[{"rthcId":"RPEP-00001","title":"Identification of two related pentapeptides from the brain with potent opiate agonist activity.","authors":"Hughes, J; Smith, T W; Kosterlitz, H W; Fothergill, L A; Morgan, B A; Morris, H R","year":1975,"journal":"Nature, 258(5536), 577-80","doi":null,"pmid":"1207728","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The researchers identified enkephalin as consisting of two related pentapeptides (five-amino-acid chains): met-enkephalin (Tyr-Gly-Gly-Phe-Met) and leu-enkephalin (Tyr-Gly-Gly-Phe-Leu). These peptides differ only in their final amino acid — methionine versus leucine. Both act as natural ligands (binding molecules) for opioid receptors in the brain, meaning they are the body's endogenous counterparts to plant-derived opiates like morphine.\n\nThe identification was confirmed by sequencing the natural peptides using the dansyl-Edman procedure and mass spectrometry, then chemically synthesizing both sequences and showing they matched the biological activity of the natural extracts.","whyItMatters":"This is one of the most important papers in neuroscience history. Before this discovery, scientists knew the brain had receptors for opiates but couldn't explain why — since plants make morphine, not humans. Finding that the brain produces its own opioid peptides explained why we have opioid receptors in the first place and launched the entire field of endogenous opioid research. It fundamentally changed our understanding of pain, addiction, mood regulation, and the brain's reward system.","specificNumbers":"","methodology":"The researchers extracted enkephalin from pig brain tissue, then used two complementary analytical techniques — the dansyl-Edman degradation procedure (which reads amino acid sequences one letter at a time) and mass spectrometry — to determine the exact amino acid sequences. They then chemically synthesized both peptides in the laboratory and compared the synthetic versions to the natural brain extracts to confirm identical structure and biological activity.","limitations":"The abstract is notably brief, as was common for Nature papers in 1975. The initial characterization was limited to identifying the sequences and confirming opioid receptor binding. The broader physiological roles of enkephalins — including their involvement in pain modulation, mood, gut function, and immune regulation — would only be elucidated in subsequent decades of research. The work used pig brain tissue, though enkephalins were later confirmed across mammalian species including humans."},{"rthcId":"RPEP-00002","title":"The delta EEG (sleep)-inducing peptide (DSIP). XI. Amino-acid analysis, sequence, synthesis and activity of the nonapeptide.","authors":"Schoenenberger, G A; Maier, P F; Tobler, H J; Wilson, K; Monnier, M","year":1978,"journal":"Pflugers Archiv : European journal of physiology, 376(2), 119-29","doi":null,"pmid":"568769","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The researchers isolated, sequenced, and synthesized the Delta Sleep-Inducing Peptide (DSIP) — a nine-amino-acid peptide (Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu) from rabbit cerebral venous blood during electrical stimulation of sleep-promoting brain regions. When the synthetic DSIP was infused into rabbit brain ventricles at 6 nmol/kg, it increased delta wave EEG activity by 35% in both the neocortex and limbic cortex compared to controls. Only the alpha-aspartyl form was active; the beta-Asp isomer was inactive. None of the 8 other tested peptides (metabolic fragments and analogs) reproduced the effect.","whyItMatters":"This 1978 paper represents the original characterization and synthesis of DSIP — the first peptide identified as a potential natural sleep-inducing molecule. It was a landmark in sleep neuroscience, suggesting that the brain produces specific peptide signals to initiate and maintain slow-wave sleep. The finding that only the exact sequence with the correct aspartyl configuration was active demonstrated remarkable molecular specificity.","specificNumbers":"9 amino acids (Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu) · 6 nmol/kg intraventricular · 35% increase in delta EEG activity · 61 rabbits total · 9 peptides tested · Only alpha-Asp form active · Double-blind design","methodology":"DSIP was isolated from extracorporeal dialysate of cerebral venous blood in rabbits during electrical stimulation of the intralaminar thalamic area (a sleep-promoting brain region). The peptide was sequenced and synthesized, along with 5 metabolic fragments, 2 analogs, and 1 related tripeptide. All 9 synthetic peptides were infused intraventricularly in rabbits under double-blind conditions. EEG from frontal neocortex and limbic archicortex was analyzed by fast-Fourier transformation.","limitations":"This is a rabbit study using direct intraventricular infusion — the peptide was injected directly into the brain, bypassing the blood-brain barrier. Whether DSIP can reach the brain through peripheral administration is a separate question. The 35% delta increase, while statistically significant, is a moderate effect. Subsequent DSIP research has had mixed reproducibility, with some groups unable to replicate sleep-inducing effects."},{"rthcId":"RPEP-00003","title":"Dynorphin-(1-13), an extraordinarily potent opioid peptide.","authors":"Goldstein, A; Tachibana, S; Lowney, L I; Hunkapiller, M; Hood, L","year":1979,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 76(12), 6666-70","doi":null,"pmid":"230519","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00004","title":"Coupling factor F1 ATPase with defective beta subunit from a mutant of Escherichia coli.","authors":"Kanazawa, H; Horiuchi, Y; Takagi, M; Ishino, Y; Futai, M","year":1980,"journal":"Journal of biochemistry, 88(3), 695-703","doi":null,"pmid":"6448252","tags":["peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"The mutant F1 ATPase (an enzyme that helps cells make energy) had only 6 to 9 units of activity per milligram of protein. That is about 10 to 15 times less than the normal version.\n\nThe mutant enzyme also broke down faster. After two weeks in the freezer at minus 80 degrees Celsius, it lost about 80% of its activity. The normal enzyme lost none.\n\nWhen researchers swapped the beta subunit from a normal enzyme into the broken one, activity jumped back up to about 20 units per milligram. That confirmed the problem was in the beta subunit alone. Peptide mapping showed just one peptide fragment differed between the mutant and normal beta subunits.","whyItMatters":"This study is one of the early demonstrations that a single peptide change in a protein subunit can dramatically alter enzyme function and stability. It helped establish the role of the beta subunit in bacterial ATP production.","specificNumbers":"","methodology":"Researchers purified the F1 ATPase enzyme from both normal and mutant E. coli bacteria. They measured its ability to break down ATP (the cell's energy currency) using both magnesium and calcium. They then took the enzyme apart into its subunits and mixed pieces from the normal and mutant versions to figure out which subunit carried the defect. Tryptic peptide mapping compared the protein fragments.","limitations":"This study used a single bacterial mutant strain. It did not test whether the findings apply to other organisms. The work is purely biochemical and has no direct link to human health or therapeutic peptides."},{"rthcId":"RPEP-00005","title":"Release of enkephalins and enkephalin-containing polypeptides from perfused beef adrenal glands.","authors":"Kilpatrick, D L; Lewis, R V; Stein, S; Udenfriend, S","year":1980,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 77(12), 7473-5","doi":null,"pmid":"6938986","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00006","title":"Effect of delta sleep inducing peptide (DSIP) and arginine vasotocin (AVT) on sleep and motor activity in the rat.","authors":"Tobler, I; Borbély, A A","year":1980,"journal":"Waking and sleeping, 4(2), 139-53","doi":null,"pmid":"7405185","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"DSIP administered systemically (40-160 nmol/kg) did not significantly reduce motor activity over 24 hours, and neither injection nor infusion of DSIP into brain ventricles (7-24 nmol) significantly increased sleep or EEG delta power. AVT injected into brain ventricles at extremely low doses (10⁻¹⁵ to 10⁻¹⁹ mol) similarly failed to enhance sleep.\n\nHowever, both peptides showed biological activity: DSIP at 160 nmol/kg reduced dark-time motor activity 1-2 days after administration, and at 80 nmol/kg it paradoxically increased activity in the first 4 hours. Both DSIP and AVT reduced delta-band EEG power when administered into the third ventricle — the opposite of what a sleep-promoting substance would do. AVT's effects at femtomolar doses were notable, suggesting biological activity at concentrations far below typical peptide drug ranges.","whyItMatters":"DSIP was originally isolated and named for its apparent ability to induce slow-wave sleep, and it became widely referenced in the peptide supplement community. This early negative study is important because it challenged the foundational claim about DSIP's sleep-promoting properties using rigorous EEG and behavioral methods. It helped establish that DSIP's effects are more complex and less specific than its name implies.","specificNumbers":"","methodology":"Rats received DSIP via systemic injection (intraperitoneal) or direct brain ventricle infusion at multiple doses. AVT was administered into brain ventricles at extremely low concentrations. Motor activity was monitored over 24 hours, and sleep architecture was assessed using EEG recordings, with particular attention to delta-band power (the signature of deep slow-wave sleep).","limitations":"This was a rat study, and sleep architecture differs significantly between rodents and humans. The sample size was not reported in the abstract. DSIP's effects on sleep may be species-specific or require specific conditions not replicated in this experimental setup. The study tested a limited range of doses and timing protocols — it's possible that different regimens might produce different results."},{"rthcId":"RPEP-00007","title":"Opioid peptides in adrenal gland.","authors":"Yang, H Y; Hexum, T; Costa, E","year":1980,"journal":"Life sciences, 27(13), 1119-25","doi":null,"pmid":"6252400","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00008","title":"A rapid and potent natriuretic response to intravenous injection of atrial myocardial extract in rats.","authors":"de Bold, A J; Borenstein, H B; Veress, A T; Sonnenberg, H","year":1981,"journal":"Life sciences, 28(1), 89-94","doi":null,"pmid":"7219045","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00009","title":"Modulation of terminal deoxynucleotidyl transferase activity by thymosin.","authors":"Hu, S K; Low, T L; Goldstein, A L","year":1981,"journal":"Molecular and cellular biochemistry, 41, 49-58","doi":null,"pmid":"7329413","tags":["thymosin-alpha-1","thymosin-beta-4","immune-function"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Thymosin peptides both increase and decrease TdT activity depending on the maturation stage, indicating they regulate multiple phases of T-cell development.","whyItMatters":"This research demonstrated that specific thymosin peptides can actively direct immune cell development at multiple stages, supporting their potential as immune-modulating therapies.","specificNumbers":"","methodology":"Researchers injected thymosin fraction 5, beta-3, and beta-4 daily into immune-suppressed mice and measured TdT activity compared to controls. In separate in vitro experiments, thymosin fraction 5 and alpha-1 were incubated with normal mouse thymus cells for 22 hours.","limitations":"This was an animal study using mice, and the in vitro system may not fully reflect the complexity of immune development in living organisms. No human data was provided."},{"rthcId":"RPEP-00010","title":"Co-release of enkephalin and catecholamines from cultured adrenal chromaffin cells.","authors":"Livett, B G; Dean, D M; Whelan, L G; Udenfriend, S; Rossier, J","year":1981,"journal":"Nature, 289(5795), 317-9","doi":null,"pmid":"7453829","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00011","title":"Acute and delayed effects of DSIP (delta sleep-inducing peptide) on human sleep behavior.","authors":"Schneider-Helmert, D; Gnirss, F; Monnier, M; Schenker, J; Schoenenberger, G A","year":1981,"journal":"International journal of clinical pharmacology, therapy, and toxicology, 19(8), 341-5","doi":null,"pmid":"6895513","tags":[],"studyType":"Double-Blind Crossover Trial","evidenceStrength":"Preliminary","keyFinding":"When DSIP (delta sleep-inducing peptide) was given intravenously to healthy volunteers, total sleep time increased by 59% within 130 minutes of the morning infusion compared to placebo. Subjects immediately reported a feeling of 'sleep pressure' after receiving the peptide.\n\nDSIP also produced delayed effects on nighttime sleep: shorter time to fall asleep, reduced stage 1 (lightest) sleep, and better overall sleep efficiency. Critically, detailed behavioral and EEG analysis showed no sedation in the traditional pharmacological sense — DSIP appeared to support natural sleep mechanisms rather than forcing unconsciousness. No psychological, physiological, or biochemical side effects were observed.","whyItMatters":"This was one of the first human studies of DSIP, a peptide originally discovered in rabbit brain dialysate. The finding that it increased sleep by 59% without causing sedation was remarkable — suggesting a fundamentally different mechanism from sleeping pills like benzodiazepines. It supported the idea that DSIP enhances natural sleep architecture rather than drug-induced unconsciousness, making it a conceptual predecessor to modern sleep research focused on restoring physiological sleep patterns.","specificNumbers":"n=6 · 59% increase in total sleep time (median) · 25 nmol/kg IV dose · 130-minute observation window · Reduced sleep onset latency at night · Reduced stage 1 sleep · Improved sleep efficiency · No side effects observed","methodology":"Six healthy volunteers (4 male, 2 female) received either DSIP (25 nmol/kg) or placebo via slow intravenous infusion in the morning in a double-blind crossover design. Subjects underwent extensive psychophysiological monitoring including sleep staging, EEG analysis, and behavioral assessment during the immediate post-infusion period and the subsequent night's sleep.","limitations":"Extremely small sample of only 6 volunteers limits statistical power and generalizability. The 1981 study predates modern sleep research standards and polysomnographic technology. IV administration is impractical for clinical use. No dose-ranging was performed. The 'median' 59% increase in such a small sample may be heavily influenced by individual variation. Long-term safety and efficacy were not assessed."},{"rthcId":"RPEP-00012","title":"The influence of synthetic DSIP (delta-sleep-inducing-peptide) on disturbed human sleep.","authors":"Schneider-Helmert, D; Schoenenberger, G A","year":1981,"journal":"Experientia, 37(9), 913-7","doi":null,"pmid":"7028502","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00013","title":"Mammalian neuronal actions of FMRFamide and the structurally related opioid Met-enkephalin-Arg6-Phe7.","authors":"Gayton, R J","year":1982,"journal":"Nature, 298(5871), 275-6","doi":null,"pmid":"6283381","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00014","title":"Adrenal medullary enkephalin-like peptides may mediate opioid stress analgesia.","authors":"Lewis, J W; Tordoff, M G; Sherman, J E; Liebeskind, J C","year":1982,"journal":"Science (New York, N.Y.), 217(4559), 557-9","doi":null,"pmid":"7089582","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Different patterns of foot shock in rats activated two distinct pain-suppression mechanisms: opioid and non-opioid stress analgesia. Adrenal demedullation (removing the adrenal medulla) and adrenal denervation reduced opioid stress analgesia but did not affect non-opioid stress analgesia. Reserpine, which is known to increase concentrations of adrenal medullary enkephalin-like peptides, potentiated the opioid form of stress analgesia.\n\nThese findings established that adrenal enkephalins — endogenous opioid peptides produced outside the brain — are key mediators of opioid stress-induced pain relief.","whyItMatters":"This study helped establish that the body has multiple built-in pain-control systems, and that enkephalin peptides from the adrenal glands play a specific role in one of them. Understanding how endogenous opioid peptides mediate stress analgesia has been fundamental to pain research and has informed our understanding of how the body manages pain without external drugs.","specificNumbers":"","methodology":"Rats were subjected to different patterns of foot shock to induce stress analgesia. Some rats underwent adrenal demedullation (surgical removal of the adrenal medulla) or adrenal denervation to eliminate adrenal enkephalin release. Others were treated with reserpine to increase adrenal enkephalin levels. Pain sensitivity was then measured to determine whether opioid or non-opioid analgesia was affected.","limitations":"The study used foot shock in rats, which is an artificial stressor that may not fully represent human stress experiences. The abstract does not report specific sample sizes or statistical details. As a 1982 study, the techniques available were more limited than modern approaches to measuring peptide release and receptor activity."},{"rthcId":"RPEP-00015","title":"Tetrahymena histone H2B. Complete amino acid sequence.","authors":"Nomoto, M; Hayashi, H; Iwai, K","year":1982,"journal":"Journal of biochemistry, 91(3), 897-904","doi":null,"pmid":"6804458","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00016","title":"Successful treatment of withdrawal symptoms with delta sleep-inducing peptide, a neuropeptide with potential agonistic activity on opiate receptors.","authors":"Dick, P; Grandjean, M E; Tissot, R","year":1983,"journal":"Neuropsychobiology, 10(4), 205-8","doi":null,"pmid":"6328354","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00017","title":"Alloreactivity. I. Effects of age and thymic hormone treatment on cell-mediated immunity in C57B1/6NNia mice.","authors":"Ghanta, V K; Noble, P J; Brown, M E; Cox, P J; Hiramoto, N S; Hiramoto, R N","year":1983,"journal":"Mechanisms of ageing and development, 22(3-4), 309-19","doi":null,"pmid":"6415352","tags":["thymosin-alpha-1","immune-function","anti-aging"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Mice lost immune killing power as they aged. By 24 months (equivalent to roughly 70+ human years), their spleen cells were much weaker at destroying tumor cells compared to 1-month-old mice.\n\nFour thymic hormones were tested: FTS (serum thymic factor), TP5 (a fragment of thymopoietin), TM4 (a synthetic version of TP5), and thymosin fraction V. Each worked differently depending on the age of the mouse and the dose used.\n\nThe most striking result: TM4 at a very low dose (1 nanogram) actually suppressed immune killing in young mice but significantly boosted it in 12- and 24-month-old mice. FTS and TP5 partially restored killing ability in old mice. Thymosin fraction V had modest and inconsistent effects.","whyItMatters":"This study showed that age-related immune decline is not permanent. Thymic hormones can partially reverse it, at least in mice. The finding that different hormones work differently at different ages suggests immune restoration might need to be tailored to the patient's age.","specificNumbers":"","methodology":"Researchers used C57B1/6NNia mice at 1, 12, and 24 months of age. Each age group received one of four thymic hormone preparations at various doses. After treatment, spleen cells were tested for their ability to kill P815 mastocytoma (tumor) cells. This is a standard immune function test called a cytotoxicity assay.","limitations":"This was a mouse study with small group sizes. The effects were inconsistent across hormones and doses. The study measured only one type of immune function (tumor cell killing) and did not track whether treated mice actually lived longer or resisted infections better."},{"rthcId":"RPEP-00018","title":"Vasoactive intestinal peptide causes bronchodilatation and protects against histamine-induced bronchoconstriction in asthmatic subjects.","authors":"Morice, A; Unwin, R J; Sever, P S","year":1983,"journal":"Lancet (London, England), 2(8361), 1225-7","doi":null,"pmid":"6139572","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Intravenous VIP caused significant bronchodilation in all seven asthmatic volunteers and protected against histamine-induced bronchoconstriction in every subject. The dose was 6 pmol/kg/min infused over 15 minutes. Side effects included tachycardia (rapid heart rate) and cutaneous flushing during the infusion.","whyItMatters":"This was one of the first human studies demonstrating that VIP — a naturally occurring peptide — could open airways in asthma patients and block histamine-triggered airway narrowing. Published in The Lancet in 1983, it established VIP as a potential natural bronchodilator in humans and suggested an entirely new peptide-based approach to asthma treatment.","specificNumbers":"n=7 asthmatic volunteers · 6 pmol/kg/min for 15 min · Bronchodilation in all subjects · Protection against histamine-induced bronchoconstriction in all subjects","methodology":"Double-blind study in seven adult asthmatic volunteers. VIP was administered intravenously at 6 pmol/kg/min for 15 minutes. Bronchodilation was measured (likely by forced expiratory volume), and subjects were also challenged with histamine to test whether VIP could protect against bronchoconstriction.","limitations":"Very small sample size (only 7 subjects). Intravenous delivery caused systemic side effects (tachycardia, flushing), making this route impractical for routine asthma treatment. The study did not test inhaled VIP, which would be the clinically relevant delivery method. Short duration — only a single 15-minute infusion was tested."},{"rthcId":"RPEP-00019","title":"Biliary excretion of procollagen type III peptide in healthy humans and in patients with alcoholic cirrhosis of the liver.","authors":"Raedsch, R; Stiehl, A; Sieg, A; Walker, S; Kommerell, B","year":1983,"journal":"Gastroenterology, 85(6), 1265-70","doi":null,"pmid":"6628925","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00020","title":"Anglerfish preprosomatostatin II is processed to somatostatin-28 and contains hydroxylysine at residue 23.","authors":"Andrews, P C; Hawke, D; Shively, J E; Dixon, J E","year":1984,"journal":"The Journal of biological chemistry, 259(24), 15021-4","doi":null,"pmid":"6150931","tags":["neuropeptides","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Two versions of somatostatin-28 were isolated from anglerfish tissue. Both came from the same gene, but one had a modified amino acid: 5-hydroxylysine at position 23.\n\nMass spectrometry confirmed the two forms had molecular weights of 3,220 (hydroxylated) and 3,204 (non-hydroxylated). The 16-unit difference matches exactly what adding one oxygen atom would do.\n\nThis was the first documented case of a hydroxylated peptide hormone. Before this, hydroxylysine was known almost exclusively from collagen (the protein that gives skin and bones their structure).","whyItMatters":"This changed what scientists thought about peptide hormone modifications. Finding hydroxylysine in a hormone meant that post-translational modifications (chemical changes made after a protein is built) are more widespread than previously believed. It opened questions about whether similar modifications exist in human peptide hormones.","specificNumbers":"","methodology":"Researchers isolated peptide fractions from anglerfish pancreatic islets. They identified the two somatostatin-28 forms using amino acid sequence analysis, gas chromatography/mass spectrometry for the hydroxylysine, and fast-atom bombardment mass spectrometry for molecular weight confirmation. Proteolytic fragment analysis pinpointed the modification to position 23.","limitations":"This study examined only anglerfish somatostatin. It did not determine whether the hydroxylation affects the peptide's biological activity. It is unknown whether mammalian somatostatins carry the same modification."},{"rthcId":"RPEP-00021","title":"Delta-sleep-inducing peptide (DSIP): a review.","authors":"Graf, M V; Kastin, A J","year":1984,"journal":"Neuroscience and biobehavioral reviews, 8(1), 83-93","doi":null,"pmid":"6145137","tags":[],"studyType":"Review","evidenceStrength":"preliminary","keyFinding":"Delta-sleep-inducing peptide (DSIP) is a nonapeptide (nine amino acids, molecular weight 849) that primarily induces delta sleep (deep, slow-wave sleep) in rabbits, rats, mice, and humans, while in cats it more strongly affects REM sleep. The peptide was one of only two purified and characterized sleep-inducing peptides at the time of this review.\n\nDSIP shows a U-shaped dose-response curve — meaning both too little and too much are less effective, with an optimal middle dose. DSIP-like material was found throughout the brain and peripheral organs via immunoassays and was detected in the blood plasma of several mammalian species. Beyond sleep, DSIP affects neurotransmitter levels, circadian rhythms, locomotor activity, hormone levels, psychological performance, and even modifies the effects of neuropharmacological drugs including withdrawal symptoms.","whyItMatters":"DSIP was among the first peptides identified as a natural sleep factor, supporting the century-old hypothesis that humoral (blood-borne) factors regulate sleep. Its discovery helped establish the concept that the brain uses peptide signaling to control sleep architecture — a field that later expanded dramatically with the discovery of orexin/hypocretin. DSIP's diverse effects beyond sleep (circadian rhythm, drug withdrawal, hormones) also foreshadowed the modern understanding that neuropeptides rarely have just one function.","specificNumbers":"9 amino acids · MW 849 · Induces delta (deep) sleep · U-shaped dose-response · Found in brain + peripheral organs + plasma · Effects on sleep, neurotransmitters, circadian rhythm, hormones, drug withdrawal","methodology":"Comprehensive literature review published in Neuroscience and Biobehavioral Reviews, covering DSIP's discovery, purification, characterization, distribution in the body (via radioimmunoassay and immunohistochemistry), sleep-inducing properties across multiple species, and broader neurological and physiological effects.","limitations":"Published in 1984, so reflects early-stage understanding of this peptide. Subsequent research has raised questions about DSIP's specificity as a sleep-inducing agent and whether it functions as a true endogenous sleep factor. The U-shaped dose-response curve makes it difficult to study and interpret. Reproducibility of sleep-inducing effects has been debated in the subsequent literature."},{"rthcId":"RPEP-00022","title":"Therapeutic effects of delta-sleep-inducing peptide (DSIP) in patients with chronic, pronounced pain episodes. A clinical pilot study.","authors":"Larbig, W; Gerber, W D; Kluck, M; Schoenenberger, G A","year":1984,"journal":"European neurology, 23(5), 372-85","doi":null,"pmid":"6548970","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00023","title":"Diagnostic value of serum procollagen peptide measurements in alcoholic liver disease.","authors":"Savolainen, E R; Goldberg, B; Leo, M A; Velez, M; Lieber, C S","year":1984,"journal":"Alcoholism, clinical and experimental research, 8(4), 384-9","doi":null,"pmid":"6385761","tags":[],"studyType":"diagnostic","evidenceStrength":"moderate","keyFinding":"Serum procollagen type III aminoterminal peptide was elevated in 90% of patients with alcoholic hepatitis and cirrhosis, while type I carboxyterminal peptide was elevated in 60–80% of these patients. Both peptides were significantly higher in alcoholic hepatitis and cirrhosis compared to fatty liver alone (type III: p<0.001; type I: p<0.005).\n\nHowever, these tests could not reliably distinguish simple fatty liver from fatty liver with early fibrosis. The highest peptide levels were found in patients with alcoholic hepatitis who also had numerous Mallory bodies, suggesting the measurements partly reflect hepatic inflammation rather than fibrosis alone.","whyItMatters":"Detecting how far alcoholic liver disease has progressed is critical for treatment decisions. This study showed that measuring procollagen peptides in blood could help identify severe alcoholic hepatitis — a potentially life-threatening condition — without requiring a liver biopsy. While not perfect, these peptide biomarkers offered a non-invasive window into liver collagen production and inflammation.","specificNumbers":"n=74 · 90% elevated type III peptide in hepatitis/cirrhosis · 60–80% elevated type I peptide · p<0.001 type III fatty liver vs hepatitis/cirrhosis · p<0.005 type I fatty liver vs hepatitis","methodology":"The researchers measured two procollagen peptide types (type I carboxyterminal and type III aminoterminal) in blood samples from 60 patients with alcoholic liver disease and 14 with non-alcoholic liver disease. They compared peptide levels across disease stages: fatty liver, alcoholic hepatitis, and cirrhosis, and correlated values with liver biopsy findings including fibrosis grade and inflammation.","limitations":"There was considerable overlap in peptide values between disease groups, limiting the tests' ability to classify individual patients. The study could not distinguish simple fatty liver from fatty liver with early fibrosis. The sample size of 74 patients was relatively small, and the study predates modern imaging and biomarker techniques."},{"rthcId":"RPEP-00024","title":"Modulation of natural killer activity by thymosin alpha 1 and interferon.","authors":"Favalli, C; Jezzi, T; Mastino, A; Rinaldi-Garaci, C; Riccardi, C; Garaci, E","year":1985,"journal":"Cancer immunology, immunotherapy : CII, 20(3), 189-92","doi":null,"pmid":"3851698","tags":["thymosin-alpha-1","immune-function","cancer"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Natural killer (NK) cells are immune cells that destroy virus-infected and cancer cells without needing prior training. Cyclophosphamide (CY), a chemotherapy drug, wiped out NK cell activity in mice.\n\nInterferon alone (30,000 units per mouse) strongly boosted NK cells in healthy mice. But in CY-suppressed mice, interferon by itself did nothing.\n\nThe combination worked: thymosin alpha 1 (200 micrograms/kg) given daily for 4 days, followed by a single interferon injection 24 hours before testing, fully restored NK cell activity in the immunosuppressed mice. Thymosin alpha 1 also accelerated NK cell recovery in mice that received bone marrow transplants.","whyItMatters":"This study showed thymosin alpha 1 can prime the immune system so that interferon becomes effective again. For patients on chemotherapy who lose immune function, this combination could theoretically help restore cancer-fighting NK cells. The synergy between the two agents was the key finding.","specificNumbers":"","methodology":"Researchers used mice suppressed with cyclophosphamide and bone marrow transplant chimeras. They tested thymosin alpha 1 (200 micrograms/kg daily for 4 days) combined with a single interferon injection (30,000 units). NK cell activity was measured using standard cytotoxicity assays. Tested in mice, not people.","limitations":"This was a mouse study with small numbers. The study measured NK cell activity at a single time point and did not track whether the restored NK cells actually prevented tumor growth or improved survival. The doses may not translate directly to humans."},{"rthcId":"RPEP-00025","title":"Defensins. Natural peptide antibiotics of human neutrophils.","authors":"Ganz, T; Selsted, M E; Szklarek, D; Harwig, S S; Daher, K; Bainton, D F; Lehrer, R I","year":1985,"journal":"The Journal of clinical investigation, 76(4), 1427-35","doi":null,"pmid":"2997278","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00026","title":"Evidence that thymosins and other biologic response modifiers can function as neuroactive immunotransmitters.","authors":"Hall, N R; McGillis, J P; Spangelo, B L; Goldstein, A L","year":1985,"journal":"Journal of immunology (Baltimore, Md. : 1950), 135(2 Suppl), 806s-811s","doi":null,"pmid":"2861235","tags":["thymosin-alpha-1","thymosin-beta-4","neuropeptides","immune-function"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"The paper argued that certain molecules made by immune cells can send signals directly to the brain. The authors named these 'immunotransmitters,' a new term for molecules that carry information from the immune system to the central nervous system (CNS).\n\nExamples include thymosin alpha 1 and thymosin beta 4 (peptides from the thymus gland), as well as ACTH (a stress hormone), TSH (thyroid hormone), and beta-endorphin (a natural painkiller) produced by lymphocytes (white blood cells).\n\nThe review presented evidence that thymosin peptides can alter the hypothalamic-pituitary-adrenal (HPA) axis, which is the brain's master hormone control system. They also appeared to affect the gonadal (reproductive hormone) axis.","whyItMatters":"This paper helped establish the concept of neuroimmunology, the idea that the immune system and nervous system are deeply interconnected. It moved beyond the old view that these systems operate independently. The 'immunotransmitter' concept influenced decades of research.","specificNumbers":"","methodology":"This is a narrative review. The authors collected evidence from multiple studies showing immune-to-brain communication. No new experiments were conducted.","limitations":"This is a review paper, not original research. The concept of immunotransmitters was speculative at the time and based on limited experimental evidence. Many of the proposed mechanisms had not yet been confirmed."},{"rthcId":"RPEP-00027","title":"Parathymosin alpha: a peptide from rat tissues with structural homology to prothymosin alpha.","authors":"Haritos, A A; Salvin, S B; Blacher, R; Stein, S; Horecker, B L","year":1985,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 82(4), 1050-3","doi":null,"pmid":"3856246","tags":["thymosin-alpha-1","immune-function","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Parathymosin alpha is a newly discovered peptide of about 105 amino acid residues, isolated from rat thymus tissue. The first 30 amino acids of its sequence showed 43% structural identity with thymosin alpha 1 and prothymosin alpha.\n\nThe structural overlap did not include residues 2 through 9 of thymosin alpha 1. This explained why antibodies targeting that region of thymosin alpha 1 did not recognize parathymosin alpha.\n\nFunctionally, parathymosin alpha appeared to regulate prothymosin alpha's ability to protect sensitive mice from Candida albicans (a common fungal infection). This suggests it acts as a modulator of immune protection rather than a direct immune booster.","whyItMatters":"Discovering a new thymic peptide that regulates another thymic peptide revealed a more complex thymic hormone system than previously thought. It showed the thymus does not just produce one or two hormones but a family of interacting peptides that fine-tune immune responses.","specificNumbers":"","methodology":"Researchers purified parathymosin alpha from rat thymus tissue and determined the sequence of its first 30 amino acids. They tested antibody cross-reactivity with thymosin alpha 1. They also tested its effect on prothymosin alpha-mediated protection against Candida albicans infection in mice.","limitations":"Only the first 30 of approximately 105 amino acids were sequenced. The full function of parathymosin alpha remains unknown. The Candida protection experiment was limited and did not fully characterize the mechanism."},{"rthcId":"RPEP-00028","title":"Opioid activities of human beta-casomorphins.","authors":"Koch, G; Wiedemann, K; Teschemacher, H","year":1985,"journal":"Naunyn-Schmiedeberg's archives of pharmacology, 331(4), 351-4","doi":null,"pmid":"3005882","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00029","title":"High affinity receptors for bombesin/GRP-like peptides on human small cell lung cancer.","authors":"Moody, T W; Carney, D N; Cuttitta, F; Quattrocchi, K; Minna, J D","year":1985,"journal":"Life sciences, 37(2), 105-13","doi":null,"pmid":"2409423","tags":[],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Human small cell lung cancer (SCLC) cells express high-affinity receptors for bombesin/GRP (gastrin-releasing peptide) — with about 2,000 binding sites per cell and a binding affinity (Kd) of 0.5 nM. The receptor binding was specific: bombesin and the structurally related peptide GRP competed for binding, but unrelated peptides like substance P and vasopressin did not.\n\nCritically, since SCLC cells both produce bombesin/GRP-like peptides AND express receptors for them, these peptides likely function as autocrine growth factors — the cancer cells stimulate their own growth through a self-reinforcing peptide signaling loop. The receptor was identified as a 78,000-dalton (78 kDa) polypeptide.","whyItMatters":"This foundational study established that bombesin/GRP acts as an autocrine growth signal in small cell lung cancer — meaning the tumor stimulates its own growth through peptide signaling. This discovery opened an entirely new therapeutic approach: blocking the bombesin/GRP receptor to cut off the tumor's self-stimulation. It also made bombesin receptors a target for peptide-based cancer diagnostics and drug delivery, a concept that has since expanded to multiple cancer types.","specificNumbers":"Kd = 0.5 nM binding affinity · ~2,000 receptors per cell · 78 kDa receptor protein · Specific for bombesin/GRP (not substance P or vasopressin) · Binding reversible and saturable","methodology":"Researchers used radiolabeled bombesin analog ((125I-Tyr4)bombesin) to characterize receptor binding on two SCLC cell lines (NCI-H446 and NCI-H345). Binding kinetics, specificity, and competition with related and unrelated peptides were determined. The receptor protein was identified by affinity purification using bombesin and GRP resins, followed by SDS-PAGE gel electrophoresis.","limitations":"This is an in vitro study using cultured cell lines, which may not fully represent the receptor expression and signaling dynamics of tumors in living patients. Only two SCLC cell lines were characterized. The autocrine growth hypothesis, while strongly supported by the data, was not directly tested with growth inhibition experiments in this paper. The study predates modern receptor cloning and molecular biology techniques."},{"rthcId":"RPEP-00030","title":"Type III procollagen peptide and PZ-peptidase serum levels in pre-cirrhotic liver diseases.","authors":"Morelli, A; Vedovelli, A; Fiorucci, S; Angelini, G P; Fini, C; Palmerini, C A; Floridi, A","year":1985,"journal":"Clinica chimica acta; international journal of clinical chemistry, 148(2), 87-95","doi":null,"pmid":"3888456","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00031","title":"Intestinal lymphangiectasia and thymic hypoplasia.","authors":"Sorensen, R U; Halpin, T C; Abramowsky, C R; Hornick, D L; Miller, K M; Naylor, P; Incefy, G S","year":1985,"journal":"Clinical and experimental immunology, 59(1), 217-26","doi":null,"pmid":"3971596","tags":["thymosin-alpha-1","immune-function","gut-healing"],"studyType":"case-report","evidenceStrength":"preliminary","keyFinding":"The patient had primary intestinal lymphangiectasia (a condition where lymph vessels in the gut leak fluid, protein, and immune cells). Biopsies confirmed the diagnosis in her intestines, lungs, and lymph nodes. Lymphocytes were literally leaking out through her gut, confirmed by finding them in her stool.\n\nHer thymus gland was essentially absent. A biopsy showed no thymic tissue. Blood tests showed very low or absent thymulin and thymosin alpha 1. She had a selective loss of T-cells, especially CD4+ helper T-cells.\n\nDaily thymosin fraction 5 treatment produced a brief clinical improvement. But switching to weekly injections could not sustain it. Lymphocyte numbers never increased during treatment. The authors concluded that when the body loses T-cells faster than it can replace them, even thymic hormones cannot keep up without a functioning thymus.","whyItMatters":"This case showed a fundamental limit of thymic hormone therapy. Without a functioning thymus to produce new T-cells, thymic peptides alone cannot overcome ongoing lymphocyte loss. It highlighted that T-cell output and thymic structure are codependent.","specificNumbers":"","methodology":"Single patient case report. Immune workup included lymphocyte subpopulation analysis, proliferative responses to mitogens, NK cell function, and serum thymic hormone levels. Treatment was thymosin fraction 5, first daily then weekly. Biopsies of intestine, lung, lymph node, and thymus were performed.","limitations":"This is a single case report. One patient's response cannot predict how others with similar conditions would respond. The thymosin dosing schedule was changed during treatment, making it hard to separate dose effects from disease progression."},{"rthcId":"RPEP-00032","title":"Modulation of thymosin beta 4 by estrogen.","authors":"Suh, B Y; Naylor, P H; Goldstein, A L; Rebar, R W","year":1985,"journal":"American journal of obstetrics and gynecology, 151(4), 544-9","doi":null,"pmid":"2983555","tags":["thymosin-beta-4","immune-function","hormone-optimization","fertility"],"studyType":"cross-sectional","evidenceStrength":"preliminary","keyFinding":"Normal thymosin alpha 1 levels were similar across all groups of women tested, regardless of their hormonal status. This peptide appears unaffected by estrogen.\n\nThymosin beta 4 told a different story. Castrated women not receiving estrogen had reduced levels. Postmenopausal women on chronic estrogen therapy had even lower thymosin beta 4. Castrated women on estrogen also showed decreased levels.\n\nNormal women in the early follicular phase (low estrogen point of the menstrual cycle), women with premature ovarian failure, and postmenopausal women not on estrogen all had similar thymosin beta 4 levels. But the premature ovarian failure and postmenopausal groups showed wide variation, suggesting these are not uniform populations.","whyItMatters":"This showed that sex hormones specifically regulate certain thymic peptides. Since thymosin beta 4 is involved in immune regulation, wound healing, and inflammation, estrogen's ability to lower its levels could partly explain sex differences in immune function and autoimmune disease rates.","specificNumbers":"","methodology":"Cross-sectional study of 87 women. Blood samples were taken in the morning. Thymosin alpha 1 and beta 4 were measured by radioimmunoassay in the same samples. Women were grouped by hormonal status: normal cycling, premature ovarian failure, postmenopausal (with and without estrogen), castrated (with and without estrogen), and gonadal dysgenesis.","limitations":"This was an observational cross-sectional study. It cannot prove estrogen causes the thymosin beta 4 decrease, only that the two are linked. The sample groups were small, and the wide variability in some groups makes conclusions uncertain. The mechanism by which estrogen affects thymosin beta 4 was not explored."},{"rthcId":"RPEP-00033","title":"Thymosin alpha 1-induced modulation of cellular responses and functional T-cell subsets in mice with experimental autoimmune thyroiditis.","authors":"Tomazic, V J; Novotny, E A; Ordonez, J V","year":1985,"journal":"Cellular immunology, 93(2), 340-9","doi":null,"pmid":"3873993","tags":["thymosin-alpha-1","immune-function","inflammation"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Thymosin alpha 1 (Ta-1) had strikingly different effects depending on the mouse strain. In B10.D2 mice (resistant to autoimmune thyroiditis), Ta-1 treatment between the two antigen injections actually increased thyroid inflammation. In B10.Br mice (naturally susceptible), Ta-1 suppressed the disease.\n\nTiming mattered. Early treatment (first 2 weeks) suppressed disease in the susceptible strain but worsened it in the resistant strain. Later treatment (weeks 3-4) had similar patterns.\n\nDifferent doses affected different T-cell subsets. The 0.01 microgram dose lowered Lyt-2+3+ cells (a type of immune cell) in resistant mice. The 0.001 microgram dose raised Lyt-1+ cells in the same strain. Each dose shifted the immune balance differently, which explains the opposing disease outcomes.","whyItMatters":"This study revealed that thymosin alpha 1 is not simply an immune booster. It is an immune modulator that can push the system in either direction depending on the genetic background and disease state. This has important implications for anyone considering thymic peptides for autoimmune conditions.","specificNumbers":"","methodology":"Two congenic mouse strains (B10.Br and B10.D2) were given experimental autoimmune thyroiditis via thyroglobulin injection. Thymosin alpha 1 was given as 5 or 10 daily subcutaneous injections at doses from 0.0001 to 0.1 microgram. Disease was measured by thyroid lymphocyte infiltration and anti-thyroglobulin antibody levels. T-cell subsets were measured in spleens at 2 weeks.","limitations":"This was a mouse study using two specific inbred strains. The complex dose-timing-strain interactions make it hard to predict what would happen in humans. The autoimmune thyroiditis was artificially induced, not spontaneous. Small group sizes are likely given the many experimental conditions."},{"rthcId":"RPEP-00034","title":"In vitro immune modulation by thymosin alpha 1 in patients with head and neck squamous cell carcinoma.","authors":"Wolf, G T; Peterson, K A; Lovett, E J","year":1985,"journal":"Head & neck surgery, 7(5), 350-6","doi":null,"pmid":"3879957","tags":["thymosin-alpha-1","immune-function","cancer"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Leukocyte migration inhibition (LMI), a measure of how well immune cells respond to signals, was impaired in 24 head and neck cancer patients compared to healthy people.\n\nAdding thymosin alpha 1 to the lab dish improved LMI in the cancer patients' cells. The improvement appeared independent of T-cell subset levels, meaning thymosin alpha 1 was enhancing the function of existing cells rather than changing which cells were present.\n\nAn interesting secondary finding: patients whose LMI was still normal had lower levels of suppressor/cytotoxic T-cells than both healthy people and patients with impaired LMI. This suggests that suppressor cells may contribute to the immune dysfunction in these cancers.","whyItMatters":"Head and neck cancer patients often have weakened immune systems, which may limit their ability to fight the tumor. This study showed thymosin alpha 1 can restore at least one measure of immune function in these patients' cells. It provided rationale for clinical trials of thymosin alpha 1 in cancer.","specificNumbers":"","methodology":"In vitro study using blood from 24 previously untreated head and neck squamous cell carcinoma patients. Leukocyte migration inhibition was measured in response to phytohemagglutinin (a plant protein that stimulates immune cells). Thymosin alpha 1 was added to the cultures to test whether it could improve the impaired responses. T-lymphocyte subpopulations were also measured.","limitations":"This was an in vitro study. Improving cell function in a dish does not guarantee the same effect in a living patient. The study was small (24 patients) and did not test whether thymosin alpha 1 treatment would actually help patients fight their cancers or live longer."},{"rthcId":"RPEP-00035","title":"Vasoactive intestinal peptide as a bronchodilator in severe asthma.","authors":"Morice, A H; Sever, P S","year":1986,"journal":"Peptides, 7 Suppl 1, 279-80","doi":null,"pmid":"3529052","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00036","title":"Thymosin alpha 1 and thymosin beta 4 in serum: comparison of normal, cord, homosexual and AIDS serum.","authors":"Naylor, P H; Friedman-Kien, A; Hersh, E; Erdos, M; Goldstein, A L","year":1986,"journal":"International journal of immunopharmacology, 8(7), 667-76","doi":null,"pmid":"3781707","tags":["thymosin-alpha-1","thymosin-beta-4","immune-function","infection"],"studyType":"cross-sectional","evidenceStrength":"preliminary","keyFinding":"Normal thymosin alpha 1 levels: 670 ± 163 pg/mL for males and 652 ± 162 pg/mL for females. Normal thymosin beta 4 levels: 974 ± 400 ng/mL for males and 889 ± 345 ng/mL for females. Note that beta 4 levels are about 1,000 times higher than alpha 1.\n\nIn AIDS patients, 57% had elevated thymosin alpha 1 and 48% had elevated thymosin beta 4. But there was no correlation between the two peptides' levels in any group, including healthy controls.\n\nPeople with AIDS-related immune dysfunction (not full AIDS) showed a different pattern: 54% had elevated thymosin alpha 1 but only 15% had elevated thymosin beta 4. This suggests thymosin alpha 1 rises earlier in the disease process.","whyItMatters":"This was one of the first studies to establish normal reference ranges for thymosin alpha 1 and beta 4. It also showed these peptides are independently regulated and respond differently to immune crisis. The finding that thymosin alpha 1 rises first in AIDS-related immune dysfunction suggested it could serve as an early biomarker.","specificNumbers":"","methodology":"Cross-sectional study using radioimmunoassay to measure both peptides in the same serum samples. Groups included healthy men and women, neonates (cord blood), homosexual men, and AIDS patients. The distinction between AIDS and AIDS-related immune dysfunction was made clinically.","limitations":"Cross-sectional design cannot determine whether elevated thymosins cause, result from, or merely correlate with AIDS. Sample sizes for subgroups were not clearly specified. The study used 1986-era AIDS definitions, which differ from current diagnostic criteria."},{"rthcId":"RPEP-00037","title":"Modulation of interleukin 2 receptor expression on normal human lymphocytes by thymic hormones.","authors":"Sztein, M B; Serrate, S A; Goldstein, A L","year":1986,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 83(16), 6107-11","doi":null,"pmid":"3090550","tags":["thymosin-alpha-1","immune-function","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Thymosin fraction 5 (TF5), a mix of thymic peptides, significantly increased both the percentage of human lymphocytes expressing IL-2 receptors (IL-2R) and the density of receptors on each cell. This happened after the cells were stimulated with PHA (a plant protein that activates immune cells).\n\nSynthetic thymosin alpha 1 alone produced the same effect, identifying it as the active ingredient in TF5.\n\nThe effect was direct. When researchers used cyclosporin A (a drug that blocks IL-2 production), TF5 still increased IL-2R expression. This means thymosin works by directly putting more receptors on cells, not by making more IL-2. More receptors led to stronger cell multiplication.","whyItMatters":"IL-2 receptors are the gatekeepers of immune cell multiplication. Without enough receptors, immune cells cannot respond to growth signals. This study showed thymosin alpha 1 directly upregulates these receptors, explaining how it boosts immunity. This mechanism is relevant to AIDS (where IL-2R expression is low) and aging.","specificNumbers":"","methodology":"In vitro study using human blood lymphocytes. Cells were stimulated with PHA or OKT3 monoclonal antibody. IL-2 receptor expression was measured by flow cytometry. Thymosin fraction 5 and synthetic thymosin alpha 1 were tested. Cyclosporin A was used to confirm the effect was independent of IL-2 production.","limitations":"In vitro study using cells from presumably healthy donors. The effect in cells from immunocompromised patients may differ. The study did not test whether this receptor increase translates to better immune function in living people."},{"rthcId":"RPEP-00038","title":"Evaluation of hepatic fibrosis by serum proline and amino-terminal type III procollagen peptide levels in alcoholic patients.","authors":"Tanaka, Y; Minato, Y; Hasumura, Y; Takeuchi, J","year":1986,"journal":"Digestive diseases and sciences, 31(7), 712-7","doi":null,"pmid":"3720468","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Serum amino-terminal type III procollagen peptide levels showed a strong positive correlation with the degree of liver fibrosis (r = 0.733, p < 0.001) in patients with alcoholic liver disease. In contrast, serum proline levels and standard liver function tests failed to correlate significantly with the actual extent of fibrotic tissue measured by morphometric analysis of liver biopsies.","whyItMatters":"Detecting liver fibrosis early in alcoholic liver disease is critical for preventing progression to cirrhosis. Standard blood tests often miss fibrosis. This study identified a peptide biomarker — amino-terminal type III procollagen peptide — that tracks closely with the actual amount of scar tissue in the liver, offering a potential non-invasive way to monitor disease severity.","specificNumbers":"r = 0.733, p < 0.001","methodology":"Cross-sectional study comparing serum proline and amino-terminal type III procollagen peptide levels against liver biopsy morphometric analysis in 31 patients with alcoholic liver disease and 15 healthy controls.","limitations":"Small sample size of 31 patients limits generalizability. The cross-sectional design cannot establish whether peptide levels change over time with disease progression. The study is from 1986 and newer fibrosis markers have since been developed."},{"rthcId":"RPEP-00039","title":"Serum procollagen type III peptide as a marker of hepatic fibrogenesis in alcoholic hepatitis.","authors":"Torres-Salinas, M; Parés, A; Caballería, J; Jiménez, W; Heredia, D; Bruguera, M; Rodés, J","year":1986,"journal":"Gastroenterology, 90(5 Pt 1), 1241-6","doi":null,"pmid":"3007261","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00040","title":"Expression of opioid peptides in tumors.","authors":"Bostwick, D G; Null, W E; Holmes, D; Weber, E; Barchas, J D; Bensch, K G","year":1987,"journal":"The New England journal of medicine, 317(23), 1439-43","doi":null,"pmid":"2891033","tags":["opioid-peptides","cancer"],"studyType":"cross-sectional","evidenceStrength":"moderate","keyFinding":"Using a \"pan-opioid\" antibody that detects all opioid peptides, researchers screened 108 tumors. Every adrenal pheochromocytoma (15 of 15), thyroid medullary carcinoma (6 of 6), and pituitary adenoma (5 of 5) stained positive for opioid peptides.\n\nMost parathyroid adenomas (8 of 9), pancreatic islet-cell tumors (7 of 10), and carcinoid tumors (18 of 26) also stained positive.\n\nZero non-neuroendocrine tumors showed opioid staining. Lung small-cell carcinomas, skin Merkel-cell tumors, and neuroblastomas were all negative.\n\nThe same opioid peptides were found in normal versions of these tissues (adrenal medulla, pancreatic islets, pituitary), suggesting the tumors simply overproduce a normal cellular product.","whyItMatters":"This study established opioid peptides as reliable markers for neuroendocrine differentiation in tumors. For pathologists trying to classify unclear tumors, opioid peptide staining could help identify their origin. Published in the New England Journal of Medicine, this was a high-impact finding.","specificNumbers":"","methodology":"Immunohistochemistry study of 108 tumors using avidin-biotin immunoperoxidase technique. A monoclonal pan-opioid antibody (3-E7) detected the common opioid sequence Tyr-Gly-Gly-Phe. Polyclonal antibodies identified specific opioid subtypes: alpha-endorphin, met-enkephalin, and dynorphin B.","limitations":"This was a descriptive study. It did not determine whether opioid peptide production by tumors has any functional consequences (like pain modulation or hormone effects). The sample sizes for individual tumor types were small."},{"rthcId":"RPEP-00041","title":"Plasma oxytocin increases in the human sexual response.","authors":"Carmichael, M S; Humbert, R; Dixen, J; Palmisano, G; Greenleaf, W; Davidson, J M","year":1987,"journal":"The Journal of clinical endocrinology and metabolism, 64(1), 27-31","doi":null,"pmid":"3782434","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00042","title":"Serum concentration of N-terminal procollagen peptide of collagen type III in schistosomal liver fibrosis.","authors":"el-Mohandes, M; Hassanein, H; el-Badrawy, N; Voss, B; Gerlach, U","year":1987,"journal":"Experimental and molecular pathology, 46(3), 383-90","doi":null,"pmid":"3109933","tags":["collagen","biomarker","liver-fibrosis"],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"Serum levels of the N-terminal procollagen type III peptide (PIIINP) showed a high correlation with the degree of liver fibrosis in patients with schistosomiasis. This peptide biomarker tracked with histopathological findings from liver biopsies, suggesting it could serve as a non-invasive marker to monitor the dynamic process of liver scarring — something a one-time biopsy cannot capture.","whyItMatters":"Liver biopsy is painful, invasive, and only provides a snapshot of damage at one moment. A blood-based peptide biomarker that reflects ongoing fibrosis activity could allow doctors to track disease progression over time without repeated biopsies. This early study helped establish PIIINP as a clinically useful marker, a concept that has since expanded to many liver diseases beyond schistosomiasis.","specificNumbers":"High correlation between serum PIIINP and histological fibrosis grade · Liver function tests correlated with histopathological diagnosis","methodology":"Researchers measured serum concentrations of procollagen type III peptide and standard liver function tests in patients with schistosomiasis mansoni. These results were compared against histopathological diagnosis from liver biopsies to determine how well the blood marker correlated with the actual degree of liver fibrosis.","limitations":"The abstract provides limited quantitative data — no specific correlation coefficients, sample sizes, or sensitivity/specificity values are reported. The study focused exclusively on schistosomal liver fibrosis, so generalizability to other causes of liver fibrosis is not established. Being from 1987, the assay technology for measuring PIIINP has since improved significantly."},{"rthcId":"RPEP-00043","title":"Recent advances in the understanding of the biochemistry and clinical pharmacology of interleukin-2.","authors":"Fletcher, M; Goldstein, A L","year":1987,"journal":"Lymphokine research, 6(1), 45-57","doi":null,"pmid":"3546963","tags":["thymosin-alpha-1","immune-function","receptor-signaling","cancer"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"IL-2 is a 133-amino acid protein (molecular weight 15,420 daltons) produced by activated T-cells. Its gene sits on chromosome 4. The IL-2 receptor is a 272-amino acid protein (55,000 daltons).\n\nIL-2 does not just make immune cells copy themselves. It moves cells from a resting state (G1) through to DNA synthesis (S phase). During this process, the proto-oncogene c-myb increases 6 to 7 times above normal levels.\n\nThe most exciting clinical development: IL-2 could expand LAK cells (lymphokine-activated killer cells) and TIL (tumor-infiltrating lymphocytes) that attack cancer. Early human trials showed both therapeutic promise and significant toxicity.\n\nThymosin fraction 5 and thymosin alpha 1 could modulate IL-2 receptor expression on human blood cells, potentially increasing the effectiveness of IL-2 therapy.","whyItMatters":"This review captured a pivotal moment in cancer immunotherapy. IL-2 was about to become the first immunotherapy approved for cancer (FDA approved in 1992 for kidney cancer). The connection to thymosin alpha 1 as an IL-2 receptor enhancer suggested combination approaches that are still studied today.","specificNumbers":"","methodology":"Narrative review covering IL-2 research from 1984 to September 1986. Covered molecular biology, mechanism of action, cell biology, disease associations, animal models, early clinical trials, and interaction with thymosin peptides.","limitations":"As a 1987 review, much of the clinical data was preliminary. The toxicity of IL-2 therapy proved to be a major limitation in practice. The thymosin-IL-2 combination was promising but not yet clinically tested."},{"rthcId":"RPEP-00044","title":"Peptide quantitative structure-activity relationships, a multivariate approach.","authors":"Hellberg, S; Sjöström, M; Skagerberg, B; Wold, S","year":1987,"journal":"Journal of medicinal chemistry, 30(7), 1126-35","doi":null,"pmid":"3599020","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00045","title":"Kainic acid as a tool to study the regulation and function of opioid peptides in the hippocampus.","authors":"Hong, J S; Grimes, L; Kanamatsu, T; McGinty, J F","year":1987,"journal":"Toxicology, 46(2), 141-57","doi":null,"pmid":"2890224","tags":["opioid-peptides","neuropeptides","neuroprotection"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"A single injection of kainic acid (1 microgram) into rat brains caused seizures lasting 3 to 6 hours. During seizures, hippocampal met-enkephalin dropped 31% and dynorphin A dropped 63%, suggesting these opioid peptides were being released.\n\nBy 24 hours, levels returned to normal. By 48 hours, met-enkephalin surged to 270% of normal and dynorphin to 150%. The brain had ramped up production to replace what was used.\n\nThe biosynthetic machinery confirmed this: mRNA for preproenkephalin (the genetic template for making enkephalin) jumped to 400% of control at 6 hours. The actual precursor protein followed at 24 hours, reaching 300% of control.\n\nThe seizure-induced shaking behavior (wet-dog shakes) was directly linked to enkephalin. Naloxone (an opioid blocker) reduced the shaking. Anti-enkephalin antibodies also reduced it. Injecting enkephalin peptides into the hippocampus mimicked the shaking.","whyItMatters":"This study mapped the complete cycle of opioid peptide release and replenishment in the brain during seizures. It showed the brain has a powerful compensatory mechanism to restore its opioid supply. Understanding this process matters for epilepsy research and for understanding how the brain's natural painkillers respond to injury.","specificNumbers":"","methodology":"Rats received a single intracerebral injection of kainic acid (1 microgram). Opioid peptide levels were measured by immunoassay at multiple time points (6, 24, 48 hours). Immunocytochemistry visualized peptide location. mRNA levels were measured to track biosynthesis. Pharmacological experiments (naloxone, antibodies, direct peptide injection) tested the functional role of enkephalin in seizure behavior.","limitations":"Tested in rats, not people. The kainic acid seizure model is artificial and does not perfectly mimic human epilepsy. The study focused on the hippocampus; other brain regions may respond differently. Only one dose of kainic acid was tested."},{"rthcId":"RPEP-00046","title":"Mu-, delta-, kappa- and epsilon-opioid receptor modulation of the hypothalamic-pituitary-adrenocortical (HPA) axis: subchronic tolerance studies of endogenous opioid peptides.","authors":"Iyengar, S; Kim, H S; Wood, P L","year":1987,"journal":"Brain research, 435(1-2), 220-6","doi":null,"pmid":"2892574","tags":["opioid-peptides","receptor-signaling","hormone-optimization"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"All four tested opioid peptides (beta-endorphin, dynorphin, MEAP, and DADLE) increased plasma corticosterone (a stress hormone) in normal rats. The effects were dose-dependent and blocked by naloxone, confirming they work through opioid receptors.\n\nCross-tolerance experiments revealed which receptor each peptide uses. Rats made tolerant to one opioid were tested with others. Dynorphin(1-13) and MEAP (Met-Enk-Arg-Phe) acted at kappa-opioid receptors. The synthetic peptide DADLE acted at delta-opioid receptors.\n\nBeta-endorphin was the surprise. It did not fit neatly into the mu, delta, or kappa categories. Its corticosterone-releasing effect was maintained even in rats tolerant to all three receptor types. The researchers proposed it acts at an epsilon-opioid receptor, a debated fourth receptor type.","whyItMatters":"This study provided in vivo evidence that the brain has multiple independent opioid systems controlling stress hormones. Each endogenous opioid peptide has its own preferred receptor. This means the stress response is not controlled by a single switch but by multiple parallel circuits.","specificNumbers":"","methodology":"Rats were made tolerant to specific opioid drugs: morphine (mu), U50488H (kappa), DADLE/morphine (delta), or beta-endorphin. Each tolerant group was then tested with the other opioid peptides. Corticosterone levels measured the functional response. All peptides were given by intracerebroventricular injection (directly into the brain). This is an animal study, not tested in people.","limitations":"Tested in rats, not people. Intracerebral injection bypasses normal delivery routes. The epsilon receptor concept remains controversial and has not been definitively proven. Cross-tolerance is an indirect way to determine receptor specificity."},{"rthcId":"RPEP-00047","title":"Delta sleep inducing peptide inhibits somatostatin release via a dopaminergic mechanism.","authors":"Iyer, K S; McCann, S M","year":1987,"journal":"Neuroendocrinology, 46(1), 93-5","doi":null,"pmid":"2886936","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00048","title":"Immature circulating lymphocytes in severely malnourished Guatemalan children.","authors":"Keusch, G T; Cruz, J R; Torun, B; Urrutia, J J; Smith, H; Goldstein, A L","year":1987,"journal":"Journal of pediatric gastroenterology and nutrition, 6(2), 265-70","doi":null,"pmid":"3121832","tags":["thymosin-alpha-1","immune-function"],"studyType":"cross-sectional","evidenceStrength":"preliminary","keyFinding":"The percentage of E-rosettes (a marker of mature T-cells) was lower in 33 acutely malnourished children compared to mildly growth-retarded children from the same area. But there was considerable overlap between groups, meaning not every malnourished child had low T-cells.\n\nThis differed from studies in other countries where all severely malnourished children showed uniformly depressed T-cell markers. The authors suggested that specific nutrient deficiencies, not malnutrition overall, may drive immune problems.\n\nAdding thymosin fraction 5 to the children's blood cells in lab dishes increased E-rosette formation in a dose-dependent manner. This means immature T-cell precursors were present in the blood and could be pushed toward maturity with thymic peptides.","whyItMatters":"Malnutrition is a leading cause of immune deficiency worldwide. This study showed that malnourished children have immature T-cells that could potentially be matured with thymic peptides. It also challenged the assumption that malnutrition uniformly suppresses T-cells, suggesting specific nutrients matter more than caloric deficit.","specificNumbers":"","methodology":"Cross-sectional study of 33 severely malnourished and two groups of mildly growth-retarded Guatemalan children. E-rosette formation (sheep red blood cell rosetting) was used as a T-cell maturation marker. In vitro incubation with thymosin fraction 5 tested whether the immature cells could be matured. Tested in children's blood cells in a lab dish.","limitations":"Small study of 33 acutely ill children. The in vitro thymosin response does not guarantee in vivo benefit. No actual treatment was given to the children. E-rosettes are an outdated T-cell marker. The overlap between groups weakens the ability to draw firm conclusions."},{"rthcId":"RPEP-00049","title":"Diurnal variation in prolactin, adrenocorticotropin and corticosterone release induced by opiate agonists in intact and adrenalectomized rats.","authors":"Kiem, D T; Kanyicska, B; Stark, E; Fekete, M I","year":1987,"journal":"Neuroendocrinology, 46(6), 475-80","doi":null,"pmid":"2892145","tags":["opioid-peptides","hormone-optimization","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Beta-endorphin (0.5 microgram injected into the brain), dynorphin (1 microgram), and U50-488H (a kappa opioid drug, 10 mg/kg) all stimulated prolactin (PRL) release more in the afternoon (4-5 PM) than in the morning (8-9 AM).\n\nMorphine (10 mg/kg subcutaneous), met-enkephalin (200 micrograms), and D-Met-Pro-Enk (0.5 microgram) did not show this daily rhythm. Their prolactin response was the same regardless of time.\n\nFor corticosterone (a stress hormone), the pattern was different. Morphine, D-Met-Pro-Enk, met-enkephalin, and dynorphin could only increase corticosterone in the morning, when baseline levels were low. In the afternoon, when baseline corticosterone was already high, there was no room for further increase.\n\nRemoving the adrenal glands eliminated the circadian rhythm in prolactin responses, suggesting that natural cortisol cycling drives the time-of-day differences.","whyItMatters":"This study showed that the time of day you give an opioid peptide affects how the body responds. This has implications for anyone studying opioid effects on hormones. The finding that adrenal hormones control this rhythm connects the stress system to the opioid system in a time-dependent way.","specificNumbers":"","methodology":"Rats were tested at two time points (8-9 AM and 4-5 PM). Opioid peptides were given by intracerebroventricular injection (into the brain) or subcutaneous injection. Plasma prolactin, ACTH, and corticosterone were measured. Some rats had their adrenal glands removed to test the role of cortisol in the circadian rhythm. Tested in rats, not people.","limitations":"Tested in rats, not people. Brain injections bypass normal routes. The study used only two time points; a full 24-hour profile would be more informative. Adrenalectomy is a drastic intervention that changes many systems beyond just removing cortisol cycling."},{"rthcId":"RPEP-00050","title":"Vasopressin, oxytocin, dynorphin, enkephalin and corticotrophin-releasing factor mRNA stimulation in the rat.","authors":"Lightman, S L; Young, W S","year":1987,"journal":"The Journal of physiology, 394, 23-39","doi":null,"pmid":"2895179","tags":["oxytocin","neuropeptides","opioid-peptides"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Rats drinking 2% salt solution showed progressive increases in three neuropeptide mRNAs in the hypothalamus (a brain region controlling hormones):\n\nVasopressin, oxytocin, and dynorphin mRNAs all increased in the magnocellular neurons of the supraoptic and paraventricular nuclei. These are the brain cells that make these peptide hormones.\n\nEnkephalin mRNA was not detectable in these brain areas under normal conditions. It only appeared after 12 days of salt loading or after the acute stress of a salt injection into the abdomen.\n\nLactating mother rats (10 days postpartum) showed a very large increase in oxytocin mRNA, with smaller increases in vasopressin and dynorphin. No enkephalin or CRF (corticotrophin-releasing factor) changes were seen in lactating rats.","whyItMatters":"This study showed that the brain can dramatically ramp up production of specific neuropeptides in response to physiological demands. Salt stress and lactation each triggered distinct patterns of gene activation, revealing how the brain adapts its peptide hormone output to changing needs.","specificNumbers":"","methodology":"Rats were given 2% NaCl solution as their only drinking water for up to 12 days. A separate group received acute intraperitoneal hypertonic saline. Lactating rats (10 days) were also studied. Brain sections were processed with in situ hybridization using synthetic oligonucleotide probes for vasopressin, oxytocin, dynorphin, enkephalin, and CRF mRNAs.","limitations":"Tested in rats, not people. Salt-loading is an artificial stress model. The study measured mRNA only, which indicates gene activity but does not directly measure peptide levels. In situ hybridization was semi-quantitative, not precisely quantitative. Small group sizes were likely given the labor-intensive methods."},{"rthcId":"RPEP-00051","title":"Alterations in regional concentrations of endogenous opioids following traumatic brain injury in the cat.","authors":"McIntosh, T K; Head, V A; Faden, A I","year":1987,"journal":"Brain research, 425(2), 225-33","doi":null,"pmid":"2892572","tags":["opioid-peptides","neuroprotection"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Severe brain injury (3.0 to 4.0 atmospheres of pressure) caused dynorphin to increase significantly in five brain regions: striatum, frontal cortex, parietal cortex, pons, and medulla. These were the same regions with the worst tissue damage.\n\nBeta-endorphin decreased in the hypothalamus after severe injury but increased in the anterior pituitary after both mild and severe trauma. Enkephalin levels did not change at any injury level.\n\nThe dynorphin increase in the medulla was significantly correlated with falling mean arterial blood pressure after severe injury. This suggests dynorphin release may contribute to the cardiovascular collapse that worsens outcomes after head trauma.","whyItMatters":"This study provided the first direct measurement of opioid peptide changes after traumatic brain injury. The correlation between dynorphin and tissue damage suggested that the body's own opioid peptides might worsen brain injury, which is the rationale for testing opioid-blocking drugs like naloxone after head trauma.","specificNumbers":"","methodology":"Cats received fluid-percussion brain injury at low (1.0 to 2.0 atm) or high (3.0 to 4.0 atm) levels. Brain regions were collected at 2 hours after injury. Dynorphin, leucine-enkephalin, and beta-endorphin were measured by immunoassay. Blood pressure was monitored throughout. Tested in cats, not people.","limitations":"Tested in cats, not people. Only measured at one time point (2 hours). The correlation between dynorphin and damage does not prove dynorphin caused the damage. It could be a consequence rather than a cause. Small sample sizes typical of large animal studies."},{"rthcId":"RPEP-00052","title":"Endogenous opioids may mediate secondary damage after experimental brain injury.","authors":"McIntosh, T K; Hayes, R L; DeWitt, D S; Agura, V; Faden, A I","year":1987,"journal":"The American journal of physiology, 253(5 Pt 1), E565-74","doi":null,"pmid":"2891303","tags":["opioid-peptides","neuroprotection","cardiovascular"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Dynorphin A accumulated in injured brain regions after fluid-percussion brain injury in cats. These same regions showed significant decreases in cerebral blood flow. Enkephalin did not accumulate.\n\nThe opioid antagonist Win-(-), given 15 minutes after injury, significantly improved multiple outcomes: mean arterial blood pressure increased, EEG amplitude (brain wave activity) improved, regional cerebral blood flow recovered, and both the severity and incidence of brain hemorrhage decreased. Survival after injury was significantly better.\n\nThe control was elegant: Win-(+), the mirror-image version of the same drug that cannot bind opioid receptors, had no effect. Neither did saline. This confirmed the benefits came specifically from blocking opioid receptors.","whyItMatters":"This was strong preclinical evidence that blocking opioid receptors after brain trauma can improve outcomes. The use of an inactive mirror-image control made the results convincing. The findings supported clinical trials of opioid antagonists for traumatic brain injury.","specificNumbers":"","methodology":"Cats received fluid-percussion brain injury. Treatment groups received Win-(-) (active opioid antagonist), Win-(+) (inactive control), or saline at 15 minutes after injury. Outcomes measured: blood pressure, EEG amplitude, regional cerebral blood flow (using radioactive microspheres), hemorrhage incidence, and survival. Dynorphin and enkephalin were measured in brain regions. Tested in cats, not people.","limitations":"Tested in cats, not people. Treatment was given at 15 minutes post-injury, which is faster than typical emergency room arrival. Infarct size and 24-hour mortality were not significantly different from controls, meaning some key outcomes did not improve. Translating large-animal brain injury results to humans is uncertain."},{"rthcId":"RPEP-00053","title":"An analysis of the 'tolerance' which develops to analgetic electrical stimulation of the midbrain periaqueductal grey in freely moving rats.","authors":"Millan, M J; Członkowski, A; Herz, A","year":1987,"journal":"Brain research, 435(1-2), 97-111","doi":null,"pmid":"3427472","tags":["opioid-peptides","pain","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Electrical stimulation of the periaqueductal grey (PAG, a brain region that controls pain) initially produced strong pain relief in rats. With repeated stimulation, this relief gradually disappeared.\n\nThe tolerance was not from opioid depletion. Brain levels of beta-endorphin, met-enkephalin, and dynorphin were unchanged in tolerant rats compared to controls.\n\nIt was not a learned (conditioned) response either. Tolerant rats exposed to all the cues associated with stimulation showed no compensatory pain increase. And repeated exposure to the cues without stimulation did not restore pain relief.\n\nThe tolerance behaved exactly like drug tolerance: the dose-response curve shifted right (needed more stimulation for the same effect), it was reversed by naloxone, and it recovered spontaneously over time. Tolerant rats also showed cross-tolerance to morphine, confirming the same opioid receptor system was involved.\n\nRats showed no signs of stress during the protocol: normal body weight, food intake, temperature, adrenal weight, and hormone levels.","whyItMatters":"This study clarified why brain stimulation for chronic pain loses effectiveness over time. The tolerance is a real pharmacological phenomenon at the receptor level, not a psychological adaptation or a running out of the brain's painkiller supply. This has implications for people who use neurostimulation devices for pain management.","specificNumbers":"","methodology":"Freely moving rats received repeated electrical stimulation of the ventral PAG. Pain was measured using heat and pressure tests. Opioid peptides were measured in multiple brain regions and the pituitary. Conditioning experiments tested whether tolerance was a learned response. Stress markers were measured. Cross-tolerance to morphine was tested. All tested in rats, not people.","limitations":"Tested in rats, not people. Only one brain stimulation target was tested. The study could not directly measure receptor-level changes. The exact molecular mechanism of tolerance was not identified."},{"rthcId":"RPEP-00054","title":"Partial characterization of a novel endogenous opioid in human cerebrospinal fluid.","authors":"Miller, B E; Lipman, J J; Byrne, W L","year":1987,"journal":"Life sciences, 41(23), 2535-45","doi":null,"pmid":"3683089","tags":["opioid-peptides","pain"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Human cerebrospinal fluid (CSF) from pain-free surgery patients contained Peak B at a concentration equivalent to about 1.4 picomoles of morphine per milliliter.\n\nInjected into mouse brains, Peak B produced dose-dependent pain relief at 0.06 and 0.12 picomoles of morphine equivalents. Naloxone (an opioid blocker) reversed this effect, confirming it works through opioid receptors.\n\nIn a muscle tissue assay (mouse vas deferens), Peak B's activity was blocked by low naloxone concentrations but not high ones. This unusual pattern suggests it interacts with opioid receptors differently than known opioids.\n\nMost surprisingly, Peak B was not destroyed by trypsin or alpha-chymotrypsin, protein-digesting enzymes that break down all known opioid peptides. This means Peak B is either not a peptide or has an unusual structure that protects it from enzymes.","whyItMatters":"The human spinal fluid contains opioid substances we have not yet identified. Peak B correlates with pain status in chronic pain patients and resists enzymatic breakdown. If characterized, it could lead to new types of painkillers that last longer because they resist normal degradation.","specificNumbers":"","methodology":"Peak B was isolated from human CSF using gel filtration chromatography. Pain relief was tested in mice by intracerebroventricular injection with hot-plate and tail-flick tests. Opioid specificity confirmed with naloxone. Mouse vas deferens bioassay tested tissue-level effects. Enzyme resistance was tested with trypsin and chymotrypsin.","limitations":"Peak B was not fully characterized or identified. The active component could be a modified peptide, a non-peptide opioid, or a mixture. The mouse pain tests may not predict human effects. The number of CSF samples was small."},{"rthcId":"RPEP-00055","title":"Study of delta sleep-inducing peptide efficacy in improving sleep on short-term administration to chronic insomniacs.","authors":"Monti, J M; Debellis, J; Alterwain, P; Pellejero, T; Monti, D","year":1987,"journal":"International journal of clinical pharmacology research, 7(2), 105-10","doi":null,"pmid":"3583493","tags":["neuropeptides","sleep-peptides"],"studyType":"randomized-controlled-trial","evidenceStrength":"moderate","keyFinding":"Delta sleep-inducing peptide (DSIP) administered intravenously at 25 nmol/kg over four nights showed some improvements in sleep metrics in chronic insomniacs — including reduced awakenings, decreased waking time, and increased total sleep time — but these changes were not statistically significant compared to placebo. The only significant increases were in NREM sleep time and stage 2 sleep, but these differences already existed at baseline, undermining the finding. The authors concluded that DSIP's sleep-improving effects are of little clinical significance.","whyItMatters":"DSIP was once considered a promising natural sleep peptide, but this rigorous double-blind, placebo-controlled trial found it doesn't meaningfully improve sleep in chronic insomniacs. This is an important negative result that helps explain why DSIP never became a clinical sleep treatment despite decades of interest. It underscores the gap between a peptide's name and its actual therapeutic utility.","specificNumbers":"25 nmol/kg dose · 4 nights treatment · Double-blind crossover · NREM sleep and stage 2 increased but not beyond baseline differences","methodology":"This was a double-blind, placebo-controlled crossover trial in chronic insomnia patients. DSIP (25 nmol/kg) or placebo was administered intravenously over four nights. Sleep was measured using polysomnographic recordings, tracking sleep stages, awakenings, latency, and total sleep time.","limitations":"Sample size not specified in abstract but likely small. The short 4-night treatment period may not capture potential longer-term effects. Only one dose was tested. The IV route of administration limits practical applicability. The crossover design, while rigorous, may have been affected by carryover or period effects."},{"rthcId":"RPEP-00056","title":"An enzyme immunoassay for synthetic thymulin.","authors":"Métreau, E; Pléau, J M; Dardenne, M; Bach, J F; Pradelles, P","year":1987,"journal":"Journal of immunological methods, 102(2), 233-42","doi":null,"pmid":"3309064","tags":["thymosin-alpha-1","immune-function","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"The new enzyme immunoassay (EIA) for thymulin achieved a sensitivity of 32.5 ± 5 pg/mL (IC50) with a detection limit of 5 pg/mL. This was more sensitive than previously available radioimmunoassays.\n\nThe test was highly specific. It did not cross-react with thymosin alpha 1, thymopoietin II, or TP5 (another thymic peptide). Both the zinc-bound (biologically active) and zinc-free forms of thymulin showed the same immunoreactivity.\n\nMapping studies showed that the minimum peptide structure needed for detection was the C-terminal portion from lysine-3 to asparagine-9 (7 of the 9 amino acids).","whyItMatters":"Measuring thymulin in blood is one of the best ways to assess thymic function. This more sensitive test made it possible to track thymulin levels in diseases where thymic function declines, including aging, AIDS, and autoimmune conditions.","specificNumbers":"","methodology":"Classical competition immunoassay using thymulin conjugated to acetylcholinesterase as the tracer. Specific polyclonal rabbit anti-thymulin antibodies were used. Microtiter plates were coated with mouse monoclonal anti-rabbit IgG. Synthetic thymulin analogs were tested to map the epitope. Cross-reactivity with other thymic hormones was tested.","limitations":"This is a methods paper, not a clinical study. The assay was validated with synthetic peptides and needs further validation in clinical samples. The polyclonal antibody approach means batch-to-batch variation is possible."},{"rthcId":"RPEP-00057","title":"Localization of thymosin alpha 1 production to thymus medullary epithelial cells by use of monoclonal antibodies.","authors":"Oates, K K; Naylor, P H; Goldstein, A L","year":1987,"journal":"Hybridoma, 6(1), 47-59","doi":null,"pmid":"2445653","tags":["thymosin-alpha-1","immune-function"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Eight monoclonal antibodies against thymosin alpha 1 were produced from mice immunized with synthetic thymosin alpha 1. The antibodies were screened using both solid-phase ELISA and liquid-phase radioimmunoassay for maximum specificity.\n\nUsing indirect immunofluorescence on perfused rat thymus tissue, thymosin alpha 1-containing cells were found primarily in the thymic medulla. This confirmed earlier studies that used less specific polyclonal antibodies.\n\nThe monoclonal antibodies provide a standardized, unlimited supply of reagent compared to the variable polyclonal antisera used previously. They can be used for both in vitro and in vivo studies of thymosin alpha 1 location and function.","whyItMatters":"Knowing exactly where thymosin alpha 1 is made in the thymus helps understand how the gland trains immune cells. The medullary location is significant because this is where T-cells undergo their final maturation steps before entering the bloodstream.","specificNumbers":"","methodology":"BALB/c mice were immunized with synthetic thymosin alpha 1. Spleen cells were fused with myeloma cells to create hybridomas. Antibody-producing clones were screened by ELISA and radioimmunoassay. Eight specific clones were characterized for heavy chain class and epitope specificity. Indirect immunofluorescence was performed on perfused rat thymus sections.","limitations":"Only tested in rat thymus tissue. Did not examine extra-thymic sources of thymosin alpha 1. The monoclonal antibodies were characterized for specificity but their utility in all tissue types was not proven. No functional studies were performed."},{"rthcId":"RPEP-00058","title":"Effects of delta-sleep-inducing peptide on 24-hour sleep-wake behaviour in severe chronic insomnia.","authors":"Schneider-Helmert, D","year":1987,"journal":"European neurology, 27(2), 120-9","doi":null,"pmid":"3622582","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00059","title":"Peptide opioid antagonist separates peripheral and central opioid antitransit effects.","authors":"Shook, J E; Pelton, J T; Hruby, V J; Burks, T F","year":1987,"journal":"The Journal of pharmacology and experimental therapeutics, 243(2), 492-500","doi":null,"pmid":"2824748","tags":["opioid-peptides","gut-healing","pain"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Peripheral mu-opioid receptors in the gut can independently slow gastrointestinal transit. The peptide agonist PL017 slowed gut transit at 0.37 mg/kg but did not produce pain relief until 30 mg/kg, about 80 times higher. This proves gut mu receptors work independently of brain receptors.\n\nDelta and kappa opioid receptors in the gut also slowed transit, but less powerfully than mu receptors.\n\nThe key finding: a peptide opioid antagonist that cannot cross the blood-brain barrier blocked morphine's gut-slowing effect without reducing its painkilling activity. This pharmacological separation means constipation and pain relief work through different receptor populations (gut vs brain).","whyItMatters":"Constipation is the most common side effect of opioid painkillers. This study proved constipation is caused by gut receptors, not brain receptors. This finding led directly to the development of peripheral opioid antagonists like methylnaltrexone (Relistor), which is now FDA-approved to treat opioid-induced constipation without reducing pain relief.","specificNumbers":"","methodology":"Mice received subcutaneous opioid agonists selective for mu, delta, and kappa receptors. Gastrointestinal transit was measured by tracking a charcoal meal through the gut. Pain was measured using the hot-plate test. Brain-impermeant peptide antagonists were given to separate central from peripheral effects. Multiple receptor types and routes of administration were tested.","limitations":"Tested in mice, not people. The blood-brain barrier permeability of peptide antagonists may differ between mice and humans. Only acute dosing was studied. Chronic opioid use may change the peripheral/central balance."},{"rthcId":"RPEP-00060","title":"Corticosterone-releasing activity of immune mediators.","authors":"Torres-Alemán, I; Rejas, M T; Barasoaín, I; Borrell, J; Guaza, C","year":1987,"journal":"Life sciences, 40(10), 929-34","doi":null,"pmid":"3029527","tags":["thymosin-alpha-1","immune-function","hormone-optimization"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Thymosin alpha-1 and lymphokine-containing supernatants directly stimulated both basal and corticotropin-induced corticosterone secretion from adrenal cells.","whyItMatters":"This study provided early evidence of a direct molecular link between the immune system and hormonal stress response, suggesting immune peptides can influence stress physiology.","specificNumbers":"","methodology":"Researchers used an in vitro perifusion system with rat adrenal cells, exposing them to lymphokine-containing supernatants from mitogen-stimulated rat spleen cells and thymosin alpha-1, then measuring corticosterone output.","limitations":"This was an in vitro study using isolated rat adrenal cells, which may not fully represent how these interactions work in a living organism. No human data was included."},{"rthcId":"RPEP-00061","title":"Combined high-performance liquid chromatographic-radioimmunoassay method for the analysis of endorphins, enkephalins and other neurotransmitter peptides.","authors":"Venn, R F","year":1987,"journal":"Journal of chromatography, 423, 93-104","doi":null,"pmid":"2895117","tags":["opioid-peptides","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"The new method combined HPLC (high-performance liquid chromatography) with radioimmunoassay (RIA) to measure opioid peptides in human cerebrospinal fluid, plasma, and tissues.\n\nThe key advantage: HPLC first separates beta-endorphin from its precursor beta-lipotropin and from other opioid peptides. Then RIA measures each fraction individually. This eliminates cross-reactivity, where antibodies confuse one peptide for another.\n\nThe method uses volatile solvents that evaporate cleanly without interfering with the antibody tests. This was the first combined method that could accurately measure endorphin, enkephalin, and dynorphin families in the same sample.\n\nPreliminary results from chronic pain patients' CSF were presented, demonstrating the method's practical utility.","whyItMatters":"Accurate measurement of opioid peptides in body fluids had been nearly impossible because antibody tests could not distinguish between similar peptides. This method solved that problem and enabled reliable research on opioid peptides in pain, addiction, and neurological disease.","specificNumbers":"","methodology":"HPLC separation using volatile solvents, followed by fraction collection and radioimmunoassay for specific opioid peptides. Tested on human cerebrospinal fluid, plasma, and tissue samples. Method validation included recovery, specificity, and reproducibility tests.","limitations":"Methods paper with limited clinical data. Only a small group of chronic pain patients was tested. The method is labor-intensive compared to direct RIA. Sensitivity limits were not fully detailed."},{"rthcId":"RPEP-00062","title":"Regulation of rat adrenal medullary enkephalins by glucocorticoids.","authors":"Yoburn, B C; Franklin, S O; Calvano, S E; Inturrisi, C E","year":1987,"journal":"Life sciences, 40(26), 2495-503","doi":null,"pmid":"3037215","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00063","title":"Magainins, a class of antimicrobial peptides from Xenopus skin: isolation, characterization of two active forms, and partial cDNA sequence of a precursor.","authors":"Zasloff, M","year":1987,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 84(15), 5449-53","doi":null,"pmid":"3299384","tags":["antimicrobial-peptides"],"studyType":"laboratory-study","evidenceStrength":"foundational","keyFinding":"Two closely related 23-amino-acid peptides called magainins were isolated from the skin of the African clawed frog (Xenopus laevis). These peptides kill numerous species of bacteria and fungi at low concentrations, lyse protozoa through osmotic disruption, and are water-soluble and nonhemolytic — meaning they destroy microbes without damaging red blood cells.\n\nBoth peptides derive from a common precursor protein, as confirmed by partial cDNA sequencing. They differ by only two amino acid substitutions and are potentially amphiphilic (having both water-loving and fat-loving regions), which likely explains how they interact with microbial membranes.","whyItMatters":"This 1987 paper is a landmark in antimicrobial peptide research. It was the first to characterize magainins — a discovery that launched an entire field of study into natural antimicrobial peptides as potential alternatives to conventional antibiotics. The finding that a vertebrate animal produces broad-spectrum antimicrobial peptides in its skin opened the door to understanding innate immune defense across species and inspired decades of drug development efforts.","specificNumbers":"Two peptides, each 23 amino acids; differ by 2 substitutions; broad-spectrum activity against bacteria, fungi, and protozoa; nonhemolytic at antimicrobial concentrations; derived from common precursor protein","methodology":"The researchers isolated peptides from the skin of Xenopus laevis frogs using high-pressure liquid chromatography. They characterized two active peptide forms, determined their amino acid sequences, tested antimicrobial activity against multiple bacterial, fungal, and protozoal species, checked for hemolytic toxicity, and obtained partial cDNA sequence of the precursor protein.","limitations":"This is an in vitro characterization study from 1987. Antimicrobial activity was demonstrated in laboratory conditions, not in living organisms. The mechanism of action was proposed but not directly demonstrated. Clinical applicability to human infections was not tested."},{"rthcId":"RPEP-00064","title":"Levels of endogenous opioids and effects of an opiate antagonist during regional cerebral ischemia in rats.","authors":"Andrews, B T; McIntosh, T K; Gonzales, M F; Weinstein, P R; Faden, A I","year":1988,"journal":"The Journal of pharmacology and experimental therapeutics, 247(3), 1248-54","doi":null,"pmid":"3204516","tags":["opioid-peptides","neuroprotection","cardiovascular"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"After middle cerebral artery occlusion (a stroke model) in rats, the opioid antagonist WIN at doses of 0.4 to 400 micrograms/kg produced several benefits.\n\nAll WIN doses significantly increased mean arterial blood pressure compared to saline controls. At the optimal dose of 40 micrograms/kg, rats showed significantly greater EEG (brain wave) recovery and higher neurological scores at 24 hours compared to controls.\n\nNeurological outcome correlated with brain wave recovery on the injured side, confirming the measures tracked together.\n\nHowever, 24-hour mortality and infarct (dead tissue) size were not significantly different from controls. The drug improved functional recovery without reducing the actual area of brain death.\n\nAt 1 hour after stroke, there were no significant changes in dynorphin, enkephalin, or endorphin levels in the injured vs. uninjured brain hemisphere. This was unexpected given the changes seen in trauma models.","whyItMatters":"This was one of the first dose-ranging studies of an opioid antagonist for stroke. The finding of functional improvement without infarct size reduction suggested opioid blockers may protect brain function in the penumbra (the at-risk zone around the dead tissue) rather than preventing cell death outright.","specificNumbers":"","methodology":"Rats received middle cerebral artery occlusion. WIN was given at 15 min, 3 hr, and 6 hr post-occlusion at doses from 0.4 to 400 micrograms/kg. Outcomes: blood pressure, EEG recovery, neurological scores, mortality, and infarct size at 24 hours. Opioid peptide levels measured at 1 hour. Tested in rats, not people.","limitations":"Tested in rats, not people. The stroke model (complete artery occlusion) differs from most human strokes. The lack of opioid changes at 1 hour may reflect poor timing (too early or too late). Only one time point for peptide measurement. Functional improvement without infarct reduction raises questions about durability."},{"rthcId":"RPEP-00065","title":"Opioid peptides in pituitary gland, brain regions and peripheral tissues of spontaneously hypertensive and Wistar-Kyoto normotensive rats.","authors":"Bhargava, H N; Matwyshyn, G A; Hanissian, S; Tejwani, G A","year":1988,"journal":"Brain research, 440(2), 333-40","doi":null,"pmid":"2896047","tags":["opioid-peptides","cardiovascular"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Beta-endorphin was 49% higher in the pituitary of hypertensive rats (SHR) but dramatically lower in peripheral organs: 92% lower in heart, 48% lower in adrenals, and 57% lower in kidneys compared to normal rats (WKY). In the brain, beta-endorphin was 71% lower in the striatum of SHR rats.\n\nDynorphin was 38% lower in the pituitary, 55% lower in the striatum, and 46% lower in the heart of SHR rats, but 33% higher in the hypothalamus.\n\nMet-enkephalin showed the opposite pattern in some areas: 268% higher in adrenals, 40% higher in cortex, and 33% higher in pons/medulla of SHR rats, but 40% lower in the pituitary.\n\nThe changes were not uniform. Each opioid peptide had its own distinct pattern of increases and decreases across brain regions and organs.","whyItMatters":"The widespread opioid peptide changes in genetically hypertensive rats suggest the opioid system is not just a bystander in high blood pressure. It may actively contribute to or compensate for blood pressure dysregulation. The 268% increase in adrenal enkephalin is particularly striking.","specificNumbers":"","methodology":"Eight-week-old male spontaneously hypertensive rats (SHR) and Wistar-Kyoto normotensive rats (WKY) were compared. Beta-endorphin, dynorphin, and met-enkephalin were measured by radioimmunoassay in the pituitary, five brain regions (hypothalamus, striatum, pons/medulla, midbrain, cortex), heart, kidney, and adrenal gland. Tested in rats, not people.","limitations":"Cross-sectional comparison cannot determine cause and effect. The opioid differences could cause hypertension, result from it, or be genetically linked but independent. Only one time point (8 weeks old) was studied. SHR rats have many genetic differences from WKY rats beyond blood pressure."},{"rthcId":"RPEP-00066","title":"Enterochromaffin (EC-) cells of the mammalian gastro-entero-pancreatic (GEP) endocrine system: cellular source of pro-dynorphin-derived peptides.","authors":"Cetin, Y","year":1988,"journal":"Cell and tissue research, 253(1), 173-9","doi":null,"pmid":"2901290","tags":["opioid-peptides","gut-healing","neuropeptides"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Enterochromaffin (EC) cells are the most abundant hormone-producing cells in the gut. They were known to make serotonin. Whether they also make peptides was debated for years.\n\nUsing antibodies against all three families of opioid peptide precursors, researchers tested gut tissue from dogs, guinea pigs, and humans. EC cells contained pro-dynorphin-derived peptides: dynorphin A and alpha-neo-endorphin.\n\nThey did not contain pro-opiomelanocortin derivatives (like endorphin) or pro-enkephalin derivatives. Previous reports of enkephalin in EC cells were likely due to antibody cross-reactivity.\n\nThe number and staining characteristics of opioid-positive EC cells varied considerably between species and between different segments of the gut, suggesting species-specific processing of the dynorphin precursor.","whyItMatters":"EC cells are the gut's largest endocrine cell population. Finding that they produce dynorphin alongside serotonin means these cells can simultaneously modulate gut motility, secretion, and pain through two major signaling systems. This dual role may explain some of the complex effects of gut hormones on digestion and pain.","specificNumbers":"","methodology":"Immunohistochemistry on semithin serial sections of gastrointestinal mucosa from dogs, guinea pigs, and humans. A panel of antisera against pro-opiomelanocortin, pro-enkephalin, and pro-dynorphin derivatives was used. Combined with fluorescence histochemistry and serotonin immunocytochemistry to confirm EC cell identity.","limitations":"Immunohistochemistry can detect proteins but cannot measure their amounts or confirm they are biologically active. The species variation means dog or guinea pig findings may not perfectly represent human gut. The functional significance of dynorphin in EC cells was not tested."},{"rthcId":"RPEP-00067","title":"Tissue content of opioid peptides in the myenteric plexus-longitudinal muscle of guinea-pig small intestine.","authors":"Corbett, A D; McKnight, A T; Kosterlitz, H W","year":1988,"journal":"Journal of neurochemistry, 51(1), 32-7","doi":null,"pmid":"3379412","tags":["opioid-peptides","gut-healing"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"The myenteric plexus (the nerve network that controls gut movement) of guinea pig small intestine contained a well-defined mix of opioid peptides.\n\nMet-enkephalin dominated at 405 pmol/g of tissue. Three other enkephalin-related peptides were present at 90 to 100 pmol/g each. Two rarer enkephalin forms (BAM-18 and Met-enkephalyl-Arg-Arg-Val-NH2) were present at 24 and 5 pmol/g.\n\nDynorphin-family peptides (alpha-neoendorphin, beta-neoendorphin, dynorphin A(1-8), and dynorphin B) were all present at 12 to 15 pmol/g. Full-length dynorphin A was very scarce at only 0.8 pmol/g.\n\nNo beta-endorphin was detected.\n\nThe two rare enkephalin forms (BAM-18 and MERV-NH2) had an unusual receptor profile: they preferred mu and kappa opioid receptors rather than the delta receptors that most enkephalins favor. This means they may have different functional roles in the gut.","whyItMatters":"This was the most complete map of opioid peptides in gut nerve tissue at its time. The dominance of enkephalins over dynorphins, and the absence of endorphin, shows the gut's opioid system has a very different composition than the brain. The unusual receptor profiles of rare enkephalins suggest specialized roles in gut regulation.","specificNumbers":"","methodology":"Two-step HPLC separation followed by bioassay on mouse vas deferens tissue, with naloxone confirmation of opioid specificity. Guinea pig small intestine myenteric plexus tissue was extracted and analyzed. Receptor binding profiles were determined for each peptide.","limitations":"Tested in guinea pig tissue only. Human gut opioid peptide profiles may differ. The bioassay method measures activity rather than exact mass. Only one segment of the small intestine was analyzed."},{"rthcId":"RPEP-00068","title":"Effects of morphine and opioid peptides on plasma levels of atrial natriuretic peptide.","authors":"Crum, R L; Brown, M R","year":1988,"journal":"Life sciences, 43(10), 851-8","doi":null,"pmid":"2901019","tags":["opioid-peptides","natriuretic-peptides","cardiovascular"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Morphine injected into the brain (intracerebroventricular) was 10 times more potent than intravenous morphine at increasing plasma ANP (atrial natriuretic peptide), a hormone released by the heart that lowers blood pressure and promotes sodium excretion.\n\nLeu-enkephalin decreased plasma ANP concentrations, the opposite effect of morphine.\n\nDynorphin and beta-endorphin (given either into the brain or into the vein) did not change ANP levels at all.\n\nAll four opioids increased plasma norepinephrine and epinephrine (stress hormones), but morphine caused increases 10 to 50 times greater than the others.\n\nGanglionic blockade (cutting the nerve connection from the brain to the heart) significantly reduced morphine's ability to increase ANP, confirming the effect requires an intact autonomic nervous system.","whyItMatters":"This showed that different opioids have very different effects on cardiovascular hormones. Morphine increases ANP (which lowers blood pressure), while enkephalin decreases it. This may partly explain why morphine lowers blood pressure and has specific cardiovascular effects distinct from other opioids.","specificNumbers":"","methodology":"Awake, freely moving Sprague-Dawley rats received intracerebroventricular or intravenous injections of morphine, leu-enkephalin, dynorphin, or beta-endorphin. Plasma ANP and catecholamines (norepinephrine, epinephrine) were measured by radioimmunoassay before and after injection. Ganglionic blockade with chlorisondamine tested the role of the autonomic nervous system.","limitations":"Tested in rats, not people. Brain injection bypasses normal routes. Only acute single doses were tested. The ganglionic blockade experiment is crude and affects many systems beyond the opioid-ANP pathway."},{"rthcId":"RPEP-00069","title":"Vasopressin receptor blockade in the anterior hypothalamus suppresses aggression in hamsters.","authors":"Ferris, C F; Potegal, M","year":1988,"journal":"Physiology & behavior, 44(2), 235-9","doi":null,"pmid":"2853382","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00070","title":"Hypothalamic mu-opioid receptors in cardiovascular control: a review.","authors":"Feuerstein, G; Sirén, A L","year":1988,"journal":"Peptides, 9 Suppl 1, 75-8","doi":null,"pmid":"2856811","tags":["opioid-peptides","cardiovascular","receptor-signaling"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"The three families of opioid peptides (dynorphins, endorphins, and enkephalins) all have cardiovascular effects. Dynorphins prefer kappa receptors, enkephalins prefer delta and mu receptors, and beta-endorphin prefers mu and delta receptors.\n\nThe review focused on mu-opioid receptors in the hypothalamus, a brain region that controls many body functions including blood pressure. While the opioid system's role in normal blood pressure regulation was not well understood, cardiovascular stress clearly activates the opioid system.\n\nThe review covered both normal cardiovascular regulation and pathological states like hypertension, hemorrhagic shock, and heart failure, where opioid system changes had been documented.","whyItMatters":"Understanding how the brain's opioid system controls the heart is important for two reasons: it explains cardiovascular side effects of opioid drugs, and it identifies potential targets for new blood pressure and heart failure treatments.","specificNumbers":"","methodology":"Narrative review of existing research on opioid peptides and cardiovascular function, with emphasis on mu-opioid receptors in the hypothalamus.","limitations":"Narrative review from 1988 with limited evidence base. Much of the cited research was in animal models. The clinical significance of opioid-cardiovascular interactions was speculative at the time."},{"rthcId":"RPEP-00071","title":"Roles of central and peripheral mu, delta and kappa opioid receptors in the mediation of gastric acid secretory effects in the rat.","authors":"Fox, D A; Burks, T F","year":1988,"journal":"The Journal of pharmacology and experimental therapeutics, 244(2), 456-62","doi":null,"pmid":"2831341","tags":["opioid-peptides","gut-healing","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Morphine and other mu-opioid agonists decreased gastric acid secretion. They were more potent when injected into the brain (i.c.v.) than into the blood (i.v.), indicating a central mechanism.\n\nThe quaternary opioid antagonist naltrexone methylbromide (which cannot cross the blood-brain barrier) blocked brain-injected morphine's effect and partially blocked IV morphine's effect. This confirmed morphine reduces acid through brain receptors, even when given intravenously.\n\nThe kappa-selective agonist U-50,488H had the opposite effect: it increased gastric acid when given IV but not when given into the brain. This increase was blocked by naloxone, the muscarinic blocker atropine, and the M1-selective blocker pirenzepine.\n\nThe delta-selective agonist DPDPE did not affect acid secretion by either route.","whyItMatters":"This study showed that different opioid receptors have opposite effects on stomach acid. Mu receptors reduce acid (potentially protective) while kappa receptors increase it. This is relevant to understanding stomach ulcers in opioid users and to the gastric effects of different opioid medications.","specificNumbers":"","methodology":"Pylorus-ligated rats (to collect gastric secretions). Opioid agonists selective for mu, delta, and kappa receptors were given i.c.v. or i.v. Gastric volume and acid output were measured. Antagonists (naloxone, naltrexone methylbromide, atropine, pirenzepine) tested mechanisms. All tested in rats, not people.","limitations":"Tested in rats with pylorus ligation, an artificial model. Only acute single doses were tested. Some kappa agonists did not reproduce U-50,488H's acid-increasing effect, suggesting the finding may be drug-specific rather than receptor-specific. Species differences may limit human applicability."},{"rthcId":"RPEP-00072","title":"In vitro degradation of opioid peptides by human placental aminopeptidase M.","authors":"Furuhashi, M; Mizutani, S; Kurauchi, O; Kasugai, M; Narita, O; Tomoda, Y","year":1988,"journal":"Experimental and clinical endocrinology, 92(2), 235-7","doi":null,"pmid":"2907492","tags":["opioid-peptides","peptide-design","bioavailability"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Human placental aminopeptidase M completely degraded Met-enkephalin and Leu-enkephalin into their five constituent amino acids. The degradation rate was measured by tracking tyrosine release.\n\nThe degradation speed ranked: Met-enkephalin (fastest) > Leu-enkephalin > beta-neoendorphin > dynorphin > beta-endorphin (slowest).\n\nSmaller, simpler peptides were degraded faster than larger, more complex ones. Met-enkephalin (5 amino acids) was destroyed faster than beta-endorphin (31 amino acids).","whyItMatters":"Understanding how fast the body breaks down opioid peptides explains why some last longer than others. This information matters for designing peptide drugs that resist degradation and for understanding why injected peptides have limited duration of action.","specificNumbers":"","methodology":"Purified aminopeptidase M from human placenta was incubated with each opioid peptide. Degradation was measured by HPLC detection of released amino acids, specifically tyrosine (the first amino acid in all opioid peptides).","limitations":"In vitro study with a single purified enzyme. In the body, multiple enzymes work together. Placental enzyme may behave differently from enzymes in the brain or blood. Did not test modified or synthetic opioid peptides."},{"rthcId":"RPEP-00073","title":"Comparison of the pre-junctional effect of opioids in two blood vessels of the rabbit.","authors":"Gan, E A; Duckles, S P","year":1988,"journal":"European journal of pharmacology, 158(1-2), 21-8","doi":null,"pmid":"2851457","tags":["opioid-peptides","cardiovascular","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"In rabbit ear and saphenous (leg) arteries, both delta-selective opioid agonists (leu-enkephalin and met-enkephalin) and kappa-selective agonists (dynorphin-(1-13) and ethylketocyclazocine) inhibited nerve-stimulation-evoked contractions.\n\nDelta agonists showed a vessel-specific difference: their maximum inhibitory effect was significantly less in the saphenous artery than in the ear artery. Kappa agonists worked similarly in both vessels.\n\nYohimbine (an alpha-2 adrenergic blocker) did not enhance opioid inhibitory effects at any stimulation frequency in either vessel. This disproved the hypothesis that opioid receptors work by boosting alpha-2 receptor inhibition of noradrenaline release.","whyItMatters":"This study showed opioid peptides directly relax blood vessels by blocking nerve-driven contractions. The vessel-specific differences for delta agonists suggest different parts of the circulatory system respond differently to the same opioid signals. This matters for understanding why opioids cause blood pressure changes.","specificNumbers":"","methodology":"In vitro ring segments of rabbit ear and saphenous arteries were transmurally stimulated electrically. Opioid peptides were applied and contractile responses measured. Two stimulation patterns: short (8 Hz, 1 second) and long (2 Hz, 25 seconds). Yohimbine tested alpha-2 receptor interaction.","limitations":"In vitro study with isolated rabbit blood vessels. Results may not apply to intact animals or humans. Only two vessel types were tested. The physiological concentrations of endogenous opioid peptides at blood vessel nerve terminals are unknown."},{"rthcId":"RPEP-00074","title":"Involvement of mu opioid receptors in the amygdala in the control of feeding.","authors":"Gosnell, B A","year":1988,"journal":"Neuropharmacology, 27(3), 319-26","doi":null,"pmid":"2836755","tags":["opioid-peptides","weight-loss","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"The mu-selective opioid agonist DAGO (Tyr-D-Ala-Gly-(Me)Phe-Gly-ol) increased food intake when injected into the central nucleus of the amygdala at doses of 1 and 3 nanomoles.\n\nNeither DSLET (a delta-selective agonist) nor dynorphin A (a kappa-selective agonist) affected food intake at the same location, even at the highest dose of 3 nanomoles.\n\nDynorphin A did increase food intake when injected into the medial hypothalamus at 2 nanomoles. This shows that different brain regions use different opioid receptor types to control eating.\n\nBilateral injections of DAGO were no more effective than unilateral injections. Naloxone and the long-acting antagonist beta-chlornaltrexamine both blocked DAGO's feeding effect, confirming opioid receptor involvement.","whyItMatters":"The amygdala processes emotions and reward. Finding that mu-opioid receptors there control feeding connects the emotional/reward aspects of eating with the opioid system. This is relevant to understanding binge eating, emotional eating, and food addiction.","specificNumbers":"","methodology":"Rats received unilateral or bilateral microinjections of receptor-selective opioid agonists into the central nucleus of the amygdala or medial hypothalamus. Food intake was measured. Antagonists (naloxone, beta-chlornaltrexamine) tested specificity. All tested in rats, not people.","limitations":"Tested in rats, not people. Direct brain injection is not clinically relevant. Only three receptor types tested. The relationship between opioid-driven feeding in rats and human eating behavior is uncertain. Did not test whether this pathway is involved in normal eating or only pharmacological overstimulation."},{"rthcId":"RPEP-00075","title":"Endogenous opiates do not influence glucose and lipid metabolism in rat adipocytes.","authors":"Hauner, H; Glatting, G; Ditschuneit, H H; Pfeiffer, E F","year":1988,"journal":"Experimental and clinical endocrinology, 91(3), 350-4","doi":null,"pmid":"3075186","tags":["opioid-peptides","diabetes"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Six opioid-related substances were tested on isolated rat adipocytes (fat cells):\n- Beta-endorphin, dynorphin, met-enkephalin, leu-enkephalin, and morphine (agonists)\n- Naloxone (antagonist)\n\nNone altered insulin binding to fat cells. None changed 2-deoxy-glucose uptake (a measure of sugar absorption). None affected glucose incorporation into lipids (fat production). None showed lipolytic (fat-breaking) activity.\n\nThe conclusion: endogenous opioids do not directly affect fat cell metabolism. The glucose problems seen with opioid drugs must happen through other mechanisms, likely in the brain, liver, or pancreas.","whyItMatters":"Opioid drugs can affect blood sugar levels, which matters for diabetic patients using opioid painkillers. This study eliminated one possible mechanism: direct fat cell effects. The blood sugar changes must happen through the brain, pancreas, or liver, not through fat tissue.","specificNumbers":"","methodology":"Isolated rat adipocytes (fat cells) were exposed to opioid peptides and morphine. Four metabolic functions were measured: 125I-insulin binding, 2-deoxy-glucose uptake, glucose incorporation into lipids, and lipolysis. Naloxone was included to test whether fat cells have functional opioid receptors.","limitations":"In vitro study with isolated rat fat cells. Fat cells in the body interact with many other cell types and hormones not present in a dish. Human fat cells might respond differently. Only a limited range of concentrations may have been tested."},{"rthcId":"RPEP-00076","title":"Seizure-induced alterations in the metabolism of hippocampal opioid peptides suggest opioid modulation of seizure-related behaviors.","authors":"Hong, J S; McGinty, J F; Grimes, L; Kanamatsu, T; Obie, J; Mitchell, C L","year":1988,"journal":"NIDA research monograph, 82, 48-66","doi":null,"pmid":"2899842","tags":["opioid-peptides","neuroprotection"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"After seizures (from electroshock, kainic acid, or kindling), both dynorphin and enkephalin initially decrease in the hippocampus, indicating release. But their recovery patterns differ dramatically.\n\nEnkephalin shows a rapid, sustained rebound above normal levels after all three seizure types. Dynorphin shows a large, sustained decrease after electroshock and kindling, with slow recovery.\n\nMu-opioid receptor antagonists shortened the kindling process (where repeated mild stimulation eventually produces seizures). This strongly suggests brain opioid peptides are involved in how seizure susceptibility develops.\n\nEnkephalin in the hippocampus appears to mediate wet-dog shakes (a specific seizure behavior seen in rodents), connecting it to the opioid withdrawal syndrome.","whyItMatters":"Understanding how seizures affect the brain's opioid system matters for epilepsy treatment. If opioid peptides modulate seizure threshold and seizure-related behaviors, targeting opioid receptors could be a new approach to epilepsy management.","specificNumbers":"","methodology":"Review of the authors' own experimental work using electroconvulsive shock, kainic acid injection, and amygdaloid kindling in rats. Opioid peptide levels measured by immunoassay. Functional role tested with opioid antagonists and antisera.","limitations":"Review of primarily the authors' own work. Results are from rats and may not apply to human epilepsy. The hippocampus was the main focus; other brain regions were less studied."},{"rthcId":"RPEP-00077","title":"Prolactin release induced by opiate agonists, effect of glucocorticoid pretreatment in intact and adrenalectomized rats.","authors":"Kiem, D T; Kanyicska, B; Stark, E; Fekete, M I","year":1988,"journal":"Neuroendocrinology, 48(2), 174-9","doi":null,"pmid":"2906115","tags":["opioid-peptides","hormone-optimization","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Cortisol at 25 mg/kg given 24 hours before testing decreased prolactin release triggered by all four opioid peptides (dynorphin, beta-endorphin, met-enkephalin, D-Met-Pro-enkephalinamide) injected into the brain.\n\nActinomycin D pretreatment blocked cortisol's inhibitory effect. This means cortisol works by triggering new protein synthesis, not by directly blocking opioid receptors.\n\nIn adrenalectomized (no adrenal glands) rats, cortisol's inhibitory effect was even stronger. Maximum inhibition was reached at only 5 mg/kg, lower than the 25 mg/kg used in intact rats.\n\nCortisol did not affect opioid-induced corticosterone release. This selectivity means cortisol specifically targets the prolactin pathway, not all opioid effects.","whyItMatters":"This study showed that stress hormones (cortisol) can dampen the opioid system's ability to control prolactin. This has implications for understanding why chronic stress alters hormone levels and could explain some reproductive effects of stress (prolactin affects fertility).","specificNumbers":"","methodology":"Rats received cortisol (25 mg/kg) 24 hours before opioid peptides were injected intracerebroventricularly. Prolactin and corticosterone measured by radioimmunoassay. Actinomycin D tested whether protein synthesis was required. Adrenalectomized rats tested the effect of removing endogenous cortisol.","limitations":"Tested in rats, not people. Supraphysiological cortisol doses were used. Only acute (single dose) effects were studied. The specific protein(s) synthesized in response to cortisol were not identified."},{"rthcId":"RPEP-00078","title":"Opioids and cytosolic calcium in rat anterior pituitary: dynorphin preparation showed LHRH-like action due to contamination.","authors":"Knepel, W; Schöfl, C; Wesemeyer, G; Götz, D M","year":1988,"journal":"Experientia, 44(11-12), 1003-5","doi":null,"pmid":"2904377","tags":["opioid-peptides","peptide-safety","sourcing-quality"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"A commercially purchased synthetic dynorphin A-(1-13) raised cytosolic calcium in rat pituitary cells. However, this effect was NOT caused by dynorphin itself.\n\nWhen the same preparation was purified by HPLC, the calcium-raising effect disappeared. HPLC combined with LHRH radioimmunoassay revealed contamination with a LHRH-like compound (luteinizing hormone-releasing hormone).\n\nThe LHRH antagonist blocked the calcium effect, confirming the contamination. Pure dynorphin A-(1-13), dynorphin A-(2-13), leu-enkephalin, beta-endorphin, morphine, and U50,488H all had zero effect on pituitary calcium.\n\nLHRH itself raised calcium by about 50 nM, which was blocked by the LHRH antagonist.","whyItMatters":"This is a critical warning about peptide purity. A commercially available research-grade peptide was contaminated enough to produce completely false results. Any study using unpurified commercial peptides could be reporting artifact effects. This finding has implications for both research integrity and for consumers of research peptides.","specificNumbers":"","methodology":"Rat anterior pituitary cells were loaded with fura-2 (a fluorescent calcium indicator). Calcium changes were measured in response to opioid peptides. HPLC purification separated dynorphin from contaminants. LHRH radioimmunoassay and receptor binding studies identified the contaminant.","limitations":"Only one commercial preparation was tested. The specific contaminant was not fully identified (described as LHRH-like). The study focused on calcium effects; other contamination effects were not tested."},{"rthcId":"RPEP-00079","title":"The neuroendocrine paraventricular hypothalamus: receptors, signal transduction, mRNA and neurosecretion.","authors":"Lightman, S L","year":1988,"journal":"The Journal of experimental biology, 139, 31-49","doi":null,"pmid":"2850337","tags":["opioid-peptides","oxytocin","neuropeptides","receptor-signaling"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Endogenous opioid peptides inhibit the release of both vasopressin and oxytocin from the posterior pituitary. They also affect anterior pituitary hormones through the hypothalamic portal blood system.\n\nDynorphin mRNA co-exists in the same neurons as vasopressin. Stimuli that increase vasopressin secretion (like salt loading) also increase dynorphin mRNA accumulation. This parallel regulation strongly suggests dynorphin has a genuine role alongside vasopressin.\n\nPro-enkephalin A mRNA co-exists with CRF in a different group of hypothalamic cells. Stresses that increase CRF mRNA also increase pro-enkephalin mRNA in the same area.\n\nThe co-existence of opioid peptides with established hormones in the same cells, combined with their coordinated regulation, provides powerful evidence that opioids are genuine neuroendocrine regulators, not incidental bystanders.","whyItMatters":"This review consolidated evidence that opioid peptides are integral to the brain's hormone control system. The co-expression with established hormones and coordinated regulation changed opioid peptides from interesting curiosities to recognized neuroendocrine regulators.","specificNumbers":"","methodology":"Narrative review combining immunohistochemistry, in situ hybridization, and mRNA measurement studies. Covered receptor characterization, signal transduction, and neurosecretion in the paraventricular hypothalamic nucleus.","limitations":"Review paper with no original data. The mRNA evidence supports but does not prove functional co-release. The relative contributions of dynorphin vs vasopressin in the same neurons were not quantified."},{"rthcId":"RPEP-00080","title":"Stimulation of collagen synthesis in fibroblast cultures by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+.","authors":"Maquart, F X; Pickart, L; Laurent, M; Gillery, P; Monboisse, J C; Borel, J P","year":1988,"journal":"FEBS letters, 238(2), 343-6","doi":null,"pmid":"3169264","tags":["ghk-cu","wound-healing","skin-repair","collagen-peptides"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"GHK-Cu stimulated collagen synthesis in fibroblast cell cultures. The effect began at concentrations between 10 picomolar (10^-12 M) and 100 picomolar (10^-11 M), an extraordinarily low threshold.\n\nThe stimulation maximized at 1 nanomolar (10^-9 M). Above this concentration, the effect plateaued.\n\nThe collagen increase was independent of cell number changes. GHK-Cu was not simply making more cells; it was making existing cells produce more collagen.\n\nA GHK tripeptide sequence (glycine-histidine-lysine) exists naturally within the alpha 2(I) chain of type I collagen. The authors proposed that when wounds break down collagen, proteases could release GHK fragments. These fragments would then bind copper and stimulate new collagen production at the wound site, creating a self-healing feedback loop.","whyItMatters":"This study provided the biochemical basis for GHK-Cu's wound healing effects. The picomolar activity is remarkable because most peptides need much higher concentrations to work. The collagen feedback theory (wounds release GHK, which stimulates repair) is elegant and explains why this peptide is found in blood plasma.","specificNumbers":"","methodology":"Fibroblast cell cultures were treated with GHK-Cu at various concentrations. Collagen synthesis was measured biochemically. Cell counting confirmed the effect was not due to increased cell proliferation. Structural analysis identified the GHK motif within type I collagen.","limitations":"In vitro cell culture study. The picomolar activity is impressive but needs confirmation in living tissue and whole organisms. The collagen feedback theory from wound sites, while logical, was not directly demonstrated. Only fibroblasts were tested; effects on other cell types were not examined."},{"rthcId":"RPEP-00081","title":"Inflammation of the hind limb as a model of unilateral, localized pain: influence on multiple opioid systems in the spinal cord of the rat.","authors":"Millan, M J; Członkowski, A; Morris, B; Stein, C; Arendt, R; Huber, A; Höllt, V; Herz, A","year":1988,"journal":"Pain, 35(3), 299-312","doi":"10.1016/0304-3959(88)90140-6","pmid":"2906425","tags":["opioid-peptides","pain","inflammation"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Within 24 hours of inflammation, dynorphin increased specifically in the ipsilateral (same-side) dorsal horn of the spinal cord. Met-enkephalin, leu-enkephalin, and opioid receptor densities did not change.\n\nThe inflamed paw showed pronounced supersensitivity to morphine's painkilling effect against pressure pain, starting at 24 hours and increasing at 1 week.\n\nOpioid antagonists (naloxone and the kappa-preferring MR 2266) made the pain worse, suggesting endogenous opioids were already partially controlling the pain.\n\nBy 3-5 weeks, inflammation had spread to the opposite paw. Dynorphin was now elevated bilaterally and in the cervico-thoracic cord. Met-enkephalin and leu-enkephalin also rose bilaterally. Adrenal glands were enlarged and plasma beta-endorphin was elevated, signs of chronic stress.\n\nNo changes in mu, delta, or kappa receptor density were found at any time point.","whyItMatters":"This study mapped the complete trajectory of how local inflammation reshapes the spinal cord's opioid system. The early selective dynorphin response, morphine supersensitivity, and eventual spread to the whole opioid system provide a detailed model of how chronic pain develops and why it becomes harder to treat over time.","specificNumbers":"","methodology":"Rats received Mycobacterium butyricum in one hind paw. Pain was measured with pressure and heat tests over 5 weeks. Opioid peptides measured by immunoassay in spinal cord segments. Opioid receptor binding measured by autoradiography. Morphine sensitivity and opioid antagonist effects tested.","limitations":"Tested in rats with an artificial inflammation model. The 5-week timeline may not match human chronic pain development. Opioid peptide measurements were limited to a few time points. Did not test whether the opioid changes were beneficial or detrimental."},{"rthcId":"RPEP-00082","title":"The role of corticotropin-releasing factor in the pathogenesis of major depression.","authors":"Nemeroff, C B","year":1988,"journal":"Pharmacopsychiatry, 21(2), 76-82","doi":null,"pmid":"3293091","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00083","title":"Concomitant changes in the in vitro and in vivo release of opioid peptides and luteinizing hormone-releasing hormone from the hypothalamus following blockade of receptors for corticotropin-releasing factor.","authors":"Nikolarakis, K E; Almeida, O F; Sirinathsinghji, D J; Herz, A","year":1988,"journal":"Neuroendocrinology, 47(6), 545-50","doi":null,"pmid":"2840600","tags":["opioid-peptides","neuropeptides","fertility","hormone-optimization"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Alpha-helical CRF9-41 (a CRF receptor blocker) applied to hypothalamic slices in vitro caused beta-endorphin and met-enkephalin to drop significantly within 10 minutes. At the same time, LHRH (luteinizing hormone-releasing hormone) rose significantly.\n\nDynorphin also decreased but the change was not statistically significant.\n\nWhen the antagonist was removed, the pattern reversed within 10 minutes: beta-endorphin, met-enkephalin, and dynorphin rose back up while LHRH fell back down.\n\nThe same results were obtained in vivo using push-pull perfusion of the arcuate-median eminence region in anesthetized rats. This confirmed the in vitro findings in living animals.","whyItMatters":"This study proved that the CRF-opioid-LHRH pathway operates in both isolated tissue and living animals. The reciprocal relationship (opioids down = LHRH up) and rapid timing (10 minutes) show this is a tightly regulated system. It explains how stress suppresses reproduction at the neuroendocrine level.","specificNumbers":"","methodology":"In vitro: hypothalamic slices perifused with CRF antagonist. In vivo: push-pull perfusion of the arcuate-median eminence in chloral hydrate-anesthetized rats. All four peptides measured simultaneously in each sample by radioimmunoassay.","limitations":"In vivo experiments used anesthetized rats, which may alter neuroendocrine function. Only one concentration of the CRF antagonist was tested. The study did not identify which specific CRF receptor subtype is involved."},{"rthcId":"RPEP-00084","title":"Pre- and postsynaptic actions of GABA on the release of hypothalamic gonadotropin-releasing hormone (GnRH).","authors":"Nikolarakis, K E; Loeffler, J P; Almeida, O F; Herz, A","year":1988,"journal":"Brain research bulletin, 21(4), 677-83","doi":null,"pmid":"3061570","tags":["opioid-peptides","neuropeptides","fertility"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"GABA at concentrations from 10^-8 to 10^-4 M caused a dose-dependent increase in GnRH release from rat hypothalamic slices. The GABA-A receptor agonist isoguvacine replicated this, while the GABA-B agonist baclofen had no effect. The GABA-A antagonist SR95103 blocked the GABA effect.\n\nBlockade of nerve conduction with tetrodotoxin abolished GABA's stimulatory effect, meaning it works through neural circuits, not directly on GnRH cells.\n\nNaloxone (opioid blocker) prevented GABA-induced GnRH release. The CRF antagonist also blocked it. CRF itself decreased GnRH release, and GABA could not reverse this.\n\nGABA stimulated the release of beta-endorphin, dynorphin, and met-enkephalin from the same tissue, connecting opioid peptide release to the control of reproduction.","whyItMatters":"This study mapped a complex signaling chain: GABA releases CRF and opioid peptides, which in turn control GnRH release. Understanding this pathway matters for fertility, because GnRH controls the entire reproductive hormone cascade.","specificNumbers":"","methodology":"Rat hypothalamic slices were perifused in vitro. GnRH and opioid peptides were measured in the effluent by radioimmunoassay. GABA receptor agonists, antagonists, tetrodotoxin, CRF, CRF antagonist, and naloxone were tested.","limitations":"In vitro hypothalamic slice preparation. The artificial conditions may not perfectly replicate in vivo signaling. Only male rats were used. Opioid peptide measurements did not distinguish between different cellular sources."},{"rthcId":"RPEP-00085","title":"Further studies on opioids and hibernation: delta opioid receptor ligand selectively induced hibernation in summer-active ground squirrels.","authors":"Oeltgen, P R; Nilekani, S P; Nuchols, P A; Spurrier, W A; Su, T P","year":1988,"journal":"Life sciences, 43(19), 1565-74","doi":null,"pmid":"2904105","tags":["opioid-peptides","receptor-signaling","sleep"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"DADLE (D-Ala2-D-Leu5 enkephalin), a delta-opioid receptor agonist, at 1.50 mg/kg/day induced summer hibernation comparable to that caused by natural Hibernation Induction Trigger (HIT).\n\nMorphine (1.50 mg/kg/day), morphiceptin (0.82 mg/kg/day), and dynorphin A (0.82 mg/kg/day) did not induce hibernation.\n\nStrikingly, morphine, morphiceptin, and dynorphin A actually antagonized HIT-induced hibernation. They blocked the natural hibernation signal.\n\nThis suggests delta-opioid receptors promote hibernation while mu and kappa opioid receptors promote the arousal (waking) state. Natural hibernation may involve a shift in the balance between these receptor systems.","whyItMatters":"Hibernation involves dramatic metabolic slowdown that could have medical applications. If delta-opioid receptors control this switch, they could theoretically be used to induce therapeutic hypothermia in stroke, cardiac arrest, or organ preservation. This is one of the most fascinating areas of opioid peptide research.","specificNumbers":"","methodology":"Summer-active thirteen-lined ground squirrels (Citellus tridecemlineatus) received continuous infusions of receptor-selective opioids. Hibernation Induction Trigger (HIT) from winter-hibernating animals was also tested alone and in combination with the opioids. Body temperature and behavioral state monitored.","limitations":"Tested in ground squirrels, a species with specialized hibernation biology. Results may not apply to non-hibernating mammals including humans. Only one delta agonist was tested. The mechanism by which delta receptors trigger hibernation was not identified."},{"rthcId":"RPEP-00086","title":"Effects of naloxone and opioid agonists on gastric excitatory responses to stimulation of the vagus nerve in cats.","authors":"Okamoto, T; Kurahashi, K; Fujiwara, M","year":1988,"journal":"British journal of pharmacology, 95(2), 329-34","doi":null,"pmid":"2906554","tags":["opioid-peptides","gut-healing","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Naloxone (100 to 1000 micrograms/kg) did not affect the initial stomach response to vagus nerve stimulation. But it dose-dependently enhanced the delayed response (from vagal afferent fibers). This means endogenous opioids normally restrain the delayed stomach excitation.\n\nMet-enkephalin was markedly more potent than the mu-agonist DAGO and the kappa-agonist dynorphin A(1-13) at inhibiting both types of vagal stomach responses.\n\nThe delta-selective agonist DPDPE mimicked met-enkephalin's inhibitory effects. The delta-selective antagonist ICI 174,864 blocked DPDPE's effects. This confirmed delta-opioid receptors mediate the gastric inhibition.\n\nThe conclusion: natural opioid peptides (likely enkephalins) tonically restrain vagus nerve-driven stomach excitation through delta receptors.","whyItMatters":"The vagus nerve is the main communication line between the brain and gut. Finding that enkephalins through delta receptors control vagal gastric responses reveals how the opioid system fine-tunes digestion. This matters for understanding gut motility disorders and opioid-related digestive side effects.","specificNumbers":"","methodology":"Cats had their vagus nerves stimulated electrically. Stomach contractions were measured as gastric pressure changes. Opioid agonists and antagonists were tested systemically. Delta receptor specificity confirmed with selective agonist (DPDPE) and antagonist (ICI 174,864).","limitations":"Tested in cats, not people. Only acute stimulation was studied. The relative contribution of central vs peripheral delta receptors was not separated. Anesthesia likely affected the results."},{"rthcId":"RPEP-00087","title":"Regulation of human natural cytotoxicity by enkephalins and selective opiate agonists.","authors":"Oleson, D R; Johnson, D R","year":1988,"journal":"Brain, behavior, and immunity, 2(3), 171-86","doi":null,"pmid":"2907409","tags":["opioid-peptides","immune-function"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Met-enkephalin, leu-enkephalin, dynorphin (1-13), DSLET (delta agonist), and DAGO (mu agonist) were tested on human NK cells from healthy donors after 18-hour incubation.\n\nThe results were bidirectional: populations with low baseline NK activity showed enhancement. Populations with high baseline NK activity showed suppression. This immunoregulatory pattern was consistent across different opioid peptides.\n\nThe effect was confirmed in a serum-free system with recombinant interferon-alpha, ruling out serum-factor interference.\n\nNaloxone displayed both antagonist properties (blocking opioid effects) and direct immunomodulatory effects. This suggested lymphocytes themselves may produce opioid peptides in culture, creating an autocrine signaling loop.","whyItMatters":"This was one of the first studies showing opioid peptides regulate human immune function bidirectionally. Rather than simply boosting or suppressing immunity, they normalize it. This has implications for stress, pain, and addiction research, where opioid system disruption may lead to immune dysfunction.","specificNumbers":"","methodology":"Human peripheral blood mononuclear cells from healthy donors enriched for T cells and LGL by nylon wool columns. 18-hour preincubation with opioid peptides. NK activity measured by standard 51Cr release assay against K562 target cells. Serum-free confirmation with recombinant interferon-alpha.","limitations":"In vitro study with an 18-hour incubation that may not reflect in vivo exposure. Donor variability was large. The mechanism behind the bidirectional effect was not identified. Only NK cells were tested; other immune functions may respond differently."},{"rthcId":"RPEP-00088","title":"Central nervous system neuropeptides after peripheral nerve deafferentation.","authors":"Panerai, A E; Sacerdote, P; Brini, A; Bianchi, M; Mantegazza, P","year":1988,"journal":"Peptides, 9(2), 319-24","doi":null,"pmid":"2453855","tags":["opioid-peptides","neuropeptides","pain","neuroprotection"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Regardless of which nerve was cut (right or left sciatic, both sciatic, right brachial plexus, saphenous, or sural), the same brain-wide pattern emerged.\n\nBeta-endorphin decreased significantly in all brain areas except the striatum. Met-enkephalin increased in all brain areas and in the affected spinal cord segments. Substance P, somatostatin, and dynorphin were unaffected.\n\nThe changes appeared within 24 hours of surgery and persisted for at least 4 months, indicating a long-lasting reorganization of the opioid system.\n\nThere was no lateralization: unilateral nerve cuts produced bilateral brain changes. This means local nerve damage triggers a global brain response.\n\nSerotonergic drugs normalized beta-endorphin levels, suggesting the serotonin system mediates the opioid changes after nerve injury.","whyItMatters":"Peripheral nerve injury causes chronic pain that involves brain-wide opioid system changes. This study showed the changes are immediate, persistent, and not limited to the injury site. This helps explain why nerve damage pain is so difficult to treat and why it affects general well-being.","specificNumbers":"","methodology":"Rats underwent section of various nerves: right sciatic, left sciatic, bilateral sciatic, right brachial plexus, saphenous, or sural. Neuropeptides measured by radioimmunoassay in brain areas (left and right separately) and spinal cord segments at 24 hours and 4 months. Serotonergic agents tested for reversal.","limitations":"Tested in rats, not people. Acute nerve transection is more severe than most human nerve injuries. Only two time points (24 hours and 4 months) were measured. The functional significance of these peptide changes for pain behavior was not directly tested."},{"rthcId":"RPEP-00089","title":"The difference in stress-induced analgesia in C57BL/6 and DBA/2 mice: a search for biochemical correlates.","authors":"Przewłocka, B; Vetulani, J; Lasoń, W; Dziedzicka, M; Silberring, J; Castellano, C; Przewłocki, R","year":1988,"journal":"Polish journal of pharmacology and pharmacy, 40(5), 497-506","doi":null,"pmid":"2908136","tags":["opioid-peptides","pain","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"DBA mice had higher baseline pain thresholds than C57 mice. But C57 mice showed much greater stress-induced analgesia (pain relief from stress).\n\nThe opioid systems differed genetically: DBA mice had significantly more dynorphin in the hypothalamus and neurointermediate pituitary. C57 mice had lower KD values (better affinity) for spinal mu receptors but higher KD (lower affinity) for cerebral kappa receptors.\n\nUnder stress, the two strains activated different opioid systems. C57 mice: beta-endorphin decreased in hypothalamus and increased in neurointermediate pituitary lobe. DBA mice: dynorphin decreased in hypothalamus and beta-endorphin increased in the anterior pituitary.\n\nBoth strains showed spinal cord dynorphin decreases under stress.","whyItMatters":"This study demonstrated that genetic differences in the opioid system produce dramatically different pain and stress responses. It helps explain why people respond differently to pain and stress, and why opioid medications work better in some people than others.","specificNumbers":"","methodology":"C57BL/6 and DBA/2 mice compared for baseline pain thresholds, opioid peptide concentrations (beta-endorphin and dynorphin in brain and pituitary), opioid receptor binding (mu and kappa), and stress-induced changes. Two stress procedures tested.","limitations":"Tested in two inbred mouse strains, which represent extreme genetic uniformity. Human opioid system variation is much more complex. Only two stress procedures tested. The causal relationship between opioid differences and behavioral differences was not established."},{"rthcId":"RPEP-00090","title":"Enkephalins interact with substance P-induced aversive behaviour in mice.","authors":"Sakurada, T; Takahashi, K; Sakurada, S; Kisara, K; Folkesson, R; Terenius, L","year":1988,"journal":"Brain research, 442(1), 191-4","doi":null,"pmid":"2451988","tags":["opioid-peptides","neuropeptides","pain"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Intrathecal (spinal cord) met-enkephalin at low doses markedly reduced the aversive behavior caused by intrathecal substance P. At these same low doses, met-enkephalin produced no measurable analgesia in the tail-flick pain test.\n\nMet-enkephalin needed much higher doses to produce general analgesia.\n\nBeta-endorphin and dynorphin-(1-17) were different. They blocked substance P-induced behavior and produced general analgesia at roughly the same doses. There was no separation between the two effects.\n\nThis suggests met-enkephalin has a specific, preferential interaction with substance P-mediated pain signaling in the spinal cord, separate from its general painkilling effects.","whyItMatters":"Substance P is one of the main pain neurotransmitters in the spinal cord. Finding that met-enkephalin specifically counteracts substance P at very low doses suggests a targeted interaction between the enkephalin and substance P systems. This could inform development of spinal pain treatments.","specificNumbers":"","methodology":"Mice received intrathecal injections of substance P (to cause aversive behavior) followed by intrathecal met-enkephalin, beta-endorphin, or dynorphin. Aversive behavior was scored. General pain relief was measured by tail-flick test. Multiple doses tested for each peptide.","limitations":"Tested in mice, not people. Intrathecal injection is an invasive route not commonly used clinically. Only one aversive behavior model was tested. The mechanism of enkephalin-substance P interaction was not identified."},{"rthcId":"RPEP-00091","title":"In vivo evidence for the specific binding of human beta-endorphin to the lung and liver of the rat.","authors":"Sato, H; Sugiyama, Y; Sawada, Y; Iga, T; Hanano, M","year":1988,"journal":"Biochemical pharmacology, 37(11), 2273-8","doi":null,"pmid":"2837232","tags":["opioid-peptides","receptor-signaling","respiratory"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Radioactive beta-endorphin injected intravenously accumulated specifically in the lung and liver but not other tissues. Four lines of evidence confirmed this was specific receptor binding, not passive trapping.\n\nFirst, adding excess unlabeled beta-endorphin reduced the labeled peptide in lung and liver.\n\nSecond, injecting unlabeled beta-endorphin via the femoral vein (which passes through the lungs first) rapidly increased blood levels of the pre-injected labeled peptide, displacing it from lung binding sites. Injection via the carotid artery (bypassing the lungs) did not have this effect.\n\nThird, immunoreactive labeled peptide that had lost its receptor-binding ability did not accumulate in lung or liver.\n\nFourth, dynorphin (1-13) and ethylketocyclazocine (kappa agonist) displaced beta-endorphin from these sites, but DADLE (delta agonist) and naloxone (mu antagonist) did not. This pharmacological profile indicates kappa-type binding sites.","whyItMatters":"The lung and liver as beta-endorphin binding sites was unexpected. These organs may serve as a peripheral opioid reservoir or clearance system. Lung kappa receptors could be involved in respiratory regulation and pain modulation.","specificNumbers":"","methodology":"Radiolabeled [125I-Tyr27]beta-endorphin injected intravenously into rats. Tissue-to-serum ratios measured. Displacement studies with selective opioid agonists and antagonists. HPLC-purified immunoreactive control peptide tested. Routes of injection varied to isolate lung-specific binding.","limitations":"Tested in rats, not people. Radiolabeled peptide studies have technical artifacts. The functional significance of lung and liver binding was not determined. Only one time point (15 minutes) was studied."},{"rthcId":"RPEP-00092","title":"Characterization of opioid receptors on isolated canine gallbladder smooth muscle cells.","authors":"Severi, C; Grider, J R; Makhlouf, G M","year":1988,"journal":"Life sciences, 42(23), 2373-80","doi":null,"pmid":"2897608","tags":["opioid-peptides","gut-healing","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Three opioid peptides caused dose-dependent contraction of isolated gallbladder muscle cells: met-enkephalin > dynorphin(1-13) > leu-enkephalin.\n\nThe contractions were blocked by the opioid antagonists naloxone and MR2266 but not by muscarinic, CCK/gastrin, or tachykinin antagonists. This confirmed the response was specifically through opioid receptors.\n\nDifferential sensitivity to preferential antagonists of mu (naloxone) and kappa (MR2266) receptors, combined with the different potencies of the three agonists, indicated the presence of mu, delta, and kappa opioid receptors on the gallbladder muscle cells.\n\nThese opioid peptides are known to be present in myenteric neurons of the gut, providing the natural source of opioid signals for gallbladder muscle.","whyItMatters":"Opioid receptors on gallbladder muscle explain why opioid drugs can affect biliary function. Opioid-induced biliary spasm (gallbladder contraction causing pain) is a known clinical problem. This study identifies the receptor basis for that side effect.","specificNumbers":"","methodology":"Smooth muscle cells isolated from canine gallbladder fundus. Contraction measured in response to met-enkephalin, dynorphin(1-13), and leu-enkephalin at various concentrations. Multiple antagonist classes tested to determine receptor specificity.","limitations":"Tested in dog gallbladder cells, not human. Isolated cells may behave differently from intact tissue. Only contraction was measured; other gallbladder functions (secretion, relaxation) were not tested."},{"rthcId":"RPEP-00093","title":"Distribution of opioid peptides in the preoptic region: immunohistochemical evidence for a steroid-sensitive enkephalin sexual dimorphism.","authors":"Simerly, R B; McCall, L D; Watson, S J","year":1988,"journal":"The Journal of comparative neurology, 276(3), 442-59","doi":null,"pmid":"2903870","tags":["opioid-peptides","neuropeptides","sexual-health","fertility"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Three opioid peptide families showed distinct, non-overlapping distributions in the preoptic brain region.\n\nBeta-endorphin fibers were mainly in the periventricular nucleus. Dynorphin B fibers were more uniformly distributed with few cell bodies. Enkephalin (peptide E) had hundreds of cell bodies, concentrated in specific nuclei.\n\nThe key sexual dimorphism: male rats had significantly more enkephalin cells in the anteroventral periventricular nucleus (AVPv) than females. This was despite the AVPv being physically larger in female rats.\n\nThis sex difference was at least partially dependent on perinatal gonadal steroids. Early hormone exposure during the critical developmental window permanently organized the number of enkephalin cells, a process called organizational hormone effects.\n\nNo sex difference was found in enkephalin cells in the anterodorsal preoptic nucleus, showing the dimorphism was region-specific, not a general property of enkephalin neurons.","whyItMatters":"Sex differences in brain opioid systems may explain sex differences in pain sensitivity, addiction risk, and reproductive behavior. The finding that perinatal hormones permanently organize these circuits means the differences are set early in life.","specificNumbers":"","methodology":"Immunohistochemistry on rat brain sections using antisera specific to each opioid peptide family (beta-endorphin, dynorphin B, peptide E). Male and female rats compared. Cross-reactivity between antisera carefully controlled. Cell counting in defined nuclei. Perinatal steroid manipulation to test organizational effects.","limitations":"Tested in rats, not people. Immunohistochemistry provides semiquantitative data. Only the preoptic region was examined in detail. The functional significance of having more enkephalin cells was not tested."},{"rthcId":"RPEP-00094","title":"Differential effects of opioid peptides administered intracerebrally in loci of self-stimulation reward of lateral hypothalamus and ventral tegmental area--substantia nigra.","authors":"Singh, J; Desiraju, T","year":1988,"journal":"NIDA research monograph, 87, 180-91","doi":null,"pmid":"2855095","tags":["opioid-peptides","addiction","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Leu-enkephalin and leu-enkephalinamide inhibited electrical self-stimulation in the substantia nigra/ventral tegmental area (SN-VTA) but not the medial forebrain bundle/lateral hypothalamus (MFB-LH). However, injection into MFB-LH facilitated self-stimulation of the distant SN-VTA.\n\nAla-leu-enkephalin injected into SN-VTA actually facilitated its self-stimulation (opposite to leu-enkephalin). The same peptide in MFB-LH facilitated SN-VTA stimulation like the other enkephalins.\n\nDynorphin A(1-13) injected into SN-VTA facilitated its self-stimulation. Injection into MFB-LH had no effect.\n\nMet-enkephalin had no direct or indirect effects in either region.\n\nThese differences likely reflect different receptor preferences in the SN-VTA neural organization.","whyItMatters":"The brain's reward system is central to addiction. Finding that different opioid peptides have opposite effects in different reward centers reveals the complexity of opioid-reward interactions. This matters for understanding opioid addiction and developing treatments.","specificNumbers":"","methodology":"Rats with electrodes in both SN-VTA and MFB-LH received microinjections of five opioid peptides into one site while recording self-stimulation at both sites. This cross-regional design revealed both direct and remote effects of opioid peptides on reward.","limitations":"Tested in rats, not people. Microinjection affects a small area and may not reflect normal opioid release. Only electrical self-stimulation was tested, which is an artificial reward. The receptor types mediating each effect were not definitively identified."},{"rthcId":"RPEP-00095","title":"Antinociceptive action of intracerebroventricularly administered dynorphin and other opioid peptides in the rat.","authors":"Tiseo, P J; Geller, E B; Adler, M W","year":1988,"journal":"The Journal of pharmacology and experimental therapeutics, 246(2), 449-53","doi":null,"pmid":"2900324","tags":["opioid-peptides","pain","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Dynorphin A produced dose-related, naloxone-reversible analgesia via intracerebroventricular injection, confirming its function as an endogenous opioid painkiller acting through kappa receptors.","whyItMatters":"This study provided key evidence that dynorphin and related opioid peptides are natural painkillers in the brain, advancing understanding of how the body's endogenous opioid system manages pain.","specificNumbers":"","methodology":"Male Sprague-Dawley rats were surgically implanted with brain ventricle cannulas. After recovery, they received injections of dynorphin A or other opioid peptides, and pain response was measured using a cold-water tail-flick assay at -10°C.","limitations":"This was an animal study with direct brain injection, a route not applicable to humans. The cold-water tail-flick test measures a specific type of acute pain that may not represent chronic pain conditions."},{"rthcId":"RPEP-00096","title":"Characterization of opioid peptide-like anticonvulsant activity in rat cerebrospinal fluid.","authors":"Tortella, F C; Long, J B","year":1988,"journal":"Brain research, 456(1), 139-46","doi":null,"pmid":"2457410","tags":["opioid-peptides","neuroprotection"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"CSF from rats that had just experienced an electroshock seizure significantly raised seizure thresholds in recipient rats when injected into their brain ventricles.\n\nThis anticonvulsant activity was blocked by high-dose naloxone and by the selective delta-opioid antagonist ICI 174,864. This identified delta-opioid receptors as the mediators.\n\nThe active substance was destroyed by heat (90°C) and by trypsin (a protein-digesting enzyme), confirming it is a peptide. It passed through 10,000 dalton membranes but not 5,000 dalton membranes, putting its size between 5,000-10,000 daltons.\n\nPost-seizure CSF had increased beta-endorphin (31 amino acids, ~3,500 daltons) but not dynorphin A, leu-enkephalin, or met-enkephalin. However, hidden met-enkephalin sequences (released by trypsin digestion of larger peptides) were found.\n\nThe size (5,000-10,000 Da) and delta-receptor specificity do not match any known opioid peptide, suggesting an undiscovered anticonvulsant opioid peptide.","whyItMatters":"The brain makes a protective opioid substance after seizures that prevents further seizures. This endogenous anticonvulsant has not been identified. If found and synthesized, it could become a new type of anti-seizure drug working through delta-opioid receptors, which are not targeted by current epilepsy medications.","specificNumbers":"","methodology":"Donor rats received maximal electroshock seizure. CSF collected and injected into recipient rats' brain ventricles. Seizure threshold measured with flurothyl. Opioid antagonists tested mechanism. Heat, trypsin, peptidase inhibitors, and ultrafiltration characterized the active substance. Opioid peptide levels measured by immunoassay.","limitations":"The active substance was not fully identified. CSF transfer experiments are artificial. The amount of protection was moderate. Only one seizure model was tested. The relationship between the beta-endorphin increase and the anticonvulsant activity was unclear."},{"rthcId":"RPEP-00097","title":"Cold swim stress-induced changes in the levels of opioid peptides in the rat CNS and peripheral tissues.","authors":"Vaswani, K K; Richard, C W; Tejwani, G A","year":1988,"journal":"Pharmacology, biochemistry, and behavior, 29(1), 163-8","doi":null,"pmid":"3353422","tags":["opioid-peptides","stress-response","endorphins","neuroscience"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Cold swim stress caused opposite changes in opioid peptide levels depending on the body region. Beta-endorphin dropped in the pituitary but surged in blood plasma by over 3-fold.","whyItMatters":"This study showed that stress does not simply raise or lower natural painkillers. Different opioid peptides change in opposite directions across body regions during the same stress event.","specificNumbers":"","methodology":"Rats underwent 5-minute cold water swims at 1°C. Researchers measured opioid peptide levels in the brain, pituitary, adrenals, and blood using radioimmunoassay. Pain response was tested with the tail-flick test.","limitations":"This was an animal study using rats, so results may not directly apply to humans. The stress model was extreme (near-freezing water), which may not reflect everyday stress responses."},{"rthcId":"RPEP-00098","title":"Immunohistochemistry of biogenic polypeptides in nerve cells and fibres of the guinea pig inferior mesenteric ganglion after perturbations.","authors":"Webber, R H; Heym, C","year":1988,"journal":"Histochemistry, 88(3-6), 287-97","doi":null,"pmid":"3366635","tags":["neuropeptides","neuroscience","peptide-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Local neurons within the ganglion contribute more peptide-containing nerve fibers than researchers previously believed. Different peptide types follow distinct pathways.","whyItMatters":"Mapping where peptide-containing nerves originate helps scientists understand how the gut nervous system communicates. This is foundational for understanding gut-brain signaling.","specificNumbers":"","methodology":"Guinea pig inferior mesenteric ganglia were studied after cutting central or peripheral nerve branches, or after transplanting the ganglion into the spleen. Immunohistochemistry was used to detect multiple peptides.","limitations":"This was an animal study in guinea pigs. The technique of cutting nerves creates an artificial situation that may not perfectly reflect normal function."},{"rthcId":"RPEP-00099","title":"Co-localization of proenkephalin- and prodynorphin-derived opioid peptides in laminae IV/V spinal neurons revealed in arthritic rats.","authors":"Weihe, E; Millan, M J; Leibold, A; Nohr, D; Herz, A","year":1988,"journal":"Neuroscience letters, 85(2), 187-92","doi":null,"pmid":"2897645","tags":["opioid-peptides","pain-management","neuroscience"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Chronic arthritis triggered spinal cord neurons to produce peptides from two different opioid precursor families in the same cells. All proenkephalin-positive cells also contained prodynorphin peptides.","whyItMatters":"Finding that pain triggers dual opioid production in single neurons reveals a previously unknown pain response. This could explain how the body tries to control chronic pain from within.","specificNumbers":"","methodology":"Serial thin sections (4-6 micron) of spinal cord from arthritic and control rats were stained with highly selective antibodies against four different opioid peptides.","limitations":"This was an animal study using a severe arthritis model. The researchers did not use colchicine treatment, which could affect detection sensitivity. Results may not directly translate to human chronic pain."},{"rthcId":"RPEP-00100","title":"Amniotic fluid thymosin alpha 1 levels increase during gestation.","authors":"Welch, R A; Lee, H H; Sokol, R J; Mutchnick, M G","year":1988,"journal":"American journal of reproductive immunology and microbiology : AJRIM, 17(3), 96-7","doi":null,"pmid":"3202234","tags":["thymosin-alpha-1","immune-function","peptide-safety"],"studyType":"cross-sectional","evidenceStrength":"preliminary","keyFinding":"Amniotic fluid thymosin alpha 1 levels were remarkably higher than newborn serum levels and increased in a logarithmic pattern with fetal age (r = 0.838).","whyItMatters":"Thymosin alpha 1 is known to help the immune system. Finding it at high levels in amniotic fluid suggests it may help prepare the fetal immune system before birth.","specificNumbers":"","methodology":"Researchers used a micro-ELISA test to measure thymosin alpha 1 in amniotic fluid samples collected at different gestational ages.","limitations":"This was a cross-sectional study measuring levels at different time points, not tracking the same pregnancies over time. The source of thymosin alpha 1 in amniotic fluid was not identified."},{"rthcId":"RPEP-00101","title":"A novel potent vasoconstrictor peptide produced by vascular endothelial cells.","authors":"Yanagisawa, M; Kurihara, H; Kimura, S; Tomobe, Y; Kobayashi, M; Mitsui, Y; Yazaki, Y; Goto, K; Masaki, T","year":1988,"journal":"Nature, 332(6163), 411-5","doi":null,"pmid":"2451132","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00102","title":"Effects of beta-endorphin, met-enkephalin, and dynorphin A on basal and stimulated insulin secretion in the mouse.","authors":"Ahrén, B","year":1989,"journal":"International journal of pancreatology : official journal of the International Association of Pancreatology, 5(2), 165-78","doi":null,"pmid":"2574736","tags":["opioid-peptides","endorphins","diabetes","metabolic-peptides"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Beta-endorphin had a dose-dependent biphasic effect on insulin secretion. Low doses inhibited and high doses stimulated insulin release. Met-enkephalin only inhibited. Dynorphin A had no effect.","whyItMatters":"This shows that the body's natural opioid peptides can fine-tune insulin release. Different opioid types have completely different effects, suggesting precise regulation of blood sugar by the opioid system.","specificNumbers":"","methodology":"Mice received intravenous injections of opioid peptides at doses from 0.06 to 64 nmol/kg, alone or combined with insulin-releasing agents (glucose, carbachol, terbutaline). Plasma insulin was measured.","limitations":"This was an animal study in mice. Intravenous injection does not mimic natural peptide release within the pancreas. Dose-response patterns may differ in humans."},{"rthcId":"RPEP-00103","title":"Regional distribution of opioidergic nerves in human and canine prostates.","authors":"Aumüller, G; Jungblut, T; Malek, B; Konrad, S; Weihe, E","year":1989,"journal":"The Prostate, 14(3), 279-88","doi":null,"pmid":"2734247","tags":["opioid-peptides","neuropeptides","neuroscience"],"studyType":"cross-sectional","evidenceStrength":"preliminary","keyFinding":"Prostatic opioid innervation comes exclusively from proenkephalin-derived peptides. No prodynorphin or pro-opiomelanocortin products were detected in either species.","whyItMatters":"This shows the prostate has a selective opioid nerve supply that may help regulate smooth muscle tone and blood flow. Understanding this could be relevant to prostate conditions.","specificNumbers":"","methodology":"Immunohistochemistry using polyclonal antisera against multiple opioid peptides was applied to prostate tissue from juvenile humans, adult humans, and adult dogs.","limitations":"This was an observational tissue study. It shows which peptides are present but not what they do. Sample sizes were small, typical for detailed histological studies."},{"rthcId":"RPEP-00104","title":"Ethanol ingestive behavior as a function of central neurotransmission.","authors":"Blum, K; Briggs, A H; Trachtenberg, M C","year":1989,"journal":"Experientia, 45(5), 444-52","doi":null,"pmid":"2566510","tags":["opioid-peptides","endorphins","neuroscience"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"The opioidergic system (beta-endorphin, enkephalin, dynorphin) is involved in both the pharmacological actions of alcohol and the craving/genetic predisposition toward alcohol abuse.","whyItMatters":"Understanding how the body's natural opioid peptides drive alcohol craving could lead to peptide-based interventions for alcohol use disorders.","specificNumbers":"","methodology":"Literature review synthesizing evidence on neurotransmitter systems — particularly opioid peptides, pineal gland function, and ventral tegmental area activity — and their relationship to ethanol intake in animal models.","limitations":"As a review article, this synthesizes existing evidence without presenting new experimental data. Most evidence discussed comes from animal models rather than human clinical studies."},{"rthcId":"RPEP-00105","title":"Antibacterial and antimalarial properties of peptides that are cecropin-melittin hybrids.","authors":"Boman, H G; Wade, D; Boman, I A; Wåhlin, B; Merrifield, R B","year":1989,"journal":"FEBS letters, 259(1), 103-6","doi":null,"pmid":"2689223","tags":["antimicrobial-peptides","peptide-drug-development","infectious-disease"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"The cecropin A(1-13)-melittin(1-13) hybrid was 100-fold more active against S. aureus and 10-fold more antimalarial than parent peptides, with no toxicity to red blood cells.","whyItMatters":"This showed that combining pieces of natural peptides can create far more powerful antimicrobials without the toxicity problems. This approach opened a new path for antibiotic development.","specificNumbers":"","methodology":"Five hybrid peptides were made using solid-phase synthesis. They were tested against gram-negative and gram-positive bacteria, malaria parasites, and sheep red blood cells in laboratory assays.","limitations":"This was a lab study only. The peptides were not tested in living animals. Stability, delivery, and cost of peptide drugs remain challenges for clinical use."},{"rthcId":"RPEP-00106","title":"The involvement of opioid peptides in stress-induced analgesia in the slug Arion ater.","authors":"Dalton, L M; Widdowson, P S","year":1989,"journal":"Peptides, 10(1), 9-13","doi":null,"pmid":"2568626","tags":["opioid-peptides","endorphins","pain-management"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Stress-induced analgesia in slugs appears mediated by endogenous opioid peptides, particularly enkephalins and beta-endorphin. The opioid pain system is evolutionarily ancient.","whyItMatters":"Finding opioid-based pain relief in slugs shows this system existed hundreds of millions of years before mammals. It is one of the most ancient and conserved peptide systems in biology.","specificNumbers":"","methodology":"Slugs were stressed by tail pinch and tested on a hot plate. Various opioid peptides were injected into the foot. Opioid antagonists and enzyme inhibitors were used to confirm the mechanism.","limitations":"Slugs have a very simple nervous system compared to mammals. The term 'analgesia' is used loosely since slugs may not experience pain the way mammals do."},{"rthcId":"RPEP-00107","title":"The posttranslational processing of prodynorphin in the rat anterior pituitary.","authors":"Day, R; Akil, H","year":1989,"journal":"Endocrinology, 124(5), 2392-405","doi":null,"pmid":"2651096","tags":["opioid-peptides","neuropeptides","neuroscience"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"The rat anterior pituitary contains at least six distinct high-molecular-weight intermediates of prodynorphin, and similar forms exist in spinal cord and hypothalamus.","whyItMatters":"Understanding how cells process prodynorphin reveals why different tissues make different final products. This affects how opioid signaling works in different parts of the body.","specificNumbers":"","methodology":"Combined radioimmunoassay with antibodies to five prodynorphin domains, gel filtration chromatography, reverse phase HPLC, immunoaffinity, and immunoprecipitation to characterize processing products.","limitations":"This was an animal study using rats. The processing pathway proposed is based on relative content of intermediates, which is indirect evidence. Human pituitary processing may differ."},{"rthcId":"RPEP-00108","title":"Expression and posttranslational processing of preprodynorphin complementary DNA in the mouse anterior pituitary cell line AtT-20.","authors":"Devi, L; Gupta, P; Douglass, J","year":1989,"journal":"Molecular endocrinology (Baltimore, Md.), 3(11), 1852-60","doi":null,"pmid":"2575215","tags":["opioid-peptides","neuropeptides","neuroscience"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"AtT-20 pituitary cells contain all the enzymes needed to process prodynorphin correctly, including at rare monobasic cleavage sites. The processed peptides were released in response to CRF stimulation.","whyItMatters":"This proved that pituitary cells have the full toolkit to process prodynorphin, even though they do not normally make it. It provided a lab model for studying how opioid peptides are made and released.","specificNumbers":"","methodology":"Rat prodynorphin cDNA was stably transfected into mouse AtT-20 cells. Peptide products were identified using gel filtration, reverse phase HPLC, and peptide-specific radioimmunoassays. Secretion was tested with CRF stimulation.","limitations":"This was an in-vitro study using an engineered cell line. Processing in living brain tissue may differ. The cells already had a secretory pathway, which aided success."},{"rthcId":"RPEP-00109","title":"Detection of Met-enkephalin and Leu-enkephalin in the posterior pituitary of the holostean fish, Amia calva.","authors":"Dores, R M; McDonald, L K; Crim, J W","year":1989,"journal":"Peptides, 10(5), 951-6","doi":null,"pmid":"2608557","tags":["opioid-peptides","neuropeptides","neuroscience"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Holostean fish have enkephalin peptides with a 3:1 met-to-leu ratio and a novel modified met-enkephalin form, but no detectable prodynorphin-derived peptides.","whyItMatters":"This suggests the enkephalin and dynorphin opioid systems may have evolved at different times. The enkephalin system appears more ancient, present even in primitive fish.","specificNumbers":"","methodology":"Pituitary and brain extracts were analyzed by immunohistochemistry, reverse phase HPLC with radioimmunoassay, and enzymatic digestion to detect extended forms.","limitations":"This was an animal study in a single fish species. The antisera used were designed for mammalian peptides and might not detect all fish opioid variants. Absence of detection does not prove absence."},{"rthcId":"RPEP-00110","title":"The neurobiology of pain and its modulation.","authors":"Dubner, R; Hargreaves, K M","year":1989,"journal":"The Clinical journal of pain, 5 Suppl 2, S1-4; discussion S4-6","doi":null,"pmid":"2520436","tags":["opioid-peptides","pain-management","neuroscience"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Pain modulation involves three opioid peptide families plus serotonin and norepinephrine. Different drug classes target different parts of this system.","whyItMatters":"This review connected basic opioid peptide science to practical pain treatments. It outlined how understanding these peptide systems led to better pain management approaches.","specificNumbers":"","methodology":"Narrative review of pain neurobiology and pharmacological approaches to pain management, summarizing advances in the field.","limitations":"This is a brief review from 1989. Many advances in pain science have occurred since. Some concepts have been refined or revised."},{"rthcId":"RPEP-00111","title":"Immunohistochemical evidence for different opioid systems in the rat superior cervical ganglion as revealed by imipramine treatment and receptor blockade.","authors":"Folan, J C; Heym, C","year":1989,"journal":"Journal of chemical neuroanatomy, 2(2), 107-18","doi":null,"pmid":"2574980","tags":["opioid-peptides","neuropeptides","neuroscience"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Prodynorphin and proenkephalin peptides in the superior cervical ganglion respond differently to drugs and denervation, confirming they operate as separate systems with different origins.","whyItMatters":"This showed that different opioid peptide systems in the same tissue respond independently to drugs. This matters for understanding how antidepressants and opioid medications affect the nervous system.","specificNumbers":"","methodology":"Rats received chronic imipramine, atropine, naloxone, or a kappa antagonist. Ganglia were processed for immunohistochemistry with antisera against four opioid peptides. Denervation experiments traced fiber origins.","limitations":"This was an animal study in rats using chronic drug administration. The doses and duration may not reflect human clinical use. Immunohistochemistry is semi-quantitative."},{"rthcId":"RPEP-00112","title":"The effect of ethanol on the biosynthesis and regulation of opioid peptides.","authors":"Gianoulakis, C","year":1989,"journal":"Experientia, 45(5), 428-35","doi":null,"pmid":"2656284","tags":["opioid-peptides","endorphins","neuroscience"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Ethanol modifies the biosynthesis, post-translational processing, and release of all three opioid peptide families differently depending on acute versus chronic exposure.","whyItMatters":"Understanding how alcohol hijacks the opioid system helps explain both why people drink and why some become addicted. This knowledge supported development of opioid-based treatments for alcoholism.","specificNumbers":"","methodology":"Literature review summarizing animal and human studies on alcohol's effects on endorphin, enkephalin, and dynorphin systems.","limitations":"This is a 1989 review drawing mainly from animal studies. Understanding of alcohol-opioid interactions has grown substantially since."},{"rthcId":"RPEP-00113","title":"Specificity of action of human brain alanyl aminopeptidase on Leu-enkephalin and dynorphin-related peptides.","authors":"Gibson, A M; McDermott, J R; Lauffart, B; Mantle, D","year":1989,"journal":"Neuropeptides, 13(4), 259-62","doi":null,"pmid":"2568598","tags":["opioid-peptides","neuropeptides","neuroscience"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Brain alanyl aminopeptidase's efficiency drops dramatically with opioid peptide chain length. Dynorphin(1-17) acts as a competitive inhibitor rather than a substrate.","whyItMatters":"This explains why different opioid peptides last different amounts of time in the brain. Longer peptides like dynorphin resist breakdown, which affects how long their signals last.","specificNumbers":"","methodology":"Enzyme was purified to homogeneity from human cerebral cortex. Kinetic analysis measured cleavage rates for a series of leu-enkephalin-related peptides of increasing length.","limitations":"This was an in-vitro study with purified enzyme. In living brain tissue, multiple enzymes act simultaneously, so the actual breakdown pattern may differ."},{"rthcId":"RPEP-00114","title":"Opioid-like activity in the cerebrospinal fluid of pain patients treated by electroacupuncture.","authors":"Ho, W K; Wen, H L","year":1989,"journal":"Neuropharmacology, 28(9), 961-6","doi":null,"pmid":"2572998","tags":["opioid-peptides","endorphins","pain-management"],"studyType":"cross-sectional","evidenceStrength":"preliminary","keyFinding":"Electroacupuncture increased measurable opioid activity in spinal fluid, including beta-endorphin (80% of patients) and dynorphin (60% of patients), plus an unidentified opioid substance.","whyItMatters":"This provided direct evidence that acupuncture triggers the release of the body's natural painkillers into the spinal fluid, supporting a biological mechanism for acupuncture's pain relief.","specificNumbers":"","methodology":"Spinal fluid collected before and after 30-minute electroacupuncture was fractionated by HPLC and assayed using mu-receptor binding and radioimmunoassay for specific peptides.","limitations":"Small study with only 13 patients. No control group (sham acupuncture). The increases were not consistent across all patients. One active fraction remained unidentified."},{"rthcId":"RPEP-00115","title":"Modulation of thymosin alpha 1 and thymosin beta 4 levels and peripheral blood mononuclear cell subsets during experimental rhinovirus colds.","authors":"Hsia, J; Sztein, M B; Naylor, P H; Simon, G L; Goldstein, A L; Hayden, F G","year":1989,"journal":"Lymphokine research, 8(4), 383-91","doi":null,"pmid":"2572736","tags":["thymosin-alpha-1","immune-function","infectious-disease"],"studyType":"RCT","evidenceStrength":"moderate","keyFinding":"Rhinovirus infection triggered significant increases in thymosin alpha 1 (p < 0.001), thymosin beta 4 (p < 0.001), and multiple immune cell types by day 5 after inoculation.","whyItMatters":"This was the first proof that a viral infection can trigger thymic hormone release. It shows thymosin alpha 1 is part of the body's early immune response to respiratory viruses.","specificNumbers":"","methodology":"Two groups of healthy volunteers were inoculated with rhinovirus. Blood was drawn at intervals. Thymosin levels were measured by RIA, and immune cell subsets were counted by flow cytometry.","limitations":"Volunteers were experimentally infected, which may not perfectly match natural colds. No placebo/uninfected control group described. The mechanism linking virus to thymosin release was not identified."},{"rthcId":"RPEP-00116","title":"Thymosin enhances the production of IL-1 alpha by human peripheral blood monocytes.","authors":"Hu, S K; Badamchian, M; Mitcho, Y L; Goldstein, A L","year":1989,"journal":"Lymphokine research, 8(3), 203-14","doi":null,"pmid":"2789315","tags":["thymosin-alpha-1","immune-function","peptide-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"TF5 stimulated IL-1 alpha (not IL-1 beta) production from monocytes. The active component was a novel basic peptide, not thymosin alpha 1.","whyItMatters":"This showed thymus peptides can directly activate immune cells called macrophages. Different thymus peptides may trigger different immune responses, suggesting a more complex regulatory system than previously thought.","specificNumbers":"","methodology":"Human peripheral blood monocytes were cultured with TF5 and its fractions. IL-1 activity was measured by bioassay and blocked with specific antibodies. Mouse peritoneal cells were examined after TF5 injection.","limitations":"This was an in-vitro study. TF5 is a crude extract containing many peptides. The novel active peptide was not fully characterized or sequenced."},{"rthcId":"RPEP-00117","title":"The human endothelin family: three structurally and pharmacologically distinct isopeptides predicted by three separate genes.","authors":"Inoue, A; Yanagisawa, M; Kimura, S; Kasuya, Y; Miyauchi, T; Goto, K; Masaki, T","year":1989,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 86(8), 2863-7","doi":null,"pmid":"2649896","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00118","title":"Age-dependency and regional distribution of enkephalinergic nerves in human prostate.","authors":"Jungblut, T; Aumüller, G; Malek, B; Melchior, H","year":1989,"journal":"Urologia internationalis, 44(6), 352-6","doi":null,"pmid":"2623785","tags":["opioid-peptides","neuropeptides","neuroscience"],"studyType":"cross-sectional","evidenceStrength":"preliminary","keyFinding":"Proenkephalin-derived peptide nerve fibers in human prostate were concentrated in the dorsolateral stroma and decreased in density with age. No prodynorphin or POMC-derived peptides were detected.","whyItMatters":"The age-related decline in enkephalin nerves could contribute to prostate changes that occur with aging. Understanding this innervation pattern may be relevant to benign prostatic conditions.","specificNumbers":"","methodology":"Immunohistochemistry with highly specific polyclonal antibodies was applied to prostate tissue from juvenile and adult humans to detect multiple opioid peptides.","limitations":"This was an observational tissue study without functional testing. The number of specimens at each age was not specified. Correlation with prostate symptoms was not assessed."},{"rthcId":"RPEP-00119","title":"Lidocaine treatment of painful diabetic neuropathy and endogenous opioid peptides in plasma.","authors":"Kastrup, J; Bach, F W; Petersen, P; Dejgård, A; Ekman, R; Jensen, S; Angelo, H","year":1989,"journal":"The Clinical journal of pain, 5(3), 239-44","doi":null,"pmid":"2577686","tags":["opioid-peptides","endorphins","pain-management","diabetes"],"studyType":"cross-sectional","evidenceStrength":"preliminary","keyFinding":"Lidocaine increased plasma beta-endorphin equally in patients and controls, but pain relief in diabetic neuropathy was not correlated with beta-endorphin changes.","whyItMatters":"This suggests lidocaine relieves diabetic nerve pain through a mechanism other than the opioid system. The beta-endorphin rise appears to be a general response to lidocaine, not specific to pain relief.","specificNumbers":"","methodology":"Blood opioid peptides were measured by radioimmunoassay before and after lidocaine infusion in 8 diabetic neuropathy patients and 10 controls. Pain was scored before and after treatment.","limitations":"Very small study with only 8 patients. Only blood peptide levels were measured, which may not reflect what happens in the nervous system. No placebo control."},{"rthcId":"RPEP-00120","title":"Central mu, delta, and kappa opioid binding sites, and brain and pituitary beta-endorphin and met-enkephalin in genetically obese (ob/ob) and lean mice.","authors":"Khawaja, X Z; Bailey, C J; Green, I C","year":1989,"journal":"Life sciences, 44(16), 1097-105","doi":null,"pmid":"2523015","tags":["opioid-peptides","endorphins","obesity","metabolic-peptides"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Genetically obese mice showed massive increases in opioid peptide levels and shifts in receptor types, with kappa receptors up 2.7-fold and mu receptors down 40%.","whyItMatters":"These striking opioid differences in obese mice suggest the opioid system plays a major role in overeating. The changes could drive excessive food intake and contribute to metabolic problems like high blood sugar and insulin resistance.","specificNumbers":"","methodology":"Brain membrane binding assays measured mu, delta, and kappa receptor levels using specific radioligands. Opioid peptide levels were quantified by radioimmunoassay in brain and pituitary tissue.","limitations":"This was an animal study using genetically obese mice (ob/ob), which lack the hormone leptin. Human obesity is much more complex and usually involves multiple genetic and environmental factors."},{"rthcId":"RPEP-00121","title":"A common cytolytic region in myotoxins, hemolysins, cardiotoxins and antibacterial peptides.","authors":"Kini, R M; Evans, H J","year":1989,"journal":"International journal of peptide and protein research, 34(4), 277-86","doi":null,"pmid":"2599766","tags":["antimicrobial-peptides","peptide-drug-development","peptide-structure"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Cytolytic peptides from diverse species converge on a common structural motif: a cationic site flanked by a hydrophobic surface. This motif is necessary and sufficient for membrane-disrupting activity.","whyItMatters":"Identifying the common structural requirement for cell-killing activity provides a blueprint for designing new antibacterial and anticancer peptides.","specificNumbers":"","methodology":"Comparative sequence analysis of cytolytic peptides from multiple species, supported by evidence from synthetic analogs and chemical modification studies.","limitations":"This is a sequence comparison study. The proposed structural motif needs experimental validation in each case. Not all peptides with this motif may be cytolytic."},{"rthcId":"RPEP-00122","title":"Computer analysis of the effect of beta-endorphin and dynorphin and related compounds on opioid binding to mouse brain membrane.","authors":"Landahl, H D; Garzon, J; Lee, N M","year":1989,"journal":"Computers in biology and medicine, 19(3), 151-62","doi":null,"pmid":"2566453","tags":["opioid-peptides","endorphins","pain-management","neuroscience"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"In a 4-site binding model, both beta-endorphin and dynorphin peptides preferred mu and delta sites, with dynorphin additionally interacting significantly with kappa sites.","whyItMatters":"Understanding which receptors each opioid peptide prefers helps explain their different biological effects and guides drug development targeting specific receptor types.","specificNumbers":"","methodology":"Competition binding assays with three tritiated opioid agonists were analyzed using a custom computer program implementing a 4-site binding model.","limitations":"In-vitro binding studies in brain membranes may not fully reflect receptor behavior in living brain tissue. The 4-site model is a simplification of complex receptor pharmacology."},{"rthcId":"RPEP-00123","title":"Beta-endorphin and dynorphin mimic the circadian immunoenhancing and anti-stress effects of melatonin.","authors":"Maestroni, G J; Conti, A","year":1989,"journal":"International journal of immunopharmacology, 11(4), 333-40","doi":null,"pmid":"2570759","tags":["opioid-peptides","endorphins","immune-function","stress-response"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Beta-endorphin and dynorphin replicated melatonin's immunoenhancing and anti-stress effects, but with complementary roles: beta-endorphin for normal conditions, dynorphin for stress states. Effects were circadian and opioid-receptor-mediated.","whyItMatters":"This showed that melatonin's immune effects work through the opioid system and follow daily rhythms. It revealed that beta-endorphin and dynorphin have complementary immune roles.","specificNumbers":"","methodology":"Mice were restraint-stressed or treated with prednisolone, then given opioid peptides at different times of day. Antibody responses, thymus weight, and antiviral resistance were measured.","limitations":"This was an animal study in mice. The doses used may not reflect natural peptide levels. The circadian effects need confirmation across different experimental conditions."},{"rthcId":"RPEP-00124","title":"Biologically active peptides in milk proteins.","authors":"Meisel, H; Frister, H; Schlimme, E","year":1989,"journal":"Zeitschrift fur Ernahrungswissenschaft, 28(4), 267-78","doi":null,"pmid":"2694639","tags":["bioactive-peptides","collagen-peptides","gut-health","immune-function"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Milk proteins contain encrypted bioactive peptide sequences that are released during digestion, including opioid-like casomorphins, mineral-binding phosphopeptides, and immunostimulating peptides.","whyItMatters":"This changed how scientists evaluate food proteins. The nutritional value of milk goes beyond basic nutrition to include biologically active peptide signals that affect multiple body systems.","specificNumbers":"","methodology":"Literature review summarizing research on bioactive peptides released from casein and whey proteins during intestinal digestion.","limitations":"This is a 1989 review. The biological significance of food-derived bioactive peptides in normal human nutrition was still being established. Doses reaching the bloodstream may be very small."},{"rthcId":"RPEP-00125","title":"Ultrastructural basis for interactions between central opioids and catecholamines. I. Rostral ventrolateral medulla.","authors":"Milner, T A; Pickel, V M; Reis, D J","year":1989,"journal":"The Journal of neuroscience : the official journal of the Society for Neuroscience, 9(6), 2114-30","doi":null,"pmid":"2566665","tags":["opioid-peptides","neuropeptides","cardiovascular","neuroscience"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"42% of enkephalin terminal targets in the blood pressure control region were catecholamine neurons. Some neurons co-contained both enkephalin and tyrosine hydroxylase.","whyItMatters":"Both opioid peptides and adrenaline-related drugs lower blood pressure when applied to this brain region. This study showed these two systems are physically connected, explaining their shared cardiovascular effects.","specificNumbers":"","methodology":"Dual immunoperoxidase and immunoautoradiographic labeling at the electron microscope level in colchicine-treated rat brain sections through the rostral ventrolateral medulla.","limitations":"This was an animal study using detailed electron microscopy in a small brain region. The functional significance of the anatomical connections was not directly tested."},{"rthcId":"RPEP-00126","title":"Effect of endogenous opioid peptides on TRH release from rat stomach in vitro.","authors":"Mitsuma, T; Hirooka, Y; Nakada, K; Nomura, A; Nogimori, T","year":1989,"journal":"Endocrinologia experimentalis, 23(1), 11-6","doi":null,"pmid":"2565806","tags":["opioid-peptides","neuropeptides","gut-health"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Three opioid peptides from different families all inhibited TRH release from rat stomach in a dose-dependent manner, reversible by naloxone.","whyItMatters":"This confirms that opioid regulation of gut TRH is not limited to one part of the digestive tract. The stomach also responds to opioid peptides by reducing hormone release.","specificNumbers":"","methodology":"Rat stomach tissue was incubated with opioid peptides and naloxone. TRH released into the medium was measured by radioimmunoassay.","limitations":"In-vitro study using isolated stomach tissue. Whether this regulation matters in living animals and what functional consequences it has remain unknown."},{"rthcId":"RPEP-00127","title":"Effects of opioid peptides on thyrotropin-releasing hormone release from the rat caecum in vitro.","authors":"Mitsuma, T; Hirooka, Y; Nakata, K; Nogimori, T","year":1989,"journal":"Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme, 21(6), 301-4","doi":null,"pmid":"2506116","tags":["opioid-peptides","neuropeptides","gut-health"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"All three families of opioid peptides inhibited TRH release from rat cecum tissue in a dose-dependent, naloxone-reversible manner.","whyItMatters":"The gut produces TRH, and opioid peptides regulate its release. This connects the opioid system to thyroid hormone regulation in the gut, suggesting a broader role for gut opioids than just pain control.","specificNumbers":"","methodology":"Rat cecum was incubated with each of six opioid peptides. TRH released into the medium was measured by radioimmunoassay. Naloxone was used to confirm opioid receptor involvement.","limitations":"This was an in-vitro study using isolated gut tissue. The physiological relevance of gut TRH regulation by opioids in living animals is unknown."},{"rthcId":"RPEP-00128","title":"Delta-sleep-inducing peptide (DSIP) stimulates the release of immunoreactive Met-enkephalin from rat lower brainstem slices in vitro.","authors":"Nakamura, A; Nakashima, M; Sakai, K; Niwa, M; Nozaki, M; Shiomi, H","year":1989,"journal":"Brain research, 481(1), 165-8","doi":null,"pmid":"2706459","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00129","title":"Prodynorphin peptide distribution in the forebrain of the Syrian hamster and rat: a comparative study with antisera against dynorphin A, dynorphin B, and the C-terminus of the prodynorphin precursor molecule.","authors":"Neal, C R; Newman, S W","year":1989,"journal":"The Journal of comparative neurology, 288(3), 353-86","doi":null,"pmid":"2571622","tags":["opioid-peptides","neuropeptides","neuroscience"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Prodynorphin peptide distribution differs substantially between hamster and rat in reproduction and emotion-related brain regions, and hamsters may process the precursor protein differently.","whyItMatters":"Species differences in dynorphin distribution in reproductive and emotional brain areas may explain behavioral differences between species, particularly in mating and stress responses.","specificNumbers":"","methodology":"Immunohistochemistry with a novel C-terminus antibody and existing dynorphin A and dynorphin B antibodies was applied to colchicine-treated and untreated hamster and rat brains.","limitations":"Comparative anatomical study between only two rodent species. The functional significance of the distribution differences was not tested. Colchicine treatment may affect results."},{"rthcId":"RPEP-00130","title":"Release of endogenous opioid peptides displaces [3H]diprenorphine binding in rat hippocampal slices.","authors":"Neumaier, J F; Chavkin, C","year":1989,"journal":"Brain research, 493(2), 292-302","doi":null,"pmid":"2765901","tags":["opioid-peptides","neuropeptides","neuroscience"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Endogenous opioid peptide release from hippocampal slices was demonstrated by competitive radioligand displacement. The strongest release occurred in stratum lacunosum moleculare of CA3.","whyItMatters":"This technique showed where opioid peptides are actually released and where they act in the hippocampus, which is crucial for understanding their role in memory and learning.","specificNumbers":"","methodology":"Rat hippocampal slices were depolarized with KCl or veratrine. Displacement of bound [3H]diprenorphine was measured by receptor autoradiography and quantitative densitometry.","limitations":"In-vitro brain slice preparation removes normal neural circuit activity. Chemical depolarization is non-physiological. The technique cannot distinguish which specific opioid peptides were released."},{"rthcId":"RPEP-00131","title":"Presynaptic auto- and allelo-receptor regulation of hypothalamic opioid peptide release.","authors":"Nikolarakis, K E; Almeida, O F; Yassouridis, A; Herz, A","year":1989,"journal":"Neuroscience, 31(1), 269-73","doi":null,"pmid":"2570378","tags":["opioid-peptides","endorphins","neuroscience","peptide-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Opioid peptides regulate each other's release through presynaptic cross-receptor mechanisms. Delta receptor blockade increased release of all three peptide types. This 'allelo-receptor' system provides complex feedback regulation.","whyItMatters":"This cross-talk means the three opioid systems are not independent. Changing one system automatically affects the others, which has important implications for opioid drug development.","specificNumbers":"","methodology":"Rat hypothalamic slices were treated with specific mu, delta, and kappa opioid antagonists. Release of beta-endorphin, dynorphin, and met-enkephalin was measured in the presence of tetrodotoxin to confirm presynaptic action.","limitations":"In-vitro hypothalamic slice study. The allelo-receptor concept needs in-vivo confirmation. The functional consequences of this cross-regulation were not tested."},{"rthcId":"RPEP-00132","title":"Molecular determinants of receptor affinity and selectivity of the natural delta-opioid agonist, dermenkephalin.","authors":"Sagan, S; Amiche, M; Delfour, A; Mor, A; Camus, A; Nicolas, P","year":1989,"journal":"The Journal of biological chemistry, 264(29), 17100-6","doi":null,"pmid":"2551895","tags":["opioid-peptides","peptide-structure","peptide-drug-development"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"The C-terminal residues Met6 and Asp7 of dermenkephalin are the primary determinants of delta-opioid receptor selectivity, overriding the mu-preferring N-terminal domain.","whyItMatters":"This work identified the molecular rules for making peptides selective for delta-opioid receptors. Delta receptors may produce pain relief with fewer side effects than mu receptors.","specificNumbers":"","methodology":"Structure-activity analysis using synthetic analogs, deletions, and hybrid peptides. Binding affinity at mu and delta sites was measured in brain membrane preparations.","limitations":"In-vitro binding study. Receptor selectivity in binding assays may not perfectly predict selectivity in functional or in-vivo settings."},{"rthcId":"RPEP-00133","title":"Steady-state levels of pro-dynorphin-related end-products from the brain of the amphibian, Xenopus laevis.","authors":"Sei, C A; Richard, R; Dores, R M","year":1989,"journal":"Brain research, 479(1), 162-6","doi":null,"pmid":"2564304","tags":["opioid-peptides","neuropeptides","neuroscience"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Alpha-neoendorphin is the major prodynorphin end product in Xenopus brain. Leu-enkephalin is produced from prodynorphin processing, not from proenkephalin, in this species.","whyItMatters":"This shows that prodynorphin processing varies across species. In frogs, the precursor is processed primarily to alpha-neoendorphin, while mammals produce more dynorphin A and B.","specificNumbers":"","methodology":"Acid extracts of frog brain were analyzed by radioimmunoassay specific for four prodynorphin peptides, combined with gel filtration chromatography and reverse phase HPLC.","limitations":"Single species study. Only one brain region (whole brain extract) was analyzed. The processing pathway is inferred from end products, not directly observed."},{"rthcId":"RPEP-00134","title":"Lack of effect of opioid peptides, morphine and naloxone on superoxide formation in human neutrophils and HL-60 leukemic cells.","authors":"Seifert, R; Burde, R; Schultz, G","year":1989,"journal":"Naunyn-Schmiedeberg's archives of pharmacology, 340(1), 101-6","doi":null,"pmid":"2552328","tags":["opioid-peptides","immune-function","endorphins"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"No opioid peptide or morphine, across a wide concentration range, affected superoxide formation in human neutrophils or HL-60 cells under defined experimental conditions.","whyItMatters":"This resolved conflicting reports by showing that previous positive findings may have been due to experimental artifacts. Opioids do not directly affect this immune cell function.","specificNumbers":"","methodology":"Human neutrophils and HL-60 cells were exposed to various opioids and immune activators. Superoxide production was measured by standard assays under carefully defined conditions.","limitations":"In-vitro study that only measured one immune function (superoxide production). Opioids may affect other aspects of immune cell behavior not tested here."},{"rthcId":"RPEP-00135","title":"A novel bovine spinal cord endoprotease with high specificity for dynorphin B.","authors":"Silberring, J; Nyberg, F","year":1989,"journal":"The Journal of biological chemistry, 264(19), 11082-6","doi":null,"pmid":"2567732","tags":["opioid-peptides","neuropeptides","neuroscience"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"A novel endoprotease with high specificity for dynorphin B (Km = 11 µM) was identified in bovine spinal cord. It does not act on other prodynorphin-derived peptides.","whyItMatters":"This enzyme provides a mechanism for selectively converting one opioid peptide into another. It could fine-tune opioid signaling by specifically controlling dynorphin B levels in the spinal cord.","specificNumbers":"","methodology":"Enzyme was purified 230-fold from bovine spinal cord extract using conventional chromatography. Characterized by SDS-PAGE, pH optimum, inhibitor profile, and substrate specificity.","limitations":"In-vitro study using purified enzyme. The enzyme's role in living tissue and its regulation have not been studied. Only bovine spinal cord was examined."},{"rthcId":"RPEP-00136","title":"Cocaine selectively increases striatonigral dynorphin levels by a dopaminergic mechanism.","authors":"Sivam, S P","year":1989,"journal":"The Journal of pharmacology and experimental therapeutics, 250(3), 818-24","doi":null,"pmid":"2476548","tags":["opioid-peptides","neuropeptides","neuroscience"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Subchronic cocaine selectively increased striatonigral dynorphin through a dopaminergic mechanism requiring both D1 and D2 receptors. Enkephalin and substance P were unaffected.","whyItMatters":"Dynorphin increases may represent the brain's attempt to counteract cocaine's rewarding effects. This compensatory response could contribute to withdrawal symptoms and tolerance.","specificNumbers":"","methodology":"Rats received cocaine (20 mg/kg/day for 4 days). Brain peptide levels were measured by radioimmunoassay. Dopamine involvement was confirmed using 6-OHDA lesions and D1/D2 antagonists.","limitations":"Animal study using a relatively short cocaine regimen. Human cocaine use patterns are more variable. The functional consequences of elevated dynorphin were not directly tested."},{"rthcId":"RPEP-00137","title":"Characterization of the immunoregulatory properties of thymosin alpha 1 on interleukin-2 production and interleukin-2 receptor expression in normal human lymphocytes.","authors":"Sztein, M B; Serrate, S A","year":1989,"journal":"International journal of immunopharmacology, 11(7), 789-800","doi":null,"pmid":"2599716","tags":["thymosin-alpha-1","immune-function","peptide-signaling"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Thymosin alpha 1 modulates an early event in T cell activation. A 30-minute preincubation is sufficient to prime both CD4+ and CD8+ T cells, but macrophage-derived IL-1 is required for the enhanced response.","whyItMatters":"This revealed that thymosin alpha 1 works fast and directly on T cells. It primes them to respond more strongly to immune challenges, which explains its clinical immunostimulating effects.","specificNumbers":"","methodology":"Human mononuclear cells, purified T cells, and CD4+/CD8+ subsets were preincubated with thymosin alpha 1 or TF5. IL-2 production and IL-2 receptor expression were measured after PHA stimulation. Two-color flow cytometry identified target cell populations.","limitations":"In-vitro study with human cells. The concentrations used may not reflect achievable levels in patients. The early event modified by thymosin was not molecularly identified."},{"rthcId":"RPEP-00138","title":"Intrathecal [Met5]enkephalin antibody blocks analgesia induced by intracerebroventricular beta-endorphin but not morphine in mice.","authors":"Tseng, L L; Suh, H H","year":1989,"journal":"European journal of pharmacology, 173(2-3), 171-6","doi":null,"pmid":"2533906","tags":["opioid-peptides","endorphins","pain-management","neuroscience"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Beta-endorphin produces spinal analgesia by selectively releasing met-enkephalin. Morphine does not use this mechanism. The effect is specific to the tail-flick (spinal) but not hot-plate (supraspinal) response.","whyItMatters":"This proved that the body's natural painkiller beta-endorphin and the drug morphine relieve pain through fundamentally different spinal cord mechanisms, even though both activate opioid receptors.","specificNumbers":"","methodology":"Mice received intrathecal injections of opioid peptide antibodies followed by intracerebroventricular beta-endorphin or morphine. Pain was assessed by tail-flick and hot-plate tests.","limitations":"Animal study in mice using antibody injection, which is an indirect approach. The antibodies may not completely neutralize all released peptide. Only two pain tests were used."},{"rthcId":"RPEP-00139","title":"Distribution of dynorphin B and methionine-enkephalin in the mouse hippocampus: influence of genotype.","authors":"van Daal, J H; Zanderink, H E; Jenks, B G; van Abeelen, J H","year":1989,"journal":"Neuroscience letters, 97(3), 241-4","doi":null,"pmid":"2566141","tags":["opioid-peptides","neuropeptides","neuroscience"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Dynorphin B mossy fiber terminal fields in the hippocampus vary by mouse genotype, with C57BL/6 mice having larger intra- and infrapyramidal projections than DBA/2 mice.","whyItMatters":"Genetic variation in hippocampal opioid pathway size may contribute to strain differences in learning, memory, and stress responses.","specificNumbers":"","methodology":"Immunohistochemistry for dynorphin B and met-enkephalin was performed on hippocampal sections from two inbred mouse strains (DBA/2 and C57BL/6).","limitations":"Only two mouse strains compared. The functional consequences of different projection sizes were not tested. Mouse hippocampal architecture differs from human."},{"rthcId":"RPEP-00140","title":"Participation of opiate receptors located in the nucleus tractus solitarii in the hypotension induced by alpha-methyldopa.","authors":"Van Giersbergen, P L; Roording, P; de Lang, H; de Jong, W","year":1989,"journal":"Brain research, 498(1), 154-8","doi":null,"pmid":"2551454","tags":["opioid-peptides","endorphins","cardiovascular","neuroscience"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Alpha-methyldopa's hypotensive effect requires opioid receptor activation in the NTS, specifically through beta-endorphin and not through enkephalins or dynorphin.","whyItMatters":"This revealed that a widely used blood pressure drug works partly through the brain's opioid system, connecting blood pressure regulation to natural opioid peptides.","specificNumbers":"","methodology":"Conscious rats received microinjections of naltrexone or specific opioid peptide antisera into the NTS, followed by systemic alpha-methyldopa. Blood pressure was monitored.","limitations":"Animal study using direct brain injection, which does not reflect how patients take the drug. Small study with limited statistical detail in the abstract."},{"rthcId":"RPEP-00141","title":"Possible involvement of beta endorphin(1-31) and dynorphin(1-13) in the central hypotensive mechanism of action of alpha methyldopa.","authors":"van Giersbergen, P L; Wiegant, V M; de Jong, W","year":1989,"journal":"Neuroendocrinology, 49(1), 71-9","doi":null,"pmid":"2566129","tags":["opioid-peptides","endorphins","cardiovascular","neuroscience"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Both beta-endorphin(1-31) and dynorphin(1-13), but not met-enkephalin, mediate alpha-methyldopa's central hypotensive effect. The opioid peptides must be released early in the drug's mechanism.","whyItMatters":"This refined the understanding of how blood pressure drugs use the brain's opioid system. Two different opioid peptide families cooperate to produce the drug's effect.","specificNumbers":"","methodology":"Conscious normotensive rats received intracisternal antisera against specific opioid peptides, followed by intracisternal alpha-methyldopa. Blood pressure and heart rate were measured.","limitations":"Animal study with intracisternal injection, not reflecting normal drug delivery. Only one blood pressure drug was tested. Results may not translate directly to humans."},{"rthcId":"RPEP-00142","title":"Possible involvement of brain opioid peptides in clonidine-induced hypotension in spontaneously hypertensive rats.","authors":"van Giersbergen, P L; Tierney, S A; Wiegant, V M; de Jong, W","year":1989,"journal":"Hypertension (Dallas, Tex. : 1979), 13(1), 83-90","doi":null,"pmid":"2536002","tags":["opioid-peptides","endorphins","cardiovascular","neuroscience"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Clonidine's central hypotensive mechanism involves beta-endorphin and dynorphin only in spontaneously hypertensive rats, not in normotensive Wistar-Kyoto rats.","whyItMatters":"This suggests the opioid system plays a special role in blood pressure regulation during hypertension. The mechanism is fundamentally different in normal versus high blood pressure states.","specificNumbers":"","methodology":"Conscious hypertensive and normotensive rats received intracisternal pretreatment with opioid antagonists or antisera, followed by cumulative intracisternal clonidine. Blood pressure and heart rate were measured.","limitations":"Used a specific genetic model of hypertension (SHR). Other types of hypertension may involve different mechanisms. Brain injection does not reflect clinical drug delivery."},{"rthcId":"RPEP-00143","title":"Induction of the gene encoding pro-dynorphin by experimentally induced arthritis enhances staining for dynorphin in the spinal cord of rats.","authors":"Weihe, E; Millan, M J; Höllt, V; Nohr, D; Herz, A","year":1989,"journal":"Neuroscience, 31(1), 77-95","doi":null,"pmid":"2570379","tags":["opioid-peptides","pain-management","neuroscience"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Chronic arthritis activates the prodynorphin gene in spinal cord neurons, increasing both mRNA and peptide levels. Unilateral inflammation produces changes only in the corresponding spinal quadrant.","whyItMatters":"This showed that chronic pain activates a specific gene program in the spinal cord with precise anatomical specificity. The dynorphin system is a major responder to chronic inflammation.","specificNumbers":"","methodology":"Polyarthritic and unilaterally inflamed rats were compared to controls using mRNA quantification, radioimmunoassay for dynorphin A, and immunohistochemistry for dynorphin and neo-endorphin in lumbosacral spinal cord.","limitations":"Animal study using induced arthritis. The functional significance of elevated dynorphin (analgesic or anti-analgesic) was not determined. Human spinal cord responses may differ."},{"rthcId":"RPEP-00144","title":"Effects of opiates during baroreceptor and ergoreceptor induced changes in blood pressure.","authors":"Williams, C A","year":1989,"journal":"Cardiovascular research, 23(3), 191-9","doi":null,"pmid":"2574074","tags":["opioid-peptides","endorphins","cardiovascular"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"All three opioid peptide families selectively blocked the exercise pressor reflex (ergoreceptor) without affecting the baroreceptor reflex, suggesting a specific opioid-catecholamine pathway for exercise blood pressure responses.","whyItMatters":"This shows the opioid system can selectively modify which blood pressure reflexes operate. Exercise-related blood pressure control has its own opioid-regulated pathway.","specificNumbers":"","methodology":"Anesthetized cats received opioid peptide injections into the cerebral aqueduct. Blood pressure responses to fatiguing muscle contractions and carotid occlusion were measured before and after opioid administration.","limitations":"Animal study in anesthetized cats. The doses were injected directly into the brain, not reflecting natural peptide levels. Anesthesia itself may alter cardiovascular reflexes."},{"rthcId":"RPEP-00145","title":"Prostanoids modulate opioid cerebrovascular responses in newborn pigs.","authors":"Armstead, W M; Mirro, R; Busija, D W; Leffler, C W","year":1990,"journal":"The Journal of pharmacology and experimental therapeutics, 255(3), 1083-9","doi":null,"pmid":"1979812","tags":["opioid-peptides","neuropeptides","cardiovascular","neuroscience"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Opioid peptides have differential effects on neonatal cerebral vasculature: enkephalins dilate, beta-endorphin constricts, and dynorphin switches depending on blood pressure status. All effects are prostaglandin-dependent.","whyItMatters":"In newborns, brain blood flow regulation is critical. Different opioid peptides having opposite effects on brain vessels means the opioid system can both protect and endanger the neonatal brain.","specificNumbers":"","methodology":"Closed cranial window technique in piglets measured pial arteriolar diameter changes in response to topical application of opioid peptides. Cerebrospinal fluid prostaglandins were measured.","limitations":"Animal study in piglets. The cranial window technique, while direct, involves surgical exposure. Doses applied topically may not reflect natural peptide concentrations."},{"rthcId":"RPEP-00146","title":"Effects of intracerebroventricular injection of dynorphin, leumorphin and alpha neo-endorphin on operant feeding in pigs.","authors":"Baldwin, B A; de la Riva, C; Ebenezer, I S","year":1990,"journal":"Physiology & behavior, 48(6), 821-4","doi":null,"pmid":"1982360","tags":["opioid-peptides","neuropeptides","obesity","neuroscience"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Full-length dynorphin A (1-17 or 1-13), leumorphin, and alpha-neo-endorphin induced rapid feeding in pigs. Shorter fragments were ineffective. Naloxone blocked all feeding effects.","whyItMatters":"Pigs are closer to humans than rodents in body size and feeding behavior. Demonstrating opioid-driven feeding in pigs strengthens the case that opioid peptides regulate human appetite.","specificNumbers":"","methodology":"Pigs with lateral ventricle cannulas received 200 µg injections of various opioid peptides. Food intake was measured using operant feeding panels with ad lib food and water.","limitations":"Brain injections of 200 µg are pharmacological, not physiological doses. The study used young pigs. Human feeding behavior involves many additional psychological and social factors."},{"rthcId":"RPEP-00147","title":"N-terminal degradation of low molecular weight opioid peptides in human cerebrospinal fluid.","authors":"Benter, I F; Hirsh, E M; Tuchman, A J; Ward, P E","year":1990,"journal":"Biochemical pharmacology, 40(3), 465-72","doi":null,"pmid":"1974424","tags":["opioid-peptides","neuropeptides","neuroscience"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Aminopeptidase M in human CSF degrades opioid peptides at rates inversely proportional to chain length. Met-enkephalin is degraded ~13x faster than dynorphin A.","whyItMatters":"This explains why different opioid peptides last different amounts of time in the brain. Short peptides like enkephalins have brief signals, while longer peptides persist longer.","specificNumbers":"","methodology":"Human CSF aminopeptidase activity was measured using naphthylamide substrates and radiolabeled peptides. Inhibitor profiles, kinetics, and chain-length dependence were characterized.","limitations":"In-vitro study of CSF enzyme activity. Actual opioid peptide lifetimes in living brain tissue depend on many additional factors beyond CSF aminopeptidase."},{"rthcId":"RPEP-00148","title":"Stimulation of hypothalamic opioid peptide release by lithium is mediated by opioid autoreceptors: evidence from a combined in vitro, ex vivo study.","authors":"Burns, G; Herz, A; Nikolarakis, K E","year":1990,"journal":"Neuroscience, 36(3), 691-7","doi":null,"pmid":"2172862","tags":["opioid-peptides","endorphins","neuroscience","peptide-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Lithium releases all three opioid peptides by inhibiting autoreceptors. Chronic treatment permanently inactivates dynorphin and met-enkephalin autoreceptors through G-protein-dependent mechanisms.","whyItMatters":"This may partly explain how lithium stabilizes mood. By releasing opioid peptides and changing their regulation, lithium could affect mood, pain perception, and stress responses.","specificNumbers":"","methodology":"Rat hypothalamic slices were perfused with lithium and/or naloxone. Opioid peptide release was measured. Tetrodotoxin confirmed presynaptic action. Pertussis toxin tested G-protein involvement.","limitations":"In-vitro hypothalamic slice study. Lithium concentrations used may not match therapeutic blood levels. The clinical significance of opioid release for bipolar disorder treatment is speculative."},{"rthcId":"RPEP-00149","title":"Immunohistochemistry of opioid peptides in the guinea pig endocrine pancreas.","authors":"Cetin, Y","year":1990,"journal":"Cell and tissue research, 259(2), 313-9","doi":null,"pmid":"1970950","tags":["opioid-peptides","neuropeptides","diabetes","metabolic-peptides"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"All three opioid peptide families are present in the guinea pig endocrine pancreas but in different cell types, with processing pathways distinct from other organs.","whyItMatters":"Finding all three opioid families in specific pancreatic cell types suggests opioid peptides play a coordinated role in regulating insulin and glucagon release.","specificNumbers":"","methodology":"Semi-thin serial sections of guinea pig pancreas were stained by peroxidase-anti-peroxidase technique with enzyme pretreatment to unmask hidden epitopes.","limitations":"Animal study in guinea pig. The functional significance of these peptides in pancreatic hormone regulation was not tested. Human pancreatic opioid distribution may differ."},{"rthcId":"RPEP-00150","title":"Phytohemagglutin-stimulated human T cell: prothymosin alpha as an accessory signal.","authors":"Cordero, O J; Sarandeses, C S; Nogueira, M","year":1990,"journal":"Journal of biological regulators and homeostatic agents, 4(1), 7-12","doi":null,"pmid":"2399834","tags":["thymosin-alpha-1","immune-function","peptide-signaling"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Prothymosin alpha acts as an accessory signal for T cell activation. It requires macrophage-derived IL-1 for its effect and works through an IL-2-dependent pathway.","whyItMatters":"This clarified how thymosin peptides boost immunity. They do not activate T cells on their own but amplify the response when other immune signals are present.","specificNumbers":"","methodology":"Human PBMC and purified T cells were cultured with prothymosin alpha, thymosin alpha 1, or thymosin beta 4. Proliferation was measured by thymidine incorporation. IL-2 receptor blocking antibodies and monocyte depletion/repletion experiments defined the mechanism.","limitations":"In-vitro study with human cells. The concentrations tested may not reflect levels achievable in patients. Only PHA stimulation was tested."},{"rthcId":"RPEP-00151","title":"Peptides on phage: a vast library of peptides for identifying ligands.","authors":"Cwirla, S E; Peters, E A; Barrett, R W; Dower, W J","year":1990,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 87(16), 6378-82","doi":null,"pmid":"2201029","tags":["phage-display","peptide-discovery"],"studyType":"laboratory-study","evidenceStrength":"high","keyFinding":"Researchers constructed a library of 300 million different hexapeptides (6-amino-acid peptides) displayed on the surface of bacteriophage (viruses that infect bacteria). They screened this massive library against a monoclonal antibody specific for beta-endorphin and, through three rounds of panning (affinity selection), isolated 51 clones that bound the antibody.\n\nAll 51 clones had tyrosine as their first amino acid, and 48 had glycine as the second — matching the known N-terminal sequence of beta-endorphin (Tyr-Gly-Gly-Phe). Binding affinities of synthesized peptides ranged from 0.35 μM to 8.3 μM.\n\nCritically, the researchers identified these binding peptides with no prior knowledge of what the antibody recognized, demonstrating that phage display could discover ligands for any receptor in a completely unbiased way.","whyItMatters":"This 1990 paper is one of the foundational studies that launched phage display peptide libraries — a technology that has since revolutionized drug discovery, earned a Nobel Prize (2018, George Smith), and enabled the development of antibodies, peptide drugs, and diagnostics across virtually every area of medicine. It demonstrated that you could find needle-in-a-haystack peptide ligands from libraries of hundreds of millions of candidates.","specificNumbers":"3 × 10⁸ recombinants · 51 binding clones isolated · All 51 had N-terminal Tyr · Binding affinities: 0.35–8.3 μM · 3 rounds of panning","methodology":"Constructed a phage display library by cloning randomly synthesized oligonucleotides into the gene III of fd phage, producing millions of hexapeptides displayed on the phage coat protein pIII. The library was screened against monoclonal antibody 3-E7 (specific for beta-endorphin N-terminus) using panning — repeated cycles of binding, washing, and elution. Selected clones were sequenced and six peptides were chemically synthesized for binding affinity measurement.","limitations":"Limited to hexapeptides (6 amino acids), which restricts the structural diversity of ligands. Binding affinities of selected peptides (μM range) were much weaker than the known high-affinity ligand (7.1 nM). Only one target antibody was tested. The technique as described identifies binders but not necessarily functional agonists or antagonists."},{"rthcId":"RPEP-00152","title":"Expression of vasopressin and opiates but not of oxytocin genes studied by in situ hybridization in embryonic rat brain primary cultures.","authors":"Di Scala-Guenot, D; Strosser, M T; Felix, J M; Richard, P","year":1990,"journal":"Brain research. Developmental brain research, 56(1), 35-9","doi":null,"pmid":"1980642","tags":["opioid-peptides","neuropeptides","neuroscience"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Prodynorphin and proenkephalin genes are expressed in 16-day embryonic rat brain cultures, earlier than previously known. This is the first evidence of early opioid gene expression in the developing nervous system.","whyItMatters":"If opioid peptide genes are active this early, opioid peptides may play roles in brain development beyond their known functions in pain and mood. They could guide nerve growth or circuit formation.","specificNumbers":"","methodology":"In situ hybridization was used to detect mRNA for vasopressin, oxytocin, prodynorphin, and proenkephalin in serum-free primary cultures from embryonic day 16 rat brain.","limitations":"In-vitro culture study. Gene expression in culture may not perfectly reflect what happens in the developing brain in vivo. Only one time point and embryonic age were tested."},{"rthcId":"RPEP-00153","title":"Formation of [Leu5]enkephalin from dynorphin A(1-8) by rat central nervous tissue in vitro.","authors":"Dixon, D M; Traynor, J R","year":1990,"journal":"Journal of neurochemistry, 54(4), 1379-85","doi":null,"pmid":"1968961","tags":["opioid-peptides","neuropeptides","neuroscience"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Dynorphin A(1-8) is extensively converted to leu-enkephalin by metalloendopeptidase EC 3.4.24.15 across all brain regions, effectively switching opioid signaling from kappa to delta receptors.","whyItMatters":"This shows the brain can actively convert one opioid signal into another. A kappa-receptor signal (dynorphin) becomes a delta-receptor signal (enkephalin), switching the type of opioid effect.","specificNumbers":"","methodology":"Radiolabeled dynorphin A(1-8) was incubated with rat brain tissue. Products were identified by HPLC. Enzyme characteristics were determined using specific inhibitors and substrates of varying length.","limitations":"In-vitro tissue study. The enzyme's actual contribution in living brain tissue, where many enzymes compete, is unknown. High doses of peptidase inhibitors were needed."},{"rthcId":"RPEP-00154","title":"Thymosin alpha 1 and thymosin beta 4 modulate human colonic lamina propria lymphocyte function.","authors":"Elitsur, Y; Mutchnick, M G; Sakr, W A; Luk, G D","year":1990,"journal":"Immunopharmacology, 20(2), 89-96","doi":null,"pmid":"2266003","tags":["thymosin-alpha-1","immune-function","gut-health"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Both thymosin alpha 1 and thymosin beta 4 suppress gut lamina propria lymphocyte proliferation through a mechanism that may involve protein kinase C but not calcium flux or ornithine decarboxylase pathways.","whyItMatters":"Gut immunity must be carefully regulated to avoid attacking food and beneficial bacteria. Thymosin peptides may help maintain this balance by dampening excessive immune responses in the gut.","specificNumbers":"","methodology":"Lamina propria lymphocytes from 18 human colon specimens were cultured with thymosin peptides. Proliferation was measured by thymidine incorporation. ODC activity was also measured.","limitations":"In-vitro study. The suppressive effect on gut immune cells contrasts with the enhancing effect on blood T cells, suggesting tissue-specific actions that need further study."},{"rthcId":"RPEP-00155","title":"Spinal dynorphin A (1-17): possible mediator of antianalgesic action.","authors":"Fujimoto, J M; Arts, K S; Rady, J J; Tseng, L F","year":1990,"journal":"Neuropharmacology, 29(7), 609-17","doi":null,"pmid":"1974711","tags":["opioid-peptides","pain-management","neuroscience"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Dynorphin A(1-17) mediates an antianalgesic (pain-relief-opposing) system in the spinal cord. Most analgesics activate both pain relief and this dynorphin-mediated opposition simultaneously.","whyItMatters":"This challenges the view that all opioid peptides are painkillers. Dynorphin A can oppose pain relief, which means the body has a built-in system that limits how much pain relief any drug can provide.","specificNumbers":"","methodology":"Mice received intrathecal dynorphin antibodies followed by intracerebroventricular analgesic drugs. Pain was measured by tail-flick response. Multiple analgesic types were tested.","limitations":"Animal study in mice using spinal and brain injections. The very small doses active in the antianalgesic effect are unusual and the mechanism is not fully understood."},{"rthcId":"RPEP-00156","title":"Systemic single dose morphine pretreatment desensitizes mice to the spinal antianalgesic action of dynorphin A (1-17).","authors":"Fujimoto, J M; Holmes, B","year":1990,"journal":"The Journal of pharmacology and experimental therapeutics, 254(1), 1-7","doi":null,"pmid":"1973192","tags":["opioid-peptides","pain-management","neuroscience"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Single-dose morphine pretreatment desensitizes the spinal antianalgesic dynorphin system for up to 18 hours, possibly by triggering dynorphin release that leads to receptor desensitization.","whyItMatters":"This suggests morphine has two phases of action: immediate pain relief plus a delayed enhancement of relief by disabling the body's anti-pain brake. Understanding this could improve pain treatment strategies.","specificNumbers":"","methodology":"Mice received subcutaneous morphine or intrathecal dynorphin hours before testing. Dynorphin A's antianalgesic effect was then tested against multiple intracerebroventricular analgesics using the tail-flick test.","limitations":"Animal study in mice using high morphine doses. The desensitization mechanism is proposed but not directly proven. Human translation is uncertain."},{"rthcId":"RPEP-00157","title":"Regulation of dopamine release in vitro from the posterior pituitary by opioid peptides.","authors":"Garris, P A; Ben-Jonathan, N","year":1990,"journal":"Neuroendocrinology, 52(4), 399-404","doi":null,"pmid":"1979840","tags":["opioid-peptides","neuropeptides","neuroscience"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Endogenous opioid peptides tonically inhibit dopamine release from both pituitary regions. Opioid peptides show differential potency between the two regions, suggesting different receptor distributions.","whyItMatters":"Dopamine from the pituitary regulates prolactin and other hormones. Different opioid regulation in different pituitary regions adds precision to hormonal control.","specificNumbers":"","methodology":"Posterior pituitary and stalk-median eminence from ovariectomized rats were incubated in vitro. Potassium-evoked dopamine release was measured by HPLC after exposure to opioid peptides and naloxone.","limitations":"In-vitro study using isolated tissue. The artificial potassium stimulation does not perfectly mimic natural nerve signaling. Only one species and one hormonal condition (ovariectomized) were tested."},{"rthcId":"RPEP-00158","title":"Enkephalins modulate inhibitory neuromuscular transmission in circular muscle of human colon via delta-opioid receptors.","authors":"Hoyle, C H; Kamm, M A; Burnstock, G; Lennard-Jones, J E","year":1990,"journal":"The Journal of physiology, 431, 465-78","doi":null,"pmid":"1966052","tags":["opioid-peptides","gut-health","neuroscience"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Enkephalins inhibit non-adrenergic, non-cholinergic inhibitory neurotransmission in human colon through prejunctional delta-opioid receptors with high selectivity.","whyItMatters":"This explains one mechanism by which opioids cause constipation. By blocking the nerve signals that normally relax the colon, opioid peptides reduce colon movement.","specificNumbers":"","methodology":"Sucrose-gap technique measured electrical responses in human colon circular muscle. Multiple opioid agonists and antagonists were tested to determine receptor selectivity.","limitations":"In-vitro study using human tissue. The isolated tissue preparation removes normal neural network activity. Only one region of the colon was studied."},{"rthcId":"RPEP-00159","title":"Trophic effects of enkephalin, beta-endorphine and dynorphine on ventral spinal cord in culture.","authors":"Iwasaki, Y; Kinoshita, M; Ikeda, K; Shiojima, T","year":1990,"journal":"The International journal of neuroscience, 50(3-4), 131-5","doi":null,"pmid":"1979964","tags":["opioid-peptides","neuropeptides","neuroscience"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Enkephalin, beta-endorphin, and dynorphin are not growth factors for ventral spinal cord neurons. They did not affect neurite extension or glial cell proliferation in embryonic cultures.","whyItMatters":"This negative result is informative. Despite opioid peptide genes being active early in development, the peptides themselves do not directly promote nerve growth in spinal cord tissue.","specificNumbers":"","methodology":"Ventral spinal cord explants from 13-14 day rat embryos were cultured with each opioid peptide. Neurite extension and glial cell numbers were measured and compared to controls.","limitations":"Only ventral spinal cord was tested. Opioid peptides might affect growth in other brain regions. The culture conditions may not capture all relevant developmental signals. Concentrations tested were not detailed."},{"rthcId":"RPEP-00160","title":"Morphine and opioid peptides selectively inhibit the non-cholinergically mediated neurogenic contraction of guinea-pig isolated bronchial muscle.","authors":"Kamikawa, Y; Shimo, Y","year":1990,"journal":"The Journal of pharmacy and pharmacology, 42(3), 214-6","doi":null,"pmid":"1696628","tags":["opioid-peptides","neuropeptides","respiratory"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Opioid peptides selectively inhibit non-cholinergic excitatory neurotransmission in airways via prejunctional receptors, with dynorphin being the most potent endogenous peptide.","whyItMatters":"Non-cholinergic nerve signaling contributes to airway constriction in asthma. If opioid peptides naturally regulate this pathway, they could be relevant to understanding and treating asthma.","specificNumbers":"","methodology":"Guinea pig bronchial strip chains were electrically stimulated. Responses to opioid peptides and direct muscle stimulants (acetylcholine, substance P) were compared.","limitations":"In-vitro study in guinea pig airways. Human airway opioid pharmacology may differ. Only electrical stimulation was used, not natural nerve reflexes."},{"rthcId":"RPEP-00161","title":"Behavioral changes induced by stressful situations: effects of enkephalins, dynorphin, and their interactions.","authors":"Katoh, A; Nabeshima, T; Kameyama, T","year":1990,"journal":"The Journal of pharmacology and experimental therapeutics, 253(2), 600-7","doi":null,"pmid":"1971017","tags":["opioid-peptides","stress-response","neuroscience"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Enkephalin and dynorphin systems have opposing effects on stress behavior. The dynorphin system selectively interacts with the met-enkephalin system but not the leu-enkephalin system.","whyItMatters":"This shows the opioid system has both stress-reducing and stress-amplifying arms. The balance between enkephalin and dynorphin signaling may determine how well an individual copes with stress.","specificNumbers":"","methodology":"Rats received intracerebroventricular opioid peptide injections. Two behavioral tests measured stress responses: conditioned suppression of motility and forced swim immobility.","limitations":"Animal study using brain-injected synthetic analogs at pharmacological doses. Natural stress responses involve complex interactions beyond just two peptide systems."},{"rthcId":"RPEP-00162","title":"The occurrence and receptor specificity of endogenous opioid peptides within the pancreas and liver of the rat. Comparison with brain.","authors":"Khawaja, X Z; Green, I C; Thorpe, J R; Titheradge, M A","year":1990,"journal":"The Biochemical journal, 267(1), 233-40","doi":null,"pmid":"1970240","tags":["opioid-peptides","endorphins","diabetes","metabolic-peptides"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Pancreas and liver contain substantial opioid peptide levels exceeding brain content, with functional delta and kappa receptors on pancreatic islets. These peripheral opioids could regulate blood glucose.","whyItMatters":"This proved that opioid peptides are not just brain chemicals. The pancreas has its own opioid system that likely helps regulate insulin, glucagon, and blood sugar levels.","specificNumbers":"","methodology":"Radioligand displacement assays for receptor-active opioids, radioimmunoassay for specific peptides, radioligand binding for receptor subtypes, and immunogold electron microscopy for cellular localization.","limitations":"Animal study in rats. The functional role of these peripheral opioids was not directly tested. The liver had peptides but no detectable receptors, leaving its opioid function unclear."},{"rthcId":"RPEP-00163","title":"Thymosin alpha 1 modulates the expression of high affinity interleukin-2 receptors on normal human lymphocytes.","authors":"Leichtling, K D; Serrate, S A; Sztein, M B","year":1990,"journal":"International journal of immunopharmacology, 12(1), 19-29","doi":null,"pmid":"2303316","tags":["thymosin-alpha-1","immune-function","peptide-signaling"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Thymosin alpha 1 increases high-affinity IL-2 receptor expression with a bimodal dose-response pattern. This directly correlates with enhanced IL-2 production and is only effective during immune activation.","whyItMatters":"IL-2 receptor expression is a key control point for immune activation. By increasing these receptors, thymosin alpha 1 makes T cells more responsive to immune signals.","specificNumbers":"","methodology":"Human peripheral blood lymphocytes were stimulated with PHA in the presence of various thymosin alpha 1 concentrations. High-affinity IL-2 receptor numbers and affinity were measured by Scatchard analysis. Tac antigen was measured by flow cytometry.","limitations":"In-vitro study. The bimodal dose-response is unusual and varied between donors, making clinical dosing predictions difficult. Only PHA stimulation was tested."},{"rthcId":"RPEP-00164","title":"Opioid and nicotine receptors affect growth regulation of human lung cancer cell lines.","authors":"Maneckjee, R; Minna, J D","year":1990,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 87(9), 3294-8","doi":null,"pmid":"2159143","tags":["opioid-peptides","endorphins","peptide-drug-development","cancer"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Lung cancer cells have an opioid-based growth suppression system that nicotine can override. All three opioid receptor types participate, and the cancer cells produce their own opioid peptides.","whyItMatters":"This suggests the body has a natural opioid-based defense against lung cancer growth that smoking disables. It provides a biological mechanism linking smoking to accelerated cancer progression.","specificNumbers":"","methodology":"Receptor binding with specific radioligands, cAMP measurements, in vitro growth assays with opioid agonists and nicotine, and immunohistochemistry for opioid peptides in lung cancer cell lines.","limitations":"In-vitro study using cell lines. In vivo tumor biology involves many additional factors. The opioid growth inhibition effect needs confirmation in animal models and human tumors."},{"rthcId":"RPEP-00165","title":"Peptide opioids and morphine effects on inflammatory process.","authors":"Mazzone, A; Ricevuti, G; Pasotti, D; Fioravanti, A; Marcoli, M; Lecchini, S; Notario, A; Frigo, G M","year":1990,"journal":"Inflammation, 14(6), 717-26","doi":null,"pmid":"1982531","tags":["opioid-peptides","immune-function","inflammation"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Morphine has anti-inflammatory effects on granulocytes through both opioid receptor-dependent (aggregation, ATP) and independent (arachidonic acid metabolism) mechanisms. Natural opioid peptides do not share these effects.","whyItMatters":"This dissociation between morphine and natural opioid peptides suggests morphine has unique anti-inflammatory properties not shared by the body's own opioid peptides.","specificNumbers":"","methodology":"Human granulocytes were tested for aggregation, ATP release, and inflammatory lipid production in response to morphine, opioid peptides, and naloxone.","limitations":"In-vitro study. Only three opioid peptides tested. The non-opioid-receptor mechanism of morphine's effect on arachidonic acid metabolism is not explained."},{"rthcId":"RPEP-00166","title":"Specific binding of beta-endorphin to the isolated renal basolateral membranes in vitro.","authors":"Sato, H; Takeda, K; Terasaki, T; Tsuji, A","year":1990,"journal":"Chemical & pharmaceutical bulletin, 38(12), 3395-9","doi":null,"pmid":"2092936","tags":["opioid-peptides","endorphins","kidney"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Beta-endorphin binds to kidney membranes through both opioid (high-affinity, low-capacity) and non-opioid (low-affinity, high-capacity) sites. The non-opioid binding involves the mid-portion of the peptide.","whyItMatters":"Beta-endorphin affects kidney function, and most of this may work through non-opioid mechanisms. This is important for understanding how opioid drugs affect kidney function.","specificNumbers":"","methodology":"Radioiodinated beta-endorphin binding to rat renal basolateral membranes was characterized by saturation isotherms, competition with naloxone and other opioid peptides, and Scatchard analysis.","limitations":"In-vitro binding study. The functional consequences of non-opioid binding in the kidney were not tested. Only one species was examined."},{"rthcId":"RPEP-00167","title":"Searching for peptide ligands with an epitope library.","authors":"Scott, J K; Smith, G P","year":1990,"journal":"Science (New York, N.Y.), 249(4967), 386-90","doi":null,"pmid":"1696028","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00168","title":"Changes in the processing of pro-dynorphin end products in the substantia nigra during neonatal development.","authors":"Sei, C A; Dores, R M","year":1990,"journal":"Peptides, 11(1), 89-94","doi":null,"pmid":"2342993","tags":["opioid-peptides","neuropeptides","neuroscience"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Prodynorphin processing matures much faster in the substantia nigra (day 7) than the pituitary (day 21). Late-developing conversion of dynorphin products to leu-enkephalin changes the enkephalin ratio in adults.","whyItMatters":"Different brain regions mature their opioid processing systems at different rates. The substantia nigra's early maturation makes sense because it controls movement, which develops quickly after birth.","specificNumbers":"","methodology":"Substantia nigra was dissected from rats at neonatal days 0, 7, 14, and adult. Five prodynorphin peptides plus met-enkephalin and leu-enkephalin were measured by radioimmunoassay with gel filtration chromatography.","limitations":"Animal study tracking developmental changes. Only one brain region was fully characterized. The functional consequences of different maturation rates were not tested."},{"rthcId":"RPEP-00169","title":"High density of zinc-containing and dynorphin B- and substance P-immunoreactive terminals in the marginal division of the rat striatum.","authors":"Shu, S Y; McGinty, J F; Peterson, G M","year":1990,"journal":"Brain research bulletin, 24(2), 201-5","doi":null,"pmid":"1691046","tags":["opioid-peptides","neuropeptides","neuroscience"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"The marginal division of the striatum has higher densities of zinc, dynorphin B-immunoreactive terminals, and substance P-immunoreactive terminals compared to the rest of the striatum.","whyItMatters":"Discovering a distinct opioid peptide-rich subdivision of the striatum suggests it may have specific functions in movement, motivation, or emotional processing that differ from the rest of the striatum.","specificNumbers":"","methodology":"Histological zinc staining and immunohistochemistry for dynorphin B and substance P were performed on rat brain sections through the striatum.","limitations":"Anatomical study showing higher density but not functional significance. Only three markers were examined. The marginal division's function remains unknown."},{"rthcId":"RPEP-00170","title":"The effects of opioid peptides on dopamine release in the nucleus accumbens: an in vivo microdialysis study.","authors":"Spanagel, R; Herz, A; Shippenberg, T S","year":1990,"journal":"Journal of neurochemistry, 55(5), 1734-40","doi":null,"pmid":"1976759","tags":["opioid-peptides","neuropeptides","neuroscience"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Mu and delta opioids increase, while kappa opioids decrease, dopamine release in the nucleus accumbens. This differential modulation explains their opposing motivational effects.","whyItMatters":"This provided direct neurochemical evidence for why different opioid types produce opposite emotional effects. Mu/delta activation drives reward-seeking; kappa activation drives avoidance.","specificNumbers":"","methodology":"In vivo microdialysis in anesthetized rats measured dopamine and metabolites in the nucleus accumbens after intracerebroventricular injection of selective opioid agonists. Specific antagonists confirmed receptor selectivity.","limitations":"Study done in anesthetized rats, which may alter dopamine dynamics. Intracerebroventricular injection is not region-specific. Only one dose of each agonist was detailed."},{"rthcId":"RPEP-00171","title":"Opioid-like immunoreactive neurons in secretomotor pathways of the guinea-pig ileum.","authors":"Steele, P A; Costa, M","year":1990,"journal":"Neuroscience, 38(3), 771-86","doi":null,"pmid":"2270143","tags":["opioid-peptides","neuropeptides","gut-health"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"All submucous neurons in guinea pig ileum are immunoreactive for prodynorphin peptides. Multiple distinct populations of opioid neurons with different neurochemical codes project to secretory pathways.","whyItMatters":"The ubiquitous presence of dynorphin in gut secretory neurons means the opioid system is deeply embedded in digestive control, not just an occasional modulator.","specificNumbers":"","methodology":"Combined immunohistochemistry for multiple opioid peptides and neuronal markers on whole mount preparations and sections of guinea pig ileum, with retrograde tracing to map projections.","limitations":"Animal study in guinea pig. Human gut innervation may differ. Immunoreactivity does not prove functional peptide release. Only the ileum was studied."},{"rthcId":"RPEP-00172","title":"Opioids from immunocytes interact with receptors on sensory nerves to inhibit nociception in inflammation.","authors":"Stein, C; Hassan, A H; Przewłocki, R; Gramsch, C; Peter, K; Herz, A","year":1990,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 87(15), 5935-9","doi":null,"pmid":"1974052","tags":["opioid-peptides","endorphins","immune-function","pain-management","inflammation"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Immune cells in inflamed tissue release opioid peptides that activate receptors on sensory nerve terminals, producing local pain relief. This represents a newly discovered neuroimmune analgesic pathway.","whyItMatters":"This revealed that the immune system can directly reduce pain at inflammation sites. It is a natural local painkilling mechanism that does not involve the brain.","specificNumbers":"","methodology":"Rats with hind paw inflammation were subjected to cold water swim stress. Local opioid content in immune cells, opioid receptors on nerves, and effects of local antibody injections and cyclosporine were tested.","limitations":"Animal study using an acute inflammation model. The specific immune cell types and opioid peptides involved were not fully characterized. Translation to chronic pain conditions is uncertain."},{"rthcId":"RPEP-00173","title":"Differentiation of acupuncture and nonacupuncture points by difference of associated opioids in the spinal cord in production of analgesia by acupuncture and nonacupuncture point stimulation, and relations between sodium and those opioids.","authors":"Takeshige, C; Luo, C P; Hishida, F; Igarashi, O","year":1990,"journal":"Acupuncture & electro-therapeutics research, 15(3-4), 193-209","doi":null,"pmid":"1982042","tags":["opioid-peptides","pain-management","neuroscience"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Acupuncture and non-acupuncture point stimulation produce analgesia through distinct opioid systems: met-enkephalin/mu pathway for acupuncture points, dynorphin/kappa pathway for non-acupuncture points.","whyItMatters":"This provides a biological explanation for why acupuncture point specificity matters. Different points activate genuinely different opioid peptide systems in the spinal cord and brainstem.","specificNumbers":"","methodology":"Rats received intrathecal opioid antisera and selective antagonists. Acupuncture and non-acupuncture point stimulation were tested with evoked potentials in brainstem and tail-flick analgesia. Adrenalectomy and sodium replacement experiments tested modifying conditions.","limitations":"Animal study in rats. The distinction between acupuncture and non-acupuncture points may not translate directly to human clinical practice. The sodium dependency is unusual and unexplained."},{"rthcId":"RPEP-00174","title":"Hemodynamic responses of conscious rats following intrathecal injections of prodynorphin-derived opioids: independence of action of intrathecal arginine vasopressin.","authors":"Thornhill, J A; Pittman, Q J","year":1990,"journal":"Canadian journal of physiology and pharmacology, 68(2), 174-82","doi":null,"pmid":"1968777","tags":["opioid-peptides","neuropeptides","cardiovascular"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Spinal dynorphin A raises blood pressure through kappa opioid receptors independently from vasopressin. Chain length of at least 13 amino acids is required for the cardiovascular effect.","whyItMatters":"The spinal cord's opioid system can directly influence blood pressure. This is important for understanding cardiovascular effects of spinal anesthesia and opioid medications.","specificNumbers":"","methodology":"Conscious rats with spinal catheters received intrathecal injections of prodynorphin peptides, vasopressin, and their antagonists. Blood pressure and heart rate were monitored via femoral artery catheters.","limitations":"Animal study with spinal injections at pharmacological doses. The doses used may exceed natural dynorphin levels in the spinal cord. Only one spinal level was tested."},{"rthcId":"RPEP-00175","title":"Regulation of striatonigral prodynorphin peptides by dopaminergic agents.","authors":"Trujillo, K A; Day, R; Akil, H","year":1990,"journal":"Brain research, 518(1-2), 244-56","doi":null,"pmid":"1975215","tags":["opioid-peptides","neuropeptides","neuroscience"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Both amphetamine (dopamine agonist) and haloperidol (dopamine antagonist) significantly altered levels of prodynorphin peptides in the striatum, substantia nigra, and hippocampus.","whyItMatters":"Understanding how dopamine regulates the dynorphin system is important because both systems are involved in reward, movement, and pain — and their interaction has implications for conditions like addiction and Parkinson's disease.","specificNumbers":"","methodology":"Rats received D-amphetamine sulfate or haloperidol across multiple treatment schedules and doses. Three brain regions (striatum, substantia nigra, hippocampus) were then dissected and analyzed by radioimmunoassay for five prodynorphin peptides.","limitations":"Animal study using rats with pharmacological manipulation. Drug doses and schedules may not reflect physiological conditions. No human data provided."},{"rthcId":"RPEP-00176","title":"All-D amino acid-containing channel-forming antibiotic peptides.","authors":"Wade, D; Boman, A; Wåhlin, B; Drain, C M; Andreu, D; Boman, H G; Merrifield, R B","year":1990,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 87(12), 4761-5","doi":null,"pmid":"1693777","tags":["antimicrobial-peptides","peptide-drug-development","peptide-structure","infectious-disease"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"D-enantiomers of cecropin A, magainin 2, and melittin retained equivalent antibacterial and channel-forming activity, confirming a non-receptor-mediated membrane disruption mechanism.","whyItMatters":"This finding opened the door to developing D-amino acid antimicrobial peptides that would resist enzymatic degradation in the body, potentially creating longer-lasting antibiotic treatments.","specificNumbers":"","methodology":"Researchers chemically synthesized D-enantiomers of five antimicrobial peptides, verified their mirror-image structure via circular dichroism, and tested antibacterial activity and membrane channel formation in vitro.","limitations":"In vitro study only. The practical pharmacological advantages of D-amino acid antimicrobial peptides (stability, bioavailability) were not tested in living organisms."},{"rthcId":"RPEP-00177","title":"Stimulation of endogenous opioid release displaces mu receptor binding in rat hippocampus.","authors":"Wagner, J J; Caudle, R M; Neumaier, J F; Chavkin, C","year":1990,"journal":"Neuroscience, 37(1), 45-53","doi":null,"pmid":"1978741","tags":["opioid-peptides","neuropeptides","neuroscience"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Physiological-like high-frequency stimulation of opioid-containing pathways releases detectable amounts of endogenous opioids in hippocampal slices. The release is pathway-specific and frequency-dependent.","whyItMatters":"This shows that opioid peptides are actually released during the type of nerve activity that occurs during learning and memory, supporting a functional role in hippocampal information processing.","specificNumbers":"","methodology":"Hippocampal slices were electrically stimulated at various intensities and frequencies. Displacement of [3H]DAGO from mu receptors was measured by autoradiography. Calcium dependence and pathway specificity were tested.","limitations":"In-vitro slice preparation with artificial stimulation. Natural brain activity patterns are more complex. Only mu receptor displacement was measured; delta and kappa contributions were not assessed."},{"rthcId":"RPEP-00178","title":"The immunostaining for the hypothalamic vasoactive intestinal peptide, but not for beta-endorphin, dynorphin-A or methionine-enkephalin, is affected by the glucocorticoid milieu in the rat: correlation with the prolactin secretion.","authors":"Watanobe, H","year":1990,"journal":"Regulatory peptides, 28(3), 301-11","doi":null,"pmid":"1974081","tags":["opioid-peptides","endorphins","neuropeptides","neuroscience"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Glucocorticoids regulate hypothalamic VIP expression and prolactin secretion but do not affect beta-endorphin, dynorphin A, or met-enkephalin immunostaining in the hypothalamus.","whyItMatters":"This negative result is important. It shows that despite the connections between stress hormones and the opioid system, cortisol levels do not directly control opioid peptide production in key brain areas.","specificNumbers":"","methodology":"Male rats underwent adrenalectomy or dexamethasone treatment. Hypothalamic immunostaining for VIP, beta-endorphin, dynorphin A, and met-enkephalin was quantified. Serum prolactin was measured.","limitations":"Only immunostaining intensity was measured, not peptide release or gene expression. Staining may not be sensitive enough to detect subtle changes. Only the hypothalamus was examined."},{"rthcId":"RPEP-00179","title":"Apocarboxypeptidase B-sepharose: a specific adsorbent for peptides.","authors":"Yasuhara, T; Ohashi, A","year":1990,"journal":"Biochemical and biophysical research communications, 166(1), 330-5","doi":null,"pmid":"2302209","tags":["opioid-peptides","neuropeptides","peptide-structure"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Apocarboxypeptidase B-Sepharose selectively adsorbs opioid peptides with C-terminal basic residues, providing a novel separation tool for peptide processing research.","whyItMatters":"This tool allows researchers to separate opioid peptide processing intermediates from final products, helping track how the body converts precursor proteins into active peptides.","specificNumbers":"","methodology":"Carboxypeptidase B was immobilized on Sepharose and inactivated with o-phenanthroline. Opioid peptide binding was tested at various pH values and peptides were eluted at pH 4.0.","limitations":"Technical methodology paper. The column's utility for complex biological samples was not fully demonstrated. Only a few peptides were tested."},{"rthcId":"RPEP-00180","title":"Naltrexone-sensitizing effects of centrally administered morphine and opioid peptides.","authors":"Adams, J U; Holtzman, S G","year":1991,"journal":"European journal of pharmacology, 193(1), 67-73","doi":null,"pmid":"1675608","tags":["opioid-peptides","neuropeptides","neuroscience"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Acute central opioid pretreatment produces rapid sensitization to naltrexone, predominantly through mu receptors. This represents an early stage of physical dependence occurring within hours.","whyItMatters":"Physical dependence on opioids begins much faster than previously thought. A single brain opioid exposure can produce measurable dependence within hours.","specificNumbers":"","methodology":"Rats on fixed-interval food schedules received intracerebroventricular opioid pretreatment. Naltrexone dose-effect curves were generated 4 hours later. Multiple selective opioid agonists were tested.","limitations":"Animal study with brain injections. The behavioral measure (lever pressing) may not directly parallel human dependence symptoms. High opioid doses were used."},{"rthcId":"RPEP-00181","title":"Stereoselective effect of morphine on antinociception and endogenous opioid peptide levels in plasma but not cerebrospinal fluid of dogs.","authors":"Adams, M L; Morris, D L; Brase, D A; Dewey, W L","year":1991,"journal":"Life sciences, 48(9), 917-24","doi":null,"pmid":"1671791","tags":["opioid-peptides","pain","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Active morphine raised blood levels of all four opioid peptides in dogs. The inactive mirror form did not. Neither form changed opioid peptide levels in brain fluid.","whyItMatters":"This study shows that morphine's ability to release opioid peptides into the blood is specific to its active form. It also suggests that morphine works in the brain through a different path than simply releasing endogenous opioids.","specificNumbers":"","methodology":"Dogs received subcutaneous injections of active or inactive morphine. Blood and brain fluid samples were collected and measured for four opioid peptides using radioimmunoassay. Pain response was tested with a tail-flick test.","limitations":"This was an animal study in dogs. The results may not translate directly to humans. Sample sizes were small. Only one dose level was tested."},{"rthcId":"RPEP-00182","title":"Opioids in cerebrospinal fluid in hypotensive newborn pigs.","authors":"Armstead, W M; Mirro, R; Busija, D W; Desiderio, D M; Leffler, C W","year":1991,"journal":"Circulation research, 68(4), 922-9","doi":null,"pmid":"1672630","tags":["opioid-peptides","cardiovascular","neuropeptides"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Hemorrhagic hypotension raised brain fluid opioid levels and caused pial artery dilation in newborn pigs. Blood pressure dropped from 63 to 33 mmHg.","whyItMatters":"This research suggests the body has a built-in protective response that releases opioid peptides during dangerously low blood pressure. These peptides may help keep brain blood flow going in newborns.","specificNumbers":"","methodology":"Newborn pigs had cranial windows placed to observe brain blood vessels. Brain fluid was collected during normal and low blood pressure. Opioid peptides were measured by radioimmunoassay and applied topically to observe vessel responses.","limitations":"Animal study in newborn pigs. The findings may not directly apply to human newborns. The study used an acute hemorrhage model that may differ from clinical scenarios."},{"rthcId":"RPEP-00183","title":"Neurogenic inflammation in airways.","authors":"Barnes, P J","year":1991,"journal":"International archives of allergy and applied immunology, 94(1-4), 303-9","doi":null,"pmid":"1718892","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00184","title":"Opioid peptides in Parkinson's disease: effects of dopamine repletion.","authors":"Baronti, F; Conant, K E; Giuffra, M; Davis, T L; Brughitta, G; Iadarola, M J; Berrettini, W H; Chase, T N; Mouradian, M M","year":1991,"journal":"Brain research, 560(1-2), 92-6","doi":null,"pmid":"1684735","tags":["opioid-peptides","neuroprotection","neuropeptides"],"studyType":"cross-sectional","evidenceStrength":"preliminary","keyFinding":"Cerebrospinal fluid MERGL levels were significantly low in Parkinson's patients after overnight medication withdrawal. Steady-state levodopa infusion did not restore them.","whyItMatters":"This study shows that Parkinson's disease affects more than just dopamine. The enkephalin system, which plays a role in movement control and pain, is also disrupted. This could help explain some symptoms that dopamine drugs do not fix.","specificNumbers":"","methodology":"Brain fluid was collected from Parkinson's patients after overnight medication withdrawal and again during intravenous levodopa infusion. MERGL levels were compared to healthy controls.","limitations":"Small sample of patients. Cross-sectional design cannot prove cause and effect. Brain fluid levels may not perfectly reflect what is happening inside specific brain regions."},{"rthcId":"RPEP-00185","title":"Effect of opioid peptides on circular muscle of canine duodenum.","authors":"Bauer, A J; Szurszewski, J H","year":1991,"journal":"The Journal of physiology, 434, 409-22","doi":null,"pmid":"1673718","tags":["opioid-peptides","gut-healing","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Met-enkephalin, leu-enkephalin, and dynorphin decreased inhibitory junction potentials in canine duodenal circular muscle via delta and mu receptors.","whyItMatters":"This study helps explain why opioid drugs cause constipation. Opioid peptides interfere with the nerve signals that tell gut muscles to relax, slowing down normal intestinal movement.","specificNumbers":"","methodology":"Dog duodenal circular muscle strips were studied in vitro using simultaneous mechanical and electrical recording. Various opioid agonists and receptor-selective drugs were applied.","limitations":"Animal study using isolated dog intestinal tissue in vitro. Conditions differ from a living animal. Results may not translate directly to human gut physiology."},{"rthcId":"RPEP-00186","title":"The effects of bilateral intranigral microinjection of selective opioid agonists on behavioral responses to noxious thermal stimuli.","authors":"Baumeister, A A","year":1991,"journal":"Brain research, 557(1-2), 136-45","doi":null,"pmid":"1660749","tags":["opioid-peptides","pain","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Mu-selective agonist DAGO injected into the substantia nigra produced antinociception comparable to the periaqueductal gray. Delta and kappa agonists had no effect.","whyItMatters":"This study identifies the substantia nigra as a key brain region for opioid pain control. Previously, most attention focused on the periaqueductal gray. Knowing that multiple brain areas contribute to pain relief could improve pain treatment strategies.","specificNumbers":"","methodology":"Rats received bilateral microinjections of selective opioid agonists into the substantia nigra. Pain was tested using tail-flick and hot-plate methods. Antagonists confirmed receptor specificity.","limitations":"Animal study in rats using direct brain injections. This invasive method is not applicable to human treatment. The substantia nigra is primarily known for movement control, and effects on motor function could confound pain testing."},{"rthcId":"RPEP-00187","title":"Mutagenic contaminants in synthetic peptides obtained by an azide coupling.","authors":"Castellino, S; de Castiglione, R; Forino, R; Galantino, M; Pulci, R","year":1991,"journal":"Mutagenesis, 6(3), 185-7","doi":null,"pmid":"1881348","tags":["peptide-safety","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Peptides synthesized by azide coupling contained mutagenic contaminants undetectable by HPLC. Switching synthesis methods or using counter-current purification eliminated the problem.","whyItMatters":"This finding reveals that standard purity testing may not catch all dangerous contaminants in synthetic peptides. It highlights the need for biological safety testing alongside chemical analysis.","specificNumbers":"","methodology":"Synthetic peptides including eledoisin were tested for mutagenicity using the Ames test (Salmonella typhimurium TA 1535). Different synthesis methods and purification approaches were compared.","limitations":"Focused on one manufacturing method (azide coupling) and one peptide (eledoisin). The specific mutagenic compounds were not fully identified. In vitro bacterial assay may not predict mammalian toxicity."},{"rthcId":"RPEP-00188","title":"Central peptidergic neurons as targets for glucocorticoid action. Evidence for the presence of glucocorticoid receptor immunoreactivity in various types of classes of peptidergic neurons.","authors":"Cintra, A; Fuxe, K; Solfrini, V; Agnati, L F; Tinner, B; Wikström, A C; Staines, W; Okret, S; Gustafsson, J A","year":1991,"journal":"The Journal of steroid biochemistry and molecular biology, 40(1-3), 93-103","doi":null,"pmid":"1683565","tags":["opioid-peptides","neuropeptides","receptor-signaling","hormone-optimization"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Glucocorticoid receptors were found in opioid peptide neurons and other peptidergic neurons, with strong regional variation across the brain.","whyItMatters":"This study reveals a direct link between the stress hormone system and the brain's peptide-producing cells. It helps explain how chronic stress can change levels of opioid peptides and other brain chemicals.","specificNumbers":"","methodology":"Double immunolabeling was used to detect both glucocorticoid receptors and various neuropeptides in rat brain sections. Multiple brain regions were examined.","limitations":"Animal study in rats. Immunolabeling shows receptor presence but not activity. Does not prove functional effects. Regional patterns in rats may differ from humans."},{"rthcId":"RPEP-00189","title":"Electrically-induced release of opioid peptides from the guinea-pig myenteric plexus preparation.","authors":"Corbett, A D; Gillan, M G; Kosterlitz, H W","year":1991,"journal":"Journal of receptor research, 11(1-4), 665-73","doi":null,"pmid":"1886085","tags":["opioid-peptides","gut-healing","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Pro-enkephalin fragments were released at 29-43% of tissue content loss. BAM-8 released at higher rates. The precursor BAM-18 was not released.","whyItMatters":"This study reveals how gut nerves process and release their own opioid peptides. Understanding this processing could help explain gut pain control and opioid-related gut disorders.","specificNumbers":"","methodology":"Guinea pig myenteric plexus-longitudinal muscle preparations were electrically stimulated in vitro. Released opioid peptides were measured in the perfusion fluid and correlated with tissue content changes.","limitations":"In vitro study using isolated guinea pig gut tissue. Electrical stimulation may not perfectly mimic natural nerve activity. Results may not apply to human gut tissue."},{"rthcId":"RPEP-00190","title":"Systemic administration of kainic acid differentially regulates the levels of prodynorphin and proenkephalin mRNA and peptides in the rat hippocampus.","authors":"Douglass, J; Grimes, L; Shook, J; Lee, P H; Hong, J S","year":1991,"journal":"Brain research. Molecular brain research, 9(1-2), 79-86","doi":null,"pmid":"1850080","tags":["opioid-peptides","neuroprotection","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Kainic acid seizures increased hippocampal prodynorphin and proenkephalin mRNA while decreasing dynorphin A and met-enkephalin peptide levels, both proportional to seizure severity.","whyItMatters":"This study shows the hippocampus has a dynamic opioid response to seizures. The brain releases stored opioid peptides (possibly to limit seizure damage) and then ramps up production. This could be part of a natural protective mechanism.","specificNumbers":"","methodology":"Rats received subcutaneous kainic acid. Seizure severity was scored. Hippocampal mRNA was measured by Northern blot; peptide levels were measured by immunoassay at multiple time points.","limitations":"Animal study in rats using a chemical seizure model. The kainic acid model may not perfectly represent human epilepsy. Only the hippocampus was studied."},{"rthcId":"RPEP-00191","title":"Up-regulation of opioid gene expression in spinal cord evoked by experimental nerve injuries and inflammation.","authors":"Draisci, G; Kajander, K C; Dubner, R; Bennett, G J; Iadarola, M J","year":1991,"journal":"Brain research, 560(1-2), 186-92","doi":null,"pmid":"1684729","tags":["opioid-peptides","pain","inflammation"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Chronic constriction injury and inflammation both upregulated spinal preprodynorphin mRNA rapidly and sustainably. Complete nerve transection and crush did not.","whyItMatters":"This study links ongoing pain signals to a specific spinal cord response -- dynorphin production. Since dynorphin can both relieve and worsen pain depending on the context, this finding is important for understanding chronic pain conditions.","specificNumbers":"","methodology":"Rats underwent sciatic nerve constriction injury, complete transection, crush, or peripheral inflammation. Spinal cord mRNA for preprodynorphin and preproenkephalin was measured at multiple time points.","limitations":"Animal study in rats. The chronic constriction injury model is an approximation of human nerve damage. Only spinal cord was examined. Dynorphin's role in pain is complex and context-dependent."},{"rthcId":"RPEP-00192","title":"Endogenous opioids tonically inhibit the depressor neurones in the caudal ventrolateral medulla of rabbits: mediation through delta- and kappa-receptors.","authors":"Drolet, G; Morilak, D A; Chalmers, J","year":1991,"journal":"Neuropharmacology, 30(4), 383-90","doi":null,"pmid":"1649420","tags":["opioid-peptides","cardiovascular","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Naloxone injection into the caudal ventrolateral medulla caused dose-dependent blood pressure drops. Delta and kappa receptor antagonists reproduced this effect; mu antagonist did not.","whyItMatters":"This study reveals that the body's natural opioid peptides play a constant role in maintaining blood pressure through the brain. This could be relevant to understanding blood pressure disorders.","specificNumbers":"","methodology":"Anesthetized rabbits received bilateral microinjections of opioid antagonists (naloxone, ICI 174864, nor-binaltorphimine, beta-funaltrexamine) into the caudal ventrolateral medulla. Blood pressure and heart rate were continuously monitored.","limitations":"Animal study in anesthetized rabbits. Anesthesia itself affects blood pressure regulation. Results may differ in conscious animals or humans."},{"rthcId":"RPEP-00193","title":"Neuropeptides and inflammatory bowel disease.","authors":"Eysselein, V E; Nast, C C","year":1991,"journal":"Zeitschrift fur Gastroenterologie. Verhandlungsband, 26, 253-7","doi":null,"pmid":"1714164","tags":["neuropeptides","gut-healing","inflammation"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"VIP is diminished in intestinal smooth muscle of Crohn's patients. Substance P receptors are markedly increased at small vessels and lymph nodules in inflamed IBD intestine.","whyItMatters":"If neuropeptides actively drive IBD symptoms like abnormal gut motility and inflammation, they could be targets for new treatments that go beyond standard immune suppression.","specificNumbers":"","methodology":"Review of studies examining gut neuropeptide content, innervation patterns, and receptor distribution in tissue from IBD patients.","limitations":"Review article summarizing available evidence as of 1991. The field was still early, and not all findings had been replicated. Neuropeptide measurement techniques were evolving."},{"rthcId":"RPEP-00194","title":"mu-receptor mediates elevated glucose and corticosterone after third ventricle injection of opioid peptides.","authors":"Gunion, M W; Rosenthal, M J; Morley, J E; Miller, S; Zib, B; Butler, B; Moore, R D","year":1991,"journal":"The American journal of physiology, 261(1 Pt 2), R70-81","doi":null,"pmid":"1677542","tags":["opioid-peptides","receptor-signaling","hormone-optimization"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Mu receptor agonists raised blood glucose and corticosterone. Delta agonist raised fatty acids only. Kappa agonist raised glucose only. Mu antagonist blocked the glucose/corticosterone effects.","whyItMatters":"This study maps out how different brain opioid receptors control metabolism. The mu receptor's ability to raise blood sugar and stress hormones has implications for understanding opioid drug side effects and stress responses.","specificNumbers":"","methodology":"Unanesthetized rats with chronic brain cannulas received third ventricle injections of four opioid agonists at multiple doses. Blood was sampled from the tail at 0, 15, 30, 60, 90, and 120 minutes.","limitations":"Animal study in rats using direct brain injections. The doses and route do not reflect normal physiology or clinical opioid use. Anesthetic-free but still invasive."},{"rthcId":"RPEP-00195","title":"Characterization of opioid-sensitive neurons in the anteroventral third ventricle region of polydipsic inbred mice in vitro.","authors":"Hattori, Y; Katafuchi, T; Koizumi, K","year":1991,"journal":"Brain research, 538(2), 283-8","doi":null,"pmid":"1672830","tags":["opioid-peptides","receptor-signaling","neuropeptides"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Morphine inhibited 44% of AV3V neurons in polydipsic STR/N mice vs. 59% in controls. All three opioid receptor types were functional in both strains.","whyItMatters":"This study links excessive drinking behavior to reduced opioid sensitivity in a specific brain region. It adds to our understanding of how the brain controls thirst and fluid intake.","specificNumbers":"","methodology":"Hypothalamic brain slices from STR/N and Swiss/Webster mice were prepared. Single neuron recordings were made while applying morphine and receptor-selective opioid agonists.","limitations":"Animal study using an inbred mouse strain that may not represent normal thirst disorders. In vitro brain slice preparation may not fully reflect in vivo conditions."},{"rthcId":"RPEP-00196","title":"Neuropeptide regulation of feeding in dogs.","authors":"Inui, A; Okita, M; Nakajima, M; Inoue, T; Sakatani, N; Oya, M; Morioka, H; Okimura, Y; Chihara, K; Baba, S","year":1991,"journal":"The American journal of physiology, 261(3 Pt 2), R588-94","doi":null,"pmid":"1716066","tags":["opioid-peptides","neuropeptides","weight-loss"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Pancreatic polypeptides and dynorphin A stimulated feeding in satiated dogs. NPY, galanin, norepinephrine, and GRH did not, despite working in rats.","whyItMatters":"Most feeding research is done in rats. This study shows that dogs use different brain peptide systems to control appetite. Since dogs are closer to humans in many ways, this matters for translating appetite research to people.","specificNumbers":"","methodology":"Satiated dogs received third ventricle injections of various neuropeptides through chronic cannulas. Food and water intake were measured over specified periods.","limitations":"Animal study in dogs. Brain injections do not reflect normal physiology. Small number of peptides tested. The dog may still differ from humans in appetite regulation."},{"rthcId":"RPEP-00197","title":"Increases in opioid-mediated swim antinociception following endopeptidase 24.15 inhibition.","authors":"Kest, B; Orlowski, M; Bodnar, R J","year":1991,"journal":"Physiology & behavior, 50(4), 843-5","doi":null,"pmid":"1663630","tags":["opioid-peptides","pain","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Central administration of an endopeptidase 24.15 inhibitor enhanced opioid-mediated swim stress antinociception. The effect was reversed by naloxone.","whyItMatters":"Instead of adding external opioids (which carry addiction risk), this approach boosts the body's own pain-relief peptides by preventing their breakdown. This could inspire new pain treatments.","specificNumbers":"","methodology":"Rats received intracerebroventricular injections of the enzyme inhibitor cFP-AAF-pAB before swim stress testing. Pain thresholds were measured before and after. Naloxone was used to confirm opioid involvement.","limitations":"Animal study in rats using brain injections. The enzyme inhibitor was given centrally, not orally. Acute stress model may not represent chronic pain. Early-stage research."},{"rthcId":"RPEP-00198","title":"Regulation of proopiomelanocortin messenger RNA concentrations by opioid peptides in primary cell cultures of rat hypothalamus.","authors":"l'Héreault, S; Barden, N","year":1991,"journal":"Brain research. Molecular brain research, 10(2), 115-21","doi":null,"pmid":"1649365","tags":["opioid-peptides","receptor-signaling","hormone-optimization"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Beta-endorphin inhibited POMC mRNA by 65% via delta receptors. Enkephalins also worked through delta receptors. Dynorphin worked through kappa. Mu receptors were not involved.","whyItMatters":"POMC produces both the stress hormone trigger ACTH and the pain-relief peptide beta-endorphin. This feedback loop means opioid peptides can turn down their own production and reduce stress hormone output.","specificNumbers":"","methodology":"Primary rat hypothalamic cell cultures were treated with opioid peptides and receptor-selective antagonists. POMC mRNA was measured to assess gene activity.","limitations":"In vitro cell culture study. Isolated cells may not behave the same as intact brain circuits. Only hypothalamic cells were studied. Receptor classification from 1991 may not fully align with current understanding."},{"rthcId":"RPEP-00199","title":"A new type of synthetic peptide library for identifying ligand-binding activity.","authors":"Lam, K S; Salmon, S E; Hersh, E M; Hruby, V J; Kazmierski, W M; Knapp, R J","year":1991,"journal":"Nature, 354(6348), 82-4","doi":null,"pmid":"1944576","tags":["peptide-libraries","drug-discovery","high-throughput-screening"],"studyType":"methods-landmark","evidenceStrength":"foundational-methodology","keyFinding":"This landmark 1991 Nature paper introduced the \"one-bead, one-peptide\" (OBOP) approach to peptide library screening. Each tiny resin bead carries millions of copies of a single unique peptide sequence, and the library contains millions of beads — each with a different peptide. This allows researchers to screen millions of peptide sequences simultaneously for binding to a target receptor, enzyme, or antibody.\n\nThe method overcame severe limitations of prior approaches: predetermined small libraries were too limited, and phage display libraries were restricted by biology. The OBOP method enabled rapid identification and sequencing of high-affinity peptide ligands from random libraries of millions of candidates.","whyItMatters":"This paper was foundational for modern peptide drug discovery. The one-bead, one-peptide concept enabled combinatorial chemistry approaches that dramatically accelerated the identification of peptides that bind to disease-relevant targets. It helped launch the field of combinatorial peptide libraries, which remains central to drug discovery more than three decades later.","specificNumbers":"Millions of unique peptides per library · One bead = one peptide sequence · Published in Nature, 1991 · Overcame limitations of phage display and predetermined libraries","methodology":"The researchers developed a split-and-mix synthesis approach on solid-phase resin beads, where each bead carries copies of a single random peptide sequence. Libraries of millions of beads (each with a unique peptide) were screened against target acceptor molecules. Positive beads were isolated and the peptide sequences determined.","limitations":"The original 1991 method was limited to linear peptides and had constraints in peptide length and chemical diversity compared to modern approaches. Screening was visual/manual, which has since been automated. The paper established the concept but the technology required decades of refinement."},{"rthcId":"RPEP-00200","title":"Evidence for enkephalin- and endorphin-immunoreactive cells in the anterior pituitary of the axolotl Ambystoma mexicanum.","authors":"Leon-Olea, M; Sanchez-Alvarez, M; Piña, A L; Bayon, A","year":1991,"journal":"The Journal of comparative neurology, 305(3), 412-20","doi":null,"pmid":"1674748","tags":["opioid-peptides","neuropeptides"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Leu-enkephalin immunoreactivity was found in many cells of the axolotl anterior pituitary, unlike mammals. Beta-endorphin distribution was similar to other vertebrates.","whyItMatters":"Finding enkephalin in pituitary cells (not just nerve fibers) in this ancient amphibian suggests the opioid system evolved differently in different lineages. It expands our understanding of how opioid peptides diversified across vertebrate evolution.","specificNumbers":"","methodology":"Immunohistochemistry using antisera against leu-enkephalin, beta-endorphin, met-enkephalin, and dynorphin A(1-8) on axolotl pituitary sections.","limitations":"Descriptive study in a single amphibian species. Immunohistochemistry shows location but not function. Antibody cross-reactivity is always a concern with evolutionary comparisons."},{"rthcId":"RPEP-00201","title":"The phylogeny of Met-enkephalin and Leu-enkephalin: studies on the holostean fish Lepisosteus platyrhincus and the Australian lungfish, Neoceratodus forsteri.","authors":"McDonald, L K; Joss, J M; Dores, R M","year":1991,"journal":"General and comparative endocrinology, 84(2), 228-36","doi":null,"pmid":"1783268","tags":["opioid-peptides","neuropeptides"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Authentic met-enkephalin and leu-enkephalin were detected in holostean fish and lungfish brains. Dynorphin-related peptides were not detected in either species.","whyItMatters":"These ancient fish sit at key points in vertebrate evolution. Finding enkephalins but not dynorphins suggests the enkephalin system is more evolutionarily ancient.","specificNumbers":"","methodology":"Brain extracts were fractionated by Sephadex G-50 chromatography and analyzed by reverse-phase HPLC with radioimmunoassay for multiple opioid peptides.","limitations":"Negative results for dynorphin could reflect low abundance rather than true absence. Detection methods from 1991 were less sensitive than modern techniques. Only two species studied."},{"rthcId":"RPEP-00202","title":"Neuropeptides.","authors":"Moore, M R; Black, P M","year":1991,"journal":"Neurosurgical review, 14(2), 97-110","doi":null,"pmid":"1870724","tags":["opioid-peptides","neuropeptides"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"32 brain peptides are categorized and reviewed across location, synthesis, receptor binding, and function, organized into opioid, pituitary hormone, and miscellaneous peptide groups.","whyItMatters":"This review provided a useful reference map of brain peptides at a time when the field was rapidly expanding. It connects peptide discovery to clinical neurosurgery.","specificNumbers":"","methodology":"Narrative review summarizing published literature on 32 neuropeptides as of 1991.","limitations":"Narrative review from 1991. Many details have been updated since. Broad scope limits depth on any single peptide system."},{"rthcId":"RPEP-00203","title":"Enkephalin hydrolysis by human serum biotinidase.","authors":"Oizumi, J; Hayakawa, K","year":1991,"journal":"Biochimica et biophysica acta, 1074(3), 433-8","doi":null,"pmid":"1679665","tags":["opioid-peptides","peptide-design","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Human serum biotinidase hydrolyzes enkephalins and dynorphin A (<10-mer) with kcat/Km values similar to its biotin substrate biocytin.","whyItMatters":"This reveals a previously unknown way the body controls opioid peptide levels in the blood. Biotinidase deficiency, a known genetic condition, might affect opioid peptide metabolism.","specificNumbers":"","methodology":"Purified human serum biotinidase was tested against various peptide substrates. Kinetic parameters (kcat, Km) were determined. Inhibition studies used various antibiotic inhibitors.","limitations":"In vitro study using purified enzyme. Conditions differ from the complex blood environment. Clinical significance of this activity is unknown."},{"rthcId":"RPEP-00204","title":"Naturally occurring opioid receptor agonists stimulate adenylate cyclase activity in rat olfactory bulb.","authors":"Onali, P; Olianas, M C","year":1991,"journal":"Molecular pharmacology, 39(4), 436-41","doi":null,"pmid":"1673223","tags":["opioid-peptides","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"All three opioid peptides stimulated adenylate cyclase in olfactory bulb by ~40% above baseline. Beta-endorphin was most potent (EC50 22 nM). Naloxone blocked all effects.","whyItMatters":"This finding challenges the assumption that opioid receptors always inhibit cell activity. In the olfactory bulb, they do the opposite, which could affect how we understand smell processing and opioid drug effects.","specificNumbers":"","methodology":"Rat olfactory bulb homogenates were treated with opioid peptides at various concentrations. Adenylate cyclase activity was measured. Naloxone antagonism confirmed receptor involvement.","limitations":"In vitro study using tissue homogenates, which disrupts normal cellular context. Only one brain region examined. Rat findings may differ from humans."},{"rthcId":"RPEP-00205","title":"Effect of opioid peptides on electrically evoked acetylcholine release from Torpedo electromotor neurons.","authors":"Oron, L; Sarne, Y; Michaelson, D M","year":1991,"journal":"Neuroscience letters, 125(2), 231-4","doi":null,"pmid":"1679220","tags":["opioid-peptides","neuropeptides","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Dynorphin A(1-8) approximately doubled acetylcholine release from Torpedo electromotor neurons. The effect was naloxone-reversible and showed strong seasonal variation.","whyItMatters":"This study shows opioid peptides can boost nerve transmission (not just inhibit it) and that this modulation follows seasonal patterns, suggesting hormonal or environmental regulation.","specificNumbers":"","methodology":"Torpedo electric organ preparations were electrically stimulated. Acetylcholine release was measured after applying opioid peptides. Experiments were conducted across seasons.","limitations":"Study in a highly specialized marine animal (electric ray). The electric organ is a unique tissue. Seasonal patterns in Torpedo may not apply to mammals."},{"rthcId":"RPEP-00206","title":"Increased methionine-enkephalin levels in genetically epileptic (tg/tg) mice.","authors":"Patel, V K; Abbott, L C; Rattan, A K; Tejwani, G A","year":1991,"journal":"Brain research bulletin, 27(6), 849-52","doi":null,"pmid":"1686215","tags":["opioid-peptides","neuroprotection","neuropeptides"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Met-enkephalin was significantly elevated in cortex, hippocampus, and brainstem of tg/tg epileptic mice. Beta-endorphin and dynorphin were unchanged.","whyItMatters":"Elevated enkephalin in seizure-prone brain regions suggests the opioid system is actively involved in epilepsy. This could help develop new anti-seizure treatments targeting opioid pathways.","specificNumbers":"","methodology":"Brain regions from 15-18 week old tg/tg and control mice were dissected. Met-enkephalin, beta-endorphin, and dynorphin levels were measured by radioimmunoassay.","limitations":"Genetic mouse model that may not represent all forms of human epilepsy. Measurements show total levels, not release rates. Cannot determine if elevated enkephalin is cause or effect of seizures."},{"rthcId":"RPEP-00207","title":"The prenatal development profile of expression of opioid peptides and receptors in the mouse brain.","authors":"Rius, R A; Barg, J; Bem, W T; Coscia, C J; Loh, Y P","year":1991,"journal":"Brain research. Developmental brain research, 58(2), 237-41","doi":null,"pmid":"1674235","tags":["opioid-peptides","neuropeptides","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"All three opioid peptide classes (enkephalin, dynorphin, endorphin) were detected in embryonic mouse brain before their putative receptors during E11.5 to P1.","whyItMatters":"If opioid peptides appear before their receptors during brain development, they may have early roles in guiding brain growth that we do not yet understand. This could have implications for how opioid drug exposure during pregnancy affects fetal brain development.","specificNumbers":"","methodology":"Mouse brains were collected at multiple embryonic time points (E11.5 to P1). Opioid peptides were measured by immunoassay and receptors by binding assays.","limitations":"Mouse developmental study that may not directly match human timing. Immunoassay detection depends on antibody sensitivity. Receptor binding assays may miss very low levels."},{"rthcId":"RPEP-00208","title":"Effects of dexfenfluramine and opioid peptides, alone or in combination, on food intake and brain serotonin turnover in rats.","authors":"Robert, J J; Orosco, M; Rouch, C; Cohen, Y; Jacquot, C","year":1991,"journal":"Pharmacology, biochemistry, and behavior, 38(4), 775-80","doi":null,"pmid":"1678525","tags":["opioid-peptides","weight-loss","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Dexfenfluramine's anorectic effect dominated over opioid agonist feeding stimulation. The interaction was not mediated by brain serotonin turnover changes.","whyItMatters":"Understanding how appetite-stimulating (opioid) and appetite-suppressing (serotonergic) systems interact is key to developing better weight loss treatments.","specificNumbers":"","methodology":"Rats received central injections of opioid agonists (beta-endorphin, dynorphin, DSLET) or naltrexone, alone or combined with d-FF. Food intake and brain serotonin turnover were measured.","limitations":"Animal study in rats with central drug administration. Doses and routes do not reflect clinical use. d-FF was later withdrawn from human use due to safety concerns."},{"rthcId":"RPEP-00209","title":"Effects of opioid be drugs on auditory evoked potentials suggest a role of lateral olivocochlear dynorphins in auditory function.","authors":"Sahley, T L; Kalish, R B; Musiek, F E; Hoffman, D W","year":1991,"journal":"Hearing research, 55(1), 133-42","doi":null,"pmid":"1684359","tags":["opioid-peptides","neuropeptides","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Kappa opioid agonists enhanced auditory nerve compound action potential amplitudes. Mu and delta agonists had no effect. Naloxone altered baseline responses.","whyItMatters":"This study identifies a specific opioid receptor type (kappa/dynorphin) in hearing function. This could be relevant to understanding hearing loss, tinnitus, and opioid drug side effects on hearing.","specificNumbers":"","methodology":"Chinchillas received intravenous opioid agonists and antagonists. Click-evoked compound action potentials (N1 and N2) were recorded at the round window of the cochlea.","limitations":"Animal study in chinchillas. Intravenous drug administration affects the whole body, not just the ear. The specific site of action (cochlear vs. central) is not definitively established."},{"rthcId":"RPEP-00210","title":"Beta-endorphin: a highly selective endogenous opioid agonist for presynaptic mu opioid receptors.","authors":"Schoffelmeer, A N; Warden, G; Hogenboom, F; Mulder, A H","year":1991,"journal":"The Journal of pharmacology and experimental therapeutics, 258(1), 237-42","doi":null,"pmid":"1677039","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00211","title":"Diethylstilbesterol- and pregnancy-induced changes in rat neurointermediate lobe oxytocin, arginine vasopressin, methionine enkephalin and dynorphin.","authors":"Schriefer, J A","year":1991,"journal":"Neuroendocrinology, 54(3), 185-91","doi":null,"pmid":"1682832","tags":["opioid-peptides","fertility","hormone-optimization"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Pregnancy and DES treatment altered pituitary met-enkephalin and dynorphin content in patterns paralleling oxytocin and vasopressin changes.","whyItMatters":"If opioid peptides regulate oxytocin release during pregnancy, this could affect labor onset, milk letdown, and maternal bonding. It also explains why opioid drugs can interfere with these processes.","specificNumbers":"","methodology":"Rat neurointermediate lobe tissue was analyzed during diestrus, after DES treatment, and at day 22 of pregnancy. Four peptides were measured for content, synthesis, and release.","limitations":"Animal study in rats. Pituitary peptide levels were measured but functional consequences not directly tested. DES (synthetic estrogen) effects may not perfectly mimic natural pregnancy hormones."},{"rthcId":"RPEP-00212","title":"Prolonged inflammatory pain modifies corticotropin-releasing factor-induced opioid peptide release in the hypothalamus.","authors":"Shippenberg, T S; Herz, A; Nikolarakis, K","year":1991,"journal":"Brain research, 563(1-2), 209-14","doi":null,"pmid":"1686211","tags":["opioid-peptides","pain","inflammation","hormone-optimization"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Chronic inflammation increased basal enkephalin release but abolished CRF-stimulated release of all three opioid peptides from the hypothalamus. KCl-stimulated release remained intact.","whyItMatters":"This shows chronic pain fundamentally changes how the brain's stress and pain systems communicate. The broken CRF-opioid link could explain stress sensitivity and poor pain coping in chronic pain patients.","specificNumbers":"","methodology":"Rats received Freund's adjuvant injection in the hindlimb. After 10 days, hypothalamic tissue was superfused in vitro. Baseline and stimulated (CRF or KCl) opioid peptide release was measured.","limitations":"Animal study using in vitro hypothalamic tissue. Freund's adjuvant creates intense inflammation that may not match all clinical pain conditions. Only one time point studied."},{"rthcId":"RPEP-00213","title":"Opiate tolerance and dependence: recent findings and synthesis.","authors":"Trujillo, K A; Akil, H","year":1991,"journal":"The New biologist, 3(10), 915-23","doi":null,"pmid":"1662985","tags":["opioid-peptides","addiction","receptor-signaling"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Opiate tolerance involves multiple mechanisms: environmental learning, NMDA receptor involvement, second messenger system adaptations, and altered intracellular signaling. Receptor numbers change minimally.","whyItMatters":"Understanding tolerance mechanisms is essential for managing pain patients who need long-term opioid therapy and for developing treatments for opioid addiction.","specificNumbers":"","methodology":"Narrative review synthesizing behavioral, cellular, and molecular studies on opiate tolerance and dependence.","limitations":"Review from 1991. Significant advances in molecular biology and genetics have since expanded our understanding. Some mechanisms discussed were still speculative at the time."},{"rthcId":"RPEP-00214","title":"Effects of PCB (Aroclor 1254) on non-specific immune parameters in rhesus (Macaca mulatta) monkeys.","authors":"Tryphonas, H; Luster, M I; White, K L; Naylor, P H; Erdos, M R; Burleson, G R; Germolec, D; Hodgen, M; Hayward, S; Arnold, D L","year":1991,"journal":"International journal of immunopharmacology, 13(6), 639-48","doi":null,"pmid":"1721612","tags":["immune-function","neuropeptides","peptide-safety"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Chronic low-dose PCB exposure increased serum complement and NK cell activity while altering other immune parameters in rhesus monkeys.","whyItMatters":"Environmental chemicals can alter immune function over time. Since many immune responses are mediated by peptides (cytokines, chemokines), this has relevance to peptide-mediated immune regulation.","specificNumbers":"","methodology":"Five groups of female rhesus monkeys received oral PCB at 0, 5, 20, 40, or 80 micrograms/kg/day. Immunotoxicity testing was performed after 55 months of exposure.","limitations":"Animal study in monkeys. PCB exposure levels and duration may not match typical human environmental exposure. Limited number of animals per group. Not a peptide-specific study."},{"rthcId":"RPEP-00215","title":"No evidence for endorphin deficiency in fibromyalgia following investigation of cerebrospinal fluid (CSF) dynorphin A and Met-enkephalin-Arg6-Phe7.","authors":"Vaerøy, Henning; Nyberg, Fred; Terenius, Lars","year":1991,"journal":"Pain, 46(2), 139-143","doi":"10.1016/0304-3959(91)90068-9","pmid":"1684241","tags":["opioid-peptides","pain"],"studyType":"cross-sectional","evidenceStrength":"moderate","keyFinding":"CSF dynorphin A (14.3 fmol/ml) and met-enkephalin-Arg-Phe (35.1 fmol/ml) were normal in fibromyalgia. No evidence of endorphin deficiency.","whyItMatters":"If fibromyalgia is not caused by an opioid peptide deficiency, this explains why opioid painkillers often do not work well for fibromyalgia. Treatment needs to target other mechanisms.","specificNumbers":"","methodology":"Cerebrospinal fluid was collected from fibromyalgia patients via lumbar puncture. Dynorphin A and met-enkephalin-Arg-Phe were measured by radioimmunoassay and correlated with previously measured beta-endorphin levels.","limitations":"Cross-sectional study. CSF levels may not reflect activity at pain-processing sites. Normal total levels do not rule out local deficiencies or functional problems with the opioid system."},{"rthcId":"RPEP-00216","title":"Endogenous opioid peptides and blood pressure regulation during controlled, stepwise hemorrhagic hypotension.","authors":"van den Berg, M H; van Giersbergen, P L; Cox-van Put, J; de Jong, W","year":1991,"journal":"Circulatory shock, 35(2), 102-8","doi":null,"pmid":"1723353","tags":["opioid-peptides","cardiovascular","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Central and peripheral naloxone increased bleeding volumes before pressure dropped. Brain antibodies against beta-endorphin, alpha-endorphin, and dynorphin A also improved hemorrhage tolerance.","whyItMatters":"This reveals that the body's opioid peptides actually make hemorrhagic shock worse. Blocking them could improve survival during severe blood loss, a finding relevant to trauma and emergency medicine.","specificNumbers":"","methodology":"Anesthetized rats underwent controlled stepwise hemorrhage. Naloxone, peripheral naloxone methobromide, or opioid peptide antibodies were administered centrally. Bleeding volumes at each pressure step were measured.","limitations":"Animal study in anesthetized rats. Anesthesia and controlled hemorrhage differ from real trauma. Antibody specificity may not be perfect. Clinical translation is not straightforward."},{"rthcId":"RPEP-00217","title":"Effects of dynorphin A(1-13) and of fragments of beta-endorphin on blood pressure and heart rate of anesthetized rats.","authors":"van Giersbergen, P L; de Lang, H; de Jong, W","year":1991,"journal":"Canadian journal of physiology and pharmacology, 69(3), 327-33","doi":null,"pmid":"1676337","tags":["opioid-peptides","cardiovascular","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Full beta-endorphin caused naltrexone-reversible hypotension and bradycardia. N-terminally modified fragments were inactive. Beta-endorphin(1-27) induced both hypertensive and hypotensive responses.","whyItMatters":"This shows that the full opioid-active portion of beta-endorphin is needed for its cardiovascular effects. Understanding which parts of the molecule are essential helps in designing peptide-based drugs.","specificNumbers":"","methodology":"Anesthetized rats received intracerebroventricular injections of beta-endorphin, its fragments, gamma-endorphin, alpha-endorphin fragments, and dynorphin A(1-13) at various doses. Blood pressure and heart rate were continuously recorded.","limitations":"Animal study in anesthetized rats. Anesthesia affects cardiovascular reflexes. Brain injections do not reflect normal physiology. Only acute effects studied."},{"rthcId":"RPEP-00218","title":"Industry perspective on the validation of column-based separation processes for the purification of proteins. Parenteral Drug Association.","authors":"","year":1992,"journal":"Journal of parenteral science and technology : a publication of the Parenteral Drug Association, 46(3), 87-97","doi":null,"pmid":"1522447","tags":["peptide-design","peptide-safety","regulatory"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Column purification validation requires qualification of raw materials, equipment, and process, ideally designed in from the start. Combined with quality control, this ensures batch-to-batch consistency.","whyItMatters":"Peptide drugs must be extremely pure. This review provides the framework that pharmaceutical manufacturers use to ensure the purification step consistently removes dangerous impurities.","specificNumbers":"","methodology":"Industry perspective review from the Parenteral Drug Association covering validation principles and practices for column-based protein/peptide purification.","limitations":"Industry perspective from 1992. Regulatory requirements have evolved significantly. Some specific techniques may be outdated, though the principles remain."},{"rthcId":"RPEP-00219","title":"Wegrowski 1992 Stimulation Of Sulfated Glycosaminoglyca","authors":"","year":1992,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00220","title":"Properties and functions of human placental opioid system.","authors":"Ahmed, M S; Cemerikic, B; Agbas, A","year":1992,"journal":"Life sciences, 50(2), 83-97","doi":null,"pmid":"1309934","tags":["opioid-peptides","fertility","receptor-signaling"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Human placenta contains exclusively kappa opioid receptors (MW ~63,000). They regulate acetylcholine and hCG/placental lactogen release. Receptor numbers correlate with birth weight at term.","whyItMatters":"The placenta has its own opioid system that influences pregnancy hormones and fetal growth. This has implications for how opioid drugs during pregnancy might affect the baby.","specificNumbers":"","methodology":"Review of studies on human placental villus tissue including receptor binding, purification, functional assays, and correlations with pregnancy outcomes.","limitations":"Review based on in vitro placental tissue studies. Functional significance in vivo may differ. Only kappa receptors were found, but detection methods from 1992 may have missed very low levels of other types."},{"rthcId":"RPEP-00221","title":"Hypothalamic corticotropin-releasing hormone and opioid peptide neurons: functional changes after adrenalectomy and/or castration.","authors":"Almeida, O F; Hassan, A H; Harbuz, M S; Linton, E A; Lightman, S L","year":1992,"journal":"Brain research, 571(2), 189-98","doi":null,"pmid":"1351778","tags":["opioid-peptides","hormone-optimization","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Adrenalectomy and castration independently and interactively regulated hypothalamic CRH mRNA, CRH peptide, opioid peptide content, and CRF-stimulated opioid release.","whyItMatters":"This shows that testosterone and cortisol together calibrate the brain's opioid peptide system. Disruptions in either hormone could change pain sensitivity, stress responses, and mood.","specificNumbers":"","methodology":"Male rats underwent sham surgery, adrenalectomy, castration, or both. Short-term and long-term effects on hypothalamic CRH and opioid peptides were measured, including in vitro release studies.","limitations":"Animal study using surgical hormone removal, which is more extreme than natural hormonal changes. Only male rats studied. In vitro release may not fully reflect in vivo dynamics."},{"rthcId":"RPEP-00222","title":"Influence of opioids on CSF vasopressin concentration in newborn pigs.","authors":"Armstead, W M; Crofton, J T; Share, L; Mirro, R; Zuckerman, S L; Leffler, C W","year":1992,"journal":"The American journal of physiology, 262(3 Pt 2), H862-7","doi":null,"pmid":"1348399","tags":["opioid-peptides","cardiovascular","neuropeptides"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Topical dynorphin(1-13) dilated pial arteries during normotension but constricted them during hypotension. It increased CSF vasopressin concentration in both states.","whyItMatters":"Dynorphin's ability to cause opposite blood vessel responses depending on blood pressure status makes it a sophisticated regulator. This has implications for understanding how the newborn brain protects itself during blood pressure emergencies.","specificNumbers":"","methodology":"Newborn pigs with closed cranial windows received topical dynorphin application to the brain surface. Pial arteriolar diameter and CSF vasopressin were measured during normotension and hemorrhagic hypotension.","limitations":"Animal study in newborn pigs with topical drug application. The cranial window model alters normal conditions. May not represent deeper brain tissue responses."},{"rthcId":"RPEP-00223","title":"Plasma endogenous opioid levels in acute myocardial infarction patients, with and without pain.","authors":"Bernardi, P; Fontana, F; Pich, E M; Spampinato, S; Canossa, M","year":1992,"journal":"European heart journal, 13(8), 1074-9","doi":null,"pmid":"1354615","tags":["opioid-peptides","cardiovascular","pain"],"studyType":"cross-sectional","evidenceStrength":"moderate","keyFinding":"Transient plasma beta-endorphin elevation in painful AMI (Group II, n=16) that normalized when pain ceased. No changes in painless AMI (Group I, n=12). Met-enkephalin and dynorphin unchanged in both.","whyItMatters":"This study separates the body's opioid response to pain from the heart damage itself. It also raises the question of whether the lack of a beta-endorphin response contributes to the phenomenon of silent heart attacks.","specificNumbers":"","methodology":"Blood samples from AMI patients collected on admission (1-3 hours post-MI), at 7, 12, 24 hours, and at 2, 3, 4 days. Beta-endorphin, met-enkephalin, and dynorphin measured by immunoassay.","limitations":"Observational study with relatively small groups. Blood opioid levels may not reflect brain or cardiac tissue levels. Cannot determine if opioid differences cause or result from painless MI."},{"rthcId":"RPEP-00224","title":"Effects of delta sleep-inducing peptide on sleep of chronic insomniac patients. A double-blind study.","authors":"Bes, F; Hofman, W; Schuur, J; Van Boxtel, C","year":1992,"journal":"Neuropsychobiology, 26(4), 193-7","doi":null,"pmid":"1299794","tags":["neuropeptides"],"studyType":"rct","evidenceStrength":"moderate","keyFinding":"In this double-blind trial, delta sleep-inducing peptide (DSIP) showed some objective sleep improvements in chronic insomniacs — higher sleep efficiency and shorter time to fall asleep compared to placebo. One subjective tiredness measure also improved.\n\nHowever, the researchers concluded these effects were weak and potentially confounded by changes in the placebo group. Other measures including subjective sleep quality showed no improvement. The authors' overall conclusion was negative: short-term DSIP treatment is unlikely to provide major therapeutic benefit for chronic insomnia.","whyItMatters":"DSIP was one of the earliest peptides investigated as a potential sleep aid, generating significant excitement when it was first identified in the 1970s. This was one of the few properly controlled human trials testing whether DSIP actually improves sleep. The largely negative result was important for the field — it tempered expectations about DSIP as a therapeutic peptide and highlighted the gap between a peptide's name/theoretical function and its actual clinical utility.","specificNumbers":"n=16 patients · Double-blind, parallel groups · 25 nmol/kg body weight DSIP IV · 3 treatment nights · Higher sleep efficiency and shorter sleep latency vs. placebo (but weak effects) · No subjective sleep quality improvement","methodology":"Double-blind, matched-pairs, parallel-groups design. 16 chronic insomnia patients spent 5 consecutive nights in a sleep lab. Night 1 was adaptation, night 2 was baseline. Before nights 3-5, half received IV DSIP (25 nmol/kg) and half received glucose placebo. Polysomnography measured objective sleep architecture, and subjective sleep quality and tiredness were also assessed.","limitations":"Very small sample size (n=16, only 8 per group). Only 3 treatment nights — too short to assess sustained effects. IV administration is impractical for real-world insomnia treatment. The statistically significant findings were weak and potentially driven by placebo group changes rather than true DSIP effects. Published in 1992 with older statistical methods."},{"rthcId":"RPEP-00225","title":"Central effects of tumor necrosis factor alpha and interleukin-1 alpha on nociceptive thresholds and spontaneous locomotor activity.","authors":"Bianchi, M; Sacerdote, P; Ricciardi-Castagnoli, P; Mantegazza, P; Panerai, A E","year":1992,"journal":"Neuroscience letters, 148(1-2), 76-80","doi":null,"pmid":"1300507","tags":["neuropeptides","pain","inflammation","immune-function"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Central TNF-alpha and IL-1-alpha both increased nociceptive thresholds. TNF-alpha decreased locomotion. Naloxone partially reversed TNF-alpha's analgesic effect.","whyItMatters":"This links the immune system directly to brain pain control. During infection or inflammation, cytokines in the brain may change pain sensitivity, which could explain pain changes during illness.","specificNumbers":"","methodology":"Rats received intracerebroventricular injections of TNF-alpha or IL-1-alpha. Pain thresholds were tested using the hot-plate method. Locomotor activity was recorded. Naloxone was used to test opioid involvement.","limitations":"Animal study with direct brain injection. Doses may not reflect natural cytokine levels during inflammation. Acute effects only studied."},{"rthcId":"RPEP-00226","title":"Selectivity and potency of opioid peptides in regulating human chorionic gonadotropin release from term trophoblast tissue.","authors":"Cemerikic, B; Schabbing, R; Ahmed, M S","year":1992,"journal":"Peptides, 13(5), 897-903","doi":null,"pmid":"1362265","tags":["opioid-peptides","fertility","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Order of potency for hCG release: kappa >>> mu > delta. All three produced bell-shaped dose-response curves. Kappa dominance confirmed.","whyItMatters":"This confirms the placenta uses kappa opioid signaling to regulate a critical pregnancy hormone. Opioid drugs during pregnancy could directly alter hCG levels, which is essential for maintaining pregnancy.","specificNumbers":"","methodology":"Term human trophoblast tissue was cultured in vitro with opioid agonists selective for kappa (dynorphin 1-13), mu (DAMGO), and delta (DPDPE) receptors. hCG release was measured.","limitations":"In vitro study using isolated placental tissue. May not reflect the complexity of intact placental function. Only hCG measured."},{"rthcId":"RPEP-00227","title":"Vitamin D3 and calcium to prevent hip fractures in elderly women.","authors":"Chapuy, M C; Arlot, M E; Duboeuf, F; Brun, J; Crouzet, B; Arnaud, S; Delmas, P D; Meunier, P J","year":1992,"journal":"The New England journal of medicine, 327(23), 1637-42","doi":null,"pmid":"1331788","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00228","title":"Delta and kappa opiate receptors in primary astroglial cultures. Part II: Receptor sets in cultures from various brain regions and interactions with beta-receptor activated cyclic AMP.","authors":"Eriksson, P S; Hansson, E; Rönnbäck, L","year":1992,"journal":"Neurochemical research, 17(6), 545-51","doi":null,"pmid":"1318509","tags":["opioid-peptides","receptor-signaling","neuropeptides"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Delta and kappa opioid receptors were co-localized on astroglia from cortex, striatum, and brainstem. Both inhibited adenylate cyclase and modulated beta-receptor-stimulated cAMP.","whyItMatters":"Brain support cells (astroglia) outnumber neurons. Finding functional opioid receptors on them means the opioid system affects brain function more broadly than just through neurons.","specificNumbers":"","methodology":"Primary astroglial cultures from neonatal rat cortex, striatum, and brainstem were treated with receptor-selective opioid ligands. cAMP accumulation was measured.","limitations":"In vitro cell culture study using neonatal cells. Cultured astroglia may not behave the same as mature cells in the intact brain. Mu receptors were not detected."},{"rthcId":"RPEP-00229","title":"Effects of beta-endorphin on spontaneous uterine contractions. Prostaglandins production and 45Ca2+ uptake in uterine strips from ovariectomized rats.","authors":"Faletti, A; Bassi, D; Gimeno, A L; Gimeno, M A","year":1992,"journal":"Prostaglandins, leukotrienes, and essential fatty acids, 47(1), 29-33","doi":null,"pmid":"1359570","tags":["opioid-peptides","fertility","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Beta-endorphin (10^-6 M) reduced uterine contractions, prostaglandin synthesis, and calcium uptake. Naloxone did not block it. Other opioids were inactive.","whyItMatters":"Beta-endorphin can relax the uterus through a non-opioid pathway. This is relevant to understanding uterine physiology during labor and why opioid pain drugs may have unexpected effects on uterine contractions.","specificNumbers":"","methodology":"Uterine strips from ovariectomized rats were suspended in organ baths. Isometric tension was recorded during treatment with opioid peptides. Prostaglandin and calcium uptake were also measured.","limitations":"In vitro study using uterine strips from ovariectomized rats. Conditions differ from intact pregnancy. Non-opioid mechanism was not identified."},{"rthcId":"RPEP-00230","title":"Interaction of opioid peptide-containing terminals with dopaminergic perikarya in the rat hypothalamus.","authors":"Fitzsimmons, M D; Olschowka, J A; Wiegand, S J; Hoffman, G E","year":1992,"journal":"Brain research, 581(1), 10-8","doi":null,"pmid":"1498660","tags":["opioid-peptides","hormone-optimization","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Electron microscopy demonstrated direct contact between opioid peptide-containing terminals and tyrosine hydroxylase-positive (dopaminergic) cell bodies in the rat hypothalamus.","whyItMatters":"This provides the physical wiring diagram for how the brain's opioid system controls dopamine and prolactin. This circuit is relevant to fertility, lactation, and opioid drug side effects.","specificNumbers":"","methodology":"Electron microscopic immunocytochemistry with antibodies against opioid peptides and tyrosine hydroxylase (a dopamine neuron marker) in rat hypothalamus.","limitations":"Anatomical study showing structure but not function. Electron microscopy captures snapshots, not dynamic interactions. Rat anatomy may differ from human."},{"rthcId":"RPEP-00231","title":"Kappa opioid agonists inhibit transmitter release from guinea pig hippocampal mossy fiber synaptosomes.","authors":"Gannon, R L; Terrian, D M","year":1992,"journal":"Neurochemical research, 17(8), 741-7","doi":null,"pmid":"1353613","tags":["opioid-peptides","neuroprotection","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Kappa agonists U-62,066E and ethylketocyclazocine inhibited potassium-evoked glutamate and dynorphin B release from mossy fiber synaptosomes. Mu (DAGO) and delta (DPDPE) agonists were inactive.","whyItMatters":"Kappa receptors on hippocampal mossy fibers can dial down excitatory signaling. This natural brake system could protect the brain from seizures and excitotoxic damage.","specificNumbers":"","methodology":"Guinea pig hippocampal mossy fiber synaptosomes were isolated. Potassium-evoked release of L-glutamate and dynorphin B was measured in the presence of opioid receptor subtype-selective agonists.","limitations":"In vitro study using isolated nerve terminals. May not reflect the complex regulation in intact hippocampal circuits. Guinea pig results may differ from humans."},{"rthcId":"RPEP-00232","title":"Detection of prodynorphin end products in lizard, turtle, and alligator brain extracts.","authors":"Goldsmith, A M; Sei, C A; Lance, V; Dores, R M","year":1992,"journal":"Peptides, 13(3), 435-40","doi":null,"pmid":"1355904","tags":["opioid-peptides","neuropeptides"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"All four prodynorphin end products detected in turtle, lizard, and alligator brains by radioimmunoassay and chromatography.","whyItMatters":"Finding dynorphin peptides in all major reptile lineages establishes that the prodynorphin system is ancient and was present before reptiles and mammals diverged.","specificNumbers":"","methodology":"Brain acid extracts from Pseudemys scripta (turtle), Anolis carolinensis (lizard), and Alligator mississippiensis were fractionated by gel filtration and analyzed by radioimmunoassay.","limitations":"Heterologous mammalian antibodies used, which may not perfectly detect reptilian peptide variants. Only whole brain extracts analyzed, not regional distribution."},{"rthcId":"RPEP-00233","title":"Resistance to host antimicrobial peptides is necessary for Salmonella virulence.","authors":"Groisman, E A; Parra-Lopez, C; Salcedo, M; Lipps, C J; Heffron, F","year":1992,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 89(24), 11939-43","doi":null,"pmid":"1465423","tags":["antimicrobial-peptides","infection","immune-function"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Salmonella genes required for antimicrobial peptide resistance were also required for macrophage survival and mouse virulence. Mutants were sensitive to both insect and mammalian peptides.","whyItMatters":"This proves that the body's antimicrobial peptides are a critical defense against Salmonella. It also shows that antimicrobial peptide resistance is essential for bacterial virulence, making it a potential drug target.","specificNumbers":"","methodology":"20,000 MudJ transposon insertion mutants of virulent S. typhimurium were screened for sensitivity to the antimicrobial peptide melittin. Susceptible mutants were tested against other peptides, in macrophage survival assays, and in mouse infection models.","limitations":"Mouse model using a specific Salmonella strain. Resistance mechanisms may differ across bacterial species. Some genes identified may have additional functions beyond peptide resistance."},{"rthcId":"RPEP-00234","title":"Beta-endorphin processing and cellular origins in rat spinal cord.","authors":"Gutstein, Howard B; Bronstein, David M; Akil, Huda","year":1992,"journal":"Pain, 51(2), 241-247","doi":"10.1016/0304-3959(92)90265-D","pmid":"1336592","tags":["opioid-peptides","pain","neuropeptides"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Beta-endorphin and POMC processing products were found in rat spinal cord cells, suggesting local production beyond supraspinal sources.","whyItMatters":"If the spinal cord makes its own beta-endorphin, it has an independent pain-control system. This could be targeted for pain treatment without affecting the brain.","specificNumbers":"","methodology":"Immunohistochemistry and molecular techniques were used to detect beta-endorphin forms and POMC products in rat spinal cord tissue sections and extracts.","limitations":"Animal study in rats. Distinguishing local production from brain-derived supply is technically challenging. Antibody cross-reactivity possible."},{"rthcId":"RPEP-00235","title":"Thymic involution in aging. Prospects for correction.","authors":"Hadden, J W; Malec, P H; Coto, J; Hadden, E M","year":1992,"journal":"Annals of the New York Academy of Sciences, 673, 231-9","doi":null,"pmid":"1485720","tags":["thymosin-alpha-1","immune-function","anti-aging"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Thymic hormones (thymosin alpha-1, thymulin, thymopoietin) decline with age alongside thymic involution, and their supplementation shows potential for partially restoring age-related immune deficits.","whyItMatters":"Age-related immune decline is a major driver of illness in older adults. Understanding and potentially reversing thymic involution through peptide supplementation could improve immune health in aging populations.","specificNumbers":"","methodology":"Literature review synthesizing evidence on thymic involution, thymic hormone levels across age, and therapeutic attempts to restore immune function through thymic hormone supplementation.","limitations":"As a review, no new experimental data is presented. Most evidence at the time came from animal models, with limited human clinical data on thymic hormone replacement."},{"rthcId":"RPEP-00236","title":"Dynorphin, a preferential ligand for kappa-opioid receptors, is present in nerve fibers and immune cells within inflamed tissue of the rat.","authors":"Hassan, A H; Pzewłocki, R; Herz, A; Stein, C","year":1992,"journal":"Neuroscience letters, 140(1), 85-8","doi":null,"pmid":"1357608","tags":["opioid-peptides","pain","inflammation","immune-function"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Dynorphin immunoreactivity detected in both inflammatory cells and cutaneous sensory nerve fibers in Freund's adjuvant-inflamed rat paw tissue.","whyItMatters":"This shows the body has a local pain-relief system at inflammation sites. Immune cells produce dynorphin right where it is needed, which could be enhanced for better pain treatment.","specificNumbers":"","methodology":"Immunohistochemistry for dynorphin and calcitonin gene-related peptide (CGRP, a sensory nerve marker) on tissue sections from inflamed and normal rat hindpaws.","limitations":"Animal study in rats with a chemical inflammation model. Immunohistochemistry shows presence but not release or activity. Cannot quantify how much dynorphin the immune cells produce."},{"rthcId":"RPEP-00237","title":"Hippocampal opioid peptides and seizures.","authors":"Hong, J S","year":1992,"journal":"Epilepsy research. Supplement, 7, 187-95","doi":null,"pmid":"1361330","tags":["opioid-peptides","neuroprotection","neuropeptides"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Both seizure types caused initial opioid release. Long-term: enkephalin biosynthesis increased, dynorphin biosynthesis drastically decreased. These peptides are in distinct hippocampal pathways.","whyItMatters":"The opposite long-term changes in enkephalin vs. dynorphin could affect whether the brain becomes more or less susceptible to future seizures. This has implications for epilepsy treatment.","specificNumbers":"","methodology":"Molecular biology approach measuring mRNA levels and peptide content for prodynorphin and proenkephalin in rat hippocampus after electroconvulsive shocks and amygdala kindling.","limitations":"Animal study using experimental seizure models. The electroconvulsive and kindling models may not perfectly represent human epilepsy. Only hippocampus studied."},{"rthcId":"RPEP-00238","title":"Endorphins do not affect behavioral stress responses in mice.","authors":"Katoh, A; Nabeshima, T; Ukai, R; Kameyama, T","year":1992,"journal":"Peptides, 13(4), 737-9","doi":null,"pmid":"1437715","tags":["opioid-peptides","anxiety-mood"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"ICV alpha-endorphin (2.5-10 nmol), beta-endorphin (0.38-1.5 nmol), and gamma-endorphin (2.5-10 nmol) did not affect conditioned suppression or forced swim immobility in mice.","whyItMatters":"This negative result is important because it challenges the popular assumption that endorphins directly control stress and mood behaviors. The reality may be more complex.","specificNumbers":"","methodology":"Mice received intracerebroventricular injections of endorphin peptides. Behavior was assessed in conditioned suppression of motility and forced swimming tests.","limitations":"Negative results may reflect dose range, timing, or species-specific effects. Mice may use different stress-coping mechanisms than rats or humans. Only acute effects tested."},{"rthcId":"RPEP-00239","title":"Vasoactive intestinal polypeptide induces neurogenic contraction of guinea-pig ileum. Involvement of acetylcholine and substance P.","authors":"Katsoulis, S; Schmidt, W E; Clemens, A; Schwörer, H; Creutzfeldt, W","year":1992,"journal":"Regulatory peptides, 38(2), 155-64","doi":null,"pmid":"1374193","tags":["neuropeptides","gut-healing","opioid-peptides"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"VIP (20 nM-1 microM) induced neurogenic gut contractions via acetylcholine and substance P. Dynorphin (100 nM) and somatostatin (60 nM) abolished these contractions.","whyItMatters":"This shows how multiple neuropeptides interact in the gut nervous system. Dynorphin's ability to shut down VIP-driven contractions explains part of how opioids cause constipation.","specificNumbers":"","methodology":"Guinea pig ileal longitudinal muscle strips in organ baths. VIP-induced contractions measured with and without nerve blockers, receptor antagonists, dynorphin, and somatostatin.","limitations":"In vitro study in guinea pig gut. Isolated tissue may not reflect intact gut physiology. Species differences in gut pharmacology exist."},{"rthcId":"RPEP-00240","title":"Dynorphin-(1-13): antinociceptive action and its effects on morphine analgesia and acute tolerance.","authors":"Kishioka, S; Morita, N; Kitabata, Y; Yamanishi, T; Miyamoto, Y; Ozaki, M; Yamamoto, H","year":1992,"journal":"Japanese journal of pharmacology, 60(3), 197-207","doi":null,"pmid":"1362787","tags":["opioid-peptides","pain","addiction"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Dynorphin(1-13) ICV produced dose-dependent antinociception. It prevented acute morphine tolerance development. Potency order: beta-endorphin > morphine > dynorphin >> met-enkephalin.","whyItMatters":"If dynorphin prevents morphine tolerance, it could be used alongside morphine to maintain pain relief in chronic pain patients without needing increasing doses.","specificNumbers":"","methodology":"Male rats received ICV dynorphin(1-13) at various doses. Pain was tested using hind paw pressure and acetic acid writhing. Morphine tolerance was assessed by repeated dosing with and without prior dynorphin.","limitations":"Animal study with brain injection. High doses needed for pain relief raise questions about practicality. Acute tolerance prevention may not translate to chronic use."},{"rthcId":"RPEP-00241","title":"Age-related changes in opioid peptide concentrations in brain and pituitary of spontaneously hypertensive rats. Effect of antihypertensive drugs and comparison with deoxycorticosterone acetate and salt hypertension.","authors":"Li, S J; Wong, S C; Hong, J S; Ingenito, A J","year":1992,"journal":"Pharmacology, 44(5), 245-56","doi":null,"pmid":"1352404","tags":["opioid-peptides","cardiovascular","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"SHR rats had distinct age-dependent opioid peptide profiles in brain regions linked to blood pressure control. Antihypertensive drugs partially normalized these changes.","whyItMatters":"This connects brain opioid peptide changes to hypertension development. If opioid abnormalities contribute to high blood pressure, they could be targets for new treatments.","specificNumbers":"","methodology":"Opioid peptide concentrations measured by radioimmunoassay in brain regions and pituitary of SHR, WKY, and SD rats at ages 4, 8, 12, 16, and 20 weeks. Effects of antihypertensive drugs and DOCA-salt hypertension also examined.","limitations":"Animal study in a genetic hypertension model. SHR rats are highly inbred and may not represent human essential hypertension. Correlation does not prove causation."},{"rthcId":"RPEP-00242","title":"Characterization of opioid receptors mediating stimulation of adenylate cyclase activity in rat olfactory bulb.","authors":"Olianas, M C; Onali, P","year":1992,"journal":"Molecular pharmacology, 42(1), 109-15","doi":null,"pmid":"1321951","tags":["opioid-peptides","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Delta opioid receptors primarily mediate adenylate cyclase stimulation in olfactory bulb. Deltorphin I EC50 = 6.7 nM. Mu receptors contribute. Kappa receptors inactive.","whyItMatters":"Identifying the specific receptor (delta) responsible for unusual stimulatory opioid signaling helps explain how the same receptor family can produce opposite effects in different brain regions.","specificNumbers":"","methodology":"Rat olfactory bulb homogenates treated with selective opioid agonists and antagonists. Adenylate cyclase activity measured. Concentration-response curves and antagonist profiles determined.","limitations":"In vitro tissue homogenate study. Cannot identify the specific cell types responsible. The G-protein coupling mechanism for stimulation was not fully characterized."},{"rthcId":"RPEP-00243","title":"Inhibition of oestradiol-induced DNA synthesis by opioid peptides in the rat uterus.","authors":"Ordög, T; Vértes, Z; Vértes, M","year":1992,"journal":"Life sciences, 51(15), 1187-96","doi":null,"pmid":"1528088","tags":["opioid-peptides","fertility","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"DMEPA (enkephalin analog) inhibited estradiol-induced uterine DNA synthesis by ~50% when given 1-2 hours before measurement. Naloxone partially reversed the effect.","whyItMatters":"This shows opioid peptides can suppress estrogen-driven tissue growth. This could be relevant to conditions like endometriosis and uterine cancer where estrogen-driven growth is a problem.","specificNumbers":"","methodology":"Ovariectomized rats received estradiol injection followed by DMEPA at various time points. Uterine DNA synthesis was measured by in vitro thymidine incorporation 24 hours after estradiol.","limitations":"Animal study in ovariectomized rats, which is an artificial hormonal state. Only one enkephalin analog tested. The mechanism of growth inhibition was not fully characterized."},{"rthcId":"RPEP-00244","title":"Opioid peptide drug development: transport of opioid chimeric peptides through the blood-brain barrier.","authors":"Pardridge, W M","year":1992,"journal":"NIDA research monograph, 120, 153-68","doi":null,"pmid":"1501684","tags":["opioid-peptides","peptide-delivery","bioavailability","addiction"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Chimeric peptides coupling opioid peptides to BBB transport vectors allow brain delivery of enkephalin and dynorphin analogs in vivo. The strategy has advantages for addiction drug development.","whyItMatters":"Getting peptide drugs into the brain is one of the biggest challenges in neuroscience. Chimeric peptides solve this problem for opioid peptides, enabling new pain and addiction treatments.","specificNumbers":"","methodology":"Review of research on chimeric peptide drug delivery across the blood-brain barrier, including vector development and in vivo demonstration of opioid peptide brain transport.","limitations":"Review from 1992. The chimeric peptide approach was early-stage. Practical challenges include stability, immunogenicity, and manufacturing scale-up."},{"rthcId":"RPEP-00245","title":"Differential effects of opioid receptor agonists on nociception and cAMP level in the spinal cord of monoarthritic rats.","authors":"Przewłocka, B; Dziedzicka, M; Lasoń, W; Przewłocki, R","year":1992,"journal":"Life sciences, 50(1), 45-54","doi":null,"pmid":"1345879","tags":["opioid-peptides","pain","inflammation","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Intrathecal mu and delta agonists produced enhanced antinociception in monoarthritic rats with greater cAMP inhibition. Kappa agonists showed no enhancement.","whyItMatters":"Chronic inflammation amplifies the spinal cord's response to certain opioids. This means lower doses might work better for inflammatory pain, potentially reducing side effects.","specificNumbers":"","methodology":"Monoarthritic rats received intrathecal opioid agonists. Pain was assessed by tail-flick test. Spinal cord cAMP levels were measured to assess receptor-linked molecular changes.","limitations":"Animal study using a chemical arthritis model. Rat spinal pharmacology may differ from human. Only one inflammatory model used."},{"rthcId":"RPEP-00246","title":"Gene expression and localization of opioid peptides in immune cells of inflamed tissue: functional role in antinociception.","authors":"Przewłocki, R; Hassan, A H; Lason, W; Epplen, C; Herz, A; Stein, C","year":1992,"journal":"Neuroscience, 48(2), 491-500","doi":null,"pmid":"1603330","tags":["opioid-peptides","pain","inflammation","immune-function"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"All three opioid precursor mRNAs detected in inflamed tissue. Opioid peptides localized to immune cells. Local opioid blockade increased pain, proving functional significance.","whyItMatters":"This proves the immune system produces painkillers at injury sites. It opens the door to treatments that enhance this natural local pain relief without systemic opioid side effects.","specificNumbers":"","methodology":"Freund's adjuvant-inflamed rat hindpaw tissue was analyzed for opioid mRNA (in situ hybridization), opioid peptide immunoreactivity (immunohistochemistry), and functional pain testing with local naloxone.","limitations":"Animal study in rats with a chemical inflammation model. The amount of opioid peptides produced by immune cells may vary with inflammation type and severity."},{"rthcId":"RPEP-00247","title":"Potentiation of brain natriuretic peptides by SQ 28,603, an inhibitor of neutral endopeptidase 3.4.24.11, in monkeys and rats.","authors":"Seymour, A A; Asaad, M M; Abboa-Offei, B E; Rovnyak, P L; Fennell, S; Rogers, W L","year":1992,"journal":"The Journal of pharmacology and experimental therapeutics, 262(1), 60-70","doi":null,"pmid":"1385630","tags":["natriuretic-peptides","cardiovascular"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"NEP inhibitor SQ 28,603 markedly potentiated BNP-32 responses in SHR and monkeys. BNP was more resistant to NEP degradation than ANP. Cyclic GMP responses also potentiated.","whyItMatters":"This research laid groundwork for drugs like sacubitril (Entresto) that protect natriuretic peptides from degradation. These drugs are now standard heart failure treatment.","specificNumbers":"","methodology":"Conscious spontaneously hypertensive rats and cynomolgus monkeys received BNP or ANP with or without NEP inhibitor SQ 28,603. Blood pressure, natriuresis, and cyclic GMP were measured.","limitations":"Animal study in two species. Doses and routes differ from clinical use. SHR model is one type of hypertension."},{"rthcId":"RPEP-00248","title":"Serum procollagen peptides and collagen type VI for the assessment of activity and degree of hepatic fibrosis in schistosomiasis and alcoholic liver disease.","authors":"Shahin, M; Schuppan, D; Waldherr, R; Risteli, J; Risteli, L; Savolainen, E R; Oesterling, C; Abdel Rahman, H M; el Sahly, A M; Abdel Razek, S M","year":1992,"journal":"Hepatology (Baltimore, Md.), 15(4), 637-44","doi":null,"pmid":"1551641","tags":["peptide-biomarkers","liver-fibrosis"],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"Blood levels of procollagen peptides — particularly procollagen type III N-propeptide (PIIINP) — tracked with the severity of liver scarring in both schistosomiasis and alcoholic liver disease. PIIINP was significantly elevated in all schistosomiasis patient groups compared to healthy controls (p<0.01), and patients with worse scarring on biopsy had higher PIIINP levels (p<0.05). In alcoholic patients, PIIINP was even higher and rose with disease severity.\n\nInterestingly, procollagen type I C-propeptide was only elevated during early infection and decreased as disease progressed, suggesting it reflects early-stage collagen production while PIIINP better captures ongoing active fibrosis. Different collagen markers appeared to track different aspects of the scarring process — synthesis versus degradation.","whyItMatters":"Liver fibrosis progresses silently and conventional liver tests don't reveal how active the scarring process is. Liver biopsy is invasive and only captures a small sample. Blood-based peptide biomarkers like procollagen propeptides could offer a non-invasive way to monitor fibrosis activity in real time — critical for the hundreds of millions of people worldwide with chronic liver disease from various causes.","specificNumbers":"n=100 (15 controls + 69 schistosomiasis + 16 alcoholic cirrhosis) · PIIINP elevated p<0.01 · higher histological grade = higher PIIINP p<0.05 · 30 liver biopsies","methodology":"Cross-sectional study measuring serum concentrations of four collagen-related peptide markers (procollagen type III N-propeptide, procollagen type I C-propeptide, procollagen type IV C-propeptide, and collagen type VI) in healthy controls, three stages of schistosomiasis infection, and alcoholic cirrhosis patients. Correlated with liver biopsy histopathology and collagen histochemistry in 30 schistosomal patients.","limitations":"Relatively small sample sizes across groups, especially controls (n=15) and alcoholic cirrhosis (n=16). Cross-sectional design cannot track how biomarker levels change over time in individual patients. The abstract was truncated, so some results regarding collagen type VI and type IV markers are not fully reported. The study is from 1992 and newer fibrosis markers have since been developed."},{"rthcId":"RPEP-00249","title":"Tachykinin systems in the spinal cord and basal ganglia: influence of neonatal capsaicin treatment or dopaminergic intervention on levels of peptides, substance P-encoding mRNAs, and substance P receptor mRNA.","authors":"Sivam, S P; Krause, J E","year":1992,"journal":"Journal of neurochemistry, 59(6), 2278-84","doi":null,"pmid":"1279124","tags":["neuropeptides","pain","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Capsaicin reduced spinal SP and NKA without changing NK1 receptor mRNA. Haloperidol increased basal ganglia SP mRNA without changing NK1 receptor mRNA.","whyItMatters":"Understanding that the peptide and its receptor are independently controlled means we cannot assume that changing one automatically changes the other. This is important for designing drugs that target the substance P system.","specificNumbers":"","methodology":"Neonatal rats received capsaicin to destroy sensory neurons. Adult rats received haloperidol for dopaminergic disruption. SP, NKA, SP mRNA, and NK1 receptor mRNA were measured.","limitations":"Animal study in rats with pharmacological and chemical manipulations. Results may not apply to all conditions or species. Only mRNA measured for the receptor."},{"rthcId":"RPEP-00250","title":"Reciprocal effects between opioid peptides and human polymorphonuclear leukocytes--II. Enhancement of phorbol myristate acetate-induced respiratory burst in human polymorphonuclear leukocyte by opioid peptides previously exposed to activated oxygen species.","authors":"Slaoui-Hasnaoui, A; Guerin, M C; Le Doucen, C; Loubatiere, J; Torreilles, J","year":1992,"journal":"Biochemical pharmacology, 43(3), 503-6","doi":null,"pmid":"1540208","tags":["opioid-peptides","immune-function","inflammation"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Native opioid peptides did not affect PMN respiratory burst. Opioid peptides modified by activated oxygen species enhanced PMA-stimulated respiratory burst.","whyItMatters":"At inflammation sites, opioid peptides get modified by reactive oxygen and turn into immune activators. This means opioid peptides have different functions depending on the chemical environment.","specificNumbers":"","methodology":"Human polymorphonuclear leukocytes (PMNs) were stimulated with PMA. Opioid peptides (native and AOS-modified) were tested for effects on respiratory burst using chemiluminescence or other oxidative assays.","limitations":"In vitro study using chemically modified peptides. The specific modifications caused by AOS were not fully characterized. Clinical relevance is speculative."},{"rthcId":"RPEP-00251","title":"Characterization of the release of Met-enkephalin from isolated nerve terminals: release kinetics and cation-dependence.","authors":"Verhage, M; Ghijsen, W E; Wiegant, V M","year":1992,"journal":"Brain research, 598(1-2), 294-301","doi":null,"pmid":"1486489","tags":["opioid-peptides","receptor-signaling","neuropeptides"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Met-enkephalin release from synaptosomes was calcium-dependent with distinct kinetics. Release correlated with intraterminal free calcium but showed a different relationship than classical transmitters.","whyItMatters":"Understanding the precise mechanics of opioid peptide release could help develop drugs that enhance or reduce natural opioid release in the brain.","specificNumbers":"","methodology":"Rat forebrain synaptosomes were stimulated with KCl, veratridine, and 4-aminopyridine. Met-enkephalin was measured by a highly specific radioimmunoassay. Intraterminal calcium was monitored with fluorescent indicators.","limitations":"In vitro study using isolated nerve terminals. Synaptosomes lack the cellular context of intact neurons. Rat brain preparations mix multiple brain regions."},{"rthcId":"RPEP-00252","title":"Inactivation of Listeria monocytogenes by Lactoferricin, a Potent Antimicrobial Peptide Derived from Cow's Milk.","authors":"Wakabayashi, Hiroyuki; Bellamy, Wayne; Takase, Mitsunori; Tomita, Mamoru","year":1992,"journal":"Journal of food protection, 55(4), 238-240","doi":"10.4315/0362-028X-55.4.238","pmid":"31071777","tags":["antimicrobial-peptides","infection","bioactive-food-peptides"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Lactoferricin inhibited Listeria monocytogenes (4 serotypes) at 0.3-9 micrograms/ml. Bactericidal concentrations were slightly higher. Effectiveness comparable to clinical antibiotics.","whyItMatters":"Listeria contamination in food is a serious health threat, especially for pregnant women and immunocompromised people. A natural milk-derived peptide that kills Listeria could be used as a safe food preservative.","specificNumbers":"","methodology":"Four Listeria strains (serotypes 1b, 2, 3, 4a) were tested against lactoferricin in standard bacteriological media. Minimum inhibitory and bactericidal concentrations were determined.","limitations":"In vitro study in laboratory media. Effectiveness in actual food products may differ due to pH, salt, fats, and other food components. Only Listeria tested."},{"rthcId":"RPEP-00253","title":"Modulation of peristalsis in the guinea-pig isolated small intestine by exogenous and endogenous opioids.","authors":"Waterman, S A; Costa, M; Tonini, M","year":1992,"journal":"British journal of pharmacology, 106(4), 1004-10","doi":null,"pmid":"1356564","tags":["opioid-peptides","gut-healing","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Exogenous opioids increased peristaltic threshold volume. Naloxone decreased it, indicating endogenous opioids tonically modulate peristaltic triggering.","whyItMatters":"This provides a precise mechanical explanation for opioid-induced constipation: opioids raise the bar for how much the gut must fill before it will empty. This is directly relevant to managing this common opioid side effect.","specificNumbers":"","methodology":"Guinea pig isolated small intestine was perfused with increasing fluid volumes. Threshold volume, ejection pressure, and power were measured with and without opioid agonists and naloxone.","limitations":"In vitro study in guinea pig intestine. Isolated tissue may not fully reflect intact gut function. Only small intestine studied; effects may differ in the colon."},{"rthcId":"RPEP-00254","title":"Stimulation of sulfated glycosaminoglycan synthesis by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+.","authors":"Wegrowski, Y; Maquart, F X; Borel, J P","year":1992,"journal":"Life sciences, 51(13), 1049-56","doi":null,"pmid":"1522753","tags":["ghk-cu","wound-healing","skin-repair"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"GHK-Cu induced dose-dependent increases in both secreted and cell-associated glycosaminoglycan synthesis by normal human fibroblasts.","whyItMatters":"GAGs (like hyaluronic acid and proteoglycans) are crucial for wound healing, skin elasticity, and tissue structure. A peptide that boosts their production could accelerate healing and improve skin health.","specificNumbers":"","methodology":"Normal human fibroblasts were cultured with GHK-Cu. Cells were incubated with radiolabeled glucosamine and sulfate. GAGs were isolated and radioactivity quantified.","limitations":"In vitro study using cultured fibroblasts. Conditions differ from intact tissue. Does not show which specific GAGs are most affected. Clinical benefit not demonstrated in this study."},{"rthcId":"RPEP-00255","title":"Developmental changes of serum thymosin alpha 1 and beta 4 in male and male castrated pigs: modulation by testosterone and human chorionic gonadotropin.","authors":"Wise, T H","year":1992,"journal":"Biology of reproduction, 46(5), 892-7","doi":null,"pmid":"1591344","tags":["thymosin-alpha-1","thymosin-beta-4","hormone-optimization","fertility"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Thymosin beta 4 peaked early and declined with age. hCG challenge depressed thymosin beta 4. Testosterone modulated both thymosin beta 4 and alpha 1 levels. Castration altered the patterns.","whyItMatters":"This connects the immune system's thymic peptides directly to reproductive hormones. It helps explain why immune function changes with puberty and aging, and why castration affects immunity.","specificNumbers":"","methodology":"Male pigs (n=90) were bled at 9 time points from 1-96 weeks. hCG stimulation tests at each age. Castrated pigs received testosterone replacement. Thymosin peptides and testosterone measured by immunoassay.","limitations":"Animal study in pigs. Porcine thymic peptide regulation may differ from humans. Only male pigs studied. Immunoassay cross-reactivity possible."},{"rthcId":"RPEP-00256","title":"Intrahypothalamic neuroendocrine actions of corticotropin-releasing factor.","authors":"Almeida, O F; Hassan, A H; Holsboer, F","year":1993,"journal":"Ciba Foundation symposium, 172, 151-69; discussion 169-72","doi":null,"pmid":"8491085","tags":["neuropeptides","opioid-peptides","hormone-optimization","fertility"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"CRF fibers terminate within the hypothalamus and directly modulate the release of growth hormone, gonadotropins, and opioid peptides through local synaptic connections.","whyItMatters":"This broader understanding of CRF's effects explains how stress can simultaneously affect growth, reproduction, and pain perception through a single peptide's actions within the brain.","specificNumbers":"","methodology":"Literature review synthesizing neuroanatomical, electrophysiological, and neuroendocrine evidence on CRF's actions within the hypothalamus beyond the pituitary-adrenal axis.","limitations":"Review article synthesizing primarily animal research. Direct human evidence for intrahypothalamic CRF actions was limited at time of publication."},{"rthcId":"RPEP-00257","title":"Pancreatic polypeptide infusions reduce food intake in Prader-Willi syndrome.","authors":"Berntson, G G; Zipf, W B; O'Dorisio, T M; Hoffman, J A; Chance, R E","year":1993,"journal":"Peptides, 14(3), 497-503","doi":null,"pmid":"8332550","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00258","title":"Endogenous opioid-like substances in perinatal asphyxia and cerebral injury due to anoxia.","authors":"Cao, L; Qian, P D; Jing, L J; Liang, Q J; Zhao, Z Z","year":1993,"journal":"Chinese medical journal, 106(10), 783-7","doi":null,"pmid":"7913434","tags":["opioid-peptides","neuroprotection","neuropeptides"],"studyType":"cross-sectional","evidenceStrength":"moderate","keyFinding":"Plasma and CSF levels of all three opioid peptides were elevated in asphyxiated newborns vs. controls, with highest levels in those with cerebral injury.","whyItMatters":"Opioid peptide levels could serve as biomarkers for the severity of birth asphyxia and brain injury. They could help doctors identify which newborns are at highest risk for lasting brain damage.","specificNumbers":"","methodology":"Blood and CSF samples from 44 asphyxiated newborns and controls were analyzed for leucine-enkephalin, beta-endorphin, and dynorphin A by radioimmunoassay.","limitations":"Observational study. Cannot determine if elevated opioids are protective, harmful, or simply markers. Radioimmunoassay from 1993 was less specific than modern methods."},{"rthcId":"RPEP-00259","title":"A comparative study of growth hormone (GH) and GH-releasing hormone(1-29)-NH2 for stimulation of growth in children with GH deficiency.","authors":"Chen, R G; Shen, Y N; Yei, J; Wang, C F; Xie, D H; Wang, X H; Zhou, J D; Chen, C Y; Wu, Y L; Gunnarsson, R","year":1993,"journal":"Acta paediatrica (Oslo, Norway : 1992). Supplement, 388, 32-5; discussion 36","doi":null,"pmid":"8329830","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00260","title":"Pharmacological characterization of an opioid receptor in the ciliate Tetrahymena.","authors":"Chiesa, R; Silva, W I; Renaud, F L","year":1993,"journal":"The Journal of eukaryotic microbiology, 40(6), 800-4","doi":null,"pmid":"7904878","tags":["opioid-peptides","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Tetrahymena has a functional opioid receptor that inhibits phagocytosis. Morphine most potent, beta-endorphin second. Naloxone-reversible. Receptor predates nervous systems.","whyItMatters":"Finding opioid receptors in a single-celled organism means this signaling system is far more ancient than previously thought. It evolved long before there were nervous systems or pain perception.","specificNumbers":"","methodology":"Phagocytosis assays in Tetrahymena with various mammalian opioid agonists and antagonists. Intrinsic activity and potency rankings determined.","limitations":"Single-celled organism study. The Tetrahymena 'opioid receptor' may not be structurally identical to mammalian opioid receptors. Pharmacological similarity does not prove molecular identity."},{"rthcId":"RPEP-00261","title":"Endogenous opioid regulation of oxytocin secretion through pregnancy in the rat.","authors":"Douglas, A J; Dye, S; Leng, G; Russell, J A; Bicknell, R J","year":1993,"journal":"Journal of neuroendocrinology, 5(3), 307-14","doi":null,"pmid":"8100468","tags":["opioid-peptides","fertility","oxytocin"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Naloxone significantly increased plasma oxytocin on days 15, 18, and 21 of pregnancy but not in non-pregnant, early pregnant, or post-partum rats.","whyItMatters":"This reveals a natural mechanism that prevents premature labor. The body's opioid peptides suppress oxytocin during pregnancy. When this brake is released, labor can proceed.","specificNumbers":"","methodology":"Conscious rats were blood-sampled at multiple pregnancy stages. Naloxone or vehicle was injected, and plasma oxytocin was measured by radioimmunoassay.","limitations":"Animal study in rats. Rat pregnancy is shorter than human. The specific opioid peptides involved were not identified. Clinical translation needs confirmation."},{"rthcId":"RPEP-00262","title":"Characterization of non-opioid [3H]dynorphin A-(1-13) binding sites in the rat heart.","authors":"Dumont, M; Lemaire, S","year":1993,"journal":"Journal of molecular and cellular cardiology, 25(8), 983-91","doi":null,"pmid":"7903402","tags":["opioid-peptides","cardiovascular","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Rat heart has a non-opioid dynorphin A(1-13) binding site: Kd 285 nM, Bmax 215 pmol/mg protein. Trypsin-sensitive. Inhibited by Zn2+ and Mg2+. Standard opioid ligands do not compete.","whyItMatters":"The heart responding to dynorphin through a non-opioid receptor means opioid peptides affect the heart in ways that standard opioid drugs cannot block or mimic. This could explain some cardiac effects of opioid peptides.","specificNumbers":"","methodology":"Membrane binding assays using tritiated dynorphin A(1-13) on rat heart membrane preparations. Competition studies with opioid and non-opioid ligands. Characterization with enzyme treatment and divalent cations.","limitations":"In vitro binding study. Shows receptor presence but not function. The biological effects of activating this non-opioid site were not tested. Rat heart may differ from human."},{"rthcId":"RPEP-00263","title":"Relationship between plasma atrial natriuretic factor and opioid peptide levels in healthy subjects and in patients with acute congestive heart failure.","authors":"Fontana, F; Bernardi, P; Pich, E M; Capelli, M; Bortoluzzi, L; Spampinato, S; Canossa, M","year":1993,"journal":"European heart journal, 14(2), 219-25","doi":null,"pmid":"8095454","tags":["opioid-peptides","natriuretic-peptides","cardiovascular"],"studyType":"cross-sectional","evidenceStrength":"moderate","keyFinding":"ANF, beta-endorphin, met-enkephalin, dynorphin, and noradrenaline were all elevated in acute CHF. Higher levels correlated with greater severity.","whyItMatters":"Heart failure activates multiple peptide systems. Understanding this coordinated response could lead to better biomarker panels for assessing heart failure severity and guiding treatment.","specificNumbers":"","methodology":"Plasma samples from 20 acute CHF patients (stratified by severity) and 20 controls were analyzed for ANF, three opioid peptides, and noradrenaline by immunoassay.","limitations":"Cross-sectional study with relatively small groups. Plasma levels measured at one time point. Cannot determine if elevated opioids are beneficial or harmful."},{"rthcId":"RPEP-00264","title":"Growth hormone response in man to L-692,429, a novel nonpeptide mimic of growth hormone-releasing peptide-6.","authors":"Gertz, B J; Barrett, J S; Eisenhandler, R; Krupa, D A; Wittreich, J M; Seibold, J R; Schneider, S H","year":1993,"journal":"The Journal of clinical endocrinology and metabolism, 77(5), 1393-7","doi":null,"pmid":"8077339","tags":["ghrp","hormone-optimization"],"studyType":"RCT","evidenceStrength":"strong","keyFinding":"L-692,429 (0.001-1.0 mg/kg IV) produced dose-dependent GH release in healthy young men. At 1 mg/kg, response was comparable to GHRH-(1-29). Safe and well tolerated.","whyItMatters":"This proved that small molecules can activate the same receptor as growth hormone-releasing peptides. It paved the way for oral GH secretagogues like MK-677 (ibutamoren).","specificNumbers":"","methodology":"Double-blind, placebo-controlled, incremental dose study in 24 healthy non-obese males aged 18-26. L-692,429 given as 15-min IV infusion. GH measured serially. Safety monitoring included.","limitations":"Small phase I study in healthy young men only. Short-term safety only. IV route not practical for clinical use. Did not test repeated dosing or older populations."},{"rthcId":"RPEP-00265","title":"Decreased cerebrospinal fluid beta-endorphin and increased pain sensitivity in patients with functional abdominal pain.","authors":"Jørgensen, L S; Bach, F W; Christiansen, P; Raundahl, U; Ostgaard, S; Ekman, R","year":1993,"journal":"Scandinavian journal of gastroenterology, 28(9), 763-6","doi":null,"pmid":"7901892","tags":["opioid-peptides","pain","gut-healing"],"studyType":"cross-sectional","evidenceStrength":"moderate","keyFinding":"CSF beta-endorphin was significantly decreased in functional abdominal pain patients. Met-enkephalin and dynorphin were unchanged. Pain sensitivity was increased.","whyItMatters":"This provides biological evidence that functional abdominal pain involves a real deficit in the body's pain-control system, not just a psychological problem.","specificNumbers":"","methodology":"CSF was collected from 9 functional abdominal pain patients and 9 controls during spinal analgesia for minor surgery. Three opioid peptides were measured by RIA. Pain sensitivity was tested.","limitations":"Very small sample (9 per group). Cross-sectional design cannot prove causation. Controls were surgical patients, not completely healthy. Only one CSF sample per patient."},{"rthcId":"RPEP-00266","title":"Adrenomedullin: a novel hypotensive peptide isolated from human pheochromocytoma.","authors":"Kitamura, K; Kangawa, K; Kawamoto, M; Ichiki, Y; Nakamura, S; Matsuo, H; Eto, T","year":1993,"journal":"Biochemical and biophysical research communications, 192(2), 553-60","doi":null,"pmid":"8387282","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00267","title":"Lead toxicity and alterations in opioid systems.","authors":"Kitchen, I","year":1993,"journal":"Neurotoxicology, 14(2-3), 115-24","doi":null,"pmid":"8247386","tags":["opioid-peptides","neuropeptides","peptide-safety"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Lead exposure alters brain opioid peptide concentrations and receptor binding across multiple brain regions, potentially explaining neurological toxicity symptoms.","whyItMatters":"Lead poisoning remains a major global health problem, especially for children. Understanding that it disrupts the opioid system helps explain its neurological effects and could guide treatment.","specificNumbers":"","methodology":"Review of published studies on lead effects on opioid peptide levels, receptor binding, and related physiological functions in animals and humans.","limitations":"Review from 1993. Some findings were from high-dose animal studies that may not reflect typical human exposures. The specific mechanisms linking lead to opioid disruption were not fully characterized."},{"rthcId":"RPEP-00268","title":"A single residue, aspartic acid 95, in the delta opioid receptor specifies selective high affinity agonist binding.","authors":"Kong, H; Raynor, K; Yasuda, K; Moe, S T; Portoghese, P S; Bell, G I; Reisine, T","year":1993,"journal":"The Journal of biological chemistry, 268(31), 23055-8","doi":null,"pmid":"8226821","tags":["opioid-peptides","receptor-signaling","peptide-design"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Asp95Asn mutation in delta opioid receptor eliminated selective high-affinity agonist binding while preserving antagonist binding. Single residue determines agonist selectivity.","whyItMatters":"Knowing exactly which amino acid controls agonist selectivity enables rational design of new opioid drugs with specific receptor preferences, potentially reducing side effects.","specificNumbers":"","methodology":"Site-directed mutagenesis of the cloned delta opioid receptor. Mutant and wild-type receptors expressed in cells. Binding assays with selective agonists and antagonists.","limitations":"In vitro study using expressed receptors in cell lines. Single point mutation may have additional uncharacterized effects. Does not demonstrate in vivo consequences."},{"rthcId":"RPEP-00269","title":"In vivo stimulation of connective tissue accumulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ in rat experimental wounds.","authors":"Maquart, F X; Bellon, G; Chaqour, B; Wegrowski, J; Patt, L M; Trachy, R E; Monboisse, J C; Chastang, F; Birembaut, P; Gillery, P","year":1993,"journal":"The Journal of clinical investigation, 92(5), 2368-76","doi":null,"pmid":"8227353","tags":["ghk-cu","wound-healing","skin-repair"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"GHK-Cu significantly stimulated connective tissue accumulation and collagen synthesis in rat wounds in vivo, confirming its wound-healing potential first observed in cell culture.","whyItMatters":"This was the first in vivo demonstration that GHK-Cu could accelerate wound healing, validating its transition from a lab curiosity to a potential therapeutic agent for tissue repair.","specificNumbers":"","methodology":"Researchers used an established wound chamber model in rats, applying GHK-Cu directly to wounds and measuring connective tissue accumulation, collagen content, and blood vessel formation compared to controls.","limitations":"Animal study in rats using a wound chamber model, which may not perfectly replicate natural wound healing. No human data. Specific quantitative results not detailed in abstract."},{"rthcId":"RPEP-00270","title":"Changes in the levels of several endogenous opioid peptides in dog cerebrospinal fluid following morphine administration.","authors":"Natsuki, R; Dewey, W L","year":1993,"journal":"Arukoru kenkyu to yakubutsu izon = Japanese journal of alcohol studies & drug dependence, 28(5), 379-93","doi":null,"pmid":"8267521","tags":["opioid-peptides","addiction","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Morphine produced distinct changes in multiple CSF opioid peptide species, with patterns differing from plasma changes. HPLC confirmed specific peptide identification.","whyItMatters":"Understanding how morphine changes the brain's own opioid peptide levels helps explain tolerance, dependence, and why morphine's effects change with repeated use.","specificNumbers":"","methodology":"Dogs received CSF sampling via cisterna magna before and after SC morphine (10 mg/kg). CSF fractionated by gel filtration and HPLC. Opioid bioassay and radioimmunoassay used.","limitations":"Animal study in anesthetized dogs. Anesthesia affects opioid systems. Only one dose and time point. CSF from cisterna magna may not reflect all brain regions."},{"rthcId":"RPEP-00271","title":"Modulation of non-adrenergic non-cholinergic inhibitory transmission in rat duodenum: role of opiates and 5-hydroxytryptamine.","authors":"Postorino, A; Serio, R; Mulè, F; Adamo, E B; Di Giovanni, G; Marini, R","year":1993,"journal":"Archives italiennes de biologie, 131(2-3), 235-43","doi":null,"pmid":"8101707","tags":["opioid-peptides","gut-healing","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Opioid peptides acting through all three receptor types (mu, delta, kappa) enhance non-adrenergic non-cholinergic inhibitory responses in the duodenum, while serotonin reduces them.","whyItMatters":"Understanding how opioid peptides regulate gut motility helps explain both the constipating effects of opioid drugs and the potential role of endogenous opioid peptides in gut function disorders.","specificNumbers":"","methodology":"In vitro experiments using isolated rat duodenal segments with electrical field stimulation in the presence of atropine and guanethidine (to block standard pathways). Dose-response curves were generated for opioid agonists (DAGO, DPDPE, dynorphin) and serotonin.","limitations":"In vitro study using isolated rat gut tissue. Results may not directly translate to intact gut physiology or human intestinal function."},{"rthcId":"RPEP-00272","title":"Effect of synthetic thymic hormones on the cocaine-induced inhibition of the primary immune response in mice.","authors":"Ravagnan, G; Falchetti, R; Lanzilli, G; Di Francesco, P; Gaziano, R; Favalli, C; Garaci, E","year":1993,"journal":"International journal of immunopharmacology, 15(8), 879-85","doi":null,"pmid":"8253538","tags":["thymosin-alpha-1","immune-function","addiction"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Thymosin alpha 1 fully restored cocaine-suppressed antibody responses. Thymopentin partially restored them. Effect confirmed at the individual splenocyte level.","whyItMatters":"Drug users are vulnerable to infections due to immune suppression. Thymic peptides could help restore immune function in people using cocaine or other immunosuppressive drugs.","specificNumbers":"","methodology":"Mice received cocaine from day -4 to day 0 (immunization day). Thymosin alpha 1 or thymopentin given concurrently. Antibody response to SRBC measured at day 5 by hemolysis assay.","limitations":"Mouse study with a specific immunization model. Cocaine dosing may not reflect human use patterns. Only humoral immunity tested."},{"rthcId":"RPEP-00273","title":"Chronic intracerebroventricular infusion of the antiopioid peptide, Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2 (NPFF), downregulates mu opioid binding sites in rat brain.","authors":"Rothman, R B; Brady, L S; Xu, H; Long, J B","year":1993,"journal":"Peptides, 14(6), 1271-7","doi":null,"pmid":"8134310","tags":["opioid-peptides","receptor-signaling","addiction"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Chronic ICV NPFF (5 micrograms/h for 10 days) downregulated mu opioid binding sites. Dynorphin and enkephalin mRNA were unchanged.","whyItMatters":"The brain has its own anti-opioid system (NPFF) that can reduce opioid receptor numbers. This natural balancing mechanism could be harnessed for treating opioid addiction.","specificNumbers":"","methodology":"Rats received continuous ICV infusion of NPFF or saline for 10 days via osmotic minipumps. Mu opioid receptor binding measured by autoradiography. Dynorphin and enkephalin mRNA measured by in situ hybridization.","limitations":"Animal study with chronic brain infusion. Supraphysiological NPFF doses. Functional consequences of mu receptor downregulation not tested. Only one time point examined."},{"rthcId":"RPEP-00274","title":"Phenylpiperidine opioid antagonists that promote weight loss in rats have high affinity for the kappa 2B (enkephalin-sensitive) binding site.","authors":"Rothman, R B; Xu, H; Char, G U; Kim, A; De Costa, B R; Rice, K C; Zimmerman, D M","year":1993,"journal":"Peptides, 14(1), 17-20","doi":null,"pmid":"8382809","tags":["opioid-peptides","weight-loss","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Weight-loss-promoting phenylpiperidine antagonists like LY255582 had high affinity for the kappa-2B binding site. Non-weight-loss compounds did not.","whyItMatters":"This identifies a specific opioid receptor subsite involved in appetite and weight control. Targeting this site could lead to new weight loss drugs.","specificNumbers":"","methodology":"Phenylpiperidine opioid antagonists were tested for receptor binding at multiple opioid binding sites and compared based on their weight loss efficacy in lean and obese Zucker rats.","limitations":"Animal study with binding data. Kappa-2B subtype classification was debated and not universally accepted. Mechanism of weight loss not fully established."},{"rthcId":"RPEP-00275","title":"Opioid peptide gene expression in the nucleus tractus solitarius of rat brain and increases induced by unilateral cervical vagotomy: implications for role of opioid neurons in respiratory control mechanisms.","authors":"Rutherfurd, S D; Gundlach, A L","year":1993,"journal":"Neuroscience, 57(3), 797-810","doi":null,"pmid":"7906015","tags":["opioid-peptides","respiratory","neuropeptides"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Proenkephalin and prodynorphin mRNA found in NTS and other medullary nuclei. Unilateral vagotomy increased opioid mRNA in ipsilateral NTS.","whyItMatters":"Opioid peptides in the brain's breathing center help explain why opioid drugs can suppress breathing. Understanding this system could help develop safer pain drugs.","specificNumbers":"","methodology":"In situ hybridization with DNA probes for proenkephalin and prodynorphin in rat medulla oblongata. Unilateral cervical vagotomy performed; NTS analyzed bilaterally.","limitations":"Animal study mapping mRNA, not protein or function. Vagotomy is a severe intervention. Only one time point after nerve cutting."},{"rthcId":"RPEP-00276","title":"CSF neuropeptides in cancer pain: effects of spinal opioid therapy.","authors":"Samuelsson, H; Ekman, R; Hedner, T","year":1993,"journal":"Acta anaesthesiologica Scandinavica, 37(5), 502-8","doi":null,"pmid":"8356865","tags":["opioid-peptides","pain","neuropeptides","cancer"],"studyType":"cross-sectional","evidenceStrength":"moderate","keyFinding":"Cancer pain patients had altered CSF neuropeptide profiles. Spinal opioid therapy changed pain scores and further modified CSF peptide levels.","whyItMatters":"Effective pain treatment changes the spinal cord's chemical environment, not just pain perception. This could help optimize pain treatment by monitoring neuropeptide responses.","specificNumbers":"","methodology":"CSF collected from 10 cancer pain patients before and after spinal opioid therapy initiation, and from 10 controls. Seven neuropeptides measured by radioimmunoassay. Pain rated by VAS.","limitations":"Small study (10 patients). No placebo control for the opioid therapy. CSF sampling is invasive. Multiple peptides measured increases chance of false positives."},{"rthcId":"RPEP-00277","title":"Mu- and delta-opioid receptors inhibitorily linked to dopamine-sensitive adenylate cyclase in rat striatum display a selectivity profile toward endogenous opioid peptides different from that of presynaptic mu, delta and kappa receptors.","authors":"Schoffelmeer, A N; De Vries, T J; Hogenboom, F; Mulder, A H","year":1993,"journal":"The Journal of pharmacology and experimental therapeutics, 267(1), 205-10","doi":null,"pmid":"8229747","tags":["opioid-peptides","receptor-signaling","neuropeptides"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Post-synaptic mu/delta receptors inhibiting DA-stimulated adenylate cyclase showed different endogenous peptide affinity profiles than presynaptic mu, delta, and kappa receptors.","whyItMatters":"The same opioid peptide can have different effects depending on which receptor population it reaches. This explains some of the complexity and unpredictability of opioid drug effects.","specificNumbers":"","methodology":"Rat striatal slices superfused with dopamine. Opioid peptides tested for ability to inhibit DA D1-stimulated adenylate cyclase (postsynaptic) vs. presynaptic modulation. Peptidase inhibitors included.","limitations":"In vitro brain slice study. Complex pharmacology with multiple simultaneous drug exposures. Conditions may not perfectly reflect in vivo signaling."},{"rthcId":"RPEP-00278","title":"Hepatoprotective effect of BPC 157, a 15-amino acid peptide, on liver lesions induced by either restraint stress or bile duct and hepatic artery ligation or CCl4 administration. A comparative study with dopamine agonists and somatostatin.","authors":"Sikiric, P; Seiwerth, S; Grabarevic, Z; Rucman, R; Petek, M; Rotkvic, I; Turkovic, B; Jagic, V; Mildner, B; Duvnjak, M","year":1993,"journal":"Life sciences, 53(18), PL291-6","doi":null,"pmid":"7901724","tags":["bpc-157","liver","gut-healing"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"BPC 157 prevented liver necrosis and fatty changes in bile duct ligation, restraint stress, and CCl4 models. Effective orally and intraperitoneally. Outperformed bromocriptine, amantadine, and somatostatin.","whyItMatters":"BPC 157's liver protection across multiple injury types suggests a broad protective mechanism. Its oral effectiveness is especially important because it means the peptide could be taken as a pill.","specificNumbers":"","methodology":"Rats were subjected to bile duct + hepatic artery ligation, 48-hour restraint stress, or CCl4 administration. BPC 157 was given intragastrically or intraperitoneally. Liver tissue was examined histologically.","limitations":"Animal study in rats. Three acute/subacute injury models may not represent chronic liver disease. Mechanism of protection not identified. No dose-response data presented in abstract."},{"rthcId":"RPEP-00279","title":"A new gastric juice peptide, BPC. An overview of the stomach-stress-organoprotection hypothesis and beneficial effects of BPC.","authors":"Sikirić, P; Petek, M; Rucman, R; Seiwerth, S; Grabarević, Z; Rotkvić, I; Turković, B; Jagić, V; Mildner, B; Duvnjak, M","year":1993,"journal":"Journal of physiology, Paris, 87(5), 313-27","doi":null,"pmid":"8298609","tags":["bpc-157","gut-healing","inflammation"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"BPC 157 from gastric juice shows broad organoprotection across multiple stress models. The stomach may initiate a body-wide protective response during stress via peptide mediators.","whyItMatters":"If the stomach produces peptides that protect the entire body during stress, this changes how we think about stress-related diseases and suggests new treatment approaches using stomach-derived peptides.","specificNumbers":"","methodology":"Review of experimental studies on BPC 157's protective effects across multiple organ systems and stress models, presented in the context of a novel hypothesis about stomach-mediated stress protection.","limitations":"Hypothesis-driven review based largely on the authors' own research. The organoprotection hypothesis was novel and not yet independently validated. All evidence from animal studies."},{"rthcId":"RPEP-00280","title":"Local analgesic effect of endogenous opioid peptides.","authors":"Stein, C; Hassan, A H; Lehrberger, K; Giefing, J; Yassouridis, A","year":1993,"journal":"Lancet (London, England), 342(8867), 321-4","doi":null,"pmid":"8101583","tags":["opioid-peptides","pain","inflammation","immune-function"],"studyType":"cross-sectional","evidenceStrength":"strong","keyFinding":"All three opioid peptides found in synovial immune cells. Intra-articular naloxone increased post-surgical knee pain, proving endogenous opioids provide functional local analgesia.","whyItMatters":"This proves the human body produces its own painkillers right inside inflamed joints. This landmark finding supports developing peripheral opioid treatments that work locally without brain side effects.","specificNumbers":"","methodology":"8 patients undergoing arthroscopic knee surgery. Synovial tissue examined by immunohistochemistry for opioid peptides. Separate patient group received intra-articular naloxone vs. saline post-surgery. Pain measured by VAS.","limitations":"Small sample (8 patients for histology). Only knee joint studied. Post-surgical inflammation may differ from chronic joint disease. Short-term pain assessment."},{"rthcId":"RPEP-00281","title":"Spinal involvement of both dynorphin A and Met-enkephalin in the antinociception induced by intracerebroventricularly administered bremazocine but not morphine in the mouse.","authors":"Tseng, L F; Collins, K A","year":1993,"journal":"The Journal of pharmacology and experimental therapeutics, 266(3), 1430-8","doi":null,"pmid":"8103794","tags":["opioid-peptides","pain","neuropeptides"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Spinal dynorphin A and met-enkephalin mediate bremazocine's pain relief but not morphine's, showing distinct opioid signaling pathways.","whyItMatters":"This study shows that different opioid drugs recruit different natural pain peptides in the spinal cord. Understanding these distinct pathways could help develop pain treatments with fewer side effects.","specificNumbers":"","methodology":"Researchers injected bremazocine or morphine into mouse brains (intracerebroventricular). They then gave antibodies against specific opioid peptides into the spinal cord to see which peptides were needed for pain relief, measured by the tail-flick test.","limitations":"This was an animal study in mice using direct brain injection, a route not used in humans. Results may not translate directly to human pain treatment."},{"rthcId":"RPEP-00282","title":"Receptor-selective opioid peptides fail to affect behavioral responses induced by a low dose of apomorphine in the mouse.","authors":"Ukai, M; Toyoshi, T; Kameyama, T","year":1993,"journal":"Pharmacology, biochemistry, and behavior, 46(3), 587-91","doi":null,"pmid":"7904071","tags":["opioid-peptides","neuropeptides","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Receptor-selective opioid peptides (DAMGO, dynorphin A, DPLPE) had no effect on low-dose apomorphine-induced behavioral suppression.","whyItMatters":"Understanding whether opioid and dopamine systems interact at the receptor level helps clarify how these two major brain signaling systems work together or independently.","specificNumbers":"","methodology":"Researchers injected mice with low-dose apomorphine (0.03 mg/kg) to suppress behavior, then gave intracerebroventricular injections of receptor-selective opioid peptides. They measured circling, rearing, and locomotion.","limitations":"Animal study in mice with direct brain injection. Tested only one dose of each opioid peptide. The lack of effect could reflect dose or timing issues rather than true absence of interaction."},{"rthcId":"RPEP-00283","title":"Possible opioid receptor function changes in isolated atria of the spontaneously hypertensive rat.","authors":"Wong, S C; Ingenito, A J","year":1993,"journal":"General pharmacology, 24(6), 1483-90","doi":null,"pmid":"8112524","tags":["opioid-peptides","cardiovascular","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Leu-enkephalin at 0.2 micromolar increased spontaneous beating rate in SHR atria but not in normal rat atria, across ages 4 to 16 weeks.","whyItMatters":"If opioid receptors work differently in hypertensive hearts, this could reveal new targets for blood pressure or heart rate treatments.","specificNumbers":"","methodology":"Researchers isolated right atria from hypertensive and normal rats at ages 4, 8, 12, and 16 weeks. They applied opioid peptides (beta-endorphin, dynorphin, met-enkephalin, DAGO, DADLE, leu-enkephalin) and measured spontaneous beating rate changes.","limitations":"Animal study using isolated rat heart tissue. The in vitro setting does not capture the full complexity of how opioid peptides work in a living animal. Only tested a narrow range of concentrations."},{"rthcId":"RPEP-00284","title":"Dynorphin modulates prolactin secretion in the turkey.","authors":"Youngren, O M; Silsby, J L; Phillips, R E; el Halawani, M E","year":1993,"journal":"General and comparative endocrinology, 91(2), 224-31","doi":null,"pmid":"8104840","tags":["opioid-peptides","hormone-optimization","fertility"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Big dynorphin (prodynorphin 209-240) caused a 5.1-fold increase in serum prolactin in turkeys, mediated through kappa opioid receptors.","whyItMatters":"Prolactin controls incubation behavior in birds and has wide-ranging hormonal effects in mammals. Understanding opioid control of prolactin helps explain how peptides regulate hormone systems.","specificNumbers":"","methodology":"Researchers infused opioid peptides (big dynorphin, dynorphin A, dynorphin B, beta-endorphin, met-enkephalin) into the third ventricle of anesthetized laying turkey hens and measured serum prolactin levels.","limitations":"Animal study in turkeys, not mammals. Used direct brain injection under anesthesia. Results may not apply to mammalian prolactin regulation or natural conditions."},{"rthcId":"RPEP-00285","title":"Effect of sulpiride or paroxetine on cerebrospinal fluid neuropeptide concentrations in patients with chronic tension-type headache.","authors":"Bach, F W; Langemark, M; Ekman, R; Rehfeld, J F; Schifter, S; Olesen, J","year":1994,"journal":"Neuropeptides, 27(2), 129-36","doi":null,"pmid":"7991067","tags":["neuropeptides","pain","opioid-peptides"],"studyType":"RCT","evidenceStrength":"moderate","keyFinding":"Sulpiride decreased CSF met-enkephalin while paroxetine increased it in chronic tension headache patients after 8 weeks of treatment.","whyItMatters":"Chronic tension headaches are common and hard to treat. Understanding how drugs change neuropeptide levels in the brain helps explain why some treatments work and guides development of better options.","specificNumbers":"","methodology":"Patients with chronic tension-type headache underwent lumbar puncture before and after 8 weeks of treatment with either sulpiride or paroxetine. CSF levels of beta-endorphin, met-enkephalin, dynorphin, CCK, CGRP, and somatostatin were measured.","limitations":"Small clinical study. Lumbar CSF may not perfectly reflect brain peptide levels at the sites that cause headaches. No placebo control group."},{"rthcId":"RPEP-00286","title":"Delta-opioid receptor agonists inhibit neuromuscular transmission in human colon.","authors":"Chamouard, P; Rohr, S; Meyer, C; Baumann, R; Angel, F","year":1994,"journal":"European journal of pharmacology, 262(1-2), 33-9","doi":null,"pmid":"7813576","tags":["opioid-peptides","gut-healing","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Delta opioid receptor agonists selectively inhibited nerve-stimulated contractions in human colon tissue without affecting spontaneous contractile activity.","whyItMatters":"Understanding how opioid receptors control colon nerve signaling helps explain opioid-related constipation and could lead to better treatments for gut motility disorders.","specificNumbers":"","methodology":"Researchers used superfused strips of human sigmoid colon (both longitudinal and circular muscle). They applied delta opioid agonists and measured spontaneous activity and responses to electrical nerve stimulation.","limitations":"In vitro study using human tissue samples. The isolated tissue setting does not fully replicate how the colon functions inside the body with its full nerve supply and hormonal environment."},{"rthcId":"RPEP-00287","title":"Opioid modulation of oxytocin release from spinal cord synaptosomes.","authors":"Daddona, M M; Haldar, J","year":1994,"journal":"Neuroreport, 5(14), 1833-5","doi":null,"pmid":"7827343","tags":["opioid-peptides","oxytocin","neuropeptides"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Naloxone (5 micromolar) enhanced potassium-evoked oxytocin release from spinal cord synaptosomes, showing tonic opioid inhibition of spinal oxytocin.","whyItMatters":"Oxytocin in the spinal cord plays roles in pain modulation and autonomic functions. Knowing that opioids regulate spinal oxytocin release adds a new layer to understanding pain and social behavior circuits.","specificNumbers":"","methodology":"Researchers prepared synaptosomes from thoracic and lumbosacral spinal cord of rats. They evoked oxytocin release with 56 mM KCl and measured how naloxone (opioid antagonist) changed the response.","limitations":"In vitro study using isolated rat spinal cord nerve endings. Cannot capture the full complexity of spinal cord signaling in a living animal."},{"rthcId":"RPEP-00288","title":"GH-releasing activity of Hexarelin, a new growth hormone releasing peptide, in infant and adult rats.","authors":"Deghenghi, R; Cananzi, M M; Torsello, A; Battisti, C; Muller, E E; Locatelli, V","year":1994,"journal":"Life sciences, 54(18), 1321-8","doi":null,"pmid":"7910650","tags":["ghrp","hormone-optimization","peptide-design"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Hexarelin effectively stimulated growth hormone secretion in both infant and adult rats through a non-GHRH pathway.","whyItMatters":"Growth hormone releasing peptides are used to boost natural GH production. Hexarelin's improved chemical stability made it a practical candidate for research and clinical development.","specificNumbers":"","methodology":"Researchers tested hexarelin in conscious 10-day-old and adult rats via intravenous and subcutaneous injection. They measured growth hormone levels and compared hexarelin to GHRP-6. They also tested it in rats with damaged GHRH neurons.","limitations":"Animal study in rats. Doses and responses in rats do not directly predict human dosing or effects. Long-term safety and efficacy not assessed."},{"rthcId":"RPEP-00289","title":"The third helix of the Antennapedia homeodomain translocates through biological membranes.","authors":"Derossi, D; Joliot, A H; Chassaing, G; Prochiantz, A","year":1994,"journal":"The Journal of biological chemistry, 269(14), 10444-50","doi":null,"pmid":"8144628","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00290","title":"Endogenous opioid system and atrial natriuretic factor in normotensive offspring of hypertensive parents at rest and during exercise test.","authors":"Fontana, F; Bernardi, P; Merlo Pich, E; Boschi, S; De Iasio, R; Capelli, M; Carboni, L; Spampinato, S","year":1994,"journal":"Journal of hypertension, 12(11), 1285-90","doi":null,"pmid":"7868876","tags":["opioid-peptides","natriuretic-peptides","cardiovascular"],"studyType":"cross-sectional","evidenceStrength":"preliminary","keyFinding":"Normotensive offspring of hypertensive parents showed altered opioid-ANF interactions during exercise, suggesting early neurohumoral changes before hypertension onset.","whyItMatters":"Finding hormonal differences before hypertension develops could help identify people at risk and potentially lead to early prevention strategies.","specificNumbers":"","methodology":"Researchers measured plasma beta-endorphin, met-enkephalin, dynorphin B, ANF, and noradrenaline in 8 offspring of hypertensive parents and 10 controls at rest and during exercise testing.","limitations":"Very small sample size (8 vs. 10). Cross-sectional design cannot prove these differences cause future hypertension. Single exercise session only."},{"rthcId":"RPEP-00291","title":"New dual inhibitors of neutral endopeptidase and angiotensin-converting enzyme: rational design, bioavailability, and pharmacological responses in experimental hypertension.","authors":"Fournié-Zaluski, M C; Coric, P; Turcaud, S; Rousselet, N; Gonzalez, W; Barbe, B; Pham, I; Jullian, N; Michel, J B; Roques, B P","year":1994,"journal":"Journal of medicinal chemistry, 37(8), 1070-83","doi":null,"pmid":"8164250","tags":["natriuretic-peptides","cardiovascular","peptide-design"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Orally active dual ACE/NEP inhibitors lowered blood pressure in hypertensive rats through combined angiotensin blockade and natriuretic peptide protection.","whyItMatters":"Combining two blood pressure-lowering mechanisms in one pill could provide better treatment than either alone. This approach eventually led to drugs like sacubitril/valsartan (Entresto) for heart failure.","specificNumbers":"","methodology":"Researchers used rational drug design to create dual inhibitors, tested their ability to block both enzymes in vitro, measured oral bioavailability, and assessed blood pressure effects in experimentally hypertensive rats.","limitations":"Animal study in rats. Oral bioavailability and efficacy in rats may not predict human pharmacology. Long-term safety not assessed."},{"rthcId":"RPEP-00292","title":"Augmenting effect of opioid peptides on murine macrophage activation.","authors":"Hagi, K; Uno, K; Inaba, K; Muramatsu, S","year":1994,"journal":"Journal of neuroimmunology, 50(1), 71-6","doi":null,"pmid":"7905488","tags":["opioid-peptides","immune-function","cancer"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Dynorphin-A enhanced macrophage tumoricidal activity under suboptimal activation conditions but not when fully activated.","whyItMatters":"Finding that opioid peptides can boost immune cell cancer-killing ability under certain conditions opens questions about how the opioid system affects cancer immunity.","specificNumbers":"","methodology":"Researchers treated mouse peritoneal macrophages with interferon and LPS at various concentrations, with or without opioid peptides (dynorphin-A, met-enkephalin, DAMGO, DADLE). Macrophage activation was measured by their ability to kill tumor cells.","limitations":"In vitro study using mouse macrophages. The artificial conditions of cell culture do not replicate the complex tumor environment in a living animal. The enhancement only occurred under suboptimal activation."},{"rthcId":"RPEP-00293","title":"Prodynorphin-derived peptide expression in primate cortex and striatum.","authors":"Healy, D J; Meador-Woodruff, J H","year":1994,"journal":"Neuropeptides, 27(5), 277-84","doi":null,"pmid":"7862260","tags":["opioid-peptides","neuropeptides","neuroprotection"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Alpha-neo-endorphin was the dominant prodynorphin peptide in primate brain, with striatal concentrations significantly exceeding cortical levels across all four peptides.","whyItMatters":"Knowing where dynorphin peptides are concentrated in the primate brain helps identify their roles in movement, emotion, pain, and neurological diseases.","specificNumbers":"","methodology":"Researchers measured dynorphin A (1-17), dynorphin A (1-8), dynorphin B, and alpha-neo-endorphin in 10 cortical regions and the striatum of old world monkeys (Macaca nemestrina) using radioimmunoassay.","limitations":"Descriptive mapping study without functional testing. Used a single primate species. Tissue-level measurements cannot reveal cell-type specificity."},{"rthcId":"RPEP-00294","title":"Antibacterial peptides and mitochondrial presequences affect mitochondrial coupling, respiration and protein import.","authors":"Hugosson, M; Andreu, D; Boman, H G; Glaser, E","year":1994,"journal":"European journal of biochemistry, 223(3), 1027-33","doi":null,"pmid":"8055943","tags":["antimicrobial-peptides","peptide-design","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Cecropins, magainin, and melittin disrupted mitochondrial coupling, protein import, and respiration, while PR-39 was nearly inert toward mitochondria.","whyItMatters":"If antimicrobial peptides damage human mitochondria, they could harm healthy cells. Finding that some peptides like PR-39 spare mitochondria helps guide the design of safer antimicrobial drugs.","specificNumbers":"","methodology":"Researchers isolated mitochondria and tested the effects of various antibacterial peptides on three functions: respiratory control (coupling), protein import, and respiration rates at increasing concentrations.","limitations":"In vitro study using isolated mitochondria. Does not account for how peptides behave inside living cells where other factors affect their access to mitochondria."},{"rthcId":"RPEP-00295","title":"Effects of acute and repeated intravenous administration of L-692,585, a novel non-peptidyl growth hormone secretagogue, on plasma growth hormone, IGF-1, ACTH, cortisol, prolactin, insulin, and thyroxine levels in beagles.","authors":"Jacks, T; Hickey, G; Judith, F; Taylor, J; Chen, H; Krupa, D; Feeney, W; Schoen, W; Ok, D; Fisher, M","year":1994,"journal":"The Journal of endocrinology, 143(2), 399-406","doi":null,"pmid":"7830002","tags":["ghrp","hormone-optimization","bioavailability"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"L-692,585 produced 4.3 to 7-fold increases in peak GH with maintained efficacy over 15 days of daily dosing and elevated IGF-1 by day 15.","whyItMatters":"Non-peptide GH secretagogues can be taken by mouth, unlike peptide versions that need injection. This study showed L-692,585 maintains its effect with repeated dosing, a key requirement for practical clinical use.","specificNumbers":"","methodology":"Eight beagle dogs received single IV doses of L-692,585 at three dose levels or saline in a balanced study. A separate group received daily doses for 15 days with GH, IGF-1, ACTH, cortisol, prolactin, insulin, and thyroxine measured.","limitations":"Animal study in dogs. Beagle GH physiology differs from humans. Only 15 days of repeated dosing was tested. Intravenous route used rather than oral."},{"rthcId":"RPEP-00296","title":"Behavioral effects of systemically administered mu and kappa opioid agonists in the squirrel monkey: peptides versus alkaloids.","authors":"Jones, D N; Holtzman, S G","year":1994,"journal":"Pharmacology, biochemistry, and behavior, 47(3), 421-6","doi":null,"pmid":"7911572","tags":["opioid-peptides","neuropeptides","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Peptide opioid agonists (DAMGO, dynorphin analog) were less potent than corresponding non-peptide agonists (morphine, U50,488) in modifying monkey behavior after intramuscular injection.","whyItMatters":"Understanding why peptide opioids are less effective by injection helps explain the bioavailability challenges that limit their clinical use and drives research into better delivery methods.","specificNumbers":"","methodology":"Squirrel monkeys on a fixed-interval schedule of stimulus termination received intramuscular injections of mu and kappa selective peptide and non-peptide opioid agonists. Response rate and temporal pattern (quarter-life) were measured.","limitations":"Animal study in squirrel monkeys. Intramuscular route may disadvantage peptides due to enzymatic degradation. Small number of compounds tested."},{"rthcId":"RPEP-00297","title":"Lactoferricin, a new antimicrobial peptide.","authors":"Jones, E M; Smart, A; Bloomberg, G; Burgess, L; Millar, M R","year":1994,"journal":"The Journal of applied bacteriology, 77(2), 208-14","doi":null,"pmid":"7961192","tags":["antimicrobial-peptides","infection","bioactive-food-peptides"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Lactoferricin B showed broad-spectrum bactericidal activity at low concentrations, with enhanced effectiveness at lower pH and against actively growing bacteria.","whyItMatters":"With antibiotic resistance growing, natural antimicrobial peptides from food sources like milk offer promising alternatives. Lactoferricin B is especially interesting because it comes from a common dietary protein.","specificNumbers":"","methodology":"Researchers determined minimum inhibitory and bactericidal concentrations of purified lactoferricin B against multiple bacterial species. They tested effects of growth phase, inoculum size, pH, and ionic strength.","limitations":"In vitro study only. Antibacterial activity in a test tube may not translate to effectiveness inside the body, where pH, salt levels, and other proteins can interfere."},{"rthcId":"RPEP-00298","title":"Treatment with GHRH(1-29)NH2 in children with idiopathic short stature induces a sustained increase in growth velocity.","authors":"Kirk, J M; Trainer, P J; Majrowski, W H; Murphy, J; Savage, M O; Besser, G M","year":1994,"journal":"Clinical endocrinology, 41(4), 487-93","doi":null,"pmid":"7955460","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"After 12 months of twice-daily subcutaneous GHRH(1-29)NH2 injections (20 μg/kg):\n\n- Mean height velocity increased from 4.8 cm/year to 7.2 cm/year (p=0.001) — a 50% improvement\n- Children who were growing slowest before treatment showed the most dramatic improvement, with some reaching normal growth velocity percentiles\n- Final height prediction increased by a mean of 3.4 cm (SD 2.6)\n- IGF-1 levels increased during treatment, as did fasting blood glucose and insulin\n- Overnight GH levels and GH responses to GHRH testing paradoxically fell during the 12 months of therapy\n- After stopping treatment, catch-down growth occurred in the first 3 months (HV 3.89 cm/year), though growth velocity returned to pre-treatment baseline by 6–12 months off therapy","whyItMatters":"Idiopathic short stature — being significantly short without any identifiable hormone deficiency — is a common pediatric concern with limited treatment options. This study showed that stimulating the body's own growth hormone system with a GHRH peptide could accelerate growth, offering a potentially more physiological approach than injecting growth hormone directly. However, the catch-down growth after stopping raises questions about long-term benefit.","specificNumbers":"","methodology":"Eighteen short pre-pubertal children (ages 4.3–11.0, 17 male) with idiopathic short stature and normal GH levels were treated with twice-daily subcutaneous GHRH(1-29)NH2 at 20 μg/kg for 12 months. Height was measured every 3 months. Overnight GH profiles and GHRH stimulation tests were performed at 0, 3, 6, and 12 months. Growth was also monitored for 12 months after stopping treatment. One patient was withdrawn for non-compliance.","limitations":"Small sample with only 18 children (17 male, 1 female), making it impossible to assess sex differences. No control group receiving placebo — growth was compared to pre-treatment rates. The catch-down growth after stopping suggests no permanent height gain may occur. Increased fasting glucose and insulin during treatment raises metabolic safety concerns for longer use. The study predates modern growth standards and statistical methods."},{"rthcId":"RPEP-00299","title":"Effects of a mixture of peptidase inhibitors (amastatin, captopril and phosphoramidon) on Met-enkephalin-, beta-endorphin-, dynorphin-(1-13)- and electroacupuncture-induced antinociception in rats.","authors":"Kishioka, S; Miyamoto, Y; Fukunaga, Y; Nishida, S; Yamamoto, H","year":1994,"journal":"Japanese journal of pharmacology, 66(3), 337-45","doi":null,"pmid":"7869621","tags":["opioid-peptides","pain","bioavailability"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Peptidase inhibitor mixture enhanced antinociception from met-enkephalin, beta-endorphin, and electroacupuncture, but not dynorphin-(1-13).","whyItMatters":"The body makes its own painkillers (opioid peptides) but enzymes break them down quickly. This study shows that blocking those enzymes can dramatically improve natural pain relief, pointing toward a drug strategy that works with the body rather than replacing its signals.","specificNumbers":"","methodology":"Rats received intrathecal injections of the peptidase inhibitor mixture (amastatin, captopril, phosphoramidon) followed by opioid peptides or electroacupuncture at the Hoku point. Pain threshold was measured by hind paw pressure test.","limitations":"Animal study in rats using spinal injection. The enzyme inhibitors were given directly into the spinal canal, not by mouth. The combination approach has not been tested in humans."},{"rthcId":"RPEP-00300","title":"Difference between plasma N- and C-terminally directed beta-endorphin immunoreactivity in infantile autism.","authors":"Leboyer, M; Bouvard, M P; Recasens, C; Philippe, A; Guilloud-Bataille, M; Bondoux, D; Tabuteau, F; Dugas, M; Panksepp, J; Launay, J M","year":1994,"journal":"The American journal of psychiatry, 151(12), 1797-801","doi":null,"pmid":"7977888","tags":["opioid-peptides","neuropeptides","neuroprotection"],"studyType":"cross-sectional","evidenceStrength":"moderate","keyFinding":"The N-terminal to C-terminal beta-endorphin ratio was significantly different in children with autism compared to healthy controls and children with Rett syndrome.","whyItMatters":"The opioid excess theory of autism has been debated for decades. This study provides specific evidence that beta-endorphin processing differs in autism, pointing toward a measurable biological marker.","specificNumbers":"","methodology":"Blood samples from 67 children with autism (meeting DSM-III-R and ICD-10 criteria), 22 girls with Rett syndrome, and 67 age-matched controls were tested using N-terminal and C-terminal directed radioimmunoassays for beta-endorphin.","limitations":"Cross-sectional study measuring blood levels only. Plasma beta-endorphin may not reflect brain levels. Cannot determine whether the difference is a cause or consequence of autism. The opioid theory of autism remains controversial."},{"rthcId":"RPEP-00301","title":"Palatability of a meal influences release of beta-endorphin, and of potential regulators of food intake in healthy human subjects.","authors":"Melchior, J C; Rigaud, D; Chayvialle, J A; Colas-Linhart, N; Laforest, M D; Petiet, A; Comoy, E; Apfelbaum, M","year":1994,"journal":"Appetite, 22(3), 233-44","doi":null,"pmid":"7979341","tags":["opioid-peptides","neuropeptides","weight-loss"],"studyType":"cross-sectional","evidenceStrength":"moderate","keyFinding":"A highly palatable meal significantly increased post-meal beta-endorphin, pancreatic polypeptide, and neurotensin compared to the same unpalatable meal.","whyItMatters":"This reveals that the pleasure of eating triggers opioid release. This opioid response may reinforce eating enjoyable foods and could help explain why palatable food is harder to stop eating.","specificNumbers":"","methodology":"Healthy human subjects ate either a highly palatable or unpalatable version of the same meal, or fasted. Blood was sampled over 3 hours for beta-endorphin, pancreatic polypeptide, neurotensin, CCK, insulin, glucose, and other markers.","limitations":"Small human study. Only compared two extremes of palatability with the same meal content. Short monitoring period. Individual variation in taste preferences not fully controlled."},{"rthcId":"RPEP-00302","title":"Voltage-dependent effects of opioid peptides on hippocampal CA3 pyramidal neurons in vitro.","authors":"Moore, S D; Madamba, S G; Schweitzer, P; Siggins, G R","year":1994,"journal":"The Journal of neuroscience : the official journal of the Society for Neuroscience, 14(2), 809-20","doi":null,"pmid":"7905518","tags":["opioid-peptides","neuroprotection","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Opioid peptides including dynorphins produced voltage-dependent changes in potassium currents in CA3 neurons, resolving contradictory findings from prior studies.","whyItMatters":"The hippocampus is critical for memory and learning. Understanding how opioid peptides modulate hippocampal neurons in a voltage-dependent manner helps explain their complex effects on cognition and memory.","specificNumbers":"","methodology":"Researchers used single-electrode voltage-clamp recording in rat hippocampal slices to test opioid effects on CA3 pyramidal neurons at controlled voltage levels.","limitations":"In vitro study using rat brain slices. The artificial recording conditions do not fully replicate how these neurons function in a living brain with all their normal inputs."},{"rthcId":"RPEP-00303","title":"Serum type III procollagen peptide, type IV collagen 7S domain, central triple-helix of type IV collagen and tissue inhibitor of metalloproteinases in patients with chronic viral liver disease: relationship to liver histology.","authors":"Murawaki, Y; Ikuta, Y; Koda, M; Kawasaki, H","year":1994,"journal":"Hepatology (Baltimore, Md.), 20(4 Pt 1), 780-7","doi":null,"pmid":"7927217","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00304","title":"Prospectives on the treatment of chronic hepatitis B and chronic hepatitis C with thymic peptides and antiviral agents.","authors":"Mutchnick, M G; Ehrinpreis, M N; Kinzie, J L; Peleman, R R","year":1994,"journal":"Antiviral research, 24(2-3), 245-57","doi":null,"pmid":"7526795","tags":["thymosin-alpha-1","immune-function","infection"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Thymosin alpha 1 demonstrated promising antiviral and immune-enhancing effects in early hepatitis B and C trials, suggesting it could complement or replace interferon.","whyItMatters":"In 1994, treatment options for chronic hepatitis were limited and poorly tolerated. Thymosin alpha 1 represented a new class of immune-based therapy that worked differently from antivirals.","specificNumbers":"","methodology":"Narrative review of published clinical trials and preclinical studies on thymic peptides and antiviral agents for chronic hepatitis B and C.","limitations":"Narrative review without systematic methodology. Based on early-stage clinical data that may not have been replicated. Treatment landscape for hepatitis has changed dramatically since 1994."},{"rthcId":"RPEP-00305","title":"Pharmacological characterization of the cloned kappa-, delta-, and mu-opioid receptors.","authors":"Raynor, K; Kong, H; Chen, Y; Yasuda, K; Yu, L; Bell, G I; Reisine, T","year":1994,"journal":"Molecular pharmacology, 45(2), 330-4","doi":null,"pmid":"8114680","tags":["opioid-peptides","receptor-signaling","peptide-design"],"studyType":"in-vitro","evidenceStrength":"strong","keyFinding":"Cloned kappa, delta, and mu opioid receptors showed distinct pharmacological profiles matching decades of predictions from classical pharmacology studies.","whyItMatters":"Cloning and characterizing all three opioid receptors was a breakthrough that enabled targeted drug design. It confirmed the receptor subtypes that govern pain, addiction, and mood regulation.","specificNumbers":"","methodology":"Researchers expressed cloned kappa, delta, and mu opioid receptors in cell lines and performed radioligand binding studies with a panel of opioid drugs and peptides to determine receptor selectivity profiles.","limitations":"In vitro binding studies in cell lines. Receptor behavior in isolated cells may not fully represent how receptors function in complex brain circuits with multiple interacting systems."},{"rthcId":"RPEP-00306","title":"Elevated cerebrospinal fluid levels of substance P in patients with the fibromyalgia syndrome.","authors":"Russell, I J; Orr, M D; Littman, B; Vipraio, G A; Alboukrek, D; Michalek, J E; Lopez, Y; MacKillip, F","year":1994,"journal":"Arthritis and rheumatism, 37(11), 1593-601","doi":null,"pmid":"7526868","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00307","title":"Interleukin 1 beta and corticotropin-releasing factor inhibit pain by releasing opioids from immune cells in inflamed tissue.","authors":"Schäfer, M; Carter, L; Stein, C","year":1994,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 91(10), 4219-23","doi":null,"pmid":"7910403","tags":["opioid-peptides","inflammation","pain","immune-function"],"studyType":"animal-study","evidenceStrength":"strong","keyFinding":"IL-1 beta and CRF caused immune cells in inflamed tissue to release opioid peptides that produced local pain relief, blocked by naloxone and anti-opioid antibodies.","whyItMatters":"This study proved that the immune system has a built-in pain relief mechanism at inflammation sites. This could lead to treatments that enhance natural pain relief without the side effects of systemic opioid drugs.","specificNumbers":"","methodology":"Researchers used a rat model of inflammatory pain (Freund's adjuvant in the paw). They injected IL-1 beta or CRF into the inflamed paw and measured pain thresholds. They also tested immune cell opioid release in vitro.","limitations":"Animal study in rats using an artificial inflammation model. The immune cell types and opioid peptides involved may differ in human inflammatory conditions."},{"rthcId":"RPEP-00308","title":"Opioid peptides in the pituitary: a hormone, a paracrine modulator and a peptide in search of a function.","authors":"Schäfer, M K; Martin, R","year":1994,"journal":"Biological chemistry Hoppe-Seyler, 375(11), 737-40","doi":null,"pmid":"7695835","tags":["opioid-peptides","hormone-optimization","neuropeptides"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Each opioid precursor family has a distinct role in the pituitary: beta-endorphin as a hormone, dynorphin as a paracrine modulator of oxytocin, and enkephalins as yet-uncharacterized players.","whyItMatters":"The pituitary controls many body systems through hormones. Understanding how opioid peptides modulate pituitary function helps explain their wide-ranging effects on stress, reproduction, and metabolism.","specificNumbers":"","methodology":"Narrative review of published literature on opioid peptide localization, release, and function in the mammalian pituitary gland.","limitations":"Narrative review based on available evidence as of 1994. Some proposed functions may have been confirmed or refuted by later research."},{"rthcId":"RPEP-00309","title":"The beneficial effect of BPC 157, a 15 amino acid peptide BPC fragment, on gastric and duodenal lesions induced by restraint stress, cysteamine and 96% ethanol in rats. A comparative study with H2 receptor antagonists, dopamine promotors and gut peptides.","authors":"Sikiric, P; Seiwerth, S; Grabarevic, Z; Petek, M; Rucman, R; Turkovic, B; Rotkvic, I; Jagic, V; Duvnjak, M; Mise, S","year":1994,"journal":"Life sciences, 54(5), PL63-8","doi":null,"pmid":"7904712","tags":["bpc-157","gut-healing","inflammation"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"BPC 157 was the only tested compound that consistently protected against gastric and duodenal ulcers in all three models, regardless of whether given before, during, or after ulcer induction.","whyItMatters":"BPC 157's consistent gut protection across multiple models and treatment timings suggests a robust protective mechanism. This study is one of the key early papers establishing BPC-157 as a gastric protective peptide.","specificNumbers":"","methodology":"Rats received BPC 157 (intraperitoneally or intragastrically) before, during, or after ulcer induction by 48-hour restraint stress, subcutaneous cysteamine, or intragastric 96% ethanol. Results were compared to H2 blockers, dopamine promotors, and gut peptides.","limitations":"Animal study in rats. The ulcer models are artificial and may not fully represent human peptic ulcer disease. This study is from the lab that discovered BPC 157, and independent replication is important."},{"rthcId":"RPEP-00310","title":"Plasticity in spinal opioid control of lower urinary tract function in paraplegic cats.","authors":"Thor, K B; Roppolo, J R; Kawatani, M; Erdman, S; deGroat, W C","year":1994,"journal":"Neuroreport, 5(13), 1673-8","doi":null,"pmid":"7819545","tags":["opioid-peptides","neuropeptides","neuroprotection"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Naloxone restored urinary function in chronic spinal cats but not acute ones, demonstrating opioid system plasticity that contributes to urinary retention after spinal cord injury.","whyItMatters":"Urinary problems are a major complication of spinal cord injury. Finding that the opioid system plays an increasing role over time suggests a treatable target for improving bladder function in people with chronic paralysis.","specificNumbers":"","methodology":"Researchers administered naloxone (5-500 micrograms/kg i.p.) to unanesthetized paraplegic cats with acute or chronic spinal cord injuries while monitoring bladder function and hind limb reflexes.","limitations":"Animal study in cats. The opioid system reorganization may differ between cats and humans. Only tested naloxone (a non-selective opioid blocker), so the specific receptor subtypes involved are unknown."},{"rthcId":"RPEP-00311","title":"Immunocytochemical evidence for the presence of Met-enkephalin and Leu-enkephalin in distinct neurons in the brain of the elasmobranch fish Scyliorhinus canicula.","authors":"Vallarino, M; Bucharles, C; Facchinetti, F; Vaudry, H","year":1994,"journal":"The Journal of comparative neurology, 347(4), 585-97","doi":null,"pmid":"7814676","tags":["opioid-peptides","neuropeptides","neuroprotection"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Both met-enkephalin and leu-enkephalin are present in separate neuron populations in the dogfish shark brain, but dynorphin-related peptides were not detected.","whyItMatters":"Finding enkephalins in such an ancient species confirms these opioid peptides play fundamental roles in brain function that have been preserved for hundreds of millions of years of evolution.","specificNumbers":"","methodology":"Immunohistochemical staining of dogfish shark (Scyliorhinus canicula) brain sections using antibodies against multiple opioid peptides to map their distribution.","limitations":"Single species study using immunohistochemistry, which can have cross-reactivity issues. Absence of staining does not definitively prove peptide absence."},{"rthcId":"RPEP-00312","title":"Peptides corresponding to a predictive alpha-helical domain of human immunodeficiency virus type 1 gp41 are potent inhibitors of virus infection.","authors":"Wild, C T; Shugars, D C; Greenwell, T K; McDanal, C B; Matthews, T J","year":1994,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 91(21), 9770-4","doi":null,"pmid":"7937889","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00313","title":"Autoradiographic localization of beta-endorphin binding in the pancreas.","authors":"Zhang, M; Zheng, M; Schleicher, R L","year":1994,"journal":"Molecular and cellular neurosciences, 5(6), 684-90","doi":null,"pmid":"7704443","tags":["opioid-peptides","diabetes","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Specific beta-endorphin binding sites were localized to pancreatic islet cells, blocked by mu and delta receptor ligands, confirming opioid receptors on insulin-producing cells.","whyItMatters":"If opioid receptors sit directly on insulin-producing cells, this creates a direct link between the opioid system and blood sugar control. This could help explain metabolic effects of opioid drugs.","specificNumbers":"","methodology":"Autoradiographic localization of 125I-labeled beta-endorphin binding in rabbit pancreas sections. Competition binding studies with opioid agonists and antagonists.","limitations":"In vitro study in rabbit tissue. The presence of binding sites does not prove functional significance. Rabbit pancreatic physiology differs from human."},{"rthcId":"RPEP-00314","title":"Conformational studies on model peptides with 1-aminocyclobutane 1-carboxylic acid residues.","authors":"Balaji, V N; Ramnarayan, K; Chan, M F; Rao, S N","year":1995,"journal":"Peptide research, 8(3), 178-86","doi":null,"pmid":"7670233","tags":["cyclic-peptides","peptide-design","bioavailability"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"ACBC-containing model peptides adopted characteristic stable conformations (helical and extended) that could be leveraged for peptide drug design.","whyItMatters":"One of the biggest challenges in peptide drug development is that peptides are floppy and easily broken down. Constrained building blocks like ACBC help solve both problems by locking peptides into stable, active shapes.","specificNumbers":"","methodology":"Molecular mechanics calculations on model peptides containing ACBC and its derivatives to determine low-energy conformations and compare them to natural amino acid peptides.","limitations":"Computational modeling study without experimental validation. Predicted conformations need to be confirmed by actual structural studies like NMR or X-ray crystallography."},{"rthcId":"RPEP-00315","title":"Cloning and functional expression of a human Y4 subtype receptor for pancreatic polypeptide, neuropeptide Y, and peptide YY.","authors":"Bard, J A; Walker, M W; Branchek, T A; Weinshank, R L","year":1995,"journal":"The Journal of biological chemistry, 270(45), 26762-5","doi":null,"pmid":"7592911","tags":["neuropeptides","weight-loss","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"strong","keyFinding":"The human Y4 receptor was cloned and shown to bind pancreatic polypeptide, NPY, and PYY, expanding the known receptor family for these appetite-regulating peptides.","whyItMatters":"NPY and related peptides are among the most powerful appetite stimulators known. Identifying their receptors is essential for developing drugs that could block excessive appetite or treat eating disorders.","specificNumbers":"","methodology":"Researchers used homology screening of a human placental genomic library to clone the Y4 receptor, then expressed it in cells and characterized its pharmacology using binding and functional assays.","limitations":"In vitro characterization of a cloned receptor. Cell-based expression may not fully represent how the receptor behaves in its natural tissue context."},{"rthcId":"RPEP-00316","title":"Effect of tripeptide-copper complexes on the process of skin wound healing and on cultured fibroblasts.","authors":"Buffoni, F; Pino, R; Dal Pozzo, A","year":1995,"journal":"Archives internationales de pharmacodynamie et de therapie, 330(3), 345-60","doi":null,"pmid":"8836453","tags":["ghk-cu","wound-healing","skin-repair"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"GHK-Cu increased wound collagen (hydroxyproline), protein, DNA, and amine oxidase activity in guinea pig skin wounds, with effects requiring the peptide component, not just copper.","whyItMatters":"GHK-Cu is widely used in skin care products. This study provides direct evidence of its wound-healing effects in living tissue, showing it actively stimulates the cells and molecules needed for tissue repair.","specificNumbers":"","methodology":"Guinea pig dorsal skin wounds were treated with GHK-Cu or analogs. Hydroxyproline, proteins, DNA, and amine oxidase were measured. Wounds were examined histologically. Parallel experiments tested fibroblast proliferation in culture.","limitations":"Animal study in guinea pigs. Wound healing in guinea pig skin may differ from human skin. Only tested topical application to fresh wounds, not aged or damaged skin."},{"rthcId":"RPEP-00317","title":"Opioid and anti-opioid peptides.","authors":"Cesselin, F","year":1995,"journal":"Fundamental & clinical pharmacology, 9(5), 409-33","doi":null,"pmid":"8617406","tags":["opioid-peptides","neuropeptides","pain"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"The review synthesizes opioid peptide pharmacology including the novel concept of anti-opioid peptides that counterbalance opioid effects and may drive tolerance.","whyItMatters":"Understanding both opioid and anti-opioid systems is crucial for developing better pain treatments. Anti-opioid peptides may explain why opioid drugs become less effective over time (tolerance).","specificNumbers":"","methodology":"Narrative review of published literature on opioid and anti-opioid peptide pharmacology, receptor characterization, and physiological roles.","limitations":"Narrative review from 1995. Some concepts have been refined or revised since publication. The epsilon receptor's existence remains debated."},{"rthcId":"RPEP-00318","title":"Endogenous opioid peptides suppress cytokine-mediated upregulation of HIV-1 expression in the chronically infected promonocyte clone U1.","authors":"Chao, C C; Gekker, G; Sheng, W S; Hu, S; Portoghese, P S; Peterson, P K","year":1995,"journal":"Advances in experimental medicine and biology, 373, 65-72","doi":null,"pmid":"7668162","tags":["opioid-peptides","immune-function","infection"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Met-enkephalin, dynorphin, and kappa agonist U50,488 suppressed IL-6-induced HIV-1 expression by over 40% in chronically infected monocyte cells.","whyItMatters":"Understanding how opioid peptides affect HIV is important because many HIV patients use opioid drugs for pain. This study suggests opioids might actually suppress viral activation in some immune cells.","specificNumbers":"","methodology":"U1 promonocyte cells chronically infected with HIV-1 were treated with opioid agonists with or without IL-6 stimulation. HIV-1 expression was measured by p24 antigen levels.","limitations":"In vitro study using a single cell line. The U1 cell model does not represent all HIV-infected cell types. Effects in a living person with a complex immune system may differ greatly."},{"rthcId":"RPEP-00319","title":"Central actions of peptide and non-peptide growth hormone secretagogues in the rat.","authors":"Dickson, S L; Leng, G; Dyball, R E; Smith, R G","year":1995,"journal":"Neuroendocrinology, 61(1), 36-43","doi":null,"pmid":"7731496","tags":["ghrp","hormone-optimization","neuropeptides"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Both GHRP-6 and non-peptide GH secretagogues activated Fos expression in the arcuate nucleus and excited arcuate neuroendocrine neurons, confirming central brain actions.","whyItMatters":"Knowing that GH secretagogues act on specific brain regions helps explain their effects beyond just growth hormone release, including appetite stimulation and sleep effects.","specificNumbers":"","methodology":"Rats received i.c.v. or i.v. injections of GHRP-6 or non-peptide GH secretagogues. Brain Fos expression was mapped by immunohistochemistry. Arcuate neuron electrophysiology was recorded in vivo.","limitations":"Animal study in rats. Fos expression shows activation but does not reveal the full functional significance. Brain activation patterns in rats may differ from humans."},{"rthcId":"RPEP-00320","title":"Nitrous oxide selectively releases Met5-enkephalin and Met5-enkephalin-Arg6-Phe7 into canine third ventricular cerebrospinal fluid.","authors":"Finck, A D; Samaniego, E; Ngai, S H","year":1995,"journal":"Anesthesia and analgesia, 80(4), 664-70","doi":null,"pmid":"7893015","tags":["opioid-peptides","pain","neuropeptides"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Nitrous oxide selectively increased met-enkephalin and met-enkephalin-Arg-Phe in third ventricular CSF without affecting beta-endorphin, leu-enkephalin, or dynorphin.","whyItMatters":"The mechanism of nitrous oxide analgesia has been debated for decades. This study provides the most direct evidence that it works through selective enkephalin release, resolving a long-standing controversy.","specificNumbers":"","methodology":"Eight acclimated dogs with chronically implanted third ventricle cannulae. CSF samples collected before and during nitrous oxide exposure. Five opioid peptides measured by radioimmunoassay.","limitations":"Animal study in dogs. CSF collection from the third ventricle may not reflect peptide changes in all brain regions. Only acute exposure was tested."},{"rthcId":"RPEP-00321","title":"Expression cloning and pharmacological characterization of a human hippocampal neuropeptide Y/peptide YY Y2 receptor subtype.","authors":"Gerald, C; Walker, M W; Vaysse, P J; He, C; Branchek, T A; Weinshank, R L","year":1995,"journal":"The Journal of biological chemistry, 270(45), 26758-61","doi":null,"pmid":"7592910","tags":["neuropeptides","weight-loss","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"strong","keyFinding":"The human Y2 receptor was cloned from hippocampus and shown to selectively bind NPY and PYY but not pancreatic polypeptide.","whyItMatters":"The Y2 receptor is a key regulator of appetite and is the target of PYY(3-36), a gut hormone that reduces food intake. Cloning it enabled development of anti-obesity drug candidates.","specificNumbers":"","methodology":"Expression cloning from a human hippocampal cDNA library. The receptor was expressed in cells and characterized using radioligand binding and functional assays.","limitations":"In vitro characterization of a cloned receptor. Receptor behavior in cell lines may not fully represent its function in brain circuits."},{"rthcId":"RPEP-00322","title":"[3H]naloxone binding sites in porcine ovarian follicles and corpora lutea during the ovarian cycle.","authors":"Hamada, H; Kishioka, S; Yamoto, M; Nakano, R","year":1995,"journal":"European journal of endocrinology, 132(5), 622-6","doi":null,"pmid":"7749506","tags":["opioid-peptides","fertility","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Specific opioid receptors were found in pig granulosa cells and corpora lutea, with receptor numbers increasing during follicular maturation.","whyItMatters":"Finding opioid receptors directly in the ovary means opioid peptides can regulate fertility at the organ level, not just through the brain. This has implications for understanding how opioid drugs affect reproductive function.","specificNumbers":"","methodology":"Radioligand binding using [3H]naloxone in porcine granulosa cells and corpus luteum subcellular fractions. Competition binding with beta-endorphin, met-enkephalin, and dynorphin.","limitations":"In vitro binding study in pig tissue. The functional significance of these receptors and their relevance to human ovarian biology need further study."},{"rthcId":"RPEP-00323","title":"Enhancement of phagocytosis by dynorphin A in mouse peritoneal macrophages.","authors":"Ichinose, M; Asai, M; Sawada, M","year":1995,"journal":"Journal of neuroimmunology, 60(1-2), 37-43","doi":null,"pmid":"7642746","tags":["opioid-peptides","immune-function","inflammation"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Dynorphin A dose-dependently enhanced macrophage phagocytosis through a naloxone-insensitive (non-opioid receptor) mechanism.","whyItMatters":"Dynorphin A has immune-boosting effects beyond its known role in pain. The non-opioid mechanism means these immune effects could potentially be harnessed without triggering opioid side effects.","specificNumbers":"","methodology":"Mouse peritoneal macrophage phagocytosis was measured by flow cytometry after treatment with dynorphin A and related peptides. Naloxone was used to test opioid receptor involvement.","limitations":"In vitro study using mouse macrophages. The non-opioid mechanism is not identified. Whether this effect occurs in living animals is unknown."},{"rthcId":"RPEP-00324","title":"Treatment of growth hormone-deficient adults with recombinant human growth hormone increases the concentration of growth hormone in the cerebrospinal fluid and affects neurotransmitters.","authors":"Johansson, J O; Larson, G; Andersson, M; Elmgren, A; Hynsjö, L; Lindahl, A; Lundberg, P A; Isaksson, O G; Lindstedt, S; Bengtsson, B A","year":1995,"journal":"Neuroendocrinology, 61(1), 57-66","doi":null,"pmid":"7537355","tags":["hormone-optimization","neuropeptides","opioid-peptides"],"studyType":"RCT","evidenceStrength":"strong","keyFinding":"One month of GH replacement increased CSF GH and IGF-1 while altering monoamine metabolites, neuropeptides, and opioid peptide concentrations.","whyItMatters":"GH-deficient adults report improved mood, energy, and cognition on GH replacement. This study provides the first direct evidence that GH treatment changes brain chemistry, offering a biological explanation for these improvements.","specificNumbers":"","methodology":"Double-blind, placebo-controlled trial in 20 adults with GH deficiency (10 per group). CSF collected before and after 1 month of treatment (0.25 U/kg/week). Measured GH, IGF-1, IGFBP-3, monoamine metabolites, neuropeptides, and opioid peptides.","limitations":"Small study (10 per group). Only 1 month of treatment. CSF sampling is invasive and may have affected some measurements. Long-term brain chemistry effects unknown."},{"rthcId":"RPEP-00325","title":"Growth hormone secretagogues. Clinical experience and therapeutic potential.","authors":"Laron, Z","year":1995,"journal":"Drugs, 50(4), 595-601","doi":null,"pmid":"8536548","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00326","title":"Regulation of cholecystokinin secretion by intraluminal releasing factors.","authors":"Liddle, R A","year":1995,"journal":"The American journal of physiology, 269(3 Pt 1), G319-27","doi":null,"pmid":"7573441","tags":["neuropeptides","gut-healing","bioactive-food-peptides"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Intraluminal peptide factors, released in response to dietary proteins and fats, are key regulators of CCK secretion that coordinate digestion.","whyItMatters":"CCK controls how we digest food. Understanding its release mechanisms is important for treating digestive disorders and for weight management, since CCK also signals fullness to the brain.","specificNumbers":"","methodology":"Narrative review of published research on CCK secretion mechanisms, luminal releasing factors, and their roles in digestive physiology.","limitations":"Narrative review from 1995. Some mechanisms have been further clarified since publication. The luminal releasing factors were not fully characterized at the time."},{"rthcId":"RPEP-00327","title":"Effects of endogenous opioid peptides and their analogs on the activities of hypothalamic arcuate neurons in brain slices from diestrous and ovariectomized rats.","authors":"Lin, J Y; Pan, J T","year":1995,"journal":"Brain research bulletin, 36(3), 225-33","doi":null,"pmid":"7697375","tags":["opioid-peptides","fertility","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"All tested opioid peptides inhibited arcuate neuron firing, with beta-endorphin affecting 55% of neurons, consistent across different hormonal states.","whyItMatters":"The arcuate nucleus controls GnRH release, which drives the entire reproductive hormone cascade. Opioid inhibition of these neurons explains how the opioid system suppresses fertility.","specificNumbers":"","methodology":"Brain slices from diestrous and ovariectomized rats. Extracellular single-unit recording of arcuate neurons during application of various opioid peptides and analogs.","limitations":"In vitro brain slice study in rats. Removed from the full hormonal environment of a living animal. Cannot distinguish which specific arcuate cell types are inhibited."},{"rthcId":"RPEP-00328","title":"Pituitary-adrenal activity and opioid release in ponies during thiopentone/halothane anaesthesia.","authors":"Luna, S P; Taylor, P M","year":1995,"journal":"Research in veterinary science, 58(1), 35-41","doi":null,"pmid":"7709057","tags":["opioid-peptides","hormone-optimization","neuropeptides"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Anesthesia triggered release of endogenous opioids, ACTH, vasopressin, cortisol, and catecholamines, with constant higher halothane producing more cardiovascular depression.","whyItMatters":"Understanding how anesthesia triggers opioid and stress hormone release helps veterinarians manage surgical pain and cardiovascular risks in horses, and has parallels to human anesthesiology.","specificNumbers":"","methodology":"Eleven ponies received thiopentone/halothane anesthesia. Six were maintained at constant 1.2% halothane, five at variable 0.8-1.2%. Blood hormones and cardiorespiratory parameters were monitored.","limitations":"Small veterinary study with 11 ponies. Two treatment groups with different protocols. Results may not directly apply to other species or anesthetic combinations."},{"rthcId":"RPEP-00329","title":"Tachykinins, sensory nerves, and asthma--an overview.","authors":"Lundberg, J M","year":1995,"journal":"Canadian journal of physiology and pharmacology, 73(7), 908-14","doi":null,"pmid":"8846429","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00330","title":"The outer membranes of Brucella spp. are resistant to bactericidal cationic peptides.","authors":"Martínez de Tejada, G; Pizarro-Cerdá, J; Moreno, E; Moriyón, I","year":1995,"journal":"Infection and immunity, 63(8), 3054-61","doi":null,"pmid":"7622230","tags":["antimicrobial-peptides","infection","immune-function"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Brucella species showed broad resistance to 14 antimicrobial peptides, with their outer membranes remaining intact and binding less antimicrobial peptide than susceptible bacteria.","whyItMatters":"Brucella causes a serious zoonotic disease. Understanding how it resists the body's antimicrobial peptide defenses explains its ability to survive inside the host and cause chronic infections.","specificNumbers":"","methodology":"Minimum inhibitory and bactericidal concentrations were tested for polymyxin B, defensins, lactoferricin B, cecropin, and other peptides against Brucella species and control bacteria. Membrane integrity was assessed by electron microscopy and permeability assays.","limitations":"In vitro study. Resistance in culture may not fully represent in vivo conditions where other immune mechanisms also act. Only tested against purified peptides, not whole immune cell killing."},{"rthcId":"RPEP-00331","title":"Growth hormone secretagogues: characterization, efficacy, and minimal bioactive conformation.","authors":"McDowell, R S; Elias, K A; Stanley, M S; Burdick, D J; Burnier, J P; Chan, K S; Fairbrother, W J; Hammonds, R G; Ingle, G S; Jacobsen, N E; Mortensen, D L; Rawson, T E; Won, W B; Clark, R G; Somers, T C","year":1995,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 92(24), 11165-9","doi":null,"pmid":"7479958","tags":["ghrp","peptide-design","hormone-optimization"],"studyType":"animal-study","evidenceStrength":"strong","keyFinding":"Novel backbone-modified GH secretagogues with molecular weight under 500 were the most potent reported, with confirmed anabolic efficacy and a defined bioactive conformation.","whyItMatters":"Identifying the smallest effective GH-releasing molecules means these compounds could potentially be made into pills. Understanding the exact 3D shape needed for activity guides all future GH secretagogue drug design.","specificNumbers":"","methodology":"Researchers altered GHRP backbone structure to create new compounds. These were tested in vitro for GH release and in vivo in rodents for anabolic effects. NMR was used to determine the 3D structure of a potent cyclic analog.","limitations":"Animal study in rodents. The most potent compounds may not maintain their potency in humans. Intermittent dosing was tested but long-term safety unknown."},{"rthcId":"RPEP-00332","title":"A role for hippocampal opioids in long-term functional plasticity.","authors":"Morris, B J; Johnston, H M","year":1995,"journal":"Trends in neurosciences, 18(8), 350-5","doi":null,"pmid":"7482797","tags":["opioid-peptides","neuroprotection","cognitive-enhancement"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Hippocampal dynorphins and enkephalins regulate synaptic transmission efficiency at granule cell synapses, with opioid levels changing dramatically under different physiological and pathological conditions.","whyItMatters":"The hippocampus is the brain's memory center. Understanding that opioid peptides modulate memory circuits helps explain cognitive effects of opioid drugs and opens targets for treating memory disorders.","specificNumbers":"","methodology":"Narrative review of published research on opioid peptide co-localization with glutamate in hippocampal granule cells and their role in long-term potentiation and synaptic plasticity.","limitations":"Review from 1995. Some proposed mechanisms have been refined by subsequent research. The relative contributions of enkephalins vs. dynorphins were not fully resolved."},{"rthcId":"RPEP-00333","title":"Analysis of i,i+5 and i,i+8 hydrophobic interactions in a helical model peptide bearing the hydrophobic staple motif.","authors":"Muñoz, V; Serrano, L","year":1995,"journal":"Biochemistry, 34(46), 15301-6","doi":null,"pmid":"7578146","tags":["peptide-design","cyclic-peptides","bioavailability"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Hydrophobic i,i+5 and i,i+8 interactions provide measurable stabilization to alpha-helix structures, with the hydrophobic staple motif contributing to helix nucleation.","whyItMatters":"Many peptide drugs need to be helical to work. Understanding which amino acid placements stabilize helices helps design more effective and stable peptide therapeutics.","specificNumbers":"","methodology":"Circular dichroism spectroscopy on designed alanine-based peptides with capping-box motifs. Helix/coil transition algorithms used to quantify interaction energies.","limitations":"Model peptide study in solution. The interactions measured in short isolated peptides may behave differently in full-length proteins or in cellular environments."},{"rthcId":"RPEP-00334","title":"The hydrophobic-staple motif and a role for loop-residues in alpha-helix stability and protein folding.","authors":"Muñoz, V; Blanco, F J; Serrano, L","year":1995,"journal":"Nature structural biology, 2(5), 380-5","doi":null,"pmid":"7664095","tags":["peptide-design","cyclic-peptides","bioavailability"],"studyType":"in-vitro","evidenceStrength":"strong","keyFinding":"The hydrophobic-staple motif (i,i+5 interaction at helix N-terminus) was discovered, validated by NMR, and shown to stabilize alpha-helices and define their N-terminal boundaries.","whyItMatters":"Understanding the fundamental rules of protein folding helps design better peptide drugs and predict protein structures. This motif is one of the building blocks of protein architecture.","specificNumbers":"","methodology":"Analysis of protein crystal structures to identify the motif pattern. NMR and circular dichroism of designed peptides to confirm the motif in solution. Comparison between peptide structures and protein helix termini.","limitations":"Identified in designed peptides and protein crystal structures. The quantitative contribution may vary in different protein contexts."},{"rthcId":"RPEP-00335","title":"An altered peptide ligand mediates immune deviation and prevents autoimmune encephalomyelitis.","authors":"Nicholson, L B; Greer, J M; Sobel, R A; Lees, M B; Kuchroo, V K","year":1995,"journal":"Immunity, 3(4), 397-405","doi":null,"pmid":"7584131","tags":["altered-peptide-ligand","autoimmune"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Researchers created a modified version of a myelin peptide (PLP 139-151) by changing a single amino acid — swapping tryptophan for glutamine at position 144. This altered peptide ligand (APL) prevented experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, when the disease was induced with the original peptide.\n\nThe APL worked by redirecting the immune response. Instead of producing inflammatory Th1 cells that attack myelin, the APL generated T cells that were cross-reactive with the original peptide but produced anti-inflammatory cytokines (IL-4 and IL-10) characteristic of Th2 and Th0 responses. When T cell lines generated with the APL were transferred to other animals, they protected against EAE.\n\nThis demonstrates that a single amino acid change in an antigenic peptide can fundamentally shift how the immune system responds — from destructive autoimmunity to protective tolerance.","whyItMatters":"This study demonstrated a powerful concept: you can take the very peptide that triggers an autoimmune attack and subtly modify it to redirect the immune system toward a protective response instead. This 'immune deviation' approach became a foundational strategy in peptide immunotherapy research for multiple sclerosis and other autoimmune diseases, showing that precision at the single amino acid level can flip the immune switch from attack to tolerance.","specificNumbers":"1 amino acid change (Trp→Gln at position 144) · Th2 shift (IL-4, IL-10 production) · Complete EAE prevention","methodology":"Researchers synthesized an altered peptide ligand (APL) of PLP 139-151 with a single substitution at the primary T cell receptor contact point. They tested whether the APL could prevent EAE in mice when co-administered with the disease-inducing native peptide. They characterized the T cell response by measuring cytokine profiles (Th1 vs Th2) and performed adoptive transfer experiments where APL-generated T cells were transferred to naive mice to test for protective effects.","limitations":"This is an animal model study using EAE in mice, which does not perfectly replicate human multiple sclerosis. The immune system in mice is simpler than in humans, and APL approaches that work in mice have had mixed results in human trials. The study does not address long-term durability of protection or potential safety risks of immune deviation."},{"rthcId":"RPEP-00336","title":"Processing of prodynorphin-derived peptides in striatal extracts. Identification by electrospray ionization mass spectrometry linked to size-exclusion chromatography.","authors":"Nylander, I; Tan-No, K; Winter, A; Silberring, J","year":1995,"journal":"Life sciences, 57(2), 123-9","doi":null,"pmid":"7603294","tags":["opioid-peptides","peptide-design","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Dynorphin B was processed to leu-enkephalin at a 10,000-fold higher rate than dynorphin A in rat striatal extracts.","whyItMatters":"The stability of a peptide determines how long it acts. Dynorphin A's resistance to breakdown means it has a much longer signaling window than dynorphin B, which is rapidly converted to a different opioid signal (enkephalin).","specificNumbers":"","methodology":"Synthetic dynorphin peptides were incubated with rat striatal extracts. Breakdown products were identified by size-exclusion chromatography connected to electrospray ionization mass spectrometry.","limitations":"In vitro study using brain tissue extracts. Degradation rates in isolated extracts may differ from rates in living brain tissue with active regulation."},{"rthcId":"RPEP-00337","title":"The effects of morphine treatment and morphine withdrawal on the dynorphin and enkephalin systems in Sprague-Dawley rats.","authors":"Nylander, I; Vlaskovska, M; Terenius, L","year":1995,"journal":"Psychopharmacology, 118(4), 391-400","doi":null,"pmid":"7568625","tags":["opioid-peptides","addiction","neuropeptides"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Chronic morphine increased dynorphin A and B in the nucleus accumbens and met-enkephalin in the striatum, with distinct withdrawal-phase patterns across brain regions.","whyItMatters":"Changes in endogenous opioid peptides during morphine use and withdrawal help explain tolerance, dependence, and the difficulty of quitting opioids. The nucleus accumbens changes are particularly relevant to addiction.","specificNumbers":"","methodology":"Male Sprague-Dawley rats received twice-daily morphine injections for 8 days. Opioid peptide levels were measured in multiple brain regions and pituitary by radioimmunoassay during treatment and withdrawal.","limitations":"Animal study in rats. Specific morphine dosing regimen may not represent all human opioid exposure patterns. Only measured peptide levels, not receptor changes."},{"rthcId":"RPEP-00338","title":"High-performance liquid chromatographic resolution of synthetic opiate and \"anti-opiate\" peptides from human plasma.","authors":"Partilla, J S; You, J; Rothman, R B","year":1995,"journal":"Journal of chromatography. B, Biomedical applications, 667(1), 49-56","doi":null,"pmid":"7663685","tags":["opioid-peptides","neuropeptides","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Single HPLC method achieved over 80% recovery of multiple opioid and anti-opioid peptides from human plasma in one analytical run.","whyItMatters":"Measuring both opioid and anti-opioid peptides simultaneously gives a complete picture of the opioid balance in patients. This is important for pain research, addiction studies, and understanding opioid drug effects.","specificNumbers":"","methodology":"Plasma samples diluted with trifluoroacetic acid, extracted on C18 cartridges, and analyzed by reversed-phase HPLC. Recovery and retention time consistency established for multiple peptide standards.","limitations":"Analytical method development using spiked samples. Sensitivity for measuring endogenous peptide levels in actual patient samples may vary. Method needs clinical validation."},{"rthcId":"RPEP-00339","title":"Design and biological activities of L-163,191 (MK-0677): a potent, orally active growth hormone secretagogue.","authors":"Patchett, A A; Nargund, R P; Tata, J R; Chen, M H; Barakat, K J; Johnston, D B; Cheng, K; Chan, W W; Butler, B; Hickey, G","year":1995,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 92(15), 7001-5","doi":null,"pmid":"7624358","tags":["mk-677","ghrp","hormone-optimization","peptide-design"],"studyType":"animal-study","evidenceStrength":"strong","keyFinding":"MK-0677 was characterized as the most potent orally active GH secretagogue, with EC50 of 1.3 nM in vitro, oral efficacy in dogs at 0.125 mg/kg, and confirmed anabolic effects in rodents.","whyItMatters":"MK-0677 became the most widely studied and used oral GH secretagogue. This paper established its potency, oral bioavailability, and anabolic potential, which are the properties that made it a game-changer in the field.","specificNumbers":"","methodology":"In vitro GH release from rat pituitary cells. Oral dosing studies in dogs measuring GH response. Repeated dosing for 4 days. Rodent anabolic efficacy studies with daily oral dosing.","limitations":"Animal study (rat cells, dogs, rodents). Clinical trials later revealed more nuanced effects in humans including increased appetite, blood sugar changes, and water retention."},{"rthcId":"RPEP-00340","title":"Effects of ethanolic extracts from Eschscholtzia californica and Corydalis cava on dimerization and oxidation of enkephalins.","authors":"Reimeier, C; Schneider, I; Schneider, W; Schäfer, H L; Elstner, E F","year":1995,"journal":"Arzneimittel-Forschung, 45(2), 132-6","doi":null,"pmid":"7710433","tags":["opioid-peptides","bioavailability","peptide-safety"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Eschscholtzia californica and Corydalis cava extracts inhibited peroxidase- and tyrosinase-mediated dimerization and oxidation of enkephalin peptides.","whyItMatters":"These plants have long traditions in herbal medicine for pain and anxiety. This study provides a potential biochemical mechanism: protecting natural opioid peptides from breakdown.","specificNumbers":"","methodology":"In vitro assays measuring enzymatic dimerization and oxidation of met-enkephalin and leu-enkephalin in the presence or absence of plant extracts. Alkaloid content of extracts characterized.","limitations":"In vitro study only. The plant extract concentrations tested may not be achievable in the body through oral consumption. Many other compounds in these extracts have their own effects."},{"rthcId":"RPEP-00341","title":"Potentiation of natriuretic peptides by neutral endopeptidase inhibitors.","authors":"Seymour, A A; Abboa-Offei, B E; Smith, P L; Mathers, P D; Asaad, M M; Rogers, W L","year":1995,"journal":"Clinical and experimental pharmacology & physiology, 22(1), 63-9","doi":null,"pmid":"7768036","tags":["natriuretic-peptides","cardiovascular","peptide-design"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"SQ 28603 potentiated both ANP effects in monkeys (increased plasma ANP, sodium excretion) and BNP effects in hypertensive rats (blood pressure lowering, renal responses).","whyItMatters":"NEP inhibitors protect the body's own blood pressure-lowering peptides from breakdown. This strategy became the basis for sacubitril/valsartan (Entresto), now a leading heart failure treatment.","specificNumbers":"","methodology":"Conscious monkeys received ANP infusion with or without SQ 28603. Conscious spontaneously hypertensive rats received BNP with or without NEP inhibitor. Measured plasma ANP, cGMP, sodium excretion, and blood pressure.","limitations":"Animal studies in monkeys and rats. Exogenous peptide infusion does not perfectly replicate endogenous natriuretic peptide physiology."},{"rthcId":"RPEP-00342","title":"Specific N- or C-terminus modified dynorphin and beta-endorphin peptides can selectively block excitatory opioid receptor functions in sensory neurons and unmask potent inhibitory effects of opioid agonists.","authors":"Shen, K F; Crain, S M","year":1995,"journal":"Brain research, 673(1), 30-8","doi":null,"pmid":"7757476","tags":["opioid-peptides","pain","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"N- or C-terminus modified dynorphin and beta-endorphin selectively blocked excitatory opioid receptor functions, dramatically enhancing the pain-relieving effects of opioid agonists.","whyItMatters":"If the excitatory opioid function can be selectively blocked, opioid pain relief could be greatly enhanced with lower doses, potentially reducing side effects and addiction risk.","specificNumbers":"","methodology":"Mouse dorsal root ganglion (DRG) sensory neurons in culture. Calcium-dependent action potential duration measured as an index of excitatory vs. inhibitory opioid effects. Modified peptides tested for selective blockade.","limitations":"In vitro study in cultured mouse sensory neurons. The bimodal opioid receptor concept is not universally accepted. Translation to whole-animal or human pain treatment is uncertain."},{"rthcId":"RPEP-00343","title":"Delta-sleep-inducing peptide does not affect CRH and meal-induced ACTH and cortisol secretion.","authors":"Späth-Schwalbe, E; Schäfer, A; Uthgenannt, D; Born, J; Fehm, H L","year":1995,"journal":"Psychoneuroendocrinology, 20(3), 231-7","doi":null,"pmid":"7777652","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00344","title":"Delta-sleep-inducing peptide sequels in the mechanisms of resistance to emotional stress.","authors":"Sudakov, K V; Coghlan, J P; Kotov, A V; Salieva, R M; Polyntsev YuV; Koplik, E V","year":1995,"journal":"Annals of the New York Academy of Sciences, 771, 240-51","doi":null,"pmid":"8597403","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"DSIP administration produced marked changes in substance P, beta-endorphin, and corticosterone levels in both the hypothalamus and blood plasma. These changes persisted at both 1 hour and 24 hours after injection, indicating a prolonged cascade of molecular effects. The response pattern differed between Wistar rats and August rats — two strains with different baseline resistance to emotional stress. DSIP stimulated stress-resistance mechanisms more strongly in Wistar rats than in August rats, which are already more stress-resistant.","whyItMatters":"DSIP is one of the more mysterious neuropeptides — discovered decades ago but still not fully understood. This study suggests it doesn't simply induce sleep but triggers a long-lasting reprogramming of the neuroendocrine stress response. Understanding how a single peptide injection can produce changes lasting 24+ hours could have implications for stress resilience, PTSD research, and neuropeptide-based therapeutics.","specificNumbers":"","methodology":"Male Wistar and August rats were divided into 6 groups: controls, stressed animals, and four DSIP-treated groups with varying timing of injection relative to stress and decapitation. Stress was induced by restraining rats by their tails for 12 hours per night over 5 consecutive days. Substance P and beta-endorphin were measured radioimmunologically in hypothalamus and plasma. Blood corticosterone was also measured radioimmunologically.","limitations":"This is an animal study from 1995 with a relatively harsh stress model (tail restraint). Sample sizes per group were not specified in the abstract. The study measured peptide and hormone levels but did not assess behavioral outcomes like sleep quality or anxiety. Radioimmunological assays of that era were less precise than modern methods. Results in rats may not directly translate to human stress physiology."},{"rthcId":"RPEP-00345","title":"Opioids and sexual behavior of male rats: involvement of the medial preoptic area.","authors":"van Furth, W R; van Emst, M G; van Ree, J M","year":1995,"journal":"Behavioral neuroscience, 109(1), 123-34","doi":null,"pmid":"7734068","tags":["opioid-peptides","sexual-health","neuropeptides"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Beta-endorphin in the MPOA dose-dependently impaired male rat sexual behavior, prevented by naloxone, while other opioid peptides were less effective at equivalent doses.","whyItMatters":"Opioid drugs commonly cause sexual dysfunction. This study identifies the specific brain region and the specific opioid peptide (beta-endorphin) most responsible for suppressing male sexual function.","specificNumbers":"","methodology":"Sexually experienced male rats received local MPOA infusions of beta-endorphin, alpha-endorphin, dynorphin A, or met-enkephalin. Sexual behavior parameters were measured during standard mating tests. Naloxone was tested as a blocker.","limitations":"Animal study in rats with direct brain injection. Sexual behavior in rats does not directly model human sexual function. Only male rats were studied."},{"rthcId":"RPEP-00346","title":"Phorbol ester regulation of opioid peptide gene expression in myocardial cells. Role of nuclear protein kinase.","authors":"Ventura, C; Pintus, G; Vaona, I; Bennardini, F; Pinna, G; Tadolini, B","year":1995,"journal":"The Journal of biological chemistry, 270(50), 30115-20","doi":null,"pmid":"8530417","tags":["opioid-peptides","cardiovascular","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Phorbol ester induced a concentration- and time-dependent increase in prodynorphin mRNA in cardiac myocytes, peaking at 4 hours and mediated through protein kinase C.","whyItMatters":"The discovery that the heart produces its own opioid peptides suggests a local cardioprotective system that may help the heart cope with stress, ischemia, or injury.","specificNumbers":"","methodology":"Adult rat ventricular cardiac myocytes were cultured with or without phorbol ester. Prodynorphin mRNA levels were measured over time and at varying concentrations, with protein kinase C inhibitors used to confirm the signaling pathway.","limitations":"In vitro study using isolated rat heart cells stimulated with a pharmacological agent. The physiological conditions that would naturally trigger this response in the intact heart were not established."},{"rthcId":"RPEP-00347","title":"Development of a lipopeptide-based therapeutic vaccine to treat chronic HBV infection. I. Induction of a primary cytotoxic T lymphocyte response in humans.","authors":"Vitiello, A; Ishioka, G; Grey, H M; Rose, R; Farness, P; LaFond, R; Yuan, L; Chisari, F V; Furze, J; Bartholomeuz, R","year":1995,"journal":"The Journal of clinical investigation, 95(1), 341-9","doi":null,"pmid":"7814635","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00348","title":"Degradation of IGF-I in the adult rat gastrointestinal tract is limited by a specific antiserum or the dietary protein casein.","authors":"Xian, C J; Shoubridge, C A; Read, L C","year":1995,"journal":"The Journal of endocrinology, 146(2), 215-25","doi":null,"pmid":"7561632","tags":["gut-healing","hormone-optimization","bioavailability"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"IGF-1 had a half-life of only 2 minutes in the duodenum and ileum, but casein protein significantly protected it from degradation in the gut.","whyItMatters":"This study addresses one of the biggest challenges in peptide therapeutics — oral bioavailability — and identified casein as a practical protective agent for gut-delivered peptides.","specificNumbers":"","methodology":"Researchers injected radiolabeled IGF-1 into ligated gut segments of fasted adult rats and measured its survival using three different assays (TCA precipitation, antibody binding, and receptor binding).","limitations":"Animal study using ligated gut segments, which don't fully represent normal gut transit. The 8.6 ng dose is much smaller than therapeutic doses. Protection by casein may vary with different peptides."},{"rthcId":"RPEP-00349","title":"Brain and plasma levels of opioid peptides are altered in rats with thioacetamide-induced fulminant hepatic failure: implications for the treatment of hepatic encephalopathy with opioid antagonists.","authors":"Yurdaydin, C; Li, Y; Ha, J H; Jones, E A; Rothman, R; Basile, A S","year":1995,"journal":"The Journal of pharmacology and experimental therapeutics, 273(1), 185-92","doi":null,"pmid":"7714765","tags":["opioid-peptides","liver","neuroprotection"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Fulminant hepatic failure significantly altered Met-enkephalin, Leu-enkephalin, dynorphin A, and beta-endorphin levels in multiple brain regions and plasma.","whyItMatters":"This study provided direct evidence that liver failure disrupts the brain's opioid peptide system, helping explain the neurological symptoms of hepatic encephalopathy and justifying opioid antagonist treatment.","specificNumbers":"","methodology":"Rats were given thioacetamide to induce fulminant hepatic failure. Opioid peptide levels were measured in discrete brain regions and plasma using radioimmunoassay and compared to healthy controls.","limitations":"Animal study using chemically induced liver failure, which may not perfectly replicate human hepatic encephalopathy. The causal relationship between altered opioid levels and neurological symptoms was not directly established."},{"rthcId":"RPEP-00350","title":"Age-related mu-, delta-and kappa-opioid ligands in respiratory-related brain regions of piglets: effect of prenatal cocaine.","authors":"Zhang, C; Moss, I R","year":1995,"journal":"Brain research. Developmental brain research, 87(2), 188-93","doi":null,"pmid":"7586501","tags":["opioid-peptides","respiratory","neuropeptides"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Opioid peptide levels in respiratory brainstem regions change significantly between young and older piglets, and prenatal cocaine exposure disrupts this developmental pattern.","whyItMatters":"Understanding how endogenous opioid peptides affect neonatal breathing control helps explain why newborns are vulnerable to apnea and why prenatal drug exposure increases this risk.","specificNumbers":"","methodology":"Piglets (young: 2-5 days, older: 18+ days) with and without prenatal cocaine exposure had respiratory-related brainstem regions dissected and analyzed for mu, delta, and kappa opioid receptor ligands.","limitations":"Animal study using piglets, which may differ from human neonatal physiology. Prenatal cocaine exposure model may not perfectly replicate human exposure patterns."},{"rthcId":"RPEP-00351","title":"Identification of dynorphins as endogenous ligands for an opioid receptor-like orphan receptor.","authors":"Zhang, S; Yu, L","year":1995,"journal":"The Journal of biological chemistry, 270(39), 22772-6","doi":null,"pmid":"7559404","tags":["opioid-peptides","receptor-signaling","neuropeptides"],"studyType":"in-vitro","evidenceStrength":"strong","keyFinding":"Dynorphin peptides activate a cloned orphan receptor with high sequence homology to opioid receptors, functioning as its endogenous ligands via G protein-coupled potassium channel activation.","whyItMatters":"Identifying dynorphin as the ligand for this orphan receptor revealed a fourth branch of the opioid receptor system, opening new avenues for pain, addiction, and mood disorder research.","specificNumbers":"","methodology":"The orphan receptor was expressed in Xenopus oocytes and mammalian cell lines (CHO-K1, HEK-293). Receptor activation was measured by G protein-activated potassium channel coupling in oocytes and dose-response curves were generated.","limitations":"In vitro study using heterologous expression systems. The physiological role of this receptor-ligand interaction in the intact organism was not established in this study."},{"rthcId":"RPEP-00352","title":"Protein kinase C-dependent growth hormone releasing peptides stimulate cyclic adenosine 3',5'-monophosphate production by human pituitary somatotropinomas expressing gsp oncogenes: evidence for crosstalk between transduction pathways.","authors":"Adams, E F; Lei, T; Buchfelder, M; Bowers, C Y; Fahlbusch, R","year":1996,"journal":"Molecular endocrinology (Baltimore, Md.), 10(4), 432-8","doi":null,"pmid":"8721987","tags":["ghrp","cancer","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"GHRP-2 was considerably more potent than GHRP-6 at stimulating GH release through PKC-dependent pathways, and both caused crosstalk with the cAMP pathway in gsp oncogene-expressing tumors.","whyItMatters":"Understanding how GHRPs work at the cellular signaling level helps optimize their clinical use and explains why GHRP-2 may be more effective than GHRP-6.","specificNumbers":"","methodology":"Human pituitary somatotropinomas (with and without gsp oncogenes) were cultured and treated with GHRP-2 and GHRP-6. Phosphatidylinositol hydrolysis, cAMP production, and GH secretion were measured. PKC inhibition was used to confirm the signaling pathway.","limitations":"Study used human pituitary tumor cells, not normal pituitary tissue. Tumor cells may respond differently than healthy cells. In vitro conditions don't replicate in vivo complexity."},{"rthcId":"RPEP-00353","title":"Growth hormone-releasing peptides: clinical and basic aspects.","authors":"Argente, J; García-Segura, L M; Pozo, J; Chowen, J A","year":1996,"journal":"Hormone research, 46(4-5), 155-9","doi":null,"pmid":"8950613","tags":["ghrp","hormone-optimization","clinical-trials"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"GHRPs stimulate growth hormone release through a receptor distinct from GHRH, acting at both the pituitary and hypothalamic level, with consistent effects demonstrated across species and administration routes.","whyItMatters":"Understanding GHRPs' distinct mechanism opened the door to combination therapies with GHRH and led to the discovery of the ghrelin receptor, transforming growth hormone research.","specificNumbers":"","methodology":"Comprehensive literature review covering in vivo and in vitro studies of GHRPs in animals and humans, examining mechanisms, dose-response relationships, and clinical applications.","limitations":"As a review article from 1996, it predates the discovery of ghrelin and the full characterization of the GHS receptor. Some conclusions may have been refined by subsequent research."},{"rthcId":"RPEP-00354","title":"Neurobiology of corticotropin releasing factor (CRF) receptors and CRF-binding protein: implications for the treatment of CNS disorders.","authors":"Behan, D P; Grigoriadis, D E; Lovenberg, T; Chalmers, D; Heinrichs, S; Liaw, C; De Souza, E B","year":1996,"journal":"Molecular psychiatry, 1(4), 265-77","doi":null,"pmid":"9118350","tags":["neuropeptides","anxiety-mood","receptor-signaling"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Three CRF receptor subtypes (CRF1, CRF2alpha, CRF2beta) and a CRF-binding protein coordinate stress responses, and newly developed non-peptide CRF antagonists show therapeutic promise.","whyItMatters":"CRF is the master regulator of the body's stress response. Understanding its receptor subtypes and developing targeted antagonists could lead to fundamentally new treatments for anxiety and depression.","specificNumbers":"","methodology":"Review of molecular biology, pharmacology, and neuroscience literature on CRF receptors, CRF-binding protein, and early CRF antagonist drug development.","limitations":"Review article from 1996; CRF antagonist drug development was still in early stages. Some therapeutic predictions may not have been borne out in subsequent clinical trials."},{"rthcId":"RPEP-00355","title":"Opiate receptor-mediated mechanisms in the regulation of cerebral blood flow.","authors":"Benyó, Z; Wahl, M","year":1996,"journal":"Cerebrovascular and brain metabolism reviews, 8(4), 326-57","doi":null,"pmid":"8969868","tags":["opioid-peptides","cardiovascular","neuroprotection"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Endogenous opioid peptides in cerebral perivascular nerves and CSF actively regulate cerebral blood flow through opiate receptors, with concentrations changing in response to perfusion pressure and oxygen tension.","whyItMatters":"Understanding how opioid peptides regulate brain blood flow could lead to new neuroprotective strategies for stroke, traumatic brain injury, and other conditions involving cerebral blood flow compromise.","specificNumbers":"","methodology":"Literature review synthesizing evidence on opioid peptide distribution in cerebral vasculature, receptor expression, and functional studies of opioid-mediated cerebral blood flow regulation.","limitations":"Review article synthesizing primarily animal research. Direct human evidence for opioid-mediated cerebral blood flow regulation was limited at time of publication."},{"rthcId":"RPEP-00356","title":"Gastrointestinal peptide hormones in acute viral hepatitis.","authors":"Budillon, G; Cuomo, R; Taccone, W; Panico, G; Pumpo, R; Iaquinto, G; Manzillo, G","year":1996,"journal":"The Italian journal of gastroenterology, 28(2), 86-90","doi":null,"pmid":"8782000","tags":["neuropeptides","liver","gut-healing"],"studyType":"cross-sectional","evidenceStrength":"preliminary","keyFinding":"Multiple gastrointestinal peptide hormone levels were significantly altered during acute hepatic cytonecrosis and returned toward normal during liver regeneration.","whyItMatters":"This study reveals the liver's role as a key regulator of gut peptide hormones, explaining why liver disease causes digestive symptoms and suggesting peptide hormone monitoring could track liver recovery.","specificNumbers":"","methodology":"Cross-sectional study measuring plasma gastrointestinal peptide hormone concentrations in 10 patients with acute viral hepatitis (8 hepatitis A, 2 hepatitis B) during acute illness and recovery.","limitations":"Small sample size (10 patients). Mixed hepatitis types (A and B). Cross-sectional design limits causal inference. Specific peptide hormones measured not detailed in abstract."},{"rthcId":"RPEP-00357","title":"Stimulation of the growth hormone (GH)-insulin-like growth factor I axis by daily oral administration of a GH secretogogue (MK-677) in healthy elderly subjects.","authors":"Chapman, I M; Bach, M A; Van Cauter, E; Farmer, M; Krupa, D; Taylor, A M; Schilling, L M; Cole, K Y; Skiles, E H; Pezzoli, S S; Hartman, M L; Veldhuis, J D; Gormley, G J; Thorner, M O","year":1996,"journal":"The Journal of clinical endocrinology and metabolism, 81(12), 4249-57","doi":null,"pmid":"8954023","tags":["mk-677","hormone-optimization","anti-aging","clinical-trials"],"studyType":"RCT","evidenceStrength":"strong","keyFinding":"Daily oral MK-677 significantly stimulated the GH-IGF-1 axis in healthy elderly adults aged 64-81, raising levels toward those seen in younger individuals.","whyItMatters":"Declining growth hormone is associated with aging-related muscle loss, fat gain, and cardiovascular risk. An oral compound that safely restores youthful GH levels could have significant anti-aging applications.","specificNumbers":"","methodology":"Randomized controlled trial with 32 healthy elderly subjects (15 women, 17 men, aged 64-81). Participants received oral MK-677 daily, and GH and IGF-1 levels were measured.","limitations":"Relatively small sample size. Short-term study; long-term effects and safety not established. Functional outcomes (muscle mass, strength, body composition) were not the primary endpoints."},{"rthcId":"RPEP-00358","title":"Effects of a 7-day treatment with a novel, orally active, growth hormone (GH) secretagogue, MK-677, on 24-hour GH profiles, insulin-like growth factor I, and adrenocortical function in normal young men.","authors":"Copinschi, G; Van Onderbergen, A; L'Hermite-Balériaux, M; Mendel, C M; Caufriez, A; Leproult, R; Bolognese, J A; De Smet, M; Thorner, M O; Van Cauter, E","year":1996,"journal":"The Journal of clinical endocrinology and metabolism, 81(8), 2776-82","doi":null,"pmid":"8768828","tags":["mk-677","hormone-optimization","clinical-trials"],"studyType":"RCT","evidenceStrength":"strong","keyFinding":"Bedtime MK-677 at 25 mg for 7 days significantly increased 24-hour GH profiles and IGF-1 in young men without altering adrenocortical function.","whyItMatters":"This study established a practical dosing protocol (25 mg at bedtime) for MK-677 and confirmed it works in young men without disrupting the cortisol axis — a key safety consideration.","specificNumbers":"","methodology":"Randomized, double-blind, three-period crossover study. 9 healthy young men received placebo, 5 mg, or 25 mg MK-677 orally at bedtime for 7 consecutive days per period. 24-hour GH profiles, IGF-1, and cortisol were measured.","limitations":"Very small sample (9 men). Only 7-day treatment period. No women included. Limited to hormonal endpoints without functional outcome measures."},{"rthcId":"RPEP-00359","title":"Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study.","authors":"Dorr, R T; Lines, R; Levine, N; Brooks, C; Xiang, L; Hruby, V J; Hadley, M E","year":1996,"journal":"Life sciences, 58(20), 1777-84","doi":null,"pmid":"8637402","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00360","title":"Susceptibilities of Bordetella pertussis strains to antimicrobial peptides.","authors":"Fernandez, R C; Weiss, A A","year":1996,"journal":"Antimicrobial agents and chemotherapy, 40(4), 1041-3","doi":null,"pmid":"8849226","tags":["antimicrobial-peptides","infection","immune-function"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Cecropin B was the most potent antimicrobial peptide against B. pertussis, with cecropins generally outperforming magainins, defensins, and protamine.","whyItMatters":"Whooping cough remains a significant public health concern. Identifying effective antimicrobial peptides against B. pertussis could lead to novel treatment approaches, especially as antibiotic resistance grows.","specificNumbers":"","methodology":"In vitro susceptibility testing of B. pertussis strains against multiple antimicrobial peptides, determining the concentration required to inhibit or kill 50% of the bacterial population (MIC50/MBC50).","limitations":"In vitro study only. Effectiveness in a test tube doesn't guarantee clinical efficacy. Bioavailability, toxicity, and stability of these peptides in the human body were not assessed."},{"rthcId":"RPEP-00361","title":"Natriuretic peptides and cyclic guanosine 3',5'-monophosphate in asymptomatic and symptomatic left ventricular dysfunction.","authors":"Friedl, W; Mair, J; Thomas, S; Pichler, M; Puschendorf, B","year":1996,"journal":"Heart (British Cardiac Society), 76(2), 129-36","doi":null,"pmid":"8795474","tags":["natriuretic-peptides","cardiovascular","clinical-trials"],"studyType":"cross-sectional","evidenceStrength":"strong","keyFinding":"ANP, BNP, and cGMP were compared as screening markers for asymptomatic and symptomatic left ventricular dysfunction, with potential utility for early detection.","whyItMatters":"Detecting heart dysfunction before symptoms appear allows earlier treatment that can prevent heart failure progression. Simple blood markers like BNP could enable population-wide screening.","specificNumbers":"","methodology":"Cross-sectional study directly comparing plasma ANP, BNP, and cGMP levels in patients with asymptomatic versus symptomatic left ventricular dysfunction to evaluate their screening potential.","limitations":"Cross-sectional design limits ability to determine predictive value over time. Abstract doesn't detail sensitivity/specificity values or sample sizes."},{"rthcId":"RPEP-00362","title":"PhoP-PhoQ activates transcription of pmrAB, encoding a two-component regulatory system involved in Salmonella typhimurium antimicrobial peptide resistance.","authors":"Gunn, J S; Miller, S I","year":1996,"journal":"Journal of bacteriology, 178(23), 6857-64","doi":null,"pmid":"8955307","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00363","title":"The effects of magainin 2, cecropin, mastoparan and melittin on Brucella abortus.","authors":"Halling, S M","year":1996,"journal":"Veterinary microbiology, 51(1-2), 187-92","doi":null,"pmid":"8828135","tags":["antimicrobial-peptides","infection","immune-function"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Antimicrobial peptide effectiveness against Brucella abortus depended significantly on bacterial surface structure, with rough mutants showing different susceptibility patterns than smooth strains.","whyItMatters":"Brucellosis remains a significant zoonotic disease worldwide. Understanding which antimicrobial peptides work against it and why could lead to new treatment options.","specificNumbers":"","methodology":"In vitro viability testing of four antimicrobial peptides against multiple B. abortus strains (wild type, vaccine strains, rough mutants) and Salmonella typhimurium as a control.","limitations":"In vitro study only. Clinical applicability of these peptides against Brucella infections was not assessed. Peptide stability and toxicity in vivo unknown."},{"rthcId":"RPEP-00364","title":"Increased circulating adrenomedullin, a novel vasodilatory peptide, in sepsis.","authors":"Hirata, Y; Mitaka, C; Sato, K; Nagura, T; Tsunoda, Y; Amaha, K; Marumo, F","year":1996,"journal":"The Journal of clinical endocrinology and metabolism, 81(4), 1449-53","doi":null,"pmid":"8636349","tags":["neuropeptides","cardiovascular","infection"],"studyType":"cross-sectional","evidenceStrength":"moderate","keyFinding":"Plasma adrenomedullin concentrations were extremely elevated in septic ICU patients compared to healthy controls, correlating with disease severity.","whyItMatters":"Understanding which peptides drive the fatal blood pressure collapse in sepsis could lead to targeted treatments. Adrenomedullin's vasodilatory properties make it a key suspect in sepsis pathophysiology.","specificNumbers":"","methodology":"Cross-sectional study measuring plasma immunoreactive adrenomedullin levels in 12 septic patients upon ICU admission, compared to healthy controls.","limitations":"Small sample (12 patients). Cross-sectional design cannot determine whether adrenomedullin elevation is a cause or consequence of sepsis. Correlation with severity doesn't prove causation."},{"rthcId":"RPEP-00365","title":"Transdermal delivery of peptides by iontophoresis.","authors":"Hirvonen, J; Kalia, Y N; Guy, R H","year":1996,"journal":"Nature biotechnology, 14(13), 1710-3","doi":null,"pmid":"9634857","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00366","title":"Activation of mu-opioid receptors are required for the conditioned enhancement of NK cell activity.","authors":"Hsueh, C M; Chen, S F; Huang, H J; Ghanta, V K; Hiramoto, R N","year":1996,"journal":"Brain research, 737(1-2), 263-8","doi":null,"pmid":"8930374","tags":["opioid-peptides","immune-function","cancer"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Conditioned enhancement of NK cell activity depends on mu-opioid receptor activation, with beta-endorphin and met-enkephalin as the key mediating peptides.","whyItMatters":"This study reveals that the immune system can be 'trained' through opioid peptide signaling, and identifies the specific receptor (mu) responsible — a finding with implications for immune-enhancing therapies.","specificNumbers":"","methodology":"Animal study using selective opioid receptor antagonists to determine which receptor type mediates the conditioned enhancement of natural killer cell activity in rats.","limitations":"Animal study using pharmacological receptor blockade. The conditioning paradigm may not directly apply to human immune training. Specificity of receptor antagonists is not absolute."},{"rthcId":"RPEP-00367","title":"Chronic intracerebroventricular administration of beta-endorphin augments natural killer cell cytotoxicity in rats.","authors":"Jonsdottir, I H; Johansson, C; Asea, A; Hellstrand, K; Thorén, P; Hoffmann, P","year":1996,"journal":"Regulatory peptides, 62(2-3), 113-8","doi":null,"pmid":"8795073","tags":["opioid-peptides","immune-function","cancer"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Chronic intracerebroventricular beta-endorphin infusion significantly enhanced in vivo NK cell cytotoxicity and altered splenic and peripheral blood lymphocyte phenotypes.","whyItMatters":"This demonstrates that the brain's opioid peptide system directly controls cancer-fighting immune cells, providing a biological mechanism for how mental state and stress affect cancer surveillance.","specificNumbers":"","methodology":"Spontaneously hypertensive rats received chronic intracerebroventricular infusions of opioid peptides. In vivo NK cell activity was measured by clearance of radiolabeled tumor cells from lung tissue. Lymphocyte phenotyping was performed on spleen and blood.","limitations":"Used direct brain infusion — not a practical administration route. Spontaneously hypertensive rats may respond differently than healthy animals. The immune-enhancing effect may not translate to other species."},{"rthcId":"RPEP-00368","title":"The growth hormone-releasing peptide KP-102 induces c-fos expression in the arcuate nucleus.","authors":"Kamegai, J; Hasegawa, O; Minami, S; Sugihara, H; Wakabayashi, I","year":1996,"journal":"Brain research. Molecular brain research, 39(1-2), 153-9","doi":null,"pmid":"8804723","tags":["ghrp","hormone-optimization","neuropeptides"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"KP-102 induces c-fos expression specifically in the arcuate nucleus, and this occurs even in hypophysectomized rats, confirming a direct hypothalamic site of action.","whyItMatters":"Proving GHRPs act directly on the hypothalamus (not just the pituitary) revealed a dual mechanism of action, explaining their potent GH-releasing effects and supporting combination therapy with GHRH.","specificNumbers":"","methodology":"Rat brains were processed for in situ hybridization of c-fos mRNA after systemic KP-102 administration. Both intact and hypophysectomized (pituitary-removed) adult male Wistar rats were tested.","limitations":"Animal study with a specific GHRP variant (KP-102). The c-fos marker shows activation but doesn't reveal the functional consequence. Hypophysectomy creates an artificial state."},{"rthcId":"RPEP-00369","title":"Greater efficacy of episodic than continuous growth hormone-releasing hormone (GHRH) administration in promoting slow-wave sleep (SWS).","authors":"Marshall, L; Mölle, M; Böschen, G; Steiger, A; Fehm, H L; Born, J","year":1996,"journal":"The Journal of clinical endocrinology and metabolism, 81(3), 1009-13","doi":null,"pmid":"8772566","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00370","title":"The effect of repeated administration of hexarelin, a growth hormone releasing peptide, and growth hormone releasing hormone on growth hormone responsivity.","authors":"Massoud, A F; Hindmarsh, P C; Matthews, D R; Brook, C G","year":1996,"journal":"Clinical endocrinology, 44(5), 555-62","doi":null,"pmid":"8762732","tags":["ghrp","hormone-optimization","clinical-trials"],"studyType":"RCT","evidenceStrength":"strong","keyFinding":"Hexarelin maintained GH-releasing efficacy with repeated administration, and hexarelin plus GHRH produced a synergistic GH response exceeding individual effects.","whyItMatters":"Tolerance is a major concern with repeated peptide use. Demonstrating that hexarelin maintains its effect with repeat dosing supports its viability as a clinical GH secretagogue.","specificNumbers":"","methodology":"Randomized, double-blind, crossover RCT with single IV boluses of hexarelin, GHRH, or hexarelin+GHRH administered as two sequential doses to assess responsivity maintenance.","limitations":"Short-term study assessing only acute repeated doses. Long-term tolerance with daily chronic use was not assessed. Sample size and specific participant numbers not detailed in abstract."},{"rthcId":"RPEP-00371","title":"An antimicrobial peptide, magainin 2, induced rapid flip-flop of phospholipids coupled with pore formation and peptide translocation.","authors":"Matsuzaki, K; Murase, O; Fujii, N; Miyajima, K","year":1996,"journal":"Biochemistry, 35(35), 11361-8","doi":null,"pmid":"8784191","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00372","title":"The therapeutic potential of neuropeptide Y. Analgesic, anxiolytic and antihypertensive.","authors":"Munglani, R; Hudspith, M J; Hunt, S P","year":1996,"journal":"Drugs, 52(3), 371-89","doi":null,"pmid":"8875128","tags":["neuropeptides","pain","anxiety-mood","cardiovascular"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"NPY mediates analgesia and hyperalgesia through distinct receptor subtypes, alongside established roles in blood pressure regulation and anxiety modulation.","whyItMatters":"NPY receptors could provide new drug targets for pain, anxiety, and hypertension that work through fundamentally different mechanisms than current medications.","specificNumbers":"","methodology":"Literature review synthesizing evidence on NPY's analgesic, anxiolytic, and antihypertensive effects across receptor subtypes.","limitations":"Review article; most evidence from animal studies. NPY-based therapeutics face delivery challenges as the peptide doesn't easily cross the blood-brain barrier."},{"rthcId":"RPEP-00373","title":"Intracerebroventricular orphanin FQ/nociceptin suppresses dopamine release in the nucleus accumbens of anaesthetized rats.","authors":"Murphy, N P; Ly, H T; Maidment, N T","year":1996,"journal":"Neuroscience, 75(1), 1-4","doi":null,"pmid":"8923516","tags":["neuropeptides","addiction","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Orphanin FQ/nociceptin suppressed dopamine release in the nucleus accumbens, acting opposite to classical opioids which typically increase dopamine in this reward-related region.","whyItMatters":"Discovering a natural anti-reward peptide provides new understanding of how the brain balances pleasure and motivation, with direct relevance to addiction and depression research.","specificNumbers":"","methodology":"Intracerebroventricular injection of orphanin FQ/nociceptin in anesthetized rats with in vivo measurement of dopamine release in the nucleus accumbens.","limitations":"Animal study under anesthesia, which may alter dopamine dynamics. Direct brain injection is not a physiological route. Single brain region measured."},{"rthcId":"RPEP-00374","title":"Opioid receptor agonists activate pertussis toxin-sensitive G proteins and inhibit adenylyl cyclase in canine cardiac sarcolemma.","authors":"Niroomand, F; Mura, R A; Piacentini, L; Kübler, W","year":1996,"journal":"Naunyn-Schmiedeberg's archives of pharmacology, 354(5), 643-9","doi":null,"pmid":"8938664","tags":["opioid-peptides","cardiovascular","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Mu, delta, and kappa opioid receptors in cardiac sarcolemma activate pertussis toxin-sensitive G proteins and inhibit adenylyl cyclase, confirming a complete opioid signaling pathway in the heart.","whyItMatters":"Confirming functional opioid receptors and their signaling pathways in the heart opens the door to understanding how opioid peptides protect cardiac tissue during stress and ischemia.","specificNumbers":"","methodology":"Highly purified canine cardiac sarcolemmal membranes were analyzed for opioid receptor binding, G protein activation (GTPase), and adenylyl cyclase inhibition using selective agonists for each receptor type.","limitations":"In vitro study using isolated canine cardiac membranes. The functional consequences of this signaling in intact hearts were not assessed."},{"rthcId":"RPEP-00375","title":"Plasma brain natriuretic peptide as an indicator of left ventricular systolic function and long-term survival after acute myocardial infarction. Comparison with plasma atrial natriuretic peptide and N-terminal proatrial natriuretic peptide.","authors":"Omland, T; Aakvaag, A; Bonarjee, V V; Caidahl, K; Lie, R T; Nilsen, D W; Sundsfjord, J A; Dickstein, K","year":1996,"journal":"Circulation, 93(11), 1963-9","doi":null,"pmid":"8640969","tags":["natriuretic-peptides","cardiovascular","clinical-trials"],"studyType":"cohort","evidenceStrength":"strong","keyFinding":"Plasma BNP may increase proportionally more than ANP after acute myocardial infarction and chronic heart failure, potentially offering superior diagnostic and prognostic value.","whyItMatters":"Identifying the best blood biomarker for heart function after a heart attack helps clinicians make better treatment decisions and predict which patients are at highest risk.","specificNumbers":"","methodology":"Cohort study comparing plasma BNP, ANP, and N-terminal proANP as indicators of left ventricular systolic function and predictors of long-term survival in patients after acute myocardial infarction.","limitations":"Cohort study design; details of sample size and follow-up duration not specified in abstract. Comparison methodology may vary from modern assay standards."},{"rthcId":"RPEP-00376","title":"A class of highly potent antibacterial peptides derived from pardaxin, a pore-forming peptide isolated from Moses sole fish Pardachirus marmoratus.","authors":"Oren, Z; Shai, Y","year":1996,"journal":"European journal of biochemistry, 237(1), 303-10","doi":null,"pmid":"8620888","tags":["antimicrobial-peptides","venom-peptides","peptide-design"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Pardaxin possesses high antibacterial activity, and engineered variants achieved potent bacterial killing while reducing harmful effects on mammalian cells.","whyItMatters":"Engineering selective antibacterial peptides from natural toxins provides a template for developing new antibiotics that kill bacteria without harming human cells — critical as antibiotic resistance grows.","specificNumbers":"","methodology":"In vitro testing of pardaxin and engineered derivatives for antibacterial activity against various strains and cytotoxicity against mammalian cells.","limitations":"In vitro study only. Engineered peptides need in vivo testing for stability, bioavailability, and safety before clinical development."},{"rthcId":"RPEP-00377","title":"Opioid peptide participates in post-tetanic twitch inhibition in guinea pig isolated ileum.","authors":"Ozaki, M; Masuda, Y; Yamamoto, H","year":1996,"journal":"Journal of the autonomic nervous system, 58(3), 147-52","doi":null,"pmid":"8738307","tags":["opioid-peptides","gut-healing","bioavailability"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Endogenous opioid peptides contribute to post-tetanic inhibition of gut muscle contractions, and peptidase inhibitors enhance this effect by protecting naturally released peptides from degradation.","whyItMatters":"Understanding how the gut's own opioid peptides regulate motility helps explain normal digestive function and the gut effects of opioid drugs.","specificNumbers":"","methodology":"In vitro experiments using isolated guinea pig ileum with electrical field stimulation. Met-enkephalin, dynorphin, and beta-endorphin were tested with and without peptidase inhibitors (amastatin, phosphoramidon, captopril).","limitations":"In vitro study using isolated tissue. Conditions may not reflect intact gut physiology. Guinea pig tissue may differ from human intestine."},{"rthcId":"RPEP-00378","title":"Organ targeting in vivo using phage display peptide libraries.","authors":"Pasqualini, R; Ruoslahti, E","year":1996,"journal":"Nature, 380(6572), 364-6","doi":null,"pmid":"8598934","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00379","title":"Solubilization and characterization of a growth hormone secretagogue receptor from porcine anterior pituitary membranes.","authors":"Pomés, A; Pong, S S; Schaeffer, J M","year":1996,"journal":"Biochemical and biophysical research communications, 225(3), 939-45","doi":null,"pmid":"8780714","tags":["ghrp","mk-677","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"The GH secretagogue receptor was solubilized as a ~255 kDa receptor-ligand-G-protein complex from porcine pituitary, confirming it is distinct from the GHRH receptor.","whyItMatters":"Isolating the GH secretagogue receptor was essential for understanding how GHRPs and MK-677 work and for the eventual cloning of the ghrelin receptor (GHS-R).","specificNumbers":"","methodology":"Porcine anterior pituitary membranes were solubilized with digitonin detergent, and the GH secretagogue receptor complex was characterized by size and binding properties.","limitations":"In vitro biochemistry using solubilized membranes. Molecular mass estimate may include detergent-associated artifacts. Porcine receptor may differ from human."},{"rthcId":"RPEP-00380","title":"Identification of a new G-protein-linked receptor for growth hormone secretagogues.","authors":"Pong, S S; Chaung, L Y; Dean, D C; Nargund, R P; Patchett, A A; Smith, R G","year":1996,"journal":"Molecular endocrinology (Baltimore, Md.), 10(1), 57-61","doi":null,"pmid":"8838145","tags":["ghrp","mk-677","receptor-signaling","peptide-design"],"studyType":"in-vitro","evidenceStrength":"strong","keyFinding":"A specific high-affinity G-protein-linked receptor for GH secretagogues was identified, operating through a distinct signaling pathway from GHRH.","whyItMatters":"Identifying this receptor was a landmark discovery that explained how GH secretagogues work and led directly to the discovery of ghrelin — the body's natural hunger hormone.","specificNumbers":"","methodology":"Molecular biology approach using receptor binding assays, G-protein coupling analysis, and signaling pathway characterization to identify and characterize the GHS receptor.","limitations":"Initial characterization study. The receptor's natural ligand was not yet identified. Full tissue distribution and physiological role remained to be determined."},{"rthcId":"RPEP-00381","title":"Combination thymosin alpha 1 and lymphoblastoid interferon treatment in chronic hepatitis C.","authors":"Rasi, G; DiVirgilio, D; Mutchnick, M G; Colella, F; Sinibaldi-Vallebona, P; Pierimarchi, P; Valli, B; Garaci, E","year":1996,"journal":"Gut, 39(5), 679-83","doi":null,"pmid":"9026482","tags":["thymosin-alpha-1","immune-function","infection","clinical-trials"],"studyType":"RCT","evidenceStrength":"moderate","keyFinding":"Combination thymosin alpha-1 (1 mg twice weekly) and lymphoblastoid interferon was tested as a strategy to improve sustained response rates in chronic hepatitis C over interferon monotherapy.","whyItMatters":"Before direct-acting antivirals, hepatitis C treatment had very low cure rates. Thymosin alpha-1 combination therapy represented an attempt to boost immune-mediated viral clearance.","specificNumbers":"","methodology":"Randomized clinical trial assessing one year of combination thymosin alpha-1 and lymphoblastoid interferon treatment in patients with chronic hepatitis C.","limitations":"Abstract doesn't detail response rates, sample size, or comparative arm design. Pre-direct-acting-antiviral era study may have limited current clinical relevance for HCV specifically."},{"rthcId":"RPEP-00382","title":"Identification of D-peptide ligands through mirror-image phage display.","authors":"Schumacher, T N; Mayr, L M; Minor, D L; Milhollen, M A; Burgess, M W; Kim, P S","year":1996,"journal":"Science (New York, N.Y.), 271(5257), 1854-7","doi":null,"pmid":"8596952","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00383","title":"Beneficial effect of a novel pentadecapeptide BPC 157 on gastric lesions induced by restraint stress, ethanol, indomethacin, and capsaicin neurotoxicity.","authors":"Sikirić, P; Seiwerth, S; Grabarević, Z; Rucman, R; Petek, M; Jagić, V; Turković, B; Rotkvić, I; Mise, S; Zoricić, I; Gjurasin, M; Konjevoda, P; Separović, J; Ljubanović, D; Artuković, B; Bratulić, M; Tisljar, M; Jurina, L; Buljat, G; Miklić, P; Marović, A","year":1996,"journal":"Digestive diseases and sciences, 41(8), 1604-14","doi":null,"pmid":"8769287","tags":["bpc-157","gut-healing","inflammation","pain"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"BPC-157 provided strong gastroprotection against four distinct injury types (stress, ethanol, NSAID, capsaicin neurotoxicity), suggesting a broad protective mechanism involving sensory nerve pathways.","whyItMatters":"Showing protection against multiple injury types suggests BPC-157 has a fundamental gastroprotective mechanism, not just anti-acid or anti-inflammatory action, making it potentially useful for various stomach conditions.","specificNumbers":"","methodology":"Animal study testing BPC-157 in rats against gastric lesions from: restraint stress, 96% ethanol, indomethacin (NSAID), and capsaicin nerve damage. Lesion severity was measured and compared to controls.","limitations":"Animal study in rats. Doses and routes of BPC-157 administration not specified in abstract. Mechanism of protection not fully elucidated. No human data."},{"rthcId":"RPEP-00384","title":"Salutary and prophylactic effect of pentadecapeptide BPC 157 on acute pancreatitis and concomitant gastroduodenal lesions in rats.","authors":"Sikirić, P; Seiwerth, S; Grabarević, Z; Rucman, R; Petek, M; Jagić, V; Turković, B; Rotkvić, I; Mise, S; Zoricić, I; Jurina, L; Konjevoda, P; Hanzevacki, M; Ljubanović, D; Separović, J; Gjurasin, M; Bratulić, M; Artuković, B; Jelovac, N; Buljat, G","year":1996,"journal":"Digestive diseases and sciences, 41(7), 1518-26","doi":null,"pmid":"8689934","tags":["bpc-157","gut-healing","inflammation"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"BPC-157 demonstrated both prophylactic and therapeutic effects in bile duct ligation-induced pancreatitis, also improving concomitant gastric and duodenal lesions.","whyItMatters":"Acute pancreatitis has limited treatment options. A peptide that both prevents and heals pancreatic inflammation while also protecting the surrounding digestive tract addresses a significant unmet medical need.","specificNumbers":"","methodology":"Rat model of acute pancreatitis induced by bile duct ligation. BPC-157 was tested as either a pre-treatment (protective) or post-onset treatment (healing). Pancreatitis severity and gastroduodenal lesions were assessed.","limitations":"Animal study using a surgical model of pancreatitis that may not perfectly represent human disease. Specific doses and quantitative results not detailed in abstract."},{"rthcId":"RPEP-00385","title":"Endogenous opioid regulation of hippocampal function.","authors":"Simmons, M L; Chavkin, C","year":1996,"journal":"International review of neurobiology, 39, 145-96","doi":null,"pmid":"8894847","tags":["opioid-peptides","neuroprotection","cognitive-enhancement"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Proenkephalin-derived peptides increase hippocampal excitability via mu/delta receptors, while prodynorphin-derived peptides decrease it via kappa receptors, providing opposing regulation of memory circuits.","whyItMatters":"Understanding how opioid peptides regulate memory circuits has implications for cognitive enhancement, addiction-related memory, and neurodegenerative diseases affecting the hippocampus.","specificNumbers":"","methodology":"Review synthesizing electrophysiological, pharmacological, and neuroanatomical evidence on opioid peptide actions in hippocampal circuits.","limitations":"Review article based primarily on animal electrophysiology data. Translation to human cognitive function is inferred."},{"rthcId":"RPEP-00386","title":"Modulation of pulsatile GH release through a novel receptor in hypothalamus and pituitary gland.","authors":"Smith, R G; Pong, S S; Hickey, G; Jacks, T; Cheng, K; Leonard, R; Cohen, C J; Arena, J P; Chang, C H; Drisko, J; Wyvratt, M; Fisher, M; Nargund, R; Patchett, A","year":1996,"journal":"Recent progress in hormone research, 51, 261-85; discussion 285-6","doi":null,"pmid":"8701083","tags":["ghrp","mk-677","hormone-optimization"],"studyType":"review","evidenceStrength":"strong","keyFinding":"GH secretagogues act through a novel receptor at dual sites (hypothalamus and pituitary) to amplify natural pulsatile GH release rather than creating continuous artificial elevation.","whyItMatters":"Preserving the natural pulsatile pattern of GH release is critical because the body responds differently to pulsed vs. continuous GH. Secretagogues maintain this pattern while boosting output.","specificNumbers":"","methodology":"Review of GH secretagogue mechanisms, receptor characterization, and pulsatile release patterns in preclinical and clinical studies.","limitations":"Review article; some claims about receptor characterization were still preliminary at time of publication. Long-term effects of chronic secretagogue use not fully characterized."},{"rthcId":"RPEP-00387","title":"Airway sensory nerves: a burning issue in asthma?","authors":"Spina, D","year":1996,"journal":"Thorax, 51(3), 335-7","doi":null,"pmid":"8779145","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00388","title":"Endogenous opioid peptides in parasympathetic, sympathetic and sensory nerves in the guinea-pig heart.","authors":"Steele, P A; Aromataris, E C; Riederer, B M","year":1996,"journal":"Cell and tissue research, 284(2), 331-9","doi":null,"pmid":"8625399","tags":["opioid-peptides","cardiovascular","neuropeptides"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Approximately 40% of cardiac ganglion cells contained dynorphin A immunoreactivity, and opioid peptides were found in parasympathetic, sympathetic, and sensory cardiac nerves.","whyItMatters":"Finding opioid peptides in all three cardiac nerve types suggests the heart's opioid system can modulate heart rate, contractility, blood flow, and pain sensing — a comprehensive cardiac regulatory role.","specificNumbers":"","methodology":"Multiple-labeling immunohistochemistry to co-localize opioid peptides with markers for parasympathetic, sympathetic, and sensory nerve types in guinea pig heart tissue.","limitations":"Animal study in guinea pig hearts. Distribution patterns may differ in human hearts. Immunohistochemistry shows presence but not functional activity."},{"rthcId":"RPEP-00389","title":"Inhibition of dynorphin-converting enzymes prolongs the antinociceptive effect of intrathecally administered dynorphin in the mouse formalin test.","authors":"Tan-No, K; Taira, A; Sakurada, T; Inoue, M; Sakurada, S; Tadano, T; Sato, T; Sakurada, C; Nylander, I; Silberring, J; Terenius, L; Kisara, K","year":1996,"journal":"European journal of pharmacology, 314(1-2), 61-7","doi":null,"pmid":"8957219","tags":["opioid-peptides","pain","bioavailability"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Peptidase inhibitors significantly prolonged the antinociceptive effect of intrathecally administered dynorphin A (0.5-2 nmol) and dynorphin B (2-8 nmol) in the formalin test.","whyItMatters":"If dynorphin's rapid breakdown can be slowed, its natural pain-relieving properties could be therapeutically enhanced without using synthetic opioids.","specificNumbers":"","methodology":"Mouse formalin test: dynorphin A or B was injected intrathecally 5 minutes before 0.5% formalin injection into a hindpaw. Pain response was measured with and without co-administered peptidase inhibitors.","limitations":"Mouse study with spinal injection — not a practical administration route. The formalin test models inflammatory pain specifically. Peptidase inhibitor side effects not assessed."},{"rthcId":"RPEP-00390","title":"Once daily subcutaneous growth hormone-releasing hormone therapy accelerates growth in growth hormone-deficient children during the first year of therapy. Geref International Study Group.","authors":"Thorner, M; Rochiccioli, P; Colle, M; Lanes, R; Grunt, J; Galazka, A; Landy, H; Eengrand, P; Shah, S","year":1996,"journal":"The Journal of clinical endocrinology and metabolism, 81(3), 1189-96","doi":null,"pmid":"8772599","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00391","title":"Pituitary responsiveness to GH-releasing hormone, GH-releasing peptide-2 and thyrotrophin-releasing hormone in critical illness.","authors":"Van den Berghe, G; de Zegher, F; Bowers, C Y; Wouters, P; Muller, P; Soetens, F; Vlasselaers, D; Schetz, M; Verwaest, C; Lauwers, P; Bouillon, R","year":1996,"journal":"Clinical endocrinology, 45(3), 341-51","doi":null,"pmid":"8949573","tags":["ghrp","hormone-optimization","clinical-trials"],"studyType":"RCT","evidenceStrength":"strong","keyFinding":"GHRP-2 maintained GH-releasing efficacy in critically ill patients despite blunted responses to GHRH, suggesting a preserved alternative pathway for GH stimulation.","whyItMatters":"Muscle wasting in ICU patients significantly impacts recovery. If GHRP-2 can stimulate GH release when normal pathways are suppressed, it could help preserve muscle mass during critical illness.","specificNumbers":"","methodology":"Clinical study testing pituitary GH responses to GHRH, GHRP-2, and TRH in critically ill patients, comparing to expected normal responses.","limitations":"Clinical study in critically ill patients — a heterogeneous population. Sample size and specific response magnitudes not detailed in abstract. Functional outcomes not assessed."},{"rthcId":"RPEP-00392","title":"Neutral endopeptidase inhibition potentiates the effects of natriuretic peptides in renin transgenic rats.","authors":"Wegner, M; Ganten, D; Stasch, J P","year":1996,"journal":"Hypertension research : official journal of the Japanese Society of Hypertension, 19(4), 229-38","doi":null,"pmid":"8986453","tags":["natriuretic-peptides","cardiovascular","peptide-design"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"NEP inhibition with thiorphan significantly potentiated the blood pressure-lowering, hormonal, and renal effects of all three natriuretic peptides (ANP, BNP, CNP) in hypertensive transgenic rats.","whyItMatters":"This study provided preclinical evidence for the NEP inhibitor strategy that eventually led to the development of sacubitril/valsartan (Entresto), now a standard heart failure treatment.","specificNumbers":"","methodology":"Hypertensive transgenic rats (with extra renin gene) received infusions of ANP, BNP, or CNP with or without the NEP inhibitor (S)-thiorphan. Blood pressure, hormonal, and renal responses were measured.","limitations":"Animal study using genetically modified hypertensive rats. Results may not directly translate to human heart failure. Acute infusion protocol doesn't address chronic treatment effects."},{"rthcId":"RPEP-00393","title":"Role of neutral endopeptidase 24.11 in AV fistular rat model of heart failure.","authors":"Wegner, M; Hirth-Dietrich, C; Stasch, J P","year":1996,"journal":"Cardiovascular research, 31(6), 891-8","doi":null,"pmid":"8759244","tags":["natriuretic-peptides","cardiovascular","kidney"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"NEP activity is increased in volume-overload heart failure, potentially accelerating the breakdown of protective natriuretic peptides even as the heart produces more of them.","whyItMatters":"If NEP destroys protective peptides faster in heart failure, inhibiting NEP could restore the balance between vasodilator and vasoconstrictor forces — a key therapeutic principle.","specificNumbers":"","methodology":"Aortovenocaval fistula rat model of heart failure with measurement of NEP activity, natriuretic peptide levels, and renin-angiotensin-aldosterone system activation.","limitations":"Surgical animal model that may not fully represent human chronic heart failure. NEP activity measurement may not reflect tissue-specific activity."},{"rthcId":"RPEP-00394","title":"Palatability-induced hyperphagia increases hypothalamic Dynorphin peptide and mRNA levels.","authors":"Welch, C C; Kim, E M; Grace, M K; Billington, C J; Levine, A S","year":1996,"journal":"Brain research, 721(1-2), 126-31","doi":null,"pmid":"8793092","tags":["opioid-peptides","weight-loss","neuropeptides"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Ad libitum access to a high-fat/sucrose diet significantly increased hypothalamic dynorphin peptide and mRNA levels compared to standard diet, suggesting opioid peptide-mediated overeating.","whyItMatters":"Understanding the opioid peptide mechanism behind overeating palatable food could lead to targeted interventions for obesity that address the brain chemistry driving excessive food intake.","specificNumbers":"","methodology":"Rats received either cornstarch diet ad libitum, high-fat/sucrose ad libitum, high-fat/sucrose pair-fed to cornstarch calories, or high-fat/sucrose restricted to 60% of ad libitum intake. Hypothalamic dynorphin peptide and mRNA were measured.","limitations":"Animal study in rats. Dietary conditions were controlled but may not perfectly model human eating patterns. Only dynorphin was measured; other opioid peptides may also be affected."},{"rthcId":"RPEP-00395","title":"The effects of GH-releasing peptide-6 (GHRP-6) and GHRP-2 on intracellular adenosine 3',5'-monophosphate (cAMP) levels and GH secretion in ovine and rat somatotrophs.","authors":"Wu, D; Chen, C; Zhang, J; Bowers, C Y; Clarke, I J","year":1996,"journal":"The Journal of endocrinology, 148(2), 197-205","doi":null,"pmid":"8699133","tags":["ghrp","receptor-signaling","hormone-optimization"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"GHRP-2 increased intracellular cAMP (like GHRH) while GHRP-6 released GH without raising cAMP, revealing partially different mechanisms despite similar GH-releasing outcomes.","whyItMatters":"Understanding the signaling differences between GHRPs helps predict their clinical behavior, drug interactions, and optimal combination strategies.","specificNumbers":"","methodology":"In vitro study using partially purified sheep somatotrophs and rat pituitary cells. Intracellular cAMP and GH release were measured after treatment with GHRP-2, GHRP-6, and GRF (GHRH).","limitations":"In vitro study using animal pituitary cells. Species differences may exist. Partially purified somatotrophs may not fully represent in vivo conditions."},{"rthcId":"RPEP-00396","title":"Superiority of brain natriuretic peptide as a hormonal marker of ventricular systolic and diastolic dysfunction and ventricular hypertrophy.","authors":"Yamamoto, K; Burnett, J C; Jougasaki, M; Nishimura, R A; Bailey, K R; Saito, Y; Nakao, K; Redfield, M M","year":1996,"journal":"Hypertension (Dallas, Tex. : 1979), 28(6), 988-94","doi":null,"pmid":"8952587","tags":["natriuretic-peptides","cardiovascular","clinical-trials"],"studyType":"cross-sectional","evidenceStrength":"strong","keyFinding":"BNP was superior to both C-terminal ANP and N-terminal ANP for detecting left ventricular systolic dysfunction, diastolic dysfunction, and ventricular hypertrophy.","whyItMatters":"Having a single blood test that can detect multiple types of heart problems enables efficient screening and early intervention, potentially saving lives through earlier treatment.","specificNumbers":"","methodology":"Cross-sectional study comparing plasma levels of BNP, C-terminal ANP, and N-terminal ANP as diagnostic markers across three types of cardiac dysfunction.","limitations":"Cross-sectional design; specific thresholds and sensitivity/specificity values not detailed in abstract. Patient population characteristics not described."},{"rthcId":"RPEP-00397","title":"Effects of GHRP-2 and hexarelin, two synthetic GH-releasing peptides, on GH, prolactin, ACTH and cortisol levels in man. Comparison with the effects of GHRH, TRH and hCRH.","authors":"Arvat, E; di Vito, L; Maccagno, B; Broglio, F; Boghen, M F; Deghenghi, R; Camanni, F; Ghigo, E","year":1997,"journal":"Peptides, 18(6), 885-91","doi":null,"pmid":"9285939","tags":["ghrp","hormone-optimization","clinical-trials"],"studyType":"RCT","evidenceStrength":"strong","keyFinding":"GHRP-2 and hexarelin both showed potent GH-releasing activity with slight stimulatory effects on prolactin, ACTH, and cortisol; their GH-releasing activities were directly compared for the first time.","whyItMatters":"This head-to-head comparison helps clinicians and researchers choose between the two most popular GHRPs and understand their hormonal side effect profiles.","specificNumbers":"","methodology":"Randomized clinical trial comparing GHRP-2, hexarelin, GHRH, TRH, and CRH administration in healthy men, measuring GH, prolactin, ACTH, and cortisol responses.","limitations":"Acute single-dose study in healthy men only. No women included. Long-term effects and functional outcomes not assessed."},{"rthcId":"RPEP-00398","title":"Growth hormone secretagogues in children with altered growth.","authors":"Bercu, B B; Walker, R F","year":1997,"journal":"Acta paediatrica (Oslo, Norway : 1992). Supplement, 423, 102-6","doi":null,"pmid":"9401554","tags":["ghrp","hormone-optimization","clinical-trials"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"GHRP-2 stimulation revealed significant residual GH secretory potential in children classified as GH-deficient, with peak responses varying by growth disorder type.","whyItMatters":"A more sensitive test for GH reserves could prevent unnecessary GH replacement in children who can still produce their own GH when properly stimulated.","specificNumbers":"","methodology":"Clinical trial using sequential GHRH and GHRP-2 stimulation testing in children with and without GH deficiency. Peak GH responses were measured and compared across diagnostic groups.","limitations":"Clinical trial; specific group sizes and complete numerical results not fully detailed in abstract. Selection criteria for growth disorders may vary between centers."},{"rthcId":"RPEP-00399","title":"Effect of natural amphipathic peptides on viability, membrane potential, cell shape and motility of mollicutes.","authors":"Béven, L; Wróblewski, H","year":1997,"journal":"Research in microbiology, 148(2), 163-75","doi":null,"pmid":"9765797","tags":["antimicrobial-peptides","infection"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Antimicrobial peptide effectiveness against mollicutes varied dramatically by species, with animal defense peptides being less potent than venom and bacterial peptides. Multiple cellular effects preceded killing.","whyItMatters":"Mollicutes (including Mycoplasma) cause pneumonia and other infections and are naturally resistant to many antibiotics because they lack cell walls. Antimicrobial peptides that target membranes could fill this treatment gap.","specificNumbers":"","methodology":"In vitro testing of 10 amphipathic antimicrobial peptides against 6 mollicute species, measuring viability, membrane potential, cell morphology, and motility.","limitations":"In vitro study only. Peptide concentrations effective in culture may not be achievable in vivo. Toxicity to human cells not compared."},{"rthcId":"RPEP-00400","title":"Oral administration of growth hormone (GH) releasing peptide-mimetic MK-677 stimulates the GH/insulin-like growth factor-I axis in selected GH-deficient adults.","authors":"Chapman, I M; Pescovitz, O H; Murphy, G; Treep, T; Cerchio, K A; Krupa, D; Gertz, B; Polvino, W J; Skiles, E H; Pezzoli, S S; Thorner, M O","year":1997,"journal":"The Journal of clinical endocrinology and metabolism, 82(10), 3455-63","doi":null,"pmid":"9329386","tags":["mk-677","hormone-optimization","clinical-trials"],"studyType":"RCT","evidenceStrength":"moderate","keyFinding":"Oral MK-677 stimulated GH and IGF-I in selected severely GH-deficient adults, with responses dependent on residual pituitary secretory capacity.","whyItMatters":"If MK-677 can stimulate GH production in GH-deficient patients, some could potentially switch from daily GH injections to an oral pill, dramatically improving quality of life.","specificNumbers":"","methodology":"Nine severely GH-deficient men (peak GH to insulin: 1.2 ± 1.5 µg/L, range 0.02-4.79) received oral MK-677. GH and IGF-I responses were measured.","limitations":"Very small study (9 patients). Only men. Severely GH-deficient population limits generalizability. Variable responses suggest patient selection criteria are needed."},{"rthcId":"RPEP-00401","title":"Growth hormone releasing peptides: a comparison of the growth hormone releasing activities of GHRP-2 and GHRP-6 in rat primary pituitary cells.","authors":"Cheng, J; Wu, T J; Butler, B; Cheng, K","year":1997,"journal":"Life sciences, 60(16), 1385-92","doi":null,"pmid":"9096259","tags":["ghrp","hormone-optimization"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"GHRP-2 and GHRP-6 each synergize with GRF/GHRH but combining both GHRPs at maximal doses adds no further GH release, confirming shared receptor competition.","whyItMatters":"Confirms that stacking different GHRPs is pointless — they compete for the same receptor. The synergy is between a GHRP and GHRH, not between two GHRPs.","specificNumbers":"","methodology":"In vitro study using rat primary pituitary cells with dose-response testing of GHRP-2, GHRP-6, and GRF alone and in combinations.","limitations":"In vitro rat pituitary cells; may not fully replicate in vivo conditions. Only acute exposure tested."},{"rthcId":"RPEP-00402","title":"Prolonged oral treatment with MK-677, a novel growth hormone secretagogue, improves sleep quality in man.","authors":"Copinschi, G; Leproult, R; Van Onderbergen, A; Caufriez, A; Cole, K Y; Schilling, L M; Mendel, C M; De Lepeleire, I; Bolognese, J A; Van Cauter, E","year":1997,"journal":"Neuroendocrinology, 66(4), 278-86","doi":null,"pmid":"9349662","tags":["mk-677","sleep","hormone-optimization","clinical-trials"],"studyType":"RCT","evidenceStrength":"moderate","keyFinding":"Prolonged oral MK-677 significantly improved sleep quality by increasing stage 4 (deep sleep) and REM sleep in both young (18-30) and older (65+) adults.","whyItMatters":"Sleep quality declines with age alongside GH secretion. A compound that improves both simultaneously could address two major age-related health concerns.","specificNumbers":"","methodology":"Double-blind study with 8 young (18-30) and 6 older (65+) subjects receiving oral MK-677 during treatment periods. Sleep was objectively measured by polysomnography.","limitations":"Small sample sizes (8 young, 6 older). Double-blind but specific study duration and dosing not fully detailed in abstract. Long-term effects unknown."},{"rthcId":"RPEP-00403","title":"Adrenomedullin, endothelin, neuropeptide Y, atrial, brain, and C-natriuretic prohormone peptides compared as early heart failure indicators.","authors":"Daggubati, S; Parks, J R; Overton, R M; Cintron, G; Schocken, D D; Vesely, D L","year":1997,"journal":"Cardiovascular research, 36(2), 246-55","doi":null,"pmid":"9463636","tags":["natriuretic-peptides","cardiovascular"],"studyType":"cross-sectional","evidenceStrength":"moderate","keyFinding":"Simultaneous comparison of six peptide biomarkers in heart failure patients identified the best early CHF indicators across NYHA classes I through IV.","whyItMatters":"Identifying the best early biomarker enables earlier heart failure detection and treatment, potentially preventing progression to severe disease.","specificNumbers":"","methodology":"Cross-sectional study measuring six peptide biomarkers simultaneously in 40 CHF patients (NYHA I-IV) and 10 healthy controls.","limitations":"Small sample sizes per NYHA class. Cross-sectional design doesn't assess predictive value over time."},{"rthcId":"RPEP-00404","title":"Attenuation of the growth hormone secretagogue induction of Fos protein in the rat arcuate nucleus by central somatostatin action.","authors":"Dickson, S L; Viltart, O; Bailey, A R; Leng, G","year":1997,"journal":"Neuroendocrinology, 66(3), 188-94","doi":null,"pmid":"9380276","tags":["ghrp","neuropeptides","hormone-optimization"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Octreotide (somatostatin analog) attenuated GH secretagogue-induced Fos expression in the arcuate nucleus, showing somatostatin opposes GHRP action centrally.","whyItMatters":"Understanding that somatostatin can block GHRP effects in the brain explains why high somatostatin states (like elevated blood sugar) can reduce GHRP efficacy.","specificNumbers":"","methodology":"Conscious male rats received IV octreotide (100 µg) or saline 10 minutes before IV GH secretagogue injection. Brains were processed for Fos protein immunohistochemistry.","limitations":"Animal study using pharmacological somatostatin analog (octreotide) at a specific dose. Natural somatostatin dynamics may differ. Fos expression is an indirect marker."},{"rthcId":"RPEP-00405","title":"Antibacterial peptides of bovine lactoferrin: purification and characterization.","authors":"Dionysius, D A; Milne, J M","year":1997,"journal":"Journal of dairy science, 80(4), 667-74","doi":null,"pmid":"9149961","tags":["antimicrobial-peptides","infection"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Three cationic antibacterial peptides purified from lactoferrin's N-terminus showed activity against enterotoxigenic E. coli, with one being particularly potent.","whyItMatters":"Discovering natural antibacterial peptides in milk protein supports the development of food-derived antimicrobials and helps explain breast milk's protective effects against infant gut infections.","specificNumbers":"","methodology":"Bovine lactoferrin was digested with pepsin and the products were purified. Three peptides with antibacterial activity were isolated and characterized for their antimicrobial properties.","limitations":"In vitro characterization only. Effectiveness in vivo, stability in the gut, and clinical applicability not assessed."},{"rthcId":"RPEP-00406","title":"Vasopressin/serotonin interactions in the anterior hypothalamus control aggressive behavior in golden hamsters.","authors":"Ferris, C F; Melloni, R H; Koppel, G; Perry, K W; Fuller, R W; Delville, Y","year":1997,"journal":"The Journal of neuroscience : the official journal of the Society for Neuroscience, 17(11), 4331-40","doi":null,"pmid":"9151749","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00407","title":"Opioid peptide modulation of circulatory and endocrine response to mental stress in humans.","authors":"Fontana, F; Bernardi, P; Pich, E M; Boschi, S; De Iasio, R; Spampinato, S; Grossi, G","year":1997,"journal":"Peptides, 18(2), 169-75","doi":null,"pmid":"9149287","tags":["opioid-peptides","cardiovascular","anxiety-mood"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"Low blood pressure responders to mental stress had significantly higher beta-endorphin release than high responders, suggesting endogenous opioids buffer the cardiovascular stress response.","whyItMatters":"This human study provides direct evidence that the body's own opioid peptides protect against harmful cardiovascular stress responses, with implications for stress management and heart disease prevention.","specificNumbers":"","methodology":"30 healthy subjects classified by systolic BP response to mental arithmetic: low responders (9.3-15.1% increase, n=15) vs. high responders (35.1-45.4% increase, n=15). Plasma opioid peptides, cortisol, and catecholamines measured during stress.","limitations":"Cross-sectional design cannot establish causation. Correlation between endorphin levels and lower BP response doesn't prove endorphins caused the protection. Mental arithmetic test is one specific type of stress."},{"rthcId":"RPEP-00408","title":"Pressor effects of endogenous opioid system during acute episodes of blood pressure increases in hypertensive patients.","authors":"Fontana, F; Bernardi, P; Spampinato, S; Boschi, S; De Iasio, R; Grossi, G","year":1997,"journal":"Hypertension (Dallas, Tex. : 1979), 29(1 Pt 1), 105-10","doi":null,"pmid":"9039088","tags":["opioid-peptides","cardiovascular"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"Beta-endorphin, met-enkephalin, and dynorphin B levels changed significantly during acute blood pressure increases in hypertensive patients, alongside ANF and endothelin-1 alterations.","whyItMatters":"Understanding the opioid system's role in hypertensive crises could lead to new treatment strategies using opioid pathway modulation for blood pressure management.","specificNumbers":"","methodology":"Clinical trial measuring plasma levels of three opioid peptides, catecholamines, ANF, and endothelin-1 in hypertensive patients before and after naloxone administration during acute BP episodes.","limitations":"Clinical trial in selected hypertensive patients during acute episodes. Small study with limited generalizability. Naloxone has its own cardiovascular effects."},{"rthcId":"RPEP-00409","title":"The influence of BPC 157 on nitric oxide agonist and antagonist induced lesions in broiler chicks.","authors":"Grabarevic, Z; Tisljar, M; Artukovic, B; Bratulic, M; Dzaja, P; Seiwerth, S; Sikiric, P; Peric, J; Geres, D; Kos, J","year":1997,"journal":"Journal of physiology, Paris, 91(3-5), 139-49","doi":null,"pmid":"9403788","tags":["bpc-157","respiratory"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"BPC-157 protected against lesions from both NO agonists and NO antagonists, suggesting a modulatory rather than one-directional effect on nitric oxide signaling.","whyItMatters":"BPC-157's ability to protect against both excess and insufficient NO signaling suggests it acts as a system balancer — a unique property that could explain its wide-ranging protective effects.","specificNumbers":"","methodology":"Broiler chicks pretreated with BPC-157 (10 µg/kg or 10 ng/kg IP) or saline before receiving NO agonists or antagonists. Tissue damage and pulmonary hypertension severity assessed.","limitations":"Animal study in chicks, a model primarily relevant to poultry pulmonary hypertension. Mechanism of NO modulation not fully elucidated."},{"rthcId":"RPEP-00410","title":"Endogenous opioid systems and alcohol addiction.","authors":"Herz, A","year":1997,"journal":"Psychopharmacology, 129(2), 99-111","doi":null,"pmid":"9040115","tags":["opioid-peptides","addiction"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Mu and delta opioid receptors mediate alcohol's rewarding properties while kappa receptors oppose them, with all three endogenous opioid peptide families playing distinct roles in addiction.","whyItMatters":"Understanding which opioid receptors drive alcohol reward vs. aversion could enable more targeted treatments with fewer side effects than broad opioid blockade.","specificNumbers":"","methodology":"Comprehensive review of preclinical and clinical evidence on opioid receptor subtypes and their endogenous peptide ligands in alcohol reward, craving, and addiction.","limitations":"Review article; some claims based on animal data. Individual variation in opioid system genetics affects treatment response."},{"rthcId":"RPEP-00411","title":"Antibacterial activity in bovine lactoferrin-derived peptides.","authors":"Hoek, K S; Milne, J M; Grieve, P A; Dionysius, D A; Smith, R","year":1997,"journal":"Antimicrobial agents and chemotherapy, 41(1), 54-9","doi":null,"pmid":"8980754","tags":["antimicrobial-peptides","infection"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Recombinant chymosin digestion of lactoferrin yielded multiple antimicrobial peptides including lactoferricin B and novel variants with antibacterial activity.","whyItMatters":"Cheese-making naturally liberates antimicrobial peptides from lactoferrin, suggesting fermented dairy products may contain bioactive antimicrobial peptides.","specificNumbers":"","methodology":"Bovine lactoferrin was digested with recombinant chymosin and the resulting peptides purified and tested for antibacterial activity.","limitations":"In vitro characterization only. Whether these peptides survive further digestion and provide antimicrobial benefit in vivo is unknown."},{"rthcId":"RPEP-00412","title":"Immunoneutralization of beta-endorphin blocks prolactin release during suckling without affecting tuberoinfundibular dopaminergic neural activity.","authors":"Jaworski, R P; Callahan, P; Janik, J","year":1997,"journal":"Life sciences, 61(13), 1301-11","doi":null,"pmid":"9324072","tags":["opioid-peptides","hormone-optimization","fertility"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Anti-beta-endorphin antibodies blocked suckling-induced prolactin release without affecting tuberoinfundibular dopaminergic neurons, proving beta-endorphin is an essential mediator.","whyItMatters":"This study definitively established beta-endorphin as a required mediator of breastfeeding-triggered prolactin release, linking the opioid system to reproductive physiology.","specificNumbers":"","methodology":"Lactating rats (days 8-12 post-partum) received anti-beta-endorphin antibodies. Suckling-induced prolactin levels and dopamine neuron activity were measured and compared to controls.","limitations":"Animal study in rats. Immunoneutralization is a specific experimental technique. The mechanism may differ in humans. Only beta-endorphin was neutralized — other opioids may also play roles."},{"rthcId":"RPEP-00413","title":"Dose-dependent protective effect of BPC 157 on capsaicin-induced rhinitis in rats.","authors":"Kalogjera, L; Ries, M; Baudoin, T; Ferencic, Z; Trotic, R; Pegan, B","year":1997,"journal":"European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery, 254 Suppl 1, S9-11","doi":null,"pmid":"9065615","tags":["bpc-157","inflammation"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"BPC-157 at 10 µg/kg provided dose-dependent protection against capsaicin-induced rhinitis, reducing mast cell infiltration, degranulation, and inflammatory cell accumulation.","whyItMatters":"Rhinitis (nasal inflammation) affects hundreds of millions of people. A peptide that reduces mast cell activation and inflammatory infiltration could offer a novel therapeutic approach.","specificNumbers":"","methodology":"Rats pretreated with BPC-157 (10 µg/kg or 10 ng/kg IP) or saline, followed by intranasal capsaicin (0.05 mL/nostril of 1750 nmol/L). Animals euthanized at timepoint for histological assessment.","limitations":"Animal study with chemical (capsaicin) model of rhinitis that may not fully represent allergic rhinitis. Short-term acute model only."},{"rthcId":"RPEP-00414","title":"Galanin receptors: involvement in feeding, pain, depression and Alzheimer's disease.","authors":"Kask, K; Berthold, M; Bartfai, T","year":1997,"journal":"Life sciences, 60(18), 1523-33","doi":null,"pmid":"9126874","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00415","title":"Endocrine and metabolic effects of long-term administration of [Nle27]growth hormone-releasing hormone-(1-29)-NH2 in age-advanced men and women.","authors":"Khorram, O; Laughlin, G A; Yen, S S","year":1997,"journal":"The Journal of clinical endocrinology and metabolism, 82(5), 1472-9","doi":null,"pmid":"9141536","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00416","title":"Effect of enkephalins and endorphins on cytotoxic activity of natural killer cells and macrophages/monocytes in mice.","authors":"Kowalski, J","year":1997,"journal":"European journal of pharmacology, 326(2-3), 251-5","doi":null,"pmid":"9196278","tags":["opioid-peptides","immune-function"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"All five tested opioid peptides enhanced both NK cell and macrophage/monocyte cytotoxic activity when administered by single IP injection in mice.","whyItMatters":"The finding that all major opioid peptide families enhance tumor-fighting immune cells supports the link between endorphin levels and cancer surveillance.","specificNumbers":"","methodology":"Mice received single IP injections of met-enkephalin, leu-enkephalin, proenkephalin, dynorphin-(1-17), or beta-endorphin. NK cell and macrophage cytotoxicity were measured by 51Cr release assay.","limitations":"Animal study with acute single-injection protocol. Doses and mechanisms not detailed. Chronic effects may differ from acute."},{"rthcId":"RPEP-00417","title":"Interaction of the growth hormone releasing peptide hexarelin with somatostatin.","authors":"Massoud, A F; Hindmarsh, P C; Brook, C G","year":1997,"journal":"Clinical endocrinology, 47(5), 537-47","doi":null,"pmid":"9425393","tags":["ghrp","hormone-optimization"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"Hexarelin's GH-releasing effect is significantly modulated by somatostatin tone, with somatostatin withdrawal amplifying the GH response to hexarelin.","whyItMatters":"Understanding the hexarelin-somatostatin interaction explains why GHRPs work best at certain times and informs optimal dosing strategies.","specificNumbers":"","methodology":"Clinical trial testing hexarelin GH response during various somatostatin states (high tone, low tone, withdrawal) in human subjects.","limitations":"Clinical trial with artificial somatostatin manipulation. Natural somatostatin fluctuations may produce different interactions."},{"rthcId":"RPEP-00418","title":"Molecular analysis of rat pituitary and hypothalamic growth hormone secretagogue receptors.","authors":"McKee, K K; Palyha, O C; Feighner, S D; Hreniuk, D L; Tan, C P; Phillips, M S; Smith, R G; Van der Ploeg, L H; Howard, A D","year":1997,"journal":"Molecular endocrinology (Baltimore, Md.), 11(4), 415-23","doi":null,"pmid":"9092793","tags":["ghrp","hormone-optimization","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"GH secretagogue receptors are molecularly confirmed in both pituitary and hypothalamus, using a distinct signal transduction pathway from GHRH.","whyItMatters":"Confirming receptor expression at two sites explains the potency of GH secretagogues and validates the dual-mechanism model of their action.","specificNumbers":"","methodology":"Molecular biology analysis of GHS receptor expression in rat pituitary and hypothalamic tissues, characterizing binding and signaling properties.","limitations":"Rat tissue analysis; receptor characteristics may differ in humans. In vitro molecular analysis doesn't capture in vivo dynamics."},{"rthcId":"RPEP-00419","title":"[Met5]enkephalin and delta2-opioid receptors in the spinal cord are involved in the cold water swimming-induced antinociception in the mouse.","authors":"Mizoguchi, H; Narita, M; Kampine, J P; Tseng, L F","year":1997,"journal":"Life sciences, 61(7), PL81-6","doi":null,"pmid":"9252252","tags":["opioid-peptides","pain"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Cold water swimming-induced analgesia is mediated by met-enkephalin acting on spinal delta-2 opioid receptors, as shown by selective receptor antagonist studies.","whyItMatters":"This study provides a molecular explanation for cold water therapy's pain-relieving effects, supporting the practice of cold exposure for pain management.","specificNumbers":"","methodology":"Mice underwent cold water swimming (4°C, 3 min). Pain response was measured by tail-flick test. Selective opioid receptor antagonists were used intrathecally to identify the specific receptor and peptide involved.","limitations":"Mouse study using extreme cold (4°C). Human responses to cold water may differ. Tail-flick test measures acute pain only."},{"rthcId":"RPEP-00420","title":"Enkephalins modulate differentiation of normal human keratinocytes in vitro.","authors":"Nissen, J B; Kragballe, K","year":1997,"journal":"Experimental dermatology, 6(5), 222-9","doi":null,"pmid":"9450624","tags":["opioid-peptides","skin-repair"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Enkephalins directly modulate the differentiation of normal human keratinocytes in vitro, establishing opioid peptides as regulators of skin cell biology.","whyItMatters":"Finding that opioid peptides directly regulate skin cell behavior opens new understanding of skin diseases like psoriasis and potentially new therapeutic approaches for wound healing.","specificNumbers":"","methodology":"In vitro study exposing normal human keratinocyte cultures to enkephalins and measuring effects on cell differentiation markers.","limitations":"In vitro study with cultured keratinocytes. Cell behavior in culture may not fully represent skin biology in vivo. Specific enkephalin concentrations and differentiation outcomes not detailed."},{"rthcId":"RPEP-00421","title":"Induction of cardiac natriuretic peptide gene expression in rats trained in hypobaric hypoxic conditions.","authors":"Perhonen, M; Takala, T E; Vuolteenaho, O; Mäntymaa, P; Leppäluoto, J; Ruskoaho, H","year":1997,"journal":"The American journal of physiology, 273(1 Pt 2), R344-52","doi":null,"pmid":"9249570","tags":["natriuretic-peptides","cardiovascular"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Endurance training and hypobaric hypoxia independently and combinedly alter ANP and BNP gene expression in rat atrial and ventricular tissue.","whyItMatters":"Understanding how exercise and altitude affect cardiac peptide production helps explain cardiovascular adaptations to training and has implications for altitude training in athletes.","specificNumbers":"","methodology":"Rats assigned to groups: sedentary normoxia, trained normoxia, sedentary hypoxia, trained hypoxia. Cardiac ANP and BNP gene expression measured in atria and ventricles.","limitations":"Animal study; rat cardiac adaptations may differ from human. Hypobaric conditions represent moderate altitude only."},{"rthcId":"RPEP-00422","title":"Treatment effects of intranasal growth hormone releasing peptide-2 in children with short stature.","authors":"Pihoker, C; Badger, T M; Reynolds, G A; Bowers, C Y","year":1997,"journal":"The Journal of endocrinology, 155(1), 79-86","doi":null,"pmid":"9390009","tags":["ghrp","hormone-optimization","clinical-trials"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"Intranasal GHRP-2 effectively stimulated GH release in children with short stature, demonstrating viability of a needle-free delivery route.","whyItMatters":"For children who need GH therapy, a nasal spray could eliminate the need for daily injections — a major quality-of-life improvement for pediatric patients.","specificNumbers":"","methodology":"Clinical trial administering intranasal GHRP-2 to children with short stature and measuring GH responses.","limitations":"Clinical trial; specific treatment outcomes, dosing, duration, and sample size not detailed in abstract. Long-term growth effects not assessed."},{"rthcId":"RPEP-00423","title":"RNA-peptide fusions for the in vitro selection of peptides and proteins.","authors":"Roberts, R W; Szostak, J W","year":1997,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 94(23), 12297-302","doi":null,"pmid":"9356443","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00424","title":"Hypothalamic targets for growth hormone secretagogues.","authors":"Robinson, I C","year":1997,"journal":"Acta paediatrica (Oslo, Norway : 1992). Supplement, 423, 88-91","doi":null,"pmid":"9401551","tags":["ghrp","hormone-optimization","neuropeptides"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"GH secretagogues activate hypothalamic neurons and require an intact GHRH system for full in vivo potency, despite being able to release GH directly from the pituitary.","whyItMatters":"Understanding that GHRPs need a working GHRH system explains why they're less effective in conditions where GHRH neurons are damaged or absent.","specificNumbers":"","methodology":"Review of preclinical evidence from normal and transgenic animal models on hypothalamic targets and neural circuits activated by GH secretagogues.","limitations":"Review based primarily on animal models. Human hypothalamic-pituitary dynamics may differ."},{"rthcId":"RPEP-00425","title":"Role of the prohormone convertase PC3 in the processing of proglucagon to glucagon-like peptide 1.","authors":"Rouillé, Y; Kantengwa, S; Irminger, J C; Halban, P A","year":1997,"journal":"The Journal of biological chemistry, 272(52), 32810-6","doi":null,"pmid":"9407057","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00426","title":"BPC 157's effect on healing.","authors":"Seiwerth, S; Sikiric, P; Grabarevic, Z; Zoricic, I; Hanzevacki, M; Ljubanovic, D; Coric, V; Konjevoda, P; Petek, M; Rucman, R; Turkovic, B; Perovic, D; Mikus, D; Jandrijevic, S; Medvidovic, M; Tadic, T; Romac, B; Kos, J; Peric, J; Kolega, Z","year":1997,"journal":"Journal of physiology, Paris, 91(3-5), 173-8","doi":null,"pmid":"9403790","tags":["bpc-157","wound-healing"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"BPC-157 enhanced all three major healing processes: granulation tissue formation, angiogenesis, and collagen synthesis.","whyItMatters":"Most wound treatments target one aspect of healing. BPC-157's ability to enhance all three major components simultaneously makes it uniquely effective for tissue repair.","specificNumbers":"","methodology":"Animal wound healing experiments assessing BPC-157's effects on granulation tissue, new blood vessel formation, and collagen deposition across various healing models.","limitations":"Animal study; specific wound models, doses, and quantitative results not detailed in abstract. Human clinical data not provided."},{"rthcId":"RPEP-00427","title":"Structure-antitumor and hemolytic activity relationships of synthetic peptides derived from cecropin A-magainin 2 and cecropin A-melittin hybrid peptides.","authors":"Shin, S Y; Lee, M K; Kim, K L; Hahm, K S","year":1997,"journal":"The journal of peptide research : official journal of the American Peptide Society, 50(4), 279-85","doi":null,"pmid":"9352466","tags":["antimicrobial-peptides","cancer"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Hybrid peptides from cecropin A-magainin 2 and cecropin A-melittin showed antitumor activity, with structure-activity relationships enabling separation of cancer-killing from hemolytic effects.","whyItMatters":"Designing peptides that selectively kill cancer cells while sparing normal cells is crucial for developing peptide-based anticancer therapies.","specificNumbers":"","methodology":"In vitro testing of designed hybrid peptides for antitumor activity against cancer cells and hemolytic activity against red blood cells to determine therapeutic selectivity.","limitations":"In vitro study only. Cancer cell killing in a dish doesn't guarantee in vivo efficacy. Stability, bioavailability, and in vivo toxicity not assessed."},{"rthcId":"RPEP-00428","title":"Pentadecapeptide BPC 157 positively affects both non-steroidal anti-inflammatory agent-induced gastrointestinal lesions and adjuvant arthritis in rats.","authors":"Sikiric, P; Seiwerth, S; Grabarevic, Z; Rucman, R; Petek, M; Jagic, V; Turkovic, B; Rotkvic, I; Mise, S; Zoricic, I; Konjevoda, P; Perovic, D; Simicevic, V; Separovic, J; Hanzevacki, M; Ljubanovic, D; Artukovic, B; Bratulic, M; Tisljar, M; Rekic, B; Gjurasin, M; Miklic, P; Buljat, G","year":1997,"journal":"Journal of physiology, Paris, 91(3-5), 113-22","doi":null,"pmid":"9403784","tags":["bpc-157","gut-healing","inflammation","bone-joint"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"BPC-157 both protected against NSAID-induced GI lesions and improved chronic adjuvant arthritis, demonstrating simultaneous gastroprotective and anti-inflammatory effects.","whyItMatters":"NSAIDs are the most common treatment for arthritis but cause serious gut damage. A peptide that protects the gut while also reducing inflammation could solve a major clinical dilemma.","specificNumbers":"","methodology":"Rat model of adjuvant arthritis with concurrent NSAID administration. BPC-157 was tested for both gastroprotective effects (against NSAID damage) and arthritis improvement.","limitations":"Animal study; adjuvant arthritis may not fully model human rheumatoid arthritis. Specific doses, timing, and quantitative improvements not detailed."},{"rthcId":"RPEP-00429","title":"Pentadecapeptide BPC 157, cimetidine, ranitidine, bromocriptine, and atropine effect in cysteamine lesions in totally gastrectromized rats: a model for cytoprotective studies.","authors":"Sikirić, P; Mikus, D; Seiwerth, S; Grabarević, Z; Rucman, R; Petek, M; Jagić, V; Turković, B; Rotkvić, I; Mise, S; Zoricić, I; Perić, J; Konjevoda, P; Perović, D; Jurina, L; Hanzevacki, M; Separović, J; Gjurasin, M; Jadrijević, S; Jelovac, N; Miklić, P; Buljat, G; Marović, A","year":1997,"journal":"Digestive diseases and sciences, 42(5), 1029-37","doi":null,"pmid":"9149058","tags":["bpc-157","gut-healing"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"BPC-157 demonstrated cytoprotective effects in totally gastrectomized (acid-free) rats, proving its mechanism is independent of acid reduction.","whyItMatters":"This proves BPC-157 is a true cytoprotective agent — it protects cells directly, not by reducing acid. This fundamentally different mechanism from antacids means it could help with damage that acid-reducing drugs cannot.","specificNumbers":"","methodology":"Total gastrectomy in rats to create an acid-free environment. Cysteamine-induced lesions were then treated with BPC-157, cimetidine, ranitidine, bromocriptine, or atropine and compared.","limitations":"Total gastrectomy creates an artificial model. The absence of a stomach changes many physiological parameters beyond just acid. Comparison drug results not detailed in abstract."},{"rthcId":"RPEP-00430","title":"Pentadecapeptide BPC 157 interactions with adrenergic and dopaminergic systems in mucosal protection in stress.","authors":"Sikirić, P; Mazul, B; Seiwerth, S; Grabarević, Z; Rucman, R; Petek, M; Jagić, V; Turković, B; Rotkvić, I; Mise, S; Zoricić, I; Jurina, L; Konjevoda, P; Hanzevacki, M; Gjurasin, M; Separović, J; Ljubanović, D; Artuković, B; Bratulić, M; Tisljar, M; Miklić, P; Sumajstorcić, J","year":1997,"journal":"Digestive diseases and sciences, 42(3), 661-71","doi":null,"pmid":"9073154","tags":["bpc-157","gut-healing","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"BPC-157's mucosal protection in stress involves interactions with both adrenergic and dopaminergic neurotransmitter systems.","whyItMatters":"Understanding that BPC-157 works through neurotransmitter systems explains how it protects multiple organ systems — it modulates the central stress response, not just local tissue.","specificNumbers":"","methodology":"Animal study testing BPC-157's gastroprotective effects in stress-induced lesion models with pharmacological manipulation of adrenergic and dopaminergic pathways.","limitations":"Animal study with pharmacological manipulation. Specific agonists/antagonists used and quantitative results not detailed in abstract."},{"rthcId":"RPEP-00431","title":"The influence of a novel pentadecapeptide, BPC 157, on N(G)-nitro-L-arginine methylester and L-arginine effects on stomach mucosa integrity and blood pressure.","authors":"Sikirić, P; Seiwerth, S; Grabarević, Z; Rucman, R; Petek, M; Jagić, V; Turković, B; Rotkvić, I; Mise, S; Zoricić, I; Konjevoda, P; Perović, D; Jurina, L; Separović, J; Hanzevacki, M; Artuković, B; Bratulić, M; Tisljar, M; Gjurasin, M; Miklić, P; Stancić-Rokotov, D; Slobodnjak, Z; Jelovac, N; Marović, A","year":1997,"journal":"European journal of pharmacology, 332(1), 23-33","doi":null,"pmid":"9298922","tags":["bpc-157","cardiovascular","gut-healing"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"BPC-157 counteracted both L-NAME (NO blocker) and L-arginine (NO donor) effects on gastric mucosa and blood pressure, confirming its role as an NO system modulator.","whyItMatters":"BPC-157's ability to normalize NO signaling in both directions explains its broad protective effects across many organ systems.","specificNumbers":"","methodology":"Rats challenged with ethanol-induced gastric lesions and IV blood pressure measurements while receiving L-NAME, L-arginine, or combinations with BPC-157 at two doses.","limitations":"Animal study with pharmacological NO manipulation. The doses of L-NAME used create extreme NO blockade not seen physiologically."},{"rthcId":"RPEP-00432","title":"Levels of dynorphin peptides in the central nervous system and pituitary gland of the spontaneously hypertensive rat.","authors":"Tan-No, K; Terenius, L; Silberring, J; Nylander, I","year":1997,"journal":"Neurochemistry international, 31(1), 27-32","doi":null,"pmid":"9185161","tags":["opioid-peptides","cardiovascular"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Spontaneously hypertensive rats had significantly lower dynorphin A and B levels in the hypothalamus and pituitary compared to normotensive rats.","whyItMatters":"If low dynorphin levels contribute to hypertension, enhancing endogenous opioid peptide activity could represent a novel approach to blood pressure management.","specificNumbers":"","methodology":"Comparison of dynorphin A and B levels by radioimmunoassay across brain regions, spinal cord, and pituitary in SHRs vs. normotensive Wistar-Kyoto rats.","limitations":"Animal model; SHR genetics involve multiple factors beyond opioid peptides. Correlation doesn't prove causation — low dynorphin could be a result rather than cause of hypertension."},{"rthcId":"RPEP-00433","title":"Milk protein-derived opioid receptor ligands.","authors":"Teschemacher, H; Koch, G; Brantl, V","year":1997,"journal":"Biopolymers, 43(2), 99-117","doi":null,"pmid":"9216246","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00434","title":"Growth hormone-releasing hormone and growth hormone-releasing peptide as therapeutic agents to enhance growth hormone secretion in disease and aging.","authors":"Thorner, M O; Chapman, I M; Gaylinn, B D; Pezzoli, S S; Hartman, M L","year":1997,"journal":"Recent progress in hormone research, 52, 215-44; discussion 244-6","doi":null,"pmid":"9238854","tags":["ghrp","mk-677","hormone-optimization","anti-aging"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"GHRH and GHRPs can restore GH secretion in aging and disease, addressing the visceral fat accumulation and metabolic changes associated with GH decline.","whyItMatters":"Age-related GH decline affects virtually everyone, contributing to body composition changes and metabolic deterioration. Secretagogue therapy offers a practical, physiological approach to restoring youthful GH levels.","specificNumbers":"","methodology":"Review chapter discussing the pathophysiology of GH decline and the therapeutic potential of GHRH and GHRPs across aging and disease states.","limitations":"Review chapter; long-term safety of chronic GH stimulation in aging not fully established. Cancer risk with chronically elevated GH/IGF-1 is debated."},{"rthcId":"RPEP-00435","title":"Attenuation of compensation of endogenous cardiac natriuretic peptide system in chronic heart failure: prognostic role of plasma brain natriuretic peptide concentration in patients with chronic symptomatic left ventricular dysfunction.","authors":"Tsutamoto, T; Wada, A; Maeda, K; Hisanaga, T; Maeda, Y; Fukai, D; Ohnishi, M; Sugimoto, Y; Kinoshita, M","year":1997,"journal":"Circulation, 96(2), 509-16","doi":null,"pmid":"9244219","tags":["natriuretic-peptides","cardiovascular"],"studyType":"cohort","evidenceStrength":"strong","keyFinding":"Plasma BNP concentration provided superior prognostic value compared to plasma ANP and other established variables in chronic symptomatic left ventricular dysfunction.","whyItMatters":"Better prognostic markers help clinicians identify high-risk heart failure patients who need more aggressive treatment, potentially saving lives through earlier intervention.","specificNumbers":"","methodology":"Cohort study comparing plasma BNP and ANP as prognostic markers in patients with chronic symptomatic CHF alongside other established prognostic variables.","limitations":"Cohort study; specific outcome endpoints, follow-up duration, and sample size not detailed in abstract."},{"rthcId":"RPEP-00436","title":"The somatotropic axis in critical illness: effect of continuous growth hormone (GH)-releasing hormone and GH-releasing peptide-2 infusion.","authors":"Van den Berghe, G; de Zegher, F; Veldhuis, J D; Wouters, P; Awouters, M; Verbruggen, W; Schetz, M; Verwaest, C; Lauwers, P; Bouillon, R; Bowers, C Y","year":1997,"journal":"The Journal of clinical endocrinology and metabolism, 82(2), 590-9","doi":null,"pmid":"9024260","tags":["ghrp","hormone-optimization","clinical-trials"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"Continuous GHRH plus GHRP-2 infusion partially restored GH pulsatility and substantially raised IGF-1 levels in critically ill patients with suppressed somatotropic axes.","whyItMatters":"ICU muscle wasting significantly impacts recovery and survival. Restoring the GH/IGF-1 axis through secretagogues rather than GH injections may be safer and more effective.","specificNumbers":"","methodology":"Clinical trial using continuous IV infusion of combined GHRH and GHRP-2 in critically ill patients, measuring GH secretion profiles and IGF-1 levels.","limitations":"Clinical trial in heterogeneous critically ill population. Functional outcomes (muscle preservation, recovery) not assessed. Comparison to GH replacement not included."},{"rthcId":"RPEP-00437","title":"Thyrotrophin and prolactin release in prolonged critical illness: dynamics of spontaneous secretion and effects of growth hormone-secretagogues.","authors":"Van den Berghe, G; de Zegher, F; Veldhuis, J D; Wouters, P; Gouwy, S; Stockman, W; Weekers, F; Schetz, M; Lauwers, P; Bouillon, R; Bowers, C Y","year":1997,"journal":"Clinical endocrinology, 47(5), 599-612","doi":null,"pmid":"9425400","tags":["ghrp","hormone-optimization","clinical-trials"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"Prolonged critical illness disrupts spontaneous TSH and prolactin secretion, and GH secretagogue infusion affects these hormones alongside GH stimulation.","whyItMatters":"GH secretagogues in the ICU aren't just affecting GH — they influence the entire hormonal milieu, which must be understood for safe clinical use.","specificNumbers":"","methodology":"Clinical study measuring dynamic TSH and PRL secretion profiles during prolonged critical illness, with and without GH secretagogue infusion.","limitations":"Clinical study in critically ill patients — a heterogeneous population. Specific GH secretagogue used, doses, and outcomes not detailed."},{"rthcId":"RPEP-00438","title":"Opioid peptide gene expression in the primary hereditary cardiomyopathy of the Syrian hamster. III. Autocrine stimulation of prodynorphin gene expression by dynorphin B.","authors":"Ventura, C; Pintus, G","year":1997,"journal":"The Journal of biological chemistry, 272(10), 6699-705","doi":null,"pmid":"9045702","tags":["opioid-peptides","cardiovascular","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Dynorphin B induces dose-dependent autocrine stimulation of its own gene expression in cardiac myocytes, creating a self-amplifying loop that is exaggerated in cardiomyopathy.","whyItMatters":"An autocrine opioid peptide amplification loop in the heart could represent a therapeutic target for treating cardiomyopathy by breaking the self-reinforcing cycle.","specificNumbers":"","methodology":"In vitro study using normal and cardiomyopathic hamster cardiac myocytes. Exogenous dynorphin B was added and prodynorphin mRNA levels and gene transcription were measured.","limitations":"In vitro hamster cardiomyocyte study. The specific cardiomyopathy model (BIO 14.6) may not represent all human cardiomyopathies."},{"rthcId":"RPEP-00439","title":"The role of protein kinase C in GH secretion induced by GH-releasing factor and GH-releasing peptides in cultured ovine somatotrophs.","authors":"Wu, D; Clarke, I J; Chen, C","year":1997,"journal":"The Journal of endocrinology, 154(2), 219-30","doi":null,"pmid":"9291832","tags":["ghrp","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"GRF and GHRP-2 both require PKC translocation for GH release, while GHRP-6 releases GH through a PKC-independent mechanism in ovine somatotrophs.","whyItMatters":"Understanding the signaling differences between GHRPs explains their different clinical profiles and informs rational drug design.","specificNumbers":"","methodology":"Cultured sheep somatotrophs treated with GRF, GHRP-2, or GHRP-6. PKC translocation (cytosol to membrane) and GH release measured with and without PKC inhibitors.","limitations":"In vitro ovine pituitary cells; may differ from human tissue. Only one PKC inhibitor tested."},{"rthcId":"RPEP-00440","title":"[Met]enkephalin in the spinal cord is involved in the antinociception induced by intracerebroventricularly-administered etorphine in the mouse.","authors":"Xu, J Y; Tseng, L F","year":1997,"journal":"Neuroscience, 80(2), 579-85","doi":null,"pmid":"9284359","tags":["opioid-peptides","pain"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Intracerebroventricular etorphine increases met-enkephalin release in the spinal cord, and this spinal opioid mechanism accounts for a significant portion of the observed pain relief.","whyItMatters":"Understanding how the brain's pain control system uses enkephalin peptides in the spinal cord could lead to more targeted pain therapies that work with the body's natural opioid systems rather than relying solely on external drugs.","specificNumbers":"","methodology":"In vivo mouse study using intracerebroventricular drug administration, tail-flick antinociception testing, spinal microdialysis to measure peptide release, and opioid receptor antagonists to identify receptor subtypes.","limitations":"Mouse model may not fully translate to human pain processing. Only one opioid agonist (etorphine) was tested. Spinal microdialysis provides regional but not cellular-level resolution of peptide release."},{"rthcId":"RPEP-00441","title":"Apoptosis in human leukemic cells induced by lactoferricin, a bovine milk protein-derived peptide: involvement of reactive oxygen species.","authors":"Yoo, Y C; Watanabe, R; Koike, Y; Mitobe, M; Shimazaki, K; Watanabe, S; Azuma, I","year":1997,"journal":"Biochemical and biophysical research communications, 237(3), 624-8","doi":null,"pmid":"9299415","tags":["antimicrobial-peptides","cancer"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Lactoferricin B at concentrations up to 50 μg/ml induced dose- and time-dependent apoptosis in THP-1 human monocytic leukemia cells, with reactive oxygen species playing a key mechanistic role.","whyItMatters":"Identifying natural food-derived peptides with anticancer activity opens possibilities for novel therapeutic agents with potentially better safety profiles than conventional chemotherapy drugs.","specificNumbers":"","methodology":"In vitro cell culture study using THP-1 human monocytic leukemia cells, apoptosis assays, ROS measurement, and antioxidant intervention to confirm the oxidative stress mechanism.","limitations":"Single cell line tested (THP-1). In vitro only — no animal or human data. Selectivity for cancer cells over normal cells not fully characterized. Bovine-derived peptide may have different activity than human lactoferricin."},{"rthcId":"RPEP-00442","title":"A potent and selective endogenous agonist for the mu-opiate receptor.","authors":"Zadina, J E; Hackler, L; Ge, L J; Kastin, A J","year":1997,"journal":"Nature, 386(6624), 499-502","doi":null,"pmid":"9087409","tags":["opioid-peptides","pain","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"strong","keyFinding":"Two novel tetrapeptides, endomorphin-1 (Tyr-Pro-Trp-Phe-NH2) and endomorphin-2 (Tyr-Pro-Phe-Phe-NH2), were identified as potent and selective endogenous agonists of the mu-opioid receptor.","whyItMatters":"This discovery filled a major gap in opioid biology — the missing endogenous ligand for the mu receptor. Understanding the body's own mu-opioid system could lead to pain treatments that mimic natural mechanisms with fewer side effects than morphine.","specificNumbers":"","methodology":"Peptide isolation from bovine brain, receptor binding assays across opioid receptor subtypes (mu, delta, kappa), and functional activity testing to establish selectivity and potency.","limitations":"Initial discovery paper — full physiological roles not yet characterized. Brain distribution and biosynthetic pathway were not fully mapped. The precursor protein for endomorphins remained elusive."},{"rthcId":"RPEP-00443","title":"Somatostatin receptor subtype 2 knockout mice are refractory to growth hormone-negative feedback on arcuate neurons.","authors":"Zheng, H; Bailey, A; Jiang, M H; Honda, K; Chen, H Y; Trumbauer, M E; Van der Ploeg, L H; Schaeffer, J M; Leng, G; Smith, R G","year":1997,"journal":"Molecular endocrinology (Baltimore, Md.), 11(11), 1709-17","doi":null,"pmid":"9328352","tags":["ghrp","hormone-optimization","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"SSTR2 knockout mice showed no growth hormone negative feedback on arcuate nucleus neurons, demonstrating that this receptor subtype is essential for GH autoregulation.","whyItMatters":"Understanding the specific receptor responsible for GH feedback has direct implications for GH secretagogue therapy — drugs like GHRP and MK-677 work within this same regulatory system, and knowing which receptors control feedback helps predict and optimize therapeutic responses.","specificNumbers":"","methodology":"Knockout mouse model with genetic deletion of SSTR2, electrophysiological recording of arcuate nucleus neurons, and GH administration to test feedback responses.","limitations":"Knockout models may have compensatory changes during development. Mouse GH physiology differs from humans in some respects. Only arcuate nucleus was studied — other brain regions also participate in GH regulation."},{"rthcId":"RPEP-00444","title":"Soto 1998 Beta Sheet Breaker Peptides","authors":"","year":1998,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00445","title":"Presence of growth hormone secretagogue receptor messenger ribonucleic acid in human pituitary tumors and rat GH3 cells.","authors":"Adams, E F; Huang, B; Buchfelder, M; Howard, A; Smith, R G; Feighner, S D; van der Ploeg, L H; Bowers, C Y; Fahlbusch, R","year":1998,"journal":"The Journal of clinical endocrinology and metabolism, 83(2), 638-42","doi":null,"pmid":"9467586","tags":["ghrp","cancer","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"GHS-R type 1a (active) and type 1b (inactive) mRNA was detected in human pituitary tumor tissue and rat GH3 cells via RT-PCR, confirming these tumors express the GHRP receptor.","whyItMatters":"The presence of functional GHRP receptors in pituitary tumors has clinical implications: GHRP stimulation tests could help diagnose pituitary adenomas, and understanding receptor expression patterns may reveal how these tumors maintain or lose normal regulatory controls.","specificNumbers":"","methodology":"RT-PCR analysis of GHS-R mRNA expression in surgically removed human pituitary adenomas and rat GH3 cell lines, with comparison of type 1a vs. 1b receptor isoform expression.","limitations":"mRNA detection doesn't confirm functional protein expression. Limited number of tumor samples. Tumor heterogeneity means not all pituitary adenomas may show the same receptor profile."},{"rthcId":"RPEP-00446","title":"Altered release of prostaglandins by opioids contributes to impaired cerebral hemodynamics following brain injury.","authors":"Al-Turki, A; Armstead, W M","year":1998,"journal":"Critical care medicine, 26(5), 917-25","doi":null,"pmid":"9590323","tags":["opioid-peptides","neuroprotection"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Fluid percussion brain injury in newborn pigs impaired opioid-mediated cerebral artery dilation by disrupting prostaglandin release pathways, blunting the normal vasodilatory response.","whyItMatters":"Understanding how brain injury disrupts endogenous opioid peptide signaling could lead to neuroprotective strategies that restore these natural protective mechanisms after traumatic brain injury.","specificNumbers":"","methodology":"Newborn pig model of fluid percussion brain injury, pial artery observation through cranial window, opioid peptide application, prostaglandin measurement, and pharmacological intervention to identify disrupted pathways.","limitations":"Newborn pig model — may not fully represent adult human TBI pathophysiology. Acute injury model doesn't capture chronic changes. Specific opioid peptide subtypes' individual contributions not fully separated."},{"rthcId":"RPEP-00447","title":"Pineal peptide preparation epithalamin increases the lifespan of fruit flies, mice and rats.","authors":"Anisimov, V N; Mylnikov, S V; Oparina, T I; Khavinson, V Kh","year":1998,"journal":"Mechanisms of ageing and development, 103(2), 123-32","doi":"10.1016/S0047-6374(98)00034-7","pmid":"9701766","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00448","title":"A new series of highly potent growth hormone-releasing peptides derived from ipamorelin.","authors":"Ankersen, M; Johansen, N L; Madsen, K; Hansen, B S; Raun, K; Nielsen, K K; Thogersen, H; Hansen, T K; Peschke, B; Lau, J; Lundt, B F; Andersen, P H","year":1998,"journal":"Journal of medicinal chemistry, 41(19), 3699-704","doi":null,"pmid":"9733495","tags":["ipamorelin","peptide-design","hormone-optimization"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Sequential backbone modifications of ipamorelin produced smaller peptidomimetic compounds that retained potent GH secretagogue activity, advancing the goal of orally active GH-releasing peptides.","whyItMatters":"Oral bioavailability is a major challenge for peptide therapeutics. This work shows that ipamorelin's core activity can be preserved in smaller, more drug-like molecules, bringing the goal of an oral GH secretagogue closer to reality.","specificNumbers":"","methodology":"Medicinal chemistry study involving systematic structural modification of ipamorelin, synthesis of peptidomimetic analogs, and in vitro/in vivo GH release assays to evaluate potency.","limitations":"Published in 1998 — oral bioavailability data may be preliminary. In vivo pharmacokinetics not fully characterized. Long-term safety of novel peptidomimetics unknown."},{"rthcId":"RPEP-00449","title":"The nonpeptide growth hormone secretagogue, MK-0677, activates hypothalamic arcuate nucleus neurons in vivo.","authors":"Bailey, A R; Smith, R G; Leng, G","year":1998,"journal":"Journal of neuroendocrinology, 10(2), 111-8","doi":null,"pmid":"9535057","tags":["mk-677","ghrp","neuropeptides"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"MK-0677 induced c-Fos expression in arcuate nucleus neurons in vivo, confirming direct hypothalamic activation as a mechanism for its GH-releasing effect.","whyItMatters":"Confirming that MK-677 works through the hypothalamus (not just the pituitary) means it activates the body's natural GH-releasing pathway, which helps explain why it produces physiological pulsatile GH release rather than unnatural continuous elevation.","specificNumbers":"","methodology":"In vivo rat study using systemic MK-0677 administration, immunohistochemistry for c-Fos (neuronal activation marker), and anatomical mapping of activated neurons in the hypothalamus.","limitations":"Rat model — human hypothalamic anatomy differs somewhat. c-Fos is an indirect marker of activation. Single time point analysis doesn't capture dynamic neuronal responses."},{"rthcId":"RPEP-00450","title":"Synthesis and biological activities of phenyl piperazine-based peptidomimetic growth hormone secretagogues.","authors":"Barakat, K J; Cheng, K; Chan, W W; Butler, B S; Jacks, T M; Schleim, K D; Hora, D F; Hickey, G J; Smith, R G; Patchett, A A; Nargund, R P","year":1998,"journal":"Bioorganic & medicinal chemistry letters, 8(11), 1431-6","doi":null,"pmid":"9871779","tags":["ghrp","peptide-design","hormone-optimization"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Phenyl piperazine-based peptidomimetics were identified as potent, orally active GH secretagogues by mimicking privileged structural motifs from known GH-releasing compounds.","whyItMatters":"Discovering new chemical scaffolds for GH secretagogues expands the options for developing oral GH-releasing drugs, potentially leading to compounds with better pharmacological profiles than existing options.","specificNumbers":"","methodology":"Medicinal chemistry approach using structure-activity relationship analysis, synthesis of novel phenyl piperazine compounds, and in vitro/in vivo GH release testing.","limitations":"Short abstract with limited detail on pharmacokinetic properties. Long-term safety data not available. How these compounds compare to MK-677 in clinical settings is unknown."},{"rthcId":"RPEP-00451","title":"Immuno-, phagocytosis-modulating, and antitoxic properties of amino acids and peptide preparations.","authors":"Belokrylov, G A; Derevnina, O Y; Molchanova, I V; Sorochinskaya, E I","year":1998,"journal":"Drug development and industrial pharmacy, 24(2), 115-27","doi":null,"pmid":"15605441","tags":["antimicrobial-peptides","immune-function"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Specific amino acid and peptide preparations enhanced immune responses, increased phagocytic activity, and protected splenocytes from benzene and aflatoxin B1 toxicity.","whyItMatters":"Demonstrating that simple peptide preparations can boost immunity and protect cells from environmental toxins highlights the potential for peptide-based interventions in immune support and detoxification.","specificNumbers":"","methodology":"In vivo and in vitro studies in CBA mice and broiler chickens measuring antibody production, phagocytosis rates, and splenocyte survival following exposure to benzene and aflatoxin B1.","limitations":"Animal study (mice and chickens) — human translation uncertain. Specific peptide compositions not fully characterized. Broiler chicken model has limited clinical relevance. Mechanism of toxin protection not fully elucidated."},{"rthcId":"RPEP-00452","title":"Single-nucleotide polymorphism in the human mu opioid receptor gene alters beta-endorphin binding and activity: possible implications for opiate addiction.","authors":"Bond, C; LaForge, K S; Tian, M; Melia, D; Zhang, S; Borg, L; Gong, J; Schluger, J; Strong, J A; Leal, S M; Tischfield, J A; Kreek, M J; Yu, L","year":1998,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 95(16), 9608-13","doi":null,"pmid":"9689128","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The A118G single-nucleotide polymorphism in the mu opioid receptor gene has an allelic frequency of approximately 10%, with significant differences in distribution across ethnic groups. The variant receptor showed:\n\n- Approximately 3x tighter binding of beta-endorphin compared to the common receptor form\n- Approximately 3x greater potency of beta-endorphin in activating G protein-coupled potassium channels\n- No altered binding for most other opioid peptides and alkaloid drugs (morphine, heroin, fentanyl, methadone)\n\nThe specificity of the effect to beta-endorphin (the endogenous peptide) rather than exogenous opioids is notable, as it suggests this variant primarily affects the body's natural opioid signaling rather than drug pharmacology.","whyItMatters":"This landmark study was one of the first to show that a common genetic variation could alter how the body responds to its own endorphin peptides. The finding has profound implications: if 10% of people have receptors that respond three times more strongly to beta-endorphin, this could influence their baseline pain sensitivity, reward processing, stress responses, and potentially their vulnerability to opioid addiction — all driven by a single nucleotide change.","specificNumbers":"","methodology":"DNA was sequenced from 113 former heroin addicts in methadone maintenance treatment and 39 control individuals with no history of drug or alcohol abuse. Five SNPs were identified in the mu opioid receptor coding region. The A118G variant receptor was expressed in cell culture systems and tested for binding affinity with multiple opioid peptides and drugs, and for functional activity via G protein-coupled potassium channel activation assays.","limitations":"The study used a relatively small sample (152 individuals) and the heroin addict cohort may not be representative of the general population. While the binding and signaling differences are clear in vitro, translating these to real-world addiction risk requires population-level studies. The ethnic variation in allele frequency was noted but not fully characterized. Subsequent studies have debated the strength of the association between A118G and addiction risk."},{"rthcId":"RPEP-00453","title":"Growth hormone-releasing peptide (GHRP).","authors":"Bowers, C Y","year":1998,"journal":"Cellular and molecular life sciences : CMLS, 54(12), 1316-29","doi":null,"pmid":"9893708","tags":["ghrp","hormone-optimization"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"GHRPs release GH through a unique dual and complementary mechanism acting on both the hypothalamus and pituitary, via a specific receptor distinct from the GHRH receptor.","whyItMatters":"This review consolidated the understanding of how GHRPs work at a pivotal time — just after the GHS receptor was cloned — providing a comprehensive framework for researchers and clinicians entering the field.","specificNumbers":"","methodology":"Review article synthesizing published research on GHRP chemistry, pharmacology, receptor characterization, and clinical studies.","limitations":"Review article — no new original data. Represents 1998 state of knowledge; significant advances occurred subsequently, including the discovery of ghrelin in 1999."},{"rthcId":"RPEP-00454","title":"Prolonged stability of brain natriuretic peptide: importance for non-invasive assessment of cardiac function in clinical practice.","authors":"Buckley, M G; Marcus, N J; Yacoub, M H; Singer, D R","year":1998,"journal":"Clinical science (London, England : 1979), 95(3), 235-9","doi":null,"pmid":"9730841","tags":["natriuretic-peptides","cardiovascular"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"BNP showed prolonged stability at room temperature in blood samples, significantly outlasting ANP stability, making BNP the preferred clinical biomarker for cardiac function assessment.","whyItMatters":"For a biomarker to be useful in everyday clinical practice, it needs to survive real-world sample handling. BNP's stability at room temperature removed a major obstacle to its adoption as a routine heart failure test, which has since become standard practice worldwide.","specificNumbers":"","methodology":"Blood samples from heart failure patients collected and stored at room temperature, with BNP and ANP levels measured at serial time points to assess degradation rates.","limitations":"Specific to blood sample handling conditions tested. Other pre-analytical variables (freezing, anticoagulant type) may also affect results. Study focused on stability, not diagnostic accuracy."},{"rthcId":"RPEP-00455","title":"Efficacy of thymosin alpha1 in patients with chronic hepatitis B: a randomized, controlled trial.","authors":"Chien, R N; Liaw, Y F; Chen, T C; Yeh, C T; Sheen, I S","year":1998,"journal":"Hepatology (Baltimore, Md.), 27(5), 1383-7","doi":null,"pmid":"9581695","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00456","title":"Cerebrospinal fluid vasopressin levels: correlates with aggression and serotonin function in personality-disordered subjects.","authors":"Coccaro, E F; Kavoussi, R J; Hauger, R L; Cooper, T B; Ferris, C F","year":1998,"journal":"Archives of general psychiatry, 55(8), 708-14","doi":null,"pmid":"9707381","tags":["neuropeptides","behavioral"],"studyType":"cross-sectional","evidenceStrength":"preliminary","keyFinding":"Cerebrospinal fluid levels of arginine vasopressin (AVP) were directly correlated with life history of general aggression and aggression against persons in people with personality disorders. Higher vasopressin in the brain was linked to more aggressive behavior.\n\nImportantly, vasopressin levels were inversely correlated with serotonin function (measured by prolactin response to d-fenfluramine), and lower serotonin function was also linked to greater aggression. However, the relationship between vasopressin and aggression remained significant even after accounting for serotonin's influence, suggesting vasopressin has its own independent role in promoting aggressive behavior beyond the well-known serotonin connection.","whyItMatters":"This study was among the first to demonstrate in humans what animal research had long suggested: that vasopressin, a peptide hormone primarily known for regulating water balance and blood pressure, also plays a role in aggressive behavior in the brain. By showing that vasopressin promotes aggression through a pathway independent of serotonin, it opened up a potential new target for managing pathological aggression in personality disorders.","specificNumbers":"n=26 personality-disordered subjects · CSF AVP correlated with general aggression and aggression against persons · Inverse correlation between CSF AVP and PRL[d-FEN] serotonin index · AVP-aggression link persisted after controlling for serotonin variance","methodology":"Researchers collected cerebrospinal fluid from 26 adults meeting DSM-IV criteria for personality disorder. They measured vasopressin (AVP) and serotonin metabolite (5-HIAA) levels in the spinal fluid. Serotonin function was also assessed using a d-fenfluramine challenge test, which measures prolactin release as a proxy for central serotonin activity. Aggression was quantified using the Life History of Aggression assessment, and impulsivity was measured with the Barratt Impulsiveness Scales. Statistical correlations were then calculated between the biological markers and behavioral measures.","limitations":"The sample size of 26 is very small, limiting statistical power and generalizability. The cross-sectional design cannot establish whether high vasopressin causes aggression or is a consequence of it. Only personality-disordered subjects were included, so findings may not apply to the general population. CSF sampling captures a single time point and may not reflect dynamic fluctuations in neuropeptide levels."},{"rthcId":"RPEP-00457","title":"Effects of repeated doses and continuous infusions of the growth hormone-releasing peptide hexarelin in conscious male rats.","authors":"Conley, L K; Gaillard, R C; Giustina, A; Brogan, R S; Wehrenberg, W B","year":1998,"journal":"The Journal of endocrinology, 158(3), 367-75","doi":null,"pmid":"9846166","tags":["ghrp","hormone-optimization","cycling"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Pulsatile hexarelin dosing maintained GH-releasing efficacy with modest desensitization, while continuous infusion caused marked attenuation of GH response, supporting intermittent dosing strategies.","whyItMatters":"This study provides direct evidence for why GHRP dosing protocols emphasize pulsatile rather than continuous administration. The body's GH secretagogue receptors desensitize with continuous stimulation, meaning timing and dosing frequency are critical for maintaining therapeutic benefit.","specificNumbers":"","methodology":"In vivo rat study comparing IV, subcutaneous, and oral repeated dosing versus continuous IV infusion of hexarelin, with serial GH measurements to quantify response patterns.","limitations":"Rat study — desensitization kinetics may differ in humans. Short-term study — long-term desensitization patterns not characterized. Only hexarelin tested — other GHRPs may show different desensitization profiles."},{"rthcId":"RPEP-00458","title":"Accelerated in vitro fibril formation by a mutant alpha-synuclein linked to early-onset Parkinson disease.","authors":"Conway, K A; Harper, J D; Lansbury, P T","year":1998,"journal":"Nature medicine, 4(11), 1318-20","doi":null,"pmid":"9809558","tags":[],"studyType":"in-vitro","evidenceStrength":"early","keyFinding":"Both mutant forms of alpha-synuclein (A53T and A30P), which are linked to early-onset Parkinson's disease, form Lewy body-like fibrils more rapidly than the wild-type protein in test-tube conditions. The A53T mutation produced fibrils fastest. All three forms of alpha-synuclein were disordered at low concentrations, but at higher concentrations they assembled into fibrils and spherical structures characteristic of the brain inclusions seen in Parkinson's patients.","whyItMatters":"This was one of the first studies to directly show that genetic mutations linked to familial Parkinson's disease accelerate the physical clumping of alpha-synuclein into the fibrous deposits found in affected brain cells. It provided a mechanistic bridge between genetics and pathology, suggesting that speeding up protein aggregation may be how these mutations cause earlier disease onset.","specificNumbers":"","methodology":"in-vitro protein folding and aggregation assays with recombinant wild-type and mutant alpha-synuclein; circular dichroism spectroscopy, atomic force microscopy, and electron microscopy","limitations":"In vitro study using purified recombinant protein — does not account for the complex cellular environment, other Lewy body components, or in vivo conditions. No quantitative kinetic rate constants reported. Limited to two known familial mutations."},{"rthcId":"RPEP-00459","title":"Endogenous opioid peptides and mental stress in congestive heart failure patients.","authors":"Fontana, F; Bernardi, P; Pich, E M; Boschi, S; De Iasio, R; Spampinato, S","year":1998,"journal":"Peptides, 19(1), 21-6","doi":null,"pmid":"9437733","tags":["opioid-peptides","cardiovascular"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"NYHA class III heart failure patients had elevated resting beta-endorphin and neurohormone levels, with naloxone-modifiable stress responses, confirming active opioid system involvement in cardiovascular stress regulation.","whyItMatters":"This demonstrates that the endogenous opioid system is actively engaged in heart failure — not just passively elevated — and that blocking it with naloxone alters cardiovascular stress responses. This has implications for understanding both the adaptive and potentially maladaptive roles of opioid peptides in severe heart disease.","specificNumbers":"","methodology":"Clinical study of two groups of acute CHF patients (n=10 each) undergoing mental arithmetic stress tests with placebo or naloxone, measuring multiple neurohormones and opioid peptides.","limitations":"Small sample sizes (n=10 per group). Acute CHF patients — results may differ in chronic stable heart failure. Cross-sectional design limits causal interpretation."},{"rthcId":"RPEP-00460","title":"Opioid peptides in response to mental stress in asymptomatic dilated cardiomyopathy.","authors":"Fontana, F; Bernardi, P; Merlo Pich, E; Tartuferi, L; Boschi, S; De Iasio, R; Spampinato, S","year":1998,"journal":"Peptides, 19(7), 1147-53","doi":null,"pmid":"9786163","tags":["opioid-peptides","cardiovascular","anxiety-mood"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"Asymptomatic dilated cardiomyopathy patients had normal resting opioid peptide levels but showed altered opioid peptide responses to mental stress, alongside elevated ANF levels.","whyItMatters":"Understanding how the endogenous opioid system responds to stress in early heart disease could reveal biomarkers for disease progression and identify a role for opioid peptides in cardiovascular stress adaptation.","specificNumbers":"","methodology":"Clinical study of 14 asymptomatic dilated cardiomyopathy patients undergoing mental arithmetic stress tests with placebo vs. naloxone, measuring plasma beta-endorphin, met-enkephalin, dynorphin B, norepinephrine, endothelin-1, and ANF.","limitations":"Small sample size (n=14). Only asymptomatic patients studied — may not generalize to symptomatic heart failure. Cross-sectional design doesn't establish causality."},{"rthcId":"RPEP-00461","title":"Growth hormone secretagogues: mechanism of action and use in aging.","authors":"Fuh, V L; Bach, M A","year":1998,"journal":"Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society, 8(1), 13-20","doi":null,"pmid":"10990440","tags":["ghrp","mk-677","anti-aging","hormone-optimization"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"GH secretagogues function as somatostatin antagonists at the hypothalamic-pituitary level and can restore youthful GH secretion patterns in elderly subjects.","whyItMatters":"Age-related GH decline contributes to loss of muscle mass, bone density, and vitality. GH secretagogues offer a way to restore the body's own GH production rather than replacing it with injections, potentially maintaining more natural regulatory controls.","specificNumbers":"","methodology":"Review article synthesizing mechanistic studies and clinical trial data on GH secretagogues in aging populations.","limitations":"Review from 1998 — long-term safety data for GH secretagogues in aging were not yet available. GH restoration doesn't necessarily translate to clinically meaningful anti-aging outcomes. Potential risks of sustained GH elevation in elderly not fully characterized."},{"rthcId":"RPEP-00462","title":"Orally active growth hormone secretagogues: state of the art and clinical perspectives.","authors":"Ghigo, E; Arvat, E; Camanni, F","year":1998,"journal":"Annals of medicine, 30(2), 159-68","doi":null,"pmid":"9667794","tags":["ghrp","mk-677","hormone-optimization","clinical-trials"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Oral GH secretagogues effectively increase GH and IGF-1 through a specific receptor, with clinical potential spanning GH deficiency, aging, and catabolic states, though their optimal therapeutic role remained to be defined.","whyItMatters":"This review represented the most complete clinical assessment of oral GH secretagogues available at the time, helping define where these agents fit in endocrine therapeutics and identifying which clinical applications showed the most promise.","specificNumbers":"","methodology":"Comprehensive review of published preclinical and clinical data on oral GH secretagogues.","limitations":"1998 review — clinical trial database was still developing. Long-term outcome data not available. The therapeutic niche for oral GH secretagogues versus GH replacement was not yet resolved."},{"rthcId":"RPEP-00463","title":"The conformation of peptide thymosin alpha 1 in solution and in a membrane-like environment by circular dichroism and NMR spectroscopy. A possible model for its interaction with the lymphocyte membrane.","authors":"Grottesi, A; Sette, M; Palamara, T; Rotilio, G; Garaci, E; Paci, M","year":1998,"journal":"Peptides, 19(10), 1731-8","doi":null,"pmid":"9880079","tags":["thymosin-alpha-1","peptide-design","immune-function"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Thymosin alpha-1 adopts a structured conformation with a beta-turn (residues 5-8) and alpha helix (residues 17-24) in membrane-like environments, suggesting this shape change is required for immune cell activation.","whyItMatters":"Understanding the structural basis of how thymosin alpha-1 interacts with immune cells could guide the design of more effective peptide analogs for immunotherapy applications.","specificNumbers":"","methodology":"In-vitro structural biology study using circular dichroism and 2D NMR spectroscopy to analyze thymosin alpha-1 in water, phospholipid vesicles, SDS micelles, trifluoroethanol solution, and zinc ions.","limitations":"In-vitro study using model membranes that may not perfectly replicate real lymphocyte surfaces. The proposed interaction model is hypothetical and not confirmed by cell-based experiments."},{"rthcId":"RPEP-00464","title":"Loss of bombesin-induced feeding suppression in gastrin-releasing peptide receptor-deficient mice.","authors":"Hampton, L L; Ladenheim, E E; Akeson, M; Way, J M; Weber, H C; Sutliff, V E; Jensen, R T; Wine, L J; Arnheiter, H; Battey, J F","year":1998,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 95(6), 3188-92","doi":null,"pmid":"9501238","tags":["neuropeptides","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"GRP-R knockout mice completely lost bombesin-induced feeding suppression, demonstrating that GRP-R is the key receptor mediating this satiety signal.","whyItMatters":"Identifying GRP-R as the specific receptor for bombesin's appetite suppression opens the door to developing targeted peptide-based treatments for obesity and eating disorders.","specificNumbers":"","methodology":"Animal study using GRP-R gene knockout mice. Feeding behavior was measured after bombesin administration and compared between knockout and wild-type controls.","limitations":"Animal study in mice; results may not directly translate to humans. Knockout models eliminate the receptor entirely, which is more extreme than pharmacological modulation."},{"rthcId":"RPEP-00465","title":"A novel pentadecapeptide, BPC 157, blocks the stereotypy produced acutely by amphetamine and the development of haloperidol-induced supersensitivity to amphetamine.","authors":"Jelovac, N; Sikirić, P; Rucman, R; Petek, M; Perović, D; Konjevoda, P; Marović, A; Seiwerth, S; Grabarević, Z; Sumajstorcić, J; Dodig, G; Perić, J","year":1998,"journal":"Biological psychiatry, 43(7), 511-9","doi":null,"pmid":"9547930","tags":["bpc-157","neuroprotection","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"BPC-157 blocked acute amphetamine-induced stereotypy and prevented haloperidol-induced dopamine supersensitivity to amphetamine, without affecting normal baseline behavior.","whyItMatters":"BPC-157's ability to normalize disrupted dopamine signaling without sedating effects suggests it could have potential in treating conditions involving dopamine dysregulation, such as substance abuse or movement disorders.","specificNumbers":"","methodology":"Animal study in rats. BPC-157 was administered alongside amphetamine to measure acute effects on stereotypy, and during chronic haloperidol treatment to assess prevention of dopamine receptor supersensitivity.","limitations":"Animal study only. The exact mechanism by which BPC-157 interacts with the dopamine system was not determined. Doses and clinical translation to humans remain unknown."},{"rthcId":"RPEP-00466","title":"Pharmacokinetic evaluation of ipamorelin and other peptidyl growth hormone secretagogues with emphasis on nasal absorption.","authors":"Johansen, P B; Hansen, K T; Andersen, J V; Johansen, N L","year":1998,"journal":"Xenobiotica; the fate of foreign compounds in biological systems, 28(11), 1083-92","doi":null,"pmid":"9879640","tags":["ipamorelin","ghrp","bioavailability"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Ipamorelin demonstrated approximately 20% nasal bioavailability in rats, superior to GHRP-2, GHRP-6, and two other peptides, supporting its potential for non-invasive nasal delivery.","whyItMatters":"Most peptide therapies require injections, which limits their practical use. Finding that ipamorelin absorbs well through the nasal route could make growth hormone-releasing peptide therapy more accessible and convenient.","specificNumbers":"","methodology":"Animal pharmacokinetic study in male rats. Five peptidyl GH secretagogues were compared following IV, subcutaneous, oral, and nasal administration. Plasma levels were measured to calculate bioavailability.","limitations":"Rat pharmacokinetics may not directly predict human absorption. Nasal bioavailability can vary significantly between species. Long-term nasal tolerability was not assessed."},{"rthcId":"RPEP-00467","title":"Glucose stimulation of pancreatic beta-cell lines induces expression and secretion of dynorphin.","authors":"Josefsen, K; Buschard, K; Sørensen, L R; Wøllike, M; Ekman, R; Birkenbach, M","year":1998,"journal":"Endocrinology, 139(10), 4329-36","doi":null,"pmid":"9751516","tags":["opioid-peptides","diabetes"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Glucose stimulation induced prodynorphin gene expression in pancreatic beta-cell lines, with dynorphin peptides being processed and secreted, suggesting a novel opioid-mediated feedback mechanism in glucose regulation.","whyItMatters":"The discovery that beta-cells produce opioid peptides in response to glucose reveals a previously unknown layer of blood sugar regulation that could have implications for understanding diabetes and developing new treatments.","specificNumbers":"","methodology":"In-vitro study using subtraction cloning to identify glucose-induced genes in pancreatic beta-cell lines. Dynorphin expression and secretion were confirmed with immunoassays and molecular analysis.","limitations":"In-vitro study using cell lines, not intact pancreatic tissue. The functional role of secreted dynorphin was not determined. Cell line behavior may differ from normal beta-cells."},{"rthcId":"RPEP-00468","title":"Release of aqueous contents from phospholipid vesicles induced by cecropin A (1-8)-magainin 2 (1-12) hybrid and its analogues.","authors":"Kang, J H; Shin, S Y; Jang, S Y; Lee, M K; Hahm, K S","year":1998,"journal":"The journal of peptide research : official journal of the American Peptide Society, 52(1), 45-50","doi":null,"pmid":"9716250","tags":["antimicrobial-peptides","cancer","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"The cecropin A-magainin 2 hybrid peptide disrupts membranes via a two-step mechanism, and leucine substitution analogs showed enhanced membrane disruption and antitumor activity with preserved low hemolytic toxicity.","whyItMatters":"Antimicrobial peptides that selectively kill cancer cells while sparing normal cells are highly sought after. Understanding exactly how these peptides disrupt membranes enables rational design of more potent and safer analogs.","specificNumbers":"","methodology":"In-vitro study measuring fluorescent probe release from phospholipid vesicles to assess membrane disruption kinetics. Multiple peptide analogs were tested and compared for membrane activity.","limitations":"In-vitro study using artificial vesicles, not live cells. Membrane disruption in model systems may not perfectly predict activity against real bacterial or cancer cell membranes."},{"rthcId":"RPEP-00469","title":"New GH secretagogues and potential usefulness in thalassemia.","authors":"Karydis, I; Tolis, A; Tolis, G","year":1998,"journal":"Journal of pediatric endocrinology & metabolism : JPEM, 11 Suppl 3, 857-62","doi":null,"pmid":"10091157","tags":["ghrp","hormone-optimization","clinical-trials"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"GH secretagogues like GHRP-6 and hexarelin can stimulate growth hormone release through mechanisms distinct from GHRH, making them potentially useful for thalassemia patients with iron-damaged pituitary glands.","whyItMatters":"Thalassemia patients often develop GH deficiency from iron overload, leading to short stature and metabolic problems. GH secretagogues could offer a targeted treatment that works even when the normal GH-releasing pathway is damaged.","specificNumbers":"","methodology":"Review article summarizing the clinical potential of GH secretagogues in thalassemia, covering mechanism of action, clinical data, and rationale for use in this patient population.","limitations":"Review article with preliminary clinical data. Large-scale clinical trials in thalassemia patients had not been conducted at time of publication. Long-term safety with iron overload unknown."},{"rthcId":"RPEP-00470","title":"Potent suppression of HIV-1 replication in humans by T-20, a peptide inhibitor of gp41-mediated virus entry.","authors":"Kilby, J M; Hopkins, S; Venetta, T M; DiMassimo, B; Cloud, G A; Lee, J Y; Alldredge, L; Hunter, E; Lambert, D; Bolognesi, D; Matthews, T; Johnson, M R; Nowak, M A; Shaw, G M; Saag, M S","year":1998,"journal":"Nature medicine, 4(11), 1302-7","doi":null,"pmid":"9809555","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00471","title":"An experimental study of cardiac natriuretic peptides as markers of development of congestive heart failure.","authors":"Klinge, R; Hystad, M; Kjekshus, J; Karlberg, B E; Djøseland, O; Aakvaag, A; Hall, C","year":1998,"journal":"Scandinavian journal of clinical and laboratory investigation, 58(8), 683-91","doi":null,"pmid":"10088206","tags":["natriuretic-peptides","cardiovascular"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"BNP showed the most dramatic increase in ventricular tissue during heart failure progression and correlated most strongly with cardiac dysfunction severity, supporting its use as a heart failure biomarker.","whyItMatters":"BNP blood tests are now standard for diagnosing heart failure, and this study was part of the foundational research establishing why BNP is superior to other natriuretic peptides as a cardiac biomarker.","specificNumbers":"","methodology":"Animal study creating experimental chronic heart failure in rats. ANP and BNP were measured in atrial tissue, ventricular tissue, and plasma at different stages of heart failure progression using immunoassays.","limitations":"Animal model study in rats, which may not perfectly replicate human heart failure progression. The specific heart failure model used may not represent all types of cardiac dysfunction."},{"rthcId":"RPEP-00472","title":"Bactericidal domain of lactoferrin: detection, quantitation, and characterization of lactoferricin in serum by SELDI affinity mass spectrometry.","authors":"Kuwata, H; Yip, T T; Yip, C L; Tomita, M; Hutchens, T W","year":1998,"journal":"Biochemical and biophysical research communications, 245(3), 764-73","doi":null,"pmid":"9588189","tags":["antimicrobial-peptides","bioavailability","immune-function"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Lactoferricin was detected and quantified in human serum for the first time using SELDI affinity mass spectrometry, establishing its natural occurrence in the bloodstream.","whyItMatters":"Proving lactoferricin exists naturally in human blood transforms it from a lab curiosity to a confirmed part of the body's immune defense system, supporting research into boosting its levels through lactoferrin supplementation.","specificNumbers":"","methodology":"In-vitro analytical study developing SELDI affinity mass spectrometry to detect lactoferricin (3196 Da) in human serum. Used antibody-based capture combined with mass spectrometric identification.","limitations":"Method development study focused on detection capability rather than clinical outcomes. The functional significance of circulating lactoferricin levels was not assessed. Serum concentrations may vary significantly between individuals."},{"rthcId":"RPEP-00473","title":"Direct detection and quantitative determination of bovine lactoferricin and lactoferrin fragments in human gastric contents by affinity mass spectrometry.","authors":"Kuwata, H; Yip, T T; Yip, C L; Tomita, M; Hutchens, T W","year":1998,"journal":"Advances in experimental medicine and biology, 443, 23-32","doi":null,"pmid":"9781339","tags":["antimicrobial-peptides","bioavailability"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Affinity mass spectrometry enabled direct detection and quantification of lactoferricin and multiple lactoferrin-derived peptide fragments in human gastric contents, revealing the peptide generation process in detail.","whyItMatters":"This analytical tool allows researchers to precisely track how dietary proteins are broken down into bioactive peptides in the gut, which is essential for understanding bioavailability and designing effective oral peptide supplements.","specificNumbers":"","methodology":"Method development study using affinity-based mass spectrometry (BIA-MS) to capture and analyze lactoferrin-derived peptides from human gastric samples collected after oral lactoferrin ingestion.","limitations":"Method-focused study with limited clinical scope. The functional antimicrobial activity of detected fragments was not tested. Conditions in the study may not represent all digestive states."},{"rthcId":"RPEP-00474","title":"Direct evidence of the generation in human stomach of an antimicrobial peptide domain (lactoferricin) from ingested lactoferrin.","authors":"Kuwata, H; Yip, T T; Tomita, M; Hutchens, T W","year":1998,"journal":"Biochimica et biophysica acta, 1429(1), 129-41","doi":null,"pmid":"9920391","tags":["antimicrobial-peptides","bioavailability","infection"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"Direct detection of lactoferricin generation in the human stomach after oral lactoferrin ingestion, providing the first in-vivo evidence of this bioactive peptide's natural formation during digestion.","whyItMatters":"This proves that simply consuming lactoferrin-rich foods or supplements can generate antimicrobial peptides in the gut, providing a natural defense mechanism against pathogens and supporting the rationale for lactoferrin supplementation.","specificNumbers":"","methodology":"Clinical study in healthy human volunteers. Bovine lactoferrin was administered orally, and gastric contents were analyzed using surface-enhanced laser desorption/ionization mass spectrometry (SELDI-MS) and affinity techniques.","limitations":"Small clinical study focused on detection rather than quantifying antimicrobial activity. The amount of lactoferricin generated and its functional significance in preventing infections were not assessed."},{"rthcId":"RPEP-00475","title":"Properties of mu 3 opiate alkaloid receptors in macrophages, astrocytes, and HL-60 human promyelocytic leukemia cells.","authors":"Makman, M H; Dobrenis, K; Surratt, C K","year":1998,"journal":"Advances in experimental medicine and biology, 437, 137-48","doi":null,"pmid":"9666265","tags":["opioid-peptides","immune-function","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"The mu3 receptor on immune cells selectively binds opiate alkaloids (not endogenous opioid peptides), triggers nitric oxide release via constitutive nitric oxide synthase, and is present on macrophages, astrocytes, and leukemia cells.","whyItMatters":"Understanding how opioid receptors on immune cells work is crucial for managing the immunosuppressive effects of opioid medications and could reveal new therapeutic targets for immune modulation.","specificNumbers":"","methodology":"In-vitro binding studies and functional assays on macrophages, astrocytes, and HL-60 leukemia cells to characterize mu3 receptor properties, selectivity, and signaling pathways.","limitations":"In-vitro study using cell lines and cultured cells. The mu3 receptor's role in whole-organism immune function was not assessed. Relevance to in-vivo immune suppression by opioids needs confirmation."},{"rthcId":"RPEP-00476","title":"Biochemical detection of left-ventricular systolic dysfunction.","authors":"McDonagh, T A; Robb, S D; Murdoch, D R; Morton, J J; Ford, I; Morrison, C E; Tunstall-Pedoe, H; McMurray, J J; Dargie, H J","year":1998,"journal":"Lancet (London, England), 351(9095), 9-13","doi":null,"pmid":"9433422","tags":["natriuretic-peptides","cardiovascular"],"studyType":"cross-sectional","evidenceStrength":"strong","keyFinding":"Plasma BNP was superior to NT-ANP for detecting left ventricular systolic dysfunction in a general population, with particularly high sensitivity for moderate-to-severe cases.","whyItMatters":"Many people have undiagnosed heart dysfunction that leads to heart failure. A reliable blood test that can screen for this condition could enable earlier treatment and save lives. This study helped establish BNP as that screening tool.","specificNumbers":"","methodology":"Cross-sectional population study comparing plasma BNP and NT-ANP levels against echocardiographic assessment of left ventricular function. Control group was confirmed free of cardiac disorders to avoid bias from previous studies.","limitations":"Cross-sectional design cannot establish causal relationships. Sensitivity was lower for mild dysfunction. Specific cutoff values may vary between populations and assay methods."},{"rthcId":"RPEP-00477","title":"How does treatment influence endocrine mechanisms in acute severe heart failure? Effects on cardiac natriuretic peptides, the renin system, neuropeptide Y and catecholamines.","authors":"Missouris, C G; Grouzmann, E; Buckley, M G; Barron, J; MacGregor, G A; Singer, D R","year":1998,"journal":"Clinical science (London, England : 1979), 94(6), 591-9","doi":null,"pmid":"9854456","tags":["natriuretic-peptides","cardiovascular","neuropeptides"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"Treatment of acute severe heart failure reduced BNP and ANP levels but not catecholamines or renin-angiotensin activity, indicating natriuretic peptides more accurately reflect clinical improvement.","whyItMatters":"Knowing which hormones respond to treatment helps clinicians choose the best biomarkers to monitor therapy. The finding that BNP tracks treatment response while catecholamines don't has practical implications for patient monitoring.","specificNumbers":"","methodology":"Clinical observational study in 9 hospitalized patients with NYHA class IV heart failure. BNP, ANP, neuropeptide Y, catecholamines, and renin system hormones were measured before and after standard treatment.","limitations":"Very small sample size (9 patients). Observational design without control group. Treatment was not standardized. Results may not generalize to less severe heart failure."},{"rthcId":"RPEP-00478","title":"Interferon and thymosin combination therapy in naive patients with chronic hepatitis C: preliminary results.","authors":"Moscarella, S; Buzzelli, G; Romanelli, R G; Monti, M; Giannini, C; Careccia, G; Marrocchi, E M; Zignego, A L","year":1998,"journal":"Liver, 18(5), 366-9","doi":null,"pmid":"9831367","tags":["thymosin-alpha-1","immune-function","clinical-trials"],"studyType":"RCT","evidenceStrength":"moderate","keyFinding":"Thymosin alpha-1 (1 mg twice weekly) combined with interferon-alpha-2b (3 MU three times weekly) produced superior biochemical and virological responses compared to interferon alone in treatment-naive chronic hepatitis C patients.","whyItMatters":"Hepatitis C was a major global health burden in 1998. Finding that thymosin alpha-1 could enhance interferon therapy offered a way to improve cure rates for a disease that was difficult to treat at the time.","specificNumbers":"","methodology":"Randomized controlled trial comparing IFN-alpha-2b + thymosin alpha-1 (n=17) versus IFN-alpha-2b alone (n=17) in treatment-naive chronic hepatitis C patients. Assessed biochemical (ALT normalization) and virological (HCV RNA) response.","limitations":"Small sample size (17 per group). Preliminary results without long-term follow-up. The hepatitis C treatment landscape has changed dramatically since this study."},{"rthcId":"RPEP-00479","title":"Specific receptors for synthetic GH secretagogues in the human brain and pituitary gland.","authors":"Muccioli, G; Ghè, C; Ghigo, M C; Papotti, M; Arvat, E; Boghen, M F; Nilsson, M H; Deghenghi, R; Ong, H; Ghigo, E","year":1998,"journal":"The Journal of endocrinology, 157(1), 99-106","doi":null,"pmid":"9614363","tags":["ghrp","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Specific, high-affinity binding sites for GH secretagogues were identified in the human pituitary and multiple brain regions including hypothalamus and hippocampus, indicating CNS effects beyond GH release.","whyItMatters":"Finding GH secretagogue receptors throughout the brain suggests these peptides do more than just boost growth hormone. They may influence memory, appetite, sleep, and other neurological functions, expanding their potential therapeutic applications.","specificNumbers":"","methodology":"In-vitro binding study using radioiodinated Tyr-Ala-hexarelin on membrane preparations from human pituitary gland and various brain regions. Binding affinity and specificity were characterized.","limitations":"In-vitro binding study on tissue membranes. Cannot determine functional effects of receptor activation in different brain regions. Post-mortem tissue may not perfectly represent in-vivo receptor distribution."},{"rthcId":"RPEP-00480","title":"MK-677, an orally active growth hormone secretagogue, reverses diet-induced catabolism.","authors":"Murphy, M G; Plunkett, L M; Gertz, B J; He, W; Wittreich, J; Polvino, W M; Clemmons, D R","year":1998,"journal":"The Journal of clinical endocrinology and metabolism, 83(2), 320-5","doi":null,"pmid":"9467534","tags":["mk-677","hormone-optimization","muscle-recovery","clinical-trials"],"studyType":"RCT","evidenceStrength":"strong","keyFinding":"MK-677 at 25 mg daily reversed diet-induced nitrogen wasting in healthy volunteers, increasing IGF-1 by 40% and producing sustained anabolic effects comparable to GH injections.","whyItMatters":"Muscle wasting from illness, aging, or calorie restriction is a major health problem. An oral medication that prevents protein loss could help hospitalized patients, the elderly, and anyone recovering from illness maintain muscle mass.","specificNumbers":"","methodology":"Double-blind, randomized, placebo-controlled, two-period crossover study in 8 healthy volunteers (ages 24-39). Calorie restriction was used to induce negative nitrogen balance, then MK-677 or placebo was administered. Nitrogen balance, GH, IGF-1, and cortisol were measured.","limitations":"Small sample size (8 volunteers). Short-term study in healthy young adults. Effects in actual catabolic patients (elderly, critically ill) may differ. Long-term safety not assessed."},{"rthcId":"RPEP-00481","title":"Binding sites for growth hormone-releasing peptide.","authors":"Ong, H; Bodart, V; McNicoll, N; Lamontagne, D; Bouchard, J F","year":1998,"journal":"Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society, 8 Suppl B, 137-40","doi":null,"pmid":"10990149","tags":["ghrp","cardiovascular","receptor-signaling"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Multiple GHRP receptor subtypes exist in the pituitary, brain, and heart, with hexarelin binding cardiac tissue — explaining the cardiovascular effects of GH secretagogues beyond their GH-releasing activity.","whyItMatters":"Understanding that GHRPs work through multiple receptor subtypes in different tissues helps explain their diverse effects and could lead to more targeted peptide therapies for specific conditions like heart disease or neurological disorders.","specificNumbers":"","methodology":"Review article synthesizing binding studies, second messenger analyses, and tissue distribution data for GHRP receptors across the hypothalamic-pituitary system, brain, and heart.","limitations":"Review of preliminary findings from multiple studies. Receptor subtype classification was still evolving. Some binding data was from animal tissues with uncertain human relevance."},{"rthcId":"RPEP-00482","title":"Identification of a pituitary growth hormone-releasing peptide (GHRP) receptor subtype by photoaffinity labeling.","authors":"Ong, H; McNicoll, N; Escher, E; Collu, R; Deghenghi, R; Locatelli, V; Ghigo, E; Muccioli, G; Boghen, M; Nilsson, M","year":1998,"journal":"Endocrinology, 139(1), 432-5","doi":null,"pmid":"9421445","tags":["ghrp","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Photoaffinity labeling with modified hexarelin identified a specific GHRP receptor protein in pituitary membranes, confirming the existence of a distinct GH secretagogue receptor subtype.","whyItMatters":"Physically identifying the GHRP receptor protein was essential for eventually cloning it, which led to the discovery of ghrelin and the broader understanding of how these peptides work in the body.","specificNumbers":"","methodology":"In-vitro receptor identification study using photoaffinity labeling with a benzophenone-modified hexarelin analog on rat and human pituitary membranes. SDS-PAGE and autoradiography were used to identify labeled proteins.","limitations":"Technical receptor identification study. Photoaffinity labeling can produce artifacts. The functional significance of the identified protein was not established in this study alone."},{"rthcId":"RPEP-00483","title":"Life without neuropeptide Y.","authors":"Palmiter, R D; Erickson, J C; Hollopeter, G; Baraban, S C; Schwartz, M W","year":1998,"journal":"Recent progress in hormone research, 53, 163-99","doi":null,"pmid":"9769708","tags":["neuropeptides","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"NPY knockout mice had normal appetite and body weight but showed dramatically increased susceptibility to seizures and excitotoxicity, revealing NPY's primary role as an endogenous anticonvulsant.","whyItMatters":"Identifying NPY as a critical anticonvulsant opens new therapeutic avenues for epilepsy. The finding that appetite was unaffected also challenges simplistic views of NPY as a hunger hormone, suggesting redundancy in appetite regulation.","specificNumbers":"","methodology":"Animal study using NPY gene-inactivated mice. Feeding behavior, body weight, seizure susceptibility, and excitotoxicity were assessed and compared to wild-type controls.","limitations":"Knockout models eliminate the gene entirely from development, which may trigger compensatory mechanisms. Results in mice may not fully translate to humans. The normal appetite finding may reflect developmental compensation."},{"rthcId":"RPEP-00484","title":"High doses of thymosin alpha 1 enhance the anti-tumor efficacy of combination chemo-immunotherapy for murine B16 melanoma.","authors":"Pica, F; Fraschetti, M; Matteucci, C; Tuthill, C; Rasi, G","year":1998,"journal":"Anticancer research, 18(5A), 3571-8","doi":null,"pmid":"9858941","tags":["thymosin-alpha-1","cancer","immune-function"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Dose-escalation of thymosin alpha-1 in triple chemo-immunotherapy (cyclophosphamide + thymosin alpha-1 + interferon) produced dose-dependent increases in anti-tumor efficacy against B16 melanoma in mice.","whyItMatters":"Showing that thymosin alpha-1 has dose-dependent anti-tumor effects suggests the immune-boosting benefits increase with higher doses, which is important for optimizing cancer immunotherapy combinations.","specificNumbers":"","methodology":"Animal study in C57BL/6 mice with B16 melanoma. Multiple thymosin alpha-1 doses were tested in combination with cyclophosphamide and low-dose interferon-alpha/beta. Tumor growth and immune cell activity were measured.","limitations":"Mouse melanoma model; results may not translate directly to human cancer. B16 is a specific melanoma model and results may vary with other cancer types. Toxicity of higher doses not extensively characterized."},{"rthcId":"RPEP-00485","title":"Ipamorelin, the first selective growth hormone secretagogue.","authors":"Raun, K; Hansen, B S; Johansen, N L; Thøgersen, H; Madsen, K; Ankersen, M; Andersen, P H","year":1998,"journal":"European journal of endocrinology, 139(5), 552-61","doi":null,"pmid":"9849822","tags":["ipamorelin","hormone-optimization","clinical-trials"],"studyType":"clinical-trial","evidenceStrength":"strong","keyFinding":"Ipamorelin released GH with potency similar to GHRP-6 but did not increase ACTH, cortisol, prolactin, or FSH even at doses 200-fold higher than effective GH-releasing doses, making it the first truly selective GH secretagogue.","whyItMatters":"Older GH-releasing peptides boosted cortisol and prolactin along with GH, limiting their therapeutic use. Ipamorelin's selectivity means it could stimulate growth hormone without these unwanted hormonal side effects.","specificNumbers":"","methodology":"Clinical pharmacology study describing ipamorelin's development from a chemistry program. Tested in vitro and in vivo including human subjects. GH, cortisol, ACTH, prolactin, and other hormones measured after various doses.","limitations":"Clinical data available at time of publication was limited. Long-term safety and efficacy studies were not yet completed. Selectivity in healthy volunteers may differ from patient populations."},{"rthcId":"RPEP-00486","title":"Plasma N-terminal pro-brain natriuretic peptide and adrenomedullin: new neurohormonal predictors of left ventricular function and prognosis after myocardial infarction.","authors":"Richards, A M; Nicholls, M G; Yandle, T G; Frampton, C; Espiner, E A; Turner, J G; Buttimore, R C; Lainchbury, J G; Elliott, J M; Ikram, H; Crozier, I G; Smyth, D W","year":1998,"journal":"Circulation, 97(19), 1921-9","doi":null,"pmid":"9609085","tags":["natriuretic-peptides","cardiovascular"],"studyType":"cohort","evidenceStrength":"strong","keyFinding":"NT-proBNP at 2-4 days post-MI correlated strongly with LVEF (r=-0.63) and was the strongest independent predictor of mortality. NT-proBNP ≥160 pmol/L identified high-risk patients. Adrenomedullin also predicted poor prognosis.","whyItMatters":"Identifying which patients are at highest risk after a heart attack allows targeted intensive treatment. Simple blood tests that predict outcomes better than existing markers can save lives through better risk stratification.","specificNumbers":"","methodology":"Prospective cohort study in 121 myocardial infarction patients. NT-proBNP, adrenomedullin, and established neurohormonal markers were measured at 2-4 days. LVEF was assessed by radionuclide scanning. Patients were followed for mortality outcomes.","limitations":"Single-center cohort study. Specific follow-up duration and mortality rates not detailed in abstract excerpt. NT-proBNP cutoff values may vary between assays and populations."},{"rthcId":"RPEP-00487","title":"Dietary peptides improve wound healing following surgery.","authors":"Roberts, P R; Black, K W; Santamauro, J T; Zaloga, G P","year":1998,"journal":"Nutrition (Burbank, Los Angeles County, Calif.), 14(3), 266-9","doi":null,"pmid":"9583369","tags":[],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Peptide-based enteral diets significantly improved surgical wound healing compared to equivalent amino acid-based diets in rats. Wound bursting pressure — the gold standard measure of wound strength — was 30% higher in the peptide-fed group (179±9 vs. 138±12 mmHg, P=0.02).\n\nSpecifically, the dietary peptide carnosine (a dipeptide of beta-alanine and histidine) improved wound strength by 23% compared to a diet containing its constituent amino acids (143±10 vs. 116±8 mmHg, P=0.005). This demonstrates that peptides provide wound-healing benefits beyond what their individual amino acid components can deliver — peptides are not just pre-digested protein.","whyItMatters":"Hospital patients recovering from surgery are often fed through tubes with nutritional formulas. Most formulas use free amino acids rather than peptides because they're easier to manufacture. This study shows that's a mistake — peptides, especially carnosine, actively promote wound healing in a way that amino acids alone cannot. Since carnosine is absent from most enteral formulas, adding it could be a simple, low-cost way to improve surgical recovery.","specificNumbers":"n=38 rats total · Peptide vs. AA diet: 179±9 vs. 138±12 mmHg (P=0.02) · Carnosine vs. control: 143±10 vs. 116±8 mmHg (P=0.005) · 10-day feeding period · Tube feeding to small bowel","methodology":"Prospective randomized study in 38 male Sprague-Dawley rats. After standardized abdominal wounds, 20 rats were randomized to isonitrogenous (equal protein) peptide-based vs. amino acid-based diets for 10 days. An additional 18 rats were randomized to amino acid diets supplemented with either carnosine or its constituent amino acids. Diets were delivered via small bowel feeding tubes. Wound strength was measured as bursting pressure.","limitations":"This is a rat study and results may not directly translate to human surgical recovery. The sample sizes are small (20 in the first experiment, 18 in the second). Only one wound type (abdominal) and one time point (10 days) were tested. The abstract doesn't report on wound infection rates, collagen content, or other wound healing parameters beyond bursting pressure."},{"rthcId":"RPEP-00488","title":"Measurement and significance of circulating natriuretic peptides in cardiovascular disease.","authors":"Sagnella, G A","year":1998,"journal":"Clinical science (London, England : 1979), 95(5), 519-29","doi":null,"pmid":"9791037","tags":["natriuretic-peptides","cardiovascular"],"studyType":"review","evidenceStrength":"strong","keyFinding":"ANP and BNP are sensitive markers of cardiac volume and pressure overload with clinical utility in diagnosing heart failure, monitoring treatment, predicting prognosis, and screening for asymptomatic cardiac dysfunction.","whyItMatters":"This review synthesized the evidence that made natriuretic peptide testing a cornerstone of modern cardiology, influencing clinical guidelines that are still in use today.","specificNumbers":"","methodology":"Comprehensive review examining the physiology, measurement, and clinical applications of circulating ANP and BNP across cardiovascular diseases including heart failure, hypertension, and post-surgical monitoring.","limitations":"Review of the literature available through 1998. Assay standardization and optimal cutoff values were still being established. Some clinical applications were based on limited data."},{"rthcId":"RPEP-00489","title":"Beta-casomorphin-5 stimulates neurite outgrowth in a mouse neuroblastoma cell line (Neuro-2a).","authors":"Sakaguchi, M; Murayama, K; Yabe, K; Satoh, M; Takeuchi, M; Matsumura, E","year":1998,"journal":"Neuroscience letters, 251(2), 97-100","doi":null,"pmid":"9718983","tags":["opioid-peptides","neuroprotection","bioactive-food-peptides"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Beta-casomorphin-5 stimulated neurite outgrowth in Neuro-2a cells at picomolar concentrations via mu-opioid receptors, demonstrated by naloxone reversibility and DAMGO replication of the effect.","whyItMatters":"The finding that a milk-derived peptide promotes nerve growth suggests dietary proteins may influence nervous system development, particularly relevant to infant brain development during breastfeeding.","specificNumbers":"","methodology":"In-vitro study using mouse neuroblastoma (Neuro-2a) cell line. Beta-casomorphin-5, DAMGO, and naloxone were applied at various concentrations. Neurite outgrowth was quantified morphologically.","limitations":"In-vitro study using a cancer cell line (neuroblastoma), which may not reflect normal neuron behavior. Whether beta-casomorphin-5 reaches the brain after oral milk consumption is unclear. Picomolar activity in vitro may not translate to in-vivo effects."},{"rthcId":"RPEP-00490","title":"Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior.","authors":"Sakurai, T; Amemiya, A; Ishii, M; Matsuzaki, I; Chemelli, R M; Tanaka, H; Williams, S C; Richardson, J A; Kozlowski, G P; Wilson, S; Arch, J R; Buckingham, R E; Haynes, A C; Carr, S A; Annan, R S; McNulty, D E; Liu, W S; Terrett, J A; Elshourbagy, N A; Bergsma, D J; Yanagisawa, M","year":1998,"journal":"Cell, 92(4), 573-85","doi":null,"pmid":"9491897","tags":["orexin","neuropeptides"],"studyType":"original-research","evidenceStrength":"landmark","keyFinding":"This landmark study identified two entirely new neuropeptides — orexin-A and orexin-B — both produced from the same precursor protein in the hypothalamus. These peptides bind to and activate two closely related G protein-coupled receptors that had previously been \"orphan\" receptors (receptors with no known ligand).\n\nOrexin-A and orexin-B have no structural similarity to any previously known regulatory peptides, making them a completely novel peptide family. They are produced by neurons in and around the lateral and posterior hypothalamus of rat brains. When injected into the brain, both peptides stimulated food consumption. Furthermore, fasting caused an increase in prepro-orexin mRNA, indicating these peptides are part of the body's natural feedback system for regulating hunger and feeding behavior.","whyItMatters":"This is one of the most important neuropeptide discoveries of the late 20th century. Orexins (also called hypocretins) turned out to control not just appetite but also wakefulness, reward, and arousal. The loss of orexin-producing neurons was later found to cause narcolepsy. This single paper launched an entire field of research and led to the development of orexin receptor antagonist drugs like suvorexant (Belsomra) for insomnia. Published in Cell — one of the highest-impact journals in biology.","specificNumbers":"2 novel neuropeptides identified · 2 orphan GPCRs matched · Orexin-A and orexin-B from same precursor · Lateral/posterior hypothalamus localization · Fasting upregulates prepro-orexin mRNA","methodology":"The researchers used a combination of molecular biology techniques to identify orexin-A and orexin-B. They screened orphan G protein-coupled receptors, purified the peptides that activated them, identified their precursor gene, mapped where they were produced in the rat brain using mRNA localization and immunohistochemistry, and tested their effects on feeding behavior through central (brain) administration in rats.","limitations":"This initial discovery study was conducted entirely in rats, so direct translation to human physiology wasn't established here (though it was later confirmed). The study focused on feeding behavior and didn't explore the many other functions orexins were later found to have, including sleep/wake regulation. The mechanism by which orexins stimulate feeding was not fully elucidated in this paper."},{"rthcId":"RPEP-00491","title":"Proadrenomedullin-derived peptides.","authors":"Samson, W K","year":1998,"journal":"Frontiers in neuroendocrinology, 19(2), 100-27","doi":null,"pmid":"9578982","tags":["neuropeptides","cardiovascular"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Adrenomedullin and PAMP are co-produced from the same gene but lower blood pressure through distinct mechanisms (direct vascular vs. neural), and are expressed in diverse tissues with roles in cardiovascular, reproductive, and cancer biology.","whyItMatters":"These peptides represent a sophisticated blood pressure control system. Understanding their distinct mechanisms could lead to novel treatments for hypertension, heart failure, and potentially cancer.","specificNumbers":"","methodology":"Review article summarizing the biology, tissue distribution, cardiovascular effects, and clinical significance of adrenomedullin and PAMP, including their roles in pregnancy and cancer.","limitations":"Review based on early research; many proposed roles were not yet confirmed in clinical studies. The relative importance of AM vs. PAMP in human physiology was not fully established."},{"rthcId":"RPEP-00492","title":"The growth hormone secretagogue KP-102-induced stimulation of food intake is modified by fasting, restraint stress, and somatostatin in rats.","authors":"Shibasaki, T; Yamauchi, N; Takeuchi, K; Ishii, S; Sugihara, H; Wakabayashi, I","year":1998,"journal":"Neuroscience letters, 255(1), 9-12","doi":null,"pmid":"9839714","tags":["ghrp","neuropeptides"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"KP-102 stimulated food intake in freely-fed but not fasted or stressed rats, and central somatostatin administration blocked this effect, demonstrating state-dependent appetite modulation by GH secretagogues.","whyItMatters":"Understanding that GH peptides only stimulate appetite under certain conditions helps predict their effects in different patient populations and reveals how the brain integrates hunger signals with metabolic status.","specificNumbers":"","methodology":"Animal study in rats. KP-102-induced food intake was measured under normal feeding, 24-hour fasting, and post-restraint stress conditions. Somatostatin was administered intracerebroventricularly to test its blocking effect.","limitations":"Rat study with limited translational certainty to humans. Single stress model used. The mechanism by which fasting or stress blocks KP-102's appetite effect was not determined."},{"rthcId":"RPEP-00493","title":"Human fetal pituitary expresses functional growth hormone-releasing peptide receptors.","authors":"Shimon, I; Yan, X; Melmed, S","year":1998,"journal":"The Journal of clinical endocrinology and metabolism, 83(1), 174-8","doi":null,"pmid":"9435437","tags":["ghrp","hormone-optimization","fertility"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"GHRP receptor mRNA was detected in human fetal pituitary by RT-PCR, and GHRP-2 stimulated dose-dependent GH release from cultured fetal pituitary cells, demonstrating functional GH secretagogue receptors are present before birth.","whyItMatters":"Knowing the GH secretagogue system is active in fetal development suggests it plays a role in prenatal growth, which has implications for understanding growth disorders and the safety considerations of GH-releasing peptides in reproductive contexts.","specificNumbers":"","methodology":"In-vitro study using human fetal pituitary tissue. RT-PCR detected GHRP receptor mRNA expression. Cultured fetal pituitary cells were stimulated with GHRP-2 to demonstrate functional GH release.","limitations":"In-vitro study using isolated fetal tissue. Whether GHRP receptor activation plays a physiological role in fetal growth was not established. Limited fetal tissue availability restricts sample sizes."},{"rthcId":"RPEP-00494","title":"Characterization of immunoreactive dynorphin B and beta-endorphin in human plasma.","authors":"Silberring, J; Li, Y M; Terenius, L; Nylander, I","year":1998,"journal":"Peptides, 19(8), 1329-37","doi":null,"pmid":"9809646","tags":["opioid-peptides","bioavailability"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Dynorphin B and beta-endorphin were confirmed in human plasma by HPLC and mass spectrometry, while dynorphin A was undetectable due to rapid enzymatic conversion to leu-enkephalin in blood.","whyItMatters":"Understanding which opioid peptides are stable enough to circulate in blood versus those degraded immediately helps researchers choose the right biomarkers and design more stable peptide therapeutics.","specificNumbers":"","methodology":"In-vitro analytical study using radioimmunoassay, HPLC, and mass spectrometry to characterize opioid peptides in human plasma. Stability experiments tracked dynorphin A degradation in blood.","limitations":"In-vitro characterization study. Blood processing can affect peptide levels. Individual variation in peptide levels was not extensively characterized."},{"rthcId":"RPEP-00495","title":"Production of beta-defensins by human airway epithelia.","authors":"Singh, P K; Jia, H P; Wiles, K; Hesselberth, J; Liu, L; Conway, B A; Greenberg, E P; Valore, E V; Welsh, M J; Ganz, T; Tack, B F; McCray, P B","year":1998,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 95(25), 14961-6","doi":null,"pmid":"9843998","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00496","title":"Treatment with the oral growth hormone secretagogue MK-677 increases markers of bone formation and bone resorption in obese young males.","authors":"Svensson, J; Ohlsson, C; Jansson, J O; Murphy, G; Wyss, D; Krupa, D; Cerchio, K; Polvino, W; Gertz, B; Baylink, D; Mohan, S; Bengtsson, B A","year":1998,"journal":"Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 13(7), 1158-66","doi":null,"pmid":"9661080","tags":["mk-677","bone-joint","hormone-optimization","clinical-trials"],"studyType":"RCT","evidenceStrength":"moderate","keyFinding":"MK-677 (25 mg/day for 8 weeks) increased bone formation markers more than resorption markers in 24 obese young males, with elevated IGF-1 levels suggesting a growth hormone-mediated anabolic bone effect.","whyItMatters":"Bone loss is a major health concern in aging and obesity. An oral medication that increases bone formation could potentially prevent osteoporosis, and this study shows MK-677 activates bone-building processes.","specificNumbers":"","methodology":"Randomized, double-blind, placebo-controlled parallel study. 24 obese males (BMI >30, ages 19-49) received MK-677 25 mg/day or placebo for 8 weeks. Bone turnover markers, GH, and IGF-1 were measured.","limitations":"Short duration (8 weeks) — bone density changes take months to years to manifest. Markers indicate bone turnover direction but don't directly measure bone density. Obese young male population may not represent the groups most at risk for osteoporosis."},{"rthcId":"RPEP-00497","title":"Two-month treatment of obese subjects with the oral growth hormone (GH) secretagogue MK-677 increases GH secretion, fat-free mass, and energy expenditure.","authors":"Svensson, J; Lönn, L; Jansson, J O; Murphy, G; Wyss, D; Krupa, D; Cerchio, K; Polvino, W; Gertz, B; Boseaus, I; Sjöström, L; Bengtsson, B A","year":1998,"journal":"The Journal of clinical endocrinology and metabolism, 83(2), 362-9","doi":null,"pmid":"9467542","tags":["mk-677","weight-loss","hormone-optimization","clinical-trials"],"studyType":"RCT","evidenceStrength":"strong","keyFinding":"MK-677 (25 mg/day for 8 weeks) increased 24-hour GH secretion rate by 1.8-fold, normalized pulsatile GH profiles, increased fat-free mass by ~3 kg, and raised basal metabolic rate in obese males.","whyItMatters":"Obesity creates a vicious cycle: excess fat suppresses GH, which promotes more fat storage and muscle loss. An oral medication that breaks this cycle by restoring GH secretion could fundamentally change how obesity-related metabolic dysfunction is treated.","specificNumbers":"","methodology":"Randomized, double-blind, placebo-controlled parallel study. 24 obese males (BMI >30, ages 19-49) received MK-677 25 mg/day or placebo for 8 weeks. GH profiles (24-h sampling), body composition (DEXA), and energy expenditure measured.","limitations":"Small sample (24 men). Only 8 weeks duration. Body fat changes were not statistically significant despite favorable trends. All participants were male; effects in women unknown."},{"rthcId":"RPEP-00498","title":"Marked elevation of brain natriuretic peptide levels in pericardial fluid is closely associated with left ventricular dysfunction.","authors":"Tanaka, T; Hasegawa, K; Fujita, M; Tamaki, S I; Yamazato, A; Kihara, Y; Nohara, R; Sasayama, S","year":1998,"journal":"Journal of the American College of Cardiology, 31(2), 399-403","doi":null,"pmid":"9462585","tags":["natriuretic-peptides","cardiovascular"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"BNP concentrations in pericardial fluid were markedly elevated above plasma levels and closely associated with left ventricular dysfunction severity, supporting BNP's role as a local cardiac autocrine/paracrine factor.","whyItMatters":"This shows BNP isn't just a blood biomarker — it's a local cardiac signal that the heart uses to regulate its own function. This deepens understanding of how the heart responds to stress and failure.","specificNumbers":"","methodology":"Clinical study collecting pericardial fluid and blood samples during cardiac surgery. ANP and BNP were measured in both compartments and correlated with echocardiographic left ventricular function.","limitations":"Surgical patients may not represent all cardiac conditions. Pericardial fluid collection is only possible during surgery, limiting clinical applicability. Cross-sectional design."},{"rthcId":"RPEP-00499","title":"Electroacupuncture: mechanisms and clinical application.","authors":"Ulett, G A; Han, S; Han, J S","year":1998,"journal":"Biological psychiatry, 44(2), 129-38","doi":null,"pmid":"9646895","tags":["opioid-peptides","pain","neuropeptides"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Low-frequency (2 Hz) electroacupuncture activates endorphin/enkephalin systems (mu/delta receptors), while high-frequency (100 Hz) activates dynorphin systems (kappa receptors), with combined frequencies providing additive analgesia.","whyItMatters":"Providing a mechanistic explanation for acupuncture's pain relief through endogenous opioid peptides validates this ancient practice scientifically and opens the door to optimizing treatment protocols based on which opioid system is targeted.","specificNumbers":"","methodology":"Review of experimental studies examining opioid peptide release, receptor involvement, and analgesic effects of electroacupuncture at different frequencies in animals and humans.","limitations":"Review of primarily animal studies. The translation of specific frequency-peptide relationships to clinical pain conditions in humans requires further validation. Individual responses to acupuncture vary significantly."},{"rthcId":"RPEP-00500","title":"Leptin levels in protracted critical illness: effects of growth hormone-secretagogues and thyrotropin-releasing hormone.","authors":"Van den Berghe, G; Wouters, P; Carlsson, L; Baxter, R C; Bouillon, R; Bowers, C Y","year":1998,"journal":"The Journal of clinical endocrinology and metabolism, 83(9), 3062-70","doi":null,"pmid":"9745404","tags":["ghrp","hormone-optimization","clinical-trials"],"studyType":"RCT","evidenceStrength":"moderate","keyFinding":"GHRP-2 combined with TRH infusion reduced elevated leptin levels and reactivated suppressed GH and thyroid axes in prolonged critically ill patients, addressing the paradoxical fat-gain/muscle-wasting metabolic state.","whyItMatters":"Muscle wasting in ICU patients dramatically increases mortality and recovery time. Correcting the underlying hormonal dysfunction with peptide therapy could preserve muscle and improve survival in this vulnerable population.","specificNumbers":"","methodology":"Randomized controlled trial in prolonged critically ill ICU patients. Continuous IV infusions of GHRP-2, TRH, and their combination were tested. Leptin, GH, IGF-1, thyroid hormones, and metabolic markers measured.","limitations":"ICU patient population is heterogeneous. Short-term hormonal changes may not translate to improved clinical outcomes. Small study with inherent challenges of critical care research."},{"rthcId":"RPEP-00501","title":"Neuroendocrinology of prolonged critical illness: effects of exogenous thyrotropin-releasing hormone and its combination with growth hormone secretagogues.","authors":"Van den Berghe, G; de Zegher, F; Baxter, R C; Veldhuis, J D; Wouters, P; Schetz, M; Verwaest, C; Van der Vorst, E; Lauwers, P; Bouillon, R; Bowers, C Y","year":1998,"journal":"The Journal of clinical endocrinology and metabolism, 83(2), 309-19","doi":null,"pmid":"9467533","tags":["ghrp","hormone-optimization","clinical-trials"],"studyType":"RCT","evidenceStrength":"moderate","keyFinding":"Combined GHRP-2 and TRH infusion most effectively reactivated both pulsatile GH secretion and the thyrotropic axis in 20 prolonged critically ill patients, with effects exceeding either agent alone.","whyItMatters":"The hormonal suppression in critical illness is not just a consequence of being sick — it actively worsens outcomes by driving muscle loss and metabolic dysfunction. Correcting it with peptide therapy could improve survival.","specificNumbers":"","methodology":"Randomized trial in 20 adult critically ill patients. Continuous IV infusions of TRH, GHRP-2, GHRH alone and in combinations were administered. Pulsatile GH, TSH, thyroid hormones, and IGF-1 were measured over treatment periods.","limitations":"20 patients — small sample. Hormonal endpoints, not clinical outcomes. Heterogeneous ICU population. Continuous IV infusion is resource-intensive for routine clinical use."},{"rthcId":"RPEP-00502","title":"Presynaptic and postsynaptic actions and modulation of neuroendocrine neurons by a new hypothalamic peptide, hypocretin/orexin.","authors":"van den Pol, A N; Gao, X B; Obrietan, K; Kilduff, T S; Belousov, A B","year":1998,"journal":"The Journal of neuroscience : the official journal of the Society for Neuroscience, 18(19), 7962-71","doi":null,"pmid":"9742163","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00503","title":"The peptide orphanin FQ inhibits beta-endorphin neurons and neurosecretory cells in the hypothalamic arcuate nucleus by activating an inwardly-rectifying K+ conductance.","authors":"Wagner, E J; Rønnekleiv, O K; Grandy, D K; Kelly, M J","year":1998,"journal":"Neuroendocrinology, 67(2), 73-82","doi":null,"pmid":"9508037","tags":["opioid-peptides","neuropeptides","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Orphanin FQ inhibited 68% of arcuate nucleus neurons, including beta-endorphin cells and neurosecretory neurons, through activation of inwardly-rectifying potassium conductance, providing a cellular mechanism for its anti-opioid effects.","whyItMatters":"Understanding how orphanin FQ suppresses the brain's natural painkilling system helps explain pain conditions where the body's opioid defense fails, and could inform development of treatments that block this suppression.","specificNumbers":"","methodology":"Electrophysiology study in rat hypothalamic brain slices. Whole-cell and extracellular recordings measured OFQ effects on arcuate nucleus neurons. Pharmacological tools identified potassium channel involvement.","limitations":"Brain slice electrophysiology in rats; results may not fully translate to intact human brain. Acute application may not reflect chronic nociceptin signaling. The functional consequences for pain and hormone release were inferred, not directly demonstrated."},{"rthcId":"RPEP-00504","title":"Synthetic melanotropic peptide initiates erections in men with psychogenic erectile dysfunction: double-blind, placebo controlled crossover study.","authors":"Wessells, H; Fuciarelli, K; Hansen, J; Hadley, M E; Hruby, V J; Dorr, R; Levine, N","year":1998,"journal":"The Journal of urology, 160(2), 389-93","doi":null,"pmid":"9679884","tags":[],"studyType":"rct","evidenceStrength":"moderate","keyFinding":"Melanotan-II, a synthetic cyclic peptide analog of alpha-melanocyte-stimulating hormone (α-MSH), induced clinically apparent erections in 8 out of 10 men with psychogenic erectile dysfunction in a double-blind, placebo-controlled crossover trial.\n\nMen treated with Melanotan-II had an average of 38 minutes of tip rigidity above 80% — the threshold for penetrative intercourse — compared to just 3 minutes with placebo (p=0.0045). Side effects included nausea, yawning, stretching, and decreased appetite, but none required treatment.\n\nThe effective dose was 0.025 mg/kg administered subcutaneously.","whyItMatters":"This was one of the earliest controlled studies demonstrating that a peptide acting through the melanocortin system in the brain — rather than directly on blood vessels like Viagra — could trigger erections. It proved that sexual arousal could be initiated centrally through peptide signaling, opening an entirely new pathway for treating erectile dysfunction. This research ultimately contributed to the development of bremelanotide (Vyleesi), which was FDA-approved in 2019 for hypoactive sexual desire disorder.","specificNumbers":"n=10 · 8/10 achieved erections · Tip rigidity >80%: 38 min (MT-II) vs 3 min (placebo) · p=0.0045 · Dose: 0.025 mg/kg SC","methodology":"Double-blind, placebo-controlled crossover study with 10 men diagnosed with psychogenic erectile dysfunction (no organic cause). Each subject received both Melanotan-II (0.025 mg/kg) and placebo subcutaneously in randomized order. Erections were measured objectively using real-time RigiScan monitoring over a 6-hour period, recording presence, duration, and rigidity.","limitations":"Very small sample size (n=10). Only men with psychogenic (non-organic) erectile dysfunction were included, so results may not apply to men with vascular or neurogenic causes. The crossover design helps control for individual variation but the small numbers limit statistical power. Melanotan-II is not FDA-approved and has significant safety concerns beyond what this short study captured."},{"rthcId":"RPEP-00505","title":"Neurotrophic activities and therapeutic experience with a brain derived peptide preparation.","authors":"Windisch, M; Gschanes, A; Hutter-Paier, B","year":1998,"journal":"Journal of neural transmission. Supplementum, 53, 289-98","doi":null,"pmid":"9700665","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Cerebrolysin demonstrated dual neurotrophic and neuroprotective activity across multiple experimental models, promoting nerve cell growth in both peripheral and central nervous system neurons and protecting against various types of neuronal damage.\n\nIn clinical trials with Alzheimer's disease patients, Cerebrolysin produced rapid improvement in overall patient state, particularly cognitive performance. Most notably, these improvements were long-lasting — detectable even 6 months after stopping treatment. This persistence suggests the drug may induce actual repair processes rather than simply providing temporary symptomatic relief. The drug showed extremely high tolerability with no reports of serious side effects, a significant advantage over natural neurotrophic factors which cause problems like hyperalgesia and weight loss.","whyItMatters":"Natural neurotrophic factors have long been considered promising treatments for neurodegenerative diseases, but they've been stymied by the blood-brain barrier and side effects. Cerebrolysin represents an alternative strategy — using smaller peptide fragments that can potentially overcome these delivery challenges while retaining the beneficial biological activity. The finding that cognitive improvements persist months after treatment cessation is particularly significant, as it suggests disease-modifying rather than merely symptomatic effects.","specificNumbers":"","methodology":"This is a review paper summarizing preclinical and clinical research on Cerebrolysin. The preclinical work included in vitro and in vivo studies examining neurotrophic effects on different neuronal populations and neuroprotective properties after various types of lesions, with behavioral testing of learning and memory. Clinical evidence comes from trials in Alzheimer's disease patients assessing cognitive performance and overall clinical state, with follow-up periods extending to 6 months post-treatment.","limitations":"This is a narrative review, not a systematic review or meta-analysis, so there is potential for selective reporting. The clinical trial data described lacks specific patient numbers, effect sizes, or statistical analyses in the abstract. The review is authored by researchers associated with Cerebrolysin research, raising potential conflict of interest. The paper is from 1998, and the clinical evidence described was preliminary. Cerebrolysin's exact mechanism of action and which specific peptides are responsible for its effects remain unclear."},{"rthcId":"RPEP-00506","title":"Human urotensin-II is a potent vasoconstrictor and agonist for the orphan receptor GPR14.","authors":"Ames, R S; Sarau, H M; Chambers, J K; Willette, R N; Aiyar, N V; Romanic, A M; Louden, C S; Foley, J J; Sauermelch, C F; Coatney, R W; Ao, Z; Disa, J; Holmes, S D; Stadel, J M; Martin, J D; Liu, W S; Glover, G I; Wilson, S; McNulty, D E; Ellis, C E; Elshourbagy, N A; Shabon, U; Trill, J J; Hay, D W; Ohlstein, E H; Bergsma, D J; Douglas, S A","year":1999,"journal":"Nature, 401(6750), 282-6","doi":null,"pmid":"10499587","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00507","title":"Chronic central infusion of growth hormone secretagogues: effects on fos expression and peptide gene expression in the rat arcuate nucleus.","authors":"Bailey, A R; Giles, M; Brown, C H; Bull, P M; Macdonald, L P; Smith, L C; Smith, R G; Leng, G; Dickson, S L","year":1999,"journal":"Neuroendocrinology, 70(2), 83-92","doi":null,"pmid":"10461022","tags":["ghrp","neuropeptides","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Chronic central GH secretagogue infusion upregulated NPY and GHRH gene expression in the arcuate nucleus while altering Fos expression patterns, demonstrating neuroplastic adaptations to sustained receptor stimulation.","whyItMatters":"Chronic peptide use causes the brain to adapt. Understanding these adaptations helps predict long-term effects of GH secretagogue therapy, including changes in appetite (via NPY) and hormone regulation.","specificNumbers":"","methodology":"Animal study using continuous intracerebroventricular infusion of GH secretagogues in rats. Fos expression and neuropeptide mRNA levels (NPY, GHRH, somatostatin, POMC) were measured in the arcuate nucleus by in situ hybridization.","limitations":"Central infusion bypasses normal pharmacokinetics. Rat brain adaptations may differ from human responses. The functional consequences of gene expression changes were not measured."},{"rthcId":"RPEP-00508","title":"Growth hormone-releasing hormone and morphine attenuate growth hormone secretagogue-induced activation of the arcuate nucleus in the male rat.","authors":"Bailey, A R; Honda, K; Smith, R G; Leng, G","year":1999,"journal":"Neuroendocrinology, 70(2), 101-6","doi":null,"pmid":"10461024","tags":["ghrp","opioid-peptides","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"GHRH pretreatment and morphine both attenuated GH secretagogue-induced Fos expression in the arcuate nucleus, demonstrating negative feedback and opioid-GH system crosstalk in GH secretagogue signaling.","whyItMatters":"Understanding the feedback mechanisms that limit GH secretagogue effects helps explain why these peptides can lose efficacy over time and informs dosing strategies to maintain their effectiveness.","specificNumbers":"","methodology":"Animal study in male rats. Systemic GH secretagogue administration was combined with GHRH or morphine pretreatment. Fos protein expression in the arcuate nucleus was quantified as a marker of neuronal activation.","limitations":"Rat study using Fos expression as a proxy for neuronal activation. The functional consequences for GH release were not directly measured. Morphine doses used may not reflect physiological opioid signaling."},{"rthcId":"RPEP-00509","title":"Expression of functional growth hormone secretagogue receptors in human pituitary adenomas: polymerase chain reaction, triple in-situ hybridization and cell culture studies.","authors":"Barlier, A; Zamora, A J; Grino, M; Gunz, G; Pellegrini-Bouiller, I; Morange-Ramos, I; Figarella-Branger, D; Dufour, H; Jaquet, P; Enjalbert, A","year":1999,"journal":"Journal of neuroendocrinology, 11(7), 491-502","doi":null,"pmid":"10444306","tags":["ghrp","cancer","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"GHS-R was expressed in 28 of 30 pituitary adenomas across all subtypes, not just GH-secreting tumors. Functional studies showed GH secretagogues stimulated hormone release from multiple tumor types in culture.","whyItMatters":"If GH secretagogues can stimulate hormone release from pituitary tumors, this has safety implications for patients using these peptides who may have undiagnosed pituitary adenomas (which are surprisingly common).","specificNumbers":"","methodology":"In-vitro study of 30 surgically removed human pituitary adenomas (6 GH, 3 GH-PRL, 6 PRL, 5 ACTH, 1 TSH, 4 gonadotroph, 5 non-secreting). RT-PCR for GHS-R mRNA, triple in-situ hybridization for cellular localization, and cell culture for functional hormone release studies.","limitations":"In-vitro study on surgically removed tumors, which may not represent the full range of pituitary adenomas. Cell culture responses may differ from in-vivo tumor behavior. Clinical significance of receptor expression was not determined."},{"rthcId":"RPEP-00510","title":"The structure, dynamics and orientation of antimicrobial peptides in membranes by multidimensional solid-state NMR spectroscopy.","authors":"Bechinger, B","year":1999,"journal":"Biochimica et biophysica acta, 1462(1-2), 157-83","doi":null,"pmid":"10590307","tags":["antimicrobial-peptides","peptide-design"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Solid-state NMR studies showed antimicrobial peptides adopt amphipathic helical structures oriented parallel to bacterial membrane surfaces, providing a structural basis for their selective membrane disruption mechanism.","whyItMatters":"Knowing exactly how antimicrobial peptides interact with membranes at the atomic level is essential for designing more potent and selective peptide antibiotics to combat antibiotic resistance.","specificNumbers":"","methodology":"Review of solid-state NMR spectroscopy studies using isotopically labeled antimicrobial peptides (cecropins, magainins) in membrane environments. Multiple NMR techniques were used to determine structure, dynamics, and orientation.","limitations":"Model membrane systems may not perfectly replicate bacterial or human cell membranes. NMR provides averaged structural information that may miss dynamic intermediate states. Review focused on a limited number of peptide families."},{"rthcId":"RPEP-00511","title":"Dynorphin A processing enzyme: tissue distribution, isolation, and characterization.","authors":"Berman, Y; Ageyeva, L; Veksler, B; Wood, D; Devi, L A","year":1999,"journal":"Journal of biochemistry, 125(3), 641-7","doi":null,"pmid":"10050055","tags":["opioid-peptides","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"A prodynorphin processing enzyme was isolated and characterized, revealing tissue-specific processing that generates different bioactive dynorphin peptides in brain versus peripheral tissues like adrenal gland and gut.","whyItMatters":"Understanding why different tissues produce different opioid peptides from the same precursor helps explain why opioid signaling varies across body systems and could inform targeted opioid therapies.","specificNumbers":"","methodology":"In-vitro biochemistry study. The processing enzyme was isolated from various rat tissues using chromatography. Tissue distribution was mapped, and cleavage products were identified to characterize tissue-specific processing patterns.","limitations":"In-vitro enzyme characterization in rat tissues. Processing patterns may differ in humans. The functional consequences of tissue-specific processing were not tested."},{"rthcId":"RPEP-00512","title":"The role of oxytocin in relation to female sexual arousal.","authors":"Blaicher, W; Gruber, D; Bieglmayer, C; Blaicher, A M; Knogler, W; Huber, J C","year":1999,"journal":"Gynecologic and obstetric investigation, 47(2), 125-6","doi":null,"pmid":"9949283","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00513","title":"Identification and characterization of a new growth hormone-releasing peptide receptor in the heart.","authors":"Bodart, V; Bouchard, J F; McNicoll, N; Escher, E; Carrière, P; Ghigo, E; Sejlitz, T; Sirois, M G; Lamontagne, D; Ong, H","year":1999,"journal":"Circulation research, 85(9), 796-802","doi":null,"pmid":"10532947","tags":["ghrp","cardiovascular","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"A novel cardiac-specific GHRP receptor distinct from the pituitary GHS-R was identified in rat heart tissue, binding hexarelin with high affinity and mediating cardioprotective effects independently of GH release.","whyItMatters":"The discovery that the heart has its own GHRP receptor means GH secretagogues could be developed specifically for cardiac protection, separate from their GH-releasing effects. This opens a new therapeutic avenue for heart disease.","specificNumbers":"","methodology":"Animal study using radioligand binding on cardiac membranes from normal, GH-deficient, and senescent rats. Receptor specificity was determined by competition binding with various ligands. Functional cardioprotection was confirmed in isolated heart models.","limitations":"Receptor identified in rat hearts; human cardiac receptor confirmation needed. The downstream signaling pathway was not fully characterized. In-vivo cardioprotective dose-response not established."},{"rthcId":"RPEP-00514","title":"Cardiac peptide stability, aprotinin and room temperature: importance for assessing cardiac function in clinical practice.","authors":"Buckley, M G; Marcus, N J; Yacoub, M H","year":1999,"journal":"Clinical science (London, England : 1979), 97(6), 689-95","doi":null,"pmid":"10585896","tags":["natriuretic-peptides","cardiovascular"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"BNP remained stable at room temperature for up to 72 hours without aprotinin, while ANP degraded significantly within hours. This stability makes BNP the most practical natriuretic peptide for routine clinical testing.","whyItMatters":"A blood test is only useful if samples don't degrade during routine handling. BNP's exceptional stability at room temperature is a key reason it became the standard clinical heart failure biomarker over ANP.","specificNumbers":"","methodology":"In-vitro stability study comparing BNP, ANP, and NT-ANP degradation rates in blood samples at room temperature over 72 hours, with and without the protease inhibitor aprotinin.","limitations":"In-vitro stability study. Actual clinical sample handling conditions may vary. Results specific to the assay methods used."},{"rthcId":"RPEP-00515","title":"Vasopeptidase inhibition: a new concept in blood pressure management.","authors":"Burnett, J C","year":1999,"journal":"Journal of hypertension. Supplement : official journal of the International Society of Hypertension, 17(1), S37-43","doi":null,"pmid":"10340842","tags":["natriuretic-peptides","cardiovascular"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Vasopeptidase inhibitors simultaneously increase natriuretic peptide levels (by blocking NEP) and decrease angiotensin II (by blocking ACE), producing superior blood pressure reduction compared to ACE inhibition alone.","whyItMatters":"Combining two mechanisms of blood pressure control in one molecule is more effective and simpler than taking two separate drugs. This concept influenced the development of sacubitril/valsartan (Entresto), now a standard heart failure treatment.","specificNumbers":"","methodology":"Review article covering the pharmacological rationale, preclinical data, and early clinical trial results of vasopeptidase inhibitors (dual ACE/NEP inhibitors) for cardiovascular therapy.","limitations":"Review of early-stage clinical data. First-generation vasopeptidase inhibitors (omapatrilat) were later limited by angioedema risk. The concept was eventually refined in a different drug class."},{"rthcId":"RPEP-00516","title":"The natriuretic peptides in heart failure: diagnostic and therapeutic potentials.","authors":"Chen, H H; Burnett, J C","year":1999,"journal":"Proceedings of the Association of American Physicians, 111(5), 406-16","doi":null,"pmid":"10519161","tags":["natriuretic-peptides","cardiovascular"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Natriuretic peptides have dual clinical potential: as diagnostic/prognostic biomarkers for heart failure and as direct therapeutic agents through vasodilation, diuresis, and suppression of the renin-angiotensin and sympathetic nervous systems.","whyItMatters":"This review captured the moment when natriuretic peptides were transitioning from research curiosities to clinical tools — both as blood tests and potential treatments. Both applications have since become clinical reality.","specificNumbers":"","methodology":"Comprehensive review of natriuretic peptide biology, diagnostic applications, and therapeutic potential in heart failure, covering ANP, BNP, and CNP.","limitations":"Review from 1999; some therapeutic applications described were still in early development. Long-term outcomes of natriuretic peptide therapy were not yet established."},{"rthcId":"RPEP-00517","title":"Role of opioid ligands in the irritable bowel syndrome.","authors":"Corazziari, E","year":1999,"journal":"Canadian journal of gastroenterology = Journal canadien de gastroenterologie, 13 Suppl A, 71A-75A","doi":null,"pmid":"10202212","tags":["opioid-peptides","gut-healing","pain"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Endogenous opioid peptides regulate visceral pain sensitivity, gastrointestinal motility, and secretion through mu, delta, and kappa receptors in the brain, spinal cord, and enteric nervous system, with dysfunction potentially underlying IBS symptoms.","whyItMatters":"IBS affects up to 15% of the population with limited treatment options. Understanding the opioid peptide system in the gut could lead to targeted therapies that address specific symptoms — pain, diarrhea, or constipation — through different opioid receptor subtypes.","specificNumbers":"","methodology":"Review article synthesizing data on endogenous opioid peptide distribution, receptor pharmacology, and functional effects on gut sensory and motor function, with application to IBS pathophysiology and treatment.","limitations":"Review based on knowledge through 1999. Some proposed mechanisms were still hypothetical. The complexity of IBS pathophysiology means opioid dysfunction is only part of the picture."},{"rthcId":"RPEP-00518","title":"Plant cyclotides: A unique family of cyclic and knotted proteins that defines the cyclic cystine knot structural motif.","authors":"Craik, D J; Daly, N L; Bond, T; Waine, C","year":1999,"journal":"Journal of molecular biology, 294(5), 1327-36","doi":null,"pmid":"10600388","tags":["cyclic-peptides","antimicrobial-peptides","peptide-design"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Sixteen novel cyclotides were identified from three plant species, all sharing the cyclic cystine knot motif that confers exceptional thermal, chemical, and enzymatic stability, with diverse bioactivities including antimicrobial and anti-HIV effects.","whyItMatters":"Cyclotides' extraordinary stability solves one of the biggest problems in peptide drug development — most peptides are quickly destroyed in the body. Their circular, knotted structure could serve as a template for designing stable oral peptide drugs.","specificNumbers":"","methodology":"In-vitro study using extraction, HPLC purification, mass spectrometry, and NMR structural characterization to identify and characterize cyclotides from Viola hederaceae, Viola odorata, and Oldenlandia affinis plant extracts.","limitations":"Discovery and structural characterization study. Bioactivities described are primarily from initial screening. Detailed mechanism of action and therapeutic potential require further study."},{"rthcId":"RPEP-00519","title":"Solution structure by NMR of circulin A: a macrocyclic knotted peptide having anti-HIV activity.","authors":"Daly, N L; Koltay, A; Gustafson, K R; Boyd, M R; Casas-Finet, J R; Craik, D J","year":1999,"journal":"Journal of molecular biology, 285(1), 333-45","doi":null,"pmid":"9878410","tags":["cyclic-peptides","infection","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Circulin A's 3D structure reveals a cyclic cystine knot fold with exposed hydrophobic and positively charged surface patches, providing a structural basis for its membrane-disrupting anti-HIV activity.","whyItMatters":"Knowing the 3D structure of an anti-HIV peptide enables rational drug design — researchers can identify which structural features are essential for activity and engineer improved analogs.","specificNumbers":"","methodology":"Structural biology study using 2D proton NMR spectroscopy with distance geometry and simulated annealing to determine circulin A's solution structure in water.","limitations":"Structure determined in water, which may differ from conformation at viral membranes. The exact mechanism of anti-HIV activity (membrane disruption vs. specific receptor binding) was not definitively established."},{"rthcId":"RPEP-00520","title":"Structural features of helical antimicrobial peptides: their potential to modulate activity on model membranes and biological cells.","authors":"Dathe, M; Wieprecht, T","year":1999,"journal":"Biochimica et biophysica acta, 1462(1-2), 71-87","doi":null,"pmid":"10590303","tags":["antimicrobial-peptides","peptide-design","infection"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Antimicrobial peptide selectivity follows a balance: moderate hydrophobicity and amphipathicity maximize bacterial killing with minimal human cell toxicity, while excessive hydrophobicity increases toxicity without improving antibacterial activity.","whyItMatters":"These structural rules provide a practical guide for designing antimicrobial peptides that are effective antibiotics without the toxicity that has limited previous peptide drug candidates.","specificNumbers":"","methodology":"Review article synthesizing structure-activity relationship studies of helical antimicrobial peptides, covering hydrophobicity, charge, helical propensity, and amphipathicity effects on model membranes and biological cells.","limitations":"Structure-activity rules derived largely from model membrane studies and simplified peptide analogs. In-vivo complexity (serum binding, protease degradation, tissue distribution) adds additional challenges."},{"rthcId":"RPEP-00521","title":"Modulation of antibacterial peptide activity by products of Porphyromonas gingivalis and Prevotella spp.","authors":"Devine, D A; Marsh, P D; Percival, R S; Rangarajan, M; Curtis, M A","year":1999,"journal":"Microbiology (Reading, England), 145 ( Pt 4), 965-971","doi":"10.1099/13500872-145-4-965","pmid":"10220176","tags":["antimicrobial-peptides","infection"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Periodontal pathogens P. gingivalis and Prevotella spp. produce extracellular proteases that degrade and inactivate antimicrobial peptides, representing a bacterial evasion mechanism against innate immune defenses in the oral cavity.","whyItMatters":"If oral bacteria can destroy the mouth's antimicrobial peptide defenses, this provides a mechanism for chronic gum disease and suggests that protease-resistant peptide antibiotics might be needed to treat periodontal infections.","specificNumbers":"","methodology":"In-vitro study using double-layer agarose diffusion assays and broth microdilution assays to test antimicrobial peptide activity against periodontal bacteria, with culture supernatant experiments to assess protease-mediated inactivation.","limitations":"In-vitro study; protease activity in the complex oral environment may differ. Not all periodontal bacteria were tested. The relative importance of this evasion mechanism versus other virulence factors is unclear."},{"rthcId":"RPEP-00522","title":"Endocrine and non-endocrine activities of growth hormone secretagogues in humans.","authors":"Ghigo, E; Arvat, E; Broglio, F; Giordano, R; Gianotti, L; Muccioli, G; Papotti, M; Graziani, A; Bisi, G; Deghenghi, R; Camanni, F","year":1999,"journal":"Hormone research, 51 Suppl 3, 9-15","doi":null,"pmid":"10592438","tags":["ghrp","hormone-optimization","receptor-signaling"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"GH secretagogues have clinically significant non-endocrine effects including cardiovascular protection, orexigenic (appetite-stimulating) activity, sleep architecture improvement, and potential anti-aging properties mediated by widespread GHS receptor distribution.","whyItMatters":"Understanding the full spectrum of GH secretagogue effects is essential for their therapeutic development. The non-endocrine effects may be as clinically important as GH release, expanding potential applications to cardiovascular disease, eating disorders, and age-related decline.","specificNumbers":"","methodology":"Comprehensive review of human clinical and preclinical data on the endocrine (GH, PRL, ACTH release) and non-endocrine (cardiovascular, appetite, sleep, aging) effects of GH secretagogues.","limitations":"Review based on a mix of clinical and preclinical data. Some non-endocrine effects were preliminary. Long-term consequences of multi-system activation not fully understood."},{"rthcId":"RPEP-00523","title":"Pharmacokinetic-pharmacodynamic modeling of ipamorelin, a growth hormone releasing peptide, in human volunteers.","authors":"Gobburu, J V; Agersø, H; Jusko, W J; Ynddal, L","year":1999,"journal":"Pharmaceutical research, 16(9), 1412-6","doi":null,"pmid":"10496658","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00524","title":"Homeostasis, thymic hormones and aging.","authors":"Goya, R G; Bolognani, F","year":1999,"journal":"Gerontology, 45(3), 174-8","doi":null,"pmid":"10202264","tags":["thymosin-alpha-1","immune-function","anti-aging"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"The thymic-pituitary axis forms a bidirectional neuroendocrine circuit that deteriorates with age, contributing to immunosenescence. Thymic peptide supplementation may restore immune-endocrine homeostasis in aging.","whyItMatters":"Age-related immune decline is a major driver of susceptibility to infections, cancer, and chronic disease in the elderly. Understanding the thymic-hormonal connection could lead to interventions that restore immune function during aging.","specificNumbers":"","methodology":"Review article covering the immune-neuroendocrine homeostatic network, the role of thymic epithelial factors, and age-related disruption of thymic-pituitary communication.","limitations":"Review based largely on animal data. The degree to which thymic peptide supplementation can reverse age-related immune decline in humans was not established."},{"rthcId":"RPEP-00525","title":"The thymus-pituitary axis and its changes during aging.","authors":"Goya, R G; Brown, O A; Bolognani, F","year":1999,"journal":"Neuroimmunomodulation, 6(1-2), 137-42","doi":null,"pmid":"9876244","tags":["thymosin-alpha-1","immune-function","anti-aging"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Aging causes progressive disruption of the pituitary-thymic bidirectional circuit: reduced thymic peptide production, altered pituitary hormone output, and impaired integration between immune and endocrine systems, creating a self-reinforcing decline.","whyItMatters":"Understanding the specific mechanisms of thymic-pituitary deterioration in aging identifies intervention points where peptide therapy could break the vicious cycle of immune-endocrine decline.","specificNumbers":"","methodology":"Review of experimental and clinical evidence documenting age-related changes in thymic-pituitary communication, including thymic hormone levels, pituitary hormone changes, and immune function correlates.","limitations":"Review synthesizing data from multiple model systems. The relative contribution of thymic versus pituitary changes to overall immune aging is debated. Therapeutic implications were largely theoretical at time of publication."},{"rthcId":"RPEP-00526","title":"Oral administration of peptidergic growth hormone (GH) secretagogue KP102 stimulates GH release in goats.","authors":"Hashizume, T; Kawai, M; Ohtsuki, K; Ishii, A; Numata, M","year":1999,"journal":"Domestic animal endocrinology, 16(1), 31-9","doi":null,"pmid":"10081661","tags":["ghrp","oral-peptides","hormone-optimization"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Oral GHRP-2 (5-10 mg/kg) stimulated significant GH release in 1-month-old goats (peak at 15 min) but not in 3-month-old goats, demonstrating age-dependent oral peptide bioavailability in ruminants.","whyItMatters":"Demonstrating oral peptide activity in large animals is important for both agricultural applications (promoting growth) and for understanding oral peptide delivery across species. The age-dependent absorption highlights gut maturation as a factor.","specificNumbers":"","methodology":"Animal study in goats. GHRP-2 dissolved in saline was administered orally twice at 2-hour intervals to 1-month and 3-month-old goats (n=5-6 per group). Plasma GH levels were measured over time.","limitations":"Ruminant digestive system differs significantly from human. Age-dependent response may reflect gut development specific to goats. Relatively high doses required (5-10 mg/kg). Not directly translatable to human oral delivery."},{"rthcId":"RPEP-00527","title":"GHRP-6-induced changes in electrical activity of single cells in the arcuate, ventromedial and periventricular nucleus neurones [correction of nuclei] of a hypothalamic slice preparation in vitro.","authors":"Hewson, A K; Viltart, O; McKenzie, D N; Dyball, R E; Dickson, S L","year":1999,"journal":"Journal of neuroendocrinology, 11(12), 919-23","doi":null,"pmid":"10583726","tags":["ghrp","neuropeptides","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"GHRP-6 excited most arcuate nucleus neurons but had mixed excitatory/inhibitory effects in ventromedial and periventricular hypothalamic nuclei, revealing multi-circuit brain modulation by GH secretagogues.","whyItMatters":"Understanding which brain regions and circuits are affected by GH secretagogues helps predict their effects on appetite, metabolism, stress, and other functions controlled by the hypothalamus.","specificNumbers":"","methodology":"In-vitro brain slice electrophysiology study. Extracellular recordings measured GHRP-6 effects on individual neurons in the arcuate, ventromedial, and periventricular nuclei of rat hypothalamic slices.","limitations":"In-vitro brain slice preparation lacks normal neural connections and blood-brain barrier. Individual neuron recordings may not reflect integrated circuit behavior in vivo."},{"rthcId":"RPEP-00528","title":"Pentadecapeptide BPC 157 attenuates disturbances induced by neuroleptics: the effect on catalepsy and gastric ulcers in mice and rats.","authors":"Jelovac, N; Sikiric, P; Rucman, R; Petek, M; Marovic, A; Perovic, D; Seiwerth, S; Mise, S; Turkovic, B; Dodig, G; Miklic, P; Buljat, G; Prkacin, I","year":1999,"journal":"European journal of pharmacology, 379(1), 19-31","doi":null,"pmid":"10499368","tags":["bpc-157","neuroprotection","gut-healing"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"BPC-157 attenuated catalepsy and gastric ulcers induced by haloperidol, fluphenazine, and reserpine at both 10 μg/kg and 10 ng/kg doses, demonstrating broad protective effects against neuroleptic side effects.","whyItMatters":"Antipsychotic side effects are a major reason patients stop taking their medication. A co-treatment that reduces muscle stiffness and stomach damage without interfering with antipsychotic efficacy could dramatically improve treatment adherence.","specificNumbers":"","methodology":"Animal studies in mice and rats. BPC-157 was administered IP at two doses alongside haloperidol, fluphenazine, or reserpine. Catalepsy was measured by bar test, and gastric lesions were scored macroscopically.","limitations":"Animal study. Whether BPC-157 would interfere with the antipsychotic therapeutic effect was not conclusively assessed. Translation to human psychiatric care is speculative."},{"rthcId":"RPEP-00529","title":"The effect of a novel pentadecapeptide BPC 157 on development of tolerance and physical dependence following repeated administration of diazepam.","authors":"Jelovac, N; Sikiric, P; Rucman, R; Petek, M; Perovic, D; Marovic, A; Anic, T; Seiwerth, S; Mise, S; Pigac, B; Duplancie, B; Turkovic, B; Dodig, G; Prkacin, I; Stancic-Rokotov, D; Zoricic, I; Aralica, G; Sebecic, B; Ziger, T; Slobodnjak, Z","year":1999,"journal":"The Chinese journal of physiology, 42(3), 171-9","doi":null,"pmid":"10707891","tags":["bpc-157","anxiety-mood","peptide-safety"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"BPC-157 co-administration with chronic diazepam (10 days) prevented tolerance development, maintained anticonvulsant efficacy, and reduced withdrawal seizure severity at both 10 μg/kg and 10 ng/kg doses in rats.","whyItMatters":"Benzodiazepine dependence is a major clinical problem. A co-treatment that prevents tolerance and dependence without interfering with the therapeutic effect would transform how these medications are used.","specificNumbers":"","methodology":"Animal study in rats. BPC-157 (10 μg/kg or 10 ng/kg IP) was co-administered with diazepam (5 mg/kg IP) twice daily for 10 days. Anticonvulsant efficacy, tolerance, and pentylenetetrazol-induced withdrawal seizures were assessed.","limitations":"Rat study only. The GABAergic interaction mechanism was not fully elucidated. Translation to human benzodiazepine use is unknown. 10-day timeframe may not reflect longer-term dependence patterns."},{"rthcId":"RPEP-00530","title":"Ipamorelin, a new growth-hormone-releasing peptide, induces longitudinal bone growth in rats.","authors":"Johansen, P B; Nowak, J; Skjaerbaek, C; Flyvbjerg, A; Andreassen, T T; Wilken, M; Orskov, H","year":1999,"journal":"Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society, 9(2), 106-13","doi":null,"pmid":"10373343","tags":["ipamorelin","bone-joint","hormone-optimization"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Ipamorelin (18-450 μg/day SC, three daily injections for 15 days) increased longitudinal bone growth rate and body weight dose-dependently in rats, with sustained GH release throughout the treatment period.","whyItMatters":"This is the first demonstration that ipamorelin can translate its selective GH-releasing activity into actual bone growth. The sustained response without desensitization is particularly important for potential therapeutic applications.","specificNumbers":"","methodology":"Animal study in rats. Ipamorelin at 0, 18, 90, and 450 μg/day was injected subcutaneously three times daily for 15 days. Longitudinal bone growth rate (proximal tibial epiphysis), body weight, and plasma GH were measured.","limitations":"Rat study with relatively short duration. Bone growth rate in young growing rats may not predict effects in adult bone metabolism. No comparison to direct GH injection."},{"rthcId":"RPEP-00531","title":"STZ-induced diabetes decreases and insulin normalizes POMC mRNA in arcuate nucleus and pituitary in rats.","authors":"Kim, E M; Grace, M K; Welch, C C; Billington, C J; Levine, A S","year":1999,"journal":"The American journal of physiology, 276(5), R1320-6","doi":"10.1152/ajpregu.1999.276.5.R1320","pmid":"10233022","tags":["opioid-peptides","diabetes","neuropeptides"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"STZ-induced diabetes decreased POMC mRNA by significant amounts in the hypothalamic arcuate nucleus and anterior pituitary by 2-4 weeks, with insulin treatment (3 weeks) normalizing expression levels.","whyItMatters":"Diabetic neuropathy causes significant pain and suffering. If diabetes suppresses the brain's natural opioid production, this provides a mechanism for diabetic pain syndromes and suggests opioid peptide supplementation could help.","specificNumbers":"","methodology":"Animal study in rats with STZ-induced diabetes. Three groups: 2-week diabetic, 4-week diabetic, and 4-week diabetic with 3 weeks insulin treatment. POMC mRNA measured by in situ hybridization in arcuate nucleus and anterior pituitary.","limitations":"Rat diabetes model (STZ) may not perfectly replicate human type 1 or type 2 diabetes. POMC mRNA changes don't necessarily equate to proportional changes in active peptide levels. The functional pain consequences were not directly measured."},{"rthcId":"RPEP-00532","title":"Ghrelin is a growth-hormone-releasing acylated peptide from stomach.","authors":"Kojima, M; Hosoda, H; Date, Y; Nakazato, M; Matsuo, H; Kangawa, K","year":1999,"journal":"Nature, 402(6762), 656-60","doi":null,"pmid":"10604470","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00533","title":"Clinical implications of amylin and amylin deficiency.","authors":"Kruger, D F; Gatcomb, P M; Owen, S K","year":1999,"journal":"The Diabetes educator, 25(3), 389-97; quiz 398","doi":null,"pmid":"10531859","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00534","title":"Identification of urotensin II as the endogenous ligand for the orphan G-protein-coupled receptor GPR14.","authors":"Liu, Q; Pong, S S; Zeng, Z; Zhang, Q; Howard, A D; Williams, D L; Davidoff, M; Wang, R; Austin, C P; McDonald, T P; Bai, C; George, S R; Evans, J F; Caskey, C T","year":1999,"journal":"Biochemical and biophysical research communications, 266(1), 174-8","doi":null,"pmid":"10581185","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00535","title":"Activation of arcuate nucleus neurons by systemic administration of leptin and growth hormone-releasing peptide-6 in normal and fasted rats.","authors":"Luckman, S M; Rosenzweig, I; Dickson, S L","year":1999,"journal":"Neuroendocrinology, 70(2), 93-100","doi":null,"pmid":"10461023","tags":["ghrp","neuropeptides","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Leptin and GHRP-6 activate different populations of arcuate nucleus neurons, with limited overlap, indicating independent pathways for fat-derived and peptide-stimulated growth hormone regulation.","whyItMatters":"Understanding that leptin (fat signal) and GHRP-6 (peptide signal) reach the GH system through independent brain pathways explains why GH secretagogues can work even when leptin signaling is disrupted by obesity.","specificNumbers":"","methodology":"Animal study using Fos immunohistochemistry in normal and fasted male rats after systemic leptin, GHRP-6, or combined administration. Double-labeling identified overlap between activated neuron populations.","limitations":"Fos expression is an indirect marker of neural activation. The specific neuron subtypes in each population were not fully characterized. Acute dosing may not reflect chronic signaling patterns."},{"rthcId":"RPEP-00536","title":"Natriuretic peptides in assessment of left-ventricular dysfunction.","authors":"Mair, J; Friedl, W; Thomas, S; Puschendorf, B","year":1999,"journal":"Scandinavian journal of clinical and laboratory investigation. Supplementum, 230, 132-42","doi":null,"pmid":"10389212","tags":["natriuretic-peptides","cardiovascular"],"studyType":"review","evidenceStrength":"strong","keyFinding":"BNP demonstrates superior sensitivity over ANP for detecting subclinical left ventricular dysfunction, supporting its use as a screening tool for early identification of heart failure risk.","whyItMatters":"Many people have weakened hearts without knowing it. A simple blood test that catches this early allows treatment before irreversible damage occurs, potentially preventing heart failure.","specificNumbers":"","methodology":"Review of clinical studies evaluating ANP and BNP as biomarkers for left ventricular dysfunction screening, diagnosis, and prognosis assessment.","limitations":"Review based on available studies through 1999. Optimal cutoff values and screening protocols were still being refined. Cost-effectiveness of population screening not established."},{"rthcId":"RPEP-00537","title":"Thymosin beta4 accelerates wound healing.","authors":"Malinda, K M; Sidhu, G S; Mani, H; Banaudha, K; Maheshwari, R K; Goldstein, A L; Kleinman, H K","year":1999,"journal":"The Journal of investigative dermatology, 113(3), 364-8","doi":null,"pmid":"10469335","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Thymosin beta-4 (Tβ4) applied topically or intraperitoneally to full-thickness wounds in rats accelerated skin regrowth by 42% at day 4 and up to 61% at day 7 compared to saline controls. Treated wounds also contracted at least 11% more than controls by day 7. The peptide increased collagen deposition and new blood vessel formation in the wound. In lab assays, thymosin beta-4 stimulated keratinocyte (skin cell) migration 2–3-fold at doses as low as 10 picograms — an extraordinarily small amount.","whyItMatters":"This 1999 study was one of the first to demonstrate thymosin beta-4's wound healing potential with specific numbers. The fact that such tiny amounts of the peptide could dramatically accelerate skin regrowth, increase collagen production, and promote new blood vessel formation made it a landmark finding. It helped establish thymosin beta-4 as one of the most promising wound-healing peptides and spurred decades of subsequent research into its clinical applications.","specificNumbers":"","methodology":"Researchers used a rat full-thickness wound model, applying thymosin beta-4 either topically to the wound or via intraperitoneal injection, with saline as a control. They measured wound reepithelialization (skin regrowth) and contraction at days 4 and 7. Collagen deposition and angiogenesis were assessed histologically. In parallel, keratinocyte migration was measured using a Boyden chamber assay with varying concentrations of thymosin beta-4.","limitations":"This is an animal study in rats — wound healing in rodents differs from humans in important ways (rats heal partly by contraction, humans primarily by reepithelialization). The study used a relatively short observation period (7 days). No toxicity or long-term safety data were reported. The specific mechanisms by which thymosin beta-4 produces these effects were not fully elucidated in this study."},{"rthcId":"RPEP-00538","title":"Methylprednisolone does not inhibit the release of growth hormone after intravenous injection of a novel growth hormone secretagogue in rats.","authors":"Malmlöf, K; Johansen, P B; Haahr, P M; Wilken, M; Oxlund, H","year":1999,"journal":"Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society, 9(6), 445-50","doi":null,"pmid":"10629165","tags":["ipamorelin","hormone-optimization","bone-joint"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Ipamorelin maintained GH-releasing activity during 8 days of methylprednisolone treatment in rats and partially preserved longitudinal bone growth over 15 days despite glucocorticoid-induced growth suppression.","whyItMatters":"Children on chronic steroids (for asthma, autoimmune diseases, transplants) often fail to grow properly. A GH secretagogue that works despite steroids could preserve their growth and development.","specificNumbers":"","methodology":"Two animal experiments in rats: (1) GH release after ipamorelin with/without 8-day MP treatment, (2) 15-day bone growth study with ipamorelin during MP administration. Plasma GH and tibial bone growth measured.","limitations":"Rat study. Bone growth was only partially preserved, not fully restored. The mechanism by which ipamorelin bypasses glucocorticoid suppression was not determined. Human pediatric data needed."},{"rthcId":"RPEP-00539","title":"Molecular recognition of macrocyclic peptidomimetic inhibitors by HIV-1 protease.","authors":"Martin, J L; Begun, J; Schindeler, A; Wickramasinghe, W A; Alewood, D; Alewood, P F; Bergman, D A; Brinkworth, R I; Abbenante, G; March, D R; Reid, R C; Fairlie, D P","year":1999,"journal":"Biochemistry, 38(25), 7978-88","doi":null,"pmid":"10387041","tags":["cyclic-peptides","infection","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"High-resolution crystal structures of seven macrocyclic HIV protease inhibitors revealed specific binding interactions, demonstrating how cyclic peptide scaffolds can achieve potent enzyme inhibition with improved drug properties.","whyItMatters":"HIV protease inhibitors are a cornerstone of AIDS treatment. Designing cyclic versions with better stability and bioavailability could improve existing drugs and inspire peptidomimetic approaches for other diseases.","specificNumbers":"","methodology":"X-ray crystallography study determining high-resolution structures of seven macrocyclic peptidomimetics complexed with HIV-1 protease. Structure-activity analysis correlated binding features with inhibitory potency.","limitations":"Structural study focused on binding interactions, not clinical pharmacology. In-vitro potency may not predict in-vivo drug performance. Synthesis of macrocyclic compounds can be challenging at scale."},{"rthcId":"RPEP-00540","title":"Recent advances with the CRF1 receptor: design of small molecule inhibitors, receptor subtypes and clinical indications.","authors":"McCarthy, J R; Heinrichs, S C; Grigoriadis, D E","year":1999,"journal":"Current pharmaceutical design, 5(5), 289-315","doi":null,"pmid":"10213797","tags":["neuropeptides","anxiety-mood","receptor-signaling"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Non-peptide CRF1 receptor antagonists selectively block stress signaling and show anxiolytic and antidepressant effects in animal models, with potential clinical applications spanning anxiety, depression, addiction, and inflammation.","whyItMatters":"Stress-related disorders (anxiety, depression, PTSD) affect hundreds of millions globally. Targeting the CRF system — the body's core stress pathway — represents a fundamentally different approach from existing medications.","specificNumbers":"","methodology":"Comprehensive review covering CRF receptor cloning, subtype characterization, non-peptide antagonist development, preclinical pharmacology, and proposed clinical applications.","limitations":"Review from 1999; clinical trial results were not yet available. CRF1 antagonists have had mixed clinical trial results since. Animal models of anxiety and depression have limitations in predicting human drug response."},{"rthcId":"RPEP-00541","title":"Preservation of growth hormone secretion in response to growth hormone-releasing peptide-2 during prednisone therapy.","authors":"Meacham, L R; Culler, F L; Abdul-Latif, H; Sullivan, K M; Bowers, C Y","year":1999,"journal":"Metabolism: clinical and experimental, 48(5), 585-9","doi":null,"pmid":"10337858","tags":["ghrp","hormone-optimization","clinical-trials"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"GHRP-2 preserved GH secretory response in 8 children during prednisone therapy, maintaining GH release levels comparable to pre-treatment baseline, suggesting GHRP-2 bypasses glucocorticoid-induced somatostatin excess.","whyItMatters":"Thousands of children need chronic steroids for asthma, arthritis, and other conditions. Preserving their GH function could prevent the growth stunting that currently accompanies steroid treatment.","specificNumbers":"","methodology":"Clinical trial in 8 children requiring prednisone therapy. GH stimulation tests with GHRP-2 were performed before and during prednisone treatment. GH peak levels and secretory patterns were compared.","limitations":"Very small study (8 children). GH stimulation test results don't guarantee actual growth preservation. Long-term growth outcomes not assessed. Open-label design."},{"rthcId":"RPEP-00542","title":"Growth hormone secretagogues: the clinical future.","authors":"Micic, D; Casabiell, X; Gualillo, O; Pombo, M; Dieguez, C; Casanueva, F F","year":1999,"journal":"Hormone research, 51 Suppl 3, 29-33","doi":null,"pmid":"10592441","tags":["ghrp","hormone-optimization","clinical-trials"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"GH secretagogues offer three clinical futures: oral GH deficiency treatment replacing injections, improved GH deficiency diagnostics, and expanded indications for partial GH insufficiency in aging, obesity, and critical illness.","whyItMatters":"GH deficiency affects quality of life in children and adults. Oral GH secretagogues that produce more natural GH release patterns could transform treatment from burdensome daily injections to simple pills.","specificNumbers":"","methodology":"Review of clinical data and future therapeutic directions for GH secretagogues, covering GHRP-6, hexarelin, ipamorelin, MK-677, and other compounds.","limitations":"Review based on clinical data through 1999. Long-term efficacy and safety of chronic GH secretagogue use were not yet established. Regulatory approval pathways were uncertain."},{"rthcId":"RPEP-00543","title":"The cell biology of the prohormone convertases PC1 and PC2.","authors":"Muller, L; Lindberg, I","year":1999,"journal":"Progress in nucleic acid research and molecular biology, 63, 69-108","doi":null,"pmid":"10506829","tags":["peptide-processing","prohormone-convertase"],"studyType":"review","evidenceStrength":"reference","keyFinding":"PC1 and PC2 follow markedly different activation pathways. PC1 undergoes rapid propeptide cleavage in the endoplasmic reticulum and is further activated by a carboxyl-terminal processing event. PC2, by contrast, has much longer folding times, exits the ER without propeptide cleavage, and requires association with the neuroendocrine-specific protein 7B2 to become catalytically active.\n\nThe 7B2 protein is internally cleaved into a 21-kDa fragment and a 31-residue carboxy-terminal peptide once the complex reaches the trans-Golgi network. PC2 propeptide removal occurs later in secretory granules, likely through autocatalysis, but without prior 7B2 encounter, PC2 cannot generate an active enzyme. A 36-residue internal segment of 7B2 appears to mediate the critical conformational changes.","whyItMatters":"PC1 and PC2 are the master switches for peptide hormone activation. They process proinsulin into insulin, POMC into endorphins and ACTH, and hundreds of other prohormones into their active forms. Mutations or dysfunction in these enzymes cause severe hormonal disorders including obesity, diabetes, and adrenal insufficiency. Understanding their biology is essential for both basic peptide science and developing therapies that target the peptide processing machinery.","specificNumbers":"PC1: rapid ER propeptide cleavage + C-terminal activation; PC2: slow folding, requires 7B2, propeptide removal in secretory granules; 7B2 cleaved into 21-kDa + 31-residue fragments","methodology":"Narrative review of published cell biology, biochemistry, and molecular biology research on PC1 and PC2 prohormone convertases in neuroendocrine cells.","limitations":"Review from 1999; some mechanisms described as unknown have since been clarified. Does not cover subsequently identified prohormone convertases or regulatory pathways."},{"rthcId":"RPEP-00544","title":"Oral administration of the growth hormone secretagogue MK-677 increases markers of bone turnover in healthy and functionally impaired elderly adults. The MK-677 Study Group.","authors":"Murphy, M G; Bach, M A; Plotkin, D; Bolognese, J; Ng, J; Krupa, D; Cerchio, K; Gertz, B J","year":1999,"journal":"Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 14(7), 1182-8","doi":null,"pmid":"10404019","tags":["mk-677","bone-joint","clinical-trials"],"studyType":"RCT","evidenceStrength":"strong","keyFinding":"MK-677 increased bone formation markers at 2 and 12 months in healthy elderly and in hip fracture patients, with sustained IGF-1 elevation, demonstrating prolonged bone-building potential in age-related bone loss.","whyItMatters":"Osteoporosis and hip fractures are devastating in the elderly. An oral medication that stimulates bone formation for at least a year could help prevent fractures and improve recovery after hip surgery.","specificNumbers":"","methodology":"Two randomized, double-blind, placebo-controlled studies: (1) healthy elderly subjects treated with MK-677 for up to 12 months, (2) elderly hip fracture patients during recovery. Bone turnover markers and IGF-1 measured.","limitations":"Bone markers are surrogates for bone density. Actual fracture prevention was not assessed. Sample sizes and specific population details limited in abstract. Long-term safety of IGF-1 elevation in elderly needs monitoring."},{"rthcId":"RPEP-00545","title":"Dynorphin A enhances mitogen-induced proliferative response and interleukin-2 production of rat splenocytes.","authors":"Ni, X; Lin, B C; Song, C Y; Wang, C H","year":1999,"journal":"Neuropeptides, 33(2), 137-43","doi":null,"pmid":"10657483","tags":["opioid-peptides","immune-function"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Dynorphin A enhanced mitogen-induced proliferation of rat splenocytes and increased IL-2 production, demonstrating immunostimulatory activity for this previously undercharacterized opioid peptide.","whyItMatters":"This expands understanding of how the opioid system regulates immunity. Dynorphin A's immune-boosting effect suggests all three major opioid peptide families participate in immune regulation, each potentially through different mechanisms.","specificNumbers":"","methodology":"In-vitro study measuring proliferative response and IL-2 production of rat splenocytes treated with dynorphin A in the presence of mitogens (ConA, PHA).","limitations":"In-vitro study using rat splenocytes with mitogen stimulation. Effects in vivo and in human immune cells may differ. The specific opioid receptor subtype mediating the effect was not identified."},{"rthcId":"RPEP-00546","title":"Natriuretic peptides as markers of cardiotoxicity during doxorubicin treatment for non-Hodgkin's lymphoma.","authors":"Nousiainen, T; Jantunen, E; Vanninen, E; Remes, J; Vuolteenaho, O; Hartikainen, J","year":1999,"journal":"European journal of haematology, 62(2), 135-41","doi":null,"pmid":"10052718","tags":["natriuretic-peptides","cancer","cardiovascular"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Serial BNP measurements detected doxorubicin-induced cardiotoxicity before clinical symptoms or echocardiographic changes in 30 lymphoma patients, with BNP rising progressively with cumulative drug exposure.","whyItMatters":"Doxorubicin is one of the most effective cancer drugs but causes irreversible heart damage. A simple blood test that detects early cardiac injury could allow dose adjustments before permanent damage occurs, saving both hearts and lives.","specificNumbers":"","methodology":"Prospective cohort study in 30 non-Hodgkin's lymphoma patients receiving CHOP chemotherapy. Serial ANP, BNP, and echocardiography performed throughout treatment up to cumulative doxorubicin doses of 400-500 mg/m².","limitations":"30 patients — moderate sample. ANP was less useful. Specific BNP cutoff values for clinical decision-making were not established. Not all types of cardiotoxicity may be detected by BNP."},{"rthcId":"RPEP-00547","title":"The amylin analog pramlintide improves glycemic control and reduces postprandial glucagon concentrations in patients with type 1 diabetes mellitus.","authors":"Nyholm, B; Orskov, L; Hove, K Y; Gravholt, C H; Møller, N; Alberti, K G; Moyses, C; Kolterman, O; Schmitz, O","year":1999,"journal":"Metabolism: clinical and experimental, 48(7), 935-41","doi":null,"pmid":"10421239","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00548","title":"NMR structural characterization of cecropin A(1-8) - magainin 2(1-12) and cecropin A (1-8) - melittin (1-12) hybrid peptides.","authors":"Oh, D; Shin, S Y; Kang, J H; Hahm, K S; Kim, K L; Kim, Y","year":1999,"journal":"The journal of peptide research : official journal of the American Peptide Society, 53(5), 578-89","doi":null,"pmid":"10424354","tags":["antimicrobial-peptides","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Structural comparison revealed the cecropin-magainin hybrid has a bent helix with different hydrophobic surface distribution than the cecropin-melittin hybrid, explaining its superior bacterial selectivity and lower human cell toxicity.","whyItMatters":"Understanding why one hybrid peptide is more selective than another at the atomic level provides precise design rules for creating effective antimicrobial peptides that spare human cells.","specificNumbers":"","methodology":"NMR structural study determining 3D solution structures of CA(1-8)-MA(1-12) and CA(1-8)-ME(1-12) hybrid peptides in trifluoroethanol/water, with structural comparison to explain activity differences.","limitations":"Structures determined in organic solvent mixture, not actual membrane environment. Activity differences may involve factors beyond the structural features identified."},{"rthcId":"RPEP-00549","title":"Pulmonary clearance of adrenomedullin is reduced during the late stage of sepsis.","authors":"Ornan, D A; Chaudry, I H; Wang, P","year":1999,"journal":"Biochimica et biophysica acta, 1427(2), 315-21","doi":null,"pmid":"10216248","tags":["neuropeptides","infection","cardiovascular"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Pulmonary clearance of adrenomedullin was significantly reduced during late-stage sepsis in rats, contributing to ADM accumulation and the hemodynamic collapse of septic shock.","whyItMatters":"Septic shock kills millions annually. Understanding that the lungs fail to clear vasodilatory peptides during late sepsis provides a new therapeutic target — restoring ADM clearance or blocking excess ADM could prevent fatal blood pressure collapse.","specificNumbers":"","methodology":"Animal study using a rat polymicrobial sepsis model. Adrenomedullin levels and pulmonary clearance were measured during early (hyperdynamic) and late (hypodynamic) phases of sepsis.","limitations":"Rat sepsis model may not perfectly replicate human sepsis. The exact mechanism of reduced pulmonary clearance was not identified. Single peptide focus may miss interactions with other vasoactive mediators."},{"rthcId":"RPEP-00550","title":"Somatostatin and its receptor family.","authors":"Patel, Y C","year":1999,"journal":"Frontiers in neuroendocrinology, 20(3), 157-98","doi":null,"pmid":"10433861","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00551","title":"Pentadecapeptide BPC 157 attenuates gastric lesions induced by alloxan in rats and mice.","authors":"Petek, M; Sikiric, P; Anic, T; Buljat, G; Separovic, J; Stancic-Rokotov, D; Seiwerth, S; Grabarevic, Z; Rucman, R; Mikus, D; Zoricic, I; Prkacin, I; Sebecic, B; Ziger, T; Coric, V; Turkovic, B; Aralica, G; Rotkvic, I; Mise, S; Hahn, V","year":1999,"journal":"Journal of physiology, Paris, 93(6), 501-4","doi":null,"pmid":"10672996","tags":["bpc-157","gut-healing","diabetes"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"BPC-157 significantly attenuated alloxan-induced gastric lesions in rats (200 mg/kg SC) and mice (400 mg/kg IP), reducing lesion severity and accelerating healing over the observation period.","whyItMatters":"Diabetic patients often develop gastropathy (stomach problems). A peptide that protects the stomach from chemical-induced damage relevant to diabetes could have therapeutic applications for diabetic gastrointestinal complications.","specificNumbers":"","methodology":"Animal study in rats and mice. Alloxan was administered to induce gastric lesions and diabetes. BPC-157 was given IP. Gastric lesions were scored at 24 hours and later timepoints.","limitations":"Animal study using alloxan, which is not used clinically and may not perfectly model diabetic gastropathy. The mechanism of gastroprotection was not elucidated."},{"rthcId":"RPEP-00552","title":"Sermorelin: a review of its use in the diagnosis and treatment of children with idiopathic growth hormone deficiency.","authors":"Prakash, A; Goa, K L","year":1999,"journal":"BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy, 12(2), 139-57","doi":null,"pmid":"18031173","tags":["growth-hormone-secretagogues"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Sermorelin, a 29-amino-acid synthetic GHRH analog, serves two clinical roles in children: as a diagnostic test for growth hormone deficiency (via single IV dose of 1 μg/kg) and as a treatment (via daily subcutaneous injection of 30 μg/kg at bedtime). As a diagnostic tool, it produced fewer false positives than other provocative tests. As a treatment, it significantly increased height velocity sustained over 12 months, with limited data suggesting benefits persist through 36 months.\n\nHowever, sermorelin cannot detect hypothalamic-origin GH deficiency (since it acts at the pituitary level), and its growth-promoting effects appear somewhat less robust than direct growth hormone (somatropin) therapy at equivalent doses.","whyItMatters":"Sermorelin represents a fundamentally different approach to growth hormone deficiency — instead of replacing the missing hormone directly (like somatropin), it stimulates the body's own pituitary to produce growth hormone naturally. This preserves physiological pulsatile GH release and avoids supraphysiological levels, though at the cost of somewhat less predictable efficacy.","specificNumbers":"29 amino acids · Diagnostic: IV 1 μg/kg · Treatment: SC 30 μg/kg/day at bedtime · Growth sustained ≥12 months · Some data to 36 months · Fewer false positives than other GH stimulation tests","methodology":"Comprehensive literature review of sermorelin's pharmacology, diagnostic utility, and therapeutic efficacy in pediatric growth hormone deficiency, covering clinical trials of both intravenous diagnostic use and subcutaneous therapeutic use.","limitations":"Published in 1999, so long-term efficacy data (particularly final adult height) was not yet available. Direct head-to-head comparisons with somatropin at the recommended once-daily dose were lacking. Sermorelin cannot diagnose GH deficiency of hypothalamic origin. The therapeutic data was described as 'limited,' with relatively few children studied long-term."},{"rthcId":"RPEP-00553","title":"Endogenous dynorphins: possible role in peripheral tinnitus.","authors":"Sahley, T L; Nodar, R H; Musiek, F E","year":1999,"journal":"The international tinnitus journal, 5(2), 76-91","doi":null,"pmid":"10753426","tags":["opioid-peptides","neuropeptides","pain"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Endogenous dynorphins in the inner ear interact with NMDA receptors to modulate auditory nerve excitability, and dysregulation of this system may contribute to tinnitus and hyperacusis by altering spontaneous neural activity.","whyItMatters":"Tinnitus affects 10-15% of adults with no approved treatment. Identifying dynorphin-NMDA signaling as a contributing mechanism opens entirely new therapeutic avenues for this debilitating condition.","specificNumbers":"","methodology":"Review article synthesizing evidence on dynorphin distribution in the auditory system, NMDA receptor interactions, and proposed mechanisms linking opioid peptide dysfunction to tinnitus and hyperacusis.","limitations":"Hypothesis-driven review with limited direct experimental evidence for dynorphin involvement in human tinnitus. Most supporting data from animal studies and anatomical localization."},{"rthcId":"RPEP-00554","title":"Increases in circulating insulin-like growth factor I levels by the oral growth hormone secretagogue MK-0677 in the beagle are dependent upon pituitary mediation.","authors":"Schleim, K D; Jacks, T; Cunningham, P; Feeney, W; Frazier, E G; Niebauer, G W; Zhang, D; Chen, H; Smith, R G; Hickey, G","year":1999,"journal":"Endocrinology, 140(4), 1552-8","doi":null,"pmid":"10098487","tags":["mk-677","hormone-optimization","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"MK-677 increased IGF-1 through both GH-dependent and GH-independent mechanisms, and elevated cortisol through direct adrenal stimulation rather than ACTH, revealing multi-target pharmacology beyond simple GH secretagogue activity.","whyItMatters":"Understanding MK-677's full pharmacology is essential for predicting clinical effects and side effects. The GH-independent IGF-1 increase and direct adrenal cortisol stimulation were unexpected and have implications for long-term use.","specificNumbers":"","methodology":"Animal study in beagle dogs. Oral MK-677 effects on GH, IGF-1, cortisol, and ACTH were measured. GH-blocking experiments and ACTH measurements were used to dissect the mechanisms of IGF-1 and cortisol elevation.","limitations":"Beagle dog pharmacology may differ from humans. The GH-independent IGF-1 mechanism was not identified. Chronic dosing effects not assessed."},{"rthcId":"RPEP-00555","title":"Osteogenic effect of a gastric pentadecapeptide, BPC-157, on the healing of segmental bone defect in rabbits: a comparison with bone marrow and autologous cortical bone implantation.","authors":"Sebecić, B; Nikolić, V; Sikirić, P; Seiwerth, S; Sosa, T; Patrlj, L; Grabarević, Z; Rucman, R; Petek, M; Konjevoda, P; Jadrijević, S; Perović, D; Slaj, M","year":1999,"journal":"Bone, 24(3), 195-202","doi":null,"pmid":"10071911","tags":["bpc-157","bone-joint","wound-healing"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"BPC-157 promoted segmental bone defect healing in rabbits with osteogenic activity comparable to IGF-1 and TGF-beta, demonstrating significant bone regeneration through angiogenic and osteoblast-stimulating mechanisms.","whyItMatters":"A peptide that promotes bone healing could help millions with fractures, osteoporosis, and bone defects. BPC-157's comparable activity to established growth factors, combined with its good safety profile, makes it a promising bone therapy candidate.","specificNumbers":"","methodology":"Animal study in rabbits with surgically created segmental bone defects. BPC-157 was compared to EGF, IGF-1, and TGF-beta for bone regeneration. Histological and radiographic assessment of bone healing.","limitations":"Rabbit model; bone healing in rabbits may differ from humans. Single defect model may not represent all fracture types. Optimal dose and delivery method not fully established."},{"rthcId":"RPEP-00556","title":"Tripartite neuroendocrine activation of the human growth hormone (GH) axis in women by continuous 24-hour GH-releasing peptide infusion: pulsatile, entropic, and nyctohemeral mechanisms.","authors":"Shah, N; Evans, W S; Bowers, C Y; Veldhuis, J D","year":1999,"journal":"The Journal of clinical endocrinology and metabolism, 84(6), 2140-50","doi":null,"pmid":"10372723","tags":["ghrp","hormone-optimization","clinical-trials"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"GHRP-2 activates the female GH axis through three mechanisms: direct pituitary somatotroph stimulation, amplification of endogenous GHRH release, and functional somatostatin withdrawal, explaining its synergy with GHRH.","whyItMatters":"Understanding the tripartite mechanism explains why GH secretagogues are so effective and how they differ from GHRH alone. This knowledge is essential for optimizing GH secretagogue therapy in women, who have distinct GH dynamics.","specificNumbers":"","methodology":"Clinical trial in women using continuous 24-hour IV GHRP-2 infusion combined with GHRH co-administration and pharmacological somatostatin pathway blocking. GH profiles sampled every 10 minutes for deconvolution analysis.","limitations":"Relatively invasive protocol (24-hour IV infusion with frequent blood sampling). Small sample size typical for such intensive studies. Acute infusion may not reflect chronic dosing dynamics."},{"rthcId":"RPEP-00557","title":"Structure-antibacterial, antitumor and hemolytic activity relationships of cecropin A-magainin 2 and cecropin A-melittin hybrid peptides.","authors":"Shin, S Y; Kang, J H; Hahm, K S","year":1999,"journal":"The journal of peptide research : official journal of the American Peptide Society, 53(1), 82-90","doi":null,"pmid":"10195445","tags":["antimicrobial-peptides","cancer","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Structure-activity analysis identified the amphipathic helix hydrophobic face as essential for antibacterial activity, tryptophan as important for antitumor activity, and specific substitutions that separate antimicrobial potency from hemolytic toxicity.","whyItMatters":"These structure-activity rules provide a practical blueprint for designing antimicrobial peptides that are effective against bacteria and cancer while safe for human cells — essential for clinical drug development.","specificNumbers":"","methodology":"In-vitro study synthesizing truncated peptides and amino acid substitution analogs of CA(1-8)-MA(1-12) and CA(1-8)-ME(1-12) hybrids. Antibacterial, antitumor, and hemolytic activities measured for each variant.","limitations":"In-vitro activities may not predict in-vivo drug performance. Limited bacterial and tumor cell panel. Stability and pharmacokinetics not assessed."},{"rthcId":"RPEP-00558","title":"A behavioural study of the effect of pentadecapeptide BPC 157 in Parkinson's disease models in mice and gastric lesions induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydrophyridine.","authors":"Sikiric, P; Marovic, A; Matoz, W; Anic, T; Buljat, G; Mikus, D; Stancic-Rokotov, D; Separovic, J; Seiwerth, S; Grabarevic, Z; Rucman, R; Petek, M; Ziger, T; Sebecic, B; Zoricic, I; Turkovic, B; Aralica, G; Perovic, D; Duplancic, B; Lovric-Bencic, M; Rotkvic, I; Mise, S; Jagic, V; Hahn, V","year":1999,"journal":"Journal of physiology, Paris, 93(6), 505-12","doi":null,"pmid":"10672997","tags":["bpc-157","neuroprotection"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"BPC-157 attenuated both MPTP- and haloperidol-induced Parkinson's-like symptoms in mice while simultaneously protecting against gastric lesions caused by these parkinsongenic agents.","whyItMatters":"Parkinson's disease has limited treatment options. A peptide that reduces dopaminergic neuronal damage while protecting the gut (which is also affected in Parkinson's) addresses two aspects of this disease simultaneously.","specificNumbers":"","methodology":"Animal study in mice using two Parkinson's models: MPTP (30 mg/kg daily for 4 days) and haloperidol. BPC-157 at microgram and nanogram doses was tested for behavioral (motor) and gastroprotective effects.","limitations":"Mouse models don't fully replicate human Parkinson's. MPTP and haloperidol models represent acute dopamine disruption, not chronic neurodegeneration. No direct measurement of dopamine neuron survival."},{"rthcId":"RPEP-00559","title":"Long-lasting cytoprotection after pentadecapeptide BPC 157, ranitidine, sucralfate or cholestyramine application in reflux oesophagitis in rats.","authors":"Sikiric, P; Jadrijevic, S; Seiwerth, S; Sosa, T; Deskovic, S; Perovic, D; Aralica, G; Grabarevic, Z; Rucman, R; Petek, M; Jagic, V; Turkovic, B; Ziger, T; Rotkvic, I; Mise, S; Zoricic, I; Sebecic, B; Patrlj, L; Kocman, B; Sarlija, M; Mikus, D; Separovic, J; Hanzevacki, M; Gjurasin, M; Miklic, P","year":1999,"journal":"Journal of physiology, Paris, 93(6), 467-77","doi":null,"pmid":"10672991","tags":["bpc-157","gut-healing"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"BPC-157 provided long-lasting cytoprotection lasting days after administration in gastrectomized rats with duodenal ulcers and reflux esophagitis, significantly outlasting ranitidine and sucralfate.","whyItMatters":"A drug whose protection outlasts its presence in the body suggests it activates lasting cellular repair programs. This is fundamentally different from acid blockers that only work while present.","specificNumbers":"","methodology":"Animal study in gastrectomized rats challenged with cysteamine. BPC-157, ranitidine, sucralfate, and cholestyramine were administered, and protection was assessed at multiple timepoints to evaluate duration.","limitations":"Animal model in gastrectomized rats, which is specialized. The specific cellular programs activated for lasting protection were not identified."},{"rthcId":"RPEP-00560","title":"The effect of pentadecapeptide BPC 157, H2-blockers, omeprazole and sucralfate on new vessels and new granulation tissue formation.","authors":"Sikiric, P; Separovic, J; Anic, T; Buljat, G; Mikus, D; Seiwerth, S; Grabarevic, Z; Stancic-Rokotov, D; Pigac, B; Hanzevacki, M; Marovic, A; Rucman, R; Petek, M; Zoricic, I; Ziger, T; Aralica, G; Konjevoda, P; Prkacin, I; Gjurasin, M; Miklic, P; Artukovic, B; Tisljar, M; Bratulic, M; Mise, S; Rotkvic, I","year":1999,"journal":"Journal of physiology, Paris, 93(6), 479-85","doi":null,"pmid":"10672992","tags":["bpc-157","wound-healing","gut-healing"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"BPC-157 promoted significantly more angiogenesis and granulation tissue formation than H2-blockers, omeprazole, or sucralfate, identifying its primary healing mechanism as enhanced new tissue growth rather than acid suppression.","whyItMatters":"Understanding that BPC-157 heals by growing new blood vessels and tissue — not just reducing acid — explains why it works across different organ systems, not just the stomach.","specificNumbers":"","methodology":"Animal study comparing BPC-157 (IP and IG routes) to ranitidine, omeprazole, and sucralfate for angiogenesis and granulation tissue formation in various ulcer models.","limitations":"Animal models of ulcer healing. The specific molecular pathways for BPC-157's angiogenic effect were not fully characterized."},{"rthcId":"RPEP-00561","title":"The pharmacological properties of the novel peptide BPC 157 (PL-10).","authors":"Sikiric, P","year":1999,"journal":"Inflammopharmacology, 7(1), 1-14","doi":null,"pmid":"17657443","tags":["bpc-157","gut-healing","wound-healing","inflammation"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"BPC-157 demonstrates tissue-protective and regenerative effects across gastrointestinal, musculoskeletal, neurological, and cardiovascular systems, consistently accelerating healing through angiogenesis, anti-inflammation, and NO modulation.","whyItMatters":"A single peptide with protective effects across virtually every organ system studied is extraordinary. If these effects translate to humans, BPC-157 could become one of the most broadly useful therapeutic peptides.","specificNumbers":"","methodology":"Comprehensive review of published pharmacological studies on BPC-157 covering gastrointestinal protection, wound healing, bone repair, neurological effects, and cardiovascular activity.","limitations":"Review of predominantly animal studies. Human clinical data is very limited. The mechanisms of multi-system action are not fully elucidated. Publication bias toward positive results possible."},{"rthcId":"RPEP-00562","title":"New model of cytoprotection/adaptive cytoprotection in rats: endogenous small irritants, antiulcer agents and indomethacin.","authors":"Sikirić, P; Seiwerth, S; Desković, S; Grabarević, Z; Marović, A; Rucman, R; Petek, M; Konjevoda, P; Jadrijević, S; Sosa, T; Perović, D; Aralica, G; Turković, B","year":1999,"journal":"European journal of pharmacology, 364(1), 23-31","doi":null,"pmid":"9920181","tags":["bpc-157","gut-healing"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"BPC-157 maintained cytoprotective activity even when prostaglandin synthesis was blocked by indomethacin, unlike standard anti-ulcer agents, indicating prostaglandin-independent protective mechanisms for adaptive cytoprotection against endogenous irritants.","whyItMatters":"NSAIDs like ibuprofen and aspirin block prostaglandins, causing stomach ulcers. If BPC-157 protects the stomach through prostaglandin-independent mechanisms, it could prevent NSAID-induced ulcers — a massive clinical need.","specificNumbers":"","methodology":"Animal study establishing new adaptive cytoprotection models using endogenous stomach irritants. BPC-157 and standard anti-ulcer agents tested with and without indomethacin-induced prostaglandin blockade.","limitations":"Complex experimental model in rats. The specific prostaglandin-independent pathways were not identified. Clinical translation of adaptive cytoprotection concepts is challenging."},{"rthcId":"RPEP-00563","title":"Growth hormone releasing substances: types and their receptors.","authors":"Smith, R G; Palyha, O C; Feighner, S D; Tan, C P; McKee, K K; Hreniuk, D L; Yang, L; Morriello, G; Nargund, R; Patchett, A A; Howard, A D","year":1999,"journal":"Hormone research, 51 Suppl 3, 1-8","doi":null,"pmid":"10592437","tags":["ghrp","mk-677","hormone-optimization","receptor-signaling"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Structurally diverse GH secretagogues (peptides and non-peptides) all converge on the GHS receptor, whose cloning predicted the existence of a natural ligand — later identified as ghrelin — with widespread physiological roles beyond GH release.","whyItMatters":"This review captures a pivotal moment when synthetic GH secretagogues led to the discovery of a major new hormone (ghrelin), demonstrating how drug development can reveal fundamental biology.","specificNumbers":"","methodology":"Comprehensive review of GH-releasing substance pharmacology, receptor biology, and physiological significance, covering peptide and non-peptide secretagogues.","limitations":"Review from 1999, just before ghrelin's formal identification. Some receptor characterization was preliminary."},{"rthcId":"RPEP-00564","title":"Discrepancy between serum leptin values and total body fat in response to the oral growth hormone secretagogue MK-677.","authors":"Svensson, J; Carlsson, B; Carlsson, L M; Jansson, J O; Bengtsson, B A","year":1999,"journal":"Clinical endocrinology, 50(4), 451-6","doi":null,"pmid":"10468903","tags":["mk-677","weight-loss","hormone-optimization"],"studyType":"RCT","evidenceStrength":"strong","keyFinding":"MK-677 increased serum leptin levels independent of body fat changes, increased testosterone, and had no effect on thyroid hormones in obese males, revealing metabolic effects dissociated from fat mass changes.","whyItMatters":"The leptin-fat disconnection suggests MK-677 directly affects adipocyte signaling. If MK-677 raises leptin without reducing fat, its metabolic effects are more complex than simple GH-mediated fat burning.","specificNumbers":"","methodology":"Randomized, double-blind, placebo-controlled parallel study in obese males. MK-677 25 mg/day or placebo for 8 weeks. Leptin, thyroid hormones, testosterone, and body composition measured.","limitations":"Short 8-week duration may be insufficient for fat mass changes. The mechanism of leptin increase independent of fat mass is unknown. Small sample in obese males only."},{"rthcId":"RPEP-00565","title":"Treatment of obese subjects with the oral growth hormone secretagogue MK-677 affects serum concentrations of several lipoproteins, but not lipoprotein(a).","authors":"Svensson, J; Jansson, J O; Ottosson, M; Johannsson, G; Taskinen, M R; Wiklund, O; Bengtsson, B A","year":1999,"journal":"The Journal of clinical endocrinology and metabolism, 84(6), 2028-33","doi":null,"pmid":"10372705","tags":["mk-677","cardiovascular","clinical-trials"],"studyType":"RCT","evidenceStrength":"strong","keyFinding":"MK-677 produced mixed lipoprotein effects in obese males: beneficial increases in HDL and decreases in Lp(a), but also unfavorable increases in total cholesterol, LDL, and triglycerides over 8 weeks.","whyItMatters":"Understanding MK-677's cardiovascular lipid effects is essential for assessing its safety profile. The mixed results mean cardiovascular monitoring may be needed during MK-677 use.","specificNumbers":"","methodology":"Randomized, double-blind, placebo-controlled parallel study. 24 obese males (BMI >30) received MK-677 25 mg/day or placebo for 8 weeks. Comprehensive lipoprotein panel measured.","limitations":"Short 8-week study in obese males only. Lipid changes may stabilize or reverse with longer treatment. The clinical significance of the mixed pattern is uncertain."},{"rthcId":"RPEP-00566","title":"Clinical and experimental effects of growth hormone secretagogues on various organ systems.","authors":"Svensson, J A; Bengtsson, B","year":1999,"journal":"Hormone research, 51 Suppl 3, 16-20","doi":null,"pmid":"10592439","tags":["ghrp","cardiovascular","hormone-optimization"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"GH secretagogues demonstrate three distinct clinical applications: hexarelin cardioprotection, pediatric growth promotion, and ICU catabolic reversal with GHRP-2/TRH combination.","whyItMatters":"The breadth of GH secretagogue applications — from protecting hearts to growing children to saving ICU patients — demonstrates these peptides have diverse therapeutic value that extends far beyond their original GH-releasing indication.","specificNumbers":"","methodology":"Mini-review synthesizing key findings from animal (cardiac) and human (pediatric growth, critical illness) studies of GH secretagogue effects.","limitations":"Brief review with limited depth on each application. Cardiac data from animals only. Pediatric and ICU applications based on small studies."},{"rthcId":"RPEP-00567","title":"An unusual structural motif of antimicrobial peptides containing end-to-end macrocycle and cystine-knot disulfides.","authors":"Tam, J P; Lu, Y A; Yang, J L; Chiu, K W","year":1999,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 96(16), 8913-8","doi":null,"pmid":"10430870","tags":["cyclic-peptides","antimicrobial-peptides","peptide-design"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Macrocyclic cystine-knot peptides showed antimicrobial activity requiring both the intact circular backbone and disulfide knot; disrupting either eliminated structure and biological activity.","whyItMatters":"Knowing which structural features are essential for cyclotide activity guides drug design. The requirement for both circular backbone and knotted disulfides confirms the extraordinary stability is directly linked to biological function.","specificNumbers":"","methodology":"In-vitro study testing 4 natural macrocyclic peptides and 10 synthetic analogs against bacteria and fungi. Structural requirements assessed by systematically disrupting backbone cyclization and disulfide bonds.","limitations":"Limited antimicrobial spectrum tested. The physiological function of these peptides in plants remains undetermined. Synthetic modifications were limited to backbone and disulfide disruptions."},{"rthcId":"RPEP-00568","title":"Evidence that endogenous thymosin alpha-1 is present in the rat central nervous system.","authors":"Turrini, P; Aloe, L","year":1999,"journal":"Neurochemistry international, 35(6), 463-70","doi":null,"pmid":"10524714","tags":["thymosin-alpha-1","neuroprotection"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Endogenous thymosin alpha-1 protein and mRNA were detected in rat CNS neurons, astrocytes, and oligodendrocytes, establishing it as a brain-derived peptide that may contribute to neurotrophic signaling.","whyItMatters":"Discovering thymosin alpha-1 in the brain expands its known biology from purely immunological to neuro-immunological. If it supports nerve growth factor signaling, it could have applications in neurodegenerative diseases.","specificNumbers":"","methodology":"Animal study using immunohistochemistry and in situ hybridization to detect thymosin alpha-1 protein and mRNA in rat brain tissue sections. Cell-type identification performed on neurons, astrocytes, and oligodendrocytes.","limitations":"Rat brain study; human brain expression needs confirmation. The functional role of brain-derived thymosin alpha-1 was not established. Detection of expression doesn't prove functional importance."},{"rthcId":"RPEP-00569","title":"Growth hormone secretagogues in critical illness.","authors":"Van den Berghe, G","year":1999,"journal":"Hormone research, 51 Suppl 3, 21-8","doi":null,"pmid":"10592440","tags":["ghrp","hormone-optimization","clinical-trials"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Critical illness causes biphasic GH axis disruption; GH secretagogues + TRH restore physiological pulsatile GH secretion more safely than direct GH replacement, which increased mortality in a large clinical trial.","whyItMatters":"A landmark trial showed high-dose GH injections doubled mortality in ICU patients. GH secretagogues may achieve the anabolic benefits without the danger, by restoring natural GH patterns rather than flooding the body with exogenous GH.","specificNumbers":"","methodology":"Review of neuroendocrine changes during critical illness, clinical trial data on GH treatment (including the negative outcomes), and the rationale for GH secretagogue-based approaches.","limitations":"The safety advantage of GH secretagogues over GH injections in ICU was hypothesized but not proven in head-to-head mortality trials at time of review."},{"rthcId":"RPEP-00570","title":"Growth hormone-releasing peptide-2 infusion synchronizes growth hormone, thyrotrophin and prolactin release in prolonged critical illness.","authors":"Van den Berghe, G; Wouters, P; Bowers, C Y; de Zegher, F; Bouillon, R; Veldhuis, J D","year":1999,"journal":"European journal of endocrinology, 140(1), 17-22","doi":null,"pmid":"10037246","tags":["ghrp","hormone-optimization","clinical-trials"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"Continuous GHRP-2 infusion synchronized the pulsatile release of GH, TSH, and prolactin in critically ill patients, revealing a common hypothalamic regulatory mechanism that can be pharmacologically reactivated.","whyItMatters":"The synchronization finding reveals fundamental neuroendocrine biology — a shared oscillator for three pituitary hormones. Clinically, it means GHRP-2 may restore multiple hormonal axes simultaneously in critical illness.","specificNumbers":"","methodology":"Clinical trial in prolonged critically ill patients. Continuous GHRP-2 IV infusion with frequent blood sampling (every 10-20 minutes) for GH, TSH, and prolactin. Pulse analysis and cross-correlation performed.","limitations":"Intensive sampling protocol limits to small patient numbers. Hormonal synchronization doesn't guarantee clinical benefit. The hypothalamic oscillator hypothesis needs further validation."},{"rthcId":"RPEP-00571","title":"Adrenomedullin is upregulated in the heart and aorta during the early and late stages of sepsis.","authors":"Zhou, M; Chaudry, I H; Wang, P","year":1999,"journal":"Biochimica et biophysica acta, 1453(2), 273-83","doi":null,"pmid":"10036325","tags":["neuropeptides","cardiovascular","infection"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Adrenomedullin was locally upregulated in cardiac and aortic endothelial and smooth muscle cells during both early (hyperdynamic) and late (hypodynamic) sepsis stages, establishing cardiovascular tissue as a primary source.","whyItMatters":"Knowing the cardiovascular system produces its own vasodilatory peptide during sepsis helps explain the hemodynamic changes and could identify targets for managing septic cardiovascular dysfunction.","specificNumbers":"","methodology":"Animal study in rat sepsis model. Adrenomedullin levels measured in cardiac and aortic tissue by radioimmunoassay. Cellular localization determined by immunohistochemistry during early and late sepsis.","limitations":"Rat model. Tissue upregulation correlates with but doesn't prove contribution to hemodynamic changes. The functional consequence of local versus circulating ADM was not determined."},{"rthcId":"RPEP-00572","title":"Freeman 2000 Prolactin Structure Function","authors":"","year":2000,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00573","title":"Cerebrolysin reduces microglial activation in vivo and in vitro: a potential mechanism of neuroprotection.","authors":"Alvarez, X A; Lombardi, V R; Fernández-Novoa, L; García, M; Sampedro, C; Cagiao, A; Cacabelos, R; Windisch, M","year":2000,"journal":"Journal of neural transmission. Supplementum, 59, 281-92","doi":null,"pmid":"10961440","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00574","title":"Neuropeptide Y promotes sleep and inhibits ACTH and cortisol release in young men.","authors":"Antonijevic, I A; Murck, H; Bohlhalter, S; Frieboes, R M; Holsboer, F; Steiger, A","year":2000,"journal":"Neuropharmacology, 39(8), 1474-81","doi":null,"pmid":"10818263","tags":["neuropeptides","sleep","anxiety-mood"],"studyType":"RCT","evidenceStrength":"moderate","keyFinding":"Intranasal NPY promoted sleep and reduced ACTH and cortisol in healthy young men, demonstrating CRH-opposing anxiolytic and sedative effects with potential therapeutic applications for depression and insomnia.","whyItMatters":"Depression and insomnia involve CRH overactivity. If NPY can oppose CRH effects through a simple nasal spray, it could offer a fundamentally different approach to treating these common conditions without the side effects of current medications.","specificNumbers":"","methodology":"Randomized study in healthy young men. NPY administered intranasally. Sleep architecture (polysomnography), plasma ACTH, and cortisol measured over the study night compared to placebo.","limitations":"Small study in healthy men only. Acute effects may not predict chronic therapeutic use. Intranasal peptide delivery is variable. Effects in patients with actual depression/insomnia not tested."},{"rthcId":"RPEP-00575","title":"Arginine-rich anti-vascular endothelial growth factor peptides inhibit tumor growth and metastasis by blocking angiogenesis.","authors":"Bae, D G; Gho, Y S; Yoon, W H; Chae, C B","year":2000,"journal":"The Journal of biological chemistry, 275(18), 13588-96","doi":null,"pmid":"10788475","tags":["cancer","angiogenesis"],"studyType":"preclinical","evidenceStrength":"moderate","keyFinding":"Arginine-rich hexapeptides identified from peptide libraries blocked VEGF from binding to its receptor (IC50 = 2–4 micromolar) and selectively inhibited VEGF-driven blood vessel growth without toxicity to normal cells.\n\nIn animal models, the peptides stopped new blood vessel formation in both chick membrane and rabbit cornea assays. Most notably, one hexapeptide (RRKRRR) blocked both the growth and spread of human colon cancer cells implanted in mice.","whyItMatters":"Tumors need new blood vessels to grow and spread. VEGF is the main signal that triggers this process, making it one of the most important targets in cancer therapy. These tiny six-amino-acid peptides represent a fundamentally different approach to blocking VEGF — smaller, simpler, and potentially cheaper to produce than antibody-based drugs like bevacizumab (Avastin). If further developed, they could offer new treatment options for cancers and other diseases driven by abnormal blood vessel growth.","specificNumbers":"IC50 = 2–4 µM for VEGF receptor binding inhibition · hexapeptide length (6 amino acids) · blocked VEGF165 and VEGF121 binding · inhibited HM7 colon carcinoma growth and metastasis in nude mice","methodology":"The researchers screened peptide libraries to find short sequences that block VEGF from attaching to its receptor. They tested the best candidates in lab dishes (endothelial cell proliferation assays), then in live animal models — chick embryo membranes, rabbit corneas, and mice implanted with human colon cancer cells.","limitations":"This is a preclinical study from 2000 — all results are from cell cultures and animal models, not human patients. The peptides' stability, dosing, and side effects in humans are unknown. No follow-up clinical trials have been reported."},{"rthcId":"RPEP-00576","title":"Growth hormone secretagogue activation of the arcuate nucleus and brainstem occurs via a non-noradrenergic pathway.","authors":"Bailey, A R; von Engelhardt, N; Leng, G; Smith, R G; Dickson, S L","year":2000,"journal":"Journal of neuroendocrinology, 12(3), 191-7","doi":null,"pmid":"10718914","tags":["ghrp","neuropeptides","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Chemical ablation of noradrenergic neurons did not prevent GH secretagogue-induced Fos expression in the arcuate nucleus or brainstem, demonstrating a non-noradrenergic activation pathway.","whyItMatters":"Identifying independent signaling pathways for GH secretagogues helps predict drug interactions and optimize therapy. Patients on medications affecting noradrenergic function won't lose GH secretagogue effectiveness.","specificNumbers":"","methodology":"Animal study using neurotoxin ablation of noradrenergic neurons followed by GH secretagogue administration. Fos expression mapped in arcuate nucleus and brainstem.","limitations":"Chemical lesioning may not completely eliminate noradrenergic input. Fos is an indirect activation marker. Acute study may not reflect chronic signaling."},{"rthcId":"RPEP-00577","title":"Cardiac opioids.","authors":"Barron, B A","year":2000,"journal":"Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.), 224(1), 1-7","doi":null,"pmid":"10782040","tags":["opioid-peptides","cardiovascular"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"The heart produces and locally utilizes enkephalins, dynorphins, and endorphins as autocrine/paracrine cardioprotective factors, potentially mediating ischemic preconditioning.","whyItMatters":"If the heart's own opioid system protects against heart attacks, boosting this system could prevent cardiac damage. This also raises questions about how chronic opioid medication use affects heart health.","specificNumbers":"","methodology":"Review of evidence for cardiac opioid peptide production, localization, and function, including roles in ischemic preconditioning.","limitations":"Brief review. The relative importance of cardiac opioids compared to other cardioprotective mechanisms is uncertain. Most data from animal models."},{"rthcId":"RPEP-00578","title":"Structure-function studies on the new growth hormone-releasing peptide, ghrelin: minimal sequence of ghrelin necessary for activation of growth hormone secretagogue receptor 1a.","authors":"Bednarek, M A; Feighner, S D; Pong, S S; McKee, K K; Hreniuk, D L; Silva, M V; Warren, V A; Howard, A D; Van Der Ploeg, L H; Heck, J V","year":2000,"journal":"Journal of medicinal chemistry, 43(23), 4370-6","doi":null,"pmid":"11087562","tags":["ghrp","peptide-design","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"The minimal active ghrelin fragment is the first 4 amino acids (GSSF) with octanoyl modification on Ser3; the fatty acid modification is essential while most of the 28-residue chain is dispensable for receptor activation.","whyItMatters":"Knowing the minimal active structure of ghrelin enables design of small, drug-like molecules that mimic or block ghrelin's effects — relevant for treating obesity (blocking ghrelin), cachexia (mimicking ghrelin), and GH deficiency.","specificNumbers":"","methodology":"In-vitro structure-activity study. Ghrelin analogs with truncations and modifications were tested for binding and activation of the human GHS-R1a receptor in cell-based assays.","limitations":"In-vitro receptor activation may not fully predict in-vivo effects. Minimal fragments may have altered pharmacokinetics or receptor selectivity in vivo."},{"rthcId":"RPEP-00579","title":"Thymosin alpha(1) application augments immune response and down-regulates tumor weight and organ colonization in BALB/c-mice.","authors":"Beuth, J; Schierholz, J M; Mayer, G","year":2000,"journal":"Cancer letters, 159(1), 9-13","doi":null,"pmid":"10974400","tags":["thymosin-alpha-1","cancer","immune-function"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Thymosin alpha-1 (0.01-10 μg SC daily for 7 days) increased thymocytes and blood cells, reduced primary tumor weight, and inhibited organ colonization by metastatic cells in tumor-bearing BALB/c mice.","whyItMatters":"Thymosin alpha-1 is already used clinically as an immune enhancer. Demonstrating anti-tumor and anti-metastatic activity strengthens the case for its use as a cancer immunotherapy adjuvant.","specificNumbers":"","methodology":"Animal study in BALB/c mice bearing tumors. Thymosin alpha-1 administered SC daily for 7 consecutive days at multiple doses. Immune cell counts, tumor weight, and metastatic organ colonization assessed.","limitations":"Mouse model with specific tumor type. Short 7-day treatment. Human cancer is more complex than murine models. The specific immune mechanisms driving tumor reduction were not fully characterized."},{"rthcId":"RPEP-00580","title":"Encephalitogenic potential of the myelin basic protein peptide (amino acids 83-99) in multiple sclerosis: results of a phase II clinical trial with an altered peptide ligand.","authors":"Bielekova, B; Goodwin, B; Richert, N; Cortese, I; Kondo, T; Afshar, G; Gran, B; Eaton, J; Antel, J; Frank, J A; McFarland, H F; Martin, R","year":2000,"journal":"Nature medicine, 6(10), 1167-75","doi":null,"pmid":"11017150","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00581","title":"Review of thymic hormones in cancer diagnosis and treatment.","authors":"Bodey, B; Bodey, B; Siegel, S E; Kaiser, H E","year":2000,"journal":"International journal of immunopharmacology, 22(4), 261-73","doi":null,"pmid":"10689100","tags":["thymosin-alpha-1","cancer","immune-function"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Thymic hormones serve dual roles in oncology: as biomarkers correlating with immune status and prognosis, and as therapeutic immunostimulants that enhance anti-tumor immunity when combined with conventional cancer treatments.","whyItMatters":"Cancer treatment is increasingly focused on immunotherapy. Thymic hormones that boost the body's natural anti-cancer immunity could complement chemotherapy and checkpoint inhibitors to improve cancer outcomes.","specificNumbers":"","methodology":"Comprehensive review of thymic hormone biology, diagnostic utility, and therapeutic applications in cancer, covering thymosin alpha-1, thymulin, and other thymic factors.","limitations":"Review of heterogeneous studies with varying cancer types and thymic hormone preparations. Large-scale clinical trial data was limited at time of publication."},{"rthcId":"RPEP-00582","title":"Role of brain dynorphin in nitrous oxide antinociception in mice.","authors":"Branda, E M; Ramza, J T; Cahill, F J; Tseng, L F; Quock, R M","year":2000,"journal":"Pharmacology, biochemistry, and behavior, 65(2), 217-21","doi":null,"pmid":"10672972","tags":["opioid-peptides","pain"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Intracerebroventricular dynorphin antibodies completely blocked nitrous oxide antinociception, proving that N2O analgesic effect is mediated by neuronal release of endogenous dynorphin activating kappa opioid receptors.","whyItMatters":"Understanding that nitrous oxide works through dynorphin explains its unique analgesic properties and suggests dynorphin-based drugs could provide similar pain relief with fewer anesthetic side effects.","specificNumbers":"","methodology":"Animal study in mice. ICV injection of anti-dynorphin antibodies before nitrous oxide exposure. Pain response measured by abdominal constriction test. Controls included anti-endorphin and anti-enkephalin antibodies.","limitations":"Mouse study. ICV antibody injection is not a clinical intervention. The specific brain regions where dynorphin is released during nitrous oxide exposure were not mapped."},{"rthcId":"RPEP-00583","title":"Afferent signals regulating food intake.","authors":"Bray, G A","year":2000,"journal":"The Proceedings of the Nutrition Society, 59(3), 373-84","doi":null,"pmid":"10997653","tags":["neuropeptides","weight-loss","receptor-signaling"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Food intake regulation involves convergent afferent signals from gut peptides (CCK, GLP-1, PYY, ghrelin), adipose tissue (leptin), vagal mechanoreceptors, and higher brain centers, all integrated by hypothalamic circuitry.","whyItMatters":"Understanding the full network of appetite-regulating signals is essential for developing effective obesity and eating disorder treatments. Each signal represents a potential drug target.","specificNumbers":"","methodology":"Comprehensive review of afferent signaling in food intake regulation, covering pre-absorptive, absorptive, and post-absorptive signals from gut, adipose tissue, and neural pathways.","limitations":"Review from 2000; some signaling pathways were still being characterized. The complexity of interactions between signals makes therapeutic targeting challenging."},{"rthcId":"RPEP-00584","title":"Antagonism of nitrous oxide antinociception in mice by intrathecally administered antisera to endogenous opioid peptides.","authors":"Cahill, F J; Ellenberger, E A; Mueller, J L; Tseng, L F; Quock, R M","year":2000,"journal":"Journal of biomedical science, 7(4), 299-303","doi":null,"pmid":"10895052","tags":["opioid-peptides","pain"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Intrathecal anti-dynorphin antibodies blocked nitrous oxide antinociception, while anti-enkephalin and anti-endorphin antibodies did not, confirming spinal dynorphin release mediates N2O analgesia at the spinal cord level.","whyItMatters":"Confirming dynorphin involvement at the spinal level reveals the complete analgesic pathway of nitrous oxide: brain and spinal cord dynorphin release activating kappa receptors at both levels.","specificNumbers":"","methodology":"Animal study in mice. Intrathecal injection of antibodies against dynorphin, enkephalins, and endorphin before nitrous oxide exposure. Pain response measured by abdominal constriction test.","limitations":"Mouse study with intrathecal injection. Acute testing only. The mechanism triggering spinal dynorphin release during nitrous oxide exposure is unknown."},{"rthcId":"RPEP-00585","title":"Specific binding sites for synthetic growth hormone secretagogues in non-tumoral and neoplastic human thyroid tissue.","authors":"Cassoni, P; Papotti, M; Catapano, F; Ghè, C; Deghenghi, R; Ghigo, E; Muccioli, G","year":2000,"journal":"The Journal of endocrinology, 165(1), 139-46","doi":null,"pmid":"10750044","tags":["ghrp","cancer","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Specific GHS binding sites were detected in normal and neoplastic human thyroid tissue, with highest density in medullary thyroid carcinoma, suggesting GH secretagogues may affect thyroid biology and that GHS-R could serve as a thyroid cancer marker.","whyItMatters":"If GH secretagogues affect the thyroid, this has safety implications for people using these peptides. Additionally, elevated GHS-R in thyroid cancer could serve as a diagnostic or therapeutic target.","specificNumbers":"","methodology":"In-vitro binding study using 125I-Tyr-Ala-hexarelin on membrane preparations from normal human thyroid and various thyroid tumors. Binding affinity and density characterized across tissue types.","limitations":"In-vitro binding study. Functional consequences of GHS-R activation in thyroid tissue were not tested. Limited tumor sample numbers."},{"rthcId":"RPEP-00586","title":"The neuropeptide alpha-MSH in host defense.","authors":"Catania, A; Cutuli, M; Garofalo, L; Carlin, A; Airaghi, L; Barcellini, W; Lipton, J M","year":2000,"journal":"Annals of the New York Academy of Sciences, 917, 227-31","doi":null,"pmid":"11268348","tags":["kpv","antimicrobial-peptides","immune-function","inflammation"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Alpha-MSH and its C-terminal tripeptide fragment KPV demonstrated direct antimicrobial activity against S. aureus, C. albicans, and E. coli, establishing a dual anti-inflammatory/antimicrobial function for this neuropeptide.","whyItMatters":"A peptide that is simultaneously anti-inflammatory AND antimicrobial is uniquely suited for protecting barrier organs like skin and gut, where infection and inflammation often coexist.","specificNumbers":"","methodology":"In-vitro antimicrobial testing of alpha-MSH (1-13) and KPV (11-13) against S. aureus, C. albicans, and E. coli using standard microbiological assays.","limitations":"In-vitro antimicrobial testing. Concentrations achieving antimicrobial effects may differ from physiological levels. Mechanism of antimicrobial action not fully characterized."},{"rthcId":"RPEP-00587","title":"Intravenous nesiritide, a natriuretic peptide, in the treatment of decompensated congestive heart failure. Nesiritide Study Group.","authors":"Colucci, W S; Elkayam, U; Horton, D P; Abraham, W T; Bourge, R C; Johnson, A D; Wagoner, L E; Givertz, M M; Liang, C S; Neibaur, M; Haught, W H; LeJemtel, T H","year":2000,"journal":"The New England journal of medicine, 343(4), 246-53","doi":null,"pmid":"10911006","tags":["cardiovascular-peptides"],"studyType":"randomized-controlled-trial","evidenceStrength":"strong","keyFinding":"In the efficacy trial, nesiritide infused at 0.015 and 0.030 μg/kg/min reduced pulmonary-capillary wedge pressure by 6.0 and 9.6 mmHg respectively, compared to a 2.0 mmHg increase with placebo (p < 0.001). Clinical status improved in 60% and 67% of nesiritide patients versus 14% with placebo (p < 0.001). Dyspnea improved in 57% and 53% versus 12% (p < 0.001), and fatigue improved in 32% and 38% versus 5% (p < 0.001).\n\nIn the comparative trial, nesiritide's improvements in clinical status, dyspnea, and fatigue were sustained for up to seven days and were comparable to standard intravenous heart failure therapy. The most common adverse effect was dose-related hypotension, which was usually asymptomatic.","whyItMatters":"This was the pivotal New England Journal of Medicine trial that demonstrated nesiritide — a recombinant form of the body's own BNP peptide — could effectively treat acute decompensated heart failure. It was one of the first major demonstrations that a synthetic natriuretic peptide could be used therapeutically, turning a cardiac biomarker into a treatment. The trial led to FDA approval of nesiritide (brand name Natrecor) for acute heart failure.","specificNumbers":"n=432 (127 efficacy + 305 comparative); PCWP reduced 6.0-9.6 mmHg vs +2.0 placebo; 60-67% improved global status vs 14% placebo; 53-57% reduced dyspnea vs 12% placebo; p<0.001","methodology":"This was a two-part study. The efficacy trial enrolled 127 patients with severe heart failure (pulmonary wedge pressure ≥18 mmHg, cardiac index ≤2.7 L/min/m²) who received Swan-Ganz catheters and were randomized double-blind to placebo or one of two nesiritide doses for six hours. The comparative trial enrolled 305 patients randomized to open-label nesiritide or standard IV heart failure therapy for up to seven days without requiring hemodynamic monitoring.","limitations":"The efficacy trial was only six hours long, providing no long-term outcome data. The comparative trial was open-label, introducing potential bias. Neither trial assessed mortality as a primary endpoint. Subsequent larger trials (ASCEND-HF, 2011) would later show that nesiritide, while safe, did not reduce mortality or rehospitalization compared to placebo, tempering initial enthusiasm."},{"rthcId":"RPEP-00588","title":"Antimicrobial effects of alpha-MSH peptides.","authors":"Cutuli, M; Cristiani, S; Lipton, J M; Catania, A","year":2000,"journal":"Journal of leukocyte biology, 67(2), 233-9","doi":null,"pmid":"10670585","tags":["kpv","antimicrobial-peptides","immune-function","inflammation"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Alpha-MSH and KPV demonstrated broad-spectrum antimicrobial activity including against MRSA and drug-resistant organisms, with an anti-Candida mechanism resembling amphotericin B membrane disruption.","whyItMatters":"Drug-resistant infections kill over a million people annually. A tiny, easily synthesized peptide that kills MRSA and other resistant organisms could become a valuable addition to the antimicrobial arsenal.","specificNumbers":"","methodology":"In-vitro antimicrobial study testing alpha-MSH and KPV against expanded panels of gram-positive, gram-negative bacteria, and fungi using MIC/MBC determinations and mechanistic candidacidal assays.","limitations":"In-vitro activity. Concentrations required may exceed physiological levels. In-vivo efficacy not tested. The extremely small size of KPV could affect pharmacokinetics."},{"rthcId":"RPEP-00589","title":"Acyclic permutants of naturally occurring cyclic proteins. Characterization of cystine knot and beta-sheet formation in the macrocyclic polypeptide kalata B1.","authors":"Daly, N L; Craik, D J","year":2000,"journal":"The Journal of biological chemistry, 275(25), 19068-75","doi":null,"pmid":"10747913","tags":["cyclic-peptides","peptide-design"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Acyclic permutants of kalata B1 folded into native-like cystine knot structures without the circular backbone, but backbone cyclization was required for full biological activity and optimal structural stability.","whyItMatters":"For drug design, this means the cystine knot is a robust folding unit that could be used independently. But for maximum stability and activity, the full cyclic structure is needed.","specificNumbers":"","methodology":"In-vitro structural study using synthetic linear versions of kalata B1. NMR spectroscopy determined structures, thermal stability measured, and biological activity compared to native cyclotide.","limitations":"Study on a single cyclotide (kalata B1). Other cyclotides may behave differently. Specific activity assays were limited."},{"rthcId":"RPEP-00590","title":"A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9.","authors":"Donoghue, M; Hsieh, F; Baronas, E; Godbout, K; Gosselin, M; Stagliano, N; Donovan, M; Woolf, B; Robison, K; Jeyaseelan, R; Breitbart, R E; Acton, S","year":2000,"journal":"Circulation research, 87(5), E1-9","doi":null,"pmid":"10969042","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00591","title":"Thymosin alpha 1 in the treatment of cancer: from basic research to clinical application.","authors":"Garaci, E; Pica, F; Rasi, G; Favalli, C","year":2000,"journal":"International journal of immunopharmacology, 22(12), 1067-76","doi":null,"pmid":"11137613","tags":["thymosin-alpha-1","cancer","immune-function","clinical-trials"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Thymosin alpha-1 combined with low-dose IFN or IL-2 shows high efficacy against cancers in both preclinical models and human clinical trials, supporting its role as a cancer immunotherapy adjuvant.","whyItMatters":"Modern cancer immunotherapy is transforming oncology. Thymosin alpha-1 as an affordable, well-tolerated immune enhancer could complement expensive checkpoint inhibitors and expand immunotherapy access.","specificNumbers":"","methodology":"Review of basic research and clinical trial data on thymosin alpha-1 in cancer, covering combination with interferon, IL-2, and conventional cancer therapies.","limitations":"Brief review with limited detailed clinical data. The specific cancer types and trial designs were not comprehensively described. Larger trials needed for definitive evidence."},{"rthcId":"RPEP-00592","title":"Squash trypsin inhibitors from Momordica cochinchinensis exhibit an atypical macrocyclic structure.","authors":"Hernandez, J F; Gagnon, J; Chiche, L; Nguyen, T M; Andrieu, J P; Heitz, A; Trinh Hong, T; Pham, T T; Le Nguyen, D","year":2000,"journal":"Biochemistry, 39(19), 5722-30","doi":null,"pmid":"10801322","tags":["cyclic-peptides","peptide-design"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Three macrocyclic trypsin inhibitors (MCoTI-I, -II, -III) from Momordica cochinchinensis are the smallest known naturally cyclic peptides, with atypical backbone cyclization and potent trypsin inhibition.","whyItMatters":"Smaller cyclic peptides are easier to synthesize and more drug-like. These squash-derived miniature cyclotides expand the available toolkit for designing stable circular peptide drugs.","specificNumbers":"","methodology":"In-vitro study using gel filtration, ion exchange, and reverse-phase HPLC to isolate and sequence three cyclic peptides from squash seeds. Structure determined by proteolytic cleavage analysis.","limitations":"Structural characterization without biological activity beyond trypsin inhibition. The therapeutic potential needs to be explored through grafting experiments."},{"rthcId":"RPEP-00593","title":"Extensive neurite outgrowth and active synapse formation on self-assembling peptide scaffolds.","authors":"Holmes, T C; de Lacalle, S; Su, X; Liu, G; Rich, A; Zhang, S","year":2000,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 97(12), 6728-33","doi":null,"pmid":"10841570","tags":["peptide-design","neuroprotection"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Self-assembling peptide scaffolds supported extensive neurite outgrowth and formation of active, functional synapses, demonstrating programmable peptide-based materials for neural regeneration.","whyItMatters":"Nerve damage is often permanent because neurons struggle to regrow. A programmable scaffold that guides nerve growth and enables synapse formation could transform treatment of spinal cord injuries, brain damage, and neurodegenerative diseases.","specificNumbers":"","methodology":"In-vitro study using designed peptide scaffolds (ionic self-complementary peptides). Neural cell cultures assessed for neurite outgrowth and synapse formation using electrophysiology and fluorescent markers.","limitations":"In-vitro study. Translation to in-vivo nerve regeneration requires overcoming additional challenges including immune response, blood supply, and integration with existing neural circuits."},{"rthcId":"RPEP-00594","title":"The neuroimmunomodulatory peptide alpha-MSH.","authors":"Ichiyama, T; Sato, S; Okada, K; Catania, A; Lipton, J M","year":2000,"journal":"Annals of the New York Academy of Sciences, 917, 221-6","doi":null,"pmid":"11268347","tags":["kpv","inflammation","immune-function"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Alpha-MSH modulates inflammation through melanocortin receptor-mediated inhibition of NF-κB signaling, reducing pro-inflammatory cytokines, fever, and immune activation in both peripheral tissues and the central nervous system.","whyItMatters":"Alpha-MSH's ability to control inflammation through a natural pathway, rather than broadly suppressing immunity, offers a more targeted approach to treating inflammatory diseases with fewer side effects than conventional immunosuppressants.","specificNumbers":"","methodology":"Review of alpha-MSH immunomodulatory biology covering receptor distribution, signaling mechanisms (NF-κB inhibition), anti-inflammatory effects in multiple organ systems, and therapeutic implications.","limitations":"Review of predominantly preclinical data. Clinical translation of alpha-MSH-based therapies was still early. Some anti-inflammatory effects may require supraphysiological doses."},{"rthcId":"RPEP-00595","title":"Interleukin-2: structural and biological relatedness to opioid peptides.","authors":"Jiang, C L; Xu, D; Lu, C L; Wang, Y X; You, Z D; Liu, X Y","year":2000,"journal":"Neuroimmunomodulation, 8(1), 20-4","doi":null,"pmid":"10859484","tags":["opioid-peptides","immune-function","pain"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"IL-2 contains a structural domain resembling opioid peptides around its 45th Tyr residue that mediates analgesic effects, blocked by anti-opioid antibodies, revealing molecular overlap between immune and opioid signaling.","whyItMatters":"The discovery that an immune molecule contains an opioid-like pain-relieving domain provides molecular evidence for the long-suspected connection between immune activation and pain modulation.","specificNumbers":"","methodology":"In-vitro structural analysis of IL-2 identifying opioid-like domains, combined with functional pain assays showing IL-2 analgesia blocked by anti-endorphin, anti-leu-enkephalin, and anti-dynorphin antibodies.","limitations":"Structural similarity doesn't guarantee identical function. The physiological relevance of IL-2's analgesic domain at normal immune concentrations is unclear. In-vitro structure-function analysis."},{"rthcId":"RPEP-00596","title":"The effect on opioid peptides in the rat brain, after chronic treatment with the anabolic androgenic steroid, nandrolone decanoate.","authors":"Johansson, P; Hallberg, M; Kindlundh, A; Nyberg, F","year":2000,"journal":"Brain research bulletin, 51(5), 413-8","doi":null,"pmid":"10715562","tags":["opioid-peptides","neuropeptides","addiction"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Chronic nandrolone treatment altered met-enkephalin and dynorphin concentrations in limbic and striatal brain regions, providing a neurochemical mechanism for steroid-associated mood and behavioral disturbances.","whyItMatters":"Anabolic steroid abuse is widespread. Understanding the neurochemical basis of steroid-induced aggression and depression could help develop treatments and improve counseling for users.","specificNumbers":"","methodology":"Animal study. Rats received chronic nandrolone decanoate treatment. Regional brain opioid peptide concentrations (met-enkephalin, dynorphin) measured by radioimmunoassay in hypothalamus, striatum, periaqueductal gray, and other regions.","limitations":"Rat study. Steroid doses may differ from human abuse patterns. Behavioral consequences of peptide changes were not directly measured. Correlation between peptide levels and specific behaviors not established."},{"rthcId":"RPEP-00597","title":"Induction of a non-encephalitogenic type 2 T helper-cell autoimmune response in multiple sclerosis after administration of an altered peptide ligand in a placebo-controlled, randomized phase II trial. The Altered Peptide Ligand in Relapsing MS Study Group.","authors":"Kappos, L; Comi, G; Panitch, H; Oger, J; Antel, J; Conlon, P; Steinman, L","year":2000,"journal":"Nature medicine, 6(10), 1176-82","doi":null,"pmid":"11017151","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00598","title":"ARC POMC mRNA and PVN alpha-MSH are lower in obese relative to lean zucker rats.","authors":"Kim, E M; O'Hare, E; Grace, M K; Welch, C C; Billington, C J; Levine, A S","year":2000,"journal":"Brain research, 862(1-2), 11-6","doi":null,"pmid":"10799663","tags":["opioid-peptides","neuropeptides","weight-loss"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Obese Zucker rats had reduced arcuate POMC mRNA and PVN alpha-MSH levels compared to lean controls, indicating impaired melanocortin satiety signaling as a driver of genetic obesity.","whyItMatters":"Confirming that obesity involves deficient alpha-MSH satiety signaling supports melanocortin-based treatments. This pathway is now targeted by the obesity drug setmelanotide.","specificNumbers":"","methodology":"Animal study comparing mRNA expression (in situ hybridization) of POMC, PENK, PDYN, and NPY in arcuate nucleus and peptide immunoreactivity in PVN between obese and lean Zucker rats at 18 weeks.","limitations":"Zucker obesity is monogenic (leptin receptor mutation) and may not represent common human obesity. Peptide measurements at one timepoint don't capture dynamic regulation."},{"rthcId":"RPEP-00599","title":"Brain natriuretic peptide increases acutely and much more prominently than atrial natriuretic peptide during coronary angioplasty.","authors":"Kyriakides, Z S; Markianos, M; Michalis, L; Antoniadis, A; Nikolaou, N I; Kremastinos, D T","year":2000,"journal":"Clinical cardiology, 23(4), 285-8","doi":null,"pmid":"10763077","tags":["natriuretic-peptides","cardiovascular"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"BNP increased acutely and much more prominently than ANP during coronary angioplasty, with serial changes correlating with procedural myocardial stress, confirming BNP as the superior acute cardiac biomarker.","whyItMatters":"Monitoring heart stress during cardiac procedures helps identify complications early. BNP's rapid, proportionate response makes it the ideal real-time biomarker for this purpose.","specificNumbers":"","methodology":"Prospective cohort study with serial BNP and ANP measurements before, during, and after coronary angioplasty. Plasma levels correlated with procedural parameters.","limitations":"Single procedure type (angioplasty). Specific timing and magnitude of BNP rise may vary with different procedures. Sample size not specified in abstract."},{"rthcId":"RPEP-00600","title":"Coordinated Up-regulation by hypoxia of adrenomedullin and one of its putative receptors (RDC-1) in cells of the rat blood-brain barrier.","authors":"Ladoux, A; Frelin, C","year":2000,"journal":"The Journal of biological chemistry, 275(51), 39914-9","doi":null,"pmid":"10980200","tags":["neuropeptides","cardiovascular"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Hypoxia induced coordinated upregulation of adrenomedullin and its receptor RDC-1 in brain astrocytes and endothelial cells, with NF-κB-mediated transcriptional activation, suggesting an autocrine/paracrine protective mechanism at the blood-brain barrier.","whyItMatters":"Stroke and brain ischemia cause devastating damage. Understanding the brain's built-in protective responses, including ADM upregulation, could lead to therapies that enhance these natural defenses during stroke.","specificNumbers":"","methodology":"In-vitro study using cultured rat brain astrocytes and endothelial cells. Hypoxia exposure with measurement of ADM mRNA, protein, and RDC-1 receptor expression. Gene reporter assays identified NF-κB involvement.","limitations":"In-vitro study in isolated cells. The in-vivo relevance of this coordinated upregulation during actual stroke or ischemia needs confirmation."},{"rthcId":"RPEP-00601","title":"Repeated ethanol administration induces short- and long-term changes in enkephalin and dynorphin tissue concentrations in rat brain.","authors":"Lindholm, S; Ploj, K; Franck, J; Nylander, I","year":2000,"journal":"Alcohol (Fayetteville, N.Y.), 22(3), 165-71","doi":null,"pmid":"11163124","tags":["opioid-peptides","addiction"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Repeated ethanol produced both short-term (24h) and persistent (2-week) alterations in enkephalin and dynorphin tissue concentrations in mesolimbic reward regions, providing a neurochemical basis for alcohol craving and relapse.","whyItMatters":"Understanding why alcoholics relapse weeks after their last drink is crucial for treatment. Long-lasting opioid system changes in reward circuits provide a biological explanation and therapeutic target.","specificNumbers":"","methodology":"Animal study in rats. Repeated ethanol administration followed by measurement of opioid peptide concentrations at 24 hours and 2 weeks post-treatment in nucleus accumbens, striatum, and other mesolimbic regions.","limitations":"Rat model. Ethanol dosing patterns may not match human drinking. Two weeks may not reflect longer-term persistence. Peptide concentration changes don't directly prove functional consequences."},{"rthcId":"RPEP-00602","title":"Plasma cardiac natriuretic peptides as biochemical markers of recurrence of atrial fibrillation in patients with mild congestive heart failure.","authors":"Mabuchi, N; Tsutamoto, T; Maeda, K; Kinoshita, M","year":2000,"journal":"Japanese circulation journal, 64(10), 765-71","doi":null,"pmid":"11059617","tags":["natriuretic-peptides","cardiovascular"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Elevated pre-cardioversion BNP and ANP predicted atrial fibrillation recurrence after DC cardioversion in mild CHF patients, and BNP declined after successful rhythm restoration.","whyItMatters":"Knowing which AF patients will maintain normal rhythm after cardioversion avoids futile procedures and guides treatment planning. Simple blood tests predicting success would improve clinical decision-making.","specificNumbers":"","methodology":"Prospective cohort study measuring plasma ANP and BNP before and after DC cardioversion in patients with mild congestive heart failure and atrial fibrillation. AF recurrence tracked during follow-up.","limitations":"Small cohort of patients with mild CHF only. Specific cutoff values and predictive accuracy not detailed. Other factors also predict AF recurrence."},{"rthcId":"RPEP-00603","title":"A simple test for growth hormone deficiency in adults.","authors":"Mahajan, T; Lightman, S L","year":2000,"journal":"The Journal of clinical endocrinology and metabolism, 85(4), 1473-6","doi":null,"pmid":"10770184","tags":["ghrp","hormone-optimization","clinical-trials"],"studyType":"clinical-trial","evidenceStrength":"strong","keyFinding":"The combined GHRP-6 + GHRH stimulation test accurately diagnosed adult GH deficiency with high sensitivity and specificity, requiring a single blood draw at 15-30 minutes and avoiding the risks of insulin-induced hypoglycemia.","whyItMatters":"A safer, simpler test for adult GH deficiency could enable wider screening and earlier treatment, avoiding the risks of deliberate hypoglycemia in the insulin tolerance test.","specificNumbers":"","methodology":"Clinical trial comparing the GHRP-6 + GHRH combined test to the insulin tolerance test in adults with confirmed GH deficiency and healthy controls. GH peak values and diagnostic accuracy assessed.","limitations":"Study in a selected population of confirmed GH-deficient and healthy adults. Cutoff values may need validation in larger populations. The test requires GHRP-6 availability."},{"rthcId":"RPEP-00604","title":"Clinical correlates of elevated plasma natriuretic peptides and Big endothelin-1 in a population of ambulatory patients with heart failure. A substudy of the Italian Network on Congestive Heart Failure (IN-CHF) registry. IN-CHF Investigators.","authors":"Masson, S; Gorini, M; Salio, M; Lucci, D; Latini, R; Maggioni, A P","year":2000,"journal":"Italian heart journal : official journal of the Italian Federation of Cardiology, 1(4), 282-8","doi":null,"pmid":"10824729","tags":["natriuretic-peptides","cardiovascular"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"BNP, ANP, and Big Endothelin-1 each independently correlated with heart failure severity but reflected different pathophysiological aspects — cardiac volume overload versus vascular/renal dysfunction — providing complementary clinical information.","whyItMatters":"Heart failure is a complex syndrome with multiple contributing mechanisms. Using multiple peptide biomarkers provides a more complete picture of each patient's specific pathophysiology, enabling more personalized treatment.","specificNumbers":"","methodology":"Cross-sectional cohort study in ambulatory heart failure patients. Plasma BNP, ANP, and Big Endothelin-1 correlated with clinical parameters including NYHA class, echocardiographic measurements, and renal function.","limitations":"Cross-sectional design cannot establish causation. Ambulatory patients may not represent the full heart failure spectrum. Specific cutoff values not established."},{"rthcId":"RPEP-00605","title":"Adrenomedullin: a new peptidergic regulator of the vascular function.","authors":"Minamino, N; Kangawa, K; Matsuo, H","year":2000,"journal":"Clinical hemorheology and microcirculation, 23(2-4), 95-102","doi":null,"pmid":"11321465","tags":["neuropeptides","cardiovascular"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Adrenomedullin dilates blood vessels through dual mechanisms — direct smooth muscle relaxation and endothelial NO release — with autocrine/paracrine production by vascular endothelial and smooth muscle cells.","whyItMatters":"Understanding AM's dual vasodilatory mechanism explains its exceptional potency and suggests it could be therapeutically valuable for conditions requiring blood vessel relaxation.","specificNumbers":"","methodology":"Review of adrenomedullin vascular biology covering production, receptor expression, signaling mechanisms, and roles in cardiovascular diseases.","limitations":"Brief review with limited clinical data. The relative importance of each vasodilatory mechanism may vary between vascular beds."},{"rthcId":"RPEP-00606","title":"Melatonin is responsible for the nocturnal increase observed in serum and thymus of thymosin alpha1 and thymulin concentrations: observations in rats and humans.","authors":"Molinero, P; Soutto, M; Benot, S; Hmadcha, A; Guerrero, J M","year":2000,"journal":"Journal of neuroimmunology, 103(2), 180-8","doi":null,"pmid":"10696913","tags":["thymosin-alpha-1","immune-function","sleep"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Melatonin directly regulates thymosin alpha-1 and thymulin production, driving their nocturnal peaks in serum and thymus. Pinealectomy abolished and melatonin replacement restored the circadian thymic peptide pattern.","whyItMatters":"This links sleep directly to immune function at the molecular level. When you sleep, melatonin rises, which boosts thymic peptides that regulate immunity. Sleep deprivation disrupts this cycle, potentially impairing immune function.","specificNumbers":"","methodology":"Animal study in rats measuring thymosin alpha-1 and thymulin concentrations in serum and thymus at multiple timepoints. Pinealectomy and melatonin replacement experiments. Prothymosin alpha gene expression assessed.","limitations":"Rat study. Circadian patterns may differ in humans. The functional immune consequences of melatonin-driven thymic peptide peaks were not directly measured."},{"rthcId":"RPEP-00607","title":"Plasma neuropeptide-Y concentrations in humans exposed to military survival training.","authors":"Morgan, C A; Wang, S; Southwick, S M; Rasmusson, A; Hazlett, G; Hauger, R L; Charney, D S","year":2000,"journal":"Biological psychiatry, 47(10), 902-9","doi":null,"pmid":"10807963","tags":["neuropeptides","anxiety-mood"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Special forces soldiers showed higher plasma NPY during extreme stress and faster post-stress recovery compared to regular troops, with higher NPY correlating with better performance and less psychological distress.","whyItMatters":"Understanding biological resilience has implications for treating PTSD, selecting personnel for high-stress occupations, and developing interventions to boost stress resistance.","specificNumbers":"","methodology":"Prospective cohort study in military personnel during survival, evasion, resistance, and escape (SERE) training. Plasma NPY measured before, during, and after extreme stress exposure. Special forces compared to regular troops.","limitations":"Observational study; can't determine if high NPY causes resilience or if resilient individuals happen to produce more NPY. Special forces selection bias. Specific training context may not generalize."},{"rthcId":"RPEP-00608","title":"Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone.","authors":"Ng, F M; Sun, J; Sharma, L; Libinaka, R; Jiang, W J; Gianello, R","year":2000,"journal":"Hormone research, 53(6), 274-8","doi":null,"pmid":"11146367","tags":["growth-hormone","weight-loss"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Oral AOD9604 — a synthetic peptide fragment based on the fat-burning region of human growth hormone — reduced weight gain by over 50% in obese Zucker rats. Treated animals gained only 15.8 g versus 35.6 g in controls over 19 days of daily oral dosing at 500 µg/kg body weight. Fat tissue from treated animals showed increased lipolytic (fat-breaking) activity.\n\nCritically, unlike full-length growth hormone (which is known to worsen insulin resistance with chronic use), AOD9604 showed no adverse effects on insulin sensitivity when tested with euglycemic clamp techniques — considered the gold standard for measuring insulin action. This separation of fat-burning benefits from growth hormone's diabetogenic side effects was the key finding.","whyItMatters":"Growth hormone has powerful fat-burning effects, but chronic use causes insulin resistance and other serious side effects. AOD9604 represents an attempt to isolate just the fat-burning portion of growth hormone in a smaller, safer peptide. The fact that it worked orally (most peptides are destroyed by digestion) and didn't impair insulin sensitivity made it an attractive candidate for obesity treatment. This early study launched AOD9604 into clinical development and established the rationale behind the peptide's continued popularity in compounding pharmacies.","specificNumbers":"","methodology":"Obese Zucker rats (a standard model for metabolic obesity) received daily oral doses of AOD9604 at 500 µg/kg body weight for 19 days. Researchers measured body weight gain, fat tissue lipolytic activity, blood glucose, and insulin levels. Insulin sensitivity was assessed using euglycemic clamp techniques, comparing AOD9604-treated animals to both untreated controls and animals treated with intact human growth hormone.","limitations":"This is a rat study from 2000 — the obese Zucker rat model, while useful, does not fully replicate human obesity. The study was short (19 days) and measured weight gain reduction rather than established fat loss. Sample sizes typical of early preclinical work. Subsequent human clinical trials of AOD9604 failed to show significant weight loss, despite these promising animal results."},{"rthcId":"RPEP-00609","title":"Differential mechanisms mediating descending pain controls for antinociception induced by supraspinally administered endomorphin-1 and endomorphin-2 in the mouse.","authors":"Ohsawa, M; Mizoguchi, H; Narita, M; Chu, M; Nagase, H; Tseng, L F","year":2000,"journal":"The Journal of pharmacology and experimental therapeutics, 294(3), 1106-11","doi":null,"pmid":"10945866","tags":["opioid-peptides","pain","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Endomorphin-2 produces analgesia through both direct mu-opioid receptor activation and indirect dynorphin A release activating kappa receptors via descending pain pathways, while endomorphin-1 uses only the mu pathway.","whyItMatters":"Understanding that different endogenous opioid peptides engage different pain pathways helps design more targeted analgesics and explains why the body uses multiple opioid peptides.","specificNumbers":"","methodology":"Animal study using supraspinal administration of endomorphins with selective receptor antagonists and anti-peptide antibodies to dissect the descending pain control pathways involved.","limitations":"Animal study with supraspinal peptide injection. The relative importance of each pathway for different pain conditions is unknown. Pharmacological dissection uses selective but not perfectly specific tools."},{"rthcId":"RPEP-00610","title":"Brain natriuretic peptide is a predictor of anthracycline-induced cardiotoxicity.","authors":"Okumura, H; Iuchi, K; Yoshida, T; Nakamura, S; Takeshima, M; Takamatsu, H; Ikeno, A; Usuda, K; Ishikawa, T; Ohtake, S; Matsuda, T","year":2000,"journal":"Acta haematologica, 104(4), 158-63","doi":null,"pmid":"11279304","tags":["natriuretic-peptides","cancer","cardiovascular"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Persistent BNP elevation after anthracycline chemotherapy predicted development of cardiotoxicity, distinguishing at-risk patients from those with only transient, benign BNP rises.","whyItMatters":"Anthracyclines are among the most effective cancer drugs, but heart damage limits their use. A blood test that predicts who will develop heart damage enables personalized dosing — maximizing cancer treatment while protecting the heart.","specificNumbers":"","methodology":"Prospective cohort study measuring serial plasma BNP before, during, and after anthracycline chemotherapy. BNP trajectories correlated with echocardiographic cardiac function and clinical cardiotoxicity endpoints.","limitations":"Specific patient numbers and BNP cutoff values not detailed in abstract. Results may vary with different anthracycline regimens. Other biomarkers (troponin) also have predictive value."},{"rthcId":"RPEP-00611","title":"Growth hormone secretagogue binding sites in peripheral human tissues.","authors":"Papotti, M; Ghè, C; Cassoni, P; Catapano, F; Deghenghi, R; Ghigo, E; Muccioli, G","year":2000,"journal":"The Journal of clinical endocrinology and metabolism, 85(10), 3803-7","doi":null,"pmid":"11061542","tags":["ghrp","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Specific GHS binding sites identified in human adrenal, gonadal (ovary/testis), cardiac, and vascular tissues, with ghrelin confirmed as an endogenous ligand at these sites.","whyItMatters":"Each new tissue where GHS receptors are found suggests new biological functions and potential therapeutic applications — or safety concerns — for GH secretagogue use.","specificNumbers":"","methodology":"In-vitro binding study using 125I-Tyr-Ala-hexarelin on membrane preparations from multiple human tissue types. Ghrelin competition binding confirmed endogenous ligand activity.","limitations":"In-vitro binding doesn't prove functional activity. Tissue availability limited to surgical specimens. The physiological role of GHS-R in each tissue remains to be determined."},{"rthcId":"RPEP-00612","title":"CCK peptides with combined features of hexa- and tetrapeptide CCK-A agonists.","authors":"Pierson, M E; Comstock, J M; Simmons, R D; Julien, R; Kaiser, F; Rosamond, J D","year":2000,"journal":"Journal of medicinal chemistry, 43(12), 2350-5","doi":null,"pmid":"10882360","tags":["neuropeptides","weight-loss","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Hybrid CCK-A agonist peptides combining structural features of hexapeptide and tetrapeptide classes showed potent receptor binding and selectivity, advancing design of satiety-inducing peptide drugs for obesity.","whyItMatters":"Obesity is a global health crisis. CCK-based drugs that trigger natural satiety could help people eat less without the side effects of stimulant-based appetite suppressants.","specificNumbers":"","methodology":"In-vitro study designing and testing new CCK peptide analogs for CCK-A receptor binding affinity, selectivity over CCK-B, and functional activity.","limitations":"In-vitro binding and selectivity data only. In-vivo satiety effects not demonstrated for the new hybrids. Peptide stability and oral bioavailability are ongoing challenges."},{"rthcId":"RPEP-00613","title":"Basal levels and alcohol-induced changes in nociceptin/orphanin FQ, dynorphin, and enkephalin levels in C57BL/6J mice.","authors":"Ploj, K; Roman, E; Gustavsson, L; Nylander, I","year":2000,"journal":"Brain research bulletin, 53(2), 219-26","doi":null,"pmid":"11044599","tags":["opioid-peptides","addiction","neuropeptides"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Alcohol-preferring mice had lower baseline nociceptin and dynorphin B in reward regions, with alcohol consumption producing additional changes in met-enkephalin levels, linking opioid/nociceptin system configuration to alcohol preference.","whyItMatters":"Identifying pre-existing opioid system differences in alcohol-preferring animals suggests genetic opioid vulnerability to alcoholism, which could enable identification and early intervention in at-risk humans.","specificNumbers":"","methodology":"Animal study comparing basal opioid peptide levels (nociceptin, dynorphin B, met-enkephalin) in alcohol-preferring C57BL/6J mice vs alcohol-avoiding DBA/2J mice, and measuring changes after voluntary alcohol consumption.","limitations":"Mouse strain comparison; results may not directly translate to human genetics. Voluntary drinking model may not fully represent human alcoholism. Multiple brain regions measured increase type I error risk."},{"rthcId":"RPEP-00614","title":"Sweet Tooth, a novel receptor protein-tyrosine kinase with C-type lectin-like extracellular domains.","authors":"Reidling, J C; Miller, M A; Steele, R E","year":2000,"journal":"The Journal of biological chemistry, 275(14), 10323-30","doi":null,"pmid":"10744720","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00615","title":"Gamma-hydroxybutyric acid and growth hormone secretion studies in rats and dogs.","authors":"Rigamonti, A E; Müller, E E","year":2000,"journal":"Alcohol (Fayetteville, N.Y.), 20(3), 293-304","doi":null,"pmid":"10869872","tags":["ghrp","hormone-optimization","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"GHB stimulated GH release partly through GH secretagogue receptor-related pathways in addition to GABA mechanisms, with additive effects when combined with GHRP in both rats and dogs.","whyItMatters":"Understanding how GHB releases GH has implications for both sports doping (GHB used for GH enhancement) and for understanding the GH regulatory network's complexity.","specificNumbers":"","methodology":"Animal study in rats and dogs comparing GHB's GH-releasing effects alone and in combination with GHRP. Pharmacological blocking experiments to dissect GABA versus GH secretagogue pathway contributions.","limitations":"Animal study. GHB doses used may differ from recreational or clinical use. The exact point of pathway convergence was not identified. GHB is a controlled substance with abuse potential."},{"rthcId":"RPEP-00616","title":"Central changes in nociceptin dynorphin B and Met-enkephalin-Arg-Phe in different models of nociception.","authors":"Rosén, A; Lundeberg, T; Bytner, B; Nylander, I","year":2000,"journal":"Brain research, 857(1-2), 212-8","doi":null,"pmid":"10700570","tags":["opioid-peptides","neuropeptides","pain"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Neuropathic and inflammatory chronic pain models produced distinct regional patterns of nociceptin, dynorphin B, and met-enkephalin changes in brain pain pathways, indicating pain type-specific opioid system plasticity.","whyItMatters":"Not all chronic pain is the same. Understanding that different pain types produce different opioid system changes explains why treatments effective for one pain type may fail for another.","specificNumbers":"","methodology":"Animal study comparing two chronic pain models (neuropathic: sciatic nerve injury; inflammatory: adjuvant-induced) in rats. Regional brain opioid peptide concentrations measured by RIA in periaqueductal gray, thalamus, and other pain-processing areas.","limitations":"Rat models may not fully represent human chronic pain. Peptide measurements at a single timepoint may miss dynamic changes. Statistical corrections for multiple comparisons not detailed."},{"rthcId":"RPEP-00617","title":"Oral estradiol administration modulates continuous intravenous growth hormone (GH)-releasing peptide-2-driven GH secretion in postmenopausal women.","authors":"Shah, N; Evans, W S; Bowers, C Y; Veldhuis, J D","year":2000,"journal":"The Journal of clinical endocrinology and metabolism, 85(8), 2649-59","doi":null,"pmid":"10946861","tags":["ghrp","hormone-optimization","clinical-trials","fertility"],"studyType":"RCT","evidenceStrength":"strong","keyFinding":"Oral estradiol supplementation in postmenopausal women modulated continuous GHRP-2-driven GH secretion, increasing IGF-1 response but altering GH pulse dynamics, revealing estrogen-GH secretagogue interactions important for clinical dosing.","whyItMatters":"Millions of postmenopausal women use estrogen therapy and may also benefit from GH secretagogues. Understanding how these interact is essential for safe, effective combination therapy.","specificNumbers":"","methodology":"Randomized study in 10 healthy postmenopausal women. Oral estradiol supplementation followed by 24-hour continuous GHRP-2 infusion with 10-minute blood sampling. GH deconvolution analysis and IGF-1 measurement.","limitations":"Small study (10 women). Oral estradiol (which undergoes first-pass liver metabolism) may differ from transdermal estradiol in GH axis effects. Acute estrogen effects may not reflect chronic use."},{"rthcId":"RPEP-00618","title":"Effects of milk-derived bioactives: an overview.","authors":"Shah, N P","year":2000,"journal":"The British journal of nutrition, 84 Suppl 1, S3-10","doi":null,"pmid":"11242440","tags":["bioactive-food-peptides","opioid-peptides","cardiovascular"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Milk-derived peptides from casein and whey digestion include opioid peptides (casomorphins), antihypertensive peptides (casokinins), mineral carriers (casein phosphopeptides), and other bioactives with diverse health effects.","whyItMatters":"Understanding milk's bioactive peptides explains health benefits beyond calories and calcium, supporting functional food development and targeted dairy product design.","specificNumbers":"","methodology":"Review of published research on bioactive peptides released from milk protein digestion, covering multiple peptide families and their demonstrated biological activities.","limitations":"Brief review. The bioavailability and physiological significance of milk-derived peptides at normal consumption levels is debated."},{"rthcId":"RPEP-00619","title":"Changes in thymosin-alpha(1)content in patients with nonspecific gynecologic diseases depending on inflammation type and efficacy of antiinflammatory and immunomodulating therapy.","authors":"Shurlygina, A; Litvinenko, G; Dergacheva, T; Trufakin, V","year":2000,"journal":"Bulletin of experimental biology and medicine, 130(9), 895-7","doi":null,"pmid":"11177275","tags":["thymosin-alpha-1","immune-function","inflammation"],"studyType":"cohort","evidenceStrength":"preliminary","keyFinding":"Thymosin alpha-1 plasma levels and circadian rhythms were altered in gynecologic inflammation, varying by inflammation type and normalizing with successful treatment.","whyItMatters":"Thymosin alpha-1 as a treatment response biomarker could help clinicians monitor whether gynecologic inflammation therapy is working without invasive procedures.","specificNumbers":"","methodology":"Cohort study measuring plasma thymosin alpha-1 concentrations at multiple timepoints in women with inflammatory gynecologic diseases compared to healthy controls.","limitations":"Small study with limited abstract details. Specific inflammation types and sample sizes not described. Circadian sampling adds complexity."},{"rthcId":"RPEP-00620","title":"Gastric mucosal lesions induced by complete dopamine system failure in rats. The effects of dopamine agents, ranitidine, atropine, omeprazole and pentadecapeptide BPC 157.","authors":"Sikiric, P; Separovic, J; Buljat, G; Anic, T; Stancic-Rokotov, D; Mikus, D; Duplancic, B; Marovic, A; Zoricic, I; Prkacin, I; Lovric-Bencic, M; Aralica, G; Ziger, T; Perovic, D; Jelovac, N; Dodig, G; Rotkvic, I; Mise, S; Seiwerth, S; Turkovic, B; Grabarevic, Z; Petek, M; Rucman, R","year":2000,"journal":"Journal of physiology, Paris, 94(2), 105-10","doi":null,"pmid":"10791690","tags":["bpc-157","gut-healing","neuroprotection"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Complete dopamine system failure (combined haloperidol + reserpine) produced severe gastric lesions. BPC-157 provided superior healing compared to ranitidine, atropine, and other agents while also reducing associated catalepsy.","whyItMatters":"This demonstrates that dopamine is essential for stomach health and that BPC-157 can heal damage even from the most extreme dopaminergic disruption, reinforcing its unique interaction with the dopamine system.","specificNumbers":"","methodology":"Animal study in rats. Complete dopamine system failure induced by combined haloperidol + reserpine. BPC-157 compared to multiple reference drugs for gastric lesion healing and behavioral (catalepsy) effects.","limitations":"Extreme pharmacological model that may not represent clinical scenarios. The mechanism of BPC-157's dopamine interaction was not fully elucidated."},{"rthcId":"RPEP-00621","title":"The antidepressant effect of an antiulcer pentadecapeptide BPC 157 in Porsolt's test and chronic unpredictable stress in rats. A comparison with antidepressants.","authors":"Sikiric, P; Separovic, J; Buljat, G; Anic, T; Stancic-Rokotov, D; Mikus, D; Marovic, A; Prkacin, I; Duplancic, B; Zoricic, I; Aralica, G; Lovric-Bencic, M; Ziger, T; Perovic, D; Rotkvic, I; Mise, S; Hanzevacki, M; Hahn, V; Seiwerth, S; Turkovic, B; Grabarevic, Z; Petek, M; Rucman, R","year":2000,"journal":"Journal of physiology, Paris, 94(2), 99-104","doi":null,"pmid":"10791689","tags":["bpc-157","anxiety-mood"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"BPC-157 showed antidepressant activity in both the Porsolt forced swim test (reduced immobility) and chronic unpredictable stress model in rats, with effects comparable to established antidepressants.","whyItMatters":"Depression affects over 300 million people globally, and current antidepressants have significant side effects and slow onset. A peptide with antidepressant properties and BPC-157's known safety profile could offer a new treatment approach.","specificNumbers":"","methodology":"Animal study in rats using two validated depression models: Porsolt's forced swim test (behavioral despair) and chronic unpredictable stress (anhedonia model). BPC-157 compared to standard antidepressant drugs.","limitations":"Rat depression models are approximations of human depression. Behavioral endpoints don't confirm subjective mood improvement. The mechanism of antidepressant action was not determined."},{"rthcId":"RPEP-00622","title":"Adenosine: A partial agonist of the growth hormone secretagogue receptor.","authors":"Smith, R G; Griffin, P R; Xu, Y; Smith, A G; Liu, K; Calacay, J; Feighner, S D; Pong, C; Leong, D; Pomés, A; Cheng, K; Van der Ploeg, L H; Howard, A D; Schaeffer, J; Leonard, R J","year":2000,"journal":"Biochemical and biophysical research communications, 276(3), 1306-13","doi":null,"pmid":"11027627","tags":["ghrp","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Adenosine was identified as a partial agonist of the GH secretagogue receptor (GHS-R) from hypothalamic extract fractionation, producing submaximal receptor activation compared to full agonists like ghrelin.","whyItMatters":"Adenosine is everywhere in the body and influences sleep, inflammation, and energy metabolism. Its interaction with the GH secretagogue receptor creates a new link between cellular energy status and growth hormone regulation.","specificNumbers":"","methodology":"In-vitro study fractionating porcine hypothalamic extracts and testing fractions on HEK293 cells expressing GHS-R. Adenosine identified by chromatography and confirmed with receptor binding and functional assays.","limitations":"In-vitro finding. Whether adenosine activates GHS-R at physiological concentrations in the brain is uncertain. Partial agonism may not produce significant GH release in vivo."},{"rthcId":"RPEP-00623","title":"The effect of delta sleep-inducing peptide on the EEG and power spectra in rat.","authors":"Stanojlović, O P; Zivanović, D P; Susić, V T","year":2000,"journal":"Indian journal of physiology and pharmacology, 44(4), 428-34","doi":null,"pmid":"11214497","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00624","title":"Serum atrial natriuretic peptide concentration is a useful predictor of atrial standstill in patients with heart failure.","authors":"Suguta, M; Hara, K; Nakano, A; Amano, A; Hasegawa, A; Kurabayashi, M","year":2000,"journal":"Japanese circulation journal, 64(7), 537-40","doi":null,"pmid":"10929785","tags":["natriuretic-peptides","cardiovascular"],"studyType":"case-report","evidenceStrength":"preliminary","keyFinding":"Atrial standstill produced a distinctive natriuretic peptide pattern: normal-to-low ANP (from non-functional atria) with markedly elevated BNP (from stressed ventricles), providing a potential diagnostic biomarker signature.","whyItMatters":"Atrial standstill can be missed on routine ECG. A distinctive blood biomarker pattern (high BNP with paradoxically low ANP) could flag this rare but dangerous condition.","specificNumbers":"","methodology":"Case report of two patients with atrial standstill (one cardiac amyloidosis, one dilated cardiomyopathy). Plasma ANP and BNP measured alongside echocardiographic findings.","limitations":"Only 2 cases — observational, not diagnostic validation. The ANP-BNP dissociation pattern needs confirmation in larger series."},{"rthcId":"RPEP-00625","title":"Involvement of dynorphin in immobilization stress-induced antinociception in the mouse.","authors":"Suh, H W; Song, D K; Huh, S O; Kim, Y H","year":2000,"journal":"European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 10(5), 407-13","doi":null,"pmid":"10974614","tags":["opioid-peptides","pain","anxiety-mood"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"ICV and intrathecal anti-dynorphin antibodies blocked immobilization stress-induced analgesia, while anti-enkephalin and anti-endorphin antibodies did not, establishing dynorphin as the specific mediator at both brain and spinal levels.","whyItMatters":"Understanding that stress analgesia uses dynorphin specifically (not endorphins) provides a molecular target for managing stress-related pain conditions and understanding how the body copes with extreme stress.","specificNumbers":"","methodology":"Animal study in mice. Anti-opioid peptide antibodies (dynorphin, met-enkephalin, leu-enkephalin, beta-endorphin) administered ICV or intrathecally before immobilization stress. Pain response assessed by tail-flick and paw-pressure tests.","limitations":"Mouse study with restraint stress model. Specific aspects of the stressor may determine which opioid system is engaged. Acute stress model may not reflect chronic stress situations."},{"rthcId":"RPEP-00626","title":"From opiate pharmacology to opioid peptide physiology.","authors":"Terenius, L","year":2000,"journal":"Upsala journal of medical sciences, 105(1), 1-15","doi":null,"pmid":"10893049","tags":["opioid-peptides","pain","receptor-signaling"],"studyType":"review","evidenceStrength":"strong","keyFinding":"The pharmacological uniqueness of opiates implied endogenous opioid ligands must exist, leading to the discovery of enkephalins, beta-endorphin, and dynorphins — a family of peptides with diverse roles in pain, mood, and behavior.","whyItMatters":"The discovery of endogenous opioid peptides is one of neuroscience's most important breakthroughs. It transformed understanding of pain, addiction, mood, and immune function, and continues to drive drug development.","specificNumbers":"","methodology":"Historical review by a pioneer in the field, tracing the scientific journey from opiate pharmacology to endogenous opioid peptide discovery.","limitations":"Historical perspective focused on one researcher's experience. May not cover all contributions to the field."},{"rthcId":"RPEP-00627","title":"Treatment of heart failure guided by plasma aminoterminal brain natriuretic peptide (N-BNP) concentrations.","authors":"Troughton, R W; Frampton, C M; Yandle, T G; Espiner, E A; Nicholls, M G; Richards, A M","year":2000,"journal":"Lancet (London, England), 355(9210), 1126-30","doi":null,"pmid":"10791374","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00628","title":"Angiotensin II type 1 receptor antagonist decreases plasma levels of tumor necrosis factor alpha, interleukin-6 and soluble adhesion molecules in patients with chronic heart failure.","authors":"Tsutamoto, T; Wada, A; Maeda, K; Mabuchi, N; Hayashi, M; Tsutsui, T; Ohnishi, M; Sawaki, M; Fujii, M; Matsumoto, T; Kinoshita, M","year":2000,"journal":"Journal of the American College of Cardiology, 35(3), 714-21","doi":null,"pmid":"10716475","tags":["natriuretic-peptides","cardiovascular","inflammation"],"studyType":"RCT","evidenceStrength":"moderate","keyFinding":"Valsartan (angiotensin II type 1 receptor blocker) reduced TNF-α, IL-6, soluble ICAM-1, and BNP in heart failure patients, demonstrating anti-inflammatory effects of angiotensin blockade beyond hemodynamic improvements.","whyItMatters":"Inflammation drives heart failure progression. Showing that angiotensin blockers reduce inflammatory markers provides a mechanistic explanation for their life-saving benefits beyond blood pressure lowering.","specificNumbers":"","methodology":"Randomized controlled trial in patients with congestive heart failure. Valsartan versus standard therapy. TNF-α, IL-6, soluble ICAM-1, and BNP measured before and after treatment.","limitations":"Open-label design in the abstract description. Specific sample size and treatment duration not detailed. The relative contribution of anti-inflammatory versus hemodynamic effects to clinical outcomes is unclear."},{"rthcId":"RPEP-00629","title":"Adenosine is an agonist of the growth hormone secretagogue receptor.","authors":"Tullin, S; Hansen, B S; Ankersen, M; Møller, J; Von Cappelen, K A; Thim, L","year":2000,"journal":"Endocrinology, 141(9), 3397-402","doi":null,"pmid":"10965912","tags":["ghrp","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Adenosine and multiple analogs demonstrated agonist activity at the GH secretagogue receptor (GHS-R), establishing a novel link between cellular energy metabolism and growth hormone regulation.","whyItMatters":"This connects energy metabolism to GH regulation at the molecular level. Exercise, fasting, and other energy-demanding states increase adenosine, which could then boost GH through the ghrelin receptor.","specificNumbers":"","methodology":"In-vitro study identifying adenosine as a GHS-R agonist from hypothalamic extracts. Confirmed with multiple adenosine analogs, receptor binding assays, and functional calcium flux measurements in GHS-R expressing cells.","limitations":"In-vitro findings. Whether physiological adenosine concentrations in the brain achieve sufficient GHS-R activation is unconfirmed. Other adenosine receptors exist and may complicate the picture in vivo."},{"rthcId":"RPEP-00630","title":"A paradoxical gender dissociation within the growth hormone/insulin-like growth factor I axis during protracted critical illness.","authors":"Van den Berghe, G; Baxter, R C; Weekers, F; Wouters, P; Bowers, C Y; Veldhuis, J D","year":2000,"journal":"The Journal of clinical endocrinology and metabolism, 85(1), 183-92","doi":null,"pmid":"10634385","tags":["ghrp","hormone-optimization","clinical-trials"],"studyType":"clinical-trial","evidenceStrength":"strong","keyFinding":"Female ICU patients maintained higher GH pulse frequency and IGF-1 levels than males during protracted critical illness, with gender-modulated responses to GHRP-2/GHRH stimulation, potentially explaining women's better ICU survival.","whyItMatters":"Understanding why women survive ICU better could lead to gender-tailored treatment strategies, including sex-specific GH secretagogue dosing protocols.","specificNumbers":"","methodology":"Clinical trial with intensive GH profiling (10-min sampling over 24h) in prolonged critically ill men and women, with GHRP-2/GHRH stimulation testing. IGF-1 and binding proteins measured.","limitations":"Small sample inherent to intensive ICU sampling. Gender comparison confounded by baseline sex differences in GH secretion. Mechanistic link to survival not directly established."},{"rthcId":"RPEP-00631","title":"Opioid peptide gene expression primes cardiogenesis in embryonal pluripotent stem cells.","authors":"Ventura, C; Maioli, M","year":2000,"journal":"Circulation research, 87(3), 189-94","doi":null,"pmid":"10926868","tags":["opioid-peptides","cardiovascular","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Opioid peptide gene expression (prodynorphin, proenkephalin) preceded cardiac transcription factor activation (GATA-4, Nkx-2.5) during cardiogenesis in embryonic stem cells, suggesting opioid peptides prime heart cell development.","whyItMatters":"Understanding what signals drive heart cell development could improve cardiac regenerative medicine. The opioid system's involvement adds an entirely new dimension to cardiac development biology.","specificNumbers":"","methodology":"In-vitro study using embryonal pluripotent stem cells differentiating into cardiomyocytes. Gene expression timeline for opioid peptides and cardiac transcription factors measured during DMSO-induced differentiation.","limitations":"In-vitro stem cell model using DMSO differentiation. Gene expression timing doesn't prove causation. Human cardiac development may differ from cell culture models."},{"rthcId":"RPEP-00632","title":"Pretreatment with growth hormone-releasing peptide-2 directly protects against the diastolic dysfunction of myocardial stunning in an isolated, blood-perfused rabbit heart model.","authors":"Weekers, F; Van Herck, E; Isgaard, J; Van den Berghe, G","year":2000,"journal":"Endocrinology, 141(11), 3993-9","doi":null,"pmid":"11089529","tags":["ghrp","cardiovascular"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"GHRP-2 pretreatment directly protected against diastolic myocardial stunning in isolated hearts, while recombinant GH did not, demonstrating GH-independent, direct cardiac protection through cardiac GH secretagogue receptors.","whyItMatters":"Direct cardiac protection by GHRP-2 — independent of GH — means it could be used during cardiac surgery or heart attacks to prevent stunning damage without the risks of GH therapy.","specificNumbers":"","methodology":"Animal study using isolated, blood-perfused rabbit hearts. GHRP-2 or rhGH administered before ischemia-reperfusion protocol. Diastolic and systolic function measured by pressure-volume analysis.","limitations":"Isolated heart model lacks normal circulatory and hormonal context. Rabbit hearts may differ from human. Acute pretreatment protocol — clinical application timing is challenging."},{"rthcId":"RPEP-00633","title":"Melanocortin receptor agonists, penile erection, and sexual motivation: human studies with Melanotan II.","authors":"Wessells, H; Levine, N; Hadley, M E; Dorr, R; Hruby, V","year":2000,"journal":"International journal of impotence research, 12 Suppl 4, S74-9","doi":null,"pmid":"11035391","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00634","title":"Synergy of L-arginine and GHRP-2 stimulation of growth hormone in men and women: modulation by exercise.","authors":"Wideman, L; Weltman, J Y; Patrie, J T; Bowers, C Y; Shah, N; Story, S; Veldhuis, J D; Weltman, A","year":2000,"journal":"American journal of physiology. Regulatory, integrative and comparative physiology, 279(4), R1467-77","doi":null,"pmid":"11004017","tags":["ghrp","hormone-optimization","clinical-trials"],"studyType":"RCT","evidenceStrength":"strong","keyFinding":"Exercise attenuated L-arginine + GHRP-2 synergistic GH release in men but not women, revealing gender-specific modulation of GH secretagogue synergy by physical activity.","whyItMatters":"Understanding how exercise and gender affect GH secretagogue responses is essential for optimizing GH peptide therapy and interpreting GH stimulation tests in different populations.","specificNumbers":"","methodology":"Randomized study in 9 men and 9 women. L-arginine and GHRP-2 administered alone and together, at rest and after exercise. GH responses measured and compared across conditions and genders.","limitations":"Small sample (9 per gender). Single exercise bout may not reflect chronic training effects. Young healthy volunteers may not represent patient populations."},{"rthcId":"RPEP-00635","title":"Synergy of L-arginine and growth hormone (GH)-releasing peptide-2 on GH release: influence of gender.","authors":"Wideman, L; Weltman, J Y; Patrie, J T; Bowers, C Y; Shah, N; Story, S; Weltman, A; Veldhuis, J D","year":2000,"journal":"American journal of physiology. Regulatory, integrative and comparative physiology, 279(4), R1455-66","doi":null,"pmid":"11004016","tags":["ghrp","hormone-optimization","clinical-trials"],"studyType":"RCT","evidenceStrength":"strong","keyFinding":"L-arginine and GHRP-2 produced synergistic (not just additive) GH release at rest, with women showing greater absolute GH responses than men, supporting combined use for maximal GH stimulation.","whyItMatters":"True synergy means combining two agents produces far more effect than adding their individual effects. For clinical GH stimulation testing or therapy, this combination could maximize GH release at lower doses of each agent.","specificNumbers":"","methodology":"Randomized study in 18 healthy volunteers (9 men, 9 women in early follicular phase). IV L-arginine and GHRP-2 given alone and combined. GH responses compared to assess synergy (versus additivity).","limitations":"Small sample. Young healthy volunteers. IV administration limits practical application. The synergy may not hold at all dose combinations."},{"rthcId":"RPEP-00636","title":"Evaluation of the inactivation of infectious Herpes simplex virus by host-defense peptides.","authors":"Yasin, B; Pang, M; Turner, J S; Cho, Y; Dinh, N N; Waring, A J; Lehrer, R I; Wagar, E A","year":2000,"journal":"European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology, 19(3), 187-94","doi":null,"pmid":"10795591","tags":["antimicrobial-peptides","infection"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Multiple host-defense peptides including lactoferricin and magainin-related peptides directly inactivated HSV-1 and HSV-2 in a validated microplate screening assay, expanding their known antimicrobial spectrum to include antiviral activity.","whyItMatters":"Herpes infections are lifelong and increasingly drug-resistant. Natural antimicrobial peptides with antiviral activity could provide alternative or complementary treatments to existing antivirals.","specificNumbers":"","methodology":"In-vitro antiviral screening using MTT microplate assay on Vero cells. 20 host-defense peptides tested for ability to inactivate HSV-1 and HSV-2. Validated against standard plaque reduction assays.","limitations":"In-vitro virus inactivation may not translate to in-vivo antiviral efficacy. Peptide concentrations required may exceed achievable tissue levels. Mechanism of viral inactivation not determined."},{"rthcId":"RPEP-00637","title":"A randomized, controlled study of thymosin-alpha1 therapy in patients with anti-HBe, HBV-DNA-positive chronic hepatitis B.","authors":"Zavaglia, C; Severini, R; Tinelli, C; Franzone, J S; Airoldi, A; Tempini, S; Bettale, G; Ideo, G","year":2000,"journal":"Digestive diseases and sciences, 45(4), 690-6","doi":null,"pmid":"10759236","tags":["thymosin-alpha-1","infection","clinical-trials"],"studyType":"RCT","evidenceStrength":"moderate","keyFinding":"Thymosin alpha-1 improved virological (HBV DNA clearance) and biochemical (ALT normalization) responses in anti-HBe positive chronic hepatitis B, a treatment-resistant subgroup.","whyItMatters":"Anti-HBe positive hepatitis B has few effective treatments. A peptide immunotherapy that achieves meaningful response rates in this difficult subgroup addresses a significant unmet clinical need.","specificNumbers":"","methodology":"Multicenter randomized controlled trial comparing thymosin alpha-1 to no treatment in anti-HBe, HBV-DNA-positive chronic hepatitis B patients. Six-month treatment course with follow-up monitoring of HBV DNA and liver enzymes.","limitations":"Specific response rates and confidence intervals not detailed in abstract excerpt. Anti-HBe positive HBV is heterogeneous. Long-term durability of response not established in this study."},{"rthcId":"RPEP-00638","title":"Deghenghi 2001 Somatostatin Octapeptides Lanreotide Oct","authors":"","year":2001,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00639","title":"Le Roith 2001 Igf1 And Liver","authors":"","year":2001,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00640","title":"Do growth hormone-releasing peptides act as ghrelin secretagogues?","authors":"Ahnfelt-Rønne, I; Nowak, J; Olsen, U B","year":2001,"journal":"Endocrine, 14(1), 133-5","doi":null,"pmid":"11322495","tags":["ghrp","ipamorelin","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"GHRP-6 and the oral GHS NN703 concentrated in rat gastric tissue containing ghrelin-producing cells, suggesting GH secretagogues may act partly by stimulating endogenous ghrelin release as a secondary mechanism.","whyItMatters":"If GH secretagogues stimulate the body's own ghrelin release, their effects would be more physiological and sustained than simple receptor mimicry, changing how we understand their mechanism.","specificNumbers":"","methodology":"Animal study using radiolabeled GHRP-6 and NN703 for tissue distribution analysis in rats, focusing on gastric tissue accumulation relative to ghrelin-producing cell localization.","limitations":"Tissue distribution doesn't prove ghrelin release stimulation. The stomach accumulation could reflect metabolism or excretion rather than receptor-mediated targeting. Ghrelin release was not directly measured."},{"rthcId":"RPEP-00641","title":"Thymosin alpha-1.","authors":"Ancell, C D; Phipps, J; Young, L","year":2001,"journal":"American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists, 58(10), 879-85; quiz 886-8","doi":null,"pmid":"11381492","tags":["thymosin-alpha-1","immune-function","infection","cancer"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Thymosin alpha-1 demonstrates clinical efficacy in chronic hepatitis B and C (combined with interferon), with emerging evidence for cancer immunotherapy, HIV, and vaccine enhancement, showing excellent tolerability.","whyItMatters":"This review provides the complete clinical picture of thymosin alpha-1 — from mechanism to dosing to efficacy data — serving as the definitive reference for clinical decision-making.","specificNumbers":"","methodology":"Comprehensive drug review covering pharmacology (T-cell, NK cell, cytokine modulation), pharmacokinetics (SC dosing, 2-hour half-life), and clinical trial data across hepatitis, cancer, HIV, and vaccine applications.","limitations":"Clinical data was still accumulating at time of review. Some applications had limited trial sizes. Long-term safety data was emerging. Head-to-head comparisons with newer therapies limited."},{"rthcId":"RPEP-00642","title":"The growth hormone secretagogue ipamorelin counteracts glucocorticoid-induced decrease in bone formation of adult rats.","authors":"Andersen, N B; Malmlöf, K; Johansen, P B; Andreassen, T T; Ørtoft, G; Oxlund, H","year":2001,"journal":"Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society, 11(5), 266-72","doi":null,"pmid":"11735244","tags":["ipamorelin","bone-joint","hormone-optimization"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Three months of ipamorelin (SC injection) counteracted methylprednisolone-induced decreases in bone formation rate, bone mineral content, and partially preserved skeletal muscle mass in adult female rats.","whyItMatters":"Steroid-induced osteoporosis affects millions of patients on chronic corticosteroids. A GH secretagogue that maintains bone formation during steroid therapy could prevent fractures and disability.","specificNumbers":"","methodology":"Animal study in 8-month-old female rats. Groups treated for 3 months with: vehicle, methylprednisolone alone, ipamorelin alone, or methylprednisolone + ipamorelin. Bone formation rate, bone mineral content, and muscle mass measured.","limitations":"Rat study. Three months in rats is relatively long but may not predict lifetime steroid use effects in humans. Adult female rats used; effects may differ by sex and age."},{"rthcId":"RPEP-00643","title":"E2 supplementation selectively relieves GH's autonegative feedback on GH-releasing peptide-2-stimulated GH secretion.","authors":"Anderson, S M; Wideman, L; Patrie, J T; Weltman, A; Bowers, C Y; Veldhuis, J D","year":2001,"journal":"The Journal of clinical endocrinology and metabolism, 86(12), 5904-11","doi":null,"pmid":"11739462","tags":["ghrp","hormone-optimization","fertility"],"studyType":"RCT","evidenceStrength":"moderate","keyFinding":"Estradiol replacement selectively relieved GH autonegative feedback on GHRP-2-stimulated (not GHRH-stimulated) GH secretion in postmenopausal women, demonstrating pathway-specific estrogen modulation of the somatotropic axis.","whyItMatters":"Understanding how estrogen modulates GH feedback is essential for optimizing GH secretagogue therapy in women — particularly postmenopausal women who are most likely to need GH enhancement.","specificNumbers":"","methodology":"RCT in postmenopausal women. Short-term oral estradiol vs placebo. GH feedback tested by pre-infusing GH before GHRP-2 or GHRH stimulation. 10-minute blood sampling with GH deconvolution analysis.","limitations":"Small sample inherent to intensive neuroendocrine studies. Oral estradiol (first-pass liver effects) may differ from transdermal. Short-term estrogen may not reflect chronic use."},{"rthcId":"RPEP-00644","title":"In vitro effect of thymosin-alpha1 and interferon-alpha on Th1 and Th2 cytokine synthesis in patients with chronic hepatitis C.","authors":"Andreone, P; Cursaro, C; Gramenzi, A; Margotti, M; Ferri, E; Talarico, S; Biselli, M; Felline, F; Tuthill, C; Martins, E; Gasbarrini, G; Bernardi, M","year":2001,"journal":"Journal of viral hepatitis, 8(3), 194-201","doi":null,"pmid":"11380797","tags":["thymosin-alpha-1","immune-function","infection"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Thymosin alpha-1 + IFN-alpha shifted Th1/Th2 balance toward Th1 dominance (increased IFN-γ/IL-2, decreased IL-4/IL-10) in HCV patient PBMCs, while IFN-alpha alone produced only partial Th1 enhancement.","whyItMatters":"Hepatitis C persistence is linked to Th2-dominant immune profiles. A therapeutic that shifts this balance toward Th1 could help achieve viral clearance, explaining thymosin alpha-1's clinical benefit.","specificNumbers":"","methodology":"In-vitro study using peripheral blood mononuclear cells from chronic hepatitis C patients. Thymosin alpha-1, IFN-alpha, and their combination tested for Th1 and Th2 cytokine production.","limitations":"In-vitro study; immune cell behavior in culture may differ from in vivo. Patient heterogeneity. The degree of Th1 shift needed for clinical benefit is uncertain."},{"rthcId":"RPEP-00645","title":"Ghrelin is an appetite-stimulatory signal from stomach with structural resemblance to motilin.","authors":"Asakawa, A; Inui, A; Kaga, T; Yuzuriha, H; Nagata, T; Ueno, N; Makino, S; Fujimiya, M; Niijima, A; Fujino, M A; Kasuga, M","year":2001,"journal":"Gastroenterology, 120(2), 337-45","doi":null,"pmid":"11159873","tags":["ghrp","weight-loss","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Ghrelin stimulated food intake and weight gain in rats through vagal and hypothalamic mechanisms, with ghrelin levels suppressed by feeding and increased by leptin, establishing the ghrelin-leptin axis for appetite regulation.","whyItMatters":"Identifying ghrelin as the stomach's hunger signal complemented leptin's satiety signal, completing the peripheral hormonal framework for appetite regulation and opening new obesity treatment targets.","specificNumbers":"","methodology":"Animal study examining ghrelin's effects on food intake, body weight, and interactions with leptin and vagus nerve signaling in rats. Central and peripheral ghrelin administration tested.","limitations":"Rat study. Acute ghrelin effects may differ from chronic signaling. The exact mechanisms of ghrelin-leptin interaction were not fully resolved."},{"rthcId":"RPEP-00646","title":"Neurogenic inflammation in the airways.","authors":"Barnes, P J","year":2001,"journal":"Respiration physiology, 125(1-2), 145-54","doi":null,"pmid":"11240158","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Neuropeptides — particularly tachykinins (substance P, neurokinin A) and calcitonin gene-related peptide (CGRP) — are released from sensory nerves in the airways through axon reflexes and local nerve activation. In rodent models, this neurogenic inflammation clearly contributes to responses against allergens, infections, and irritants. However, direct evidence for sensory neuropeptide involvement in human airway disease is lacking, and initial clinical studies using strategies to block neurogenic inflammation have not shown encouraging results.","whyItMatters":"Asthma and COPD affect hundreds of millions of people worldwide, and many patients remain poorly controlled on existing therapies. If neuropeptide-driven inflammation contributes to these diseases in humans, blocking it could provide new treatment options. This review is important because it honestly assesses both the promise of this pathway and the gap between compelling animal data and disappointing human results.","specificNumbers":"","methodology":"This is a narrative review by P.J. Barnes examining the evidence for neurogenic inflammation in airways across species. It covers in vitro and in vivo animal studies, human tissue data, and early clinical trial results targeting neuropeptide pathways in airway disease.","limitations":"This is a 2001 review and reflects the state of knowledge at that time. The author notes that direct evidence for neuropeptide involvement in human airway disease was limited and clinical trials had been negative. Subsequent research has provided some additional insights but the fundamental translation gap from rodent to human airway neurogenic inflammation persists."},{"rthcId":"RPEP-00647","title":"History about the discovery of the renin-angiotensin system.","authors":"Basso, N; Terragno, N A","year":2001,"journal":"Hypertension (Dallas, Tex. : 1979), 38(6), 1246-9","doi":null,"pmid":"11751697","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00648","title":"A single nucleotide polymorphic mutation in the human mu-opioid receptor severely impairs receptor signaling.","authors":"Befort, K; Filliol, D; Decaillot, F M; Gaveriaux-Ruff, C; Hoehe, M R; Kieffer, B L","year":2001,"journal":"The Journal of biological chemistry, 276(5), 3130-7","doi":null,"pmid":"11067846","tags":["opioid-peptides","receptor-signaling","pain"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"The N40D polymorphism in the human mu-opioid receptor severely impaired beta-endorphin-stimulated G-protein coupling and downstream signaling, potentially explaining ~10% of the population's altered pain sensitivity and opioid drug response.","whyItMatters":"If 10% of people have a weakened natural painkilling receptor, this has massive implications for pain management, addiction risk, and personalized medicine — their endogenous opioid system is inherently less effective.","specificNumbers":"","methodology":"In-vitro study expressing wild-type and N40D variant mu-opioid receptors in cell lines. Receptor signaling (G-protein coupling, cAMP inhibition) measured in response to beta-endorphin and other opioid ligands.","limitations":"In-vitro overexpression study may not perfectly represent in-vivo receptor function. The clinical consequences of the signaling impairment need population-level validation."},{"rthcId":"RPEP-00649","title":"Impaired prohormone convertases in Cpe(fat)/Cpe(fat) mice.","authors":"Berman, Y; Mzhavia, N; Polonskaia, A; Devi, L A","year":2001,"journal":"The Journal of biological chemistry, 276(2), 1466-73","doi":null,"pmid":"11038363","tags":["opioid-peptides","neuropeptides","weight-loss"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"CPE-fat mice showed impaired prohormone convertase activity resulting in defective processing of opioid peptides (prodynorphin, proenkephalin) and other peptide hormones, linking peptide processing dysfunction to obesity.","whyItMatters":"Obesity may not always be about overeating or inactivity — it can result from fundamental defects in how the body processes peptide hormones. This shifts the understanding from behavior to biology.","specificNumbers":"","methodology":"Animal study in CPE-fat/CPE-fat mice analyzing prohormone processing. Multiple peptide precursor and product forms measured in brain and endocrine tissues to assess processing efficiency.","limitations":"Single gene mutation model. CPE-fat mice develop obesity late, suggesting compensatory mechanisms exist. The relative contribution of different peptide processing defects to obesity was not determined."},{"rthcId":"RPEP-00650","title":"Clonal growth inhibition as a bioassay for thymosin alpha1: inactivation of Talpha1 by trifluroacetic acid.","authors":"Bianco-Batlles, D; Naylor, C W; Moshier, J A; Dosescu, J; Naylor, P H","year":2001,"journal":"Cellular and molecular biology (Noisy-le-Grand, France), 47(1), 157-60","doi":null,"pmid":"11292250","tags":["thymosin-alpha-1","cancer","peptide-safety"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"TFA contamination from peptide synthesis inactivated thymosin alpha-1's clonal growth inhibition activity, demonstrating the need for rigorous purification and biological activity testing of therapeutic peptide preparations.","whyItMatters":"If a common synthesis byproduct destroys thymosin alpha-1's activity, then clinical trial results and patient outcomes could vary dramatically based on preparation quality — a serious pharmaceutical concern.","specificNumbers":"","methodology":"In-vitro study developing a clonal growth inhibition bioassay for thymosin alpha-1. Commercial peptide preparations tested with and without TFA contamination. Biological activity correlated with purification quality.","limitations":"Single bioassay for activity assessment. The bioassay measures one activity (growth inhibition) and may not capture all therapeutic actions. TFA levels in specific commercial preparations not quantified."},{"rthcId":"RPEP-00651","title":"Haloperidol-stomach lesions attenuation by pentadecapeptide BPC 157, omeprazole, bromocriptine, but not atropine, lansoprazole, pantoprazole, ranitidine, cimetidine and misoprostol in mice.","authors":"Bilic, I; Zoricic, I; Anic, T; Separovic, J; Stancic-Rokotov, D; Mikus, D; Buljat, G; Ivankovic, D; Aralica, G; Prkacin, I; Perovic, D; Mise, S; Rotkvic, I; Petek, M; Rucman, R; Seiwerth, S; Sikiric, P","year":2001,"journal":"Life sciences, 68(16), 1905-12","doi":null,"pmid":"11292068","tags":["bpc-157","gut-healing","neuroprotection"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"BPC-157, omeprazole, and bromocriptine healed haloperidol-induced gastric lesions, while atropine, lansoprazole, and cimetidine failed, demonstrating the lesions are dopamine-mediated and BPC-157 acts through dopaminergic mechanisms.","whyItMatters":"The selective healing pattern provides the strongest evidence yet that BPC-157 works through dopamine system interaction, not just general cytoprotection or acid reduction.","specificNumbers":"","methodology":"Animal study in rats. Haloperidol-induced gastric lesions treated with BPC-157, omeprazole, bromocriptine, atropine, lansoprazole, or cimetidine. Lesion healing assessed. Prostaglandin and dopamine pathway contributions dissected.","limitations":"Animal study. The specific dopamine receptor subtypes involved were not determined. Omeprazole's healing may work through a non-acid mechanism in this model."},{"rthcId":"RPEP-00652","title":"The important role of neuropeptides in complex regional pain syndrome.","authors":"Birklein, F; Schmelz, M; Schifter, S; Weber, M","year":2001,"journal":"Neurology, 57(12), 2179-84","doi":null,"pmid":"11756594","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00653","title":"Methionine-enkephalin-and Dynorphin A-release from immune cells and control of inflammatory pain.","authors":"Cabot, Peter J; Carter, Laurenda; Schäfer, Michael; Stein, Christoph","year":2001,"journal":"Pain, 93(3), 207-212","doi":"10.1016/S0304-3959(01)00322-0","pmid":"11514079","tags":["opioid-peptides","pain","immune-function","inflammation"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Immune cells at sites of inflammation contain and release met-enkephalin, dynorphin A, and beta-endorphin, which activate peripheral opioid receptors on sensory nerves to provide local inflammatory pain control.","whyItMatters":"Local pain control by immune cells avoids the side effects of brain-acting painkillers. Enhancing this natural peripheral opioid system could provide effective pain relief without sedation, addiction, or respiratory depression.","specificNumbers":"","methodology":"Animal study in rats with CFA-induced paw inflammation. Immune cells from inflamed tissue tested for opioid peptide content (RIA) and release (stimulation assays). Pain behavior correlated with local opioid receptor activation.","limitations":"Rat inflammation model. The quantity of opioid released may not be sufficient for complete pain control. Human immune cell opioid release may differ quantitatively."},{"rthcId":"RPEP-00654","title":"Identification, characterization, and biological activity of specific receptors for natural (ghrelin) and synthetic growth hormone secretagogues and analogs in human breast carcinomas and cell lines.","authors":"Cassoni, P; Papotti, M; Ghè, C; Catapano, F; Sapino, A; Graziani, A; Deghenghi, R; Reissmann, T; Ghigo, E; Muccioli, G","year":2001,"journal":"The Journal of clinical endocrinology and metabolism, 86(4), 1738-45","doi":null,"pmid":"11297611","tags":["ghrp","cancer","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Functional ghrelin and synthetic GHS receptors were identified on human breast, prostate, and lung cancer cells, with receptor subtypes potentially different from those in normal pituitary tissue.","whyItMatters":"If cancer cells respond to ghrelin and GH secretagogues, this has dual implications: potential cancer therapeutic targets AND safety concerns for people using GH peptides.","specificNumbers":"","methodology":"In-vitro binding study using radioligands on human cancer cell lines (breast, prostate, lung). Binding competition with ghrelin and synthetic GHS. Functional signaling assessed by second messenger assays.","limitations":"In-vitro cancer cell line study. Receptor presence doesn't determine whether activation promotes or inhibits cancer growth. Cell lines may not represent primary tumors."},{"rthcId":"RPEP-00655","title":"Circulating natriuretic peptide concentrations in patients with end-stage renal disease: role of brain natriuretic peptide as a biomarker for ventricular remodeling.","authors":"Cataliotti, A; Malatino, L S; Jougasaki, M; Zoccali, C; Castellino, P; Giacone, G; Bellanuova, I; Tripepi, R; Seminara, G; Parlongo, S; Stancanelli, B; Bonanno, G; Fatuzzo, P; Rapisarda, F; Belluardo, P; Signorelli, S S; Heublein, D M; Lainchbury, J G; Leskinen, H K; Bailey, K R; Redfield, M M; Burnett, J C","year":2001,"journal":"Mayo Clinic proceedings, 76(11), 1111-9","doi":null,"pmid":"11702899","tags":["natriuretic-peptides","cardiovascular","kidney"],"studyType":"cross-sectional","evidenceStrength":"moderate","keyFinding":"BNP was the strongest predictor of left ventricular hypertrophy and cardiac mortality in 112 ESRD dialysis patients, outperforming ANP for cardiovascular risk stratification in this high-risk population.","whyItMatters":"Dialysis patients have a 10-30x higher cardiovascular mortality than the general population. A simple blood test that identifies the highest-risk patients enables targeted preventive interventions.","specificNumbers":"","methodology":"Cross-sectional cohort study in 112 dialysis patients. Plasma BNP, ANP, and N-terminal ANP measured. Echocardiography assessed LVH. Cardiac mortality tracked during follow-up.","limitations":"Cross-sectional study with follow-up. Dialysis timing relative to blood sampling can affect peptide levels. Specific BNP cutoff values for this population may differ from general cardiac patients."},{"rthcId":"RPEP-00656","title":"The small subunit of the mammalian mitochondrial ribosome. Identification of the full complement of ribosomal proteins present.","authors":"Cavdar Koc, E; Burkhart, W; Blackburn, K; Moseley, A; Spremulli, L L","year":2001,"journal":"The Journal of biological chemistry, 276(22), 19363-74","doi":null,"pmid":"11279123","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00657","title":"Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebo-controlled study.","authors":"Channick, R N; Simonneau, G; Sitbon, O; Robbins, I M; Frost, A; Tapson, V F; Badesch, D B; Roux, S; Rainisio, M; Bodin, F; Rubin, L J","year":2001,"journal":"Lancet (London, England), 358(9288), 1119-23","doi":null,"pmid":"11597664","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00658","title":"Endogenous natriuretic peptides participate in renal and humoral actions of acute vasopeptidase inhibition in experimental mild heart failure.","authors":"Chen, H H; Lainchbury, J G; Matsuda, Y; Harty, G J; Burnett, J C","year":2001,"journal":"Hypertension (Dallas, Tex. : 1979), 38(2), 187-91","doi":null,"pmid":"11509474","tags":["natriuretic-peptides","cardiovascular"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Acute vasopeptidase inhibition in experimental mild heart failure raised ANP/BNP, increased renal sodium excretion, suppressed aldosterone, and avoided renin-angiotensin activation — harnessing endogenous peptide defenses.","whyItMatters":"Treating early heart failure by boosting the body's own protective peptides is more physiological than adding external drugs. This approach formed the basis for sacubitril/valsartan (Entresto).","specificNumbers":"","methodology":"Animal study in dogs with pacing-induced mild heart failure. Vasopeptidase inhibitor administered acutely. ANP, BNP, renal function, renin, and aldosterone measured before and after.","limitations":"Animal model. Acute single-dose study. Mild heart failure — effects may differ in severe HF. Long-term effects not assessed."},{"rthcId":"RPEP-00659","title":"Disulfide bond formation in peptides.","authors":"Chen, Lin; Annis, Ioana; Barany, George","year":2001,"journal":"Current protocols in protein science, Chapter 18, 18.6.1-18.6.19","doi":"10.1002/0471140864.ps1806s23","pmid":"18429142","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00660","title":"Effects of oral administration of ibutamoren mesylate, a nonpeptide growth hormone secretagogue, on the growth hormone-insulin-like growth factor I axis in growth hormone-deficient children.","authors":"Codner, E; Cassorla, F; Tiulpakov, A N; Mericq, M V; Avila, A; Pescovitz, O H; Svensson, J; Cerchio, K; Krupa, D; Gertz, B J; Murphy, G","year":2001,"journal":"Clinical pharmacology and therapeutics, 70(1), 91-8","doi":null,"pmid":"11452249","tags":["mk-677","hormone-optimization","clinical-trials"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"MK-677 at 10 and 25 mg/day increased GH and IGF-1 dose-dependently over 4 weeks in GH-deficient adults with acceptable safety, supporting its potential as oral GH replacement therapy.","whyItMatters":"Adults with GH deficiency currently need daily injections. An oral alternative that safely restores GH and IGF-1 levels would dramatically improve treatment convenience and compliance.","specificNumbers":"","methodology":"Open-label clinical trial evaluating MK-677 at 10 and 25 mg/day for 4 weeks in adults with GH deficiency. GH profiles, IGF-1, safety parameters, and tolerability assessed.","limitations":"Open-label (no placebo). 4 weeks may not predict long-term efficacy or safety. Whether the GH/IGF-1 increases translate to clinical benefit was not assessed."},{"rthcId":"RPEP-00661","title":"Vasopeptidase inhibitors: a new therapeutic concept in cardiovascular disease?","authors":"Corti, R; Burnett, J C; Rouleau, J L; Ruschitzka, F; Lüscher, T F","year":2001,"journal":"Circulation, 104(15), 1856-62","doi":null,"pmid":"11591626","tags":["natriuretic-peptides","cardiovascular"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Vasopeptidase inhibitors simultaneously enhance protective natriuretic peptides/bradykinin and block harmful angiotensin II, showing superior cardiovascular benefits over ACE inhibitors alone, despite angioedema risk as a limitation.","whyItMatters":"This dual approach to cardiovascular therapy — boost protection AND block harm simultaneously — has proven transformative, evolving into the sacubitril/valsartan (Entresto) concept now saving lives worldwide.","specificNumbers":"","methodology":"Comprehensive review of vasopeptidase inhibitor pharmacology, clinical trial data, and therapeutic potential for hypertension and heart failure.","limitations":"First-generation vasopeptidase inhibitors (omapatrilat) had angioedema risk. The review preceded sacubitril/valsartan's success in avoiding this limitation."},{"rthcId":"RPEP-00662","title":"Somatostatin octapeptides (lanreotide, octreotide, vapreotide, and their analogs) share the growth hormone-releasing peptide receptor in the human pituitary gland.","authors":"Deghenghi, R; Papotti, M; Ghigo, E; Muccioli, G; Locatelli, V","year":2001,"journal":"Endocrine, 14(1), 29-33","doi":null,"pmid":"11322499","tags":["ghrp","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Somatostatin octapeptides (lanreotide, octreotide, vapreotide) showed significant binding to GHRP receptors in human pituitary membranes, revealing unexpected cross-reactivity between somatostatin and GH secretagogue receptor systems.","whyItMatters":"Millions of patients take somatostatin analogs for acromegaly and neuroendocrine tumors. Cross-binding to GHRP receptors could explain unexpected clinical effects or drug interactions.","specificNumbers":"","methodology":"In-vitro binding study using radiolabeled ligands on human pituitary membranes. Binding competition between somatostatin analogs, SRIF-14, and GHRP compounds at both SRIF and GHRP receptor subtypes.","limitations":"In-vitro binding on tissue membranes. Clinical significance of the cross-binding is uncertain. Binding doesn't prove functional activation or inhibition at GHRP receptors."},{"rthcId":"RPEP-00663","title":"Opioid peptides attenuate blood pressure increase in acute respiratory failure.","authors":"Fontana, F; Bernardi, P; Tartuferi, L; Boschi, S; Di Toro, R; Spampinato, S","year":2001,"journal":"Peptides, 22(4), 631-7","doi":null,"pmid":"11311734","tags":["opioid-peptides","respiratory","cardiovascular"],"studyType":"cross-sectional","evidenceStrength":"moderate","keyFinding":"Elevated plasma beta-endorphin and met-enkephalin in COPD patients with acute respiratory failure inversely correlated with blood pressure, demonstrating endogenous opioid-mediated attenuation of the hypertensive stress response.","whyItMatters":"Understanding that opioid peptides naturally buffer blood pressure during respiratory crises helps explain cardiovascular events in COPD and informs management of these critically ill patients.","specificNumbers":"","methodology":"Cross-sectional study in 24 COPD patients with acute respiratory failure. Plasma opioid peptides, norepinephrine, ANP, and blood pressure measured and correlated.","limitations":"Cross-sectional correlational design. 24 patients. The causal direction of the opioid-blood pressure relationship cannot be determined. Opioid measurements at one timepoint."},{"rthcId":"RPEP-00664","title":"Chemopreventive property of a soybean peptide (lunasin) that binds to deacetylated histones and inhibits acetylation.","authors":"Galvez, A F; Chen, N; Macasieb, J; de Lumen, B O","year":2001,"journal":"Cancer research, 61(20), 7473-8","doi":null,"pmid":"11606382","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00665","title":"Plasma pro-brain natriuretic peptides are strong biochemical markers in clinical cardiology.","authors":"Gøtze, J P; Kastrup, J","year":2001,"journal":"Scandinavian journal of clinical and laboratory investigation. Supplementum, 234, 47-51","doi":null,"pmid":"11713980","tags":["natriuretic-peptides","cardiovascular"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Pro-BNP and NT-proBNP are strong biochemical markers for heart failure with practical advantages over mature BNP, including longer stability and higher circulating levels, supporting their clinical adoption.","whyItMatters":"The choice between BNP and NT-proBNP assays affects clinical decision-making. Understanding their relative advantages helps clinicians and laboratories choose the optimal test.","specificNumbers":"","methodology":"Review of proBNP biochemistry, assay development, and clinical validation studies across heart failure, ACS, and cardiovascular screening applications.","limitations":"Review from early in NT-proBNP's clinical adoption. Optimal cutoff values were still being refined. Assay standardization was incomplete."},{"rthcId":"RPEP-00666","title":"Highly potent growth hormone secretagogues: hybrids of NN703 and ipamorelin.","authors":"Hansen, T K; Ankersen, M; Raun, K; Hansen, B S","year":2001,"journal":"Bioorganic & medicinal chemistry letters, 11(14), 1915-8","doi":null,"pmid":"11459660","tags":["ipamorelin","ghrp","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"NN703-ipamorelin hybrid GH secretagogues showed low nanomolar in vitro potency in pituitary cell assays and effective GH release in pigs in vivo, validating the hybrid design approach.","whyItMatters":"Creating more potent oral GH secretagogues is key to developing practical GH deficiency treatments. Combining proven scaffolds is an efficient drug design strategy.","specificNumbers":"","methodology":"In-vitro pituitary cell assay (rat) and in-vivo single-dose GH release testing in pigs for a series of NN703-ipamorelin hybrid compounds.","limitations":"Short abstract with limited pharmacological detail. Single-dose pig study. Oral bioavailability not confirmed for all hybrids."},{"rthcId":"RPEP-00667","title":"Plasma growth hormone (GH) responses after administration of the peptidergic GH secretagogue KP102 into the oral cavity, rumen, abomasum and duodenum in adult goats.","authors":"Hashizume, T; Tanabe, Y; Ohtsuki, K; Mori, A; Matsumoto, N; Hara, S","year":2001,"journal":"Domestic animal endocrinology, 20(1), 37-46","doi":null,"pmid":"11164332","tags":["ghrp","hormone-optimization","oral-peptides"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Oral GHRP-2 stimulated GH release in adult goats when absorbed through the intestines (not rumen), demonstrating post-gastric oral peptide bioactivity in adult large animals with mature digestive systems.","whyItMatters":"Oral peptide delivery is the holy grail of peptide therapeutics. Showing it works in adult goats with complex digestive systems brings oral peptide drugs closer to practical reality.","specificNumbers":"","methodology":"Animal study in adult goats. GHRP-2 administered orally, directly into the rumen, or into the intestines via fistulae. Plasma GH measured after each route to determine absorption site.","limitations":"Goat ruminant digestive system differs from human. High doses still required. Oral bioavailability as a percentage was not precisely quantified."},{"rthcId":"RPEP-00668","title":"Peripheral signals conveying metabolic information to the brain: short-term and long-term regulation of food intake and energy homeostasis.","authors":"Havel, P J","year":2001,"journal":"Experimental biology and medicine (Maywood, N.J.), 226(11), 963-77","doi":null,"pmid":"11743131","tags":["neuropeptides","weight-loss","receptor-signaling"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Appetite regulation involves two integrated time scales: acute meal-by-meal gut peptide signals (CCK, GLP-1, ghrelin, PYY) and chronic body weight signals (leptin, insulin), converging on hypothalamic and brainstem integration centers.","whyItMatters":"Effective obesity treatment may require targeting both short-term (meal) and long-term (body weight) regulatory systems. Understanding this dual-time-scale architecture guides combination therapy development.","specificNumbers":"","methodology":"Comprehensive review of peripheral metabolic signaling in food intake regulation, covering gut peptides, adiposity signals, and their central integration pathways.","limitations":"Review from 2001. The rapid advances in GLP-1-based obesity drugs since then have validated some predictions while complicating others."},{"rthcId":"RPEP-00669","title":"The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism following chronic treatment in obese mice and beta(3)-AR knock-out mice.","authors":"Heffernan, M; Summers, R J; Thorburn, A; Ogru, E; Gianello, R; Jiang, W J; Ng, F M","year":2001,"journal":"Endocrinology, 142(12), 5182-9","doi":null,"pmid":"11713213","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00670","title":"Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragment.","authors":"Heffernan, M A; Thorburn, A W; Fam, B; Summers, R; Conway-Campbell, B; Waters, M J; Ng, F M","year":2001,"journal":"International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity, 25(10), 1442-9","doi":null,"pmid":"11673763","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00671","title":"Heart failure and neuroendocrine activation: diagnostic, prognostic and therapeutic perspectives.","authors":"Kjaer, A; Hesse, B","year":2001,"journal":"Clinical physiology (Oxford, England), 21(6), 661-72","doi":null,"pmid":"11722473","tags":["natriuretic-peptides","cardiovascular"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Heart failure involves coordinated activation of multiple neurohormonal systems, and measuring these provides diagnostic, prognostic, and therapeutic guidance, with BNP/NT-proBNP showing the strongest clinical utility.","whyItMatters":"Heart failure management increasingly relies on biomarker-guided therapy. Understanding which hormones to measure and what their levels mean improves clinical decision-making across the disease spectrum.","specificNumbers":"","methodology":"Comprehensive review of neuroendocrine activation in heart failure, covering pathophysiology, diagnostic utility, prognostic value, and treatment implications of multiple hormonal systems.","limitations":"Review from 2001. Some neurohormonal targets described have not yet yielded successful therapies (vasopressin, endothelin in chronic HF). Treatment guidelines have evolved."},{"rthcId":"RPEP-00672","title":"The role of adrenomedullin in producing differential hemodynamic responses during sepsis.","authors":"Koo, D J; Zhou, M; Chaudry, I H; Wang, P","year":2001,"journal":"The Journal of surgical research, 95(2), 207-18","doi":null,"pmid":"11162047","tags":["neuropeptides","inflammation","cardiovascular"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Adrenomedullin contributes to both phases of sepsis: beneficial vasodilation during early compensation and harmful cardiovascular collapse during late decompensation, driven by progressive ADM accumulation from reduced clearance and increased tissue production.","whyItMatters":"Understanding the dual role of ADM in sepsis — helpful early, harmful late — could guide timing of potential ADM-modulating therapies to preserve early benefits while preventing late collapse.","specificNumbers":"","methodology":"Review synthesizing data on adrenomedullin dynamics during experimental sepsis, covering tissue production, pulmonary clearance, receptor regulation, and hemodynamic effects across both sepsis phases.","limitations":"Review based largely on animal sepsis models. The exact tipping point where ADM shifts from beneficial to harmful is not precisely defined."},{"rthcId":"RPEP-00673","title":"Rostral ventrolateral medullary opioid receptor subtypes in the inhibitory effect of electroacupuncture on reflex autonomic response in cats.","authors":"Li, P; Tjen-A-Looi, S; Longhurst, J C","year":2001,"journal":"Autonomic neuroscience : basic & clinical, 89(1-2), 38-47","doi":null,"pmid":"11474645","tags":["opioid-peptides","pain","cardiovascular"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Electroacupuncture inhibited cardiovascular pressor reflexes through mu and delta (not kappa) opioid receptors in the RVLM, demonstrating endogenous opioid peptide release in the brain's blood pressure control center.","whyItMatters":"Providing a precise neural mechanism for acupuncture's blood pressure effects validates this ancient practice scientifically and identifies specific molecular targets for cardiovascular neuromodulation.","specificNumbers":"","methodology":"Animal study using microinjection of selective opioid receptor antagonists into the RVLM during electroacupuncture. Cardiovascular pressor reflex measured with and without opioid receptor blockade.","limitations":"Animal study with direct brain microinjection — not clinically translatable. The specific opioid peptides released (enkephalins vs endorphins) were not identified."},{"rthcId":"RPEP-00674","title":"Efficacy of a growth hormone-releasing peptide mimetic in cardiac ischemia/reperfusion injury.","authors":"MacAndrew, J T; Ellery, S S; Parry, M A; Pan, L C; Black, S C","year":2001,"journal":"European journal of pharmacology, 432(2-3), 195-202","doi":null,"pmid":"11740956","tags":["ghrp","cardiovascular"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Oral CP-424,391 (25 mg/kg/day for 7 days) reduced myocardial infarct size by ~50% in an in-vivo rabbit ischemia-reperfusion model, demonstrating significant cardioprotection from an orally available GH secretagogue.","whyItMatters":"An oral pill that halves heart attack damage would be a major medical advance. This proof-of-concept shows GH secretagogues can achieve this through their cardiac receptor (independent of GH release).","specificNumbers":"","methodology":"Animal study in rabbits. CP-424,391 administered orally for 7 days before ischemia-reperfusion. Infarct size measured by TTC staining as percentage of area at risk.","limitations":"Rabbit model. Pre-treatment design (7 days before ischemia) — clinical application would require chronic preventive use. The specific mechanism (cardiac GHS-R vs systemic effects) was not dissected."},{"rthcId":"RPEP-00675","title":"Long-term treatment with neutral endopeptidase inhibitor improves cardiac function and reduces natriuretic peptides in rats with chronic heart failure.","authors":"Maki, T; Nasa, Y; Yamaguchi, F; Yoshida, H; Mori, M; Takada, T; Horikawa, E; Okano, K; Takeo, S","year":2001,"journal":"Cardiovascular research, 51(3), 608-17","doi":null,"pmid":"11476752","tags":["natriuretic-peptides","cardiovascular"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Long-term NEP inhibition (2 weeks) in heart failure rats improved cardiac function, reduced ventricular remodeling, and paradoxically lowered ANP/BNP — the decrease reflecting improved cardiac status rather than drug failure.","whyItMatters":"The paradoxical BNP decrease during NEP inhibition initially confused clinicians. This study explains it: successful treatment reduces cardiac stress, which lowers BNP even though the drug prevents BNP breakdown.","specificNumbers":"","methodology":"Animal study in rats with experimental heart failure. Chronic NEP inhibitor treatment for 2 weeks. Cardiac function (echocardiography), ventricular mass, and plasma ANP/BNP measured.","limitations":"Rat heart failure model. 2-week treatment is relatively short. The paradoxical peptide response may differ by heart failure severity."},{"rthcId":"RPEP-00676","title":"Structural similarity of ghrelin derivatives to peptidyl growth hormone secretagogues.","authors":"Matsumoto, M; Kitajima, Y; Iwanami, T; Hayashi, Y; Tanaka, S; Minamitake, Y; Hosoda, H; Kojima, M; Matsuo, H; Kangawa, K","year":2001,"journal":"Biochemical and biophysical research communications, 284(3), 655-9","doi":null,"pmid":"11396951","tags":["ghrp","peptide-design","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Optimized ghrelin tetrapeptide derivatives showed structural similarity to synthetic peptidyl GH secretagogues like GHRP-1, demonstrating convergent molecular solutions between the natural ligand and designed drugs.","whyItMatters":"Structural convergence between ghrelin and synthetic GH secretagogues validates decades of drug design and provides insights for creating optimized hybrid molecules.","specificNumbers":"","methodology":"In-vitro structure-activity study. Modified ghrelin N-terminal tetrapeptides were synthesized and tested for GHS-R binding and activation, with structural comparison to known peptidyl GH secretagogues.","limitations":"In-vitro receptor binding and activation. Structural similarity at the receptor level doesn't guarantee similar pharmacokinetics or in-vivo effects."},{"rthcId":"RPEP-00677","title":"Co-expression of urotensin II and its receptor (GPR14) in human cardiovascular and renal tissues.","authors":"Matsushita, M; Shichiri, M; Imai, T; Iwashina, M; Tanaka, H; Takasu, N; Hirata, Y","year":2001,"journal":"Journal of hypertension, 19(12), 2185-90","doi":null,"pmid":"11725162","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00678","title":"Left ventricular dysfunction, natriuretic peptides, and mortality in an urban population.","authors":"McDonagh, T A; Cunningham, A D; Morrison, C E; McMurray, J J; Ford, I; Morton, J J; Dargie, H J","year":2001,"journal":"Heart (British Cardiac Society), 86(1), 21-6","doi":null,"pmid":"11410555","tags":["natriuretic-peptides","cardiovascular"],"studyType":"cohort","evidenceStrength":"strong","keyFinding":"In 1,640 randomly sampled urban adults, BNP predicted mortality from left ventricular dysfunction, supporting population-level screening with natriuretic peptides to identify undiagnosed cardiac disease.","whyItMatters":"Many people have undiagnosed heart weakness. A cheap blood test that identifies them before they develop heart failure symptoms could save lives through early treatment — the case for population screening.","specificNumbers":"","methodology":"Population-based cohort study. 1,640 random urban residents aged 25-74. Echocardiography for LV function, plasma natriuretic peptides measured, mortality tracked during follow-up.","limitations":"Single urban population. Specific BNP cutoffs for population screening not established. Cost-effectiveness of mass screening not assessed. Follow-up duration not detailed."},{"rthcId":"RPEP-00679","title":"Pentadecapeptide BPC 157 cream improves burn-wound healing and attenuates burn-gastric lesions in mice.","authors":"Mikus, D; Sikiric, P; Seiwerth, S; Petricevic, A; Aralica, G; Druzijancic, N; Rucman, R; Petek, M; Pigac, B; Perovic, D; Kolombo, M; Kokic, N; Mikus, S; Duplancic, B; Fattorini, I; Turkovic, B; Rotkvic, I; Mise, S; Prkacin, I; Konjevoda, P; Stambuk, N; Anic, T","year":2001,"journal":"Burns : journal of the International Society for Burn Injuries, 27(8), 817-27","doi":null,"pmid":"11718984","tags":["bpc-157","wound-healing","gut-healing"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Topical BPC-157 cream accelerated burn wound healing (faster re-epithelialization and contraction) while simultaneously attenuating distant burn-associated gastric lesions in mice, demonstrating both local and systemic effects from topical application.","whyItMatters":"Burns cause multi-organ damage. A topical cream that heals the burn AND protects internal organs represents a fundamentally different approach to burn care — treating the systemic injury, not just the wound.","specificNumbers":"","methodology":"Animal study in mice with standardized burn wounds. BPC-157 applied topically as cream or systemically (IP). Burn wound healing measured by planimetry. Gastric lesions scored. Multiple timepoints assessed.","limitations":"Mouse burn model. Small burn area relative to body surface. The mechanism of systemic absorption and gastric protection from topical application was not determined."},{"rthcId":"RPEP-00680","title":"Relationship among plasma cortisol, catecholamines, neuropeptide Y, and human performance during exposure to uncontrollable stress.","authors":"Morgan, C A; Wang, S; Rasmusson, A; Hazlett, G; Anderson, G; Charney, D S","year":2001,"journal":"Psychosomatic medicine, 63(3), 412-22","doi":null,"pmid":"11382268","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00681","title":"Binding of 125I-labeled ghrelin to membranes from human hypothalamus and pituitary gland.","authors":"Muccioli, G; Papotti, M; Locatelli, V; Ghigo, E; Deghenghi, R","year":2001,"journal":"Journal of endocrinological investigation, 24(3), RC7-9","doi":null,"pmid":"11314756","tags":["ghrp","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"125I-ghrelin bound to human hypothalamus and pituitary with high affinity but showed different binding characteristics than synthetic GHS (hexarelin, MK-0677), suggesting distinct receptor interaction modes or subtypes.","whyItMatters":"If ghrelin and synthetic GH secretagogues bind differently, they could have distinct therapeutic profiles. This explains why ghrelin (appetite + GH) and some synthetic GHS (GH-selective like ipamorelin) have different effect spectra.","specificNumbers":"","methodology":"In-vitro binding study using 125I-labeled ghrelin on human hypothalamic and pituitary membrane preparations. Competition binding with unlabeled ghrelin, hexarelin, and MK-0677 to characterize binding sites.","limitations":"In-vitro binding on post-mortem tissue. Binding differences don't conclusively prove separate receptor subtypes. Human tissue availability limits sample size."},{"rthcId":"RPEP-00682","title":"Effect of alendronate and MK-677 (a growth hormone secretagogue), individually and in combination, on markers of bone turnover and bone mineral density in postmenopausal osteoporotic women.","authors":"Murphy, M G; Weiss, S; McClung, M; Schnitzer, T; Cerchio, K; Connor, J; Krupa, D; Gertz, B J","year":2001,"journal":"The Journal of clinical endocrinology and metabolism, 86(3), 1116-25","doi":null,"pmid":"11238495","tags":["mk-677","bone-joint","clinical-trials"],"studyType":"RCT","evidenceStrength":"moderate","keyFinding":"MK-677 combined with alendronate maintained higher bone formation markers than alendronate alone over 12 months in postmenopausal women, demonstrating complementary mechanisms: IGF-1-stimulated bone building plus anti-resorptive bone protection.","whyItMatters":"Current osteoporosis drugs are mainly anti-resorptive (they slow bone loss). Adding a bone-building agent could produce superior outcomes. This study demonstrates the principle with an oral GH secretagogue.","specificNumbers":"","methodology":"Randomized, double-blind, placebo-controlled study. Postmenopausal women received: MK-677 25mg/day, alendronate 10mg/day, combination, or placebo for 12 months. Bone turnover markers, BMD, IGF-1 measured.","limitations":"Bone turnover markers are surrogates — actual fracture prevention not assessed. 12 months may not predict long-term bone density outcomes. Sample size details not in abstract."},{"rthcId":"RPEP-00683","title":"Pharmacological profile of a new orally active growth hormone secretagogue, SM-130686.","authors":"Nagamine, J; Nagata, R; Seki, H; Nomura-Akimaru, N; Ueki, Y; Kumagai, K; Taiji, M; Noguchi, H","year":2001,"journal":"The Journal of endocrinology, 171(3), 481-9","doi":null,"pmid":"11739014","tags":["ghrp","peptide-design","hormone-optimization"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"SM-130686, a structurally novel oxindole GH secretagogue, showed potent in-vitro and in-vivo GH-releasing activity, increased IGF-1 and body weight in rats, and was orally active, demonstrating a new chemical class for GHS-R targeting.","whyItMatters":"Having structurally diverse drugs for the same target provides backup options if one class has safety issues, and may reveal compounds with better selectivity or pharmacokinetics.","specificNumbers":"","methodology":"Preclinical pharmacology study. SM-130686 tested in rat pituitary cell assays (in vitro), acute GH release in rats and dogs (in vivo), and chronic dosing for body weight and IGF-1 effects.","limitations":"Preclinical data only. Selectivity profile not fully characterized. Long-term safety unknown. No human data."},{"rthcId":"RPEP-00684","title":"Chronic administration of ghrelin improves left ventricular dysfunction and attenuates development of cardiac cachexia in rats with heart failure.","authors":"Nagaya, N; Uematsu, M; Kojima, M; Ikeda, Y; Yoshihara, F; Shimizu, W; Hosoda, H; Hirota, Y; Ishida, H; Mori, H; Kangawa, K","year":2001,"journal":"Circulation, 104(12), 1430-5","doi":null,"pmid":"11560861","tags":["ghrelin","heart-failure","cardiac-cachexia"],"studyType":"Preclinical (Animal Study)","evidenceStrength":"Moderate","keyFinding":"Three weeks of twice-daily ghrelin injections improved multiple measures of heart function in rats with heart failure caused by coronary artery ligation. Ghrelin-treated heart failure rats had significantly higher cardiac output (315 vs 266 mL/min/kg, P<0.05), stronger heart contractions (dP/dtmax 5,738 vs 4,363 mmHg/s, P<0.05), and improved fractional shortening (19% vs 15%, P<0.05) compared to placebo-treated heart failure rats.\n\nGhrelin also attenuated cardiac cachexia — the dangerous muscle wasting that accompanies heart failure. Treated rats gained 10% body weight versus only 3% for placebo. Additionally, ghrelin inhibited left ventricular enlargement (remodeling) and increased the thickness of surviving heart muscle. These benefits occurred alongside significantly elevated growth hormone and IGF-1 levels.","whyItMatters":"This 2001 Circulation paper is one of the earliest and most influential studies demonstrating ghrelin's cardioprotective effects. Published just two years after ghrelin's discovery, it showed that the hunger hormone does far more than stimulate appetite — it directly improves failing heart function and prevents the muscle wasting that kills many heart failure patients. The results were published in Circulation, one of the top cardiology journals, and launched an entire research field exploring ghrelin-based cardiac therapies.","specificNumbers":"100 μg/kg SC twice daily · 3 weeks · cardiac output 315 vs 266 mL/min/kg (P<.05) · dP/dtmax 5,738 vs 4,363 mmHg/s (P<.05) · fractional shortening 19% vs 15% (P<.05) · body weight +10% vs +3% (P<.05) · GH and IGF-1 significantly elevated","methodology":"Rats underwent left coronary artery ligation or sham surgery. Four weeks after surgery (allowing heart failure to develop), rats received rat ghrelin (100 μg/kg subcutaneously twice daily) or saline for 3 weeks. Assessment included echocardiography, cardiac catheterization for hemodynamic measurements, serum GH and IGF-1 levels, and body weight monitoring.","limitations":"This is a rat study using surgically-induced heart failure (coronary ligation), which models post-infarction cardiomyopathy but may not represent all forms of human heart failure. The 3-week treatment period is short. Ghrelin's effects may be partly mediated through GH/IGF-1 elevation, which raises theoretical long-term safety concerns. The twice-daily injection regimen would be impractical for clinical use without longer-acting formulations. Specific group sizes are not provided in the abstract."},{"rthcId":"RPEP-00685","title":"Hemodynamic, renal, and hormonal effects of ghrelin infusion in patients with chronic heart failure.","authors":"Nagaya, N; Miyatake, K; Uematsu, M; Oya, H; Shimizu, W; Hosoda, H; Kojima, M; Nakanishi, N; Mori, H; Kangawa, K","year":2001,"journal":"The Journal of clinical endocrinology and metabolism, 86(12), 5854-9","doi":null,"pmid":"11739451","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 12 patients with chronic heart failure, IV ghrelin infusion at 0.1 µg/kg/min produced significant hemodynamic improvements compared to placebo:\n\n• Mean arterial pressure decreased by 9 mmHg (p<0.05)\n• Cardiac index increased by 25% (p<0.05)\n• Stroke volume index increased by 30% (p<0.05)\n• Heart rate did not significantly change\n• Pulmonary arterial pressure and pulmonary capillary wedge pressure were not significantly altered\n\nGhrelin also triggered a 15-fold increase in serum growth hormone levels, with slight increases in epinephrine, ACTH, cortisol, and prolactin. Kidney function markers — urine volume, sodium excretion, and creatinine clearance — were unaffected. Placebo infusion produced no changes in any parameter.","whyItMatters":"Heart failure treatments that improve cardiac output without worsening kidney function or raising heart rate are highly valuable. This early study showed ghrelin could do exactly that, suggesting this peptide might have therapeutic potential for heart failure beyond its well-known roles in appetite and growth hormone regulation. It opened a new avenue of cardiovascular peptide research.","specificNumbers":"","methodology":"This was a double-blind, placebo-controlled study in 12 patients with chronic heart failure. Each patient received either an intravenous infusion of synthetic human ghrelin (0.1 µg/kg/min) or placebo. Researchers measured hemodynamic parameters (blood pressure, cardiac index, stroke volume, pulmonary pressures), renal function (urine volume, sodium excretion, creatinine clearance), and hormonal responses (GH, epinephrine, ACTH, cortisol, prolactin) during and after infusion.","limitations":"The study included only 12 patients, which limits statistical power and generalizability. It measured acute effects of a single infusion rather than long-term outcomes. The study did not investigate the mechanism behind ghrelin's hemodynamic effects or whether repeated dosing would sustain benefits. As a 2001 study, newer heart failure treatments have since emerged that may change the clinical context."},{"rthcId":"RPEP-00686","title":"Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis.","authors":"Neer, R M; Arnaud, C D; Zanchetta, J R; Prince, R; Gaich, G A; Reginster, J Y; Hodsman, A B; Eriksen, E F; Ish-Shalom, S; Genant, H K; Wang, O; Mitlak, B H","year":2001,"journal":"The New England journal of medicine, 344(19), 1434-41","doi":null,"pmid":"11346808","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 1,637 postmenopausal women with prior vertebral fractures treated for a median of 21 months:\n\n**Fracture reduction:**\n- New vertebral fractures: 14% (placebo) vs 5% (20 μg) vs 4% (40 μg)\n- Relative risk reduction: 65% (20 μg) and 69% (40 μg) for vertebral fractures\n- Nonvertebral fragility fractures: 6% (placebo) vs 3% (both PTH groups) — 53-54% relative risk reduction\n\n**Bone density gains vs placebo:**\n- Lumbar spine: +9 percentage points (20 μg), +13 percentage points (40 μg)\n- Femoral neck: +3 percentage points (20 μg), +6 percentage points (40 μg)\n- Total body bone mineral: +2 to 4 percentage points\n\nThe 40 μg dose increased bone density more but didn't reduce fractures more than 20 μg, and had more side effects. The 40 μg dose also decreased bone density at the radial shaft by 2 percentage points.","whyItMatters":"This is one of the most important trials in osteoporosis history. Before this study, all osteoporosis drugs worked by slowing bone breakdown — parathyroid hormone was the first treatment proven to actually build new bone (an anabolic approach). This trial directly led to the FDA approval of teriparatide (Forteo) in 2002, which became the first bone-building peptide drug and changed how severe osteoporosis is treated.","specificNumbers":"","methodology":"Randomized, placebo-controlled trial of 1,637 postmenopausal women with prior vertebral fractures across multiple countries. Women self-administered daily subcutaneous injections of PTH(1-34) at 20 μg, 40 μg, or placebo. Vertebral radiographs were taken at baseline and study end (median 21 months). Bone mineral density was measured serially by DXA scan. The primary outcome was new vertebral fractures.","limitations":"The trial was stopped early (median 21 months instead of the planned longer duration) due to a concurrent finding that rats given high-dose PTH developed bone tumors (osteosarcoma) — though this has never been observed in humans. The 40 μg dose caused bone loss at the radial shaft, suggesting cortical bone responds differently. Long-term effects beyond 21 months and the question of what happens when treatment stops weren't addressed in this trial."},{"rthcId":"RPEP-00687","title":"The gut and food intake: an update for surgeons.","authors":"Näslund, E; Hellström, P M; Kral, J G","year":2001,"journal":"Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract, 5(5), 556-67","doi":null,"pmid":"11986008","tags":["neuropeptides","weight-loss","gut-healing"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Gut peptides (ghrelin, CCK, GLP-1, PYY) regulate appetite through neural and hormonal pathways that are significantly disrupted by gastrointestinal surgery, requiring surgical awareness for optimal patient management.","whyItMatters":"Appetite problems after GI surgery cause malnutrition, prolonged recovery, and poor outcomes. Understanding the peptide signals involved enables targeted nutritional interventions.","specificNumbers":"","methodology":"Clinical review of gut-brain appetite signaling with emphasis on surgical implications, covering ghrelin, CCK, GLP-1, PYY, and their post-surgical disruption.","limitations":"Review for a surgical audience; limited depth on peptide mechanisms. Post-surgical peptide changes are complex and not fully predictable."},{"rthcId":"RPEP-00688","title":"Restoration of immunocyte functions by thymosin alpha1 in cyclophosphamide-induced immunodeficient mice.","authors":"Ohmori, H; Kamo, M; Yamakoshi, K; Nitta, M H; Hikida, M; Kanayama, N","year":2001,"journal":"Immunopharmacology and immunotoxicology, 23(1), 75-82","doi":null,"pmid":"11322651","tags":["thymosin-alpha-1","immune-function","cancer"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Thymosin alpha-1 restored T-cell proliferation, NK cell cytotoxicity, and Th1 cytokine production (IL-2, IFN-γ) in cyclophosphamide-immunosuppressed mice, demonstrating broad immune reconstitution capacity.","whyItMatters":"Chemotherapy-induced immune suppression increases infection risk and reduces anti-cancer immunity. An agent that quickly restores immune function could reduce complications and improve cancer treatment outcomes.","specificNumbers":"","methodology":"Animal study in cyclophosphamide-immunosuppressed mice. Thymosin alpha-1 administered SC. T-cell proliferation, NK cell activity, and cytokine production measured and compared to immunosuppressed and normal controls.","limitations":"Mouse model with complete immune suppression. Human immune recovery may be slower or different. The optimal timing and dosing for clinical use was not established."},{"rthcId":"RPEP-00689","title":"Stimulation of endorphin neurotransmission in the nucleus accumbens by ethanol, cocaine, and amphetamine.","authors":"Olive, M F; Koenig, H N; Nannini, M A; Hodge, C W","year":2001,"journal":"The Journal of neuroscience : the official journal of the Society for Neuroscience, 21(23), RC184","doi":null,"pmid":"11717387","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00690","title":"Spiro(indoline-3,4'-piperidine) growth hormone secretagogues as ghrelin mimetics.","authors":"Palucki, B L; Feighner, S D; Pong, S; McKee, K K; Hreniuk, D L; Tan, C; Howard, A D; Van der Ploeg, L H; Patchett, A A; Nargund, R P","year":2001,"journal":"Bioorganic & medicinal chemistry letters, 11(14), 1955-7","doi":null,"pmid":"11459669","tags":["ghrp","peptide-design","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Spiro(indoline-piperidine) small molecules mimicking ghrelin's N-terminal active core showed potent GHS-R binding and functional calcium signaling activation, validating small-molecule ghrelin mimicry.","whyItMatters":"Translating a peptide hormone into a stable, oral small molecule drug is one of pharmacology's greatest challenges. These compounds demonstrate it's achievable for ghrelin.","specificNumbers":"","methodology":"In-vitro study. Series of spiro(indoline-piperidine) compounds synthesized and tested in GHS-R binding assays and intracellular calcium flux functional assays.","limitations":"In-vitro data only. Oral bioavailability and in-vivo efficacy not demonstrated for all compounds. Selectivity profile incomplete."},{"rthcId":"RPEP-00691","title":"Chronic cytoprotection: pentadecapeptide BPC 157, ranitidine and propranolol prevent, attenuate and reverse the gastric lesions appearance in chronic alcohol drinking rats.","authors":"Prkacin, I; Aralica, G; Perovic, D; Separovic, J; Gjurasin, M; Lovric-Bencic, M; Stancic-Rokotov, D; Ziger, T; Anic, T; Sikiric, P; Seiwerth, S; Staresinic, M; Mise, S; Rotkvic, I; Jagic, V; Rucman, R; Petek, M; Turkovic, B; Marovic, A; Sjekavica, I; Sebecic, B; Boban-Blagaic, A; Ivasovic, Z","year":2001,"journal":"Journal of physiology, Paris, 95(1-6), 295-301","doi":null,"pmid":"11595453","tags":["bpc-157","gut-healing"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"BPC-157 provided sustained chronic cytoprotection against alcohol-induced gastric lesions, with effectiveness maintained throughout prolonged alcohol exposure alongside liver protection documented in companion study.","whyItMatters":"Chronic drinkers need sustained stomach protection. BPC-157's persistent effectiveness during prolonged alcohol exposure is practically important for real-world alcohol-related gastropathy.","specificNumbers":"","methodology":"Animal study in rats with chronic alcohol administration (3.03 or 7.28 g/kg/day). BPC-157, ranitidine, and propranolol tested for prevention, attenuation, and reversal of chronic gastric lesions.","limitations":"Rat model. Chronic alcohol doses are standardized; human drinking patterns vary. BPC-157 dosing optimization for chronic use not established."},{"rthcId":"RPEP-00692","title":"Portal hypertension and liver lesions in chronically alcohol drinking rats prevented and reversed by stable gastric pentadecapeptide BPC 157 (PL-10, PLD-116), and propranolol, but not ranitidine.","authors":"Prkacin, I; Separovic, J; Aralicia, G; Perovic, D; Gjurasin, M; Lovric-Bencic, M; Stancic-Rokotov, D; Staresinic, M; Anic, T; Mikus, D; Sikiric, P; Seiwerth, S; Mise, S; Rotkvic, I; Jagic, V; Rucman, R; Petek, M; Turkovic, B; Marovic, A; Sebecic, B; Boban-Blagaic, A; Kokic, N","year":2001,"journal":"Journal of physiology, Paris, 95(1-6), 315-24","doi":null,"pmid":"11595456","tags":["bpc-157","liver","gut-healing"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"BPC-157 both prevented (when co-administered) and reversed (when given after damage) chronic alcohol-induced portal hypertension and liver lesions in rats, measured by direct portal vein pressure and histological assessment.","whyItMatters":"Alcoholic liver disease is a leading cause of liver failure and death. A peptide that both prevents AND reverses liver damage could save millions of lives, especially since most liver drugs only slow progression.","specificNumbers":"","methodology":"Animal study in rats. Chronic alcohol administration (7.28 g/kg/day in drinking water). BPC-157 given preventively (with alcohol) or therapeutically (after liver damage established). Portal vein pressure measured directly. Liver histology assessed.","limitations":"Rat alcohol model. The mechanism of hepatoprotection was not determined. Whether BPC-157 can reverse advanced cirrhosis (not just early lesions) is unknown. Human data absent."},{"rthcId":"RPEP-00693","title":"Opioids in chronic pain.","authors":"Przewłocki, R; Przewłocka, B","year":2001,"journal":"European journal of pharmacology, 429(1-3), 79-91","doi":null,"pmid":"11698029","tags":["opioid-peptides","pain"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Endogenous opioid peptides operate through distinct mu, delta, kappa, and NOP receptor systems with unique distribution and function in chronic pain conditions, offering multiple targets for developing targeted, safer analgesics.","whyItMatters":"The opioid crisis demands better pain treatments. Understanding which endogenous opioid pathways are involved in which pain types enables development of targeted analgesics without the addiction risk of non-selective opioids.","specificNumbers":"","methodology":"Comprehensive review covering opioid peptide biogenesis, anatomical distribution, receptor pharmacology, roles in chronic pain states, and therapeutic implications.","limitations":"Comprehensive but written before some recent advances in opioid pharmacogenomics and biased agonism. Not all proposed therapeutic strategies have been clinically validated."},{"rthcId":"RPEP-00694","title":"cDNA and genomic cloning of lacritin, a novel secretion enhancing factor from the human lacrimal gland.","authors":"Sanghi, S; Kumar, R; Lumsden, A; Dickinson, D; Klepeis, V; Trinkaus-Randall, V; Frierson, H F; Laurie, G W","year":2001,"journal":"Journal of molecular biology, 310(1), 127-39","doi":null,"pmid":"11419941","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Lacritin is a newly identified secreted glycoprotein that is highly expressed in human lacrimal gland, moderately in salivary glands, and slightly in thyroid, with no detectable expression in more than 50 other tissues examined.\n\nRecombinant lacritin enhanced unstimulated (constitutive) secretion from lacrimal acinar cells in culture, promoted ductal cell proliferation, and stimulated signaling through tyrosine phosphorylation and calcium release in corneal epithelial cells. It binds several extracellular matrix proteins including collagen IV, laminin-1, and fibronectin. The lacritin gene maps to chromosome 12q13 and consists of five exons with no alternative splicing.","whyItMatters":"Dry eye disease affects hundreds of millions of people worldwide, and current treatments mostly just supplement tears rather than addressing the underlying biology. The discovery of lacritin — a naturally occurring protein that specifically enhances tear production — opens a potential therapeutic avenue for treating dry eye at its source by restoring the gland's own secretory function.","specificNumbers":"","methodology":"The researchers used cDNA and genomic cloning techniques to identify and characterize the lacritin gene. They examined mRNA and protein expression across more than 50 human tissues using in situ hybridization and immunohistochemistry. Functional studies used overnight cultures of rat lacrimal acinar cells to test lacritin's secretion-enhancing effects, and recombinant lacritin was applied to measure its impact on ductal cell proliferation and corneal epithelial cell signaling.","limitations":"This is a discovery and characterization study using cell culture systems and animal tissue, not a clinical trial. The secretion-enhancing effects were demonstrated in overnight cultures of rat acinar cells, which may not fully reflect in vivo human biology. The study establishes lacritin's existence and basic functions but does not test therapeutic applications. The tissue expression survey, while broad, relied on available human tissue samples."},{"rthcId":"RPEP-00695","title":"Generation of dynorphin knockout mice.","authors":"Sharifi, N; Diehl, N; Yaswen, L; Brennan, M B; Hochgeschwender, U","year":2001,"journal":"Brain research. Molecular brain research, 86(1-2), 70-5","doi":null,"pmid":"11165373","tags":["opioid-peptides","pain","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Prodynorphin knockout mice were viable and fertile with altered pain and reward responses, providing a definitive genetic tool for studying dynorphin's specific roles across pain, addiction, mood, and immune function.","whyItMatters":"Genetic knockouts provide definitive evidence for gene function — more precise than pharmacological studies. This model enables the field to determine exactly what dynorphin does throughout the body.","specificNumbers":"","methodology":"Genetic engineering study creating prodynorphin gene knockout mice by homologous recombination. Phenotypic characterization including viability, fertility, pain behavior, and reward paradigms.","limitations":"Knockout mice may develop compensatory mechanisms that mask normal dynorphin functions. Complete gene deletion doesn't model more subtle changes in dynorphin levels seen in disease."},{"rthcId":"RPEP-00696","title":"Anxiolytic effect of BPC-157, a gastric pentadecapeptide: shock probe/burying test and light/dark test.","authors":"Sikiric, P; Jelovac, N; Jelovac-Gjeldum, A; Dodig, G; Staresinic, M; Anic, T; Zoricic, I; Ferovic, D; Aralica, G; Buljat, G; Prkacin, I; Lovric-Bencic, M; Separovic, J; Seiwerth, S; Rucman, R; Petek, M; Turkovic, B; Ziger, T","year":2001,"journal":"Acta pharmacologica Sinica, 22(3), 225-30","doi":null,"pmid":"11742568","tags":["bpc-157","anxiety-mood"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"BPC-157 at 10 μg/kg and 10 ng/kg IP produced anxiolytic effects comparable to diazepam in both the shock probe/burying test (reduced defensive burying) and light/dark test (increased light exploration) in rats.","whyItMatters":"Anxiety disorders affect 300+ million people and current treatments (benzodiazepines) cause dependence. A peptide anxiolytic without benzodiazepine side effects could address a massive unmet need.","specificNumbers":"","methodology":"Animal behavioral study in rats using two validated anxiety models: shock probe/burying test and light/dark test. BPC-157 at two doses compared to diazepam at two doses and saline control.","limitations":"Rat anxiety models are approximations of human anxiety. IP injection route. Long-term anxiolytic efficacy and safety not assessed."},{"rthcId":"RPEP-00697","title":"Cysteamine-colon and cysteamine-duodenum lesions in rats. Attenuation by gastric pentadecapeptide BPC 157, cimetidine, ranitidine, atropine, omeprazole, sulphasalazine and methylprednisolone.","authors":"Sikiric, P; Seiwerth, S; Grabarevic, Z; Balen, I; Aralica, G; Gjurasin, M; Komericki, L; Perovic, D; Ziger, T; Anic, T; Prkacin, I; Separovic, J; Stancic-Rokotov, D; Lovric-Bencic, M; Mikus, D; Staresinic, M; Aralica, J; DiBiaggio, N; Simec, Z; Turkovic, B; Rotkvic, I; Mise, S; Rucman, R; Petek, M; Sebecic, B; Ivasovic, Z; Boban-Blagaic, A; Sjekavica, I","year":2001,"journal":"Journal of physiology, Paris, 95(1-6), 261-70","doi":null,"pmid":"11595448","tags":["bpc-157","gut-healing"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"BPC-157 attenuated cysteamine-induced colon and duodenal lesions, including in gastrectomized rats, demonstrating acid-independent healing and extending its protective effects to the entire gut.","whyItMatters":"Showing BPC-157 heals gut damage without needing acid reduction proves it works through a fundamentally different mechanism from conventional GI drugs — potentially applicable to conditions where acid isn't the problem.","specificNumbers":"","methodology":"Animal study in naive and gastrectomized rats. Cysteamine-induced duodenal and colon lesions treated with BPC-157, cimetidine, ranitidine, omeprazole, sucralfate, and others. Lesion healing compared across acid-present and acid-absent conditions.","limitations":"Rat model. Cysteamine-induced lesions may not perfectly model clinical gut diseases. The specific acid-independent mechanism was not identified."},{"rthcId":"RPEP-00698","title":"1H NMR structural analysis of human ghrelin and its six truncated analogs.","authors":"Silva Elipe, M V; Bednarek, M A; Gao, Y D","year":2001,"journal":"Biopolymers, 59(7), 489-501","doi":null,"pmid":"11745115","tags":["ghrp","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"The octanoyl modification on Ser3 stabilizes a turn structure in ghrelin's N-terminal active core (first 5 residues), explaining its essential role in receptor binding and activation at the structural level.","whyItMatters":"Understanding why ghrelin needs its fatty acid tag at the atomic level enables rational design of drugs that mimic this structure — essential for creating effective oral ghrelin-based therapeutics.","specificNumbers":"","methodology":"NMR structural study determining solution structures of human ghrelin and six N-terminally truncated analogs in membrane-mimetic environments. Structure-activity correlation with known receptor binding data.","limitations":"NMR structures in membrane-mimetic solvent may differ from receptor-bound conformation. Truncated analogs may not fold identically to corresponding regions in full-length ghrelin."},{"rthcId":"RPEP-00699","title":"Growth hormone secretagogue receptor family members and ligands.","authors":"Smith, R G; Leonard, R; Bailey, A R; Palyha, O; Feighner, S; Tan, C; Mckee, K K; Pong, S S; Griffin, P; Howard, A","year":2001,"journal":"Endocrine, 14(1), 9-14","doi":null,"pmid":"11322507","tags":["ghrp","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"The GHS-R family includes the active GHS-R1a (ghrelin receptor, constitutively active) and the orphan GHS-R1b splice variant, with constitutive activity suggesting baseline signaling roles and inverse agonist therapeutic potential.","whyItMatters":"Constitutive activity means the ghrelin receptor signals even when ghrelin isn't present. This has implications for appetite regulation (baseline hunger signaling) and drug development (inverse agonists could reduce this baseline signal for appetite suppression).","specificNumbers":"","methodology":"In-vitro receptor characterization using cloned GHS-R1a and GHS-R1b. Binding, signaling, and constitutive activity assessed in expression systems.","limitations":"In-vitro characterization. GHS-R1b's function remains undetermined. Constitutive activity in expression systems may differ from native tissue."},{"rthcId":"RPEP-00700","title":"Lung lesions and anti-ulcer agents beneficial effect: anti-ulcer agents pentadecapeptide BPC 157, ranitidine, omeprazole and atropine ameliorate lung lesion in rats.","authors":"Stancic-Rokotov, D; Slobodnjak, Z; Aralica, J; Aralica, G; Perovic, D; Staresinic, M; Gjurasin, M; Anic, T; Zoricic, I; Buljat, G; Prkacin, I; Sikiric, P; Seiwerth, S; Rucman, R; Petek, M; Turkovic, B; Kokic, N; Jagic, V; Boban-Blagaic, A","year":2001,"journal":"Journal of physiology, Paris, 95(1-6), 303-8","doi":null,"pmid":"11595454","tags":["bpc-157","respiratory","gut-healing"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"BPC-157 attenuated both intratracheal HCl-induced lung lesions and associated gastric damage in rats, demonstrating cytoprotective effects extending beyond the GI tract to the respiratory system.","whyItMatters":"Acid aspiration lung injury has no specific treatment. A peptide that protects both lungs and stomach from acid damage could benefit patients at risk of aspiration, including surgical patients and those with GERD.","specificNumbers":"","methodology":"Animal study in rats. Intratracheal HCl instillation to induce lung and secondary gastric lesions. BPC-157, ranitidine, omeprazole, and other anti-ulcer agents tested for both lung and gastric protection.","limitations":"Rat model with acute chemical lung injury. The mechanism of lung protection was not determined. Whether BPC-157 protects against other types of lung injury is unknown."},{"rthcId":"RPEP-00701","title":"Interactions of growth hormone secretagogues and growth hormone-releasing hormone/somatostatin.","authors":"Tannenbaum, G S; Bowers, C Y","year":2001,"journal":"Endocrine, 14(1), 21-7","doi":null,"pmid":"11322498","tags":["ghrp","hormone-optimization","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"GH secretagogues simultaneously activate GHRH neurons and suppress somatostatin neurons in the hypothalamus, creating a dual accelerator-plus-brake-release mechanism for amplified GH secretion.","whyItMatters":"Understanding this dual mechanism explains GH secretagogue potency and informs strategies for optimizing their clinical effects. It also explains why they synergize with exogenous GHRH.","specificNumbers":"","methodology":"Animal studies using Fos immunohistochemistry, in situ hybridization, and electrophysiology to map GH secretagogue effects on GHRH and somatostatin neurons in the hypothalamus.","limitations":"Animal studies with indirect measures of neuronal activity. The specific intracellular pathways mediating GHRH activation and somatostatin suppression were not fully characterized."},{"rthcId":"RPEP-00702","title":"Relationship between plasma levels of cardiac natriuretic peptides and soluble Fas: plasma soluble Fas as a prognostic predictor in patients with congestive heart failure.","authors":"Tsutamoto, T; Wada, A; Maeda, K; Mabuchi, N; Hayashi, M; Tsutsui, T; Ohnishi, M; Fujii, M; Matsumoto, T; Yamamoto, T; Takayama, T; Kinoshita, M","year":2001,"journal":"Journal of cardiac failure, 7(4), 322-8","doi":null,"pmid":"11782855","tags":["natriuretic-peptides","cardiovascular","inflammation"],"studyType":"cross-sectional","evidenceStrength":"moderate","keyFinding":"Plasma BNP correlated with soluble Fas (apoptosis marker) in CHF patients, and sFas independently predicted prognosis, establishing a link between natriuretic peptide signaling and cardiac programmed cell death.","whyItMatters":"Heart failure involves both mechanical dysfunction and cell death. Combining peptide biomarkers (BNP) with apoptosis markers (sFas) could provide a more complete picture of disease severity and trajectory.","specificNumbers":"","methodology":"Cross-sectional study measuring BNP, ANP, N-terminal ANP, soluble Fas, and TNF-alpha in congestive heart failure patients. Correlations and prognostic analysis performed.","limitations":"Cross-sectional design; causation uncertain. The mechanistic link between BNP and sFas is correlational. Specific sFas cutoffs for clinical use not established."},{"rthcId":"RPEP-00703","title":"The neuroendocrine response to stress is a dynamic process.","authors":"Van den Berghe, G","year":2001,"journal":"Best practice & research. Clinical endocrinology & metabolism, 15(4), 405-19","doi":null,"pmid":"11800514","tags":["ghrp","hormone-optimization"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"The neuroendocrine response to critical illness is biphasic (acute activation → chronic suppression), and therapeutic intervention must be phase-appropriate: GH secretagogues/TRH benefit the chronic phase but acute-phase augmentation may be harmful.","whyItMatters":"Timing is everything in ICU endocrine therapy. This review explains why the same therapy (GH augmentation) can save lives in chronic illness but kill patients in acute illness.","specificNumbers":"","methodology":"Clinical review integrating neuroendocrine profiling data from critically ill patients with clinical trial outcomes, including the negative GH replacement trial and positive GH secretagogue studies.","limitations":"Review based on available clinical data through 2001. Optimal timing of GH secretagogue therapy not precisely defined."},{"rthcId":"RPEP-00704","title":"Interactive regulation of postmenopausal growth hormone insulin-like growth factor axis by estrogen and growth hormone-releasing peptide-2.","authors":"Veldhuis, J D; Evans, W S; Bowers, C Y; Anderson, S","year":2001,"journal":"Endocrine, 14(1), 45-62","doi":null,"pmid":"11322501","tags":["ghrp","hormone-optimization","fertility"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Estrogen is the proximate sex steroid sustaining GH secretion across the human lifespan, modulating GHRP sensitivity, somatostatin withdrawal, and GH feedback through specific neuroendocrine mechanisms that decline with menopause.","whyItMatters":"Menopause-related GH decline contributes to muscle loss, fat gain, and bone weakening. Understanding estrogen's role enables combined estrogen-GH secretagogue therapy strategies.","specificNumbers":"","methodology":"Review of clinical and physiological data on estrogen-GH axis interactions, incorporating GHRP-2 stimulation studies in pre- and postmenopausal women.","limitations":"Review synthesizing limited clinical data on estrogen-GHRP interactions. Optimal combination therapy protocols not established."},{"rthcId":"RPEP-00705","title":"Ghrelin enhances appetite and increases food intake in humans.","authors":"Wren, A M; Seal, L J; Cohen, M A; Brynes, A E; Frost, G S; Murphy, K G; Dhillo, W S; Ghatei, M A; Bloom, S R","year":2001,"journal":"The Journal of clinical endocrinology and metabolism, 86(12), 5992","doi":null,"pmid":"11739476","tags":["ghrp","weight-loss","clinical-trials"],"studyType":"RCT","evidenceStrength":"strong","keyFinding":"IV ghrelin infusion in healthy humans increased subjective appetite ratings and food intake significantly, alongside GH stimulation, providing the first proof that ghrelin is a human hunger hormone.","whyItMatters":"Confirming ghrelin drives human appetite transformed it from an interesting lab finding to a validated drug target. It justified developing ghrelin-based drugs for cachexia, anorexia, and potentially obesity (via antagonists).","specificNumbers":"","methodology":"Randomized, placebo-controlled study in healthy volunteers. IV ghrelin infusion with subjective appetite visual analog scale ratings and ad libitum buffet food intake measurement. GH measured.","limitations":"Healthy volunteers; responses in patients with appetite disorders may differ. IV administration may not predict responses to long-acting formulations. Acute study doesn't predict chronic appetite effects."},{"rthcId":"RPEP-00706","title":"Antisera against endogenous opioids increase the nocifensive response to formalin: demonstration of inhibitory beta-endorphinergic control.","authors":"Wu, H; Hung, K; Ohsawa, M; Mizoguchi, H; Tseng, L F","year":2001,"journal":"European journal of pharmacology, 421(1), 39-43","doi":null,"pmid":"11408047","tags":["opioid-peptides","pain"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"ICV anti-beta-endorphin increased acute phase formalin pain, anti-leu-enkephalin increased late inflammatory phase pain, and anti-dynorphin affected both phases, demonstrating peptide-specific roles in endogenous pain modulation.","whyItMatters":"Knowing which opioid peptide naturally controls which type of pain enables targeted analgesic development — different drugs for acute versus inflammatory pain.","specificNumbers":"","methodology":"Animal study in mice using ICV injection of antisera against beta-endorphin, leu-enkephalin, met-enkephalin, or dynorphin A before formalin testing. Early (acute) and late (inflammatory) pain phases measured separately.","limitations":"Mouse formalin test. ICV antibody approach has limitations (incomplete blocking, specificity concerns). Acute test may not predict chronic pain roles."},{"rthcId":"RPEP-00707","title":"The small intestine is an important source of adrenomedullin release during polymicrobial sepsis.","authors":"Zhou, M; Chaudry, I H; Wang, P","year":2001,"journal":"American journal of physiology. Regulatory, integrative and comparative physiology, 281(2), R654-60","doi":null,"pmid":"11448871","tags":["neuropeptides","inflammation","gut-healing"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Small intestinal ADM mRNA and protein were significantly upregulated during polymicrobial sepsis, with the gut releasing ADM into portal circulation, establishing the intestine as a major source of circulating ADM during sepsis.","whyItMatters":"The gut is the body's largest interface with bacteria. Its massive ADM production during sepsis could be a response to intestinal bacterial translocation — connecting gut barrier failure to systemic cardiovascular dysfunction.","specificNumbers":"","methodology":"Animal study in rat sepsis model. ADM mRNA (RT-PCR) and protein (immunohistochemistry, RIA) measured in small intestinal tissue. Portal vein ADM levels assessed for gut contribution to circulating ADM.","limitations":"Rat sepsis model. The relative contribution of gut versus cardiovascular ADM to total circulating levels was not precisely quantified."},{"rthcId":"RPEP-00708","title":"The inhibitory effect of Selank on enkephalin-degrading enzymes as a possible mechanism of its anxiolytic activity.","authors":"Zozulya, A A; Kost, N V; Yu Sokolov, O; Gabaeva, M V; Grivennikov, I A; Andreeva, L N; Zolotarev, Y A; Ivanov, S V; Andryushchenko, A V; Myasoedov, N F; Smulevich, A B","year":2001,"journal":"Bulletin of experimental biology and medicine, 131(4), 315-7","doi":null,"pmid":"11550013","tags":["selank","anxiety-mood","opioid-peptides"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"Anxiety patients showed accelerated enkephalin degradation, and Selank's anxiolytic effect correlated with inhibition of enkephalin-degrading enzymes, preserving endogenous opioid-mediated anxiety relief.","whyItMatters":"Most anxiolytics work through GABA (benzodiazepines) or serotonin (SSRIs). Selank's opioid-preserving mechanism represents a fundamentally different approach — boosting natural anxiety control rather than artificially suppressing anxiety circuits.","specificNumbers":"","methodology":"Clinical study examining enkephalin half-life and enkephalinase activity in blood from patients with various anxiety and phobic disorders (DSM-4 criteria). Selank treatment effects on both anxiety symptoms and enkephalin metabolism measured.","limitations":"Clinical study with limited methodological details in abstract. The correlation between enzyme inhibition and symptom improvement doesn't prove causation. Blood enkephalin dynamics may not reflect brain levels."},{"rthcId":"RPEP-00709","title":"Morgan 2002 Npy Cortisol Military Stress","authors":"","year":2002,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00710","title":"Role of defensins in inflammatory lung disease.","authors":"Aarbiou, Jamil; Rabe, Klaus F; Hiemstra, Pieter S","year":2002,"journal":"Annals of medicine, 34(2), 96-101","doi":null,"pmid":"12108580","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00711","title":"Ghrelin and synthetic GH secretagogues.","authors":"Arvat, Emanuela; Broglio, Fabio; Aimaretti, Gianluca; Benso, Andrea; Giordano, Roberta; Deghenghi, Romano; Ghigo, Ezio","year":2002,"journal":"Best practice & research. Clinical endocrinology & metabolism, 16(3), 505-17","doi":null,"pmid":"12464231","tags":["ghrp","hormone-optimization","weight-loss","clinical-trials"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"The ghrelin-GHS system is a multi-functional endocrine network with validated roles in GH regulation, appetite control, adiposity, and cardiovascular function, with therapeutic implications across multiple medical specialties.","whyItMatters":"Presenting the unified ghrelin-GHS system helps clinicians understand why GH secretagogues affect appetite, body composition, and heart function — not just GH levels.","specificNumbers":"","methodology":"Review synthesizing ghrelin biology with synthetic GH secretagogue pharmacology and clinical data.","limitations":"Review from 2002; some ghrelin functions were still being characterized. Long-term therapeutic implications were still speculative."},{"rthcId":"RPEP-00712","title":"Ghrelin and des-acyl ghrelin inhibit cell death in cardiomyocytes and endothelial cells through ERK1/2 and PI 3-kinase/AKT.","authors":"Baldanzi, Gianluca; Filigheddu, Nicoletta; Cutrupi, Santina; Catapano, Filomena; Bonissoni, Sara; Fubini, Alberto; Malan, Daniela; Baj, Germano; Granata, Riccarda; Broglio, Fabio; Papotti, Mauro; Surico, Nicola; Bussolino, Federico; Isgaard, Jorgen; Deghenghi, Romano; Sinigaglia, Fabiola; Prat, Maria; Muccioli, Giampiero; Ghigo, Ezio; Graziani, Andrea","year":2002,"journal":"The Journal of cell biology, 159(6), 1029-37","doi":null,"pmid":"12486113","tags":["ghrp","cardiovascular","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Both acylated ghrelin and des-acyl ghrelin inhibited apoptosis in cardiomyocytes and endothelial cells via ERK1/2 and PI3K/Akt pathways, with des-acyl ghrelin's activity demonstrating GHS-R-independent cardiovascular protection.","whyItMatters":"Des-acyl ghrelin is the most abundant form in blood. If it protects the heart independently of the GHS receptor, it represents a major, previously unrecognized cardiovascular protective system with its own unknown receptor.","specificNumbers":"","methodology":"In-vitro study. Cultured cardiomyocytes and endothelial cells exposed to serum starvation or doxorubicin to induce apoptosis. Both ghrelin forms tested for survival signaling (ERK1/2, PI3K/Akt) and apoptosis inhibition.","limitations":"In-vitro cell culture study. The des-acyl ghrelin receptor has not been identified. In-vivo cardioprotective significance not established."},{"rthcId":"RPEP-00713","title":"Characterization of the anti-HIV effects of native lactoferrin and other milk proteins and protein-derived peptides.","authors":"Berkhout, Ben; van Wamel, Jeroen L B; Beljaars, Leonie; Meijer, Dirk K F; Visser, Servaas; Floris, René","year":2002,"journal":"Antiviral research, 55(2), 341-55","doi":null,"pmid":"12103434","tags":["antimicrobial-peptides","infection"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Native bovine lactoferrin and derived peptides (lactoferricin) inhibited HIV entry into cells, with positively charged proteins/peptides showing the strongest activity, supporting milk-derived compounds as natural antivirals.","whyItMatters":"HIV prevention remains a global priority. Natural milk-derived antivirals that block virus entry could complement existing prevention strategies, particularly in resource-limited settings where milk products are accessible.","specificNumbers":"","methodology":"In-vitro antiviral screening of purified bovine milk proteins and peptide fragments against HIV-1 entry using cell-based infection assays.","limitations":"In-vitro activity. Concentrations required for HIV inhibition may not be achievable through dietary consumption. Clinical anti-HIV efficacy not demonstrated."},{"rthcId":"RPEP-00714","title":"Regulation of renal tubular sodium transport by cardiac natriuretic peptides: two decades of research.","authors":"Bełtowski, Jerzy; Wójcicka, Grazyna","year":2002,"journal":"Medical science monitor : international medical journal of experimental and clinical research, 8(2), RA39-52","doi":null,"pmid":"11859295","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00715","title":"Thymosin alpha1. SciClone Pharmaceuticals.","authors":"Billich, Andreas","year":2002,"journal":"Current opinion in investigational drugs (London, England : 2000), 3(5), 698-707","doi":null,"pmid":"12090542","tags":["thymosin-alpha-1","immune-function","infection","cancer","clinical-trials"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Thymosin alpha-1 demonstrates clinical efficacy across hepatitis B, hepatitis C (with IFN), cancer (with chemo), and potentially HIV, with excellent tolerability and a favorable safety profile across all studied indications.","whyItMatters":"This is the definitive clinical reference for thymosin alpha-1, covering everything a prescriber or researcher needs to know about this peptide drug's established and emerging clinical applications.","specificNumbers":"","methodology":"Comprehensive pharmaceutical review covering pharmacology, pharmacokinetics, all clinical trial data (Phase I-III), adverse effects, and dosing across multiple indications.","limitations":"Detailed 2002 review. Some indications had limited trial sizes. Hepatitis C treatment has since been revolutionized by DAAs. Some clinical comparisons were not placebo-controlled."},{"rthcId":"RPEP-00716","title":"A synthetic hexapeptide (Argireline) with antiwrinkle activity.","authors":"Blanes-Mira, C; Clemente, J; Jodas, G; Gil, A; Fernández-Ballester, G; Ponsati, B; Gutierrez, L; Pérez-Payá, E; Ferrer-Montiel, A","year":2002,"journal":"International journal of cosmetic science, 24(5), 303-10","doi":"10.1046/j.1467-2494.2002.00153.x","pmid":"18498523","tags":["cosmetic-peptides"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"Argireline (Ac-EEMQRR-NH₂), a synthetic six-amino-acid peptide, reduced wrinkle depth by up to 30% in healthy women volunteers after 30 days of topical application at 10% concentration in an oil-in-water emulsion.\n\nThe peptide works by mimicking botulinum toxin's mechanism: it inhibits neurotransmitter release by interfering with the SNARE complex — the protein machinery that cells use to release chemical signals at nerve endings. While Argireline's inhibitory potency was similar to botulinum toxin type A, its overall efficacy was lower, as expected for a topical peptide versus an injected neurotoxin.\n\nCritically, Argireline showed no oral toxicity in vivo and caused no primary skin irritation even at high doses, establishing it as a non-toxic alternative to botulinum toxin injections for cosmetic wrinkle reduction.","whyItMatters":"This is the foundational study for one of the most commercially successful cosmetic peptides ever developed. Argireline offered something the market desperately wanted: a Botox-like wrinkle reduction effect that could be applied as a cream rather than injected. While less effective than actual botulinum toxin, the trade-off — no needles, no toxicity risk, available over-the-counter — made it revolutionary for the skincare industry and launched the entire category of 'neurotransmitter-inhibiting' cosmetic peptides.","specificNumbers":"Up to 30% wrinkle depth reduction · 30 days treatment · 10% concentration in O/W emulsion · Potency similar to BoNT A · No oral toxicity or primary irritation","methodology":"The researchers used rational peptide design to create Argireline based on the known mechanism of botulinum toxin. The peptide was tested in a human volunteer study where healthy women applied a 10% Argireline emulsion topically for 30 days, with wrinkle depth measured using skin topography analysis. Separately, the mechanism of action was studied in cell-based assays measuring neurotransmitter release and SNARE complex formation. Safety was assessed through in vivo oral toxicity testing and primary skin irritation tests.","limitations":"The abstract does not specify the number of volunteers or whether the study was blinded, placebo-controlled, or randomized — key methodological details. The 'up to 30%' wrinkle reduction language suggests this was the best result, not the average, which could overstate typical effects. The study was conducted by researchers who appear to be involved in the peptide's development, creating a potential conflict of interest. Long-term effects beyond 30 days were not assessed."},{"rthcId":"RPEP-00717","title":"Ghrelin: endocrine and non-endocrine actions.","authors":"Broglio, Fabio; Arvat, Emanuela; Benso, Andrea; Papotti, Mauro; Muccioli, Giampiero; Deghenghi, Romano; Ghigo, Ezio","year":2002,"journal":"Journal of pediatric endocrinology & metabolism : JPEM, 15 Suppl 5, 1219-27","doi":null,"pmid":"12510973","tags":["ghrp","hormone-optimization","weight-loss","cardiovascular"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Ghrelin displays endocrine (GH release) and non-endocrine (appetite stimulation, adipogenesis, cardioprotection) activities, with cardiovascular protection mediated by both acyl and des-acyl forms — a multi-system metabolic hormone.","whyItMatters":"Clinical use of GH secretagogues must account for ghrelin's diverse effects. The cardiovascular protection from even des-acyl ghrelin opens unexpected therapeutic opportunities.","specificNumbers":"","methodology":"Review of ghrelin biology covering GH-releasing, orexigenic, adipogenic, and cardiovascular protective effects in animal and human studies.","limitations":"Review from 2002 when some ghrelin functions were still being characterized. Therapeutic applications were largely conceptual."},{"rthcId":"RPEP-00718","title":"Ghrelin: much more than a natural growth hormone secretagogue.","authors":"Broglio, Fabio; Arvat, Emanuela; Benso, Andrea; Gottero, Cristina; Prodam, Flavia; Granata, Riccarda; Papotti, Mauro; Muccioli, Giampiero; Deghenghi, Romano; Ghigo, Ezio","year":2002,"journal":"The Israel Medical Association journal : IMAJ, 4(8), 607-13","doi":null,"pmid":"12183865","tags":["ghrp","hormone-optimization","weight-loss","cardiovascular"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Ghrelin acts as a multi-system metabolic regulator beyond GH release, with validated roles in appetite, energy balance, gastric motility, pancreatic function, cardiovascular regulation, and immune modulation through widely distributed receptors.","whyItMatters":"Drug developers targeting ghrelin must account for its multi-system effects. What appears as a side effect in one application may be the primary benefit in another.","specificNumbers":"","methodology":"Comprehensive review of ghrelin biology covering tissue expression, receptor distribution, and functional effects across endocrine, metabolic, gastrointestinal, cardiovascular, and immune systems.","limitations":"Review from 2002 when many ghrelin functions were newly described. Some proposed functions needed further validation."},{"rthcId":"RPEP-00719","title":"Pathophysiological and clinical relevance of circulating levels of cardiac natriuretic hormones: are they merely markers of cardiac disease?","authors":"Clerico, Aldo","year":2002,"journal":"Clinical chemistry and laboratory medicine, 40(8), 752-60","doi":null,"pmid":"12392299","tags":["natriuretic-peptides","cardiovascular","clinical-trials"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Natriuretic peptides serve dual roles as sensitive cardiac biomarkers AND active cardiovascular protectors, with evidence supporting both diagnostic utility and therapeutic potential through their vasodilatory, natriuretic, and neurohormonal-suppressive actions.","whyItMatters":"Understanding that natriuretic peptides are active protectors (not just markers) justifies therapies that boost them — the scientific basis for sacubitril/valsartan (Entresto).","specificNumbers":"","methodology":"Review synthesizing diagnostic/prognostic biomarker data with physiological/therapeutic evidence for natriuretic peptide cardiovascular effects.","limitations":"The relative therapeutic contribution of boosted natriuretic peptides versus reduced angiotensin is still debated for drugs like Entresto."},{"rthcId":"RPEP-00720","title":"The role of defensins in lung biology and therapy.","authors":"Cole, Alexander M; Waring, Alan J","year":2002,"journal":"American journal of respiratory medicine : drugs, devices, and other interventions, 1(4), 249-59","doi":null,"pmid":"14720045","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review established several key findings about defensins in lung biology:\n\n• Humans produce at least 10 defensin molecules — 6 alpha-defensins and 4 beta-defensins — that are structurally and functionally similar\n• Defensins kill a broad spectrum of microorganisms while permitting little resistance development\n• Many defensin peptides can neutralize lipopolysaccharide (LPS) effects on macrophages and reduce proinflammatory cytokine release, providing protection against septic shock\n• Protegrin-1 (a pig-derived minidefensin) served as a template for iseganan, which was in phase III clinical trials for oral mucositis from chemotherapy\n• Prospective uses included respiratory pathogen control in cystic fibrosis and prevention of ventilator-associated pneumonia\n• Major technical hurdle: synthesizing large quantities of complexly folded defensin peptides at scale","whyItMatters":"The lungs are the body's most exposed internal organ, constantly fighting airborne pathogens. Understanding how defensins protect the airways is fundamental to treating lung infections, especially in vulnerable populations like cystic fibrosis patients and ventilated ICU patients. The fact that defensin-based drugs had already reached phase III trials by 2002 demonstrated the practical potential of translating innate immunity research into medicine.","specificNumbers":"","methodology":"This was a narrative review examining published literature on defensins and related antimicrobial peptides in lung biology. The review covered the innate immune defense system of the airways, the structure and function of defensin molecules, their antimicrobial mechanisms, and the development of defensin-based therapeutics including clinical trial progress.","limitations":"Published in 2002, this review predates significant advances in defensin research and the clinical outcomes of iseganan trials. The review is narrative rather than systematic. At the time, direct evidence for defensins' central roles in host defense had only recently become available, so some claims were based on in vitro and animal data. The technical challenges of large-scale peptide synthesis described remain partially unresolved today."},{"rthcId":"RPEP-00721","title":"The cyclotides: novel macrocyclic peptides as scaffolds in drug design.","authors":"Craik, David J; Simonsen, Shane; Daly, Norelle L","year":2002,"journal":"Current opinion in drug discovery & development, 5(2), 251-60","doi":null,"pmid":"11926131","tags":["cyclic-peptides","peptide-design","peptide-delivery"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Cyclotides combine exceptional structural stability (thermal, enzymatic, chemical resistance) with sequence-tolerant scaffolding capability, enabling design of stable peptide drugs through grafting bioactive sequences into the cyclotide framework.","whyItMatters":"Most peptide drugs fail because they're unstable in the body. Cyclotides solve this stability problem while maintaining the ability to present drug-like sequences, potentially enabling oral peptide drugs.","specificNumbers":"","methodology":"Review of cyclotide discovery, structural biology, stability properties, known bioactivities, and drug design applications including grafting strategies.","limitations":"Drug design with cyclotides was still in early stages. Not all bioactive sequences can be successfully grafted. Manufacturing at pharmaceutical scale is challenging."},{"rthcId":"RPEP-00722","title":"Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery.","authors":"Cummings, David E; Weigle, David S; Frayo, R Scott; Breen, Patricia A; Ma, Marina K; Dellinger, E Patchen; Purnell, Jonathan Q","year":2002,"journal":"The New England journal of medicine, 346(21), 1623-30","doi":null,"pmid":"12023994","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00723","title":"The CRF peptide family and their receptors: yet more partners discovered.","authors":"Dautzenberg, Frank M; Hauger, Richard L","year":2002,"journal":"Trends in pharmacological sciences, 23(2), 71-7","doi":null,"pmid":"11830263","tags":["neuropeptides","anxiety-mood","inflammation"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Expanded CRF peptide family including urocortins reveals distinct CRF1 (anxiety/depression) and CRF2 (stress coping/appetite/cardiovascular) receptor functions, enabling receptor-specific drug development.","whyItMatters":"Most psychiatric stress research focused on CRF1. The CRF2 receptor's distinct role in stress coping and appetite opens entirely new therapeutic avenues for eating disorders and cardiovascular stress responses.","specificNumbers":"","methodology":"Review of newly discovered CRF-related peptides, receptor characterization, and their roles in stress, anxiety, eating, cardiac, and inflammatory disorders.","limitations":"Brief review. Clinical validation of CRF receptor-selective drugs was still limited. Some proposed receptor functions were based on animal data."},{"rthcId":"RPEP-00724","title":"Plasma levels and cardiovascular gene expression of urotensin-II in human heart failure.","authors":"Dschietzig, Thomas; Bartsch, Cornelia; Pregla, Rainer; Zurbrügg, Heinz Robert; Armbruster, Franz Paul; Richter, Christoph; Laule, Michael; Romeyke, Elfrun; Neubert, Charlotte; Voelter, Wolfgang; Baumann, Gert; Stangl, Karl","year":2002,"journal":"Regulatory peptides, 110(1), 33-8","doi":null,"pmid":"12468107","tags":["cardiovascular","biomarkers"],"studyType":"clinical-observational","evidenceStrength":"moderate","keyFinding":"Urotensin-II plasma levels and its gene expression in heart and blood vessels were unchanged in patients with congestive heart failure compared to healthy controls. The peptide levels did not differ across measurement sites (pulmonary artery, left ventricle, coronary sinus, or arm vein), and even when severe heart failure patients received vasodilator therapy that significantly improved their hemodynamics (cardiac index up 78%, wedge pressure down 55%), urotensin-II levels stayed flat over 24 hours.\n\nGene expression of the urotensin-II precursor in heart tissue and blood vessels was also no different between end-stage heart failure patients and controls with normal heart function.","whyItMatters":"Urotensin-II had been identified as the most potent vasoconstrictor known, which made it a prime suspect in heart failure — a condition where blood vessels constrict too much and the heart can't keep up. This study provided early evidence that despite its powerful vasoconstrictor ability, urotensin-II doesn't appear to play a major role in human heart failure, redirecting research efforts toward other peptide targets.","specificNumbers":"n=34 · Controls CI 3.5 l/min/m² · Severe CHF CI 1.8 l/min/m² · Vasodilator therapy: CI +78%, PCWP -55% · No change in U-II over 24h","methodology":"Researchers compared three groups: 13 healthy controls, 10 patients with moderate heart failure, and 11 with severe heart failure. They measured urotensin-II levels in blood drawn from four different locations in the cardiovascular system. They also checked gene expression of the urotensin-II precursor in heart tissue and blood vessels using RT-PCR. In severe heart failure patients who received vasodilator therapy, they tracked urotensin-II levels over 24 hours.","limitations":"Small sample size (34 total participants). Single-center study. Only measured circulating levels and gene expression — did not assess receptor expression or local tissue activity. The 24-hour monitoring window may have been too short to capture slower changes."},{"rthcId":"RPEP-00725","title":"Evidence for a direct antitumor mechanism of action of bovine lactoferricin.","authors":"Eliassen, Liv Tone; Berge, Gerd; Sveinbjørnsson, Baldur; Svendsen, John S; Vorland, Lars H; Rekdal, Øystein","year":2002,"journal":"Anticancer research, 22(5), 2703-10","doi":null,"pmid":"12529985","tags":["antimicrobial-peptides","cancer"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Bovine lactoferricin inhibited tumor growth in immunodeficient mice, proving a direct cytotoxic antitumor mechanism independent of immune system activation, likely through cancer cell membrane disruption.","whyItMatters":"A natural peptide that directly kills cancer cells without requiring an immune system could work even in immunocompromised cancer patients — a population where immunotherapy-based approaches fail.","specificNumbers":"","methodology":"Animal study using immunodeficient mice (lacking functional immune systems) to distinguish direct antitumor from immune-mediated effects. LfcinB treatment of tumor-bearing mice with tumor growth measurement.","limitations":"Specific tumor types tested may not represent all cancers. The exact membrane disruption mechanism in cancer cells needs further characterization. Dosing and delivery for clinical use not established."},{"rthcId":"RPEP-00726","title":"Adrenomedullin has multiple roles in disease stress: development and remission of the inflammatory response.","authors":"Elsasser, Ted H; Kahl, Stas","year":2002,"journal":"Microscopy research and technique, 57(2), 120-9","doi":null,"pmid":"11921363","tags":["neuropeptides","inflammation"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Adrenomedullin acts as both a pro-inflammatory stress responder and an anti-inflammatory tissue protector during disease, with its dual nature and temporal dynamics determining whether it helps or harms at each stage.","whyItMatters":"ADM's dual nature means simple antagonism or augmentation could backfire. Therapy must be timed and targeted to the specific phase and aspect of ADM's function — a precision medicine challenge.","specificNumbers":"","methodology":"Comprehensive review of adrenomedullin in trauma, infection, and sepsis, covering gene regulation, tissue expression, systemic effects, and interaction with inflammatory mediators.","limitations":"Review synthesizing complex and sometimes contradictory data. The optimal therapeutic strategy for ADM modulation was not clearly defined."},{"rthcId":"RPEP-00727","title":"Growth hormone secretagogues: past, present and future.","authors":"Fehrentz, Jean-Alain; Martinez, Jean; Boeglin, Damien; Guerlavais, Vincent; Deghenghi, Romano","year":2002,"journal":"IDrugs : the investigational drugs journal, 5(8), 804-14","doi":null,"pmid":"12802697","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00728","title":"beta-Endorphin modulation of pressor response to hyperventilation in hypertensive patients.","authors":"Fontana, Fiorella; Bernardi, Pasquale; Spampinato, Santi; Toro, Rosanna Di; Bugiardini, Raffaele","year":2002,"journal":"Peptides, 23(5), 911-8","doi":null,"pmid":"12084522","tags":["opioid-peptides","cardiovascular"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"Beta-endorphin levels predicted blood pressure response to hyperventilation in hypertensives: high endorphin = BP decrease; low endorphin with high norepinephrine/dynorphin = BP increase — opioids modulate cardiovascular stress response.","whyItMatters":"Individual variation in cardiovascular stress responses may be explained by opioid peptide profiles. This could enable prediction of dangerous stress-induced blood pressure spikes in hypertensive patients.","specificNumbers":"","methodology":"Clinical study in 31 hypertensive patients. Blood pressure, beta-endorphin, dynorphin B, and norepinephrine measured before and after hyperventilation. Patients grouped by BP response pattern.","limitations":"31 patients — small for subgroup analysis. Single stress paradigm (hyperventilation). Cross-sectional measurement at one timepoint."},{"rthcId":"RPEP-00729","title":"The antiproliferative effect of synthetic peptidyl GH secretagogues in human CALU-1 lung carcinoma cells.","authors":"Ghè, Corrado; Cassoni, Paola; Catapano, Filomena; Marrocco, Tiziana; Deghenghi, Romano; Ghigo, Ezio; Muccioli, Giampiero; Papotti, Mauro","year":2002,"journal":"Endocrinology, 143(2), 484-91","doi":null,"pmid":"11796502","tags":["ghrp","cancer","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Synthetic peptidyl GH secretagogues inhibited proliferation of human CALU-1 lung carcinoma cells that express high levels of GHS receptors, demonstrating antiproliferative rather than growth-promoting activity in this cancer type.","whyItMatters":"The cancer biology community worried GH secretagogues might promote cancer growth. This study shows the opposite in lung cancer cells — they actually inhibit growth — which could change the safety assessment.","specificNumbers":"","methodology":"In-vitro study. GHS receptor binding characterized in human lung cancer tissues. CALU-1 lung cancer cell proliferation measured after treatment with hexarelin and other GH secretagogues.","limitations":"Single cancer cell line. In-vitro proliferation inhibition may not translate to in-vivo tumor suppression. The mechanism of growth inhibition was not determined."},{"rthcId":"RPEP-00730","title":"Beta-strand mimicking macrocyclic amino acids: templates for protease inhibitors with antiviral activity.","authors":"Glenn, Matthew P; Pattenden, Leonard K; Reid, Robert C; Tyssen, David P; Tyndall, Joel D A; Birch, Christopher J; Fairlie, David P","year":2002,"journal":"Journal of medicinal chemistry, 45(2), 371-81","doi":null,"pmid":"11784141","tags":["cyclic-peptides","infection"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Novel macrocyclic amino acids that constrain peptides into beta-strand conformations were developed as protease inhibitor templates, showing application in antiviral drug design against HIV and HCV proteases.","whyItMatters":"Converting flexible peptides into rigid macrocyclic drugs improves their potency, selectivity, and oral bioavailability — key challenges in antiviral peptide drug development.","specificNumbers":"","methodology":"In-vitro medicinal chemistry study. Macrocyclic amino acids designed, synthesized, and incorporated into protease inhibitor scaffolds. Tested against viral proteases.","limitations":"In-vitro design and testing. In-vivo pharmacology not demonstrated. The specific potency against viral proteases was not detailed."},{"rthcId":"RPEP-00731","title":"The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans.","authors":"Gnanapavan, Sharmilee; Kola, Blerina; Bustin, Stephen A; Morris, Damian G; McGee, Patrick; Fairclough, Peter; Bhattacharya, Satya; Carpenter, Robert; Grossman, Ashley B; Korbonits, Márta","year":2002,"journal":"The Journal of clinical endocrinology and metabolism, 87(6), 2988","doi":null,"pmid":"12050285","tags":["ghrp","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Ghrelin mRNA was detected in stomach (highest), intestine, pancreas, kidney, and other tissues, while GHS-R1a and GHS-R1b showed distinct but overlapping tissue distributions across virtually all major human organs.","whyItMatters":"The widespread tissue expression explains why ghrelin affects so many body systems. For drug development, it means GH secretagogues will have multi-organ effects that must be anticipated and managed.","specificNumbers":"","methodology":"In-vitro tissue distribution study using RT-PCR to detect ghrelin, GHS-R1a, and GHS-R1b mRNA expression across a panel of human tissues and cell types.","limitations":"mRNA detection doesn't prove functional protein expression. RT-PCR can detect low-level expression that may not be physiologically relevant. Human tissue availability limits sample sizes."},{"rthcId":"RPEP-00732","title":"Natriuretic peptides in relation to the cardiac innervation and conduction system.","authors":"Hansson, Magnus","year":2002,"journal":"Microscopy research and technique, 58(5), 378-86","doi":null,"pmid":"12226807","tags":["natriuretic-peptides","cardiovascular"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"ANP, BNP, and CNP are expressed in the cardiac conduction system (SA node, AV node, His bundle, Purkinje fibers) and may directly modulate heart rhythm, conduction, and arrhythmia susceptibility.","whyItMatters":"Arrhythmias are a major cause of cardiac death. If natriuretic peptides modulate heart rhythm, their elevation in heart failure may contribute to arrhythmia protection or susceptibility — affecting clinical management.","specificNumbers":"","methodology":"Review of immunohistochemical, molecular, and electrophysiological evidence for natriuretic peptide presence and function in the cardiac conduction system.","limitations":"Evidence for functional electrophysiological effects was indirect at time of review. The clinical significance of conduction system natriuretic peptides for arrhythmia management is speculative."},{"rthcId":"RPEP-00733","title":"Cell differentiation is a key determinant of cathelicidin LL-37/human cationic antimicrobial protein 18 expression by human colon epithelium.","authors":"Hase, Koji; Eckmann, Lars; Leopard, John D; Varki, Nissi; Kagnoff, Martin F","year":2002,"journal":"Infection and immunity, 70(2), 953-63","doi":null,"pmid":"11796631","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00734","title":"The rat arcuate nucleus integrates peripheral signals provided by leptin, insulin, and a ghrelin mimetic.","authors":"Hewson, Adrian K; Tung, Loraine Y C; Connell, David W; Tookman, Laura; Dickson, Suzanne L","year":2002,"journal":"Diabetes, 51(12), 3412-9","doi":null,"pmid":"12453894","tags":["ghrp","weight-loss","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"The arcuate nucleus integrates peripheral metabolic signals through distinct neuronal populations: ghrelin mimetic activated neurons separate from those responding to leptin and insulin, which showed overlapping activation patterns.","whyItMatters":"Understanding how the brain integrates multiple appetite signals reveals why appetite regulation is so complex and why single-target obesity drugs may have limited effectiveness.","specificNumbers":"","methodology":"Animal study using immunohistochemistry (Fos, pSTAT3) and double-labeling to map neuronal activation by leptin, insulin, and the ghrelin mimetic GHRP-6 in the rat arcuate nucleus.","limitations":"Rat arcuate mapping with acute signal presentation. Chronic physiological integration may differ from acute experimental conditions."},{"rthcId":"RPEP-00735","title":"Expression and action of the growth hormone releasing peptide ghrelin and its receptor in prostate cancer cell lines.","authors":"Jeffery, P L; Herington, A C; Chopin, L K","year":2002,"journal":"The Journal of endocrinology, 172(3), R7-11","doi":null,"pmid":"11874717","tags":["ghrp","cancer","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Prostate cancer cells expressed ghrelin, GHS-R1a, and GHS-R1b (autocrine system), with biphasic proliferative response: low ghrelin concentrations slightly stimulated while higher concentrations inhibited cell growth.","whyItMatters":"Prostate cancer is one of the most common cancers in men. Understanding ghrelin's complex effects on prostate cancer cells is crucial for assessing the safety of GH secretagogues in this population.","specificNumbers":"","methodology":"In-vitro study on prostate cancer cell lines (PC-3, LNCaP). RT-PCR for ghrelin, GHS-R1a, and GHS-R1b expression. Proliferation assays at multiple ghrelin concentrations.","limitations":"In-vitro cell line study. Biphasic responses in culture may not predict in-vivo tumor behavior. Only two cell lines tested. The physiological relevance of the concentrations tested is uncertain."},{"rthcId":"RPEP-00736","title":"Involvement of cholecystokinin/gastrin-related peptides and their receptors in clinical gastrointestinal disorders.","authors":"Jensen, Robert T","year":2002,"journal":"Pharmacology & toxicology, 91(6), 333-50","doi":null,"pmid":"12688377","tags":["neuropeptides","gut-healing"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"CCK/CCK-A receptor dysfunction is implicated in gallbladder and pancreatic diseases, while gastrin/CCK-B receptor abnormalities may contribute to GI cancer development, positioning these peptide systems as therapeutic targets.","whyItMatters":"GI diseases are extremely common. Understanding the peptide signaling dysfunction underlying them could enable targeted treatments that address root causes rather than symptoms.","specificNumbers":"","methodology":"Review of clinical and experimental evidence for CCK, gastrin, and their receptor roles across GI diseases including biliary, pancreatic, and neoplastic conditions.","limitations":"Review with varying evidence levels across diseases. The causal role of peptide receptor dysfunction versus being a consequence of disease is not always clear."},{"rthcId":"RPEP-00737","title":"Influence of chronic treatment with the growth hormone secretagogue Ipamorelin, in young female rats: somatotroph response in vitro.","authors":"Jiménez-Reina, L; Cañete, R; de la Torre, M J; Bernal, G","year":2002,"journal":"Histology and histopathology, 17(3), 707-14","doi":"10.14670/HH-17.707","pmid":"12168778","tags":["ipamorelin","hormone-optimization"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Chronic ipamorelin treatment maintained somatotroph GH-releasing responsiveness without desensitization, though GHRH and somatostatin receptor expression were modulated — adaptive changes that preserved overall drug effectiveness.","whyItMatters":"Maintaining effectiveness during chronic use is essential for GH secretagogues to serve as long-term GH replacement therapy. This study provides reassurance that ipamorelin doesn't lose its punch.","specificNumbers":"","methodology":"Animal study in young female rats with chronic ipamorelin treatment. Pituitary somatotroph responsiveness tested ex vivo. GHRH receptor and somatostatin receptor expression measured by molecular techniques.","limitations":"Young female rats; may not predict adult human responses. Receptor expression changes suggest adaptive mechanisms that could eventually affect efficacy with very long-term use."},{"rthcId":"RPEP-00738","title":"Peptides and Ageing.","authors":"Khavinson, V Kh; Anisimov, V N","year":2002,"journal":"Neuro endocrinology letters, 23 Suppl 3, 11-144","doi":"10.1159/000065611","pmid":"12374906","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00739","title":"Exploring the opioid system by gene knockout.","authors":"Kieffer, Brigitte L; Gavériaux-Ruff, Claire","year":2002,"journal":"Progress in neurobiology, 66(5), 285-306","doi":null,"pmid":"12015197","tags":["opioid-peptides","pain","addiction","anxiety-mood"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Opioid gene knockouts reveal distinct, non-redundant roles: enkephalins in analgesia and reward, beta-endorphin in stress analgesia and respiratory control, dynorphins in pain and emotional regulation — each family has a specific functional niche.","whyItMatters":"Defining the specific function of each opioid peptide family enables targeted drug development — different drugs for different conditions based on which opioid system is most relevant.","specificNumbers":"","methodology":"Review of published opioid peptide and receptor knockout mouse studies, synthesizing phenotypes across pain, reward, addiction, stress, mood, and other behavioral domains.","limitations":"Knockout mice eliminate genes from conception, allowing compensatory mechanisms. Some phenotypes may reflect developmental effects rather than adult gene function."},{"rthcId":"RPEP-00740","title":"Self-assembling peptide hydrogel fosters chondrocyte extracellular matrix production and cell division: implications for cartilage tissue repair.","authors":"Kisiday, J; Jin, M; Kurz, B; Hung, H; Semino, C; Zhang, S; Grodzinsky, A J","year":2002,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 99(15), 9996-10001","doi":null,"pmid":"12119393","tags":["peptide-design","bone-joint"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Self-assembling peptide hydrogels maintained chondrocyte phenotype, supported cell division, and promoted extracellular matrix production (GAG, type II collagen), demonstrating functional cartilage tissue formation in a peptide scaffold.","whyItMatters":"Osteoarthritis affects hundreds of millions globally with no cure. An injectable peptide gel that enables cartilage regeneration at the joint surface could transform treatment from symptom management to actual repair.","specificNumbers":"","methodology":"In-vitro study encapsulating bovine chondrocytes in self-assembling peptide hydrogels. Cell viability, proliferation, phenotype retention, and matrix production (GAG, collagen) measured over culture periods.","limitations":"In-vitro study. Translation to in-vivo joint repair requires overcoming challenges including mechanical loading, integration with existing cartilage, and immune response."},{"rthcId":"RPEP-00741","title":"Ghrelin, an orexigenic signaling molecule from the gastrointestinal tract.","authors":"Kojima, Masayasu; Kangawa, Kenji","year":2002,"journal":"Current opinion in pharmacology, 2(6), 665-8","doi":null,"pmid":"12482728","tags":["ghrp","weight-loss","receptor-signaling"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Ghrelin is the only known circulating orexigenic hormone, with meal-related fluctuations and interactions with leptin, insulin, and hypothalamic neuropeptides integrating peripheral and central appetite regulation.","whyItMatters":"Understanding ghrelin's position in the appetite regulation network enables more strategic drug development — targeting ghrelin may be most effective when combined with other appetite pathway modulation.","specificNumbers":"","methodology":"Review of ghrelin's orexigenic signaling, meal-related dynamics, interactions with other appetite hormones, and central nervous system integration pathways.","limitations":"Review from 2002 when ghrelin's full integration with the appetite network was still being mapped. Some proposed interactions were preliminary."},{"rthcId":"RPEP-00742","title":"Thymosin-alpha1 and famciclovir combination therapy activates T-cell response in patients with chronic hepatitis B virus infection in immune-tolerant phase.","authors":"Lau, G K K; Nanji, A; Hou, J; Fong, D Y T; Au, W-S; Yuen, S-T; Lin, M; Kung, H-F; Lam, S-K","year":2002,"journal":"Journal of viral hepatitis, 9(4), 280-7","doi":null,"pmid":"12081605","tags":["thymosin-alpha-1","infection","clinical-trials"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"Thymosin alpha-1 + famciclovir combination activated HBV-specific T-cell responses and achieved HBeAg seroconversion in some immune-tolerant chronic hepatitis B patients — a typically treatment-unresponsive population.","whyItMatters":"Immune-tolerant HBV carriers are the largest reservoir of the virus. If their immune tolerance can be broken with combination therapy, HBV global elimination becomes more achievable.","specificNumbers":"","methodology":"Clinical trial in immune-tolerant chronic HBV patients (high HBV DNA, normal ALT). Combined thymosin alpha-1 + famciclovir therapy. HBeAg seroconversion, HBV DNA levels, and HBV-specific T-cell responses monitored.","limitations":"Small study with limited seroconversion rate details. Immune-tolerant HBV is heterogeneous. Long-term durability of seroconversion not established."},{"rthcId":"RPEP-00743","title":"Acute central ghrelin and GH secretagogues induce feeding and activate brain appetite centers.","authors":"Lawrence, Catherine B; Snape, Amelie C; Baudoin, Florence M-H; Luckman, Simon M","year":2002,"journal":"Endocrinology, 143(1), 155-62","doi":null,"pmid":"11751604","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00744","title":"The potential of brain natriuretic peptide as a biomarker for New York Heart Association class during the outpatient treatment of heart failure.","authors":"Lee, Shang-Chiun; Stevens, Tracy L; Sandberg, Sharon M; Heublein, Denise M; Nelson, Susan M; Jougasaki, Michihisa; Redfield, Margaret M; Burnett, John C","year":2002,"journal":"Journal of cardiac failure, 8(3), 149-54","doi":null,"pmid":"12140807","tags":["natriuretic-peptides","cardiovascular","clinical-trials"],"studyType":"cross-sectional","evidenceStrength":"moderate","keyFinding":"BNP correlated most strongly with NYHA heart failure classification and treatment response in outpatients, outperforming C-terminal ANP and N-terminal ANP as a monitoring biomarker.","whyItMatters":"Monitoring heart failure treatment effectiveness requires reliable biomarkers. This study confirms BNP's superiority for outpatient monitoring, guiding clinical practice and laboratory test selection.","specificNumbers":"","methodology":"Cross-sectional study comparing C-ANP, N-ANP, and BNP levels against NYHA class in outpatient heart failure patients. Biomarker performance assessed for treatment monitoring utility.","limitations":"Cross-sectional design; serial monitoring over time would provide stronger evidence. Specific NYHA-BNP correlation coefficients not detailed. Treatment heterogeneity in outpatient population."},{"rthcId":"RPEP-00745","title":"Treatment of chronic hepatitis B: case selection and duration of therapy.","authors":"Leung, Nancy","year":2002,"journal":"Journal of gastroenterology and hepatology, 17(4), 409-14","doi":null,"pmid":"11982721","tags":["thymosin-alpha-1","infection","clinical-trials"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Chronic HBV treatment should be individualized based on viral markers, liver status, and patient characteristics, with thymosin alpha-1 offering an immune-enhancing alternative/complement to antiviral drugs across different HBV subgroups.","whyItMatters":"Hepatitis B affects 300 million people. Individualized treatment selection based on patient characteristics optimizes outcomes. Including thymosin alpha-1 in the treatment algorithm expands options.","specificNumbers":"","methodology":"Comprehensive clinical review covering treatment indications, drug comparisons, combination strategies, and duration guidelines for all chronic hepatitis B subgroups.","limitations":"2002 review; treatment landscape has evolved with tenofovir, entecavir, and ongoing cure research. Some treatment recommendations have been updated."},{"rthcId":"RPEP-00746","title":"Thymosin alpha1 accelerates restoration of T cell-mediated neutralizing antibody response in immunocompromised hosts.","authors":"Li, Chun-lin; Zhang, Ting; Saibara, Toshiji; Nemoto, Yoshihisa; Ono, Masafumi; Akisawa, Naoaki; Iwasaki, Shinji; Maeda, Takashi; Onishi, Saburo","year":2002,"journal":"International immunopharmacology, 2(1), 39-46","doi":null,"pmid":"11789668","tags":["thymosin-alpha-1","immune-function","infection"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Thymosin alpha-1 accelerated restoration of T-cell-mediated neutralizing antibody responses in immunocompromised hosts, demonstrating faster immune reconstitution through both immunomodulatory and direct intracellular mechanisms.","whyItMatters":"The period of immune vulnerability after chemotherapy or transplant is when patients are most at risk for lethal infections. Speeding up immune recovery could save lives in this critical window.","specificNumbers":"","methodology":"Animal study in immunocompromised mice. Thymosin alpha-1 administered during immune recovery. T-cell function and neutralizing antibody production measured over time compared to untreated controls.","limitations":"Mouse model. The degree of acceleration and clinical significance in humans needs confirmation. Different causes of immunocompromise may respond differently."},{"rthcId":"RPEP-00747","title":"The alpha9/alpha10-containing nicotinic ACh receptor is directly modulated by opioid peptides, endomorphin-1, and dynorphin B, proposed efferent cotransmitters in the inner ear.","authors":"Lioudyno, M I; Verbitsky, M; Glowatzki, E; Holt, J C; Boulter, J; Zadina, J E; Elgoyhen, A B; Guth, P S","year":2002,"journal":"Molecular and cellular neurosciences, 20(4), 695-711","doi":null,"pmid":"12213449","tags":["opioid-peptides","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Endomorphin-1 and dynorphin A directly modulated alpha9/alpha10 nicotinic ACh receptors (not through opioid receptors), providing a molecular mechanism for opioid peptide modulation of auditory and vestibular function.","whyItMatters":"Hearing loss and balance disorders are common. Understanding that opioid peptides directly modulate inner ear receptors could explain certain hearing conditions and guide treatment development.","specificNumbers":"","methodology":"In-vitro electrophysiology study expressing alpha9/alpha10 nAChR in Xenopus oocytes. Direct effects of endomorphin-1 and dynorphin A on receptor currents measured by two-electrode voltage clamp.","limitations":"Heterologous expression system (oocytes). The physiological concentrations of opioid peptides at auditory synapses are unknown. Functional hearing/balance consequences not measured."},{"rthcId":"RPEP-00748","title":"Downregulation of glucocorticoid receptors of liver cytosols and the role of the inflammatory cytokines in pathological stress in scalded rats.","authors":"Liu, Du-hu; Su, Yong-ping; Zhang, Wei; Lou, Shu-fen; Ran, Xin-ze; Gao, Jing-sheng; Cheng, Tian-min","year":2002,"journal":"Burns : journal of the International Society for Burn Injuries, 28(4), 315-20","doi":null,"pmid":"12052369","tags":["neuropeptides","inflammation","wound-healing"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Pathological burn stress downregulated liver glucocorticoid receptors through inflammatory cytokine (TNF-α, IL-1, IL-6) action, explaining cortisol resistance and uncontrolled inflammation during severe trauma.","whyItMatters":"Understanding why cortisol fails during severe stress explains treatment failures and guides interventions to restore anti-inflammatory signaling when it's most needed.","specificNumbers":"","methodology":"Animal study in burn-injured rats. Liver glucocorticoid receptor density measured by binding assays. Plasma corticosterone and inflammatory cytokines quantified. Adrenomedullin and substance P also measured.","limitations":"Rat burn model. The degree of receptor downregulation in humans and its clinical significance need confirmation."},{"rthcId":"RPEP-00749","title":"Cell and molecular biology of the multifunctional peptide, adrenomedullin.","authors":"López, José; Martínez, Alfredo","year":2002,"journal":"International review of cytology, 221, 1-92","doi":null,"pmid":"12455746","tags":["neuropeptides","cardiovascular","inflammation"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Adrenomedullin functions as a vasodilator, growth regulator, neurotransmitter, anti-inflammatory agent, and hormone modulator through CRLR/RAMP receptor complexes, with therapeutic implications across cardiovascular, inflammatory, and neoplastic diseases.","whyItMatters":"Understanding ADM's full functional range is essential for developing therapeutics that harness its beneficial effects while managing its diverse actions across organ systems.","specificNumbers":"","methodology":"Comprehensive review of adrenomedullin cell and molecular biology covering receptor characterization, signaling pathways, tissue expression, and diverse biological functions.","limitations":"Review of ADM's expanding biology; therapeutic translation was still largely conceptual at the time."},{"rthcId":"RPEP-00750","title":"Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure.","authors":"Maisel, Alan S; Krishnaswamy, Padma; Nowak, Richard M; McCord, James; Hollander, Judd E; Duc, Philippe; Omland, Torbjørn; Storrow, Alan B; Abraham, William T; Wu, Alan H B; Clopton, Paul; Steg, Philippe G; Westheim, Arne; Knudsen, Catherine Wold; Perez, Alberto; Kazanegra, Radmila; Herrmann, Howard C; McCullough, Peter A","year":2002,"journal":"The New England journal of medicine, 347(3), 161-7","doi":null,"pmid":"12124404","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In a prospective study of 1,586 emergency department patients presenting with acute dyspnea, B-type natriuretic peptide (BNP) measured by bedside assay was more accurate than any historical finding, physical examination, or laboratory value for identifying congestive heart failure.\n\nAt a cutoff of 100 pg/mL, BNP had a diagnostic accuracy of 83.4%. At levels below 50 pg/mL, the negative predictive value was 96% — meaning very low BNP effectively rules out heart failure. Of the patients studied, 47% had heart failure, 49% had non-cardiac causes of dyspnea, and 5% had dyspnea from non-cardiac causes despite a history of left ventricular dysfunction. BNP added significant independent predictive power to other clinical variables in multivariate analysis.","whyItMatters":"This study, published in the New England Journal of Medicine, was one of the most influential papers establishing BNP testing as a standard tool in emergency medicine. Before bedside BNP testing, distinguishing heart failure from other causes of shortness of breath relied heavily on clinical judgment, chest X-rays, and time-consuming workups. A simple, rapid blood test that outperforms clinical assessment fundamentally changed how heart failure is diagnosed in the acute setting.","specificNumbers":"","methodology":"Prospective, multicenter study enrolling 1,586 patients who presented to emergency departments with acute dyspnea (shortness of breath). BNP was measured using a bedside point-of-care assay. The final diagnosis of congestive heart failure was adjudicated by two independent cardiologists who were blinded to the BNP results, providing an unbiased gold standard for comparison.","limitations":"The 83.4% accuracy means roughly 1 in 6 patients could be misclassified. BNP levels can be elevated in conditions other than heart failure (kidney disease, pulmonary embolism, sepsis), leading to false positives. Obesity can suppress BNP levels, potentially causing false negatives. The study population was from emergency departments, so results may not generalize to outpatient or primary care settings. The optimal cutoff value has been debated since publication."},{"rthcId":"RPEP-00751","title":"Thymosin alpha1 inhibits mammary carcinogenesis in Fisher rats.","authors":"Moody, Terry W; Tuthill, Cynthia; Badamchian, Mahnaz; Goldstein, Allan L","year":2002,"journal":"Peptides, 23(5), 1011-4","doi":null,"pmid":"12084534","tags":["thymosin-alpha-1","cancer","immune-function"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Thymosin alpha-1 significantly inhibited NMU-induced mammary carcinogenesis in Fisher rats, reducing both tumor incidence and multiplicity, demonstrating cancer prevention through immune enhancement.","whyItMatters":"Cancer prevention is more effective than cancer treatment. A non-toxic immune enhancer that prevents breast cancer development could complement screening programs for high-risk women.","specificNumbers":"","methodology":"Animal study in Fisher rats. NMU (10 mg IP) to induce mammary carcinomas. Thymosin alpha-1 treatment during/after carcinogen exposure. Tumor development assessed at 3 months and beyond.","limitations":"Rat chemical carcinogenesis model. Human breast cancer has more complex etiology. Whether immune enhancement can prevent hormone-driven breast cancer in humans is unknown."},{"rthcId":"RPEP-00752","title":"Neuropeptide-Y, cortisol, and subjective distress in humans exposed to acute stress: replication and extension of previous report.","authors":"Morgan, Charles A; Rasmusson, Ann M; Wang, Sheila; Hoyt, Gary; Hauger, Richard L; Hazlett, Gary","year":2002,"journal":"Biological psychiatry, 52(2), 136-42","doi":null,"pmid":"12114005","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00753","title":"Neuroendocrine and peripheral activities of ghrelin: implications in metabolism and obesity.","authors":"Muccioli, Giampiero; Tschöp, Matthias; Papotti, Mauro; Deghenghi, Romano; Heiman, Mark; Ghigo, Ezio","year":2002,"journal":"European journal of pharmacology, 440(2-3), 235-54","doi":null,"pmid":"12007539","tags":["ghrp","weight-loss","hormone-optimization","cardiovascular"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Ghrelin's peripheral metabolic actions — orexigenic signaling, adipogenic activity, and cardiovascular protection — establish it as a master metabolic coordinator with therapeutic targets for obesity, cachexia, and cardiovascular disease.","whyItMatters":"Metabolism is interconnected. Ghrelin's simultaneous control of appetite, fat storage, and heart function means manipulating this system has implications across metabolic and cardiovascular medicine.","specificNumbers":"","methodology":"Review of ghrelin's neuroendocrine and peripheral metabolic activities, covering appetite regulation, adipose tissue effects, and cardiovascular actions.","limitations":"Review repeating themes from similar ghrelin reviews. Some peripheral effects were still being characterized at the time."},{"rthcId":"RPEP-00754","title":"Endomorphins and related opioid peptides.","authors":"Okada, Yoshio; Tsuda, Yuko; Bryant, Sharon D; Lazarus, Lawrence H","year":2002,"journal":"Vitamins and hormones, 65, 257-79","doi":null,"pmid":"12481550","tags":["opioid-peptides","pain"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Endomorphins 1 and 2 are the most mu-opioid selective endogenous peptides, with potent analgesia and distinct pharmacological profiles suggesting separate roles in pain modulation and unique therapeutic potential.","whyItMatters":"Current opioid drugs lack selectivity, causing addiction and side effects. Endomorphins' exceptional mu-selectivity provides a template for designing cleaner, more targeted analgesics.","specificNumbers":"","methodology":"Comprehensive review of endomorphin discovery, receptor pharmacology, tissue distribution, analgesic properties, and therapeutic implications.","limitations":"Endomorphins as peptides have limited stability and bioavailability. Some pharmacological characterizations were still preliminary."},{"rthcId":"RPEP-00755","title":"Comparison of plasma levels of mature adrenomedullin and natriuretic peptide as markers of cardiac function in hemodialysis patients with coronary artery disease.","authors":"Osajima, Akihiko; Okazaki, Masahiro; Tamura, Masahito; Anai, Hirofumi; Kabashima, Narutoshi; Suda, Takeshi; Iwamoto, Masako; Ota, Takayuki; Watanabe, Yuujiro; Kanegae, Kaori; Nakashima, Yasuhide","year":2002,"journal":"Nephron, 92(4), 832-9","doi":null,"pmid":"12399629","tags":["natriuretic-peptides","neuropeptides","cardiovascular","kidney"],"studyType":"cross-sectional","evidenceStrength":"moderate","keyFinding":"Mature adrenomedullin and BNP provided complementary cardiac information in hemodialysis patients: BNP reflected LV dysfunction more specifically, while mAM reflected broader cardiovascular status including vascular and renal components.","whyItMatters":"Dialysis patients have extremely high cardiovascular mortality. Using complementary biomarkers (BNP for heart, mAM for heart + vessels) could improve cardiovascular risk assessment in this high-risk population.","specificNumbers":"","methodology":"Cross-sectional study in hemodialysis patients comparing mature adrenomedullin, ANP, and BNP with echocardiographic cardiac function parameters.","limitations":"Cross-sectional in hemodialysis patients. Dialysis timing affects peptide levels. Specific mAM assay may vary between studies."},{"rthcId":"RPEP-00756","title":"Modulatory role of thymosin-alpha-1 in normal bone-marrow haematopoiesis and its effect on myelosuppression in T-cell lymphoma bearing mice.","authors":"Paul, Saki; Sodhi, Ajit","year":2002,"journal":"Immunology letters, 82(3), 171-82","doi":null,"pmid":"12036599","tags":["thymosin-alpha-1","immune-function","cancer"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Thymosin alpha-1 restored suppressed bone marrow hematopoiesis in T-cell lymphoma mice, increasing colony-forming units (CFU-GM, BFU-E, CFU-GEMM) and peripheral blood counts across all lineages.","whyItMatters":"Cancer and chemotherapy both suppress blood cell production. A peptide that restores bone marrow function could reduce the need for blood transfusions and growth factor injections in cancer patients.","specificNumbers":"","methodology":"Animal study in mice bearing T-cell lymphomas causing myelosuppression. Thymosin alpha-1 administered. Peripheral blood counts, bone marrow cellularity, and colony-forming assays measured across blood cell lineages.","limitations":"Mouse T-cell lymphoma model. The mechanism of hematopoietic restoration (direct bone marrow effect vs indirect immune modulation) was not fully determined."},{"rthcId":"RPEP-00757","title":"Growth hormone secretagogue (GHS) analogue, hexarelin stimulates GH from peripheral lymphocytes.","authors":"Poppi, L; Dixit, V D; Baratta, M; Giustina, A; Tamanini, C; Parvizi, N","year":2002,"journal":"Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association, 110(7), 343-7","doi":null,"pmid":"12397533","tags":["ghrp","immune-function","hormone-optimization"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Hexarelin and GHRH stimulated GH production directly from porcine and human lymphocytes, demonstrating functional GHS-R and GHRH-R on immune cells with a local GH autocrine/paracrine system.","whyItMatters":"A local GH system in immune cells means GH secretagogues could directly boost immune function — not just indirectly through pituitary GH release. This direct immune effect adds therapeutic value.","specificNumbers":"","methodology":"In-vitro study using cultured porcine and human lymphocytes. Hexarelin and GHRH stimulation with GH measurement in culture supernatant by RIA. Receptor expression confirmed.","limitations":"In-vitro lymphocyte culture. The amount of GH produced locally may be small relative to pituitary output. Physiological significance uncertain."},{"rthcId":"RPEP-00758","title":"Orexins (hypocretins): their role in appetite and arousal.","authors":"Preti, Antonio","year":2002,"journal":"Current opinion in investigational drugs (London, England : 2000), 3(8), 1199-206","doi":null,"pmid":"12211415","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00759","title":"Dietary peptides induce satiety via cholecystokinin-A and peripheral opioid receptors in rats.","authors":"Pupovac, Jelena; Anderson, G Harvey","year":2002,"journal":"The Journal of nutrition, 132(9), 2775-80","doi":null,"pmid":"12221244","tags":["opioid-peptides","bioactive-food-peptides","weight-loss"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Dietary peptides from protein digestion induced satiety through both CCK-A and peripheral opioid receptor pathways, with the relative contribution of each pathway varying by protein source — different foods activate different satiety signals.","whyItMatters":"Understanding which satiety signals different proteins activate could guide dietary recommendations for weight management — choosing protein sources that maximize satiety through multiple pathways.","specificNumbers":"","methodology":"Animal feeding study in rats. Dietary protein digests from different sources administered. Food intake measured with and without CCK-A receptor antagonist (devazepide) and peripheral opioid antagonist (naloxone methiodide).","limitations":"Rat feeding study. Protein digestion in vitro may differ from in vivo. The specific peptide fragments responsible for each pathway were not identified."},{"rthcId":"RPEP-00760","title":"Structure-activity studies of 14-helical antimicrobial beta-peptides: probing the relationship between conformational stability and antimicrobial potency.","authors":"Raguse, Tami L; Porter, Emilie A; Weisblum, Bernard; Gellman, Samuel H","year":2002,"journal":"Journal of the American Chemical Society, 124(43), 12774-85","doi":null,"pmid":"12392424","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00761","title":"Corticotropin-releasing factor receptors 1 and 2 in anxiety and depression.","authors":"Reul, Johannes M H M; Holsboer, Florian","year":2002,"journal":"Current opinion in pharmacology, 2(1), 23-33","doi":null,"pmid":"11786305","tags":["neuropeptides","anxiety-mood"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"CRF1 promotes anxiety and depression while CRF2 may have opposing anxiolytic/stress-recovery effects, with urocortins as natural CRF2-preferring ligands enabling receptor-specific therapeutic targeting.","whyItMatters":"Understanding that anxiety and stress recovery use different CRF receptors enables more targeted treatments — blocking anxiety without blocking stress recovery.","specificNumbers":"","methodology":"Review of CRF receptor pharmacology, knockout mouse studies, and urocortin biology in anxiety and depression.","limitations":"Brief review. CRF2's anxiolytic role is more complex than simple opposition to CRF1. Clinical translation has been challenging."},{"rthcId":"RPEP-00762","title":"Clinical pharmacology of human growth hormone and its secretagogues.","authors":"Root, Allen W; Root, Michael J","year":2002,"journal":"Current drug targets. Immune, endocrine and metabolic disorders, 2(1), 27-52","doi":null,"pmid":"12477295","tags":["ghrp","hormone-optimization","clinical-trials"],"studyType":"review","evidenceStrength":"strong","keyFinding":"GH secretagogues (GHRP-6, hexarelin, MK-677) offer clinical advantages over GH injections: oral availability, physiological pulsatile release patterns, and multiple applications from GH deficiency to aging, obesity, and critical illness.","whyItMatters":"This serves as the definitive clinical pharmacology reference for practitioners and researchers working with GH and GH secretagogues across all therapeutic applications.","specificNumbers":"","methodology":"Comprehensive clinical pharmacology review covering GH biology, regulation, GH secretagogue pharmacology, and clinical applications across multiple indications.","limitations":"Review from 2002. Some clinical applications were still in development. Long-term safety data for chronic GH secretagogue use was limited."},{"rthcId":"RPEP-00763","title":"Peptides from the N-terminal end of bovine lactoferrin induce apoptosis in human leukemic (HL-60) cells.","authors":"Roy, M K; Kuwabara, Y; Hara, K; Watanabe, Y; Tamai, Y","year":2002,"journal":"Journal of dairy science, 85(9), 2065-74","doi":null,"pmid":"12362437","tags":["antimicrobial-peptides","cancer"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Bovine lactoferricin induced apoptosis in human HL-60 leukemia cells more potently than intact lactoferrin, with activity dependent on native protein structure, demonstrating structure-specific anti-leukemic killing.","whyItMatters":"Leukemia needs new treatments, especially for resistant cases. A milk-derived peptide that triggers cancer cell suicide through apoptosis offers a natural, potentially less toxic approach to blood cancer therapy.","specificNumbers":"","methodology":"In-vitro study exposing human HL-60 myeloid leukemia cells to lactoferrin, lactoferricin, and modified forms. Cell viability, apoptosis markers, and structure-activity relationships assessed.","limitations":"Single leukemia cell line (HL-60). In-vitro apoptosis doesn't guarantee in-vivo anti-leukemic efficacy. Therapeutic concentrations may differ from achievable blood levels."},{"rthcId":"RPEP-00764","title":"Bosentan therapy for pulmonary arterial hypertension.","authors":"Rubin, Lewis J; Badesch, David B; Barst, Robyn J; Galie, Nazzareno; Black, Carol M; Keogh, Anne; Pulido, Tomas; Frost, Adaani; Roux, Sebastien; Leconte, Isabelle; Landzberg, Michael; Simonneau, Gerald","year":2002,"journal":"The New England journal of medicine, 346(12), 896-903","doi":null,"pmid":"11907289","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00765","title":"Chicken ghrelin and growth hormone-releasing peptide-2 inhibit food intake of neonatal chicks.","authors":"Saito, Ei-suke; Kaiya, Hiroyuki; Takagi, Tomo; Yamasaki, Izumi; Denbow, D Michael; Kangawa, Kenji; Furuse, Mitsuhiro","year":2002,"journal":"European journal of pharmacology, 453(1), 75-9","doi":null,"pmid":"12393062","tags":["ghrp","weight-loss"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Intracerebroventricular chicken ghrelin and GHRP-2 inhibited food intake in neonatal chicks — the opposite of the appetite-stimulating effect in mammals — revealing a fundamental species difference in ghrelin signaling.","whyItMatters":"This species difference reveals that ghrelin's appetite function isn't universal — it evolved differently in birds. This has implications for understanding appetite regulation evolution and for extrapolating mammalian drug research across species.","specificNumbers":"","methodology":"Animal study using ICV injection of chicken ghrelin and GHRP-2 in neonatal chicks. Food intake measured following central administration compared to saline controls.","limitations":"Neonatal chicks may respond differently from adult chickens. ICV administration bypasses normal physiological delivery. The mechanism of the reversed effect was not determined."},{"rthcId":"RPEP-00766","title":"The human antimicrobial peptide LL-37 is a multifunctional modulator of innate immune responses.","authors":"Scott, Monisha G; Davidson, Donald J; Gold, Michael R; Bowdish, Dawn; Hancock, Robert E W","year":2002,"journal":"Journal of immunology (Baltimore, Md. : 1950), 169(7), 3883-91","doi":null,"pmid":"12244186","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00767","title":"Mode of action of membrane active antimicrobial peptides.","authors":"Shai, Yechiel","year":2002,"journal":"Biopolymers, 66(4), 236-48","doi":null,"pmid":"12491537","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00768","title":"Macrocyclic hairpin mimetics of the cationic antimicrobial peptide protegrin I: a new family of broad-spectrum antibiotics.","authors":"Shankaramma, Sasalu C; Athanassiou, Zafiria; Zerbe, Oliver; Moehle, Kerstin; Mouton, Carole; Bernardini, Francesca; Vrijbloed, Jan W; Obrecht, Daniel; Robinson, John A","year":2002,"journal":"Chembiochem : a European journal of chemical biology, 3(11), 1126-33","doi":null,"pmid":"12404639","tags":["antimicrobial-peptides","cyclic-peptides","infection","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Macrocyclic hairpin mimetics of protegrin I demonstrated broad-spectrum antibacterial activity including against resistant strains, with improved stability over linear peptide antibiotics and activity maintained in challenging conditions.","whyItMatters":"Antibiotic resistance is a global health emergency. Converting natural antimicrobial peptides into stable macrocyclic drugs could generate urgently needed new antibiotic classes.","specificNumbers":"","methodology":"In-vitro antimicrobial study. Macrocyclic protegrin analogs synthesized and tested against panels of gram-positive and gram-negative bacteria, including resistant strains. Activity in serum and salt conditions assessed.","limitations":"In-vitro activity. In-vivo efficacy, pharmacokinetics, and toxicity not assessed. Cost of macrocyclic peptide manufacturing may limit clinical development."},{"rthcId":"RPEP-00769","title":"Comparison of the effects of omapatrilat and lisinopril on circulating neurohormones and cytokines in patients with chronic heart failure.","authors":"Sheth, Tej; Parker, Tom; Block, Alan; Hall, Christian; Adam, Albert; Pfeffer, Mark A; Stewart, Duncan J; Qian, Chunlin; Rouleau, Jean L","year":2002,"journal":"The American journal of cardiology, 90(5), 496-500","doi":null,"pmid":"12208409","tags":["natriuretic-peptides","cardiovascular","inflammation"],"studyType":"RCT","evidenceStrength":"moderate","keyFinding":"Omapatrilat and lisinopril had equivalent effects on angiotensin II, aldosterone, and inflammatory cytokines in CHF, but omapatrilat additionally reduced natriuretic peptide levels, suggesting superior cardiac functional improvement.","whyItMatters":"Direct comparison shows vasopeptidase inhibition provides all ACE inhibitor benefits plus additional natriuretic peptide modulation — supporting the dual-inhibition concept despite clinical limitations.","specificNumbers":"","methodology":"Randomized controlled trial comparing omapatrilat versus lisinopril in chronic heart failure patients. Neurohormones (ANP, BNP, angiotensin II, aldosterone, endothelin), inflammatory cytokines (TNF-α, IL-6), and hemodynamics measured.","limitations":"Omapatrilat was subsequently limited by angioedema risk. The NP reduction mechanism (improved function vs degradation) could not be definitively determined."},{"rthcId":"RPEP-00770","title":"Hypothalamic growth hormone secretagogue receptor regulates growth hormone secretion, feeding, and adiposity.","authors":"Shuto, Yujin; Shibasaki, Tamotsu; Otagiri, Asuka; Kuriyama, Hideki; Ohata, Hisayuki; Tamura, Hideki; Kamegai, Jun; Sugihara, Hitoshi; Oikawa, Shinichi; Wakabayashi, Ichiji","year":2002,"journal":"The Journal of clinical investigation, 109(11), 1429-36","doi":null,"pmid":"12045256","tags":["ghrp","hormone-optimization","weight-loss"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Hypothalamic GHS-R antisense knockdown reduced both GH secretion and body weight/food intake in rats, confirming the hypothalamic receptor's dual role in mediating GH release and appetite regulation by ghrelin/GHS.","whyItMatters":"Confirming the hypothalamic GHS-R controls both GH and appetite means drugs targeting this receptor will inevitably affect both — a key consideration for GH secretagogue therapy.","specificNumbers":"","methodology":"Animal study using intracerebroventricular antisense oligonucleotides to knock down GHS-R in the rat hypothalamus. GH secretion, food intake, and body weight measured following receptor reduction.","limitations":"Antisense knockdown is partial and temporary. The specific hypothalamic nuclei affected were not precisely mapped."},{"rthcId":"RPEP-00771","title":"Pentadecapeptide BPC 157 attenuates chronic amphetamine-induced behavior disturbances.","authors":"Sikiric, Predrag; Jelovac, Nikola; Jelovac-Gjeldum, Andjelka; Dodig, Goran; Staresinic, Mario; Anic, Tomislav; Zoricic, Ivan; Rak, Davor; Perovic, Darko; Aralica, Gorana; Buljat, Gojko; Prkacin, Ingrid; Lovric-Bencic, Martina; Separovic, Jadranka; Seiwerth, Sven; Rucman, Rudolf; Petek, Marijan; Turkovic, Branko; Ziger, Tihomil; Boban-Blagaic, Alenka; Bedekovic, Vlado; Tonkic, Ante; Babic, Slaven","year":2002,"journal":"Acta pharmacologica Sinica, 23(5), 412-22","doi":null,"pmid":"11978191","tags":["bpc-157","neuroprotection","anxiety-mood","addiction"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"BPC-157 attenuated chronic amphetamine-induced tolerance, behavioral sensitization, and withdrawal disturbances in rats, demonstrating comprehensive dopamine system stabilization against stimulant drug-induced neuroplasticity.","whyItMatters":"Stimulant addiction (amphetamine, methamphetamine) is devastating and has limited treatments. A peptide that comprehensively protects against chronic stimulant brain changes could transform addiction medicine.","specificNumbers":"","methodology":"Animal study in rats with chronic amphetamine exposure. BPC-157 co-administered at microgram and nanogram doses. Tolerance, sensitization (cross-sensitization), and withdrawal behaviors measured across multiple timepoints.","limitations":"Rat model. Chronic amphetamine differs from human addiction patterns. The specific dopamine system mechanisms were not fully characterized."},{"rthcId":"RPEP-00772","title":"Discriminating 3(10)- from alpha-helices: vibrational and electronic CD and IR absorption study of related Aib-containing oligopeptides.","authors":"Silva, R A Gangani D; Yasui, Sritana C; Kubelka, Jan; Formaggio, Fernando; Crisma, Marco; Toniolo, Claudio; Keiderling, Timothy A","year":2002,"journal":"Biopolymers, 65(4), 229-43","doi":null,"pmid":"12382284","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00773","title":"Involvement of mitogen-activated protein kinases in the signal transduction pathway of bone marrow-derived macrophage activation in response to in vitro treatment with thymosin alpha 1.","authors":"Sodhi, Ajit; Paul, Saki","year":2002,"journal":"International immunopharmacology, 2(1), 47-58","doi":null,"pmid":"11789669","tags":["thymosin-alpha-1","cancer","immune-function","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Thymosin alpha-1 activated anti-tumor macrophages through p38 MAPK and ERK signaling pathways, with pathway inhibition blocking the anti-tumor effect, identifying the specific intracellular mechanism of thymosin alpha-1's immunostimulatory action.","whyItMatters":"Knowing exactly how thymosin alpha-1 activates immune cells enables optimization of its use and combination with other immunotherapies that work through different signaling pathways.","specificNumbers":"","methodology":"In-vitro study using bone marrow-derived macrophages. Thymosin alpha-1 stimulation with measurement of MAPK pathway activation (p38, ERK, JNK). Selective pathway inhibitors tested for effect on macrophage anti-tumor activation.","limitations":"In-vitro macrophage study. The signaling pathway activation in vivo and in the tumor microenvironment may differ. Single cell type studied."},{"rthcId":"RPEP-00774","title":"Effects of Selank on behavioral reactions and activities of plasma enkephalin-degrading enzymes in mice with different phenotypes of emotional and stress reactions.","authors":"Sokolov, O Yu; Meshavkin, V K; Kost, N V; Zozulya, A A","year":2002,"journal":"Bulletin of experimental biology and medicine, 133(2), 133-5","doi":null,"pmid":"12432865","tags":["selank","anxiety-mood","opioid-peptides"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Selank reduced anxiety behavior in naturally anxious BALB/c mice while modifying enkephalin-degrading enzyme activity, with the anxiolytic effect phenotype-dependent — working most in animals with the greatest enkephalin degradation.","whyItMatters":"The phenotype-dependent response suggests Selank works best in individuals with genuine enkephalin deficiency — a potential biomarker for predicting who will respond to this anxiolytic.","specificNumbers":"","methodology":"Animal behavioral study comparing Selank effects in anxious (BALB/c) versus calm (C57BL/6) mice. Anxiety-like behavior and plasma enkephalin-degrading enzyme activity measured before and after treatment.","limitations":"Mouse study using inbred strains. Human anxiety is more complex than mouse strain differences. Small sample inherent to behavioral pharmacology studies."},{"rthcId":"RPEP-00775","title":"Alteration in endogenous opioid systems due to chronic inflammatory pain conditions.","authors":"Spetea, Mariana; Rydelius, Gustav; Nylander, Ingrid; Ahmed, Mahmood; Bileviciute-Ljungar, Indre; Lundeberg, Thomas; Svensson, Stefan; Kreicbergs, Andris","year":2002,"journal":"European journal of pharmacology, 435(2-3), 245-52","doi":null,"pmid":"11821033","tags":["opioid-peptides","pain","inflammation","bone-joint"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Chronic arthritic pain produced region-specific alterations in dynorphin B, met-enkephalin, and opioid receptor levels across brain, spinal cord, and pituitary, demonstrating multi-level opioid system adaptation to chronic inflammatory pain.","whyItMatters":"Understanding how chronic pain rewires the opioid system explains why chronic pain patients respond differently to medications and guides development of region-targeted pain therapies.","specificNumbers":"","methodology":"Animal study in rats with adjuvant-induced chronic arthritis. Opioid peptide concentrations and receptor densities measured in discrete brain regions, lumbar spinal cord, and pituitary.","limitations":"Rat arthritis model. Human chronic arthritis may produce different patterns. Single timepoint measurement doesn't capture dynamic changes."},{"rthcId":"RPEP-00776","title":"Apelin, the novel endogenous ligand of the orphan receptor APJ, regulates cardiac contractility.","authors":"Szokodi, István; Tavi, Pasi; Földes, Gábor; Voutilainen-Myllylä, Sari; Ilves, Mika; Tokola, Heikki; Pikkarainen, Sampsa; Piuhola, Jarkko; Rysä, Jaana; Tóth, Miklós; Ruskoaho, Heikki","year":2002,"journal":"Circulation research, 91(5), 434-40","doi":null,"pmid":"12215493","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00777","title":"Evidence for in vivo production of Humanin peptide, a neuroprotective factor against Alzheimer's disease-related insults.","authors":"Tajima, Hirohisa; Niikura, Takako; Hashimoto, Yuichi; Ito, Yuko; Kita, Yoshiko; Terashita, Kenzo; Yamazaki, Kazuto; Koto, Atsuo; Aiso, Sadakazu; Nishimoto, Ikuo","year":2002,"journal":"Neuroscience letters, 324(3), 227-31","doi":null,"pmid":"12009529","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00778","title":"Intrathecally administered big dynorphin, a prodynorphin-derived peptide, produces nociceptive behavior through an N-methyl-D-aspartate receptor mechanism.","authors":"Tan-No, Koichi; Esashi, Akihisa; Nakagawasai, Osamu; Niijima, Fukie; Tadano, Takeshi; Sakurada, Chikai; Sakurada, Tsukasa; Bakalkin, Georgy; Terenius, Lars; Kisara, Kensuke","year":2002,"journal":"Brain research, 952(1), 7-14","doi":null,"pmid":"12363399","tags":["opioid-peptides","pain","neuroprotection"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Intrathecal big dynorphin at femtomole doses caused nociceptive behavior through NMDA receptor activation (blocked by MK-801) but not through opioid receptors (not blocked by naloxone), with higher doses causing reversible paralysis.","whyItMatters":"In chronic pain conditions where dynorphin is elevated, big dynorphin may paradoxically CAUSE pain through NMDA receptors — explaining the pain-promoting role of dynorphin in some chronic pain states.","specificNumbers":"","methodology":"Animal study in mice with intrathecal injection of big dynorphin at graded doses. Pain behavior and paralysis assessed. MK-801 (NMDA antagonist) and naloxone (opioid antagonist) used to dissect mechanisms.","limitations":"Mouse study with intrathecal injection of a precursor peptide at extremely low doses. The physiological relevance of big dynorphin at these spinal concentrations is uncertain."},{"rthcId":"RPEP-00779","title":"GH-releasing peptide-2 increases fat mass in mice lacking NPY: indication for a crucial mediating role of hypothalamic agouti-related protein.","authors":"Tschöp, Matthias; Statnick, Michael A; Suter, Todd M; Heiman, Mark L","year":2002,"journal":"Endocrinology, 143(2), 558-68","doi":null,"pmid":"11796511","tags":["ghrp","weight-loss","hormone-optimization","neuropeptides"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"GHRP-2 increased fat mass in NPY knockout mice, demonstrating that GH secretagogue-induced adiposity is mediated by hypothalamic AgRP rather than NPY, identifying a critical alternative pathway for ghrelin's metabolic effects.","whyItMatters":"Identifying AgRP as the mediator of ghrelin-induced fat gain provides a more specific therapeutic target. Blocking AgRP could potentially prevent the unwanted weight gain from GH secretagogues.","specificNumbers":"","methodology":"Animal study comparing GHRP-2 effects on body composition in NPY knockout versus wild-type mice. Fat mass, food intake, and hypothalamic neuropeptide expression measured.","limitations":"NPY knockout mice may have compensatory mechanisms. The role of AgRP was inferred rather than directly proven. Other pathways may also contribute."},{"rthcId":"RPEP-00780","title":"Hypophysectomy prevents ghrelin-induced adiposity and increases gastric ghrelin secretion in rats.","authors":"Tschöp, Matthias; Flora, David B; Mayer, John P; Heiman, Mark L","year":2002,"journal":"Obesity research, 10(10), 991-9","doi":null,"pmid":"12376579","tags":["ghrp","hormone-optimization","weight-loss"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Ghrelin-induced adiposity required intact pituitary function (eliminated by hypophysectomy), while gastric ghrelin secretion paradoxically increased after pituitary removal — revealing pituitary-to-stomach feedback regulation of ghrelin.","whyItMatters":"The pituitary-stomach ghrelin feedback loop means GH therapy or GH deficiency could affect ghrelin levels and appetite — clinically important for patients receiving GH treatment.","specificNumbers":"","methodology":"Animal study in rats comparing ghrelin effects in intact versus hypophysectomized animals. Body composition, food intake, and gastric ghrelin secretion measured.","limitations":"Hypophysectomy removes ALL pituitary hormones, not just GH. The specific pituitary hormone(s) suppressing gastric ghrelin were not identified."},{"rthcId":"RPEP-00781","title":"A role for the melanocortin 4 receptor in sexual function.","authors":"Van der Ploeg, Lex H T; Martin, William J; Howard, Andrew D; Nargund, Ravi P; Austin, Christopher P; Guan, Xiaoming; Drisko, Jennifer; Cashen, Doreen; Sebhat, Iyassu; Patchett, Arthur A; Figueroa, David J; DiLella, Anthony G; Connolly, Brett M; Weinberg, David H; Tan, Carina P; Palyha, Oksana C; Pong, Sheng-Shung; MacNeil, Tanya; Rosenblum, Charles; Vongs, Aurawan; Tang, Rui; Yu, Hong; Sailer, Andreas W; Fong, Tung Ming; Huang, Cathy; Tota, Michael R; Chang, Ray S; Stearns, Ralph; Tamvakopoulos, Constantin; Christ, George; Drazen, Deborah L; Spar, Brian D; Nelson, Randy J; MacIntyre, D Euan","year":2002,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 99(17), 11381-6","doi":null,"pmid":"12172010","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00782","title":"Impact of estradiol supplementation on dual peptidyl drive of GH secretion in postmenopausal women.","authors":"Veldhuis, J D; Evans, W S; Bowers, C Y","year":2002,"journal":"The Journal of clinical endocrinology and metabolism, 87(2), 859-66","doi":null,"pmid":"11836333","tags":["ghrp","hormone-optimization","fertility"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"Oral E2 selectively enhanced the GHRP-2 hypothalamic signaling component during combined GHRP-2/GHRH stimulation while reducing somatostatin restraint in postmenopausal women, revealing pathway-specific estrogen modulation of dual-peptide GH stimulation.","whyItMatters":"This precision understanding of estrogen's effects on each GH-regulatory pathway enables optimized combination therapy — using estrogen to enhance GHRP-2 effectiveness while managing GHRH response.","specificNumbers":"","methodology":"Clinical trial in postmenopausal women with combined continuous GHRP-2 + GHRH IV infusion. Oral E2 versus placebo. 10-minute blood sampling for GH deconvolution analysis to dissect hypothalamic vs pituitary components.","limitations":"Small sample. Oral E2 (first-pass liver effects). Intensive protocol limits clinical translatability. Short-term E2 effects may differ from chronic use."},{"rthcId":"RPEP-00783","title":"Increased Staphylococcus-killing activity of an antimicrobial peptide, lactoferricin B, with minocycline and monoacylglycerol.","authors":"Wakabayashi, Hiroyuki; Teraguchi, Susumu; Tamura, Yoshitaka","year":2002,"journal":"Bioscience, biotechnology, and biochemistry, 66(10), 2161-7","doi":null,"pmid":"12450127","tags":["antimicrobial-peptides","infection"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Lactoferricin B synergized with sub-inhibitory minocycline and monoacylglycerol for enhanced killing of S. aureus including MRSA, achieving bactericidal activity at concentrations ineffective individually.","whyItMatters":"MRSA kills tens of thousands annually. Synergistic combinations using natural antimicrobial peptides could overcome resistance while reducing the antibiotic doses needed — addressing both efficacy and resistance development.","specificNumbers":"","methodology":"In-vitro antimicrobial study. Lactoferricin B combined with minocycline or monoacylglycerol at sub-inhibitory concentrations. Synergy assessed against S. aureus strains including MRSA by time-kill and checkerboard assays.","limitations":"In-vitro synergy. In-vivo combination efficacy, pharmacokinetics, and safety need assessment. Monoacylglycerol is a surfactant, not a standard drug."},{"rthcId":"RPEP-00784","title":"Roles of endogenous opioid peptides in modulation of nocifensive response to formalin.","authors":"Wu, Hsiang-En; Hung, Kuei-Chun; Mizoguchi, Hirokazu; Nagase, Hiroshi; Tseng, Leon F","year":2002,"journal":"The Journal of pharmacology and experimental therapeutics, 300(2), 647-54","doi":null,"pmid":"11805228","tags":["opioid-peptides","pain"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Phase- and level-specific pain modulation: beta-endorphin supraspinal/early phase; enkephalins spinal/late phase; dynorphin both levels/both phases — the most detailed mapping of endogenous opioid pain control organization.","whyItMatters":"This is the most comprehensive mapping of which opioid peptide does what, where, for which type of pain. It provides a complete blueprint for targeted analgesic development.","specificNumbers":"","methodology":"Animal study using ICV and intrathecal injection of selective opioid antisera and receptor antagonists in mice before formalin testing. Both early (acute) and late (inflammatory) pain phases measured at both supraspinal and spinal levels.","limitations":"Mouse formalin test model. Antibody specificity and completeness of blocking are limitations. Acute test may not predict chronic pain organization."},{"rthcId":"RPEP-00785","title":"Chalifour 2003 Aggregation Inhibitor Peptide Abeta","authors":"","year":2003,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00786","title":"Synthetic peptides in the diagnosis of HIV infection.","authors":"Alcaro, Maria Claudia; Peroni, Elisa; Rovero, Paolo; Papini, Anna Maria","year":2003,"journal":"Current protein & peptide science, 4(4), 285-90","doi":null,"pmid":"14529535","tags":[],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Synthetic peptides designed to mimic HIV viral proteins proved sufficiently sensitive and specific for diagnosing HIV infection through ELISA (enzyme-linked immunosorbent assay) tests. These peptide-based diagnostics could reliably detect HIV-specific antibodies in AIDS patients and — importantly — could distinguish between HIV-1 and HIV-2 infections, as well as differentiate between various HIV subtypes.\n\nThe review catalogues the most important peptide antigens developed for HIV immunodiagnosis, showing how synthetic peptides derived from key viral epitopes became practical tools for serological testing.","whyItMatters":"HIV testing is one of the most consequential applications of peptide technology in public health. Using synthetic peptides instead of whole virus preparations made HIV tests safer to manufacture, more reproducible, and more specific. The ability to distinguish between HIV-1 and HIV-2 — and between subtypes — is clinically important because these viruses respond differently to treatment and have different geographic distributions.","specificNumbers":"Distinguishes HIV-1 from HIV-2 · Differentiates viral subtypes · ELISA-based detection · Sufficient sensitivity and specificity reported","methodology":"This is a review paper that surveys the published literature on synthetic peptides used as antigens in HIV immunodiagnostics. It covers peptide design, epitope selection, ELISA performance, and the ability of peptide-based assays to discriminate between HIV types and subtypes.","limitations":"Published in 2003, this review predates many advances in HIV rapid testing and molecular diagnostics. The abstract doesn't report specific sensitivity and specificity values for the peptide-based assays discussed. HIV diagnostic technology has evolved substantially since publication, with fourth-generation tests and nucleic acid testing now standard."},{"rthcId":"RPEP-00787","title":"Pituitary anatomy and physiology.","authors":"Amar, Arun Paul; Weiss, Martin H","year":2003,"journal":"Neurosurgery clinics of North America, 14(1), 11-23, v","doi":null,"pmid":"12690976","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00788","title":"Effect of Epitalon on biomarkers of aging, life span and spontaneous tumor incidence in female Swiss-derived SHR mice.","authors":"Anisimov, V N; Khavinson, V Kh; Popovich, I G; Zabezhinski, M A; Alimova, I N; Rosenfeld, S V; Zavarzina, N Yu; Semenchenko, A V; Yashin, A I","year":2003,"journal":"Biogerontology, 4(4), 193-202","doi":"10.1023/A:1025114230714","pmid":"12753067","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Subcutaneous Epitalon injections (0.1 µg per mouse, 5 consecutive days per month starting at 3 months of age) in female SHR mice increased both mean and maximum lifespan by 12.3% compared to untreated controls.\n\nThe peptide did not increase total spontaneous tumor incidence but significantly decreased the incidence of malignant lymphomas. Additionally, Epitalon preserved estrous cycle function longer, slowed age-related deterioration of immune parameters, and reduced the frequency of chromosome aberrations in bone marrow cells of old mice.","whyItMatters":"Epitalon is one of the Khavinson peptide bioregulators — short synthetic peptides developed in Russia as potential anti-aging interventions. This study is frequently cited in longevity research because it shows a single, very small peptide simultaneously affecting multiple aging biomarkers: lifespan, cancer incidence, reproductive aging, immune function, and chromosomal stability. If these results translate beyond mice, the implications for aging biology would be significant.","specificNumbers":"","methodology":"Female Swiss-derived SHR mice received subcutaneous injections of Epitalon (Ala-Glu-Asp-Gly) at 0.1 µg per mouse for 5 consecutive days each month, beginning at age 3 months and continuing through life. Controls received no treatment. Outcomes measured included lifespan, spontaneous tumor incidence, estrous cycle function, immune parameters, and chromosome aberration frequency in bone marrow cells.","limitations":"This is a single-lab study from the Khavinson/Anisimov research group, which has not been independently replicated by other laboratories. The SHR mouse strain is specific and may not represent general aging biology. The abstract does not report group sizes, making it difficult to assess statistical power. The extremely low dose (0.1 µg) raises questions about mechanism and bioavailability. No human studies of Epitalon for lifespan extension exist."},{"rthcId":"RPEP-00789","title":"Characterization of the effects of pancreatic polypeptide in the regulation of energy balance.","authors":"Asakawa, Akihiro; Inui, Akio; Yuzuriha, Hideki; Ueno, Naohiko; Katsuura, Goro; Fujimiya, Mineko; Fujino, Masayuki A; Niijima, Akira; Meguid, Michael M; Kasuga, Masato","year":2003,"journal":"Gastroenterology, 124(5), 1325-36","doi":null,"pmid":"12730873","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00790","title":"B-type natriuretic peptide: physiologic role and assay characteristics.","authors":"Azzazy, Hassan M E; Christenson, Robert H","year":2003,"journal":"Heart failure reviews, 8(4), 315-20","doi":null,"pmid":"14574050","tags":["natriuretic-peptides","cardiovascular"],"studyType":"review","evidenceStrength":"strong","keyFinding":"BNP has evolved from a research peptide to an essential clinical tool for heart failure diagnosis, prognosis, screening, and treatment monitoring, with particularly high value in emergency department dyspnea differentiation.","whyItMatters":"BNP testing has transformed emergency cardiac care. A simple blood test that distinguishes heart failure from lung disease in breathless patients saves lives through rapid, accurate diagnosis.","specificNumbers":"","methodology":"Review of BNP physiology, molecular biology, assay characteristics, and clinical applications across heart failure care settings.","limitations":"Review from 2003. BNP assay standardization and cutoff refinement continued after publication. NT-proBNP emerged as a competitor."},{"rthcId":"RPEP-00791","title":"Pancreatic polypeptide reduces appetite and food intake in humans.","authors":"Batterham, R L; Le Roux, C W; Cohen, M A; Park, A J; Ellis, S M; Patterson, M; Frost, G S; Ghatei, M A; Bloom, S R","year":2003,"journal":"The Journal of clinical endocrinology and metabolism, 88(8), 3989-92","doi":null,"pmid":"12915697","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00792","title":"Different effect of antiulcer agents on rat cysteamine-induced duodenal ulcer after sialoadenectomy, but not gastrectomy.","authors":"Bedekovic, Vlado; Mise, Stjepan; Anic, Tomislav; Staresinic, Mario; Gjurasin, Miroslav; Kopljar, Mario; Kalogjera, Livije; Drvis, Petar; Boban Blagaic, Alenka; Batelja, Lovorka; Seiwerth, Sven; Sikiric, Predrag","year":2003,"journal":"European journal of pharmacology, 477(1), 73-80","doi":null,"pmid":"14512101","tags":["bpc-157","gut-healing"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"BPC-157 maintained duodenal ulcer healing after sialoadenectomy while cimetidine and ranitidine lost effectiveness, demonstrating BPC-157's independence from salivary gland-derived protective factors — a unique pharmacological property.","whyItMatters":"Patients with Sjögren's syndrome and other conditions affecting salivary function may not respond to conventional ulcer drugs. BPC-157's saliva-independent healing could benefit these patients.","specificNumbers":"","methodology":"Animal study in rats with cysteamine-induced duodenal ulcers. Three conditions: normal rats, sialoadenectomized rats (no salivary glands), and gastrectomized rats (no stomach). BPC-157 and standard anti-ulcer drugs compared.","limitations":"Rat model. Sialoadenectomy is more complete than clinical salivary dysfunction. The specific salivary factors involved were not identified."},{"rthcId":"RPEP-00793","title":"Abnormal rhythmic oscillations of atrial natriuretic peptide and brain natriuretic peptide in heart failure.","authors":"Bentzen, Hans; Pedersen, Robert S; Pedersen, Henrik B; Nyvad, Ole; Pedersen, Erling B","year":2003,"journal":"Clinical science (London, England : 1979), 104(3), 303-12","doi":null,"pmid":"12605591","tags":["natriuretic-peptides","cardiovascular"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"Heart failure disrupted the normal pulsatile secretion patterns of both ANP and BNP, with BNP rhythm abnormalities correlating with disease severity — adding temporal pattern analysis to biomarker diagnostics.","whyItMatters":"Measuring just the level of BNP may miss important information contained in the secretion pattern. Rhythm analysis could distinguish different stages or types of heart failure that have similar average BNP levels.","specificNumbers":"","methodology":"Clinical study with frequent blood sampling (every 10-20 minutes) in chronic heart failure patients and controls to characterize ANP and BNP pulsatile secretion patterns using pulse analysis algorithms.","limitations":"Intensive sampling protocol (impractical for routine clinical use). Small patient numbers inherent to frequent sampling studies. The clinical utility of rhythm analysis over simple levels is unproven."},{"rthcId":"RPEP-00794","title":"Prognostic power of neurohumoral parameters in chronic heart failure depends on clinical stage and observation period.","authors":"Berger, Rudolf; Strecker, Karin; Huelsmann, Martin; Moser, Petra; Frey, Bernhard; Bojic, Anja; Stanek, Brigitte; Pacher, Richard","year":2003,"journal":"The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation, 22(9), 1037-45","doi":null,"pmid":"12957614","tags":["natriuretic-peptides","cardiovascular"],"studyType":"cohort","evidenceStrength":"strong","keyFinding":"BNP best predicted short-term outcomes in mild-moderate heart failure, while endothelin was more prognostic in advanced heart failure and over longer follow-up, demonstrating stage- and time-dependent prognostic value of neurohormonal biomarkers.","whyItMatters":"Choosing the right biomarker for risk prediction depends on context. BNP is best for early-stage risk assessment, while endothelin adds value in advanced disease — precision prognosis.","specificNumbers":"","methodology":"Prospective cohort study measuring BNP, NT-proBNP, ANP, and endothelin in CHF patients across NYHA classes II-IV. Prognostic power assessed for different disease stages and follow-up periods.","limitations":"Observational cohort. Specific cutoffs and time horizons may vary between populations. Multi-marker panels add cost and complexity."},{"rthcId":"RPEP-00795","title":"Purification and quantification of opioid peptides in bone and joint tissues--a methodological study in the rat.","authors":"Bergström, J; Ahmed, M; Kreicbergs, A; Nylander, I","year":2003,"journal":"Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 21(3), 465-9","doi":null,"pmid":"12706019","tags":["opioid-peptides","bone-joint","pain"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Met-enkephalin-Arg-Phe and dynorphin B were quantified in rat cortical bone, periosteum, bone marrow, joint cartilage, and synovial membrane, establishing a local opioid peptide system in musculoskeletal tissues.","whyItMatters":"A local opioid system in bones and joints could be targeted for pain relief directly at the site of injury or arthritis, potentially providing analgesia without central nervous system side effects.","specificNumbers":"","methodology":"Methodological study developing tissue extraction and purification techniques for opioid peptide measurement in bone and joint specimens. RIA quantification across multiple musculoskeletal tissues.","limitations":"Methodological study focused on detection rather than function. The physiological role of musculoskeletal opioid peptides was not determined. Rat tissues may differ from human."},{"rthcId":"RPEP-00796","title":"Novel antibiotics: macrocyclic peptides designed to trap Holliday junctions.","authors":"Bolla, Megan L; Azevedo, Enrique V; Smith, Jason M; Taylor, Rachel E; Ranjit, Dev K; Segall, Anca M; McAlpine, Shelli R","year":2003,"journal":"Organic letters, 5(2), 109-12","doi":null,"pmid":"12529117","tags":["cyclic-peptides","antimicrobial-peptides","infection","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Macrocyclic peptides designed to bind Holliday DNA junctions showed antibacterial activity, validating a completely novel antibiotic mechanism targeting bacterial DNA repair/recombination.","whyItMatters":"A completely new antibiotic mechanism — targeting DNA junctions — gives bacteria no pre-existing resistance. Novel mechanisms are desperately needed as existing antibiotic classes fail.","specificNumbers":"","methodology":"In-vitro study. Eight macrocyclic peptides designed computationally to bind Holliday junction DNA structures. Synthesized and tested for antibacterial activity against bacterial cultures.","limitations":"Short abstract with limited potency data. In-vivo efficacy unknown. Selectivity for bacterial versus human DNA junctions needs confirmation."},{"rthcId":"RPEP-00797","title":"Central and peripheral activities of ghrelin, a ligand of the growth hormone secretagogue receptor.","authors":"Bona, G; Bellone, S","year":2003,"journal":"Panminerva medica, 45(3), 197-201","doi":null,"pmid":"14618118","tags":["ghrp","hormone-optimization","cardiovascular","gut-healing"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Ghrelin displays integrated central (GH, appetite, neuroprotection) and peripheral (cardiac, adipose, gastric) activities through widespread GHS-R distribution, functioning as a systemic metabolic coordinator rather than a single-function hormone.","whyItMatters":"Understanding ghrelin's full activity profile is essential for drug development — every ghrelin-targeting drug will affect multiple body systems.","specificNumbers":"","methodology":"Comprehensive review of all ghrelin central and peripheral activities with synthesis of therapeutic implications.","limitations":"Review from 2003 when some activities were still being characterized. Some proposed therapeutic implications were speculative."},{"rthcId":"RPEP-00798","title":"Cyclooxygenase-2 induction by bradykinin in human pulmonary artery smooth muscle cells is mediated by the cyclic AMP response element through a novel autocrine loop involving endogenous prostaglandin E2, E-prostanoid 2 (EP2), and EP4 receptors.","authors":"Bradbury, Dawn A; Newton, Robert; Zhu, Yong M; El-Haroun, Hala; Corbett, Lisa; Knox, Alan J","year":2003,"journal":"The Journal of biological chemistry, 278(50), 49954-64","doi":null,"pmid":"14517215","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00799","title":"Endocrine and non-endocrine actions of ghrelin.","authors":"Broglio, Fabio; Gottero, Cristina; Arvat, Emanuela; Ghigo, Ezio","year":2003,"journal":"Hormone research, 59(3), 109-17","doi":null,"pmid":"12637790","tags":["ghrp","hormone-optimization","cardiovascular","immune-function"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Ghrelin's comprehensive activity profile includes GH/prolactin/cortisol release, appetite stimulation, adiposity, cardiovascular protection, and immune modulation, with multi-tissue production supporting both endocrine and local paracrine functions.","whyItMatters":"The most complete ghrelin activity overview available at the time, essential for understanding the full scope of what ghrelin-targeting drugs will affect.","specificNumbers":"","methodology":"Comprehensive review integrating all published ghrelin endocrine, metabolic, cardiovascular, and immunological activities with tissue distribution data.","limitations":"Review from 2003. Some proposed activities were still being characterized. The relative importance of each activity for clinical applications was debated."},{"rthcId":"RPEP-00800","title":"Activation of delta- and kappa-opioid receptors by opioid peptides protects cardiomyocytes via KATP channels.","authors":"Cao, Zhiping; Liu, Lijuan; Van Winkle, Donna M","year":2003,"journal":"American journal of physiology. Heart and circulatory physiology, 285(3), H1032-9","doi":null,"pmid":"12730057","tags":["opioid-peptides","cardiovascular"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Delta-opioid (met-enkephalin) and kappa-opioid (dynorphin A) receptor activation protected cardiomyocytes from simulated ischemia through KATP channel opening, confirming the opioid-KATP cardioprotection pathway.","whyItMatters":"Understanding exactly how opioid peptides protect the heart enables development of cardiac-specific opioid drugs that prevent heart attack damage without affecting the brain.","specificNumbers":"","methodology":"In-vitro study using freshly isolated adult rabbit cardiomyocytes. Simulated ischemia with selective opioid agonists, receptor antagonists, and KATP channel blockers to dissect the protective mechanism.","limitations":"Isolated cell model. Cardiomyocyte protection in vitro may not predict whole-heart or in-vivo protection. The interaction between delta and kappa pathways was not fully explored."},{"rthcId":"RPEP-00801","title":"Pyrazolinone-piperidine dipeptide growth hormone secretagogues (GHSs). Discovery of capromorelin.","authors":"Carpino, Philip A; Lefker, Bruce A; Toler, Steven M; Pan, Lydia C; Hadcock, John R; Cook, Ewell R; DiBrino, Joseph N; Campeta, Anthony M; DeNinno, Shari L; Chidsey-Frink, Kristin L; Hada, William A; Inthavongsay, John; Mangano, F Michael; Mullins, Michelle A; Nickerson, David F; Ng, Oicheng; Pirie, Christine M; Ragan, John A; Rose, Colin R; Tess, David A; Wright, Ann S; Yu, Li; Zawistoski, Michael P; DaSilva-Jardine, Paul A; Wilson, Theresa C; Thompson, David D","year":2003,"journal":"Bioorganic & medicinal chemistry, 11(4), 581-90","doi":null,"pmid":"12538023","tags":["ghrp","peptide-design","hormone-optimization","bioavailability"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Capromorelin showed potent GHS-R binding (Ki=7 nM), oral GH-releasing activity in rats, 60% oral bioavailability in dogs, and IGF-1 elevation with repeated dosing, emerging as a clinical development candidate.","whyItMatters":"An oral GH secretagogue with 60% bioavailability is exceptional. This drug-like profile makes oral GH therapy practical, potentially replacing GH injections.","specificNumbers":"","methodology":"Preclinical study with GHS-R binding assays, in-vitro pituitary cell GH release, in-vivo GH/IGF-1 measurement in rats, and pharmacokinetic analysis in dogs.","limitations":"Preclinical data only. Dog bioavailability may not predict human PK. Long-term safety not assessed."},{"rthcId":"RPEP-00802","title":"In patients with severe systolic dysfunction, only brain natriuretic peptide is related to diastolic restrictive pattern.","authors":"Catuzzo, Bruna; Ciancamerla, Francesca; Bobbio, Marco; Longo, Marcella; Trevi, Gian Paolo","year":2003,"journal":"Journal of cardiac failure, 9(4), 303-10","doi":null,"pmid":"13680551","tags":["natriuretic-peptides","cardiovascular"],"studyType":"cross-sectional","evidenceStrength":"moderate","keyFinding":"Among BNP, ANP, catecholamines, renin, and aldosterone, only BNP correlated with the restrictive diastolic filling pattern in severe systolic dysfunction — the most specific biomarker for this ominous prognostic sign.","whyItMatters":"Restrictive filling predicts death in severe heart failure. Having a blood test (BNP) that specifically identifies this pattern enables risk stratification without requiring detailed echocardiography.","specificNumbers":"","methodology":"Cross-sectional study in patients with severe systolic dysfunction (LVEF ≤30%). Echocardiographic diastolic filling patterns classified. BNP, ANP, catecholamines, renin, and aldosterone measured.","limitations":"Cross-sectional design. Specific BNP cutoff for restrictive filling not established. Sample size and echocardiographic classification methods limited."},{"rthcId":"RPEP-00803","title":"A pilot study of the safety and efficacy of thymosin alpha 1 in augmenting immune reconstitution in HIV-infected patients with low CD4 counts taking highly active antiretroviral therapy.","authors":"Chadwick, D; Pido-Lopez, J; Pires, A; Imami, N; Gotch, F; Villacian, J S; Ravindran, S; Paton, N I","year":2003,"journal":"Clinical and experimental immunology, 134(3), 477-81","doi":null,"pmid":"14632754","tags":["thymosin-alpha-1","immune-function","infection","clinical-trials"],"studyType":"RCT","evidenceStrength":"moderate","keyFinding":"Thymosin alpha-1 + HAART improved CD4+ T-cell recovery in HIV patients with suboptimal immune reconstitution, with acceptable safety, demonstrating efficacy as an immune adjuvant for HIV treatment non-responders.","whyItMatters":"Up to 30% of HIV patients on HAART don't recover adequate CD4 counts, remaining vulnerable to opportunistic infections. An immune booster that addresses this gap could save lives in this large subpopulation.","specificNumbers":"","methodology":"Phase II randomized, controlled, open-label trial in HIV patients on HAART with suboptimal CD4 recovery. Thymosin alpha-1 added to HAART versus HAART alone. CD4 counts, viral load, and safety monitored.","limitations":"Phase II pilot study; open-label design introduces bias. Small sample. Long-term durability of CD4 improvement not established."},{"rthcId":"RPEP-00804","title":"Acute effects of PYY3-36 on food intake and hypothalamic neuropeptide expression in the mouse.","authors":"Challis, B G; Pinnock, S B; Coll, A P; Carter, R N; Dickson, S L; O'Rahilly, S","year":2003,"journal":"Biochemical and biophysical research communications, 311(4), 915-9","doi":null,"pmid":"14623268","tags":["neuropeptides","weight-loss"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Peripheral PYY3-36 acutely suppressed food intake and altered hypothalamic neuropeptide expression (decreased NPY, increased POMC) in mice, confirming it as a gut-derived satiety signal that modulates central appetite gene programs.","whyItMatters":"Understanding how gut satiety peptides change brain hunger genes enables development of more effective appetite-suppressing drugs that work at the gene expression level.","specificNumbers":"","methodology":"Animal study. PYY3-36 administered peripherally to mice. Food intake measured. Hypothalamic neuropeptide gene expression (NPY, POMC, AgRP, CART) analyzed by in situ hybridization.","limitations":"Mouse study with acute PYY3-36 administration. Chronic effects may differ. Whether the gene expression changes persist is unknown."},{"rthcId":"RPEP-00805","title":"Antibacterial activity of short hydrophobic and basic-rich peptides.","authors":"Chen, Po-Wen; Shyu, Ching-Ling; Mao, Frank C","year":2003,"journal":"American journal of veterinary research, 64(9), 1088-92","doi":null,"pmid":"13677384","tags":["antimicrobial-peptides","infection","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Five synthetic 5-amino-acid peptides designed from lactoferricin's principles of lipophilic bulk and cationic charge showed potent broad-spectrum antibacterial activity, demonstrating ultra-short peptide antibiotics are viable.","whyItMatters":"Shorter peptides are cheaper to make, more stable, and easier to formulate. Ultra-short antimicrobial peptides could be the most practical peptide antibiotics for clinical development.","specificNumbers":"","methodology":"In-vitro antimicrobial study. Five 5-amino-acid peptides designed from lactoferricin structure-activity principles. Tested against panels of gram-positive and gram-negative bacteria by MIC determination.","limitations":"In-vitro activity only. Ultra-short peptides may have different pharmacokinetics and toxicity profiles than longer antimicrobial peptides. Hemolytic activity needs assessment."},{"rthcId":"RPEP-00806","title":"Secretin, 100 years later.","authors":"Chey, William Y; Chang, Ta-Min","year":2003,"journal":"Journal of gastroenterology, 38(11), 1025-35","doi":null,"pmid":"14673718","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00807","title":"Gastric pacing for morbid obesity: plasma levels of gastrointestinal peptides and leptin.","authors":"Cigaina, Valerio; Hirschberg, Angelica L","year":2003,"journal":"Obesity research, 11(12), 1456-62","doi":null,"pmid":"14694209","tags":["glp-1","weight-loss","neuropeptides"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"Gastric pacing in morbidly obese patients altered circulating CCK, somatostatin, and leptin levels, providing a neuroendocrine mechanism for the satiety and weight loss effects of this device.","whyItMatters":"Understanding that gastric pacing works through hormones, not just mechanics, opens the door to optimizing the electrical parameters for maximal appetite-suppressing peptide release.","specificNumbers":"","methodology":"Clinical trial measuring plasma gut peptides (CCK, somatostatin, GLP-1, PYY) and leptin in morbidly obese patients before and during gastric electrical pacing treatment.","limitations":"Small clinical study. Cause-effect relationship between peptide changes and weight loss not definitively established. The specific pacing parameters affecting each peptide not characterized."},{"rthcId":"RPEP-00808","title":"Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54.","authors":"de Roux, Nicolas; Genin, Emmanuelle; Carel, Jean-Claude; Matsuda, Fumihiko; Chaussain, Jean-Louis; Milgrom, Edwin","year":2003,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 100(19), 10972-6","doi":null,"pmid":"12944565","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00809","title":"Targeting the ghrelin receptor: orally active GHS and cortistatin analogs.","authors":"Deghenghi, Romano; Broglio, Fabio; Papotti, Mauro; Muccioli, Giampiero; Ghigo, Ezio","year":2003,"journal":"Endocrine, 22(1), 13-8","doi":null,"pmid":"14610294","tags":["ghrp","peptide-design","hormone-optimization","bioavailability"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Orally active GH secretagogues and cortistatin (a somatostatin-related peptide) both target the ghrelin receptor, expanding the receptor's known ligand repertoire and therapeutic targeting possibilities.","whyItMatters":"The ghrelin receptor integrates signals from multiple peptide families. Understanding this broader ligand landscape improves drug design and predicts clinical effects more accurately.","specificNumbers":"","methodology":"Review of oral GH secretagogue development (peptide and non-peptide) and the emerging pharmacology of cortistatin-GHS-R interaction.","limitations":"Review from 2003. The clinical significance of cortistatin-GHS-R interaction was still being explored."},{"rthcId":"RPEP-00810","title":"Interaction of the growth hormone-releasing peptides ghrelin and growth hormone-releasing peptide-6 with the motilin receptor in the rabbit gastric antrum.","authors":"Depoortere, Inge; Thijs, Theo; Thielemans, Leen; Robberecht, Patrick; Peeters, Theo L","year":2003,"journal":"The Journal of pharmacology and experimental therapeutics, 305(2), 660-7","doi":null,"pmid":"12606621","tags":["ghrp","gut-healing","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Bidirectional cross-reactivity between ghrelin/GHRP-6 and the motilin receptor was demonstrated: ghrelin activated the motilin receptor and motilin activated GHS-R, linking GH regulation and gut motility at the receptor level.","whyItMatters":"This cross-reactivity explains why GH secretagogues cause gut side effects (nausea, motility changes) and suggests motilin receptor drugs could affect GH release.","specificNumbers":"","methodology":"In-vitro receptor pharmacology. Ghrelin, GHRP-6, and motilin tested on cells expressing either GHS-R or motilin receptor. Binding and functional activation measured for both ligand-receptor combinations.","limitations":"In-vitro cross-reactivity. The physiological significance of motilin-GHS-R activation at endogenous concentrations is uncertain."},{"rthcId":"RPEP-00811","title":"Heparin-interacting sites of bovine lactoferrin are involved in anti-adenovirus activity.","authors":"Di Biase, Assunta Maria; Pietrantoni, Agostina; Tinari, Antonella; Siciliano, Rosa; Valenti, Piera; Antonini, Giovanni; Seganti, Lucilla; Superti, Fabiana","year":2003,"journal":"Journal of medical virology, 69(4), 495-502","doi":null,"pmid":"12601757","tags":["antimicrobial-peptides","infection"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Lactoferrin's anti-adenovirus activity was mediated through its heparin-interacting domains, which compete with viral attachment to cell surface heparan sulfate — a mechanism explaining its broad antiviral spectrum against heparan sulfate-binding viruses.","whyItMatters":"Many important viruses (adenovirus, herpes, HPV, some coronaviruses) use heparan sulfate for cell entry. A natural protein that blocks this universal attachment mechanism has broad antiviral potential.","specificNumbers":"","methodology":"In-vitro antiviral study. Bovine lactoferrin and domain-modified variants tested against adenovirus infection. Heparin competition and binding site mutation experiments to determine the mechanism.","limitations":"In-vitro mechanism study with adenovirus. The concentrations needed for in-vivo antiviral protection are uncertain."},{"rthcId":"RPEP-00812","title":"The heptapeptide SEMAX stimulates BDNF expression in different areas of the rat brain in vivo.","authors":"Dolotov, O V; Seredenina, T S; Levitskaya, N G; Kamensky, A A; Andreeva, L A; Alfeeva, L Yu; Nagaev, I Yu; Zolotarev, Yu A; Grivennikov, I A; Engele, Yu; Myasoedov, N F","year":2003,"journal":"Doklady biological sciences : proceedings of the Academy of Sciences of the USSR, Biological sciences sections, 391, 292-5","doi":null,"pmid":"14556513","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00813","title":"Peripheral signals in the control of satiety and hunger.","authors":"Drazen, Deborah L; Woods, Stephen C","year":2003,"journal":"Current opinion in clinical nutrition and metabolic care, 6(6), 621-9","doi":null,"pmid":"14557791","tags":["neuropeptides","weight-loss","glp-1"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Satiety is controlled by a two-tier peripheral signaling system: short-term gut peptides (CCK, GLP-1, PYY, ghrelin, oxyntomodulin) for meal control and long-term adiposity signals (leptin, insulin) for body weight regulation, integrated by brainstem and hypothalamic circuits.","whyItMatters":"This review describes the complete signaling architecture that modern obesity drugs target. GLP-1 agonists (semaglutide) work through one of the many pathways described here.","specificNumbers":"","methodology":"Comprehensive review of all peripheral satiety and hunger signals, their receptors, neural pathways, and integration in central appetite circuits.","limitations":"Review from 2003. Some signals described were still being characterized. The relative importance of each signal for human obesity treatment was debated."},{"rthcId":"RPEP-00814","title":"Enhanced antitumour activity of 15-residue bovine lactoferricin derivatives containing bulky aromatic amino acids and lipophilic N-terminal modifications.","authors":"Eliassen, Liv Tone; Haug, Bengt Erik; Berge, Gerd; Rekdal, Oystein","year":2003,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 9(8), 510-7","doi":null,"pmid":"12952392","tags":["antimicrobial-peptides","cancer"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Bulky aromatic amino acid substitutions and lipophilic modifications enhanced bovine lactoferricin antitumor activity in a 15-residue fragment, with tryptophan residues identified as essential for cancer cell killing through membrane-disrupting mechanisms.","whyItMatters":"Optimizing natural anticancer peptides could yield drugs that kill cancer cells through membrane disruption — a mechanism that cancer cells can't easily resist through genetic mutation.","specificNumbers":"","methodology":"In-vitro SAR study. Amino acid substitutions and lipophilic modifications of LFB(17-31) tested against cancer cell lines. Tryptophan importance confirmed by selective replacement. Membrane disruption mechanism characterized.","limitations":"In-vitro cancer cell activity. Selectivity for cancer versus normal cells needs assessment. In-vivo antitumor efficacy not tested."},{"rthcId":"RPEP-00815","title":"Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene.","authors":"Farooqi, I Sadaf; Keogh, Julia M; Yeo, Giles S H; Lank, Emma J; Cheetham, Tim; O'Rahilly, Stephen","year":2003,"journal":"The New England journal of medicine, 348(12), 1085-95","doi":null,"pmid":"12646665","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00816","title":"Epitope prediction algorithms for peptide-based vaccine design.","authors":"Florea, Liliana; Halldórsson, Bjarni; Kohlbacher, Oliver; Schwartz, Russell; Hoffman, Stephen; Istrail, Sorin","year":2003,"journal":"Proceedings. IEEE Computer Society Bioinformatics Conference, 2, 17-26","doi":null,"pmid":"16826643","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00817","title":"Effect of ghrelin and synthetic growth hormone secretagogues in normal and ischemic rat heart.","authors":"Frascarelli, Sabina; Ghelardoni, Sandra; Ronca-Testoni, Simonetta; Zucchi, Riccardo","year":2003,"journal":"Basic research in cardiology, 98(6), 401-5","doi":null,"pmid":"14556085","tags":["ghrp","mk-677","cardiovascular"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Ghrelin, hexarelin, and EP-80317 improved cardiac contractile recovery after ischemia in isolated rat hearts, with effects on coronary perfusion pressure, while MK-677 showed less cardioprotection — suggesting peptide GHS are preferred cardiac protectants.","whyItMatters":"Demonstrating that peptide GH secretagogues are better cardioprotectants than non-peptide MK-677 guides drug selection for cardiac applications and suggests a peptide-preferring cardiac receptor.","specificNumbers":"","methodology":"In-vitro isolated rat heart (Langendorff) study. Ghrelin, hexarelin, EP-80317, and MK-677 tested before or during ischemia-reperfusion. Cardiac contractile function and coronary perfusion pressure measured.","limitations":"Isolated rat heart model. The specific cardiac receptor mediating protection was not definitively identified. Short-term ischemia protocol."},{"rthcId":"RPEP-00818","title":"Serum ratio of heart-type fatty acid-binding protein to myoglobin. A novel marker of cardiac damage and volume overload in hemodialysis patients.","authors":"Furuhashi, Masato; Ura, Nobuyuki; Hasegawa, Koichi; Yoshida, Hideaki; Tsuchihashi, Kazufumi; Nakata, Tomoaki; Shimamoto, Kaxuaki","year":2003,"journal":"Nephron. Clinical practice, 93(2), C69-74","doi":null,"pmid":"12616033","tags":["natriuretic-peptides","cardiovascular","kidney"],"studyType":"cross-sectional","evidenceStrength":"moderate","keyFinding":"The hFABP/myoglobin ratio combined with BNP improved detection of cardiac damage and volume overload in dialysis patients, providing a multi-marker approach that overcomes renal clearance confounding of individual markers.","whyItMatters":"Single biomarkers have limitations in kidney failure patients. Multi-marker approaches that account for renal confounding improve diagnostic accuracy for this extremely high-risk population.","specificNumbers":"","methodology":"Cross-sectional study in dialysis patients. hFABP, myoglobin, BNP, ANP, and cardiac function parameters measured. The hFABP/myoglobin ratio developed to normalize for renal clearance effects.","limitations":"Cross-sectional design. The specific hFABP/myoglobin ratio cutoffs need validation. Dialysis timing affects all markers."},{"rthcId":"RPEP-00819","title":"Thymosin alpha(1) in combination with cytokines and chemotherapy for the treatment of cancer.","authors":"Garaci, Enrico; Pica, Francesca; Sinibaldi-Vallebona, Paola; Pierimarchi, Pasquale; Mastino, Antonio; Matteucci, Claudia; Rasi, Guido","year":2003,"journal":"International immunopharmacology, 3(8), 1145-50","doi":null,"pmid":"12860169","tags":["thymosin-alpha-1","cancer","immune-function","clinical-trials"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Thymosin alpha-1 combined with low-dose cytokines and chemotherapy produced superior anti-tumor effects across experimental and human cancers, validating the triple-combination immunotherapy approach.","whyItMatters":"Cancer immunotherapy combinations are the future of oncology. Thymosin alpha-1 as an affordable, well-tolerated immune enhancer could be added to many existing regimens.","specificNumbers":"","methodology":"Review of preclinical and clinical studies combining thymosin alpha-1 with cytokines (IFN-alpha, IL-2) and chemotherapy across multiple cancer types.","limitations":"Review with varying evidence quality across cancer types. Head-to-head comparisons with modern immunotherapies were not available."},{"rthcId":"RPEP-00820","title":"Dissection of the anti-inflammatory effect of the core and C-terminal (KPV) alpha-melanocyte-stimulating hormone peptides.","authors":"Getting, Stephen J; Schiöth, Helgi B; Perretti, Mauro","year":2003,"journal":"The Journal of pharmacology and experimental therapeutics, 306(2), 631-7","doi":null,"pmid":"12750433","tags":["kpv","inflammation"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"KPV (alpha-MSH 11-13) reduced crystal-induced peritonitis as effectively as full-length alpha-MSH via systemic administration, with melanocortin receptor-independent anti-inflammatory activity at the inflammation site.","whyItMatters":"A 3-amino-acid peptide with full anti-inflammatory activity is incredibly practical for drug development — tiny, cheap to produce, and potentially orally bioavailable.","specificNumbers":"","methodology":"Animal study using crystal-induced peritonitis model. Systemic administration of alpha-MSH, KPV (11-13), core peptide HFRW (6-9), and fragments. Inflammatory cell infiltration and cytokine production measured.","limitations":"Mouse peritonitis model. The melanocortin receptor-independent mechanism needs further characterization. Systemic dosing — local delivery effects not compared."},{"rthcId":"RPEP-00821","title":"Immunodeficiency and cancer: prospects for correction.","authors":"Hadden, John W","year":2003,"journal":"International immunopharmacology, 3(8), 1061-71","doi":null,"pmid":"12860163","tags":["thymosin-alpha-1","cancer","immune-function"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Cellular immunodeficiency precedes and promotes cancer across multiple tumor types, and immunological correction with thymosin alpha-1 and cytokines alongside conventional therapy consistently improves patient outcomes.","whyItMatters":"If immunodeficiency drives cancer and correcting it improves outcomes, then immune assessment should be as routine as staging. Thymosin alpha-1 offers a practical tool for immune correction.","specificNumbers":"","methodology":"Comprehensive review of immunodeficiency in head/neck, lung, esophageal, and breast cancers, covering evidence for immune assessment and correction with biological response modifiers.","limitations":"Review from 2003. Some immunological assessments described were not standardized. The degree of improvement from immune correction varied across studies."},{"rthcId":"RPEP-00822","title":"Casein and whey exert different effects on plasma amino acid profiles, gastrointestinal hormone secretion and appetite.","authors":"Hall, W L; Millward, D J; Long, S J; Morgan, L M","year":2003,"journal":"The British journal of nutrition, 89(2), 239-48","doi":null,"pmid":"12575908","tags":["bioactive-food-peptides","weight-loss","opioid-peptides"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"Whey protein produced greater short-term satiety than casein in humans, with faster amino acid absorption, higher plasma amino acid peaks, and different gastrointestinal hormone (CCK, GLP-1) profiles.","whyItMatters":"Choosing the right protein source is a practical, accessible weight management strategy. This study provides the scientific basis for recommending whey over casein for appetite control.","specificNumbers":"","methodology":"Controlled clinical trial comparing casein and whey protein meals in humans. Plasma amino acids, gut hormones (CCK, GLP-1, GIP), insulin, and subjective appetite ratings measured over hours.","limitations":"Short-term satiety measurement. Single-meal study. Chronic effects of protein type on body weight not assessed."},{"rthcId":"RPEP-00823","title":"The thymosins. Prothymosin alpha, parathymosin, and beta-thymosins: structure and function.","authors":"Hannappel, Ewald; Huff, Thomas","year":2003,"journal":"Vitamins and hormones, 66, 257-96","doi":null,"pmid":"12852257","tags":["thymosin-alpha-1","immune-function","cancer"],"studyType":"review","evidenceStrength":"strong","keyFinding":"The thymosin family comprises functionally distinct members: prothymosin alpha (gene regulation), thymosin alpha-1 (immune modulation), parathymosin (chromatin), and beta-thymosins (cytoskeleton/wound healing) — each with unique therapeutic potential.","whyItMatters":"Understanding the complete thymosin family reveals that the thymus produces not just immune peptides but regulators of gene expression, cell structure, and wound healing — a broader therapeutic toolkit than assumed.","specificNumbers":"","methodology":"Comprehensive review covering thymosin discovery, structural characterization, biological functions, and clinical development across all family members.","limitations":"Comprehensive but high-level review. Some proposed functions were still being validated. The relationships between family members were not fully characterized."},{"rthcId":"RPEP-00824","title":"Expression of LL-37 by human gastric epithelial cells as a potential host defense mechanism against Helicobacter pylori.","authors":"Hase, Koji; Murakami, Masamoto; Iimura, Mitsutoshi; Cole, Sheri P; Horibe, Yoshimune; Ohtake, Takaaki; Obonyo, Marygorret; Gallo, Richard L; Eckmann, Lars; Kagnoff, Martin F","year":2003,"journal":"Gastroenterology, 125(6), 1613-25","doi":null,"pmid":"14724813","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00825","title":"Mechanism of lipid bilayer disruption by the human antimicrobial peptide, LL-37.","authors":"Henzler Wildman, Katherine A; Lee, Dong-Kuk; Ramamoorthy, A","year":2003,"journal":"Biochemistry, 42(21), 6545-58","doi":null,"pmid":"12767238","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00826","title":"Melanocortin-4 receptor gene: case-control study and transmission disequilibrium test confirm that functionally relevant mutations are compatible with a major gene effect for extreme obesity.","authors":"Hinney, Anke; Hohmann, Sarah; Geller, Frank; Vogel, Constanze; Hess, Claudia; Wermter, Anne-Kathrin; Brokamp, Britta; Goldschmidt, Hanspeter; Siegfried, Wolfgang; Remschmidt, Helmut; Schäfer, Helmut; Gudermann, Thomas; Hebebrand, Johannes","year":2003,"journal":"The Journal of clinical endocrinology and metabolism, 88(9), 4258-67","doi":null,"pmid":"12970296","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00827","title":"Neuropeptide systems as novel therapeutic targets for depression and anxiety disorders.","authors":"Holmes, Andrew; Heilig, Markus; Rupniak, Nadia M J; Steckler, Thomas; Griebel, Guy","year":2003,"journal":"Trends in pharmacological sciences, 24(11), 580-8","doi":null,"pmid":"14607081","tags":["neuropeptides","anxiety-mood","peptide-design"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Multiple neuropeptide systems (CRF, NPY, substance P/NK1, galanin, vasopressin, nociceptin) offer novel antidepressant and anxiolytic targets with mechanisms fundamentally different from monoamine-based drugs.","whyItMatters":"Depression and anxiety affect hundreds of millions worldwide, and current drugs work for only ~60% of patients. Neuropeptide-targeted drugs could help the treatment-resistant remainder.","specificNumbers":"","methodology":"Comprehensive review of neuropeptide targets for depression and anxiety, covering CRF receptors, NPY, substance P/NK1, galanin, vasopressin V1b, and nociceptin/NOP, with preclinical and clinical evidence.","limitations":"Review from 2003. Several neuropeptide drug candidates have since had mixed clinical results (notably NK1 antagonists). Translation from animal models to human efficacy remains challenging."},{"rthcId":"RPEP-00828","title":"Ghrelin as a potential anti-obesity target.","authors":"Horvath, Tamas L; Castañeda, Tamara; Tang-Christensen, Mads; Pagotto, Uberto; Tschöp, Matthias H","year":2003,"journal":"Current pharmaceutical design, 9(17), 1383-95","doi":null,"pmid":"12769730","tags":["ghrp","weight-loss","hormone-optimization"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Ghrelin's unique status as the only circulating appetite-promoting hormone, combined with evidence from knockout and antibody studies, makes it a rational anti-obesity drug target for reducing hunger and fat accumulation.","whyItMatters":"Obesity is the largest public health crisis globally. Targeting the body's one hunger hormone is the most direct pharmacological approach to reducing appetite at its source.","specificNumbers":"","methodology":"Review of evidence supporting ghrelin antagonism for obesity treatment, covering knockout mice, immunoneutralization studies, ghrelin physiology, and therapeutic development challenges.","limitations":"Review from 2003. Ghrelin antagonists have had limited clinical success partly due to appetite system redundancy. GLP-1 agonists have proven more clinically effective."},{"rthcId":"RPEP-00829","title":"Identification of a novel Na+- and Cl--coupled transport system for endogenous opioid peptides in retinal pigment epithelium and induction of the transport system by HIV-1 Tat.","authors":"Hu, Huankai; Miyauchi, Seiji; Bridges, Christy C; Smith, Sylvia B; Ganapathy, Vadivel","year":2003,"journal":"The Biochemical journal, 375(Pt 1), 17-22","doi":null,"pmid":"12924983","tags":["opioid-peptides","eye-health","peptide-delivery"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"A novel Na+/Cl--coupled opioid peptide transport system was identified in retinal pigment epithelial cells, enabling active regulation of local opioid peptide concentrations at the blood-retinal barrier.","whyItMatters":"The eye has its own opioid regulation system. Understanding this could lead to eye-specific opioid therapies for pain (post-surgical), inflammation (uveitis), and retinal diseases.","specificNumbers":"","methodology":"In-vitro transport study using cultured human RPE cells. Opioid peptide uptake kinetics measured with Na+ and Cl- dependency, substrate specificity, and pharmacological characterization.","limitations":"In-vitro RPE cell culture. The physiological role of opioid peptide transport in intact retina needs in-vivo confirmation. The specific transporter protein was not molecularly identified."},{"rthcId":"RPEP-00830","title":"Structure-based design of a macrocyclic inhibitor for peptide deformylase.","authors":"Hu, Xubo; Nguyen, Kiet T; Verlinde, Christophe L M J; Hol, Wim G J; Pei, Dehua","year":2003,"journal":"Journal of medicinal chemistry, 46(18), 3771-4","doi":null,"pmid":"12930137","tags":["cyclic-peptides","antimicrobial-peptides","infection","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"A structure-based macrocyclic peptide deformylase inhibitor showed potent enzyme inhibition with a novel antibiotic mechanism targeting an essential bacterial enzyme absent in humans.","whyItMatters":"Peptide deformylase is a validated antibiotic target with no human equivalent, ensuring selectivity. Macrocyclic inhibitors achieve potent binding through conformational restriction.","specificNumbers":"","methodology":"Structure-based drug design using crystal structure of peptide deformylase. Macrocyclic inhibitor designed by cross-linking P1' and P3' side chains. Enzyme inhibition measured in vitro.","limitations":"Short abstract with limited potency and selectivity data. In-vivo antibacterial efficacy not demonstrated."},{"rthcId":"RPEP-00831","title":"Close apposition of dynorphin-positive nerve fibres to lymphocytes in the liver suggests opioidergic neuroimmunomodulation.","authors":"Kaiser, Matthias J T; Tiegs, Gisa; Neuhuber, Winfried L","year":2003,"journal":"Histochemistry and cell biology, 120(3), 213-21","doi":null,"pmid":"12904970","tags":["opioid-peptides","immune-function"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Dynorphin-positive nerve fibers were found in close apposition to lymphocytes in the rat liver, providing anatomical evidence for direct opioidergic neuroimmunomodulation of hepatic immune responses.","whyItMatters":"Direct nerve-immune communication in the liver through opioid peptides could explain how stress, pain, and opioid drugs affect liver immune function and disease.","specificNumbers":"","methodology":"Animal histological study using immunohistochemistry for dynorphin and lymphocyte markers in rat liver tissue. Nerve fiber-lymphocyte spatial relationships quantified.","limitations":"Anatomical study showing proximity, not functional communication. The functional consequences of dynorphin-lymphocyte interaction in the liver were not tested."},{"rthcId":"RPEP-00832","title":"The regulation of steroidogenesis by opioid peptides in porcine theca cells.","authors":"Kaminski, T; Siawrys, G; Bogacka, I; Okrasa, S; Przala, J","year":2003,"journal":"Animal reproduction science, 78(1-2), 71-84","doi":null,"pmid":"12753784","tags":["opioid-peptides","fertility","hormone-optimization"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Mu-opioid receptor agonists inhibited basal and LH-stimulated progesterone and androstenedione production in porcine theca cells in a dose-dependent manner, demonstrating direct opioid peptide control of ovarian steroidogenesis.","whyItMatters":"Opioid control of ovarian hormones explains why chronic opioid use causes menstrual irregularities and fertility problems, and why stress and pain affect reproductive function.","specificNumbers":"","methodology":"In-vitro study using cultured porcine theca cells from large follicles. Mu-opioid receptor agonists at various concentrations (1-1000 nM) with and without LH stimulation. Progesterone and androstenedione measured.","limitations":"In-vitro porcine theca cells. Human ovarian cells may respond differently. Only mu-receptor tested; delta and kappa effects unknown."},{"rthcId":"RPEP-00833","title":"Epithalon peptide induces telomerase activity and telomere elongation in human somatic cells.","authors":"Khavinson, V Kh; Bondarev, I E; Butyugov, A A","year":2003,"journal":"Bulletin of experimental biology and medicine, 135(6), 590-2","doi":null,"pmid":"12937682","tags":["anti-aging","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Epithalon peptide (Ala-Glu-Asp-Gly) induced telomerase catalytic subunit (hTERT) expression, telomerase enzymatic activity, and telomere elongation in telomerase-negative human fetal fibroblasts.","whyItMatters":"Telomere shortening is one of the most fundamental mechanisms of aging. A simple peptide that reactivates telomerase could potentially slow or reverse cellular aging.","specificNumbers":"","methodology":"In-vitro study adding Epithalon to telomerase-negative human fetal fibroblast cultures. Telomerase catalytic subunit expression, enzymatic activity, and telomere length measured.","limitations":"In-vitro fibroblast study. Telomerase activation could promote cancer if uncontrolled. In-vivo effects and safety not assessed. Very short abstract limits detail."},{"rthcId":"RPEP-00834","title":"Peptides of pineal gland and thymus prolong human life.","authors":"Khavinson, Vladimir Kh; Morozov, Vyacheslav G","year":2003,"journal":"Neuro endocrinology letters, 24(3-4), 233-40","doi":null,"pmid":"14523363","tags":["anti-aging","thymosin"],"studyType":"clinical-trial","evidenceStrength":"low","keyFinding":"In a 6-8 year follow-up study of 266 elderly people, treatment with thymic peptide (Thymalin) and pineal peptide (Epithalamin) bioregulators for 2-3 years was associated with dramatic reductions in mortality: 2.0-2.1 times lower with Thymalin, 1.6-1.8 times lower with Epithalamin, and 2.5 times lower with the combination. The most striking result: patients treated with both peptides annually for 6 years showed a 4.1-fold decrease in mortality compared to controls.\n\nTreated patients also showed improved cardiovascular, endocrine, immune, and nervous system function, a 2.0-2.4 fold reduction in respiratory infections, and lower rates of ischemic heart disease, hypertension, osteoarthritis, and osteoporosis.","whyItMatters":"This is one of the foundational studies from the Russian peptide bioregulator tradition — a body of work claiming that short peptides derived from thymus and pineal gland tissue can reverse aging and extend life. The reported effects are extraordinary (4.1x mortality reduction), which is precisely why the study is both influential in the bioregulator community and viewed with skepticism by mainstream Western medicine. The study is important to understand because it drives significant consumer interest in peptide bioregulators.","specificNumbers":"n=266 · 6-8 year follow-up · Thymalin treatment: 2.0-2.1x lower mortality · Epithalamin: 1.6-1.8x lower mortality · Combined: 2.5x lower mortality · 6-year annual treatment: 4.1x lower mortality · 2.0-2.4x fewer respiratory infections","methodology":"Clinical study of 266 elderly people at Russian and Ukrainian gerontology institutes. Patients received thymic peptide (Thymalin), pineal peptide (Epithalamin), or both for 2-3 years initially, with a subset receiving annual treatment for 6 years. Health outcomes including mortality, disease incidence, and system function were tracked for 6-8 years and compared to a control group.","limitations":"Major methodological concerns: the study does not describe randomization procedures, blinding, or control group selection in the abstract. The extraordinary magnitude of effects (4.1x mortality reduction) would be unprecedented in modern clinical medicine and warrants extreme skepticism without independent replication. Published in a low-impact journal. The research comes from scientists who developed and advocate for these specific products, creating significant conflict of interest. No independent Western replication exists."},{"rthcId":"RPEP-00835","title":"Delta sleep inducing peptide (DSIP): effect on respiration activity in rat brain mitochondria and stress protective potency under experimental hypoxia.","authors":"Khvatova, Elena M; Samartzev, Victor N; Zagoskin, Pavel P; Prudchenko, Igor A; Mikhaleva, Inessa I","year":2003,"journal":"Peptides, 24(2), 307-11","doi":null,"pmid":"12668217","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00836","title":"Plasma endothelin-1 levels and clinical correlates in patients with chronic heart failure.","authors":"Kinugawa, Toru; Kato, Masahiko; Ogino, Kazuhide; Osaki, Shuichi; Igawa, Osamu; Hisatome, Ichiro; Shigemasa, Chiaki","year":2003,"journal":"Journal of cardiac failure, 9(4), 318-24","doi":null,"pmid":"13680553","tags":["natriuretic-peptides","cardiovascular"],"studyType":"cross-sectional","evidenceStrength":"moderate","keyFinding":"Plasma ET-1 correlated with NYHA class, exercise capacity, and BNP in CHF patients, and independently predicted adverse outcomes, providing complementary prognostic information to natriuretic peptides.","whyItMatters":"ET-1 captures vascular dysfunction that BNP doesn't. Together, they provide a more complete picture of heart failure severity and prognosis than either alone.","specificNumbers":"","methodology":"Cross-sectional study measuring plasma ET-1, BNP, ANP, and clinical parameters (NYHA class, peak VO2, echocardiography) in chronic heart failure patients with outcome follow-up.","limitations":"Cross-sectional with outcome follow-up. Specific ET-1 cutoffs for clinical decisions not established. ET-1 assay variability is a concern."},{"rthcId":"RPEP-00837","title":"Selank and short peptides of the tuftsin family in the regulation of adaptive behavior in stress.","authors":"Kozlovskaya, M M; Kozlovskii, I I; Val'dman, E A; Seredenin, S B","year":2003,"journal":"Neuroscience and behavioral physiology, 33(9), 853-60","doi":null,"pmid":"14969422","tags":["selank","anxiety-mood","neuropeptides"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Selank and tuftsin-family peptides improved adaptive behavior in stressed animals in a phenotype-dependent manner, with different peptides optimal for different emotional reactivity types — supporting personalized peptide anxiolytic therapy.","whyItMatters":"One-size-fits-all anxiolytics often fail. Matching peptide type to personality/temperament type could improve treatment outcomes — precision psychiatry at the peptide level.","specificNumbers":"","methodology":"Animal behavioral study comparing Selank and tuftsin-family peptides in rats and mice pre-classified by emotional reactivity phenotype. Stress adaptation behaviors measured across different emotional types.","limitations":"Animal behavioral study. Human temperament is more complex. The molecular basis for phenotype-dependent responses was not determined."},{"rthcId":"RPEP-00838","title":"The optimizing action of the synthetic peptide Selank on a conditioned active avoidance reflex in rats.","authors":"Kozlovskii, I I; Danchev, N D","year":2003,"journal":"Neuroscience and behavioral physiology, 33(7), 639-43","doi":null,"pmid":"14552529","tags":["selank","cognitive-enhancement"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Selank selectively enhanced conditioned avoidance learning and memory in rats with initially low learning ability while minimally affecting normal learners, demonstrating deficit-correcting rather than general cognitive enhancement.","whyItMatters":"A cognitive enhancer that specifically helps those with deficits — without over-stimulating normal function — is the ideal nootropic profile. This selectivity suggests safety and appropriateness for clinical cognitive impairment.","specificNumbers":"","methodology":"Animal learning study using shuttle box conditioned avoidance. Rats classified as low or normal learners. Selank administered before training. Learning acquisition and 24-hour memory retention measured.","limitations":"Rat learning model. Conditioned avoidance is a specific learning type; effects on other cognitive domains unknown."},{"rthcId":"RPEP-00839","title":"Actions of neuropeptide Y and growth hormone secretagogues in the arcuate nucleus and ventromedial hypothalamic nucleus.","authors":"Kumarnsit, Ekkasit; Johnstone, Louise E; Leng, Gareth","year":2003,"journal":"The European journal of neuroscience, 17(5), 937-44","doi":null,"pmid":"12653970","tags":["ghrp","neuropeptides","hormone-optimization"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"GH secretagogues primarily activated arcuate nucleus neurons while NPY activated both arcuate and ventromedial hypothalamic neurons, demonstrating distinct appetite-stimulating circuits despite similar feeding outcomes.","whyItMatters":"Understanding which brain circuits each appetite signal uses enables more precise drug targeting — blocking specific circuits could reduce appetite stimulation while preserving other functions.","specificNumbers":"","methodology":"Animal study using Fos immunohistochemistry and electrophysiology to map GH secretagogue versus NPY neuronal activation patterns in the arcuate and ventromedial hypothalamic nuclei.","limitations":"Rat brain mapping. Fos and electrophysiology provide complementary but indirect measures of circuit engagement."},{"rthcId":"RPEP-00840","title":"Developmental changes in the inhibition of cultured rat uterine cell proliferation by opioid peptides.","authors":"Környei, J L; Vértes, Z; Kovács, K A; Göcze, P M; Vértes, M","year":2003,"journal":"Cell proliferation, 36(3), 151-63","doi":null,"pmid":"12814431","tags":["opioid-peptides","fertility"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Opioid peptides directly inhibited uterine cell proliferation in a developmental stage-dependent manner: strongest in immature tissue, diminishing with maturation, with different receptor subtypes active at different stages.","whyItMatters":"Opioid control of uterine development explains why opioid exposure during puberty could affect reproductive organ development, relevant for adolescent opioid use and maternal opioid exposure.","specificNumbers":"","methodology":"In-vitro study using cultured rat uterine cells from prepubertal, pubertal, and adult stages. Dynorphin, met-enkephalin, and beta-endorphin effects on proliferation measured. Receptor specificity determined with selective antagonists.","limitations":"In-vitro rat uterine cells. Human uterine development may differ. The in-vivo significance of opioid growth regulation needs confirmation."},{"rthcId":"RPEP-00841","title":"Utilization of a beta-aminophosphotyrosyl mimetic in the design and synthesis of macrocyclic Grb2 SH2 domain-binding peptides.","authors":"Lee, Kyeong; Zhang, Manchao; Liu, Hongpeng; Yang, Dajun; Burke, Terrence R","year":2003,"journal":"Journal of medicinal chemistry, 46(13), 2621-30","doi":null,"pmid":"12801226","tags":["cyclic-peptides","cancer","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"A macrocyclic peptide incorporating beta-aminophosphotyrosyl mimetic achieved potent Grb2 SH2 domain binding through conformational restriction, demonstrating macrocyclic drug design for cancer signaling disruption.","whyItMatters":"Protein-protein interactions drive cancer but are notoriously difficult drug targets. Macrocyclic peptides can achieve the large binding surfaces needed to disrupt these interactions — a key cancer drug design strategy.","specificNumbers":"","methodology":"In-vitro study. Macrocyclic peptide designed with phosphotyrosyl mimetic for Grb2 SH2 binding. Binding affinity measured by surface plasmon resonance. Comparison to linear counterparts.","limitations":"In-vitro binding only. Cell-based activity and in-vivo efficacy not demonstrated. Oral bioavailability of macrocyclic phosphopeptide mimetics is challenging."},{"rthcId":"RPEP-00842","title":"Impact of pramlintide on glucose fluctuations and postprandial glucose, glucagon, and triglyceride excursions among patients with type 1 diabetes intensively treated with insulin pumps.","authors":"Levetan, Claresa; Want, Laura L; Weyer, Christian; Strobel, Susan A; Crean, John; Wang, Yan; Maggs, David G; Kolterman, Orville G; Chandran, Manju; Mudaliar, Sunder R; Henry, Robert R","year":2003,"journal":"Diabetes care, 26(1), 1-8","doi":null,"pmid":"12502651","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00843","title":"Tumour necrosis factor alpha and nuclear factor kappaB inhibit transcription of human TFF3 encoding a gastrointestinal healing peptide.","authors":"Loncar, M B; Al-azzeh, E-d; Sommer, P S M; Marinovic, M; Schmehl, K; Kruschewski, M; Blin, N; Stohwasser, R; Gött, P; Kayademir, T","year":2003,"journal":"Gut, 52(9), 1297-303","doi":null,"pmid":"12912861","tags":["gut-healing","inflammation"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"TNF-alpha inhibited TFF3 transcription through NF-κB activation in intestinal cells, creating a pathogenic feedback loop where inflammation simultaneously damages the gut AND suppresses its natural repair peptide.","whyItMatters":"Understanding why the gut can't heal in IBD — because inflammation actively suppresses healing peptides — reveals the need for dual-action therapies that reduce inflammation AND promote repair simultaneously.","specificNumbers":"","methodology":"In-vitro study using intestinal cell lines. TNF-alpha effects on TFF3 gene transcription measured. NF-κB involvement confirmed by reporter assays and NF-κB inhibitors.","limitations":"In-vitro intestinal cell lines. The magnitude of TFF3 suppression in intact IBD tissue may differ. Other repair mechanisms beyond TFF3 exist."},{"rthcId":"RPEP-00844","title":"State-dependent modulation of feeding behavior by proopiomelanocortin-derived beta-endorphin.","authors":"Low, Malcolm J; Hayward, Michael D; Appleyard, Suzanne M; Rubinstein, Marcelo","year":2003,"journal":"Annals of the New York Academy of Sciences, 994, 192-201","doi":null,"pmid":"12851316","tags":["opioid-peptides","weight-loss"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"POMC-derived beta-endorphin selectively modulated the appetitive (wanting/seeking) phase of feeding behavior in a deprivation-state-dependent manner, separating opioid reward from hunger-driven consumption.","whyItMatters":"If opioids control food wanting (reward/pleasure) rather than hunger, opioid-targeted drugs could treat binge eating and food addiction without affecting normal hunger-driven eating.","specificNumbers":"","methodology":"Animal study using POMC-deficient mice (beta-endorphin lacking). Appetitive (food seeking) and consummatory (eating) behaviors measured separately under different deprivation states.","limitations":"POMC-deficient mice lack multiple peptides (alpha-MSH, ACTH) besides beta-endorphin. The specific contribution of beta-endorphin versus other POMC products is difficult to isolate."},{"rthcId":"RPEP-00845","title":"New insights into the functions of alpha-MSH and related peptides in the immune system.","authors":"Luger, Thomas A; Scholzen, Thomas E; Brzoska, Thomas; Böhm, Markus","year":2003,"journal":"Annals of the New York Academy of Sciences, 994, 133-40","doi":null,"pmid":"12851308","tags":["kpv","immune-function","inflammation"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Alpha-MSH and KPV serve triple immune functions: anti-inflammatory (NF-κB inhibition, cytokine suppression), antimicrobial (direct pathogen killing), and immunomodulatory (melanocortin receptor-mediated immune cell regulation) — a comprehensive immune regulatory system.","whyItMatters":"A natural peptide system that simultaneously fights infection AND controls inflammation is therapeutically ideal for conditions where both problems coexist — IBD, skin infections, wound healing.","specificNumbers":"","methodology":"Comprehensive review of alpha-MSH immunobiology covering receptor expression on immune cells, NF-κB inhibition mechanism, antimicrobial properties, and roles in innate and adaptive immunity.","limitations":"Review from 2003. Some proposed immune mechanisms were still being validated. Clinical translation of KPV was in early stages."},{"rthcId":"RPEP-00846","title":"Different mechanisms of intrinsic pain inhibition in early and late inflammation.","authors":"Machelska, Halina; Schopohl, Julia K; Mousa, Shaaban A; Labuz, Dominika; Schäfer, Michael; Stein, Christoph","year":2003,"journal":"Journal of neuroimmunology, 141(1-2), 30-9","doi":null,"pmid":"12965251","tags":["opioid-peptides","pain","immune-function","inflammation"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Early inflammatory pain inhibition was mediated by CRF-triggered opioid release from immune cells, while late inflammation used chemokine (CXCL1/2)-stimulated opioid release — the intrinsic pain control mechanism evolves with inflammation maturation.","whyItMatters":"Matching pain treatment to inflammation stage could improve outcomes. Early inflammation responds to CRF-pathway drugs; late inflammation to chemokine-pathway interventions.","specificNumbers":"","methodology":"Animal study in rats with Freund's adjuvant inflammation. CRF and chemokine receptor antagonists tested at early (6-hour) and late (4-day) inflammation timepoints to dissect opioid release mechanisms.","limitations":"Rat adjuvant inflammation model. The exact immune cell types releasing opioids at each stage were not fully characterized."},{"rthcId":"RPEP-00847","title":"Sensitization of outer-membrane mutants of Salmonella typhimurium and Pseudomonas aeruginosa to antimicrobial peptides under high pressure.","authors":"Masschalck, Barbara; Deckers, Daphne; Michiels, Chris W","year":2003,"journal":"Journal of food protection, 66(8), 1360-7","doi":null,"pmid":"12929820","tags":["antimicrobial-peptides","infection"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"High hydrostatic pressure sensitized Salmonella typhimurium and Pseudomonas aeruginosa outer-membrane mutants to lactoferrin, lactoferricin, and other antimicrobial peptides through outer membrane disruption.","whyItMatters":"Gram-negative bacteria are the hardest to treat with antimicrobial peptides. Combining pressure disruption with peptide exposure could make previously resistant bacteria treatable.","specificNumbers":"","methodology":"In-vitro study applying high hydrostatic pressure to gram-negative bacteria before or simultaneously with antimicrobial peptide exposure. MIC/MBC determinations for multiple peptides under pressure-treated conditions.","limitations":"In-vitro study. Clinical application of high-pressure treatment is limited to food processing and potentially wound care. The pressures used may not be achievable in clinical settings."},{"rthcId":"RPEP-00848","title":"Changes in appetite and body weight in response to long-term oral administration of the ghrelin agonist GHRP-2 in growth hormone deficient children.","authors":"Mericq, Verónica; Cassorla, Fernando; Bowers, Cyril Y; Avila, Alejandra; Gonen, Boas; Merriam, George R","year":2003,"journal":"Journal of pediatric endocrinology & metabolism : JPEM, 16(7), 981-5","doi":null,"pmid":"14513874","tags":["ghrp","weight-loss","hormone-optimization","clinical-trials"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"Chronic oral GHRP-2 in GH-deficient adults produced persistent increases in appetite and body weight alongside GH/IGF-1 elevation, confirming sustained orexigenic effects of long-term GH secretagogue therapy.","whyItMatters":"The persistent appetite increase from GH secretagogues is both a feature (for cachexia treatment) and a bug (for patients wanting GH benefits without weight gain). This defines the clinical trade-off.","specificNumbers":"","methodology":"Clinical trial of oral GHRP-2 in GH-deficient adults. Appetite (subjective assessment), body weight, GH, and IGF-1 measured over the treatment course.","limitations":"Open-label clinical trial. Specific appetite and weight quantification limited in abstract. The body weight gain composition (fat vs lean) not detailed."},{"rthcId":"RPEP-00849","title":"PT-141: a melanocortin agonist for the treatment of sexual dysfunction.","authors":"Molinoff, P B; Shadiack, A M; Earle, D; Diamond, L E; Quon, C Y","year":2003,"journal":"Annals of the New York Academy of Sciences, 994, 96-102","doi":null,"pmid":"12851303","tags":["pt-141","sexual-health","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"PT-141 (bremelanotide) induced sexual arousal in both male and female animals through central MC3R/MC4R activation, representing a mechanistically novel approach to sexual dysfunction treatment through brain desire pathways rather than peripheral blood flow.","whyItMatters":"Sexual dysfunction affects 40%+ of adults. Current drugs (Viagra) only address blood flow. PT-141 addresses desire/arousal centrally — helping patients where existing drugs fail.","specificNumbers":"","methodology":"Preclinical studies in male and female animal models. PT-141 administered centrally and peripherally. Erectile and arousal responses measured. Receptor specificity confirmed with selective antagonists.","limitations":"Animal studies; human sexual dysfunction is more complex. Central peptide delivery may limit route options (intranasal or SC)."},{"rthcId":"RPEP-00850","title":"Prevention of polyglutamine oligomerization and neurodegeneration by the peptide inhibitor QBP1 in Drosophila.","authors":"Nagai, Yoshitaka; Fujikake, Nobuhiro; Ohno, Katsuhito; Higashiyama, Hiroyuki; Popiel, Helena A; Rahadian, Julia; Yamaguchi, Masamitsu; Strittmatter, Warren J; Burke, James R; Toda, Tatsushi","year":2003,"journal":"Human molecular genetics, 12(11), 1253-9","doi":null,"pmid":"12761040","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00851","title":"Ghrelin, a novel growth hormone-releasing peptide, in the treatment of chronic heart failure.","authors":"Nagaya, Noritoshi; Kangawa, Kenji","year":2003,"journal":"Regulatory peptides, 114(2-3), 71-7","doi":null,"pmid":"12832093","tags":["ghrp","cardiovascular","hormone-optimization"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Ghrelin provides triple-mechanism benefit for heart failure: GH-mediated cardiac improvement, appetite stimulation counteracting cachexia, and direct GHS-R-mediated cardioprotection — addressing three core disease components.","whyItMatters":"Heart failure treatments typically target only one mechanism. Ghrelin simultaneously addresses cardiac dysfunction, wasting, and cellular damage — a comprehensive single-agent approach.","specificNumbers":"","methodology":"Review of ghrelin's cardiac, metabolic, and direct cardioprotective effects with application to heart failure therapy.","limitations":"Review of largely preclinical data. Human heart failure trials with ghrelin were limited at time of publication."},{"rthcId":"RPEP-00852","title":"Ghrelin improves left ventricular dysfunction and cardiac cachexia in heart failure.","authors":"Nagaya, Noritoshi; Kangawa, Kenji","year":2003,"journal":"Current opinion in pharmacology, 3(2), 146-51","doi":null,"pmid":"12681236","tags":["ghrp","cardiovascular","weight-loss"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Ghrelin treatment improved LVEF, increased lean body mass, enhanced exercise capacity, and reduced neurohormonal activation in heart failure, simultaneously addressing cardiac dysfunction and cachexia.","whyItMatters":"Cardiac cachexia is a death sentence — patients who develop it have dramatically worse survival. Ghrelin is the first agent to simultaneously improve heart function AND reverse the wasting.","specificNumbers":"","methodology":"Review of ghrelin effects on cardiac function, body composition, exercise capacity, and neurohormonal status in heart failure models and early clinical studies.","limitations":"Review of mostly small studies. Large randomized trials needed. Whether ghrelin benefits are sustained long-term is unknown."},{"rthcId":"RPEP-00853","title":"Thymosin beta 4 and a synthetic peptide containing its actin-binding domain promote dermal wound repair in db/db diabetic mice and in aged mice.","authors":"Philp, Deborah; Badamchian, Mahnaz; Scheremeta, Brooke; Nguyen, Mychi; Goldstein, Allan L; Kleinman, Hynda K","year":2003,"journal":"Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society, 11(1), 19-24","doi":null,"pmid":"12581423","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00854","title":"Growth hormone secretagogues modulate the electrical and contractile properties of rat skeletal muscle through a ghrelin-specific receptor.","authors":"Pierno, Sabata; De Luca, Annamaria; Desaphy, Jean-François; Fraysse, Bodvael; Liantonio, Antonella; Didonna, Maria Paola; Lograno, Marcello; Cocchi, Daniela; Smith, Roy G; Camerino, Diana Conte","year":2003,"journal":"British journal of pharmacology, 139(3), 575-84","doi":null,"pmid":"12788817","tags":["ghrp","muscle-recovery","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"GH secretagogues directly modulated skeletal muscle electrical excitability and contractile properties through a muscle-specific ghrelin-type receptor, independent of GH release — revealing direct muscle-targeting activity.","whyItMatters":"Direct muscle effects mean GH secretagogues could improve muscle function even in conditions where GH itself doesn't work well (like GH resistance in critical illness).","specificNumbers":"","methodology":"In-vitro study using isolated rat skeletal muscle. GH secretagogue effects on membrane potential, action potential parameters, and contractile force measured by intracellular recording and force transduction.","limitations":"In-vitro isolated muscle. Whether these direct effects are clinically significant in vivo alongside GH-mediated effects needs determination."},{"rthcId":"RPEP-00855","title":"Long-term effects of short and long periods of maternal separation on brain opioid peptide levels in male Wistar rats.","authors":"Ploj, Karolina; Roman, Erika; Nylander, Ingrid","year":2003,"journal":"Neuropeptides, 37(3), 149-56","doi":null,"pmid":"12860112","tags":["opioid-peptides","anxiety-mood"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Both short and long maternal separation produced distinct, persistent alterations in brain opioid peptide levels (dynorphin, met-enkephalin) across reward and stress regions in adult rats, demonstrating lasting neurochemical consequences of early life experience.","whyItMatters":"Early life experience permanently shapes the opioid system that controls pain, pleasure, stress coping, and addiction. Understanding these lasting changes explains why childhood adversity increases adult psychiatric risk.","specificNumbers":"","methodology":"Animal study. Rat pups separated 15 min or 360 min daily for postnatal days 1-14. Adult brain opioid peptide levels measured by RIA in 8+ brain regions including reward, stress, and limbic areas.","limitations":"Rat model of early separation. Human childhood experience is more varied and complex. Brain peptide measurements at one adult timepoint may not capture dynamic regulation."},{"rthcId":"RPEP-00856","title":"Expression of the cathelicidin LL-37 is modulated by short chain fatty acids in colonocytes: relevance of signalling pathways.","authors":"Schauber, J; Svanholm, C; Termén, S; Iffland, K; Menzel, T; Scheppach, W; Melcher, R; Agerberth, B; Lührs, H; Gudmundsson, G H","year":2003,"journal":"Gut, 52(5), 735-41","doi":null,"pmid":"12692061","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In healthy human colon and ileum tissue, LL-37 expression was restricted to differentiated epithelial cells. In cell culture, butyrate, isobutyrate, propionate, and the histone deacetylase inhibitor trichostatin A all increased LL-37 expression in colon cells alongside cell differentiation. Flavone also induced LL-37 but without affecting differentiation, demonstrating that LL-37 can be upregulated independently.\n\nCritically, when the MEK-ERK signaling pathway was blocked, butyrate-induced LL-37 expression was abolished — even though cell differentiation was actually enhanced. Conversely, blocking the p38/MAP kinase pathway stopped cell differentiation without inhibiting LL-37 expression. This separation of signaling pathways means LL-37 production and cell maturation are independently controllable, opening the possibility of specifically boosting antimicrobial peptide production through targeted dietary or pharmacological interventions.","whyItMatters":"This landmark study established that your gut bacteria, through the SCFAs they produce from dietary fiber, can directly regulate the production of antimicrobial peptides in the colon. This is a fundamental connection between diet, the microbiome, and innate immune defense. It provides a scientific basis for why high-fiber diets may protect against gut infections and inflammatory bowel disease — your gut bacteria are literally feeding the cells that make natural antibiotics.","specificNumbers":"","methodology":"Researchers examined LL-37 expression in vivo using immunohistochemistry on human colon and ileum tissue biopsies from healthy adults. In vitro, they treated colon epithelial cell lines with various short chain fatty acids, cytokines, and flavone, measuring LL-37 expression by real-time qRT-PCR and cell differentiation by alkaline phosphatase activity. They used specific inhibitors of the MEK-ERK and p38/MAP kinase pathways to dissect which signaling routes controlled LL-37 expression versus cell differentiation.","limitations":"The in vitro experiments used colon cancer cell lines, which may not perfectly represent normal colon epithelium. The in vivo immunohistochemistry provided localization data but not quantitative expression levels. The study did not measure LL-37 protein levels (only mRNA and immunostaining), and did not test whether increased LL-37 expression translates to functional antimicrobial activity. The specific SCFA concentrations used in culture may not exactly match physiological levels in the colon."},{"rthcId":"RPEP-00857","title":"The pharmacology of CP-154,526, a non-peptide antagonist of the CRH1 receptor: a review.","authors":"Seymour, Patricia A; Schmidt, Anne W; Schulz, David W","year":2003,"journal":"CNS drug reviews, 9(1), 57-96","doi":null,"pmid":"12595912","tags":["neuropeptides","anxiety-mood","peptide-design"],"studyType":"review","evidenceStrength":"strong","keyFinding":"CP-154,526 showed anxiolytic effects across multiple animal models, antidepressant activity, and HPA axis modulation without sedation, providing the most comprehensive validation of CRF1 antagonism as a psychiatric drug mechanism.","whyItMatters":"CP-154,526 proved the concept that blocking the stress hormone receptor can treat anxiety and depression — the scientific foundation for developing CRF1 antagonist drugs for psychiatry.","specificNumbers":"","methodology":"Comprehensive pharmacological review covering CP-154,526's receptor selectivity, anxiolytic activity across 5+ anxiety models, antidepressant effects, HPA axis modulation, and lack of sedation.","limitations":"Animal pharmacology. CP-154,526 itself wasn't developed clinically (other CRF1 antagonists were). Human clinical translation of CRF1 antagonism has had mixed results."},{"rthcId":"RPEP-00858","title":"Corticosteroid-impairment of healing and gastric pentadecapeptide BPC-157 creams in burned mice.","authors":"Sikiric, P; Seiwerth, S; Mise, S; Staresinic, M; Bedekovic, V; Zarkovic, N; Borovic, S; Gjurasin, M; Boban-Blagaic, A; Batelja, L; Rucman, R; Anic, T","year":2003,"journal":"Burns : journal of the International Society for Burn Injuries, 29(4), 323-34","doi":null,"pmid":"12781609","tags":["bpc-157","wound-healing","skin-repair","inflammation"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Topical BPC-157 cream reversed methylprednisolone-induced burn wound healing impairment in mice, restoring wound closure rates during concurrent steroid treatment.","whyItMatters":"Millions of patients need corticosteroids but suffer from impaired healing. A cream that reverses steroid-induced healing failure without interfering with steroid therapy fills a critical clinical gap.","specificNumbers":"","methodology":"Animal study in burned mice receiving methylprednisolone. BPC-157 cream applied topically to burn wounds. Wound healing rate (contraction, re-epithelialization) measured at multiple timepoints versus steroid-treated controls.","limitations":"Mouse burn model with specific steroid protocol. Human steroid-impaired wounds may respond differently. Optimal BPC-157 cream concentration not established."},{"rthcId":"RPEP-00859","title":"Peptidases prevent mu-opioid receptor internalization in dorsal horn neurons by endogenously released opioids.","authors":"Song, Bingbing; Marvizón, Juan Carlos G","year":2003,"journal":"The Journal of neuroscience : the official journal of the Society for Neuroscience, 23(5), 1847-58","doi":null,"pmid":"12629189","tags":["opioid-peptides","pain"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Multiple peptidase inhibition in rat spinal cord slices allowed endogenous opioid peptides to accumulate and trigger mu-opioid receptor internalization, revealing that rapid enzymatic degradation normally prevents full endogenous opioid receptor activation.","whyItMatters":"Boosting endogenous opioids by blocking their degradation could provide pain relief without the addiction risk of external opioid drugs — using the body's own painkillers more effectively.","specificNumbers":"","methodology":"In-vitro rat spinal cord slice study. Peptidase inhibitor cocktail applied. Mu-opioid receptor internalization measured as a marker of receptor activation by endogenous opioids released by electrical stimulation.","limitations":"In-vitro spinal cord slices. The degree of pain relief achievable in vivo through peptidase inhibition needs determination."},{"rthcId":"RPEP-00860","title":"Gastric pentadecapeptide BPC 157 accelerates healing of transected rat Achilles tendon and in vitro stimulates tendocytes growth.","authors":"Staresinic, M; Sebecic, B; Patrlj, L; Jadrijevic, S; Suknaic, S; Perovic, D; Aralica, G; Zarkovic, N; Borovic, S; Srdjak, M; Hajdarevic, K; Kopljar, M; Batelja, L; Boban-Blagaic, A; Turcic, I; Anic, T; Seiwerth, S; Sikiric, P","year":2003,"journal":"Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 21(6), 976-83","doi":null,"pmid":"14554208","tags":["bpc-157","muscle-recovery","wound-healing"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"BPC-157 accelerated transected Achilles tendon healing in rats (improved biomechanics and histology) and directly stimulated tendocyte proliferation in vitro, demonstrating both functional repair and cellular mechanism.","whyItMatters":"Tendon injuries are among the most common orthopedic problems, affecting athletes and the general population. Faster, better tendon healing would reduce disability and recovery time for millions.","specificNumbers":"","methodology":"Animal study: transected rat Achilles tendon treated with BPC-157. Biomechanical testing and histological assessment. In-vitro: tendocyte proliferation measured after BPC-157 exposure.","limitations":"Rat tendon transection model. Complete transection is more severe than typical human tendon injuries. Optimal dose, route, and timing for tendon repair not established."},{"rthcId":"RPEP-00861","title":"Stress responsive neurohormones in depression and anxiety.","authors":"Ströhle, A; Holsboer, F","year":2003,"journal":"Pharmacopsychiatry, 36 Suppl 3, S207-14","doi":null,"pmid":"14677081","tags":["neuropeptides","natriuretic-peptides","anxiety-mood"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Depression, panic, and PTSD show distinct stress neurohormone patterns (CRF, vasopressin, NPY alterations), with ANP demonstrating anxiolytic properties — disorder-specific peptide profiles enabling targeted therapy.","whyItMatters":"Different stress disorders involve different peptide systems. Matching treatment to the specific neurohormonal pattern could dramatically improve psychiatric outcomes.","specificNumbers":"","methodology":"Review of clinical studies measuring stress neurohormones in depression, panic disorder, and PTSD patients, with emerging data on ANP's anxiolytic effects.","limitations":"Review of clinical data with varying study quality. The clinical utility of neurohormonal profiling for treatment selection was not established."},{"rthcId":"RPEP-00862","title":"The effect of treatment with the oral growth hormone (GH) secretagogue MK-677 on GH isoforms.","authors":"Svensson, J; Boguszewski, C L; Shibata, F; Carlsson, B; Carlsson, L M S; Bengtsson, B-A","year":2003,"journal":"Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society, 13(1), 1-7","doi":null,"pmid":"12550076","tags":["mk-677","hormone-optimization"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"MK-677 treatment increased the proportion of non-22kDa and 20kDa GH isoforms relative to total GH in obese subjects, demonstrating that GH secretagogues alter the GH isoform profile differently from exogenous GH replacement.","whyItMatters":"Different GH isoforms may have different biological effects (growth, fat metabolism, etc.). If MK-677 produces a unique GH isoform mix, its clinical effects may differ from standard GH injections in subtle but important ways.","specificNumbers":"","methodology":"Clinical trial substudy from the MK-677 body composition study. GH isoform analysis using size-exclusion HPLC and immunoassays in obese males during 8-week MK-677 treatment.","limitations":"Isoform analysis in one study population. The clinical significance of altered isoform ratios is unknown."},{"rthcId":"RPEP-00863","title":"Endogenous opioid peptides contribute to antinociceptive potency of intrathecal [Dmt1]DALDA.","authors":"Szeto, Hazel H; Soong, Yi; Wu, Dunli; Qian, XuanXuan; Zhao, Guo-Min","year":2003,"journal":"The Journal of pharmacology and experimental therapeutics, 305(2), 696-702","doi":null,"pmid":"12606628","tags":["opioid-peptides","pain"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Intrathecal [Dmt1]DALDA analgesia was partly mediated by endogenous opioid peptide release (confirmed by opioid antiserum blocking), demonstrating drug-induced amplification through the endogenous opioid system.","whyItMatters":"If opioid drugs work partly by triggering endogenous opioid release, this amplification could be enhanced for better pain relief at lower drug doses — reducing addiction risk.","specificNumbers":"","methodology":"Animal study. Intrathecal [Dmt1]DALDA in mice. Antinociception measured with and without ICV/intrathecal opioid antisera to determine contribution of endogenous opioid release to the drug's analgesic effect.","limitations":"Mouse study. The specific endogenous opioids released were not identified. The relative contribution of direct versus endogenous activation varies by drug dose."},{"rthcId":"RPEP-00864","title":"Aggression and the three opioid families (endorphins, enkephalins, and dynorphins) in mice.","authors":"Tordjman, Sylvie; Carlier, Michèle; Cohen, David; Cesselin, François; Bourgoin, Sylvie; Colas-Linhart, Nicole; Petiet, Anne; Perez-Diaz, Fernando; Hamon, Michel; Roubertoux, Pierre L","year":2003,"journal":"Behavior genetics, 33(5), 529-36","doi":null,"pmid":"14574130","tags":["opioid-peptides","anxiety-mood"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"All three endogenous opioid peptide families (endorphins, enkephalins, dynorphins) inversely correlated with aggression across brain regions, with each acting through distinct receptor systems (mu, delta, kappa) and neural circuits.","whyItMatters":"Aggression underlies domestic violence, criminal behavior, and psychiatric emergencies. Understanding that ALL three opioid systems suppress aggression identifies multiple therapeutic targets.","specificNumbers":"","methodology":"Animal study measuring opioid peptide levels in aggression-related brain regions and correlating with intermale aggression behavior. Selective opioid receptor antagonists tested for aggression effects.","limitations":"Mouse intermale aggression model. Human aggression is more complex. Correlation between peptide levels and behavior doesn't prove causation."},{"rthcId":"RPEP-00865","title":"Milk bioactive peptides and beta-casomorphins induce mucus release in rat jejunum.","authors":"Trompette, Aurélien; Claustre, Jean; Caillon, Fabienne; Jourdan, Gérard; Chayvialle, Jean Alain; Plaisancié, Pascale","year":2003,"journal":"The Journal of nutrition, 133(11), 3499-503","doi":null,"pmid":"14608064","tags":["bioactive-food-peptides","opioid-peptides","gut-healing"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Beta-casomorphin-7 and casein hydrolysate stimulated mucus release in rat jejunum through mu-opioid receptor activation, providing a direct mechanism for dairy-derived gut protection through opioid peptide signaling.","whyItMatters":"Mucus protects the gut from infection and inflammation. If dairy-derived peptides boost mucus production, milk consumption directly strengthens the gut barrier — a functional food mechanism with clinical implications for IBD and gut health.","specificNumbers":"","methodology":"In-vitro rat jejunum mucus secretion study. Casein enzymatic hydrolysate and purified beta-casomorphin-7 tested. Mucus release quantified. Naloxone (opioid antagonist) used to confirm opioid receptor mediation.","limitations":"In-vitro rat intestine. Whether physiological concentrations of casomorphins from normal milk consumption achieve significant mucus stimulation is uncertain."},{"rthcId":"RPEP-00866","title":"Direct actions of urotensin II on the heart: implications for cardiac fibrosis and hypertrophy.","authors":"Tzanidis, Alex; Hannan, Ross D; Thomas, Walter G; Onan, Döne; Autelitano, Dominic J; See, Fiona; Kelly, Darren J; Gilbert, Richard E; Krum, Henry","year":2003,"journal":"Circulation research, 93(3), 246-53","doi":null,"pmid":"12842917","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00867","title":"Dynorphin B is an agonist of nuclear opioid receptors coupling nuclear protein kinase C activation to the transcription of cardiogenic genes in GTR1 embryonic stem cells.","authors":"Ventura, Carlo; Zinellu, Elisabetta; Maninchedda, Emiliana; Maioli, Margherita","year":2003,"journal":"Circulation research, 92(6), 623-9","doi":null,"pmid":"12623878","tags":["opioid-peptides","cardiovascular","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Dynorphin B activated nuclear opioid receptors coupling to nuclear PKC activation, which induced cardiac transcription factors (GATA-4, Nkx-2.5) for cardiogenesis in embryonic stem cells — a novel nuclear signaling mechanism.","whyItMatters":"Nuclear opioid receptors are a new signaling paradigm. If opioid peptides directly control gene expression through nuclear receptors, their effects are more fundamental and long-lasting than surface receptor signaling alone.","specificNumbers":"","methodology":"In-vitro study using embryonic stem cells. Nuclear opioid receptor activation by dynorphin B, nuclear PKC signaling, and cardiac gene expression measured with subcellular fractionation.","limitations":"In-vitro stem cell model. Nuclear opioid receptor signaling in mature cardiac tissue needs confirmation."},{"rthcId":"RPEP-00868","title":"Protein kinase C signaling transduces endorphin-primed cardiogenesis in GTR1 embryonic stem cells.","authors":"Ventura, Carlo; Zinellu, Elisabetta; Maninchedda, Emiliana; Fadda, Marina; Maioli, Margherita","year":2003,"journal":"Circulation research, 92(6), 617-22","doi":null,"pmid":"12623877","tags":["opioid-peptides","cardiovascular","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Opioid-primed cardiogenesis in GTR1 embryonic stem cells was mediated by PKC epsilon nuclear translocation, which activated GATA-4 and Nkx-2.5 cardiac transcription — mapping the complete opioid-to-cardiac differentiation signaling cascade.","whyItMatters":"Knowing the exact signaling pathway (endorphin → PKC epsilon → cardiac genes) enables pharmaceutical intervention at each step — potentially directing stem cell cardiac differentiation more precisely.","specificNumbers":"","methodology":"In-vitro study using GTR1 embryonic stem cells. PKC epsilon translocation tracked during opioid-stimulated cardiogenesis. Selective PKC isoform inhibitors tested. GATA-4 and Nkx-2.5 expression measured.","limitations":"GTR1 stem cell model. The pathway in primary stem cells or in-vivo cardiac progenitors may differ."},{"rthcId":"RPEP-00869","title":"Lactoferricin derived from milk protein lactoferrin.","authors":"Wakabayashi, H; Takase, M; Tomita, M","year":2003,"journal":"Current pharmaceutical design, 9(16), 1277-87","doi":null,"pmid":"12769736","tags":["antimicrobial-peptides","infection","cancer"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Lactoferricin demonstrates antibacterial, antifungal, antiviral, antiparasitic, antitumor, and immunomodulatory activities — establishing it as a remarkably multi-functional peptide derived from the common milk protein lactoferrin.","whyItMatters":"A single milk-derived peptide with activity against bacteria, fungi, viruses, parasites, AND cancer represents an extraordinary natural therapeutic resource.","specificNumbers":"","methodology":"Review of lactoferricin biological activities covering antimicrobial spectrum, anticancer mechanisms, immunomodulatory effects, and structure-activity studies of synthetic analogs.","limitations":"Review from 2003. Some activities were at early characterization stages. In-vivo therapeutic efficacy for most applications was not established."},{"rthcId":"RPEP-00870","title":"Orexin-A-sensitive site for energy expenditure localized in the arcuate nucleus of the hypothalamus.","authors":"Wang, Jian; Osaka, Toshimasa; Inoue, Shuji","year":2003,"journal":"Brain research, 971(1), 128-34","doi":null,"pmid":"12691845","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00871","title":"Peripheral opioidergic regulation of the tracheobronchial mucociliary transport system.","authors":"Wang, Lian; Tiniakov, Ruslan L; Yeates, Donovan B","year":2003,"journal":"Journal of applied physiology (Bethesda, Md. : 1985), 94(6), 2375-83","doi":null,"pmid":"12611768","tags":["opioid-peptides","respiratory"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Peripheral opioid receptor activation in airway mucosa increased net water absorption, affecting mucociliary transport — identifying an opioidergic regulation of tracheobronchial respiratory defense mechanisms.","whyItMatters":"Airway mucus disorders (cystic fibrosis, COPD, asthma) need better treatments. The opioid system's role in regulating airway hydration opens new therapeutic avenues for mucus-related respiratory diseases.","specificNumbers":"","methodology":"Animal study measuring bidirectional water flux across airway mucosa with and without opioid agonists and antagonists. Mucociliary clearance rates assessed.","limitations":"Animal airway study. The clinical significance for human respiratory function and disease needs confirmation."},{"rthcId":"RPEP-00872","title":"Significance of serum atrial and brain natriuretic peptide release after coronary artery bypass grafting.","authors":"Watanabe, Masazumi; Egi, Koso; Hasegawa, Satoru; Tanaka, Hiroyuki; Ohshima, Hisanaga; Sakamoto, Tohru; Sunamori, Makoto","year":2003,"journal":"Surgery today, 33(9), 671-3","doi":null,"pmid":"12928843","tags":["natriuretic-peptides","cardiovascular"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Serial postoperative BNP levels predicted clinical complications and recovery trajectory after CABG, with persistent elevation identifying high-risk patients, while ANP was less discriminating.","whyItMatters":"Cardiac surgery carries significant complication risk. A simple blood test that identifies which patients will develop problems enables earlier intervention and better resource allocation.","specificNumbers":"","methodology":"Prospective cohort study measuring serial BNP and ANP before and at multiple timepoints after CABG. Clinical outcomes and complications tracked during recovery.","limitations":"Single-center cohort. Specific BNP cutoffs and timing for clinical decisions not established."},{"rthcId":"RPEP-00873","title":"Ghrelin promotes slow-wave sleep in humans.","authors":"Weikel, J C; Wichniak, A; Ising, M; Brunner, H; Friess, E; Held, K; Mathias, S; Schmid, D A; Uhr, M; Steiger, A","year":2003,"journal":"American journal of physiology. Endocrinology and metabolism, 284(2), E407-15","doi":null,"pmid":"12388174","tags":["neuropeptides","sleep"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"Intravenous ghrelin administration increased slow-wave sleep (deep sleep) across the total night and enhanced delta-wave activity during the second half of the night. REM sleep was reduced during the second third of the night, while other sleep stages were unaffected.\n\nGhrelin also stimulated multiple hormonal responses: growth hormone and prolactin levels were elevated throughout the night, and cortisol rose during the first half. Interestingly, the GH response was strongest after the first injection and weakest after the fourth, while cortisol showed the opposite pattern. Leptin levels were unaffected.","whyItMatters":"This is one of the earliest studies showing that ghrelin directly promotes deep sleep in humans. Deep slow-wave sleep is the most restorative sleep phase and declines with age. If ghrelin naturally promotes deep sleep, it explains why hunger and sleep are biologically linked, and why growth hormone secretagogues (which activate the ghrelin receptor) are commonly reported to improve sleep quality.","specificNumbers":"n=7 · 4 × 50 μg ghrelin IV boluses (hourly, 2200-0100) · Increased slow-wave sleep total night · Enhanced delta activity 2nd half · Reduced REM 2nd third · GH + prolactin elevated all night · Cortisol elevated 2200-0300","methodology":"Seven healthy men received either ghrelin (4 bolus IV injections of 50 μg each, given hourly between 10 PM and 1 AM) or placebo. Researchers recorded sleep EEG throughout the night and measured blood levels of growth hormone, ACTH, cortisol, prolactin, and leptin at regular intervals.","limitations":"Very small sample (n=7), all male. Single night of study per condition. Supraphysiological IV bolus dosing may not reflect natural ghrelin dynamics. No female participants. Short-term study doesn't address chronic effects."},{"rthcId":"RPEP-00874","title":"Dynorphinergic mechanism mediating endomorphin-2-induced antianalgesia in the mouse spinal cord.","authors":"Wu, Hsiang-En; Sun, Han-Sen; Darpolar, Moses; Leitermann, Randy J; Kampine, John P; Tseng, Leon F","year":2003,"journal":"The Journal of pharmacology and experimental therapeutics, 307(3), 1135-41","doi":null,"pmid":"14557378","tags":["opioid-peptides","pain"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"High-dose intrathecal endomorphin-2 produced anti-analgesia through spinal dynorphin release activating NMDA receptors, demonstrating a dose-dependent flip from opioid analgesia to opioid-induced pain generation.","whyItMatters":"Opioid-induced hyperalgesia (more pain from more opioids) is a major clinical problem. This study reveals the mechanism: excess opioid triggers dynorphin → NMDA activation → pain. Understanding this guides clinical opioid dosing.","specificNumbers":"","methodology":"Animal study. Intrathecal endomorphin-2 at escalating doses. At high doses (1.75-35 nmol), anti-analgesia measured. Anti-dynorphin antibodies and MK-801 (NMDA blocker) used to dissect the mechanism.","limitations":"Mouse study with intrathecal injection. The dose range where the flip occurs may differ in humans."},{"rthcId":"RPEP-00875","title":"Opioids and the apoptotic pathway in human cancer cells.","authors":"Zagon, Ian S; McLaughlin, Patricia J","year":2003,"journal":"Neuropeptides, 37(2), 79-88","doi":null,"pmid":"12747939","tags":["opioid-peptides","cancer"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Met-enkephalin (OGF) inhibited cancer proliferation through OGFr nuclear translocation and activation of p16/p21 cell cycle inhibitors across pancreatic, colon, and squamous cell cancers — a non-classical opioid anti-cancer mechanism.","whyItMatters":"A natural opioid peptide that suppresses cancer through tumor suppressor activation represents an entirely new anti-cancer mechanism. It could be boosted to enhance natural tumor control.","specificNumbers":"","methodology":"In-vitro study using three human cancer cell lines. OGF binding, OGFr localization, p16/p21 induction, and cell cycle arrest measured. Classical opioid receptor involvement excluded with selective antagonists.","limitations":"In-vitro cancer cell lines. The OGFr pathway's in-vivo significance and therapeutic potential need validation."},{"rthcId":"RPEP-00876","title":"Adrenomedullin and cancer.","authors":"Zudaire, E; Martínez, A; Cuttitta, F","year":2003,"journal":"Regulatory peptides, 112(1-3), 175-83","doi":null,"pmid":"12667640","tags":["neuropeptides","cancer","cardiovascular"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Adrenomedullin is overexpressed in many cancers where it promotes tumor growth, drives angiogenesis (tumor blood vessel formation), and may suppress anti-tumor immunity — positioning it as a multi-mechanism cancer therapy target.","whyItMatters":"Tumors need blood supply and immune evasion to grow. AM provides both. Blocking it could attack cancer from two directions simultaneously — an efficient therapeutic strategy.","specificNumbers":"","methodology":"Review of adrenomedullin expression in human cancers, its effects on tumor cell proliferation, angiogenesis, and immune modulation, with therapeutic targeting implications.","limitations":"Review of early-stage cancer AM biology. The therapeutic potential of AM blockade in cancer was largely conceptual at the time."},{"rthcId":"RPEP-00877","title":"Diamond 2004 Doubleblind Placebocontrolled Evaluation Off","authors":"","year":2004,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00878","title":"Iranmanesh 2004 Activation Of Somatostatinreceptor Subt","authors":"","year":2004,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00879","title":"Antiviral activity of antimicrobial cationic peptides against Junin virus and herpes simplex virus.","authors":"Albiol Matanic, Vanesa C; Castilla, Viviana","year":2004,"journal":"International journal of antimicrobial agents, 23(4), 382-9","doi":null,"pmid":"15081088","tags":["antimicrobial-peptides","infection"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Cecropin A, melittin, magainin, and indolicidin demonstrated antiviral activity against both Junin virus (arenavirus) and HSV-1, expanding the antimicrobial peptide antiviral spectrum to include hemorrhagic fever viruses.","whyItMatters":"Hemorrhagic fever viruses have very few treatment options. Antimicrobial peptides that can kill these dangerous viruses could serve as emergency treatments or prophylactics.","specificNumbers":"","methodology":"In-vitro antiviral study testing multiple cationic antimicrobial peptides against Junin virus and HSV-1 in cell culture. Cytopathic effect inhibition and viral titer reduction measured.","limitations":"In-vitro activity. Concentrations required may exceed achievable in-vivo levels. Toxicity of melittin and some peptides limits systemic use."},{"rthcId":"RPEP-00880","title":"Thymosin-alpha 1 plus interferon-alpha for naive patients with chronic hepatitis C: results of a randomized controlled pilot trial.","authors":"Andreone, P; Gramenzi, A; Cursaro, C; Felline, F; Loggi, E; D'Errico, A; Spinosa, M; Lorenzini, S; Biselli, M; Bernardi, M","year":2004,"journal":"Journal of viral hepatitis, 11(1), 69-73","doi":null,"pmid":"14738560","tags":["thymosin-alpha-1","infection","immune-function","clinical-trials"],"studyType":"RCT","evidenceStrength":"moderate","keyFinding":"Thymosin alpha-1 + interferon-alpha achieved 40% SVR versus 20% for interferon alone in naive chronic hepatitis C patients (n=22), demonstrating significant immune-mediated enhancement of antiviral efficacy.","whyItMatters":"Before direct-acting antivirals, hepatitis C treatment relied on interferon with limited success. Thymosin alpha-1 doubled the cure rate — a clinically meaningful improvement through immune enhancement.","specificNumbers":"","methodology":"Randomized controlled pilot study. 22 naive chronic HCV patients randomized to IFN-alpha + thymosin alpha-1 (n=11) or IFN-alpha alone (n=11). SVR (sustained virological response) as primary endpoint.","limitations":"Small pilot study (n=22). Not powered for statistical significance. Pre-DAA era; clinical context has changed. Open-label design potential bias."},{"rthcId":"RPEP-00881","title":"Design, synthesis, biological activity and structural analysis of cyclic peptide inhibitors targeting the substrate recruitment site of cyclin-dependent kinase complexes.","authors":"Andrews, Martin J I; McInnes, Campbell; Kontopidis, George; Innes, Lorraine; Cowan, Angela; Plater, Andy; Fischer, Peter M","year":2004,"journal":"Organic & biomolecular chemistry, 2(19), 2735-41","doi":null,"pmid":"15455144","tags":["cyclic-peptides","cancer","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Cyclic peptides targeting CDK2's substrate recruitment site (not catalytic site) selectively induced tumor cell apoptosis through the E2F pathway, with crystal structures confirming the novel binding mechanism.","whyItMatters":"Cancer-selective cell killing is the holy grail of oncology. Targeting CDK2's substrate site achieves selectivity that conventional kinase inhibitors (which target the active site shared by many kinases) cannot.","specificNumbers":"","methodology":"In-vitro study. Cyclic peptide design, synthesis, and testing for CDK2 substrate recruitment inhibition. Cancer cell apoptosis measured. Crystal structures of peptide-CDK2 complexes determined.","limitations":"In-vitro cancer cell studies. In-vivo efficacy and pharmacokinetics not assessed. Cyclic peptide drug delivery remains challenging."},{"rthcId":"RPEP-00882","title":"The effects of MK-0677, an oral growth hormone secretagogue, in patients with hip fracture.","authors":"Bach, Mark A; Rockwood, Kenneth; Zetterberg, Carl; Thamsborg, Gorm; Hébert, Réjean; Devogelaer, Jean-Pierre; Christiansen, Jens Sandahl; Rizzoli, René; Ochsner, J Lockwood; Beisaw, Norman; Gluck, Oscar; Yu, Leisure; Schwab, Thomas; Farrington, Jeanne; Taylor, Alice M; Ng, Jennifer; Fuh, Vivian","year":2004,"journal":"Journal of the American Geriatrics Society, 52(4), 516-23","doi":null,"pmid":"15066065","tags":["mk-677","bone-joint","hormone-optimization","clinical-trials"],"studyType":"RCT","evidenceStrength":"moderate","keyFinding":"MK-677 increased GH and IGF-1 in elderly hip fracture patients with functional improvement trends, but the primary endpoint of functional independence was not statistically significant in this pilot RCT.","whyItMatters":"Hip fractures are devastating for the elderly — many never regain independence. While MK-677 didn't achieve the primary endpoint, the hormonal effects and safety data support larger studies.","specificNumbers":"","methodology":"Placebo-controlled, randomized, double-blind pilot study. Elderly hip fracture patients received MK-677 or placebo. GH, IGF-1, functional recovery (ADL independence, walking, stair climbing), and safety measured.","limitations":"Pilot study — underpowered for functional endpoints. Elderly hip fracture patients are heterogeneous. The dose and timing may not have been optimal."},{"rthcId":"RPEP-00883","title":"Oxyntomodulin and glucagon-like peptide-1 differentially regulate murine food intake and energy expenditure.","authors":"Baggio, Laurie L; Huang, Qingling; Brown, Theodore J; Drucker, Daniel J","year":2004,"journal":"Gastroenterology, 127(2), 546-58","doi":null,"pmid":"15300587","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00884","title":"The effect of CNS opioid on autonomic nervous and cardiovascular responses in diet-induced obese rats.","authors":"Barnes, Maria J; Jen, K-L Catherine; Dunbar, Joseph C","year":2004,"journal":"Peptides, 25(1), 71-9","doi":null,"pmid":"15003358","tags":["opioid-peptides","cardiovascular","weight-loss"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"ICV beta-endorphin decreased blood pressure in lean rats but increased it in diet-induced obese rats, with enhanced sympathetic activation and reduced vagal tone — demonstrating a fundamental opioid-cardiovascular control reversal in obesity.","whyItMatters":"Obesity-related hypertension kills millions. This study reveals a specific brain mechanism — reversed opioid-cardiovascular signaling — that may drive obesity-related cardiovascular disease.","specificNumbers":"","methodology":"Animal study. ICV beta-endorphin in lean versus diet-induced obese rats. Blood pressure, heart rate, sympathetic and parasympathetic nervous system activity measured.","limitations":"Rat DIO model. The specific neural pathways mediating the reversal were not fully mapped. Human confirmation needed."},{"rthcId":"RPEP-00885","title":"Fat in the intestine as a regulator of appetite--role of CCK.","authors":"Beglinger, Christoph; Degen, Lukas","year":2004,"journal":"Physiology & behavior, 83(4), 617-21","doi":null,"pmid":"15621067","tags":["neuropeptides","weight-loss"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Intestinal fat is the most potent CCK-releasing macronutrient, with CCK mediating fat-induced satiety through vagal afferent and brain pathways — the primary mechanism for the high satiating power of dietary fat.","whyItMatters":"Understanding why fat is so satiating (through CCK) informs dietary strategies for weight management and guides CCK-based drug development for appetite control.","specificNumbers":"","methodology":"Review of human and animal studies on intestinal fat, CCK release, satiety mechanisms, and clinical implications for appetite regulation.","limitations":"Review from 2004. CCK-based obesity treatments have had limited clinical success. The high satiety of fat doesn't prevent overeating in practice due to other factors."},{"rthcId":"RPEP-00886","title":"The influence of gastric pentadecapeptide BPC 157 on acute and chronic ethanol administration in mice.","authors":"Blagaic, Alenka Boban; Blagaic, Vladimir; Romic, Zeljko; Sikiric, Predrag","year":2004,"journal":"European journal of pharmacology, 499(3), 285-90","doi":null,"pmid":"15381050","tags":["bpc-157","addiction","neuroprotection","gut-healing"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"BPC-157 protected against acute ethanol toxicity (reduced mortality, behavioral impairment, gastric damage) and chronic alcohol effects (reduced intake, liver protection), demonstrating comprehensive anti-alcohol therapeutic potential.","whyItMatters":"Alcohol use disorder is a leading cause of preventable death. A peptide that reduces both the desire to drink AND the damage from drinking addresses the complete disease — prevention and treatment.","specificNumbers":"","methodology":"Animal study in mice. Acute ethanol (lethal and sublegal doses): mortality, behavior, gastric lesions measured. Chronic ethanol: voluntary intake, liver pathology, organ damage assessed. BPC-157 at standard doses.","limitations":"Mouse study. Human alcoholism is more complex than mouse ethanol models. The mechanisms of reduced intake and reduced toxicity were not fully characterized."},{"rthcId":"RPEP-00887","title":"Sustained elevation of pulsatile growth hormone (GH) secretion and insulin-like growth factor I (IGF-I), IGF-binding protein-3 (IGFBP-3), and IGFBP-5 concentrations during 30-day continuous subcutaneous infusion of GH-releasing peptide-2 in older men and women.","authors":"Bowers, Cyril Y; Granda, Ramona; Mohan, Subburaman; Kuipers, Jonathan; Baylink, David; Veldhuis, Johannes D","year":2004,"journal":"The Journal of clinical endocrinology and metabolism, 89(5), 2290-300","doi":null,"pmid":"15126555","tags":["ghrp","hormone-optimization","anti-aging"],"studyType":"clinical-trial","evidenceStrength":"strong","keyFinding":"Combined SC GHRP-2 + GHRH infusion sustainably elevated pulsatile GH, IGF-1, and IGFBP-3 in healthy older adults without desensitization, with synergy exceeding individual effects and women showing greater response than men.","whyItMatters":"Age-related GH decline affects millions. A sustained, synergistic peptide combination that restores youthful GH patterns without desensitization could transform anti-aging endocrinology.","specificNumbers":"","methodology":"Clinical trial in healthy older adults. SC infusion of combined GHRP-2 + GHRH. GH profiling (deconvolution analysis), IGF-1, IGFBP-3 measured. Gender comparison. Synergy versus individual peptide effects assessed.","limitations":"Short-term SC infusion study. Long-term chronic infusion effects need assessment. SC infusion is less practical than oral or daily injection dosing."},{"rthcId":"RPEP-00888","title":"The clinical relevance of adrenomedullin: a promising profile?","authors":"Bunton, David C; Petrie, Mark C; Hillier, Chris; Johnston, Fiona; McMurray, John J V","year":2004,"journal":"Pharmacology & therapeutics, 103(3), 179-201","doi":null,"pmid":"15464589","tags":["neuropeptides","cardiovascular","inflammation","kidney"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Adrenomedullin has clinical relevance as both a biomarker (predicting outcomes in sepsis, HF, ACS) and a potential therapeutic (improving hemodynamics, protecting kidneys, reducing inflammation) — a dual biomarker-therapy peptide.","whyItMatters":"AM is rare — a peptide that both MEASURES disease severity and TREATS the disease. This dual role streamlines clinical development from biomarker to therapy.","specificNumbers":"","methodology":"Comprehensive review of adrenomedullin clinical studies covering biomarker applications (sepsis, HF, ACS prognosis) and therapeutic trials (hemodynamic improvement, renal protection).","limitations":"Review from 2004. Clinical therapeutic trials were mostly small. The optimal therapeutic dose and formulation were not established."},{"rthcId":"RPEP-00889","title":"Mice lacking pro-opiomelanocortin are sensitive to high-fat feeding but respond normally to the acute anorectic effects of peptide-YY(3-36).","authors":"Challis, B G; Coll, A P; Yeo, G S H; Pinnock, S B; Dickson, S L; Thresher, R R; Dixon, J; Zahn, D; Rochford, J J; White, A; Oliver, R L; Millington, G; Aparicio, S A; Colledge, W H; Russ, A P; Carlton, M B; O'Rahilly, S","year":2004,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 101(13), 4695-700","doi":null,"pmid":"15070780","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00890","title":"Protective effects of ghrelin on ischemia/reperfusion injury in the isolated rat heart.","authors":"Chang, Lin; Ren, Yongsheng; Liu, Xiuhua; Li, Wei Gen; Yang, Jinghui; Geng, Bin; Weintraub, Neal L; Tang, Chaoshu","year":2004,"journal":"Journal of cardiovascular pharmacology, 43(2), 165-70","doi":null,"pmid":"14716201","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00891","title":"Novel aspects of the renal renin-angiotensin system: angiotensin-(1-7), ACE2 and blood pressure regulation.","authors":"Chappell, Mark C; Modrall, J Gregory; Diz, Debra I; Ferrario, Carlos M","year":2004,"journal":"Contributions to nephrology, 143, 77-89","doi":null,"pmid":"15248357","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00892","title":"Beta-defensins and LL-37 in bronchoalveolar lavage fluid of patients with cystic fibrosis.","authors":"Chen, Christiane I-U; Schaller-Bals, Susanne; Paul, Karl P; Wahn, Ulrich; Bals, Robert","year":2004,"journal":"Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society, 3(1), 45-50","doi":null,"pmid":"15463886","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00893","title":"MicroPET and autoradiographic imaging of breast cancer alpha v-integrin expression using 18F- and 64Cu-labeled RGD peptide.","authors":"Chen, Xiaoyuan; Park, Ryan; Tohme, Michel; Shahinian, Anthony H; Bading, James R; Conti, Peter S","year":2004,"journal":"Bioconjugate chemistry, 15(1), 41-9","doi":null,"pmid":"14733582","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00894","title":"Micro-PET imaging of alphavbeta3-integrin expression with 18F-labeled dimeric RGD peptide.","authors":"Chen, Xiaoyuan; Tohme, Michel; Park, Ryan; Hou, Yingping; Bading, James R; Conti, Peter S","year":2004,"journal":"Molecular imaging, 3(2), 96-104","doi":null,"pmid":"15296674","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00895","title":"Adrenomedullin: its role in the cardiovascular system.","authors":"Cheung, Bernard M Y; Li, Carol Y Y; Wong, Louisa Y F","year":2004,"journal":"Seminars in vascular medicine, 4(2), 129-34","doi":null,"pmid":"15478033","tags":["neuropeptides","cardiovascular"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Adrenomedullin serves as an endogenous cardiovascular protector through vasodilation, cardiac output enhancement, natriuresis, and direct cardioprotection via CRLR/RAMP receptor complexes — a comprehensive cardiovascular defense peptide.","whyItMatters":"Heart failure and hypertension need multiple therapeutic targets. AM provides vasodilation, cardiac protection, AND sodium excretion — three key therapeutic goals from one peptide system.","specificNumbers":"","methodology":"Review of adrenomedullin cardiovascular biology covering production, receptor system, vasodilatory/natriuretic/cardioprotective effects, and clinical implications.","limitations":"Brief review. Therapeutic AM development was still early. Specific clinical trial results were limited."},{"rthcId":"RPEP-00896","title":"Thymalfasin for the treatment of chronic hepatitis B.","authors":"Chien, Rong-Nan; Liaw, Yun-Fan","year":2004,"journal":"Expert review of anti-infective therapy, 2(1), 9-16","doi":null,"pmid":"15482167","tags":["thymosin-alpha-1","infection","immune-function","clinical-trials"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Thymalfasin achieved 25-40% sustained virological response in chronic HBV with response rates increasing over follow-up (unlike interferon relapse), superior safety profile, and durable immune-mediated viral control.","whyItMatters":"Chronic HBV affects 300 million people. A well-tolerated drug with durable responses that improve over time addresses the biggest limitation of existing therapies — treatment durability.","specificNumbers":"","methodology":"Comprehensive drug review covering thymalfasin mechanism (T-cell, NK, DC activation), clinical trial data (monotherapy and combinations), sustained response rates, and safety profile.","limitations":"Review of available trial data through 2004. Some trials had small sample sizes. The mechanism of increasing response over time was not fully explained."},{"rthcId":"RPEP-00897","title":"Ghrelin inhibits FGF-2-mediated angiogenesis in vitro and in vivo.","authors":"Conconi, Maria Teresa; Nico, Beatrice; Guidolin, Diego; Baiguera, Silvia; Spinazzi, Raffaella; Rebuffat, Piera; Malendowicz, Ludwik K; Vacca, Angelo; Carraro, Gianni; Parnigotto, Pier Paolo; Nussdorfer, Gastone G; Ribatti, Domenico","year":2004,"journal":"Peptides, 25(12), 2179-85","doi":null,"pmid":"15572208","tags":["ghrp","cardiovascular"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Ghrelin inhibited FGF-2-mediated angiogenesis: reduced endothelial cell proliferation, migration, tube formation in vitro, and new vessel formation in vivo — demonstrating anti-angiogenic rather than pro-angiogenic activity.","whyItMatters":"Cancer safety was a major concern for GH secretagogues. Finding that ghrelin INHIBITS angiogenesis reverses the feared cancer risk and suggests potential anti-cancer utility.","specificNumbers":"","methodology":"In-vitro: endothelial cell proliferation, migration, and tube formation with FGF-2 ± ghrelin. In-vivo: Matrigel plug angiogenesis assay in mice with FGF-2 ± ghrelin.","limitations":"FGF-2-specific angiogenesis model. Other angiogenic pathways (VEGF) may respond differently. The physiological relevance of ghrelin's anti-angiogenic activity needs in-vivo tumor confirmation."},{"rthcId":"RPEP-00898","title":"Peptide inhibitors of virus-cell fusion: enfuvirtide as a case study in clinical discovery and development.","authors":"Cooper, David A; Lange, Joep M A","year":2004,"journal":"The Lancet. Infectious diseases, 4(7), 426-36","doi":null,"pmid":"15219553","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00899","title":"Alterations in the natriuretic hormone system related to cardiopulmonary bypass in infants with congestive heart failure.","authors":"Costello, J M; Backer, C L; Checchia, P A; Mavroudis, C; Seipelt, R G; Goodman, D M","year":2004,"journal":"Pediatric cardiology, 25(4), 347-53","doi":null,"pmid":"14735254","tags":["natriuretic-peptides","cardiovascular"],"studyType":"cohort","evidenceStrength":"preliminary","keyFinding":"BNP, ANP, and N-terminal ANP showed characteristic perioperative release patterns during infant cardiac surgery, with BNP best correlating with surgical cardiac stress — supporting neonatal/infant cardiac biomarker monitoring.","whyItMatters":"Pediatric cardiac surgery monitoring has fewer tools than adult. Demonstrating natriuretic peptide utility even in infants extends this monitoring capability to the youngest patients.","specificNumbers":"","methodology":"Prospective cohort in 5 infants with CHF undergoing CPB surgery. Serial BNP, ANP, and N-ANP measured pre-op, during bypass, and post-op.","limitations":"Only 5 infants — case series, not definitive. Specific CPB protocols and CHF etiologies may affect peptide patterns."},{"rthcId":"RPEP-00900","title":"The role of the cyclic peptide backbone in the anti-HIV activity of the cyclotide kalata B1.","authors":"Daly, Norelle L; Gustafson, Kirk R; Craik, David J","year":2004,"journal":"FEBS letters, 574(1-3), 69-72","doi":null,"pmid":"15358541","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00901","title":"Biomarkers of satiation and satiety.","authors":"de Graaf, Cees; Blom, Wendy A M; Smeets, Paul A M; Stafleu, Annette; Hendriks, Henk F J","year":2004,"journal":"The American journal of clinical nutrition, 79(6), 946-61","doi":null,"pmid":"15159223","tags":["neuropeptides","weight-loss","glp-1"],"studyType":"review","evidenceStrength":"strong","keyFinding":"CCK and GLP-1 are the most validated satiety biomarkers correlating with both subjective appetite ratings and actual food intake, with PYY, ghrelin, insulin, and glucose providing complementary information in multi-marker panels.","whyItMatters":"Obesity drug development and nutrition research need reliable satiety biomarkers. This review identifies which measurements actually correlate with human appetite and which are just noise.","specificNumbers":"","methodology":"Critical review of studies correlating physiological measures (gut peptides, metabolites, neural signals) with subjective appetite ratings and measured food intake in humans.","limitations":"Review of correlation studies. Correlation between a biomarker and satiety doesn't prove the biomarker drives satiety. Methodological differences between studies complicate comparisons."},{"rthcId":"RPEP-00902","title":"Effect of bovine lactoferricin on enteropathogenic Yersinia adhesion and invasion in HEp-2 cells.","authors":"Di Biase, Assunta Maria; Tinari, Antonella; Pietrantoni, Agostina; Antonini, Giovanni; Valenti, Piera; Conte, Maria Pia; Superti, Fabiana","year":2004,"journal":"Journal of medical microbiology, 53(Pt 5), 407-412","doi":"10.1099/jmm.0.05410-0","pmid":"15096550","tags":["antimicrobial-peptides","infection","gut-healing"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Bovine lactoferricin dose-dependently reduced Yersinia adhesion to and invasion of HEp-2 cells even at sub-bactericidal concentrations, demonstrating anti-virulence activity complementing its bactericidal effects.","whyItMatters":"Preventing bacteria from invading cells is potentially more effective than trying to kill them after infection. This anti-adherence/anti-invasion effect could prevent infection establishment.","specificNumbers":"","methodology":"In-vitro infection study. Bovine lactoferricin at various concentrations incubated with enteropathogenic Yersinia and HEp-2 cells. Adhesion and invasion quantified by gentamicin protection assay.","limitations":"In-vitro cell infection model. The concentrations achievable at intestinal surfaces are uncertain. Single pathogen tested."},{"rthcId":"RPEP-00903","title":"Double-blind, placebo-controlled evaluation of the safety, pharmacokinetic properties and pharmacodynamic effects of intranasal PT-141, a melanocortin receptor agonist, in healthy males and patients with mild-to-moderate erectile dysfunction.","authors":"Diamond, L E; Earle, D C; Rosen, R C; Willett, M S; Molinoff, P B","year":2004,"journal":"International journal of impotence research, 16(1), 51-9","doi":null,"pmid":"14963471","tags":["pt-141","sexual-health","bioavailability","clinical-trials"],"studyType":"RCT","evidenceStrength":"moderate","keyFinding":"Intranasal PT-141 induced dose-dependent erectile responses in both healthy men and Viagra-responsive ED patients in a double-blind, placebo-controlled trial, with rapid onset and acceptable safety — validating intranasal melanocortin ED therapy.","whyItMatters":"PT-141's intranasal delivery offers a non-invasive alternative to injections. Its brain-based mechanism helps patients where Viagra (which works on blood flow) is insufficient — addressing desire, not just mechanics.","specificNumbers":"","methodology":"Double-blind, placebo-controlled, dose-escalation study. PT-141 intranasal spray in healthy males and Viagra-responsive ED patients. Erectile response (RigiScan), pharmacokinetics, and safety measured.","limitations":"Viagra-responsive ED patients (mild ED). Results may differ in severe ED or Viagra-non-responders. Nausea at higher doses limits dose escalation."},{"rthcId":"RPEP-00904","title":"Ghrelin inhibits leptin- and activation-induced proinflammatory cytokine expression by human monocytes and T cells.","authors":"Dixit, Vishwa Deep; Schaffer, Eric M; Pyle, Robert S; Collins, Gary D; Sakthivel, Senthil K; Palaniappan, Ravichandran; Lillard, James W; Taub, Dennis D","year":2004,"journal":"The Journal of clinical investigation, 114(1), 57-66","doi":null,"pmid":"15232612","tags":["ghrp","immune-function","inflammation","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Ghrelin inhibited leptin-induced and activation-induced IL-1β, IL-6, and TNF-α production in human monocytes and T-cells through functional GHS-R on immune cells, establishing an anti-inflammatory role that opposes leptin's pro-inflammatory effects.","whyItMatters":"The ghrelin-leptin opposition extends to inflammation: ghrelin (hungry) suppresses inflammation while leptin (fed) promotes it. This metabolic-immune connection has implications for inflammatory diseases and obesity-related inflammation.","specificNumbers":"","methodology":"In-vitro study. Human monocytes and T-cells treated with ghrelin ± leptin or activation stimuli. Pro-inflammatory cytokine production measured. GHS-R expression on immune cells confirmed.","limitations":"In-vitro immune cell study. The physiological significance of ghrelin's anti-inflammatory effect at circulating concentrations needs in-vivo confirmation."},{"rthcId":"RPEP-00905","title":"Pharmacological characteristics of KP-102 (GHRP-2), a potent growth hormone-releasing peptide.","authors":"Doi, Naomi; Hirotani, Chiharu; Ukai, Kiyoharu; Shimada, Osafumi; Okuno, Tadashi; Kurasaki, Shigeru; Kiyofuji, Takeshi; Ikegami, Reiko; Futamata, Machiko; Nakagawa, Terutake; Ase, Katsuhiko; Chihara, Kazuo","year":2004,"journal":"Arzneimittel-Forschung, 54(12), 857-67","doi":null,"pmid":"15646370","tags":["ghrp","hormone-optimization","receptor-signaling","clinical-trials"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"GHRP-2 (KP-102/pralmorelin) demonstrates potent GH-releasing activity through dual hypothalamic-pituitary mechanisms, with characterized appetite, cardiovascular, and diagnostic applications — a comprehensive pharmacological profile.","whyItMatters":"GHRP-2 is one of the most widely used GH secretagogues in research and clinical testing. This definitive pharmacological reference is essential for anyone working with this compound.","specificNumbers":"","methodology":"Comprehensive pharmacological review covering GHRP-2 receptor binding, in-vitro/in-vivo GH-releasing activity, appetite effects, cardiovascular properties, and clinical trial data.","limitations":"Review from 2004. Some clinical applications were still in development."},{"rthcId":"RPEP-00906","title":"Minireview: Gut peptides regulating satiety.","authors":"Druce, Maralyn R; Small, Caroline J; Bloom, Stephen R","year":2004,"journal":"Endocrinology, 145(6), 2660-5","doi":null,"pmid":"15044353","tags":["glp-1","ghrp","gut-healing","weight-loss"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"At least 8 gut/pancreatic hormones regulate satiety, with GLP-1, PYY, and amylin identified as the most promising therapeutic targets for obesity — with combination therapy suggested for superior outcomes.","whyItMatters":"This review identified GLP-1 as a top therapeutic target years before semaglutide's success. It also predicted combination peptide therapy — validated by tirzepatide (GLP-1/GIP dual agonist).","specificNumbers":"","methodology":"Mini-review of gut peptide satiety regulation covering ghrelin, GLP-1, oxyntomodulin, PYY, CCK, amylin, PP, and bombesin/GRP.","limitations":"Brief review from 2004. The therapeutic hierarchy has shifted since (GLP-1 became dominant). Combination therapy details were speculative."},{"rthcId":"RPEP-00907","title":"alpha-Melanocyte-stimulating hormone, MSH 11-13 KPV and adrenocorticotropic hormone signalling in human keratinocyte cells.","authors":"Elliott, Richard J; Szabo, Marika; Wagner, Mark J; Kemp, E Helen; MacNeil, Sheila; Haycock, John W","year":2004,"journal":"The Journal of investigative dermatology, 122(4), 1010-9","doi":null,"pmid":"15102092","tags":["kpv","inflammation","skin-repair","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"KPV inhibited NF-κB inflammatory signaling in human keratinocytes through a cAMP-independent mechanism, distinct from full-length alpha-MSH's classical cAMP-dependent MC1R signaling.","whyItMatters":"KPV's non-classical mechanism means it works differently from the parent peptide. Understanding this alternative pathway could enable optimization of KPV-based anti-inflammatory therapies for skin.","specificNumbers":"","methodology":"In-vitro study using human keratinocyte HaCaT cells. Alpha-MSH, KPV, and ACTH effects on cAMP levels and NF-κB activation compared. Melanocortin receptor expression characterized.","limitations":"Single keratinocyte cell line (HaCaT). The specific non-cAMP mechanism (direct intracellular entry? alternative receptor?) was not identified."},{"rthcId":"RPEP-00908","title":"Cardiac natriuretic hormones, neuro-hormones, thyroid hormones and cytokines in normal subjects and patients with heart failure.","authors":"Emdin, Michele; Passino, Claudio; Prontera, Concetta; Iervasi, Annalisa; Ripoli, Andrea; Masini, Silvano; Zucchelli, Gian Carlo; Clerico, Aldo","year":2004,"journal":"Clinical chemistry and laboratory medicine, 42(6), 627-36","doi":null,"pmid":"15259379","tags":["natriuretic-peptides","cardiovascular","clinical-trials"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Heart failure involves coordinated dysregulation across natriuretic peptides, catecholamines, endothelin, thyroid hormones, and inflammatory cytokines, with multi-marker profiling providing comprehensive characterization beyond any single biomarker.","whyItMatters":"Understanding heart failure requires a systems perspective. No single marker captures the full picture — multi-marker panels that include peptides, hormones, and cytokines together provide the most complete disease assessment.","specificNumbers":"","methodology":"Cohort study comparing comprehensive neurohormonal profiles (BNP, ANP, noradrenaline, endothelin, thyroid hormones, TNF-α, IL-6) between CHF patients and normal controls.","limitations":"Cross-sectional comparison. The relative contribution of each system to disease progression and treatment response needs longitudinal assessment."},{"rthcId":"RPEP-00909","title":"Effects of Semax on dopaminergic and serotoninergic systems of the brain.","authors":"Eremin, K O; Kudrin, V S; Grivennikov, I A; Miasoedov, N F; Rayevsky, K S","year":2004,"journal":"Doklady biological sciences : proceedings of the Academy of Sciences of the USSR, Biological sciences sections, 394, 1-3","doi":null,"pmid":"15088389","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00910","title":"Dual secretagogue drive of burst-like growth hormone secretion in postmenopausal compared with premenopausal women studied under an experimental estradiol clamp.","authors":"Erickson, Dana; Keenan, Daniel M; Mielke, Kristi; Bradford, Kandace; Bowers, Cyril Y; Miles, John M; Veldhuis, Johannes D","year":2004,"journal":"The Journal of clinical endocrinology and metabolism, 89(9), 4746-54","doi":null,"pmid":"15356089","tags":["ghrp","cjc-1295","hormone-optimization","clinical-trials"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"Postmenopausal women, even with estradiol replacement, showed reduced fasting GH, IGF-1, and diminished dual-secretagogue GH burst response compared to premenopausal women — suggesting irreversible menopausal GH axis changes.","whyItMatters":"If menopause causes irreversible GH axis changes, estrogen replacement alone won't restore youthful GH function. Combined peptide therapy may help but won't fully reverse the age-related decline.","specificNumbers":"","methodology":"Clinical trial comparing postmenopausal (with E2 replacement) and premenopausal women during dual GHRP + GHRH stimulation. GH deconvolution analysis, IGF-1, and burst parameters measured.","limitations":"Estradiol-matched comparison but other menopausal hormonal changes (progesterone, androgens) not controlled. Small sample inherent to intensive GH profiling."},{"rthcId":"RPEP-00911","title":"BNP and ANP as diagnostic and predictive markers in heart failure with left ventricular systolic dysfunction.","authors":"Falcão, Luiz Menezes; Pinto, Fausto; Ravara, Luciano; van Zwieten, Peter Adriaan","year":2004,"journal":"Journal of the renin-angiotensin-aldosterone system : JRAAS, 5(3), 121-9","doi":null,"pmid":"15526247","tags":["natriuretic-peptides","cardiovascular","clinical-trials"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"BNP outperformed ANP for heart failure diagnosis (higher sensitivity/specificity) and prognosis, with NT-proBNP showing particularly strong prognostic value for predicting adverse cardiac events in LV systolic dysfunction.","whyItMatters":"This definitive comparison settles the BNP-vs-ANP debate: BNP/NT-proBNP should be the standard cardiac biomarker for both diagnosis and prognosis in heart failure.","specificNumbers":"","methodology":"Systematic review investigating the diagnostic and prognostic performance of plasma BNP and ANP in heart failure with LV systolic dysfunction across published clinical studies.","limitations":"Systematic review dependent on published study quality. Some studies had small samples or heterogeneous heart failure populations."},{"rthcId":"RPEP-00912","title":"Interactions of lactoferricin-derived peptides with LPS and antimicrobial activity.","authors":"Farnaud, Sebastien; Spiller, Claire; Moriarty, Laura C; Patel, Alpesh; Gant, Vanya; Odell, Edward W; Evans, Robert W","year":2004,"journal":"FEMS microbiology letters, 233(2), 193-9","doi":null,"pmid":"15063486","tags":["antimicrobial-peptides","infection","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Lactoferricin-derived peptides bound bacterial LPS and showed antimicrobial activity against E. coli including LPS mutant strains, with activity correlating with LPS binding — confirming membrane interaction as the killing mechanism.","whyItMatters":"Advances understanding in antimicrobial-peptides, infection, receptor-signaling research.","specificNumbers":"","methodology":"in-vitro study. Details in abstract.","limitations":"See abstract for study-specific limitations."},{"rthcId":"RPEP-00913","title":"Variation in antimicrobial activity of lactoferricin-derived peptides explained by structure modelling.","authors":"Farnaud, Sebastien; Patel, Alpesh; Odell, Edward W; Evans, Robert W","year":2004,"journal":"FEMS microbiology letters, 238(1), 221-6","doi":null,"pmid":"15336425","tags":["antimicrobial-peptides","infection","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Bovine lactoferricin's superior antimicrobial activity versus human lactoferricin was explained by more complete amphipathic beta-sheet formation and denser cationic surface charge distribution, identified through 3D structural modeling.","whyItMatters":"Advances understanding in antimicrobial-peptides, infection, peptide-design research.","specificNumbers":"","methodology":"in-vitro study. Details in abstract.","limitations":"See abstract for study-specific limitations."},{"rthcId":"RPEP-00914","title":"Opioid peptide response to spinal cord stimulation in chronic critical limb ischemia.","authors":"Fontana, Fiorella; Bernardi, Pasquale; Lanfranchi, Giuseppina; Spampinato, Santi; Di Toro, Rosanna; Conti, Eleonora; Bonafè, Francesca; Coccheri, Sergio","year":2004,"journal":"Peptides, 25(4), 571-5","doi":null,"pmid":"15165711","tags":["opioid-peptides","pain","clinical-trials"],"studyType":"clinical-trial","evidenceStrength":"preliminary","keyFinding":"Spinal cord stimulation in chronic critical limb ischemia patients increased CSF beta-endorphin levels, correlating with improved microvascular flow and wound healing — an endogenous opioid mechanism for SCS therapeutic effects.","whyItMatters":"Advances understanding in opioid-peptides, pain, clinical-trials research.","specificNumbers":"","methodology":"clinical-trial study. Details in abstract.","limitations":"See abstract for study-specific limitations."},{"rthcId":"RPEP-00915","title":"Ghrelin: more than a new frontier in neuroendocrinology.","authors":"Ghigo, E; Broglio, F; Me, E; Prodam, F; Ragazzoni, F","year":2004,"journal":"Journal of endocrinological investigation, 27(6 Suppl), 101-4","doi":null,"pmid":"15481809","tags":["ghrp","hormone-optimization","neuropeptides"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Ghrelin's biological roles expanded to include immune modulation (anti-inflammatory), reproductive function, cancer cell growth regulation, and cardiovascular protection through GHS-R and non-GHS-R pathways.","whyItMatters":"Advances understanding in ghrp, hormone-optimization, neuropeptides research.","specificNumbers":"","methodology":"review study. Details in abstract.","limitations":"See abstract for study-specific limitations."},{"rthcId":"RPEP-00916","title":"Ghrelin: a link between eating disorders, obesity and reproduction.","authors":"Gottero, C; Broglio, F; Prodam, F; Destefanis, S; Bellone, S; Benso, A; Gauna, C; Arvat, E; van der Lely, A J; Ghigo, E","year":2004,"journal":"Nutritional neuroscience, 7(5-6), 255-70","doi":null,"pmid":"15682922","tags":["ghrp","weight-loss","fertility","hormone-optimization"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Ghrelin's integrated control of appetite, adiposity, and GnRH/gonadotropin secretion links eating disorders, obesity, and reproductive dysfunction through a common hormonal mechanism.","whyItMatters":"Advances understanding in ghrp, weight-loss, fertility, hormone-optimization research.","specificNumbers":"","methodology":"review study. Details in abstract.","limitations":"See abstract for study-specific limitations."},{"rthcId":"RPEP-00917","title":"Anti-HIV cyclotides.","authors":"Gustafson, Kirk R; McKee, Tawnya C; Bokesch, Heidi R","year":2004,"journal":"Current protein & peptide science, 5(5), 331-40","doi":null,"pmid":"15544529","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00918","title":"Natriuretic peptides and the prevalence of congestive heart failure in patients with pacemakers.","authors":"Gwechenberger, M; Huelsmann, M; Graf, S; Berger, R; Bonderman, D; Stanek, B; Rauscha, F; Pacher, R","year":2004,"journal":"European journal of clinical investigation, 34(12), 811-7","doi":null,"pmid":"15606723","tags":["natriuretic-peptides","cardiovascular","clinical-trials"],"studyType":"cross-sectional","evidenceStrength":"moderate","keyFinding":"Natriuretic peptide levels identified LV dysfunction and comorbidities in pacemaker patients, supporting BNP measurement for detecting subclinical heart failure in cardiac device populations.","whyItMatters":"Advances understanding in natriuretic-peptides, cardiovascular, clinical-trials research.","specificNumbers":"","methodology":"cross-sectional study. Details in abstract.","limitations":"See abstract for study-specific limitations."},{"rthcId":"RPEP-00919","title":"Peptide YY3-36 inhibits food intake in mice through a melanocortin-4 receptor-independent mechanism.","authors":"Halatchev, Ilia G; Ellacott, Kate L J; Fan, Wei; Cone, Roger D","year":2004,"journal":"Endocrinology, 145(6), 2585-90","doi":null,"pmid":"15016721","tags":["neuropeptides","weight-loss","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"PYY3-36 inhibited food intake in MC4R knockout mice, demonstrating a melanocortin-4 receptor-independent satiety mechanism and establishing PYY as an independent appetite-suppressing pathway from the alpha-MSH system.","whyItMatters":"Advances understanding in neuropeptides, weight-loss, receptor-signaling research.","specificNumbers":"","methodology":"animal-study study. Details in abstract.","limitations":"See abstract for study-specific limitations."},{"rthcId":"RPEP-00920","title":"Novel analogs of ghrelin: physiological and clinical implications.","authors":"Halem, Heather A; Taylor, John E; Dong, Jesse Z; Shen, Yeelana; Datta, Rakesh; Abizaid, Alfonso; Diano, Sabrina; Horvath, Tamas; Zizzari, Philippe; Bluet-Pajot, Marie-Thèrèse; Epelbaum, Jacques; Culler, Michael D","year":2004,"journal":"European journal of endocrinology, 151 Suppl 1, S71-5","doi":null,"pmid":"15339248","tags":["ghrp","peptide-design","bioavailability"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Multiple novel ghrelin analogs were designed with improved pharmacokinetic properties (longer half-life, better stability) and selectivity profiles compared to native ghrelin, maintaining GH-releasing and appetite effects in animal models.","whyItMatters":"Advances understanding of ghrp, peptide-design, bioavailability with translational implications.","specificNumbers":"","methodology":"animal-study study examining ghrp and peptide-design.","limitations":"Study-specific limitations apply; see abstract for details."},{"rthcId":"RPEP-00921","title":"The pharmacology of human appetite expression.","authors":"Halford, Jason C G; Cooper, Gillian D; Dovey, Terence M","year":2004,"journal":"Current drug targets, 5(3), 221-40","doi":null,"pmid":"15058309","tags":["glp-1","neuropeptides","weight-loss","receptor-signaling"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Human appetite is regulated by a multi-level system including adiposity signals (leptin, insulin), gut peptides (GLP-1, PYY, CCK, ghrelin), and hypothalamic neuropeptides (NPY, AgRP, POMC), with GLP-1 and PYY identified as the most druggable targets.","whyItMatters":"Advances understanding of glp-1, neuropeptides, weight-loss, receptor-signaling with translational implications.","specificNumbers":"","methodology":"review study examining glp-1 and neuropeptides.","limitations":"Study-specific limitations apply; see abstract for details."},{"rthcId":"RPEP-00922","title":"Acupuncture and endorphins.","authors":"Han, Ji-Sheng","year":2004,"journal":"Neuroscience letters, 361(1-3), 258-61","doi":null,"pmid":"15135942","tags":["opioid-peptides","pain","receptor-signaling"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Acupuncture and electroacupuncture produce analgesia through frequency-specific release of endogenous opioid peptides: low frequency releases endorphins/enkephalins (mu/delta) and high frequency releases dynorphins (kappa), confirmed across animal and human studies.","whyItMatters":"Advances understanding of opioid-peptides, pain, receptor-signaling with translational implications.","specificNumbers":"","methodology":"review study examining opioid-peptides and pain.","limitations":"Study-specific limitations apply; see abstract for details."},{"rthcId":"RPEP-00923","title":"Vagal stimulation exaggerates the inhibitory ghrelin response to oral fat in humans.","authors":"Heath, R B; Jones, R; Frayn, K N; Robertson, M D","year":2004,"journal":"The Journal of endocrinology, 180(2), 273-81","doi":null,"pmid":"14765979","tags":["ghrp","gut-healing","weight-loss","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Vagal stimulation amplified the inhibitory ghrelin response to oral fat in a human/animal model, demonstrating the vagus nerve acts as a gain controller for fat-induced ghrelin suppression — the gut-brain communication amplifying satiety.","whyItMatters":"Advances understanding of ghrp, gut-healing, weight-loss, receptor-signaling with translational implications.","specificNumbers":"","methodology":"animal-study study examining ghrp and gut-healing.","limitations":"Study-specific limitations apply; see abstract for details."},{"rthcId":"RPEP-00924","title":"PT-141 Palatin.","authors":"Hedlund, Petter","year":2004,"journal":"Current opinion in investigational drugs (London, England : 2000), 5(4), 456-62","doi":null,"pmid":"15134289","tags":["pt-141","sexual-health","clinical-trials","receptor-signaling"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"PT-141 intranasal demonstrated ED treatment efficacy in clinical trials through central melanocortin receptor activation, with development progressing toward potential approval as a first-in-class brain-acting sexual dysfunction therapy.","whyItMatters":"Advances understanding of pt-141, sexual-health, clinical-trials, receptor-signaling with translational implications.","specificNumbers":"","methodology":"review study examining pt-141 and sexual-health.","limitations":"Study-specific limitations apply; see abstract for details."},{"rthcId":"RPEP-00925","title":"Peripheral and central signals in the control of eating in normal, obese and binge-eating human subjects.","authors":"Hellström, Per M; Geliebter, Allan; Näslund, Erik; Schmidt, Peter T; Yahav, Eric K; Hashim, Sami A; Yeomans, Martin R","year":2004,"journal":"The British journal of nutrition, 92 Suppl 1, S47-57","doi":null,"pmid":"15384323","tags":["glp-1","neuropeptides","weight-loss","receptor-signaling"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Normal, obese, and binge-eating individuals show distinct patterns of appetite signal dysfunction across peripheral (gut peptides, adipokines) and central (hypothalamic neuropeptide) systems — disorder-specific signaling profiles enabling targeted treatment.","whyItMatters":"Advances understanding of glp-1, neuropeptides, weight-loss, receptor-signaling with translational implications.","specificNumbers":"","methodology":"review study examining glp-1 and neuropeptides.","limitations":"Study-specific limitations apply; see abstract for details."},{"rthcId":"RPEP-00926","title":"Distribution of methionine and leucine enkephalin neurons within the social behavior circuitry of the male Syrian hamster brain.","authors":"Holt, Avril Genene; Newman, Sarah Winans","year":2004,"journal":"Brain research, 1030(1), 28-48","doi":null,"pmid":"15567335","tags":["opioid-peptides","neuropeptides","anxiety-mood"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Met- and leu-enkephalin immunoreactive neurons were distributed throughout social behavior brain nuclei (BNST, medial amygdala, MPOA, lateral septum, PAG) in male hamsters, providing an anatomical framework for opioid peptide regulation of social and reproductive behaviors.","whyItMatters":"Advances understanding of opioid-peptides, neuropeptides, anxiety-mood with translational implications.","specificNumbers":"","methodology":"animal-study study examining opioid-peptides and neuropeptides.","limitations":"Study-specific limitations apply; see abstract for details."},{"rthcId":"RPEP-00927","title":"Macrocyclic inhibitors for peptide deformylase: a structure-activity relationship study of the ring size.","authors":"Hu, Xubo; Nguyen, Kiet T; Jiang, Vernon C; Lofland, Denene; Moser, Heinz E; Pei, Dehua","year":2004,"journal":"Journal of medicinal chemistry, 47(20), 4941-9","doi":null,"pmid":"15369398","tags":["cyclic-peptides","infection","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Ring size optimization of macrocyclic peptide deformylase inhibitors identified the most potent macrocycle dimensions, with X-ray crystallography confirming optimal binding geometry — advancing this bacteria-selective antibiotic mechanism.","whyItMatters":"Advances understanding of cyclic-peptides, infection, peptide-design with translational implications.","specificNumbers":"","methodology":"in-vitro study examining cyclic-peptides and infection.","limitations":"Study-specific limitations apply; see abstract for details."},{"rthcId":"RPEP-00928","title":"Growth hormone releasing peptide (ghrelin) is synthesized and secreted by cardiomyocytes.","authors":"Iglesias, María J; Piñeiro, Roberto; Blanco, Montserrat; Gallego, Rosalía; Diéguez, Carlos; Gualillo, Oreste; González-Juanatey, José R; Lago, Francisca","year":2004,"journal":"Cardiovascular research, 62(3), 481-8","doi":null,"pmid":"15158140","tags":["ghrp","cardiovascular","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Cardiomyocytes expressed ghrelin mRNA and protein, secreted ghrelin into culture medium, and expressed functional GHS-R — establishing an autocrine/paracrine cardiac ghrelin system for local cardiac regulation and protection.","whyItMatters":"Advances understanding of ghrp, cardiovascular, receptor-signaling with translational implications.","specificNumbers":"","methodology":"in-vitro study examining ghrp and cardiovascular.","limitations":"Study-specific limitations apply; see abstract for details."},{"rthcId":"RPEP-00929","title":"Activation of somatostatin-receptor subtype-2/-5 suppresses the mass, frequency, and irregularity of growth hormone (GH)-releasing peptide-2-stimulated GH secretion in men.","authors":"Iranmanesh, Ali; Bowers, Cyril Y; Veldhuis, Johannes D","year":2004,"journal":"The Journal of clinical endocrinology and metabolism, 89(9), 4581-7","doi":null,"pmid":"15356066","tags":["ghrp","hormone-optimization","receptor-signaling","clinical-trials"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"SST2/SST5 receptor activation differentially suppressed GHRH-stimulated and GHRP-2-stimulated GH secretion patterns in healthy men, with different effects on GH mass, frequency, and regularity — revealing receptor-specific modulation of the two GH-releasing pathways.","whyItMatters":"Advances understanding of ghrp, hormone-optimization, receptor-signaling, clinical-trials with translational implications.","specificNumbers":"","methodology":"clinical-trial study examining ghrp and hormone-optimization.","limitations":"Study-specific limitations apply; see abstract for details."},{"rthcId":"RPEP-00930","title":"Blockade of endogenous growth hormone-releasing hormone receptors dissociates nocturnal growth hormone secretion and slow-wave sleep.","authors":"Jessup, Stacy K; Malow, Beth A; Symons, Kathleen V; Barkan, Ariel L","year":2004,"journal":"European journal of endocrinology, 151(5), 561-6","doi":null,"pmid":"15538933","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00931","title":"The electrophysiology of feeding circuits.","authors":"Jobst, Erin E; Enriori, Pablo J; Cowley, Michael A","year":2004,"journal":"Trends in endocrinology and metabolism: TEM, 15(10), 488-99","doi":null,"pmid":"15541648","tags":["neuropeptides","weight-loss","receptor-signaling"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Hypothalamic feeding circuits operate through electrophysiological excitation of NPY/AgRP neurons (hunger) and inhibition of POMC/CART neurons (satiety), with peripheral signals (ghrelin, leptin, insulin) directly modulating neuronal firing patterns.","whyItMatters":"Advances understanding of neuropeptides, weight-loss, receptor-signaling.","specificNumbers":"","methodology":"review study examining neuropeptides and weight-loss.","limitations":"Study-specific limitations; see abstract."},{"rthcId":"RPEP-00932","title":"The influence of opioid peptides on steroidogenesis in porcine granulosa cells.","authors":"Kaminski, T; Siawrys, C; Bogacka, I; Okrasa, S; Przala, J","year":2004,"journal":"Reproduction in domestic animals = Zuchthygiene, 39(1), 25-32","doi":null,"pmid":"15129917","tags":["opioid-peptides","fertility","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Opioid peptides differentially modulated granulosa cell steroidogenesis: inhibiting progesterone while stimulating estradiol through kappa and mu receptor subtypes, revealing a complex opioid regulatory layer in ovarian hormone production.","whyItMatters":"Advances understanding of opioid-peptides, fertility, receptor-signaling.","specificNumbers":"","methodology":"in-vitro study examining opioid-peptides and fertility.","limitations":"Study-specific limitations; see abstract."},{"rthcId":"RPEP-00933","title":"Peptide promotes overcoming of the division limit in human somatic cell.","authors":"Khavinson, V Kh; Bondarev, I E; Butyugov, A A; Smirnova, T D","year":2004,"journal":"Bulletin of experimental biology and medicine, 137(5), 503-6","doi":null,"pmid":"15455129","tags":["anti-aging","peptide-design","immune-function"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Epithalon peptide treatment enabled human somatic cells to overcome the Hayflick division limit (normally ~50 divisions), extending replicative lifespan through telomerase activation and telomere maintenance.","whyItMatters":"Advances understanding of anti-aging, peptide-design, immune-function.","specificNumbers":"","methodology":"in-vitro study examining anti-aging and peptide-design.","limitations":"Study-specific limitations; see abstract."},{"rthcId":"RPEP-00934","title":"Effects of dynamic compressive loading on chondrocyte biosynthesis in self-assembling peptide scaffolds.","authors":"Kisiday, John D; Jin, Moonsoo; DiMicco, Michael A; Kurz, Bodo; Grodzinsky, Alan J","year":2004,"journal":"Journal of biomechanics, 37(5), 595-604","doi":null,"pmid":"15046988","tags":["peptide-design","bone-joint","bioavailability"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Dynamic compressive loading of chondrocytes in self-assembling peptide scaffolds maintained or enhanced cartilage matrix (proteoglycan, collagen) production, demonstrating the scaffold's suitability for the mechanically demanding joint environment.","whyItMatters":"Advances understanding of peptide-design, bone-joint, bioavailability.","specificNumbers":"","methodology":"in-vitro study examining peptide-design and bone-joint.","limitations":"Study-specific limitations; see abstract."},{"rthcId":"RPEP-00935","title":"Brain-gut axis and its role in the control of food intake.","authors":"Konturek, S J; Konturek, J W; Pawlik, T; Brzozowski, T","year":2004,"journal":"Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 55(1 Pt 2), 137-54","doi":null,"pmid":"15082874","tags":["glp-1","ghrp","neuropeptides","gut-healing","weight-loss"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Food intake control operates through an integrated brain-gut axis where peripheral peptides (GLP-1, PYY, CCK, ghrelin, amylin) signal via vagal and hormonal routes to central circuits (NPY/AgRP, POMC/CART, CRF) for coordinated appetite regulation.","whyItMatters":"Advances understanding of glp-1, ghrp, neuropeptides, gut-healing, weight-loss.","specificNumbers":"","methodology":"review study examining glp-1 and ghrp.","limitations":"Study-specific limitations; see abstract."},{"rthcId":"RPEP-00936","title":"Ghrelin--a hormone with multiple functions.","authors":"Korbonits, Márta; Goldstone, Anthony P; Gueorguiev, Maria; Grossman, Ashley B","year":2004,"journal":"Frontiers in neuroendocrinology, 25(1), 27-68","doi":null,"pmid":"15183037","tags":["ghrp","hormone-optimization","cardiovascular","weight-loss","immune-function"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Ghrelin demonstrates validated multi-system functions: GH release, appetite/adiposity control, cardiovascular protection, immune modulation, gastric motility regulation, and reproductive function — through GHS-R and non-GHS-R pathways in virtually every organ system.","whyItMatters":"Advances understanding of ghrp, hormone-optimization, cardiovascular, weight-loss, immune-function.","specificNumbers":"","methodology":"review study examining ghrp and hormone-optimization.","limitations":"Study-specific limitations; see abstract."},{"rthcId":"RPEP-00937","title":"Molecular evolution of NPY receptor subtypes.","authors":"Larhammar, D; Salaneck, E","year":2004,"journal":"Neuropeptides, 38(4), 141-51","doi":null,"pmid":"15337367","tags":["neuropeptides","receptor-signaling","peptide-design"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"NPY receptor subtypes Y1-Y5 evolved through ancient gene duplications, with each acquiring distinct tissue distribution and functional specialization — Y1 for anxiety/vasoconstriction, Y2 for presynaptic inhibition, Y4 for PP binding, Y5 for feeding.","whyItMatters":"Advances understanding of neuropeptides, receptor-signaling, peptide-design.","specificNumbers":"","methodology":"review study examining neuropeptides and receptor-signaling.","limitations":"Study-specific limitations; see abstract."},{"rthcId":"RPEP-00938","title":"Prediction of antibiotic activity and synthesis of new pentadecapeptides based on lactoferricins.","authors":"Lejon, Tore; Stiberg, Trine; Strøm, Morten B; Svendsen, John S","year":2004,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 10(6), 329-35","doi":null,"pmid":"15214437","tags":["antimicrobial-peptides","infection","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Novel pentadecapeptides designed by computational prediction from lactoferricin's activity features demonstrated real antibacterial activity against test organisms, validating in-silico antimicrobial peptide design approaches.","whyItMatters":"Advances understanding of antimicrobial-peptides, infection, peptide-design.","specificNumbers":"","methodology":"in-vitro study examining antimicrobial-peptides and infection.","limitations":"Study-specific limitations; see abstract."},{"rthcId":"RPEP-00939","title":"The neuroprotective effects of Semax in conditions of MPTP-induced lesions of the brain dopaminergic system.","authors":"Levitskaya, N G; Sebentsova, E A; Andreeva, L A; Alfeeva, L Yu; Kamenskii, A A; Myasoedov, N F","year":2004,"journal":"Neuroscience and behavioral physiology, 34(4), 399-405","doi":null,"pmid":"15341218","tags":["semax","neuroprotective-peptides","Parkinsons-disease","ACTH-analogs"],"studyType":"animal","evidenceStrength":"preliminary","keyFinding":"Daily intranasal administration of Semax (an ACTH(4-10) analog peptide, sequence MEHFPGP) at 0.2 mg/kg reduced the severity of behavioral disturbances caused by the neurotoxin MPTP in rats. MPTP selectively destroys dopamine neurons — the same neurons lost in Parkinson's disease — causing decreased movement and increased anxiety. Semax treatment lessened both of these deficits.\n\nThe researchers proposed two mechanisms for Semax's protective effects: direct modulation of the dopaminergic system and broader neurotrophic (nerve-supporting) activity of the peptide.","whyItMatters":"Parkinson's disease is caused by the progressive loss of dopamine-producing neurons, and there are currently no treatments that slow this process. Semax is a synthetic peptide developed in Russia that has shown neuroprotective properties in various models. This study suggests it may specifically protect the dopaminergic system — the exact pathway that fails in Parkinson's — though much more research would be needed to translate this to human treatment.","specificNumbers":"MPTP dose: 25 mg/kg single i.p. injection · Semax dose: 0.2 mg/kg daily intranasal · Reduced movement deficits · Reduced anxiety behaviors","methodology":"Animal study in white rats. MPTP neurotoxin was administered as a single intraperitoneal injection at 25 mg/kg to create dopaminergic system lesions (a standard Parkinson's disease model). Semax was given daily via intranasal administration at 0.2 mg/kg. Behavioral outcomes including movement activity and anxiety were assessed.","limitations":"Rat study with limited translational certainty to human Parkinson's disease. The MPTP model produces acute dopaminergic damage rather than the progressive neurodegeneration seen in actual Parkinson's. Small study with no specified sample size in the abstract. Published in 2004 with no subsequent large-scale follow-up on this specific application. Semax is primarily used in Russia and not widely studied in Western clinical settings."},{"rthcId":"RPEP-00940","title":"Ghrelin inhibits proinflammatory responses and nuclear factor-kappaB activation in human endothelial cells.","authors":"Li, Wei Gen; Gavrila, Dan; Liu, Xuebo; Wang, Lixing; Gunnlaugsson, Skuli; Stoll, Lynn L; McCormick, Michael L; Sigmund, Curt D; Tang, Chaosu; Weintraub, Neal L","year":2004,"journal":"Circulation, 109(18), 2221-6","doi":null,"pmid":"15117840","tags":["ghrp","cardiovascular","inflammation","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Ghrelin inhibited TNF-α-induced VCAM-1, ICAM-1, and MCP-1 expression in human endothelial cells by blocking NF-κB nuclear translocation via IκBα preservation — a specific anti-inflammatory mechanism protecting blood vessels from atherosclerosis.","whyItMatters":"Advances understanding of ghrp, cardiovascular, inflammation, receptor-signaling.","specificNumbers":"","methodology":"in-vitro study examining ghrp and cardiovascular.","limitations":"Study-specific limitations; see abstract."},{"rthcId":"RPEP-00941","title":"Thymalfasin (thymosin-alpha 1) therapy in patients with chronic hepatitis B.","authors":"Liaw, Yun-Fan","year":2004,"journal":"Journal of gastroenterology and hepatology, 19(12), S73-5","doi":null,"pmid":"15641208","tags":["thymosin-alpha-1","infection","immune-function","clinical-trials"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Thymalfasin achieved sustained HBV virological response with increasing durability over follow-up and minimal side effects, positioning it as a well-tolerated immune-based alternative for chronic hepatitis B treatment.","whyItMatters":"Relevant for thymosin-alpha-1, infection, immune-function, clinical-trials.","specificNumbers":"","methodology":"review study on thymosin-alpha-1, infection.","limitations":"See abstract."},{"rthcId":"RPEP-00942","title":"Regulation of ghrelin gene expression in stomach and feeding response to a ghrelin analogue in two strains of rats.","authors":"Liu, Xiaotuan; York, David A; Bray, George A","year":2004,"journal":"Peptides, 25(12), 2171-7","doi":null,"pmid":"15572207","tags":["ghrp","weight-loss","hormone-optimization","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Gastric ghrelin gene expression regulation and feeding response to ghrelin analog differed between lean (Fischer 344) and obesity-prone (Sprague-Dawley) rats, demonstrating genetic/strain variability in ghrelin biology.","whyItMatters":"Relevant for ghrp, weight-loss, hormone-optimization, receptor-signaling.","specificNumbers":"","methodology":"animal-study study on ghrp, weight-loss.","limitations":"See abstract."},{"rthcId":"RPEP-00943","title":"Lactoferricin influences early events of Listeria monocytogenes infection in THP-1 human macrophages.","authors":"Longhi, Catia; Conte, Maria P; Penta, Michela; Cossu, Alessia; Antonini, Giovanni; Superti, Fabiana; Seganti, Lucilla","year":2004,"journal":"Journal of medical microbiology, 53(Pt 2), 87-91","doi":"10.1099/jmm.0.05367-0","pmid":"14729926","tags":["antimicrobial-peptides","infection","immune-function"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Lactoferricin inhibited Listeria monocytogenes adhesion to and internalization by THP-1 human macrophages, reducing early infection events beyond direct bacterial killing — demonstrating anti-virulence protection.","whyItMatters":"Relevant for antimicrobial-peptides, infection, immune-function.","specificNumbers":"","methodology":"in-vitro study on antimicrobial-peptides, infection.","limitations":"See abstract."},{"rthcId":"RPEP-00944","title":"Doxorubicine-congestive heart failure-increased big endothelin-1 plasma concentration: reversal by amlodipine, losartan, and gastric pentadecapeptide BPC157 in rat and mouse.","authors":"Lovric-Bencic, Martina; Sikiric, Predrag; Hanzevacki, Jadranka S; Seiwerth, Sven; Rogic, Dunja; Kusec, Vesna; Aralica, Gorana; Konjevoda, Pasko; Batelja, Lovorka; Blagaic, Alenka B","year":2004,"journal":"Journal of pharmacological sciences, 95(1), 19-26","doi":null,"pmid":"15153646","tags":["bpc-157","cardiovascular","inflammation"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"BPC-157 reversed doxorubicin-induced CHF signs and normalized elevated Big Endothelin-1 levels in rats, comparable to amlodipine and losartan — demonstrating cardioprotective peptide activity against chemotherapy-induced cardiomyopathy.","whyItMatters":"Relevant for bpc-157, cardiovascular, inflammation.","specificNumbers":"","methodology":"animal-study study on bpc-157, cardiovascular.","limitations":"See abstract."},{"rthcId":"RPEP-00945","title":"Human milk proteins: key components for the biological activity of human milk.","authors":"Lönnerdal, Bo","year":2004,"journal":"Advances in experimental medicine and biology, 554, 11-25","doi":null,"pmid":"15384564","tags":["antimicrobial-peptides","immune-function","bioactive-food-peptides","infection"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Human milk proteins (lactoferrin, lysozyme, sIgA, alpha-lactalbumin) and their digestion-generated bioactive peptides provide comprehensive antimicrobial, immunomodulatory, and trophic activities that protect and develop infant health.","whyItMatters":"Relevant for antimicrobial-peptides, immune-function, bioactive-food-peptides, infection.","specificNumbers":"","methodology":"review study on antimicrobial-peptides, immune-function.","limitations":"See abstract."},{"rthcId":"RPEP-00946","title":"Maternal separation alters maternal care, but has minor effects on behavior and brain opioid peptides in adult offspring.","authors":"Marmendal, Maarit; Roman, Erika; Eriksson, C J Peter; Nylander, Ingrid; Fahlke, Claudia","year":2004,"journal":"Developmental psychobiology, 45(3), 140-52","doi":null,"pmid":"15505796","tags":["opioid-peptides","anxiety-mood","addiction","neuropeptides"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Maternal separation significantly altered maternal care patterns but produced only subtle changes in adult offspring brain opioid peptides and behavior, suggesting compensatory mechanisms partially buffer against early-life adversity effects.","whyItMatters":"Relevant for opioid-peptides, anxiety-mood, addiction, neuropeptides.","specificNumbers":"","methodology":"animal-study study on opioid-peptides, anxiety-mood.","limitations":"See abstract."},{"rthcId":"RPEP-00947","title":"Ghrelin enhances the growth of cultured human adrenal zona glomerulosa cells by exerting MAPK-mediated proliferogenic and antiapoptotic effects.","authors":"Mazzocchi, Giuseppina; Neri, Giuliano; Rucinski, Marcin; Rebuffat, Piera; Spinazzi, Raffaella; Malendowicz, Ludwik K; Nussdorfer, Gastone G","year":2004,"journal":"Peptides, 25(8), 1269-77","doi":null,"pmid":"15350694","tags":["ghrp","hormone-optimization","cancer","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Ghrelin stimulated human adrenal zona glomerulosa cell proliferation via p42/p44 MAPK activation and simultaneously inhibited apoptosis through functional GHS-R — dual proliferogenic and anti-apoptotic adrenal effects.","whyItMatters":"Relevant for ghrp, hormone-optimization, cancer, receptor-signaling.","specificNumbers":"","methodology":"in-vitro study on ghrp, hormone-optimization.","limitations":"See abstract."},{"rthcId":"RPEP-00948","title":"Plasma ghrelin concentrations are decreased in insulin-resistant obese adults relative to equally obese insulin-sensitive controls.","authors":"McLaughlin, Tracey; Abbasi, Fahim; Lamendola, Cindy; Frayo, R Scott; Cummings, David E","year":2004,"journal":"The Journal of clinical endocrinology and metabolism, 89(4), 1630-5","doi":null,"pmid":"15070922","tags":["ghrelin","insulin-resistance"],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"Among equally obese adults (BMI ~32), those who were insulin-resistant had significantly lower ghrelin levels (252 pg/ml) than insulin-sensitive individuals (412 pg/ml; P<0.001) — a 39% difference. This finding separates the effect of insulin resistance from obesity itself on ghrelin suppression.\n\nGhrelin correlated inversely with both insulin resistance (r = -0.64; P<0.001) and fasting insulin levels (r = -0.58; P<0.001). Multivariate analysis confirmed that both insulin resistance and high insulin levels independently predicted low ghrelin, suggesting that insulin resistance — not just being overweight — drives ghrelin suppression. This points to a metabolic feedback loop where insulin resistance further suppresses the hunger hormone, potentially disrupting normal appetite regulation.","whyItMatters":"Ghrelin is the body's main hunger signal, and it's known to be lower in obese people. But this study showed that it's not just about being overweight — insulin resistance independently suppresses ghrelin even further. This has important implications for understanding why metabolically unhealthy obese individuals may have disrupted appetite signaling, and it suggests that the insulin-ghrelin connection could be a key piece of the obesity puzzle.","specificNumbers":"","methodology":"Researchers used steady-state plasma glucose concentrations (a gold-standard measure of insulin sensitivity) to identify 20 insulin-resistant and 20 insulin-sensitive obese individuals who were matched for BMI (~32 kg/m²). They measured fasting ghrelin and insulin levels and performed multivariate analysis to determine whether insulin resistance and hyperinsulinemia independently predicted ghrelin suppression after controlling for body weight.","limitations":"This is a cross-sectional observational study — it shows correlation, not causation. The sample is relatively small (40 participants). The study measured fasting ghrelin only, not the dynamic ghrelin response to meals. It cannot determine whether low ghrelin causes further metabolic dysfunction or is merely a consequence of insulin resistance."},{"rthcId":"RPEP-00949","title":"Angiotensin I-converting enzyme inhibitory activity of peptides derived from egg white proteins by enzymatic hydrolysis.","authors":"Miguel, M; Recio, I; Gómez-Ruiz, J A; Ramos, M; López-Fandiño, R","year":2004,"journal":"Journal of food protection, 67(9), 1914-20","doi":null,"pmid":"15453581","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00950","title":"Gastrointestinal satiety signals II. Cholecystokinin.","authors":"Moran, Timothy H; Kinzig, Kimberly P","year":2004,"journal":"American journal of physiology. Gastrointestinal and liver physiology, 286(2), G183-8","doi":null,"pmid":"14715515","tags":["neuropeptides","gut-healing","weight-loss","receptor-signaling"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"CCK released by intestinal fat/protein is the primary short-term satiety signal, acting through vagal afferents and brain CCK-A receptors to reduce meal size — the best-characterized gut satiety peptide with therapeutic implications for obesity.","whyItMatters":"Relevant for neuropeptides, gut-healing, weight-loss, receptor-signaling.","specificNumbers":"","methodology":"review study on neuropeptides, gut-healing.","limitations":"See abstract."},{"rthcId":"RPEP-00951","title":"Ghrelin and des-acyl ghrelin both inhibit isoproterenol-induced lipolysis in rat adipocytes via a non-type 1a growth hormone secretagogue receptor.","authors":"Muccioli, Giampiero; Pons, Nicoletta; Ghè, Corrado; Catapano, Filomena; Granata, Riccarda; Ghigo, Ezio","year":2004,"journal":"European journal of pharmacology, 498(1-3), 27-35","doi":null,"pmid":"15363972","tags":["ghrp","weight-loss","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Both ghrelin forms inhibited isoproterenol-induced lipolysis in rat adipocytes, with the effect NOT mediated by GHS-R1a (des-acyl ghrelin was equally effective) — demonstrating fat metabolism regulation through an unidentified non-GHS-R receptor.","whyItMatters":"Relevant for ghrp, weight-loss, receptor-signaling.","specificNumbers":"","methodology":"in-vitro study on ghrp, weight-loss.","limitations":"See abstract."},{"rthcId":"RPEP-00952","title":"Effects of ghrelin administration on left ventricular function, exercise capacity, and muscle wasting in patients with chronic heart failure.","authors":"Nagaya, Noritoshi; Moriya, Junji; Yasumura, Yoshio; Uematsu, Masaaki; Ono, Fumiaki; Shimizu, Wataru; Ueno, Kazuyuki; Kitakaze, Masafumi; Miyatake, Kunio; Kangawa, Kenji","year":2004,"journal":"Circulation, 110(24), 3674-9","doi":null,"pmid":"15569841","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00953","title":"Conformational analysis of opioid peptides in the solid states and the membrane environments by NMR spectroscopy.","authors":"Naito, Aira; Nishimura, Katsuyuki","year":2004,"journal":"Current topics in medicinal chemistry, 4(1), 135-45","doi":null,"pmid":"14754381","tags":["opioid-peptides","peptide-design","receptor-signaling"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Opioid peptide conformations in membrane-mimetic environments differed significantly from solution structures, revealing the biologically relevant receptor-interacting conformations for structure-based opioid drug design.","whyItMatters":"Relevant for opioid-peptides, peptide-design, receptor-signaling.","specificNumbers":"","methodology":"review study on opioid-peptides, peptide-design.","limitations":"See abstract."},{"rthcId":"RPEP-00954","title":"Correlation of plasma concentrations of B-type natriuretic peptide with infarct size quantified by tomographic thallium-201 myocardial scintigraphy in asymptomatic patients with previous myocardial infarction.","authors":"Nakagawa, Kazuya; Umetani, Ken; Fujioka, Daisuke; Sano, Keita; Nakamura, Takamitsu; Kodama, Yasushi; Kitta, Yoshinobu; Ichigi, Yoshihide; Kawabata, Ken-Ichi; Obata, Jyun-Ei; Takano, Hajime; Inobe, Yoshito; Kugiyama, Kiyotaka","year":2004,"journal":"Circulation journal : official journal of the Japanese Circulation Society, 68(10), 923-7","doi":null,"pmid":"15459465","tags":["natriuretic-peptides","cardiovascular","clinical-trials"],"studyType":"cross-sectional","evidenceStrength":"moderate","keyFinding":"BNP plasma concentrations correlated significantly with infarct size measured by thallium-201 SPECT in MI patients, providing a blood test surrogate for imaging-determined infarction extent.","whyItMatters":"Relevant for natriuretic-peptides, cardiovascular, clinical-trials.","specificNumbers":"","methodology":"cross-sectional study on natriuretic-peptides, cardiovascular.","limitations":"See abstract."},{"rthcId":"RPEP-00955","title":"Diagnosis of heart failure using urinary natriuretic peptides.","authors":"Ng, L L; Geeranavar, S; Jennings, S C; Loke, I; O'Brien, R J","year":2004,"journal":"Clinical science (London, England : 1979), 106(2), 129-33","doi":null,"pmid":"13678415","tags":["natriuretic-peptides","cardiovascular","clinical-trials"],"studyType":"cross-sectional","evidenceStrength":"moderate","keyFinding":"Urinary N-BNP showed the best diagnostic performance for heart failure detection among urinary natriuretic peptides tested (N-ANP, N-BNP, CNP), offering a non-invasive urine-based alternative to blood sampling.","whyItMatters":"Relevant for natriuretic-peptides, cardiovascular, clinical-trials.","specificNumbers":"","methodology":"cross-sectional study on natriuretic-peptides, cardiovascular.","limitations":"See abstract."},{"rthcId":"RPEP-00956","title":"Neuroendocrine testing in community patients with heart disease: plasma N-terminal proatrial natriuretic peptide predicts morbidity and mortality stronger than catecholamines and heart rate variability.","authors":"Nielsen, O W; Rasmussen, V; Christensen, N J; Hansen, J F","year":2004,"journal":"Scandinavian journal of clinical and laboratory investigation, 64(7), 619-28","doi":null,"pmid":"15513318","tags":["natriuretic-peptides","cardiovascular","clinical-trials"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"N-terminal proANP predicted incident CHF in stable community heart disease patients, with elevated levels identifying those who would progress from compensated heart disease to symptomatic heart failure.","whyItMatters":"Relevant for natriuretic-peptides, cardiovascular, clinical-trials.","specificNumbers":"","methodology":"cohort study on natriuretic-peptides, cardiovascular.","limitations":"See abstract."},{"rthcId":"RPEP-00957","title":"Cross-talk of opioid peptide receptor and beta-adrenergic receptor signalling in the heart.","authors":"Pepe, Salvatore; van den Brink, Olivier W V; Lakatta, Edward G; Xiao, Rui-Ping","year":2004,"journal":"Cardiovascular research, 63(3), 414-22","doi":null,"pmid":"15276466","tags":["opioid-peptides","cardiovascular","receptor-signaling"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Cardiac opioid peptide receptors (delta, kappa) and beta-adrenergic receptors share G-protein signaling pathways, creating functional cross-talk that modulates contractility, arrhythmia susceptibility, and ischemic preconditioning cardioprotection.","whyItMatters":"Relevant for opioid-peptides, cardiovascular, receptor-signaling.","specificNumbers":"","methodology":"review study on opioid-peptides, cardiovascular.","limitations":"See abstract."},{"rthcId":"RPEP-00958","title":"Resistance to the orexigenic effect of ghrelin in dietary-induced obesity in mice: reversal upon weight loss.","authors":"Perreault, M; Istrate, N; Wang, L; Nichols, A J; Tozzo, E; Stricker-Krongrad, A","year":2004,"journal":"International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity, 28(7), 879-85","doi":null,"pmid":"15111983","tags":["gut-and-metabolic-peptides","obesity-and-weight-management"],"studyType":"animal-study","evidenceStrength":"low","keyFinding":"Mice made obese through a high-fat diet developed resistance to ghrelin — the hunger hormone stopped working properly. Specifically, obese mice had lower circulating ghrelin levels, lost the normal daily rhythm of ghrelin secretion, and no longer showed the typical ghrelin spike during fasting and refeeding. When given exogenous ghrelin injections, obese mice ate significantly less in response compared to lean mice.\n\nCritically, when the obese mice lost weight, their sensitivity to ghrelin was restored. The authors suggest this means ghrelin inhibition after weight loss could potentially prevent weight regain — because ghrelin sensitivity returns precisely when it would drive overeating.","whyItMatters":"Weight regain after dieting is the central challenge in obesity treatment. This study reveals a key mechanism: obesity blunts ghrelin signaling, but weight loss restores it. That restored ghrelin sensitivity could be one reason people feel ravenously hungry after losing weight — and why they regain it. Understanding this ghrelin rebound has directly influenced the development of anti-obesity strategies and helps explain why GLP-1 drugs that suppress appetite are so effective at maintaining weight loss.","specificNumbers":"C57BL/6J mice · Low-fat vs high-fat diet · Ghrelin levels reduced in obese mice · Diurnal ghrelin rhythm lost · Fasting ghrelin response abolished · Sensitivity restored with weight loss","methodology":"Lean C57BL/6J mice were fed either chow, a low-fat diet, or a high-fat diet to induce obesity. Researchers measured plasma ghrelin levels, tracked daily ghrelin cycling patterns, tested fasting/refeeding ghrelin responses, and measured food intake after exogenous ghrelin administration in lean versus obese mice.","limitations":"Mouse study — ghrelin physiology differs somewhat between mice and humans. No specific ghrelin receptor or downstream signaling analysis was performed. The mechanism behind ghrelin resistance was not fully characterized. Weight loss intervention details are limited in the abstract."},{"rthcId":"RPEP-00959","title":"Selective facilitation of sexual solicitation in the female rat by a melanocortin receptor agonist.","authors":"Pfaus, James G; Shadiack, Annette; Van Soest, Tanya; Tse, Maric; Molinoff, Perry","year":2004,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 101(27), 10201-4","doi":null,"pmid":"15226502","tags":["pt-141","sexual-health","receptor-signaling","clinical-trials"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"PT-141 (melanocortin agonist) selectively increased sexual solicitation (proceptive) behavior in female rats without affecting locomotion or other behaviors — demonstrating specific melanocortin modulation of female sexual desire/motivation.","whyItMatters":"Relevant for pt-141, sexual-health, receptor-signaling, clinical-trials.","specificNumbers":"","methodology":"animal-study study on pt-141, sexual-health.","limitations":"See abstract."},{"rthcId":"RPEP-00960","title":"Thymosin beta4 promotes angiogenesis, wound healing, and hair follicle development.","authors":"Philp, D; Goldstein, A L; Kleinman, H K","year":2004,"journal":"Mechanisms of ageing and development, 125(2), 113-5","doi":null,"pmid":"15037013","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00961","title":"Thymosin beta4 increases hair growth by activation of hair follicle stem cells.","authors":"Philp, Deborah; Nguyen, Mychi; Scheremeta, Brooke; St-Surin, Sharleen; Villa, Ana M; Orgel, Adam; Kleinman, Hynda K; Elkin, Michael","year":2004,"journal":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 18(2), 385-7","doi":null,"pmid":"14657002","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00962","title":"Antigen presentation to celiac lesion-derived T cells of a 33-mer gliadin peptide naturally formed by gastrointestinal digestion.","authors":"Qiao, Shuo-Wang; Bergseng, Elin; Molberg, Øyvind; Xia, Jiang; Fleckenstein, Burkhard; Khosla, Chaitan; Sollid, Ludvig M","year":2004,"journal":"Journal of immunology (Baltimore, Md. : 1950), 173(3), 1757-62","doi":null,"pmid":"15265905","tags":[],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"A 33-amino-acid gliadin peptide (the '33-mer'), naturally produced by gastrointestinal digestion of wheat gluten, is an exceptionally potent T cell stimulator in celiac disease. It contains six overlapping copies of three T cell epitopes and, after modification by tissue transglutaminase (TG2), binds with high affinity to the HLA-DQ2 immune molecule. Remarkably, the 33-mer doesn't need to be further processed inside immune cells — it can be presented to T cells directly, even by chemically fixed (non-living) antigen-presenting cells. It also binds DQ2 optimally at pH 6.3, promoting extracellular binding.","whyItMatters":"This study revealed why one specific peptide fragment from wheat gluten is so toxic to people with celiac disease. The 33-mer is uniquely resistant to digestion, contains multiple T cell epitopes packed into a single fragment, and doesn't need immune cell processing to trigger an attack. Understanding this 'super-antigen' peptide has been central to developing celiac disease therapies, including enzyme supplements designed to break it down and peptide-based tolerance therapies.","specificNumbers":"33 amino acids · 6 overlapping T cell epitopes (3 types) · Optimal DQ2 binding at pH 6.3 · More potent than 12-mer control · No intracellular processing required","methodology":"In vitro immunology study using T cells derived from celiac disease intestinal biopsies. The 33-mer peptide was tested for DQ2 binding affinity, T cell stimulatory potency, and antigen-presenting cell (APC) requirements using live and glutaraldehyde-fixed EBV-transformed B cells and dendritic cells. Binding pH profiles were characterized.","limitations":"In vitro study using celiac patient-derived T cells — does not address in vivo immune dynamics. Only HLA-DQ2-associated celiac disease studied (most but not all celiac patients carry DQ2). The study characterizes the 33-mer's properties but does not test therapeutic interventions."},{"rthcId":"RPEP-00963","title":"Opioid receptors and acetaminophen (paracetamol).","authors":"Raffa, Robert B; Walker, Ellen A; Sterious, Steven N","year":2004,"journal":"European journal of pharmacology, 503(1-3), 209-10","doi":null,"pmid":"15496316","tags":["opioid-peptides","pain","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Acetaminophen's spinal/supraspinal antinociceptive self-synergy was attenuated by opioid receptor antagonists in mice, demonstrating an opioid receptor component to acetaminophen's pain-relieving mechanism.","whyItMatters":"Relevant for opioid-peptides, pain, receptor-signaling.","specificNumbers":"","methodology":"animal-study study on opioid-peptides, pain.","limitations":"See abstract."},{"rthcId":"RPEP-00964","title":"Amylin replacement with pramlintide as an adjunct to insulin therapy improves long-term glycaemic and weight control in Type 1 diabetes mellitus: a 1-year, randomized controlled trial.","authors":"Ratner, R E; Dickey, R; Fineman, M; Maggs, D G; Shen, L; Strobel, S A; Weyer, C; Kolterman, O G","year":2004,"journal":"Diabetic medicine : a journal of the British Diabetic Association, 21(11), 1204-12","doi":null,"pmid":"15498087","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00965","title":"NT-proBNP in heart failure: therapy decisions and monitoring.","authors":"Richards, Mark; Troughton, Richard W","year":2004,"journal":"European journal of heart failure, 6(3), 351-4","doi":null,"pmid":"14987587","tags":["natriuretic-peptides","cardiovascular","clinical-trials"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"NT-proBNP serves as both a diagnostic tool and a treatment monitoring biomarker in heart failure, with serial measurements guiding drug titration and tracking therapeutic response for personalized care.","whyItMatters":"Relevant for natriuretic-peptides, cardiovascular, clinical-trials.","specificNumbers":"","methodology":"review study on natriuretic-peptides, cardiovascular.","limitations":"See abstract."},{"rthcId":"RPEP-00966","title":"Structure-activity studies on the corticotropin releasing factor antagonist astressin, leading to a minimal sequence necessary for antagonistic activity.","authors":"Rijkers, Dirk T S; Kruijtzer, John A W; van Oostenbrugge, Marja; Ronken, Eric; den Hartog, Jack A J; Liskamp, Rob M J","year":2004,"journal":"Chembiochem : a European journal of chemical biology, 5(3), 340-8","doi":null,"pmid":"14997526","tags":["neuropeptides","anxiety-mood","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"SAR studies on astressin identified the minimal CRF antagonist sequence retaining biological activity at both CRF1 and CRF2 receptors, advancing design of smaller, more drug-like peptide antagonists for stress-related psychiatric disorders.","whyItMatters":"Relevant for neuropeptides, anxiety-mood, peptide-design.","specificNumbers":"","methodology":"in-vitro study on neuropeptides, anxiety-mood.","limitations":"See abstract."},{"rthcId":"RPEP-00967","title":"Thymosin alpha 1 activates dendritic cells for antifungal Th1 resistance through toll-like receptor signaling.","authors":"Romani, Luigina; Bistoni, Francesco; Gaziano, Roberta; Bozza, Silvia; Montagnoli, Claudia; Perruccio, Katia; Pitzurra, Lucia; Bellocchio, Silvia; Velardi, Andrea; Rasi, Guido; Di Francesco, Paolo; Garaci, Enrico","year":2004,"journal":"Blood, 103(11), 4232-9","doi":null,"pmid":"14982877","tags":["thymosin-alpha-1","immune-function","infection","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Thymosin alpha-1 activated dendritic cells for Th1 antifungal resistance through toll-like receptor (TLR) signaling pathways, providing a specific innate immune mechanism for its anti-infectious properties and positioning it for fungal infection immunotherapy.","whyItMatters":"Relevant for thymosin-alpha-1, immune-function, infection, receptor-signaling.","specificNumbers":"","methodology":"in-vitro study on thymosin-alpha-1, immune-function.","limitations":"See abstract."},{"rthcId":"RPEP-00968","title":"Relative contribution of endogenous opioids to myocardial ischemic tolerance.","authors":"Romano, Matthew A; Seymour, Elisabeth M; Berry, Jennifer A; McNish, Robert A; Bolling, Steven F","year":2004,"journal":"The Journal of surgical research, 118(1), 32-7","doi":null,"pmid":"15093714","tags":["opioid-peptides","cardiovascular","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Selective opioid receptor and peptide antibody blocking revealed delta-opioid (enkephalin) and kappa-opioid (dynorphin) systems as the primary contributors to myocardial ischemic tolerance, with quantified relative contributions of each endogenous opioid family.","whyItMatters":"Relevant for opioid-peptides, cardiovascular, receptor-signaling.","specificNumbers":"","methodology":"animal-study study on opioid-peptides, cardiovascular.","limitations":"See abstract."},{"rthcId":"RPEP-00969","title":"Evaluation of the safety, pharmacokinetics and pharmacodynamic effects of subcutaneously administered PT-141, a melanocortin receptor agonist, in healthy male subjects and in patients with an inadequate response to Viagra.","authors":"Rosen, R C; Diamond, L E; Earle, D C; Shadiack, A M; Molinoff, P B","year":2004,"journal":"International journal of impotence research, 16(2), 135-42","doi":null,"pmid":"14999221","tags":["pt-141","sexual-health","clinical-trials","bioavailability"],"studyType":"RCT","evidenceStrength":"moderate","keyFinding":"SC PT-141 induced dose-dependent erectile responses in ED patients (double-blind, placebo-controlled) with characterized pharmacokinetics, acceptable safety, and practical SC delivery — advancing toward clinical approval.","whyItMatters":"Relevant for pt-141, sexual-health, clinical-trials, bioavailability.","specificNumbers":"","methodology":"RCT study on pt-141, sexual-health.","limitations":"See abstract."},{"rthcId":"RPEP-00970","title":"Emerging roles of urotensin-II in cardiovascular disease.","authors":"Russell, Fraser D","year":2004,"journal":"Pharmacology & therapeutics, 103(3), 223-43","doi":null,"pmid":"15464591","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00971","title":"Interactions between NPY and CRF in the amygdala to regulate emotionality.","authors":"Sajdyk, Tammy J; Shekhar, Anantha; Gehlert, Donald R","year":2004,"journal":"Neuropeptides, 38(4), 225-34","doi":null,"pmid":"15337374","tags":["neuropeptides","anxiety-mood","addiction","receptor-signaling"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Amygdalar NPY-CRF interactions constitute an anxiety-resilience balance: CRF promotes fear/anxiety through CRF1 while NPY opposes through Y1 receptors — imbalance drives anxiety disorders, PTSD, and addiction.","whyItMatters":"Relevant for neuropeptides, anxiety-mood, addiction, receptor-signaling.","specificNumbers":"","methodology":"review study on neuropeptides, anxiety-mood.","limitations":"See abstract."},{"rthcId":"RPEP-00972","title":"Anti-complement effects of lactoferrin-derived peptides.","authors":"Samuelsen, Ørjan; Haukland, Hanne H; Ulvatne, Hilde; Vorland, Lars H","year":2004,"journal":"FEMS immunology and medical microbiology, 41(2), 141-8","doi":null,"pmid":"15145458","tags":["antimicrobial-peptides","immune-function","inflammation"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Lactoferrin-derived peptides showed anti-complement activity, inhibiting complement cascade activation and adding immune modulation beyond antimicrobial effects to the lactoferricin functional profile.","whyItMatters":"Relevant for antimicrobial-peptides, immune-function, inflammation.","specificNumbers":"","methodology":"in-vitro study on antimicrobial-peptides, immune-function.","limitations":"See abstract."},{"rthcId":"RPEP-00973","title":"Gut peptides and other regulators in obesity.","authors":"Scharf, Matthew T; Ahima, Rexford S","year":2004,"journal":"Seminars in liver disease, 24(4), 335-47","doi":null,"pmid":"15605302","tags":["glp-1","ghrp","weight-loss","gut-healing"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Gut peptide-based obesity drugs including GLP-1 agonists, PYY analogs, oxyntomodulin, and ghrelin antagonists represent the most promising peripheral anti-obesity targets, with GLP-1 showing the most advanced clinical development.","whyItMatters":"Relevant for glp-1, ghrp, weight-loss, gut-healing.","specificNumbers":"","methodology":"review study on glp-1, ghrp.","limitations":"See abstract."},{"rthcId":"RPEP-00974","title":"Biology of eating behavior in obesity.","authors":"Schwartz, Gary J","year":2004,"journal":"Obesity research, 12 Suppl 2, 102S-6S","doi":null,"pmid":"15601957","tags":["glp-1","neuropeptides","weight-loss"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Eating behavior in obesity reflects disrupted multi-level peptide signaling: blunted gut satiety peptides (GLP-1, PYY, CCK), altered opioid reward processing, ghrelin dysregulation, and impaired central neuropeptide circuits — biology driving behavioral excess.","whyItMatters":"Relevant for glp-1, neuropeptides, weight-loss.","specificNumbers":"","methodology":"review study on glp-1, neuropeptides.","limitations":"See abstract."},{"rthcId":"RPEP-00975","title":"The world of beta- and gamma-peptides comprised of homologated proteinogenic amino acids and other components.","authors":"Seebach, Dieter; Beck, Albert K; Bierbaum, Daniel J","year":2004,"journal":"Chemistry & biodiversity, 1(8), 1111-239","doi":null,"pmid":"17191902","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00976","title":"Activation of tumor-associated macrophages by thymosin alpha 1.","authors":"Shrivastava, P; Singh, S M; Singh, N","year":2004,"journal":"International journal of immunopathology and pharmacology, 17(1), 39-47","doi":null,"pmid":"15000865","tags":["thymosin-alpha-1","cancer","immune-function"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Thymosin alpha-1 reprogrammed tumor-associated macrophages from immunosuppressive to tumoricidal phenotype, enabling them to kill cancer cells directly — overcoming a key immune evasion mechanism of the tumor microenvironment.","whyItMatters":"Relevant for thymosin-alpha-1, cancer, immune-function.","specificNumbers":"","methodology":"animal-study study on thymosin-alpha-1, cancer.","limitations":"See abstract."},{"rthcId":"RPEP-00977","title":"Effect of thymosin alpha 1 on the antitumor activity of tumor-associated macrophage-derived dendritic cells.","authors":"Shrivastava, Pratima; Singh, Sukh Mahendra; Singh, Nisha","year":2004,"journal":"Journal of biomedical science, 11(5), 623-30","doi":null,"pmid":"15316138","tags":["thymosin-alpha-1","cancer","immune-function"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Thymosin alpha-1 promoted differentiation of tumor-associated macrophages into functional dendritic cells with enhanced antigen presentation and antitumor activity — converting tumor immune suppressor cells into effective cancer fighters.","whyItMatters":"Relevant for thymosin-alpha-1, cancer, immune-function.","specificNumbers":"","methodology":"animal-study study on thymosin-alpha-1, cancer.","limitations":"See abstract."},{"rthcId":"RPEP-00978","title":"Gut hormones as peripheral anti obesity targets.","authors":"Small, Caroline J; Bloom, Stephen R","year":2004,"journal":"Current drug targets. CNS and neurological disorders, 3(5), 379-88","doi":null,"pmid":"15544446","tags":["glp-1","neuropeptides","weight-loss","clinical-trials"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Peripheral gut hormone-based obesity drug development focuses on GLP-1 agonists (most advanced), PYY analogs, oxyntomodulin, amylin analogs, and PP as practical anti-obesity drug targets with established physiological rationale and clinical precedent.","whyItMatters":"Relevant for glp-1, neuropeptides, weight-loss, clinical-trials.","specificNumbers":"","methodology":"review study on glp-1, neuropeptides.","limitations":"See abstract."},{"rthcId":"RPEP-00979","title":"Growth hormone secretagogues: prospects and potential pitfalls.","authors":"Smith, Roy G; Sun, Yuxiang; Betancourt, Lorena; Asnicar, Mark","year":2004,"journal":"Best practice & research. Clinical endocrinology & metabolism, 18(3), 333-47","doi":null,"pmid":"15261841","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00980","title":"N-terminal pro-atrial natriuretic peptide (N-ANP) and N-terminal pro-B-type natriuretic peptide (N-BNP) in the prediction of death and heart failure in unselected patients following acute myocardial infarction.","authors":"Squire, Iain B; O'Brien, Russell J; Demme, Bettina; Davies, Joan E; Ng, Leong L","year":2004,"journal":"Clinical science (London, England : 1979), 107(3), 309-16","doi":null,"pmid":"15182235","tags":["natriuretic-peptides","cardiovascular","clinical-trials"],"studyType":"cohort","evidenceStrength":"strong","keyFinding":"N-ANP and NT-proBNP both independently predicted cardiovascular events in stable community heart disease patients, with combined measurement providing superior risk stratification for identifying those who would develop CHF or cardiac death.","whyItMatters":"Relevant for natriuretic-peptides, cardiovascular, clinical-trials.","specificNumbers":"","methodology":"cohort study on natriuretic-peptides, cardiovascular.","limitations":"See abstract."},{"rthcId":"RPEP-00981","title":"Identification of an Adrenomedullin precursor fragment in plasma of sepsis patients.","authors":"Struck, Joachim; Tao, Chen; Morgenthaler, Nils G; Bergmann, Andreas","year":2004,"journal":"Peptides, 25(8), 1369-72","doi":null,"pmid":"15350706","tags":["neuropeptides","cardiovascular","clinical-trials"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"A mid-regional pro-adrenomedullin (MR-proADM) fragment was identified and quantified in sepsis patient plasma, providing a stable, measurable surrogate for the unstable mature adrenomedullin — establishing the basis for clinical MR-proADM sepsis testing.","whyItMatters":"Relevant for neuropeptides, cardiovascular, clinical-trials.","specificNumbers":"","methodology":"clinical-trial study on neuropeptides, cardiovascular.","limitations":"See abstract."},{"rthcId":"RPEP-00982","title":"Ghrelin stimulation of growth hormone release and appetite is mediated through the growth hormone secretagogue receptor.","authors":"Sun, Yuxiang; Wang, Pei; Zheng, Hui; Smith, Roy G","year":2004,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 101(13), 4679-84","doi":null,"pmid":"15070777","tags":["ghrp","hormone-optimization","weight-loss","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"strong","keyFinding":"GHS-R knockout mice showed no GH release or appetite stimulation from ghrelin administration, definitively proving both effects require the GHS-R — settling the debate about whether ghrelin uses alternative receptors for appetite.","whyItMatters":"Relevant for ghrp, hormone-optimization, weight-loss, receptor-signaling.","specificNumbers":"","methodology":"animal-study study on ghrp, hormone-optimization.","limitations":"See abstract."},{"rthcId":"RPEP-00983","title":"Natriuretic peptide system: physiology and clinical utility.","authors":"Suttner, Stefan W; Boldt, Joachim","year":2004,"journal":"Current opinion in critical care, 10(5), 336-41","doi":null,"pmid":"15385748","tags":["natriuretic-peptides","cardiovascular"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Natriuretic peptide system physiology (ANP/BNP cardiac production, NPR-A/B/C receptors, clearance mechanisms) directly underlies their clinical utility for heart failure diagnosis, prognosis, population screening, and treatment monitoring.","whyItMatters":"Relevant for natriuretic-peptides, cardiovascular.","specificNumbers":"","methodology":"review study on natriuretic-peptides, cardiovascular.","limitations":"See abstract."},{"rthcId":"RPEP-00984","title":"Short sleep duration is associated with reduced leptin, elevated ghrelin, and increased body mass index.","authors":"Taheri, Shahrad; Lin, Ling; Austin, Diane; Young, Terry; Mignot, Emmanuel","year":2004,"journal":"PLoS medicine, 1(3), e62","doi":null,"pmid":"15602591","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00985","title":"The vasopressin V1b receptor critically regulates hypothalamic-pituitary-adrenal axis activity under both stress and resting conditions.","authors":"Tanoue, Akito; Ito, Shuji; Honda, Kenji; Oshikawa, Sayuri; Kitagawa, Yoko; Koshimizu, Taka-Aki; Mori, Toyoki; Tsujimoto, Gozoh","year":2004,"journal":"The Journal of clinical investigation, 113(2), 302-9","doi":null,"pmid":"14722621","tags":["vasopressin","HPA-axis"],"studyType":"animal-study","evidenceStrength":"strong","keyFinding":"Mice engineered without the vasopressin V1b receptor had significantly lower baseline levels of both ACTH and corticosterone — the key hormones that drive the body's stress response. When stressed (forced swimming), these knockout mice showed a blunted ACTH surge compared to normal mice. The V1b receptor responds to vasopressin but not to CRH (corticotropin-releasing hormone), confirming that vasopressin's stress-axis effects work through a distinct pathway.\n\nCritically, the V1b receptor wasn't just important during stress — it also maintained baseline hormone levels under resting conditions. This means vasopressin isn't just a stress-response amplifier; it's an essential regulator of the entire HPA axis at all times.","whyItMatters":"The HPA axis (hypothalamic-pituitary-adrenal axis) is the body's central stress response system, and its dysregulation is linked to depression, anxiety, PTSD, and metabolic disorders. This study showed that vasopressin — a peptide hormone — is a critical regulator of this system, not just under stress but also at baseline. This opened the door to developing V1b receptor antagonists as potential treatments for stress-related psychiatric disorders.","specificNumbers":"V1bR-/- mice had lower baseline ACTH and corticosterone · AVP-stimulated ACTH release impaired · CRH-stimulated ACTH release unaffected · forced swim stress ACTH response suppressed","methodology":"Gene targeting to create knockout mice lacking the V1b receptor gene (V1bR-/-). Compared ACTH and corticosterone levels between knockout and wild-type mice at rest and under stress (forced swim test). Also tested vasopressin- and CRH-stimulated ACTH release from cultured pituitary cells.","limitations":"Mouse model — findings may not directly translate to human HPA axis regulation. The knockout completely removes V1b receptor function rather than partially blocking it, which is more extreme than what a drug would do. Behavioral and cognitive effects of altered HPA axis function were not assessed."},{"rthcId":"RPEP-00986","title":"Effect of Helicobacter pylori infection on ghrelin expression in human gastric mucosa.","authors":"Tatsuguchi, Atsushi; Miyake, Kazumasa; Gudis, Katya; Futagami, Seiji; Tsukui, Taku; Wada, Ken; Kishida, Teruyuki; Fukuda, Yuh; Sugisaki, Yuichi; Sakamoto, Choitsu","year":2004,"journal":"The American journal of gastroenterology, 99(11), 2121-7","doi":null,"pmid":"15554990","tags":["ghrp","gut-healing","infection","hormone-optimization"],"studyType":"cross-sectional","evidenceStrength":"moderate","keyFinding":"H. pylori infection significantly altered gastric ghrelin mRNA and protein expression, with changes correlating with infection severity and potentially explaining H. pylori-associated appetite changes and the weight gain often seen after eradication treatment.","whyItMatters":"Relevant for ghrp, gut-healing, infection, hormone-optimization.","specificNumbers":"","methodology":"cross-sectional study on ghrp, gut-healing.","limitations":"See abstract."},{"rthcId":"RPEP-00987","title":"Effects of pentadecapeptide BPC157 on regional serotonin synthesis in the rat brain: alpha-methyl-L-tryptophan autoradiographic measurements.","authors":"Tohyama, Y; Sikirić, P; Diksic, M","year":2004,"journal":"Life sciences, 76(3), 345-57","doi":null,"pmid":"15531385","tags":["bpc-157","anxiety-mood","neuroprotection","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"BPC-157 produced region-specific changes in brain serotonin synthesis measured by alpha-methyl-L-tryptophan autoradiography — increasing synthesis in some regions while decreasing it in others, providing the serotonergic basis for its mood-modulating properties.","whyItMatters":"Relevant for bpc-157, anxiety-mood, neuroprotection, receptor-signaling.","specificNumbers":"","methodology":"animal-study study on bpc-157, anxiety-mood.","limitations":"See abstract."},{"rthcId":"RPEP-00988","title":"Lactoferricin B inhibits bacterial macromolecular synthesis in Escherichia coli and Bacillus subtilis.","authors":"Ulvatne, Hilde; Samuelsen, Ørjan; Haukland, Hanne H; Krämer, Manuela; Vorland, Lars H","year":2004,"journal":"FEMS microbiology letters, 237(2), 377-84","doi":null,"pmid":"15321686","tags":["antimicrobial-peptides","infection"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Lactoferricin B inhibited DNA, RNA, and protein synthesis in E. coli and B. subtilis at sub-MIC concentrations, demonstrating an intracellular mechanism of antimicrobial action complementing its known membrane-disrupting activity.","whyItMatters":"Relevant for antimicrobial-peptides, infection.","specificNumbers":"","methodology":"in-vitro study on antimicrobial-peptides, infection.","limitations":"See abstract."},{"rthcId":"RPEP-00989","title":"Lactoferrampin: a novel antimicrobial peptide in the N1-domain of bovine lactoferrin.","authors":"van der Kraan, Marieke I A; Groenink, Jasper; Nazmi, Kamran; Veerman, Enno C I; Bolscher, Jan G M; Nieuw Amerongen, Arie V","year":2004,"journal":"Peptides, 25(2), 177-83","doi":null,"pmid":"15062998","tags":["antimicrobial-peptides","infection","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Lactoferrampin, a novel antimicrobial peptide from the N1-domain of bovine lactoferrin (distinct from lactoferricin in the N-lobe), showed broad antimicrobial activity — expanding the number of bioactive peptides derived from this single milk protein.","whyItMatters":"Relevant for antimicrobial-peptides, infection, peptide-design.","specificNumbers":"","methodology":"in-vitro study on antimicrobial-peptides, infection.","limitations":"See abstract."},{"rthcId":"RPEP-00990","title":"Age and secretagogue type jointly determine dynamic growth hormone responses to exogenous insulin-like growth factor-negative feedback in healthy men.","authors":"Veldhuis, Johannes D; Weltman, Judith Y; Weltman, Arthur L; Iranmanesh, Ali; Muller, Eugenio E; Bowers, Cyril Y","year":2004,"journal":"The Journal of clinical endocrinology and metabolism, 89(11), 5542-8","doi":null,"pmid":"15531509","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00991","title":"Contrasting negative-feedback control of endogenously driven and exercise-stimulated pulsatile growth hormone secretion in women and men.","authors":"Veldhuis, Johannes D; Patrie, James; Wideman, Laurie; Patterson, Mark; Weltman, Judy Y; Weltman, Arthur","year":2004,"journal":"The Journal of clinical endocrinology and metabolism, 89(2), 840-6","doi":null,"pmid":"14764803","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00992","title":"Activation of apoptosis in vivo by a hydrocarbon-stapled BH3 helix.","authors":"Walensky, Loren D; Kung, Andrew L; Escher, Iris; Malia, Thomas J; Barbuto, Scott; Wright, Renee D; Wagner, Gerhard; Verdine, Gregory L; Korsmeyer, Stanley J","year":2004,"journal":"Science (New York, N.Y.), 305(5689), 1466-70","doi":null,"pmid":"15353804","tags":["cyclic-peptides","cancer","peptide-design"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"A hydrocarbon-stapled BH3 alpha-helix peptide activated apoptosis in vivo in a mouse leukemia model, producing tumor reduction — the first demonstration that stapled peptide technology achieves in-vivo anticancer efficacy through intracellular target engagement.","whyItMatters":"Relevant for cyclic-peptides, cancer, peptide-design.","specificNumbers":"","methodology":"animal-study study on cyclic-peptides, cancer.","limitations":"See abstract."},{"rthcId":"RPEP-00993","title":"AOD-9604 Metabolic.","authors":"Wilding, John","year":2004,"journal":"Current opinion in investigational drugs (London, England : 2000), 5(4), 436-40","doi":null,"pmid":"15134286","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00994","title":"Non-opioid actions of opioid peptides.","authors":"Wollemann, Mária; Benyhe, Sándor","year":2004,"journal":"Life sciences, 75(3), 257-70","doi":null,"pmid":"15135648","tags":["opioid-peptides","immune-function","receptor-signaling","neuroprotection"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Endogenous opioid peptides have extensive non-opioid receptor activities: immune modulation, cell proliferation control (via OGFr), cardiovascular protection, neuroprotection, and antimicrobial effects — mediated through non-classical receptors and direct physicochemical mechanisms.","whyItMatters":"Relevant for opioid-peptides, immune-function, receptor-signaling, neuroprotection.","specificNumbers":"","methodology":"review study on opioid-peptides, immune-function.","limitations":"See abstract."},{"rthcId":"RPEP-00995","title":"Amino-terminal pro-C-type natriuretic peptide in heart failure.","authors":"Wright, Sue P; Prickett, Tim C R; Doughty, Robert N; Frampton, Chris; Gamble, Greg D; Yandle, Tim G; Sharpe, Norman; Richards, Mark","year":2004,"journal":"Hypertension (Dallas, Tex. : 1979), 43(1), 94-100","doi":null,"pmid":"14656955","tags":["natriuretic-peptides","cardiovascular","clinical-trials"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"NT-proCNP (endothelial origin, unlike cardiac ANP/BNP) was elevated in heart failure and correlated with severity, providing a biomarker reflecting vascular endothelial dysfunction to complement cardiac-derived natriuretic peptides.","whyItMatters":"Relevant for natriuretic-peptides, cardiovascular, clinical-trials.","specificNumbers":"","methodology":"cohort study on natriuretic-peptides, cardiovascular.","limitations":"See abstract."},{"rthcId":"RPEP-00996","title":"Nonopioidergic mechanism mediating morphine-induced antianalgesia in the mouse spinal cord.","authors":"Wu, Hsiang-En; Thompson, Jonathan; Sun, Han-Sen; Leitermann, Randy J; Fujimoto, James M; Tseng, Leon F","year":2004,"journal":"The Journal of pharmacology and experimental therapeutics, 310(1), 240-6","doi":null,"pmid":"14999057","tags":["opioid-peptides","pain","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"High-dose IT morphine produced anti-analgesia mediated by spinal dynorphin release and NMDA receptor activation (blocked by MK-801 and anti-dynorphin), demonstrating a universal opioid-induced hyperalgesia mechanism across both synthetic and endogenous opioids.","whyItMatters":"Relevant for opioid-peptides, pain, receptor-signaling.","specificNumbers":"","methodology":"animal-study study on opioid-peptides, pain.","limitations":"See abstract."},{"rthcId":"RPEP-00997","title":"The gut and regulation of body weight.","authors":"Wynne, Katie; Stanley, Sarah; Bloom, Steve","year":2004,"journal":"The Journal of clinical endocrinology and metabolism, 89(6), 2576-82","doi":null,"pmid":"15181026","tags":["glp-1","ghrp","weight-loss","gut-healing"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Gut hormones (GLP-1, PYY, ghrelin, CCK, oxyntomodulin) regulate body weight through coordinated appetite and energy expenditure signaling, with GLP-1 receptor agonists showing the most advanced clinical development for obesity treatment.","whyItMatters":"Relevant for glp-1, ghrp, weight-loss, gut-healing.","specificNumbers":"","methodology":"review study on glp-1, ghrp.","limitations":"See abstract."},{"rthcId":"RPEP-00998","title":"Neuropeptide S: a neuropeptide promoting arousal and anxiolytic-like effects.","authors":"Xu, Yan-Ling; Reinscheid, Rainer K; Huitron-Resendiz, Salvador; Clark, Stewart D; Wang, Zhiwei; Lin, Steven H; Brucher, Fernando A; Zeng, Joanne; Ly, Nga K; Henriksen, Steven J; de Lecea, Luis; Civelli, Olivier","year":2004,"journal":"Neuron, 43(4), 487-97","doi":null,"pmid":"15312648","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-00999","title":"Protective effects of pentadecapeptide BPC 157 on gastric ulcer in rats.","authors":"Xue, Xiao-Chang; Wu, Yong-Jie; Gao, Ming-Tang; Li, Wen-Guang; Zhao, Ning; Wang, Zeng-Lu; Bao, Chun-Jie; Yan, Zhen; Zhang, Ying-Qi","year":2004,"journal":"World journal of gastroenterology, 10(7), 1032-6","doi":null,"pmid":"15052688","tags":["bpc-157","gut-healing"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"BPC-157 healed gastric ulcers in multiple rat models through comprehensive mechanisms: promoted angiogenesis, reduced inflammation, enhanced cytoprotection, and accelerated mucosal regeneration — acting through pathways independent of acid secretion reduction.","whyItMatters":"Relevant for bpc-157, gut-healing.","specificNumbers":"","methodology":"animal-study study on bpc-157, gut-healing.","limitations":"See abstract."},{"rthcId":"RPEP-01000","title":"Identification of membrane-anchoring domains of RLIP76 using deletion mutant analyses.","authors":"Yadav, Sushma; Singhal, Sharad S; Singhal, Jyotsana; Wickramarachchi, Dilki; Knutson, Eugene; Albrecht, Thomas B; Awasthi, Yogesh C; Awasthi, Sanjay","year":2004,"journal":"Biochemistry, 43(51), 16243-53","doi":null,"pmid":"15610018","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01001","title":"Effect of GHRH and GHRP-2 treatment in vitro on GH secretion and levels of GH, pituitary transcription factor-1, GHRH-receptor, GH-secretagogue-receptor and somatostatin receptor mRNAs in ovine pituitary cells.","authors":"Yan, Ming; Hernandez, Maria; Xu, Ruwei; Chen, Chen","year":2004,"journal":"European journal of endocrinology, 150(2), 235-42","doi":null,"pmid":"14763922","tags":["ghrp","cjc-1295","hormone-optimization","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"In-vitro GHRP-2 treatment altered pituitary somatotroph expression of GH, Pit-1 transcription factor, GHRH-R, and GHS-R at mRNA and protein levels, demonstrating GH secretagogue-induced pituitary cell reprogramming for enhanced GH-axis responsiveness.","whyItMatters":"Relevant for ghrp, cjc-1295, hormone-optimization, receptor-signaling.","specificNumbers":"","methodology":"in-vitro study on ghrp, cjc-1295.","limitations":"See abstract."},{"rthcId":"RPEP-01002","title":"Natriuretic peptides, respiratory disease, and the right heart.","authors":"Yap, Lok Bin; Mukerjee, Dev; Timms, Peter M; Ashrafian, Houman; Coghlan, John Gerard","year":2004,"journal":"Chest, 126(4), 1330-6","doi":null,"pmid":"15486400","tags":["natriuretic-peptides","cardiovascular","respiratory"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Natriuretic peptides (BNP, NT-proBNP) are clinically useful for distinguishing cardiac from respiratory causes of dyspnea, diagnosing pulmonary hypertension, and monitoring right ventricular function in patients with chronic respiratory disease.","whyItMatters":"Relevant for natriuretic-peptides, cardiovascular, respiratory.","specificNumbers":"","methodology":"review study on natriuretic-peptides, cardiovascular.","limitations":"See abstract."},{"rthcId":"RPEP-01003","title":"Molecular dynamics simulations of bovine lactoferricin: turning a helix into a sheet.","authors":"Zhou, Ning; Tieleman, D Peter; Vogel, Hans J","year":2004,"journal":"Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine, 17(3), 217-23","doi":null,"pmid":"15222468","tags":["antimicrobial-peptides","peptide-design","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"MD simulations showed bovine lactoferricin transforms from alpha-helix to beta-sheet at membrane surfaces, with the sheet conformation enabling deep membrane penetration — revealing the dynamic structural basis for its antimicrobial membrane disruption.","whyItMatters":"Relevant for antimicrobial-peptides, peptide-design, receptor-signaling.","specificNumbers":"","methodology":"in-vitro study on antimicrobial-peptides, peptide-design.","limitations":"See abstract."},{"rthcId":"RPEP-01004","title":"Effects of long-term treatment with growth hormone-releasing peptide-2 in the GHRH knockout mouse.","authors":"Alba, Maria; Fintini, Danilo; Bowers, Cyril Y; Parlow, A F; Salvatori, Roberto","year":2005,"journal":"American journal of physiology. Endocrinology and metabolism, 289(5), E762-7","doi":null,"pmid":"15985453","tags":["ghrp","hormone-optimization","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Long-term GHRP-2 treatment in GHRH knockout mice maintained GH secretion and body composition effects, demonstrating that GH secretagogues can sustainably stimulate GH through GHRH-independent pathways — important for conditions with GHRH deficiency.","whyItMatters":"Relevant for ghrp, hormone-optimization, receptor-signaling.","specificNumbers":"","methodology":"animal-study study on ghrp, hormone-optimization.","limitations":"See abstract."},{"rthcId":"RPEP-01005","title":"Peptide-based immunotherapy: a novel strategy for allergic disease.","authors":"Ali, F Runa; Larché, Mark","year":2005,"journal":"Expert review of vaccines, 4(6), 881-9","doi":null,"pmid":"16372883","tags":["peptide-vaccines"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Short synthetic peptides derived from allergens — corresponding to T-cell epitopes — can induce immune tolerance without triggering the dangerous IgE-mediated allergic reactions that plague traditional whole-allergen immunotherapy ('allergy shots'). Because these peptide fragments are too small to cross-link the IgE antibodies on mast cells and basophils, they avoid triggering systemic allergic reactions while still teaching the immune system to tolerate the allergen.\n\nRecent clinical trial data indicates that these peptide vaccines work by inducing or expanding a population of antigen-specific regulatory T-cells, which actively suppress the allergic immune response. The same epitope-specific approach also shows promise for treating autoimmune diseases.","whyItMatters":"Traditional allergy immunotherapy carries real risks of severe allergic reactions because it uses whole allergen proteins. Peptide-based vaccines represent a fundamentally safer approach — they target only the T-cell arm of the immune response while avoiding the IgE-mediated arm that causes anaphylaxis. This could make immunotherapy accessible to patients who currently cannot tolerate conventional allergy shots.","specificNumbers":"Not specified in abstract (review article summarizing clinical trial data)","methodology":"This is an expert review article summarizing clinical trial evidence and mechanistic research on peptide-based immunotherapy for allergic diseases. It evaluates data from trials using short synthetic allergen-derived peptides as therapeutic vaccines and discusses the immunological mechanisms of tolerance induction.","limitations":"As a review article, this does not present new original data. The precise mechanism of tolerance induction was noted as incompletely defined at the time of publication. The review does not provide specific efficacy numbers from clinical trials or detail long-term outcomes."},{"rthcId":"RPEP-01006","title":"Enhancement of endotoxin neutralization by coupling of a C12-alkyl chain to a lactoferricin-derived peptide.","authors":"Andrä, Jörg; Lohner, Karl; Blondelle, Sylvie E; Jerala, Roman; Moriyon, Ignacio; Koch, Michel H J; Garidel, Patrick; Brandenburg, Klaus","year":2005,"journal":"The Biochemical journal, 385(Pt 1), 135-43","doi":null,"pmid":"15344905","tags":["antimicrobial-peptides","infection","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"C12-alkyl chain coupling to a lactoferricin-derived peptide enhanced LPS neutralization by over 10-fold while maintaining antimicrobial activity, creating a dual-function peptide that both kills bacteria and neutralizes their toxic products.","whyItMatters":"Relevant for antimicrobial-peptides, infection, peptide-design.","specificNumbers":"","methodology":"in-vitro study on antimicrobial-peptides, infection.","limitations":"See abstract."},{"rthcId":"RPEP-01007","title":"Biotinylated GHK peptide incorporated collagenous matrix: A novel biomaterial for dermal wound healing in rats.","authors":"Arul, V; Gopinath, D; Gomathi, K; Jayakumar, R","year":2005,"journal":"Journal of biomedical materials research. Part B, Applied biomaterials, 73(2), 383-91","doi":null,"pmid":"15803494","tags":["ghk-cu","wound-healing","skin-repair","peptide-delivery"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"GHK peptide incorporated into a biotinylated collagenous wound dressing accelerated rat dermal wound healing: faster wound closure, enhanced granulation tissue formation, improved collagen deposition, and better overall histological healing scores versus scaffold alone.","whyItMatters":"Relevant for ghk-cu, wound-healing, skin-repair, peptide-delivery.","specificNumbers":"","methodology":"animal-study study on ghk-cu, wound-healing.","limitations":"See abstract."},{"rthcId":"RPEP-01008","title":"The endogenous peptide apelin potently improves cardiac contractility and reduces cardiac loading in vivo.","authors":"Ashley, Euan A; Powers, Jennifer; Chen, Mary; Kundu, Ramendra; Finsterbach, Tom; Caffarelli, Anthony; Deng, Alicia; Eichhorn, Jens; Mahajan, Raina; Agrawal, Rani; Greve, Joan; Robbins, Robert; Patterson, Andrew J; Bernstein, Daniel; Quertermous, Thomas","year":2005,"journal":"Cardiovascular research, 65(1), 73-82","doi":null,"pmid":"15621035","tags":[],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"The endogenous peptide apelin powerfully improved heart function in mice without causing harmful heart enlargement. Acute injection increased ventricular elastance by 76% (from 3.7 to 6.5 mmHg/RVU, P=0.018) and nearly doubled preload recruitable stroke work (from 27.4 to 51.8, P=0.059). It also reduced left ventricular end diastolic area (P=0.006) and modestly increased heart rate (P=0.03).\n\nChronic 14-day infusion increased cardiac output by 76% (from 0.142 to 0.25 L/min, P=0.001) and circumferential shortening velocity (P=0.049). Critically, post-mortem analysis showed no cardiac hypertrophy — heart weights and cell sizes were identical between apelin and control groups. The apelin receptor (APJ) was found throughout the adult mouse heart and was expressed in embryonic myocardium as early as day 13.5.","whyItMatters":"Heart failure is a leading cause of death, and most drugs that strengthen the heart's pumping (positive inotropes) eventually cause harmful heart enlargement or increase the risk of dangerous heart rhythms. Apelin achieved the rare combination of improving contractility and reducing cardiac workload without any hypertrophy — exactly the hemodynamic profile clinicians want for heart failure therapy. This positions apelin as a fundamentally different kind of heart-strengthening agent.","specificNumbers":"Acute: 300 μg/kg IP · LVEDA decreased (0.122→0.104 cm², P=0.006) · HR increased (537→559 bpm, P=0.03) · Ventricular elastance +76% (P=0.018) · PRSW +89% (P=0.059) · Chronic: 2 mg/kg/day for 14 days · Cardiac output +76% (P=0.001) · VCF increased (P=0.049) · No hypertrophy (P=0.5 heart weight, P=0.9 cell density)","methodology":"Researchers used three complementary cardiac imaging techniques in C57BL/6 mice: ECG/respiration-gated MRI, conductance catheter pressure-volume measurements, and 15 MHz echocardiography. Acute effects were measured after single IP injection (300 μg/kg). Chronic effects were assessed after 14 days of continuous infusion (2 mg/kg/day via implanted pump). Post-mortem histology and immunohistochemistry evaluated hypertrophy and receptor localization.","limitations":"This is a mouse study in healthy animals, not in heart failure models. The beneficial hemodynamic profile may differ in diseased hearts. Sample sizes appear small (standard deviations suggest small groups), and some P-values approach but don't reach significance (PRSW P=0.059). The 14-day chronic study is relatively short for assessing long-term cardiac remodeling."},{"rthcId":"RPEP-01009","title":"Neurohormonal risk stratification for sudden death and death owing to progressive heart failure in chronic heart failure.","authors":"Berger, R; Huelsmann, M; Strecker, K; Moertl, D; Moser, P; Bojic, A; Pacher, R","year":2005,"journal":"European journal of clinical investigation, 35(1), 24-31","doi":null,"pmid":"15638816","tags":["natriuretic-peptides","cardiovascular","clinical-trials"],"studyType":"cohort","evidenceStrength":"strong","keyFinding":"NT-proBNP was the strongest predictor of progressive heart failure death, while endothelin-1 and norepinephrine better predicted sudden cardiac death — different neurohormones predict different death modes, enabling targeted prevention strategies (ICD vs medical intensification).","whyItMatters":"Relevant for natriuretic-peptides, cardiovascular, clinical-trials.","specificNumbers":"","methodology":"cohort study on natriuretic-peptides, cardiovascular.","limitations":"See abstract."},{"rthcId":"RPEP-01010","title":"The stable gastric pentadecapeptide BPC 157, given locally, improves CO2 laser healing in mice.","authors":"Bilic, M; Bumber, Z; Blagaic, A Boban; Batelja, L; Seiwerth, S; Sikiric, P","year":2005,"journal":"Burns : journal of the International Society for Burn Injuries, 31(3), 310-5","doi":null,"pmid":"15774286","tags":["bpc-157","wound-healing","skin-repair"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Local BPC-157 application accelerated CO2 laser wound healing in mice with faster re-epithelialization and wound contraction, extending BPC-157's documented wound healing to laser-induced tissue damage relevant to surgical and cosmetic dermatology.","whyItMatters":"Relevant for bpc-157, wound-healing, skin-repair.","specificNumbers":"","methodology":"animal-study study on bpc-157, wound-healing.","limitations":"See abstract."},{"rthcId":"RPEP-01011","title":"Gut feeling--the secret of satiety?","authors":"Bloom, Steve; Wynne, Katie; Chaudhri, Owais","year":2005,"journal":"Clinical medicine (London, England), 5(2), 147-52","doi":null,"pmid":"15847007","tags":["glp-1","neuropeptides","weight-loss"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Post-prandial gut hormones (GLP-1, PYY, CCK, oxyntomodulin) signal satiety through vagal and bloodstream pathways to brainstem/hypothalamic circuits, with combination peptide mimicry showing greater satiety than single agents — the future of appetite pharmacology.","whyItMatters":"Relevant for glp-1, neuropeptides, weight-loss.","specificNumbers":"","methodology":"review study on glp-1, neuropeptides.","limitations":"See abstract."},{"rthcId":"RPEP-01012","title":"Gastric pentadecapeptide BPC 157 effective against serotonin syndrome in rats.","authors":"Boban Blagaic, Alenka; Blagaic, Vladimir; Mirt, Mirela; Jelovac, Nikola; Dodig, Goran; Rucman, Rudolf; Petek, Marijan; Turkovic, Branko; Anic, Tomislav; Dubovecak, Miroslav; Staresinic, Mario; Seiwerth, Sven; Sikiric, Predrag","year":2005,"journal":"European journal of pharmacology, 512(2-3), 173-9","doi":null,"pmid":"15840402","tags":["bpc-157","anxiety-mood","neuroprotection"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"BPC-157 effectively counteracted serotonin syndrome signs (hyperthermia, tremor, rigidity, agitation) induced by multiple serotonergic drugs in rats, demonstrating serotonergic system modulation complementing its known dopaminergic and GABAergic interactions.","whyItMatters":"Relevant for bpc-157, anxiety-mood, neuroprotection.","specificNumbers":"","methodology":"animal-study study on bpc-157, anxiety-mood.","limitations":"See abstract."},{"rthcId":"RPEP-01013","title":"The enhancement of osteoblast growth and differentiation in vitro on a peptide hydrogel-polyHIPE polymer hybrid material.","authors":"Bokhari, Maria A; Akay, Galip; Zhang, Shuguang; Birch, Mark A","year":2005,"journal":"Biomaterials, 26(25), 5198-208","doi":null,"pmid":"15792547","tags":["peptide-design","bone-joint"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Osteoblasts cultured on self-assembling peptide hydrogel-polyHIPE polymer hybrid scaffolds demonstrated enhanced proliferation, differentiation, and mineralization compared to control materials, validating peptide-based biomaterials for bone tissue engineering.","whyItMatters":"Relevant for peptide-design, bone-joint.","specificNumbers":"","methodology":"in-vitro study on peptide-design, bone-joint.","limitations":"See abstract."},{"rthcId":"RPEP-01014","title":"Role for hypocretin in mediating stress-induced reinstatement of cocaine-seeking behavior.","authors":"Boutrel, Benjamin; Kenny, Paul J; Specio, Sheila E; Martin-Fardon, Rémi; Markou, Athina; Koob, George F; de Lecea, Luis","year":2005,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 102(52), 19168-73","doi":null,"pmid":"16357203","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01015","title":"Evaluation of interactions between CCK and GLP-1 in their effects on appetite, energy intake, and antropyloroduodenal motility in healthy men.","authors":"Brennan, Ixchel M; Feltrin, Kate L; Horowitz, Michael; Smout, Andre J P M; Meyer, James H; Wishart, Judith; Feinle-Bisset, Christine","year":2005,"journal":"American journal of physiology. Regulatory, integrative and comparative physiology, 288(6), R1477-85","doi":null,"pmid":"15695321","tags":["glp-1","neuropeptides","weight-loss","gut-healing","clinical-trials"],"studyType":"RCT","evidenceStrength":"moderate","keyFinding":"Combined CCK and GLP-1 infusion produced additive effects on appetite suppression and antropyloroduodenal motility in healthy humans — supporting combination gut peptide therapy for superior satiety and weight management.","whyItMatters":"Relevant for glp-1, neuropeptides, weight-loss, gut-healing, clinical-trials.","specificNumbers":"","methodology":"RCT study on glp-1, neuropeptides.","limitations":"See abstract."},{"rthcId":"RPEP-01016","title":"Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria?","authors":"Brogden, Kim A","year":2005,"journal":"Nature reviews. Microbiology, 3(3), 238-50","doi":null,"pmid":"15703760","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Antimicrobial peptides kill bacteria through more mechanisms than just punching holes in membranes. While three classic pore-forming models exist — 'barrel-stave,' 'carpet,' and 'toroidal-pore' — growing evidence shows that many peptides can also cross into bacterial cells and inhibit internal processes including cell wall synthesis, nucleic acid synthesis, protein synthesis, enzymatic activity, and membrane septum formation during cell division.","whyItMatters":"Understanding how antimicrobial peptides actually kill bacteria is essential for developing them as antibiotics. If peptides work through multiple mechanisms simultaneously — membrane disruption and internal target inhibition — bacteria would have a much harder time developing resistance, making these peptides particularly valuable in the age of antibiotic resistance.","specificNumbers":"","methodology":"This is a comprehensive review published in Nature Reviews Microbiology examining the different models of how antimicrobial peptides form pores in bacterial membranes and how they kill microorganisms through intracellular mechanisms. The author synthesized evidence from structural, biophysical, and microbiological studies across invertebrate, plant, and animal species.","limitations":"As a review article, no new experimental data was generated. Many of the pore-forming models were derived from artificial membrane systems that may not perfectly replicate living bacterial membranes. The relative importance of membrane disruption versus intracellular inhibition for any given peptide was not yet fully resolved at the time of publication."},{"rthcId":"RPEP-01017","title":"The role of corticotropin-releasing factor-like peptides in cannabis, nicotine, and alcohol dependence.","authors":"Bruijnzeel, Adrie W; Gold, Mark S","year":2005,"journal":"Brain research. Brain research reviews, 49(3), 505-28","doi":null,"pmid":"16269317","tags":["neuropeptides","addiction","anxiety-mood"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"CRF/urocortin system activation drives the stress/withdrawal component of cannabis, nicotine, and alcohol dependence through CRF1-mediated anxiety during abstinence, creating a negative reinforcement cycle that maintains substance use.","whyItMatters":"Relevant for neuropeptides, addiction, anxiety-mood.","specificNumbers":"","methodology":"review study on neuropeptides, addiction.","limitations":"See abstract."},{"rthcId":"RPEP-01018","title":"Growth hormone-releasing peptide hexarelin reduces neonatal brain injury and alters Akt/glycogen synthase kinase-3beta phosphorylation.","authors":"Brywe, Katarina G; Leverin, Anna-Lena; Gustavsson, Malin; Mallard, Carina; Granata, Riccarda; Destefanis, Silvia; Volante, Marco; Hagberg, Henrik; Ghigo, Ezio; Isgaard, Jörgen","year":2005,"journal":"Endocrinology, 146(11), 4665-72","doi":null,"pmid":"16081643","tags":["ghrp","neuroprotection","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Hexarelin reduced neonatal brain injury in a hypoxia-ischemia model and altered Akt/GSK-3β phosphorylation — activating pro-survival signaling cascades for direct GH-independent neuroprotection in the developing brain.","whyItMatters":"Relevant for ghrp, neuroprotection, receptor-signaling.","specificNumbers":"","methodology":"animal-study study on ghrp, neuroprotection.","limitations":"See abstract."},{"rthcId":"RPEP-01019","title":"Morphine-induced changes in the activity of proopiomelanocortin and prodynorphin systems in zymosan-induced peritonitis in mice.","authors":"Chadzinska, M; Starowicz, K; Scislowska-Czarnecka, A; Bilecki, W; Pierzchala-Koziec, K; Przewlocki, R; Przewlocka, B; Plytycz, B","year":2005,"journal":"Immunology letters, 101(2), 185-92","doi":null,"pmid":"15979727","tags":["opioid-peptides","inflammation","immune-function"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Morphine modified proopiomelanocortin and prodynorphin system activity in immune cells during zymosan-induced peritonitis, demonstrating that exogenous opioid drugs alter the endogenous opioid-immune pain control system at inflammation sites.","whyItMatters":"Relevant for opioid-peptides, inflammation, immune-function.","specificNumbers":"","methodology":"animal-study study on opioid-peptides, inflammation.","limitations":"See abstract."},{"rthcId":"RPEP-01020","title":"Construction and application of a yeast expression system for thymosin alpha1.","authors":"Chen, Feng; Chen, Xiang-Ming; Chen, Zhi; Jiang, Han-Liang; Pan, Xiao-Ping; Hu, Zhong-Rong; Liu, Rong-Hua; Chen, Xiao-Ming","year":2005,"journal":"Biocell : official journal of the Sociedades Latinoamericanas de Microscopia Electronica ... et. al, 29(3), 253-9","doi":null,"pmid":"16524246","tags":["thymosin-alpha-1","peptide-design","bioavailability"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Recombinant thymosin alpha-1 produced in Pichia pastoris yeast expression system showed biological activity equivalent to chemically synthesized peptide, establishing a cost-effective, scalable manufacturing platform for clinical-grade thymosin alpha-1.","whyItMatters":"Relevant for thymosin-alpha-1, peptide-design, bioavailability.","specificNumbers":"","methodology":"in-vitro study on thymosin-alpha-1, peptide-design.","limitations":"See abstract."},{"rthcId":"RPEP-01021","title":"Immunomodulatory function of orally administered thymosin alpha1.","authors":"Chen, Xiang-Ming; Jiang, Han-Liang; Zhou, Lin-Fu; Pan, Xiao-Ping; Hu, Zhong-Rong; Liu, Rong-Hua; Chen, Xiao-Ming; Chen, Zhi","year":2005,"journal":"Journal of Zhejiang University. Science. B, 6(9), 873-6","doi":null,"pmid":"16130188","tags":["thymosin-alpha-1","immune-function","bioavailability","oral-peptides"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Oral thymosin alpha-1 enhanced T-cell function, NK cell activity, and cytokine production in mice, demonstrating that the peptide retains immunomodulatory activity after oral administration — a practical advance for non-injectable immune therapy.","whyItMatters":"Relevant for thymosin-alpha-1, immune-function, bioavailability, oral-peptides.","specificNumbers":"","methodology":"animal-study study on thymosin-alpha-1, immune-function.","limitations":"See abstract."},{"rthcId":"RPEP-01022","title":"GH-releasing peptides and bone.","authors":"Cocchi, D; Maccarinelli, G; Sibilia, V; Tulipano, G; Torsello, A; Pazzaglia, U E; Giustina, A; Netti, C","year":2005,"journal":"Journal of endocrinological investigation, 28(8 Suppl), 11-4","doi":null,"pmid":"16323823","tags":["ghrp","bone-joint","hormone-optimization","receptor-signaling"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"GH-releasing peptides affect bone metabolism through both indirect GH/IGF-1 stimulation and direct ghrelin receptor activation on osteoblasts, promoting bone formation through dual systemic and local mechanisms for potential osteoporosis therapy.","whyItMatters":"Relevant for ghrp, bone-joint, hormone-optimization, receptor-signaling.","specificNumbers":"","methodology":"review study on ghrp, bone-joint.","limitations":"See abstract."},{"rthcId":"RPEP-01023","title":"Solvent and mutation effects on the nucleation of amyloid beta-protein folding.","authors":"Cruz, Luis; Urbanc, Brigita; Borreguero, Jose M; Lazo, Noel D; Teplow, David B; Stanley, H Eugene","year":2005,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 102(51), 18258-63","doi":null,"pmid":"16339896","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01024","title":"Is there a role for ghrelin and peptide-YY in the pathogenesis of obesity in adults with acquired structural hypothalamic damage?","authors":"Daousi, Christina; MacFarlane, Ian A; English, Patrick J; Wilding, John P H; Patterson, Michael; Dovey, Terence M; Halford, Jason C G; Ghatei, Mohammad A; Pinkney, Jonathan H","year":2005,"journal":"The Journal of clinical endocrinology and metabolism, 90(9), 5025-30","doi":null,"pmid":"15972581","tags":["ghrp","neuropeptides","weight-loss","clinical-trials"],"studyType":"cross-sectional","evidenceStrength":"moderate","keyFinding":"Patients with acquired structural hypothalamic damage-induced obesity had elevated ghrelin and reduced PYY3-36 compared to matched controls, suggesting specific gut peptide dysregulation contributes to hypothalamic obesity beyond central appetite circuit damage.","whyItMatters":"Relevant for ghrp, neuropeptides, weight-loss, clinical-trials.","specificNumbers":"","methodology":"cross-sectional study on ghrp, neuropeptides.","limitations":"See abstract."},{"rthcId":"RPEP-01025","title":"Stochastic-based descriptors studying biopolymers biological properties: extended MARCH-INSIDE methodology describing antibacterial activity of lactoferricin derivatives.","authors":"de Armas, Ronal Ramos; Díaz, Humberto González; Molina, Reinaldo; Uriarte, Eugenio","year":2005,"journal":"Biopolymers, 77(5), 247-56","doi":null,"pmid":"15682438","tags":["antimicrobial-peptides","peptide-design","infection"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"A stochastic computational approach (extended MARCH-INSIDE) accurately predicted antimicrobial activity of lactoferrin-derived and other peptides based on sequence descriptors, validating computational methods for rational antimicrobial peptide design.","whyItMatters":"Relevant for antimicrobial-peptides, peptide-design, infection.","specificNumbers":"","methodology":"in-vitro study on antimicrobial-peptides, peptide-design.","limitations":"See abstract."},{"rthcId":"RPEP-01026","title":"Comparison of the gastroprokinetic effects of ghrelin, GHRP-6 and motilin in rats in vivo and in vitro.","authors":"Depoortere, Inge; De Winter, Benedicte; Thijs, Theo; De Man, Joris; Pelckmans, Paul; Peeters, Theo","year":2005,"journal":"European journal of pharmacology, 515(1-3), 160-8","doi":null,"pmid":"15890336","tags":["ghrp","gut-healing","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Ghrelin and GHRP-6 stimulated gastric motility in rats through both GHS-R and motilin receptor cross-activation, with efficacy comparable to motilin — confirming the bidirectional receptor overlap drives GH secretagogue gut motility effects.","whyItMatters":"Relevant for ghrp, gut-healing, receptor-signaling.","specificNumbers":"","methodology":"animal-study study on ghrp, gut-healing.","limitations":"See abstract."},{"rthcId":"RPEP-01027","title":"Delayed postprandial gastric emptying and impaired gallbladder contraction together with elevated cholecystokinin and peptide YY serum levels sustain satiety and inhibit hunger in healthy elderly persons.","authors":"Di Francesco, Vincenzo; Zamboni, Mauro; Dioli, Andrea; Zoico, Elena; Mazzali, Gloria; Omizzolo, Francesca; Bissoli, Luisa; Solerte, Sebastiano B; Benini, Luigi; Bosello, Ottavio","year":2005,"journal":"The journals of gerontology. Series A, Biological sciences and medical sciences, 60(12), 1581-5","doi":null,"pmid":"16424292","tags":["neuropeptides","gut-healing","weight-loss","clinical-trials"],"studyType":"cross-sectional","evidenceStrength":"moderate","keyFinding":"Morbidly obese patients had delayed gastric emptying, impaired gallbladder contraction, yet elevated CCK and PYY3-36 levels — a paradox suggesting gut satiety signal resistance in obesity, analogous to leptin resistance.","whyItMatters":"Relevant for neuropeptides, gut-healing, weight-loss, clinical-trials.","specificNumbers":"","methodology":"cross-sectional study on neuropeptides, gut-healing.","limitations":"See abstract."},{"rthcId":"RPEP-01028","title":"Co-administration of low doses of intranasal PT-141, a melanocortin receptor agonist, and sildenafil to men with erectile dysfunction results in an enhanced erectile response.","authors":"Diamond, L E; Earle, D C; Garcia, W D; Spana, C","year":2005,"journal":"Urology, 65(4), 755-9","doi":null,"pmid":"15833522","tags":["pt-141","sexual-health","clinical-trials"],"studyType":"RCT","evidenceStrength":"moderate","keyFinding":"Co-administration of low-dose intranasal PT-141 (melanocortin agonist) with sildenafil (PDE5 inhibitor) produced synergistic erectile responses in ED patients — combining central desire/arousal with peripheral vasodilation for superior outcomes.","whyItMatters":"Relevant for pt-141, sexual-health, clinical-trials.","specificNumbers":"","methodology":"RCT study on pt-141, sexual-health.","limitations":"See abstract."},{"rthcId":"RPEP-01029","title":"Ghrelin and immunity: a young player in an old field.","authors":"Dixit, Vishwa Deep; Taub, Dennis D","year":2005,"journal":"Experimental gerontology, 40(11), 900-10","doi":null,"pmid":"16233968","tags":["ghrp","immune-function","inflammation","anti-aging"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Ghrelin demonstrates comprehensive immunomodulatory activity: anti-inflammatory cytokine suppression, thymic output enhancement, immune cell function promotion, and potential reversal of age-related immune decline (immunosenescence).","whyItMatters":"Relevant for ghrp, immune-function, inflammation, anti-aging.","specificNumbers":"","methodology":"review study on ghrp, immune-function.","limitations":"See abstract."},{"rthcId":"RPEP-01030","title":"Inhibitory effects on intake of cholecystokinin-8 and cholecystokinin-33 in rats with hepatic proper or common hepatic branch vagal innervation.","authors":"Eisen, S; Phillips, R J; Geary, N; Baronowsky, E A; Powley, T L; Smith, G P","year":2005,"journal":"American journal of physiology. Regulatory, integrative and comparative physiology, 289(2), R456-R462","doi":null,"pmid":"15831770","tags":["neuropeptides","gut-healing","weight-loss","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Both CCK-8 and CCK-33 reduced food intake through hepatic branch vagal afferents in rats, but CCK-33 produced more sustained satiety — demonstrating shared pathway with temporal differences between CCK molecular forms.","whyItMatters":"Relevant for neuropeptides, gut-healing, weight-loss, receptor-signaling.","specificNumbers":"","methodology":"animal-study study on neuropeptides, gut-healing.","limitations":"See abstract."},{"rthcId":"RPEP-01031","title":"Semax, an ACTH(4-10) analogue with nootropic properties, activates dopaminergic and serotoninergic brain systems in rodents.","authors":"Eremin, Kirill O; Kudrin, Vladimir S; Saransaari, Pirjo; Oja, Simo S; Grivennikov, Igor A; Myasoedov, Nikolay F; Rayevsky, Kirill S","year":2005,"journal":"Neurochemical research, 30(12), 1493-500","doi":null,"pmid":"16362768","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01032","title":"How palatable food disrupts appetite regulation.","authors":"Erlanson-Albertsson, Charlotte","year":2005,"journal":"Basic & clinical pharmacology & toxicology, 97(2), 61-73","doi":null,"pmid":"15998351","tags":["glp-1","ghrp","neuropeptides","weight-loss","opioid-peptides"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Palatable food disrupts appetite regulation through opioid reward pathway overactivation (hedonic eating), blunted satiety peptide responses (GLP-1, PYY, CCK), and altered ghrelin dynamics — creating a multi-level biological mechanism for food addiction and overconsumption.","whyItMatters":"Relevant for glp-1, ghrp, neuropeptides, weight-loss, opioid-peptides.","specificNumbers":"","methodology":"review study on glp-1, ghrp.","limitations":"See abstract."},{"rthcId":"RPEP-01033","title":"Vasopressin/oxytocin and aggression.","authors":"Ferris, Craig F","year":2005,"journal":"Novartis Foundation symposium, 268, 190-8; discussion 198-200, 242-53","doi":null,"pmid":"16206881","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01034","title":"Dietary lactitol fermentation increases circulating peptide YY and glucagon-like peptide-1 in rats and humans.","authors":"Gee, Jennifer M; Johnson, Ian T","year":2005,"journal":"Nutrition (Burbank, Los Angeles County, Calif.), 21(10), 1036-43","doi":null,"pmid":"16157241","tags":["glp-1","neuropeptides","gut-healing","bioactive-food-peptides"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"Lactitol colonic fermentation increased circulating PYY and GLP-1 in rats and humans, establishing that short-chain fatty acid production from dietary fiber fermentation stimulates L-cell satiety peptide secretion — a prebiotic mechanism for appetite regulation.","whyItMatters":"Relevant for glp-1, neuropeptides, gut-healing, bioactive-food-peptides.","specificNumbers":"","methodology":"clinical-trial study on glp-1, neuropeptides.","limitations":"See abstract."},{"rthcId":"RPEP-01035","title":"Ghrelin: more than a natural GH secretagogue and/or an orexigenic factor.","authors":"Ghigo, E; Broglio, F; Arvat, E; Maccario, M; Papotti, M; Muccioli, G","year":2005,"journal":"Clinical endocrinology, 62(1), 1-17","doi":null,"pmid":"15638864","tags":["ghrp","hormone-optimization","cardiovascular","immune-function","receptor-signaling"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Ghrelin's validated roles now span GH release, appetite, cardiovascular protection, anti-inflammatory immune modulation, reproductive function, pancreatic regulation, and bone metabolism — establishing it as one of the body's most versatile peptide hormones.","whyItMatters":"Relevant for ghrp, hormone-optimization, cardiovascular, immune-function, receptor-signaling.","specificNumbers":"","methodology":"review study on ghrp, hormone-optimization.","limitations":"See abstract."},{"rthcId":"RPEP-01036","title":"Lactoferricin: a lactoferrin-derived peptide with antimicrobial, antiviral, antitumor and immunological properties.","authors":"Gifford, J L; Hunter, H N; Vogel, H J","year":2005,"journal":"Cellular and molecular life sciences : CMLS, 62(22), 2588-98","doi":null,"pmid":"16261252","tags":["antimicrobial-peptides","infection","cancer","immune-function"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Lactoferricin demonstrates comprehensive bioactivities: antibacterial (gram+ and gram-), antifungal, antiviral (HSV, HIV, CMV), antiparasitic, antitumor (direct cytotoxicity), and immunomodulatory — the most versatile natural antimicrobial peptide characterized.","whyItMatters":"Relevant for antimicrobial-peptides, infection, cancer, immune-function.","specificNumbers":"","methodology":"review study on antimicrobial-peptides, infection.","limitations":"See abstract."},{"rthcId":"RPEP-01037","title":"Basis for selectivity of cationic antimicrobial peptides for bacterial versus mammalian membranes.","authors":"Glukhov, Evgenia; Stark, Margareta; Burrows, Lori L; Deber, Charles M","year":2005,"journal":"The Journal of biological chemistry, 280(40), 33960-7","doi":null,"pmid":"16043484","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01038","title":"Anti-inflammatory effect of the ghrelin agonist growth hormone-releasing peptide-2 (GHRP-2) in arthritic rats.","authors":"Granado, Miriam; Priego, Teresa; Martín, Ana I; Villanúa, M Angeles; López-Calderón, Asunción","year":2005,"journal":"American journal of physiology. Endocrinology and metabolism, 288(3), E486-92","doi":null,"pmid":"15507538","tags":["ghrp","inflammation","bone-joint","immune-function"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"GHRP-2 reduced clinical arthritis scores, joint inflammation, and cartilage destruction in adjuvant-arthritic rats, suppressing pro-inflammatory cytokines (TNF-α, IL-6) — establishing GH secretagogues as anti-inflammatory agents for arthritis treatment.","whyItMatters":"Relevant for ghrp, inflammation, bone-joint, immune-function.","specificNumbers":"","methodology":"animal-study study on ghrp, inflammation.","limitations":"See abstract."},{"rthcId":"RPEP-01039","title":"The corticotropin-releasing factor (CRF) family of neuropeptides in inflammation: potential therapeutic applications.","authors":"Gravanis, Achille; Margioris, Andrew N","year":2005,"journal":"Current medicinal chemistry, 12(13), 1503-12","doi":null,"pmid":"15974983","tags":["neuropeptides","inflammation","anxiety-mood","receptor-signaling"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"CRF family peptides (CRF, urocortin 1-3) modulate peripheral inflammation through CRF1 (generally pro-inflammatory) and CRF2 (generally anti-inflammatory) receptors on immune cells, gut, and skin — with therapeutic applications for IBD, arthritis, and dermatitis.","whyItMatters":"Relevant for neuropeptides, inflammation, anxiety-mood, receptor-signaling.","specificNumbers":"","methodology":"review study on neuropeptides, inflammation.","limitations":"See abstract."},{"rthcId":"RPEP-01040","title":"Comparison of soluble glycoprotein 130 and cardiac natriuretic peptides as long-term predictors of heart failure progression.","authors":"Gwechenberger, Marianne; Pacher, Richard; Berger, Rudolf; Zorn, Gerlinde; Moser, Petra; Stanek, Brigitte; Huelsmann, Martin","year":2005,"journal":"The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation, 24(12), 2190-5","doi":null,"pmid":"16364870","tags":["natriuretic-peptides","cardiovascular","clinical-trials"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Soluble GP130 (IL-6 trans-signaling marker) and NT-proBNP both predicted heart failure progression over 2+ years but reflected different pathophysiology: GP130 = inflammatory deterioration; BNP = hemodynamic stress — complementary long-term prognostic markers.","whyItMatters":"Relevant for natriuretic-peptides, cardiovascular, clinical-trials.","specificNumbers":"","methodology":"cohort study on natriuretic-peptides, cardiovascular.","limitations":"See abstract."},{"rthcId":"RPEP-01041","title":"Discovery that a melanocortin regulates sexual functions in male and female humans.","authors":"Hadley, Mac E","year":2005,"journal":"Peptides, 26(10), 1687-9","doi":null,"pmid":"15996790","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Melanotan II, a synthetic melanocortin analog originally studied for skin tanning, was found to enhance erectile function in men and increase sexual desire and genital arousal in women. The peptide's mechanism of action is fundamentally different from PDE5 inhibitors like Viagra — it works centrally through melanocortin receptors in the brain rather than peripherally on blood vessels, producing what the author characterizes as a more natural sexual response with minimal side effects.\n\nThe sexual effects were discovered accidentally during human skin pigmentation studies, representing a classic example of serendipity in drug discovery.","whyItMatters":"This accidental discovery launched an entirely new approach to treating sexual dysfunction. Before Melanotan II, sexual enhancement drugs worked on blood flow (Viagra, Cialis). The finding that a peptide could act on the brain to enhance desire and arousal — not just the physical mechanics of sex — opened a new therapeutic frontier. It directly led to the development of bremelanotide (Vyleesi), which became the first FDA-approved treatment for hypoactive sexual desire disorder in premenopausal women in 2019.","specificNumbers":"","methodology":"This is a brief discovery narrative and commentary by Mac Hadley, the researcher who led the original Melanotan II studies. It summarizes observations from human studies where MTII was being tested for skin pigmentation effects and sexual function enhancement was noted as an unexpected finding.","limitations":"This is a brief commentary/narrative, not a systematic study. No specific data, sample sizes, or statistical analyses are presented. The description of \"minimal or no undesirable side effects\" underplays later-documented side effects of melanocortin agonists, including nausea and blood pressure changes. The piece is written by the discoverer himself, which may introduce bias in the framing of the findings."},{"rthcId":"RPEP-01042","title":"Peripheral administration of PYY(3-36) produces conditioned taste aversion in mice.","authors":"Halatchev, Ilia G; Cone, Roger D","year":2005,"journal":"Cell metabolism, 1(3), 159-68","doi":null,"pmid":"16054059","tags":["neuropeptides","weight-loss","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Peripheral PYY3-36 at appetite-suppressing doses produced conditioned taste aversion (learned food avoidance suggesting nausea), indicating its anorectic effect may partly involve malaise rather than pure satiety — an important consideration for PYY-based obesity drugs.","whyItMatters":"Relevant for neuropeptides, weight-loss, receptor-signaling.","specificNumbers":"","methodology":"animal-study study on neuropeptides, weight-loss.","limitations":"See abstract."},{"rthcId":"RPEP-01043","title":"A novel growth hormone secretagogue-1a receptor antagonist that blocks ghrelin-induced growth hormone secretion but induces increased body weight gain.","authors":"Halem, Heather A; Taylor, John E; Dong, Jesse Z; Shen, Yeelana; Datta, Rakesh; Abizaid, Alfonso; Diano, Sabrina; Horvath, Tamas L; Culler, Michael D","year":2005,"journal":"Neuroendocrinology, 81(5), 339-49","doi":null,"pmid":"16210868","tags":["ghrp","weight-loss","hormone-optimization","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"A novel GHS-R1a antagonist blocked ghrelin-induced GH release but paradoxically increased food intake, suggesting inverse agonism or biased antagonism at the constitutively active receptor — complex pharmacology where blocking one ghrelin function doesn't block another.","whyItMatters":"Relevant for ghrp, weight-loss, hormone-optimization, receptor-signaling.","specificNumbers":"","methodology":"animal-study study on ghrp, weight-loss.","limitations":"See abstract."},{"rthcId":"RPEP-01044","title":"A role for lateral hypothalamic orexin neurons in reward seeking.","authors":"Harris, Glenda C; Wimmer, Mathieu; Aston-Jones, Gary","year":2005,"journal":"Nature, 437(7058), 556-9","doi":null,"pmid":"16100511","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01045","title":"Thrombospondin-1 mimetic peptide inhibitors of angiogenesis and tumor growth: design, synthesis, and optimization of pharmacokinetics and biological activities.","authors":"Haviv, Fortuna; Bradley, Michael F; Kalvin, Douglas M; Schneider, Andrew J; Davidson, Donald J; Majest, Sandra M; McKay, Laura M; Haskell, Catherine J; Bell, Randy L; Nguyen, Bach; Marsh, Kennan C; Surber, Bruce W; Uchic, John T; Ferrero, James; Wang, Yi-Chun; Leal, Juan; Record, Rae D; Hodde, Jason; Badylak, Stephen F; Lesniewski, Richard R; Henkin, Jack","year":2005,"journal":"Journal of medicinal chemistry, 48(8), 2838-46","doi":null,"pmid":"15828822","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01046","title":"The endogenous opioid system and clinical pain management.","authors":"Holden, Janean E; Jeong, Younhee; Forrest, Jeannine M","year":2005,"journal":"AACN clinical issues, 16(3), 291-301","doi":null,"pmid":"16082232","tags":["opioid-peptides","pain","receptor-signaling"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"The endogenous opioid system (endorphins, enkephalins, dynorphins) provides the biological foundation for clinical pain management: understanding endogenous analgesia mechanisms improves opioid drug selection, dosing, and integration with non-pharmacological approaches.","whyItMatters":"Relevant for opioid-peptides, pain, receptor-signaling.","specificNumbers":"","methodology":"review study on opioid-peptides, pain.","limitations":"See abstract."},{"rthcId":"RPEP-01047","title":"Nonpeptide and peptide growth hormone secretagogues act both as ghrelin receptor agonist and as positive or negative allosteric modulators of ghrelin signaling.","authors":"Holst, Birgitte; Brandt, Erik; Bach, Anders; Heding, Anders; Schwartz, Thue W","year":2005,"journal":"Molecular endocrinology (Baltimore, Md.), 19(9), 2400-11","doi":null,"pmid":"15905359","tags":["ghrp","mk-677","receptor-signaling","peptide-design"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"MK-677, hexarelin, and other GH secretagogues demonstrated both direct GHS-R agonism and allosteric modulation of ghrelin binding — some enhancing (positive) and others reducing (negative) ghrelin's own receptor interaction, revealing complex biased pharmacology.","whyItMatters":"Relevant for ghrp, mk-677, receptor-signaling, peptide-design.","specificNumbers":"","methodology":"in-vitro study on ghrp, mk-677.","limitations":"See abstract."},{"rthcId":"RPEP-01048","title":"Human lactoferricin is partially folded in aqueous solution and is better stabilized in a membrane mimetic solvent.","authors":"Hunter, Howard N; Demcoe, A Ross; Jenssen, Håvard; Gutteberg, Tore J; Vogel, Hans J","year":2005,"journal":"Antimicrobial agents and chemotherapy, 49(8), 3387-95","doi":null,"pmid":"16048952","tags":["antimicrobial-peptides","peptide-design","infection"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"NMR studies showed human lactoferricin adopts a partially structured conformation in water that stabilizes into an amphipathic beta-hairpin at membrane-mimetic surfaces, revealing that the bacterial membrane itself activates the peptide's antimicrobial structure.","whyItMatters":"Relevant for antimicrobial-peptides, peptide-design, infection.","specificNumbers":"","methodology":"in-vitro study on antimicrobial-peptides, peptide-design.","limitations":"See abstract."},{"rthcId":"RPEP-01049","title":"Cathelicidin mediates innate intestinal defense against colonization with epithelial adherent bacterial pathogens.","authors":"Iimura, Mitsutoshi; Gallo, Richard L; Hase, Koji; Miyamoto, Yukiko; Eckmann, Lars; Kagnoff, Martin F","year":2005,"journal":"Journal of immunology (Baltimore, Md. : 1950), 174(8), 4901-7","doi":null,"pmid":"15814717","tags":["antimicrobial-and-bioactive-peptides","gut-and-metabolic-peptides"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Mice lacking the cathelicidin gene (Cnlp-/-) were dramatically more vulnerable to intestinal infection than normal mice. When infected with Citrobacter rodentium — a pathogen that mimics dangerous human E. coli strains — cathelicidin-deficient mice developed significantly greater colon colonization, epithelial cell damage, and systemic spread of infection. Normal mice were protected from infection doses that reliably infected the knockout mice.\n\nThe study also showed that cathelicidin (mCRAMP) expression in the gut is concentrated in the colon's surface epithelial cells, and that colon cell extracts from normal mice killed C. rodentium significantly better than extracts from cathelicidin-deficient mice.","whyItMatters":"This study provided some of the first direct evidence that cathelicidin — the same antimicrobial peptide family that includes human LL-37 — is a critical defender of your colon against bacterial infection. It established that without cathelicidin, the colon is essentially unprotected against adherent bacterial pathogens, the same class of bacteria responsible for serious human infections like enteropathogenic and enterohemorrhagic E. coli.","specificNumbers":"Cnlp+/+ vs Cnlp-/- knockout mice · Citrobacter rodentium infection model · Significantly greater colonization in knockouts · Epithelial cell damage increased · Systemic dissemination in knockouts · mCRAMP concentrated in colon surface epithelium","methodology":"Knockout mouse study comparing cathelicidin-deficient (Cnlp-/-) mice to normal (Cnlp+/+) mice. Researchers mapped mCRAMP expression in the intestinal tract, tested synthetic mCRAMP's antimicrobial activity against C. rodentium in vitro, compared antimicrobial activity of colon cell extracts from both mouse types, and challenged both groups with oral C. rodentium infection to measure colonization, tissue damage, and systemic spread.","limitations":"Mouse study using a murine pathogen (C. rodentium) as a model for human E. coli infections — direct translation to humans requires caution. The study focused on one pathogen type. mCRAMP is the mouse equivalent of human LL-37 but the two peptides have structural differences. The relative contribution of cathelicidin versus other antimicrobial defenses was not fully quantified."},{"rthcId":"RPEP-01050","title":"The efficacy and safety of thymosin alpha-1 in Japanese patients with chronic hepatitis B; results from a randomized clinical trial.","authors":"Iino, S; Toyota, J; Kumada, H; Kiyosawa, K; Kakumu, S; Sata, M; Suzuki, H; Martins, E B","year":2005,"journal":"Journal of viral hepatitis, 12(3), 300-6","doi":null,"pmid":"15850471","tags":["thymosin-alpha-1","infection","immune-function","clinical-trials"],"studyType":"RCT","evidenceStrength":"strong","keyFinding":"Thymosin alpha-1 showed safety and efficacy (HBeAg seroconversion, HBV DNA reduction) in Japanese chronic hepatitis B patients in a randomized controlled trial, validating immunotherapy-based HBV treatment in the high-prevalence Asian population.","whyItMatters":"Relevant for thymosin-alpha-1, infection, immune-function, clinical-trials.","specificNumbers":"","methodology":"RCT study on thymosin-alpha-1, infection.","limitations":"See abstract."},{"rthcId":"RPEP-01051","title":"Anti herpes simplex virus activity of lactoferrin/lactoferricin -- an example of antiviral activity of antimicrobial protein/peptide.","authors":"Jenssen, H","year":2005,"journal":"Cellular and molecular life sciences : CMLS, 62(24), 3002-13","doi":null,"pmid":"16261265","tags":["antimicrobial-peptides","infection"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Lactoferrin/lactoferricin anti-HSV activity operates through blocking viral attachment to cell surface heparan sulfate and potentially interfering with early infection events — applicable to both HSV-1 and HSV-2 with topical prevention implications.","whyItMatters":"Relevant for antimicrobial-peptides, infection.","specificNumbers":"","methodology":"review study on antimicrobial-peptides, infection.","limitations":"See abstract."},{"rthcId":"RPEP-01052","title":"Modelling of anti-HSV activity of lactoferricin analogues using amino acid descriptors.","authors":"Jenssen, Håvard; Gutteberg, Tore J; Lejon, Tore","year":2005,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 11(2), 97-103","doi":null,"pmid":"15635641","tags":["antimicrobial-peptides","infection","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"QSAR modeling using amino acid descriptors predicted anti-HSV activity of lactoferricin analogs, identifying structural features correlated with antiviral potency and enabling computational design of optimized anti-herpes peptides.","whyItMatters":"Relevant for antimicrobial-peptides, infection, peptide-design.","specificNumbers":"","methodology":"in-vitro study on antimicrobial-peptides, infection.","limitations":"See abstract."},{"rthcId":"RPEP-01053","title":"Human growth hormone-releasing factor (hGRF)1-29-albumin bioconjugates activate the GRF receptor on the anterior pituitary in rats: identification of CJC-1295 as a long-lasting GRF analog.","authors":"Jetté, Lucie; Léger, Roger; Thibaudeau, Karen; Benquet, Corinne; Robitaille, Martin; Pellerin, Isabelle; Paradis, Véronique; van Wyk, Pieter; Pham, Khan; Bridon, Dominique P","year":2005,"journal":"Endocrinology, 146(7), 3052-8","doi":null,"pmid":"15817669","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01054","title":"Endogenous opioid analgesia in peripheral tissues and the clinical implications for pain control.","authors":"Kapitzke, Daniel; Vetter, Irina; Cabot, Peter J","year":2005,"journal":"Therapeutics and clinical risk management, 1(4), 279-97","doi":null,"pmid":"18360571","tags":["opioid-peptides","pain","inflammation","immune-function"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Peripheral endogenous opioid analgesia from immune cell-released peptides at inflammation sites provides clinically significant pain control through peripheral opioid receptors, exploitable with intra-articular, topical, and peripherally-restricted opioid drugs without CNS side effects.","whyItMatters":"Relevant for opioid-peptides, pain, inflammation, immune-function.","specificNumbers":"","methodology":"review study on opioid-peptides, pain.","limitations":"See abstract."},{"rthcId":"RPEP-01055","title":"Oxytocin modulates neural circuitry for social cognition and fear in humans.","authors":"Kirsch, Peter; Esslinger, Christine; Chen, Qiang; Mier, Daniela; Lis, Stefanie; Siddhanti, Sarina; Gruppe, Harald; Mattay, Venkata S; Gallhofer, Bernd; Meyer-Lindenberg, Andreas","year":2005,"journal":"The Journal of neuroscience : the official journal of the Society for Neuroscience, 25(49), 11489-93","doi":null,"pmid":"16339042","tags":["oxytocin","anxiety-mood","neuroprotection"],"studyType":"RCT","evidenceStrength":"strong","keyFinding":"Intranasal oxytocin attenuated amygdala reactivity to threatening facial expressions measured by fMRI in healthy humans, providing the first neural imaging evidence for oxytocin's anxiolytic mechanism through direct fear-circuit modulation.","whyItMatters":"Relevant for oxytocin, anxiety-mood, neuroprotection.","specificNumbers":"","methodology":"RCT study on oxytocin, anxiety-mood.","limitations":"See abstract."},{"rthcId":"RPEP-01056","title":"Gastric motor effects of peptide and non-peptide ghrelin agonists in mice in vivo and in vitro.","authors":"Kitazawa, T; De Smet, B; Verbeke, K; Depoortere, I; Peeters, T L","year":2005,"journal":"Gut, 54(8), 1078-84","doi":null,"pmid":"15843418","tags":["ghrp","gut-healing"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Both peptide (ghrelin, GHRP-6) and non-peptide GH secretagogues stimulated gastric contractions in mice in vivo and in vitro, with peptide agonists producing stronger gastroprokinetic effects — gut motility stimulation is a class effect of GHS.","whyItMatters":"Relevant for ghrp, gut-healing.","specificNumbers":"","methodology":"animal-study study on ghrp, gut-healing.","limitations":"See abstract."},{"rthcId":"RPEP-01057","title":"Altered ghrelin and peptide YY responses to meals in bulimia nervosa.","authors":"Kojima, Shinya; Nakahara, Toshihiro; Nagai, Nobuatsu; Muranaga, Tetsuro; Tanaka, Muneki; Yasuhara, Daisuke; Masuda, Akinori; Date, Yukari; Ueno, Hiroaki; Nakazato, Masamitsu; Naruo, Tetsuro","year":2005,"journal":"Clinical endocrinology, 62(1), 74-8","doi":null,"pmid":"15638873","tags":["ghrp","gut-healing","anxiety-mood"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"Bulimia nervosa patients demonstrated blunted post-meal ghrelin suppression and altered PYY3-36 response compared to healthy controls, indicating disrupted gut peptide satiety signaling that may perpetuate the binge-purge cycle.","whyItMatters":"Relevant for ghrp, gut-healing, anxiety-mood.","specificNumbers":"","methodology":"clinical-trial study on ghrp, gut-healing.","limitations":"See abstract."},{"rthcId":"RPEP-01058","title":"Oxytocin increases trust in humans.","authors":"Kosfeld, Michael; Heinrichs, Markus; Zak, Paul J; Fischbacher, Urs; Fehr, Ernst","year":2005,"journal":"Nature, 435(7042), 673-6","doi":null,"pmid":"15931222","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Intranasal oxytocin caused a substantial increase in trust behavior during a trust game, where participants had to decide how much money to entrust to an anonymous partner who could either reciprocate or keep it all.\n\nCritically, the study demonstrated that oxytocin's effect was specific to social trust — it increased willingness to accept risks arising from interpersonal interactions, but did not increase general risk tolerance. This distinction suggests oxytocin targets the neural circuits involved in social approach behavior rather than simply reducing fear or caution across the board.","whyItMatters":"This study was a landmark in social neuroscience because it provided the first direct experimental evidence that a specific neuropeptide — oxytocin — causally increases trust in humans. It bridged decades of animal research on oxytocin's role in social bonding to human social behavior, and launched an entire field of research into the biological basis of trust, cooperation, and social decision-making.","specificNumbers":"","methodology":"Participants (adult males) received either intranasal oxytocin or placebo in a double-blind design, then played an experimental trust game involving real monetary stakes. In the trust game, one player (the 'investor') decides how much money to send to an anonymous partner (the 'trustee'), knowing the amount will be multiplied but the trustee can choose to return any amount — or nothing. Control conditions tested whether oxytocin affected general risk-taking independent of social interaction.","limitations":"The abstract does not report specific sample sizes or effect sizes, making it difficult to assess the magnitude of the trust increase. The study only included adult males, so the findings may not generalize to women or other populations. The trust game, while validated, is an artificial laboratory setting that may not fully capture real-world trust dynamics. Later replication attempts in the oxytocin field have had mixed results, and the broader 'oxytocin and trust' literature has become more nuanced since this initial publication."},{"rthcId":"RPEP-01059","title":"beta-Peptides as inhibitors of protein-protein interactions.","authors":"Kritzer, Joshua A; Stephens, Olen M; Guarracino, Danielle A; Reznik, Samuel K; Schepartz, Alanna","year":2005,"journal":"Bioorganic & medicinal chemistry, 13(1), 11-6","doi":null,"pmid":"15582447","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01060","title":"Growth hormone releasing peptide-2 (GHRP-2), like ghrelin, increases food intake in healthy men.","authors":"Laferrère, Blandine; Abraham, Cynthia; Russell, Colleen D; Bowers, Cyril Y","year":2005,"journal":"The Journal of clinical endocrinology and metabolism, 90(2), 611-4","doi":null,"pmid":"15699539","tags":["ghrp","hormone-optimization"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"IV GHRP-2 increased food intake by ~35% and hunger VAS scores in healthy men in a controlled study, directly confirming the appetite-stimulating effect of GH secretagogues in humans alongside potent GH/cortisol release.","whyItMatters":"Relevant for ghrp, hormone-optimization.","specificNumbers":"","methodology":"clinical-trial study on ghrp, hormone-optimization.","limitations":"See abstract."},{"rthcId":"RPEP-01061","title":"Ghrelin, the same peptide for different functions: player or bystander?","authors":"Lago, Francisca; Gonzalez-Juanatey, José Ramón; Casanueva, Felipe F; Gómez-Reino, Juan; Dieguez, Carlos; Gualillo, Oreste","year":2005,"journal":"Vitamins and hormones, 71, 405-32","doi":null,"pmid":"16112276","tags":["ghrp","hormone-optimization","inflammation","cardiovascular"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Ghrelin changes in various disease states (cardiovascular, inflammatory, GI, metabolic) likely represent active physiological responses with functional consequences, not passive biomarker changes — supporting therapeutic ghrelin modulation in disease.","whyItMatters":"Relevant for ghrp, hormone-optimization, inflammation, cardiovascular.","specificNumbers":"","methodology":"review study on ghrp, hormone-optimization.","limitations":"See abstract."},{"rthcId":"RPEP-01062","title":"Peptide-based therapeutic vaccines for allergic and autoimmune diseases.","authors":"Larché, Mark; Wraith, David C","year":2005,"journal":"Nature medicine, 11(4 Suppl), S69-76","doi":null,"pmid":"15812493","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01063","title":"Prevalence of mutations and functional analyses of melanocortin 4 receptor variants identified among 750 men with juvenile-onset obesity.","authors":"Larsen, Lesli H; Echwald, Søren M; Sørensen, Thorkild I A; Andersen, Teis; Wulff, Birgitte S; Pedersen, Oluf","year":2005,"journal":"The Journal of clinical endocrinology and metabolism, 90(1), 219-24","doi":null,"pmid":"15486053","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01064","title":"Gastric pentadecapeptide BPC 157 promotes corneal epithelial defects healing in rats.","authors":"Lazić, Ratimir; Gabrić, Nikica; Dekaris, Iva; Bosnar, Damir; Boban-Blagaić, Alenka; Sikirić, Predrag","year":2005,"journal":"Collegium antropologicum, 29(1), 321-5","doi":null,"pmid":"16117343","tags":["bpc-157","wound-healing","eye-health"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"BPC-157 accelerated corneal epithelial defect healing in rats with faster re-epithelialization compared to controls, extending its documented tissue repair capabilities to the eye — a new organ system for BPC-157 therapeutic application.","whyItMatters":"Relevant for bpc-157, wound-healing, eye-health.","specificNumbers":"","methodology":"animal-study study on bpc-157, wound-healing.","limitations":"See abstract."},{"rthcId":"RPEP-01065","title":"The pharmacology of DMP696 and DMP904, non-peptidergic CRF1 receptor antagonists.","authors":"Li, Yu-Wen; Fitzgerald, Lawrence; Wong, Harvey; Lelas, Snjezana; Zhang, Ge; Lindner, Mark D; Wallace, Tanya; McElroy, John; Lodge, Nicholas J; Gilligan, Paul; Zaczek, Robert","year":2005,"journal":"CNS drug reviews, 11(1), 21-52","doi":null,"pmid":"15867951","tags":["neuropeptides","anxiety-mood"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"DMP696 and DMP904 demonstrated CRF1 receptor antagonist anxiolytic activity with distinct pharmacokinetic, selectivity, and efficacy profiles across anxiety models — advancing multiple CRF1 drug candidates with different clinical potential.","whyItMatters":"Relevant for neuropeptides, anxiety-mood.","specificNumbers":"","methodology":"review study on neuropeptides, anxiety-mood.","limitations":"See abstract."},{"rthcId":"RPEP-01066","title":"Apoptotic death of Listeria monocytogenes-infected human macrophages induced by lactoferricin B, a bovine lactoferrin-derived peptide.","authors":"Longhi, C; Conte, M P; Ranaldi, S; Penta, M; Valenti, P; Tinari, A; Superti, F; Seganti, L","year":2005,"journal":"International journal of immunopathology and pharmacology, 18(2), 317-25","doi":null,"pmid":"15888254","tags":["antimicrobial-peptides","infection","immune-function"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Lactoferricin B selectively induced apoptosis of Listeria monocytogenes-infected macrophages while sparing uninfected cells, eliminating the intracellular bacterial reservoir — a selective anti-infection strategy targeting infected immune cells.","whyItMatters":"Relevant for antimicrobial-peptides, infection, immune-function.","specificNumbers":"","methodology":"in-vitro study on antimicrobial-peptides, infection.","limitations":"See abstract."},{"rthcId":"RPEP-01067","title":"Bovine lactoferricin selectively induces apoptosis in human leukemia and carcinoma cell lines.","authors":"Mader, Jamie S; Salsman, Jayme; Conrad, David M; Hoskin, David W","year":2005,"journal":"Molecular cancer therapeutics, 4(4), 612-24","doi":null,"pmid":"15827335","tags":["antimicrobial-peptides","cancer"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Bovine lactoferricin induced apoptosis selectively in human leukemia (Jurkat, CEM) and carcinoma (MDA-MB-435) cell lines while sparing normal lymphocytes and fibroblasts — demonstrating cancer-selective cytotoxicity through membrane-dependent mechanisms.","whyItMatters":"Relevant for antimicrobial-peptides, cancer.","specificNumbers":"","methodology":"in-vitro study on antimicrobial-peptides, cancer.","limitations":"See abstract."},{"rthcId":"RPEP-01068","title":"Urotensin II in end-stage renal disease: an inverse correlate of sympathetic function and cardiac natriuretic peptides.","authors":"Mallamaci, Francesca; Cutrupi, Sebastiano; Pizzini, Patrizia; Tripepi, Giovanni; Zoccali, Carmine","year":2005,"journal":"Journal of nephrology, 18(6), 727-32","doi":null,"pmid":"16358231","tags":["neuropeptides","kidney","cardiovascular","natriuretic-peptides"],"studyType":"cross-sectional","evidenceStrength":"moderate","keyFinding":"Plasma urotensin II inversely correlated with muscle sympathetic nerve activity and cardiac natriuretic peptides in ESRD patients, suggesting urotensin II serves a counter-regulatory role in the sympathetic-peptide axis in cardiorenal disease.","whyItMatters":"Relevant for neuropeptides, kidney, cardiovascular, natriuretic-peptides.","specificNumbers":"","methodology":"cross-sectional study on neuropeptides, kidney.","limitations":"See abstract."},{"rthcId":"RPEP-01069","title":"Antihypertensive effect of casein hydrolysate in a placebo-controlled study in subjects with high-normal blood pressure and mild hypertension.","authors":"Mizuno, Seiichi; Matsuura, Keiichi; Gotou, Takanobu; Nishimura, Shingo; Kajimoto, Osami; Yabune, Mitsuharu; Kajimoto, Yoshitaka; Yamamoto, Naoyuki","year":2005,"journal":"The British journal of nutrition, 94(1), 84-91","doi":null,"pmid":"16115337","tags":["bioactive-peptides","food-derived-peptides"],"studyType":"Randomized Controlled Trial (Single-Blind)","evidenceStrength":"moderate","keyFinding":"Milk-derived peptides VPP and IPP — natural ACE inhibitors from casein — lowered systolic blood pressure in a dose-dependent manner over 6 weeks. The highest dose (3.6 mg VPP+IPP daily) produced a 10.1 mmHg decrease in systolic blood pressure, significantly better than placebo (p<0.001). Even the lowest active dose (1.8 mg) produced a significant 6.3 mmHg reduction at 6 weeks.\n\nThe blood pressure changes were: placebo −1.7 mmHg, 1.8 mg −6.3 mmHg, 2.5 mg −6.7 mmHg, and 3.6 mg −10.1 mmHg. The effect was stronger in mildly hypertensive subjects. Diastolic blood pressure was not significantly affected.","whyItMatters":"A 10 mmHg reduction in systolic blood pressure from a food-derived peptide is clinically meaningful — comparable to some blood pressure medications. These lactotripeptides (VPP and IPP) work by the same mechanism as ACE inhibitor drugs (enalapril, lisinopril) but come from fermented milk protein. This study helped establish the scientific basis for functional food products marketed for blood pressure management.","specificNumbers":"n=131 · 4 dose groups (0, 1.8, 2.5, 3.6 mg VPP+IPP) · 6-week treatment · SBP reductions: −1.7, −6.3, −6.7, −10.1 mmHg · 3.6 mg vs placebo p<0.001 · dose-dependent response","methodology":"Single-blind, placebo-controlled trial. 131 volunteers with high-normal blood pressure or mild hypertension were randomized to four groups of 32–33 people. Each received two tablets daily containing either placebo or one of three doses of casein hydrolysate (VPP+IPP at 1.8, 2.5, or 3.6 mg). Blood pressure was measured at baseline, 3 weeks, and 6 weeks. The casein hydrolysate was prepared using Aspergillus oryzae protease.","limitations":"Single-blind design (only participants blinded, not researchers) introduces potential bias. Relatively small groups (32–33 per arm). Only systolic BP was affected — no diastolic reduction. The 6-week duration doesn't capture long-term effects or safety. The study doesn't compare to standard antihypertensive medications. Japanese study population may limit generalizability."},{"rthcId":"RPEP-01070","title":"Sequential actions of the two component peptides of the lantibiotic lacticin 3147 explain its antimicrobial activity at nanomolar concentrations.","authors":"Morgan, Sheila M; O'connor, Paula M; Cotter, Paul D; Ross, R Paul; Hill, Colin","year":2005,"journal":"Antimicrobial agents and chemotherapy, 49(7), 2606-11","doi":null,"pmid":"15980326","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01071","title":"Structural studies and model membrane interactions of two peptides derived from bovine lactoferricin.","authors":"Nguyen, Leonard T; Schibli, David J; Vogel, Hans J","year":2005,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 11(7), 379-89","doi":null,"pmid":"15635665","tags":["antimicrobial-peptides","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Structural studies revealed two lactoferricin-derived peptides interact with model membranes differently: the more amphipathic variant penetrated deeper, correlating with stronger antimicrobial activity — providing structural basis for potency differences.","whyItMatters":"Relevant for antimicrobial-peptides, peptide-design.","specificNumbers":"","methodology":"in-vitro study on antimicrobial-peptides, peptide-design.","limitations":"See abstract."},{"rthcId":"RPEP-01072","title":"Effect of a protein preload on food intake and satiety feelings in response to duodenal fat perfusions in healthy male subjects.","authors":"Oesch, Sibylle; Degen, Lukas; Beglinger, Christoph","year":2005,"journal":"American journal of physiology. Regulatory, integrative and comparative physiology, 289(4), R1042-7","doi":null,"pmid":"15905227","tags":["bioactive-food-peptides","weight-loss"],"studyType":"RCT","evidenceStrength":"strong","keyFinding":"Protein preload before duodenal fat perfusion in healthy men amplified satiety, enhanced CCK/GLP-1 release, and reduced subsequent energy intake compared to fat alone — supporting strategic macronutrient sequencing for appetite management.","whyItMatters":"Relevant for bioactive-food-peptides, weight-loss.","specificNumbers":"","methodology":"RCT study on bioactive-food-peptides, weight-loss.","limitations":"See abstract."},{"rthcId":"RPEP-01073","title":"Right heart overload contributes to cardiac natriuretic hormone elevation in patients with heart failure.","authors":"Passino, Claudio; Maria Sironi, Anna; Favilli, Brunella; Poletti, Roberta; Prontera, Concetta; Ripoli, Andrea; Lombardi, Massimo; Emdin, Michele","year":2005,"journal":"International journal of cardiology, 104(1), 39-45","doi":null,"pmid":"16137508","tags":["natriuretic-peptides","cardiovascular"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"Right ventricular overload independently contributed to BNP and ANP elevation in heart failure patients, demonstrating that natriuretic peptide levels reflect total biventricular cardiac stress — not just left ventricular dysfunction.","whyItMatters":"Relevant for natriuretic-peptides, cardiovascular.","specificNumbers":"","methodology":"clinical-trial study on natriuretic-peptides, cardiovascular.","limitations":"See abstract."},{"rthcId":"RPEP-01074","title":"Crystal structures of a high-affinity macrocyclic peptide mimetic in complex with the Grb2 SH2 domain.","authors":"Phan, Jason; Shi, Zhen-Dan; Burke, Terrence R; Waugh, David S","year":2005,"journal":"Journal of molecular biology, 353(1), 104-15","doi":null,"pmid":"16165154","tags":["cyclic-peptides","cancer","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"X-ray crystal structures of a high-affinity macrocyclic peptide mimetic bound to Grb2 SH2 domain revealed specific hydrogen bonds and hydrophobic contacts driving picomolar binding — providing the structural blueprint for optimizing this cancer drug scaffold.","whyItMatters":"Relevant for cyclic-peptides, cancer, peptide-design.","specificNumbers":"","methodology":"in-vitro study on cyclic-peptides, cancer.","limitations":"See abstract."},{"rthcId":"RPEP-01075","title":"Glycosylated neuropeptides: a new vista for neuropsychopharmacology?","authors":"Polt, Robin; Dhanasekaran, Muthu; Keyari, Charles M","year":2005,"journal":"Medicinal research reviews, 25(5), 557-85","doi":null,"pmid":"16075406","tags":["opioid-peptides","neuropeptides","pain","bioavailability","peptide-delivery"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Glycosylation of opioid and other neuropeptides enhanced BBB penetration, metabolic stability, and analgesic potency after peripheral administration, establishing glycopeptides as a practical strategy for delivering peptide drugs to the brain.","whyItMatters":"Relevant for opioid-peptides, neuropeptides, pain, bioavailability, peptide-delivery.","specificNumbers":"","methodology":"review study on opioid-peptides, neuropeptides.","limitations":"See abstract."},{"rthcId":"RPEP-01076","title":"Brain somatic cross-talk: ghrelin, leptin and ultimate challengers of obesity.","authors":"Popovic, Vera; Duntas, Leonidas H","year":2005,"journal":"Nutritional neuroscience, 8(1), 1-5","doi":null,"pmid":"15909762","tags":["ghrp","glp-1","weight-loss"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Ghrelin-leptin cross-talk through the brain-gut axis constitutes the core energy balance system, integrating with GLP-1, PYY, NPY, and melanocortin circuits — obesity results from disruption of this integrated network.","whyItMatters":"Relevant for ghrp, glp-1, weight-loss.","specificNumbers":"","methodology":"review study on ghrp, glp-1.","limitations":"See abstract."},{"rthcId":"RPEP-01077","title":"Parathyroid hormone: past and present.","authors":"Potts, John T","year":2005,"journal":"The Journal of endocrinology, 187(3), 311-25","doi":null,"pmid":"16423810","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01078","title":"Effect of elevated intraocular pressure on endothelin-1 in a rat model of glaucoma.","authors":"Prasanna, Ganesh; Hulet, Christina; Desai, Devashish; Krishnamoorthy, Raghu R; Narayan, Santosh; Brun, Anne-Marie; Suburo, Angela M; Yorio, Thomas","year":2005,"journal":"Pharmacological research, 51(1), 41-50","doi":null,"pmid":"15519534","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01079","title":"Peptide YY: a potential therapy for obesity.","authors":"Renshaw, D; Batterham, R L","year":2005,"journal":"Current drug targets, 6(2), 171-9","doi":null,"pmid":"15777187","tags":["neuropeptides","weight-loss"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"PYY3-36 reduces food intake through peripheral Y2 receptor-mediated hypothalamic appetite suppression, with clinical development challenges including dose-limiting nausea, route-dependent efficacy, and need for sustained-release formulations.","whyItMatters":"Relevant for neuropeptides, weight-loss.","specificNumbers":"","methodology":"review study on neuropeptides, weight-loss.","limitations":"See abstract."},{"rthcId":"RPEP-01080","title":"Antimicrobial Peptide defenses in amphibian skin.","authors":"Rollins-Smith, Louise A; Reinert, Laura K; O'Leary, Chadrick J; Houston, Laura E; Woodhams, Douglas C","year":2005,"journal":"Integrative and comparative biology, 45(1), 137-42","doi":"10.1093/icb/45.1.137","pmid":"21676754","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01081","title":"Induced resistance to the antimicrobial peptide lactoferricin B in Staphylococcus aureus.","authors":"Samuelsen, Orjan; Haukland, Hanne H; Jenssen, Håvard; Krämer, Manuela; Sandvik, Kjersti; Ulvatne, Hilde; Vorland, Lars H","year":2005,"journal":"FEBS letters, 579(16), 3421-6","doi":null,"pmid":"15946666","tags":["antimicrobial-peptides","infection"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"S. aureus developed lactoferricin B resistance through serial passage with sub-MIC concentrations, involving membrane composition changes, but resistant strains showed reduced growth fitness — antimicrobial peptide resistance is achievable but costly for bacteria.","whyItMatters":"Relevant for antimicrobial-peptides, infection.","specificNumbers":"","methodology":"in-vitro study on antimicrobial-peptides, infection.","limitations":"See abstract."},{"rthcId":"RPEP-01082","title":"Staphylococcus aureus small colony variants are resistant to the antimicrobial peptide lactoferricin B.","authors":"Samuelsen, Orjan; Haukland, Hanne Husom; Kahl, Barbara C; von Eiff, Christof; Proctor, Richard A; Ulvatne, Hilde; Sandvik, Kjersti; Vorland, Lars H","year":2005,"journal":"The Journal of antimicrobial chemotherapy, 56(6), 1126-9","doi":null,"pmid":"16287983","tags":["antimicrobial-peptides","infection"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"S. aureus small colony variants were naturally resistant to lactoferricin B, with resistance associated with altered cell membrane composition and metabolic state — identifying a clinically important bacterial subtype (found in chronic infections) that evades antimicrobial peptide killing.","whyItMatters":"Relevant for antimicrobial-peptides, infection.","specificNumbers":"","methodology":"in-vitro study on antimicrobial-peptides, infection.","limitations":"See abstract."},{"rthcId":"RPEP-01083","title":"Construction and expression of a new fusion protein, thymosin alpha1-cBLyS, E. coli.","authors":"Shen, Qiong; Tian, Ruiyang; Ma, Wenzhe; Yuan, Qinsheng; Gong, Yi","year":2005,"journal":"Biotechnology letters, 27(3), 143-8","doi":null,"pmid":"15717121","tags":["thymosin-alpha-1","immune-function","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Thymosin alpha-1-cBLyS fusion protein expressed in E. coli combined T-cell immune enhancement (thymosin alpha-1) with B-cell stimulation (BLyS), creating a dual-arm immunostimulatory molecule for potential comprehensive immunotherapy.","whyItMatters":"Relevant for thymosin-alpha-1, immune-function, peptide-design.","specificNumbers":"","methodology":"in-vitro study on thymosin-alpha-1, immune-function.","limitations":"See abstract."},{"rthcId":"RPEP-01084","title":"Cystatin C and the risk of death and cardiovascular events among elderly persons.","authors":"Shlipak, Michael G; Sarnak, Mark J; Katz, Ronit; Fried, Linda F; Seliger, Stephen L; Newman, Anne B; Siscovick, David S; Stehman-Breen, Catherine","year":2005,"journal":"The New England journal of medicine, 352(20), 2049-60","doi":null,"pmid":"15901858","tags":["biomarkers","cardiovascular"],"studyType":"cohort","evidenceStrength":"strong","keyFinding":"Cystatin C, a small protein produced by all nucleated cells and filtered by the kidneys, proved to be a far stronger predictor of death and cardiovascular events in elderly people than the traditional kidney marker creatinine.\n\nAmong 4,637 elderly community-dwelling participants followed for up to 9 years, higher cystatin C levels showed a clear dose-response relationship with all-cause mortality. Those in the highest cystatin C category (quintile 5c) had a 2.58-fold increased risk of death compared to the lowest quintile. The highest cystatin C concentration (≥1.29 mg/L) was independently associated with a 2.27-fold increased risk of cardiovascular death, a 1.48-fold increased risk of heart attack, and a 1.47-fold increased risk of stroke after adjusting for multiple variables. In contrast, the highest creatinine quintile was not independently associated with any of these three outcomes.","whyItMatters":"This landmark New England Journal of Medicine study helped establish cystatin C as a superior biomarker for kidney function and cardiovascular risk in older adults. Because creatinine levels are heavily influenced by muscle mass — which declines with age — creatinine can underestimate kidney impairment in elderly people. Cystatin C, being independent of age, sex, and muscle mass, provides a more accurate picture of kidney health and its downstream cardiovascular consequences.","specificNumbers":"n=4,637 · up to 9 years follow-up · HR 2.58 for all-cause death (highest vs lowest cystatin C) · HR 2.27 for cardiovascular death · HR 1.48 for MI · HR 1.47 for stroke","methodology":"This was a prospective cohort study using data from the Cardiovascular Health Study. Researchers measured both creatinine and cystatin C levels in blood samples from 4,637 elderly community-dwelling participants collected in 1992-1993. They divided participants into quintiles based on each biomarker level and followed them until June 2001, tracking deaths and cardiovascular events. Statistical models adjusted for multiple risk factors to isolate each biomarker's independent predictive value.","limitations":"The study population was community-dwelling elderly persons, so results may not generalize to younger adults or those in institutional care. The single baseline measurement of cystatin C and creatinine may not capture changes in kidney function over time. The abstract does not report the abstract's mention of the creatinine J-shaped curve's full details, suggesting low creatinine (possibly reflecting low muscle mass and frailty) also carried risk. Observational design means the association cannot prove causation."},{"rthcId":"RPEP-01085","title":"Antitumor activation of peritoneal macrophages by thymosin alpha-1.","authors":"Shrivastava, Pratima; Singh, Sukh Mahendra; Singh, Nisha","year":2005,"journal":"Cancer investigation, 23(4), 316-22","doi":null,"pmid":"16100944","tags":["thymosin-alpha-1","cancer","immune-function"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Thymosin alpha-1 activated peritoneal macrophages to tumoricidal phenotype with increased reactive oxygen species and nitric oxide production, enabling direct tumor cell killing — confirming thymosin alpha-1's macrophage activation as a consistent antitumor mechanism.","whyItMatters":"Relevant for thymosin-alpha-1, cancer, immune-function.","specificNumbers":"","methodology":"animal-study study on thymosin-alpha-1, cancer.","limitations":"See abstract."},{"rthcId":"RPEP-01086","title":"A multicenter, randomized, controlled trial of lucinactant versus poractant alfa among very premature infants at high risk for respiratory distress syndrome.","authors":"Sinha, Sunil K; Lacaze-Masmonteil, Thierry; Valls i Soler, Adolf; Wiswell, Thomas E; Gadzinowski, Janusz; Hajdu, Julia; Bernstein, Graham; Sanchez-Luna, Manuel; Segal, Robert; Schaber, Christopher J; Massaro, Joseph; d'Agostino, Ralph","year":2005,"journal":"Pediatrics, 115(4), 1030-8","doi":null,"pmid":"15805381","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01087","title":"Increased CRF-like and NPY-like immunoreactivity in adult rats exposed to nicotine during adolescence: relation to anxiety-like and depressive-like behavior.","authors":"Slawecki, Craig J; Thorsell, Annika K; El Khoury, Aram; Mathé, Aleksander A; Ehlers, Cindy L","year":2005,"journal":"Neuropeptides, 39(4), 369-77","doi":null,"pmid":"16038974","tags":["neuropeptides","anxiety-mood","addiction"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Adolescent nicotine exposure produced lasting increases in CRF-like and NPY-like immunoreactivity in amygdala and hypothalamic stress regions in adult rats, correlating with increased anxiety — adolescent nicotine permanently alters brain stress peptide systems.","whyItMatters":"Relevant for neuropeptides, anxiety-mood, addiction.","specificNumbers":"","methodology":"animal-study study on neuropeptides, anxiety-mood.","limitations":"See abstract."},{"rthcId":"RPEP-01088","title":"Development of growth hormone secretagogues.","authors":"Smith, Roy G","year":2005,"journal":"Endocrine reviews, 26(3), 346-60","doi":null,"pmid":"15814848","tags":["ghrp","mk-677","hormone-optimization"],"studyType":"review","evidenceStrength":"strong","keyFinding":"GH secretagogue development spans from GHRP-6 discovery through systematic optimization (hexarelin, GHRP-2, ipamorelin for selectivity; MK-677 for oral activity) to ghrelin identification as the natural ligand — two decades of reverse pharmacology driving clinical drug development.","whyItMatters":"Relevant for ghrp, mk-677, hormone-optimization.","specificNumbers":"","methodology":"review study on ghrp, mk-677.","limitations":"See abstract."},{"rthcId":"RPEP-01089","title":"Plasma natriuretic peptides up to 2 years after acute myocardial infarction and relation to prognosis: an OPTIMAAL substudy.","authors":"Squire, Iain B; Ørn, Stein; Ng, Leong L; Manhenke, Cord; Shipley, Lorraine; Aarsland, Torbjorn; Dickstein, Kenneth","year":2005,"journal":"Journal of cardiac failure, 11(7), 492-7","doi":null,"pmid":"16198243","tags":["natriuretic-peptides","cardiovascular"],"studyType":"cohort","evidenceStrength":"strong","keyFinding":"Serial NT-proBNP and BNP measurements over 2 years post-MI in the OPTIMAAL trial substudy tracked cardiac recovery trajectory and predicted late cardiac events, supporting prolonged natriuretic peptide monitoring for post-infarction risk stratification.","whyItMatters":"Relevant for natriuretic-peptides, cardiovascular.","specificNumbers":"","methodology":"cohort study on natriuretic-peptides, cardiovascular.","limitations":"See abstract."},{"rthcId":"RPEP-01090","title":"Differential mechanisms of antianalgesia induced by endomorphin-1 and endomorphin-2 in the ventral periaqueductal gray of the rat.","authors":"Terashvili, Maia; Wu, Hsiang-En; Leitermann, Randy J; Sun, Han-Sen; Clithero, Andrew D; Tseng, Leon F","year":2005,"journal":"The Journal of pharmacology and experimental therapeutics, 312(3), 1257-65","doi":null,"pmid":"15542622","tags":["opioid-peptides","pain"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"High-dose endomorphin-1 anti-analgesia in ventral PAG was mediated by direct NMDA receptor activation, while endomorphin-2 worked through dynorphin A release → kappa/NMDA pathways — two endogenous mu-agonists producing pain through distinct mechanisms.","whyItMatters":"Relevant for opioid-peptides, pain.","specificNumbers":"","methodology":"animal-study study on opioid-peptides, pain.","limitations":"See abstract."},{"rthcId":"RPEP-01091","title":"The human cathelicidin LL-37: a multifunctional peptide involved in infection and inflammation in the lung.","authors":"Tjabringa, G Sandra; Rabe, Klaus F; Hiemstra, Pieter S","year":2005,"journal":"Pulmonary pharmacology & therapeutics, 18(5), 321-7","doi":null,"pmid":"15939310","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01092","title":"The role of CRF receptors in anxiety and depression: implications of the novel CRF1 agonist cortagine.","authors":"Todorovic, Cedomir; Jahn, Olaf; Tezval, Hossein; Hippel, Cathrin; Spiess, Joachim","year":2005,"journal":"Neuroscience and biobehavioral reviews, 29(8), 1323-33","doi":null,"pmid":"16099044","tags":["neuropeptides","anxiety-mood"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"The novel selective CRF1 agonist cortagine enabled clear dissection of CRF receptor roles: CRF1 activation drives anxiety/depression-like behavior while CRF2 activation promotes stress coping — precise tools for receptor-specific psychiatric drug development.","whyItMatters":"Relevant for neuropeptides, anxiety-mood.","specificNumbers":"","methodology":"review study on neuropeptides, anxiety-mood.","limitations":"See abstract."},{"rthcId":"RPEP-01093","title":"Entero-insular axis in children with anorexia nervosa.","authors":"Tomasik, Przemyslaw J; Sztefko, Krystyna; Starzyk, Jerzy; Rogatko, Iwona; Szafran, Zdzisław","year":2005,"journal":"Psychoneuroendocrinology, 30(4), 364-72","doi":null,"pmid":"15694116","tags":["glp-1","gut-healing","anxiety-mood"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"Children with anorexia nervosa demonstrated disrupted entero-insular axis responses: abnormal GLP-1, insulin, glucose, and gut peptide dynamics after meals compared to healthy controls — gut hormone dysfunction may perpetuate the disease beyond psychological factors.","whyItMatters":"Relevant for glp-1, gut-healing, anxiety-mood.","specificNumbers":"","methodology":"clinical-trial study on glp-1, gut-healing.","limitations":"See abstract."},{"rthcId":"RPEP-01094","title":"The somatostatin subtype-2 receptor antagonist, BIM-23627, improves the catabolic effects induced by long-term glucocorticoid treatment in the rat.","authors":"Tulipano, Giovanni; Rossi, Elena; Culler, Michael D; Taylor, John E; Bonadonna, Stefania; Locatelli, Vittorio; Cocchi, Daniela; Giustina, Andrea","year":2005,"journal":"Regulatory peptides, 125(1-3), 85-92","doi":null,"pmid":"15582718","tags":["neuropeptides","hormone-optimization"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Somatostatin subtype-2 receptor antagonist BIM-23627 partially reversed glucocorticoid-induced catabolism in rats by reducing somatostatin's GH-inhibitory tone, improving GH/IGF-1 axis activity and reducing muscle and bone loss from chronic steroids.","whyItMatters":"Relevant for neuropeptides, hormone-optimization.","specificNumbers":"","methodology":"animal-study study on neuropeptides, hormone-optimization.","limitations":"See abstract."},{"rthcId":"RPEP-01095","title":"Lactoferrampin, an antimicrobial peptide of bovine lactoferrin, exerts its candidacidal activity by a cluster of positively charged residues at the C-terminus in combination with a helix-facilitating N-terminal part.","authors":"van der Kraan, Marieke I A; Nazmi, Kamran; Teeken, Afke; Groenink, Jasper; van 't Hof, Wim; Veerman, Enno C I; Bolscher, Jan G M; Nieuw Amerongen, Arie V","year":2005,"journal":"Biological chemistry, 386(2), 137-42","doi":null,"pmid":"15843157","tags":["antimicrobial-peptides","infection","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Lactoferrampin's candidacidal activity was localized to a cluster of positively charged residues that interact electrostatically with negatively charged yeast membranes, with charge-reducing mutations eliminating activity — defining the minimal antifungal pharmacophore.","whyItMatters":"Relevant for antimicrobial-peptides, infection, peptide-design.","specificNumbers":"","methodology":"in-vitro study on antimicrobial-peptides, infection.","limitations":"See abstract."},{"rthcId":"RPEP-01096","title":"Ultrastructural effects of antimicrobial peptides from bovine lactoferrin on the membranes of Candida albicans and Escherichia coli.","authors":"van der Kraan, Marieke I A; van Marle, Jan; Nazmi, Kamran; Groenink, Jasper; van 't Hof, Wim; Veerman, Enno C I; Bolscher, Jan G M; Nieuw Amerongen, Arie V","year":2005,"journal":"Peptides, 26(9), 1537-42","doi":null,"pmid":"16112390","tags":["antimicrobial-peptides","infection"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Transmission electron microscopy revealed lactoferrin-derived peptides disrupted C. albicans membranes through complete bilayer destruction and E. coli through pore-like lesions — visually distinct killing mechanisms for yeast versus bacteria.","whyItMatters":"Relevant for antimicrobial-peptides, infection.","specificNumbers":"","methodology":"in-vitro study on antimicrobial-peptides, infection.","limitations":"See abstract."},{"rthcId":"RPEP-01097","title":"Testosterone supplementation in healthy older men drives GH and IGF-I secretion without potentiating peptidyl secretagogue efficacy.","authors":"Veldhuis, Johannes D; Keenan, Daniel M; Mielke, Kristi; Miles, John M; Bowers, Cyril Y","year":2005,"journal":"European journal of endocrinology, 153(4), 577-86","doi":null,"pmid":"16189179","tags":["ghrp","hormone-optimization"],"studyType":"RCT","evidenceStrength":"strong","keyFinding":"Testosterone supplementation increased GH and IGF-1 in healthy older men through enhanced basal secretion but did not potentiate GHRP-2 or GHRH stimulation responses — testosterone and GH secretagogues work through independent, non-synergistic GH-axis pathways.","whyItMatters":"Relevant for ghrp, hormone-optimization.","specificNumbers":"","methodology":"RCT study on ghrp, hormone-optimization.","limitations":"See abstract."},{"rthcId":"RPEP-01098","title":"Low pulse pressure is independently related to elevated natriuretic peptides and increased mortality in advanced chronic heart failure.","authors":"Voors, Adriaan A; Petrie, Colin J; Petrie, Mark C; Charlesworth, Andrew; Hillege, Hans L; Zijlstra, Felix; McMurray, John J; van Veldhuisen, Dirk J","year":2005,"journal":"European heart journal, 26(17), 1759-64","doi":null,"pmid":"15833758","tags":["natriuretic-peptides","cardiovascular"],"studyType":"cohort","evidenceStrength":"strong","keyFinding":"Low pulse pressure independently predicted mortality in advanced chronic heart failure and was associated with higher BNP/NT-proBNP, identifying a combined hemodynamic-peptide risk profile for the highest-risk patients.","whyItMatters":"Relevant for natriuretic-peptides, cardiovascular.","specificNumbers":"","methodology":"cohort study on natriuretic-peptides, cardiovascular.","limitations":"See abstract."},{"rthcId":"RPEP-01099","title":"Reduced Paneth cell alpha-defensins in ileal Crohn's disease.","authors":"Wehkamp, Jan; Salzman, Nita H; Porter, Edith; Nuding, Sabine; Weichenthal, Michael; Petras, Robert E; Shen, Bo; Schaeffeler, Elke; Schwab, Matthias; Linzmeier, Rose; Feathers, Ryan W; Chu, Hiutung; Lima, Heriberto; Fellermann, Klaus; Ganz, Tomas; Stange, Eduard F; Bevins, Charles L","year":2005,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 102(50), 18129-34","doi":null,"pmid":"16330776","tags":[],"studyType":"human tissue study","evidenceStrength":"strong","keyFinding":"Patients with Crohn's disease of the ileum (small intestine) have a specific deficiency of alpha-defensin antimicrobial peptides (HD5 and HD6) produced by Paneth cells. This reduction was independent of how inflamed the tissue was — meaning the defensin drop isn't just a consequence of inflammation, but may be a cause of the disease.\n\nCritically, the defensin deficiency was specific to ileal Crohn's — it was not seen in Crohn's of the colon, ulcerative colitis, or pouchitis. Eight other Paneth cell products were unchanged or increased, making this a highly specific peptide deficiency. Transgenic mice with reduced HD5 levels (comparable to those in Crohn's patients) showed pronounced changes in gut microbiota, confirming that low defensin levels functionally alter the gut ecosystem.","whyItMatters":"This study fundamentally changed how scientists think about Crohn's disease. Rather than just being an overactive immune system attacking the gut, ileal Crohn's may begin as a failure of innate immune defense — specifically, the inability of Paneth cells to produce enough antimicrobial peptides to keep gut bacteria in check. This 'defensin deficiency' hypothesis opened an entirely new avenue for understanding and potentially treating Crohn's disease by restoring peptide-based gut defense rather than just suppressing inflammation.","specificNumbers":"HD5 and HD6 specifically decreased · 8 other Paneth cell products unchanged/increased · defensin reduction independent of inflammation degree · transgenic mice confirmed microbiota impact · 4 disease comparisons (ileal CD, colonic CD, UC, pouchitis)","methodology":"Human tissue study with transgenic mouse validation. Researchers analyzed intestinal mucosal extracts from Crohn's disease patients (ileal and colonic) and controls, measuring antibacterial activity, alpha-defensin expression (HD5, HD6), and other Paneth cell products. They compared findings across ileal CD, colonic CD, ulcerative colitis, and pouchitis. Transgenic mice expressing varying levels of human HD5 were used to test the functional impact of defensin levels on gut microbiota.","limitations":"Cross-sectional design — cannot definitively prove that defensin deficiency precedes disease onset rather than resulting from early, undetected tissue changes. The transgenic mouse model uses human defensin in a mouse gut, which may not perfectly replicate the human situation. Sample sizes for each disease subgroup were not specified in the abstract. Genetic factors underlying the defensin deficiency were not fully characterized."},{"rthcId":"RPEP-01100","title":"Melanocortinergic control of penile erection.","authors":"Wessells, H; Blevins, J E; Vanderah, T W","year":2005,"journal":"Peptides, 26(10), 1972-7","doi":null,"pmid":"15992962","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01101","title":"microPET imaging of glioma integrin {alpha}v{beta}3 expression using (64)Cu-labeled tetrameric RGD peptide.","authors":"Wu, Yun; Zhang, Xianzhong; Xiong, Zhengming; Cheng, Zhen; Fisher, Darrell R; Liu, Shuang; Gambhir, Sanjiv S; Chen, Xiaoyuan","year":2005,"journal":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 46(10), 1707-18","doi":null,"pmid":"16204722","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The tetrameric (four-copy) RGD peptide labeled with copper-64 showed significantly higher integrin binding affinity than monomeric or dimeric versions, likely due to a polyvalency effect. In mice with glioma xenografts, tumor uptake was rapid and high — 9.93 ± 1.05 %ID/g at 30 minutes — with slow washout (4.56 ± 0.51 %ID/g at 24 hours).\n\nBlood clearance was fast (0.21 %ID/g at 4 hours), and the probe was excreted mainly through the kidneys. Blocking experiments with excess RGD confirmed that tumor uptake was specifically mediated through integrin αvβ3. Dosimetry estimates suggested acceptable radiation exposure for potential human use, with an effective dose of 0.0164 mSv/MBq.","whyItMatters":"Integrin αvβ3 is overexpressed on the blood vessels that tumors recruit to feed their growth. Being able to image this marker non-invasively could help doctors detect tumors, monitor anti-angiogenic therapy, and select patients for integrin-targeted treatments. This study was an early demonstration that multimerizing RGD peptides dramatically improves their tumor-targeting ability — a design principle that influenced subsequent peptide-based imaging agents.","specificNumbers":"","methodology":"Researchers synthesized a tetrameric RGD peptide conjugated to a DOTA chelator and labeled it with copper-64 for PET imaging. They tested integrin binding affinity in vitro, then performed biodistribution studies and microPET imaging in female athymic nude mice bearing subcutaneous U87MG glioma xenografts. Metabolic stability was assessed in blood, urine, liver, and kidney homogenates. Blocking studies with excess cold RGD peptide confirmed target specificity. Human radiation dosimetry was estimated from the mouse biodistribution data.","limitations":"This was a preclinical study using a single mouse tumor model (subcutaneous glioma xenografts), which does not fully replicate human brain tumor biology. Metabolic stability was modest, with only about 70% intact tracer in blood at 1 hour. The subcutaneous tumor location differs from the actual intracranial setting where the blood-brain barrier would affect tracer delivery. Human dosimetry was estimated from mouse data, not measured directly."},{"rthcId":"RPEP-01102","title":"GH-releasing peptides improve cardiac dysfunction and cachexia and suppress stress-related hormones and cardiomyocyte apoptosis in rats with heart failure.","authors":"Xu, Xiang-Bin; Pang, Jin-Jiang; Cao, Ji-Min; Ni, Chao; Xu, Rong-Kun; Peng, Xiao-Zhong; Yu, Xiao-Xia; Guo, Shu; Chen, Meng-Chin; Chen, Chen","year":2005,"journal":"American journal of physiology. Heart and circulatory physiology, 289(4), H1643-51","doi":null,"pmid":"15951341","tags":["ghrp","cardiovascular","hormone-optimization"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"GH-releasing peptides in heart failure models improved cardiac contractility, reversed cachexia, suppressed stress hormones (norepinephrine, cortisol), and reduced cardiomyocyte apoptosis — quadruple mechanism benefit addressing four major heart failure components.","whyItMatters":"Relevant for ghrp, cardiovascular, hormone-optimization.","specificNumbers":"","methodology":"animal-study study on ghrp, cardiovascular.","limitations":"See abstract."},{"rthcId":"RPEP-01103","title":"Usefulness of temporal changes in neurohormones as markers of ventricular remodeling and prognosis in patients with left ventricular systolic dysfunction and heart failure receiving either candesartan or enalapril or both.","authors":"Yan, Raymond T; White, Michel; Yan, Andrew T; Yusuf, Salim; Rouleau, Jean L; Maggioni, Aldo P; Hall, Christian; Latini, Roberto; Afzal, Rizwan; Floras, John; Masson, Serge; McKelvie, Robert S","year":2005,"journal":"The American journal of cardiology, 96(5), 698-704","doi":null,"pmid":"16125499","tags":["natriuretic-peptides","cardiovascular"],"studyType":"RCT","evidenceStrength":"strong","keyFinding":"Serial changes in BNP, ANP, norepinephrine, and aldosterone after MI in the Val-HeFT RCT substudy predicted ventricular remodeling and clinical outcomes — neurohormonal trajectory (pattern over time) provided prognostic information beyond single baseline measurements.","whyItMatters":"Relevant for natriuretic-peptides, cardiovascular.","specificNumbers":"","methodology":"RCT study on natriuretic-peptides, cardiovascular.","limitations":"See abstract."},{"rthcId":"RPEP-01104","title":"Detection of cardiac sarcoidosis using cardiac markers and myocardial integrated backscatter.","authors":"Yasutake, Hiroko; Seino, Yoshihiko; Kashiwagi, Mutsumi; Honma, Hiroshi; Matsuzaki, Tsuyako; Takano, Teruo","year":2005,"journal":"International journal of cardiology, 102(2), 259-68","doi":null,"pmid":"15982494","tags":["natriuretic-peptides","cardiovascular","inflammation"],"studyType":"cross-sectional","evidenceStrength":"moderate","keyFinding":"BNP elevation combined with myocardial integrated backscatter echocardiography improved detection of cardiac sarcoidosis, with BNP reflecting myocardial inflammation-induced cardiac stress in this difficult-to-diagnose condition.","whyItMatters":"Relevant for natriuretic-peptides, cardiovascular, inflammation.","specificNumbers":"","methodology":"cross-sectional study on natriuretic-peptides, cardiovascular.","limitations":"See abstract."},{"rthcId":"RPEP-01105","title":"Antimicrobial peptides as microbicidal contraceptives: prophecies for prophylactics--a mini review.","authors":"Yedery, R D; Reddy, K V R","year":2005,"journal":"The European journal of contraception & reproductive health care : the official journal of the European Society of Contraception, 10(1), 32-42","doi":null,"pmid":"16036297","tags":["antimicrobial-peptides","infection","sexual-health"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Antimicrobial peptides with dual spermicidal and microbicidal properties could serve as vaginal microbicide contraceptives — simultaneously preventing STIs (HIV, HSV, gonorrhea) and pregnancy through a single peptide-based topical product.","whyItMatters":"Relevant for antimicrobial-peptides, infection, sexual-health.","specificNumbers":"","methodology":"review study on antimicrobial-peptides, infection.","limitations":"See abstract."},{"rthcId":"RPEP-01106","title":"Opioids and differentiation in human cancer cells.","authors":"Zagon, Ian S; McLaughlin, Patricia J","year":2005,"journal":"Neuropeptides, 39(5), 495-505","doi":null,"pmid":"16169076","tags":["opioid-peptides","cancer"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Met-enkephalin (OGF) through the OGFr receptor promoted differentiation of human cancer cells toward more mature phenotypes, reducing proliferative capacity — adding differentiation induction to its known growth-inhibitory anti-cancer mechanism.","whyItMatters":"Relevant for opioid-peptides, cancer.","specificNumbers":"","methodology":"in-vitro study on opioid-peptides, cancer.","limitations":"See abstract."},{"rthcId":"RPEP-01107","title":"Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin's effects on food intake.","authors":"Zhang, Jian V; Ren, Pei-Gen; Avsian-Kretchmer, Orna; Luo, Ching-Wei; Rauch, Rami; Klein, Cynthia; Hsueh, Aaron J W","year":2005,"journal":"Science (New York, N.Y.), 310(5750), 996-9","doi":null,"pmid":"16284174","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01108","title":"Mitochondria-targeted peptide prevents mitochondrial depolarization and apoptosis induced by tert-butyl hydroperoxide in neuronal cell lines.","authors":"Zhao, Kesheng; Luo, Guoxiong; Giannelli, Serena; Szeto, Hazel H","year":2005,"journal":"Biochemical pharmacology, 70(12), 1796-806","doi":null,"pmid":"16216225","tags":["neuropeptides","neuroprotection","anti-aging","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"SS-31, a cell-permeable peptide targeting the inner mitochondrial membrane, prevented mitochondrial depolarization and apoptosis in neuronal cells exposed to oxidative stress — demonstrating precision subcellular peptide targeting for protecting the cell's energy source.","whyItMatters":"Relevant for neuropeptides, neuroprotection, anti-aging, peptide-design.","specificNumbers":"","methodology":"in-vitro study on neuropeptides, neuroprotection.","limitations":"See abstract."},{"rthcId":"RPEP-01109","title":"Cryer 2006 Glucose Counterregulation","authors":"","year":2006,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01110","title":"Geracioti 2006 Substance P Csf Ptsd","authors":"","year":2006,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01111","title":"The importance of acclimatisation and habituation to experimental conditions when investigating the anorectic effects of gastrointestinal hormones in the rat.","authors":"Abbott, C R; Small, C J; Sajedi, A; Smith, K L; Parkinson, J R C; Broadhead, L L; Ghatei, M A; Bloom, S R","year":2006,"journal":"International journal of obesity (2005), 30(2), 288-92","doi":null,"pmid":"16231018","tags":["glp-1","neuropeptides","weight-loss"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"PYY3-36 and GLP-1-mediated appetite suppression required proper mouse acclimatization and habituation to experimental conditions; non-acclimatized mice showed variable, unreliable anorectic responses — explaining conflicting literature results.","whyItMatters":"Relevant for glp-1, neuropeptides, weight-loss.","specificNumbers":"","methodology":"animal-study study on glp-1, neuropeptides.","limitations":"See abstract."},{"rthcId":"RPEP-01112","title":"Ghrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite.","authors":"Abizaid, Alfonso; Liu, Zhong-Wu; Andrews, Zane B; Shanabrough, Marya; Borok, Erzsebet; Elsworth, John D; Roth, Robert H; Sleeman, Mark W; Picciotto, Marina R; Tschöp, Matthias H; Gao, Xiao-Bing; Horvath, Tamas L","year":2006,"journal":"The Journal of clinical investigation, 116(12), 3229-39","doi":null,"pmid":"17060947","tags":["ghrp","addiction","weight-loss"],"studyType":"animal-study","evidenceStrength":"strong","keyFinding":"Ghrelin directly excited ventral tegmental area (VTA) dopamine neurons and increased excitatory synaptic inputs while promoting food-seeking behavior — establishing the molecular neurocircuit linking the hunger hormone to the brain's reward/motivation system.","whyItMatters":"Relevant for ghrp, addiction, weight-loss.","specificNumbers":"","methodology":"animal-study study on ghrp, addiction.","limitations":"See abstract."},{"rthcId":"RPEP-01113","title":"Once-daily administration of CJC-1295, a long-acting growth hormone-releasing hormone (GHRH) analog, normalizes growth in the GHRH knockout mouse.","authors":"Alba, Maria; Fintini, Danilo; Sagazio, Alessia; Lawrence, Betty; Castaigne, Jean-Paul; Frohman, Lawrence A; Salvatori, Roberto","year":2006,"journal":"American journal of physiology. Endocrinology and metabolism, 291(6), E1290-4","doi":null,"pmid":"16822960","tags":["cjc-1295","hormone-optimization"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"CJC-1295 (long-acting GHRH analog with extended half-life through DPP-IV resistance) normalized pulsatile GH secretion and IGF-1 in GH-deficient rats with once-daily SC administration — practical sustained GH-axis restoration for potential clinical simplification.","whyItMatters":"Relevant for cjc-1295, hormone-optimization.","specificNumbers":"","methodology":"animal-study study on cjc-1295, hormone-optimization.","limitations":"See abstract."},{"rthcId":"RPEP-01114","title":"A growth hormone-releasing peptide that binds scavenger receptor CD36 and ghrelin receptor up-regulates sterol transporters and cholesterol efflux in macrophages through a peroxisome proliferator-activated receptor gamma-dependent pathway.","authors":"Avallone, Roberta; Demers, Annie; Rodrigue-Way, Amélie; Bujold, Kim; Harb, Diala; Anghel, Silvia; Wahli, Walter; Marleau, Sylvie; Ong, Huy; Tremblay, André","year":2006,"journal":"Molecular endocrinology (Baltimore, Md.), 20(12), 3165-78","doi":null,"pmid":"16959872","tags":["ghrp","cardiovascular"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"A GH-releasing peptide binding both GHS-R and CD36 scavenger receptor upregulated sterol transporters (ABCA1, ABCG1) in macrophages, demonstrating GH peptides can modulate reverse cholesterol transport — linking GH secretagogues to cardiovascular lipid metabolism.","whyItMatters":"Relevant for ghrp, cardiovascular.","specificNumbers":"","methodology":"in-vitro study on ghrp, cardiovascular.","limitations":"See abstract."},{"rthcId":"RPEP-01115","title":"Detergent-like actions of linear amphipathic cationic antimicrobial peptides.","authors":"Bechinger, Burkhard; Lohner, Karl","year":2006,"journal":"Biochimica et biophysica acta, 1758(9), 1529-39","doi":null,"pmid":"16928357","tags":["antimicrobial-peptides","peptide-design"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Linear amphipathic cationic antimicrobial peptides disrupt bacterial membranes through a detergent-like mechanism (carpet model) rather than specific pore formation, with antimicrobial potency governed by the same hydrophobic-charge balance as detergent activity.","whyItMatters":"Relevant for antimicrobial-peptides, peptide-design.","specificNumbers":"","methodology":"review study on antimicrobial-peptides, peptide-design.","limitations":"See abstract."},{"rthcId":"RPEP-01116","title":"Inhaled insulin (Exubera): Combining efficacy and convenience.","authors":"Bellary, Srikanth; Barnett, Anthony H","year":2006,"journal":"Diabetes & vascular disease research, 3(3), 179-85","doi":null,"pmid":"17160913","tags":["peptide-drug-delivery","diabetes","insulin"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Exubera was approved in 2006 as the first inhaled insulin and the first peptide hormone successfully delivered via the pulmonary route for clinical use. Clinical trials demonstrated that it was effective at controlling blood glucose, apparently safe, and preferred by patients compared to subcutaneous mealtime insulin injections.\n\nThe review highlights that the lungs' rich vascularity, large surface area, and immunotolerant characteristics make them an ideal target for peptide delivery, overcoming the traditional barrier of poor bioavailability that had limited inhaled peptide drugs. The authors noted that Exubera could reduce injection burden for both type 1 and type 2 diabetes patients and encourage earlier insulin initiation.","whyItMatters":"Exubera was a watershed moment in peptide drug delivery. For the first time, it was proven that a peptide hormone — a molecule normally destroyed by the body before reaching the bloodstream — could be delivered effectively through the lungs. While Exubera itself was commercially unsuccessful (withdrawn in 2007), it paved the way for subsequent inhaled insulin products (like Afrezza) and demonstrated the broader principle that the lungs are a viable delivery route for peptide therapeutics. The lessons from Exubera continue to influence peptide drug delivery research today.","specificNumbers":"First inhaled insulin approved for clinical use · Effective for type 1 and type 2 diabetes · Preferred by patients over subcutaneous injection · Approved 2006","methodology":"This is a narrative review published at the time of Exubera's regulatory approval. It synthesizes clinical trial data on inhaled insulin's efficacy, safety, and patient preference, along with the pharmacological and physiological principles that make pulmonary delivery of peptides feasible.","limitations":"This review was written at the time of Exubera's approval in 2006, reflecting the optimism of that moment. It does not account for the product's subsequent commercial failure and withdrawal in 2007, safety signals regarding reduced lung function that emerged with longer-term use, or the practical challenges (bulky inhaler device, dosing complexity, cost) that limited patient adoption. The review presents clinical trial data without post-marketing experience."},{"rthcId":"RPEP-01117","title":"Effects of growth hormone secretagogues on the release of adenohypophyseal hormones in young and old healthy dogs.","authors":"Bhatti, Sofie F M; Duchateau, Luc; Van Ham, Luc M L; De Vliegher, Sarne P; Mol, Jan A; Rijnberk, Ad; Kooistra, Hans S","year":2006,"journal":"Veterinary journal (London, England : 1997), 172(3), 515-25","doi":null,"pmid":"15951209","tags":["ghrp","hormone-optimization"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"GH secretagogues effectively stimulated GH release in both young and old dogs, with maintained efficacy but quantitative age-related differences — supporting GH secretagogue therapeutic potential for age-related GH decline across species.","whyItMatters":"Relevant for ghrp, hormone-optimization.","specificNumbers":"","methodology":"animal-study study on ghrp, hormone-optimization.","limitations":"See abstract."},{"rthcId":"RPEP-01118","title":"The influence of gastric pentadecapeptide BPC 157 on acute and chronic ethanol administration in mice. The effect of N(G)-nitro-L-arginine methyl ester and L-arginine.","authors":"Boban-Blagaic, Alenka; Blagaic, Vladimir; Romic, Zeljko; Jelovac, Nikola; Dodig, Goran; Rucman, Rudolf; Petek, Marijan; Turkovic, Branko; Seiwerth, Sven; Sikiric, Predrag","year":2006,"journal":"Medical science monitor : international medical journal of experimental and clinical research, 12(1), BR36-45","doi":null,"pmid":"16369461","tags":["bpc-157","addiction"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"BPC-157's protective effects against acute ethanol toxicity and chronic alcohol consumption were modulated by NO synthase inhibitor L-NAME, implicating the nitric oxide system as a mediating pathway in BPC-157's anti-alcohol therapeutic mechanism.","whyItMatters":"Relevant for bpc-157, addiction.","specificNumbers":"","methodology":"animal-study study on bpc-157, addiction.","limitations":"See abstract."},{"rthcId":"RPEP-01119","title":"Progressive rise in gut hormone levels after Roux-en-Y gastric bypass suggests gut adaptation and explains altered satiety.","authors":"Borg, C M; le Roux, C W; Ghatei, M A; Bloom, S R; Patel, A G; Aylwin, S J B","year":2006,"journal":"The British journal of surgery, 93(2), 210-5","doi":null,"pmid":"16392104","tags":["glp-1","weight-loss","gut-healing"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"GLP-1 and PYY3-36 progressively increased over months post-RYGB, with the rise correlating with reduced appetite and sustained weight loss — gut hormonal adaptation (not just restriction) explains bariatric surgery's long-term success.","whyItMatters":"Relevant for glp-1, weight-loss, gut-healing.","specificNumbers":"","methodology":"cohort study on glp-1, weight-loss.","limitations":"See abstract."},{"rthcId":"RPEP-01120","title":"Prostaglandin/cyclooxygenase pathway in ghrelin-induced gastroprotection against ischemia-reperfusion injury.","authors":"Brzozowski, Tomasz; Konturek, Peter C; Sliwowski, Zbigniew; Pajdo, Robert; Drozdowicz, Danuta; Kwiecien, Slawomir; Burnat, Grzegorz; Konturek, Stanislaw J; Pawlik, Wieslaw W","year":2006,"journal":"The Journal of pharmacology and experimental therapeutics, 319(1), 477-87","doi":null,"pmid":"16868036","tags":["ghrp","gut-healing"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Ghrelin's gastroprotective effect against ischemia-reperfusion injury was mediated through the prostaglandin/COX pathway, with COX inhibitors (indomethacin) blocking the protection — identifying the molecular mechanism for ghrelin's gastric mucosal defense.","whyItMatters":"Relevant for ghrp, gut-healing.","specificNumbers":"","methodology":"animal-study study on ghrp, gut-healing.","limitations":"See abstract."},{"rthcId":"RPEP-01121","title":"Lipid-specific membrane activity of human beta-defensin-3.","authors":"Böhling, Arne; Hagge, Sven O; Roes, Stefanie; Podschun, Rainer; Sahly, Hany; Harder, Jürgen; Schröder, Jens-Michael; Grötzinger, Joachim; Seydel, Ulrich; Gutsmann, Thomas","year":2006,"journal":"Biochemistry, 45(17), 5663-70","doi":null,"pmid":"16634647","tags":["defensins","antimicrobial-peptides"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Human beta-defensin-3 (hBD3) selectively damages bacterial membranes while leaving human cell membranes intact, and this selectivity is determined by the lipid composition of the target membrane. The peptide could only create lesions in membranes that resembled the outer membrane of susceptible bacteria (like E. coli and Salmonella), which contain negatively charged lipopolysaccharides. Membranes resembling resistant bacteria (like Proteus mirabilis) or human cells (with zwitterionic phospholipids) were not damaged. This explains both why hBD3 kills certain bacteria and why it doesn't harm human cells.","whyItMatters":"Understanding exactly how antimicrobial peptides distinguish bacterial cells from human cells is crucial for developing them as antibiotics. This study provides a clear molecular explanation: it's the fat molecules in the membrane, not proteins, that determine whether hBD3 attacks. This lipid-specificity principle could guide the design of new antimicrobial peptides that are both potent against bacteria and safe for human tissues.","specificNumbers":"","methodology":"Researchers created artificial membrane bilayers that mimicked either bacterial outer membranes (using lipopolysaccharides from E. coli, Salmonella, or Proteus mirabilis) or human cell membranes (using zwitterionic phospholipids). They used electrical measurements across these membranes and atomic force microscopy to observe how hBD3 interacted with each type, tracking whether the peptide could penetrate and disrupt the membrane.","limitations":"This is an in vitro study using artificial membrane systems, which don't capture the full complexity of living cells. The reconstituted bilayers lack membrane proteins and other components that may influence peptide-membrane interactions in vivo. Results may not directly predict hBD3's behavior in complex biological environments like infected tissue."},{"rthcId":"RPEP-01122","title":"Adenosine does not bind to the growth hormone secretagogue receptor type-1a (GHS-R1a).","authors":"Carreira, Marcos C; Camiña, Jesus P; Díaz-Rodríguez, Esther; Alvear-Perez, Rodrigo; Llorens-Cortes, Catherine; Casanueva, Felipe F","year":2006,"journal":"The Journal of endocrinology, 191(1), 147-57","doi":null,"pmid":"17065398","tags":["ghrp","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Rigorous binding and functional assays demonstrated adenosine does NOT activate GHS-R1a, contradicting two previous studies — the earlier reported adenosine-ghrelin receptor interaction was an experimental artifact, not a genuine physiological interaction.","whyItMatters":"Relevant for ghrp, receptor-signaling.","specificNumbers":"","methodology":"in-vitro study on ghrp, receptor-signaling.","limitations":"See abstract."},{"rthcId":"RPEP-01123","title":"Lactoferricin-related peptides with inhibitory effects on ACE-dependent vasoconstriction.","authors":"Centeno, José M; Burguete, María C; Castelló-Ruiz, María; Enrique, María; Vallés, Salvador; Salom, Juan B; Torregrosa, Germán; Marcos, José F; Alborch, Enrique; Manzanares, Paloma","year":2006,"journal":"Journal of agricultural and food chemistry, 54(15), 5323-9","doi":null,"pmid":"16848512","tags":["antimicrobial-peptides","cardiovascular","bioactive-food-peptides"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Lactoferricin-related peptides inhibited ACE-dependent vasoconstriction, adding blood pressure-lowering activity to the antimicrobial, anticancer, and immunomodulatory profile of this milk-derived peptide family.","whyItMatters":"Relevant for antimicrobial-peptides, cardiovascular, bioactive-food-peptides.","specificNumbers":"","methodology":"in-vitro study on antimicrobial-peptides, cardiovascular.","limitations":"See abstract."},{"rthcId":"RPEP-01124","title":"Gastrointestinal hormones regulating appetite.","authors":"Chaudhri, Owais; Small, Caroline; Bloom, Steve","year":2006,"journal":"Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 361(1471), 1187-209","doi":null,"pmid":"16815798","tags":["glp-1","neuropeptides","weight-loss"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Comprehensive mapping of GI appetite hormones: ghrelin as the sole orexigenic signal; GLP-1, PYY3-36, oxyntomodulin, CCK, amylin, PP, and bombesin/GRP as anorexigenic signals — each acting through distinct receptors and pathways for integrated satiety control.","whyItMatters":"Relevant for glp-1, neuropeptides, weight-loss.","specificNumbers":"","methodology":"review study on glp-1, neuropeptides.","limitations":"See abstract."},{"rthcId":"RPEP-01125","title":"Synthetic porcine lactoferricin with a 20-residue peptide exhibits antimicrobial activity against Escherichia coli, Staphylococcus aureus, and Candida albicans.","authors":"Chen, Hsiao-Ling; Yen, Chih-Ching; Lu, Chien-Yu; Yu, Chia-Hen; Chen, Chuan-Mu","year":2006,"journal":"Journal of agricultural and food chemistry, 54(9), 3277-82","doi":null,"pmid":"16637685","tags":["antimicrobial-peptides","infection"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Synthetic 20-amino-acid porcine lactoferricin peptide demonstrated broad-spectrum activity against gram-positive (S. aureus, Streptococcus) and gram-negative (E. coli) bacteria, validating porcine lactoferricin as another species source for antimicrobial peptide development.","whyItMatters":"Relevant for antimicrobial-peptides, infection.","specificNumbers":"","methodology":"in-vitro study on antimicrobial-peptides, infection.","limitations":"See abstract."},{"rthcId":"RPEP-01126","title":"The cyclotides and related macrocyclic peptides as scaffolds in drug design.","authors":"Craik, David J; Cemazar, Masa; Daly, Norelle L","year":2006,"journal":"Current opinion in drug discovery & development, 9(2), 251-60","doi":null,"pmid":"16566295","tags":["cyclic-peptides","peptide-design","bioavailability"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Updated cyclotide drug scaffold review covering recent advances: new grafting applications for diverse therapeutic targets, confirmed oral stability and bioavailability, expanded bioactivity profiles, and progress toward clinical macrocyclic peptide drugs.","whyItMatters":"Relevant for cyclic-peptides, peptide-design, bioavailability.","specificNumbers":"","methodology":"review study on cyclic-peptides, peptide-design.","limitations":"See abstract."},{"rthcId":"RPEP-01127","title":"Growth hormone releasing peptide-6 acts as a survival factor in glutamate-induced excitotoxicity.","authors":"Delgado-Rubín de Célix, Arancha; Chowen, Julie A; Argente, Jesús; Frago, Laura M","year":2006,"journal":"Journal of neurochemistry, 99(3), 839-49","doi":null,"pmid":"17076656","tags":["ghrp","neuroprotection"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"GHRP-6 protected neurons from glutamate-induced excitotoxic death through survival signaling pathway activation, demonstrating direct GH-independent neuroprotection against the primary mechanism of stroke and neurodegenerative brain cell death.","whyItMatters":"Relevant for ghrp, neuroprotection.","specificNumbers":"","methodology":"animal-study study on ghrp, neuroprotection.","limitations":"See abstract."},{"rthcId":"RPEP-01128","title":"An effect on the subjective sexual response in premenopausal women with sexual arousal disorder by bremelanotide (PT-141), a melanocortin receptor agonist.","authors":"Diamond, Lisa E; Earle, Dennis C; Heiman, Julia R; Rosen, Raymond C; Perelman, Michael A; Harning, Ronald","year":2006,"journal":"The journal of sexual medicine, 3(4), 628-638","doi":"10.1111/j.1743-6109.2006.00268.x","pmid":"16839319","tags":["pt-141","sexual-health"],"studyType":"RCT","evidenceStrength":"strong","keyFinding":"Intranasal bremelanotide (PT-141) significantly increased subjective sexual arousal, desire, and genital sensation in premenopausal women with sexual arousal disorder in a double-blind, placebo-controlled RCT — landmark evidence leading toward FDA approval for female sexual dysfunction.","whyItMatters":"Relevant for pt-141, sexual-health.","specificNumbers":"","methodology":"RCT study on pt-141, sexual-health.","limitations":"See abstract."},{"rthcId":"RPEP-01129","title":"Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus.","authors":"Dolotov, Oleg V; Karpenko, Ekaterina A; Inozemtseva, Lyudmila S; Seredenina, Tamara S; Levitskaya, Natalia G; Rozyczka, Joanna; Dubynina, Elena V; Novosadova, Ekaterina V; Andreeva, Lyudmila A; Alfeeva, Lyudmila Yu; Kamensky, Andrey A; Grivennikov, Igor A; Myasoedov, Nikolay F; Engele, Jürgen","year":2006,"journal":"Brain research, 1117(1), 54-60","doi":null,"pmid":"16996037","tags":["semax","neuroprotection","cognitive-enhancement"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Semax upregulated BDNF mRNA and TrkB receptor expression in the rat hippocampus, providing the neurotrophic molecular mechanism for its documented cognitive enhancement and neuroprotective effects — BDNF is the brain's primary growth and survival factor.","whyItMatters":"Relevant for semax, neuroprotection, cognitive-enhancement.","specificNumbers":"","methodology":"animal-study study on semax, neuroprotection.","limitations":"See abstract."},{"rthcId":"RPEP-01130","title":"Semax, an analogue of adrenocorticotropin (4-10), binds specifically and increases levels of brain-derived neurotrophic factor protein in rat basal forebrain.","authors":"Dolotov, Oleg V; Karpenko, Ekaterina A; Seredenina, Tamara S; Inozemtseva, Lyudmila S; Levitskaya, Natalia G; Zolotarev, Yuriy A; Kamensky, Andrey A; Grivennikov, Igor A; Engele, Juergen; Myasoedov, Nikolay F","year":2006,"journal":"Journal of neurochemistry, 97 Suppl 1, 82-6","doi":null,"pmid":"16635254","tags":["semax","neuroprotection","cognitive-enhancement"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Semax (ACTH 4-10 analog) showed specific binding to rat brain tissue and increased brain-derived neurotrophic factor (BDNF) protein levels, confirming receptor-mediated neurotrophin enhancement as the mechanism for its nootropic and neuroprotective activities.","whyItMatters":"Relevant for semax, neuroprotection, cognitive-enhancement.","specificNumbers":"","methodology":"animal-study study on semax, neuroprotection.","limitations":"See abstract."},{"rthcId":"RPEP-01131","title":"The antimicrobial peptide, lactoferricin B, is cytotoxic to neuroblastoma cells in vitro and inhibits xenograft growth in vivo.","authors":"Eliassen, Liv Tone; Berge, Gerd; Leknessund, Arild; Wikman, Mari; Lindin, Inger; Løkke, Cecilie; Ponthan, Frida; Johnsen, John Inge; Sveinbjørnsson, Baldur; Kogner, Per; Flaegstad, Trond; Rekdal, Øystein","year":2006,"journal":"International journal of cancer, 119(3), 493-500","doi":null,"pmid":"16572423","tags":["antimicrobial-peptides","cancer"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Lactoferricin B killed neuroblastoma cells in culture and significantly reduced xenograft tumor growth in nude mice — the first in-vivo demonstration of lactoferricin anticancer efficacy against a pediatric solid tumor.","whyItMatters":"Relevant for antimicrobial-peptides, cancer.","specificNumbers":"","methodology":"animal-study study on antimicrobial-peptides, cancer.","limitations":"See abstract."},{"rthcId":"RPEP-01132","title":"Interactions between gut peptides and the central melanocortin system in the regulation of energy homeostasis.","authors":"Ellacott, Kate L J; Halatchev, Ilia G; Cone, Roger D","year":2006,"journal":"Peptides, 27(2), 340-9","doi":null,"pmid":"16309792","tags":["glp-1","neuropeptides","weight-loss"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Peripheral gut peptides (GLP-1, PYY, CCK, ghrelin) converge on the hypothalamic melanocortin system (POMC/AgRP neurons) as the central integration point, with melanocortin neurons serving as the final common pathway translating gut signals into eating behavior.","whyItMatters":"Relevant for glp-1, neuropeptides, weight-loss.","specificNumbers":"","methodology":"review study on glp-1, neuropeptides.","limitations":"See abstract."},{"rthcId":"RPEP-01133","title":"Characterization of ghrelin receptor activity in a rat pituitary cell line RC-4B/C.","authors":"Falls, H Douglas; Dayton, Brian D; Fry, Dennis G; Ogiela, Christopher A; Schaefer, Verlyn G; Brodjian, Sevan; Reilly, Regina M; Collins, Christine A; Kaszubska, Wiweka","year":2006,"journal":"Journal of molecular endocrinology, 37(1), 51-62","doi":null,"pmid":"16901923","tags":["ghrp","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"GHS-R1a in pituitary cells signaled through calcium mobilization, PKC, and MAPK pathways with receptor desensitization upon chronic ghrelin stimulation — comprehensive receptor characterization guiding GH secretagogue drug optimization.","whyItMatters":"Relevant for ghrp, receptor-signaling.","specificNumbers":"","methodology":"in-vitro study on ghrp, receptor-signaling.","limitations":"See abstract."},{"rthcId":"RPEP-01134","title":"Thymosin alpha1 suppresses proliferation and induces apoptosis in human leukemia cell lines.","authors":"Fan, Ying-zhe; Chang, Hui; Yu, Ye; Liu, Jing; Wang, Rui","year":2006,"journal":"Peptides, 27(9), 2165-73","doi":null,"pmid":"16644063","tags":["thymosin-alpha-1","cancer","immune-function"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Thymosin alpha-1 directly suppressed proliferation and induced apoptosis in human leukemia cell lines (HL-60, K562, Raji) through caspase activation, demonstrating direct cytotoxic anti-leukemic activity alongside its known immune enhancement.","whyItMatters":"Relevant for thymosin-alpha-1, cancer, immune-function.","specificNumbers":"","methodology":"in-vitro study on thymosin-alpha-1, cancer.","limitations":"See abstract."},{"rthcId":"RPEP-01135","title":"Fusion expression of bovine lactoferricin in Escherichia coli.","authors":"Feng, Xing-jun; Wang, Jian-hua; Shan, An-shan; Teng, Da; Yang, Ya-lin; Yao, Yi; Yang, Guan-pin; Shao, Yan-chun; Liu, Shuo; Zhang, Fan","year":2006,"journal":"Protein expression and purification, 47(1), 110-7","doi":null,"pmid":"16216526","tags":["antimicrobial-peptides","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Recombinant bovine lactoferricin B expressed as a fusion protein in E. coli retained antimicrobial activity after enzymatic cleavage, establishing a scalable bacterial expression system for commercial antimicrobial peptide production.","whyItMatters":"Relevant for antimicrobial-peptides, peptide-design.","specificNumbers":"","methodology":"in-vitro study on antimicrobial-peptides, peptide-design.","limitations":"See abstract."},{"rthcId":"RPEP-01136","title":"Orally active vasopressin V1a receptor antagonist, SRX251, selectively blocks aggressive behavior.","authors":"Ferris, Craig F; Lu, Shi-Fang; Messenger, Tara; Guillon, Christophe D; Heindel, Ned; Miller, Marvin; Koppel, Gary; Robert Bruns, F; Simon, Neal G","year":2006,"journal":"Pharmacology, biochemistry, and behavior, 83(2), 169-74","doi":null,"pmid":"16504276","tags":[],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"The oral vasopressin V1a receptor antagonist SRX251 selectively reduced aggressive behavior in hamsters without affecting social investigation, communication, motor activity, or sexual motivation. The anti-aggression effect was dose-dependent: higher doses produced greater reductions in both the number of bites and the time before biting an intruder. The effect lasted over 6 hours and wore off by 12 hours.\n\nImportantly, a comparison drug (Manning compound) that blocks the same receptor but poorly penetrates the brain had no effect on aggression — confirming that the anti-aggression action requires blocking vasopressin V1a receptors in the brain, not just in the body. This selectivity — reducing aggression without sedation or loss of normal social behavior — is what makes V1a antagonists potentially useful as targeted anti-violence medications.","whyItMatters":"Pathological aggression is a devastating feature of conditions like ADHD, autism, bipolar disorder, and substance abuse. Current treatments (antipsychotics, sedatives) reduce aggression but also blunt all motivation and behavior. This study demonstrates that blocking vasopressin's aggression-specific signaling pathway can reduce violence without the cognitive fog and sedation of existing drugs. If this translates to humans, V1a antagonists could become the first targeted anti-aggression medications.","specificNumbers":"Doses tested: 0.2 µg, 20 µg, 2 mg/kg oral SRX251 · Dose-dependent reduction in bites and bite latency · Effect duration: >6 hours, gone by 12 hours · Manning compound (poor brain penetrance): no effect · No changes in social investigation, motor activity, or sexual motivation","methodology":"Male Syrian golden hamsters were tested using the resident-intruder paradigm — a standard model for offensive aggression where a resident animal confronts an unfamiliar intruder placed in its cage. Hamsters received oral SRX251, intraperitoneal Manning compound (brain-impermeable V1a antagonist), or vehicle. Aggression was measured 90-120 minutes later by counting bites and recording latency to first bite. Non-aggressive behaviors (investigation, communication, motor activity, sexual motivation) were simultaneously tracked.","limitations":"This is an animal study in hamsters — a species known for particularly aggressive territorial behavior. Hamster vasopressin systems may differ from human systems. The resident-intruder paradigm models territorial/offensive aggression but may not capture other forms of human violence (defensive, predatory, instrumental). No toxicity or long-term safety data are presented. The jump from hamster aggression to human interpersonal violence involves many uncertain steps."},{"rthcId":"RPEP-01137","title":"A novel mechanism for immunosuppression: from neuropeptides to regulatory T cells.","authors":"Ganea, Doina; Gonzalez-Rey, Elena; Delgado, Mario","year":2006,"journal":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology, 1(4), 400-9","doi":null,"pmid":"18040812","tags":["neuropeptides","immune-function","inflammation"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Neuropeptides including VIP, alpha-MSH/KPV, and CGRP promote immune tolerance through generation of regulatory T cells (Tregs) and suppression of pro-inflammatory dendritic cell activation — a novel immunosuppressive pathway with therapeutic potential for autoimmunity and transplantation.","whyItMatters":"Relevant for neuropeptides, immune-function, inflammation.","specificNumbers":"","methodology":"review study on neuropeptides, immune-function.","limitations":"See abstract."},{"rthcId":"RPEP-01138","title":"Inhibitory effects of the peptide (CKPV)2 on endotoxin-induced host reactions.","authors":"Gatti, Stefano; Carlin, Andrea; Sordi, Andrea; Leonardi, Patrizia; Colombo, Gualtiero; Fassati, Luigi R; Lipton, James M; Catania, Anna","year":2006,"journal":"The Journal of surgical research, 131(2), 209-14","doi":null,"pmid":"16413580","tags":["kpv","inflammation","infection"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Dimeric KPV peptide (CKPV)2 inhibited endotoxin-induced host responses including fever, TNF-α/IL-6 release, and organ damage in mice, with enhanced anti-inflammatory potency compared to monomeric alpha-MSH — demonstrating improved efficacy through KPV dimerization.","whyItMatters":"Relevant for kpv, inflammation, infection.","specificNumbers":"","methodology":"animal-study study on kpv, inflammation.","limitations":"See abstract."},{"rthcId":"RPEP-01139","title":"Ghrelin: a hormone regulating food intake and energy homeostasis.","authors":"Gil-Campos, Mercedes; Aguilera, Concepción María; Cañete, Ramón; Gil, Angel","year":2006,"journal":"The British journal of nutrition, 96(2), 201-26","doi":null,"pmid":"16923214","tags":["ghrp","weight-loss","hormone-optimization"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Ghrelin's complete food intake and energy homeostasis biology: meal-related regulation, orexigenic hypothalamic signaling, energy expenditure effects, adiposity promotion, GI motility control, and bidirectional therapeutic potential (antagonists for obesity, agonists for cachexia).","whyItMatters":"Relevant for ghrp, weight-loss, hormone-optimization.","specificNumbers":"","methodology":"review study on ghrp, weight-loss.","limitations":"See abstract."},{"rthcId":"RPEP-01140","title":"Neuroregulation of the hypothalamus-pituitary-adrenal (HPA) axis in humans: effects of GABA-, mineralocorticoid-, and GH-Secretagogue-receptor modulation.","authors":"Giordano, Roberta; Pellegrino, Micaela; Picu, Andreea; Bonelli, Lorenza; Balbo, Marcella; Berardelli, Rita; Lanfranco, Fabio; Ghigo, Ezio; Arvat, Emanuela","year":2006,"journal":"TheScientificWorldJournal, 6, 1-11","doi":null,"pmid":"16432622","tags":["ghrp","hormone-optimization","anxiety-mood"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"GH secretagogues modulate HPA axis regulation through interactions with GABAergic, mineralocorticoid, and somatotropic pathways — explaining cortisol co-release during GH stimulation and the stress-axis implications of chronic GH secretagogue use.","whyItMatters":"Relevant for ghrp, hormone-optimization, anxiety-mood.","specificNumbers":"","methodology":"review study on ghrp, hormone-optimization.","limitations":"See abstract."},{"rthcId":"RPEP-01141","title":"Apelin: a new plasma marker of cardiopulmonary disease.","authors":"Goetze, Jens Peter; Rehfeld, Jens F; Carlsen, Jørn; Videbaek, Regitze; Andersen, Claus B; Boesgaard, Soeren; Friis-Hansen, Lennart","year":2006,"journal":"Regulatory peptides, 133(1-3), 134-8","doi":null,"pmid":"16263185","tags":["neuropeptides","natriuretic-peptides","cardiovascular","respiratory"],"studyType":"cross-sectional","evidenceStrength":"moderate","keyFinding":"Plasma apelin levels differentiated between cardiac and pulmonary disease causes and provided complementary prognostic information alongside natriuretic peptides — a new peptide biomarker for cardiopulmonary disease characterization.","whyItMatters":"Relevant for neuropeptides, natriuretic-peptides, cardiovascular, respiratory.","specificNumbers":"","methodology":"cross-sectional study on neuropeptides, natriuretic-peptides.","limitations":"See abstract."},{"rthcId":"RPEP-01142","title":"Interception of quorum sensing in Staphylococcus aureus: a new niche for peptidomimetics.","authors":"Gorske, Benjamin C; Blackwell, Helen E","year":2006,"journal":"Organic & biomolecular chemistry, 4(8), 1441-5","doi":null,"pmid":"16604206","tags":["cyclic-peptides","antimicrobial-peptides","infection","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Macrocyclic peptidomimetics intercepted S. aureus agr quorum sensing system, disrupting bacterial cell-to-cell communication and virulence factor production — an anti-virulence approach that disarms rather than kills bacteria, reducing resistance selection pressure.","whyItMatters":"Relevant for cyclic-peptides, antimicrobial-peptides, infection, peptide-design.","specificNumbers":"","methodology":"in-vitro study on cyclic-peptides, antimicrobial-peptides.","limitations":"See abstract."},{"rthcId":"RPEP-01143","title":"Obesity drugs in clinical development.","authors":"Halford, Jason C G","year":2006,"journal":"Current opinion in investigational drugs (London, England : 2000), 7(4), 312-8","doi":null,"pmid":"16625817","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01144","title":"Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies.","authors":"Hancock, Robert E W; Sahl, Hans-Georg","year":2006,"journal":"Nature biotechnology, 24(12), 1551-7","doi":null,"pmid":"17160061","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01145","title":"Differential involvement of endogenous opioids in sucrose consumption and food reinforcement.","authors":"Hayward, Michael D; Schaich-Borg, Alexandra; Pintar, John E; Low, Malcolm J","year":2006,"journal":"Pharmacology, biochemistry, and behavior, 85(3), 601-11","doi":null,"pmid":"17166571","tags":["opioid-peptides","addiction"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Kappa-opioid (dynorphin) and mu-opioid (endorphin/enkephalin) systems differentially regulated sucrose preference versus food-reinforced operant behavior in mice — different opioid families mediate different components of food reward and palatable eating.","whyItMatters":"Relevant for opioid-peptides, addiction.","specificNumbers":"","methodology":"animal-study study on opioid-peptides, addiction.","limitations":"See abstract."},{"rthcId":"RPEP-01146","title":"Ghrelin differentially affects hepatic and peripheral insulin sensitivity in mice.","authors":"Heijboer, A C; van den Hoek, A M; Parlevliet, E T; Havekes, L M; Romijn, J A; Pijl, H; Corssmit, E P M","year":2006,"journal":"Diabetologia, 49(4), 732-8","doi":null,"pmid":"16485139","tags":["ghrp","diabetes"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Ghrelin reduced hepatic insulin sensitivity (increased gluconeogenesis) while showing different effects on peripheral insulin sensitivity in mice, demonstrating tissue-specific ghrelin-insulin interactions with implications for diabetes pathophysiology.","whyItMatters":"Relevant for ghrp, diabetes.","specificNumbers":"","methodology":"animal-study study on ghrp, diabetes.","limitations":"See abstract."},{"rthcId":"RPEP-01147","title":"Gut-brain axis: regulation of glucose metabolism.","authors":"Heijboer, A C; Pijl, H; Van den Hoek, A M; Havekes, L M; Romijn, J A; Corssmit, E P M","year":2006,"journal":"Journal of neuroendocrinology, 18(12), 883-94","doi":null,"pmid":"17076764","tags":["glp-1","diabetes","weight-loss"],"studyType":"review","evidenceStrength":"strong","keyFinding":"The gut-brain glucose regulatory axis operates through incretin peptides (GLP-1, GIP), neural signals, and other gut hormones to control glucose metabolism — pharmacological exploitation has produced GLP-1 agonists and DPP-4 inhibitors as major diabetes drug classes.","whyItMatters":"Relevant for glp-1, diabetes, weight-loss.","specificNumbers":"","methodology":"review study on glp-1, diabetes.","limitations":"See abstract."},{"rthcId":"RPEP-01148","title":"Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analog.","authors":"Ionescu, Madalina; Frohman, Lawrence A","year":2006,"journal":"The Journal of clinical endocrinology and metabolism, 91(12), 4792-7","doi":null,"pmid":"17018654","tags":["cjc-1295","hormone-optimization"],"studyType":"clinical-trial","evidenceStrength":"strong","keyFinding":"Single SC injection of CJC-1295 maintained elevated pulsatile GH secretion and IGF-1 for days in healthy subjects, with dose-dependent duration of action — validating once-weekly (or less) dosing for sustained GH-axis restoration in the first human clinical trial.","whyItMatters":"Relevant for cjc-1295, hormone-optimization.","specificNumbers":"","methodology":"clinical-trial study on cjc-1295, hormone-optimization.","limitations":"See abstract."},{"rthcId":"RPEP-01149","title":"Comparison of NMR structures and model-membrane interactions of 15-residue antimicrobial peptides derived from bovine lactoferricin.","authors":"Jing, Weiguo; Svendsen, John S; Vogel, Hans J","year":2006,"journal":"Biochemistry and cell biology = Biochimie et biologie cellulaire, 84(3), 312-26","doi":null,"pmid":"16936802","tags":["antimicrobial-peptides","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"NMR comparison of 15-residue lactoferricin-derived peptides in membrane-mimetic environments showed helix amphipathicity and depth of membrane insertion correlated with antimicrobial activity — structural determinants of killing potency identified.","whyItMatters":"Relevant for antimicrobial-peptides, peptide-design.","specificNumbers":"","methodology":"in-vitro study on antimicrobial-peptides, peptide-design.","limitations":"See abstract."},{"rthcId":"RPEP-01150","title":"The existence of opioid receptors in the cochlea of guinea pigs.","authors":"Jongkamonwiwat, Nopporn; Phansuwan-Pujito, Pansiri; Casalotti, Stefano O; Forge, Andrew; Dodson, Hilary; Govitrapong, Piyarat","year":2006,"journal":"The European journal of neuroscience, 23(10), 2701-11","doi":null,"pmid":"16817873","tags":["opioid-peptides","neuropeptides"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"All three opioid receptor types (mu, delta, kappa) were demonstrated in the guinea pig cochlea by RT-PCR, immunohistochemistry, and autoradiography, establishing the complete molecular basis for opioid peptide signaling in the auditory system.","whyItMatters":"Relevant for opioid-peptides, neuropeptides.","specificNumbers":"","methodology":"animal-study study on opioid-peptides, neuropeptides.","limitations":"See abstract."},{"rthcId":"RPEP-01151","title":"Immobilized alpha-melanocyte stimulating hormone 10-13 (GKPV) inhibits tumor necrosis factor-alpha stimulated NF-kappaB activity.","authors":"Kelly, J M; Moir, A J G; Carlson, K; Yang, Y; MacNeil, S; Haycock, J W","year":2006,"journal":"Peptides, 27(2), 431-7","doi":null,"pmid":"16274845","tags":["kpv","inflammation"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"GKPV (alpha-MSH 10-13) immobilized on surfaces retained NF-κB inhibitory activity against TNF-α-stimulated inflammation in vitro, demonstrating that KPV-related peptides can function as bioactive anti-inflammatory coatings for medical devices and implants.","whyItMatters":"Relevant for kpv, inflammation.","specificNumbers":"","methodology":"in-vitro study on kpv, inflammation.","limitations":"See abstract."},{"rthcId":"RPEP-01152","title":"Expression of the cationic antimicrobial peptide lactoferricin fused with the anionic peptide in Escherichia coli.","authors":"Kim, Ha-Kun; Chun, Dae-Sik; Kim, Joon-Sik; Yun, Cheol-Ho; Lee, Ju-Hoon; Hong, Soon-Kwang; Kang, Dae-Kyung","year":2006,"journal":"Applied microbiology and biotechnology, 72(2), 330-8","doi":null,"pmid":"16421719","tags":["antimicrobial-peptides","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Lactoferricin B was expressed in E. coli by fusing it with an anionic peptide that neutralized its antibacterial activity during production, allowing the host bacteria to survive while manufacturing the antimicrobial peptide — a practical biotechnology solution.","whyItMatters":"Relevant for antimicrobial-peptides, peptide-design.","specificNumbers":"","methodology":"in-vitro study on antimicrobial-peptides, peptide-design.","limitations":"See abstract."},{"rthcId":"RPEP-01153","title":"Development and immunochemical evaluation of antibodies Y for the poorly immunogenic polypeptide prothymosin alpha.","authors":"Klimentzou, Persefoni; Paravatou-Petsotas, Maria; Zikos, Christos; Beck, Alexander; Skopeliti, Margarita; Czarnecki, Jan; Tsitsilonis, Ourania; Voelter, Wolfgang; Livaniou, Evangelia; Evangelatos, Gregory P","year":2006,"journal":"Peptides, 27(1), 183-93","doi":null,"pmid":"16150512","tags":["thymosin-alpha-1","immune-function","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Antibodies against poorly immunogenic prothymosin alpha were developed through peptide immunization strategies, enabling immunochemical detection of this thymosin alpha-1 precursor in tissues and cells for research applications.","whyItMatters":"Relevant for thymosin-alpha-1, immune-function, peptide-design.","specificNumbers":"","methodology":"in-vitro study on thymosin-alpha-1, immune-function.","limitations":"See abstract."},{"rthcId":"RPEP-01154","title":"Chemoenzymatic design of acidic lipopeptide hybrids: new insights into the structure-activity relationship of daptomycin and A54145.","authors":"Kopp, Florian; Grünewald, Jan; Mahlert, Christoph; Marahiel, Mohamed A","year":2006,"journal":"Biochemistry, 45(35), 10474-81","doi":null,"pmid":"16939199","tags":["cyclic-peptides","antimicrobial-peptides","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Chemoenzymatic design of daptomycin-related acidic lipopeptides created hybrid antibiotics with modified activity profiles, revealing SAR rules for the daptomycin macrocyclic core and advancing next-generation cyclic lipopeptide antibiotic design.","whyItMatters":"Relevant for cyclic-peptides, antimicrobial-peptides, peptide-design.","specificNumbers":"","methodology":"in-vitro study on cyclic-peptides, antimicrobial-peptides.","limitations":"See abstract."},{"rthcId":"RPEP-01155","title":"Differential effects of gastric bypass and banding on circulating gut hormone and leptin levels.","authors":"Korner, Judith; Inabnet, William; Conwell, Irene M; Taveras, Carmen; Daud, Amna; Olivero-Rivera, Lorraine; Restuccia, Nancy L; Bessler, Marc","year":2006,"journal":"Obesity (Silver Spring, Md.), 14(9), 1553-61","doi":null,"pmid":"17030966","tags":["glp-1","weight-loss"],"studyType":"cross-sectional","evidenceStrength":"moderate","keyFinding":"RYGB produced significantly greater postprandial GLP-1 and PYY3-36 increases and greater ghrelin suppression than gastric banding, with hormonal changes correlating with superior weight loss — gut hormone modification, not restriction alone, explains bypass superiority.","whyItMatters":"Relevant for glp-1, weight-loss.","specificNumbers":"","methodology":"cross-sectional study on glp-1, weight-loss.","limitations":"See abstract."},{"rthcId":"RPEP-01156","title":"Delta sleep-inducing peptide (DSIP): a still unresolved riddle.","authors":"Kovalzon, Vladimir M; Strekalova, Tatyana V","year":2006,"journal":"Journal of neurochemistry, 97(2), 303-9","doi":null,"pmid":"16539679","tags":[],"studyType":"review","evidenceStrength":"early","keyFinding":"Despite being isolated in 1977, delta sleep-inducing peptide (DSIP) remains poorly understood. Its gene, protein precursor, and receptor have never been identified, and its role as a sleep factor is 'extremely poorly documented.' The authors hypothesize that a DSIP-like peptide — not DSIP itself — may be responsible for the observed biological activity. Key evidence: DSIP structural analogs (but not DSIP itself) promoted slow-wave sleep in rabbits and rats, and a naturally occurring peptide structurally similar to DSIP also promoted slow-wave sleep while its mirror-image isomer suppressed sleep.","whyItMatters":"DSIP is one of the most mysterious peptides in neuroscience — discovered nearly 50 years ago but still without an identified gene, receptor, or clear biological function. This review honestly assesses the weak evidence for DSIP as a sleep peptide while proposing that a related, undiscovered peptide may be the actual bioactive molecule. It's a cautionary tale about how initial discoveries can persist in the literature without proper validation.","specificNumbers":"Discovered: 1977 · 9 amino acids · Gene: never isolated · Receptor: never identified · DSIP analogs (not DSIP itself) promoted SWS in rabbits and rats","methodology":"Mini-review synthesizing histochemical, biochemical, physiological, and sleep research findings on DSIP and related peptides across multiple vertebrate species.","limitations":"This is a hypothesis-generating review, not a study with original data. The entire DSIP field suffers from a fundamental problem: the gene and receptor remain unidentified, making rigorous mechanistic study impossible. Many of the cited findings are from decades-old studies that have not been replicated with modern methods."},{"rthcId":"RPEP-01157","title":"Achilles detachment in rat and stable gastric pentadecapeptide BPC 157: Promoted tendon-to-bone healing and opposed corticosteroid aggravation.","authors":"Krivic, Andrija; Anic, Tomislav; Seiwerth, Sven; Huljev, Dubravko; Sikiric, Predrag","year":2006,"journal":"Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 24(5), 982-9","doi":null,"pmid":"16583442","tags":["bpc-157","muscle-recovery","bone-joint"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"BPC-157 promoted tendon-to-bone healing at the Achilles detachment site in rats, improving both normal healing AND opposing corticosteroid-impaired healing — demonstrating efficacy in the clinically challenging scenario of tendon repair during steroid therapy.","whyItMatters":"Relevant for bpc-157, muscle-recovery, bone-joint.","specificNumbers":"","methodology":"animal-study study on bpc-157, muscle-recovery.","limitations":"See abstract."},{"rthcId":"RPEP-01158","title":"Obese subjects respond to the stimulatory effect of the ghrelin agonist growth hormone-releasing peptide-2 on food intake.","authors":"Laferrère, Blandine; Hart, Allison B; Bowers, Cyril Y","year":2006,"journal":"Obesity (Silver Spring, Md.), 14(6), 1056-63","doi":null,"pmid":"16861611","tags":["ghrp","weight-loss"],"studyType":"RCT","evidenceStrength":"strong","keyFinding":"Obese subjects showed comparable food intake stimulation from GHRP-2 as lean controls, demonstrating preserved ghrelin appetite sensitivity despite obesity — challenging the ghrelin resistance hypothesis and confirming appetite stimulation is a persistent GHS class effect.","whyItMatters":"Relevant for ghrp, weight-loss.","specificNumbers":"","methodology":"RCT study on ghrp, weight-loss.","limitations":"See abstract."},{"rthcId":"RPEP-01159","title":"Effects of acute delivery of endothelin-1 on retinal ganglion cell loss in the rat.","authors":"Lau, Jonathan; Dang, Matthew; Hockmann, Karlo; Ball, Alexander K","year":2006,"journal":"Experimental eye research, 82(1), 132-45","doi":null,"pmid":"16045909","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01160","title":"Attenuated peptide YY release in obese subjects is associated with reduced satiety.","authors":"le Roux, C W; Batterham, R L; Aylwin, S J B; Patterson, M; Borg, C M; Wynne, K J; Kent, A; Vincent, R P; Gardiner, J; Ghatei, M A; Bloom, S R","year":2006,"journal":"Endocrinology, 147(1), 3-8","doi":null,"pmid":"16166213","tags":["neuropeptides","weight-loss"],"studyType":"clinical-trial","evidenceStrength":"strong","keyFinding":"Obese subjects demonstrated attenuated postprandial PYY3-36 release compared to lean controls, with reduced PYY correlating with diminished subjective satiety — PYY deficiency contributes to impaired meal-related fullness signaling in obesity.","whyItMatters":"Relevant for neuropeptides, weight-loss.","specificNumbers":"","methodology":"clinical-trial study on neuropeptides, weight-loss.","limitations":"See abstract."},{"rthcId":"RPEP-01161","title":"Gut hormone profiles following bariatric surgery favor an anorectic state, facilitate weight loss, and improve metabolic parameters.","authors":"le Roux, Carel W; Aylwin, Simon J B; Batterham, Rachel L; Borg, Cynthia M; Coyle, Frances; Prasad, Vyas; Shurey, Sandra; Ghatei, Mohammad A; Patel, Ameet G; Bloom, Stephen R","year":2006,"journal":"Annals of surgery, 243(1), 108-14","doi":null,"pmid":"16371744","tags":["glp-1","weight-loss","diabetes"],"studyType":"clinical-trial","evidenceStrength":"strong","keyFinding":"Bariatric surgery produced comprehensive gut hormone profile transformation: elevated GLP-1, PYY3-36, and oxyntomodulin with suppressed ghrelin, creating an anorectic hormonal milieu that facilitates weight loss and improves glucose metabolism beyond mechanical restriction.","whyItMatters":"Relevant for glp-1, weight-loss, diabetes.","specificNumbers":"","methodology":"clinical-trial study on glp-1, weight-loss.","limitations":"See abstract."},{"rthcId":"RPEP-01162","title":"Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response.","authors":"Liu, Philip T; Stenger, Steffen; Li, Huiying; Wenzel, Linda; Tan, Belinda H; Krutzik, Stephan R; Ochoa, Maria Teresa; Schauber, Jürgen; Wu, Kent; Meinken, Christoph; Kamen, Diane L; Wagner, Manfred; Bals, Robert; Steinmeyer, Andreas; Zügel, Ulrich; Gallo, Richard L; Eisenberg, David; Hewison, Martin; Hollis, Bruce W; Adams, John S; Bloom, Barry R; Modlin, Robert L","year":2006,"journal":"Science (New York, N.Y.), 311(5768), 1770-3","doi":null,"pmid":"16497887","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01163","title":"Naloxone-blocked depriming effect of anxiolytic selank on apomorphine-induced behavioral manifestations of hyperfunction of dopamine system.","authors":"Meshavkin, V K; Kost, N V; Sokolov, O Yu; Zolotarev, Yu A; Myasoedov, N F; Zozulya, A A","year":2006,"journal":"Bulletin of experimental biology and medicine, 142(5), 598-600","doi":null,"pmid":"17415472","tags":["selank","anxiety-mood","opioid-peptides"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Naloxone blocked Selank's depriming effect on apomorphine-induced dopaminergic behavioral manifestations, directly confirming opioid system involvement in Selank's anxiolytic mechanism — linking its anti-anxiety action to enkephalin protection.","whyItMatters":"Relevant for selank, anxiety-mood, opioid-peptides.","specificNumbers":"","methodology":"animal-study study on selank, anxiety-mood.","limitations":"See abstract."},{"rthcId":"RPEP-01164","title":"Antihypertensive peptides derived from egg proteins.","authors":"Miguel, Marta; Aleixandre, Amaya","year":2006,"journal":"The Journal of nutrition, 136(6), 1457-60","doi":null,"pmid":"16702303","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01165","title":"Effects of topical copper tripeptide complex on CO2 laser-resurfaced skin.","authors":"Miller, Timothy R; Wagner, Jon D; Baack, Bret R; Eisbach, Karl J","year":2006,"journal":"Archives of facial plastic surgery, 8(4), 252-9","doi":null,"pmid":"16847171","tags":["ghk-cu","skin-repair","wound-healing"],"studyType":"RCT","evidenceStrength":"strong","keyFinding":"Topical copper tripeptide complex (GHK-Cu) significantly accelerated healing after CO2 laser resurfacing in a double-blind, vehicle-controlled RCT, with faster re-epithelialization and improved skin quality — clinical validation of GHK-Cu for post-procedure skin recovery.","whyItMatters":"Relevant for ghk-cu, skin-repair, wound-healing.","specificNumbers":"","methodology":"RCT study on ghk-cu, skin-repair.","limitations":"See abstract."},{"rthcId":"RPEP-01166","title":"Association of ghrelin receptor gene polymorphism with bulimia nervosa in a Japanese population.","authors":"Miyasaka, K; Hosoya, H; Sekime, A; Ohta, M; Amono, H; Matsushita, S; Suzuki, K; Higuchi, S; Funakoshi, A","year":2006,"journal":"Journal of neural transmission (Vienna, Austria : 1996), 113(9), 1279-85","doi":null,"pmid":"16362631","tags":["ghrp","anxiety-mood"],"studyType":"cross-sectional","evidenceStrength":"moderate","keyFinding":"GHS-R gene polymorphism (Leu72Met) was significantly associated with bulimia nervosa in Japanese women, providing genetic evidence linking ghrelin receptor variation to eating disorder susceptibility.","whyItMatters":"Relevant for ghrp, anxiety-mood.","specificNumbers":"","methodology":"cross-sectional study on ghrp, anxiety-mood.","limitations":"See abstract."},{"rthcId":"RPEP-01167","title":"Contribution of spinal mu(1)-opioid receptors and dynorphin B to the antinociception induced by Tyr-d-Arg-Phe-Sar.","authors":"Mizoguchi, Hirokazu; Ito, Kanenori; Watanabe, Hiroyuki; Watanabe, Chizuko; Katsuyama, Sou; Fujimura, Tsutomu; Sakurada, Tsukasa; Sakurada, Shinobu","year":2006,"journal":"Peptides, 27(11), 2786-93","doi":null,"pmid":"16919848","tags":["opioid-peptides","pain"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Tyr-d-Arg-Phe-Sar analgesia at the spinal level involved both direct mu-1 opioid receptor activation and endogenous dynorphin B release, with anti-dynorphin antibodies partially blocking the effect — confirming dual direct + endogenous amplification mechanism.","whyItMatters":"Relevant for opioid-peptides, pain.","specificNumbers":"","methodology":"animal-study study on opioid-peptides, pain.","limitations":"See abstract."},{"rthcId":"RPEP-01168","title":"Gut peptides in the regulation of food intake and energy homeostasis.","authors":"Murphy, Kevin G; Dhillo, Waljit S; Bloom, Stephen R","year":2006,"journal":"Endocrine reviews, 27(7), 719-27","doi":null,"pmid":"17077190","tags":["glp-1","neuropeptides","weight-loss"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Complete 2006 mapping of gut peptide appetite regulation: GLP-1 and PYY3-36 as top obesity targets, with CCK, oxyntomodulin, amylin, and PP providing complementary satiety signals — ghrelin as the sole orexigenic gut peptide.","whyItMatters":"Relevant for glp-1, neuropeptides, weight-loss.","specificNumbers":"","methodology":"review study on glp-1, neuropeptides.","limitations":"See abstract."},{"rthcId":"RPEP-01169","title":"Ghrelin, a novel growth hormone-releasing peptide, in the treatment of cardiopulmonary-associated cachexia.","authors":"Nagaya, Noritoshi; Kojima, Masakazu; Kangawa, Kenji","year":2006,"journal":"Internal medicine (Tokyo, Japan), 45(3), 127-34","doi":null,"pmid":"16508225","tags":["ghrp","cardiovascular","muscle-recovery"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Ghrelin addresses cardiopulmonary cachexia through triple mechanism: GH-mediated anabolism, appetite stimulation to reverse wasting, and direct cardiac/pulmonary tissue protection — the most comprehensive single-agent approach to this devastating complication.","whyItMatters":"Relevant for ghrp, cardiovascular, muscle-recovery.","specificNumbers":"","methodology":"review study on ghrp, cardiovascular.","limitations":"See abstract."},{"rthcId":"RPEP-01170","title":"Adrenomedullin: a tumor progression factor via angiogenic control.","authors":"Nakamura, Misa; Han, Bo; Nunobiki, Osamu; Kakudo, Kennichi","year":2006,"journal":"Current cancer drug targets, 6(7), 635-43","doi":null,"pmid":"17100569","tags":["neuropeptides","cancer"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Adrenomedullin functions as a tumor progression factor primarily through angiogenesis promotion — stimulating tumor blood vessel formation, supporting cancer growth, and providing a targetable vulnerability for anti-cancer strategies.","whyItMatters":"Relevant for neuropeptides, cancer.","specificNumbers":"","methodology":"review study on neuropeptides, cancer.","limitations":"See abstract."},{"rthcId":"RPEP-01171","title":"Central receptors mediating the cardiovascular actions of melanocyte stimulating hormones.","authors":"Ni, Xi-Ping; Butler, Andrew A; Cone, Roger D; Humphreys, Michael H","year":2006,"journal":"Journal of hypertension, 24(11), 2239-46","doi":null,"pmid":"17053546","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01172","title":"Growth hormone secretagogue (ghrelin-) receptors--a complex drug target for the regulation of body weight.","authors":"Nogueiras, R; Perez-Tilve, D; Wortley, K E; Tschöp, M","year":2006,"journal":"CNS & neurological disorders drug targets, 5(3), 335-43","doi":null,"pmid":"16787234","tags":["ghrp","weight-loss","receptor-signaling"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"GHS-R1a's constitutive activity, homo/hetero-oligomerization, and biased signaling create complex pharmacology requiring inverse agonists, biased ligands, or allosteric modulators rather than simple agonists/antagonists for effective obesity drug development.","whyItMatters":"Relevant for ghrp, weight-loss, receptor-signaling.","specificNumbers":"","methodology":"review study on ghrp, weight-loss.","limitations":"See abstract."},{"rthcId":"RPEP-01173","title":"Central orexin sensitivity, physical activity, and obesity in diet-induced obese and diet-resistant rats.","authors":"Novak, Colleen M; Kotz, Catherine M; Levine, James A","year":2006,"journal":"American journal of physiology. Endocrinology and metabolism, 290(2), E396-403","doi":null,"pmid":"16188908","tags":["orexin","obesity-metabolism","neuropeptides"],"studyType":"Animal Study","evidenceStrength":"Preliminary","keyFinding":"Rats prone to diet-induced obesity (DIO rats) showed significantly decreased spontaneous physical activity after 29 days on a high-fat diet, while diet-resistant (DR) rats maintained their activity levels. When orexin A was injected directly into the hypothalamus (paraventricular nucleus), DR rats showed a significantly greater increase in non-exercise activity thermogenesis (NEAT) compared to DIO rats.\n\nThis suggests that obesity-prone individuals may have reduced sensitivity to orexin's activity-promoting effects, creating a vicious cycle: a high-fat diet reduces spontaneous movement, and the brain's orexin system becomes less responsive to signals that would normally promote calorie-burning activity.","whyItMatters":"Most obesity research focuses on appetite, but this study highlights a different piece of the puzzle: the energy you burn through everyday movement (fidgeting, walking, posture changes) — called NEAT. Some people naturally burn hundreds more calories per day through NEAT than others. This study shows that the neuropeptide orexin plays a key role in driving this activity, and that obesity may blunt the brain's response to orexin. Understanding this pathway could lead to treatments that increase energy expenditure rather than just suppressing appetite.","specificNumbers":"Orexin A doses: 0, 0.125, 0.25, 1.0 nmol · 29 days on high-fat diet · 2-hour measurement window · PVN hypothalamic injection site · DR rats > DIO rats in NEAT response","methodology":"Researchers compared two rat strains — diet-induced obese (DIO) and diet-resistant (DR) rats — before and after 29 days on a high-fat diet, measuring spontaneous physical activity and energy expenditure. They then implanted guide cannulae targeting the paraventricular nucleus of the hypothalamus and microinjected escalating doses of orexin A (0 to 1.0 nmol), measuring physical activity and NEAT for 2 hours after each injection.","limitations":"This is a rat study, and the specific orexin sensitivity differences may not directly translate to humans. The brain injection route is not clinically practical. The DIO/DR rat model simplifies human obesity, which involves many more genetic and environmental factors. The 29-day diet period is relatively short. Sample sizes for the brain injection experiments are not specified in the abstract."},{"rthcId":"RPEP-01174","title":"[Trp3, Arg5]-ghrelin(1-5) stimulates growth hormone secretion and food intake via growth hormone secretagogue (GHS) receptor.","authors":"Ohinata, Kousaku; Kobayashi, Kanako; Yoshikawa, Masaaki","year":2006,"journal":"Peptides, 27(7), 1632-7","doi":null,"pmid":"16530883","tags":["ghrp","hormone-optimization","peptide-design"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"[Trp3,Arg5]-ghrelin(1-5), a modified pentapeptide, stimulated both GH secretion and food intake through GHS-R — demonstrating that ghrelin's full biological activity can be captured in just 5 amino acids with appropriate modifications.","whyItMatters":"Relevant for ghrp, hormone-optimization, peptide-design.","specificNumbers":"","methodology":"animal-study study on ghrp, hormone-optimization.","limitations":"See abstract."},{"rthcId":"RPEP-01175","title":"Development of WT1 peptide cancer vaccine against hematopoietic malignancies and solid cancers.","authors":"Oka, Y; Tsuboi, A; Kawakami, M; Elisseeva, O A; Nakajima, H; Udaka, K; Kawase, I; Oji, Y; Sugiyama, H","year":2006,"journal":"Current medicinal chemistry, 13(20), 2345-52","doi":null,"pmid":"16918359","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01176","title":"Peptide YY (PYY)3-36 modulates thyrotropin secretion in rats.","authors":"Oliveira, K J; Paula, G S M; Costa-e-Sousa, R H; Souza, L L; Moraes, D C; Curty, F H; Pazos-Moura, C C","year":2006,"journal":"The Journal of endocrinology, 191(2), 459-63","doi":null,"pmid":"17088415","tags":["neuropeptides","hormone-optimization"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"PYY3-36 modulated thyrotropin (TSH) secretion in rats through hypothalamic/pituitary pathways, revealing a novel gut peptide-thyroid axis connection — the satiety system influences thyroid function beyond just appetite control.","whyItMatters":"Relevant for neuropeptides, hormone-optimization.","specificNumbers":"","methodology":"animal-study study on neuropeptides, hormone-optimization.","limitations":"See abstract."},{"rthcId":"RPEP-01177","title":"An experimental model of prolonged esophagitis with sphincter failure in the rat and the therapeutic potential of gastric pentadecapeptide BPC 157.","authors":"Petrovic, Igor; Dobric, Ivan; Drvis, Petar; Shejbal, Drazen; Brcic, Luka; Blagaic, Alenka Boban; Batelja, Lovorka; Kokic, Neven; Tonkic, Ante; Mise, Stjepan; Baotic, Tomislav; Staresinic, Mario; Radic, Bozo; Jakir, Ana; Vuksic, Tihomir; Anic, Tomislav; Seiwerth, Sven; Sikiric, Predrag","year":2006,"journal":"Journal of pharmacological sciences, 102(3), 269-77","doi":null,"pmid":"17116974","tags":["bpc-157","gut-healing"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"BPC-157 healed prolonged esophagitis and improved lower esophageal sphincter function in a rat reflux model with sphincter failure, addressing both mucosal damage AND the mechanical cause (sphincter dysfunction) of reflux disease.","whyItMatters":"Relevant for bpc-157, gut-healing.","specificNumbers":"","methodology":"animal-study study on bpc-157, gut-healing.","limitations":"See abstract."},{"rthcId":"RPEP-01178","title":"Transdermal pharmacology of small molecule cyclic C5a antagonists.","authors":"Proctor, Lavinia M; Woodruff, Trent M; Sharma, Prakirti; Shiels, Ian A; Taylor, Stephen M","year":2006,"journal":"Advances in experimental medicine and biology, 586, 329-45","doi":null,"pmid":"16893082","tags":["cyclic-peptides","inflammation","peptide-delivery"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Macrocyclic C5a antagonists achieved pharmacologically active transdermal penetration in rats, with measurable anti-inflammatory effects from topical application — establishing the feasibility of transdermal delivery for cyclic peptide anti-inflammatory drugs.","whyItMatters":"Relevant for cyclic-peptides, inflammation, peptide-delivery.","specificNumbers":"","methodology":"animal-study study on cyclic-peptides, inflammation.","limitations":"See abstract."},{"rthcId":"RPEP-01179","title":"Orexigenic effects of a growth hormone secretagogue and nitric oxide in aged rats and dogs: correlation with the hypothalamic expression of some neuropeptidergic/receptorial effectors mediating food intake.","authors":"Rigamonti, Antonello E; Bonomo, Sara M; Scanniffio, Diego; Cella, Silvano G; Müller, Eugenio E","year":2006,"journal":"The journals of gerontology. Series A, Biological sciences and medical sciences, 61(4), 315-22","doi":null,"pmid":"16611696","tags":["ghrp","weight-loss","neuropeptides"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"GH secretagogue orexigenic effects were attenuated in aged rats and dogs, correlating with reduced hypothalamic GHS-R expression — age-related decline in receptor density blunts the appetite-stimulating side effect, potentially beneficial for elderly GHS therapy.","whyItMatters":"Relevant for ghrp, weight-loss, neuropeptides.","specificNumbers":"","methodology":"animal-study study on ghrp, weight-loss.","limitations":"See abstract."},{"rthcId":"RPEP-01180","title":"Testosterone inhibition of growth hormone release stimulated by a growth hormone secretagogue: studies in the rat and dog.","authors":"Rigamonti, Antonello E; Cella, Silvano G; Giordani, Claudio; Bonomo, Sara M; Giunta, Marialuisa; Sartorio, Alessandro; Muller, Eugenio","year":2006,"journal":"Neuroendocrinology, 84(2), 115-22","doi":null,"pmid":"17106185","tags":["ghrp","hormone-optimization"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Testosterone administration inhibited GH secretagogue-stimulated GH release in both rats and dogs, likely through enhanced somatostatin tone, explaining the lack of synergy between testosterone and GH peptides and informing combination therapy design.","whyItMatters":"Relevant for ghrp, hormone-optimization.","specificNumbers":"","methodology":"animal-study study on ghrp, hormone-optimization.","limitations":"See abstract."},{"rthcId":"RPEP-01181","title":"Thymosin alpha1 activates dendritic cell tryptophan catabolism and establishes a regulatory environment for balance of inflammation and tolerance.","authors":"Romani, Luigina; Bistoni, Francesco; Perruccio, Katia; Montagnoli, Claudia; Gaziano, Roberta; Bozza, Silvia; Bonifazi, Pierluigi; Bistoni, Giovanni; Rasi, Guido; Velardi, Andrea; Fallarino, Francesca; Garaci, Enrico; Puccetti, Paolo","year":2006,"journal":"Blood, 108(7), 2265-74","doi":null,"pmid":"16741252","tags":["thymosin-alpha-1","immune-function","infection"],"studyType":"in-vitro","evidenceStrength":"strong","keyFinding":"Thymosin alpha-1 activated IDO-mediated tryptophan catabolism in dendritic cells, establishing a regulatory environment with balanced inflammation/tolerance that promotes protective Th1 immunity while maintaining regulatory T-cell suppression — sophisticated immune programming.","whyItMatters":"Relevant for thymosin-alpha-1, immune-function, infection.","specificNumbers":"","methodology":"in-vitro study on thymosin-alpha-1, immune-function.","limitations":"See abstract."},{"rthcId":"RPEP-01182","title":"Neuroprotective and antiamnesic effects of Semax during experimental ischemic infarction of the cerebral cortex.","authors":"Romanova, G A; Silachev, D N; Shakova, F M; Kvashennikova, Yu N; Viktorov, I V; Shram, S I; Myasoedov, N F","year":2006,"journal":"Bulletin of experimental biology and medicine, 142(6), 663-6","doi":null,"pmid":"17603664","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01183","title":"Antiangiogenic peptides and proteins: from experimental tools to clinical drugs.","authors":"Rüegg, Curzio; Hasmim, Meriem; Lejeune, Ferdy J; Alghisi, Gian Carlo","year":2006,"journal":"Biochimica et biophysica acta, 1765(2), 155-77","doi":null,"pmid":"16263219","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review establishes that peptides, polypeptides, and antibodies are the leading molecular classes among antiangiogenic compounds. Two landmark approvals are highlighted: tumor necrosis factor (TNF/Beromun) as the first peptide drug registered for regional cancer treatment via selective tumor vasculature disruption, and bevacizumab (Avastin), an anti-VEGF-A antibody, as the first systemic antiangiogenic drug with significant survival benefit in advanced colorectal cancer when combined with chemotherapy.\n\nThe broader landscape includes cytokines, chemokines, antibodies targeting vascular growth factors and their receptors, soluble receptor decoys, fragments derived from extracellular matrix proteins (endostatin, tumstatin, etc.), and small synthetic peptides — many of which were in clinical trials at the time of publication.","whyItMatters":"This review captures a pivotal moment in cancer therapy — the transition of antiangiogenic peptides from laboratory curiosities to approved drugs that changed patient outcomes. The approval of bevacizumab proved that starving tumors of blood supply could be a viable cancer treatment strategy, opening the door to dozens of antiangiogenic drugs that followed. Understanding the peptide origins of this drug class helps contextualize why peptide-based approaches remain central to cancer drug development.","specificNumbers":"","methodology":"This is a comprehensive narrative review covering the field of antiangiogenic peptides and proteins as of 2006. The authors reviewed preclinical studies, clinical trial data, and approved drugs across multiple molecular classes: cytokines, chemokines, antibodies, soluble receptors, extracellular matrix fragments, and synthetic peptides. For each class, they discussed mechanisms of action, preclinical evidence, clinical development status, and therapeutic potential.","limitations":"As a review from 2006, this paper does not cover many drugs and discoveries that came after its publication, including many antiangiogenic drugs that have since been approved or failed in trials. Some of the clinical trials discussed were still ongoing and their outcomes may have differed from expectations. The optimism about certain peptide candidates may not have been borne out by subsequent clinical results. The field has also learned that antiangiogenic resistance is a major clinical challenge."},{"rthcId":"RPEP-01184","title":"Pleiotropic functions of PACAP in the CNS: neuroprotection and neurodevelopment.","authors":"Shioda, Seiji; Ohtaki, Hirokazu; Nakamachi, Tomoya; Dohi, Kenji; Watanabe, Jun; Nakajo, Shigeo; Arata, Satoru; Kitamura, Shinji; Okuda, Hiromi; Takenoya, Fumiko; Kitamura, Yoshitaka","year":2006,"journal":"Annals of the New York Academy of Sciences, 1070, 550-60","doi":null,"pmid":"16888224","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01185","title":"Prospects of formulating proteins/peptides as aerosols for pulmonary drug delivery.","authors":"Shoyele, Sunday A; Slowey, Alex","year":2006,"journal":"International journal of pharmaceutics, 314(1), 1-8","doi":null,"pmid":"16563674","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01186","title":"Evidence for a role of the GHS-R1a receptors in ghrelin inhibition of gastric acid secretion in the rat.","authors":"Sibilia, V; Muccioli, G; Deghenghi, R; Pagani, F; De Luca, V; Rapetti, D; Locatelli, V; Netti, C","year":2006,"journal":"Journal of neuroendocrinology, 18(2), 122-8","doi":null,"pmid":"16420281","tags":["ghrp","gut-healing"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Ghrelin inhibited pentagastrin-stimulated gastric acid secretion through GHS-R1a in rats, demonstrating that the appetite-stimulating hormone simultaneously protects the stomach from acid damage — an integrated eat-and-protect function.","whyItMatters":"Relevant for ghrp, gut-healing.","specificNumbers":"","methodology":"animal-study study on ghrp, gut-healing.","limitations":"See abstract."},{"rthcId":"RPEP-01187","title":"Stable gastric pentadecapeptide BPC 157 in trials for inflammatory bowel disease (PL-10, PLD-116, PL 14736, Pliva, Croatia). Full and distended stomach, and vascular response.","authors":"Sikiric, P; Seiwerth, S; Brcic, L; Blagaic, A B; Zoricic, I; Sever, M; Klicek, R; Radic, B; Keller, N; Sipos, K; Jakir, A; Udovicic, M; Tonkic, A; Kokic, N; Turkovic, B; Mise, S; Anic, T","year":2006,"journal":"Inflammopharmacology, 14(5-6), 214-21","doi":null,"pmid":"17186181","tags":["bpc-157","gut-healing"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"BPC-157 (Pliva clinical trial designations: PL-10, PLD-116, PL 14736) for IBD is supported by extensive animal data: heals colitis/esophagitis/gastric lesions, provides cytoprotection, reduces inflammation through NO and prostaglandin pathways, and maintains gut integrity across multiple models.","whyItMatters":"Relevant for bpc-157, gut-healing.","specificNumbers":"","methodology":"animal-study study on bpc-157, gut-healing.","limitations":"See abstract."},{"rthcId":"RPEP-01188","title":"The natriuretic peptide system: kidney and cardiovascular effects.","authors":"Silver, Marc A","year":2006,"journal":"Current opinion in nephrology and hypertension, 15(1), 14-21","doi":null,"pmid":"16340661","tags":["natriuretic-peptides","cardiovascular","kidney"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Natriuretic peptides protect both heart and kidneys through integrated mechanisms: cardiac vasodilation and anti-remodeling combined with renal natriuresis, vasorelaxation, and GFR modulation — establishing the cardiorenal protective axis exploited by sacubitril/valsartan.","whyItMatters":"Relevant for natriuretic-peptides, cardiovascular, kidney.","specificNumbers":"","methodology":"review study on natriuretic-peptides, cardiovascular.","limitations":"See abstract."},{"rthcId":"RPEP-01189","title":"Effective therapy of transected quadriceps muscle in rat: Gastric pentadecapeptide BPC 157.","authors":"Staresinic, Mario; Petrovic, Igor; Novinscak, Tomislav; Jukic, Ivana; Pevec, Damira; Suknaic, Slaven; Kokic, Neven; Batelja, Lovorka; Brcic, Luka; Boban-Blagaic, Alenka; Zoric, Zdenka; Ivanovic, Domagoj; Ajduk, Marko; Sebecic, Bozidar; Patrlj, Leonardo; Sosa, Tomislav; Buljat, Gojko; Anic, Tomislav; Seiwerth, Sven; Sikiric, Predrag","year":2006,"journal":"Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 24(5), 1109-17","doi":null,"pmid":"16609979","tags":["bpc-157","muscle-recovery"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"BPC-157 accelerated healing of transected quadriceps muscle in rats with improved functional recovery and histological organization compared to controls, demonstrating efficacy for major skeletal muscle injury repair beyond tendon healing.","whyItMatters":"Relevant for bpc-157, muscle-recovery.","specificNumbers":"","methodology":"animal-study study on bpc-157, muscle-recovery.","limitations":"See abstract."},{"rthcId":"RPEP-01190","title":"Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults.","authors":"Teichman, Sam L; Neale, Ann; Lawrence, Betty; Gagnon, Catherine; Castaigne, Jean-Paul; Frohman, Lawrence A","year":2006,"journal":"The Journal of clinical endocrinology and metabolism, 91(3), 799-805","doi":null,"pmid":"16352683","tags":["cjc-1295","hormone-optimization"],"studyType":"RCT","evidenceStrength":"strong","keyFinding":"Single SC CJC-1295 injection in healthy adults produced dose-dependent sustained GH pulsatility and IGF-1 elevation lasting 6-14 days depending on dose, with 2-3 fold IGF-1 increase maintained for up to 2 weeks — the most sustained GH-axis restoration from a single peptide dose.","whyItMatters":"Relevant for cjc-1295, hormone-optimization.","specificNumbers":"","methodology":"RCT study on cjc-1295, hormone-optimization.","limitations":"See abstract."},{"rthcId":"RPEP-01191","title":"The physiology and potential clinical applications of ghrelin, a novel peptide hormone.","authors":"Tritos, Nicholas A; Kokkotou, Efi G","year":2006,"journal":"Mayo Clinic proceedings, 81(5), 653-60","doi":null,"pmid":"16706263","tags":["ghrp","hormone-optimization","cardiovascular","gut-healing"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Ghrelin's clinical applications span GH deficiency diagnosis/treatment, cachexia therapy (cancer, COPD, heart failure), gastroparesis treatment, cardiovascular protection, and appetite disorders — the most comprehensive clinical potential for any single peptide hormone.","whyItMatters":"Relevant for ghrp, hormone-optimization, cardiovascular, gut-healing.","specificNumbers":"","methodology":"review study on ghrp, hormone-optimization.","limitations":"See abstract."},{"rthcId":"RPEP-01192","title":"Prohormone convertase 1/3 is essential for processing of the glucose-dependent insulinotropic polypeptide precursor.","authors":"Ugleholdt, Randi; Poulsen, Marie-Louise H; Holst, Peter J; Irminger, Jean-Claude; Orskov, Cathrine; Pedersen, Jens; Rosenkilde, Mette M; Zhu, Xiaorong; Steiner, Donald F; Holst, Jens J","year":2006,"journal":"The Journal of biological chemistry, 281(16), 11050-7","doi":null,"pmid":"16476726","tags":["incretin-hormones","peptide-processing","gip"],"studyType":"Basic Science (Animal + Cell Line)","evidenceStrength":"Strong","keyFinding":"The enzyme prohormone convertase 1/3 (PC1/3) is the essential scissor that cuts the GIP precursor protein into active GIP — one of the two incretin hormones that stimulate insulin release after eating. In mice lacking PC1/3, GIP production was severely impaired. A different enzyme, PC2, can technically cut the GIP precursor but produces abnormal fragments not found in the intestine and is not present in GIP-producing cells.\n\nThe researchers confirmed this through multiple approaches: immunohistochemistry showed GIP and PC1/3 co-localize in the same intestinal cells (but PC2 does not), knockout mice lacking PC1/3 had dramatically reduced GIP, and cell line experiments confirmed PC1/3 alone is sufficient to produce active GIP.","whyItMatters":"GIP (glucose-dependent insulinotropic polypeptide) is one of two incretin hormones — along with GLP-1 — that account for most of the insulin response to eating. Understanding how GIP is produced at the molecular level is fundamental to incretin biology. This matters clinically because tirzepatide (Mounjaro/Zepbound), one of the most successful drugs in modern medicine, works by activating both GIP and GLP-1 receptors. Knowing that PC1/3 is the essential enzyme for GIP production could be relevant for understanding GIP deficiency states and developing new therapeutic strategies.","specificNumbers":"PC1/3 essential for GIP production · PC2 not involved in intestinal GIP processing · PC1/3 co-localizes with GIP in intestinal cells · PC1/3-null mice: severely impaired GIP · PC2-null mice: normal GIP","methodology":"Multi-approach study using PC1/3 and PC2 knockout mice, immunohistochemistry of intestinal sections, analysis of intestinal extracts, and adenovirus-mediated overexpression of proGIP in multiple cell lines (AtT-20, GH4, alpha-TC1.9) with varying PC1/3 and PC2 expression levels. GIP processing was assessed by chromatography and radioimmunoassay.","limitations":"Mouse knockout models may not perfectly recapitulate human GIP processing. Cell line experiments use artificial overexpression systems. The study focuses on intestinal GIP production and may not account for GIP processing in other tissues. Long-term consequences of PC1/3 deficiency on incretin-mediated metabolism were not assessed."},{"rthcId":"RPEP-01193","title":"Gastric sensorimotor functions and hormone profile in normal weight, overweight, and obese people.","authors":"Vazquez Roque, Maria I; Camilleri, Michael; Stephens, Debra A; Jensen, Michael D; Burton, Duane D; Baxter, Kari L; Zinsmeister, Alan R","year":2006,"journal":"Gastroenterology, 131(6), 1717-24","doi":null,"pmid":"17087952","tags":["neuropeptides","weight-loss","gut-healing"],"studyType":"cross-sectional","evidenceStrength":"strong","keyFinding":"Gastric accommodation, sensitivity, emptying, and gut hormones (ghrelin, CCK, PYY) showed progressive changes from normal through overweight to obese, with disrupted fasting/postprandial hormone profiles providing the hormonal basis for weight-dependent appetite dysfunction.","whyItMatters":"Relevant for neuropeptides, weight-loss, gut-healing.","specificNumbers":"","methodology":"cross-sectional study on neuropeptides, weight-loss.","limitations":"See abstract."},{"rthcId":"RPEP-01194","title":"Wheat-fibre-induced changes of postprandial peptide YY and ghrelin responses are not associated with acute alterations of satiety.","authors":"Weickert, Martin O; Spranger, Joachim; Holst, Jens J; Otto, Bärbel; Koebnick, Corinna; Möhlig, Matthias; Pfeiffer, Andreas F H","year":2006,"journal":"The British journal of nutrition, 96(5), 795-8","doi":null,"pmid":"17092365","tags":["neuropeptides","weight-loss","bioactive-food-peptides"],"studyType":"RCT","evidenceStrength":"moderate","keyFinding":"Wheat fiber modified postprandial PYY and ghrelin responses without immediate appetite changes, suggesting fiber-induced gut hormone modulation requires chronic exposure rather than acute meal effects for meaningful appetite impact.","whyItMatters":"Relevant for neuropeptides, weight-loss, bioactive-food-peptides.","specificNumbers":"","methodology":"RCT study on neuropeptides, weight-loss.","limitations":"See abstract."},{"rthcId":"RPEP-01195","title":"Arginine vasopressin enhances periaqueductal gray synthesis and secretion of enkephalin and endorphin in the rat.","authors":"Yang, Jun; Yang, Yu; Xu, Hong-Tao; Chen, Jian-Min; Liu, Wen-Yan; Lin, Bao-Chen","year":2006,"journal":"Brain research bulletin, 71(1-3), 193-9","doi":null,"pmid":"17113946","tags":["opioid-peptides","neuropeptides","pain"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Arginine vasopressin stimulated enkephalin and endorphin synthesis and secretion in the periaqueductal gray, demonstrating vasopressin-opioid peptide cross-talk in the brain's primary descending pain modulation center.","whyItMatters":"Relevant for opioid-peptides, neuropeptides, pain.","specificNumbers":"","methodology":"in-vitro study on opioid-peptides, neuropeptides.","limitations":"See abstract."},{"rthcId":"RPEP-01196","title":"Only arginine vasopressin, not oxytocin and endogenous opiate peptides, in hypothalamic paraventricular nucleus play a role in acupuncture analgesia in the rat.","authors":"Yang, Jun; Liu, Wen-yan; Song, Cao-you; Lin, Bao-cheng","year":2006,"journal":"Brain research bulletin, 68(6), 453-8","doi":null,"pmid":"16459202","tags":["oxytocin","opioid-peptides","neuropeptides","pain"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Only arginine vasopressin (not oxytocin or endogenous opioid peptides) in the paraventricular nucleus mediated electroacupuncture-induced analgesia — demonstrating pathway specificity where different brain nuclei use different peptide systems for the same analgesic effect.","whyItMatters":"Relevant for oxytocin, opioid-peptides, neuropeptides, pain.","specificNumbers":"","methodology":"animal-study study on oxytocin, opioid-peptides.","limitations":"See abstract."},{"rthcId":"RPEP-01197","title":"Through central arginine vasopressin, not oxytocin and endogenous opiate peptides, glutamate sodium induces hypothalamic paraventricular nucleus enhancing acupuncture analgesia in the rat.","authors":"Yang, Jun; Liu, Wen-Yan; Song, Cao-You; Lin, Bao-Cheng","year":2006,"journal":"Neuroscience research, 54(1), 49-56","doi":null,"pmid":"16310878","tags":["oxytocin","opioid-peptides","neuropeptides","pain"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"MSG-induced hypothalamic analgesia was mediated through central AVP signaling exclusively, with oxytocin and opioid peptide antagonists having no effect — confirming vasopressin's dominance in hypothalamic pain modulation pathways.","whyItMatters":"Relevant for oxytocin, opioid-peptides, neuropeptides, pain.","specificNumbers":"","methodology":"animal-study study on oxytocin, opioid-peptides.","limitations":"See abstract."},{"rthcId":"RPEP-01198","title":"Regulative effects of ovarian steroids on rat gastric motility and sensitivity.","authors":"Yang, Xia; Liu, Ran; Dong, Yan","year":2006,"journal":"Sheng li xue bao : [Acta physiologica Sinica], 58(3), 275-80","doi":null,"pmid":"16786113","tags":["neuropeptides","gut-healing"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Ovarian steroids (estrogen, progesterone) regulated gastric motility patterns and visceral sensitivity in rats, providing the hormonal mechanism for menstrual cycle-related GI symptom variations experienced by many women.","whyItMatters":"Relevant for neuropeptides, gut-healing.","specificNumbers":"","methodology":"animal-study study on neuropeptides, gut-healing.","limitations":"See abstract."},{"rthcId":"RPEP-01199","title":"Plasma neuropeptide Y concentrations in combat exposed veterans: relationship to trauma exposure, recovery from PTSD, and coping.","authors":"Yehuda, Rachel; Brand, Sarah; Yang, Ren-Kui","year":2006,"journal":"Biological psychiatry, 59(7), 660-3","doi":null,"pmid":"16325152","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01200","title":"Expression and bioactivity of recombinant human lysozyme in the milk of transgenic mice.","authors":"Yu, Z; Meng, Q; Yu, H; Fan, B; Yu, S; Fei, J; Wang, L; Dai, Y; Li, N","year":2006,"journal":"Journal of dairy science, 89(8), 2911-8","doi":null,"pmid":"16840606","tags":["antimicrobial-peptides","peptide-design"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Recombinant human lysozyme produced in transgenic mouse milk maintained bactericidal activity equivalent to native human lysozyme, validating mammary gland expression as a scalable production platform for bioactive antimicrobial milk proteins.","whyItMatters":"Relevant for antimicrobial-peptides, peptide-design.","specificNumbers":"","methodology":"animal-study study on antimicrobial-peptides, peptide-design.","limitations":"See abstract."},{"rthcId":"RPEP-01201","title":"Evolution of the primate cathelicidin. Correlation between structural variations and antimicrobial activity.","authors":"Zelezetsky, Igor; Pontillo, Alessandra; Puzzi, Luca; Antcheva, Nikolinka; Segat, Ludovica; Pacor, Sabrina; Crovella, Sergio; Tossi, Alessandro","year":2006,"journal":"The Journal of biological chemistry, 281(29), 19861-71","doi":null,"pmid":"16720578","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01202","title":"Quantitative PET imaging of tumor integrin alphavbeta3 expression with 18F-FRGD2.","authors":"Zhang, Xianzhong; Xiong, Zhengming; Wu, Yun; Cai, Weibo; Tseng, Jeffery R; Gambhir, Sanjiv S; Chen, Xiaoyuan","year":2006,"journal":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 47(1), 113-21","doi":null,"pmid":"16391195","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01203","title":"Modulation of cardiovascular excitatory responses in rats by transcutaneous magnetic stimulation: role of the spinal cord.","authors":"Zhou Yi Syuu, Wei; Hsiao, Ian; Lin, Vernon W H; Longhurst, John C","year":2006,"journal":"Journal of applied physiology (Bethesda, Md. : 1985), 100(3), 926-32","doi":null,"pmid":"16269522","tags":["neuropeptides","cardiovascular"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Transcutaneous magnetic stimulation modulated cardiovascular excitatory responses through spinal cord mechanisms involving opioid peptide and nociceptin pathways — establishing a non-invasive approach to modulating cardiovascular autonomic reflexes.","whyItMatters":"Relevant for neuropeptides, cardiovascular.","specificNumbers":"","methodology":"animal-study study on neuropeptides, cardiovascular.","limitations":"See abstract."},{"rthcId":"RPEP-01204","title":"The role of urotensin II in cardiovascular and renal physiology and diseases.","authors":"Zhu, Yi-Chun; Zhu, Yi-Zhun; Moore, Philip Keith","year":2006,"journal":"British journal of pharmacology, 148(7), 884-901","doi":null,"pmid":"16783414","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01205","title":"Influence of N-acylation of a peptide derived from human lactoferricin on membrane selectivity.","authors":"Zweytick, Dagmar; Pabst, Georg; Abuja, Peter M; Jilek, Alexander; Blondelle, Sylvie E; Andrä, Jörg; Jerala, Roman; Monreal, Daniel; Martinez de Tejada, Guillermo; Lohner, Karl","year":2006,"journal":"Biochimica et biophysica acta, 1758(9), 1426-35","doi":null,"pmid":"16616888","tags":["antimicrobial-peptides","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"N-acylation of a human lactoferricin-derived peptide improved membrane selectivity: maintaining or enhancing antibacterial activity while reducing toxicity to human cells — demonstrating lipid modification as a strategy for improving antimicrobial peptide therapeutic windows.","whyItMatters":"Relevant for antimicrobial-peptides, peptide-design.","specificNumbers":"","methodology":"in-vitro study on antimicrobial-peptides, peptide-design.","limitations":"See abstract."},{"rthcId":"RPEP-01206","title":"Natriuretic peptide biomarkers as information indicators in elderly patients with possible heart failure followed over six years: a head-to-head comparison of four cardiac natriuretic peptides.","authors":"Alehagen, Urban; Svensson, Erland; Dahlström, Ulf","year":2007,"journal":"Journal of cardiac failure, 13(6), 452-61","doi":null,"pmid":"17675059","tags":["natriuretic-peptides","cardiovascular"],"studyType":"cohort","evidenceStrength":"strong","keyFinding":"Serial NT-proBNP and BNP measurements over 6 months improved identification of elderly patients with progressive heart failure compared to single baseline measurements, with peptide trajectory providing superior diagnostic and prognostic information.","whyItMatters":"Relevant for natriuretic-peptides, cardiovascular.","specificNumbers":"","methodology":"cohort study on natriuretic-peptides, cardiovascular.","limitations":"See abstract."},{"rthcId":"RPEP-01207","title":"ABT-510, a modified type 1 repeat peptide of thrombospondin, inhibits malignant glioma growth in vivo by inhibiting angiogenesis.","authors":"Anderson, Joshua C; Grammer, J Robert; Wang, Wenquan; Nabors, L Burton; Henkin, Jack; Stewart, Jerry E; Gladson, Candece L","year":2007,"journal":"Cancer biology & therapy, 6(3), 454-62","doi":null,"pmid":"17384534","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01208","title":"Role of phosphatidylinositol-3 kinase-gamma in the actions of glucagon-like peptide-2 on the murine small intestine.","authors":"Anini, Younes; Izzo, Angelo; Oudit, Gavin Y; Backx, Peter H; Brubaker, Patricia L","year":2007,"journal":"American journal of physiology. Endocrinology and metabolism, 292(6), E1599-606","doi":null,"pmid":"17284578","tags":["glp-1","gut-healing"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"PI3K-gamma was identified as an essential mediator of GLP-2's intestinal mucosal growth effects, with PI3K-gamma knockout mice showing impaired GLP-2-stimulated mucosal proliferation — mapping the signal transduction for gut peptide-driven intestinal repair.","whyItMatters":"Relevant for glp-1, gut-healing.","specificNumbers":"","methodology":"animal-study study on glp-1, gut-healing.","limitations":"See abstract."},{"rthcId":"RPEP-01209","title":"The renin-angiotensin aldosterone system: pathophysiological role and pharmacologic inhibition.","authors":"Atlas, Steven A","year":2007,"journal":"Journal of managed care pharmacy : JMCP, 13(8 Suppl B), 9-20","doi":"10.18553/jmcp.2007.13.s8-b.9","pmid":"17970613","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01210","title":"Biology of incretins: GLP-1 and GIP.","authors":"Baggio, Laurie L; Drucker, Daniel J","year":2007,"journal":"Gastroenterology, 132(6), 2131-57","doi":null,"pmid":"17498508","tags":["glp-1","gip","incretin"],"studyType":"review","evidenceStrength":"high","keyFinding":"GLP-1 and GIP are both released within minutes of eating and help the body process nutrients by stimulating insulin release from pancreatic beta cells. Both peptides promote beta-cell growth and protect these cells from dying.\n\nHowever, the two peptides differ in important ways. GIP promotes fat storage and strengthens bones by stimulating bone-building cells. GLP-1, on the other hand, slows stomach emptying, suppresses glucagon (a sugar-raising hormone), promotes feelings of fullness, and is associated with weight loss.\n\nBoth peptides are rapidly broken down by the enzyme DPP-4, which led to two classes of diabetes drugs: degradation-resistant GLP-1 receptor agonists and DPP-4 inhibitors. These therapies lower HbA1c without causing weight gain in people with type 2 diabetes.","whyItMatters":"This review laid out the scientific foundation for the entire incretin-based drug class that would go on to become the most important development in diabetes and obesity treatment. Understanding how GLP-1 and GIP work differently — and how they complement each other — is essential to grasping why newer dual-agonist drugs like tirzepatide target both pathways simultaneously.","specificNumbers":"Both incretins secreted within minutes of eating · DPP-4 rapidly degrades both GLP-1 and GIP · GLP-1 agonists and DPP-4 inhibitors lower HbA1c without weight gain","methodology":"Comprehensive narrative review of the published scientific literature on GLP-1 and GIP biology, with emphasis on recent advances in understanding incretin synthesis, secretion, biological actions, receptor signaling, and therapeutic applications.","limitations":"As a narrative review from 2007, it predates the clinical success of semaglutide, tirzepatide, and other modern incretin therapies. It cannot account for the large-scale cardiovascular and weight-loss outcomes data that emerged in subsequent years. The review also could not anticipate the resurgence of interest in GIP receptor agonism as a therapeutic strategy."},{"rthcId":"RPEP-01211","title":"Thymosin alpha1 activates the TLR9/MyD88/IRF7-dependent murine cytomegalovirus sensing for induction of anti-viral responses in vivo.","authors":"Bozza, Silvia; Gaziano, Roberta; Bonifazi, Pierluigi; Zelante, Teresa; Pitzurra, Lucia; Montagnoli, Claudia; Moretti, Silvia; Castronari, Roberto; Sinibaldi, Paola; Rasi, Guido; Garaci, Enrico; Bistoni, Francesco; Romani, Luigina","year":2007,"journal":"International immunology, 19(11), 1261-70","doi":null,"pmid":"17804687","tags":["thymosin-alpha-1","immune-function","infection"],"studyType":"animal-study","evidenceStrength":"strong","keyFinding":"Thymosin alpha-1 activated the TLR9/MyD88/IRF7 pathway in dendritic cells, inducing type I interferon production for anti-murine cytomegalovirus defense — identifying the specific innate immune sensing pathway mediating thymosin alpha-1's antiviral activity.","whyItMatters":"Relevant for thymosin-alpha-1, immune-function, infection.","specificNumbers":"","methodology":"animal-study study on thymosin-alpha-1, immune-function.","limitations":"See abstract."},{"rthcId":"RPEP-01212","title":"Production of lactoferricin and other cationic peptides from food grade bovine lactoferrin with various iron saturation levels.","authors":"Chan, Judy C K; Li-Chan, Eunice C Y","year":2007,"journal":"Journal of agricultural and food chemistry, 55(2), 493-501","doi":null,"pmid":"17227084","tags":["antimicrobial-peptides","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Iron saturation of bovine lactoferrin significantly affected pepsin-generated lactoferricin yield and cationic peptide composition, with lower iron saturation producing more antimicrobial peptide — practical optimization for food-grade production.","whyItMatters":"Relevant for antimicrobial-peptides, peptide-design.","specificNumbers":"","methodology":"in-vitro study on antimicrobial-peptides, peptide-design.","limitations":"See abstract."},{"rthcId":"RPEP-01213","title":"Cholecystokinin.","authors":"Chandra, Rashmi; Liddle, Rodger A","year":2007,"journal":"Current opinion in endocrinology, diabetes, and obesity, 14(1), 63-7","doi":null,"pmid":"17940422","tags":["neuropeptides","weight-loss","gut-healing"],"studyType":"review","evidenceStrength":"strong","keyFinding":"CCK operates as both the primary gut satiety signal (reducing meal size through vagal afferent and brain CCK-A receptors) and a digestive coordinator (gallbladder contraction, pancreatic secretion) — the most comprehensively characterized gut hormone.","whyItMatters":"Relevant for neuropeptides, weight-loss, gut-healing.","specificNumbers":"","methodology":"review study on neuropeptides, weight-loss.","limitations":"See abstract."},{"rthcId":"RPEP-01214","title":"Nociceptin/orphanin FQ blocks the antinociception induced by mu, kappa and delta opioid agonists on the cold water tail-flick test.","authors":"Chen, Xiaohong; Geller, Ellen B; Adler, Martin W","year":2007,"journal":"European journal of pharmacology, 557(1), 32-6","doi":null,"pmid":"17173891","tags":["opioid-peptides","neuropeptides","pain"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Nociceptin/OFQ blocked spinal antinociception from mu (DAMGO), kappa (U50,488H), and delta (DPDPE) opioid agonists in the cold water tail-flick test, confirming nociceptin as a universal anti-opioid peptide opposing all three opioid receptor systems.","whyItMatters":"Relevant for opioid-peptides, neuropeptides, pain.","specificNumbers":"","methodology":"animal-study study on opioid-peptides, neuropeptides.","limitations":"See abstract."},{"rthcId":"RPEP-01215","title":"Dynorphin peptides differentially regulate the human kappa opioid receptor.","authors":"Chen, Yong; Chen, Chongguang; Liu-Chen, Lee-Yuan","year":2007,"journal":"Life sciences, 80(15), 1439-48","doi":null,"pmid":"17316701","tags":["opioid-peptides","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Different prodynorphin-derived peptides (dynorphin A, dynorphin B, alpha-neoendorphin) showed differential kappa receptor regulation: distinct patterns of internalization, signaling efficacy, and receptor recycling — demonstrating biased agonism from endogenous ligands.","whyItMatters":"Relevant for opioid-peptides, receptor-signaling.","specificNumbers":"","methodology":"in-vitro study on opioid-peptides, receptor-signaling.","limitations":"See abstract."},{"rthcId":"RPEP-01216","title":"Potent mitochondria-targeted peptides reduce myocardial infarction in rats.","authors":"Cho, Janghyun; Won, Kyungheon; Wu, DunLi; Soong, Yi; Liu, Shaoyi; Szeto, Hazel H; Hong, Mun K","year":2007,"journal":"Coronary artery disease, 18(3), 215-20","doi":null,"pmid":"17429296","tags":["opioid-peptides","cardiovascular","neuroprotection"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Mitochondria-targeted peptides (SS-31 and analogs) reduced myocardial infarct size by up to 60% in rat ischemia-reperfusion, with efficacy when given before ischemia or at reperfusion — demonstrating potent cardioprotection through preservation of mitochondrial function.","whyItMatters":"Relevant for opioid-peptides, cardiovascular, neuroprotection.","specificNumbers":"","methodology":"animal-study study on opioid-peptides, cardiovascular.","limitations":"See abstract."},{"rthcId":"RPEP-01217","title":"The chemistry and biology of cyclotides.","authors":"Craik, David J; Cemazar, Masa; Daly, Norelle L","year":2007,"journal":"Current opinion in drug discovery & development, 10(2), 176-84","doi":null,"pmid":"17436553","tags":["cyclic-peptides","peptide-design","antimicrobial-peptides"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Updated cyclotide review covering chemical synthesis, structure determination, grafting methodology, and expanding biological activities (antimicrobial, anticancer, insecticidal, anti-HIV, uterotonic) — advancing from natural products to engineered drug scaffolds.","whyItMatters":"Relevant for cyclic-peptides, peptide-design, antimicrobial-peptides.","specificNumbers":"","methodology":"review study on cyclic-peptides, peptide-design.","limitations":"See abstract."},{"rthcId":"RPEP-01218","title":"Ghrelin and its unacylated isoform stimulate the growth of adrenocortical tumor cells via an anti-apoptotic pathway.","authors":"Delhanty, P J D; van Koetsveld, P M; Gauna, C; van de Zande, B; Vitale, G; Hofland, L J; van der Lely, A J","year":2007,"journal":"American journal of physiology. Endocrinology and metabolism, 293(1), E302-9","doi":null,"pmid":"17405826","tags":["ghrp","cancer","hormone-optimization"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Both ghrelin and des-acyl ghrelin stimulated adrenocortical tumor cell proliferation via anti-apoptotic pathway activation (reduced caspase-3, increased Bcl-2), demonstrating pro-tumorigenic ghrelin system activity in adrenal cancer regardless of GHS-R1a-dependent signaling.","whyItMatters":"Relevant for ghrp, cancer, hormone-optimization.","specificNumbers":"","methodology":"in-vitro study on ghrp, cancer.","limitations":"See abstract."},{"rthcId":"RPEP-01219","title":"Synthesis and pharmacological in vitro and in vivo evaluations of novel triazole derivatives as ligands of the ghrelin receptor. 1.","authors":"Demange, Luc; Boeglin, Damien; Moulin, Aline; Mousseaux, Delphine; Ryan, Joanne; Bergé, Gilbert; Gagne, Didier; Heitz, Annie; Perrissoud, Daniel; Locatelli, Vittorio; Torsello, Antonio; Galleyrand, Jean-Claude; Fehrentz, Jean-Alain; Martinez, Jean","year":2007,"journal":"Journal of medicinal chemistry, 50(8), 1939-57","doi":null,"pmid":"17375904","tags":["ghrp","peptide-design","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Novel triazole derivatives showed nanomolar GHS-R1a binding and functional agonist activity in vitro and GH release in vivo, expanding the structural diversity of non-peptide ghrelin receptor ligands for drug development.","whyItMatters":"Relevant for ghrp, peptide-design, receptor-signaling.","specificNumbers":"","methodology":"in-vitro study on ghrp, peptide-design.","limitations":"See abstract."},{"rthcId":"RPEP-01220","title":"Prolonged esophagitis after primary dysfunction of the pyloric sphincter in the rat and therapeutic potential of the gastric pentadecapeptide BPC 157.","authors":"Dobric, Ivan; Drvis, Petar; Petrovic, Igor; Shejbal, Drazen; Brcic, Luka; Blagaic, Alenka Boban; Batelja, Lovorka; Sever, Marko; Kokic, Neven; Tonkic, Ante; Zoricic, Ivan; Mise, Sandro; Staresinic, Mario; Radic, Bozo; Jakir, Ana; Babel, Jaksa; Ilic, Spomenko; Vuksic, Tihomir; Jelic, Ivan; Anic, Tomislav; Seiwerth, Sven; Sikiric, Predrag","year":2007,"journal":"Journal of pharmacological sciences, 104(1), 7-18","doi":null,"pmid":"17452811","tags":["bpc-157","gut-healing"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"BPC-157 healed prolonged esophagitis caused by primary pyloric sphincter dysfunction in rats, improving mucosal integrity and sphincter function — demonstrating efficacy in a reflux model where the underlying cause is sphincter failure.","whyItMatters":"Relevant for bpc-157, gut-healing.","specificNumbers":"","methodology":"animal-study study on bpc-157, gut-healing.","limitations":"See abstract."},{"rthcId":"RPEP-01221","title":"Oxytocin improves \"mind-reading\" in humans.","authors":"Domes, Gregor; Heinrichs, Markus; Michel, Andre; Berger, Christoph; Herpertz, Sabine C","year":2007,"journal":"Biological psychiatry, 61(6), 731-3","doi":null,"pmid":"17137561","tags":["oxytocin","cognitive-enhancement","neuropeptides"],"studyType":"RCT","evidenceStrength":"moderate","keyFinding":"Intranasal oxytocin significantly improved performance on the Reading the Mind in the Eyes test in healthy men, demonstrating enhanced social cognition and emotional theory of mind — a distinct cognitive effect beyond anxiety reduction.","whyItMatters":"Relevant for oxytocin, cognitive-enhancement, neuropeptides.","specificNumbers":"","methodology":"RCT study on oxytocin, cognitive-enhancement.","limitations":"See abstract."},{"rthcId":"RPEP-01222","title":"C-Peptide replacement therapy and sensory nerve function in type 1 diabetic neuropathy.","authors":"Ekberg, Karin; Brismar, Tom; Johansson, Bo-Lennart; Lindström, Per; Juntti-Berggren, Lisa; Norrby, Anders; Berne, Christian; Arnqvist, Hans J; Bolinder, Jan; Wahren, John","year":2007,"journal":"Diabetes care, 30(1), 71-6","doi":null,"pmid":"17192336","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"C-peptide replacement therapy for 6 months improved sensory nerve conduction velocity (SCV) in type 1 diabetic patients with neuropathy. Both dose groups (1.5 mg/day and 4.5 mg/day) showed similar improvement. In the less severely affected patients (SCV < 2.5 SD below normal at baseline, n=70), SCV improved by 1.0 m/s compared to placebo (p<0.014). The proportion of patients showing SCV improvement >1.0 m/s was significantly greater in C-peptide groups versus placebo (p<0.03). Clinical neurological impairment scores and vibration perception also improved (p<0.011 and p<0.002 respectively). These improvements occurred independently of blood sugar control, which changed similarly across all groups.","whyItMatters":"Diabetic neuropathy is the most common complication of type 1 diabetes, causing numbness, pain, and loss of sensation in the extremities, with no approved disease-modifying treatment. C-peptide — a natural byproduct of insulin production that is completely absent in type 1 diabetes — showed the ability to actually improve nerve function, not just slow deterioration. This is the first randomized controlled trial showing that replacing a missing peptide can reverse neuropathy damage.","specificNumbers":"n=139 completed · 6-month treatment · 1.5 or 4.5 mg/day SC · SCV improved 1.0 m/s vs. placebo (p<0.014 in less severe) · NIA score improved (p<0.011) · Vibration perception improved (p<0.002) · 86% had clinical neuropathy at baseline · Mean diabetes duration 30.6 years","methodology":"Exploratory, double-blinded, randomized, placebo-controlled trial at five centers in Sweden. 139 type 1 diabetes patients with peripheral neuropathy completed the protocol. Three groups: C-peptide 1.5 mg/day (replacement dose, four subcutaneous injections daily), C-peptide 4.5 mg/day (3× replacement), or placebo. Neurological examination and neurophysiological measurements (nerve conduction velocity, vibration perception, clinical impairment scores) were performed at baseline and 6 months.","limitations":"Described as 'exploratory,' suggesting it was powered for signal detection rather than definitive efficacy. The four-times-daily injection regimen is burdensome. The higher dose (4.5 mg/day) didn't show greater benefit than the replacement dose, raising questions about the dose-response relationship. Six months may be too short to see full nerve regeneration effects. The study was published in 2007, and C-peptide has not progressed to approval despite these promising results."},{"rthcId":"RPEP-01223","title":"Role of capsaicin-sensitive afferents and sensory neuropeptides in endotoxin-induced airway inflammation and consequent bronchial hyperreactivity in the mouse.","authors":"Elekes, Krisztián; Helyes, Zsuzsanna; Németh, József; Sándor, Katalin; Pozsgai, Gábor; Kereskai, László; Börzsei, Rita; Pintér, Erika; Szabó, Arpád; Szolcsányi, János","year":2007,"journal":"Regulatory peptides, 141(1-3), 44-54","doi":null,"pmid":"17291600","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01224","title":"Thymosin alpha 1 as an adjunct to influenza vaccination in the elderly: rationale and trial summaries.","authors":"Ershler, William B; Gravenstein, Stefan; Geloo, Zeba S","year":2007,"journal":"Annals of the New York Academy of Sciences, 1112, 375-84","doi":null,"pmid":"17600281","tags":["thymosin-alpha-1","immune-function","anti-aging"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Thymosin alpha-1 as an influenza vaccine adjuvant improved seroconversion and antibody titers in elderly adults with normally impaired vaccine responses, addressing the immunosenescence that makes influenza vaccination less effective in the aged.","whyItMatters":"Relevant for thymosin-alpha-1, immune-function, anti-aging.","specificNumbers":"","methodology":"review study on thymosin-alpha-1, immune-function.","limitations":"See abstract."},{"rthcId":"RPEP-01225","title":"Organization of endogenous opioids in the rostral agranular insular cortex of the rat.","authors":"Evans, Joshua M; Bey, Vincent; Burkey, Adam R; Commons, Kathryn G","year":2007,"journal":"The Journal of comparative neurology, 500(3), 530-41","doi":null,"pmid":"17120290","tags":["opioid-peptides","neuropeptides","pain"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Immunohistochemical mapping revealed distinct laminar distributions of met-enkephalin, dynorphin, and beta-endorphin in the rostral agranular insular cortex — the brain's emotional pain processing region — providing the opioid peptide architecture for pain affect modulation.","whyItMatters":"Relevant for opioid-peptides, neuropeptides, pain.","specificNumbers":"","methodology":"animal-study study on opioid-peptides, neuropeptides.","limitations":"See abstract."},{"rthcId":"RPEP-01226","title":"Metabolic effects of a growth hormone-releasing factor in patients with HIV.","authors":"Falutz, Julian; Allas, Soraya; Blot, Koenraad; Potvin, Diane; Kotler, Donald; Somero, Michael; Berger, Daniel; Brown, Stephen; Richmond, Gary; Fessel, Jeffrey; Turner, Ralph; Grinspoon, Steven","year":2007,"journal":"The New England journal of medicine, 357(23), 2359-70","doi":null,"pmid":"18057338","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01227","title":"Insights into a role of GH secretagogues in reversing the age-related decline in the GH/IGF-I axis.","authors":"Frutos, Miriam García-San; Cacicedo, Lucinda; Fernández, Carolina; Vicent, David; Velasco, Beatriz; Zapatero, Helena; Sánchez-Franco, Franco","year":2007,"journal":"American journal of physiology. Endocrinology and metabolism, 293(5), E1140-52","doi":null,"pmid":"17684105","tags":["ghrp","hormone-optimization","anti-aging"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"GH secretagogues reversed age-related GH/IGF-I axis decline in aged rats by restoring hypothalamic GHRH sensitivity and pituitary responsiveness, with combined GHRP + GHRH achieving the most complete axis restoration for anti-aging neuroendocrine therapy.","whyItMatters":"Relevant for ghrp, hormone-optimization, anti-aging.","specificNumbers":"","methodology":"animal-study study on ghrp, hormone-optimization.","limitations":"See abstract."},{"rthcId":"RPEP-01228","title":"Tumor targeting with RGD peptide ligands-design of new molecular conjugates for imaging and therapy of cancers.","authors":"Garanger, Elisabeth; Boturyn, Didier; Dumy, Pascal","year":2007,"journal":"Anti-cancer agents in medicinal chemistry, 7(5), 552-8","doi":null,"pmid":"17896915","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01229","title":"Unacylated ghrelin is not a functional antagonist but a full agonist of the type 1a growth hormone secretagogue receptor (GHS-R).","authors":"Gauna, Carlotta; van de Zande, Bedette; van Kerkwijk, Anke; Themmen, Axel P N; van der Lely, A J; Delhanty, Patric J D","year":2007,"journal":"Molecular and cellular endocrinology, 274(1-2), 30-4","doi":null,"pmid":"17601657","tags":["ghrp","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Des-acyl ghrelin, previously considered inactive at GHS-R1a, demonstrated full agonist activity at the type 1a receptor — challenging the fundamental assumption that only acylated ghrelin has GHS-R activity and redefining des-acyl ghrelin's biological role.","whyItMatters":"Relevant for ghrp, receptor-signaling.","specificNumbers":"","methodology":"in-vitro study on ghrp, receptor-signaling.","limitations":"See abstract."},{"rthcId":"RPEP-01230","title":"Essential role of mu opioid receptor in the regulation of delta opioid receptor-mediated antihyperalgesia.","authors":"Gendron, L; Pintar, J E; Chavkin, C","year":2007,"journal":"Neuroscience, 150(4), 807-17","doi":null,"pmid":"17997230","tags":["opioid-peptides","pain","inflammation"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Mu-opioid receptor function was essential for delta-opioid receptor-mediated anti-hyperalgesia in inflammatory pain, with mu blockade eliminating delta agonist efficacy — demonstrating mu-delta functional dependence and implications for selective opioid drug design.","whyItMatters":"Relevant for opioid-peptides, pain, inflammation.","specificNumbers":"","methodology":"animal-study study on opioid-peptides, pain.","limitations":"See abstract."},{"rthcId":"RPEP-01231","title":"Synthesis of bicyclic alkene-/alkane-bridged nisin mimics by ring-closing metathesis and their biochemical evaluation as lipid II binders: toward the design of potential novel antibiotics.","authors":"Ghalit, Nourdin; Reichwein, John F; Hilbers, Hans W; Breukink, Eefjan; Rijkers, Dirk T S; Liskamp, Rob M J","year":2007,"journal":"Chembiochem : a European journal of chemical biology, 8(13), 1540-54","doi":null,"pmid":"17674393","tags":["antimicrobial-peptides","peptide-design","infection"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Bicyclic nisin analogs synthesized via ring-closing metathesis retained antimicrobial activity against gram-positive bacteria, validating chemical synthesis approaches for producing and optimizing this clinically important natural cyclic peptide antibiotic.","whyItMatters":"Relevant for antimicrobial-peptides, peptide-design, infection.","specificNumbers":"","methodology":"in-vitro study on antimicrobial-peptides, peptide-design.","limitations":"See abstract."},{"rthcId":"RPEP-01232","title":"Receptor activity-modifying proteins: RAMPing up adrenomedullin signaling.","authors":"Gibbons, Carrie; Dackor, Ryan; Dunworth, William; Fritz-Six, Kimberly; Caron, Kathleen M","year":2007,"journal":"Molecular endocrinology (Baltimore, Md.), 21(4), 783-96","doi":null,"pmid":"17053041","tags":["neuropeptides","receptor-signaling","cardiovascular"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"RAMPs regulate adrenomedullin signaling by modifying calcitonin receptor-like receptor (CLR) specificity: RAMP2/RAMP3 create AM receptors, RAMP1 creates CGRP receptor — explaining how one receptor serves multiple peptide ligands through RAMP partnerships.","whyItMatters":"Relevant for neuropeptides, receptor-signaling, cardiovascular.","specificNumbers":"","methodology":"review study on neuropeptides, receptor-signaling.","limitations":"See abstract."},{"rthcId":"RPEP-01233","title":"Emerging roles of vasoactive intestinal peptide: a new approach for autoimmune therapy.","authors":"Gonzalez-Rey, Elena; Anderson, Per; Delgado, Mario","year":2007,"journal":"Annals of the rheumatic diseases, 66 Suppl 3(Suppl 3), iii70-6","doi":null,"pmid":"17934101","tags":["neuropeptides","inflammation","immune-function"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"VIP generates regulatory T-cells, tolerizes dendritic cells, and suppresses Th1/Th17 inflammatory pathways, providing a comprehensive anti-autoimmune mechanism applicable to rheumatoid arthritis, MS, type 1 diabetes, and transplant rejection.","whyItMatters":"Relevant for neuropeptides, inflammation, immune-function.","specificNumbers":"","methodology":"review study on neuropeptides, inflammation.","limitations":"See abstract."},{"rthcId":"RPEP-01234","title":"New therapies for diabetes.","authors":"Green, Dina E","year":2007,"journal":"Clinical cornerstone, 8(2), 58-63; discussion 64-5","doi":null,"pmid":"18357956","tags":["glp-1","diabetes"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"GLP-1 receptor agonists and DPP-4 inhibitors exploit the incretin system for diabetes treatment, providing glucose-dependent insulin stimulation, weight loss (GLP-1 agonists), and low hypoglycemia risk — the most significant new diabetes drug class.","whyItMatters":"Relevant for glp-1, diabetes.","specificNumbers":"","methodology":"review study on glp-1, diabetes.","limitations":"See abstract."},{"rthcId":"RPEP-01235","title":"The cyclic cystine knot miniprotein MCoTI-II is internalized into cells by macropinocytosis.","authors":"Greenwood, Kathryn P; Daly, Norelle L; Brown, Darren L; Stow, Jennifer L; Craik, David J","year":2007,"journal":"The international journal of biochemistry & cell biology, 39(12), 2252-64","doi":null,"pmid":"17693122","tags":["cyclic-peptides","peptide-delivery","cell-penetrating"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"MCoTI-II was internalized into human cells through macropinocytosis (not receptor-mediated endocytosis), accumulating in cytoplasm — demonstrating that macrocyclic peptide scaffolds can access intracellular targets, dramatically expanding their drug design utility.","whyItMatters":"Relevant for cyclic-peptides, peptide-delivery, cell-penetrating.","specificNumbers":"","methodology":"in-vitro study on cyclic-peptides, peptide-delivery.","limitations":"See abstract."},{"rthcId":"RPEP-01236","title":"The role of peptide YY in integrative gut physiology and potential role in obesity.","authors":"Grudell, April B M; Camilleri, Michael","year":2007,"journal":"Current opinion in endocrinology, diabetes, and obesity, 14(1), 52-7","doi":null,"pmid":"17940420","tags":["neuropeptides","weight-loss"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"PYY integrates multiple gut functions: suppresses appetite (Y2R-mediated), slows gastric emptying, reduces intestinal motility, decreases pancreatic secretion, and promotes fluid absorption — PYY deficiency in obesity contributes to the disordered satiety driving overeating.","whyItMatters":"Relevant for neuropeptides, weight-loss.","specificNumbers":"","methodology":"review study on neuropeptides, weight-loss.","limitations":"See abstract."},{"rthcId":"RPEP-01237","title":"Ethanol-induced effects on opioid peptides in adult male Wistar rats are dependent on early environmental factors.","authors":"Gustafsson, L; Zhou, Q; Nylander, I","year":2007,"journal":"Neuroscience, 146(3), 1137-49","doi":null,"pmid":"17391858","tags":["opioid-peptides","addiction","neuropeptides"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Ethanol-induced changes in brain opioid peptides (dynorphin, enkephalin) in adult Wistar rats were modulated by early postnatal environment (maternal separation), demonstrating gene × early environment interaction programming adult opioid system alcohol sensitivity.","whyItMatters":"Relevant for opioid-peptides, addiction, neuropeptides.","specificNumbers":"","methodology":"animal-study study on opioid-peptides, addiction.","limitations":"See abstract."},{"rthcId":"RPEP-01238","title":"beta-Thymosins.","authors":"Hannappel, E","year":2007,"journal":"Annals of the New York Academy of Sciences, 1112, 21-37","doi":null,"pmid":"17468232","tags":["thymosin-beta-4","immune-function","wound-healing"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Beta-thymosins (thymosin beta-4 predominantly) regulate actin polymerization and exhibit wound healing, anti-inflammatory, angiogenic, and cardioprotective activities — a structurally and functionally distinct peptide family from thymosin alpha-1 with unique therapeutic potential.","whyItMatters":"Relevant for thymosin-beta-4, immune-function, wound-healing.","specificNumbers":"","methodology":"review study on thymosin-beta-4, immune-function.","limitations":"See abstract."},{"rthcId":"RPEP-01239","title":"The medicinal chemistry of short lactoferricin-based antibacterial peptides.","authors":"Haug, B E; Strøm, M B; Svendsen, J S M","year":2007,"journal":"Current medicinal chemistry, 14(1), 1-18","doi":null,"pmid":"17266565","tags":["antimicrobial-peptides","peptide-design","infection"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Medicinal chemistry review of short lactoferricin-derived antibacterial peptides covering: minimal pharmacophore identification, selectivity optimization (bacteria vs human cells), proteolytic stability enhancement, and design rules for drug-like antimicrobial peptides.","whyItMatters":"Relevant for antimicrobial-peptides, peptide-design, infection.","specificNumbers":"","methodology":"review study on antimicrobial-peptides, peptide-design.","limitations":"See abstract."},{"rthcId":"RPEP-01240","title":"A carbohydrate-restricted diet alters gut peptides and adiposity signals in men and women with metabolic syndrome.","authors":"Hayes, Matthew R; Miller, Carla K; Ulbrecht, Jan S; Mauger, Joanna L; Parker-Klees, Lynn; Gutschall, Melissa Davis; Mitchell, Diane C; Smiciklas-Wright, Helen; Covasa, Mihai","year":2007,"journal":"The Journal of nutrition, 137(8), 1944-50","doi":null,"pmid":"17634268","tags":["neuropeptides","weight-loss","glp-1"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"Carbohydrate restriction in metabolic syndrome patients modified gut peptide profiles (reduced ghrelin, altered PYY) and adipokine levels (decreased leptin, increased adiponectin), with hormonal changes correlating with weight loss and improved metabolic markers.","whyItMatters":"Relevant for neuropeptides, weight-loss, glp-1.","specificNumbers":"","methodology":"clinical-trial study on neuropeptides, weight-loss.","limitations":"See abstract."},{"rthcId":"RPEP-01241","title":"Casein hydrolysate containing the antihypertensive tripeptides Val-Pro-Pro and Ile-Pro-Pro improves vascular endothelial function independent of blood pressure-lowering effects: contribution of the inhibitory action of angiotensin-converting enzyme.","authors":"Hirota, Tatsuhiko; Ohki, Kohji; Kawagishi, Rikako; Kajimoto, Yoshitaka; Mizuno, Seiichi; Nakamura, Yasunori; Kitakaze, Masafumi","year":2007,"journal":"Hypertension research : official journal of the Japanese Society of Hypertension, 30(6), 489-96","doi":null,"pmid":"17664851","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01242","title":"Cardiovascular and renal actions of melanocyte-stimulating hormone peptides.","authors":"Humphreys, Michael H","year":2007,"journal":"Current opinion in nephrology and hypertension, 16(1), 32-8","doi":null,"pmid":"17143069","tags":[],"studyType":"Review","evidenceStrength":"moderate","keyFinding":"Melanocyte-stimulating hormone peptides (melanocortins) play previously unrecognized roles in blood pressure regulation and sodium metabolism. Both alpha-MSH and gamma-MSH acutely raise blood pressure and heart rate by stimulating the sympathetic nervous system, but through different receptor mechanisms: alpha-MSH acts via the MC4R receptor, while gamma-MSH likely activates a central sodium channel rather than its MC3R receptor.\n\nParadoxically, gamma-MSH deficiency causes severe salt-sensitive hypertension — meaning too little of this peptide makes blood pressure dangerously responsive to salt intake. Delivering a small dose of gamma-MSH directly into the brain of deficient mice normalizes blood pressure. This salt-sensitive hypertension is also linked to the development of insulin resistance, though the connecting mechanism remains unknown and may involve sympathetic nervous system activation.","whyItMatters":"Salt-sensitive hypertension affects a large proportion of people with high blood pressure, and insulin resistance frequently accompanies it — but the link between the two has been poorly understood. This review reveals melanocortin peptides as a missing piece of the puzzle, connecting salt handling, blood pressure, sympathetic nervous activity, and metabolic dysfunction through a single peptide system. It also raises an important safety consideration for melanocortin drugs: their potential cardiovascular effects.","specificNumbers":"Alpha-MSH acts via MC4R · Gamma-MSH acts via sodium channel (not MC3R) · Gamma-MSH deficiency → salt-sensitive hypertension · Cerebroventricular gamma-MSH restores normal BP in deficient mice · Salt-sensitive hypertension linked to insulin resistance","methodology":"Narrative review published in Current Opinion in Nephrology and Hypertension, synthesizing recent findings on the cardiovascular and renal effects of melanocortin peptides from both animal models and mechanistic studies.","limitations":"Published in 2007, so more recent findings may have expanded on these observations. All cardiovascular and renal data discussed is from animal models — clinical translation to human hypertension has not been established. The mechanism linking salt-sensitive hypertension to insulin resistance via melanocortins was not yet determined at the time of publication."},{"rthcId":"RPEP-01243","title":"Inhibition of core histone acetylation by the cancer preventive peptide lunasin.","authors":"Jeong, Hyung Jin; Jeong, Jin Boo; Kim, Dae Seop; de Lumen, Ben O","year":2007,"journal":"Journal of agricultural and food chemistry, 55(3), 632-7","doi":null,"pmid":"17263453","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Lunasin from various Korean soybean varieties inhibited core histone H3 and H4 acetylation in a dose-dependent manner, with the degree of inhibition correlating to the amount of lunasin present. Both natural soy-derived lunasin and synthetic lunasin showed the same activity.\n\nCritically for practical relevance, lunasin in enriched soy survived in vitro pepsin digestion and was found intact in blood and liver tissue of rats fed lunasin-enriched soy (LES). The extracted lunasin retained its histone acetylation inhibitory activity, demonstrating oral bioavailability — a rare achievement for a dietary peptide of this size.","whyItMatters":"Most dietary peptides are destroyed during digestion, making them unlikely to have systemic effects. Lunasin is exceptional because it survives stomach acid and reaches the bloodstream intact. Its proposed mechanism — blocking histone acetylation to prevent cancer cell transformation — represents an epigenetic approach to cancer prevention that is fundamentally different from conventional antioxidant-based dietary cancer prevention theories.","specificNumbers":"","methodology":"Researchers extracted lunasin from multiple Korean soybean varieties and measured its presence by immunostaining. Histone acetylation inhibition was quantified using a non-radioactive histone acetyltransferase assay. Stability was tested through in vitro pepsin digestion. Bioavailability was assessed in rats fed lunasin-enriched soy, with lunasin extracted from blood and liver tissue and tested for intact structure and biological activity.","limitations":"This is a preclinical study with in vitro and rat data only — no human evidence exists for lunasin's cancer-preventive effects. The correlation between lunasin content and histone acetylation inhibition doesn't establish that eating soy prevents cancer. The rat bioavailability data doesn't specify what percentage of ingested lunasin reaches the bloodstream intact. The mechanistic model linking histone acetylation inhibition to cancer prevention, while plausible, has not been validated in long-term cancer outcome studies."},{"rthcId":"RPEP-01244","title":"The cancer preventive peptide lunasin from wheat inhibits core histone acetylation.","authors":"Jeong, Hyung Jin; Jeong, Jin Boo; Kim, Dae Seop; Park, Jae Ho; Lee, Jung Bok; Kweon, Dae-Hyuk; Chung, Gyu Young; Seo, Eul Won; de Lumen, Ben O","year":2007,"journal":"Cancer letters, 255(1), 42-8","doi":null,"pmid":"17481808","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Lunasin isolated from wheat seeds at different developmental stages inhibited core histone H3 and H4 acetylation in a dose-dependent manner. This is significant because histone acetylation is an epigenetic switch that can activate cancer-promoting genes.\n\nKey findings included:\n- Wheat was confirmed as a new dietary source of lunasin (previously found only in soy and barley)\n- The peptide's identity was confirmed by Western blot and LC-ESI-MS mass spectrometry\n- Lunasin extracted from livers of rats fed lunasin-enriched wheat also inhibited histone acetylation, confirming the peptide survives digestion intact and bioactive\n- The amount of lunasin correlated strongly with the degree of histone acetylation inhibition","whyItMatters":"Epigenetic changes — modifications to how genes are expressed without changing the DNA sequence — play a major role in cancer development. A naturally occurring food peptide that can block one of these cancer-promoting switches (histone acetylation) and survive digestion to reach internal organs is a compelling candidate for cancer chemoprevention through diet.","specificNumbers":"","methodology":"Researchers extracted lunasin from wheat seeds at different developmental stages and confirmed its identity using Western blot and liquid chromatography electrospray ionization mass spectrometry (LC-ESI-MS). They measured histone acetylation inhibition using a non-radioactive histone acetyltransferase assay. For the bioavailability component, male Sprague-Dawley rats were fed lunasin-enriched wheat, and lunasin was then extracted from their livers and tested for histone acetylation inhibitory activity.","limitations":"This is a preclinical study using cell-free assays and a rat feeding model. No human data on lunasin's cancer-preventive effects exists. The histone acetylation inhibition was measured in vitro and in rat liver extracts — it's unclear whether the same effect occurs in human cells at dietary concentrations. The correlation between lunasin amount and acetylation inhibition, while strong, doesn't prove cancer prevention in whole organisms."},{"rthcId":"RPEP-01245","title":"Low-dose pancreatic polypeptide inhibits food intake in man.","authors":"Jesudason, David R; Monteiro, Mariana P; McGowan, Barbara M C; Neary, Nicola M; Park, Adrian J; Philippou, Elena; Small, Caroline J; Frost, Gary S; Ghatei, Mohammad A; Bloom, Stephen R","year":2007,"journal":"The British journal of nutrition, 97(3), 426-9","doi":null,"pmid":"17313701","tags":[],"studyType":"rct","evidenceStrength":"moderate","keyFinding":"Intravenous infusion of pancreatic polypeptide (PP) at 5 pmol/kg per min — half the dose used in prior studies — reduced energy intake by 11% compared to saline in 14 lean volunteers (2440 vs. 2730 kJ; P<0.05). Preprandial hunger scores were also lower in the PP group. Notably, these appetite-suppressing effects were achieved at plasma PP levels within the pathophysiological range seen in patients with pancreatic tumors, rather than at the supraphysiological levels used previously.","whyItMatters":"This study demonstrated that even a low dose of pancreatic polypeptide can meaningfully reduce food intake in humans, strengthening the case that PP functions as a natural satiety signal. It suggested that PP-based therapies might offer a physiologically grounded approach to appetite control, relevant to the growing field of gut peptide-based weight management.","specificNumbers":"n=14 · 11% reduction in energy intake · PP 5 pmol/kg/min · 2440 vs 2730 kJ · P<0.05","methodology":"Randomized, double-blind, placebo-controlled crossover study in 14 lean fasted volunteers (5 men, 9 women). Participants received 90-minute IV infusions of either PP (5 pmol/kg per min) or saline on two separate days. One hour after infusion ended, a buffet lunch was served and energy intake measured. Hunger was assessed using visual analogue scales.","limitations":"Small sample size of only 14 participants. IV administration is not practical for real-world use. Only lean volunteers were studied — effects in overweight or obese individuals are unknown. Single-meal measurement does not capture longer-term appetite effects. Crossover design helps but the study was still underpowered."},{"rthcId":"RPEP-01246","title":"Immunoregulation of thymosin alpha 1 treatment of cytomegalovirus infection accompanied with acute respiratory distress syndrome after renal transplantation.","authors":"Ji, S-M; Li, L-S; Sun, Q-Q; Chen, J-S; Sha, G-Z; Liu, Z-H","year":2007,"journal":"Transplantation proceedings, 39(1), 115-9","doi":null,"pmid":"17275486","tags":["thymosin-alpha-1","infection","immune-function"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"Thymosin alpha-1 enhanced immune function (CD4+/CD8+ T-cells, NK cells) and improved clinical outcomes in patients with CMV infection complicated by ARDS, demonstrating clinical efficacy for severe opportunistic viral infections.","whyItMatters":"Relevant for thymosin-alpha-1, infection, immune-function.","specificNumbers":"","methodology":"clinical-trial study on thymosin-alpha-1, infection.","limitations":"See abstract."},{"rthcId":"RPEP-01247","title":"Plasma brain natriuretic peptide-guided therapy to improve outcome in heart failure: the STARS-BNP Multicenter Study.","authors":"Jourdain, Patrick; Jondeau, Guillaume; Funck, François; Gueffet, Pascal; Le Helloco, Alain; Donal, Erwan; Aupetit, Jean F; Aumont, Marie C; Galinier, Michel; Eicher, Jean C; Cohen-Solal, Alain; Juillière, Yves","year":2007,"journal":"Journal of the American College of Cardiology, 49(16), 1733-9","doi":null,"pmid":"17448376","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01248","title":"Annexin II expressed by osteoblasts and endothelial cells regulates stem cell adhesion, homing, and engraftment following transplantation.","authors":"Jung, Younghun; Wang, Jingcheng; Song, Junhui; Shiozawa, Yusuke; Wang, Jianhua; Havens, Aaron; Wang, Zhuo; Sun, Yan-Xi; Emerson, Stephen G; Krebsbach, Paul H; Taichman, Russell S","year":2007,"journal":"Blood, 110(1), 82-90","doi":null,"pmid":"17360942","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01249","title":"Polymorphism of bovine beta-casein and its potential effect on human health.","authors":"Kamiński, Stanisław; Cieslińska, Anna; Kostyra, Elzbieta","year":2007,"journal":"Journal of applied genetics, 48(3), 189-98","doi":null,"pmid":"17666771","tags":["opioid-peptides","bioactive-food-peptides"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"A1 beta-casein releases more beta-casomorphin-7 (BCM-7) during digestion than A2, with BCM-7 showing opioid, immunomodulatory, and GI effects that may explain the health differences attributed to A1 versus A2 milk consumption.","whyItMatters":"Relevant for opioid-peptides, bioactive-food-peptides.","specificNumbers":"","methodology":"review study on opioid-peptides, bioactive-food-peptides.","limitations":"See abstract."},{"rthcId":"RPEP-01250","title":"The role of leptin and ghrelin in the regulation of food intake and body weight in humans: a review.","authors":"Klok, M D; Jakobsdottir, S; Drent, M L","year":2007,"journal":"Obesity reviews : an official journal of the International Association for the Study of Obesity, 8(1), 21-34","doi":null,"pmid":"17212793","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01251","title":"Impaired heart contractility in Apelin gene-deficient mice associated with aging and pressure overload.","authors":"Kuba, Keiji; Zhang, Liyong; Imai, Yumiko; Arab, Sara; Chen, Manyin; Maekawa, Yuichiro; Leschnik, Michael; Leibbrandt, Andreas; Markovic, Mato; Schwaighofer, Julia; Beetz, Nadine; Musialek, Renata; Neely, G Greg; Komnenovic, Vukoslav; Kolm, Ursula; Metzler, Bernhard; Ricci, Romeo; Hara, Hiromitsu; Meixner, Arabella; Nghiem, Mai; Chen, Xin; Dawood, Fayez; Wong, Kit Man; Sarao, Renu; Cukerman, Eva; Kimura, Akinori; Hein, Lutz; Thalhammer, Johann; Liu, Peter P; Penninger, Josef M","year":2007,"journal":"Circulation research, 101(4), e32-42","doi":null,"pmid":"17673668","tags":["neuropeptides","cardiovascular"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Apelin knockout mice showed impaired cardiac contractility that worsened with aging and pressure overload, definitively establishing apelin as an essential cardiac peptide and a therapeutic target for heart failure and age-related cardiac decline.","whyItMatters":"Relevant for neuropeptides, cardiovascular.","specificNumbers":"","methodology":"animal-study study on neuropeptides, cardiovascular.","limitations":"See abstract."},{"rthcId":"RPEP-01252","title":"Antimicrobial peptides as new recognition molecules for screening challenging species.","authors":"Kulagina, Nadezhda V; Shaffer, Kara M; Ligler, Frances S; Taitt, Chris R","year":2007,"journal":"Sensors and actuators. B, Chemical, 121(1), 150-157","doi":null,"pmid":"18231571","tags":["antimicrobial-peptides","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Antimicrobial peptides were repurposed as bacterial recognition molecules for biosensor-based detection, exploiting their selective membrane-binding properties for rapid pathogen identification — a diagnostic application beyond antimicrobial therapy.","whyItMatters":"Relevant for antimicrobial-peptides, peptide-design.","specificNumbers":"","methodology":"in-vitro study on antimicrobial-peptides, peptide-design.","limitations":"See abstract."},{"rthcId":"RPEP-01253","title":"Antimicrobial peptide-lipid binding interactions and binding selectivity.","authors":"Lad, Mitaben D; Birembaut, Fabrice; Clifton, Luke A; Frazier, Richard A; Webster, John R P; Green, Rebecca J","year":2007,"journal":"Biophysical journal, 92(10), 3575-86","doi":null,"pmid":"17325007","tags":["antimicrobial-peptides","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Antimicrobial peptide selectivity for bacteria depends on preferential electrostatic binding to anionic bacterial membrane lipids (PG, CL) over zwitterionic human membrane lipids (PC, SM), with hydrophobic insertion depth determining killing efficiency — the molecular basis for therapeutic selectivity.","whyItMatters":"Relevant for antimicrobial-peptides, receptor-signaling.","specificNumbers":"","methodology":"in-vitro study on antimicrobial-peptides, receptor-signaling.","limitations":"See abstract."},{"rthcId":"RPEP-01254","title":"The galanin peptide family: receptor pharmacology, pleiotropic biological actions, and implications in health and disease.","authors":"Lang, Roland; Gundlach, Andrew L; Kofler, Barbara","year":2007,"journal":"Pharmacology & therapeutics, 115(2), 177-207","doi":null,"pmid":"17604107","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01255","title":"Gut hormones as mediators of appetite and weight loss after Roux-en-Y gastric bypass.","authors":"le Roux, Carel W; Welbourn, Richard; Werling, Malin; Osborne, Alan; Kokkinos, Alexander; Laurenius, Anna; Lönroth, Hans; Fändriks, Lars; Ghatei, Mohammad A; Bloom, Stephen R; Olbers, Torsten","year":2007,"journal":"Annals of surgery, 246(5), 780-5","doi":null,"pmid":"17968169","tags":["glp-1","neuropeptides","weight-loss"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"Enhanced GLP-1 and PYY responses with suppressed ghrelin after RYGB mediated sustained appetite reduction and weight loss, with gut hormone changes persisting years post-surgery — establishing hormonal modification (not just restriction) as the primary mechanism of bariatric success.","whyItMatters":"Relevant for glp-1, neuropeptides, weight-loss.","specificNumbers":"","methodology":"clinical-trial study on glp-1, neuropeptides.","limitations":"See abstract."},{"rthcId":"RPEP-01256","title":"Vasoactive intestinal peptide regulates Th17 function in autoimmune inflammation.","authors":"Leceta, Javier; Gomariz, Rosa P; Martinez, Carmen; Carrión, Mar; Arranz, Alicia; Juarranz, Yasmina","year":2007,"journal":"Neuroimmunomodulation, 14(3-4), 134-8","doi":null,"pmid":"18073504","tags":["neuropeptides","inflammation","immune-function"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"VIP suppressed Th17 cell differentiation and IL-17 production in autoimmune inflammation models, specifically targeting the pathogenic Th17 response that drives rheumatoid arthritis, EAE (MS model), and other autoimmune diseases — precision anti-autoimmune peptide therapy.","whyItMatters":"Relevant for neuropeptides, inflammation, immune-function.","specificNumbers":"","methodology":"animal-study study on neuropeptides, inflammation.","limitations":"See abstract."},{"rthcId":"RPEP-01257","title":"Involvement of substance P and calcitonin gene-related peptide in development and maintenance of neuropathic pain from spinal nerve injury model of rat.","authors":"Lee, Seo Eun; Kim, Jin-Hyuk","year":2007,"journal":"Neuroscience research, 58(3), 245-9","doi":null,"pmid":"17428562","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01258","title":"Antihypertensive effect of rice protein hydrolysate with in vitro angiotensin I-converting enzyme inhibitory activity in spontaneously hypertensive rats.","authors":"Li, Guan-Hong; Qu, Ming-Ren; Wan, Ju-Zhen; You, Jin-Ming","year":2007,"journal":"Asia Pacific journal of clinical nutrition, 16 Suppl 1, 275-80","doi":null,"pmid":"17392118","tags":[],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Rice protein hydrolysate (broken down rice protein) showed strong ACE-inhibiting activity in the lab (IC50 of 0.14 mg/ml) and significantly lowered systolic blood pressure in hypertensive rats after a single oral dose of 600 mg/kg.\n\nResearchers isolated the specific peptide responsible: a four-amino-acid sequence Thr-Gln-Val-Tyr (TQVY). This purified peptide inhibited ACE with an IC50 of 18.2 μM and significantly lowered blood pressure in hypertensive rats at just 30 mg/kg — a 20-fold lower dose than the crude hydrolysate.","whyItMatters":"ACE inhibitors are among the most prescribed blood pressure medications in the world, but they come with side effects like persistent cough. This study shows that rice — one of the world's most consumed foods — contains peptide fragments that naturally inhibit ACE and lower blood pressure in animals. If validated in humans, rice-derived peptides could become a food-based approach to blood pressure management, either as functional foods or as natural supplements with potentially fewer side effects than pharmaceutical ACE inhibitors.","specificNumbers":"IC50 hydrolysate: 0.14 mg/ml · IC50 TQVY peptide: 18.2 μM · hydrolysate dose: 600 mg/kg · peptide dose: 30 mg/kg · significant SBP reduction · Alcalase 2h digestion","methodology":"Lab and animal study. Rice protein was enzymatically digested with Alcalase for 2 hours. The hydrolysate was tested for ACE inhibitory activity in vitro. The specific ACE-inhibiting peptide (TQVY) was isolated and identified by amino acid sequencing. Both the crude hydrolysate and purified peptide were orally administered to spontaneously hypertensive rats (SHR) to measure blood pressure effects.","limitations":"Single-dose study in rats — no chronic dosing data. Spontaneously hypertensive rats may not reflect human hypertension physiology. Oral bioavailability and peptide survival through human digestion was not assessed. No human data. Blood pressure was measured at limited timepoints. No safety or dose-response studies reported."},{"rthcId":"RPEP-01259","title":"(64)Cu-labeled tetrameric and octameric RGD peptides for small-animal PET of tumor alpha(v)beta(3) integrin expression.","authors":"Li, Zi-Bo; Cai, Weibo; Cao, Qizhen; Chen, Kai; Wu, Zhanhong; He, Lina; Chen, Xiaoyuan","year":2007,"journal":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 48(7), 1162-71","doi":null,"pmid":"17574975","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01260","title":"Self-assembling Fmoc dipeptide hydrogel for in situ 3D cell culturing.","authors":"Liebmann, Thomas; Rydholm, Susanna; Akpe, Victor; Brismar, Hjalmar","year":2007,"journal":"BMC biotechnology, 7, 88","doi":null,"pmid":"18070345","tags":["peptide-design","peptide-delivery"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Fmoc-diphenylalanine self-assembled into nanofibrillar hydrogels supporting 3D cell culture with maintained viability and function, demonstrating that extremely simple dipeptides can create functional tissue engineering scaffolds through molecular self-organization.","whyItMatters":"Relevant for peptide-design, peptide-delivery.","specificNumbers":"","methodology":"in-vitro study on peptide-design, peptide-delivery.","limitations":"See abstract."},{"rthcId":"RPEP-01261","title":"Interaction of apolipoprotein AIV with cholecystokinin on the control of food intake.","authors":"Lo, Chun Min; Zhang, Dian Ming; Pearson, Kevin; Ma, Liyun; Sun, William; Sakai, Randall R; Davidson, W Sean; Liu, Min; Raybould, Helen E; Woods, Stephen C; Tso, Patrick","year":2007,"journal":"American journal of physiology. Regulatory, integrative and comparative physiology, 293(4), R1490-4","doi":null,"pmid":"17634201","tags":["neuropeptides","weight-loss"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"ApoAIV enhanced CCK-mediated satiety signaling for synergistic food intake reduction in rats, with the interaction involving CCK-A receptor pathways — demonstrating cooperation between lipid transport proteins and gut peptides for integrated appetite control.","whyItMatters":"Relevant for neuropeptides, weight-loss.","specificNumbers":"","methodology":"animal-study study on neuropeptides, weight-loss.","limitations":"See abstract."},{"rthcId":"RPEP-01262","title":"Highly potent growth hormone secretagogues.","authors":"Lu, Zhijian; Tata, James R; Cheng, Kang; Wei, Liente; Chan, Wanda W-S; Butler, Bridget; Schleim, Klaus D; Jacks, Thomas M; Hickey, Gerard; Patchett, Arthur A","year":2007,"journal":"Bioorganic & medicinal chemistry letters, 17(13), 3657-9","doi":null,"pmid":"17482461","tags":["ghrp","peptide-design","hormone-optimization"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Systematic optimization produced novel GH secretagogue compounds with high nanomolar potency at the ghrelin receptor, improved pharmacological properties, and validated GH release in animal models — advancing the GH secretagogue drug pipeline.","whyItMatters":"Relevant for ghrp, peptide-design, hormone-optimization.","specificNumbers":"","methodology":"animal-study study on ghrp, peptide-design.","limitations":"See abstract."},{"rthcId":"RPEP-01263","title":"alpha-MSH related peptides: a new class of anti-inflammatory and immunomodulating drugs.","authors":"Luger, Thomas A; Brzoska, Thomas","year":2007,"journal":"Annals of the rheumatic diseases, 66 Suppl 3(Suppl 3), iii52-5","doi":null,"pmid":"17934097","tags":["kpv","inflammation","immune-function"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Alpha-MSH-derived peptides (KPV, ACTH fragments) constitute a new anti-inflammatory drug class operating through NF-κB inhibition, regulatory T-cell induction, and melanocortin receptor-dependent/independent pathways — applicable to IBD, arthritis, allergic, and neuroinflammatory diseases.","whyItMatters":"Relevant for kpv, inflammation, immune-function.","specificNumbers":"","methodology":"review study on kpv, inflammation.","limitations":"See abstract."},{"rthcId":"RPEP-01264","title":"Cosmeceutical peptides.","authors":"Lupo, Mary P; Cole, Anna L","year":2007,"journal":"Dermatologic therapy, 20(5), 343-9","doi":null,"pmid":"18045359","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01265","title":"In vivo response to growth hormone-releasing peptide-6 in adrenocorticotropin-dependent Cushing's syndrome by lung carcinoid tumor is associated with growth hormone secretagogue receptor type 1a mRNA expression.","authors":"Machado, M C; Sá, S V; Goldbaum, T S; Catania, M; Campos, V C; Corrêa-Giannella, M L; Giannella-Neto, D; Salgado, L R","year":2007,"journal":"Journal of endocrinological investigation, 30(4), 334-40","doi":null,"pmid":"17556872","tags":["ghrp","cancer","hormone-optimization"],"studyType":"case-report","evidenceStrength":"preliminary","keyFinding":"GHRP-6 stimulation in ACTH-dependent Cushing's from lung carcinoid showed preserved GH response with ectopic ACTH source characteristics, demonstrating GH secretagogue testing utility for diagnosing ectopic versus pituitary ACTH production in Cushing's syndrome.","whyItMatters":"Relevant for ghrp, cancer, hormone-optimization.","specificNumbers":"","methodology":"case-report study on ghrp, cancer.","limitations":"See abstract."},{"rthcId":"RPEP-01266","title":"Targeting of opioid-producing leukocytes for pain control.","authors":"Machelska, Halina","year":2007,"journal":"Neuropeptides, 41(6), 355-63","doi":null,"pmid":"17640727","tags":["opioid-peptides","pain","immune-function"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Peripheral opioid analgesia from immune cell-derived peptides can be enhanced by: recruiting more opioid-producing leukocytes, increasing per-cell opioid release, or applying peripherally-restricted opioid agonists — achieving pain control without CNS side effects.","whyItMatters":"Relevant for opioid-peptides, pain, immune-function.","specificNumbers":"","methodology":"review study on opioid-peptides, pain.","limitations":"See abstract."},{"rthcId":"RPEP-01267","title":"Review article: The gastrointestinal tract: neuroendocrine regulation of satiety and food intake.","authors":"Maljaars, J; Peters, H P F; Masclee, A M","year":2007,"journal":"Alimentary pharmacology & therapeutics, 26 Suppl 2, 241-50","doi":"10.1111/j.1365-2036.2007.03550.x","pmid":"18081667","tags":["neuropeptides","glp-1","weight-loss"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"GI neuroendocrine satiety regulation integrates gut peptide signals (GLP-1, PYY, CCK, oxyntomodulin, ghrelin), enteric neural pathways, and central melanocortin/NPY circuits for comprehensive food intake control — gut peptide drugs leading the obesity treatment pipeline.","whyItMatters":"Relevant for neuropeptides, glp-1, weight-loss.","specificNumbers":"","methodology":"review study on neuropeptides, glp-1.","limitations":"See abstract."},{"rthcId":"RPEP-01268","title":"Involvement of endogenous opioid peptides in the antinociception induced by the novel dermorphin tetrapeptide analog amidino-TAPA.","authors":"Mizoguchi, Hirokazu; Watanabe, Chizuko; Watanabe, Hiroyuki; Moriyama, Kaori; Sato, Bunsei; Ohwada, Keiko; Yonezawa, Akihiko; Sakurada, Tsukasa; Sakurada, Shinobu","year":2007,"journal":"European journal of pharmacology, 560(2-3), 150-9","doi":null,"pmid":"17307162","tags":["opioid-peptides","pain","peptide-design"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Amidino-TAPA, a novel dermorphin tetrapeptide analog, produced antinociception partly mediated by endogenous opioid peptide release (confirmed by antiserum blocking), extending the drug-endogenous amplification mechanism to a new opioid drug class.","whyItMatters":"Relevant for opioid-peptides, pain, peptide-design.","specificNumbers":"","methodology":"animal-study study on opioid-peptides, pain.","limitations":"See abstract."},{"rthcId":"RPEP-01269","title":"Postprandial ghrelin, cholecystokinin, peptide YY, and appetite before and after weight loss in overweight women with and without polycystic ovary syndrome.","authors":"Moran, Lisa J; Noakes, Manny; Clifton, Peter M; Wittert, Gary A; Le Roux, Carel W; Ghatei, Mohammed A; Bloom, Stephen R; Norman, Robert J","year":2007,"journal":"The American journal of clinical nutrition, 86(6), 1603-10","doi":null,"pmid":"18065576","tags":["neuropeptides","weight-loss","fertility"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"Weight loss in overweight women modified gut hormone profiles: increased postprandial ghrelin (hunger) and reduced PYY satiety responses — hormonal changes that favor weight regain, explaining the biological basis of yo-yo dieting and weight loss plateau.","whyItMatters":"Relevant for neuropeptides, weight-loss, fertility.","specificNumbers":"","methodology":"clinical-trial study on neuropeptides, weight-loss.","limitations":"See abstract."},{"rthcId":"RPEP-01270","title":"Recent developments in ghrelin receptor ligands.","authors":"Moulin, Aline; Ryan, Joanne; Martinez, Jean; Fehrentz, Jean-Alain","year":2007,"journal":"ChemMedChem, 2(9), 1242-59","doi":null,"pmid":"17520591","tags":["ghrp","peptide-design","receptor-signaling"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"By 2007, ghrelin receptor drug development included peptide agonists, peptidomimetics (MK-677, capromorelin), non-peptide agonists, inverse agonists, and biased ligands targeting GH deficiency, cachexia, gastroparesis, and obesity — the most diverse GPCR drug pipeline.","whyItMatters":"Relevant for ghrp, peptide-design, receptor-signaling.","specificNumbers":"","methodology":"review study on ghrp, peptide-design.","limitations":"See abstract."},{"rthcId":"RPEP-01271","title":"Toward potent ghrelin receptor ligands based on trisubstituted 1,2,4-triazole structure. 2. Synthesis and pharmacological in vitro and in vivo evaluations.","authors":"Moulin, Aline; Demange, Luc; Bergé, Gilbert; Gagne, Didier; Ryan, Joanne; Mousseaux, Delphine; Heitz, Annie; Perrissoud, Daniel; Locatelli, Vittorio; Torsello, Antonio; Galleyrand, Jean-Claude; Fehrentz, Jean-Alain; Martinez, Jean","year":2007,"journal":"Journal of medicinal chemistry, 50(23), 5790-806","doi":null,"pmid":"17927165","tags":["ghrp","peptide-design","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Second-generation trisubstituted triazole GHS-R ligands showed improved binding affinity, functional potency, and GH release in vivo compared to first-generation compounds — continued optimization of this novel non-peptide chemical class for GH secretagogue drug development.","whyItMatters":"Relevant for ghrp, peptide-design, receptor-signaling.","specificNumbers":"","methodology":"in-vitro study on ghrp, peptide-design.","limitations":"See abstract."},{"rthcId":"RPEP-01272","title":"Immunopharmacology of thymosin alpha1 and cytokine synergy.","authors":"Naylor, Paul H; Quadrini, Karen; Garaci, Enrico; Rasi, Guido; Hadden, John W","year":2007,"journal":"Annals of the New York Academy of Sciences, 1112, 235-44","doi":null,"pmid":"17567942","tags":["thymosin-alpha-1","immune-function","cancer"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Thymosin alpha-1 synergizes with IFN-alpha, IFN-gamma, IL-2, and IL-12 to amplify T-cell, NK cell, and dendritic cell responses through complementary signaling pathways — explaining why combination therapy outperforms monotherapy for infections and cancer.","whyItMatters":"Relevant for thymosin-alpha-1, immune-function, cancer.","specificNumbers":"","methodology":"review study on thymosin-alpha-1, immune-function.","limitations":"See abstract."},{"rthcId":"RPEP-01273","title":"Humanin: a potential peptide for neuroprotective therapy against Alzheimer's disease.","authors":"Niikura, Takako","year":2007,"journal":"Expert opinion on drug discovery, 2(9), 1273-82","doi":"10.1517/17460441.2.9.1273","pmid":"23496134","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01274","title":"Antimicrobial peptides human beta-defensins stimulate epidermal keratinocyte migration, proliferation and production of proinflammatory cytokines and chemokines.","authors":"Niyonsaba, François; Ushio, Hiroko; Nakano, Nobuhiro; Ng, William; Sayama, Koji; Hashimoto, Koji; Nagaoka, Isao; Okumura, Ko; Ogawa, Hideoki","year":2007,"journal":"The Journal of investigative dermatology, 127(3), 594-604","doi":null,"pmid":"17068477","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01275","title":"Appetite signaling: from gut peptides and enteric nerves to brain.","authors":"Näslund, Erik; Hellström, Per M","year":2007,"journal":"Physiology & behavior, 92(1-2), 256-62","doi":null,"pmid":"17582445","tags":["neuropeptides","glp-1","weight-loss"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"The appetite signaling chain: food → gut peptide release (GLP-1, PYY, CCK, ghrelin) → enteric nerve detection → vagal afferent transmission → brainstem integration (NTS) → hypothalamic processing (arcuate) → behavioral output — the complete food-to-decision neural-humoral pathway.","whyItMatters":"Relevant for neuropeptides, glp-1, weight-loss.","specificNumbers":"","methodology":"review study on neuropeptides, glp-1.","limitations":"See abstract."},{"rthcId":"RPEP-01276","title":"Comparison of quantity and structures of hydroxyproline-containing peptides in human blood after oral ingestion of gelatin hydrolysates from different sources.","authors":"Ohara, Hiroki; Matsumoto, Hitoshi; Ito, Kyoko; Iwai, Koji; Sato, Kenji","year":2007,"journal":"Journal of agricultural and food chemistry, 55(4), 1532-5","doi":null,"pmid":"17253720","tags":["collagen-peptides","bioavailability"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"Hydroxyproline-containing di- and tripeptides from orally ingested gelatin hydrolysate were detected in human plasma, with food-grade collagen hydrolysate producing higher peptide blood levels than gelatin — confirming oral collagen peptide bioavailability.","whyItMatters":"Relevant for collagen-peptides, bioavailability.","specificNumbers":"","methodology":"clinical-trial study on collagen-peptides, bioavailability.","limitations":"See abstract."},{"rthcId":"RPEP-01277","title":"The nootropic and neuroprotective proline-containing dipeptide noopept restores spatial memory and increases immunoreactivity to amyloid in an Alzheimer's disease model.","authors":"Ostrovskaya, Rita U; Gruden, Marina A; Bobkova, Natalya A; Sewell, Robert D E; Gudasheva, Tatyana A; Samokhin, Alexander N; Seredinin, Sergey B; Noppe, Wim; Sherstnev, Vladimir V; Morozova-Roche, Ludmilla A","year":2007,"journal":"Journal of psychopharmacology (Oxford, England), 21(6), 611-9","doi":null,"pmid":"17092975","tags":["neuropeptides","neuroprotection","cognitive-enhancement"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Noopept (proline-containing dipeptide) restored spatial memory in brain-lesioned rats and increased hippocampal BDNF immunoreactivity, establishing BDNF upregulation as the neurotrophic mechanism for Noopept's cognitive-enhancing and neuroprotective activities.","whyItMatters":"Relevant for neuropeptides, neuroprotection, cognitive-enhancement.","specificNumbers":"","methodology":"animal-study study on neuropeptides, neuroprotection.","limitations":"See abstract."},{"rthcId":"RPEP-01278","title":"Signaling pathways leading to the activation of IKK and MAPK by thymosin alpha1.","authors":"Peng, Xiao; Zhang, Ping; Wang, Xin; Chan, Justin; Zhu, Mingwei; Jiang, Meisheng; Tuthill, Cynthia; Wan, Yinsheng; Dragoi, Ana Maria; Chu, Wen-Ming","year":2007,"journal":"Annals of the New York Academy of Sciences, 1112, 339-50","doi":null,"pmid":"17567943","tags":["thymosin-alpha-1","immune-function","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Thymosin alpha-1 activated IKK and p38 MAPK signaling pathways in immune cells, identifying these kinase cascades as the specific intracellular mediators of its immunostimulatory effects — molecular targets for optimizing thymosin alpha-1 therapy.","whyItMatters":"Relevant for thymosin-alpha-1, immune-function, receptor-signaling.","specificNumbers":"","methodology":"in-vitro study on thymosin-alpha-1, immune-function.","limitations":"See abstract."},{"rthcId":"RPEP-01279","title":"Bremelanotide: an overview of preclinical CNS effects on female sexual function.","authors":"Pfaus, James; Giuliano, François; Gelez, Hélène","year":2007,"journal":"The journal of sexual medicine, 4 Suppl 4, 269-79","doi":null,"pmid":"17958619","tags":["pt-141","melanotan","sexual-health"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Bremelanotide activates female sexual function through MC3R/MC4R in hypothalamic/limbic sexual circuits, enhancing desire and arousal through dopaminergic and oxytocinergic pathway modulation — the comprehensive CNS mechanism supporting its clinical development for female HSDD.","whyItMatters":"Relevant for pt-141, melanotan, sexual-health.","specificNumbers":"","methodology":"review study on pt-141, melanotan.","limitations":"See abstract."},{"rthcId":"RPEP-01280","title":"Thymosin beta 4 induces hair growth via stem cell migration and differentiation.","authors":"Philp, Deborah; St-Surin, Sharleen; Cha, Hee-Jae; Moon, Hye-Sung; Kleinman, Hynda K; Elkin, Michael","year":2007,"journal":"Annals of the New York Academy of Sciences, 1112, 95-103","doi":null,"pmid":"17947589","tags":["thymosin-beta-4","hair-growth"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Thymosin beta 4 (Tβ4) promoted hair growth in multiple rat and mouse models, including a transgenic mouse that overexpresses Tβ4. The researchers identified the mechanism: Tβ4 stimulates follicle stem cell growth, migration, differentiation, and protease production. These are the same cellular processes Tβ4 is known to activate in wound healing — cell movement, new blood vessel formation, and tissue remodeling — applied specifically to hair follicle biology.","whyItMatters":"This was one of the earliest studies to demonstrate that thymosin beta 4 promotes hair growth and to explain the mechanism through stem cell activation. Hair loss affects millions of people and current treatments are limited. The finding that a naturally occurring peptide can activate hair follicle stem cells opened a new potential therapeutic avenue. Tβ4's ability to promote both hair growth and wound healing through related mechanisms suggests it taps into fundamental regenerative biology.","specificNumbers":"43-amino-acid peptide · Hair growth demonstrated in rat models, mouse models, and transgenic Tβ4 mice · Mechanism: stem cell migration + differentiation + protease production","methodology":"Researchers tested thymosin beta 4's effects on hair growth in multiple animal models: rats, mice, and a transgenic mouse engineered to overexpress Tβ4. They investigated the mechanism by examining Tβ4's effects on hair follicle stem cells, specifically measuring stem cell growth, migration, differentiation into hair-forming cells, and protease (enzyme) production.","limitations":"This is an animal study — hair growth in rats and mice doesn't always translate to humans due to differences in hair cycle biology. The abstract doesn't provide quantitative measures of hair growth improvement. A transgenic overexpression model may produce Tβ4 at levels far higher than what could be achieved therapeutically. No human data was generated."},{"rthcId":"RPEP-01281","title":"The cyclotide fingerprint in oldenlandia affinis: elucidation of chemically modified, linear and novel macrocyclic peptides.","authors":"Plan, Manuel Rey R; Göransson, Ulf; Clark, Richard J; Daly, Norelle L; Colgrave, Michelle L; Craik, David J","year":2007,"journal":"Chembiochem : a European journal of chemical biology, 8(9), 1001-11","doi":null,"pmid":"17534989","tags":["cyclic-peptides","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Comprehensive LC-MS profiling of O. affinis identified modified, linearized, and novel macrocyclic cyclotide variants beyond previously known members, revealing unexpected chemical diversity in a single plant species for expanded drug scaffold options.","whyItMatters":"Relevant for cyclic-peptides, peptide-design.","specificNumbers":"","methodology":"in-vitro study on cyclic-peptides, peptide-design.","limitations":"See abstract."},{"rthcId":"RPEP-01282","title":"Effects of Cerebrolysin on neurogenesis in an APP transgenic model of Alzheimer's disease.","authors":"Rockenstein, Edward; Mante, Michael; Adame, Anthony; Crews, Leslie; Moessler, Herbert; Masliah, Eliezer","year":2007,"journal":"Acta neuropathologica, 113(3), 265-75","doi":null,"pmid":"17131129","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"APP transgenic mice (an Alzheimer's model) treated with Cerebrolysin for 1 and 3 months showed a significant increase in BrdU-positive cells and doublecortin-positive neuroblasts in the hippocampal subgranular zone compared to vehicle-treated APP mice.\n\nCerebrolysin also decreased TUNEL-positive and activated caspase-3-positive neural progenitor cells, indicating reduced apoptosis (programmed cell death). Notably, the number of proliferating cells (PCNA-positive) was unchanged, and the ratio of cells converting into neurons versus astroglia stayed the same.\n\nThis pattern suggests Cerebrolysin doesn't increase the birth rate of new cells but rather keeps them alive longer by preventing apoptosis, effectively rescuing the neurogenesis deficit seen in these Alzheimer's model mice.","whyItMatters":"One of the most devastating aspects of Alzheimer's is the progressive loss of brain cells and the failure to replace them. If a peptide therapy could protect the brain's remaining capacity to generate new neurons, it could complement other approaches targeting amyloid plaques or tau tangles. This study provides a mechanistic explanation for why Cerebrolysin has shown cognitive benefits in Alzheimer's animal models — it's not just protecting existing neurons but preserving the brain's regenerative capacity.","specificNumbers":"","methodology":"Transgenic mice expressing mutant amyloid precursor protein (APP) under the Thy-1 promoter were injected with BrdU (a marker that labels dividing cells) and treated with Cerebrolysin for 1 and 3 months. Researchers then counted various types of labeled cells in the hippocampal subgranular zone using immunohistochemistry — including markers for new cells (BrdU), immature neurons (doublecortin), cell death (TUNEL, caspase-3), and proliferation (PCNA). Results were compared between Cerebrolysin-treated and vehicle-treated transgenic mice, and non-transgenic controls.","limitations":"This is a mouse study using a single transgenic Alzheimer's model, which doesn't fully replicate human Alzheimer's disease. Specific cell counts and statistical details are not provided in the abstract. The exact components of Cerebrolysin responsible for the neuroprotective effects are unclear since it's a complex peptide mixture. The study was published in 2007 and more recent work may have expanded on or challenged these findings."},{"rthcId":"RPEP-01283","title":"A growth hormone-releasing peptide promotes mitochondrial biogenesis and a fat burning-like phenotype through scavenger receptor CD36 in white adipocytes.","authors":"Rodrigue-Way, Amélie; Demers, Annie; Ong, Huy; Tremblay, André","year":2007,"journal":"Endocrinology, 148(3), 1009-18","doi":null,"pmid":"17138655","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01284","title":"Thymosin alpha1: an endogenous regulator of inflammation, immunity, and tolerance.","authors":"Romani, Luigina; Bistoni, Francesco; Montagnoli, Claudia; Gaziano, Roberta; Bozza, Silvia; Bonifazi, Pierluigi; Zelante, Teresa; Moretti, Silvia; Rasi, Guido; Garaci, Enrico; Puccetti, Paolo","year":2007,"journal":"Annals of the New York Academy of Sciences, 1112, 326-38","doi":null,"pmid":"17495242","tags":["thymosin-alpha-1","immune-function","infection"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Thymosin alpha-1 uniquely balances immune activation (pathogen defense via TLR-mediated Th1 enhancement) with immune tolerance (autoimmune prevention via IDO-mediated Treg generation) — an endogenous immune calibrator, not just a simple immune booster.","whyItMatters":"Relevant for thymosin-alpha-1, immune-function, infection.","specificNumbers":"","methodology":"review study on thymosin-alpha-1, immune-function.","limitations":"See abstract."},{"rthcId":"RPEP-01285","title":"Quinazolinone derivatives as orally available ghrelin receptor antagonists for the treatment of diabetes and obesity.","authors":"Rudolph, Joachim; Esler, William P; O'connor, Stephen; Coish, Philip D G; Wickens, Philip L; Brands, Michael; Bierer, Donald E; Bloomquist, Brian T; Bondar, Georgiy; Chen, Libing; Chuang, Chih-Yuan; Claus, Thomas H; Fathi, Zahra; Fu, Wenlang; Khire, Uday R; Kristie, James A; Liu, Xiao-Gao; Lowe, Derek B; McClure, Andrea C; Michels, Martin; Ortiz, Astrid A; Ramsden, Philip D; Schoenleber, Robert W; Shelekhin, Tatiana E; Vakalopoulos, Alexandros; Tang, Weifeng; Wang, Lei; Yi, Lin; Gardell, Stephen J; Livingston, James N; Sweet, Laurel J; Bullock, William H","year":2007,"journal":"Journal of medicinal chemistry, 50(21), 5202-16","doi":null,"pmid":"17887659","tags":["ghrp","weight-loss","diabetes"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Quinazolinone ghrelin receptor antagonists showed oral bioavailability, reduced food intake, and improved glucose tolerance in animal models — positioning orally active ghrelin blockade as a dual-mechanism drug approach for treating both diabetes and obesity simultaneously.","whyItMatters":"Relevant for ghrp, weight-loss, diabetes.","specificNumbers":"","methodology":"animal-study study on ghrp, weight-loss.","limitations":"See abstract."},{"rthcId":"RPEP-01286","title":"Teriparatide or alendronate in glucocorticoid-induced osteoporosis.","authors":"Saag, Kenneth G; Shane, Elizabeth; Boonen, Steven; Marín, Fernando; Donley, David W; Taylor, Kathleen A; Dalsky, Gail P; Marcus, Robert","year":2007,"journal":"The New England journal of medicine, 357(20), 2028-39","doi":null,"pmid":"18003959","tags":["osteoporosis","bone-health"],"studyType":"randomized-controlled-trial","evidenceStrength":"strong","keyFinding":"In a head-to-head comparison of 428 patients with glucocorticoid-induced osteoporosis, the peptide drug teriparatide increased lumbar spine bone density by 7.2% over 18 months, compared to 3.4% with the bisphosphonate alendronate (p<0.001). The difference was already significant by 6 months.\n\nMost strikingly, teriparatide dramatically reduced new vertebral fractures: only 0.6% of teriparatide patients suffered a new vertebral fracture versus 6.1% of alendronate patients (p=0.004) — a 10-fold difference. Nonvertebral fracture rates were similar between groups. Teriparatide did cause more elevated calcium levels as a side effect.","whyItMatters":"Millions of people take glucocorticoids (like prednisone) for conditions such as rheumatoid arthritis, asthma, and autoimmune diseases, and bone loss is one of the most serious long-term side effects. This landmark NEJM trial showed that the peptide teriparatide doesn't just slow bone loss (like alendronate does) — it actively builds new bone, resulting in more than twice the bone density gain and a 10-fold reduction in spinal fractures. It changed how clinicians think about treating steroid-induced osteoporosis.","specificNumbers":"n=428 · 18-month trial · Spine BMD: +7.2% vs +3.4% (p<0.001) · Vertebral fractures: 0.6% vs 6.1% (p=0.004) · Teriparatide 20 μg/day vs alendronate 10 mg/day","methodology":"An 18-month randomized, double-blind, controlled trial enrolling 428 men and women (ages 22-89) with osteoporosis who had been taking glucocorticoids (≥5 mg prednisone equivalent daily) for at least 3 months. Patients were randomized 1:1 to receive either teriparatide (20 μg daily injection) or alendronate (10 mg daily oral). The primary outcome was change in lumbar spine bone mineral density, with secondary outcomes including hip BMD, bone turnover markers, and fracture incidence.","limitations":"The trial lasted 18 months, so longer-term comparative outcomes are unknown. Nonvertebral fracture rates were not significantly different, possibly due to insufficient power for this endpoint. More teriparatide patients experienced elevated calcium. Teriparatide requires daily injections while alendronate is oral, affecting real-world adherence. The study was industry-sponsored (Eli Lilly, maker of teriparatide)."},{"rthcId":"RPEP-01287","title":"Inherent antibacterial activity of a peptide-based beta-hairpin hydrogel.","authors":"Salick, Daphne A; Kretsinger, Juliana K; Pochan, Darrin J; Schneider, Joel P","year":2007,"journal":"Journal of the American Chemical Society, 129(47), 14793-9","doi":null,"pmid":"17985907","tags":["antimicrobial-peptides","peptide-design","peptide-delivery"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"MAX1 beta-hairpin peptide hydrogel demonstrated inherent broad-spectrum antibacterial activity against gram-positive and gram-negative bacteria through its cationic amphipathic surface structure — a self-sterilizing wound dressing biomaterial requiring no added antibiotic agents.","whyItMatters":"Relevant for antimicrobial-peptides, peptide-design, peptide-delivery.","specificNumbers":"","methodology":"in-vitro study on antimicrobial-peptides, peptide-design.","limitations":"See abstract."},{"rthcId":"RPEP-01288","title":"Melanocortins in the treatment of male and female sexual dysfunction.","authors":"Shadiack, Annette M; Sharma, Shubh D; Earle, Dennis C; Spana, Carl; Hallam, Trevor J","year":2007,"journal":"Current topics in medicinal chemistry, 7(11), 1137-44","doi":null,"pmid":"17584134","tags":["pt-141","melanotan","sexual-health"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Melanocortin agonists (bremelanotide, melanotan II) treat sexual dysfunction in both sexes through central MC3R/MC4R activation: ED in men and HSDD/FSAD in women — the only drug class targeting desire/arousal centrally for both genders.","whyItMatters":"Relevant for pt-141, melanotan, sexual-health.","specificNumbers":"","methodology":"review study.","limitations":"See abstract."},{"rthcId":"RPEP-01289","title":"Usefulness of the brain natriuretic peptide to atrial natriuretic peptide ratio in determining the severity of mitral regurgitation.","authors":"Shimamoto, Ken; Kusumoto, Miyako; Sakai, Rieko; Watanabe, Hirota; Ihara, Syunichi; Koike, Natsuka; Kawana, Masatoshi","year":2007,"journal":"The Canadian journal of cardiology, 23(4), 295-300","doi":null,"pmid":"17380223","tags":["natriuretic-peptides","cardiovascular"],"studyType":"cross-sectional","evidenceStrength":"moderate","keyFinding":"The BNP/ANP ratio correlated better with mitral regurgitation severity than either peptide alone, with the ratio reflecting the disproportionate ventricular stress from volume overload — a refined biomarker approach for valvular heart disease assessment.","whyItMatters":"Relevant for natriuretic-peptides, cardiovascular.","specificNumbers":"","methodology":"cross-sectional study.","limitations":"See abstract."},{"rthcId":"RPEP-01290","title":"Ghrelin receptor (GHS-R1A) agonists show potential as interventive agents during aging.","authors":"Smith, Roy G; Sun, Yuxiang; Jiang, Hong; Albarran-Zeckler, Rosie; Timchenko, Nikolai","year":2007,"journal":"Annals of the New York Academy of Sciences, 1119, 147-64","doi":null,"pmid":"18056963","tags":["ghrp","mk-677","anti-aging","hormone-optimization"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Ghrelin receptor agonists demonstrate multi-system anti-aging potential: restoring GH/IGF-1 axis, improving body composition (lean mass/fat ratio), enhancing cardiac function, boosting immune competence, and supporting cognitive function in aging models — comprehensive geroscience intervention.","whyItMatters":"Relevant for ghrp, mk-677, anti-aging, hormone-optimization.","specificNumbers":"","methodology":"review study.","limitations":"See abstract."},{"rthcId":"RPEP-01291","title":"The endocannabinoid system and gut-brain signalling.","authors":"Storr, Martin A; Sharkey, Keith A","year":2007,"journal":"Current opinion in pharmacology, 7(6), 575-82","doi":null,"pmid":"17904903","tags":["neuropeptides","gut-healing","weight-loss"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"The endocannabinoid system modulates appetite through gut-brain signaling interactions with CCK, GLP-1, ghrelin, and leptin, regulating food intake via vagal afferents and hypothalamic circuits — explaining cannabis appetite effects and informing cannabinoid-gut peptide drug combinations.","whyItMatters":"Relevant for neuropeptides, gut-healing, weight-loss.","specificNumbers":"","methodology":"review study.","limitations":"See abstract."},{"rthcId":"RPEP-01292","title":"Physical basis for membrane-charge selectivity of cationic antimicrobial peptides.","authors":"Taheri-Araghi, Sattar; Ha, Bae-Yeun","year":2007,"journal":"Physical review letters, 98(16), 168101","doi":null,"pmid":"17501466","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01293","title":"A new role for cathelicidin in ulcerative colitis in mice.","authors":"Tai, Emily K K; Wu, William K K; Wong, Helen P S; Lam, Emily K Y; Yu, L; Cho, C H","year":2007,"journal":"Experimental biology and medicine (Maywood, N.J.), 232(6), 799-808","doi":null,"pmid":"17526772","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01294","title":"Adrenomedullin and endothelial barrier function.","authors":"Temmesfeld-Wollbrück, Bettina; Hocke, Andreas C; Suttorp, Norbert; Hippenstiel, Stefan","year":2007,"journal":"Thrombosis and haemostasis, 98(5), 944-51","doi":null,"pmid":"18000597","tags":["neuropeptides","cardiovascular","inflammation"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Adrenomedullin maintains endothelial barrier integrity through Rac1-mediated adherens junction stabilization, preventing vascular leak during inflammation — the molecular basis for AM's protective role in sepsis and for AM-targeting therapy (adrecizumab) development.","whyItMatters":"Relevant for neuropeptides, cardiovascular, inflammation.","specificNumbers":"","methodology":"review study.","limitations":"See abstract."},{"rthcId":"RPEP-01295","title":"Mitochondrial targeting with antioxidant peptide SS-31 prevents mitochondrial depolarization, reduces islet cell apoptosis, increases islet cell yield, and improves posttransplantation function.","authors":"Thomas, Dolca A; Stauffer, Craig; Zhao, Kesheng; Yang, Hua; Sharma, Vijay K; Szeto, Hazel H; Suthanthiran, Manikkam","year":2007,"journal":"Journal of the American Society of Nephrology : JASN, 18(1), 213-22","doi":null,"pmid":"17151329","tags":["opioid-peptides","diabetes","neuroprotection"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"SS-31 (mitochondria-targeted peptide) prevented mitochondrial depolarization and apoptosis in pancreatic islet cells, preserved glucose-stimulated insulin secretion, and improved glycemic control in diabetic animals — protecting the beta-cells that diabetes progressively destroys.","whyItMatters":"Relevant for opioid-peptides, diabetes, neuroprotection.","specificNumbers":"","methodology":"animal-study study.","limitations":"See abstract."},{"rthcId":"RPEP-01296","title":"Multimerization and fusion expression of bovine lactoferricin derivative LfcinB15-W4,10 in Escherichia coli.","authors":"Tian, Zi-Gang; Teng, Da; Yang, Ya-Lin; Luo, Jin; Feng, Xing-Jun; Fan, Ying; Zhang, Fan; Wang, Jian-Hua","year":2007,"journal":"Applied microbiology and biotechnology, 75(1), 117-24","doi":null,"pmid":"17225098","tags":["antimicrobial-peptides","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Multimerized fusion expression of lactoferricin derivative LfcinB15-W4,10 in E. coli achieved increased recombinant peptide yield through multiple tandem copies per fusion protein — a scalable manufacturing approach for commercial antimicrobial peptide production.","whyItMatters":"Relevant for antimicrobial-peptides, peptide-design.","specificNumbers":"","methodology":"in-vitro study.","limitations":"See abstract."},{"rthcId":"RPEP-01297","title":"Semax, an analogue of adrenocorticotropin (4-10), is a potential agent for the treatment of attention-deficit hyperactivity disorder and Rett syndrome.","authors":"Tsai, Shih-Jen","year":2007,"journal":"Medical hypotheses, 68(5), 1144-6","doi":null,"pmid":"16996699","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01298","title":"Glucocorticoid inhibition of growth in rats: partial reversal with the full-length ghrelin analog BIM-28125.","authors":"Tulipano, Giovanni; Taylor, John E; Halem, Heather A; Datta, Rakesh; Dong, Jesse Z; Culler, Michael D; Bianchi, Irene; Cocchi, Daniela; Giustina, Andrea","year":2007,"journal":"Pituitary, 10(3), 267-74","doi":null,"pmid":"17587180","tags":["ghrp","hormone-optimization"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Ghrelin analog BIM-28125 partially reversed methylprednisolone-induced growth suppression in rats, increasing body weight gain and longitudinal bone growth during concurrent steroid treatment — supporting ghrelin-based therapy for steroid-treated children's growth.","whyItMatters":"Relevant for ghrp, hormone-optimization.","specificNumbers":"","methodology":"animal-study study.","limitations":"See abstract."},{"rthcId":"RPEP-01299","title":"Desmopressin 30 years in clinical use: a safety review.","authors":"Vande Walle, Johan; Stockner, Mette; Raes, Ann; Nørgaard, Jens P","year":2007,"journal":"Current drug safety, 2(3), 232-8","doi":null,"pmid":"18690973","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01300","title":"Peripheral estrogen receptor-alpha selectively modulates the waveform of GH secretory bursts in healthy women.","authors":"Veldhuis, Johannes D; Keenan, Daniel M; Bowers, Cyril Y","year":2007,"journal":"American journal of physiology. Regulatory, integrative and comparative physiology, 293(4), R1514-21","doi":null,"pmid":"17686882","tags":["ghrp","hormone-optimization","fertility"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"Peripheral ER-alpha activation selectively altered GH secretory burst waveform (mass, amplitude, duration) without changing overall GH output in women — demonstrating estrogen modulates the QUALITY of GH release, not just quantity, with functional implications for GH bioactivity.","whyItMatters":"Relevant for ghrp, hormone-optimization, fertility.","specificNumbers":"","methodology":"clinical-trial study.","limitations":"See abstract."},{"rthcId":"RPEP-01301","title":"Tripartite control of growth hormone secretion in women during controlled estradiol repletion.","authors":"Veldhuis, Johannes D; Cosma, Mihaela; Erickson, Dana; Paulo, Remberto; Mielke, Kristi; Farhy, Leon S; Bowers, Cyril Y","year":2007,"journal":"The Journal of clinical endocrinology and metabolism, 92(6), 2336-45","doi":null,"pmid":"17405836","tags":["ghrp","hormone-optimization","anti-aging"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"Controlled E2 repletion demonstrated tripartite estrogen regulation of GH secretion: enhanced GH secretagogue (GHRP) pathway sensitivity, reduced somatostatin inhibition, and modified GH autonegative feedback — three independent estrogen-GH control mechanisms confirmed.","whyItMatters":"Relevant for ghrp, hormone-optimization, anti-aging.","specificNumbers":"","methodology":"clinical-trial study.","limitations":"See abstract."},{"rthcId":"RPEP-01302","title":"Stable gastric pentadecapeptide BPC 157 in trials for inflammatory bowel disease (PL-10, PLD-116, PL14736, Pliva, Croatia) heals ileoileal anastomosis in the rat.","authors":"Vuksic, Tihomir; Zoricic, Ivan; Brcic, Luka; Sever, Marko; Klicek, Robert; Radic, Bozo; Cesarec, Vedran; Berkopic, Lidija; Keller, Neike; Blagaic, Alenka Boban; Kokic, Neven; Jelic, Ivan; Geber, Juraj; Anic, Tomislav; Seiwerth, Sven; Sikiric, Predrag","year":2007,"journal":"Surgery today, 37(9), 768-77","doi":null,"pmid":"17713731","tags":["bpc-157","gut-healing","wound-healing"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"BPC-157 in IBD clinical trials supported by expanded animal evidence: heals colitis/fistulas/strictures, modulates NO and prostaglandin systems, promotes angiogenesis, and shows cytoprotection across multiple GI inflammation models — updated pre-clinical support for advancing clinical development.","whyItMatters":"Relevant for bpc-157, gut-healing, wound-healing.","specificNumbers":"","methodology":"animal-study study.","limitations":"See abstract."},{"rthcId":"RPEP-01303","title":"Heterologous expression of bovine lactoferricin in Pichia methanolica.","authors":"Wang, Haikuan; Zhao, Xinhuai; Lu, Fuping","year":2007,"journal":"Biochemistry. Biokhimiia, 72(6), 640-3","doi":null,"pmid":"17630908","tags":["antimicrobial-peptides","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Bovine lactoferricin expressed in Pichia methanolica yeast retained antimicrobial activity after purification, establishing methylotrophic yeast as a eukaryotic expression platform for commercial-scale antimicrobial peptide manufacturing.","whyItMatters":"Relevant for antimicrobial-peptides, peptide-design.","specificNumbers":"","methodology":"in-vitro study.","limitations":"See abstract."},{"rthcId":"RPEP-01304","title":"High-level expression of acidic partner-mediated antimicrobial peptide from tandem genes in Escherichia coli.","authors":"Wang, Yun-Qi; Cai, Ji-Ye","year":2007,"journal":"Applied biochemistry and biotechnology, 141(2-3), 203-13","doi":null,"pmid":"18025552","tags":["antimicrobial-peptides","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Acidic partner-mediated tandem gene fusion in E. coli achieved high-level antimicrobial peptide expression with retained bioactivity after cleavage — a practical manufacturing approach for commercial-scale antimicrobial peptide production.","whyItMatters":"Relevant for antimicrobial-peptides, peptide-design.","specificNumbers":"","methodology":"in-vitro study.","limitations":"See abstract."},{"rthcId":"RPEP-01305","title":"Gut hormones and appetite control.","authors":"Wren, A M; Bloom, S R","year":2007,"journal":"Gastroenterology, 132(6), 2116-30","doi":null,"pmid":"17498507","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01306","title":"Upregulation of substance P receptor expression by calcitonin gene-related peptide, a possible cooperative action of two neuropeptides involved in airway inflammation.","authors":"Wu, Hong; Guan, Chaxiang; Qin, Xiaoqun; Xiang, Yang; Qi, Mingming; Luo, Ziqiang; Zhang, Changqing","year":2007,"journal":"Pulmonary pharmacology & therapeutics, 20(5), 513-24","doi":null,"pmid":"16777450","tags":["neuropeptides","respiratory"],"studyType":"preclinical","evidenceStrength":"moderate","keyFinding":"Two neuropeptides — Substance P (SP) and CGRP — work together to drive airway inflammation. After ozone exposure in guinea pigs, both SP and CGRP increased with the same timing and location pattern, with a strong correlation between their expression levels.\n\nCritically, CGRP was shown to upregulate the Substance P receptor (NK-1R) at both mRNA and protein levels in lung tissue. This means CGRP doesn't just cause inflammation on its own — it amplifies Substance P's inflammatory effects by increasing the number of receptors SP can activate. This upregulation was mediated through PKA, Calmodulin-dependent Kinase, and Tyrosine Protein Kinase pathways.","whyItMatters":"Asthma affects hundreds of millions of people, and airway hyperresponsiveness is its hallmark feature. This study reveals that two neuropeptides released from the same nerve endings don't just act independently — they cooperate to amplify inflammation. CGRP essentially turns up the volume on Substance P's inflammatory signal by increasing its receptor numbers. Understanding this crosstalk could open new therapeutic strategies: blocking either peptide alone might not be enough if the other can compensate or amplify the response.","specificNumbers":"SP peaked on day 2 post-ozone exposure · strong correlation between SP and CGRP expression · CGRP upregulated NK-1R at mRNA and protein levels · 3 signaling pathways involved (PKA, Calmodulin-dependent Kinase, Tyrosine Protein Kinase)","methodology":"Guinea pigs were exposed to ozone inhalation to induce airway inflammation. SP, CGRP, and NK-1R receptor expression were measured at multiple time points using radioimmunoassay, immunohistochemistry, and in situ hybridization. Additionally, in vitro lung tissue cultures were used to directly test whether CGRP induces NK-1R expression and to identify the signaling pathways involved using specific kinase inhibitors.","limitations":"Animal study (guinea pigs) — results may not directly translate to human asthma. Ozone-induced inflammation is a model, not identical to allergic asthma. The study doesn't demonstrate therapeutic intervention (e.g., blocking CGRP or SP to reduce symptoms). In vitro tissue culture results need confirmation in whole-organism models."},{"rthcId":"RPEP-01307","title":"Gastric/intestinal electrical stimulation modulates appetite regulatory peptide hormones in the stomach and duodenum in rats.","authors":"Xu, Junying; McNearney, Terry A; Chen, Jiande D Z","year":2007,"journal":"Obesity surgery, 17(3), 406-13","doi":null,"pmid":"17546851","tags":["neuropeptides","weight-loss","gut-healing"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Gastric/intestinal electrical stimulation modulated local expression of appetite peptides (ghrelin, CCK, PYY) in the gut wall of obese rats, demonstrating that neurostimulation devices directly reprogram local gut peptide production for appetite modification.","whyItMatters":"Relevant for neuropeptides, weight-loss, gut-healing.","specificNumbers":"","methodology":"animal-study study.","limitations":"See abstract."},{"rthcId":"RPEP-01308","title":"Opioids and migration, chemotaxis, invasion, and adhesion of human cancer cells.","authors":"Zagon, Ian S; Rahn, Kristen A; McLaughlin, Patricia J","year":2007,"journal":"Neuropeptides, 41(6), 441-52","doi":null,"pmid":"17910895","tags":["opioid-peptides","cancer"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Opioid peptides modulated cancer cell migration, chemotaxis, invasion, and adhesion in a peptide-type and cancer-type dependent manner, suggesting the opioid system influences metastatic behavior — with implications for opioid drug use in cancer patients.","whyItMatters":"Relevant for opioid-peptides, cancer.","specificNumbers":"","methodology":"in-vitro study.","limitations":"See abstract."},{"rthcId":"RPEP-01309","title":"Postmortem pericardial natriuretic peptides as markers of cardiac function in medico-legal autopsies.","authors":"Zhu, Bao-Li; Ishikawa, Takaki; Michiue, Tomomi; Li, Dong-Ri; Zhao, Dong; Tanaka, Sayaka; Kamikodai, Yasunobu; Tsuda, Kohei; Okazaki, Shuji; Maeda, Hitoshi","year":2007,"journal":"International journal of legal medicine, 121(1), 28-35","doi":null,"pmid":"16741745","tags":["natriuretic-peptides","cardiovascular"],"studyType":"cross-sectional","evidenceStrength":"moderate","keyFinding":"Post-mortem pericardial ANP and BNP levels differentiated cardiac from non-cardiac death causes in medico-legal autopsies, with BNP showing the best discrimination — establishing natriuretic peptides as forensic biomarkers for cardiac function assessment at death.","whyItMatters":"Relevant for natriuretic-peptides, cardiovascular.","specificNumbers":"","methodology":"cross-sectional study.","limitations":"See abstract."},{"rthcId":"RPEP-01310","title":"Giustina 2008 Gh Igf1 Axis Consensus","authors":"","year":2008,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01311","title":"Pollak 2008 Igf1 Cancer Biology","authors":"","year":2008,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01312","title":"Oxytocin shapes the neural circuitry of trust and trust adaptation in humans.","authors":"Baumgartner, Thomas; Heinrichs, Markus; Vonlanthen, Aline; Fischbacher, Urs; Fehr, Ernst","year":2008,"journal":"Neuron, 58(4), 639-50","doi":"10.1016/j.neuron.2008.04.009","pmid":"18498743","tags":["oxytocin","neuroprotection","cognitive-enhancement"],"studyType":"RCT","evidenceStrength":"strong","keyFinding":"Intranasal oxytocin in healthy men increased trust behavior AND prevented trust adaptation (trust reduction) after betrayal in a social investment game, shaping the neural circuitry of both trust formation and trust resilience — with implications for social anxiety and autism.","whyItMatters":"Relevant for oxytocin, neuroprotection, cognitive-enhancement.","specificNumbers":"","methodology":"RCT study.","limitations":"See abstract."},{"rthcId":"RPEP-01313","title":"Vagal and hormonal gut-brain communication: from satiation to satisfaction.","authors":"Berthoud, H-R","year":2008,"journal":"Neurogastroenterology and motility, 20 Suppl 1(0 1), 64-72","doi":"10.1111/j.1365-2982.2008.01104.x","pmid":"18402643","tags":["neuropeptides","glp-1","weight-loss"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Post-meal fullness involves two phases: satiation (meal termination via vagal mechanoreception + CCK) and sustained satisfaction (inter-meal fullness via GLP-1, PYY, insulin, leptin) — distinguishing the immediate fullness signal from prolonged appetite suppression for targeted drug development.","whyItMatters":"Relevant for neuropeptides, glp-1, weight-loss.","specificNumbers":"","methodology":"review study.","limitations":"See abstract."},{"rthcId":"RPEP-01314","title":"Control of hormonal stress reactivity by the endogenous opioid system.","authors":"Bilkei-Gorzo, Andras; Racz, Ildiko; Michel, Kerstin; Mauer, Daniela; Zimmer, Anne; Klingmüller, Dietrich; Zimmer, Andreas","year":2008,"journal":"Psychoneuroendocrinology, 33(4), 425-36","doi":"10.1016/j.psyneuen.2007.12.010","pmid":"18280051","tags":["opioid-peptides","neuropeptides","anxiety-mood"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Endogenous opioid peptides regulate HPA axis stress reactivity through hypothalamic CRF and ACTH modulation, with opioid system disruption producing altered cortisol responses — explaining stress hormone dysregulation in chronic pain, addiction, and stress disorders.","whyItMatters":"Relevant for opioid-peptides, neuropeptides, anxiety-mood.","specificNumbers":"","methodology":"animal-study study.","limitations":"See abstract."},{"rthcId":"RPEP-01315","title":"Ghrelin control of GH secretion and feeding behaviour: the role of the GHS-R1a receptor studied in vivo and in vitro using novel non-peptide ligands.","authors":"Bresciani, E; Tamiazzo, L; Torsello, A; Bulgarelli, I; Rapetti, D; Caporali, S; Perrissoud, D; Moulin, A; Fehrentz, J A; Martinez, J; Locatelli, V","year":2008,"journal":"Eating and weight disorders : EWD, 13(3), e67-74","doi":null,"pmid":"19011367","tags":["ghrp","weight-loss","receptor-signaling"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"GHS-R1a pharmacological tools (agonists, antagonists, inverse agonists) revealed the receptor controls both GH secretion and feeding behavior, with receptor modification studies suggesting these functions may be partially separable for therapeutic benefit.","whyItMatters":"Relevant for ghrp, weight-loss, receptor-signaling.","specificNumbers":"","methodology":"review study.","limitations":"See abstract."},{"rthcId":"RPEP-01316","title":"GLP-1 receptor signaling: effects on pancreatic beta-cell proliferation and survival.","authors":"Buteau, J","year":2008,"journal":"Diabetes & metabolism, 34 Suppl 2, S73-7","doi":"10.1016/S1262-3636(08)73398-6","pmid":"18640589","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01317","title":"In vitro and in vivo wound healing-promoting activities of human cathelicidin LL-37.","authors":"Carretero, Marta; Escámez, María J; García, Marta; Duarte, Blanca; Holguín, Almudena; Retamosa, Luisa; Jorcano, Jose L; Río, Marcela Del; Larcher, Fernando","year":2008,"journal":"The Journal of investigative dermatology, 128(1), 223-36","doi":null,"pmid":"17805349","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"LL-37 activated migration of HaCaT human keratinocytes through multiple mechanisms: phenotypic changes in actin dynamics, increased tyrosine phosphorylation of focal adhesion kinase (FAK) and paxillin, induction of Snail and Slug transcription factors (associated with cell motility), activation of matrix metalloproteinases, and engagement of MAPK and PI3K/Akt signaling pathways.\n\nThese effects were mediated through both EGFR transactivation and induction of the FPRL-1 G-protein-coupled receptor. In vivo, adenoviral delivery of LL-37 to excisional wounds in ob/ob diabetic mice significantly improved re-epithelialization and granulation tissue formation — demonstrating that LL-37's wound healing benefits translate from cell culture to a clinically relevant impaired-healing animal model.","whyItMatters":"Chronic non-healing wounds — particularly diabetic ulcers — affect millions of people worldwide and are a leading cause of amputation. Current wound treatments are often inadequate. LL-37's unique dual action as both an antimicrobial agent (fighting wound infections) and a wound healing promoter (stimulating skin cell migration and tissue repair) makes it an exceptionally promising therapeutic candidate. The fact that it worked in diabetic mice, which have the most challenging healing environment, is particularly encouraging.","specificNumbers":"","methodology":"In vitro experiments used HaCaT human keratinocytes to characterize LL-37's effects on cell migration, actin dynamics, focal adhesion signaling, transcription factor expression, metalloproteinase activation, and signaling pathway engagement (MAPK, PI3K/Akt, EGFR, FPRL-1). In vivo experiments used adenoviral transfer to deliver LL-37 to excisional wounds in ob/ob mice (a model of diabetic impaired wound healing). Wound healing was assessed by measuring re-epithelialization and granulation tissue formation.","limitations":"The in vitro work used an immortalized keratinocyte cell line (HaCaT) which may not fully represent primary human skin cells. The in vivo delivery used adenoviral gene transfer, which is not a practical clinical delivery method for routine wound care. The ob/ob mouse model, while useful for studying impaired healing, has a specific genetic obesity that differs from most human diabetic wounds. The study did not assess long-term wound outcomes or scar quality. The multiple signaling pathways identified may not all contribute equally to the healing effect in vivo."},{"rthcId":"RPEP-01318","title":"Growth hormone-releasing hormone as an agonist of the ghrelin receptor GHS-R1a.","authors":"Casanueva, Felipe F; Camiña, Jesus P; Carreira, Marcos C; Pazos, Yolanda; Varga, Jozsef L; Schally, Andrew V","year":2008,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 105(51), 20452-7","doi":"10.1073/pnas.0811680106","pmid":"19088192","tags":["ghrp","cjc-1295","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"GHRH demonstrated agonist activity at the GHS-R1a (ghrelin receptor) at physiologically relevant concentrations, revealing previously unknown cross-talk between the GHRH and ghrelin receptor systems — explaining some synergistic GH-releasing effects.","whyItMatters":"Relevant for ghrp, cjc-1295, receptor-signaling.","specificNumbers":"","methodology":"in-vitro study.","limitations":"See abstract."},{"rthcId":"RPEP-01319","title":"The role of apelin in cardiovascular function and heart failure.","authors":"Chandrasekaran, Badrinathan; Dar, Owais; McDonagh, Theresa","year":2008,"journal":"European journal of heart failure, 10(8), 725-32","doi":"10.1016/j.ejheart.2008.06.002","pmid":"18583184","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01320","title":"N-methylation of peptides: a new perspective in medicinal chemistry.","authors":"Chatterjee, Jayanta; Gilon, Chaim; Hoffman, Amnon; Kessler, Horst","year":2008,"journal":"Accounts of chemical research, 41(10), 1331-42","doi":"10.1021/ar8000603","pmid":"18636716","tags":["peptide-design","bioavailability","cyclic-peptides"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"N-methylation of peptide backbone amides improves oral bioavailability, proteolytic stability, membrane permeability, and conformational rigidity — the key chemical modification enabling oral peptide drugs, validated by cyclosporine and being applied to new therapeutic peptides.","whyItMatters":"Relevant for peptide-design, bioavailability, cyclic-peptides.","specificNumbers":"","methodology":"review study.","limitations":"See abstract."},{"rthcId":"RPEP-01321","title":"Incorporation of a matrix metalloproteinase-sensitive substrate into self-assembling peptides - a model for biofunctional scaffolds.","authors":"Chau, Ying; Luo, Ying; Cheung, Alex C Y; Nagai, Yusuke; Zhang, Shuguang; Kobler, James B; Zeitels, Steven M; Langer, Robert","year":2008,"journal":"Biomaterials, 29(11), 1713-9","doi":"10.1016/j.biomaterials.2007.11.046","pmid":"18192002","tags":["peptide-design","peptide-delivery"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Self-assembling peptide hydrogels incorporating matrix metalloproteinase (MMP)-sensitive substrate sequences degraded in response to cell-secreted MMPs during tissue repair, creating enzyme-responsive smart scaffolds that adapt to the wound healing environment.","whyItMatters":"Relevant for peptide-design, peptide-delivery.","specificNumbers":"","methodology":"in-vitro study.","limitations":"See abstract."},{"rthcId":"RPEP-01322","title":"Cloning and expression of antibacterial goat lactoferricin from Escherichia coli AD494(DE3)pLysS expression system.","authors":"Chen, Gen-Hung; Yin, Li-Jung; Chiang, I-Hua; Jiang, Shann-Tzong","year":2008,"journal":"Journal of food protection, 71(12), 2523-5","doi":null,"pmid":"19244908","tags":["antimicrobial-peptides","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Goat lactoferricin cloned and expressed in E. coli AD494(DE3)pLysS with retained antibacterial activity against test organisms, expanding the recombinant lactoferricin production to a third species source.","whyItMatters":"Relevant for antimicrobial-peptides, peptide-design.","specificNumbers":"","methodology":"in-vitro study.","limitations":"See abstract."},{"rthcId":"RPEP-01323","title":"Expression and analysis of thymosin alpha1 concatemer in Escherichia coli.","authors":"Chen, Yuhui; Zhao, Lingxia; Shen, Guoan; Cui, Lijie; Ren, Weiwei; Zhang, Hui; Qian, Hongmei; Tang, Kexuan","year":2008,"journal":"Biotechnology and applied biochemistry, 49(Pt 1), 51-6","doi":null,"pmid":"17523920","tags":["thymosin-alpha-1","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Thymosin alpha-1 concatemer expression in E. coli produced multiple peptide copies per fusion protein, with enzymatic cleavage releasing biologically active thymosin alpha-1 — a high-yield manufacturing strategy for this clinical peptide drug.","whyItMatters":"Relevant for thymosin-alpha-1, peptide-design.","specificNumbers":"","methodology":"in-vitro study.","limitations":"See abstract."},{"rthcId":"RPEP-01324","title":"24-Week study on the use of collagen hydrolysate as a dietary supplement in athletes with activity-related joint pain.","authors":"Clark, Kristine L; Sebastianelli, Wayne; Flechsenhar, Klaus R; Aukermann, Douglas F; Meza, Felix; Millard, Roberta L; Deitch, John R; Sherbondy, Paul S; Albert, Ann","year":2008,"journal":"Current medical research and opinion, 24(5), 1485-96","doi":null,"pmid":"18416885","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01325","title":"GPR54 and kisspeptins.","authors":"Colledge, W H","year":2008,"journal":"Results and problems in cell differentiation, 46, 117-43","doi":"10.1007/400_2007_050","pmid":"18193176","tags":["neuropeptides","fertility","receptor-signaling"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Kisspeptins activate GPR54 receptor to control GnRH neuron firing, serving as the essential gatekeeper for puberty onset and adult fertility — GPR54 mutations cause both absent puberty (hypogonadotropic hypogonadism) and infertility, establishing kisspeptin as the master reproductive switch.","whyItMatters":"Relevant for neuropeptides, fertility, receptor-signaling.","specificNumbers":"","methodology":"review study.","limitations":"See abstract."},{"rthcId":"RPEP-01326","title":"Peptide impurities in commercial synthetic peptides and their implications for vaccine trial assessment.","authors":"Currier, Jeffrey R; Galley, Lynee M; Wenschuh, Holger; Morafo, Vivian; Ratto-Kim, Silvia; Gray, Clive M; Maboko, Leonard; Hoelscher, Michael; Marovich, Mary A; Cox, Josephine H","year":2008,"journal":"Clinical and vaccine immunology : CVI, 15(2), 267-76","doi":null,"pmid":"18077621","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Peptide library sets designed for HIV vaccine immune response testing, obtained from two independent custom peptide suppliers, contained contaminating peptides capable of generating false-positive results mimicking antigen-specific CD8+ T-cell responses.\n\nDetailed investigation revealed that an HIV-1 peptide was contaminated with approximately 1% by weight of a human cytomegalovirus (HCMV) peptide commonly used in cellular immunology research. Because HCMV infection is widespread in the population, this contamination triggered genuine but irrelevant T-cell responses that appeared to be HIV-specific. The false positives were consistent enough to mimic real vaccine-induced responses, which could have led to incorrect conclusions about vaccine efficacy.","whyItMatters":"Vaccine clinical trials rely on immune assays that use synthetic peptides to determine whether a vaccine works. If those peptides are contaminated, the trial could wrongly conclude a vaccine is effective. This study exposed a systemic quality problem in commercial peptide manufacturing that could affect any clinical trial using peptide-based immune assays — not just HIV vaccine studies.","specificNumbers":"","methodology":"Researchers analyzed T-cell assay results from HIV peptide library stimulation experiments and noticed suspicious CD8+ T-cell responses. They investigated the responding T-cell frequency and HLA restriction patterns, which pointed to a non-HIV peptide as the trigger. Analytical characterization (likely mass spectrometry) of the original peptide stock confirmed the presence of the HCMV contaminant. The team then developed a proposed biological quality assurance/quality control protocol to supplement standard biochemical testing.","limitations":"The study identified contamination in peptide sets from two suppliers but did not survey the broader commercial peptide manufacturing landscape. The frequency of this type of cross-contamination across the industry remains unknown. The proposed QA/QC protocols add cost and complexity to already expensive clinical trial workflows."},{"rthcId":"RPEP-01327","title":"PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation.","authors":"Dalmasso, Guillaume; Charrier-Hisamuddin, Laetitia; Nguyen, Hang Thi Thu; Yan, Yutao; Sitaraman, Shanthi; Merlin, Didier","year":2008,"journal":"Gastroenterology, 134(1), 166-78","doi":"10.1053/j.gastro.2007.10.026","pmid":"18061177","tags":["neuropeptides","inflammation-immunology"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"KPV (Lys-Pro-Val) enters intestinal epithelial cells and immune cells — including macrophages, T cells, and B cells — via the PepT1 peptide transporter. Once inside, KPV inhibited NF-kappaB activation and reduced IL-8 secretion in cells exposed to TNF-alpha. When PepT1 was silenced with siRNA, these anti-inflammatory effects were abolished.\n\nIn live mice, oral KPV reduced inflammation in both DSS-induced and TNBS-induced colitis models, as shown by decreased proinflammatory cytokine expression. Critically, PepT1 knockout mice showed no benefit from KPV, confirming that PepT1 is required for the peptide's anti-inflammatory action. This overturns the prior assumption that KPV works through melanocortin receptors.","whyItMatters":"Before this study, researchers assumed KPV worked the same way as its parent hormone alpha-MSH — through melanocortin receptors on cell surfaces. This paper rewrote that understanding by showing KPV actually needs to get inside the cell via PepT1 to work. That distinction matters enormously for drug development because PepT1 is the same transporter the gut uses to absorb dietary protein fragments, meaning KPV could potentially work as a simple oral medication rather than requiring injection — a major practical advantage for treating inflammatory bowel disease.","specificNumbers":"NF-kappaB inhibition; IL-8 reduction; anti-inflammatory in DSS and TNBS colitis; PepT1-mediated uptake","methodology":"The researchers used a combination of cell culture and animal experiments. In the lab, they confirmed PepT1 expression in intestinal epithelial cells (Caco2-BBE line) and immune cells, then measured KPV uptake, NF-kappaB activation, and IL-8 secretion. They used siRNA to silence PepT1 and verify it was essential. In mice, they induced colitis using two standard chemical models (DSS and TNBS) and tested oral KPV in both normal mice and PepT1 knockout mice to confirm the transporter's role.","limitations":"The in vivo experiments were conducted entirely in mice, whose gut physiology differs from humans. PepT1 knockout mice may have altered baseline gut function that could confound results. The study did not test specific doses or establish a dose-response curve for oral KPV. No human data were generated, and the chemical colitis models used (DSS and TNBS) don't perfectly replicate human IBD."},{"rthcId":"RPEP-01328","title":"Lunasin: a novel cancer preventive seed peptide that modifies chromatin.","authors":"de Lumen, Ben O","year":2008,"journal":"Journal of AOAC International, 91(4), 932-5","doi":null,"pmid":"18727555","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01329","title":"Emergence of ghrelin as a treatment for cachexia syndromes.","authors":"DeBoer, Mark Daniel","year":2008,"journal":"Nutrition (Burbank, Los Angeles County, Calif.), 24(9), 806-14","doi":"10.1016/j.nut.2008.06.013","pmid":"18725076","tags":["ghrp","cancer","weight-loss"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Ghrelin addresses cancer cachexia through triple mechanism: appetite stimulation (reversing anorexia), GH/IGF-1-mediated anabolism (opposing muscle wasting), and anti-inflammatory effects (countering inflammatory cytokine-driven catabolism) — emerging as the most comprehensive cachexia therapy.","whyItMatters":"Relevant for ghrp, cancer, weight-loss.","specificNumbers":"","methodology":"review study.","limitations":"See abstract."},{"rthcId":"RPEP-01330","title":"Anti-inflammatory neuropeptides: a new class of endogenous immunoregulatory agents.","authors":"Delgado, Mario; Ganea, Doina","year":2008,"journal":"Brain, behavior, and immunity, 22(8), 1146-51","doi":"10.1016/j.bbi.2008.06.001","pmid":"18598752","tags":["neuropeptides","inflammation","immune-function"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Anti-inflammatory neuropeptides (VIP, PACAP, alpha-MSH/KPV, CGRP, cortistatin) constitute an endogenous immunoregulatory system: generating regulatory T-cells, suppressing pathogenic Th1/Th17 responses, and promoting inflammation resolution — nature's own anti-inflammatory drug class.","whyItMatters":"Relevant for neuropeptides, inflammation, immune-function.","specificNumbers":"","methodology":"review study.","limitations":"See abstract."},{"rthcId":"RPEP-01331","title":"Genetic association of vasoactive intestinal peptide receptor with rheumatoid arthritis: altered expression and signal in immune cells.","authors":"Delgado, Mario; Robledo, Gema; Rueda, Blanca; Varela, Nieves; O'Valle, Francisco; Hernandez-Cortes, Pedro; Caro, Marta; Orozco, Gisela; Gonzalez-Rey, Elena; Martin, Javier","year":2008,"journal":"Arthritis and rheumatism, 58(4), 1010-9","doi":"10.1002/art.23482","pmid":"18383379","tags":["neuropeptides","inflammation","immune-function"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"VPAC1 receptor gene polymorphisms were associated with RA susceptibility, with RA patients showing altered VIP receptor expression and signaling — providing genetic evidence linking the neuropeptide anti-inflammatory system to autoimmune disease pathogenesis.","whyItMatters":"Relevant for neuropeptides, inflammation, immune-function.","specificNumbers":"","methodology":"clinical-trial study.","limitations":"See abstract."},{"rthcId":"RPEP-01332","title":"In vivo delivery of lentiviral vectors expressing vasoactive intestinal peptide complementary DNA as gene therapy for collagen-induced arthritis.","authors":"Delgado, Mario; Toscano, Miguel G; Benabdellah, Karim; Cobo, Marien; O'Valle, Francisco; Gonzalez-Rey, Elena; Martín, Francisco","year":2008,"journal":"Arthritis and rheumatism, 58(4), 1026-37","doi":"10.1002/art.23283","pmid":"18383372","tags":["neuropeptides","inflammation","immune-function"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Lentiviral VIP gene delivery to arthritic joints reduced inflammation, cartilage destruction, and bone erosion in collagen-induced arthritis mice — demonstrating neuropeptide gene therapy as a viable approach for local treatment of autoimmune joint disease.","whyItMatters":"Relevant for neuropeptides, inflammation, immune-function.","specificNumbers":"","methodology":"animal-study study.","limitations":"See abstract."},{"rthcId":"RPEP-01333","title":"Up-regulation of high voltage-activated Ca(2+) channels in GC somatotropes after long-term exposure to ghrelin and growth hormone releasing peptide-6.","authors":"Dominguez, Belisario; Avila, Traudy; Flores-Hernandez, Jorge; Lopez-Lopez, Gustavo; Martinez-Rodriguez, Herminia; Felix, Ricardo; Monjaraz, Eduardo","year":2008,"journal":"Cellular and molecular neurobiology, 28(6), 819-31","doi":"10.1007/s10571-007-9234-1","pmid":"18259854","tags":["ghrp","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Chronic ghrelin/GHRP exposure upregulated L-type and T-type high-voltage calcium channels in GC somatotrophs, enhancing calcium-dependent GH exocytosis capacity — a mechanism for sustained or increasing GH response during chronic secretagogue treatment.","whyItMatters":"Relevant for ghrp, receptor-signaling.","specificNumbers":"","methodology":"in-vitro study.","limitations":"See abstract."},{"rthcId":"RPEP-01334","title":"Identification of amino acids essential for the antiangiogenic activity of tumstatin and its use in combination antitumor activity.","authors":"Eikesdal, Hans Petter; Sugimoto, Hikaru; Birrane, Gabriel; Maeshima, Yohei; Cooke, Vesselina G; Kieran, Mark; Kalluri, Raghu","year":2008,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 105(39), 15040-5","doi":"10.1073/pnas.0807055105","pmid":"18818312","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Researchers identified three specific amino acids — leucine (L), valine (V), and aspartic acid (D) — as essential for the anti-angiogenic activity of tumstatin, a peptide derived from collagen type IV that inhibits blood vessel growth in tumors. A 25-amino acid fragment of tumstatin, when administered systemically, inhibited tumor growth and angiogenesis in mice. The peptide binds specifically to αvβ3 integrin on proliferating endothelial cells and localizes to tumor blood vessels in vivo. When combined with bevacizumab (the anti-VEGF antibody), the tumstatin peptide showed significantly improved anti-tumor efficacy against human renal cell carcinoma xenografts compared to either agent alone.","whyItMatters":"Tumors need to grow new blood vessels (angiogenesis) to survive and expand. This study pinpoints the exact amino acids that make the tumstatin peptide work as a natural angiogenesis blocker, and shows that combining it with bevacizumab — an existing cancer drug — produces better results than either treatment alone. This opens the door to peptide-antibody combination therapies that attack tumor blood supply through two different mechanisms simultaneously.","specificNumbers":"","methodology":"The study used site-directed mutagenesis to identify essential amino acids in the tumstatin peptide. Binding to αvβ3 integrin was confirmed on proliferating endothelial cells. In vivo anti-tumor activity was tested by systemic administration in mice bearing human renal cell carcinoma xenografts. 3D molecular modeling identified the putative binding interface on αvβ3 integrin. Combination therapy experiments compared tumstatin peptide alone, bevacizumab alone, and the combination against renal cell carcinoma xenografts.","limitations":"All in vivo experiments used mouse xenograft models with human tumor cells, which may not fully replicate human tumor biology. The tumstatin peptide's pharmacokinetics (half-life, bioavailability) in humans are unknown. Combination therapy results are from a single tumor type (renal cell carcinoma). No toxicity or safety data were reported."},{"rthcId":"RPEP-01335","title":"Effect of C-peptide on diabetic neuropathy in patients with type 1 diabetes.","authors":"Ekberg, Karin; Johansson, Bo-Lennart","year":2008,"journal":"Experimental diabetes research, 2008, 457912","doi":"10.1155/2008/457912","pmid":"18350117","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01336","title":"Orlistat inhibition of intestinal lipase acutely increases appetite and attenuates postprandial glucagon-like peptide-1-(7-36)-amide-1, cholecystokinin, and peptide YY concentrations.","authors":"Ellrichmann, Mark; Kapelle, Mario; Ritter, Peter R; Holst, Jens J; Herzig, Karl-Heinz; Schmidt, Wolfgang E; Schmitz, Frank; Meier, Juris J","year":2008,"journal":"The Journal of clinical endocrinology and metabolism, 93(10), 3995-8","doi":"10.1210/jc.2008-0924","pmid":"18647814","tags":["glp-1","neuropeptides","weight-loss"],"studyType":"RCT","evidenceStrength":"strong","keyFinding":"Orlistat inhibition of intestinal lipase acutely increased appetite and attenuated GLP-1/PYY satiety responses, proving that fat absorption (not just fat presence) is required for satiety hormone release — the gut must PROCESS fat to signal fullness.","whyItMatters":"Relevant for glp-1, neuropeptides, weight-loss.","specificNumbers":"","methodology":"RCT study.","limitations":"See abstract."},{"rthcId":"RPEP-01337","title":"The use of desmopressin in von Willebrand disease: the experience of the first 30 years (1977-2007).","authors":"Federici, A B","year":2008,"journal":"Haemophilia : the official journal of the World Federation of Hemophilia, 14 Suppl 1, 5-14","doi":"10.1111/j.1365-2516.2007.01610.x","pmid":"18173689","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01338","title":"Protein hydrolysates induce CCK release from enteroendocrine cells and act as partial agonists of the CCK1 receptor.","authors":"Foltz, Martin; Ansems, Patrick; Schwarz, Jessica; Tasker, Maria C; Lourbakos, Afrodite; Gerhardt, Cindy C","year":2008,"journal":"Journal of agricultural and food chemistry, 56(3), 837-43","doi":"10.1021/jf072611h","pmid":"18211011","tags":["bioactive-food-peptides","neuropeptides","weight-loss"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Protein hydrolysates directly stimulated CCK secretion from STC-1 enteroendocrine cells and showed partial CCK1 receptor agonist activity, demonstrating dual mechanisms: dietary peptides both trigger satiety hormone release AND directly activate satiety receptors.","whyItMatters":"Relevant for bioactive-food-peptides, neuropeptides, weight-loss.","specificNumbers":"","methodology":"in-vitro study.","limitations":"See abstract."},{"rthcId":"RPEP-01339","title":"Modulation of ceramide metabolism in T-leukemia cell lines potentiates apoptosis induced by the cationic antimicrobial peptide bovine lactoferricin.","authors":"Furlong, Suzanne J; Ridgway, Neale D; Hoskin, David W","year":2008,"journal":"International journal of oncology, 32(3), 537-44","doi":null,"pmid":"18292930","tags":["antimicrobial-peptides","cancer"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Lactoferricin B induced leukemia cell apoptosis through ceramide accumulation, and modulating ceramide metabolism (glucocerebrosidase inhibition) potentiated the killing — identifying the ceramide death pathway as the molecular mechanism for this anticancer peptide.","whyItMatters":"Relevant for antimicrobial-peptides, cancer.","specificNumbers":"","methodology":"in-vitro study.","limitations":"See abstract."},{"rthcId":"RPEP-01340","title":"Self-assembling peptide amphiphile nanofibers as a scaffold for dental stem cells.","authors":"Galler, Kerstin M; Cavender, Adriana; Yuwono, Virany; Dong, He; Shi, Songtao; Schmalz, Gottfried; Hartgerink, Jeffrey D; D'Souza, Rena N","year":2008,"journal":"Tissue engineering. Part A, 14(12), 2051-8","doi":"10.1089/ten.tea.2007.0413","pmid":"18636949","tags":["peptide-design","peptide-delivery"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Peptide amphiphile nanofibers self-assembled into scaffolds supporting dental stem cell (DPSC) adhesion, proliferation, and odontogenic differentiation — validating self-assembling peptide biomaterials for injectable dental tissue regeneration applications.","whyItMatters":"Relevant for peptide-design, peptide-delivery.","specificNumbers":"","methodology":"in-vitro study.","limitations":"See abstract."},{"rthcId":"RPEP-01341","title":"Expression of thymosin alpha1-thymopentin fusion peptide in Pichia pastoris and its characterization.","authors":"Gao, Demin; Zhang, Xulong; Zhang, Jian; Cao, Jichao; Wang, Fengshan","year":2008,"journal":"Archives of pharmacal research, 31(11), 1471-6","doi":"10.1007/s12272-001-2132-z","pmid":"19023544","tags":["thymosin-alpha-1","peptide-design","immune-function"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Thymosin alpha-1-thymopentin fusion peptide expressed in P. pastoris retained both components' immunostimulatory activities, creating a dual-function immune peptide combining T-cell modulation (TA1) with thymocyte maturation (TP-5) in a single recombinant molecule.","whyItMatters":"Relevant for thymosin-alpha-1, peptide-design, immune-function.","specificNumbers":"","methodology":"in-vitro study.","limitations":"See abstract."},{"rthcId":"RPEP-01342","title":"Appetite-related gut peptides, ghrelin, PYY, and GLP-1 in obese women with and without binge eating disorder (BED).","authors":"Geliebter, Allan; Hashim, Sami A; Gluck, Marci E","year":2008,"journal":"Physiology & behavior, 94(5), 696-9","doi":"10.1016/j.physbeh.2008.04.013","pmid":"18534636","tags":["neuropeptides","glp-1","weight-loss","anxiety-mood"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"Obese women with BED showed distinct postprandial gut peptide profiles (altered ghrelin, PYY3-36, GLP-1) compared to non-binge obese controls, identifying BED-specific gut hormone dysfunction beyond general obesity-related appetite changes.","whyItMatters":"Relevant for neuropeptides, glp-1, weight-loss, anxiety-mood.","specificNumbers":"","methodology":"clinical-trial study.","limitations":"See abstract."},{"rthcId":"RPEP-01343","title":"B-type natriuretic peptide (BNP) and proBNP: role of emerging markers to guide therapy and determine prognosis in cardiovascular disorders.","authors":"Godkar, Darshan; Bachu, Kalyan; Dave, Bijal; Niranjan, Selva; Khanna, Ashok","year":2008,"journal":"American journal of therapeutics, 15(2), 150-6","doi":"10.1097/MJT.0b013e31815af96f","pmid":"18356635","tags":["natriuretic-peptides","cardiovascular"],"studyType":"review","evidenceStrength":"strong","keyFinding":"BNP and NT-proBNP serve dual clinical roles: guiding heart failure drug therapy (titration endpoints) and predicting cardiovascular outcomes (mortality, hospitalization risk) — established as essential biomarkers in evidence-based cardiovascular care.","whyItMatters":"Relevant for natriuretic-peptides, cardiovascular.","specificNumbers":"","methodology":"review study.","limitations":"See abstract."},{"rthcId":"RPEP-01344","title":"GH-releasing peptide-2 administration prevents liver inflammatory response in endotoxemia.","authors":"Granado, Miriam; Martín, Ana Isabel; López-Menduiña, María; López-Calderón, Asunción; Villanúa, M Angeles","year":2008,"journal":"American journal of physiology. Endocrinology and metabolism, 294(1), E131-41","doi":null,"pmid":"17986630","tags":["ghrp","inflammation","liver"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"GHRP-2 administration prevented endotoxin-induced liver inflammation in rats: reduced hepatic TNF-α, IL-1β, IL-6, and NF-κB activation — demonstrating direct anti-inflammatory hepatoprotection by GH secretagogues independent of GH release.","whyItMatters":"Relevant for ghrp, inflammation, liver.","specificNumbers":"","methodology":"animal-study study.","limitations":"See abstract."},{"rthcId":"RPEP-01345","title":"Lipid interactions of acylated tryptophan-methylated lactoferricin peptides by solid-state NMR.","authors":"Greathouse, Denise; Vostrikov, Vitaly; McClellan, Nicole; Chipollini, Juan; Lay, Jack; Liyanage, Rohana; Ladd, Taylor","year":2008,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 14(10), 1103-10","doi":"10.1002/psc.1047","pmid":"18523968","tags":["antimicrobial-peptides","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Solid-state NMR revealed acylated, tryptophan-methylated lactoferricin peptides inserted deeper into lipid bilayers with stronger membrane disruption, providing molecular-level explanation for how chemical modifications enhance antimicrobial potency.","whyItMatters":"Relevant for antimicrobial-peptides, peptide-design.","specificNumbers":"","methodology":"in-vitro study.","limitations":"See abstract."},{"rthcId":"RPEP-01346","title":"Design and microwave-assisted synthesis of novel macrocyclic peptides active at melanocortin receptors: discovery of potent and selective hMC5R receptor antagonists.","authors":"Grieco, Paolo; Cai, Minying; Liu, Lu; Mayorov, Alexander; Chandler, Kevin; Trivedi, Dev; Lin, Guangxin; Campiglia, Pietro; Novellino, Ettore; Hruby, Victor J","year":2008,"journal":"Journal of medicinal chemistry, 51(9), 2701-7","doi":"10.1021/jm701181n","pmid":"18412316","tags":["melanotan","pt-141","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Novel macrocyclic melanocortin peptides synthesized by microwave-assisted methods showed potent MC1R/MC4R activity, with the macrocyclic constraint improving receptor selectivity and metabolic stability — advancing circular peptide drugs for melanocortin receptor-mediated therapies.","whyItMatters":"Relevant for melanotan, pt-141, peptide-design.","specificNumbers":"","methodology":"in-vitro study.","limitations":"See abstract."},{"rthcId":"RPEP-01347","title":"The impact of postnatal environment on opioid peptides in young and adult male Wistar rats.","authors":"Gustafsson, Lisa; Oreland, Sadia; Hoffmann, Pernilla; Nylander, Ingrid","year":2008,"journal":"Neuropeptides, 42(2), 177-91","doi":null,"pmid":"18082882","tags":["opioid-peptides","neuropeptides","anxiety-mood"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Postnatal environment quality produced lasting changes in brain opioid peptide levels (dynorphin, enkephalin) across development into adulthood in Wistar rats, demonstrating enduring early-life programming of the opioid system that may predispose to later psychopathology.","whyItMatters":"Relevant for opioid-peptides, neuropeptides, anxiety-mood.","specificNumbers":"","methodology":"animal-study study.","limitations":"See abstract."},{"rthcId":"RPEP-01348","title":"Immunoregulatory properties of vasoactive intestinal peptide in human T cell subsets: implications for rheumatoid arthritis.","authors":"Gutiérrez-Cañas, Irene; Juarranz, Yasmina; Santiago, Begoña; Martínez, Carmen; Gomariz, Rosa P; Pablos, José Luis; Leceta, Javier","year":2008,"journal":"Brain, behavior, and immunity, 22(3), 312-7","doi":null,"pmid":"17951026","tags":["neuropeptides","inflammation","immune-function"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"VIP differentially modulated human T-cell subsets: suppressed CD4+ effector T-cell proliferation/activation while supporting CD4+CD25+ regulatory T-cell function and survival — directly applicable to restoring the effector/regulatory T-cell balance in rheumatoid arthritis.","whyItMatters":"Relevant for neuropeptides, inflammation, immune-function.","specificNumbers":"","methodology":"in-vitro study.","limitations":"See abstract."},{"rthcId":"RPEP-01349","title":"Growth hormone and insulin-like growth factor-I as an endocrine axis in Alzheimer's disease.","authors":"Gómez, José Manuel","year":2008,"journal":"Endocrine, metabolic & immune disorders drug targets, 8(2), 143-51","doi":null,"pmid":"18537700","tags":["hormone-optimization","neuroprotection","anti-aging"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"GH/IGF-1 axis decline correlates with Alzheimer's disease progression, with IGF-1 supporting neuronal survival, beta-amyloid clearance, and synaptic function — GH secretagogues that restore this axis may offer neuroprotective therapeutic benefit for dementia.","whyItMatters":"Relevant for hormone-optimization, neuroprotection, anti-aging.","specificNumbers":"","methodology":"review study.","limitations":"See abstract."},{"rthcId":"RPEP-01350","title":"Defensin susceptibility and colonization in the mouse model of AJ100, a polymyxin B-resistant, Brucella abortus RB51 isolate.","authors":"Halling, Shirley M; Jensen, Allen E; Olsen, Steven C","year":2008,"journal":"Current microbiology, 56(3), 274-8","doi":"10.1007/s00284-007-9074-8","pmid":"18214602","tags":["antimicrobial-peptides","infection"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Polymyxin B-resistant Brucella abortus showed modified defensin susceptibility and altered colonization in mice, demonstrating that antimicrobial peptide resistance affects bacterial fitness, virulence, and tissue tropism in vivo — not just simple survival.","whyItMatters":"Relevant for antimicrobial-peptides, infection.","specificNumbers":"","methodology":"animal-study study.","limitations":"See abstract."},{"rthcId":"RPEP-01351","title":"Spatial distribution of mineralized bone matrix produced by marrow mesenchymal stem cells in self-assembling peptide hydrogel scaffold.","authors":"Hamada, Kazunori; Hirose, Motohiro; Yamashita, Toshihiko; Ohgushi, Hajime","year":2008,"journal":"Journal of biomedical materials research. Part A, 84(1), 128-36","doi":null,"pmid":"17600333","tags":["cyclic-peptides","bone-joint","wound-healing"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Marrow mesenchymal stem cells in self-assembling peptide hydrogels produced spatially organized mineralized bone matrix resembling natural trabecular bone distribution, demonstrating peptide scaffolds can guide not just cell growth but organized bone tissue formation.","whyItMatters":"Relevant for cyclic-peptides, bone-joint, wound-healing.","specificNumbers":"","methodology":"in-vitro study.","limitations":"See abstract."},{"rthcId":"RPEP-01352","title":"Neuropeptides and social behaviour: effects of oxytocin and vasopressin in humans.","authors":"Heinrichs, Markus; Domes, Gregor","year":2008,"journal":"Progress in brain research, 170, 337-50","doi":"10.1016/S0079-6123(08)00428-7","pmid":"18655894","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01353","title":"Contemporary strategies for the stabilization of peptides in the alpha-helical conformation.","authors":"Henchey, Laura K; Jochim, Andrea L; Arora, Paramjit S","year":2008,"journal":"Current opinion in chemical biology, 12(6), 692-7","doi":"10.1016/j.cbpa.2008.08.019","pmid":"18793750","tags":["cyclic-peptides","peptide-design"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Contemporary helix stabilization strategies include hydrocarbon stapling, hydrogen bond surrogates, salt bridges, disulfide crosslinks, and unnatural amino acids — chemical approaches that lock therapeutic peptides into bioactive helical conformations for clinical development.","whyItMatters":"Relevant for cyclic-peptides, peptide-design.","specificNumbers":"","methodology":"review study.","limitations":"See abstract."},{"rthcId":"RPEP-01354","title":"Short linear cationic antimicrobial peptides: screening, optimizing, and prediction.","authors":"Hilpert, Kai; Fjell, Christopher D; Cherkasov, Artem","year":2008,"journal":"Methods in molecular biology (Clifton, N.J.), 494, 127-59","doi":"10.1007/978-1-59745-419-3_8","pmid":"18726572","tags":["antimicrobial-peptides","peptide-design","infection"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Short linear cationic antimicrobial peptides (≤25 residues) can be systematically screened, optimized through SAR rules (charge, hydrophobicity, amphipathicity), and computationally predicted for activity — a practical framework for antimicrobial peptide drug development.","whyItMatters":"Relevant for antimicrobial-peptides, peptide-design, infection.","specificNumbers":"","methodology":"review study.","limitations":"See abstract."},{"rthcId":"RPEP-01355","title":"Postprandial changes in gut regulatory peptides in gastric bypass patients.","authors":"Holdstock, C; Zethelius, B; Sundbom, M; Karlsson, F A; Edén Engström, B","year":2008,"journal":"International journal of obesity (2005), 32(11), 1640-6","doi":"10.1038/ijo.2008.157","pmid":"18794895","tags":["glp-1","neuropeptides","weight-loss"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"Postprandial GLP-1, PYY3-36, and other gut regulatory peptides dramatically increased following gastric bypass, with enhanced hormonal satiety signaling correlating with reduced appetite and caloric intake — hormonal reprogramming, not restriction, as the primary surgical mechanism.","whyItMatters":"Relevant for glp-1, neuropeptides, weight-loss.","specificNumbers":"","methodology":"clinical-trial study.","limitations":"See abstract."},{"rthcId":"RPEP-01356","title":"Cyclotides as natural anti-HIV agents.","authors":"Ireland, David C; Wang, Conan K L; Wilson, Jennifer A; Gustafson, Kirk R; Craik, David J","year":2008,"journal":"Biopolymers, 90(1), 51-60","doi":null,"pmid":"18008336","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01357","title":"Molecular genetic studies of the arginine vasopressin 1a receptor (AVPR1a) and the oxytocin receptor (OXTR) in human behaviour: from autism to altruism with some notes in between.","authors":"Israel, Salomon; Lerer, Elad; Shalev, Idan; Uzefovsky, Florina; Reibold, Mathias; Bachner-Melman, Rachel; Granot, Roni; Bornstein, Gary; Knafo, Ariel; Yirmiya, Nurit; Ebstein, Richard P","year":2008,"journal":"Progress in brain research, 170, 435-49","doi":"10.1016/S0079-6123(08)00434-2","pmid":"18655900","tags":["oxytocin","neuropeptides","anxiety-mood"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"AVPR1a and OXTR genetic polymorphisms are associated with human social behavior variation: autism spectrum features, pair-bonding patterns, empathy levels, and social anxiety — establishing the genetic basis for neuropeptide-mediated social behavior.","whyItMatters":"Relevant for oxytocin, neuropeptides, anxiety-mood.","specificNumbers":"","methodology":"review study.","limitations":"See abstract."},{"rthcId":"RPEP-01358","title":"Transport of micro-opioid receptor agonists and antagonist peptides across Caco-2 monolayer.","authors":"Iwan, Małgorzata; Jarmołowska, Beata; Bielikowicz, Krzysztof; Kostyra, Elzbieta; Kostyra, Henryk; Kaczmarski, Maciej","year":2008,"journal":"Peptides, 29(6), 1042-7","doi":"10.1016/j.peptides.2008.01.018","pmid":"18355944","tags":["opioid-peptides","bioactive-food-peptides","bioavailability"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Mu-opioid peptide agonists and antagonists showed variable Caco-2 monolayer permeability, with some achieving transcellular transport — assessing oral bioavailability potential and identifying which opioid peptide structures achieve gut barrier crossing.","whyItMatters":"Relevant for opioid-peptides, bioactive-food-peptides, bioavailability.","specificNumbers":"","methodology":"in-vitro study.","limitations":"See abstract."},{"rthcId":"RPEP-01359","title":"The influence of the eradication of Helicobacter pylori on gastric ghrelin, appetite, and body mass index in patients with peptic ulcer disease.","authors":"Jang, Eun Jeong; Park, Sang Woon; Park, Ju Sang; Park, Sang Jong; Hahm, Ki-Baik; Paik, So Ya; Sin, Mi Kyung; Lee, Eon Sook; Oh, Sang Woo; Park, Cheol Young; Baik, Hyun Wook","year":2008,"journal":"Journal of gastroenterology and hepatology, 23 Suppl 2, S278-85","doi":"10.1111/j.1440-1746.2008.05415.x","pmid":"19120912","tags":["neuropeptides","gut-healing"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"H. pylori eradication restored gastric ghrelin expression and increased circulating ghrelin levels, correlating with increased appetite and BMI gain — providing the hormonal mechanism for the weight gain commonly observed after successful H. pylori treatment.","whyItMatters":"Relevant for neuropeptides, gut-healing.","specificNumbers":"","methodology":"clinical-trial study.","limitations":"See abstract."},{"rthcId":"RPEP-01360","title":"Self-assembling peptide-polymer hydrogels designed from the coiled coil region of fibrin.","authors":"Jing, Peng; Rudra, Jai S; Herr, Andrew B; Collier, Joel H","year":2008,"journal":"Biomacromolecules, 9(9), 2438-46","doi":"10.1021/bm800459v","pmid":"18712921","tags":["cyclic-peptides","wound-healing","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Peptide-polymer hydrogels designed from fibrin's coiled-coil region self-assembled into scaffolds mimicking natural wound healing matrix, with tunable mechanical properties suitable for tissue engineering — bio-inspired design from the body's own clotting protein.","whyItMatters":"Relevant for cyclic-peptides, wound-healing, peptide-design.","specificNumbers":"","methodology":"in-vitro study.","limitations":"See abstract."},{"rthcId":"RPEP-01361","title":"Modulating the mechanical properties of self-assembled peptide hydrogels via native chemical ligation.","authors":"Jung, Jangwook P; Jones, Julia L; Cronier, Samantha A; Collier, Joel H","year":2008,"journal":"Biomaterials, 29(13), 2143-51","doi":"10.1016/j.biomaterials.2008.01.008","pmid":"18261790","tags":["cyclic-peptides","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Native chemical ligation crosslinking of self-assembling peptide hydrogels enabled tunable mechanical properties (stiffness, resilience), allowing scaffolds to match tissue-specific mechanical environments — precision biomaterial engineering for diverse tissue regeneration.","whyItMatters":"Relevant for cyclic-peptides, peptide-design.","specificNumbers":"","methodology":"in-vitro study.","limitations":"See abstract."},{"rthcId":"RPEP-01362","title":"Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease.","authors":"Kannengiesser, K; Maaser, C; Heidemann, J; Luegering, A; Ross, M; Brzoska, T; Böhm, M; Luger, T A; Domschke, W; Kucharzik, T","year":2008,"journal":"Peptides, 29(12), 2137-46","doi":"10.1016/j.peptides.2007.10.012","pmid":"18092346","tags":["neuropeptides","inflammation-immunology"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"In the DSS-colitis model, KPV treatment led to significantly earlier recovery and stronger body weight regain compared to controls (p<0.01). Inflammatory cell infiltration was significantly reduced (p<0.05). In the adoptive transfer model (a T cell-driven colitis that more closely mimics human IBD), KPV-treated mice had significantly lower clinical scores, less body weight loss, and lower grades of tissue inflammation on histology.\n\nIn vitro, KPV inhibited TNF-alpha-induced IL-8 secretion in intestinal epithelial cells, demonstrating a direct anti-inflammatory mechanism at the cellular level.","whyItMatters":"Inflammatory bowel disease (Crohn's and ulcerative colitis) affects millions of people, and current treatments often have significant side effects. KPV's anti-inflammatory effects in two mechanistically different colitis models — one driven by chemical injury, one by immune cells — suggests broad applicability. Its tiny size (just 3 amino acids) makes it potentially easier and cheaper to produce than full-length protein therapies.","specificNumbers":"Body weight regain P<0.01; inflammatory infiltrates P<0.05; lower clinical scores in adoptive transfer model","methodology":"Two murine colitis models were used: DSS-induced colitis (chemical injury model) and T cell adoptive transfer colitis (immune-mediated model). KPV was administered intraperitoneally. Outcomes measured included body weight changes, clinical scores, and histological assessment of tissue inflammation. In vitro experiments tested KPV's effect on TNF-alpha-induced IL-8 secretion in intestinal epithelial cells.","limitations":"Both models are murine (mouse), and results may not translate directly to human IBD. KPV was administered intraperitoneally (injected into the abdomen), not orally, so oral bioavailability wasn't tested. Specific dosing details and exact group sizes are not provided in the abstract. No human clinical trial data exists for KPV in IBD."},{"rthcId":"RPEP-01363","title":"Effect of protein, fat, carbohydrate and fibre on gastrointestinal peptide release in humans.","authors":"Karhunen, L J; Juvonen, K R; Huotari, A; Purhonen, A K; Herzig, K H","year":2008,"journal":"Regulatory peptides, 149(1-3), 70-8","doi":"10.1016/j.regpep.2007.10.008","pmid":"18456350","tags":["neuropeptides","glp-1","weight-loss"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Different macronutrients trigger distinct gut peptide profiles: protein produces the strongest and most diverse satiety peptide response (GLP-1, PYY, CCK); fat strongly triggers CCK/GLP-1; carbohydrate mainly GIP/insulin; fiber enhances GLP-1/PYY through fermentation — macronutrient-specific appetite pharmacology.","whyItMatters":"Relevant for neuropeptides, glp-1, weight-loss.","specificNumbers":"","methodology":"review study.","limitations":"See abstract."},{"rthcId":"RPEP-01364","title":"Hormone-based therapies in the regulation of fuel metabolism and body weight.","authors":"Kesty, Nicole C; Roth, Jonathan D; Maggs, David","year":2008,"journal":"Expert opinion on biological therapy, 8(11), 1733-47","doi":"10.1517/14712598.8.11.1733","pmid":"18847308","tags":["glp-1","neuropeptides","weight-loss","diabetes"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Hormone-based fuel metabolism drugs span GLP-1 agonists (semaglutide class), amylin analogs (pramlintide), PYY analogs, and ghrelin modulators for integrated obesity/diabetes treatment — exploiting endogenous regulatory peptide systems for superior metabolic control.","whyItMatters":"Relevant for glp-1, neuropeptides, weight-loss, diabetes.","specificNumbers":"","methodology":"review study.","limitations":"See abstract."},{"rthcId":"RPEP-01365","title":"Involvement of spinal Met-enkephalin in nicotine-induced antinociception in mice.","authors":"Kiguchi, Norikazu; Maeda, Takehiko; Tsuruga, Mie; Yamamoto, Akihiro; Yamamoto, Chizuko; Ozaki, Masanobu; Kishioka, Shiroh","year":2008,"journal":"Brain research, 1189, 70-7","doi":null,"pmid":"18048009","tags":["opioid-peptides","neuropeptides","pain"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Nicotine antinociception involved spinal met-enkephalin release confirmed by intrathecal anti-met-enkephalin antibody blocking, extending the drug-endogenous opioid amplification mechanism to nicotine — explaining some of smoking's pain-modifying effects.","whyItMatters":"Relevant for opioid-peptides, neuropeptides, pain.","specificNumbers":"","methodology":"animal-study study.","limitations":"See abstract."},{"rthcId":"RPEP-01366","title":"Pentadecapeptide BPC 157, in clinical trials as a therapy for inflammatory bowel disease (PL14736), is effective in the healing of colocutaneous fistulas in rats: role of the nitric oxide-system.","authors":"Klicek, Robert; Sever, Marko; Radic, Bozo; Drmic, Domagoj; Kocman, Ivan; Zoricic, Ivan; Vuksic, Tihomir; Ivica, Mihovil; Barisic, Ivan; Ilic, Spomenko; Berkopic, Lidija; Vrcic, Hrvoje; Brcic, Luka; Blagaic, Alenka Boban; Coric, Marijana; Brcic, Iva; Rokotov, Dinko Stancic; Anic, Tomislav; Seiwerth, Sven; Sikiric, Predrag","year":2008,"journal":"Journal of pharmacological sciences, 108(1), 7-17","doi":null,"pmid":"18818478","tags":["bpc-157","gut-healing","wound-healing"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"BPC-157 (PL14736, in IBD clinical trials) effectively healed various types of healing-impaired wounds in rats including steroid-impaired, denervated, and complex soft tissue injuries — expanding its clinical development potential from IBD to wound healing indications.","whyItMatters":"Relevant for bpc-157, gut-healing, wound-healing.","specificNumbers":"","methodology":"animal-study study.","limitations":"See abstract."},{"rthcId":"RPEP-01367","title":"Structure and function of ghrelin.","authors":"Kojima, Masayasu; Kangawa, Kenji","year":2008,"journal":"Results and problems in cell differentiation, 46, 89-115","doi":"10.1007/400_2007_049","pmid":"18193177","tags":["neuropeptides","hormone-optimization","weight-loss"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Ghrelin's complete structural-functional profile: 28 amino acids with essential octanoyl modification on Ser3, GHS-R1a receptor activation, widespread tissue expression, and validated functions in GH release, appetite, energy homeostasis, and cardiovascular protection.","whyItMatters":"Relevant for neuropeptides, hormone-optimization, weight-loss.","specificNumbers":"","methodology":"review study.","limitations":"See abstract."},{"rthcId":"RPEP-01368","title":"Chronic psychosocial stress affects corticotropin-releasing factor in the paraventricular nucleus and central extended amygdala as well as urocortin 1 in the non-preganglionic Edinger-Westphal nucleus of the tree shrew.","authors":"Kozicz, T; Bordewin, L A P; Czéh, B; Fuchs, E; Roubos, E W","year":2008,"journal":"Psychoneuroendocrinology, 33(6), 741-54","doi":"10.1016/j.psyneuen.2008.02.012","pmid":"18394812","tags":["neuropeptides","anxiety-mood"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Chronic psychosocial stress produced CRF alterations in the PVN and central amygdala correlating with increased anxiety-like behavior, mapping how chronic social stress reprograms the brain's CRF stress system to produce persistent anxiety.","whyItMatters":"Relevant for neuropeptides, anxiety-mood.","specificNumbers":"","methodology":"animal-study study.","limitations":"See abstract."},{"rthcId":"RPEP-01369","title":"Plasma concentrations of matrix metalloproteinase-2, tissue inhibitor of metalloproteinase-1 and osteopontin reflect severity of heart failure in DOCA-salt hypertensive rat.","authors":"Kramer, Frank; Sandner, Peter; Klein, Martina; Krahn, Thomas","year":2008,"journal":"Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals, 13(3), 270-81","doi":"10.1080/13547500801903123","pmid":"18415800","tags":["natriuretic-peptides","cardiovascular"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Plasma MMP-2, TIMP-1, and osteopontin correlated with BNP levels and heart failure severity, providing remodeling biomarkers complementing natriuretic peptides — matrix markers capture the structural damage that peptide markers capture functionally.","whyItMatters":"Relevant for natriuretic-peptides, cardiovascular.","specificNumbers":"","methodology":"animal-study study.","limitations":"See abstract."},{"rthcId":"RPEP-01370","title":"New drugs for type 2 diabetes mellitus: what is their place in therapy?","authors":"Krentz, Andrew J; Patel, Mayank B; Bailey, Clifford J","year":2008,"journal":"Drugs, 68(15), 2131-62","doi":null,"pmid":"18840004","tags":["glp-1","diabetes","semaglutide","tirzepatide"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"New diabetes drugs include GLP-1 agonists (exenatide, liraglutide: injectable, weight loss, low hypo risk), DPP-4 inhibitors (sitagliptin, vildagliptin: oral, weight neutral), and amylin analog (pramlintide) — peptide-based drugs transforming type 2 diabetes treatment.","whyItMatters":"Relevant for glp-1, diabetes, semaglutide, tirzepatide.","specificNumbers":"","methodology":"review study.","limitations":"See abstract."},{"rthcId":"RPEP-01371","title":"Modulation of early functional recovery of Achilles tendon to bone unit after transection by BPC 157 and methylprednisolone.","authors":"Krivic, A; Majerovic, M; Jelic, I; Seiwerth, S; Sikiric, P","year":2008,"journal":"Inflammation research : official journal of the European Histamine Research Society ... [et al.], 57(5), 205-10","doi":"10.1007/s00011-007-7056-8","pmid":"18594781","tags":["bpc-157","muscle-recovery","bone-joint"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"BPC-157 improved early functional recovery (load-to-failure, stiffness) of transected Achilles tendon-to-bone unit, with efficacy maintained during concurrent methylprednisolone — confirming dual tendon-healing and steroid-impairment-overcoming capabilities.","whyItMatters":"Relevant for bpc-157, muscle-recovery, bone-joint.","specificNumbers":"","methodology":"animal-study study.","limitations":"See abstract."},{"rthcId":"RPEP-01372","title":"Effects of acute ethanol on opioid peptide release in the central amygdala: an in vivo microdialysis study.","authors":"Lam, Minh P; Marinelli, Peter W; Bai, Li; Gianoulakis, Christina","year":2008,"journal":"Psychopharmacology, 201(2), 261-71","doi":"10.1007/s00213-008-1267-8","pmid":"18688603","tags":["opioid-peptides","neuropeptides","addiction"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"In-vivo microdialysis showed acute ethanol directly triggered beta-endorphin and met-enkephalin release in the central amygdala, providing real-time evidence for alcohol's emotional/anxiolytic effects through local opioid peptide release in the brain's fear center.","whyItMatters":"Relevant for opioid-peptides, neuropeptides, addiction.","specificNumbers":"","methodology":"animal-study study.","limitations":"See abstract."},{"rthcId":"RPEP-01373","title":"Association of pro-ghrelin and GHS-R1A gene polymorphisms and haplotypes with heavy alcohol use and body mass.","authors":"Landgren, Sara; Jerlhag, Elisabet; Zetterberg, Henrik; Gonzalez-Quintela, Arturo; Campos, Joaquin; Olofsson, Ulrica; Nilsson, Staffan; Blennow, Kaj; Engel, Jörgen A","year":2008,"journal":"Alcoholism, clinical and experimental research, 32(12), 2054-61","doi":"10.1111/j.1530-0277.2008.00793.x","pmid":"18828808","tags":["neuropeptides","addiction","hormone-optimization"],"studyType":"cross-sectional","evidenceStrength":"preliminary","keyFinding":"Pro-ghrelin and GHS-R1A gene polymorphisms and haplotypes were associated with heavy alcohol use and BMI in humans, providing genetic evidence linking the ghrelin system to both alcohol addiction vulnerability and body weight regulation.","whyItMatters":"Relevant for neuropeptides, addiction, hormone-optimization.","specificNumbers":"","methodology":"cross-sectional study.","limitations":"See abstract."},{"rthcId":"RPEP-01374","title":"Novel melanocortin 4 receptor gene mutations in severely obese children.","authors":"Lee, Yung Seng; Poh, Larry Kok Seng; Kek, Betty Lay Kee; Loke, Kah Yin","year":2008,"journal":"Clinical endocrinology, 68(4), 529-35","doi":null,"pmid":"17941900","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01375","title":"Inhalation of vasoactive intestinal peptide in pulmonary hypertension.","authors":"Leuchte, H H; Baezner, C; Baumgartner, R A; Bevec, D; Bacher, G; Neurohr, C; Behr, J","year":2008,"journal":"The European respiratory journal, 32(5), 1289-94","doi":"10.1183/09031936.00050008","pmid":"18978135","tags":["vasoactive-intestinal-peptide","pulmonary-hypertension","cardiovascular"],"studyType":"Clinical Trial (Uncontrolled)","evidenceStrength":"Preliminary","keyFinding":"A single inhaled dose of aviptadil (100 μg), a synthetic form of vasoactive intestinal peptide (VIP), caused selective pulmonary vasodilation in patients with chronic pulmonary hypertension. The peptide improved stroke volume and mixed venous oxygen saturation — indicating reduced strain on the right ventricle — without affecting systemic blood pressure. Six of 20 patients (30%) achieved a clinically meaningful >20% reduction in pulmonary vascular resistance.\n\nIn patients with significant lung disease, aviptadil also tended to improve oxygenation. The effect was modest and temporary (as expected from a single dose), but no side effects were reported. The selective pulmonary vasodilation means the drug targeted the lung blood vessels specifically without dropping blood pressure throughout the rest of the body.","whyItMatters":"Pulmonary hypertension is a devastating condition where high pressure in the lung arteries forces the right side of the heart to work progressively harder until it fails. Current treatments help but don't cure the disease. VIP is naturally deficient in patients with idiopathic pulmonary arterial hypertension, making replacement therapy a logical approach. The fact that inhaled aviptadil selectively dilated lung vessels without systemic side effects is promising — inhaled delivery keeps the drug where it's needed most.","specificNumbers":"n=20 · single 100 μg inhaled dose · 6/20 (30%) achieved >20% PVR reduction · improved stroke volume · improved mixed venous O2 saturation · no systemic BP drop · zero side effects","methodology":"Open-label study in 20 patients with chronic pulmonary hypertension (9 PAH, 8 PH with lung disease, 3 chronic thromboembolic PH). During right-heart catheterization, patients inhaled a single 100 μg dose of aviptadil aerosol. Hemodynamic parameters (pulmonary vascular resistance, stroke volume, cardiac output) and blood gases (arterial and mixed venous oxygen saturation) were measured before and after inhalation.","limitations":"This was an uncontrolled, open-label study with no placebo group, so the effects could partly reflect the natural variability of hemodynamics during catheterization. The single-dose design only assessed acute effects — chronic dosing may produce different results. The 100 μg dose may have been suboptimal (the authors suggest higher doses should be tested). Only 20 patients were studied across three different PH subtypes, limiting subgroup analysis. The temporary nature of the effect means multiple daily doses would likely be needed for clinical use."},{"rthcId":"RPEP-01376","title":"(D)-2-tert-Butoxycarbonylamino-5,5-difluoro-5-phenyl-pentanoic acid: synthesis and incorporation into the growth hormone secretagogues.","authors":"Li, Jun; Chen, Stephanie Y; Murphy, Brian J; Flynn, Neil; Seethala, Ramakrishna; Slusarchyk, Dorothy; Yan, Mujing; Sleph, Paul; Zhang, Hongjian; Humphreys, William G; Ewing, William R; Robl, Jeffrey A; Gordon, David; Tino, Joseph A","year":2008,"journal":"Bioorganic & medicinal chemistry letters, 18(14), 4072-4","doi":"10.1016/j.bmcl.2008.05.100","pmid":"18554903","tags":["ghrp","peptide-design","hormone-optimization"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"A novel difluorophenylalanine analog was incorporated into GHRP, maintaining GHS-R activity while introducing fluorine-mediated metabolic stability improvements — demonstrating unnatural amino acid incorporation for enhancing GH secretagogue drug properties.","whyItMatters":"Relevant for ghrp, peptide-design, hormone-optimization.","specificNumbers":"","methodology":"in-vitro study.","limitations":"See abstract."},{"rthcId":"RPEP-01377","title":"(68)Ga-labeled multimeric RGD peptides for microPET imaging of integrin alpha(v)beta (3) expression.","authors":"Li, Zi-Bo; Chen, Kai; Chen, Xiaoyuan","year":2008,"journal":"European journal of nuclear medicine and molecular imaging, 35(6), 1100-8","doi":"10.1007/s00259-007-0692-y","pmid":"18204838","tags":["peptide-imaging"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"Gallium-68 labeled RGD peptides successfully imaged tumors in mice by targeting integrin αvβ3, a protein overexpressed on tumor blood vessels. Three versions were tested — single (RGD1), double (RGD2), and quadruple (RGD4) RGD peptide constructs. The dimeric version (68Ga-NOTA-RGD2) emerged as the best candidate, achieving 2.8% ID/g tumor uptake at 1 hour with favorable tumor-to-background ratios (4.4 tumor/muscle, 2.0 tumor/liver, 1.1 tumor/kidney).\n\nThe quadruple version (RGD4) had the highest tumor uptake but also accumulated heavily in the kidneys, making it less suitable for clinical use. All three constructs could be labeled with 68Ga within 10 minutes, a major practical advantage since 68Ga comes from a generator (no cyclotron needed).","whyItMatters":"Most PET tracers require a cyclotron — an expensive particle accelerator — to produce the radioactive isotope. Gallium-68 comes from a desktop generator, making PET imaging accessible to hospitals without cyclotrons. Combining this convenient isotope with tumor-targeting RGD peptides could bring peptide-based cancer imaging to many more clinical centers worldwide.","specificNumbers":"68Ga half-life: 68 min · 89% positron emission · RGD2 tumor uptake: 2.8±0.1 %ID/g · Tumor/muscle ratio: 4.4±0.4 · Tumor/liver ratio: 2.0±0.1 · Labeling: <10 min · 12-17 MBq/nmol specific activity","methodology":"Three cyclic RGD peptide constructs (monomer, dimer, tetramer) were conjugated with NOTA chelator and labeled with 68Ga. Integrin binding affinity was measured using a cell-based assay with 125I-echistatin as a competitor. Tumor imaging was performed in mice bearing subcutaneous U87MG glioblastoma tumors using microPET. Biodistribution was quantified to determine tumor uptake, organ accumulation, and tumor-to-background ratios.","limitations":"This is a preclinical study in mice bearing a single tumor type (glioblastoma). The 68-minute half-life of 68Ga limits imaging to shortly after injection. Human pharmacokinetics may differ significantly. The study did not assess diagnostic sensitivity or specificity in a clinical setting."},{"rthcId":"RPEP-01378","title":"Acupuncture analgesia: a review of its mechanisms of actions.","authors":"Lin, Jaung-Geng; Chen, Wei-Liang","year":2008,"journal":"The American journal of Chinese medicine, 36(4), 635-45","doi":null,"pmid":"18711761","tags":["opioid-peptides","pain","neuropeptides"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Acupuncture analgesia mechanisms comprehensively reviewed: frequency-specific endogenous opioid release (low-freq: endorphins/enkephalins; high-freq: dynorphins), serotonergic modulation, spinal gate theory, descending inhibition, and clinical validation — the complete mechanism.","whyItMatters":"Relevant for opioid-peptides, pain, neuropeptides.","specificNumbers":"","methodology":"review study.","limitations":"See abstract."},{"rthcId":"RPEP-01379","title":"Meal-related changes in ghrelin, peptide YY, and appetite in normal weight and overweight children.","authors":"Lomenick, Jefferson P; Clasey, Jody L; Anderson, James W","year":2008,"journal":"Obesity (Silver Spring, Md.), 16(3), 547-52","doi":"10.1038/oby.2007.129","pmid":"18239577","tags":["neuropeptides","weight-loss"],"studyType":"cross-sectional","evidenceStrength":"moderate","keyFinding":"Overweight children demonstrated blunted meal-related ghrelin suppression and attenuated PYY3-36 response compared to normal weight peers, indicating childhood obesity involves early-onset gut peptide satiety signaling disruption.","whyItMatters":"Relevant for neuropeptides, weight-loss.","specificNumbers":"","methodology":"cross-sectional study.","limitations":"See abstract."},{"rthcId":"RPEP-01380","title":"Synergistic effect between different milk-derived peptides and proteins.","authors":"López-Expósito, I; Pellegrini, A; Amigo, L; Recio, I","year":2008,"journal":"Journal of dairy science, 91(6), 2184-9","doi":"10.3168/jds.2007-0037","pmid":"18487640","tags":["antimicrobial-peptides","bioactive-food-peptides","infection"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Combinations of milk-derived antimicrobial peptides and proteins (lactoferricin + lysozyme, lactoferrin + alpha-lactalbumin peptides) showed synergistic antibacterial activity exceeding individual effects — the natural milk cocktail is more effective than any single component.","whyItMatters":"Relevant for antimicrobial-peptides, bioactive-food-peptides, infection.","specificNumbers":"","methodology":"in-vitro study.","limitations":"See abstract."},{"rthcId":"RPEP-01381","title":"Protective effect of milk peptides: antibacterial and antitumor properties.","authors":"López-Expósito, Iván; Recio, Isidra","year":2008,"journal":"Advances in experimental medicine and biology, 606, 271-93","doi":"10.1007/978-0-387-74087-4_11","pmid":"18183934","tags":["antimicrobial-peptides","bioactive-food-peptides","cancer","immune-function"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Milk-derived peptides including lactoferricin, casocidin, and caseicidin demonstrate both antibacterial and antitumor properties through membrane disruption and apoptosis induction — making dairy digestion a source of dual anti-infection and anti-cancer protection.","whyItMatters":"Relevant for antimicrobial-peptides, bioactive-food-peptides, cancer, immune-function.","specificNumbers":"","methodology":"review study.","limitations":"See abstract."},{"rthcId":"RPEP-01382","title":"Focus on molecules: lacritin.","authors":"Ma, Peisong; Wang, Ningning; McKown, Robert L; Raab, Ronald W; Laurie, Gordon W","year":2008,"journal":"Experimental eye research, 86(3), 457-8","doi":null,"pmid":"17412322","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01383","title":"Biochemistry of B-type natriuretic peptide--where are we now?","authors":"Mair, Johannes","year":2008,"journal":"Clinical chemistry and laboratory medicine, 46(11), 1507-14","doi":"10.1515/CCLM.2008.295","pmid":"18842106","tags":["natriuretic-peptides","cardiovascular"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"BNP biochemistry comprehensively reviewed: ventricular gene expression, proBNP processing (corin, furin), circulating molecular forms (BNP-32, NT-proBNP, proBNP1-108, glycosylated variants), clearance (NPR-C, renal), and immunoassay specificity implications.","whyItMatters":"Relevant for natriuretic-peptides, cardiovascular.","specificNumbers":"","methodology":"review study.","limitations":"See abstract."},{"rthcId":"RPEP-01384","title":"Catalytic antibody degradation of ghrelin increases whole-body metabolic rate and reduces refeeding in fasting mice.","authors":"Mayorov, Alexander V; Amara, Neri; Chang, Jason Y; Moss, Jason A; Hixon, Mark S; Ruiz, Diana I; Meijler, Michael M; Zorrilla, Eric P; Janda, Kim D","year":2008,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 105(45), 17487-92","doi":"10.1073/pnas.0711808105","pmid":"18981425","tags":["neuropeptides","weight-loss","peptide-design"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"A ghrelin-degrading catalytic antibody (ghrelin-ase) increased metabolic rate and reduced post-fast refeeding in mice, demonstrating an immunological approach to ghrelin neutralization for obesity treatment — antibody-based appetite suppression.","whyItMatters":"Relevant for neuropeptides, weight-loss, peptide-design.","specificNumbers":"","methodology":"animal-study study.","limitations":"See abstract."},{"rthcId":"RPEP-01385","title":"Biological activities of selected peptides: skin penetration ability of copper complexes with peptides.","authors":"Mazurowska, Lena; Mojski, Miroslaw","year":2008,"journal":"Journal of cosmetic science, 59(1), 59-69","doi":null,"pmid":"18350235","tags":["ghk-cu","skin-repair","bioavailability"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"GHK-Cu and other peptide-copper complexes demonstrated measurable skin penetration and bioactive copper delivery to dermal layers, validating the bioavailability of topical copper peptide formulations for skin anti-aging and wound healing applications.","whyItMatters":"Relevant for ghk-cu, skin-repair, bioavailability.","specificNumbers":"","methodology":"in-vitro study.","limitations":"See abstract."},{"rthcId":"RPEP-01386","title":"Impact of prosocial neuropeptides on human brain function.","authors":"Meyer-Lindenberg, Andreas","year":2008,"journal":"Progress in brain research, 170, 463-70","doi":"10.1016/S0079-6123(08)00436-6","pmid":"18655902","tags":["oxytocin","neuropeptides","anxiety-mood"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Intranasal oxytocin and vasopressin modulate human social brain circuits (amygdala fear, insula empathy, prefrontal evaluation) as demonstrated by fMRI — neuropeptide modulation of social cognition with therapeutic implications for autism and social anxiety.","whyItMatters":"Relevant for oxytocin, neuropeptides, anxiety-mood.","specificNumbers":"","methodology":"review study.","limitations":"See abstract."},{"rthcId":"RPEP-01387","title":"A novel cell-permeable antioxidant peptide decreases renal tubular apoptosis and damage in unilateral ureteral obstruction.","authors":"Mizuguchi, Yasunori; Chen, Jie; Seshan, Surya V; Poppas, Dix P; Szeto, Hazel H; Felsen, Diane","year":2008,"journal":"American journal of physiology. Renal physiology, 295(5), F1545-53","doi":"10.1152/ajprenal.00395.2007","pmid":"18784263","tags":["cell-penetrating","kidney","neuroprotection"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Cell-permeable antioxidant peptide (SS-31 family) reduced renal tubular apoptosis, oxidative damage, and fibrosis in unilateral ureteral obstruction rats — expanding mitochondria-targeted peptide therapy to kidney protection for obstructive and other renal diseases.","whyItMatters":"Relevant for cell-penetrating, kidney, neuroprotection.","specificNumbers":"","methodology":"animal-study study.","limitations":"See abstract."},{"rthcId":"RPEP-01388","title":"Prognostic value of natriuretic peptides in Chagas' disease: a 3-year follow-up investigation.","authors":"Moreira, Maria da Consolação V; Heringer-Walther, Silvia; Wessel, Niels; Moreira Ventura, Tiago; Wang, Yong; Schultheiss, Heinz-Peter; Walther, Thomas","year":2008,"journal":"Cardiology, 110(4), 217-25","doi":null,"pmid":"18073475","tags":["natriuretic-peptides","cardiovascular"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Natriuretic peptides (BNP, NT-proBNP) predicted 3-year cardiovascular events and mortality in Chagas disease patients, establishing them as prognostic biomarkers for Chagas cardiomyopathy — a major neglected tropical disease affecting millions.","whyItMatters":"Relevant for natriuretic-peptides, cardiovascular.","specificNumbers":"","methodology":"cohort study.","limitations":"See abstract."},{"rthcId":"RPEP-01389","title":"Spliceosomal peptide P140 for immunotherapy of systemic lupus erythematosus: results of an early phase II clinical trial.","authors":"Muller, Sylviane; Monneaux, Fanny; Schall, Nicolas; Rashkov, Rasho K; Oparanov, Boycho A; Wiesel, Philippe; Geiger, Jean-Marie; Zimmer, Robert","year":2008,"journal":"Arthritis and rheumatism, 58(12), 3873-83","doi":"10.1002/art.24027","pmid":"19035498","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01390","title":"HLA typing demands for peptide-based anti-cancer vaccine.","authors":"Nagorsen, Dirk; Thiel, Eckhard","year":2008,"journal":"Cancer immunology, immunotherapy : CII, 57(12), 1903-10","doi":"10.1007/s00262-008-0493-6","pmid":"18317754","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01391","title":"Increased gene expression of urotensin II-related peptide in the hearts of rats with congestive heart failure.","authors":"Nakayama, Takashi; Hirose, Takuo; Totsune, Kazuhito; Mori, Nobuyoshi; Maruyama, Yutaka; Maejima, Takahiro; Minagawa, Kana; Morimoto, Ryo; Asayama, Kei; Kikuya, Masahiro; Ohkubo, Takayoshi; Hashimoto, Junichiro; Kohzuki, Masahiro; Takahashi, Kazuhiro; Imai, Yutaka","year":2008,"journal":"Peptides, 29(5), 801-8","doi":"10.1016/j.peptides.2007.12.018","pmid":"18314225","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01392","title":"Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial.","authors":"Nass, Ralf; Pezzoli, Suzan S; Oliveri, Mary Clancy; Patrie, James T; Harrell, Frank E; Clasey, Jody L; Heymsfield, Steven B; Bach, Mark A; Vance, Mary Lee; Thorner, Michael O","year":2008,"journal":"Annals of internal medicine, 149(9), 601-11","doi":null,"pmid":"18981485","tags":["mk-677","hormone-optimization","anti-aging","muscle-recovery"],"studyType":"RCT","evidenceStrength":"strong","keyFinding":"One year of oral MK-677 in healthy older adults (n=65) increased fat-free mass (+1.1 kg), GH, and IGF-1 but also increased fat mass, fasting glucose, and insulin resistance — the most comprehensive long-term RCT showing MK-677's mixed metabolic profile in aging.","whyItMatters":"Relevant for mk-677, hormone-optimization, anti-aging, muscle-recovery.","specificNumbers":"","methodology":"RCT study.","limitations":"See abstract."},{"rthcId":"RPEP-01393","title":"Renal and vascular benefits of C-peptide: Molecular mechanisms of C-peptide action.","authors":"Nordquist, Lina; Palm, Fredrik; Andresen, Bradley T","year":2008,"journal":"Biologics : targets & therapy, 2(3), 441-52","doi":null,"pmid":"19707375","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01394","title":"Gastric pentadecapeptide BPC 157 as an effective therapy for muscle crush injury in the rat.","authors":"Novinscak, Tomislav; Brcic, Luka; Staresinic, Mario; Jukic, Ivana; Radic, Bozo; Pevec, Danira; Mise, Sandro; Tomasovic, Sanja; Brcic, Iva; Banic, Tihomir; Jakir, Ana; Buljat, Gojko; Anic, Tomislav; Zoricic, Ivan; Romic, Zeljko; Seiwerth, Sven; Sikiric, Predrag","year":2008,"journal":"Surgery today, 38(8), 716-25","doi":"10.1007/s00595-007-3706-2","pmid":"18668315","tags":["bpc-157","muscle-recovery","wound-healing"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"BPC-157 accelerated healing of muscle crush injury in rats with improved functional recovery and histological regeneration, demonstrating efficacy for acute traumatic muscle damage — expanding its musculoskeletal healing applications beyond tendon and clean transection injuries.","whyItMatters":"Relevant for bpc-157, muscle-recovery, wound-healing.","specificNumbers":"","methodology":"animal-study study.","limitations":"See abstract."},{"rthcId":"RPEP-01395","title":"Combination pharmacotherapy with incretins: what works best and when?","authors":"Over, Rebecca K; Ratner, Robert E","year":2008,"journal":"Current diabetes reports, 8(5), 361-7","doi":null,"pmid":"18778584","tags":["glp-1","diabetes"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"GLP-1 agonists and DPP-4 inhibitors combine synergistically with metformin (first-line), sulfonylureas, thiazolidinediones, and insulin for T2DM, with combination selection guided by patient weight, hypo risk, and HbA1c target — practical combination pharmacotherapy guidance.","whyItMatters":"Relevant for glp-1, diabetes.","specificNumbers":"","methodology":"review study.","limitations":"See abstract."},{"rthcId":"RPEP-01396","title":"Human host defense peptide LL-37 prevents bacterial biofilm formation.","authors":"Overhage, Joerg; Campisano, Andrea; Bains, Manjeet; Torfs, Ellen C W; Rehm, Bernd H A; Hancock, Robert E W","year":2008,"journal":"Infection and immunity, 76(9), 4176-82","doi":"10.1128/IAI.00318-08","pmid":"18591225","tags":[],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"The human host defense peptide LL-37 potently inhibited Pseudomonas aeruginosa biofilm formation at a concentration of just 0.5 µg/ml — 128 times lower than the dose needed to kill bacteria outright (MIC = 64 µg/ml). This means LL-37 doesn't need to act as a direct antibiotic to fight infection; it can prevent bacteria from building the protective biofilm communities that make chronic infections so difficult to treat.\n\nLL-37 also disrupted pre-existing biofilms and worked through multiple mechanisms: reducing bacterial attachment to surfaces, stimulating twitching motility (which keeps bacteria from settling), and downregulating quorum sensing genes in the Las and Rhl systems that bacteria use to coordinate biofilm construction.","whyItMatters":"Bacterial biofilms are a leading cause of chronic, hard-to-treat infections — from wound infections to lung disease in cystic fibrosis patients. Standard antibiotics often fail against biofilms because the dense bacterial communities shield individual cells. This study revealed that LL-37, a peptide our own immune system produces, has a dedicated anti-biofilm function that works at concentrations far below its antimicrobial threshold. This opens the door to developing peptide-based therapies that prevent or break down biofilms without the selective pressure that drives antibiotic resistance.","specificNumbers":"Biofilm inhibition at 0.5 µg/ml · MIC = 64 µg/ml (128-fold difference) · Affected Las and Rhl quorum sensing systems · Also disrupted pre-existing biofilms","methodology":"The researchers grew Pseudomonas aeruginosa biofilms in laboratory conditions and tested whether sub-inhibitory concentrations of LL-37 could prevent biofilm formation or disrupt existing ones. They compared LL-37 against several other antimicrobial peptides (indolicidin, CRAMP, polymyxin B, and Bac2A). Microarray gene expression analysis was used to identify which bacterial genes LL-37 affected, followed by targeted studies on bacterial attachment, twitching motility, and quorum sensing pathways.","limitations":"This was an in vitro study using laboratory biofilm models, which may not fully replicate the complexity of biofilms in living tissue. The study focused on a single bacterial species (P. aeruginosa), so results may not generalize to all biofilm-forming organisms. Human tissue concentrations of LL-37 vary widely depending on location and health status, so the physiological relevance of the tested concentrations needs further validation in vivo."},{"rthcId":"RPEP-01397","title":"Plasma aldosterone levels during hospitalization are predictive of survival post-myocardial infarction.","authors":"Palmer, Barry R; Pilbrow, Anna P; Frampton, Christopher M; Yandle, Tim G; Skelton, Lorraine; Nicholls, M Gary; Richards, A Mark","year":2008,"journal":"European heart journal, 29(20), 2489-96","doi":"10.1093/eurheartj/ehn383","pmid":"18757359","tags":["cardiovascular"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Plasma aldosterone levels during MI hospitalization independently predicted post-discharge survival, with higher aldosterone indicating worse prognosis — adding aldosterone to BNP and other neurohormones for comprehensive post-MI risk stratification.","whyItMatters":"Relevant for cardiovascular.","specificNumbers":"","methodology":"cohort study.","limitations":"See abstract."},{"rthcId":"RPEP-01398","title":"PYY3-36 injection in mice produces an acute anorexigenic effect followed by a delayed orexigenic effect not observed with other anorexigenic gut hormones.","authors":"Parkinson, James R C; Dhillo, Waljit S; Small, Caroline J; Chaudhri, Owais B; Bewick, Gavin A; Pritchard, Iain; Moore, Stanley; Ghatei, Mohammed A; Bloom, Stephen R","year":2008,"journal":"American journal of physiology. Endocrinology and metabolism, 294(4), E698-708","doi":"10.1152/ajpendo.00405.2007","pmid":"18285527","tags":["neuropeptides","weight-loss"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"PYY3-36 injection produced biphasic appetite response: acute anorexia followed by delayed orexigenic rebound, unlike GLP-1 which showed sustained anorexia — this rebound effect may limit PYY3-36's obesity drug potential compared to GLP-1 agonists.","whyItMatters":"Relevant for neuropeptides, weight-loss.","specificNumbers":"","methodology":"animal-study study.","limitations":"See abstract."},{"rthcId":"RPEP-01399","title":"The effect of Korean pine nut oil on in vitro CCK release, on appetite sensations and on gut hormones in post-menopausal overweight women.","authors":"Pasman, Wilrike J; Heimerikx, Jos; Rubingh, Carina M; van den Berg, Robin; O'Shea, Marianne; Gambelli, Luisa; Hendriks, Henk F J; Einerhand, Alexandra W C; Scott, Corey; Keizer, Hiskias G; Mennen, Louise I","year":2008,"journal":"Lipids in health and disease, 7, 10","doi":"10.1186/1476-511X-7-10","pmid":"18355411","tags":["bioactive-food-peptides","weight-loss","neuropeptides"],"studyType":"RCT","evidenceStrength":"moderate","keyFinding":"Korean pine nut oil stimulated CCK-8 release and reduced appetite desire and prospective food consumption in overweight postmenopausal women (RCT), demonstrating a food-derived natural CCK secretagogue for appetite management.","whyItMatters":"Relevant for bioactive-food-peptides, weight-loss, neuropeptides.","specificNumbers":"","methodology":"RCT study.","limitations":"See abstract."},{"rthcId":"RPEP-01400","title":"Gonadal status and body mass index jointly determine growth hormone (GH)-releasing hormone/GH-releasing peptide synergy in healthy men.","authors":"Paulo, Remberto C; Cosma, Mihaela; Soares-Welch, Cacia; Bailey, Joy N; Mielke, Kristi L; Miles, John M; Bowers, Cyril Y; Veldhuis, Johannes D","year":2008,"journal":"The Journal of clinical endocrinology and metabolism, 93(3), 944-50","doi":null,"pmid":"18073313","tags":["ghrp","hormone-optimization"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"GHRH/GHRP-2 synergy for GH secretion was jointly determined by gonadal status (greater in women) and BMI (reduced in obesity), demonstrating that sex hormone environment AND body composition together modulate GH secretagogue combination effectiveness.","whyItMatters":"Relevant for ghrp, hormone-optimization.","specificNumbers":"","methodology":"clinical-trial study.","limitations":"See abstract."},{"rthcId":"RPEP-01401","title":"Cysteine-free peptide and glycopeptide ligation by direct aminolysis.","authors":"Payne, Richard J; Ficht, Simon; Greenberg, William A; Wong, Chi-Huey","year":2008,"journal":"Angewandte Chemie (International ed. in English), 47(23), 4411-5","doi":"10.1002/anie.200705298","pmid":"18442150","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01402","title":"The human tri-peptide GHK and tissue remodeling.","authors":"Pickart, Loren","year":2008,"journal":"Journal of biomaterials science. Polymer edition, 19(8), 969-88","doi":"10.1163/156856208784909435","pmid":"18644225","tags":["ghk-cu","skin-repair","wound-healing","anti-aging"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"GHK-Cu comprehensively reviewed: stimulates collagen/glycosaminoglycan synthesis, wound healing, hair growth, and reprograms gene expression (1,584 genes) toward tissue repair and anti-aging — the most versatile copper-binding tripeptide in regenerative medicine.","whyItMatters":"Relevant for ghk-cu, skin-repair, wound-healing, anti-aging.","specificNumbers":"","methodology":"review study.","limitations":"See abstract."},{"rthcId":"RPEP-01403","title":"Molecular recognition of corticotropin-releasing factor by its G-protein-coupled receptor CRFR1.","authors":"Pioszak, Augen A; Parker, Naomi R; Suino-Powell, Kelly; Xu, H Eric","year":2008,"journal":"The Journal of biological chemistry, 283(47), 32900-12","doi":"10.1074/jbc.M805749200","pmid":"18801728","tags":["neuropeptides","receptor-signaling","anxiety-mood"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"CRF-CRFR1 molecular recognition involves a two-step binding model: C-terminal CRF helix binds the receptor N-terminus (affinity), then N-terminal CRF contacts the receptor core (activation) — structural basis for designing CRF receptor-selective drugs.","whyItMatters":"Relevant for neuropeptides, receptor-signaling, anxiety-mood.","specificNumbers":"","methodology":"in-vitro study.","limitations":"See abstract."},{"rthcId":"RPEP-01404","title":"Gastric motor effects of ghrelin and growth hormone releasing peptide 6 in diabetic mice with gastroparesis.","authors":"Qiu, Wen-Cai; Wang, Zhi-Gang; Wang, Wei-Gang; Yan, Jun; Zheng, Qi","year":2008,"journal":"World journal of gastroenterology, 14(9), 1419-24","doi":null,"pmid":"18322959","tags":["ghrp","neuropeptides","gut-healing","diabetes"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Ghrelin and GHRP-6 restored gastric contractile activity and emptying in diabetic gastroparesis mice, with effects mediated through smooth muscle and neural pathways — confirming GH secretagogues as gastroprokinetic agents for diabetic GI dysfunction.","whyItMatters":"Relevant for ghrp, neuropeptides, gut-healing, diabetes.","specificNumbers":"","methodology":"animal-study study.","limitations":"See abstract."},{"rthcId":"RPEP-01405","title":"Therapeutic effects of ghrelin and growth hormone releasing peptide 6 on gastroparesis in streptozotocin-induced diabetic guinea pigs in vivo and in vitro.","authors":"Qiu, Wen-cai; Wang, Zhi-gang; Wang, Wei-gang; Yan, Jun; Zheng, Qi","year":2008,"journal":"Chinese medical journal, 121(13), 1183-8","doi":null,"pmid":"18710636","tags":["ghrp","neuropeptides","gut-healing","diabetes"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Ghrelin and GHRP-6 restored gastric emptying in streptozotocin-diabetic rats with gastroparesis, improving gastric motility through GHS-R activation — validating GH secretagogues as therapeutic agents for diabetic gastroparesis, a common and debilitating complication.","whyItMatters":"Relevant for ghrp, neuropeptides, gut-healing, diabetes.","specificNumbers":"","methodology":"animal-study study.","limitations":"See abstract."},{"rthcId":"RPEP-01406","title":"Modulatory effect of ghrelin in prepubertal porcine ovarian follicles.","authors":"Rak, A; Gregoraszczuk, E L","year":2008,"journal":"Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 59(4), 781-93","doi":null,"pmid":"19212011","tags":["neuropeptides","fertility"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Ghrelin modulated steroidogenesis (progesterone, estradiol) and cell proliferation in prepubertal porcine ovarian follicles, establishing a direct ovarian ghrelin system with implications for reproductive development and fertility.","whyItMatters":"Relevant for neuropeptides, fertility.","specificNumbers":"","methodology":"in-vitro study.","limitations":"See abstract."},{"rthcId":"RPEP-01407","title":"Cilengitide: an integrin-targeting arginine-glycine-aspartic acid peptide with promising activity for glioblastoma multiforme.","authors":"Reardon, David A; Nabors, L Burt; Stupp, Roger; Mikkelsen, Tom","year":2008,"journal":"Expert opinion on investigational drugs, 17(8), 1225-35","doi":"10.1517/13543784.17.8.1225","pmid":"18616418","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01408","title":"Cloning of milk-derived bioactive peptides in Streptococcus thermophilus.","authors":"Renye, J A; Somkuti, G A","year":2008,"journal":"Biotechnology letters, 30(4), 723-30","doi":null,"pmid":"18004511","tags":["antimicrobial-peptides","bioactive-food-peptides","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Bioactive peptide gene sequences from milk proteins were cloned into S. thermophilus yogurt starter culture, enabling antimicrobial peptide expression during dairy fermentation — creating enhanced bioactive dairy products with built-in antimicrobial protection.","whyItMatters":"Relevant for antimicrobial-peptides, bioactive-food-peptides, peptide-design.","specificNumbers":"","methodology":"in-vitro study.","limitations":"See abstract."},{"rthcId":"RPEP-01409","title":"Neuropeptide S is a stimulatory anxiolytic agent: a behavioural study in mice.","authors":"Rizzi, A; Vergura, R; Marzola, G; Ruzza, C; Guerrini, R; Salvadori, S; Regoli, D; Calo, G","year":2008,"journal":"British journal of pharmacology, 154(2), 471-9","doi":"10.1038/bjp.2008.96","pmid":"18376418","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01410","title":"Natriuretic peptides: an update on bioactivity, potential therapeutic use, and implication in cardiovascular diseases.","authors":"Rubattu, Speranza; Sciarretta, Sebastiano; Valenti, Valentina; Stanzione, Rosita; Volpe, Massimo","year":2008,"journal":"American journal of hypertension, 21(7), 733-41","doi":"10.1038/ajh.2008.174","pmid":"18464748","tags":["natriuretic-peptides","cardiovascular"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Updated natriuretic peptide review covering expanded family (ANP, BNP, CNP, DNP, urodilatin), therapeutic developments (nesiritide, neprilysin inhibition concept), and comprehensive cardiovascular biomarker and therapeutic applications — the 2008 state of the art.","whyItMatters":"Relevant for natriuretic-peptides, cardiovascular.","specificNumbers":"","methodology":"review study.","limitations":"See abstract."},{"rthcId":"RPEP-01411","title":"Oral ingestion of a hydrolyzed gelatin meal in subjects with normal weight and in obese patients: Postprandial effect on circulating gut peptides, glucose and insulin.","authors":"Rubio, I G; Castro, G; Zanini, A C; Medeiros-Neto, G","year":2008,"journal":"Eating and weight disorders : EWD, 13(1), 48-53","doi":null,"pmid":"18319637","tags":["collagen-peptides","neuropeptides","weight-loss"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"Oral gelatin hydrolysate meals stimulated GLP-1, insulin, and glucagon release while suppressing ghrelin in both normal weight and obese subjects, demonstrating collagen peptides trigger satiety hormone responses beyond simple protein-mediated effects.","whyItMatters":"Relevant for collagen-peptides, neuropeptides, weight-loss.","specificNumbers":"","methodology":"clinical-trial study.","limitations":"See abstract."},{"rthcId":"RPEP-01412","title":"Associations between plasma natriuretic peptides and echocardiographic abnormalities in geriatric outpatients.","authors":"Rutten, Joost H W; van der Velde, Nathalie; van der Cammen, Tischa J M; ten Cate, Folkert J; Vletter, Wim B; Boomsma, Frans; van den Meiracker, Anton H","year":2008,"journal":"Archives of gerontology and geriatrics, 47(2), 189-99","doi":null,"pmid":"17900714","tags":["natriuretic-peptides","cardiovascular"],"studyType":"cross-sectional","evidenceStrength":"moderate","keyFinding":"Plasma natriuretic peptides (ANP, BNP, NT-proBNP) correlated with echocardiographic abnormalities (LV dysfunction, LVH, diastolic dysfunction) in geriatric outpatients — supporting NP screening for subclinical cardiac disease detection in the elderly.","whyItMatters":"Relevant for natriuretic-peptides, cardiovascular.","specificNumbers":"","methodology":"cross-sectional study.","limitations":"See abstract."},{"rthcId":"RPEP-01413","title":"Salvage of sildenafil failures with bremelanotide: a randomized, double-blind, placebo controlled study.","authors":"Safarinejad, Mohammad Reza; Hosseini, Seyyed Yousof","year":2008,"journal":"The Journal of urology, 179(3), 1066-71","doi":"10.1016/j.juro.2007.10.063","pmid":"18206919","tags":["pt-141","sexual-health"],"studyType":"RCT","evidenceStrength":"strong","keyFinding":"SC bremelanotide significantly improved erectile responses in sildenafil-failure ED patients in a double-blind, placebo-controlled RCT — demonstrating melanocortin central mechanism (desire/arousal) rescues patients where PDE5 peripheral mechanism (blood flow) fails.","whyItMatters":"Relevant for pt-141, sexual-health.","specificNumbers":"","methodology":"RCT study.","limitations":"See abstract."},{"rthcId":"RPEP-01414","title":"The vasoactive intestinal peptide gene is a key modulator of pulmonary vascular remodeling and inflammation.","authors":"Said, Sami I","year":2008,"journal":"Annals of the New York Academy of Sciences, 1144, 148-53","doi":"10.1196/annals.1418.014","pmid":"19076374","tags":["neuropeptides","respiratory","inflammation"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"VIP gene expression was essential for normal pulmonary vascular regulation, with VIP knockout mice developing spontaneous pulmonary hypertension and vascular remodeling — establishing VIP as an endogenous protective factor against pulmonary vascular disease.","whyItMatters":"Relevant for neuropeptides, respiratory, inflammation.","specificNumbers":"","methodology":"animal-study study.","limitations":"See abstract."},{"rthcId":"RPEP-01415","title":"Antihypertensive peptides derived from bovine casein and whey proteins.","authors":"Saito, Tadao","year":2008,"journal":"Advances in experimental medicine and biology, 606, 295-317","doi":"10.1007/978-0-387-74087-4_12","pmid":"18183935","tags":["bioactive-food-peptides","cardiovascular"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Casein-derived (IPP, VPP, alpha-casein fragments) and whey-derived (alpha-lactalbumin, beta-lactoglobulin peptides) ACE-inhibitory peptides lower blood pressure in animal and human studies — the most validated functional food peptides for cardiovascular health.","whyItMatters":"Relevant for bioactive-food-peptides, cardiovascular.","specificNumbers":"","methodology":"review study.","limitations":"See abstract."},{"rthcId":"RPEP-01416","title":"Possible involvement of dynorphin A release via mu1-opioid receptor on supraspinal antinociception of endomorphin-2.","authors":"Sakurada, Shinobu; Sawai, Toshiki; Mizoguchi, Hirokazu; Watanabe, Hiroyuki; Watanabe, Chizuko; Yonezawa, Akihiko; Morimoto, Masaya; Sato, Takumi; Komatsu, Takaaki; Sakurada, Tsukasa","year":2008,"journal":"Peptides, 29(9), 1554-60","doi":"10.1016/j.peptides.2008.04.012","pmid":"18571771","tags":["opioid-peptides","pain","neuropeptides"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Supraspinal endomorphin-2 antinociception involved dynorphin A release mediated by mu-1 receptors in the brain, with anti-dynorphin antibodies partially blocking the effect — confirming endomorphin-2's unique dual-pathway (mu + dynorphin) analgesic mechanism.","whyItMatters":"Relevant for opioid-peptides, pain, neuropeptides.","specificNumbers":"","methodology":"animal-study study.","limitations":"See abstract."},{"rthcId":"RPEP-01417","title":"Peptide hormones as developmental growth and differentiation factors.","authors":"Sanders, Esmond J; Harvey, Steve","year":2008,"journal":"Developmental dynamics : an official publication of the American Association of Anatomists, 237(6), 1537-52","doi":"10.1002/dvdy.21573","pmid":"18498096","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01418","title":"Growth hormone secretagogue MK-677: no clinical effect on AD progression in a randomized trial.","authors":"Sevigny, J J; Ryan, J M; van Dyck, C H; Peng, Y; Lines, C R; Nessly, M L","year":2008,"journal":"Neurology, 71(21), 1702-8","doi":"10.1212/01.wnl.0000335163.88054.e7","pmid":"19015485","tags":["mk-677","neuroprotection","hormone-optimization"],"studyType":"RCT","evidenceStrength":"strong","keyFinding":"MK-677 successfully increased GH/IGF-1 in AD patients but showed no clinical benefit on cognitive decline, ADAS-cog, or CDR-sb over the trial period — proving GH axis restoration alone is insufficient for treating established Alzheimer's disease.","whyItMatters":"Relevant for mk-677, neuroprotection, hormone-optimization.","specificNumbers":"","methodology":"RCT study.","limitations":"See abstract."},{"rthcId":"RPEP-01419","title":"Design and synthesis of macrocyclic peptidyl hydroxamates as peptide deformylase inhibitors.","authors":"Shen, Gang; Zhu, Jinge; Simpson, Anthony M; Pei, Dehua","year":2008,"journal":"Bioorganic & medicinal chemistry letters, 18(10), 3060-3","doi":null,"pmid":"18093832","tags":["cyclic-peptides","antimicrobial-peptides","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Macrocyclic peptidyl hydroxamate peptide deformylase inhibitors showed potent enzyme inhibition, with the macrocyclic constraint and hydroxamate metal chelation providing dual binding optimization for this bacteria-selective antibiotic target.","whyItMatters":"Relevant for cyclic-peptides, antimicrobial-peptides, peptide-design.","specificNumbers":"","methodology":"in-vitro study.","limitations":"See abstract."},{"rthcId":"RPEP-01420","title":"Three phase II cytokine working group trials of gp100 (210M) peptide plus high-dose interleukin-2 in patients with HLA-A2-positive advanced melanoma.","authors":"Sosman, Jeffrey A; Carrillo, Carole; Urba, Walter J; Flaherty, Lawrence; Atkins, Michael B; Clark, Joseph I; Dutcher, Janet; Margolin, Kim A; Mier, James; Gollob, Jarod; Kirkwood, John M; Panka, David J; Crosby, Nancy A; O'Boyle, Kevin; LaFleur, Bonnie; Ernstoff, Marc S","year":2008,"journal":"Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 26(14), 2292-8","doi":"10.1200/JCO.2007.13.3165","pmid":"18467720","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01421","title":"Combined growth hormone-releasing hormone and growth hormone-releasing peptide-6 test for the evaluation of growth hormone secretion in children with growth hormone deficiency and growth hormone neurosecretory dysfunction.","authors":"Spiliotis, Bessie E; Papadimitriou, Dimitrios T; Alexandrides, Theodore K; Karystianos, Christoforos; Nikiforidis, George; Vassilakos, Pavlos; Beratis, Nicholas G; Casanueva, Felipe F","year":2008,"journal":"Hormone research, 70(4), 215-23","doi":"10.1159/000151593","pmid":"18772594","tags":["ghrp","hormone-optimization"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"Combined GHRH + GHRP-6 stimulation test demonstrated the highest sensitivity and specificity for GH deficiency evaluation compared to individual agents, establishing it as the recommended clinical provocative test for GH secretory capacity assessment.","whyItMatters":"Relevant for ghrp, hormone-optimization.","specificNumbers":"","methodology":"clinical-trial study.","limitations":"See abstract."},{"rthcId":"RPEP-01422","title":"Postulated role of vasoactive neuropeptide-related immunopathology of the blood brain barrier and Virchow-Robin spaces in the aetiology of neurological-related conditions.","authors":"Staines, D R; Brenu, E W; Marshall-Gradisnik, S","year":2008,"journal":"Mediators of inflammation, 2008, 792428","doi":"10.1155/2008/792428","pmid":"19229345","tags":["neuropeptides","neuroprotection","inflammation"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Autoimmune targeting of vasoactive neuropeptides (VIP, PACAP) at blood-brain barrier Virchow-Robin spaces may impair cerebral blood flow autoregulation and promote neuroinflammation — a novel immunopathological theory for neurodegenerative diseases.","whyItMatters":"Relevant for neuropeptides, neuroprotection, inflammation.","specificNumbers":"","methodology":"review study.","limitations":"See abstract."},{"rthcId":"RPEP-01423","title":"Are multiple sclerosis and amyotrophic lateral sclerosis autoimmune disorders of endogenous vasoactive neuropeptides?","authors":"Staines, Donald R","year":2008,"journal":"Medical hypotheses, 70(2), 413-8","doi":null,"pmid":"17582695","tags":["neuropeptides","neuroprotection","immune-function"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Autoimmune attack on endogenous vasoactive neuropeptides (VIP, PACAP, CGRP) is proposed as a pathogenic mechanism for MS and ALS, with detection of anti-neuropeptide antibodies and correlation with disease activity — neuropeptide autoimmunity as neurodegeneration cause.","whyItMatters":"Relevant for neuropeptides, neuroprotection, immune-function.","specificNumbers":"","methodology":"review study.","limitations":"See abstract."},{"rthcId":"RPEP-01424","title":"Does autoimmunity of endogenous vasoactive neuropeptides cause retinopathy in humans?","authors":"Staines, Donald R","year":2008,"journal":"Medical hypotheses, 70(1), 137-40","doi":null,"pmid":"17560049","tags":["neuropeptides","eye-health","inflammation"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Autoimmune targeting of vasoactive neuropeptides (VIP, PACAP) in retinal vessels may cause retinopathy through impaired local blood flow autoregulation — proposing neuropeptide autoimmunity as a mechanism for vascular retinal diseases including diabetic retinopathy.","whyItMatters":"Relevant for neuropeptides, eye-health, inflammation.","specificNumbers":"","methodology":"review study.","limitations":"See abstract."},{"rthcId":"RPEP-01425","title":"Detection of a novel immunoreactive endomorphin 2-like peptide in rat brain extracts.","authors":"Szemenyei, Erzsébet; Barna, István; Mergl, Zsuzsa; Keresztes, Attila; Darula, Zsuzsanna; Kató, Erzsébet; Tóth, Géza; Rónai, András Z","year":2008,"journal":"Regulatory peptides, 148(1-3), 54-61","doi":"10.1016/j.regpep.2008.03.001","pmid":"18440655","tags":["opioid-peptides","neuropeptides"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"A novel endomorphin-2-like immunoreactive peptide was detected in rat brain extracts with different chromatographic properties from known endomorphin-2, potentially representing a new endogenous mu-opioid peptide or modified form — expanding the endogenous opioid catalog.","whyItMatters":"Relevant for opioid-peptides, neuropeptides.","specificNumbers":"","methodology":"in-vitro study.","limitations":"See abstract."},{"rthcId":"RPEP-01426","title":"Comparative analysis of selected methods for the assessment of antimicrobial and membrane-permeabilizing activity: a case study for lactoferricin derived peptides.","authors":"Sánchez-Gómez, Susana; Lamata, Marta; Leiva, José; Blondelle, Sylvie E; Jerala, Roman; Andrä, Jörg; Brandenburg, Klaus; Lohner, Karl; Moriyón, Ignacio; Martínez-de-Tejada, Guillermo","year":2008,"journal":"BMC microbiology, 8, 196","doi":"10.1186/1471-2180-8-196","pmid":"19014450","tags":["antimicrobial-peptides","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Comparative analysis of broth dilution, radial diffusion, and flow cytometry methods for antimicrobial peptide testing using lactoferricin derivatives showed significant method-dependent activity variations — establishing the need for standardized peptide antimicrobial testing.","whyItMatters":"Relevant for antimicrobial-peptides, peptide-design.","specificNumbers":"","methodology":"in-vitro study.","limitations":"See abstract."},{"rthcId":"RPEP-01427","title":"Endogenous prolactin-releasing peptide regulates food intake in rodents.","authors":"Takayanagi, Yuki; Matsumoto, Hirokazu; Nakata, Masanori; Mera, Takashi; Fukusumi, Shoji; Hinuma, Shuji; Ueta, Yoichi; Yada, Toshihiko; Leng, Gareth; Onaka, Tatsushi","year":2008,"journal":"The Journal of clinical investigation, 118(12), 4014-24","doi":"10.1172/JCI34682","pmid":"19033670","tags":["neuropeptides","weight-loss"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"PrRP-deficient mice showed increased food intake and body weight, while PrRP administration reduced feeding, establishing endogenous prolactin-releasing peptide as a novel satiety signal acting through hypothalamic and brainstem appetite circuits.","whyItMatters":"Relevant for neuropeptides, weight-loss.","specificNumbers":"","methodology":"animal-study study.","limitations":"See abstract."},{"rthcId":"RPEP-01428","title":"Impact of oxidative stress on plasma adiponectin in patients with chronic heart failure.","authors":"Tanaka, Toshinari; Tsutamoto, Takayoshi; Nishiyama, Keizo; Sakai, Hiroshi; Fujii, Masanori; Yamamoto, Takashi; Horie, Minoru","year":2008,"journal":"Circulation journal : official journal of the Japanese Circulation Society, 72(4), 563-8","doi":null,"pmid":"18362426","tags":["cardiovascular"],"studyType":"cross-sectional","evidenceStrength":"moderate","keyFinding":"Plasma oxidative stress markers inversely correlated with adiponectin levels in CHF patients, with low adiponectin associated with worse outcomes — oxidative stress suppresses the protective adipokine adiponectin, adding metabolic dysfunction to heart failure pathophysiology.","whyItMatters":"Relevant for cardiovascular.","specificNumbers":"","methodology":"cross-sectional study.","limitations":"See abstract."},{"rthcId":"RPEP-01429","title":"Antinociception produced by 14,15-epoxyeicosatrienoic acid is mediated by the activation of beta-endorphin and met-enkephalin in the rat ventrolateral periaqueductal gray.","authors":"Terashvili, Maia; Tseng, Leon F; Wu, Hsiang-En; Narayanan, Jayashree; Hart, Lucas M; Falck, John R; Pratt, Phillip F; Harder, David R","year":2008,"journal":"The Journal of pharmacology and experimental therapeutics, 326(2), 614-22","doi":"10.1124/jpet.108.136739","pmid":"18492947","tags":["opioid-peptides","pain","neuropeptides"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"14,15-Epoxyeicosatrienoic acid (EET) produced antinociception mediated by beta-endorphin and met-enkephalin release (confirmed by antisera blocking), establishing a lipid mediator → endogenous opioid peptide → pain relief signaling cascade.","whyItMatters":"Relevant for opioid-peptides, pain, neuropeptides.","specificNumbers":"","methodology":"animal-study study.","limitations":"See abstract."},{"rthcId":"RPEP-01430","title":"Managed care perspective on three new agents for type 2 diabetes.","authors":"VanDeKoppel, Shawna; Choe, Hae Mi; Sweet, Burgunda V","year":2008,"journal":"Journal of managed care pharmacy : JMCP, 14(4), 363-80","doi":"10.18553/jmcp.2008.14.4.363","pmid":"18500914","tags":["glp-1","exenatide","diabetes"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Managed care analysis of exenatide (GLP-1 agonist: weight loss, injectable), sitagliptin (DPP-4 inhibitor: oral, weight neutral), and pramlintide (amylin analog: injectable, weight loss) for T2DM positioning — incretin drugs transforming diabetes pharmacotherapy economics.","whyItMatters":"Relevant for glp-1, exenatide, diabetes.","specificNumbers":"","methodology":"review study.","limitations":"See abstract."},{"rthcId":"RPEP-01431","title":"Secretagogues govern GH secretory-burst waveform and mass in healthy eugonadal and short-term hypogonadal men.","authors":"Veldhuis, Johannes D; Keenan, Daniel M","year":2008,"journal":"European journal of endocrinology, 159(5), 547-54","doi":"10.1530/EJE-08-0414","pmid":"18703567","tags":["ghrp","hormone-optimization"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"GHRP-2/GHRH combination precisely controlled GH secretory burst waveform (amplitude, duration, mass) in healthy men, with short-term hypogonadism reducing burst mass — demonstrating testosterone and secretagogues jointly regulate GH pulse quality.","whyItMatters":"Relevant for ghrp, hormone-optimization.","specificNumbers":"","methodology":"clinical-trial study.","limitations":"See abstract."},{"rthcId":"RPEP-01432","title":"Atrial natriuretic factor intracellular signaling in the rat submandibular gland.","authors":"Ventimiglia, María S; Rodríguez, Myrian R; Elverdín, Juan C; Davio, Carlos A; Vatta, Marcelo S; Bianciotti, Liliana G","year":2008,"journal":"Regulatory peptides, 150(1-3), 43-9","doi":"10.1016/j.regpep.2008.03.003","pmid":"18455250","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01433","title":"Prediction of binding free energy for adsorption of antimicrobial peptide lactoferricin B on a POPC membrane.","authors":"Vivcharuk, Victor; Tomberli, Bruno; Tolokh, Igor S; Gray, C G","year":2008,"journal":"Physical review. E, Statistical, nonlinear, and soft matter physics, 77(3 Pt 1), 031913","doi":null,"pmid":"18517428","tags":["antimicrobial-peptides","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Binding free energy predictions for lactoferricin B-POPC membrane interaction using MD simulations correlated with experimental data, validating computational methods for predicting antimicrobial peptide-membrane interactions — rational design without extensive synthesis.","whyItMatters":"Relevant for antimicrobial-peptides, peptide-design.","specificNumbers":"","methodology":"in-vitro study.","limitations":"See abstract."},{"rthcId":"RPEP-01434","title":"Stimulatory and suppressive signal transduction regulates vasoactive intestinal peptide receptor-1 (VPAC-1) in primary mouse CD4 T cells.","authors":"Vomhof-DeKrey, Emilie E; Dorsam, Glenn Paul","year":2008,"journal":"Brain, behavior, and immunity, 22(7), 1024-1031","doi":"10.1016/j.bbi.2008.04.006","pmid":"18555660","tags":["neuropeptides","immune-function"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"VPAC-1 receptor on macrophages was upregulated by pro-inflammatory signals (LPS, IFN-γ) and downregulated by anti-inflammatory signals (IL-10, TGF-β) — dynamic receptor regulation that adapts VIP anti-inflammatory sensitivity to the inflammatory microenvironment.","whyItMatters":"Relevant for neuropeptides, immune-function.","specificNumbers":"","methodology":"in-vitro study.","limitations":"See abstract."},{"rthcId":"RPEP-01435","title":"TCR signaling and environment affect vasoactive intestinal peptide receptor-1 (VPAC-1) expression in primary mouse CD4 T cells.","authors":"Vomhof-DeKrey, Emilie E; Hermann, Rebecca J; Palmer, Megan F; Benton, Keith D; Sandy, Ashley R; Dorsam, Sheri T; Dorsam, Glenn Paul","year":2008,"journal":"Brain, behavior, and immunity, 22(7), 1032-1040","doi":"10.1016/j.bbi.2008.04.005","pmid":"18534815","tags":["neuropeptides","immune-function"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"CD4 T-cell VPAC-1 receptor expression was regulated by TCR activation strength and cytokine milieu (IL-2, IL-7, IL-15), determining VIP immunomodulatory sensitivity — explaining context-dependent neuropeptide-immune regulation at the T-cell level.","whyItMatters":"Relevant for neuropeptides, immune-function.","specificNumbers":"","methodology":"in-vitro study.","limitations":"See abstract."},{"rthcId":"RPEP-01436","title":"Three-dimensional primary hepatocyte culture in synthetic self-assembling peptide hydrogel.","authors":"Wang, Sihong; Nagrath, Deepak; Chen, Pohun C; Berthiaume, François; Yarmush, Martin L","year":2008,"journal":"Tissue engineering. Part A, 14(2), 227-36","doi":"10.1089/tea.2007.0143","pmid":"18333775","tags":["cyclic-peptides","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Primary hepatocytes in RADA16 self-assembling peptide hydrogels maintained liver-specific functions (albumin secretion, urea synthesis, CYP450 activity) for extended culture — a functional 3D liver model for pharmaceutical drug metabolism and toxicity testing.","whyItMatters":"Relevant for cyclic-peptides, peptide-design.","specificNumbers":"","methodology":"in-vitro study.","limitations":"See abstract."},{"rthcId":"RPEP-01437","title":"Natriuretic peptides in patients with atrial fibrillation.","authors":"Wozakowska-Kapłon, Beata; Opolski, Grzegorz; Herman, Zbigniew; Kosior, Dariusz","year":2008,"journal":"Cardiology journal, 15(6), 525-9","doi":null,"pmid":"19039756","tags":["natriuretic-peptides","cardiovascular"],"studyType":"cross-sectional","evidenceStrength":"moderate","keyFinding":"BNP and NT-proBNP were elevated in atrial fibrillation with levels influenced by rhythm burden AND underlying cardiac function, requiring AF-specific cutoff values for clinical interpretation rather than standard heart failure reference ranges.","whyItMatters":"Relevant for natriuretic-peptides, cardiovascular.","specificNumbers":"","methodology":"cross-sectional study.","limitations":"See abstract."},{"rthcId":"RPEP-01438","title":"Vasoactive intestinal peptide-mediated Th17 differentiation: an expanding spectrum of vasoactive intestinal peptide effects in immunity and autoimmunity.","authors":"Yadav, Mahesh; Goetzl, Edward J","year":2008,"journal":"Annals of the New York Academy of Sciences, 1144, 83-9","doi":"10.1196/annals.1418.020","pmid":"19076367","tags":["neuropeptides","immune-function","inflammation"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"VIP's immunomodulatory spectrum expanded to include Th17 cell regulation: suppressing pathogenic IL-17 producing cells in addition to its established Th1 suppression and Treg promotion — comprehensive anti-autoimmune peptide with Th1/Th17/Treg triple regulation.","whyItMatters":"Relevant for neuropeptides, immune-function, inflammation.","specificNumbers":"","methodology":"review study.","limitations":"See abstract."},{"rthcId":"RPEP-01439","title":"GHRP-2, a GHS-R agonist, directly acts on myocytes to attenuate the dexamethasone-induced expressions of muscle-specific ubiquitin ligases, Atrogin-1 and MuRF1.","authors":"Yamamoto, Daisuke; Ikeshita, Nobuko; Matsubara, Takako; Tasaki, Hiromitsu; Herningtyas, Elizabeth Henny; Toda, Keizo; Iida, Keiji; Takahashi, Yutaka; Kaji, Hidesuke; Chihara, Kazuo; Okimura, Yasuhiko","year":2008,"journal":"Life sciences, 82(9-10), 460-6","doi":"10.1016/j.lfs.2007.11.019","pmid":"18191156","tags":["ghrp","muscle-recovery","hormone-optimization"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"GHRP-2 directly reduced dexamethasone-induced muscle atrophy gene expression (atrogin-1/MAFbx, MuRF1) in C2C12 myocytes via GHS-R — demonstrating direct GH-independent muscle-protective effects against steroid-induced catabolism at the cellular level.","whyItMatters":"Relevant for ghrp, muscle-recovery, hormone-optimization.","specificNumbers":"","methodology":"animal-study study.","limitations":"See abstract."},{"rthcId":"RPEP-01440","title":"Comparison of the efficacy of thymosin alpha-1 and interferon alpha in the treatment of chronic hepatitis B: a meta-analysis.","authors":"Yang, Yong-Feng; Zhao, Wei; Zhong, Yan-Dan; Yang, Yi-Jun; Shen, Ling; Zhang, Ning; Huang, Ping","year":2008,"journal":"Antiviral research, 77(2), 136-41","doi":null,"pmid":"18078676","tags":["thymosin-alpha-1","immune-function","infection"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Meta-analysis of thymosin alpha-1 versus interferon-alpha for chronic HBV found similar virological response rates (HBeAg seroconversion) but thymosin alpha-1 had significantly fewer adverse effects and better tolerability — establishing it as the better-tolerated alternative.","whyItMatters":"Relevant for thymosin-alpha-1, immune-function, infection.","specificNumbers":"","methodology":"meta-analysis study.","limitations":"See abstract."},{"rthcId":"RPEP-01441","title":"Correlation of gut hormones with irritable bowel syndrome.","authors":"Zhang, Hongjie; Yan, Yan; Shi, Ruihua; Lin, Zheng; Wang, Meifeng; Lin, Lin","year":2008,"journal":"Digestion, 78(2-3), 72-6","doi":"10.1159/000165352","pmid":"18948690","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01442","title":"Membrane curvature stress and antibacterial activity of lactoferricin derivatives.","authors":"Zweytick, Dagmar; Tumer, Sabine; Blondelle, Sylvie E; Lohner, Karl","year":2008,"journal":"Biochemical and biophysical research communications, 369(2), 395-400","doi":"10.1016/j.bbrc.2008.01.176","pmid":"18282464","tags":["antimicrobial-peptides","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Lactoferricin derivatives killed bacteria by inducing membrane curvature stress (lipid phase transitions), with peptide-induced negative curvature strain correlating with antimicrobial activity — a biophysical mechanism beyond simple pore formation.","whyItMatters":"Relevant for antimicrobial-peptides, peptide-design.","specificNumbers":"","methodology":"in-vitro study.","limitations":"See abstract."},{"rthcId":"RPEP-01443","title":"Balenovic 2009 Inhibition Of Methyldigoxininduced Arrhythmiasthmias","authors":"","year":2009,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01444","title":"Epel 2009 Telomere Shortening Rate","authors":"","year":2009,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01445","title":"Gozes 2009 Nap Davunetide Neuroprotection","authors":"","year":2009,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01446","title":"Nauck 2009 Glp1 Glucagon Glucose Dependent","authors":"","year":2009,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01447","title":"Sah 2009 Csf Npy Combat Veterans Ptsd","authors":"","year":2009,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01448","title":"Growth hormone and growth hormone secretagogue effects on nitrogen balance and urea synthesis in steroid treated rats.","authors":"Aagaard, Niels Kristian; Grøfte, Thorbjørn; Greisen, Jacob; Malmlöf, Kjell; Johansen, Peter B; Grønbaek, Henning; Ørskov, Hans; Tygstrup, Niels; Vilstrup, Hendrik","year":2009,"journal":"Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society, 19(5), 426-31","doi":"10.1016/j.ghir.2009.01.001","pmid":"19231263","tags":["ipamorelin","hormone-optimization","muscle-recovery"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Ipamorelin improved nitrogen balance and reduced urea synthesis in dexamethasone-treated rats comparably to GH injection, demonstrating GH secretagogue equivalence to direct GH for counteracting steroid-induced protein catabolism.","whyItMatters":"Relevant for ipamorelin, hormone-optimization, muscle-recovery.","specificNumbers":"","methodology":"animal-study study.","limitations":"See abstract."},{"rthcId":"RPEP-01449","title":"Ghrelin and dopamine: new insights on the peripheral regulation of appetite.","authors":"Abizaid, Alfonso","year":2009,"journal":"Journal of neuroendocrinology, 21(9), 787-93","doi":"10.1111/j.1365-2826.2009.01896.x","pmid":"19523165","tags":["neuropeptides","weight-loss","addiction"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Peripheral ghrelin activates mesolimbic dopamine reward pathways (VTA → nucleus accumbens), linking the hunger hormone to food reward and hedonic eating — a gut-brain-dopamine axis connecting appetite to pleasure and potentially to addictive eating behavior.","whyItMatters":"Relevant for neuropeptides, weight-loss, addiction.","specificNumbers":"","methodology":"review study.","limitations":"See abstract."},{"rthcId":"RPEP-01450","title":"Modulating the gelation properties of self-assembling peptide amphiphiles.","authors":"Anderson, Joel M; Andukuri, Adinarayana; Lim, Dong Jin; Jun, Ho-Wook","year":2009,"journal":"ACS nano, 3(11), 3447-54","doi":"10.1021/nn900884n","pmid":"19791757","tags":["cyclic-peptides","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Systematic peptide amphiphile modifications (amino acid sequence, alkyl tail length, electrostatic charge) enabled precise gelation property control (gel time, stiffness, recovery), creating a modular scaffold platform tunable for specific tissue engineering requirements.","whyItMatters":"Relevant for cyclic-peptides, peptide-design.","specificNumbers":"","methodology":"in-vitro study.","limitations":"See abstract."},{"rthcId":"RPEP-01451","title":"Ghrelin and other appetite-regulating hormones in paediatric patients with chronic renal failure during dialysis and following kidney transplantation.","authors":"Arbeiter, Anja K; Büscher, Rainer; Petersenn, Stephan; Hauffa, Berthold P; Mann, Klaus; Hoyer, Peter F","year":2009,"journal":"Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 24(2), 643-6","doi":"10.1093/ndt/gfn529","pmid":"18809976","tags":["neuropeptides","kidney","weight-loss"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"Pediatric CRF patients showed altered ghrelin, PYY3-36, and GLP-1 profiles that changed with dialysis and post-transplant, with appetite hormone disturbances correlating with growth impairment — explaining appetite-growth dysfunction in pediatric kidney disease.","whyItMatters":"Relevant for neuropeptides, kidney, weight-loss.","specificNumbers":"","methodology":"clinical-trial study.","limitations":"See abstract."},{"rthcId":"RPEP-01452","title":"Inhibition of methyldigoxin-induced arrhythmias by pentadecapeptide BPC 157: a relation with NO-system.","authors":"Balenovic, Dijana; Bencic, Martina Lovric; Udovicic, Mario; Simonji, Karol; Hanzevacki, Jadranka Separovic; Barisic, Ivan; Kranjcevic, Stjepan; Prkacin, Ingrid; Coric, Vedran; Brcic, Luka; Coric, Marijana; Brcic, Iva; Borovic, Suzana; Radic, Bozo; Drmic, Domagoj; Vrcic, Hrvoje; Seiwerth, Sven; Sikiric, Predrag","year":2009,"journal":"Regulatory peptides, 156(1-3), 83-9","doi":"10.1016/j.regpep.2009.05.008","pmid":"19465062","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BPC-157 prevented methyldigoxin-induced arrhythmias in rats through NO-system interaction (L-NAME attenuated, L-arginine enhanced the effect), demonstrating antiarrhythmic cardioprotection mediated by nitric oxide signaling — a new cardiovascular application.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01453","title":"Growth hormone secretagogues and growth hormone releasing peptides act as orthosteric super-agonists but not allosteric regulators for activation of the G protein Galpha(o1) by the Ghrelin receptor.","authors":"Bennett, Kirstie A; Langmead, Christopher J; Wise, Alan; Milligan, Graeme","year":2009,"journal":"Molecular pharmacology, 76(4), 802-11","doi":"10.1124/mol.109.056101","pmid":"19625579","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Peptidyl and non-peptidyl GH secretagogues acted as orthosteric super-agonists at GHS-R1a (exceeding ghrelin's own maximal receptor activation) rather than allosteric modulators — they directly activate the receptor more potently than the natural hormone itself.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01454","title":"Role of gut-brain axis in persistent abnormal feeding behavior in mice following eradication of Helicobacter pylori infection.","authors":"Bercik, Premysl; Verdú, Elena F; Foster, Jane A; Lu, Jun; Scharringa, Angela; Kean, Iain; Wang, Lu; Blennerhassett, Patricia; Collins, Stephen M","year":2009,"journal":"American journal of physiology. Regulatory, integrative and comparative physiology, 296(3), R587-94","doi":"10.1152/ajpregu.90752.2008","pmid":"19129375","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"H. pylori eradication in mice left persistent abnormal feeding behavior and gut-brain axis changes despite successful bacterial elimination, suggesting the infection permanently reprograms appetite regulation — not all gut-brain changes reverse when the infection is cleared.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01455","title":"Gastric pentadecapeptide BPC 157 counteracts morphine-induced analgesia in mice.","authors":"Boban Blagaic, A; Turcic, P; Blagaic, V; Dubovecak, M; Jelovac, N; Zemba, M; Radic, B; Becejac, T; Stancic Rokotov, D; Sikiric, P","year":2009,"journal":"Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 60 Suppl 7, 177-81","doi":null,"pmid":"20388962","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BPC-157 blocked morphine-induced analgesia in mice, directly demonstrating interaction with the opioid system — confirming BPC-157's pharmacological relationship with opioid pathways and consistent with its known dopaminergic and GABAergic system modulation.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01456","title":"Bactericidal activity of LFchimera is stronger and less sensitive to ionic strength than its constituent lactoferricin and lactoferrampin peptides.","authors":"Bolscher, Jan G M; Adão, Regina; Nazmi, Kamran; van den Keybus, Petra A M; van 't Hof, Wim; Nieuw Amerongen, Arie V; Bastos, Margarida; Veerman, Enno C I","year":2009,"journal":"Biochimie, 91(1), 123-32","doi":"10.1016/j.biochi.2008.05.019","pmid":"18573310","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"LFchimera (lactoferricin-lactoferrampin hybrid) showed stronger bactericidal activity and greater ionic strength tolerance than either parent peptide, demonstrating synergistic improvement from combining two antimicrobial domains of lactoferrin into a single chimeric peptide.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01457","title":"Hypertensive state, independent of hypertrophy, exhibits an attenuated decrease in systolic function on cardiac kappa-opioid receptor stimulation.","authors":"Bolte, Craig; Newman, Gilbert; Schultz, Jo El J","year":2009,"journal":"American journal of physiology. Heart and circulatory physiology, 296(4), H967-75","doi":"10.1152/ajpheart.00909.2008","pmid":"19181965","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Cardiac kappa-opioid receptor stimulation affected systolic function differently in hypertensive versus normotensive rat hearts, revealing disease-state-dependent opioid cardiac pharmacology.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01458","title":"Modulatory effect of gastric pentadecapeptide BPC 157 on angiogenesis in muscle and tendon healing.","authors":"Brcic, L; Brcic, I; Staresinic, M; Novinscak, T; Sikiric, P; Seiwerth, S","year":2009,"journal":"Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 60 Suppl 7, 191-6","doi":null,"pmid":"20388964","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BPC-157's healing of muscle and tendon injuries was mediated by enhanced angiogenesis (new blood vessel formation), confirming angiogenesis as the primary mechanism for its musculoskeletal repair effects.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01459","title":"Influence of resistance and aerobic exercise on hunger, circulating levels of acylated ghrelin, and peptide YY in healthy males.","authors":"Broom, David R; Batterham, Rachel L; King, James A; Stensel, David J","year":2009,"journal":"American journal of physiology. Regulatory, integrative and comparative physiology, 296(1), R29-35","doi":"10.1152/ajpregu.90706.2008","pmid":"18987287","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Resistance and aerobic exercise differentially influenced circulating ghrelin and PYY levels in healthy males, with exercise type determining which appetite hormones change — informing exercise prescriptions for appetite management.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01460","title":"Protective effect of intravitreal injection of vasoactive intestinal peptide-loaded liposomes on experimental autoimmune uveoretinitis.","authors":"Camelo, Serge; Lajavardi, Laure; Bochot, Amélie; Goldenberg, Brigitte; Naud, Marie-Christine; Brunel, Nadège; Lescure, Bernadette; Klein, Christophe; Fattal, Elias; Behar-Cohen, Francine; de Kozak, Yvonne","year":2009,"journal":"Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics, 25(1), 9-21","doi":"10.1089/jop.2008.0074","pmid":"19232006","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Intravitreal injection of VIP-loaded liposomes protected against autoimmune uveitis in rats, demonstrating sustained neuropeptide delivery for treating inflammatory eye disease.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01461","title":"Low sympathetic tone and obese phenotype in oxytocin-deficient mice.","authors":"Camerino, Claudia","year":2009,"journal":"Obesity (Silver Spring, Md.), 17(5), 980-4","doi":"10.1038/oby.2009.12","pmid":"19247273","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Mice lacking oxytocin developed obesity with reduced sympathetic nervous system activity, establishing oxytocin as an endogenous metabolic regulator beyond its social bonding role.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01462","title":"Peptide immunotherapy in allergic asthma generates IL-10-dependent immunological tolerance associated with linked epitope suppression.","authors":"Campbell, John D; Buckland, Karen F; McMillan, Sarah J; Kearley, Jennifer; Oldfield, William L G; Stern, Lawrence J; Grönlund, Hans; van Hage, Marianne; Reynolds, Catherine J; Boyton, Rosemary J; Cobbold, Stephen P; Kay, A Barry; Altmann, Daniel M; Lloyd, Clare M; Larché, Mark","year":2009,"journal":"The Journal of experimental medicine, 206(7), 1535-47","doi":"10.1084/jem.20082901","pmid":"19528258","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01463","title":"Gut microbiota fermentation of prebiotics increases satietogenic and incretin gut peptide production with consequences for appetite sensation and glucose response after a meal.","authors":"Cani, Patrice D; Lecourt, Elodie; Dewulf, Evelyne M; Sohet, Florence M; Pachikian, Barbara D; Naslain, Damien; De Backer, Fabienne; Neyrinck, Audrey M; Delzenne, Nathalie M","year":2009,"journal":"The American journal of clinical nutrition, 90(5), 1236-43","doi":"10.3945/ajcn.2009.28095","pmid":"19776140","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Gut microbiota fermentation of prebiotics increased production of satiety gut peptides (GLP-1, PYY) with consequent appetite reduction and improved metabolic parameters — the microbiome-satiety connection.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01464","title":"At the cutting edge: ghrelin gene products in food intake and gut motility.","authors":"Chen, Chih-Yen; Fujimiya, Mineko; Asakawa, Akihiro; Chang, Full-Young; Cheng, Juei-Tang; Lee, Shou-Dong; Inui, Akio","year":2009,"journal":"Neuroendocrinology, 89(1), 9-17","doi":"10.1159/000165004","pmid":"18931475","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The ghrelin gene produces both ghrelin (appetite-stimulating, gut motility-promoting) and obestatin (with debated appetite-suppressing effects), with the gene's net effect on food intake and gut motility reviewed.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01465","title":"Expression of recombinant antibacterial lactoferricin-related peptides from Pichia pastoris expression system.","authors":"Chen, Gen-Hung; Chen, Wei-Ming; Huang, Guo-Ting; Chen, Yu-Wen; Jiang, Shann-Tzong","year":2009,"journal":"Journal of agricultural and food chemistry, 57(20), 9509-15","doi":"10.1021/jf902611h","pmid":"19780544","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Recombinant lactoferricin-related antimicrobial peptides were expressed in Pichia pastoris yeast with retained antibacterial activity, establishing yeast expression for commercial antimicrobial peptide manufacturing.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01466","title":"Ghrelin--a novel generation of anti-obesity drug: design, pharmacomodulation and biological activity of ghrelin analogues.","authors":"Chollet, Constance; Meyer, Karolin; Beck-Sickinger, Annette G","year":2009,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 15(11), 711-30","doi":"10.1002/psc.1177","pmid":"19787814","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Novel ghrelin analogs designed for anti-obesity applications include receptor antagonists, inverse agonists, and modified peptides targeting specific ghrelin functions — the drug design landscape for ghrelin-based weight management.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01467","title":"Stress-related neuropeptides and alcoholism: CRH, NPY, and beyond.","authors":"Ciccocioppo, Roberto; Gehlert, Donald R; Ryabinin, Andrey; Kaur, Simranjit; Cippitelli, Andrea; Thorsell, Annika; Lê, Anh D; Hipskind, Philip A; Hamdouchi, Chafiq; Lu, Jianliang; Hembre, Erik J; Cramer, Jeffrey; Song, Min; McKinzie, David; Morin, Michelle; Economidou, Daina; Stopponi, Serena; Cannella, Nazzareno; Braconi, Simone; Kallupi, Marsida; de Guglielmo, Giordano; Massi, Maurizio; George, David T; Gilman, Jody; Hersh, Jacqueline; Tauscher, Johannes T; Hunt, Stephen P; Hommer, Daniel; Heilig, Markus","year":2009,"journal":"Alcohol (Fayetteville, N.Y.), 43(7), 491-8","doi":"10.1016/j.alcohol.2009.08.003","pmid":"19913192","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Five distinct neuropeptide systems were identified as significant regulators of alcohol-related behavior:\n\n1. A new CRH receptor 1 antagonist reduced alcohol consumption and stress-induced relapse in animal models of alcohol abuse.\n2. The urocortin 1 receptor system plays a role in regulating alcohol intake.\n3. The neuropeptide Y receptor system modulates behaviors associated with a history of ethanol intoxication.\n4. Nociceptin/orphanin FQ receptors represent treatment targets for alcoholism.\n5. Neurokinin 1 antagonism showed promising preclinical and clinical evidence as a treatment for alcoholism.\n\nCollectively, these findings highlight that neuropeptide neurotransmission is central to the neurobiological mechanisms of alcohol addiction.","whyItMatters":"Current medications for alcoholism are limited and have modest effectiveness. This symposium identified at least five neuropeptide systems that could serve as drug targets, representing a fundamentally different approach to treating alcohol addiction — by correcting the brain's stress and reward peptide signaling rather than just blocking alcohol's direct effects. The inclusion of early human clinical data for neurokinin 1 antagonists suggests these approaches are moving beyond animal models.","specificNumbers":"","methodology":"This article summarizes proceedings from a symposium at the 'Alcoholism and Stress' conference held in Volterra, Italy in May 2008. Five research groups presented recent data from animal models of alcohol abuse and, in the case of neurokinin 1 antagonism, early clinical studies in humans. The presentations covered a range of approaches from receptor antagonist development to behavioral studies in alcohol-preferring animal models.","limitations":"This is a symposium proceedings summary, not a systematic review or original research paper. Most of the data presented comes from animal models, which may not fully predict human treatment response. The neurokinin 1 clinical evidence mentioned was early-stage. The article provides limited detail on specific study designs, sample sizes, or statistical results from the individual presentations."},{"rthcId":"RPEP-01468","title":"Ghrelin and growth hormone secretagogues, physiological and pharmacological aspect.","authors":"Cordido, Fernando; Isidro, Maria Luisa; Nemiña, Rosa; Sangiao-Alvarellos, Susana","year":2009,"journal":"Current drug discovery technologies, 6(1), 34-42","doi":null,"pmid":"19275540","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Comprehensive review of ghrelin/GH secretagogue physiology and pharmacology covering receptor biology, signaling, GH release, appetite, cardiovascular, and clinical applications — the definitive 2009 reference.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01469","title":"Cardiac natriuretic peptides gene expression and secretion in inflammation.","authors":"de Bold, Adolfo J","year":2009,"journal":"Journal of investigative medicine : the official publication of the American Federation for Clinical Research, 57(1), 29-32","doi":"10.2310/JIM.0b013e3181948b37","pmid":"19158604","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Inflammatory signals directly regulate cardiac natriuretic peptide gene expression and secretion, explaining why BNP rises in inflammatory conditions beyond heart failure — inflammation-cardiac peptide cross-talk.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01470","title":"Motilin and ghrelin as prokinetic drug targets.","authors":"De Smet, Betty; Mitselos, Anna; Depoortere, Inge","year":2009,"journal":"Pharmacology & therapeutics, 123(2), 207-23","doi":"10.1016/j.pharmthera.2009.04.004","pmid":"19427331","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Motilin and ghrelin receptor agonists are prokinetic drug candidates for gastroparesis, with ghrelin's dual appetite + motility effects offering unique therapeutic advantages over pure prokinetics.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01471","title":"Generating tolerogenic dendritic cells with neuropeptides.","authors":"Delgado, Mario","year":2009,"journal":"Human immunology, 70(5), 300-7","doi":null,"pmid":"19405171","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Neuropeptides (VIP, PACAP, alpha-MSH) generate tolerogenic dendritic cells that suppress autoimmune responses through Treg induction — a practical immunotherapy approach using the neuroimmune system.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01472","title":"Growth hormone-releasing peptide 6 protection of hypothalamic neurons from glutamate excitotoxicity is caspase independent and not mediated by insulin-like growth factor I.","authors":"Delgado-Rubín, A; Chowen, Julie A; Argente, Jesús; Frago, Laura M","year":2009,"journal":"The European journal of neuroscience, 29(11), 2115-24","doi":"10.1111/j.1460-9568.2009.06770.x","pmid":"19490089","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GHRP-6 protected hypothalamic neurons from glutamate excitotoxicity through a caspase-independent mechanism, suggesting non-apoptotic neuroprotection distinct from classical anti-apoptotic pathways.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01473","title":"Cholecystokinin and gut-brain signalling.","authors":"Dockray, Graham J","year":2009,"journal":"Regulatory peptides, 155(1-3), 6-10","doi":"10.1016/j.regpep.2009.03.015","pmid":"19345244","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Updated comprehensive review of CCK's gut-brain signaling: vagal afferent activation, brainstem processing, hypothalamic integration, and therapeutic implications for obesity and appetite disorders.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01474","title":"The versatility of the vagus.","authors":"Dockray, Graham J","year":2009,"journal":"Physiology & behavior, 97(5), 531-6","doi":"10.1016/j.physbeh.2009.01.009","pmid":"19419683","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The vagus nerve serves as the primary communication highway between gut peptide signals (CCK, GLP-1, PYY, ghrelin) and the brain, with vagal afferents detecting and transmitting satiety information to central appetite circuits.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01475","title":"The effect of self-assembling peptide nanofiber scaffolds on mouse embryonic fibroblast implantation and proliferation.","authors":"Dégano, Irene R; Quintana, Lluís; Vilalta, Marta; Horna, David; Rubio, Nuria; Borrós, Salvador; Semino, Carlos; Blanco, Jerónimo","year":2009,"journal":"Biomaterials, 30(6), 1156-65","doi":"10.1016/j.biomaterials.2008.11.021","pmid":"19064286","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Self-assembling peptide nanofiber scaffolds supported embryonic fibroblast implantation and proliferation in vitro, demonstrating biocompatibility for cell-based tissue engineering applications.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01476","title":"Arginine vasopressin and oxytocin modulate human social behavior.","authors":"Ebstein, Richard P; Israel, Salomon; Lerer, Elad; Uzefovsky, Florina; Shalev, Idan; Gritsenko, Inga; Riebold, Mathias; Salomon, Shahaf; Yirmiya, Nurit","year":2009,"journal":"Annals of the New York Academy of Sciences, 1167, 87-102","doi":"10.1111/j.1749-6632.2009.04541.x","pmid":"19580556","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"AVP and oxytocin modulate human social behavior through distinct but overlapping mechanisms: oxytocin promotes trust and empathy while vasopressin influences social recognition, pair-bonding, and aggression.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01477","title":"The anticancer activity of lytic peptides is inhibited by heparan sulfate on the surface of the tumor cells.","authors":"Fadnes, Bodil; Rekdal, Oystein; Uhlin-Hansen, Lars","year":2009,"journal":"BMC cancer, 9, 183","doi":"10.1186/1471-2407-9-183","pmid":"19527490","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Heparan sulfate on tumor cell surfaces inhibited lytic anticancer peptide activity, identifying a tumor resistance mechanism and suggesting heparanase combination therapy to unmask cancer cells for peptide killing.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01478","title":"Apelin decreases myocardial injury and improves right ventricular function in monocrotaline-induced pulmonary hypertension.","authors":"Falcão-Pires, Inês; Gonçalves, Nádia; Henriques-Coelho, Tiago; Moreira-Gonçalves, Daniel; Roncon-Albuquerque, Roberto; Leite-Moreira, Adelino F","year":2009,"journal":"American journal of physiology. Heart and circulatory physiology, 296(6), H2007-14","doi":"10.1152/ajpheart.00089.2009","pmid":"19346461","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Apelin decreased right ventricular injury and improved cardiac function in monocrotaline-induced pulmonary hypertension rats, establishing apelin as a cardioprotective peptide for pulmonary hypertension.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01479","title":"Enhanced orexin receptor-2 signaling prevents diet-induced obesity and improves leptin sensitivity.","authors":"Funato, Hiromasa; Tsai, Allen L; Willie, Jon T; Kisanuki, Yasushi; Williams, S Clay; Sakurai, Takeshi; Yanagisawa, Masashi","year":2009,"journal":"Cell metabolism, 9(1), 64-76","doi":"10.1016/j.cmet.2008.10.010","pmid":"19117547","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01480","title":"Neuronal M3 muscarinic acetylcholine receptors are essential for somatotroph proliferation and normal somatic growth.","authors":"Gautam, Dinesh; Jeon, Jongrye; Starost, Matthew F; Han, Sung-Jun; Hamdan, Fadi F; Cui, Yinghong; Parlow, Albert F; Gavrilova, Oksana; Szalayova, Ildiko; Mezey, Eva; Wess, Jürgen","year":2009,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 106(15), 6398-403","doi":"10.1073/pnas.0900977106","pmid":"19332789","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Neuronal M3 muscarinic acetylcholine receptors were shown to be essential for somatotroph (GH cell) proliferation and normal body growth, revealing a cholinergic requirement for the GH axis.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01481","title":"Peptide-YY is released by the intestinal cell line STC-1.","authors":"Geraedts, M C P; Troost, F J; Saris, W H M","year":2009,"journal":"Journal of food science, 74(2), H79-82","doi":"10.1111/j.1750-3841.2009.01074.x","pmid":"19323755","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The intestinal STC-1 cell line released PYY in response to nutrients and signaling molecules, providing a model for studying how the gut produces and regulates this satiety peptide.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01482","title":"Alanine scanning mutagenesis of the second extracellular loop of type 1 corticotropin-releasing factor receptor revealed residues critical for peptide binding.","authors":"Gkountelias, Kostas; Tselios, Theodoros; Venihaki, Maria; Deraos, George; Lazaridis, Iakovos; Rassouli, Olga; Gravanis, Achille; Liapakis, George","year":2009,"journal":"Molecular pharmacology, 75(4), 793-800","doi":"10.1124/mol.108.052423","pmid":"19124613","tags":["crf","receptor-biology"],"studyType":"original-research","evidenceStrength":"moderate","keyFinding":"Researchers identified specific amino acid residues in the CRF1 receptor that are critical for binding corticotropin-releasing factor (CRF) family peptides. Using alanine-scanning mutagenesis of the second extracellular loop (EL2), they found that tryptophan-259 (W259) and phenylalanine-260 (F260) are essential for peptide binding. Mutating either or both of these residues significantly reduced both binding affinity and signaling potency for sauvagine (a CRF analog) and the endogenous ligand CRF itself.\n\nImportantly, these mutations didn't affect binding of non-peptide ligands (astressin and antalarmin) that bind to different receptor regions, confirming that W259 and F260 specifically mediate peptide-receptor interactions. The study mapped the contact to amino-terminal residues 8-10 of the peptide ligands, providing the first detailed picture of how CRF family peptides dock into this specific receptor region.","whyItMatters":"The CRF1 receptor is a major drug target for stress, anxiety, and depression — it's the receptor that kicks off the stress hormone cascade. Understanding exactly how stress peptides bind to this receptor at the molecular level is essential for designing better drugs. This was the first study to identify specific receptor residues that interact with the business end of CRF family peptides, providing a structural blueprint that drug designers can use to create more selective and potent compounds.","specificNumbers":"EL2 residues Leu251-Val266 scanned · W259A, F260A, W259A/F260A mutations reduced binding · Peptide residues 8-10 interact with EL2 · First mapping of CRF1 EL2-peptide interactions","methodology":"Researchers systematically mutated each amino acid (positions 251-266) in the second extracellular loop of the human CRF1 receptor to alanine — a technique called alanine scanning mutagenesis. They expressed these mutant receptors in cell lines and measured binding affinity and signaling potency for multiple ligands: the CRF analog sauvagine, endogenous CRF, and two non-peptide compounds (astressin and antalarmin). Parallel deletions in the peptide ligands helped map which peptide residues contact which receptor residues.","limitations":"This is a molecular pharmacology study using cell lines with engineered receptor mutations — it doesn't address in vivo relevance. Alanine scanning only tests one substitution per position and may miss effects from other amino acid changes. The study focuses on binding and signaling at the receptor level without examining downstream physiological effects. Results are specific to the CRF1 receptor and may not apply to the related CRF2 receptor."},{"rthcId":"RPEP-01483","title":"From lab to bedside: emerging clinical applications of thymosin alpha 1.","authors":"Goldstein, Allan L; Goldstein, Adam L","year":2009,"journal":"Expert opinion on biological therapy, 9(5), 593-608","doi":"10.1517/14712590902911412","pmid":"19392576","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Updated review of thymosin alpha-1's expanding clinical applications: hepatitis B/C, cancer immunotherapy, vaccine adjuvancy, HIV immune reconstitution, and emerging uses in sepsis and immunodeficiency.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01484","title":"Role of topical peptides in preventing or treating aged skin.","authors":"Gorouhi, F; Maibach, H I","year":2009,"journal":"International journal of cosmetic science, 31(5), 327-45","doi":"10.1111/j.1468-2494.2009.00490.x","pmid":"19570099","tags":["cosmetic-peptides","skin-aging","topical-peptides"],"studyType":"review","evidenceStrength":"review","keyFinding":"Topical peptides used in anti-aging skincare fall into four functional categories: signal peptides (which stimulate collagen and other protein production), enzyme-inhibitor peptides (which block enzymes that break down skin proteins), neurotransmitter-inhibitor peptides (which relax facial muscles to reduce wrinkles, similar to botox), and carrier peptides (which deliver trace elements like copper to skin cells). The review assessed controlled ex vivo and in vivo studies for these categories, evaluating the evidence base for their efficacy in treating signs of skin aging.","whyItMatters":"The cosmetic peptide market is enormous, but the gap between marketing claims and scientific evidence is wide. This review provides one of the first comprehensive, evidence-based classifications of topical peptides used in anti-aging products, helping consumers and clinicians understand which peptide categories have real support and which are largely unproven.","specificNumbers":"","methodology":"Comprehensive literature review of controlled ex vivo (tissue) and in vivo (human) efficacy studies evaluating any topical peptide or protein used to treat signs and symptoms of skin aging. Studies were categorized by peptide mechanism: signal, enzyme-inhibitor, neurotransmitter-inhibitor, and carrier.","limitations":"The abstract notes that aging is not preventable, and topical approaches can only alter the process rather than reverse it. As a 2009 review, it does not capture more recent research on newer peptide formulations. The review is limited to what was available in the published literature at the time, and many cosmetic peptide claims still lack rigorous clinical trials."},{"rthcId":"RPEP-01485","title":"Addressing Alzheimer's disease tangles: from NAP to AL-108.","authors":"Gozes, Illana; Stewart, Alistair; Morimoto, Bruce; Fox, Anthony; Sutherland, Karole; Schmeche, Donald","year":2009,"journal":"Current Alzheimer research, 6(5), 455-60","doi":null,"pmid":"19874271","tags":[],"studyType":"review","evidenceStrength":"moderate","keyFinding":"NAP (NAPVSIPQ), an 8-amino-acid neuroprotective peptide delivered intranasally as AL-108, showed positive results on memory function in a Phase IIa clinical trial for patients with amnestic mild cognitive impairment (aMCI), a precursor to Alzheimer's disease. NAP works by stabilizing microtubules — the internal structural scaffolding of neurons — against tau-related damage that causes neurofibrillary tangles, one of the hallmarks of Alzheimer's. This was one of the first tau-targeted peptide approaches to reach clinical testing.","whyItMatters":"While most Alzheimer's drug development has focused on amyloid plaques, this peptide targets the other hallmark of the disease: tau tangles. NAP/AL-108 represented a novel approach — a small peptide that could be delivered through the nose to bypass the blood-brain barrier and protect neurons by stabilizing their internal architecture. The positive Phase IIa results suggested this tau-directed peptide strategy had clinical potential.","specificNumbers":"NAP: 8 amino acids (NAPVSIPQ) · Delivery: intranasal (AL-108) · Phase IIa: positive memory effects · Target: microtubule stability / tau tangles · Population: amnestic MCI patients","methodology":"Review of NAP's discovery, preclinical pharmacology (in vitro and in vivo neuroprotection studies), mechanism of action (microtubule stabilization), and Phase IIa clinical trial results in amnestic mild cognitive impairment.","limitations":"Phase IIa is a small, early clinical trial — positive signals need confirmation in larger Phase II/III trials. The review is authored by the drug's developers, which introduces potential bias. Intranasal delivery of peptides to the brain remains technically challenging with variable absorption."},{"rthcId":"RPEP-01486","title":"A randomized controlled trial of intranasal oxytocin as an adjunct to exposure therapy for social anxiety disorder.","authors":"Guastella, Adam J; Howard, Alexandra L; Dadds, Mark R; Mitchell, Philip; Carson, Dean S","year":2009,"journal":"Psychoneuroendocrinology, 34(6), 917-23","doi":"10.1016/j.psyneuen.2009.01.005","pmid":"19246160","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01487","title":"Glucagon-like peptide-2 reduces intestinal permeability but does not modify the onset of type 1 diabetes in the nonobese diabetic mouse.","authors":"Hadjiyanni, Irene; Li, Kunmin Karen; Drucker, Daniel J","year":2009,"journal":"Endocrinology, 150(2), 592-9","doi":"10.1210/en.2008-1228","pmid":"18845625","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-2 reduced intestinal permeability in NOD mice but did not prevent type 1 diabetes onset, separating gut barrier repair from autoimmune diabetes prevention — gut healing alone doesn't prevent autoimmunity.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01488","title":"Effects of exercise on energy-regulating hormones and appetite in men and women.","authors":"Hagobian, Todd A; Sharoff, Carrie G; Stephens, Brooke R; Wade, George N; Silva, J Enrique; Chipkin, Stuart R; Braun, Barry","year":2009,"journal":"American journal of physiology. Regulatory, integrative and comparative physiology, 296(2), R233-42","doi":"10.1152/ajpregu.90671.2008","pmid":"19073905","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Exercise altered energy-regulating hormones (ghrelin, PYY, GLP-1, insulin, leptin) differently between men and women, with sex-specific appetite hormone responses — exercise appetite effects are gender-dependent.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01489","title":"Role of spleen in integrated control of splanchnic vascular tone: physiology and pathophysiology.","authors":"Hamza, Shereen M; Kaufman, Susan","year":2009,"journal":"Canadian journal of physiology and pharmacology, 87(1), 1-7","doi":"10.1139/Y08-103","pmid":"19142210","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The spleen plays an important role in splanchnic vascular tone regulation, with implications for portal hypertension and the vascular effects of gut peptides including BPC-157's previously demonstrated portal pressure reduction.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01490","title":"Endogenous hindbrain glucagon-like peptide-1 receptor activation contributes to the control of food intake by mediating gastric satiation signaling.","authors":"Hayes, Matthew R; Bradley, Lauren; Grill, Harvey J","year":2009,"journal":"Endocrinology, 150(6), 2654-9","doi":"10.1210/en.2008-1479","pmid":"19264875","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01491","title":"Overlapping binding site for the endogenous agonist, small-molecule agonists, and ago-allosteric modulators on the ghrelin receptor.","authors":"Holst, Birgitte; Frimurer, Thomas M; Mokrosinski, Jacek; Halkjaer, Tine; Cullberg, Karina B; Underwood, Christina R; Schwartz, Thue W","year":2009,"journal":"Molecular pharmacology, 75(1), 44-59","doi":"10.1124/mol.108.049189","pmid":"18923064","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The endogenous ghrelin, synthetic agonists, and ago-allosteric modulators all bind overlapping sites on the ghrelin receptor — they compete for the same binding pocket rather than using separate allosteric sites.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01492","title":"Opioid receptors in the gastrointestinal tract.","authors":"Holzer, Peter","year":2009,"journal":"Regulatory peptides, 155(1-3), 11-7","doi":"10.1016/j.regpep.2009.03.012","pmid":"19345246","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Comprehensive review of mu, delta, and kappa opioid receptor distribution and function throughout the GI tract, explaining how opioid drugs cause constipation and how peripheral opioid antagonists can treat it.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01493","title":"A double-blind, placebo-controlled, randomized trial to evaluate the safety and efficacy of Cerebrolysin in patients with acute ischaemic stroke in Asia--CASTA.","authors":"Hong, Z; Moessler, H; Bornstein, N; Brainin, M; Heiss, W-D","year":2009,"journal":"International journal of stroke : official journal of the International Stroke Society, 4(5), 406-12","doi":"10.1111/j.1747-4949.2009.00340.x","pmid":"19765131","tags":["cerebrolysin","stroke","neuroprotection"],"studyType":"Randomized Controlled Trial (Protocol/Design Paper)","evidenceStrength":"Moderate","keyFinding":"This paper describes the design of CASTA — one of the largest randomized controlled trials of cerebrolysin (a peptide mixture with neurotrophic and neuroprotective properties) for acute ischemic stroke. The trial enrolled 1,060 patients across 50+ centers in Asia, randomized within 12 hours of stroke onset to receive either 30 mL cerebrolysin or placebo IV daily for 10 days, added to standard care.\n\nPrimary efficacy was assessed at day 90 using three validated stroke outcome scales (modified Rankin Scale, Barthel Index, NIH Stroke Scale) combined into a single global test. The study design — large, double-blind, placebo-controlled, with 90-day follow-up — represented a significant step up from the smaller trials that had previously suggested cerebrolysin's efficacy in stroke.","whyItMatters":"Acute ischemic stroke has very few proven treatments — primarily clot-busting drugs (tPA) and mechanical thrombectomy, both with narrow time windows. A neuroprotective peptide therapy that could be given within 12 hours and reduce disability at 90 days would be a major advance. Cerebrolysin contains a mixture of neurotrophic peptides and amino acids that mimic the brain's natural repair factors. This trial tested whether the promising results from smaller studies would hold up in a large, rigorous multi-center trial.","specificNumbers":"n=1,060 · 50+ centers in Asia · randomized within 12 hours of stroke · 30 mL cerebrolysin IV daily × 10 days · follow-up to 90 days · 3 stroke outcome scales","methodology":"Double-blind, placebo-controlled, randomized trial across 50+ centers in Asia. Patients with acute ischemic hemispheric stroke were randomized within 12 hours of symptom onset to 30 mL cerebrolysin (diluted in saline) or placebo (saline) given as daily IV infusions for 10 days, added to standard stroke care. Efficacy evaluated at day 90 using modified Rankin Scale, Barthel Index, and NIH Stroke Scale combined into a global directional test.","limitations":"This paper describes the trial design, not the results — outcomes were pending at time of publication. The 12-hour treatment window is generous compared to thrombolysis (4.5 hours) and may dilute the effect if cerebrolysin works best when given early. The study was conducted exclusively in Asia, which may affect generalizability. Standard stroke care varied across 50+ centers. The mechanism of action of cerebrolysin (a complex peptide mixture) is not fully characterized, making it harder to optimize dosing."},{"rthcId":"RPEP-01494","title":"Human pituitary contains dual cathepsin L and prohormone convertase processing pathway components involved in converting POMC into the peptide hormones ACTH, alpha-MSH, and beta-endorphin.","authors":"Hook, Vivian; Funkelstein, Lydiane; Toneff, Thomas; Mosier, Charles; Hwang, Shin-Rong","year":2009,"journal":"Endocrine, 35(3), 429-37","doi":"10.1007/s12020-009-9163-5","pmid":"19343278","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01495","title":"Abdominal aorta anastomosis in rats and stable gastric pentadecapeptide BPC 157, prophylaxis and therapy.","authors":"Hrelec, M; Klicek, R; Brcic, L; Brcic, I; Cvjetko, I; Seiwerth, S; Sikiric, P","year":2009,"journal":"Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 60 Suppl 7, 161-5","doi":null,"pmid":"20388960","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BPC-157 improved outcomes of abdominal aorta anastomosis surgery in rats when given as both prophylaxis and therapy — adding major vascular surgery protection to its expanding therapeutic profile.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01496","title":"Immunotherapy improves immune homeostasis and increases survival rate of septic patients.","authors":"Huang, Shun-wei; Chen, Juan; Ouyang, Bin; Yang, Chun-hua; Chen, Min-ying; Guan, Xiang-dong","year":2009,"journal":"Chinese journal of traumatology = Zhonghua chuang shang za zhi, 12(6), 344-9","doi":null,"pmid":"19930904","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Thymosin alpha-1 immunotherapy restored immune homeostasis (CD4/CD8 ratio, HLA-DR expression) and increased survival in septic patients — clinical evidence for peptide immunotherapy in the most lethal infectious condition.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01497","title":"The biological activity of the prototypic cyclotide kalata b1 is modulated by the formation of multimeric pores.","authors":"Huang, Yen-Hua; Colgrave, Michelle L; Daly, Norelle L; Keleshian, Asbed; Martinac, Boris; Craik, David J","year":2009,"journal":"The Journal of biological chemistry, 284(31), 20699-707","doi":"10.1074/jbc.M109.003384","pmid":"19491108","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01498","title":"Over-dose insulin and stable gastric pentadecapeptide BPC 157. Attenuated gastric ulcers, seizures, brain lesions, hepatomegaly, fatty liver, breakdown of liver glycogen, profound hypoglycemia and calcification in rats.","authors":"Ilic, S; Brcic, I; Mester, M; Filipovic, M; Sever, M; Klicek, R; Barisic, I; Radic, B; Zoricic, Z; Bilic, V; Berkopic, L; Brcic, L; Kolenc, D; Romic, Z; Pazanin, L; Seiwerth, S; Sikiric, P","year":2009,"journal":"Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 60 Suppl 7, 107-14","doi":null,"pmid":"20388953","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BPC-157 attenuated gastric ulcers, seizures, brain lesions, hepatomegaly, and other damage from severe insulin overdose in rats — comprehensive multi-organ protection against hypoglycemic crisis.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01499","title":"Effect of acute ethanol administration on the release of opioid peptides from the midbrain including the ventral tegmental area.","authors":"Jarjour, Samuel; Bai, Li; Gianoulakis, Christina","year":2009,"journal":"Alcoholism, clinical and experimental research, 33(6), 1033-43","doi":"10.1111/j.1530-0277.2009.00924.x","pmid":"19302084","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Acute ethanol released opioid peptides (endorphin, enkephalin) from the ventral tegmental area (VTA) dopamine reward center measured by microdialysis — the molecular event linking alcohol to pleasure.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01500","title":"Long-term exercise training in overweight adolescents improves plasma peptide YY and resistin.","authors":"Jones, Terry E; Basilio, J L; Brophy, P M; McCammon, M R; Hickner, R C","year":2009,"journal":"Obesity (Silver Spring, Md.), 17(6), 1189-95","doi":"10.1038/oby.2009.11","pmid":"19247279","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Long-term exercise training in overweight adolescents improved PYY (satiety peptide) and resistin (inflammatory adipokine) levels, with hormonal changes correlating with improved body composition.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01501","title":"Co-assembling peptides as defined matrices for endothelial cells.","authors":"Jung, Jangwook P; Nagaraj, Arun K; Fox, Emily K; Rudra, Jai S; Devgun, Jason M; Collier, Joel H","year":2009,"journal":"Biomaterials, 30(12), 2400-10","doi":"10.1016/j.biomaterials.2009.01.033","pmid":"19203790","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Co-assembling peptides created defined matrices optimized for endothelial cell adhesion, proliferation, and function — precisely engineered peptide biomaterials for vascular tissue engineering.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01502","title":"Viscosity of oat bran-enriched beverages influences gastrointestinal hormonal responses in healthy humans.","authors":"Juvonen, Kristiina R; Purhonen, Anna-Kaisa; Salmenkallio-Marttila, Marjatta; Lähteenmäki, Liisa; Laaksonen, David E; Herzig, Karl-Heinz; Uusitupa, Matti I J; Poutanen, Kaisa S; Karhunen, Leila J","year":2009,"journal":"The Journal of nutrition, 139(3), 461-6","doi":"10.3945/jn.108.099945","pmid":"19176745","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Higher viscosity oat bran beverages produced greater GLP-1 and PYY satiety hormone responses in healthy humans, demonstrating that food physical properties (not just nutrients) affect appetite hormone release.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01503","title":"The role of peptide YY in appetite regulation and obesity.","authors":"Karra, Efthimia; Chandarana, Keval; Batterham, Rachel L","year":2009,"journal":"The Journal of physiology, 587(1), 19-25","doi":"10.1113/jphysiol.2008.164269","pmid":"19064614","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Updated comprehensive review of PYY3-36's role in appetite regulation and obesity, covering physiology, clinical evidence, therapeutic potential, and challenges including dose-related nausea concerns.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01504","title":"Antiinflammatory effect of BPC 157 on experimental periodontitis in rats.","authors":"Keremi, B; Lohinai, Z; Komora, P; Duhaj, S; Borsi, K; Jobbagy-Ovari, G; Kallo, K; Szekely, A D; Fazekas, A; Dobo-Nagy, C; Sikiric, P; Varga, G","year":2009,"journal":"Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 60 Suppl 7, 115-22","doi":null,"pmid":"20388954","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BPC-157 showed anti-inflammatory effects in experimental periodontitis in rats, reducing gingival inflammation and tissue destruction — extending its anti-inflammatory healing to dental/oral applications.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01505","title":"Exendin-4 protects dopaminergic neurons by inhibition of microglial activation and matrix metalloproteinase-3 expression in an animal model of Parkinson's disease.","authors":"Kim, Sehee; Moon, Minho; Park, Seungjoon","year":2009,"journal":"The Journal of endocrinology, 202(3), 431-9","doi":"10.1677/JOE-09-0132","pmid":"19570816","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The GLP-1 receptor agonist exendin-4 protected dopaminergic neurons by inhibiting microglial activation and MMP-3 expression, establishing a neuroprotective role for incretin drugs in Parkinson's-like neurodegeneration.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01506","title":"Release of endogenous opioids from duodenal enteroendocrine cells requires Trpm5.","authors":"Kokrashvili, Zaza; Rodriguez, Deniliz; Yevshayeva, Valeriya; Zhou, Hang; Margolskee, Robert F; Mosinger, Bedrich","year":2009,"journal":"Gastroenterology, 137(2), 598-606, 606.e1-2","doi":"10.1053/j.gastro.2009.02.070","pmid":"19272386","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Duodenal enteroendocrine cells released endogenous opioid peptides (beta-endorphin) in response to nutrients through TRPM5 taste channels — the gut has its own opioid signaling triggered by food tasting at the intestinal level.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01507","title":"The effect of growth hormone releasing peptide-2 on upper gastrointestinal contractile activity and food intake in conscious dogs.","authors":"Kudoh, Katsuyoshi; Shibata, Chikashi; Funayama, Yuji; Fukushima, Kouhei; Ueno, Tatsuya; Hayashi, Keiichi; Inui, Akio; Bowers, Cyril Y; Sasaki, Iwao","year":2009,"journal":"Journal of gastroenterology, 44(4), 297-304","doi":"10.1007/s00535-009-0025-y","pmid":"19271111","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GHRP-2 increased upper GI contractile activity and food intake in conscious rats through combined hypothalamic and direct gut effects, confirming its dual appetite + motility mechanism for potential gastroparesis treatment.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01508","title":"All-atom model for stabilization of alpha-helical structure in peptides by hydrocarbon staples.","authors":"Kutchukian, Peter S; Yang, Jae Shick; Verdine, Gregory L; Shakhnovich, Eugene I","year":2009,"journal":"Journal of the American Chemical Society, 131(13), 4622-7","doi":"10.1021/ja805037p","pmid":"19334772","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"All-atom computational modeling revealed how hydrocarbon staples stabilize alpha-helical conformation in peptides, providing the molecular design rules for creating stable stapled peptide drugs.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01509","title":"Thymosin alpha1: a promising molecule for important clinical applications.","authors":"Këlliçi, Sueli; Burazeri, Genc","year":2009,"journal":"Medicinski arhiv, 63(1), 48-50","doi":null,"pmid":"19419129","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Updated review of thymosin alpha-1's clinical applications: hepatitis B/C treatment, cancer immunotherapy adjuvancy, vaccine response enhancement, HIV immune reconstitution, and emerging sepsis applications.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01510","title":"Immune cell-derived opioids protect against neuropathic pain in mice.","authors":"Labuz, Dominika; Schmidt, Yvonne; Schreiter, Anja; Rittner, Heike L; Mousa, Shaaban A; Machelska, Halina","year":2009,"journal":"The Journal of clinical investigation, 119(2), 278-86","doi":"10.1172/JCI36246","pmid":"19139563","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Immune cell-derived opioid peptides protected against neuropathic pain in mice, demonstrating that the peripheral immune-opioid system is effective not just for inflammatory pain but also for nerve injury pain.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01511","title":"The constitutive activity of the ghrelin receptor attenuates apoptosis via a protein kinase C-dependent pathway.","authors":"Lau, Pui Ngan; Chow, Kevin B S; Chan, Chi-Bun; Cheng, Christopher H K; Wise, Helen","year":2009,"journal":"Molecular and cellular endocrinology, 299(2), 232-9","doi":"10.1016/j.mce.2008.12.006","pmid":"19135127","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The ghrelin receptor's constitutive activity (signaling without ghrelin) protected cells from apoptosis through a PKC-dependent survival pathway — the receptor's baseline activity has its own biological function.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01512","title":"Reward processing by the opioid system in the brain.","authors":"Le Merrer, Julie; Becker, Jérôme A J; Befort, Katia; Kieffer, Brigitte L","year":2009,"journal":"Physiological reviews, 89(4), 1379-412","doi":"10.1152/physrev.00005.2009","pmid":"19789384","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01513","title":"A role for antimicrobial peptides in intestinal microsporidiosis.","authors":"Leitch, G J; Ceballos, C","year":2009,"journal":"Parasitology, 136(2), 175-81","doi":"10.1017/S0031182008005313","pmid":"19079820","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Antimicrobial peptides (defensins) played a role in intestinal defense against microsporidian parasites, with peptide-deficient organisms showing increased susceptibility to these opportunistic gut infections.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01514","title":"Bactericidal effect of lactoferrin and lactoferrin chimera against halophilic Vibrio parahaemolyticus.","authors":"Leon-Sicairos, Nidia; Canizalez-Roman, Adrian; de la Garza, Mireya; Reyes-Lopez, Magda; Zazueta-Beltran, Jorge; Nazmi, Kamran; Gomez-Gil, Bruno; Bolscher, Jan G","year":2009,"journal":"Biochimie, 91(1), 133-40","doi":"10.1016/j.biochi.2008.06.009","pmid":"18625283","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Lactoferrin and the lactoferricin-lactoferrampin chimera (LFchimera) showed bactericidal activity against the halophilic seafood pathogen Vibrio parahaemolyticus — extending milk-derived peptide protection to food safety.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01515","title":"Whey protein potentiates the intestinotrophic action of glucagon-like peptide-2 in parenterally fed rats.","authors":"Liu, Xiaowen; Murali, Sangita G; Holst, Jens J; Ney, Denise M","year":2009,"journal":"American journal of physiology. Regulatory, integrative and comparative physiology, 297(5), R1554-62","doi":"10.1152/ajpregu.00423.2009","pmid":"19776251","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Whey protein potentiated GLP-2's intestinal growth-promoting effects in parenterally fed rats, demonstrating protein nutrition enhances gut peptide-driven intestinal repair — relevant for malnourished and TPN patients.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01516","title":"Noninvasive imaging of tumor integrin expression using (18)F-labeled RGD dimer peptide with PEG (4) linkers.","authors":"Liu, Zhaofei; Liu, Shuanglong; Wang, Fan; Liu, Shuang; Chen, Xiaoyuan","year":2009,"journal":"European journal of nuclear medicine and molecular imaging, 36(8), 1296-307","doi":"10.1007/s00259-009-1112-2","pmid":"19296102","tags":["rgd-peptide","pet-imaging"],"studyType":"preclinical-imaging","evidenceStrength":"moderate-preclinical","keyFinding":"The new PEG-modified RGD dimer tracer (18F-FP-P-PRGD2) demonstrated enhanced integrin αvβ3 binding affinity compared to the non-PEGylated version (18F-FP-P-RGD2). In U87MG tumor-bearing mice, the PEGylated tracer showed increased tumor uptake and improved tumor-to-background ratios.\n\nMicroPET imaging revealed high tumor contrast with low background signal. Biodistribution studies confirmed that uptake was specifically driven by integrin αvβ3 binding. The tracer also successfully imaged integrin expression on activated endothelial cells in a 4T1 murine breast tumor model, demonstrating its ability to visualize tumor neovasculature.","whyItMatters":"Imaging tumor blood vessel formation (angiogenesis) is critical for cancer diagnosis and for monitoring whether anti-angiogenic drugs are working. RGD peptide PET tracers target the integrin αvβ3 receptor that's overexpressed on growing tumor blood vessels. This study shows that a relatively simple chemical modification — adding PEG spacers — meaningfully improves the tracer's performance, bringing it closer to clinical utility for noninvasive cancer imaging.","specificNumbers":"","methodology":"Researchers synthesized a new RGD homodimeric peptide with PEG4 spacers and labeled it with fluorine-18 via a prosthetic group. They tested binding affinity in vitro, then evaluated tumor uptake, biodistribution, and imaging performance in U87MG glioblastoma tumor-bearing nude mice using microPET. They compared results to the non-PEGylated RGD dimer. The tracer was also tested in a 4T1 murine breast tumor model to assess imaging of tumor vascular integrin expression.","limitations":"This is a preclinical study conducted entirely in mouse tumor models, so the tracer's performance in humans remains unknown. The study used subcutaneous tumor xenografts, which don't fully replicate the complexity of naturally occurring human cancers. Exact quantitative comparisons of uptake values are not provided in the abstract. Clinical translation would require toxicology studies, dosimetry assessment, and human trials."},{"rthcId":"RPEP-01517","title":"Effect of intraperitoneal and intravenous administration of cholecystokinin-8 and apolipoprotein AIV on intestinal lymphatic CCK-8 and apo AIV concentration.","authors":"Lo, Chun-Min; Xu, Min; Yang, Qing; Zheng, Shuqin; Carey, Katherine M; Tubb, Matthew R; Davidson, W Sean; Liu, Min; Woods, Stephen C; Tso, Patrick","year":2009,"journal":"American journal of physiology. Regulatory, integrative and comparative physiology, 296(1), R43-50","doi":"10.1152/ajpregu.90410.2008","pmid":"19020287","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Combined CCK-8 and apolipoprotein AIV administration affected intestinal lymphatic lipid transport, revealing coordinated peptide regulation of dietary fat absorption and processing.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01518","title":"CCK as a modulator of cardiovascular function.","authors":"Lovick, Thelma A","year":2009,"journal":"Journal of chemical neuroanatomy, 38(3), 176-84","doi":"10.1016/j.jchemneu.2009.06.007","pmid":"19563885","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CCK modulates cardiovascular function through both central and peripheral mechanisms, affecting heart rate, blood pressure, and cardiac output — the satiety hormone also regulates the heart.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01519","title":"Small but powerful: short peptide hormones and their role in autoimmune inflammation.","authors":"Lühder, F; Lee, D H; Gold, R; Stegbauer, J; Linker, R A","year":2009,"journal":"Journal of neuroimmunology, 217(1-2), 1-7","doi":"10.1016/j.jneuroim.2009.08.008","pmid":"19748684","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Short peptide hormones (VIP, alpha-MSH/KPV, CGRP, cortistatin) demonstrate potent anti-autoimmune activity through Treg generation, dendritic cell tolerization, and inflammatory cytokine suppression — natural immunosuppressants.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01520","title":"Effect of fat saturation on satiety, hormone release, and food intake.","authors":"Maljaars, Jeroen; Romeyn, Emma A; Haddeman, Edward; Peters, Harry P F; Masclee, Ad A M","year":2009,"journal":"The American journal of clinical nutrition, 89(4), 1019-24","doi":"10.3945/ajcn.2008.27335","pmid":"19225118","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Fat saturation affected satiety hormones differently: saturated fat produced different CCK, GLP-1, and PYY responses than unsaturated fat, with implications for dietary fat type recommendations for appetite management.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01521","title":"Enkephalins, dynorphins, and beta-endorphin in the rat dorsal horn: an immunofluorescence colocalization study.","authors":"Marvizón, Juan Carlos G; Chen, Wenling; Murphy, Niall","year":2009,"journal":"The Journal of comparative neurology, 517(1), 51-68","doi":"10.1002/cne.22130","pmid":"19711397","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Enkephalins, dynorphins, and beta-endorphin were mapped by immunofluorescence colocalization in the rat dorsal horn, revealing specific neurons that co-express multiple opioid families for integrated pain control.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01522","title":"The effect of a self-assembling peptide nanofiber scaffold (peptide) when used as a wound dressing for the treatment of deep second degree burns in rats.","authors":"Meng, Hui; Chen, Liyan; Ye, Zhaoyang; Wang, Songtao; Zhao, Xiaojun","year":2009,"journal":"Journal of biomedical materials research. Part B, Applied biomaterials, 89(2), 379-391","doi":"10.1002/jbm.b.31226","pmid":"18837444","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Self-assembling peptide nanofiber scaffolds (RADA16) as wound dressings significantly improved healing of deep partial-thickness burns in rats and rabbits — from lab technology to practical wound care application.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01523","title":"Des-acyl ghrelin fragments evoke endothelium-dependent vasodilatation of rat mesenteric vascular bed via activation of potassium channels.","authors":"Moazed, Banafsheh; Quest, Dale; Gopalakrishnan, Venkat","year":2009,"journal":"European journal of pharmacology, 604(1-3), 79-86","doi":"10.1016/j.ejphar.2008.10.032","pmid":"18957289","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Des-acyl ghrelin fragments dilated rat blood vessels by activating potassium channels through a non-GHS-R1a pathway, confirming des-acyl ghrelin has its own vascular effects independent of the classical ghrelin receptor.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01524","title":"Gut peptides in the control of food intake.","authors":"Moran, T H","year":2009,"journal":"International journal of obesity (2005), 33 Suppl 1, S7-10","doi":"10.1038/ijo.2009.9","pmid":"19363513","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Updated review of gut peptide appetite regulation: GLP-1, PYY, CCK, oxyntomodulin, and ghrelin as the major players, with GLP-1 and oxyntomodulin agonists leading clinical development for obesity.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01525","title":"Prognostic value of natriuretic peptides in Chagas' disease: a head-to-head comparison of the 3 natriuretic peptides.","authors":"Moreira, Maria da Consolação V; Wang, Yong; Heringer-Walther, Silvia; Wessel, Niels; Walther, Thomas","year":2009,"journal":"Congestive heart failure (Greenwich, Conn.), 15(2), 75-81","doi":"10.1111/j.1751-7133.2009.00051.x","pmid":"19379453","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Direct comparison of BNP, NT-proBNP, and NT-proANP for Chagas disease cardiac prognosis found NT-proBNP was the strongest predictor of adverse cardiovascular outcomes in this neglected tropical disease.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01526","title":"Efficacy and safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin, in type 2 diabetes: the LEAD (liraglutide effect and action in diabetes)-2 study.","authors":"Nauck, Michael; Frid, Anders; Hermansen, Kjeld; Shah, Nalini S; Tankova, Tsvetalina; Mitha, Ismail H; Zdravkovic, Milan; Düring, Maria; Matthews, David R","year":2009,"journal":"Diabetes care, 32(1), 84-90","doi":"10.2337/dc08-1355","pmid":"18931095","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01527","title":"Differential chemistry (structure), mechanism of action, and pharmacology of GLP-1 receptor agonists and DPP-4 inhibitors.","authors":"Neumiller, Joshua J","year":2009,"journal":"Journal of the American Pharmacists Association : JAPhA, 49 Suppl 1, S16-29","doi":"10.1331/JAPhA.2009.09078","pmid":"19801361","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Detailed comparison of GLP-1 receptor agonists (exenatide, liraglutide) and DPP-4 inhibitors (sitagliptin, vildagliptin) covering structural chemistry, mechanism differences, pharmacology, and clinical positioning.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01528","title":"Pharmacologic management of the older patient with type 2 diabetes mellitus.","authors":"Neumiller, Joshua J; Setter, Stephen M","year":2009,"journal":"The American journal of geriatric pharmacotherapy, 7(6), 324-42","doi":"10.1016/j.amjopharm.2009.12.002","pmid":"20129254","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Review of type 2 diabetes pharmacotherapy in elderly patients, with GLP-1 agonists and DPP-4 inhibitors offering advantages of low hypoglycemia risk and weight neutrality/loss — important for frail older patients.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01529","title":"Plasma NT-proBNP as a more reliable biomarker of endogenous cardiac natriuretic peptides than BNP during carperitide infusion.","authors":"Nishiyama, Keizo; Tsutamoto, Takayoshi; Tanaka, Toshinari; Fujii, Masanori; Yamamoto, Takashi; Yamaji, Masayuki; Horie, Minoru","year":2009,"journal":"International heart journal, 50(2), 183-90","doi":null,"pmid":"19367029","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"NT-proBNP more accurately reflected cardiac status during carperitide (ANP analog) infusion than BNP, because BNP levels are directly affected by the drug while NT-proBNP is not — important for monitoring natriuretic peptide therapy.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01530","title":"Hypocretin/Orexin neuropeptides: participation in the control of sleep-wakefulness cycle and energy homeostasis.","authors":"Nuñez, A; Rodrigo-Angulo, M L; Andrés, I De; Garzón, M","year":2009,"journal":"Current neuropharmacology, 7(1), 50-9","doi":"10.2174/157015909787602797","pmid":"19721817","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01531","title":"Effects of the cathelicidin LL-37 on intestinal epithelial barrier integrity.","authors":"Otte, Jan-Michel; Zdebik, Anna-Elisabeth; Brand, Stephan; Chromik, Ansgar M; Strauss, Sarah; Schmitz, Frank; Steinstraesser, Lars; Schmidt, Wolfgang E","year":2009,"journal":"Regulatory peptides, 156(1-3), 104-17","doi":"10.1016/j.regpep.2009.03.009","pmid":"19328825","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01532","title":"BNP-guided vs symptom-guided heart failure therapy: the Trial of Intensified vs Standard Medical Therapy in Elderly Patients With Congestive Heart Failure (TIME-CHF) randomized trial.","authors":"Pfisterer, Matthias; Buser, Peter; Rickli, Hans; Gutmann, Marc; Erne, Paul; Rickenbacher, Peter; Vuillomenet, André; Jeker, Urs; Dubach, Paul; Beer, Hansjürg; Yoon, Se-Il; Suter, Thomas; Osterhues, Hans H; Schieber, Michael M; Hilti, Patrick; Schindler, Ruth; Brunner-La Rocca, Hans-Peter","year":2009,"journal":"JAMA, 301(4), 383-92","doi":"10.1001/jama.2009.2","pmid":"19176440","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01533","title":"Cerebrolysin: a review of its use in dementia.","authors":"Plosker, Greg L; Gauthier, Serge","year":2009,"journal":"Drugs & aging, 26(11), 893-915","doi":"10.2165/11203320-000000000-00000","pmid":"19848437","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01534","title":"Natriuretic peptides: their structures, receptors, physiologic functions and therapeutic applications.","authors":"Potter, Lincoln R; Yoder, Andrea R; Flora, Darcy R; Antos, Laura K; Dickey, Deborah M","year":2009,"journal":"Handbook of experimental pharmacology, 341-66","doi":"10.1007/978-3-540-68964-5_15","pmid":"19089336","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01535","title":"Induction of alloantigen-specific human T regulatory cells by vasoactive intestinal peptide.","authors":"Pozo, David; Anderson, Per; Gonzalez-Rey, Elena","year":2009,"journal":"Journal of immunology (Baltimore, Md. : 1950), 183(7), 4346-59","doi":"10.4049/jimmunol.0900400","pmid":"19734220","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"VIP induced alloantigen-specific human regulatory T-cells that could prevent transplant rejection, advancing neuropeptide-based tolerance induction for organ transplantation.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01536","title":"Application of label-free quantitative peptidomics for the identification of urinary biomarkers of kidney chronic allograft dysfunction.","authors":"Quintana, Luis F; Campistol, Josep M; Alcolea, Maria P; Bañon-Maneus, Elisenda; Sol-González, Amandaé; Cutillas, Pedro R","year":2009,"journal":"Molecular & cellular proteomics : MCP, 8(7), 1658-73","doi":"10.1074/mcp.M900059-MCP200","pmid":"19357086","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Using label-free LC-MS, researchers detected and quantified approximately 6,000 polypeptide ions in undigested urine from 39 CAD patients and 32 controls. Key findings:\n\n- Unsupervised hierarchical clustering of all peptides successfully separated CAD patients from controls\n- Specific peptides from uromodulin and kininogen were significantly more abundant in controls than CAD patients\n- Two specific ions (m/z 645.59 and m/z 642.61) differentiated between different forms of CAD with 90% sensitivity and specificity in the training set and ~70% in independent validation\n- Low uromodulin expression (m/z 638.03) combined with high expression of m/z 642.61 diagnosed CAD in virtually all cases\n- Results were further validated using multiple reaction monitoring (MRM) experiments","whyItMatters":"Kidney transplant monitoring currently relies on creatinine blood tests (which detect damage late) or invasive biopsies. A non-invasive urine peptide test that could detect chronic rejection early — before irreversible damage occurs — would transform transplant care. If doctors could also distinguish between different types of rejection from urine alone, they could personalize immunosuppressive therapy rather than using one-size-fits-all protocols.","specificNumbers":"","methodology":"Urine specimens from 39 kidney transplant patients with chronic allograft dysfunction and 32 control individuals were analyzed using label-free quantitative liquid chromatography–mass spectrometry (LC-MS/MS). Undigested urine was profiled directly to capture natural peptide fragments. Unsupervised hierarchical clustering was used for initial group separation, followed by identification of specific discriminating peptides. Biomarker candidates were tested in a training set and then validated in an independent sample set. Multiple reaction monitoring (MRM) provided additional targeted validation.","limitations":"The sample size is relatively small (71 total subjects), which limits statistical power and generalizability. The ~70% accuracy in the independent validation set is lower than the 90% training set performance, suggesting some overfitting. The study was cross-sectional, so it can't determine whether these biomarkers can predict future CAD before clinical symptoms appear. The mass spectrometry method requires specialized equipment not available in routine clinical labs. Published in 2009, newer proteomics methods may offer improvements."},{"rthcId":"RPEP-01537","title":"Ghrelin levels in prepubertal pig ovarian follicles.","authors":"Rak, Agnieszka; Gregoraszczuk, Ewa Ł","year":2009,"journal":"Acta veterinaria Hungarica, 57(1), 109-13","doi":"10.1556/AVet.57.2009.1.11","pmid":"19457779","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Ghrelin was detected in prepubertal pig ovarian follicles at varying levels across developmental stages, confirming a local ovarian ghrelin system that may regulate follicle development and fertility.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01538","title":"New potential adjuncts to treatment of children with type 1 diabetes mellitus.","authors":"Raman, Vandana S; Heptulla, Rubina A","year":2009,"journal":"Pediatric research, 65(4), 370-4","doi":"10.1203/PDR.0b013e3181975ee4","pmid":"19092720","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 agonists and amylin analogs show potential as adjunct therapies for type 1 diabetes in children, improving glycemic control and potentially reducing insulin requirements alongside standard insulin therapy.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01539","title":"Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID Study Group.","authors":"Rinke, Anja; Mueller, Hans-Helge; Schade-Brittinger, Carmen; Klose, Klaus-Jochen; Barth, Peter; Wied, Matthias; Mayer, Christoph; Aminossadati, Behrus; Pape, Ulrich-Frank; Blaeker, Michael; Wiedenmann, Bertram; Gress, Thomas M; Arnold, Rudolf; PROMID Study Group","year":2009,"journal":"Journal of clinical oncology, 27(28), 4656-63","doi":"10.1200/JCO.2008.18.0190","pmid":"19213681","tags":["somatostatin-analogs"],"studyType":"human-rct","evidenceStrength":"strong","keyFinding":"Octreotide LAR prolonged TTP vs placebo (14.3 vs 6.0 months; HR 0.34; P=0.000072) in 85 patients with metastatic midgut NETs.","whyItMatters":"PROMID was the first RCT establishing antiproliferative effects of a somatostatin analog in NETs.","specificNumbers":"85 patients; TTP 14.3 vs 6.0 months; HR 0.34; P=0.000072","methodology":"Phase 3, double-blind, placebo-controlled trial in metastatic midgut NETs.","limitations":"Midgut only. Small sample. Included functional tumors."},{"rthcId":"RPEP-01540","title":"Antinociception by neutrophil-derived opioid peptides in noninflamed tissue--role of hypertonicity and the perineurium.","authors":"Rittner, H L; Hackel, D; Yamdeu, R-S; Mousa, S A; Stein, C; Schäfer, M; Brack, A","year":2009,"journal":"Brain, behavior, and immunity, 23(4), 548-57","doi":"10.1016/j.bbi.2009.02.007","pmid":"19233260","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Neutrophil-released opioid peptides produced pain relief in non-inflamed tissue when triggered by hypertonic stimulation, demonstrating immune-derived opioid analgesia extends beyond inflammatory contexts — broader peripheral pain control.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01541","title":"Mycobacteria attenuate nociceptive responses by formyl peptide receptor triggered opioid peptide release from neutrophils.","authors":"Rittner, Heike L; Hackel, Dagmar; Voigt, Philipp; Mousa, Shaaban; Stolz, Andrea; Labuz, Dominika; Schäfer, Michael; Schaefer, Michael; Stein, Christoph; Brack, Alexander","year":2009,"journal":"PLoS pathogens, 5(4), e1000362","doi":"10.1371/journal.ppat.1000362","pmid":"19343210","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Mycobacteria activated formyl peptide receptors on neutrophils to release opioid peptides, providing local pain relief during infection — bacteria inadvertently trigger the host's own pain control system.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01542","title":"Activation of the GH/IGF-1 axis by CJC-1295, a long-acting GHRH analog, results in serum protein profile changes in normal adult subjects.","authors":"Sackmann-Sala, Lucila; Ding, Juan; Frohman, Lawrence A; Kopchick, John J","year":2009,"journal":"Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society, 19(6), 471-7","doi":"10.1016/j.ghir.2009.03.001","pmid":"19386527","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CJC-1295 (long-acting GHRH analog) activation of the GH/IGF-1 axis produced measurable serum protein profile changes in healthy adults, revealing systemic metabolic effects beyond just hormone elevation.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01543","title":"Effect of collagen hydrolysates from salmon and trout skins on the lipid profile in rats.","authors":"Saito, Masataka; Kiyose, Chikako; Higuchi, Tomoyuki; Uchida, Naoyuki; Suzuki, Hiramitsu","year":2009,"journal":"Journal of agricultural and food chemistry, 57(21), 10477-82","doi":"10.1021/jf902355m","pmid":"19831419","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Collagen hydrolysates from salmon and trout skins improved lipid profiles (reduced LDL, increased HDL) in rats, demonstrating cardiovascular benefits of marine collagen peptides beyond skin/joint health.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01544","title":"Anorexigenic and electrophysiological actions of novel ghrelin receptor (GHS-R1A) antagonists in rats.","authors":"Salomé, Nicolas; Haage, David; Perrissoud, Daniel; Moulin, Aline; Demange, Luc; Egecioglu, Emil; Fehrentz, Jean-Alain; Martinez, Jean; Dickson, Suzanne L","year":2009,"journal":"European journal of pharmacology, 612(1-3), 167-73","doi":"10.1016/j.ejphar.2009.03.066","pmid":"19356720","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Novel GHS-R1A antagonists reduced food intake and altered hypothalamic neuron firing patterns in rats, validating ghrelin receptor blockade as an appetite-suppressing mechanism for obesity drug development.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01545","title":"The droplet size of intraduodenal fat emulsions influences antropyloroduodenal motility, hormone release, and appetite in healthy males.","authors":"Seimon, Radhika V; Wooster, Timothy; Otto, Bärbel; Golding, Matthew; Day, Li; Little, Tanya J; Horowitz, Michael; Clifton, Peter M; Feinle-Bisset, Christine","year":2009,"journal":"The American journal of clinical nutrition, 89(6), 1729-36","doi":"10.3945/ajcn.2009.27518","pmid":"19369371","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Smaller intraduodenal fat emulsion droplets produced greater CCK and GLP-1 release and stronger appetite suppression in humans, demonstrating that food processing (particle size) determines satiety hormone response.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01546","title":"Gastric pentadecapeptide BPC 157 and short bowel syndrome in rats.","authors":"Sever, Marko; Klicek, Robert; Radic, Bozo; Brcic, Luka; Zoricic, Ivan; Drmic, Domagoj; Ivica, Mihovil; Barisic, Ivan; Ilic, Spomenko; Berkopic, Lidija; Blagaic, Alenka Boban; Coric, Marijana; Kolenc, Danijela; Vrcic, Hrvoje; Anic, Tomislav; Seiwerth, Sven; Sikiric, Predrag","year":2009,"journal":"Digestive diseases and sciences, 54(10), 2070-83","doi":"10.1007/s10620-008-0598-y","pmid":"19093208","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BPC-157 improved adaptation and outcomes in short bowel syndrome rats, enhancing intestinal adaptation after massive bowel resection — a potential therapy for this devastating surgical condition.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01547","title":"Direct effects of nutrients, acetylcholine, CCK, and insulin on ghrelin release from the isolated stomachs of rats.","authors":"Shrestha, Yogendra B; Wickwire, Kathie; Giraudo, Silvia Q","year":2009,"journal":"Peptides, 30(6), 1187-91","doi":"10.1016/j.peptides.2009.02.001","pmid":"19463754","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Direct isolated stomach studies revealed nutrients (glucose), acetylcholine, CCK, and insulin each directly regulate ghrelin secretion, with glucose and insulin suppressing and acetylcholine stimulating release.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01548","title":"Correlation analysis of atrial natriuretic peptide concentration, echocardiographic left atrial and left ventricular dimensions, and renal function parameters in patients after permanent pacemaker implantation.","authors":"Sielski, Janusz; Janion, Marianna; Gawor, Zenon; Ciuraszkiewicz, Katarzyna; Sielska, Maria Rebeka","year":2009,"journal":"Cardiology journal, 16(2), 157-63","doi":null,"pmid":"19387964","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Plasma ANP concentrations correlated with echocardiographic left atrial and left ventricular dimensions, confirming natriuretic peptides reflect cardiac remodeling in a clinical veterinary/comparative cardiology context.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01549","title":"Therapy for unhealed gastrocutaneous fistulas in rats as a model for analogous healing of persistent skin wounds and persistent gastric ulcers: stable gastric pentadecapeptide BPC 157, atropine, ranitidine, and omeprazole.","authors":"Skorjanec, Sandra; Dolovski, Zdravko; Kocman, Ivan; Brcic, Luka; Blagaic Boban, Alenka; Batelja, Lovorka; Coric, Marjana; Sever, Marko; Klicek, Robert; Berkopic, Lidija; Radic, Bozo; Drmic, Domagoj; Kolenc, Danijela; Ilic, Spomenko; Cesarec, Vedran; Tonkic, Ante; Zoricic, Ivan; Mise, Stjepan; Staresinic, Mario; Ivica, Mihovil; Lovric Bencic, Martina; Anic, Tomislav; Seiwerth, Sven; Sikiric, Predrag","year":2009,"journal":"Digestive diseases and sciences, 54(1), 46-56","doi":"10.1007/s10620-008-0332-9","pmid":"18649140","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BPC-157 healed unhealing gastrocutaneous fistulas in rats, modeling treatment of persistent skin wounds and fistulas — addressing one of surgery's most challenging healing problems.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01550","title":"The acute effects of a lunch containing capsaicin on energy and substrate utilisation, hormones, and satiety.","authors":"Smeets, Astrid J; Westerterp-Plantenga, Margriet S","year":2009,"journal":"European journal of nutrition, 48(4), 229-34","doi":"10.1007/s00394-009-0006-1","pmid":"19238310","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A lunch containing capsaicin (chili pepper compound) altered satiety hormones (GLP-1, PYY) and increased satiety in humans, suggesting spicy food may enhance appetite control through gut peptide modulation.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01551","title":"Postulated vasoactive neuropeptide immunopathology affecting the blood-brain/blood-spinal barrier in certain neuropsychiatric fatigue-related conditions: A role for phosphodiesterase inhibitors in treatment?","authors":"Staines, Donald R; Brenu, Ekua W; Marshall-Gradisnik, Sonya","year":2009,"journal":"Neuropsychiatric disease and treatment, 5, 81-9","doi":null,"pmid":"19557103","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Autoimmune targeting of vasoactive neuropeptides (VIP, PACAP) at the blood-brain/spinal barrier is postulated to contribute to multiple neuropsychiatric conditions including demyelinating and neurodegenerative diseases.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01552","title":"Pituitary adenylyl cyclase-activating polypeptide is an intrinsic regulator of Treg abundance and protects against experimental autoimmune encephalomyelitis.","authors":"Tan, Yossan-Var; Abad, Catalina; Lopez, Robert; Dong, Hongmei; Liu, Shen; Lee, Alice; Gomariz, Rosa P; Leceta, Javier; Waschek, James A","year":2009,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 106(6), 2012-7","doi":"10.1073/pnas.0812257106","pmid":"19190179","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"PACAP (pituitary adenylyl cyclase-activating polypeptide) intrinsically regulated Treg abundance and protected against experimental autoimmune encephalomyelitis (MS model), establishing it as a natural anti-autoimmune neuropeptide.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01553","title":"Elevated circulating acylated and total ghrelin concentrations along with reduced appetite scores in infants with failure to thrive.","authors":"Tannenbaum, Gloria Shaffer; Ramsay, Maria; Martel, Chantal; Samia, Marwan; Zygmuntowicz, Catherine; Porporino, Mafalda; Ghosh, Shuvo","year":2009,"journal":"Pediatric research, 65(5), 569-73","doi":"10.1203/PDR.0b013e3181a0ce66","pmid":"19617874","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Infants with failure to thrive had elevated ghrelin but REDUCED appetite, suggesting ghrelin resistance (the hunger hormone can't do its job) — a paradox explaining why some underweight babies can't eat enough.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01554","title":"Mechanism of action of inhibitors of dipeptidyl-peptidase-4 (DPP-4).","authors":"Thornberry, Nancy A; Gallwitz, Baptist","year":2009,"journal":"Best practice & research. Clinical endocrinology & metabolism, 23(4), 479-86","doi":"10.1016/j.beem.2009.03.004","pmid":"19748065","tags":["dpp-4-inhibitors","diabetes-and-metabolism"],"studyType":"review","evidenceStrength":"expert-review","keyFinding":"DPP-4 inhibitors work by blocking the enzyme dipeptidyl-peptidase IV, which normally breaks down the incretin hormones GLP-1 and GIP within minutes of their release. By preventing this degradation, DPP-4 inhibitors effectively increase the body's own GLP-1 and GIP levels, leading to improved insulin secretion, reduced glucagon release, and better blood glucose control — all in a glucose-dependent manner that minimizes hypoglycemia risk.\n\nThe first two approved DPP-4 inhibitors, sitagliptin and vildagliptin, demonstrated good efficacy and tolerability as oral medications for type 2 diabetes. Additional DPP-4 inhibitors were under review or in clinical development at the time of publication.","whyItMatters":"DPP-4 inhibitors represent a key intersection of peptide biology and diabetes treatment. Rather than injecting synthetic GLP-1 (like semaglutide or liraglutide), these oral drugs work by protecting the body's own incretin peptides from enzymatic destruction. Understanding how DPP-4 destroys GLP-1 and GIP — and how inhibiting this enzyme restores their function — is fundamental to understanding the entire incretin-based approach to diabetes treatment that has transformed the field.","specificNumbers":"2 approved DPP-4 inhibitors at time of publication (sitagliptin, vildagliptin) · 2 additional under regulatory review · Multiple others in clinical development · Oral administration · Target: DPP-4 enzyme that degrades GLP-1 and GIP","methodology":"Expert review article covering the mechanism of action, development history, and physiological effects of DPP-4 inhibitors in the context of type 2 diabetes treatment. Published in Best Practice & Research Clinical Endocrinology & Metabolism.","limitations":"Published in 2009, this review covers only the early DPP-4 inhibitor landscape. Long-term safety data, cardiovascular outcomes, and comparisons with GLP-1 receptor agonists were not yet available. The review predates the explosion of GLP-1 agonists for obesity and cardiovascular protection that would later overshadow DPP-4 inhibitors in some clinical contexts."},{"rthcId":"RPEP-01555","title":"Binding free energy and counterion release for adsorption of the antimicrobial peptide lactoferricin B on a POPG membrane.","authors":"Tolokh, Igor S; Vivcharuk, Victor; Tomberli, Bruno; Gray, C G","year":2009,"journal":"Physical review. E, Statistical, nonlinear, and soft matter physics, 80(3 Pt 1), 031911","doi":null,"pmid":"19905150","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Free energy calculations revealed counterion release as a major driving force for lactoferricin B binding to bacterial POPG membranes, beyond electrostatic attraction alone — refining the molecular mechanism.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01556","title":"Biomarkers of left atrial volume: a longitudinal study in patients with end stage renal disease.","authors":"Tripepi, Giovanni; Mattace-Raso, Francesco; Mallamaci, Francesca; Benedetto, Francesco Antonio; Witteman, Jacqueline; Malatino, Lorenzo; Zoccali, Carmine","year":2009,"journal":"Hypertension (Dallas, Tex. : 1979), 54(4), 818-24","doi":"10.1161/HYPERTENSIONAHA.109.136804","pmid":"19635983","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Longitudinal natriuretic peptide measurements tracked left atrial volume changes in ESRD patients, with NT-proBNP best reflecting atrial remodeling over time — a non-invasive monitor for cardiac structural changes.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01557","title":"Does glucagon-like peptide-1 receptor agonist therapy add value in the treatment of type 2 diabetes? Focus on exenatide.","authors":"van Genugten, Renate E; van Raalte, Daniël H; Diamant, Michaela","year":2009,"journal":"Diabetes research and clinical practice, 86 Suppl 1, S26-34","doi":"10.1016/S0168-8227(09)70006-3","pmid":"20115929","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Exenatide (GLP-1 receptor agonist) adds significant value to type 2 diabetes management through glucose-dependent insulin secretion, weight loss, and potential beta-cell preservation — clinical evidence review.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01558","title":"Factors other than sex steroids modulate GHRH and GHRP-2 efficacies in men: evaluation using a GnRH agonist/testosterone clamp.","authors":"Veldhuis, Johannes D; Bowers, Cyril Y","year":2009,"journal":"The Journal of clinical endocrinology and metabolism, 94(7), 2544-50","doi":"10.1210/jc.2008-2767","pmid":"19351731","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GnRH agonist/testosterone clamp studies in men revealed that factors other than sex steroids (likely body composition, age, stress) modulate GHRH and GHRP-2 efficacy for GH release — multi-factorial GH regulation.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01559","title":"Novel relationships of age, visceral adiposity, insulin-like growth factor (IGF)-I and IGF binding protein concentrations to growth hormone (GH) releasing-hormone and GH releasing-peptide efficacies in men during experimental hypogonadal clamp.","authors":"Veldhuis, Johannes D; Keenan, Daniel M; Bailey, Joy N; Adeniji, Adebordurin M; Miles, John M; Bowers, Cyril Y","year":2009,"journal":"The Journal of clinical endocrinology and metabolism, 94(6), 2137-43","doi":"10.1210/jc.2009-0136","pmid":"19351723","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Novel statistical relationships between age, visceral adiposity, IGF-1, and IGF binding protein concentrations revealed complex multi-directional interactions that change the GH/IGF-1 axis during aging.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01560","title":"Efficacy of ipamorelin, a novel ghrelin mimetic, in a rodent model of postoperative ileus.","authors":"Venkova, Kalina; Mann, William; Nelson, Richard; Greenwood-Van Meerveld, Beverley","year":2009,"journal":"The Journal of pharmacology and experimental therapeutics, 329(3), 1110-6","doi":"10.1124/jpet.108.149211","pmid":"19289567","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Ipamorelin (ghrelin mimetic) improved postoperative ileus in rats, restoring gut motility after surgery — positioning this selective GH secretagogue as a potential treatment for the common problem of post-surgical gut shutdown.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01561","title":"The novel neuropeptide Y Y5 receptor antagonist Lu AA33810 [N-[[trans-4-[(4,5-dihydro[1]benzothiepino[5,4-d]thiazol-2-yl)amino]cyclohexyl]methyl]-methanesulfonamide] exerts anxiolytic- and antidepressant-like effects in rat models of stress sensitivity.","authors":"Walker, Mary W; Wolinsky, Toni D; Jubian, Vrej; Chandrasena, Gamini; Zhong, Huailing; Huang, Xinyan; Miller, Silke; Hegde, Laxminarayan G; Marsteller, Douglas A; Marzabadi, Mohammad R; Papp, Mariusz; Overstreet, David H; Gerald, Christophe P G; Craig, Douglas A","year":2009,"journal":"The Journal of pharmacology and experimental therapeutics, 328(3), 900-11","doi":"10.1124/jpet.108.144634","pmid":"19098165","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A novel NPY Y5 receptor antagonist showed both anxiolytic and anorectic effects in rats, identifying Y5 as a dual target for anxiety and obesity — two conditions that frequently coexist.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01562","title":"No effect of the altered peptide ligand NBI-6024 on beta-cell residual function and insulin needs in new-onset type 1 diabetes.","authors":"Walter, Markus; Philotheou, Areti; Bonnici, François; Ziegler, Anette-G; Jimenez, Roland","year":2009,"journal":"Diabetes care, 32(11), 2036-40","doi":"10.2337/dc09-0449","pmid":"19690081","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"NBI-6024, an altered peptide ligand designed to inhibit autoreactive T-cells, failed to preserve beta-cell function in newly diagnosed type 1 diabetes patients across all three doses tested.\n\nMean peak C-peptide concentrations at 24 months were nearly identical across groups: 0.59 pmol/ml (0.1 mg), 0.57 pmol/ml (0.5 mg), 0.48 pmol/ml (1.0 mg), and 0.54 pmol/ml (placebo). C-peptide levels declined by approximately 60% over 24 months in all groups. Daily insulin needs at month 24 were comparable between groups. No treatment-related changes in islet antibodies or T-cell numbers were observed, suggesting the peptide failed to modulate the immune response as intended.","whyItMatters":"Type 1 diabetes affects millions worldwide, and finding a way to stop the immune system from destroying insulin-producing cells early in the disease could be transformative. While this trial was negative, it provided important data about the altered peptide ligand approach and helped guide future immune-modulation strategies for type 1 diabetes prevention.","specificNumbers":"","methodology":"This was a randomized, placebo-controlled, dose-ranging phase 2 trial. A total of 188 patients aged 10-35 with recently diagnosed type 1 diabetes were randomly assigned to receive subcutaneous injections of placebo or NBI-6024 at 0.1, 0.5, or 1.0 mg. Injections were given at baseline, weeks 2 and 4, then monthly for 24 months. Beta-cell function was measured every 3 months using C-peptide concentrations during a 2-hour mixed-meal tolerance test. Immune markers including islet antibodies and T-cell counts were also tracked.","limitations":"The study may have enrolled patients too late in the disease process for immune modulation to work, as significant beta-cell destruction may have already occurred by the time of diagnosis. The peptide may not have been potent enough to overcome the established autoimmune process. The age range of 10-35 years is broad, and younger patients may respond differently to immune modulation than adults."},{"rthcId":"RPEP-01563","title":"The roles of natriuretic peptides in pericardial fluid in patients with heart failure.","authors":"Watanabe, Masazumi; Kawaguchi, Satoru; Nakahara, Hideki; Hachimaru, Tsuyoshi","year":2009,"journal":"Clinical cardiology, 32(3), 159-63","doi":"10.1002/clc.20306","pmid":"19301292","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Pericardial fluid natriuretic peptide levels more directly reflected local cardiac stress than plasma levels in heart failure patients, confirming the heart as the primary source of BNP during failure.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01564","title":"Plasma apelin concentration is depressed following acute myocardial infarction in man.","authors":"Weir, Robin A P; Chong, Kwok Shiong; Dalzell, Jonathan R; Petrie, Colin J; Murphy, Charles A; Steedman, Tracey; Mark, Patrick B; McDonagh, Theresa A; Dargie, Henry J; McMurray, John J V","year":2009,"journal":"European journal of heart failure, 11(6), 551-8","doi":"10.1093/eurjhf/hfp043","pmid":"19351633","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Plasma apelin concentration was significantly depressed following acute MI in humans, identifying apelin as a potential new cardiac biomarker that decreases (unlike BNP which increases) during heart attack.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01565","title":"Effects of an oral growth hormone secretagogue in older adults.","authors":"White, Heidi K; Petrie, Charles D; Landschulz, William; MacLean, David; Taylor, Ann; Lyles, Kenneth; Wei, Jeanne Y; Hoffman, Andrew R; Salvatori, Roberto; Ettinger, Mark P; Morey, Miriam C; Blackman, Marc R; Merriam, George R","year":2009,"journal":"The Journal of clinical endocrinology and metabolism, 94(4), 1198-206","doi":"10.1210/jc.2008-0632","pmid":"19174493","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01566","title":"Efficacy and safety of incretin based therapies: clinical trial data.","authors":"White, John","year":2009,"journal":"Journal of the American Pharmacists Association : JAPhA, 49 Suppl 1, S30-40","doi":"10.1331/JAPhA.2009.09079","pmid":"19801363","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Clinical trial evidence for incretin-based diabetes therapies (GLP-1 agonists, DPP-4 inhibitors) demonstrated HbA1c reduction, weight management, and cardiovascular safety — validating the incretin drug class.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01567","title":"Effects of exercise testing on natriuretic peptide secretion in patients with atrial fibrillation.","authors":"Wozakowska-Kapłon, Beata; Opolski, Grzegorz","year":2009,"journal":"Kardiologia polska, 67(3), 254-61","doi":null,"pmid":"19378231","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Exercise testing in AF patients produced significant ANP and BNP increases, with post-exercise peptide levels providing additional diagnostic information for assessing cardiac function during AF.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01568","title":"Structure and function of a custom anticancer peptide, CB1a.","authors":"Wu, Jiun-Ming; Jan, Pey-Shynan; Yu, Hui-Chen; Haung, Hsu-Yuang; Fang, Huey-Jen; Chang, Yuan-I; Cheng, Jya-Wei; Chen, Hueih Min","year":2009,"journal":"Peptides, 30(5), 839-48","doi":"10.1016/j.peptides.2009.02.004","pmid":"19428759","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CB1a, a rationally designed anticancer peptide, showed selective tumor cell killing through membrane disruption with characterized 3D structure — demonstrating successful de novo anticancer peptide engineering.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01569","title":"Macrocyclic inhibitors for the serine protease plasmin.","authors":"Xue, Fengtian; Seto, Christopher T","year":2009,"journal":"Journal of enzyme inhibition and medicinal chemistry, 24(3), 779-94","doi":"10.1080/14756360802364401","pmid":"18825554","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Macrocyclic inhibitors targeting the serine protease plasmin showed potent enzyme inhibition, advancing macrocyclic drug design for controlling excessive blood clot dissolution — relevant to bleeding disorders.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01570","title":"Effect of carperitide on plasma adiponectin levels in acute decompensated heart failure patients with diabetes mellitus.","authors":"Yamaji, Masayuki; Tsutamoto, Takayoshi; Tanaka, Toshinari; Kawahara, Chiho; Nishiyama, Keizo; Yamamoto, Takashi; Fujii, Masanori; Horie, Minoru","year":2009,"journal":"Circulation journal : official journal of the Japanese Circulation Society, 73(12), 2264-9","doi":null,"pmid":"19797823","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Carperitide (ANP analog) infusion increased plasma adiponectin in acute decompensated heart failure patients with diabetes, revealing a beneficial metabolic effect of natriuretic peptide therapy.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01571","title":"Arginine vasopressin antinociception in the rat nucleus raphe magnus is involved in the endogenous opiate peptide and serotonin system.","authors":"Yang, Jun; Yuan, Huifeng; Chu, Jiegen; Yang, Yu; Xu, Hongtao; Wang, Gen; Liu, Wen-Yan; Lin, Bao-Cheng","year":2009,"journal":"Peptides, 30(7), 1355-61","doi":"10.1016/j.peptides.2009.03.014","pmid":"19540433","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"AVP antinociception in the nucleus raphe magnus was mediated by both endogenous opioid peptides and serotonin, revealing dual-neurotransmitter signaling for vasopressin's pain control in the brainstem.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01572","title":"Endogenous opiate peptides in the spinal cord are involved in the analgesia of hypothalamic paraventricular nucleus in the rat.","authors":"Yang, Jun; Yang, Yu; Chu, Jiegen; Wang, Gen; Xu, Hongtao; Liu, Wen-Yan; Wang, Cheng-Hai; Lin, Bao-Cheng","year":2009,"journal":"Peptides, 30(4), 740-4","doi":null,"pmid":"19452637","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Analgesia from hypothalamic paraventricular nucleus vasopressin involved endogenous opioid peptide release in the spinal cord, establishing a hypothalamic-spinal vasopressin-opioid pain control axis.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01573","title":"Ghrelin fluctuation, what determines its production?","authors":"Yin, Xuefeng; Li, Yin; Xu, Geyang; An, Wenjiao; Zhang, Weizhen","year":2009,"journal":"Acta biochimica et biophysica Sinica, 41(3), 188-97","doi":null,"pmid":"19280057","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Ghrelin production is regulated by meal timing, macronutrients, hormones (insulin, leptin, GH), neural signals, and disease states — a multi-factorial regulation system that explains ghrelin's complex dynamics.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01574","title":"Self-assembling peptide nanofiber scaffolds, platelet-rich plasma, and mesenchymal stem cells for injectable bone regeneration with tissue engineering.","authors":"Yoshimi, Ryoko; Yamada, Yoichi; Ito, Kenji; Nakamura, Sayaka; Abe, Akihiro; Nagasaka, Tetsuro; Okabe, Kazuto; Kohgo, Tomoyuki; Baba, Shunsuke; Ueda, Minoru","year":2009,"journal":"The Journal of craniofacial surgery, 20(5), 1523-30","doi":"10.1097/SCS.0b013e3181b09b7e","pmid":"19816290","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Combining self-assembling peptide nanofiber scaffolds with mesenchymal stem cells and platelet-rich plasma created an injectable bone regeneration system — a practical bone repair technology.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01575","title":"A prolonged nitric oxide-dependent, opioid-mediated antinociceptive effect of hyperbaric oxygen in mice.","authors":"Zelinski, Lisa M; Ohgami, Yusuke; Chung, Eunhee; Shirachi, Donald Y; Quock, Raymond M","year":2009,"journal":"The journal of pain, 10(2), 167-72","doi":"10.1016/j.jpain.2008.08.003","pmid":"18976963","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Hyperbaric oxygen produced prolonged pain relief through a NO-dependent, opioid-mediated mechanism — both nitric oxide signaling and endogenous opioid peptide release were required for the analgesic effect.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01576","title":"Inhibition of endoplasm reticulum stress by ghrelin protects against ischemia/reperfusion injury in rat heart.","authors":"Zhang, Gai-Gai; Teng, Xu; Liu, Yue; Cai, Yan; Zhou, Ye-Bo; Duan, Xiao-Hui; Song, Jun-Qiu; Shi, Yi; Tang, Chao-Shu; Yin, Xin-Hua; Qi, Yong-Fen","year":2009,"journal":"Peptides, 30(6), 1109-16","doi":"10.1016/j.peptides.2009.03.024","pmid":"19406177","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01577","title":"Self-assembled peptide-based hydrogels as scaffolds for anchorage-dependent cells.","authors":"Zhou, Mi; Smith, Andrew M; Das, Apurba K; Hodson, Nigel W; Collins, Richard F; Ulijn, Rein V; Gough, Julie E","year":2009,"journal":"Biomaterials, 30(13), 2523-30","doi":"10.1016/j.biomaterials.2009.01.010","pmid":"19201459","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Self-assembled peptide hydrogels serve as versatile scaffolds for anchorage-dependent cell culture, supporting various cell types for tissue engineering — from concept to practical application review.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01578","title":"Vasoactive intestinal peptide loss leads to impaired CNS parenchymal T-cell infiltration and resistance to experimental autoimmune encephalomyelitis.","authors":"Abad, Catalina; Tan, Yossan-Var; Lopez, Robert; Nobuta, Hiroko; Dong, Hongmei; Phan, Phu; Feng, Ji-Ming; Campagnoni, Anthony T; Waschek, James A","year":2010,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 107(45), 19555-60","doi":"10.1073/pnas.1007622107","pmid":"20978211","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"VIP deficiency impaired T-cell infiltration into brain tissue and paradoxically increased resistance to EAE (MS model), revealing VIP's complex role in both enabling and modulating brain autoimmune inflammation.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01579","title":"Diminished endometrial expression of ghrelin and ghrelin receptor contributes to infertility.","authors":"Aghajanova, Lusine; Rumman, Amani; Altmäe, Signe; Wånggren, Kjell; Stavreus-Evers, Anneli","year":2010,"journal":"Reproductive sciences (Thousand Oaks, Calif.), 17(9), 823-32","doi":"10.1177/1933719110371683","pmid":"20616368","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Diminished endometrial ghrelin and GHS-R expression was associated with infertility in women, suggesting the uterine ghrelin system is necessary for successful embryo implantation and early pregnancy.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01580","title":"Promoting social behavior with oxytocin in high-functioning autism spectrum disorders.","authors":"Andari, Elissar; Duhamel, Jean-René; Zalla, Tiziana; Herbrecht, Evelyn; Leboyer, Marion; Sirigu, Angela","year":2010,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 107(9), 4389-94","doi":"10.1073/pnas.0910249107","pmid":"20160081","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01581","title":"Vasoactive intestinal peptide induces cell cycle arrest and regulatory functions in human T cells at multiple levels.","authors":"Anderson, Per; Gonzalez-Rey, Elena","year":2010,"journal":"Molecular and cellular biology, 30(10), 2537-51","doi":"10.1128/MCB.01282-09","pmid":"20231362","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"VIP induced cell cycle arrest in human T-cells while simultaneously activating regulatory (suppressive) functions, providing the cellular mechanism for VIP's immunosuppressive therapeutic effects.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01582","title":"Study of the interaction of lactoferricin B with phospholipid monolayers and bilayers.","authors":"Arseneault, Marjolaine; Bédard, Sarah; Boulet-Audet, Maxime; Pézolet, Michel","year":2010,"journal":"Langmuir : the ACS journal of surfaces and colloids, 26(5), 3468-78","doi":"10.1021/la903014w","pmid":"20112931","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Detailed biophysical study of lactoferricin B interaction with phospholipid monolayers and bilayers revealed specific membrane insertion mechanisms that explain its antimicrobial selectivity.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01583","title":"Do the actions of glucagon-like peptide-1 on gastric emptying, appetite, and food intake involve release of amylin in humans?","authors":"Asmar, Meena; Bache, Michael; Knop, Filip K; Madsbad, Sten; Holst, Jens J","year":2010,"journal":"The Journal of clinical endocrinology and metabolism, 95(5), 2367-75","doi":"10.1210/jc.2009-2133","pmid":"20194711","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1's effects on gastric emptying, appetite, and food intake were investigated for amylin co-release involvement in humans, finding that GLP-1's actions are largely independent of amylin — separate satiety pathways.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01584","title":"Effects of a growth hormone-releasing hormone antagonist on telomerase activity, oxidative stress, longevity, and aging in mice.","authors":"Banks, William A; Morley, John E; Farr, Susan A; Price, Tulin O; Ercal, Nuran; Vidaurre, Irving; Schally, Andrew V","year":2010,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 107(51), 22272-7","doi":"10.1073/pnas.1016369107","pmid":"21135231","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A GHRH antagonist modulated telomerase activity, oxidative stress markers, and longevity indicators in mice, revealing the GHRH-GH axis's direct connection to fundamental aging mechanisms.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01585","title":"The human cathelicidin LL-37 preferentially promotes apoptosis of infected airway epithelium.","authors":"Barlow, Peter G; Beaumont, Paula E; Cosseau, Celine; Mackellar, Annie; Wilkinson, Thomas S; Hancock, Robert E W; Haslett, Chris; Govan, John R W; Simpson, A John; Davidson, Donald J","year":2010,"journal":"American journal of respiratory cell and molecular biology, 43(6), 692-702","doi":"10.1165/rcmb.2009-0250OC","pmid":"20097832","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01586","title":"Therapeutic vaccination against a murine lymphoma by intratumoral injection of a cationic anticancer peptide.","authors":"Berge, Gerd; Eliassen, Liv Tone; Camilio, Ketil Andre; Bartnes, Kristian; Sveinbjørnsson, Baldur; Rekdal, Oystein","year":2010,"journal":"Cancer immunology, immunotherapy : CII, 59(8), 1285-94","doi":"10.1007/s00262-010-0857-6","pmid":"20422410","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Intratumoral injection of a cationic anticancer peptide not only killed local tumor cells but generated systemic anti-tumor immunity (therapeutic vaccination effect) that protected against distant tumor challenge.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01587","title":"Glucagon-like Peptide-1 receptor agonists activate rodent thyroid C-cells causing calcitonin release and C-cell proliferation.","authors":"Bjerre Knudsen, Lotte; Madsen, Lars Wichmann; Andersen, Søren; Almholt, Kasper; de Boer, Anne S; Drucker, Daniel J; Gotfredsen, Carsten; Egerod, Frederikke Lihme; Hegelund, Anne Charlotte; Jacobsen, Helene; Jacobsen, Søren Dyring; Moses, Alan C; Mølck, Anne-Marie; Nielsen, Henriette S; Nowak, Jette; Solberg, Helene; Thi, Tu D L; Zdravkovic, Milan; Moerch, Ulrik","year":2010,"journal":"Endocrinology, 151(4), 1473-86","doi":"10.1210/en.2009-1272","pmid":"20203154","tags":[],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"GLP-1 receptor agonists including liraglutide caused thyroid C-cell hyperplasia and calcitonin release in rodents through a GLP-1 receptor-mediated mechanism. However, this effect appears species-specific: human and monkey thyroid C-cells had low GLP-1 receptor expression, GLP-1 agonists did not activate calcitonin release in primate cells, and 20 months of liraglutide treatment at >60x human exposure did not cause C-cell hyperplasia in monkeys. In human patients treated with liraglutide for 2 years, calcitonin levels remained at the lower end of normal with no meaningful increase above clinically relevant thresholds.","whyItMatters":"This is the key study that explained why GLP-1 drugs carry a thyroid cancer warning on their labels — rodent studies showed thyroid tumors — while providing the first strong evidence that this risk may not translate to humans. It delineated a species-specific difference in GLP-1 receptor biology that has been central to the safety debate around every GLP-1 RA since.","specificNumbers":">60x human exposure in monkeys for 20 months · No C-cell hyperplasia in primates · Human calcitonin remained in lower normal range · 2-year human exposure data · Cutoff: 20 pg/ml calcitonin","methodology":"Multi-species study: GLP-1 receptor localization via immunohistochemistry in rodent, monkey, and human thyroid tissue. Calcitonin release and gene expression measured in rodent C-cells. Adenylate cyclase activation tested in primate cells. 20-month liraglutide treatment in cynomolgus monkeys at >60x human exposure. 2-year calcitonin monitoring data from human clinical trials.","limitations":"The human data comes from clinical trial calcitonin monitoring, not direct thyroid tissue examination. Long-term consequences of sustained GLP-1 receptor activation in human thyroid remain unknown. The 2-year human follow-up may not be sufficient to detect very slow-growing thyroid cancers. Monkey study used one GLP-1 RA (liraglutide) and may not generalize to all agents."},{"rthcId":"RPEP-01588","title":"Solid-phase synthesis of a pentavalent GalNAc-containing glycopeptide (Tn antigen) representing the nephropathy-associated IgA hinge region.","authors":"Bolscher, Jan G M; Brevoord, Judith; Nazmi, Kamran; Ju, Tongzhong; Veerman, Enno C I; van Wijk, Joanna A E; Cummings, Richard D; van Die, Irma","year":2010,"journal":"Carbohydrate research, 345(14), 1998-2003","doi":"10.1016/j.carres.2010.07.022","pmid":"20719305","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Solid-phase synthesis of a pentavalent GalNAc glycopeptide representing the IgA nephropathy-associated Tn antigen enables research into this kidney disease's immune mechanism and potential vaccine approaches.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01589","title":"Antimicrobial and cell-penetrating peptides: structure, assembly and mechanisms of membrane lysis via atomistic and coarse-grained molecular dynamics simulations.","authors":"Bond, Peter J; Khalid, Syma","year":2010,"journal":"Protein and peptide letters, 17(11), 1313-27","doi":null,"pmid":"20673230","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01590","title":"Diet-induced obesity causes ghrelin resistance in arcuate NPY/AgRP neurons.","authors":"Briggs, Dana I; Enriori, Pablo J; Lemus, Moyra B; Cowley, Michael A; Andrews, Zane B","year":2010,"journal":"Endocrinology, 151(10), 4745-55","doi":"10.1210/en.2010-0556","pmid":"20826561","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01591","title":"Rational redesign of porcine pepsinogen containing an antimicrobial peptide.","authors":"Bryksa, Brian C; Horimoto, Yasumi; Yada, Rickey Y","year":2010,"journal":"Protein engineering, design & selection : PEDS, 23(9), 711-9","doi":"10.1093/protein/gzq039","pmid":"20601363","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Porcine pepsinogen was rationally redesigned to incorporate an antimicrobial peptide sequence, creating a fusion protein that retains both digestive enzyme activity and antibacterial properties — a dual-function gastric protector.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01592","title":"Terminal signal: anti-inflammatory effects of α-melanocyte-stimulating hormone related peptides beyond the pharmacophore.","authors":"Brzoska, Thomas; Böhm, Markus; Lügering, Andreas; Loser, Karin; Luger, Thomas A","year":2010,"journal":"Advances in experimental medicine and biology, 681, 107-16","doi":"10.1007/978-1-4419-6354-3_8","pmid":"21222263","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Alpha-MSH C-terminal peptides beyond the known KPV pharmacophore showed anti-inflammatory activity, revealing the C-terminal signal extends further than the classic tripeptide — expanded anti-inflammatory peptide toolkit.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01593","title":"Cathelicidin LL-37: a multitask antimicrobial peptide.","authors":"Bucki, Robert; Leszczyńska, Katarzyna; Namiot, Andrzej; Sokołowski, Wojciech","year":2010,"journal":"Archivum immunologiae et therapiae experimentalis, 58(1), 15-25","doi":"10.1007/s00005-009-0057-2","pmid":"20049649","tags":["antimicrobial-peptides","cathelicidins"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"LL-37 — the only human cathelicidin antimicrobial peptide — does far more than kill bacteria. This review catalogs its many roles: it kills a broad range of microorganisms, neutralizes bacterial toxins (LPS) to prevent septic shock, attracts immune cells to infection sites, prevents neutrophil death, stimulates new blood vessel growth, promotes tissue repair, and triggers cytokine release. Its production is regulated by vitamin D (which explains the sun exposure-immunity connection), bacterial products, and oxygen levels. However, at inflamed sites, DNA and proteins from dead cells can neutralize LL-37, limiting its effectiveness.","whyItMatters":"LL-37 is the only cathelicidin peptide humans produce, making it uniquely important in our innate immune defense. Understanding its multiple functions — from direct microbial killing to wound healing to immune signaling — is essential for developing it as a therapeutic agent. The vitamin D connection also has public health implications, as vitamin D deficiency may impair LL-37 production and compromise immune defense.","specificNumbers":"","methodology":"This is a comprehensive review paper synthesizing published research on LL-37's antimicrobial activity, immunomodulatory functions, gene regulation, and potential therapeutic applications.","limitations":"As a review paper, no new experimental data are presented. The therapeutic applications of LL-37 discussed were largely theoretical at the time of publication. The review may not capture more recent discoveries about LL-37's roles in autoimmune conditions and cancer."},{"rthcId":"RPEP-01594","title":"DURATION-1: exenatide once weekly produces sustained glycemic control and weight loss over 52 weeks.","authors":"Buse, John B; Drucker, Daniel J; Taylor, Kristin L; Kim, Terri; Walsh, Brandon; Hu, Hao; Wilhelm, Ken; Trautmann, Michael; Shen, Larry Z; Porter, Lisa E","year":2010,"journal":"Diabetes care, 33(6), 1255-61","doi":"10.2337/dc09-1914","pmid":"20215461","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01595","title":"Pentadecapeptide BPC 157 (PL 14736) improves ligament healing in the rat.","authors":"Cerovecki, Tomislav; Bojanic, Ivan; Brcic, Luka; Radic, Bozo; Vukoja, Ivan; Seiwerth, Sven; Sikiric, Predrag","year":2010,"journal":"Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 28(9), 1155-61","doi":"10.1002/jor.21107","pmid":"20225319","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BPC-157 (PL 14736) accelerated medial collateral ligament healing in rats with improved biomechanical and histological outcomes, extending its musculoskeletal healing from tendons and muscles to ligaments.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01596","title":"Optimization of the native glucagon sequence for medicinal purposes.","authors":"Chabenne, Joseph R; DiMarchi, Maria A; Gelfanov, Vasily M; DiMarchi, Richard D","year":2010,"journal":"Journal of diabetes science and technology, 4(6), 1322-31","doi":null,"pmid":"21129326","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Systematic optimization of the native glucagon sequence produced analogs with improved stability, selectivity, and pharmacokinetics for potential dual GLP-1/glucagon receptor agonist obesity and diabetes drugs.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01597","title":"Bioactivity and pharmacokinetics of two human serum albumin-thymosin alpha1-fusion proteins, rHSA-Talpha1 and rHSA-L-Talpha1, expressed in recombinant Pichia pastoris.","authors":"Chen, Jian-Hua; Zhang, Xin-Guo; Jiang, Yu-Tao; Yan, Lu-Ying; Tang, Li; Yin, Yi-Wei; Cheng, Dai-Shuang; Chen, Jing; Wang, Min","year":2010,"journal":"Cancer immunology, immunotherapy : CII, 59(9), 1335-45","doi":"10.1007/s00262-010-0862-9","pmid":"20473755","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Thymosin alpha-1 fused to human serum albumin (HSA) achieved dramatically extended half-life while retaining immunostimulatory activity — enabling less frequent dosing for sustained immune therapy.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01598","title":"A new \"era\" for cyclotide sequencing.","authors":"Colgrave, Michelle L; Poth, Aaron G; Kaas, Quentin; Craik, David J","year":2010,"journal":"Biopolymers, 94(5), 592-601","doi":"10.1002/bip.21400","pmid":"20564007","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Advanced mass spectrometry techniques enabled more efficient cyclotide discovery, sequencing, and characterization — expanding the known cyclotide family and accelerating drug scaffold identification.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01599","title":"Structural and pharmacological characteristics of chimeric peptides derived from peptide E and beta-endorphin reveal the crucial role of the C-terminal YGGFL and YKKGE motifs in their analgesic properties.","authors":"Condamine, Eric; Courchay, Karine; Rego, Jean-Claude Do; Leprince, Jérôme; Mayer, Catherine; Davoust, Daniel; Costentin, Jean; Vaudry, Hubert","year":2010,"journal":"Peptides, 31(5), 962-72","doi":"10.1016/j.peptides.2010.01.012","pmid":"20138196","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Chimeric peptides combining regions of peptide E and beta-endorphin revealed distinct structural requirements for mu vs delta opioid receptor activation, guiding design of receptor-selective opioid analgesics.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01600","title":"Cyclotides: macrocyclic peptides with applications in drug design and agriculture.","authors":"Craik, David J; Mylne, Joshua S; Daly, Norelle L","year":2010,"journal":"Cellular and molecular life sciences : CMLS, 67(1), 9-16","doi":"10.1007/s00018-009-0159-3","pmid":"19795188","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Updated cyclotide review covering drug design applications (stable scaffolds for oral drugs) and agricultural uses (insecticidal, antimicrobial) — nature's circular peptides finding practical applications.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01601","title":"The role of nutraceutical proteins and peptides in apoptosis, angiogenesis, and metastasis of cancer cells.","authors":"de Mejia, Elvira Gonzalez; Dia, Vermont P","year":2010,"journal":"Cancer metastasis reviews, 29(3), 511-28","doi":"10.1007/s10555-010-9241-4","pmid":"20714786","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Nutraceutical proteins and peptides (lactoferricin, soy peptides, casein-derived) showed anticancer activities including apoptosis induction, angiogenesis inhibition, and metastasis suppression — food-derived cancer fighters.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01602","title":"Effects of ghrelin, growth hormone-releasing peptide-6, and growth hormone-releasing hormone on growth hormone, adrenocorticotropic hormone, and cortisol release in type 1 diabetes mellitus.","authors":"de Sá, Larissa Bianca Paiva Cunha; Nascif, Sergio Oliva; Correa-Silva, Silvia Regina; Molica, Patricia; Vieira, José Gilberto Henriques; Dib, Sergio Atala; Lengyel, Ana-Maria Judith","year":2010,"journal":"Metabolism: clinical and experimental, 59(10), 1536-42","doi":"10.1016/j.metabol.2010.01.021","pmid":"20189610","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Direct comparison of ghrelin, GHRP-6, and GHRH effects on GH, ACTH, cortisol, and prolactin in humans revealed distinct hormonal profiles — guiding clinical selection of the optimal GH stimulation test.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01603","title":"Focus on the short- and long-term effects of ghrelin on energy homeostasis.","authors":"De Vriese, Carine; Perret, Jason; Delporte, Christine","year":2010,"journal":"Nutrition (Burbank, Los Angeles County, Calif.), 26(6), 579-84","doi":"10.1016/j.nut.2009.09.013","pmid":"20080032","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Ghrelin's energy homeostasis effects span short-term meal-to-meal appetite stimulation and long-term body weight/composition regulation, with different mechanisms and therapeutic implications for each timescale.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01604","title":"Gastrointestinal targets of appetite regulation in humans.","authors":"Delzenne, N; Blundell, J; Brouns, F; Cunningham, K; De Graaf, K; Erkner, A; Lluch, A; Mars, M; Peters, H P F; Westerterp-Plantenga, M","year":2010,"journal":"Obesity reviews : an official journal of the International Association for the Study of Obesity, 11(3), 234-50","doi":"10.1111/j.1467-789X.2009.00707.x","pmid":"20433660","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Gastrointestinal appetite targets span mechanoreceptors (stomach distension), gut peptides (GLP-1, PYY, CCK, ghrelin), nutrient sensors, and microbiome-derived signals — the complete GI appetite regulation toolkit.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01605","title":"Acceleration of wound healing by growth hormone-releasing hormone and its agonists.","authors":"Dioufa, Nikolina; Schally, Andrew V; Chatzistamou, Ioulia; Moustou, Evi; Block, Norman L; Owens, Gary K; Papavassiliou, Athanasios G; Kiaris, Hippokratis","year":2010,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 107(43), 18611-5","doi":"10.1073/pnas.1013942107","pmid":"20937882","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GHRH and its synthetic agonists accelerated wound healing through direct cellular effects (fibroblast proliferation, collagen synthesis) and GH/IGF-1 mediation — a new wound healing application for the GH-axis.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01606","title":"Ghrelin receptor: high constitutive activity and methods for developing inverse agonists.","authors":"Els, Sylvia; Beck-Sickinger, Annette G; Chollet, Constance","year":2010,"journal":"Methods in enzymology, 485, 103-21","doi":"10.1016/B978-0-12-381296-4.00006-3","pmid":"21050913","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The ghrelin receptor's constitutive activity (always partially active) can be blocked by inverse agonists, which reduce the receptor's baseline signaling — a more effective obesity strategy than simple antagonism.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01607","title":"Production of thymosin alpha1 via non-enzymatic acetylation of the recombinant precursor.","authors":"Esipov, Roman S; Stepanenko, Vasily N; Beyrakhova, Ksenia A; Muravjeva, Tatjana I; Miroshnikov, Anatoly I","year":2010,"journal":"Biotechnology and applied biochemistry, 56(1), 17-25","doi":"10.1042/BA20100027","pmid":"20408810","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Thymosin alpha-1 was produced from its bacterial recombinant precursor via non-enzymatic acetylation, simplifying manufacturing by eliminating the need for enzymatic N-terminal acetylation.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01608","title":"Effects of tesamorelin, a growth hormone-releasing factor, in HIV-infected patients with abdominal fat accumulation: a randomized placebo-controlled trial with a safety extension.","authors":"Falutz, Julian; Potvin, Diane; Mamputu, Jean-Claude; Assaad, Hani; Zoltowska, Monika; Michaud, Sophie-Elise; Berger, Daniel; Somero, Michael; Moyle, Graeme; Brown, Stephen; Martorell, Claudia; Turner, Ralph; Grinspoon, Steven","year":2010,"journal":"Journal of acquired immune deficiency syndromes (1999), 53(3), 311-22","doi":"10.1097/QAI.0b013e3181cbdaff","pmid":"20101189","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01609","title":"Expression and purification of an antimicrobial peptide, bovine lactoferricin derivative LfcinB-W10 in Escherichia coli.","authors":"Feng, Xingjun; Liu, Chunlong; Guo, Jiayin; Bi, Chongpeng; Cheng, Baojing; Li, Zhongyu; Shan, Anshan; Li, Zhongqiu","year":2010,"journal":"Current microbiology, 60(3), 179-84","doi":"10.1007/s00284-009-9522-8","pmid":"19847484","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"An enhanced bovine lactoferricin variant (LfcinB-W10) was expressed and purified from E. coli with retained antimicrobial activity — manufacturing the optimized peptide for practical antimicrobial use.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01610","title":"Lactoferricin B-derived peptides with inhibitory effects on ECE-dependent vasoconstriction.","authors":"Fernández-Musoles, Ricardo; López-Díez, José Javier; Torregrosa, Germán; Vallés, Salvador; Alborch, Enrique; Manzanares, Paloma; Salom, Juan B","year":2010,"journal":"Peptides, 31(10), 1926-33","doi":"10.1016/j.peptides.2010.06.024","pmid":"20600419","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Lactoferricin B-derived peptides inhibited endothelin-converting enzyme (ECE)-dependent vasoconstriction, adding blood pressure regulation through endothelin pathway to antimicrobial and ACE-inhibitory activities — triple cardiovascular function.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01611","title":"Trypanosoma cruzi: synergistic cytotoxicity of multiple amphipathic anti-microbial peptides to T. cruzi and potential bacterial hosts.","authors":"Fieck, Annabeth; Hurwitz, Ivy; Kang, Angray S; Durvasula, Ravi","year":2010,"journal":"Experimental parasitology, 125(4), 342-7","doi":"10.1016/j.exppara.2010.02.016","pmid":"20206169","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Multiple antimicrobial peptides showed synergistic cytotoxicity against Trypanosoma cruzi (Chagas disease parasite) and host bacteria, identifying peptide combination therapy for this neglected tropical disease.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01612","title":"Bactericidal effect of bovine lactoferrin, LFcin, LFampin and LFchimera on antibiotic-resistant Staphylococcus aureus and Escherichia coli.","authors":"Flores-Villaseñor, Héctor; Canizalez-Román, Adrian; Reyes-Lopez, Magda; Nazmi, Kamram; de la Garza, Mireya; Zazueta-Beltrán, Jorge; León-Sicairos, Nidia; Bolscher, Jan G M","year":2010,"journal":"Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine, 23(3), 569-78","doi":"10.1007/s10534-010-9306-4","pmid":"20195887","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Bovine lactoferrin, lactoferricin, lactoferrampin, and LFchimera all killed antibiotic-resistant S. aureus and Streptococcus species, demonstrating the milk-derived peptide family's activity against dangerous resistant pathogens.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01613","title":"Unique biological function of cathepsin L in secretory vesicles for biosynthesis of neuropeptides.","authors":"Funkelstein, Lydiane; Beinfeld, Margery; Minokadeh, Ardalan; Zadina, James; Hook, Vivian","year":2010,"journal":"Neuropeptides, 44(6), 457-66","doi":"10.1016/j.npep.2010.08.003","pmid":"21047684","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Cathepsin L was identified as uniquely essential for processing neuropeptide precursors in secretory vesicles, revealing how the body manufactures its own bioactive peptides from larger precursor proteins.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01614","title":"Identification and characterization of the parasitic wasp Nasonia defensins: positive selection targeting the functional region?","authors":"Gao, Bin; Zhu, Shunyi","year":2010,"journal":"Developmental and comparative immunology, 34(6), 659-68","doi":"10.1016/j.dci.2010.01.012","pmid":"20097222","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01615","title":"Release of satiety hormones in response to specific dietary proteins is different between human and murine small intestinal mucosa.","authors":"Geraedts, Maartje C P; Troost, Freddy J; Tinnemans, Rik; Söderholm, Johan D; Brummer, Robert-Jan; Saris, Wim H M","year":2010,"journal":"Annals of nutrition & metabolism, 56(4), 308-13","doi":"10.1159/000312664","pmid":"20530962","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Specific dietary proteins released different patterns of satiety hormones (GLP-1, CCK, PYY) from human versus mouse intestinal cells, highlighting species differences that affect translating appetite research from animals to humans.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01616","title":"Peptide therapy with pentadecapeptide BPC 157 in traumatic nerve injury.","authors":"Gjurasin, Miroslav; Miklic, Pavle; Zupancic, Bozidar; Perovic, Darko; Zarkovic, Kamelija; Brcic, Luka; Kolenc, Danijela; Radic, Bozo; Seiwerth, Sven; Sikiric, Predrag","year":2010,"journal":"Regulatory peptides, 160(1-3), 33-41","doi":"10.1016/j.regpep.2009.11.005","pmid":"19903499","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BPC-157 improved healing of traumatic peripheral nerve injury in rats, enhancing nerve regeneration and functional recovery — adding nerve repair to its expanding tissue healing capabilities.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01617","title":"Peptides targeting Toll-like receptor signalling pathways for novel immune therapeutics.","authors":"Gomariz, R P; Gutiérrez-Cañas, I; Arranz, A; Carrión, M; Juarranz, Y; Leceta, J; Martínez, C","year":2010,"journal":"Current pharmaceutical design, 16(9), 1063-80","doi":null,"pmid":"20030612","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Peptides targeting Toll-like receptor (TLR) signaling pathways offer new immune therapeutic opportunities — both TLR agonist peptides for immune activation and antagonist peptides for anti-inflammatory applications.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01618","title":"Neuropeptides as therapeutic approach to autoimmune diseases.","authors":"Gonzalez-Rey, Elena; Delgado-Maroto, Virginia; Souza Moreira, Luciana; Delgado, Mario","year":2010,"journal":"Current pharmaceutical design, 16(28), 3158-72","doi":null,"pmid":"20687881","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Neuropeptides (VIP, alpha-MSH/KPV, CGRP, cortistatin) as therapeutic approaches for autoimmune diseases including RA, MS, and IBD — comprehensive 2010 review of the anti-autoimmune neuropeptide therapeutic landscape.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01619","title":"Naturally occurring human urinary peptides for use in diagnosis of chronic kidney disease.","authors":"Good, David M; Zürbig, Petra; Argilés, Angel; Bauer, Hartwig W; Behrens, Georg; Coon, Joshua J; Dakna, Mohammed; Decramer, Stéphane; Delles, Christian; Dominiczak, Anna F; Ehrich, Jochen H H; Eitner, Frank; Fliser, Danilo; Frommberger, Moritz; Ganser, Arnold; Girolami, Mark A; Golovko, Igor; Gwinner, Wilfried; Haubitz, Marion; Herget-Rosenthal, Stefan; Jankowski, Joachim; Jahn, Holger; Jerums, George; Julian, Bruce A; Kellmann, Markus; Kliem, Volker; Kolch, Walter; Krolewski, Andrzej S; Luppi, Mario; Massy, Ziad; Melter, Michael; Neusüss, Christian; Novak, Jan; Peter, Karlheinz; Rossing, Kasper; Rupprecht, Harald; Schanstra, Joost P; Schiffer, Eric; Stolzenburg, Jens-Uwe; Tarnow, Lise; Theodorescu, Dan; Thongboonkerd, Visith; Vanholder, Raymond; Weissinger, Eva M; Mischak, Harald; Schmitt-Kopplin, Philippe","year":2010,"journal":"Molecular & cellular proteomics : MCP, 9(11), 2424-37","doi":"10.1074/mcp.M110.001917","pmid":"20616184","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01620","title":"The positive effects of growth hormone-releasing peptide-6 on weight gain and fat mass accrual depend on the insulin/glucose status.","authors":"Granado, Miriam; García-Cáceres, Cristina; Frago, Laura M; Argente, Jesús; Chowen, Julie A","year":2010,"journal":"Endocrinology, 151(5), 2008-18","doi":"10.1210/en.2009-1394","pmid":"20219977","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GHRP-6's fat-gaining effects were dependent on insulin/glucose metabolic status, with insulin resistance modifying the weight gain response — metabolic context determines whether GH peptides promote or prevent weight gain.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01621","title":"Helix formation in preorganized beta/gamma-peptide foldamers: hydrogen-bond analogy to the alpha-helix without alpha-amino acid residues.","authors":"Guo, Li; Almeida, Aaron M; Zhang, Weicheng; Reidenbach, Andrew G; Choi, Soo Hyuk; Guzei, Ilia A; Gellman, Samuel H","year":2010,"journal":"Journal of the American Chemical Society, 132(23), 7868-9","doi":"10.1021/ja103233a","pmid":"20491510","tags":["peptide-chemistry","peptide-engineering","structural-biology"],"studyType":"in-vitro","evidenceStrength":"strong","keyFinding":"The researchers provided the first high-resolution structural data for the beta/gamma-peptide 13-helix — a secondary structure formed by oligomers with a 1:1 alternation of beta- and gamma-amino acid residues. The structure was confirmed by both X-ray crystallography and 2D NMR spectroscopy.\n\nThe 13-helix features i,i+3 C=O...H-N hydrogen bonds, creating a folding pattern analogous to the alpha-helix found in natural proteins but built entirely without natural alpha-amino acids. The key to achieving this fold was using preorganized (conformationally constrained) beta- and gamma-residues, which strongly promote 13-helical folding. Previous studies with conformationally flexible residues had resulted in different helical structures.","whyItMatters":"One of the biggest challenges in peptide drug development is that natural peptides are rapidly chewed up by enzymes in the body. Foldamers — artificial peptides built from non-natural building blocks — resist these enzymes because the body's proteases don't recognize their unusual backbone chemistry. But for foldamers to be useful as drugs, they need to fold into defined shapes that can interact with biological targets. This study proves that beta/gamma-peptides can form stable, well-defined helices, making them promising scaffolds for designing enzyme-resistant peptide therapeutics.","specificNumbers":"13-helix structure · 1:1 beta/gamma amino acid alternation · i,i+3 hydrogen bonding pattern · X-ray crystallography + 2D NMR confirmation","methodology":"This was a synthetic chemistry and structural biology study. The researchers designed and synthesized beta/gamma-peptide sequences using preorganized (conformationally constrained) amino acid residues with alternating beta and gamma building blocks. They characterized the three-dimensional structure using two complementary high-resolution methods: X-ray crystallography (to determine the solid-state structure) and 2D NMR spectroscopy (to confirm the structure exists in solution).","limitations":"This is a pure structural chemistry study with no biological activity data — the foldamers were not tested against any biological target. Only short oligomers were characterized, and it's unclear how longer sequences would behave. The preorganized residues required for stable folding add synthetic complexity that could limit practical applications. No in vivo studies were conducted."},{"rthcId":"RPEP-01622","title":"Pharmacological management of appetite expression in obesity.","authors":"Halford, Jason C G; Boyland, Emma J; Blundell, John E; Kirkham, Tim C; Harrold, Joanne A","year":2010,"journal":"Nature reviews. Endocrinology, 6(5), 255-69","doi":"10.1038/nrendo.2010.19","pmid":"20234354","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Updated review of appetite pharmacology for obesity: GLP-1 agonists (most promising), cannabinoid CB1 antagonists (withdrawn for psychiatric side effects), and combination peptide approaches — the 2010 drug development landscape.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01623","title":"Incretin mimetics: a novel therapeutic option for patients with type 2 diabetes - a review.","authors":"Hansen, Katrine B; Vilsbøll, Tina; Knop, Filip K","year":2010,"journal":"Diabetes, metabolic syndrome and obesity : targets and therapy, 3, 155-63","doi":null,"pmid":"21437085","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Comprehensive review of incretin-based diabetes therapy covering GLP-1 receptor agonists (exenatide, liraglutide) and DPP-4 inhibitors — mechanism, efficacy, safety, and clinical positioning in T2DM management.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01624","title":"Human cathelicidin peptide LL37 inhibits both attachment capability and biofilm formation of Staphylococcus epidermidis.","authors":"Hell, E; Giske, C G; Nelson, A; Römling, U; Marchini, G","year":2010,"journal":"Letters in applied microbiology, 50(2), 211-5","doi":"10.1111/j.1472-765X.2009.02778.x","pmid":"20002576","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01625","title":"The chromogranin A-derived peptides vasostatin-I and catestatin as regulatory peptides for cardiovascular functions.","authors":"Helle, Karen B","year":2010,"journal":"Cardiovascular research, 85(1), 9-16","doi":"10.1093/cvr/cvp266","pmid":"19640932","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01626","title":"Identification of CJC-1295, a growth-hormone-releasing peptide, in an unknown pharmaceutical preparation.","authors":"Henninge, John; Pepaj, Milaim; Hullstein, Ingunn; Hemmersbach, Peter","year":2010,"journal":"Drug testing and analysis, 2(11-12), 647-50","doi":"10.1002/dta.233","pmid":"21204297","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CJC-1295 (long-acting GHRH analog) was identified in an unknown pharmaceutical preparation through analytical chemistry, highlighting its availability in the unregulated peptide market and anti-doping implications.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01627","title":"Improved survival with ipilimumab in patients with metastatic melanoma.","authors":"Hodi, F Stephen; O'Day, Steven J; McDermott, David F; Weber, Robert W; Sosman, Jeffrey A; Haanen, John B; Gonzalez, Rene; Robert, Caroline; Schadendorf, Dirk; Hassel, Jessica C; Akerley, Wallace; van den Eertwegh, Alfons J M; Lutzky, Jose; Lorigan, Paul; Vaubel, Julia M; Linette, Gerald P; Hogg, David; Ottensmeier, Christian H; Lebbé, Celeste; Peschel, Christian; Quirt, Ian; Clark, Joseph I; Wolchok, Jedd D; Weber, Jeffrey S; Tian, Jason; Yellin, Michael J; Nichol, Geoffrey M; Hoos, Axel; Urba, Walter J","year":2010,"journal":"The New England journal of medicine, 363(8), 711-23","doi":"10.1056/NEJMoa1003466","pmid":"20525992","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01628","title":"Egg-derived peptide IRW inhibits TNF-α-induced inflammatory response and oxidative stress in endothelial cells.","authors":"Huang, Wuyang; Chakrabarti, Subhadeep; Majumder, Kaustav; Jiang, Yanyan; Davidge, Sandra T; Wu, Jianping","year":2010,"journal":"Journal of agricultural and food chemistry, 58(20), 10840-6","doi":"10.1021/jf102120c","pmid":"20886881","tags":["food-derived-peptides","cardiovascular"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"IRW, a three-amino-acid peptide derived from egg protein, blocked TNF-α-induced inflammatory responses in human endothelial cells in a dose-dependent manner. Specifically, IRW reduced the production of three key vascular inflammation markers: ICAM-1, VCAM-1, and MCP-1. It also reduced superoxide ion levels (oxidative stress) both with and without TNF-α stimulation. IRW had previously been identified as an ACE (angiotensin converting enzyme) inhibitor, and this study reveals it has additional anti-inflammatory and antioxidant properties beyond blood pressure lowering.","whyItMatters":"Endothelial dysfunction — where blood vessel lining cells become inflamed and damaged — is the earliest step in atherosclerosis and cardiovascular disease. Finding that a simple food-derived tripeptide can simultaneously inhibit ACE, reduce vascular inflammation, and lower oxidative stress suggests egg peptides could have multi-targeted cardiovascular benefits as functional food ingredients.","specificNumbers":"IRW tripeptide · Concentration-dependent inhibition · Reduced ICAM-1, VCAM-1, MCP-1 · Reduced superoxide ions · ACE inhibitory activity · Egg protein-derived","methodology":"In vitro cell culture study using human umbilical vein endothelial cells (HUVECs). Cells were pretreated with IRW peptide at various concentrations, then stimulated with TNF-α to induce inflammation. Protein levels of ICAM-1, VCAM-1, and MCP-1 were measured. Superoxide ion levels were quantified as a measure of oxidative stress.","limitations":"Entirely in vitro — cell culture results may not translate to effects in living blood vessels or whole organisms. The concentrations used in the lab may not be achievable through dietary egg consumption. Whether IRW survives digestion intact to reach blood vessels in meaningful amounts is not addressed. No animal or human studies were conducted."},{"rthcId":"RPEP-01629","title":"Pre- versus postmenopausal age, estradiol, and peptide-secretagogue type determine pulsatile growth hormone secretion in healthy women: studies using submaximal agonist drive and an estrogen clamp.","authors":"Hudson, Susan B; Schroeder, Darrell R; Bailey, Joy N; Mielke, Kristi L; Erickson, Dana; Miles, John M; Bowers, Cyril Y; Veldhuis, Johannes D","year":2010,"journal":"The Journal of clinical endocrinology and metabolism, 95(1), 353-60","doi":"10.1210/jc.2009-1769","pmid":"19858315","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Pre- versus postmenopausal status, estradiol levels, and GH secretagogue type each independently determined pulsatile GH secretion patterns in women — all three factors must be considered for optimal GH therapy.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01630","title":"High hepatotoxic dose of paracetamol produces generalized convulsions and brain damage in rats. A counteraction with the stable gastric pentadecapeptide BPC 157 (PL 14736).","authors":"Ilic, S; Drmic, D; Zarkovic, K; Kolenc, D; Coric, M; Brcic, L; Klicek, R; Radic, B; Sever, M; Djuzel, V; Ivica, M; Boban Blagaic, A; Zoricic, Z; Anic, T; Zoricic, I; Djidic, S; Romic, Z; Seiwerth, S; Sikiric, P","year":2010,"journal":"Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 61(2), 241-50","doi":null,"pmid":"20436226","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BPC-157 counteracted high-dose paracetamol-induced brain damage, seizures, and hepatotoxicity in rats — adding acetaminophen overdose protection to its expanding organ protection profile.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01631","title":"Secretagogue type, sex-steroid milieu, and abdominal visceral adiposity individually determine secretagogue-stimulated cortisol secretion.","authors":"Iranmanesh, Ali; Bowers, Cyril Y; Veldhuis, Johannes D","year":2010,"journal":"European journal of endocrinology, 162(6), 1043-9","doi":"10.1530/EJE-10-0149","pmid":"20299490","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Secretagogue type, sex-steroid environment, and visceral adiposity each independently determined GH secretory response to peptide stimulation — triple-factor personalization needed for GH therapy.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01632","title":"Acute cardiovascular effects of apelin in humans: potential role in patients with chronic heart failure.","authors":"Japp, A G; Cruden, N L; Barnes, G; van Gemeren, N; Mathews, J; Adamson, J; Johnston, N R; Denvir, M A; Megson, I L; Flapan, A D; Newby, D E","year":2010,"journal":"Circulation, 121(16), 1818-27","doi":"10.1161/CIRCULATIONAHA.109.911339","pmid":"20385929","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01633","title":"Enzymatic hydrolysis of Alaska pollack (Theragra chalcogramma) skin and antioxidant activity of the resulting hydrolysate.","authors":"Jia, Jianping; Zhou, Yangang; Lu, Jianzhang; Chen, Aiying; Li, Yuezhong; Zheng, Gaoli","year":2010,"journal":"Journal of the science of food and agriculture, 90(4), 635-40","doi":"10.1002/jsfa.3861","pmid":"20355092","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Enzymatic hydrolysis of Alaska pollack skin produced collagen peptides with significant antioxidant activity, turning fish processing waste into valuable bioactive health supplements.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01634","title":"Effect of sialylated O-glycans in pro-brain natriuretic peptide stability.","authors":"Jiang, Jingjing; Pristera, Nicole; Wang, Wei; Zhang, Xiumei; Wu, Qingyu","year":2010,"journal":"Clinical chemistry, 56(6), 959-66","doi":"10.1373/clinchem.2009.140558","pmid":"20348402","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Sialylated O-glycans on pro-BNP affected its stability and processing, with glycosylation influencing which molecular forms circulate — important for clinical BNP/NT-proBNP assay accuracy.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01635","title":"Evaluation of a (64)Cu-labeled cystine-knot peptide based on agouti-related protein for PET of tumors expressing alphavbeta3 integrin.","authors":"Jiang, Lei; Kimura, Richard H; Miao, Zheng; Silverman, Adam P; Ren, Gang; Liu, Hongguang; Li, Peiyong; Gambhir, Sanjiv Sam; Cochran, Jennifer R; Cheng, Zhen","year":2010,"journal":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 51(2), 251-258","doi":"10.2967/jnumed.109.069831","pmid":"20124048","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A cystine-knot peptide based on agouti-related protein was labeled with 64Cu for PET imaging of tumors expressing αvβ3 integrin, demonstrating cyclotide scaffolds as stable cancer diagnostic imaging agents.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01636","title":"Effect of thymosin-α(1) on T-helper 1 cell and T-helper 2 cell cytokine synthesis in patients with hepatitis B virus e antigen-positive chronic hepatitis B.","authors":"Jiang, Y-F; Ma, Z-H; Zhao, P-W; Pan, Y; Liu, Y-Y; Feng, J-Y; Niu, J-Q","year":2010,"journal":"The Journal of international medical research, 38(6), 2053-62","doi":null,"pmid":"21227010","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Thymosin alpha-1 treatment shifted cytokine profiles from Th2-dominant (infection-permissive) to Th1-dominant (virus-fighting) in HBV patients with hepatitis B e-antigen, confirming its immune repolarization mechanism.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01637","title":"Apelin and ACE2 in cardiovascular disease.","authors":"Kalea, Anastasia Z; Batlle, Daniel","year":2010,"journal":"Current opinion in investigational drugs (London, England : 2000), 11(3), 273-82","doi":null,"pmid":"20178040","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Apelin and ACE2 form a cardiovascular protective axis — apelin through vasodilation and cardiac contractility, ACE2 through angiotensin II degradation — together opposing the harmful renin-angiotensin system.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01638","title":"Evaluation of synthetic cell-penetrating peptides, Pro-rich peptide and octaargine derivatives, as adenovirus vector carrier.","authors":"Kida, Shinya; Eto, Yusuke; Yoshioka, Yasuo; Nakagawa, Shinsaku; Kawasaki, Koichi; Maeda, Mitsuko","year":2010,"journal":"Protein and peptide letters, 17(2), 164-7","doi":null,"pmid":"20214640","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Pro-rich and octaarginine cell-penetrating peptides enhanced adenovirus vector cellular uptake, improving gene therapy delivery efficiency — peptides as tools to boost viral gene therapy.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01639","title":"Synthesis of Tc-99m labeled 1,2,3-triazole-4-yl c-met binding peptide as a potential c-met receptor kinase positive tumor imaging agent.","authors":"Kim, Eun-Mi; Joung, Min-Hee; Lee, Chang-Moon; Jeong, Hwan-Jeong; Lim, Seok Tae; Sohn, Myung-Hee; Kim, Dong Wook","year":2010,"journal":"Bioorganic & medicinal chemistry letters, 20(14), 4240-3","doi":"10.1016/j.bmcl.2010.05.036","pmid":"20538463","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A Tc-99m labeled triazole peptide binding c-Met receptor kinase was synthesized for tumor imaging, enabling detection of c-Met-positive cancers through nuclear medicine — peptide-based cancer diagnostics.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01640","title":"Concordant and discordant adrenocorticotropin (ACTH) responses induced by growth hormone-releasing peptide-2 (GHRP-2), corticotropin-releasing hormone (CRH) and insulin-induced hypoglycemia in patients with hypothalamopituitary disorders: evidence for direct ACTH releasing activity of GHRP-2.","authors":"Kimura, Takashi; Shimatsu, Akira; Arimura, Hiroshi; Mori, Hideki; Tokitou, Akinori; Fukudome, Michiyo; Nakazaki, Mitsuhiro; Tei, Chuwa","year":2010,"journal":"Endocrine journal, 57(7), 639-44","doi":null,"pmid":"20431231","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GHRP-2, CRF, and desmopressin each produced distinct ACTH response patterns (concordant vs discordant with cortisol), revealing how different peptide stimuli engage the stress axis through different mechanisms.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01641","title":"Ghrelin: more than endogenous growth hormone secretagogue.","authors":"Kojima, Masayasu; Kangawa, Kenji","year":2010,"journal":"Annals of the New York Academy of Sciences, 1200, 140-8","doi":"10.1111/j.1749-6632.2010.05516.x","pmid":"20633142","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Ghrelin's roles extend far beyond GH secretion to include appetite regulation, cardiovascular protection, immune modulation, bone metabolism, and GI motility — a multi-system hormone update.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01642","title":"Recombinant self-assembling peptides as biomaterials for tissue engineering.","authors":"Kyle, Stuart; Aggeli, Amalia; Ingham, Eileen; McPherson, Michael J","year":2010,"journal":"Biomaterials, 31(36), 9395-405","doi":"10.1016/j.biomaterials.2010.08.051","pmid":"20932572","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Recombinant self-assembling peptides designed through genetic engineering create customizable biomaterial scaffolds for tissue engineering — combining biological production with molecular design precision.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01643","title":"Anti-Mullerian hormone (AMH) as a predictive marker in assisted reproductive technology (ART).","authors":"La Marca, A; Sighinolfi, G; Radi, D; Argento, C; Baraldi, E; Artenisio, A Carducci; Stabile, G; Volpe, A","year":2010,"journal":"Human reproduction update, 16(2), 113-30","doi":"10.1093/humupd/dmp036","pmid":"19793843","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01644","title":"Gastrointestinal hormones and the regulation of β-cell mass.","authors":"Lavine, Jeremy A; Attie, Alan D","year":2010,"journal":"Annals of the New York Academy of Sciences, 1212, 41-58","doi":"10.1111/j.1749-6632.2010.05802.x","pmid":"21039588","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GI hormones (GLP-1, GIP, CCK, gastrin) regulate pancreatic beta-cell mass through proliferation and anti-apoptosis, explaining how incretin drugs may preserve insulin production capacity in diabetes.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01645","title":"Role of the ghrelin system in alcoholism: Acting on the growth hormone secretagogue receptor to treat alcohol-related diseases.","authors":"Leggio, L","year":2010,"journal":"Drug news & perspectives, 23(3), 157-66","doi":"10.1358/dnp.2010.23.3.1429490","pmid":"20440417","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The ghrelin system offers a novel therapeutic target for alcoholism — ghrelin receptor antagonists could reduce alcohol craving and consumption by blocking the hunger hormone's reward-promoting effects.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01646","title":"Minireview: kisspeptin/neurokinin B/dynorphin (KNDy) cells of the arcuate nucleus: a central node in the control of gonadotropin-releasing hormone secretion.","authors":"Lehman, Michael N; Coolen, Lique M; Goodman, Robert L","year":2010,"journal":"Endocrinology, 151(8), 3479-89","doi":"10.1210/en.2010-0022","pmid":"20501670","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01647","title":"Food form and portion size affect postprandial appetite sensations and hormonal responses in healthy, nonobese, older adults.","authors":"Leidy, Heather J; Apolzan, John W; Mattes, Richard D; Campbell, Wayne W","year":2010,"journal":"Obesity (Silver Spring, Md.), 18(2), 293-9","doi":"10.1038/oby.2009.217","pmid":"19629055","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Food physical form (liquid vs solid) and portion size independently affected postprandial appetite hormones (GLP-1, PYY, CCK, ghrelin) in older adults — practical meal design matters for appetite control in aging.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01648","title":"Neurotrophic peptides incorporating adamantane improve learning and memory, promote neurogenesis and synaptic plasticity in mice.","authors":"Li, Bin; Wanka, Lukas; Blanchard, Julie; Liu, Fei; Chohan, Muhammad Omar; Iqbal, Khalid; Grundke-Iqbal, Inge","year":2010,"journal":"FEBS letters, 584(15), 3359-65","doi":"10.1016/j.febslet.2010.06.025","pmid":"20600002","tags":[],"studyType":"animal","evidenceStrength":"early","keyFinding":"A designed peptide called P21 (Ac-DGGLAG-NH2), incorporating adamantane to improve brain penetration, enhanced learning, short-term memory, and spatial reference memory in normal adult mice when given peripherally (not requiring brain injection). P21 also stimulated neurogenesis — the birth of new neurons — and promoted their maturation into functional neurons in the dentate gyrus of the hippocampus, the brain region critical for memory formation.","whyItMatters":"Neurotrophins like BDNF and CNTF are powerful brain growth factors that promote neuron survival and new neuron growth, but they're too large to cross the blood-brain barrier as drugs. P21 was designed as a small peptide that mimics neurotrophin effects while being small enough to reach the brain from a peripheral injection. The fact that it enhanced cognition in normal (not diseased) mice suggests potential applications beyond Alzheimer's disease.","specificNumbers":"P21: 6 amino acids (Ac-DGGLAG-NH2) · Enhanced learning + short-term + spatial memory · Increased neurogenesis in dentate gyrus · Peripheral administration · Normal adult C57Bl6 mice","methodology":"P21 peptide was designed incorporating adamantane moiety for improved brain penetration. Normal adult C57Bl6 mice received peripheral P21 administration and were tested for learning and memory using behavioral assays. Neurogenesis was assessed by examining the granular cell layer and subgranular zone of the dentate gyrus for new neuron birth and maturation.","limitations":"Mouse study in normal (non-diseased) animals — effects in Alzheimer's models or humans are unknown. The specific dose, route, and duration of P21 treatment are not detailed in the abstract. Long-term safety of promoting neurogenesis is not addressed. No comparison to existing cognitive enhancers."},{"rthcId":"RPEP-01649","title":"Thymosin alpha 1: biological activities, applications and genetic engineering production.","authors":"Li, Juan; Liu, Chun Hui; Wang, Feng Shan","year":2010,"journal":"Peptides, 31(11), 2151-8","doi":"10.1016/j.peptides.2010.07.026","pmid":"20699109","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Updated comprehensive review of thymosin alpha-1 covering biological activities, clinical applications (hepatitis, cancer, vaccines, HIV), and genetic engineering production methods for commercial manufacturing.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01650","title":"Ghrelin's role as a major regulator of appetite and its other functions in neuroendocrinology.","authors":"Lim, Chung Thong; Kola, Blerina; Korbonits, Márta; Grossman, Ashley B","year":2010,"journal":"Progress in brain research, 182, 189-205","doi":"10.1016/S0079-6123(10)82008-4","pmid":"20541666","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Ghrelin's role as the primary appetite-stimulating hormone is reviewed alongside its neuroendocrine functions including GH release, stress axis interaction, and reproductive regulation — the complete appetite-endocrine picture.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01651","title":"18F-labeled galacto and PEGylated RGD dimers for PET imaging of αvβ3 integrin expression.","authors":"Liu, Shuanglong; Liu, Zhaofei; Chen, Kai; Yan, Yongjun; Watzlowik, Petra; Wester, Hans-Jürgen; Chin, Frederick T; Chen, Xiaoyuan","year":2010,"journal":"Molecular imaging and biology, 12(5), 530-8","doi":"10.1007/s11307-009-0284-2","pmid":"19949981","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01652","title":"Cortistatin attenuates vascular calcification in rats.","authors":"Liu, Yue; Zhou, Ye Bo; Zhang, Gai Gai; Cai, Yan; Duan, Xiao Hui; Teng, Xu; Song, Jun Qiu; Shi, Yi; Tang, Chao Shu; Yin, Xin Hua; Qi, Yong Fen","year":2010,"journal":"Regulatory peptides, 159(1-3), 35-43","doi":"10.1016/j.regpep.2009.09.005","pmid":"19766150","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Cortistatin (a somatostatin-related peptide) attenuated vascular calcification in rats, revealing a protective role against the arterial hardening that causes cardiovascular disease and death.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01653","title":"Cholecystokinin knockout mice are resistant to high-fat diet-induced obesity.","authors":"Lo, Chun-Min; King, Alexandra; Samuelson, Linda C; Kindel, Tammy Lyn; Rider, Therese; Jandacek, Ronald J; Raybould, Helen E; Woods, Stephen C; Tso, Patrick","year":2010,"journal":"Gastroenterology, 138(5), 1997-2005","doi":"10.1053/j.gastro.2010.01.044","pmid":"20117110","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CCK knockout mice were resistant to high-fat diet-induced obesity — paradoxically, losing the satiety hormone CCK protected against weight gain, suggesting CCK has complex metabolic roles beyond simple meal termination.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01654","title":"Thymus hormones as prospective anti-inflammatory agents.","authors":"Lunin, Sergey M; Novoselova, Elena G","year":2010,"journal":"Expert opinion on therapeutic targets, 14(8), 775-86","doi":"10.1517/14728222.2010.499127","pmid":"20536297","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Thymic hormones (thymosin alpha-1, thymulin) show anti-inflammatory properties beyond their known immune-enhancing effects, suppressing inflammatory cytokines and potentially treating chronic inflammatory diseases.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01655","title":"Microbicidal effect of the lactoferrin peptides lactoferricin17-30, lactoferrampin265-284, and lactoferrin chimera on the parasite Entamoeba histolytica.","authors":"López-Soto, Fernando; León-Sicairos, Nidia; Nazmi, Kamran; Bolscher, Jan G; de la Garza, Mireya","year":2010,"journal":"Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine, 23(3), 563-8","doi":"10.1007/s10534-010-9295-3","pmid":"20140481","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Bovine lactoferrin-derived peptides (lactoferricin, lactoferrampin, LFchimera) showed microbicidal activity against Trichomonas vaginalis — extending milk peptide protection to sexually transmitted parasitic infections.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01656","title":"Large randomized study of thymosin alpha 1, interferon alfa, or both in combination with dacarbazine in patients with metastatic melanoma.","authors":"Maio, Michele; Mackiewicz, Andrzej; Testori, Alessandro; Trefzer, Uwe; Ferraresi, Virginia; Jassem, Jacek; Garbe, Claus; Lesimple, Thierry; Guillot, Bernard; Gascon, Pere; Gilde, Katalin; Camerini, Roberto; Cognetti, Francesco","year":2010,"journal":"Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 28(10), 1780-7","doi":"10.1200/JCO.2009.25.5208","pmid":"20194853","tags":["thymosin-alpha-1","melanoma","immunotherapy","cancer"],"studyType":"rct","evidenceStrength":"moderate-high","keyFinding":"In a large randomized trial of 488 patients with metastatic melanoma, adding thymosin alpha 1 (Tα1) to chemotherapy showed promising activity. The two best-performing groups — Tα1 3.2 mg + dacarbazine + interferon, and Tα1 3.2 mg + dacarbazine alone — had more tumor responses (10 and 12, respectively) than the control group (4 responses). Response duration was substantially longer with Tα1 (up to 23.2 months vs. max 8.4 months in controls).\n\nMedian overall survival trended higher with Tα1 (9.4 vs. 6.6 months, HR 0.80, p=0.08) and progression-free survival showed a similar trend (HR 0.80, p=0.06). Neither reached statistical significance. Crucially, Tα1 added no extra toxicity to the treatment regimen.","whyItMatters":"This was one of the largest randomized trials testing thymosin alpha 1 as a cancer immunotherapy, published in the Journal of Clinical Oncology. While the overall survival and PFS differences narrowly missed statistical significance, the improved response rates and longer response durations — with no added toxicity — suggested genuine immunological activity against melanoma. This was notable because it predated the checkpoint immunotherapy revolution and explored a fundamentally different immune-boosting approach.","specificNumbers":"n=488 · 5 treatment arms · Tumor responses: 10-12 (Tα1 groups) vs 4 (control) · Response duration: up to 23.2 mo (Tα1) vs max 8.4 mo (control) · Median OS: 9.4 vs 6.6 months · OS HR 0.80 (p=0.08) · PFS HR 0.80 (p=0.06) · No additional toxicity","methodology":"Randomized, multicenter trial of 488 metastatic melanoma patients assigned to five treatment groups: three groups received dacarbazine + interferon + thymosin alpha 1 at doses of 1.6, 3.2, or 6.4 mg; one group received dacarbazine + Tα1 3.2 mg; and the control received dacarbazine + interferon. Primary endpoint was best overall response at 12 months. Patients observed for up to 24 months.","limitations":"The primary survival endpoints (OS, PFS) did not reach statistical significance (p=0.08 and p=0.06), meaning the survival benefit could be due to chance. The trial predates modern melanoma treatments (checkpoint inhibitors like pembrolizumab), limiting current clinical relevance. Multiple treatment arms in a 488-patient trial reduces statistical power per comparison. Open-label design."},{"rthcId":"RPEP-01657","title":"Neurogenic inflammation of the ocular surface.","authors":"Mantelli, Flavio; Micera, Alessandra; Sacchetti, Marta; Bonini, Stefano","year":2010,"journal":"Current opinion in allergy and clinical immunology, 10(5), 498-504","doi":"10.1097/ACI.0b013e32833e16cc","pmid":"20706114","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Neuropeptides (substance P, CGRP, VIP) mediate neurogenic inflammation on the eye surface, contributing to dry eye, allergic conjunctivitis, and corneal wound healing — the neuroimmune basis of ocular surface disease.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01658","title":"Pharmacokinetics and pharmacodynamics of inhaled GLP-1 (MKC253): proof-of-concept studies in healthy normal volunteers and in patients with type 2 diabetes.","authors":"Marino, M T; Costello, D; Baughman, R; Boss, A; Cassidy, J; Damico, C; van Marle, S; van Vliet, A; Richardson, P C","year":2010,"journal":"Clinical pharmacology and therapeutics, 88(2), 243-50","doi":"10.1038/clpt.2010.85","pmid":"20592721","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01659","title":"Cilengitide: the first anti-angiogenic small molecule drug candidate design, synthesis and clinical evaluation.","authors":"Mas-Moruno, Carlos; Rechenmacher, Florian; Kessler, Horst","year":2010,"journal":"Anti-cancer agents in medicinal chemistry, 10(10), 753-68","doi":null,"pmid":"21269250","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01660","title":"Transcription profile of human lymphocytes following in vitro treatment with thymosin alpha-1.","authors":"Matteucci, Claudia; Minutolo, Antonella; Sinibaldi-Vallebona, Paola; Palamara, Anna Teresa; Rasi, Guido; Mastino, Antonio; Garaci, Enrico","year":2010,"journal":"Annals of the New York Academy of Sciences, 1194, 6-19","doi":"10.1111/j.1749-6632.2010.05484.x","pmid":"20536445","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Thymosin alpha-1 treatment altered expression of hundreds of genes in human lymphocytes, including immune response, signaling, and metabolic genes — the most comprehensive transcriptional view of thymosin alpha-1's immune effects.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01661","title":"Synergistic effects of tethered growth factors and adhesion ligands on DNA synthesis and function of primary hepatocytes cultured on soft synthetic hydrogels.","authors":"Mehta, Geeta; Williams, Courtney M; Alvarez, Luis; Lesniewski, Martha; Kamm, Roger D; Griffith, Linda G","year":2010,"journal":"Biomaterials, 31(17), 4657-71","doi":"10.1016/j.biomaterials.2010.01.138","pmid":"20304480","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Growth factors tethered to self-assembling peptide scaffolds synergistically improved liver cell function (DNA synthesis, albumin, urea) — combining biomaterial design with growth factor delivery for tissue engineering.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01662","title":"Involvement of the peripheral sensory and sympathetic nervous system in the vascular endothelial expression of ICAM-1 and the recruitment of opioid-containing immune cells to inhibit inflammatory pain.","authors":"Mousa, Shaaban A; Shaqura, Mohammed; Brendl, Ute; Al-Khrasani, Mahmoud; Fürst, Susanna; Schäfer, Michael","year":2010,"journal":"Brain, behavior, and immunity, 24(8), 1310-23","doi":"10.1016/j.bbi.2010.06.008","pmid":"20600813","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Peripheral sensory and sympathetic nerves regulated vascular ICAM-1 and selectin expression through neuropeptide release, demonstrating neural-vascular inflammation control relevant to atherosclerosis and inflammatory disease.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01663","title":"Preclinical studies with IRX-2 and thymosin alpha1 in combination therapy.","authors":"Naylor, Paul H; Hadden, John W","year":2010,"journal":"Annals of the New York Academy of Sciences, 1194, 162-8","doi":"10.1111/j.1749-6632.2010.05475.x","pmid":"20536465","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Thymosin alpha-1 combined with IRX-2 (a multi-cytokine biologic) showed enhanced anti-tumor immunity in preclinical models — supporting combination immunotherapy approaches for cancer treatment.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01664","title":"Binding of synthetic peptide TPLVTLFK to nonopioid beta-endorphin receptor on rat brain membranes.","authors":"Nekrasova, Yuliia N; Sadovnikov, Vladimir B; Zolotarev, Yury A; Navolotskaya, Elena V","year":2010,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 16(6), 263-8","doi":"10.1002/psc.1231","pmid":"20474037","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Synthetic peptide TPLVTLFK bound to a non-opioid beta-endorphin receptor on rat brain membranes, confirming the existence of non-classical opioid receptors that mediate endorphin effects beyond pain relief.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01665","title":"Ghrelin: new molecular pathways modulating appetite and adiposity.","authors":"Nogueiras, Ruben; Williams, Lynda M; Dieguez, Carlos","year":2010,"journal":"Obesity facts, 3(5), 285-92","doi":"10.1159/000321265","pmid":"20975294","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Updated review of ghrelin's appetite and adiposity pathways, including newly identified molecular mechanisms for fat accumulation and energy expenditure modulation through hypothalamic and peripheral circuits.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01666","title":"Effect of alginate on satiation, appetite, gastric function, and selected gut satiety hormones in overweight and obesity.","authors":"Odunsi, Suwebatu T; Vázquez-Roque, María I; Camilleri, Michael; Papathanasopoulos, Athanasios; Clark, Matthew M; Wodrich, Lynne; Lempke, Mary; McKinzie, Sanna; Ryks, Michael; Burton, Duane; Zinsmeister, Alan R","year":2010,"journal":"Obesity (Silver Spring, Md.), 18(8), 1579-84","doi":"10.1038/oby.2009.421","pmid":"19960001","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Alginate (seaweed fiber) supplementation increased satiation, reduced appetite, and modified gut hormone responses (GLP-1, PYY, CCK) in overweight/obese humans — a natural fiber supplement for appetite control.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01667","title":"Determination of growth hormone secretagogue pralmorelin (GHRP-2) and its metabolite in human urine by liquid chromatography/electrospray ionization tandem mass spectrometry.","authors":"Okano, Masato; Sato, Mitsuhiko; Ikekita, Ayako; Kageyama, Shinji","year":2010,"journal":"Rapid communications in mass spectrometry : RCM, 24(14), 2046-56","doi":"10.1002/rcm.4619","pmid":"20552695","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"An LC-MS/MS method was developed to detect GHRP-2 (pralmorelin) and its metabolite in human urine for anti-doping purposes — enabling detection of GH peptide use in sports.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01668","title":"Neuropeptide S: a transmitter system in the brain regulating fear and anxiety.","authors":"Pape, Hans-Christian; Jüngling, Kay; Seidenbecher, Thomas; Lesting, Jörg; Reinscheid, Rainer K","year":2010,"journal":"Neuropharmacology, 58(1), 29-34","doi":"10.1016/j.neuropharm.2009.06.001","pmid":"19523478","tags":[],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Neuropeptide S (NPS) has a unique dual action in the brain: it simultaneously increases wakefulness and arousal while producing anxiolytic (anti-anxiety) effects. NPS reduces acute fear responses and modulates long-term fear memory — attenuating contextual fear and enhancing fear extinction.\n\nAt the circuit level, NPS increases glutamate release in the amygdala, particularly at synapses contacting GABAergic interneurons involved in processing fear. NPS-producing neurons are concentrated in a few brainstem clusters, and the NPS receptor is a highly conserved G-protein-coupled receptor. Human genetic studies have linked polymorphisms in the NPS receptor gene to altered sleep behavior and panic disorder.","whyItMatters":"Fear and anxiety disorders affect hundreds of millions of people, and current treatments often cause sedation. NPS is unusual because it reduces fear and anxiety while simultaneously promoting wakefulness — the opposite of benzodiazepines. This dual profile makes the NPS system a compelling target for developing anti-anxiety drugs that don't make patients drowsy.","specificNumbers":"NPS receptor highly conserved across vertebrates · polymorphisms linked to panic disorder · few brainstem neuron clusters produce NPS · stimulates intracellular Ca²⁺ mobilization","methodology":"This is a narrative review synthesizing findings from animal behavioral studies, electrophysiology experiments in amygdala circuits, receptor pharmacology, and human genetic association studies to characterize the NPS transmitter system.","limitations":"This is a review paper, not original research. Most findings about NPS anxiolytic effects come from animal models, and clinical translation to human anxiety disorders has not yet been demonstrated. The genetic associations with panic disorder are correlational."},{"rthcId":"RPEP-01669","title":"Hydrolytic breakdown of lactoferricin by lactic acid bacteria.","authors":"Paul, Moushumi; Somkuti, George A","year":2010,"journal":"Journal of industrial microbiology & biotechnology, 37(2), 173-8","doi":"10.1007/s10295-009-0660-6","pmid":"19924455","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Lactic acid bacteria (probiotics) hydrolyzed lactoferricin, reducing its antimicrobial activity — revealing that the gut microbiome can modify antimicrobial peptide function, with implications for probiotic-peptide interactions.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01670","title":"Appetite and gastrointestinal motility: role of ghrelin-family peptides.","authors":"Perboni, Simona; Inui, Akio","year":2010,"journal":"Clinical nutrition (Edinburgh, Scotland), 29(2), 227-34","doi":"10.1016/j.clnu.2008.10.016","pmid":"19945199","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Ghrelin-family peptides (ghrelin, obestatin, motilin-related) regulate both appetite and GI motility through related receptor systems, with dual-function therapeutic implications for gastroparesis and appetite disorders.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01671","title":"Thymosin alpha1 to harness immunity to pathogens after haploidentical hematopoietic transplantation.","authors":"Perruccio, Katia; Bonifazi, Pierluigi; Topini, Fabiana; Tosti, Antonella; Bozza, Silvia; Aloisi, Teresa; Carotti, Alessandra; Aversa, Franco; Martelli, Massimo F; Romani, Luigina; Velardi, Andrea","year":2010,"journal":"Annals of the New York Academy of Sciences, 1194, 153-61","doi":"10.1111/j.1749-6632.2010.05486.x","pmid":"20536464","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Thymosin alpha-1 enhanced immune reconstitution after haploidentical hematopoietic transplantation, reducing infection risk during the critical immune-depleted period — peptide immunotherapy for transplant patients.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01672","title":"Impact of pentadecapeptide BPC 157 on muscle healing impaired by systemic corticosteroid application.","authors":"Pevec, Danira; Novinscak, Tomislav; Brcic, Luka; Sipos, Kristijan; Jukic, Ivana; Staresinic, Mario; Mise, Sandro; Brcic, Iva; Kolenc, Danijela; Klicek, Robert; Banic, Tihomir; Sever, Marko; Kocijan, Ana; Berkopic, Lidija; Radic, Bozo; Buljat, Gojko; Anic, Tomislav; Zoricic, Ivan; Bojanic, Ivan; Seiwerth, Sven; Sikiric, Predrag","year":2010,"journal":"Medical science monitor : international medical journal of experimental and clinical research, 16(3), BR81-88","doi":null,"pmid":"20190676","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BPC-157 improved muscle healing that was impaired by systemic corticosteroid administration in rats, demonstrating its ability to counteract steroid-induced healing failure in skeletal muscle.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01673","title":"Peptides surviving the simulated gastrointestinal digestion of milk proteins: biological and toxicological implications.","authors":"Picariello, Gianluca; Ferranti, Pasquale; Fierro, Olga; Mamone, Gianfranco; Caira, Simonetta; Di Luccia, Aldo; Monica, Stefano; Addeo, Francesco","year":2010,"journal":"Journal of chromatography. B, Analytical technologies in the biomedical and life sciences, 878(3-4), 295-308","doi":"10.1016/j.jchromb.2009.11.033","pmid":"19962948","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Analysis of peptides surviving simulated GI digestion of milk proteins revealed both beneficial bioactive peptides (opioid, antimicrobial, immunomodulatory) and potentially concerning sequences — digestion determines bioavailability.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01674","title":"Thymosin alpha1: the regulator of regulators?","authors":"Pierluigi, Bonifazi; D'Angelo, Carmen; Fallarino, Francesca; Moretti, Silvia; Zelante, Teresa; Bozza, Silvia; De Luca, Antonella; Bistoni, Francesco; Garaci, Enrico; Romani, Luigina","year":2010,"journal":"Annals of the New York Academy of Sciences, 1194, 1-5","doi":"10.1111/j.1749-6632.2010.05465.x","pmid":"20536444","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Thymosin alpha-1 acts as a 'regulator of regulators' — modulating not just immune cells directly but controlling dendritic cell programming, TLR signaling, and regulatory T-cell generation for balanced immune orchestration.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01675","title":"Selecting GLP-1 agonists in the management of type 2 diabetes: differential pharmacology and therapeutic benefits of liraglutide and exenatide.","authors":"Pinkney, Jonathan; Fox, Thomas; Ranganath, Lakshminarayan","year":2010,"journal":"Therapeutics and clinical risk management, 6, 401-11","doi":null,"pmid":"20856686","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Differential pharmacology comparison of liraglutide and exenatide for T2DM: liraglutide's once-daily dosing, greater HbA1c reduction, and more consistent weight loss versus exenatide's twice-daily profile.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01676","title":"Comparison of midregional pro-atrial natriuretic peptide with N-terminal pro-B-type natriuretic peptide in the diagnosis of heart failure.","authors":"Potocki, M; Breidthardt, T; Reichlin, T; Hartwiger, S; Morgenthaler, N G; Bergmann, A; Noveanu, M; Freidank, H; Taegtmeyer, A B; Wetzel, K; Boldanova, T; Stelzig, C; Bingisser, R; Christ, M; Mueller, C","year":2010,"journal":"Journal of internal medicine, 267(1), 119-29","doi":"10.1111/j.1365-2796.2009.02135.x","pmid":"19570053","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"MR-proANP and NT-proBNP were compared head-to-head for heart failure diagnosis in emergency settings, with both showing excellent diagnostic performance — MR-proANP as a validated alternative.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01677","title":"The gut hormone response following Roux-en-Y gastric bypass: cross-sectional and prospective study.","authors":"Pournaras, Dimitrios J; Osborne, Alan; Hawkins, Simon C; Mahon, David; Ghatei, Mohammad A; Bloom, Steve R; Welbourn, Richard; le Roux, Carel W","year":2010,"journal":"Obesity surgery, 20(1), 56-60","doi":"10.1007/s11695-009-9989-1","pmid":"19826888","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Both cross-sectional and prospective data confirmed dramatic GLP-1, PYY, and ghrelin changes after Roux-en-Y gastric bypass, with sustained hormonal modification explaining long-term surgical weight loss success.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01678","title":"Peripheral endothelin B receptor agonist-induced antinociception involves endogenous opioids in mice.","authors":"Quang, Phuong N; Schmidt, Brian L","year":2010,"journal":"Pain, 149(2), 254-262","doi":"10.1016/j.pain.2010.02.009","pmid":"20206445","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Peripheral endothelin B receptor agonists produced pain relief in mice through triggering endogenous opioid peptide release — another non-opioid drug that works by enlisting the body's own painkillers.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01679","title":"Thuricin CD, a posttranslationally modified bacteriocin with a narrow spectrum of activity against Clostridium difficile.","authors":"Rea, Mary C; Sit, Clarissa S; Clayton, Evelyn; O'Connor, Paula M; Whittal, Randy M; Zheng, Jing; Vederas, John C; Ross, R Paul; Hill, Colin","year":2010,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 107(20), 9352-7","doi":"10.1073/pnas.0913554107","pmid":"20435915","tags":["antimicrobial-peptides","gut-health"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Researchers discovered thuricin CD, a two-component antimicrobial peptide system that kills Clostridium difficile at nanomolar concentrations — including the notoriously virulent ribotype 027 — while leaving most other gut bacteria unharmed. The peptide is produced by Bacillus thuringiensis DPC 6431, a bacterium isolated from a human stool sample.\n\nThuricin CD consists of two separate peptides (Trn-alpha and Trn-beta) that work synergistically — meaning they're far more effective together than either alone. Structural analysis revealed an unusual chemistry: three sulfur-to-alpha-carbon bridges created by posttranslational modifications, a novel structural feature that contributes to the peptide's activity and specificity.","whyItMatters":"C. difficile infection is one of the most serious hospital-acquired infections worldwide, killing an estimated 29,000 Americans annually. Current antibiotic treatments (vancomycin, metronidazole, fidaxomicin) devastate the normal gut flora, often leading to recurrent infections. A narrow-spectrum antimicrobial that kills C. difficile while sparing beneficial gut bacteria would be a game-changer — eliminating the pathogen without destroying the microbiome that normally keeps it in check.","specificNumbers":"","methodology":"Researchers isolated Bacillus thuringiensis DPC 6431 from a human fecal sample and purified the two-component thuricin CD peptide system. They tested activity against a wide panel of clinical C. difficile isolates (including ribotype 027) and other gastrointestinal bacteria. They characterized the peptide structures using infusion tandem mass spectrometry, multidimensional NMR spectroscopy with isotope-labeled peptides, and gene cluster sequencing to identify the biosynthetic machinery.","limitations":"This is an in vitro (laboratory) study — the peptides were not tested in animals or humans. Whether thuricin CD can be delivered to the gut in sufficient concentrations, survive the GI environment, and retain its narrow-spectrum activity in the complex ecosystem of the human microbiome is unknown. Manufacturing two synergistic peptides with unusual posttranslational modifications for clinical use would be technically challenging."},{"rthcId":"RPEP-01680","title":"Long-term dietary restriction influences plasma ghrelin and GOAT mRNA level in rats.","authors":"Reimer, Raylene A; Maurer, Alannah D; Lau, David C W; Auer, Roland N","year":2010,"journal":"Physiology & behavior, 99(5), 605-10","doi":"10.1016/j.physbeh.2010.01.034","pmid":"20149910","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Chronic dietary restriction altered both plasma ghrelin levels and GOAT (the enzyme that activates ghrelin by adding its fatty acid tag) mRNA in rats — calorie restriction reprograms the ghrelin activation system.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01681","title":"Role of urotensin II in health and disease.","authors":"Ross, Bryan; McKendy, Katherine; Giaid, Adel","year":2010,"journal":"American journal of physiology. Regulatory, integrative and comparative physiology, 298(5), R1156-72","doi":"10.1152/ajpregu.00706.2009","pmid":"20421634","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01682","title":"Behavioral effects of neuropeptides in rodent models of depression and anxiety.","authors":"Rotzinger, Susan; Lovejoy, David A; Tan, Laura A","year":2010,"journal":"Peptides, 31(4), 736-56","doi":"10.1016/j.peptides.2009.12.015","pmid":"20026211","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Comprehensive review of neuropeptide behavioral effects in depression and anxiety rodent models: CRF antagonists for anxiolysis, NPY agonists for resilience, and other peptide targets — guiding psychiatric drug development.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01683","title":"A self-assembling peptide acting as an immune adjuvant.","authors":"Rudra, Jai S; Tian, Ye F; Jung, Jangwook P; Collier, Joel H","year":2010,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 107(2), 622-7","doi":"10.1073/pnas.0912124107","pmid":"20080728","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01684","title":"Antihypertensive properties of lactoferricin B-derived peptides.","authors":"Ruiz-Giménez, Pedro; Ibáñez, Aida; Salom, Juan B; Marcos, Jose F; López-Díez, Jose Javier; Vallés, Salvador; Torregrosa, Germán; Alborch, Enrique; Manzanares, Paloma","year":2010,"journal":"Journal of agricultural and food chemistry, 58(11), 6721-7","doi":"10.1021/jf100899u","pmid":"20446662","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Lactoferricin B-derived peptides showed confirmed antihypertensive activity through ACE inhibition and other mechanisms, adding blood pressure management to the milk peptide's antimicrobial and anticancer profiles.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01685","title":"The safety and tolerability of GLP-1 receptor agonists in the treatment of type-2 diabetes.","authors":"Russell-Jones, D","year":2010,"journal":"International journal of clinical practice, 64(10), 1402-14","doi":"10.1111/j.1742-1241.2010.02465.x","pmid":"20716148","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Comprehensive safety review of GLP-1 receptor agonists for T2DM: main concerns are GI side effects (nausea) that diminish with time, with rare pancreatitis and thyroid C-cell concerns under monitoring.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01686","title":"Purification of a peptide from seahorse, that inhibits TPA-induced MMP, iNOS and COX-2 expression through MAPK and NF-kappaB activation, and induces human osteoblastic and chondrocytic differentiation.","authors":"Ryu, BoMi; Qian, Zhong-Ji; Kim, Se-Kwon","year":2010,"journal":"Chemico-biological interactions, 184(3), 413-22","doi":"10.1016/j.cbi.2009.12.003","pmid":"20004183","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A purified seahorse-derived peptide inhibited MMP, iNOS, and COX-2 inflammatory mediators through MAPK and NF-κB pathway suppression — a marine-derived anti-inflammatory peptide with arthritis potential.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01687","title":"SHP-1, a novel peptide isolated from seahorse inhibits collagen release through the suppression of collagenases 1 and 3, nitric oxide products regulated by NF-kappaB/p38 kinase.","authors":"Ryu, BoMi; Qian, Zhong-Ji; Kim, Se-Kwon","year":2010,"journal":"Peptides, 31(1), 79-87","doi":"10.1016/j.peptides.2009.10.019","pmid":"19896517","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"SHP-1, a novel seahorse-derived peptide, suppressed collagenases (MMP-1, MMP-13) and gelatinase (MMP-9), potentially protecting joint cartilage from destruction in arthritis — marine peptide therapy for joint disease.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01688","title":"Y4 receptors and pancreatic polypeptide regulate food intake via hypothalamic orexin and brain-derived neurotropic factor dependent pathways.","authors":"Sainsbury, Amanda; Shi, Yan-Chuan; Zhang, Lei; Aljanova, Aygul; Lin, Zhou; Nguyen, Amy D; Herzog, Herbert; Lin, Shu","year":2010,"journal":"Neuropeptides, 44(3), 261-8","doi":"10.1016/j.npep.2010.01.001","pmid":"20116098","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01689","title":"Fine mapping of pre-S sequence requirements for hepatitis B virus large envelope protein-mediated receptor interaction.","authors":"Schulze, Andreas; Schieck, Alexa; Ni, Yi; Mier, Walter; Urban, Stephan","year":2010,"journal":"Journal of virology, 84(4), 1989-2000","doi":"10.1128/JVI.01902-09","pmid":"20007265","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01690","title":"GIP and GLP-1, the two incretin hormones: Similarities and differences.","authors":"Seino, Yutaka; Fukushima, Mitsuo; Yabe, Daisuke","year":2010,"journal":"Journal of diabetes investigation, 1(1-2), 8-23","doi":"10.1111/j.2040-1124.2010.00022.x","pmid":"24843404","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01691","title":"Comparison of the temporary dynamics of NGF and BDNF gene expression in rat hippocampus, frontal cortex, and retina under Semax action.","authors":"Shadrina, Maria; Kolomin, Timur; Agapova, Tamara; Agniullin, Yan; Shram, Stanislav; Slominsky, Petr; Lymborska, Svetlana; Myasoedov, Nikolay","year":2010,"journal":"Journal of molecular neuroscience : MN, 41(1), 30-5","doi":"10.1007/s12031-009-9270-z","pmid":"19662538","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01692","title":"Roles of hormones in taste signaling.","authors":"Shin, Yu-Kyong; Egan, Josephine M","year":2010,"journal":"Results and problems in cell differentiation, 52, 115-37","doi":"10.1007/978-3-642-14426-4_10","pmid":"20865376","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Gut hormones (GLP-1, PYY, ghrelin, leptin) modulate taste receptor signaling in taste buds, revealing that appetite hormones don't just control how much you eat but also how food TASTES.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01693","title":"Thymosin beta4 and cardiac repair.","authors":"Shrivastava, Santwana; Srivastava, Deepak; Olson, Eric N; DiMaio, J Michael; Bock-Marquette, Ildiko","year":2010,"journal":"Annals of the New York Academy of Sciences, 1194, 87-96","doi":"10.1111/j.1749-6632.2010.05468.x","pmid":"20536454","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01694","title":"Revised Robert's cytoprotection and adaptive cytoprotection and stable gastric pentadecapeptide BPC 157. Possible significance and implications for novel mediator.","authors":"Sikiric, Predrag; Seiwerth, Sven; Brcic, Luka; Sever, Marko; Klicek, Robert; Radic, Bozo; Drmic, Domagoj; Ilic, Spomenko; Kolenc, Danijela","year":2010,"journal":"Current pharmaceutical design, 16(10), 1224-34","doi":null,"pmid":"20166993","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BPC-157's unique cytoprotective properties expand Robert's classical cytoprotection concept, demonstrating prostaglandin-independent protection and adaptive cytoprotection against both exogenous and endogenous irritants.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01695","title":"Low stress reactivity and neuroendocrine factors in the BTBR T+tf/J mouse model of autism.","authors":"Silverman, J L; Yang, M; Turner, S M; Katz, A M; Bell, D B; Koenig, J I; Crawley, J N","year":2010,"journal":"Neuroscience, 171(4), 1197-208","doi":"10.1016/j.neuroscience.2010.09.059","pmid":"20888890","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The BTBR autism model mouse showed reduced stress reactivity and altered neuroendocrine factors (oxytocin, vasopressin, CRF), linking neuropeptide dysregulation to autism-like social behavior deficits.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01696","title":"Angiotensin-receptor blockade and risk of cancer: meta-analysis of randomised controlled trials.","authors":"Sipahi, Ilke; Debanne, Sara M; Rowland, Douglas Y; Simon, Daniel I; Fang, James C","year":2010,"journal":"The Lancet. Oncology, 11(7), 627-36","doi":"10.1016/S1470-2045(10)70106-6","pmid":"20542468","tags":["renin-angiotensin-system","cancer-risk","meta-analysis"],"studyType":"Meta-Analysis of RCTs","evidenceStrength":"Strong","keyFinding":"A meta-analysis of randomized controlled trials involving 61,590 patients found that angiotensin receptor blockers (ARBs) were associated with a modestly increased risk of new cancer diagnosis: 7.2% in ARB groups versus 6.0% in control groups (RR 1.08, P=0.016). When limited to trials with cancer as a prespecified endpoint, the risk was slightly higher (RR 1.11, P=0.001).\n\nAmong specific cancers, only lung cancer showed a significantly increased risk with ARB use (0.9% vs 0.7%, RR 1.25, P=0.01). No significant increase in cancer deaths was observed (1.8% vs 1.6%, P=0.183). Telmisartan was the ARB used in 85.7% of patients in the cancer analysis, so the signal was heavily driven by this specific drug.","whyItMatters":"ARBs are among the most widely prescribed drugs worldwide for hypertension, heart failure, and diabetic kidney disease. The angiotensin II peptide system — which ARBs block — plays roles in cell growth, blood vessel formation, and tumor progression. This Lancet Oncology meta-analysis raised an important safety signal that generated considerable debate and led to regulatory review. While subsequent analyses have largely been reassuring, the study highlights how peptide signaling systems (like the renin-angiotensin system) can have unexpected effects across different organ systems.","specificNumbers":"n=61,590 for new cancer · n=93,515 for cancer deaths · new cancer: 7.2% vs 6.0% (RR 1.08, P=.016) · lung cancer: 0.9% vs 0.7% (RR 1.25, P=.01) · cancer deaths: NS · telmisartan = 85.7% of ARB patients","methodology":"Systematic meta-analysis of randomized controlled trials identified through Medline, Scopus, Cochrane databases, and FDA records. Included trials with at least 100 patients, ≥1 year follow-up, and ARB in at least one arm. Separate analyses were conducted for new cancer occurrence, specific solid organ cancers, and cancer mortality.","limitations":"The cancer signal was heavily driven by telmisartan (85.7% of ARB patients), making it difficult to generalize to all ARBs. Cancer was not the primary endpoint in most included trials, raising concerns about ascertainment and reporting bias. The absolute risk increase was small (~1.2 percentage points). No increase in cancer deaths was observed, suggesting the cancers detected may have been early-stage or incidental. Subsequent larger meta-analyses and regulatory reviews have not confirmed a consistent cancer risk with ARBs as a class."},{"rthcId":"RPEP-01697","title":"Neuropeptide receptors in intestinal disease: physiology and therapeutic potential.","authors":"Snoek, Susanne A; Borensztajn, Keren S; van den Wijngaard, René M; de Jonge, Wouter J","year":2010,"journal":"Current pharmaceutical design, 16(9), 1091-105","doi":null,"pmid":"20030609","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Neuropeptide receptors in the GI tract (VIP, substance P, NPY, CGRP) represent therapeutic targets for IBD, IBS, and other intestinal diseases — the gut's neural peptide system as a drug target landscape.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01698","title":"Non-suicidal self-injurious behavior, endogenous opioids and monoamine neurotransmitters.","authors":"Stanley, Barbara; Sher, Leo; Wilson, Scott; Ekman, Rolf; Huang, Yung-yu; Mann, J John","year":2010,"journal":"Journal of affective disorders, 124(1-2), 134-40","doi":"10.1016/j.jad.2009.10.028","pmid":"19942295","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Non-suicidal self-injury (NSSI) is associated with altered endogenous opioid systems — self-harm may produce opioid release that provides emotional relief, explaining why it becomes addictive despite being painful.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01699","title":"Ghrelin, des-acyl ghrelin and nesfatin-1 in gastric X/A-like cells: role as regulators of food intake and body weight.","authors":"Stengel, Andreas; Goebel, Miriam; Wang, Lixin; Taché, Yvette","year":2010,"journal":"Peptides, 31(2), 357-69","doi":"10.1016/j.peptides.2009.11.019","pmid":"19944123","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Gastric X/A-like cells co-produce ghrelin (appetite-stimulating), des-acyl ghrelin (metabolically active), and nesfatin-1 (appetite-suppressing) — three functionally different peptides from a single endocrine cell type.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01700","title":"Metabolic fate of lactoferricin-based antimicrobial peptides: effect of truncation and incorporation of amino acid analogs on the in vitro metabolic stability.","authors":"Svenson, Johan; Vergote, Valentijn; Karstad, Rasmus; Burvenich, Christian; Svendsen, John S; De Spiegeleer, Bart","year":2010,"journal":"The Journal of pharmacology and experimental therapeutics, 332(3), 1032-9","doi":"10.1124/jpet.109.162826","pmid":"19952307","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Metabolic fate studies of lactoferricin-based peptides revealed truncation and amino acid analog incorporation improve proteolytic stability — guiding design of longer-lasting antimicrobial peptide drugs.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01701","title":"Methods for building quantitative structure-activity relationship (QSAR) descriptors and predictive models for computer-aided design of antimicrobial peptides.","authors":"Taboureau, Olivier","year":2010,"journal":"Methods in molecular biology (Clifton, N.J.), 618, 77-86","doi":"10.1007/978-1-60761-594-1_6","pmid":"20094859","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01702","title":"Kisspeptin signaling in the brain: recent developments and future challenges.","authors":"Tena-Sempere, Manuel","year":2010,"journal":"Molecular and cellular endocrinology, 314(2), 164-9","doi":"10.1016/j.mce.2009.05.004","pmid":"19464345","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Updated review of kisspeptin-GPR54 signaling in the brain: controlling GnRH neuron activity, mediating puberty onset, integrating metabolic and environmental cues for reproductive function.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01703","title":"Hypocretin/orexin and energy expenditure.","authors":"Teske, J A; Billington, C J; Kotz, C M","year":2010,"journal":"Acta physiologica (Oxford, England), 198(3), 303-12","doi":"10.1111/j.1748-1716.2010.02075.x","pmid":"20070282","tags":[],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Orexin/hypocretin neuropeptides — produced by a small group of neurons in the hypothalamus — play a significant role in energy expenditure beyond their well-known function in promoting wakefulness. The review finds that orexin-A (hypocretin-1) has a more potent stimulatory effect on energy expenditure than orexin-B (hypocretin-2).\n\nOrexin-A increases whole-body energy expenditure through three main mechanisms: stimulating physical activity, activating the sympathetic nervous system (which increases heart rate and thermogenesis), and directly boosting metabolic rate. The orexin-1 receptor appears to predominantly mediate behaviors that influence energy expenditure.\n\nThe two orexin receptors (OX1R and OX2R) appear to have both shared and distinct physiological roles, but the orexin-2 receptor's specific contributions remain poorly characterized.","whyItMatters":"Orexin is best known as the 'wakefulness peptide' — its absence causes narcolepsy. But this review reveals an equally important role: regulating how many calories you burn. By increasing physical activity, sympathetic tone, and metabolic rate, orexin may be a key factor in why some people are naturally more active and burn more energy. Understanding this could lead to new approaches for treating obesity that target energy expenditure rather than appetite suppression.","specificNumbers":"2 orexin peptides (A and B) · 2 receptors (OX1R and OX2R) · Orexin-A: stronger effect on energy expenditure · OX1R: primary mediator of activity-related energy expenditure","methodology":"Narrative review synthesizing published research on orexin/hypocretin's role in energy expenditure, including studies of physical activity, sympathetic nervous system activation, and whole-body metabolic rate in animal models.","limitations":"Most evidence comes from animal studies (primarily rodent models). The review acknowledges that orexin-2 receptor function in energy expenditure is poorly understood. Translating these findings to human obesity treatment remains speculative. The review does not include human clinical trial data for orexin-based energy expenditure interventions."},{"rthcId":"RPEP-01704","title":"Dendritic cells transduced with lentiviral vectors expressing VIP differentiate into VIP-secreting tolerogenic-like DCs.","authors":"Toscano, Miguel G; Delgado, Mario; Kong, Weimin; Martin, Francisco; Skarica, Mario; Ganea, Doina","year":2010,"journal":"Molecular therapy : the journal of the American Society of Gene Therapy, 18(5), 1035-45","doi":"10.1038/mt.2009.293","pmid":"20068554","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Dendritic cells transduced with lentiviral VIP vectors became VIP-secreting tolerogenic DCs, creating self-sustaining anti-inflammatory immune cells for autoimmune disease gene therapy.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01705","title":"Traumatic brain injury in mice and pentadecapeptide BPC 157 effect.","authors":"Tudor, Mario; Jandric, Ivan; Marovic, Anton; Gjurasin, Miroslav; Perovic, Darko; Radic, Bozo; Blagaic, Alenka Boban; Kolenc, Danijela; Brcic, Luka; Zarkovic, Kamelija; Seiwerth, Sven; Sikiric, Predrag","year":2010,"journal":"Regulatory peptides, 160(1-3), 26-32","doi":"10.1016/j.regpep.2009.11.012","pmid":"19931318","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BPC-157 showed protective effects against traumatic brain injury in mice, improving neurological outcomes — adding brain trauma protection to its expanding neuroprotective profile.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01706","title":"Thymosin alpha 1: past clinical experience and future promise.","authors":"Tuthill, Cynthia; Rios, Israel; McBeath, Randy","year":2010,"journal":"Annals of the New York Academy of Sciences, 1194, 130-5","doi":"10.1111/j.1749-6632.2010.05482.x","pmid":"20536460","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Updated review of thymosin alpha-1 clinical experience spanning hepatitis B/C, cancer immunotherapy, vaccine adjuvancy, and emerging applications — the most clinically advanced immune peptide drug.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01707","title":"The relationship between tumor necrosis factor-α, brain natriuretic peptide and atrial natriuretic peptide in patients with chronic heart failure.","authors":"Vaz Pérez, Amalia; Doehner, Wolfram; von Haehling, Stephan; Schmidt, Hendrik; Zimmermann, Arabel V; Volk, Hans-Dieter; Anker, Stefan D; Rauchhaus, Mathias","year":2010,"journal":"International journal of cardiology, 141(1), 39-43","doi":"10.1016/j.ijcard.2008.11.146","pmid":"19155075","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"TNF-α correlated with both BNP and ANP levels in cardiac patients, revealing the inflammation-natriuretic peptide connection and supporting anti-inflammatory approaches in heart disease management.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01708","title":"Amino-terminal fragment of C-type natriuretic peptide precursor and C-type natriuretic peptide do not correlate in patients with Chagas disease: role for neutral endopeptidase.","authors":"Wang, Yong; Moreira, Maria da Consolação V; Heringer-Walther, Silvia; Schultheiss, Heinz-Peter; Siems, Wolf-Eberhard; Wessel, Niels; Walther, Thomas","year":2010,"journal":"Journal of cardiovascular pharmacology, 55(1), 62-6","doi":"10.1097/FJC.0b013e3181c37dc2","pmid":"20090473","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"NT-proCNP and CNP levels did not correlate in cardiac patients, reflecting their different tissue sources and clearance — they measure different aspects of vascular biology and should not be used interchangeably.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01709","title":"Pharmacological profile of lixisenatide: A new GLP-1 receptor agonist for the treatment of type 2 diabetes.","authors":"Werner, Ulrich; Haschke, Guido; Herling, Andreas W; Kramer, Werner","year":2010,"journal":"Regulatory peptides, 164(2-3), 58-64","doi":"10.1016/j.regpep.2010.05.008","pmid":"20570597","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Lixisenatide (a new GLP-1 receptor agonist based on exendin-4) showed distinct pharmacological properties from liraglutide/exenatide: stronger post-meal glucose control with convenient once-daily dosing.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01710","title":"Cathelicidins in inflammation and tissue repair: Potential therapeutic applications for gastrointestinal disorders.","authors":"Wu, William Ka Kei; Wong, Clover Ching Man; Li, Zhi Jie; Zhang, Lin; Ren, Shun Xiang; Cho, Chi Hin","year":2010,"journal":"Acta pharmacologica Sinica, 31(9), 1118-22","doi":"10.1038/aps.2010.117","pmid":"20676121","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01711","title":"Lactoferrin-derived peptides and Lactoferricin chimera inhibit virulence factor production and biofilm formation in Pseudomonas aeruginosa.","authors":"Xu, G; Xiong, W; Hu, Q; Zuo, P; Shao, B; Lan, F; Lu, X; Xu, Y; Xiong, S","year":2010,"journal":"Journal of applied microbiology, 109(4), 1311-8","doi":"10.1111/j.1365-2672.2010.04751.x","pmid":"20477900","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Lactoferricin-derived peptides and LFchimera inhibited both biofilm formation and virulence factor production in Pseudomonas aeruginosa — anti-virulence activity that disarms rather than just kills this dangerous pathogen.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01712","title":"Molecular forms of natriuretic peptides in heart failure and their implications.","authors":"Xu-Cai, Ye Olivia; Wu, Qingyu","year":2010,"journal":"Heart (British Cardiac Society), 96(6), 419-24","doi":"10.1136/hrt.2008.164145","pmid":"19451138","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Multiple molecular forms of BNP and NT-proBNP circulate in heart failure (proBNP, glycosylated variants, degradation products), with assay specificity for different forms affecting clinical measurements.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01713","title":"Rikkunshito and 5-HT2C receptor antagonist improve cisplatin-induced anorexia via hypothalamic ghrelin interaction.","authors":"Yakabi, Koji; Kurosawa, Susumu; Tamai, Mitsuo; Yuzurihara, Mitsutoshi; Nahata, Miwa; Ohno, Shino; Ro, Shoki; Kato, Shingo; Aoyama, Toru; Sakurada, Tomoya; Takabayashi, Hidehiko; Hattori, Tomohisa","year":2010,"journal":"Regulatory peptides, 161(1-3), 97-105","doi":"10.1016/j.regpep.2010.02.003","pmid":"20171995","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Rikkunshito (traditional medicine) combined with serotonin 5-HT2C receptor antagonism improved cisplatin-induced appetite loss through hypothalamic ghrelin pathway enhancement — integrating traditional and pharmacological approaches.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01714","title":"Teduglutide, a glucagon-like peptide-2 analog for the treatment of gastrointestinal diseases, including short bowel syndrome.","authors":"Yazbeck, Roger","year":2010,"journal":"Current opinion in molecular therapeutics, 12(6), 798-809","doi":null,"pmid":"21154171","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Teduglutide, a GLP-2 analog, demonstrated clinical benefit for short bowel syndrome by promoting intestinal adaptation and reducing parenteral nutrition dependence — a gut peptide drug for a devastating surgical condition.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01715","title":"Role of the intra-A-chain disulfide bond of insulin-like peptide 3 in binding and activation of its receptor, RXFP2.","authors":"Zhang, Suode; Hughes, Richard A; Bathgate, Ross A D; Shabanpoor, Fazel; Hossain, M Akhter; Lin, Feng; van Lierop, Bianca; Robinson, Andrea J; Wade, John D","year":2010,"journal":"Peptides, 31(9), 1730-6","doi":"10.1016/j.peptides.2010.05.021","pmid":"20570702","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The intra-A-chain disulfide bond of INSL3 was essential for RXFP2 receptor binding and activation, revealing structural requirements for this reproductive peptide's function in fertility and testicular descent.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01716","title":"Effect of loop structure of bovine lactoferricin on apoptosis in Jurkat cells.","authors":"Zhang, Tie-nan; Yang, Wei; Liu, Ning","year":2010,"journal":"Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine, 23(3), 555-61","doi":"10.1007/s10534-010-9324-2","pmid":"20237822","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The loop structure of bovine lactoferricin was critical for inducing apoptosis in Jurkat leukemia cells, with loop disruption eliminating anticancer activity — structural requirements for cancer cell killing.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01717","title":"The three-dimensional nanofiber scaffold culture condition improves viability and function of islets.","authors":"Zhao, Ming; Song, Chun; Zhang, Weihui; Hou, Yan; Huang, Renping; Song, Yimin; Xie, Wanjun; Shi, Yubo; Song, Chunfang","year":2010,"journal":"Journal of biomedical materials research. Part A, 94(3), 667-72","doi":"10.1002/jbm.a.32624","pmid":"20336763","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Three-dimensional peptide nanofiber scaffolds improved pancreatic islet viability and insulin secretion function compared to standard culture — advancing peptide scaffolds for diabetes cell-based therapy.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01718","title":"Treatment with marine collagen peptides modulates glucose and lipid metabolism in Chinese patients with type 2 diabetes mellitus.","authors":"Zhu, Cui-Feng; Li, Guan-Zhi; Peng, Hong-Bin; Zhang, Fan; Chen, Yun; Li, Yong","year":2010,"journal":"Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme, 35(6), 797-804","doi":"10.1139/H10-075","pmid":"21164551","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Marine collagen peptide supplementation improved glucose metabolism and lipid profiles in Chinese type 2 diabetes patients — clinical evidence for collagen peptides as a diabetes dietary supplement.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01719","title":"Progress in corticotropin-releasing factor-1 antagonist development.","authors":"Zorrilla, Eric P; Koob, George F","year":2010,"journal":"Drug discovery today, 15(9-10), 371-83","doi":"10.1016/j.drudis.2010.02.011","pmid":"20206287","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Updated review of CRF-1 receptor antagonist development for anxiety and depression, covering new compounds, clinical trial results, and reasons for mixed success — the continuing quest for stress peptide drugs.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01720","title":"Biocompatibility and bioactivity of designer self-assembling nanofiber scaffold containing FGL motif for rat dorsal root ganglion neurons.","authors":"Zou, Zhenwei; Zheng, Qixin; Wu, Yongchao; Guo, Xiaodong; Yang, Shuhua; Li, Jingfeng; Pan, Haitao","year":2010,"journal":"Journal of biomedical materials research. Part A, 95(4), 1125-31","doi":"10.1002/jbm.a.32910","pmid":"20878982","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A designer peptide nanofiber scaffold containing FGL motif (neural cell adhesion molecule fragment) showed biocompatibility and supported dorsal root ganglion neuron growth — peptide scaffold for nerve repair.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01721","title":"Changes in tissue substance P levels in patients with carpal tunnel syndrome.","authors":"Öztürk, Niyazi; Erin, Nuray; Tüzüner, Serdar","year":2010,"journal":"Neurosurgery, 67(6), 1655-60; discussion 1660-1","doi":"10.1227/NEU.0b013e3181fa7032","pmid":"21107196","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tissue substance P levels were altered in carpal tunnel syndrome patients, with changes correlating with nerve compression severity — suggesting this neuropeptide as a biomarker and potential therapeutic target.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01722","title":"Guevara Aguirre 2011 Laron Cancer","authors":"","year":2011,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01723","title":"Mather 2011 Is Telomere Length","authors":"","year":2011,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01724","title":"Ressler 2011 Pacap Ptsd Sex Specific","authors":"","year":2011,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01725","title":"Viviani 2011 Oxytocin Inhibitory Interneurons Cea","authors":"","year":2011,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01726","title":"Salivary PYY: a putative bypass to satiety.","authors":"Acosta, Andres; Hurtado, Maria D; Gorbatyuk, Oleg; La Sala, Michael; Duncan, David; Aslanidi, George; Campbell-Thompson, Martha; Zhang, Lei; Herzog, Herbert; Voutetakis, Antonis; Baum, Bruce J; Zolotukhin, Sergei","year":2011,"journal":"PloS one, 6(10), e26137","doi":"10.1371/journal.pone.0026137","pmid":"22028819","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"PYY was detected in human saliva with potential as a non-invasive biomarker for satiety status, bypassing blood draws — salivary appetite hormone monitoring.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01727","title":"MK-0677 (ibutamoren mesylate) for the treatment of patients recovering from hip fracture: a multicenter, randomized, placebo-controlled phase IIb study.","authors":"Adunsky, Abraham; Chandler, Julie; Heyden, Norman; Lutkiewicz, Jeannine; Scott, Boyd B; Berd, Yuliya; Liu, Nancy; Papanicolaou, Dimitris A","year":2011,"journal":"Archives of gerontology and geriatrics, 53(2), 183-9","doi":"10.1016/j.archger.2010.10.004","pmid":"21067829","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 123 elderly hip fracture patients randomized to MK-677 (25 mg/day) or placebo for 24 weeks, MK-677 significantly increased IGF-1 levels by 51.4 ng/ml compared to placebo (p < 0.001). Gait speed showed a modest but significant improvement (0.7-score difference, p = 0.011). However, stair climbing power did not significantly improve (12.5 W increase, p = 0.292), and several other functional measures showed no benefit.\n\nThe MK-0677 group had fewer falls than placebo, though this did not reach statistical significance (p = 0.096). Critically, the trial was terminated early due to a safety signal of congestive heart failure in a limited number of treated patients, leading to the conclusion that MK-677 has an unfavorable risk-benefit profile in elderly hip fracture patients.","whyItMatters":"MK-677 (ibutamoren) is one of the most popular growth hormone secretagogues in the peptide community. This trial provides critical safety data showing that raising IGF-1 doesn't automatically translate to functional improvement, and that MK-677 can cause serious cardiac side effects in vulnerable elderly patients. It's a cautionary study for anyone considering MK-677, particularly older adults.","specificNumbers":"","methodology":"This was a multicenter, randomized, double-blind, placebo-controlled Phase IIb study. 123 elderly hip fracture patients were randomized to receive either 25 mg/day of oral MK-677 (n=62) or placebo (n=61). Primary outcomes were objective functional performance measures (stair climbing power, gait speed, and others) and blood IGF-1 levels, assessed over 24 weeks.","limitations":"The trial was terminated early due to safety concerns, which means the study was underpowered to detect all potential functional benefits. The sample size of 123 is modest. The study focused on a specific elderly population recovering from hip fracture, and results may not apply to younger or healthier MK-677 users. The specific number of heart failure cases and their clinical details are not fully described in the abstract."},{"rthcId":"RPEP-01728","title":"C- and N-truncated antimicrobial peptides from LFampin 265 - 284: Biophysical versus microbiology results.","authors":"Adão, Regina; Nazmi, Kamran; Bolscher, Jan G M; Bastos, Margarida","year":2011,"journal":"Journal of pharmacy & bioallied sciences, 3(1), 60-9","doi":"10.4103/0975-7406.76467","pmid":"21430955","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Systematic C- and N-terminal truncation of lactoferrampin (LFampin 265-284) revealed the minimal active sequence needed for antimicrobial activity versus biophysical membrane interaction — not all structure-activity matches.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01729","title":"Ghrelin acylation and metabolic control.","authors":"Al Massadi, O; Tschöp, M H; Tong, J","year":2011,"journal":"Peptides, 32(11), 2301-8","doi":"10.1016/j.peptides.2011.08.020","pmid":"21893140","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Ghrelin's octanoyl modification by GOAT enzyme determines its metabolic activity, with acylation status differentially regulating GH release, appetite, and glucose metabolism — acylation as a therapeutic control point.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01730","title":"Antibacterial peptides derived from caprine whey proteins, by digestion with human gastrointestinal juice.","authors":"Almaas, Hilde; Eriksen, Ellen; Sekse, Camilla; Comi, Irene; Flengsrud, Ragnar; Holm, Halvor; Jensen, Einar; Jacobsen, Morten; Langsrud, Thor; Vegarud, Gerd E","year":2011,"journal":"The British journal of nutrition, 106(6), 896-905","doi":"10.1017/S0007114511001085","pmid":"21554806","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Digestion of caprine (goat) whey proteins with human gastrointestinal juice released antibacterial peptides active against foodborne pathogens — dairy digestion generates natural antimicrobial protection.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01731","title":"Biphasic peptide amphiphile nanomatrix embedded with hydroxyapatite nanoparticles for stimulated osteoinductive response.","authors":"Anderson, Joel M; Patterson, Jessica L; Vines, Jeremy B; Javed, Amjad; Gilbert, Shawn R; Jun, Ho-Wook","year":2011,"journal":"ACS nano, 5(12), 9463-79","doi":"10.1021/nn203247m","pmid":"22077993","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Biphasic peptide amphiphile nanomatrix embedded with hydroxyapatite nanoparticles stimulated osteogenic differentiation of mesenchymal stem cells — an optimized bone-regenerating peptide scaffold.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01732","title":"Multiple peptide resistance factor (MprF)-mediated Resistance of Staphylococcus aureus against antimicrobial peptides coincides with a modulated peptide interaction with artificial membranes comprising lysyl-phosphatidylglycerol.","authors":"Andrä, Jörg; Goldmann, Torsten; Ernst, Christoph M; Peschel, Andreas; Gutsmann, Thomas","year":2011,"journal":"The Journal of biological chemistry, 286(21), 18692-700","doi":"10.1074/jbc.M111.226886","pmid":"21474443","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01733","title":"Neuropeptides in lower urinary tract function.","authors":"Arms, Lauren; Vizzard, Margaret A","year":2011,"journal":"Handbook of experimental pharmacology, 395-423","doi":"10.1007/978-3-642-16499-6_19","pmid":"21290237","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Neuropeptides (substance P, CGRP, VIP, NPY) regulate lower urinary tract function including bladder contractility, urine storage, and micturition, with implications for overactive bladder and interstitial cystitis treatment.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01734","title":"Clinical implications of exenatide as a twice-daily or once-weekly therapy for type 2 diabetes.","authors":"Aroda, Vanita R; DeYoung, Mary Beth","year":2011,"journal":"Postgraduate medicine, 123(5), 228-38","doi":"10.3810/pgm.2011.09.2479","pmid":"21904106","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Exenatide once-weekly (long-acting release) showed superior HbA1c reduction and comparable weight loss to twice-daily with improved patient convenience — advancing toward the weekly injection paradigm for GLP-1 drugs.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01735","title":"The safety and tolerability of GLP-1 receptor agonists in the treatment of type 2 diabetes: a review.","authors":"Aroda, Vanita R; Ratner, Robert","year":2011,"journal":"Diabetes/metabolism research and reviews, 27(6), 528-42","doi":"10.1002/dmrr.1202","pmid":"21484979","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Updated 2011 safety review of GLP-1 receptor agonists: GI side effects (nausea, vomiting) are most common but diminish over time; pancreatitis and thyroid concerns addressed with monitoring recommendations.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01736","title":"Antiviral activity and increased host defense against influenza infection elicited by the human cathelicidin LL-37.","authors":"Barlow, Peter G; Svoboda, Pavel; Mackellar, Annie; Nash, Anthony A; York, Ian A; Pohl, Jan; Davidson, Donald J; Donis, Ruben O","year":2011,"journal":"PloS one, 6(10), e25333","doi":"10.1371/journal.pone.0025333","pmid":"22031815","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01737","title":"Activation of spinal mu- and delta-opioid receptors potently inhibits substance P release induced by peripheral noxious stimuli.","authors":"Beaudry, Hélène; Dubois, Dave; Gendron, Louis","year":2011,"journal":"The Journal of neuroscience : the official journal of the Society for Neuroscience, 31(37), 13068-77","doi":"10.1523/JNEUROSCI.1817-11.2011","pmid":"21917790","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Spinal mu- and delta-opioid receptor activation potently inhibited substance P release from peripheral nociceptive nerves, revealing a specific presynaptic mechanism for spinal opioid-mediated pain suppression.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01738","title":"Paneth cells, antimicrobial peptides and maintenance of intestinal homeostasis.","authors":"Bevins, Charles L; Salzman, Nita H","year":2011,"journal":"Nature reviews. Microbiology, 9(5), 356-68","doi":"10.1038/nrmicro2546","pmid":"21423246","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01739","title":"Peripheral inflammation alters desensitization of substance P-evoked current in rat dorsal root ganglion neurons.","authors":"Bie, Bihua; Zhao, Zhi-Qi","year":2011,"journal":"European journal of pharmacology, 670(2-3), 495-9","doi":"10.1016/j.ejphar.2011.09.004","pmid":"21951965","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Peripheral inflammation altered the desensitization of substance P-evoked currents in dorsal root ganglion neurons, explaining why inflamed tissue has enhanced pain sensitivity through neuropeptide receptor changes.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01740","title":"Chemical synthesis of hydrocarbon-stapled peptides for protein interaction research and therapeutic targeting.","authors":"Bird, Gregory H; Crannell, W Christian; Walensky, Loren D","year":2011,"journal":"Current protocols in chemical biology, 3(3), 99-117","doi":"10.1002/9780470559277.ch110042","pmid":"23801563","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Detailed methods for synthesizing hydrocarbon-stapled peptides for protein-protein interaction research and therapeutic targeting — enabling the growing field of stapled peptide drug development.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01741","title":"Liraglutide: a review of the first once-daily GLP-1 receptor agonist.","authors":"Bode, Bruce","year":2011,"journal":"The American journal of managed care, 17(2 Suppl), S59-70","doi":null,"pmid":"21517658","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Comprehensive review of liraglutide — the first once-daily GLP-1 receptor agonist — covering its pharmacology, clinical trial results, weight loss effects, and cardiovascular safety data.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01742","title":"Relation of natriuretic peptide concentrations to central sleep apnea in patients with heart failure.","authors":"Calvin, Andrew D; Somers, Virend K; van der Walt, Christelle; Scott, Christopher G; Olson, Lyle J","year":2011,"journal":"Chest, 140(6), 1517-1523","doi":"10.1378/chest.10-2472","pmid":"21636668","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Natriuretic peptide concentrations correlated with central sleep apnea severity in heart failure patients, with higher BNP identifying patients at risk for this dangerous breathing disorder during sleep.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01743","title":"Engineering of conotoxins for the treatment of pain.","authors":"Carstens, Bodil B; Clark, Richard J; Daly, Norelle L; Harvey, Peta J; Kaas, Quentin; Craik, David J","year":2011,"journal":"Current pharmaceutical design, 17(38), 4242-53","doi":null,"pmid":"22204425","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01744","title":"Phage display of combinatorial peptide libraries: application to antiviral research.","authors":"Castel, Guillaume; Chtéoui, Mohamed; Heyd, Bernadette; Tordo, Noël","year":2011,"journal":"Molecules (Basel, Switzerland), 16(5), 3499-518","doi":"10.3390/molecules16053499","pmid":"21522083","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01745","title":"In vivo production of mineralised tissue pieces for clinical use: a qualitative pilot study using human dental pulp cell.","authors":"Chan, B; Wong, R W K; Rabie, B","year":2011,"journal":"International journal of oral and maxillofacial surgery, 40(6), 612-20","doi":"10.1016/j.ijom.2011.01.008","pmid":"21353764","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Human dental pulp cells in self-assembling peptide scaffolds produced mineralized tissue suitable for dental repair in vivo — practical regenerative dentistry using peptide biomaterials.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01746","title":"The promoting effect of pentadecapeptide BPC 157 on tendon healing involves tendon outgrowth, cell survival, and cell migration.","authors":"Chang, Chung-Hsun; Tsai, Wen-Chung; Lin, Miao-Sui; Hsu, Ya-Hui; Pang, Jong-Hwei Su","year":2011,"journal":"Journal of applied physiology (Bethesda, Md. : 1985), 110(3), 774-80","doi":"10.1152/japplphysiol.00945.2010","pmid":"21030672","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BPC-157's tendon healing mechanism involves promoting tendon cell outgrowth from explants, enhancing cell survival against oxidative stress, and stimulating cell migration — triple cellular mechanism for tendon repair.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01747","title":"Enhancement of dentate gyrus neurogenesis, dendritic and synaptic plasticity and memory by a neurotrophic peptide.","authors":"Chohan, Muhammad Omar; Li, Bin; Blanchard, Julie; Tung, Yunn-Chyn; Heaney, Agnes T; Rabe, Ausma; Iqbal, Khalid; Grundke-Iqbal, Inge","year":2011,"journal":"Neurobiology of aging, 32(8), 1420-34","doi":"10.1016/j.neurobiolaging.2009.08.008","pmid":"19767127","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01748","title":"Blood pressure lowering effect of lactotripeptides assumed as functional foods: a meta-analysis of current available clinical trials.","authors":"Cicero, A F G; Gerocarni, B; Laghi, L; Borghi, C","year":2011,"journal":"Journal of human hypertension, 25(7), 425-36","doi":"10.1038/jhh.2010.85","pmid":"20811398","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01749","title":"3D culture of adult mouse neural stem cells within functionalized self-assembling peptide scaffolds.","authors":"Cunha, Carla; Panseri, Silvia; Villa, Omar; Silva, Diego; Gelain, Fabrizio","year":2011,"journal":"International journal of nanomedicine, 6, 943-55","doi":"10.2147/IJN.S17292","pmid":"21720506","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Functionalized self-assembling peptide scaffolds supported adult mouse neural stem cell survival, proliferation, and differentiation in 3D culture — advancing peptide scaffolds for neural regenerative medicine.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01750","title":"The role of a pre-load beverage on gastric volume and food intake: comparison between non-caloric carbonated and non-carbonated beverage.","authors":"Cuomo, Rosario; Savarese, Maria Flavia; Sarnelli, Giovanni; Nicolai, Emanuele; Aragri, Adriana; Cirillo, Carla; Vozzella, Letizia; Zito, Francesco Paolo; Verlezza, Viviana; Efficie, Eleonora; Buyckx, Maxime","year":2011,"journal":"Nutrition journal, 10, 114","doi":"10.1186/1475-2891-10-114","pmid":"21999723","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Pre-meal carbonated vs non-carbonated water differently affected gastric volume and appetite hormones (GLP-1, PYY, ghrelin) in healthy subjects — even water properties influence satiety signaling.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01751","title":"Mitochondrial targeted antioxidant Peptide ameliorates hypertensive cardiomyopathy.","authors":"Dai, Dao-Fu; Chen, Tony; Szeto, Hazel; Nieves-Cintrón, Madeline; Kutyavin, Vassily; Santana, Luis F; Rabinovitch, Peter S","year":2011,"journal":"Journal of the American College of Cardiology, 58(1), 73-82","doi":"10.1016/j.jacc.2010.12.044","pmid":"21620606","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The mitochondria-targeted antioxidant peptide SS-31 ameliorated hypertensive cardiomyopathy in rats, reducing cardiac fibrosis, hypertrophy, and diastolic dysfunction — protecting the heart from high blood pressure damage.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01752","title":"Thirty years of research on atrial natriuretic factor: historical background and emerging concepts.","authors":"de Bold, Adolfo J","year":2011,"journal":"Canadian journal of physiology and pharmacology, 89(8), 527-31","doi":"10.1139/y11-019","pmid":"21671768","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01753","title":"Dendroaspis natriuretic peptide and the designer natriuretic peptide, CD-NP, are resistant to proteolytic inactivation.","authors":"Dickey, Deborah M; Potter, Lincoln R","year":2011,"journal":"Journal of molecular and cellular cardiology, 51(1), 67-71","doi":"10.1016/j.yjmcc.2011.03.013","pmid":"21459096","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A designer natriuretic peptide (CD-NP) combining CNP with dendroaspis NP sequences showed enhanced resistance to neprilysin and other proteases while maintaining biological activity — engineered peptide drugs lasting longer.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01754","title":"PET imaging of αvβ₃ integrin expression in tumours with ⁶⁸Ga-labelled mono-, di- and tetrameric RGD peptides.","authors":"Dijkgraaf, Ingrid; Yim, Cheng-Bin; Franssen, Gerben M; Schuit, Robert C; Luurtsema, Gert; Liu, Shuang; Oyen, Wim J G; Boerman, Otto C","year":2011,"journal":"European journal of nuclear medicine and molecular imaging, 38(1), 128-37","doi":"10.1007/s00259-010-1615-x","pmid":"20857099","tags":["rgd-peptide","pet-imaging","gallium-68"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"Gallium-68-labeled RGD peptides in monomeric, dimeric, and tetrameric forms were tested for their ability to bind αvβ3 integrin and image tumors using PET scanning. The tetrameric version had the highest binding affinity (IC50 of 1.74 nM) and the best tumor uptake (7.11% injected dose per gram at 2 hours). Performance scaled consistently: tetramer > dimer > monomer. The gallium-68 labeled versions performed comparably to indium-111 labeled versions, and all forms produced clear PET images of tumors in mice.","whyItMatters":"αvβ3 integrin is overexpressed on tumor blood vessels and some cancer cells, making it an attractive target for cancer imaging. This study showed that linking multiple copies of the tumor-targeting RGD peptide together (multimerization) progressively improves both binding strength and tumor uptake. The gallium-68 label is ideal for PET scanning because of its short half-life and availability from generators, making it practical for clinical use without a cyclotron.","specificNumbers":"IC50: monomer 23.9 nM · dimer 8.99 nM · tetramer 1.74 nM · Tumor uptake at 2h: monomer 3.30%ID/g · dimer 5.24%ID/g · tetramer 7.11%ID/g","methodology":"Researchers synthesized mono-, di-, and tetrameric RGD peptides conjugated with the chelator DOTA and labeled them with gallium-68. They measured binding affinity using competitive binding assays, then injected the peptides into mice bearing SK-RC-52 renal cell carcinoma tumors. Biodistribution was measured at 2 hours post-injection, and microPET/CT images were acquired.","limitations":"This was an animal study using a single tumor model (renal cell carcinoma xenograft), which may not represent all tumor types. Only one time point (2 hours) was reported for biodistribution. Kidney uptake, which can be problematic for peptide-based imaging agents, was not discussed in the abstract. No human data were presented."},{"rthcId":"RPEP-01755","title":"Peptoids: bio-inspired polymers as potential pharmaceuticals.","authors":"Dohm, Michelle T; Kapoor, Rinki; Barron, Annelise E","year":2011,"journal":"Current pharmaceutical design, 17(25), 2732-47","doi":null,"pmid":"21728985","tags":["peptoids","peptidomimetics"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Peptoids are synthetic molecules with a peptide-like backbone but with side chains attached to nitrogen instead of carbon, making them completely resistant to protease degradation — the main reason natural peptides break down so quickly in the body. Sequences up to 50 units long can be synthesized with precise control over composition and diverse side chain chemistry.\n\nThe review covers therapeutic applications across four areas: lung surfactant replacement therapy, antimicrobial agents, cancer therapeutics, and diagnostics. Peptoids have demonstrated bioactivity both as protein mimics and as replacements for small molecule drugs, with particular promise in lipid-associated applications where their protease resistance gives them a major advantage over natural peptides.","whyItMatters":"The biggest problem with peptide drugs is that the body destroys them within minutes. Peptoids solve this fundamental limitation by subtly rearranging the molecular structure to make it invisible to proteases while retaining peptide-like biological activity. If peptoids can replicate peptide functions with dramatically improved stability, they could unlock therapeutic applications that peptides alone cannot achieve.","specificNumbers":"up to 50 units in length · complete protease resistance · invented early 1990s · N-substituted glycine backbone","methodology":"Comprehensive review of peptoid research advances covering synthesis methods, structural characterization, and therapeutic applications in lung surfactant therapy, antimicrobial agents, cancer, and diagnostics, with emphasis on in vitro and in vivo studies.","limitations":"As a review, this synthesizes existing research without new experimental data. While peptoids show promise in multiple therapeutic areas, most applications remain preclinical. The structural landscape of peptoids is less well-defined than that of peptides, making rational design more challenging. The relationship between peptoid structure and biological function is still being elucidated."},{"rthcId":"RPEP-01756","title":"Small lytic peptides escape the inhibitory effect of heparan sulfate on the surface of cancer cells.","authors":"Fadnes, Bodil; Uhlin-Hansen, Lars; Lindin, Inger; Rekdal, Øystein","year":2011,"journal":"BMC cancer, 11, 116","doi":"10.1186/1471-2407-11-116","pmid":"21453492","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Smaller lytic anticancer peptides evaded the heparan sulfate barrier on cancer cell surfaces that inhibited larger peptides — size optimization enables effective cancer cell membrane disruption despite surface shielding.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01757","title":"Chemical synthesis of cell-permeable apoptotic peptides from in vivo produced proteins.","authors":"Fricke, Thomas; Mart, Robert J; Watkins, Catherine L; Wiltshire, Marie; Errington, Rachel J; Smith, Paul J; Jones, Arwyn T; Allemann, Rudolf K","year":2011,"journal":"Bioconjugate chemistry, 22(9), 1763-7","doi":"10.1021/bc200338u","pmid":"21823633","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Cell-permeable apoptotic peptides were chemically synthesized from in-vivo-produced protein sequences and shown to induce cancer cell death — converting natural death signals into synthetic cancer drugs.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01758","title":"The novel role of cathepsin L for neuropeptide production illustrated by research strategies in chemical biology with protease gene knockout and expression.","authors":"Funkelstein, Lydiane; Hook, Vivian","year":2011,"journal":"Methods in molecular biology (Clifton, N.J.), 768, 107-25","doi":"10.1007/978-1-61779-204-5_5","pmid":"21805239","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Cathepsin L's novel role in neuropeptide biosynthesis was characterized using chemical biology approaches, establishing it as the key protease for producing active neuropeptides from precursor proteins in secretory vesicles.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01759","title":"Scaffolds for dental pulp tissue engineering.","authors":"Galler, K M; D'Souza, R N; Hartgerink, J D; Schmalz, G","year":2011,"journal":"Advances in dental research, 23(3), 333-9","doi":"10.1177/0022034511405326","pmid":"21677088","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Review of dental pulp regeneration scaffolds including self-assembling peptide hydrogels, collagen, and synthetic polymers — peptide scaffolds offering unique advantages for this dental tissue engineering application.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01760","title":"Weight and metabolic effects of CPAP in obstructive sleep apnea patients with obesity.","authors":"Garcia, Jose M; Sharafkhaneh, Hossein; Hirshkowitz, Max; Elkhatib, Rania; Sharafkhaneh, Amir","year":2011,"journal":"Respiratory research, 12(1), 80","doi":"10.1186/1465-9921-12-80","pmid":"21676224","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CPAP treatment for obstructive sleep apnea affected weight, metabolic parameters, and appetite-regulating hormones (ghrelin, leptin, adiponectin) in obese patients — treating breathing may help weight management.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01761","title":"Direct induction of CCK and GLP-1 release from murine endocrine cells by intact dietary proteins.","authors":"Geraedts, Maartje C P; Troost, Freddy J; Fischer, Marc A J G; Edens, Luppo; Saris, Wim H M","year":2011,"journal":"Molecular nutrition & food research, 55(3), 476-84","doi":"10.1002/mnfr.201000142","pmid":"20938986","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Intact (not just digested) dietary proteins directly stimulated CCK and GLP-1 release from murine enteroendocrine cells, demonstrating that protein sensing in the gut begins before complete digestion.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01762","title":"Intraduodenal administration of intact pea protein effectively reduces food intake in both lean and obese male subjects.","authors":"Geraedts, Maartje C P; Troost, Freddy J; Munsters, Marjet J M; Stegen, Jos H C H; de Ridder, Rogier J; Conchillo, Jose M; Kruimel, Joanna W; Masclee, Ad A M; Saris, Wim H M","year":2011,"journal":"PloS one, 6(9), e24878","doi":"10.1371/journal.pone.0024878","pmid":"21931864","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Intraduodenal intact pea protein effectively reduced food intake in both lean and obese male subjects, with satiety hormone responses confirming protein's appetite-suppressing effect acts in the small intestine.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01763","title":"The role of the gut sweet taste receptor in regulating GLP-1, PYY, and CCK release in humans.","authors":"Gerspach, A C; Steinert, R E; Schönenberger, L; Graber-Maier, A; Beglinger, C","year":2011,"journal":"American journal of physiology. Endocrinology and metabolism, 301(2), E317-25","doi":"10.1152/ajpendo.00077.2011","pmid":"21540445","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Sweet taste receptors in the human gut regulated GLP-1, PYY, and CCK release in response to intragastric glucose, with blocking sweet taste reducing satiety hormone output — taste receptors as gut hormone triggers.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01764","title":"Atrial natriuretic peptides in heart failure: pathophysiological significance, diagnostic and prognostic value.","authors":"Ghosh, Nina; Haddad, Haissam","year":2011,"journal":"Canadian journal of physiology and pharmacology, 89(8), 587-91","doi":"10.1139/y11-040","pmid":"21806511","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Updated review of ANP's role in heart failure: pathophysiological production, diagnostic utility including MR-proANP, and prognostic value — ANP's clinical applications alongside the dominant BNP.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01765","title":"NAP (davunetide) provides functional and structural neuroprotection.","authors":"Gozes, Illana","year":2011,"journal":"Current pharmaceutical design, 17(10), 1040-4","doi":null,"pmid":"21524250","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01766","title":"Insulin and growth hormone-releasing peptide-6 (GHRP-6) have differential beneficial effects on cell turnover in the pituitary, hypothalamus and cerebellum of streptozotocin (STZ)-induced diabetic rats.","authors":"Granado, Miriam; García-Cáceres, Cristina; Tuda, María; Frago, Laura M; Chowen, Julie A; Argente, Jesús","year":2011,"journal":"Molecular and cellular endocrinology, 337(1-2), 101-13","doi":"10.1016/j.mce.2011.02.002","pmid":"21352888","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Insulin and GHRP-6 had differential beneficial effects on pituitary cell turnover in diabetic rats: insulin through anti-apoptosis, GHRP-6 through proliferation — different mechanisms for restoring pituitary health.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01767","title":"Substance P-induced skin inflammation is not modulated by a single dose of sitagliptin in human volunteers.","authors":"Grouzmann, Eric; Bigliardi, Paul; Appenzeller, Monique; Pannatier, André; Buclin, Thierry","year":2011,"journal":"Biological chemistry, 392(3), 217-21","doi":"10.1515/BC.2011.003","pmid":"21194357","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Single-dose sitagliptin (DPP-4 inhibitor) did not modulate substance P-induced skin inflammation in healthy volunteers, despite DPP-4 degrading substance P — acute dosing may be insufficient for anti-inflammatory effects.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01768","title":"Cerebrolysin in vascular dementia: improvement of clinical outcome in a randomized, double-blind, placebo-controlled multicenter trial.","authors":"Guekht, Alla B; Moessler, Herbert; Novak, Philipp H; Gusev, Evgenyi I","year":2011,"journal":"Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association, 20(4), 310-8","doi":"10.1016/j.jstrokecerebrovasdis.2010.01.012","pmid":"20656516","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Cerebrolysin produced statistically significant improvements on both primary endpoints in vascular dementia patients. Cognitive scores (ADAS-cog+) improved by 10.6 points in the cerebrolysin group versus 4.4 points with placebo (P<0.0001). Overall clinical functioning (CIBIC+) also showed significant improvement (P<0.0001).\n\nResponder analyses were particularly striking: 82.1% of cerebrolysin patients achieved meaningful cognitive improvement (≥4-point ADAS-cog+ change) versus 52.2% on placebo. The combined response rate — improvement on both cognition and overall function — was 67.5% versus 27.0%. The odds ratio for achieving a favorable combined response with cerebrolysin was 5.63 (P<0.05), indicating patients were more than five times as likely to respond to treatment.","whyItMatters":"Vascular dementia is the second most common form of dementia after Alzheimer's disease, yet no drug has been approved by the FDA or EMA to treat it. This leaves millions of patients without effective pharmacotherapy. This trial provides some of the strongest evidence that cerebrolysin — a neurotrophic peptide preparation — can meaningfully improve cognition and daily functioning in these patients, potentially filling a critical treatment gap.","specificNumbers":"","methodology":"This was a multicenter, double-blind, placebo-controlled, randomized trial involving 242 patients meeting diagnostic criteria for vascular dementia. Patients received either intravenous cerebrolysin 20 mL or placebo once daily, administered over two treatment cycles as add-on therapy to aspirin. The primary endpoint was a combined measure of cognition (ADAS-cog+) and overall clinical functioning (CIBIC+) at 24 weeks.","limitations":"The trial enrolled 242 patients, which is moderate but not large by modern standards. The study was conducted in European centers and may not generalize to all populations. Cerebrolysin requires daily intravenous infusions, which is a significant practical barrier compared to oral medications. The 24-week follow-up does not address whether benefits persist long-term. The manufacturer (EBEWE Pharma) was involved in the study, which could introduce bias."},{"rthcId":"RPEP-01769","title":"Neuroendocrine activation and diagnostics in pulmonary embolism: Translational studies.","authors":"Gutte, Henrik","year":2011,"journal":"Danish medical bulletin, 58(3), B4258","doi":null,"pmid":"21371407","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Natriuretic peptides and other neuroendocrine markers help diagnose and risk-stratify pulmonary embolism by detecting right ventricular strain — translational biomarker studies for PE management.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01770","title":"Nicotine and endogenous opioids: neurochemical and pharmacological evidence.","authors":"Hadjiconstantinou, Maria; Neff, Norton H","year":2011,"journal":"Neuropharmacology, 60(7-8), 1209-20","doi":"10.1016/j.neuropharm.2010.11.010","pmid":"21108953","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Comprehensive review of nicotine-opioid interactions: nicotine releases endogenous opioids, modulates opioid receptor function, and shares reward pathways — explaining co-addiction and nicotine's pain-modifying effects.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01771","title":"Analysis of cyclotides in Viola ignobilis by Nano liquid chromatography fourier transform mass spectrometry.","authors":"Hashempour, Hossein; Ghassempour, Alireza; Daly, Norelle L; Spengler, Bernhard; Römpp, Andreas","year":2011,"journal":"Protein and peptide letters, 18(7), 747-52","doi":null,"pmid":"21413917","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Nano-LC Fourier transform MS analysis of Viola ignobilis identified novel cyclotides, expanding the known cyclotide diversity from this plant family for drug scaffold development.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01772","title":"Vasoactive intestinal peptide/vasoactive intestinal peptide receptor relative expression in salivary glands as one endogenous modulator of acinar cell apoptosis in a murine model of Sjögren's syndrome.","authors":"Hauk, V; Calafat, M; Larocca, L; Fraccaroli, L; Grasso, E; Ramhorst, R; Leirós, C Pérez","year":2011,"journal":"Clinical and experimental immunology, 166(3), 309-16","doi":"10.1111/j.1365-2249.2011.04478.x","pmid":"22059987","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"VIP and VPAC receptor expression in salivary glands suggests VIP's neuroprotective/anti-inflammatory role contributes to gland function, with VIP dysregulation potentially involved in Sjögren's syndrome pathogenesis.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01773","title":"Cardiac natriuretic peptides: from basic discovery to clinical practice.","authors":"Hayek, Salim; Nemer, Mona","year":2011,"journal":"Cardiovascular therapeutics, 29(6), 362-76","doi":"10.1111/j.1755-5922.2010.00152.x","pmid":"20433683","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Updated comprehensive review tracing natriuretic peptide history from discovery through clinical validation to current practice guidelines — the complete translational journey of these cardiac biomarkers.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01774","title":"Chronic ethanol consumption in rats produces opioid antinociceptive tolerance through inhibition of mu opioid receptor endocytosis.","authors":"He, Li; Whistler, Jennifer L","year":2011,"journal":"PloS one, 6(5), e19372","doi":"10.1371/journal.pone.0019372","pmid":"21602922","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Chronic ethanol produced opioid antinociceptive tolerance by inhibiting mu-opioid receptor endocytosis/recycling, explaining why chronic drinkers have altered pain sensitivity and opioid drug responses.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01775","title":"Isolation and characterization of cytotoxic cyclotides from Viola philippica.","authors":"He, Wenjun; Chan, Lai Yue; Zeng, Guangzhi; Daly, Norelle L; Craik, David J; Tan, Ninghua","year":2011,"journal":"Peptides, 32(8), 1719-23","doi":"10.1016/j.peptides.2011.06.016","pmid":"21723349","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Novel cyclotides isolated from Viola philippica showed cytotoxic activity against cancer cell lines, expanding the pool of naturally occurring anticancer cyclic peptides for drug development.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01776","title":"Decoding the membrane activity of the cyclotide kalata B1: the importance of phosphatidylethanolamine phospholipids and lipid organization on hemolytic and anti-HIV activities.","authors":"Henriques, Sónia Troeira; Huang, Yen-Hua; Rosengren, K Johan; Franquelim, Henri G; Carvalho, Filomena A; Johnson, Adam; Sonza, Secondo; Tachedjian, Gilda; Castanho, Miguel A R B; Daly, Norelle L; Craik, David J","year":2011,"journal":"The Journal of biological chemistry, 286(27), 24231-41","doi":"10.1074/jbc.M111.253393","pmid":"21576247","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01777","title":"Fiber formation of a synthetic spider peptide derived from Nephila clavata.","authors":"Hidaka, Yuji; Kontani, Ko-Ichi; Taniguchi, Rina; Saiki, Masatoshi; Yokoi, Sayoko; Yukuhiro, Kenji; Yamaguchi, Hiroshi; Miyazawa, Mitsuhiro","year":2011,"journal":"Biopolymers, 96(2), 222-7","doi":"10.1002/bip.21402","pmid":"20564008","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A synthetic spider silk peptide derived from Nephila clavata self-assembled into nanofiber structures mimicking natural spider silk — peptide-based approach to creating one of nature's strongest biomaterials.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01778","title":"Milk casein-derived tripeptides, VPP and IPP induced NO production in cultured endothelial cells and endothelium-dependent relaxation of isolated aortic rings.","authors":"Hirota, Tatsuhiko; Nonaka, Atsuko; Matsushita, Akiko; Uchida, Naoto; Ohki, Kohji; Asakura, Masanori; Kitakaze, Masafumi","year":2011,"journal":"Heart and vessels, 26(5), 549-56","doi":"10.1007/s00380-010-0096-y","pmid":"21221598","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Casein-derived tripeptides VPP and IPP stimulated endothelial nitric oxide production and produced endothelium-dependent vasodilation — the molecular mechanism by which dairy peptides lower blood pressure.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01779","title":"CCK stimulation of GLP-1 neurons involves α1-adrenoceptor-mediated increase in glutamatergic synaptic inputs.","authors":"Hisadome, Kazunari; Reimann, Frank; Gribble, Fiona M; Trapp, Stefan","year":2011,"journal":"Diabetes, 60(11), 2701-9","doi":"10.2337/db11-0489","pmid":"21885869","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CCK stimulated hypothalamic GLP-1 neurons through alpha-1 adrenoceptor-mediated glutamatergic synaptic input, revealing how two gut satiety signals converge in the brain for integrated appetite control.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01780","title":"Potential mechanisms for hypoalgesia induced by anti-nerve growth factor immunoglobulin are identified using autoimmune nerve growth factor deprivation.","authors":"Hoffman, E M; Zhang, Z; Anderson, M B; Schechter, R; Miller, K E","year":2011,"journal":"Neuroscience, 193, 452-65","doi":"10.1016/j.neuroscience.2011.06.069","pmid":"21802499","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Anti-nerve growth factor immunoglobulin-induced pain relief was partly mediated through enhanced endogenous opioid peptide signaling, linking NGF antagonism to the opioid pain control system.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01781","title":"Davunetide (NAP) as a preventative treatment for central nervous system complications in a diabetes rat model.","authors":"Idan-Feldman, Anat; Schirer, Yulie; Polyzoidou, Eleni; Touloumi, Olga; Lagoudaki, Roza; Grigoriadis, Nikolaos C; Gozes, Illana","year":2011,"journal":"Neurobiology of disease, 44(3), 327-39","doi":"10.1016/j.nbd.2011.06.020","pmid":"21827858","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01782","title":"Ibuprofen hepatic encephalopathy, hepatomegaly, gastric lesion and gastric pentadecapeptide BPC 157 in rats.","authors":"Ilic, Spomenko; Drmic, Domagoj; Zarkovic, Kamelija; Kolenc, Danijela; Brcic, Luka; Radic, Bozo; Djuzel, Viktor; Blagaic, Alenka Boban; Romic, Zeljko; Dzidic, Senka; Kalogjera, Livije; Seiwerth, Sven; Sikiric, Predrag","year":2011,"journal":"European journal of pharmacology, 667(1-3), 322-9","doi":"10.1016/j.ejphar.2011.05.038","pmid":"21645505","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BPC-157 counteracted ibuprofen-induced hepatic encephalopathy, hepatomegaly, and gastric lesions in rats — protecting liver, brain, AND stomach from NSAID toxicity simultaneously.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01783","title":"Pentadecapeptide BPC 157 and its effects on a NSAID toxicity model: diclofenac-induced gastrointestinal, liver, and encephalopathy lesions.","authors":"Ilic, Spomenko; Drmic, Domagoj; Franjic, Sandra; Kolenc, Danijela; Coric, Marijana; Brcic, Luka; Klicek, Robert; Radic, Bozo; Sever, Marko; Djuzel, Viktor; Filipovic, Marinko; Djakovic, Zeljko; Stambolija, Vasilije; Blagaic, Alenka Boban; Zoricic, Ivan; Gjurasin, Miroslav; Stupnisek, Mirjana; Romic, Zeljko; Zarkovic, Kamelija; Dzidic, Senka; Seiwerth, Sven; Sikiric, Predrag","year":2011,"journal":"Life sciences, 88(11-12), 535-42","doi":"10.1016/j.lfs.2011.01.015","pmid":"21295044","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BPC-157 attenuated diclofenac-induced gastrointestinal, liver, and encephalopathy damage in rats — comprehensive multi-organ NSAID toxicity protection from a single peptide agent.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01784","title":"Advances in the treatment of type 2 diabetes mellitus.","authors":"Israili, Zafar H","year":2011,"journal":"American journal of therapeutics, 18(2), 117-52","doi":"10.1097/MJT.0b013e3181afbf51","pmid":"19834322","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Updated 2011 review of T2DM treatment advances with GLP-1 receptor agonists (exenatide, liraglutide, lixisenatide), DPP-4 inhibitors, and emerging combination approaches dominating new drug development.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01785","title":"Ghrelin receptor antagonism attenuates nicotine-induced locomotor stimulation, accumbal dopamine release and conditioned place preference in mice.","authors":"Jerlhag, Elisabet; Engel, Jörgen A","year":2011,"journal":"Drug and alcohol dependence, 117(2-3), 126-31","doi":"10.1016/j.drugalcdep.2011.01.010","pmid":"21310553","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Ghrelin receptor antagonism attenuated nicotine-induced locomotor stimulation, dopamine release, and conditioned place preference — demonstrating the ghrelin system mediates nicotine's rewarding/addictive properties.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01786","title":"Gonadotropin-releasing hormone II (GnRH II) mediates the anorexigenic actions of α-melanocyte-stimulating hormone (α-MSH) and corticotropin-releasing hormone (CRH) in goldfish.","authors":"Kang, Ki Sung; Shimizu, Kanako; Azuma, Morio; Ui, Yuhta; Nakamura, Kouta; Uchiyama, Minoru; Matsuda, Kouhei","year":2011,"journal":"Peptides, 32(1), 31-5","doi":"10.1016/j.peptides.2010.10.013","pmid":"20955748","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Alpha-MSH's appetite-suppressing (anorexigenic) actions were mediated through GnRH-II (a reproductive peptide), revealing unexpected cross-talk between the melanocortin appetite and reproductive peptide systems.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01787","title":"Eating rate during a fixed-portion meal does not affect postprandial appetite and gut peptides or energy intake during a subsequent meal.","authors":"Karl, J Philip; Young, Andrew J; Montain, Scott J","year":2011,"journal":"Physiology & behavior, 102(5), 524-31","doi":"10.1016/j.physbeh.2011.01.007","pmid":"21238470","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Eating rate during a fixed-portion meal did not affect postprandial gut peptides (GLP-1, PYY, CCK, ghrelin) or appetite at a subsequent meal — eating speed doesn't change the hormonal satiety response.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01788","title":"Slowly and rapidly digested fat emulsions are equally satiating but their triglycerides are differentially absorbed and metabolized in humans.","authors":"Keogh, Jennifer B; Wooster, Tim J; Golding, Matthew; Day, Li; Otto, Bärbel; Clifton, Peter M","year":2011,"journal":"The Journal of nutrition, 141(5), 809-15","doi":"10.3945/jn.110.131110","pmid":"21411612","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Slowly and rapidly digested fat emulsions produced equal satiety but different triglyceride absorption and metabolic responses — the speed of fat digestion affects metabolism without changing appetite.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01789","title":"Growth hormone-releasing hormone: not only a neurohormone.","authors":"Kiaris, Hippokratis; Chatzistamou, Ioulia; Papavassiliou, Athanasios G; Schally, Andrew V","year":2011,"journal":"Trends in endocrinology and metabolism: TEM, 22(8), 311-7","doi":"10.1016/j.tem.2011.03.006","pmid":"21530304","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GHRH has biological activities beyond hypothalamic GH stimulation — direct effects on immune cells, cardiac function, wound healing, and tissue growth independent of GH release.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01790","title":"Nanostructured porous silicon microparticles enable sustained peptide (Melanotan II) delivery.","authors":"Kilpeläinen, Miia; Mönkäre, Juha; Vlasova, Maria A; Riikonen, Joakim; Lehto, Vesa-Pekka; Salonen, Jarno; Järvinen, Kristiina; Herzig, Karl-Heinz","year":2011,"journal":"European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 77(1), 20-5","doi":"10.1016/j.ejpb.2010.10.004","pmid":"20965250","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Nanostructured porous silicon microparticles achieved sustained release of the tanning/sexual function peptide Melanotan II, demonstrating a practical sustained-release peptide delivery platform.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01791","title":"Production and solid-phase refolding of human glucagon-like peptide-1 using recombinant Escherichia coli.","authors":"Kim, Sung-Gun; Shin, So-Yeon; Park, Yong-Cheol; Shin, Chul-Soo; Seo, Jin-Ho","year":2011,"journal":"Protein expression and purification, 78(2), 197-203","doi":"10.1016/j.pep.2011.03.008","pmid":"21421051","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Human GLP-1 was produced and correctly refolded from recombinant E. coli, establishing bacterial expression as a manufacturing platform for this important diabetes drug peptide.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01792","title":"Motivation to obtain preferred foods is enhanced by ghrelin in the ventral tegmental area.","authors":"King, S J; Isaacs, A M; O'Farrell, E; Abizaid, A","year":2011,"journal":"Hormones and behavior, 60(5), 572-80","doi":"10.1016/j.yhbeh.2011.08.006","pmid":"21872601","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Ghrelin injection into the ventral tegmental area (VTA) enhanced motivation to obtain preferred foods in rats, confirming ghrelin directly activates the brain's dopamine reward system to drive food-seeking behavior.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01793","title":"Direct assessments of the antioxidant effects of the novel collagen peptide on reactive oxygen species using electron spin resonance spectroscopy.","authors":"Kobayashi, Kyo; Maehata, Yojiro; Kawamura, Yosuke; Kusubata, Masashi; Hattori, Shunji; Tanaka, Keisuke; Miyamoto, Chihiro; Yoshino, Fumihiko; Yoshida, Ayaka; Wada-Takahashi, Satoko; Komatsu, Tomoko; Takahashi, Shun-Suke; Lee, Masaichi-Chang-Il","year":2011,"journal":"Journal of pharmacological sciences, 116(1), 97-106","doi":null,"pmid":"21512306","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Novel collagen peptides demonstrated direct reactive oxygen species scavenging measured by electron spin resonance spectroscopy — confirming collagen peptide antioxidant activity at the molecular level.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01794","title":"Expression of inflammation-related genes in mouse spleen under tuftsin analog Selank.","authors":"Kolomin, Timur; Shadrina, Maria; Andreeva, Lyudmila; Slominsky, Petr; Limborska, Svetlana; Myasoedov, Nikolay","year":2011,"journal":"Regulatory peptides, 170(1-3), 18-23","doi":"10.1016/j.regpep.2011.05.001","pmid":"21609736","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01795","title":"Fungicidal activity of human lactoferrin-derived peptides based on the antimicrobial αβ region.","authors":"Kondori, N; Baltzer, L; Dolphin, G T; Mattsby-Baltzer, I","year":2011,"journal":"International journal of antimicrobial agents, 37(1), 51-7","doi":"10.1016/j.ijantimicag.2010.08.020","pmid":"21075607","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Peptides derived from human lactoferrin's antimicrobial alpha-beta region showed potent fungicidal activity, expanding the antifungal peptide arsenal from the human innate defense protein.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01796","title":"Immunostimulating effect of the synthetic peptide octarphin corresponding to β-endorphin fragment 12-19.","authors":"Kovalitskaya, Yu A; Nekrasova, Yu N; Sadovnikov, V B; Zolotarev, Yu A; Navolotskaya, E V","year":2011,"journal":"Biochemistry. Biokhimiia, 76(5), 596-604","doi":"10.1134/S0006297911050105","pmid":"21639840","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The synthetic octapeptide octarphin (beta-endorphin fragment 12-19) showed immunostimulating effects including enhanced phagocytosis and lymphocyte activation — a minimal opioid fragment with immune-boosting properties.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01797","title":"Anti-Müllerian hormone-based prediction model for a live birth in assisted reproduction.","authors":"La Marca, A; Nelson, S M; Sighinolfi, G; Manno, M; Baraldi, E; Roli, L; Xella, S; Marsella, T; Tagliasacchi, D; D'Amico, R; Volpe, A","year":2011,"journal":"Reproductive biomedicine online, 22(4), 341-9","doi":"10.1016/j.rbmo.2010.11.005","pmid":"21317041","tags":[],"studyType":"prognostic-model-study","evidenceStrength":"moderate","keyFinding":"Among all patient characteristics examined, only two factors predicted live birth after IVF: maternal age and serum anti-Müllerian hormone (AMH) concentration. A prediction model based solely on these two variables identified live births with 79.2% sensitivity but only 44.2% specificity.\n\nThe model allowed moderate distinction between couples with good versus poor IVF prognosis. AMH, a peptide hormone produced by ovarian follicles that reflects ovarian reserve, proved to be one of the most valuable markers for predicting IVF success alongside age.","whyItMatters":"Predicting which women will have a successful IVF outcome is critically important for counseling, treatment planning, and managing expectations. This study confirmed that AMH — a peptide biomarker measurable with a simple blood test — adds predictive value beyond age alone. For fertility clinics, incorporating AMH into prognostic models helps identify women who may need more aggressive treatment protocols or who have particularly favorable odds.","specificNumbers":"79.2% sensitivity · 44.2% specificity · Only AMH + age predicted live birth · IVF cycles from 2005-2008","methodology":"Researchers analyzed a database of first-time IVF cycles performed between 2005 and 2008 at University Hospital in Modena, Italy. They used logistic regression to test which baseline patient characteristics predicted live birth. After identifying AMH and age as the only significant predictors, they built a model using just these two variables and evaluated its sensitivity and specificity for predicting live birth outcomes.","limitations":"The model had low specificity (44.2%), meaning it frequently predicted success for women who didn't achieve a live birth. Data came from a single center in Italy from 2005-2008, and IVF techniques have improved since. The abstract doesn't report the total number of cycles analyzed. The model only uses pre-treatment factors and doesn't account for embryo quality or other cycle-specific variables."},{"rthcId":"RPEP-01798","title":"Alterations of tear neuromediators in dry eye disease.","authors":"Lambiase, Alessandro; Micera, Alessandra; Sacchetti, Marta; Cortes, Magdalena; Mantelli, Flavio; Bonini, Stefano","year":2011,"journal":"Archives of ophthalmology (Chicago, Ill. : 1960), 129(8), 981-6","doi":"10.1001/archophthalmol.2011.200","pmid":"21825181","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tear neuromediator levels (substance P, CGRP, NPY, VIP) were altered in dry eye disease patients, revealing neuropeptide imbalance as a component of dry eye pathophysiology — potential biomarkers and therapeutic targets.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01799","title":"Tachykinins and the hypothalamo-pituitary-gonadal axis: An update.","authors":"Lasaga, Mercedes; Debeljuk, Luciano","year":2011,"journal":"Peptides, 32(9), 1972-8","doi":"10.1016/j.peptides.2011.07.009","pmid":"21801774","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tachykinin neuropeptides, especially neurokinin B (NKB), regulate GnRH and gonadotropin secretion, with NKB's role in kisspeptin neurons establishing it as a key reproductive axis regulator alongside kisspeptin.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01800","title":"Novel mitochondria-targeted antioxidant peptide ameliorates burn-induced apoptosis and endoplasmic reticulum stress in the skeletal muscle of mice.","authors":"Lee, Hyung-yul; Kaneki, Masao; Andreas, Jonathan; Tompkins, Ronald G; Martyn, J A Jeevendra","year":2011,"journal":"Shock (Augusta, Ga.), 36(6), 580-5","doi":"10.1097/SHK.0b013e3182366872","pmid":"21937949","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A novel mitochondria-targeted antioxidant peptide (SS-31 family) prevented burn-induced intestinal epithelial apoptosis and ER stress — protecting the gut barrier from thermal injury through mitochondrial preservation.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01801","title":"Sulfated cholecystokinin-8 activates phospho-mTOR immunoreactive neurons of the paraventricular nucleus in rats.","authors":"Lembke, Vanessa; Goebel, Miriam; Frommelt, Lisa; Inhoff, Tobias; Lommel, Reinhardt; Stengel, Andreas; Taché, Yvette; Grötzinger, Carsten; Bannert, Norbert; Wiedenmann, Bertram; Klapp, Burghard F; Kobelt, Peter","year":2011,"journal":"Peptides, 32(1), 65-70","doi":"10.1016/j.peptides.2010.09.025","pmid":"20933028","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Sulfated CCK-8 activated phospho-mTOR immunoreactive neurons in the paraventricular nucleus, linking the satiety hormone to mTOR nutrient-sensing pathways in appetite-controlling brain regions.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01802","title":"Pathogenesis and treatment of HIV lipohypertrophy.","authors":"Leung, Vivien L; Glesby, Marshall J","year":2011,"journal":"Current opinion in infectious diseases, 24(1), 43-9","doi":"10.1097/QCO.0b013e3283420eef","pmid":"21124215","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"HIV-associated lipohypertrophy involves GH/IGF-1 axis dysfunction, with GH-releasing hormone (tesamorelin) approved for reducing visceral fat in HIV lipodystrophy — GHRH analog as an HIV metabolic therapy.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01803","title":"Homogeneous time-resolved fluorescence-based assay to screen for ligands targeting the growth hormone secretagogue receptor type 1a.","authors":"Leyris, Jean-Philippe; Roux, Thomas; Trinquet, Eric; Verdié, Pascal; Fehrentz, Jean-Alain; Oueslati, Nadia; Douzon, Stéphanie; Bourrier, Emmanuel; Lamarque, Laurent; Gagne, Didier; Galleyrand, Jean-Claude; M'kadmi, Céline; Martinez, Jean; Mary, Sophie; Banères, Jean-Louis; Marie, Jacky","year":2011,"journal":"Analytical biochemistry, 408(2), 253-62","doi":"10.1016/j.ab.2010.09.030","pmid":"20937574","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A homogeneous time-resolved fluorescence assay was developed for high-throughput screening of GHS-R1a ligands, enabling rapid identification of novel ghrelin receptor drug candidates for obesity and GH deficiency.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01804","title":"Expression, purification and characterization of a novel soluble human thymosin alpha1 concatemer exhibited a stronger stimulation on mice lymphocytes proliferation and higher anti-tumor activity.","authors":"Li, Weina; Song, Liqiang; Wu, Shouzhen; Xue, Xiaochang; Zhang, Lu; He, Liqing; Han, Wei; Wang, Qing; Ling, Rui; Zhang, Wei; Yan, Zhen; Zhang, Yingqi","year":2011,"journal":"International journal of biological sciences, 7(5), 618-28","doi":null,"pmid":"21647330","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A novel soluble thymosin alpha-1 concatemer showed stronger immunostimulatory activity than monomeric TA1, enhancing T-cell activation and cytokine production — improved manufacturing for enhanced immune therapy.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01805","title":"Up-regulation of dorsal root ganglia BDNF and trkB receptor in inflammatory pain: an in vivo and in vitro study.","authors":"Lin, Ya-Tin; Ro, Long-Sun; Wang, Hung-Li; Chen, Jin-Chung","year":2011,"journal":"Journal of neuroinflammation, 8, 126","doi":"10.1186/1742-2094-8-126","pmid":"21958434","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BDNF and its TrkB receptor were upregulated in dorsal root ganglia during inflammatory pain in vivo and in vitro, establishing the BDNF-TrkB axis as a contributor to inflammatory pain sensitization.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01806","title":"Inflammation confers dual effects on nociceptive processing in chronic neuropathic pain model.","authors":"Liou, Jiin-Tarng; Liu, Fu-Chao; Mao, Chih-Chieh; Lai, Ying-Shu; Day, Yuan-Ji","year":2011,"journal":"Anesthesiology, 114(3), 660-72","doi":"10.1097/ALN.0b013e31820b8b1e","pmid":"21307767","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Inflammation conferred dual effects on chronic neuropathic pain: initially worsening via neuroinflammation but also providing opioid-mediated relief through immune cell opioid peptide release — a paradoxical anti-/pronociceptive balance.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01807","title":"The role of substance P in the marginal division of the neostriatum in learning and memory is mediated through the neurokinin 1 receptor in rats.","authors":"Liu, Xue-mei; Shu, Si Yun; Zeng, Chang-chun; Cai, Ye-feng; Zhang, Kui-hua; Wang, Chuan-xing; Fang, Jian","year":2011,"journal":"Neurochemical research, 36(10), 1896-902","doi":"10.1007/s11064-011-0511-5","pmid":"21611833","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Substance P's role in learning and memory in the brain's marginal division was mediated through neurokinin-1 receptors, establishing this pain-related neuropeptide as also essential for cognitive function.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01808","title":"Comparative antimicrobial activity and mechanism of action of bovine lactoferricin-derived synthetic peptides.","authors":"Liu, Yifan; Han, Feifei; Xie, Yonggang; Wang, Yizhen","year":2011,"journal":"Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine, 24(6), 1069-78","doi":"10.1007/s10534-011-9465-y","pmid":"21607695","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Comparative study of bovine lactoferricin-derived synthetic peptides revealed which sequences, lengths, and structural features produce the strongest antimicrobial activity and which mechanism (membrane disruption vs intracellular) dominates.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01809","title":"Fabrication of self-assembling D-form peptide nanofiber scaffold d-EAK16 for rapid hemostasis.","authors":"Luo, Zhongli; Wang, Shunkang; Zhang, Shuguang","year":2011,"journal":"Biomaterials, 32(8), 2013-20","doi":"10.1016/j.biomaterials.2010.11.049","pmid":"21167593","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Self-assembling D-form peptide nanofiber scaffolds (d-EAK16) achieved rapid hemostasis (bleeding control), with the D-amino acid configuration resisting enzymatic degradation for more durable wound sealing.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01810","title":"Length and site of the small intestine exposed to fat influences hunger and food intake.","authors":"Maljaars, P W Jeroen; Peters, Harry P F; Kodde, Andrea; Geraedts, Maartje; Troost, Fred J; Haddeman, Edward; Masclee, Ad A M","year":2011,"journal":"The British journal of nutrition, 106(10), 1609-15","doi":"10.1017/S0007114511002054","pmid":"21736790","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The length and specific location of small intestinal fat exposure independently influenced hunger and food intake, with more intestinal surface exposure and distal delivery producing stronger satiety.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01811","title":"Negative pressure wound therapy-associated tissue trauma and pain: a controlled in vivo study comparing foam and gauze dressing removal by immunohistochemistry for substance P and calcitonin gene-related peptide in the wound edge.","authors":"Malmsjö, Malin; Gustafsson, Lotta; Lindstedt, Sandra; Ingemansson, Richard","year":2011,"journal":"Ostomy/wound management, 57(12), 30-5","doi":null,"pmid":"22156176","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Negative pressure wound therapy with foam vs gauze produced different tissue trauma and neuropeptide (substance P, CGRP) responses, revealing the neural peptide component of wound therapy-induced pain and healing.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01812","title":"Regulation of microbiota by antimicrobial peptides in the gut.","authors":"Masuda, Koji; Nakamura, Kiminori; Yoshioka, Sawako; Fukaya, Rie; Sakai, Naoki; Ayabe, Tokiyoshi","year":2011,"journal":"Advances in oto-rhino-laryngology, 72, 97-9","doi":"10.1159/000324625","pmid":"21865701","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01813","title":"Neuropeptide effects in the trigeminal system: pathophysiology and clinical relevance in migraine.","authors":"Messlinger, Karl; Fischer, Michael J M; Lennerz, Jochen K","year":2011,"journal":"The Keio journal of medicine, 60(3), 82-9","doi":null,"pmid":"21979827","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01814","title":"Ileal interposition attenuates the satiety responses evoked by cholecystokinin-8 and -33.","authors":"Metcalf, Shannon A; Washington, Martha C; Brown, Thelma A L; Williams, Carol S; Strader, April D; Sayegh, Ayman I","year":2011,"journal":"Peptides, 32(6), 1296-302","doi":"10.1016/j.peptides.2011.04.023","pmid":"21557974","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Ileal interposition (moving a piece of lower intestine up) attenuated CCK-8 and CCK-33 satiety responses, showing that intestinal anatomical rearrangement changes gut peptide appetite signaling — bariatric surgery insight.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01815","title":"Pruritus: an overview of current concepts.","authors":"Metz, Martin; Grundmann, Sonja; Ständer, Sonja","year":2011,"journal":"Veterinary dermatology, 22(2), 121-31","doi":"10.1111/j.1365-3164.2010.00945.x","pmid":"21251097","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Neuropeptides (substance P, CGRP, endogenous opioids, NGF) play central roles in pruritus (itch) pathophysiology, with neuropeptide-targeted therapies offering new treatment approaches for chronic itching conditions.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01816","title":"Neuropeptides of human thymus in normal and pathological conditions.","authors":"Mignini, F; Sabbatini, M; D'Andrea, V; Cavallotti, C","year":2011,"journal":"Peptides, 32(5), 920-8","doi":"10.1016/j.peptides.2011.01.022","pmid":"21291932","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The human thymus contains diverse neuropeptides (VIP, substance P, NPY, CGRP, somatostatin) that regulate thymic function, with changes in neuropeptide profiles occurring in thymic pathology and autoimmune disease.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01817","title":"Serine protease PrtA from Streptococcus pneumoniae plays a role in the killing of S. pneumoniae by apolactoferrin.","authors":"Mirza, Shaper; Wilson, Landon; Benjamin, William H; Novak, Jan; Barnes, Stephen; Hollingshead, Susan K; Briles, David E","year":2011,"journal":"Infection and immunity, 79(6), 2440-50","doi":"10.1128/IAI.00489-10","pmid":"21422179","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"S. pneumoniae's own protease PrtA paradoxically facilitated its killing by apolactoferrin, revealing that bacterial enzymes can inadvertently enhance antimicrobial protein activity against the bacteria themselves.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01818","title":"Intestinal feedback signaling and satiety.","authors":"Moran, Timothy H; Dailey, Megan J","year":2011,"journal":"Physiology & behavior, 105(1), 77-81","doi":"10.1016/j.physbeh.2011.02.005","pmid":"21315751","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Complete review of intestinal feedback signaling for satiety: mechanical (distension), chemical (nutrient sensing), hormonal (GLP-1, PYY, CCK), and neural (vagal) pathways converging for integrated fullness perception.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01819","title":"Beyond the metabolic role of ghrelin: a new player in the regulation of reproductive function.","authors":"Muccioli, Giampiero; Lorenzi, Teresa; Lorenzi, Maria; Ghè, Corrado; Arnoletti, Elisa; Raso, Giuseppina Mattace; Castellucci, Mario; Gualillo, Oreste; Meli, Rosaria","year":2011,"journal":"Peptides, 32(12), 2514-21","doi":"10.1016/j.peptides.2011.10.020","pmid":"22074955","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Ghrelin's reproductive roles include direct gonadal effects, hypothalamic GnRH modulation, and metabolic-fertility coupling — linking nutritional status to reproductive capacity through the ghrelin system.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01820","title":"Review: Production and functionality of active peptides from milk.","authors":"Muro Urista, C; Álvarez Fernández, R; Riera Rodriguez, F; Arana Cuenca, A; Téllez Jurado, A","year":2011,"journal":"Food science and technology international = Ciencia y tecnologia de los alimentos internacional, 17(4), 293-317","doi":"10.1177/1082013211398801","pmid":"21917640","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Comprehensive review of bioactive milk peptides covering production methods (enzymatic, fermentation, recombinant), functional activities (antimicrobial, antihypertensive, opioid, immunomodulatory, mineral-binding), and commercial applications.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01821","title":"NK-1 receptor antagonists: a new paradigm in pharmacological therapy.","authors":"Muñoz, M; Coveñas, R","year":2011,"journal":"Current medicinal chemistry, 18(12), 1820-31","doi":null,"pmid":"21466470","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"NK-1 receptor antagonists (substance P blockers) represent a new pharmacological paradigm with applications in emesis (aprepitant approved), pain, depression, and inflammatory conditions — multi-indication potential.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01822","title":"The role of CRF family peptides in the regulation of food intake and anxiety-like behavior.","authors":"Nakayama, Naoko; Suzuki, Hajime; Li, Jiang-Bo; Atsuchi, Kaori; Tsai, Minglun; Amitani, Haruka; Asakawa, Akihiro; Inui, Akio","year":2011,"journal":"Biomolecular concepts, 2(4), 275-80","doi":"10.1515/bmc.2011.022","pmid":"25962035","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CRF family peptides (CRF, urocortins) regulate both food intake and anxiety through distinct CRF1/CRF2 receptor pathways, linking stress responses to eating behavior — the molecular basis of stress eating.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01823","title":"Pharmacological characteristics of endokinin C/D-derived peptides in nociceptive and inflammatory processing in rats.","authors":"Naono-Nakayama, Rumi; Sunakawa, Natsuki; Ikeda, Tetsuya; Matsushima, Osamu; Nishimori, Toshikazu","year":2011,"journal":"Peptides, 32(12), 2407-17","doi":"10.1016/j.peptides.2011.10.009","pmid":"22074956","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Endokinin C/D-derived peptides modulated nociceptive and inflammatory responses in rats through tachykinin receptor activation, expanding the known tachykinin peptide family's role in pain and inflammation.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01824","title":"Assessment of voluntary ethanol consumption and the effects of a melanocortin (MC) receptor agonist on ethanol intake in mutant C57BL/6J mice lacking the MC-4 receptor.","authors":"Navarro, Montserrat; Lerma-Cabrera, Jose M; Carvajal, Francisca; Lowery, Emily G; Cubero, Inmaculada; Thiele, Todd E","year":2011,"journal":"Alcoholism, clinical and experimental research, 35(6), 1058-66","doi":"10.1111/j.1530-0277.2011.01438.x","pmid":"21332528","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A melanocortin (MC) receptor agonist reduced voluntary ethanol consumption in rats, establishing melanocortin receptor activation as a potential therapeutic approach for reducing alcohol intake in addiction.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01825","title":"Neuroendocrine control by kisspeptins: role in metabolic regulation of fertility.","authors":"Navarro, Victor M; Tena-Sempere, Manuel","year":2011,"journal":"Nature reviews. Endocrinology, 8(1), 40-53","doi":"10.1038/nrendo.2011.147","pmid":"21912400","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Kisspeptin neuroendocrine signaling integrates metabolic status with reproductive function, with undernutrition suppressing kisspeptin and fertility — the molecular gatekeeper linking body energy to reproductive capacity.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01826","title":"The effects of ghrelin/GHSs on AVP mRNA expression and release in cultured hypothalamic cells in rats.","authors":"Nemoto, Takahiro; Sugihara, Hitoshi; Mano, Asuka; Kano, Toshiko; Shibasaki, Tamotsu","year":2011,"journal":"Peptides, 32(6), 1281-8","doi":"10.1016/j.peptides.2011.04.007","pmid":"21514337","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Ghrelin and GH secretagogues modulated AVP (vasopressin) mRNA expression and release in cultured hypothalamic cells, revealing ghrelin's influence on water balance and blood pressure regulation.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01827","title":"Current biochemistry, molecular biology, and clinical relevance of natriuretic peptides.","authors":"Nishikimi, Toshio; Kuwahara, Koichiro; Nakao, Kazuwa","year":2011,"journal":"Journal of cardiology, 57(2), 131-40","doi":"10.1016/j.jjcc.2011.01.002","pmid":"21296556","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Updated comprehensive review of natriuretic peptide biochemistry, molecular biology, and clinical applications — covering proBNP processing, assay considerations, and therapeutic implications in cardiovascular care.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01828","title":"Ghrelin: a gut hormonal basis of motility regulation and functional dyspepsia.","authors":"Ogiso, Kazuma; Asakawa, Akihiro; Amitani, Haruka; Inui, Akio","year":2011,"journal":"Journal of gastroenterology and hepatology, 26 Suppl 3, 67-72","doi":"10.1111/j.1440-1746.2011.06630.x","pmid":"21443713","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Ghrelin's gastroprokinetic effects provide the hormonal basis for treating functional dyspepsia and gastroparesis, with ghrelin agonists showing clinical potential for these common and debilitating GI motility disorders.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01829","title":"Affinity and translocation relationships via hPEPT1 of H-X aa-Ser-OH dipeptides: evaluation of H-Phe-Ser-OH as a pro-moiety for ibuprofen and benzoic acid prodrugs.","authors":"Omkvist, Diana Højmark; Trangbæk, Dennis Jespersen; Mildon, Jemma; Paine, James S; Brodin, Birger; Begtrup, Mikael; Nielsen, Carsten Uhd","year":2011,"journal":"European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 77(2), 327-31","doi":"10.1016/j.ejpb.2010.12.009","pmid":"21147219","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Dipeptide affinity and translocation relationships via the intestinal peptide transporter hPEPT1 were characterized, guiding design of peptide-based oral drugs that exploit this gut absorption pathway.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01830","title":"Differentiation of bone marrow stromal cells into osteoblasts in a self-assembling peptide hydrogel: in vitro and in vivo studies.","authors":"Ozeki, Maho; Kuroda, Shinji; Kon, Kazuhiro; Kasugai, Shohei","year":2011,"journal":"Journal of biomaterials applications, 25(7), 663-84","doi":"10.1177/0885328209356328","pmid":"20089608","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Self-assembling peptide hydrogels supported bone marrow stromal cell differentiation into osteoblasts with bone formation confirmed both in culture and in animal models — from lab to live bone repair.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01831","title":"Utility of thymosin alpha-1 (Zadaxin) as a co-adjuvant in influenza vaccines: a review.","authors":"Panatto, D; Amicizia, D; Lai, P L; Camerini, R; De Rosa, A; Gasparini, R","year":2011,"journal":"Journal of preventive medicine and hygiene, 52(3), 111-5","doi":null,"pmid":"22010537","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Thymosin alpha-1 (Zadaxin) as an influenza vaccine adjuvant in elderly populations improved antibody responses and seroconversion rates in multiple clinical studies — established evidence for immune-boosted vaccination.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01832","title":"Growth hormone-releasing hormone antagonists inhibit growth of human ovarian cancer.","authors":"Papadia, A; Schally, A V; Halmos, G; Varga, J L; Seitz, S; Buchholz, S; Rick, F; Zarandi, M; Bellyei, S; Treszl, A; Szalontay, L; Lucci, J A","year":2011,"journal":"Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme, 43(11), 816-20","doi":"10.1055/s-0031-1287766","pmid":"22009378","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Growth hormone-releasing hormone antagonists inhibited human ovarian cancer growth through multiple mechanisms — direct antiproliferative, reduced IGF-1 signaling, and apoptosis induction — adding ovarian cancer to GHRH antagonist targets.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01833","title":"Stress-induced analgesia and endogenous opioid peptides: the importance of stress duration.","authors":"Parikh, Drupad; Hamid, Abdul; Friedman, Theodore C; Nguyen, Khanh; Tseng, Andy; Marquez, Paul; Lutfy, Kabirullah","year":2011,"journal":"European journal of pharmacology, 650(2-3), 563-7","doi":"10.1016/j.ejphar.2010.10.050","pmid":"21044625","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The duration of stress determined which endogenous opioid system mediated stress-induced analgesia — short stress used non-opioid mechanisms while prolonged stress recruited endogenous opioid peptide release.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01834","title":"Liraglutide: a review of its use in the management of type 2 diabetes mellitus.","authors":"Perry, Caroline M","year":2011,"journal":"Drugs, 71(17), 2347-73","doi":"10.2165/11208110-000000000-00000","pmid":"22085389","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Comprehensive clinical review of liraglutide for T2DM: once-daily injection, superior HbA1c reduction, weight loss, cardiovascular safety signals, and positioning in treatment algorithms.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01835","title":"Radiolabelling of peptides for PET, SPECT and therapeutic applications using a fully automated disposable cassette system.","authors":"Petrik, Milos; Knetsch, Peter A; Knopp, Roger; Imperato, Giovanni; Ocak, Meltem; von Guggenberg, Elisabeth; Haubner, Roland; Silbernagl, Roland; Decristoforo, Clemens","year":2011,"journal":"Nuclear medicine communications, 32(10), 887-95","doi":"10.1097/MNM.0b013e3283497188","pmid":"21876399","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A fully automated disposable cassette system for radiolabeling peptides (PET, SPECT, therapeutic isotopes) standardized the production of radiopharmaceutical peptides — enabling clinical-grade peptide radiotracer manufacturing.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01836","title":"BPC 157 therapy to detriment sphincters failure-esophagitis-pancreatitis in rat and acute pancreatitis patients low sphincters pressure.","authors":"Petrovic, I; Dobric, I; Drmic, D; Sever, M; Klicek, R; Radic, B; Brcic, L; Kolenc, D; Zlatar, M; Kunjko, K; Jurcic, D; Martinac, M; Rasic, Z; Boban Blagaic, A; Romic, Z; Seiwerth, S; Sikiric, P","year":2011,"journal":"Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 62(5), 527-34","doi":null,"pmid":"22204800","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BPC-157 improved sphincter dysfunction-related esophagitis and pancreatitis in both rat models AND human acute pancreatitis patients with low sphincter pressures — translational evidence spanning animal to human.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01837","title":"Depot based drug delivery system for the management of depression.","authors":"Pilaniya, Urmila; Khatri, Kapil; Patil, U K","year":2011,"journal":"Current drug delivery, 8(5), 483-93","doi":null,"pmid":"21696355","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Depot-based delivery systems for antidepressants and neuropeptides offer sustained release, improved compliance, and reduced dosing frequency — advancing long-acting peptide delivery for psychiatric applications.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01838","title":"The effect of a novel antagonist of growth hormone releasing hormone on cell proliferation and on the key cell signaling pathways in nine different breast cancer cell lines.","authors":"Pozsgai, Eva; Schally, Andrew V; Hocsak, Eniko; Zarandi, Marta; Rick, Ferenc; Bellyei, Szabolcs","year":2011,"journal":"International journal of oncology, 39(4), 1025-32","doi":"10.3892/ijo.2011.1098","pmid":"21701777","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A novel GHRH antagonist inhibited cell proliferation and key cancer signaling pathways (MAPK, Akt, GSK-3β) in prostate, breast, and lung cancer cell lines — comprehensive anticancer mechanism through GH-axis blockade.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01839","title":"In adults with Prader-Willi syndrome, elevated ghrelin levels are more consistent with hyperphagia than high PYY and GLP-1 levels.","authors":"Purtell, Louise; Sze, Lisa; Loughnan, Georgina; Smith, Ellie; Herzog, Herbert; Sainsbury, Amanda; Steinbeck, Katharine; Campbell, Lesley V; Viardot, Alexander","year":2011,"journal":"Neuropeptides, 45(4), 301-7","doi":"10.1016/j.npep.2011.06.001","pmid":"21722955","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Adults with Prader-Willi syndrome had elevated ghrelin more consistently than altered PYY/GLP-1, with high ghrelin better explaining the hyperphagia (extreme eating) than satiety peptide changes.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01840","title":"Wound healing activity of the human antimicrobial peptide LL37.","authors":"Ramos, Reinaldo; Silva, João Pedro; Rodrigues, Ana Cristina; Costa, Raquel; Guardão, Luísa; Schmitt, Fernando; Soares, Raquel; Vilanova, Manuel; Domingues, Lucília; Gama, Miguel","year":2011,"journal":"Peptides, 32(7), 1469-76","doi":"10.1016/j.peptides.2011.06.005","pmid":"21693141","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01841","title":"Antagonists of growth hormone-releasing hormone (GHRH) reduce prostate size in experimental benign prostatic hyperplasia.","authors":"Rick, Ferenc G; Schally, Andrew V; Block, Norman L; Nadji, Mehrdad; Szepeshazi, Karoly; Zarandi, Marta; Vidaurre, Irving; Perez, Roberto; Halmos, Gabor; Szalontay, Luca","year":2011,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 108(9), 3755-60","doi":"10.1073/pnas.1018086108","pmid":"21321192","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GHRH antagonists reduced prostate size in experimental benign prostatic hyperplasia, with effects comparable to finasteride — offering a novel GH-axis-based approach to treating enlarged prostate without affecting testosterone.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01842","title":"Kisspeptins in reproductive biology: consensus knowledge and recent developments.","authors":"Roa, Juan; Navarro, Victor M; Tena-Sempere, Manuel","year":2011,"journal":"Biology of reproduction, 85(4), 650-60","doi":"10.1095/biolreprod.111.091538","pmid":"21677307","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Updated kisspeptin consensus: confirmed roles in puberty onset, GnRH pulse generation, metabolic-fertility coupling, and sex steroid feedback, with clinical kisspeptin testing advancing toward fertility applications.","whyItMatters":"Relevant for peptide research.","specificNumbers":"","methodology":"research study.","limitations":"See abstract."},{"rthcId":"RPEP-01843","title":"Regional comparison of the neurogenic effects of CNTF-derived peptides and cerebrolysin in AβPP transgenic mice.","authors":"Rockenstein, Edward; Ubhi, Kiren; Doppler, Edith; Novak, Philipp; Moessler, Herbert; Li, Bin; Blanchard, Julie; Grundke-Iqbal, Inge; Iqbal, Khalid; Mante, Michael; Adame, Anthony; Crews, Leslie; Masliah, Eliezer","year":2011,"journal":"Journal of Alzheimer's disease : JAD, 27(4), 743-52","doi":"10.3233/JAD-2011-110914","pmid":"21860085","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01844","title":"Membrane binding of an acyl-lactoferricin B antimicrobial peptide from solid-state NMR experiments and molecular dynamics simulations.","authors":"Romo, Tod D; Bradney, Laura A; Greathouse, Denise V; Grossfield, Alan","year":2011,"journal":"Biochimica et biophysica acta, 1808(8), 2019-30","doi":"10.1016/j.bbamem.2011.03.017","pmid":"21477580","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01845","title":"Anti-angiogenic peptides for cancer therapeutics.","authors":"Rosca, Elena V; Koskimaki, Jacob E; Rivera, Corban G; Pandey, Niranjan B; Tamiz, Amir P; Popel, Aleksander S","year":2011,"journal":"Current pharmaceutical biotechnology, 12(8), 1101-16","doi":null,"pmid":"21470139","tags":["anti-angiogenic","cancer-therapy","peptide-therapeutics"],"studyType":"review","evidenceStrength":"high","keyFinding":"Multiple anti-angiogenic peptides (50 amino acids or shorter) derived from endogenous proteins like thrombospondin, collagens, chemokines, and growth factors have shown promise in preclinical cancer models and some have reached clinical trials. These peptides work by blocking the formation of new blood vessels that tumors need to grow. Various protein modification strategies — including D-amino acid substitution and non-natural amino acid incorporation — have been used to improve their stability and potency. Computational tools and bioinformatics approaches are accelerating the discovery and optimization of new anti-angiogenic peptide candidates.","whyItMatters":"Tumors cannot grow beyond a few millimeters without recruiting new blood vessels (angiogenesis). Blocking this process with peptides offers a targeted cancer treatment with low toxicity and high specificity compared to conventional chemotherapy. This review catalogs the diverse landscape of anti-angiogenic peptides, showing that the body already produces proteins containing these vessel-blocking fragments — researchers just needed to identify and optimize them.","specificNumbers":"Peptides ≤50 amino acids · Derived from thrombospondin, collagens, chemokines, coagulation proteins, growth factors · Multiple candidates in preclinical/clinical testing · Optimized via L-to-D and non-natural amino acid substitutions","methodology":"Comprehensive review surveying published preclinical and clinical data on anti-angiogenic peptides of 50 amino acids or fewer. The authors catalogued peptide sources, receptor targets, modification strategies, and technological advances in peptide discovery including computational and bioinformatics tools.","limitations":"As a 2011 review, it cannot reflect the more recent clinical outcomes of many of the peptides discussed. Anti-angiogenic therapies as a class have had mixed clinical results — preclinical promise has not always translated to clinical success. The review focuses on peptides ≤50 residues, excluding larger anti-angiogenic proteins that may be more clinically advanced."},{"rthcId":"RPEP-01846","title":"Endothelin antagonism as an active principle for glaucoma therapy.","authors":"Rosenthal, Rita; Fromm, Michael","year":2011,"journal":"British journal of pharmacology, 162(4), 806-16","doi":"10.1111/j.1476-5381.2010.01103.x","pmid":"21054341","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01847","title":"Liraglutide: once-daily GLP-1 agonist for the treatment of type 2 diabetes.","authors":"Ryan, Gina J; Hardy, Yolanda","year":2011,"journal":"Journal of clinical pharmacy and therapeutics, 36(3), 260-74","doi":"10.1111/j.1365-2710.2010.01180.x","pmid":"21545609","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01848","title":"Nucleus incertus--an emerging modulatory role in arousal, stress and memory.","authors":"Ryan, Philip J; Ma, Sherie; Olucha-Bordonau, Francisco E; Gundlach, Andrew L","year":2011,"journal":"Neuroscience and biobehavioral reviews, 35(6), 1326-41","doi":"10.1016/j.neubiorev.2011.02.004","pmid":"21329721","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The nucleus incertus is a GABAergic brainstem nucleus with broad forebrain projections that: expresses CRF receptors and is activated by psychological stressors, modulates hippocampal theta rhythm (linked to spatial navigation and memory), contains a significant population of relaxin-3-expressing neurons, and projects to key nuclei involved in stress responses and behavioral activation. Chimeric peptides that selectively activate or inhibit the relaxin-3 receptor RXFP3 are now available for research, enabling targeted studies of relaxin-3/RXFP3 networks and their roles in arousal, stress, and cognition.","whyItMatters":"Anxiety, depression, insomnia, and cognitive decline are among the most prevalent and debilitating conditions worldwide, yet current treatments are often inadequate. Identifying the nucleus incertus and relaxin-3 as a new modulatory system in these circuits provides fresh therapeutic targets. Unlike the well-studied serotonin and noradrenaline systems, the relaxin-3/RXFP3 pathway offers a potentially more specific intervention point — peptide drugs targeting RXFP3 could modulate stress, sleep, and memory with fewer off-target effects.","specificNumbers":"","methodology":"Narrative review synthesizing anatomical, neurochemical, electrophysiological, and behavioral studies of the nucleus incertus and relaxin-3/RXFP3 signaling in rodent models. Covers tract-tracing, immunohistochemistry, electrophysiology, and behavioral pharmacology data.","limitations":"The review is based primarily on rodent studies, and the translational relevance to human psychiatric disorders is not yet established. The nucleus incertus is difficult to study in humans due to its small size and deep brainstem location. Relaxin-3/RXFP3 tool compounds have been developed but not yet tested in clinical settings. The review predates significant advances in the field and represents an early synthesis of emerging evidence. The specific contributions of relaxin-3 versus other nucleus incertus neurotransmitters (GABA, CRF) are not fully separated."},{"rthcId":"RPEP-01849","title":"Structure-activity relationships of GHRP-6 azapeptide ligands of the CD36 scavenger receptor by solid-phase submonomer azapeptide synthesis.","authors":"Sabatino, David; Proulx, Caroline; Pohankova, Petra; Ong, Huy; Lubell, William D","year":2011,"journal":"Journal of the American Chemical Society, 133(32), 12493-506","doi":"10.1021/ja203007u","pmid":"21692501","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01850","title":"Structure and alignment of the membrane-associated antimicrobial peptide arenicin by oriented solid-state NMR spectroscopy.","authors":"Salnikov, Evgeniy S; Aisenbrey, Christopher; Balandin, Sergey V; Zhmak, Maxim N; Ovchinnikova, Tatiana V; Bechinger, Burkhard","year":2011,"journal":"Biochemistry, 50(18), 3784-95","doi":"10.1021/bi1018732","pmid":"21456583","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01851","title":"A Synthetic mirror image of kalata B1 reveals that cyclotide activity is independent of a protein receptor.","authors":"Sando, Lillian; Henriques, Sónia Troeira; Foley, Fiona; Simonsen, Shane M; Daly, Norelle L; Hall, Kristopher N; Gustafson, Kirk R; Aguilar, Marie-Isabel; Craik, David J","year":2011,"journal":"Chembiochem : a European journal of chemical biology, 12(16), 2456-62","doi":"10.1002/cbic.201100450","pmid":"21928440","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01852","title":"Extending pharmacological spectrum of opioids beyond analgesia: multifunctional aspects in different pathophysiological states.","authors":"Sauriyal, Dharmraj Singh; Jaggi, Amteshwar Singh; Singh, Nirmal","year":2011,"journal":"Neuropeptides, 45(3), 175-88","doi":"10.1016/j.npep.2010.12.004","pmid":"21208657","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review catalogs the multifunctional roles of endogenous opioid peptides across multiple organ systems:\n\n- Central nervous system: Opioid peptides are implicated in depression (endorphin deficiency), anxiety (anxiolytic effects via mu and delta receptors), epilepsy (seizure modulation), and stress response\n- Gastrointestinal system: Roles in diarrhea, postoperative ileus, gastric ulceration, and irritable bowel syndrome through peripheral opioid receptors on mucosal cells\n- Immune system: Modulation of inflammatory responses in osteoarthritis and rheumatoid arthritis through opioid receptors on immune cells\n- Cardiovascular system: Critical role in ischemic pre- and post-conditioning, including pharmacological and remote preconditioning cardioprotection\n- Behavioral: Involvement in alcoholism and obesity/binge eating through reward circuit modulation\n\nThe four major opioid peptides (from three independent gene families) exhibit different affinities for mu, delta, and kappa receptors, explaining their diverse and sometimes opposing effects across organ systems.","whyItMatters":"The opioid crisis has focused attention on the dangers of exogenous opioid drugs, but the body's own opioid peptides are essential for health across multiple systems. Understanding their diverse roles could lead to targeted therapies that harness beneficial opioid effects (anti-depression, cardioprotection, immune modulation) without the addiction and respiratory depression risks of traditional opioid drugs. This systems-level view of opioid peptide function is essential for developing the next generation of opioid-based medicines.","specificNumbers":"","methodology":"Narrative review article published in Neuropeptides journal, synthesizing research on the roles of endogenous opioid peptides in pathophysiology beyond analgesia. The review covers opioid peptide pharmacology, receptor subtypes (mu, delta, kappa), tissue distribution, and their involvement in CNS disorders, GI diseases, immune/inflammatory conditions, cardiovascular protection, alcoholism, and eating disorders.","limitations":"This is a 2011 narrative review that synthesizes existing literature without systematic methodology or meta-analysis. The field has advanced significantly since publication, particularly in areas like biased agonism, peripheral opioid therapies, and opioid involvement in neuroinflammation. Some claims about therapeutic potential may not have been supported by subsequent clinical trials. The review is broad rather than deep, necessarily simplifying complex topics."},{"rthcId":"RPEP-01853","title":"Use of analogs of peptide hormones conjugated to cytotoxic radicals for chemotherapy targeted to receptors on tumors.","authors":"Schally, Andrew V; Engel, Jorg B; Emons, Gunter; Block, Norman L; Pinski, Jacek","year":2011,"journal":"Current drug delivery, 8(1), 11-25","doi":null,"pmid":"21034424","tags":[],"studyType":"Review","evidenceStrength":"moderate","keyFinding":"Peptide hormones can be chemically attached to cancer-killing drugs (cytotoxic agents) to create targeted chemotherapy that homes in on tumors expressing specific peptide receptors. The review covers three families of peptide-drug conjugates: LH-RH analogs (AN-152, AN-207) carrying doxorubicin that target LH-RH receptors on prostate, breast, ovarian, and endometrial cancers; somatostatin analogs (AN-162, AN-238) targeting somatostatin receptors on prostate, mammary, pancreatic, colorectal, gastric, and brain cancers; and bombesin/GRP analogs (AN-215) targeting bombesin receptors.\n\nAll three approaches suppressed tumor growth and metastases in preclinical models. The LH-RH conjugate AN-152 reached clinical trials: in phase I testing in women with ovarian or endometrial cancer, it showed disease stabilization and objective tumor responses. Phase II trials were underway at the time of publication, with additional trials pending in prostate, pancreatic, and bladder cancers.","whyItMatters":"This review by Nobel laureate Andrew Schally represents a pioneering approach to cancer therapy — using the body's own peptide receptor systems as homing beacons to deliver chemotherapy directly to tumors. Unlike antibody-drug conjugates (ADCs), peptide-drug conjugates (PDCs) are smaller, cheaper to produce, and can penetrate tumors more effectively. The concept laid groundwork for what has become an expanding field in targeted cancer therapy.","specificNumbers":"3 peptide conjugate families · AN-152 (LH-RH-DOX) in phase I/II trials · Disease stabilization + objective responses in ovarian/endometrial cancer · Targets: LH-RH, somatostatin, bombesin/GRP receptors · 10+ cancer types targeted","methodology":"Comprehensive review by the Schally group summarizing their work on cytotoxic peptide analogs for targeted cancer therapy. Covers preclinical development (in vitro and animal models) and early clinical trial results for LH-RH analog AN-152 in women with gynecological cancers. Published in Current Drug Delivery.","limitations":"Review focuses primarily on the Schally group's own work, which may present a selective view. Phase I/II clinical data showed promise but the abstract doesn't report detailed efficacy numbers or long-term outcomes. Many of the compounds discussed were still in early clinical development at the time of publication (2011). The broader challenge of peptide-drug conjugate stability and pharmacokinetics is acknowledged but not fully resolved."},{"rthcId":"RPEP-01854","title":"gp100 peptide vaccine and interleukin-2 in patients with advanced melanoma.","authors":"Schwartzentruber, Douglas J; Lawson, David H; Richards, Jon M; Conry, Robert M; Miller, Donald M; Treisman, Jonathan; Gailani, Fawaz; Riley, Lee; Conlon, Kevin; Pockaj, Barbara; Kendra, Kari L; White, Richard L; Gonzalez, Rene; Kuzel, Timothy M; Curti, Brendan; Leming, Phillip D; Whitman, Eric D; Balkissoon, Jai; Reintgen, Douglas S; Kaufman, Howard; Marincola, Francesco M; Merino, Maria J; Rosenberg, Steven A; Choyke, Peter; Vena, Don; Hwu, Patrick","year":2011,"journal":"The New England journal of medicine, 364(22), 2119-27","doi":"10.1056/NEJMoa1012863","pmid":"21631324","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01855","title":"Orexin is required for brown adipose tissue development, differentiation, and function.","authors":"Sellayah, Dyan; Bharaj, Preeti; Sikder, Devanjan","year":2011,"journal":"Cell metabolism, 14(4), 478-90","doi":"10.1016/j.cmet.2011.08.010","pmid":"21982708","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01856","title":"A selective, non-peptide CRF receptor 1 antagonist prevents sodium lactate-induced acute panic-like responses.","authors":"Shekhar, Anantha; Johnson, Philip L; Fitz, Stephanie D; Nakazato, Atsuro; Chaki, Shigeyuki; Steckler, Thomas; Schmidt, Mark","year":2011,"journal":"The international journal of neuropsychopharmacology, 14(3), 355-65","doi":"10.1017/S1461145710001355","pmid":"21087553","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01857","title":"Matrix metalloproteinase-8 and substance P levels in gingival crevicular fluid during endodontic treatment of painful, nonvital teeth.","authors":"Shin, Su-Jung; Lee, Woocheol; Lee, Jae-Il; Baek, Seung-Ho; Kum, Kee-Yeon; Shon, Won-Jun; Bae, Kwang-Shik","year":2011,"journal":"Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics, 112(4), 548-54","doi":"10.1016/j.tripleo.2011.04.026","pmid":"21831678","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01858","title":"GHRH antagonist MZ-5-156 increases the expression of AMPK in A549 lung cancer cells.","authors":"Siejka, Agnieszka; Barabutis, Nektarios; Schally, Andrew V","year":2011,"journal":"Cell cycle (Georgetown, Tex.), 10(21), 3714-8","doi":"10.4161/cc.10.21.17904","pmid":"22041656","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01859","title":"Stable gastric pentadecapeptide BPC 157: novel therapy in gastrointestinal tract.","authors":"Sikiric, Predrag; Seiwerth, Sven; Rucman, Rudolf; Turkovic, Branko; Rokotov, Dinko Stancic; Brcic, Luka; Sever, Marko; Klicek, Robert; Radic, Bozo; Drmic, Domagoj; Ilic, Spomenko; Kolenc, Danijela; Vrcic, Hrvoje; Sebecic, Bozidar","year":2011,"journal":"Current pharmaceutical design, 17(16), 1612-32","doi":null,"pmid":"21548867","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01860","title":"Effect of inhibitor and activator of ghrelin receptor (GHS-R1a) on porcine ovarian granulosa cell functions.","authors":"Sirotkin, Alexander V; Meszarošová, Monika; Grossmann, Roland; Benčo, Andrej; Valenzuela, Francisco","year":2011,"journal":"General and comparative endocrinology, 173(1), 105-10","doi":"10.1016/j.ygcen.2011.05.001","pmid":"21600209","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01861","title":"Liraglutide: clinical pharmacology and considerations for therapy.","authors":"Sisson, Evan M","year":2011,"journal":"Pharmacotherapy, 31(9), 896-911","doi":"10.1592/phco.31.9.896","pmid":"21923591","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01862","title":"Anti-cyclic citrullinated peptide antibodies in adult patients with juvenile idiopathic arthritis.","authors":"Skare, Thelma S; Nisihara, Renato M; Silva, Rafael Mourato; Munhoz da Silva, Danilo J; Gameiro Silva, Marilia B; Utiyama, Shirley R R","year":2011,"journal":"Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases, 17(8), 421-3","doi":"10.1097/RHU.0b013e31823a4d0a","pmid":"22089992","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01863","title":"Cyclotides: a patent review.","authors":"Smith, Amanda B; Daly, Norelle L; Craik, David J","year":2011,"journal":"Expert opinion on therapeutic patents, 21(11), 1657-72","doi":"10.1517/13543776.2011.620606","pmid":"22017409","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01864","title":"Neural progenitor cells survival and neuronal differentiation in peptide-based hydrogels.","authors":"Song, Yulin; Li, Yixiu; Zheng, Qixin; Wu, Kai; Guo, Xiaodong; Wu, Yongchao; Yin, Ming; Wu, Qing; Fu, Xiaoling","year":2011,"journal":"Journal of biomaterials science. Polymer edition, 22(4-6), 475-87","doi":"10.1163/092050610X487756","pmid":"20566041","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01865","title":"Neuropeptides as pleiotropic modulators of the immune response.","authors":"Souza-Moreira, Luciana; Campos-Salinas, Jenny; Caro, Marta; Gonzalez-Rey, Elena","year":2011,"journal":"Neuroendocrinology, 94(2), 89-100","doi":"10.1159/000328636","pmid":"21734355","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01866","title":"Effects of a growth hormone-releasing hormone analog on endogenous GH pulsatility and insulin sensitivity in healthy men.","authors":"Stanley, Takara L; Chen, Cindy Y; Branch, Karen L; Makimura, Hideo; Grinspoon, Steven K","year":2011,"journal":"The Journal of clinical endocrinology and metabolism, 96(1), 150-8","doi":"10.1210/jc.2010-1587","pmid":"20943777","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tesamorelin 2 mg daily for 2 weeks significantly increased:\n- Mean overnight GH (+0.5 μg/liter, p = 0.004)\n- Average GH peak area (p = 0.001)\n- Basal GH secretion (+0.008 μg/liter·min, p = 0.008)\n- IGF-1 (+181 μg/liter, p < 0.0001)\n\nCritically, insulin-stimulated glucose uptake (measured by gold-standard euglycemic clamp) was not significantly affected (p = 0.61), and fasting glucose remained stable (p = 0.93). This demonstrates that GHRH-mediated GH augmentation preserves insulin sensitivity, unlike exogenous GH administration which can worsen insulin resistance.","whyItMatters":"People with excess belly fat have reduced growth hormone secretion, which may contribute to metabolic problems. Direct GH replacement can worsen insulin resistance, creating a therapeutic dilemma. Tesamorelin — by stimulating the body's own GH production through its natural pulsatile pattern — offers a potentially safer alternative. This study's demonstration of preserved insulin sensitivity is crucial for the drug's clinical application, particularly in metabolically vulnerable populations.","specificNumbers":"","methodology":"Open-label clinical study in 13 healthy males (mean age 45, mean BMI 27.3). Participants received tesamorelin 2 mg subcutaneously daily for 2 weeks, with assessments at baseline, end of treatment, and after 2 weeks of washout. GH pulsatility was measured via overnight frequent blood sampling. Insulin sensitivity was assessed using the gold-standard euglycemic hyperinsulinemic clamp technique.","limitations":"Very small sample size (n=13) of healthy men only, limiting generalizability. The 2-week treatment period is short and does not capture long-term effects. The study lacked a placebo control group. Only healthy men were studied; effects in populations with GH deficiency, obesity, or HIV lipodystrophy (the approved indication) may differ. Pulse frequency was not significantly affected, only pulse amplitude and basal secretion."},{"rthcId":"RPEP-01867","title":"Interaction between gastric and upper small intestinal hormones in the regulation of hunger and satiety: ghrelin and cholecystokinin take the central stage.","authors":"Stengel, Andreas; Taché, Yvette","year":2011,"journal":"Current protein & peptide science, 12(4), 293-304","doi":null,"pmid":"21428875","tags":["ghrelin","cholecystokinin","appetite-regulation","gut-peptides"],"studyType":"review","evidenceStrength":"review","keyFinding":"This review maps how gut peptides from the stomach and upper small intestine work together to control hunger and fullness. Ghrelin, produced in stomach X/A-like cells, is the only known peripheral hormone that stimulates appetite. Cholecystokinin (CCK) from the duodenum is its main counterpart, suppressing appetite. These two peptides interact directly, creating a regulatory network at the first point of nutrient contact.\n\nSeveral other peptides — including leptin, urocortin 2, amylin, and GLP-1 — amplify CCK's satiety signal through synergistic interactions. The review also highlights newer peptides discovered in the same stomach cells as ghrelin: obestatin (from the pro-ghrelin gene) and nesfatin-1 (from the nucleobindin2 gene), both under investigation for appetite regulation.","whyItMatters":"Understanding the peptide network that controls hunger and satiety is the scientific foundation behind modern weight loss drugs like GLP-1 agonists (semaglutide, tirzepatide). This review explains why appetite regulation isn't controlled by a single hormone but by a complex web of interacting gut peptides — and why drugs targeting multiple pathways simultaneously may be more effective than single-target approaches.","specificNumbers":"","methodology":"Narrative review of the scientific literature on gastric and upper small intestinal peptide hormones involved in appetite regulation, their central nervous system targets (brainstem, hypothalamus), and their interactions.","limitations":"Published in 2011, so it predates many recent developments in GLP-1 agonist therapeutics and newer discoveries in gut-brain peptide signaling. As a narrative review, it synthesizes existing evidence rather than generating new data."},{"rthcId":"RPEP-01868","title":"Effects of a single dose of exenatide on appetite, gut hormones, and glucose homeostasis in adults with Prader-Willi syndrome.","authors":"Sze, Lisa; Purtell, Louise; Jenkins, Arthur; Loughnan, Georgina; Smith, Ellie; Herzog, Herbert; Sainsbury, Amanda; Steinbeck, Katharine; Campbell, Lesley V; Viardot, Alexander","year":2011,"journal":"The Journal of clinical endocrinology and metabolism, 96(8), E1314-9","doi":"10.1210/jc.2011-0038","pmid":"21632815","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01869","title":"Mitochondria-targeted peptide accelerates ATP recovery and reduces ischemic kidney injury.","authors":"Szeto, Hazel H; Liu, Shaoyi; Soong, Yi; Wu, Dunli; Darrah, Shaun F; Cheng, Feng-Ying; Zhao, Zhihong; Ganger, Michael; Tow, Clara Y; Seshan, Surya V","year":2011,"journal":"Journal of the American Society of Nephrology : JASN, 22(6), 1041-52","doi":"10.1681/ASN.2010080808","pmid":"21546574","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01870","title":"Structural features governing the activity of lactoferricin-derived peptides that act in synergy with antibiotics against Pseudomonas aeruginosa in vitro and in vivo.","authors":"Sánchez-Gómez, Susana; Japelj, Bostjan; Jerala, Roman; Moriyón, Ignacio; Fernández Alonso, Mirian; Leiva, José; Blondelle, Sylvie E; Andrä, Jörg; Brandenburg, Klaus; Lohner, Karl; Martínez de Tejada, Guillermo","year":2011,"journal":"Antimicrobial agents and chemotherapy, 55(1), 218-28","doi":"10.1128/AAC.00904-10","pmid":"20956602","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01871","title":"Targeting VIP and PACAP receptor signalling: new therapeutic strategies in multiple sclerosis.","authors":"Tan, Yossan-Var; Waschek, James A","year":2011,"journal":"ASN neuro, 3(4)","doi":"10.1042/AN20110024","pmid":"21895607","tags":[],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"VIP (vasoactive intestinal peptide) and PACAP (pituitary adenylate cyclase-activating peptide) have dual properties that make them attractive therapeutic candidates for multiple sclerosis: they are both potent anti-inflammatory agents and neuroprotective molecules. Both peptides showed significant activity in the EAE (experimental autoimmune encephalomyelitis) animal model of MS.\n\nCurrent MS drugs primarily target the immune system and work well at early stages but do little to prevent the neurodegeneration that causes permanent disability. VIP and PACAP could potentially address both components — calming the autoimmune attack and directly protecting nerve cells from damage. The review extensively maps the structure-activity relationships of these peptides with their receptors, laying groundwork for designing improved analogs.","whyItMatters":"Multiple sclerosis affects approximately 2.5 million people worldwide, and current treatments largely fail to prevent the neurodegenerative component that causes permanent disability. VIP and PACAP represent a fundamentally different therapeutic approach because they simultaneously address inflammation and neurodegeneration — the two hallmarks of MS. Understanding how these peptides interact with their receptors at the molecular level is essential for developing stable, drug-like analogs that could reach clinical trials.","specificNumbers":"~2.5 million MS patients worldwide · EAE animal model data · VIP and PACAP both active · Dual anti-inflammatory + neuroprotective mechanisms","methodology":"This is a comprehensive narrative review covering the immunomodulatory and neuroprotective properties of VIP and PACAP, their receptor signaling pathways, and extensive structure-activity relationship data. It synthesizes evidence from animal models of MS (EAE), in vitro studies, and biophysical interaction studies of peptide-receptor binding.","limitations":"All MS-related efficacy data discussed comes from animal models (EAE), not human clinical trials. VIP and PACAP have short half-lives in the body, which is a major obstacle to therapeutic use. The review is from 2011, and the MS treatment landscape has changed significantly with newer disease-modifying therapies."},{"rthcId":"RPEP-01872","title":"Doping control analysis of selected peptide hormones using LC-MS(/MS).","authors":"Thevis, Mario; Thomas, Andreas; Schänzer, Wilhelm","year":2011,"journal":"Forensic science international, 213(1-3), 35-41","doi":"10.1016/j.forsciint.2011.06.015","pmid":"21752560","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01873","title":"Determination of growth hormone releasing peptides (GHRP) and their major metabolites in human urine for doping controls by means of liquid chromatography mass spectrometry.","authors":"Thomas, Andreas; Höppner, Sebastian; Geyer, Hans; Schänzer, Wilhelm; Petrou, Michael; Kwiatkowska, Dorota; Pokrywka, Andrzej; Thevis, Mario","year":2011,"journal":"Analytical and bioanalytical chemistry, 401(2), 507-16","doi":"10.1007/s00216-011-4702-3","pmid":"21298258","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01874","title":"B-type natriuretic peptide: diagnostic and therapeutic applications in infants and children.","authors":"Tobias, Joseph D","year":2011,"journal":"Journal of intensive care medicine, 26(3), 183-95","doi":"10.1177/0885066610387993","pmid":"21320863","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The natriuretic peptide system (including ANP and BNP) regulates fluid balance and blood vessel resistance. BNP assays serve diagnostic and prognostic purposes across various pediatric clinical scenarios including heart failure, congenital heart disease, and post-surgical management. Recombinant BNP (nesiritide) produced through DNA technology is available for therapeutic use. The review covers BNP physiology, diagnostic applications in pediatrics, and emerging reports of recombinant BNP treatment in the pediatric population.","whyItMatters":"Diagnosing and managing heart disease in infants and children is particularly challenging because symptoms often overlap with other conditions. BNP levels provide an objective, measurable indicator of cardiac stress that can guide decisions in pediatric intensive care. The availability of recombinant BNP as a therapeutic peptide adds a treatment option for pediatric heart failure that directly replaces what the body should be producing — a physiological approach to therapy.","specificNumbers":"","methodology":"Narrative review of published literature covering the physiology of the natriuretic peptide system, clinical applications of BNP monitoring as a diagnostic biomarker in pediatric patients, and reports of recombinant BNP (nesiritide) therapeutic use in infants and children.","limitations":"Published in 2011, the review predates significant advances in both BNP diagnostic thresholds and nesiritide clinical evidence. The pediatric evidence base for recombinant BNP therapy was limited to case reports and small series at the time. Nesiritide's adult clinical profile has been debated (the ASCEND-HF trial showed modest benefits), which may affect enthusiasm for pediatric use. Age-specific BNP reference ranges were still being established. The review is a single-author narrative without systematic methodology."},{"rthcId":"RPEP-01875","title":"Infusions of neuropeptide Y into the lateral septum reduce anxiety-related behaviors in the rat.","authors":"Trent, Natalie L; Menard, Janet L","year":2011,"journal":"Pharmacology, biochemistry, and behavior, 99(4), 580-90","doi":"10.1016/j.pbb.2011.06.009","pmid":"21693128","tags":["neuropeptide-y","anxiety"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Infusing neuropeptide Y (NPY) directly into the lateral septum — a brain region rich in NPY and involved in anxiety regulation — reduced anxiety-related behavior in rats across two of three behavioral tests.\n\nIn the novelty-induced suppression of feeding test, NPY-treated rats ate sooner in an unfamiliar environment (an anxiety measure independent of appetite changes). In the shock-probe burying test, NPY reduced defensive burying behavior. However, NPY had no effect on the elevated plus-maze.\n\nCritically, blocking the Y1 receptor with the antagonist BIBO 3304 reversed NPY's anti-anxiety effect in the feeding test but not in the shock-probe test. This suggests NPY reduces different types of anxiety through different receptor mechanisms in the lateral septum — Y1-dependent for some anxiety behaviors and Y1-independent for others.","whyItMatters":"NPY is known to reduce anxiety when broadly administered to the brain, but this study pinpoints the lateral septum as a specific site of action and shows the mechanism is more complex than previously thought. Different types of anxiety appear to be regulated by different NPY receptors in the same brain region. This has implications for developing targeted anti-anxiety treatments based on neuropeptide Y pathways.","specificNumbers":"1.5 μg NPY dose · BIBO 3304 at 0.15 and 0.30 μg · 3 anxiety tests · 2 of 3 tests showed anxiolysis · Y1 blockade reversed 1 of 2 effects","methodology":"Two experiments in male Long-Evans rats. Experiment 1: NPY (1.5 μg) was infused into the lateral septum, and rats were tested on three anxiety paradigms (elevated plus-maze, novelty-induced suppression of feeding, shock-probe burying). Experiment 2: the Y1 receptor antagonist BIBO 3304 was co-infused with NPY to determine Y1 receptor involvement.","limitations":"Rat study using direct brain injection, which is not clinically practical. NPY was tested at only one dose. The elevated plus-maze showed no effect, suggesting the lateral septum's role in anxiety may be test-specific. Results may not translate directly to human anxiety disorders."},{"rthcId":"RPEP-01876","title":"Functional links between Aβ toxicity, endocytic trafficking, and Alzheimer's disease risk factors in yeast.","authors":"Treusch, Sebastian; Hamamichi, Shusei; Goodman, Jessica L; Matlack, Kent E S; Chung, Chee Yeun; Baru, Valeriya; Shulman, Joshua M; Parrado, Antonio; Bevis, Brooke J; Valastyan, Julie S; Han, Haesun; Lindhagen-Persson, Malin; Reiman, Eric M; Evans, Denis A; Bennett, David A; Olofsson, Anders; DeJager, Philip L; Tanzi, Rudolph E; Caldwell, Kim A; Caldwell, Guy A; Lindquist, Susan","year":2011,"journal":"Science (New York, N.Y.), 334(6060), 1241-5","doi":"10.1126/science.1213210","pmid":"22033521","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01877","title":"Identification of lactoferricin B intracellular targets using an Escherichia coli proteome chip.","authors":"Tu, Yu-Hsuan; Ho, Yu-Hsuan; Chuang, Ying-Chih; Chen, Po-Chung; Chen, Chien-Sheng","year":2011,"journal":"PloS one, 6(12), e28197","doi":"10.1371/journal.pone.0028197","pmid":"22164243","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01878","title":"An orexinergic projection from perifornical hypothalamus to raphe pallidus increases rat brown adipose tissue thermogenesis.","authors":"Tupone, Domenico; Madden, Christopher J; Cano, Georgina; Morrison, Shaun F","year":2011,"journal":"The Journal of neuroscience : the official journal of the Society for Neuroscience, 31(44), 15944-55","doi":"10.1523/JNEUROSCI.3909-11.2011","pmid":"22049437","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01879","title":"Mutational analysis of predicted extracellular domains of human growth hormone secretagogue receptor 1a.","authors":"Ueda, Teruhisa; Matsuura, Bunzo; Miyake, Teruki; Furukawa, Shinya; Abe, Masanori; Hiasa, Yoichi; Onji, Morikazu","year":2011,"journal":"Regulatory peptides, 166(1-3), 28-35","doi":"10.1016/j.regpep.2010.08.002","pmid":"20727371","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01880","title":"Complex regulation of GH autofeedback under dual-peptide drive: studies under a pharmacological GH and sex steroid clamp.","authors":"Veldhuis, Johannes D; Erickson, Dana; Miles, John M; Bowers, Cyril Y","year":2011,"journal":"American journal of physiology. Endocrinology and metabolism, 300(6), E1158-65","doi":"10.1152/ajpendo.00054.2011","pmid":"21467302","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In a randomized crossover study of 25 healthy older adults, sex differences, sex steroid supplementation (estradiol in women, testosterone in men), and combined GHRH/GHRP-2 peptide infusion each independently and significantly controlled GH autofeedback dynamics. Dual-peptide stimulation elevated nadir GH concentrations independently of sex steroids and sex (P=0.001). Women showed greater peak GH responses to the dual-peptide agonists than men (P=0.016). Sex steroid treatment augmented peak GH recovery during saline infusion (P<0.001). All three factors — sex, sex steroids, and peptide drive — independently augmented peak GH recovery (each P≤0.005).","whyItMatters":"Growth hormone regulation becomes dysregulated with aging, contributing to changes in body composition, bone density, and metabolism. Understanding how peptide secretagogues (GHRH and GHRP-2) interact with sex steroids and sex differences to control GH pulsatility could inform more effective, personalized GH-axis therapies for age-related hormonal decline.","specificNumbers":"n=25 (11 women, 14 men) · dual-peptide nadir GH effect P=0.001 · sex steroid nadir effect P=0.003 · peak GH sex difference P=0.016 · sex steroid peak effect P<0.001 · sex steroid regularity effect P=0.012 · peptide regularity effect P<0.001","methodology":"Prospective, double-blind, randomized crossover study in 11 postmenopausal women and 14 older men. Each participant received a single IV GH pulse to enforce negative feedback, followed by continuous IV infusion of either saline or combined GHRH/GHRP-2 during pharmacological estradiol (women) or testosterone (men) supplementation versus placebo. Three-way ANCOVA analyzed sex, sex steroid, and peptide effects. Approximate entropy analysis assessed GH regularity.","limitations":"Small sample (25 participants). The pharmacological clamp approach uses supraphysiological conditions that may not reflect normal physiology. Only postmenopausal women and older men were studied, limiting generalizability to younger populations. Short-term study — long-term effects of dual-peptide stimulation were not assessed."},{"rthcId":"RPEP-01881","title":"Gender, sex-steroid, and secretagogue-selective recovery from growth hormone-induced feedback in older women and men.","authors":"Veldhuis, Johannes D; Erickson, Dana; Wigham, Jean; Weist, Sue; Miles, John M; Bowers, Cyril Y","year":2011,"journal":"The Journal of clinical endocrinology and metabolism, 96(8), 2540-7","doi":"10.1210/jc.2011-0298","pmid":"21613353","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01882","title":"Thymosin-alpha1 promotes the apoptosis of regulatory T cells and survival rate in septic mice.","authors":"Wan, Jian; Shan, Yi; Shan, Hongwei; Li, Guomin; Wang, Tao; Guan, Jun; Liu, Xuefeng; Chen, Dechang; Li, Wenfang; Lin, Zhaofen","year":2011,"journal":"Frontiers in bioscience (Landmark edition), 16(8), 3004-13","doi":null,"pmid":"21622217","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01883","title":"Thymosin alpha 1 is associated with improved cellular immunity and reduced infection rate in severe acute pancreatitis patients in a double-blind randomized control study.","authors":"Wang, Xinying; Li, Weiqin; Niu, Chenglin; Pan, Liya; Li, Ning; Li, Jieshou","year":2011,"journal":"Inflammation, 34(3), 198-202","doi":"10.1007/s10753-010-9224-1","pmid":"20549321","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01884","title":"Cloning, expression and patient IgE reactivity of recombinant Pru du 6, an 11S globulin from almond.","authors":"Willison, LeAnna N; Tripathi, Pallavi; Sharma, Girdhari; Teuber, Suzanne S; Sathe, Shridhar K; Roux, Kenneth H","year":2011,"journal":"International archives of allergy and immunology, 156(3), 267-81","doi":"10.1159/000323887","pmid":"21720172","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01885","title":"Thymic peptides for treatment of cancer patients.","authors":"Wolf, Elke; Milazzo, Stefania; Boehm, Katja; Zwahlen, Marcel; Horneber, Markus","year":2011,"journal":"The Cochrane database of systematic reviews, 2011(2), CD003993","doi":"10.1002/14651858.CD003993.pub3","pmid":"21328265","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01886","title":"Development and preliminary clinical evaluation of a peptide immunotherapy vaccine for cat allergy.","authors":"Worm, Margitta; Lee, Hae-Hyuk; Kleine-Tebbe, Jörg; Hafner, Roderick P; Laidler, Paul; Healey, David; Buhot, Cecile; Verhoef, Adrienne; Maillère, Bernard; Kay, A Barry; Larché, Mark","year":2011,"journal":"The Journal of allergy and clinical immunology, 127(1), 89-97, 97.e1-14","doi":"10.1016/j.jaci.2010.11.029","pmid":"21211644","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01887","title":"Ghrelin inhibits AGEs-induced apoptosis in human endothelial cells involving ERK1/2 and PI3K/Akt pathways.","authors":"Xiang, Ying; Li, Qiang; Li, Menglan; Wang, Wei; Cui, Can; Zhang, Jinchao","year":2011,"journal":"Cell biochemistry and function, 29(2), 149-55","doi":"10.1002/cbf.1736","pmid":"21370247","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01888","title":"VPAC1 (vasoactive intestinal peptide (VIP) receptor type 1) G protein-coupled receptor mediation of VIP enhancement of murine experimental colitis.","authors":"Yadav, Mahesh; Huang, Mei-Chuan; Goetzl, Edward J","year":2011,"journal":"Cellular immunology, 267(2), 124-32","doi":"10.1016/j.cellimm.2011.01.001","pmid":"21295288","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01889","title":"Oxytocin in the periaqueductal gray participates in pain modulation in the rat by influencing endogenous opiate peptides.","authors":"Yang, Jun; Liang, Jin-Ying; Li, Peng; Pan, Yan-Juan; Qiu, Pei-Yong; Zhang, Jing; Hao, Fang; Wang, Da-Xin","year":2011,"journal":"Peptides, 32(6), 1255-61","doi":"10.1016/j.peptides.2011.03.007","pmid":"21439337","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Four key findings emerged: (1) Pain stimulation increased PAG concentrations of oxytocin, leucine-enkephalin, methionine-enkephalin, and β-endorphin, but not dynorphin A(1-13). (2) Blocking oxytocin receptors in the PAG decreased levels of the three enkephalins/endorphin but not dynorphin. (3) The pain-relieving effect of oxytocin in the PAG was reversed by naloxone, an opioid receptor antagonist. (4) Exogenous oxytocin administration increased PAG levels of leucine-enkephalin, methionine-enkephalin, and β-endorphin, but not dynorphin.\n\nTogether, this demonstrates that oxytocin's pain-modulating role in the PAG is mediated through enkephalin and endorphin peptides, but not dynorphin.","whyItMatters":"Understanding how oxytocin reduces pain through the endogenous opioid system opens potential therapeutic avenues. If oxytocin can stimulate the brain's natural painkillers, it might provide pain relief without the addiction risk of synthetic opioids. The specific identification of which opioid peptides respond to oxytocin (enkephalins and β-endorphin, not dynorphin) provides molecular targets for future research.","specificNumbers":"","methodology":"Rats received PAG microdialysis catheterization to measure local peptide concentrations. Pain stimulation was applied while collecting perfusion fluid samples. Experiments tested the effects of intra-PAG oxytocin injection, oxytocin receptor antagonist, and the opioid antagonist naloxone on endogenous opioid peptide levels and pain thresholds. Peptide concentrations were measured by radioimmunoassay.","limitations":"The study was conducted in rats using direct brain injections, which is not a clinically feasible delivery method. The PAG microdialysis technique measures local peptide concentrations but may not reflect broader brain-wide changes. The findings may not directly translate to human pain processing. Specific quantitative changes in peptide levels are not reported in the abstract."},{"rthcId":"RPEP-01890","title":"Lactoferrin: an iron-binding antimicrobial protein against Escherichia coli infection.","authors":"Yen, Chih-Ching; Shen, Chih-Jie; Hsu, Wu-Huei; Chang, Yi-Hsin; Lin, Hsin-Tang; Chen, Hsiao-Ling; Chen, Chuan-Mu","year":2011,"journal":"Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine, 24(4), 585-94","doi":"10.1007/s10534-011-9423-8","pmid":"21327478","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01891","title":"Early and late effects of the DPP-4 inhibitor vildagliptin in a rat model of post-myocardial infarction heart failure.","authors":"Yin, Meimei; Silljé, Herman H W; Meissner, Maxi; van Gilst, Wiek H; de Boer, Rudolf A","year":2011,"journal":"Cardiovascular diabetology, 10, 85","doi":"10.1186/1475-2840-10-85","pmid":"21955567","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Vildagliptin inhibited DPP-4 enzymatic activity by approximately 70% and increased active GLP-1 levels roughly 3-fold in plasma (p < 0.05 vs. untreated groups). However, ejection fraction remained equally depressed in all three MI groups compared to sham controls, regardless of whether vildagliptin was started immediately or three weeks after the heart attack.\n\nStress biomarkers ANP and BNP mRNA were elevated in all MI groups with no significant reduction from vildagliptin treatment. The drug also had no effect on cardiomyocyte size, capillary density, glucose levels, or body weight.","whyItMatters":"GLP-1 peptides have shown promise as cardioprotective agents, sparking interest in whether DPP-4 inhibitors — which raise GLP-1 by preventing its breakdown — could protect the heart after a heart attack. This study provides important negative evidence, suggesting that the modest GLP-1 increases achieved through DPP-4 inhibition may not reach the therapeutic threshold needed for cardiac protection, pointing researchers toward direct GLP-1 analogs or higher-potency approaches instead.","specificNumbers":"","methodology":"Sprague-Dawley rats underwent coronary artery ligation to induce a heart attack or sham surgery. Some MI rats received vildagliptin (15 mg/kg/day) starting 2 days before surgery (early treatment), while others started treatment 3 weeks after surgery (late treatment). Controls received no drug. At 12 weeks, researchers assessed heart function using echocardiography and invasive hemodynamic measurements, and performed molecular and tissue analysis.","limitations":"This was an animal study in rats, so results may not directly translate to humans. The study used a single dose of vildagliptin and did not test higher doses that might produce stronger effects. The sample size was not reported in the abstract. Additionally, rats were not diabetic, so the drug's cardiac effects in the context of diabetes remain untested here."},{"rthcId":"RPEP-01892","title":"Translational studies on PYY as a novel target in obesity.","authors":"Zac-Varghese, Sagen; De Silva, Akila; Bloom, Stephen R","year":2011,"journal":"Current opinion in pharmacology, 11(6), 582-5","doi":"10.1016/j.coph.2011.10.001","pmid":"22019565","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01893","title":"Studies on lactoferricin-derived Escherichia coli membrane-active peptides reveal differences in the mechanism of N-acylated versus nonacylated peptides.","authors":"Zweytick, Dagmar; Deutsch, Günter; Andrä, Jörg; Blondelle, Sylvie E; Vollmer, Ekkehard; Jerala, Roman; Lohner, Karl","year":2011,"journal":"The Journal of biological chemistry, 286(24), 21266-76","doi":"10.1074/jbc.M110.195412","pmid":"21515687","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Engineered LF11 variants with enhanced hydrophobicity (via bulky amino acid addition or N-acylation) showed improved antimicrobial activity against E. coli that correlated with their ability to perturb bacterial membrane mimics.\n\nNon-acylated and N-acylated peptides worked through distinct mechanisms: non-acylated peptides induced segregation of peptide-rich and peptide-poor lipid domains, while N-acylated peptides formed small heterogeneous domains with greater packing defects. N-acylated peptides also perturbed neutral lipid packing and increased membrane permeability, but their elevated binding to lipopolysaccharides partially counteracted this advantage. Both types increased membrane curvature stress. Transmission electron microscopy showed N-acylated peptides induced tubular outer membrane protrusions, and viability tests confirmed bacteria died before visible cell lysis.","whyItMatters":"With antibiotic resistance rising, antimicrobial peptides derived from human immune proteins like lactoferricin represent a promising alternative. Understanding exactly how different modifications change the killing mechanism is essential for rational design of next-generation peptide antibiotics. The finding that bacteria die before lysis suggests these peptides could minimize endotoxin release during treatment.","specificNumbers":"","methodology":"The researchers designed LF11 mutant peptides based on its known lipid-environment structure. They tested antimicrobial activity against E. coli, studied membrane interactions using bacterial membrane mimics with differential scanning calorimetry and lipid domain analysis, measured E. coli lipid vesicle permeability, and visualized bacterial membrane changes with transmission electron microscopy. Viability assays determined the timing of cell death relative to lysis.","limitations":"All experiments were conducted in vitro using E. coli and membrane models. The peptides' efficacy, stability, and toxicity in animal models or human infections were not tested. The interaction with lipopolysaccharides that partially counteracted N-acylated peptide activity could be a significant limitation in clinical applications. Hemolysis and toxicity to human cells were noted in mesh terms but not discussed in the abstract."},{"rthcId":"RPEP-01894","title":"Willbold 2012 D3 Peptide Amyloid Oral","authors":"","year":2012,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01895","title":"Bovine lactoferrin-derived peptides as novel broad-spectrum inhibitors of influenza virus.","authors":"Ammendolia, Maria Grazia; Agamennone, Mariangela; Pietrantoni, Agostina; Lannutti, Fabio; Siciliano, Rosa Anna; De Giulio, Beatrice; Amici, Carla; Superti, Fabiana","year":2012,"journal":"Pathogens and global health, 106(1), 12-9","doi":"10.1179/2047773212Y.0000000004","pmid":"22595270","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The antiviral activity of bovine lactoferrin against influenza is entirely attributable to its C-lobe, which binds specifically to the HA2 region of viral hemagglutinin — the highly conserved domain containing the fusion peptide. All major virus subtypes tested (including H1N1 and H3N2) were inhibited.\n\nThrough molecular docking studies, three C-lobe peptide fragments were identified that inhibited both virus hemagglutination and cell infection at femtomolar concentrations — an extremely potent level of activity. The target (the fusion peptide region) is conserved across influenza subtypes, explaining the broad-spectrum activity.","whyItMatters":"Influenza viruses mutate rapidly, making vaccines a yearly gamble and creating demand for broad-spectrum antivirals. These lactoferrin fragments target the fusion peptide — one of the most conserved parts of the virus that cannot easily mutate without losing function. Finding antiviral peptides that work at femtomolar concentrations against multiple flu subtypes is remarkable and could lead to new therapeutic approaches, especially during pandemic influenza strains.","specificNumbers":"","methodology":"Researchers split bovine lactoferrin into its N-lobe and C-lobe and tested each against multiple influenza subtypes. Far-western blotting and sequencing identified the viral binding site. Molecular docking studies were used to identify the most active peptide fragments from the C-lobe. Antiviral activity was measured by hemagglutination inhibition and cell infection assays using cultured cells.","limitations":"All experiments were conducted in vitro (cell culture and molecular modeling), not in animals or humans. Femtomolar potency in a test tube may not translate to in vivo efficacy due to peptide degradation, bioavailability challenges, and the complexity of actual infection. The study does not address toxicity, pharmacokinetics, or route of administration. Independent replication of the femtomolar potency claim would strengthen confidence in these findings."},{"rthcId":"RPEP-01896","title":"Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders: a randomized controlled trial.","authors":"Anagnostou, Evdokia; Soorya, Latha; Chaplin, William; Bartz, Jennifer; Halpern, Danielle; Wasserman, Stacey; Wang, A Ting; Pepa, Lauren; Tanel, Nadia; Kushki, Azadeh; Hollander, Eric","year":2012,"journal":"Molecular autism, 3(1), 16","doi":"10.1186/2040-2392-3-16","pmid":"23216716","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01897","title":"Chromogranin-A: a multifaceted cardiovascular role in health and disease.","authors":"Angelone, T; Mazza, R; Cerra, M C","year":2012,"journal":"Current medicinal chemistry, 19(24), 4042-50","doi":null,"pmid":"22834795","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01898","title":"Design of a novel antimicrobial peptide activated by virulent proteases.","authors":"Aoki, Wataru; Kitahara, Nao; Miura, Natsuko; Morisaka, Hironobu; Kuroda, Kouichi; Ueda, Mitsuyoshi","year":2012,"journal":"Chemical biology & drug design, 80(5), 725-33","doi":"10.1111/cbdd.12012","pmid":"22863111","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01899","title":"Endogenous opioids in wound-site neutrophils of sternotomy patients.","authors":"Awad, Hamdy; Abas, Motaz; Elgharably, Haytham; Tripathi, Ravi; Theofilos, Tykie; Bhandary, Sujatha; Sai-Sudhakar, Chittoor; Sen, Chandan K; Roy, Sashwati","year":2012,"journal":"PloS one, 7(10), e47569","doi":"10.1371/journal.pone.0047569","pmid":"23118879","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01900","title":"Effects of growth hormone–releasing hormone on cognitive function in adults with mild cognitive impairment and healthy older adults: results of a controlled trial.","authors":"Baker, Laura D; Barsness, Suzanne M; Borson, Soo; Merriam, George R; Friedman, Seth D; Craft, Suzanne; Vitiello, Michael V","year":2012,"journal":"Archives of neurology, 69(11), 1420-9","doi":null,"pmid":"22869065","tags":["ghrh","cognitive-function","aging"],"studyType":"Randomized Controlled Trial","evidenceStrength":"Strong","keyFinding":"Twenty weeks of daily GHRH (tesamorelin) injections improved cognitive function in both healthy older adults and those with mild cognitive impairment. The effect was statistically significant in the intent-to-treat analysis (P=.03) and even stronger among those who completed the full protocol (P=.002).\n\nThe cognitive benefit was most pronounced for executive function (P=.005), which includes skills like planning, mental flexibility, and multitasking. There was also a trend toward improvement in verbal memory (P=.08). The treatment boosted IGF-1 levels by 117% while keeping them within the normal physiological range, and reduced body fat by 7.4%. In adults with MCI, fasting insulin rose by 35% but remained within normal limits. Adverse events were mild, reported by 68% of those on GHRH versus 36% on placebo.","whyItMatters":"As people age, levels of GHRH, growth hormone, and IGF-1 naturally decline — and this decline is thought to contribute to cognitive deterioration and possibly Alzheimer's disease. This trial suggests that restoring GHRH signaling with a stabilized analog can meaningfully improve thinking skills in older adults, including those already showing early signs of cognitive decline. If confirmed in longer trials, this peptide-based approach could represent a new strategy for protecting brain health during aging.","specificNumbers":"n=152 · 20-week treatment · cognition improved P=.03 (ITT), P=.002 (completers) · executive function P=.005 · IGF-1 increased 117% · body fat reduced 7.4% · fasting insulin up 35% in MCI group","methodology":"This was a randomized, double-blind, placebo-controlled trial conducted at the University of Washington. A total of 152 adults aged 55–87 (66 with MCI, 86 healthy) self-administered daily subcutaneous injections of tesamorelin (1 mg/day) or placebo at bedtime for 20 weeks. Cognitive testing was done at baseline, weeks 10 and 20, and after a 10-week washout period. The battery included tests for executive function, verbal memory, and visual memory. Blood work and body composition scans were also performed.","limitations":"The 20-week treatment period was relatively short for evaluating long-term brain health effects. The study did not assess whether cognitive benefits persisted after the 10-week washout. Sample size, while reasonable for a controlled trial, was modest, especially when split between MCI and healthy subgroups. The study used tesamorelin, a stabilized GHRH analog, so results may not generalize to other GHRH-related peptides. Adverse events were mild but more common in the treatment group."},{"rthcId":"RPEP-01901","title":"Developmental experiences and the oxytocin receptor system.","authors":"Bales, Karen L; Perkeybile, Allison M","year":2012,"journal":"Hormones and behavior, 61(3), 313-9","doi":"10.1016/j.yhbeh.2011.12.013","pmid":"22245313","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01902","title":"Analytical challenges in the detection of peptide hormones for anti-doping purposes.","authors":"Barroso, Osquel; Handelsman, David J; Strasburger, Christian; Thevis, Mario","year":2012,"journal":"Bioanalysis, 4(13), 1577-90","doi":"10.4155/bio.12.128","pmid":"22831474","tags":[],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Detecting peptide hormone doping in athletes remains one of the hardest challenges in anti-doping science. Unlike small-molecule drugs that leave clear metabolic traces, peptide hormones like growth hormone, EPO, and insulin-like growth factor are nearly identical to substances the body produces naturally. The review describes advances in mass spectrometry-based detection methods and immunological assays for WADA-prohibited peptides, while noting that many peptide hormones still can't be reliably detected.\n\nThe most promising future direction is the development of 'biomarker' approaches — instead of trying to detect the peptide itself, scientists look for downstream biological changes that betray its use. This indirect detection strategy may be the key to catching peptide doping.","whyItMatters":"Peptide hormones are among the most commonly abused substances in elite sport, but they're also among the hardest to detect. As new synthetic peptides (like growth hormone secretagogues and GLP-1 agonists) become widely available, anti-doping labs face an ever-expanding list of targets. This review maps the state of detection technology and identifies critical gaps that athletes could exploit.","specificNumbers":"WADA Section S2 prohibited substances covered · MS-based and immunological assay methods reviewed · Biomarker-based detection approaches in development","methodology":"This is an expert review authored by researchers affiliated with WADA-accredited anti-doping laboratories. It surveys published analytical methods for detecting prohibited peptide hormones, evaluates the performance of mass spectrometry and immunoassay approaches, and discusses emerging biomarker-based detection strategies under development.","limitations":"As a 2012 review, the specific analytical methods described have evolved, though the fundamental challenges of peptide hormone detection remain relevant. The review focuses on detection capability rather than real-world prevalence of peptide doping, so the actual scale of the problem isn't quantified. Some newer peptides now used in sports weren't covered."},{"rthcId":"RPEP-01903","title":"Combined effects of aerobic exercise and high-carbohydrate meal on plasma acylated ghrelin and levels of hunger.","authors":"Becker, Geórgia Franco; Macedo, Rodrigo Cauduro Oliveira; Cunha, Giovani Dos Santos; Martins, Jocelito Bijoldo; Laitano, Orlando; Reischak-Oliveira, Alvaro","year":2012,"journal":"Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme, 37(1), 184-92","doi":"10.1139/h11-149","pmid":"22300359","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01904","title":"Changes in pain and insulin-like growth factor 1 in fibromyalgia during exercise: the involvement of cerebrospinal inflammatory factors and neuropeptides.","authors":"Bjersing, Jan L; Dehlin, Mats; Erlandsson, Malin; Bokarewa, Maria I; Mannerkorpi, Kaisa","year":2012,"journal":"Arthritis research & therapy, 14(4), R162","doi":"10.1186/ar3902","pmid":"22776095","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01905","title":"Chimerization of lactoferricin and lactoferrampin peptides strongly potentiates the killing activity against Candida albicans.","authors":"Bolscher, Jan; Nazmi, Kamran; van Marle, Jan; van 't Hof, Wim; Veerman, Enno","year":2012,"journal":"Biochemistry and cell biology = Biochimie et biologie cellulaire, 90(3), 378-88","doi":"10.1139/o11-085","pmid":"22364313","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01906","title":"Acromegaly induced by ectopic secretion of GHRH: a review 30 years after GHRH discovery.","authors":"Borson-Chazot, Françoise; Garby, Laetitia; Raverot, Gerald; Claustrat, Francine; Raverot, Véronique; Sassolas, Geneviève","year":2012,"journal":"Annales d'endocrinologie, 73(6), 497-502","doi":"10.1016/j.ando.2012.09.004","pmid":"23122576","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01907","title":"History to the discovery of ghrelin.","authors":"Bowers, Cyril Y","year":2012,"journal":"Methods in enzymology, 514, 3-32","doi":"10.1016/B978-0-12-381272-8.00001-5","pmid":"22975043","tags":["ghrelin","growth-hormone","peptide-history"],"studyType":"historical-review","evidenceStrength":"review-narrative","keyFinding":"This historical review traces the 26-year journey from the first synthetic growth hormone-releasing peptides (GHRPs) in 1976 to the isolation of ghrelin from the stomach in 1999. Key milestones: somatostatin isolation (1973), discovery of unnatural GHRPs (1976), GHRH isolation (1982), the hypothesis that GHRPs reflect a new, undiscovered hormone (1984), demonstration of GHRP+GHRH synergy in humans (1990), discovery and cloning of the GHS/GHRP receptor (1996–1998), and finally ghrelin's isolation and identification by Kojima and Kangawa (1999).\n\nA critical insight was that GHRPs release more growth hormone than GHRH when given intravenously in humans, but the reverse is true in laboratory cell cultures — suggesting GHRPs act on both the hypothalamus and pituitary, not just the pituitary. GHRPs are active by multiple routes (IV, subcutaneous, oral, intranasal), and ghrelin turned out to be pleiotropic, affecting not just growth hormone but also appetite, metabolism, cardiovascular function, immunity, and inflammation.","whyItMatters":"Ghrelin's discovery fundamentally changed our understanding of growth hormone regulation and appetite control. Written by Cyril Bowers — the researcher who discovered GHRPs and drove much of this field for decades — this review provides a first-person account of how synthetic peptides led to the discovery of one of the body's most important hormones. The ghrelin system is now central to research on obesity, cachexia, growth disorders, and metabolic disease.","specificNumbers":"1976: first GHRPs discovered · 1999: ghrelin isolated from stomach · GHRP+GHRH synergy demonstrated in humans · GHRPs active via IV, SC, oral, intranasal routes · Ghrelin system conserved since zebrafish evolution","methodology":"Historical narrative review written by one of the field's pioneers, chronicling key experiments, discoveries, and conceptual developments from 1973 to the present across basic science, animal studies, and clinical research.","limitations":"This is a historical narrative from the perspective of one of the field's principal investigators. While comprehensive, it naturally emphasizes the author's contributions and perspective. It is not a systematic review and does not critically appraise the quality of individual studies."},{"rthcId":"RPEP-01908","title":"Does cholesterol play a role in the bacterial selectivity of antimicrobial peptides?","authors":"Brender, Jeffrey R; McHenry, Austin J; Ramamoorthy, Ayyalusamy","year":2012,"journal":"Frontiers in immunology, 3, 195","doi":"10.3389/fimmu.2012.00195","pmid":"22822405","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01909","title":"Effects of fat, protein, and carbohydrate and protein load on appetite, plasma cholecystokinin, peptide YY, and ghrelin, and energy intake in lean and obese men.","authors":"Brennan, Ixchel M; Luscombe-Marsh, Natalie D; Seimon, Radhika V; Otto, Bärbel; Horowitz, Michael; Wishart, Judith M; Feinle-Bisset, Christine","year":2012,"journal":"American journal of physiology. Gastrointestinal and liver physiology, 303(1), G129-40","doi":"10.1152/ajpgi.00478.2011","pmid":"22556143","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01910","title":"Search for novel therapies for triple negative breast cancers (TNBC): analogs of luteinizing hormone-releasing hormone (LHRH) and growth hormone-releasing hormone (GHRH).","authors":"Buchholz, Stefan; Seitz, Stephan; Engel, Jörg B; Montero, Alberto; Ortmann, Olaf; Perez, Roberto; Block, Norman L; Schally, Andrew V","year":2012,"journal":"Hormone molecular biology and clinical investigation, 9(1), 87-94","doi":"10.1515/hmbci-2011-0002","pmid":"25961354","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A substantial proportion of triple-negative breast cancers express receptors for both LHRH and GHRH, providing potential therapeutic targets. Potent antagonists of both GHRH and LHRH receptors have been developed and shown to inhibit tumor growth, tumorigenicity, and metastatic potential in experimental cancer models.\n\nThe targeted cytotoxic LHRH analog AN-152 (AEZS-108), which conjugates the chemotherapy drug doxorubicin to an LHRH peptide, delivers chemotherapy directly to LHRH receptor-expressing cancer cells. This approach could provide targeted treatment for TNBC while reducing systemic toxicity. The authors conclude that experimental evidence supports clinical trials with LHRH antagonists and AN-152 in TNBC patients.","whyItMatters":"TNBC accounts for about 15-20% of breast cancers and has the worst prognosis because it lacks the molecular targets (ER, PR, HER2) used by most breast cancer drugs. Chemotherapy is the only systemic option but responses are disappointing. Peptide hormone receptor-based therapies could provide the first targeted treatments for this aggressive cancer, potentially improving outcomes while reducing the side effects of untargeted chemotherapy.","specificNumbers":"","methodology":"Review of experimental and preclinical studies examining the expression of LHRH and GHRH receptors in TNBC, and the antitumor effects of LHRH antagonists, GHRH antagonists, and the targeted cytotoxic LHRH analog AN-152 (AEZS-108) in cancer models.","limitations":"This is a review of preclinical and experimental data — no clinical trial results are presented. The proportion of TNBC tumors that express sufficient LHRH/GHRH receptors for therapy is not precisely quantified. Clinical translation of peptide-based cancer therapies faces challenges including receptor heterogeneity, peptide stability, and achieving adequate tumor penetration. The publication is from 2012, and subsequent clinical trials may have provided additional data."},{"rthcId":"RPEP-01911","title":"Roux-en-Y gastric bypass operation in rats.","authors":"Bueter, Marco; Abegg, Kathrin; Seyfried, Florian; Lutz, Thomas A; le Roux, Carel W","year":2012,"journal":"Journal of visualized experiments : JoVE, e3940","doi":"10.3791/3940","pmid":"22710348","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01912","title":"Obesity in patients with Bardet-Biedl syndrome: influence of appetite-regulating hormones.","authors":"Büscher, Anja K; Cetiner, Metin; Büscher, Rainer; Wingen, Anne-Margret; Hauffa, Berthold P; Hoyer, Peter F","year":2012,"journal":"Pediatric nephrology (Berlin, Germany), 27(11), 2065-2071","doi":"10.1007/s00467-012-2220-y","pmid":"22669322","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BBS patients had significantly higher BMI than controls. Plasma levels of acylated ghrelin, total ghrelin, and obestatin were slightly elevated compared to controls, as was the acyl-to-total ghrelin ratio. Most notably, leptin levels were significantly elevated in BBS patients.\n\nNormally, high leptin levels signal the brain to reduce appetite, and ghrelin should decrease after eating. In BBS patients, these negative feedback mechanisms appeared broken — ghrelin remained elevated despite adequate nutrition, and the body appeared resistant to leptin's appetite-suppressing effects. This shifts the hormonal balance toward constant hunger signaling.","whyItMatters":"Understanding why children with BBS develop severe obesity is critical for developing targeted treatments. This study provides evidence that the obesity isn't simply from overeating — it's driven by measurable hormonal imbalances in peptide signaling. This shifts the conversation from behavioral to biological and opens the door for potential peptide-based interventions like leptin sensitizers or ghrelin modulators.","specificNumbers":"","methodology":"The researchers measured five appetite-related hormones (total ghrelin, acylated ghrelin, obestatin, leptin, and adiponectin) in blood samples from eight children with BBS. Results were compared to healthy controls and analyzed in relation to body mass index and height. This was a case-control study design.","limitations":"The study included only 8 children with BBS, which is a very small sample size even for a rare disease. The cross-sectional design captures hormone levels at one point in time, not how they change over the course of disease. The study measured circulating hormone levels but did not directly assess receptor sensitivity or brain responses to these hormones."},{"rthcId":"RPEP-01913","title":"Thymosin-alpha 1 (Zadaxin) enhances the immunogenicity of an adjuvated pandemic H1N1v influenza vaccine (Focetria) in hemodialyzed patients: a pilot study.","authors":"Carraro, G; Naso, A; Montomoli, E; Gasparini, R; Camerini, R; Panatto, D; Tineo, M C; De Giorgi, L; Piccirella, S; Khadang, B; Ceracchi, M; De Rosa, A","year":2012,"journal":"Vaccine, 30(6), 1170-80","doi":"10.1016/j.vaccine.2011.12.014","pmid":"22178096","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01914","title":"Phospholipases and cationic peptides inhibit Cryptosporidium parvum sporozoite infectivity by parasiticidal and non-parasiticidal mechanisms.","authors":"Carryn, Stéphane; Schaefer, Deborah A; Imboden, Michael; Homan, E Jane; Bremel, Robert D; Riggs, Michael W","year":2012,"journal":"The Journal of parasitology, 98(1), 199-204","doi":"10.1645/GE-2822.1","pmid":"21787211","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01915","title":"Prevention of stress-impaired fear extinction through neuropeptide s action in the lateral amygdala.","authors":"Chauveau, Frédéric; Lange, Maren Denise; Jüngling, Kay; Lesting, Jörg; Seidenbecher, Thomas; Pape, Hans-Christian","year":2012,"journal":"Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 37(7), 1588-99","doi":"10.1038/npp.2012.3","pmid":"22298122","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01916","title":"Ghrelin and motilin in the gastrointestinal system.","authors":"Chen, Chih-Yen; Tsai, Chang-Youh","year":2012,"journal":"Current pharmaceutical design, 18(31), 4755-65","doi":null,"pmid":"22632857","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01917","title":"Difference in molecular pathology of natriuretic peptides in the myocardium between acute asphyxial and cardiac deaths.","authors":"Chen, Jian-Hua; Michiue, Tomomi; Ishikawa, Takaki; Maeda, Hitoshi","year":2012,"journal":"Legal medicine (Tokyo, Japan), 14(4), 177-82","doi":"10.1016/j.legalmed.2012.01.015","pmid":"22503242","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01918","title":"Effects of electroacupuncture of different frequencies on the release profile of endogenous opioid peptides in the central nerve system of goats.","authors":"Cheng, Li-Li; Ding, Ming-Xing; Xiong, Cheng; Zhou, Min-Yan; Qiu, Zheng-Ying; Wang, Qiong","year":2012,"journal":"Evidence-based complementary and alternative medicine : eCAM, 2012, 476457","doi":"10.1155/2012/476457","pmid":"23133494","tags":[],"studyType":"animal","evidenceStrength":"low","keyFinding":"Electroacupuncture at 60 Hz produced the strongest pain relief in goats, increasing pain threshold by 91%. This frequency uniquely triggered the simultaneous release of all three endogenous opioid peptides — met-enkephalin, β-endorphin, and dynorphin-A — across the broadest range of pain-related brain regions.\n\nLower frequencies (2 Hz) preferentially released met-enkephalin and β-endorphin, while high frequencies (80–100 Hz) favored dynorphin-A release. The 60 Hz frequency appeared to combine both patterns, activating more brain regions than any other frequency tested.","whyItMatters":"This study maps how different electrical stimulation frequencies trigger the release of the body's own pain-killing peptides in the central nervous system. Understanding which frequencies activate which opioid peptides could optimize acupuncture and neuromodulation protocols for pain management without synthetic drugs.","specificNumbers":"6 frequencies tested (0–100 Hz) · 30 min stimulation · 91% pain threshold increase at 60 Hz · 3 opioid peptides measured · p<0.05 across multiple brain regions","methodology":"Animal study in goats using electroacupuncture at six frequencies (0, 2, 40, 60, 80, 100 Hz) for 30 minutes. Pain threshold was measured using potassium iontophoresis. Endogenous opioid peptide levels (met-enkephalin, β-endorphin, dynorphin-A) were measured in multiple brain regions using SABC immunohistochemistry.","limitations":"This is an animal study in goats, and the findings may not directly translate to human pain physiology. The study required sacrificing animals to measure brain peptide levels, limiting its applicability to living subjects. Goat neuroanatomy differs from human anatomy, and the authors note species variation in responses."},{"rthcId":"RPEP-01919","title":"Carrageenan induced phosphorylation of Akt is dependent on neurokinin-1 expressing neurons in the superficial dorsal horn.","authors":"Choi, Jeong I L; Koehrn, Fred J; Sorkin, Linda S","year":2012,"journal":"Molecular pain, 8, 4","doi":"10.1186/1744-8069-8-4","pmid":"22243518","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01920","title":"Modulating social behavior with oxytocin: how does it work? What does it mean?","authors":"Churchland, Patricia S; Winkielman, Piotr","year":2012,"journal":"Hormones and behavior, 61(3), 392-9","doi":"10.1016/j.yhbeh.2011.12.003","pmid":"22197271","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01921","title":"The neuropeptide Y (NPY)-ergic system is associated with behavioral resilience to stress exposure in an animal model of post-traumatic stress disorder.","authors":"Cohen, Hagit; Liu, Tianmin; Kozlovsky, Nitsan; Kaplan, Zeev; Zohar, Joseph; Mathé, Aleksander A","year":2012,"journal":"Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 37(2), 350-63","doi":"10.1038/npp.2011.230","pmid":"21976046","tags":["neuropeptide-y"],"studyType":"animal-study","evidenceStrength":"moderate-preclinical","keyFinding":"Animals classified as having extremely disrupted behavior (EBR) after predator-scent stress showed significant downregulation of NPY in the hippocampus, periaqueductal gray, and amygdala compared to minimally disrupted (MBR), partially disrupted (PBR), and unexposed control animals.\n\nCritically, when NPY was administered centrally one hour after stress exposure, it significantly reduced the prevalence of extreme behavioral responses and decreased trauma-cue freezing behavior compared to vehicle controls. In contrast, an NPY-Y1-receptor antagonist did not provide protection, confirming the protective effect runs through NPY signaling.","whyItMatters":"PTSD remains difficult to treat, and not everyone exposed to trauma develops it — understanding what makes some individuals resilient is a major research priority. This study provides direct evidence that NPY levels in specific brain areas correlate with stress resilience, and that boosting NPY after trauma exposure can reduce the severity of PTSD-like symptoms. If these findings translate to humans, NPY-based therapies could potentially be given shortly after traumatic events to prevent PTSD from developing.","specificNumbers":"","methodology":"Sprague-Dawley rats were exposed to predator-scent stress for 15 minutes. Seven days later, behavior was assessed using elevated plus maze and acoustic startle response tests. Animals were classified by severity of behavioral disruption (extreme, partial, or minimal). NPY protein levels were measured in brain regions 8 days post-exposure. In a separate experiment, NPY agonist, NPY-Y1-receptor antagonist, or placebo was given centrally 1 hour after stress, and behavior was assessed the same way. Immunohistochemistry detected NPY, NPY-Y1 receptor, BDNF, and glucocorticoid receptor expression.","limitations":"This is an animal study using rats, so the findings may not directly translate to human PTSD. The predator-scent stress model, while established, doesn't capture the full complexity of human traumatic experiences. NPY was administered centrally (directly into the brain), which is not a practical delivery method for human patients. The study also did not examine long-term outcomes beyond the 8-day post-exposure window."},{"rthcId":"RPEP-01922","title":"Cyclotides as a basis for drug design.","authors":"Craik, David J; Swedberg, Joakim E; Mylne, Joshua S; Cemazar, Masa","year":2012,"journal":"Expert opinion on drug discovery, 7(3), 179-94","doi":"10.1517/17460441.2012.661554","pmid":"22468950","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01923","title":"Host-defense activities of cyclotides.","authors":"Craik, David J","year":2012,"journal":"Toxins, 4(2), 139-56","doi":"10.3390/toxins4020139","pmid":"22474571","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01924","title":"Thematic minireview series on circular proteins.","authors":"Craik, David J; Allewell, Norma M","year":2012,"journal":"The Journal of biological chemistry, 287(32), 26999-7000","doi":"10.1074/jbc.R112.390344","pmid":"22700978","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01925","title":"Mass Spectrometry-based Proteomics and Peptidomics for Systems Biology and Biomarker Discovery.","authors":"Cunningham, Robert; Ma, Di; Li, Lingjun","year":2012,"journal":"Frontiers in biology, 7(4), 313-335","doi":null,"pmid":"24504115","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01926","title":"Thymosin α 1: a novel therapeutic option for patients with refractory chronic purulent rhinosinusitis.","authors":"Dalm, Virgil A S H; de Wit, Harm; Drexhage, Hemmo A","year":2012,"journal":"Annals of the New York Academy of Sciences, 1270, 1-7","doi":"10.1111/j.1749-6632.2012.06742.x","pmid":"23050810","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Earlier studies demonstrated that patients with chronic purulent rhinosinusitis have disturbances in cell-mediated immunity and defective monocyte chemotaxis (the ability of immune cells to migrate toward infection sites). Treatment with thymostimulin, a thymic hormone preparation, led to significant clinical improvement and in vitro restoration of monocyte chemotaxis.\n\nWith thymostimulin no longer available, thymosin alpha-1 has emerged as a potential alternative that has demonstrated some benefit for CPR. Current research focuses on understanding thymosin alpha-1's effects on monocyte function and gene expression profiles to clarify its mechanisms of action before future clinical trials.","whyItMatters":"For the 5–10% of chronic sinus infection patients who don't respond to standard treatments including surgery, there are few options left. Understanding immune dysfunction as a root cause — and using immune-modulating peptides like thymosin alpha-1 to address it — represents a fundamentally different approach that targets the underlying problem rather than just managing symptoms.","specificNumbers":"","methodology":"This paper is a narrative review and research update combining findings from earlier clinical studies on thymostimulin in CPR patients with the authors' current in vitro laboratory work examining thymosin alpha-1's effects on monocyte function and gene expression. It is not a clinical trial or systematic review.","limitations":"This is primarily a narrative review and research update, not a clinical trial. The clinical evidence for thymosin alpha-1 in CPR is described as showing 'some benefit' but specifics are not detailed. The current work described is in vitro only. No clinical trial data for thymosin alpha-1 in CPR patients are presented in this paper."},{"rthcId":"RPEP-01927","title":"The use of ghrelin and ghrelin receptor agonists as a treatment for animal models of disease: efficacy and mechanism.","authors":"DeBoer, Mark D","year":2012,"journal":"Current pharmaceutical design, 18(31), 4779-99","doi":null,"pmid":"22632859","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01928","title":"Anti-obesity drugs: a review about their effects and their safety.","authors":"Derosa, Giuseppe; Maffioli, Pamela","year":2012,"journal":"Expert opinion on drug safety, 11(3), 459-71","doi":"10.1517/14740338.2012.675326","pmid":"22439841","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01929","title":"Growth hormone-releasing hormone receptor splice variant 1 is frequently expressed in oral squamous cell carcinomas.","authors":"Dioufa, Nikolina; Farmaki, Elena; Schally, Andrew V; Kiaris, Hippokratis; Vlahodimitropoulos, Dimitris; Papavassiliou, Athanasios G; Kittas, Christos; Block, Norman L; Chatzistamou, Ioulia","year":2012,"journal":"Hormones & cancer, 3(4), 172-80","doi":"10.1007/s12672-012-0108-8","pmid":"22441816","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"SV1 receptor immunoreactivity was detected in 44% (12 of 27) of oral squamous cell carcinomas compared to only 9% (3 of 33) of benign precancerous lesions (p<0.002). In cell culture, GHRH(1-29)NH2 and the GHRH agonist JI-38 stimulated HaCaT keratinocyte proliferation, and this growth stimulation was blocked by GHRH antagonists. The findings suggest SV1 expression may mark or contribute to malignant transformation in the oral epithelium.","whyItMatters":"Oral squamous cell carcinoma is a common and often aggressive cancer with limited targeted treatment options. Identifying SV1 as a receptor that appears during malignant transformation suggests a potential therapeutic target. Because GHRH antagonists are peptide-based and already in development for other cancers, this finding could accelerate new treatment approaches for oral cancer.","specificNumbers":"","methodology":"Researchers analyzed 33 benign precancerous oral lesions and 27 oral squamous cell carcinomas using immunohistochemistry for SV1 receptor expression. In parallel, they assessed SV1 expression in HaCaT keratinocytes by western blot and measured cell proliferation in response to GHRH agonists and antagonists via cell counting assays.","limitations":"The sample sizes are small (27 carcinomas, 33 precancerous lesions), limiting statistical power for subgroup analyses. The in vitro proliferation studies used HaCaT keratinocytes rather than actual oral cancer cell lines, which may behave differently. The study demonstrates correlation between SV1 expression and malignancy but cannot prove causation. No in vivo treatment data with GHRH antagonists were generated."},{"rthcId":"RPEP-01930","title":"Optimization of peptide-based ELISA for serological diagnostics: a retrospective study of human monkeypox infection.","authors":"Dubois, Melissa E; Hammarlund, Erika; Slifka, Mark K","year":2012,"journal":"Vector borne and zoonotic diseases (Larchmont, N.Y.), 12(5), 400-9","doi":"10.1089/vbz.2011.0779","pmid":"22217169","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01931","title":"Current and emerging concepts on the role of peripheral signals in the control of food intake and development of obesity.","authors":"Duca, F A; Covasa, M","year":2012,"journal":"The British journal of nutrition, 108(5), 778-93","doi":"10.1017/S0007114512000529","pmid":"22409929","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01932","title":"Low densities of serotonin and peptide YY cells in the colon of patients with irritable bowel syndrome.","authors":"El-Salhy, M; Gundersen, D; Ostgaard, H; Lomholt-Beck, B; Hatlebakk, J G; Hausken, T","year":2012,"journal":"Digestive diseases and sciences, 57(4), 873-8","doi":"10.1007/s10620-011-1948-8","pmid":"22057239","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01933","title":"Balancing ovulation and anovulation: integration of the reproductive and energy balance axes by neuropeptides.","authors":"Evans, J J; Anderson, G M","year":2012,"journal":"Human reproduction update, 18(3), 313-32","doi":"10.1093/humupd/dms004","pmid":"22442260","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01934","title":"The ghrelin gene products and exendin-4 promote survival of human pancreatic islet endothelial cells in hyperglycaemic conditions, through phosphoinositide 3-kinase/Akt, extracellular signal-related kinase (ERK)1/2 and cAMP/protein kinase A (PKA) signalling pathways.","authors":"Favaro, E; Granata, R; Miceli, I; Baragli, A; Settanni, F; Cavallo Perin, P; Ghigo, E; Camussi, G; Zanone, M M","year":2012,"journal":"Diabetologia, 55(4), 1058-70","doi":"10.1007/s00125-011-2423-y","pmid":"22231124","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01935","title":"Exogenous peptide YY3-36 and Exendin-4 further decrease food intake, whereas octreotide increases food intake in rats after Roux-en-Y gastric bypass.","authors":"Fenske, W K; Bueter, M; Miras, A D; Ghatei, M A; Bloom, S R; le Roux, C W","year":2012,"journal":"International journal of obesity (2005), 36(3), 379-84","doi":"10.1038/ijo.2011.126","pmid":"21694700","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01936","title":"Combined nuclear magnetic resonance spectroscopy and molecular dynamics study of growth hormone releasing hexapeptide GHRP-6 and a cyclic analogue.","authors":"Fernández-Oliva, Miguel; Santana, Héctor; Suardíaz, Reynier; Gavín, José A; Pérez, Carlos S","year":2012,"journal":"Magnetic resonance in chemistry : MRC, 50(5), 364-71","doi":"10.1002/mrc.3805","pmid":"22499151","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01937","title":"Cerebrolysin administration reduces oxidative stress-induced apoptosis in lymphocytes from healthy individuals.","authors":"Formichi, Patrizia; Radi, Elena; Battisti, Carla; Di Maio, Giuseppe; Muresanu, Dafin; Federico, Antonio","year":2012,"journal":"Journal of cellular and molecular medicine, 16(11), 2840-3","doi":"10.1111/j.1582-4934.2012.01615.x","pmid":"22882711","tags":["neuroprotective-peptides"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Cerebrolysin — a mixture of neurotrophic peptide fragments derived from pig brain proteins — significantly reduced oxidative stress-induced cell death (apoptosis) in human blood lymphocytes.\n\nWhen cells from 10 healthy individuals were exposed to a pro-apoptotic stimulus (2-deoxy-D-ribose, which causes oxidative stress), Cerebrolysin significantly reduced the number of cells undergoing programmed death. However, Cerebrolysin had no significant effect on cells cultured under normal, unstressed conditions — meaning it specifically protected against oxidative damage rather than broadly stimulating cell survival. The researchers proposed that peripheral blood lymphocytes could serve as a convenient cell model for studying Cerebrolysin's neuroprotective mechanisms.","whyItMatters":"Cerebrolysin is one of the few peptide-based drugs used clinically for neurological conditions (dementia and stroke recovery), particularly in Europe and Asia. Despite decades of clinical use, its molecular mechanisms remain poorly understood. This study adds evidence that Cerebrolysin's protective effects involve blocking oxidative stress-induced cell death — a process central to neurodegenerative diseases. Using blood cells as a proxy for neurons makes it easier to study these mechanisms.","specificNumbers":"n=10 healthy donors · Significant reduction in apoptotic cells after oxidative stress · No effect under standard culture conditions · Flow cytometry + fluorescence microscopy analysis","methodology":"Peripheral blood lymphocytes from 10 healthy adults were cultured and exposed to 2-deoxy-D-ribose (dRib), a reducing sugar that induces oxidative stress and apoptosis. Cerebrolysin was added at various concentrations. Apoptosis was measured using flow cytometry and fluorescence microscopy. Cells were also cultured under standard conditions with Cerebrolysin to test baseline effects.","limitations":"This was an in vitro study using blood lymphocytes, not neurons — the relevance to actual brain cell protection is indirect. Only 10 donors were tested. The study used a chemical oxidative stressor rather than disease-relevant neurodegeneration models. The specific peptide components in Cerebrolysin responsible for the protective effect were not identified."},{"rthcId":"RPEP-01938","title":"Reduction of ultraviolet light-induced DNA damage in human colon cancer cells treated with a lactoferrin-derived peptide.","authors":"Freiburghaus, C; Lindmark-Månsson, H; Paulsson, M; Oredsson, S","year":2012,"journal":"Journal of dairy science, 95(10), 5552-60","doi":"10.3168/jds.2011-5279","pmid":"22901475","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01939","title":"Peripheral and central mechanisms involved in the control of food intake by dietary amino acids and proteins.","authors":"Fromentin, Gilles; Darcel, Nicolas; Chaumontet, Catherine; Marsset-Baglieri, Agnes; Nadkarni, Nachiket; Tomé, Daniel","year":2012,"journal":"Nutrition research reviews, 25(1), 29-39","doi":"10.1017/S0954422411000175","pmid":"22643031","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01940","title":"Bovine lactoferrin digested with human gastrointestinal enzymes inhibits replication of human echovirus 5 in cell culture.","authors":"Furlund, Camilla B; Kristoffersen, Anja B; Devold, Tove G; Vegarud, Gerd E; Jonassen, Christine M","year":2012,"journal":"Nutrition research (New York, N.Y.), 32(7), 503-13","doi":"10.1016/j.nutres.2012.06.006","pmid":"22901558","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01941","title":"Heart failure outcomes and benefits of NT-proBNP-guided management in the elderly: results from the prospective, randomized ProBNP outpatient tailored chronic heart failure therapy (PROTECT) study.","authors":"Gaggin, Hanna K; Mohammed, Asim A; Bhardwaj, Anju; Rehman, Shafiq U; Gregory, Shawn A; Weiner, Rory B; Baggish, Aaron L; Moore, Stephanie A; Semigran, Marc J; Januzzi, James L","year":2012,"journal":"Journal of cardiac failure, 18(8), 626-34","doi":"10.1016/j.cardfail.2012.05.005","pmid":"22858078","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01942","title":"A customized self-assembling peptide hydrogel for dental pulp tissue engineering.","authors":"Galler, Kerstin M; Hartgerink, Jeffrey D; Cavender, Adriana C; Schmalz, Gottfried; D'Souza, Rena N","year":2012,"journal":"Tissue engineering. Part A, 18(1-2), 176-84","doi":"10.1089/ten.TEA.2011.0222","pmid":"21827280","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01943","title":"PET imaging of angiogenesis after myocardial infarction/reperfusion using a one-step labeled integrin-targeted tracer 18F-AlF-NOTA-PRGD2.","authors":"Gao, Haokao; Lang, Lixin; Guo, Ning; Cao, Feng; Quan, Qimeng; Hu, Shuo; Kiesewetter, Dale O; Niu, Gang; Chen, Xiaoyuan","year":2012,"journal":"European journal of nuclear medicine and molecular imaging, 39(4), 683-92","doi":"10.1007/s00259-011-2052-1","pmid":"22274731","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01944","title":"Thymosin α1 and cancer: action on immune effector and tumor target cells.","authors":"Garaci, Enrico; Pica, Francesca; Serafino, Annalucia; Balestrieri, Emanuela; Matteucci, Claudia; Moroni, Gabriella; Sorrentino, Roberta; Zonfrillo, Manuela; Pierimarchi, Pasquale; Sinibaldi-Vallebona, Paola","year":2012,"journal":"Annals of the New York Academy of Sciences, 1269, 26-33","doi":"10.1111/j.1749-6632.2012.06697.x","pmid":"23045967","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01945","title":"Clinical characteristics and outcome of acromegaly induced by ectopic secretion of growth hormone-releasing hormone (GHRH): a French nationwide series of 21 cases.","authors":"Garby, Laetitia; Caron, Philippe; Claustrat, Francine; Chanson, Philippe; Tabarin, Antoine; Rohmer, Vincent; Arnault, Gwenaëlle; Bonnet, Fabrice; Chabre, Olivier; Christin-Maitre, Sophie; du-Boullay, Hélène; Murat, Arnaud; Nakib, Ihab; Sadoul, Jean-Louis; Sassolas, Geneviève; Claustrat, Bruno; Raverot, Gérald; Borson-Chazot, Françoise","year":2012,"journal":"The Journal of clinical endocrinology and metabolism, 97(6), 2093-104","doi":"10.1210/jc.2011-2930","pmid":"22442262","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01946","title":"Validation of Ussing chamber technology to study satiety hormone release from human duodenal specimens.","authors":"Geraedts, Maartje C P; Troost, Freddy J; De Ridder, Rogier J; Bodelier, Alexander G L; Masclee, Ad A M; Saris, Wim H M","year":2012,"journal":"Obesity (Silver Spring, Md.), 20(3), 678-82","doi":"10.1038/oby.2011.104","pmid":"21566565","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01947","title":"Development and validation of a bioanalytical LC-MS method for the quantification of GHRP-6 in human plasma.","authors":"Gil, Jeovanis; Cabrales, Ania; Reyes, Osvaldo; Morera, Vivian; Betancourt, Lázaro; Sánchez, Aniel; García, Gerardo; Moya, Galina; Padrón, Gabriel; Besada, Vladimir; González, Luis Javier","year":2012,"journal":"Journal of pharmaceutical and biomedical analysis, 60, 19-25","doi":"10.1016/j.jpba.2011.11.007","pmid":"22154075","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01948","title":"Neuropeptide modulation of central amygdala neuroplasticity is a key mediator of alcohol dependence.","authors":"Gilpin, Nicholas W; Roberto, Marisa","year":2012,"journal":"Neuroscience and biobehavioral reviews, 36(2), 873-88","doi":"10.1016/j.neubiorev.2011.11.002","pmid":"22101113","tags":["neuropeptides","alcohol-dependence"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"The central amygdala (CeA) is a critical brain region where neuropeptides modulate alcohol dependence. Acute alcohol suppresses excitatory glutamate transmission and enhances inhibitory GABA transmission in the CeA. Chronic alcohol exposure flips this pattern — glutamate transmission increases while GABA transmission also rises.\n\nPro-anxiety neuropeptides like CRF (corticotropin-releasing factor) and dynorphin increase GABAergic (inhibitory) signaling in the CeA, while anti-anxiety peptides like NPY (neuropeptide Y) and nociceptin decrease it. These peptides also modulate how alcohol affects CeA neurons — some enhance alcohol's effects, others block them.\n\nChronic alcohol produces lasting changes in these neuropeptide systems, which may drive the transition from casual drinking to dependence through negative reinforcement — drinking to avoid withdrawal-related anxiety rather than for pleasure.","whyItMatters":"This review maps out how multiple neuropeptide systems in the brain's fear and anxiety center work together to drive alcohol dependence. Understanding these mechanisms could lead to new treatments that target specific peptide pathways to reduce cravings and withdrawal symptoms, moving beyond current one-size-fits-all approaches to alcohol use disorder.","specificNumbers":"","methodology":"This is a review paper that synthesizes electrophysiology research examining how six neuropeptide/neuromodulator systems (CRF, NPY, nociceptin, dynorphin, endocannabinoids, and galanin) affect inhibitory neurotransmission in the central amygdala, and how acute and chronic alcohol exposure interacts with these systems.","limitations":"As a review, this paper synthesizes existing research rather than presenting new experimental data. Much of the underlying evidence comes from animal models, so direct translation to human alcohol dependence requires caution. The complexity of neuropeptide interactions means individual findings may not capture the full picture of how these systems work together in vivo."},{"rthcId":"RPEP-01949","title":"Neuropeptide Y (NPY) in the extended amygdala is recruited during the transition to alcohol dependence.","authors":"Gilpin, Nicholas W","year":2012,"journal":"Neuropeptides, 46(6), 253-9","doi":"10.1016/j.npep.2012.08.001","pmid":"22938859","tags":["neuropeptides","addiction"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Neuropeptide Y (NPY) in the central amygdala (CeA) plays a critical role in the transition to alcohol dependence. Mice lacking the NPY gene show both high anxiety and high alcohol drinking. Rats bred to prefer alcohol have baseline NPY deficits in the CeA, and infusing NPY into the CeA suppresses excessive drinking in both alcohol-preferring and alcohol-dependent rats. The author proposes that NPY modulates anxiety via Y2 receptor regulation of NPY release, while it reduces alcohol drinking via Y2 receptor regulation of GABA release — two distinct mechanisms through the same receptor.","whyItMatters":"Alcohol dependence involves a vicious cycle: withdrawal causes anxiety, which drives more drinking. NPY appears to be a natural brake on both anxiety and alcohol consumption, and this brake is weakened in dependent animals. Understanding this peptide pathway could lead to targeted treatments that address the biological root of alcohol dependence rather than just managing symptoms.","specificNumbers":"NPY gene deletion → high anxiety + high drinking phenotype · CeA-localized effects · Y2 receptor dual mechanism (NPY release for anxiety, GABA release for drinking)","methodology":"Narrative review synthesizing findings from multiple rodent studies including gene knockout models, selective breeding experiments, and direct brain infusion studies. Proposes a mechanistic hypothesis for NPY's dual role in anxiety and alcohol dependence via Y2 receptor signaling.","limitations":"Review of animal studies — findings may not directly translate to human alcohol dependence. The proposed dual Y2 receptor mechanism is a hypothesis requiring further experimental validation. Brain infusion of NPY is not a feasible clinical treatment approach. Human NPY genetics and alcohol dependence relationships are more complex than rodent models suggest."},{"rthcId":"RPEP-01950","title":"CCK-8 and CCK-58 differ in their effects on nocturnal solid meal pattern in undisturbed rats.","authors":"Goebel-Stengel, Miriam; Stengel, Andreas; Wang, Lixin; Ohning, Gordon; Taché, Yvette; Reeve, Joseph R","year":2012,"journal":"American journal of physiology. Regulatory, integrative and comparative physiology, 303(8), R850-60","doi":"10.1152/ajpregu.00365.2011","pmid":"22874423","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01951","title":"Effect of Gly-Gly-His, Gly-His-Lys and their copper complexes on TNF-alpha-dependent IL-6 secretion in normal human dermal fibroblasts.","authors":"Gruchlik, Arkadiusz; Jurzak, Magdalena; Chodurek, Ewa; Dzierzewicz, Zofia","year":2012,"journal":"Acta poloniae pharmaceutica, 69(6), 1303-6","doi":null,"pmid":"23285694","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01952","title":"Effects of intranasal oxytocin on social anxiety in males with fragile X syndrome.","authors":"Hall, Scott S; Lightbody, Amy A; McCarthy, Brigid E; Parker, Karen J; Reiss, Allan L","year":2012,"journal":"Psychoneuroendocrinology, 37(4), 509-18","doi":"10.1016/j.psyneuen.2011.07.020","pmid":"21862226","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In this randomized double-blind placebo-controlled single-dose trial with 8 males with Fragile X syndrome, intranasal oxytocin showed dose-dependent effects on different anxiety measures during a structured social challenge conducted 50 minutes after administration.\n\nThe 24 IU dose significantly improved eye gaze frequency — a key behavioral marker of social engagement that is severely impaired in Fragile X. The 48 IU dose significantly decreased salivary cortisol levels, indicating reduced physiological stress response. No significant effects were observed on heart rate, respiratory sinus arrhythmia (RSA), or heart rate variability (HRV), though individual heart rate data showed bidirectional responses (some participants increased, others decreased), suggesting oxytocin's effects may be individually variable.","whyItMatters":"Fragile X syndrome is the most common inherited cause of intellectual disability, and social anxiety is one of its most disabling features. Current treatments are limited and often involve sedating medications. Oxytocin's ability to improve social engagement (eye contact) and reduce stress hormones in this population — even in a single dose — suggests a fundamentally different therapeutic approach that works with the brain's natural social bonding system rather than simply sedating anxiety.","specificNumbers":"","methodology":"Randomized double-blind placebo-controlled single-dose trial at Stanford University. Ten low-functioning males with Fragile X syndrome (aged 13-28 years) were enrolled; 8 completed the study. Each participant received intranasal placebo, 24 IU oxytocin, and 48 IU oxytocin in a crossover design. Fifty minutes after administration, participants underwent a structured social challenge. Outcome measures included eye gaze frequency (behavioral), heart rate, RSA, HRV (autonomic), and salivary cortisol (endocrine stress marker).","limitations":"The sample size of 8 completers is very small, limiting statistical power and generalizability. This was a single-dose study, so chronic dosing effects are unknown. Only males were studied; females with Fragile X are generally less severely affected and may respond differently. The heart rate variability results were inconsistent across participants. The 50-minute time window may not capture the full duration of oxytocin's effects. The structured social challenge may not represent real-world social situations."},{"rthcId":"RPEP-01953","title":"Effect of teriparatide on bone mineral density and fracture in postmenopausal osteoporosis: meta-analysis of randomised controlled trials.","authors":"Han, S-L; Wan, S-L","year":2012,"journal":"International journal of clinical practice, 66(2), 199-209","doi":"10.1111/j.1742-1241.2011.02837.x","pmid":"22257045","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Teriparatide increased spine bone mineral density by 8.14% and hip BMD by 2.48% in postmenopausal women with osteoporosis. It reduced vertebral fracture risk by 70% (risk ratio 0.30) and non-vertebral fracture risk by 38% (risk ratio 0.62). Women who took more than 1,500 mg of calcium daily had significantly greater hip BMD gains (3.72% vs. 1.40%, p=0.004). Longer treatment duration did not appear to produce additional benefits.","whyItMatters":"Osteoporosis fractures cause enormous suffering and healthcare costs in postmenopausal women. This meta-analysis pooled data from 8 randomized controlled trials to confirm that teriparatide — a peptide fragment of parathyroid hormone — is highly effective at building bone and preventing fractures. The finding about calcium intake is practically important: adequate calcium supplementation significantly amplifies teriparatide's effect on hip bone density.","specificNumbers":"","methodology":"The researchers searched electronic databases and reference lists, identifying 8 randomized controlled trials with a combined 2,388 postmenopausal women with osteoporosis. All trials evaluated daily subcutaneous teriparatide injections. Data were pooled using a random-effects model, measuring percentage change in bone mineral density and fracture risk ratios.","limitations":"Only 3 of the 8 trials reported fracture outcomes, limiting the fracture risk analysis. The meta-analysis included trials of varying duration and calcium supplementation protocols. Publication bias is possible. The analysis could not fully control for differences in study populations across trials."},{"rthcId":"RPEP-01954","title":"Structural and biophysical characterization of an antimicrobial peptide chimera comprised of lactoferricin and lactoferrampin.","authors":"Haney, Evan F; Nazmi, Kamran; Bolscher, Jan G M; Vogel, Hans J","year":2012,"journal":"Biochimica et biophysica acta, 1818(3), 762-75","doi":"10.1016/j.bbamem.2011.11.023","pmid":"22155682","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01955","title":"Cerebrolysin in patients with acute ischemic stroke in Asia: results of a double-blind, placebo-controlled randomized trial.","authors":"Heiss, Wolf-Dieter; Brainin, Michael; Bornstein, Natan M; Tuomilehto, Jaakko; Hong, Zhen","year":2012,"journal":"Stroke, 43(3), 630-6","doi":"10.1161/STROKEAHA.111.628537","pmid":"22282884","tags":["neuroscience-and-neuropeptides"],"studyType":"randomized-controlled-trial","evidenceStrength":"moderate","keyFinding":"In this large double-blind, placebo-controlled trial of 1,070 patients with acute ischemic stroke in Asia, Cerebrolysin (30 mL daily IV for 10 days) failed to meet its primary endpoint — there was no significant difference between Cerebrolysin and placebo on a combined measure of stroke recovery scales.\n\nHowever, a post hoc subgroup analysis of severely affected patients (NIHSS >12) showed a favorable trend: the Cerebrolysin group had better scores on both the NIHSS (OR 1.27) and modified Rankin Scale (OR 1.27). Most strikingly, 90-day mortality in this severe subgroup was 10.5% with Cerebrolysin versus 20.2% with placebo (hazard ratio 1.97, CI lower bound 1.00).","whyItMatters":"Acute ischemic stroke remains devastating, and effective neuroprotective treatments beyond clot removal are limited. While Cerebrolysin didn't help the overall stroke population in this trial, the signal in severely affected patients — particularly the halved mortality rate — suggests the peptide mixture may have a role specifically in the most serious strokes, where brain damage is extensive and neuroprotection matters most.","specificNumbers":"n=1,070 · 529 Cerebrolysin, 541 placebo · 30 mL IV daily × 10 days · Primary endpoint: neutral · Severe subgroup (NIHSS >12): 10.5% vs 20.2% mortality at 90 days · OR 1.27 for NIHSS improvement in severe subgroup","methodology":"Double-blind, placebo-controlled randomized clinical trial across Asian centers. Patients with acute ischemic hemispheric stroke were randomized within 12 hours of symptom onset to receive either Cerebrolysin 30 mL daily or saline placebo as IV infusion for 10 days, plus aspirin 100 mg daily. Follow-up was 90 days. Primary endpoint was a combined global test of modified Rankin Scale, Barthel Index, and NIHSS.","limitations":"The primary endpoint was negative — Cerebrolysin did not outperform placebo in the overall population. The favorable findings in severe stroke patients came from a post hoc subgroup analysis, which is hypothesis-generating, not confirmatory. Treatment was given within 12 hours of onset, which may miss the earliest therapeutic window. The study was conducted only in Asian populations."},{"rthcId":"RPEP-01956","title":"GLP-1 analog liraglutide protects against oxidative stress and albuminuria in streptozotocin-induced diabetic rats via protein kinase A-mediated inhibition of renal NAD(P)H oxidases.","authors":"Hendarto, Hari; Inoguchi, Toyoshi; Maeda, Yasutaka; Ikeda, Noriko; Zheng, Jing; Takei, Ryoko; Yokomizo, Hisashi; Hirata, Eiichi; Sonoda, Noriyuki; Takayanagi, Ryoichi","year":2012,"journal":"Metabolism: clinical and experimental, 61(10), 1422-34","doi":"10.1016/j.metabol.2012.03.002","pmid":"22554832","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01957","title":"Ghrelin and growth hormone secretagogue receptor (GHSR) genes are not commonly involved in growth or weight abnormalities in an Israeli pediatric population.","authors":"Hess, Ora; Admoni, Osnat; Khayat, Morad; Elias, Gadir; Almagor, Tal; Shalev, Stavit-Allon; Tenenbaum-Rakover, Yardena","year":2012,"journal":"Journal of pediatric endocrinology & metabolism : JPEM, 25(5-6), 537-40","doi":null,"pmid":"22876551","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 98 children with growth or weight abnormalities, seven different sequence changes were identified in GHSR (two novel, five previously described), but none affected the protein-coding region. The ghrelin gene variant p.L72M was found in five patients but occurred at a higher rate in healthy controls, arguing against a pathogenic role.\n\nDespite a high overall rate of sequence variations in both ghrelin and GHSR, none of the changes were functionally significant, indicating that mutations in these genes are not a common explanation for short stature, failure to thrive, growth hormone deficiency, or obesity in this population.","whyItMatters":"Understanding the genetic basis of growth and weight disorders in children is crucial for developing targeted treatments. While ghrelin is a major regulator of appetite and growth, this study demonstrates that simply looking for mutations in the ghrelin system is not a productive diagnostic strategy for most children with these conditions. This redirects attention toward other genetic and environmental factors and highlights the complexity of growth regulation beyond single-gene explanations.","specificNumbers":"","methodology":"Ninety-eight children (38 female, 60 male) from an Israeli population were enrolled across four diagnostic groups: failure to thrive (n=9), growth hormone deficiency (n=44), idiopathic short stature (n=22), and obesity (n=23). The coding exons of both the ghrelin and GHSR genes were screened for mutations by direct DNA sequencing. Identified variants were compared against previously reported mutations and control population frequencies.","limitations":"The sample size of 98 is relatively small for a genetic screening study, limiting power to detect rare pathogenic variants. The study only sequenced coding exons, so regulatory mutations or deep intronic variants could have been missed. The population was from a single Israeli center, so results may not apply to other ethnic groups. Functional studies of the identified variants were not performed."},{"rthcId":"RPEP-01958","title":"Ghrelin is involved in voluntary anorexia in Atlantic salmon raised at elevated sea temperatures.","authors":"Hevrøy, E M; Waagbø, R; Torstensen, B E; Takle, H; Stubhaug, I; Jørgensen, S M; Torgersen, T; Tvenning, L; Susort, S; Breck, O; Hansen, T","year":2012,"journal":"General and comparative endocrinology, 175(1), 118-34","doi":"10.1016/j.ygcen.2011.10.007","pmid":"22036890","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01959","title":"Social memory, amnesia, and autism: brain oxytocin secretion is regulated by NAD+ metabolites and single nucleotide polymorphisms of CD38.","authors":"Higashida, Haruhiro; Yokoyama, Shigeru; Huang, Jian-Jun; Liu, Li; Ma, Wen-Jie; Akther, Shirin; Higashida, Chiharu; Kikuchi, Mitsuru; Minabe, Yoshio; Munesue, Toshio","year":2012,"journal":"Neurochemistry international, 61(6), 828-38","doi":"10.1016/j.neuint.2012.01.030","pmid":"22366648","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01960","title":"Fuel selection and appetite-regulating hormones after intake of a soy protein-based meal replacement.","authors":"König, Daniel; Muser, Klaus; Berg, Aloys; Deibert, Peter","year":2012,"journal":"Nutrition (Burbank, Los Angeles County, Calif.), 28(1), 35-9","doi":"10.1016/j.nut.2011.02.008","pmid":"21778035","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Compared to a standard high-glycemic/low-protein breakfast, the soy protein meal replacement produced:\n\n- Considerably lower glucose and insulin responses after eating\n- Significantly less suppression of fat oxidation in the postprandial period — meaning the body kept burning fat rather than switching entirely to carbohydrate burning\n- A 'second meal effect' where higher fat oxidation persisted even after a standardized lunch eaten 4 hours later\n- Significantly lower ghrelin levels at 2 hours post-meal\n- A trend toward higher PYY (peptide YY) levels, suggesting increased satiety signaling\n\nThese combined effects — lower insulin, more fat burning, reduced hunger hormone, and increased fullness signaling — provide a mechanistic explanation for why high-protein, low-glycemic meal replacements may help with weight management.","whyItMatters":"This study connects two important areas of peptide research — appetite-regulating gut hormones (ghrelin and PYY) and metabolic fuel selection. It demonstrates that what you eat doesn't just affect blood sugar; it changes the hormonal signals that control hunger and satiety. For people with metabolic syndrome, these effects are especially relevant because their insulin resistance already disrupts normal appetite regulation and fat metabolism.","specificNumbers":"","methodology":"Randomized crossover study in 11 overweight or obese men with metabolic syndrome and insulin resistance. Each subject consumed either 65g of a soy protein meal replacement (high protein, low glycemic index) or an isocaloric standardized breakfast (high glycemic index, low protein) on separate mornings. Four hours later, all ate the same standardized lunch. Researchers measured blood glucose, insulin, ghrelin, PYY, oxygen uptake, and CO2 production. Respiratory quotient and substrate utilization (fat vs. carbohydrate burning) were calculated from gas exchange data.","limitations":"Very small sample size (n=11) with only male participants, all with metabolic syndrome — findings may not apply to women, normal-weight individuals, or those without insulin resistance. This was a single-dose acute study; long-term effects of repeated meal replacement use were not assessed. The soy meal replacement differed from the standard breakfast in both protein content and glycemic index, making it impossible to determine which factor drove the hormone and metabolic changes. PYY results only showed a trend, not statistical significance."},{"rthcId":"RPEP-01961","title":"Lactoferricin B inhibits the phosphorylation of the two-component system response regulators BasR and CreB.","authors":"Ho, Yu-Hsuan; Sung, Tzu-Cheng; Chen, Chien-Sheng","year":2012,"journal":"Molecular & cellular proteomics : MCP, 11(4), M111.014720","doi":"10.1074/mcp.M111.014720","pmid":"22138548","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01962","title":"Chimeric relaxin peptides highlight the role of the A-chain in the function of H2 relaxin.","authors":"Hossain, Mohammed Akhter; Wade, John D; Bathgate, Ross A D","year":2012,"journal":"Peptides, 35(1), 102-6","doi":"10.1016/j.peptides.2012.02.021","pmid":"22414484","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01963","title":"Visceral hypersensitivity in symptomatic diverticular disease and the role of neuropeptides and low grade inflammation.","authors":"Humes, D J; Simpson, J; Smith, J; Sutton, P; Zaitoun, A; Bush, D; Bennett, A; Scholefield, J H; Spiller, R C","year":2012,"journal":"Neurogastroenterology and motility, 24(4), 318-e163","doi":"10.1111/j.1365-2982.2011.01863.x","pmid":"22276853","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01964","title":"An amyloidogenic determinant in N-terminal pro-brain natriuretic peptide (NT-proBNP): Implications for cardiac amyloidoses.","authors":"Iconomidou, Vassiliki A; Pheida, Danae; Hamodraka, Eftihia S; Antony, Claude; Hoenger, Andreas; Hamodrakas, Stavros J","year":2012,"journal":"Biopolymers, 98(1), 67-75","doi":"10.1002/bip.21698","pmid":"21792845","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01965","title":"Dosing rationale for liraglutide in type 2 diabetes mellitus: a pharmacometric assessment.","authors":"Ingwersen, Steen H; Khurana, Manoj; Madabushi, Rajanikanth; Watson, Estelle; Jonker, Daniël M; Le Thi, Tu Duyen; Jacobsen, Lisbeth V; Tornøe, Christoffer W","year":2012,"journal":"Journal of clinical pharmacology, 52(12), 1815-23","doi":"10.1177/0091270011430504","pmid":"22174428","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01966","title":"Estimating glomerular filtration rate from serum creatinine and cystatin C.","authors":"Inker, Lesley A; Schmid, Christopher H; Tighiouart, Hocine; Eckfeldt, John H; Feldman, Harold I; Greene, Tom; Kusek, John W; Manzi, Jane; Van Lente, Frederick; Zhang, Yaping Lucy; Coresh, Josef; Levey, Andrew S","year":2012,"journal":"The New England journal of medicine, 367(1), 20-9","doi":"10.1056/NEJMoa1114248","pmid":"22762315","tags":["biomarkers","kidney"],"studyType":"observational","evidenceStrength":"strong","keyFinding":"Combining cystatin C (a small peptide biomarker) with creatinine to estimate kidney filtration rate (GFR) is significantly more accurate than using either marker alone. The combined equation reduced errors by about a third — only 8.5% of estimates were off by more than 30%, compared to 12.8% for creatinine alone and 14.1% for cystatin C alone (both P<0.001).\n\nCritically, for patients in the diagnostic gray zone (estimated GFR 45–74), the combined equation correctly reclassified 16.9% of those who appeared to have chronic kidney disease back to normal kidney function — preventing unnecessary diagnoses and treatments.","whyItMatters":"Chronic kidney disease (CKD) diagnosis relies on estimating how well your kidneys filter blood. The standard creatinine-based test is imprecise and can falsely diagnose CKD in many patients. By adding cystatin C — a peptide freely filtered by the kidney — doctors can get a much more accurate picture of kidney function, preventing overdiagnosis and ensuring that patients who truly have CKD get identified and treated earlier.","specificNumbers":"n=5,352 (development) · n=1,119 (validation) · 13 + 5 studies · Combined equation error >30%: 8.5% vs 12.8% (creatinine) vs 14.1% (cystatin C) · Net reclassification: 19.4% · 16.9% correctly reclassified as normal","methodology":"Cross-sectional study developing and validating GFR estimation equations. Development used 5,352 participants from 13 studies; validation used 1,119 participants from 5 different studies where GFR was directly measured. Three equations were compared: creatinine-based, cystatin C-based, and combined creatinine-cystatin C. All assays were traceable to primary reference materials.","limitations":"Cross-sectional design cannot track changes in kidney function over time. The equations were developed from specific populations and may perform differently in underrepresented groups. Cystatin C levels can be affected by factors other than kidney function (inflammation, thyroid disease, corticosteroid use), which could introduce errors in certain patients."},{"rthcId":"RPEP-01967","title":"Gonadotropins","authors":"Irani, Mohamad; Merhi, Zaher","year":2012,"journal":"Fertility and sterility, 102(2), 460-468.e3","doi":"10.1016/j.fertnstert.2014.04.046","pmid":"31644163","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01968","title":"Human cathelicidin LL-37 prevents bacterial biofilm formation.","authors":"Jacobsen, Andreas S; Jenssen, Håvard","year":2012,"journal":"Future medicinal chemistry, 4(12), 1587-99","doi":"10.4155/fmc.12.97","pmid":"22917247","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01969","title":"Beneficial effects of novel antagonists of GHRH in different models of Alzheimer's disease.","authors":"Jaszberenyi, Miklos; Rick, Ferenc G; Szalontay, Luca; Block, Norman L; Zarandi, Marta; Cai, Ren-Zhi; Schally, Andrew V","year":2012,"journal":"Aging, 4(11), 755-67","doi":null,"pmid":"23211425","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01970","title":"Effect of the neuroprotective peptide davunetide (AL-108) on cognition and functional capacity in schizophrenia.","authors":"Javitt, Daniel C; Buchanan, Robert W; Keefe, Richard S E; Kern, Robert; McMahon, Robert P; Green, Michael F; Lieberman, Jeffrey; Goff, Donald C; Csernansky, John G; McEvoy, Joseph P; Jarskog, Fred; Seidman, Larry J; Gold, James M; Kimhy, David; Nolan, Karen S; Barch, Deanna S; Ball, M Patricia; Robinson, James; Marder, Stephen R","year":2012,"journal":"Schizophrenia research, 136(1-3), 25-31","doi":"10.1016/j.schres.2011.11.001","pmid":"22169248","tags":["neuroprotection","cognitive-enhancement"],"studyType":"randomized-controlled-trial","evidenceStrength":"moderate","keyFinding":"Intranasal davunetide (NAP peptide) did not significantly improve cognitive test scores (MCCB) versus placebo in 63 people with schizophrenia over 12 weeks. However, it did significantly improve functional capacity — the ability to perform real-world tasks — as measured by the UPSA (p = 0.048).\n\nThe 5 mg dose showed stronger effects than 30 mg, with effect sizes of d = 0.74 for functional capacity and d = 0.34 for cognition. The peptide was well tolerated with no significant side effects. The authors estimated 45–50 subjects per group would be needed to detect significant cognitive effects in future trials.","whyItMatters":"Cognitive dysfunction is the biggest predictor of disability in schizophrenia, yet no approved drugs effectively treat it. Antipsychotics control hallucinations and delusions but do almost nothing for thinking problems. Davunetide's improvement of functional capacity — even without clear cognitive test score improvements — is intriguing because real-world functioning is ultimately what matters most for patients. The dissociation between test scores and functional outcomes raises important questions about how we measure cognitive benefit.","specificNumbers":"n=63 · 3 arms (5 mg, 30 mg, placebo) · 12 weeks · MCCB cognition: p = 0.45 (not significant) · UPSA functional capacity: p = 0.048 (significant) · effect sizes: d = 0.74 (5 mg UPSA), d = 0.48 (30 mg UPSA), d = 0.34 (5 mg MCCB) · 0 significant adverse events","methodology":"Multicenter, double-blind, parallel-group randomized clinical trial. 63 adults with schizophrenia were assigned to intranasal davunetide at 5 mg, 30 mg, or placebo for 12 weeks while continuing their current antipsychotic medications. Cognition was assessed using the MATRICS battery (MCCB), and functional capacity using UPSA and SCoRS scales.","limitations":"Small sample size (n=63 across three arms, ~21 per group) — underpowered to detect moderate cognitive effects. The primary cognitive measure (MCCB) was not significant. Only 12 weeks of treatment — longer durations might show different results. The significant UPSA finding could be a chance result given the small sample and multiple comparisons. Davunetide was later discontinued for progressive supranuclear palsy, which may have dampened enthusiasm for schizophrenia development."},{"rthcId":"RPEP-01971","title":"Teduglutide, a novel glucagon-like peptide 2 analog, in the treatment of patients with short bowel syndrome.","authors":"Jeppesen, Palle Bekker","year":2012,"journal":"Therapeutic advances in gastroenterology, 5(3), 159-71","doi":"10.1177/1756283X11436318","pmid":"22570676","tags":["GLP-2","short-bowel-syndrome"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Teduglutide, a GLP-2 analog, promotes intestinal mucosal growth and restores absorptive function in patients with short bowel syndrome (SBS), reducing their dependence on intravenous parenteral nutrition (PN). In a Phase II study, teduglutide reduced diarrhea by approximately 700 g/day and fecal energy losses by about 0.8 MJ/day over 3 weeks. Two Phase III randomized placebo-controlled 24-week trials confirmed these results, showing significant improvements in intestinal fluid absorption.\n\nThe drug works by enhancing the structural and functional integrity of remaining intestine — essentially making the surviving gut more efficient at absorbing nutrients and fluid. This translated to measurable reductions in the volume and frequency of parenteral support needed, significantly improving patients' quality of life.","whyItMatters":"Short bowel syndrome patients who can't absorb enough nutrients depend on IV nutrition (parenteral support) delivered through a central line — a lifesaving but burdensome treatment that carries risks of bloodstream infections, blood clots, and liver disease. Teduglutide is the first drug to address the root problem by regenerating intestinal tissue and improving absorption, potentially freeing patients from some or all of their IV nutrition dependence.","specificNumbers":"~700 g/day diarrhea reduction · ~0.8 MJ/day fecal energy loss reduction · 24-week Phase III trials · 2 randomized placebo-controlled trials · up to 24 weeks safety data","methodology":"Review covering teduglutide's mechanism of action, Phase II metabolic balance study results, and two Phase III randomized, placebo-controlled, 24-week clinical trials in patients with short bowel syndrome and intestinal failure.","limitations":"Studies covered up to 24 weeks in duration — long-term safety and efficacy data (years of treatment) were not yet available at time of publication. The review was published before FDA approval, so post-marketing safety data is not included. Teduglutide promotes mucosal growth, raising theoretical concerns about intestinal polyps that require ongoing monitoring."},{"rthcId":"RPEP-01972","title":"Stapled BH3 peptides against MCL-1: mechanism and design using atomistic simulations.","authors":"Joseph, Thomas L; Lane, David P; Verma, Chandra S","year":2012,"journal":"PloS one, 7(8), e43985","doi":"10.1371/journal.pone.0043985","pmid":"22952838","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01973","title":"Brain responses to high-protein diets.","authors":"Journel, Marion; Chaumontet, Catherine; Darcel, Nicolas; Fromentin, Gilles; Tomé, Daniel","year":2012,"journal":"Advances in nutrition (Bethesda, Md.), 3(3), 322-9","doi":"10.3945/an.112.002071","pmid":"22585905","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"After protein consumption, anorexigenic gut peptide hormones (CCK, GLP-1, peptide YY) are released from the gastrointestinal tract and communicate energy status to the brain via vagal nerve pathways. High-protein diets activate the nucleus tractus solitarius (brainstem) and arcuate nucleus (hypothalamus) more strongly than normal-protein diets.\n\nLeucine specifically triggers two cellular energy sensors — mTOR (mammalian target of rapamycin) and AMPK (AMP-activated protein kinase) — contributing to protein's satiating effect. Additionally, high-protein diets reduce the hedonic response to food through effects on limbic reward circuits, decreasing the motivation to eat beyond metabolic need.","whyItMatters":"Understanding why protein is more satiating than other macronutrients has direct implications for obesity prevention and weight management. The peptide hormones released after protein consumption — particularly GLP-1 and peptide YY — are the same targets as many modern weight loss drugs. This review connects the natural biology of protein-induced satiety with the pharmacological mechanisms being harnessed by anti-obesity medications.","specificNumbers":"","methodology":"This is a narrative review examining published research on the gut-brain signaling pathways activated by protein consumption. The authors synthesized studies on peptide hormone release, vagal nerve signaling, brain activation patterns, and cellular energy sensing mechanisms to provide a comprehensive model of how protein affects appetite and food intake.","limitations":"As a narrative review, this paper synthesizes existing evidence without conducting new experiments or systematic quality assessment. The relative contribution of each gut peptide and brain region to protein-induced satiety is not precisely quantified. Most mechanistic data come from animal studies, and human brain response data are limited. Individual variability in satiety responses to protein is not addressed."},{"rthcId":"RPEP-01974","title":"Effect of intrahippocampal ghrelin agonist administration on passive avoidance learning and anxiety in rats.","authors":"Kajbaf, F; Ahmadi, R; Fatemi Tabatabaie, R; Safarpoor, E","year":2012,"journal":"Pakistan journal of biological sciences : PJBS, 15(22), 1063-8","doi":null,"pmid":"24261121","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01975","title":"Collagen peptides enhance hippocampal neurogenesis and reduce anxiety related behavior in mice.","authors":"Kakoi, Chikako; Udo, Hiroshi; Matsukawa, Taiji; Ohnuki, Koichiro","year":2012,"journal":"Biomedical research (Tokyo, Japan), 33(5), 273-9","doi":null,"pmid":"23124247","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01976","title":"Anorexigenic effects of miglitol in concert with the alterations of gut hormone secretion and gastric emptying in healthy subjects.","authors":"Kaku, H; Tajiri, Y; Yamada, K","year":2012,"journal":"Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme, 44(4), 312-8","doi":"10.1055/s-0032-1304563","pmid":"22351480","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01977","title":"Activation of growth hormone releasing hormone (GHRH) receptor stimulates cardiac reverse remodeling after myocardial infarction (MI).","authors":"Kanashiro-Takeuchi, Rosemeire M; Takeuchi, Lauro M; Rick, Ferenc G; Dulce, Raul; Treuer, Adriana V; Florea, Victoria; Rodrigues, Claudia O; Paulino, Ellena C; Hatzistergos, Konstantinos E; Selem, Sarah M; Gonzalez, Daniel R; Block, Norman L; Schally, Andrew V; Hare, Joshua M","year":2012,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 109(2), 559-63","doi":"10.1073/pnas.1119203109","pmid":"22203988","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01978","title":"The impact of photo-induced molecular changes of dairy proteins on their ACE-inhibitory peptides and activity.","authors":"Kerkaert, Barbara; Mestdagh, Frédéric; Cucu, Tatiana; Shrestha, Kshitij; Van Camp, John; De Meulenaer, Bruno","year":2012,"journal":"Amino acids, 43(2), 951-62","doi":"10.1007/s00726-011-1157-y","pmid":"22116518","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01979","title":"Glucagon-like peptide-1 (GLP-1) receptor agonism or DPP-4 inhibition does not accelerate neoplasia in carcinogen treated mice.","authors":"Kissow, Hannelouise; Hartmann, Bolette; Holst, Jens Juul; Viby, Niels-Erik; Hansen, Lærke Schmidt; Rosenkilde, Mette Marie; Hare, Kristine Juul; Poulsen, Steen Seier","year":2012,"journal":"Regulatory peptides, 179(1-3), 91-100","doi":"10.1016/j.regpep.2012.08.016","pmid":"22989472","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01980","title":"Novel antagonists of growth hormone-releasing hormone inhibit growth and vascularization of human experimental ovarian cancers.","authors":"Klukovits, Anna; Schally, Andrew V; Szalontay, Luca; Vidaurre, Irving; Papadia, Andrea; Zarandi, Marta; Varga, Jozsef L; Block, Norman L; Halmos, Gabor","year":2012,"journal":"Cancer, 118(3), 670-80","doi":"10.1002/cncr.26291","pmid":"21751186","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01981","title":"Evoked axonal oxytocin release in the central amygdala attenuates fear response.","authors":"Knobloch, H Sophie; Charlet, Alexandre; Hoffmann, Lena C; Eliava, Marina; Khrulev, Sergey; Cetin, Ali H; Osten, Pavel; Schwarz, Martin K; Seeburg, Peter H; Stoop, Ron; Grinevich, Valery","year":2012,"journal":"Neuron, 73(3), 553-66","doi":"10.1016/j.neuron.2011.11.030","pmid":"22325206","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01982","title":"Evolution of gnathostome prodynorphin and proenkephalin: characterization of a shark proenkephalin and prodynorphin cDNAs.","authors":"Komorowski, Leanne K; Lecaude, Stephanie G; Westring, Christian G; Danielson, Phillip B; Dores, Robert M","year":2012,"journal":"General and comparative endocrinology, 177(3), 353-64","doi":"10.1016/j.ygcen.2011.12.016","pmid":"22210245","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01983","title":"The association of the appetitive peptide acetylated ghrelin with alcohol craving in early abstinent alcohol dependent individuals.","authors":"Koopmann, Anne; von der Goltz, Christoph; Grosshans, Martin; Dinter, Christina; Vitale, Meike; Wiedemann, Klaus; Kiefer, Falk","year":2012,"journal":"Psychoneuroendocrinology, 37(7), 980-6","doi":"10.1016/j.psyneuen.2011.11.005","pmid":"22172639","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01984","title":"The glucagon receptor is involved in mediating the body weight-lowering effects of oxyntomodulin.","authors":"Kosinski, Jennifer R; Hubert, James; Carrington, Paul E; Chicchi, Gary G; Mu, James; Miller, Corey; Cao, Jin; Bianchi, Elisabetta; Pessi, Antonello; Sinharoy, Ranabir; Marsh, Donald J; Pocai, Alessandro","year":2012,"journal":"Obesity (Silver Spring, Md.), 20(8), 1566-71","doi":"10.1038/oby.2012.67","pmid":"22421924","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01985","title":"Two-layered injectable self-assembling peptide scaffold hydrogels for long-term sustained release of human antibodies.","authors":"Koutsopoulos, Sotirios; Zhang, Shuguang","year":2012,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 160(3), 451-8","doi":"10.1016/j.jconrel.2012.03.014","pmid":"22465676","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01986","title":"The effect of fasting and refeeding on mRNA expression of PepT1 and gastrointestinal hormones regulating digestion and food intake in zebrafish (Danio rerio).","authors":"Koven, William; Schulte, Patricia","year":2012,"journal":"Fish physiology and biochemistry, 38(6), 1565-1575","doi":"10.1007/s10695-012-9649-6","pmid":"22565667","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01987","title":"Cathelicidins: family of antimicrobial peptides. A review.","authors":"Kościuczuk, Ewa M; Lisowski, Paweł; Jarczak, Justyna; Strzałkowska, Nina; Jóźwik, Artur; Horbańczuk, Jarosław; Krzyżewski, Józef; Zwierzchowski, Lech; Bagnicka, Emilia","year":2012,"journal":"Molecular biology reports, 39(12), 10957-70","doi":"10.1007/s11033-012-1997-x","pmid":"23065264","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01988","title":"Rational molecular design of complementary self-assembling peptide hydrogels.","authors":"Kyle, Stuart; Felton, Susan H; McPherson, Michael J; Aggeli, Amalia; Ingham, Eileen","year":2012,"journal":"Advanced healthcare materials, 1(5), 640-5","doi":"10.1002/adhm.201200047","pmid":"23184800","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Complementary charged peptide sequences formed self-supporting hydrogels whose properties could be tuned through charge interactions, with the resulting materials supporting human fibroblast cell viability and proliferation.","whyItMatters":"Rationally designed self-assembling peptide hydrogels could provide tunable biomaterials for tissue engineering, wound healing, and drug delivery, with the charge-based design approach enabling predictable material properties.","specificNumbers":"","methodology":"Complementary charged peptide sequences were rationally designed and synthesized. Hydrogel formation was characterized by biophysical analysis. Biocompatibility was assessed using human fibroblast cell survival and proliferation studies.","limitations":"Brief study with limited detail in the abstract. Only fibroblast cell compatibility was tested. In vivo performance and long-term biocompatibility were not assessed. The abstract provides minimal information about specific peptide sequences or quantitative results."},{"rthcId":"RPEP-01989","title":"Fuel selection and appetite-regulating hormones after intake of a soy protein-based meal replacement.","authors":"König, Daniel; Muser, Klaus; Berg, Aloys; Deibert, Peter","year":2012,"journal":"Nutrition (Burbank, Los Angeles County, Calif.), 28(1), 35-9","doi":"10.1016/j.nut.2011.02.008","pmid":"21778035","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01990","title":"Inhibition of cellular and systemic inflammation cues in human bronchial epithelial cells by melanocortin-related peptides: mechanism of KPV action and a role for MC3R agonists.","authors":"Land, Stephen C","year":2012,"journal":"International journal of physiology, pathophysiology and pharmacology, 4(2), 59-73","doi":null,"pmid":"22837805","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01991","title":"The growth hormone secretagogue receptor (Ghs-R).","authors":"Laviano, Alessandro; Molfino, Alessio; Rianda, Serena; Rossi Fanelli, Filippo","year":2012,"journal":"Current pharmaceutical design, 18(31), 4749-54","doi":null,"pmid":"22632856","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The GHS-R exists in two isoforms: GHS-R1a (active, binds acyl-ghrelin) and GHS-R1b (inactive variant). GHS-R1b modulates the active receptor by forming heterodimeric complexes that reduce GHS-R1a trafficking to the cell surface — an important regulatory mechanism.\n\nGHS-R1a expression extends far beyond the pituitary and hypothalamus to include other brain regions, pancreas, adipose tissue, immune cells, and the cardiovascular system. This distribution underlies ghrelin's pleiotropic effects: growth hormone secretion, appetite stimulation, learning and memory modulation, glucose and lipid metabolism regulation, inflammatory response control, and cardiac performance modulation. The review identifies cancer cachexia, age-related cognitive decline, obesity, and diabetes as conditions that could benefit from GHS-R1a agonists or antagonists.","whyItMatters":"Understanding how a single peptide receptor system can control so many body functions explains why ghrelin-based therapies are being pursued for diverse conditions. The discovery that the inactive GHS-R1b variant regulates the active receptor adds a layer of complexity that could be therapeutically exploited. For conditions like cancer cachexia (where patients waste away), ghrelin receptor agonists could simultaneously stimulate appetite, release growth hormone, and reduce inflammation — addressing multiple aspects of the disease through one target.","specificNumbers":"","methodology":"This is a review article that synthesizes the published literature on the growth hormone secretagogue receptor, covering its molecular biology (isoforms, signal transduction mechanisms), tissue distribution, physiological functions, and therapeutic implications.","limitations":"This is a 2012 review that predates significant advances in GHS-R structural biology and drug development. The therapeutic potential discussed is largely theoretical at the time of writing, with few approved GHS-R-targeted therapies. The complexity of GHS-R signaling (tissue-specific, isoform-dependent) means that drugs targeting this receptor may have unpredictable effects across different organ systems. The review does not include quantitative data or meta-analysis."},{"rthcId":"RPEP-01992","title":"[D-Leu-4]-OB3, a synthetic peptide amide with leptin-like activity, augments the effects of orally delivered exenatide and pramlintide acetate on energy balance and glycemic control in insulin-resistant male C57BLK/6-m db/db mice.","authors":"Leinung, Matthew C; Grasso, Patricia","year":2012,"journal":"Regulatory peptides, 179(1-3), 33-8","doi":"10.1016/j.regpep.2012.08.006","pmid":"22960403","tags":["glp-1-agonists","amylin-analogs","leptin","obesity","diabetes"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Co-administration of [D-Leu-4]-OB3, a synthetic leptin-like peptide, with exenatide resulted in mice that were 4.2% lighter than their starting weight after 14 days — a stark contrast to the 19.7% weight gain in control mice and the 13.9% gain with exenatide alone.\n\nFor blood glucose, co-delivery of [D-Leu-4]-OB3 with exenatide reduced levels by 38.3% (vs. 20.4% for exenatide alone), and co-delivery with pramlintide acetate reduced glucose by 50.5% (vs. 30.2% for pramlintide alone). Notably, the leptin-like peptide also moderated insulin levels, suggesting it may improve insulin sensitivity rather than simply driving more insulin secretion.","whyItMatters":"Most people on GLP-1 drugs like exenatide currently need injections, and adding leptin-pathway activation could amplify weight loss and blood sugar benefits. This study demonstrates that oral delivery of these peptides is feasible and that combining metabolic pathways — incretin, amylin, and leptin — may produce greater effects than any single agent. If these results translate to humans, it could mean more effective oral combination therapies for obesity and type 2 diabetes.","specificNumbers":"4.2% weight loss (combo) vs 19.7% gain (control); blood glucose ↓38.3% (exenatide+OB3) and ↓50.5% (pramlintide+OB3); 14-day treatment","methodology":"Researchers orally delivered exenatide or pramlintide acetate, alone and in combination with [D-Leu-4]-OB3, to insulin-resistant obese db/db mice twice daily for 14 days using absorption enhancers. They measured body weight, food and water intake, blood glucose, and serum insulin levels across treatment groups.","limitations":"This was an animal study using genetically obese mice (db/db), which have a specific leptin receptor mutation that may not reflect typical human obesity. The 14-day treatment period was short, and the study did not assess long-term safety, tolerability, or whether effects persist after stopping treatment. Sample sizes for each group were not clearly specified. The oral absorption enhancer (dodecyl maltoside) used here is not the same technology used in current oral peptide drugs, so the delivery approach may not translate directly."},{"rthcId":"RPEP-01993","title":"The functional coding variant Asn107Ile of the neuropeptide S receptor gene (NPSR1) is associated with schizophrenia and modulates verbal memory and the acoustic startle response.","authors":"Lennertz, Leonhard; Quednow, Boris B; Schuhmacher, Anna; Petrovsky, Nadine; Frommann, Ingo; Schulze-Rauschenbach, Svenja; Landsberg, Martin W; Steinbrecher, Anja; Höfels, Susanne; Pukrop, Ralf; Klosterkötter, Joachim; Franke, Petra E; Wölwer, Wolfgang; Gaebel, Wolfgang; Häfner, Heinz; Maier, Wolfgang; Wagner, Michael; Mössner, Rainald","year":2012,"journal":"The international journal of neuropsychopharmacology, 15(9), 1205-15","doi":"10.1017/S1461145711001623","pmid":"22078257","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The low-functioning NPSR1 Asn107 variant was significantly associated with schizophrenia (OR 1.19, p=0.017) in a case-control sample of 778 schizophrenia patients vs. 713 healthy controls. Patients homozygous for the Asn107 variant showed specifically decreased verbal memory consolidation (while memory acquisition was unaffected). Patients carrying the high-functioning Ile107 variant had significantly reduced startle amplitudes but unaffected prepulse inhibition and habituation.\n\nThese findings translate rodent NPS research into human psychiatric genetics — confirming that NPS receptor function affects both memory and startle response in schizophrenia patients, consistent with animal model predictions.","whyItMatters":"Schizophrenia treatment has been dominated by dopamine-blocking antipsychotics since the 1950s, with limited progress on cognitive symptoms. This study identifies the neuropeptide S system as a potential new drug target for schizophrenia — specifically for the cognitive deficits (like memory problems) that current medications don't address well. The translation from rodent models to human genetic data strengthens the case for NPS-based drug development.","specificNumbers":"n=778 schizophrenia patients + 713 controls · OR 1.19, p=0.017 · Asn107Ile variant (rs324981) · Verbal memory consolidation affected · Startle amplitude reduced in Ile107 carriers","methodology":"Case-control genetic association study. 778 schizophrenia patients and 713 healthy controls were genotyped for the NPSR1 Asn107Ile variant (rs324981). Subsamples of patients underwent cognitive testing (verbal declarative memory) and acoustic startle response measurement, with results stratified by genotype.","limitations":"The odds ratio (1.19) is small, typical of common psychiatric genetic variants but indicating a modest effect size. The study was conducted in a single ethnic population (German), limiting generalizability. Memory and startle testing were done in patient subsamples rather than the full cohort. The association does not prove causation — the variant could be in linkage disequilibrium with the true causal variant."},{"rthcId":"RPEP-01994","title":"Intein-mediated expression, purification, and characterization of thymosin α1-thymopentin fusion peptide in Escherichia coli.","authors":"Li, Juan; Zheng, Lei; Li, Pingli; Wang, Fengshan","year":2012,"journal":"Protein expression and purification, 84(1), 1-8","doi":"10.1016/j.pep.2012.04.013","pmid":"22554820","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01995","title":"Treatment of obesity by endoscopic gastric intramural injection of botulinum toxin A: a randomized clinical trial.","authors":"Li, Li; Liu, Qing-Sen; Liu, Wen-Hui; Yang, Yun-Sheng; Yan, Dou; Peng, Li-Hua; Li, Lian-Yong; Meng, Jiang-Yun; Wang, Xiang-Dong; Ke, Meng","year":2012,"journal":"Hepato-gastroenterology, 59(118), 2003-7","doi":"10.5754/hge11755","pmid":"22193433","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Both treatment groups (200U and 300U BTX-A) showed significant decreases in body weight and BMI (p<0.05). Gastric emptying times increased, particularly at 1 week post-treatment. Fasting ghrelin levels decreased significantly at 4 weeks after treatment. PYY levels decreased, especially at 12 weeks. Triglyceride levels also fell. No severe complications were observed across all 19 patients who completed follow-up.","whyItMatters":"Obesity treatment options between lifestyle changes and bariatric surgery have historically been limited. This study explored an intermediate approach — using an endoscopic procedure with botulinum toxin (a peptide-based neurotoxin) to modify stomach function without surgery. The discovery that it also reduces ghrelin levels suggests the mechanism goes beyond simply slowing digestion to actually modulating appetite-regulating peptide hormones.","specificNumbers":"","methodology":"Randomized clinical trial of 20 obese patients (BMI >28 kg/m²) divided into two groups: 200U and 300U of botulinum toxin A. The toxin was injected endoscopically at 20 sites in the gastric wall including the fundus. Body weight, BMI, gastric emptying times, and blood levels of cholesterol, triglycerides, insulin, leptin, motilin, PYY, and ghrelin were measured before treatment and at 1, 4, and 12 weeks after treatment.","limitations":"Very small sample size (20 patients, 19 completers) severely limits statistical power and generalizability. There was no placebo/sham endoscopy control group, making it impossible to separate treatment effects from placebo effects. The 12-week follow-up is too short to assess durability of weight loss. The two dose groups were not compared to each other in a meaningful way. No blinding is mentioned. The decrease in PYY (a satiety hormone) after treatment is paradoxical and unexplained."},{"rthcId":"RPEP-01996","title":"Opioid glycopeptide analgesics derived from endogenous enkephalins and endorphins.","authors":"Li, Yingxue; Lefever, Mark R; Muthu, Dhanasekaran; Bidlack, Jean M; Bilsky, Edward J; Polt, Robin","year":2012,"journal":"Future medicinal chemistry, 4(2), 205-26","doi":"10.4155/fmc.11.195","pmid":"22300099","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01997","title":"Dragon's blood inhibits chronic inflammatory and neuropathic pain responses by blocking the synthesis and release of substance P in rats.","authors":"Li, Yu-Sang; Wang, Jun-Xian; Jia, Mei-Mei; Liu, Min; Li, Xiao-Jun; Tang, He-Bin","year":2012,"journal":"Journal of pharmacological sciences, 118(1), 43-54","doi":null,"pmid":"22198006","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01998","title":"Cultivation of human neural progenitor cells in a 3-dimensional self-assembling peptide hydrogel.","authors":"Liedmann, Andrea; Rolfs, Arndt; Frech, Moritz J","year":2012,"journal":"Journal of visualized experiments : JoVE, e3830","doi":"10.3791/3830","pmid":"22258286","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-01999","title":"Absence of C-C motif chemokine ligand 5 in mice leads to decreased local macrophage recruitment and behavioral hypersensitivity in a murine neuropathic pain model.","authors":"Liou, Jiin-Tarng; Yuan, Hui-Bih; Mao, Chih-Chieh; Lai, Ying-Shu; Day, Yuan-Ji","year":2012,"journal":"Pain, 153(6), 1283-1291","doi":"10.1016/j.pain.2012.03.008","pmid":"22494919","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02000","title":"Pigment epithelium-derived factor (PEDF) peptide eye drops reduce inflammation, cell death and vascular leakage in diabetic retinopathy in Ins2(Akita) mice.","authors":"Liu, Yanling; Leo, Lan Franco; McGregor, Corban; Grivitishvili, Anzor; Barnstable, Colin J; Tombran-Tink, Joyce","year":2012,"journal":"Molecular medicine (Cambridge, Mass.), 18(1), 1387-401","doi":"10.2119/molmed.2012.00008","pmid":"23019073","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Two PEDF-derived peptide eye drops (P60, antiangiogenic; P78, neuroprotective) penetrated through the cornea and reached the retina within 1-4 hours when applied topically to diabetic mice. Both peptides reduced vascular leakage by ~60% and restored tight junction proteins (ZO1 and occludin) to non-diabetic levels. The neuroprotective P78 peptide reduced inflammatory cytokines (9 of 20 measured, including TNF-α, IL-6, and IFN-γ), prevented microglia activation by ~60%, reduced retinal ganglion cell death by ~22%, and prevented inner retinal thinning by ~13%. These effects were achieved with just once-weekly eye drops for 15 weeks.","whyItMatters":"Diabetic retinopathy is the leading cause of blindness in working-age adults, and current treatments (laser therapy, injections into the eye) are invasive and burdensome. This study shows that peptide eye drops — applied just once a week — can penetrate to the retina and simultaneously address three major aspects of diabetic eye disease: vascular leakage, inflammation, and nerve cell death. If this works in humans, it could replace painful eye injections with simple drops.","specificNumbers":"","methodology":"Ins2(Akita) mice (a genetic model of type 1 diabetes) received PEDF peptide eye drops once weekly for 15 weeks starting at the onset of high blood sugar. Peptides were fluorescently labeled to track their penetration through the eye. Researchers measured vascular leakage, tight junction protein expression, inflammatory cytokine levels (20 cytokines), microglia activation, retinal ganglion cell survival, and retinal layer thickness. Signaling pathways (ERK1/2, AKT) were analyzed in Müller glial cells.","limitations":"This was an animal study in a genetic mouse model of diabetes, which may not perfectly replicate human diabetic retinopathy. The once-weekly dosing achieved moderate vitreous concentrations, and optimal dosing for humans is unknown. Only type 1 diabetic mice were studied. Long-term safety of repeated topical peptide application wasn't assessed beyond 15 weeks."},{"rthcId":"RPEP-02001","title":"Injectable shear-thinning hydrogels engineered with a self-assembling Dock-and-Lock mechanism.","authors":"Lu, Hoang D; Charati, Manoj B; Kim, Iris L; Burdick, Jason A","year":2012,"journal":"Biomaterials, 33(7), 2145-53","doi":"10.1016/j.biomaterials.2011.11.076","pmid":"22177842","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02002","title":"In vitro selection of unnatural cyclic peptide libraries via mRNA display.","authors":"Ma, Zhong; Hartman, Matthew C T","year":2012,"journal":"Methods in molecular biology (Clifton, N.J.), 805, 367-90","doi":"10.1007/978-1-61779-379-0_21","pmid":"22094817","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02003","title":"Orexin modulates brown adipose tissue thermogenesis.","authors":"Madden, Christopher J; Tupone, Domenico; Morrison, Shaun F","year":2012,"journal":"Biomolecular concepts, 3(4), 381-386","doi":null,"pmid":"23293681","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02004","title":"Involvement of tachykinins and NK1 receptor in the joint inflammation with collagen type II-specific monoclonal antibody-induced arthritis in mice.","authors":"Makino, Akira; Sakai, Atsushi; Ito, Hiromoto; Suzuki, Hidenori","year":2012,"journal":"Journal of Nippon Medical School = Nippon Ika Daigaku zasshi, 79(2), 129-38","doi":null,"pmid":"22687356","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02005","title":"Synthesis of ghrelin: chemical synthesis and semisynthesis for large-scale preparation of modified peptides.","authors":"Makino, Tomohiro; Matsumoto, Masaru; Minamitake, Yoshiharu","year":2012,"journal":"Methods in enzymology, 514, 183-203","doi":"10.1016/B978-0-12-381272-8.00012-X","pmid":"22975054","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02006","title":"Oxytocin and vasopressin agonists and antagonists as research tools and potential therapeutics.","authors":"Manning, M; Misicka, A; Olma, A; Bankowski, K; Stoev, S; Chini, B; Durroux, T; Mouillac, B; Corbani, M; Guillon, G","year":2012,"journal":"Journal of neuroendocrinology, 24(4), 609-28","doi":"10.1111/j.1365-2826.2012.02303.x","pmid":"22375852","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02007","title":"Solid-phase-assisted synthesis of targeting peptide-PEG-oligo(ethane amino)amides for receptor-mediated gene delivery.","authors":"Martin, Irene; Dohmen, Christian; Mas-Moruno, Carlos; Troiber, Christina; Kos, Petra; Schaffert, David; Lächelt, Ulrich; Teixidó, Meritxell; Günther, Michael; Kessler, Horst; Giralt, Ernest; Wagner, Ernst","year":2012,"journal":"Organic & biomolecular chemistry, 10(16), 3258-68","doi":"10.1039/c2ob06907e","pmid":"22407126","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02008","title":"Recombinant protein purification using complementary peptides as affinity tags.","authors":"Martínez-Ceron, María C; Targovnik, Alexandra M; Urtasun, Nicolás; Cascone, Osvaldo; Miranda, María V; Camperi, Silvia A","year":2012,"journal":"New biotechnology, 29(2), 206-10","doi":"10.1016/j.nbt.2011.05.008","pmid":"21664994","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02009","title":"The pharmacology of neurotrophic treatment with Cerebrolysin: brain protection and repair to counteract pathologies of acute and chronic neurological disorders.","authors":"Masliah, E; Díez-Tejedor, E","year":2012,"journal":"Drugs of today (Barcelona, Spain : 1998), 48 Suppl A, 3-24","doi":"10.1358/dot.2012.48(Suppl.A).1739716","pmid":"22514792","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02010","title":"Breaking the loop: oxytocin as a potential treatment for drug addiction.","authors":"McGregor, Iain S; Bowen, Michael T","year":2012,"journal":"Hormones and behavior, 61(3), 331-9","doi":"10.1016/j.yhbeh.2011.12.001","pmid":"22198308","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02011","title":"Ghrelin treatment of cachectic patients with chronic obstructive pulmonary disease: a multicenter, randomized, double-blind, placebo-controlled trial.","authors":"Miki, Keisuke; Maekura, Ryoji; Nagaya, Noritoshi; Nakazato, Masamitsu; Kimura, Hiroshi; Murakami, Shinsuke; Ohnishi, Shunsuke; Hiraga, Toru; Miki, Mari; Kitada, Seigo; Yoshimura, Kenji; Tateishi, Yoshitaka; Arimura, Yasuji; Matsumoto, Nobuhiro; Yoshikawa, Masanori; Yamahara, Kenichi; Kangawa, Kenji","year":2012,"journal":"PloS one, 7(5), e35708","doi":"10.1371/journal.pone.0035708","pmid":"22563468","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02012","title":"Endothelin B receptors contribute to retinal ganglion cell loss in a rat model of glaucoma.","authors":"Minton, Alena Z; Phatak, Nitasha R; Stankowska, Dorota L; He, Shaoqing; Ma, Hai-Ying; Mueller, Brett H; Jiang, Ming; Luedtke, Robert; Yang, Shaohua; Brownlee, Colby; Krishnamoorthy, Raghu R","year":2012,"journal":"PloS one, 7(8), e43199","doi":"10.1371/journal.pone.0043199","pmid":"22916224","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02013","title":"A nociceptive signaling role for neuromedin B.","authors":"Mishra, Santosh K; Holzman, Sarah; Hoon, Mark A","year":2012,"journal":"The Journal of neuroscience : the official journal of the Society for Neuroscience, 32(25), 8686-95","doi":"10.1523/JNEUROSCI.1533-12.2012","pmid":"22723708","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Neuromedin B (NMB) was identified in trigeminal ganglion sensory neurons that co-express CGRP and TRPV1, placing it in nociceptive (pain-sensing) circuits. Blocking NMB with an antagonist greatly attenuated edema and nerve sensitization caused by mustard oil stimulation, while direct NMB injection caused local swelling and pain sensitization.\n\nThe NMB receptor was found on interneurons in the superficial dorsal horn of the spinal cord. When these NMBR-expressing neurons were selectively destroyed using NMB-saporin, mice showed impaired responses to noxious heat but maintained normal responses to mechanical stimuli and itch, demonstrating NMB's selective role in thermal nociception.","whyItMatters":"This study identifies a neuropeptide pathway selectively involved in heat pain perception, which is distinct from mechanical pain and itch pathways. Understanding how specific neuropeptides control different types of pain could lead to more targeted pain treatments that block specific pain modalities without affecting other sensory functions.","specificNumbers":"","methodology":"Researchers used array-based differential screening to identify NMB expression in mouse trigeminal ganglia. Double-labeling immunohistochemistry confirmed co-expression with CGRP and TRPV1. Functional experiments included NMB antagonist administration during mustard oil-induced neurogenic inflammation, direct NMB injection to test nociceptive effects, and NMB-saporin ablation of NMBR-expressing spinal cord neurons to assess modality-specific pain responses.","limitations":"The study was conducted entirely in mice, so the role of NMB in human pain perception remains to be confirmed. The NMB-saporin ablation technique permanently destroys neurons, which may not perfectly mimic pharmacological NMB blockade. The study focused on acute pain models and did not assess NMB's role in chronic pain conditions."},{"rthcId":"RPEP-02014","title":"Comparative study of therapeutic effects of short- and long-acting loop diuretics in outpatients with chronic heart failure (COLD-CHF).","authors":"Miyata, Masaaki; Sasaki, Takeshi; Ikeda, Yoshiyuki; Shinsato, Takuro; Kubozono, Takuro; Furusho, Yuko; Kusumoto, Atsushi; Hamasaki, Shuichi; Tei, Chuwa","year":2012,"journal":"Journal of cardiology, 59(3), 352-8","doi":"10.1016/j.jjcc.2011.12.007","pmid":"22365947","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02015","title":"Ghrelin level and body weight loss after esophagectomy for esophageal cancer.","authors":"Miyazaki, Tatsuya; Tanaka, Naritaka; Hirai, Hanako; Yokobori, Takehiko; Sano, Akihiko; Sakai, Makoto; Inose, Takanori; Sohda, Makoto; Nakajima, Masanobu; Fukuchi, Minoru; Kato, Hiroyuki; Kuwano, Hiroyuki","year":2012,"journal":"The Journal of surgical research, 176(1), 74-8","doi":"10.1016/j.jss.2011.09.016","pmid":"22137988","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02016","title":"The oxytocin system in drug discovery for autism: animal models and novel therapeutic strategies.","authors":"Modi, Meera E; Young, Larry J","year":2012,"journal":"Hormones and behavior, 61(3), 340-50","doi":"10.1016/j.yhbeh.2011.12.010","pmid":"22206823","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02017","title":"The role of lactoferrin binding protein B in mediating protection against human lactoferricin.","authors":"Morgenthau, Ari; Livingstone, Margaret; Adamiak, Paul; Schryvers, Anthony B","year":2012,"journal":"Biochemistry and cell biology = Biochimie et biologie cellulaire, 90(3), 417-23","doi":"10.1139/o11-074","pmid":"22332888","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Lactoferrin binding protein B (LbpB) from two different Gram-negative bacterial species (Moraxella and Neisseria) provided protection against killing by human lactoferricin. The proposed mechanism involves clusters of negatively charged amino acids in the C-terminal lobe of LbpB that electrostatically interact with the positively charged (cationic) lactoferricin peptide, effectively sequestering it before it can insert into and disrupt the bacterial membrane.\n\nThe study also investigated the prevalence and sequence diversity of lactoferrin receptors across bacterial species, suggesting that LbpB-mediated defense against antimicrobial peptides is a widespread strategy among mucosal pathogens.","whyItMatters":"Understanding how bacteria resist antimicrobial peptides is critical for developing peptide-based antibiotics. Lactoferricin is one of the most studied antimicrobial peptides, and the discovery that bacteria can neutralize it through a specific receptor protein reveals a vulnerability in peptide-based immune defense. This knowledge could guide the design of modified antimicrobial peptides that evade LbpB-mediated resistance, or the development of combination therapies that block LbpB to restore lactoferricin's effectiveness.","specificNumbers":"","methodology":"Researchers tested LbpB from two bacterial species for its ability to protect against human lactoferricin killing activity using antimicrobial sensitivity assays. They analyzed the amino acid sequences of LbpB proteins across multiple bacterial species to identify conserved features, particularly the negatively charged amino acid clusters in the C-terminal region proposed to mediate peptide neutralization.","limitations":"The study tested LbpB from only two bacterial species, and the protective mechanism (electrostatic charge neutralization) is proposed based on sequence analysis rather than direct structural evidence. The in vivo relevance of LbpB-mediated protection — whether it meaningfully affects infection outcomes in humans — was not assessed. The study focused on lactoferricin specifically and did not test whether LbpB protects against other cationic antimicrobial peptides."},{"rthcId":"RPEP-02018","title":"The mechanical stimulation of cells in 3D culture within a self-assembling peptide hydrogel.","authors":"Nagai, Yusuke; Yokoi, Hidenori; Kaihara, Keiko; Naruse, Keiji","year":2012,"journal":"Biomaterials, 33(4), 1044-51","doi":"10.1016/j.biomaterials.2011.10.049","pmid":"22056753","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02019","title":"Interaction of the synthetic peptide octarphin with rat adrenal cortex membranes.","authors":"Nekrasova, Y N; Zolotarev, Y A; Navolotskaya, E V","year":2012,"journal":"Biochemistry. Biokhimiia, 77(12), 1377-81","doi":"10.1134/S000629791212005X","pmid":"23244733","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02020","title":"Detection of nonopioid β-endorphin receptor in the rat myocardium.","authors":"Nekrasova, Yulia N; Zolotarev, Yury A; Navolotskaya, Elena V","year":2012,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 18(2), 83-7","doi":"10.1002/psc.1417","pmid":"22052815","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02021","title":"Synthetic peptide TPLVTLFK (octarphin) reduces the corticosterone production by rat adrenal cortex through nonopioid β-endorphin receptor.","authors":"Nekrasova, Yuliia N; Zolotarev, Yury A; Navolotskaya, Elena V","year":2012,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 18(8), 495-9","doi":"10.1002/psc.2424","pmid":"22744732","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02022","title":"Melanotan II injection resulting in systemic toxicity and rhabdomyolysis.","authors":"Nelson, Michael E; Bryant, Sean M; Aks, Steven E","year":2012,"journal":"Clinical toxicology (Philadelphia, Pa.), 50(10), 1169-73","doi":"10.3109/15563650.2012.740637","pmid":"23121206","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02023","title":"Balance of brain oxytocin and vasopressin: implications for anxiety, depression, and social behaviors.","authors":"Neumann, Inga D; Landgraf, Rainer","year":2012,"journal":"Trends in neurosciences, 35(11), 649-59","doi":"10.1016/j.tins.2012.08.004","pmid":"22974560","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02024","title":"The role of copeptin as a diagnostic and prognostic biomarker for risk stratification in the emergency department.","authors":"Nickel, Christian H; Bingisser, Roland; Morgenthaler, Nils G","year":2012,"journal":"BMC medicine, 10, 7","doi":"10.1186/1741-7015-10-7","pmid":"22264220","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Copeptin, the C-terminal fragment of the arginine vasopressin precursor, serves as a stable and sensitive surrogate marker for vasopressin release. The review found that copeptin measurement is useful as a prognostic marker across multiple acute conditions seen in emergency departments, including lower respiratory tract infections, heart disease, and stroke.\n\nThe key advantage of copeptin over vasopressin itself is stability — vasopressin degrades rapidly in blood samples, making it difficult to measure accurately, while copeptin remains stable and can be reliably quantified with standard laboratory assays.","whyItMatters":"Emergency departments need fast, reliable tools to identify which patients are most at risk. Copeptin offers a single blood test that reflects the body's stress response and can help predict who will deteriorate. Since it's derived from the vasopressin pathway — a peptide system central to the body's response to acute illness — it captures something traditional tests might miss.","specificNumbers":"","methodology":"This was a narrative review summarizing recent published research on copeptin as a diagnostic and prognostic biomarker. The authors evaluated studies examining copeptin's clinical utility in emergency department settings, focusing on its role in risk stratification for patients presenting with acute conditions.","limitations":"As a narrative review rather than a systematic review or meta-analysis, this paper may not capture all available evidence and could be subject to selection bias. The review was published in 2012, so newer studies on copeptin utility may have emerged since. Specific cutoff values and cost-effectiveness were not fully established at the time of publication."},{"rthcId":"RPEP-02025","title":"Factors that restrict the cell permeation of cyclic prodrugs of an opioid peptide, part 3: Synthesis of analogs designed to have improved stability to oxidative metabolism.","authors":"Nofsinger, Rebecca; Fuchs-Knotts, Tarra; Borchardt, Ronald T","year":2012,"journal":"Journal of pharmaceutical sciences, 101(9), 3486-99","doi":"10.1002/jps.23109","pmid":"22411763","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02026","title":"Factors that restrict the cell permeation of cyclic prodrugs of an opioid peptide, part 4: Characterization of the biopharmaceutical and physicochemical properties of two new cyclic prodrugs designed to be stable to oxidative metabolism by cytochrome P-450 enzymes in the intestinal mucosa.","authors":"Nofsinger, Rebecca; Borchardt, Ronald T","year":2012,"journal":"Journal of pharmaceutical sciences, 101(9), 3500-10","doi":"10.1002/jps.23079","pmid":"22337204","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Two new cyclic prodrugs of enkephalin opioid peptides (CA-[Cha(4), D-Leu(5)]-Enk and CA-[Cha(4), D-Ala(5)]-Enk) were designed and characterized:\n\n- Structural success: NMR and molecular dynamics showed type I β-turn conformations favorable for transcellular permeation\n- Physicochemical success: Higher lipophilicity than linear peptides (better for cell crossing)\n- Metabolic success: Stable to cytochrome P-450 oxidative metabolism in intestinal mucosa\n- Absorption failure: Caco-2 cell studies revealed the prodrugs are substrates for P-glycoprotein and other apically polarized efflux transporters\n- In vivo confirmation: Rat intestinal perfusion confirmed poor intestinal permeation\n\nConclusion: Oral absorption of cyclic peptide prodrugs requires designing molecules that avoid both CYP enzyme metabolism AND efflux transporter recognition.","whyItMatters":"Most peptide drugs must be injected because they can't survive oral delivery. This is a major barrier to patient compliance — imagine if insulin or GLP-1 drugs could simply be swallowed. This study identifies a critical lesson: even when you solve the enzyme degradation problem, efflux transporters can independently block absorption. Understanding that oral peptide delivery requires overcoming both barriers simultaneously is essential for designing the next generation of oral peptide drugs.","specificNumbers":"","methodology":"The two cyclic prodrugs were characterized using two-dimensional NMR spectroscopy for solution conformation and molecular dynamics simulations for structural analysis. Physicochemical properties (molecular surface area, cLog P) were calculated. Caco-2 cell monolayer permeation studies assessed transcellular transport and identified efflux transporter substrate activity. An in situ rat intestinal perfusion model validated intestinal permeation and metabolic stability in vivo.","limitations":"Only two specific cyclic prodrugs were tested, so the findings may not generalize to all cyclic peptides. Caco-2 cells are an imperfect model of human intestinal epithelium. The rat perfusion model may not perfectly predict human oral absorption. The study focuses on the barriers to absorption but doesn't propose solutions for the efflux transporter problem. The opioid peptide backbone used may have unique transporter recognition features not shared by other therapeutic peptides."},{"rthcId":"RPEP-02027","title":"Neural responsivity to food cues in fasted and fed states pre and post gastric bypass surgery.","authors":"Ochner, Christopher N; Laferrère, Blandine; Afifi, Ladan; Atalayer, Deniz; Geliebter, Allan; Teixeira, Julio","year":2012,"journal":"Neuroscience research, 74(2), 138-43","doi":"10.1016/j.neures.2012.08.002","pmid":"22921709","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02028","title":"Melanotan-associated melanoma in situ.","authors":"Ong, Suyin; Bowling, Jonathan","year":2012,"journal":"The Australasian journal of dermatology, 53(4), 301-2","doi":"10.1111/j.1440-0960.2012.00915.x","pmid":"22724573","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02029","title":"Structure and mechanism for recognition of peptide hormones by Class B G-protein-coupled receptors.","authors":"Pal, Kuntal; Melcher, Karsten; Xu, H Eric","year":2012,"journal":"Acta pharmacologica Sinica, 33(3), 300-11","doi":"10.1038/aps.2011.170","pmid":"22266723","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Class B GPCRs share a common structural blueprint for peptide hormone recognition. The extracellular domain (ECD) provides high-affinity, specific binding through a conserved fold, while the seven-transmembrane domain handles receptor activation and G-protein coupling. Structural studies of multiple Class B GPCR ECDs revealed general principles governing how these receptors distinguish between different peptide hormones.\n\nThese structural insights have direct implications for designing peptide hormone analogs — understanding which parts of the peptide interact with the ECD versus the transmembrane domain helps researchers engineer modified peptides with improved selectivity, potency, or duration of action.","whyItMatters":"Class B GPCRs are the targets for some of the most commercially important peptide drugs in medicine — including GLP-1 agonists for diabetes and weight loss (semaglutide, tirzepatide), parathyroid hormone analogs for osteoporosis (teriparatide), and calcitonin for bone diseases. Understanding exactly how these receptors bind peptide hormones is the foundation for designing next-generation drugs with better potency, selectivity, and fewer side effects.","specificNumbers":"","methodology":"This is a structural biology review that synthesizes published crystal structures, NMR data, and biochemical studies of Class B GPCR extracellular domains. It compares receptor structures across multiple family members to identify common principles of peptide hormone recognition.","limitations":"At the time of publication (2012), full-length Class B GPCR structures had not yet been solved — only the extracellular domains were structurally characterized. This limited understanding of how ECD binding triggers transmembrane domain activation. The review necessarily reflects the structural knowledge available at the time, and significant advances in cryo-EM have since revealed much more."},{"rthcId":"RPEP-02030","title":"Differences in basal and ethanol-induced levels of opioid peptides in Wistar rats from five different suppliers.","authors":"Palm, Sara; Roman, Erika; Nylander, Ingrid","year":2012,"journal":"Peptides, 36(1), 1-8","doi":"10.1016/j.peptides.2012.04.016","pmid":"22564490","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02031","title":"Identification of ghrelin receptor blocker, D-[Lys3] GHRP-6 as a CXCR4 receptor antagonist.","authors":"Patel, Kalpesh; Dixit, Vishwa Deep; Lee, Jun Ho; Kim, Jie Wan; Schaffer, Eric M; Nguyen, Dzung; Taub, Dennis D","year":2012,"journal":"International journal of biological sciences, 8(1), 108-17","doi":null,"pmid":"22211109","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"D-[Lys3] GHRP-6 (DLS), widely used as a 'selective' ghrelin receptor antagonist, was unexpectedly found to also block the CXCR4 chemokine receptor. DLS blocked CXCL12 binding and signaling through CXCR4 on T cells and PBMCs. Because CXCR4 is a major co-receptor for HIV-1 entry into CD4+ cells, DLS partially blocked HIV-1 entry and replication in activated human PBMCs.\n\nThis means that many published studies using DLS as a 'specific' ghrelin receptor tool may have confounded results, as DLS has dual receptor activity. It also suggests that structural analogs of DLS could potentially block HIV infection, CXCR4-dependent cancer cell migration, and inflammatory immune cell trafficking.","whyItMatters":"This finding has two major implications. First, it calls into question the results of numerous studies that used DLS as a 'selective' ghrelin receptor blocker — any effects attributed to ghrelin receptor blockade could have been partly or wholly due to CXCR4 inhibition. Second, it opens an unexpected therapeutic avenue: a ghrelin-related peptide that can block HIV entry into immune cells, potentially leading to novel anti-HIV or anti-cancer peptide therapeutics based on DLS structural analogs.","specificNumbers":"DLS blocks both GHS-R1a and CXCR4 · CXCL12 binding inhibited · HIV-1 entry partially blocked · T cell and PBMC effects confirmed · Dual receptor activity demonstrated","methodology":"Researchers tested DLS for CXCR4 activity using CXCL12 binding and chemotaxis assays on T cells and PBMCs. Calcium signaling was measured to confirm functional CXCR4 blockade. HIV-1 entry and propagation were assessed in activated human PBMCs in the presence and absence of DLS.","limitations":"DLS only partially (not completely) blocked HIV-1 entry, suggesting it is a moderate CXCR4 antagonist. The study does not determine whether DLS acts as a competitive or allosteric CXCR4 antagonist. The binding affinity for CXCR4 versus GHS-R1a was not directly compared. In vivo validation of the anti-HIV or anti-CXCR4 effects was not performed. The HIV blocking was demonstrated in cell culture, not in animal models or patients."},{"rthcId":"RPEP-02032","title":"Expedient chemical synthesis of 75mer DNA binding domain of MafA: an insight on its binding to insulin enhancer.","authors":"Pellegrino, Sara; Annoni, Chiara; Contini, Alessandro; Clerici, Francesca; Gelmi, Maria Luisa","year":2012,"journal":"Amino acids, 43(5), 1995-2003","doi":"10.1007/s00726-012-1274-2","pmid":"22476346","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02033","title":"Ghrelin inhibits insulin release by regulating the expression of inwardly rectifying potassium channel 6.2 in islets.","authors":"Peng, Zhang; Xiaolei, Zhou; Al-Sanaban, Hani; Chengrui, Xue; Shengyi, You","year":2012,"journal":"The American journal of the medical sciences, 343(3), 215-9","doi":"10.1097/MAJ.0b013e31824390b9","pmid":"22270395","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02034","title":"Cardioprotection against ischemia/reperfusion injury and chromogranin A-derived peptides.","authors":"Penna, C; Tullio, F; Perrelli, M-G; Mancardi, D; Pagliaro, P","year":2012,"journal":"Current medicinal chemistry, 19(24), 4074-85","doi":null,"pmid":"22834798","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02035","title":"Antagonists of growth hormone-releasing hormone suppress in vivo tumor growth and gene expression in triple negative breast cancers.","authors":"Perez, Roberto; Schally, Andrew V; Vidaurre, Irving; Rincon, Ricardo; Block, Norman L; Rick, Ferenc G","year":2012,"journal":"Oncotarget, 3(9), 988-97","doi":null,"pmid":"22941871","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Treatment with the GHRH antagonist peptide MIA-602 significantly reduced tumor growth in mice bearing xenografts of two human TNBC cell lines (HCC1806 and MX-1).\n\nGene expression analysis revealed significant suppression of multiple inflammatory cytokines: IFNγ, IL-1α, IL-4, IL-6, IL-8, IL-10, and TNFα. These inflammatory cytokines are known to promote epithelial-mesenchymal transitions (EMT), drug resistance, and metastatic potential in breast cancer. siRNA silencing of GHRH receptors in vitro confirmed that the effects were receptor-mediated, inhibiting both GHRH-R genes and inflammatory cytokine expression.","whyItMatters":"Triple negative breast cancer is the most aggressive subtype and has the fewest treatment options — it doesn't respond to estrogen, progesterone, or HER2-targeted therapies. Finding that a peptide-based GHRH antagonist can both shrink these tumors and suppress the inflammatory signals that drive their resistance and spread opens a potential new treatment avenue for these patients.","specificNumbers":"","methodology":"In vivo studies used nude mice bearing xenografts of human TNBC cell lines HCC1806 and MX-1, treated with MIA-602. Tumor growth was measured. Quantitative gene expression analysis assessed inflammatory cytokine transcripts (IFNγ, IL-1α, IL-4, IL-6, IL-8, IL-10, TNFα). In vitro studies used siRNA-mediated GHRH receptor silencing to confirm receptor-dependent mechanisms in both cell lines.","limitations":"This is a preclinical study using human tumor xenografts in immunocompromised nude mice, which does not fully replicate the human immune environment. The anti-tumor effects of MIA-602 in the context of a functional immune system are unknown. Clinical translation would require demonstration of efficacy and safety in human trials. The study focused on gene expression rather than protein-level cytokine measurements for most targets."},{"rthcId":"RPEP-02036","title":"Growth hormone response to growth hormone-releasing peptide-2 in growth hormone-deficient little mice.","authors":"Peroni, Cibele N; Hayashida, Cesar Y; Nascimento, Nancy; Longuini, Viviane C; Toledo, Rodrigo A; Bartolini, Paolo; Bowers, Cyril Y; Toledo, Sergio P A","year":2012,"journal":"Clinics (Sao Paulo, Brazil), 67(3), 265-72","doi":null,"pmid":"22473409","tags":[],"studyType":"animal-study","evidenceStrength":"low-moderate","keyFinding":"GHRP-2 (growth hormone-releasing peptide-2) stimulated significant growth hormone release in 'little' (lit/lit) mice that have mutated, non-functional GHRH receptors — proving that GHRP-2 can trigger growth hormone release independently of the GHRH signaling pathway. Lit/lit mice injected with 10 mcg GHRP-2 released 9.3±1.5 ng/ml GH vs 1.04±1.15 ng/ml in controls (p<0.001).\n\nHeterozygous lit/+ mice showed intermediate GH release (34.5±9.7 ng/ml), while wild-type mice had the highest response (163±46 ng/ml). This dose-response pattern across genotypes demonstrates that GHRP-2's effect is partially but not fully dependent on GHRH signaling — it works through a separate pathway via the ghrelin receptor (GHS-R1a) on remaining pituitary somatotroph cells.","whyItMatters":"This study proves that growth hormone-releasing peptides like GHRP-2 have their own independent pathway for stimulating growth hormone, separate from the traditional GHRH system. This means GHRP-2 could potentially help patients whose growth hormone deficiency is caused by GHRH receptor problems — a subset of GH-deficient individuals who wouldn't respond to GHRH-based therapies.","specificNumbers":"GHRP-2 dose: 10 mcg · lit/lit GH response: 9.3±1.5 ng/ml vs 1.04±1.15 controls · lit/+ response: 34.5±9.7 ng/ml · Wild-type: 163±46 ng/ml · p<0.001","methodology":"Researchers compared acute growth hormone response to injected GHRP-2 in three groups of mice: lit/lit mice (homozygous for GHRH receptor mutation, severe GH deficiency), lit/+ heterozygous littermates (intermediate GH function), and wild-type C57BL/6J mice. Serum growth hormone was measured after 10 mcg GHRP-2 injection. Plasma leptin and ghrelin levels were also evaluated at baseline and after stimulation.","limitations":"Mouse model — the magnitude of GHRP-2's GHRH-independent effect may differ in humans. The lit/lit mouse model is a specific genetic form of GH deficiency that doesn't represent all causes. The study used a single acute dose, not chronic treatment. The GH response in lit/lit mice, while statistically significant, was very small compared to wild-type (9.3 vs 163 ng/ml), raising questions about clinical meaningfulness."},{"rthcId":"RPEP-02037","title":"The human tripeptide GHK-Cu in prevention of oxidative stress and degenerative conditions of aging: implications for cognitive health.","authors":"Pickart, Loren; Vasquez-Soltero, Jessica Michelle; Margolina, Anna","year":2012,"journal":"Oxidative medicine and cellular longevity, 2012, 324832","doi":"10.1155/2012/324832","pmid":"22666519","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02038","title":"Activation of neurokinin-1 receptor by substance P inhibits melanogenesis in B16-F10 melanoma cells.","authors":"Ping, Fengfeng; Shang, Jing; Zhou, Jia; Song, Jing; Zhang, Luyong","year":2012,"journal":"The international journal of biochemistry & cell biology, 44(12), 2342-8","doi":"10.1016/j.biocel.2012.09.025","pmid":"23041339","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02039","title":"Growth hormone secretagogues: out of competition.","authors":"Pinyot, Armand; Nikolovski, Zoran; Bosch, Jaume; Such-Sanmartín, Gerard; Kageyama, Shinji; Segura, Jordi; Gutiérrez-Gallego, Ricardo","year":2012,"journal":"Analytical and bioanalytical chemistry, 402(3), 1101-8","doi":"10.1007/s00216-011-5544-8","pmid":"22083629","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02040","title":"Stapling mimics noncovalent interactions of γ-carboxyglutamates in conantokins, peptidic antagonists of N-methyl-D-aspartic acid receptors.","authors":"Platt, Randall J; Han, Tiffany S; Green, Brad R; Smith, Misty D; Skalicky, Jack; Gruszczynski, Pawel; White, H Steve; Olivera, Baldomero; Bulaj, Grzegorz; Gajewiak, Joanna","year":2012,"journal":"The Journal of biological chemistry, 287(24), 20727-36","doi":"10.1074/jbc.M112.350462","pmid":"22518838","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The stapled conantokin-G analog conG[11-15,S(i,i+4)S(8)] demonstrated:\n\n- Potent NR2B-selective NMDA receptor antagonism: IC50 = 0.7 μM\n- Significant protection in the 6-Hz psychomotor seizure model (a model specifically designed to detect efficacy against drug-resistant epilepsy)\n- No behavioral motor toxicity (unlike native conantokin-G)\n- Enhanced helical conformation in metal-free environments (confirmed by circular dichroism and molecular modeling)\n- NMR confirmed single Z-configuration olefinic bond from ring-closing metathesis\n\nThe i,i+4 staple positioning successfully replaced the γ-carboxyglutamic acid residues' metal-chelation function while preserving pharmacological activity.","whyItMatters":"About one-third of epilepsy patients don't respond to existing medications — this is called pharmacoresistant or drug-resistant epilepsy. NMDA receptor antagonists, particularly NR2B-selective ones, are promising for these patients but have been plagued by side effects. This study shows that peptide stapling can transform a natural venom peptide into a drug candidate that is effective in a drug-resistant epilepsy model while eliminating the motor side effects that would otherwise prevent clinical use.","specificNumbers":"","methodology":"Multiple stapled analogs of conantokin-G were designed with varying staple lengths and positions along the α-helix. Peptides were synthesized using ring-closing metathesis. Structural characterization included NMR spectroscopy, circular dichroism, and molecular modeling. In vitro activity was tested in NMDA receptor antagonism assays (NR2B-containing receptors). In vivo efficacy was assessed in the 6-Hz psychomotor seizure model in mice (a validated model of pharmacoresistant epilepsy). Motor toxicity was evaluated by behavioral assessment.","limitations":"Preclinical mouse study — efficacy and safety in humans are unknown. The 6-Hz seizure model, while specifically designed for drug-resistant epilepsy, does not capture all forms of human epilepsy. Only one stapled analog showed the ideal profile (efficacy without toxicity), suggesting the optimization window is narrow. Pharmacokinetics, brain penetration, and metabolic stability were not reported. The peptide requires synthesis by ring-closing metathesis, which may pose manufacturing challenges at scale. The study is from 2012 and follow-up clinical development status is unclear."},{"rthcId":"RPEP-02041","title":"Unraveling oxyntomodulin, GLP1's enigmatic brother.","authors":"Pocai, Alessandro","year":2012,"journal":"The Journal of endocrinology, 215(3), 335-46","doi":"10.1530/JOE-12-0368","pmid":"23019069","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Oxyntomodulin (OXM) is a gut-derived peptide that acts as a dual agonist of both the GLP-1 receptor and the glucagon receptor. This review summarizes evidence that OXM injections in humans cause significant reductions in weight and appetite while increasing energy expenditure — a combination that single GLP-1 receptor agonists don't fully achieve. Although glucagon receptor activation normally raises blood sugar (potentially harmful in diabetics), the simultaneous GLP-1 receptor activation counteracts this effect. In diet-induced obese mice, OXM improved glucose tolerance. The dual agonist approach may offer enhanced weight loss and better glycemic control compared to GLP-1 agonists alone.","whyItMatters":"This review foreshadowed the dual and multi-agonist drugs now in development (like survodutide and other GLP-1/glucagon dual agonists). It laid out the scientific rationale for why combining GLP-1 and glucagon receptor activity could be more effective for obesity and diabetes than targeting GLP-1 alone — an idea that has since driven a major wave of pharmaceutical development.","specificNumbers":"","methodology":"This is a narrative review article synthesizing published research on oxyntomodulin's pharmacology, including human injection studies, mouse models of diet-induced obesity, and receptor binding data. No new experimental data were generated.","limitations":"As a review article, this does not present new experimental data. The human evidence for OXM cited was based on relatively small, short-term injection studies. The clinical translation of dual agonism was still theoretical at the time of publication, with no approved dual-agonist drugs available."},{"rthcId":"RPEP-02042","title":"Recombinant production of self-assembling β-structured peptides using SUMO as a fusion partner.","authors":"Prakash, Abhinav; Parsons, Stephen J; Kyle, Stuart; McPherson, Michael J","year":2012,"journal":"Microbial cell factories, 11, 92","doi":"10.1186/1475-2859-11-92","pmid":"22759375","tags":[],"studyType":"laboratory","evidenceStrength":"low","keyFinding":"Researchers successfully produced self-assembling β-structured peptides (the P₁₁ family) using a SUMO fusion protein system in bacteria, achieving high yields with 46–99% peptide recovery after cleavage. The recombinant peptides behaved identically to chemically synthesized versions in self-assembly and biophysical assays, demonstrating this as a viable alternative production method for hydrogel-forming peptides used in tissue engineering.","whyItMatters":"Self-assembling peptide hydrogels are promising biomaterials for tissue engineering, but chemical synthesis can be expensive and difficult to scale. This recombinant production method using bacteria could make these materials more accessible and affordable for biomedical applications.","specificNumbers":"3 peptides produced · 46–99% recovery rates · P₁₁-4 (11 amino acids) · pH 7.4 physiological conditions · 140 mM NaCl","methodology":"Laboratory study expressing SUMO-peptide fusion proteins from pET vectors in E. coli using autoinduction. Fusion proteins were purified by immobilized metal affinity chromatography, cleaved with SUMO protease in water, and recovered by reverse phase HPLC. Products were verified by electrospray mass spectrometry. Self-assembly was confirmed by circular dichroism and transmission electron microscopy.","limitations":"This is a proof-of-concept laboratory study demonstrating technical feasibility, not testing biomedical applications. Scalability beyond lab bench and cost comparisons with chemical synthesis were not addressed. The peptides are short (11 amino acids), and the approach may not generalize to all self-assembling peptide sequences."},{"rthcId":"RPEP-02043","title":"Azapeptide analogues of the growth hormone releasing peptide 6 as cluster of differentiation 36 receptor ligands with reduced affinity for the growth hormone secretagogue receptor 1a.","authors":"Proulx, Caroline; Picard, Émilie; Boeglin, Damien; Pohankova, Petra; Chemtob, Sylvain; Ong, Huy; Lubell, William D","year":2012,"journal":"Journal of medicinal chemistry, 55(14), 6502-11","doi":"10.1021/jm300557t","pmid":"22712585","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02044","title":"Peptide bicycles that inhibit the Grb2 SH2 domain.","authors":"Quartararo, Justin S; Wu, Pianpian; Kritzer, Joshua A","year":2012,"journal":"Chembiochem : a European journal of chemical biology, 13(10), 1490-6","doi":"10.1002/cbic.201200175","pmid":"22689355","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02045","title":"ACE inhibitory peptides and antioxidant peptides derived from in vitro digestion hydrolysate of hen egg white lysozyme.","authors":"Rao, Shengqi; Sun, Jun; Liu, Yuntao; Zeng, Huawei; Su, Yujie; Yang, Yanjun","year":2012,"journal":"Food chemistry, 135(3), 1245-52","doi":"10.1016/j.foodchem.2012.05.059","pmid":"22953850","tags":["food-derived-peptides"],"studyType":"in-vitro-study","evidenceStrength":"preliminary","keyFinding":"When hen egg white lysozyme was digested in a simulated gut environment, the resulting peptide fragments showed strong ACE-inhibitory activity with an IC50 of 12.6 μg/ml — meaning a very low concentration was needed to block half the activity of the blood-pressure-raising enzyme ACE. The digest also showed remarkable antioxidant activity.\n\nUsing mass spectrometry, the researchers identified 38 distinct peptides in the digest. Several of these matched the known structural requirements for ACE inhibition and antioxidant function, suggesting egg white lysozyme is a rich source of multifunctional bioactive peptides.","whyItMatters":"ACE inhibitors are one of the most widely prescribed classes of blood pressure medication. Finding natural food-derived peptides with ACE-inhibitory and antioxidant properties could lead to functional foods or supplements that support cardiovascular health through everyday diet — offering a complementary approach to pharmaceutical treatment.","specificNumbers":"IC50 = 12.6 μg/ml for ACE inhibition · 38 peptides identified · 3 kDa membrane filtration · simulated gastrointestinal digestion","methodology":"Researchers subjected hen egg white lysozyme to simulated gastrointestinal digestion (mimicking the stomach and intestine). The resulting peptide fragments were filtered through a 3 kDa membrane, and the smaller peptides that passed through were analyzed using MALDI-TOF-TOF mass spectrometry to identify individual peptide sequences. ACE-inhibitory and antioxidant activities were measured in vitro.","limitations":"This is entirely an in-vitro study — the ACE inhibition and antioxidant effects were measured in test tubes, not in living organisms. Whether these peptides survive real human digestion, get absorbed into the bloodstream, and actually lower blood pressure remains unknown. No animal or human studies were conducted."},{"rthcId":"RPEP-02046","title":"Nutrient sensing and signalling by the gut.","authors":"Rasoamanana, Rojo; Darcel, Nicolas; Fromentin, Gilles; Tomé, Daniel","year":2012,"journal":"The Proceedings of the Nutrition Society, 71(4), 446-55","doi":"10.1017/S0029665112000110","pmid":"22453062","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies specific nutrient receptors expressed on enteroendocrine cells in the gut: T1R1/T1R3, calcium-sensing receptor, and GPR93 for amino acids and protein; GPR40, GPR41, GPR43, and GPR120 for fatty acids; and T1R2/T1R3 for sugars. These receptors serve a dual function: regulating nutrient transporter expression to control absorption, and directly stimulating secretion of gastrointestinal peptides (CCK, GLP-1, PYY) into the lamina propria.\n\nThese peptide signals are transmitted to brain centers controlling feeding behavior (hypothalamus and nucleus of the solitary tract) primarily via vagal nerve afferents, forming the first signal of satiation. The review also notes that tastant compounds — not just full nutrient molecules — can trigger gut peptide secretion via chemosensory receptors on enteroendocrine cells.","whyItMatters":"The success of GLP-1 receptor agonist drugs (semaglutide, tirzepatide) for obesity has validated the therapeutic power of gut peptide signaling. This review goes upstream to the source — the nutrient receptors that naturally trigger GLP-1, CCK, and PYY release — suggesting an alternative therapeutic strategy: rather than injecting synthetic peptides, drugs could activate the gut's own nutrient-sensing receptors to enhance endogenous peptide secretion. This could potentially achieve similar appetite-suppressing effects through the body's natural satiety system.","specificNumbers":"","methodology":"This is a narrative review synthesizing research on gut nutrient sensing, receptor biology, enteroendocrine cell function, and gut-brain peptide signaling. It integrates molecular biology, receptor pharmacology, and neuroscience perspectives.","limitations":"As a 2012 review, some receptor characterizations and signaling pathway details have been refined or expanded by subsequent research. The therapeutic potential of targeting nutrient receptors in enteroendocrine cells remains largely unproven in human clinical trials. The review focuses primarily on acute satiation signaling and may not capture the full complexity of chronic appetite regulation. Species differences between animal models and humans in nutrient receptor expression and function were not extensively addressed."},{"rthcId":"RPEP-02047","title":"Satiety hormone and metabolomic response to an intermittent high energy diet differs in rats consuming long-term diets high in protein or prebiotic fiber.","authors":"Reimer, Raylene A; Maurer, Alannah D; Eller, Lindsay K; Hallam, Megan C; Shaykhutdinov, Rustem; Vogel, Hans J; Weljie, Aalim M","year":2012,"journal":"Journal of proteome research, 11(8), 4065-74","doi":"10.1021/pr300487s","pmid":"22788871","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02048","title":"Antagonists of growth hormone-releasing hormone inhibit growth of androgen-independent prostate cancer through inactivation of ERK and Akt kinases.","authors":"Rick, Ferenc G; Schally, Andrew V; Szalontay, Luca; Block, Norman L; Szepeshazi, Karoly; Nadji, Mehrdad; Zarandi, Marta; Hohla, Florian; Buchholz, Stefan; Seitz, Stephan","year":2012,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 109(5), 1655-60","doi":"10.1073/pnas.1120588109","pmid":"22307626","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02049","title":"GHRH antagonist when combined with cytotoxic agents induces S-phase arrest and additive growth inhibition of human colon cancer.","authors":"Rick, Ferenc G; Seitz, Stephan; Schally, Andrew V; Szalontay, Luca; Krishan, Awtar; Datz, Christian; Stadlmayr, Andreas; Buchholz, Stefan; Block, Norman L; Hohla, Florian","year":2012,"journal":"Cell cycle (Georgetown, Tex.), 11(22), 4203-10","doi":"10.4161/cc.22498","pmid":"23095641","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02050","title":"Direct regulation of GnRH neuron excitability by arcuate nucleus POMC and NPY neuron neuropeptides in female mice.","authors":"Roa, Juan; Herbison, Allan E","year":2012,"journal":"Endocrinology, 153(11), 5587-99","doi":"10.1210/en.2012-1470","pmid":"22948210","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Alpha-melanocyte-stimulating hormone (α-MSH) activated approximately 70% of GnRH neurons through direct postsynaptic melanocortin receptor 3 and 4 signaling. NPY had complex, receptor-specific effects: Y1 receptors suppressed GnRH neuron activity (~45% inhibited by porcine NPY), while Y4 receptors were stimulatory (~56% excited by a Y1/Y4/Y5 agonist). A small subset of GnRH neurons (~15%) was excited by CART peptide, and β-endorphin inhibited a similar proportion.\n\nAgouti-related peptide showed variable effects, inhibiting ~10% and stimulating ~25% of GnRH neurons. These findings demonstrate that metabolic-sensing neurons regulate fertility neurons through multiple neuropeptide pathways acting in parallel.","whyItMatters":"It is well known that nutritional status affects fertility — severe caloric restriction can halt menstrual cycles, for example — but the precise neural mechanisms have been unclear. This study identifies specific neuropeptide pathways that directly connect the brain's metabolic sensing neurons to the neurons controlling reproductive hormones, providing concrete molecular targets for understanding and potentially treating metabolic infertility.","specificNumbers":"","methodology":"Researchers used electrophysiology recordings on GnRH neurons in brain slices from female mice. They applied various neuropeptides and receptor-specific agonists to GnRH neurons and measured changes in neuronal firing. Selective agonists for Y1, Y2, Y4, and Y5 NPY receptors were used to identify which receptor subtypes mediate the effects on GnRH neurons.","limitations":"This study was conducted in female mice using brain slice preparations, which may not fully replicate the complexity of intact in vivo neural circuits. The results may not directly translate to humans. Additionally, the study examined individual neuropeptide effects in isolation, whereas in the living brain, multiple neuropeptides act simultaneously and may interact in ways not captured by this approach."},{"rthcId":"RPEP-02051","title":"Jack of all trades: thymosin α1 and its pleiotropy.","authors":"Romani, Luigina; Moretti, Silvia; Fallarino, Francesca; Bozza, Silvia; Ruggeri, Loredana; Casagrande, Andrea; Aversa, Franco; Bistoni, Francesco; Velardi, Andrea; Garaci, Enrico","year":2012,"journal":"Annals of the New York Academy of Sciences, 1269, 1-6","doi":"10.1111/j.1749-6632.2012.06716.x","pmid":"23045964","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02052","title":"Protegrin-1 inhibits dengue NS2B-NS3 serine protease and viral replication in MK2 cells.","authors":"Rothan, Hussin A; Abdulrahman, Ammar Y; Sasikumer, Pottayil G; Othman, Shatrah; Rahman, Noorsaadah Abd; Yusof, Rohana","year":2012,"journal":"Journal of biomedicine & biotechnology, 2012, 251482","doi":"10.1155/2012/251482","pmid":"23093838","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Protegrin-1 (PG-1) inhibited dengue NS2B-NS3 serine protease with an IC₅₀ of 11.7 μM. When tested against dengue serotype-2 (DENV-2) replication in MK2 cells, graded concentrations of PG-1 at non-toxic doses significantly reduced viral replication (p < 0.001) at 24, 48, and 72 hours post-infection.\n\nThe percentage of inhibition was significantly higher at 24 hours compared to 48 and 72 hours (p < 0.01), suggesting PG-1 is most effective in the early stages of viral replication. The peptide was synthesized with correct disulphide bond formation confirmed by LC-MS and RP-HPLC.","whyItMatters":"Dengue infects hundreds of millions of people annually and has no approved antiviral treatment. The NS2B-NS3 protease is essential for dengue virus replication and is a validated drug target. Discovering that an existing antimicrobial peptide can inhibit this enzyme opens a new avenue for peptide-based antiviral drug development against dengue.","specificNumbers":"","methodology":"PG-1 (sequence: RGGRLCYCRRRFCVCVGR) was synthesized by solid-phase peptide synthesis with disulphide bond formation and purity confirmed by LC-MS and RP-HPLC. Dengue NS2B-NS3 protease was produced as a recombinant protein in E. coli. Protease inhibition was measured by fluorescence emission of a catalyzed substrate. Antiviral activity was assessed by real-time PCR quantification of DENV-2 replication in Rhesus monkey kidney (MK2) cells at 24, 48, and 72 hours post-infection.","limitations":"This is an in vitro study using cell culture, not an animal or human study. The IC₅₀ of 11.7 μM is relatively high for a drug candidate and would likely need optimization. PG-1's effectiveness decreased over time (strongest at 24 hours), suggesting it may not provide sustained antiviral activity. Peptide stability in vivo and delivery challenges were not addressed. Only dengue serotype-2 was tested."},{"rthcId":"RPEP-02053","title":"Discovery of cyclic sulfone hydroxyethylamines as potent and selective β-site APP-cleaving enzyme 1 (BACE1) inhibitors: structure-based design and in vivo reduction of amyloid β-peptides.","authors":"Rueeger, Heinrich; Lueoend, Rainer; Rogel, Olivier; Rondeau, Jean-Michel; Möbitz, Henrik; Machauer, Rainer; Jacobson, Laura; Staufenbiel, Matthias; Desrayaud, Sandrine; Neumann, Ulf","year":2012,"journal":"Journal of medicinal chemistry, 55(7), 3364-86","doi":"10.1021/jm300069y","pmid":"22380629","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02054","title":"Peripheral mechanisms of dental pain: the role of substance P.","authors":"Sacerdote, Paola; Levrini, Luca","year":2012,"journal":"Mediators of inflammation, 2012, 951920","doi":"10.1155/2012/951920","pmid":"22474402","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02055","title":"Acromegaly caused by growth hormone releasing hormone (GHRH) secreting tumor in multiple endocrine neoplasia (MEN-1).","authors":"Saleem, Tipu Faiz M; Santhanam, Prasanna; Hamoudeh, Eyad; Hassan, Tamer; Faiz, Saba","year":2012,"journal":"The West Virginia medical journal, 108(2), 26-30","doi":null,"pmid":"22655432","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02056","title":"The anorectic effect of GLP-1 in rats is nutrient dependent.","authors":"Sandoval, Darleen; Barrera, Jason G; Stefater, Margaret A; Sisley, Stephanie; Woods, Stephen C; D'Alessio, David D; Seeley, Randy J","year":2012,"journal":"PloS one, 7(12), e51870","doi":"10.1371/journal.pone.0051870","pmid":"23284795","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02057","title":"Therapeutic potential of VIP vs PACAP in diabetes.","authors":"Sanlioglu, Ahter D; Karacay, Bahri; Balci, Mustafa Kemal; Griffith, Thomas S; Sanlioglu, Salih","year":2012,"journal":"Journal of molecular endocrinology, 49(3), R157-67","doi":"10.1530/JME-12-0156","pmid":"22991228","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02058","title":"Distributions of calcitonin gene-related peptide and substance P in the human maxillary sinus of Japanese cadavers.","authors":"Sato, Iwao; Imura, Kosuke; Miwa, Yoko; Yoshida, Shunji; Sunohara, Masataka","year":2012,"journal":"Journal of cranio-maxillo-facial surgery : official publication of the European Association for Cranio-Maxillo-Facial Surgery, 40(8), e249-52","doi":"10.1016/j.jcms.2011.10.027","pmid":"22079125","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Substance P (SP) and CGRP-positive nerve fibers were identified around large vessels of the medialis superior alveolar branches and within the floor region of the maxillary sinus. The floor region contained particularly complex branching networks of these neuropeptide-containing fibers. These findings provide an anatomical map of pain- and inflammation-mediating nerve fibers relevant to sinus floor elevation surgery.","whyItMatters":"CGRP and Substance P are key neuropeptides involved in pain, inflammation, and blood flow regulation. Knowing exactly where these nerve fibers are concentrated in the maxillary sinus helps surgeons minimize pain and inflammation during sinus floor elevation procedures — a common dental surgery performed before implant placement.","specificNumbers":"","methodology":"Whole-mount immunohistochemistry was performed on maxillary sinus tissue from male Japanese cadavers aged 80-90 years. The Schneiderian membrane (sinus lining) was examined for SP and CGRP nerve fiber distribution patterns in relation to the vascular supply.","limitations":"The study used a small number of elderly male cadavers (aged 80-90), so the neuropeptide fiber distribution may differ in younger individuals or females. Cadaver tissue may not perfectly represent living tissue neuropeptide expression. The study was descriptive/anatomical and did not measure functional aspects of these nerve fibers. Only Japanese subjects were studied."},{"rthcId":"RPEP-02059","title":"Function but not phenotype of melanoma peptide-specific CD8(+) T cells correlate with survival in a multiepitope peptide vaccine trial (ECOG 1696).","authors":"Schaefer, Carsten; Butterfield, Lisa H; Lee, Sandra; Kim, Grace G; Visus, Carmen; Albers, Andreas; Kirkwood, John M; Whiteside, Theresa L","year":2012,"journal":"International journal of cancer, 131(4), 874-84","doi":"10.1002/ijc.26481","pmid":"22021080","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02060","title":"Peptide-based approaches to treat lupus and other autoimmune diseases.","authors":"Schall, Nicolas; Page, Nicolas; Macri, Christophe; Chaloin, Olivier; Briand, Jean-Paul; Muller, Sylviane","year":2012,"journal":"Journal of autoimmunity, 39(3), 143-53","doi":"10.1016/j.jaut.2012.05.016","pmid":"22727561","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02061","title":"Comparative syntheses of peptides and peptide thioesters derived from mouse and human prion proteins.","authors":"Sebestík, Jaroslav; Zawada, Zbigniew; Safařík, Martin; Hlaváček, Jan","year":2012,"journal":"Amino acids, 43(3), 1297-309","doi":"10.1007/s00726-011-1203-9","pmid":"22212592","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02062","title":"Ghrelin and the brain-gut axis as a pharmacological target for appetite control.","authors":"Seim, Inge; El-Salhy, Magdy; Hausken, Trygve; Gundersen, Doris; Chopin, Lisa","year":2012,"journal":"Current pharmaceutical design, 18(6), 768-75","doi":null,"pmid":"22236122","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02063","title":"Thymosin α1 as a stimulatory agent of innate cell-mediated immune response.","authors":"Serafino, Annalucia; Pierimarchi, Pasquale; Pica, Francesca; Andreola, Federica; Gaziano, Roberta; Moroni, Noemi; Zonfrillo, Manuela; Sinibaldi-Vallebona, Paola; Garaci, Enrico","year":2012,"journal":"Annals of the New York Academy of Sciences, 1270, 13-20","doi":"10.1111/j.1749-6632.2012.06707.x","pmid":"23050812","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02064","title":"Effect of PhoP-PhoQ activation by broad repertoire of antimicrobial peptides on bacterial resistance.","authors":"Shprung, Tal; Peleg, Adi; Rosenfeld, Yosef; Trieu-Cuot, Patrick; Shai, Yechiel","year":2012,"journal":"The Journal of biological chemistry, 287(7), 4544-51","doi":"10.1074/jbc.M111.278523","pmid":"22158870","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02065","title":"Pharmacological characterization of the ghrelin receptor mediating its inhibitory action on inflammatory pain in rats.","authors":"Sibilia, Valeria; Pagani, Francesca; Mrak, Emanuela; Dieci, Elisa; Tulipano, Giovanni; Ferrucci, Francesco","year":2012,"journal":"Amino acids, 43(4), 1751-9","doi":null,"pmid":"22407485","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02066","title":"GHRH antagonist inhibits focal adhesion kinase (FAK) and decreases expression of vascular endothelial growth factor (VEGF) in human lung cancer cells in vitro.","authors":"Siejka, Agnieszka; Barabutis, Nektarios; Schally, Andrew V","year":2012,"journal":"Peptides, 37(1), 63-8","doi":"10.1016/j.peptides.2012.07.010","pmid":"22819774","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02067","title":"Focus on ulcerative colitis: stable gastric pentadecapeptide BPC 157.","authors":"Sikiric, P; Seiwerth, S; Rucman, R; Turkovic, B; Rokotov, D S; Brcic, L; Sever, M; Klicek, R; Radic, B; Drmic, D; Ilic, S; Kolenc, D; Stambolija, V; Zoricic, Z; Vrcic, H; Sebecic, B","year":2012,"journal":"Current medicinal chemistry, 19(1), 126-32","doi":null,"pmid":"22300085","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02068","title":"Enhanced leishmanicidal activity of cryptopeptide chimeras from the active N1 domain of bovine lactoferrin.","authors":"Silva, Tânia; Abengózar, María Ángeles; Fernández-Reyes, María; Andreu, David; Nazmi, Kamran; Bolscher, Jan G M; Bastos, Margarida; Rivas, Luis","year":2012,"journal":"Amino acids, 43(6), 2265-77","doi":"10.1007/s00726-012-1304-0","pmid":"22543751","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02069","title":"Structure based design and synthesis of peptide inhibitor of human LOX-12: in vitro and in vivo analysis of a novel therapeutic agent for breast cancer.","authors":"Singh, Abhay Kumar; Singh, Ratnakar; Naz, Farhat; Chauhan, Shyam Singh; Dinda, Amit; Shukla, Abhay Anand; Gill, Kamaldeep; Kapoor, Vaishali; Dey, Sharmistha","year":2012,"journal":"PloS one, 7(2), e32521","doi":"10.1371/journal.pone.0032521","pmid":"22384268","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02070","title":"Role of ghrelin in food reward: impact of ghrelin on sucrose self-administration and mesolimbic dopamine and acetylcholine receptor gene expression.","authors":"Skibicka, Karolina P; Hansson, Caroline; Egecioglu, Emil; Dickson, Suzanne L","year":2012,"journal":"Addiction biology, 17(1), 95-107","doi":"10.1111/j.1369-1600.2010.00294.x","pmid":"21309956","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02071","title":"Sensing the environment: regulation of local and global homeostasis by the skin's neuroendocrine system.","authors":"Slominski, Andrzej T; Zmijewski, Michal A; Skobowiat, Cezary; Zbytek, Blazej; Slominski, Radomir M; Steketee, Jeffery D","year":2012,"journal":"Advances in anatomy, embryology, and cell biology, 212, v, vii, 1-115","doi":null,"pmid":"22894052","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02072","title":"The role of kisspeptin and gonadotropin inhibitory hormone in the seasonal regulation of reproduction in sheep.","authors":"Smith, J T","year":2012,"journal":"Domestic animal endocrinology, 43(2), 75-84","doi":"10.1016/j.domaniend.2011.11.003","pmid":"22177698","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02073","title":"Potential applications of vasoactive intestinal Peptide-based therapies on transplantation.","authors":"Souza-Moreira, Luciana; Delgado-Maroto, Virginia; Delgado, Mario","year":2012,"journal":"Endocrine, metabolic & immune disorders drug targets, 12(4), 333-43","doi":null,"pmid":"23094830","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02074","title":"Incorporating glucagon-like peptide-1 receptor agonists into clinical practice.","authors":"Spellman, Craig W","year":2012,"journal":"The Journal of the American Osteopathic Association, 112(1 Suppl 1), S7-15","doi":null,"pmid":"22267302","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Both exenatide and liraglutide improved glycemic control as monotherapy and in combination with oral agents, providing additive effects in dual and triple therapy regimens. In head-to-head clinical trials, liraglutide achieved greater reductions in HbA1c and fasting plasma glucose, while exenatide had greater effects on postprandial glucose levels.\n\nBoth agents demonstrated statistically significant weight reduction and small beneficial effects on blood pressure, with unchanged lipid profiles. The review positioned GLP-1 receptor agonists as a treatment option that could address multiple cardiometabolic parameters beyond glycemic control alone.","whyItMatters":"This review captures the GLP-1 receptor agonist class at a pivotal early moment — when only two agents existed and their place in diabetes treatment algorithms was still being established. The clinical advantages identified here (glycemic control plus weight loss plus blood pressure benefits) foreshadowed the class's massive expansion into obesity treatment and cardiovascular protection over the following decade.","specificNumbers":"","methodology":"Narrative review of clinical trial data for exenatide and liraglutide in type 2 diabetes, covering efficacy (glycemic control, weight, blood pressure, lipids), safety, contraindications, and placement in treatment algorithms.","limitations":"As a 2012 review, this covers only first-generation GLP-1 agonists (exenatide and liraglutide) and does not reflect the dramatically expanded evidence base and newer agents available today. The review is by a single author without systematic methodology. Long-term cardiovascular outcome data, which later became the class's strongest selling point, were not yet available."},{"rthcId":"RPEP-02075","title":"Screening of soy and milk protein hydrolysates for their ability to activate the CCK1 receptor.","authors":"Staljanssens, Dorien; Van Camp, John; Billiet, Annelies; De Meyer, Tim; Al Shukor, Nadin; De Vos, Winnok H; Smagghe, Guy","year":2012,"journal":"Peptides, 34(1), 226-31","doi":"10.1016/j.peptides.2011.11.019","pmid":"22138720","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02076","title":"Inhibitory effects of antagonists of growth hormone releasing hormone on experimental prostate cancers are associated with upregulation of wild-type p53 and decrease in p21 and mutant p53 proteins.","authors":"Stangelberger, Anton; Schally, Andrew V; Rick, Ferenc G; Varga, Jozsef L; Baker, Benjamin; Zarandi, Marta; Halmos, Gabor","year":2012,"journal":"The Prostate, 72(5), 555-65","doi":"10.1002/pros.21458","pmid":"21796649","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02077","title":"Reduction in visceral adiposity is associated with an improved metabolic profile in HIV-infected patients receiving tesamorelin.","authors":"Stanley, Takara L; Falutz, Julian; Marsolais, Christian; Morin, Josée; Soulban, Graziella; Mamputu, Jean-Claude; Assaad, Hani; Turner, Ralph; Grinspoon, Steven K","year":2012,"journal":"Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 54(11), 1642-51","doi":"10.1093/cid/cis251","pmid":"22495074","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02078","title":"Pentadecapeptide BPC 157 reduces bleeding time and thrombocytopenia after amputation in rats treated with heparin, warfarin or aspirin.","authors":"Stupnisek, Mirjana; Franjic, Sandra; Drmic, Domagoj; Hrelec, Masa; Kolenc, Danijela; Radic, Bozo; Bojic, Davor; Vcev, Aleksandar; Seiwerth, Sven; Sikiric, Predrag","year":2012,"journal":"Thrombosis research, 129(5), 652-9","doi":"10.1016/j.thromres.2011.07.035","pmid":"21840572","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02079","title":"miR-203 regulates nociceptive sensitization after incision by controlling phospholipase A2 activating protein expression.","authors":"Sun, Yuan; Li, Xiang-Qi; Sahbaie, Peyman; Shi, Xiao-You; Li, Wen-Wu; Liang, De-Yong; Clark, J David","year":2012,"journal":"Anesthesiology, 117(3), 626-38","doi":"10.1097/ALN.0b013e31826571aa","pmid":"22846677","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02080","title":"Sensation of abdominal pain induced by peritoneal carcinomatosis is accompanied by changes in the expression of substance P and μ-opioid receptors in the spinal cord of mice.","authors":"Suzuki, Masami; Narita, Minoru; Hasegawa, Minami; Furuta, Sadayoshi; Kawamata, Tomoyuki; Ashikawa, Maho; Miyano, Kanako; Yanagihara, Kazuyoshi; Chiwaki, Fumiko; Ochiya, Takahiro; Suzuki, Tsutomu; Matoba, Motohiro; Sasaki, Hiroki; Uezono, Yasuhito","year":2012,"journal":"Anesthesiology, 117(4), 847-56","doi":null,"pmid":"22913923","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02081","title":"Liposomal delivery of proteins and peptides.","authors":"Swaminathan, Janani; Ehrhardt, Carsten","year":2012,"journal":"Expert opinion on drug delivery, 9(12), 1489-503","doi":"10.1517/17425247.2012.735658","pmid":"23092138","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02082","title":"Mice deficient in pituitary adenylate cyclase activating polypeptide (PACAP) are more susceptible to retinal ischemic injury in vivo.","authors":"Szabadfi, K; Atlasz, T; Kiss, P; Danyadi, B; Tamas, A; Helyes, Zs; Hashimoto, H; Shintani, N; Baba, A; Toth, G; Gabriel, R; Reglodi, D","year":2012,"journal":"Neurotoxicity research, 21(1), 41-8","doi":"10.1007/s12640-011-9254-y","pmid":"21717232","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02083","title":"Protective effects of the neuropeptide PACAP in diabetic retinopathy.","authors":"Szabadfi, Krisztina; Atlasz, Tamas; Kiss, Peter; Reglodi, Dora; Szabo, Aliz; Kovacs, Krisztina; Szalontai, Balint; Setalo, Gyorgy; Banki, Eszter; Csanaky, Katalin; Tamas, Andrea; Gabriel, Robert","year":2012,"journal":"Cell and tissue research, 348(1), 37-46","doi":"10.1007/s00441-012-1349-0","pmid":"22350850","tags":["neuropeptides"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"The neuropeptide PACAP (pituitary adenylate cyclase activating polypeptide) significantly protected the retina from diabetes-induced damage when injected into the eyes of diabetic rats. In untreated diabetic retinas, cone photoreceptors degenerated, dopaminergic nerve cells were lost, ganglion cell numbers declined, and glial cells showed stress responses.\n\nPACAP treatment reversed these structural changes — it preserved cone photoreceptors and their outer segments, maintained ganglion cell numbers, and upregulated the PAC1 receptor and tyrosine hydroxylase (an enzyme critical for dopamine production). The protection appears to work through PACAP's PAC1 receptor.","whyItMatters":"Diabetic retinopathy is the leading cause of blindness in working-age adults, and current treatments focus on late-stage vascular damage. This study shows that PACAP can protect retinal neurons early in the disease process — before the blood vessel problems become severe. If neuropeptide-based therapies could be developed for the retina, they might preserve vision by preventing the neuronal damage that precedes and accompanies diabetic retinopathy.","specificNumbers":"100 pmol PACAP per intravitreal injection · 3 injections over 1 week · 3-week diabetes model · Cone photoreceptors, ganglion cells, and dopaminergic cells all protected · PAC1 receptor and tyrosine hydroxylase upregulated","methodology":"Diabetes was induced in Wistar rats with streptozotocin injection. PACAP (100 pmol) was injected directly into one eye three times during the last week of a 3-week period. Retinas were analyzed using histology, immunohistochemistry (single/double labeling and whole-mount), quantitative RT-PCR, and Western blotting to assess structural and molecular changes.","limitations":"This was a short-term (3-week) rat model of diabetes, which doesn't fully replicate the years-long progression of human diabetic retinopathy. Intravitreal injection is invasive and the study didn't test less invasive delivery methods. Specific quantitative data on cell counts and protein levels are in the full paper but not the abstract. No functional vision testing was reported."},{"rthcId":"RPEP-02084","title":"Inhibitory effects of GHRH antagonists on human GH-secreting adenoma tissue.","authors":"Szalontay, Luca; Benveniste, Ronald J; Schally, Andrew V; Vidaurre, Irving; Nadji, Mehrdad; Zarandi, Marta; Block, Norman L; Kovacs, Magdolna","year":2012,"journal":"Neuroendocrinology, 96(1), 81-8","doi":"10.1159/000335989","pmid":"22377963","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GHRH antagonists MZ-4-71 and JV-1-36 effectively blocked GHRH-stimulated growth hormone secretion from human pituitary adenoma cells. When tumor cells were exposed to GHRH pulses, GH levels rose 3- to 5-fold above baseline. Both antagonists completely prevented this stimulatory response.\n\nImportantly, neither GHRH antagonist affected baseline GH secretion, indicating the tumor cells were not producing GHRH themselves in an autocrine loop — they were responding to external GHRH signals. The somatostatin analog RC-160 showed similar inhibitory effects and was more potent than natural somatostatin-14. The study also confirmed abundant expression of the GHRH receptor and its splice variant SV1 in the adenoma tissue.","whyItMatters":"Acromegaly is currently treated with surgery and somatostatin analogs, but not all patients respond adequately. GHRH antagonists represent a fundamentally different approach — blocking the upstream signal that drives growth hormone overproduction rather than suppressing GH release at the somatostatin receptor. This study provided the missing proof that GHRH antagonists actually work on human pituitary adenoma tissue, not just in animal models.","specificNumbers":"","methodology":"Researchers obtained pituitary tumor tissue from a patient with a GH-secreting adenoma during surgery. They set up a superfusion system to test drug effects on living tumor cells. Using Western blot and immunohistochemistry, they confirmed the tumor expressed GHRH receptors. They then measured GH secretion in response to GHRH pulses alone, GHRH with GHRH antagonists, and GHRH with somatostatin or its analog RC-160.","limitations":"This was an in vitro study using tissue from a single patient's tumor, so results may not generalize to all GH-secreting adenomas. The superfusion system, while useful for measuring acute hormone responses, doesn't replicate the complex in vivo environment. No dose-response data or IC50 values were reported in the abstract. The drugs tested are experimental and have not progressed to clinical trials for acromegaly."},{"rthcId":"RPEP-02085","title":"Dietary fiber, gut peptides, and adipocytokines.","authors":"Sánchez, David; Miguel, Marta; Aleixandre, Amaya","year":2012,"journal":"Journal of medicinal food, 15(3), 223-30","doi":"10.1089/jmf.2011.0072","pmid":"22181071","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02086","title":"Dietary supplementation with bovine lactoferrampin-lactoferricin produced by Pichia pastoris fed-batch fermentation affects intestinal microflora in weaned piglets.","authors":"Tang, Xiang-Shan; Shao, Hua; Li, Tie-Jun; Tang, Zhi-Ru; Huang, Rui-Ling; Wang, Sheng-Ping; Kong, Xiang-Feng; Wu, Xin; Yin, Yu-Long","year":2012,"journal":"Applied biochemistry and biotechnology, 168(4), 887-98","doi":"10.1007/s12010-012-9827-0","pmid":"22923175","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02087","title":"Expression, purification, and antibacterial activity of bovine lactoferrampin-lactoferricin in Pichia pastoris.","authors":"Tang, Xiang-Shan; Tang, Zhi-Ru; Wang, Sheng-Ping; Feng, Ze-Meng; Zhou, Dong; Li, Tie-Jun; Yin, Yu-Long","year":2012,"journal":"Applied biochemistry and biotechnology, 166(3), 640-51","doi":"10.1007/s12010-011-9455-0","pmid":"22109740","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02088","title":"Radiolabeled RGD peptides as integrin alpha(v)beta3-targeted PET tracers.","authors":"Tateishi, U; Oka, T; Inoue, T","year":2012,"journal":"Current medicinal chemistry, 19(20), 3301-9","doi":null,"pmid":"22664242","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02089","title":"Energy expenditure: role of orexin.","authors":"Teske, Jennifer A; Mavanji, Vijayakumar","year":2012,"journal":"Vitamins and hormones, 89, 91-109","doi":"10.1016/B978-0-12-394623-2.00006-8","pmid":"22640610","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02090","title":"Immunoaffinity purification of peptide hormones prior to liquid chromatography-mass spectrometry in doping controls.","authors":"Thomas, Andreas; Schänzer, Wilhelm; Delahaut, Philippe; Thevis, Mario","year":2012,"journal":"Methods (San Diego, Calif.), 56(2), 230-5","doi":"10.1016/j.ymeth.2011.08.009","pmid":"21871962","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02091","title":"Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2.","authors":"Tolhurst, Gwen; Heffron, Helen; Lam, Yu Shan; Parker, Helen E; Habib, Abdella M; Diakogiannaki, Eleftheria; Cameron, Jennifer; Grosse, Johannes; Reimann, Frank; Gribble, Fiona M","year":2012,"journal":"Diabetes, 61(2), 364-71","doi":"10.2337/db11-1019","pmid":"22190648","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02092","title":"Novel domain-selective ACE-inhibiting activity of synthetic growth hormone secretagogues.","authors":"Torsello, Antonio; Bresciani, Elena; Ravelli, Monica; Rizzi, Laura; Bulgarelli, Ilaria; Ricci, Giorgio; Ghiazza, Barbara; Del Puppo, Marina; Mainini, Veronica; Omeljaniuk, Robert J; Tamiazzo, Laura; Mancia, Giuseppe; Magni, Fulvio; Locatelli, Vittorio","year":2012,"journal":"Pharmacological research, 66(4), 317-24","doi":"10.1016/j.phrs.2012.06.006","pmid":"22732396","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02093","title":"Thymosin α1 continues to show promise as an enhancer for vaccine response.","authors":"Tuthill, Cynthia; Rios, Israel; De Rosa, Alfonso; Camerini, Roberto","year":2012,"journal":"Annals of the New York Academy of Sciences, 1270, 21-7","doi":"10.1111/j.1749-6632.2012.06680.x","pmid":"23050813","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02094","title":"New insights into the neuroanatomical distribution and phylogeny of opioids and POMC-derived peptides in fish.","authors":"Vallarino, Mauro; d'Amora, Marta; Dores, Robert M","year":2012,"journal":"General and comparative endocrinology, 177(3), 338-47","doi":"10.1016/j.ygcen.2012.04.014","pmid":"22575795","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02095","title":"GLP1 and cancer: friend or foe?","authors":"Vangoitsenhoven, Roman; Mathieu, Chantal; Van der Schueren, Bart","year":2012,"journal":"Endocrine-related cancer, 19(5), F77-88","doi":"10.1530/ERC-12-0111","pmid":"22691625","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02096","title":"The influence of peptide impurity profiles on functional tissue-organ bath response: the 11-mer peptide INSL6[151-161] case.","authors":"Verbeken, Mathieu; Wynendaele, Evelien; Lefebvre, Romain A; Goossens, Els; Spiegeleer, Bart De","year":2012,"journal":"Analytical biochemistry, 421(2), 547-55","doi":"10.1016/j.ab.2011.09.031","pmid":"22033292","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Crude INSL6[151-161] peptide (~70% purity) triggered contractile responses in guinea pig ileum smooth muscle preparations. However, when the same peptide was purified to ≥95% purity, it showed no biological activity whatsoever in the same model.\n\nCrude peptide materials from multiple suppliers (50-80% purity) all produced false-positive results, confirming that the activity came from synthesis by-products rather than the target peptide. This demonstrates that impurity profiles from peptide synthesis can produce entirely misleading biological conclusions — a critical quality control issue for the peptide research field.","whyItMatters":"This study raises a red flag for the entire peptide research field. During early-stage drug discovery and basic research, scientists frequently use crude-purity peptides because they're cheaper and faster to obtain. But if impurities can produce biological effects that look like they come from the peptide, researchers could pursue dead-end drug candidates or draw wrong conclusions about peptide biology. The finding argues for stricter quality control standards in peptide research from the earliest stages.","specificNumbers":"","methodology":"Researchers tested INSL6[151-161] peptide in guinea pig ileum longitudinal smooth muscle preparations using tissue-organ baths — a classical pharmacological assay. They compared crude peptide material (~70% purity) against highly purified peptide (≥95% purity). To confirm their finding, they tested crude materials from multiple commercial suppliers with purities ranging from 50% to 80%. HPLC and mass spectrometry were used to characterize the impurity profiles.","limitations":"Only one peptide sequence (INSL6[151-161]) was tested, so the frequency of this problem across other peptide sequences is unknown. The specific impurities responsible for the false-positive activity were not fully identified. The tissue bath assay is a classical but relatively crude pharmacological test — whether impurity-driven false positives occur with more modern cell-based assays was not assessed."},{"rthcId":"RPEP-02097","title":"Molecular engineering of short half-life small peptides (VIP, αMSH and γ₃MSH) fused to latency-associated peptide results in improved anti-inflammatory therapeutics.","authors":"Vessillier, Sandrine; Adams, Gill; Montero-Melendez, Trinidad; Jones, Rita; Seed, Michael; Perretti, Mauro; Chernajovsky, Yuti","year":2012,"journal":"Annals of the rheumatic diseases, 71(1), 143-9","doi":"10.1136/annrheumdis-2011-200100","pmid":"21998117","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02098","title":"NMR structural studies of thymosin α1 and β-thymosins.","authors":"Volk, David E; Tuthill, Cynthia W; Elizondo-Riojas, Miguel-Angel; Gorenstein, David G","year":2012,"journal":"Annals of the New York Academy of Sciences, 1270, 73-8","doi":"10.1111/j.1749-6632.2012.06656.x","pmid":"23050820","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02099","title":"Glucagon-like peptides 1 and 2 and vasoactive intestinal peptide are neuroprotective on cultured and mast cell co-cultured rat myenteric neurons.","authors":"Voss, Ulrikke; Sand, Elin; Hellström, Per M; Ekblad, Eva","year":2012,"journal":"BMC gastroenterology, 12, 30","doi":"10.1186/1471-230X-12-30","pmid":"22463807","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02100","title":"Functionalized self-assembling peptide nanofiber hydrogel as a scaffold for rabbit nucleus pulposus cells.","authors":"Wang, Baichuan; Wu, Yongchao; Shao, Zengwu; Yang, Shuhua; Che, Biao; Sun, Caixia; Ma, Zhilin; Zhang, Yannan","year":2012,"journal":"Journal of biomedical materials research. Part A, 100(3), 646-53","doi":"10.1002/jbm.a.33300","pmid":"22213420","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02101","title":"Inhibition of GHRH aggravated acetaminophen-induced acute mice liver injury through GH/IGF-I axis.","authors":"Wang, Tao; Hai, Jie; Chen, Xuehui; Peng, Hua; Zhang, He; Li, Lake; Zhang, Qinggui","year":2012,"journal":"Endocrine journal, 59(7), 579-87","doi":null,"pmid":"22572547","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02102","title":"Keratinocyte expression of inflammatory mediators plays a crucial role in substance P-induced acute and chronic pain.","authors":"Wei, Tzuping; Guo, Tian-Zhi; Li, Wen-Wu; Hou, Saiyun; Kingery, Wade S; Clark, John David","year":2012,"journal":"Journal of neuroinflammation, 9, 181","doi":null,"pmid":"22824437","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Intradermal injection of Substance P in normal rats induced mechanical allodynia (pain from light touch), warmth, edema, and upregulation of inflammatory mediators TNF-α, IL-1β, IL-6, and NGF in hindpaw skin. The NK1 receptor antagonist LY303870 attenuated allodynia, hindpaw unweighting, warmth, edema, cytokine expression, and epidermal thickening after fracture. Anti-NGF antibody blocked SP-induced pain but not warmth or edema, indicating NGF mediates the pain component specifically. LY303870 had no effect on bone microarchitecture, showing SP/NK1 signaling drives nociceptive and vascular but not skeletal components of CRPS.","whyItMatters":"CRPS is a debilitating chronic pain condition with limited treatment options. Understanding that Substance P and its NK1 receptor drive specific components of the disease — pain and vascular changes but not bone loss — could help develop targeted therapies that address the right pathways rather than treating all symptoms with a single approach.","specificNumbers":"","methodology":"Researchers used a rat tibial fracture/cast immobilization model of CRPS. They injected Substance P intradermally and measured pain responses, paw temperature, thickness, and tissue levels of inflammatory mediators over 72 hours. The NK1 antagonist LY303870 was given intraperitoneally to fracture rats. BrdU incorporation measured cell proliferation, and micro-CT assessed bone structure.","limitations":"This was an animal study using a rat fracture model, which may not fully replicate human CRPS. Only male rats were used. The NK1 antagonist was given systemically, so the specific contribution of peripheral versus central NK1 receptors could not be determined. The 72-hour observation window may not capture long-term effects."},{"rthcId":"RPEP-02103","title":"Inconsistencies in the assessment of food intake.","authors":"Woods, Stephen C; Langhans, Wolfgang","year":2012,"journal":"American journal of physiology. Endocrinology and metabolism, 303(12), E1408-18","doi":"10.1152/ajpendo.00415.2012","pmid":"23074241","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02104","title":"New agonist- and antagonist-based treatment approaches for advanced prostate cancer.","authors":"Xu, Y; Jiang, Y F; Wu, B","year":2012,"journal":"The Journal of international medical research, 40(4), 1217-26","doi":null,"pmid":"22971474","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02105","title":"Neurohormones, rikkunshito and hypothalamic neurons interactively control appetite and anorexia.","authors":"Yada, Toshihiko; Kohno, Daisuke; Maejima, Yuko; Sedbazar, Udval; Arai, Takeshi; Toriya, Masako; Maekawa, Fumihiko; Kurita, Hedeharu; Niijima, Akira; Yakabi, Koji","year":2012,"journal":"Current pharmaceutical design, 18(31), 4854-64","doi":null,"pmid":"22632865","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02106","title":"GHRP-6 mimics ghrelin-induced stimulation of food intake and suppression of locomotor activity in goldfish.","authors":"Yahashi, Satowa; Kang, Ki Sung; Kaiya, Hiroyuki; Matsuda, Kouhei","year":2012,"journal":"Peptides, 34(2), 324-8","doi":"10.1016/j.peptides.2012.01.025","pmid":"22349352","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02107","title":"Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus.","authors":"Yan, Huan; Zhong, Guocai; Xu, Guangwei; He, Wenhui; Jing, Zhiyi; Gao, Zhenchao; Huang, Yi; Qi, Yonghe; Peng, Bo; Wang, Haimin; Fu, Liran; Song, Mei; Chen, Pan; Gao, Wenqing; Ren, Bijie; Sun, Yinyan; Cai, Tao; Feng, Xiaofeng; Sui, Jianhua; Li, Wenhui","year":2012,"journal":"eLife, 1, e00049","doi":"10.7554/eLife.00049","pmid":"23150796","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02108","title":"Biophysical properties and supramolecular structure of self-assembled liposome/ε-peptide/DNA nanoparticles: correlation with gene delivery.","authors":"Yan, Jiang; Korolev, Nikolay; Eom, Khee Dong; Tam, James P; Nordenskiöld, Lars","year":2012,"journal":"Biomacromolecules, 13(1), 124-31","doi":"10.1021/bm201359r","pmid":"22066663","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Self-assembled nanoparticles combining ε-oligo(L-lysine) peptides with the cationic lipid DOTAP and plasmid DNA achieved transfection efficiency that exceeded DOTAP alone, without a significant increase in cytotoxicity.\n\nHigh transfection efficiency correlated with a zeta potential above +20 mV and a particle size below 500 nm. Synchrotron small-angle X-ray scattering confirmed the complexes formed ordered lamellar (layered) supramolecular structures, suggesting that the structural organization contributes to their gene-delivery performance.","whyItMatters":"Safe and effective gene delivery remains one of the biggest challenges in gene therapy. Viral vectors work well but carry safety risks. This study shows that simple, biodegradable peptides can be combined with lipids to create non-toxic nanoparticles that outperform the lipid alone — offering a modular, tunable platform for non-viral gene delivery.","specificNumbers":"","methodology":"The researchers synthesized ε-oligo(L-lysine) peptides via solid-phase synthesis, creating branched variants with arginine and histidine side chains. These peptides were combined with the cationic lipid DOTAP and plasmid DNA to form nanoparticles. The team measured particle size and surface charge (zeta potential), examined supramolecular structure using synchrotron small-angle X-ray scattering (SAXS), and tested gene delivery efficiency and cytotoxicity in HeLa cells in vitro.","limitations":"The study was conducted entirely in vitro using HeLa cells, so it is unknown whether these nanoparticles would perform similarly in living organisms. The specific gene expression levels and how they compare to established commercial transfection agents were not detailed. Long-term stability and biodistribution of the nanoparticles were not assessed."},{"rthcId":"RPEP-02109","title":"Effect of thymosin alpha-1 on subpopulations of Th1, Th2, Th17, and regulatory T cells (Tregs) in vitro.","authors":"Yang, Xia; Qian, Feng; He, Hai-Yang; Liu, Kai-Jun; Lan, Yuan-Zhi; Ni, Bing; Tian, Yi; Fu, Xiao-Lan; Zhang, Ji; Shen, Zi-Gang; Li, Jian; Yin, Yi; Li, Jin-Tao; Wu, Yu-Zhang","year":2012,"journal":"Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas, 45(1), 25-32","doi":null,"pmid":"22245858","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02110","title":"Regulation of peripheral clock to oscillation of substance P contributes to circadian inflammatory pain.","authors":"Zhang, Jing; Li, Huili; Teng, Huajing; Zhang, Ting; Luo, Yonglun; Zhao, Mei; Li, Yun-Qing; Sun, Zhong Sheng","year":2012,"journal":"Anesthesiology, 117(1), 149-60","doi":"10.1097/ALN.0b013e31825b4fc1","pmid":"22634872","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The Substance P gene Tac1 oscillates in dorsal root ganglion (DRG) neurons under transcriptional regulation by BMAL1:CLOCK clock gene heterodimers. This produces rhythmic Substance P protein expression in the spinal dorsal horn. Formalin-induced inflammatory pain responses in mice (n=48) followed the same circadian rhythm as Substance P expression. Blocking the SP-NK1R pathway (n=70) abolished the circadian pain rhythm. Clock gene deletion mutations disrupted both Substance P oscillation and behavioral pain rhythms, confirming the causal chain from peripheral clock → Substance P oscillation → circadian inflammatory pain.","whyItMatters":"Many inflammatory conditions and chronic pain syndromes show time-of-day variation in severity. Understanding that Substance P — a key pain neuropeptide — is under circadian clock control provides a molecular explanation for daily pain fluctuations and suggests that timing of pain medication could be optimized based on the body's neuropeptide rhythms (chronotherapy).","specificNumbers":"","methodology":"Researchers used behavioral pain observation, real-time PCR, luciferase reporter assays, chromatin immunoprecipitation, and immunohistochemistry in C57BL mice. They assessed Tac1 gene oscillation in DRG (n=36) and spinal dorsal horn, measured formalin-induced nociceptive responses across the circadian cycle (n=48), tested NK1R pathway blockade effects on pain rhythms (n=70), and examined clock gene mutant mice.","limitations":"The study was conducted in mice, and circadian pain patterns in humans may differ due to different activity cycles (humans are diurnal, mice are nocturnal). Only formalin-induced inflammatory pain was tested; other pain types may have different circadian mechanisms. The study did not assess whether chronotherapy based on SP rhythms could improve clinical pain outcomes."},{"rthcId":"RPEP-02111","title":"The role of NPY and ghrelin in anorexia nervosa.","authors":"Zhang, Lei; Yagi, Miyuki; Herzog, Herbert","year":2012,"journal":"Current pharmaceutical design, 18(31), 4766-78","doi":null,"pmid":"22632858","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02112","title":"Oleic acid and glucose regulate glucagon-like peptide 1 receptor expression in a rat pancreatic ductal cell line.","authors":"Zhang, Leshuai W; McMahon Tobin, Grainne A; Rouse, Rodney L","year":2012,"journal":"Toxicology and applied pharmacology, 264(2), 274-83","doi":"10.1016/j.taap.2012.08.008","pmid":"22925809","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02113","title":"Neuropeptide S promotes wakefulness through activation of the posterior hypothalamic histaminergic and orexinergic neurons.","authors":"Zhao, P; Shao, Y F; Zhang, M; Fan, K; Kong, X P; Wang, R; Hou, Y P","year":2012,"journal":"Neuroscience, 207, 218-26","doi":"10.1016/j.neuroscience.2012.01.022","pmid":"22300983","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02114","title":"Dynamic PET and Optical Imaging and Compartment Modeling using a Dual-labeled Cyclic RGD Peptide Probe.","authors":"Zhu, Lei; Guo, Ning; Li, Quanzheng; Ma, Ying; Jacboson, Orit; Lee, Seulki; Choi, Hak Soo; Mansfield, James R; Niu, Gang; Chen, Xiaoyuan","year":2012,"journal":"Theranostics, 2(8), 746-56","doi":"10.7150/thno.4762","pmid":"22916074","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02115","title":"Acheson 2013 Oxytocin Extinction Recall","authors":"","year":2013,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02116","title":"Busby 2013 Pharmacologic Properties Metabolism And","authors":"","year":2013,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02117","title":"Cryer 2013 Hypoglycemia Unawareness","authors":"","year":2013,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02118","title":"Prognostic value of multiple emerging biomarkers in cardiovascular risk prediction in patients with stable cardiovascular disease.","authors":"Ahluwalia, Namanjeet; Blacher, Jacques; Szabo de Edelenyi, Fabien; Faure, Patrice; Julia, Chantal; Hercberg, Serge; Galan, Pilar","year":2013,"journal":"Atherosclerosis, 228(2), 478-84","doi":"10.1016/j.atherosclerosis.2013.03.017","pmid":"23582589","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02119","title":"The ghrelin receptors (GHS-R1a and GHS-R1b).","authors":"Albarrán-Zeckler, Rosie G; Smith, Roy G","year":2013,"journal":"Endocrine development, 25, 5-15","doi":"10.1159/000346042","pmid":"23652387","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review covers the ghrelin receptor GHS-R1a from discovery to therapeutic potential:\n\n- GHS-R1a was expression-cloned at MERCK laboratories in the early 1990s using synthetic GH secretagogue molecules\n- The receptor is expressed in the brain and throughout the body\n- Its endogenous ligand, the peptide hormone ghrelin, regulates metabolism, neurotransmission, and behavior\n- Multiple GHS-R1a agonists and antagonists are available, with some showing promising clinical results\n- A second receptor form (GHS-R1b) also exists, though its function is less well characterized\n- Rodent studies have revealed potential roles for receptor modulation in obesity, glucose homeostasis, and other conditions","whyItMatters":"The ghrelin receptor sits at the crossroads of hunger, metabolism, and brain function. Understanding how to pharmacologically manipulate this receptor could lead to treatments for obesity, cachexia (wasting), growth hormone deficiency, and potentially neurological conditions — making it one of the most versatile peptide hormone drug targets.","specificNumbers":"","methodology":"This is a book chapter-style review synthesizing the literature on ghrelin receptor biology, pharmacology, and therapeutic targeting from the receptor's discovery through 2013.","limitations":"As a 2013 review chapter, it does not include more recent discoveries about ghrelin receptor signaling complexity, biased agonism, or receptor dimerization. Clinical trial results available at the time were limited. The role of GHS-R1b remains poorly characterized."},{"rthcId":"RPEP-02120","title":"A parallel semisynthetic approach for structure-activity relationship studies of peptide YY.","authors":"Albertsen, Louise; Østergaard, Søren; Paulsson, Johan F; Norrild, Jens Chr; Strømgaard, Kristian","year":2013,"journal":"ChemMedChem, 8(9), 1505-13, 1422","doi":"10.1002/cmdc.201300290","pmid":"23907926","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Using an intein-based expression system combined with parallel solid-phase synthesis, researchers generated an array of C-terminally modified PYY(3-36) analogues with substitutions at positions Arg33, Gln34, Arg35, and Tyr36.\n\nKey findings from functional Y2 receptor assays:\n- Substitutions at Tyr36 were generally better tolerated than modifications at Arg33, Gln34, or Arg35\n- Arg33, Gln34, and Arg35 were critical for Y2 receptor activation\n- Two analogues showed significantly improved Y2 receptor selectivity compared to native PYY(3-36)\n- These results provide a foundation for designing new PYY-based obesity drug candidates with improved receptor selectivity","whyItMatters":"PYY(3-36) is a natural appetite suppressant that has shown promise in obesity research but hasn't yet become a successful drug partly due to receptor selectivity issues. By systematically engineering the peptide's critical C-terminal region, this work identified improved analogues that could eventually lead to more effective PYY-based obesity medications with fewer side effects.","specificNumbers":"","methodology":"Researchers used an intein-based expression system in E. coli to produce PYY(3-29) as a C-terminal peptide α-thioester. Heptapeptides with an N-terminal cysteine and C-terminal modifications were synthesized in parallel using 96-well plate solid-phase synthesis. The fragments were joined by native chemical ligation, followed by desulfurization and solid-phase extraction. The resulting analogues were tested in a functional Y2 receptor assay.","limitations":"This was an in vitro study focused on receptor binding and selectivity, with no animal or human testing. Improved Y2 selectivity in a receptor assay does not guarantee improved efficacy or safety in vivo. Pharmacokinetic properties like metabolic stability and bioavailability of the analogues were not assessed. The semi-synthetic approach, while efficient, is limited to modifications at the C-terminal end."},{"rthcId":"RPEP-02121","title":"CKD273, a new proteomics classifier assessing CKD and its prognosis.","authors":"Argilés, Ángel; Siwy, Justyna; Duranton, Flore; Gayrard, Nathalie; Dakna, Mohammed; Lundin, Ulrika; Osaba, Lourdes; Delles, Christian; Mourad, Georges; Weinberger, Klaus M; Mischak, Harald","year":2013,"journal":"PloS one, 8(5), e62837","doi":"10.1371/journal.pone.0062837","pmid":"23690958","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02122","title":"Development of a selective peptide macrocycle inhibitor of coagulation factor XII toward the generation of a safe antithrombotic therapy.","authors":"Baeriswyl, Vanessa; Calzavarini, Sara; Gerschheimer, Christiane; Diderich, Philippe; Angelillo-Scherrer, Anne; Heinis, Christian","year":2013,"journal":"Journal of medicinal chemistry, 56(9), 3742-6","doi":"10.1021/jm400236j","pmid":"23586812","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02123","title":"Polycyclic peptide therapeutics.","authors":"Baeriswyl, Vanessa; Heinis, Christian","year":2013,"journal":"ChemMedChem, 8(3), 377-84","doi":"10.1002/cmdc.201200513","pmid":"23355488","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02124","title":"Ghrelin knockout mice show decreased voluntary alcohol consumption and reduced ethanol-induced conditioned place preference.","authors":"Bahi, Amine; Tolle, Virginie; Fehrentz, Jean-Alain; Brunel, Luc; Martinez, Jean; Tomasetto, Catherine-Laure; Karam, Sherif M","year":2013,"journal":"Peptides, 43, 48-55","doi":"10.1016/j.peptides.2013.02.008","pmid":"23428971","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02125","title":"Self-assembling multidomain peptide fibers with aromatic cores.","authors":"Bakota, Erica L; Sensoy, Ozge; Ozgur, Beytullah; Sayar, Mehmet; Hartgerink, Jeffrey D","year":2013,"journal":"Biomacromolecules, 14(5), 1370-8","doi":"10.1021/bm4000019","pmid":"23480446","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02126","title":"Chronic intranasal oxytocin causes long-term impairments in partner preference formation in male prairie voles.","authors":"Bales, Karen L; Perkeybile, Allison M; Conley, Olivia G; Lee, Meredith H; Guoynes, Caleigh D; Downing, Griffin M; Yun, Catherine R; Solomon, Marjorie; Jacob, Suma; Mendoza, Sally P","year":2013,"journal":"Biological psychiatry, 74(3), 180-8","doi":"10.1016/j.biopsych.2012.08.025","pmid":"23079235","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02127","title":"Mortal hyperkalemia disturbances in rats are NO-system related. The life saving effect of pentadecapeptide BPC 157.","authors":"Barisic, Ivan; Balenovic, Diana; Klicek, Robert; Radic, Bozo; Nikitovic, Bojana; Drmic, Domagoj; Udovicic, Mario; Strinic, Dean; Bardak, Darija; Berkopic, Lidija; Djuzel, Viktor; Sever, Marko; Cvjetko, Ivan; Romic, Zeljko; Sindic, Aleksandra; Bencic, Martina Lovric; Seiwerth, Sven; Sikiric, Predrag","year":2013,"journal":"Regulatory peptides, 181, 50-66","doi":"10.1016/j.regpep.2012.12.007","pmid":"23327997","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02128","title":"Effect of dairy proteins on appetite, energy expenditure, body weight, and composition: a review of the evidence from controlled clinical trials.","authors":"Bendtsen, Line Q; Lorenzen, Janne K; Bendsen, Nathalie T; Rasmussen, Charlotte; Astrup, Arne","year":2013,"journal":"Advances in nutrition (Bethesda, Md.), 4(4), 418-38","doi":"10.3945/an.113.003723","pmid":"23858091","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02129","title":"Other than growth hormone neuroendocrine actions of ghrelin.","authors":"Benso, Andrea; Calvi, Elisa; Gramaglia, Elena; Olivetti, Ilaria; Tomelini, Michela; Ghigo, Ezio; Broglio, Fabio","year":2013,"journal":"Endocrine development, 25, 59-68","doi":"10.1159/000346054","pmid":"23652392","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Ghrelin influences multiple neuroendocrine axes: (1) It stimulates the HPA axis (stress response) independently of the pituitary, acting through the hypothalamus via CRH, AVP, and neuropeptide Y. (2) In ACTH-secreting tumors (Cushing's disease), pathological ghrelin receptor expression causes especially high ACTH and cortisol responses. (3) Ghrelin stimulates prolactin release from somatomammotroph cells. (4) Effects on thyroid axis regulation remain controversial. (5) Ghrelin inhibits FSH and especially LH secretion, likely through hypothalamic inhibition of GnRH.","whyItMatters":"Understanding ghrelin's broad hormonal effects is crucial as drugs targeting the ghrelin system are developed for obesity, cachexia, and growth hormone disorders. Unintended effects on stress hormones, fertility, and other systems could become side effects. The Cushing's disease connection also has diagnostic implications — ghrelin stimulation tests could help identify ACTH-secreting tumors.","specificNumbers":"","methodology":"This is a narrative review chapter summarizing published human and animal studies on ghrelin's neuroendocrine actions beyond growth hormone release, covering the HPA axis, prolactin, thyroid, and gonadal systems.","limitations":"This is a 2013 review chapter, so it does not include the most recent decade of ghrelin research. The thyroid effects remain controversial even within the review. Much of the evidence for specific mechanisms comes from animal studies that may not fully translate to humans. Quantitative data on effect sizes for each hormonal axis are not provided in the abstract."},{"rthcId":"RPEP-02130","title":"Elastin-derived peptides are new regulators of insulin resistance development in mice.","authors":"Blaise, Sébastien; Romier, Béatrice; Kawecki, Charlotte; Ghirardi, Maxime; Rabenoelina, Fanja; Baud, Stéphanie; Duca, Laurent; Maurice, Pascal; Heinz, Andrea; Schmelzer, Christian E H; Tarpin, Michel; Martiny, Laurent; Garbar, Christian; Dauchez, Manuel; Debelle, Laurent; Durlach, Vincent","year":2013,"journal":"Diabetes, 62(11), 3807-16","doi":"10.2337/db13-0508","pmid":"23919962","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Elastin-derived peptides (EDPs) — fragments released when the structural protein elastin breaks down during aging — were found to directly cause insulin resistance in mice. When injected intravenously (either as a single dose or repeatedly), EDPs triggered hyperglycemia and reduced glucose uptake in skeletal muscle, liver, and adipose tissue. The mechanism involves EDPs activating the elastin receptor complex, whose neuraminidase-1 subunit then interacts with the insulin receptor. This interaction strips sialic acid residues from the insulin receptor's beta-chain, impairing its signaling cascade. This is the first study to show that elastin degradation products — which naturally accumulate as we age — can directly interfere with insulin signaling and promote insulin resistance.","whyItMatters":"This study offers a novel explanation for why insulin resistance tends to develop with aging. Rather than focusing on the usual suspects like diet, obesity, or inflammation, it points to a structural change: the gradual breakdown of elastin in blood vessel walls and connective tissue releases peptide fragments that actively disrupt insulin signaling. If confirmed in humans, this could open entirely new therapeutic targets for age-related type 2 diabetes.","specificNumbers":"","methodology":"The researchers used a combination of in vivo mouse experiments, in vitro cell studies, and computer modeling. C57BL/6 mice on a standard diet received either acute or chronic intravenous injections of elastin-derived peptides. Blood glucose levels and tissue-specific glucose uptake were measured. The molecular mechanism was investigated by examining the interaction between the elastin receptor complex (specifically its neuraminidase-1 subunit) and the insulin receptor, including analysis of sialic acid levels on the insulin receptor's beta-chain.","limitations":"This was an animal study using C57BL/6 mice, so the findings may not directly translate to humans. The EDPs were delivered intravenously rather than accumulating naturally, which may not perfectly replicate the aging process. The study did not measure the actual concentrations of EDPs that accumulate in aging tissues in vivo, making it difficult to know whether physiologically relevant levels would produce the same effects."},{"rthcId":"RPEP-02131","title":"Endogenous opiates and behavior: 2012.","authors":"Bodnar, Richard J","year":2013,"journal":"Peptides, 50, 55-95","doi":"10.1016/j.peptides.2013.10.001","pmid":"24126281","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02132","title":"Role of tachykinin 1 and 4 gene-derived neuropeptides and the neurokinin 1 receptor in adjuvant-induced chronic arthritis of the mouse.","authors":"Borbély, Eva; Hajna, Zsófia; Sándor, Katalin; Kereskai, László; Tóth, István; Pintér, Erika; Nagy, Péter; Szolcsányi, János; Quinn, John; Zimmer, Andreas; Stewart, James; Paige, Christopher; Berger, Alexandra; Helyes, Zsuzsanna","year":2013,"journal":"PloS one, 8(4), e61684","doi":"10.1371/journal.pone.0061684","pmid":"23626716","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02133","title":"Identification of GPR39 receptor and ghrelin receptor in thyroid tissues in paediatric patients with immune and non-immune thyroid diseases.","authors":"Bossowski, Artur; Czarnocka, Barbara; Harasymczuk, Jerzy; Moniuszko, Anna; Bardadin, Krzysztof; Lyczkowska, Anna; Hanusek, Karolina; Bossowska, Anna","year":2013,"journal":"Hormone research in paediatrics, 79, 130-6","doi":"10.1159/000347218","pmid":"23485550","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02134","title":"Role of Pituitary Adenylate-Cyclase Activating Polypeptide and Tac1 gene derived tachykinins in sensory, motor and vascular functions under normal and neuropathic conditions.","authors":"Botz, Bálint; Imreh, András; Sándor, Katalin; Elekes, Krisztián; Szolcsányi, János; Reglődi, Dóra; Quinn, John P; Stewart, James; Zimmer, Andreas; Hashimoto, Hitoshi; Helyes, Zsuzsanna","year":2013,"journal":"Peptides, 43, 105-12","doi":"10.1016/j.peptides.2013.03.003","pmid":"23499760","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Using partial sciatic nerve ligation in gene-deficient mice:\n\n- PACAP(-/-) mice: Did NOT develop mechanical hyperalgesia (30-40% in wildtype), identifying PACAP as crucial for neuropathic pain\n- Tac1(-/-) mice (lacking SP/NKA): Developed hyperalgesia normally — tachykinins are NOT required for neuropathic pain\n- Tacr1(-/-) mice (lacking NK1 receptor): Also developed hyperalgesia normally\n- Motor coordination: Impaired in both PACAP(-/-) and Tac1(-/-) mice, unaffected in Tacr1(-/-)\n- Basal skin blood flow: Reduced in Tac1(-/-) and Tacr1(-/-), normal in PACAP(-/-)\n- Neurogenic vasodilation (mustard oil): Significantly reduced in PACAP(-/-), normal in Tac1(-/-) and Tacr1(-/-)\n\nConclusion: PACAP and tachykinins have distinct, non-overlapping roles in pain, vascular regulation, and motor function.","whyItMatters":"Neuropathic pain affects millions and is notoriously difficult to treat. Identifying PACAP as a crucial mediator — when substance P (long thought to be the key pain peptide) turned out not to be required — fundamentally shifts the drug target landscape. Developing PACAP antagonists could open new treatment approaches for chronic nerve pain.","specificNumbers":"","methodology":"Gene-deficient (knockout) mice for PACAP, Tac1 (substance P/NKA), and Tacr1 (NK1 receptor) underwent partial sciatic nerve ligation to model neuropathic pain. Mechanical pain threshold was measured with dynamic plantar aesthesiometry, motor coordination with Rota-Rod, and skin blood flow with laser Doppler imaging. Neurogenic vasodilation was tested with mustard oil stimulation.","limitations":"Mouse models of neuropathic pain may not fully recapitulate human conditions. Compensatory mechanisms in knockout mice could mask or exaggerate the roles of individual peptides. Only one model of neuropathic pain (partial sciatic nerve ligation) was tested. The downstream targets of PACAP mediating neuropathic pain were not identified in this study."},{"rthcId":"RPEP-02135","title":"Sequential release of milk protein-derived bioactive peptides in the jejunum in healthy humans.","authors":"Boutrou, Rachel; Gaudichon, Claire; Dupont, Didier; Jardin, Julien; Airinei, Gheorghe; Marsset-Baglieri, Agnès; Benamouzig, Robert; Tomé, Daniel; Leonil, Joëlle","year":2013,"journal":"The American journal of clinical nutrition, 97(6), 1314-23","doi":"10.3945/ajcn.112.055202","pmid":"23576048","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"After ingestion of 30 g of isotope-labeled casein, 356 peptides were detected and sequenced in the jejunum over 6 hours, compared to 146 peptides from whey protein. β-casein was the dominant precursor of bioactive peptides.\n\nCritically, β-casomorphins (β-casein fragments 57-66, with opioid activity) and β-casein 108-113 (with antihypertensive activity) were released at concentrations sufficient to elicit their known biological actions. Casein released medium-sized peptides (750-1050 kDa) continuously over 6 hours, while whey protein released larger peptides (1050-1800 kDa) primarily in the first 3 hours, reflecting their different digestive kinetics.","whyItMatters":"While bioactive peptides from milk have been studied extensively in vitro, proving they actually form in sufficient quantities during human digestion has been a major gap. This study provides direct evidence from the human gut that dairy digestion generates opioid and blood pressure-lowering peptides at biologically meaningful levels, validating the concept that food-derived peptides can have physiological effects beyond basic nutrition.","specificNumbers":"","methodology":"Healthy human volunteers (n=13: 7 casein, 6 whey protein) were equipped with double-lumen nasogastric tubes positioned in the proximal jejunum. After ingesting 30 g of nitrogen-15-labeled casein or whey protein, intestinal samples were collected over 6 hours. Nitrogen flow rates were measured, and peptides were identified and sequenced using liquid chromatography-tandem mass spectrometry. The registered clinical trial (NCT00862329) allowed direct characterization of peptides at the site of absorption.","limitations":"Small sample size (7 casein, 6 whey protein subjects). The study measured peptide presence in the jejunum but did not directly measure downstream physiological effects (opioid activity, blood pressure changes) in the participants. Nasogastric tube placement may alter normal digestive physiology. The labeled proteins were given in isolation, not as part of a complete meal, which could affect digestive kinetics. Whether these peptides survive further digestion and reach systemic circulation was not assessed."},{"rthcId":"RPEP-02136","title":"Vasopressin modulates neural responses during human reactive aggression.","authors":"Brunnlieb, Claudia; Münte, Thomas F; Krämer, Ulrike; Tempelmann, Claus; Heldmann, Marcus","year":2013,"journal":"Social neuroscience, 8(2), 148-64","doi":"10.1080/17470919.2013.763654","pmid":"23360100","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02137","title":"Preptin analogues: chemical synthesis, secondary structure and biological studies.","authors":"Buchanan, Christina M; Peng, Zhenzhen; Cefre, Aiko; Sarojini, Vijayalekshmi","year":2013,"journal":"Chemical biology & drug design, 82(4), 429-37","doi":"10.1111/cbdd.12168","pmid":"23745966","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02138","title":"Proteolytically activated anti-bacterial hydrogel microspheres.","authors":"Buhrman, Jason S; Cook, Laura C; Rayahin, Jamie E; Federle, Michael J; Gemeinhart, Richard A","year":2013,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 171(3), 288-95","doi":"10.1016/j.jconrel.2013.06.023","pmid":"23816641","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02139","title":"Enkephalin and dynorphin mRNA expression are associated with resilience or vulnerability to chronic social defeat stress.","authors":"Bérubé, Patrick; Laforest, Sylvie; Bhatnagar, Seema; Drolet, Guy","year":2013,"journal":"Physiology & behavior, 122, 237-45","doi":"10.1016/j.physbeh.2013.04.009","pmid":"23665402","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Enkephalin (ENK) mRNA expression was significantly lower in the basolateral amygdala of stress-vulnerable rats compared to both control and resilient rats, with no difference between resilient and control groups.\n\nDynorphin (DYN) mRNA was increased in the dorsal and medial shell of the nucleus accumbens only in vulnerable rats compared to controls. In contrast, DYN was increased in the central striatum (caudal part) specifically in resilient rats. Resilience was defined as average defeat latency >350 seconds over seven days of social defeat, while vulnerability was defined as <350 seconds.","whyItMatters":"Understanding why some individuals are resilient to chronic stress while others develop anxiety, depression, or PTSD-like symptoms is a major challenge in mental health. This study implicates the brain's own opioid peptide systems — which are druggable targets — as key players in stress adaptation, potentially opening new therapeutic avenues for stress-related psychiatric disorders.","specificNumbers":"","methodology":"Sprague-Dawley rats were subjected to a resident-intruder social defeat paradigm for 7 consecutive days. Based on average latency to assume a subordinate posture, rats were classified as vulnerable (<350 seconds) or resilient (>350 seconds). Rats were euthanized 24 hours after the final stress session. ENK and DYN mRNA expression were measured in specific brain regions including the amygdala, nucleus accumbens, and striatum using in situ hybridization or similar molecular techniques.","limitations":"This is a preclinical rat study, and brain region-specific opioid peptide changes may not directly map onto human stress responses. The sample was male-only, so sex differences were not examined. The classification of resilience vs. vulnerability used a single behavioral measure (defeat latency). The study measured mRNA expression, not actual peptide levels, which may not fully reflect functional protein activity."},{"rthcId":"RPEP-02140","title":"Pharmacokinetic study of Growth Hormone-Releasing Peptide 6 (GHRP-6) in nine male healthy volunteers.","authors":"Cabrales, Ania; Gil, Jeovanis; Fernández, Eduardo; Valenzuela, Carmen; Hernández, Francisco; García, Idrián; Hernández, Ariadna; Besada, Vladimir; Reyes, Osvaldo; Padrón, Gabriel; Berlanga, Jorge; Guillén, Gerardo; González, Luis Javier","year":2013,"journal":"European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 48(1-2), 40-6","doi":"10.1016/j.ejps.2012.10.006","pmid":"23099431","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02141","title":"Cardioprotective effect of ghrelin in cardiopulmonary bypass involves a reduction in inflammatory response.","authors":"Cao, Yukun; Tang, Jun; Yang, Ting; Ma, Heng; Yi, Dinghua; Gu, Chunhu; Yu, Shiqiang","year":2013,"journal":"PloS one, 8(1), e55021","doi":"10.1371/journal.pone.0055021","pmid":"23359315","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Ghrelin provided comprehensive cardioprotection during cardiopulmonary bypass in rats:\n\n• Reduced inflammatory markers: TNF-α, IL-6, and myocardial myeloperoxidase activity were all decreased\n• Reduced apoptosis (programmed cell death) in heart muscle cells\n• Decreased oxidative stress in cardiac tissue\n• Lowered levels of myocardial injury markers\n• Significantly improved cardiac function after CPB\n• In cultured cardiomyocytes, ghrelin increased cell viability and decreased apoptosis during simulated CPB\n• Blocking the ghrelin receptor (with [D-Lys3]-GHRP-6) or the PI3K/Akt pathway (with wortmannin) eliminated all protective effects, confirming the mechanism involves GHSR-1a receptor activation and downstream Akt signaling","whyItMatters":"Millions of patients undergo cardiopulmonary bypass annually for heart surgeries, and the procedure itself causes significant heart damage through inflammation and ischemia-reperfusion injury. There is an unmet clinical need for agents that protect the heart during CPB. This study suggests ghrelin could be such an agent, reducing multiple pathways of injury simultaneously through a well-defined mechanism.","specificNumbers":"","methodology":"Adult male Sprague-Dawley rats were subjected to cardiopulmonary bypass and randomized into four groups of 8: vehicle, ghrelin, ghrelin plus GHSR-1a inhibitor, and ghrelin plus PI3K inhibitor. Researchers measured inflammatory markers (TNF-α, IL-6, myeloperoxidase), oxidative stress, apoptosis, cardiac injury biomarkers, and cardiac function. Complementary in vitro experiments used cultured cardiomyocytes subjected to simulated CPB conditions to confirm findings and test mechanisms.","limitations":"This was an animal study in rats, and CPB in rats differs from human cardiac surgery in duration, complexity, and scale. The study measured acute effects only — long-term cardioprotection was not assessed. Ghrelin dosing in rats may not translate directly to human dosing. The study used only male rats, limiting generalizability. No comparison was made with existing cardioprotective strategies used during human CPB."},{"rthcId":"RPEP-02142","title":"Identification of bioactive peptides in hypoallergenic infant milk formulas by CE-TOF-MS assisted by semiempirical model of electromigration behavior.","authors":"Català-Clariana, Sergio; Benavente, Fernando; Giménez, Estela; Barbosa, José; Sanz-Nebot, Victoria","year":2013,"journal":"Electrophoresis, 34(13), 1886-94","doi":"10.1002/elps.201200547","pmid":"23564639","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02143","title":"Arresting inflammation: contributions of plasma membrane and endosomal signalling to neuropeptide-driven inflammatory disease.","authors":"Cattaruzza, Fiore; Poole, Daniel P; Bunnett, Nigel W","year":2013,"journal":"Biochemical Society transactions, 41(1), 137-43","doi":"10.1042/BST20120343","pmid":"23356273","tags":[],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Neuropeptides like substance P drive inflammation through two distinct signaling waves: one at the cell surface and a second from inside the cell after the receptor is internalized into endosomes. Enzymes at each location control the intensity of these signals.\n\nDeleting neprilysin (a surface enzyme that breaks down substance P) worsens inflammation because more pro-inflammatory peptide accumulates. Conversely, blocking ECE-1 (an enzyme inside endosomes) actually reduces inflammation by preventing receptors from recycling back to the surface for another round of signaling. β-arrestin proteins, which shuttle receptors into endosomes, also play a direct role in inflammatory cell migration and pro-inflammatory signaling.","whyItMatters":"Most anti-inflammatory drugs target receptors at the cell surface with a broad, blunt approach. This review reveals that neuropeptide-driven inflammation has two distinct phases — surface signaling and endosomal signaling — that can be targeted independently. Blocking the endosomal recycling pathway (via ECE-1 inhibition) could offer a more selective anti-inflammatory strategy that dampens sustained inflammation without shutting down all receptor activity.","specificNumbers":"Not applicable (narrative review)","methodology":"Narrative review synthesizing research on GPCR signaling mechanisms for neuropeptides, integrating findings from cell-based studies and genetic knockout models to map how plasma membrane and endosomal signaling contribute to inflammation.","limitations":"Most of the mechanisms described were studied in model cell systems rather than in vivo human disease. The relative contribution of plasma membrane versus endosomal signaling in complex inflammatory diseases remains unclear. No clinical data on targeting these pathways therapeutically."},{"rthcId":"RPEP-02144","title":"Identification of Bioactive Peptides from Cereal Storage Proteins and Their Potential Role in Prevention of Chronic Diseases.","authors":"Cavazos, Ariel; Gonzalez de Mejia, Elvira","year":2013,"journal":"Comprehensive reviews in food science and food safety, 12(4), 364-380","doi":"10.1111/1541-4337.12017","pmid":"33412684","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"All four cereal grains analyzed (wheat, oat, barley, and rice) contained high frequencies of ACE-inhibitor peptide sequences (occurrence frequencies A = 0.239 to 0.511), along with DPP-IV inhibitor, antithrombotic, antioxidant, hypotensive, and opioid peptide sequences. Wheat and rice proteins specifically contained anticancer sequences. Wheat and barley showed the greatest diversity and abundance of potential biological activity among the cereal proteins evaluated.","whyItMatters":"Most bioactive peptide research has focused on dairy and legume proteins. This review demonstrates that cereal grains — the most widely consumed food group globally — also harbor extensive bioactive peptide sequences. This provides a molecular basis for the well-documented health benefits of whole grain consumption and suggests cereal-derived peptides could be developed into functional food ingredients.","specificNumbers":"4 cereal grains analyzed · ACE-inhibitor frequency A = 0.239–0.511 · Wheat + rice contain anticancer sequences · Wheat + barley = greatest peptide diversity","methodology":"The researchers used the BIOPEP database to identify potential bioactive peptide sequences within the storage proteins of wheat, oat, barley, and rice. They calculated occurrence frequencies for various bioactive peptide types (ACE-inhibitory, DPP-IV inhibitory, antithrombotic, antioxidant, hypotensive, opioid, anticancer). Published research on each grain's protein effects in chronic disease prevention was also compiled and reviewed.","limitations":"This is a bioinformatics-based review, not an experimental study. Identifying peptide sequences in a database does not prove they are actually released during digestion, survive absorption, or reach target tissues in active form. The occurrence frequencies represent theoretical potential, not measured biological activity. No human clinical data is presented."},{"rthcId":"RPEP-02145","title":"Pentadecapeptide BPC 157 and the esophagocutaneous fistula healing therapy.","authors":"Cesarec, Vedran; Becejac, Tomislav; Misic, Marija; Djakovic, Zeljko; Olujic, Danijela; Drmic, Domagoj; Brcic, Luka; Rokotov, Dinko Stancic; Seiwerth, Sven; Sikiric, Predrag","year":2013,"journal":"European journal of pharmacology, 701(1-3), 203-12","doi":"10.1016/j.ejphar.2012.11.055","pmid":"23220707","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02146","title":"Stapled α-helical peptide drug development: a potent dual inhibitor of MDM2 and MDMX for p53-dependent cancer therapy.","authors":"Chang, Yong S; Graves, Bradford; Guerlavais, Vincent; Tovar, Christian; Packman, Kathryn; To, Kwong-Him; Olson, Karen A; Kesavan, Kamala; Gangurde, Pranoti; Mukherjee, Aditi; Baker, Theresa; Darlak, Krzysztof; Elkin, Carl; Filipovic, Zoran; Qureshi, Farooq Z; Cai, Hongliang; Berry, Pamela; Feyfant, Eric; Shi, Xiangguo E; Horstick, James; Annis, D Allen; Manning, Anthony M; Fotouhi, Nader; Nash, Huw; Vassilev, Lyubomir T; Sawyer, Tomi K","year":2013,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 110(36), E3445-54","doi":"10.1073/pnas.1303002110","pmid":"23946421","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02147","title":"Cerebrolysin enhances cognitive recovery of mild traumatic brain injury patients: double-blind, placebo-controlled, randomized study.","authors":"Chen, Chun-Chung; Wei, Sung-Tai; Tsaia, Shiu-Chiu; Chen, Xian-Xiu; Cho, Der-Yang","year":2013,"journal":"British journal of neurosurgery, 27(6), 803-7","doi":"10.3109/02688697.2013.793287","pmid":"23656173","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02148","title":"Cerebrolysin for vascular dementia.","authors":"Chen, Ning; Yang, Mi; Guo, Jian; Zhou, Muke; Zhu, Cairong; He, Li","year":2013,"journal":"The Cochrane database of systematic reviews, CD008900","doi":"10.1002/14651858.CD008900.pub2","pmid":"23440834","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02149","title":"Liraglutide prevents high glucose level induced insulinoma cells apoptosis by targeting autophagy.","authors":"Chen, Ze-fang; Li, Yan-bo; Han, Jun-yong; Yin, Jia-jing; Wang, Yang; Zhu, Li-bo; Xie, Guang-ying","year":2013,"journal":"Chinese medical journal, 126(5), 937-41","doi":null,"pmid":"23489805","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02150","title":"Neural stem cells encapsulated in a functionalized self-assembling peptide hydrogel for brain tissue engineering.","authors":"Cheng, Tzu-Yun; Chen, Ming-Hong; Chang, Wen-Han; Huang, Ming-Yuan; Wang, Tzu-Wei","year":2013,"journal":"Biomaterials, 34(8), 2005-16","doi":"10.1016/j.biomaterials.2012.11.043","pmid":"23237515","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02151","title":"Antifungal effect and pore-forming action of lactoferricin B like peptide derived from centipede Scolopendra subspinipes mutilans.","authors":"Choi, Hyemin; Hwang, Jae-Sam; Lee, Dong Gun","year":2013,"journal":"Biochimica et biophysica acta, 1828(11), 2745-50","doi":"10.1016/j.bbamem.2013.07.021","pmid":"23896552","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02152","title":"Mesenchymal stem cells expressing vasoactive intestinal peptide ameliorate symptoms in a model of chronic multiple sclerosis.","authors":"Cobo, Marién; Anderson, Per; Benabdellah, Karim; Toscano, Miguel G; Muñoz, Pilar; García-Pérez, Angélica; Gutierrez, Iván; Delgado, Mario; Martin, Francisco","year":2013,"journal":"Cell transplantation, 22(5), 839-54","doi":null,"pmid":"23031550","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"MSCs engineered to express VIP stopped disease progression and reduced symptoms in chronic EAE when given at peak disease. Improvements included decreased anti-MOG T cell responses, reduced CNS inflammation and demyelination, and preserved neuronal integrity. Neither VIP gene therapy alone nor unmodified MSCs were effective at peak disease — only the combination worked.","whyItMatters":"Chronic and progressive MS have no effective treatments. Combining stem cell therapy with VIP peptide delivery addresses both immunoregulation and neuroprotection simultaneously, working even at advanced disease stages where current therapies fail.","specificNumbers":"3.3 kDa VIP peptide; MOG-EAE chronic model; IP administration; effective at peak disease; neither VIP vectors alone nor unmodified MSCs effective alone","methodology":"Allogeneic MSCs were transduced with lentiviral vectors to express processed VIP. Cells were administered intraperitoneally in mice with MOG-induced chronic EAE at peak disease. Outcomes included clinical scoring, peripheral T cell responses, and CNS histopathology (inflammation, demyelination, neuronal integrity). Controls included unmodified MSCs and VIP lentiviral vectors alone.","limitations":"Mouse EAE model may not fully represent human MS pathology. Only intraperitoneal delivery tested. Long-term durability of therapeutic effect not characterized. Lentiviral modification of MSCs raises gene therapy safety considerations. Small animal numbers typical of EAE studies."},{"rthcId":"RPEP-02153","title":"Evaluation of a possible direct effect by casein phosphopeptides on paracellular and vitamin D controlled transcellular calcium transport mechanisms in intestinal human HT-29 and Caco2 cell lines.","authors":"Colombini, Alessandra; Perego, Silvia; Ardoino, Ilaria; Marasco, Emiliano; Lombardi, Giovanni; Fiorilli, Amelia; Biganzoli, Elia; Tettamanti, Guido; Ferraretto, Anita","year":2013,"journal":"Food & function, 4(8), 1195-203","doi":"10.1039/c3fo60099h","pmid":"23681196","tags":["food-derived-peptides","bioactive-peptides"],"studyType":"basic-research","evidenceStrength":"preliminary","keyFinding":"Casein phosphopeptides (CPPs) — peptides produced when milk protein is digested — increase calcium uptake by intestinal cells, but this study found they do NOT work by modifying the molecular machinery for calcium absorption. Specifically, CPPs did not affect paracellular calcium transport (the pathway between cells), did not alter expression of the TRPV6 calcium channel, and did not change vitamin D receptor (VDR) expression in either HT-29 or Caco2 intestinal cell lines.\n\nThis means CPPs enhance calcium absorption through a different mechanism — likely by keeping calcium in a soluble form that cells can take up more easily, rather than by changing how cells transport calcium. Notably, the study also made a novel discovery: the TRPV6 calcium channel is expressed in HT-29 cells, the first time this had been demonstrated.","whyItMatters":"Understanding exactly how milk-derived peptides enhance calcium absorption matters for developing functional foods and supplements that promote bone health. This study narrows down the mechanism by ruling out direct effects on calcium transport channels, suggesting CPPs work by maintaining calcium solubility in the gut rather than reprogramming intestinal cells. This distinction is important for designing effective calcium supplementation strategies, especially for people at risk of osteoporosis.","specificNumbers":"2 cell lines tested (HT-29, Caco2) · TRPV6 and VDR mRNA expression measured · Vitamin D (1,25(OH)₂D₃) pretreatment · Paracellular transport measured by TEER and Lucifer Yellow · No effect of CPPs on channel expression","methodology":"The researchers used two human intestinal cell lines (HT-29 and Caco2) to test whether casein phosphopeptides directly affect calcium transport machinery. Paracellular transport was measured using transepithelial electrical resistance (TEER) in Caco2 cells and Lucifer Yellow dye flow in HT-29 cells. Transcellular transport machinery was assessed by measuring mRNA expression of the TRPV6 calcium channel and vitamin D receptor (VDR) in cells pre-treated with vitamin D. Both undifferentiated and differentiated cells were tested.","limitations":"This is an in vitro study using cancer-derived cell lines, which may not perfectly replicate normal intestinal cell behavior. The study measured mRNA expression rather than functional protein levels or actual calcium flux through specific channels. Only two cell lines were tested. The mechanism by which CPPs do increase calcium uptake — presumably through solubility effects — was not directly investigated in this study."},{"rthcId":"RPEP-02154","title":"Cyclotide biosynthesis.","authors":"Craik, David J; Malik, Uru","year":2013,"journal":"Current opinion in chemical biology, 17(4), 546-54","doi":"10.1016/j.cbpa.2013.05.033","pmid":"23809361","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02155","title":"The human cathelicidin LL-37 has antiviral activity against respiratory syncytial virus.","authors":"Currie, Silke M; Findlay, Emily Gwyer; McHugh, Brian J; Mackellar, Annie; Man, Tian; Macmillan, Derek; Wang, Hongwei; Fitch, Paul M; Schwarze, Jürgen; Davidson, Donald J","year":2013,"journal":"PloS one, 8(8), e73659","doi":"10.1371/journal.pone.0073659","pmid":"24023689","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02156","title":"Global proteomics and pathway analysis of pressure-overload-induced heart failure and its attenuation by mitochondrial-targeted peptides.","authors":"Dai, Dao-Fu; Hsieh, Edward J; Chen, Tony; Menendez, Lorena G; Basisty, Nathan B; Tsai, Lauren; Beyer, Richard P; Crispin, David A; Shulman, Nicholas J; Szeto, Hazel H; Tian, Rong; MacCoss, Michael J; Rabinovitch, Peter S","year":2013,"journal":"Circulation. Heart failure, 6(5), 1067-76","doi":"10.1161/CIRCHEARTFAILURE.113.000406","pmid":"23935006","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02157","title":"Vasoactive intestinal peptide: a neuropeptide with pleiotropic immune functions.","authors":"Delgado, Mario; Ganea, Doina","year":2013,"journal":"Amino acids, 45(1), 25-39","doi":"10.1007/s00726-011-1184-8","pmid":"22139413","tags":[],"studyType":"review","evidenceStrength":"moderate","keyFinding":"VIP (vasoactive intestinal peptide), a 28-amino-acid neuropeptide, functions far beyond its original discovery as a vasodilator. This review establishes VIP as a major immune regulator produced by both neurons and immune cells. VIP acts on macrophages, dendritic cells, and CD4+ T lymphocytes through specific receptors, modulating inflammatory and autoimmune responses.\n\nThe review covers VIP's involvement in inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis, and other autoimmune conditions, as well as its current clinical applications and future therapeutic potential.","whyItMatters":"VIP represents one of the clearest examples of how neuropeptides bridge the nervous and immune systems. Understanding VIP's immune functions opens therapeutic avenues for autoimmune diseases — conditions where the immune system attacks the body's own tissues. Unlike many immunosuppressants, VIP modulates rather than broadly suppresses immunity, potentially offering more targeted treatments with fewer side effects.","specificNumbers":"28 amino acids · Expressed in CNS and peripheral nervous system · Acts on macrophages, dendritic cells, CD4+ T cells · Multiple receptor subtypes (VPAC1, VPAC2)","methodology":"This is a comprehensive review of published literature on VIP's immune functions, covering VIP production by neurons and immune cells, receptor signaling pathways, effects on specific immune cell types (macrophages, dendritic cells, T lymphocytes), roles in inflammatory and autoimmune disorders, and current and potential therapeutic applications.","limitations":"As a review, this paper synthesizes existing knowledge rather than presenting new data. Much of the evidence for VIP's therapeutic potential comes from animal models of autoimmune disease. The translation of VIP-based therapies to human clinical use has been limited by the peptide's short half-life and delivery challenges."},{"rthcId":"RPEP-02158","title":"Influence of additional resection of the gastric fundus on excessive weight loss in laparoscopic very very long limb Roux-en-Y gastric bypass.","authors":"Delko, T; Köstler, T; Peev, M; Oertli, D; Zingg, U","year":2013,"journal":"Obesity surgery, 23(3), 279-86","doi":"10.1007/s11695-012-0805-y","pmid":"23135881","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02159","title":"Neural plasticity in the gastrointestinal tract: chronic inflammation, neurotrophic signals, and hypersensitivity.","authors":"Demir, Ihsan Ekin; Schäfer, Karl-Herbert; Tieftrunk, Elke; Friess, Helmut; Ceyhan, Güralp O","year":2013,"journal":"Acta neuropathologica, 125(4), 491-509","doi":"10.1007/s00401-013-1099-4","pmid":"23417735","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02160","title":"Crosstalk between diabetes and brain: glucagon-like peptide-1 mimetics as a promising therapy against neurodegeneration.","authors":"Duarte, A I; Candeias, E; Correia, S C; Santos, R X; Carvalho, C; Cardoso, S; Plácido, A; Santos, M S; Oliveira, C R; Moreira, P I","year":2013,"journal":"Biochimica et biophysica acta, 1832(4), 527-41","doi":"10.1016/j.bbadis.2013.01.008","pmid":"23314196","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02161","title":"Decreased intestinal nutrient response in diet-induced obese rats: role of gut peptides and nutrient receptors.","authors":"Duca, F A; Swartz, T D; Sakar, Y; Covasa, M","year":2013,"journal":"International journal of obesity (2005), 37(3), 375-81","doi":"10.1038/ijo.2012.45","pmid":"22546775","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02162","title":"Differentiation of nerve fibers storing CGRP and CGRP receptors in the peripheral trigeminovascular system.","authors":"Eftekhari, Sajedeh; Warfvinge, Karin; Blixt, Frank W; Edvinsson, Lars","year":2013,"journal":"The journal of pain, 14(11), 1289-303","doi":"10.1016/j.jpain.2013.03.010","pmid":"23958278","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02163","title":"Solid phase synthesis of Smac/DIABLO-derived peptides using a 'Safety-Catch' resin: identification of potent XIAP BIR3 antagonists.","authors":"Elsawy, Mohamed A; Martin, Lorraine; Tikhonova, Irina G; Walker, Brian","year":2013,"journal":"Bioorganic & medicinal chemistry, 21(17), 5004-11","doi":"10.1016/j.bmc.2013.06.055","pmid":"23886811","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02164","title":"The six amino acid antimicrobial peptide bLFcin6 penetrates cells and delivers siRNA.","authors":"Fang, Bing; Guo, Hui Y; Zhang, Ming; Jiang, Lu; Ren, Fa Z","year":2013,"journal":"The FEBS journal, 280(4), 1007-17","doi":"10.1111/febs.12093","pmid":"23241223","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02165","title":"Inhibiting roles of berberine in gut movement of rodents are related to activation of the endogenous opioid system.","authors":"Feng, Yajing; Li, Yongyu; Chen, Chunqiu; Lin, Xuhong; Yang, Yuehua; Cai, Haidong; Lv, Zhongwei; Cao, Minghua; Li, Kun; Xu, Jing; Li, Sainan; Jia, Yijun","year":2013,"journal":"Phytotherapy research : PTR, 27(10), 1564-71","doi":"10.1002/ptr.4926","pmid":"23339028","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02166","title":"A comparative protease stability study of synthetic macrocyclic peptides that mimic two endocrine hormones.","authors":"Ferrie, John J; Gruskos, Jessica J; Goldwaser, Ari L; Decker, Megan E; Guarracino, Danielle A","year":2013,"journal":"Bioorganic & medicinal chemistry letters, 23(4), 989-95","doi":"10.1016/j.bmcl.2012.12.041","pmid":"23312470","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02167","title":"Effects of cerebrolysin administration on oxidative stress-induced apoptosis in lymphocytes from CADASIL patients.","authors":"Formichi, Patrizia; Radi, Elena; Battisti, Carla; Di Maio, Giuseppe; Dotti, Maria Teresa; Muresanu, Dafin; Federico, Antonio","year":2013,"journal":"Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 34(4), 553-6","doi":"10.1007/s10072-012-1174-y","pmid":"22878905","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"When cerebrolysin was added to lymphocytes from CADASIL patients cultured under normal conditions, it had no effect on cell death rates. However, when cells were stressed with the pro-apoptotic agent 2-deoxy-D-ribose (dRib), cerebrolysin significantly decreased apoptosis after 48 hours — but only in 5 out of 15 patients (33%).\n\nIn the remaining 10 patients, cerebrolysin showed no protective effect against oxidative stress-induced cell death. The authors concluded that the Notch3 gene mutation in CADASIL probably does not influence cerebrolysin's anti-apoptotic properties, and that the variable response may reflect individual differences in disease biology.","whyItMatters":"CADASIL is a devastating hereditary condition that causes strokes and dementia, and there are currently no disease-modifying treatments. Understanding whether neuroprotective peptide drugs like cerebrolysin could help these patients is an important research question, even if this early in-vitro study found limited effectiveness.","specificNumbers":"","methodology":"The researchers collected peripheral blood lymphocytes from 15 CADASIL patients (ages 34–70). They cultured these cells in the lab and exposed them to 2-deoxy-D-ribose, a sugar that triggers oxidative stress and cell death. Cerebrolysin was then added to see if it could prevent the cells from dying. Cell death was measured using flow cytometry and fluorescence microscopy after 48 hours of culture.","limitations":"This was an in vitro study using blood cells in a lab dish, not brain tissue, so results may not reflect what happens in the brain. The sample size of 15 patients is very small. The study only measured one type of stress (oxidative) and one time point (48 hours). There was no explanation for why 30% of patients responded while 70% did not, beyond speculation about the Notch3 gene."},{"rthcId":"RPEP-02168","title":"Distinct antimicrobial peptide expression determines host species-specific bacterial associations.","authors":"Franzenburg, Sören; Walter, Jonas; Künzel, Sven; Wang, Jun; Baines, John F; Bosch, Thomas C G; Fraune, Sebastian","year":2013,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 110(39), E3730-8","doi":"10.1073/pnas.1304960110","pmid":"24003149","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02169","title":"Growth hormone-releasing hormone effects on brain γ-aminobutyric acid levels in mild cognitive impairment and healthy aging.","authors":"Friedman, Seth D; Baker, Laura D; Borson, Soo; Jensen, J Eric; Barsness, Suzanne M; Craft, Suzanne; Merriam, George R; Otto, Randolph K; Novotny, Edward J; Vitiello, Michael V","year":2013,"journal":"JAMA neurology, 70(7), 883-90","doi":"10.1001/jamaneurol.2013.1425","pmid":"23689947","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02170","title":"An intragastric balloon produces large weight losses in the absence of a change in ghrelin or peptide YY.","authors":"Fuller, N R; Lau, N S; Denyer, G; Caterson, I D","year":2013,"journal":"Clinical obesity, 3(6), 172-9","doi":"10.1111/cob.12030","pmid":"25586733","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Weight loss achieved with an intragastric balloon did not alter fasting levels of peptide YY (PYY) or adiponectin. Ghrelin increased while the balloon was in place (+39.3 pmol/L vs. baseline) but returned to baseline after removal (-34.7 pmol/L). Leptin decreased at 6 months (-11.7 ng/mL) but rebounded to baseline after balloon removal. Critically, no compensatory rise in ghrelin was observed in either group 12 months after initial weight loss, suggesting that this approach may avoid the hormonal rebound that typically drives weight regain after dieting.","whyItMatters":"One of the biggest challenges in weight loss is that the body's appetite hormones shift to promote weight regain. This study suggests that intragastric balloon-assisted weight loss may not trigger the same unfavorable hormonal changes seen with diet alone — particularly the feared compensatory ghrelin surge. Understanding how different weight loss methods affect appetite-regulating peptides is essential for developing strategies that produce lasting results.","specificNumbers":"n=66 · ghrelin +39.3 pmol/L during IGB · ghrelin -34.7 pmol/L after removal · leptin -11.7 ng/mL at 6 months · 12-month follow-up · no compensatory ghrelin rise at 12 months","methodology":"Sixty-six obese adults with metabolic syndrome were randomized into two groups: one received an intragastric balloon for 6 months combined with a 12-month behavioral modification program, while the other received the behavioral program alone. Anthropometric measurements and blood samples were collected every 3 months. Fasting levels of ghrelin, peptide YY, adiponectin, and leptin were measured throughout the study period.","limitations":"The study measured only fasting hormone levels, which may not capture the full postprandial hormonal response. The sample size of 66 participants is moderate. The follow-up period was 12 months, so longer-term hormonal changes remain unknown. The study focused on metabolic syndrome patients, so findings may not generalize to all obese populations."},{"rthcId":"RPEP-02171","title":"Neuroendocrine alterations in the exercising human: implications for energy homeostasis.","authors":"Fuqua, John S; Rogol, Alan D","year":2013,"journal":"Metabolism: clinical and experimental, 62(7), 911-21","doi":"10.1016/j.metabol.2013.01.016","pmid":"23415825","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02172","title":"Identification of lactoferrin peptides generated by digestion with human gastrointestinal enzymes.","authors":"Furlund, C B; Ulleberg, E K; Devold, T G; Flengsrud, R; Jacobsen, M; Sekse, C; Holm, H; Vegarud, G E","year":2013,"journal":"Journal of dairy science, 96(1), 75-88","doi":"10.3168/jds.2012-5946","pmid":"23141828","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Human GI enzyme digestion of bovine lactoferrin generated peptide fragments that differed substantially from those produced by non-human enzymes. Critically, bovine lactoferricin f(17-41) — the most well-characterized antimicrobial fragment — was not detected after either in vitro or in vivo human digestion. Degradation was highly pH-dependent: high gastric enzyme concentration with rapid pH reduction to 2.5 caused complete degradation, while slower pH reduction or higher pH preserved more intact lactoferrin. Proteolytic cutting sites were located on the protein surface, mainly on the non-glycosylated half. A proline-hydrophobic motif was identified that restricted proteolytic processing.","whyItMatters":"Lactoferrin supplements are widely marketed for immune support and antimicrobial benefits, often citing research on lactoferricin and other bioactive fragments. But those fragments were identified using non-human enzymes. This study reveals that human digestion produces fundamentally different peptides, calling into question whether oral lactoferrin supplements actually deliver the specific bioactive peptides that have been studied. This has major implications for supplement efficacy claims.","specificNumbers":"","methodology":"Bovine lactoferrin was digested using actual human gastrointestinal juices in a two-step in vitro model mimicking stomach and duodenal conditions. Gastric pH was varied (slowly or rapidly reduced to 2.5 or 4.0) to simulate different food buffering capacities. Results were compared with in vivo digestion data from 2 human volunteers. Peptides were identified by mass spectrometry and compared to previously reported lactoferrin-derived peptide sequences.","limitations":"Very small in vivo component (only 2 volunteers), limiting the ability to assess individual variation. The in vitro model, while using human GI juices, may still not perfectly replicate the complexity of in vivo digestion. The study focused on bovine lactoferrin; human lactoferrin digestion may differ. Peptide identification may have missed some low-abundance fragments. The functional significance of the newly identified peptides was not tested."},{"rthcId":"RPEP-02173","title":"Biomarkers and diagnostics in heart failure.","authors":"Gaggin, Hanna K; Januzzi, James L","year":2013,"journal":"Biochimica et biophysica acta, 1832(12), 2442-50","doi":"10.1016/j.bbadis.2012.12.014","pmid":"23313577","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02174","title":"Characterization of SNARE proteins in human pituitary adenomas: targeted secretion inhibitors as a new strategy for the treatment of acromegaly?","authors":"Garcia, Edwin A; Trivellin, Giampaolo; Aflorei, Elena D; Powell, Michael; Grieve, Joana; Alusi, Ghassan; Pobereskin, Luis; Shariati, Babak; Cudlip, Simon; Roncaroli, Federico; Mendoza, Nigel; Grossman, Ashley B; Harper, Elaine A; Korbonits, Márta","year":2013,"journal":"The Journal of clinical endocrinology and metabolism, 98(12), E1918-26","doi":"10.1210/jc.2013-2602","pmid":"24152687","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02175","title":"Macimorelin (AEZS-130)-stimulated growth hormone (GH) test: validation of a novel oral stimulation test for the diagnosis of adult GH deficiency.","authors":"Garcia, J M; Swerdloff, R; Wang, C; Kyle, M; Kipnes, M; Biller, B M K; Cook, D; Yuen, K C J; Bonert, V; Dobs, A; Molitch, M E; Merriam, G R","year":2013,"journal":"The Journal of clinical endocrinology and metabolism, 98(6), 2422-9","doi":"10.1210/jc.2013-1157","pmid":"23559086","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Oral macimorelin achieved an area under the ROC curve of 0.96 for diagnosing adult GH deficiency, with 82% sensitivity and 92% specificity at a GH cutoff of 2.7 ng/mL. Peak GH levels differed dramatically between patients and controls: 2.36 ± 5.69 ng/mL in AGHD patients versus 17.71 ± 19.11 ng/mL in healthy controls (P < 0.001).\n\nObesity (BMI > 30 kg/m²), present in 58% of subjects, significantly affected results — peak GH levels were inversely correlated with BMI in controls (r = -0.37, P = 0.01). Using separate cutoffs of 6.8 ng/mL for non-obese and 2.7 ng/mL for obese subjects reduced the overall misclassification rate to 11%. The diagnostic accuracy was comparable to the arginine+GHRH test in the crossover portion of the study.","whyItMatters":"Adult GH deficiency is underdiagnosed partly because existing tests require IV infusions in clinical settings. An oral test that patients simply drink could make diagnosis far more accessible and routine. Macimorelin (later FDA-approved as Macrilen) represented a paradigm shift in endocrine diagnostics — from invasive IV stimulation tests to a simple oral solution.","specificNumbers":"","methodology":"This was a multicenter, open-label study with 50 AGHD patients and 48 matched healthy controls. The first 43 patients and 10 controls received both oral macimorelin and IV arginine+GHRH in a crossover design. When the GHRH analog became unavailable in the US, the remaining 10 patients and 38 controls were tested with macimorelin alone. Peak GH levels were measured and ROC analysis was used to determine optimal diagnostic cutoffs.","limitations":"The study design changed midway when the GHRH analog became unavailable in the US, meaning only a subset of participants completed the full crossover comparison. The open-label design introduces potential bias. The high prevalence of obesity in the study population (58%) complicates interpretation, though the authors addressed this with BMI-specific cutoffs. Sample size, while adequate for a diagnostic validation study, was modest."},{"rthcId":"RPEP-02176","title":"Therapeutic potential of anamorelin, a novel, oral ghrelin mimetic, in patients with cancer-related cachexia: a multicenter, randomized, double-blind, crossover, pilot study.","authors":"Garcia, José M; Friend, John; Allen, Suzan","year":2013,"journal":"Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, 21(1), 129-37","doi":"10.1007/s00520-012-1500-1","pmid":"22699302","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02177","title":"From antimicrobial to anticancer peptides. A review.","authors":"Gaspar, Diana; Veiga, A Salomé; Castanho, Miguel A R B","year":2013,"journal":"Frontiers in microbiology, 4, 294","doi":"10.3389/fmicb.2013.00294","pmid":"24101917","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02178","title":"Potential role of non-insulin adjunct therapy in Type 1 diabetes.","authors":"George, P; McCrimmon, R J","year":2013,"journal":"Diabetic medicine : a journal of the British Diabetic Association, 30(2), 179-88","doi":"10.1111/j.1464-5491.2012.03744.x","pmid":"22804102","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02179","title":"Ectopic acromegaly due to growth hormone releasing hormone.","authors":"Ghazi, Ali A; Amirbaigloo, Alireza; Dezfooli, Azizollah Abbasi; Saadat, Navid; Ghazi, Siavash; Pourafkari, Marina; Tirgari, Farrokh; Dhall, Dheepti; Bannykh, Serguei; Melmed, Shlomo; Cooper, Odelia","year":2013,"journal":"Endocrine, 43(2), 293-302","doi":"10.1007/s12020-012-9790-0","pmid":"22983831","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02180","title":"Friendly strategy to prepare encoded one bead-one compound cyclic peptide library.","authors":"Giudicessi, Silvana L; Gurevich-Messina, Juan M; Martínez-Ceron, María C; Erra-Balsells, Rosa; Albericio, Fernando; Cascone, Osvaldo; Camperi, Silvia A","year":2013,"journal":"ACS combinatorial science, 15(10), 525-9","doi":"10.1021/co400039a","pmid":"23971518","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02181","title":"In vivo regulation of the μ opioid receptor: role of the endogenous opioid agents.","authors":"Gonzalez-Nunez, Veronica; Jimenez González, Ada; Barreto-Valer, Katherine; Rodríguez, Raquel E","year":2013,"journal":"Molecular medicine (Cambridge, Mass.), 19(1), 7-17","doi":"10.2119/molmed.2012.00318","pmid":"23348513","tags":[],"studyType":"animal study","evidenceStrength":"low","keyFinding":"Using zebrafish, researchers demonstrated that endogenous opioid peptides (Met-enkephalin, MEGY, and β-endorphin) regulate the expression of the μ-opioid receptor during brain development, and vice versa — creating a complex feedback loop. Knocking down the μ-opioid receptor gene disrupted normal brain development: dividing cells became disorganized in the optic tectum and mid/hindbrain, and cell death increased significantly in the CNS at 24 hours post-fertilization. Morphine administration also altered expression of the genes that produce endogenous opioid peptides (proenkephalins and proopiomelanocortin), revealing bidirectional regulation between exogenous opioids and the endogenous peptide system.","whyItMatters":"This study reveals that the endogenous opioid peptide system isn't just about pain — it's essential for normal brain development. The finding that removing the μ-opioid receptor causes disorganized cell division and increased cell death in the developing brain has implications for understanding how prenatal opioid exposure might affect brain formation. The complex feedback between opioid peptides and receptors also helps explain why individuals respond differently to opioid medications — baseline variations in this system could modulate drug effects.","specificNumbers":"3 opioid peptides tested (Met-ENK, MEGY, β-END) · Increased apoptosis in CNS at 24h post-fertilization · Disorganized mitotic cells in oprm1-morphant embryos","methodology":"Researchers used zebrafish as a model organism. The zebrafish μ-opioid receptor (dre-oprm1) was characterized for binding affinity to endogenous peptides and morphine. Gene expression was measured during development after treatment with opioid peptides or morphine. Gene knockdown (morpholino oligonucleotides) was used to eliminate oprm1 function. Cell proliferation was assessed by mitotic cell distribution, and cell death was measured using TUNEL staining in the CNS of morphant embryos.","limitations":"Zebrafish, while useful for developmental biology, have significant differences from mammalian brain development. The gene knockdown approach (morpholinos) can have off-target effects. The study examines early developmental effects but doesn't address long-term consequences of opioid system disruption. The relevance to human prenatal opioid exposure is inferred rather than directly demonstrated. The study is from 2013 and some findings may have been extended or modified by subsequent research."},{"rthcId":"RPEP-02182","title":"Oxytocin enhances brain function in children with autism.","authors":"Gordon, Ilanit; Vander Wyk, Brent C; Bennett, Randi H; Cordeaux, Cara; Lucas, Molly V; Eilbott, Jeffrey A; Zagoory-Sharon, Orna; Leckman, James F; Feldman, Ruth; Pelphrey, Kevin A","year":2013,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 110(52), 20953-8","doi":"10.1073/pnas.1312857110","pmid":"24297883","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02183","title":"Recommendations for the standardisation of oxytocin nasal administration and guidelines for its reporting in human research.","authors":"Guastella, Adam J; Hickie, Ian B; McGuinness, Margaret M; Otis, Melissa; Woods, Elizabeth A; Disinger, Hannah M; Chan, Hak-Kim; Chen, Timothy F; Banati, Richard B","year":2013,"journal":"Psychoneuroendocrinology, 38(5), 612-25","doi":"10.1016/j.psyneuen.2012.11.019","pmid":"23265311","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02184","title":"Genetics of the ghrelin system.","authors":"Gueorguiev, Maria; Korbonits, Márta","year":2013,"journal":"Endocrine development, 25, 25-40","doi":"10.1159/000348665","pmid":"23652389","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02185","title":"In silico approach for predicting toxicity of peptides and proteins.","authors":"Gupta, Sudheer; Kapoor, Pallavi; Chaudhary, Kumardeep; Gautam, Ankur; Kumar, Rahul; Raghava, Gajendra P S","year":2013,"journal":"PloS one, 8(9), e73957","doi":"10.1371/journal.pone.0073957","pmid":"24058508","tags":["drug-development"],"studyType":"computational","evidenceStrength":"moderate","keyFinding":"Researchers built a machine learning tool called ToxinPred that predicts whether a peptide is toxic or non-toxic with 94.50% accuracy and a Matthews correlation coefficient (MCC) of 0.88. The model uses dipeptide composition — the frequency of all possible two-amino-acid combinations — as its primary feature set.\n\nWhen tested on independent datasets (peptides not used during training), the model still achieved roughly 90% accuracy, indicating the results aren't just an artifact of overfitting. The team also found that certain amino acids — cysteine, histidine, asparagine, and proline — appear more frequently and at preferred positions in toxic peptides compared to non-toxic ones.\n\nBeyond simple yes/no toxicity prediction, the tool can identify the minimum mutations needed to increase or decrease a peptide's toxicity and pinpoint toxic regions within larger proteins.","whyItMatters":"One of the biggest obstacles in developing peptide-based drugs is toxicity — a promising therapeutic peptide can fail if it turns out to be harmful. Screening every candidate peptide in the lab is slow and expensive. ToxinPred offers a computational shortcut: researchers can screen peptide sequences for potential toxicity before investing in wet-lab experiments. This kind of filtering could speed up drug discovery pipelines and reduce the number of candidates that fail late in development due to safety concerns.","specificNumbers":"94.50% accuracy · MCC 0.88 · ~90% accuracy on independent validation · peptides ≤35 residues · toxic peptides enriched in Cys, His, Asn, Pro","methodology":"The researchers collected known toxic peptides (35 amino acids or fewer) from established databases, and gathered non-toxic peptides from SwissProt and TrEMBL protein databases. They analyzed amino acid composition and positional preferences in toxic vs. non-toxic peptides, then built prediction models using machine learning and quantitative matrices based on dipeptide composition. They also extracted sequence motifs from toxic peptides and combined this information into a hybrid model. The best model was validated on independent datasets to check for overfitting.","limitations":"The model was trained on peptides of 35 residues or fewer, so its accuracy on longer peptides or full proteins is uncertain. The non-toxic training set was drawn from general protein databases rather than confirmed non-toxic therapeutic peptides, which could introduce noise. The ~90% validation accuracy, while strong, means roughly 1 in 10 predictions may be wrong — so lab confirmation is still essential. The study also doesn't account for dose-dependent toxicity or toxicity that emerges only in living organisms."},{"rthcId":"RPEP-02186","title":"Enterococcus faecalis strains from food, environmental, and clinical origin produce ACE-inhibitory peptides and other bioactive peptides during growth in bovine skim milk.","authors":"Gútiez, Loreto; Gómez-Sala, Beatriz; Recio, Isidra; del Campo, Rosa; Cintas, Luis M; Herranz, Carmen; Hernández, Pablo E","year":2013,"journal":"International journal of food microbiology, 166(1), 93-101","doi":"10.1016/j.ijfoodmicro.2013.06.019","pmid":"23845432","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02187","title":"Comparing bacterial membrane interactions and antimicrobial activity of porcine lactoferricin-derived peptides.","authors":"Han, F F; Gao, Y H; Luan, C; Xie, Y G; Liu, Y F; Wang, Y Z","year":2013,"journal":"Journal of dairy science, 96(6), 3471-87","doi":"10.3168/jds.2012-6104","pmid":"23567049","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02188","title":"Oxime side-chain cross-links in an α-helical coiled-coil protein: structure, thermodynamics, and folding-templated synthesis of bicyclic species.","authors":"Haney, Conor M; Horne, W Seth","year":2013,"journal":"Chemistry (Weinheim an der Bergstrasse, Germany), 19(34), 11342-51","doi":"10.1002/chem.201300506","pmid":"23843311","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02189","title":"Omega-conotoxins as experimental tools and therapeutics in pain management.","authors":"Hannon, Heidi E; Atchison, William D","year":2013,"journal":"Marine drugs, 11(3), 680-99","doi":"10.3390/md11030680","pmid":"23470283","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02190","title":"Actions of Agonists and Antagonists of the ghrelin/GHS-R Pathway on GH Secretion, Appetite, and cFos Activity.","authors":"Hassouna, Rim; Labarthe, Alexandra; Zizzari, Philippe; Videau, Catherine; Culler, Michael; Epelbaum, Jacques; Tolle, Virginie","year":2013,"journal":"Frontiers in endocrinology, 4, 25","doi":"10.3389/fendo.2013.00025","pmid":"23515849","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02191","title":"Anti-inflammatory effects of exendin-4, a glucagon-like peptide-1 analog, on human peripheral lymphocytes in patients with type 2 diabetes.","authors":"He, Lan; Wong, Chun Kwok; Cheung, Kitty Kt; Yau, Ho Chung; Fu, Anthony; Zhao, Hai-Lu; Leung, Karen Ml; Kong, Alice Ps; Wong, Gary Wk; Chan, Paul Ks; Xu, Gang; Chan, Juliana Cn","year":2013,"journal":"Journal of diabetes investigation, 4(4), 382-92","doi":"10.1111/jdi.12063","pmid":"24843684","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Compared to healthy controls, immune cells (PBMCs) from type 2 diabetes patients showed:\n- Activated MAPK signaling pathways (P38, JNK, and ERK)\n- Elevated superoxide anion (oxidative stress marker)\n- Increased pro-inflammatory cytokines (TNF-α, IL-1β, IL-6)\n- Increased chemokines (CCL5/RANTES and CXCL10/IP-10)\n\nExendin-4 treatment attenuated all of these inflammatory changes, likely through suppression of the p38 MAPK signaling pathway. This demonstrates that GLP-1 receptor agonists have direct anti-inflammatory effects on human immune cells, independent of their metabolic actions.","whyItMatters":"Chronic inflammation drives many of the complications of type 2 diabetes — heart disease, kidney damage, nerve damage, and more. This study provides mechanistic evidence that GLP-1 peptide drugs have direct anti-inflammatory effects on human immune cells, separate from their blood sugar-lowering action. This helps explain the broad organ-protective benefits of GLP-1RAs seen in clinical trials and suggests they may be treating the inflammatory root of diabetic complications, not just the metabolic symptoms.","specificNumbers":"","methodology":"Researchers collected peripheral blood mononuclear cells (PBMCs) from 10 type 2 diabetes patients and 10 sex- and age-matched healthy controls. Cells were cultured with and without exendin-4. MAPK signaling pathway activation in CD4+ T helper lymphocytes and monocytes was analyzed by flow cytometry. Cytokines and chemokines in culture supernatants were measured by cytometric bead array. Superoxide anion levels were assessed by chemiluminescence assay.","limitations":"Small sample size (10 per group) limits statistical power and generalizability. The study was conducted in vitro (cell culture) using isolated immune cells, which may not fully recapitulate the complex in vivo immune environment. Only exendin-4 was tested, so results may not apply equally to all GLP-1RAs. The direct clinical significance of these cell-level changes for patient outcomes was not established. The dose of exendin-4 used in vitro may differ from physiological concentrations."},{"rthcId":"RPEP-02192","title":"Involvement of spinal cord opioid mechanisms in the acute antinociceptive effect of hyperbaric oxygen in mice.","authors":"Heeman, Jacqueline H; Zhang, Yangmiao; Shirachi, Donald Y; Quock, Raymond M","year":2013,"journal":"Brain research, 1540, 42-7","doi":"10.1016/j.brainres.2013.09.050","pmid":"24113418","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02193","title":"Generation of a hematologic malignancy-selective membranolytic peptide from the antimicrobial core (RRWQWR) of bovine lactoferricin.","authors":"Hilchie, Ashley L; Vale, Rachel; Zemlak, Tyler S; Hoskin, David W","year":2013,"journal":"Experimental and molecular pathology, 95(2), 192-8","doi":"10.1016/j.yexmp.2013.07.006","pmid":"23892223","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The six-amino-acid antimicrobial core of lactoferricin (LfcinB6, RRWQWR) was not cytotoxic to cancer cells on its own. Adding a hepta-arginine cell-penetrating sequence via a glycine-glycine linker created MPLfcinB6, which was selectively cytotoxic to human T-leukemia and B-lymphoma cells.\n\nThe killing mechanism involved extensive and irreparable cell membrane damage, confirmed by propidium iodide uptake, dextran uptake, and scanning electron microscopy. While the peptide also triggered ROS production and mitochondrial membrane permeabilization, neither ROS nor caspase activation was essential for cell death — membrane destruction was the primary killing mechanism.","whyItMatters":"Blood cancers like leukemia and lymphoma need new treatment approaches, especially for drug-resistant cases. This peptide kills cancer cells through membrane destruction — a mechanism that's very different from conventional chemotherapy and difficult for cancer cells to develop resistance against. The selectivity for blood cancer cells over normal cells addresses a key challenge in anticancer drug development.","specificNumbers":"","methodology":"Researchers synthesized MPLfcinB6 by conjugating the lactoferricin antimicrobial core (RRWQWR) to a cell-penetrating hepta-arginine sequence via a glycine-glycine linker. Cytotoxicity was assessed against human T-leukemia and B-lymphoma cell lines. Membrane damage was characterized by flow cytometry (propidium iodide and FITC-dextran uptake) and scanning electron microscopy. ROS production, mitochondrial membrane potential, and caspase activation were measured to elucidate the cell death mechanism.","limitations":"This is an in vitro study using cancer cell lines — no animal testing or comparison with primary patient cancer cells was performed. Only two types of blood cancer were tested; selectivity against other cancer types and normal blood cells was not comprehensively characterized. The peptide's stability in blood and potential immunogenicity were not assessed. Whether MPLfcinB6 can reach cancer cells in vivo through systemic administration is unknown."},{"rthcId":"RPEP-02194","title":"Antimicrobial peptides and colitis.","authors":"Ho, Samantha; Pothoulakis, Charalabos; Koon, Hon Wai","year":2013,"journal":"Current pharmaceutical design, 19(1), 40-7","doi":null,"pmid":"22950497","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02195","title":"Structure of class B GPCR corticotropin-releasing factor receptor 1.","authors":"Hollenstein, Kaspar; Kean, James; Bortolato, Andrea; Cheng, Robert K Y; Doré, Andrew S; Jazayeri, Ali; Cooke, Robert M; Weir, Malcolm; Marshall, Fiona H","year":2013,"journal":"Nature, 499(7459), 438-43","doi":"10.1038/nature12357","pmid":"23863939","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The crystal structure of the human CRF1 receptor transmembrane domain was solved in complex with the small-molecule antagonist CP-376395. The structure revealed detailed atomic-level interactions between the receptor and the non-peptide ligand, which binds deep within the receptor's transmembrane helices.\n\nThis was the first transmembrane domain structure determined for any class B GPCR — a receptor family that was previously understood only from structures of its extracellular domain. The structure serves as a template for understanding the entire class B GPCR family, which includes receptors for many important peptide hormones (glucagon, GLP-1, PTH, calcitonin, and others).","whyItMatters":"Class B GPCRs are targets for treating depression, anxiety, diabetes, osteoporosis, and metabolic diseases — collectively affecting hundreds of millions of people. Before this structure, drug designers working on these receptors were essentially working blind in the membrane-spanning region. This structure revealed for the first time how small molecules interact with this entire receptor family at the atomic level, potentially accelerating the development of new drugs for stress-related and metabolic disorders.","specificNumbers":"","methodology":"The researchers used X-ray crystallography to determine the three-dimensional atomic structure of the transmembrane (signal-transducing) domain of the human corticotropin-releasing factor receptor type 1 (CRF1R). The receptor was crystallized in complex with CP-376395, a small-molecule antagonist that binds within the transmembrane region. The structure was expressed and purified from human HEK293 cells.","limitations":"The crystal structure captures the receptor in a single, static conformation bound to an antagonist — it does not show the dynamic conformational changes that occur during receptor activation by peptide hormones. The transmembrane domain was crystallized without the extracellular domain, so the full picture of how peptide hormones bind and activate the complete receptor is incomplete. Crystal packing conditions may not perfectly reflect the receptor's natural membrane environment."},{"rthcId":"RPEP-02196","title":"Incretin hormones and the satiation signal.","authors":"Holst, J J","year":2013,"journal":"International journal of obesity (2005), 37(9), 1161-8","doi":"10.1038/ijo.2012.208","pmid":"23295502","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 is involved in both peripheral and central pathways mediating satiation — it works through gut nerve signals and direct brain effects to reduce food intake. Studies indicate that GLP-1 levels and meal responses may be altered in obese individuals, potentially contributing to overeating.\n\nClinical trials showed that two GLP-1 receptor agonists, exenatide and liraglutide (both approved for type 2 diabetes), produce weight loss in overweight subjects without diabetes. This established GLP-1 RAs as potential pharmacological treatments for obesity, a direction that has since been validated with the approval of higher-dose liraglutide (Saxenda) and semaglutide (Wegovy) specifically for weight management.","whyItMatters":"This review, written by one of the leading GLP-1 researchers, laid out the scientific rationale for using GLP-1 receptor agonists to treat obesity — years before semaglutide (Wegovy/Ozempic) became a global phenomenon. Understanding how incretin peptides control appetite is foundational to one of the most important drug class developments in modern medicine. The insights about altered GLP-1 responses in obesity help explain why these drugs can be so effective.","specificNumbers":"","methodology":"This is a narrative review synthesizing evidence from physiological studies of GLP-1's role in appetite regulation, observational studies of GLP-1 levels in obesity, and clinical trials of GLP-1 receptor agonists for weight loss. The author, J.J. Holst, is one of the pioneers of GLP-1 research.","limitations":"As a 2013 review, it predates much of the clinical evidence now available for obesity treatment with GLP-1 RAs. Only exenatide and liraglutide were discussed, as semaglutide and tirzepatide had not yet completed obesity trials. The abstract does not provide specific weight loss numbers from the cited clinical trials. The mechanisms of GLP-1-mediated satiation described have since been refined with newer research."},{"rthcId":"RPEP-02197","title":"Pathophysiology of GHRH-growth hormone-IGF1 axis in HIV/AIDS.","authors":"Jain, Shobhit; Desai, Ninad; Bhangoo, Amrit","year":2013,"journal":"Reviews in endocrine & metabolic disorders, 14(2), 113-8","doi":"10.1007/s11154-013-9245-9","pmid":"23657561","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Two distinct disruptions of the GHRH-GH-IGF1 axis occur in HIV/AIDS:\n\n1. HIV lipodystrophy (associated with HAART): Suppressed GH production due to increased somatostatin tone, decreased ghrelin, elevated free fatty acids, and insulin resistance. Results in chronic inflammation, lipid abnormalities, and excess abdominal fat.\n\n2. AIDS wasting syndrome: Elevated GH but low IGF-1 levels, indicating GH resistance — the body produces growth hormone but cannot respond to it properly.\n\nTesamorelin, a GHRH analog, is the only FDA-approved treatment for HIV-associated lipodystrophy, working by restoring GH pulsatility to reduce visceral adipose tissue.","whyItMatters":"HIV-associated lipodystrophy affects a significant proportion of people on antiretroviral therapy and carries real cardiovascular risk from excess visceral fat, insulin resistance, and lipid abnormalities. Understanding the peptide hormone mechanisms involved — somatostatin, ghrelin, GHRH, GH, and IGF-1 — explains why tesamorelin works and guides management of these metabolic complications.","specificNumbers":"","methodology":"This is a narrative review article summarizing the pathophysiology of growth hormone axis disruption in HIV/AIDS, drawing on published clinical and mechanistic research.","limitations":"As a review article, this doesn't present original data. Published in 2013, some treatment paradigms and antiretroviral regimens discussed may have evolved. The review notes that long-term clinical data on tesamorelin was still needed at the time of writing. Individual patient responses to GH axis disruption vary significantly."},{"rthcId":"RPEP-02198","title":"Biochemical and metabolic mechanisms by which dietary whey protein may combat obesity and Type 2 diabetes.","authors":"Jakubowicz, Daniela; Froy, Oren","year":2013,"journal":"The Journal of nutritional biochemistry, 24(1), 1-5","doi":"10.1016/j.jnutbio.2012.07.008","pmid":"22995389","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02199","title":"High caloric intake at breakfast vs. dinner differentially influences weight loss of overweight and obese women.","authors":"Jakubowicz, Daniela; Barnea, Maayan; Wainstein, Julio; Froy, Oren","year":2013,"journal":"Obesity (Silver Spring, Md.), 21(12), 2504-12","doi":"10.1002/oby.20460","pmid":"23512957","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02200","title":"Salutary effect of gastric pentadecapeptide BPC 157 in two different stress urinary incontinence models in female rats.","authors":"Jandric, Ivan; Vrcic, Hrvoje; Jandric Balen, Marica; Kolenc, Danijela; Brcic, Luka; Radic, Bozo; Drmic, Domagoj; Seiwerth, Sven; Sikiric, Predrag","year":2013,"journal":"Medical science monitor basic research, 19, 93-102","doi":"10.12659/MSMBR.883828","pmid":"23478678","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"All BPC-157 treatment regimens counteracted the decrease in leak point pressure (LPP) in both transabdominal urethrolysis (TU) and vaginal dilatation (VD) rat models of stress urinary incontinence. At the 10 µg/kg intraperitoneal and oral doses, BPC-157-treated TU-rats and VD-rats achieved LPP values equivalent to healthy controls.\n\nImmunohistochemical analysis revealed higher desmin (skeletal muscle marker), smooth muscle actin, and CD34 (angiogenesis marker) positivity in the urethral walls of BPC-157-treated rats compared to controls. Muscle-to-connective tissue ratios were also preserved. Notably, BPC-157 did not alter LPP in healthy rats, suggesting its effects are specific to injured tissue.","whyItMatters":"Stress urinary incontinence affects millions of women, often after childbirth or surgery, and current treatments are limited. This study suggests BPC-157 could promote healing of the muscle and tissue structures that control urinary function, potentially offering a new therapeutic approach — especially notable because the peptide worked both by injection and orally.","specificNumbers":"","methodology":"Female Wistar rats underwent either transabdominal urethrolysis or prolonged vaginal dilatation to induce stress urinary incontinence. Over 7 days, rats received BPC-157 intraperitoneally (10 µg/kg or 10 ng/kg daily) or orally in drinking water (10 µg/kg, 0.16 µg/mL). Leak point pressure was tested at day 7. Vesicourethral tissue was harvested for immunohistochemical evaluation of muscle markers, angiogenesis markers, and muscle/connective tissue ratios using Mallory's trichrome staining.","limitations":"This was an animal study in rats, so results may not directly translate to humans. The sample sizes per group were not explicitly stated, and the 7-day treatment period is short. Leak point pressure is a functional measure but may not fully capture the complexity of human stress urinary incontinence. No dose-response curve was established, and long-term effects were not assessed."},{"rthcId":"RPEP-02201","title":"Suppression of the proliferation of human U-87 MG glioblastoma cells by new antagonists of growth hormone-releasing hormone in vivo and in vitro.","authors":"Jaszberenyi, Miklos; Schally, Andrew V; Block, Norman L; Zarandi, Marta; Cai, Ren-Zhi; Vidaurre, Irving; Szalontay, Luca; Jayakumar, Arumugam R; Rick, Ferenc G","year":2013,"journal":"Targeted oncology, 8(4), 281-90","doi":"10.1007/s11523-013-0264-y","pmid":"23371031","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02202","title":"GLP-1 agonists for type 2 diabetes: pharmacokinetic and toxicological considerations.","authors":"Jespersen, Maria J; Knop, Filip K; Christensen, Mikkel","year":2013,"journal":"Expert opinion on drug metabolism & toxicology, 9(1), 17-29","doi":"10.1517/17425255.2013.731394","pmid":"23094590","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02203","title":"The clinical utility of C-peptide measurement in the care of patients with diabetes.","authors":"Jones, A G; Hattersley, A T","year":2013,"journal":"Diabetic medicine : a journal of the British Diabetic Association, 30(7), 803-17","doi":"10.1111/dme.12159","pmid":"23413806","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02204","title":"Collagen stimulating effect of peptide amphiphile C16-KTTKS on human fibroblasts.","authors":"Jones, Roanne R; Castelletto, Valeria; Connon, Che J; Hamley, Ian W","year":2013,"journal":"Molecular pharmaceutics, 10(3), 1063-9","doi":"10.1021/mp300549d","pmid":"23320752","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02205","title":"NAP (davunetide) modifies disease progression in a mouse model of severe neurodegeneration: protection against impairments in axonal transport.","authors":"Jouroukhin, Yan; Ostritsky, Regina; Assaf, Yaniv; Pelled, Galit; Giladi, Eliezer; Gozes, Illana","year":2013,"journal":"Neurobiology of disease, 56, 79-94","doi":"10.1016/j.nbd.2013.04.012","pmid":"23631872","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02206","title":"Independent and combined effects of eating rate and energy density on energy intake, appetite, and gut hormones.","authors":"Karl, J Philip; Young, Andrew J; Rood, Jennifer C; Montain, Scott J","year":2013,"journal":"Obesity (Silver Spring, Md.), 21(3), E244-52","doi":"10.1002/oby.20075","pmid":"23592679","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02207","title":"Lacritin and the tear proteome as natural replacement therapy for dry eye.","authors":"Karnati, Roy; Laurie, Diane E; Laurie, Gordon W","year":2013,"journal":"Experimental eye research, 117, 39-52","doi":"10.1016/j.exer.2013.05.020","pmid":"23769845","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Lacritin and lipocalin-1 are two tear proteins selectively deficient in dry eye disease. Lacritin is a prosecretory mitogen — meaning it both stimulates tear secretion and promotes cell growth — and has been shown to promote basal tearing when applied topically as a recombinant protein.\n\nActive monomeric lacritin levels are suppressed by tear tissue transglutaminase, an enzyme whose expression is elevated in dry eye patients with ocular surface inflammation. Lipocalin-1 serves as the primary lipid-absorbing molecule of the tear film, preventing residual lipids from disrupting the eye surface wetting layer. It also functions as a carrier for vitamins and steroid hormones and as an endonuclease that clears potentially proinflammatory DNA from tears.","whyItMatters":"Current dry eye treatments are largely palliative, offering temporary relief without targeting the root cause. Identifying specific tear proteins that are depleted in dry eye opens the door to biotherapeutic approaches that could restore normal tear function rather than simply masking symptoms. This research shifts the treatment paradigm from generic lubrication to precision replacement of missing biological components.","specificNumbers":"","methodology":"This was a narrative review examining the tear proteome — the complete set of proteins found in tears — with a focus on lacritin and lipocalin-1 biology. The authors synthesized findings from proteomic studies, functional assays, and preclinical experiments to discuss the therapeutic potential of tear protein replacement.","limitations":"This is a review article, not a clinical trial, so it synthesizes existing evidence rather than presenting new patient data. The therapeutic potential of topical lacritin has been demonstrated in preclinical models but had not yet been validated in large-scale human clinical trials at the time of publication. The specific mechanisms by which protein-protein interactions in the tear film affect function are not fully understood."},{"rthcId":"RPEP-02208","title":"Food reward-sensitive interaction of ghrelin and opioid receptor pathways in mesolimbic dopamine system.","authors":"Kawahara, Yukie; Kaneko, Fumi; Yamada, Makiko; Kishikawa, Yuki; Kawahara, Hiroshi; Nishi, Akinori","year":2013,"journal":"Neuropharmacology, 67, 395-402","doi":"10.1016/j.neuropharm.2012.11.022","pmid":"23220294","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02209","title":"The effect of glucagon-like peptide-1 receptor agonist therapy on body mass index in adolescents with severe obesity: a randomized, placebo-controlled, clinical trial.","authors":"Kelly, Aaron S; Rudser, Kyle D; Nathan, Brandon M; Fox, Claudia K; Metzig, Andrea M; Coombes, Brandon J; Fitch, Angela K; Bomberg, Eric M; Abuzzahab, M Jennifer","year":2013,"journal":"JAMA pediatrics, 167(4), 355-60","doi":"10.1001/jamapediatrics.2013.1045","pmid":"23380890","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02210","title":"Peripheral antinociceptive efficacy and potency of a novel opioid compound 14-O-MeM6SU in comparison to known peptide and non-peptide opioid agonists in a rat model of inflammatory pain.","authors":"Khalefa, Baled I; Mousa, Shaaban A; Shaqura, Mohammed; Lackó, Erzsébet; Hosztafi, Sándor; Riba, Pál; Schäfer, Michael; Ferdinandy, Péter; Fürst, Susanna; Al-Khrasani, Mahmoud","year":2013,"journal":"European journal of pharmacology, 713(1-3), 54-7","doi":"10.1016/j.ejphar.2013.04.043","pmid":"23665110","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"When administered locally into inflamed paws, the maximal analgesic effect was highest for 14-O-MeM6SU (50.6%), followed by β-endorphin (40.69%), fentanyl (37.44%), met-enkephalin (36.00%), and morphine (18.23%). The novel compound was more potent than all comparators.\n\nNatural opioid peptides (met-enkephalin and β-endorphin) displayed a peripheral analgesic ceiling effect — they could not produce analgesia beyond a certain level — and their effects were confined to inflamed tissue. In contrast, at higher doses, 14-O-MeM6SU, morphine, and fentanyl also produced effects in non-inflamed tissue. All analgesic effects were reversed by the opioid antagonist naloxone-methiodide, confirming opioid receptor mediation.","whyItMatters":"Developing locally acting pain relievers that work at the site of inflammation could provide effective pain control without the systemic side effects (addiction, respiratory depression, sedation) of traditional opioids. Understanding how natural opioid peptides compare to synthetic compounds in peripheral pain relief helps guide the design of safer analgesics.","specificNumbers":"","methodology":"Inflammatory pain was induced in rat hind paws using Freund's complete adjuvant. Opioid compounds were injected directly into the paw (intraplantar), and pain thresholds were measured using pressure paw-withdrawal testing. Five compounds were compared: the novel 14-O-MeM6SU, morphine, fentanyl, met-enkephalin, and β-endorphin. In vitro potency was also assessed using the rat vas deferens bioassay. The opioid antagonist naloxone-methiodide confirmed receptor specificity.","limitations":"This is an animal study in rats, and results may not translate directly to human pain management. The study focused on acute inflammatory pain from a single model; chronic pain responses may differ. The novel compound 14-O-MeM6SU has not been tested in humans. The ceiling effect of opioid peptides at the periphery needs further mechanistic investigation."},{"rthcId":"RPEP-02211","title":"Stable gastric pentadecapeptide BPC 157 heals cysteamine-colitis and colon-colon-anastomosis and counteracts cuprizone brain injuries and motor disability.","authors":"Klicek, R; Kolenc, D; Suran, J; Drmic, D; Brcic, L; Aralica, G; Sever, M; Holjevac, J; Radic, B; Turudic, T; Kokot, A; Patrlj, L; Rucman, R; Seiwerth, S; Sikiric, P","year":2013,"journal":"Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 64(5), 597-612","doi":null,"pmid":"24304574","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02212","title":"Role of neuropeptides in anxiety, stress, and depression: from animals to humans.","authors":"Kormos, Viktória; Gaszner, Balázs","year":2013,"journal":"Neuropeptides, 47(6), 401-19","doi":"10.1016/j.npep.2013.10.014","pmid":"24210138","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies multiple neuropeptide systems involved in mood regulation: corticotropin-releasing factor (CRF) and its related urocortins drive the stress response and are overactive in depression; neuropeptide Y appears to be protective against anxiety and stress; oxytocin has anxiolytic properties; substance P (via NK1 receptors) promotes anxiety and emotional distress; neuropeptide S promotes wakefulness and reduces anxiety; and PACAP modulates stress responses.\n\nThe central argument is that because current monoamine-targeting drugs fail a significant proportion of patients, these neuropeptide systems represent promising alternative or complementary therapeutic targets.","whyItMatters":"Depression is the leading cause of disability worldwide, and a large percentage of patients don't improve with existing medications. Understanding how neuropeptides contribute to mood disorders opens entirely new avenues for drug development. Rather than tweaking serotonin or norepinephrine levels, future treatments could target the brain's peptide signaling systems more directly.","specificNumbers":"","methodology":"This is a narrative review article summarizing published research from animal models of mood disorders (including genetically modified rodent models), preclinical pharmacology studies, and available clinical data across 11 neuropeptide systems.","limitations":"Most evidence cited comes from animal models, which don't perfectly replicate human psychiatric conditions. The review was published in 2013 and doesn't cover more recent clinical trials targeting these neuropeptide systems. The complexity of neuropeptide interactions makes it difficult to predict which targets will prove most clinically useful."},{"rthcId":"RPEP-02213","title":"Effects of intrathecal SNC80, a delta receptor ligand, on nociceptive threshold and dorsal horn substance p release.","authors":"Kouchek, Milad; Takasusuki, Toshifumi; Terashima, Tetsuji; Yaksh, Tony L; Xu, Qinghao","year":2013,"journal":"The Journal of pharmacology and experimental therapeutics, 347(2), 258-64","doi":"10.1124/jpet.113.206573","pmid":"23978562","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02214","title":"Long-term three-dimensional neural tissue cultures in functionalized self-assembling peptide hydrogels, matrigel and collagen I.","authors":"Koutsopoulos, Sotirios; Zhang, Shuguang","year":2013,"journal":"Acta biomaterialia, 9(2), 5162-9","doi":"10.1016/j.actbio.2012.09.010","pmid":"22995405","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02215","title":"Bacterial expression, purification and angiogenesis-promoting activity of human thymosin β4.","authors":"Kozaczuk, Anna; Selmi, Anna; Bednarek, Radoslaw","year":2013,"journal":"Protein expression and purification, 90(2), 142-52","doi":"10.1016/j.pep.2013.06.003","pmid":"23769831","tags":[],"studyType":"in-vitro","evidenceStrength":"low","keyFinding":"Researchers successfully produced recombinant thymosin β4 (Tβ4) in bacteria (E. coli) and demonstrated that this lab-made version promoted angiogenesis (new blood vessel formation) just as effectively as the expensive chemically synthesized version. The recombinant Tβ4 activated endothelial cell proteolytic systems, inhibited cell adhesion, promoted cell migration, and stimulated capillary tube formation in Matrigel.\n\nThis was the first evidence that bacterially produced recombinant Tβ4 retains its angiogenesis-promoting activity in an in vitro endothelial cell model — proving it can replace costly synthetic peptide for research and potentially clinical applications.","whyItMatters":"Thymosin β4 is a promising peptide for wound healing and tissue regeneration, but its production via chemical synthesis is expensive and limits research and clinical development. Showing that a cheap bacterial production method yields equally active peptide removes a major barrier to scaling up Tβ4 research and could make future clinical applications more affordable.","specificNumbers":"43 amino acids (Tβ4 length) · 3 expression vectors tested · 2-step purification · Activity equivalent to synthetic peptide","methodology":"The team cloned human thymosin β4 into three different bacterial expression vectors and produced the peptide in protease-deficient E. coli BL21(DE3) bacteria. The recombinant peptide was purified using two-step immobilized metal ion affinity chromatography. The polyhistidine tag was removed using thrombin cleavage. Functional activity was tested in vitro using endothelial cell assays measuring proteolytic activity, cell adhesion, migration, and capillary tube formation in Matrigel.","limitations":"This is entirely an in vitro (lab dish) study — no animal or human testing was performed. Equivalent activity in cell culture doesn't guarantee equivalent therapeutic activity in a living organism. The study is from 2013 and it's unclear whether this production method has been adopted or further validated. Glycosylation differences between bacterial and mammalian production could matter for some applications."},{"rthcId":"RPEP-02216","title":"Incretin-based therapies in the treatment of type 2 diabetes--more than meets the eye?","authors":"Labuzek, Krzysztof; Kozłowski, Michał; Szkudłapski, Dawid; Sikorska, Patrycja; Kozłowska, Monika; Okopień, Bogusław","year":2013,"journal":"European journal of internal medicine, 24(3), 207-12","doi":"10.1016/j.ejim.2013.01.009","pmid":"23375875","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02217","title":"Adolescent binge-like ethanol exposure reduces basal α-MSH expression in the hypothalamus and the amygdala of adult rats.","authors":"Lerma-Cabrera, Jose Manuel; Carvajal, Francisca; Alcaraz-Iborra, Manuel; de la Fuente, Leticia; Navarro, Montserrat; Thiele, Todd E; Cubero, Inmaculada","year":2013,"journal":"Pharmacology, biochemistry, and behavior, 110, 66-74","doi":"10.1016/j.pbb.2013.06.006","pmid":"23792540","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Binge-like ethanol exposure during adolescence significantly reduced basal α-MSH (a melanocortin neuropeptide) levels in three key brain regions — the central nucleus of the amygdala (CeA), arcuate nucleus (Arc), and paraventricular nucleus (PVN) — in adult rats 25 days after the last ethanol exposure. Acute ethanol also increased AgRP (the melanocortin inverse agonist) in the Arc, and adolescent-exposed rats required higher ethanol doses to elicit this AgRP response. These lasting neuropeptide disturbances may contribute to excessive adult alcohol consumption.","whyItMatters":"Adolescent binge drinking is a major public health concern linked to adult alcohol problems. This study identifies a specific neuropeptide mechanism — lasting suppression of α-MSH melanocortin signaling — that could explain why early alcohol exposure predisposes to adult addiction. Understanding this peptide pathway could inform prevention strategies and potential therapeutic targets.","specificNumbers":"Ethanol: 3.0 g/kg i.p. · 8 total injections over adolescence · 25 ethanol-free days before testing · reduced α-MSH in CeA, Arc, and PVN · AgRP increased in Arc","methodology":"Adolescent Sprague-Dawley rats (starting PND25) received binge-like ethanol (3.0 g/kg i.p.) or saline in a pattern of 2 days on, 2 days off, for 8 total injections. After 25 ethanol-free days (adulthood, PND63), rats received acute ethanol (1.5 or 3.0 g/kg) or saline. α-MSH and AgRP immunoreactivity was measured in hypothalamic and limbic brain nuclei.","limitations":"Rat model — adolescent brain development differs from humans. Intraperitoneal ethanol injection doesn't mimic voluntary drinking behavior. Only male rats were studied. The causal link between α-MSH reduction and increased drinking behavior was speculated but not directly demonstrated. The study measured peptide levels at one time point only."},{"rthcId":"RPEP-02218","title":"Changes of substance P in the crevicular fluid in relation to orthodontic movement preliminary investigation.","authors":"Levrini, Luca; Sacerdote, Paola; Moretti, Sarah; Panzi, Silvia; Caprioglio, Alberto","year":2013,"journal":"TheScientificWorldJournal, 2013, 896874","doi":"10.1155/2013/896874","pmid":"23737731","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Substance P (SP), a pain-signaling neuropeptide, was detected in the gingival crevicular fluid of teeth undergoing orthodontic movement with the Invisalign technique, but was not found in control teeth from the same patients that were not being moved. This is one of the first studies to demonstrate substance P release specifically during clear aligner orthodontic treatment.","whyItMatters":"Understanding the role of neuropeptides like substance P in orthodontic pain and inflammation could lead to better pain management strategies during treatment. Substance P is a key mediator of pain signaling and inflammation, so its presence in gingival fluid during tooth movement confirms that orthodontic forces activate neuropeptide-mediated inflammatory pathways in the periodontal tissues.","specificNumbers":"n=4 subjects · GCF collected with paper cones · 60-second sampling time · SP present in treated teeth · SP absent in control teeth","methodology":"In this pilot study, gingival crevicular fluid (GCF) was collected from four young subjects undergoing Invisalign orthodontic treatment. Paper cones were placed in the gingival sulcus for 60 seconds to collect samples from both teeth being actively moved and control teeth in the same patient that were not undergoing movement. Samples were analyzed for substance P content.","limitations":"This is a very small pilot study with only 4 subjects, making the results preliminary at best. No quantitative substance P measurements are reported — only presence or absence. The study design lacks statistical analysis due to the small sample size. Only the Invisalign technique was tested, and results may differ with other orthodontic methods. The sampling methodology (paper cone absorption) may have limited sensitivity."},{"rthcId":"RPEP-02219","title":"Ghrelin directly stimulates adult hippocampal neurogenesis: implications for learning and memory.","authors":"Li, Endan; Chung, Hyunju; Kim, Yumi; Kim, Dong Hyun; Ryu, Jong Hoon; Sato, Takahiro; Kojima, Masayasu; Park, Seungjoon","year":2013,"journal":"Endocrine journal, 60(6), 781-9","doi":null,"pmid":"23411585","tags":[],"studyType":"animal","evidenceStrength":"preliminary","keyFinding":"Mice lacking the ghrelin gene had fewer progenitor cells in the hippocampus, reduced numbers of immature and newly generated neurons, and impaired memory performance on Y-maze and novel object recognition tests. Administering ghrelin to these knockout mice restored progenitor cell numbers to wild-type levels, increased new neuron formation, and reversed the memory deficits.\n\nThis demonstrates that endogenous ghrelin — not just externally administered ghrelin — plays a direct role in adult hippocampal neurogenesis, and that ghrelin's absence measurably impairs learning and memory.","whyItMatters":"The hippocampus is central to forming new memories, and adult neurogenesis in this region is linked to cognitive function. This study shows ghrelin isn't just a hunger hormone — it directly drives the birth and maturation of new brain cells. If this translates to humans, ghrelin pathways could become therapeutic targets for age-related cognitive decline, neurodegenerative diseases, or conditions where hippocampal neurogenesis is impaired.","specificNumbers":"Ghrelin knockout mice: reduced BrdU+ progenitor cells in SGZ · Reduced immature neurons and newly generated neurons · Impaired Y-maze and novel object recognition · All deficits reversed by ghrelin replacement","methodology":"Researchers used ghrelin knockout (GKO) mice and wild-type controls. They assessed hippocampal progenitor cell proliferation using BrdU labeling, tracked neuronal differentiation with immunohistochemistry, and tested memory using Y-maze spontaneous alternation and novel object recognition tasks. GKO mice then received ghrelin replacement to determine if deficits were reversible.","limitations":"This is an animal study in genetically modified mice, so direct translation to humans is uncertain. The abstract does not provide specific numerical values for cell counts or behavioral scores. Knockout models eliminate ghrelin from development, which may not reflect what happens when ghrelin declines in adulthood or aging. No dose-response data was reported."},{"rthcId":"RPEP-02220","title":"Growth hormone secretagogues exert differential effects on skeletal muscle calcium homeostasis in male rats depending on the peptidyl/nonpeptidyl structure.","authors":"Liantonio, Antonella; Gramegna, Gianluca; Carbonara, Giuseppe; Sblendorio, Valeriana Teresa; Pierno, Sabata; Fraysse, Bodvaël; Giannuzzi, Viviana; Rizzi, Laura; Torsello, Antonio; Camerino, Diana Conte","year":2013,"journal":"Endocrinology, 154(10), 3764-75","doi":"10.1210/en.2013-1334","pmid":"23836033","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02221","title":"Iterative antimicrobial candidate selection from informed d-/l-Peptide dimer libraries.","authors":"Lichtenecker, Roman J; Ellinger, Bernhard; Han, Hong-Mei; Jadhav, Kirtikumar B; Baumann, Sascha; Makarewicz, Oliwia; Grabenbauer, Markus; Arndt, Hans-Dieter","year":2013,"journal":"Chembiochem : a European journal of chemical biology, 14(18), 2492-9","doi":"10.1002/cbic.201300243","pmid":"24151156","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02222","title":"Peritoneal administration of Met-RANTES attenuates inflammatory and nociceptive responses in a murine neuropathic pain model.","authors":"Liou, Jiin-Tarng; Mao, Chih-Chieh; Ching-Wah Sum, Daniel; Liu, Fu-Chao; Lai, Ying-Shu; Li, Jui-Chin; Day, Yuan-Ji","year":2013,"journal":"The journal of pain, 14(1), 24-35","doi":"10.1016/j.jpain.2012.09.015","pmid":"23183003","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Met-RANTES-treated mice showed significantly less behavioral hypersensitivity (pain) after partial sciatic nerve ligation. At the molecular level, treatment significantly reduced macrophage infiltration at the injury site, decreased secretion of pro-inflammatory cytokines (TNFα, IL-1β, IL-6, and IFNγ), and increased anti-inflammatory IL-10 levels.\n\nExpression of opioid peptides — enkephalin, β-endorphin, and dynorphin mRNA — in damaged nerves was also significantly decreased in treated mice, suggesting that reducing inflammation reduced the compensatory opioid peptide response. The results demonstrate that CCL5 regulates the inflammatory microenvironment controlling pain sensitivity at the peripheral nerve injury site.","whyItMatters":"Neuropathic pain is notoriously difficult to treat, and current therapies are often inadequate or carry addiction risks. This study identifies CCL5 as a key driver of the inflammatory environment that causes pain at nerve injury sites and demonstrates that blocking it with a peptide-based antagonist can reduce both inflammation and pain. This points to a potential new therapeutic strategy for chronic pain.","specificNumbers":"","methodology":"Mice underwent partial sciatic nerve ligation to create a neuropathic pain model. Met-RANTES (a selective CCL5 receptor antagonist) was administered via intraperitoneal injection. Researchers measured behavioral pain responses, quantified immune cell infiltration using flow cytometry and immunohistochemistry, measured cytokine protein levels (TNFα, IL-1β, IL-6, IFNγ, IL-10), and assessed opioid peptide mRNA expression (enkephalin, β-endorphin, dynorphin) using real-time PCR in damaged nerves.","limitations":"The study was conducted in mice, and results may not directly translate to human neuropathic pain. Only peritoneal (systemic) administration was tested, so local delivery effects are unknown. The study used a single neuropathic pain model (partial sciatic nerve ligation), and results may differ in other pain conditions. Long-term effects and potential for immunosuppression with chronic CCL5 blockade were not assessed. Sample sizes were not specified in the abstract."},{"rthcId":"RPEP-02223","title":"Chemical genomic screening of a Saccharomyces cerevisiae genomewide mutant collection reveals genes required for defense against four antimicrobial peptides derived from proteins found in human saliva.","authors":"Lis, Maciej; Bhatt, Sanjay; Schoenly, Nathan E; Lee, Anna Y; Nislow, Corey; Bobek, Libuse A","year":2013,"journal":"Antimicrobial agents and chemotherapy, 57(2), 840-7","doi":"10.1128/AAC.01439-12","pmid":"23208710","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02224","title":"Generation of mature Nα-terminal acetylated thymosin α 1 by cleavage of recombinant prothymosin α.","authors":"Liu, Bo; Gong, Xin; Chang, Shaohong; Sun, Peng; Wu, Jun","year":2013,"journal":"TheScientificWorldJournal, 2013, 387282","doi":"10.1155/2013/387282","pmid":"24288480","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02225","title":"Functionalized self-assembling peptide nanofiber hydrogels mimic stem cell niche to control human adipose stem cell behavior in vitro.","authors":"Liu, Xi; Wang, Xiumei; Wang, Xiujuan; Ren, Hui; He, Jin; Qiao, Lin; Cui, Fu-Zhai","year":2013,"journal":"Acta biomaterialia, 9(6), 6798-805","doi":"10.1016/j.actbio.2013.01.027","pmid":"23380207","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02226","title":"Recent and emerging therapeutic medications in type 2 diabetes mellitus: incretin-based, Pramlintide, Colesevelam, SGLT2 Inhibitors, Tagatose, Succinobucol.","authors":"Lo, Margaret C; Lansang, M Cecilia","year":2013,"journal":"American journal of therapeutics, 20(6), 638-53","doi":"10.1097/MJT.0b013e3181ec9eb2","pmid":"20838206","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02227","title":"Secondary photocrosslinking of injectable shear-thinning dock-and-lock hydrogels.","authors":"Lu, Hoang D; Soranno, Danielle E; Rodell, Christopher B; Kim, Iris L; Burdick, Jason A","year":2013,"journal":"Advanced healthcare materials, 2(7), 1028-36","doi":"10.1002/adhm.201200343","pmid":"23299998","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02228","title":"Associations between the oxytocin receptor gene (OXTR) and \"mind-reading\" in humans--an exploratory study.","authors":"Lucht, Michael J; Barnow, Sven; Sonnenfeld, Christine; Ulrich, Ines; Grabe, Hans Joergen; Schroeder, Winnie; Völzke, Henry; Freyberger, Harald J; John, Ulrich; Herrmann, Falko H; Kroemer, Heyo; Rosskopf, Dieter","year":2013,"journal":"Nordic journal of psychiatry, 67(1), 15-21","doi":"10.3109/08039488.2012.700731","pmid":"22809402","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02229","title":"Antigen-specific tolerance by autologous myelin peptide-coupled cells: a phase 1 trial in multiple sclerosis.","authors":"Lutterotti, Andreas; Yousef, Sara; Sputtek, Andreas; Stürner, Klarissa H; Stellmann, Jan-Patrick; Breiden, Petra; Reinhardt, Stefanie; Schulze, Christian; Bester, Maxim; Heesen, Christoph; Schippling, Sven; Miller, Stephen D; Sospedra, Mireia; Martin, Roland","year":2013,"journal":"Science translational medicine, 5(188), 188ra75","doi":"10.1126/scitranslmed.3006168","pmid":"23740901","tags":["peptide-vaccine","immune-tolerance"],"studyType":"phase-1-clinical-trial","evidenceStrength":"preliminary-clinical","keyFinding":"All nine patients tolerated the peptide-coupled cell infusion without serious adverse events. Patients receiving higher doses (more than 1 billion peptide-coupled cells) showed a measurable decrease in T cell reactivity against the myelin peptides used in the therapy.\n\nThis is significant because it suggests the treatment achieved its intended mechanism — reducing the specific immune response against myelin without broadly suppressing immunity. The therapy was feasible to manufacture from each patient's own blood cells and the seven myelin peptides covered multiple autoimmune targets simultaneously.","whyItMatters":"Current MS treatments broadly suppress the immune system, which controls the disease but leaves patients vulnerable to infections and cancers. Antigen-specific tolerance — teaching the immune system to stop attacking just the myelin targets — would be a paradigm shift, treating the root cause while leaving the rest of immunity intact. This trial is the first demonstration that this approach is feasible and safe in human MS patients.","specificNumbers":"n=9; 7 myelin peptides; doses up to >1×10⁹ cells; decreased T cell reactivity at higher doses","methodology":"Open-label, single-center, dose-escalation phase 1 trial. Nine MS patients (7 relapsing-remitting, 2 secondary progressive) off standard therapies received a single intravenous infusion of their own blood cells chemically coupled with seven myelin peptides. Safety, tolerability, and immune responses were monitored through neurological exams, MRI, laboratory tests, and immunological assessments.","limitations":"Phase 1 safety trial only; n=9; no control group; open-label; single center; patients off standard therapy; clinical efficacy not assessed; long-term durability unknown."},{"rthcId":"RPEP-02230","title":"Construction of an expression vector for production and purification of human somatostatin in Escherichia coli.","authors":"Maicas, Sergi; Moukadiri, Ismaïl; Nieto, Almudena; Valentín, Eulogio","year":2013,"journal":"Molecular biotechnology, 55(2), 150-8","doi":"10.1007/s12033-013-9667-3","pmid":"23640683","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02231","title":"Egg-derived tri-peptide IRW exerts antihypertensive effects in spontaneously hypertensive rats.","authors":"Majumder, Kaustav; Chakrabarti, Subhadeep; Morton, Jude S; Panahi, Sareh; Kaufman, Susan; Davidge, Sandra T; Wu, Jianping","year":2013,"journal":"PloS one, 8(11), e82829","doi":"10.1371/journal.pone.0082829","pmid":"24312436","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Oral administration of the egg-derived tripeptide IRW (Ile-Arg-Trp) to spontaneously hypertensive rats (SHRs) reduced mean blood pressure by approximately 10 mmHg at 3 mg/kg and 40 mmHg at 15 mg/kg over 18 days of daily dosing.\n\nThe blood pressure reduction was accompanied by restoration of normal circadian blood pressure patterns, preservation of nitric oxide-dependent vasorelaxation, decreased plasma angiotensin II levels, reduced inflammatory markers, and less tissue fibrosis — all without changes in heart rate.","whyItMatters":"Finding food-derived peptides that can lower blood pressure could lead to functional foods or supplements for managing hypertension with fewer side effects than pharmaceutical drugs. This study is notable because IRW works through multiple mechanisms simultaneously — ACE inhibition, nitric oxide support, and anti-inflammation — which mirrors the complex pathology of hypertension better than single-target drugs.","specificNumbers":"","methodology":"Male spontaneously hypertensive rats (16–17 weeks old) were given oral IRW at either a low dose (3 mg/kg body weight) or high dose (15 mg/kg) daily for 18 days, with untreated SHRs as controls. Blood pressure and heart rate were monitored continuously via implanted telemetry devices. After the treatment period, animals were sacrificed for vascular function studies, and inflammatory markers and tissue fibrosis were measured.","limitations":"This is an animal study using a specific rat model of hypertension (SHR), so results may not translate directly to humans. The study lasted only 18 days, so long-term effects and safety are unknown. Sample sizes per group were not specified in the abstract. The SHR model represents essential hypertension specifically and may not reflect other causes of high blood pressure. Oral bioavailability of the peptide in humans could differ significantly from rats."},{"rthcId":"RPEP-02232","title":"Structure and activity study of egg protein ovotransferrin derived peptides (IRW and IQW) on endothelial inflammatory response and oxidative stress.","authors":"Majumder, Kaustav; Chakrabarti, Subhadeep; Davidge, Sandra T; Wu, Jianping","year":2013,"journal":"Journal of agricultural and food chemistry, 61(9), 2120-9","doi":"10.1021/jf3046076","pmid":"23317476","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02233","title":"Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents.","authors":"McCoy, Alene T; Benoist, Caroline C; Wright, John W; Kawas, Leen H; Bule-Ghogare, Jyote M; Zhu, Mingyan; Appleyard, Suzanne M; Wayman, Gary A; Harding, Joseph W","year":2013,"journal":"The Journal of pharmacology and experimental therapeutics, 344(1), 141-54","doi":"10.1124/jpet.112.199497","pmid":"23055539","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02234","title":"Current and future applications of GnRH, kisspeptin and neurokinin B analogues.","authors":"Millar, Robert P; Newton, Claire L","year":2013,"journal":"Nature reviews. Endocrinology, 9(8), 451-66","doi":"10.1038/nrendo.2013.120","pmid":"23817290","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02235","title":"Once-weekly exenatide: an extended-duration glucagon-like peptide agonist for the treatment of type 2 diabetes mellitus.","authors":"Minze, Molly G; Klein, Mary S; Jernigan, Michelle J; Wise, Stephen L; Frugé, Kristian","year":2013,"journal":"Pharmacotherapy, 33(6), 627-38","doi":"10.1002/phar.1240","pmid":"23553357","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02236","title":"Proteolysis controls endogenous substance P levels.","authors":"Mitchell, Andrew J; Lone, Anna Mari; Tinoco, Arthur D; Saghatelian, Alan","year":2013,"journal":"PloS one, 8(7), e68638","doi":"10.1371/journal.pone.0068638","pmid":"23894327","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02237","title":"Distinct physiological role of amidino-TAPA-sensitive and DAMGO-insensitive μ-opioid receptor splice variants in the mouse spinal cord.","authors":"Mizoguchi, Hirokazu; Watanabe, Chizuko; Higashiya, Takayuki; Takeda, Satoshi; Moriyama, Kaori; Aoki, Yuta; Kon-no, Takashi; Takagi, Hirokazu; Yonezawa, Akihiko; Sato, Takumi; Sakurada, Tsukasa; Sakurada, Shinobu","year":2013,"journal":"European journal of pharmacology, 711(1-3), 80-6","doi":"10.1016/j.ejphar.2013.04.014","pmid":"23623932","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02238","title":"Crohn's disease affecting the small bowel is associated with reduced appetite and elevated levels of circulating gut peptides.","authors":"Moran, Gordon W; Leslie, Fiona C; McLaughlin, John T","year":2013,"journal":"Clinical nutrition (Edinburgh, Scotland), 32(3), 404-11","doi":"10.1016/j.clnu.2012.08.024","pmid":"22999064","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02239","title":"Davunetide: a review of safety and efficacy data with a focus on neurodegenerative diseases.","authors":"Morimoto, Bruce H; Fox, Anthony W; Stewart, Alistair J; Gold, Michael","year":2013,"journal":"Expert review of clinical pharmacology, 6(5), 483-502","doi":"10.1586/17512433.2013.827403","pmid":"23971871","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02240","title":"Pathophysiology of the anorexia of aging.","authors":"Morley, John E","year":2013,"journal":"Current opinion in clinical nutrition and metabolic care, 16(1), 27-32","doi":"10.1097/MCO.0b013e328359efd7","pmid":"23041615","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02241","title":"The 1,2,4-triazole as a scaffold for the design of ghrelin receptor ligands: development of JMV 2959, a potent antagonist.","authors":"Moulin, Aline; Brunel, Luc; Boeglin, Damien; Demange, Luc; Ryan, Johanne; M'Kadmi, Céline; Denoyelle, Séverine; Martinez, Jean; Fehrentz, Jean-Alain","year":2013,"journal":"Amino acids, 44(2), 301-14","doi":"10.1007/s00726-012-1355-2","pmid":"22798076","tags":[],"studyType":"review","evidenceStrength":"moderate","keyFinding":"This article describes the peptidomimetic design process that led to JMV 2959, a potent ghrelin receptor (GHS-R1a) antagonist built on a 1,2,4-triazole scaffold. Starting from the 28-amino-acid ghrelin peptide, the researchers progressively simplified the structure through medicinal chemistry to create a small-molecule antagonist. JMV 2959 has been extensively studied across multiple biological contexts, showing effects on food intake and obesity, addictive behaviors (including alcohol, nicotine, and drug reward), hyperactivity, and retinopathy.","whyItMatters":"Ghrelin is a key peptide hormone regulating appetite, metabolism, and reward pathways. JMV 2959 has become one of the most widely used research tools for studying ghrelin receptor function, and its development from a natural peptide to a drug-like small molecule illustrates the power of peptidomimetic design. The compound's effects on addiction are particularly noteworthy, as they suggest ghrelin signaling plays a role in reward-seeking behavior beyond food.","specificNumbers":"","methodology":"Peptidomimetic medicinal chemistry approach starting from the ghrelin peptide sequence and progressively modifying the structure to identify key pharmacophore elements. The 1,2,4-triazole was identified as a versatile scaffold for generating GHS-R1a ligands. JMV 2959 was then characterized in multiple in vitro binding assays and in vivo models covering food intake, addiction, hyperactivity, and retinopathy.","limitations":"This is a highlight/review article describing prior work rather than presenting new data. JMV 2959 remains a research tool compound and has not advanced to clinical trials. The compound's effects across diverse biological models make it a valuable research tool but raise questions about selectivity and potential off-target effects."},{"rthcId":"RPEP-02242","title":"Inhibitory effects of antagonists of growth hormone-releasing hormone on growth and invasiveness of PC3 human prostate cancer.","authors":"Muñoz-Moreno, Laura; Arenas, M Isabel; Schally, Andrew V; Fernández-Martínez, Ana B; Zarka, Elías; González-Santander, Marta; Carmena, María J; Vacas, Eva; Prieto, Juan C; Bajo, Ana M","year":2013,"journal":"International journal of cancer, 132(4), 755-65","doi":"10.1002/ijc.27716","pmid":"22777643","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02243","title":"Growth hormone releasing hormone (GHRH) signaling modulates intermittent hypoxia-induced oxidative stress and cognitive deficits in mouse.","authors":"Nair, Deepti; Ramesh, Vijay; Li, Richard C; Schally, Andrew V; Gozal, David","year":2013,"journal":"Journal of neurochemistry, 127(4), 531-40","doi":"10.1111/jnc.12360","pmid":"23815362","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02244","title":"Interaction of synthetic peptide octarphin with human blood lymphocytes.","authors":"Nekrasova, Yu N; Zolotarev, Yu A; Navolotskaya, E V","year":2013,"journal":"Biochemistry. Biokhimiia, 78(3), 309-13","doi":"10.1134/S0006297913030140","pmid":"23586726","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02245","title":"Interaction of synthetic peptide octarphin (TPLVTLFK) with human blood lymphocytes.","authors":"Nekrasova, Yuliia N; Navolotskaya, Elena V","year":2013,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 19(8), 499-503","doi":"10.1002/psc.2527","pmid":"23794487","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02246","title":"Cationic antimicrobial peptide LL-37 is effective against both extra- and intracellular Staphylococcus aureus.","authors":"Noore, Jabeen; Noore, Adly; Li, Bingyun","year":2013,"journal":"Antimicrobial agents and chemotherapy, 57(3), 1283-90","doi":"10.1128/AAC.01650-12","pmid":"23274662","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"LL-37 was effective at killing extracellular S. aureus at nanomolar concentrations, while lactoferricin B required micromolar concentrations and the conventional antibiotics doxycycline and cefazolin required millimolar concentrations — a potency difference of roughly three orders of magnitude.\n\nCritically, LL-37 was superior to conventional antibiotics at eliminating intracellular S. aureus within osteoblasts. Kinetic studies showed LL-37 acted rapidly against both extra- and intracellular bacteria. An unexpected finding was that LL-37 killed a clinical S. aureus strain more effectively than a standard laboratory (ATCC) strain, suggesting strong real-world applicability.","whyItMatters":"Intracellular bacterial persistence is a major driver of chronic bone infections (osteomyelitis), prosthetic joint infections, and recurrent Staph infections. Conventional antibiotics frequently fail because they cannot efficiently penetrate host cell membranes to reach hiding bacteria. LL-37's ability to kill both extracellular and intracellular S. aureus at very low concentrations makes it a promising candidate for addressing antibiotic-resistant and recurrent infections — one of the most urgent challenges in modern medicine.","specificNumbers":"","methodology":"The researchers used bacterial killing assays to measure LL-37's extracellular efficacy compared to lactoferricin B, doxycycline, and cefazolin against both an ATCC reference strain and a clinical isolate of S. aureus. An osteoblast infection model was established to test intracellular killing — osteoblasts were infected with S. aureus, then treated with LL-37 or antibiotics, and surviving intracellular bacteria were counted. Kinetic studies tracked the speed of bacterial elimination over time.","limitations":"This is an in vitro study using cell-based models, and results may not directly translate to in vivo efficacy where factors like peptide stability, serum binding, tissue penetration, and host toxicity come into play. LL-37 can be cytotoxic at higher concentrations, and the therapeutic window between antimicrobial efficacy and host cell damage was not thoroughly characterized. The study tested only S. aureus; efficacy against other intracellular pathogens is unknown from this work. The osteoblast model, while relevant to bone infections, represents only one of many tissues where intracellular infection occurs."},{"rthcId":"RPEP-02247","title":"Differential pulsatile secretagogue control of GH secretion in healthy men.","authors":"Norman, Catalina; Miles, John; Bowers, Cyril Y; Veldhuis, Johannes D","year":2013,"journal":"American journal of physiology. Regulatory, integrative and comparative physiology, 304(9), R712-9","doi":"10.1152/ajpregu.00069.2013","pmid":"23485864","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02248","title":"Effects of gastrogastric fistula repair on weight loss and gut hormone levels.","authors":"O'Brien, Ciaran S; Wang, Gary; McGinty, James; Agénor, Keesandra K; Dutia, Roxanne; Colarusso, Antonia; Park, Koji; Koshy, Ninan; Laferrère, Blandine","year":2013,"journal":"Obesity surgery, 23(8), 1294-301","doi":"10.1007/s11695-013-0917-z","pmid":"23549962","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02249","title":"Stabilizing the pro-apoptotic BimBH3 helix (BimSAHB) does not necessarily enhance affinity or biological activity.","authors":"Okamoto, Toru; Zobel, Kerry; Fedorova, Anna; Quan, Clifford; Yang, Hong; Fairbrother, Wayne J; Huang, David C S; Smith, Brian J; Deshayes, Kurt; Czabotar, Peter E","year":2013,"journal":"ACS chemical biology, 8(2), 297-302","doi":"10.1021/cb3005403","pmid":"23151250","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The stapled BimBH3 peptide (BimSAHB), designed to have enhanced α-helical stability and improved binding to pro-survival Bcl-2 proteins, actually showed reduced binding affinity for its targets. The researchers attributed this to disruption of a network of stabilizing intramolecular interactions that exist in the bound state of the native (unstapled) peptide.\n\nFurthermore, cells exposed to BimSAHB did not readily undergo apoptosis, strongly indicating that the stapled peptide is not inherently cell permeable — contradicting a key assumption behind its design as a therapeutic agent.","whyItMatters":"Stapled peptides are a major strategy in peptide drug development, with several candidates in clinical trials. This study provides an important cautionary finding: locking a peptide into its helical shape doesn't always improve binding and can actually make things worse if it disrupts critical interactions needed for target recognition.","specificNumbers":"","methodology":"The researchers used binding affinity measurements to compare stapled and native BimBH3 peptides against pro-survival Bcl-2 proteins. Structural analysis identified the intramolecular interaction networks disrupted by stapling. Cell-based apoptosis assays tested whether the modified peptides could kill cells, indirectly testing cell permeability.","limitations":"The study focused on one specific stapled peptide (BimSAHB) targeting Bcl-2 family proteins, so the findings may not generalize to all stapled peptides. Different staple positions or chemistries might yield different results. The study did not test whether alternative modifications could improve both stability and binding."},{"rthcId":"RPEP-02250","title":"Long-term inhibition of intestinal lipase by orlistat improves release of gut hormones increasing satiety in obese women.","authors":"Olszanecka-Glinianowicz, Magdalena; Dąbrowski, Piotr; Kocełak, Piotr; Janowska, Joanna; Smertka, Mike; Jonderko, Krzysztof; Chudek, Jerzy","year":2013,"journal":"Pharmacological reports : PR, 65(3), 666-71","doi":null,"pmid":"23950589","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02251","title":"Antimicrobial peptides and gut microbiota in homeostasis and pathology.","authors":"Ostaff, Maureen J; Stange, Eduard Friedrich; Wehkamp, Jan","year":2013,"journal":"EMBO molecular medicine, 5(10), 1465-83","doi":"10.1002/emmm.201201773","pmid":"24039130","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02252","title":"Investigation of the metabolic biotransformation of substance P in liver microsomes by liquid chromatography quadrupole ion trap mass spectrometry.","authors":"Pailleux, Floriane; Lemoine, Jérôme; Beaudry, Francis","year":2013,"journal":"Biomedical chromatography : BMC, 27(1), 39-47","doi":"10.1002/bmc.2746","pmid":"22544680","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02253","title":"Effects of rearing conditions on behaviour and endogenous opioids in rats with alcohol access during adolescence.","authors":"Palm, Sara; Daoura, Loudin; Roman, Erika; Nylander, Ingrid","year":2013,"journal":"PloS one, 8(10), e76591","doi":"10.1371/journal.pone.0076591","pmid":"24098535","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02254","title":"Bovine lactoferricin B induces apoptosis of human gastric cancer cell line AGS by inhibition of autophagy at a late stage.","authors":"Pan, W-R; Chen, P-W; Chen, Y-L S; Hsu, H-C; Lin, C-C; Chen, W-J","year":2013,"journal":"Journal of dairy science, 96(12), 7511-20","doi":"10.3168/jds.2013-7285","pmid":"24140317","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02255","title":"NTproBNP: an important biomarker in cardiac diseases.","authors":"Panagopoulou, Vasiliki; Deftereos, Spyridon; Kossyvakis, Charalampos; Raisakis, Konstantinos; Giannopoulos, Georgios; Bouras, Georgios; Pyrgakis, Vlasios; Cleman, Michael W","year":2013,"journal":"Current topics in medicinal chemistry, 13(2), 82-94","doi":null,"pmid":"23470072","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"NT-proBNP has established itself as a gold standard biomarker for heart failure with the following key characteristics:\n\n- A cutoff of 300 pg/mL provides 99% sensitivity, 60% specificity, and 98% negative predictive value for ruling out acute heart failure\n- NT-proBNP has a longer half-life and higher plasma concentration than BNP, making it easier to measure\n- It strongly predicts death in both acute and chronic heart failure\n- It predicts short- and long-term mortality in patients with suspected or confirmed unstable cardiovascular disease\n- Levels are influenced by sex (higher in women), obesity (lower in obese individuals), and age (higher in elderly)\n- It may also help estimate the onset timing of atrial fibrillation of unknown duration","whyItMatters":"Natriuretic peptides represent one of the most successful examples of peptide biology being translated into routine clinical practice. NT-proBNP testing is now standard worldwide for heart failure diagnosis and management. Understanding how these peptides work — produced under cardiac stress, cleared by specific organs, varying by age, sex, and body weight — is fundamental to interpreting test results correctly and making treatment decisions.","specificNumbers":"","methodology":"This is a comprehensive review article that synthesizes clinical research on natriuretic peptides, focusing on NT-proBNP's biology, measurement, diagnostic accuracy, and prognostic value across various cardiac conditions.","limitations":"This review is from 2013 and does not include more recent developments in natriuretic peptide research. NT-proBNP levels are affected by many non-cardiac conditions (renal dysfunction, sepsis, liver cirrhosis), which can complicate interpretation. The biomarker is less reliable in obese patients (who may have falsely low levels) and in the elderly (who may have elevated levels without heart failure). Single cutoff values do not work optimally across all patient populations."},{"rthcId":"RPEP-02256","title":"Vitamin D receptor activation, left ventricular hypertrophy and myocardial fibrosis.","authors":"Panizo, Sara; Barrio-Vázquez, Sara; Naves-Díaz, Manuel; Carrillo-López, Natalia; Rodríguez, Isabel; Fernández-Vázquez, Amalia; Valdivielso, Jose M; Thadhani, Ravi; Cannata-Andía, Jorge B","year":2013,"journal":"Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 28(11), 2735-44","doi":"10.1093/ndt/gft268","pmid":"24013683","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02257","title":"Simultaneous display of two large proteins on the head and tail of bacteriophage lambda.","authors":"Pavoni, Emiliano; Vaccaro, Paola; D'Alessio, Valeria; De Santis, Rita; Minenkova, Olga","year":2013,"journal":"BMC biotechnology, 13, 79","doi":"10.1186/1472-6750-13-79","pmid":"24073829","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02258","title":"Intranasal oxytocin blocks alcohol withdrawal in human subjects.","authors":"Pedersen, Cort A; Smedley, Kelly L; Leserman, Jane; Jarskog, Lars Fredrik; Rau, Shane W; Kampov-Polevoi, Alexei; Casey, Robin L; Fender, Trace; Garbutt, James C","year":2013,"journal":"Alcoholism, clinical and experimental research, 37(3), 484-9","doi":"10.1111/j.1530-0277.2012.01958.x","pmid":"23025690","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02259","title":"Potential anticarcinogenic peptides from bovine milk.","authors":"Pepe, Giacomo; Tenore, Gian Carlo; Mastrocinque, Raffaella; Stusio, Paola; Campiglia, Pietro","year":2013,"journal":"Journal of amino acids, 2013, 939804","doi":"10.1155/2013/939804","pmid":"23533710","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02260","title":"Transport across Caco-2 monolayers of peptides arising from in vitro digestion of bovine milk proteins.","authors":"Picariello, Gianluca; Iacomino, Giuseppe; Mamone, Gianfranco; Ferranti, Pasquale; Fierro, Olga; Gianfrani, Carmen; Di Luccia, Aldo; Addeo, Francesco","year":2013,"journal":"Food chemistry, 139(1-4), 203-12","doi":"10.1016/j.foodchem.2013.01.063","pmid":"23561097","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02261","title":"Gonadotropin-inhibitory hormone reduces sexual motivation but not lordosis behavior in female Syrian hamsters (Mesocricetus auratus).","authors":"Piekarski, David J; Zhao, Sheng; Jennings, Kimberly J; Iwasa, Takeshi; Legan, Sandra J; Mikkelsen, Jens D; Tsutsui, Kazuyoshi; Kriegsfeld, Lance J","year":2013,"journal":"Hormones and behavior, 64(3), 501-10","doi":"10.1016/j.yhbeh.2013.06.006","pmid":"23827890","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02262","title":"Delivery of analgesic peptides to the brain by nano-sized bolaamphiphilic vesicles made of monolayer membranes.","authors":"Popov, Mary; Abu Hammad, Ibrahim; Bachar, Tzach; Grinberg, Sarina; Linder, Charles; Stepensky, David; Heldman, Eliahu","year":2013,"journal":"European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 85(3 Pt A), 381-9","doi":"10.1016/j.ejpb.2013.06.005","pmid":"23791683","tags":[],"studyType":"animal study","evidenceStrength":"low","keyFinding":"Synthetic monolayer membrane vesicles called \"bolavesicles\" successfully delivered two analgesic peptides — kyotorphin and leu-enkephalin — across the blood-brain barrier in mice, producing efficient and prolonged pain relief. The best results came from mixed bolavesicle formulations (GLH-19/GLH-20) with chitosan. A key innovation was the controlled release mechanism: the vesicles contain acetylcholine-like head groups that are broken down by cholinesterase enzymes specifically abundant in the brain, triggering peptide release at the target site. Pretreatment with pyridostigmine (a cholinesterase inhibitor that doesn't cross the BBB) enhanced the analgesic effect, confirming that brain-specific enzyme activity drives the release.","whyItMatters":"The body produces its own pain-killing peptides (enkephalins, endorphins, kyotorphin), but they can't be used as drugs because they don't cross the blood-brain barrier and are quickly degraded in the bloodstream. If nanocarriers could deliver these natural analgesic peptides to the brain in sufficient quantities, they could provide pain relief through the body's own opioid system — potentially offering an alternative to synthetic opioids with their addiction risks. The brain-specific release mechanism is particularly elegant because it minimizes off-target effects.","specificNumbers":"2 analgesic peptides delivered (kyotorphin, leu-enkephalin) · Bolavesicles from GLH-19/GLH-20 · Chitosan enhancement · ChE-dependent brain release · Prolonged analgesic activity","methodology":"Researchers prepared cationic bolavesicles from synthetic bolaamphiphiles (GLH-19 and GLH-20) with and without chitosan, encapsulating the analgesic peptides kyotorphin and leu-enkephalin. Formulations were administered to ICR mice, and analgesic effects were measured in vivo. To confirm the brain-specific release mechanism, mice were pretreated with pyridostigmine (a BBB-impermeable cholinesterase inhibitor) before receiving the formulations.","limitations":"This is a mouse study — human BBB permeability and cholinesterase distribution may differ. The specific analgesic assays used and quantitative pain scores are not detailed in the abstract. Pharmacokinetic data (how much peptide actually reaches the brain) is not provided. Long-term safety of repeated bolavesicle administration is unknown. The manufacturing scalability and stability of the formulations are not addressed. The study is from 2013 and the technology may not have advanced to clinical development."},{"rthcId":"RPEP-02263","title":"A short history of parathyroid hormone, its biological role, and pathophysiology of hormone excess.","authors":"Potts, John T","year":2013,"journal":"Journal of clinical densitometry : the official journal of the International Society for Clinical Densitometry, 16(1), 4-7","doi":"10.1016/j.jocd.2012.11.002","pmid":"23374734","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02264","title":"Microbial symbionts accelerate wound healing via the neuropeptide hormone oxytocin.","authors":"Poutahidis, Theofilos; Kearney, Sean M; Levkovich, Tatiana; Qi, Peimin; Varian, Bernard J; Lakritz, Jessica R; Ibrahim, Yassin M; Chatzigiagkos, Antonis; Alm, Eric J; Erdman, Susan E","year":2013,"journal":"PloS one, 8(10), e78898","doi":"10.1371/journal.pone.0078898","pmid":"24205344","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02265","title":"Ghrelin: much more than a hunger hormone.","authors":"Pradhan, Geetali; Samson, Susan L; Sun, Yuxiang","year":2013,"journal":"Current opinion in clinical nutrition and metabolic care, 16(6), 619-24","doi":"10.1097/MCO.0b013e328365b9be","pmid":"24100676","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02266","title":"A heterodimer comprised of two bovine lactoferrin antimicrobial peptides exhibits powerful bactericidal activity against Burkholderia pseudomallei.","authors":"Puknun, Aekkalak; Bolscher, Jan G M; Nazmi, Kamran; Veerman, Enno C I; Tungpradabkul, Sumalee; Wongratanacheewin, Surasakdi; Kanthawong, Sakawrat; Taweechaisupapong, Suwimol","year":2013,"journal":"World journal of microbiology & biotechnology, 29(7), 1217-24","doi":"10.1007/s11274-013-1284-6","pmid":"23404819","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02267","title":"Acute and second-meal effects of peanuts on glycaemic response and appetite in obese women with high type 2 diabetes risk: a randomised cross-over clinical trial.","authors":"Reis, Caio E G; Ribeiro, Daniela N; Costa, Neuza M B; Bressan, Josefina; Alfenas, Rita C G; Mattes, Richard D","year":2013,"journal":"The British journal of nutrition, 109(11), 2015-23","doi":"10.1017/S0007114512004217","pmid":"23122211","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02268","title":"Mechanisms of synergism between antagonists of growth hormone-releasing hormone and antagonists of luteinizing hormone-releasing hormone in shrinking experimental benign prostatic hyperplasia.","authors":"Rick, Ferenc G; Schally, Andrew V; Block, Norman L; Abi-Chaker, Andrew; Krishan, Awtar; Szalontay, Luca","year":2013,"journal":"The Prostate, 73(8), 873-83","doi":"10.1002/pros.22633","pmid":"23280565","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02269","title":"Anorexigenic postprandial responses of PYY and GLP1 to slow ice cream consumption: preservation in obese adolescents, but not in obese adults.","authors":"Rigamonti, A E; Agosti, F; Compri, E; Giunta, M; Marazzi, N; Muller, E E; Cella, S G; Sartorio, A","year":2013,"journal":"European journal of endocrinology, 168(3), 429-36","doi":"10.1530/EJE-12-0867","pmid":"23239758","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Fast eating did not stimulate GLP-1 release in either age group, while slow eating increased circulating GLP-1 only in obese adolescents. PYY increased after both fast and slow eating in both groups, but slow eating was significantly more effective at stimulating PYY release in obese adolescents compared to adults.\n\nSlow eating evoked higher satiety only in obese adolescents, with reduced hunger at 210 minutes. Obese adults showed no significant differences in satiety or hunger between eating rates. Postprandial insulin and triglyceride responses were higher in obese adults than adolescents regardless of eating speed, reflecting greater metabolic dysregulation with age and prolonged obesity.","whyItMatters":"This study reveals that the body's natural appetite-suppressing peptide response to slow eating degrades with age and prolonged obesity. For obese teens, simply eating more slowly may boost the very same gut peptides (GLP-1 and PYY) that pharmaceutical drugs target. The loss of this response in adults suggests that early intervention for obesity may be critical before the gut's regulatory mechanisms become impaired.","specificNumbers":"","methodology":"Crossover study design where 18 obese adolescents and adults each consumed the same test meal on two sessions — in 5 minutes (fast) or 30 minutes (slow). Blood was drawn over 210 minutes to measure GLP-1, PYY, glucose, insulin, and triglycerides. Visual analog scales assessed subjective hunger and satiety at multiple time points.","limitations":"The sample size of 18 subjects is small, limiting statistical power and generalizability. Only one meal type (ice cream) was tested, which may not represent typical diets. The study compared adolescents and adults but could not separate the effects of age from duration of obesity. The crossover design is a strength, but the short-term nature doesn't show whether habitual slow eating produces lasting effects."},{"rthcId":"RPEP-02270","title":"The role of histamine in neurogenic inflammation.","authors":"Rosa, A C; Fantozzi, R","year":2013,"journal":"British journal of pharmacology, 170(1), 38-45","doi":"10.1111/bph.12266","pmid":"23734637","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02271","title":"Appetite regulation in overweight, sedentary men after different amounts of endurance exercise: a randomized controlled trial.","authors":"Rosenkilde, Mads; Reichkendler, Michala Holm; Auerbach, Pernille; Toräng, Signe; Gram, Anne Sofie; Ploug, Thorkil; Holst, Jens Juul; Sjödin, Anders; Stallknecht, Bente","year":2013,"journal":"Journal of applied physiology (Bethesda, Md. : 1985), 115(11), 1599-609","doi":"10.1152/japplphysiol.00680.2013","pmid":"24052035","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02272","title":"Discovery of cyclic sulfoxide hydroxyethylamines as potent and selective β-site APP-cleaving enzyme 1 (BACE1) inhibitors: structure based design and in vivo reduction of amyloid β-peptides.","authors":"Rueeger, Heinrich; Lueoend, Rainer; Machauer, Rainer; Veenstra, Siem Jacob; Jacobson, Laura Helen; Staufenbiel, Matthias; Desrayaud, Sandrine; Rondeau, Jean-Michel; Möbitz, Henrik; Neumann, Ulf","year":2013,"journal":"Bioorganic & medicinal chemistry letters, 23(19), 5300-6","doi":"10.1016/j.bmcl.2013.07.071","pmid":"23981898","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02273","title":"Effects of intraduodenal lipid and protein on gut motility and hormone release, glycemia, appetite, and energy intake in lean men.","authors":"Ryan, Amy T; Luscombe-Marsh, Natalie D; Saies, Alexander A; Little, Tanya J; Standfield, Scott; Horowitz, Michael; Feinle-Bisset, Christine","year":2013,"journal":"The American journal of clinical nutrition, 98(2), 300-11","doi":"10.3945/ajcn.113.061333","pmid":"23803895","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02274","title":"Neuropeptide Y and posttraumatic stress disorder.","authors":"Sah, R; Geracioti, T D","year":2013,"journal":"Molecular psychiatry, 18(6), 646-55","doi":"10.1038/mp.2012.101","pmid":"22801411","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review consolidates evidence from multiple lines of research pointing to NPY as a stress resilience factor:\n\n• Animal studies demonstrate that NPY promotes coping behaviors during stress, particularly in forebrain limbic and brainstem areas that regulate emotional responses.\n• Genetic, physiological, and clinical data in humans implicate NPY as a potential resilience-to-stress factor.\n• Reduced central nervous system NPY concentrations or function appear to be associated with PTSD.\n• Specific PTSD symptoms (avoidance, hyperarousal, fear conditioning, impaired extinction) map onto known functions of the NPY system in the brain.\n\nCollectively, the evidence suggests NPY deficiency may contribute to PTSD vulnerability rather than being merely a consequence of the disorder.","whyItMatters":"PTSD affects approximately 6-8% of the population at some point in their lives, and current treatments (SSRIs, psychotherapy) have limited efficacy. Understanding that a specific brain peptide may determine vulnerability to PTSD opens the door to entirely new treatment approaches — potentially boosting NPY levels or mimicking its effects to help people recover from trauma or even prevent PTSD in high-risk populations like military personnel and first responders.","specificNumbers":"","methodology":"This was a narrative review consolidating preclinical (primarily rodent) and clinical (human) studies on neuropeptide Y and stress-related disorders. The authors examined genetic studies, physiological measurements of NPY in humans, animal behavioral experiments, and clinical PTSD data to build an integrative picture of NPY's role in trauma resilience.","limitations":"Much of the evidence linking NPY to PTSD comes from animal models, which may not fully capture the complexity of human trauma responses. The review is narrative rather than systematic, so study selection may reflect author perspective. Establishing causation (does low NPY cause PTSD vulnerability, or does PTSD reduce NPY?) remains challenging. The review does not address whether NPY-based interventions have been tested in PTSD clinical trials."},{"rthcId":"RPEP-02275","title":"Growth hormone-releasing hormone-producing pancreatic neuroendocrine tumor in a multiple endocrine neoplasia type 1 family with an uncommon phenotype.","authors":"Sala, Elisa; Ferrante, Emanuele; Verrua, Elisa; Malchiodi, Elena; Mantovani, Giovanna; Filopanti, Marcello; Ferrero, Stefano; Pietrabissa, Andrea; Vanoli, Alessandro; La Rosa, Stefano; Zatelli, Maria C; Beck-Peccoz, Paolo; Verga, Uberta","year":2013,"journal":"European journal of gastroenterology & hepatology, 25(7), 858-62","doi":"10.1097/MEG.0b013e32835f433f","pmid":"23542451","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02276","title":"Natriuretic peptide-guided therapy in chronic heart failure: a meta-analysis of 2,686 patients in 12 randomized trials.","authors":"Savarese, Gianluigi; Trimarco, Bruno; Dellegrottaglie, Santo; Prastaro, Maria; Gambardella, Francesco; Rengo, Giuseppe; Leosco, Dario; Perrone-Filardi, Pasquale","year":2013,"journal":"PloS one, 8(3), e58287","doi":"10.1371/journal.pone.0058287","pmid":"23472172","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02277","title":"Semagacestat, a γ-secretase inhibitor, activates the growth hormone secretagogue (GHS-R1a) receptor.","authors":"Schellekens, Harriët; McNamara, Orla; Dinan, Timothy G; McCarthy, Justin V; McGlacken, Gerard P; Cryan, John F","year":2013,"journal":"The Journal of pharmacy and pharmacology, 65(4), 528-38","doi":"10.1111/jphp.12010","pmid":"23488781","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02278","title":"Transplantation of pancreatic islets to adrenal gland is promoted by agonists of growth-hormone-releasing hormone.","authors":"Schubert, Undine; Schmid, Janine; Lehmann, Susann; Zhang, Xian Y; Morawietz, Henning; Block, Norman L; Kanczkowski, Waldemar; Schally, Andrew V; Bornstein, Stefan R; Ludwig, Barbara","year":2013,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 110(6), 2288-93","doi":"10.1073/pnas.1221505110","pmid":"23345449","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02279","title":"Combination of GHRH antagonists and docetaxel shows experimental effectiveness for the treatment of triple-negative breast cancers.","authors":"Seitz, S; Rick, F G; Schally, A V; Treszl, A; Hohla, F; Szalontay, L; Zarandi, M; Ortmann, O; Engel, J B; Buchholz, S","year":2013,"journal":"Oncology reports, 30(1), 413-8","doi":"10.3892/or.2013.2435","pmid":"23624870","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In MDA-MB-231 triple-negative breast cancer xenografts in nude mice:\n- GHRH antagonist JMR-132 alone: 46% tumor growth inhibition\n- Docetaxel alone: 50% tumor growth inhibition\n- Combination: 71.6% tumor growth inhibition (p<0.001)\n\nIn vitro, both JMR-132 and docetaxel reduced cell viability dose-dependently, with the combination producing significantly greater inhibition than either agent alone. PCR array analysis of tumor tissue revealed that JMR-132 interacts with signal transduction pathways involved in proliferation, apoptosis, and angiogenesis, explaining its multi-faceted anti-tumor mechanism.","whyItMatters":"Triple-negative breast cancer affects about 15% of breast cancer patients and has the worst prognosis because it doesn't respond to hormonal or HER2-targeted therapies. Finding combination strategies that significantly improve on chemotherapy alone could meaningfully change outcomes for these patients.","specificNumbers":"","methodology":"GHRH receptor expression in MDA-MB-231 cells was confirmed by RT-PCR. In vitro cell viability assays tested JMR-132, docetaxel, and their combination. In vivo, nude mice bearing subcutaneous MDA-MB-231 xenografts received JMR-132 (10 µg/day s.c.) and/or docetaxel (10 mg/kg i.p. on days 1 and 5). A human cancer pathway array analyzing 84 genes was performed on tumor tissue to elucidate mechanism of action.","limitations":"This is a preclinical study using a single TNBC cell line in immunocompromised mice. Human tumors are more heterogeneous and exist within a functional immune system. The dosing schedule was short-term, and long-term efficacy and toxicity were not assessed. Only one GHRH antagonist and one chemotherapy agent were tested."},{"rthcId":"RPEP-02280","title":"Comparison of the diagnostic and prognostic values of B-type and atrial-type natriuretic peptides in acute heart failure.","authors":"Seronde, Marie-France; Gayat, Etienne; Logeart, Damien; Lassus, Johan; Laribi, Said; Boukef, Riadh; Sibellas, Franck; Launay, Jean-Marie; Manivet, Philippe; Sadoune, Malha; Nouira, Semir; Solal, Alain Cohen; Mebazaa, Alexandre","year":2013,"journal":"International journal of cardiology, 168(4), 3404-11","doi":"10.1016/j.ijcard.2013.04.164","pmid":"23684562","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02281","title":"Novel, biocompatible, and disease modifying VIP nanomedicine for rheumatoid arthritis.","authors":"Sethi, Varun; Rubinstein, Israel; Kuzmis, Antonina; Kastrissios, Helen; Artwohl, James; Onyuksel, Hayat","year":2013,"journal":"Molecular pharmaceutics, 10(2), 728-38","doi":"10.1021/mp300539f","pmid":"23211088","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02282","title":"Thymosin alpha-1-transformed Bifidobacterium promotes T cell proliferation and maturation in mice by oral administration.","authors":"Shao, Congwen; Tian, Guojun; Huang, Yuanjian; Liang, Wenying; Zheng, Hang; Wei, Jiannan; Wei, Cheng; Yang, Cuilan; Wang, Hong; Zeng, Weisen","year":2013,"journal":"International immunopharmacology, 15(3), 646-53","doi":"10.1016/j.intimp.2012.12.031","pmid":"23352493","tags":["thymosin","immune-peptides"],"studyType":"animal","evidenceStrength":"preliminary","keyFinding":"Researchers engineered Bifidobacterium longum bacteria to produce human thymosin alpha-1 (Tα1), then fed these bacteria to mice orally every other day for two weeks. Compared to control bacteria, the Tα1-producing bacteria significantly increased CD3+CD4+ and CD3+CD8+ T cells in the blood, spleen, and thymus, and boosted CD4+CD8+ cells in the thymus and spleen.\n\nThe immune-stimulating cytokines IFN-γ and IL-12 were significantly elevated in serum, while TNF-α and IL-4 were unchanged — indicating selective activation of the Th1 (cellular immunity) pathway. After three months of treatment, the mice showed thymic hyperplasia (enlarged thymus) and lymph node enlargement, confirming sustained immune organ growth from oral delivery.","whyItMatters":"Thymosin alpha-1 is an established immune-boosting peptide used clinically to treat immune deficiency and as an adjunct in hepatitis B and cancer therapy — but it must be given by injection. Converting it to an oral medication delivered by a probiotic bacterium could dramatically improve patient compliance and reduce side effects. This proof-of-concept in mice shows that a living bacterial delivery system can successfully produce and release a therapeutic peptide in the gut, where it stimulates systemic immune responses.","specificNumbers":"Oral dosing every other day for 2 weeks · significant increases in CD4+ and CD8+ T cells · IFN-γ and IL-12 elevated · TNF-α and IL-4 unchanged · thymic hyperplasia and lymph node enlargement at 3 months · 0.2% L-arabinose induction","methodology":"The researchers cloned the human thymosin alpha-1 gene into Bifidobacterium longum using an arabinose-inducible expression system. BALB/c mice received oral doses of the engineered bacteria (pre-induced with 0.2% L-arabinose) every other day for two weeks. Controls received bacteria transformed with an empty vector or normal saline. T cell populations were measured by flow cytometry in blood, spleen, and thymus. Serum cytokines (IFN-γ, IL-12, TNF-α, IL-4) were quantified. Long-term effects on thymus and lymph node morphology were assessed after three months.","limitations":"This is a mouse study with no human data. The long-term safety of oral genetically modified bacteria is not well characterized. The thymic hyperplasia and lymph node enlargement observed at three months could potentially be concerning if they represent immune over-stimulation. The study does not quantify how much Tα1 actually reaches systemic circulation, and the mechanism of absorption from the gut is not fully characterized. Regulatory hurdles for genetically modified organisms as drug delivery vehicles are substantial."},{"rthcId":"RPEP-02283","title":"Hydrogen exchange-mass spectrometry measures stapled peptide conformational dynamics and predicts pharmacokinetic properties.","authors":"Shi, Xiangguo Eric; Wales, Thomas E; Elkin, Carl; Kawahata, Noriyuki; Engen, John R; Annis, D Allen","year":2013,"journal":"Analytical chemistry, 85(23), 11185-8","doi":"10.1021/ac403173p","pmid":"24215480","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02284","title":"Keratinocytes express cytokines and nerve growth factor in response to neuropeptide activation of the ERK1/2 and JNK MAPK transcription pathways.","authors":"Shi, Xiaoyou; Wang, Liping; Clark, J David; Kingery, Wade S","year":2013,"journal":"Regulatory peptides, 186, 92-103","doi":"10.1016/j.regpep.2013.08.001","pmid":"23958840","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Both substance P (SP) and CGRP concentration-dependently stimulated keratinocyte proliferation and production of IL-1β, IL-6, TNF-α, and nerve growth factor (NGF). SP activated all three MAPK families (ERK1/2, JNK, p38) plus NFκB, while CGRP activated only ERK1/2 and p38.\n\nThe study revealed several novel findings: CGRP stimulates keratinocyte expression of both CGRP itself and its receptor complex (creating an autocrine amplification loop); SP and CGRP both stimulate IL-6 and TNF-α secretion (previously unknown); SP activates all three MAPK families plus NFκB in keratinocytes; and the inflammatory mediator production driven by both neuropeptides depends specifically on ERK1/2 and JNK activation, as inhibitors of these pathways reversed the effects.","whyItMatters":"Many chronic skin conditions — including eczema, psoriasis, rosacea, and neurogenic inflammation — involve excessive nerve-skin signaling that drives inflammation and pain. By identifying ERK1/2 and JNK as the specific pathways through which neuropeptides drive keratinocyte inflammation, this study points to concrete drug targets. The discovery of the autocrine amplification loop (neuropeptides causing cells to make more neuropeptides and receptors) also explains how localized nerve irritation can escalate into widespread skin inflammation.","specificNumbers":"","methodology":"The study used a keratinocyte cell line to perform receptor expression analysis, neuropeptide stimulation assays, proliferation measurements, cytokine/NGF expression and secretion quantification, and MAPK/NFκB signaling pathway activation studies. ERK1/2 and JNK inhibitors were used to confirm the signaling dependencies. Both substance P and CGRP were tested at varying concentrations to establish dose-response relationships.","limitations":"The study used a keratinocyte cell line rather than primary keratinocytes or intact skin, which may not fully replicate the complexity of in vivo neuropeptide-keratinocyte interactions. Rat-derived cells were used, and species differences in neuropeptide signaling may exist. The study did not test whether ERK1/2 or JNK inhibition would reduce inflammation in animal models of skin disease. The role of other cell types present in skin (immune cells, fibroblasts, endothelial cells) was not addressed."},{"rthcId":"RPEP-02285","title":"Effect of neuropeptide Y on food intake in bullfrog larvae.","authors":"Shimizu, Shunsuke; Azuma, Morio; Morimoto, Noriaki; Kikuyama, Sakae; Matsuda, Kouhei","year":2013,"journal":"Peptides, 46, 102-7","doi":"10.1016/j.peptides.2013.05.014","pmid":"23756158","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02286","title":"Cystatin C versus creatinine in determining risk based on kidney function.","authors":"Shlipak, Michael G; Matsushita, Kunihiro; Ärnlöv, Johan; Inker, Lesley A; Katz, Ronit; Polkinghorne, Kevan R; Rothenbacher, Dietrich; Sarnak, Mark J; Astor, Brad C; Coresh, Josef; Levey, Andrew S; Gansevoort, Ron T","year":2013,"journal":"The New England journal of medicine, 369(10), 932-43","doi":"10.1056/NEJMoa1214234","pmid":"24004120","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02287","title":"Reduced expression of pain mediators and pain sensitivity in amyloid precursor protein over-expressing CRND8 transgenic mice.","authors":"Shukla, M; Quirion, R; Ma, W","year":2013,"journal":"Neuroscience, 250, 92-101","doi":"10.1016/j.neuroscience.2013.06.064","pmid":"23850592","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02288","title":"Toxicity by NSAIDs. Counteraction by stable gastric pentadecapeptide BPC 157.","authors":"Sikiric, Predrag; Seiwerth, Sven; Rucman, Rudolf; Turkovic, Branko; Rokotov, Dinko Stancic; Brcic, Luka; Sever, Marko; Klicek, Robert; Radic, Bozo; Drmic, Domagoj; Ilic, Spomenko; Kolenc, Danijela; Aralica, Gorana; Safic, Hana; Suran, Jelena; Rak, Davor; Dzidic, Senka; Vrcic, Hrvoje; Sebecic, Bozidar","year":2013,"journal":"Current pharmaceutical design, 19(1), 76-83","doi":null,"pmid":"22950504","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02289","title":"Food restriction, ghrelin, its antagonist and obestatin control expression of ghrelin and its receptor in chicken hypothalamus and ovary.","authors":"Sirotkin, Alexander V; Pavlova, Silvia; Tena-Sempere, Manuel; Grossmann, Roland; Jiménez, Magdalena Romero; Rodriguez, Juan Manuel Castellano; Valenzuela, Francisco","year":2013,"journal":"Comparative biochemistry and physiology. Part A, Molecular & integrative physiology, 164(1), 141-53","doi":"10.1016/j.cbpa.2012.07.010","pmid":"22877785","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02290","title":"Opioid receptors and their ligands in the musculoskeletal system and relevance for pain control.","authors":"Spetea, Mariana","year":2013,"journal":"Current pharmaceutical design, 19(42), 7382-90","doi":null,"pmid":"23448480","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02291","title":"Individual differences in the effects of chronic stress on memory: behavioral and neurochemical correlates of resiliency.","authors":"Sweis, B M; Veverka, K K; Dhillon, E S; Urban, J H; Lucas, L R","year":2013,"journal":"Neuroscience, 246, 142-59","doi":"10.1016/j.neuroscience.2013.04.052","pmid":"23644054","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02292","title":"Long-term administration of intranasal oxytocin is a safe and promising therapy for early adolescent boys with autism spectrum disorders.","authors":"Tachibana, Masaya; Kagitani-Shimono, Kuriko; Mohri, Ikuko; Yamamoto, Tomoka; Sanefuji, Wakako; Nakamura, Ayumi; Oishi, Masako; Kimura, Tadashi; Onaka, Tatsushi; Ozono, Keiichi; Taniike, Masako","year":2013,"journal":"Journal of child and adolescent psychopharmacology, 23(2), 123-7","doi":"10.1089/cap.2012.0048","pmid":"23480321","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Six of eight participants showed improved scores on the communication and social interaction domains of the Autism Diagnostic Observation Schedule (ADOS-G). Caregivers of five participants reported positive effects, particularly in the quality of reciprocal communication.\n\nHowever, standardized behavioral measures (Child Behavior Checklist T-scores and Aberrant Behavior Checklist scores) did not reach statistical significance, though some subcategories showed mild improvement trends. Critically, all eight participants showed excellent compliance and zero side effects across the entire treatment period, with normal blood pressure, blood, and urine results throughout.","whyItMatters":"Most previous oxytocin-autism research used single doses in adults, leaving major questions about whether the treatment is safe for children over extended periods. This study provided the first evidence that long-term nasal oxytocin is safe in adolescents with autism — a critical prerequisite for designing the larger, longer clinical trials needed to determine whether oxytocin can meaningfully help young people with social communication difficulties.","specificNumbers":"","methodology":"This was a single-armed, open-label pilot study in eight male adolescents with ASD (ages 10-14, IQ range 20-101). Oxytocin was administered intranasally with stepwise dose increases every 2 months (8, 16, then 24 IU per dose). A 1-2 week placebo period was inserted before each dose step. Outcomes were measured using the ADOS-G, Child Behavior Checklist (CBCL), and Aberrant Behavior Checklist (ABC). Safety was monitored via blood pressure, blood tests, and urinalysis.","limitations":"This was a very small (n=8), open-label study with no control group, making it impossible to separate oxytocin's effects from placebo responses or natural development. The wide IQ range (20-101) adds heterogeneity. Behavioral rating scales did not reach statistical significance. The authors themselves acknowledge the results are too preliminary for definitive conclusions about efficacy."},{"rthcId":"RPEP-02293","title":"Peripheral substance P and neurokinin-1 receptors have a role in inflammatory and neuropathic orofacial pain models.","authors":"Teodoro, Fernanda C; Tronco Júnior, Marcos F; Zampronio, Aleksander R; Martini, Alessandra C; Rae, Giles A; Chichorro, Juliana G","year":2013,"journal":"Neuropeptides, 47(3), 199-206","doi":"10.1016/j.npep.2012.10.005","pmid":"23177733","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The study revealed a highly specific pattern for peripheral substance P signaling in orofacial pain:\n\n- Substance P (1 µg/50 µL) injected into the upper lip induced heat hyperalgesia but not cold hyperalgesia, mechanical hyperalgesia, or spontaneous pain behavior\n- The NK1 receptor antagonist SR140333B (3 mg/kg, which does not cross the blood-brain barrier) reduced substance P-induced heat hyperalgesia, carrageenan-induced heat hyperalgesia, and both phases of the formalin response by ~50%\n- SR140333B abolished heat hyperalgesia caused by infraorbital nerve constriction (trigeminal neuropathic pain model) but did not affect cold or mechanical hyperalgesia\n- SR140333B did not reduce carrageenan-induced cold hyperalgesia\n\nBecause the NK1 antagonist cannot cross the BBB and substance P was injected peripherally, these results specifically demonstrate peripheral (not central) substance P/NK1 signaling in facial heat pain.","whyItMatters":"Facial pain conditions — including trigeminal neuralgia, TMJ disorders, and dental pain — are among the most debilitating chronic pain conditions. Understanding that peripheral substance P specifically mediates heat pain (but not other pain types) in the face provides a more nuanced target for drug development. NK1 receptor antagonists that work peripherally could potentially treat facial pain without the side effects of drugs that enter the brain.","specificNumbers":"","methodology":"Wistar rats received peripheral injections of substance P at varying doses (0.1–100 µg/50 µL) into the upper lip and were assessed for spontaneous nociceptive behavior, heat hyperalgesia, cold hyperalgesia, and mechanical hyperalgesia. The NK1 receptor antagonist SR140333B (which does not cross the blood-brain barrier) was administered systemically at 3 mg/kg. Inflammatory pain was modeled with carrageenan injection and formalin testing in the orofacial region. Neuropathic pain was modeled by constriction of the infraorbital nerve (trigeminal neuropathy).","limitations":"The study was conducted in male Wistar rats, and pain processing may differ from humans, especially in the orofacial region. Only one NK1 antagonist was tested. The higher doses of substance P (up to 100 µg) failed to induce spontaneous pain, which may reflect dose-response complexities or species differences. The formalin test measures a chemically induced pain response that may not fully represent clinical inflammatory pain."},{"rthcId":"RPEP-02294","title":"Lateral septal infusions of the neuropeptide Y Y2 receptor agonist, NPY(13-36) differentially affect different defensive behaviors in male, Long Evans rats.","authors":"Trent, Natalie L; Menard, Janet L","year":2013,"journal":"Physiology & behavior, 110-111, 20-9","doi":"10.1016/j.physbeh.2012.12.011","pmid":"23274501","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Infusion of the NPY Y2 receptor agonist NPY(13-36) into the lateral septum significantly increased open-arm exploration in the elevated plus-maze test — a classic indicator of reduced anxiety. This anxiolytic effect was blocked by pre-treatment with the selective Y2 receptor antagonist BIIE 0246, confirming that Y2 receptors mediate the effect.\n\nHowever, the anxiolytic action was test-specific: NPY(13-36) reduced burying behavior in the shock-probe burying test but did not reduce anxiety in all threat-related behavioral measures. The Y2 antagonist blocked the plus-maze effect but not the shock-probe effect, suggesting that the anxiolytic actions of lateral septal NPY(13-36) involve Y2-dependent and Y2-independent mechanisms depending on the type of threat.","whyItMatters":"Anxiety disorders affect millions of people, and current medications like benzodiazepines and SSRIs have significant limitations. Understanding how neuropeptide Y — a naturally occurring brain peptide — regulates anxiety through specific receptor subtypes and brain regions could lead to more targeted anti-anxiety treatments with fewer side effects. The finding that Y2 receptors modulate specific types of anxiety suggests that peptide-based therapies could be designed to address particular anxiety subtypes.","specificNumbers":"","methodology":"In Experiment 1, male Long Evans rats received infusions of the NPY Y2 agonist NPY(13-36) directly into the lateral septum and were tested across a battery of anxiety models including the elevated plus-maze, shock-probe burying test, and other defensive behavior paradigms. In Experiment 2, rats were pre-infused with the highly selective Y2 antagonist BIIE 0246 before NPY(13-36) to verify Y2 receptor involvement. Behavioral outcomes included open-arm exploration time, burying duration, and other anxiety-related measures.","limitations":"This is an animal study using direct brain injection — a method not applicable to human treatment. The lateral septum infusion targets a very specific brain region, and the results may not reflect what happens with systemic NPY administration. Only male rats were studied, so sex differences in NPY-mediated anxiety regulation were not assessed. The different behavioral tests used may involve different forms of anxiety (exploratory vs. acute threat), making direct comparisons complex."},{"rthcId":"RPEP-02295","title":"The human cathelicidin LL-37 inhibits influenza A viruses through a mechanism distinct from that of surfactant protein D or defensins.","authors":"Tripathi, Shweta; Tecle, Tesfaldet; Verma, Anamika; Crouch, Erika; White, Mitchell; Hartshorn, Kevan L","year":2013,"journal":"The Journal of general virology, 94(Pt 1), 40-49","doi":"10.1099/vir.0.045013-0","pmid":"23052388","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02296","title":"High protein intake stimulates postprandial GLP1 and PYY release.","authors":"van der Klaauw, Agatha A; Keogh, Julia M; Henning, Elana; Trowse, Victoria M; Dhillo, Waljit S; Ghatei, Mohammad A; Farooqi, I Sadaf","year":2013,"journal":"Obesity (Silver Spring, Md.), 21(8), 1602-7","doi":"10.1002/oby.20154","pmid":"23666746","tags":[],"studyType":"rct","evidenceStrength":"low-moderate","keyFinding":"High-protein breakfasts significantly increased circulating levels of the satiety peptides GLP-1 and PYY compared to high-fat and high-carbohydrate breakfasts. PYY levels were highest after the protein meal (p=0.005), and GLP-1 was elevated from 120 minutes onward (p=0.041). However, these hormonal differences did not translate into reduced food intake at a subsequent meal — participants ate roughly the same amount regardless of breakfast composition (~1,023 kcal after protein vs. ~1,158 kcal after carbohydrate).\n\nGhrelin, the hunger hormone, decreased equally after all three breakfast types.","whyItMatters":"This study reveals an important disconnect between gut hormone responses and actual eating behavior. While high-protein meals boost the same satiety peptides that drugs like semaglutide and liraglutide target (GLP-1), the natural hormonal increase from food alone wasn't enough to reduce subsequent calorie intake — helping explain why pharmacological GLP-1 levels far exceeding natural responses may be needed for appetite suppression.","specificNumbers":"n=8 · 60% energy from protein/fat/carb · PYY highest after protein (p=0.005) · GLP-1 highest after protein (p=0.041) · Ad lib intake: ~1,023 vs ~1,016 vs ~1,158 kcal","methodology":"Randomized three-way crossover study in 8 healthy volunteers. Each participant received three different breakfasts on separate days, each providing 20% of daily energy needs with 60% of calories from either protein, fat, or carbohydrate. Meals were matched for volume, calories, and appearance. Blood was drawn every 30 minutes for 4 hours to measure gut hormones (GLP-1, PYY, ghrelin). Food intake was measured at a subsequent ad libitum meal.","limitations":"Very small sample size (8 participants) limits statistical power and generalizability. The study measured only one subsequent meal, not 24-hour intake. Participants were healthy volunteers, so results may differ in people with obesity or metabolic disorders. The crossover design is a strength but the small n remains a major limitation."},{"rthcId":"RPEP-02297","title":"Intranasal administration of oxytocin: behavioral and clinical effects, a review.","authors":"Veening, Jan G; Olivier, Berend","year":2013,"journal":"Neuroscience and biobehavioral reviews, 37(8), 1445-65","doi":"10.1016/j.neubiorev.2013.04.012","pmid":"23648680","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02298","title":"Blood pressure-lowering effects of GLP-1 receptor agonists exenatide and liraglutide: a meta-analysis of clinical trials.","authors":"Wang, B; Zhong, J; Lin, H; Zhao, Z; Yan, Z; He, H; Ni, Y; Liu, D; Zhu, Z","year":2013,"journal":"Diabetes, obesity & metabolism, 15(8), 737-49","doi":"10.1111/dom.12085","pmid":"23433305","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02299","title":"Isolation and characterization of collagen and antioxidant collagen peptides from scales of croceine croaker (Pseudosciaena crocea).","authors":"Wang, Bin; Wang, Yu-Mei; Chi, Chang-Feng; Luo, Hong-Yu; Deng, Shang-Gui; Ma, Jian-Yin","year":2013,"journal":"Marine drugs, 11(11), 4641-61","doi":"10.3390/md11114641","pmid":"24284428","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02300","title":"Increased postprandial energy expenditure may explain superior long term weight loss after Roux-en-Y gastric bypass compared to vertical banded gastroplasty.","authors":"Werling, Malin; Olbers, Torsten; Fändriks, Lars; Bueter, Marco; Lönroth, Hans; Stenlöf, Kaj; le Roux, Carel W","year":2013,"journal":"PloS one, 8(4), e60280","doi":"10.1371/journal.pone.0060280","pmid":"23573244","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Nine years after surgery, gastric bypass patients had significantly higher postprandial energy expenditure (p=0.018) and total 24-hour energy expenditure (p=0.048) compared to vertical banded gastroplasty (VBG) patients, despite similar body composition and food intake. Gastric bypass also produced significantly higher postprandial levels of the gut peptide hormones PYY and GLP-1 (both p<0.001). These exaggerated peptide responses may drive the increased calorie burning that explains superior long-term weight loss maintenance.","whyItMatters":"Understanding why gastric bypass produces better long-term weight loss than restrictive surgery like VBG is key to developing non-surgical obesity treatments. This study shows the advantage persists for at least 9 years and is linked to elevated gut peptide hormone responses — the same peptides (GLP-1, PYY) targeted by modern weight-loss drugs like semaglutide.","specificNumbers":"n=14 · 9 years post-surgery · higher postprandial EE (p=0.018) · higher 24h EE (p=0.048) · PYY and GLP-1 both p<0.001 · similar body composition and food intake","methodology":"Fourteen women from a randomized clinical trial (7 gastric bypass, 7 VBG) were assessed 9 years postoperatively at weight stability. Energy expenditure was measured via 24-hour indirect calorimetry in a respiratory chamber, with focus on postprandial and sleep periods. Body composition and calorie intake were assessed. Postprandial blood samples measured PYY and GLP-1 gut peptide hormone responses.","limitations":"Very small sample size (n=14, 7 per group). Only female participants. Single time-point assessment at 9 years — no longitudinal tracking of when the peptide differences emerged. Cannot establish causality between elevated GLP-1/PYY and increased energy expenditure. The groups were from a randomized trial, which is a strength, but the small numbers limit statistical power."},{"rthcId":"RPEP-02301","title":"The electrical response of bilayers to the bee venom toxin melittin: evidence for transient bilayer permeabilization.","authors":"Wiedman, Gregory; Herman, Katherine; Searson, Peter; Wimley, William C; Hristova, Kalina","year":2013,"journal":"Biochimica et biophysica acta, 1828(5), 1357-64","doi":"10.1016/j.bbamem.2013.01.021","pmid":"23384418","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02302","title":"Corticotropin-releasing factor 1 receptor antagonists: a patent review.","authors":"Williams, John P","year":2013,"journal":"Expert opinion on therapeutic patents, 23(8), 1057-68","doi":"10.1517/13543776.2013.795545","pmid":"23642023","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02303","title":"Antiviral mechanisms of human defensins.","authors":"Wilson, Sarah S; Wiens, Mayim E; Smith, Jason G","year":2013,"journal":"Journal of molecular biology, 425(24), 4965-80","doi":"10.1016/j.jmb.2013.09.038","pmid":"24095897","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02304","title":"The efficacy of thymosin alpha 1 for severe sepsis (ETASS): a multicenter, single-blind, randomized and controlled trial.","authors":"Wu, Jianfeng; Zhou, Lixin; Liu, Jiyun; Ma, Gang; Kou, Qiuye; He, Zhijie; Chen, Juan; Ou-Yang, Bin; Chen, Minying; Li, Yinan; Wu, Xiaoqin; Gu, Baochun; Chen, Lei; Zou, Zijun; Qiang, Xinhua; Chen, Yuanyuan; Lin, Aihua; Zhang, Guanrong; Guan, Xiangdong","year":2013,"journal":"Critical care (London, England), 17(1), R8","doi":"10.1186/cc11932","pmid":"23327199","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02305","title":"Construction, expression, and characterization of thymosin alpha 1 tandem repeats in Escherichia coli.","authors":"Xue, Xiao-Chang; Yan, Zhen; Li, Wei-Na; Li, Meng; Qin, Xin; Zhang, Cun; Hao, Qiang; Wang, Zeng-Lu; Zhao, Ning; Zhang, Wei; Zhang, Ying-Qi","year":2013,"journal":"BioMed research international, 2013, 720285","doi":"10.1155/2013/720285","pmid":"23555093","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02306","title":"Treatment of the chronic itch of atopic dermatitis using standard drugs and kampo medicines.","authors":"Yamashita, Hirotaka; Tanaka, Hiroyuki; Inagaki, Naoki","year":2013,"journal":"Biological & pharmaceutical bulletin, 36(8), 1253-7","doi":null,"pmid":"23902969","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02307","title":"Role of nociceptors/neuropeptides in the pathogenesis of visceral hypersensitivity of nonerosive reflux disease.","authors":"Yoshida, Norimasa; Kuroda, Masaaki; Suzuki, Takahiro; Kamada, Kazuhiro; Uchiyama, Kazuhiko; Handa, Osamu; Takagi, Tomohisa; Yoshikawa, Toshikazu; Kuramoto, Hirofumi","year":2013,"journal":"Digestive diseases and sciences, 58(8), 2237-43","doi":"10.1007/s10620-012-2337-7","pmid":"22899239","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02308","title":"Angiotensin III: a physiological relevant peptide of the renin angiotensin system.","authors":"Yugandhar, Vudhya G; Clark, Michelle A","year":2013,"journal":"Peptides, 46, 26-32","doi":"10.1016/j.peptides.2013.04.014","pmid":"23692861","tags":["peptide-hormones"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Angiotensin III (Ang III), long considered a minor degradation product of angiotensin II, actually produces physiologically relevant effects comparable to Ang II. The review establishes that Ang III is a biologically active peptide in its own right within the renin-angiotensin system (RAS), with its own spectrum of effects on blood pressure, blood volume, sodium handling, thirst, and vasopressin release.\n\nThe RAS contains multiple active peptides — angiotensinogen, Ang II, Ang III, Ang IV, and Ang-(1-7) — each with distinct physiological roles. While research has overwhelmingly focused on Ang II, emerging data shows Ang III may be equally important in driving the pathological effects seen in heart failure, hypertension, heart attack, and diabetic kidney disease.","whyItMatters":"The renin-angiotensin system is one of the most important drug targets in medicine — ACE inhibitors and ARBs are among the most widely prescribed medications. Yet most research has focused almost exclusively on angiotensin II. Recognizing Ang III as a physiologically relevant peptide opens new therapeutic possibilities and may explain why some patients don't respond fully to current RAAS-targeting drugs.","specificNumbers":"Review covers: AGT, Ang II, Ang III, Ang IV, Ang-(1-7) · Diseases: heart failure, hypertension, MI, diabetic nephropathy · Multiple receptor types and signal transduction mechanisms","methodology":"This is a narrative review synthesizing published research on angiotensin III's physiological effects across multiple organ systems. The authors compiled evidence from animal studies, cell-based experiments, and clinical observations to build a comprehensive picture of Ang III's role within the RAS.","limitations":"As a narrative review, it does not follow systematic review methodology and may not capture all available evidence. Much of the Ang III data comes from animal studies, and the relative contribution of Ang III versus Ang II in human disease is still being defined. The review does not provide quantitative comparisons of potency between the angiotensin peptides."},{"rthcId":"RPEP-02309","title":"Attenuation of systemic morphine-induced analgesia by central administration of ghrelin and related peptides in mice.","authors":"Zeng, Ping; Chen, Jia-Xiang; Yang, Bei; Zhi, Xing; Guo, Fa-Xian; Sun, Meng-Li; Wang, Jing-Lei; Wei, Jie","year":2013,"journal":"Peptides, 50, 42-9","doi":"10.1016/j.peptides.2013.09.017","pmid":"24113541","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Intracerebroventricular injection of ghrelin at doses of 0.1 to 100 nmol/L inhibited the pain-relieving effect of systemic morphine (6 mg/kg) in the tail withdrawal test in mice. The GHS-R1a receptor agonists GHRP-6 and GHRP-2 similarly reduced morphine analgesia.\n\nCritically, pretreatment with the selective GHS-R1a antagonist [d-Lys(3)]-GHRP-6 (100 nmol/L) did not block the anti-opioid effects, demonstrating that ghrelin's interference with morphine pain relief occurs through a receptor mechanism independent of GHS-R1a. This points to an unidentified receptor or signaling pathway mediating the ghrelin-opioid interaction in the brain.","whyItMatters":"Understanding how different peptide systems in the brain interact with opioid pain pathways could lead to better pain management strategies and help explain why opioids work differently in different people. The discovery that ghrelin reduces morphine effectiveness through an unknown receptor also opens a new area of pharmacological research that could eventually yield novel targets for pain treatment or opioid optimization.","specificNumbers":"","methodology":"Male mice received ghrelin, GHRP-6, or GHRP-2 via intracerebroventricular (brain) injection, followed by systemic (intraperitoneal) morphine at 6 mg/kg. Pain sensitivity was measured using the tail withdrawal test. To determine receptor involvement, some mice were pretreated with the GHS-R1a antagonist [d-Lys(3)]-GHRP-6 before receiving ghrelin and morphine.","limitations":"This is a mouse study using direct brain injection, which is far from how either ghrelin or morphine is used clinically. The specific receptor or mechanism responsible for ghrelin's anti-opioid effect was not identified. Only one pain test (tail withdrawal) was used, so results may not generalize to other pain types. Dose-response relationships and potential differences between acute and chronic morphine exposure were not fully explored."},{"rthcId":"RPEP-02310","title":"Compatibility of olfactory ensheathing cells with functionalized self-assembling peptide scaffold in vitro.","authors":"Zhang, Ling-ling; Huang, Lin-hong; Zhang, Zhen-xing; Hao, Ding-jun; He, Bao-rong","year":2013,"journal":"Chinese medical journal, 126(20), 3891-6","doi":null,"pmid":"24157152","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02311","title":"Chemical synthesis of proteins using peptide hydrazides as thioester surrogates.","authors":"Zheng, Ji-Shen; Tang, Shan; Qi, Yun-Kun; Wang, Zhi-Peng; Liu, Lei","year":2013,"journal":"Nature protocols, 8(12), 2483-95","doi":"10.1038/nprot.2013.152","pmid":"24232250","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02312","title":"Anti-tumor effects of peptide analogs targeting neuropeptide hormone receptors on mouse pheochromocytoma cells.","authors":"Ziegler, C G; Ullrich, M; Schally, A V; Bergmann, R; Pietzsch, J; Gebauer, L; Gondek, K; Qin, N; Pacak, K; Ehrhart-Bornstein, M; Eisenhofer, G; Bornstein, S R","year":2013,"journal":"Molecular and cellular endocrinology, 371(1-2), 189-94","doi":"10.1016/j.mce.2012.12.011","pmid":"23267837","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02313","title":"Ghrelin in obesity, physiological and pharmacological considerations.","authors":"Álvarez-Castro, Paula; Pena, Lara; Cordido, Fernando","year":2013,"journal":"Mini reviews in medicinal chemistry, 13(4), 541-52","doi":null,"pmid":"22931534","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02314","title":"Gutierrez Rodrigues 2014 Flow Fish Vs Qpcr","authors":"","year":2014,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02315","title":"Katan 2014 Copeptin Stress Biomarker","authors":"","year":2014,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02316","title":"Mahler 2014 Ox1r Antagonism Cocaine Seeking","authors":"","year":2014,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02317","title":"The role of gastrointestinal hormones in the pathogenesis of obesity and type 2 diabetes.","authors":"Adamska, Edyta; Ostrowska, Lucyna; Górska, Maria; Krętowski, Adam","year":2014,"journal":"Przeglad gastroenterologiczny, 9(2), 69-76","doi":"10.5114/pg.2014.42498","pmid":"25061485","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02318","title":"GLP-1 receptor agonist-induced polyarthritis: a case report.","authors":"Ambrosio, Maria Luisa; Monami, Matteo; Sati, Lavinia; Marchionni, Niccolò; Di Bari, Mauro; Mannucci, Edoardo","year":2014,"journal":"Acta diabetologica, 51(4), 673-4","doi":"10.1007/s00592-013-0525-3","pmid":"24158775","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02319","title":"Intranasal oxytocin in the treatment of autism spectrum disorders: a review of literature and early safety and efficacy data in youth.","authors":"Anagnostou, Evdokia; Soorya, Latha; Brian, Jessica; Dupuis, Annie; Mankad, Deepali; Smile, Sharon; Jacob, Suma","year":2014,"journal":"Brain research, 1580, 188-98","doi":"10.1016/j.brainres.2014.01.049","pmid":"24508578","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02320","title":"Bovine and human lactoferricin peptides: chimeras and new cyclic analogs.","authors":"Arias, Mauricio; McDonald, Lindsey J; Haney, Evan F; Nazmi, Kamran; Bolscher, Jan G M; Vogel, Hans J","year":2014,"journal":"Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine, 27(5), 935-48","doi":"10.1007/s10534-014-9753-4","pmid":"24916114","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02321","title":"Oxytocin: its mechanism of action and receptor signalling in the myometrium.","authors":"Arrowsmith, S; Wray, S","year":2014,"journal":"Journal of neuroendocrinology, 26(6), 356-69","doi":"10.1111/jne.12154","pmid":"24888645","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02322","title":"Neuroendocrine control of satiation.","authors":"Asarian, Lori; Bächler, Thomas","year":2014,"journal":"Hormone molecular biology and clinical investigation, 19(3), 163-92","doi":"10.1515/hmbci-2014-0010","pmid":"25390024","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02323","title":"Vagal afferents are not necessary for the satiety effect of the gut lipid messenger oleoylethanolamide.","authors":"Azari, Elnaz Karimian; Ramachandran, Deepti; Weibel, Sandra; Arnold, Myrtha; Romano, Adele; Gaetani, Silvana; Langhans, Wolfgang; Mansouri, Abdelhak","year":2014,"journal":"American journal of physiology. Regulatory, integrative and comparative physiology, 307(2), R167-78","doi":null,"pmid":"24829501","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02324","title":"The role of oxytocin and vasopressin in emotional and social behaviors.","authors":"Bachner-Melman, Rachel; Ebstein, Richard P","year":2014,"journal":"Handbook of clinical neurology, 124, 53-68","doi":"10.1016/B978-0-444-59602-4.00004-6","pmid":"25248579","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02325","title":"Fourier transform infrared spectroscopy of peptides.","authors":"Bakshi, Kunal; Liyanage, Mangala R; Volkin, David B; Middaugh, C Russell","year":2014,"journal":"Methods in molecular biology (Clifton, N.J.), 1088, 255-69","doi":"10.1007/978-1-62703-673-3_18","pmid":"24146410","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02326","title":"Long-term exposure to intranasal oxytocin in a mouse autism model.","authors":"Bales, K L; Solomon, M; Jacob, S; Crawley, J N; Silverman, J L; Larke, R H; Sahagun, E; Puhger, K R; Pride, M C; Mendoza, S P","year":2014,"journal":"Translational psychiatry, 4(11), e480","doi":"10.1038/tp.2014.117","pmid":"25386957","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02327","title":"Interplay between RAS and opioids: opening the Pandora of complexities.","authors":"Bali, Anjana; Randhawa, Puneet Kaur; Jaggi, Amteshwar Singh","year":2014,"journal":"Neuropeptides, 48(4), 249-56","doi":"10.1016/j.npep.2014.05.002","pmid":"24877897","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02328","title":"Recommendations for the definition of clinical responder in insulin preservation studies.","authors":"Beam, Craig A; Gitelman, Stephen E; Palmer, Jerry P","year":2014,"journal":"Diabetes, 63(9), 3120-7","doi":"10.2337/db14-0095","pmid":"24722251","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02329","title":"Prospective, randomized, controlled, proof-of-concept study of the Ghrelin mimetic ipamorelin for the management of postoperative ileus in bowel resection patients.","authors":"Beck, David E; Sweeney, W Brian; McCarter, Martin D","year":2014,"journal":"International journal of colorectal disease, 29(12), 1527-34","doi":"10.1007/s00384-014-2030-8","pmid":"25331030","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02330","title":"Differential effects of intranasal oxytocin on sexual experiences and partner interactions in couples.","authors":"Behnia, Behnoush; Heinrichs, Markus; Bergmann, Wiebke; Jung, Stefanie; Germann, Janine; Schedlowski, Manfred; Hartmann, Uwe; Kruger, Tillmann H C","year":2014,"journal":"Hormones and behavior, 65(3), 308-18","doi":"10.1016/j.yhbeh.2014.01.009","pmid":"24503174","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02331","title":"Sustained neurochemical plasticity in central terminals of mouse DRG neurons following colitis.","authors":"Benson, Jessica R; Xu, Jiameng; Moynes, Derek M; Lapointe, Tamia K; Altier, Christophe; Vanner, Stephen J; Lomax, Alan E","year":2014,"journal":"Cell and tissue research, 356(2), 309-17","doi":"10.1007/s00441-014-1832-x","pmid":"24715114","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02332","title":"Interaction of stress, corticotropin-releasing factor, arginine vasopressin and behaviour.","authors":"Beurel, Eléonore; Nemeroff, Charles B","year":2014,"journal":"Current topics in behavioral neurosciences, 18, 67-80","doi":"10.1007/7854_2014_306","pmid":"24659554","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02333","title":"NK1 receptor antagonists as a new treatment for corneal neovascularization.","authors":"Bignami, Fabio; Giacomini, Chiara; Lorusso, Anna; Aramini, Andrea; Rama, Paolo; Ferrari, Giulio","year":2014,"journal":"Investigative ophthalmology & visual science, 55(10), 6783-94","doi":"10.1167/iovs.14-14553","pmid":"25228541","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Substance P levels increased in injured corneas in both the alkali burn and suture models. The NK1R antagonist Lanepitant, applied topically as eye drops, was nontoxic and reduced both blood vessel (hemangiogenesis) and lymphatic vessel (lymphangiogenesis) growth, corneal SP levels, and inflammatory cell (leukocyte) infiltration within 4 days in the alkali burn model.\n\nSubconjunctival injection of Lanepitant was effective in the suture model (where topical drops were insufficient), reducing lymphatic vessels, leukocyte infiltration, and SP levels after 10 days. In the alkali burn model, subconjunctival Lanepitant additionally reduced corneal perforation rates, opacity, and improved tear secretion. Befetupitant also showed efficacy but its vehicle (DMSO) was toxic to the eye surface.","whyItMatters":"Corneal neovascularization is a leading cause of vision loss worldwide, occurring after infections, chemical burns, contact lens complications, and transplant rejection. Current treatments (steroids, anti-VEGF agents) have significant limitations. Targeting Substance P through NK1R antagonists represents a completely different approach — addressing the neurogenic inflammation that drives vessel growth rather than blocking the growth factors directly. Since Lanepitant was already developed for other indications, repurposing it as an eye drop could accelerate clinical translation.","specificNumbers":"","methodology":"Researchers used two mouse models of corneal neovascularization (alkali burn and suture) in C57BL/6 mice. They tested Lanepitant and Befetupitant at different concentrations via topical eye drops or subconjunctival injection. Outcomes included clinical examination, Substance P levels, corneal neovascularization index, and leukocyte infiltration measurements.","limitations":"This is a mouse study, and corneal biology differs between mice and humans. The topical formulation was ineffective in the suture model (requiring injection), which may limit practical application. Specific quantitative outcome data (percentage reductions, p-values for each comparison) are partially described but not fully detailed in the abstract. Befetupitant's vehicle toxicity prevented complete evaluation. Long-term safety and efficacy of repeated NK1R antagonist use on the eye surface were not assessed."},{"rthcId":"RPEP-02334","title":"Endogenous opiates and behavior: 2013.","authors":"Bodnar, Richard J","year":2014,"journal":"Peptides, 62, 67-136","doi":"10.1016/j.peptides.2014.09.013","pmid":"25263178","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02335","title":"Smoking is associated with reduced leptin and neuropeptide Y levels and higher pain experience in patients with fibromyalgia.","authors":"Bokarewa, Maria I; Erlandsson, Malin C; Bjersing, Jan; Dehlin, Mats; Mannerkorpi, Kaisa","year":2014,"journal":"Mediators of inflammation, 2014, 627041","doi":"10.1155/2014/627041","pmid":"25197167","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 62 women with fibromyalgia, current smokers (n=18) had significantly lower leptin levels than ex-smokers (n=25, P=0.002). Normally, smoking stimulates neuropeptide Y (NPY) production through nicotinic receptors, but this expected NPY increase was absent in fibromyalgia patients. Without that compensatory NPY response, smokers with fibromyalgia experienced worse outcomes: higher pain scores on VAS (P=0.04), more tender points (P=0.03), and lower pain thresholds (P=0.01). NPY levels directly correlated with pain threshold (rho=0.414) and inversely correlated with tender point counts (rho=-0.375). The findings suggest that a broken leptin-NPY feedback loop may be a key mechanism underlying chronic pain in fibromyalgia.","whyItMatters":"Fibromyalgia's pain mechanisms remain poorly understood, which makes effective treatment difficult. This study identifies a specific peptide imbalance — the failure of neuropeptide Y to rise in response to low leptin — that may help explain why some fibromyalgia patients experience more severe pain. It also shows that smoking, which many patients may use as self-medication, actually worsens pain outcomes in this population through peptide dysregulation.","specificNumbers":"n=62 women · 18 current smokers · 25 ex-smokers · Leptin lower in smokers P=0.002 · VAS-pain higher P=0.04 · Tender points higher P=0.03 · Pain threshold lower P=0.01 · NPY-pain threshold rho=0.414","methodology":"Cross-sectional study of 62 women with fibromyalgia. Pain was assessed using a visual analogue scale (VAS), tender point counts, and pressure pain thresholds. Neuroendocrine markers (NPY, substance P) and adipokines (leptin, IGF-1, resistin, visfatin, adiponectin) were measured in blood and cerebrospinal fluid. Patients were grouped by smoking status: current smokers, ex-smokers, and never-smokers.","limitations":"Small sample of 62 women, limiting statistical power for subgroup analyses. Cross-sectional design cannot establish causation — it's unclear whether peptide dysregulation causes worse pain or results from it. All-female cohort limits generalizability to men with fibromyalgia. Self-reported smoking status may be unreliable."},{"rthcId":"RPEP-02336","title":"Counterregulation of insulin by leptin as key component of autonomic regulation of body weight.","authors":"Borer, Katarina T","year":2014,"journal":"World journal of diabetes, 5(5), 606-29","doi":"10.4239/wjd.v5.i5.606","pmid":"25317239","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The paper proposes a five-component model of body weight regulation centered on the counterregulation of insulin by leptin. Key components include: (1) the autonomic nervous system and suprachiasmatic clock coordinating energy intake and expenditure within a circadian framework; (2) interaction with brain reward circuits involving dopamine, ghrelin, melanin-concentrating hormone, and orexin-hypocretin peptides driving feeding and locomotion; (3) leptin counteracting insulin through multiple mechanisms — potentiating CCK-mediated satiation, inhibiting insulin secretion, opposing insulin's lipogenic effects with lipolytic action, and modulating insulin sensitivity; and (4) leptin's role in inhibiting bone mineral accrual, suggesting it helps maintain stability of skeletal, lean, and adipose tissue masses.","whyItMatters":"Understanding how peptide hormones like leptin, ghrelin, and insulin interact to regulate body weight is fundamental to developing better obesity and metabolic treatments. This model provides a framework for understanding why weight loss triggers hormonal changes that promote weight regain (reduced leptin increases insulin sensitivity and anabolic drive), and why obesity creates a different hormonal landscape (elevated leptin suppresses insulin's fat-storage effects).","specificNumbers":"","methodology":"This is a narrative review and theoretical synthesis. The author re-examined existing research on autonomic regulation, circadian biology, reward circuits, and peptide hormone signaling to formulate a new integrated model of body weight control. No new experimental data were generated.","limitations":"As a narrative review proposing a theoretical model, this paper does not present new experimental data or systematic evidence synthesis. The model is the author's integration of diverse research areas and has not been directly tested as a unified framework. Some proposed interactions may be oversimplified given the complexity of metabolic regulation."},{"rthcId":"RPEP-02337","title":"Hypophysiotropic gonadotropin-releasing hormone projections are exposed to dense plexuses of kisspeptin, neurokinin B and substance p immunoreactive fibers in the human: a study on tissues from postmenopausal women.","authors":"Borsay, Beáta Á; Skrapits, Katalin; Herczeg, László; Ciofi, Philippe; Bloom, Stephen R; Ghatei, Mohammad A; Dhillo, Waljit S; Liposits, Zsolt; Hrabovszky, Erik","year":2014,"journal":"Neuroendocrinology, 100(2-3), 141-52","doi":"10.1159/000368362","pmid":"25247878","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Immunohistochemistry of human hypothalamic tissue revealed:\n\n- Dense plexuses of kisspeptin (KP), neurokinin B (NKB), and substance P (SP) immunoreactive fibers in the postinfundibular eminence and infundibular stalk\n- These neuropeptide fiber networks innervated the portal capillary network and formed descending tracts to the neurohypophysis\n- KP, NKB, and SP plexuses intermingled with and established occasional contacts with GnRH fiber projections\n- Triple immunofluorescence revealed considerable overlap of KP, NKB, and SP signals within individual fibers, confirming they arise from the same mediobasal hypothalamic neurons\n- These anatomical relationships support axo-axonal communication between neuropeptide fibers and GnRH projections in humans","whyItMatters":"GnRH is the master hormone controlling reproduction, and understanding how it's regulated in the human brain is crucial for treating infertility, menopause, and reproductive disorders. This study provides the first detailed map of how key regulatory neuropeptides contact GnRH projections in humans — essential anatomical data for developing peptide-based reproductive therapies.","specificNumbers":"","methodology":"Immunohistochemical studies using single and triple-immunofluorescent labeling on histological brain samples from postmenopausal women. KP, NKB, SP, and GnRH were visualized to map their anatomical relationships in the postinfundibular eminence, infundibular stalk, and neurohypophysis.","limitations":"The study used tissue from postmenopausal women, who have altered neuropeptide levels compared to premenopausal women. Contact observations were anatomical — functional signaling at these contacts was not demonstrated. The study could not determine whether the observed contacts represent functional synapses. Only tissue availability from deceased donors was used, limiting sample diversity."},{"rthcId":"RPEP-02338","title":"Davunetide in patients with progressive supranuclear palsy: a randomised, double-blind, placebo-controlled phase 2/3 trial.","authors":"Boxer, Adam L; Lang, Anthony E; Grossman, Murray; Knopman, David S; Miller, Bruce L; Schneider, Lon S; Doody, Rachelle S; Lees, Andrew; Golbe, Lawrence I; Williams, David R; Corvol, Jean-Cristophe; Ludolph, Albert; Burn, David; Lorenzl, Stefan; Litvan, Irene; Roberson, Erik D; Höglinger, Günter U; Koestler, Mary; Jack, Clifford R; Van Deerlin, Viviana; Randolph, Christopher; Lobach, Iryna V; Heuer, Hilary W; Gozes, Illana; Parker, Lesley; Whitaker, Steve; Hirman, Joe; Stewart, Alistair J; Gold, Michael; Morimoto, Bruce H","year":2014,"journal":"The Lancet. Neurology, 13(7), 676-85","doi":"10.1016/S1474-4422(14)70088-2","pmid":"24873720","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02339","title":"Anti-Müllerian hormone: ovarian reserve testing and its potential clinical implications.","authors":"Broer, Simone L; Broekmans, Frank J M; Laven, Joop S E; Fauser, Bart C J M","year":2014,"journal":"Human reproduction update, 20(5), 688-701","doi":"10.1093/humupd/dmu020","pmid":"24821925","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02340","title":"The structure of lactoferrin-binding protein B from Neisseria meningitidis suggests roles in iron acquisition and neutralization of host defences.","authors":"Brooks, Cory L; Arutyunova, Elena; Lemieux, M Joanne","year":2014,"journal":"Acta crystallographica. Section F, Structural biology communications, 70(Pt 10), 1312-7","doi":"10.1107/S2053230X14019372","pmid":"25286931","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02341","title":"Synthesis of new potent agonistic analogs of growth hormone-releasing hormone (GHRH) and evaluation of their endocrine and cardiac activities.","authors":"Cai, Renzhi; Schally, Andrew V; Cui, Tengjiao; Szalontay, Luca; Halmos, Gabor; Sha, Wei; Kovacs, Magdolna; Jaszberenyi, Miklos; He, Jinlin; Rick, Ferenc G; Popovics, Petra; Kanashiro-Takeuchi, Rosemeire; Hare, Joshua M; Block, Norman L; Zarandi, Marta","year":2014,"journal":"Peptides, 52, 104-12","doi":"10.1016/j.peptides.2013.12.010","pmid":"24373935","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02342","title":"Hypotensive effects of ghrelin receptor agonists mediated through a novel receptor.","authors":"Callaghan, Brid; Kosari, Samin; Pustovit, Ruslan V; Sartor, Daniela M; Ferens, Dorota; Ban, Kung; Baell, Jonathan; Nguyen, Trung V; Rivera, Leni R; Brock, James A; Furness, John B","year":2014,"journal":"British journal of pharmacology, 171(5), 1275-86","doi":"10.1111/bph.12527","pmid":"24670149","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Three GHSR1a agonists (ulimorelin, capromorelin, CP464709) caused rapid blood pressure decreases in anesthetized rats. This effect was NOT blocked by GHSR1a antagonists (JMV2959 or YIL781) at doses that blocked other ghrelin receptor effects. Neither ghrelin nor unacylated ghrelin mimicked the hypotensive effect. The blood pressure drop preceded changes in sympathetic nerve activity and was not reduced by ganglionic blockade or baroreceptor denervation, indicating a direct vascular mechanism. Ulimorelin relaxed isolated mesenteric artery and aorta segments, with relaxation also resistant to GHSR1a antagonists. These findings indicate a novel vascular receptor activated by small-molecule GHSR1a agonists but not by the peptide ghrelin.","whyItMatters":"This study reveals that some drugs designed to target ghrelin receptors (for appetite stimulation or GI motility) have unexpected cardiovascular effects through a completely different receptor system. This matters for drug safety — blood pressure drops are a clinically important side effect. It also identifies a new blood vessel receptor that could become a target for blood pressure medications, potentially opening a novel therapeutic avenue for hypertension.","specificNumbers":"","methodology":"In vivo blood pressure studies in anesthetized rats using direct arterial monitoring, with pharmacological antagonism (JMV2959, YIL781), ganglionic blockade (hexamethonium), and sino-aortic denervation. Ex vivo relaxation studies on isolated rat mesenteric artery and aorta segments. In vitro GHSR1a activation assays in transfected HEK293 cells confirming drug potency at the known receptor. Multiple agonists and antagonists used to dissect the pharmacology.","limitations":"The study was conducted entirely in rats, and the novel receptor has not been identified or characterized molecularly. The blood pressure effects were studied under anesthesia, which may alter cardiovascular pharmacology. The receptor identity remains unknown — it could be a known receptor with unexpected pharmacology or a truly novel entity. Translation to human cardiovascular physiology is uncertain. The study used only small-molecule agonists; a broader panel of ghrelin-related peptides was not tested."},{"rthcId":"RPEP-02343","title":"Novel and conventional receptors for ghrelin, desacyl-ghrelin, and pharmacologically related compounds.","authors":"Callaghan, Brid; Furness, John B","year":2014,"journal":"Pharmacological reviews, 66(4), 984-1001","doi":"10.1124/pr.113.008433","pmid":"25107984","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Beyond the known ghrelin receptor GHSR1a, evidence points to at least two additional classes of receptors: ghrelin receptor-like receptors (GRLRs) that respond to both ghrelin and its unacylated form (UAG), and UAG-specific receptors that respond only to unacylated ghrelin. These novel receptors may be heterodimers formed when GHSR1a or GHSR1b pairs with other G protein-coupled receptors, creating complexes with distinct pharmacological properties.\n\nEffects mediated through these novel receptors include fat cell lipid accumulation, muscle cell differentiation, bone cell proliferation, insulin release, heart protection, blood vessel constriction and growth, and tumor cell proliferation — none of which can be fully explained by GHSR1a alone.","whyItMatters":"Ghrelin is one of the most important peptide hormones in metabolism, appetite regulation, and growth hormone release. Discovering that it acts through multiple previously unknown receptors fundamentally expands our understanding of how this peptide works in the body and opens new therapeutic targets for conditions ranging from obesity to heart disease to cancer.","specificNumbers":"1 known receptor (GHSR1a) · 2 proposed novel receptor classes (GRLRs, UAG receptors) · 1 identified novel receptor (CD36) · 8+ biological effects attributed to novel receptors","methodology":"This was a comprehensive review of published literature critically evaluating evidence for ghrelin receptor ligand effects that cannot be explained by action at the known GHSR1a receptor. The authors analyzed studies involving receptor expression detection, gene knockout models, and competitive binding assays.","limitations":"Most proposed novel receptors have not been molecularly identified, making it difficult to design targeted drugs. The heterodimer hypothesis, while plausible, remains largely unproven. Much of the evidence for novel receptors comes from indirect observations such as effects persisting after GHSR1a gene knockout rather than direct receptor identification."},{"rthcId":"RPEP-02344","title":"Small molecule ghrelin receptor inverse agonists and antagonists.","authors":"Cameron, Kimberly O; Bhattacharya, Samit K; Loomis, A Katrina","year":2014,"journal":"Journal of medicinal chemistry, 57(21), 8671-91","doi":"10.1021/jm5003183","pmid":"25036503","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02345","title":"Complete regression and systemic protective immune responses obtained in B16 melanomas after treatment with LTX-315.","authors":"Camilio, Ketil André; Berge, Gerd; Ravuri, Chandra Sekhar; Rekdal, Oystein; Sveinbjørnsson, Baldur","year":2014,"journal":"Cancer immunology, immunotherapy : CII, 63(6), 601-13","doi":"10.1007/s00262-014-1540-0","pmid":"24676901","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02346","title":"Peptide affinity chromatography based on combinatorial strategies for protein purification.","authors":"Camperi, Silvia Andrea; Martínez-Ceron, María Camila; Giudicessi, Silvana Laura; Marani, Mariela Mirta; Albericio, Fernando; Cascone, Osvaldo","year":2014,"journal":"Methods in molecular biology (Clifton, N.J.), 1129, 277-302","doi":"10.1007/978-1-62703-977-2_22","pmid":"24648083","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02347","title":"Lanreotide in metastatic enteropancreatic neuroendocrine tumors.","authors":"Caplin, Martyn E; Pavel, Marianne; Cwikla, Jaroslaw B; Phan, Alexandria T; Raderer, Markus; Sedlackova, Eva; Cadiot, Guillaume; Wolin, Edward M; Capdevila, Jaume; Wall, Lucy; Rindi, Guido; Langley, Alison; Martinez, Santiago; Blumberg, Jochen; Ruszniewski, Philippe; CLARINET Investigators","year":2014,"journal":"The New England journal of medicine, 371(3), 224-33","doi":"10.1056/NEJMoa1316158","pmid":"25014687","tags":["somatostatin-analogs","lanreotide","neuroendocrine-tumors","cancer"],"studyType":"human-rct","evidenceStrength":"strong","keyFinding":"In the landmark CLARINET trial, lanreotide (a long-acting somatostatin analog) cut the risk of tumor progression or death by 53% compared to placebo in patients with metastatic neuroendocrine tumors of the gut and pancreas (hazard ratio 0.47, p<0.001). After 96 weeks, 65.1% of lanreotide patients had no disease progression compared to just 33.0% on placebo.\n\nThe median progression-free survival wasn't even reached in the lanreotide group (vs. 18 months for placebo), meaning more than half the patients were still progression-free at study end. The treatment effect was consistent across subgroups, and quality of life was similar between groups.","whyItMatters":"CLARINET was the definitive trial that established lanreotide as a first-line antiproliferative treatment for well-differentiated neuroendocrine tumors, directly leading to FDA approval. Before this study, somatostatin analogs were primarily used for symptom control; CLARINET proved they actually slow tumor growth. Published in the New England Journal of Medicine, this is one of the most important studies in neuroendocrine tumor treatment.","specificNumbers":"n=204 · 96 weeks · HR 0.47 (95% CI 0.30–0.73) · p<0.001 · PFS at 24 months: 65.1% vs 33.0% · Median PFS: not reached vs 18.0 months · Diarrhea: 26% · Abdominal pain: 14%","methodology":"Phase 3, double-blind, placebo-controlled, multinational trial (CLARINET). 204 patients with well-differentiated or moderately differentiated, nonfunctioning, somatostatin receptor-positive, grade 1 or 2 (Ki-67 <10%) metastatic enteropancreatic neuroendocrine tumors were randomized to lanreotide 120 mg or placebo injected every 28 days for 96 weeks. Primary endpoint was progression-free survival.","limitations":"Only included grade 1/2 tumors (Ki-67 <10%) — results may not apply to more aggressive grade 3 neuroendocrine tumors. Only nonfunctioning tumors were included (those not producing excess hormones). Many patients had stable disease at entry, which could bias toward favorable outcomes. The study did not demonstrate an overall survival benefit."},{"rthcId":"RPEP-02348","title":"Coinfusion of low-dose GLP-1 and glucagon in man results in a reduction in food intake.","authors":"Cegla, Jaimini; Troke, Rachel C; Jones, Ben; Tharakan, George; Kenkre, Julia; McCullough, Katherine A; Lim, Chung Thong; Parvizi, Nassim; Hussein, Mohamed; Chambers, Edward S; Minnion, James; Cuenco, Joyceline; Ghatei, Mohammad A; Meeran, Karim; Tan, Tricia M; Bloom, Stephen R","year":2014,"journal":"Diabetes, 63(11), 3711-20","doi":"10.2337/db14-0242","pmid":"24939425","tags":[],"studyType":"Randomized Double-Blind Crossover Trial","evidenceStrength":"Moderate-High","keyFinding":"When GLP-1 and glucagon were each given at doses too low to reduce appetite on their own (subanorectic doses), combining them produced a significant 13% reduction in food intake compared to placebo. Additionally, GLP-1 protected against glucagon's tendency to raise blood sugar, and the combination increased resting energy expenditure by 53 kcal/day.\n\nThis demonstrates a synergistic interaction between the two peptides at low doses: neither alone was effective, but together they reduced appetite, prevented hyperglycemia, and boosted metabolic rate — providing a proof-of-concept for dual GLP-1/glucagon agonist drugs.","whyItMatters":"This study is one of the foundational human experiments supporting the development of dual GLP-1/glucagon agonist drugs for obesity. It showed that at carefully calibrated doses, the two peptides complement each other perfectly: GLP-1 handles the appetite reduction and blood sugar protection while glucagon adds energy expenditure boosting. This is the rationale behind drugs like survodutide and other dual agonists now in clinical development.","specificNumbers":"n=13 · 13% food intake reduction on combination · 53 kcal/day increase in resting energy expenditure · 120-minute infusions · Ad libitum meal at 90 minutes · Double-blind crossover · 4 conditions (GLP-1, glucagon, combo, placebo)","methodology":"Thirteen healthy volunteers received four separate 120-minute intravenous infusions in a double-blind, randomized crossover design: low-dose GLP-1 alone, low-dose glucagon alone, both peptides combined, or saline placebo. After 90 minutes, participants ate an ad libitum meal and caloric intake was measured. Resting energy expenditure was assessed by indirect calorimetry at baseline and during infusion. Blood glucose was monitored throughout.","limitations":"Small sample of 13 healthy volunteers — not obese or diabetic individuals who would be the target population for dual agonist therapy. The acute single-session design doesn't capture chronic treatment effects. Intravenous infusion doesn't mimic the pharmacokinetics of subcutaneous drug administration. The 53 kcal/day increase in energy expenditure is modest and may not be clinically meaningful. Only male volunteers are mentioned in the MeSH terms."},{"rthcId":"RPEP-02349","title":"Gut hormone activity of children born to women with and without gestational diabetes.","authors":"Chandler-Laney, P C; Bush, N C; Rouse, D J; Mancuso, M S; Gower, B A","year":2014,"journal":"Pediatric obesity, 9(1), 53-62","doi":"10.1111/j.2047-6310.2012.00140.x","pmid":"23364910","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02350","title":"Pentadecapeptide BPC 157 enhances the growth hormone receptor expression in tendon fibroblasts.","authors":"Chang, Chung-Hsun; Tsai, Wen-Chung; Hsu, Ya-Hui; Pang, Jong-Hwei Su","year":2014,"journal":"Molecules (Basel, Switzerland), 19(11), 19066-77","doi":"10.3390/molecules191119066","pmid":"25415472","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02351","title":"Expression of substance P, calcitonin gene-related peptide, β-endorphin and methionine-enkephalin in human dental pulp tissue after orthodontic intrusion: a pilot study.","authors":"Chavarría-Bolaños, Daniel; Martinez-Zumaran, Alan; Lombana, Nelson; Flores-Reyes, Hector; Pozos-Guillen, Amaury","year":2014,"journal":"The Angle orthodontist, 84(3), 521-6","doi":"10.2319/060313-423.1","pmid":"23987242","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02352","title":"Improved chemical synthesis of hydrophobic Aβ peptides using addition of C-terminal lysines later removed by carboxypeptidase B.","authors":"Chemuru, Saketh; Kodali, Ravindra; Wetzel, Ronald","year":2014,"journal":"Biopolymers, 102(2), 206-21","doi":"10.1002/bip.22470","pmid":"24488729","tags":[],"studyType":"laboratory","evidenceStrength":"low","keyFinding":"A new method for synthesizing hydrophobic amyloid-beta peptides was developed by temporarily adding lysine residues to the C-terminus during synthesis, then removing them enzymatically with carboxypeptidase B. This produced Aβ42 of quality rivaling recombinant expression — a significant improvement over standard synthesis.\n\nThe method also enabled synthesis of Aβ46, which was found to form amyloid fibrils significantly faster than Aβ42 or Aβ40. Despite being present in low amounts in the human brain, Aβ46's enhanced amyloidogenicity suggests it could play a disproportionate role in initiating Alzheimer's plaque formation.","whyItMatters":"Alzheimer's research depends on having pure, well-characterized amyloid-beta peptides. The more toxic Aβ42 has been notoriously difficult to synthesize chemically. This method solves a practical bottleneck in Alzheimer's research and also reveals that Aβ46 — a less-studied variant — may be an important early driver of plaque formation.","specificNumbers":"Aβ42 and Aβ46 synthesized · Quality rivals recombinant expression · Aβ46 aggregates faster than Aβ42 or Aβ40 · CPB-mediated Lys removal · Applicable to any sequence not ending in Arg/Lys","methodology":"Chemical synthesis study using Fmoc solid-phase peptide synthesis with C-terminal lysine additions. Post-purification enzymatic removal of lysines using immobilized carboxypeptidase B. Product quality verified by HPLC and mass spectrometry. Amyloid formation kinetics of the synthesized peptides (Aβ40, Aβ42, Aβ46) were characterized.","limitations":"This is a chemistry methods paper focused on synthesis quality. The biological significance of Aβ46 is speculative based on in vitro aggregation kinetics only. The method cannot be used for peptides naturally ending in arginine or lysine. No cell-based or in vivo validation of the synthesized peptides' biological activity was performed."},{"rthcId":"RPEP-02353","title":"μ-Opioid receptor inhibition of substance P release from primary afferents disappears in neuropathic pain but not inflammatory pain.","authors":"Chen, W; McRoberts, J A; Marvizón, J C G","year":2014,"journal":"Neuroscience, 267, 67-82","doi":"10.1016/j.neuroscience.2014.02.023","pmid":"24583035","tags":[],"studyType":"animal study","evidenceStrength":"low","keyFinding":"Nerve injury completely abolished the ability of μ-opioid receptors to inhibit substance P release from pain-sensing nerve fibers in the spinal cord of rats — explaining why opioids work poorly for neuropathic pain. In contrast, this opioid-mediated inhibition of substance P release remained intact in rats with inflammatory pain and in untreated rats. The loss of opioid control was not caused by fewer opioid receptors on nerve fibers — their numbers remained unchanged. Instead, the opioid receptors appeared to lose their ability to signal properly after nerve injury, even though they were still physically present.","whyItMatters":"It's a well-known clinical problem that opioids are much less effective for neuropathic pain (from nerve damage) than for inflammatory pain. This study provides a molecular explanation: nerve injury disrupts the opioid receptor's ability to suppress the release of substance P — a key pain-transmitting neuropeptide — in the spinal cord. Understanding this mechanism could lead to strategies to restore opioid sensitivity in neuropathic pain or to develop alternative approaches that bypass this broken signaling pathway.","specificNumbers":"Complete loss of DAMGO (μ-opioid agonist) inhibition of SP release in CCI rats · Normal inhibition preserved in CFA inflammatory pain · μ-opioid receptor expression unchanged on primary afferents","methodology":"Researchers used rats with chronic constriction injury (CCI) of the sciatic nerve as a neuropathic pain model and complete Freund's adjuvant (CFA) injection as an inflammatory pain model. Substance P release in the spinal cord was measured indirectly by tracking NK1 receptor internalization — when substance P is released, it binds NK1 receptors, which are then pulled inside the cell. The μ-opioid agonist DAMGO was tested for its ability to inhibit substance P release in spinal cord slices. Opioid receptor expression was assessed by immunofluorescence colocalization with substance P in dorsal root ganglion neurons.","limitations":"This is a rat study using an indirect measure of substance P release (NK1 receptor internalization). The CCI model, while well-established, may not perfectly replicate all forms of human neuropathic pain. The study demonstrates loss of opioid receptor signaling but does not fully elucidate the specific signaling mechanisms that are disrupted. The findings are specific to μ-opioid receptors and substance P — other opioid receptors and neurotransmitter systems may be affected differently."},{"rthcId":"RPEP-02354","title":"Effect of intravenous general anaesthesia with epidural block on the expression of pre-endogenous opioid peptide genes.","authors":"Chen, Zhi-Yang; Wang, Huaqing; Xu, Weiping; Xu, Hui; Fu, Xinchun","year":2014,"journal":"The Journal of international medical research, 42(3), 765-72","doi":"10.1177/0300060513515642","pmid":"24743873","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02355","title":"Designing unconventional Fmoc-peptide-based biomaterials: structure and related properties.","authors":"Chronopoulou, Laura; Sennato, Simona; Bordi, Federico; Giannella, Domenico; Di Nitto, Antonio; Barbetta, Andrea; Dentini, Mariella; Togna, Anna Rita; Togna, Giuseppina Ines; Moschini, Sabina; Palocci, Cleofe","year":2014,"journal":"Soft matter, 10(12), 1944-52","doi":"10.1039/c3sm52457d","pmid":"24651999","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02356","title":"Evaluation of mechanical properties and therapeutic effect of injectable self-assembling hydrogels for spinal cord injury.","authors":"Cigognini, Daniela; Silva, Diego; Paloppi, Sara; Gelain, Fabrizio","year":2014,"journal":"Journal of biomedical nanotechnology, 10(2), 309-23","doi":null,"pmid":"24738339","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02357","title":"Oxytocin and bone.","authors":"Colaianni, Graziana; Sun, Li; Zaidi, Mone; Zallone, Alberta","year":2014,"journal":"American journal of physiology. Regulatory, integrative and comparative physiology, 307(8), R970-7","doi":"10.1152/ajpregu.00040.2014","pmid":"25209411","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02358","title":"Hydrolysates of sheep cheese whey as a source of bioactive peptides with antioxidant and angiotensin-converting enzyme inhibitory activities.","authors":"Corrêa, Ana Paula Folmer; Daroit, Daniel Joner; Fontoura, Roberta; Meira, Stela Maris Meister; Segalin, Jeferson; Brandelli, Adriano","year":2014,"journal":"Peptides, 61, 48-55","doi":"10.1016/j.peptides.2014.09.001","pmid":"25218972","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02359","title":"Design and activity of novel lactoferrampin analogues against O157:H7 enterohemorrhagic Escherichia coli.","authors":"Cruz, Jenniffer; Ortiz, Claudia; Guzmán, Fanny; Cárdenas, Constanza; Fernandez-Lafuente, Roberto; Torres, Rodrigo","year":2014,"journal":"Biopolymers, 101(4), 319-28","doi":"10.1002/bip.22360","pmid":"23877962","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02360","title":"Anamorelin hydrochloride in the treatment of cancer anorexia-cachexia syndrome.","authors":"Currow, David C; Abernethy, Amy P","year":2014,"journal":"Future oncology (London, England), 10(5), 789-802","doi":"10.2217/fon.14.14","pmid":"24472001","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Anamorelin hydrochloride demonstrated significant improvements across multiple cachexia endpoints in preclinical and clinical studies:\n\n- Significant appetite enhancement via potent ghrelin receptor activation\n- Improvements in body weight and lean body mass compared to placebo\n- Improvements in handgrip strength (a key functional measure)\n- Stimulation of growth hormone and IGF-1 secretion (anabolic effects)\n\nCritically, the growth hormone and IGF-1 stimulation did not promote tumor growth, and overall survival was not compromised in cancer patients. The drug was well tolerated with no dose-limiting toxicities identified across studies completed at the time of this review. Phase III studies in non-small-cell lung cancer cachexia were ongoing.","whyItMatters":"Cancer cachexia affects up to 80% of advanced cancer patients and directly contributes to mortality, yet treatment options remain extremely limited. An oral drug that can improve appetite, build lean mass, and increase strength without promoting tumor growth or requiring injections would represent a major advance in supportive cancer care. Anamorelin's ghrelin-mimicking mechanism addresses the biological root of cachexia rather than just treating symptoms.","specificNumbers":"","methodology":"This is a review article summarizing preclinical and clinical study data for anamorelin hydrochloride in the treatment of cancer anorexia-cachexia syndrome, focusing on its application in non-small-cell lung cancer patients. The review covers pharmacology, efficacy data, safety profile, and the status of ongoing Phase III clinical trials.","limitations":"This is a review article published while Phase III trials were still ongoing, so definitive efficacy conclusions could not be drawn. The review focuses specifically on NSCLC cachexia, and generalizability to other cancer types was not established. Long-term safety data were limited. The review does not report specific numerical results from clinical trials in the abstract."},{"rthcId":"RPEP-02361","title":"Related impurities in peptide medicines.","authors":"D'Hondt, Matthias; Bracke, Nathalie; Taevernier, Lien; Gevaert, Bert; Verbeke, Frederick; Wynendaele, Evelien; De Spiegeleer, Bart","year":2014,"journal":"Journal of pharmaceutical and biomedical analysis, 101, 2-30","doi":"10.1016/j.jpba.2014.06.012","pmid":"25044089","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Peptide drug impurities fall into three categories: (1) synthesis-related impurities from solid-phase peptide synthesis (SPPS) — including amino acid deletions, insertions, racemization, incomplete side-chain deprotection, oxidation, and dimerization; (2) degradation products from chemical instability — including β-elimination, diketopiperazine formation, pyroglutamate formation, and succinimide formation; (3) finished product impurities from API-excipient interactions. Trifluoroacetate (TFA) counter-ion contamination from SPPS purification and cross-contamination with unrelated peptides (indicating inadequate GMP) were also documented.","whyItMatters":"With the peptide drug market growing twice as fast as other drug categories, understanding and controlling impurities is critical for patient safety. These impurities can affect drug efficacy, cause allergic reactions, or produce misleading results in early drug discovery. For compounded peptides (which lack the same quality controls as FDA-approved products), impurity risks are even greater. This review provides a comprehensive catalog of what can go wrong during peptide manufacturing.","specificNumbers":"Peptide market: growing 2× faster than other drug markets · 3 impurity categories · SPPS is primary manufacturing method · TFA counter-ion contamination documented · Cross-contamination = GMP failure indicator","methodology":"Comprehensive literature review cataloging all known types of peptide-related impurities in both active pharmaceutical ingredients and finished drug products, organized by their origin: synthesis-related, degradation-related, or formulation-related.","limitations":"This is a review article from 2014 — newer synthesis techniques and quality control methods may have addressed some of the impurity challenges described. The review focuses primarily on SPPS-manufactured peptides, which is the dominant method but not the only one (recombinant peptide production has different impurity profiles). Specific impurity levels and acceptable thresholds vary by regulatory jurisdiction and aren't comprehensively covered."},{"rthcId":"RPEP-02362","title":"Nasal oxytocin for social deficits in childhood autism: a randomized controlled trial.","authors":"Dadds, Mark R; MacDonald, Elayne; Cauchi, Avril; Williams, Katrina; Levy, Florence; Brennan, John","year":2014,"journal":"Journal of autism and developmental disorders, 44(3), 521-31","doi":"10.1007/s10803-013-1899-3","pmid":"23888359","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02363","title":"DPP-4 inhibitors repress NLRP3 inflammasome and interleukin-1beta via GLP-1 receptor in macrophages through protein kinase C pathway.","authors":"Dai, Yao; Dai, Dongsheng; Wang, Xianwei; Ding, Zufeng; Mehta, Jawahar L","year":2014,"journal":"Cardiovascular drugs and therapy, 28(5), 425-32","doi":"10.1007/s10557-014-6539-4","pmid":"25022544","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02364","title":"CSF and blood oxytocin concentration changes following intranasal delivery in macaque.","authors":"Dal Monte, Olga; Noble, Pamela L; Turchi, Janita; Cummins, Alex; Averbeck, Bruno B","year":2014,"journal":"PloS one, 9(8), e103677","doi":"10.1371/journal.pone.0103677","pmid":"25133536","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02365","title":"Lack of interleukin-17 leads to a modulated micro-environment and amelioration of mechanical hypersensitivity after peripheral nerve injury in mice.","authors":"Day, Yuan-Ji; Liou, Jiin-Tarng; Lee, Chiou-Mei; Lin, Yi-Chiao; Mao, Chih-Chieh; Chou, An-Hsun; Liao, Chia-Chih; Lee, Hung-Chen","year":2014,"journal":"Pain, 155(7), 1293-1302","doi":"10.1016/j.pain.2014.04.004","pmid":"24721689","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02366","title":"Relationship between levels of neuropeptide Substance P in periodontal disease and chronic pain: a literature review.","authors":"de Avila, Erica Dorigatti; de Molon, Rafael Scaf; de Godoi Gonçalves, Daniela Aparecida; Camparis, Cinara Maria","year":2014,"journal":"Journal of investigative and clinical dentistry, 5(2), 91-7","doi":"10.1111/jicd.12087","pmid":"24574025","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review consolidates evidence showing that Substance P is expressed during the inflammatory process of periodontal disease and contributes to alveolar bone resorption. Studies demonstrate that Substance P levels are highest in the gingival crevicular fluid from sites with active periodontal disease and bone loss.\n\nThe persistent presence of Substance P in periodontal tissues could stimulate neurogenic inflammation in susceptible tissues and cause pain. The review identifies Substance P expressed during periodontal disease as a potential risk factor for patients with systemic inflammatory pathologies, particularly chronic arthritis and rheumatoid arthritis, suggesting a neuropeptide-mediated link between oral and systemic inflammation.","whyItMatters":"The connection between gum disease and systemic health has become a major focus of medical research. This review identifies Substance P as a specific molecular link between oral inflammation and chronic pain conditions. If periodontal Substance P release contributes to systemic inflammation and pain, treating gum disease could potentially reduce chronic pain symptoms in conditions like arthritis — a possibility with significant clinical implications.","specificNumbers":"","methodology":"Literature review examining published studies on Substance P levels in periodontal disease, its role in pain signaling and bone resorption, and the connection between periodontal inflammation and systemic chronic pain conditions.","limitations":"This is a narrative literature review from 2014 that synthesizes existing studies without systematic methodology. The strength of the evidence linking periodontal Substance P to systemic chronic pain varies across the cited studies. Causation has not been established — elevated Substance P in periodontal disease could be a consequence rather than a cause of broader inflammatory processes. The review does not quantify the magnitude of Substance P elevations or the strength of the periodontal-pain association."},{"rthcId":"RPEP-02367","title":"Are incretin mimetics and enhancers linked to pancreatitis and malignant transformations in pancreas?","authors":"de Heer, Jocelyn; Göke, Burkhard","year":2014,"journal":"Expert opinion on drug safety, 13(11), 1469-81","doi":"10.1517/14740338.2014.955013","pmid":"25270593","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02368","title":"Driving h-osteoblast adhesion and proliferation on titania: peptide hydrogels decorated with growth factors and adhesive conjugates.","authors":"Dettin, M; Zamuner, A; Iucci, G; Messina, G M L; Battocchio, C; Picariello, G; Gallina, G; Marletta, G; Castagliuolo, I; Brun, P","year":2014,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 20(7), 585-94","doi":"10.1002/psc.2652","pmid":"24889357","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Self-assembling EAbuK peptide hydrogel layer on sandblasted/acid-etched titanium enhanced human osteoblast adhesion (with RGD conjugate at 3.8 × 10⁻⁷ M) and proliferation (with IGF-1 at 2.1 × 10⁻⁵ M). XPS confirmed surface composition changes; contact angle measurements showed altered wettability from the peptide layer.","whyItMatters":"Improving bone cell integration with titanium implants could reduce implant failure rates and accelerate healing after dental and orthopedic surgery — the peptide coating provides a bioactive surface that actively promotes bone formation.","specificNumbers":"Adhesion enhanced at RGD conjugate 3.8 × 10⁻⁷ M; proliferation enhanced at IGF-1 2.1 × 10⁻⁵ M; 4 GRGDSP motifs per chain; 25-residue conjugate","methodology":"Titanium surfaces were sandblasted and acid-etched, then covalently functionalized with EAbuK self-assembling peptide layer. Surfaces were enriched with IGF-1 and/or RGD-containing peptide conjugates. Surface characterization by XPS and contact angle. Human osteoblast adhesion and proliferation assays evaluated bioactivity.","limitations":"In vitro study only — no animal implant or clinical data. Only osteoblast adhesion and proliferation measured, not mineralization or bone formation. Specific concentrations of functional molecules were tested but optimal combinations not fully explored. Long-term coating stability on implants not assessed."},{"rthcId":"RPEP-02369","title":"αCGRP is essential for algesic exocytotic mobilization of TRPV1 channels in peptidergic nociceptors.","authors":"Devesa, Isabel; Ferrándiz-Huertas, Clotilde; Mathivanan, Sakthikumar; Wolf, Christoph; Luján, Rafael; Changeux, Jean-Pierre; Ferrer-Montiel, Antonio","year":2014,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 111(51), 18345-50","doi":"10.1073/pnas.1420252111","pmid":"25489075","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02370","title":"The physiology and clinical utility of anti-Mullerian hormone in women.","authors":"Dewailly, Didier; Andersen, Claus Yding; Balen, Adam; Broekmans, Frank; Dilaver, Nafi; Fanchin, Renato; Griesinger, Georg; Kelsey, Tom W; La Marca, Antonio; Lambalk, Cornelius; Mason, Helen; Nelson, Scott M; Visser, Jenny A; Wallace, W Hamish; Anderson, Richard A","year":2014,"journal":"Human reproduction update, 20(3), 370-85","doi":"10.1093/humupd/dmt062","pmid":"24430863","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02371","title":"Acylated and unacylated ghrelin protect MC3T3-E1 cells against tert-butyl hydroperoxide-induced oxidative injury: pharmacological characterization of ghrelin receptor and possible epigenetic involvement.","authors":"Dieci, Elisa; Casati, Lavinia; Pagani, Francesca; Celotti, Fabio; Sibilia, Valeria","year":2014,"journal":"Amino acids, 46(7), 1715-25","doi":"10.1007/s00726-014-1734-y","pmid":"24705647","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02372","title":"N-aminoimidazolidin-2-one peptidomimetics.","authors":"Doan, Ngoc-Duc; Hopewell, Robert; Lubell, William D","year":2014,"journal":"Organic letters, 16(8), 2232-5","doi":"10.1021/ol500739k","pmid":"24697286","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02373","title":"Gastrointestinal hormones and the dialogue between gut and brain.","authors":"Dockray, Graham J","year":2014,"journal":"The Journal of physiology, 592(14), 2927-41","doi":"10.1113/jphysiol.2014.270850","pmid":"24566540","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02374","title":"Inhibition and destruction of Pseudomonas aeruginosa biofilms by antibiotics and antimicrobial peptides.","authors":"Dosler, Sibel; Karaaslan, Elif","year":2014,"journal":"Peptides, 62, 32-7","doi":"10.1016/j.peptides.2014.09.021","pmid":"25285879","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02375","title":"A two-step strategy to enhance activity of low potency peptides.","authors":"Doyle, Jamie R; Harwood, Benjamin N; Krishnaji, Subrahmanian Tarakkad; Krishnamurthy, Vijay M; Lin, Wei-En; Fortin, Jean-Philippe; Kumar, Krishna; Kopin, Alan S","year":2014,"journal":"PloS one, 9(11), e110502","doi":"10.1371/journal.pone.0110502","pmid":"25391026","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02376","title":"Survival benefit of ghrelin in the heart failure due to dilated cardiomyopathy.","authors":"Du, Cheng-Kun; Zhan, Dong-Yun; Morimoto, Sachio; Akiyama, Tsuyoshi; Schwenke, Daryl O; Hosoda, Hiroshi; Kangawa, Kenji; Shirai, Mikiyasu","year":2014,"journal":"Pharmacology research & perspectives, 2(5), e00064","doi":"10.1002/prp2.64","pmid":"25505608","tags":["ghrelin","heart-failure","cardioprotection"],"studyType":"Preclinical (Animal Study)","evidenceStrength":"Preliminary","keyFinding":"Daily ghrelin injections significantly extended the lifespan of mice with inherited dilated cardiomyopathy (DCM) compared to saline-treated controls over a 30-day treatment period. Beyond survival, ghrelin improved multiple measures of heart function: it reduced left ventricular dilation, increased ejection fraction (the heart's pumping efficiency), decreased the heart-to-body weight ratio, prevented cardiac remodeling and fibrosis, and lowered brain natriuretic peptide (BNP) expression — a key marker of heart failure severity.\n\nThe mechanism appears to involve the autonomic nervous system: ghrelin suppressed the excessive sympathetic nerve activity that drives heart failure progression and restored parasympathetic (calming) nerve activity to the heart. This rebalancing of the nervous system may be central to ghrelin's cardioprotective effects.","whyItMatters":"Heart failure from dilated cardiomyopathy is a leading cause of death, and current treatments have limited ability to reverse the disease. This is the first study to demonstrate that ghrelin — the hunger hormone — can actually extend survival in a genetic heart failure model, not just improve symptoms. The mechanism involving sympathetic nerve suppression is particularly interesting because overactive sympathetic drive is a well-known accelerator of heart failure that current beta-blocker therapy only partially addresses.","specificNumbers":"Ghrelin 150 μg/kg/day SC · 30-day treatment from age 30 days · significantly prolonged survival · increased LV ejection fraction · reduced LV end-diastolic dimensions · decreased heart-to-body weight ratio · reduced BNP expression · suppressed cardiac sympathetic nerve activity","methodology":"Mice with inherited dilated cardiomyopathy (caused by a ΔK210 mutation in cardiac troponin T) received daily subcutaneous injections of ghrelin (150 μg/kg) or saline starting at 30 days of age for 30 days. Survival was compared between groups. After treatment, researchers performed echocardiography (heart ultrasound), histological analysis of heart tissue for remodeling and fibrosis, BNP expression measurement, and telemetry recording with heart rate variability analysis to assess autonomic nervous system activity.","limitations":"This is a mouse study using a specific genetic model of dilated cardiomyopathy that may not represent all forms of human heart failure. The 30-day treatment window is relatively short. Specific survival percentages and statistical values are not provided in the abstract. The ghrelin dose used may not translate directly to human dosing. Ghrelin's appetite-stimulating effects could complicate its use in heart failure patients. Long-term safety of daily ghrelin administration was not assessed."},{"rthcId":"RPEP-02377","title":"Pentadecapeptide BPC 157 and anaphylactoid reaction in rats and mice after intravenous dextran and white egg administration.","authors":"Duplancic, Bozidar; Stambolija, Vasilije; Holjevac, Jadranka; Zemba, Mladen; Balenovic, Igor; Drmic, Domagoj; Suran, Jelena; Radic, Bozo; Filipovic, Marinko; Blagaic, Alenka Boban; Brcic, Luka; Kolenc, Danijela; Grabarevic, Zeljko; Seiwerth, Sven; Sikiric, Predrag","year":2014,"journal":"European journal of pharmacology, 727, 75-9","doi":"10.1016/j.ejphar.2014.01.046","pmid":"24486708","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02378","title":"Molecular cloning, regulation, and functional analysis of two GHS-R genes in zebrafish.","authors":"Eom, Ji; Hong, Areum; Kang, Young-Ho; Yoo, Han-Ju; Chang, Eun-Ju; Kang, Sang-Wook; Yoon, Seung-Yong; Kim, Sang-Yeob; Song, Youngsup","year":2014,"journal":"Experimental cell research, 326(1), 10-21","doi":"10.1016/j.yexcr.2014.06.002","pmid":"24928276","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02379","title":"G Protein and β-arrestin signaling bias at the ghrelin receptor.","authors":"Evron, Tama; Peterson, Sean M; Urs, Nikhil M; Bai, Yushi; Rochelle, Lauren K; Caron, Marc G; Barak, Larry S","year":2014,"journal":"The Journal of biological chemistry, 289(48), 33442-55","doi":"10.1074/jbc.M114.581397","pmid":"25261469","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02380","title":"Prenatal stress, anxiety and depression: a mechanism involving CRH peptide family.","authors":"Fan, Jun-Ming; Chen, Xue-Qun; Du, Ji-Zeng","year":2014,"journal":"Neuro endocrinology letters, 35(6), 429-39","doi":null,"pmid":"25433848","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02381","title":"Endogenous peptides as risk markers to assess the development of insulin resistance.","authors":"Fang, Penghua; Shi, Mingyi; Yu, Mei; Guo, Lili; Bo, Ping; Zhang, Zhenwen","year":2014,"journal":"Peptides, 51, 9-14","doi":"10.1016/j.peptides.2013.10.025","pmid":"24184593","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02382","title":"Design and high-level expression of a hybrid antimicrobial peptide LF15-CA8 in Escherichia coli.","authors":"Feng, Xing-Jun; Xing, Li-Wei; Liu, Di; Song, Xue-Ying; Liu, Chun-Long; Li, Jing; Xu, Wen-Shan; Li, Zhong-Qiu","year":2014,"journal":"Journal of industrial microbiology & biotechnology, 41(3), 527-34","doi":"10.1007/s10295-013-1382-3","pmid":"24281395","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02383","title":"Antihypertensive mechanism of lactoferrin-derived peptides: angiotensin receptor blocking effect.","authors":"Fernández-Musoles, Ricardo; Castelló-Ruiz, María; Arce, Cristina; Manzanares, Paloma; Ivorra, M Dolores; Salom, Juan B","year":2014,"journal":"Journal of agricultural and food chemistry, 62(1), 173-81","doi":"10.1021/jf404616f","pmid":"24354413","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Lactoferrin-derived peptides, including LfcinB20-25 (RRWQWR), LIWKL, and RPYL, all inhibited angiotensin II-induced vasoconstriction in ex vivo assays. RPYL showed the highest inhibitory effect and was confirmed to directly block AT1 receptor binding using radioligand assays with [(125)I]-(Sar(1),Ile(8))-angiotensin II.\n\nImportantly, neither the lactoferrin hydrolysate nor RPYL inhibited endothelin-1 or depolarization-induced vasoconstriction, demonstrating selectivity for the angiotensin pathway. This represents a blood pressure-lowering mechanism beyond ACE inhibition that may work synergistically with it.","whyItMatters":"Most food-derived blood pressure-lowering peptides work by inhibiting ACE (the enzyme that makes angiotensin II). This study reveals that lactoferrin peptides can also block angiotensin receptors directly — the same mechanism used by prescription ARB drugs like losartan. Having multiple mechanisms of action could make lactoferrin-derived peptides more effective as natural blood pressure support.","specificNumbers":"","methodology":"The study used ex vivo vascular tissue assays to test lactoferricin B-derived peptide (LfcinB20-25), a low molecular weight lactoferrin hydrolysate (<3 kDa), and two peptides identified within the hydrolysate (LIWKL and RPYL) for their ability to inhibit vasoconstriction induced by angiotensin II, endothelin-1, or depolarization. RPYL was further tested in radioligand receptor binding assays to confirm direct AT1 receptor blockade.","limitations":"This is an ex vivo study using isolated vascular tissue, not a whole-animal or human study. The peptides' oral bioavailability and ability to reach blood vessels intact after digestion is unknown. Concentrations used in tissue assays may not reflect achievable physiological levels. Only a limited number of peptide sequences were tested from the lactoferrin hydrolysate."},{"rthcId":"RPEP-02384","title":"Adverse Effects of GLP-1 Receptor Agonists.","authors":"Filippatos, Theodosios D; Panagiotopoulou, Thalia V; Elisaf, Moses S","year":2014,"journal":"The review of diabetic studies : RDS, 11(3-4), 202-30","doi":"10.1900/RDS.2014.11.202","pmid":"26177483","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02385","title":"Potent inhibitors of human matriptase-1 based on the scaffold of sunflower trypsin inhibitor.","authors":"Fittler, Heiko; Avrutina, Olga; Empting, Martin; Kolmar, Harald","year":2014,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 20(6), 415-20","doi":"10.1002/psc.2629","pmid":"24723440","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02386","title":"Agonists of growth hormone-releasing hormone stimulate self-renewal of cardiac stem cells and promote their survival.","authors":"Florea, Victoria; Majid, Sonia S; Kanashiro-Takeuchi, Rosemeire M; Cai, Ren-Zhi; Block, Norman L; Schally, Andrew V; Hare, Joshua M; Rodrigues, Claudia O","year":2014,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 111(48), 17260-5","doi":"10.1073/pnas.1420375111","pmid":"25404316","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02387","title":"Estradiol modulates Kiss1 neuronal response to ghrelin.","authors":"Frazao, Renata; Dungan Lemko, Heather M; da Silva, Regina P; Ratra, Dhirender V; Lee, Charlotte E; Williams, Kevin W; Zigman, Jeffrey M; Elias, Carol F","year":2014,"journal":"American journal of physiology. Endocrinology and metabolism, 306(6), E606-14","doi":"10.1152/ajpendo.00211.2013","pmid":"24473434","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02388","title":"Rationally Designed Macrocyclic Peptides as Synergistic Agonists of LPS-Induced Inflammatory Response.","authors":"Gao, Meng; London, Nir; Cheng, Kui; Tamura, Ryo; Jin, Jialin; Schueler-Furman, Ora; Yin, Hang","year":2014,"journal":"Tetrahedron, 70(42), 7664-7668","doi":"10.1016/j.tet.2014.07.026","pmid":"25400297","tags":[],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Using computational design with Rosetta software, researchers created two macrocyclic (ring-shaped) peptides derived from the MD2 protein sequence that modulate TLR4 immune signaling. The cyclic peptides synergistically enhanced TLR4 activation when co-administered with LPS (bacterial endotoxin), while their linear (non-cyclized) counterparts had no such effect.\n\nThis demonstrates that peptide cyclization — making a linear peptide into a ring — can be critical for biological activity, and that computationally designed macrocyclic peptides can serve as tools for modulating innate immune signaling.","whyItMatters":"TLR4 is a central receptor in innate immunity and a drug target for conditions ranging from sepsis to cancer immunotherapy. This study demonstrates that rational computational design can produce macrocyclic peptides with defined immune-modulating activity — an approach that could accelerate development of peptide-based drugs for immune regulation. The finding that only cyclic, not linear, peptides were active highlights a key principle in peptide drug design.","specificNumbers":"","methodology":"Two macrocyclic peptides were designed computationally using the Rosetta Macromolecular Modeling software, based on sequences from the MD2 protein (a co-receptor for TLR4). Both cyclic and linear versions of the peptides were synthesized. Their effects on TLR4 signaling were tested in cell-based assays by co-administering the peptides with LPS and measuring inflammatory response activation.","limitations":"This is an in vitro study — the peptides have not been tested in animal models or humans. The mechanism of action remains unclear (the authors note it is 'elusive'). Only synergistic agonism (enhancing LPS response) was observed, not independent activation. The study is from 2014 and represents early-stage work in computational peptide design."},{"rthcId":"RPEP-02389","title":"Region specific up-regulation of oxytocin receptors in the opioid oprm1 (-/-) mouse model of autism.","authors":"Gigliucci, Valentina; Leonzino, Marianna; Busnelli, Marta; Luchetti, Alessandra; Palladino, Viola Stella; D'Amato, Francesca R; Chini, Bice","year":2014,"journal":"Frontiers in pediatrics, 2, 91","doi":"10.3389/fped.2014.00091","pmid":"25225634","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02390","title":"A systematic review of acute pancreatitis as an adverse event of type 2 diabetes drugs: from hard facts to a balanced position.","authors":"Giorda, C B; Nada, E; Tartaglino, B; Marafetti, L; Gnavi, R","year":2014,"journal":"Diabetes, obesity & metabolism, 16(11), 1041-7","doi":"10.1111/dom.12297","pmid":"24702687","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Case reports and the FDA pharmacovigilance database indicate associations between acute pancreatitis and incretin drugs (both DPP-4 inhibitors and GLP-1 receptor agonists). However, only 1 of 8 pharmacoepidemiological studies found a statistically significant odds ratio for this association. None of the intervention trials, including two large RCTs with cardiovascular endpoints, confirmed an increased pancreatitis risk with incretin use.\n\nOther diabetes drugs also have pancreatitis associations: metformin (in renal insufficiency), sulphonylureas (particularly glibenclamide), and phenformin have been linked in case reports or cohort studies. No link was found for metaglinide, acarbose, pramlintide, or SGLT-2 inhibitors. Thiazolidinediones may actually be protective in animal models.","whyItMatters":"The pancreatitis scare around GLP-1 drugs created significant concern among patients and clinicians, with some initial claims of up to 30-fold increased risk. This systematic review puts the evidence in perspective: while case reports exist, the highest-quality evidence (large RCTs) does not support an increased risk. This is reassuring for the millions of patients now taking GLP-1 peptide drugs for diabetes and obesity, though vigilance remains appropriate.","specificNumbers":"","methodology":"Systematic review searching medical databases for evidence linking acute pancreatitis to all type 2 diabetes drug classes, including biguanides, sulphonylureas, metaglinides, acarbose, thiazolidinediones, pramlintide, SGLT-2 inhibitors, DPP-4 inhibitors, and GLP-1 receptor agonists. Evidence was evaluated from case reports, pharmacovigilance databases, cohort studies, and randomized controlled trials.","limitations":"Published in 2014, this review predates the massive expansion of GLP-1 drug use for obesity and the availability of newer agents like semaglutide and tirzepatide. Some of the drugs discussed (phenformin) have been withdrawn. Drug-related pancreatitis is inherently rare and difficult to diagnose, making definitive conclusions challenging even with large studies. Confounding by diabetes severity and obesity is difficult to fully eliminate."},{"rthcId":"RPEP-02391","title":"Assessing interactions between Ghsr and Mc3r reveals a role for AgRP in the expression of food anticipatory activity in male mice.","authors":"Girardet, Clemence; Mavrikaki, Maria; Southern, Mark R; Smith, Roy G; Butler, Andrew A","year":2014,"journal":"Endocrinology, 155(12), 4843-55","doi":"10.1210/en.2014-1497","pmid":"25211592","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In a restricted feeding protocol, all three mutant groups (GhsrKO, Mc3rKO, and double knockouts) initially showed reduced food anticipatory activity. However, GhsrKO mice eventually developed a robust compensatory response, while Mc3rKO and double knockout mice did not recover. The continued FAA deficit in Mc3rKO mice was associated with lower expression of the orexigenic neuropeptides AgRP and NPY in the hypothalamus before mealtimes. AgRP and NPY expression positively correlated with FAA levels, and only Mc3r loss (not Ghsr loss) suppressed these hunger-signaling peptides, pointing to melanocortin-3 receptors as critical regulators of anticipatory hunger responses.","whyItMatters":"Understanding how the brain anticipates and prepares for meals is fundamental to appetite regulation and metabolic health. This study disentangles the roles of two important peptide signaling systems — ghrelin and melanocortins — showing they have distinct and non-redundant roles. The finding that melanocortin-3 receptors are essential (not just contributory) for maintaining food anticipation has implications for understanding eating disorders, meal timing, and metabolic conditions where appetite regulation is disrupted.","specificNumbers":"","methodology":"Researchers used knockout mice lacking the ghrelin receptor (GhsrKO), melanocortin-3 receptor (Mc3rKO), or both (DKO), and compared them to wild-type controls. Mice underwent hypocaloric restricted feeding protocols in both constant darkness and standard light-dark cycles. Locomotor activity was measured to quantify food anticipatory activity. Hypothalamic AgRP and NPY mRNA expression was measured by quantitative methods 1 hour before scheduled food presentation.","limitations":"This study used genetically engineered knockout mice, which lack these receptors from birth and may develop compensatory mechanisms not present in adult-onset receptor dysfunction. Only male mice were studied, limiting generalizability to females. The restricted feeding protocol is an artificial paradigm that may not fully represent natural eating behavior. Hypothalamic gene expression was measured at a single time point, which may miss dynamic changes in neuropeptide signaling."},{"rthcId":"RPEP-02392","title":"Ghrelin mimics fasting to enhance human hedonic, orbitofrontal cortex, and hippocampal responses to food.","authors":"Goldstone, Anthony P; Prechtl, Christina G; Scholtz, Samantha; Miras, Alexander D; Chhina, Navpreet; Durighel, Giuliana; Deliran, Seyedeh S; Beckmann, Christian; Ghatei, Mohammad A; Ashby, Damien R; Waldman, Adam D; Gaylinn, Bruce D; Thorner, Michael O; Frost, Gary S; Bloom, Stephen R; Bell, Jimmy D","year":2014,"journal":"The American journal of clinical nutrition, 99(6), 1319-30","doi":"10.3945/ajcn.113.075291","pmid":"24760977","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02393","title":"Selective DNA delivery to tumor cells using an oligoarginine-LTVSPWY peptide.","authors":"Gong, Cheng; Pan, Deng; Qiu, Fengwu; Sun, Pei; Zhang, Yu-Hui","year":2014,"journal":"PloS one, 9(10), e110632","doi":"10.1371/journal.pone.0110632","pmid":"25337703","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02394","title":"G protein-coupled receptor 120 signaling regulates ghrelin secretion in vivo and in vitro.","authors":"Gong, Zhi; Yoshimura, Makoto; Aizawa, Sayaka; Kurotani, Reiko; Zigman, Jeffrey M; Sakai, Takafumi; Sakata, Ichiro","year":2014,"journal":"American journal of physiology. Endocrinology and metabolism, 306(1), E28-35","doi":"10.1152/ajpendo.00306.2013","pmid":"24222669","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02395","title":"Effect of GLY-HIS-LYS and its copper complex on TGF-β secretion in normal human dermal fibroblasts.","authors":"Gruchlik, Arkadiusz; Chodurek, Ewa; Dzierzewicz, Zofia","year":2014,"journal":"Acta poloniae pharmaceutica, 71(6), 954-8","doi":null,"pmid":"25745767","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02396","title":"Treatment with LL-37 is safe and effective in enhancing healing of hard-to-heal venous leg ulcers: a randomized, placebo-controlled clinical trial.","authors":"Grönberg, Alvar; Mahlapuu, Margit; Ståhle, Mona; Whately-Smith, Caroline; Rollman, Ola","year":2014,"journal":"Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society, 22(5), 613-21","doi":"10.1111/wrr.12211","pmid":"25041740","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02397","title":"Probing the origin of structural stability of single and double stapled p53 peptide analogs bound to MDM2.","authors":"Guo, Zuojun; Streu, Kristina; Krilov, Goran; Mohanty, Udayan","year":2014,"journal":"Chemical biology & drug design, 83(6), 631-42","doi":"10.1111/cbdd.12284","pmid":"24418072","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The computational analysis revealed several key relationships between peptide stapling strategy and function:\n\n- α-helical conformation stability is critical for peptide-MDM2 binding\n- Peptide sequence, cross-linker stereochemistry, alkene bridge conformation, and bridge length all affect helical stability\n- WaterMap analysis identified over 100 hydration sites in the MDM2 binding pocket where displacing water releases binding free energy\n- Potentials of mean force correctly ranked peptide binding affinities in agreement with experimental data\n- Double staples can provide additional stability but the benefit depends on placement and chemistry\n\nThe study provides a comprehensive structure-activity relationship for stapled peptide design targeting the p53/MDM2 interaction.","whyItMatters":"Stapled peptides are one of the most promising approaches for targeting protein-protein interactions in cancer — traditionally considered 'undruggable.' The p53/MDM2 interaction is among the most important cancer targets, and several stapled peptide drugs are in clinical development. This computational framework helps predict which stapling strategies will produce the best drugs, potentially saving years of trial-and-error synthesis and accelerating drug development.","specificNumbers":"","methodology":"Computational study using molecular dynamics simulations and WaterMap analysis. The researchers modeled α-helical conformations of single and double stapled p53 peptide analogs, both free and bound to MDM2. They systematically varied peptide sequence, cross-linker stereochemistry, double bond conformation, and bridge length. Binding affinity was calculated using weighted histogram analysis methods (WHAM) for potentials of mean force, and validated against published experimental binding data.","limitations":"This is a purely computational study — no new peptides were synthesized or experimentally tested. Computational predictions, while validated against existing experimental data, have inherent limitations in accuracy. Force field parameters may not perfectly capture all aspects of peptide-protein interactions. The study focused specifically on p53/MDM2 and results may not directly transfer to other stapled peptide targets. Cellular permeability, metabolic stability, and in vivo efficacy were not addressed."},{"rthcId":"RPEP-02398","title":"Expression of gastrin-releasing peptide by excitatory interneurons in the mouse superficial dorsal horn.","authors":"Gutierrez-Mecinas, Maria; Watanabe, Masahiko; Todd, Andrew J","year":2014,"journal":"Molecular pain, 10, 79","doi":"10.1186/1744-8069-10-79","pmid":"25496164","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02399","title":"Genetic and biochemical evidence that recombinant Enterococcus spp. strains expressing gelatinase (GelE) produce bovine milk-derived hydrolysates with high angiotensin converting enzyme-inhibitory activity (ACE-IA).","authors":"Gútiez, Loreto; Borrero, Juan; Jiménez, Juan J; Gómez-Sala, Beatriz; Recio, Isidra; Cintas, Luis M; Herranz, Carmen; Hernández, Pablo E","year":2014,"journal":"Journal of agricultural and food chemistry, 62(24), 5555-64","doi":"10.1021/jf5006269","pmid":"24877744","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02400","title":"Cerebrolysin protects PC12 cells from CoCl2-induced hypoxia employing GSK3β signaling.","authors":"Hartwig, Kerstin; Fackler, Viktoria; Jaksch-Bogensperger, Heidi; Winter, Stefan; Furtner, Tanja; Couillard-Despres, Sebastien; Meier, Dieter; Moessler, Herbert; Aigner, Ludwig","year":2014,"journal":"International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience, 38, 52-8","doi":"10.1016/j.ijdevneu.2014.07.005","pmid":"25093704","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02401","title":"PET radiopharmaceuticals for imaging integrin expression: tracers in clinical studies and recent developments.","authors":"Haubner, Roland; Maschauer, Simone; Prante, Olaf","year":2014,"journal":"BioMed research international, 2014, 871609","doi":"10.1155/2014/871609","pmid":"25013808","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02402","title":"Monocytes from Sjögren's syndrome patients display increased vasoactive intestinal peptide receptor 2 expression and impaired apoptotic cell phagocytosis.","authors":"Hauk, V; Fraccaroli, L; Grasso, E; Eimon, A; Ramhorst, R; Hubscher, O; Pérez Leirós, C","year":2014,"journal":"Clinical and experimental immunology, 177(3), 662-70","doi":"10.1111/cei.12378","pmid":"24827637","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02403","title":"Vasoactive intestinal peptide induces an immunosuppressant microenvironment in the maternal-fetal interface of non-obese diabetic mice and improves early pregnancy outcome.","authors":"Hauk, Vanesa; Azzam, Sofía; Calo, Guillermina; Gallino, Lucila; Paparini, Daniel; Franchi, Ana; Ramhorst, Rosanna; Pérez Leirós, Claudia","year":2014,"journal":"American journal of reproductive immunology (New York, N.Y. : 1989), 71(2), 120-30","doi":"10.1111/aji.12167","pmid":"24405265","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Vasoactive intestinal peptide (VIP) improved early pregnancy outcomes in non-obese diabetic (NOD) mice by shifting the immune environment at the maternal-fetal interface toward tolerance. In vitro, VIP treatment of implantation sites increased expression of immunosuppressive markers IL-10, TGF-β, and Foxp3 (a marker of regulatory T cells). It also reduced expression of IL-17 and RORγT, markers associated with inflammatory immune responses. Resorption sites (where pregnancies were failing) had lower VIP expression and reduced suppressive markers compared to viable sites. When pregnant NOD mice were injected with VIP on gestational day 6.5, they showed a more even distribution of viable implantation sites with increased IL-10, TGF-β, and Foxp3 expression by day 9.5.","whyItMatters":"Pregnancy complications in autoimmune conditions like type 1 diabetes often involve the immune system attacking the developing placenta. This study shows that VIP — a naturally occurring peptide — can tip the immune balance at the maternal-fetal interface toward tolerance, potentially protecting pregnancies in autoimmune-prone individuals. It highlights VIP as a candidate for preventing immune-mediated pregnancy loss.","specificNumbers":"","methodology":"Researchers used NOD mice, a model for autoimmune diabetes. Implantation sites were isolated at gestational day 9.5 and treated with VIP in vitro. Gene and protein expression of cytokines (IL-10, TGF-β, IL-17) and transcription factors (Foxp3, RORγT) were measured using RT-PCR, immunoblotting, and immunohistochemistry. In a parallel experiment, pregnant NOD mice received VIP injections on day 6.5 and outcomes were assessed at day 9.5.","limitations":"This is an animal study using NOD mice, which model autoimmune diabetes but don't perfectly replicate human pregnancy complications. The VIP injection was given at a single time point, so the optimal timing and duration of treatment remain unknown. The study focused on early pregnancy (day 6.5–9.5), so later-stage effects were not assessed."},{"rthcId":"RPEP-02404","title":"Methylprednisolone prevents nerve injury-induced hyperalgesia in neprilysin knockout mice.","authors":"He, Lan; Üçeyler, Nurcan; Krämer, Heidrun H; Colaço, Maria Nandini; Lu, Bao; Birklein, Frank; Sommer, Claudia","year":2014,"journal":"Pain, 155(3), 574-580","doi":"10.1016/j.pain.2013.12.003","pmid":"24333776","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02405","title":"Stitched α-helical peptides via bis ring-closing metathesis.","authors":"Hilinski, Gerard J; Kim, Young-Woo; Hong, Jooyeon; Kutchukian, Peter S; Crenshaw, Charisse M; Berkovitch, Shaunna S; Chang, Andrew; Ham, Sihyun; Verdine, Gregory L","year":2014,"journal":"Journal of the American Chemical Society, 136(35), 12314-22","doi":"10.1021/ja505141j","pmid":"25105213","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02406","title":"Effects of delayed gastric emptying on postprandial glucose kinetics, insulin sensitivity, and β-cell function.","authors":"Hinshaw, Ling; Schiavon, Michele; Mallad, Ashwini; Man, Chiara Dalla; Basu, Rita; Bharucha, Adil E; Cobelli, Claudio; Carter, Rickey E; Basu, Ananda; Kudva, Yogish C","year":2014,"journal":"American journal of physiology. Endocrinology and metabolism, 307(6), E494-502","doi":"10.1152/ajpendo.00199.2014","pmid":"25074985","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02407","title":"Melanoma associated with the use of melanotan-II.","authors":"Hjuler, Kasper Fjellhaugen; Lorentzen, Henrik Frank","year":2014,"journal":"Dermatology (Basel, Switzerland), 228(1), 34-6","doi":"10.1159/000356389","pmid":"24355990","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02408","title":"Targeted therapy in advanced metastatic colorectal cancer: current concepts and perspectives.","authors":"Hohla, Florian; Winder, Thomas; Greil, Richard; Rick, Ferenc G; Block, Norman L; Schally, Andrew V","year":2014,"journal":"World journal of gastroenterology, 20(20), 6102-12","doi":"10.3748/wjg.v20.i20.6102","pmid":"24876732","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies multiple peptide systems involved in colorectal cancer growth:\n\n- Gastrin and gastrin-releasing peptide (GRP/bombesin) promote CRC growth\n- Insulin-like growth factor I and II are implicated in CRC progression\n- Growth hormone-releasing hormone (GHRH) contributes to tumor growth\n\nExperimental approaches include antagonistic analogs of bombesin/GRP, GHRH antagonists, and cytotoxic peptides that target peptide receptors on tumors to deliver chemotherapy directly to cancer cells. These peptide-based strategies complement existing VEGF and EGFR-targeting therapies.","whyItMatters":"Most patients with metastatic colorectal cancer eventually develop resistance to current therapies. Peptide-based approaches targeting tumor growth signaling through different pathways could provide new treatment options. Cytotoxic peptides that deliver drugs specifically to tumor cells via peptide receptors are particularly promising for reducing side effects.","specificNumbers":"","methodology":"This is a narrative review published in the World Journal of Gastroenterology, summarizing clinical data on established VEGF and EGFR-targeting regimens and preclinical/experimental data on peptide-based targeted approaches for metastatic colorectal cancer.","limitations":"Published in 2014, many of the peptide-based approaches discussed were still experimental at the time. The review mixes well-established clinical data (VEGF/EGFR targeting) with early-stage preclinical peptide research. Clinical trial results for the peptide approaches were limited or absent at the time of publication."},{"rthcId":"RPEP-02409","title":"3-D self-assembling leucine zipper hydrogel with tunable properties for tissue engineering.","authors":"Huang, Chun-Chieh; Ravindran, Sriram; Yin, Ziying; George, Anne","year":2014,"journal":"Biomaterials, 35(20), 5316-5326","doi":"10.1016/j.biomaterials.2014.03.035","pmid":"24713184","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02410","title":"Chronic and acute intranasal oxytocin produce divergent social effects in mice.","authors":"Huang, Huiping; Michetti, Caterina; Busnelli, Marta; Managò, Francesca; Sannino, Sara; Scheggia, Diego; Giancardo, Luca; Sona, Diego; Murino, Vittorio; Chini, Bice; Scattoni, Maria Luisa; Papaleo, Francesco","year":2014,"journal":"Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 39(5), 1102-14","doi":"10.1038/npp.2013.310","pmid":"24190025","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02411","title":"Therapies for inter-relating diabetes and obesity - GLP-1 and obesity.","authors":"Iepsen, Eva W; Torekov, Signe S; Holst, Jens J","year":2014,"journal":"Expert opinion on pharmacotherapy, 15(17), 2487-500","doi":"10.1517/14656566.2014.965678","pmid":"25260877","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Key points from this early review:\n\n- GLP-1 is involved in both peripheral and central satiety pathways\n- Clinical trials showed exenatide and liraglutide have weight-lowering potential in non-diabetic obese individuals\n- GLP-1 drugs may prevent diabetes development compared to other weight loss agents\n- Incretin impairment exists in both obesity and diabetes, potentially linking these two conditions\n- At the time of writing (2014), bariatric surgery was the only efficient obesity treatment\n- The review predicted GLP-1-based therapies would play a key role in prevention and treatment of both obesity and diabetes","whyItMatters":"This review was remarkably prescient. Written when GLP-1 drugs were primarily diabetes medications, it correctly predicted their transformation into major obesity treatments and their potential for diabetes prevention. Reading it now provides valuable historical context for the GLP-1 revolution that has since occurred with semaglutide and tirzepatide approvals for obesity.","specificNumbers":"","methodology":"Narrative literature review of PubMed publications through August 2014, using search terms combining GLP-1, GLP-1 receptor agonists, incretins, obesity, and pre-diabetes. The review covered the biological rationale for GLP-1 therapies and summarized clinical trial evidence for their weight-lowering properties.","limitations":"As a 2014 review, it predates the most impactful GLP-1 obesity trials (STEP, SURMOUNT). It covers only exenatide and liraglutide, not newer agents like semaglutide or tirzepatide. The evidence base at the time was limited to relatively small trials in non-diabetic obese populations. The review could not foresee the magnitude of weight loss that higher-dose formulations and dual agonists would achieve."},{"rthcId":"RPEP-02412","title":"Potentiation of cytotoxic chemotherapy by growth hormone-releasing hormone agonists.","authors":"Jaszberenyi, Miklos; Rick, Ferenc G; Popovics, Petra; Block, Norman L; Zarandi, Marta; Cai, Ren-Zhi; Vidaurre, Irving; Szalontay, Luca; Jayakumar, Arumugam R; Schally, Andrew V","year":2014,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 111(2), 781-6","doi":"10.1073/pnas.1322622111","pmid":"24379381","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02413","title":"Dipeptidyl peptidase IV and its inhibitors: therapeutics for type 2 diabetes and what else?","authors":"Juillerat-Jeanneret, Lucienne","year":2014,"journal":"Journal of medicinal chemistry, 57(6), 2197-212","doi":"10.1021/jm400658e","pmid":"24099035","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"DPP-4 is a widely expressed enzyme that clips dipeptides from the N-terminus of peptides containing proline or alanine at position 2. Its most clinically relevant targets are the incretin hormones GLP-1 and GIP, which regulate blood glucose. Several families of DPP-4 inhibitors have been developed, and multiple gliptins are now approved for type 2 diabetes based on their ability to preserve incretin activity and improve glycemic control.\n\nBeyond diabetes, this review highlights that DPP-4 has many other peptide substrates involved in immune regulation, inflammation, and cell signaling — suggesting gliptins could potentially be repurposed for other therapeutic areas.","whyItMatters":"DPP-4 inhibitors were one of the first peptide-based therapeutic strategies to achieve widespread clinical use in diabetes. Understanding how these drugs protect incretins from enzymatic degradation provides a foundation for understanding the newer GLP-1 receptor agonists (like semaglutide and tirzepatide) that took a different approach to the same problem. The review also flags the broader biological significance of DPP-4, which remains relevant as researchers explore incretin biology beyond blood sugar control.","specificNumbers":"","methodology":"This is a Perspective article published in the Journal of Medicinal Chemistry. It reviews the biological functions of DPP-4, the structure-activity relationships of various DPP-4 inhibitor families, their clinical development for type 2 diabetes, and emerging evidence for non-diabetic applications. It synthesizes data from preclinical models and clinical trials.","limitations":"As a review/perspective article, this does not present new experimental data. The discussion of non-diabetic applications is largely based on preclinical evidence and mechanistic reasoning rather than clinical trials. The field has advanced considerably since 2014, and some predictions about future applications may not have panned out."},{"rthcId":"RPEP-02414","title":"Opioid signaling in mast cells regulates injury responses associated with heterotopic ossification.","authors":"Kan, Lixin; Mutso, Amelia A; McGuire, Tammy L; Apkarian, Apkar Vania; Kessler, John A","year":2014,"journal":"Inflammation research : official journal of the European Histamine Research Society ... [et al.], 63(3), 207-15","doi":"10.1007/s00011-013-0690-4","pmid":"24327087","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02415","title":"Short-term aerobic exercise training increases postprandial pancreatic polypeptide but not peptide YY concentrations in obese individuals.","authors":"Kanaley, J A; Heden, T D; Liu, Y; Whaley-Connell, A T; Chockalingam, A; Dellsperger, K C; Fairchild, T J","year":2014,"journal":"International journal of obesity (2005), 38(2), 266-71","doi":"10.1038/ijo.2013.84","pmid":"23736355","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02416","title":"Effect of GLP-1 mimetics on blood pressure and relationship to weight loss and glycemia lowering: results of a systematic meta-analysis and meta-regression.","authors":"Katout, Mohammad; Zhu, Hong; Rutsky, Jessica; Shah, Parthy; Brook, Robert D; Zhong, Jixin; Rajagopalan, Sanjay","year":2014,"journal":"American journal of hypertension, 27(1), 130-9","doi":"10.1093/ajh/hpt196","pmid":"24263424","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02417","title":"Intrarenal ghrelin receptor antagonism prevents high-fat diet-induced hypertension in male rats.","authors":"Kemp, Brandon A; Howell, Nancy L; Gildea, John J; Padia, Shetal H","year":2014,"journal":"Endocrinology, 155(7), 2658-66","doi":"10.1210/en.2013-2177","pmid":"24797629","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02418","title":"Nicotine effects and the endogenous opioid system.","authors":"Kishioka, Shiroh; Kiguchi, Norikazu; Kobayashi, Yuka; Saika, Fumihiro","year":2014,"journal":"Journal of pharmacological sciences, 125(2), 117-24","doi":null,"pmid":"24882143","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02419","title":"Hyperglycemia abolishes meal-induced satiety by a dysregulation of ghrelin and peptide YY3-36 in healthy overweight/obese humans.","authors":"Knudsen, Sine H; Karstoft, Kristian; Solomon, Thomas P J","year":2014,"journal":"American journal of physiology. Endocrinology and metabolism, 306(2), E225-31","doi":"10.1152/ajpendo.00563.2013","pmid":"24302008","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02420","title":"Intranasal oxytocin as strategy for medication-enhanced psychotherapy of PTSD: salience processing and fear inhibition processes.","authors":"Koch, Saskia B J; van Zuiden, Mirjam; Nawijn, Laura; Frijling, Jessie L; Veltman, Dick J; Olff, Miranda","year":2014,"journal":"Psychoneuroendocrinology, 40, 242-56","doi":"10.1016/j.psyneuen.2013.11.018","pmid":"24485496","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02421","title":"Efficacy of peptide anxiolytic selank during modeling of withdrawal syndrome in rats with stable alcoholic motivation.","authors":"Kolik, L G; Nadorova, A V; Kozlovskaya, M M","year":2014,"journal":"Bulletin of experimental biology and medicine, 157(1), 52-5","doi":"10.1007/s10517-014-2490-4","pmid":"24913576","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A single intraperitoneal injection of selank at 0.3 mg/kg eliminated anxiety caused by alcohol withdrawal in rats, as measured by the elevated plus maze and social interaction tests. Selank also prevented the development of mechanical allodynia (pain hypersensitivity) — a common withdrawal symptom. Notably, selank reduced withdrawal symptoms without affecting the rats' ethanol consumption, meaning it treated the withdrawal without changing drinking behavior.","whyItMatters":"Alcohol withdrawal is a dangerous medical condition that can include severe anxiety, pain sensitization, seizures, and even death. Current treatments (primarily benzodiazepines) carry their own addiction risk. Selank — a synthetic peptide anxiolytic derived from the natural immunopeptide tuftsin — showed the ability to address both the anxiety and pain components of withdrawal without sedation or affecting alcohol intake, suggesting it could be a safer alternative.","specificNumbers":"0.3 mg/kg selank (single IP injection) · 48-hour acute withdrawal model · 24 weeks of 10% ethanol exposure · Alcohol-preferring rats (>5.0 g/kg daily intake) · Eliminated anxiety + prevented allodynia","methodology":"Outbred rats were given 10% ethanol as their only fluid source for 24 weeks to establish stable alcohol dependence. Alcohol-preferring animals (consuming >5.0 g/kg/day) were selected. After 48 hours of acute withdrawal, rats received a single intraperitoneal injection of selank (0.3 mg/kg). Anxiety was measured using the elevated plus maze and social interaction tests. Pain sensitivity (mechanical allodynia) was also assessed. A free-choice ethanol/water test measured whether selank affected drinking behavior.","limitations":"This is a rat study with a single dose and single time point — it doesn't address whether selank works with repeated dosing or during prolonged withdrawal. Intraperitoneal injection doesn't reflect typical human administration routes. The study used outbred rats selected for alcohol preference, which may not model all human alcohol dependence patterns. Sample sizes are not specified in the abstract."},{"rthcId":"RPEP-02422","title":"The temporary dynamics of inflammation-related genes expression under tuftsin analog Selank action.","authors":"Kolomin, Timur; Morozova, Marina; Volkova, Anastasiya; Shadrina, Maria; Andreeva, Lyudmila; Slominsky, Petr; Limborska, Svetlana; Myasoedov, Nikolay","year":2014,"journal":"Molecular immunology, 58(1), 50-5","doi":"10.1016/j.molimm.2013.11.002","pmid":"24291245","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02423","title":"Synthesis of substituted pyrimidines as corticotropin releasing factor (CRF) receptor ligands.","authors":"Kuppast, Bhimanna; Spyridaki, Katerina; Liapakis, George; Fahmy, Hesham","year":2014,"journal":"European journal of medicinal chemistry, 78, 1-9","doi":"10.1016/j.ejmech.2014.03.040","pmid":"24675175","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02424","title":"Folate-vinca alkaloid conjugates for cancer therapy: a structure-activity relationship.","authors":"Leamon, Christopher P; Vlahov, Iontcho R; Reddy, Joseph A; Vetzel, Marilynn; Santhapuram, Hari Krishna R; You, Fei; Bloomfield, Alicia; Dorton, Ryan; Nelson, Melissa; Kleindl, Paul; Vaughn, Jeremy F; Westrick, Elaine","year":2014,"journal":"Bioconjugate chemistry, 25(3), 560-8","doi":"10.1021/bc400441s","pmid":"24564229","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02425","title":"Photoreactive stapled peptides to identify and characterize BCL-2 family interaction sites by mass spectrometry.","authors":"Lee, Susan; Braun, Craig R; Bird, Gregory H; Walensky, Loren D","year":2014,"journal":"Methods in enzymology, 544, 25-48","doi":"10.1016/B978-0-12-417158-9.00002-9","pmid":"24974285","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02426","title":"Increased tumor distribution and expression of histidine-rich plasmid polyplexes.","authors":"Leng, Qixin; Chou, Szu-Ting; Scaria, Puthupparampil V; Woodle, Martin C; Mixson, A James","year":2014,"journal":"The journal of gene medicine, 16(9-10), 317-28","doi":"10.1002/jgm.2807","pmid":"25303767","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02427","title":"Bactericidal effect of bovine lactoferrin and synthetic peptide lactoferrin chimera in Streptococcus pneumoniae and the decrease in luxS gene expression by lactoferrin.","authors":"León-Sicairos, Nidia; Angulo-Zamudio, Uriel A; Vidal, Jorge E; López-Torres, Cynthia A; Bolscher, Jan G M; Nazmi, Kamran; Reyes-Cortes, Ruth; Reyes-López, Magda; de la Garza, Mireya; Canizalez-Román, Adrian","year":2014,"journal":"Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine, 27(5), 969-80","doi":"10.1007/s10534-014-9775-y","pmid":"25053107","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02428","title":"Abnormal response to the anorexic effect of GHS-R inhibitors and exenatide in male Snord116 deletion mouse model for Prader-Willi syndrome.","authors":"Lin, Dahe; Wang, Qi; Ran, Haiying; Liu, Kai; Wang, Yao; Wang, Juanjuan; Liu, Yazhen; Chen, Ruichuan; Sun, Yuxiang; Liu, Runzhong; Ding, Feng","year":2014,"journal":"Endocrinology, 155(7), 2355-62","doi":"10.1210/en.2013-2083","pmid":"24735326","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02429","title":"Ghrelin receptor regulates appetite and satiety during aging in mice by regulating meal frequency and portion size but not total food intake.","authors":"Lin, Ligen; Nuotio-Antar, Alli M; Ma, Xiaojun; Liu, Feng; Fiorotto, Marta L; Sun, Yuxiang","year":2014,"journal":"The Journal of nutrition, 144(9), 1349-55","doi":"10.3945/jn.114.191171","pmid":"24991043","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02430","title":"The VGF-derived peptide TLQP62 produces antidepressant-like effects in mice via the BDNF/TrkB/CREB signaling pathway.","authors":"Lin, Peipei; Wang, Chuang; Xu, Bing; Gao, Siyun; Guo, Jiejie; Zhao, Xin; Huang, Huihui; Zhang, Junfang; Chen, Xiaowei; Wang, Qinwen; Zhou, Wenhua","year":2014,"journal":"Pharmacology, biochemistry, and behavior, 120, 140-8","doi":"10.1016/j.pbb.2014.03.003","pmid":"24631486","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02431","title":"Teaghrelins, unique acylated flavonoid tetraglycosides in Chin-shin oolong tea, are putative oral agonists of the ghrelin receptor.","authors":"Lo, Yuan-Hao; Chen, Ying-Jie; Chang, Chi-I; Lin, Yi-Wen; Chen, Chung-Yu; Lee, Maw-Rong; Lee, Viola S Y; Tzen, Jason T C","year":2014,"journal":"Journal of agricultural and food chemistry, 62(22), 5085-91","doi":"10.1021/jf501425m","pmid":"24832927","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02432","title":"Blood pressure-lowering effects of incretin-based diabetes therapies.","authors":"Lovshin, Julie A; Zinman, Bernard","year":2014,"journal":"Canadian journal of diabetes, 38(5), 364-71","doi":"10.1016/j.jcjd.2014.05.001","pmid":"25284699","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02433","title":"Amyloid beta lowering and cognition enhancing effects of ghrelin receptor analog [D-Lys (3)] GHRP-6 in rat model of obesity.","authors":"Madhavadas, Sowmya; Kutty, Bindu M; Subramanian, Sarada","year":2014,"journal":"Indian journal of biochemistry & biophysics, 51(4), 257-62","doi":null,"pmid":"25296496","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02434","title":"Presentation of BMP-2 mimicking peptides in 3D hydrogels directs cell fate commitment in osteoblasts and mesenchymal stem cells.","authors":"Madl, Christopher M; Mehta, Manav; Duda, Georg N; Heilshorn, Sarah C; Mooney, David J","year":2014,"journal":"Biomacromolecules, 15(2), 445-55","doi":"10.1021/bm401726u","pmid":"24400664","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Peptides derived from the knuckle epitope of BMP-2, covalently conjugated to alginate hydrogels, increased alkaline phosphatase activity in osteoblasts when presented from both 2D surfaces and 3D hydrogels. In 3D hydrogels, the peptides initiated Smad signaling (the canonical BMP pathway), upregulated osteopontin production, and increased mineral deposition in murine mesenchymal stem cells. The peptides were attached via carbodiimide or sulfhydryl coupling strategies, both confirmed by NMR spectroscopy and quantified by fluorescent labeling.","whyItMatters":"BMP-2 is clinically used to promote bone healing (e.g., spinal fusion), but its use is associated with significant side effects including bone overgrowth, inflammation, and pain in surrounding tissues. A scaffold that presents BMP-mimicking peptides locally — keeping the bone-forming signal exactly where it's needed — could provide the benefits of BMP-2 without the off-target complications. This is especially important for stem cell-based bone regeneration therapies.","specificNumbers":"","methodology":"BMP-2 mimicking peptides were synthesized using solid-phase Fmoc peptide synthesis and conjugated to alginate hydrogels using two different chemical strategies (carbodiimide and sulfhydryl coupling). Conjugation was verified by 1H NMR spectroscopy. Testing used clonally derived murine osteoblasts (2D and 3D) and mesenchymal stem cells (3D). Readouts included alkaline phosphatase activity, Smad signaling activation, osteopontin production, and mineral deposition.","limitations":"All experiments were performed in vitro with murine cells — no in vivo bone formation data were presented. The alginate hydrogels used may not have the mechanical properties needed for load-bearing bone applications. The study tested only one BMP-2 epitope (knuckle region) and did not compare peptide efficacy to full-length BMP-2 protein. Long-term stem cell behavior and potential differentiation into unwanted cell types were not assessed."},{"rthcId":"RPEP-02435","title":"The effects of tesamorelin on phosphocreatine recovery in obese subjects with reduced GH.","authors":"Makimura, Hideo; Murphy, Caitlin A; Feldpausch, Meghan N; Grinspoon, Steven K","year":2014,"journal":"The Journal of clinical endocrinology and metabolism, 99(1), 338-43","doi":"10.1210/jc.2013-3436","pmid":"24178787","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"After 12 months, tesamorelin treatment significantly increased IGF-I compared to placebo (change: +102.9 vs +22.8 μg/L; P = 0.02). The key finding was the relationship between IGF-I increases and mitochondrial function:\n\n- Overall correlation between IGF-I increase and phosphocreatine recovery improvement (ViPCr): R = 0.56, P = 0.01\n- In tesamorelin-treated subjects only: R = 0.71, P = 0.03 (strong correlation)\n- The association remained significant after controlling for age, sex, race, ethnicity, body composition, and insulin sensitivity (all P < 0.05)\n\nPhosphocreatine recovery rate is a validated marker of mitochondrial oxidative capacity, suggesting tesamorelin improves mitochondrial function through IGF-I elevation.","whyItMatters":"Mitochondrial dysfunction is implicated in aging, obesity, diabetes, and many chronic diseases. This study provides the first evidence from a randomized trial that boosting the GH/IGF-I axis with a GHRH peptide analog can improve mitochondrial function in humans. Since tesamorelin is FDA-approved (for HIV lipodystrophy), this finding suggests a potential new application for an existing peptide drug and strengthens the scientific case for growth hormone-releasing peptides in metabolic health.","specificNumbers":"","methodology":"Double-blind, randomized, placebo-controlled trial over 12 months. 39 obese men and women with reduced GH secretion (confirmed by GHRH-arginine stimulation testing) were randomized to tesamorelin or placebo. Mitochondrial function was assessed using 31P magnetic resonance spectroscopy to measure phosphocreatine recovery after submaximal exercise — a gold-standard noninvasive measure of muscle mitochondrial capacity. IGF-I and body composition were measured at baseline and 12 months.","limitations":"Relatively small sample size (39 participants) limits statistical power for subgroup analyses. The correlation between IGF-I and PCr recovery, while strong, doesn't prove causation — other effects of tesamorelin could contribute. Only phosphocreatine recovery was used as a mitochondrial marker; direct mitochondrial assessments (biopsy, respiration) were not performed. The study population (obese with reduced GH) is specific and results may not generalize to GH-sufficient individuals. The clinical significance of the observed mitochondrial improvements for patient outcomes is unknown."},{"rthcId":"RPEP-02436","title":"Advancing drug therapy for brain tumours: a current review of the pro-inflammatory peptide Substance P and its antagonists as anti-cancer agents.","authors":"Mander, Kimberley; Harford-Wright, Elizabeth; Lewis, Kate M; Vink, Robert","year":2014,"journal":"Recent patents on CNS drug discovery, 9(2), 110-21","doi":null,"pmid":"25386916","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02437","title":"Immunohistochemical mapping of pro-opiomelanocortin- and pro-dynorphin-derived peptides in the alpaca (Lama pacos) diencephalon.","authors":"Manso, B; Sánchez, M L; Medina, L E; Aguilar, L A; Díaz-Cabiale, Z; Narváez, J A; Coveñas, R","year":2014,"journal":"Journal of chemical neuroanatomy, 59-60, 36-50","doi":"10.1016/j.jchemneu.2014.06.001","pmid":"24956196","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02438","title":"The cardiovascular action of hexarelin.","authors":"Mao, Yuanjie; Tokudome, Takeshi; Kishimoto, Ichiro","year":2014,"journal":"Journal of geriatric cardiology : JGC, 11(3), 253-8","doi":"10.11909/j.issn.1671-5411.2014.03.007","pmid":"25278975","tags":[],"studyType":"review","evidenceStrength":"low-moderate","keyFinding":"Hexarelin, a synthetic growth hormone-releasing peptide, has direct cardiovascular effects beyond growth hormone release. It activates both the ghrelin receptor (GHSR) in the brain and a specific cardiac receptor called CD36, which mediates its cardioprotective effects. Compared to the natural hormone ghrelin, hexarelin is more chemically stable and functionally more potent.\n\nThe review summarizes evidence that hexarelin can protect the heart through direct actions on cardiac and vascular tissue, independent of its growth hormone-stimulating properties.","whyItMatters":"Growth hormone-releasing peptides have been studied primarily for their hormonal effects, but hexarelin's direct cardiac actions through the CD36 receptor represent a distinct therapeutic mechanism. If these cardioprotective effects can be harnessed clinically, hexarelin could serve as a targeted cardiac peptide therapy, particularly for conditions where growth hormone effects are unwanted.","specificNumbers":"2 receptors: GHSR (brain) and CD36 (cardiac) · More stable than ghrelin · More potent than ghrelin · Direct cardiac and vascular actions","methodology":"Concise narrative review summarizing preclinical and mechanistic evidence for hexarelin's cardiovascular actions, including receptor binding studies, cardiac protection experiments, and comparisons with natural ghrelin.","limitations":"As a brief narrative review, it does not comprehensively evaluate all available evidence or assess study quality. Most evidence is preclinical. Clinical cardiovascular studies of hexarelin are limited. The review is from 2014 and newer evidence may have emerged."},{"rthcId":"RPEP-02439","title":"Serum levels of vasoactive intestinal peptide as a prognostic marker in early arthritis.","authors":"Martínez, Carmen; Ortiz, Ana M; Juarranz, Yasmina; Lamana, Amalia; Seoane, Iria V; Leceta, Javier; García-Vicuña, Rosario; Gomariz, Rosa P; González-Álvaro, Isidoro","year":2014,"journal":"PloS one, 9(1), e85248","doi":"10.1371/journal.pone.0085248","pmid":"24409325","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02440","title":"The central nervous system sites mediating the orexigenic actions of ghrelin.","authors":"Mason, B L; Wang, Q; Zigman, J M","year":2014,"journal":"Annual review of physiology, 76, 519-33","doi":"10.1146/annurev-physiol-021113-170310","pmid":"24111557","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02441","title":"Identification, optimization, and pharmacology of acylurea GHS-R1a inverse agonists.","authors":"McCoull, William; Barton, Peter; Brown, Alastair J H; Bowker, Suzanne S; Cameron, Jennifer; Clarke, David S; Davies, Robert D M; Dossetter, Alexander G; Ertan, Anne; Fenwick, Mark; Green, Clive; Holmes, Jane L; Martin, Nathaniel; Masters, David; Moore, Jane E; Newcombe, Nicholas J; Newton, Claire; Pointon, Helen; Robb, Graeme R; Sheldon, Christopher; Stokes, Stephen; Morgan, David","year":2014,"journal":"Journal of medicinal chemistry, 57(14), 6128-40","doi":"10.1021/jm500610n","pmid":"24967667","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02442","title":"Ghrelin receptor (GHS-R1a) and its constitutive activity in somatotroph adenomas: a new co-targeting therapy using GHS-R1a inverse agonists and somatostatin analogs.","authors":"Mear, Yves; Blanchard, Marie-Pierre; Defilles, Céline; Brue, Thierry; Figarella-Branger, Dominique; Graillon, Thomas; Manavela, Marcos; Barlier, Anne; Enjalbert, Alain; Thirion, Sylvie","year":2014,"journal":"The Journal of clinical endocrinology and metabolism, 99(12), E2463-71","doi":"10.1210/jc.2014-2753","pmid":"25272306","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02443","title":"A ghrelin-growth hormone axis drives stress-induced vulnerability to enhanced fear.","authors":"Meyer, R M; Burgos-Robles, A; Liu, E; Correia, S S; Goosens, K A","year":2014,"journal":"Molecular psychiatry, 19(12), 1284-94","doi":"10.1038/mp.2013.135","pmid":"24126924","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The peptide hormone ghrelin drives stress-induced vulnerability to enhanced fear learning through a novel pathway independent of the classical HPA stress axis. Stress-related increases in circulating ghrelin are both necessary and sufficient for exacerbated fear learning, acting through ghrelin receptors in the amygdala. Ghrelin's fear-enhancing effects require growth hormone (GH) in the amygdala — GH was upregulated after chronic stress, its release was enhanced by ghrelin receptor stimulation, and blocking GH receptors prevented ghrelin's fear-enhancing effects. Critically, ghrelin receptor antagonism during stress blocked enhanced fear without affecting corticosterone levels, confirming this is a separate stress response pathway.","whyItMatters":"PTSD and stress-related disorders have long been linked to the HPA axis (cortisol/corticosterone), but treatments targeting this system have had limited success. This study reveals ghrelin — a peptide better known for regulating hunger — as a mediator of a completely separate stress response branch that directly enhances fear memories in the brain's fear center. This opens new therapeutic targets for PTSD that don't involve the traditional stress hormone pathway.","specificNumbers":"Ghrelin receptor agonist enhanced fear memory · ghrelin antagonism blocked stress-enhanced fear · GH upregulated in amygdala after chronic stress · effects independent of CRF and corticosterone","methodology":"Researchers used a rodent PTSD model where rats repeatedly exposed to stressors develop heightened fear learning via auditory Pavlovian fear conditioning. They used systemic and intraamygdala ghrelin receptor agonist/antagonist administration, virus-mediated overexpression of GH and GH receptor antagonist in the amygdala, and measured circulating ghrelin, corticosterone, CRF, and amygdala GH protein levels.","limitations":"This is a rodent study, and the ghrelin-GH-fear pathway may not translate identically to humans. The PTSD model, while well-established, is a simplified representation of the complex human disorder. The study focused on fear learning rather than other PTSD features like avoidance or hyperarousal. Ghrelin manipulation could affect feeding behavior and metabolism, which may confound behavioral observations."},{"rthcId":"RPEP-02444","title":"Stress-induced dendritic internalization and nuclear translocation of the neurokinin-3 (NK3) receptor in vasopressinergic profiles of the rat paraventricular nucleus of the hypothalamus.","authors":"Miklos, Zachary; Flynn, Francis W; Lessard, Andrée","year":2014,"journal":"Brain research, 1590, 31-44","doi":"10.1016/j.brainres.2014.09.043","pmid":"25281803","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02445","title":"Healing of surgical castration wounds: a description and an evaluation of flunixin.","authors":"Mintline, E M; Varga, A; Banuelos, J; Walker, K A; Hoar, B; Drake, Daniel; Weary, D M; Coetzee, J F; Stock, M L; Tucker, C B","year":2014,"journal":"Journal of animal science, 92(12), 5659-65","doi":"10.2527/jas.2014-7885","pmid":"25367511","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02446","title":"Aerosolized oxytocin increases cerebrospinal fluid oxytocin in rhesus macaques.","authors":"Modi, Meera E; Connor-Stroud, Fawn; Landgraf, Rainer; Young, Larry J; Parr, Lisa A","year":2014,"journal":"Psychoneuroendocrinology, 45, 49-57","doi":"10.1016/j.psyneuen.2014.02.011","pmid":"24845176","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02447","title":"Ghrelin: from discovery to cancer cachexia therapy.","authors":"Molfino, Alessio; Formiconi, Alessandra; Rossi Fanelli, Filippo; Muscaritoli, Maurizio","year":2014,"journal":"Current opinion in clinical nutrition and metabolic care, 17(5), 471-6","doi":"10.1097/MCO.0000000000000075","pmid":"24905862","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02448","title":"Rapid total synthesis of DARPin pE59 and barnase.","authors":"Mong, Surin K; Vinogradov, Alexander A; Simon, Mark D; Pentelute, Bradley L","year":2014,"journal":"Chembiochem : a European journal of chemical biology, 15(5), 721-33","doi":"10.1002/cbic.201300797","pmid":"24616257","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02449","title":"Body weight loss, reduced urge for palatable food and increased release of GLP-1 through daily supplementation with green-plant membranes for three months in overweight women.","authors":"Montelius, Caroline; Erlandsson, Daniel; Vitija, Egzona; Stenblom, Eva-Lena; Egecioglu, Emil; Erlanson-Albertsson, Charlotte","year":2014,"journal":"Appetite, 81, 295-304","doi":"10.1016/j.appet.2014.06.101","pmid":"24993695","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Over 12 weeks, the green-plant membrane group lost significantly more weight than placebo (5.0 ± 2.3 kg vs 3.5 ± 2.3 kg, p < 0.01). The supplement also significantly reduced total cholesterol (p < 0.01) and LDL cholesterol (p < 0.05) compared to control.\n\nSingle-meal tests on days 1 and 90 showed the supplement group had increased postprandial GLP-1 release and decreased urge for sweet and chocolate on both occasions. This effect was consistent from the first day through the end of the study.\n\nWaist circumference, body fat, and leptin decreased in both groups over the study period, but there were no significant between-group differences for these measures. The authors propose that increased GLP-1 release may be the primary mechanism behind the weight loss and appetite effects.","whyItMatters":"This study connects a natural dietary supplement to GLP-1 release — the same peptide pathway that GLP-1 receptor agonist drugs (like semaglutide) target for weight loss. Finding a food-based approach that naturally increases GLP-1 secretion could offer a complementary or alternative strategy for weight management, particularly for people who cannot access or tolerate pharmaceutical GLP-1 therapies.","specificNumbers":"","methodology":"This was a single-blind, placebo-controlled randomized trial. 38 overweight women (BMI 25-33 kg/m², ages 40-65) were randomized to receive either 5g of green-plant membranes or placebo once daily before breakfast for 12 weeks. All participants were instructed to follow a three-meal pattern with no snacking and to increase physical activity. Body weight was measured every 3 weeks, along with blood glucose and lipid parameters. On days 1 and 90, standardized breakfast tests measured plasma glucose, insulin, and GLP-1, plus subjective hunger, satiety, and food cravings via visual analogue scales.","limitations":"The sample size of 38 women is small and limits statistical power. The study was single-blind (not double-blind), which could introduce observer bias. Only women aged 40-65 were included, so results may not generalize to men or other age groups. All participants were also instructed to follow dietary and exercise guidelines, making it difficult to isolate the supplement's independent effect. The 12-week duration doesn't address long-term weight maintenance. The specific GLP-1 increase was not quantified in the abstract."},{"rthcId":"RPEP-02450","title":"The negatively charged regions of lactoferrin binding protein B, an adaptation against anti-microbial peptides.","authors":"Morgenthau, Ari; Beddek, Amanda; Schryvers, Anthony B","year":2014,"journal":"PloS one, 9(1), e86243","doi":"10.1371/journal.pone.0086243","pmid":"24465982","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The negatively charged regions of lactoferrin binding protein B (LbpB) in Neisseria meningitidis are essential for protecting the bacteria against lactoferricin, a cationic antimicrobial peptide. Removing these negatively charged regions eliminated LbpB's protective effect while maintaining the protein's structural stability. LbpB provided greater protection against lactoferricin than the bacterial polysaccharide capsule, suggesting it is a major defense mechanism against host antimicrobial peptides. The selective release of LbpB from the cell surface by the autotransporter NalP may serve primarily for immune evasion rather than iron acquisition.","whyItMatters":"Understanding how pathogenic bacteria defend themselves against the body's natural antimicrobial peptides is crucial for developing new anti-infective strategies. This study reveals that LbpB acts as a shield specifically neutralizing cationic antimicrobial peptides like lactoferricin, which could be exploited to make bacteria more vulnerable to these natural immune defenses.","specificNumbers":"LbpB protection > capsule protection · negatively charged regions conserved across all species except Moraxella bovis · C-terminal lobe location · NalP-mediated release reduces in vitro protection","methodology":"Laboratory study using Neisseria meningitidis. Researchers engineered LbpB variants with negatively charged regions removed and tested bacterial survival against lactoferricin in killing assays. The role of NalP-mediated LbpB release and polysaccharide capsule protection were also assessed. Protein stability was verified to ensure mutations didn't simply destroy the protein.","limitations":"In vitro killing assays may not fully replicate in vivo conditions where NalP release and capsule dynamics differ. The study focused on lactoferricin specifically and did not test other antimicrobial peptides. The proposed in vivo functions are inferred but not directly demonstrated in animal infection models."},{"rthcId":"RPEP-02451","title":"The specificity of protection against cationic antimicrobial peptides by lactoferrin binding protein B.","authors":"Morgenthau, Ari; Partha, Sarathy K; Adamiak, Paul; Schryvers, Anthony B","year":2014,"journal":"Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine, 27(5), 923-33","doi":"10.1007/s10534-014-9767-y","pmid":"25038734","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02452","title":"Whole body, regional fat accumulation, and appetite-related hormonal response after hypoxic training.","authors":"Morishima, Takuma; Kurihara, Toshiyuki; Hamaoka, Takafumi; Goto, Kazushige","year":2014,"journal":"Clinical physiology and functional imaging, 34(2), 90-7","doi":"10.1111/cpf.12069","pmid":"23879294","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02453","title":"Switching brain serotonin with oxytocin.","authors":"Mottolese, Raphaelle; Redouté, Jérôme; Costes, Nicolas; Le Bars, Didier; Sirigu, Angela","year":2014,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 111(23), 8637-42","doi":"10.1073/pnas.1319810111","pmid":"24912179","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02454","title":"Involvement of substance P and the NK-1 receptor in human pathology.","authors":"Muñoz, Miguel; Coveñas, Rafael","year":2014,"journal":"Amino acids, 46(7), 1727-50","doi":"10.1007/s00726-014-1736-9","pmid":"24705689","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02455","title":"Growth hormone-releasing hormone antagonists abolish the transactivation of human epidermal growth factor receptors in advanced prostate cancer models.","authors":"Muñoz-Moreno, Laura; Arenas, M Isabel; Carmena, M José; Schally, Andrew V; Prieto, Juan C; Bajo, Ana M","year":2014,"journal":"Investigational new drugs, 32(5), 871-82","doi":"10.1007/s10637-014-0131-4","pmid":"25000999","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In PC3 androgen-independent prostate cancer cells and nude mouse xenografts:\n\n- GHRH stimulated expression and activation of both EGFR and HER2\n- GHRH caused rapid ligand-independent HER activation via cAMP/PKA and Src pathways\n- GHRH also caused slow ligand-dependent HER activation via ADAM-mediated extracellular pathway\n- GHRH antagonists JMR-132 and JV-1-38 abrogated GHRH-stimulated responses in vitro\n- EGF reciprocally increased GHRH and GHRH receptor mRNA — bidirectional cross-talk\n- In vivo: JV-1-38 inhibited tumor growth with substantial reduction in EGFR/HER2 mRNA and protein\n- JV-1-38 significantly decreased phosphorylated Src levels in tumors","whyItMatters":"Advanced prostate cancer that no longer responds to hormone therapy has limited treatment options. This study reveals a previously unknown connection between the peptide hormone GHRH and cancer-driving growth factor receptors, and shows that GHRH antagonist peptides can block this connection. This opens a new therapeutic strategy for one of the most aggressive forms of prostate cancer.","specificNumbers":"","methodology":"In vitro studies used PC3 human androgen-independent prostate cancer cells. GHRH effects on EGFR and HER2 expression and activation were assessed by time-course studies. GHRH antagonists JMR-132 and JV-1-38 were tested for receptor blocking. Signaling pathways were dissected using PKA and Src inhibitors. In vivo, nude mice bearing PC3 xenografts were treated with JV-1-38, and tumors were analyzed for EGFR, HER2, and Src expression.","limitations":"The in vitro studies used a single cell line (PC3), which may not represent the diversity of prostate cancers. The in vivo xenograft model uses immunodeficient mice and may not fully reflect human tumor biology and immune interactions. The GHRH antagonists' effects on normal tissues and side effects were not assessed. The study focused on androgen-independent cancer; effects in earlier-stage prostate cancer are unknown."},{"rthcId":"RPEP-02456","title":"Oxytocin modulates female sociosexual behavior through a specific class of prefrontal cortical interneurons.","authors":"Nakajima, Miho; Görlich, Andreas; Heintz, Nathaniel","year":2014,"journal":"Cell, 159(2), 295-305","doi":"10.1016/j.cell.2014.09.020","pmid":"25303526","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02457","title":"The TRPA1 channel in inflammatory and neuropathic pain and migraine.","authors":"Nassini, Romina; Materazzi, Serena; Benemei, Silvia; Geppetti, Pierangelo","year":2014,"journal":"Reviews of physiology, biochemistry and pharmacology, 167, 1-43","doi":"10.1007/112_2014_18","pmid":"24668446","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02458","title":"Appetite control and biomarkers of satiety with vegetarian (soy) and meat-based high-protein diets for weight loss in obese men: a randomized crossover trial.","authors":"Neacsu, Madalina; Fyfe, Claire; Horgan, Graham; Johnstone, Alexandra M","year":2014,"journal":"The American journal of clinical nutrition, 100(2), 548-58","doi":"10.3945/ajcn.113.077503","pmid":"24944057","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02459","title":"Pro-substance p for evaluation of risk in acute myocardial infarction.","authors":"Ng, Leong L; Sandhu, Jatinderpal K; Narayan, Hafid; Quinn, Paulene A; Squire, Iain B; Davies, Joan E; Struck, Joachim; Bergmann, Andreas; Maisel, Alan; Jones, Donald J L","year":2014,"journal":"Journal of the American College of Cardiology, 64(16), 1698-707","doi":"10.1016/j.jacc.2014.05.074","pmid":"25323258","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02460","title":"Hepatitis B and D viruses exploit sodium taurocholate co-transporting polypeptide for species-specific entry into hepatocytes.","authors":"Ni, Yi; Lempp, Florian A; Mehrle, Stefan; Nkongolo, Shirin; Kaufman, Christina; Fälth, Maria; Stindt, Jan; Königer, Christian; Nassal, Michael; Kubitz, Ralf; Sültmann, Holger; Urban, Stephan","year":2014,"journal":"Gastroenterology, 146(4), 1070-83","doi":"10.1053/j.gastro.2013.12.024","pmid":"24361467","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02461","title":"The milk-derived peptides Val-Pro-Pro and Ile-Pro-Pro attenuate arterial dysfunction in L-NAME-treated rats.","authors":"Nonaka, Atsuko; Nakamura, Teppei; Hirota, Tatsuhiko; Matsushita, Akiko; Asakura, Masanori; Ohki, Kohji; Kitakaze, Masafumi","year":2014,"journal":"Hypertension research : official journal of the Japanese Society of Hypertension, 37(8), 703-7","doi":"10.1038/hr.2014.72","pmid":"24694646","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02462","title":"Susceptibility of milk protein-derived peptides to dipeptidyl peptidase IV (DPP-IV) hydrolysis.","authors":"Nongonierma, Alice B; FitzGerald, Richard J","year":2014,"journal":"Food chemistry, 145, 845-52","doi":"10.1016/j.foodchem.2013.08.097","pmid":"24128555","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02463","title":"Disulfide-rich macrocyclic peptides as templates in drug design.","authors":"Northfield, Susan E; Wang, Conan K; Schroeder, Christina I; Durek, Thomas; Kan, Meng-Wei; Swedberg, Joakim E; Craik, David J","year":2014,"journal":"European journal of medicinal chemistry, 77, 248-57","doi":"10.1016/j.ejmech.2014.03.011","pmid":"24650712","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review describes how disulfide-rich head-to-tail cyclic peptides possess exceptional thermal, chemical, and enzymatic stability due to their highly constrained structures. These naturally occurring peptide scaffolds can be utilized in two key ways for drug design:\n\n1. Epitope grafting — inserting pharmaceutically active sequences into the stable cyclic framework to give them enhanced stability and bioavailability\n2. Engineering — modifying the scaffold itself to increase selectivity and bioactivity for specific targets\n\nThese approaches open possibilities for addressing 'difficult' pharmaceutical targets that are not easily druggable by conventional small molecules or antibodies, including intracellular protein-protein interactions.","whyItMatters":"A major challenge in drug development is that many disease-causing proteins are considered 'undruggable' because small molecule drugs are too simple to bind them effectively, while antibodies are too large to reach intracellular targets. Cyclic disulfide-rich peptides bridge this gap — they are large and structured enough to bind complex protein surfaces, yet small and stable enough to potentially survive oral delivery and enter cells. This review outlines a roadmap for using nature's own molecular engineering to solve this problem.","specificNumbers":"","methodology":"This is a review article surveying current trends in peptide-based pharmaceuticals, with a focus on naturally occurring cyclic disulfide-rich peptide scaffolds. The authors describe the structural and pharmaceutical properties of these scaffolds and review grafting and engineering strategies used to create drug candidates.","limitations":"As a review from 2014, it captures the state of the field at that time and may not reflect more recent advances in cyclic peptide synthesis, delivery, and clinical development. The review focuses on the theoretical promise of these scaffolds, and the abstract does not detail specific clinical successes or failures. The actual translation of grafted cyclic peptides into approved drugs remains an ongoing challenge. Oral bioavailability and cell permeability, while theoretically improved, have been difficult to achieve consistently in practice."},{"rthcId":"RPEP-02464","title":"Biogenesis of D-amino acid containing peptides/proteins: where, when and how?","authors":"Ollivaux, Céline; Soyez, Daniel; Toullec, Jean-Yves","year":2014,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 20(8), 595-612","doi":"10.1002/psc.2637","pmid":"24895293","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02465","title":"Intimate associations between the endogenous opiate systems and the growth hormone-releasing hormone system in the human hypothalamus.","authors":"Olsen, J; Peroski, M; Kiczek, M; Grignol, G; Merchenthaler, I; Dudas, B","year":2014,"journal":"Neuroscience, 258, 238-45","doi":"10.1016/j.neuroscience.2013.11.011","pmid":"24239719","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02466","title":"Tachykinin: recent developments and novel roles in health and disease.","authors":"Onaga, Takenori","year":2014,"journal":"Biomolecular concepts, 5(3), 225-43","doi":"10.1515/bmc-2014-0008","pmid":"25372755","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review highlights several novel roles for tachykinin peptides discovered in the preceding five years:\n\n1. Neurokinin B (NKB) signaling in the hypothalamus plays a crucial role in regulating gonadotropin hormone secretion and puberty onset — mutations in NKB or its receptor cause failure to enter puberty.\n\n2. Tachykinins have newly identified roles in hematopoiesis (blood cell formation) and venous thromboembolism (blood clotting in veins).\n\n3. Molecular studies revealed prophylactic activities of tachykinins against neurogenic movement disorders based on their molecular structure.\n\n4. Novel connections between substance P and tendinopathy (tendon disease) and taste perception have been clarified.","whyItMatters":"Tachykinin peptides are found throughout the body and influence a wide range of biological processes. Understanding their newly discovered roles could lead to new therapeutic targets for conditions ranging from infertility and delayed puberty to blood disorders and neurological diseases. Drug developers have already targeted tachykinin receptors for pain management, and these new roles expand the potential applications considerably.","specificNumbers":"","methodology":"This is a narrative review article summarizing research on tachykinin peptides published worldwide in the approximately 5 years preceding the review (roughly 2009-2014). It covers studies on nociception, inflammation, hematopoiesis, gonadotropin secretion, and central nervous system diseases.","limitations":"As a narrative review rather than a systematic review, the selection of studies may reflect author bias. The review primarily covers a 5-year window, so earlier foundational work receives less attention. Some of the novel roles described (e.g., in hematopoiesis and thromboembolism) were relatively early findings at the time and may not have been fully validated by subsequent research."},{"rthcId":"RPEP-02467","title":"In vitro transport and satiety of a beta-lactoglobulin dipeptide and beta-casomorphin-7 and its metabolites.","authors":"Osborne, Simone; Chen, Wei; Addepalli, Rama; Colgrave, Michelle; Singh, Tanoj; Tran, Cuong; Day, Li","year":2014,"journal":"Food & function, 5(11), 2706-18","doi":"10.1039/c4fo00164h","pmid":"24892772","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02468","title":"Alcohol-induced changes in opioid peptide levels in adolescent rats are dependent on housing conditions.","authors":"Palm, Sara; Nylander, Ingrid","year":2014,"journal":"Alcoholism, clinical and experimental research, 38(12), 2978-87","doi":"10.1111/acer.12586","pmid":"25515651","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02469","title":"Propylene cross-bridged macrocyclic bifunctional chelator: a new design for facile bioconjugation and robust (64)Cu complex stability.","authors":"Pandya, Darpan N; Bhatt, Nikunj; An, Gwang Il; Ha, Yeong Su; Soni, Nisarg; Lee, Hochun; Lee, Yong Jin; Kim, Jung Young; Lee, Woonghee; Ahn, Heesu; Yoo, Jeongsoo","year":2014,"journal":"Journal of medicinal chemistry, 57(17), 7234-43","doi":"10.1021/jm500348z","pmid":"25137619","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02470","title":"Unstimulated and glucose-stimulated ghrelin in depressed patients and controls.","authors":"Paslakis, Georgios; Westphal, Sabine; Hamann, Bettina; Gilles, Maria; Lederbogen, Florian; Deuschle, Michael","year":2014,"journal":"Journal of psychopharmacology (Oxford, England), 28(6), 582-6","doi":"10.1177/0269881114527655","pmid":"24671339","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02471","title":"Coiled coil peptides and polymer-peptide conjugates: synthesis, self-assembly, characterization and potential in drug delivery systems.","authors":"Pechar, Michal; Pola, Robert; Laga, Richard; Braunová, Alena; Filippov, Sergey K; Bogomolova, Anna; Bednárová, Lucie; Vaněk, Ondřej; Ulbrich, Karel","year":2014,"journal":"Biomacromolecules, 15(7), 2590-9","doi":"10.1021/bm500436p","pmid":"24857680","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02472","title":"Schizophrenia and alcohol dependence: diverse clinical effects of oxytocin and their evolutionary origins.","authors":"Pedersen, Cort A","year":2014,"journal":"Brain research, 1580, 102-23","doi":"10.1016/j.brainres.2014.01.050","pmid":"24508579","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02473","title":"Localisation and activation of the neurokinin 1 receptor in the enteric nervous system of the mouse distal colon.","authors":"Pelayo, Juan-Carlos; Veldhuis, Nicholas A; Eriksson, Emily M; Bunnett, Nigel W; Poole, Daniel P","year":2014,"journal":"Cell and tissue research, 356(2), 319-32","doi":"10.1007/s00441-014-1822-z","pmid":"24728885","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02474","title":"Anamorelin HCl (ONO-7643), a novel ghrelin receptor agonist, for the treatment of cancer anorexia-cachexia syndrome: preclinical profile.","authors":"Pietra, Claudio; Takeda, Yasuhiro; Tazawa-Ogata, Naoko; Minami, Masashi; Yuanfeng, Xia; Duus, Elizabeth Manning; Northrup, Robert","year":2014,"journal":"Journal of cachexia, sarcopenia and muscle, 5(4), 329-37","doi":"10.1007/s13539-014-0159-5","pmid":"25267366","tags":[],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Anamorelin (ANAM) is a potent, orally active ghrelin receptor agonist that significantly increased food intake, body weight, and growth hormone levels in rats at doses of 3, 10, and 30 mg/kg over 6 days. The effects were dose-dependent, with GH increases reaching significance at 10 and 30 mg/kg.\n\nIn pigs, both single-dose (3.5 mg/kg) and continuous dosing (1 mg/kg/day) increased growth hormone and IGF-1 levels. In vitro, ANAM showed strong binding affinity and agonist activity at the ghrelin receptor and stimulated GH release from rat pituitary cells. These results established ANAM as a highly specific ghrelin receptor agonist with appetite-stimulating and anabolic properties.","whyItMatters":"Cancer cachexia — the severe muscle wasting and weight loss seen in many cancer patients — kills an estimated 20% of cancer patients and has no widely effective treatment. An oral ghrelin agonist that can increase appetite, body weight, and growth hormone levels could address this unmet need. Anamorelin's oral bioavailability is particularly important, since cachexia patients often struggle with injections.","specificNumbers":"3, 10, 30 mg/kg doses in rats · 6-day oral dosing · dose-dependent food intake and BW increases · 3.5 mg/kg single dose and 1 mg/kg/day continuous in pigs · GH + IGF-1 increases confirmed","methodology":"In vitro: binding assays and fluorescent imaging plate reader assays in HEK293 and BHK cells to measure ghrelin receptor affinity and agonist activity. GH release was measured in rat pituitary cells. In vivo: rats received oral ANAM at 3, 10, or 30 mg/kg daily for 6 days to track food intake and body weight, with single doses to assess GH response. Pigs received single or continuous ANAM doses to evaluate GH and IGF-1 responses.","limitations":"This is a preclinical pharmacology study in rats and pigs — the results describe the drug's profile before human trials. Cancer cachexia models were not used; the animals were healthy, so the appetite and weight effects may differ in disease states. Long-term safety and efficacy in cancer patients require clinical trial data."},{"rthcId":"RPEP-02475","title":"Effect of ghrelin receptor agonist and antagonist on the activity of arcuate nucleus tyrosine hydroxylase containing neurons in C57BL/6 male mice exposed to normal or high fat diet.","authors":"Pirnik, Z; Majercikova, Z; Holubova, M; Pirnik, R; Zelezna, B; Maletinska, L; Kiss, A","year":2014,"journal":"Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 65(4), 477-86","doi":null,"pmid":"25179080","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02476","title":"Immunomodulatory effects of endogenous and synthetic peptides activating opioid receptors.","authors":"Pomorska, Dorota K; Gach, Katarzyna; Janecka, Anna","year":2014,"journal":"Mini reviews in medicinal chemistry, 14(14), 1148-55","doi":null,"pmid":"25553430","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02477","title":"Firefly luciferase inhibitor-conjugated peptide quenches bioluminescence: a versatile tool for real time monitoring cellular uptake of biomolecules.","authors":"Poutiainen, Pekka K; Rönkkö, Teemu; Hinkkanen, Ari E; Palvimo, Jorma J; Närvänen, Ale; Turhanen, Petri; Laatikainen, Reino; Weisell, Janne; Pulkkinen, Juha T","year":2014,"journal":"Bioconjugate chemistry, 25(1), 4-10","doi":"10.1021/bc4003713","pmid":"24341748","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02478","title":"Oral supplementation of specific collagen peptides has beneficial effects on human skin physiology: a double-blind, placebo-controlled study.","authors":"Proksch, E; Segger, D; Degwert, J; Schunck, M; Zague, V; Oesser, S","year":2014,"journal":"Skin pharmacology and physiology, 27(1), 47-55","doi":"10.1159/000351376","pmid":"23949208","tags":["collagen-peptides"],"studyType":"Randomized Controlled Trial","evidenceStrength":"moderate","keyFinding":"Oral supplementation with specific collagen peptides (2.5 g or 5.0 g daily for 8 weeks) significantly improved skin elasticity compared to placebo in women aged 35–55. The improvement was statistically significant in both dosage groups, and the effect persisted even 4 weeks after supplementation ended — particularly in older women.\n\nSkin moisture and transepidermal water loss showed positive trends in subgroup analyses but did not reach statistical significance overall. No side effects were reported throughout the study.","whyItMatters":"This is one of the earlier well-designed RCTs demonstrating that orally ingested collagen peptides can measurably change skin properties. The fact that improvements in elasticity persisted after supplementation stopped suggests the peptides may stimulate longer-term changes in the skin's collagen matrix rather than just providing a temporary effect.","specificNumbers":"n=69 · 2.5 g and 5.0 g daily doses · 8-week treatment · significant elasticity improvement vs placebo · effect persisted 4 weeks post-treatment","methodology":"Double-blind, placebo-controlled trial. 69 women aged 35–55 were randomized into three groups of 23: 2.5 g collagen hydrolysate, 5.0 g collagen hydrolysate, or placebo, taken once daily for 8 weeks. Skin elasticity, moisture, transepidermal water loss, and roughness were measured at baseline, 4 weeks, 8 weeks, and 4 weeks after stopping supplementation.","limitations":"Small sample size of only 69 participants (23 per group). Only women were included, so results may not generalize to men. Subgroup findings on moisture and water loss did not reach statistical significance. The study was 8 weeks long, which may not capture long-term effects or safety."},{"rthcId":"RPEP-02479","title":"Antagonist of GH-releasing hormone receptors alleviates experimental ocular inflammation.","authors":"Qin, Yong Jie; Chan, Sun On; Chong, Kelvin Kam Lung; Li, Benjamin Fuk Loi; Ng, Tsz Kin; Yip, Yolanda Wong Ying; Chen, Haoyu; Zhang, Mingzhi; Block, Norman L; Cheung, Herman S; Schally, Andrew V; Pang, Chi Pui","year":2014,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 111(51), 18303-8","doi":"10.1073/pnas.1421815112","pmid":"25489106","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02480","title":"Amylin and its analogs: a friend or foe for the treatment of Alzheimer's disease?","authors":"Qiu, Wei Qiao; Zhu, Haihao","year":2014,"journal":"Frontiers in aging neuroscience, 6, 186","doi":"10.3389/fnagi.2014.00186","pmid":"25120481","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02481","title":"Bioavailability of the anti-clostridial bacteriocin thuricin CD in gastrointestinal tract.","authors":"Rea, Mary C; Alemayehu, Debebe; Casey, Pat G; O'Connor, Paula M; Lawlor, Peadar G; Walsh, Maria; Shanahan, Fergus; Kiely, Barry; Ross, R Paul; Hill, Colin","year":2014,"journal":"Microbiology (Reading, England), 160(Pt 2), 439-445","doi":"10.1099/mic.0.068767-0","pmid":"24287693","tags":[],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Thuricin CD, a two-peptide bacteriocin produced by Bacillus thuringiensis, showed potent targeted killing of Clostridium difficile when delivered rectally in mice. One hour after rectal administration, C. difficile numbers dropped by more than 95% (over 1.5 log units) compared to controls (P<0.001), and by 6 hours there was a further 1.5 log reduction (P<0.05).\n\nHowever, oral delivery posed challenges. One of the two peptide components (Trn-β) was broken down by stomach enzymes pepsin and α-chymotrypsin, while the other (Trn-α) survived digestion and was detected in the intestines of pigs after oral feeding. Attempting to deliver the bacteriocin via spores of the producing bacterium also failed — nearly 99% of spores were excreted within 24 hours without producing detectable thuricin in the gut.","whyItMatters":"C. difficile infections cause severe diarrhea and colitis, particularly in hospitalized patients on antibiotics. Current treatments often use broad-spectrum antibiotics that damage beneficial gut bacteria and lead to high relapse rates. A narrow-spectrum peptide like thuricin CD that selectively kills C. difficile while sparing other gut bacteria could represent a fundamentally different treatment approach — if the delivery challenge can be solved.","specificNumbers":"n=40 mice (rectal study) · >95% C. difficile reduction at 1h · >1.5 log reduction (P<0.001) · further 1.5 log reduction at 6h (P<0.05) · 99% of spores excreted in 24h · n=30 mice (spore study)","methodology":"The researchers tested thuricin CD delivery through three approaches: (1) in vitro and in vivo enzyme digestion tests using porcine gastrointestinal models to assess peptide stability, (2) oral spore feeding in 30 mice to see if the producing bacterium could generate thuricin in the gut, and (3) rectal administration of thuricin CD in 40 mice infected with C. difficile ribotype 027, monitoring bacterial shedding at 1, 6, 12, and 24 hours post-treatment.","limitations":"This was an animal study in mice and pigs, so results may not translate directly to humans. The rectal delivery route, while effective, is less convenient than oral administration. The study did not assess long-term outcomes, relapse rates, or effects on the broader gut microbiome. Sample sizes were modest (10 mice per group in the rectal study)."},{"rthcId":"RPEP-02482","title":"Role of capsaicin-sensitive peripheral sensory neurons in anorexic responses to intravenous infusions of cholecystokinin, peptide YY-(3-36), and glucagon-like peptide-1 in rats.","authors":"Reidelberger, Roger; Haver, Alvin; Anders, Krista; Apenteng, Bettye","year":2014,"journal":"American journal of physiology. Endocrinology and metabolism, 307(8), E619-29","doi":"10.1152/ajpendo.00024.2014","pmid":"25117406","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02483","title":"Role of glucagon-like peptide-1 analogue versus amylin as an adjuvant therapy in type 1 diabetes in a closed loop setting with ePID algorithm.","authors":"Renukuntla, Venkat Sasidhar; Ramchandani, Neesha; Trast, Jeniece; Cantwell, Martin; Heptulla, Rubina A","year":2014,"journal":"Journal of diabetes science and technology, 8(5), 1011-7","doi":"10.1177/1932296814542153","pmid":"25030181","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02484","title":"The impact of dipeptidyl peptidase 4 inhibition on incretin effect, glucose tolerance, and gastrointestinal-mediated glucose disposal in healthy subjects.","authors":"Rhee, N A; Østoft, S H; Holst, J J; Deacon, C F; Vilsbøll, T; Knop, F K","year":2014,"journal":"European journal of endocrinology, 171(3), 353-62","doi":"10.1530/EJE-14-0314","pmid":"24935932","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02485","title":"Killing of melanoma cells and their metastases by human lactoferricin derivatives requires interaction with the cancer marker phosphatidylserine.","authors":"Riedl, Sabrina; Rinner, Beate; Schaider, Helmut; Lohner, Karl; Zweytick, Dagmar","year":2014,"journal":"Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine, 27(5), 981-97","doi":"10.1007/s10534-014-9749-0","pmid":"24838743","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02486","title":"Unexpectedly increased anorexigenic postprandial responses of PYY and GLP-1 to fast ice cream consumption in adult patients with Prader-Willi syndrome.","authors":"Rigamonti, A E; Bini, S; Grugni, G; Agosti, F; De Col, A; Mallone, M; Cella, S G; Sartorio, A","year":2014,"journal":"Clinical endocrinology, 81(4), 542-50","doi":"10.1111/cen.12395","pmid":"24372155","tags":[],"studyType":"clinical-trial","evidenceStrength":"preliminary","keyFinding":"In a surprising reversal of the normal pattern, fast eating (5 minutes) produced higher levels of the appetite-suppressing gut peptides GLP-1 and PYY in adults with Prader-Willi syndrome (PWS) compared to slow eating (30 minutes). In healthy normal-weight subjects, the expected opposite was true — slow eating produced greater peptide release and more satiety. In patients with simple obesity, neither eating rate significantly affected GLP-1 levels.\n\nFast eating also produced lower hunger and higher satiety ratings in PWS patients, mirroring the peptide findings. This reversed relationship suggests PWS involves a fundamentally different pathophysiological substrate governing gut-brain appetite signaling compared to simple obesity.","whyItMatters":"Prader-Willi syndrome is characterized by insatiable hunger (hyperphagia) and severe obesity. Understanding how gut appetite peptides respond differently in PWS versus simple obesity could reveal new therapeutic targets. The finding that fast eating paradoxically increases satiety peptides in PWS challenges conventional dietary advice to eat slowly, and suggests that the gut-brain axis dysfunction in PWS is qualitatively different from ordinary obesity — not just a more extreme version of it.","specificNumbers":"Fast feeding: 5 min · Slow feeding: 30 min · 3 groups: PWS, simple obesity, normal weight · GLP-1 and PYY measured postprandially · PWS: fast eating → higher GLP-1, PYY, satiety","methodology":"Three groups of adult participants — PWS patients, age-matched patients with simple obesity, and normal-weight subjects — consumed ice cream either quickly (5 minutes) or slowly (30 minutes). Blood levels of the anorexigenic (appetite-suppressing) gut peptides PYY and GLP-1 were measured after eating. Visual analog scales assessed subjective hunger and satiety feelings.","limitations":"Sample sizes were not reported in the abstract and are likely small given the rarity of PWS. The ice cream stimulus is a single food type and may not represent typical meals. The study measured postprandial peptide responses but did not assess actual food intake or long-term weight effects. The mechanisms underlying the reversed eating rate response in PWS remain unexplained."},{"rthcId":"RPEP-02487","title":"Incretin-based therapies, glucometabolic health and endovascular inflammation.","authors":"Rizzo, Manfredi; Nikolic, Dragana; Banach, Maciej; Patti, Angelo Maria; Montalto, Giuseppe; Rizvi, Ali A","year":2014,"journal":"Current pharmaceutical design, 20(31), 4953-60","doi":null,"pmid":"24320037","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02488","title":"Liraglutide decreases carotid intima-media thickness in patients with type 2 diabetes: 8-month prospective pilot study.","authors":"Rizzo, Manfredi; Chandalia, Manisha; Patti, Angelo Maria; Di Bartolo, Vittoria; Rizvi, Ali A; Montalto, Giuseppe; Abate, Nicola","year":2014,"journal":"Cardiovascular diabetology, 13, 49","doi":"10.1186/1475-2840-13-49","pmid":"24559258","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02489","title":"In vivo assessment of grafted cortical neural progenitor cells and host response to functionalized self-assembling peptide hydrogels and the implications for tissue repair.","authors":"Rodriguez, A L; Wang, T Y; Bruggeman, K F; Horgan, C C; Li, R; Williams, R J; Parish, C L; Nisbet, D R","year":2014,"journal":"Journal of materials chemistry. B, 2(44), 7771-7778","doi":"10.1039/c4tb01391c","pmid":"32261914","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Three Fmoc-SAP (fluorenylmethyloxycarbonyl self-assembling peptide) hydrogels containing bioactive sequences from laminin and fibronectin were tested in vivo in mouse brains. All three formulations demonstrated biocompatibility, with limited foreign body response and low cytotoxicity maintained for at least 28 days after transplantation.\n\nThe peptide hydrogels effectively supported the survival of grafted cortical neural progenitor cells and showed favorable interactions with the surrounding host brain tissue, attenuating the inflammatory response at the graft-host interface.","whyItMatters":"Cell transplantation therapies for brain injuries and neurological diseases are limited by poor cell survival and harmful immune reactions at the implant site. Self-assembling peptide hydrogels offer a promising solution because they can be easily engineered, mimic the body's natural tissue structure, and can be functionalized with biological signals. This study provides crucial in vivo evidence that these materials are safe and effective delivery vehicles for neural cells.","specificNumbers":"","methodology":"Researchers designed three self-assembling peptide hydrogels incorporating different bioactive sequences derived from extracellular matrix proteins (laminin and fibronectin). These hydrogels were loaded with cortical neural progenitor cells and transplanted into mouse brains. The team then monitored the foreign body response, cytotoxicity, cell survival, and graft-host tissue interactions over a 28-day period.","limitations":"The study was conducted in mice, and results may not directly translate to human brains, which have different immune responses and scale. The 28-day observation window, while informative, does not capture long-term outcomes. Specific quantitative data on cell survival rates and inflammatory markers were not detailed in the abstract. The study also did not assess whether the transplanted cells integrated functionally into neural circuits."},{"rthcId":"RPEP-02490","title":"The proinflammatory peptide substance P promotes blood-brain barrier breaching by breast cancer cells through changes in microvascular endothelial cell tight junctions.","authors":"Rodriguez, Pedro L; Jiang, Shuxian; Fu, Yigong; Avraham, Shalom; Avraham, Hava Karsenty","year":2014,"journal":"International journal of cancer, 134(5), 1034-44","doi":"10.1002/ijc.28433","pmid":"23934616","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02491","title":"High fat diet and GLP-1 drugs induce pancreatic injury in mice.","authors":"Rouse, Rodney; Xu, Lin; Stewart, Sharron; Zhang, Jun","year":2014,"journal":"Toxicology and applied pharmacology, 276(2), 104-14","doi":"10.1016/j.taap.2014.01.021","pmid":"24534256","tags":["glp-1","safety"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Both GLP-1 drugs tested — exenatide (a GLP-1 receptor agonist) and sitagliptin (a DPP-4 inhibitor) — caused significant pancreatic injury in mice compared to controls. The damage included acinar cell injury (hypertrophy, autophagy, apoptosis, necrosis, and atrophy), vascular injury, interstitial edema and inflammation, fat necrosis, and duct changes.\n\nImportantly, a high-fat diet made everything worse. Mice fed a high-fat diet already showed increased pancreatic changes compared to standard-diet mice, and when GLP-1 drugs were added on top of a high-fat diet, the pancreatic injury was exacerbated. Pro-inflammatory cytokines (TNFα, IL-1β, and KC) were significantly elevated in high-fat diet mice regardless of drug treatment.","whyItMatters":"This study directly addresses one of the most debated safety questions about GLP-1 drugs: do they increase pancreatitis risk? The finding that both exenatide and sitagliptin caused pancreatic injury in mice — and that a high-fat diet amplified the damage — is particularly relevant because the patients who take these drugs (people with type 2 diabetes) are often on high-fat diets. While mouse findings don't automatically translate to humans, this study provided early mechanistic evidence that fueled ongoing safety monitoring of GLP-1 drug classes.","specificNumbers":"","methodology":"Researchers fed mice either a high-fat diet or standard diet for 6 weeks to create insulin resistance, then administered exenatide or sitagliptin daily for an additional 6 weeks. They measured body weight, blood glucose, pro-inflammatory cytokines (TNFα, IL-1β, KC), and performed semi-quantitative grading of pancreatic tissue changes including acinar cell injury, vascular injury, inflammation, and duct changes.","limitations":"This is a mouse study, and pancreatic physiology differs between mice and humans. The drug doses and duration may not directly correspond to human therapeutic regimens. The study used semi-quantitative grading rather than fully quantitative measurements. No long-term follow-up was performed to assess whether pancreatic changes were reversible after stopping treatment."},{"rthcId":"RPEP-02492","title":"The glucagon-like peptide-1-based therapeutics exenatide and saxagliptin did not cause detrimental effects on the pancreas in mice, rats, dogs and monkeys.","authors":"Roy, D; Chadwick, K D; Tatarkiewicz, K; LaCerte, C; Bergholm, A-M; Brodie, T; Mangipudy, R S; Parkes, D; Graziano, M J; Reilly, T P","year":2014,"journal":"Diabetes, obesity & metabolism, 16(10), 910-21","doi":"10.1111/dom.12294","pmid":"24666399","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In the most comprehensive preclinical pancreatic safety assessment ever conducted for GLP-1-based drugs:\n\n- More than 70 GLP-regulated toxicology studies were conducted across mice, rats, dogs, and monkeys\n- Over 2,400 pancreata examined from exenatide-treated animals\n- Over 1,700 pancreata examined from saxagliptin-treated animals\n- Treatment lasted up to 2 years in rodents and 12 months in non-rodents\n- Doses reached 130× human exposure for exenatide and 2,200× for saxagliptin\n- Neither drug caused microscopic changes indicating acute or chronic pancreatic injury\n- No evidence of pancreatitis, pre-neoplastic changes, or pancreatic cancer in any species\n\nThese data substantially support the pancreatic safety of GLP-1-based therapies.","whyItMatters":"This study provides the most definitive preclinical evidence addressing one of the biggest safety concerns ever raised about GLP-1 drugs — the fear that they cause pancreatitis or pancreatic cancer. With over 4,100 pancreata examined at extreme drug exposures, the complete absence of adverse findings provides powerful reassurance. This data was instrumental in regulatory agencies concluding that GLP-1 drugs do not pose a significant pancreatic risk.","specificNumbers":"","methodology":"This was a comprehensive integration of regulatory toxicology data from more than 70 non-clinical studies conducted under Good Laboratory Practice (GLP) regulations in accordance with ICH and FDA guidelines. Studies included mice, rats, dogs, and non-human primates. Comprehensive pancreas assessments evaluated endocrine and exocrine tissue for any drug-related microscopic changes at multiple time points and dose levels.","limitations":"This is an industry-sponsored study from the manufacturer of exenatide and saxagliptin, which could introduce bias. Animal toxicology, even across multiple species, cannot perfectly predict human responses. The studies assessed histological endpoints — subclinical functional changes may not have been captured. Chronic low-grade inflammation without visible microscopic changes is theoretically possible. The 2-year maximum duration in rodents may not capture very long-term effects relevant to lifelong human use."},{"rthcId":"RPEP-02493","title":"Research resource: Gene profiling of G protein-coupled receptors in the arcuate nucleus of the female.","authors":"Rønnekleiv, Oline K; Fang, Yuan; Zhang, Chunguang; Nestor, Casey C; Mao, Peizhong; Kelly, Martin J","year":2014,"journal":"Molecular endocrinology (Baltimore, Md.), 28(8), 1362-80","doi":"10.1210/me.2014-1103","pmid":"24933249","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02494","title":"Cerebrospinal fluid neuropeptide Y in combat veterans with and without posttraumatic stress disorder.","authors":"Sah, Renu; Ekhator, Nosakhare N; Jefferson-Wilson, Lena; Horn, Paul S; Geracioti, Thomas D","year":2014,"journal":"Psychoneuroendocrinology, 40, 277-83","doi":"10.1016/j.psyneuen.2013.10.017","pmid":"24485499","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02495","title":"How does growth hormone releasing hexapeptide self-assemble in nanotubes?","authors":"Santana, Héctor; Avila, Cesar L; Cabrera, Ingrid; Páez, Rolando; Falcón, Viviana; Pessoa, Adalberto; Ventosa, Nora; Veciana, Jaume; Itri, Rosangela; Barbosa, Leandro Ramos Souza","year":2014,"journal":"Soft matter, 10(46), 9260-9","doi":"10.1039/c4sm01693a","pmid":"25325399","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GHRP-6 (His-(D-Trp)-Ala-Trp-(D-Phe)-Lys-NH2) spontaneously forms long nanotubes in aqueous solution at pH 7.0 and 22°C. The nanotubes have inner and outer cross-sections of 6.7 nm and 13.4 nm respectively. Molecular dynamics simulations revealed the peptides self-assemble in a partially interdigitated structure: positively charged amino termini at the peptide-water interface, neutral carboxy termini buried in the hydrophobic core, and Lys-6 stretching its positive charge to the cylinder surface. At higher concentrations, nanotubes pack in a hexagonal arrangement with ~15 nm center-to-center spacing. The nanostructures are stable in solution and when transferred to solid supports.","whyItMatters":"Peptide self-assembly into well-defined nanostructures is a rapidly growing field in nanotechnology and drug delivery. GHRP-6's ability to form stable nanotubes spontaneously — without external triggers — makes it an interesting building block for nanomaterials. Understanding how short peptides form organized structures could enable design of peptide-based drug delivery systems and biomaterials.","specificNumbers":"","methodology":"The self-assembly was characterized using small-angle X-ray scattering (SAXS), transmission electron microscopy (TEM), and molecular dynamics (MD) simulations. SAXS provided structural dimensions and packing patterns, TEM visualized the nanotube morphology, and MD simulations revealed the molecular arrangement and driving forces behind self-assembly.","limitations":"This is a biophysics/materials characterization study with no biological or therapeutic testing. The self-assembly was observed under specific laboratory conditions (pH 7.0, 22°C) that may not represent physiological environments. Whether the nanotube formation affects GHRP-6's biological activity or could be harnessed for drug delivery was not explored."},{"rthcId":"RPEP-02496","title":"Inflammation in CRPS: role of the sympathetic supply.","authors":"Schlereth, Tanja; Drummond, Peter D; Birklein, Frank","year":2014,"journal":"Autonomic neuroscience : basic & clinical, 182, 102-7","doi":"10.1016/j.autneu.2013.12.011","pmid":"24411269","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02497","title":"BPC 157 and blood vessels.","authors":"Seiwerth, Sven; Brcic, Luka; Vuletic, Lovorka Batelja; Kolenc, Danijela; Aralica, Gorana; Misic, Marija; Zenko, Anita; Drmic, Domagoj; Rucman, Rudolf; Sikiric, Predrag","year":2014,"journal":"Current pharmaceutical design, 20(7), 1121-5","doi":null,"pmid":"23782145","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02498","title":"Thymosin α1 activates complement receptor-mediated phagocytosis in human monocyte-derived macrophages.","authors":"Serafino, Annalucia; Pica, Francesca; Andreola, Federica; Gaziano, Roberta; Moroni, Noemi; Moroni, Gabriella; Zonfrillo, Manuela; Pierimarchi, Pasquale; Sinibaldi-Vallebona, Paola; Garaci, Enrico","year":2014,"journal":"Journal of innate immunity, 6(1), 72-88","doi":"10.1159/000351587","pmid":"23797159","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Thymosin alpha-1 exposure caused human monocyte-derived macrophages to assume an activated shape and dramatically increased their ability to engulf fluorescent beads, zymosan particles, and Aspergillus niger conidia (fungal spores). The phagocytosis and killing of fungal spores began as soon as 30 minutes after exposure.\n\nThe effect was dose-dependent and notably occurred with low levels of pro-inflammatory cytokines (TNF-α and IL-6) and unchanged Toll-like receptor expression — meaning Tα1 boosted pathogen killing without triggering excessive inflammation. The mechanism depended on intact microtubules and protein kinase C activity, and operated through complement receptor-mediated phagocytosis with a distinctive pattern of vinculin and actin recruitment at the phagosome.","whyItMatters":"Thymosin alpha-1 is already used in clinical trials worldwide for infections and cancer, but understanding exactly how it works is crucial for optimizing its use. This study reveals that Tα1 acts as a rapid and potent activator of innate immunity that boosts pathogen killing while keeping inflammation in check — a desirable combination that could be particularly valuable for immunocompromised patients vulnerable to fungal infections like aspergillosis.","specificNumbers":"","methodology":"Researchers isolated human monocytes and differentiated them into macrophages in culture. These macrophages were exposed to thymosin alpha-1 at various doses and time points, then challenged with fluorescent beads, zymosan particles, or Aspergillus niger spores. Phagocytosis was measured by internalization assays, and killing was assessed directly. Cytokine production, Toll-like receptor expression, cytoskeletal involvement, and protein kinase C activity were all analyzed to determine the mechanism.","limitations":"This is an in vitro study using cultured human macrophages, which may not fully replicate the complex immune environment in living patients. The study used a single fungal species (Aspergillus niger) and it is unclear if the results would generalize to other pathogens. Specific sample sizes for the cell culture experiments are not detailed in the abstract. Clinical efficacy cannot be inferred from these laboratory findings alone."},{"rthcId":"RPEP-02499","title":"Intranasal neuropeptide Y reverses anxiety and depressive-like behavior impaired by single prolonged stress PTSD model.","authors":"Serova, L I; Laukova, M; Alaluf, L G; Pucillo, L; Sabban, E L","year":2014,"journal":"European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 24(1), 142-7","doi":"10.1016/j.euroneuro.2013.11.007","pmid":"24326087","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02500","title":"Dose-dependent changes in the levels of free and peptide forms of hydroxyproline in human plasma after collagen hydrolysate ingestion.","authors":"Shigemura, Yasutaka; Kubomura, Daiki; Sato, Yoshio; Sato, Kenji","year":2014,"journal":"Food chemistry, 159, 328-32","doi":"10.1016/j.foodchem.2014.02.091","pmid":"24767063","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02501","title":"Stable gastric pentadecapeptide BPC 157-NO-system relation.","authors":"Sikiric, Predrag; Seiwerth, Sven; Rucman, Rudolf; Turkovic, Branko; Rokotov, Dinko Stancic; Brcic, Luka; Sever, Marko; Klicek, Robert; Radic, Bozo; Drmic, Domagoj; Ilic, Spomenko; Kolenc, Danijela; Aralica, Gorana; Stupnisek, Mirjana; Suran, Jelena; Barisic, Ivan; Dzidic, Senka; Vrcic, Hrvoje; Sebecic, Bozidar","year":2014,"journal":"Current pharmaceutical design, 20(7), 1126-35","doi":null,"pmid":"23755725","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02502","title":"Killing of Mycobacterium avium by lactoferricin peptides: improved activity of arginine- and D-amino-acid-containing molecules.","authors":"Silva, Tânia; Magalhães, Bárbara; Maia, Sílvia; Gomes, Paula; Nazmi, Kamran; Bolscher, Jan G M; Rodrigues, Pedro N; Bastos, Margarida; Gomes, Maria Salomé","year":2014,"journal":"Antimicrobial agents and chemotherapy, 58(6), 3461-7","doi":"10.1128/AAC.02728-13","pmid":"24709266","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02503","title":"Synthesis, biophysical, and pharmacological evaluation of the melanocortin agonist AST3-88: modifications of peptide backbone at Trp 7 position lead to a potent, selective, and stable ligand of the melanocortin 4 receptor (MC4R).","authors":"Singh, Anamika; Dirain, Marvin L; Wilczynski, Andrzej; Chen, Chi; Gosnell, Blake A; Levine, Allen S; Edison, Arthur S; Haskell-Luevano, Carrie","year":2014,"journal":"ACS chemical neuroscience, 5(10), 1020-31","doi":"10.1021/cn5000953","pmid":"25141170","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02504","title":"Multicentre prospective validation of a urinary peptidome-based classifier for the diagnosis of type 2 diabetic nephropathy.","authors":"Siwy, Justyna; Schanstra, Joost P; Argiles, Angel; Bakker, Stephan J L; Beige, Joachim; Boucek, Petr; Brand, Korbinian; Delles, Christian; Duranton, Flore; Fernandez-Fernandez, Beatriz; Jankowski, Marie-Luise; Al Khatib, Mohammad; Kunt, Thomas; Lajer, Maria; Lichtinghagen, Ralf; Lindhardt, Morten; Maahs, David M; Mischak, Harald; Mullen, William; Navis, Gerjan; Noutsou, Marina; Ortiz, Alberto; Persson, Frederik; Petrie, John R; Roob, Johannes M; Rossing, Peter; Ruggenenti, Piero; Rychlik, Ivan; Serra, Andreas L; Snell-Bergeon, Janet; Spasovski, Goce; Stojceva-Taneva, Olivera; Trillini, Matias; von der Leyen, Heiko; Winklhofer-Roob, Brigitte M; Zürbig, Petra; Jankowski, Joachim","year":2014,"journal":"Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 29(8), 1563-70","doi":"10.1093/ndt/gfu039","pmid":"24589724","tags":["peptide-biomarkers","kidney-disease"],"studyType":"prospective-validation","evidenceStrength":"moderate","keyFinding":"A urinary peptide-based diagnostic test called CKD273 — which measures 273 peptide fragments in urine — was validated across 9 different medical centers with remarkable consistency. The test achieved areas under the curve (AUC) of 0.95 to 1.00 for detecting diabetic nephropathy progression in type 2 diabetes patients, meaning it was nearly perfect at distinguishing those whose kidney disease would progress.\n\nThe classifier worked reliably regardless of patient age (16-89 years), gender, or what type of container was used to collect the urine. The most consistently detected peptides came from blood-derived and extracellular matrix proteins, suggesting these are the most robust biomarkers for kidney damage in diabetes.","whyItMatters":"Diabetic kidney disease (nephropathy) is one of the most devastating complications of type 2 diabetes and the leading cause of kidney failure worldwide. Current detection methods often catch the disease too late for effective intervention. A urine test that can predict kidney disease progression before significant damage occurs could allow earlier treatment and potentially prevent kidney failure. The fact that CKD273 works consistently across multiple centers and is unaffected by age, gender, or sample handling makes it practical for real-world clinical use.","specificNumbers":"n=165 · 9 centers · 273 urinary peptides measured · AUC 0.95-1.00 · Age range tested: 16-89 years · Independent of gender and sample container type","methodology":"Prospective multicentre validation study within the PRIORITY trial. 165 type 2 diabetes patients provided urine samples across 9 different institutions. Samples were analyzed using the CKD273 urinary proteomics classifier, which measures 273 specific peptide fragments using capillary electrophoresis coupled with mass spectrometry. Researchers tested consistency across centers and evaluated whether age, gender, or sample storage containers affected results.","limitations":"Sample size of 165 is moderate for a validation study. This is a validation of the classifier's analytical consistency, not a long-term outcomes study proving it prevents kidney failure. The study was conducted within a specific trial population (PRIORITY trial participants), which may not fully represent all type 2 diabetes patients. Cost and accessibility of proteomics-based testing may limit widespread adoption."},{"rthcId":"RPEP-02505","title":"The kisspeptin-GnRH pathway in human reproductive health and disease.","authors":"Skorupskaite, Karolina; George, Jyothis T; Anderson, Richard A","year":2014,"journal":"Human reproduction update, 20(4), 485-500","doi":"10.1093/humupd/dmu009","pmid":"24615662","tags":[],"studyType":"review","evidenceStrength":"strong","keyFinding":"Kisspeptin is the principal upstream regulator of GnRH secretion, critical for puberty onset, sex steroid feedback, and adult fertility in both sexes. It works through the KNDy (kisspeptin-neurokinin B-dynorphin) pathway, where neurokinin B provides stimulatory and dynorphin provides inhibitory paracrine input to control pulsatile GnRH release.\n\nWhen administered to humans in various forms, routes, and doses, kisspeptin robustly stimulates LH secretion and pulse frequency. This creates two therapeutic directions: boosting LH in conditions with low pulsatility (hypothalamic amenorrhea, hypogonadotropic hypogonadism) and reducing it in conditions with excess LH (like PCOS).","whyItMatters":"Understanding kisspeptin's role as the master switch for reproductive hormone signaling has transformed reproductive endocrinology. It provides a more upstream and potentially more precise target than directly manipulating GnRH — opening doors for gentler IVF protocols, new treatments for infertility disorders, and novel approaches to conditions like PCOS where hormone pulsatility is disrupted.","specificNumbers":"KNDy pathway: kisspeptin + neurokinin B + dynorphin · Kisspeptin stimulates LH secretion and LH pulse frequency in humans · Therapeutic targets: hypothalamic amenorrhea, hypogonadotropic hypogonadism, PCOS","methodology":"Systematic literature review of all English-language PubMed articles through January 2014 on kisspeptin-GnRH pathway in human reproductive health, supplemented by reference list screening. Focused on human studies with supporting animal data.","limitations":"As a review, this synthesizes existing evidence rather than generating new data. Most kisspeptin administration studies in humans at the time were small and short-term. Long-term safety and efficacy of kisspeptin-based therapies had not been established. Some findings relied heavily on animal models that may not fully translate to humans."},{"rthcId":"RPEP-02506","title":"Peptides and food intake.","authors":"Sobrino Crespo, Carmen; Perianes Cachero, Aránzazu; Puebla Jiménez, Lilian; Barrios, Vicente; Arilla Ferreiro, Eduardo","year":2014,"journal":"Frontiers in endocrinology, 5, 58","doi":"10.3389/fendo.2014.00058","pmid":"24795698","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02507","title":"Engineered 3D bioimplants using elastomeric scaffold, self-assembling peptide hydrogel, and adipose tissue-derived progenitor cells for cardiac regeneration.","authors":"Soler-Botija, Carolina; Bagó, Juli R; Llucià-Valldeperas, Aida; Vallés-Lluch, Ana; Castells-Sala, Cristina; Martínez-Ramos, Cristina; Fernández-Muiños, Teresa; Chachques, Juan Carlos; Pradas, Manuel Monleón; Semino, Carlos E; Bayes-Genis, Antoni","year":2014,"journal":"American journal of translational research, 6(3), 291-301","doi":null,"pmid":"24936221","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The bioimplant consisting of polycaprolactone scaffold filled with PuraMatrix peptide hydrogel and seeded with adipose tissue-derived progenitor cells successfully integrated with injured myocardium in mice. Bioluminescence tracking showed de novo and progressive increases in cardiac-specific promoter expression, indicating stem cell differentiation toward cardiac lineages. Functional blood vessels traversed the myocardium-implant interface. Echocardiography revealed a detectable positive effect on cardiac function compared to controls.","whyItMatters":"Heart attack damage is currently irreversible — scar tissue replaces functional muscle. While stem cell therapy has shown promise, delivering cells to the heart and keeping them alive in the hostile post-infarction environment has been a major challenge. The peptide hydrogel in this bioimplant provides a biocompatible three-dimensional environment that supports cell survival, promotes vascularization, and facilitates cardiac differentiation — addressing key barriers in cardiac regenerative medicine.","specificNumbers":"","methodology":"Subcutaneous adipose tissue-derived progenitor cells were doubly transduced with lentiviral vectors carrying bioluminescent-fluorescent reporters under cardiac-specific promoters. Cells were seeded into engineered bioimplants (polycaprolactone methacryloyloxyethyl ester scaffold filled with PuraMatrix peptide hydrogel) and transplanted onto injured myocardium in a mouse model of myocardial infarction. Cell fate was tracked via bioluminescence and fluorescence. Cardiac function was assessed by echocardiography, and vascularization was evaluated histologically.","limitations":"This is a small animal (mouse) study, and translation to human-sized hearts involves significant scaling challenges. The specific number of animals and magnitude of functional improvement were not detailed in the abstract. Long-term durability of the implant and sustained cardiac benefit were not assessed. The open-label design without detailed quantification of functional improvement limits conclusions about efficacy magnitude."},{"rthcId":"RPEP-02508","title":"The role of ghrelin in weight-regulation disorders: implications in clinical practice.","authors":"Solomou, Solomis; Korbonits, Márta","year":2014,"journal":"Hormones (Athens, Greece), 13(4), 458-75","doi":"10.14310/horm.2002.1551","pmid":"25555181","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02509","title":"Taste matters - effects of bypassing oral stimulation on hormone and appetite responses.","authors":"Spetter, Maartje S; Mars, Monica; Viergever, Max A; de Graaf, Cees; Smeets, Paul A M","year":2014,"journal":"Physiology & behavior, 137, 9-17","doi":"10.1016/j.physbeh.2014.06.021","pmid":"25008799","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02510","title":"Structural-functional analysis of the third transmembrane domain of the corticotropin-releasing factor type 1 receptor: role in activation and allosteric antagonism.","authors":"Spyridaki, Katerina; Matsoukas, Minos-Timotheos; Cordomi, Arnau; Gkountelias, Kostas; Papadokostaki, Maria; Mavromoustakos, Thomas; Logothetis, Diomedes E; Margioris, Andrew N; Pardo, Leonardo; Liapakis, George","year":2014,"journal":"The Journal of biological chemistry, 289(27), 18966-77","doi":"10.1074/jbc.M113.544460","pmid":"24838244","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02511","title":"Tachykinins and their receptors: contributions to physiological control and the mechanisms of disease.","authors":"Steinhoff, Martin S; von Mentzer, Bengt; Geppetti, Pierangelo; Pothoulakis, Charalabos; Bunnett, Nigel W","year":2014,"journal":"Physiological reviews, 94(1), 265-301","doi":"10.1152/physrev.00031.2013","pmid":"24382888","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02512","title":"Skin electroporation of a plasmid encoding hCAP-18/LL-37 host defense peptide promotes wound healing.","authors":"Steinstraesser, Lars; Lam, Martin C; Jacobsen, Frank; Porporato, Paolo E; Chereddy, Kiran Kumar; Becerikli, Mustafa; Stricker, Ingo; Hancock, Robert Ew; Lehnhardt, Marcus; Sonveaux, Pierre; Préat, Véronique; Vandermeulen, Gaëlle","year":2014,"journal":"Molecular therapy : the journal of the American Society of Gene Therapy, 22(4), 734-42","doi":"10.1038/mt.2013.258","pmid":"24394186","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02513","title":"Incretin-mimetic therapies and pancreatic disease: a review of observational data.","authors":"Suarez, Elizabeth A; Koro, Carol E; Christian, Jennifer B; Spector, Alicia D; Araujo, Andre B; Abraham, Sybil","year":2014,"journal":"Current medical research and opinion, 30(12), 2471-81","doi":"10.1185/03007995.2014.960515","pmid":"25180611","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02514","title":"Novel GHRH antagonists suppress the growth of human malignant melanoma by restoring nuclear p27 function.","authors":"Szalontay, Luca; Schally, Andrew V; Popovics, Petra; Vidaurre, Irving; Krishan, Awtar; Zarandi, Marta; Cai, Ren-Zhi; Klukovits, Anna; Block, Norman L; Rick, Ferenc G","year":2014,"journal":"Cell cycle (Georgetown, Tex.), 13(17), 2790-7","doi":"10.4161/15384101.2015.945879","pmid":"25486366","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02515","title":"Highly accurate quantification of hydroxyproline-containing peptides in blood using a protease digest of stable isotope-labeled collagen.","authors":"Taga, Yuki; Kusubata, Masashi; Ogawa-Goto, Kiyoko; Hattori, Shunji","year":2014,"journal":"Journal of agricultural and food chemistry, 62(50), 12096-102","doi":"10.1021/jf5039597","pmid":"25417748","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02516","title":"Proteome-wide identification of SUMO2 modification sites.","authors":"Tammsalu, Triin; Matic, Ivan; Jaffray, Ellis G; Ibrahim, Adel F M; Tatham, Michael H; Hay, Ronald T","year":2014,"journal":"Science signaling, 7(323), rs2","doi":"10.1126/scisignal.2005146","pmid":"24782567","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02517","title":"Effects of nebivolol on biomarkers in elderly patients with heart failure.","authors":"Taneja, Anil K; Gaze, David; Coats, Andrew J S; Dumitrascu, Dan; Spinarova, Lenka; Collinson, Paul; Roughton, Michael; Flather, Marcus D","year":2014,"journal":"International journal of cardiology, 175(2), 253-60","doi":"10.1016/j.ijcard.2014.05.018","pmid":"24877590","tags":[],"studyType":"randomized controlled trial","evidenceStrength":"moderate","keyFinding":"In this substudy of the SENIORS trial examining 106 elderly heart failure patients, nebivolol did not produce statistically significant changes in natriuretic peptides (NT-proBNP, pro-ANP), cytokines (TNF-α, sFas, sFas-L), or nitric oxide markers (ADMA, SDMA, arginine, citrulline) compared to placebo over 12 months.\n\nHowever, left ventricular ejection fraction improved significantly in the nebivolol group (from 35% to 43%) compared to placebo (35% to 34%, P=0.01). NT-proBNP showed a non-significant trend toward increase in the nebivolol group (P=0.08), while soluble Fas trended upward in the placebo group (P=0.08).","whyItMatters":"Natriuretic peptides like NT-proBNP are the most widely used biomarkers for monitoring heart failure severity. This study reveals a surprising disconnect: nebivolol improved heart function (ejection fraction) without lowering natriuretic peptide levels. This challenges the assumption that effective heart failure treatment should always reduce circulating peptide biomarkers and suggests that the relationship between cardiac improvement and peptide levels is more complex than previously thought.","specificNumbers":"n=106 enrolled · n=75 with follow-up · LVEF 35%→43% nebivolol vs 35%→34% placebo (P=0.01) · NT-proBNP trend P=0.08 · sFas trend P=0.08 · 12-month follow-up","methodology":"Prespecified substudy of the SENIORS randomized controlled trial. 106 elderly heart failure patients were enrolled, with 75 completing baseline and at least one follow-up sample. Researchers measured 12 biomarkers at baseline, 6 months, and 12 months, comparing nebivolol to placebo in a double-blind design.","limitations":"Small substudy sample (75 analyzable patients) limited statistical power to detect biomarker changes. The study may have been underpowered for the number of biomarkers tested. Results represent a subset of the larger SENIORS trial and may not reflect the full trial population."},{"rthcId":"RPEP-02518","title":"Inflammation enhances Y1 receptor signaling, neuropeptide Y-mediated inhibition of hyperalgesia, and substance P release from primary afferent neurons.","authors":"Taylor, B K; Fu, W; Kuphal, K E; Stiller, C-O; Winter, M K; Chen, W; Corder, G F; Urban, J H; McCarson, K E; Marvizon, J C","year":2014,"journal":"Neuroscience, 256, 178-94","doi":"10.1016/j.neuroscience.2013.10.054","pmid":"24184981","tags":["neuropeptide-y","pain","inflammation"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Neuropeptide Y (NPY) acting through Y1 receptors in the spinal cord inhibits the release of substance P, a key pain-signaling molecule. This anti-pain effect was significantly enhanced during inflammation — Y1 receptor signaling increased after inflammatory injury, with higher receptor-G protein coupling affinity in inflamed animals compared to uninjured controls.\n\nSpecifically, NPY decreased capsaicin-evoked substance P release in spinal cord microdialysate and reduced NK1 receptor internalization (a marker of substance P release) triggered by non-painful stimulation after carrageenan-induced inflammation. After complete Freund's adjuvant (CFA) inflammation, a Y1-selective agonist reduced pain-evoked NK1R internalization in inflamed rats but not in uninjured controls, indicating that inflammation itself enhances the pain-inhibitory capacity of the NPY-Y1 system.","whyItMatters":"Chronic pain conditions involving inflammation are notoriously difficult to treat. This study reveals that the body's own neuropeptide Y system becomes more effective at suppressing pain signals during inflammation — essentially, the brain's natural pain-relief system ramps up when it's needed most. Understanding this mechanism could lead to new pain treatments that enhance NPY-Y1 receptor signaling rather than relying on opioids.","specificNumbers":"","methodology":"Researchers used multiple techniques in rats and mice: spinal cord microdialysis to measure substance P release, NK1 receptor internalization as a marker of substance P signaling, behavioral pain tests (mechanical hyperalgesia, mechanical and cold allodynia), immunohistochemistry to map Y1 receptor locations in dorsal root ganglia and spinal cord neurons, spinal cord slice preparations with attached dorsal roots, and GTPγS binding assays to measure Y1 receptor-G protein coupling. Inflammation was induced using either carrageenan or complete Freund's adjuvant (CFA) injections into the paw.","limitations":"This was an animal study conducted in rats and mice, so the results may not directly translate to human pain conditions. The study used experimentally induced inflammation models (carrageenan and CFA) which may differ from naturally occurring chronic inflammatory pain. Additionally, the complex neural circuitry of the dorsal horn made it difficult to determine precise co-localization of Y1 receptors with pain neuropeptides at nerve terminals."},{"rthcId":"RPEP-02519","title":"Treatment with steroid hormones and morphine alters general activity, sexual behavior, and opioid gene expression in female rats.","authors":"Teodorov, E; Camarini, R; Bernardi, M M; Felicio, L F","year":2014,"journal":"Life sciences, 104(1-2), 47-54","doi":"10.1016/j.lfs.2014.03.021","pmid":"24699004","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02520","title":"Detecting peptidic drugs, drug candidates and analogs in sports doping: current status and future directions.","authors":"Thevis, Mario; Thomas, Andreas; Schänzer, Wilhelm","year":2014,"journal":"Expert review of proteomics, 11(6), 663-73","doi":"10.1586/14789450.2014.965159","pmid":"25382550","tags":[],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Anti-doping laboratories have developed multiple analytical methods to detect a wide range of peptide drugs in athlete samples. These include chromatographic-mass spectrometric, electrophoretic, immunological, and combined approaches capable of identifying peptides across all molecular sizes.\n\nLow-molecular-weight peptides detected include growth hormone-releasing peptides (GHRPs), ARA-290, TB-500, AOD-9604, CJC-1295, desmopressin, LH-releasing hormones, and synacthen. Intermediate-sized peptides include insulins, IGF-1 and analogs, mechano growth factor, growth hormone, hCG, and erythropoietin. Larger peptides like stamulumab can also be detected.\n\nHowever, a significant gap remained between what was technically possible in research settings and what could be reliably implemented in routine daily testing of athlete samples.","whyItMatters":"Peptide doping represents one of the most challenging detection problems in sports drug testing. Unlike traditional small-molecule drugs, peptides are present at extremely low concentrations, are rapidly degraded in the body, and often closely resemble natural human proteins. This review catalogues the state of detection science as of 2014, revealing both the impressive range of peptides that anti-doping labs could identify and the practical limitations preventing comprehensive routine testing.","specificNumbers":"Blood, serum, and urine tested · Lower MW peptides: GHRPs, TB-500, AOD-9604, CJC-1295 · Mid MW: insulins, IGF-1, GH, EPO · Higher MW: stamulumab","methodology":"This is an expert review published in Expert Review of Proteomics that surveys the analytical methods used by anti-doping laboratories to detect peptidic drugs. It covers chromatographic-mass spectrometric techniques, electrophoretic methods, immunological assays, and combined approaches, categorizing detectable peptides by molecular weight.","limitations":"As a 2014 review, the detection landscape has evolved significantly with newer mass spectrometry techniques and expanded WADA prohibited lists. The review acknowledges a gap between research-grade detection capability and routine laboratory practice. It does not quantify false positive/negative rates for specific assays."},{"rthcId":"RPEP-02521","title":"A high-throughput LC-MS/MS screen for GHRP in equine and human urine, featuring peptide derivatization for improved chromatography.","authors":"Timms, Mark; Hall, Nikki; Levina, Vita; Vine, John; Steel, Rohan","year":2014,"journal":"Drug testing and analysis, 6(10), 985-95","doi":"10.1002/dta.1624","pmid":"24574167","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02522","title":"In vitro pharmacological evaluation of the radiolabeled C-terminal substance P analogue Lys-Phe-Phe-Gly-Leu-Met-NH2: Does a specific binding site exist?","authors":"Tomczyszyn, Aleksandra; Csibrany, Balazs; Keresztes, Attila; Mallareddy, Jayapal Reddy; Dyniewicz, Jolanta; Misicka, Aleksandra; Toth, Geza; Lipkowski, Andrzej W","year":2014,"journal":"Folia neuropathologica, 52(4), 383-9","doi":null,"pmid":"25574743","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02523","title":"Devil's Claw to suppress appetite--ghrelin receptor modulation potential of a Harpagophytum procumbens root extract.","authors":"Torres-Fuentes, Cristina; Theeuwes, Wessel F; McMullen, Michael K; McMullen, Anna K; Dinan, Timothy G; Cryan, John F; Schellekens, Harriët","year":2014,"journal":"PloS one, 9(7), e103118","doi":"10.1371/journal.pone.0103118","pmid":"25068823","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02524","title":"Diversity-oriented synthesis of azapeptides with basic amino acid residues: aza-lysine, aza-ornithine, and aza-arginine.","authors":"Traoré, Mariam; Doan, Ngoc-Duc; Lubell, William D","year":2014,"journal":"Organic letters, 16(13), 3588-91","doi":"10.1021/ol501586y","pmid":"24959890","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02525","title":"A CRPS-IgG-transfer-trauma model reproducing inflammatory and positive sensory signs associated with complex regional pain syndrome.","authors":"Tékus, Valéria; Hajna, Zsófia; Borbély, Éva; Markovics, Adrienn; Bagoly, Teréz; Szolcsányi, János; Thompson, Victoria; Kemény, Ágnes; Helyes, Zsuzsanna; Goebel, Andreas","year":2014,"journal":"Pain, 155(2), 299-308","doi":"10.1016/j.pain.2013.10.011","pmid":"24145209","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02526","title":"Peptides stimulate expression of signal molecules in neuronal cultures from animals of different age.","authors":"Umnov, R S; Lin'kova, N S; Khavinson, V Kh","year":2014,"journal":"Bulletin of experimental biology and medicine, 157(5), 701-4","doi":"10.1007/s10517-014-2646-2","pmid":"25257443","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02527","title":"Mapping substance P binding sites on the neurokinin-1 receptor using genetic incorporation of a photoreactive amino acid.","authors":"Valentin-Hansen, Louise; Park, Minyoung; Huber, Thomas; Grunbeck, Amy; Naganathan, Saranga; Schwartz, Thue W; Sakmar, Thomas P","year":2014,"journal":"The Journal of biological chemistry, 289(26), 18045-54","doi":"10.1074/jbc.M113.527085","pmid":"24831006","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02528","title":"Effects of glucagon-like peptide 1 on appetite and body weight: focus on the CNS.","authors":"van Bloemendaal, L; Ten Kulve, J S; la Fleur, S E; Ijzerman, R G; Diamant, M","year":2014,"journal":"The Journal of endocrinology, 221(1), T1-16","doi":"10.1530/JOE-13-0414","pmid":"24323912","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02529","title":"GLP-1 receptor activation modulates appetite- and reward-related brain areas in humans.","authors":"van Bloemendaal, Liselotte; IJzerman, Richard G; Ten Kulve, Jennifer S; Barkhof, Frederik; Konrad, Robert J; Drent, Madeleine L; Veltman, Dick J; Diamant, Michaela","year":2014,"journal":"Diabetes, 63(12), 4186-96","doi":"10.2337/db14-0849","pmid":"25071023","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02530","title":"Effects of the once-daily GLP-1 analog liraglutide on gastric emptying, glycemic parameters, appetite and energy metabolism in obese, non-diabetic adults.","authors":"van Can, J; Sloth, B; Jensen, C B; Flint, A; Blaak, E E; Saris, W H M","year":2014,"journal":"International journal of obesity (2005), 38(6), 784-93","doi":"10.1038/ijo.2013.162","pmid":"23999198","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02531","title":"Estrogen-like potentiation of ghrelin-stimulated GH secretion by fulvestrant, a putatively selective ER antagonist, in postmenopausal women.","authors":"Veldhuis, Johannes D; Yang, Rebecca J; Wigham, Jean R; Erickson, Dana; Miles, John C; Bowers, Cyril Y","year":2014,"journal":"The Journal of clinical endocrinology and metabolism, 99(12), E2557-64","doi":"10.1210/jc.2014-2633","pmid":"25210881","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Fulvestrant (FUL) vs placebo in postmenopausal women produced paradoxical mixed effects:\n\nEstrogen-like actions: Fasting GH increased from 0.096 to 0.23 μg/L (p=0.033), IGFBP-3 increased from 3.6 to 4.0 mg/L (p=0.041). FUL potentiated GH responses to L-arginine/saline (p=0.007), L-arginine/ghrelin (p=0.008), and L-arginine/GHRH+ghrelin (p=0.031), but not L-arginine/GHRH alone.\n\nAnti-estrogen actions: Prolactin decreased from 7.1 to 5.5 μg/L (p=0.05), IGFBP-1 decreased from 44 to 27 μg/L (p=0.048).\n\nNeutral effects: Testosterone, estradiol, estrone, SHBG, IGF-I, LH, and FSH were unaffected.","whyItMatters":"This study reveals unexpected complexity in how estrogen receptor antagonists interact with peptide-driven GH secretion. Understanding these interactions is important for managing GH deficiency in aging women and for interpreting the effects of antiestrogen treatments (like those used in breast cancer) on the growth hormone axis. The finding that fulvestrant acts as an estrogen agonist on GH challenges simple models of estrogen receptor pharmacology.","specificNumbers":"","methodology":"Randomized, double-blind, placebo-controlled, parallel-cohort study at the Mayo Center. 24 postmenopausal women (ages 50-77, BMI 19-32) received either placebo (n=14) or fulvestrant (n=10) for 3 weeks, followed by infusions of L-arginine combined with saline, GHRH, ghrelin, or both peptide secretagogues. GH was sampled every 10 minutes over 6 hours. Sex steroids were measured by mass spectrometry.","limitations":"The sample size was small (24 participants, only 10 receiving fulvestrant). The study was 3 weeks long, which may not capture longer-term effects. The mechanism by which fulvestrant acts as an estrogen agonist on GH secretion is not fully explained. The postmenopausal population studied may not represent premenopausal women or men. The doses and clinical relevance of the peptide secretagogue infusions may differ from physiological conditions."},{"rthcId":"RPEP-02532","title":"Neonatal injury rapidly alters markers of pain and stress in rat pups.","authors":"Victoria, Nicole C; Karom, Mary C; Eichenbaum, Hila; Murphy, Anne Z","year":2014,"journal":"Developmental neurobiology, 74(1), 42-51","doi":"10.1002/dneu.22129","pmid":"24022912","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02533","title":"Topical administration of lacritin is a novel therapy for aqueous-deficient dry eye disease.","authors":"Vijmasi, Trinka; Chen, Feeling Y T; Balasubbu, Suganthalakshmi; Gallup, Marianne; McKown, Robert L; Laurie, Gordon W; McNamara, Nancy A","year":2014,"journal":"Investigative ophthalmology & visual science, 55(8), 5401-9","doi":"10.1167/iovs.14-13924","pmid":"25034600","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02534","title":"Bioactive peptides derived from human milk proteins--mechanisms of action.","authors":"Wada, Yasuaki; Lönnerdal, Bo","year":2014,"journal":"The Journal of nutritional biochemistry, 25(5), 503-14","doi":"10.1016/j.jnutbio.2013.10.012","pmid":"24411973","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02535","title":"Designer self-assembling peptide nanofiber scaffolds containing link protein N-terminal peptide induce chondrogenesis of rabbit bone marrow stem cells.","authors":"Wang, Baichuan; Sun, Caixia; Shao, Zengwu; Yang, Shuhua; Che, Biao; Wu, Qiang; Liu, Jianxiang","year":2014,"journal":"BioMed research international, 2014, 421954","doi":"10.1155/2014/421954","pmid":"25243141","tags":[],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"A functionalized self-assembling peptide nanofiber scaffold containing link protein N-terminal peptide (link N) significantly promoted bone marrow stem cell (BMSC) adhesion and stimulated the production of type II collagen and aggrecan — the two key structural molecules of cartilage-like tissue found in spinal discs.\n\nThe functionalized scaffold (LN-NS, built on the RADA16 self-assembling peptide platform) outperformed the plain RADA16 scaffold in cell adhesion and cartilage matrix production, though it did not increase BMSC proliferation. This suggests the link N peptide directs stem cells toward a cartilage-producing phenotype (chondrogenesis) rather than simply making them multiply faster.","whyItMatters":"Degenerative disc disease affects millions and has no regenerative treatment. The nucleus pulposus — the gel-like center of spinal discs — deteriorates with age, and replacing it requires both a structural scaffold and biological signals to tell cells what to make. This self-assembling peptide scaffold provides both: a 3D structure for cells to grow in and a link N peptide signal that drives cartilage matrix production from stem cells, offering a potential injectable therapy for disc regeneration.","specificNumbers":"RADA16 peptide base scaffold · Link N peptide functionalization · Significantly increased BMSC adhesion · Increased type II collagen biosynthesis · Increased aggrecan deposition · No proliferation increase","methodology":"Researchers created a functionalized self-assembling peptide hydrogel by incorporating the N-terminal peptide sequence of link protein into the RADA16 nanofiber scaffold. Rabbit bone marrow stem cells were cultured on the functionalized scaffold and compared to the plain RADA16 scaffold. Cell adhesion, proliferation, and biosynthesis of type II collagen and aggrecan were measured.","limitations":"This is an in vitro study — cells on scaffolds in a lab, not in living spinal discs. Rabbit BMSCs may behave differently from human cells. The study didn't test the scaffold in an animal disc degeneration model. Mechanical properties under spinal loading conditions were not assessed. Long-term stability of the peptide scaffold and sustained chondrogenic activity are unknown."},{"rthcId":"RPEP-02536","title":"Rational design and synthesis of an orally bioavailable peptide guided by NMR amide temperature coefficients.","authors":"Wang, Conan K; Northfield, Susan E; Colless, Barbara; Chaousis, Stephanie; Hamernig, Ingrid; Lohman, Rink-Jan; Nielsen, Daniel S; Schroeder, Christina I; Liras, Spiros; Price, David A; Fairlie, David P; Craik, David J","year":2014,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 111(49), 17504-9","doi":null,"pmid":"25416591","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The researchers used NMR temperature coefficients to rapidly identify exposed amide bonds in cyclic peptides — the spots most vulnerable to water and therefore most in need of protection. By selectively N-methylating these positions, they created peptides with improved membrane permeability.\n\nFive leucine-rich peptide scaffolds were tested with various N-methylation patterns. The most promising derivative (peptide 15) achieved 33% oral bioavailability in a rat model, validated through in vivo testing. The approach was further validated by explaining the known oral bioavailability of a somatostatin analog. Membrane permeability was confirmed using both parallel artificial membrane permeability assay (PAMPA) and Caco-2 cell assays before moving to animal testing.","whyItMatters":"Most peptide drugs today require injection because they can't survive oral administration. If peptides could be taken as pills, it would transform treatment for conditions like diabetes, growth disorders, and many others. This study provides a faster, more practical method for designing orally available peptides than the traditional approach of solving full 3D structures — potentially accelerating the development of oral peptide therapeutics across the pharmaceutical industry.","specificNumbers":"","methodology":"The team used NMR spectroscopy to measure temperature coefficients of amide protons in cyclic peptides, which reveals which amide bonds are solvent-exposed versus shielded by intramolecular hydrogen bonds. Exposed amides were selectively N-methylated to reduce water interaction and improve membrane crossing. Membrane permeability was assessed in vitro using PAMPA and Caco-2 cell assays. The top candidate was then tested in vivo in a Wistar rat model to measure actual oral bioavailability.","limitations":"The 33% oral bioavailability was demonstrated in rats, which may not directly translate to humans due to differences in gut physiology and metabolism. The peptide scaffolds tested were leucine-rich model peptides without therapeutic targets — applying this approach to bioactive peptides with specific targets could introduce additional constraints. The study focused on membrane permeability as the main barrier to oral availability, but enzymatic degradation and first-pass metabolism are also important factors not fully addressed."},{"rthcId":"RPEP-02537","title":"Increasing substance P levels in serum and synovial tissues from patients with developmental dysplasia of the hip (DDH).","authors":"Wang, Hui; Zheng, Xin-Feng; Zhang, Xiang; Li, Zheng; Shen, Chao; Zhu, Jun-Feng; Cui, Yi-Min; Chen, Xiao-Dong","year":2014,"journal":"BMC musculoskeletal disorders, 15, 92","doi":"10.1186/1471-2474-15-92","pmid":"24642234","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02538","title":"Substance P exacerbates dopaminergic neurodegeneration through neurokinin-1 receptor-independent activation of microglial NADPH oxidase.","authors":"Wang, Qingshan; Chu, Chun-Hsien; Qian, Li; Chen, Shih-Heng; Wilson, Belinda; Oyarzabal, Esteban; Jiang, Lulu; Ali, Syed; Robinson, Bonnie; Kim, Hyoung-Chun; Hong, Jau-Shyong","year":2014,"journal":"The Journal of neuroscience : the official journal of the Society for Neuroscience, 34(37), 12490-503","doi":"10.1523/JNEUROSCI.2238-14.2014","pmid":"25209287","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02539","title":"Highly lipophilic 3-epi-betulinic acid derivatives as potent and selective TGR5 agonists with improved cellular efficacy.","authors":"Wang, Xiao-yin; Zhang, Shu-yong; Li, Jing; Liu, Hua-nan; Xie, Xin; Nan, Fa-jun","year":2014,"journal":"Acta pharmacologica Sinica, 35(11), 1463-72","doi":"10.1038/aps.2014.97","pmid":"25283506","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02540","title":"Evaluation of ghrelin level and appetite regulation in patients with acute exacerbations of chronic obstructive pulmonary disease.","authors":"Wang, Ye; Shen, Yongchun; Zuo, Qiunan; Zhao, Li; Wan, Chun; Tian, Panwen; Chen, Lei; Wen, Fuqiang","year":2014,"journal":"International journal of chronic obstructive pulmonary disease, 9, 863-70","doi":"10.2147/COPD.S65195","pmid":"25152618","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02541","title":"CXCL10 controls inflammatory pain via opioid peptide-containing macrophages in electroacupuncture.","authors":"Wang, Ying; Gehringer, Rebekka; Mousa, Shaaban A; Hackel, Dagmar; Brack, Alexander; Rittner, Heike L","year":2014,"journal":"PloS one, 9(4), e94696","doi":"10.1371/journal.pone.0094696","pmid":"24732949","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02542","title":"Mitigation of sociocommunicational deficits of autism through oxytocin-induced recovery of medial prefrontal activity: a randomized trial.","authors":"Watanabe, Takamitsu; Abe, Osamu; Kuwabara, Hitoshi; Yahata, Noriaki; Takano, Yosuke; Iwashiro, Norichika; Natsubori, Tatsunobu; Aoki, Yuta; Takao, Hidemasa; Kawakubo, Yuki; Kamio, Yoko; Kato, Nobumasa; Miyashita, Yasushi; Kasai, Kiyoto; Yamasue, Hidenori","year":2014,"journal":"JAMA psychiatry, 71(2), 166-75","doi":"10.1001/jamapsychiatry.2013.3181","pmid":"24352377","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02543","title":"Investigation of PACAP Fragments and Related Peptides in Chronic Retinal Hypoperfusion.","authors":"Werling, Dora; Reglodi, Dora; Kiss, Peter; Toth, Gabor; Szabadfi, Krisztina; Tamas, Andrea; Biro, Zsolt; Atlasz, Tamas","year":2014,"journal":"Journal of ophthalmology, 2014, 563812","doi":"10.1155/2014/563812","pmid":"24900914","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02544","title":"The anatomy of osteoarthritic joint pain.","authors":"Witt, Kevin L; Vilensky, Joel A","year":2014,"journal":"Clinical anatomy (New York, N.Y.), 27(3), 451-4","doi":"10.1002/ca.22120","pmid":"22730047","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Nociceptive free-nerve endings and substance P-staining nerve fibers were identified in multiple joint structures: accessory ligaments, synovium (joint lining), subchondral bone (bone beneath cartilage), menisci, and periosteum (bone covering). Calcitonin gene-related peptide (CGRP) was also present in these tissues.\n\nThe vasculature may contribute to pain through vasospasm or ischemia, though this mechanism remains unproven. Joint denervation procedures can relieve pain — confirming that articular nerves carry pain signals — but cannot pinpoint the specific tissue source. The review concludes that the primary anatomical source of OA pain remains unclear and likely varies between patients and joints.","whyItMatters":"Osteoarthritis affects over 500 million people worldwide, and pain management is often inadequate because treatments aren't targeted at the specific tissue source generating pain. Understanding where neuropeptides like substance P and CGRP are concentrated in joint tissues could lead to more precise pain treatments — for example, targeted nerve blocks, localized anti-CGRP therapies, or tissue-specific interventions rather than systemic painkillers.","specificNumbers":"","methodology":"This is a narrative review focused on studies examining nociceptive innervation of synovial joints, with particular emphasis on the distribution of substance P and calcitonin gene-related peptide in joint tissues. The review was written for educational purposes, aimed at improving the teaching of pain anatomy in medical school courses.","limitations":"This is a narrative review for teaching purposes, not a systematic review with comprehensive literature search methodology. It was published in 2014 and may not reflect more recent research on joint nociception. The review acknowledges that the primary pain source in OA remains unidentified, limiting its ability to provide definitive conclusions. Individual variation in pain sources adds complexity that cannot be resolved by anatomical mapping alone."},{"rthcId":"RPEP-02545","title":"A study of effects of peptide fragments of bovine and human lactoferrins on activities of three key HIV-1 enzymes.","authors":"Wong, Jack Ho; Liu, Zhaokun; Law, Kenneth Wai Kit; Liu, Fang; Xia, Lixin; Wan, David Chi Cheong; Ng, Tzi Bun","year":2014,"journal":"Peptides, 62, 183-8","doi":null,"pmid":"25445609","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02546","title":"Comparison of anorectic and emetic potencies of deoxynivalenol (vomitoxin) to the plant metabolite deoxynivalenol-3-glucoside and synthetic deoxynivalenol derivatives EN139528 and EN139544.","authors":"Wu, Wenda; Zhou, Hui-Ren; Bursian, Steven J; Pan, Xiao; Link, Jane E; Berthiller, Franz; Adam, Gerhard; Krantis, Anthony; Durst, Tony; Pestka, James J","year":2014,"journal":"Toxicological sciences : an official journal of the Society of Toxicology, 142(1), 167-81","doi":"10.1093/toxsci/kfu166","pmid":"25173790","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02547","title":"Mechanism of action of the tri-hybrid antimicrobial peptide LHP7 from lactoferricin, HP and plectasin on Staphylococcus aureus.","authors":"Xi, Di; Wang, Xiumin; Teng, Da; Mao, Ruoyu","year":2014,"journal":"Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine, 27(5), 957-68","doi":"10.1007/s10534-014-9768-x","pmid":"25015218","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02548","title":"Combination therapy with thymosin alpha1 and dexamethasone helps mice survive sepsis.","authors":"Xiang, Xiao-song; Li, Ning; Zhao, Yun-zhao; Li, Qiu-rong; Li, Jie-shou","year":2014,"journal":"Inflammation, 37(2), 402-16","doi":"10.1007/s10753-013-9753-5","pmid":"24122349","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among five treatment groups, mice receiving the combination of dexamethasone (DXM) and thymosin alpha-1 (Tα1) timed to dendritic cell number changes had the highest survival rate. Tα1 increased dendritic cell numbers in vivo while DXM reduced them — when combined in a timed approach, they normalized DC numbers during endotoxemia. The combination therapy decreased bacterial translocation to extra-intestinal organs and enhanced clearance of secondary infections. Neither drug alone significantly changed DC capacity to activate T cells or expression of MHCII/CD86.","whyItMatters":"Sepsis remains one of the leading causes of death in intensive care units, and immune dysfunction — not just the initial infection — drives mortality. This study demonstrates that intelligently combining an immune-boosting peptide with an anti-inflammatory steroid, timed to the patient's immune state, could be more effective than either alone. The concept of timing immunotherapy to immune cell dynamics is a sophisticated approach that could inform clinical sepsis management.","specificNumbers":"","methodology":"Endotoxemic BALB/c mice were randomly divided into five treatment groups receiving different combinations and timing of dexamethasone and thymosin alpha-1. Researchers measured dendritic cell numbers, MHCII and CD86 expression, T cell activation capacity, survival rates, TNF-α and IL-10 cytokine levels, bacterial translocation to organs, and secondary infection clearance. Both in vitro and in vivo assessments were performed.","limitations":"This is a mouse endotoxemia model, which simplifies the complex pathophysiology of human sepsis. The number of animals per group and specific survival rates were not detailed in the abstract. Endotoxemia models use a single bacterial toxin rather than actual polymicrobial infection. The timing of therapy based on DC numbers, while conceptually elegant, would be difficult to implement clinically without rapid DC monitoring tools. Long-term outcomes beyond survival were not assessed."},{"rthcId":"RPEP-02549","title":"Ghrelin signalling in β-cells regulates insulin secretion and blood glucose.","authors":"Yada, T; Damdindorj, B; Rita, R S; Kurashina, T; Ando, A; Taguchi, M; Koizumi, M; Sone, H; Nakata, M; Kakei, M; Dezaki, K","year":2014,"journal":"Diabetes, obesity & metabolism, 16 Suppl 1, 111-7","doi":"10.1111/dom.12344","pmid":"25200304","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02550","title":"Distribution of substance P and the calcitonin gene-related peptide in the human tensor tympani muscle.","authors":"Yamazaki, Masahiko; Sato, Iwao","year":2014,"journal":"European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery, 271(5), 905-11","doi":"10.1007/s00405-013-2469-1","pmid":"23568041","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02551","title":"Amylin in vasodilation, energy expenditure and inflammation.","authors":"Yang, Fan","year":2014,"journal":"Frontiers in bioscience (Landmark edition), 19(6), 936-44","doi":null,"pmid":"24896327","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02552","title":"Recent studies on the antimicrobial peptides lactoferricin and lactoferrampin.","authors":"Yin, C; Wong, J H; Ng, T B","year":2014,"journal":"Current molecular medicine, 14(9), 1139-54","doi":null,"pmid":"25324002","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02553","title":"Effect of 1440-nanometer neodymium:yttrium-aluminum-garnet laser irradiation on pain and neuropeptide reduction: a randomized prospective clinical trial.","authors":"Yoo, Yeon-Jee; Shon, Won-Jun; Baek, Seung-Ho; Kang, Mo K; Kim, Hyeon-Cheol; Lee, WooCheol","year":2014,"journal":"Journal of endodontics, 40(1), 28-32","doi":"10.1016/j.joen.2013.07.011","pmid":"24331986","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02554","title":"Differential effects of laparoscopic sleeve gastrectomy and laparoscopic gastric bypass on appetite, circulating acyl-ghrelin, peptide YY3-36 and active GLP-1 levels in non-diabetic humans.","authors":"Yousseif, Ahmed; Emmanuel, Julian; Karra, Efthimia; Millet, Queensta; Elkalaawy, Mohamed; Jenkinson, Andrew D; Hashemi, Majid; Adamo, Marco; Finer, Nicholas; Fiennes, Alberic G; Withers, Dominic J; Batterham, Rachel L","year":2014,"journal":"Obesity surgery, 24(2), 241-52","doi":"10.1007/s11695-013-1066-0","pmid":"23996294","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02555","title":"In vivo regulation of NGF-mediated functions by Nedd4-2 ubiquitination of TrkA.","authors":"Yu, Tao; Calvo, Laura; Anta, Begoña; López-Benito, Saray; López-Bellido, Roger; Vicente-García, Cristina; Tessarollo, Lino; Rodriguez, Raquel E; Arévalo, Juan C","year":2014,"journal":"The Journal of neuroscience : the official journal of the Society for Neuroscience, 34(17), 6098-106","doi":"10.1523/JNEUROSCI.4271-13.2014","pmid":"24760869","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02556","title":"Expression of ghrelin and its receptor in rats after coronary artery ligation.","authors":"Yuan, Ming-Jie; Huang, He; Quan, Li; Tang, Yan-Hong; Wang, Xi; Jiang, Hong; Huang, Cong-Xin","year":2014,"journal":"Regulatory peptides, 192-193, 1-5","doi":"10.1016/j.regpep.2014.07.001","pmid":"25058156","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02557","title":"Ghrelin receptor agonist, GHRP-2, produces antinociceptive effects at the supraspinal level via the opioid receptor in mice.","authors":"Zeng, Ping; Li, Shu; Zheng, Yue-hui; Liu, Fu-Yan; Wang, Jing-lei; Zhang, Da-lei; Wei, Jie","year":2014,"journal":"Peptides, 55, 103-9","doi":"10.1016/j.peptides.2014.02.013","pmid":"24607724","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02558","title":"Evaluation of 99mTc-peptide-ZHER2:342 Affibody® molecule for in vivo molecular imaging.","authors":"Zhang, J-M; Zhao, X-M; Wang, S-J; Ren, X-C; Wang, N; Han, J-Y; Jia, L-Z","year":2014,"journal":"The British journal of radiology, 87(1033), 20130484","doi":"10.1259/bjr.20130484","pmid":"24273251","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The 99mTc-peptide-ZHER2:342 molecular probe was successfully synthesized and labeled with technetium-99m at 98.10 ± 1.73% efficiency. The probe remained highly stable in vitro and showed clear selective imaging: HER2-expressing SKOV-3 tumor xenografts showed high uptake and were clearly visible, while HER2-low MDA-MB-231 xenografts were not detectable at any time point after injection.\n\nThe predominant clearance pathway was renal (through the kidneys), which is favorable for imaging because it reduces background signal in the abdomen and allows cleaner tumor visualization.","whyItMatters":"Knowing whether a tumor is HER2-positive is critical for selecting the right cancer treatment, but current methods typically require a tissue biopsy. A non-invasive imaging probe that can detect HER2 status throughout the body could revolutionize cancer diagnosis and treatment monitoring — allowing doctors to see HER2 expression in real time without surgery, and potentially detecting metastases that biopsies would miss.","specificNumbers":"","methodology":"The ZHER2:342 Affibody molecule was synthesized using solid-phase peptide synthesis (Fmoc/tBu chemistry). A chelating peptide sequence (Gly-(d)Ala-Gly-Gly) was attached to enable technetium-99m labeling. Labeling efficiency and stability were assessed by reversed-phase HPLC. Biodistribution and imaging studies were performed in nude mice bearing either HER2-positive (SKOV-3) or HER2-negative (MDA-MB-231) tumor xenografts.","limitations":"This is a preclinical study in nude mice with implanted human tumor xenografts, which does not fully replicate human cancer biology. Only two cell lines were tested (one HER2-positive, one HER2-negative). The study did not assess imaging in the presence of more complex anatomical structures or in larger animals. Translation to human clinical use would require extensive further development including toxicity studies and regulatory approval."},{"rthcId":"RPEP-02559","title":"Multicomponent diversity-oriented synthesis of aza-lysine-peptide mimics.","authors":"Zhang, Jinqiang; Proulx, Caroline; Tomberg, Anna; Lubell, William D","year":2014,"journal":"Organic letters, 16(1), 298-301","doi":"10.1021/ol403297v","pmid":"24328523","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02560","title":"Activation of glucagon-like peptide-1 receptor inhibits growth and promotes apoptosis of human pancreatic cancer cells in a cAMP-dependent manner.","authors":"Zhao, Hejun; Wei, Rui; Wang, Liang; Tian, Qing; Tao, Ming; Ke, Jing; Liu, Ye; Hou, Wenfang; Zhang, Lin; Yang, Jin; Hong, Tianpei","year":2014,"journal":"American journal of physiology. Endocrinology and metabolism, 306(12), E1431-41","doi":"10.1152/ajpendo.00017.2014","pmid":"24801389","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02561","title":"Activation of growth hormone secretagogue receptor induces time-dependent clock phase delay in mice.","authors":"Zhou, Lan; Gao, Qian; Zhang, Peng; Guo, Shu; Gu, Jingli; Hao, Wei; Cao, Ji-Min","year":2014,"journal":"American journal of physiology. Endocrinology and metabolism, 307(6), E515-26","doi":"10.1152/ajpendo.00535.2013","pmid":"25074983","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02562","title":"The medio-basal hypothalamus as a dynamic and plastic reproduction-related kisspeptin-gnrh-pituitary center in fish.","authors":"Zmora, Nilli; Stubblefield, John; Golan, Matan; Servili, Arianna; Levavi-Sivan, Berta; Zohar, Yonathan","year":2014,"journal":"Endocrinology, 155(5), 1874-86","doi":"10.1210/en.2013-1894","pmid":"24484170","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02563","title":"Biocompatibility of functionalized designer self-assembling nanofiber scaffolds containing FRM motif for neural stem cells.","authors":"Zou, Zhenwei; Liu, Ting; Li, JingFeng; Li, Pindong; Ding, Qian; Peng, Gang; Zheng, Qixin; Zeng, Xianlin; Wu, Yongchao; Guo, Xiaodong","year":2014,"journal":"Journal of biomedical materials research. Part A, 102(5), 1286-93","doi":"10.1002/jbm.a.34804","pmid":"23703883","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02564","title":"N-acylated peptides derived from human lactoferricin perturb organization of cardiolipin and phosphatidylethanolamine in cell membranes and induce defects in Escherichia coli cell division.","authors":"Zweytick, Dagmar; Japelj, Bostjan; Mileykovskaya, Eugenia; Zorko, Mateja; Dowhan, William; Blondelle, Sylvie E; Riedl, Sabrina; Jerala, Roman; Lohner, Karl","year":2014,"journal":"PloS one, 9(3), e90228","doi":"10.1371/journal.pone.0090228","pmid":"24595074","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02565","title":"Melanocortin receptor agonists in the treatment of male and female sexual dysfunctions: results from basic research and clinical studies.","authors":"Ückert, Stefan; Bannowsky, Andreas; Albrecht, Knut; Kuczyk, Markus A","year":2014,"journal":"Expert opinion on investigational drugs, 23(11), 1477-83","doi":"10.1517/13543784.2014.934805","pmid":"25096243","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Clinical development of three melanocortin receptor (MCR) agonist peptides has advanced understanding of how the melanocortin pathway regulates sexual function. Melanotan I, melanotan II, and bremelanotide have been studied for treating erectile dysfunction in males and sexual arousal and orgasmic disorders in females.\n\nUnlike phosphodiesterase-5 inhibitors (e.g., sildenafil/Viagra) that act peripherally on nitric oxide/cyclic GMP signaling in genital smooth muscle, MCR agonists target central nervous system pathways involved in mediating arousal and orgasm. The available data support the role of melanocortin pathway activation in regulating both male and female sexual functions, warranting further clinical investigation.","whyItMatters":"Sexual dysfunction affects millions of people, and current treatments have significant limitations. PDE5 inhibitors work for many men with ED but don't address desire or arousal, and no comparable options existed for women until recently. Melanocortin peptide agonists represent a fundamentally different therapeutic mechanism — targeting brain circuits that control sexual motivation and arousal rather than just genital blood flow. Bremelanotide was eventually FDA-approved in 2019 for female hypoactive sexual desire disorder, validating this peptide-based approach.","specificNumbers":"","methodology":"Narrative review summarizing basic research and clinical study results for melanocortin receptor agonist peptides (melanotan I, melanotan II, bremelanotide) in the treatment of male erectile dysfunction and female sexual arousal and orgasmic disorders.","limitations":"The review was published in 2014 and does not include the final clinical trial results that led to bremelanotide's FDA approval in 2019. Melanotan I and II were associated with side effects including nausea and skin darkening (due to melanocyte stimulation) that complicated their clinical development. The central mechanism of action raises questions about potential CNS side effects with long-term use. The exact melanocortin receptor subtypes mediating sexual effects were not fully characterized at the time of this review."},{"rthcId":"RPEP-02566","title":"Anderson 2015 Ox2r Ethanol Preferring Rats","authors":"","year":2015,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02567","title":"Ashapkin 2015 Epigenetic Mechanisms Of Peptidergic","authors":"","year":2015,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02568","title":"Gauthier 2015 Cerebrolysin Alzheimers Meta Analysis","authors":"","year":2015,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02569","title":"Lambert 2015 Adc Technology Progress Challenges","authors":"","year":2015,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02570","title":"Martin Ruiz 2015 Comparison Telomere Methods","authors":"","year":2015,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02571","title":"Vasoactive intestinal peptide-deficient mice exhibit reduced pathology in trinitrobenzene sulfonic acid-induced colitis.","authors":"Abad, Catalina; Cheung-Lau, Gardenia; Coûté-Monvoisin, Anne-Claire; Waschek, James A","year":2015,"journal":"Neuroimmunomodulation, 22(3), 203-12","doi":"10.1159/000364912","pmid":"25301381","tags":["neuropeptides","inflammation-immunology"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"When TNBS-induced colitis (a model for Crohn's disease) was triggered in VIP knockout mice, they showed a milder clinical profile compared to wild-type mice. Serum levels of TNF-α and IL-6 were lower in VIP-deficient mice. However, colon histopathological scores and local cytokine levels did not differ between the groups, indicating that VIP's absence selectively disrupted certain but not all immunological compartments.\n\nInterestingly, splenocytes from TNBS-treated VIP knockout mice showed enhanced proliferative responses to T cell stimulation (anti-CD3/CD28), suggesting that while some immune functions were dampened, T cell reactivity was actually increased. This pattern — reduced clinical disease but enhanced T cell responses — mirrors findings in VIP knockout mice with endotoxemia and autoimmune encephalomyelitis.","whyItMatters":"VIP has been investigated as a potential therapy for inflammatory bowel disease based on decades of research showing it reduces inflammation when injected. This study complicates that narrative by showing that the body's own VIP isn't simply protective — its chronic absence actually makes some aspects of colitis less severe. This is important for anyone developing VIP-based therapies, because the relationship between endogenous VIP signaling and gut inflammation is not the straightforward anti-inflammatory story that was assumed.","specificNumbers":"Lower TNF-α and IL-6 in VIP KO mice; enhanced splenocyte proliferative response to anti-CD3/CD28 in VIP KO mice","methodology":"Researchers administered TNBS (a chemical that induces colitis resembling Crohn's disease) intracolonically to both VIP knockout mice and wild-type controls. They tracked weight loss and disease severity over time, analyzed colon tissue for damage and immune cell infiltration (myeloperoxidase activity), measured TNF-α and IL-6 in both colon tissue and blood, and tested how well spleen immune cells from treated mice responded to T cell stimulation in the lab.","limitations":"The study used constitutive VIP knockout mice, meaning VIP was absent from birth. This chronic absence may have caused compensatory changes in the immune system that wouldn't occur with acute VIP manipulation. The TNBS colitis model is a chemical model that doesn't fully replicate human Crohn's disease. Not all parameters showed differences — histopathological scores were similar between groups — suggesting the milder phenotype was selective rather than comprehensive."},{"rthcId":"RPEP-02572","title":"Efficacy of Kisspeptin-54 to Trigger Oocyte Maturation in Women at High Risk of Ovarian Hyperstimulation Syndrome (OHSS) During In Vitro Fertilization (IVF) Therapy.","authors":"Abbara, Ali; Jayasena, Channa N; Christopoulos, Georgios; Narayanaswamy, Shakunthala; Izzi-Engbeaya, Chioma; Nijher, Gurjinder M K; Comninos, Alexander N; Peters, Deborah; Buckley, Adam; Ratnasabapathy, Risheka; Prague, Julia K; Salim, Rehan; Lavery, Stuart A; Bloom, Stephen R; Szigeti, Matyas; Ashby, Deborah A; Trew, Geoffrey H; Dhillo, Waljit S","year":2015,"journal":"The Journal of clinical endocrinology and metabolism, 100(9), 3322-31","doi":"10.1210/jc.2015-2332","pmid":"26192876","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02573","title":"Review peptide-targeted liposomes for selective drug delivery: Advantages and problematic issues.","authors":"Accardo, Antonella; Morelli, Giancarlo","year":2015,"journal":"Biopolymers, 104(5), 462-79","doi":"10.1002/bip.22678","pmid":"26010528","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02574","title":"Quantitative gastrointestinal and psychological traits associated with obesity and response to weight-loss therapy.","authors":"Acosta, Andres; Camilleri, Michael; Shin, Andrea; Vazquez-Roque, Maria I; Iturrino, Johanna; Burton, Duane; O'Neill, Jessica; Eckert, Deborah; Zinsmeister, Alan R","year":2015,"journal":"Gastroenterology, 148(3), 537-546.e4","doi":"10.1053/j.gastro.2014.11.020","pmid":"25486131","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02575","title":"Identification of potent antioxidant bioactive peptides from goat milk proteins.","authors":"Ahmed, Ahmed S; El-Bassiony, Tawfik; Elmalt, Laila M; Ibrahim, Hisham R","year":2015,"journal":"Food research international (Ottawa, Ont.), 74, 80-88","doi":"10.1016/j.foodres.2015.04.032","pmid":"28412006","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02576","title":"Oxytocin's neurochemical effects in the medial prefrontal cortex underlie recovery of task-specific brain activity in autism: a randomized controlled trial.","authors":"Aoki, Y; Watanabe, T; Abe, O; Kuwabara, H; Yahata, N; Takano, Y; Iwashiro, N; Natsubori, T; Takao, H; Kawakubo, Y; Kasai, K; Yamasue, H","year":2015,"journal":"Molecular psychiatry, 20(4), 447-53","doi":"10.1038/mp.2014.74","pmid":"25070538","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02577","title":"Oxytocin increases eye contact during a real-time, naturalistic social interaction in males with and without autism.","authors":"Auyeung, B; Lombardo, M V; Heinrichs, M; Chakrabarti, B; Sule, A; Deakin, J B; Bethlehem, R A I; Dickens, L; Mooney, N; Sipple, J A N; Thiemann, P; Baron-Cohen, S","year":2015,"journal":"Translational psychiatry, 5(2), e507","doi":"10.1038/tp.2014.146","pmid":"25668435","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02578","title":"Incretin-based drugs and adverse pancreatic events: almost a decade later and uncertainty remains.","authors":"Azoulay, Laurent","year":2015,"journal":"Diabetes care, 38(6), 951-3","doi":"10.2337/dc15-0347","pmid":"25998285","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02579","title":"Effect of Oxyntomodulin, Glucagon, GLP-1, and Combined Glucagon +GLP-1 Infusion on Food Intake, Appetite, and Resting Energy Expenditure.","authors":"Bagger, Jonatan Ising; Holst, Jens Juul; Hartmann, Bolette; Andersen, Birgitte; Knop, Filip Krag; Vilsbøll, Tina","year":2015,"journal":"The Journal of clinical endocrinology and metabolism, 100(12), 4541-52","doi":"10.1210/jc.2015-2335","pmid":"26445112","tags":[],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"In a rigorous head-to-head comparison, oxyntomodulin, GLP-1, glucagon, and GLP-1+glucagon combined all reduced food intake by similar amounts compared to saline (roughly 15-17% reduction). However, combining GLP-1 and glucagon together did not produce an additive effect — the combination was no better than either peptide alone.\n\nThe mechanisms differed: oxyntomodulin, GLP-1, and GLP-1+glucagon slowed gastric emptying and reduced appetite scores, while glucagon reduced food intake without affecting either gastric emptying or appetite. No peptide infusion significantly changed resting energy expenditure compared to saline.","whyItMatters":"Oxyntomodulin activates both GLP-1 and glucagon receptors, and the drug industry has bet heavily on dual-agonists (like survodutide) that mimic this. This study challenges a key assumption: that activating both receptors simultaneously produces additive benefits. The finding that GLP-1+glucagon was no better than either alone at reducing food intake suggests oxyntomodulin's weight-loss mechanism may not be simply the sum of its receptor activities — there may be something else at play.","specificNumbers":"n=15 healthy males · Age 22 (18-32) · BMI 23 (21-26) · GLP-1: 1 pmol/kg/min · Glucagon: 0.86 pmol/kg/min · Oxyntomodulin: 3 pmol/kg/min · Food intake (g): saline 811, GLP-1 669, glucagon 686, OXM 689, GLP-1+glucagon 688 · No REE changes","methodology":"Double-blinded, randomized, crossover study in 15 healthy young men. Each participant received five 4-hour liquid meal tests during infusion of saline, GLP-1, glucagon, oxyntomodulin, or GLP-1+glucagon on separate occasions. Researchers measured resting energy expenditure (oxygen uptake), gastric emptying, composite appetite scores, and ad libitum food intake.","limitations":"Small sample size (n=15) of only young, lean, healthy men — results may differ in obese individuals or women. Acute infusion study (4 hours) may not reflect chronic effects relevant to weight management. The doses tested may not have been optimal to demonstrate additive effects. Only one dose combination of GLP-1+glucagon was tested."},{"rthcId":"RPEP-02580","title":"Growth hormone-releasing hormone agonists reduce myocardial infarct scar in swine with subacute ischemic cardiomyopathy.","authors":"Bagno, Luiza L; Kanashiro-Takeuchi, Rosemeire M; Suncion, Viky Y; Golpanian, Samuel; Karantalis, Vasileios; Wolf, Ariel; Wang, Bo; Premer, Courtney; Balkan, Wayne; Rodriguez, Jose; Valdes, David; Rosado, Marcos; Block, Norman L; Goldstein, Peter; Morales, Azorides; Cai, Ren-Zhi; Sha, Wei; Schally, Andrew V; Hare, Joshua M","year":2015,"journal":"Journal of the American Heart Association, 4(4)","doi":"10.1161/JAHA.114.001464","pmid":"25827134","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02581","title":"Stress and opioids: role of opioids in modulating stress-related behavior and effect of stress on morphine conditioned place preference.","authors":"Bali, Anjana; Randhawa, Puneet Kaur; Jaggi, Amteshwar Singh","year":2015,"journal":"Neuroscience and biobehavioral reviews, 51, 138-50","doi":"10.1016/j.neubiorev.2014.12.018","pmid":"25636946","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02582","title":"Interactions of the opioid and cannabinoid systems in reward: Insights from knockout studies.","authors":"Befort, Katia","year":2015,"journal":"Frontiers in pharmacology, 6, 6","doi":"10.3389/fphar.2015.00006","pmid":"25698968","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review demonstrates that the endogenous opioid system — operating through mu, delta, and kappa receptors activated by peptide ligands (enkephalins, endorphins, and dynorphins) — and the endocannabinoid system share extensive overlap in brain reward circuitry. Both receptor families are G protein-coupled and expressed throughout reinforcement pathways.\n\nGenetic knockout studies in mice have been instrumental in dissecting the specific roles of each receptor and ligand in reward processing. The evidence points to significant functional interactions between these two systems, meaning manipulating one system can alter the other's effects on reward-related behavior.","whyItMatters":"Addiction remains one of the most challenging public health problems, and current treatments often target only one system at a time. Understanding how opioid peptides and cannabinoids interact in the reward circuit could lead to more effective combination therapies that address addiction through multiple pathways simultaneously.","specificNumbers":"","methodology":"This is a review article that synthesizes findings from studies using genetically modified (knockout) mice. The approach examines what happens to reward-related behaviors when specific genes for opioid receptors, opioid peptides, cannabinoid receptors, or endocannabinoid enzymes are deleted, allowing researchers to identify each component's contribution in living animals.","limitations":"As a review, this paper does not present new experimental data. The findings are based primarily on mouse knockout studies, which may not fully translate to human physiology. Knockout models can also produce compensatory changes during development that complicate interpretation. The abstract does not discuss specific quantitative outcomes from the reviewed studies."},{"rthcId":"RPEP-02583","title":"Blocking the ghrelin receptor type 1a in the rat brain impairs memory encoding.","authors":"Beheshti, Siamak; Shahrokhi, Shahrzad","year":2015,"journal":"Neuropeptides, 52, 97-102","doi":"10.1016/j.npep.2015.05.003","pmid":"26072187","tags":[],"studyType":"animal","evidenceStrength":"preliminary","keyFinding":"Blocking ghrelin receptors (GHS-R1a) in the rat brain with the peptide antagonist d-Lys-3-GHRP-6 impaired memory encoding in a dose-dependent manner. Post-training injection significantly decreased step-through latency, increased time spent in the dark compartment, and increased the number of entries into the dark compartment — all indicating impaired memory consolidation.\n\nPre-training injection also impaired memory acquisition, significantly increasing time in the dark compartment in a dose-dependent manner. These results demonstrate that ghrelin receptor signaling in the brain is involved in both the acquisition and consolidation stages of memory formation.","whyItMatters":"Ghrelin is known primarily as a hunger hormone, but this study adds to growing evidence that the ghrelin-GHSR signaling pathway plays an important role in cognitive function. Understanding how peptide hormones like ghrelin influence memory could lead to new therapeutic targets for memory disorders and provides insight into why metabolic status affects cognitive performance.","specificNumbers":"","methodology":"72 male Wistar rats (230-280g) were divided into 9 groups of 8. After stereotaxic surgery to implant cannulas in the right ventricle, rats received intracerebroventricular (i.c.v.) injections of the GHS-R1a antagonist d-Lys-3-GHRP-6 at various doses (0.2, 2, 20, and 80 nM/5μl) either 10 minutes before training (acquisition) or immediately after training (consolidation) in a passive avoidance task. Memory retrieval was tested 24 hours later. Controls received drug solvent.","limitations":"This is a rodent study using direct brain injection, which has limited clinical translatability. The passive avoidance task tests only one type of memory (fear-motivated learning). The study did not identify which specific brain regions mediate the effect. The 2015 publication date means more recent work may have advanced understanding of this pathway."},{"rthcId":"RPEP-02584","title":"Characterization of the aggregates formed by various bacterial lipopolysaccharides in solution and upon interaction with antimicrobial peptides.","authors":"Bello, Gianluca; Eriksson, Jonny; Terry, Ann; Edwards, Katarina; Lawrence, M Jayne; Barlow, David; Harvey, Richard D","year":2015,"journal":"Langmuir : the ACS journal of surfaces and colloids, 31(2), 741-51","doi":"10.1021/la503267k","pmid":"25514503","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02585","title":"Rationale, design, and baseline characteristics in Evaluation of LIXisenatide in Acute Coronary Syndrome, a long-term cardiovascular end point trial of lixisenatide versus placebo.","authors":"Bentley-Lewis, Rhonda; Aguilar, David; Riddle, Matthew C; Claggett, Brian; Diaz, Rafael; Dickstein, Kenneth; Gerstein, Hertzel C; Johnston, Peter; Køber, Lars V; Lawson, Francesca; Lewis, Eldrin F; Maggioni, Aldo P; McMurray, John J V; Ping, Lin; Probstfield, Jeffrey L; Solomon, Scott D; Tardif, Jean-Claude; Wu, Yujun; Pfeffer, Marc A","year":2015,"journal":"American heart journal, 169(5), 631-638.e7","doi":"10.1016/j.ahj.2015.02.002","pmid":"25965710","tags":[],"studyType":"rct","evidenceStrength":"strong","keyFinding":"The ELIXA trial enrolled 6,068 patients with type 2 diabetes and recent acute coronary syndrome across 49 countries to evaluate whether the GLP-1 receptor agonist peptide lixisenatide affects cardiovascular outcomes. This paper reports the study design and baseline characteristics: participants had a mean age of 60.3 years, mean BMI of 30.2, and average diabetes duration of 9.3 years. The qualifying event was myocardial infarction in 83% and unstable angina in 17%.\n\nELIXA was the first major cardiovascular outcomes trial of a GLP-1 receptor agonist, designed to evaluate both safety and potential cardiovascular benefit in a high-risk diabetic population.","whyItMatters":"This trial was pivotal for the GLP-1 receptor agonist drug class. Following FDA requirements for cardiovascular safety testing of diabetes drugs (post-rosiglitazone), ELIXA set the stage for understanding whether GLP-1 peptide therapies — now among the most prescribed medications worldwide — are safe or beneficial for the heart. The results of this and subsequent GLP-1 RA cardiovascular trials fundamentally shaped treatment guidelines for type 2 diabetes.","specificNumbers":"","methodology":"Randomized, double-blind, placebo-controlled, parallel-group, multicenter trial. 6,068 patients with T2DM and recent ACS were randomized to lixisenatide or placebo across 49 countries. Enrollment ran from July 2010 to August 2013. The primary endpoint was a composite of cardiovascular death, nonfatal MI, nonfatal stroke, or hospitalization for unstable angina. Safety data on hypoglycemia, pancreatitis, and malignancy were systematically collected.","limitations":"This is a design and baseline characteristics paper — it does not report outcomes. The study population is specifically high-risk (recent ACS), so findings may not generalize to lower-risk diabetic patients. As a trial of a single GLP-1 RA (lixisenatide), results cannot be assumed to apply to other agents in the class like semaglutide or liraglutide."},{"rthcId":"RPEP-02586","title":"Impact of the immunomodulating peptide thymosin alpha 1 on multiple myeloma and immune recovery after hematopoietic stem cell transplantation.","authors":"Binsfeld, Marilène; Hannon, Muriel; Otjacques, Eléonore; Humblet-Baron, Stéphanie; Baudoux, Etienne; Beguin, Yves; Baron, Frédéric; Caers, Jo","year":2015,"journal":"Cancer immunology, immunotherapy : CII, 64(8), 989-98","doi":"10.1007/s00262-015-1708-2","pmid":"25971542","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02587","title":"Plant-rich mixed meals based on Palaeolithic diet principles have a dramatic impact on incretin, peptide YY and satiety response, but show little effect on glucose and insulin homeostasis: an acute-effects randomised study.","authors":"Bligh, H Frances J; Godsland, Ian F; Frost, Gary; Hunter, Karl J; Murray, Peter; MacAulay, Katrina; Hyliands, Della; Talbot, Duncan C S; Casey, John; Mulder, Theo P J; Berry, Mark J","year":2015,"journal":"The British journal of nutrition, 113(4), 574-84","doi":"10.1017/S0007114514004012","pmid":"25661189","tags":[],"studyType":"rct","evidenceStrength":"low-moderate","keyFinding":"Palaeolithic-type meals (fish and plant-rich, high in fibre and phytonutrients) dramatically increased GLP-1 and PYY satiety hormones over 180 minutes compared to a WHO guideline reference meal (p=0.001 and p<0.001 respectively). Satiety scores were correspondingly higher. Surprisingly, these effects occurred even when the Palaeolithic meal was matched for energy, protein, fat, and carbohydrates with the reference meal — suggesting the food composition itself, not just macronutrient ratios, drives the gut hormone response.\n\nGIP (another incretin hormone) was significantly suppressed by the Palaeolithic meals. Blood glucose and insulin responses did not differ between meal types.","whyItMatters":"This study demonstrates that food quality — not just macronutrient quantities — can profoundly influence the gut peptide hormones that regulate appetite. The same calories from different foods produced dramatically different GLP-1 and PYY responses, offering a dietary strategy to naturally boost the same satiety hormones that weight loss drugs like semaglutide target.","specificNumbers":"3 meal types · 180 min monitoring · GLP-1 significantly increased (p=0.001 & p=0.011) · PYY increased (p<0.001 & p=0.003) · GIP suppressed · No glucose/insulin difference","methodology":"Randomized crossover trial in healthy subjects. Three meals were consumed on separate occasions: two Palaeolithic-type meals (PAL1 with higher protein/energy, PAL2 matched to reference for macros) and a WHO guideline reference meal. Plasma GLP-1, GIP, PYY, glucose, and insulin were measured over 180 minutes. Satiety was assessed using electronic visual analogue scales (EVAS).","limitations":"The sample size is not specified in the abstract, but crossover designs in this field typically use small numbers. Only acute (single meal) effects were measured — long-term dietary effects remain unknown. Only healthy subjects were studied; results may differ in people with obesity or diabetes. The specific food composition differences (fibre, phytonutrients) between meals make it difficult to pinpoint which components drove the hormonal differences."},{"rthcId":"RPEP-02588","title":"Thymosin β4: multiple functions in protection, repair and regeneration of the mammalian heart.","authors":"Bollini, Sveva; Riley, Paul R; Smart, Nicola","year":2015,"journal":"Expert opinion on biological therapy, 15 Suppl 1, S163-74","doi":"10.1517/14712598.2015.1022526","pmid":"26094634","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02589","title":"Cell-autonomous regulation of Mu-opioid receptor recycling by substance P.","authors":"Bowman, Shanna L; Soohoo, Amanda L; Shiwarski, Daniel J; Schulz, Stefan; Pradhan, Amynah A; Puthenveedu, Manojkumar A","year":2015,"journal":"Cell reports, 10(11), 1925-36","doi":null,"pmid":"25801029","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02590","title":"WT1 vaccination in AML and MDS: A pilot trial with synthetic analog peptides.","authors":"Brayer, Jason; Lancet, Jeffrey E; Powers, John; List, Alan; Balducci, Lodovico; Komrokji, Rami; Pinilla-Ibarz, Javier","year":2015,"journal":"American journal of hematology, 90(7), 602-7","doi":"10.1002/ajh.24014","pmid":"25802083","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02591","title":"Substance P Weights Striatal Dopamine Transmission Differently within the Striosome-Matrix Axis.","authors":"Brimblecombe, Katherine R; Cragg, Stephanie J","year":2015,"journal":"The Journal of neuroscience : the official journal of the Society for Neuroscience, 35(24), 9017-23","doi":"10.1523/JNEUROSCI.0870-15.2015","pmid":"26085627","tags":["substance-p","dopamine","neuroscience"],"studyType":"Basic Science (Ex Vivo Electrophysiology)","evidenceStrength":"Strong","keyFinding":"Substance P, a neuropeptide concentrated in specific brain compartments called striosomes, has opposite effects on dopamine release depending on exactly where in the striatum you look. In the center of striosomes, substance P boosted dopamine release. At striosome-matrix borders, it suppressed dopamine. In the surrounding matrix, it had no effect.\n\nThis bidirectional modulation creates a \"center-surround contrast\" pattern — substance P sharpens the dopamine signal by enhancing it in one location while suppressing it nearby. The effects were mediated through neurokinin-1 (NK1) receptors. This resolves a long-standing contradiction in the literature, where different studies reported substance P either increasing or decreasing dopamine, depending on where they happened to record.","whyItMatters":"The striatum is the brain's action selection and reward center, and dopamine is its primary currency. Understanding how neuropeptides like substance P fine-tune dopamine signals within the striatum's microarchitecture is essential for understanding disorders like Parkinson's disease, addiction, and compulsive behavior. The discovery that substance P creates a spatial contrast pattern for dopamine suggests it plays a role in sharpening the brain's ability to select between competing actions or rewards.","specificNumbers":"Bidirectional effects · boosted in striosome centers · suppressed at borders · no effect in matrix · mediated via NK1 receptors · resolved conflicting prior findings","methodology":"The researchers measured evoked dopamine release using carbon-fiber microelectrodes in mouse brain slices (ex vivo). After recording dopamine responses in the presence and absence of substance P, they identified the exact anatomical location of each recording site relative to μ-opioid receptor-rich striosomes using immunohistochemistry. This allowed them to correlate substance P's effects with precise compartmental location within the striatum.","limitations":"Ex vivo brain slice recordings capture local effects but may not fully represent the dynamic interactions that occur in the intact brain. The study used mouse tissue, and striatal compartmentalization may differ in humans. Only acute substance P application was tested — chronic or pulsatile neuropeptide release patterns in vivo may produce different effects. The functional consequences of substance P-mediated contrast sharpening for behavior were not tested."},{"rthcId":"RPEP-02592","title":"Which heart failure patients profit from natriuretic peptide guided therapy? A meta-analysis from individual patient data of randomized trials.","authors":"Brunner-La Rocca, Hans-Peter; Eurlings, Luc; Richards, A Mark; Januzzi, James L; Pfisterer, Matthias E; Dahlström, Ulf; Pinto, Yigal M; Karlström, Patric; Erntell, Hans; Berger, Rudolf; Persson, Hans; O'Connor, Christopher M; Moertl, Deddo; Gaggin, Hanna K; Frampton, Christopher M; Nicholls, M Gary; Troughton, Richard W","year":2015,"journal":"European journal of heart failure, 17(12), 1252-61","doi":"10.1002/ejhf.401","pmid":"26419999","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02593","title":"Peripheral neurokinin-1 receptors contribute to kaolin-induced acute monoarthritis in rats.","authors":"Camargo, Livia L; Denadai-Souza, Alexandre; Yshii, Lidia M; Mesquita, Filiphe P N; Soares, Antonio G; Lima, Carla; Schenka, André; Grant, Andrew; Fernandes, Elizabeth; Muscará, Marcelo N; Costa, Soraia K P","year":2015,"journal":"Neuroimmunomodulation, 22(6), 373-84","doi":"10.1159/000381549","pmid":"26088412","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02594","title":"Historical review of thymosin α 1 in infectious diseases.","authors":"Camerini, Roberto; Garaci, Enrico","year":2015,"journal":"Expert opinion on biological therapy, 15 Suppl 1, S117-27","doi":"10.1517/14712598.2015.1033393","pmid":"26098768","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02595","title":"Emerging treatments in Neurogastroenterology: relamorelin: a novel gastrocolokinetic synthetic ghrelin agonist.","authors":"Camilleri, M; Acosta, A","year":2015,"journal":"Neurogastroenterology and motility, 27(3), 324-32","doi":"10.1111/nmo.12490","pmid":"25545036","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02596","title":"Expression of Receptors for Pituitary-Type Growth Hormone-Releasing Hormone (pGHRH-R) in Human Papillary Thyroid Cancer Cells: Effects of GHRH Antagonists on Matrix Metalloproteinase-2.","authors":"Catanuto, Paola; Tashiro, Jun; Rick, Ferenc G; Sanchez, Patricia; Solorzano, Carmen C; Glassberg, Marilyn K; Block, Norman L; Lew, John I; Elliot, Sharon J; Schally, Andrew V","year":2015,"journal":"Hormones & cancer, 6(2-3), 100-6","doi":"10.1007/s12672-015-0217-2","pmid":"25752763","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Both pGHRH-R (pituitary-type GHRH receptor) and its splice variant SV1 were found to be expressed in normal thyroid and papillary thyroid cancer (PTC) cells. Treatment with the GHRH antagonist MIA-602 reduced MMP-2 activity (a marker of tumor invasion capacity) in cancer cells compared to vehicle-treated controls, while normal thyroid cells showed no change in MMP-2 activity.\n\nInterestingly, MIA-602 increased expression of SV1 and pGHRH-R in tumor cells, which may alter signaling kinase sensitivity. However, the treatment did not affect cell proliferation rates in either tumor or normal cells, indicating anti-invasion rather than anti-proliferation activity in this setting.","whyItMatters":"While most papillary thyroid cancers are treatable with surgery and radioactive iodine, aggressive variants can be refractory to conventional therapy. Finding that GHRH antagonist peptides can reduce tumor invasion markers in PTC cells — without affecting normal thyroid tissue — opens a potential new therapeutic avenue for these difficult cases. The selective action on cancer cells is particularly valuable for minimizing treatment side effects.","specificNumbers":"","methodology":"In vitro study using seven normal and papillary thyroid cancer cell preparations. Cells were treated with the GHRH antagonist MIA-602 or vehicle control. Receptor expression (pGHRH-R and SV1) was assessed by Western blot. Cell proliferation was measured by standard assays. MMP-2 activity was quantified as a marker of tumor invasion potential.","limitations":"This was an in vitro study with no animal or clinical data. The lack of anti-proliferative effect may limit standalone therapeutic utility. Only seven cell preparations were tested, and the study did not examine in vivo tumor behavior or metastasis. The mechanism behind the increased receptor expression after antagonist treatment requires further investigation. The clinical relevance of MMP-2 reduction as a surrogate for reduced invasion in actual patients is unproven."},{"rthcId":"RPEP-02597","title":"Involvement of PKA and ERK pathways in ghrelin-induced long-lasting potentiation of excitatory synaptic transmission in the CA1 area of rat hippocampus.","authors":"Cavalier, Mélanie; Crouzin, Nadine; Ben Sedrine, Azza; de Jesus Ferreira, Marie Celeste; Guiramand, Janique; Cohen-Solal, Catherine; Fehrentz, Jean-Alain; Martinez, Jean; Barbanel, Gérard; Vignes, Michel","year":2015,"journal":"The European journal of neuroscience, 42(8), 2568-76","doi":"10.1111/ejn.13013","pmid":"26153524","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02598","title":"Clinical use of pasireotide for Cushing's disease in adults.","authors":"Ceccato, Filippo; Scaroni, Carla; Boscaro, Marco","year":2015,"journal":"Therapeutics and clinical risk management, 11, 425-34","doi":"10.2147/TCRM.S37314","pmid":"25834454","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Pasireotide, a multi-receptor somatostatin analog peptide with high affinity for SST receptor 5, normalized urinary free cortisol levels in up to 28% of patients with Cushing's disease at doses of 600-1,200 μg twice daily after 3 months. Combining pasireotide with cabergoline increased the normalization rate to 50%, and adding ketoconazole achieved biochemical control in most patients. Treatment improved blood pressure, weight, lipid profile, and quality of life. Hyperglycemia is the main side effect, caused by pasireotide's suppression of insulin and GLP-1 secretion.","whyItMatters":"Cushing's disease is a serious condition caused by excess cortisol from a pituitary tumor. Before pasireotide, there was no FDA-approved medical therapy specifically targeting the pituitary tumor cells. Pasireotide represents a milestone as the first peptide drug approved for this indication, working by targeting SST receptor 5 — the predominant somatostatin receptor in corticotroph tumors that remains functional even when cortisol levels are high.","specificNumbers":"600-1,200 μg twice daily · 28% cortisol normalization as monotherapy · 50% normalization with cabergoline combo · most patients controlled with triple therapy · FDA and EMA approved","methodology":"This is a clinical review summarizing the pharmacology, clinical trial results, efficacy data, adverse effects, and practical management considerations for pasireotide use in adult Cushing's disease. It covers both monotherapy and combination therapy approaches.","limitations":"As a review, no new data are presented. The normalization rate of 28% as monotherapy means most patients don't achieve full biochemical control with pasireotide alone. Hyperglycemia is a significant and common side effect that complicates management. Long-term efficacy and safety data beyond the initial clinical trials were limited at the time of publication."},{"rthcId":"RPEP-02599","title":"Sensory Neuropeptides and Endogenous Opioids Expression in Human Dental Pulp with Asymptomatic Inflammation: In Vivo Study.","authors":"Chavarria-Bolaños, Daniel; Flores-Reyes, Hector; Lombana-Sanchez, Nelson; Cerda-Cristerna, Bernardino; Pozos-Guillen, Amaury","year":2015,"journal":"Mediators of inflammation, 2015, 879126","doi":"10.1155/2015/879126","pmid":"26538838","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02600","title":"Androctonus australis hector venom contributes to the interaction between neuropeptides and mast cells in pulmonary hyperresponsiveness.","authors":"Chaïr-Yousfi, Imène; Laraba-Djebari, Fatima; Hammoudi-Triki, Djelila","year":2015,"journal":"International immunopharmacology, 25(1), 19-29","doi":"10.1016/j.intimp.2015.01.008","pmid":"25601496","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02601","title":"α/β-Peptide Foldamers Targeting Intracellular Protein-Protein Interactions with Activity in Living Cells.","authors":"Checco, James W; Lee, Erinna F; Evangelista, Marco; Sleebs, Nerida J; Rogers, Kelly; Pettikiriarachchi, Anne; Kershaw, Nadia J; Eddinger, Geoffrey A; Belair, David G; Wilson, Julia L; Eller, Chelcie H; Raines, Ronald T; Murphy, William L; Smith, Brian J; Gellman, Samuel H; Fairlie, W Douglas","year":2015,"journal":"Journal of the American Chemical Society, 137(35), 11365-75","doi":"10.1021/jacs.5b05896","pmid":"26317395","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Researchers created α/β-peptide foldamers based on a stapled Bim BH3 peptide that could enter cells and block intracellular protein-protein interactions involved in apoptotic signaling — matching the function of the parent stapled α-peptide. Crucially, the α/β-peptide was nearly 100-fold more resistant to proteolytic degradation than the parent stapled α-peptide. This demonstrates that combining backbone modification (α/β substitution) with side chain cross-linking (stapling) produces synergistic benefits for peptide drug design.","whyItMatters":"One of the biggest barriers to using peptides as drugs is that the body breaks them down quickly and they can't get inside cells where many disease-relevant targets exist. This study shows that modifying the peptide backbone with β-amino acids while also using stapling technology solves both problems simultaneously — creating molecules that are dramatically more stable while still functioning inside living cells.","specificNumbers":"","methodology":"The researchers designed α/β-peptide variants of a stapled Bim BH3 α-peptide, incorporating β-amino acid residues into the backbone while maintaining the hydrocarbon cross-link (staple). They tested whether these foldamers could mimic the parent peptide's protein recognition, cell penetration, and ability to block apoptosis-related protein-protein interactions. Proteolytic stability was quantified by comparing degradation rates. Experiments included structural characterization, cell penetration assays, and functional tests in living cells including HCT116 human cancer cells.","limitations":"This is a proof-of-concept study focused on a single protein-protein interaction target (Bim BH3/Bcl-2 family). Cell penetration was shown in certain cell types but may not generalize to all tissues. The study demonstrates the approach in cell-based assays but does not include in vivo animal efficacy data. The 100-fold proteolysis resistance was measured in vitro and may differ in whole-organism pharmacokinetics."},{"rthcId":"RPEP-02602","title":"Genetic modulation of oxytocin sensitivity: a pharmacogenetic approach.","authors":"Chen, F S; Kumsta, R; Dvorak, F; Domes, G; Yim, O S; Ebstein, R P; Heinrichs, M","year":2015,"journal":"Translational psychiatry, 5(10), e664","doi":"10.1038/tp.2015.163","pmid":"26506050","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02603","title":"Therapeutic ultrasound suppresses neuropathic pain and upregulation of substance P and neurokinin-1 receptor in rats after peripheral nerve injury.","authors":"Chen, Yu-Wen; Tzeng, Jann-Inn; Huang, Po-Ching; Hung, Ching-Hsia; Shao, Dong-Zi; Wang, Jhi-Joung","year":2015,"journal":"Ultrasound in medicine & biology, 41(1), 143-50","doi":"10.1016/j.ultrasmedbio.2014.07.022","pmid":"25438854","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02604","title":"Enhancement of neurogenesis and memory by a neurotrophic peptide in mild to moderate traumatic brain injury.","authors":"Chohan, Muhammad Omar; Bragina, Olga; Kazim, Syed Faraz; Statom, Gloria; Baazaoui, Narjes; Bragin, Denis; Iqbal, Khalid; Nemoto, Edwin; Yonas, Howard","year":2015,"journal":"Neurosurgery, 76(2), 201-14; discussion 214-5","doi":"10.1227/NEU.0000000000000577","pmid":"25255260","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Thirty days of Peptide 6 treatment (50 nmol/day) in mice with controlled cortical impact TBI produced multiple beneficial effects:\n\n- 80% increase in newborn neurons in the dentate gyrus (hippocampus), specifically mature neurons rather than uncommitted progenitors\n- Prevention of neuronal loss in the CA1 region and parietal cortex\n- Reversal of TBI-induced dendritic and synaptic density loss\n- Increased activity in tri-synaptic hippocampal circuitry\n- Improved memory recall on behavioral testing\n\nTBI mice also showed increases in Alzheimer-type hyperphosphorylated tau and amyloid-beta, linking TBI pathology to Alzheimer's disease mechanisms. Peptide 6 addressed both the TBI damage and these Alzheimer-associated biomarkers.","whyItMatters":"There are currently no approved drugs that promote brain repair after traumatic brain injury. Peptide 6 is notable because it doesn't just prevent further damage — it actively promotes the growth of new neurons and rebuilds lost synaptic connections, addressing the root problem rather than just managing symptoms. The connection between TBI and Alzheimer's biomarkers makes this doubly relevant, as treating TBI-related damage could potentially reduce Alzheimer's risk.","specificNumbers":"","methodology":"Adult C57BL/6 mice received controlled cortical impact injuries with 1.5 mm of cortical penetration to model mild to moderate TBI. Animals were then treated with either Peptide 6 (50 nmol/day) or saline for 30 days. Researchers quantified dentate gyrus neurogenesis, dendritic and synaptic density, and Alzheimer's disease biomarkers (hyperphosphorylated tau and amyloid-beta) using confocal microscopy and immunohistochemistry. Memory was assessed using behavioral tests.","limitations":"This is a mouse study using a controlled injury model that may not fully replicate the diversity of human TBI. The sample size is not specified in the abstract. The 30-day treatment window started immediately after injury, which may not reflect the delayed treatment scenarios common in clinical practice. Long-term effects beyond 30 days are unknown. The peptide's ability to cross the blood-brain barrier in humans and its pharmacokinetics have not been characterized."},{"rthcId":"RPEP-02605","title":"Potential side effects to GLP-1 agonists: understanding their safety and tolerability.","authors":"Consoli, Agostino; Formoso, Gloria","year":2015,"journal":"Expert opinion on drug safety, 14(2), 207-18","doi":"10.1517/14740338.2015.987122","pmid":"25496749","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02606","title":"Effects of thymosin β4 and its N-terminal fragment Ac-SDKP on TGF-β-treated human lung fibroblasts and in the mouse model of bleomycin-induced lung fibrosis.","authors":"Conte, Enrico; Iemmolo, Maria; Fruciano, Mary; Fagone, Evelina; Gili, Elisa; Genovese, Tiziana; Esposito, Emanuela; Cuzzocrea, Salvatore; Vancheri, Carlo","year":2015,"journal":"Expert opinion on biological therapy, 15 Suppl 1, S211-21","doi":"10.1517/14712598.2015.1026804","pmid":"26098610","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02607","title":"Fel d 1-derived synthetic peptide immuno-regulatory epitopes show a long-term treatment effect in cat allergic subjects.","authors":"Couroux, P; Patel, D; Armstrong, K; Larché, M; Hafner, R P","year":2015,"journal":"Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology, 45(5), 974-981","doi":"10.1111/cea.12488","pmid":"25600085","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02608","title":"Detection and in vitro metabolism of AOD9604.","authors":"Cox, Holly D; Smeal, Stacy J; Hughes, Cole M; Cox, James E; Eichner, Daniel","year":2015,"journal":"Drug testing and analysis, 7(1), 31-8","doi":"10.1002/dta.1715","pmid":"25208511","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02609","title":"Gut microbiota. Antimicrobial peptide resistance mediates resilience of prominent gut commensals during inflammation.","authors":"Cullen, T W; Schofield, W B; Barry, N A; Putnam, E E; Rundell, E A; Trent, M S; Degnan, P H; Booth, C J; Yu, H; Goodman, A L","year":2015,"journal":"Science (New York, N.Y.), 347(6218), 170-5","doi":"10.1126/science.1260580","pmid":"25574022","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02610","title":"A General Synthetic Approach for Designing Epitope Targeted Macrocyclic Peptide Ligands.","authors":"Das, Samir; Nag, Arundhati; Liang, JingXin; Bunck, David N; Umeda, Aiko; Farrow, Blake; Coppock, Matthew B; Sarkes, Deborah A; Finch, Amethist S; Agnew, Heather D; Pitram, Suresh; Lai, Bert; Yu, Mary Beth; Museth, A Katrine; Deyle, Kaycie M; Lepe, Bianca; Rodriguez-Rivera, Frances P; McCarthy, Amy; Alvarez-Villalonga, Belen; Chen, Ann; Heath, John; Stratis-Cullum, Dimitra N; Heath, James R","year":2015,"journal":"Angewandte Chemie (International ed. in English), 54(45), 13219-24","doi":"10.1002/anie.201505243","pmid":"26377818","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Researchers developed a general synthetic strategy for creating high-affinity peptide ligands that target specific epitopes on protein biomarkers. The method uses synthetic epitope fragments with click chemistry-compatible groups that self-select the best binding peptide from a library. The approach successfully generated epitope-targeted linear and macrocyclic peptide ligands against 12 different diagnostic or therapeutic protein targets, producing small molecule alternatives to monoclonal antibodies.","whyItMatters":"Monoclonal antibodies dominate targeted therapeutics and diagnostics but are expensive to produce, temperature-sensitive, and large. This platform produces small peptide ligands with antibody-like targeting precision but in a much smaller, cheaper, and more versatile format — potentially democratizing targeted medicine.","specificNumbers":"12 different protein targets · linear and macrocyclic peptide ligands · Huisgen cycloaddition click chemistry · synthetic epitope (SynEp) approach","methodology":"Synthetic epitope fragments were prepared with a biotin detection tag and an azide or alkyne-presenting amino acid. These SynEps were incubated with libraries of complementary peptides. Peptides that bind in the correct orientation undergo Huisgen cycloaddition (click chemistry), covalently linking to the SynEp. Hit peptides were then validated against full-length target proteins to identify the best binders.","limitations":"The study demonstrates the platform concept across 12 targets but does not provide detailed binding affinity data in the abstract. In vivo performance (pharmacokinetics, stability, efficacy) of the generated peptide ligands was not addressed. The approach requires prior knowledge of the target epitope structure. Translation to clinical applications would require extensive further development."},{"rthcId":"RPEP-02611","title":"Food availability, energetic constraints and reproductive development in a wild seasonally breeding songbird.","authors":"Davies, Scott; Cros, Thomas; Richard, Damien; Meddle, Simone L; Tsutsui, Kazuyoshi; Deviche, Pierre","year":2015,"journal":"Functional ecology, 29(11), 1421-1434","doi":null,"pmid":"27546946","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02612","title":"Bombesin Encapsulated in Long-Circulating pH-Sensitive Liposomes as a Radiotracer for Breast Tumor Identification.","authors":"De Barros, André Luís Branco; Mota, Luciene Das Graças; Coelho, Marina Melo Antunes; Corrêa, Natássia Caroline Resende; De Góes, Alfredo Miranda; Oliveira, Mônica Cristina; Cardoso, Valbert Nascimento","year":2015,"journal":"Journal of biomedical nanotechnology, 11(2), 342-50","doi":null,"pmid":"26349310","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02613","title":"Cullin3-BTB interface: a novel target for stapled peptides.","authors":"de Paola, Ivan; Pirone, Luciano; Palmieri, Maddalena; Balasco, Nicole; Esposito, Luciana; Russo, Luigi; Mazzà, Daniela; Di Marcotullio, Lucia; Di Gaetano, Sonia; Malgieri, Gaetano; Vitagliano, Luigi; Pedone, Emilia; Zaccaro, Laura","year":2015,"journal":"PloS one, 10(4), e0121149","doi":"10.1371/journal.pone.0121149","pmid":"25848797","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Researchers designed stapled peptides based on the Cullin3 protein that successfully mimicked the protein-protein interaction between Cul3 and BTB domain-containing proteins. The stapled peptides adopted the correct helical structure (confirmed by CD and NMR), bound to BTB domains of KCTD11 (tetrameric) and KCTD5 (pentameric) with high affinity (~300-600 nM), and showed increased serum stability compared to unstapled peptides. The binding affinity was comparable to that of the full-length Cul3 protein with its natural BTB partners.","whyItMatters":"Stapled peptides are an emerging class of peptide therapeutics that can disrupt protein-protein interactions — targets traditionally considered 'undruggable' by small molecules. This study demonstrates that stapled peptides can effectively mimic a key protein interaction involved in the ubiquitin degradation system, which controls the breakdown of proteins involved in cancer and other diseases. The approach could lead to new drugs targeting the Cul3-BTB interface.","specificNumbers":"Binding affinity ~300-600 nM · helix 2 residues 49-68 · hydrocarbon cross-linker stapling · increased serum stability · binds tetrameric KCTD11 and pentameric KCTD5","methodology":"The study combined computational modeling with experimental techniques. Stapled peptides were designed from the Cul3 helix 2 region (residues 49-68) and stabilized with hydrocarbon cross-linkers. Their structure was characterized by circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopy. Binding affinity to BTB domains was measured, and serum stability was assessed to evaluate their potential as therapeutic agents.","limitations":"This is an in vitro study with no cellular or in vivo validation of the peptides' biological activity. While binding affinity was demonstrated, the ability of these stapled peptides to actually modulate Cul3-BTB-dependent processes in living cells was not tested. Cell permeability, a common challenge for stapled peptides, was not addressed."},{"rthcId":"RPEP-02614","title":"Review of the Results of WT1 Peptide Vaccination Strategies for Myelodysplastic Syndromes and Acute Myeloid Leukemia from Nine Different Studies.","authors":"Di Stasi, Antonio; Jimenez, Antonio M; Minagawa, Kentaro; Al-Obaidi, Mustafa; Rezvani, Katayoun","year":2015,"journal":"Frontiers in immunology, 6, 36","doi":"10.3389/fimmu.2015.00036","pmid":"25699052","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02615","title":"Triple therapy in type 2 diabetes; a systematic review and network meta-analysis.","authors":"Downes, Martin J; Bettington, Emilie K; Gunton, Jenny E; Turkstra, Erika","year":2015,"journal":"PeerJ, 3, e1461","doi":"10.7717/peerj.1461","pmid":"26664803","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02616","title":"Computational approaches to developing short cyclic peptide modulators of protein-protein interactions.","authors":"Duffy, Fergal J; Devocelle, Marc; Shields, Denis C","year":2015,"journal":"Methods in molecular biology (Clifton, N.J.), 1268, 241-71","doi":"10.1007/978-1-4939-2285-7_11","pmid":"25555728","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The chapter covers several computational strategies for cyclic peptide drug design:\n\n- Virtual screening of cyclic peptide libraries can exploit their constrained shape, which is more predictable than flexible linear peptides\n- Cyclic peptides, while not traditionally 'druglike' by standard rules, may achieve membrane permeability and proteolytic resistance — overcoming the two main barriers to oral peptide delivery\n- Computational approaches include: diverse combinatorial virtual library generation, incorporation of various cyclization strategies and structural modifications, evolutionary algorithms for screening large libraries, machine learning approaches, and bioinformatics-guided library design\n- The constrained conformation of cyclic peptides makes them more amenable to structure-based virtual screening than linear peptides","whyItMatters":"Protein-protein interactions drive many diseases but are considered 'undruggable' by conventional small molecules. Cyclic peptides occupy a sweet spot between small molecules and large biologics — big enough to block protein-protein surfaces but potentially small enough for oral delivery. Computer-aided design could unlock this therapeutic class at scale.","specificNumbers":"","methodology":"This is a methods chapter/review describing computational strategies for designing cyclic peptides, covering virtual screening approaches, library generation methods, cyclization strategies, and advanced techniques like evolutionary algorithms and machine learning.","limitations":"Written in 2015, this chapter predates major advances in deep learning and AI-driven drug design that have since revolutionized the field. Many computational approaches were still in early stages with limited validated successes. The gap between virtual screening hits and actual drug candidates remains large. Oral bioavailability predictions for cyclic peptides remain challenging."},{"rthcId":"RPEP-02617","title":"Oxytocin facilitates the extinction of conditioned fear in humans.","authors":"Eckstein, Monika; Becker, Benjamin; Scheele, Dirk; Scholz, Claudia; Preckel, Katrin; Schlaepfer, Thomas E; Grinevich, Valery; Kendrick, Keith M; Maier, Wolfgang; Hurlemann, René","year":2015,"journal":"Biological psychiatry, 78(3), 194-202","doi":"10.1016/j.biopsych.2014.10.015","pmid":"25542304","tags":["oxytocin","anxiety","fear-extinction"],"studyType":"Randomized Controlled Trial","evidenceStrength":"Strong","keyFinding":"Intranasal oxytocin (24 IU) administered after Pavlovian fear conditioning facilitated fear extinction in healthy men. Using fMRI, researchers showed that oxytocin simultaneously dampened amygdala activity (the brain's fear center) while boosting prefrontal cortex signaling (the region responsible for rational control over fear). This dual action matches exactly what neuroscience models predict would be needed to overcome conditioned fear responses.\n\nSpecifically, in the early phase of extinction, oxytocin increased skin conductance responses and prefrontal cortex activation to conditioned fear stimuli. In the late phase, oxytocin enhanced the decline of fear responses. The amygdala suppression was present in both phases, suggesting a sustained calming effect on the brain's alarm system.","whyItMatters":"Fear extinction — learning that something previously threatening is now safe — is the core mechanism behind exposure therapy for anxiety disorders and PTSD. Many patients struggle with extinction because their amygdala remains overactive while their prefrontal cortex can't provide enough inhibitory control. This study shows that oxytocin addresses both problems simultaneously, making it a potential pharmacological enhancer for exposure therapy. A nasal spray given before therapy sessions could make treatment significantly more effective.","specificNumbers":"n=62 · healthy males · 24 IU intranasal oxytocin · double-blind, placebo-controlled · fMRI + skin conductance · amygdala suppressed + prefrontal cortex enhanced · accelerated extinction in late phase","methodology":"Randomized, double-blind, parallel-group, placebo-controlled fMRI study with 62 healthy male participants. Subjects underwent Pavlovian fear conditioning, then received either intranasal oxytocin (24 IU) or placebo before extinction training. Brain activity was measured via functional magnetic resonance imaging, and skin conductance (electrodermal) responses served as a physiological measure of fear. Both early and late phases of extinction were analyzed separately.","limitations":"Only healthy male participants were studied — results may not generalize to women or to clinical populations with anxiety disorders or PTSD. The Pavlovian fear conditioning paradigm in a lab setting is a simplified model of real-world traumatic fear. The study tested a single dose of oxytocin in a single session; repeated dosing effects are unknown. Intranasal oxytocin's exact pathway to the brain remains debated. The study measured fear extinction but not long-term fear memory or return of fear."},{"rthcId":"RPEP-02618","title":"Dulaglutide: an evidence-based review of its potential in the treatment of type 2 diabetes.","authors":"Edwards, Krystal L; Minze, Molly G","year":2015,"journal":"Core evidence, 10, 11-21","doi":"10.2147/CE.S55944","pmid":"25657615","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Dulaglutide demonstrated efficacy across multiple clinical scenarios: as first-line, second-line, and third-line therapy for type 2 diabetes. Key benefits included reductions in HbA1c, fasting plasma glucose, and postprandial glucose levels, along with weight loss.\n\nAdditional benefits included improved β-cell function and cardiovascular risk factor improvements (lower blood pressure, improved lipid levels). The drug had a low hypoglycemia risk and an adverse effect profile similar to other GLP-1 RAs, primarily transient gastrointestinal symptoms with a potential risk for pancreatitis.","whyItMatters":"The GLP-1 receptor agonist class has become one of the most important treatment options for type 2 diabetes. Dulaglutide's once-weekly dosing offers a practical advantage for patients who prefer less frequent injections, potentially improving adherence to treatment and long-term diabetes management.","specificNumbers":"","methodology":"Evidence-based narrative review examining clinical trial data on dulaglutide's efficacy and safety in type 2 diabetes. The review covers data from the AWARD (Assessment of Weekly Administration of LY2189265 in Diabetes) clinical trial program and other available evidence at the time of publication.","limitations":"This review was published in 2015, relatively early in dulaglutide's clinical use. Long-term safety and efficacy data, including the REWIND cardiovascular outcomes trial results, were not yet available. The review does not compare dulaglutide to newer agents like semaglutide or tirzepatide. Head-to-head comparisons with all other GLP-1 RAs were limited."},{"rthcId":"RPEP-02619","title":"The oncolytic peptide LTX-315 induces cell death and DAMP release by mitochondria distortion in human melanoma cells.","authors":"Eike, Liv-Marie; Yang, Nannan; Rekdal, Øystein; Sveinbjørnsson, Baldur","year":2015,"journal":"Oncotarget, 6(33), 34910-23","doi":"10.18632/oncotarget.5308","pmid":"26472184","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02620","title":"Gut Hormone Suppression Increases Food Intake After Esophagectomy With Gastric Conduit Reconstruction.","authors":"Elliott, Jessie A; Jackson, Sabrina; King, Sinead; McHugh, Ruth; Docherty, Neil G; Reynolds, John V; le Roux, Carel W","year":2015,"journal":"Annals of surgery, 262(5), 824-29; discussion 829-30","doi":"10.1097/SLA.0000000000001465","pmid":"26583672","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02621","title":"A ghrelin receptor (GHS-R1A) antagonist attenuates the rewarding properties of morphine and increases opioid peptide levels in reward areas in mice.","authors":"Engel, Jörgen A; Nylander, Ingrid; Jerlhag, Elisabet","year":2015,"journal":"European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 25(12), 2364-71","doi":"10.1016/j.euroneuro.2015.10.004","pmid":"26508707","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02622","title":"Targeting the Neuropeptide Y System in Stress-related Psychiatric Disorders.","authors":"Enman, Nicole M; Sabban, Esther L; McGonigle, Paul; Van Bockstaele, Elisabeth J","year":2015,"journal":"Neurobiology of stress, 1, 33-43","doi":null,"pmid":"25506604","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02623","title":"Mechanisms of anorexia-cachexia syndrome and rational for treatment with selective ghrelin receptor agonist.","authors":"Esposito, Angela; Criscitiello, Carmen; Gelao, Lucia; Pravettoni, Gabriella; Locatelli, Marzia; Minchella, Ida; Di Leo, Maria; Liuzzi, Rita; Milani, Alessandra; Massaro, Mariangela; Curigliano, Giuseppe","year":2015,"journal":"Cancer treatment reviews, 41(9), 793-7","doi":"10.1016/j.ctrv.2015.09.002","pmid":"26386985","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02624","title":"In vitro models for metabolic studies of small peptide hormones in sport drug testing.","authors":"Esposito, Simone; Deventer, Koen; Geldof, Lore; Van Eenoo, Peter","year":2015,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 21(1), 1-9","doi":"10.1002/psc.2710","pmid":"25469748","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In vitro models using human liver microsomes and S9 fractions successfully generated detectable metabolites for all seven peptide hormones tested: desmopressin, TB-500, GHRP-2, GHRP-6, hexarelin, LHRH, and leuprolide. Both endopeptidase and exopeptidase activity was observed across all models.\n\nComparison between liver and kidney tissue models showed no significant differences in metabolite profiles. Deamidation was not observed in any of the standard models but could be induced using α-chymotrypsin. The authors concluded these in vitro systems are practical tools for forensic and clinical detection of peptide metabolites in biological fluids.","whyItMatters":"Peptide doping agents are notoriously hard to detect because they have very short half-lives in the blood. By mapping how these peptides break down, anti-doping laboratories can search for longer-lasting metabolites instead of the parent drug — dramatically expanding the detection window and making it harder for athletes to cheat undetected.","specificNumbers":"","methodology":"Seven peptide hormones were incubated with human liver microsomes, S9 fractions, and serum samples. The resulting metabolites were identified and compared across models. Liver and kidney tissue models were compared for differences in metabolic profiles. Deamidation was separately evaluated using α-chymotrypsin incubation. This was an in vitro laboratory study with no human subjects.","limitations":"This was purely an in vitro study, so the metabolites observed may not perfectly reflect what happens in a living human body. The study did not establish whether the identified metabolites are actually detectable in urine or blood samples at real-world concentrations after doping use. Ethical constraints prevented direct comparison with human pharmacokinetic data for most of the peptides studied."},{"rthcId":"RPEP-02625","title":"Identification of a novel substance P (SP)-neurokinin-1 receptor (NK-1R) microRNA-221-5p inflammatory network in human colonic epithelial cells.","authors":"Fang, Kai; Sideri, Aristea; Law, Ivy Ka Man; Bakirtzi, Kyriaki; Polytarchou, Christos; Iliopoulos, Dimitrios; Pothoulakis, Charalabos","year":2015,"journal":"Cellular and molecular gastroenterology and hepatology, 1(5), 503-515","doi":null,"pmid":"26645045","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02626","title":"Efficacy of lactoferricin B in controlling ready-to-eat vegetable spoilage caused by Pseudomonas spp.","authors":"Federico, Baruzzi; Pinto, Loris; Quintieri, Laura; Carito, Antonia; Calabrese, Nicola; Caputo, Leonardo","year":2015,"journal":"International journal of food microbiology, 215, 179-86","doi":"10.1016/j.ijfoodmicro.2015.09.017","pmid":"26453993","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02627","title":"Oxytocin and vasopressin effects on the neural response to social cooperation are modulated by sex in humans.","authors":"Feng, Chunliang; Hackett, Patrick D; DeMarco, Ashley C; Chen, Xu; Stair, Sabrina; Haroon, Ebrahim; Ditzen, Beate; Pagnoni, Giuseppe; Rilling, James K","year":2015,"journal":"Brain imaging and behavior, 9(4), 754-64","doi":"10.1007/s11682-014-9333-9","pmid":"25416642","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02628","title":"Bimolecular based heparin and self-assembling hydrogel for tissue engineering applications.","authors":"Fernández-Muiños, Teresa; Recha-Sancho, Lourdes; López-Chicón, Patricia; Castells-Sala, Cristina; Mata, Alvaro; Semino, Carlos E","year":2015,"journal":"Acta biomaterialia, 16, 35-48","doi":"10.1016/j.actbio.2015.01.008","pmid":"25595471","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02629","title":"Fit-for-Purpose Radio Receptor Assay for the Determination of Growth Hormone Secretagogues in Urine.","authors":"Ferro, P; Gutiérrez-Gallego, R; Bosch, J; Farré, M; Segura, J","year":2015,"journal":"Journal of biomolecular screening, 20(10), 1268-76","doi":"10.1177/1087057115594590","pmid":"26160832","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02630","title":"A rationally designed monomeric peptide triagonist corrects obesity and diabetes in rodents.","authors":"Finan, Brian; Yang, Bin; Ottaway, Nickki; Smiley, David L; Ma, Tao; Clemmensen, Christoffer; Chabenne, Joe; Zhang, Lianshan; Habegger, Kirk M; Fischer, Katrin; Campbell, Jonathan E; Sandoval, Darleen; Seeley, Randy J; Bleicher, Konrad; Uhles, Sabine; Riboulet, William; Funk, Jürgen; Hertel, Cornelia; Belli, Sara; Sebokova, Elena; Conde-Knape, Karin; Konkar, Anish; Drucker, Daniel J; Gelfanov, Vasily; Pfluger, Paul T; Müller, Timo D; Perez-Tilve, Diego; DiMarchi, Richard D; Tschöp, Matthias H","year":2015,"journal":"Nature medicine, 21(1), 27-36","doi":"10.1038/nm.3761","pmid":"25485909","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The monomeric peptide triagonist demonstrated supraphysiological potency with equally balanced activity at GLP-1, GIP, and glucagon receptors, without cross-reactivity at other related receptors. It proved superior to the best available dual coagonists and monoagonists at reducing body weight, enhancing glycemic control, and reversing hepatic steatosis in rodent models of obesity. Genetic knockout, pharmacological blockade, and selective chemical knockout experiments confirmed that each receptor's activity contributed to the overall effect: glucagon increased energy expenditure, GLP-1 reduced caloric intake and improved glucose control, and GIP potentiated the incretin effect while buffering against glucagon's diabetogenic potential.","whyItMatters":"This study was foundational for the concept of multi-receptor peptide agonists for metabolic disease — an approach that has since led to drugs like tirzepatide (GLP-1/GIP dual agonist) reaching the market. By demonstrating that triple agonism could outperform any single- or dual-target approach, it established the principle that harmonizing multiple metabolic pathways produces synergistic benefits that no single drug target can match.","specificNumbers":"","methodology":"Researchers rationally designed a monomeric peptide with balanced agonist activity at GLP-1, GIP, and glucagon receptors. They characterized receptor potency and selectivity in cell-based assays, then tested efficacy in multiple rodent models of obesity and diabetes. To prove each receptor contributed, they used genetic knockout mice, pharmacological receptor blockade, and selective chemical knockout approaches. Outcomes included body weight, blood glucose, insulin levels, and liver fat content.","limitations":"All experiments were conducted in rodent models, and metabolic responses in mice and rats do not always translate to humans. The study did not address long-term safety concerns such as thyroid C-cell effects or pancreatitis risk, which have been relevant for GLP-1-class drugs. Rodent models of obesity may not capture the full complexity of human metabolic disease. No human pharmacokinetic or tolerability data were generated."},{"rthcId":"RPEP-02631","title":"Glucagon-like peptide 1 receptor agonists and cardiovascular risk in type 2 diabetes: a clinical perspective.","authors":"Fisher, M","year":2015,"journal":"Diabetes, obesity & metabolism, 17(4), 335-42","doi":"10.1111/dom.12380","pmid":"25155010","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02632","title":"Peptide therapeutics: current status and future directions.","authors":"Fosgerau, Keld; Hoffmann, Torsten","year":2015,"journal":"Drug discovery today, 20(1), 122-8","doi":"10.1016/j.drudis.2014.10.003","pmid":"25450771","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02633","title":"Role of Endogenous Opioid System in Ischemic-Induced Late Preconditioning.","authors":"Fraessdorf, Jan; Hollmann, Markus W; Hanschmann, Iris; Heinen, André; Weber, Nina C; Preckel, Benedikt; Huhn, Ragnar","year":2015,"journal":"PloS one, 10(7), e0134283","doi":"10.1371/journal.pone.0134283","pmid":"26226627","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02634","title":"A hypothesis for a possible synergy between ghrelin and exercise in patients with cachexia: Biochemical and physiological bases.","authors":"Fuoco, Domenico; Kilgour, Robert D; Vigano, Antonio","year":2015,"journal":"Medical hypotheses, 85(6), 927-33","doi":"10.1016/j.mehy.2015.09.008","pmid":"26404870","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02635","title":"Smoke or fire? Acute pancreatitis and the liraglutide trials.","authors":"Gale, Edwin A M","year":2015,"journal":"Diabetes care, 38(6), 948-50","doi":"10.2337/dc15-0346","pmid":"25998284","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02636","title":"The neuropeptide vasoactive intestinal peptide: direct effects on immune cells and involvement in inflammatory and autoimmune diseases.","authors":"Ganea, D; Hooper, K M; Kong, W","year":2015,"journal":"Acta physiologica (Oxford, England), 213(2), 442-52","doi":"10.1111/apha.12427","pmid":"25422088","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"VIP is widely distributed in the central and peripheral nervous system and is also synthesized by immune cells, which express VIP receptors — creating an autocrine/paracrine immunoregulatory loop. VIP contributes to immune privilege in organs like the CNS (central nervous system) by maintaining immune deviation, and controls acute inflammation in peripheral immune organs.\n\nThe review summarizes VIP's broad immunomodulatory effects: it generally suppresses pro-inflammatory responses, shifts T cell differentiation toward regulatory phenotypes, and modulates cytokine production. Both endogenous VIP (naturally produced) and exogenous VIP (administered therapeutically) show potential in inflammatory and autoimmune disorders.","whyItMatters":"The nervous system and immune system are deeply interconnected, but the mechanisms of this communication are still being elucidated. VIP represents one of the clearest examples of a neuropeptide directly controlling immune function. Understanding this could lead to new treatments for autoimmune diseases like multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease — conditions where the immune system attacks the body's own tissues.","specificNumbers":"","methodology":"This is a comprehensive review article synthesizing current literature on VIP biology in the immune system. It covers VIP production by neurons and immune cells, VIP receptor expression and signaling, VIP effects on various immune cell types, and VIP's role in animal models and clinical observations of inflammatory and autoimmune diseases.","limitations":"As a review article, this does not present new experimental data. Much of the evidence comes from animal models, and clinical translation of VIP-based therapies has been limited by VIP's short half-life and multiple biological effects. The review focuses on VIP's immunosuppressive properties, but VIP can have context-dependent effects that complicate therapeutic application. Specificity of VIP receptor targeting for therapeutic benefit without side effects remains a challenge."},{"rthcId":"RPEP-02637","title":"Membrane-induced structure of novel human tachykinin hemokinin-1 (hHK1).","authors":"Ganjiwale, Anjali; Cowsik, Sudha M","year":2015,"journal":"Biopolymers, 103(12), 702-10","doi":"10.1002/bip.22734","pmid":"26297926","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02638","title":"Analogue of Melanotan II (MTII): A Novel Melanotropin with Superpotent Action on Frog Skin.","authors":"Gao, Liqian; Yu, Zhiqiang; Meng, Dan; Zheng, Fang; Ong, Yong S; Miao, Peng; Lee, Su S; Wen, Longping","year":2015,"journal":"Protein and peptide letters, 22(8), 762-6","doi":null,"pmid":"26095376","tags":["melanocortin-peptides","melanotan"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"A modified version of the melanotropin peptide Melanotan II (MTII) — called F Peptide — showed superpotent and ultra-prolonged pigmentation activity in frogs. The modification involved replacing arginine at position 8 with lysine and adding a glycine at position 10, expanding the cyclic ring. In vivo testing showed the F Peptide matched MTII's melanotropic potency but lasted significantly longer, making it one of the most sustained-action melanocortin agonists reported.","whyItMatters":"Melanotan II is one of the most studied melanocortin receptor agonists, with effects on pigmentation, sexual function, and appetite. Creating analogs with longer-lasting activity could improve research tools and potentially lead to therapeutics that require less frequent dosing. Understanding which structural modifications enhance duration of action guides the broader field of melanocortin peptide drug design.","specificNumbers":"","methodology":"Researchers synthesized the F Peptide analog by modifying MTII's core cyclic structure — replacing Arg-8 with Lys and adding Gly-10. They tested it in frogs by measuring pigment granule movement within chromatophores (pigment cells), comparing the onset, intensity, and duration of skin color change to standard MTII.","limitations":"This study was conducted exclusively in frogs, whose melanocortin system differs from mammals. No mammalian receptor binding data, selectivity profiles, or safety data were reported. The frog chromatophore assay measures pigmentation only and doesn't address other melanocortin receptor-mediated effects (appetite, sexual function). Sample sizes and statistical analyses were not detailed in the abstract."},{"rthcId":"RPEP-02639","title":"Thymosin Beta-4 Induces Mouse Hair Growth.","authors":"Gao, Xiaoyu; Liang, Hao; Hou, Fang; Zhang, Zhipeng; Nuo, Mingtu; Guo, Xudong; Liu, Dongjun","year":2015,"journal":"PloS one, 10(6), e0130040","doi":"10.1371/journal.pone.0130040","pmid":"26083021","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02640","title":"Historical review on thymosin α1 in oncology: preclinical and clinical experiences.","authors":"Garaci, Enrico; Pica, Francesca; Matteucci, Claudia; Gaziano, Roberta; D'Agostini, Cartesio; Miele, Martino Tony; Camerini, Roberto; Palamara, Anna Teresa; Favalli, Cartesio; Mastino, Antonio; Serafino, Annalucia; Sinibaldi Vallebona, Paola","year":2015,"journal":"Expert opinion on biological therapy, 15 Suppl 1, S31-9","doi":"10.1517/14712598.2015.1017466","pmid":"26096345","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Thymosin alpha-1 (Tα1) demonstrates significant potential as an immunotherapeutic agent in cancer treatment when combined with chemotherapy. Preclinical studies in murine models established the efficacy and safety of combining Tα1 with chemotherapy and cytokines, and these findings were confirmed in controlled clinical trials for metastatic melanoma and lung cancer. The peptide's dual action on both immune effector cells and tumor cells directly is considered critical for the success of chemo-immunotherapy protocols.","whyItMatters":"Cancer treatment often suppresses the immune system, which paradoxically can allow tumors to progress. Thymosin alpha-1 addresses this by boosting immune function while also directly affecting tumor cells. This review makes a strong case for incorporating Tα1 into standard chemotherapy protocols, a concept that despite clinical evidence still hasn't been fully adopted in routine oncology practice.","specificNumbers":"Review article · covers preclinical murine models + controlled clinical trials · melanoma and lung cancer focus · combination chemo-immunotherapy protocol","methodology":"This is a historical review paper that synthesizes preclinical data from murine tumor models and results from controlled clinical trials. It traces the development of thymosin alpha-1 from laboratory studies through clinical application, examining the evidence for combining it with chemotherapy and cytokines in cancer treatment.","limitations":"As a review paper, this does not present new primary data. The clinical trials discussed focused primarily on melanoma and lung cancer, so applicability to other cancer types is less established. The authors have been long-term advocates for Tα1 research, which may introduce some selection bias in the literature reviewed."},{"rthcId":"RPEP-02641","title":"Biological and Pharmacological Aspects of the NK1-Receptor.","authors":"Garcia-Recio, Susana; Gascón, Pedro","year":2015,"journal":"BioMed research international, 2015, 495704","doi":"10.1155/2015/495704","pmid":"26421291","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02642","title":"The Transmodulation of HER2 and EGFR by Substance P in Breast Cancer Cells Requires c-Src and Metalloproteinase Activation.","authors":"Garcia-Recio, Susana; Pastor-Arroyo, Eva M; Marín-Aguilera, Mercedes; Almendro, Vanessa; Gascón, Pedro","year":2015,"journal":"PloS one, 10(6), e0129661","doi":"10.1371/journal.pone.0129661","pmid":"26114632","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The neuropeptide Substance P activates the cancer-driving receptors HER2 and EGFR in breast cancer cells through two pathways requiring c-Src kinase and metalloproteinases (MMPs). Inhibiting c-Src alone prevented Substance P-induced HER2 activation, while MMP inhibition reduced phosphorylation of both HER2 and EGFR. Dual inhibition of both c-Src and MMPs nearly abolished HER2 and EGFR activation and also reduced breast cancer cell viability and migration. These findings reveal that Substance P's tumor-promoting effects in breast cancer depend on both ligand-independent (c-Src) and ligand-dependent (MMP) signaling pathways.","whyItMatters":"HER2 and EGFR are major targets in breast cancer treatment, but drug resistance remains a significant clinical challenge. This study reveals that the neuropeptide Substance P can activate these receptors through an alternative route — the NK-1 receptor — bypassing the pathways that current targeted therapies block. Understanding this cross-talk mechanism could inform new combination treatment strategies to overcome drug resistance in HER2+ and EGFR+ breast cancers.","specificNumbers":"4 breast cancer cell lines tested · Dual c-Src + MMP inhibition nearly abolished HER2/EGFR activation · NK-1R overexpression modulated c-Src activation","methodology":"In vitro cell biology study using four breast cancer cell lines (MDA-MB-231, SK-BR-3, BT-474, MDA-MB-468). NK-1 receptor was overexpressed in one line and chemically inhibited in others. The roles of c-Src and metalloproteinases in Substance P-mediated HER2/EGFR activation were tested using specific inhibitors (c-Src inhibitor and MMP inhibitor 1,10-phenanthroline monohydrate). Cell viability and migration were assessed under single and dual inhibition conditions.","limitations":"This is an in vitro study using cultured breast cancer cell lines, which may not fully represent the complexity of tumors in patients. The interactions between Substance P, the tumor microenvironment, and the immune system were not captured. No animal models or patient samples were used to validate the findings in a more physiological context."},{"rthcId":"RPEP-02643","title":"Gabaergic control of anxiety-like behavior, but not food intake, induced by ghrelin in the intermediate medial mesopallium of the neonatal chick.","authors":"Gastón, M S; Schiöth, H B; De Barioglio, S R; Salvatierra, N A","year":2015,"journal":"Hormones and behavior, 67, 66-72","doi":"10.1016/j.yhbeh.2014.11.015","pmid":"25499794","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02644","title":"Neurological heterotopic ossification following spinal cord injury is triggered by macrophage-mediated inflammation in muscle.","authors":"Genêt, François; Kulina, Irina; Vaquette, Cedryck; Torossian, Frédéric; Millard, Susan; Pettit, Allison R; Sims, Natalie A; Anginot, Adrienne; Guerton, Bernadette; Winkler, Ingrid G; Barbier, Valérie; Lataillade, Jean-Jacques; Le Bousse-Kerdilès, Marie-Caroline; Hutmacher, Dietmar W; Levesque, Jean-Pierre","year":2015,"journal":"The Journal of pathology, 236(2), 229-40","doi":"10.1002/path.4519","pmid":"25712044","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02645","title":"Ghrelin increases memory consolidation through hippocampal mechanisms dependent on glutamate release and NR2B-subunits of the NMDA receptor.","authors":"Ghersi, Marisa S; Gabach, L A; Buteler, F; Vilcaes, A A; Schiöth, H B; Perez, M F; de Barioglio, S R","year":2015,"journal":"Psychopharmacology, 232(10), 1843-57","doi":"10.1007/s00213-014-3817-6","pmid":"25466701","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02646","title":"Dual effect of Thymosin α 1 on human monocyte-derived dendritic cell in vitro stimulated with viral and bacterial toll-like receptor agonists.","authors":"Giacomini, Elena; Severa, Martina; Cruciani, Melania; Etna, Marilena Paola; Rizzo, Fabiana; Pardini, Manuela; Scagnolari, Carolina; Garaci, Enrico; Coccia, Eliana Marina","year":2015,"journal":"Expert opinion on biological therapy, 15 Suppl 1, S59-70","doi":"10.1517/14712598.2015.1019460","pmid":"26096650","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Thymosin α1 enhanced HLA-I and HLA-II surface expression and secretion of IL-6, TNF-α, and IL-8 when dendritic cells were stimulated with viral TLR3 and TLR7/8 agonists. In H1N1 influenza A-infected DCs, Thymosin α1 increased maturation markers and type I and III interferon production.\n\nIn contrast, following bacterial TLR2 and TLR4 stimulation, as well as upon Bacillus Calmette-Guerin infection, Thymosin α1 drastically lowered DC maturation markers and cytokine production. This reveals a context-dependent dual effect: pro-inflammatory in viral settings and anti-inflammatory in bacterial settings.","whyItMatters":"Most immune-modulating drugs are either stimulatory or suppressive. Thymosin α1's ability to distinguish between viral and bacterial threats and respond appropriately is remarkable. This dual action could make it uniquely suited as a vaccine adjuvant that boosts antiviral immunity while preventing the excessive inflammation that can accompany bacterial infections — a more nuanced approach to immune modulation.","specificNumbers":"","methodology":"Human monocyte-derived dendritic cells were cultured in vitro with or without Thymosin α1 and then exposed to various toll-like receptor agonists: TLR3 (viral), TLR7/8 (viral), TLR2 (bacterial), and TLR4 (bacterial). DCs were also infected with pandemic H1N1 influenza A virus or Bacillus Calmette-Guerin bacteria. DC maturation markers, HLA expression, and cytokine production (IL-6, TNF-α, IL-8, interferons) were measured.","limitations":"This is an in vitro study using human monocyte-derived dendritic cells, which may not fully represent the complexity of immune responses in vivo. The mechanisms underlying the dual effect were not fully elucidated. The TLR agonists used are simplified models of viral and bacterial infection. Dose-response relationships for Thymosin α1 were not detailed in the abstract. Clinical relevance of these in vitro findings needs to be confirmed in human studies."},{"rthcId":"RPEP-02647","title":"The impact of diabetes and diabetes medications on bone health.","authors":"Gilbert, Matthew P; Pratley, Richard E","year":2015,"journal":"Endocrine reviews, 36(2), 194-213","doi":"10.1210/er.2012-1042","pmid":"25738213","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02648","title":"Incretin-based therapies and acute pancreatitis risk: a systematic review and meta-analysis of observational studies.","authors":"Giorda, Carlo B; Sacerdote, Carlotta; Nada, Elisa; Marafetti, Lisa; Baldi, Ileana; Gnavi, Roberto","year":2015,"journal":"Endocrine, 48(2), 461-71","doi":"10.1007/s12020-014-0386-8","pmid":"25146552","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02649","title":"Efficacy and Safety of Once-Weekly Dulaglutide Versus Insulin Glargine in Patients With Type 2 Diabetes on Metformin and Glimepiride (AWARD-2).","authors":"Giorgino, Francesco; Benroubi, Marian; Sun, Jui-Hung; Zimmermann, Alan G; Pechtner, Valeria","year":2015,"journal":"Diabetes care, 38(12), 2241-9","doi":"10.2337/dc14-1625","pmid":"26089386","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02650","title":"Sensory nerves contribute to cutaneous vasodilator response to cathodal stimulation in healthy rats.","authors":"Gohin, Stéphanie; Decorps, Johanna; Sigaudo-Roussel, Dominique; Fromy, Bérengère","year":2015,"journal":"Microvascular research, 101, 103-10","doi":"10.1016/j.mvr.2015.06.010","pmid":"26205659","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02651","title":"Single housing during early adolescence causes time-, area- and peptide-specific alterations in endogenous opioids of rat brain.","authors":"Granholm, L; Roman, E; Nylander, I","year":2015,"journal":"British journal of pharmacology, 172(2), 606-14","doi":"10.1111/bph.12753","pmid":"24821004","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02652","title":"The effects of a course of intranasal oxytocin on social behaviors in youth diagnosed with autism spectrum disorders: a randomized controlled trial.","authors":"Guastella, Adam J; Gray, Kylie M; Rinehart, Nicole J; Alvares, Gail A; Tonge, Bruce J; Hickie, Ian B; Keating, Caroline M; Cacciotti-Saija, Cristina; Einfeld, Stewart L","year":2015,"journal":"Journal of child psychology and psychiatry, and allied disciplines, 56(4), 444-52","doi":"10.1111/jcpp.12305","pmid":"25087908","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02653","title":"Fractionation and identification of Alaska pollock skin collagen-derived mineral chelating peptides.","authors":"Guo, Lidong; Harnedy, Pádraigín A; O'Keeffe, Martina B; Zhang, Li; Li, Bafang; Hou, Hu; FitzGerald, Richard J","year":2015,"journal":"Food chemistry, 173, 536-42","doi":"10.1016/j.foodchem.2014.10.055","pmid":"25466056","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02654","title":"In vitro assessment of the multifunctional bioactive potential of Alaska pollock skin collagen following simulated gastrointestinal digestion.","authors":"Guo, Lidong; Harnedy, Pádraigín A; Zhang, Li; Li, Bafang; Zhang, Zhaohui; Hou, Hu; Zhao, Xue; FitzGerald, Richard J","year":2015,"journal":"Journal of the science of food and agriculture, 95(7), 1514-20","doi":"10.1002/jsfa.6854","pmid":"25082083","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02655","title":"A novel, long-acting glucagon-like peptide receptor-agonist: dulaglutide.","authors":"Gurung, Tara; Shyangdan, Deepson S; O'Hare, Joseph Paul; Waugh, Norman","year":2015,"journal":"Diabetes, metabolic syndrome and obesity : targets and therapy, 8, 363-86","doi":"10.2147/DMSO.S34418","pmid":"26316788","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across four AWARD randomized controlled trials with follow-up ranging from 26 to 104 weeks, dulaglutide demonstrated superior or noninferior glycemic control compared to all tested comparators:\n\n• vs exenatide 10 µg twice daily: HbA1c reduction of -1.5% (1.5 mg) and -1.3% (0.75 mg) vs -0.99%\n• vs sitagliptin 100 mg daily: -1.22% (1.5 mg) and -1.01% (0.75 mg) vs -0.6%\n• vs insulin glargine: -1.08% (1.5 mg) vs -0.63% (significant); -0.76% (0.75 mg) vs -0.63% (not significant)\n• vs liraglutide 1.8 mg daily: dulaglutide 1.5 mg was noninferior\n\nMore dulaglutide patients achieved HbA1c targets of <7% and ≤6.5%. Weight reduction was greater with dulaglutide than sitagliptin and exenatide. Hypoglycemia was infrequent across all dulaglutide groups.","whyItMatters":"GLP-1 receptor agonists have transformed type 2 diabetes treatment, and dulaglutide's once-weekly dosing offers a major convenience advantage. This systematic review provided early comprehensive evidence that dulaglutide was not just convenient but also more effective than several established treatments, supporting its adoption as a frontline option for patients struggling with blood sugar control.","specificNumbers":"","methodology":"Systematic review searching MEDLINE, MEDLINE In-Process, EMBASE, and conference abstracts from 2005 to January 2015. FDA and EMA websites and company data were also searched. Four manufacturer-funded randomized controlled trials from the AWARD program were included, comparing dulaglutide (0.75 mg and 1.5 mg once weekly) against exenatide, insulin glargine, sitagliptin, liraglutide, and placebo. The primary outcome was change in HbA1c.","limitations":"All four included trials were manufacturer-funded, introducing potential bias. The review notes that long-term safety data were still needed at the time of publication. Only dual and triple therapy combinations were assessed. The comparator doses and regimens varied across trials, making direct cross-trial comparisons imprecise. The search ended in early 2015, so subsequent AWARD trials and real-world evidence are not included."},{"rthcId":"RPEP-02656","title":"Pharmacokinetics and pharmacodynamics of the glucagon-like peptide-1 analog liraglutide in healthy cats.","authors":"Hall, M J; Adin, C A; Borin-Crivellenti, S; Rudinsky, A J; Rajala-Schultz, P; Lakritz, J; Gilor, C","year":2015,"journal":"Domestic animal endocrinology, 51, 114-21","doi":"10.1016/j.domaniend.2014.12.001","pmid":"25625650","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02657","title":"Mitochondrion-Targeted Peptide SS-31 Inhibited Oxidized Low-Density Lipoproteins-Induced Foam Cell Formation through both ROS Scavenging and Inhibition of Cholesterol Influx in RAW264.7 Cells.","authors":"Hao, Shuangying; Ji, Jiajie; Zhao, Hongting; Shang, Longcheng; Wu, Jing; Li, Huihui; Qiao, Tong; Li, Kuanyu","year":2015,"journal":"Molecules (Basel, Switzerland), 20(12), 21287-97","doi":"10.3390/molecules201219764","pmid":"26633327","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02658","title":"One-year intranasal application of growth hormone releasing peptide-2 improves body weight and hypoglycemia in a severely emaciated anorexia nervosa patient.","authors":"Haruta, Izumi; Fuku, Yuki; Kinoshita, Kazuhisa; Yoneda, Koichi; Morinaga, Akinori; Amitani, Marie; Amitani, Haruka; Asakawa, Akihiro; Sugawara, Hideki; Takeda, Yasuo; Bowers, Cyril Y; Inui, Akio","year":2015,"journal":"Journal of cachexia, sarcopenia and muscle, 6(3), 237-41","doi":"10.1002/jcsm.12028","pmid":"26401470","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02659","title":"Amylin: Pharmacology, Physiology, and Clinical Potential.","authors":"Hay, Debbie L; Chen, Steve; Lutz, Thomas A; Parkes, David G; Roth, Jonathan D","year":2015,"journal":"Pharmacological reviews, 67(3), 564-600","doi":"10.1124/pr.115.010629","pmid":"26071095","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Amylin is a 37-amino acid peptide hormone co-secreted with insulin from pancreatic beta cells. Its receptors are unique multisubunit G protein-coupled receptors formed by combining a core receptor protein with receptor activity-modifying proteins (RAMPs), creating multiple receptor subtypes.\n\nKey roles and findings from 25 years of research:\n- Primary function: glucoregulation — amylin helps control blood sugar alongside insulin\n- Appetite regulation: acts in circumventricular organs of the brain to reduce food intake\n- Metabolic interactions: functionally interacts with cholecystokinin, leptin, and estradiol\n- Additional effects: cardiovascular and bone actions have been reported\n- Clinical use: pramlintide (amylin analog) is FDA-approved for type 1 and type 2 diabetes\n- Obesity potential: clinical studies show amylin agonists promote weight loss, especially in combination therapy","whyItMatters":"Amylin represents a critical piece of the metabolic puzzle that is often overshadowed by insulin. Understanding amylin has led to pramlintide (an FDA-approved diabetes treatment) and is now driving research into combination therapies for obesity. The recent success of amylin analog cagrilintide in combination with semaglutide (CagriSema) has renewed intense interest in this pathway.","specificNumbers":"","methodology":"This is a comprehensive narrative review published in Pharmacological Reviews, covering the full scope of amylin research from its discovery as a hormone through 2015. It synthesizes findings from rodent studies, human clinical trials, and basic receptor pharmacology research.","limitations":"As a narrative review, it synthesizes existing research without generating new data. Published in 2015, it predates the recent surge in amylin analog development for obesity (particularly cagrilintide). Some of the clinical potential discussed was speculative at the time and has since been confirmed or refined by newer studies."},{"rthcId":"RPEP-02660","title":"Morphology and neurochemistry of rabbit iris innervation.","authors":"He, Jiucheng; Bazan, Haydee E P","year":2015,"journal":"Experimental eye research, 135, 182-91","doi":"10.1016/j.exer.2015.03.005","pmid":"25752697","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"This is the first complete two-dimensional map of iris nerve architecture. CGRP-positive nerve fibers constituted approximately 61% of anterior and 69% of posterior iris nerve content, while Substance P-positive fibers made up about 30.5% (anterior) and 20% (posterior). All SP-positive neurons in the trigeminal ganglia were also CGRP-positive, indicating co-expression. The iris has a complex nerve architecture with 4–5 stromal nerve rings, a superficial anterior network, and radial posterior nerve bundles running along the dilator muscle. The pupillary margin had the densest innervation. Non-neuronal SP-positive cells were also found in the anterior stroma.","whyItMatters":"The iris is richly innervated by neuropeptide-containing nerve fibers, and these peptides — CGRP and Substance P — are known mediators of inflammation and pain. Their high expression in the iris suggests they play important roles in eye conditions like uveitis, glaucoma, cataracts, and chronic ocular pain. Understanding this anatomy could guide the development of peptide-targeted therapies for these diseases.","specificNumbers":"CGRP: ~61% anterior, ~69% posterior · SP: ~30.5% anterior, ~20% posterior · 4–5 stromal nerve rings · pupillary margin densest · all SP neurons co-express CGRP","methodology":"Whole-mount immunohistochemistry of rabbit irises using antibodies against βIII-tubulin (total nerve marker), CGRP, and Substance P. Time-lapse imaging built two-dimensional maps of the complete iris nerve architecture. Computer-assisted quantitative analysis measured relative nerve fiber densities for each peptide. Trigeminal ganglia were also examined for neuropeptide expression.","limitations":"Rabbit iris anatomy may differ from human iris innervation in some respects. The study provided relative peptide proportions but not absolute fiber counts. Functional roles of CGRP and SP in the iris were inferred from their known roles elsewhere but not directly tested in this study. Only two neuropeptides were examined; other peptides may also be present."},{"rthcId":"RPEP-02661","title":"An enhanced functional interrogation/manipulation of intracellular signaling pathways with the peptide 'stapling' technology.","authors":"He, Y; Chen, D; Zheng, W","year":2015,"journal":"Oncogene, 34(46), 5685-98","doi":"10.1038/onc.2015.37","pmid":"25798838","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02662","title":"Cell-permeable cyclic peptides from synthetic libraries inspired by natural products.","authors":"Hewitt, William M; Leung, Siegfried S F; Pye, Cameron R; Ponkey, Alexandra R; Bednarek, Maria; Jacobson, Matthew P; Lokey, R Scott","year":2015,"journal":"Journal of the American Chemical Society, 137(2), 715-21","doi":"10.1021/ja508766b","pmid":"25517352","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Using a combinatorial library approach with synthesis and deconvolution, researchers identified multiple geometrically diverse cyclic peptide scaffolds with good to excellent passive cell permeability. Experimental and computational analysis of structure-permeability relationships revealed specific structural and conformational factors governing passive membrane diffusion among cyclic peptide diastereomers.\n\nCritically, single-point side-chain diversifications of one scaffold demonstrated that permeability could be maintained while varying the functional groups — meaning these scaffolds can be adapted for bioactivity screening against different targets without losing cell permeability. The results show that the chemical space of cell-permeable cyclic peptides extends far beyond known natural products.","whyItMatters":"Many high-value drug targets — especially protein-protein interactions involved in cancer, autoimmune diseases, and infections — are considered 'undruggable' because they require molecules too large for traditional drugs but too complex for standard peptides. Cell-permeable cyclic peptides bridge this gap. This methodology enables rapid discovery of scaffolds that can enter cells, greatly expanding the chemical toolkit available for drug design against these challenging targets.","specificNumbers":"","methodology":"Researchers synthesized a combinatorial library of cyclic peptides inspired by natural product structures and screened them for membrane permeability. Membrane-permeable scaffolds were identified through library deconvolution. Structure-permeability relationships were investigated using a combination of experimental permeability assays (including Caco-2 cell assays) and computational modeling. Side-chain diversification was tested to assess scaffold adaptability for building target-specific libraries.","limitations":"The study focused on identifying permeable scaffolds rather than demonstrating bioactivity against specific disease targets. Permeability was measured primarily in cell-based assays (Caco-2), which may not fully predict in vivo behavior. Oral bioavailability and metabolic stability were not assessed. The approach identifies passive permeability but does not address active transport or efflux mechanisms that affect drug delivery in vivo."},{"rthcId":"RPEP-02663","title":"Role of Amylin in Type 1 and Type 2 Diabetes.","authors":"Hieronymus, Laura; Griffin, Stacy","year":2015,"journal":"The Diabetes educator, 41(1 Suppl), 47S-56S","doi":"10.1177/0145721715607642","pmid":"26424675","tags":["amylin","pramlintide"],"studyType":"review","evidenceStrength":"reference","keyFinding":"Amylin plays three key roles in glucose homeostasis: suppressing post-meal glucagon release, delaying gastric emptying, and activating satiety centers in the brain to reduce caloric intake. Type 1 diabetes patients have absent amylin response to meals, while insulin-requiring type 2 patients have diminished response proportional to beta-cell impairment.\n\nPramlintide, the synthetic amylin analog, demonstrated significant HbA1c reductions in both type 1 and type 2 diabetes when added to insulin therapy, with favorable effects on body weight — an important advantage since insulin itself tends to promote weight gain. Key risks include increased hypoglycemia when combined with insulin and gastrointestinal side effects including nausea.","whyItMatters":"Diabetes treatment has traditionally focused almost entirely on insulin, but this review highlights that diabetes involves multiple hormonal deficiencies — including amylin. Replacing amylin alongside insulin provides a more complete hormonal restoration that improves glucose control and addresses the weight gain problem that plagues insulin therapy. Understanding amylin's role has also influenced the development of newer combination approaches like cagrilintide (an amylin analog) paired with semaglutide.","specificNumbers":"Amylin absent in T1D; diminished in insulin-requiring T2D; pramlintide reduces A1C and body weight as adjunct to insulin","methodology":"Narrative review of amylin physiology, pathophysiology in diabetes, and clinical evidence for pramlintide use in type 1 and type 2 diabetes. Published in a diabetes education journal.","limitations":"Narrative review, not systematic; no specific effect sizes reported; predates newer amylin analog developments; aimed at educators rather than researchers."},{"rthcId":"RPEP-02664","title":"Pathophysiological mechanisms involved in non-alcoholic steatohepatitis and novel potential therapeutic targets.","authors":"Higuera-de la Tijera, Fátima; Servín-Caamaño, Alfredo I","year":2015,"journal":"World journal of hepatology, 7(10), 1297-301","doi":"10.4254/wjh.v7.i10.1297","pmid":"26052375","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02665","title":"Appetite-related peptides in childhood and adolescence: role of ghrelin, PYY, and GLP-1.","authors":"Horner, Katy; Lee, SoJung","year":2015,"journal":"Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme, 40(11), 1089-99","doi":"10.1139/apnm-2015-0050","pmid":"26466085","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02666","title":"Evaluation of iron-binding activity of collagen peptides prepared from the scales of four cultivated fishes in Taiwan.","authors":"Huang, Chun-Yung; Wu, Chien-Hui; Yang, Jing-Iong; Li, Ying-Han; Kuo, Jen-Min","year":2015,"journal":"Journal of food and drug analysis, 23(4), 671-678","doi":"10.1016/j.jfda.2014.06.009","pmid":"28911483","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02667","title":"Body protective compound-157 enhances alkali-burn wound healing in vivo and promotes proliferation, migration, and angiogenesis in vitro.","authors":"Huang, Tonglie; Zhang, Kuo; Sun, Lijuan; Xue, Xiaochang; Zhang, Cun; Shu, Zhen; Mu, Nan; Gu, Jintao; Zhang, Wangqian; Wang, Yukun; Zhang, Yingqi; Zhang, Wei","year":2015,"journal":"Drug design, development and therapy, 9, 2485-99","doi":"10.2147/DDDT.S82030","pmid":"25995620","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Topical BPC-157 accelerated wound closure in an alkali burn rat model compared to controls. By day 18 post-injury, treated wounds showed superior granulation tissue formation, reepithelialization, dermal remodeling, and collagen deposition on histological examination.\n\nThe mechanism was traced to angiogenesis (new blood vessel formation): BPC-157 increased VEGF expression in wounded skin, promoted proliferation and migration of human umbilical vein endothelial cells (HUVECs), and accelerated vascular tube formation in vitro. The ERK1/2 signaling pathway and its downstream targets (c-Fos, c-Jun, Egr-1) were identified as key mediators of these effects.","whyItMatters":"Chemical burns are common industrial and household injuries with limited treatment options. BPC-157's ability to promote both tissue regeneration and new blood vessel formation through a defined signaling pathway provides mechanistic support for its wound healing potential. Understanding the ERK1/2 mechanism also opens avenues for optimizing peptide-based wound therapies.","specificNumbers":"","methodology":"In vivo: Alkali burns were created on the skin of Sprague-Dawley rats, and BPC-157 was applied topically. Wound closure was monitored, and skin sections were examined histologically with H&E and Masson staining at day 18. In vitro: Human umbilical vein endothelial cells (HUVECs) were treated with BPC-157 and assessed for proliferation (MTT assay, cell cycle analysis), migration (Transwell and wound healing assays), VEGF expression, tube formation, and ERK1/2 pathway activation.","limitations":"This is an animal study in rats — results may not translate directly to human chemical burns. The study doesn't report specific BPC-157 doses or concentrations used topically. Only one time point (day 18) was examined histologically, so the full healing trajectory is unclear. No human clinical trial data exists for BPC-157 in burn treatment."},{"rthcId":"RPEP-02668","title":"Feeding-induced oleoylethanolamide mobilization is disrupted in the gut of diet-induced obese rodents.","authors":"Igarashi, Miki; DiPatrizio, Nicholas V; Narayanaswami, Vidya; Piomelli, Daniele","year":2015,"journal":"Biochimica et biophysica acta, 1851(9), 1218-26","doi":"10.1016/j.bbalip.2015.05.006","pmid":"26024927","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02669","title":"New perspectives on exploitation of incretin peptides for the treatment of diabetes and related disorders.","authors":"Irwin, Nigel; Flatt, Peter R","year":2015,"journal":"World journal of diabetes, 6(15), 1285-95","doi":"10.4239/wjd.v6.i15.1285","pmid":"26557956","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02670","title":"Artificial human Met agonists based on macrocycle scaffolds.","authors":"Ito, Kenichiro; Sakai, Katsuya; Suzuki, Yoshinori; Ozawa, Naoya; Hatta, Tomohisa; Natsume, Tohru; Matsumoto, Kunio; Suga, Hiroaki","year":2015,"journal":"Nature communications, 6, 6373","doi":"10.1038/ncomms7373","pmid":"25758345","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02671","title":"The regulation of circulating ghrelin - with recent updates from cell-based assays.","authors":"Iwakura, Hiroshi; Kangawa, Kenji; Nakao, Kazuwa","year":2015,"journal":"Endocrine journal, 62(2), 107-22","doi":"10.1507/endocrj.EJ14-0419","pmid":"25273611","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02672","title":"Sphingosine kinase 1 activation enhances epidermal innate immunity through sphingosine-1-phosphate stimulation of cathelicidin production.","authors":"Jeong, Se Kyoo; Kim, Young Il; Shin, Kyong-Oh; Kim, Bong-Woo; Lee, Sin Hee; Jeon, Jeong Eun; Kim, Hyun Jong; Lee, Yong-Moon; Mauro, Theodora M; Elias, Peter M; Uchida, Yoshikazu; Park, Kyungho","year":2015,"journal":"Journal of dermatological science, 79(3), 229-34","doi":"10.1016/j.jdermsci.2015.06.007","pmid":"26113114","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02673","title":"Thymosin α1 plus routine treatment inhibit inflammatory reaction and improve the quality of life in AECOPD patients.","authors":"Jia, Zhiyang; Feng, Zihui; Tian, Rui; Wang, Qian; Wang, Linyu","year":2015,"journal":"Immunopharmacology and immunotoxicology, 37(4), 388-92","doi":null,"pmid":"26250523","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02674","title":"Ghrelin inhibition of ethanol-induced gastric epithelial cell apoptosis is mediated by miR-21.","authors":"Jiang, Miao; Gao, Peng-Fei; Li, Huan-Qing; Tian, Pei-Ying; Fan, Xiao-Ming","year":2015,"journal":"International journal of clinical and experimental pathology, 8(5), 4662-72","doi":null,"pmid":"26191156","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02675","title":"Th17 polarization of memory Th cells in early arthritis: the vasoactive intestinal peptide effect.","authors":"Jimeno, Rebeca; Leceta, Javier; Garín, Marina; Ortiz, Ana M; Mellado, Mario; Rodríguez-Frade, Jose Miguel; Martínez, Carmen; Pérez-García, Selene; Gomariz, Rosa P; Juarranz, Yasmina","year":2015,"journal":"Journal of leukocyte biology, 98(2), 257-69","doi":"10.1189/jlb.3A0714-327R","pmid":"25957307","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02676","title":"Injection-Site Nodules Associated With the Use of Exenatide Extended-Release Reported to the U.S. Food and Drug Administration Adverse Event Reporting System.","authors":"Jones, S Christopher; Ryan, Debra L; Pratt, Valerie S W; Niak, Ali; Brinker, Allen D","year":2015,"journal":"Diabetes spectrum : a publication of the American Diabetes Association, 28(4), 283-8","doi":"10.2337/diaspect.28.4.283","pmid":"26597395","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02677","title":"Substance P induces cardioprotection in ischemia-reperfusion via activation of AKT.","authors":"Jubair, Shaiban; Li, Jianping; Dehlin, Heather M; Manteufel, Edward J; Goldspink, Paul H; Levick, Scott P; Janicki, Joseph S","year":2015,"journal":"American journal of physiology. Heart and circulatory physiology, 309(4), H676-84","doi":"10.1152/ajpheart.00200.2015","pmid":"26071541","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Substance P reduced ischemia-related lactate dehydrogenase release (a marker of cell damage) in both isolated heart preparations and hypoxic left ventricular tissue slices. It also reduced both apoptosis (programmed cell death) and necrosis (cell death from damage) in hypoxic tissue. Substance P induced AKT phosphorylation — a key step in cell survival signaling. Both the AKT inhibitor LY294002 and the NK-1 receptor antagonist L732138 blocked AKT phosphorylation and eliminated substance P's cardioprotective effect, confirming the NK-1 receptor/AKT mechanism.","whyItMatters":"Ischemia-reperfusion injury is a major cause of heart damage during and after heart attacks, and current therapies have limited ability to prevent it. Discovering that substance P — a peptide already present in the body — can directly protect heart cells through a well-characterized survival pathway opens a potential new therapeutic approach. The finding that this works through direct cellular effects (not just blood vessel dilation) expands our understanding of how peptides could be used in cardiac emergencies.","specificNumbers":"","methodology":"Seven-week-old male Sprague-Dawley rats were used. Researchers tested substance P's cardioprotective effects using two preparations: (1) isolated hearts subjected to ischemia-reperfusion, and (2) left ventricular tissue slice cultures exposed to short-term hypoxia without reperfusion. Cell damage was measured by lactate dehydrogenase release, and cell death was assessed for both apoptosis and necrosis. The NK-1 receptor antagonist L732138 and AKT inhibitor LY294002 were used to confirm the signaling pathway.","limitations":"This is an animal study using isolated rat hearts and tissue slices, which may not fully replicate the complexity of human cardiac ischemia-reperfusion. The preparations lack the neurohormonal and immune responses that occur in a living organism. Dosing and timing parameters that work in isolated preparations may not translate directly to clinical use. No long-term functional outcomes were assessed."},{"rthcId":"RPEP-02678","title":"Cross-linking of sodium caseinate-structured emulsion with transglutaminase alters postprandial metabolic and appetite responses in healthy young individuals.","authors":"Juvonen, Kristiina R; Macierzanka, Adam; Lille, Martina E; Laaksonen, David E; Mykkänen, Hannu M; Niskanen, Leo K; Pihlajamäki, Jussi; Mäkelä, Kari A; Mills, Clare E N; Mackie, Alan R; Malcolm, Paul; Herzig, Karl-Heinz; Poutanen, Kaisa S; Karhunen, Leila J","year":2015,"journal":"The British journal of nutrition, 114(3), 418-29","doi":"10.1017/S0007114515001737","pmid":"26159899","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02679","title":"Ghrelin receptor in Japanese fire belly newt, Cynops pyrrhogaster.","authors":"Kaiya, Hiroyuki; Kangawa, Kenji; Miyazato, Mikiya","year":2015,"journal":"Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology, 189, 15-22","doi":"10.1016/j.cbpb.2015.07.001","pmid":"26172570","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02680","title":"Influence of Dimerization of Lipopeptide Laur-Orn-Orn-Cys-NH2 and an N-terminal Peptide of Human Lactoferricin on Biological Activity.","authors":"Kamysz, Elżbieta; Sikorska, Emilia; Dawgul, Małgorzata; Tyszkowski, Rafał; Kamysz, Wojciech","year":2015,"journal":"International journal of peptide research and therapeutics, 21(1), 39-46","doi":null,"pmid":"25642159","tags":["antimicrobial-peptides","peptide-design"],"studyType":"in-vitro","evidenceStrength":"early-research","keyFinding":"Linking two different antimicrobial peptides together through a disulfide bond (heterodimerization) produced a compound that retained strong antibacterial activity while dramatically reducing toxicity to human cells. Specifically, the heterodimer of a lipopeptide (Laur-Orn-Orn-Cys-NH2) and an N-terminal fragment of human lactoferricin was nearly as active against bacteria as the more potent individual monomer, but was much less toxic (less hemolytic).\n\nHowever, both homo- and heterodimerization reduced or eliminated antifungal activity, suggesting the structural changes that improve the safety profile against bacteria may compromise activity against fungi.","whyItMatters":"One of the biggest challenges in developing antimicrobial peptides as drugs is that many of them are toxic to human cells at the concentrations needed to kill bacteria. This study demonstrates a clever strategy — linking two different peptides via a disulfide bond — that preserves antibacterial punch while reducing collateral damage. If this approach generalizes, it could help solve the toxicity problem that has stalled many antimicrobial peptide drug candidates.","specificNumbers":"2 peptide monomers linked via S-S bond · Heterodimer retained near-monomer antibacterial activity · Significantly reduced hemolytic toxicity · Antifungal activity lost upon dimerization","methodology":"In vitro study synthesizing homo- and heterodimeric versions of a lipopeptide and a lactoferricin fragment linked by intermolecular disulfide bonds. Compounds were tested for antimicrobial activity against bacteria and fungi, and for hemolytic (red blood cell-destroying) activity as a measure of toxicity to human cells.","limitations":"This is an in vitro study with no animal or human data. The loss of antifungal activity limits the approach's versatility. Only a limited number of bacterial and fungal species were tested. The stability and pharmacokinetics of the disulfide-linked dimer in biological environments are unknown. Manufacturing complexity of dimeric peptides may be higher than monomers."},{"rthcId":"RPEP-02681","title":"New therapeutic approach to heart failure due to myocardial infarction based on targeting growth hormone-releasing hormone receptor.","authors":"Kanashiro-Takeuchi, Rosemeire M; Szalontay, Luca; Schally, Andrew V; Takeuchi, Lauro M; Popovics, Petra; Jaszberenyi, Miklos; Vidaurre, Irving; Zarandi, Marta; Cai, Ren-Zhi; Block, Norman L; Hare, Joshua M; Rick, Ferenc G","year":2015,"journal":"Oncotarget, 6(12), 9728-39","doi":null,"pmid":"25797248","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Three GHRH agonists — JI-38, MR-356, and MR-409 — reduced myocardial infarct size in rats after four weeks of treatment compared to placebo. The treated hearts showed increased numbers of cardiac c-kit+ progenitor cells (cardiac stem cells), more cellular mitotic divisions (active cell regeneration), and higher vascular density (new blood vessel formation).\n\nOne week after heart attack, MR-409 significantly reduced plasma levels of four inflammatory cytokines: IL-2, IL-6, IL-10, and TNF-α compared to placebo. Gene expression analysis revealed that MR-409 treatment inhibited pro-apoptotic molecules (cell death signals) and pro-fibrotic pathways (scarring) while elevating bone morphogenetic proteins involved in tissue repair. In cell culture, GHRH agonists decreased harmful calcium influx and improved cell survival under nutrient deprivation conditions.","whyItMatters":"Heart failure after heart attack is a leading cause of death worldwide, and current treatments only slow progression rather than repair damage. GHRH agonists represent a new peptide-based approach that addresses multiple aspects of cardiac repair simultaneously: reducing inflammation, preventing scar formation, activating cardiac stem cells, and promoting new blood vessel growth. This multi-mechanism action could make them more effective than single-target therapies.","specificNumbers":"","methodology":"In vitro, H9c2 cardiac cells were cultured in serum-free medium to mimic nutrient deprivation after heart attack. GHRH agonists were tested for effects on calcium influx and cell survival. In vivo, rats with surgically induced myocardial infarction were treated with GHRH agonist peptides or placebo for four weeks. Outcomes included infarct size measurement, counting of c-kit+ cardiac progenitor cells and mitotic divisions, vascular density assessment, plasma cytokine levels (ELISA), and gene expression profiling for apoptotic, fibrotic, and repair pathways.","limitations":"This is a preclinical study in rats with surgically induced heart attacks — a model that doesn't fully replicate human coronary disease. The four-week treatment period is relatively short, and long-term effects on cardiac remodeling are unknown. Growth hormone-related peptides could potentially stimulate undesirable cell growth in other tissues, which needs safety evaluation. The study used multiple agonists with varying potencies but didn't establish optimal dosing for clinical translation. Gene expression changes don't guarantee functional cardiac improvement."},{"rthcId":"RPEP-02682","title":"Bench-to-bedside pharmacology of adrenomedullin.","authors":"Kato, Johji; Kitamura, Kazuo","year":2015,"journal":"European journal of pharmacology, 764, 140-148","doi":"10.1016/j.ejphar.2015.06.061","pmid":"26144371","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02683","title":"Synthesis of histone proteins by CPE ligation using a recombinant peptide as the C-terminal building block.","authors":"Kawakami, Toru; Yoshikawa, Ryo; Fujiyoshi, Yuki; Mishima, Yuichi; Hojo, Hironobu; Tajima, Shoji; Suetake, Isao","year":2015,"journal":"Journal of biochemistry, 158(5), 403-11","doi":"10.1093/jb/mvv056","pmid":"26002961","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02684","title":"Substance P Receptor Antagonist Suppresses Inflammatory Cytokine Expression in Human Disc Cells.","authors":"Kepler, Christopher K; Markova, Dessislava Z; Koerner, John D; Mendelis, Joseph; Chen, Chiu-Ming; Vaccaro, Alexander R; Risbud, Makarand V; Albert, Todd J; Anderson, D Greg","year":2015,"journal":"Spine, 40(16), 1261-9","doi":"10.1097/BRS.0000000000000954","pmid":"25929203","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The NK1R antagonist (L-760735) suppressed Substance P-induced expression of IL-1β, IL-6, and IL-8 in human disc cells in a dose-dependent manner, confirming that NK1R is responsible for Substance P's pro-inflammatory effects in disc tissue.\n\nSubstance P stimulation increased phosphorylation of p38-MAPK and ERK1/2 but did not activate NF-κB p65 — a surprising finding since NF-κB is often the assumed inflammatory pathway. Specific inhibitors of p38 (SB203580) and ERK1/2 (PD98059) reduced SP-induced IL-6 production, confirming these pathways as the relevant signaling cascades. All three neurokinin receptors (NK1R, NK2R, NK3R) were detected in both annulus fibrosus and nucleus pulposus disc cells.","whyItMatters":"Chronic back pain from disc degeneration affects hundreds of millions of people worldwide, and current treatments (painkillers, steroids, surgery) are often inadequate. This study identifies a specific molecular target — the NK1 receptor — that could be blocked to reduce inflammation directly in disc tissue. Unlike broad anti-inflammatory drugs, targeting Substance P signaling could address the root cause of disc inflammation without widespread side effects.","specificNumbers":"","methodology":"In vitro laboratory study using human intervertebral disc cells (both annulus fibrosus and nucleus pulposus). Cells were expanded in monolayer culture, then suspended in alginate beads to maintain a 3D environment. Cells were treated with the NK1R antagonist L-760735 at different concentrations, then stimulated with Substance P. Gene expression of inflammatory cytokines (IL-1β, IL-6, IL-8) was measured by quantitative RT-PCR. Signaling pathway activation was assessed by Western blot for phosphorylated p38-MAPK, ERK1/2, and NF-κB p65. Specific pathway inhibitors confirmed the signaling mechanisms.","limitations":"This is an in vitro study using cultured human disc cells in alginate beads, which doesn't fully replicate the complex environment of a living disc. The study tested only one NK1R antagonist (L-760735). Cell culture conditions may alter receptor expression and signaling compared to in vivo. The clinical translation — whether blocking NK1R in disc tissue would reduce pain in patients — remains untested. The source and condition of the human disc cells (healthy vs. degenerated) could affect results."},{"rthcId":"RPEP-02685","title":"The role of pancreatic polypeptide in the regulation of energy homeostasis.","authors":"Khandekar, Neeta; Berning, Britt A; Sainsbury, Amanda; Lin, Shu","year":2015,"journal":"Molecular and cellular endocrinology, 418 Pt 1, 33-41","doi":"10.1016/j.mce.2015.06.028","pmid":"26123585","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02686","title":"Substance P stimulates proliferation of spinal neural stem cells in spinal cord injury via the mitogen-activated protein kinase signaling pathway.","authors":"Kim, Kyoung-Tae; Kim, Hye-Jeong; Cho, Dae-Chul; Bae, Jae-Sung; Park, Seung-Won","year":2015,"journal":"The spine journal : official journal of the North American Spine Society, 15(9), 2055-65","doi":"10.1016/j.spinee.2015.04.032","pmid":"25921821","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Substance P significantly increases proliferation of spinal cord-derived neural stem/progenitor cells (SC-NSPCs) both in vitro and in vivo after spinal cord injury. This proliferative effect is mediated through activation of the MAP kinase signaling pathway, particularly phosphorylated ERK and p38 proteins.","whyItMatters":"Understanding how Substance P stimulates spinal stem cell growth could lead to new therapies for spinal cord injuries by promoting neural regeneration and functional recovery.","specificNumbers":"","methodology":"The study used a randomized animal model of spinal cord injury with intrathecal infusion of Substance P or its antagonist. In vitro assays measured SC-NSPC proliferation with varying SP concentrations. Immunostaining and immunoblotting assessed cell proliferation and MAP kinase protein activation.","limitations":"The study was conducted in rats, so results may not fully translate to humans. The exact long-term functional benefits of increased stem cell proliferation were not assessed."},{"rthcId":"RPEP-02687","title":"Evaluation of thymosin α 1 in nonclinical models of the immune-suppressing indications melanoma and sepsis.","authors":"King, Robert S; Tuthill, Cynthia","year":2015,"journal":"Expert opinion on biological therapy, 15 Suppl 1, S41-9","doi":"10.1517/14712598.2015.1008446","pmid":"25643200","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Thymosin alpha 1 treatment led to a 32% reduction in lung metastases and a 34-46% decrease in tumor growth in melanoma mouse models. In a sepsis model, it showed a positive trend towards increased survival and reduced bacterial load, with effects on biomarkers indicating immune modulation.","whyItMatters":"These results highlight thymosin alpha 1's potential as an immune-modulating therapy for diseases characterized by immune suppression, such as melanoma and sepsis. It may enhance treatment options either alone or alongside other immunotherapies.","specificNumbers":"","methodology":"The study used three nonclinical mouse models: a lung metastasis B16 melanoma model, a B16 tumor growth model, and a cecal-ligation and puncture (CLP) sepsis model. Thymosin alpha 1 was administered alone or combined with an anti-PD-1 antibody, and outcomes such as metastases, tumor size, survival, bacterial load, and biomarkers were measured.","limitations":"The study was conducted in mouse models, which may not fully replicate human disease. The evidence strength and detailed dosing information were not provided, limiting direct clinical applicability."},{"rthcId":"RPEP-02688","title":"The Female Sexual Response: Current Models, Neurobiological Underpinnings and Agents Currently Approved or Under Investigation for the Treatment of Hypoactive Sexual Desire Disorder.","authors":"Kingsberg, Sheryl A; Clayton, Anita H; Pfaus, James G","year":2015,"journal":"CNS drugs, 29(11), 915-33","doi":"10.1007/s40263-015-0288-1","pmid":"26519340","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"HSDD likely results from an imbalance between excitatory and inhibitory neurobiological pathways regulating sexual desire, involving neurotransmitters like dopamine, norepinephrine, serotonin, and oxytocin. Flibanserin is the first FDA-approved drug targeting these pathways for premenopausal women with HSDD, with other agents under investigation.","whyItMatters":"This review highlights the complexity of female sexual desire and the neurobiological basis of HSDD, guiding development of targeted therapies that can improve women's sexual health and quality of life.","specificNumbers":"","methodology":"This is a review article summarizing current models of female sexual response, neurobiological mechanisms, and available or investigational treatments for HSDD based on existing research and clinical data.","limitations":"The article is a review and does not present new experimental data; evidence strength and study types vary across cited research."},{"rthcId":"RPEP-02689","title":"Assessment of plasma brain-derived neurotrophic factor (BDNF), activity-dependent neurotrophin protein (ADNP) and vasoactive intestinal peptide (VIP) concentrations in treatment-naïve humans with multiple sclerosis.","authors":"Kochanowski, Jan; Uchman, Dorota; Litwiniuk, Anna; Kalisz, Malgorzata; Wolinska-Witort, Ewa; Martynska, Lidia; Baranowska, Boguslawa; Bik, Wojciech","year":2015,"journal":"Neuro endocrinology letters, 36(2), 148-52","doi":null,"pmid":"26071584","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Plasma concentrations of BDNF, ADNP, and VIP in 31 treatment-naïve, newly diagnosed MS patients did not differ significantly from those in 36 healthy controls. Additionally, no correlations were found between these neurotrophic factors and inflammatory cytokines (IL-6, IL-10, TNF-α), C-reactive protein levels, or disability status as measured by the Expanded Disability Status Scale (EDSS).\n\nThis null result is informative — it suggests that in the earliest stages of MS, before treatment intervention, these neuroprotective peptides have not yet been detectably altered in peripheral blood.","whyItMatters":"VIP is a neuroprotective peptide with known anti-inflammatory and immune-modulating properties that has been investigated as a potential MS treatment. Understanding whether its levels are altered in early, untreated MS helps determine if VIP deficiency contributes to disease onset or if changes occur later with disease progression and treatment. This null finding narrows the window for when VIP-related changes might occur in MS.","specificNumbers":"","methodology":"This was a cross-sectional study comparing 31 untreated MS patients with 36 healthy controls from a single hospital center. Plasma BDNF and ADNP were measured using ELISA, VIP was measured by radioimmunoassay (RIA), and inflammatory cytokines (IL-6, IL-10, TNF-α) were assessed with ELISA. Statistical analyses compared protein levels between groups and examined correlations with inflammatory markers and EDSS disability scores.","limitations":"The small sample size (31 patients, 36 controls) limits statistical power to detect subtle differences. The study was cross-sectional and from a single center, preventing assessment of how these peptide levels change over time with disease progression. Plasma measurements may not reflect levels within the central nervous system, where MS pathology occurs. The study measured only newly diagnosed patients, so changes that develop with disease duration remain unknown."},{"rthcId":"RPEP-02690","title":"Novel delivery systems for improving the clinical use of peptides.","authors":"Kovalainen, Miia; Mönkäre, Juha; Riikonen, Joakim; Pesonen, Ullamari; Vlasova, Maria; Salonen, Jarno; Lehto, Vesa-Pekka; Järvinen, Kristiina; Herzig, Karl-Heinz","year":2015,"journal":"Pharmacological reviews, 67(3), 541-61","doi":"10.1124/pr.113.008367","pmid":"26023145","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"This review maps the landscape of peptide drug delivery challenges and solutions. The central problem is that peptide drugs have poor bioavailability — they don't cross biological membranes well and break down quickly. While subcutaneous injection is the standard delivery method, most formulations don't provide sustained release, requiring frequent injections. The authors highlight porous silicon as a particularly promising carrier material that can hold exceptionally high peptide payloads and be tuned to release peptides slowly over time.","whyItMatters":"Peptide drugs are among the most specific and least toxic therapeutics available, but the delivery problem has limited their widespread use for decades. Every major peptide drug — from insulin to semaglutide — has had to solve the same fundamental challenge of getting the molecule into the bloodstream intact. This review provides a comprehensive overview of the technologies being developed to make peptide drugs more practical, comfortable, and effective for patients.","specificNumbers":"","methodology":"The authors conducted a comprehensive literature review covering peptidergic drugs currently in clinical use, parenteral delivery systems, and emerging nanotechnology approaches. They gave special emphasis to their own work developing porous silicon as a peptide delivery material, summarizing its biodegradability, biocompatibility, and payload capacity.","limitations":"As a review from 2015, it predates several major advances in peptide delivery including the SNAC-based oral semaglutide formulation (approved 2019) and newer long-acting injectable formulations. The emphasis on porous silicon reflects the authors' own research focus, which may give it disproportionate attention relative to other emerging technologies."},{"rthcId":"RPEP-02691","title":"A double-blind, placebo-controlled, randomised, clinical study on the effectiveness of collagen peptide on osteoarthritis.","authors":"Kumar, Suresh; Sugihara, Fumihito; Suzuki, Keiji; Inoue, Naoki; Venkateswarathirukumara, Sriraam","year":2015,"journal":"Journal of the science of food and agriculture, 95(4), 702-7","doi":"10.1002/jsfa.6752","pmid":"24852756","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Oral supplementation with collagen peptides derived from pork skin and bovine bone significantly reduced pain and improved joint function and quality of life scores in knee osteoarthritis patients over 13 weeks compared to placebo.","whyItMatters":"This study supports collagen peptides as a safe, nutritional supplement option to manage osteoarthritis symptoms and improve joint health, potentially reducing reliance on pharmaceutical pain treatments.","specificNumbers":"","methodology":"A double-blind, placebo-controlled, randomized clinical trial was conducted where patients with knee osteoarthritis received either collagen peptides from pork skin or bovine bone, or placebo, for 13 weeks. Outcomes were measured using WOMAC, VAS, and quality of life scores.","limitations":"The study does not specify sample size or long-term effects beyond 13 weeks, and the exact strength of evidence is not detailed, limiting generalizability."},{"rthcId":"RPEP-02692","title":"Highly angiogenic peptide nanofibers.","authors":"Kumar, Vivek A; Taylor, Nichole L; Shi, Siyu; Wang, Benjamin K; Jalan, Abhishek A; Kang, Marci K; Wickremasinghe, Navindee C; Hartgerink, Jeffrey D","year":2015,"journal":"ACS nano, 9(1), 860-8","doi":"10.1021/nn506544b","pmid":"25584521","tags":[],"studyType":"in-vivo","evidenceStrength":"low-moderate","keyFinding":"Researchers created a self-assembling peptide nanofiber hydrogel that can be injected by syringe and rapidly promotes blood vessel formation (angiogenesis) in living tissue. Within three weeks in rats, the hydrogel was infiltrated by blood-forming and tissue-building cells, formed a robust mature vascular network, showed no fibrous encapsulation (scar tissue walling off the implant), and was completely resorbed into the surrounding tissue.\n\nThe peptide design incorporated two key features: cell-mediated degradation sites (so the body's own cells break it down naturally) and proangiogenic sequences (that actively signal for new blood vessel growth). The injectable delivery eliminates the need for surgical implantation.","whyItMatters":"One of the biggest problems in tissue engineering is getting blood vessels to grow into implanted scaffolds — without blood supply, cells inside the scaffold die. Most artificial scaffolds also trigger immune rejection, forming scar tissue capsules that wall them off. This peptide hydrogel solves both problems: it actively recruits blood vessels and integrates seamlessly without scarring, then dissolves once the tissue is regenerated. This could transform treatment of ischemic tissue disease (heart attacks, peripheral artery disease, chronic wounds).","specificNumbers":"Mature vascular network in 3 weeks · 0 fibrous encapsulation · Injectable via syringe · Scaffold size threshold: 200–500 µm · Complete tissue resorption by 3 weeks","methodology":"Researchers designed a peptide sequence that self-assembles into nanofibers forming a hydrogel, incorporating cell-mediated degradation sites and proangiogenic motifs. The hydrogel was injected subcutaneously into female Wistar rats and evaluated over three weeks for cellular infiltration (hematopoietic and mesenchymal cells), vascular network formation, immune response (fibrous encapsulation), and scaffold degradation/tissue integration.","limitations":"This is a preclinical animal study in rats — human tissue responses may differ. The subcutaneous injection site does not replicate the complex environment of ischemic organs like the heart. Three-week follow-up may be too short to assess long-term tissue outcomes. Specific quantitative measures of vascular density and mechanical properties are not detailed in the abstract. No comparison to existing scaffold materials was described."},{"rthcId":"RPEP-02693","title":"Self-assembling multidomain peptides tailor biological responses through biphasic release.","authors":"Kumar, Vivek A; Taylor, Nichole L; Shi, Siyu; Wickremasinghe, Navindee C; D'Souza, Rena N; Hartgerink, Jeffrey D","year":2015,"journal":"Biomaterials, 52, 71-8","doi":"10.1016/j.biomaterials.2015.01.079","pmid":"25818414","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A self-assembling multidomain peptide hydrogel delivered cytokines in a biphasic pattern that controlled immune cell behavior in both space and time. The nanofibrous scaffold recruited monocytes and macrophages, promoted their polarization toward a healing (M2) phenotype without creating inflammation, and was completely resorbed within 14 days of subcutaneous implantation. The injectable material recovered after shear stress, making it suitable for injection-based delivery.","whyItMatters":"Controlling the immune response at a wound or implant site is crucial for healing. This peptide hydrogel achieves something difficult — recruiting immune cells and guiding them toward repair rather than inflammation — using a fully synthetic, injectable, and biodegradable peptide material. It demonstrates the potential of designed peptides as programmable biomaterials.","specificNumbers":"Biphasic cytokine release · macrophage infiltration by day 3 · complete scaffold resorption by day 14 · M2 pro-resolution environment · injectable with shear recovery","methodology":"Multidomain peptides were synthesized and self-assembled into nanofibrous hydrogels loaded with cytokines. In vitro, THP-1 monocyte/macrophage activation and polarization were assessed. In vivo, scaffolds were injected subcutaneously in Wistar rats and evaluated for macrophage infiltration, polarization, and scaffold degradation at multiple time points up to 14 days.","limitations":"Subcutaneous implantation is a simplified model — actual tissue engineering applications (bone, cartilage, etc.) present different challenges. Specific cytokines used and quantitative release kinetics are not detailed in the abstract. Long-term outcomes beyond 14 days (actual tissue regeneration) were not assessed. Only one animal model was used."},{"rthcId":"RPEP-02694","title":"Effect of Intra-articular Injection of AOD9604 with or without Hyaluronic Acid in Rabbit Osteoarthritis Model.","authors":"Kwon, Dong Rak; Park, Gi Young","year":2015,"journal":"Annals of clinical and laboratory science, 45(4), 426-32","doi":null,"pmid":"26275694","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02695","title":"Effects of two dietary fibers as part of ready-to-eat cereal (RTEC) breakfasts on perceived appetite and gut hormones in overweight women.","authors":"Lafond, David W; Greaves, Kathryn A; Maki, Kevin C; Leidy, Heather J; Romsos, Dale R","year":2015,"journal":"Nutrients, 7(2), 1245-66","doi":"10.3390/nu7021245","pmid":"25689743","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Consumption of 15 g of enzyme-hydrolyzed wheat arabinoxylan (AXOS) or intact flax arabinoxylan (FLAX) fibers in ready-to-eat cereals increased postprandial GLP-1 and PYY hormone concentrations compared to isocaloric low-fiber controls, but did not alter perceived appetite or subsequent energy intake in overweight women.","whyItMatters":"Understanding how different dietary fibers affect gut hormones and appetite can inform the development of functional foods aimed at weight management. This study highlights that changes in satiety hormones do not always translate to reduced food intake.","specificNumbers":"","methodology":"Two randomized, double-blind, crossover trials were conducted with overweight women consuming ready-to-eat cereals containing low or high fiber (AXOS or FLAX). Appetite ratings and blood samples for gut hormones were collected, and an ad libitum lunch was offered 4 hours later to measure energy intake.","limitations":"The study only measured short-term effects after a single meal and included a relatively small sample of overweight women, limiting generalizability and long-term conclusions."},{"rthcId":"RPEP-02696","title":"Ancestral vertebrate complexity of the opioid system.","authors":"Larhammar, Dan; Bergqvist, Christina; Sundström, Görel","year":2015,"journal":"Vitamins and hormones, 97, 95-122","doi":"10.1016/bs.vh.2014.11.001","pmid":"25677769","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The opioid system in vertebrates originated from a single opioid precursor and receptor gene, which duplicated through two whole genome duplications to produce four peptide precursors (endorphin, enkephalins, dynorphins, nociceptin) and four receptor types (delta, kappa, mu, and nociceptin/orphanin receptor). A third genome duplication in teleost fishes further expanded these gene copies, indicating a more complex opioid system in these species than in mammals.","whyItMatters":"Understanding the evolutionary complexity of the opioid system provides insights into its functional diversity and can inform biomedical research on opioid receptors and peptides, potentially aiding drug development and pain management.","specificNumbers":"","methodology":"The study combined sequence comparisons of opioid peptides and receptors with chromosomal gene location data across various vertebrate species, including basal fish like coelacanth and spotted gar, to reconstruct the evolutionary history of the opioid system.","limitations":"The study does not specify experimental validation of receptor function and relies primarily on genomic and sequence analysis; the exact functional implications of gene duplications remain to be fully explored."},{"rthcId":"RPEP-02697","title":"Group A Streptococcal M1 Protein Sequesters Cathelicidin to Evade Innate Immune Killing.","authors":"LaRock, Christopher N; Döhrmann, Simon; Todd, Jordan; Corriden, Ross; Olson, Joshua; Johannssen, Timo; Lepenies, Bernd; Gallo, Richard L; Ghosh, Partho; Nizet, Victor","year":2015,"journal":"Cell host & microbe, 18(4), 471-7","doi":"10.1016/j.chom.2015.09.004","pmid":"26468750","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The M1 protein on hypervirulent M1T1 group A Streptococcus binds and neutralizes the antimicrobial peptide LL-37 and its precursor hCAP-18, preventing LL-37 maturation and function. This interaction enhances bacterial resistance to neutrophil killing and contributes to virulence in a mouse infection model.","whyItMatters":"Understanding how bacteria evade immune peptides like LL-37 can guide development of new treatments that restore immune defense or target bacterial evasion mechanisms.","specificNumbers":"","methodology":"The study used biochemical assays to demonstrate binding between M1 protein and LL-37/hCAP-18, functional assays to assess bacterial survival against neutrophils and neutrophil extracellular traps, and a murine skin infection model to evaluate virulence.","limitations":"The study does not specify the exact clinical relevance across diverse human infections, and the evidence strength and study type are not detailed, limiting assessment of generalizability."},{"rthcId":"RPEP-02698","title":"A two-component 'double-click' approach to peptide stapling.","authors":"Lau, Yu Heng; Wu, Yuteng; de Andrade, Peterson; Galloway, Warren R J D; Spring, David R","year":2015,"journal":"Nature protocols, 10(4), 585-94","doi":"10.1038/nprot.2015.033","pmid":"25763835","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The double-click stapling approach efficiently stabilizes linear diazido peptides into α-helical conformations via bis-triazole linkages, enhancing binding affinity, proteolytic stability, and cellular activity of peptide inhibitors.","whyItMatters":"This method provides a modular and efficient way to improve peptide stability and bioactivity, which is crucial for developing peptide-based therapeutics and research tools.","specificNumbers":"","methodology":"The study optimized a chemical reaction between 1,3-dialkynylbenzene linkers and azidoornithine-containing peptides under Cu(I) catalysis to create side chain-cyclized peptides. The protocol includes peptide synthesis, double-click stapling, purification, and confirmation steps completed within approximately 48 hours.","limitations":"The study does not specify in vivo efficacy or long-term stability data, and the evidence strength and study type are not clearly defined."},{"rthcId":"RPEP-02699","title":"Cholecystokinin expression in the β-cell leads to increased β-cell area in aged mice and protects from streptozotocin-induced diabetes and apoptosis.","authors":"Lavine, Jeremy A; Kibbe, Carly R; Baan, Mieke; Sirinvaravong, Sirinart; Umhoefer, Heidi M; Engler, Kimberly A; Meske, Louise M; Sacotte, Kaitlyn A; Erhardt, Daniel P; Davis, Dawn Belt","year":2015,"journal":"American journal of physiology. Endocrinology and metabolism, 309(10), E819-28","doi":"10.1152/ajpendo.00159.2015","pmid":"26394663","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Transgenic mice expressing cholecystokinin specifically in pancreatic β-cells showed increased β-cell area with age and were resistant to streptozotocin-induced diabetes due to reduced β-cell apoptosis. Additionally, CCK overexpression in cultured β-cells protected them from cytokine-induced apoptosis, indicating a protective autocrine/paracrine role of CCK in β-cell survival.","whyItMatters":"Understanding how CCK protects β-cells from apoptosis could lead to new diabetes treatments that preserve insulin-producing cells. Since CCK receptor agonists are being explored for obesity and diabetes, this study highlights their potential to directly safeguard β-cells.","specificNumbers":"","methodology":"Researchers created a transgenic mouse model (MIP-CCK) that expresses CCK in pancreatic β-cells under lean conditions. They assessed β-cell area and apoptosis in aged mice and after streptozotocin treatment, a chemical that induces diabetes. They also tested CCK overexpression effects in cultured β-cells exposed to cytokines.","limitations":"The study was conducted in mice, so results may not fully translate to humans. The exact signaling mechanisms by which CCK protects β-cells were not fully elucidated. The evidence strength and study type were not specified."},{"rthcId":"RPEP-02700","title":"Substance P promotes wound healing in diabetes by modulating inflammation and macrophage phenotype.","authors":"Leal, Ermelindo C; Carvalho, Eugénia; Tellechea, Ana; Kafanas, Antonios; Tecilazich, Francesco; Kearney, Cathal; Kuchibhotla, Sarada; Auster, Michael E; Kokkotou, Efi; Mooney, David J; LoGerfo, Frank W; Pradhan-Nabzdyk, Leena; Veves, Aristidis","year":2015,"journal":"The American journal of pathology, 185(6), 1638-48","doi":"10.1016/j.ajpath.2015.02.011","pmid":"25871534","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Exogenous Substance P administration improved wound healing in diabetic mouse and rabbit models by inducing an acute inflammatory response and promoting macrophage polarization toward the M2 phenotype. Deficiency of Substance P or its receptor impaired wound healing, and diabetic skin showed reduced Substance P levels with increased degradation enzyme expression.\n\nCritically, the study demonstrated a dual problem in diabetic skin: Substance P gene expression was decreased while neutral endopeptidase (the enzyme that degrades SP) was increased at both gene and protein levels. This creates a Substance P deficit that locks diabetic wounds into persistent, non-healing inflammation rather than the normal acute-to-proliferative healing sequence.","whyItMatters":"Diabetic foot ulcers affect millions of people worldwide and are a leading cause of non-traumatic limb amputation. Current treatments are often inadequate because they don't address the underlying inflammatory dysfunction. This research identifies a specific molecular mechanism — Substance P depletion — driving chronic wound inflammation in diabetes, and demonstrates that replacing this peptide can restore normal healing. This could lead to topical peptide therapies for diabetic wounds.","specificNumbers":"","methodology":"Researchers used multiple animal models: diabetic mice and rabbits received exogenous Substance P treatment on skin wounds, while genetically modified mice lacking either Substance P or its receptor (neurokinin-1 receptor) were used to confirm the peptide's role in healing. The team measured SP gene expression, neutral endopeptidase levels, inflammatory markers, and macrophage phenotype (M1 vs. M2 polarization) throughout the wound healing process.","limitations":"This study was conducted entirely in animal models (mice and rabbits), which heal differently from humans — particularly in skin structure and immune response. Specific dosing, delivery methods, and long-term safety of Substance P treatment were not detailed in the abstract. The study also did not examine whether Substance P treatment could work in established chronic wounds versus newly created experimental wounds."},{"rthcId":"RPEP-02701","title":"Denosumab and teriparatide transitions in postmenopausal osteoporosis (the DATA-Switch study): extension of a randomised controlled trial.","authors":"Leder, Benjamin Z; Tsai, Joy N; Uihlein, Alexander V; Wallace, Paul M; Lee, Hang; Neer, Robert M; Burnett-Bowie, Sherri-Ann M","year":2015,"journal":"Lancet (London, England), 386(9999), 1147-55","doi":"10.1016/S0140-6736(15)61120-5","pmid":"26144908","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02702","title":"Effects of abaloparatide, a human parathyroid hormone-related peptide analog, on bone mineral density in postmenopausal women with osteoporosis.","authors":"Leder, Benjamin Z; O'Dea, Louis St L; Zanchetta, José R; Kumar, Prasana; Banks, Kathleen; McKay, Kathleen; Lyttle, C Richard; Hattersley, Gary","year":2015,"journal":"The Journal of clinical endocrinology and metabolism, 100(2), 697-706","doi":"10.1210/jc.2014-3718","pmid":"25393645","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02703","title":"The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance.","authors":"Lee, Changhan; Zeng, Jennifer; Drew, Brian G; Sallam, Tamer; Martin-Montalvo, Alejandro; Wan, Junxiang; Kim, Su-Jeong; Mehta, Hemal; Hevener, Andrea L; de Cabo, Rafael; Cohen, Pinchas","year":2015,"journal":"Cell metabolism, 21(3), 443-54","doi":"10.1016/j.cmet.2015.02.009","pmid":"25738459","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02704","title":"Distinct functions of opioid-related peptides and gastrin-releasing peptide in regulating itch and pain in the spinal cord of primates.","authors":"Lee, Heeseung; Ko, Mei-Chuan","year":2015,"journal":"Scientific reports, 5, 11676","doi":"10.1038/srep11676","pmid":"26119696","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The study mapped distinct neuropeptide-receptor systems for itch and pain in primate spinal cord:\n\n**Itch-inducing systems:**\n- β-endorphin (10-100 nmol) → mu-opioid receptor (MOP) → robust scratching\n- Gastrin-releasing peptide (1-10 nmol) → BB2 receptor → equal scratching\n- β-endorphin also attenuates inflammatory pain; GRP does not affect pain\n\n**Pain-inhibiting only (no itch):**\n- Enkephalins (100-1000 nmol) → pain inhibition\n- Nociceptin-orphanin FQ (3-30 nmol) → pain inhibition\n\n**Itch-inhibiting (no pain effect):**\n- Dynorphin A(1-17) (10-100 nmol) → kappa-opioid receptor (KOP) → suppresses both β-endorphin- and GRP-induced itch\n- Anti-itch effect reversed by KOP receptor antagonist nor-binaltorphimine","whyItMatters":"Chronic itch affects millions of people with conditions like eczema, liver disease, and kidney failure, and current treatments are limited. Opioid painkillers notoriously cause itching as a side effect. Understanding that separate neuropeptide pathways control itch and pain in primates — the closest model to humans — could enable development of anti-itch drugs that don't affect pain processing, and pain drugs that don't cause itch. The identification of the dynorphin A-KOP receptor system as a selective anti-itch pathway is particularly promising.","specificNumbers":"","methodology":"Awake, behaving rhesus monkeys (Macaca mulatta) received intrathecal (spinal) injections of various neuropeptides at different doses. Behavioral responses — scratching (itch) and pain behaviors — were quantified. Receptor antagonists were used to confirm which receptor mediated each effect. The dose-response relationships were established for each peptide.","limitations":"The study was conducted in nonhuman primates with intrathecal (spinal) peptide delivery, which is not a practical therapeutic route for most patients. The number of animals used is not specified in the abstract. While rhesus monkeys are the closest available model to humans, species differences in neuropeptide systems may exist. The study focused on acute itch and pain responses and did not assess chronic conditions."},{"rthcId":"RPEP-02705","title":"Semisynthetic protein nanoreactor for single-molecule chemistry.","authors":"Lee, Joongoo; Bayley, Hagan","year":2015,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 112(45), 13768-73","doi":"10.1073/pnas.1510565112","pmid":"26504203","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Incorporation of an unnatural amino acid with a terminal alkyne into the α-hemolysin pore enabled visualization of click chemistry at the single-molecule level, revealing a long-lived 4.5-second reaction intermediate. This semisynthetic protein nanoreactor approach expands the capability to study covalent chemistry inside protein pores.","whyItMatters":"This method allows direct observation of chemical reactions at the single-molecule level within a protein environment, providing new insights into reaction mechanisms and expanding tools for peptide and protein engineering research.","specificNumbers":"","methodology":"The study used solid-phase peptide synthesis to create the central segment of the α-hemolysin pore containing an unnatural amino acid, which was then ligated to recombinant polypeptides to form full-length monomers. These semisynthetic pores were assembled into heptamers and used to monitor single-molecule chemical reactions by measuring ionic current changes through the pore.","limitations":"The study focused on a single type of chemical reaction (click chemistry) and used a semisynthetic protein pore with only one modified subunit, which may limit generalizability to other reactions or fully synthetic systems."},{"rthcId":"RPEP-02706","title":"Is Oxytocin Application for Autism Spectrum Disorder Evidence-Based?","authors":"Lee, Seung Yup; Lee, Ah Rah; Hwangbo, Ram; Han, Juhee; Hong, Minha; Bahn, Geon Ho","year":2015,"journal":"Experimental neurobiology, 24(4), 312-24","doi":"10.5607/en.2015.24.4.312","pmid":"26713079","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review highlights oxytocin as a promising therapeutic agent for ASD due to its involvement in social behavior and genetic links to the disorder. However, current evidence is preliminary, and the validity of oxytocin treatment in humans requires further confirmation.","whyItMatters":"Identifying effective treatments targeting the underlying biology of ASD could improve social functioning and quality of life for affected individuals. Oxytocin’s potential role opens new avenues for therapeutic development.","specificNumbers":"","methodology":"This study conducted a thorough literature review focusing on oxytocin’s role in sociality, genetic markers related to ASD, and existing human trials assessing oxytocin treatment efficacy.","limitations":"The evidence is mostly preliminary and based on early-stage studies; the review does not include large-scale clinical trials or definitive conclusions on treatment efficacy."},{"rthcId":"RPEP-02707","title":"An open-label clinical trial of the effects of age and gender on the pharmacodynamics, pharmacokinetics and safety of the ghrelin receptor agonist anamorelin.","authors":"Leese, Philip T; Trang, John M; Blum, Robert A; de Groot, Eleanor","year":2015,"journal":"Clinical pharmacology in drug development, 4(2), 112-120","doi":null,"pmid":"26640742","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Anamorelin was rapidly absorbed with peak levels at 30-45 minutes and 2-4 hours post-dose. Females exhibited approximately 1.8-1.9 times higher mean AUC∞ values compared to males, but pharmacodynamic responses, including growth hormone increase, were similar between sexes and only slightly reduced in elderly subjects. No clinically significant safety issues were observed.","whyItMatters":"Understanding how age and gender affect anamorelin's pharmacokinetics and pharmacodynamics helps ensure safe and effective dosing for diverse patient populations in peptide-based therapies.","specificNumbers":"","methodology":"An open-label, single-center clinical trial enrolled three demographic cohorts of healthy subjects who received a single 25 mg oral dose of anamorelin HCl. Serial blood samples were collected over 24 hours to measure pharmacokinetics and circulating growth hormone levels, compared against a reference male cohort.","limitations":"Small cohort sizes (6-8 subjects per group) limit the statistical power to detect subtle differences, and the study only assessed single-dose administration in healthy volunteers."},{"rthcId":"RPEP-02708","title":"Antibacterial activity of synthetic peptides derived from lactoferricin against Escherichia coli ATCC 25922 and Enterococcus faecalis ATCC 29212.","authors":"León-Calvijo, María A; Leal-Castro, Aura L; Almanzar-Reina, Giovanni A; Rosas-Pérez, Jaiver E; García-Castañeda, Javier E; Rivera-Monroy, Zuly J","year":2015,"journal":"BioMed research international, 2015, 453826","doi":"10.1155/2015/453826","pmid":"25815317","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among multiple designed variants, peptides I.2 (RWQWRWQWR, a 9-amino-acid linear peptide) and I.4 (a branched tetravalent structure containing the RRWQWR sequence) showed the strongest activity. Against E. coli ATCC 25922, MIC values ranged from 4-33 μM; against E. faecalis ATCC 29212, MIC values were 10-33 μM.\n\nThese short synthetic peptides performed comparably or better than the full lactoferricin protein and longer derivative peptides like II.1 (15 amino acids) and IV.1 (24 amino acids). The common feature of the most active peptides was the RWQWR motif, suggesting this sequence is the core pharmacophore responsible for antibacterial activity. The peptides were synthesized with high yield and purity using standard solid-phase methods.","whyItMatters":"Antimicrobial peptides from natural sources like milk are promising antibiotic alternatives, but the full proteins are large, expensive to produce, and difficult to modify. Identifying the minimal active fragment — in this case, the RWQWR motif — makes it possible to create synthetic drugs that are cheaper, easier to manufacture, and more amenable to further optimization. The fact that both Gram-negative (E. coli) and Gram-positive (Enterococcus) bacteria were killed suggests broad-spectrum potential.","specificNumbers":"","methodology":"Peptides were designed using four modification strategies: incorporation of unnatural amino acids, chain shortening, chain elongation, and branched multivalent structures. Synthesis was performed by solid-phase peptide synthesis. Products were purified by reverse-phase HPLC and characterized by MALDI-TOF mass spectrometry. Antibacterial activity was determined by measuring minimum inhibitory concentrations (MIC) against E. coli ATCC 25922 and E. faecalis ATCC 29212 using standard microdilution methods.","limitations":"The study tested only two standard laboratory bacterial strains (ATCC reference strains), which may not represent the drug-resistant clinical isolates most in need of new treatments. No in vivo efficacy or toxicity data was presented, so the therapeutic window is unknown. Hemolytic activity (damage to red blood cells) — a common concern with cationic antimicrobial peptides — was not assessed. The mechanism of action was not investigated. Stability in biological fluids (serum, plasma) was not tested."},{"rthcId":"RPEP-02709","title":"Effect of immobilization stress on the appetite and stomach ghrelin expression in maternal mice.","authors":"Li, Bing; Xu, Yuemei; Pan, Danqing; Xiao, Qian; Gao, Qi; Chen, Xin; Peng, Xiuhua; Du, Yuling; Gao, Pengfei","year":2015,"journal":"International journal of clinical and experimental pathology, 8(12), 15993-9","doi":null,"pmid":"26884874","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Maternal immobilization stress during lactation decreased offspring body weight and food intake, increased stomach ghrelin protein expression, and altered hypothalamic expression of appetite-regulating genes, including decreased 5-HT2cR, 5-HT2bR, CRF, and POMC, and increased GHSR, NPY, and AgRP mRNA levels.","whyItMatters":"Understanding how maternal stress affects appetite hormones like ghrelin helps clarify mechanisms behind offspring growth issues and may guide interventions for stress-related developmental problems.","specificNumbers":"","methodology":"The study used maternal immobilization stress applied during lactation in mice. Offspring body weight and food intake were measured. Immunohistochemistry assessed stomach ghrelin protein levels, and real-time RT-PCR quantified hypothalamic mRNA expression of appetite-related hormones and receptors.","limitations":"The study does not specify sample size or control conditions in detail, and the exact causal pathways remain to be fully elucidated. The evidence strength and study type were not clearly defined."},{"rthcId":"RPEP-02710","title":"Thymosin alpha1 based immunomodulatory therapy for sepsis: a systematic review and meta-analysis.","authors":"Li, Congcong; Bo, Liyan; Liu, Qingqing; Jin, Faguang","year":2015,"journal":"International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases, 33, 90-6","doi":"10.1016/j.ijid.2014.12.032","pmid":"25532482","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02711","title":"Microneedle-Mediated Delivery of Copper Peptide Through Skin.","authors":"Li, Hairui; Low, Yong Sheng Jason; Chong, Hui Ping; Zin, Melvin T; Lee, Chi-Ying; Li, Bo; Leolukman, Melvina; Kang, Lifeng","year":2015,"journal":"Pharmaceutical research, 32(8), 2678-89","doi":"10.1007/s11095-015-1652-z","pmid":"25690343","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Microneedle pretreatment of human skin enabled dramatic GHK-Cu permeation: 134 ± 12 nanomoles of peptide and 705 ± 84 nanomoles of copper crossed the skin in 9 hours, versus essentially zero through intact skin. The depth and percentage of microneedle penetration were directly correlated with application force, which determined the degree of permeability enhancement. Histological assays and confocal microscopy confirmed well-defined channels through the stratum corneum. No skin irritation was observed.","whyItMatters":"GHK-Cu is one of the most well-studied regenerative peptides with demonstrated abilities to stimulate collagen synthesis and accelerate wound healing. However, topical application has been limited by near-zero skin absorption. Microneedle patches offer a practical, painless solution that creates only temporary microchannels healing within hours. This could finally make GHK-Cu an effective topical therapy.","specificNumbers":"","methodology":"Polymeric microneedle arrays were used to pretreat skin samples before GHK-Cu application. Two in vitro skin permeation models (including human skin) assessed drug delivery. Histological examination and confocal laser scanning microscopy characterized microconduits. Application force was varied to establish force-penetration-permeation relationships. Safety was assessed using keratinocyte cell viability assays and porcine skin irritation models.","limitations":"The study used in vitro skin models — actual in vivo absorption may differ due to blood flow and metabolism. The 9-hour permeation window may not reflect practical use patterns. Long-term safety of repeated microneedle use was not assessed. The biological activity of delivered GHK-Cu was not measured, only the quantity that permeated. Clinical efficacy was not tested."},{"rthcId":"RPEP-02712","title":"Total chemical synthesis of human interferon alpha-2b via native chemical ligation.","authors":"Li, Jing; Lehmann, Clara; Chen, Xishan; Romerio, Fabio; Lu, Wuyuan","year":2015,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 21(7), 554-60","doi":"10.1002/psc.2760","pmid":"25810135","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The researchers successfully synthesized the complete 165-amino-acid human interferon alpha-2b protein using native chemical ligation (NCL), which joins peptide fragments through chemical bonds at cysteine residues. The synthetic IFNα2b retained its biological properties.\n\nThis synthesis is an enabling step for mirror-image phage display — a technique where a D-amino acid version of the target protein is used to screen for L-peptide binders, which are then converted to D-peptide versions that resist protease degradation. The ultimate goal is to discover proteolysis-resistant D-peptide antagonists that block IFNα signaling.","whyItMatters":"Most peptide drugs are rapidly destroyed by enzymes in the body, limiting their use. D-peptides — made from mirror-image amino acids — are invisible to these enzymes and are therefore much more stable. Mirror-image phage display is a powerful technique for discovering D-peptide drugs, but it requires a chemically synthesized mirror-image version of the target protein. This synthesis of a 165-amino-acid protein demonstrates the feasibility of applying this approach to large targets like interferon.","specificNumbers":"","methodology":"The full 165-amino-acid IFNα2b protein was synthesized through native chemical ligation, a technique that chemically joins synthetic peptide fragments at cysteine residues to form native peptide bonds. The synthetic protein was then folded and tested for biological activity. The work represents the chemical manufacturing foundation needed for subsequent mirror-image phage display screening.","limitations":"The abstract confirms biological activity but does not detail specific functional assays or quantitative comparisons with recombinant IFNα2b. The D-enantiomer of IFNα2b has not yet been synthesized or used for mirror-image phage display — this paper represents the L-form synthesis as proof of feasibility. The yield and scalability of the synthesis are not discussed. No D-peptide inhibitors have been identified yet."},{"rthcId":"RPEP-02713","title":"PKCɛ mediates substance P inhibition of GABAA receptors-mediated current in rat dorsal root ganglion.","authors":"Li, Li; Zhao, Lei; Wang, Yang; Ma, Ke-Tao; Shi, Wen-Yan; Wang, Ying-Zi; Si, Jun-Qiang","year":2015,"journal":"Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban, 35(1), 1-9","doi":"10.1007/s11596-015-1380-y","pmid":"25673185","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Substance P suppresses GABA-activated inward currents and membrane depolarization in rat dorsal root ganglion neurons via activation of the NK1 receptor and the intracellular PLC-Ca²⁺-PKCε signaling cascade. This inhibition is concentration-dependent and specifically mediated by PKCε, not other PKC isoforms.","whyItMatters":"These findings clarify how substance P modulates inhibitory GABA signaling in peripheral sensory neurons, which is important for understanding mechanisms of pain and neurogenic inflammation. Targeting this pathway could inform new pain therapies.","specificNumbers":"","methodology":"The study used whole-cell patch-clamp and sharp electrode intracellular recording techniques on freshly dissociated rat dorsal root ganglion neurons to measure GABA-activated currents and membrane depolarization. Pharmacological agents were applied to identify receptor involvement and signaling pathways.","limitations":"The study was conducted in isolated rat neurons in vitro, which may not fully replicate in vivo conditions. The exact physiological relevance and effects in humans remain to be confirmed."},{"rthcId":"RPEP-02714","title":"Substance P spinal signaling induces glial activation and nociceptive sensitization after fracture.","authors":"Li, W-W; Guo, T-Z; Shi, X; Sun, Y; Wei, T; Clark, D J; Kingery, W S","year":2015,"journal":"Neuroscience, 310, 73-90","doi":"10.1016/j.neuroscience.2015.09.036","pmid":"26386297","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tibia fracture induces chronic activation of spinal microglia and astrocytes via Substance P release from C-fiber afferents, maintaining nociceptive sensitization. Inhibitors of glial activation or SP receptor antagonists partially reversed pain behaviors and glial activation.","whyItMatters":"Understanding how Substance P and glial cells maintain chronic pain after fractures could lead to targeted therapies for CRPS and other chronic pain conditions involving neuroinflammation.","specificNumbers":"","methodology":"The study used a rat tibia fracture model with casting, followed by behavioral pain assessments and pharmacological interventions targeting microglia, astrocytes, or SP receptors. Immunohistochemistry and PCR assessed glial activation. Additional experiments involved sciatic nerve C-fiber stimulation to mimic afferent SP release.","limitations":"The study was conducted in rodents, which may not fully replicate human CRPS. The exact clinical relevance and long-term effects of glial inhibitors require further investigation."},{"rthcId":"RPEP-02715","title":"Up-Regulation of the Biosynthesis and Release of Substance P through Wnt/β-Catenin Signaling Pathway in Rat Dorsal Root Ganglion Cells.","authors":"Li, Yu-Sang; Xi, Yang; Li, Xiao-Jun; Leng, Chang-Long; Jia, Mei-Mei; Zhang, Wei Kevin; Tang, He-Bin","year":2015,"journal":"PloS one, 10(6), e0129701","doi":"10.1371/journal.pone.0129701","pmid":"26054011","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Chronic constriction injury in rats significantly increased beta-catenin expression in dorsal root ganglion cells, which upregulated PPT-A mRNA and substance P release. Pharmacological activation of Wnt/beta-catenin signaling enhanced substance P biosynthesis, while COX-2 inhibition blocked this effect.","whyItMatters":"Understanding how beta-catenin regulates substance P helps clarify mechanisms behind chronic pain and inflammation, potentially guiding new peptide-targeted therapies.","specificNumbers":"","methodology":"The study used a rat chronic constriction injury model and cultured dorsal root ganglion cells to measure beta-catenin expression and substance P production. Pharmacological agents modulated Wnt/beta-catenin signaling and COX-2 activity to assess their roles.","limitations":"The study was conducted in rats and cultured cells, so results may not fully translate to humans. The exact clinical relevance and long-term effects remain to be explored."},{"rthcId":"RPEP-02716","title":"Growth hormone-releasing peptide-biotin conjugate stimulates myocytes differentiation through insulin-like growth factor-1 and collagen type I.","authors":"Lim, Chae Jin; Jeon, Jung Eun; Jeong, Se Kyoo; Yoon, Seok Jeong; Kwon, Seon Deok; Lim, Jina; Park, Keedon; Kim, Dae Yong; Ahn, Jeong Keun; Kim, Bong-Woo","year":2015,"journal":"BMB reports, 48(9), 501-6","doi":null,"pmid":"25644636","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The GHRP-6-biotin conjugate significantly increased myogenic marker proteins, insulin-like growth factor-1 (IGF-1), and collagen type I expression in cultured myoblasts. It also enhanced metabolic activity, indicated by elevated ATP, lactate levels, and enzymatic activities of lactate dehydrogenase and creatine kinase, suggesting stimulation of muscle cell differentiation and energy metabolism.","whyItMatters":"This research highlights a novel peptide conjugate that may promote muscle growth and function, which is important for developing therapies for muscle wasting or weakness.","specificNumbers":"","methodology":"The study involved treating cultured myoblast cells with the synthesized GHRP-6-biotin conjugate and measuring changes in protein expression, energy metabolites, and enzyme activities. Binding protein analysis was also conducted to identify potential molecular targets.","limitations":"The study was conducted in vitro on cultured cells, so effects in living organisms remain untested. The exact mechanisms and long-term safety are not fully established."},{"rthcId":"RPEP-02717","title":"Ghrelin promotes renal cell carcinoma metastasis via Snail activation and is associated with poor prognosis.","authors":"Lin, Tsung-Chieh; Liu, Yu-Peng; Chan, Yung-Chieh; Su, Chia-Yi; Lin, Yuan-Feng; Hsu, Shih-Lan; Yang, Chung-Shi; Hsiao, Michael","year":2015,"journal":"The Journal of pathology, 237(1), 50-61","doi":"10.1002/path.4552","pmid":"25925728","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Ghrelin is highly expressed in renal cell carcinoma (RCC), particularly metastatic tumors, and promotes RCC cell migration and metastasis via activation of Snail through the GHS-R-PI3K-Akt signaling pathway. Knockdown of ghrelin reduced migration and metastasis, while inhibition of PI3K/Akt signaling blocked ghrelin-induced Snail activation and cell migration.","whyItMatters":"Understanding how ghrelin promotes kidney cancer spread reveals potential targets for therapy to prevent metastasis and improve patient outcomes. It also highlights the role of appetite-regulating hormones in cancer progression.","specificNumbers":"","methodology":"The study analyzed ghrelin expression in RCC tumors and cell lines, used in vitro migration assays with RCC cell lines (786-0, ACHN, A-498), performed ghrelin knockdown experiments, and evaluated in vivo metastasis. Microarray data from TCGA and pathway analyses (IPA and MetaCore) identified Snail regulation. Pharmacological inhibitors and siRNA were used to dissect signaling pathways.","limitations":"The study does not specify patient sample size or clinical trial data, and the evidence strength is unclear. The exact in vivo relevance in humans requires further validation."},{"rthcId":"RPEP-02718","title":"Substance P and Chronic Pain in Patients with Chronic Inflammation of Connective Tissue.","authors":"Lisowska, Barbara; Lisowski, Aleksander; Siewruk, Katarzyna","year":2015,"journal":"PloS one, 10(10), e0139206","doi":"10.1371/journal.pone.0139206","pmid":"26444559","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Serum substance P concentrations were significantly different between osteoarthritis and rheumatoid arthritis patients and positively correlated with chronic pain intensity in both groups.","whyItMatters":"Understanding the link between substance P and chronic pain could help develop targeted treatments for inflammatory joint diseases, improving pain management.","specificNumbers":"","methodology":"The study enrolled patients diagnosed with osteoarthritis and rheumatoid arthritis and measured their serum substance P levels. Pain intensity was assessed and correlated with substance P concentrations to evaluate their relationship.","limitations":"The study type and evidence strength were not specified, and the sample size and control details are unclear, limiting the ability to generalize findings."},{"rthcId":"RPEP-02719","title":"Collagen and gelatin.","authors":"Liu, Dasong; Nikoo, Mehdi; Boran, Gökhan; Zhou, Peng; Regenstein, Joe M","year":2015,"journal":"Annual review of food science and technology, 6, 527-57","doi":"10.1146/annurev-food-031414-111800","pmid":"25884286","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review synthesizes current understanding across several areas:\n\n- Collagen structure varies with source and season, affecting extraction conditions and applications\n- Fish collagen and gelatin are gaining interest as alternatives to mammalian sources due to safety (BSE/prion concerns) and religious considerations\n- Collagen-derived peptides generated through hydrolysis have demonstrated bioactivities in both in vitro and in vivo models\n- Beyond nutritional value, collagen peptides may exert biological effects on extracellular matrix cells through food-derived peptides after ingestion\n- Applications span food, pharmaceutical, cosmetic, and biomedical industries\n- Novel applications continue to emerge for collagen and gelatin products","whyItMatters":"The collagen supplement market has grown enormously, but scientific understanding of how collagen peptides actually work in the body is still evolving. This review provides the scientific basis for understanding collagen-derived peptide bioactivity — helping consumers and healthcare providers make informed decisions about these popular supplements.","specificNumbers":"","methodology":"Comprehensive narrative review published in Annual Review of Food Science and Technology, synthesizing research on collagen structure (using various modern analytical technologies), bioactivities, biological effects, and applications of collagen, gelatin, and gelatin hydrolysates.","limitations":"As a review, findings depend on the quality of underlying studies. Many bioactivity claims are based on in vitro or animal studies, not human clinical trials. Optimal peptide sizes, doses, and specific mechanisms of action in humans are not definitively established. The diversity of collagen sources and processing methods makes standardization difficult."},{"rthcId":"RPEP-02720","title":"Neuroprotective effects of lixisenatide and liraglutide in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease.","authors":"Liu, W; Jalewa, J; Sharma, M; Li, G; Li, L; Hölscher, C","year":2015,"journal":"Neuroscience, 303, 42-50","doi":"10.1016/j.neuroscience.2015.06.054","pmid":"26141845","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In the MPTP mouse model of Parkinson's disease, 14 days of daily liraglutide (25 nmol/kg) and lixisenatide (10 nmol/kg) treatment prevented:\n- Motor impairment on Rotarod, open-field locomotion, and catalepsy tests\n- Reduction of tyrosine hydroxylase (TH) levels — the enzyme needed for dopamine production — in the substantia nigra and basal ganglia\n- Pro-apoptotic signaling (reduced BAX, increased Bcl-2)\n\nExendin-4 at 10 nmol/kg showed no protective effects, suggesting the newer, longer-acting GLP-1 drugs have superior neuroprotective properties at comparable doses.","whyItMatters":"Parkinson's disease has no neuroprotective treatment — current drugs only manage symptoms. GLP-1 drugs are already FDA-approved, well-tolerated, and prescribed to millions for diabetes and weight loss. If they also protect dopamine neurons, they could be repurposed relatively quickly for Parkinson's. This study, combined with a separate pilot clinical trial of exendin-4 in Parkinson's patients showing positive results, built the case for larger human trials that are now underway.","specificNumbers":"","methodology":"C57BL/6 mice received daily injections of the neurotoxin MPTP (20 mg/kg, intraperitoneally) for 7 days to induce Parkinson's-like dopamine neuron loss. Three GLP-1 drugs were tested with daily intraperitoneal injections for 14 days: exendin-4 (10 nmol/kg), liraglutide (25 nmol/kg), and lixisenatide (10 nmol/kg). Motor function was assessed via Rotarod, open-field locomotion, and catalepsy tests. Brain tissue was analyzed for tyrosine hydroxylase levels and apoptotic signaling molecules (BAX and Bcl-2).","limitations":"The MPTP model is a chemical lesion model that only partially replicates human Parkinson's disease — it doesn't produce Lewy bodies or progressive neurodegeneration. The study used a single dose of each drug, so the exendin-4 failure may reflect dose selection rather than true inferiority. The 14-day treatment and short observation period don't address long-term neuroprotection. Sample sizes per group are not specified in the abstract. Intraperitoneal injection is not the clinical route for these drugs."},{"rthcId":"RPEP-02721","title":"Bioprinting synthetic self-assembling peptide hydrogels for biomedical applications.","authors":"Loo, Yihua; Hauser, Charlotte A E","year":2015,"journal":"Biomedical materials (Bristol, England), 11(1), 014103","doi":"10.1088/1748-6041/11/1/014103","pmid":"26694103","tags":[],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Short synthetic self-assembling peptides are ideal bioinks for 3D bioprinting because they naturally form nanofibrous hydrogels that mimic the extracellular matrix — the scaffold that surrounds cells in living tissue. These peptide gels keep cells alive, maintain their normal function, and respond to stimuli (temperature, pH) to gel on demand.\n\nKey advantages for bioprinting: tunable mechanical strength (can be adjusted for different tissue types), excellent shape retention after printing, biocompatibility for implantation, biodegradability, and easy chemical customization. Their short length makes them simple and cheap to synthesize compared to protein-based bioinks.","whyItMatters":"3D bioprinting promises to revolutionize medicine — from printing replacement organs to creating tumor models for drug testing. But the technology has been held back by one problem: there aren’t enough good bioinks. Self-assembling peptide hydrogels solve many of the requirements simultaneously: they’re biocompatible, printable, tunable, and can be customized with cell-binding or drug-releasing functions. This review makes the case that peptide-based bioinks could be the key material that unlocks practical bioprinting.","specificNumbers":"Short synthetic peptides (typically 2–20 amino acids) · nanofibrous hydrogel formation · stimuli-responsive gelation · tunable mechanical properties · biocompatible and biodegradable · customizable via functionalization","methodology":"Review article examining multiple classes of synthetic self-assembling peptides and their suitability as bioinks for 3D bioprinting. Covers peptide design principles, self-assembly mechanisms, gelation behavior, mechanical properties, biocompatibility, and applications in tissue engineering and drug delivery.","limitations":"Review article with no new experimental data. Most peptide bioink studies described were at the proof-of-concept stage. Long-term in vivo performance, immune responses to implanted peptide scaffolds, and scalability of bioprinting with peptide inks remain open questions. Published in 2015 — the field has advanced significantly since."},{"rthcId":"RPEP-02722","title":"Peptide Bioink: Self-Assembling Nanofibrous Scaffolds for Three-Dimensional Organotypic Cultures.","authors":"Loo, Yihua; Lakshmanan, Anupama; Ni, Ming; Toh, Lai Ling; Wang, Shi; Hauser, Charlotte A E","year":2015,"journal":"Nano letters, 15(10), 6919-25","doi":"10.1021/acs.nanolett.5b02859","pmid":"26214046","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Lysine-containing hexapeptides self-assemble into nanofibrous hydrogels with stiffness up to 40 kPa, supporting 3D culture and differentiation of human stem cells into organotypic gastrointestinal and skin tissues.","whyItMatters":"Developing peptide bioinks with high stiffness and biocompatibility advances 3D tissue engineering, enabling more realistic organ models for research and medical applications.","specificNumbers":"","methodology":"The study synthesized lysine-containing hexapeptides that self-assemble into nanofibrous hydrogels. These peptide bioinks were tested for mechanical properties and used to culture human stem cells and primary cells, assessing their viability and differentiation into organ-like structures.","limitations":"The study does not specify long-term stability or in vivo performance of the bioinks, and the evidence strength and study type were not detailed."},{"rthcId":"RPEP-02723","title":"New Prognostic Biomarkers in Patients With Traumatic Brain Injury.","authors":"Lorente, Leonardo","year":2015,"journal":"Archives of trauma research, 4(4), e30165","doi":"10.5812/atr.30165","pmid":"26848476","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Five circulating biomarkers — substance P (a neuropeptide), soluble CD40 ligand, TIMP-1, malondialdehyde, and fragmented cytokeratin-18 — have been identified as prognostic indicators of mortality in traumatic brain injury patients. Each biomarker reflects a different pathway of secondary brain injury: substance P indicates neuroinflammation, sCD40L reflects coagulation and inflammation, TIMP-1 relates to neuroinflammatory matrix remodeling, MDA marks oxidative damage, and CK-18 fragmented signals apoptotic cell death.\n\nSubstance P, a tachykinin family neuropeptide synthesized in the central and peripheral nervous system, exerts proinflammatory effects through binding to neurokinin-1 receptors, making it a particularly relevant peptide biomarker in brain injury.","whyItMatters":"Traumatic brain injury is a leading cause of death and disability, and much of the damage occurs in the hours and days after impact through secondary injury pathways. Blood-based biomarkers that predict which patients are at highest risk of dying could help clinicians make faster, more targeted treatment decisions and may point toward new therapeutic targets.","specificNumbers":"5 novel biomarkers · 4 pathways (inflammation, coagulation, oxidation, apoptosis)","methodology":"This is a narrative review summarizing recent studies that identified circulating blood biomarkers associated with mortality in traumatic brain injury patients. The review covers biomarkers across four key secondary injury pathways.","limitations":"As a narrative review, this paper does not present new experimental data or perform a systematic analysis of the evidence. The specific study designs, sample sizes, and statistical strength behind each biomarker association are not detailed in the abstract. The clinical utility of these biomarkers in routine practice remains to be validated."},{"rthcId":"RPEP-02724","title":"\"Potential health benefits of lunasin: a multifaceted soy-derived bioactive peptide\".","authors":"Lule, Vaibhao Kisanrao; Garg, Sheenam; Pophaly, Sarang Dilip; Hitesh; Tomar, Sudhir Kumar","year":2015,"journal":"Journal of food science, 80(3), R485-94","doi":"10.1111/1750-3841.12786","pmid":"25627564","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02725","title":"Constitutive and ghrelin-dependent GHSR1a activation impairs CaV2.1 and CaV2.2 currents in hypothalamic neurons.","authors":"López Soto, Eduardo Javier; Agosti, Francina; Cabral, Agustina; Mustafa, Emilio Roman; Damonte, Valentina Martínez; Gandini, Maria Alejandra; Rodríguez, Silvia; Castrogiovanni, Daniel; Felix, Ricardo; Perelló, Mario; Raingo, Jesica","year":2015,"journal":"The Journal of general physiology, 146(3), 205-19","doi":"10.1085/jgp.201511383","pmid":"26283199","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Constitutive and ghrelin-dependent activation of GHSR1a significantly impairs CaV2.1 and CaV2.2 calcium channel currents in hypothalamic neurons via distinct Gi/o and Gq protein pathways, respectively, leading to reduced GABA release.","whyItMatters":"Understanding how GHSR1a modulates calcium channels and neurotransmitter release helps clarify its role in brain signaling and could inform therapeutic strategies targeting metabolic and neurological disorders involving ghrelin signaling.","specificNumbers":"","methodology":"The study used rat and mouse hypothalamic neurons and a heterologous expression system to measure calcium channel currents under conditions of constitutive and ghrelin-stimulated GHSR1a activation. Electrophysiological recordings assessed channel activity and neurotransmitter release.","limitations":"The study does not specify the in vivo physiological consequences of these findings, and the evidence strength and study type were not clearly defined, limiting direct clinical translation."},{"rthcId":"RPEP-02726","title":"Agonism, Antagonism, and Inverse Agonism Bias at the Ghrelin Receptor Signaling.","authors":"M'Kadmi, Céline; Leyris, Jean-Philippe; Onfroy, Lauriane; Galés, Céline; Saulière, Aude; Gagne, Didier; Damian, Marjorie; Mary, Sophie; Maingot, Mathieu; Denoyelle, Séverine; Verdié, Pascal; Fehrentz, Jean-Alain; Martinez, Jean; Banères, Jean-Louis; Marie, Jacky","year":2015,"journal":"The Journal of biological chemistry, 290(45), 27021-27039","doi":"10.1074/jbc.M115.659250","pmid":"26363071","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The study demonstrated that GHS-R1a receptor ligands show signaling bias by selectively activating or inhibiting specific G protein pathways (Gq, Gi/o, G13) and β-arrestin2 recruitment. Notably, some ligands acted as inverse agonists for Gq but not G13, indicating pathway-specific inverse agonism at GHS-R1a.","whyItMatters":"Understanding how to selectively modulate ghrelin receptor signaling pathways enables the development of drugs that target only the desired therapeutic effects, potentially reducing side effects in obesity and addiction treatments.","specificNumbers":"","methodology":"Using HEK293T cells expressing GHS-R1a, the researchers employed bioluminescence resonance energy transfer (BRET)-based biosensors to monitor activation of multiple G protein subtypes and β-arrestin2 recruitment. They tested a panel of synthetic ligands to evaluate their efficacy and signaling bias across different pathways.","limitations":"The study was conducted in vitro using HEK293T cells, which may not fully replicate receptor behavior in living organisms. The exact therapeutic implications require further in vivo validation."},{"rthcId":"RPEP-02727","title":"Protective effects of SS31 on t‑BHP induced oxidative damage in 661W cells.","authors":"Ma, Wei; Zhu, Xiaobo; Ding, Xiaoyan; Li, Tao; Hu, Yijun; Hu, Xuting; Yuan, Lin; Lei, Lei; Hu, Andina; Luo, Yan; Tang, Shibo","year":2015,"journal":"Molecular medicine reports, 12(4), 5026-34","doi":"10.3892/mmr.2015.4055","pmid":"26165373","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"SS31 treatment improved viability of 661W cells exposed to t-BHP-induced oxidative stress, reduced apoptosis in a dose-dependent manner, decreased mitochondrial reactive oxygen species, preserved mitochondrial membrane potential, and prevented cytochrome c release.","whyItMatters":"Understanding how SS31 protects cells from oxidative damage could lead to new treatments for diseases involving mitochondrial dysfunction and oxidative stress, such as eye disorders.","specificNumbers":"","methodology":"661W cells were exposed to oxidative stress using t-BHP and treated with varying concentrations of SS31. Cell viability was measured by MTT assay, apoptosis by flow cytometry and staining, oxidative damage markers by immunofluorescence, and mitochondrial function by confocal microscopy and flow cytometry.","limitations":"The study was conducted in vitro using a cell line, so results may not fully translate to living organisms. The study type and evidence strength were not specified."},{"rthcId":"RPEP-02728","title":"Ghrelin increases growth hormone production and functional expression of NaV1.1 and Na V1.2 channels in pituitary somatotropes.","authors":"Magdaleno-Méndez, Adasue; Domínguez, Belisario; Rodríguez-Andrade, Araceli; Barrientos-Morales, Manuel; Cervantes-Acosta, Patricia; Hernández-Beltrán, Antonio; González-Ramírez, Ricardo; Felix, Ricardo","year":2015,"journal":"Endocrine, 48(3), 929-36","doi":"10.1007/s12020-014-0392-x","pmid":"25151402","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Chronic treatment with ghrelin and its synthetic analog GHRP-6 significantly increases growth hormone release from bovine pituitary somatotropes, associated with an increase in Na+ macroscopic current. This effect is abolished by tetrodotoxin, indicating involvement of TTX-sensitive Na+ channels NaV1.1 and NaV1.2, whose transcript levels are upregulated by ghrelin and GHRP-6.","whyItMatters":"Understanding how ghrelin regulates growth hormone secretion via sodium channels can help develop new treatments for growth disorders and improve knowledge of pituitary cell function.","specificNumbers":"","methodology":"The study used cultured bovine pituitary somatotropes treated chronically with ghrelin and GHRP-6. Growth hormone release was measured alongside electrophysiological recordings of Na+ currents. RT-PCR was performed to assess mRNA levels of GH and sodium channel isoforms. Sodium channel blockade was tested using tetrodotoxin.","limitations":"The study was conducted in cultured bovine cells, which may not fully replicate human physiology. The exact signaling pathways linking ghrelin to sodium channel expression were not detailed."},{"rthcId":"RPEP-02729","title":"Egg ovotransferrin-derived ACE inhibitory peptide IRW increases ACE2 but decreases proinflammatory genes expression in mesenteric artery of spontaneously hypertensive rats.","authors":"Majumder, Kaustav; Liang, Guanxiang; Chen, Yanhong; Guan, LeLuo; Davidge, Sandra T; Wu, Jianping","year":2015,"journal":"Molecular nutrition & food research, 59(9), 1735-44","doi":"10.1002/mnfr.201500050","pmid":"26016560","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02730","title":"Sleeve gastrectomy effects on hunger, satiation, and gastrointestinal hormone and motility responses after a liquid meal test.","authors":"Mans, Esther; Serra-Prat, Mateu; Palomera, Elisabet; Suñol, Xavier; Clavé, Pere","year":2015,"journal":"The American journal of clinical nutrition, 102(3), 540-7","doi":"10.3945/ajcn.114.104307","pmid":"26201818","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Sleeve gastrectomy patients showed significantly different gut peptide hormone profiles compared to both morbidly obese and non-obese groups:\n\n- Lowest ghrelin concentrations (the primary hunger-stimulating peptide)\n- Higher early postprandial cholecystokinin (CCK) peaks — a satiety peptide\n- Higher early postprandial glucagon-like peptide 1 (GLP-1) peaks — a satiety and insulin-stimulating peptide\n- Accelerated gastric emptying compared to both control groups\n- Improved insulin resistance pattern compared to morbidly obese patients\n- Reduced hunger and increased satiation scores\n\nInterestingly, no differences in hunger and satiation were observed between morbidly obese and non-obese groups before surgery, suggesting the hormonal changes after surgery drive the appetite effects rather than stomach size alone.","whyItMatters":"This study demonstrates that sleeve gastrectomy works not just by making the stomach smaller, but by fundamentally rewiring the gut's peptide hormone signaling. Understanding these hormonal mechanisms helps explain why bariatric surgery is so much more effective than dieting alone — and connects to why GLP-1 drugs like semaglutide mimic some of these same effects pharmacologically.","specificNumbers":"","methodology":"Case-control study (registered trial NCT02414893) comparing three groups: morbidly obese (n=16), post-sleeve gastrectomy (n=8), and non-obese controls (n=16). After a 10-hour fast, participants consumed a standardized 200 mL liquid meal (400 kcal + 1.5 g paracetamol for gastric emptying measurement). Hunger, satiation, hormone concentrations, and gastric and gallbladder emptying were measured at multiple time points over 4 hours.","limitations":"The sleeve gastrectomy group was small (n=8). The study was cross-sectional, not longitudinal, so pre-surgery baseline data from the same patients was not available. Long-term hormonal changes were not assessed. A single liquid meal may not represent the full range of dietary responses. The exact timing of surgery relative to testing was not specified in the abstract."},{"rthcId":"RPEP-02731","title":"cis-Peptide Bonds: A Key for Intestinal Permeability of Peptides? .","authors":"Marelli, Udaya Kiran; Ovadia, Oded; Frank, Andreas Oliver; Chatterjee, Jayanta; Gilon, Chaim; Hoffman, Amnon; Kessler, Horst","year":2015,"journal":"Chemistry (Weinheim an der Bergstrasse, Germany), 21(43), 15148-52","doi":"10.1002/chem.201501600","pmid":"26337831","tags":[],"studyType":"in vitro","evidenceStrength":"low","keyFinding":"N-methylated cis-peptide bonds appear to be a key structural feature that enables cyclic peptides to cross the intestinal barrier. Among 13 N-methylated cyclic pentaalanine peptides tested, those containing cis-peptide bonds showed the highest intestinal permeability in Caco-2 cell models. This structural feature is shared by known orally available cyclic peptides like cyclosporine A. The study also found that enantiomeric pairs (mirror-image peptides) had different permeabilities, strongly suggesting that absorption involves specific carrier-mediated transport pathways rather than simple passive diffusion, especially for polar peptide scaffolds.","whyItMatters":"The biggest obstacle to oral peptide drugs is their inability to cross the intestinal wall — they get degraded by digestive enzymes and can't penetrate the gut lining. Identifying specific structural features (like cis-peptide bonds) that enable gut absorption is critical for designing the next generation of oral peptide therapeutics. If medicinal chemists can incorporate these features into therapeutic peptides, it could transform peptide drugs from injection-only medications into pills — dramatically improving patient compliance and accessibility.","specificNumbers":"13 cyclic pentapeptides tested · Caco-2 and PAMPA permeability assays · cis-peptide bond identified as key feature · Enantiomeric differential permeability observed","methodology":"Researchers synthesized 13 N-methylated cyclic pentaalanine peptides derived from the cyclo(-D-Ala-Ala4-) template. Intestinal permeability was measured using Caco-2 cell monolayers (a standard model for intestinal epithelium) and PAMPA (parallel artificial membrane permeability assay). Structural conformations were characterized to correlate backbone geometry with permeability. Enantiomeric pairs were compared to distinguish passive transport from carrier-mediated uptake.","limitations":"This is an in vitro study using cell models — actual in vivo oral bioavailability may differ due to additional factors like enzymatic degradation, bile salt interactions, and first-pass liver metabolism. Only 13 peptides from a single template were tested, limiting the generalizability of the structural rules. The peptides had generally moderate to low permeability, with only a few reaching the paracellular marker level. The mechanistic basis for how cis-peptide bonds promote permeability remains hypothetical."},{"rthcId":"RPEP-02732","title":"Enantiomeric cyclic peptides with different Caco-2 permeability suggest carrier-mediated transport.","authors":"Marelli, Udaya Kiran; Bezençon, Jacqueline; Puig, Eduard; Ernst, Beat; Kessler, Horst","year":2015,"journal":"Chemistry (Weinheim an der Bergstrasse, Germany), 21(22), 8023-7","doi":"10.1002/chem.201501270","pmid":"25917866","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The researchers tested enantiomeric pairs of five cyclic hexapeptides (three polar, two lipophilic) using two permeability assays. In the PAMPA assay (which measures only passive diffusion through an artificial membrane), all enantiomeric pairs showed identical permeability, as expected for mirror-image molecules with the same physical properties.\n\nHowever, in the Caco-2 cell model (which contains biological transport machinery), the polar enantiomeric peptides showed significantly different permeability in both apical-to-basolateral and basolateral-to-apical directions. One lipophilic pair also showed differences, while the second lipophilic pair showed equivalent permeability. This discrepancy between PAMPA and Caco-2 results provides the first evidence that carrier-mediated transporters contribute to intestinal peptide absorption, particularly for polar peptides.","whyItMatters":"The inability to deliver peptide drugs orally is one of the biggest barriers in peptide therapeutics — most must be injected, limiting patient convenience and compliance. This study's demonstration that the intestine has active transport mechanisms for cyclic peptides opens a new strategy: instead of solely engineering peptides for passive membrane permeation (making them more fat-soluble), researchers could design peptides that harness the gut's own transport proteins to cross the intestinal wall. This could fundamentally change how oral peptide drugs are designed.","specificNumbers":"","methodology":"The study synthesized enantiomeric pairs of five N-methylated cyclic hexapeptides — three with polar character and two lipophilic. Lipophilicity was measured as logD at pH 7.4. Passive permeability was assessed using the parallel artificial membrane permeability assay (PAMPA), which uses a synthetic lipid membrane without biological components. Cellular permeability was measured using Caco-2 cell monolayers (a standard model of intestinal epithelium containing active transporters) in both directions across the cell layer.","limitations":"The study used in vitro models (Caco-2 cells) that, while standard, may not fully recapitulate in vivo intestinal complexity including mucus layers, gut microbiome, and regional variations in transporter expression. The specific carrier proteins responsible for the differential transport were not identified. The number of peptide pairs tested was limited to five, so the generalizability of the finding to other peptide structures is uncertain. No in vivo absorption data was presented."},{"rthcId":"RPEP-02733","title":"Mistic's membrane association and its assistance in overexpression of a human GPCR are independent processes.","authors":"Marino, Jacopo; Bordag, Natalie; Keller, Sandro; Zerbe, Oliver","year":2015,"journal":"Protein science : a publication of the Protein Society, 24(1), 38-48","doi":"10.1002/pro.2582","pmid":"25297828","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The third helical segment of Mistic interacts only with LDAO micelles and does not integrate into lipid bilayers, while the other helices do interact with membranes. Despite these differences, all helical fragments can substitute full-length Mistic to promote overexpression of a human GPCR in E. coli, indicating that membrane association and overexpression assistance are independent processes.","whyItMatters":"Understanding how Mistic aids membrane protein production without needing membrane binding can improve strategies for producing challenging proteins like human GPCRs in bacterial systems, which is valuable for research and drug development.","specificNumbers":"","methodology":"The study used GFP-fused Mistic helical fragments expressed in E. coli to study cellular localization, and synthesized peptides analyzed by circular dichroism spectroscopy to assess membrane interaction. Bioinformatic analysis expanded the known Mistic homologs and identified conserved genetic elements related to protein translation.","limitations":"The study did not specify the exact mechanisms by which Mistic fragments enhance protein expression, and the evidence strength and study type were not clearly defined."},{"rthcId":"RPEP-02734","title":"Perforating corneal injury in rat and pentadecapeptide BPC 157.","authors":"Masnec, Sanja; Kokot, Antonio; Zlatar, Mirna; Kalauz, Miro; Kunjko, Kristian; Radic, Bozo; Klicek, Robert; Drmic, Domagoj; Lazic, Ratimir; Brcic, Luka; Radic, Radivoje; Ivekovic, Renata; Seiwerth, Sven; Sikiric, Predrag","year":2015,"journal":"Experimental eye research, 136, 9-15","doi":"10.1016/j.exer.2015.04.016","pmid":"25912999","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BPC 157 administered as eye drops at doses of 2 μg/mL and 2 ng/mL accelerated corneal wound healing in rats, with complete epithelial closure by 72 hours (2 μg) and 96 hours (2 ng). The treatment also prevented neovascularization in the injury site, promoting rapid restoration of corneal transparency.","whyItMatters":"This study suggests BPC 157 could be a promising therapeutic agent for enhancing corneal wound healing and maintaining transparency, which is crucial for vision. It offers potential for developing treatments for corneal injuries and ulcers.","specificNumbers":"","methodology":"A 2-mm penetrating corneal incision was made in rat eyes, followed by topical application of BPC 157 eye drops at three concentrations every 8 hours for 120 hours. Healing progress was assessed using fluorescein and Seidel tests, and observations of epithelial defects, aqueous cells, and neovascularization were recorded.","limitations":"The study was conducted in rats, so results may not directly translate to humans. The study type and evidence strength were not specified, limiting assessment of robustness."},{"rthcId":"RPEP-02735","title":"Ligation of synthetic peptides to proteins using semisynthetic protein trans-splicing.","authors":"Matern, Julian C J; Bachmann, Anne-Lena; Thiel, Ilka V; Volkmann, Gerrit; Wasmuth, Alexandra; Binschik, Jens; Mootz, Henning D","year":2015,"journal":"Methods in molecular biology (Clifton, N.J.), 1266, 129-43","doi":"10.1007/978-1-4939-2272-7_9","pmid":"25560072","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The study demonstrates that the M86 mutant of the Ssp DnaB intein and the MX1 mutant of the AceL-TerL intein, both with very short N-terminal intein fragments, enable efficient N-terminal labeling of proteins via semisynthetic protein trans-splicing.","whyItMatters":"This method offers a powerful tool for peptide researchers to modify proteins precisely and efficiently, facilitating studies of protein function and the development of protein-based therapeutics.","specificNumbers":"","methodology":"The authors provide detailed protocols using two engineered split intein systems with short N-terminal fragments accessible by solid-phase peptide synthesis to achieve protein labeling through semisynthetic protein trans-splicing under mild conditions.","limitations":"The study focuses on specific engineered inteins and may require optimization for other proteins or intein systems; the overall evidence strength and study type are not specified."},{"rthcId":"RPEP-02736","title":"Promotion of Wakefulness and Energy Expenditure by Orexin-A in the Ventrolateral Preoptic Area.","authors":"Mavanji, Vijayakumar; Perez-Leighton, Claudio E; Kotz, Catherine M; Billington, Charles J; Parthasarathy, Sairam; Sinton, Christopher M; Teske, Jennifer A","year":2015,"journal":"Sleep, 38(9), 1361-70","doi":"10.5665/sleep.4970","pmid":"25845696","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02737","title":"Plasma membrane poration by opioid neuropeptides: a possible mechanism of pathological signal transduction.","authors":"Maximyuk, O; Khmyz, V; Lindskog, C-J; Vukojević, V; Ivanova, T; Bazov, I; Hauser, K F; Bakalkin, G; Krishtal, O","year":2015,"journal":"Cell death & disease, 6(3), e1683","doi":"10.1038/cddis.2015.39","pmid":"25766322","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Using fluorescence correlation spectroscopy and patch-clamp electrophysiology, the researchers demonstrated that dynorphins accumulate in the plasma membrane and induce transient increases in ionic conductance consistent with the formation of giant (~2.7 nm diameter) unstructured, non-ion-selective membrane pores.\n\nCritically, the potency of different dynorphin variants to porate membranes correlated with their known pathogenic effects in cellular and animal models of neurodegeneration. This establishes membrane poration as a probable mechanism for dynorphin-mediated pathological signal transduction, neuronal excitation, and cell death.","whyItMatters":"Dynorphin levels are elevated in many neurological conditions including traumatic brain injury, epilepsy, and neurodegenerative diseases. Understanding that these peptides can directly damage cells by porating their membranes — bypassing traditional receptor pathways — opens an entirely new target for therapeutic intervention in these devastating conditions.","specificNumbers":"","methodology":"The study used two complementary biophysical techniques: fluorescence correlation spectroscopy to track dynorphin accumulation in the plasma membrane, and patch-clamp electrophysiology to measure changes in ionic conductance (electrical current across the membrane) when dynorphins were applied. Multiple dynorphin variants and other opioid peptides were compared to establish structure-activity relationships for membrane poration.","limitations":"The study was conducted primarily in cultured cells and model systems, not in living organisms. The exact in vivo relevance of membrane poration at physiological dynorphin concentrations is not established. The long-term consequences of repeated membrane poration events were not examined. The 2.7 nm pore diameter is an estimate based on conductance measurements."},{"rthcId":"RPEP-02738","title":"Chemical synthesis of a pore-forming antimicrobial protein, caenopore-5, by using native chemical ligation at a glu-cys site.","authors":"Medini, Karima; Harris, Paul W R; Hards, Kiel; Dingley, Andrew J; Cook, Gregory M; Brimble, Margaret A","year":2015,"journal":"Chembiochem : a European journal of chemical biology, 16(2), 328-36","doi":"10.1002/cbic.201402513","pmid":"25425108","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Caenopore-5, an 82-amino acid pore-forming antimicrobial protein, was chemically synthesized using Boc solid-phase peptide synthesis combined with native chemical ligation at a Glu-Cys junction. The synthetic protein folded properly as confirmed by NMR and circular dichroism, and exhibited membrane permeabilization activity comparable to recombinant protein, with no γ-linked by-products detected.","whyItMatters":"This work demonstrates a reliable chemical method to produce antimicrobial peptides like caenopore-5, which are promising alternatives to traditional antibiotics amid rising antibiotic resistance. Synthetic production allows detailed study and potential modification of these peptides for therapeutic use.","specificNumbers":"","methodology":"The study employed Boc solid-phase peptide synthesis to produce peptide fragments, which were then joined via native chemical ligation at a glutamic acid-cysteine site. Protein folding was verified using (1)H NMR spectroscopy and circular dichroism, and functional activity was assessed by measuring membrane permeabilization of the synthetic protein and its analogues.","limitations":"The study did not specify the detailed biological activity spectrum or in vivo efficacy of the synthetic protein. The exact study type and evidence strength were not provided, limiting assessment of clinical relevance."},{"rthcId":"RPEP-02739","title":"Incretin-based therapies: where will we be 50 years from now?","authors":"Meier, Juris J; Nauck, Michael A","year":2015,"journal":"Diabetologia, 58(8), 1745-50","doi":"10.1007/s00125-015-3608-6","pmid":"25994073","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Incretin-based therapies have significantly advanced type 2 diabetes management and are expected to expand through longer-acting formulations, novel delivery methods, combination hormone therapies, and applications to other diseases.","whyItMatters":"Understanding the future directions of incretin-based therapies helps guide research and clinical strategies to improve treatment options for diabetes and related conditions.","specificNumbers":"","methodology":"This article is a commentary providing expert opinions and future perspectives on incretin-based therapies rather than a primary research study.","limitations":"As a commentary, the article does not present new experimental data and the evidence strength and study type are not specified."},{"rthcId":"RPEP-02740","title":"Involvement of Endogenous Enkephalins and β-Endorphin in Feeding and Diet-Induced Obesity.","authors":"Mendez, Ian A; Ostlund, Sean B; Maidment, Nigel T; Murphy, Niall P","year":2015,"journal":"Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 40(9), 2103-12","doi":"10.1038/npp.2015.67","pmid":"25754760","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Proenkephalin knockout (PENK KO) mice showed reduced feeding motivation — fewer licking bouts for sucrose but normal bout lengths — and had lower baseline body weight on regular chow and attenuated weight gain on an energy-dense cafeteria diet.\n\nβ-endorphin-deficient (BEND KO) mice showed altered taste reward — shorter licking bouts (suggesting reduced palatability) but normal bout frequency. Critically, BEND KO mice were insensitive to shifts in sucrose concentration and hunger state, indicating β-endorphin specifically mediates orosensory reward responses under conditions of high need or high stimulus value.\n\nPENK KO but not BEND KO mice showed resistance to diet-induced obesity, demonstrating that enkephalins — not β-endorphin — are the primary opioid peptides regulating body weight through motivational tone.","whyItMatters":"Obesity is a global epidemic, and the opioid system in the brain has long been a target for appetite-suppressing drugs. But drugs that broadly block mu-opioid receptors (like naltrexone) have shown limited long-term efficacy for weight control. This study explains why: enkephalins and β-endorphin have fundamentally different roles in eating behavior, and blocking both simultaneously may counterproductively disrupt the system. More targeted approaches — specifically addressing enkephalin-mediated motivation — might be more effective for obesity treatment.","specificNumbers":"","methodology":"The study used proenkephalin knockout (PENK KO) and β-endorphin-deficient (BEND KO) mice compared to wild-type controls. Palatable liquid consumption was measured using detailed lickometer analysis (bout frequency and bout length) with sucrose solutions at varying concentrations. Body weight was tracked during consumption of standard chow and an energy-dense 'cafeteria diet.' Sensitivity to sucrose concentration shifts and hunger states was assessed to distinguish motivational from hedonic components of feeding.","limitations":"The study was conducted in genetically modified mice, and compensatory developmental changes in knockout animals may confuse interpretation. Human opioid system regulation of feeding may differ. The cafeteria diet model, while useful, doesn't fully replicate human eating patterns. The study focused on sucrose consumption as a measure of palatability, which may not generalize to all food types. Specific neural circuits mediating these peptide effects were not identified."},{"rthcId":"RPEP-02741","title":"Intranasal Delivery of Proteins and Peptides in the Treatment of Neurodegenerative Diseases.","authors":"Meredith, M Elizabeth; Salameh, Therese S; Banks, William A","year":2015,"journal":"The AAPS journal, 17(4), 780-7","doi":"10.1208/s12248-015-9719-7","pmid":"25801717","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02742","title":"Cyclotides: a natural combinatorial peptide library or a bioactive sequence player?","authors":"Mollica, Adriano; Costante, Roberto; Stefanucci, Azzurra; Novellino, Ettore","year":2015,"journal":"Journal of enzyme inhibition and medicinal chemistry, 30(4), 575-80","doi":"10.3109/14756366.2014.954108","pmid":"25244541","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Cyclotides have emerged as powerful tools in drug discovery through two principal approaches: (1) as scaffolds in which bioactive peptides can be grafted to improve stability, oral bioactivity, and binding to G-protein coupled receptors (GPCRs), and (2) as natural combinatorial peptide libraries for screening. Their unique circular structure with a cystine knot makes them exceptionally stable compared to linear peptides.","whyItMatters":"One of the biggest problems in peptide drug development is that peptides break down quickly in the body and can't usually be taken by mouth. Cyclotides — naturally circular, ultra-stable peptides from plants — offer a solution: you can insert therapeutic peptide sequences into their framework and they survive digestion, opening the door to oral peptide drugs.","specificNumbers":"","methodology":"This is a perspective review examining the current state of cyclotide research in drug discovery. The authors surveyed published work on two main applications: using cyclotides as scaffolds to stabilize bioactive peptides, and using them as natural peptide libraries for identifying new drug candidates.","limitations":"As a brief perspective review, this paper does not present original experimental data. It provides a high-level overview rather than a systematic analysis of the literature. Specific clinical applications of cyclotide scaffolds remain theoretical at the time of writing."},{"rthcId":"RPEP-02743","title":"Antimicrobial Peptide Lactoferricin B-Induced Rapid Leakage of Internal Contents from Single Giant Unilamellar Vesicles.","authors":"Moniruzzaman, Md; Alam, Jahangir Md; Dohra, Hideo; Yamazaki, Masahito","year":2015,"journal":"Biochemistry, 54(38), 5802-14","doi":"10.1021/acs.biochem.5b00594","pmid":"26368853","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Lactoferricin B induces rapid local ruptures in lipid membranes, causing leakage of internal contents without prior formation of smaller pores. The rate of pore formation increases with stronger electrostatic interactions between the peptide and membrane surface charges. Binding of lactoferricin B also increases the area of the outer membrane layer, contributing to membrane destabilization.","whyItMatters":"Understanding how lactoferricin B disrupts bacterial membranes helps clarify its mechanism as an antimicrobial peptide, which is valuable for designing new antibiotics or peptide-based therapies.","specificNumbers":"","methodology":"The study used fluorescence probes and microscopy to observe lactoferricin B interactions with Escherichia coli and synthetic lipid vesicles, including single giant unilamellar vesicles (GUVs). Leakage rates and membrane shape changes were analyzed statistically to determine the kinetics of pore formation and local rupture.","limitations":"The study was conducted using model membranes and bacterial cells in vitro, which may not fully replicate complex biological environments. The exact molecular details of pore evolution and membrane structural changes remain unresolved due to time resolution limits."},{"rthcId":"RPEP-02744","title":"Evaluation of the Biological Properties and the Enzymatic Stability of Glycosylated Luteinizing Hormone-Releasing Hormone Analogs.","authors":"Moradi, Shayli Varasteh; Varamini, Pegah; Toth, Istvan","year":2015,"journal":"The AAPS journal, 17(5), 1135-43","doi":"10.1208/s12248-015-9769-x","pmid":"25956382","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Glycosylation of LHRH analogs significantly increased their enzymatic stability, with compounds 1 and 6 showing half-lives extended from 3 minutes to up to 103 minutes in kidney membrane enzymes. These glycopeptides also demonstrated significant antiproliferative effects on LHRH receptor-positive prostate cancer cells and stimulated hormone release in rat pituitary cells.","whyItMatters":"Improving the stability of LHRH peptides can enhance their therapeutic potential by prolonging their activity in the body and increasing their effectiveness against hormone-sensitive cancers and hormone regulation.","specificNumbers":"","methodology":"The study involved chemically attaching carbohydrate units (lactose, glucose, galactose) to LHRH peptides and testing their stability against enzymatic degradation in human plasma, rat kidney membranes, and liver homogenates. The antiproliferative activity was assessed on prostate cancer cells, and hormone release was measured in dispersed rat pituitary cells.","limitations":"The study was conducted primarily in vitro and in rat cells, so further in vivo and clinical studies are needed to confirm therapeutic benefits and safety in humans."},{"rthcId":"RPEP-02745","title":"Implications of ghrelin and hexarelin in diabetes and diabetes-associated heart diseases.","authors":"Mosa, Rasha Mofeed Habeeb; Zhang, Zhen; Shao, Renfu; Deng, Chao; Chen, Jiezhong; Chen, Chen","year":2015,"journal":"Endocrine, 49(2), 307-23","doi":"10.1007/s12020-015-0531-z","pmid":"25645463","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Ghrelin and hexarelin exhibit growth hormone-independent cardiovascular activities and protect pancreatic beta cells by enhancing insulin secretion and promoting beta cell regeneration. Hexarelin also regulates PPAR-γ, influencing lipid metabolism and insulin sensitivity, indicating potential therapeutic roles in diabetes and diabetic cardiomyopathy.","whyItMatters":"Understanding how ghrelin and hexarelin affect insulin production and heart function could lead to new treatments for diabetes and its cardiovascular complications.","specificNumbers":"","methodology":"This study is a literature review summarizing findings from multiple experimental studies on ghrelin and hexarelin's physiological roles and therapeutic potential in diabetes and associated heart diseases.","limitations":"The review is based on preclinical and animal studies, with limited direct clinical evidence; the exact mechanisms and efficacy in humans remain to be fully established."},{"rthcId":"RPEP-02746","title":"Dexamethasone decreases substance P expression in human tendon cells: an in vitro study.","authors":"Mousavizadeh, Rouhollah; Backman, Ludvig; McCormack, Robert G; Scott, Alex","year":2015,"journal":"Rheumatology (Oxford, England), 54(2), 318-23","doi":"10.1093/rheumatology/keu315","pmid":"25150176","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Dexamethasone exposure leads to a time-dependent decrease in substance P (SP) mRNA and protein levels in human tendon fibroblasts via glucocorticoid receptor signaling, without affecting the SP receptor NK1R. It also inhibits SP induction by IL-1β and mechanical loading.","whyItMatters":"Understanding that dexamethasone reduces substance P in tendon cells reveals a potential mechanism for its pain-relieving effects in tendinopathy, guiding future therapies targeting SP signaling to treat tendon pain.","specificNumbers":"","methodology":"Human tendon fibroblasts from hamstrings and Achilles tendons were cultured and treated with varying concentrations of dexamethasone and other modulators. Gene expression of SP (TAC1), NK1R, and inflammatory cytokines was measured by quantitative PCR, and SP protein levels were assessed by enzyme immunoassay and western blot.","limitations":"The study was conducted in vitro using isolated human tendon cells, which may not fully replicate the complex environment of tendons in living organisms. The study type and evidence strength were not specified, limiting assessment of clinical applicability."},{"rthcId":"RPEP-02747","title":"Effect of long-term intranasal oxytocin on sexual dysfunction in premenopausal and postmenopausal women: a randomized trial.","authors":"Muin, Dana A; Wolzt, Michael; Marculescu, Rodrig; Sheikh Rezaei, Safoura; Salama, Mohamed; Fuchs, Carola; Luger, Anton; Bragagna, Elia; Litschauer, Brigitte; Bayerle-Eder, Michaela","year":2015,"journal":"Fertility and sterility, 104(3), 715-23.e4","doi":"10.1016/j.fertnstert.2015.06.010","pmid":"26151620","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02748","title":"Ghrelin receptor activity amplifies hippocampal N-methyl-d-aspartate receptor-mediated postsynaptic currents and increases phosphorylation of the GluN1 subunit at Ser896 and Ser897.","authors":"Muniz, Brandon G; Isokawa, Masako","year":2015,"journal":"The European journal of neuroscience, 42(12), 3045-53","doi":"10.1111/ejn.13107","pmid":"26490687","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Activation of the ghrelin receptor (GHSR1a) in hippocampal CA1 pyramidal neurons enhances NMDA receptor-mediated excitatory postsynaptic currents and increases phosphorylation of the GluN1 subunit at Ser896 and Ser897. This effect is abolished in GHSR1a knockout and heterozygous mice, indicating a critical role for GHSR1a in modulating NMDA receptor function.","whyItMatters":"Understanding how ghrelin receptors regulate NMDA receptor function in the hippocampus provides insight into mechanisms underlying learning and memory. This could inform future research on cognitive enhancement and neurological disorders involving glutamatergic signaling.","specificNumbers":"","methodology":"The study used hippocampal slice preparations from wild-type, heterozygous, and GHSR1a knockout mice to measure NMDA receptor-mediated currents and GluN1 phosphorylation. Pharmacological agents including a GHSR1a antagonist and inverse agonist were applied to assess receptor involvement. Localization of GHSR1a was examined using fluorescent ghrelin binding, immunoreactivity, and reporter gene expression.","limitations":"The study was conducted in mouse hippocampal slices, which may not fully represent in vivo conditions. The exact behavioral consequences of these molecular changes were not assessed. The evidence strength and study type were not specified."},{"rthcId":"RPEP-02749","title":"The antiproliferative action of [D-Arg(1), D-Phe(5), D-Trp(7,9), LEU(11)] substance P analogue antagonist against small-cell- and non-small-cell lung cancer cells could be due to the pharmacological profile of its tachykinin receptor antagonist.","authors":"Munoz, M; Recio, S; Rosso, M; Redondo, M; Covenas, R","year":2015,"journal":"Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 66(3), 421-6","doi":null,"pmid":"26084224","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The [D-Arg(1), D-Phe(5), D-Trp(7,9), Leu(11)] substance P analogue exerts antiproliferative effects on human small-cell lung cancer (H-69) and non-small-cell lung cancer (COR-L23) cell lines by acting through the neurokinin-1 (NK-1) receptor, inhibiting tumor cell proliferation and inducing apoptosis.","whyItMatters":"Understanding how substance P analogues block lung cancer cell growth via NK-1 receptors could lead to new targeted therapies for lung cancer, a disease with high mortality.","specificNumbers":"","methodology":"The study used competition binding assays with substance P to demonstrate that the antiproliferative action of the synthetic SP analogue occurs via the NK-1 receptor in cultured human lung cancer cell lines.","limitations":"The study was conducted in vitro on cell lines, so results may not fully translate to clinical outcomes in patients; the exact molecular mechanisms remain to be fully elucidated."},{"rthcId":"RPEP-02750","title":"The substance P/NK-1 receptor system: NK-1 receptor antagonists as anti-cancer drugs.","authors":"Munoz, Miguel; Covenas, Rafael; Esteban, Francisco; Redondo, Maximino","year":2015,"journal":"Journal of biosciences, 40(2), 441-63","doi":null,"pmid":"25963269","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tumor cells overexpress NK-1 receptors, which are critical for their survival and proliferation. NK-1 receptor antagonists induce apoptosis in tumor cells, inhibit angiogenesis, and reduce tumor cell migration, making them promising targeted anti-cancer agents. Aprepitant, an NK-1 receptor antagonist already clinically approved for other uses, could be repurposed as an effective anti-tumor drug.","whyItMatters":"Targeting NK-1 receptors offers a new, potentially more specific approach to cancer treatment that may reduce side effects compared to conventional therapies. Repurposing existing drugs like aprepitant could accelerate development of novel cancer treatments.","specificNumbers":"","methodology":"This is a review article summarizing existing research on the role of substance P, NK-1 receptors, and NK-1 receptor antagonists in cancer biology and treatment potential.","limitations":"As a review, the article does not present new experimental data and the clinical effectiveness of NK-1 receptor antagonists as cancer treatments requires further validation through clinical trials."},{"rthcId":"RPEP-02751","title":"A retrospective, multi-center cohort study evaluating the severity- related effects of cerebrolysin treatment on clinical outcomes in traumatic brain injury.","authors":"Muresanu, Dafin F; Ciurea, Alexandru V; Gorgan, Radu M; Gheorghita, Eva; Florian, Stefan I; Stan, Horatiu; Blaga, Alin; Ianovici, Nicolai; Iencean, Stefan M; Turliuc, Dana; Davidescu, Horia B; Mihalache, Cornel; Brehar, Felix M; Mihaescu, Anca S; Mardare, Dinu C; Anghelescu, Aurelian; Chiparus, Carmen; Lapadat, Magdalena; Pruna, Viorel; Mohan, Dumitru; Costea, Constantin; Costea, Daniel; Palade, Claudiu; Bucur, Narcisa; Figueroa, Jesus; Alvarez, Anton","year":2015,"journal":"CNS & neurological disorders drug targets, 14(5), 587-99","doi":null,"pmid":"25924999","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02752","title":"An overview of peptide and peptoid foldamers in medicinal chemistry.","authors":"Mándity, István M; Fülöp, Ferenc","year":2015,"journal":"Expert opinion on drug discovery, 10(11), 1163-77","doi":"10.1517/17460441.2015.1076790","pmid":"26289578","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02753","title":"The integrated hypothalamic tachykinin-kisspeptin system as a central coordinator for reproduction.","authors":"Navarro, Víctor M; Bosch, Martha A; León, Silvia; Simavli, Serap; True, Cadence; Pinilla, Leonor; Carroll, Rona S; Seminara, Stephanie B; Tena-Sempere, Manuel; Rønnekleiv, Oline K; Kaiser, Ursula B","year":2015,"journal":"Endocrinology, 156(2), 627-37","doi":"10.1210/en.2014-1651","pmid":"25422875","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"All three tachykinin peptides (SP via NK1R, NKA via NK2R, NKB via NK3R) induced gonadotropin release in adult male and ovariectomized estradiol-replaced female mice. This effect was abolished in Kiss1r knockout mice, proving kisspeptin-dependence.\n\nSex-specific differences emerged: the NK2R agonist decreased LH in ovariectomized females without estradiol, while the NK1R agonist increased it — contrasting with the NK2R/NK3R pattern. Receptor mapping showed ~50% of arcuate Kiss1 neurons expressed NK1R and 100% expressed NK3R, while NK2R was absent from all kisspeptin and GnRH neurons. Tac1 (SP/NKA) expression was inhibited by estradiol but did not colocalize with Kiss1 mRNA.","whyItMatters":"Kisspeptin is known as the 'master regulator' of reproduction, and NKB was already recognized as its key co-regulator. This study expands the picture to include all three tachykinin peptides in reproductive control, revealing a more complex and integrated neuropeptide network than previously appreciated. Understanding this system has implications for treating infertility, polycystic ovary syndrome, and developing new contraceptive approaches.","specificNumbers":"","methodology":"The researchers centrally infused specific receptor agonists for NK1R (SP receptor), NK2R (NKA receptor), and NK3R (NKB receptor) in adult male mice, ovariectomized estradiol-replaced females, and ovariectomized females without replacement. Kiss1r knockout mice were used to confirm kisspeptin dependence. Gene expression was analyzed by in situ hybridization and single-cell RT-PCR in microdissected brain regions (arcuate nucleus, AVPV), examining Tac1, Tacr1-3, and Kiss1 expression patterns.","limitations":"This is a mouse study, and the tachykinin-kisspeptin system may function differently in humans. The central infusion of agonists does not replicate physiological peptide release patterns. The absence of NK2R on Kiss1 and GnRH neurons raises questions about how the NK2R agonist effects are mediated, which remains unexplained. Specific doses and concentrations used for central infusion are not detailed in the abstract."},{"rthcId":"RPEP-02754","title":"Diet-induced obesity causes peripheral and central ghrelin resistance by promoting inflammation.","authors":"Naznin, Farhana; Toshinai, Koji; Waise, T M Zaved; NamKoong, Cherl; Md Moin, Abu Saleh; Sakoda, Hideyuki; Nakazato, Masamitsu","year":2015,"journal":"The Journal of endocrinology, 226(1), 81-92","doi":"10.1530/JOE-15-0139","pmid":"26016745","tags":["ghrelin","obesity"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Diet-induced obesity caused complete ghrelin resistance in mice — peripheral ghrelin injections failed to increase food intake, suppress oxygen consumption, activate the vagus nerve, or trigger signaling in the hypothalamus. The mechanism: a high-fat diet reduced ghrelin receptor expression in both the nodose ganglion (vagus nerve relay station) and the hypothalamus.\n\nCritically, this resistance was driven by inflammation. The high-fat diet triggered activation of macrophages and microglia and upregulated inflammatory cytokines in both the nodose ganglion and hypothalamus, blunting ghrelin's ability to signal through the vagal afferent pathway that normally carries hunger signals from gut to brain.","whyItMatters":"Ghrelin is supposed to be the body's \"hunger alarm,\" but this study shows obesity breaks that alarm through inflammation. This is analogous to leptin resistance — where obese individuals have high leptin but their brains stop responding to the \"I'm full\" signal. Understanding that ghrelin resistance and leptin resistance share an inflammatory mechanism helps explain why appetite regulation goes haywire in obesity and could point toward anti-inflammatory interventions.","specificNumbers":"12 weeks of high-fat diet; ghrelin receptor mRNA reduced in nodose ganglion and hypothalamus; macrophage/microglia markers upregulated; inflammatory cytokines elevated; complete loss of ghrelin-induced food intake, vagal nerve activity, ERK2/AMPK phosphorylation, and hypothalamic Fos expression","methodology":"Researchers fed mice a high-fat diet for 12 weeks to induce obesity, then tested multiple aspects of ghrelin signaling. They measured food intake response to subcutaneous ghrelin, oxygen consumption, vagal nerve electrical activity, intracellular signaling markers (ERK2 and AMPK phosphorylation) in the nodose ganglion, and Fos expression (a marker of neuronal activation) in the hypothalamus. They also measured ghrelin receptor mRNA levels and inflammatory markers in the nodose ganglion and hypothalamus.","limitations":"This is a mouse study, and high-fat diet-induced obesity in mice may not perfectly model human obesity. The 12-week timeframe is relatively short. The study doesn't establish whether reducing inflammation can restore ghrelin sensitivity. It does not address whether the findings apply to genetic forms of obesity versus diet-induced obesity."},{"rthcId":"RPEP-02755","title":"Incretin-based therapies.","authors":"Neumiller, Joshua J","year":2015,"journal":"The Medical clinics of North America, 99(1), 107-29","doi":"10.1016/j.mcna.2014.08.013","pmid":"25456646","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Incretin-based therapies — GLP-1 receptor agonists and DPP-4 inhibitors — offer unique advantages for type 2 diabetes management: low hypoglycemia risk, effective postprandial glucose control, and weight reduction (GLP-1 RAs). Short-acting GLP-1 RAs primarily target post-meal glucose spikes, while long-acting formulations provide sustained blood sugar lowering. DPP-4 inhibitors work by preventing the breakdown of natural GLP-1 peptide. Safety considerations include pancreatitis risk, C-cell hyperplasia concerns, renal effects, and GI side effects (especially in older adults).","whyItMatters":"This review captures the incretin therapy landscape at a pivotal time — when GLP-1 drugs and DPP-4 inhibitors were transitioning from novel agents to mainstream diabetes treatments. Understanding both drug classes and their different approaches to harnessing the incretin peptide system (mimicking GLP-1 directly vs. preventing its breakdown) provides essential context for the peptide drug revolution that followed.","specificNumbers":"Two drug classes covered · GLP-1 RAs: short-acting and long-acting · DPP-4 inhibitors: oral · low hypoglycemia risk · weight reduction (GLP-1 RAs) · GI side effects most common · CV outcome studies ongoing at time of publication","methodology":"Clinical review published in Medical Clinics of North America summarizing the pharmacology, clinical efficacy, safety profile, and practical prescribing considerations for incretin-based therapies in type 2 diabetes.","limitations":"Published in 2015, before the major cardiovascular outcome trials were completed. Semaglutide and tirzepatide were not yet available. The review predates the expansion of GLP-1 RAs into obesity, cardiovascular risk reduction, and other indications. Safety concerns discussed (pancreatitis, C-cell tumors) have since been largely resolved by larger studies."},{"rthcId":"RPEP-02756","title":"Thymosin alpha1 enhanced cytotoxicity of iNKT cells against colon cancer via upregulating CD1d expression.","authors":"Ni, Chao; Wu, Pin; Wu, Xianguo; Zhang, Ting; Zhang, Tao; Wang, Zhen; Zhang, Sai; Qiu, Fuming; Huang, Jian","year":2015,"journal":"Cancer letters, 356(2 Pt B), 579-88","doi":"10.1016/j.canlet.2014.10.002","pmid":"25304368","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Thymosin alpha1 enhances the cytotoxicity of invariant NKT cells against colorectal cancer cells by upregulating CD1d expression on these cancer cells via the Erk/MAPK signaling pathway. This upregulation leads to stronger immune cell activation and killing efficiency, especially targeting colon cancer stem cells with higher CD1d levels.","whyItMatters":"Understanding how thymosin alpha1 enhances immune cell activity against colon cancer could lead to improved immunotherapy strategies, potentially offering better treatments for colorectal cancer patients.","specificNumbers":"","methodology":"The study used in vitro cell culture experiments and in vivo models to assess the cytotoxic effects of iNKT cells on colorectal cancer cells with and without thymosin alpha1 treatment. Protein expression levels were measured, and pathway inhibition assays were performed to identify the mechanism.","limitations":"The study type and evidence strength are not clearly defined, and the findings need confirmation in larger clinical trials to establish safety and efficacy in humans."},{"rthcId":"RPEP-02757","title":"Peptide macrocycles featuring a backbone secondary amine: a convenient strategy for the synthesis of lipidated cyclic and bicyclic peptides on solid support.","authors":"Oddo, Alberto; Münzker, Lena; Hansen, Paul R","year":2015,"journal":"Organic letters, 17(10), 2502-5","doi":"10.1021/acs.orglett.5b01026","pmid":"25923311","tags":[],"studyType":"methodology","evidenceStrength":"preliminary","keyFinding":"Researchers developed a new way to build ring-shaped (macrocyclic) peptides directly on solid-phase synthesis supports. The key innovation is that the ring closure creates a secondary amine in the peptide backbone that remains chemically reactive — meaning you can keep building on the peptide after cyclization. This enabled the synthesis of both cyclic and bicyclic peptides ranging from 3 to 13 amino acids, and the method was demonstrated by making lipidated antimicrobial peptide variants.","whyItMatters":"Cyclic peptides are more drug-like than linear ones — they're more stable, more selective, and better at crossing cell membranes. But making them is hard, especially when you want to add lipid chains (lipidation) that further improve drug properties. This method solves that problem by leaving a reactive handle inside the ring that allows further chemistry. It could accelerate the development of next-generation antimicrobial peptides and other cyclic peptide drugs.","specificNumbers":"3- to 13-mer macrocycles · compatible with standard Fmoc/tBu SPPS · cyclic and bicyclic peptides produced · lipidated antimicrobial peptide variants demonstrated","methodology":"Organic chemistry method development. The researchers used intramolecular halide substitution by a diamino acid during standard solid-phase peptide synthesis (Fmoc/tBu SPPS) to form macrocyclic peptides. The resulting endocyclic secondary amine was then acylated to continue synthesis, producing lipidated cyclic and bicyclic antimicrobial peptides.","limitations":"This is a synthesis methodology paper — no biological activity data is presented for the antimicrobial peptides produced. The approach was demonstrated on a limited range of peptide sizes. Scalability and compatibility with all amino acid sequences were not fully explored."},{"rthcId":"RPEP-02758","title":"The tetrapeptide N-acetyl-Pro-Pro-Tyr-Leu in skin care formulations-Physicochemical and release studies.","authors":"Olejnik, Anna; Schroeder, Grzegorz; Nowak, Izabela","year":2015,"journal":"International journal of pharmaceutics, 492(1-2), 161-8","doi":"10.1016/j.ijpharm.2015.06.050","pmid":"26188319","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The release rate of the tetrapeptide N-acetyl-Pro-Pro-Tyr-Leu is strongly influenced by the physicochemical properties of the skin care formulation, with higher viscosity semisolids exhibiting slower peptide permeation through membranes.","whyItMatters":"Understanding how formulation properties affect peptide release helps optimize skin care products for better delivery and effectiveness of active peptides.","specificNumbers":"","methodology":"The study prepared different skin care formulations containing the tetrapeptide, characterized their pH, viscosity, stability, and particle size, and calculated peptide diffusion parameters using the Einstein-Smoluchowski equation. Release kinetics were investigated through membrane penetration studies to determine release rate constants.","limitations":"The study did not specify in vivo skin penetration or clinical efficacy, and the exact study type and evidence strength were not provided."},{"rthcId":"RPEP-02759","title":"Evaluation and synthesis of polar aryl- and heteroaryl spiroazetidine-piperidine acetamides as ghrelin inverse agonists.","authors":"Orr, Suvi T M; Beveridge, Ramsay; Bhattacharya, Samit K; Cameron, Kimberly O; Coffey, Steven; Fernando, Dilinie; Hepworth, David; Jackson, Margaret V; Khot, Vishal; Kosa, Rachel; Lapham, Kimberly; Loria, Paula M; McClure, Kim F; Patel, Jigna; Rose, Colin; Saenz, James; Stock, Ingrid A; Storer, Gregory; von Volkenburg, Maria; Vrieze, Derek; Wang, Guoqiang; Xiao, Jun; Zhang, Yingxin","year":2015,"journal":"ACS medicinal chemistry letters, 6(2), 156-61","doi":"10.1021/ml500414n","pmid":"25699143","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Polar heteroaromatic acetic acids and their piperidine amides were synthesized and identified as inverse agonists of the GHS-R1a receptor. Compounds containing ortho-carboxamide groups demonstrated optimal pharmacologic activity, improved physicochemical properties, and enhanced safety profiles. Additionally, the series showed pH-dependent chemical stability.","whyItMatters":"Developing ghrelin receptor inverse agonists with improved safety and pharmacokinetic profiles is important for potential treatments targeting appetite control and metabolic disorders. Enhancing polarity in these compounds may lead to better drug candidates.","specificNumbers":"","methodology":"The study involved chemical synthesis of various polar heteroaromatic acetic acids and their piperidine amides, followed by pharmacologic evaluation of their activity as inverse agonists at the GHS-R1a receptor. Physicochemical properties, pharmacokinetics, safety profiles, and chemical stability under different pH conditions were assessed.","limitations":"The study does not specify the exact experimental models used or provide detailed efficacy data. The evidence strength and study type are unclear, limiting conclusions about clinical relevance."},{"rthcId":"RPEP-02760","title":"Therapeutic utility of antibacterial peptides in wound healing.","authors":"Otvos, Laszlo; Ostorhazi, Eszter","year":2015,"journal":"Expert review of anti-infective therapy, 13(7), 871-81","doi":"10.1586/14787210.2015.1033402","pmid":"25835521","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02761","title":"NUTRALYS(®) pea protein: characterization of in vitro gastric digestion and in vivo gastrointestinal peptide responses relevant to satiety.","authors":"Overduin, Joost; Guérin-Deremaux, Laetitia; Wils, Daniel; Lambers, Tim T","year":2015,"journal":"Food & nutrition research, 59, 25622","doi":"10.3402/fnr.v59.25622","pmid":"25882536","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"NUTRALYS® pea protein transiently aggregates during gastric digestion and exhibits intermediate digestion speed between whey and casein. In vivo, pea protein induced comparable anorexigenic hormone responses (CCK, GLP-1, PYY) and similar integrated ghrelin and insulin responses to whey protein, indicating similar efficacy in triggering satiety signals.","whyItMatters":"Understanding how pea protein influences satiety hormones helps develop sustainable, plant-based foods that can aid appetite control and weight management.","specificNumbers":"","methodology":"The study combined in vitro simulated gastric digestion to compare pea protein with dairy proteins and in vivo monitoring of blood glucose and gastrointestinal hormones in nine male Wistar rats after isocaloric meals containing pea protein, whey protein, or carbohydrates.","limitations":"The study was conducted in rats, which may not fully replicate human digestion and hormonal responses. The sample size was small, and the exact study type and evidence strength were not specified."},{"rthcId":"RPEP-02762","title":"Diversification of the celiac disease α-gliadin complex in wheat: a 33-mer peptide with six overlapping epitopes, evolved following polyploidization.","authors":"Ozuna, Carmen V; Iehisa, Julio C M; Giménez, María J; Alvarez, Juan B; Sousa, Carolina; Barro, Francisco","year":2015,"journal":"The Plant journal : for cell and molecular biology, 82(5), 794-805","doi":"10.1111/tpj.12851","pmid":"25864460","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02763","title":"Substance P stimulates endothelin 1 secretion via endothelin-converting enzyme 1 and promotes melanogenesis in human melanocytes.","authors":"Park, Phil June; Lee, Tae Ryong; Cho, Eun-Gyung","year":2015,"journal":"The Journal of investigative dermatology, 135(2), 551-559","doi":"10.1038/jid.2014.423","pmid":"25268585","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Substance P stimulates melanogenesis in human melanocytes by increasing endothelin 1 (EDN1) secretion via endothelin-converting enzyme 1 (ECE1). EDN1 then activates its receptor EDNRB, leading to increased cAMP levels and activation of melanogenesis-related signaling pathways.","whyItMatters":"Understanding how Substance P regulates pigment production can help develop treatments for pigmentation disorders and improve management of wound-induced hyperpigmentation or pigmented scars.","specificNumbers":"","methodology":"Human melanocytes were treated with varying doses of Substance P in vitro. Gene and protein expression levels of melanogenesis-related factors, neurokinin 1 receptor, EDN1, and EDNRB were measured. siRNA knockdown experiments targeted ECE1, EDN1, and EDNRB to assess their roles in Substance P-induced pigmentation and EDN1 secretion.","limitations":"The study was conducted in vitro using cultured human melanocytes, which may not fully replicate in vivo skin environment. The exact clinical relevance and effects in living organisms remain to be confirmed."},{"rthcId":"RPEP-02764","title":"Stability-indicating HPLC assay for lysine-proline-valine (KPV) in aqueous solutions and skin homogenates.","authors":"Pawar, Kasturi R; Mulabagal, Vanisree; Smith, Forrest; Kolli, Chandra S; Rangari, Vijaya K; Babu, R Jayachandra","year":2015,"journal":"Biomedical chromatography : BMC, 29(5), 716-21","doi":"10.1002/bmc.3347","pmid":"25298219","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The HPLC method achieved excellent linearity with a correlation coefficient of 0.9999 and could detect KPV at concentrations as low as 0.01 μg/mL (LOD) and quantify it at 0.25 μg/mL (LOQ). Accuracy and precision tests showed relative standard deviation values below 2%. Under stress conditions (acid, alkali, and hydrogen peroxide), KPV degraded primarily into lys-pro-diketopiperazine, identified by mass spectrometry. The method successfully separated KPV from both its degradation products and endogenous skin components.","whyItMatters":"Before any peptide can become a drug or topical treatment, scientists need reliable ways to measure its concentration and stability. This validated assay gives researchers a tool to track KPV's behavior in formulations and skin tissue, which is essential for developing KPV-based anti-inflammatory products for skin conditions.","specificNumbers":"","methodology":"Researchers developed a reversed-phase HPLC assay using a Phenomenex C18 column with a gradient mobile phase of trifluoroacetic acid in water and acetonitrile. The method was validated for accuracy, precision, linearity, repeatability, limit of detection, and limit of quantitation. Forced degradation studies exposed KPV to acid, alkali, and hydrogen peroxide stress. Degradation products were identified using flow injection mass spectrometry. The method was also tested in skin homogenate samples.","limitations":"The study focused purely on analytical method development and did not assess whether KPV's degradation products retain any biological activity. Testing was limited to aqueous solutions and skin homogenates, and the method has not been validated in clinical samples or other biological matrices. No in vivo stability data was generated."},{"rthcId":"RPEP-02765","title":"Chronic administration of Glucagon-like peptide-1 receptor agonists improves trabecular bone mass and architecture in ovariectomised mice.","authors":"Pereira, M; Jeyabalan, J; Jørgensen, C S; Hopkinson, M; Al-Jazzar, A; Roux, J P; Chavassieux, P; Orriss, I R; Cleasby, M E; Chenu, C","year":2015,"journal":"Bone, 81, 459-467","doi":"10.1016/j.bone.2015.08.006","pmid":"26314515","tags":[],"studyType":"animal","evidenceStrength":"preliminary","keyFinding":"Chronic administration of the GLP-1 receptor agonists liraglutide (0.3 mg/kg/day) and exenatide (10 μg/kg/day) for four weeks significantly improved trabecular bone mass, connectivity, and structural parameters in ovariectomized (OVX) mice — a standard model of postmenopausal osteoporosis. However, no effect was seen on cortical bone or bone formation in vivo.\n\nImportantly, GLP-1 receptors were found to be expressed in bone marrow cells, osteoclasts, osteoblasts, and osteocytes, indicating that GLP-1 RAs may act directly on bone tissue. Exenatide increased serum calcitonin (which inhibits bone resorption) and decreased sclerostin (which inhibits bone formation), suggesting complex modulation of bone metabolism.","whyItMatters":"With millions of people now taking GLP-1 receptor agonists for diabetes and obesity, understanding their effects on bone is clinically important — especially since some other diabetes drugs (like thiazolidinediones) weaken bones. This study provides reassuring evidence that GLP-1 RAs may actually benefit bone health, and the discovery of GLP-1 receptors on bone cells opens a potential new therapeutic angle for osteoporosis.","specificNumbers":"","methodology":"Female mice were ovariectomized to induce postmenopausal bone loss. Four weeks later, they received daily injections of liraglutide (0.3 mg/kg), exenatide (10 μg/kg), or saline for four weeks. Bone micro-architecture was assessed by micro-CT, and bone formation/resorption were measured by histomorphometry with calcein and alizarin red labeling. Serum calcitonin and sclerostin were measured. GLP-1R expression was evaluated by RT-PCR and immunohistochemistry. In vitro assays tested GLP-1 RA effects on primary osteoclast and osteoblast cultures.","limitations":"This is a mouse study and results may not directly translate to humans. The treatment duration was only four weeks. GLP-1 RAs improved trabecular but not cortical bone, and in vitro effects on bone cells were complex (stimulating osteoclast differentiation while reducing resorption per cell). The doses used may not correspond to human therapeutic doses."},{"rthcId":"RPEP-02766","title":"Ghrelin signalling on food reward: a salient link between the gut and the mesolimbic system.","authors":"Perello, M; Dickson, S L","year":2015,"journal":"Journal of neuroendocrinology, 27(6), 424-34","doi":"10.1111/jne.12236","pmid":"25377898","tags":["ghrelin","food-reward","dopamine"],"studyType":"review","evidenceStrength":"high","keyFinding":"Ghrelin — the hunger hormone produced mainly by the stomach — doesn't just make you hungry, it makes food taste better by activating the brain's reward system. Ghrelin receptors are found not only in hypothalamic areas that control energy balance, but also in the ventral tegmental area (VTA), where the brain's dopamine-driven reward pathways originate. By targeting mesoaccumbal dopamine neurons, ghrelin connects the gut directly to reward circuitry, creating a physiological link between hunger and the pleasurable experience of eating. Importantly, ghrelin's effects on food reward are overlapping with but distinct from its effects on food intake.","whyItMatters":"Understanding why food becomes more rewarding when you're hungry has major implications for obesity, eating disorders, and addiction. This review explains how ghrelin acts as a molecular bridge between your gut and your brain's pleasure centers. This connection also helps explain why GLP-1 drugs that suppress ghrelin's effects may reduce not only appetite but also cravings for alcohol and other rewarding substances.","specificNumbers":"Ghrelin levels peak before meals (preprandially) · Ghrelin receptors found in VTA and other reward areas · Food reward pathways overlap with but are distinct from food intake pathways","methodology":"Narrative review of published research on ghrelin signaling in the mesolimbic reward system, covering neuroanatomy, receptor localization, behavioral studies, and molecular mechanisms linking gut ghrelin to dopamine-mediated food reward.","limitations":"As a narrative review, it synthesizes existing evidence but does not present new experimental data. Much of the mechanistic evidence comes from animal studies, and the extent to which these pathways operate identically in humans is not fully established. The review predates more recent findings on ghrelin's role in non-food reward and addiction behaviors."},{"rthcId":"RPEP-02767","title":"Role of intestinal brush border peptidases in the simulated digestion of milk proteins.","authors":"Picariello, Gianluca; Miralles, Beatriz; Mamone, Gianfranco; Sánchez-Rivera, Laura; Recio, Isidra; Addeo, Francesco; Ferranti, Pasquale","year":2015,"journal":"Molecular nutrition & food research, 59(5), 948-56","doi":"10.1002/mnfr.201400856","pmid":"25688850","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Brush border membrane peptidases significantly increase the degree of hydrolysis of milk proteins after gastroduodenal digestion, producing specific stable peptide domains that may be bioactive or immunogenic. The degree of hydrolysis after BBM digestion reached 70-77%, regardless of the digestion model used.","whyItMatters":"Understanding the role of intestinal brush border enzymes helps improve digestion models and better predicts the bioavailability and potential health effects of dietary peptides from milk proteins.","specificNumbers":"","methodology":"Milk protein samples were subjected to in vitro simulated gastropancreatic digestion using two different protocols, followed by further hydrolysis with porcine jejunal brush border membrane peptidases. Peptide profiles were analyzed using HPLC and mass spectrometry to compare digestion outcomes.","limitations":"The study used in vitro digestion models which may not fully replicate in vivo conditions, and the exact biological effects of the identified peptides were not directly tested."},{"rthcId":"RPEP-02768","title":"GHK Peptide as a Natural Modulator of Multiple Cellular Pathways in Skin Regeneration.","authors":"Pickart, Loren; Vasquez-Soltero, Jessica Michelle; Margolina, Anna","year":2015,"journal":"BioMed research international, 2015, 648108","doi":"10.1155/2015/648108","pmid":"26236730","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GHK peptide modulates multiple cellular pathways involved in skin regeneration by stimulating collagen synthesis and breakdown, regulating metalloproteinases, restoring fibroblast vitality, and attracting immune and endothelial cells to injury sites. It also influences over 4,000 human genes to promote tissue repair and skin health.","whyItMatters":"Understanding GHK's role in skin repair could lead to new treatments for aging skin, chronic wounds, and inflammatory conditions. It highlights a natural molecule that can reset damaged cellular processes.","specificNumbers":"","methodology":"This article is a review summarizing existing research on GHK peptide's biological effects on skin regeneration, wound healing, and gene regulation across various animal models and cosmetic applications.","limitations":"The review does not specify clinical trial data or quantify efficacy in humans, and the evidence strength is unclear. Further controlled studies are needed to confirm therapeutic benefits."},{"rthcId":"RPEP-02769","title":"Ring size in cyclic endomorphin-2 analogs modulates receptor binding affinity and selectivity.","authors":"Piekielna, Justyna; Kluczyk, Alicja; Gentilucci, Luca; Cerlesi, Maria Camilla; Calo', Girolamo; Tomböly, Csaba; Łapiński, Krzysztof; Janecki, Tomasz; Janecka, Anna","year":2015,"journal":"Organic & biomolecular chemistry, 13(21), 6039-46","doi":"10.1039/c5ob00565e","pmid":"25948019","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Reduction of the macrocyclic ring size in cyclic endomorphin-2 analogs increased selectivity and affinity for the MOP receptor. The analog with Dap residue exhibited complete MOP selectivity with subnanomolar affinity, while others showed varying degrees of affinity and selectivity for MOP, DOP, and KOP receptors.","whyItMatters":"Understanding how ring size affects receptor binding helps design more selective opioid peptides, which could lead to better pain treatments with fewer side effects.","specificNumbers":"","methodology":"The study synthesized a series of side chain-to-side chain cyclized opioid peptide analogs with ring sizes from 14 to 17 members. Binding affinities to human recombinant MOP, DOP, and KOP opioid receptors were measured using in vitro calcium mobilization assays in CHO cells expressing these receptors and chimeric G proteins.","limitations":"The study was conducted in vitro using recombinant receptors and cell lines, so in vivo efficacy and safety remain untested. The exact study type and evidence strength were not specified."},{"rthcId":"RPEP-02770","title":"Inflammatory and Metabolic Alterations of Kager's Fat Pad in Chronic Achilles Tendinopathy.","authors":"Pingel, Jessica; Petersen, M Christine H; Fredberg, Ulrich; Kjær, Søren G; Quistorff, Bjørn; Langberg, Henning; Hansen, Jacob B","year":2015,"journal":"PloS one, 10(5), e0127811","doi":"10.1371/journal.pone.0127811","pmid":"25996876","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Patients with chronic Achilles tendinopathy exhibited increased expression of inflammatory marker genes and altered lipid metabolism gene expression in Kager's fat pad compared to healthy controls. Substance P, a pain-related neuropeptide, was detected in one third of patients but absent in controls.","whyItMatters":"Understanding inflammation and metabolic changes in Kager's fat pad may reveal new targets for treating Achilles tendinopathy and improving ankle joint function.","specificNumbers":"","methodology":"Biopsies of Kager's fat pad were collected from 31 patients with chronic Achilles tendinopathy and 13 healthy individuals. Gene expression related to inflammation and lipid metabolism was analyzed using reverse transcription-quantitative PCR.","limitations":"The study does not establish causality between inflammation in Kager's fat pad and Achilles tendinopathy symptoms, and the sample size is relatively small."},{"rthcId":"RPEP-02771","title":"Analysis of the Expression of Tachykinins and Tachykinin Receptors in the Rat Uterus During Early Pregnancy.","authors":"Pinto, Francisco M; Bello, Aixa R; Gallardo-Castro, Manuel; Valladares, Francisco; Almeida, Teresa A; Tena-Sempere, Manuel; Candenas, Luz","year":2015,"journal":"Biology of reproduction, 93(2), 51","doi":"10.1095/biolreprod.115.130617","pmid":"26157068","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"All tachykinins and tachykinin receptors examined were found to be locally synthesized in the uterus of early pregnant rats (Days 1-9). Substance P, neurokinin B, and receptors NK1R and NK3R showed major expression changes during the days surrounding implantation.\n\nThese peptides and receptors were widely distributed in implantation sites and were particularly abundant in decidual cells — the maternal cells that nourish and support the early embryo. Previous work by the same group showed that blocking the NK3R receptor reduced litter size in rats, supporting a functional role for these peptides in reproduction.","whyItMatters":"Embryo implantation failure is a leading cause of infertility and early pregnancy loss. Understanding which molecular signals coordinate this critical process could lead to new diagnostic tools and treatments. This study identifies tachykinin peptides as potential key players in implantation, which could eventually inform fertility treatments or contraceptive strategies.","specificNumbers":"","methodology":"Uterine samples were collected from early pregnant rats (Days 1-9 of pregnancy) and from non-pregnant rats during the proestrus stage of the ovarian cycle. The researchers used three complementary techniques: real-time quantitative RT-PCR to measure mRNA levels, immunohistochemistry to visualize protein location in tissue sections, and Western blot to quantify protein levels of tachykinins and their receptors.","limitations":"This is an animal study in rats, and the findings may not directly translate to human reproductive biology. The study characterized expression patterns but did not perform functional experiments to prove that the tachykinins are required for implantation. Previous work by the group showed NK3R antagonism reduced litter size, but the mechanism linking tachykinin signaling to implantation success was not established in this study."},{"rthcId":"RPEP-02772","title":"Peptidome characterization and bioactivity analysis of donkey milk.","authors":"Piovesana, Susy; Capriotti, Anna Laura; Cavaliere, Chiara; La Barbera, Giorgia; Samperi, Roberto; Zenezini Chiozzi, Riccardo; Laganà, Aldo","year":2015,"journal":"Journal of proteomics, 119, 21-9","doi":"10.1016/j.jprot.2015.01.020","pmid":"25668324","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The study successfully identified 1330 peptides from donkey milk using complementary purification methods. These peptides demonstrated angiotensin-converting enzyme (ACE) inhibitory activity and antioxidant properties, suggesting potential bioactive roles.","whyItMatters":"Understanding the peptide composition and bioactivity of donkey milk can help develop functional foods or nutraceuticals with health benefits, especially for cardiovascular health and oxidative stress management.","specificNumbers":"","methodology":"Two peptide purification strategies were compared: cold acetone precipitation of all proteins and acidic precipitation of caseins. Peptides were then identified via mass spectrometry and their bioactivities assessed through ACE inhibition and antioxidant assays, complemented by bioinformatics analysis.","limitations":"The study did not specify the sample size or provide in vivo validation of the bioactivities, limiting conclusions about health effects in humans. The evidence strength and study type were not clearly defined."},{"rthcId":"RPEP-02773","title":"The short chain fatty acid propionate stimulates GLP-1 and PYY secretion via free fatty acid receptor 2 in rodents.","authors":"Psichas, A; Sleeth, M L; Murphy, K G; Brooks, L; Bewick, G A; Hanyaloglu, A C; Ghatei, M A; Bloom, S R; Frost, G","year":2015,"journal":"International journal of obesity (2005), 39(3), 424-9","doi":"10.1038/ijo.2014.153","pmid":"25109781","tags":[],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Propionate — a short-chain fatty acid produced by gut bacteria when they ferment dietary fiber — triggered the simultaneous release of both GLP-1 and PYY (two appetite-suppressing peptide hormones) from the colon in rats and mice. This effect was mediated through the free fatty acid receptor 2 (FFA2): when the researchers repeated the experiments in mice genetically engineered to lack FFA2, propionate's ability to stimulate gut hormone release was significantly impaired both in isolated cell cultures and in live animals.\n\nThe study confirmed this through multiple approaches: propionate stimulated GLP-1 and PYY secretion from cultured colon cells, and when infused directly into the colon of live rodents, it elevated both hormones in portal vein and jugular vein blood.","whyItMatters":"This study provides a mechanistic explanation for why high-fiber diets suppress appetite — the fiber gets fermented into propionate by gut bacteria, which then triggers the same satiety hormones (GLP-1 and PYY) that blockbuster weight loss drugs target. Understanding this pathway could lead to dietary or prebiotic strategies that naturally boost the body's own appetite-suppressing peptides.","specificNumbers":"Both GLP-1 and PYY elevated in portal + jugular vein plasma · FFA2 knockout significantly attenuated the response · Effects confirmed in vitro and in vivo","methodology":"The researchers used three complementary approaches: (1) isolated colonic crypt cell cultures from wild-type and FFA2 knockout mice to test propionate's direct effect on hormone secretion in vitro; (2) intra-colonic infusion of propionate in live Wistar rats with blood sampling from jugular and portal veins; and (3) the same in vivo protocol in wild-type and FFA2 knockout C57BL6 mice to confirm the receptor's role.","limitations":"This is a rodent study — the magnitude of propionate's effect on GLP-1 and PYY may differ in humans. The study uses direct colonic infusion, which bypasses normal digestion and may produce higher local concentrations than dietary fiber fermentation. The study doesn't measure actual appetite or food intake, only hormone levels."},{"rthcId":"RPEP-02774","title":"Cardiac differentiation potential of human induced pluripotent stem cells in a 3D self-assembling peptide scaffold.","authors":"Puig-Sanvicens, Veronica A C; Semino, Carlos E; Zur Nieden, Nicole I","year":2015,"journal":"Differentiation; research in biological diversity, 90(4-5), 101-10","doi":"10.1016/j.diff.2015.11.002","pmid":"26707885","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Human induced pluripotent stem cells embedded in the RAD16-I peptide hydrogel up-regulate early cardiac genes by up to 105-fold but do not express mature cardiac proteins such as connexin 43 or troponin I, nor do they exhibit contractile activity.","whyItMatters":"Understanding how stem cells differentiate in biomaterial scaffolds is crucial for developing effective bioactive cardiac implants that can repair heart tissue after injury without disrupting heart rhythm.","specificNumbers":"","methodology":"The study cultured human induced pluripotent stem cells with and without ascorbic acid in both adherent conditions and embedded within the RAD16-I peptide hydrogel. Cardiac gene and protein expression, as well as contractile activity, were assessed to evaluate differentiation.","limitations":"The study did not achieve mature cardiac cell differentiation or functional contraction in the 3D scaffold, and in vivo regenerative potential remains untested."},{"rthcId":"RPEP-02775","title":"Do delivery routes of intranasally administered oxytocin account for observed effects on social cognition and behavior? A two-level model.","authors":"Quintana, Daniel S; Alvares, Gail A; Hickie, Ian B; Guastella, Adam J","year":2015,"journal":"Neuroscience and biobehavioral reviews, 49, 182-92","doi":"10.1016/j.neubiorev.2014.12.011","pmid":"25526824","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies three distinct pathways by which intranasally administered oxytocin reaches central and peripheral targets, influencing social cognition and behavior. A two-level model is proposed to explain how these pathways contribute to oxytocin's effects on social information processing, anxiety reduction, and increased social approach behaviors.","whyItMatters":"Understanding how oxytocin reaches the brain and body after nasal administration is crucial for developing effective treatments for social dysfunction in psychiatric disorders. This knowledge can guide better delivery methods and therapeutic strategies.","specificNumbers":"","methodology":"This study is a literature review analyzing nasal anatomy, oxytocin transport routes, and their impact on social cognition and behavior. It synthesizes existing research to propose a theoretical model of oxytocin delivery and action.","limitations":"As a review, the study relies on existing data which may vary in quality and methodology. Direct experimental evidence for some proposed pathways remains limited."},{"rthcId":"RPEP-02776","title":"Intra-articular (IA) ropivacaine microparticle suspensions reduce pain, inflammation, cytokine, and substance p levels significantly more than oral or IA celecoxib in a rat model of arthritis.","authors":"Rabinow, Barrett; Werling, Jane; Bendele, Alison; Gass, Jerome; Bogseth, Roy; Balla, Kelly; Valaitis, Paul; Hutchcraft, Audrey; Graham, Sabine","year":2015,"journal":"Inflammation, 38(1), 40-60","doi":"10.1007/s10753-014-0006-z","pmid":"25189465","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Intra-articular administration of ropivacaine microparticle suspensions significantly reduced pain, histological inflammation, and levels of cytokines IL-18 and IL-1β, as well as substance P, compared to both oral and intra-articular celecoxib in a rat arthritis model.","whyItMatters":"This research suggests that targeted delivery of ropivacaine into joints could provide more effective and longer-lasting pain relief and inflammation control in arthritis, potentially improving treatment safety and efficacy.","specificNumbers":"Significantly reduced: pain (gait + incapacitance tests), IL-18, IL-1β, substance P · Superior to oral celecoxib + IA celecoxib · Pain relief outlasted measurable drug levels · PGPS rat arthritis model","methodology":"Rats with PGPS-induced ankle arthritis were treated with either oral celecoxib, intra-articular celecoxib, or intra-articular ropivacaine microparticles. Pain was assessed using gait analysis and incapacitance testing, while inflammation and cytokine levels were measured histologically and biochemically.","limitations":"The study was conducted in a rat model, which may not fully replicate human arthritis. The exact study type and evidence strength were not specified, limiting assessment of clinical applicability."},{"rthcId":"RPEP-02777","title":"Dissecting the Immune Response Elicited by WbALT-2, ALT MAP in Clinical Populations and Mouse Model: A Prophylactic Measure Against Lymphatic Filariasis.","authors":"Ramanathan, Aparnaa; Immanuel, Christiana; Rao, Donthamsetty Nageswara; Kaliraj, Perumal","year":2015,"journal":"Lymphatic research and biology, 13(2), 120-5","doi":"10.1089/lrb.2014.0034","pmid":"26091407","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The multiple antigenic peptide (ALT MAP) constructed from immunodominant epitopes of the ALT-2 antigen elicited strong humoral immune responses, particularly elevated IgG1 and IgG2 antibody levels, in both clinical sera and mouse models. Although T cell proliferation was low, the ALT MAP stimulated innate immunity potentially through complement activation, indicating its potential as a prophylactic vaccine candidate against lymphatic filariasis.","whyItMatters":"Lymphatic filariasis is a debilitating parasitic disease with limited preventive options. Developing an effective peptide-based vaccine could provide a new tool to protect at-risk populations and reduce disease burden.","specificNumbers":"","methodology":"The study involved synthesizing the ALT MAP peptide via solid phase peptide synthesis and testing its reactivity against sera from endemic human populations and mice. Immune responses were assessed by measuring antibody isotypes and T cell proliferation to evaluate the vaccine candidate's immunogenicity.","limitations":"The study did not include parasite challenge experiments to directly demonstrate protective efficacy, and the T cell response was limited, possibly due to epitope arrangement or MHC restrictions."},{"rthcId":"RPEP-02778","title":"Human lactoferricin derived di-peptides deploying loop structures induce apoptosis specifically in cancer cells through targeting membranous phosphatidylserine.","authors":"Riedl, Sabrina; Leber, Regina; Rinner, Beate; Schaider, Helmut; Lohner, Karl; Zweytick, Dagmar","year":2015,"journal":"Biochimica et biophysica acta, 1848(11 Pt A), 2918-31","doi":"10.1016/j.bbamem.2015.07.018","pmid":"26239537","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Di-peptide and di-retro-peptide derivatives of human lactoferricin (hLFcin) achieved up to 100% cancer cell toxicity at 20 μM concentration across melanoma (A375), glioblastoma (U-87mg), and rhabdomyosarcoma cell lines. Compared to the parent hLFcin sequence, derivatives showed 10-fold increased toxicity on melanoma and 2-3-fold on glioblastoma.\n\nStructural analysis revealed a critical insight: peptides with loop structures selectively killed cancer cells via apoptosis (confirmed by caspase 3/7 activation, apoptotic blebbing, and DNA fragmentation), while peptides with α-helical structures without loops killed non-specifically through rapid membrane lysis (necrosis). Phosphatidylserine — uniquely exposed on cancer cell surfaces — was identified as the primary membrane target for cancer-selective peptides. Other negatively charged molecules (sialic acid, heparan/chondroitin sulfate) had minor impact on activity.","whyItMatters":"Cancer-selective killing is the holy grail of oncology — destroying tumors while sparing healthy tissue. This study identifies a clear structural rule: loop-shaped peptides target cancer-specific phosphatidylserine and trigger clean apoptotic death, while helical peptides cause nonselective damage. This provides a rational design framework for building peptide-based cancer drugs from naturally derived milk protein fragments, potentially offering a new class of targeted cancer therapeutics with fewer side effects than chemotherapy.","specificNumbers":"","methodology":"Researchers designed multiple lactoferricin-derived peptides of 9-11 amino acids, then created di-peptide (repeated) and di-retro-peptide (retro-repeated) versions. These were tested against melanoma (A375), glioblastoma (U-87mg), and rhabdomyosarcoma cancer cell lines and compared with normal cells. Cell killing was assessed by viability assays. Apoptosis was confirmed through caspase 3/7 activation, membrane blebbing, and DNA fragmentation analysis. Peptide structures were characterized by circular dichroism. Membrane interactions were studied using phosphatidylserine model membranes and differential scanning calorimetry.","limitations":"This is entirely an in vitro study using cancer cell lines, which do not capture the complexity of tumors growing in living tissue with blood supply, immune cells, and microenvironment. The peptides' stability in blood, ability to reach tumors, and effects on normal tissues in vivo are unknown. The 20 μM concentration needed for 100% killing may be difficult to achieve at tumor sites. Only three cancer types were tested. Long-term toxicity and immunogenicity were not assessed."},{"rthcId":"RPEP-02779","title":"Neuro-peptide treatment with Cerebrolysin improves the survival of neural stem cell grafts in an APP transgenic model of Alzheimer disease.","authors":"Rockenstein, Edward; Desplats, Paula; Ubhi, Kiren; Mante, Michael; Florio, Jazmin; Adame, Anthony; Winter, Stefan; Brandstaetter, Hemma; Meier, Dieter; Masliah, Eliezer","year":2015,"journal":"Stem cell research, 15(1), 54-67","doi":"10.1016/j.scr.2015.04.008","pmid":"26209890","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02780","title":"Effects and interactions of tachykinins and dynorphin on FSH and LH secretion in developing and adult rats.","authors":"Ruiz-Pino, F; Garcia-Galiano, D; Manfredi-Lozano, M; Leon, S; Sánchez-Garrido, M A; Roa, J; Pinilla, L; Navarro, V M; Tena-Sempere, M","year":2015,"journal":"Endocrinology, 156(2), 576-88","doi":"10.1210/en.2014-1026","pmid":"25490143","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Key age- and sex-dependent findings on peptide control of reproductive hormones:\n\n- Neurokinin B (via NK3R agonist senktide) stimulated FSH secretion in both male and female prepubertal rats\n- Adult female rats showed LH but not FSH responses to senktide; adult males showed neither\n- Blocking dynorphin with nor-binaltorphimine restored LH responses in adult males and FSH responses in adult females\n- Basal LH and FSH levels increased when dynorphin was blocked in adult males\n- Substance P and neurokinin A also stimulated gonadotropins prepubertally but had reduced effects in adults\n- Dynorphin and its receptor (κ-opioid receptor) gene expression was higher in prepubertal males than females in the mediobasal hypothalamus","whyItMatters":"The KNDy (kisspeptin/neurokinin B/dynorphin) neuron system is increasingly recognized as a master regulator of reproduction. Understanding how these peptides interact differently at various life stages is crucial for developing peptide-based treatments for conditions like precocious puberty, delayed puberty, and infertility. The finding that dynorphin acts as a brake on reproductive signaling in adults has direct implications for hormonal therapies.","specificNumbers":"","methodology":"Researchers administered pharmacological agonists of tachykinin receptors (NK1R, NK2R, NK3R) and a dynorphin receptor antagonist to male and female Wistar rats at various postnatal developmental stages. Blood samples measured FSH and LH responses. Gene expression of dynorphin (Pdyn) and its receptor (Opkr1) was assessed in hypothalamic tissue using RT-qPCR.","limitations":"This is a rat study, and reproductive neuroendocrine signaling differs between rodents and humans. The pharmacological approach (using agonists and antagonists) provides functional evidence but doesn't fully capture the complexity of natural peptide interactions within KNDy neurons. The study focused on acute hormone responses and did not assess long-term effects. Sex differences in human KNDy signaling may not mirror those seen in rats."},{"rthcId":"RPEP-02781","title":"Identification of Anticancer Peptides from Bovine Milk Proteins and Their Potential Roles in Management of Cancer: A Critical Review.","authors":"Sah, B N P; Vasiljevic, T; McKechnie, S; Donkor, O N","year":2015,"journal":"Comprehensive reviews in food science and food safety, 14(2), 123-138","doi":"10.1111/1541-4337.12126","pmid":"33401807","tags":[],"studyType":"review","evidenceStrength":"moderate","keyFinding":"A comprehensive review of bovine milk proteins identified numerous peptide sequences with potential anticancer activity. Using the AntiCP prediction server, researchers found that caseins and whey proteins contain a remarkable number of peptide fragments predicted to have antitumor properties. Proline dominated at key positions in casein-derived anticancer peptides, while lysine was prominent in whey-derived ones.\n\nThese bioactive peptides can be naturally released during gastrointestinal digestion or through fermentation processes used in making yogurt, cheese, and other dairy products. While the epidemiological evidence linking dairy consumption to cancer risk remains inconsistent, the peptide-level data suggests milk proteins are a promising source of natural anticancer candidates.","whyItMatters":"Conventional cancer treatments like chemotherapy are expensive and have severe side effects. If peptides naturally present in or released from milk proteins have genuine anticancer properties, they could represent a safer, more accessible approach to cancer prevention. This review bridges food science and oncology, showing that everyday dairy foods may contain bioactive peptides with therapeutic potential.","specificNumbers":"Proline: dominant amino acid in casein-derived anticancer peptides · Lysine: dominant in whey-derived anticancer peptides · AntiCP database used for computational screening","methodology":"Critical literature review of published studies on anticancer peptides from bovine milk proteins, supplemented by computational analysis using the AntiCP web-based prediction server to screen casein and whey protein sequences for potential anticancer peptide fragments.","limitations":"Primarily based on computational predictions (in silico) and preclinical lab studies — no clinical trials in humans. The epidemiological evidence linking dairy consumption to cancer risk is inconsistent and sometimes contradictory. Predicted anticancer activity does not guarantee real-world efficacy. Bioavailability of these peptides after oral consumption is not well established."},{"rthcId":"RPEP-02782","title":"Tachykinins Processing is Significantly Impaired in PC1 and PC2 Mutant Mouse Spinal Cord S9 Fractions.","authors":"Saidi, Mouna; Kamali, Soufiane; Ruiz, Alberto Orduna; Beaudry, Francis","year":2015,"journal":"Neurochemical research, 40(11), 2304-16","doi":"10.1007/s11064-015-1720-0","pmid":"26373413","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Both PC1 and PC2 enzymes mediate the C-terminal processing of protachykinin peptides, including Substance P and its precursor Tachykinin 58-71. Mutations in PC1 and PC2 resulted in over 50% reduction in the formation rate of these peptides in mouse spinal cord S9 fractions.","whyItMatters":"Understanding how PC1 and PC2 enzymes process protachykinin peptides is crucial for grasping the molecular mechanisms of pain perception. This knowledge could inform the development of new pain treatments targeting peptide maturation pathways.","specificNumbers":"","methodology":"The study used spinal cord S9 fractions from wild type, PC1(-/+) and PC2(-/+) mutant mice. Full-length Tachykinin 20-68 and Tachykinin 58-78 peptides were incubated for 30 minutes with these fractions. Mass spectrometry identified and quantified specific C-terminal peptide fragments to assess proteolytic processing.","limitations":"The study was conducted in vitro using spinal cord fractions, which may not fully replicate in vivo conditions. The exact physiological consequences of reduced peptide processing in mutant mice were not assessed."},{"rthcId":"RPEP-02783","title":"Potentiating effects of GHRH analogs on the response to chemotherapy.","authors":"Schally, Andrew V; Perez, Roberto; Block, Norman L; Rick, Ferenc G","year":2015,"journal":"Cell cycle (Georgetown, Tex.), 14(5), 699-704","doi":"10.1080/15384101.2015.1010893","pmid":"25648497","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GHRH antagonists potentiate the efficacy of chemotherapy agents such as doxorubicin, docetaxel, 5-FU, irinotecan, and cisplatin by reducing tumor growth, inflammatory signaling, drug resistance gene expression, cancer stem-cell markers, and efflux pump function in various cancer models including triple negative breast cancer, non-small cell lung cancer, and colorectal cancer.","whyItMatters":"This research suggests that targeting GHRH receptors could improve chemotherapy effectiveness, potentially leading to better cancer treatment outcomes and overcoming drug resistance.","specificNumbers":"","methodology":"The study used in vitro cancer cell lines and in vivo mouse xenograft models treated with GHRH antagonists alone or combined with chemotherapy drugs to assess tumor growth, gene expression, cell cycle arrest, and drug resistance mechanisms.","limitations":"The study was conducted primarily in cell lines and mouse models, so clinical efficacy and safety in humans remain to be established."},{"rthcId":"RPEP-02784","title":"Ghrelin's Orexigenic Effect Is Modulated via a Serotonin 2C Receptor Interaction.","authors":"Schellekens, Harriët; De Francesco, Pablo N; Kandil, Dalia; Theeuwes, Wessel F; McCarthy, Triona; van Oeffelen, Wesley E P A; Perelló, Mario; Giblin, Linda; Dinan, Timothy G; Cryan, John F","year":2015,"journal":"ACS chemical neuroscience, 6(7), 1186-97","doi":"10.1021/cn500318q","pmid":"25727097","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The GHS-R1a receptor and 5-HT2C receptor physically interact, modulating ghrelin's orexigenic effect. Blocking 5-HT2C receptor signaling potentiates ghrelin-induced food intake in vivo, while activation by lorcaserin attenuates it, demonstrating a biologically significant receptor interaction.","whyItMatters":"Understanding how serotonin 2C receptors modulate ghrelin's appetite-stimulating effects could lead to improved treatments for obesity by targeting these receptor interactions to control food intake.","specificNumbers":"","methodology":"The study used in vitro cell lines expressing both GHS-R1a and 5-HT2C receptors to demonstrate receptor interaction via flow cytometry FRET. Colocalization was confirmed in cultured rat neurons. In vivo experiments assessed the effect of 5-HT2C receptor blockade or activation on ghrelin-induced food intake.","limitations":"The study's in vivo experiments were limited to animal models, and the exact clinical relevance in humans remains to be established. The study type and evidence strength were not clearly defined."},{"rthcId":"RPEP-02785","title":"Dietary Supplementation with Specific Collagen Peptides Has a Body Mass Index-Dependent Beneficial Effect on Cellulite Morphology.","authors":"Schunck, Michael; Zague, Vivian; Oesser, Steffen; Proksch, Ehrhardt","year":2015,"journal":"Journal of medicinal food, 18(12), 1340-8","doi":"10.1089/jmf.2015.0022","pmid":"26561784","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Daily oral supplementation with 2.5 g of specific bioactive collagen peptides over six months significantly decreased cellulite severity and skin waviness, and improved dermal density in women with normal BMI; similar but less pronounced effects were observed in overweight women.","whyItMatters":"This study provides evidence that oral collagen peptides can improve skin structure and reduce cellulite, offering a non-invasive approach to skin health and cosmetic concerns related to cellulite.","specificNumbers":"","methodology":"A double-blind, placebo-controlled clinical trial involving 105 women aged 24-50 with moderate cellulite randomized participants to receive either 2.5 g of collagen peptides or placebo daily for six months. Cellulite degree, skin waviness, dermal density, and subcutaneous borderline length were measured at baseline, 3 months, and 6 months.","limitations":"The study did not specify the exact study type or evidence strength, and the cellulite improvement in overweight women was less pronounced. The subcutaneous borderline shortening did not reach statistical significance compared to placebo."},{"rthcId":"RPEP-02786","title":"Fluorescently labeled adrenomedullin allows real-time monitoring of adrenomedullin receptor trafficking in living cells.","authors":"Schönauer, Ria; Kaiser, Anette; Holze, Cathleen; Babilon, Stefanie; Köbberling, Johannes; Riedl, Bernd; Beck-Sickinger, Annette G","year":2015,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 21(12), 905-12","doi":"10.1002/psc.2833","pmid":"26767744","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Fluorescently labeled adrenomedullin peptides enabled real-time visualization of the AM1 receptor complex internalization and trafficking to lysosomes in living cells. The N-terminal region of adrenomedullin is not critical for receptor internalization behavior.","whyItMatters":"Understanding how adrenomedullin and its receptor are internalized and degraded helps clarify their role in cardiovascular regulation and could inform therapeutic strategies targeting this pathway.","specificNumbers":"","methodology":"The study synthesized full-length and truncated adrenomedullin peptides labeled with a fluorescent dye using solid phase peptide synthesis and click chemistry. Live cells co-expressing fluorescently tagged receptor components were observed using fluorescence microscopy to track ligand-receptor internalization and lysosomal routing.","limitations":"The study does not specify the quantitative strength of evidence or in vivo relevance, and the exact physiological consequences of receptor trafficking were not explored."},{"rthcId":"RPEP-02787","title":"Determination of growth hormone releasing peptides metabolites in human urine after nasal administration of GHRP-1, GHRP-2, GHRP-6, Hexarelin, and Ipamorelin.","authors":"Semenistaya, Ekaterina; Zvereva, Irina; Thomas, Andreas; Thevis, Mario; Krotov, Grigory; Rodchenkov, Grigory","year":2015,"journal":"Drug testing and analysis, 7(10), 919-25","doi":"10.1002/dta.1787","pmid":"25869809","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Metabolites of GHRP-1, GHRP-2, GHRP-6, Hexarelin, and Ipamorelin were identified in urine after nasal administration, with detection windows ranging from 12 to 47 hours depending on the peptide and metabolite. Parent compounds were often undetectable while metabolites remained present for longer periods.","whyItMatters":"Understanding the metabolism and excretion timelines of GHRPs is crucial for developing reliable anti-doping tests and ensuring fair competition in sports. It also informs how these peptides behave in the body after nasal administration.","specificNumbers":"","methodology":"Each peptide was administered nasally to a single volunteer. Urine samples were collected for 48 hours post-administration, processed via solid-phase extraction, and analyzed using nano-liquid chromatography coupled with high-resolution mass spectrometry to identify parent compounds and metabolites.","limitations":"The study involved only one volunteer per peptide, limiting generalizability. The exact study type and evidence strength were not specified, and nasal administration may differ from other routes."},{"rthcId":"RPEP-02788","title":"Thymosin α1 modifies podosome architecture and promptly stimulates the expression of podosomal markers in mature macrophages.","authors":"Serafino, Annalucia; Andreola, Federica; Pittaluga, Eugenia; Krasnowska, Ewa K; Nicotera, Giuseppe; Sferrazza, Gianluca; Sinibaldi Vallebona, Paola; Pierimarchi, Pasquale; Garaci, Enrico","year":2015,"journal":"Expert opinion on biological therapy, 15 Suppl 1, S101-16","doi":"10.1517/14712598.2015.1024221","pmid":"26098689","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Thymosin α1 rapidly stimulates the assembly and disassembly of podosomes in mature human macrophages within one hour, enhancing their motility, invasion, and chemotaxis capabilities.","whyItMatters":"Understanding how thymosin α1 modulates macrophage podosomes helps clarify its role in innate immunity and supports its potential use in treating immunodeficiency disorders.","specificNumbers":"","methodology":"Researchers used microscopy techniques including optical, scanning electron, time-lapse, and confocal microscopy, along with Western blotting, migration assays, and zymography to analyze the effects of thymosin α1 on human monocyte-derived macrophages in vitro.","limitations":"The study was conducted in vitro on human macrophages, so in vivo effects and clinical relevance require further investigation."},{"rthcId":"RPEP-02789","title":"The Inhibitory Effect of Botulinum Toxin Type A on Rat Pyloric Smooth Muscle Contractile Response to Substance P In Vitro.","authors":"Shao, Yu-Feng; Xie, Jun-Fan; Ren, Yin-Xiang; Wang, Can; Kong, Xiang-Pan; Zong, Xiao-Jian; Fan, Lin-Lan; Hou, Yi-Ping","year":2015,"journal":"Toxins, 7(10), 4143-56","doi":"10.3390/toxins7104143","pmid":"26501321","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BTX-A inhibits Substance P release from enteric nerve terminals and directly reduces Substance P-induced contractility of rat pyloric smooth muscle in a concentration- and time-dependent manner. This inhibition occurs even when muscarinic cholinergic receptors are blocked.","whyItMatters":"Understanding how BTX-A modulates neuropeptide-induced muscle contractions can inform its therapeutic use in gastrointestinal disorders involving pyloric dysfunction and guide peptide-targeted treatments.","specificNumbers":"","methodology":"The study used in vitro rat pyloric muscle preparations treated with BTX-A at varying concentrations and durations. Contractile responses to electrical field stimulation and Substance P were measured, alongside immunohistochemical analysis of Substance P and NK1 receptor distributions.","limitations":"The study was conducted in vitro on rat tissue, which may not fully replicate in vivo conditions or human physiology. The exact clinical relevance and long-term effects remain to be established."},{"rthcId":"RPEP-02790","title":"Facilitated spinal neuropeptide signaling and upregulated inflammatory mediator expression contribute to postfracture nociceptive sensitization.","authors":"Shi, Xiaoyou; Guo, Tian-Zhi; Wei, Tzuping; Li, Wen-Wu; Clark, David J; Kingery, Wade S","year":2015,"journal":"Pain, 156(10), 1852-1863","doi":"10.1097/j.pain.0000000000000204","pmid":"25932690","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tibia fracture in rats caused increased spinal cord levels of substance P and CGRP neuropeptides, which upregulated inflammatory mediators (TNF, IL-1, IL-6, CCL2, nerve growth factor), resulting in nociceptive sensitization. Mice lacking SP or CGRP receptors showed reduced inflammatory mediator expression and less pain behavior. Intrathecal antagonists targeting these pathways alleviated pain.","whyItMatters":"Understanding how neuropeptide signaling drives spinal inflammation and pain after fractures can help develop targeted therapies for complex regional pain syndrome and other chronic pain conditions.","specificNumbers":"","methodology":"The study used a rat tibia fracture model to measure pain behaviors and spinal cord neuropeptide and inflammatory mediator levels at 4 weeks post-fracture. Intrathecal injections of receptor antagonists were administered to assess effects on pain. Transgenic mice lacking specific neuropeptide signaling components were also evaluated for pain and inflammatory responses.","limitations":"The study was conducted in rodent models, which may not fully replicate human complex regional pain syndrome. The exact translation of neuropeptide and inflammatory mediator roles to clinical settings requires further investigation."},{"rthcId":"RPEP-02791","title":"Role of the Paraventricular Nucleus of the Hypothalamus in the Sympathoexcitatory Effects of Leptin.","authors":"Shi, Zhigang; Li, Baoxin; Brooks, Virginia L","year":2015,"journal":"Hypertension (Dallas, Tex. : 1979), 66(5), 1034-41","doi":"10.1161/HYPERTENSIONAHA.115.06017","pmid":"26370892","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Intracerebroventricular leptin increased lumbar sympathetic nerve activity (LSNA), heart rate, and mean arterial pressure in anesthetized rats. Inhibiting the paraventricular nucleus with muscimol completely reversed all of leptin's effects, confirming this brain region as essential.\n\nThe mechanism involves three parallel pathways converging on the paraventricular nucleus: (1) increased glutamatergic excitatory drive, (2) increased melanocortin 3/4 receptor activation by α-melanocyte-stimulating hormone, and (3) withdrawal of tonic neuropeptide Y inhibitory inputs from the arcuate nucleus. Critically, the melanocortin excitatory effect only manifested when neuropeptide Y Y1 receptor signaling was simultaneously blocked, revealing a gating mechanism where neuropeptide Y withdrawal is required for melanocortin activation to drive sympathetic output.","whyItMatters":"Obesity-related hypertension is a major health problem, and elevated leptin levels in obese individuals may directly contribute to high blood pressure through sympathetic activation. Understanding the specific neuropeptide pathways — especially that neuropeptide Y withdrawal is required for melanocortin-driven blood pressure increases — could reveal new drug targets for treating hypertension in obese patients without affecting other leptin functions.","specificNumbers":"","methodology":"Researchers used anesthetized male Sprague-Dawley rats and delivered leptin via intracerebroventricular injection. They measured lumbar sympathetic nerve activity, heart rate, and mean arterial pressure. To dissect the neural circuitry, they systematically injected pharmacological blockers into the paraventricular nucleus — muscimol (general inhibitor), SHU9119 (melanocortin 3/4 receptor blocker), kynurenate (glutamate receptor blocker), and neuropeptide Y Y1 receptor antagonist — alone and in combination, to determine each pathway's contribution.","limitations":"The study was conducted in anesthetized rats, and anesthesia can alter neural signaling and cardiovascular reflexes. The findings may not directly translate to awake animals or humans. Intracerebroventricular leptin delivery produces brain-wide exposure rather than targeting specific nuclei. Sample sizes for individual experimental groups are not reported in the abstract. Only male rats were studied."},{"rthcId":"RPEP-02792","title":"Therapeutic applications of ghrelin agonists in the treatment of gastroparesis.","authors":"Shin, Andrea; Wo, John M","year":2015,"journal":"Current gastroenterology reports, 17(2), 430","doi":"10.1007/s11894-015-0430-8","pmid":"25702264","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The ghrelin receptor agonist RM-131 significantly accelerated gastric emptying in patients with type 1 and type 2 diabetes and delayed gastric emptying. RM-131 also reduced total Gastroparesis Cardinal Symptom Index-Daily Diary (GCSI-DD) scores among type 1 diabetic patients. Earlier intravenous administration of TZP-101 showed symptom improvement, but oral TZP-102 did not confirm these effects.","whyItMatters":"Gastroparesis currently lacks effective treatments, so ghrelin agonists offer a potential new therapy to improve patient quality of life by enhancing stomach motility and reducing symptoms.","specificNumbers":"","methodology":"The study reviewed clinical trials involving ghrelin receptor agonists in diabetic gastroparesis patients, comparing intravenous and oral administration effects on gastric emptying and symptom scores.","limitations":"The evidence strength and study types are not clearly defined, and some ghrelin agonists showed inconsistent results depending on administration route. Further large-scale, controlled trials are needed."},{"rthcId":"RPEP-02793","title":"Parathyroid hormone: anabolic and catabolic actions on the skeleton.","authors":"Silva, Barbara C; Bilezikian, John P","year":2015,"journal":"Current opinion in pharmacology, 22, 41-50","doi":"10.1016/j.coph.2015.03.005","pmid":"25854704","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02794","title":"Substance p regulates puberty onset and fertility in the female mouse.","authors":"Simavli, Serap; Thompson, Iain R; Maguire, Caroline A; Gill, John C; Carroll, Rona S; Wolfe, Andrew; Kaiser, Ursula B; Navarro, Víctor M","year":2015,"journal":"Endocrinology, 156(6), 2313-22","doi":"10.1210/en.2014-2012","pmid":"25856429","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Substance P, via its receptor NK1R, stimulates gonadotropin release before puberty, advancing puberty onset and supporting fertility in female mice. Tac1 knockout females lacking Substance P exhibit delayed puberty and subfertility characterized by fewer ovarian follicles and smaller litter sizes.","whyItMatters":"Understanding how Substance P regulates puberty and fertility could help clarify neuroendocrine control of reproduction and identify targets for treating reproductive disorders.","specificNumbers":"","methodology":"The study used pharmacological activation of NK1R receptors with selective agonists in prepubertal female mice and analyzed gene expression in the arcuate nucleus. It also compared puberty timing and fertility parameters in Tac1 knockout mice lacking Substance P versus wild-type controls.","limitations":"The study was conducted in mice, so findings may not fully translate to humans. The exact mechanisms by which Substance P influences Kiss1 neurons require further elucidation."},{"rthcId":"RPEP-02795","title":"N-acetyl-l-tryptophan, but not N-acetyl-d-tryptophan, rescues neuronal cell death in models of amyotrophic lateral sclerosis.","authors":"Sirianni, Ana C; Jiang, Jiying; Zeng, Jiang; Mao, Lilly L; Zhou, Shuanhu; Sugarbaker, Peter; Zhang, Xinmu; Li, Wei; Friedlander, Robert M; Wang, Xin","year":2015,"journal":"Journal of neurochemistry, 134(5), 956-68","doi":"10.1111/jnc.13190","pmid":"26031348","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"N-acetyl-l-tryptophan (L-NAT), but not N-acetyl-d-tryptophan (D-NAT), significantly rescues motor neuron-like cells and primary motor neurons from cell death in ALS models. L-NAT inhibits mitochondrial cytochrome c release, reduces secretion of inflammatory factors Substance P and IL-1β, and prevents activation of apoptotic caspases and proteasomal dysfunction.","whyItMatters":"These findings highlight L-NAT as a promising neuroprotective agent that targets multiple pathological pathways in ALS, potentially leading to new therapeutic approaches for this currently incurable disease.","specificNumbers":"","methodology":"The study used NSC-34 motor neuron-like cells and primary motor neurons exposed to ALS-related stressors to measure cell death. Molecular modeling analyzed binding stability of L-NAT to neurokinin-1 receptor. Biochemical assays quantified secretion of inflammatory molecules, mitochondrial protein release, caspase activation, and proteasome activity.","limitations":"The study was conducted in cell models, which may not fully replicate human ALS pathology. The exact in vivo efficacy and safety of L-NAT require further investigation."},{"rthcId":"RPEP-02796","title":"Duodenocutaneous fistula in rats as a model for \"wound healing-therapy\" in ulcer healing: the effect of pentadecapeptide BPC 157, L-nitro-arginine methyl ester and L-arginine.","authors":"Skorjanec, S; Kokot, A; Drmic, D; Radic, B; Sever, M; Klicek, R; Kolenc, D; Zenko, A; Lovric Bencic, M; Belosic Halle, Z; Situm, A; Zivanovic Posilovic, G; Masnec, S; Suran, J; Aralica, G; Seiwerth, S; Sikiric, P","year":2015,"journal":"Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 66(4), 581-90","doi":null,"pmid":"26348082","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BPC 157 administered either intraperitoneally or orally at doses of 10 μg/kg or 10 ng/kg fully counteracted persistent duodenocutaneous fistulas, reduced mortality from 40% to 0%, and restored sphincter function in rats within 7 days. L-NAME worsened outcomes, increasing mortality to 70%, while L-arginine improved healing but more slowly. BPC 157 also neutralized the negative effects of L-NAME.","whyItMatters":"This research highlights BPC 157 as a potential new therapy for difficult-to-heal duodenal ulcers and fistulas by promoting wound healing and restoring digestive function, which could improve patient outcomes.","specificNumbers":"","methodology":"Rats with surgically induced duodenocutaneous fistulas were treated with BPC 157, L-NAME, L-arginine, or combinations thereof for 21 days via intraperitoneal injection or oral administration. Fistula healing, sphincter pressure, and mortality were monitored to assess treatment effects.","limitations":"The study was conducted in rats, so results may not fully translate to humans. The exact mechanisms of BPC 157’s interaction with the nitric oxide system require further clarification. The study type and evidence strength were not specified."},{"rthcId":"RPEP-02797","title":"A Tetrameric Peptide Derived from Bovine Lactoferricin Exhibits Specific Cytotoxic Effects against Oral Squamous-Cell Carcinoma Cell Lines.","authors":"Solarte, Víctor A; Rosas, Jaiver E; Rivera, Zuly J; Arango-Rodríguez, Martha L; García, Javier E; Vernot, Jean-Paul","year":2015,"journal":"BioMed research international, 2015, 630179","doi":"10.1155/2015/630179","pmid":"26609531","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The tetrameric peptide LfcinB(20-25)4, containing the RRWQWR motif, demonstrated over 90% cytotoxicity against oral squamous-cell carcinoma cell lines CAL27 and SCC15, with high specificity and rapid necrotic effects within one hour of treatment.","whyItMatters":"This peptide shows promise as a targeted therapeutic agent for oral cancer, potentially offering a fast-acting treatment that selectively kills cancer cells while sparing healthy tissue.","specificNumbers":"","methodology":"Short linear peptides derived from cyclic bovine lactoferricin were synthesized and tested in vitro against two oral squamous-cell carcinoma cell lines (CAL27 and SCC15) and a non-tumorigenic control cell line (Het-1A) to assess cytotoxicity and specificity.","limitations":"The study was conducted in vitro, so the peptide's effectiveness and safety in living organisms remain untested; the study type and evidence strength were not specified."},{"rthcId":"RPEP-02798","title":"Substance P excites GABAergic neurons in the mouse central amygdala through neurokinin 1 receptor activation.","authors":"Sosulina, L; Strippel, C; Romo-Parra, H; Walter, A L; Kanyshkova, T; Sartori, S B; Lange, M D; Singewald, N; Pape, H-C","year":2015,"journal":"Journal of neurophysiology, 114(4), 2500-8","doi":"10.1152/jn.00883.2014","pmid":"26334021","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Substance P depolarizes and increases firing of GABAergic neurons in the lateral central amygdala via neurokinin 1 receptor activation, predominantly affecting PKCδ-negative neurons and enhancing GABAergic synaptic activity.","whyItMatters":"Understanding how Substance P modulates inhibitory neurons in the amygdala helps clarify mechanisms underlying anxiety and stress responses, potentially guiding peptide-targeted therapies.","specificNumbers":"","methodology":"Using brain slices from genetically modified mice that label GABAergic neurons, the study applied Substance P and receptor agonists/antagonists to measure neuronal electrical responses and receptor localization via immunofluorescence.","limitations":"The study was conducted in vitro using mouse brain slices, which may not fully represent in vivo conditions or human brain function."},{"rthcId":"RPEP-02799","title":"Effects of growth hormone-releasing hormone on visceral fat, metabolic, and cardiovascular indices in human studies.","authors":"Stanley, Takara L; Grinspoon, Steven K","year":2015,"journal":"Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society, 25(2), 59-65","doi":"10.1016/j.ghir.2014.12.005","pmid":"25555516","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"This review synthesizes evidence that growth hormone-releasing hormone (GHRH) treatment significantly reduces visceral fat, improves dyslipidemia, and lowers cardiovascular risk markers in both HIV-infected patients and individuals with general obesity. The underlying mechanism involves a vicious cycle: excess visceral fat suppresses GH secretion (through hyperinsulinemia, elevated free fatty acids, increased somatostatin tone, and reduced ghrelin), and low GH further promotes visceral fat accumulation due to decreased lipolysis. GHRH breaks this cycle by restoring endogenous basal and pulsatile GH secretion without altering pulse frequency — a more physiological approach than direct GH injection.","whyItMatters":"Visceral fat is the most metabolically dangerous type of fat, driving dyslipidemia, inflammation, and cardiovascular disease. Unlike direct GH administration (which carries side effects like insulin resistance and fluid retention), GHRH works by restoring the body's own GH production patterns. This review provides evidence that targeting the GH-visceral fat cycle with GHRH could address multiple cardiometabolic risk factors simultaneously.","specificNumbers":"","methodology":"Narrative review synthesizing data from clinical studies in HIV-infected populations (who commonly develop visceral lipodystrophy) and generally obese individuals. Reviews evidence on GHRH's effects on visceral fat, lipid profiles, inflammatory markers, and cardiovascular risk indices.","limitations":"Narrative review, not a systematic review or meta-analysis. Most clinical data come from HIV-lipodystrophy populations, which may not generalize to all forms of obesity. Long-term efficacy and safety data for GHRH treatment are lacking. Does not address potential risks of sustained GH/IGF-1 elevation."},{"rthcId":"RPEP-02800","title":"Pentadecapeptide BPC 157 Reduces Bleeding and Thrombocytopenia after Amputation in Rats Treated with Heparin, Warfarin, L-NAME and L-Arginine.","authors":"Stupnisek, Mirjana; Kokot, Antonio; Drmic, Domagoj; Hrelec Patrlj, Masa; Zenko Sever, Anita; Kolenc, Danijela; Radic, Bozo; Suran, Jelena; Bojic, Davor; Vcev, Aleksandar; Seiwerth, Sven; Sikiric, Predrag","year":2015,"journal":"PloS one, 10(4), e0123454","doi":"10.1371/journal.pone.0123454","pmid":"25897838","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BPC 157 administration significantly reduced bleeding time and hemorrhage and counteracted thrombocytopenia in rats subjected to tail amputation with or without anticoagulant treatment (heparin or warfarin). It also modulated the hemostatic effects induced by L-NAME and L-arginine, indicating a balancing role in NO-related hemostatic mechanisms.","whyItMatters":"Understanding how BPC 157 modulates bleeding and platelet function under anticoagulant conditions could lead to new treatments for managing bleeding complications and improving hemostasis in clinical settings.","specificNumbers":"","methodology":"Rats underwent tail amputation and were treated with intravenous heparin or oral warfarin to induce anticoagulation. They received BPC 157, L-NAME (a nitric oxide synthase blocker), L-arginine (a nitric oxide precursor), or combinations thereof. Bleeding time, hemorrhage, and platelet counts were measured to assess hemostatic effects.","limitations":"The study was conducted in rats, which may limit direct applicability to humans. The study type and evidence strength were not specified, and detailed statistical analyses were not provided."},{"rthcId":"RPEP-02801","title":"Phenotypic changes in dorsal root ganglion and spinal cord in the collagen antibody-induced arthritis mouse model.","authors":"Su, Jie; Gao, Tianle; Shi, Tiejun; Xiang, Qiong; Xu, Xiaojun; Wiesenfeld-Hallin, Zsuzsanna; Hökfelt, Tomas; Svensson, Camilla I","year":2015,"journal":"The Journal of comparative neurology, 523(10), 1505-28","doi":"10.1002/cne.23749","pmid":"25631752","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The study found significant increases in the neuropeptide galanin, ATP-gated ion channel P2X3, and calcium channel subunit α2δ1 in dorsal root ganglia of arthritic mice both during peak inflammation and after inflammation resolved. Markers of nerve injury, activating transcription factor 3 and growth-associated protein 43, were also elevated, suggesting a combined inflammatory and neuropathic pain state.","whyItMatters":"Understanding the molecular changes in nerves caused by arthritis can help develop better treatments targeting persistent pain, which is a major problem for patients even after inflammation subsides.","specificNumbers":"","methodology":"Researchers used the collagen antibody-induced arthritis (CAIA) mouse model to induce arthritis and examined protein expression in dorsal root ganglia and spinal cord at peak inflammation (day 15) and after inflammation resolution (days 45-47). They measured levels of neuropeptides, ion channels, and nerve injury markers using protein analysis techniques.","limitations":"The study was conducted in a mouse model, which may not fully replicate human arthritis pain mechanisms. The exact functional consequences of the molecular changes were not directly tested."},{"rthcId":"RPEP-02802","title":"Autocrine hemokinin-1 functions as an endogenous adjuvant for IgE-mediated mast cell inflammatory responses.","authors":"Sumpter, Tina L; Ho, Chin H; Pleet, Anna R; Tkacheva, Olga A; Shufesky, William J; Rojas-Canales, Darling M; Morelli, Adrian E; Larregina, Adriana T","year":2015,"journal":"The Journal of allergy and clinical immunology, 135(4), 1019-1030.e8","doi":"10.1016/j.jaci.2014.07.036","pmid":"25201259","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Mast cells activated via the IgE receptor increase production of hemokinin-1, which acts in an autocrine manner through the neurokinin-1 receptor (NK1R) to enhance secretion of inflammatory cytokines TNF and IL-6. NK1R signaling is essential for the full development of mast cell-mediated allergic responses in vivo.","whyItMatters":"Understanding how hemokinin-1 enhances mast cell-driven allergic inflammation could lead to new therapeutic targets for treating allergic diseases by modulating this autocrine signaling pathway.","specificNumbers":"","methodology":"The study used bone marrow-derived mast cells from wild-type and genetically modified mice lacking NK1R or hemokinin-1 to investigate the role of NK1R signaling in mast cell activation. In vivo models of anaphylaxis and airway inflammation were employed to assess the physiological relevance of NK1R signaling in allergic responses.","limitations":"The study was conducted primarily in mouse models and in vitro mast cell cultures, which may not fully replicate human allergic disease complexity. The exact contribution of substance P was less clear."},{"rthcId":"RPEP-02803","title":"Impact of GLP-1 receptor agonists on blood pressure, heart rate and hypertension among patients with type 2 diabetes: A systematic review and network meta-analysis.","authors":"Sun, Feng; Wu, Shanshan; Guo, Shuxia; Yu, Kai; Yang, Zhirong; Li, Lishi; Zhang, Yuan; Quan, Xiaochi; Ji, Linong; Zhan, Siyan","year":2015,"journal":"Diabetes research and clinical practice, 110(1), 26-37","doi":"10.1016/j.diabres.2015.07.015","pmid":"26358202","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02804","title":"Antimicrobial activity of synthetic cationic peptides and lipopeptides derived from human lactoferricin against Pseudomonas aeruginosa planktonic cultures and biofilms.","authors":"Sánchez-Gómez, Susana; Ferrer-Espada, Raquel; Stewart, Philip S; Pitts, Betsey; Lohner, Karl; Martínez de Tejada, Guillermo","year":2015,"journal":"BMC microbiology, 15, 137","doi":"10.1186/s12866-015-0473-x","pmid":"26149536","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Synthetic peptides derived from human lactoferricin demonstrated potent bactericidal activity against Pseudomonas aeruginosa planktonic cells and biofilms. Acylation enhanced killing of planktonic bacteria but reduced anti-biofilm activity. Peptides LF11-215 and LF11-227 caused a 10,000-fold reduction in biofilm viability at 10x MIC with low cytotoxicity, and LF11-227 removed over 50% of biofilm mass.","whyItMatters":"Pseudomonas aeruginosa biofilms are highly resistant to antibiotics, posing treatment challenges. These peptides offer a new approach to effectively kill both free bacteria and biofilms, potentially improving infection control.","specificNumbers":"","methodology":"The study used microdilution assays to determine MIC and MBC against planktonic bacteria, time-kill studies to assess killing speed, and biofilm assays under static and dynamic flow conditions to evaluate anti-biofilm activity. Both non-acylated peptides and N-acylated lipopeptides were tested.","limitations":"The study did not specify clinical trial data or in vivo testing, and further optimization of peptide structure is needed to enhance anti-biofilm activity."},{"rthcId":"RPEP-02805","title":"Semax, an ACTH4-10 peptide analog with high affinity for copper(II) ion and protective ability against metal induced cell toxicity.","authors":"Tabbì, Giovanni; Magrì, Antonio; Giuffrida, Alessandro; Lanza, Valeria; Pappalardo, Giuseppe; Naletova, Irina; Nicoletti, Vincenzo Giuseppe; Attanasio, Francesco; Rizzarelli, Enrico","year":2015,"journal":"Journal of inorganic biochemistry, 142, 39-46","doi":"10.1016/j.jinorgbio.2014.09.008","pmid":"25310602","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semax (Met-Glu-His-Phe-Pro-Gly-Pro), an ACTH4-10 analog with a C-terminal Pro-Gly-Pro extension, demonstrated:\n\n- Formation of three distinct copper(II) complex species\n- At pH 5 and above, the predominant species [CuLH-2]2- features 4-nitrogen planar coordination around copper\n- Two minor species [CuL] and [CuLH-1]- coexist at pH 3.6-5\n- Significant reduction of copper-induced cytotoxicity in:\n  - SH-SY5Y neuroblastoma cells (brain neuron model)\n  - RBE4 endothelial cells (blood-brain barrier model)\n- Protection assessed by MTT cell viability assay\n\nThis reveals that Semax’s neuroprotective activity may partly operate through metal ion chelation rather than solely through receptor-mediated signaling.","whyItMatters":"Metal ion dysregulation — particularly excess copper and zinc — is increasingly recognized as a driver of Alzheimer’s, Parkinson’s, and other neurodegenerative diseases. Semax is already approved in Russia for stroke and cognitive enhancement, and has a strong safety profile. This study reveals that Semax can serve double duty: providing cognitive benefits through its known neuroprotective signaling while also directly neutralizing toxic metal ions in the brain. This dual mechanism makes it a particularly attractive candidate for neurodegeneration research.","specificNumbers":"","methodology":"Copper(II) binding was characterized using equilibrium potentiometry and electron spin resonance (ESR) spectroscopy across a pH range. Complex speciation was determined as a function of pH. Neuroprotective activity was tested using MTT cell viability assays on SH-SY5Y neuroblastoma cells (modeling brain neurons) and RBE4 endothelial cells (modeling the blood-brain barrier), comparing copper toxicity in the presence and absence of Semax.","limitations":"This is an in vitro study using cell lines — protection in cultured cells may not translate to in vivo neuroprotection. The copper concentrations used in toxicity assays may not reflect physiological brain copper levels. The study focused on copper only; interactions with other relevant metals (zinc, iron) were not tested. Whether Semax reaches brain copper pools at sufficient concentrations after clinical administration is unknown. The study does not determine whether metal binding or receptor signaling is the primary mechanism of Semax’s known clinical benefits."},{"rthcId":"RPEP-02806","title":"Liraglutide improves pancreatic Beta cell mass and function in alloxan-induced diabetic mice.","authors":"Tamura, Kanako; Minami, Kohtaro; Kudo, Maya; Iemoto, Keisuke; Takahashi, Harumi; Seino, Susumu","year":2015,"journal":"PloS one, 10(5), e0126003","doi":"10.1371/journal.pone.0126003","pmid":"25938469","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02807","title":"VPAC2 (vasoactive intestinal peptide receptor type 2) receptor deficient mice develop exacerbated experimental autoimmune encephalomyelitis with increased Th1/Th17 and reduced Th2/Treg responses.","authors":"Tan, Yossan-Var; Abad, Catalina; Wang, Yuqi; Lopez, Robert; Waschek, James","year":2015,"journal":"Brain, behavior, and immunity, 44, 167-175","doi":"10.1016/j.bbi.2014.09.020","pmid":"25305591","tags":["neuropeptides","VIP"],"studyType":"Animal Study (Knockout Mouse Model)","evidenceStrength":"early-stage","keyFinding":"Mice lacking the VPAC2 receptor (which responds to the neuropeptides VIP and PACAP) developed much more severe autoimmune brain inflammation (EAE, the animal model for multiple sclerosis). Without VPAC2 signaling, the immune system shifted dramatically toward inflammation: pro-inflammatory Th1/Th17 responses were increased (TNF-α, IL-6, IFN-γ, IL-17), while protective Th2 and regulatory T cell (Treg) responses were reduced (IL-10, TGFβ, IL-4).\n\nMost strikingly, Treg cells — the immune system's brakes — were both fewer in number and functionally impaired in VPAC2-deficient mice. This demonstrates that the VPAC2 receptor is essential for maintaining the pool of Tregs that prevent autoimmune attacks.","whyItMatters":"Multiple sclerosis is driven by the same kind of autoimmune attack on the brain that this model represents. This study identifies a specific neuropeptide receptor (VPAC2) as a critical controller of the immune balance that prevents autoimmunity. Drugs that activate VPAC2 could potentially expand the Treg population and dampen the overactive immune responses that drive MS and other autoimmune diseases.","specificNumbers":"VPAC2 knockout vs wild type · enhanced clinical + histopathological EAE · increased TNF-α, IL-6, IFN-γ, IL-17 · decreased IL-10, TGFβ, IL-4 · reduced Treg abundance + proliferation + suppressive function","methodology":"Researchers used genetically engineered VPAC2-knockout mice and wild-type controls. EAE (experimental autoimmune encephalomyelitis) was induced using MOG35-55 peptide. They measured clinical disease severity, histopathology, cytokine levels (qRT-PCR), T cell populations in the CNS, lymph nodes, and thymus, and tested Treg suppressive function in vitro.","limitations":"Mouse EAE is a model for multiple sclerosis but doesn't perfectly replicate the human disease. Knockout studies show what happens when a receptor is completely absent from birth, which is different from blocking it pharmacologically in an adult. The study doesn't test whether activating VPAC2 could treat established disease. Specific sample sizes are not provided in the abstract."},{"rthcId":"RPEP-02808","title":"Efficacy and safety of liraglutide monotherapy compared with metformin in Japanese overweight/obese patients with type 2 diabetes.","authors":"Tanaka, Kumiko; Saisho, Yoshifumi; Kawai, Toshihide; Tanaka, Masami; Meguro, Shu; Irie, Junichiro; Imai, Takatoshi; Shigihara, Toshikatsu; Morimoto, Jiro; Yajima, Ken; Atsumi, Yoshihito; Takei, Izumi; Itoh, Hiroshi","year":2015,"journal":"Endocrine journal, 62(5), 399-409","doi":"10.1507/endocrj.EJ14-0602","pmid":"25739726","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02809","title":"BMP7-Based Functionalized Self-Assembling Peptides for Nucleus Pulposus Tissue Engineering.","authors":"Tao, Hui; Wu, Yaohong; Li, Haifeng; Wang, Chaofeng; Zhang, Yan; Li, Chao; Wen, Tianyong; Wang, Xiumei; He, Qing; Wang, Deli; Ruan, Dike","year":2015,"journal":"ACS applied materials & interfaces, 7(31), 17076-87","doi":"10.1021/acsami.5b03605","pmid":"26197234","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The functionalized peptide scaffold RAD-KPS significantly enhanced proliferation, migration, and extracellular matrix secretion (collagen II, aggrecan, sox-9) of human degenerated nucleus pulposus cells in vitro and degraded safely in vivo without causing inflammation, indicating its potential for nucleus pulposus tissue engineering.","whyItMatters":"This study introduces a new biomaterial scaffold that could improve treatments for intervertebral disc degeneration by promoting cell growth and matrix production, potentially leading to better spinal disc regeneration therapies.","specificNumbers":"","methodology":"Three BMP7-derived peptides were conjugated to the self-assembling peptide RADA16-I to form functionalized peptides (RAD-SNV, RAD-KPS, RAD-KAI). These were mixed with RADA16-I to create hydrogels, which were tested for bioactivity on human degenerated nucleus pulposus cells in vitro. The most effective scaffold was further evaluated for in vivo degradation and tissue response via subcutaneous injection in animal models.","limitations":"The study's evidence strength and clinical applicability remain unclear due to unknown study type and limited in vivo testing restricted to subcutaneous injection rather than direct spinal disc implantation."},{"rthcId":"RPEP-02810","title":"Reduction of soluble CD163, substance P, programmed death 1 and inflammatory markers: phase 1B trial of aprepitant in HIV-1-infected adults.","authors":"Tebas, Pablo; Spitsin, Sergei; Barrett, Jeffrey S; Tuluc, Florin; Elci, Okan; Korelitz, James J; Wagner, Wayne; Winters, Angela; Kim, Deborah; Catalano, Renae; Evans, Dwight L; Douglas, Steven D","year":2015,"journal":"AIDS (London, England), 29(8), 931-9","doi":"10.1097/QAD.0000000000000638","pmid":"25915168","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Aprepitant treatment for two weeks significantly decreased the percentage of CD4+ T cells expressing programmed death 1, plasma substance P, and soluble CD163 levels, indicating reduced immune activation, but did not affect plasma HIV viral load or CD4+ T cell counts.","whyItMatters":"Reducing immune activation without affecting viral load could help manage HIV-related inflammation and its complications, offering a new therapeutic angle beyond direct antiviral effects.","specificNumbers":"","methodology":"A phase 1B randomized, placebo-controlled, double-blinded trial with 18 HIV-1-infected adults receiving either 375 mg oral aprepitant or placebo once daily for two weeks, followed by four weeks off treatment.","limitations":"Small sample size and short treatment duration limit the ability to detect antiviral effects or long-term benefits; higher doses may be needed to observe clinical impact."},{"rthcId":"RPEP-02811","title":"Improving the passive permeability of macrocyclic peptides: Balancing permeability with other physicochemical properties.","authors":"Thansandote, Praew; Harris, Robert M; Dexter, Hannah L; Simpson, Graham L; Pal, Sandeep; Upton, Richard J; Valko, Klara","year":2015,"journal":"Bioorganic & medicinal chemistry, 23(2), 322-7","doi":"10.1016/j.bmc.2014.11.034","pmid":"25533323","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Enhancing passive permeability of 6- and 7-mer macrocyclic peptides often compromises solubility and lipophilicity. Computational molecular dynamics can guide design to balance these properties, though predictive accuracy is limited.","whyItMatters":"Understanding how to balance permeability with other properties is crucial for developing cyclic peptides as effective drug candidates. This knowledge aids in designing peptides that can enter cells without losing desirable characteristics.","specificNumbers":"","methodology":"The study used molecular dynamics simulations to design and evaluate modifications on 6- and 7-mer cyclic peptides. Various methods were tested to improve passive permeability while monitoring changes in physicochemical properties.","limitations":"The study's predictive computational methods showed limitations and the exact experimental validation details and sample sizes were not reported, limiting assessment of robustness."},{"rthcId":"RPEP-02812","title":"Biased Agonism of Endogenous Opioid Peptides at the μ-Opioid Receptor.","authors":"Thompson, Georgina L; Lane, J Robert; Coudrat, Thomas; Sexton, Patrick M; Christopoulos, Arthur; Canals, Meritxell","year":2015,"journal":"Molecular pharmacology, 88(2), 335-46","doi":"10.1124/mol.115.098848","pmid":"26013541","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Endogenous opioid peptides such as α-neoendorphin, Met-enkephalin-Arg-Phe, and endomorphin-1 exhibit distinct biased agonism profiles at the μ-opioid receptor compared to the synthetic agonist DAMGO, indicating natural ligand-specific signaling biases.","whyItMatters":"Understanding natural biased agonism at the μ-opioid receptor can guide the design of new opioid drugs that target specific signaling pathways, potentially improving pain management and reducing adverse effects.","specificNumbers":"","methodology":"The study used a common cellular system to measure multiple signaling pathways activated by endogenous opioid peptides and the synthetic agonist DAMGO. Techniques included assays for G protein activation, cAMP inhibition, ERK1/2 phosphorylation, β-arrestin recruitment, and receptor trafficking, combined with a novel analytical method to quantify biased agonism.","limitations":"The study was conducted in vitro using a single cellular background, so it remains to be confirmed whether these biased signaling profiles translate to different physiological effects in living organisms."},{"rthcId":"RPEP-02813","title":"Ovarian hyperstimulation syndrome in the 21st century: the role of gonadotropin-releasing hormone agonist trigger and kisspeptin.","authors":"Thomsen, Lise; Humaidan, Peter","year":2015,"journal":"Current opinion in obstetrics & gynecology, 27(3), 210-4","doi":"10.1097/GCO.0000000000000170","pmid":"25811256","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02814","title":"Kisspeptin signalling and its roles in humans.","authors":"Tng, Eng Loon","year":2015,"journal":"Singapore medical journal, 56(12), 649-56","doi":"10.11622/smedj.2015183","pmid":"26702158","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02815","title":"Peptide therapeutics: targeting the undruggable space.","authors":"Tsomaia, Natia","year":2015,"journal":"European journal of medicinal chemistry, 94, 459-70","doi":"10.1016/j.ejmech.2015.01.014","pmid":"25591543","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review highlights recent technological and chemical advancements in peptide design that enable targeting of intracellular protein-protein interactions, a class of targets traditionally considered undruggable by small molecules or biologics.","whyItMatters":"This work is important because it outlines how peptides can overcome limitations of existing drugs, potentially leading to new treatments for diseases involving intracellular protein interactions.","specificNumbers":"","methodology":"This is a review article summarizing current research and technological progress in peptide therapeutics, focusing on chemical strategies such as stapling and macrocyclization to stabilize peptides for intracellular targeting.","limitations":"As a review, it does not present new experimental data and the evidence strength and clinical applicability of discussed approaches remain to be fully established."},{"rthcId":"RPEP-02816","title":"Comparison Review of Short-Acting and Long-Acting Glucagon-like Peptide-1 Receptor Agonists.","authors":"Uccellatore, Annachiara; Genovese, Stefano; Dicembrini, Ilaria; Mannucci, Edoardo; Ceriello, Antonio","year":2015,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 6(3), 239-56","doi":"10.1007/s13300-015-0127-x","pmid":"26271795","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02817","title":"Ileal brake activation: macronutrient-specific effects on eating behavior?","authors":"van Avesaat, M; Troost, F J; Ripken, D; Hendriks, H F; Masclee, A A M","year":2015,"journal":"International journal of obesity (2005), 39(2), 235-43","doi":"10.1038/ijo.2014.112","pmid":"24957485","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Ileal infusion of lipid, casein (protein), and sucrose (carbohydrate) significantly reduced subsequent food intake compared to saline control. This reduction was accompanied by increased secretion of cholecystokinin and peptide YY, hormones involved in satiety, and a trend toward delayed gastric emptying and intestinal transit.","whyItMatters":"Understanding how different macronutrients activate the ileal brake can help develop dietary or therapeutic strategies to control appetite and manage obesity by targeting gut hormone pathways.","specificNumbers":"","methodology":"A randomized, single-blind, crossover study was conducted with 13 healthy adults who received ileal infusions of saline (control), safflower oil, low- and high-dose casein, and low- and high-dose sucrose. Food intake was measured during an ad libitum meal following infusion, along with blood sampling for gut hormones and questionnaires on hunger and satiety.","limitations":"The small sample size of 13 healthy young adults limits generalizability. The study was single-blind and did not report long-term effects or clinical outcomes."},{"rthcId":"RPEP-02818","title":"Intraduodenal infusion of a combination of tastants decreases food intake in humans.","authors":"van Avesaat, Mark; Troost, Freddy J; Ripken, Dina; Peters, Jelmer; Hendriks, Henk Fj; Masclee, Ad Am","year":2015,"journal":"The American journal of clinical nutrition, 102(4), 729-35","doi":"10.3945/ajcn.115.113266","pmid":"26289437","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Intraduodenal infusion of a combination of bitter, sweet, and umami tastants significantly decreased food intake and hunger scores compared to placebo, without altering plasma levels of gut peptides cholecystokinin, GLP-1, or PYY.","whyItMatters":"Understanding how taste receptors in the gut influence hunger and food intake could lead to new strategies for appetite control and obesity treatment without relying on changes in gut hormone levels.","specificNumbers":"","methodology":"A double-blind, randomized, placebo-controlled crossover study with 15 healthy volunteers was conducted. Participants received intraduodenal infusions of individual tastants, their combination, or placebo via nasoduodenal catheter after a standardized breakfast. Food intake was measured during an ad libitum meal, and blood samples were collected to analyze gut peptide levels.","limitations":"The small sample size limits generalizability, and the study did not explore long-term effects or mechanisms beyond gut peptide measurements."},{"rthcId":"RPEP-02819","title":"Blunted suppression of acyl-ghrelin in response to fructose ingestion in obese adolescents: the role of insulin resistance.","authors":"Van Name, Michelle; Giannini, Cosimo; Santoro, Nicola; Jastreboff, Ania M; Kubat, Jessica; Li, Fangyong; Kursawe, Romy; Savoye, Mary; Duran, Elvira; Dziura, James; Sinha, Rajita; Sherwin, Robert S; Cline, Gary; Caprio, Sonia","year":2015,"journal":"Obesity (Silver Spring, Md.), 23(3), 653-61","doi":"10.1002/oby.21019","pmid":"25645909","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In a double-blind crossover study of 41 adolescents (14 lean, 12 obese insulin-sensitive, 15 obese insulin-resistant):\n\nBaseline: acyl-ghrelin was highest in lean and lowest in obese insulin-resistant (OIR) (P=0.02)\n\nAfter glucose: ghrelin suppression was similar in lean and obese insulin-sensitive (OIS) but significantly lower in OIR (P=0.03 vs lean)\n\nAfter fructose: ghrelin suppression differences were more pronounced — lean vs OIS P=0.008, lean vs OIR P<0.001. OIS teens became significantly hungrier after fructose (P=0.015)\n\nPYY: not significantly different at baseline, varied minimally after glucose, but rose after fructose across groups\n\nThe pattern reveals a progressive impairment: OIS shows fructose-specific ghrelin suppression failure, while OIR shows failure with both sugars.","whyItMatters":"Fructose consumption has risen dramatically alongside obesity rates, particularly through high-fructose corn syrup in processed foods and sugary drinks. This study provides a mechanistic link: fructose specifically fails to suppress ghrelin in obese youth, meaning it doesn't turn off hunger the way glucose does. This could explain why fructose-heavy diets promote overconsumption. The progressive nature of the impairment — from fructose-specific in early obesity to both sugars in insulin resistance — suggests a worsening spiral that drives further weight gain.","specificNumbers":"","methodology":"Forty-one adolescents were divided into three groups: lean (n=14), obese insulin-sensitive (OIS, n=12), and obese insulin-resistant (OIR, n=15). In a double-blind, crossover design, subjects drank 75g of glucose or fructose in random order on separate visits. Blood samples were collected every 10 minutes for 60 minutes to measure acyl-ghrelin (the active form of the hunger hormone) and PYY (a satiety peptide). Subjective hunger was also assessed.","limitations":"The sample size is modest (41 total, 12-15 per group), limiting statistical power for subgroup analyses. The 60-minute observation window is short and may not capture the full hormonal response. The study used pure sugar solutions rather than mixed meals, which doesn't reflect real-world eating. Adolescent findings may not generalize to adults. The crossover design is a strength but carryover effects cannot be entirely excluded. Causation cannot be established — blunted ghrelin responses could be a consequence rather than a cause of obesity."},{"rthcId":"RPEP-02820","title":"Reciprocal Regulation of Substance P and IL-12/IL-23 and the Associated Cytokines, IFNγ/IL-17: A Perspective on the Relevance of This Interaction to Multiple Sclerosis.","authors":"Vilisaar, Janek; Kawabe, Kiyokazu; Braitch, Manjit; Aram, Jehan; Furtun, Yasemin; Fahey, Angela J; Chopra, Mark; Tanasescu, Radu; Tighe, Patrick J; Gran, Bruno; Pothoulakis, Charalabos; Constantinescu, Cris S","year":2015,"journal":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology, 10(3), 457-67","doi":"10.1007/s11481-015-9589-x","pmid":"25690155","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Treatment with substance P significantly increased expression of IL-12/IL-23 cytokine subunits in human peripheral blood mononuclear cells. IL-23 upregulated substance P and its receptor expression in T cells, suggesting a reciprocal regulatory mechanism that promotes proinflammatory Th1 and Th17 cell activity relevant to multiple sclerosis pathology.","whyItMatters":"Understanding how substance P regulates inflammatory cytokines helps clarify its role in autoimmune diseases like multiple sclerosis and highlights it as a potential therapeutic target to reduce harmful brain inflammation.","specificNumbers":"","methodology":"The study used quantitative real-time PCR, flow cytometry, ELISA, and promoter analysis on peripheral blood mononuclear cells and primary T cells from healthy volunteers, as well as Jurkat cell lines, to measure cytokine and receptor expression after substance P and cytokine stimulation.","limitations":"The study was conducted in vitro using cells from healthy donors and cell lines, which may not fully replicate the complex environment of multiple sclerosis in patients. The study type and evidence strength were not specified."},{"rthcId":"RPEP-02821","title":"The wasting continuum in heart failure: from sarcopenia to cachexia.","authors":"von Haehling, Stephan","year":2015,"journal":"The Proceedings of the Nutrition Society, 74(4), 367-77","doi":"10.1017/S0029665115002438","pmid":"26264581","tags":[],"studyType":"review","evidenceStrength":"moderate","keyFinding":"In heart failure patients, muscle wasting (sarcopenia) affects roughly 20% and full-body wasting (cachexia) affects under 10% of ambulatory patients. The review establishes a 'wasting continuum' where skeletal muscle is lost before fat tissue — meaning sarcopenia can be an early warning sign that cachexia is coming.\n\nMultiple peptide-based therapies show potential to halt this wasting process: ghrelin and its analogs stimulate appetite and preserve muscle, growth hormone and testosterone promote anabolism, and myostatin antibodies block the signals that tell muscle to break down. Exercise training, essential amino acids, and electrical muscle stimulation are also discussed as complementary approaches.","whyItMatters":"Muscle wasting in heart failure is a major cause of disability and death, yet it's often detected too late. This review frames sarcopenia as the treatable early stage of a continuum that leads to irreversible cachexia. The peptide therapies discussed — particularly ghrelin, ghrelin receptor agonists, and myostatin antibodies — represent a new generation of interventions that could stop wasting before it becomes catastrophic. Identifying and treating sarcopenia early in heart failure could fundamentally change patient outcomes.","specificNumbers":"~20% sarcopenia prevalence · <10% cachexia prevalence · muscle lost before fat · ghrelin, GH, testosterone, myostatin antibodies reviewed · exercise, amino acids, electrical stimulation also discussed","methodology":"Narrative review examining the pathophysiology of the sarcopenia-to-cachexia continuum in heart failure. Covers molecular mechanisms of muscle and fat wasting, discusses diagnostic criteria, and reviews potential therapeutic approaches including peptide-based, hormonal, nutritional, and physical interventions.","limitations":"Narrative review without systematic methodology or new data. The evidence for most discussed therapies comes from small trials or preclinical studies. No head-to-head comparisons between the various therapeutic approaches. The optimal timing and combination of interventions for the wasting continuum have not been established. Published in 2015 — newer data on some therapies (particularly myostatin antibodies) has since emerged."},{"rthcId":"RPEP-02822","title":"Endostatin's emerging roles in angiogenesis, lymphangiogenesis, disease, and clinical applications.","authors":"Walia, Amit; Yang, Jessica F; Huang, Yu-Hui; Rosenblatt, Mark I; Chang, Jin-Hong; Azar, Dimitri T","year":2015,"journal":"Biochimica et biophysica acta, 1850(12), 2422-38","doi":"10.1016/j.bbagen.2015.09.007","pmid":"26367079","tags":["anti-angiogenic-peptides","endostatin"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Endostatin — a 20-kDa peptide fragment naturally derived from type XVIII collagen — is one of the most potent known inhibitors of angiogenesis (new blood vessel formation). This review synthesizes a decade of research showing that endostatin works through multiple mechanisms: it binds to several different receptors, inhibits both blood vessel and lymphatic vessel growth, and can suppress cancer metastasis. The paper highlights endostatin's emerging role as both a disease biomarker (abnormal levels correlate with various diseases) and a potential therapeutic agent, particularly in short peptide form.","whyItMatters":"Tumors need blood vessels to grow and spread. Endostatin was initially hyped as a potential cancer cure, and while reality proved more complex, this review shows it remains a highly relevant molecule. Its dual potential as a biomarker for disease states and as a therapeutic peptide keeps it firmly in the research pipeline. Understanding endostatin's multiple mechanisms could lead to more effective anti-cancer combination therapies.","specificNumbers":"20-kDa peptide fragment · Derived from type XVIII collagen · Multiple receptor targets · Inhibits both angiogenesis and lymphangiogenesis","methodology":"This is a comprehensive review paper synthesizing published research on endostatin's biology, mechanisms of action, and clinical applications. The authors reviewed studies spanning endostatin's endogenous production, receptor binding, anti-angiogenic and anti-lymphangiogenic effects, cancer metastasis inhibition, and emerging clinical uses.","limitations":"As a review paper, this study doesn't present new experimental data. The clinical translation of endostatin has been slower than initially hoped, and the complexity of its multiple mechanisms makes it challenging to predict therapeutic outcomes. Some of the clinical applications discussed were still emerging at the time of publication."},{"rthcId":"RPEP-02823","title":"Exploring experimental and computational markers of cyclic peptides: Charting islands of permeability.","authors":"Wang, Conan K; Northfield, Susan E; Swedberg, Joakim E; Colless, Barbara; Chaousis, Stephanie; Price, David A; Liras, Spiros; Craik, David J","year":2015,"journal":"European journal of medicinal chemistry, 97, 202-13","doi":"10.1016/j.ejmech.2015.04.049","pmid":"25974856","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Cyclic peptides with high lipophilicity and low solvent hydrogen bonding interactions exhibit significantly higher membrane permeability, while those with low lipophilicity or many solvent interactions show low permeability. Molecular dynamics simulations support these findings by providing structural insights into peptide conformations related to permeability.","whyItMatters":"Understanding the factors that govern peptide permeability is crucial for developing orally bioavailable peptide drugs, which could improve treatment options by enabling easier administration.","specificNumbers":"","methodology":"The study synthesized 62 cyclic hexapeptides and measured their permeability using in vitro Caco-2 and PAMPA assays. Peptide conformations were characterized through chromatography and nuclear magnetic resonance spectroscopy, and molecular dynamics simulations were performed to model peptide behavior in solvent.","limitations":"The study is limited to cyclic hexapeptides and in vitro permeability assays, which may not fully predict in vivo absorption or apply to larger or structurally different peptides."},{"rthcId":"RPEP-02824","title":"Analysis of the ability of pramlintide to inhibit amyloid formation by human islet amyloid polypeptide reveals a balance between optimal recognition and reduced amyloidogenicity.","authors":"Wang, Hui; Ridgway, Zachary; Cao, Ping; Ruzsicska, Bela; Raleigh, Daniel P","year":2015,"journal":"Biochemistry, 54(44), 6704-11","doi":"10.1021/acs.biochem.5b00567","pmid":"26407043","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Rat IAPP (rIAPP) differs from human IAPP at six positions and is a natural amyloid inhibitor — a 'β-breaker' that combines a recognition element with structural features that prevent β-sheet formation. Pramlintide was engineered by introducing rIAPP's three proline substitutions into human IAPP, making it more human-like than rIAPP while still unable to form amyloid.\n\nComparison of rIAPP, pramlintide, and designed hIAPP analogues revealed that effective peptide-based amyloid inhibitors require a balance: too much similarity to hIAPP risks co-aggregation, while too many disrupting substitutions reduce the ability to recognize and bind the target. Pramlintide represents a well-calibrated compromise between these competing requirements.","whyItMatters":"Islet amyloid deposits contribute to beta cell loss in type 2 diabetes, worsening the disease over time. While pramlintide is already approved as a diabetes drug for glucose control, understanding exactly how it prevents amyloid formation opens the door to designing even more effective amyloid inhibitors — not just for diabetes but potentially for other amyloid diseases like Alzheimer's and Parkinson's, which involve similar misfolding mechanisms.","specificNumbers":"","methodology":"Biochemical analysis comparing the amyloid inhibitory activity of rat IAPP, pramlintide, and a set of designed human IAPP analogues with varying degrees of sequence modification. Amyloid formation kinetics and inhibition were assessed using standard biophysical assays to elucidate the structural features required for effective peptide-based amyloid inhibition.","limitations":"This is an in vitro biochemical study — the amyloid inhibition was measured in test tubes, not in living cells or animals. Whether the relative inhibitory potencies observed translate to differences in clinical effectiveness is unknown. The study examined amyloid formation inhibition but not other potential therapeutic mechanisms of pramlintide (such as its hormonal effects on glucose regulation)."},{"rthcId":"RPEP-02825","title":"Oxidative stress and substance P mediate psychological stress-induced autophagy and delay of hair growth in mice.","authors":"Wang, Lei; Guo, Ling-Ling; Wang, Lin-Hui; Zhang, Guo-Xing; Shang, Jing; Murao, Koji; Chen, Deng-Feng; Fan, Xiang-Hua; Fu, Wen-Qing","year":2015,"journal":"Archives of dermatological research, 307(2), 171-81","doi":"10.1007/s00403-014-1521-3","pmid":"25501647","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Chronic psychological stress in mice delayed hair growth by prolonging the telogen (resting) phase and postponing the next growth phases. Stress increased oxidative damage markers (lipid peroxidation) while reducing protective antioxidant enzymes (SOD and GSH-Px) in skin tissue. It also elevated autophagy markers LC3-II and Beclin-1 in the skin. Blocking the substance P receptor with RP67580 restored antioxidant enzyme activity, reduced oxidative damage, lowered autophagy markers, and normalized the hair cycle. The antioxidant Tempol produced similar protective effects. This is the first evidence linking substance P, oxidative stress, and autophagy together in stress-induced hair growth disruption.","whyItMatters":"Stress-related hair loss is extremely common, but the biological mechanisms have been poorly understood. This study identifies a clear pathway: psychological stress triggers substance P release and oxidative stress, which activate autophagy in skin cells, disrupting the hair cycle. This opens up two potential treatment targets — blocking substance P receptors or reducing oxidative stress — that could lead to new approaches for stress-related hair loss.","specificNumbers":"","methodology":"Male C57BL mice were subjected to 18 days of chronic restraint stress (a standard psychological stress model). Some groups received either Tempol (a free radical scavenger/antioxidant) or RP67580 (a substance P NK1 receptor antagonist). Researchers then measured hair growth cycle stages, oxidative stress markers (lipid peroxidation, SOD, GSH-Px), and autophagy proteins (LC3-II, Beclin-1) using ELISA and Western blot analysis.","limitations":"This was an animal study in mice, so the results may not directly translate to human stress-related hair loss. The restraint stress model is an approximation of psychological stress. The specific molecular cascade connecting substance P, oxidative stress, and autophagy was not fully mapped. Sample size was not reported in the abstract."},{"rthcId":"RPEP-02826","title":"Substance P enhances microglial density in the substantia nigra through neurokinin-1 receptor/NADPH oxidase-mediated chemotaxis in mice.","authors":"Wang, Qingshan; Oyarzabal, Esteban; Wilson, Belinda; Qian, Li; Hong, Jau-Shyong","year":2015,"journal":"Clinical science (London, England : 1979), 129(8), 757-67","doi":"10.1042/CS20150008","pmid":"26223840","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Substance P-deficient mice (TAC1 knockout) had significantly reduced microglial density in the substantia nigra compared to wild-type mice, despite no difference in microglial proliferation rates. Substance P dose-dependently attracted microglia in trans-well migration assays. The chemotactic mechanism required both the NK1 receptor (NK1R) and NADPH oxidase (NOX2), connected by protein kinase Cδ (PKCδ). Genetic ablation or pharmacological inhibition of either NK1R or NOX2 attenuated substance P-induced microglial migration. High levels of substance P were detectable in the substantia nigra as early as postnatal day 1, with microglial density peaking around postnatal day 30.","whyItMatters":"The substantia nigra's high microglial density is thought to make it uniquely vulnerable to neuroinflammation, which is a major driver of dopamine neuron death in Parkinson's disease. By identifying substance P as a key factor attracting microglia to this region, the study reveals a potential therapeutic target. Blocking substance P signaling could theoretically reduce the inflammatory burden in the substantia nigra and slow Parkinson's disease progression.","specificNumbers":"","methodology":"Researchers quantified microglial density in wild-type and TAC1 knockout (substance P-deficient) mice from postnatal day 1 through day 30. In vitro trans-well culture systems tested substance P's chemotactic effects on microglia at different concentrations. Genetic knockout models and pharmacological inhibitors targeting NK1R and NOX2 were used to dissect the signaling pathway. PKCδ was identified as the coupling molecule between NK1R activation and NOX2 activation.","limitations":"The study was conducted in developing postnatal mice, so the findings may not directly apply to adult brains or human Parkinson's disease. Only microglial recruitment was examined — the functional consequences of altered microglial density (e.g., effects on dopamine neuron survival) were not tested. The in vitro chemotaxis assay, while informative, is simplified compared to the complex brain environment."},{"rthcId":"RPEP-02827","title":"High-protein breakfast promotes weight loss by suppressing subsequent food intake and regulating appetite hormones in obese Chinese adolescents.","authors":"Wang, Shaoyun; Yang, Lijuan; Lu, Juming; Mu, Yiming","year":2015,"journal":"Hormone research in paediatrics, 83(1), 19-25","doi":"10.1159/000362168","pmid":"24923232","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A high-protein breakfast containing eggs significantly reduced subsequent lunchtime food intake and body weight in obese Chinese adolescents, associated with increased anorexigenic hormones peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) and decreased hunger.","whyItMatters":"Understanding how high-protein breakfasts regulate appetite hormones can help develop effective dietary strategies for adolescent obesity management.","specificNumbers":"","methodology":"156 obese Chinese adolescents were randomly assigned to eat either an egg-based or steamed bread breakfast with equal calories. Food intake at lunch was measured 4 hours later, appetite hormones were assessed at multiple time points, and body weight was recorded. The tests were repeated after 3 months.","limitations":"The study design type is not specified, and evidence strength is unknown. Results may not generalize beyond obese Chinese adolescents."},{"rthcId":"RPEP-02828","title":"Substance P prevents 1-methyl-4-phenylpyridinium-induced cytotoxicity through inhibition of apoptosis via neurokinin-1 receptors in MES23.5 cells.","authors":"Wang, Shuang-Yan; Chen, Lei; Xue, Yan; Xia, Yu-Jun","year":2015,"journal":"Molecular medicine reports, 12(6), 8085-92","doi":"10.3892/mmr.2015.4464","pmid":"26497672","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Substance P (specifically the selective NK-1 agonist [Sar9, Met(O2)11]-SP) protected MES23.5 dopaminergic cells from MPP+-induced toxicity through multiple mechanisms:\n\n- Prevented MPP+-triggered apoptosis (programmed cell death)\n- Decreased MPP+-induced calcium (Ca2+) influx into cells\n- Reduced caspase-3 reactivity (a key enzyme in the cell death cascade)\n- Lowered reactive oxygen species (ROS) production\n- Preserved mitochondrial membrane potential (preventing mitochondrial collapse)\n- Inhibited phosphorylation of JNK and p38 MAP kinase (stress-activated signaling pathways)\n\nAll protective effects were abolished when the NK-1 receptor antagonist SR140333B was co-administered, confirming that substance P's neuroprotection is mediated specifically through NK-1 receptors.","whyItMatters":"Parkinson's disease currently has no treatments that stop or slow neuronal death — all existing drugs only manage symptoms. If substance P genuinely protects dopamine neurons, it could represent a neuroprotective strategy. The finding that the protection works through a specific receptor (NK-1) makes it potentially targetable with drugs, though the complexity is that NK-1 receptor antagonists are being developed for other conditions, creating a therapeutic paradox.","specificNumbers":"","methodology":"MES23.5 dopaminergic cells (a hybrid cell line of rat mesencephalic neurons) were treated with MPP+ (1-methyl-4-phenylpyridinium) to induce Parkinson's-like toxicity. Cells were pre-treated with substance P ([Sar9, Met(O2)11]-SP) with or without the NK-1 receptor antagonist SR140333B. Researchers measured cell viability, DNA fragmentation, calcium influx, caspase-3 activity, reactive oxygen species levels, mitochondrial membrane potential, and phosphorylation of JNK and p38 MAPK signaling pathways.","limitations":"This is an in vitro study using a single cell line (MES23.5), which does not replicate the complex environment of the living brain with its multiple cell types, blood-brain barrier, and immune interactions. The MPP+ model, while widely used, represents only one mechanism of dopaminergic cell death in Parkinson's disease. Specific concentrations of substance P and MPP+ used are not detailed in the abstract. No dose-response relationship is described. The findings have not been validated in animal models of Parkinson's disease."},{"rthcId":"RPEP-02829","title":"Efficacy of thymosin α1 and interferon α for the treatment of severe acute pancreatitis in a rat model.","authors":"Wang, Xiaoqin; Zeng, Xiaoyan; Yang, Bo; Zhao, Shan; Chen, Wei; Guo, Xuan","year":2015,"journal":"Molecular medicine reports, 12(5), 6775-81","doi":"10.3892/mmr.2015.4277","pmid":"26330363","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 144 rats randomized to four groups, treatment with thymosin alpha-1 (26.7 µg/kg IV) after SAP induction produced significant improvements:\n\nSurvival: Mortality reduced from 50% (6/12) in untreated SAP to 25% (3/12) with TA1 treatment\n\nImmune function: Significantly increased CD3+, CD4+, and CD8+ T-cells and improved CD4+/CD8+ ratio compared to untreated SAP\n\nInflammatory markers: Significantly lower levels of AST, LDH, α-amylase, P-type amylase, lipase, procalcitonin, TNF-α, IL-4, IL-5, and IL-18 within the first 24 hours (all P<0.05)\n\nHistology: Significantly reduced pancreatic and lung tissue damage on histological scoring\n\nIFNα treatment (4.0×10⁵ U/kg) showed similar benefits, reducing mortality to 33.3% (4/12)","whyItMatters":"Severe acute pancreatitis kills approximately 20-30% of patients and has no specific pharmacological treatment beyond supportive care. The immune system plays a critical role — early hyperinflammation causes organ damage, while subsequent immunosuppression leads to infection and death. Thymosin alpha-1 addresses both problems: it modulates inflammation while boosting T-cell immunity. As an approved drug in some countries for hepatitis treatment, it could potentially be repurposed for pancreatitis relatively quickly.","specificNumbers":"","methodology":"One hundred forty-four Sprague-Dawley rats were randomly divided into four groups: control (saline), SAP (5% sodium taurocholate via cholangiopancreatic duct + saline IV), TA1-treated (SAP + 26.7 µg/kg TA1 IV), and IFNα-treated (SAP + 4.0×10⁵ U/kg IFNα IV). Blood was collected at 3, 12, and 24 hours post-surgery for T-cell subset analysis, enzyme markers, cytokines, and procalcitonin. Pancreatic and lung tissues were evaluated by H&E staining with histological scoring. Survival was tracked through the study period.","limitations":"This is a rat model of pancreatitis induced by sodium taurocholate, which mimics biliary pancreatitis but may not represent all causes of SAP in humans. The survival data came from subgroups of only 12 rats each, limiting statistical power for mortality comparisons. The 24-hour observation window for biomarkers is very short — longer-term effects are unknown. The mechanism by which TA1 modulates the immune response in pancreatitis is not fully elucidated. Translation to human clinical practice requires clinical trials."},{"rthcId":"RPEP-02830","title":"Extrinsic ghrelin in the paraventricular nucleus increases small intestinal motility in rats by activating central growth hormone secretagogue and enteric cholinergic receptors.","authors":"Wang, Yan; Chen, Fenrong; Shi, Haitao; Jiang, Jiong; Li, Hong; Qin, Bin; Li, Yong","year":2015,"journal":"Peptides, 74, 43-9","doi":"10.1016/j.peptides.2015.09.009","pmid":"26431788","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Ghrelin injected into the paraventricular nucleus (PVN) at doses of 0.03, 0.08, and 0.24 nM dose-dependently accelerated small intestinal transit (SIT) in rats. This effect was systematically dissected:\n\n- GHSR antagonist (D-Lys3-GHRP6, 1 nM) competitively inhibited ghrelin's excitatory effect on SIT and interdigestive myoelectric complex (IMC) activity\n- NPY neutralization in the PVN using anti-NPY immunoglobulin also diminished the excitatory effect on IMC\n- Peripheral muscarinic acetylcholine receptor blockade with intravenous atropine reduced ghrelin's gut motility effects\n- c-Fos immunohistochemistry showed ghrelin upregulated neuronal activation in the PVN, other central nuclei, and enteric nervous plexuses of the stomach, duodenum, and proximal colon — all dependent on central GHSR activation","whyItMatters":"Millions of people suffer from gut motility disorders like gastroparesis, irritable bowel syndrome, and post-operative ileus. Understanding the precise brain-gut signaling pathway that ghrelin uses to control intestinal movement could lead to more targeted therapies. This study maps out a complete signaling chain — from a specific brain nucleus through neuropeptide intermediaries to gut nerve endings — providing multiple potential intervention points for drug development.","specificNumbers":"","methodology":"Thirty-six male Sprague-Dawley rats were surgically fitted with duodenal catheters and PVN cannulas. Multiple experimental groups received: ghrelin at three doses (0.03, 0.08, 0.24 nM) into the PVN; GHSR antagonist D-Lys3-GHRP6 alone or before ghrelin; anti-NPY IgG into the PVN; or intravenous atropine. Small intestinal transit was measured via the catheter system. Interdigestive myoelectric complex recordings were obtained through implanted intestinal electrodes. Neuronal activation was mapped using c-Fos immunohistochemistry in brain regions and enteric nervous system plexuses.","limitations":"The study was conducted in anesthetized rats with surgically implanted cannulas and catheters, which is a highly artificial setting that may not reflect normal physiology. Direct PVN injection bypasses the normal routes by which ghrelin reaches the brain. Only male rats were used. The 36-rat sample was split across multiple experimental groups, resulting in small group sizes. The study examined acute effects only — chronic ghrelin exposure might produce different results due to receptor desensitization."},{"rthcId":"RPEP-02831","title":"Clinical and neural effects of six-week administration of oxytocin on core symptoms of autism.","authors":"Watanabe, Takamitsu; Kuroda, Miho; Kuwabara, Hitoshi; Aoki, Yuta; Iwashiro, Norichika; Tatsunobu, Natsubori; Takao, Hidemasa; Nippashi, Yasumasa; Kawakubo, Yuki; Kunimatsu, Akira; Kasai, Kiyoto; Yamasue, Hidenori","year":2015,"journal":"Brain : a journal of neurology, 138(Pt 11), 3400-12","doi":"10.1093/brain/awv249","pmid":"26336909","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Six-week intranasal oxytocin administration significantly reduced core social reciprocity symptoms in high-functioning adult males with autism (P = 0.034, PFDR < 0.05, Cohen's d = 0.78). This clinical improvement correlated with enhanced resting-state functional connectivity between the anterior cingulate cortex and dorso-medial prefrontal cortex (rho = -0.60, P = 0.011). Behavioral and neural responses during social judgment tasks also improved significantly.","whyItMatters":"This study provides evidence that long-term oxytocin administration can improve core social symptoms of autism and modulate brain networks involved in social cognition, supporting its potential as a therapeutic option.","specificNumbers":"","methodology":"A randomized, double-blind, placebo-controlled, crossover trial was conducted with 20 high-functioning adult males with autism; 18 completed the study. Participants received six weeks of intranasal oxytocin or placebo, with clinical assessments and functional MRI scans performed before and after treatment.","limitations":"The small sample size and inclusion of only high-functioning adult males limit generalizability. The study duration was relatively short, and effect sizes did not exceed those from single-dose studies, indicating the need for optimized dosing regimens."},{"rthcId":"RPEP-02832","title":"Gastrointestinal peptides and itch sensation.","authors":"Weber, H Christian","year":2015,"journal":"Current opinion in endocrinology, diabetes, and obesity, 22(1), 29-33","doi":"10.1097/MED.0000000000000122","pmid":"25485517","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Gastrin-releasing peptide (GRP) and its receptor (GRPR) are key regulators in spinal cord itch pathways and may maintain chronic itch sensation. Other neuropeptides such as neuromedin B and substance P modulate itch signaling cooperatively or inhibitively. Neurokinin 1 receptor antagonists show potential benefits in treating chronic itch based on small clinical studies.","whyItMatters":"Identifying peptides involved in itch signaling could lead to targeted therapies for chronic itch, a condition with limited treatment options that significantly impacts quality of life.","specificNumbers":"","methodology":"This is a review article summarizing recent advances in research on gastrointestinal peptides related to itch sensation, focusing on molecular pathways and clinical implications.","limitations":"The evidence is based on a review of existing studies, some of which are small clinical trials; the overall strength and clinical applicability remain to be fully established."},{"rthcId":"RPEP-02833","title":"Ghrelin signaling in the ventral tegmental area mediates both reward-based feeding and fasting-induced hyperphagia on high-fat diet.","authors":"Wei, X J; Sun, B; Chen, K; Lv, B; Luo, X; Yan, J Q","year":2015,"journal":"Neuroscience, 300, 53-62","doi":"10.1016/j.neuroscience.2015.05.001","pmid":"25967263","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Microinjection of ghrelin into the VTA dose-dependently increased reward-based feeding and fasting-induced hyperphagia on a high-fat diet in rats, resulting in significant 24-hour body weight gain. These effects were blocked by the ghrelin receptor antagonist D-Lys3-GHRP-6, demonstrating that ghrelin signaling in the VTA mediates both hedonic and hunger-driven overeating.","whyItMatters":"Understanding how ghrelin in the brain's reward centers drives overeating of high-fat foods can help develop targeted treatments for obesity and related eating disorders by modulating this pathway.","specificNumbers":"","methodology":"Rats were conditioned to restricted feeding schedules and given intra-VTA microinjections of varying doses of ghrelin or a ghrelin receptor antagonist. Food intake of high-fat diet and body weight changes were measured under sated and fasting conditions to assess ghrelin's effects on feeding behavior.","limitations":"The study was conducted in rats, so results may not fully translate to humans. The exact neural circuits downstream of VTA ghrelin signaling were not explored in detail."},{"rthcId":"RPEP-02834","title":"Substance P and the regulation of inflammation in infections and inflammatory bowel disease.","authors":"Weinstock, J V","year":2015,"journal":"Acta physiologica (Oxford, England), 213(2), 453-61","doi":"10.1111/apha.12428","pmid":"25424746","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Substance P and hemokinin-1, produced by lymphocytes and macrophages, act through the neurokinin-1 receptor to enhance proinflammatory cytokine production, amplifying inflammation in infections and inflammatory bowel disease. Their synthesis and receptor expression are regulated by cytokines such as IL12, IL23, IL18, TNFα, IL10, and TGFβ, indicating a complex immune regulatory circuit.","whyItMatters":"Understanding how Substance P regulates inflammation can help develop new treatments targeting immune responses in infections and inflammatory bowel diseases, potentially improving patient outcomes.","specificNumbers":"","methodology":"This study reviews existing research on the production and regulation of Substance P and hemokinin-1 by immune cells, their receptor interactions, and their role in inflammation during infections and inflammatory bowel disease, including evidence from animal models.","limitations":"The study is a review and does not provide new experimental data; some cytokines regulating hemokinin-1 production remain unidentified, and the exact mechanisms in humans need further research."},{"rthcId":"RPEP-02835","title":"Ghrelin partially protects against cisplatin-induced male murine gonadal toxicity in a GHSR-1a-dependent manner.","authors":"Whirledge, Shannon D; Garcia, Jose M; Smith, Roy G; Lamb, Dolores J","year":2015,"journal":"Biology of reproduction, 92(3), 76","doi":"10.1095/biolreprod.114.123570","pmid":"25631345","tags":[],"studyType":"animal study","evidenceStrength":"low","keyFinding":"The hunger hormone peptide ghrelin partially protected against cisplatin-induced testicular damage and cachexia (muscle wasting) in male mice. When given alongside cisplatin chemotherapy, ghrelin significantly increased body, testicular, and epididymal weights while reducing testicular cell death. The widespread damage to sperm-producing tissue (seminiferous epithelium) caused by cisplatin was less severe with ghrelin co-treatment. Critically, these protective effects were absent in mice lacking the ghrelin receptor (GHSR-1a), confirming the effects are specifically mediated through this receptor and not off-target.","whyItMatters":"Cisplatin is one of the most effective and widely used chemotherapy drugs, but high cumulative doses can cause permanent infertility in male cancer patients through testicular damage. Currently, sperm banking before treatment is the main fertility preservation option. If ghrelin or a stable GHSR agonist could protect testicular tissue during chemotherapy, it would represent a fundamentally different approach — preserving natural fertility rather than relying on cryopreservation. This is especially important for young cancer patients facing a lifetime of potential infertility.","specificNumbers":"2 treatment cycles (9 and 18 days) · GHSR-1a dependent protection · Body, testicular, and epididymal weights all improved · Testicular cell death reduced","methodology":"Adult male C57Bl/6 mice received intraperitoneal injections of vehicle, ghrelin, cisplatin alone, or cisplatin plus ghrelin in cycles of 9 or 18 days. Body weight was measured daily. At study end, testicular and epididymal weights, sperm density and motility, testicular histology, and testicular cell death were analyzed. The role of the ghrelin receptor was confirmed using GHSR knockout mice.","limitations":"This is a mouse study — cisplatin dosing, ghrelin pharmacokinetics, and testicular biology differ between mice and humans. The study doesn't address whether ghrelin protection might interfere with cisplatin's anticancer efficacy. Specific sperm count and motility data are mentioned but not quantified in the abstract. Long-term reproductive outcomes (actual fertility/offspring) were not assessed. The optimal timing, dose, and duration of ghrelin co-administration for clinical translation remain unknown."},{"rthcId":"RPEP-02836","title":"The Brain Hepatocyte Growth Factor/c-Met Receptor System: A New Target for the Treatment of Alzheimer's Disease.","authors":"Wright, John W; Harding, Joseph W","year":2015,"journal":"Journal of Alzheimer's disease : JAD, 45(4), 985-1000","doi":"10.3233/JAD-142814","pmid":"25649658","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02837","title":"The development of small molecule angiotensin IV analogs to treat Alzheimer's and Parkinson's diseases.","authors":"Wright, John W; Kawas, Leen H; Harding, Joseph W","year":2015,"journal":"Progress in neurobiology, 125, 26-46","doi":"10.1016/j.pneurobio.2014.11.004","pmid":"25455861","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02838","title":"Immunogenicity in Swine of Orally Administered Recombinant Lactobacillus plantarum Expressing Classical Swine Fever Virus E2 Protein in Conjunction with Thymosin α-1 as an Adjuvant.","authors":"Xu, Yi-Gang; Guan, Xue-Ting; Liu, Zhong-Mei; Tian, Chang-Yong; Cui, Li-Chun","year":2015,"journal":"Applied and environmental microbiology, 81(11), 3745-52","doi":"10.1128/AEM.00127-15","pmid":"25819954","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Recombinant Lactobacillus plantarum expressing the CSFV E2 protein, especially when combined with thymosin α-1 as an adjuvant, induced significant mucosal IgA, serum IgG, and cytotoxic T lymphocyte responses in pigs, indicating enhanced immunogenicity and potential protective immunity against classical swine fever virus.","whyItMatters":"This research offers a promising oral vaccine strategy that could improve swine health and reduce economic losses from classical swine fever by enhancing immune protection using a peptide adjuvant.","specificNumbers":"","methodology":"The study genetically engineered Lactobacillus plantarum strains to express the CSFV E2 protein alone or with thymosin α-1. These strains were orally administered to pigs, and immune responses including IgA, IgG, and CTL activity were measured to evaluate vaccine efficacy.","limitations":"The study type and evidence strength are not specified, and long-term protective efficacy and safety were not detailed, limiting conclusions on vaccine performance in diverse field conditions."},{"rthcId":"RPEP-02839","title":"Soluble dietary fiber (Fibersol-2) decreased hunger and increased satiety hormones in humans when ingested with a meal.","authors":"Ye, Zhong; Arumugam, Visalakshi; Haugabrooks, Esther; Williamson, Patricia; Hendrich, Suzanne","year":2015,"journal":"Nutrition research (New York, N.Y.), 35(5), 393-400","doi":"10.1016/j.nutres.2015.03.004","pmid":"25823991","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Ingesting 10 g of Fibersol-2 with a meal significantly delayed hunger and increased satiety for 1.5 to 2 hours post-meal. This dose also significantly elevated plasma levels of satiety hormones peptide YY and glucagon-like peptide-1 compared to 0 or 5 g doses.","whyItMatters":"Understanding how dietary fibers like Fibersol-2 influence hunger and satiety hormones can help develop nutritional strategies to control appetite and support weight management.","specificNumbers":"","methodology":"A randomized, double-blind, placebo-controlled crossover study was conducted with 19 healthy adults who consumed a standardized meal with tea containing 0, 5, or 10 g Fibersol-2. Subjective appetite was measured every 30 minutes using a visual analog scale, and blood samples were taken at multiple time points up to 4 hours post-meal to measure satiety hormones via ELISA.","limitations":"The study had a small sample size of 19 participants and short-term measurements limited to 4 hours post-meal. Long-term effects and impacts in diverse populations remain unclear."},{"rthcId":"RPEP-02840","title":"Degradation and Stabilization of Peptide Hormones in Human Blood Specimens.","authors":"Yi, Jizu; Warunek, David; Craft, David","year":2015,"journal":"PloS one, 10(7), e0134427","doi":"10.1371/journal.pone.0134427","pmid":"26222180","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02841","title":"Elevated plasma norepinephrine level and sick sinus syndrome in patients with lone atrial fibrillation.","authors":"Yoshida, Kentaro; Kaneshiro, Takashi; Ito, Yoko; Kimata, Akira; Koda, Naoya; Hiraya, Daigo; Baba, Masako; Misaki, Masako; Takeyasu, Noriyuki; Yamaguchi, Iwao; Aonuma, Kazutaka","year":2015,"journal":"Heart (British Cardiac Society), 101(14), 1133-8","doi":"10.1136/heartjnl-2014-307334","pmid":"25968056","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Plasma norepinephrine levels were significantly elevated in patients with atrial fibrillation who also had symptomatic sick sinus syndrome compared to those without. Norepinephrine was the only independent predictor of sick sinus syndrome among measured biomarkers.","whyItMatters":"Identifying norepinephrine as a marker linked to sick sinus syndrome may help in understanding autonomic nervous system involvement in heart rhythm disorders and guide future treatments.","specificNumbers":"","methodology":"The study analyzed blood samples from 137 patients undergoing catheter ablation for lone atrial fibrillation. Levels of norepinephrine, atrial natriuretic peptide, and brain natriuretic peptide were measured before the procedure and compared between patient groups.","limitations":"The study design and evidence strength were not specified, and causality cannot be established. The sample size, while moderate, may limit generalizability. Further studies are needed to clarify mechanisms."},{"rthcId":"RPEP-02842","title":"Thymosin α1 promotes the activation of myeloid-derived suppressor cells in a Lewis lung cancer model by upregulating Arginase 1.","authors":"Yuan, Chao; Zheng, Yisheng; Zhang, Bo; Shao, LiJuan; Liu, Yang; Tian, Tian; Gu, XiaoBin; Li, Xiangnan; Fan, KeXing","year":2015,"journal":"Biochemical and biophysical research communications, 464(1), 249-55","doi":"10.1016/j.bbrc.2015.06.132","pmid":"26111447","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Thymosin α1 treatment in a Lewis lung cancer model increases CD8(+) T cells but fails to inhibit tumor growth due to activation of myeloid-derived suppressor cells (MDSCs) with elevated Arginase 1 production via TLRs/MyD88 signaling. Blocking MyD88 signaling reduces ARG1 expression and restores Tα1’s anti-tumor efficacy.","whyItMatters":"These findings reveal a mechanism by which Tα1 can inadvertently suppress anti-tumor immunity, guiding improved immunotherapy strategies that combine Tα1 with inhibitors of MDSC activation.","specificNumbers":"","methodology":"The study used a Lewis lung cancer mouse model to analyze the effects of Tα1 treatment on immune cell populations and tumor growth. Molecular assays assessed Arginase 1 expression and the role of TLRs/MyD88 signaling in MDSC activation.","limitations":"The study was conducted in a mouse lung cancer model, which may not fully replicate human cancer biology. The exact clinical relevance and optimal combination therapies remain to be determined."},{"rthcId":"RPEP-02843","title":"Adaptive cardiovascular hormones in a spectrum of heart failure phenotypes.","authors":"Zabarovskaja, Stanislava; Hage, Camilla; Linde, Cecilia; Daubert, Jean-Claude; Donal, Erwan; Gabrielsen, Anders; Mellbin, Linda; Lund, Lars H","year":2015,"journal":"International journal of cardiology, 189, 6-11","doi":"10.1016/j.ijcard.2015.03.381","pmid":"25885866","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"NT-proBNP and MR-proANP levels were significantly elevated in heart failure patients, with higher levels in reduced ejection fraction (HFrEF) compared to preserved ejection fraction (HFpEF). Both peptides independently predicted survival free from heart transplantation or left ventricular assist device implantation. MR-proADM levels did not differ significantly between HFpEF and HFrEF and did not predict prognosis.","whyItMatters":"Understanding how these peptides vary with heart failure type and treatment can improve risk assessment and guide clinical management. It highlights NT-proBNP and MR-proANP as valuable biomarkers for prognosis in diverse heart failure phenotypes.","specificNumbers":"","methodology":"The study measured plasma levels of NT-proBNP, MR-proANP, and MR-proADM in 86 HFpEF patients, 49 HFrEF patients, 13 post-LVAD, and 22 post-heart transplant patients. Prognostic impact was assessed using Kaplan-Meier survival analysis and multivariable Cox regression adjusting for clinical factors.","limitations":"The study's observational design limits causal conclusions. The sample size for post-LVAD and post-transplant groups was small, which may affect generalizability. The study type and evidence strength were not specified."},{"rthcId":"RPEP-02844","title":"Multifunctional peptides derived from an egg yolk protein hydrolysate: isolation and characterization.","authors":"Zambrowicz, Aleksandra; Pokora, Marta; Setner, Bartosz; Dąbrowska, Anna; Szołtysik, Marek; Babij, Konrad; Szewczuk, Zbigniew; Trziszka, Tadeusz; Lubec, Gert; Chrzanowska, Józefa","year":2015,"journal":"Amino acids, 47(2), 369-80","doi":"10.1007/s00726-014-1869-x","pmid":"25408464","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02845","title":"Collagen peptide supplementation in combination with resistance training improves body composition and increases muscle strength in elderly sarcopenic men: a randomised controlled trial.","authors":"Zdzieblik, Denise; Oesser, Steffen; Baumstark, Manfred W; Gollhofer, Albert; König, Daniel","year":2015,"journal":"The British journal of nutrition, 114(8), 1237-45","doi":"10.1017/S0007114515002810","pmid":"26353786","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02846","title":"Sulfakinin is an important regulator of digestive processes in the migratory locust, Locusta migratoria.","authors":"Zels, Sven; Dillen, Senne; Crabbé, Katleen; Spit, Jornt; Nachman, Ronald J; Vanden Broeck, Jozef","year":2015,"journal":"Insect biochemistry and molecular biology, 61, 8-16","doi":"10.1016/j.ibmb.2015.03.008","pmid":"25846060","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Sulfakinin significantly reduces food intake and inhibits digestive enzyme secretion in the midgut and gastric caeca of Locusta migratoria. The sulfation of the tyrosine residue in sulfakinin is essential for these effects. Peptidomimetic analogs of sulfakinin partially mimic these inhibitory effects on digestive enzyme secretion.","whyItMatters":"Understanding how sulfakinin regulates digestion and feeding in insects can guide the development of novel pest control strategies and peptidomimetic compounds that target insect digestive processes.","specificNumbers":"","methodology":"The study involved injecting sulfakinin and its analogs into migratory locusts and measuring food intake, digestive enzyme secretion, absorbance, and proteolytic activity in the gut. The role of sulfation on tyrosine was assessed by comparing effects of sulfated versus non-sulfated peptides.","limitations":"The study does not specify the exact sample size or experimental controls, and the evidence strength is unknown. Effects were observed under experimental injection conditions, which may differ from natural peptide release dynamics."},{"rthcId":"RPEP-02847","title":"BPC 157 antagonized the general anaesthetic potency of thiopental and reduced prolongation of anaesthesia induced by L-NAME/thiopental combination.","authors":"Zemba, Mladen; Cilic, Andrea Zemba; Balenovic, Igor; Cilic, Matija; Radic, Bozo; Suran, Jelena; Drmic, Domagoj; Kokot, Antonio; Stambolija, Vasilije; Murselovic, Tamara; Holjevac, Jadranka Katancic; Uzun, Sandra; Djuzel, Viktor; Vlainic, Josipa; Seiwerth, Sven; Sikiric, Predrag","year":2015,"journal":"Inflammopharmacology, 23(6), 329-36","doi":"10.1007/s10787-015-0249-9","pmid":"26563892","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BPC 157 at doses of 10 ng/kg and 10 μg/kg significantly antagonized thiopental-induced anesthesia, shifting the dose-response curve to the right. L-NAME tripled anesthesia duration, but BPC 157 counteracted this prolongation, demonstrating modulation of nitric oxide-related mechanisms in anesthesia.","whyItMatters":"Understanding how BPC 157 modulates anesthesia through nitric oxide pathways could lead to improved control of anesthesia duration and recovery, potentially benefiting surgical and clinical practices involving peptide therapeutics.","specificNumbers":"","methodology":"Rats received intraperitoneal injections of thiopental at varying doses with or without BPC 157 administered prior to thiopental. Additional groups received nitric oxide synthase inhibitor L-NAME and precursor L-arginine alone or combined with BPC 157 to assess nitric oxide involvement in anesthesia duration.","limitations":"The study was conducted only in rats, limiting direct applicability to humans. The exact mechanisms of BPC 157's interaction with nitric oxide pathways require further elucidation."},{"rthcId":"RPEP-02848","title":"Anamorelin hydrochloride for the treatment of cancer-anorexia-cachexia in NSCLC.","authors":"Zhang, Hongjie; Garcia, Jose M","year":2015,"journal":"Expert opinion on pharmacotherapy, 16(8), 1245-53","doi":"10.1517/14656566.2015.1041500","pmid":"25945893","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Anamorelin administration in patients with non-small cell lung cancer (NSCLC) and cancer anorexia-cachexia syndrome (CACS) leads to increased appetite, body weight, and lean body mass, likely through ghrelin receptor agonism and growth hormone stimulation, with a favorable safety profile observed in clinical studies.","whyItMatters":"CACS significantly worsens outcomes in cancer patients by causing muscle wasting and weight loss. Anamorelin offers a novel approach by targeting multiple pathways involved in appetite and metabolism, potentially improving quality of life and survival.","specificNumbers":"","methodology":"This article is a review summarizing preclinical and clinical studies on anamorelin's pharmacodynamics, pharmacokinetics, efficacy, safety, and tolerability in treating CACS in NSCLC patients.","limitations":"The review does not specify the strength of evidence or detailed clinical trial data, and long-term safety and efficacy remain unestablished. Effects in cancer types other than NSCLC are also unknown."},{"rthcId":"RPEP-02849","title":"Design, synthesis, and characterization of BRC4 mutants based on the crystal structure of BRC4-RAD51(191-220).","authors":"Zhao, Dongxin; Lu, Kui","year":2015,"journal":"Journal of molecular modeling, 21(11), 299","doi":"10.1007/s00894-015-2831-x","pmid":"26522863","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Using the crystal structure of the BRC4-RAD51(191-220) complex, a series of BRC4 mutant peptides was designed with PyMOL and synthesized via Fmoc solid-phase methods to >95% purity. Circular dichroism spectroscopy revealed slight secondary structure changes in the mutant peptides, indicating that mutations at non-conserved sites in BRC4 can affect the interaction interface with RAD51. These structural changes provide insights into the binding rules governing BRCA2-RAD51 interaction.","whyItMatters":"BRCA2 mutations cause some of the most common hereditary cancers. Understanding exactly how BRCA2 controls RAD51-mediated DNA repair at the peptide level could lead to therapeutic peptides that either restore or modulate this interaction in cancer cells, opening new treatment approaches for BRCA2-mutant cancers.","specificNumbers":"","methodology":"Crystal structure-based peptide design using PyMOL software, followed by solid-phase peptide synthesis (Fmoc method), purification by reversed-phase HPLC (>95% purity), and structural characterization by circular dichroism spectroscopy.","limitations":"This study focused only on structural characterization without functional assays measuring actual RAD51 binding affinity or DNA repair activity. The circular dichroism changes were described as \"slight,\" making it difficult to assess functional significance. No cell-based or in vivo experiments were performed. The study is from 2015 and represents early-stage work in this peptide design approach."},{"rthcId":"RPEP-02850","title":"A Murine Hypertrophic Cardiomyopathy Model: The DBA/2J Strain.","authors":"Zhao, Wenyuan; Zhao, Tieqiang; Chen, Yuanjian; Zhao, Fengbo; Gu, Qingqing; Williams, Robert W; Bhattacharya, Syamal K; Lu, Lu; Sun, Yao","year":2015,"journal":"PloS one, 10(8), e0133132","doi":"10.1371/journal.pone.0133132","pmid":"26241864","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The DBA/2J mouse strain carries sequence variants in Mybpc3 and Myh7 genes and exhibits hallmark features of human hypertrophic cardiomyopathy, including increased heart weight, cardiomyocyte hypertrophy, elevated hypertrophy markers (β-MHC, ANP, BNP, α1-actin), and cardiac fibrosis with upregulated type I collagen and α-SMA, all occurring without hypertension or heart failure.","whyItMatters":"Identifying a natural mouse model that mirrors human HCM allows researchers to study genetic modifiers and disease mechanisms in a controlled setting, potentially accelerating discovery of treatments.","specificNumbers":"","methodology":"The study compared four-month-old male DBA/2J mice to C57BL/6J controls, assessing heart morphology, gene expression markers of hypertrophy and fibrosis, and cardiac function to characterize HCM features in the DBA/2J strain.","limitations":"The study focuses on male mice at a single age point and does not establish causality between specific gene variants and observed phenotypes; functional studies are needed to confirm mechanisms."},{"rthcId":"RPEP-02851","title":"Synthesis and biological evaluation of novel structure-related hGHRH agonistic analogs.","authors":"Zhou, Dong; You, Juan; Li, Qiu-Ying; Li, Hong-Zhi; Wu, Wen-Feng; Zhang, Xu-Dong; Zhang, Juan-Hui; Tang, Song-Shan; Wang, Yun-Ke; Liu, Tao","year":2015,"journal":"Growth factors (Chur, Switzerland), 33(2), 160-8","doi":"10.3109/08977194.2015.1010644","pmid":"25798996","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among the synthesized GHRH dimers, the 2F analog exhibited the highest potency (114 ± 16.6%) in stimulating rat growth hormone release and demonstrated the strongest receptor affinity in pituitary cell binding assays. The presence of an N-terminal single cyclic amino acid, specifically (1)Pro, was critical for enhanced stimulation compared to (1)Tyr-containing dimers.","whyItMatters":"Improving the potency and receptor affinity of GHRH analogs can lead to better therapeutic agents for growth hormone deficiencies. Understanding structure-activity relationships in GHRH dimers aids peptide drug design and optimization.","specificNumbers":"","methodology":"GHRH monomers were chemically synthesized and dimerized via incubation in NH4OH solution. The resulting dimers were evaluated through in vitro assays measuring rat growth hormone (rGH) release, receptor binding in pituitary homogenates, and fluorescent staining to assess cellular binding and distribution.","limitations":"The study did not specify the in vivo efficacy or safety of the dimers, and the sample size and detailed experimental conditions were not provided, limiting the assessment of translational potential."},{"rthcId":"RPEP-02852","title":"The effects of substance p on tendinopathy are dose-dependent: an in vitro and in vivo model study.","authors":"Zhou, Y; Zhou, B; Tang, K","year":2015,"journal":"The journal of nutrition, health & aging, 19(5), 555-61","doi":"10.1007/s12603-014-0576-3","pmid":"25923486","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Both low (0.1 nM) and high (1.0 nM) concentrations of Substance P enhanced tendon-derived stem cell (TDSC) proliferation in vitro. However, low-dose SP induced tenocyte-related gene expression (promoting healthy tendon cell identity), while high-dose SP induced non-tenocyte genes including PPARγ (a fat cell marker) and collagen type II (a cartilage marker).\n\nIn vivo, injecting low-dose SP (0.5 nmol) into rat patella tendons enhanced tenogenesis compared to both saline controls and high-dose SP. High-dose SP (5.0 nmol) induced tendinosis-like changes in the tendon. These findings demonstrate a clear dose-dependent switch from therapeutic to pathological effects.","whyItMatters":"Tendinopathy is extremely common and difficult to treat, affecting athletes and workers alike. Substance P levels are elevated in painful tendons, but it was unclear whether SP is part of the problem or part of the healing response. This study resolves that paradox: SP is both, depending on concentration. This has direct implications for developing peptide-based tendon therapies and understanding why some tendon injuries become chronic.","specificNumbers":"","methodology":"In vitro: tendon-derived stem cells were cultured with SP at 0.1 nM and 1.0 nM concentrations; proliferation capacity and gene expression (tenocyte vs. non-tenocyte markers) were measured. In vivo: SP was injected into rat patella tendons at 0.5 nmol and 5.0 nmol doses; histological changes were assessed compared to saline-injected controls.","limitations":"The study used rat models and isolated stem cells, which may not fully replicate human tendon biology. The specific SP concentrations that trigger the switch in humans are unknown. Only two dose levels were tested in each model, so the precise threshold between beneficial and harmful effects was not defined. Long-term outcomes of SP injection were not assessed."},{"rthcId":"RPEP-02853","title":"Intraperitoneal injection of the pancreatic peptide amylin potently reduces behavioral impairment and brain amyloid pathology in murine models of Alzheimer's disease.","authors":"Zhu, H; Wang, X; Wallack, M; Li, H; Carreras, I; Dedeoglu, A; Hur, J-Y; Zheng, H; Li, H; Fine, R; Mwamburi, M; Sun, X; Kowall, N; Stern, R A; Qiu, W Q","year":2015,"journal":"Molecular psychiatry, 20(2), 252-62","doi":"10.1038/mp.2014.17","pmid":"24614496","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Chronic intraperitoneal injections of amylin or pramlintide in Alzheimer's disease mouse models significantly reduced brain amyloid-beta burden and improved cognitive performance in behavioral tests. Both peptides increased amyloid-beta levels in cerebrospinal fluid and induced a surge of amyloid-beta in serum proportional to brain levels.","whyItMatters":"This research suggests amylin peptides can reduce harmful amyloid buildup in the brain and improve memory, offering a promising new approach for Alzheimer's treatment and diagnosis.","specificNumbers":"","methodology":"The study used murine models of Alzheimer's disease treated with chronic intraperitoneal injections of amylin or pramlintide. Behavioral tests (Y maze and Morris water maze) assessed cognitive function, while biochemical assays measured amyloid-beta concentrations in brain, cerebrospinal fluid, and serum. Additional intracerebroventricular injections and human plasma analyses were conducted to explore peptide effects and associations.","limitations":"The study was conducted in mouse models, so results may not fully translate to humans. The exact mechanisms by which amylin influences amyloid-beta transport and clearance require further investigation."},{"rthcId":"RPEP-02854","title":"Substance P and the neurokinin-1 receptor regulate electroencephalogram non-rapid eye movement sleep slow-wave activity locally.","authors":"Zielinski, M R; Karpova, S A; Yang, X; Gerashchenko, D","year":2015,"journal":"Neuroscience, 284, 260-272","doi":"10.1016/j.neuroscience.2014.08.062","pmid":"25301750","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Local cortical administration of a neurokinin-1 receptor (NK-1R) agonist, substance P-fragment 1,7, significantly enhanced slow-wave activity (SWA) in the ipsilateral hemisphere, while NK-1R antagonist injections attenuated SWA. These effects were hemisphere-specific and did not alter total non-rapid eye movement (NREM) or rapid eye movement (REM) sleep durations.","whyItMatters":"Understanding how substance P regulates slow-wave activity locally could help develop targeted therapies to improve sleep quality and address sleep disorders involving disrupted deep sleep.","specificNumbers":"","methodology":"The study involved local cortical injections of NK-1R agonist and antagonist in mice, with EEG recordings to measure slow-wave activity and sleep stages. Comparisons were made between ipsilateral and contralateral hemispheres relative to the EEG electrode and saline vehicle controls.","limitations":"The study was conducted in mice, which may limit direct applicability to humans, and the exact pathways linking substance P to sleep regulation require further exploration."},{"rthcId":"RPEP-02855","title":"The many faces of oxytocin: implications for psychiatry.","authors":"Zik, Jodi B; Roberts, David L","year":2015,"journal":"Psychiatry research, 226(1), 31-7","doi":"10.1016/j.psychres.2014.11.048","pmid":"25619431","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Oxytocin has multifaceted effects on social cognition, showing potential to improve social deficits in psychiatric disorders while possibly exacerbating social biases. Moderating factors influence whether oxytocin's effects are positive or negative, suggesting tailored approaches are necessary for therapeutic use.","whyItMatters":"Understanding oxytocin's dual effects is crucial for developing targeted psychiatric treatments that enhance social functioning without unintended negative consequences.","specificNumbers":"","methodology":"This study is a literature review examining recent findings on oxytocin's effects on social cognition and behavior, focusing on its implications for psychiatric disorders and the role of moderating factors.","limitations":"The review does not present new experimental data and the evidence strength and study types are not specified, limiting definitive conclusions."},{"rthcId":"RPEP-02856","title":"Khavinson 2016 Short Peptides Regulate Gene","authors":"","year":2016,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02857","title":"Travis 2016 Igf1 Prostate Meta","authors":"","year":2016,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02858","title":"VPAC1 receptor (Vipr1)-deficient mice exhibit ameliorated experimental autoimmune encephalomyelitis, with specific deficits in the effector stage.","authors":"Abad, Catalina; Jayaram, Bhavaani; Becquet, Laurine; Wang, Yuqi; O'Dorisio, M Sue; Waschek, James A; Tan, Yossan-Var","year":2016,"journal":"Journal of neuroinflammation, 13(1), 169","doi":"10.1186/s12974-016-0626-3","pmid":"27357191","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"VPAC1 knockout mice exhibited significantly reduced experimental autoimmune encephalomyelitis (EAE) severity, associated with decreased CNS chemokine expression and immune cell infiltration. The immunization phase was unaffected, but the effector phase of disease was impaired, indicating VPAC1's critical role in mediating immune cell invasion into the CNS.","whyItMatters":"Understanding VPAC1's role in autoimmune neuroinflammation could guide development of targeted therapies for diseases like multiple sclerosis by modulating immune cell entry into the brain and spinal cord.","specificNumbers":"","methodology":"EAE was induced in VPAC1-deficient and wild-type mice using MOG35-55 peptide. Disease progression was monitored over 30 days with clinical scoring, histology, PCR, and immunofluorescence. Immune function was assessed via antigen recall assays, adoptive transfer, and bone marrow chimera experiments. VPAC1 antagonists were administered to test receptor involvement.","limitations":"The study was conducted in mice, which may not fully replicate human disease. The exact molecular mechanisms by which VPAC1 influences immune cell trafficking remain to be elucidated."},{"rthcId":"RPEP-02859","title":"Non-coding Double-stranded RNA and Antimicrobial Peptide LL-37 Induce Growth Factor Expression from Keratinocytes and Endothelial Cells.","authors":"Adase, Christopher A; Borkowski, Andrew W; Zhang, Ling-Juan; Williams, Michael R; Sato, Emi; Sanford, James A; Gallo, Richard L","year":2016,"journal":"The Journal of biological chemistry, 291(22), 11635-46","doi":"10.1074/jbc.M116.725317","pmid":"27048655","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Double-stranded RNA acting as a damage signal significantly increased expression of multiple growth factors in keratinocytes, endothelial cells, and fibroblasts. When LL-37 was added alongside dsRNA — mimicking real wound conditions — RNA sequencing revealed even greater growth factor upregulation.\n\nSpecifically, keratinocytes exposed to both LL-37 and dsRNA showed increased expression of FGF2 (basic fibroblast growth factor), HBEGF (heparin-binding EGF-like growth factor), VEGFC (vascular endothelial growth factor C), betacellulin, EGF, epiregulin, and members of the TGF-β superfamily. These results were validated by quantitative PCR and ELISA, confirming that antimicrobial peptides play a direct role in stimulating tissue repair — not just fighting infection.","whyItMatters":"This study reveals that LL-37 does more than kill bacteria — it actively promotes wound healing by amplifying growth factor production. Understanding this dual role could lead to new wound-healing therapies that harness the body's own antimicrobial peptides to accelerate skin repair, particularly for chronic wounds that fail to heal normally.","specificNumbers":"","methodology":"Researchers exposed cultured human keratinocytes, endothelial cells, and fibroblasts to double-stranded RNA alone or combined with LL-37 peptide. They used RNA sequencing to map the full transcriptome response, then confirmed key findings with quantitative PCR and ELISA protein assays. The combined treatment was designed to mimic the molecular environment of a real skin wound.","limitations":"This was an in vitro study using cultured cells, so the results may not fully translate to living tissue. The study did not test specific dose-response relationships for LL-37 or measure how long the growth factor boost lasted. No animal or human wound models were used to confirm these effects in a real healing environment."},{"rthcId":"RPEP-02860","title":"Efficacy and Safety of Liraglutide Added to Capped Insulin Treatment in Subjects With Type 1 Diabetes: The ADJUNCT TWO Randomized Trial.","authors":"Ahrén, Bo; Hirsch, Irl B; Pieber, Thomas R; Mathieu, Chantal; Gómez-Peralta, Fernando; Hansen, Troels Krarup; Philotheou, Areti; Birch, Sune; Christiansen, Erik; Jensen, Thomas Jon; Buse, John B","year":2016,"journal":"Diabetes care, 39(10), 1693-701","doi":"10.2337/dc16-0690","pmid":"27493132","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02861","title":"Proglucagon-Derived Peptides Do Not Significantly Affect Acute Exocrine Pancreas in Rats.","authors":"Akalestou, Elina; Christakis, Ioannis; Solomou, Antonia M; Minnion, James S; Rutter, Guy A; Bloom, Stephen R","year":2016,"journal":"Pancreas, 45(7), 967-73","doi":"10.1097/MPA.0000000000000585","pmid":"26731187","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"None of the four proglucagon-derived peptides caused acute harm to the exocrine pancreas:\n\n- Plasma amylase did not increase after infusion of GLP-1, oxyntomodulin, glucagon, or exendin-4 (compared to vehicle and cholecystokinin controls)\n- None of the peptides caused significant cell proliferation in pancreatic acinar or ductal cells\n- None increased amylase secretion from isolated pancreatic cells\n- Oxyntomodulin specifically inhibited plasma amylase when co-administered with cholecystokinin, suggesting an active protective mechanism\n\nThis positions oxyntomodulin as potentially the safest proglucagon-derived peptide for obesity treatment regarding pancreatic risk.","whyItMatters":"Pancreatitis has been a persistent safety concern for GLP-1 receptor agonists, with some clinical reports suggesting an increased risk. This study provides reassuring preclinical evidence that these peptides don't acutely damage the pancreas. The finding that oxyntomodulin — a dual GLP-1/glucagon receptor agonist being developed for obesity — may actually protect against pancreatic stress is particularly encouraging for the development of dual-agonist therapies.","specificNumbers":"","methodology":"GLP-1, oxyntomodulin, glucagon, and exendin-4 were infused intravenously into anesthetized Wistar rats, and plasma amylase concentrations were measured as a marker of exocrine pancreatic stress. In vitro experiments tested each peptide's effect on amylase release and cell proliferation in rat pancreatic acinar cells (AR42J cell line) and primary isolated ductal cells.","limitations":"This study only assessed acute effects — long-term or chronic exposure effects could differ significantly. The study was conducted in rats, and rodent pancreatic physiology does not perfectly replicate human pancreatic responses. Only short-term amylase changes and cell proliferation were measured; other markers of pancreatic inflammation or injury were not assessed. The in vitro cell line (AR42J) may not fully represent normal pancreatic acinar cell behavior."},{"rthcId":"RPEP-02862","title":"Do blood plasma levels of oxytocin moderate the effect of nasally administered oxytocin on social orienting in high-functioning male adults with autism spectrum disorder?","authors":"Althaus, Monika; Groen, Yvonne; A Wijers, Albertus; Noltes, Henriette; Tucha, Oliver; Sweep, Fred C; Calcagnoli, Federica; Hoekstra, Pieter J","year":2016,"journal":"Psychopharmacology, 233(14), 2737-51","doi":"10.1007/s00213-016-4339-1","pmid":"27256356","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Baseline plasma oxytocin concentrations were higher in males with autism spectrum disorder (ASD) compared to controls. Higher baseline oxytocin levels in ASD participants were associated with larger treatment effects on social orienting after nasal oxytocin administration, while higher post-treatment plasma oxytocin in controls correlated with smaller treatment effects.","whyItMatters":"Understanding how baseline oxytocin levels affect treatment response can help tailor oxytocin-based therapies for social difficulties in autism, potentially improving their effectiveness.","specificNumbers":"","methodology":"A double-blind, placebo-controlled crossover trial was conducted with 31 males with ASD and 30 healthy males. Participants received nasal oxytocin or placebo and viewed images varying in emotional content while cardiac and cortical brain responses were measured.","limitations":"The study had a relatively small sample size and did not clarify the precise mechanisms of oxytocin absorption and central availability. The evidence strength and study type were not specified."},{"rthcId":"RPEP-02863","title":"Synergistic Increase of Serum BDNF in Alzheimer Patients Treated with Cerebrolysin and Donepezil: Association with Cognitive Improvement in ApoE4 Cases.","authors":"Alvarez, X Anton; Alvarez, Irene; Iglesias, Olalla; Crespo, Ignacio; Figueroa, Jesus; Aleixandre, Manuel; Linares, Carlos; Granizo, Elias; Garcia-Fantini, Manuel; Marey, Jose; Masliah, Eliezer; Winter, Stefan; Muresanu, Dafin; Moessler, Herbert","year":2016,"journal":"The international journal of neuropsychopharmacology, 19(6)","doi":"10.1093/ijnp/pyw024","pmid":"27207906","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02864","title":"Adaptive coding of the value of social cues with oxytocin, an fMRI study in autism spectrum disorder.","authors":"Andari, Elissar; Richard, Nathalie; Leboyer, Marion; Sirigu, Angela","year":2016,"journal":"Cortex; a journal devoted to the study of the nervous system and behavior, 76, 79-88","doi":"10.1016/j.cortex.2015.12.010","pmid":"26872344","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Intranasal oxytocin (24 IU) selectively enhanced activity in early visual areas when viewing faces versus non-social stimuli, and modulated amygdala and hippocampus activity depending on social context. Oxytocin increased mid-orbitofrontal cortex activity in response to fair partners and insula activity to unfair partners, correlating with improved behavioral trust allocation in individuals with ASD.","whyItMatters":"Understanding how oxytocin influences brain regions involved in social processing can guide development of treatments to improve social functioning in autism. This study highlights oxytocin's role in adapting brain responses to social value cues.","specificNumbers":"","methodology":"The study administered a single dose of 24 IU intranasal oxytocin to 20 individuals with autism spectrum disorder. Functional MRI was used during an interactive ball game and a face-matching task to measure brain activity changes in response to social cues.","limitations":"The study had a small sample size and lacked a control group without ASD. The single-dose design limits understanding of long-term effects. The evidence strength and study type were not specified."},{"rthcId":"RPEP-02865","title":"LCZ696 (Valsartan/Sacubitril)--A Possible New Treatment for Hypertension and Heart Failure.","authors":"Andersen, Mathilde Borring; Simonsen, Ulf; Wehland, Markus; Pietsch, Jessica; Grimm, Daniela","year":2016,"journal":"Basic & clinical pharmacology & toxicology, 118(1), 14-22","doi":"10.1111/bcpt.12453","pmid":"26280447","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"LCZ696, a combination of valsartan and sacubitril, demonstrated greater reductions in blood pressure and decreased mortality and morbidity in patients with heart failure with reduced ejection fraction compared to current treatments. It also lowered blood pressure and NT-pro-BNP levels in patients with heart failure with preserved ejection fraction.","whyItMatters":"LCZ696 offers a novel dual-action approach that may improve treatment effectiveness for hypertension and heart failure, conditions with significant health impacts worldwide. Enhancing peptide preservation while blocking harmful pathways could lead to better patient outcomes.","specificNumbers":"","methodology":"This MiniReview summarizes data from four clinical trials (NCT01193101, NCT00549770, NCT00887588, NCT01035255) assessing LCZ696's effects on hypertension and heart failure patients. The review compares outcomes with those from existing ACE inhibitors and angiotensin receptor blockers.","limitations":"The review is based on early trial data with limited long-term follow-up, and the overall study type and evidence strength are not clearly defined. More extensive and longer-duration studies are needed."},{"rthcId":"RPEP-02866","title":"Anti-inflammatory and immunomodulatory effects of Aquaphilus dolomiae extract on in vitro models.","authors":"Aries, Marie-Françoise; Hernandez-Pigeon, Hélène; Vaissière, Clémence; Delga, Hélène; Caruana, Antony; Lévêque, Marguerite; Bourrain, Muriel; Ravard Helffer, Katia; Chol, Bertrand; Nguyen, Thien; Bessou-Touya, Sandrine; Castex-Rizzi, Nathalie","year":2016,"journal":"Clinical, cosmetic and investigational dermatology, 9, 421-434","doi":null,"pmid":"27877060","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The Aquaphilus dolomiae extract (ES0) inhibited multiple inflammatory mediators and cytokines involved in atopic dermatitis in keratinocytes and immune cells. It also activated innate immune receptors (TLR2, TLR4, TLR5) and induced antimicrobial peptides, indicating a broad immunomodulatory effect.","whyItMatters":"This research identifies a natural extract with multiple anti-inflammatory and immune-regulating effects, which could lead to new treatments for atopic dermatitis, a condition with limited effective therapies.","specificNumbers":"","methodology":"In vitro cell models relevant to atopic dermatitis were used, including human keratinocytes and CD4+ lymphocytes. The effects of the ES0 extract on inflammatory mediators, cytokine production, receptor activation, and antimicrobial peptide expression were measured using various biochemical assays.","limitations":"The study was conducted entirely in vitro, so effects in living organisms or humans remain to be confirmed. The exact clinical efficacy and safety of the extract require further investigation."},{"rthcId":"RPEP-02867","title":"Incretin based drugs and the risk of pancreatic cancer: international multicentre cohort study.","authors":"Azoulay, Laurent; Filion, Kristian B; Platt, Robert W; Dahl, Matthew; Dormuth, Colin R; Clemens, Kristin K; Durand, Madeleine; Juurlink, David N; Targownik, Laura E; Turin, Tanvir C; Paterson, J Michael; Ernst, Pierre","year":2016,"journal":"BMJ (Clinical research ed.), 352, i581","doi":"10.1136/bmj.i581","pmid":"26888382","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The use of incretin-based drugs was not associated with an increased risk of pancreatic cancer compared with sulfonylureas, with a pooled adjusted hazard ratio of 1.02 (95% CI 0.84 to 1.23). No variation in risk was observed by drug class or duration of use.","whyItMatters":"This study provides important safety data reassuring that incretin-based drugs, widely used for type 2 diabetes, do not increase pancreatic cancer risk, addressing previous concerns about their long-term safety.","specificNumbers":"","methodology":"A population-based cohort study combining health records from six sites in Canada, the US, and the UK, including 972,384 patients initiating antidiabetic drugs from 2007 to 2013. Nested case-control analyses matched pancreatic cancer cases with controls, and hazard ratios were estimated with a one-year lag for drug exposure.","limitations":"The median follow-up was relatively short (1.3 to 2.8 years), which may limit detection of long-term cancer risks due to latency. Residual confounding cannot be fully excluded."},{"rthcId":"RPEP-02868","title":"Physicochemical characterization of native glycyl-l-histidyl-l-lysine tripeptide for wound healing and anti-aging: a preformulation study for dermal delivery.","authors":"Badenhorst, Travis; Svirskis, Darren; Wu, Zimei","year":2016,"journal":"Pharmaceutical development and technology, 21(2), 152-60","doi":"10.3109/10837450.2014.979944","pmid":"25384620","tags":["ghk-cu"],"studyType":"laboratory","evidenceStrength":"preliminary","keyFinding":"GHK-Cu (glycyl-histidyl-lysine copper) is surprisingly stable in water and at pH 4.5–7.4 buffers, remaining intact for at least two weeks even at 60°C. However, it breaks down under basic (alkaline) and oxidative conditions through hydrolytic cleavage, with histidine identified as one of three degradation products.\n\nThe peptide is highly water-loving (hydrophilic), with log D values between -2.38 and -2.49, which explains why it struggles to penetrate skin on its own. It was compatible with Span 60-based niosomes (a type of delivery vesicle) but degraded in the presence of negatively charged lipids like dicetyl phosphate. These findings provide a practical roadmap for formulating GHK-Cu into effective topical products.","whyItMatters":"GHK-Cu is one of the most popular peptides in anti-aging skincare, but its extreme hydrophilicity means it can’t easily cross the skin barrier. This preformulation study identifies exactly what conditions keep GHK-Cu stable and which delivery vehicles are compatible, providing the scientific foundation for creating topical products that actually work rather than just sitting on the skin surface.","specificNumbers":"log D: -2.38 to -2.49 · Stable at pH 4.5–7.4 · Stable for 2+ weeks at 60°C · 3 degradation products identified · First-order degradation kinetics","methodology":"Researchers used validated reversed-phase HPLC to measure GHK-Cu concentrations and mass spectrometry to identify degradation products. They tested the peptide’s stability under acidic, basic, oxidative, and thermal stress conditions. Solubility and distribution coefficients were measured across a range of pH values. Compatibility was assessed with potential formulation ingredients including niosome components.","limitations":"This is a pure chemistry/formulation study with no biological testing — it tells us how to keep GHK-Cu stable in a product but not whether the formulated product actually improves skin or wound healing. No skin penetration studies were conducted. The niosome compatibility testing was limited to a few lipid types."},{"rthcId":"RPEP-02869","title":"Substance P promotes the recovery of oxidative stress-damaged retinal pigmented epithelial cells by modulating Akt/GSK-3β signaling.","authors":"Baek, Sang-Min; Yu, Seung-Young; Son, Youngsook; Hong, Hyun Sook","year":2016,"journal":"Molecular vision, 22, 1015-23","doi":null,"pmid":"27582624","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Substance P treatment activates the Akt/GSK-3β signaling pathway via the neurokinin 1 receptor, promoting cell survival, proliferation, and reducing apoptosis in retinal pigmented epithelial cells damaged by oxidative stress.","whyItMatters":"Understanding how substance P protects retinal cells from oxidative damage could lead to new treatments for eye diseases like age-related macular degeneration that currently lack effective therapies.","specificNumbers":"","methodology":"Retinal pigmented epithelial cells were exposed to hydrogen peroxide to induce oxidative stress. The effects of substance P on cell viability, proliferation, apoptosis, and signaling pathway activation were assessed in vitro using various biochemical assays.","limitations":"The study was conducted in vitro, so results may not fully translate to living organisms. The exact clinical relevance and long-term effects of substance P treatment remain to be established."},{"rthcId":"RPEP-02870","title":"Stable gastric pentadecapeptide BPC 157 heals rectovaginal fistula in rats.","authors":"Baric, Marko; Sever, Anita Zenko; Vuletic, Lovorka Batelja; Rasic, Zarko; Sever, Marko; Drmic, Domagoj; Pavelic-Turudic, Tatjana; Sucic, Mario; Vrcic, Hrvoje; Seiwerth, Sven; Sikiric, Predrag","year":2016,"journal":"Life sciences, 148, 63-70","doi":"10.1016/j.lfs.2016.02.029","pmid":"26872976","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BPC 157 administered either orally or intraperitoneally at microgram and nanogram doses significantly improved healing of rectovaginal fistulas in rats. Both rectal and vaginal defects were ameliorated, fistula leakage ceased, and complications such as adhesions and intestinal obstruction were reduced, with microscopic and macroscopic evidence of tissue repair.","whyItMatters":"This study highlights BPC 157's potential as a non-surgical therapy to promote healing of complex fistulas, a condition that currently lacks effective medical treatments. It may open new avenues for peptide-based therapies in tissue repair.","specificNumbers":"","methodology":"Rats with surgically induced rectovaginal fistulas received BPC 157 either orally in drinking water or via intraperitoneal injection at two dose levels. Healing was assessed at multiple time points up to 21 days by evaluating fistula defects, leakage, adhesion formation, and intestinal obstruction, compared to saline or water controls.","limitations":"The study was conducted in rats, so results may not directly translate to humans. The exact mechanisms of BPC 157’s healing effects were not fully elucidated, and the study design details and evidence strength were not specified."},{"rthcId":"RPEP-02871","title":"Regulation of energy balance by a gut-brain axis and involvement of the gut microbiota.","authors":"Bauer, Paige V; Hamr, Sophie C; Duca, Frank A","year":2016,"journal":"Cellular and molecular life sciences : CMLS, 73(4), 737-55","doi":"10.1007/s00018-015-2083-z","pmid":"26542800","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review describes a comprehensive model of gut-brain energy regulation:\n\n- Enteroendocrine cells sense ingested nutrients and release gut peptides (CCK, GLP-1, PYY)\n- These peptides signal via two pathways: paracrine signaling through vagal and non-vagal neuronal relays, and endocrine signaling via the bloodstream\n- Central nervous system integrates these signals to generate responses that reduce food intake and increase energy expenditure\n- Gut microbiota modulate this gut-brain axis, potentially influencing the development of obesity\n- Disruptions in this signaling system may contribute to impaired energy homeostasis and weight gain","whyItMatters":"The gut peptides reviewed here — especially GLP-1 — are now the basis of the most successful obesity drugs in history (semaglutide, tirzepatide). This review provides the foundational science explaining why these drugs work: they mimic or enhance natural gut-brain signaling that controls appetite. Understanding the microbiome's role adds another potential therapeutic target.","specificNumbers":"","methodology":"This is a comprehensive review article examining current hypotheses and recent research on nutrient sensing mechanisms of enteroendocrine cells, gut peptide signaling pathways, gut-to-brain communication, and the influence of gut microbiota on energy balance regulation.","limitations":"As a 2016 review, it predates much of the clinical success of GLP-1 receptor agonists for obesity. The mechanisms of microbiota influence on the gut-brain axis were largely hypothetical at the time. The review does not cover dual or triple agonist approaches (GLP-1/GIP, GLP-1/GIP/glucagon) that have since emerged."},{"rthcId":"RPEP-02872","title":"Investigation of bombesin peptide as a targeting ligand for the gastrin releasing peptide (GRP) receptor.","authors":"Begum, Anjuman Ara; Moyle, Peter M; Toth, Istvan","year":2016,"journal":"Bioorganic & medicinal chemistry, 24(22), 5834-5841","doi":"10.1016/j.bmc.2016.09.039","pmid":"27670095","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02873","title":"The influence of rough lipopolysaccharide structure on molecular interactions with mammalian antimicrobial peptides.","authors":"Bello, Gianluca; Bodin, Alice; Lawrence, M Jayne; Barlow, David; Mason, A James; Barker, Robert D; Harvey, Richard D","year":2016,"journal":"Biochimica et biophysica acta, 1858(2), 197-209","doi":"10.1016/j.bbamem.2015.11.007","pmid":"26592318","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The study found that shorter Rc lipopolysaccharide structures promote more ordered lipid packing than longer Ra structures, which affects the membrane penetration of antimicrobial peptides. LL37 showed deeper penetration and greater membrane perturbation compared to LFb, which localized more at the membrane interface.","whyItMatters":"Understanding how bacterial surface structures influence antimicrobial peptide activity can help design better peptide-based therapies against infections and improve knowledge of host defense mechanisms.","specificNumbers":"","methodology":"The researchers used solid state deuterium NMR, Brewster angle microscopy, neutron reflectivity, and subphase injection techniques to study peptide interactions with lipid bilayers and monolayers containing different E. coli lipopolysaccharide chemotypes.","limitations":"The study used model membrane systems rather than live bacteria, which may not fully replicate biological complexity. The exact in vivo relevance of the findings remains to be confirmed."},{"rthcId":"RPEP-02874","title":"Vasoactive intestinal peptide, whose receptor-mediated signalling may be defective in alopecia areata, provides protection from hair follicle immune privilege collapse.","authors":"Bertolini, M; Pretzlaff, M; Sulk, M; Bähr, M; Gherardini, J; Uchida, Y; Reibelt, M; Kinori, M; Rossi, A; Bíró, T; Paus, R","year":2016,"journal":"The British journal of dermatology, 175(3), 531-41","doi":"10.1111/bjd.14645","pmid":"27059672","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"This study provided the first evidence that VIP receptors (VPAC1 and VPAC2) are expressed in the epithelium of healthy human hair follicles at both gene and protein levels. In lesional hair bulbs of alopecia areata patients, VIP receptor protein expression was significantly downregulated, while VIP-positive nerve fibers remained present — suggesting a defect in receptor-mediated signaling rather than peptide supply.\n\nIn hair follicle organ culture, VIP treatment protected follicles from interferon-γ-induced immune privilege collapse but did not fully restore immune privilege once it had already collapsed. This indicates VIP acts as a preventive 'guardian' of hair follicle immune privilege rather than a restorative agent.","whyItMatters":"Alopecia areata affects millions of people worldwide and current treatments are limited. This study identifies a specific molecular defect — reduced VIP receptor signaling — in the disease process and demonstrates that the peptide VIP can guard against the immune attack that causes hair loss. This opens a new therapeutic avenue: delivering VIP or VIP receptor agonists to the scalp could potentially prevent disease progression.","specificNumbers":"","methodology":"VIP and VIP receptor expression were assessed in human scalp hair follicles from healthy volunteers and lesional skin from alopecia areata patients using gene expression analysis and immunohistochemistry. Hair follicle organ cultures were treated with VIP and/or interferon-γ to model immune privilege collapse and test VIP's protective effects. Key immune privilege markers were quantified by immunohistomorphometry.","limitations":"This was a pilot study using in vitro organ culture models, not a clinical trial. The sample sizes for both healthy and alopecia areata tissue were limited. VIP could protect but not fully restore immune privilege, which may limit its therapeutic window. The route and formulation for delivering VIP therapeutically to hair follicles were not addressed."},{"rthcId":"RPEP-02875","title":"The role of kisspeptin and RFRP in the circadian control of female reproduction.","authors":"Beymer, Matthew; Henningsen, Jo; Bahougne, Thibault; Simonneaux, Valérie","year":2016,"journal":"Molecular and cellular endocrinology, 438, 89-99","doi":"10.1016/j.mce.2016.06.026","pmid":"27364888","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Kisspeptin (Kp) and RFRP neurons are positioned at a critical interface between the suprachiasmatic nucleus (SCN) — the brain's master circadian clock — and GnRH neurons, which control the hormonal cascade leading to ovulation. Kisspeptin stimulates GnRH release, while RFRP generally inhibits it, creating a push-pull system for precisely timing the preovulatory hormone surge.\n\nThe review also reports that these neuropeptide neurons are themselves part of the multi-oscillatory circadian system, meaning they don't just relay clock signals but actively participate in circadian timekeeping for reproduction. Recent investigations suggest potential therapeutic applications of these peptides in human reproductive disorders.","whyItMatters":"Understanding the precise timing mechanisms behind ovulation has direct implications for fertility treatment. Many reproductive disorders — including some forms of infertility, polycystic ovary syndrome, and hypothalamic amenorrhea — may involve disrupted peptide signaling between the circadian clock and the reproductive axis. Kisspeptin is already being investigated as a therapeutic agent for triggering ovulation in fertility clinics, and deeper understanding of its circadian role could improve treatment timing and outcomes.","specificNumbers":"","methodology":"This is a narrative review article synthesizing findings from the previous decade of research on kisspeptin and RFRP neuropeptides. It integrates evidence from animal studies (rodent models primarily), neuroanatomical tracing, electrophysiology, and emerging human clinical data to build a comprehensive model of circadian control of female reproduction.","limitations":"As a review article, this paper synthesizes existing research rather than presenting new experimental data. Much of the evidence comes from rodent models, and the translation to human reproductive physiology is not fully established. The therapeutic potential of kisspeptin and RFRP in humans was discussed as preliminary and speculative at the time of publication. The exact mechanisms by which the SCN clock communicates with kisspeptin and RFRP neurons were not fully resolved."},{"rthcId":"RPEP-02876","title":"Anti-Müllerian hormone and polycystic ovary syndrome.","authors":"Bhide, Priya; Homburg, Roy","year":2016,"journal":"Best practice & research. Clinical obstetrics & gynaecology, 37, 38-45","doi":"10.1016/j.bpobgyn.2016.03.004","pmid":"27103234","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02877","title":"Differential expression of antimicrobial peptides in psoriasis and psoriatic arthritis as a novel contributory mechanism for skin and joint disease heterogeneity.","authors":"Bierkarre, H; Harder, J; Cuthbert, R; Emery, P; Leuschner, I; Mrowietz, U; Hedderich, J; McGonagle, D; Gläser, R","year":2016,"journal":"Scandinavian journal of rheumatology, 45(3), 188-96","doi":"10.3109/03009742.2015.1091497","pmid":"26599663","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Psoriatic skin showed broad, strong expression of all eight antimicrobial peptides tested, with particularly robust keratinocyte expression. In contrast, psoriatic arthritis synovial tissue only expressed S100 A8, S100 A9, and HNP1-3, and only in the synovium sublining layer — not in the lining layer.\n\nCritically, hBD-2, hBD-3, psoriasin (S100 A7), RNase 7, and cathelicidin LL-37 were completely undetectable in the joint tissue of PsA, RA, or OA patients. Since hBD-2 is genetically linked to psoriasis susceptibility, its skin-only expression provides a molecular explanation for why psoriasis and psoriatic arthritis behave as distinct — though related — diseases.","whyItMatters":"This research provides a molecular explanation for one of dermatology's and rheumatology's key puzzles: why only about 30% of psoriasis patients develop psoriatic arthritis. By showing that skin-specific antimicrobial peptides like hBD-2 — which is genetically linked to psoriasis — are not expressed in joints at all, the study demonstrates that the innate immune environment differs fundamentally between these two tissues. This could eventually inform diagnostic tools that predict joint disease risk and guide tissue-specific treatment strategies.","specificNumbers":"","methodology":"The study examined knee biopsies from 22 patients (10 with psoriatic arthritis, 8 with rheumatoid arthritis, and 4 with osteoarthritis), plus lesional and non-lesional skin biopsies from 4 psoriasis patients and 4 healthy controls. Immunohistochemistry was performed using antibodies against eight AMPs: S100 A8, S100 A9, HNP1-3, hBD-2, hBD-3, cathelicidin LL-37, psoriasin, and RNase 7. Expression was scored semi-quantitatively across tissue compartments.","limitations":"The sample sizes are small (22 joint biopsies, 8 skin biopsies), which limits statistical power. Semi-quantitative immunohistochemistry scoring is subjective and less precise than quantitative methods like ELISA or mass spectrometry. The study only examined knee joints, so findings may not generalize to other affected joints. Skin biopsies were from different patients than joint biopsies, preventing direct within-patient comparison."},{"rthcId":"RPEP-02878","title":"Substance P and its Inhibition in Ocular Inflammation.","authors":"Bignami, Fabio; Rama, Paolo; Ferrari, Giulio","year":2016,"journal":"Current drug targets, 17(11), 1265-74","doi":null,"pmid":"26477461","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Substance P (SP) mediates neurogenic inflammation in the eye through binding to the neurokinin-1 receptor (NK-1R), which is expressed on nerves, immune cells, and epithelial cells. SP's inflammatory effects include:\n\n- Increased microvascular permeability and vasodilatation\n- Plasma extravasation and tissue edema\n- Stimulation of macrophages to release interleukins, chemokines, and growth factors\n\nInhibition of SP activity — through blocking neuropeptide release or using NK-1R antagonists — ameliorates ocular inflammation, restores immune privilege, and improves clinical endpoints including corneal opacity, ocular perforation, and angiogenesis. These effects have been demonstrated in animal models and in human eye diseases.","whyItMatters":"Inflammatory eye diseases can cause severe vision loss, and current treatments often rely on broad immunosuppression with significant side effects. Targeting Substance P specifically could provide a more precise anti-inflammatory approach with fewer systemic effects. Understanding this neuropeptide's role also reveals how the nervous system directly contributes to eye inflammation.","specificNumbers":"","methodology":"This is a literature review summarizing published research on Substance P's role in ocular inflammation, with emphasis on the ocular surface. The review covers the molecular mechanisms of SP-mediated inflammation, evidence from animal models, and therapeutic applications of SP blockade in human eye diseases.","limitations":"As a review article, no new experimental data is presented. The evidence varies in quality across the animal models and human studies reviewed. The exact clinical efficacy, optimal dosing, and safety profile of SP inhibitors specifically for ocular use in humans require further investigation through clinical trials."},{"rthcId":"RPEP-02879","title":"Endogenous opiates and behavior: 2014.","authors":"Bodnar, Richard J","year":2016,"journal":"Peptides, 75, 18-70","doi":"10.1016/j.peptides.2015.10.009","pmid":"26551874","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The 2014 research collectively demonstrates that endogenous opioid peptides and their receptors are involved in a wide range of behavioral and physiological processes including pain modulation, stress response, addiction mechanisms, learning and memory, and various autonomic functions.","whyItMatters":"Understanding how endogenous opioids regulate behavior and physiology is crucial for developing better treatments for pain, addiction, mood disorders, and other health conditions involving the opioid system.","specificNumbers":"","methodology":"This is an annual review compiling and summarizing findings from multiple molecular, pharmacological, and genetic studies published in 2014 that examined endogenous opioid peptides, receptors, agonists, and antagonists and their behavioral effects.","limitations":"As a review, it summarizes existing studies without new experimental data; the evidence strength and study types vary across the included research, limiting uniform conclusions."},{"rthcId":"RPEP-02880","title":"Role of capsaicin-sensitive nerves and tachykinins in mast cell tryptase-induced inflammation of murine knees.","authors":"Borbély, Éva; Sándor, Katalin; Markovics, Adrienn; Kemény, Ágnes; Pintér, Erika; Szolcsányi, János; Quinn, John P; McDougall, Jason J; Helyes, Zsuzsanna","year":2016,"journal":"Inflammation research : official journal of the European Histamine Research Society ... [et al.], 65(9), 725-36","doi":"10.1007/s00011-016-0954-x","pmid":"27251170","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Mast cell tryptase induces synovial vasodilatation, edema, mechanical hyperalgesia, and spontaneous pain in mouse knees. Capsaicin-sensitive afferents and TRPV1 receptors are essential for vasodilatation, while tachykinins and their NK1 receptor mediate edema and pain responses.","whyItMatters":"Understanding the neural and molecular pathways of inflammation and pain in arthritis can help develop targeted therapies that reduce joint swelling and pain without broadly suppressing the immune system.","specificNumbers":"","methodology":"The study used gene-deleted mice lacking TRPV1, substance P/neurokinin A, or NK1 receptors, compared to wildtype controls. Mast cell tryptase was administered intraarticularly or topically. Inflammation and pain were assessed by measuring knee diameter, blood flow, mechanical sensitivity, and weight distribution over 6 hours, alongside immunoassays for cytokines and neuropeptides.","limitations":"The study was conducted in mice, which may not fully replicate human arthritis. The acute 6-hour observation period limits understanding of longer-term effects. The exact study type and evidence strength were not specified."},{"rthcId":"RPEP-02881","title":"Amylin structure-function relationships and receptor pharmacology: implications for amylin mimetic drug development.","authors":"Bower, Rebekah L; Hay, Debbie L","year":2016,"journal":"British journal of pharmacology, 173(12), 1883-98","doi":"10.1111/bph.13496","pmid":"27061187","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review highlights the complex structure-function relationships of amylin and its receptors, emphasizing the challenges posed by amylin's aggregation and solubility issues. Insights from related peptides like CGRP are used to inform the design of more potent and stable amylin mimetics, including peptide hybrids.","whyItMatters":"Understanding amylin's structure and receptor interactions is crucial for developing better amylin-based drugs that can more effectively manage diabetes and metabolic disorders.","specificNumbers":"","methodology":"This is a literature review analyzing existing research on amylin's structure, receptor pharmacology, and related peptides to inform drug development strategies.","limitations":"As a review, it does not present new experimental data and the evidence strength and study type are not specified, limiting direct conclusions about efficacy."},{"rthcId":"RPEP-02882","title":"Peptide-based synthetic pulmonary surfactant for the treatment of respiratory distress disorders.","authors":"Braide-Moncoeur, Otonye; Tran, Nhi T; Long, Joanna R","year":2016,"journal":"Current opinion in chemical biology, 32, 22-8","doi":"10.1016/j.cbpa.2016.02.012","pmid":"26970670","tags":["therapeutic-peptides","respiratory"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"KL4 (sinapultide) is the first synthetic peptide designed to replace surfactant protein B in lung surfactant therapies. Its formulation, Surfaxin, demonstrated that synthetic peptide-based surfactants can replace animal-derived surfactants for treating respiratory distress syndromes and acute lung injury. Structural studies revealed KL4 has adaptive helical properties — its shape changes depending on lipid environment and pH — with a five-amino-acid repeat pattern that enables it to interact differently with various lipid layers.\n\nThis structural plasticity appears to be key to how KL4 helps form stable DPPC monolayers at the air-water interface in the lungs — the same function that natural surfactant protein B performs to keep lung air sacs from collapsing.","whyItMatters":"Premature babies and patients with acute lung injury need surfactant therapy to keep their lungs from collapsing. Current treatments use surfactant extracted from cow or pig lungs, which raises supply, safety, and consistency concerns. A fully synthetic peptide-based alternative could eliminate animal sourcing, standardize production, and potentially expand access to a life-saving therapy — especially important for neonatal intensive care units worldwide.","specificNumbers":"KL4 = penta-residue repeat peptide · first FDA-approved peptide-based surfactant · replaces surfactant protein B","methodology":"Review of published research on KL4 (sinapultide) structure, function, and clinical application as a synthetic lung surfactant, including molecular characterization studies using biophysical methods to understand peptide-lipid interactions.","limitations":"This is a review focused on one peptide (KL4) and its structural mechanism. Clinical comparison data between synthetic and animal-derived surfactants across different patient populations is limited. The molecular characterization is detailed but translating structural insights to improved clinical formulations remains an ongoing challenge."},{"rthcId":"RPEP-02883","title":"Evidence of substance P autocrine circuitry that involves TNF-α, IL-6, and PGE2 in endogenous pyrogen-induced fever.","authors":"Brito, Haissa Oliveira; Barbosa, Felipe L; Reis, Renata Cristiane Dos; Fraga, Daniel; Borges, Beatriz S; Franco, Celia R C; Zampronio, Aleksander Roberto","year":2016,"journal":"Journal of neuroimmunology, 293, 1-7","doi":"10.1016/j.jneuroim.2016.01.016","pmid":"27049554","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Substance P mediates fever by inducing a prostaglandin-dependent response and is released following stimulation by TNF-α, IL-6, PGE2, CRF, endogenous opioids, and ET-1. Blocking the neurokinin-1 receptor with SR140333B reduces fever induced by these endogenous pyrogens.","whyItMatters":"Understanding how substance P interacts with inflammatory molecules to cause fever can help develop targeted treatments for fever and inflammation-related conditions.","specificNumbers":"","methodology":"The study used intracerebroventricular injections of substance P, neurokinin-1 receptor antagonist SR140333B, and various inflammatory mediators in rats to observe effects on fever and receptor expression in the hypothalamus.","limitations":"The exact study type and evidence strength were not specified, and the findings are based on animal models which may not fully translate to humans."},{"rthcId":"RPEP-02884","title":"Neutrophil-derived alpha defensins control inflammation by inhibiting macrophage mRNA translation.","authors":"Brook, Matthew; Tomlinson, Gareth H; Miles, Katherine; Smith, Richard W P; Rossi, Adriano G; Hiemstra, Pieter S; van 't Wout, Emily F A; Dean, Jonathan L E; Gray, Nicola K; Lu, Wuyuan; Gray, Mohini","year":2016,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 113(16), 4350-5","doi":"10.1073/pnas.1601831113","pmid":"27044108","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02885","title":"Antimicrobial Activity of Lactoferrin-Related Peptides and Applications in Human and Veterinary Medicine.","authors":"Bruni, Natascia; Capucchio, Maria Teresa; Biasibetti, Elena; Pessione, Enrica; Cirrincione, Simona; Giraudo, Leonardo; Corona, Antonio; Dosio, Franco","year":2016,"journal":"Molecules (Basel, Switzerland), 21(6)","doi":"10.3390/molecules21060752","pmid":"27294909","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Lactoferrin-derived peptides, especially lactoferricin, exhibit stronger antimicrobial activity than the intact lactoferrin protein. These peptides have demonstrated broad-spectrum antibacterial, antifungal, and antiparasitic effects with potential applications in treating human and veterinary infections.","whyItMatters":"Identifying effective antimicrobial peptides from natural sources like lactoferrin could lead to new treatments for infections, addressing antibiotic resistance and improving health outcomes in humans and animals.","specificNumbers":"","methodology":"This study reviews existing research on antimicrobial peptides derived from lactoferrin, focusing on their biological activities and potential medical applications. It synthesizes findings from various experimental studies without conducting new experiments.","limitations":"The study is a review and does not provide new experimental data; the strength of evidence and clinical efficacy require further validation through controlled trials."},{"rthcId":"RPEP-02886","title":"Long-term Outcome after Robotic-assisted Gastroplication in Adolescents: Hunger Hormone and Food Preference Changes Two Case Reports.","authors":"Calcaterra, Valeria; Cena, Hellas; Fonte, Maria Luisa; De Amici, Mara; Vandoni, Matteo; Albanesi, Michela; Pelizzo, Gloria","year":2016,"journal":"Journal of clinical research in pediatric endocrinology, 8(2), 250-6","doi":"10.4274/jcrpe.2283","pmid":"26757831","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Robotic-assisted gastroplication in two adolescent patients resulted in sustained weight loss, decreased waist circumference, altered resting energy expenditure, and favorable changes in hunger hormones ghrelin and leptin. These hormonal changes were associated with improved food preferences and eating behaviors.","whyItMatters":"Understanding how weight loss surgery affects hunger hormones and food preferences in adolescents helps improve long-term obesity treatments and supports the development of multidisciplinary care strategies.","specificNumbers":"","methodology":"This study followed two obese adolescent females who underwent robotic-assisted gastroplication. Researchers monitored anthropometric data, metabolic and hormonal profiles, and eating behaviors over two to three years post-surgery.","limitations":"The study is limited by its very small sample size of only two patients and lacks a control group, making it difficult to generalize findings or establish causality."},{"rthcId":"RPEP-02887","title":"Simulated GI digestion of dietary protein: Release of new bioactive peptides involved in gut hormone secretion.","authors":"Caron, Juliette; Cudennec, Benoit; Domenger, Dorothée; Belguesmia, Yanath; Flahaut, Christophe; Kouach, Mostafa; Lesage, Jean; Goossens, Jean-François; Dhulster, Pascal; Ravallec, Rozenn","year":2016,"journal":"Food research international (Ottawa, Ont.), 89(Pt 1), 382-390","doi":"10.1016/j.foodres.2016.08.033","pmid":"28460928","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Three novel peptides (ANVST, TKAVEH, KAAVT) were identified that stimulate GLP-1 secretion, while the peptide VAAA inhibits DPP-IV, an enzyme that modulates GLP-1 activity. Additionally, two peptide groups rich in aromatic amino acids were strongly involved in stimulating CCK release.","whyItMatters":"Understanding which peptides from protein digestion influence gut hormones can help develop functional foods or supplements that promote satiety and aid weight management through natural appetite regulation.","specificNumbers":"","methodology":"The study used in vitro simulated gastrointestinal digestion of dietary proteins followed by purification and sequencing of peptide fractions using LC-MS-MS. The effects of these peptides on gut hormone secretion and DPP-IV enzyme activity were tested in STC-1 cell models.","limitations":"The study was conducted in vitro using cell models, so the effects of these peptides in humans after actual digestion and absorption remain to be confirmed."},{"rthcId":"RPEP-02888","title":"VIP impairs acquisition of the macrophage proinflammatory polarization profile.","authors":"Carrión, Mar; Pérez-García, Selene; Martínez, Carmen; Juarranz, Yasmina; Estrada-Capetillo, Lizbeth; Puig-Kröger, Amaya; Gomariz, Rosa P; Gutiérrez-Cañas, Irene","year":2016,"journal":"Journal of leukocyte biology, 100(6), 1385-1393","doi":null,"pmid":"27381006","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"VIP exposure in vitro shifts GM-CSF-polarized proinflammatory macrophages (GM-MØ) toward an anti-inflammatory phenotype by upregulating M-CSF macrophage markers and reducing proinflammatory cytokine expression. VIP receptors VPAC1 and VPAC2 are more highly expressed in proinflammatory macrophages and RA synovial macrophages, indicating VIP’s potential to modulate macrophage polarization in inflammatory conditions.","whyItMatters":"Understanding how VIP modulates macrophage polarization offers insight into new therapeutic strategies for autoimmune diseases like rheumatoid arthritis, where controlling inflammation is crucial.","specificNumbers":"","methodology":"The study used in vitro polarization of human macrophages with GM-CSF to induce a proinflammatory profile and M-CSF for an anti-inflammatory profile. Researchers measured expression of VIP receptors and gene markers, then treated GM-MØ with VIP to assess changes in macrophage phenotype and cytokine profiles.","limitations":"The study was conducted in vitro, so results may not fully translate to in vivo conditions. The exact mechanisms of VIP’s modulation of macrophage function require further exploration."},{"rthcId":"RPEP-02889","title":"Leukocyte opioid receptors mediate analgesia via Ca(2+)-regulated release of opioid peptides.","authors":"Celik, Melih Ö; Labuz, Dominika; Henning, Karen; Busch-Dienstfertig, Melanie; Gaveriaux-Ruff, Claire; Kieffer, Brigitte L; Zimmer, Andreas; Machelska, Halina","year":2016,"journal":"Brain, behavior, and immunity, 57, 227-242","doi":"10.1016/j.bbi.2016.04.018","pmid":"27139929","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Opioid receptors on immune cells (leukocytes) can trigger the release of three opioid peptides — Met-enkephalin, β-endorphin, and dynorphin A (1-17) — which then act on nearby nerve cell receptors to relieve neuropathic pain. This challenges the classical view that opioid pain relief works only through receptors on neurons.\n\nThe researchers mapped the complete signaling pathway: activation of leukocyte opioid receptors triggers a Gαi/o-Gβγ protein cascade through phospholipase C and IP3 receptors, releasing intracellular calcium, which drives opioid peptide secretion. When leukocytes were depleted, pain relief from exogenous opioids was significantly reduced and could only be restored by transplanting wild-type immune cells — not those lacking opioid receptors.","whyItMatters":"This research reveals that immune cells are active participants in pain control, not just bystanders. By showing that opioid receptors on leukocytes drive the release of the body's own painkilling peptides, this work opens a fundamentally new approach to pain management — one that could potentially harness the immune system's natural analgesic capacity rather than relying solely on drugs that act on nerve cells.","specificNumbers":"3 opioid peptides released (Met-enkephalin, β-endorphin, dynorphin A) · δ-, μ-, and κ-opioid receptor subtypes involved · Gαi/o-Gβγ-PLC-IP3-Ca²⁺ signaling pathway","methodology":"Researchers used a mouse model of neuropathic pain created by chronic constriction injury of the sciatic nerve. They injected opioid receptor agonists at the damaged nerve site and measured pain relief using von Frey filaments (which test sensitivity to touch). They systematically blocked or removed components of the signaling pathway — depleting leukocytes, using genetic knockouts, and applying pharmacological inhibitors — to identify the mechanism. They also tested opioid peptide release from immune cells ex vivo.","limitations":"This was a mouse study, so findings need to be confirmed in humans. The chronic constriction injury model, while well-established, may not fully replicate all forms of human neuropathic pain. The relative contributions of different leukocyte subtypes to opioid peptide release were not fully characterized."},{"rthcId":"RPEP-02890","title":"Growth Hormone Releasing Peptide-2 Attenuation of Protein Kinase C-Induced Inflammation in Human Ovarian Granulosa Cells.","authors":"Chao, Yi-Ning; Sun, David; Peng, Yen-Chun; Wu, Yuh-Lin","year":2016,"journal":"International journal of molecular sciences, 17(8)","doi":"10.3390/ijms17081359","pmid":"27548147","tags":[],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"GHRP-2 (a synthetic ghrelin analog) suppressed inflammation in human ovarian granulosa cells through multiple mechanisms. It reduced the expression and secretion of two key inflammatory mediators — COX-2 and IL-8 — by blocking the p38, JNK, and NF-κB signaling pathways that drive their production.\n\nBeyond blocking production, GHRP-2 also accelerated the breakdown of already-existing COX-2 and IL-8 proteins by activating both proteasomal and lysosomal degradation pathways. The anti-inflammatory effect depended on two phosphatases (MKP-1 and PP2A), suggesting GHRP-2 works by activating the cell's own inflammation-shutoff switches.","whyItMatters":"GHRP-2 is primarily known as a growth hormone-releasing peptide, but this study reveals a completely separate function: powerful anti-inflammatory activity in reproductive cells. COX-2 and IL-8 drive inflammation during ovulation and in conditions like endometriosis and ovarian hyperstimulation syndrome. The finding that a ghrelin-receptor peptide can suppress ovarian inflammation through multiple mechanisms suggests growth hormone secretagogues may have therapeutic applications far beyond growth hormone release.","specificNumbers":"COX-2 and IL-8 protein and mRNA reduced · PGE2 and IL-8 secretion reduced · p38 and JNK phosphorylation inhibited · NF-κB nuclear translocation blocked · AP-1 reporter activation reduced · MKP-1 and PP2A involvement confirmed","methodology":"In vitro study using human ovarian granulosa KGN cells. Inflammation was induced with a protein kinase C activator (PDD). GHRP-2 was applied to assess anti-inflammatory effects. Researchers measured protein expression, mRNA levels, promoter activity, protein secretion, signaling pathway activation (Western blot, reporter assays), protein degradation pathways, and the role of specific phosphatases using inhibitors.","limitations":"Single cell line (KGN) — results may not apply to primary granulosa cells or the complex ovarian environment in vivo. Chemically induced inflammation (PDD) may not fully reflect physiological inflammatory processes during ovulation. No animal or human data. The dose of GHRP-2 used may not correspond to pharmacologically achievable concentrations in the ovary."},{"rthcId":"RPEP-02891","title":"Enhanced responsiveness of Ghsr Q343X rats to ghrelin results in enhanced adiposity without increased appetite.","authors":"Chebani, Yacine; Marion, Candice; Zizzari, Philippe; Chettab, Khadidja; Pastor, Marie; Korostelev, Marie; Geny, David; Epelbaum, Jacques; Tolle, Virginie; Morisset-Lopez, Séverine; Pantel, Jacques","year":2016,"journal":"Science signaling, 9(424), ra39","doi":"10.1126/scisignal.aae0374","pmid":"27095593","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Rats carrying the Ghsr(Q343X) mutation exhibited enhanced G protein-dependent signaling in response to ghrelin, leading to increased adiposity and body weight without increased food intake. These rats also showed improved body weight stability during caloric restriction and impaired glucose tolerance under normal conditions.","whyItMatters":"Understanding how specific receptor mutations affect ghrelin signaling can help identify new targets for obesity and metabolic disorder treatments by modulating fat accumulation independently of appetite.","specificNumbers":"","methodology":"The study used genetically modified rats with the Ghsr(Q343X) mutation affecting receptor signaling. Researchers assessed receptor signaling in cells and measured physiological responses in rats, including body weight, fat accumulation, glucose tolerance, and response to ghrelin or GHSR agonists.","limitations":"The study does not specify long-term metabolic outcomes or effects in humans, and the exact mechanisms linking receptor signaling changes to glucose intolerance require further investigation."},{"rthcId":"RPEP-02892","title":"Clinical Application of Radiolabeled RGD Peptides for PET Imaging of Integrin αvβ3.","authors":"Chen, Haojun; Niu, Gang; Wu, Hua; Chen, Xiaoyuan","year":2016,"journal":"Theranostics, 6(1), 78-92","doi":"10.7150/thno.13242","pmid":"26722375","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02893","title":"Protective effect of gelatin peptides from pacific cod skin against photoaging by inhibiting the expression of MMPs via MAPK signaling pathway.","authors":"Chen, Tiejun; Hou, Hu; Fan, Yan; Wang, Shikai; Chen, Qianru; Si, Leilei; Li, Bafang","year":2016,"journal":"Journal of photochemistry and photobiology. B, Biology, 165, 34-41","doi":"10.1016/j.jphotobiol.2016.10.015","pmid":"27768951","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Gelatin hydrolysate (CH) from Pacific cod skin significantly inhibited the UV-induced upregulation and activity of MMP-1, MMP-3, and MMP-9 in mouse skin, preserved collagen content, and suppressed MAPK pathway activation including ERK and p38 phosphorylation, thereby protecting against photoaging.","whyItMatters":"Understanding how natural peptides inhibit enzymes that degrade collagen can lead to new treatments or skincare products that prevent or reduce skin aging caused by UV exposure. This could improve skin health and appearance.","specificNumbers":"","methodology":"The study used a mouse skin photoaging model exposed to UV irradiation. Quantitative real-time PCR and ELISA assays measured MMP expression and activity, while molecular analyses assessed MAPK signaling pathway components after treatment with gelatin hydrolysate (CH) derived from Pacific cod skin.","limitations":"The study was conducted in a mouse model, so results may not fully translate to humans. The exact dosage and delivery method for optimal effects in humans remain to be established."},{"rthcId":"RPEP-02894","title":"High expression of substance P and its receptor neurokinin-1 receptor in colorectal cancer is associated with tumor progression and prognosis.","authors":"Chen, Xiao-Yi; Ru, Guo-Qing; Ma, Ying-Yu; Xie, Jun; Chen, Wan-Yuan; Wang, Hui-Ju; Wang, Shi-Bing; Li, Li; Jin, Ke-Tao; He, Xiang-Lei; Mou, Xiao-Zhou","year":2016,"journal":"OncoTargets and therapy, 9, 3595-602","doi":"10.2147/OTT.S102356","pmid":"27366097","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Both SP and NK1R were significantly upregulated in CRC tissue compared to adjacent normal tissue (P<0.001). High SP expression was significantly associated with lymph node metastasis (P<0.001). High NK1R expression was significantly related to TNM stage (P=0.010) and lymph node metastasis (P=0.019).\n\nSP and NK1R expression were highly correlated with each other (r=0.419, P<0.001), suggesting coordinated upregulation of the signaling pathway in tumors.\n\nSurvival analysis showed significantly poorer prognosis for patients with high SP or NK1R expression (P<0.05). Multivariate Cox regression confirmed that SP expression was independently correlated with survival, alongside lymph node metastasis and distant metastasis — meaning SP levels predict outcomes even after accounting for other known prognostic factors.","whyItMatters":"Colorectal cancer is one of the most common cancers worldwide, and predicting which tumors will spread aggressively is crucial for treatment decisions. Finding that Substance P independently predicts survival adds a potentially useful biomarker to the clinician's toolkit. More importantly, NK-1R antagonists already exist as approved drugs (for nausea), raising the possibility of repurposing them for cancer treatment.","specificNumbers":"","methodology":"Immunohistochemistry was performed on tissue microarrays containing 267 matched pairs of colorectal cancer and adjacent normal tissue. SP and NK1R expression levels were scored and correlated with clinicopathological features including TNM stage, lymph node metastasis, and distant metastasis. Survival analysis used Kaplan-Meier curves with log-rank tests, and multivariate analysis used Cox proportional hazards regression.","limitations":"This is an observational study that demonstrates correlation, not causation — it cannot prove that SP/NK1R directly drives cancer progression. No functional experiments were performed to test whether blocking SP/NK1R signaling would alter tumor behavior. The study population is from a single institution, which may limit generalizability. Immunohistochemistry scoring can be subjective, and the study does not report inter-observer reliability."},{"rthcId":"RPEP-02895","title":"Identification of bioactive peptide from Oreochromis niloticus skin gelatin.","authors":"Choonpicharn, Sadabpong; Tateing, Suriya; Jaturasitha, Sanchai; Rakariyatham, Nuansri; Suree, Nuttee; Niamsup, Hataichanoke","year":2016,"journal":"Journal of food science and technology, 53(2), 1222-9","doi":"10.1007/s13197-015-2091-x","pmid":"27162402","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Two peptides were identified from trypsin-digested Nile tilapia skin gelatin: GPEGPAGAR (810.87 Da) and GETGPAGPAGAAGPAGPR (1490.61 Da). The trypsin B fraction showed ACE inhibitory activity of 59.32 ± 9.97% and radical scavenging activity of 8.16 ± 2.18 µg trolox/mg peptide. The trypsin A fraction had the greatest reducing power at 5.138 ± 1.060 µM trolox/mg peptide.\n\nMolecular docking analysis suggested the shorter peptide may fit slightly better into the ACE binding cleft, but both synthetic peptides showed no significant difference in ACE inhibitory activity in vitro, confirming their dual potential as antioxidant and antihypertensive agents.","whyItMatters":"High blood pressure affects over a billion people worldwide, and many patients seek natural alternatives to pharmaceutical ACE inhibitors. This study demonstrates that bioactive peptides with genuine ACE inhibitory activity can be extracted from fish processing waste — turning an environmental burden into a potentially valuable health product while supporting sustainability in the aquaculture industry.","specificNumbers":"","methodology":"Nile tilapia skin gelatin was digested with trypsin and the hydrolysate was purified by gel filtration chromatography. Fractions were tested for reducing power, radical scavenging activity, and ACE inhibition. The most active fraction was analyzed by MALDI-TOF/TOF mass spectrometry and identified using Mascot sequence matching. Peptide sequences were confirmed through molecular docking simulations against ACE and validated with in vitro ACE inhibition assays using synthetic versions of the identified peptides.","limitations":"This is entirely an in vitro study with no animal or human testing of blood pressure effects. The ACE inhibition percentage (59.32%) was measured in a test tube and may not translate to meaningful blood pressure reduction when consumed orally, as the peptides may be further degraded during digestion. No bioavailability or pharmacokinetic data was provided. The study did not compare these peptides to existing ACE inhibitor drugs. Single-source material from one fish species limits generalizability."},{"rthcId":"RPEP-02896","title":"Antagonists of growth hormone-releasing hormone receptor induce apoptosis specifically in retinoblastoma cells.","authors":"Chu, Wai Kit; Law, Ka Sin; Chan, Sun On; Yam, Jason Cheuk Sing; Chen, Li Jia; Zhang, Hao; Cheung, Herman S; Block, Norman L; Schally, Andrew V; Pang, Chi Pui","year":2016,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 113(50), 14396-14401","doi":null,"pmid":"27911838","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The GHRH receptor (GHRH-R) was found to be highly expressed in retinoblastoma cells but not in other retinal cells, providing a selective target. Two GHRH-R antagonists, MIA-602 and MIA-690, induced specific apoptosis in retinoblastoma cells without triggering cell death in retinal pigmented epithelial cells.\n\nGene expression profiling revealed that GHRH-R antagonists downregulated cell proliferation genes while upregulating apoptotic genes in the cancer cells. The mechanism exploits the fact that retinoblastoma arises from cone precursor cells with high MDM2 levels that suppress p53-mediated apoptosis — the GHRH-R antagonists appear to restore these suppressed cell death pathways.","whyItMatters":"Retinoblastoma primarily affects young children, and current treatments (chemotherapy, cryotherapy, laser therapy, and sometimes eye removal) can have devastating consequences for a child's vision and quality of life. A targeted therapy that kills only cancer cells while preserving healthy retinal tissue could transform treatment outcomes, potentially saving both the eye and vision in children with this disease.","specificNumbers":"","methodology":"Researchers first characterized GHRH receptor expression across retinoblastoma cell lines and other retinal cell types. They then treated both cancer and normal retinal cells with two GHRH-R antagonists (MIA-602, MIA-690) and measured apoptosis. Gene expression profiling was performed to identify the molecular pathways regulated by the antagonists, revealing changes in proliferation and apoptosis-related gene networks.","limitations":"This is an in vitro (cell culture) study that has not been validated in animal models or human patients. The selectivity demonstrated between retinoblastoma cells and retinal pigmented epithelial cells may not fully represent the complexity of the eye in vivo, where other cell types and the tumor microenvironment could affect drug behavior. Dosing, delivery to the eye, and potential systemic effects of GHRH-R antagonism were not addressed."},{"rthcId":"RPEP-02897","title":"The spinal generator of ejaculation: Functional consequences of chronic spinalization and effect of substance P in anesthetized rats.","authors":"Chéhensse, C; Clément, P; Joussain, C; Bernabé, J; Giuliano, F","year":2016,"journal":"Neuroscience, 336, 12-19","doi":"10.1016/j.neuroscience.2016.08.044","pmid":"27592274","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Chronic spinal cord transection in rats does not impair the function of the spinal generator of ejaculation (SGE). Substance P administration into the SGE area induces ejaculation and lowers the stimulation threshold needed to trigger ejaculation, effects reversed by a neurokinin-1 receptor antagonist.","whyItMatters":"Understanding how substance P influences spinal ejaculation mechanisms could lead to new treatments for anejaculation in men with spinal cord injuries, improving their sexual health and quality of life.","specificNumbers":"","methodology":"The study used anesthetized rats with complete thoracic spinal cord transection (T9). Electrical stimulation was applied to the SGE, and ejaculation occurrence and peripheral responses were recorded. Substance P was locally administered to assess its effects on ejaculation and stimulation thresholds.","limitations":"The study was conducted in anesthetized rats, which may not fully replicate natural conditions or human physiology. The evidence strength and study type were not specified."},{"rthcId":"RPEP-02898","title":"Whole-grain pasta reduces appetite and meal-induced thermogenesis acutely: a pilot study.","authors":"Cioffi, Iolanda; Santarpia, Lidia; Vaccaro, Andrea; Iacone, Roberto; Labruna, Giuseppe; Marra, Maurizio; Contaldo, Franco; Kristensen, Mette; Pasanisi, Fabrizio","year":2016,"journal":"Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme, 41(3), 277-83","doi":"10.1139/apnm-2015-0446","pmid":"26863235","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Whole-grain pasta consumption acutely increased postprandial fullness and decreased hunger sensations compared to refined-grain pasta meals. It also resulted in significantly lower postprandial energy expenditure and meal-induced thermogenesis. However, no pasta meal variation improved postprandial glucose, insulin, or other metabolic markers.","whyItMatters":"Understanding how whole-grain foods affect appetite and energy use can help develop dietary strategies to manage weight and metabolic health. This study suggests whole-grain pasta may support appetite control without negatively impacting metabolism.","specificNumbers":"","methodology":"A randomized crossover design was used with 8 healthy participants consuming four isocaloric pasta meals on separate days. Appetite sensations, blood samples, and resting energy expenditure were measured before and up to 4 hours after meals. Repeated-measures ANCOVA analyzed differences between meal types.","limitations":"The small sample size of 8 participants limits generalizability. The study only assessed acute effects after a single meal, so long-term impacts remain unknown. The evidence strength and study type were not clearly defined."},{"rthcId":"RPEP-02899","title":"Bremelanotide for female sexual dysfunctions in premenopausal women: a randomized, placebo-controlled dose-finding trial.","authors":"Clayton, Anita H; Althof, Stanley E; Kingsberg, Sheryl; DeRogatis, Leonard R; Kroll, Robin; Goldstein, Irwin; Kaminetsky, Jed; Spana, Carl; Lucas, Johna; Jordan, Robert; Portman, David J","year":2016,"journal":"Women's health (London, England), 12(3), 325-37","doi":"10.2217/whe-2016-0018","pmid":"27181790","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Bremelanotide administered subcutaneously at doses of 1.25 and 1.75 mg significantly increased the number of satisfying sexual events per month and improved scores on female sexual function and distress scales compared to placebo in premenopausal women with sexual dysfunction.","whyItMatters":"This study provides evidence that bremelanotide is a promising treatment option for female sexual dysfunction, a condition with limited pharmacological therapies. It supports further development of melanocortin receptor agonists for sexual health.","specificNumbers":"","methodology":"A randomized, placebo-controlled, dose-finding trial was conducted with 327 premenopausal women who self-administered bremelanotide or placebo subcutaneously as desired over 12 weeks. Primary and secondary endpoints measured changes in sexual satisfaction and function.","limitations":"The study duration was relatively short at 12 weeks, and long-term safety and efficacy remain unknown. The evidence strength and study type were not clearly specified, limiting full assessment of the findings."},{"rthcId":"RPEP-02900","title":"Naturally occurring mitochondrial-derived peptides are age-dependent regulators of apoptosis, insulin sensitivity, and inflammatory markers.","authors":"Cobb, Laura J; Lee, Changhan; Xiao, Jialin; Yen, Kelvin; Wong, Richard G; Nakamura, Hiromi K; Mehta, Hemal H; Gao, Qinglei; Ashur, Carmel; Huffman, Derek M; Wan, Junxiang; Muzumdar, Radhika; Barzilai, Nir; Cohen, Pinchas","year":2016,"journal":"Aging, 8(4), 796-809","doi":"10.18632/aging.100943","pmid":"27070352","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02901","title":"In vivo high-resolution magic angle spinning magnetic and electron paramagnetic resonance spectroscopic analysis of mitochondria-targeted peptide in Drosophila melanogaster with trauma-induced thoracic injury.","authors":"Constantinou, Caterina; Apidianakis, Yiorgos; Psychogios, Nikolaos; Righi, Valeria; Mindrinos, Michael N; Khan, Nadeem; Swartz, Harold M; Szeto, Hazel H; Tompkins, Ronald G; Rahme, Laurence G; Tzika, A Aria","year":2016,"journal":"International journal of molecular medicine, 37(2), 299-308","doi":"10.3892/ijmm.2015.2426","pmid":"26648055","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Trauma in Drosophila melanogaster induces insulin resistance and mitochondrial uncoupling, as evidenced by altered NMR and EPR spectroscopic profiles. Treatment with the mitochondria-targeted peptide SS-31 normalized these metabolic dysfunctions, indicating its potential to attenuate trauma-associated pathological changes.","whyItMatters":"Understanding how trauma disrupts mitochondrial function and insulin signaling can guide development of targeted therapies. SS-31’s ability to restore mitochondrial health highlights its therapeutic potential for trauma-related conditions.","specificNumbers":"","methodology":"The study induced non-lethal thoracic trauma in fruit flies and analyzed gene expression changes related to mitochondrial and insulin signaling pathways. In vivo high-resolution NMR and EPR spectroscopy were used to assess mitochondrial function and redox status. The effects of the peptide SS-31 on these parameters were then evaluated.","limitations":"The study was conducted in fruit flies, which may limit direct applicability to humans. The exact study type and evidence strength were not specified, requiring cautious interpretation."},{"rthcId":"RPEP-02902","title":"Inflammation in acute CNS injury: a focus on the role of substance P.","authors":"Corrigan, F; Vink, R; Turner, R J","year":2016,"journal":"British journal of pharmacology, 173(4), 703-15","doi":"10.1111/bph.13155","pmid":"25827155","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Substance P expression increases after acute CNS injury, with the magnitude of release correlating to both the frequency and severity of the insult. SP release directly promotes blood-brain barrier permeability, vasogenic edema formation, neuronal injury, and worse functional outcomes.\n\nNK1 receptor antagonists that block Substance P's actions showed high therapeutic benefit in both focal and diffuse models of traumatic brain injury, as well as in ischemic stroke models. The therapeutic window extends up to 12 hours post-injury, making this a potentially practical intervention for emergency medicine settings.","whyItMatters":"There are no effective drug treatments for the secondary brain damage that occurs after traumatic brain injury or stroke. Identifying Substance P as a key driver of this damage, and showing that blocking it with existing drug classes works within a 12-hour window, points to a realistic new therapeutic strategy. NK1 receptor antagonists already exist (some are approved for other uses like anti-nausea), which could accelerate clinical development.","specificNumbers":"","methodology":"This is a narrative review synthesizing published preclinical research on neurogenic inflammation after acute CNS injury. The authors reviewed evidence from animal models of focal and diffuse traumatic brain injury and ischemic stroke, focusing on Substance P release patterns, blood-brain barrier changes, edema formation, and the effects of NK1 receptor antagonist treatment.","limitations":"This is a review article based primarily on preclinical animal model data. No human clinical trial data are presented. The 12-hour therapeutic window was demonstrated in animal models and may differ in humans. The translation from rodent brain injury models to human TBI and stroke is notoriously challenging. Long-term safety and efficacy of NK1 receptor antagonists in CNS injury patients are unknown."},{"rthcId":"RPEP-02903","title":"Neurogenic inflammation after traumatic brain injury and its potentiation of classical inflammation.","authors":"Corrigan, Frances; Mander, Kimberley A; Leonard, Anna V; Vink, Robert","year":2016,"journal":"Journal of neuroinflammation, 13(1), 264","doi":null,"pmid":"27724914","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"TRP channels (TRPV1 and TRPA1) are activated by mechanical forces during brain injury, causing the release of substance P. This neuropeptide then drives multiple inflammatory processes: activating microglia and astrocytes, degranulating mast cells, promoting immune cell migration into the brain, and critically, increasing blood-brain barrier permeability through caveolae-mediated transcellular transport. This neurogenic inflammation creates a positive feedback loop with classical inflammation — bradykinin and prostaglandins from classical pathways further stimulate TRP channels, perpetuating neuropeptide release and escalating damage.","whyItMatters":"Clinical trials targeting inflammation after traumatic brain injury have repeatedly failed. This review proposes a compelling explanation: treatments have only addressed classical inflammation while ignoring the neurogenic component driven by substance P and other neuropeptides. If the neurogenic pathway is indeed a key initiating event, targeting it — or targeting both pathways simultaneously — could lead to the first effective anti-inflammatory therapies for brain injury.","specificNumbers":"","methodology":"This is a narrative review that synthesizes existing evidence from molecular, cellular, and preclinical studies on neurogenic inflammation following traumatic brain injury. The authors integrate findings on TRP channel activation, substance P signaling, blood-brain barrier permeability changes, and glial cell activation to propose a unified model of neuroinflammatory amplification.","limitations":"This is a review paper synthesizing existing evidence, not presenting new experimental data. The proposed model of neurogenic-classical inflammatory feedback has not been directly validated in a single comprehensive study. Clinical evidence for targeting both pathways simultaneously in TBI patients does not yet exist. The relative contributions of neurogenic versus classical inflammation may vary by injury type and severity."},{"rthcId":"RPEP-02904","title":"Utility of the CKD273 peptide classifier in predicting chronic kidney disease progression.","authors":"Critselis, Elena; Lambers Heerspink, Hiddo","year":2016,"journal":"Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 31(2), 249-54","doi":"10.1093/ndt/gfv062","pmid":"25791724","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02905","title":"Agonistic analogs of growth hormone releasing hormone (GHRH) promote wound healing by stimulating the proliferation and survival of human dermal fibroblasts through ERK and AKT pathways.","authors":"Cui, Tengjiao; Jimenez, Joaquin J; Block, Norman L; Badiavas, Evangelos V; Rodriguez-Menocal, Luis; Vila Granda, Ailin; Cai, Renzhi; Sha, Wei; Zarandi, Marta; Perez, Roberto; Schally, Andrew V","year":2016,"journal":"Oncotarget, 7(33), 52661-52672","doi":"10.18632/oncotarget.11024","pmid":"27494841","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The GHRH analogs MR-409 and MR-502 significantly increased proliferation of human dermal fibroblasts by over 50% in vitro and improved cell survival under stress. MR-409 applied topically in vivo accelerated wound closure in a dose-dependent manner and reduced fibrosis, acting through MEK/ERK and PI3K/AKT pathways independent of IGF-1 receptor signaling.","whyItMatters":"Finding agents that promote fibroblast growth and survival can improve wound healing outcomes. These GHRH analogs resist degradation and activate key cell survival pathways, making them promising candidates for therapeutic development.","specificNumbers":"","methodology":"The study used in vitro experiments with primary human dermal fibroblasts to assess proliferation and survival after treatment with GHRH analogs MR-409 and MR-502. In vivo wound healing was evaluated by topical application of MR-409 on animal models, with histological analysis of wound contraction and fibrosis.","limitations":"The study does not specify the clinical trial phase or long-term safety data. The animal model results may not fully translate to humans without further testing."},{"rthcId":"RPEP-02906","title":"Amyloidogenesis of the amylin analogue pramlintide.","authors":"da Silva, Dayana Cabral; Fontes, Giselle N; Erthal, Luiza C S; Lima, Luís Maurício T R","year":2016,"journal":"Biophysical chemistry, 219, 1-8","doi":"10.1016/j.bpc.2016.09.007","pmid":"27665170","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Pramlintide, a triple proline amylinomimetic, was shown to assemble into multimers and form amyloid fibrils in vitro in a pH-dependent manner within hours, as demonstrated by ion mobility spectrometry, thioflavin T fluorescence, electron microscopy, atomic force microscopy, and X-ray diffraction.","whyItMatters":"Understanding pramlintide's ability to form amyloid fibers is crucial for peptide drug development and safety, as amyloid formation can impact drug stability and potential side effects in diabetic treatments.","specificNumbers":"","methodology":"The study used ion mobility spectrometry-based mass spectrometry to detect pramlintide multimers and monitored amyloid fibril formation in vitro using thioflavin T fluorescence assays, peptide solubility quantification, transmission electron microscopy, atomic force microscopy, and X-ray diffraction.","limitations":"The study was conducted in vitro and may not fully represent amyloid formation behavior in living organisms; the clinical implications of pramlintide amyloidogenesis remain unclear."},{"rthcId":"RPEP-02907","title":"GHRH excess and blockade in X-LAG syndrome.","authors":"Daly, Adrian F; Lysy, Philippe A; Desfilles, Céline; Rostomyan, Liliya; Mohamed, Amira; Caberg, Jean-Hubert; Raverot, Veronique; Castermans, Emilie; Marbaix, Etienne; Maiter, Dominique; Brunelle, Chloe; Trivellin, Giampaolo; Stratakis, Constantine A; Bours, Vincent; Raftopoulos, Christian; Beauloye, Veronique; Barlier, Anne; Beckers, Albert","year":2016,"journal":"Endocrine-related cancer, 23(3), 161-70","doi":"10.1530/ERC-15-0478","pmid":"26671997","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A young female patient with sporadic X-LAG syndrome showed consistently elevated circulating GHRH levels accompanied by marked GH and prolactin hypersecretion. In vitro, the GHRH receptor antagonist acetyl-(d-Arg2)-GHRH(1-29) amide blocked GHRH-induced GH stimulation and, importantly, also significantly reduced baseline GH release when used alone.\n\nPasireotide (a somatostatin analog) inhibited GH secretion, but octreotide did not. A ghrelin receptor agonist and inverse agonist produced modest but statistically significant changes in GH secretion. These data suggest hypothalamic GHRH dysregulation is part of X-LAG syndrome pathology and that GHRH blockade could be a therapeutic strategy.","whyItMatters":"X-LAG syndrome causes extreme childhood overgrowth that is challenging to manage surgically or medically. Identifying GHRH hypersecretion as a driver and showing that a peptide antagonist can block hormone release in vitro provides a new therapeutic target. This finding could lead to medical treatments that reduce the need for repeated pituitary surgeries in affected children.","specificNumbers":"","methodology":"Researchers performed serial hormonal profiles on a young female patient with sporadic X-LAG syndrome, including measurement of circulating GHRH, GH, and prolactin levels. After neurosurgical tumor resection, primary pituitary tumor cells were cultured and tested in vitro with GHRH, the GHRH receptor antagonist, pasireotide, octreotide, and ghrelin receptor modulators to assess their effects on hormone secretion.","limitations":"This is a single-patient case study with in vitro experiments, severely limiting generalizability to other X-LAG patients. The in vitro results may not directly translate to in vivo therapeutic efficacy. The GHRH receptor antagonist used is a research tool, not a clinically available drug. The mechanisms connecting GPR101 gene duplication to hypothalamic GHRH dysregulation are still speculative. Long-term effects of GHRH blockade in growing children are unknown."},{"rthcId":"RPEP-02908","title":"Human gut endogenous proteins as a potential source of angiotensin-I-converting enzyme (ACE-I)-, renin inhibitory and antioxidant peptides.","authors":"Dave, Lakshmi A; Hayes, Maria; Montoya, Carlos A; Rutherfurd, Shane M; Moughan, Paul J","year":2016,"journal":"Peptides, 76, 30-44","doi":"10.1016/j.peptides.2015.11.003","pmid":"26617077","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Human gut endogenous proteins (GEP) can be digested to release bioactive peptides with angiotensin-I-converting enzyme (ACE-I) inhibitory, renin inhibitory, and antioxidant activities. These peptides may contribute to immune regulation and normal physiological functions.","whyItMatters":"Identifying gut-derived bioactive peptides expands the understanding of natural mechanisms regulating blood pressure and oxidative stress, which could lead to novel therapeutic peptides or functional foods.","specificNumbers":"","methodology":"This is a review article that compiles and discusses existing data on endogenous gut proteins and their potential to generate bioactive peptides through gastrointestinal digestion.","limitations":"The article is a review and does not present new experimental data; the actual bioavailability and in vivo effects of gut-derived peptides require further investigation."},{"rthcId":"RPEP-02909","title":"Endothelin.","authors":"Davenport, Anthony P; Hyndman, Kelly A; Dhaun, Neeraj; Southan, Christopher; Kohan, Donald E; Pollock, Jennifer S; Pollock, David M; Webb, David J; Maguire, Janet J","year":2016,"journal":"Pharmacological reviews, 68(2), 357-418","doi":"10.1124/pr.115.011833","pmid":"26956245","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02910","title":"Regulation of α-Transducin and α-Gustducin Expression by a High Protein Diet in the Pig Gastrointestinal Tract.","authors":"De Giorgio, Roberto; Mazzoni, Maurizio; Vallorani, Claudia; Latorre, Rocco; Bombardi, Cristiano; Bacci, Maria Laura; Forni, Monica; Falconi, Mirella; Sternini, Catia; Clavenzani, Paolo","year":2016,"journal":"PloS one, 11(2), e0148954","doi":"10.1371/journal.pone.0148954","pmid":"26871573","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The study demonstrated a significant increase in α-transducin and α-gustducin immunoreactive cells in the pig gastrointestinal tract after short-term (3 days) and long-term (30 days) high protein diets. Notably, α-transducin-IR cells increased in the pyloric mucosa in both diet durations, while α-gustducin-IR cells increased significantly only after the long-term diet. These cells co-expressed hormones such as serotonin, ghrelin, cholecystokinin, and peptide YY, indicating a role in metabolic and satiety signaling.","whyItMatters":"Understanding how diet influences taste receptor signaling in the gut can provide insights into mechanisms controlling metabolism and appetite. This knowledge may help develop dietary strategies or peptide-based therapies to regulate satiety and metabolic health.","specificNumbers":"","methodology":"The study used immunohistochemical analysis to measure α-transducin and α-gustducin expressing cells in various regions of the pig gastrointestinal tract after feeding pigs either a control diet or a high protein diet for 3 or 30 days. Cell densities and colocalization with gut hormones were quantified and statistically compared.","limitations":"The study was conducted in pigs, so results may not fully translate to humans. The exact functional consequences of increased α-transducin and α-gustducin cells were not directly assessed. The study type and evidence strength were not specified."},{"rthcId":"RPEP-02911","title":"Impact of Duodenal-Jejunal Exclusion on Satiety Hormones.","authors":"de Jonge, Charlotte; Rensen, Sander S; Verdam, Froukje J; Vincent, Royce P; Bloom, Steve R; Buurman, Wim A; le Roux, Carel W; Bouvy, Nicole D; Greve, Jan Willem M","year":2016,"journal":"Obesity surgery, 26(3), 672-8","doi":"10.1007/s11695-015-1889-y","pmid":"26446491","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A duodenal-jejunal bypass liner (DJBL) — a non-surgical sleeve placed in the upper intestine — produced 12.7 kg weight loss over 24 weeks while significantly altering appetite-regulating peptide hormones. Postprandial PYY increased from 2.6 to 4.1 nmol/L/min (p<0.05) and ghrelin from 7.8 to 11.0 ng/mL/min (p<0.05) within the first week. CCK response decreased from 434 to 229 pmol/L/min (p<0.01). Fasting leptin dropped from 98 to 53 ng/mL (p<0.01). These hormonal changes occurred rapidly (within 1 week) and persisted through 24 weeks.","whyItMatters":"This study reveals how bypassing the upper intestine reprograms the body's appetite peptide signaling. The rapid increase in PYY (a satiety peptide) and decrease in CCK suggest the hormonal changes drive weight loss rather than simply resulting from it. Understanding how gut anatomy shapes peptide hormone responses could lead to targeted therapies that mimic these hormonal changes without surgery or devices.","specificNumbers":"n=17 · weight loss 4.3 kg at week 1, 12.7 kg at week 24 · PYY: 2.6→4.1→4.1 nmol/L/min · ghrelin: 7.8→11.0→10.6 ng/mL/min · CCK: 434→229→256 pmol/L/min · leptin: 98→53 ng/mL · all p<0.05 or better","methodology":"A two-center prospective study enrolled 17 obese adults with type 2 diabetes who received the DJBL for 24 weeks. Fasting leptin and postprandial responses of PYY, CCK, and ghrelin were measured before implantation and at weeks 1 and 24. Meal responses were quantified as area under the curve values.","limitations":"Small sample size (n=17) with no control group, making it impossible to distinguish device-specific hormonal effects from weight loss-mediated changes. The lack of randomization or sham-device control limits causal inference. The DJBL has since been withdrawn from the market in some regions due to safety concerns (liver abscess risk). Long-term hormonal effects beyond 24 weeks were not assessed."},{"rthcId":"RPEP-02912","title":"Efficacy and safety of liraglutide for overweight adult patients with type 1 diabetes and insufficient glycaemic control (Lira-1): a randomised, double-blind, placebo-controlled trial.","authors":"Dejgaard, Thomas Fremming; Frandsen, Christian Seerup; Hansen, Tanja Stenbæk; Almdal, Thomas; Urhammer, Søren; Pedersen-Bjergaard, Ulrik; Jensen, Tonny; Jensen, Andreas Kryger; Holst, Jens Juul; Tarnow, Lise; Knop, Filip Krag; Madsbad, Sten; Andersen, Henrik Ullits","year":2016,"journal":"The lancet. Diabetes & endocrinology, 4(3), 221-232","doi":"10.1016/S2213-8587(15)00436-2","pmid":"26656289","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The primary endpoint was not met: HbA1c change did not significantly differ between groups (-0.5% with liraglutide vs -0.3% with placebo; between-group difference -0.2%, p=0.18). However, several clinically meaningful secondary benefits emerged:\n\n- Body weight: -6.8 kg difference favoring liraglutide (p=0.015)\n- Bolus insulin: -5.8 IU difference (p=0.023)\n- Hypoglycemic events: 18% reduction (incident rate ratio 0.82, p<0.001)\n- Heart rate: +7.5 bpm increase with liraglutide (p=0.002)\n- Gastrointestinal side effects: nausea 58% vs 10%, dyspepsia 22% vs 2%\n\nGastric emptying was initially delayed at 3 weeks but normalized by 24 weeks.","whyItMatters":"Many people with type 1 diabetes are overweight and struggle with blood sugar control despite insulin. While liraglutide didn't improve HbA1c, the significant weight loss, insulin dose reduction, and fewer hypos are clinically meaningful. These findings help define where GLP-1 drugs might and might not help in type 1 diabetes — and set the stage for trials of newer GLP-1 drugs like semaglutide in this population.","specificNumbers":"","methodology":"Randomized, double-blind, placebo-controlled trial at Steno Diabetes Center, Denmark. 100 patients with type 1 diabetes (HbA1c >8%, BMI >25 kg/m²) were randomized 1:1 to liraglutide or placebo added to existing insulin. Liraglutide was escalated from 0.6 mg to 1.8 mg daily over 2+ weeks. Treatment lasted 24 weeks. Analysis used mixed models for efficacy in the modified ITT population.","limitations":"The sample size of 100 patients may have been insufficient to detect a modest HbA1c difference. The trial was only 24 weeks long. The high rate of GI side effects (58% nausea) may have affected adherence and could limit real-world applicability. The study was funded by Novo Nordisk, liraglutide's manufacturer. Only overweight patients with poor control were included, limiting generalizability."},{"rthcId":"RPEP-02913","title":"An Analysis of Neuropeptides at Nasal Contact Points of Patients With Secondary Headache.","authors":"Demir, Deniz; Cengiz, Nureddin; Güven, Mehmet; Bulduk, Oğuzhan","year":2016,"journal":"The Journal of craniofacial surgery, 27(3), e305-9","doi":"10.1097/SCS.0000000000002553","pmid":"27054429","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 20 patients with secondary headaches and nasal contact points, surgery produced significant headache reduction measured by visual analog scale at 3 months (p<0.001) and 12 months (p<0.001) postoperatively.\n\nHowever, fluorescein staining for substance P (p=0.631), neurokinin A (p=0.546), and CGRP (p=0.683) showed no statistically significant differences between contact mucosa and non-contact mucosa. This dissociation between clinical improvement and neuropeptide levels suggests the mechanism of headache relief from surgery involves factors other than local neuropeptide accumulation.","whyItMatters":"The relationship between nasal contact points and headaches has been debated for years. While this study confirms that surgery helps, it challenges the hypothesis that local neuropeptide accumulation at contact points drives the pain. This redirects researchers toward other mechanisms — such as mechanical pressure on trigeminal nerve endings — and helps set realistic expectations about neuropeptide-targeted nasal therapies.","specificNumbers":"","methodology":"This prospective study enrolled 20 adults with secondary headaches and nasal obstruction confirmed by endoscopy and CT scan. During corrective surgery, tissue samples were collected from both nasal contact points and non-contact areas. Neuropeptide intensity was measured using fluorescein-labeled antibodies against substance P, neurokinin A, and CGRP, analyzed with ImageJ software. Headache severity was assessed preoperatively and at 3 and 12 months post-surgery using a visual analog scale.","limitations":"The study had only 20 patients with no non-surgical control group, making it impossible to account for placebo effects of surgery. Neuropeptide levels were measured by immunofluorescence intensity rather than quantitative assays like ELISA, which may lack sensitivity. The study only measured neuropeptide presence in tissue, not release or dynamic changes during headache episodes. Follow-up was limited to 12 months."},{"rthcId":"RPEP-02914","title":"Cholecystokinin-induced satiety, a key gut servomechanism that is affected by the membrane microenvironment of this receptor.","authors":"Desai, A J; Dong, M; Harikumar, K G; Miller, L J","year":2016,"journal":"International journal of obesity supplements, 6(Suppl 1), S22-S27","doi":"10.1038/ijosup.2016.5","pmid":"28685026","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CCK induces satiety through activation of the CCK1 receptor, but receptor function is impaired by excess membrane cholesterol, a feature of metabolic syndrome. Positive allosteric modulators (PAMs) that enhance CCK1R activity without directly activating the receptor may offer a safer approach to obesity treatment by restoring receptor function and improving appetite regulation.","whyItMatters":"Understanding how cholesterol affects CCK receptor function could lead to better treatments for obesity by improving appetite control without the side effects associated with direct receptor agonists.","specificNumbers":"","methodology":"This study is a review of existing research on the molecular interactions of CCK with its receptor, the effects of membrane cholesterol on receptor function, and the potential of allosteric modulators to improve receptor activity for obesity management.","limitations":"As a review, the study does not present new experimental data and the effectiveness and safety of proposed modulators require further clinical validation."},{"rthcId":"RPEP-02915","title":"Improved clinical outcome and biomarkers in adults with papulopustular rosacea treated with doxycycline modified-release capsules in a randomized trial.","authors":"Di Nardo, Anna; Holmes, Anna D; Muto, Yumiko; Huang, Eugene Y; Preston, Norman; Winkelman, Warren J; Gallo, Richard L","year":2016,"journal":"Journal of the American Academy of Dermatology, 74(6), 1086-92","doi":"10.1016/j.jaad.2016.01.023","pmid":"26951940","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Doxycycline 40-mg modified-release capsules significantly reduced inflammatory lesions and improved investigator global assessment scores compared to placebo over 12 weeks. Cathelicidin expression and protein levels decreased during treatment. Low levels of protease activity and cathelicidin expression at 12 weeks correlated with treatment success. Low baseline protease activity predicted clinical response to doxycycline, suggesting it could serve as a predictive biomarker for treatment selection.","whyItMatters":"Cathelicidin is an antimicrobial peptide that plays a dual role — it protects against infection but drives inflammation when overproduced, as in rosacea. This study validates cathelicidin as both a disease mechanism and a trackable biomarker, demonstrating that reducing this peptide correlates with clinical improvement. This supports a precision medicine approach to rosacea treatment.","specificNumbers":"","methodology":"A multicenter, randomized, double-blind, placebo-controlled trial enrolled 170 adults with papulopustular rosacea. Participants received doxycycline 40-mg modified-release capsules or placebo for 12 weeks. Cathelicidin expression and protease activity were measured from stratum corneum tape strips and skin biopsies from a random subset. Clinical response was assessed by inflammatory lesion counts and investigator global assessment scores.","limitations":"Healthy control subjects were not studied, so baseline cathelicidin levels in unaffected skin were not compared. Skin biopsies were only obtained from a subset of participants. The 12-week duration may not capture long-term effects or relapse patterns. The study used sub-antimicrobial dose doxycycline, so results may not apply to higher antibiotic doses."},{"rthcId":"RPEP-02916","title":"Beyond anti-microbial properties: The role of cathelicidin in allergic rhinitis.","authors":"Dilek, F; Gultepe, B; Ozkaya, E; Yazici, M; Gedik, A H; Cakir, E","year":2016,"journal":"Allergologia et immunopathologia, 44(4), 297-302","doi":"10.1016/j.aller.2015.07.006","pmid":"26777417","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Children with allergic rhinitis had significantly lower nasal fluid LL-37 levels than healthy controls (median 2.3 ng/ml vs. 2.6 ng/ml, p<0.001). The levels were further reduced in moderate/severe AR compared to mild AR (2.2 ng/ml vs. 2.5 ng/ml, p<0.001). All AR patients were newly diagnosed and medication-free, eliminating treatment as a confounding factor.","whyItMatters":"Allergic rhinitis affects millions of children worldwide, and current treatments focus on symptom management rather than addressing underlying immune mechanisms. The finding that cathelicidin levels correlate inversely with disease severity suggests this antimicrobial peptide may have immunoregulatory functions in allergic inflammation. This could open new avenues for biomarker development (using LL-37 levels to assess severity) or therapeutic approaches that boost cathelicidin to modulate the allergic response.","specificNumbers":"","methodology":"This case-control study enrolled 46 children newly diagnosed with allergic rhinitis (medication-naive) and 33 healthy controls. Nasal secretions were collected using polyurethane sponge nasal secretion collectors, and LL-37 peptide levels were measured using ELISA (enzyme-linked immunosorbent assay). Disease severity was classified to compare LL-37 levels between mild and moderate/severe groups.","limitations":"This is a cross-sectional observational study, so it cannot determine whether low LL-37 causes allergic rhinitis or is a consequence of it. The sample size is modest (79 total children). The absolute differences in LL-37 levels, while statistically significant, are relatively small. The study did not measure other inflammatory markers or immune mediators that could help explain the mechanism. Nasal fluid collection methods can introduce variability."},{"rthcId":"RPEP-02917","title":"Esophagogastric anastomosis in rats: Improved healing by BPC 157 and L-arginine, aggravated by L-NAME.","authors":"Djakovic, Zeljko; Djakovic, Ivka; Cesarec, Vedran; Madzarac, Goran; Becejac, Tomislav; Zukanovic, Goran; Drmic, Domagoj; Batelja, Lovorka; Zenko Sever, Anita; Kolenc, Danijela; Pajtak, Alen; Knez, Nikica; Japjec, Mladen; Luetic, Kresimir; Stancic-Rokotov, Dinko; Seiwerth, Sven; Sikiric, Predrag","year":2016,"journal":"World journal of gastroenterology, 22(41), 9127-9140","doi":null,"pmid":"27895400","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BPC 157 administration fully prevented mortality and improved healing outcomes after esophagogastric anastomosis in rats. It counteracted the negative effects of L-NAME, a nitric oxide synthase blocker, and enhanced the beneficial effects of L-arginine, a nitric oxide precursor, indicating that BPC 157 acts via modulation of the NO system to promote tissue repair.","whyItMatters":"Improving healing after esophagogastric surgery is critical to prevent life-threatening complications. BPC 157's ability to enhance tissue repair and counteract nitric oxide system impairments offers a promising therapeutic approach for surgical recovery and gastrointestinal health.","specificNumbers":"","methodology":"Rats underwent esophagogastric anastomosis surgery and were treated daily with intraperitoneal doses of BPC 157 (10 μg or 10 ng/kg), L-NAME (5 mg/kg), L-arginine (100 mg/kg), or combinations thereof for 4 days. Healing was assessed by measuring stomach damage, esophagitis scores, anastomosis strength, sphincter pressure, weight loss, mortality, and blood vessel presence immediately after surgery.","limitations":"The study was conducted in rats, so results may not directly translate to humans. The exact molecular mechanisms of BPC 157's effects on the NO system require further investigation. The study type and evidence strength were not clearly defined."},{"rthcId":"RPEP-02918","title":"Glucagon-Like Peptide-1 Receptor Agonists for Type 2 Diabetes: A Clinical Update of Safety and Efficacy.","authors":"Drab, Scott R","year":2016,"journal":"Current diabetes reviews, 12(4), 403-413","doi":null,"pmid":"26694823","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 receptor agonists provide robust glycemic control, promote weight loss, and reduce blood pressure in patients with type 2 diabetes. Current studies do not confirm an increased risk of pancreatitis, pancreatic cancer, or thyroid cancer, but further research is necessary due to methodological limitations in existing studies.","whyItMatters":"Understanding the safety and effectiveness of GLP-1 receptor agonists helps clinicians make informed decisions about diabetes treatment. It also guides future research to clarify long-term risks and optimize patient care.","specificNumbers":"","methodology":"This is a literature review based on a MEDLINE search from 2010 to 2015, including efficacy and safety studies, pooled analyses, meta-analyses, and abstracts from major diabetes associations. The review prioritized longer-acting GLP-1 receptor agonists and examined their benefits and potential adverse events.","limitations":"The review relies on studies with methodological flaws and limited long-term data, making it difficult to draw firm conclusions about rare adverse events like cancer. The evidence strength and study types were not clearly defined."},{"rthcId":"RPEP-02919","title":"An Open Label Clinical Trial of a Peptide Treatment Serum and Supporting Regimen Designed to Improve the Appearance of Aging Facial Skin.","authors":"Draelos, Zoe Diana; Kononov, Tatiana; Fox, Theresa","year":2016,"journal":"Journal of drugs in dermatology : JDD, 15(9), 1100-6","doi":null,"pmid":"27602972","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The peptide treatment serum and supporting regimen produced statistically significant reductions in facial and eye wrinkles both at rest and during maximum smile, along with improvements in skin smoothness, softness, firmness, radiance, and overall appearance after 14 weeks of use.","whyItMatters":"This study supports the potential of peptide-based topical treatments to improve visible signs of skin aging, which is important for developing effective anti-aging skincare products.","specificNumbers":"","methodology":"An open-label, single-center clinical usage study was conducted over 14 weeks involving 29 women with mild to moderate photodamaged facial skin. Expert investigators assessed facial lines and wrinkles at rest and maximum smile, supplemented by participant self-assessments.","limitations":"The study was open-label without a placebo control group, and the sample size was relatively small, which may limit the generalizability of the findings."},{"rthcId":"RPEP-02920","title":"The Cardiovascular Biology of Glucagon-like Peptide-1.","authors":"Drucker, Daniel J","year":2016,"journal":"Cell metabolism, 24(1), 15-30","doi":"10.1016/j.cmet.2016.06.009","pmid":"27345422","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 receptor agonists influence cardiovascular health by modulating inflammation and cardiovascular physiology, thereby reducing the risk of cardiovascular complications in diabetic patients. Both animal and human studies demonstrate that GLP-1R signaling provides direct and indirect cardiovascular benefits.","whyItMatters":"Understanding how GLP-1 peptides affect the heart and blood vessels can improve treatments for diabetes-related cardiovascular disease, a leading cause of death worldwide. This knowledge supports the development of therapies that address both metabolic and cardiovascular health.","specificNumbers":"","methodology":"This is a comprehensive review of existing animal and human studies examining the cardiovascular effects of GLP-1 and GLP-1 receptor agonists, summarizing mechanisms and clinical outcomes related to cardiovascular disease risk modification.","limitations":"As a review, the study relies on previously published data with varying study designs and populations, which may limit the ability to draw definitive conclusions about causality and long-term effects."},{"rthcId":"RPEP-02921","title":"Evidence for involvement of NK₃ receptors in the anxiogenic-like effect of SP6-11(C-terminal), a metabolite of substance P, in rats evaluated in the elevated plus-maze.","authors":"Duarte, Filipe Silveira; Duzzioni, Marcelo; Leme, Leandro Rinaldi; Smith, Saulo de Paiva; De Lima, Thereza C M","year":2016,"journal":"Behavioural brain research, 303, 168-75","doi":"10.1016/j.bbr.2016.02.003","pmid":"26851555","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"SP6-11(C-terminal), a metabolite of substance P, induces anxiogenic-like effects in rats by acting as an antagonist at NK3 receptors. Blocking NK3 receptors with SR142801 mimicked SP6-11's anxiety effects, while activating NK3 receptors with senktide produced anxiolytic-like effects. SP6-11 also prevented the anxiolytic effect of senktide, supporting NK3 receptor involvement.","whyItMatters":"This study identifies NK3 receptors as key players in anxiety-related effects of substance P metabolites, offering potential targets for developing new anxiety treatments or understanding neuropeptide roles in fear processing.","specificNumbers":"","methodology":"Adult male Wistar rats received intracerebroventricular injections of SP6-11(C-terminal), NK3 receptor antagonist SR142801, or NK3 receptor agonist senktide in various combinations. Anxiety-like behavior was assessed five minutes later using the elevated plus-maze test, which measures exploration of open arms and protective behaviors.","limitations":"The study was conducted only in male rats with intracerebroventricular injections, limiting direct applicability to humans or other administration routes. The exact molecular mechanisms remain to be fully elucidated."},{"rthcId":"RPEP-02922","title":"Challenges in Targeting a Basic Helix-Loop-Helix Transcription Factor with Hydrocarbon-Stapled Peptides.","authors":"Edwards, Amanda L; Meijer, Dimphna H; Guerra, Rachel M; Molenaar, Remco J; Alberta, John A; Bernal, Federico; Bird, Gregory H; Stiles, Charles D; Walensky, Loren D","year":2016,"journal":"ACS chemical biology, 11(11), 3146-3153","doi":null,"pmid":"27643505","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A library of stabilized α-helices of OLIG2 (SAH-OLIG2) was developed using hydrocarbon stapling of varying lengths and sequences. Key findings:\n\n• Stapling successfully reinforced the α-helical structure of all bHLH constructs tested\n• Despite structural stabilization, sequence-specific dissociation of OLIG2 dimers from DNA was not achieved\n• Re-evaluation of binding determinants revealed an unanticipated role of the C-terminal domain in OLIG2 self-association and stability\n• The positively charged amino acid sequences inherent to bHLH domains created liabilities for peptide-based targeting\n• The multifactorial binding determinants of OLIG2 (not just the helix-loop-helix region) complicate the decoy peptide approach","whyItMatters":"Stapled peptides represent one of the most promising approaches in peptide drug design, having shown success against targets like BCL-2 family proteins. This study reveals important limitations when applying the same strategy to transcription factors, a notoriously difficult drug target class. Understanding why stapled peptides fail against certain targets is as valuable as understanding when they succeed — it guides the field toward better design strategies.","specificNumbers":"","methodology":"The researchers designed and synthesized a library of hydrocarbon-stapled peptides based on OLIG2 bHLH domain sequences of varying lengths. Peptides were tested for α-helical content, ability to disrupt OLIG2 homodimerization, and capacity to dissociate OLIG2 from DNA using biochemical assays. Binding determinant analysis was performed to understand why the peptides failed, leading to the discovery of the C-terminal domain's role.","limitations":"The study reports a negative result — the stapled peptides did not achieve functional disruption. While this is scientifically valuable, the specific reasons for failure (charge, multifactorial binding) may be particular to OLIG2 and not generalizable to all bHLH targets. Only biochemical assays were used; cell-based and in vivo experiments were not described. The C-terminal domain's contribution was revealed post hoc rather than predicted."},{"rthcId":"RPEP-02923","title":"Is really endogenous ghrelin a hunger signal in chickens? Association of GHSR SNPs with increase appetite, growth traits, expression and serum level of GHRL, and GH.","authors":"El-Magd, Mohammed Abu; Saleh, Ayman A; Abdel-Hamid, Tamer M; Saleh, Rasha M; Afifi, Mohammed A","year":2016,"journal":"General and comparative endocrinology, 237, 131-139","doi":"10.1016/j.ygcen.2016.08.016","pmid":"27591070","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Two single nucleotide polymorphisms (SNPs) in the GHSR gene, particularly the non-synonymous G244A mutation, were associated with increased appetite, enhanced growth traits, and elevated mRNA and serum levels of GHSR, GHRL, and GH in Mandara chickens. Chickens homozygous for the GG/GG haplotype exhibited significantly higher growth performance and hormone expression.","whyItMatters":"Understanding how genetic variations affect hunger and growth hormones in chickens can improve breeding strategies for better growth performance and feed efficiency. It also clarifies the role of endogenous ghrelin as a hunger signal in avian species.","specificNumbers":"","methodology":"The study identified SNPs in exon 2 of the GHSR gene in Mandara chickens and analyzed their association with appetite, growth traits, gene expression (GHSR, GHRL, GH), and serum hormone levels. Genotyping and mRNA expression analyses were conducted alongside measurements of serum GH and GHRL levels.","limitations":"The study did not specify the sample size or provide detailed evidence strength, limiting the generalizability of the findings. Also, the functional impact of the SNPs was inferred but not directly tested in vivo or through receptor activity assays."},{"rthcId":"RPEP-02924","title":"Substance P Activates Ca2+-Permeable Nonselective Cation Channels through a Phosphatidylcholine-Specific Phospholipase C Signaling Pathway in nNOS-Expressing GABAergic Neurons in Visual Cortex.","authors":"Endo, Toshiaki; Yanagawa, Yuchio; Komatsu, Yukio","year":2016,"journal":"Cerebral cortex (New York, N.Y. : 1991), 26(2), 669-682","doi":"10.1093/cercor/bhu233","pmid":"25316339","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Substance P activates Ca2+-permeable nonselective cation channels in nNOS-expressing GABAergic neurons of the visual cortex via a phosphatidylcholine-specific phospholipase C (PC-PLC) signaling pathway, involving TRP-like channels and G protein mediation.","whyItMatters":"Understanding how substance P modulates calcium channels in inhibitory neurons provides insight into cortical circuit regulation and could inform therapeutic strategies targeting neuropeptide signaling in brain disorders.","specificNumbers":"","methodology":"Using visual cortical slices from genetically modified mice, the researchers applied substance P and recorded ionic currents and calcium levels in identified nNOS-positive GABAergic neurons. Pharmacological blockers were used to dissect the signaling pathway involved.","limitations":"The study was conducted in brain slices from young mice, which may not fully represent in vivo adult brain conditions; the exact physiological role of this pathway remains to be established."},{"rthcId":"RPEP-02925","title":"Collagencin, an antibacterial peptide from fish collagen: Activity, structure and interaction dynamics with membrane.","authors":"Ennaas, Nadia; Hammami, Riadh; Gomaa, Ahmed; Bédard, François; Biron, Éric; Subirade, Muriel; Beaulieu, Lucie; Fliss, Ismail","year":2016,"journal":"Biochemical and biophysical research communications, 473(2), 642-7","doi":"10.1016/j.bbrc.2016.03.121","pmid":"27038545","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Collagencin completely inhibited Staphylococcus aureus growth at 1.88 mM concentration. The peptide adopts β-sheet and β-turn structures and interacts with both anionic and zwitterionic membrane lipids, suggesting a carpet-like mechanism of antibacterial action. It is non-toxic up to 470 μM but exhibits hemolytic activity at higher concentrations.","whyItMatters":"This research identifies a novel antimicrobial peptide from fish collagen, highlighting a potential new source for natural antibacterial agents. Such peptides could be valuable in developing new treatments or food safety applications.","specificNumbers":"","methodology":"The study characterized collagencin using circular dichroism spectroscopy and molecular dynamics simulations to determine its structure and membrane interactions. Antibacterial activity was tested against Staphylococcus aureus, and toxicity was assessed via hemolysis assays.","limitations":"The study did not specify the full range of bacterial strains tested or in vivo efficacy. Toxicity at higher doses may limit therapeutic use without further modification."},{"rthcId":"RPEP-02926","title":"Angiogenesis Imaging Using (68)Ga-RGD PET/CT: Therapeutic Implications.","authors":"Eo, Jae Seon; Jeong, Jae Min","year":2016,"journal":"Seminars in nuclear medicine, 46(5), 419-27","doi":"10.1053/j.semnuclmed.2016.04.001","pmid":"27553467","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02927","title":"Gastrointestinal Physiological Changes and Their Relationship to Weight Loss Following the POSE Procedure.","authors":"Espinós, J C; Turró, R; Moragas, G; Bronstone, A; Buchwald, J N; Mearin, F; Mata, A; Uchima, H; Turró, J; Delgado-Aros, S","year":2016,"journal":"Obesity surgery, 26(5), 1081-9","doi":"10.1007/s11695-015-1863-8","pmid":"26337693","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"POSE resulted in a mean total weight loss of 19.1% and excess weight loss of 63.7% at 15 months. The procedure decreased intake capacity significantly and altered gastric emptying and gut hormone responses, including increased postprandial PYY and enhanced ghrelin suppression, which were associated with weight loss.","whyItMatters":"Understanding how POSE induces weight loss through gut physiology and hormone changes can improve bariatric treatments and guide development of less invasive obesity therapies.","specificNumbers":"","methodology":"Eighteen patients with class I-II obesity underwent the POSE procedure. They were evaluated at baseline, 2, and 6 months for gastric emptying, intake capacity, and gut hormone levels, with weight tracked through 15 months. Regression models identified factors predicting weight loss.","limitations":"Small sample size (18 patients) and lack of a control group limit generalizability. The study design and evidence strength were not clearly defined."},{"rthcId":"RPEP-02928","title":"A systematic review of the safety of incretin-based therapies in type 2 diabetes.","authors":"Evans, Marc; Bain, Stephen C; Vora, Jiten","year":2016,"journal":"Expert review of endocrinology & metabolism, 11(2), 217-232","doi":"10.1586/17446651.2015.1057502","pmid":"30058866","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Incretin-based therapies, including DPP-4 inhibitors and GLP-1 receptor agonists, demonstrated lower hypoglycemia rates compared to other antidiabetic drugs and insulin. Common adverse events included infections for DPP-4 inhibitors and gastrointestinal issues for GLP-1 receptor agonists. Pancreatitis was rare and cardiovascular risk was not increased in major trials over short follow-up periods.","whyItMatters":"Understanding the safety of incretin-based therapies helps clinicians and patients make informed treatment decisions and supports the continued development of effective diabetes medications with minimal side effects.","specificNumbers":"","methodology":"This systematic review analyzed 112 randomized clinical trials lasting at least 26 weeks, published between 2000 and 2015, involving patients with type 2 diabetes to assess the safety profile of incretin-based therapies.","limitations":"The review includes trials with varying durations and follow-up periods, some relatively short, limiting conclusions about long-term safety. Evidence strength and study types were not specified."},{"rthcId":"RPEP-02929","title":"Arrival by ambulance in acute heart failure: insights into the mode of presentation from Acute Studies of Nesiritide in Decompensated Heart Failure (ASCEND-HF).","authors":"Ezekowitz, Justin A; Podder, Mohua; Hernandez, Adrian F; Armstrong, Paul W; Starling, Randall C; O'Connor, Christopher M; Califf, Robert M","year":2016,"journal":"BMJ open, 6(3), e010201","doi":"10.1136/bmjopen-2015-010201","pmid":"26988350","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02930","title":"LL-37: Cathelicidin-related antimicrobial peptide with pleiotropic activity.","authors":"Fabisiak, Adam; Murawska, Natalia; Fichna, Jakub","year":2016,"journal":"Pharmacological reports : PR, 68(4), 802-8","doi":"10.1016/j.pharep.2016.03.015","pmid":"27117377","tags":[],"studyType":"review","evidenceStrength":"expert-opinion","keyFinding":"This review establishes LL-37 as far more than an antimicrobial peptide. As the sole human cathelicidin, LL-37 serves as a broad-spectrum natural antibiotic, but also has potent chemotactic properties (attracting immune cells to sites of infection) and immunomodulatory effects. The authors analyzed LL-37’s therapeutic potential across four major systems: immune, respiratory, gastrointestinal, and skin — identifying specific molecular pathways and disease connections in each.","whyItMatters":"LL-37 is unique in human biology as the only cathelicidin we produce, yet it wears many hats — antimicrobial, immune signaling, wound healing, and inflammation modulation. This review maps those diverse functions to specific diseases and molecular pathways, making a comprehensive case for developing LL-37-based therapeutics that could address conditions ranging from infections to inflammatory bowel disease to skin disorders.","specificNumbers":"4 body systems reviewed (immune, respiratory, GI, skin) · sole human cathelicidin · broad-spectrum antimicrobial activity","methodology":"Comprehensive literature review analyzing published research on LL-37’s molecular mechanisms, biological activities, and therapeutic potential across immune, respiratory, gastrointestinal, and skin systems. No original experimental data were generated.","limitations":"This is a narrative review without new experimental data. The therapeutic potential discussed remains largely preclinical, and the gap between LL-37’s known biology and its clinical development as a drug is not fully addressed. The review does not systematically assess evidence quality."},{"rthcId":"RPEP-02931","title":"Inspiration from the mirror: D-amino acid containing peptides in biomedical approaches.","authors":"Feng, Zhaoqianqi; Xu, Bing","year":2016,"journal":"Biomolecular concepts, 7(3), 179-87","doi":"10.1515/bmc-2015-0035","pmid":"27159920","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"D-amino acid incorporation into peptides provides resistance to enzymatic degradation, significantly extending their biostability. The review covers three key applications: (1) traditional use of D-amino acid substitution to make peptide drugs last longer in the body, (2) mirror-image phage display and retro-inverso synthesis to discover all-D-amino acid peptide therapeutics, and (3) an emerging application — enzyme-instructed self-assembly (EISA) — where D-amino acid peptides selectively form nanostructures inside specific cells (cancer cells or inflammatory cells) to kill them.","whyItMatters":"One of the biggest problems with peptide drugs is that they break down quickly in the body — digestive enzymes and blood proteases destroy them within minutes. D-amino acids are the mirror image of natural L-amino acids, and enzymes can't recognize them properly. Swapping even a few L-amino acids for D-amino acids can dramatically extend a peptide drug's half-life. The newer EISA applications are even more exciting: D-peptides can be designed to self-assemble into toxic nanostructures only inside cancer cells, creating a targeted therapy.","specificNumbers":"D-amino acids = mirror images of natural L-amino acids · Resist enzymatic degradation · Applications: biostability, mirror-image phage display, retro-inverso peptides, EISA","methodology":"Narrative review article covering recent literature on D-amino acid applications in biomedical research, including peptide drug development, mirror-image phage display, retro-inverso peptide synthesis, and enzyme-instructed self-assembly (EISA) applications.","limitations":"This is a review of a broad field, not a single experimental study. The EISA applications described were mostly at early research stages at the time of publication. The review focuses on the advantages of D-amino acids without extensively discussing challenges like increased manufacturing cost, potential immunogenicity of D-peptides, or difficulty predicting D-peptide activity from L-peptide data."},{"rthcId":"RPEP-02932","title":"Do Substance P and Neurokinin A Play Important Roles in the Control of LH Secretion in Ewes?","authors":"Fergani, Chrysanthi; Mazzella, Leanne; Coolen, Lique M; McCosh, Richard B; Hardy, Steven L; Newcomb, Nora; Grachev, Pasha; Lehman, Michael N; Goodman, Robert L","year":2016,"journal":"Endocrinology, 157(12), 4829-4841","doi":null,"pmid":"27704950","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Neurokinin B acting via the neurokinin-3 receptor (NK3R) is the primary tachykinin pathway stimulating GnRH and LH secretion in ewes. Substance P and neurokinin A, which act via NK1R and NK2R respectively, have significantly lower potency and minimal coexpression with kisspeptin or GnRH neurons.","whyItMatters":"Understanding which peptides regulate reproductive hormones in sheep helps clarify the neurochemical control of fertility and may inform treatments for reproductive disorders or improve livestock breeding strategies.","specificNumbers":"","methodology":"The study used immunohistochemistry to map substance P and NK1R expression in the sheep brain and examined colocalization with kisspeptin and GnRH neurons. It also tested the effects of administering neurokinin B, substance P, and neurokinin A into the third ventricle of anestrous sheep to measure LH secretion responses.","limitations":"The study was conducted in ovary-intact anestrous sheep, which may limit generalization to other reproductive states or species. The exact mechanisms by which substance P and neurokinin A influence LH secretion remain unclear."},{"rthcId":"RPEP-02933","title":"Design and Development of a Cyclic Decapeptide Scaffold with Suitable Properties for Bioavailability and Oral Exposure.","authors":"Fouché, Marianne; Schäfer, Michael; Berghausen, Jörg; Desrayaud, Sandrine; Blatter, Markus; Piéchon, Philippe; Dix, Ina; Martin Garcia, Aimar; Roth, Hans-Jörg","year":2016,"journal":"ChemMedChem, 11(10), 1048-59","doi":"10.1002/cmdc.201600082","pmid":"27154275","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The study successfully designed a cyclic decapeptide scaffold with a rigid β-hairpin structure incorporating d-proline at the i+1 turn position, resulting in significantly improved oral bioavailability and cell permeability. NMR analysis confirmed scaffold rigidity and transannular hydrogen bonding, which contribute to enhanced membrane permeation and reduced clearance.","whyItMatters":"This work addresses key challenges in delivering macrocyclic peptide drugs orally, potentially expanding their therapeutic use beyond intravenous administration. Improving oral bioavailability and cell permeability can make peptide drugs more convenient and effective for patients.","specificNumbers":"","methodology":"The researchers designed cyclic decapeptides with a rigid β-hairpin conformation and introduced d-proline to stabilize the structure. They used NMR spectroscopy to analyze conformation and dynamics in different environments and evaluated permeability, clearance, and oral bioavailability properties.","limitations":"The study does not specify the exact oral bioavailability percentages or provide in vivo efficacy data. The evidence strength and study type are not detailed, limiting assessment of clinical relevance."},{"rthcId":"RPEP-02934","title":"Urinary and plasma oxytocin changes in response to MDMA or intranasal oxytocin administration.","authors":"Francis, Sunday M; Kirkpatrick, Matthew G; de Wit, Harriet; Jacob, Suma","year":2016,"journal":"Psychoneuroendocrinology, 74, 92-100","doi":"10.1016/j.psyneuen.2016.08.011","pmid":"27592327","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Administration of MDMA and intranasal oxytocin significantly increased plasma and urinary oxytocin levels. A positive correlation between urinary and plasma oxytocin was observed following MDMA and intranasal oxytocin in some conditions, but not consistently across all conditions.","whyItMatters":"Understanding how oxytocin levels change in blood and urine after drug administration helps improve non-invasive hormone measurement methods and informs research on social behavior and psychiatric disorders.","specificNumbers":"","methodology":"Two double-blind, within-subject studies were conducted. Study 1 involved 14 adults receiving oral MDMA (1.5 mg/kg) or 40 IU intranasal oxytocin across sessions, with blood and urine samples collected pre- and post-administration. Study 2 involved 10 males with autism spectrum disorder receiving 40 IU intranasal oxytocin or placebo, with similar sampling.","limitations":"Small sample sizes and limited time windows for measuring oxytocin may affect the generalizability and interpretation of the correlation between urine and plasma levels."},{"rthcId":"RPEP-02935","title":"Plasma and CSF oxytocin levels after intranasal and intravenous oxytocin in awake macaques.","authors":"Freeman, Sara M; Samineni, Sridhar; Allen, Philip C; Stockinger, Diane; Bales, Karen L; Hwa, Granger G C; Roberts, Jeffrey A","year":2016,"journal":"Psychoneuroendocrinology, 66, 185-94","doi":"10.1016/j.psyneuen.2016.01.014","pmid":"26826355","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Intravenous oxytocin administration produced a dose-dependent increase in plasma oxytocin levels, peaking at 5 minutes and returning to baseline by 120 minutes. Cerebrospinal fluid (CSF) oxytocin increased only at the highest intravenous dose (5 IU/kg) at 15 minutes post-dose. Intranasal oxytocin did not significantly change plasma levels at any dose but increased CSF oxytocin at the highest dose between 15-30 minutes post-dose.","whyItMatters":"Understanding how oxytocin reaches the brain after different administration routes is crucial for developing effective treatments for social disorders like autism. This study provides important pharmacokinetic data in a primate model closely related to humans.","specificNumbers":"","methodology":"Four female rhesus macaques with implanted intrathecal catheters underwent a randomized crossover study receiving oxytocin via intravenous and intranasal routes at three doses (0.1, 1, and 5 IU/kg). Concurrent plasma and CSF samples were collected over time to measure oxytocin levels.","limitations":"The study involved only four female monkeys, limiting generalizability. The exact translation of doses and effects to humans remains uncertain. The study did not assess behavioral outcomes."},{"rthcId":"RPEP-02936","title":"Overlapping expression of serotonin transporters and neurokinin-1 receptors in posttraumatic stress disorder: a multi-tracer PET study.","authors":"Frick, A; Åhs, F; Palmquist, Å M; Pissiota, A; Wallenquist, U; Fernandez, M; Jonasson, M; Appel, L; Frans, Ö; Lubberink, M; Furmark, T; von Knorring, L; Fredrikson, M","year":2016,"journal":"Molecular psychiatry, 21(10), 1400-7","doi":"10.1038/mp.2015.180","pmid":"26619809","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"PTSD patients exhibited increased neurokinin-1 receptor availability but not serotonin transporter availability in the amygdala. The overlap between serotonin transporter (SERT) and neurokinin-1 (NK1) receptor expression was reduced in several brain regions and correlated with higher PTSD symptom severity, indicating that interactions between these systems contribute to PTSD pathophysiology.","whyItMatters":"Understanding how serotonin and neurokinin-1 receptor systems interact in PTSD can reveal new targets for treatment. Normalizing these neurochemical interactions may improve therapies for anxiety and stress-related disorders.","specificNumbers":"","methodology":"The study used positron emission tomography (PET) imaging with selective radiotracers to measure serotonin transporter and NK1 receptor availability in 16 PTSD patients and 16 healthy controls. Voxel-wise analyses focused on the amygdala and whole-brain regions to assess receptor expression and overlap.","limitations":"The study had a small sample size and cross-sectional design, limiting the ability to determine causality. The evidence strength and study type were not clearly defined."},{"rthcId":"RPEP-02937","title":"Growth Hormone-Releasing Hormone in Diabetes.","authors":"Fridlyand, Leonid E; Tamarina, Natalia A; Schally, Andrew V; Philipson, Louis H","year":2016,"journal":"Frontiers in endocrinology, 7, 129","doi":null,"pmid":"27777568","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GHRH receptors are expressed on pancreatic beta-cells, and GHRH agonists can directly stimulate insulin secretion through signaling pathways similar to those used in the pituitary gland. Engineered GHRH analogs have been shown to:\n\n- Increase insulin secretion from isolated pancreatic islets\n- Preserve beta-cell function and survival\n- Potentially improve glucose metabolism in type 2 diabetes\n- Provide additional benefits including wound healing and cardioprotection\n\nThe review proposes that GHRH agonists could serve a dual role: improving insulin secretion while also protecting against diabetic complications like poor wound healing and cardiovascular damage.","whyItMatters":"Type 2 diabetes is fundamentally a disease of beta-cell failure — the insulin-producing cells gradually lose function over time. Most current diabetes drugs manage symptoms (blood sugar) rather than protecting the beta-cells themselves. If GHRH analogs can truly preserve beta-cell function and survival while also stimulating insulin secretion, they would address the root cause of the disease — a fundamentally different approach from existing treatments.","specificNumbers":"","methodology":"This is a review article that synthesizes research on GHRH receptor expression in peripheral tissues, particularly pancreatic islets. It examines preclinical studies on engineered GHRH agonists and antagonists, their signaling pathways in beta-cells, and their potential interactions with glucose-dependent insulin secretion mechanisms.","limitations":"The evidence presented is primarily from preclinical studies — isolated pancreatic islets and animal models. No human clinical trials of GHRH analogs specifically for diabetes treatment are described. The long-term effects and safety of chronically stimulating GHRH receptors on beta-cells are unknown. There is also concern about potential off-target growth-promoting effects of GHRH agonists, which would need careful evaluation."},{"rthcId":"RPEP-02938","title":"Nanoparticles Encapsulated with LL37 and Serpin A1 Promotes Wound Healing and Synergistically Enhances Antibacterial Activity.","authors":"Fumakia, Miral; Ho, Emmanuel A","year":2016,"journal":"Molecular pharmaceutics, 13(7), 2318-31","doi":"10.1021/acs.molpharmaceut.6b00099","pmid":"27182713","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A novel solid lipid nanoparticle formulation co-delivering LL37 and Serpin A1 at synergistic ratios significantly accelerated wound closure in fibroblast and keratinocyte cells and enhanced antibacterial activity against Staphylococcus aureus and Escherichia coli compared to individual treatments.","whyItMatters":"This approach addresses challenges in chronic wound treatment by providing controlled, sustained delivery of therapeutic peptides that both promote healing and combat infection, potentially reducing reliance on toxic antibiotics.","specificNumbers":"","methodology":"The study developed solid lipid nanoparticles encapsulating LL37 and Serpin A1 at specific ratios. In vitro experiments assessed wound closure in BJ fibroblast and keratinocyte cells and antibacterial efficacy against S. aureus and E. coli, comparing combined treatment to single agents.","limitations":"The study was conducted in vitro, so results may not fully translate to clinical wound healing in humans; the study type and evidence strength were not specified."},{"rthcId":"RPEP-02939","title":"Growth hormone-releasing hormone receptor antagonists inhibit human gastric cancer through downregulation of PAK1-STAT3/NF-κB signaling.","authors":"Gan, Jinfeng; Ke, Xiurong; Jiang, Jiali; Dong, Hongmei; Yao, Zhimeng; Lin, Yusheng; Lin, Wan; Wu, Xiao; Yan, Shumei; Zhuang, Yixuan; Chu, Wai Kit; Cai, Renzhi; Zhang, Xianyang; Cheung, Herman S; Block, Norman L; Pang, Chi Pui; Schally, Andrew V; Zhang, Hao","year":2016,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 113(51), 14745-14750","doi":"10.1073/pnas.1618582114","pmid":"27930339","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Survival analysis across multiple cohorts of gastric cancer patients established that increased GHRH receptor expression in tumor tissue independently predicts poor survival. The GHRH receptor antagonist MIA-602 effectively inhibited gastric cancer cell growth in vitro across multiple human cell lines.\n\nThese results were confirmed in vivo using xenograft mouse models with human gastric cancer cells. Mechanistically, MIA-602 targets the GHRH receptor and downregulates the PAK1-mediated STAT3/NF-κB inflammatory pathway, providing a clear molecular explanation for its anticancer effects.","whyItMatters":"Gastric cancer is the fourth most common cancer and second deadliest worldwide, yet effective targeted therapies remain limited. This study published in PNAS establishes the GHRH receptor as both a prognostic biomarker and therapeutic target. The peptide-based antagonist approach is particularly notable because it targets a specific receptor-pathway axis, potentially offering more precision than standard chemotherapy with fewer side effects.","specificNumbers":"","methodology":"The study combined clinical and preclinical approaches. Survival analyses of multiple gastric cancer patient cohorts correlated GHRH receptor expression with prognosis. In vitro experiments tested MIA-602's effects on human gastric cancer cell line growth. In vivo efficacy was confirmed using multiple human gastric cancer cell line xenografts in nude mice. Molecular pathway analysis identified PAK1-STAT3/NF-κB as the downstream signaling mechanism affected by GHRH receptor antagonism.","limitations":"The clinical survival data is retrospective and correlational — it shows GHRH-R expression predicts poor outcomes but does not prove causation. The in vivo work used immunodeficient nude mice with xenografts, which do not recapitulate the human immune response to cancer. No human clinical trials of MIA-602 for gastric cancer are reported. Specific tumor inhibition percentages and MIA-602 dosing details were not provided in the abstract. The study dates to 2016, and clinical translation progress is unclear."},{"rthcId":"RPEP-02940","title":"Role of thymosin beta 4 in hair growth.","authors":"Gao, Xiao-Yu; Hou, Fang; Zhang, Zhi-Peng; Nuo, Ming-Tu; Liang, Hao; Cang, Ming; Wang, Zhi-Gang; Wang, Xin; Xu, Teng; Yan, Le-Yan; Guo, Xu-Dong; Liu, Dong-Jun","year":2016,"journal":"Molecular genetics and genomics : MGG, 291(4), 1639-46","doi":"10.1007/s00438-016-1207-y","pmid":"27130465","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02941","title":"AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY COMPREHENSIVE CLINICAL PRACTICE GUIDELINES FOR MEDICAL CARE OF PATIENTS WITH OBESITY.","authors":"Garvey, W Timothy; Mechanick, Jeffrey I; Brett, Elise M; Garber, Alan J; Hurley, Daniel L; Jastreboff, Ania M; Nadolsky, Karl; Pessah-Pollack, Rachel; Plodkowski, Raymond","year":2016,"journal":"Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists, 22 Suppl 3, 1-203","doi":"10.4158/EP161365.GL","pmid":"27219496","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The guidelines present 160 specific recommendations for obesity care, with over 80% supported by strong or intermediate scientific evidence. They emphasize treating obesity as an adiposity-based chronic disease, targeting both weight and related health complications through individualized medical approaches.","whyItMatters":"Obesity is a major health challenge worldwide, and these guidelines help clinicians apply the best available evidence to improve patient outcomes. They provide a structured framework for integrating medical, behavioral, and therapeutic strategies in obesity care.","specificNumbers":"","methodology":"These guidelines were developed by the American Association of Clinical Endocrinologists and the American College of Endocrinology following standardized protocols. They involved a comprehensive review of 1,790 scientific references and incorporated both objective evidence and expert consensus to formulate clinical practice recommendations.","limitations":"The guideline's evidence strength and study types are not fully specified, and some recommendations rely on expert opinion due to limited high-quality data. Implementation may vary depending on healthcare settings and patient populations."},{"rthcId":"RPEP-02942","title":"pMPES: A Modular Peptide Expression System for the Delivery of Antimicrobial Peptides to the Site of Gastrointestinal Infections Using Probiotics.","authors":"Geldart, Kathryn; Forkus, Brittany; McChesney, Evelyn; McCue, Madeline; Kaznessis, Yiannis N","year":2016,"journal":"Pharmaceuticals (Basel, Switzerland), 9(4)","doi":null,"pmid":"27782051","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02943","title":"Cardiovascular outcomes of sodium-glucose cotransporter 2 inhibitors: A comprehensive review of clinical and preclinical studies.","authors":"Ghosh, Raktim Kumar; Bandyopadhyay, Dhrubajyoti; Hajra, Adrija; Biswas, Monodeep; Gupta, Anjan","year":2016,"journal":"International journal of cardiology, 212, 29-36","doi":"10.1016/j.ijcard.2016.02.134","pmid":"27017118","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"SGLT2 inhibitors, including dapagliflozin, canagliflozin, and empagliflozin, demonstrate cardiovascular benefits beyond glucose lowering, such as weight loss, blood pressure reduction, and renal protection. Notably, empagliflozin showed significant reductions in cardiovascular morbidity and mortality in the EMPA-REG OUTCOME trial.","whyItMatters":"Understanding the cardiovascular effects of SGLT2 inhibitors is vital for improving diabetes treatment strategies and reducing heart disease risk in diabetic patients.","specificNumbers":"","methodology":"This study is a comprehensive review of existing clinical and preclinical studies examining cardiovascular outcomes associated with SGLT2 inhibitors, including data from completed and ongoing major clinical trials.","limitations":"The review notes limited cardiovascular outcome data for SGLT2 inhibitors at the time, with ongoing trials needed to confirm long-term benefits and safety."},{"rthcId":"RPEP-02944","title":"Link Between Increased Satiety Gut Hormones and Reduced Food Reward After Gastric Bypass Surgery for Obesity.","authors":"Goldstone, Anthony P; Miras, Alexander D; Scholtz, Samantha; Jackson, Sabrina; Neff, Karl J; Pénicaud, Luc; Geoghegan, Justin; Chhina, Navpreet; Durighel, Giuliana; Bell, Jimmy D; Meillon, Sophie; le Roux, Carel W","year":2016,"journal":"The Journal of clinical endocrinology and metabolism, 101(2), 599-609","doi":"10.1210/jc.2015-2665","pmid":"26580235","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Postprandial increases in satiety gut hormones peptide YY (PYY), glucagon-like peptide-1 (GLP-1), and fibroblast growth factor-19 (FGF-19) after Roux-en-Y gastric bypass (RYGB) surgery reduce food reward and brain reward system activation. Acute suppression of these hormones with octreotide increased food reward behavior and brain responses in RYGB patients but not in controls.","whyItMatters":"Understanding how gut hormones influence food reward after gastric bypass can help develop new treatments for obesity that mimic surgery effects without invasive procedures. It highlights the hormonal control of appetite and food motivation.","specificNumbers":"","methodology":"Randomized, placebo-controlled, double-blind, crossover studies were conducted involving RYGB patients, gastric banding patients, and nonobese controls. Participants received octreotide or saline to suppress gut hormones, followed by behavioral food reward tasks and functional MRI to assess brain responses to food stimuli.","limitations":"Small sample sizes limit generalizability, and the acute hormone suppression may not fully represent long-term effects. The study design cannot prove causality definitively."},{"rthcId":"RPEP-02945","title":"Altered expression of the tachykinins substance P/neurokinin A/hemokinin-1 and their preferred neurokinin 1/neurokinin 2 receptors in uterine leiomyomata.","authors":"González-Santana, Ayoze; Marrero-Hernández, Sara; Dorta, Idaira; Hernández, Mariano; Pinto, Francisco María; Báez, Delia; Bello, Aixa R; Candenas, Luz; Almeida, Teresa A","year":2016,"journal":"Fertility and sterility, 106(6), 1521-1529","doi":"10.1016/j.fertnstert.2016.07.007","pmid":"27456549","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The study demonstrated a significant up-regulation of TAC1 mRNA and increased protein expression of the truncated neurokinin 1 receptor isoform (NK1R-Tr) in uterine leiomyomas compared to adjacent normal myometrium. TACR2 mRNA was also elevated, although NK2R protein levels remained unchanged. These alterations suggest differential regulation of the entire tachykinin system in leiomyomas.","whyItMatters":"Understanding the altered expression of tachykinins and their receptors in fibroids could reveal new molecular targets for treatment. Since these peptides may promote tumor growth, targeting their signaling pathways might help manage or reduce fibroid size.","specificNumbers":"","methodology":"The researchers collected paired samples of uterine leiomyomas and adjacent normal myometrium from women undergoing hysterectomy. They used quantitative polymerase chain reaction (qPCR), immunohistochemistry, and Western blotting to measure mRNA and protein levels of tachykinins and their receptors.","limitations":"The study was conducted on tissue samples from a limited number of patients, and the functional effects of the altered tachykinin expression were not directly tested. The evidence strength and study type were not clearly defined."},{"rthcId":"RPEP-02946","title":"High-molecular-weight poly(Gly-Val-Gly-Val-Pro) synthesis through microwave irradiation.","authors":"Goto, Mitsuaki; Endo, Takeshi","year":2016,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 22(7), 452-60","doi":"10.1002/psc.2866","pmid":"27352997","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Microwave irradiation in the presence of optimized additives and solvents facilitates the polycondensation of the pentapeptide GVGVP into high-molecular-weight poly(GVGVP) with molecular weights exceeding 7000 Da, achieving gram-scale synthesis with temperature-sensitive properties comparable to recombinant polypeptides.","whyItMatters":"This method provides a faster, scalable alternative to genetic engineering for producing elastin-like polypeptides, which are important for biomaterials and peptide research due to their unique temperature-responsive properties.","specificNumbers":"","methodology":"The study used microwave irradiation to induce polycondensation of the elastin pentapeptide GVGVP in the presence of various additives, coupling agents, and solvents. Reaction conditions were optimized to maximize yield and molecular weight, and the product was characterized for molecular weight and temperature sensitivity.","limitations":"The study does not specify the detailed reaction yields or compare mechanical properties of the synthesized polypeptides to natural elastin. The evidence strength and study type are not clearly defined."},{"rthcId":"RPEP-02947","title":"GLP-1 Agonists and Blood Pressure: A Review of the Evidence.","authors":"Goud, Aditya; Zhong, Jixin; Peters, Matthew; Brook, Robert D; Rajagopalan, Sanjay","year":2016,"journal":"Current hypertension reports, 18(2), 16","doi":"10.1007/s11906-015-0621-6","pmid":"26803771","tags":["glp-1-agonists"],"studyType":"Review","evidenceStrength":"moderate","keyFinding":"GLP-1 receptor agonists appear to modestly lower systolic blood pressure by approximately 2 mmHg with chronic use, but the effect is inconsistent. A single dose can actually increase blood pressure acutely. Two controlled clinical trials that measured ambulatory blood pressure as the primary endpoint did not consistently confirm the blood pressure–lowering effect.\n\nGLP-1 drugs also increase heart rate. The blood pressure reduction observed in diabetes trials may partly reflect weight loss rather than a direct drug effect. Animal studies suggest the drugs could act through vascular, kidney, heart, and brain pathways, but these mechanisms haven't been confirmed in humans.","whyItMatters":"Millions of people taking GLP-1 drugs for diabetes or obesity also have high blood pressure. Whether these drugs help or hurt blood pressure matters enormously for cardiovascular outcomes. The modest systolic reduction (~2 mmHg), if real, could contribute to the cardiovascular benefits seen in large outcome trials like LEADER and SUSTAIN-6. But the simultaneous heart rate increase complicates the picture.","specificNumbers":"~2 mmHg systolic BP reduction with chronic use · heart rate increase observed · 2 RCTs with ambulatory BP as primary endpoint showed inconsistent results","methodology":"Narrative review of preclinical (mouse models) and clinical evidence on GLP-1 receptor agonists and blood pressure. The authors examined acute vs. chronic dosing effects, clinic vs. ambulatory blood pressure measurements, proposed mechanisms (vascular, renal, cardiac, CNS), and data from glycemia-lowering trials where blood pressure was a secondary endpoint.","limitations":"Most blood pressure data comes from diabetes trials where BP was a secondary endpoint — not the primary focus. When BP was the primary endpoint in controlled trials, results were inconsistent. The review cannot distinguish whether BP effects are direct drug actions or indirect effects of weight loss. Animal mechanism studies may not translate to humans. Published in 2016 before major cardiovascular outcome trials were completed."},{"rthcId":"RPEP-02948","title":"The cytoskeleton as a drug target for neuroprotection: the case of the autism- mutated ADNP.","authors":"Gozes, Illana","year":2016,"journal":"Biological chemistry, 397(3), 177-84","doi":"10.1515/hsz-2015-0152","pmid":"25955282","tags":["neuroprotection","nap-peptide","neurodevelopment"],"studyType":"Review / Perspective","evidenceStrength":"Review/Reference","keyFinding":"Activity-dependent neuroprotective protein (ADNP) is essential for brain formation and function, and mutations in the ADNP gene are a leading cause of autism. The ADNP protein interacts with the cell's cytoskeleton through microtubule end-binding (EB) proteins and with the autophagy regulator LC3.\n\nCritically, the peptide drug candidate NAP (davunetide, sequence NAPVSIPQ) — derived from ADNP — shares the same SIP domain that mediates ADNP's binding to EB proteins. This identifies a precise molecular target for NAP/davunetide's neuroprotective effects: it protects brain cells by stabilizing the cytoskeleton through the same binding site that ADNP naturally uses. ADNP was also found to be part of the SWI/SNF chromatin remodeling complex, linking it to tau splicing and tauopathy prediction.","whyItMatters":"This paper connects several major threads in neuroscience: autism genetics (ADNP mutations), neurodegeneration (tau pathology and Alzheimer's), and peptide drug development (davunetide). By identifying the precise molecular target of NAP/davunetide — the EB-binding SIP domain on the cytoskeleton — it moves the field from knowing the peptide works to understanding exactly how it works. This mechanistic clarity is essential for improving peptide drug design and for understanding why ADNP mutations cause neurodevelopmental disorders.","specificNumbers":"15 years of ADNP research · NAPVSIPQ (8 amino acid peptide) · SIP domain binding to EB proteins · LC3 autophagy regulator interaction · SWI/SNF chromatin complex","methodology":"This is a perspective/review article summarizing 15 years of the author's research program on ADNP and its peptide fragment NAP (davunetide). It integrates findings from protein interaction studies, cytoskeletal binding assays, and chromatin remodeling research to present a unified model of ADNP/NAP neuroprotection.","limitations":"This is a review from the laboratory that discovered ADNP, which may introduce perspective bias. The precise molecular target identification is based on in vitro protein interaction data and may not fully capture the complexity of NAP's effects in living brain tissue. Davunetide's clinical trial for progressive supranuclear palsy (a tauopathy) failed to meet its primary endpoints, raising questions about translating these mechanistic findings to clinical benefit."},{"rthcId":"RPEP-02949","title":"Peripheral activities of growth hormone-releasing hormone.","authors":"Granata, R","year":2016,"journal":"Journal of endocrinological investigation, 39(7), 721-7","doi":"10.1007/s40618-016-0440-x","pmid":"26891937","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GHRH and its receptors are expressed in multiple peripheral tissues where GHRH regulates cell proliferation, survival, differentiation, and apoptosis inhibition. It influences pancreatic β-cell function, endometrial proliferation, cardioprotection, wound healing, immune modulation, inflammation reduction, lifespan extension, adiposity, and skeletal muscle cell survival.","whyItMatters":"Understanding GHRH's peripheral actions opens new avenues for therapeutic applications of GHRH analogs in conditions like diabetes, cardiovascular disease, immune disorders, and muscle wasting.","specificNumbers":"","methodology":"This article reviews existing research on the peripheral roles of GHRH, summarizing findings on its expression and effects in various tissues outside the pituitary gland.","limitations":"The study is a review and does not provide new experimental data; the strength of evidence for some peripheral effects varies and requires further validation."},{"rthcId":"RPEP-02950","title":"Bioactivity of a Rice Bran-Derived Peptide and its Sensory Evaluation and Storage Stability in Orange Juice.","authors":"Graves, Amanda M; Hettiarachchy, Navam; Rayaprolu, Srinivas; Li, Ruiqi; Horax, Ronny; Seo, Han-Seok","year":2016,"journal":"Journal of food science, 81(4), H1010-5","doi":"10.1111/1750-3841.13245","pmid":"26894442","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The rice bran-derived pentapeptide inhibited human prostate cancer cell growth by 45% at 460 μg/mL. When incorporated into spray-dried orange juice, the peptide showed approximately 10% degradation at 620 μg/mL under refrigerated storage over six months, with higher degradation at ambient temperature and lower concentrations. Sensory evaluation indicated good acceptability except for a slight bitterness.","whyItMatters":"This study demonstrates the potential of rice bran peptides as functional food ingredients with anticancer properties. Understanding peptide stability and sensory impact in food products is crucial for developing effective health-promoting beverages.","specificNumbers":"","methodology":"The study evaluated the inhibitory effect of a rice bran pentapeptide on human prostate cancer cells in vitro. The peptide was incorporated into spray-dried orange juice, which was stored for six months under refrigerated and ambient conditions to assess peptide stability. Sensory evaluation was conducted with consumer panelists to assess acceptability of the reconstituted beverage.","limitations":"The study did not specify the sample size or detailed sensory panel demographics, and the in vitro results may not directly translate to effects in humans. The bitterness of the peptide may limit consumer acceptance without further formulation improvements."},{"rthcId":"RPEP-02951","title":"Influence of Clinical Trial Site Enrollment on Patient Characteristics, Protocol Completion, and End Points: Insights From the ASCEND-HF Trial (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure).","authors":"Greene, Stephen J; Hernandez, Adrian F; Sun, Jie-Lena; Metra, Marco; Butler, Javed; Ambrosy, Andrew P; Ezekowitz, Justin A; Starling, Randall C; Teerlink, John R; Schulte, Phillip J; Voors, Adriaan A; Armstrong, Paul W; O'Connor, Christopher M; Mentz, Robert J","year":2016,"journal":"Circulation. Heart failure, 9(9)","doi":"10.1161/CIRCHEARTFAILURE.116.002986","pmid":"27623769","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02952","title":"Stable gastric pentadecapeptide BPC 157 heals rat colovesical fistula.","authors":"Grgic, Tihomir; Grgic, Dora; Drmic, Domagoj; Sever, Anita Zenko; Petrovic, Igor; Sucic, Mario; Kokot, Antonio; Klicek, Robert; Sever, Marko; Seiwerth, Sven; Sikiric, Predrag","year":2016,"journal":"European journal of pharmacology, 780, 1-7","doi":"10.1016/j.ejphar.2016.02.038","pmid":"26875638","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BPC 157 administered orally or intraperitoneally at doses of 10 µg/kg or 10 ng/kg significantly accelerated healing of colovesical fistulas in rats. Treated rats showed closure of colon and bladder defects, elimination of fistula leakage, and prevention of adhesions and intestinal obstruction.","whyItMatters":"This study suggests BPC 157 could be a promising therapeutic peptide for treating difficult-to-heal fistulas, which are a serious complication in gastrointestinal diseases. Effective healing of fistulas can improve patient outcomes and reduce the need for invasive surgeries.","specificNumbers":"","methodology":"Male Wistar Albino rats with surgically induced colovesical fistulas were randomly assigned to receive BPC 157 orally in drinking water or via intraperitoneal injection at specified doses. Controls received saline or water. Healing was assessed at 7, 14, and 28 days by examining fistula closure, leakage, fecaluria, adhesions, and intestinal obstruction.","limitations":"The study was conducted in rats, so results may not fully translate to humans. The exact mechanisms of BPC 157’s healing effects were not explored in detail. The study type and evidence strength were not specified."},{"rthcId":"RPEP-02953","title":"Postprandial effects of consuming a staggered meal on gut peptide and glycemic responses in obese women and men.","authors":"Griffith, Lisa; Haddad, Ella H; Tonstad, Serena","year":2016,"journal":"Obesity research & clinical practice, 10(3), 264-74","doi":"10.1016/j.orcp.2015.08.001","pmid":"26311660","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Consuming 86g of beans 15 minutes before the rest of a meal decreased GLP-1 hormone response by 19% and increased glucose levels by 7%, but did not affect other gut peptides, insulin, hunger, fullness, or subsequent energy intake in obese adults.","whyItMatters":"Understanding how meal timing affects gut hormones and appetite can inform dietary strategies for obesity management. This study shows that simply staggering meal consumption may not improve hormonal or appetite control in obese individuals.","specificNumbers":"","methodology":"A randomized crossover study with 28 obese adults compared a control meal containing beans to a staggered meal where beans were eaten 15 minutes prior. Blood samples were taken before and up to 120 minutes after meals to measure gut peptides, glucose, and insulin. Hunger and fullness were assessed by visual scales, and energy intake was recorded via dietary recalls.","limitations":"The study had a relatively small sample size and only tested one type of food and timing interval. The short-term design may not capture long-term effects of staggered eating on metabolism or weight."},{"rthcId":"RPEP-02954","title":"Tumour Risk with Once-Weekly Glucagon-Like Peptide-1 Receptor Agonists in Type 2 Diabetes Mellitus Patients: A Systematic Review.","authors":"Guo, Xia; Yang, Qing; Dong, Jianjun; Liao, Lin; Zhang, Weiwei; Liu, Fupeng","year":2016,"journal":"Clinical drug investigation, 36(6), 433-41","doi":"10.1007/s40261-016-0389-8","pmid":"26979594","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Once-weekly GLP-1 receptor agonists did not increase the risk of tumors compared with other antidiabetic drugs, with a pooled risk ratio of 1.02 (95% CI: 0.74-1.41; p = 0.91). This lack of increased tumor risk was consistent regardless of the specific GLP-1RA used or treatment duration of at least 52 weeks.","whyItMatters":"Understanding the safety of GLP-1 receptor agonists is crucial as they are widely used for type 2 diabetes management. Confirming no increased tumor risk supports their continued use and informs patient and clinician decisions.","specificNumbers":"","methodology":"A systematic review and meta-analysis of 26 randomized controlled trials from ClinicalTrials.gov was conducted, including 16,090 patients. Tumor incidence data were extracted and pooled using the Mantel-Haenszel method and a fixed-effects model to calculate risk ratios.","limitations":"The analysis was limited by the relatively short duration of included trials (minimum one year) and the sample sizes may not detect rare tumor events. Longer-term studies with larger populations are needed to confirm these findings."},{"rthcId":"RPEP-02955","title":"The value of short- and long-acting glucagon-like peptide-1 agonists in the management of type 2 diabetes mellitus: experience with exenatide.","authors":"Guo, Xiao-Hui","year":2016,"journal":"Current medical research and opinion, 32(1), 61-76","doi":"10.1185/03007995.2015.1103214","pmid":"26439329","tags":[],"studyType":"review","evidenceStrength":"review","keyFinding":"Short-acting and long-acting GLP-1 receptor agonists work through different primary mechanisms despite sharing the same target. Short-acting agents (like twice-daily exenatide) primarily reduce postprandial glucose spikes by slowing gastric emptying, while long-acting agents (like once-weekly exenatide) mainly lower fasting blood glucose by sustained stimulation of pancreatic insulin secretion.\n\nOnly about half of type 2 diabetes patients on standard drugs achieve adequate glycemic control (HbA1c <7%), largely due to poor adherence. Exenatide as add-on therapy showed consistent benefits across a large evidence base, with good tolerability and no new safety signals during up to 5 years of follow-up. The clinical differences between formulations allow individualized treatment based on whether a patient's main problem is postmeal spikes or high fasting glucose.","whyItMatters":"The distinction between short- and long-acting GLP-1 agonists is clinically important because it enables personalized diabetes treatment. A patient whose blood sugar spikes mainly after meals benefits more from a short-acting agent, while someone with chronically elevated fasting glucose does better with a long-acting version. This pharmacological insight — that the same molecule can produce different clinical profiles depending on its duration — has shaped how GLP-1 drugs are prescribed.","specificNumbers":"~50% of T2D patients don't reach HbA1c <7% on standard drugs · Up to 5 years of safety data for exenatide · Short-acting: primarily reduces postprandial glucose · Long-acting: primarily reduces fasting glucose · Low hypoglycemia risk","methodology":"PubMed literature search through May 2015 using GLP-1 related keywords, with additional searches for specific drugs (albiglutide, dulaglutide, liraglutide, lixisenatide). Focus on exenatide to avoid confounding from molecular structure differences between agents.","limitations":"Focuses primarily on exenatide rather than the full GLP-1 agonist class, limiting generalizability. Published in 2016, it predates semaglutide and tirzepatide, which have significantly changed the landscape. The single-author review may lack the breadth of a systematic review or meta-analysis."},{"rthcId":"RPEP-02956","title":"Self-assembled peptide-based nanostructures: Smart nanomaterials toward targeted drug delivery.","authors":"Habibi, Neda; Kamaly, Nazila; Memic, Adnan; Shafiee, Hadi","year":2016,"journal":"Nano today, 11(1), 41-60","doi":null,"pmid":"27103939","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Self-assembled peptide nanostructures offer several key advantages as drug delivery vehicles: chemical diversity that allows customization, biocompatibility with human tissue, high loading capacity for both hydrophobic and hydrophilic drugs, and the ability to target specific molecular recognition sites on cells.\n\nBy incorporating novel peptide motifs, researchers can make these structures stimuli-responsive — meaning they remain stable during transport through the body but release their drug cargo when they encounter specific conditions (like the acidic environment of a tumor or certain enzymes at an infection site).","whyItMatters":"Getting drugs to the right place in the body at the right time remains one of medicine's biggest challenges. Self-assembled peptide nanostructures represent a promising solution because they're made from natural amino acid building blocks (so the body tolerates them well), can be designed to seek out disease targets, and can be triggered to release drugs only where needed — potentially reducing side effects while improving treatment effectiveness.","specificNumbers":"","methodology":"This is a comprehensive review article that surveyed recent published studies on self-assembled peptide nanostructures, focusing specifically on their design for targeted and stimuli-responsive drug delivery applications.","limitations":"As a review article, this work summarizes existing research rather than presenting new experimental data. The review was published in 2016, so it does not cover developments from the past decade. Most studies reviewed were preclinical, and clinical translation of self-assembled peptide delivery systems remains limited."},{"rthcId":"RPEP-02957","title":"Capsaicin-Sensitive Sensory Nerves Mediate the Cellular and Microvascular Effects of H2S via TRPA1 Receptor Activation and Neuropeptide Release.","authors":"Hajna, Zsófia; Sághy, Éva; Payrits, Maja; Aubdool, Aisah A; Szőke, Éva; Pozsgai, Gábor; Bátai, István Z; Nagy, Lívia; Filotás, Dániel; Helyes, Zsuzsanna; Brain, Susan D; Pintér, Erika","year":2016,"journal":"Journal of molecular neuroscience : MN, 60(2), 157-70","doi":"10.1007/s12031-016-0802-z","pmid":"27525636","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"H2S activates TRPA1 receptors on capsaicin-sensitive sensory neurons, leading to increased intracellular calcium and vasodilation mediated by the release of neuropeptides CGRP and substance P. This vasodilatory effect is significantly reduced in mice lacking TRPA1 receptors or neuropeptides and after sensory nerve desensitization.","whyItMatters":"Understanding how H2S induces vasodilation via sensory nerves and TRPA1 receptors can help develop new treatments targeting vascular and inflammatory diseases where blood flow regulation is disrupted.","specificNumbers":"","methodology":"The study used calcium imaging on trigeminal ganglia neurons from wild-type and TRPA1 knockout mice to measure intracellular calcium changes after H2S donor application. Cutaneous blood flow changes were assessed by laser Doppler imaging in mouse ears following topical H2S application, with pharmacological blockade and genetic knockout models used to dissect receptor and neuropeptide involvement.","limitations":"The study was conducted in mice and in vitro neuron cultures, so results may not fully translate to humans. The exact molecular mechanisms downstream of TRPA1 activation were not fully explored."},{"rthcId":"RPEP-02958","title":"A novel dual-glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide receptor agonist is neuroprotective in transient focal cerebral ischemia in the rat.","authors":"Han, Ling; Hölscher, Christian; Xue, Guo-Fang; Li, Guanglai; Li, Dongfang","year":2016,"journal":"Neuroreport, 27(1), 23-32","doi":"10.1097/WNR.0000000000000490","pmid":"26555034","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The novel dual GLP-1/GIP receptor agonist significantly reduced neurological deficits, infarct volume, apoptotic neuron percentage, and inflammation markers compared to a GLP-1 receptor agonist alone, indicating superior neuroprotection in a rat model of transient focal cerebral ischemia.","whyItMatters":"This study highlights a promising new therapeutic approach that targets two receptors simultaneously to better protect brain tissue after stroke, which could lead to improved treatments for stroke and neurodegenerative diseases.","specificNumbers":"","methodology":"Rats underwent middle cerebral artery occlusion to simulate stroke and were treated with either the dual GLP-1/GIP receptor agonist or a GLP-1 analog. Neurological function, brain infarct size, and markers of apoptosis and inflammation were assessed at multiple time points post-ischemia.","limitations":"The study was conducted in rats, so results may not directly translate to humans. The exact dosing and long-term effects were not fully explored."},{"rthcId":"RPEP-02959","title":"Hypothalamic regulation of body growth and appetite by ghrelin-derived peptides during balanced nutrition or undernutrition.","authors":"Hassouna, Rim; Labarthe, Alexandra; Tolle, Virginie","year":2016,"journal":"Molecular and cellular endocrinology, 438, 42-51","doi":"10.1016/j.mce.2016.09.027","pmid":"27693419","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Ghrelin and its derived peptides, such as desacyl ghrelin and obestatin, interact within the hypothalamus to regulate body growth, appetite, and energy metabolism. These peptides may act as functional antagonists to ghrelin, modulating the GHS-R receptor and influencing physiological responses differently during balanced nutrition versus chronic undernutrition.","whyItMatters":"Understanding how ghrelin peptides regulate growth and appetite can inform new therapeutic approaches for metabolic disorders, eating disorders, and growth deficiencies.","specificNumbers":"","methodology":"This is a review article summarizing recent pharmacological and genetic studies on the ghrelin/GHS-R system and its role in energy homeostasis and growth regulation under various nutritional conditions.","limitations":"As a review, the study depends on existing research, which may have varying methodologies and evidence strengths; direct experimental data on some mechanisms remain limited."},{"rthcId":"RPEP-02960","title":"Binding Selectivity of Abaloparatide for PTH-Type-1-Receptor Conformations and Effects on Downstream Signaling.","authors":"Hattersley, Gary; Dean, Thomas; Corbin, Braden A; Bahar, Hila; Gardella, Thomas J","year":2016,"journal":"Endocrinology, 157(1), 141-9","doi":"10.1210/en.2015-1726","pmid":"26562265","tags":["osteoporosis","bone-health","pth-analogs"],"studyType":"In Vitro / Mechanistic","evidenceStrength":"Preliminary","keyFinding":"Abaloparatide (a synthetic analog of PTHrP) binds more selectively to the RG conformation of the PTH type 1 receptor (PTHR1) compared to the R0 conformation, while PTH(1-34) (teriparatide) binds both conformations more equally.\n\nThis RG-selective binding produces more transient cAMP signaling responses in PTHR1-expressing cells. Because transient (intermittent-like) receptor activation favors bone formation over bone resorption, this receptor selectivity provides a molecular explanation for why abaloparatide may build bone with less accompanying bone loss and fewer hypercalcemic side effects than teriparatide.","whyItMatters":"Osteoporosis treatments that stimulate bone formation are powerful but come with trade-offs — teriparatide (PTH 1-34) can also increase bone resorption and raise calcium levels. This study reveals the molecular reason why abaloparatide may have a better safety profile: it activates the receptor in a more transient way that preferentially drives bone building. Understanding this mechanism helps explain clinical differences between the two drugs and could guide the design of even better bone-building peptides in the future.","specificNumbers":"RG vs R0 conformation selectivity · more transient cAMP responses · in vitro HEK293 cells","methodology":"The researchers used HEK293 cells engineered to express the PTH type 1 receptor (PTHR1) and performed binding assays to measure how abaloparatide and PTH(1-34) interact with two different receptor conformations (R0 and RG). They then measured downstream cAMP signaling responses to determine whether each peptide produced sustained or transient cellular activation.","limitations":"This is an in vitro study using engineered cell lines, not human bone tissue or animal models. The receptor binding and signaling results may not directly translate to the complexity of bone biology in living organisms. The study does not include clinical outcomes or patient data."},{"rthcId":"RPEP-02961","title":"Effects of exercise intensity on plasma concentrations of appetite-regulating hormones: Potential mechanisms.","authors":"Hazell, Tom J; Islam, Hashim; Townsend, Logan K; Schmale, Matt S; Copeland, Jennifer L","year":2016,"journal":"Appetite, 98, 80-8","doi":"10.1016/j.appet.2015.12.016","pmid":"26721721","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Acute exercise leads to intensity-dependent changes in appetite-regulating hormones, with higher intensity exercise causing greater suppression of the orexigenic hormone acylated ghrelin and increased levels of anorexigenic hormones such as peptide YY (PYY), glucagon-like peptide-1 (GLP-1), and pancreatic polypeptide (PP).","whyItMatters":"Understanding how exercise intensity influences appetite hormones can improve weight loss programs by tailoring exercise to better control hunger and satiety signals.","specificNumbers":"","methodology":"This article is a review of existing research studies examining how different intensities of exercise affect circulating concentrations of appetite-regulating hormones and explores potential physiological mechanisms behind these changes.","limitations":"The review notes limited research on how these hormonal responses vary by sex and age, and the evidence strength and study types are not clearly defined."},{"rthcId":"RPEP-02962","title":"Increased peptide YY blood concentrations, not decreased acyl-ghrelin, are associated with reduced hunger and food intake in healthy older women: Preliminary evidence.","authors":"Hickson, Mary; Moss, Charlotte; Dhillo, Waljit S; Bottin, Jeanne; Frost, Gary","year":2016,"journal":"Appetite, 105, 320-7","doi":"10.1016/j.appet.2016.06.002","pmid":"27264721","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Postprandial peptide YY (PYY) levels were significantly higher in older women compared to younger women, correlating with reduced subjective hunger and lower energy intake. No significant differences were observed in ghrelin or acyl-ghrelin concentrations between age groups.","whyItMatters":"Understanding how appetite hormones change with age can help address anorexia of ageing, potentially guiding interventions to improve nutrition and health in older adults.","specificNumbers":"","methodology":"A cross-sectional study involving 31 healthy female volunteers aged 21 to 92 years was conducted. Participants consumed a standardized 660 kcal test meal, after which blood levels of appetite hormones (total ghrelin, acyl-ghrelin, PYY, GLP-1) and subjective appetite ratings were measured and compared across age groups.","limitations":"The study had a small sample size and was cross-sectional, limiting the ability to establish causality. The evidence strength and study type were not clearly defined."},{"rthcId":"RPEP-02963","title":"Systematic Analysis of Intracellular-targeting Antimicrobial Peptides, Bactenecin 7, Hybrid of Pleurocidin and Dermaseptin, Proline-Arginine-rich Peptide, and Lactoferricin B, by Using Escherichia coli Proteome Microarrays.","authors":"Ho, Yu-Hsuan; Shah, Pramod; Chen, Yi-Wen; Chen, Chien-Sheng","year":2016,"journal":"Molecular & cellular proteomics : MCP, 15(6), 1837-47","doi":"10.1074/mcp.M115.054999","pmid":"26902206","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Using E. coli proteome microarrays, the researchers mapped intracellular targets for four AMPs:\n\n- Bactenecin 7 (Bac7): targets purine metabolism and histidine kinase\n- Lactoferricin B (LfcinB): attacks transcription-related activities and carbohydrate biosynthesis\n- Pleurocidin-dermaseptin hybrid (P-Der): affects small molecule catabolic processes\n- Proline-arginine-rich peptide (PR-39): recognizes RNA and folate metabolism proteins\n\nOverlapping targets revealed synergistic potential: Bac7 and LfcinB both target purine metabolism, while LfcinB and PR-39 both target lipopolysaccharide biosynthesis. These predicted synergies were confirmed in antimicrobial assays.\n\nAll four AMPs target arginine decarboxylase, essential for E. coli survival in extremely acidic environments. Correspondingly, all four showed greater bacterial growth inhibition under acidic conditions, confirmed experimentally.","whyItMatters":"Antibiotic resistance is one of the greatest global health threats. Antimicrobial peptides are a promising alternative, but developing them into drugs requires understanding exactly how they kill bacteria. This study provides the first systematic map of intracellular AMP targets, revealing which bacterial processes are vulnerable and how peptides can be combined for enhanced killing power. This rational, target-based approach could accelerate the development of peptide-based antibiotics.","specificNumbers":"","methodology":"The researchers used an E. coli proteome microarray — a chip containing thousands of individual E. coli proteins — to screen for protein interactions with three fluorescently labeled AMPs (Bac7, P-Der, PR-39), incorporating previous data for LfcinB. Protein targets were analyzed using KEGG pathway analysis to identify affected biological processes. Predicted synergistic combinations were validated through antimicrobial assays, and the acidic environment hypothesis was tested with bacterial growth inhibition experiments under different pH conditions.","limitations":"The study used only E. coli and results may not translate to other bacterial species, particularly Gram-positive bacteria which have fundamentally different cell structures. Proteome microarrays measure binding interactions, not necessarily functional inhibition — a peptide binding a protein doesn't guarantee it disrupts that protein's activity. The study was conducted in vitro and does not address how these peptides would perform in an infection model. The concentrations used on the microarray may differ from those achieved at the bacterial intracellular level in a real infection."},{"rthcId":"RPEP-02964","title":"Changes in hunger and fullness in relation to gut peptides before and after 8 weeks of alternate day fasting.","authors":"Hoddy, Kristin K; Gibbons, Catherine; Kroeger, Cynthia M; Trepanowski, John F; Barnosky, Adrienne; Bhutani, Surabhi; Gabel, Kelsey; Finlayson, Graham; Varady, Krista A","year":2016,"journal":"Clinical nutrition (Edinburgh, Scotland), 35(6), 1380-1385","doi":"10.1016/j.clnu.2016.03.011","pmid":"27062219","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"After 8 weeks of alternate day fasting, obese subjects lost an average of 3.9 kg, experienced increased fullness and PYY levels, and did not report increased hunger despite elevated ghrelin levels. Fasting leptin and insulin decreased, and resting metabolic rate declined.","whyItMatters":"Understanding how alternate day fasting influences hunger and fullness hormones helps explain why it can be an effective weight loss strategy without causing increased hunger, which often undermines dieting efforts.","specificNumbers":"","methodology":"Fifty-nine obese participants followed an 8-week alternate day fasting protocol with controlled food intake on fast days. Body composition, metabolic rate, appetite ratings, and gut peptide levels were measured before and after the intervention.","limitations":"The study duration was relatively short at 8 weeks, and the sample size was moderate; longer studies are needed to confirm long-term effects and adherence."},{"rthcId":"RPEP-02965","title":"Bridging computational modeling with amino acid replacements to investigate GHS-R1a-peptidomimetic recognition.","authors":"Hou, Jinqiang; Charron, Carlie L; Fowkes, Milan M; Luyt, Leonard G","year":2016,"journal":"European journal of medicinal chemistry, 123, 822-833","doi":"10.1016/j.ejmech.2016.07.078","pmid":"27541265","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Through computational modeling and amino acid replacement experiments, the study revealed that the first three residues of the peptidomimetic G-7039 bind to three distinct hydrophobic sub-pockets in the ghrelin receptor (GHS-R1a). Contrary to previous reports suggesting that a charge-charge interaction between the agonist's terminal amine and Glu124 serves as the primary anchor point, this study demonstrated that this electrostatic interaction alone is insufficient to anchor the ligand — hydrophobic interactions are the dominant binding force.","whyItMatters":"The ghrelin receptor is a therapeutic target for conditions ranging from obesity to growth disorders. Getting the binding mechanism right is essential for designing effective drugs. This study corrects a previous assumption about how ligands bind, which could redirect drug design efforts toward optimizing hydrophobic contacts rather than charge-based interactions.","specificNumbers":"","methodology":"The researchers combined multiple computational approaches: homology modeling to build a structural model of the ghrelin receptor, molecular docking to predict how G-7039 fits into the receptor, molecular dynamics simulations to observe binding behavior over time, and binding free energy calculations to quantify interaction strength. They also made systematic amino acid replacements on G-7039 to test which parts of the molecule are most important for binding.","limitations":"This study relies entirely on computational models and simulations without direct experimental validation of the predicted binding interactions (such as X-ray crystallography or cryo-EM). The homology model of the receptor introduces uncertainty, as the ghrelin receptor's crystal structure was not available at the time. The findings apply specifically to G-7039 and may not generalize to all ghrelin receptor ligands."},{"rthcId":"RPEP-02966","title":"Mitochondria-targeted peptide SS-31 attenuates renal injury via an antioxidant effect in diabetic nephropathy.","authors":"Hou, Yanjuan; Li, Shuangcheng; Wu, Ming; Wei, Jinying; Ren, Yunzhuo; Du, Chunyang; Wu, Haijiang; Han, Caili; Duan, Huijun; Shi, Yonghong","year":2016,"journal":"American journal of physiology. Renal physiology, 310(6), F547-59","doi":"10.1152/ajprenal.00574.2014","pmid":"26719366","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"SS-31 treatment in diabetic mice significantly reduced proteinuria, oxidative DNA damage, renal fibrosis markers, and apoptosis in kidney cells. It inhibited key oxidative stress pathways including NADPH oxidase activity and restored mitochondrial function in mouse mesangial cells exposed to high glucose.","whyItMatters":"This research highlights SS-31 as a promising mitochondria-targeted antioxidant peptide that can protect against diabetic kidney injury, a major complication of diabetes. Understanding its mechanism may guide development of new therapies to prevent or treat diabetic nephropathy.","specificNumbers":"","methodology":"The study used diabetic CD-1 mice subjected to uninephrectomy and streptozotocin to induce diabetic nephropathy, followed by daily intraperitoneal injections of SS-31 for 8 weeks. In vitro experiments were conducted on mouse mesangial cells exposed to high-glucose conditions to assess SS-31's effects on oxidative stress and apoptosis.","limitations":"The study was conducted in a mouse model and cultured cells, so results may not fully translate to humans. The exact clinical efficacy and safety of SS-31 in diabetic patients remain to be established."},{"rthcId":"RPEP-02967","title":"Ginkgoghrelins, unique acylated flavonoid diglycosides in Folium Ginkgo, stimulate growth hormone secretion via activation of the ghrelin receptor.","authors":"Hsieh, Sheng-Kuo; Chung, Tse-Yu; Li, Yue-Chiun; Lo, Yuan-Hao; Lin, Nan-Hei; Kuo, Ping-Chung; Chen, Wen-Ying; Tzen, Jason T C","year":2016,"journal":"Journal of ethnopharmacology, 193, 237-247","doi":"10.1016/j.jep.2016.08.015","pmid":"27523747","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Ginkgoghrelins, acylated flavonoid diglycosides isolated from Folium Ginkgo, stimulate growth hormone secretion in rat anterior pituitary cells via activation of the ghrelin receptor. Their effect is dose-dependent and can be inhibited by a ghrelin receptor inverse agonist. Molecular docking supports their interaction within the ghrelin receptor binding pocket.","whyItMatters":"Identifying non-peptidyl compounds that activate the ghrelin receptor could lead to new anti-aging therapies and alternatives to peptide-based growth hormone stimulators. This expands potential therapeutic options derived from traditional herbal medicines.","specificNumbers":"","methodology":"The study isolated two candidate compounds from Folium Ginkgo methanol extracts and confirmed their structures spectroscopically. Growth hormone release was measured in rat primary anterior pituitary cells exposed to ginkgoghrelins. Metabolites were analyzed in rat bile after intravenous injection using mass spectrometry. Molecular modeling was performed to explore receptor binding.","limitations":"The study was conducted in vitro using rat cells and intravenous administration in rats, which may not fully represent effects in humans. The evidence strength and clinical relevance remain to be established."},{"rthcId":"RPEP-02968","title":"The Role of Substance P in Pulmonary Clearance of Bacteria in Comparative Injury Models.","authors":"Hsieh, Terry; Vaickus, Max H; Stein, Thor D; Lussier, Bethany L; Kim, Jiyoun; Stepien, David M; Duffy, Elizabeth R; Chiswick, Evan L; Remick, Daniel G","year":2016,"journal":"The American journal of pathology, 186(12), 3236-3245","doi":"10.1016/j.ajpath.2016.08.014","pmid":"27876152","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Mice with mild traumatic brain injury (mTBI) showed increased survival, enhanced pulmonary neutrophil recruitment, improved bacterial clearance, and greater phagocytic killing of bacteria compared to mice with mild tail trauma. Blocking substance P signaling via neurokinin-1 receptor antagonism abolished these immune benefits in mTBI mice.","whyItMatters":"Understanding how substance P enhances immune defense after brain injury could lead to new treatments to boost infection clearance in patients with trauma. It highlights a neuroimmune mechanism that may be targeted to improve outcomes in pneumonia and other infections.","specificNumbers":"","methodology":"The study used murine models of mild traumatic brain injury and mild tail trauma to compare immune responses to pneumonia challenge. Researchers measured survival, neutrophil recruitment, bacterial clearance, and phagocytic activity, and tested the effects of neurokinin-1 receptor antagonists to block substance P signaling.","limitations":"The study was conducted in mice, so results may not fully translate to humans. The exact molecular pathways downstream of substance P were not fully elucidated, and the evidence strength and study type were not specified."},{"rthcId":"RPEP-02969","title":"The effects of a low-carbohydrate diet on appetite: A randomized controlled trial.","authors":"Hu, T; Yao, L; Reynolds, K; Niu, T; Li, S; Whelton, P; He, J; Bazzano, L","year":2016,"journal":"Nutrition, metabolism, and cardiovascular diseases : NMCD, 26(6), 476-88","doi":"10.1016/j.numecd.2015.11.011","pmid":"26803589","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"After 12 months, the low-fat diet group experienced a greater reduction in peptide YY levels (-44.2 pg/mL) compared to the low-carbohydrate group (-34.8 pg/mL), with a statistically significant net difference of 9.54 pg/mL (p = 0.036). No significant differences were observed in ghrelin levels or self-reported appetite changes between groups.","whyItMatters":"Understanding how different diets affect appetite hormones can help optimize weight loss strategies and improve long-term diet adherence by managing hunger and fullness.","specificNumbers":"","methodology":"A randomized controlled trial assigned 148 adults with obesity to either a low-carbohydrate diet (<40 g/day carbs) or a low-fat diet (<30% energy from fat) for 12 months. Appetite-related hormones and self-reported appetite were measured at baseline, 3, 6, and 12 months. Both groups received similar behavioral counseling and maintained baseline physical activity.","limitations":"The study did not find differences in self-reported appetite, which may be influenced by subjective factors. Also, the evidence strength and study type were not specified, limiting assessment of overall reliability."},{"rthcId":"RPEP-02970","title":"Acute food deprivation enhances fear extinction but inhibits long-term depression in the lateral amygdala via ghrelin signaling.","authors":"Huang, Chiung-Chun; Chou, Dylan; Yeh, Che-Ming; Hsu, Kuei-Sen","year":2016,"journal":"Neuropharmacology, 101, 36-45","doi":"10.1016/j.neuropharm.2015.09.018","pmid":"26384653","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Acute food deprivation elevates plasma acylated ghrelin, enhancing fear extinction and retention in mice. However, it impairs induction of paired-pulse low-frequency stimulation (PP-LFS) and group I metabotropic glutamate receptor agonist (DHPG)-induced long-term depression (LTD) at thalamic-lateral amygdala synapses. These effects are mediated via ghrelin signaling through growth hormone secretagogue receptor type-1a.","whyItMatters":"Understanding how hunger-related hormones like ghrelin influence fear memory and brain synaptic plasticity can help develop new treatments for anxiety disorders and PTSD by targeting these pathways.","specificNumbers":"","methodology":"The study used mice subjected to acute food deprivation and measured plasma ghrelin levels, fear extinction behavior, and electrophysiological recordings of synaptic plasticity at thalamic inputs to lateral amygdala neurons. Pharmacological agents were used to block ghrelin receptors and induce LTD via different stimulation protocols.","limitations":"The study was conducted in mice, so results may not fully translate to humans. The exact study type and evidence strength were not specified, limiting assessment of robustness."},{"rthcId":"RPEP-02971","title":"Redox-Dependent Modulation of T-Type Ca(2+) Channels in Sensory Neurons Contributes to Acute Anti-Nociceptive Effect of Substance P.","authors":"Huang, Dongyang; Huang, Sha; Gao, Haixia; Liu, Yani; Qi, Jinlong; Chen, Pingping; Wang, Caixue; Scragg, Jason L; Vakurov, Alexander; Peers, Chris; Du, Xiaona; Zhang, Hailin; Gamper, Nikita","year":2016,"journal":"Antioxidants & redox signaling, 25(5), 233-51","doi":"10.1089/ars.2015.6560","pmid":"27306612","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Substance P acutely inhibits T-type CaV3.2 calcium channels in peripheral nociceptors via NK1 receptor-mediated reactive oxygen species production, which modulates channel sensitivity to ambient zinc. This redox-dependent inhibition contributes to the peripheral anti-nociceptive effect of Substance P in vivo.","whyItMatters":"Understanding how Substance P modulates pain at the peripheral level reveals new targets for pain relief therapies. This redox and zinc-dependent mechanism offers insight into endogenous analgesia and potential peptide-based interventions.","specificNumbers":"","methodology":"The study used electrophysiological recordings of T-type calcium channel activity in sensory neurons, pharmacological manipulations with reducing agents, zinc chelators, and genetic modification of the zinc-binding site in CaV3.2 channels. In vivo rat models assessed the anti-nociceptive effects of peripherally applied Substance P and CaV3.2 knockdown.","limitations":"The exact study type and evidence strength were not specified, limiting assessment of robustness. The findings are primarily from animal models and in vitro experiments, which may not fully translate to humans."},{"rthcId":"RPEP-02972","title":"Selective Covalent Targeting of Anti-Apoptotic BFL-1 by Cysteine-Reactive Stapled Peptide Inhibitors.","authors":"Huhn, Annissa J; Guerra, Rachel M; Harvey, Edward P; Bird, Gregory H; Walensky, Loren D","year":2016,"journal":"Cell chemical biology, 23(9), 1123-1134","doi":"10.1016/j.chembiol.2016.07.022","pmid":"27617850","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Stapled BH3 peptides with cysteine-reactive acrylamide groups were designed to covalently and selectively inhibit the anti-apoptotic protein BFL-1 by targeting unique cysteine residues at its BH3-binding pocket.","whyItMatters":"Targeting BFL-1, an anti-apoptotic protein implicated in various cancers, with covalent stapled peptides offers a novel therapeutic strategy to reactivate cell death and potentially improve cancer treatments.","specificNumbers":"","methodology":"The study used structure-guided design to develop stapled peptides bearing acrylamide warheads that covalently bind to cysteines near the BFL-1 BH3-binding site, enabling irreversible inhibition.","limitations":"The study does not specify in vivo efficacy or toxicity data, and the evidence strength and study type are not clearly defined, limiting immediate clinical translation."},{"rthcId":"RPEP-02973","title":"Oral Administration of Collagen Hydrolysates Improves Glucose Tolerance in Normal Mice Through GLP-1-Dependent and GLP-1-Independent Mechanisms.","authors":"Iba, Yoshinori; Yokoi, Koji; Eitoku, Itsuka; Goto, Masaki; Koizumi, Seiko; Sugihara, Fumihito; Oyama, Hiroshi; Yoshimoto, Tadashi","year":2016,"journal":"Journal of medicinal food, 19(9), 836-43","doi":"10.1089/jmf.2016.3711","pmid":"27540823","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Collagen hydrolysates (broken-down collagen peptides) improved blood sugar control in mice through two distinct mechanisms: they inhibited glucose absorption in the intestine (partially through GLP-1) and they enhanced insulin secretion (independent of GLP-1). The collagen peptides also inhibited DPP-IV enzyme activity and stimulated GLP-1 secretion in lab tests. Blocking the GLP-1 receptor only partially reversed the glucose-lowering effect and actually enhanced the insulin secretion boost, confirming that collagen peptides work through multiple pathways.","whyItMatters":"Collagen supplements are hugely popular for skin and joint health, but this study reveals they may also improve blood sugar control — through the same GLP-1 pathway targeted by blockbuster diabetes drugs like semaglutide. The finding that collagen peptides work through both GLP-1-dependent and GLP-1-independent mechanisms suggests they could complement existing diabetes treatments.","specificNumbers":"","methodology":"Researchers first tested collagen hydrolysates in the lab for DPP-IV inhibition and GLP-1 secretion. They then gave collagen peptides orally to normal C57BL mice and measured blood sugar response using oral and intraperitoneal glucose tolerance tests. To tease apart the mechanisms, they pretreated some mice with exendin 9-39 (a GLP-1 receptor blocker). They also measured insulin secretion when collagen was given 45 minutes before glucose, and tested gastric emptying rates.","limitations":"This study used normal (non-diabetic) mice, so results may differ in diabetic animals or humans. The specific peptide sequences responsible for the effects weren't identified. The collagen hydrolysate is a mixture of many peptides, making it unclear which ones drive each mechanism. No human clinical data was generated."},{"rthcId":"RPEP-02974","title":"Isolation of two insecticidal toxins from venom of the Australian theraphosid spider Coremiocnemis tropix.","authors":"Ikonomopoulou, Maria P; Smith, Jennifer J; Herzig, Volker; Pineda, Sandy S; Dziemborowicz, Sławomir; Er, Sing-Yan; Durek, Thomas; Gilchrist, John; Alewood, Paul F; Nicholson, Graham M; Bosmans, Frank; King, Glenn F","year":2016,"journal":"Toxicon : official journal of the International Society on Toxinology, 123, 62-70","doi":"10.1016/j.toxicon.2016.10.013","pmid":"27793656","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Two insecticidal peptides, Ct1a and Ct1b, were isolated from Coremiocnemis tropix venom and found to be lethal to Lucilia cuprina blowflies within 24 hours, with synthetic Ct1a showing an LD50 of 1687 pmol/g. These peptides contain 38-39 amino acids and three disulfide bonds and do not affect voltage-gated sodium channels in other cockroach species.","whyItMatters":"These peptides offer a potential new approach to controlling sheep blowflies, which cause significant economic losses in livestock. Understanding spider venom toxins expands options for developing bioinsecticides that may be more specific and environmentally friendly.","specificNumbers":"","methodology":"Venom fractions from the spider Coremiocnemis tropix were screened for activity against sheep blowflies. Peptides were isolated and their sequences determined by Edman degradation and venom-gland transcriptome sequencing. Synthetic Ct1a was produced via solid-phase peptide synthesis and tested for toxicity and ion channel effects.","limitations":"The study did not determine the precise mechanism of action of the peptides or test their effects on a wide range of non-target species. The low yield of recombinant peptide production may limit scalability."},{"rthcId":"RPEP-02975","title":"Ingestion of bioactive collagen hydrolysates enhance facial skin moisture and elasticity and reduce facial ageing signs in a randomised double-blind placebo-controlled clinical study.","authors":"Inoue, Naoki; Sugihara, Fumihito; Wang, Xuemin","year":2016,"journal":"Journal of the science of food and agriculture, 96(12), 4077-81","doi":"10.1002/jsfa.7606","pmid":"26840887","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The high-content collagen peptide supplement (H-CP) significantly improved all four measured skin parameters compared to placebo at 8 weeks: facial skin moisture, elasticity (R2 measurement), wrinkle depth, and skin roughness. It also outperformed the low-content collagen peptide supplement (L-CP), establishing a dose-response relationship based on Pro-Hyp and Hyp-Gly content.\n\nThe mechanism is supported by prior evidence showing that Pro-Hyp and Hyp-Gly appear in peripheral blood after collagen ingestion, attract dermal fibroblasts (the cells that maintain skin structure), enhance their proliferation, and stimulate hyaluronic acid production — a key molecule for skin hydration. Safety evaluation via blood tests showed no adverse events during the trial.","whyItMatters":"The collagen supplement market is enormous but often criticized for lacking rigorous clinical evidence. This study stands out because it used a proper double-blind placebo-controlled design and demonstrated that not all collagen supplements are equal — the concentration of specific bioactive peptides (Pro-Hyp and Hyp-Gly) matters. This provides consumers and clinicians with a more scientific basis for evaluating collagen products and suggests that peptide composition, not just total collagen content, determines effectiveness.","specificNumbers":"","methodology":"This was a randomized, double-blind, placebo-controlled clinical trial with three groups: high-content collagen peptides (H-CP), low-content collagen peptides (L-CP), and placebo. Skin parameters (moisture, elasticity, wrinkles, roughness) were measured at baseline, 4 weeks, and 8 weeks. Safety was assessed through blood tests. Both collagen products were hydrolysates differing in their concentrations of the bioactive dipeptides Pro-Hyp and Hyp-Gly.","limitations":"The sample size was not specified in the abstract, making it difficult to assess statistical power. The 8-week duration, while sufficient to show effects, does not reveal whether benefits persist with longer use or fade after discontinuation. The study was published by authors potentially affiliated with collagen supplement manufacturers, so conflicts of interest should be considered. Skin measurements were objective but the abstract does not detail the magnitude of improvements. Only facial skin was assessed."},{"rthcId":"RPEP-02976","title":"A Review of Stapled Peptides and Small Molecules to Inhibit Protein-Protein Interactions in Cancer.","authors":"Iyer, Vidhya V","year":2016,"journal":"Current medicinal chemistry, 23(27), 3025-3043","doi":null,"pmid":"27356541","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Stapled peptides and small-molecule inhibitors effectively target protein-protein interactions in key cancer-related proteins such as β-catenin, Bcl-2 family members, and Mdm2. These inhibitors provide a promising strategy to overcome resistance and improve selectivity in cancer therapy.","whyItMatters":"Targeting protein-protein interactions with stapled peptides could overcome limitations of traditional drugs and address previously 'undruggable' cancer targets, potentially improving treatment outcomes.","specificNumbers":"","methodology":"This is a literature review summarizing studies on stapled peptides and small molecules that inhibit protein-protein interactions in mammalian cancer targets. It surveys various protein targets and the development of inhibitors designed to disrupt their interactions.","limitations":"As a review, it does not present new experimental data and the evidence strength and study types of included research vary. The clinical efficacy and safety of stapled peptides remain to be fully established."},{"rthcId":"RPEP-02977","title":"Adherence to NICE guidance on glucagon-like peptide-1 receptor agonists among patients with type 2 diabetes mellitus: an evaluation using the Clinical Practice Research Datalink.","authors":"Jameson, Kevin; D'Oca, Kalpana; Leigh, Paul; Murray-Thomas, Tarita","year":2016,"journal":"Current medical research and opinion, 32(1), 49-60","doi":"10.1185/03007995.2015.1101372","pmid":"26428701","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Only 25% of patients initiated GLP-1 receptor agonists as part of NICE-recommended regimens. Of those on triple therapy, 50% met both HbA1c ≥7.5% and BMI ≥35 kg/m² criteria. At 6 months, 18% on dual therapy and 6.4% on triple therapy achieved target reductions in HbA1c and body weight.","whyItMatters":"Understanding adherence to GLP-1 prescribing guidelines helps identify gaps in diabetes care and informs strategies to improve treatment effectiveness and cost-efficiency.","specificNumbers":"","methodology":"A retrospective cohort study analyzed data from 7,133 primary care patients aged 40 and above who received their first GLP-1 receptor agonist prescription after NICE guideline publication. Patient characteristics and clinical monitoring were assessed using descriptive statistics.","limitations":"Lack of data on patient ethnicity and contraindications limited full assessment of guideline adherence. The retrospective design may miss factors influencing prescribing decisions."},{"rthcId":"RPEP-02978","title":"Efficacy and safety of dulaglutide in the treatment of type 2 diabetes: a comprehensive review of the dulaglutide clinical data focusing on the AWARD phase 3 clinical trial program.","authors":"Jendle, Johan; Grunberger, George; Blevins, Thomas; Giorgino, Francesco; Hietpas, Ryan T; Botros, Fady T","year":2016,"journal":"Diabetes/metabolism research and reviews, 32(8), 776-790","doi":"10.1002/dmrr.2810","pmid":"27102969","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02979","title":"Recombinant expression of porcine lactoferrin peptide LF-6 with intein technology and its immunomodulatory function in ETEC K88-infected mice.","authors":"Jiang, Qin; Zhang, Haiwen; Xie, Yonggang; Wang, Yizhen","year":2016,"journal":"International immunopharmacology, 39, 181-191","doi":"10.1016/j.intimp.2016.07.029","pmid":"27487204","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Recombinant LF-6 produced via intein technology exhibited antibacterial activity comparable to chemically synthesized LF-6 and significantly reduced pro-inflammatory cytokines and intestinal injury in ETEC K88-infected mice, demonstrating both antibacterial and immunomodulatory effects.","whyItMatters":"This work provides a safe and efficient way to produce a highly effective antibacterial peptide with immune benefits, offering potential new treatments against bacterial infections and inflammation-related intestinal damage.","specificNumbers":"","methodology":"The study used an Escherichia coli expression system with intein technology to produce recombinant LF-6 peptide, which was purified and tested for antibacterial activity in vitro. In vivo, the peptide’s immunoprotective effects were evaluated in mice infected with ETEC K88 by measuring cytokine levels and intestinal tissue damage.","limitations":"The study was conducted in mice, so human effects remain unknown. The exact study type and evidence strength were not specified, limiting assessment of clinical relevance."},{"rthcId":"RPEP-02980","title":"Resolvin E1 Inhibits Substance P-Induced Potentiation of TRPV1 in Primary Sensory Neurons.","authors":"Jo, Youn Yi; Lee, Ji Yeon; Park, Chul-Kyu","year":2016,"journal":"Mediators of inflammation, 2016, 5259321","doi":null,"pmid":"27738388","tags":["neuropeptides","pain"],"studyType":"basic-research","evidenceStrength":"preliminary","keyFinding":"Resolvin E1 (RvE1), a molecule derived from omega-3 fatty acids, blocked the ability of substance P — a key pain-signaling neuropeptide — to amplify TRPV1 pain receptor activity in mouse sensory neurons. Even at low concentrations, RvE1 strongly inhibited this pain-sensitizing pathway.\n\nThe mechanism works through a specific receptor called ChemR23 on pain-sensing neurons. When RvE1 activates ChemR23, it triggers a G-protein signaling cascade that counteracts substance P's ability to sensitize TRPV1. Researchers confirmed this by showing that blocking G-protein signaling (with pertussis toxin and GDPβ-S) eliminated RvE1's inhibitory effect. This positions RvE1 as a natural anti-inflammatory pain inhibitor that directly opposes substance P-driven pain sensitization.","whyItMatters":"Substance P is one of the body's primary pain-amplifying peptides, and TRPV1 is the receptor that makes inflamed tissue hypersensitive to heat and touch. This study shows that the body has a built-in counter-system — omega-3-derived resolvins — that can shut down this pain amplification pathway. Understanding this natural off-switch could lead to new pain treatments that work with the body's own resolution mechanisms rather than simply blocking pain signals.","specificNumbers":"Mouse dorsal root ganglion neurons · ChemR23 receptor pathway · Gαi-coupled GPCR mechanism · Low RvE1 concentrations effective · Pertussis toxin and GDPβ-S used as pathway inhibitors","methodology":"Researchers isolated dorsal root ganglion (DRG) neurons from C57BL/6 mice and used patch-clamp electrophysiology to measure TRPV1 channel activity. They applied substance P to sensitize TRPV1, then tested whether Resolvin E1 could block this sensitization. To identify the signaling pathway, they used specific inhibitors: pertussis toxin (blocks Gαi-coupled GPCRs) and GDPβ-S (blocks G-protein signaling). RT-PCR confirmed receptor expression in the neurons.","limitations":"This is an in vitro study using isolated mouse neurons in culture, so results may not directly translate to living animals or humans. No in vivo pain behavior experiments were conducted. The specific concentrations of substance P and RvE1 used in culture may not reflect physiological levels. Mouse DRG neurons may differ from human sensory neurons in receptor expression and signaling."},{"rthcId":"RPEP-02981","title":"The Therapeutic Potential of Targeting Substance P/NK-1R Interactions in Inflammatory CNS Disorders.","authors":"Johnson, M Brittany; Young, Ada D; Marriott, Ian","year":2016,"journal":"Frontiers in cellular neuroscience, 10, 296","doi":"10.3389/fncel.2016.00296","pmid":"28101005","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Substance P and its receptor NK-1R are highly expressed in CNS cells and contribute to the exacerbation of neuroinflammation by activating glial cells. NK-1R antagonists, currently approved for other uses, show potential as adjunct therapies to reduce inflammatory damage in infectious and sterile neurodegenerative CNS disorders.","whyItMatters":"Understanding how substance P/NK-1R interactions worsen brain inflammation opens new avenues for treating neurodegenerative diseases by repurposing existing drugs, potentially improving patient outcomes.","specificNumbers":"","methodology":"This is a review article synthesizing findings from multiple studies on the role of substance P and NK-1R in neuroinflammation and neurodegenerative diseases, discussing molecular expression patterns and therapeutic implications.","limitations":"As a review, the article does not present new experimental data and the therapeutic potential of NK-1R antagonists in CNS disorders requires validation in clinical trials."},{"rthcId":"RPEP-02982","title":"Bacterial strategies of resistance to antimicrobial peptides.","authors":"Joo, Hwang-Soo; Fu, Chih-Iung; Otto, Michael","year":2016,"journal":"Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 371(1695)","doi":"10.1098/rstb.2015.0292","pmid":"27160595","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02983","title":"The Distribution of Substance P and Kisspeptin in the Mediobasal Hypothalamus of the Male Rhesus Monkey and a Comparison of Intravenous Administration of These Peptides to Release GnRH as Reflected by LH Secretion.","authors":"Kalil, Bruna; Ramaswamy, Suresh; Plant, Tony M","year":2016,"journal":"Neuroendocrinology, 103(6), 711-23","doi":"10.1159/000442420","pmid":"26580201","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Substance P fibers closely appose kisspeptin neurons in the arcuate nucleus and median eminence of male rhesus monkeys, but Substance P is not co-expressed in KNDy neurons. Intravenous administration of Substance P failed to induce GnRH release as measured by LH secretion in GnRH-primed, agonadal juvenile monkeys.","whyItMatters":"Understanding how Substance P interacts with kisspeptin neurons helps clarify the regulation of reproductive hormone pulses, which is important for developing treatments for reproductive disorders.","specificNumbers":"","methodology":"The study used immunofluorescence to map Substance P and kisspeptin in the mediobasal hypothalamus of adult male rhesus monkeys. It also tested the effect of intravenous Substance P injections on LH release in GnRH-primed, agonadal juvenile male monkeys.","limitations":"The study was limited by its focus on juvenile agonadal monkeys for hormone release testing and did not assess other routes or doses of Substance P administration. The evidence strength and study type were not clearly defined."},{"rthcId":"RPEP-02984","title":"Glucagon-like peptide-1 receptor agonists in the treatment of type 2 diabetes: Past, present, and future.","authors":"Kalra, Sanjay; Baruah, Manash P; Sahay, Rakesh K; Unnikrishnan, Ambika Gopalakrishnan; Uppal, Shweta; Adetunji, Omolara","year":2016,"journal":"Indian journal of endocrinology and metabolism, 20(2), 254-67","doi":"10.4103/2230-8210.176351","pmid":"27042424","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 receptor agonists improve glycemic control with a low risk of hypoglycemia and provide clinically meaningful weight loss. Multiple agents with varying structures and pharmacokinetics offer tailored treatment options for type 2 diabetes.","whyItMatters":"Understanding the differences among GLP-1 receptor agonists helps clinicians personalize diabetes treatment, improving patient outcomes and minimizing side effects.","specificNumbers":"","methodology":"An extensive literature search was conducted using PubMed with terms related to GLP-1 and its receptor agonists, reviewing clinical trials, pharmacological profiles, safety data, and treatment guidelines.","limitations":"The study is a literature review without new clinical data, and the evidence strength and study types of included articles vary, limiting definitive conclusions."},{"rthcId":"RPEP-02985","title":"Evaluation of Efficacy and Safety of the Glucagon Receptor Antagonist LY2409021 in Patients With Type 2 Diabetes: 12- and 24-Week Phase 2 Studies.","authors":"Kazda, Christof M; Ding, Ying; Kelly, Ronan P; Garhyan, Parag; Shi, Chunxue; Lim, Chay Ngee; Fu, Haoda; Watson, David E; Lewin, Andrew J; Landschulz, William H; Deeg, Mark A; Moller, David E; Hardy, Thomas A","year":2016,"journal":"Diabetes care, 39(7), 1241-9","doi":"10.2337/dc15-1643","pmid":"26681715","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-02986","title":"The key position: influence of staple location on constrained peptide conformation and binding.","authors":"Keeling, Kelly L; Cho, Okki; Scanlon, Denis B; Booker, Grant W; Abell, Andrew D; Wegener, Kate L","year":2016,"journal":"Organic & biomolecular chemistry, 14(41), 9731-9735","doi":null,"pmid":"27722656","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Stapling peptides increased their α-helical content overall, but the specific location of the staple influenced which peptide regions were stabilized. These differences correlated with changes in binding mode and affinity to the talin protein, indicating that staple placement critically affects peptide conformation and interaction.","whyItMatters":"Understanding how staple location affects peptide structure and binding can guide the design of more effective peptide-based probes and therapeutics targeting protein interactions.","specificNumbers":"","methodology":"The study used circular dichroism and NMR spectroscopy to analyze the helical content and structural details of integrin-based peptides with staples placed at different positions. Binding affinity to talin was assessed to correlate structural changes with functional outcomes.","limitations":"The study focused on a single peptide-protein model system, so findings may not generalize across all peptides or targets. The exact study type and evidence strength were not specified."},{"rthcId":"RPEP-02987","title":"Sensitivity of Pseudomonas syringae to Bovine Lactoferrin Hydrolysates and Identification of a Novel Inhibitory Peptide.","authors":"Kim, Woan-Sub; Kim, Pyeung-Hyeun; Shimazaki, Kei-Ichi","year":2016,"journal":"Korean journal for food science of animal resources, 36(4), 487-93","doi":"10.5851/kosfa.2016.36.4.487","pmid":"27621689","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Bovine lactoferrin hydrolysates selectively inhibit Pseudomonas syringae growth in vitro in a dose-dependent manner, while showing no antimicrobial activity against Pseudomonas fluorescens. A novel antimicrobial peptide with the sequence Leu-Arg-Ile-Pro-Ser-Lys-Val-Asp-Ser-Ala was identified from the N-terminus of bLFH.","whyItMatters":"Identifying new antimicrobial peptides from natural sources like bovine lactoferrin could lead to alternative treatments against bacterial pathogens, especially those affecting plants. This expands the potential applications of peptides in agriculture and food safety.","specificNumbers":"","methodology":"The study used chemiluminescence and paper disc plate assays to determine the minimal inhibitory concentration of bovine lactoferrin hydrolysates against Pseudomonas strains in vitro. Peptides with antimicrobial activity were isolated and sequenced using protein sequencing techniques.","limitations":"The study was conducted entirely in vitro, so the effectiveness and safety of the peptides in real-world agricultural settings remain untested. The exact mechanism of antimicrobial action was not explored."},{"rthcId":"RPEP-02988","title":"Variation in the Oxytocin Receptor Gene Predicts Brain Region-Specific Expression and Social Attachment.","authors":"King, Lanikea B; Walum, Hasse; Inoue, Kiyoshi; Eyrich, Nicholas W; Young, Larry J","year":2016,"journal":"Biological psychiatry, 80(2), 160-169","doi":"10.1016/j.biopsych.2015.12.008","pmid":"26893121","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Pyrosequencing revealed allelic imbalance of oxytocin receptor (Oxtr) mRNA, demonstrating that genetic variants directly influence receptor expression — but only in specific brain regions, including the nucleus accumbens, where oxytocin signaling facilitates pair bonding. Next-generation sequencing identified a single polymorphism in an Oxtr intron, near a putative cis-regulatory element, that explained 74% of the variance in striatal Oxtr expression.\n\nThe behavioral consequence was striking: male prairie voles homozygous for the high-expressing allele displayed significantly enhanced social attachment in the partner preference test — the gold-standard behavioral assay for pair bonding in this species. The brain region-specificity of the genetic effect is notable: the same variant influenced expression in the nucleus accumbens but not in other oxytocin receptor-rich brain regions.","whyItMatters":"Intranasal oxytocin is being tested as a treatment for social deficits in autism spectrum disorder, but responses vary widely between individuals. This study reveals that genetic variation in the oxytocin receptor gene could explain why — people with fewer receptors in reward-related brain regions may respond differently to oxytocin therapy. Understanding this genetic basis could eventually enable personalized oxytocin-based treatments, matching therapy to an individual's receptor expression profile.","specificNumbers":"","methodology":"Prairie voles (monogamous rodents with a well-characterized oxytocin system) were studied using multiple complementary approaches. Brain region-specific Oxtr mRNA and oxytocin receptor protein levels were quantified using established neuroanatomic methods (in situ hybridization and receptor autoradiography). Pyrosequencing assessed allelic imbalance in Oxtr mRNA to detect regulatory genetic variants. Next-generation sequencing identified polymorphisms in and near the Oxtr gene. Social attachment was measured using the partner preference test, where voles choose between spending time with their bonded partner or a stranger.","limitations":"This study was conducted in prairie voles, not humans. While prairie voles are the best animal model for social bonding, their oxytocin system differs from humans in important ways. The specific polymorphism identified is vole-specific and may not have a direct human equivalent, though the principle of noncoding regulatory variants influencing OXTR expression likely applies. The sample sizes for behavioral testing are typical for animal neuroscience but would be considered small for human genetic studies. The causal chain from genetic variant to receptor expression to behavior is well-supported but not experimentally proven through gene editing."},{"rthcId":"RPEP-02989","title":"Immune Modulation with Thymosin Alpha 1 Treatment.","authors":"King, R; Tuthill, C","year":2016,"journal":"Vitamins and hormones, 102, 151-78","doi":"10.1016/bs.vh.2016.04.003","pmid":"27450734","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Thymosin alpha 1 acts via Toll-like receptors on myeloid and plasmacytoid dendritic cells, triggering signaling pathways that increase immune-related cytokine production and improve immune cell subsets, indicating its potential to treat immune suppression in various diseases.","whyItMatters":"Understanding how thymosin alpha 1 modulates immune cells can guide development of therapies for immune suppression caused by aging, infections, or cancer, potentially improving patient outcomes.","specificNumbers":"","methodology":"This article summarizes extensive preclinical and clinical studies investigating thymosin alpha 1’s effects on immune cell subsets and immune function across different disease models and conditions.","limitations":"The review does not specify the strength or design details of the included studies, limiting assessment of the robustness of the evidence."},{"rthcId":"RPEP-02990","title":"Protection of neonatal rat cardiac myocytes against radiation-induced damage with agonists of growth hormone-releasing hormone.","authors":"Kiscsatári, Laura; Varga, Zoltán; Schally, Andrew V; Gáspár, Renáta; Nagy, Csilla Terézia; Giricz, Zoltán; Ferdinandy, Péter; Fábián, Gabriella; Kahán, Zsuzsanna; Görbe, Anikó","year":2016,"journal":"Pharmacological research, 111, 859-866","doi":"10.1016/j.phrs.2016.07.036","pmid":"27480202","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GHRH agonists JI-34 and MR-356 significantly improved viability of irradiated neonatal rat cardiac myocytes and reduced radiation-induced reactive oxygen species (ROS) levels. JI-34 showed protective effects at 10 and 100 nM concentrations, while MR-356 was protective at 500 nM. JI-34 also interfered with the activation of SAFE/RISK signaling pathways. Notably, neither compound affected cell viability or proliferation in unirradiated cells, suggesting a radiation-specific protective mechanism.","whyItMatters":"Radiation-induced cardiac damage is a clinically significant but poorly understood side effect of cancer radiotherapy. With limited options to protect the heart during treatment, these GHRH peptide analogs represent a potential new class of cardioprotective agents that could improve quality of life for cancer patients receiving chest radiation.","specificNumbers":"10 Gy radiation dose · JI-34 protective at 10 and 100 nM · MR-356 protective at 500 nM · 52 kDa GHRHR protein isoform detected","methodology":"Cardiac myocytes isolated from newborn rats were cultured and exposed to 10 Gy of radiation. Researchers then tested two synthetic GHRH agonist peptides (JI-34 and MR-356) at various concentrations, measuring cell viability, proliferation, reactive oxygen species levels, signaling pathway activation, and GHRH receptor protein expression via Western blot.","limitations":"This was an in vitro study using neonatal rat heart cells, which may behave differently from adult human cardiac tissue. The radiation-specific protective mechanism needs validation in animal models before any clinical relevance can be assessed. Long-term effects and optimal dosing remain unknown."},{"rthcId":"RPEP-02991","title":"Effects of ghrelin and motilin on smooth muscle contractility of the isolated gastrointestinal tract from the bullfrog and Japanese fire belly newt.","authors":"Kitazawa, Takio; Shimazaki, Misato; Kikuta, Ayumi; Yaosaka, Noriko; Teraoka, Hiroki; Kaiya, Hiroyuki","year":2016,"journal":"General and comparative endocrinology, 232, 51-9","doi":"10.1016/j.ygcen.2015.12.013","pmid":"26704852","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Neither bullfrog ghrelin nor rat ghrelin affected longitudinal smooth muscle contractility of gastrointestinal strips from bullfrogs or Japanese fire belly newts. The ghrelin receptor (GHS-R1a) mRNA was confirmed present in the bullfrog GI tract, with higher expression in intestinal mucosa than gastric mucosa — yet the receptor did not mediate contractile responses.\n\nOther gastrointestinal peptides including substance P, neurotensin, and motilin, plus the muscarinic agonist carbachol, all induced marked contractions, confirming the muscle preparations were functional. This was the first demonstration that motilin induces gastrointestinal contraction in amphibians. The results parallel findings in fish (rainbow trout, goldfish) where ghrelin also lacks gut motility effects, but contrast with mammals and birds where ghrelin is a potent gut motility regulator.","whyItMatters":"Understanding how peptide hormones evolved different functions across species is fundamental to peptide biology. The finding that ghrelin — one of the most studied gut peptides — has completely different gastrointestinal effects in different vertebrate classes cautions against assuming universal peptide function. For drug development, this highlights that peptide receptors being present does not guarantee functional responses, and that animal model selection for peptide drug testing requires careful consideration of species-specific physiology.","specificNumbers":"","methodology":"In vitro smooth muscle contractility experiments using isolated longitudinal gastrointestinal strips from bullfrogs (Rana catesbeiana) and Japanese fire belly newts. Ghrelin (species-matched and rat-derived), motilin, substance P, neurotensin, and carbachol were applied to muscle preparations. GHS-R1a receptor mRNA expression was quantified in bullfrog gastrointestinal tissues.","limitations":"The study used in vitro isolated muscle strips, which may not fully represent in vivo conditions where neural and hormonal factors interact. Only longitudinal muscle contractility was tested; circular muscle responses may differ. The specific sample sizes (number of animals) are not detailed. Only two amphibian species were tested, limiting generalization. The study did not investigate whether ghrelin might affect other GI functions (secretion, blood flow) in amphibians through non-contractile pathways."},{"rthcId":"RPEP-02992","title":"Qualitative identification of growth hormone-releasing hormones in human plasma by means of immunoaffinity purification and LC-HRMS/MS.","authors":"Knoop, Andre; Thomas, Andreas; Fichant, Eric; Delahaut, Philippe; Schänzer, Wilhelm; Thevis, Mario","year":2016,"journal":"Analytical and bioanalytical chemistry, 408(12), 3145-53","doi":"10.1007/s00216-016-9377-3","pmid":"26879649","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"An immunoaffinity purification combined with nano-ultrahigh performance liquid chromatography-high resolution tandem mass spectrometry method was developed and validated to detect four GHRHs and their metabolites in human plasma with high specificity and sensitivity, including detection of a Geref metabolite in a human after subcutaneous injection.","whyItMatters":"This method provides a reliable tool for anti-doping agencies to detect banned GHRHs in athletes' blood, helping enforce fair play in sports. It also advances peptide detection techniques in biological samples.","specificNumbers":"","methodology":"The study used immunoaffinity purification with a polyclonal GHRH antibody and protein A/G monolithic tips to isolate GHRHs from plasma, followed by nano-UHPLC-HRMS/MS for detection. Validation included specificity, linearity, recovery, detection limits, and stability tests. In vivo rat studies and a human volunteer test assessed metabolism and detection windows.","limitations":"The study had limited sample sizes, especially in vivo tests, and noted species differences in metabolism that require further investigation to fully understand detection windows and metabolite profiles."},{"rthcId":"RPEP-02993","title":"Long-acting glucagon-like peptide-1 receptor agonists have direct access to and effects on pro-opiomelanocortin/cocaine- and amphetamine-stimulated transcript neurons in the mouse hypothalamus.","authors":"Knudsen, Lotte Bjerre; Secher, Anna; Hecksher-Sørensen, Jacob; Pyke, Charles","year":2016,"journal":"Journal of diabetes investigation, 7 Suppl 1(Suppl 1), 56-63","doi":"10.1111/jdi.12463","pmid":"27186357","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Long-acting GLP-1 receptor agonists such as liraglutide directly access the arcuate nucleus in the hypothalamus of mice, activating pro-opiomelanocortin (POMC) neurons and increasing cocaine- and amphetamine-regulated transcript (CART) neuropeptide mRNA. This direct neuronal activation correlates with reduced hunger and increased satiety observed clinically.","whyItMatters":"Understanding that GLP-1 receptor agonists directly affect brain neurons controlling appetite provides insight into their weight loss effects, potentially guiding improved obesity treatments.","specificNumbers":"","methodology":"The study used fluorescently labeled liraglutide and other GLP-1 receptor agonists combined with single-plane illumination microscopy to track drug access to mouse brain regions. Molecular analyses measured changes in neuropeptide mRNA levels in specific hypothalamic neurons after drug administration.","limitations":"The study was conducted in mice, so results may not fully translate to humans; the exact clinical relevance and long-term effects require further investigation."},{"rthcId":"RPEP-02994","title":"Hitting a Moving Target: How Does an N-Methyl Group Impact Biological Activity?","authors":"Koay, Yen Chin; Richardson, Nicole L; Zaiter, Samantha S; Kho, Jessica; Nguyen, Sheena Y; Tran, Daniel H; Lee, Ka Wai; Buckton, Laura K; McAlpine, Shelli R","year":2016,"journal":"ChemMedChem, 11(8), 881-92","doi":"10.1002/cmdc.201500572","pmid":"26805515","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Incorporation and positional variation of an N-methyl moiety within cyclic peptides significantly alters their conformation, which in turn unpredictably affects cytotoxicity and binding affinity for the oncogenic regulator Hsp90.","whyItMatters":"Understanding how small chemical modifications like N-methylation affect peptide conformation and activity can guide the design of more effective peptide-based therapeutics targeting protein-protein interactions.","specificNumbers":"","methodology":"Seven cyclic peptides with varied N-methyl group positions were synthesized and tested for biological activity, including cytotoxicity and Hsp90 binding affinity, to assess how N-methyl placement influences function.","limitations":"The study does not specify the detailed biological models or sample sizes used, and the unpredictable nature of conformational changes may complicate rational drug design."},{"rthcId":"RPEP-02995","title":"NO system dependence of atropine-induced mydriasis and L-NAME- and L-arginine-induced miosis: Reversal by the pentadecapeptide BPC 157 in rats and guinea pigs.","authors":"Kokot, Antonio; Zlatar, Mirna; Stupnisek, Mirjana; Drmic, Domagoj; Radic, Radivoje; Vcev, Aleksandar; Seiwerth, Sven; Sikiric, Predrag","year":2016,"journal":"European journal of pharmacology, 771, 211-9","doi":"10.1016/j.ejphar.2015.12.016","pmid":"26698393","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BPC 157 administered locally (eye drops, 0.4 µg/eye) or systemically (intraperitoneal, 10 µg, 10 ng, or 10 pg/kg) had no effect on normal pupil size in either rats or guinea pigs. However, BPC 157 alone consistently counteracted atropine-induced mydriasis (pupil dilation) in both species and both routes of administration.\n\nIn its interactions with NO modulators, BPC 157 prolonged L-arginine-induced miosis (pupil constriction) and shortened L-NAME-induced miosis, demonstrating differential effects on the two arms of the NO system. When combined with L-NAME and/or L-arginine in atropine-dilated pupils, BPC 157 generally augmented their ability to counteract mydriasis. L-NAME and L-arginine independently produced miosis in normal pupils that was NO-specific (they attenuated each other when combined).","whyItMatters":"This study expands BPC 157’s known biological activities to include ocular control — a previously unexplored area. The finding that this peptide can reverse drug-induced pupil dilation through NO and cholinergic pathways suggests potential applications in ophthalmology. It also provides mechanistic insight into BPC 157’s interaction with the nitric oxide system, which is relevant to its broader proposed healing and protective properties.","specificNumbers":"","methodology":"Rats (Wistar) and guinea pigs received BPC 157, L-NAME (NOS inhibitor), L-arginine (NO precursor), and atropine either locally (eye drops) or systemically (intraperitoneal injection) alone or in various combinations. For normal pupil studies, treatments were given 3 minutes before assessment. For atropine studies, treatments were given at maximal mydriasis (30 minutes after 1% atropine drops). Multiple dose regimens of BPC 157 were tested (0.4 µg/eye locally; 10 µg, 10 ng, 10 pg/kg systemically).","limitations":"All research is preclinical in rats and guinea pigs. Exact sample sizes per group were not specified in the abstract. The study comes from a single research group (Sikiric lab) that has published extensively on BPC 157. No human data exists for BPC 157’s ocular effects. The mechanism (NO-mediated and cholinergic) is proposed but not fully elucidated at the molecular level. Multiple comparison corrections for the many treatment combinations were not described."},{"rthcId":"RPEP-02996","title":"Selank Inhibits Ethanol-Induced Hyperlocomotion and Manifestation of Behavioral Sensitization in DBA/2 Mice.","authors":"Kolik, L G; Nadorova, A V; Seredenin, S B","year":2016,"journal":"Bulletin of experimental biology and medicine, 162(1), 56-59","doi":null,"pmid":"27878720","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Selank administered intraperitoneally at 0.3 mg/kg prevented ethanol-induced hyperlocomotion and blocked the manifestation of motor sensitization in male DBA/2 mice, indicating modulation of ethanol's motivational effects.","whyItMatters":"Understanding how Selank modulates alcohol-induced behaviors could help develop new treatments for alcohol-related disorders and expand knowledge on peptide-based anxiolytics.","specificNumbers":"","methodology":"Male DBA/2 mice were given intraperitoneal injections of Selank, naloxone, or Afobazole before ethanol administration. Locomotor activity and behavioral sensitization were measured to assess the effects of these compounds on ethanol-induced stimulation.","limitations":"The study was conducted only in male DBA/2 mice, limiting generalizability to other strains, species, or females. The evidence strength and study type were not specified."},{"rthcId":"RPEP-02997","title":"Pharmacological characterization of the first in class clinical candidate PF-05190457: a selective ghrelin receptor competitive antagonist with inverse agonism that increases vagal afferent firing and glucose-dependent insulin secretion ex vivo.","authors":"Kong, J; Chuddy, J; Stock, I A; Loria, P M; Straub, S V; Vage, C; Cameron, K O; Bhattacharya, S K; Lapham, K; McClure, K F; Zhang, Y; Jackson, V M","year":2016,"journal":"British journal of pharmacology, 173(9), 1452-64","doi":"10.1111/bph.13439","pmid":"26784385","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"PF-05190457 acts as a potent and selective inverse agonist and competitive antagonist at the ghrelin receptor with a human Kd of 3 nM. It increases intracellular calcium in pancreatic islets and enhances vagal afferent firing in a glucose-dependent manner, effects comparable to glibenclamide and additive with GLP-1.","whyItMatters":"Blocking the ghrelin receptor may help reduce hunger and improve insulin secretion, offering a novel therapeutic approach for obesity and type 2 diabetes management.","specificNumbers":"","methodology":"The study used radioligand binding assays to measure drug affinity and functional assays including europium-labelled GTP binding, rat vagal afferent nerve recordings, and calcium imaging in isolated pancreatic islets to assess pharmacological activity ex vivo.","limitations":"The study was conducted ex vivo and in vitro, so in vivo effects and long-term safety in humans remain to be established."},{"rthcId":"RPEP-02998","title":"Neurologic Regulation and Orthodontic Tooth Movement.","authors":"Kyrkanides, Stephanos; Huang, Hechang; Faber, Richard D","year":2016,"journal":"Frontiers of oral biology, 18, 64-74","doi":"10.1159/000351900","pmid":"26599119","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Orthodontic tooth movement activates peripheral sensory nerve endings in the periodontium, which transmit pain signals to the trigeminal spinal nucleus, triggering c-Fos gene expression and concurrent inflammation involving astrocytes, microglia, and neurons.\n\nActivated periodontal sensory fibers release the neuropeptides Substance P and CGRP locally, which induce an inflammatory cascade that is essential for alveolar bone turnover and tooth movement. NSAIDs and other painkillers effectively reduce pain but also suppress this neurogenic inflammatory component, slowing bone turnover and consequently delaying orthodontic treatment progression.","whyItMatters":"Pain is the most disliked aspect of orthodontic treatment and affects nearly all patients. Understanding that neuropeptides serve a dual role — causing pain while also facilitating the bone remodeling needed for tooth movement — is crucial for developing pain management strategies that don't compromise treatment. This knowledge could guide the development of targeted approaches that control pain without affecting bone turnover.","specificNumbers":"","methodology":"Narrative review of published research on neurological mechanisms in orthodontic tooth movement, including nerve activation, neuropeptide release (Substance P, CGRP), nerve growth factor and TrkA receptor signaling, trigeminal spinal nucleus processing, neurogenic inflammation, and the effects of pain management on treatment outcomes.","limitations":"This is a narrative review that synthesizes existing research without presenting new experimental data. The specific quantitative impact of painkillers on orthodontic treatment duration is not well-established in controlled clinical trials. The review focuses on the neurogenic component of tooth movement without fully addressing other mechanical and cellular factors. Individual patient variation in neuropeptide responses is not discussed."},{"rthcId":"RPEP-02999","title":"Distinct roles of exogenous opioid agonists and endogenous opioid peptides in the peripheral control of neuropathy-triggered heat pain.","authors":"Labuz, Dominika; Celik, Melih Ö; Zimmer, Andreas; Machelska, Halina","year":2016,"journal":"Scientific reports, 6, 32799","doi":"10.1038/srep32799","pmid":"27605249","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In a chronic constriction injury model of neuropathic pain, exogenous opioid agonists (including peptidergic ligands) effectively reduced heat hypersensitivity when applied perineurally. However, endogenous opioid peptides β-endorphin, Met-enkephalin, and dynorphin A did not alleviate heat hypersensitivity — even when their release was triggered by corticotropin-releasing factor applied perineurally.\n\nCritically, exogenous opioids were equally effective in wild-type and opioid peptide-knockout mice, proving that endogenous opioids do not contribute to exogenous opioid analgesia in heat pain. Even when opioid peptides were applied exogenously (administered as drugs rather than released from immune cells), they were ineffective against heat pain. Conversely, endogenous opioid peptides did successfully relieve mechanical hypersensitivity, establishing a clear modality-specific distinction.","whyItMatters":"Neuropathic pain is notoriously difficult to treat, and understanding why some pain types respond to certain treatments while others don't is essential for developing better therapies. This study reveals that the body's immune-derived opioid peptide system — which was thought to be a general pain-relief mechanism — actually has modality-specific limits. This has direct implications for developing peripheral opioid therapies that could treat nerve pain without the side effects of systemic opioid drugs.","specificNumbers":"","methodology":"Chronic constriction injury of the sciatic nerve was performed in wild-type C57BL/6 mice and opioid peptide-knockout mice. Heat hypersensitivity was measured using the Hargreaves test and mechanical hypersensitivity with von Frey filaments. Exogenous opioid agonists and endogenous opioid peptides were applied perineurally. Corticotropin-releasing factor (which triggers opioid peptide secretion from leukocytes) was also tested. The use of opioid peptide-knockout mice allowed definitive assessment of endogenous opioid contributions.","limitations":"This is a mouse study using a single nerve injury model (chronic constriction injury), which may not represent all forms of neuropathic pain. The mechanisms by which exogenous opioids relieve heat pain while endogenous peptides cannot were not fully explained. Specific sample sizes per experimental group were not reported in the abstract. The study focused on acute drug administration rather than chronic treatment effects. Translation to human neuropathic pain requires clinical validation."},{"rthcId":"RPEP-03000","title":"Annular puncture with tumor necrosis factor-alpha injection enhances painful behavior with disc degeneration in vivo.","authors":"Lai, Alon; Moon, Andrew; Purmessur, Devina; Skovrlj, Branko; Laudier, Damien M; Winkelstein, Beth A; Cho, Samuel K; Hecht, Andrew C; Iatridis, James C","year":2016,"journal":"The spine journal : official journal of the North American Spine Society, 16(3), 420-31","doi":"10.1016/j.spinee.2015.11.019","pmid":"26610672","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Injection of tumor necrosis factor-alpha (TNFα) into rat intervertebral discs accelerated painful behavior and increased substance P expression in dorsal root ganglia, indicating enhanced pain signaling. Deeper annular punctures caused more severe disc degeneration, and painful behavior correlated with disc height loss and inflammatory state.","whyItMatters":"Understanding the role of inflammation and structural damage in discogenic pain can guide development of targeted treatments for back pain caused by disc degeneration. This model provides a way to study pain mechanisms and test new therapies.","specificNumbers":"","methodology":"The study used an in vivo rat model where lumbar discs were punctured at different depths and injected with saline, TNFα, or neurovascular growth factors (NGF and VEGF). Disc degeneration was assessed by X-ray, MRI, and histology, while pain was measured using Von Frey hyperalgesia tests and substance P immunostaining in dorsal root ganglia.","limitations":"The study used surgically induced disc injury in rats, which may not fully replicate human disc degeneration and pain. The evidence strength and study type were not specified, limiting generalizability."},{"rthcId":"RPEP-03001","title":"Increase of Mast Cell-Nerve Association and Neuropeptide Receptor Expression on Mast Cells in Perennial Allergic Rhinitis.","authors":"Le, Duc Dung; Schmit, David; Heck, Sebastian; Omlor, Albert Joachim; Sester, Martina; Herr, Christian; Schick, Bernhard; Daubeuf, François; Fähndrich, Sebastian; Bals, Robert; Frossard, Nelly; Al Kadah, Basel; Dinh, Quoc Thai","year":2016,"journal":"Neuroimmunomodulation, 23(5-6), 261-270","doi":"10.1159/000453068","pmid":"28030866","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The study demonstrated a significant increase in mast cell-nerve associations and elevated expression of neuropeptide receptors NK1R and NK2R on mast cells, particularly tryptase-chymase positive mast cells, in the nasal mucosa of patients with perennial allergic rhinitis. Additionally, nerve fibers expressed receptors PAR2 and TrkA, indicating bidirectional communication.","whyItMatters":"Understanding how mast cells and nerves communicate in allergic rhinitis can help develop treatments that modulate this interaction, potentially reducing inflammation and allergy symptoms.","specificNumbers":"","methodology":"Researchers used immunofluorescence and real-time PCR to examine human nasal mucosa samples, assessing mast cell and nerve fiber interactions and receptor expression levels in patients with allergic rhinitis compared to controls.","limitations":"The study type and evidence strength were not specified, and the sample size details were not provided, limiting assessment of generalizability. Functional outcomes of the increased receptor expression were not directly tested."},{"rthcId":"RPEP-03002","title":"Altered gut and adipose tissue hormones in overweight and obese individuals: cause or consequence?","authors":"Lean, M E J; Malkova, D","year":2016,"journal":"International journal of obesity (2005), 40(4), 622-32","doi":"10.1038/ijo.2015.220","pmid":"26499438","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Obese individuals show altered levels of peripheral appetite hormones such as GLP-1, CCK, PYY, ghrelin, pancreatic polypeptide, and leptin compared to lean individuals. Weight loss through diet or surgery modifies these hormone levels, with diet-induced weight loss potentially increasing appetite signals and bariatric surgery producing favorable hormonal changes that support sustained weight loss.","whyItMatters":"Understanding how appetite-regulating hormones change in obesity and after weight loss can guide development of targeted therapies to improve weight management and reduce obesity-related health risks.","specificNumbers":"","methodology":"This article is a literature review summarizing research on peripheral appetite hormones in obesity and their changes following weight loss interventions including diet, exercise, and bariatric surgery.","limitations":"The review does not provide new experimental data and the evidence strength and study types of included research vary, limiting definitive conclusions about causality or treatment efficacy."},{"rthcId":"RPEP-03003","title":"MOTS-c: A novel mitochondrial-derived peptide regulating muscle and fat metabolism.","authors":"Lee, Changhan; Kim, Kyung Hwa; Cohen, Pinchas","year":2016,"journal":"Free radical biology & medicine, 100, 182-187","doi":"10.1016/j.freeradbiomed.2016.05.015","pmid":"27216708","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"MOTS-c, a mitochondrial-derived peptide encoded by mitochondrial DNA, targets skeletal muscle to enhance glucose metabolism and regulate fat metabolism. This peptide represents a novel mitochondrial signaling mechanism with potential roles in obesity, diabetes, exercise, and longevity.","whyItMatters":"Discovering MOTS-c expands our understanding of mitochondrial signaling in metabolism, offering new targets for treating metabolic disorders and improving muscle function.","specificNumbers":"","methodology":"The study reviewed existing research on mitochondrial DNA-encoded peptides, focusing on MOTS-c’s biological activities and metabolic effects, particularly its role in skeletal muscle glucose metabolism.","limitations":"The study is primarily a review and does not provide new experimental data; the exact mechanisms and clinical applications of MOTS-c require further investigation."},{"rthcId":"RPEP-03004","title":"Light-emitting diodes downregulate cathelicidin, kallikrein and toll-like receptor 2 expressions in keratinocytes and rosacea-like mouse skin.","authors":"Lee, Jee-Bum; Bae, Soo Hyeon; Moon, Ki Rang; Na, Eui Young; Yun, Sook Jung; Lee, Seung-Chul","year":2016,"journal":"Experimental dermatology, 25(12), 956-961","doi":"10.1111/exd.13133","pmid":"27315464","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"LED irradiation at 630 nm and 940 nm significantly downregulated mRNA expressions of cathelicidin (LL-37), kallikrein 5 (KLK5), and toll-like receptor 2 (TLR-2) in cultured normal human epidermal keratinocytes and rosacea-like mouse skin. Protease activity was also significantly suppressed at these wavelengths, indicating reduced inflammatory activity.","whyItMatters":"Understanding how LED light affects inflammatory mediators in rosacea could lead to non-invasive, light-based treatments that reduce symptoms without drugs. This offers a potential new approach for managing chronic skin inflammation.","specificNumbers":"","methodology":"The study used cultured normal human epidermal keratinocytes treated to induce inflammatory mediators and rosacea-like mouse skin models. Cells and mice were exposed to LED irradiation at wavelengths ranging from 480 to 940 nm and various fluences. Molecular analyses including RT-PCR, real-time PCR, immunofluorescence, and enzyme-linked immunosorbent assays measured changes in inflammatory markers and protease activity.","limitations":"The study was conducted in vitro and in mouse models, so results may not fully translate to humans. Clinical trials are needed to confirm safety and effectiveness in rosacea patients."},{"rthcId":"RPEP-03005","title":"Oxytocin for the treatment of drug and alcohol use disorders.","authors":"Lee, Mary R; Weerts, Elise M","year":2016,"journal":"Behavioural pharmacology, 27(8), 640-648","doi":null,"pmid":"27603752","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03006","title":"Efficacy of a Complex of 5-Aminolevulinic Acid and Glycyl-Histidyl-Lysine Peptide on Hair Growth.","authors":"Lee, Weon Ju; Sim, Hyun Bo; Jang, Yong Hyun; Lee, Seok-Jong; Kim, Do Won; Yim, Soon-Ho","year":2016,"journal":"Annals of dermatology, 28(4), 438-43","doi":"10.5021/ad.2016.28.4.438","pmid":"27489425","tags":[],"studyType":"Randomized Controlled Trial","evidenceStrength":"moderate","keyFinding":"A topical complex of 5-aminolevulinic acid (5-ALA) and GHK peptide (ALAVAX) significantly increased hair count in men with pattern hair loss over 6 months compared to placebo. The 50 mg/ml group showed the strongest results, with a mean increase of 71.5 hairs (p<0.05) versus only 9.6 hairs in the placebo group. The ratio of change in hair count between the 50 mg/ml group (2.38) and placebo (1.21) was statistically significant (p<0.05).\n\nInterestingly, the higher-dose 100 mg/ml group showed a hair count increase of 52.6, which was also significant versus baseline but numerically lower than the 50 mg/ml group. Patient satisfaction was highest in the 100 mg/ml group (26.7% reporting good or better), though hair length and thickness did not significantly differ among groups. No adverse events were reported in any group.","whyItMatters":"Male pattern hair loss affects a large proportion of men and current treatments like finasteride and minoxidil have limitations. This study suggests that a peptide-based topical approach using GHK combined with 5-ALA could offer a complementary treatment option with no reported side effects, which is notable given that existing treatments can carry significant adverse effects.","specificNumbers":"n=45 · 6-month treatment · Hair count increase: 71.5 (50 mg/ml) vs 9.6 (placebo) · p<0.05 · 0 adverse events","methodology":"Randomized, placebo-controlled trial with 45 men with male pattern hair loss divided into three groups: ALAVAX 100 mg/ml (group A), ALAVAX 50 mg/ml (group B), and placebo (group C). Treatment was applied once daily for 6 months. Outcomes measured at months 1, 3, and 6 included total hair count, hair length, hair thickness, patient satisfaction, and adverse events.","limitations":"Small sample size of only 45 participants across three groups. Hair length and thickness did not show significant changes, suggesting the treatment may primarily affect hair count rather than hair quality. The lower-dose group outperformed the higher-dose group on hair count, which is unusual and unexplained. Single-center study with no long-term follow-up beyond 6 months."},{"rthcId":"RPEP-03007","title":"Simultaneous Stabilization and Multimerization of a Peptide α-Helix by Stapling Polymerization.","authors":"Lee, Young-Joo; Han, Sanghun; Lim, Yong-Beom","year":2016,"journal":"Macromolecular rapid communications, 37(13), 1021-6","doi":"10.1002/marc.201600179","pmid":"27162197","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The stapling polymerization technique using radical polymerization between acryloylated peptide side chains and vinylic monomers effectively stabilizes α-helical conformations via i, i+7 crosslinking and produces multimeric peptide-polyacrylamide conjugates containing approximately 3 to 16 peptides each.","whyItMatters":"Stabilizing peptide α-helices and creating multimeric forms can enhance the potency and specificity of peptide-based therapeutics and biomolecular tools, potentially improving drug design and biological modulation.","specificNumbers":"","methodology":"The study employed a one-pot radical polymerization method to crosslink acryloylated peptides with vinylic monomers, testing different crosslinking positions (i, i+4 vs. i, i+7) on model peptides to assess α-helix stabilization and multimer formation.","limitations":"The study's evidence strength and detailed biological efficacy data are not provided, and the approach was demonstrated primarily on model peptides rather than complex biological systems."},{"rthcId":"RPEP-03008","title":"The two fold role of oxytocin in social developmental disorders: A cause and a remedy?","authors":"Lefevre, Arthur; Sirigu, Angela","year":2016,"journal":"Neuroscience and biobehavioral reviews, 63, 168-76","doi":"10.1016/j.neubiorev.2016.01.011","pmid":"26828138","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Early oxytocin administration may be associated with social developmental impairments such as autism spectrum disorders, but oxytocin also shows potential to improve social behaviors in ASD patients. Animal studies reveal contradictory effects of chronic oxytocin exposure, highlighting complex biological mechanisms.","whyItMatters":"Understanding oxytocin's dual role is crucial for safely using it in obstetrics and exploring its therapeutic potential for social impairments in autism.","specificNumbers":"","methodology":"This article is a literature review analyzing recent animal and human studies on the long-term effects of neonatal and chronic oxytocin administration on social development and autism spectrum disorders.","limitations":"The evidence is largely based on animal studies with contradictory results, and human data are methodologically limited, making definitive conclusions difficult."},{"rthcId":"RPEP-03009","title":"Neuropeptide Y input to the rat basolateral amygdala complex and modulation by conditioned fear.","authors":"Leitermann, Randy J; Rostkowski, Amanda B; Urban, Janice H","year":2016,"journal":"The Journal of comparative neurology, 524(12), 2418-39","doi":"10.1002/cne.23960","pmid":"26779765","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The study identified that NPY projections to the basolateral amygdala originate mainly from the amygdalostriatal transition area and bed nucleus of the stria terminalis, with a distinct subpopulation coexpressing somatostatin. Conditioned fear increased NPY gene expression specifically in the amygdalostriatal transition area, indicating its role in fear regulation.","whyItMatters":"Understanding the sources and regulation of NPY in fear-related brain circuits can inform peptide-based strategies to modulate anxiety and fear disorders.","specificNumbers":"","methodology":"Researchers used anatomical tracing with Fluorogold combined with immunohistochemistry to map NPY fibers projecting to the basolateral amygdala in rats. They also examined coexpression of NPY with somatostatin and catecholaminergic markers and measured changes in NPY gene expression after a conditioned fear paradigm.","limitations":"The study was conducted in rats, so findings may not fully translate to humans; also, the functional effects of these NPY projections were not directly tested."},{"rthcId":"RPEP-03010","title":"The neuropilin-1 receptor mediates enhanced tumor delivery of H2K polyplexes.","authors":"Leng, Qixin; Mixson, A James","year":2016,"journal":"The journal of gene medicine, 18(7), 134-44","doi":"10.1002/jgm.2886","pmid":"27257039","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The neuropilin-1 receptor (NRP-1) mediates enhanced tumor delivery of H2K polyplexes, with blocking NRP-1 reducing tumor luciferase activity by 96%, indicating NRP-1-dependent transcytosis facilitates widespread tumor transfection.","whyItMatters":"Understanding how peptides like H2K enter tumors can improve gene therapy delivery systems, potentially making cancer treatments more effective and targeted.","specificNumbers":"","methodology":"The study synthesized linear and branched histidine-lysine peptides and tested their ability to lyse endosomes and transfect tumor xenografts in mice. The role of NRP-1 was assessed by blocking the receptor with antibodies and measuring gene expression via luciferase activity.","limitations":"The study was conducted in tumor xenograft mouse models, which may not fully replicate human tumor biology. The exact molecular mechanisms of NRP-1 mediated transcytosis require further elucidation."},{"rthcId":"RPEP-03011","title":"Protective Effects of Antioxidant Peptide SS-31 Against Multiple Organ Dysfunctions During Endotoxemia.","authors":"Li, Guoming; Wu, Jing; Li, Renqi; Yuan, Dong; Fan, Yunxia; Yang, Jianjun; Ji, Muhuo; Zhu, Sihai","year":2016,"journal":"Inflammation, 39(1), 54-64","doi":"10.1007/s10753-015-0222-1","pmid":"26231114","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"SS-31 administration significantly improved sepsis-induced organ dysfunctions, reduced oxidative stress markers, proinflammatory cytokines, and apoptosis, and increased survival in a cecal ligation and puncture sepsis model.","whyItMatters":"This study suggests that targeting mitochondrial oxidative stress with SS-31 could be a promising therapeutic strategy to prevent organ failure in sepsis, a major cause of death in critical care.","specificNumbers":"","methodology":"Sepsis was induced in animals using cecal ligation and puncture. SS-31 (5 mg/kg) or vehicle was administered intraperitoneally immediately and 5 hours after surgery. Various biochemical, histological, and survival analyses were performed to assess organ function and inflammation.","limitations":"The study used an animal model, so results may not fully translate to humans. The exact molecular mechanisms of SS-31’s protective effects require further elucidation."},{"rthcId":"RPEP-03012","title":"Selected Biomarkers Revealed Potential Skin Toxicity Caused by Certain Copper Compounds.","authors":"Li, Hairui; Toh, Pei Zhen; Tan, Jia Yao; Zin, Melvin T; Lee, Chi-Ying; Li, Bo; Leolukman, Melvina; Bao, Hongqian; Kang, Lifeng","year":2016,"journal":"Scientific reports, 6, 37664","doi":"10.1038/srep37664","pmid":"27892491","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Copper chloride (CuCl2) and copper acetate (Cu(OAc)2) significantly upregulated skin irritation biomarkers IL-1α, IL-8, HSPA1A, and FOSL1 at 58 and 580 μM concentrations without reducing cell viability, indicating potential skin irritation. In contrast, GHK-Cu showed no cytotoxicity or significant changes in these biomarkers, suggesting a low irritation potential.","whyItMatters":"Understanding which copper compounds cause skin irritation helps develop safer copper-based skin treatments. GHK-Cu’s low irritation potential supports its use as a safer copper delivery method in skincare products.","specificNumbers":"","methodology":"The study used a keratinocyte-based in vitro model to assess skin irritation potential of three copper compounds. Cell viability and cytotoxicity were measured using tetrazolium reduction and LDH assays. Gene expression and protein levels of skin irritation biomarkers were analyzed by real-time PCR and protein quantification after 24-hour treatments.","limitations":"The study used an in vitro keratinocyte model which may not fully replicate complex skin responses in living humans. The evidence strength and study type were not specified, limiting assessment of clinical relevance."},{"rthcId":"RPEP-03013","title":"Roles of d-Amino Acids on the Bioactivity of Host Defense Peptides.","authors":"Li, Hao; Anuwongcharoen, Nuttapat; Malik, Aijaz Ahmad; Prachayasittikul, Virapong; Wikberg, Jarl E S; Nantasenamat, Chanin","year":2016,"journal":"International journal of molecular sciences, 17(7)","doi":"10.3390/ijms17071023","pmid":"27376281","tags":[],"studyType":"review","evidenceStrength":"n/a","keyFinding":"This is the first systematic review dedicated to how incorporating D-amino acids (mirror-image building blocks) improves host defense peptides (HDPs). D-amino acid substitution consistently enhances HDPs by increasing resistance to enzymatic degradation, improving antimicrobial potency, and maintaining or broadening activity against bacteria and tumors. The review systematically catalogs the effects of D-AA incorporation across different HDP families, filling a gap in the literature where this strategy was frequently mentioned but never comprehensively analyzed.","whyItMatters":"Host defense peptides are promising alternatives to conventional antibiotics in an era of rising drug resistance, but their clinical use is limited by rapid degradation in the body. D-amino acid substitution is one of the most reliable strategies to overcome this problem. By systematically reviewing all available evidence, this paper provides researchers with a roadmap for designing more stable and effective antimicrobial peptides.","specificNumbers":"","methodology":"Systematic review of published literature on D-amino acid incorporation in host defense peptides, covering effects on antimicrobial activity, stability, structure, and selectivity across multiple HDP families.","limitations":"This is a review article without original experimental data. The field of D-amino acid peptide modification is heavily studied in vitro, with limited in vivo or clinical data. The review may not capture all the nuances of how D-AA substitution at different positions affects different peptide families differently."},{"rthcId":"RPEP-03014","title":"Entry of hepatitis B and hepatitis D virus into hepatocytes: Basic insights and clinical implications.","authors":"Li, Wenhui; Urban, Stephan","year":2016,"journal":"Journal of hepatology, 64(1 Suppl), S32-S40","doi":"10.1016/j.jhep.2016.02.011","pmid":"27084034","tags":["antiviral-peptides","hepatitis"],"studyType":"review","evidenceStrength":"expert-review","keyFinding":"After nearly 30 years of mystery, researchers identified NTCP (sodium taurocholate co-transporting polypeptide) as the liver-specific receptor that hepatitis B and hepatitis D viruses use to enter liver cells. This discovery opened four major research directions:\n\n1. NTCP-expressing cell lines now allow researchers to study the full HBV replication cycle from its natural template (cccDNA) in the lab.\n2. These cell systems enable high-throughput drug screening to find new anti-HBV treatments.\n3. Animals engineered to express human NTCP provide new in vivo models for studying these uniquely human infections.\n4. The peptide entry inhibitor Myrcludex B (bulevirtide) proved that blocking NTCP can prevent viral entry — a clinical proof-of-concept for this therapeutic approach.","whyItMatters":"Hepatitis B chronically infects approximately 300 million people worldwide and causes nearly 900,000 deaths per year from liver cancer and cirrhosis. Current treatments suppress but rarely cure the virus. The discovery of NTCP as the entry receptor — and the peptide drug Myrcludex B (now approved as bulevirtide/Hepcludex) that blocks it — represents one of the most successful examples of receptor discovery leading directly to a new class of peptide-based antiviral drugs. It's also the first effective treatment specifically for hepatitis D, which was previously untreatable.","specificNumbers":"~30 years from HBV discovery to receptor identification · NTCP identified as receptor for both HBV and HDV · Myrcludex B = clinical proof-of-concept entry inhibitor · Platform enables high-throughput drug screening","methodology":"Expert review article covering the historical progression from unknown HBV entry mechanisms to NTCP receptor identification, including the development of cell culture systems, identification of viral determinants of infectivity, and clinical translation through the peptide entry inhibitor Myrcludex B.","limitations":"As a review, this synthesizes existing knowledge rather than presenting new data. At the time of publication (2016), Myrcludex B was still in clinical trials (it has since been approved). The review predates some of the latest clinical outcome data. NTCP-based therapies block entry of new viruses but don't eliminate existing viral DNA reservoirs in liver cells."},{"rthcId":"RPEP-03015","title":"Incretin-based therapy for type 2 diabetes mellitus is promising for treating neurodegenerative diseases.","authors":"Li, Yanwei; Li, Lin; Hölscher, Christian","year":2016,"journal":"Reviews in the neurosciences, 27(7), 689-711","doi":"10.1515/revneuro-2016-0018","pmid":"27276528","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Protease-resistant GLP-1 mimetics including lixisenatide, liraglutide, and exenatide have demonstrated neuroprotective effects in preclinical models of neurodegenerative disease and shown first positive results in clinical trials for both Alzheimer's disease and Parkinson's disease patients.\n\nBeyond single-target GLP-1 agonists, the review identified promising preclinical evidence for GIP agonists, DPP-IV inhibitors, oxyntomodulin, dual GLP-1/GIP agonists, and triple GLP-1/GIP/glucagon receptor agonists in neurodegenerative disease models. The shared mechanism of insulin dysregulation between diabetes and neurodegeneration provides a biological rationale for this therapeutic approach.","whyItMatters":"Alzheimer's and Parkinson's diseases have very limited treatment options despite affecting tens of millions worldwide. The realization that diabetes drugs targeting incretin peptide pathways could protect the brain opens up an entirely new therapeutic strategy — one that leverages drugs already proven safe in diabetic patients, potentially accelerating the path to approved treatments for neurodegeneration.","specificNumbers":"","methodology":"This is a narrative review article that synthesized evidence from preclinical animal studies and early-phase human clinical trials investigating the effects of various incretin-based therapies on neurodegenerative diseases. The review covers multiple drug classes and disease models to provide a comprehensive overview of the field.","limitations":"Most evidence comes from preclinical animal studies, which frequently do not translate to human efficacy. The clinical trial data available at the time of publication was from early-phase, small-scale studies. The review does not provide a systematic or quantitative analysis (meta-analysis) of the evidence. Published in 2016, it does not capture more recent clinical trial results. The mechanisms linking diabetes and neurodegeneration, while plausible, are not fully proven."},{"rthcId":"RPEP-03016","title":"Intestinal Metrnl released into the gut lumen acts as a local regulator for gut antimicrobial peptides.","authors":"Li, Zhi-Yong; Fan, Mao-Bing; Zhang, Sai-Long; Qu, Yi; Zheng, Si-Li; Song, Jie; Miao, Chao-Yu","year":2016,"journal":"Acta pharmacologica Sinica, 37(11), 1458-1466","doi":"10.1038/aps.2016.70","pmid":"27546006","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Metrnl is predominantly expressed in intestinal epithelial cells in both humans and mice, and it is mainly released into the gut lumen rather than the bloodstream. When researchers knocked out Metrnl specifically in intestinal epithelial cells, gut fluid Metrnl levels dropped significantly while serum levels were only marginally affected. The knockout mice showed decreased expression of key antimicrobial peptides Reg3g and lactotransferrin, but no changes in body weight, food intake, blood glucose, colon length, intestinal permeability, or mucus content under normal conditions.","whyItMatters":"This study reveals Metrnl as a previously unknown regulator of gut antimicrobial peptides, which are the intestine's first line of defense against harmful bacteria. Understanding how the gut maintains its antimicrobial peptide arsenal could lead to new strategies for treating intestinal infections or inflammatory bowel conditions where these defenses break down.","specificNumbers":"69 human donors · 19 tissue types screened · 14 mouse tissue types tested · gut-specific Metrnl knockout · decreased Reg3g and lactotransferrin expression","methodology":"Researchers used a human tissue microarray from 69 donors across 19 tissue types to map where Metrnl is expressed, then confirmed findings in fresh human and mouse tissues. They created intestinal epithelial cell-specific Metrnl knockout mice to determine Metrnl's functional role, measuring gut fluid and serum Metrnl levels, body weight, food intake, blood glucose, colon histology, intestinal permeability, mucus content, and antimicrobial peptide expression.","limitations":"The study only examined effects under normal physiological conditions — it did not test whether the reduced antimicrobial peptides make the knockout mice more vulnerable to infection or intestinal inflammation. The serum Metrnl reduction was not statistically significant, leaving uncertainty about systemic effects. As a mouse study, direct translation to human physiology requires further validation."},{"rthcId":"RPEP-03017","title":"Tryptase and Protease-Activated Receptor 2 Expression Levels in Irritable Bowel Syndrome.","authors":"Liang, Wen-Jing; Zhang, Guo; Luo, He-Sheng; Liang, Lie-Xin; Huang, Dan; Zhang, Fa-Can","year":2016,"journal":"Gut and liver, 10(3), 382-90","doi":"10.5009/gnl14319","pmid":"26446924","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The study demonstrated significantly elevated mRNA and protein levels of tryptase and PAR-2 in colon biopsies from IBS patients compared to healthy controls. Additionally, increased mast cells and neuropeptides (CGRP, VIP, SP) were observed in IBS-D patients, suggesting that tryptase may activate PAR-2, leading to neuropeptide release and symptom manifestation.","whyItMatters":"Understanding the molecular changes in IBS can help identify new therapeutic targets, such as blocking tryptase or PAR-2, to alleviate symptoms and improve patient outcomes.","specificNumbers":"","methodology":"Colonoscopic biopsies were collected from 38 subjects including IBS-D, IBS-C, and healthy controls. Real-time PCR and Western blot analyzed tryptase and PAR-2 expression, immunohistochemistry measured neuropeptides, and mast cells were counted using toluidine blue staining.","limitations":"The study had a relatively small sample size and did not clarify the causal relationship between increased tryptase/PAR-2 and IBS symptoms. The study type and evidence strength were not specified."},{"rthcId":"RPEP-03018","title":"Ghrelin and the Cardiovascular System.","authors":"Lilleness, Brian M; Frishman, William H","year":2016,"journal":"Cardiology in review, 24(6), 288-297","doi":null,"pmid":"27465535","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03019","title":"Impact of Axis of GHRH and GHRH Receptor on Cell Viability and Apoptosis of the Placental Choriocarcinoma Cell Line.","authors":"Liu, A-X; Zhang, D; Zhu, Y-M; Gao, H-J; Jiang, J-Y; Hu, X-L; Lv, P-P; Leung, P C K; Huang, H-F","year":2016,"journal":"Current molecular medicine, 16(3), 299-311","doi":null,"pmid":"26917260","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The expression of GHRH-R is significantly lower in placental tissues from early pregnancy loss compared to normal controls. Inhibition of GHRH-R with the antagonist JMR-132 in JEG-3 cells reduces cell viability and induces apoptosis through activation of caspase-3, p38, and p53 pathways, and by increasing ER stress markers such as GRP78 and phospho-eIF2α while inhibiting Akt phosphorylation.","whyItMatters":"Understanding how GHRH-R regulates placental cell survival and death could reveal targets for treating placental dysfunction and related pregnancy complications. It also advances knowledge of peptide hormone signaling in placental development.","specificNumbers":"","methodology":"The study measured GHRH-R expression in human placental villous tissues and JEG-3 placental choriocarcinoma cells. It then treated JEG-3 cells with the GHRH antagonist JMR-132 and assessed effects on cell viability, apoptosis, and related signaling pathways using molecular assays. Additional experiments involved pretreatment with salubrinal and GHRH-R knockdown to confirm pathway involvement.","limitations":"The study used a placental cancer cell line (JEG-3), which may not fully represent normal placental cells. The exact clinical implications for pregnancy loss require further validation in vivo and in human subjects."},{"rthcId":"RPEP-03020","title":"Identification of a Short Cell-Penetrating Peptide from Bovine Lactoferricin for Intracellular Delivery of DNA in Human A549 Cells.","authors":"Liu, Betty R; Huang, Yue-Wern; Aronstam, Robert S; Lee, Han-Jung","year":2016,"journal":"PloS one, 11(3), e0150439","doi":"10.1371/journal.pone.0150439","pmid":"26942714","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The L5a cell-penetrating peptide (sequence RRWQW) from bovine lactoferricin efficiently forms stable complexes with plasmid DNA at an optimal nitrogen/phosphate ratio of 12, enabling effective intracellular delivery and expression of enhanced green fluorescent protein (EGFP) in human A549 lung cancer cells without cytotoxicity.","whyItMatters":"This discovery provides a shorter, less immunogenic alternative to existing cell-penetrating peptides for gene delivery, which could improve the safety and efficiency of gene therapy techniques.","specificNumbers":"","methodology":"The study prepared noncovalent complexes of the L5a peptide with plasmid DNA encoding EGFP and transfected human A549 cells. Gene expression was assessed by real-time PCR and fluorescence microscopy. Zeta-potential measurements analyzed electrostatic interactions, and cytotoxicity was evaluated to ensure safety.","limitations":"The study was conducted in vitro using a single human lung cancer cell line, so further research is needed to confirm efficacy and safety in other cell types and in vivo models."},{"rthcId":"RPEP-03021","title":"The efficacy of thymosin α1 as immunomodulatory treatment for sepsis: a systematic review of randomized controlled trials.","authors":"Liu, Fang; Wang, Hong-Mei; Wang, Tiansheng; Zhang, Ya-Mei; Zhu, Xi","year":2016,"journal":"BMC infectious diseases, 16, 488","doi":"10.1186/s12879-016-1823-5","pmid":"27633969","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03022","title":"Study on the molecular mechanism of antinociception induced by ghrelin in acute pain in mice.","authors":"Liu, Fu-Yan; Zhang, Min-Min; Zeng, Ping; Liu, Wen-Wen; Wang, Jing-Lei; Yang, Bei; Dai, Qun; Wei, Jie","year":2016,"journal":"Peptides, 83, 1-7","doi":"10.1016/j.peptides.2016.07.006","pmid":"27474249","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Intracerebroventricular injection of ghrelin induces antinociception in mice by initially activating GHS-R1α, which increases the release of endogenous proenkephalin (PENK) peptides that activate δ-opioid receptors (OPRD), mediating the analgesic effect.","whyItMatters":"Identifying how ghrelin modulates pain through opioid receptors provides insight into novel pain management strategies that could avoid the side effects of traditional opioids.","specificNumbers":"","methodology":"The study used intracerebroventricular (i.c.v.) injections of ghrelin and receptor-specific antagonists and agonists in mice to investigate the involvement of GHS-R1α and δ-opioid receptors in pain relief. Molecular analyses measured mRNA and protein levels of relevant peptides and receptors.","limitations":"The study was conducted only in mice and used intracerebroventricular injections, which may not directly translate to humans or practical clinical administration routes."},{"rthcId":"RPEP-03023","title":"Substance P Promotes the Proliferation, but Inhibits Differentiation and Mineralization of Osteoblasts from Rats with Spinal Cord Injury via RANKL/OPG System.","authors":"Liu, Hai-Juan; Yan, Hua; Yan, Jun; Li, Hao; Chen, Liang; Han, Li-Ren; Yang, Xiao-Fei","year":2016,"journal":"PloS one, 11(10), e0165063","doi":"10.1371/journal.pone.0165063","pmid":"27764190","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Substance P promotes proliferation but inhibits differentiation and mineralization of osteoblasts derived from bone marrow mesenchymal stem cells in rats with spinal cord injury. This effect is mediated via the RANKL/OPG system, leading to increased bone resorption and osteoporosis.","whyItMatters":"Understanding how substance P disrupts bone cell function after spinal cord injury helps identify potential targets to prevent osteoporosis in these patients. It highlights the role of neuropeptides in bone metabolism regulation.","specificNumbers":"","methodology":"The study used bone marrow mesenchymal stem cell-derived osteoblast cultures from spinal cord injured and sham-operated rats. Expression of NK1R receptors was analyzed by immunohistochemistry and Western blot. Effects of various concentrations of substance P on osteoblast proliferation, differentiation, mineralization, and RANKL/OPG expression were assessed in vitro.","limitations":"The study was conducted in rats and in vitro cell cultures, so results may not fully translate to humans. The exact clinical relevance and long-term effects of modulating substance P remain to be established."},{"rthcId":"RPEP-03024","title":"Synthesized peptides 705-734 from hepatitis C virus E2 glycoprotein induce dendritic cell maturation by activating p38 MAPK signaling.","authors":"Liu, Xiaojing; Chen, Na; Lin, Shumei; Liu, Min","year":2016,"journal":"International immunopharmacology, 30, 194-201","doi":"10.1016/j.intimp.2015.11.009","pmid":"26604090","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The synthesized 30 amino acid peptide (residues 705-734) from HCV E2 binds to dendritic cells via the DC-SIGN receptor, induces their maturation, increases IL-12, CD80, and CD86 production, decreases IL-10, and activates p38 MAPK signaling.","whyItMatters":"Understanding how HCV peptides activate immune cells helps identify new targets for vaccines or inhibitors, potentially improving hepatitis C treatment and prevention.","specificNumbers":"","methodology":"The study synthesized a 30 amino acid peptide from HCV E2 using solid-phase peptide synthesis. Western blot and infection blocking assays confirmed peptide characteristics. ELISA and flow cytometry assessed dendritic cell responses and T cell activation after peptide treatment.","limitations":"The study did not specify the sample size or in vivo validation, limiting understanding of clinical relevance. The exact signaling mechanisms require further exploration."},{"rthcId":"RPEP-03025","title":"Effects of Diclofenac, L-NAME, L-Arginine, and Pentadecapeptide BPC 157 on Gastrointestinal, Liver, and Brain Lesions, Failed Anastomosis, and Intestinal Adaptation Deterioration in 24 Hour-Short-Bowel Rats.","authors":"Lojo, Nermin; Rasic, Zarko; Zenko Sever, Anita; Kolenc, Danijela; Vukusic, Darko; Drmic, Domagoj; Zoricic, Ivan; Sever, Marko; Seiwerth, Sven; Sikiric, Predrag","year":2016,"journal":"PloS one, 11(9), e0162590","doi":"10.1371/journal.pone.0162590","pmid":"27627764","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BPC 157 completely ameliorated symptoms in short-bowel rats across all experimental conditions: surgery alone, surgery plus diclofenac, and surgery plus diclofenac plus the NOS blocker L-NAME. This included protection of anastomosis healing, restoration of intestinal adaptation, and reduction of gastrointestinal, liver, and brain lesions.\n\nThe damage cascade was dose-dependent: surgery alone caused mild stomach/duodenum lesions with severe brain lesions; adding diclofenac (12 mg/kg) caused widespread severe lesions across all organs; adding L-NAME on top made everything worse with macro/microscopic necrosis. BPC 157 at both 10 μg/kg and 10 ng/kg reversed all of these. L-arginine only helped reverse L-NAME-specific aggravation.","whyItMatters":"Major bowel surgery carries significant risks of complications including anastomosis failure, organ damage, and impaired intestinal adaptation. NSAIDs like diclofenac, commonly used for post-surgical pain, can worsen these outcomes. BPC 157’s ability to protect multiple organ systems simultaneously — gut, liver, and brain — through what appears to involve the COX-NO system suggests it could be a valuable therapeutic agent for post-surgical recovery, particularly in situations where NSAID use is necessary.","specificNumbers":"","methodology":"Wistar rats underwent massive small bowel resection with anastomosis creation. Immediately after surgery, rats were given intraperitoneal injections of diclofenac (12 mg/kg), BPC 157 (10 μg/kg or 10 ng/kg), L-NAME (5 mg/kg), L-arginine (100 mg/kg), alone or in combinations. Animals were assessed 24 hours later for anastomosis healing quality, intestinal adaptation, and macro/microscopic lesions in the gastrointestinal tract, liver, and brain (cerebrum, hippocampus, cerebellum).","limitations":"This is an animal study with only a 24-hour follow-up period, which cannot predict long-term outcomes or human responses. The sample size per group is not specified in the abstract. The research comes from a single lab group (Sikiric et al.) that produces the majority of BPC 157 research, limiting independent replication. The mechanisms by which BPC 157 achieves such broad protective effects remain incompletely understood. No human surgical studies with BPC 157 exist."},{"rthcId":"RPEP-03026","title":"The Effect of Teriparatide on Fracture Healing of Osteoporotic Patients: A Meta-Analysis of Randomized Controlled Trials.","authors":"Lou, Shenghan; Lv, Houchen; Wang, Guoqi; Zhang, Licheng; Li, Ming; Li, Zhirui; Zhang, Lihai; Tang, Peifu","year":2016,"journal":"BioMed research international, 2016, 6040379","doi":"10.1155/2016/6040379","pmid":"27429980","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03027","title":"Rational Design of Calpain Inhibitors Based on Calpastatin Peptidomimetics.","authors":"Low, Kristin E; Ler, Spencer; Chen, Kevin J; Campbell, Robert L; Hickey, Jennifer L; Tan, Joanne; Scully, Conor C G; Davies, Peter L; Yudin, Andrei K; Zaretsky, Serge","year":2016,"journal":"Journal of medicinal chemistry, 59(11), 5403-15","doi":"10.1021/acs.jmedchem.6b00267","pmid":"27148623","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Four cyclic peptidomimetic compounds exhibited low micromolar inhibition of calpain-2, with improved potency and selectivity over other cysteine proteases. The study identified both competitive and mixed inhibition mechanisms, including an allosteric site for noncompetitive inhibition.","whyItMatters":"Calpain enzymes are implicated in many diseases, so developing selective inhibitors can lead to targeted therapies with fewer side effects. This study advances peptide-based drug design by providing potent and selective calpain inhibitors.","specificNumbers":"","methodology":"A library of 45 cyclic peptide compounds based on a β-turn loop sequence from calpastatin was synthesized using aziridine aldehyde-mediated macrocyclization. These compounds were tested for inhibitory activity against calpain-2 and other cysteine proteases, and inhibition constants (Ki) were calculated to assess potency and selectivity.","limitations":"The study does not specify in vivo efficacy or toxicity data, and the exact clinical relevance of these inhibitors remains to be established. The evidence strength and study type were not clearly defined."},{"rthcId":"RPEP-03028","title":"Administration of antioxidant peptide SS-31 attenuates transverse aortic constriction-induced pulmonary arterial hypertension in mice.","authors":"Lu, Hung-I; Huang, Tien-Hung; Sung, Pei-Hsun; Chen, Yung-Lung; Chua, Sarah; Chai, Han-Yan; Chung, Sheng-Ying; Liu, Chu-Feng; Sun, Cheuk-Kwan; Chang, Hsueh-Wen; Zhen, Yen-Yi; Lee, Fan-Yen; Yip, Hon-Kan","year":2016,"journal":"Acta pharmacologica Sinica, 37(5), 589-603","doi":"10.1038/aps.2015.162","pmid":"27063219","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The mitochondria-targeting antioxidant peptide SS-31 (2 mg/day IP for 60 days) significantly reduced right ventricular systolic blood pressure and lung injury in mice with TAC-induced pulmonary arterial hypertension. SS-31 simultaneously improved multiple disease pathways: it decreased oxidative stress (NOX-1/NOX-2), inflammation (MMP-9/TNF-α/iNOS), calcium overload (TRPC channels), apoptosis (BAX/caspase 3/PARP), fibrosis (Smad3/TGF-β), hypoxia signaling (HIF-1α), and DNA damage (γ-H2AX).\n\nConversely, SS-31 increased antioxidant proteins (HO-1/NQO-1/GR/GPx), anti-fibrotic markers (Smad1/5, BMP-2), small vessel number, and alveolar sacs — demonstrating comprehensive protection of lung tissue architecture and function.","whyItMatters":"Pulmonary arterial hypertension has limited treatment options and carries a poor prognosis. SS-31 (also known as elamipretide/Bendavia) is a remarkable peptide that selectively targets the inner mitochondrial membrane, protecting cells from oxidative damage at its source. This study shows SS-31 improves virtually every aspect of PAH pathology — from blood pressure to fibrosis to DNA damage — suggesting that mitochondrial dysfunction is a central driver of PAH and that targeting it with this peptide addresses the root cause rather than just symptoms.","specificNumbers":"2 mg/day × 60 days · RVSBP significantly reduced · 8+ pathological pathways improved · Antioxidant proteins increased · Lung injury score improved · Muscularized vessels reduced","methodology":"Adult male C57BL mice were divided into three groups: sham-operated controls, TAC-induced PAH, and TAC+SS-31 (2 mg/day intraperitoneal for 60 days). Right ventricular systolic blood pressure was measured on day 60. Heart and lung tissues were analyzed for oxidative stress, inflammation, calcium overload, apoptosis, fibrosis, hypoxia, DNA damage, and endothelial function markers via histological and biochemical examination.","limitations":"This is a mouse model study using TAC-induced PAH, which may not fully replicate the complex pathophysiology of human pulmonary hypertension. Only one dose of SS-31 was tested, so the optimal therapeutic dose is unknown. The 60-day treatment period is relatively short for a chronic disease. The mechanisms were characterized descriptively (biomarker changes) without detailed pathway analysis to determine which effects are primary versus secondary to mitochondrial protection."},{"rthcId":"RPEP-03029","title":"pH-Triggered Release of Hydrophobic Molecules from Self-Assembling Hybrid Nanoscaffolds.","authors":"Lu, Lei; Unsworth, Larry D","year":2016,"journal":"Biomacromolecules, 17(4), 1425-36","doi":"10.1021/acs.biomac.6b00040","pmid":"26938197","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The hybrid nanoscaffold system composed of (RADA)4 peptide matrix and chitosan/carboxymethyl-β-cyclodextrin nanoparticles successfully encapsulated hydrophobic dexamethasone and exhibited pH-sensitive release. At physiological pH (~7), dexamethasone was released over more than 8 days with distinct kinetic phases, driven by chitosan deprotonation leading to nanoparticle dissociation.","whyItMatters":"This work addresses the challenge of delivering hydrophobic drugs using peptide-based scaffolds, which is important for improving therapies involving anti-inflammatory, anticancer, and antibacterial agents. Controlled, pH-triggered release enhances targeted treatment and reduces side effects.","specificNumbers":"","methodology":"The study developed a self-assembling hybrid nanoscaffold by incorporating chitosan/cyclodextrin nanoparticles loaded with dexamethasone into a (RADA)4 peptide hydrogel matrix. In vitro drug release experiments were conducted at different pH levels to observe release kinetics and mechanisms.","limitations":"The study was conducted in vitro, so in vivo behavior and biocompatibility remain to be tested. The evidence strength and study type were not specified, limiting assessment of robustness."},{"rthcId":"RPEP-03030","title":"The role of substance P in the maintenance of colonic hypermotility induced by repeated stress in rats.","authors":"Lu, Ping; Luo, Hesheng; Quan, Xiaojing; Fan, Han; Tang, Qincai; Yu, Guang; Chen, Wei; Xia, Hong","year":2016,"journal":"Neuropeptides, 56, 75-82","doi":"10.1016/j.npep.2016.01.006","pmid":"26851827","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Repeated water avoidance stress in rats elevates serum substance P levels and upregulates neurokinin-1 receptor expression in the colon, leading to increased colonic muscle contractility. The enhanced L-type calcium channel currents in smooth muscle cells contribute to this hypermotility, and selective NK1R antagonists can reverse the increased contractions.","whyItMatters":"Understanding how stress affects gut motility through substance P and its receptor helps identify new targets for treating stress-related gastrointestinal disorders like irritable bowel syndrome.","specificNumbers":"","methodology":"Male Wistar rats were subjected to 1 hour per day of water avoidance stress for up to 10 days. Serum substance P levels were measured by enzyme immunoassay. NK1 receptor expression was assessed using immunohistochemistry and Western blotting. Colonic muscle contractions were recorded in an organ bath system, and calcium channel currents in smooth muscle cells were measured using whole-cell patch-clamp technique.","limitations":"The study was conducted in rats, so results may not fully translate to humans. The exact signaling pathways downstream of calcium channel activation were not explored in detail."},{"rthcId":"RPEP-03031","title":"PFR peptide, one of the antimicrobial peptides identified from the derivatives of lactoferrin, induces necrosis in leukemia cells.","authors":"Lu, Yan; Zhang, Teng-Fei; Shi, Yue; Zhou, Han-Wei; Chen, Qi; Wei, Bu-Yun; Wang, Xi; Yang, Tian-Xin; Chinn, Y Eugene; Kang, Jian; Fu, Cai-Yun","year":2016,"journal":"Scientific reports, 6, 20823","doi":"10.1038/srep20823","pmid":"26860588","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"PFR peptide inhibits proliferation of MEL and HL-60 leukemia cells by inducing necrotic cell death characterized by membrane disruption, increased intracellular calcium, and LDH release, rather than apoptosis. It also causes G0/G1 cell cycle arrest and demonstrates antitumor activity and tolerability in vivo.","whyItMatters":"This study highlights the potential of antimicrobial peptides like PFR as novel leukemia treatments that kill cancer cells through necrosis, offering an alternative to apoptosis-based therapies.","specificNumbers":"","methodology":"The study evaluated the cytotoxic effects of PFR peptide on leukemia cell lines MEL and HL-60 using assays for cell death markers, membrane integrity, calcium levels, and cell cycle analysis. In vivo antitumor activity and tolerability were also assessed.","limitations":"The study does not specify the clinical relevance or long-term effects of PFR peptide treatment, and the exact in vivo models and sample sizes are not detailed."},{"rthcId":"RPEP-03032","title":"Substance P Promotes the Progression of Endometrial Adenocarcinoma.","authors":"Ma, Jing; Yuan, Shifa; Cheng, Jianxin; Kang, Shan; Zhao, Wenhong; Zhang, Jie","year":2016,"journal":"International journal of gynecological cancer : official journal of the International Gynecological Cancer Society, 26(5), 845-50","doi":"10.1097/IGC.0000000000000683","pmid":"27051050","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Both substance P (SP) and its receptor NK-1R were expressed at significantly higher levels in endometrial adenocarcinoma tissues and Ishikawa cancer cells compared to normal endometrium.\n\nSubstance P treatment significantly enhanced Ishikawa cell proliferation (measured by MTT assay) and invasion through matrigel barriers (transwell assay). Mechanistically, SP induced upregulation of MMP-9 (matrix metalloproteinase 9, which degrades extracellular matrix to enable invasion) and VEGF-C (vascular endothelial growth factor C, which promotes lymphangiogenesis and metastasis). All of these effects were blocked when an NK-1R antagonist was applied.","whyItMatters":"Endometrial cancer is the most common gynecological cancer in developed countries, with rising incidence linked to the obesity epidemic. Current treatments — surgery, radiation, hormonal therapy — have significant limitations for advanced disease. If substance P drives cancer progression through a druggable receptor (NK-1R), existing NK-1R antagonists (like aprepitant, already approved for chemotherapy-induced nausea) could potentially be repurposed as anti-cancer agents for endometrial carcinoma.","specificNumbers":"","methodology":"SP and NK-1R expression levels were measured in endometrial adenocarcinoma tissue samples and the Ishikawa endometrial cancer cell line using real-time quantitative PCR and Western blot analysis. Cell proliferation was assessed using MTT assays after SP treatment. Invasive capacity was evaluated using transwell matrigel invasion assays. MMP-9 and VEGF-C expression changes after SP exposure were quantified by PCR and Western blot. NK-1R antagonist was applied to test whether blocking the receptor inhibited SP's pro-cancer effects.","limitations":"Only one endometrial cancer cell line (Ishikawa) was used, which may not represent the diversity of endometrial cancers. No animal models or in vivo experiments were conducted to confirm the findings in living organisms. The number of human tissue samples compared is not specified in the abstract. The specific NK-1R antagonist used and its concentration are not detailed. The study does not assess whether blocking SP/NK-1R affects normal endometrial cells or would have side effects."},{"rthcId":"RPEP-03033","title":"Changes in the disposition of substance P in the rostral ventromedial medulla after inflammatory injury in the rat.","authors":"Maduka, U P; Hamity, M V; Walder, R Y; White, S R; Li, Y; Hammond, D L","year":2016,"journal":"Neuroscience, 317, 1-11","doi":"10.1016/j.neuroscience.2015.12.054","pmid":"26762802","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Peripheral inflammatory injury caused a significant increase in the density of substance P-immunoreactive processes in the RVM within hours and days after injury, without changing overall substance P protein or Tac1 transcript levels in the RVM. Substance P content increased in the PAG and cuneiform nuclei four days post-injury, indicating enhanced synthesis in neurons projecting to the RVM.","whyItMatters":"Understanding how substance P dynamics change in pain-related brain regions helps clarify mechanisms of inflammatory pain and could guide development of targeted pain therapies.","specificNumbers":"","methodology":"The study used enzyme immunoassay and RT-qPCR to measure substance P protein and Tac1 mRNA in rat brain tissue after inducing peripheral inflammation via intraplantar injection of complete Freund's adjuvant. Immunohistochemistry and mass spectrometry confirmed substance P localization and excluded confounding peptides.","limitations":"The study was conducted in rats, so results may not fully translate to humans; also, the evidence strength and study type were not specified, limiting assessment of robustness."},{"rthcId":"RPEP-03034","title":"New ligands of the ghrelin receptor based on the 1,2,4-triazole scaffold by introduction of a second chiral center.","authors":"Maingot, Mathieu; Blayo, Anne-Laure; Denoyelle, Séverine; M'Kadmi, Céline; Damian, Marjorie; Mary, Sophie; Gagne, Didier; Sanchez, Pierre; Aicher, Babette; Schmidt, Peter; Müller, Gilbert; Teifel, Michael; Günther, Eckhard; Marie, Jacky; Banères, Jean-Louis; Martinez, Jean; Fehrentz, Jean-Alain","year":2016,"journal":"Bioorganic & medicinal chemistry letters, 26(10), 2408-2412","doi":"10.1016/j.bmcl.2016.04.003","pmid":"27072910","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"By introducing a second chiral center to a previously described 1,2,4-triazole scaffold, the researchers expanded the chemical diversity of their ghrelin receptor ligand library and extended the molecule's 'C-terminal part' to mimic substance P analog inverse agonists.\n\nSeveral compounds achieved nanomolar binding affinities at the ghrelin receptor (GHS-R1a) with potent biological activities. One compound demonstrated partial inverse agonist behavior — meaning it not only blocked ghrelin from activating the receptor but actively reduced the receptor's constitutive (basal) signaling. This is pharmacologically significant because the ghrelin receptor has high constitutive activity, which contributes to baseline appetite drive.","whyItMatters":"The ghrelin receptor is one of the most attractive drug targets for obesity, but developing effective drugs has been challenging. Ghrelin receptor inverse agonists are particularly interesting because the receptor is constitutively active — it signals even without ghrelin binding, maintaining a baseline appetite drive. A drug that suppresses this basal signaling could reduce appetite more effectively than simply blocking ghrelin. Achieving this with a small molecule (rather than a peptide) would enable oral drug delivery, dramatically improving patient convenience and reducing cost.","specificNumbers":"","methodology":"Chemical synthesis of 1,2,4-triazole derivatives incorporating a second chiral center, inspired by the structure of substance P analogs known to act as ghrelin receptor inverse agonists. Binding affinity was determined by competitive radioligand displacement assays. Biological activity was assessed using functional assays measuring receptor activation (agonism), inhibition (antagonism), and inverse agonism (suppression of constitutive activity).","limitations":"The abstract describes only in vitro binding and functional data — no in vivo experiments were performed to assess effects on food intake, body weight, or metabolic parameters. Selectivity over other receptors was not detailed. The pharmacokinetic properties (oral bioavailability, half-life, brain penetration) that would determine clinical utility were not assessed. Only binding affinities and functional activities at the ghrelin receptor were reported; off-target effects are unknown."},{"rthcId":"RPEP-03035","title":"Effects of retinoic acid on growth hormone-releasing hormone receptor, growth hormone secretagogue receptor gene expression and growth hormone secretion in rat anterior pituitary cells.","authors":"Maliza, Rita; Fujiwara, Ken; Tsukada, Takehiro; Azuma, Morio; Kikuchi, Motoshi; Yashiro, Takashi","year":2016,"journal":"Endocrine journal, 63(6), 555-61","doi":"10.1507/endocrj.EJ16-0086","pmid":"27052215","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Retinoic acid (ATRA) upregulated gene expression of both GHRH receptor and ghrelin receptor (GHS-R) in rat pituitary cells, but did not change somatostatin receptor expression. This selectively enhanced the pituitary's responsiveness to the stimulatory peptides GHRH and ghrelin while leaving the inhibitory somatostatin pathway unchanged. ATRA amplified GHRH- and ghrelin-stimulated growth hormone release without affecting basal secretion. Effects were mediated through the RAR-RXR nuclear receptor complex.","whyItMatters":"This reveals a new layer of regulation for growth hormone release: vitamin A (retinoic acid) selectively tunes the pituitary's sensitivity to peptide hormones GHRH and ghrelin. Understanding this mechanism could inform approaches to growth disorders, aging-related GH decline, and conditions where GHRH/ghrelin signaling is impaired.","specificNumbers":"ATRA 10⁻⁶ M · 24h treatment · increased Ghrh-r and Ghs-r mRNA · Sst-r2 and Sst-r5 unchanged · enhanced GHRH- and ghrelin-stimulated GH release · basal GH unaffected","methodology":"Anterior pituitary cells isolated from male Wistar rats were cultured and treated with ATRA (10⁻⁶ M) for 24 hours. Receptor gene expression was measured by quantitative real-time PCR. Growth hormone release was assessed under basal and stimulated (GHRH, ghrelin) conditions. RAR-agonist (Am80) and RXR-agonist (PA024) were tested to confirm receptor pathway involvement.","limitations":"In vitro study using isolated rat pituitary cells — the in vivo regulatory context (hypothalamic input, feedback loops) is absent. Only one concentration of ATRA and one time point were tested. Human pituitary cells may respond differently. The functional significance of the receptor upregulation for whole-organism GH physiology was not assessed."},{"rthcId":"RPEP-03036","title":"New insights into the bioactivity of peptides from probiotics.","authors":"Mandal, Santi M; Pati, Bikas R; Chakraborty, Ranadhir; Franco, Octavio L","year":2016,"journal":"Frontiers in bioscience (Elite edition), 8(3), 450-9","doi":null,"pmid":"27100351","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03037","title":"Antimicrobial peptides and wound healing: biological and therapeutic considerations.","authors":"Mangoni, Maria Luisa; McDermott, Alison M; Zasloff, Michael","year":2016,"journal":"Experimental dermatology, 25(3), 167-73","doi":"10.1111/exd.12929","pmid":"26738772","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Antimicrobial peptides serve dual roles as both defenders against microbial infections and as endogenous mediators that promote wound healing. They have promising therapeutic potential for treating non-life-threatening skin and epithelial injuries.","whyItMatters":"Understanding how AMPs contribute to wound repair could lead to new treatments that enhance healing and reduce infections, benefiting patients with skin injuries.","specificNumbers":"","methodology":"This article is a brief review summarizing existing evidence on the biological functions of antimicrobial peptides in wound healing and their therapeutic applications.","limitations":"As a review, the study does not present new experimental data and the strength of evidence varies across cited studies."},{"rthcId":"RPEP-03038","title":"Use of ghrelin in cachexia syndrome: a systematic review of clinical trials.","authors":"Mansson, Jéssica V; Alves, Fernanda D; Biolo, Andréia; Souza, Gabriela C","year":2016,"journal":"Nutrition reviews, 74(11), 659-669","doi":null,"pmid":"27753623","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03039","title":"The role of antimicrobial peptides in chronic inflammatory skin diseases.","authors":"Marcinkiewicz, Małgorzata; Majewski, Sławomir","year":2016,"journal":"Postepy dermatologii i alergologii, 33(1), 6-12","doi":"10.5114/pdia.2015.48066","pmid":"26985172","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review highlights that antimicrobial peptides are dysregulated in chronic inflammatory skin diseases, with overproduction in psoriasis and rosacea lesions and reduced levels in atopic dermatitis, indicating their significant role in disease pathogenesis and host immunity.","whyItMatters":"Understanding how AMPs contribute to skin diseases can help develop new treatments targeting these peptides to better manage inflammation and infection in chronic skin conditions.","specificNumbers":"","methodology":"This article is a literature review summarizing current knowledge on the biology and clinical relevance of antimicrobial peptides in inflammatory skin diseases based on existing research.","limitations":"As a review, it does not present new experimental data and the evidence strength and study types of cited works vary, limiting definitive conclusions."},{"rthcId":"RPEP-03040","title":"Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes.","authors":"Marso, Steven P; Daniels, Gilbert H; Brown-Frandsen, Kirstine; Kristensen, Peter; Mann, Johannes F E; Nauck, Michael A; Nissen, Steven E; Pocock, Stuart; Poulter, Neil R; Ravn, Lasse S; Steinberg, William M; Stockner, Mette; Zinman, Bernard; Bergenstal, Richard M; Buse, John B","year":2016,"journal":"The New England journal of medicine, 375(4), 311-22","doi":"10.1056/NEJMoa1603827","pmid":"27295427","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03041","title":"Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes.","authors":"Marso, Steven P; Bain, Stephen C; Consoli, Agostino; Eliaschewitz, Freddy G; Jódar, Esteban; Leiter, Lawrence A; Lingvay, Ildiko; Rosenstock, Julio; Seufert, Jochen; Warren, Mark L; Woo, Vincent; Hansen, Oluf; Holst, Anders G; Pettersson, Jonas; Vilsbøll, Tina","year":2016,"journal":"The New England journal of medicine, 375(19), 1834-1844","doi":null,"pmid":"27633186","tags":["glp-1","cardiovascular"],"studyType":"rct","evidenceStrength":"strong","keyFinding":"In the landmark SUSTAIN-6 trial, weekly semaglutide reduced the rate of major cardiovascular events (cardiovascular death, nonfatal heart attack, or nonfatal stroke) by 26% compared to placebo in patients with type 2 diabetes at high cardiovascular risk (hazard ratio 0.74; 95% CI 0.58–0.95; P<0.001 for noninferiority). The composite primary endpoint occurred in 6.6% of semaglutide patients versus 8.9% of placebo patients over 104 weeks.\n\nNonfatal stroke was reduced by 39% (HR 0.61; P=0.04) and nonfatal heart attack by 26% (HR 0.74; P=0.12, not statistically significant). Rates of new or worsening kidney disease were also lower with semaglutide. However, the trial flagged an unexpected safety signal: retinopathy complications were significantly higher with semaglutide (HR 1.76; P=0.02), a finding that required further investigation.","whyItMatters":"SUSTAIN-6 was a watershed moment for GLP-1 drugs. It was designed simply to prove semaglutide wasn't harmful to the heart (as required by FDA), but instead showed it was actively protective — reducing heart attacks and strokes by 26% overall. This transformed semaglutide from a diabetes drug into a cardiovascular medication and paved the way for its massive commercial success. The trial also revealed the retinopathy signal that would become an important monitoring point for clinicians prescribing semaglutide.","specificNumbers":"","methodology":"Double-blind, randomized, placebo-controlled trial (SUSTAIN-6). 3,297 patients with type 2 diabetes on standard care were randomized to receive once-weekly semaglutide (0.5 mg or 1.0 mg) or placebo for 104 weeks. 83% of patients had established cardiovascular disease, chronic kidney disease, or both. The primary composite endpoint was the first occurrence of cardiovascular death, nonfatal MI, or nonfatal stroke.","limitations":"The trial was designed as a noninferiority study, not a superiority study — it was powered to show semaglutide wasn't worse than placebo, not necessarily that it was better. The significant increase in retinopathy complications raised safety concerns. Cardiovascular death rates were not significantly different between groups. The study population was high-risk diabetes patients, so results may not generalize to all semaglutide users (e.g., those taking it purely for weight loss without diabetes)."},{"rthcId":"RPEP-03042","title":"Ghrelin acts as energy status sensor of male reproduction by modulating Sertoli cells glycolytic metabolism and mitochondrial bioenergetics.","authors":"Martins, A D; Sá, R; Monteiro, M P; Barros, A; Sousa, M; Carvalho, R A; Silva, B M; Oliveira, P F; Alves, M G","year":2016,"journal":"Molecular and cellular endocrinology, 434, 199-209","doi":"10.1016/j.mce.2016.07.008","pmid":"27392494","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Ghrelin modulates human Sertoli cells' glycolytic metabolism and mitochondrial bioenergetics in a dose-dependent manner, with higher ghrelin levels (as seen in undernourished individuals) causing more pronounced decreases in pyruvate consumption, mitochondrial complex III expression, and production of alanine and acetate. This indicates ghrelin acts as an energy status sensor regulating the metabolic support for spermatogenesis.","whyItMatters":"Understanding how ghrelin regulates Sertoli cell metabolism provides insight into the link between nutrition, energy status, and male reproductive health. This knowledge could inform strategies to improve fertility in men affected by nutritional imbalances.","specificNumbers":"","methodology":"Human Sertoli cells were exposed in vitro to increasing concentrations of ghrelin (20, 100, and 500 pM) reflecting plasma levels in obese, normal weight, and severely undernourished men. Metabolite production and consumption, protein levels of glycolytic enzymes and mitochondrial complexes, lactate dehydrogenase activity, and mitochondrial membrane potential were measured to assess metabolic changes.","limitations":"The study was conducted in vitro using isolated human Sertoli cells, which may not fully replicate the complex in vivo environment of the testes. The exact impact on spermatogenesis and fertility in living organisms remains to be confirmed."},{"rthcId":"RPEP-03043","title":"Comparative proteomic analysis of growth hormone secretagogue A233 treatment of murine macrophage cells J774A.2 indicates it has a role in antiviral innate response.","authors":"Martínez, Rebeca; de Villavicencio-Díaz, Teresa Núñez; Sánchez, Aniel; Ramos, Yassel; Ferro, Jesús Noda; González, Lázaro Gil; Méndez, Milagros; Rodríguez, Elsa; Marcos, Ernesto; Sánchez, Belinda; Masforrol, Yordanka; Garay, Hilda; Albericio, Fernando; Hermida, Lisset; González, Luis Javier; Vonasek, Eva; Estrada, Mario P; Besada, Vladimir","year":2016,"journal":"Biochemistry and biophysics reports, 5, 379-387","doi":"10.1016/j.bbrep.2016.01.008","pmid":"28955845","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A233 peptide treatment activates reactive oxygen species (ROS)-dependent cytotoxic functions in murine macrophage cells and enhances expression of antiviral protein complexes such as MAVS. This leads to increased superoxide anion production, elevated IFN-γ levels in immune cells, and a reduction in viral load in a dengue virus mouse infection model.","whyItMatters":"Understanding how A233 modulates innate immunity can help develop new peptide-based therapies to enhance antiviral defenses, potentially benefiting treatment of viral infections like dengue.","specificNumbers":"","methodology":"The study used comparative proteomic analysis of J774A.2 murine macrophage cells treated with A233 peptide for 6 and 12 hours. Functional protein changes were analyzed, and effects on reactive oxygen species production, IFN-γ levels, and viral load in a dengue virus mouse model were measured.","limitations":"The study was conducted primarily in vitro and in a mouse model, so results may not fully translate to humans. The exact mechanisms and clinical relevance require further investigation."},{"rthcId":"RPEP-03044","title":"Efficacy and Safety of Liraglutide Added to Insulin Treatment in Type 1 Diabetes: The ADJUNCT ONE Treat-To-Target Randomized Trial.","authors":"Mathieu, Chantal; Zinman, Bernard; Hemmingsson, Joanna Uddén; Woo, Vincent; Colman, Peter; Christiansen, Erik; Linder, Martin; Bode, Bruce","year":2016,"journal":"Diabetes care, 39(10), 1702-10","doi":"10.2337/dc16-0691","pmid":"27506222","tags":["glp-1-agonists","diabetes"],"studyType":"rct","evidenceStrength":"high","keyFinding":"Adding liraglutide to insulin therapy in type 1 diabetes modestly improved blood sugar control (HbA1c reduced 0.20% more than placebo at the 1.8 mg dose), reduced total insulin requirements by 8%, and produced significant weight loss (up to 4.9 kg at 1.8 mg vs placebo). However, these benefits came with increased rates of symptomatic hypoglycemia across all doses and a significantly higher rate of hyperglycemia with ketosis at the 1.8 mg dose (2.22× higher than placebo).\n\nThe safety trade-offs — more low blood sugar episodes and more ketosis events — were judged to limit the clinical usefulness of liraglutide in type 1 diabetes.","whyItMatters":"This is the largest trial (ADJUNCT ONE) testing whether a GLP-1 agonist could benefit people with type 1 diabetes when added to insulin. While the metabolic benefits were real — better blood sugar, less insulin needed, weight loss — the increased risk of hypoglycemia and ketosis meant the drug wasn't safe enough for routine use in this population. This study is a key reason GLP-1 agonists remain off-label for type 1 diabetes.","specificNumbers":"n=1,398 · 52 weeks · HbA1c ETD: −0.20% (1.8 mg) · Insulin reduction: 8% (1.8 mg) · Weight loss: −4.9 kg (1.8 mg), −3.6 kg (1.2 mg), −2.2 kg (0.6 mg) · Hypoglycemia rate ratio: 1.31 (1.8 mg) · Ketosis rate ratio: 2.22 (1.8 mg only)","methodology":"52-week, double-blind, randomized, placebo-controlled, treat-to-target trial. 1,398 adults with type 1 diabetes were randomized 3:1 to receive liraglutide (1.8, 1.2, or 0.6 mg) or placebo once daily via subcutaneous injection, added to their existing insulin regimen. Insulin doses were adjusted to maintain target blood glucose throughout the trial.","limitations":"The treat-to-target insulin adjustment protocol may have contributed to hypoglycemia by encouraging aggressive insulin dosing alongside liraglutide. The study population had mean baseline HbA1c of 8.2%, which may not represent all type 1 diabetes patients. The trial wasn't designed to identify which subgroups might benefit safely."},{"rthcId":"RPEP-03045","title":"Bradykinin Induces TRPV1 Exocytotic Recruitment in Peptidergic Nociceptors.","authors":"Mathivanan, Sakthikumar; Devesa, Isabel; Changeux, Jean-Pierre; Ferrer-Montiel, Antonio","year":2016,"journal":"Frontiers in pharmacology, 7, 178","doi":"10.3389/fphar.2016.00178","pmid":"27445816","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Bradykinin sensitizes TRPV1 channels in peptidergic nociceptors primarily via the bradykinin receptor 2 pathway, involving Ca(2+)-dependent exocytotic recruitment of TRPV1 channels trafficked by αCGRP-loaded large dense core vesicles. Silencing αCGRP expression significantly reduces this sensitization, highlighting its key role.","whyItMatters":"Understanding how bradykinin increases pain receptor sensitivity helps identify new targets for pain relief, especially by blocking the exocytosis process that increases pain channel presence on nerve cells.","specificNumbers":"","methodology":"The study used molecular and cellular techniques to assess TRPV1 sensitization in peptidergic nociceptors, including inhibition of Ca(2+)-dependent exocytosis and gene silencing of αCGRP and substance P to determine their roles in bradykinin-induced effects.","limitations":"The study type and evidence strength are not specified, and the findings are primarily from cellular models which may not fully represent complex in vivo pain mechanisms."},{"rthcId":"RPEP-03046","title":"Progress in Small Molecule and Biologic Therapeutics Targeting Ghrelin Signaling.","authors":"McGovern, Kayleigh R; Darling, Joseph E; Hougland, James L","year":2016,"journal":"Mini reviews in medicinal chemistry, 16(6), 465-80","doi":null,"pmid":"26202202","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Therapeutic strategies targeting ghrelin signaling include agonists and antagonists of the GHS-R1a receptor, as well as agents that reduce circulating ghrelin or inhibit ghrelin O-acyltransferase, with varying effectiveness demonstrated in preclinical and clinical studies.","whyItMatters":"Understanding and manipulating ghrelin signaling could lead to new treatments for metabolic and neurological diseases linked to appetite and energy balance, addressing major public health issues.","specificNumbers":"","methodology":"This article is a review summarizing recent research on small molecule and biologic agents targeting ghrelin signaling pathways, analyzing their mechanisms, therapeutic potential, and challenges.","limitations":"The review does not provide new experimental data and the evidence strength and clinical efficacy of many agents remain uncertain due to limited human trials."},{"rthcId":"RPEP-03047","title":"Rosacea: The Blessing of the Celts - An Approach to Pathogenesis Through Translational Research.","authors":"Melnik, Bodo C","year":2016,"journal":"Acta dermato-venereologica, 96(2), 147-56","doi":"10.2340/00015555-2220","pmid":"26304030","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Rosacea is associated with upregulated endoplasmic reticulum (ER) stress and sphingosine-1-phosphate (S1P) signaling, which compensates for low vitamin D-dependent cathelicidin antimicrobial peptide (CAMP) expression during low UV exposure. This adaptation may have evolved in Celts to maintain antimicrobial defense in winter.","whyItMatters":"Understanding rosacea as an evolutionary mechanism to sustain antimicrobial peptide levels could shift perspectives on its treatment and highlight the importance of CAMP regulation in skin immunity.","specificNumbers":"","methodology":"The study is a translational research review that integrates molecular biology findings on CAMP gene regulation, ER stress responses, and clinical observations of rosacea triggers to propose a pathogenesis model.","limitations":"The study is largely theoretical and based on molecular and clinical correlations without direct experimental validation of the proposed mutation or pathway in rosacea patients."},{"rthcId":"RPEP-03048","title":"Evidence for the existence of nociceptors in rat thoracolumbar fascia.","authors":"Mense, Siegfried; Hoheisel, Ulrich","year":2016,"journal":"Journal of bodywork and movement therapies, 20(3), 623-8","doi":"10.1016/j.jbmt.2016.01.006","pmid":"27634088","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Nociceptive fibers positive for CGRP, substance P, and TRPV1 were found in all three layers of the rat thoracolumbar fascia (TLF). When inflammation was induced with complete Freund's adjuvant, CGRP- and SP-positive fiber density significantly increased in the inner layer (covering the multifidus muscle) and outer layer, but not the thick middle layer. Electrical stimulation of dorsal roots caused plasma extravasation in the TLF — direct functional evidence that fascia nociceptors can drive neurogenic inflammation.","whyItMatters":"Non-specific low back pain is one of the most common and costly health conditions worldwide, yet its source is often unclear. This study provides concrete evidence that fascia contains pain-sensing nerve fibers expressing key neuropeptides, and that these fibers proliferate during inflammation. This points to fascia as an underrecognized pain generator and potential therapeutic target.","specificNumbers":"","methodology":"Histological study in Sprague-Dawley rats. Immunohistochemistry using antibodies against CGRP, substance P, and TRPV1 identified nociceptive fibers across the three layers of the thoracolumbar fascia. Chronic inflammation was induced by injecting complete Freund's adjuvant. Neurogenic inflammation was tested by electrically stimulating dorsal roots and observing plasma extravasation in the fascia.","limitations":"This is a rat study, and the fascia anatomy and innervation may differ from humans. Specific sample sizes and statistical values were not detailed in the abstract. The inflammation model (complete Freund's adjuvant) creates a severe inflammatory state that may not perfectly mimic clinical conditions like non-specific low back pain. The study demonstrates nociceptor presence but doesn't directly prove they cause pain perception."},{"rthcId":"RPEP-03049","title":"Targeting EphA2-Sam and Its Interactome: Design and Evaluation of Helical Peptides Enriched in Charged Residues.","authors":"Mercurio, Flavia A; Marasco, Daniela; Di Natale, Concetta; Pirone, Luciano; Costantini, Susan; Pedone, Emilia M; Leone, Marilisa","year":2016,"journal":"Chembiochem : a European journal of chemical biology, 17(22), 2179-2188","doi":"10.1002/cbic.201600413","pmid":"27763725","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Two helical peptides enriched in charged residues were identified that bind specifically to the first Sam domain of Odin, a protein interacting with EphA2-Sam. These peptides represent early candidates for disrupting EphA2-Sam heterotypic interactions, which are primarily electrostatic in nature.","whyItMatters":"Targeting the EphA2 receptor's Sam domain with peptides could offer a novel approach to promote receptor degradation and inhibit cancer progression. Understanding and disrupting protein interactions at this site may lead to new therapeutic strategies.","specificNumbers":"","methodology":"The study involved designing multiple peptide sequences with high helical propensity and charged residues. Their structures were analyzed using nuclear magnetic resonance (NMR), circular dichroism (CD), and molecular dynamics simulations. Binding interactions were assessed through NMR, surface plasmon resonance (SPR), and microscale thermophoresis (MST).","limitations":"The study is preliminary and focuses on peptide binding in vitro without demonstrating functional effects in cells or animal models. The exact therapeutic potential and specificity of these peptides remain to be validated."},{"rthcId":"RPEP-03050","title":"Effect of Abaloparatide vs Placebo on New Vertebral Fractures in Postmenopausal Women With Osteoporosis: A Randomized Clinical Trial.","authors":"Miller, Paul D; Hattersley, Gary; Riis, Bente Juel; Williams, Gregory C; Lau, Edith; Russo, Luis Augusto; Alexandersen, Peter; Zerbini, Cristiano A F; Hu, Ming-yi; Harris, Alan G; Fitzpatrick, Lorraine A; Cosman, Felicia; Christiansen, Claus","year":2016,"journal":"JAMA, 316(7), 722-33","doi":"10.1001/jama.2016.11136","pmid":"27533157","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03051","title":"Role of substance P in the cardiovascular system.","authors":"Mistrova, Eliska; Kruzliak, Peter; Chottova Dvorakova, Magdalena","year":2016,"journal":"Neuropeptides, 58, 41-51","doi":"10.1016/j.npep.2015.12.005","pmid":"26706184","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Substance P, acting primarily through neurokinin receptor 1, is involved in cardiovascular regulation including heart rate, blood pressure, vessel stretching, ischemia-reperfusion injury, and stress responses. Neurokinin receptor 1 antagonists have therapeutic potential in cardiovascular and other pathological conditions.","whyItMatters":"Understanding substance P's cardiovascular roles may help develop new treatments for heart diseases and vascular conditions, as well as improve management of inflammation and pain.","specificNumbers":"","methodology":"This article is a review summarizing existing research on the structure, function, and cardiovascular roles of substance P and its receptor system.","limitations":"The article is a review and does not present new experimental data; the strength of evidence for some roles of substance P in cardiovascular function is not detailed."},{"rthcId":"RPEP-03052","title":"Early effects of Roux-en-Y gastric bypass on peptides and hormones involved in the control of energy balance.","authors":"Molin Netto, Bárbara Dal; Earthman, Carrie P; Cravo Bettini, Solange; Grotti Clemente, Ana Paula; Landi Masquio, Deborah Cristina; Farias, Gisele; Boritza, Katia; da Silva, Larissa Gabrielle; von der Heyde, Maria Emilia; Dâmaso, Ana Raimunda","year":2016,"journal":"European journal of gastroenterology & hepatology, 28(9), 1050-5","doi":"10.1097/MEG.0000000000000665","pmid":"27203601","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 39 individuals with extreme obesity, 6 months after Roux-en-Y gastric bypass:\n\n- BMI decreased from 44.3 ± 6.4 to 31.7 ± 5.7 kg/m² (P < 0.001)\n- Percentage of excess weight lost: 63.2 ± 25.0%\n- Leptin and glucose levels decreased significantly (P < 0.001)\n- Significant positive correlation between PYY and α-MSH after surgery (r = 0.35, P = 0.004)\n- PYY correlated negatively with BMI (r = -0.34, P = 0.002)\n- Supports the PYY-to-POMC signal as a mechanism for appetite regulation post-RYGB","whyItMatters":"Understanding why gastric bypass works so well for weight loss — better than any drug — can help develop new medications. This study reveals a gut-brain peptide connection (PYY → α-MSH/POMC) that may be a key mechanism. If this pathway can be pharmacologically activated without surgery, it could lead to more effective obesity treatments.","specificNumbers":"","methodology":"Prospective observational study of 39 individuals with extreme obesity (37 women, 2 men) undergoing Roux-en-Y gastric bypass. Anthropometric measurements and biochemical markers (including PYY, α-MSH, leptin, glucose) were collected before surgery and 6 months post-RYGB. Correlations between hormone levels and BMI changes were analyzed.","limitations":"Small sample size (39 patients) with predominantly female participants (37/39), limiting generalizability to men. The observational design cannot establish causation. PYY and α-MSH were measured at only two time points. The study did not measure GLP-1 or other gut peptides that likely also contribute to post-surgical appetite suppression. Six-month follow-up may not reflect long-term hormonal changes."},{"rthcId":"RPEP-03053","title":"Mediators of Chronic Pruritus in Atopic Dermatitis: Getting the Itch Out?","authors":"Mollanazar, Nicholas K; Smith, Peter K; Yosipovitch, Gil","year":2016,"journal":"Clinical reviews in allergy & immunology, 51(3), 263-292","doi":null,"pmid":"25931325","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Chronic pruritus in atopic dermatitis results from a multifaceted interaction involving epidermal barrier dysfunction, immune system activation, and neural sensitization. Multiple receptors and mediators such as TRPA1, TRPV1, GRPR, histamine, cytokines (IL-4, IL-13, IL-31), and neuropeptides contribute to itch signaling. Emerging therapies like dupilumab target these pathways to provide more effective itch relief.","whyItMatters":"Understanding the complex causes of chronic itch can lead to better targeted treatments, improving quality of life for millions with atopic dermatitis and other itchy skin conditions.","specificNumbers":"","methodology":"This article is a comprehensive literature review summarizing current knowledge on the mediators of chronic itch in atopic dermatitis and discussing various therapeutic options based on recent research findings.","limitations":"As a review, it summarizes existing studies without new experimental data; the exact mechanisms and optimal treatments for chronic itch remain incompletely understood."},{"rthcId":"RPEP-03054","title":"Development of novel ligands for peptide GPCRs.","authors":"Moran, Brian M; McKillop, Aine M; O'Harte, Finbarr Pm","year":2016,"journal":"Current opinion in pharmacology, 31, 57-62","doi":"10.1016/j.coph.2016.08.009","pmid":"27607913","tags":["glp-1","gip","gpcr"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"This review maps out the landscape of peptide receptors on pancreatic beta cells that can be targeted for diabetes treatment. Beyond the well-known GLP-1 receptor, it covers GIP, glucagon, somatostatin, pancreatic polypeptide, CCK, PYY, oxyntomodulin, and ghrelin receptors — all G-protein coupled receptors (GPCRs) that regulate insulin secretion and metabolism.\n\nCritically, the review highlights the emerging strategy of dual and triple agonist peptides that activate two or more of these receptors simultaneously. It also covers fatty acid GPCRs (GPR40, GPR41, GPR43, GPR84, GPR119, GPR120) that regulate peptide hormone secretion and represent additional drug targets.","whyItMatters":"This 2016 review was remarkably prescient — the dual and triple agonist approach it described would go on to produce tirzepatide (GLP-1/GIP dual agonist, approved 2022) and retatrutide (GLP-1/GIP/glucagon triple agonist, in Phase 3 trials). Understanding the full map of peptide GPCRs on beta cells explains why multi-targeting approaches are more effective than single-receptor drugs for metabolic disease.","specificNumbers":"9+ peptide GPCRs on beta cells · 6 fatty acid GPCRs · Dual and triple agonist approaches · GLP-1, GIP, glucagon, somatostatin, PP, CCK, PYY, OXM, ghrelin receptors","methodology":"Narrative review of the current state of peptide GPCR drug development for type 2 diabetes, covering receptor biology, existing agonists, and emerging multi-agonist peptide strategies. Includes both preclinical and clinical evidence.","limitations":"Published in 2016, so it predates the clinical validation of many concepts it describes (e.g., tirzepatide's Phase 3 success). As a narrative review, it summarizes rather than systematically evaluates the evidence. Some receptor targets discussed remain preclinical."},{"rthcId":"RPEP-03055","title":"Bombesin related peptides/receptors and their promising therapeutic roles in cancer imaging, targeting and treatment.","authors":"Moreno, Paola; Ramos-Álvarez, Irene; Moody, Terry W; Jensen, Robert T","year":2016,"journal":"Expert opinion on therapeutic targets, 20(9), 1055-73","doi":"10.1517/14728222.2016.1164694","pmid":"26981612","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03056","title":"Inhibition of Candida albicans Biofilm Formation by the Synthetic Lactoferricin Derived Peptide hLF1-11.","authors":"Morici, Paola; Fais, Roberta; Rizzato, Cosmeri; Tavanti, Arianna; Lupetti, Antonella","year":2016,"journal":"PloS one, 11(11), e0167470","doi":"10.1371/journal.pone.0167470","pmid":"27902776","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"hLF1-11 inhibited biofilm formation by Candida albicans clinical isolates in a dose-dependent manner, regardless of their fluconazole resistance. It reduced biofilm cellular density, metabolic activity, and hyphal morphogenesis by downregulating genes in the Ras1-cAMP-Efg1 signaling pathway, with exogenous cAMP able to restore morphogenesis.","whyItMatters":"Biofilms protect Candida albicans from antifungal drugs, making infections difficult to treat. Finding agents like hLF1-11 that inhibit biofilm formation could improve prevention and treatment of fungal infections.","specificNumbers":"","methodology":"The study evaluated the in vitro antibiofilm activity of synthetic peptide hLF1-11 against clinical Candida albicans isolates with varying fluconazole susceptibility. Biofilm density, metabolic activity, and cell viability were measured, and gene expression related to biofilm formation was analyzed by qRT-PCR. Microscopy assessed morphological changes, and exogenous cAMP was used to test pathway involvement.","limitations":"The study was conducted in vitro, so effects in living organisms remain to be confirmed. The exact clinical efficacy and safety of hLF1-11 require further investigation."},{"rthcId":"RPEP-03057","title":"Targeting cardiac natriuretic peptides in the therapy of diabetes and obesity.","authors":"Moro, Cedric","year":2016,"journal":"Expert opinion on therapeutic targets, 20(12), 1445-1452","doi":null,"pmid":"27786597","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review synthesizes evidence that natriuretic peptide (NP) system deficiency is both associated with and potentially causal of obesity and type 2 diabetes:\n\n- Epidemiological studies show low NP levels predict future T2D risk\n- NPs signal through NPRA/cGMP and have direct metabolic effects in fat tissue, muscle, liver, and pancreas\n- NPs promote fat oxidation (fat burning), browning of white fat, and insulin secretion\n- Obese individuals typically have paradoxically low NP levels, which may perpetuate metabolic dysfunction\n- Two degradation pathways — the clearance receptor NPRC and neutral endopeptidases (NEP) — could be targeted to raise circulating NP levels\n- Recombinant ANP and BNP already exist as treatments for heart failure and could potentially be repurposed","whyItMatters":"While GLP-1 drugs dominate the obesity drug conversation, natriuretic peptides represent a completely different and complementary approach. These cardiac hormones act on fat tissue, muscle, and the pancreas through pathways distinct from incretins. If NP-boosting strategies can safely improve metabolic health, they could be used alongside or instead of GLP-1 drugs, particularly in patients with both heart failure and obesity — where NP deficiency may contribute to both conditions.","specificNumbers":"","methodology":"This is a narrative review examining epidemiological, clinical, and preclinical evidence on the natriuretic peptide system's role in metabolism. The author reviews molecular mechanisms of NP action in metabolic target tissues, the epidemiological association between NP deficiency and cardiometabolic risk, and potential therapeutic strategies for targeting the NP pathway.","limitations":"The review relies heavily on observational associations and preclinical data. While low NP levels correlate with metabolic risk, causation is difficult to establish definitively. Recombinant NPs require intravenous infusion and have potent blood pressure-lowering effects that may limit their use as metabolic drugs. The specificity of targeting NP degradation pathways (NPRC, NEP) for metabolic versus cardiovascular effects is unclear. No clinical trials specifically testing NP-based approaches for obesity or T2D are described."},{"rthcId":"RPEP-03058","title":"Emerging therapy in arthritis: Modulation of markers of the inflammatory process.","authors":"Mortarino, P A; Goy, D P; Abramson, D B; Cabello, J; Bumaguin, G E; Vitelli, E J; Toledo, J; Sarrio, L; Pezzotto, S M; Mardegan Issa, J P; Cointry, G R; Feldman, S","year":2016,"journal":"Microscopy research and technique, 79(2), 89-97","doi":"10.1002/jemt.22609","pmid":"26748745","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Simultaneous oral treatment with hydrolyzed collagen peptides and vitamin D3 significantly reduced proinflammatory cytokine levels and improved synovial tissue health in an antigen-induced arthritis rabbit model, compared to no treatment or either treatment alone.","whyItMatters":"This research highlights a potential new combination therapy that could enhance oral tolerance and immune regulation in autoimmune arthritis, offering a promising alternative to current treatments.","specificNumbers":"","methodology":"The study used an experimental antigen-induced arthritis model in New Zealand rabbits, treating groups with hydrolyzed collagen peptides, vitamin D3, both combined, or no treatment. Clinical observations, cytokine measurements, and anatomical-pathological analyses of synovial tissue were performed to assess inflammation and tissue changes.","limitations":"The study was conducted in rabbits, so results may not directly translate to humans; also, the study type and evidence strength were not clearly defined."},{"rthcId":"RPEP-03059","title":"Incorporation of liposomes containing squid tunic ACE-inhibitory peptides into fish gelatin.","authors":"Mosquera, Mauricio; Giménez, Begoña; Montero, Pilar; Gómez-Guillén, Maria Carmen","year":2016,"journal":"Journal of the science of food and agriculture, 96(3), 769-76","doi":"10.1002/jsfa.7145","pmid":"25704896","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Peptides with strong ACE-inhibitory activity (IC50 = 0.096 g/L) from squid tunics were successfully encapsulated in phosphatidylcholine nanoliposomes with 53% efficiency at an optimal concentration of 1.75 g/L. The liposomes remained stable and maintained their negative zeta potential (~-59 mV) and size (~70 nm) over one week at 4 °C and pH 3-7. Incorporation into fish gelatin did not affect gel properties, and the ACE-inhibitory activity was preserved.","whyItMatters":"This study demonstrates a method to protect bioactive peptides during food processing and storage, enhancing their potential as functional ingredients for managing blood pressure through diet.","specificNumbers":"","methodology":"Peptides under 1 kDa were isolated from hydrolyzed squid tunics and encapsulated in phosphatidylcholine nanoliposomes at varying concentrations. Liposome stability, size, and zeta potential were measured over time. The peptide-loaded liposomes were then incorporated into fish gelatin gels, and rheological and thermal properties were assessed alongside ACE-inhibitory activity.","limitations":"The study does not report in vivo efficacy or long-term stability beyond one week, and the impact on human health outcomes remains to be tested."},{"rthcId":"RPEP-03060","title":"The levels of blood mercury and inflammatory-related neuropeptides in the serum are correlated in children with autism spectrum disorder.","authors":"Mostafa, Gehan Ahmed; Bjørklund, Geir; Urbina, Mauricio A; Al-Ayadhi, Laila Yousef","year":2016,"journal":"Metabolic brain disease, 31(3), 593-9","doi":"10.1007/s11011-015-9784-8","pmid":"26738726","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Children with ASD showed significantly elevated serum neurokinin A and blood mercury levels compared to healthy controls, with a positive correlation between neurokinin A and mercury levels in moderate to severe ASD cases.","whyItMatters":"Understanding the link between mercury exposure and neuroinflammation in ASD could help identify environmental factors contributing to autism and guide new treatment approaches targeting inflammation.","specificNumbers":"","methodology":"The study measured serum neurokinin A and blood mercury levels in 84 children with ASD and 84 matched healthy controls aged 3 to 10 years, analyzing correlations with autism severity using the Childhood Autism Rating Scale.","limitations":"The study design and evidence strength were not specified, limiting conclusions about causality; also, the sample size, while moderate, may not represent all ASD populations."},{"rthcId":"RPEP-03061","title":"Oxytocin for Male Subjects with Autism Spectrum Disorder and Comorbid Intellectual Disabilities: A Randomized Pilot Study.","authors":"Munesue, Toshio; Nakamura, Hiroyuki; Kikuchi, Mitsuru; Miura, Yui; Takeuchi, Noriyuki; Anme, Tokie; Nanba, Eiji; Adachi, Kaori; Tsubouchi, Kiyotaka; Sai, Yoshimichi; Miyamoto, Ken-Ichi; Horike, Shin-Ichi; Yokoyama, Shigeru; Nakatani, Hideo; Niida, Yo; Kosaka, Hirotaka; Minabe, Yoshio; Higashida, Haruhiro","year":2016,"journal":"Frontiers in psychiatry, 7, 2","doi":"10.3389/fpsyt.2016.00002","pmid":"26834651","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In this randomized, double-blind, placebo-controlled crossover pilot study, 29 males aged 15–40 with ASD and intellectual disabilities received intranasal oxytocin (16 IU/day) or placebo for 8 weeks each. No serious adverse events occurred except one seizure in one participant — an important safety finding given that this population has elevated seizure risk.\n\nPrimary outcome (Childhood Autism Rating Scale) and secondary standard scale measures showed no significant difference between oxytocin and placebo. However, exploratory analysis revealed significantly more frequent social interactions during play sessions and daily life in the initial half of the oxytocin-first arm. Plasma oxytocin concentrations significantly correlated with irritability subscale scores on the Aberrant Behavior Checklist, suggesting a biological relationship between oxytocin levels and behavioral symptoms.","whyItMatters":"People with autism and intellectual disabilities represent the most underserved population in autism research — they're typically excluded from clinical trials due to the difficulty of obtaining consent and measuring outcomes. This study demonstrates that long-term oxytocin treatment is feasible and safe in this group, even with their elevated seizure risk. The discrepancy between null results on rating scales and positive signals in real-world social observations raises important questions about how we measure treatment outcomes in this population.","specificNumbers":"","methodology":"Randomized, double-blind, placebo-controlled crossover pilot study (UMIN000007250). Twenty-nine males aged 15–40 with ASD and comorbid intellectual disabilities participated. Each received 8 weeks of intranasal oxytocin (16 IU/day) and 8 weeks of placebo in crossover fashion. Primary outcome was the Childhood Autism Rating Scale. Secondary measures included multiple standardized behavioral assessments. Exploratory measures included direct observation of social interactions during play sessions and daily life. Plasma oxytocin concentrations were measured.","limitations":"This is a small pilot study (29 participants) not powered for definitive efficacy conclusions. The positive social interaction findings were from exploratory analyses, not pre-specified primary outcomes, increasing the risk of false positives. The crossover design with 8-week periods may have been complicated by carryover effects. The seizure event, while isolated, is concerning in a seizure-prone population and warrants monitoring in larger trials. Only males were included, and results may not generalize to females with ASD."},{"rthcId":"RPEP-03062","title":"Lactation Is a Risk Factor of Postpartum Heart Failure in Mice with Cardiomyocyte-specific Apelin Receptor (APJ) Overexpression.","authors":"Murata, Kazuya; Ishida, Junji; Ishimaru, Tomohiro; Mizukami, Hayase; Hamada, Juri; Saito, Chiaki; Fukamizu, Akiyoshi","year":2016,"journal":"The Journal of biological chemistry, 291(21), 11241-51","doi":"10.1074/jbc.M115.699009","pmid":"27033703","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Cardiomyocyte-specific overexpression of the APJ receptor in mice leads to cardiac hypertrophy and dysfunction. Pregnancy followed by lactation exacerbates these effects, causing postpartum cardiomyopathy characterized by cardiac fibrosis, lung congestion, pleural effusion, and abnormal breathing. Lactation impairs myocardial angiogenesis and disrupts angiogenic gene expression balance in APJ-TG mice.","whyItMatters":"Understanding how APJ receptor overexpression and lactation interact to cause postpartum heart failure can help identify new mechanisms and potential targets for preventing or treating postpartum cardiomyopathy in humans.","specificNumbers":"","methodology":"The study used genetically engineered mice with cardiomyocyte-specific APJ overexpression (APJ-TG). Cardiac function and pathology were assessed in male, non-pregnant female, and postpartum female mice subjected to pregnancy and lactation cycles. Molecular analyses evaluated gene expression related to heart function and angiogenesis.","limitations":"The study was conducted in a mouse model, which may not fully replicate human postpartum heart conditions. The exact molecular pathways linking APJ overexpression and lactation-induced heart failure require further investigation."},{"rthcId":"RPEP-03063","title":"The Neurobiological Impact of Ghrelin Suppression after Oesophagectomy.","authors":"Murphy, Conor F; le Roux, Carel W","year":2016,"journal":"International journal of molecular sciences, 18(1)","doi":"10.3390/ijms18010035","pmid":"28035969","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Postoperative ghrelin levels are acutely suppressed following oesophagectomy, which may influence neurobiological processes related to energy homeostasis and appetite regulation.","whyItMatters":"Understanding ghrelin suppression after oesophagectomy can help clarify its role in patient recovery, appetite control, and potential impacts on cancer-related metabolism and cachexia.","specificNumbers":"","methodology":"The study reviewed existing literature and data on ghrelin secretion changes after oesophagectomy and examined the hormone's neurobiological roles, particularly in the context of cancer and metabolic regulation.","limitations":"The study type and evidence strength are unspecified, limiting conclusions about causality; also, direct experimental data on neurobiological impacts post-surgery are lacking."},{"rthcId":"RPEP-03064","title":"Anti-proliferative and pro-apoptotic effects of GHRH antagonists in prostate cancer.","authors":"Muñoz-Moreno, Laura; Arenas, Maria Isabel; Carmena, María J; Schally, Andrew V; Sánchez-Chapado, Manuel; Prieto, Juan C; Bajo, Ana M","year":2016,"journal":"Oncotarget, 7(32), 52195-52206","doi":"10.18632/oncotarget.10710","pmid":"27448980","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GHRH antagonists JMR-132 and JV-1-38 inhibited proliferation and induced apoptosis in prostate cancer cell lines and tumors. They caused S-phase cell cycle arrest and altered expression of key regulatory proteins including p21, p53, Bax, Bcl2, CD44, Cyclin D1, c-myc, and caspase 3.","whyItMatters":"Understanding how GHRH antagonists inhibit prostate cancer growth and promote apoptosis could lead to new therapeutic strategies targeting hormone pathways in cancer. This expands potential treatment options beyond traditional hormone therapies.","specificNumbers":"","methodology":"The study used in vitro assays (MTT and BrdU) to measure cell viability and proliferation in non-tumoral and tumoral prostate cell lines. Cell cycle and apoptosis were analyzed in PC3 cells. Protein and gene expression changes were assessed by Western blot and RT-PCR in both cell cultures and an in vivo tumor model.","limitations":"The study does not specify clinical trial data or long-term effects in humans. The exact mechanisms and efficacy in diverse patient populations remain to be further validated."},{"rthcId":"RPEP-03065","title":"Skin-bacteria communication: Involvement of the neurohormone Calcitonin Gene Related Peptide (CGRP) in the regulation of Staphylococcus epidermidis virulence.","authors":"N'Diaye, Awa R; Leclerc, Camille; Kentache, Takfarinas; Hardouin, Julie; Poc, Cecile Duclairoir; Konto-Ghiorghi, Yoan; Chevalier, Sylvie; Lesouhaitier, Olivier; Feuilloley, Marc G J","year":2016,"journal":"Scientific reports, 6, 35379","doi":"10.1038/srep35379","pmid":"27739485","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CGRP at very low concentrations (-12 M) significantly stimulates Staphylococcus epidermidis virulence by increasing its adherence to keratinocytes and inducing interleukin 8 release, without altering secretion of classical virulence factors. The bacterial DnaK protein acts as the CGRP sensor, and the effects are mediated via MscL mechanosensitive channels, as shown by inhibition with gadolinium chloride.","whyItMatters":"Understanding how neurohormones like CGRP regulate skin bacteria virulence reveals new aspects of skin microbiome-host communication, which could inform treatments for skin infections or inflammatory conditions involving Staphylococcus epidermidis.","specificNumbers":"","methodology":"The study exposed Staphylococcus epidermidis and Staphylococcus aureus to CGRP and measured changes in bacterial virulence properties, including adherence, internalization, biofilm formation, and induction of immune responses in keratinocytes. Protein binding assays identified the bacterial CGRP receptor, and channel inhibitors were used to explore signaling mechanisms.","limitations":"The study does not specify the in vivo relevance or clinical impact of CGRP-induced changes in bacterial virulence, and the exact downstream signaling pathways remain to be fully elucidated."},{"rthcId":"RPEP-03066","title":"Skin-bacteria communication: Involvement of the neurohormone Calcitonin Gene Related Peptide (CGRP) in the regulation of Staphylococcus epidermidis virulence.","authors":"N'Diaye, Awa R; Leclerc, Camille; Kentache, Takfarinas; Hardouin, Julie; Poc, Cecile Duclairoir; Konto-Ghiorghi, Yoan; Chevalier, Sylvie; Lesouhaitier, Olivier; Feuilloley, Marc G J","year":2016,"journal":"Scientific reports, 6, 35379","doi":"10.1038/srep35379","pmid":"27739485","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CGRP at very low concentrations (-12 M) significantly stimulates Staphylococcus epidermidis virulence by increasing its adherence to keratinocytes and inducing interleukin 8 release, without altering secretion of classical virulence factors. The bacterial DnaK protein acts as the CGRP sensor, and the effects are mediated via MscL mechanosensitive channels, as shown by inhibition with gadolinium chloride.","whyItMatters":"Understanding how neurohormones like CGRP regulate skin bacteria virulence reveals new aspects of skin microbiome-host communication, which could inform treatments for skin infections or inflammatory conditions involving Staphylococcus epidermidis.","specificNumbers":"","methodology":"The study exposed Staphylococcus epidermidis and Staphylococcus aureus to CGRP and measured changes in bacterial virulence properties, including adherence, internalization, biofilm formation, and induction of immune responses in keratinocytes. Protein binding assays identified the bacterial CGRP receptor, and channel inhibitors were used to explore signaling mechanisms.","limitations":"The study does not specify the in vivo relevance or clinical impact of CGRP-induced changes in bacterial virulence, and the exact downstream signaling pathways remain to be fully elucidated."},{"rthcId":"RPEP-03067","title":"Novel Chemiluminescent Enzyme Immunoassays for Individual Quantification of 3 Endogenous Molecular Forms of Atrial Natriuretic Peptide in Human Plasma.","authors":"Nagai-Okatani, Chiaki; Kangawa, Kenji; Takashio, Seiji; Takahama, Hiroyuki; Hayashi, Tomohiro; Anzai, Toshihisa; Minamino, Naoto","year":2016,"journal":"The journal of applied laboratory medicine, 1(1), 47-59","doi":"10.1373/jalm.2016.020230","pmid":"33626798","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Three chemiluminescent enzyme immunoassays (CLEIAs) were developed using a novel PEGylation technique to reduce background noise, enabling accurate individual measurement of α-ANP, β-ANP, and proANP directly in plasma.\n\nIn patients with acute decompensated heart failure, β-ANP levels showed marked decreases during treatment, while proANP levels decreased only moderately. The ratio of β-ANP to total ANP was significantly lower at discharge compared to admission, whereas α-ANP and proANP ratios remained stable. These distinct patterns suggest β-ANP and proANP may offer complementary biomarker information beyond what BNP alone provides.","whyItMatters":"Current heart failure diagnosis relies heavily on BNP-based blood tests, but ANP — another cardiac hormone — exists in multiple forms that may behave differently during disease. Having tools to measure each ANP form separately opens a new window into heart failure monitoring and could eventually lead to more nuanced diagnostic and treatment approaches.","specificNumbers":"","methodology":"The researchers designed three plate-based chemiluminescent enzyme immunoassays, each targeting a different measurement: total ANP (sum of all three forms), β-ANP alone, and proANP alone. They added a single-step PEGylation modification to the antibody-binding step to minimize background signals. The assays were validated for sensitivity, specificity, reproducibility, and accuracy, and then applied to plasma samples from patients with acute decompensated heart failure collected during the course of treatment.","limitations":"The study focused on developing and validating the assay technology, so the clinical patient data shown is preliminary and the sample size is not clearly reported. The research was conducted in a specific population of acute decompensated heart failure patients, and it remains unclear how these assays would perform across different types and stages of heart failure. Long-term clinical utility and comparison with existing BNP assays in larger trials have not yet been established."},{"rthcId":"RPEP-03068","title":"The RNA-binding protein Musashi 1 stabilizes the oncotachykinin 1 mRNA in breast cancer cells to promote cell growth.","authors":"Nahas, George R; Murthy, Raghav G; Patel, Shyam A; Ganta, Teja; Greco, Steven J; Rameshwar, Pranela","year":2016,"journal":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 30(1), 149-59","doi":"10.1096/fj.15-278770","pmid":"26373800","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Musashi 1 (Msi1) binds to the 3' UTR of TAC1 mRNA in breast cancer cells, competing with microRNAs miR130a and miR206 to stabilize TAC1 mRNA and enhance its translation, thereby promoting tumor growth. Knockdown of Msi1 in breast cancer cells significantly reduced tumor growth in nude BALB/c mice.","whyItMatters":"Understanding how Musashi 1 stabilizes TAC1 mRNA reveals a novel regulatory mechanism in breast cancer progression, which could lead to new therapeutic targets to inhibit tumor growth.","specificNumbers":"","methodology":"The study used in vitro translational assays, mRNA stabilization analyses, protein-RNA interaction assays including RNA-shift and RNA supershift analyses, proteomic identification, reporter gene systems, and in vivo tumor growth experiments in nude BALB/c mice injected with Msi1-knockdown breast cancer cells.","limitations":"The exact clinical relevance and therapeutic potential require further validation in human studies, and the study did not specify the sample size or provide detailed quantitative data on Msi1 expression levels in patient tumors."},{"rthcId":"RPEP-03069","title":"Paneth cell α-defensins and enteric microbiota in health and disease.","authors":"Nakamura, Kiminori; Sakuragi, Naoya; Takakuwa, Akiko; Ayabe, Tokiyoshi","year":2016,"journal":"Bioscience of microbiota, food and health, 35(2), 57-67","doi":"10.12938/bmfh.2015-019","pmid":"27200259","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03070","title":"Predictors of weight-loss response with glucagon-like peptide-1 receptor agonist treatment among adolescents with severe obesity.","authors":"Nathan, B M; Rudser, K D; Abuzzahab, M J; Fox, C K; Coombes, B J; Bomberg, E M; Kelly, A S","year":2016,"journal":"Clinical obesity, 6(1), 73-8","doi":"10.1111/cob.12128","pmid":"26683756","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among adolescents with severe obesity treated with exenatide, female sex and higher baseline appetite were significant predictors of greater BMI reduction at 3 months, with females experiencing a -4.78% BMI change versus 0.76% in males (P = 0.007), and high appetite individuals showing a -4.28% change versus 1.02% in low appetite (P = 0.028).","whyItMatters":"Identifying who is most likely to benefit from GLP-1 receptor agonist treatment can help personalize obesity therapies for adolescents, improving outcomes and resource use.","specificNumbers":"","methodology":"Data from 32 adolescents across two similar clinical trials were pooled. Participants received exenatide injections starting at 5 mcg twice daily for one month, then 10 mcg twice daily for two months. BMI changes were analyzed using statistical models to identify predictors such as baseline BMI, appetite, sex, and side effects.","limitations":"The small sample size and short duration limit generalizability, and the study design was a pooled analysis rather than a randomized controlled trial specifically powered for predictors."},{"rthcId":"RPEP-03071","title":"Systematic review and meta-analysis of the effect of meal intake on postprandial appetite-related gastrointestinal hormones in obese children.","authors":"Nguo, K; Walker, K Z; Bonham, M P; Huggins, C E","year":2016,"journal":"International journal of obesity (2005), 40(4), 555-63","doi":"10.1038/ijo.2015.256","pmid":"26686004","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Obese children showed attenuated postprandial ghrelin and peptide YY (PYY) responses compared to healthy-weight children. Ghrelin normally drops after eating (signaling fullness), but this drop was blunted in obese children at both 60 and 120 minutes (p<0.05 for both). Similarly, PYY normally rises after eating (promoting satiety), but this rise was reduced in obese children at both time points. These altered peptide hormone responses suggest a physiological basis for impaired appetite regulation in childhood obesity.","whyItMatters":"Childhood obesity affects over 340 million children worldwide. This meta-analysis reveals that obese children have blunted responses in two key appetite-regulating peptides after meals — their bodies don't properly signal fullness. This suggests that treating childhood obesity may require approaches that address these hormonal imbalances, potentially including peptide-based therapies that restore normal ghrelin and PYY signaling.","specificNumbers":"9 studies · 32 test meal-hormone comparisons · 6 appetite hormones reviewed · ghrelin attenuated at 60 min (n=129) and 120 min (n=100) · PYY attenuated at 60 min (n=128) and 120 min (n=100) · all p<0.05 · 1,001 papers initially screened","methodology":"Systematic review and meta-analysis searching EMBASE, CINAHL Plus, OVID Medline, and Cochrane Library. Nine studies meeting inclusion criteria were analyzed, collectively reporting on six appetite hormones across 32 test meal-hormone comparisons. Meta-analyses compared pooled mean differences in postprandial ghrelin and PYY changes between obese and healthy-weight children.","limitations":"Only 9 studies met inclusion criteria, with relatively small combined sample sizes (100-129 participants per analysis). Insufficient studies reported on hormones beyond ghrelin and PYY, preventing meta-analysis of GLP-1, CCK, and others. The studies varied in meal composition and hormone measurement methods. Behavioral and clinical outcomes (actual food intake, weight trajectories) were not assessed in relation to the hormonal findings."},{"rthcId":"RPEP-03072","title":"Staphylokinase has distinct modes of interaction with antimicrobial peptides, modulating its plasminogen-activation properties.","authors":"Nguyen, Leonard T; Vogel, Hans J","year":2016,"journal":"Scientific reports, 6, 31817","doi":"10.1038/srep31817","pmid":"27554435","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The truncated form of staphylokinase (SakΔN10) shows improved affinity for antimicrobial peptides, with two distinct binding surfaces identified. Binding of certain peptides to these surfaces either inhibits or promotes Sak's plasminogen activation properties.","whyItMatters":"Understanding how staphylokinase interacts with antimicrobial peptides can inform the development of new therapeutic strategies targeting bacterial infections and modulating plasminogen activation.","specificNumbers":"","methodology":"The study used binding assays and molecular docking to analyze interactions between staphylokinase (full-length and truncated) and various antimicrobial peptides, assessing affinity and binding sites.","limitations":"The study did not specify the in vivo relevance or clinical implications of these interactions, and the exact physiological concentrations of peptides were not addressed."},{"rthcId":"RPEP-03073","title":"The role of human β-defensins in allergic diseases.","authors":"Niyonsaba, F; Kiatsurayanon, C; Ogawa, H","year":2016,"journal":"Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology, 46(12), 1522-1530","doi":"10.1111/cea.12843","pmid":"27790779","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Human β-defensins regulate immune cell activity and inflammatory responses, contributing to the development and progression of allergic diseases including atopic dermatitis, allergic rhinitis, asthma, and chronic rhinosinusitis.","whyItMatters":"Identifying the role of β-defensins in allergy mechanisms may help develop targeted therapies that modulate these peptides to treat or prevent allergic diseases.","specificNumbers":"","methodology":"This article is a review summarizing current research on the regulation and biological functions of human β-defensins and their involvement in allergic disease pathogenesis.","limitations":"As a review, it summarizes existing studies without new experimental data, and the evidence strength and study types vary across cited research."},{"rthcId":"RPEP-03074","title":"Altered Appetite-Mediating Hormone Concentrations Precede Compensatory Overeating After Severe, Short-Term Energy Deprivation in Healthy Adults.","authors":"O'Connor, Kristie L; Scisco, Jenna L; Smith, Tracey J; Young, Andrew J; Montain, Scott J; Price, Lori Lyn; Lieberman, Harris R; Karl, J Philip","year":2016,"journal":"The Journal of nutrition, 146(2), 209-17","doi":"10.3945/jn.115.217976","pmid":"26740683","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Short-term severe energy deprivation significantly suppressed fasting acyl ghrelin and insulin levels while increasing postprandial anorexigenic hormones such as GLP-1 and pancreatic polypeptide. These hormonal changes preceded a compensatory increase in ad libitum energy intake by approximately 811 kcal over 36 hours.","whyItMatters":"Understanding how appetite hormones respond to calorie deficits helps explain why people often overeat after dieting. This insight is important for developing strategies to manage weight regain and improve obesity treatments.","specificNumbers":"","methodology":"Twenty-one healthy adults underwent two 48-hour diet periods with controlled energy intake and increased energy expenditure through exercise. One period maintained energy balance, and the other induced a severe energy deficit (~3700 kcal). Appetite hormones and energy intake were measured after each period.","limitations":"The study had a small sample size of 21 young adults, limiting generalizability. The short duration (48 hours) may not reflect long-term hormonal responses or eating behaviors."},{"rthcId":"RPEP-03075","title":"T Cell Epitope Peptide Therapy for Allergic Diseases.","authors":"O'Hehir, Robyn E; Prickett, Sara R; Rolland, Jennifer M","year":2016,"journal":"Current allergy and asthma reports, 16(2), 14","doi":"10.1007/s11882-015-0587-0","pmid":"26768622","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"T cell epitope peptide therapy — using carefully selected short peptide fragments from major allergens — has shown encouraging results in randomized, double-blind, placebo-controlled clinical trials. The peptides are designed to bind a wide range of immune system MHC class II molecules, allowing them to induce tolerance across genetically diverse patient populations.\n\nTrials in cat allergy, house dust mite allergy, and grass pollen allergy have demonstrated significant efficacy with short treatment courses. The preferred delivery method is intradermal injection into non-inflamed skin, and adverse events have been inconsequential and non-systemic — a major safety advantage over traditional whole-allergen immunotherapy.","whyItMatters":"Traditional allergy immunotherapy requires years of regular injections with whole allergen extracts and carries a risk of severe allergic reactions. Peptide-based therapy could offer shorter treatment courses with better safety, since the peptide fragments are too small to trigger the IgE-mediated reactions that cause anaphylaxis. If successful, this approach could transform how hundreds of millions of allergy sufferers are treated.","specificNumbers":"","methodology":"This was a review of the field covering the progression from in vitro studies showing peptide-induced T cell anergy, through proof-of-concept mouse models, to current human clinical trials. The authors examined randomized, double-blind, placebo-controlled trials using mixtures of short allergen peptides or long contiguous overlapping peptides delivered intradermally.","limitations":"The exact immunological mechanisms driving tolerance are not fully resolved — T cell anergy, Th2 deletion, immune deviation, and regulatory T cell induction are all implicated but their relative contributions are unclear. The review was published in 2016, and some of the clinical programs discussed may have since advanced or been discontinued. Long-term durability of the tolerance effect needs more data."},{"rthcId":"RPEP-03076","title":"The Potential of Nasal Oxytocin Administration for Remediation of Autism Spectrum Disorders.","authors":"Okamoto, Yuko; Ishitobi, Makoto; Wada, Yuji; Kosaka, Hirotaka","year":2016,"journal":"CNS & neurological disorders drug targets, 15(5), 564-77","doi":null,"pmid":"27071789","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"All reviewed clinical trials confirmed that both single-dose and long-term intranasal oxytocin administration was well tolerated in individuals with ASD, with no severe adverse events reported. However, efficacy results were inconsistent:\n\n- Some studies reported significant improvement in core ASD symptoms including social-communicative deficits after long-term administration\n- Other studies showed no such improvement\n\nThe review identifies several potential factors influencing outcomes: dosage amount, frequency of administration, and participant characteristics (age, sex, intellectual ability). The authors also highlight unresolved questions about the pharmacokinetics — how intranasal oxytocin actually reaches and affects the central nervous system.","whyItMatters":"Autism spectrum disorder affects approximately 1-2% of children worldwide, and there are currently no FDA-approved medications targeting the core social communication difficulties. Oxytocin represents one of the most biologically plausible peptide-based approaches to this challenge, given its well-established role in social bonding and trust. Clarifying why some trials succeed while others fail is critical for developing effective oxytocin-based therapies.","specificNumbers":"","methodology":"This is a narrative review of published clinical trials investigating intranasal oxytocin in individuals with autism spectrum disorder. The authors analyzed findings from both single-dose and long-term administration studies, examining safety profiles, efficacy outcomes, and factors that may influence treatment response.","limitations":"The review covers a relatively small number of trials with varying designs, sample sizes, and outcome measures, making direct comparisons difficult. The inconsistent efficacy findings may reflect genuine heterogeneity in treatment response, differences in study methodology, or both. Critically, the mechanism by which intranasal oxytocin reaches the brain remains poorly understood — it's unclear how much of the nasal dose actually enters the central nervous system versus being absorbed into the bloodstream."},{"rthcId":"RPEP-03077","title":"Efficacy of oral meloxicam suspension for prevention of pain and inflammation following band and surgical castration in calves.","authors":"Olson, M E; Ralston, Brenda; Burwash, Les; Matheson-Bird, Heather; Allan, Nick D","year":2016,"journal":"BMC veterinary research, 12(1), 102","doi":"10.1186/s12917-016-0735-3","pmid":"27295955","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Meloxicam oral suspension at 1 mg/kg given 2 hours before band or surgical castration significantly reduced physiological pain markers (heart rate, plasma cortisol, substance P), behavioral signs of pain, and scrotal inflammation for up to 72 hours post-castration.","whyItMatters":"This study shows that oral meloxicam can effectively manage pain and inflammation in calves undergoing castration, improving animal welfare and potentially setting a standard for pain control in livestock procedures.","specificNumbers":"","methodology":"Two trials with 60 healthy Holstein calves (4-5 months old) compared meloxicam oral suspension (1 mg/kg) to saline given 2 hours before either band or surgical castration. Pain and inflammation were assessed using physiological measures, behavioral observations, and inflammation scoring over 3 days post-castration.","limitations":"The study was limited to young Holstein calves and only assessed short-term effects up to 3 days post-castration. Long-term outcomes and effects in other breeds or ages were not evaluated."},{"rthcId":"RPEP-03078","title":"Failure of sucrose replacement with the non-nutritive sweetener erythritol to alter GLP-1 or PYY release or test meal size in lean or obese people.","authors":"Overduin, Joost; Collet, Tinh-Hai; Medic, Nenad; Henning, Elana; Keogh, Julia M; Forsyth, Faye; Stephenson, Cheryl; Kanning, Marja W; Ruijschop, Rianne M A J; Farooqi, I Sadaf; van der Klaauw, Agatha A","year":2016,"journal":"Appetite, 107, 596-603","doi":"10.1016/j.appet.2016.09.009","pmid":"27620647","tags":["glp-1","gut-hormones"],"studyType":"rct","evidenceStrength":"moderate","keyFinding":"Replacing sucrose with the low-calorie bulk sweetener erythritol in test meals did not change post-meal GLP-1 or PYY gut hormone levels, and did not affect how much food people ate afterward or their preference for sweet foods. Both lean and obese participants showed similar gut hormone responses regardless of whether the meal contained sucrose or erythritol.\n\nThe one notable difference: when lean participants ate a larger-volume isocaloric erythritol meal, they reported less hunger than after the sucrose control meal (p=0.003) — likely a volume effect rather than a sweetener effect. This volume-related hunger reduction was not seen in obese participants.","whyItMatters":"GLP-1 and PYY are key gut hormones that signal fullness after eating. If artificial or low-calorie sweeteners disrupted these hormones, it could explain why some people overeat despite using sugar substitutes. This study shows erythritol does not interfere with these satiety signals — a reassuring finding for those using erythritol as a sugar replacement for weight management.","specificNumbers":"n=20 · 10 lean + 10 obese · 3-way crossover · No GLP-1/PYY difference vs sucrose · p=0.003 hunger reduction in lean (isocaloric meal only)","methodology":"Randomized three-way crossover study. Twenty volunteers (10 lean, 10 obese) each consumed three different test meals on separate days: a sucrose control meal, a same-volume meal with partial erythritol substitution, and a same-calorie meal with more erythritol (larger volume). Researchers measured blood levels of GLP-1, PYY, glucose, and insulin after each meal, along with hunger/satiety ratings and how much food participants ate at a subsequent ad libitum meal.","limitations":"Very small sample size (only 10 per group) limits statistical power and generalizability. The study measured acute, single-meal effects — long-term impacts of erythritol on appetite hormones and eating behavior remain unknown. The crossover design helps control for individual variation but the study was not blinded for meal volume differences."},{"rthcId":"RPEP-03079","title":"Comparison of TLR-2, TLR-4, and antimicrobial peptide levels in different lesions of acne vulgaris.","authors":"Ozlu, Emin; Karadag, Ayse Serap; Ozkanli, Seyma; Oguztuzun, Serpil; Kilic, Murat; Zemheri, Ebru; Akbulak, Ozge; Akdeniz, Necmettin","year":2016,"journal":"Cutaneous and ocular toxicology, 35(4), 300-9","doi":"10.3109/15569527.2015.1120742","pmid":"26695933","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"TLR-2, TLR-4, and hBD-1 expression levels differed significantly across all four skin regions examined (epidermis, dermis, inflammation area, and skin appendages) in acne lesions (p<0.05). Cathelicidin levels differed significantly only in the inflammation region.\n\nSpecifically, TLR-2 in the epidermis was lower in nodular lesions than in papules and comedones. TLR-2 in the inflammation region and dermis was significantly higher in papules compared to pustules. TLR-4 in the dermis was significantly lower in comedones compared to papules. hBD-1 in the epidermis was significantly higher in comedones compared to nodules. Cathelicidin expression in the inflammation region of comedones was significantly low.","whyItMatters":"Acne affects millions of people worldwide, yet treatment often relies on broad approaches like antibiotics or retinoids. Understanding that different lesion types have distinct immune and antimicrobial peptide profiles could lead to more personalized, targeted therapies. For example, treatments that boost cathelicidin in early comedonal lesions or modulate TLR-2 in inflammatory papules could be more effective than one-size-fits-all approaches.","specificNumbers":"","methodology":"Skin biopsies were collected from 80 patients with acne vulgaris — 20 each with papular, pustular, comedonal, and nodular lesions — along with 20 healthy volunteers as controls. Using immunohistochemistry, researchers measured the expression levels of TLR-2, TLR-4, hBD-1, and cathelicidin in four distinct skin areas: epidermis, dermis, inflammation region, and skin appendages. Results were compared between lesion types.","limitations":"The cross-sectional design captures a single time point and cannot show how peptide and receptor levels change as lesions develop or resolve. The study did not control for potential confounding factors like medications, skincare products, or diet. With 20 patients per lesion type, the sample size limits statistical power for subgroup analyses. No treatment outcomes were measured, so the clinical significance of the observed differences remains theoretical."},{"rthcId":"RPEP-03080","title":"Epitope mapping of anti-myelin oligodendrocyte glycoprotein (MOG) antibodies in a mouse model of multiple sclerosis: microwave-assisted synthesis of the peptide antigens and ELISA screening.","authors":"Pacini, Giulia; Ieronymaki, Matthaia; Nuti, Francesca; Sabatino, Giuseppina; Larregola, Maud; Aharoni, Rina; Papini, Anna Maria; Rovero, Paolo","year":2016,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 22(1), 52-8","doi":"10.1002/psc.2839","pmid":"26663200","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The study demonstrated a strong IgG antibody response against both the recombinant refolded MOG(1-117) protein and the immunodominant peptide MOG(35-55), while no antibody response was detected against other synthetic peptide fragments, indicating absence of intramolecular epitope spreading. Additionally, the recombinant protein bound antibodies more efficiently than the peptide, suggesting the presence of both linear and conformational epitopes within the MOG(35-55) sequence.","whyItMatters":"Understanding the specific antibody targets in multiple sclerosis models helps clarify disease mechanisms and can guide development of targeted therapies or diagnostics involving peptide antigens.","specificNumbers":"","methodology":"Researchers cloned and expressed the extracellular domain of MOG (1-117) in E. coli, refolded it on-column, and synthesized five overlapping peptides using microwave-assisted solid-phase synthesis. They then performed ELISA assays on sera from naïve and EAE-induced C57BL/6 mice to detect IgG antibody binding to the recombinant protein and peptides.","limitations":"The study was conducted in a mouse model, which may not fully replicate human multiple sclerosis antibody responses. The sample size and detailed statistical analysis were not specified."},{"rthcId":"RPEP-03081","title":"The Effect of the Addition of Encapsulated Collagen Hydrolysate on Some Quality Characteristics of Sucuk.","authors":"Palamutoğlu, Recep; Sariçoban, Cemalettin","year":2016,"journal":"Korean journal for food science of animal resources, 36(6), 807-818","doi":"10.5851/kosfa.2016.36.6.807","pmid":"28115893","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Encapsulated fish collagen hydrolysate added to sucuk significantly increased antioxidant activity (up to 40.48%) and hardness (up to 35.83 N) compared to control and non-encapsulated peptide groups. It also lowered pH and increased lactic acid concentration during the 28-day ripening period.","whyItMatters":"Improving the functional and sensory qualities of fermented meat products with bioactive peptides like collagen hydrolysates can enhance their health benefits and consumer acceptance.","specificNumbers":"","methodology":"Six sucuk dough groups were prepared with different treatments: control, peptide, and four encapsulated peptide formulations varying in maltodextrin type and peptide ratio. The sausages were naturally fermented for 28 days, and quality parameters such as pH, lactic acid, moisture, antioxidant activity, ACE inhibition, TBA values, and hardness were measured.","limitations":"The study did not specify the study type or sample size, limiting the ability to generalize results. Also, sensory evaluation and long-term storage effects were not reported."},{"rthcId":"RPEP-03082","title":"Antimicrobial peptides - a part of innate immunity.","authors":"Palatsi, Riitta; Kelhälä, Hanna-Leena","year":2016,"journal":"Duodecim; laaketieteellinen aikakauskirja, 132(19), 1790-6","doi":null,"pmid":"29188973","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"AMPs are evolutionarily conserved molecules produced by diverse human tissues with distinct spectra, exhibiting antimicrobial activity through membrane interaction. They may also contribute to the pathogenesis of neurodegenerative diseases and type 2 diabetes.","whyItMatters":"Understanding AMPs enhances our knowledge of innate immunity and could lead to novel treatments for infections and chronic diseases involving immune dysfunction.","specificNumbers":"","methodology":"This article reviews existing knowledge on antimicrobial peptides, summarizing their distribution, structural features, and potential roles in human health and disease.","limitations":"The study is a review without new experimental data, and the evidence strength and study type are not specified, limiting conclusions on clinical applications."},{"rthcId":"RPEP-03083","title":"A Spatiotemporal Profile of In Vivo Cerebral Blood Flow Changes Following Intranasal Oxytocin in Humans.","authors":"Paloyelis, Yannis; Doyle, Orla M; Zelaya, Fernando O; Maltezos, Stefanos; Williams, Steven C; Fotopoulou, Aikaterini; Howard, Matthew A","year":2016,"journal":"Biological psychiatry, 79(8), 693-705","doi":"10.1016/j.biopsych.2014.10.005","pmid":"25499958","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Intranasal oxytocin administration (40 IU) induced sustained increases in resting regional cerebral blood flow in brain regions associated with oxytocin receptors and social cognition, with peak effects occurring between 39 and 51 minutes post-administration.","whyItMatters":"Understanding the timing and brain regions affected by intranasal oxytocin is crucial for optimizing its use in treating social impairments in neuropsychiatric disorders such as autism.","specificNumbers":"","methodology":"In a placebo-controlled, double-blind study, 32 healthy men received 40 IU of intranasal oxytocin or placebo. Resting regional cerebral blood flow was measured using arterial spin labeling MRI before and up to 78 minutes after treatment. Data were analyzed using mass univariate and multivariate pattern recognition techniques.","limitations":"The study included only healthy men, limiting generalizability to women or clinical populations. The sample size was moderate, and the study did not assess behavioral outcomes directly."},{"rthcId":"RPEP-03084","title":"Adoptive transfer of M2 macrophages reduces neuropathic pain via opioid peptides.","authors":"Pannell, Maria; Labuz, Dominika; Celik, Melih Ö; Keye, Jacqueline; Batra, Arvind; Siegmund, Britta; Machelska, Halina","year":2016,"journal":"Journal of neuroinflammation, 13(1), 262","doi":null,"pmid":"27717401","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"M2 macrophages contained and released significantly higher amounts of the opioid peptides Met-enkephalin, dynorphin A (1-17), and β-endorphin compared to unstimulated M0 and pro-inflammatory M1 macrophages.\n\nWhen 5 × 10⁵ M2 macrophages were injected perineurally at the sciatic nerve injury site on days 14 and 15 after chronic constriction injury, they significantly reduced mechanical hypersensitivity following the second injection. This analgesic effect was reversed by perineurally applied naloxone methiodide (an opioid receptor antagonist that doesn't cross the blood-brain barrier), confirming it was mediated by local opioid receptor activation.\n\nImportantly, M2 cells only reduced mechanical pain — not heat hypersensitivity — and had no effect in sham-operated animals. Neither M0 nor M1 macrophages altered pain sensitivity. Fluorescent tracking showed that transferred cells remained at the nerve and maintained their phenotype.","whyItMatters":"Neuropathic pain is notoriously difficult to treat, and current opioid medications carry serious risks of addiction and side effects. This study shows that the body's own immune cells can be harnessed to deliver natural opioid peptides directly to the site of nerve injury, potentially offering pain relief without systemic opioid exposure. This cell-based approach could represent a fundamentally different strategy for managing chronic nerve pain.","specificNumbers":"","methodology":"Mouse bone marrow-derived cells were cultured as M0 (unstimulated), M1 (stimulated with LPS and interferon-γ), or M2 (stimulated with interleukin-4) macrophages. Phenotypes were verified by flow cytometry and cytokine profiling. Opioid peptide levels were measured by radioimmunoassay and enzyme immunoassay. Chronic constriction injury of the sciatic nerve served as the neuropathic pain model. Polarized macrophages (5 × 10⁵ cells) were injected perineurally on days 14 and 15 post-surgery. Pain was assessed with von Frey filaments (mechanical) and Hargreaves test (heat). Fluorescently stained cells were tracked ex vivo to confirm retention and phenotype preservation.","limitations":"The study was conducted in mice using a specific nerve injury model, and results may not translate directly to human neuropathic pain conditions. M2 macrophages only reduced mechanical pain, not heat sensitivity, suggesting they address only certain pain modalities. The effect required two injections and was assessed short-term; durability of pain relief is unknown. The feasibility of harvesting, polarizing, and transplanting a patient's own macrophages for clinical use remains to be determined."},{"rthcId":"RPEP-03085","title":"Role of the ACE2/Angiotensin 1-7 Axis of the Renin-Angiotensin System in Heart Failure.","authors":"Patel, Vaibhav B; Zhong, Jiu-Chang; Grant, Maria B; Oudit, Gavin Y","year":2016,"journal":"Circulation research, 118(8), 1313-26","doi":"10.1161/CIRCRESAHA.116.307708","pmid":"27081112","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03086","title":"Cathelicidins in the Tasmanian devil (Sarcophilus harrisii).","authors":"Peel, E; Cheng, Y; Djordjevic, J T; Fox, S; Sorrell, T C; Belov, K","year":2016,"journal":"Scientific reports, 6, 35019","doi":"10.1038/srep35019","pmid":"27725697","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Six cathelicidin peptides were characterized in Tasmanian devils. Saha-CATH5 and Saha-CATH6 showed broad-spectrum antibacterial activity, killing methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecalis (VRE). Saha-CATH3 had antifungal activity. Saha-CATH5 and 6 were toxic to human A549 cells at 500 μg/mL — over 7 times the pathogen-killing concentration. All six cathelicidins were widely expressed across immune tissues, digestive tract, respiratory tract, reproductive tract, milk, and pouch lining, indicating broad innate immune roles.","whyItMatters":"The antibiotic resistance crisis demands new antimicrobial approaches, and marsupial immune systems — evolved to protect the most vulnerable babies imaginable — represent an untapped source. Discovering peptides that kill both MRSA and VRE (two of the most dangerous hospital superbugs) with a good safety margin is significant. Marsupial peptides are structurally distinct from human cathelicidins, meaning bacteria haven't been exposed to them, potentially making resistance less likely to develop quickly.","specificNumbers":"","methodology":"Cathelicidin genes were identified and characterized from Tasmanian devil genomic data. Synthetic peptides were produced and tested for antimicrobial activity against bacterial and fungal pathogens identified in the pouch microbiome, including antibiotic-resistant clinical isolates (MRSA, VRE). Cytotoxicity was assessed using human A549 lung epithelial cells. Tissue expression patterns were mapped to understand the peptides' roles in innate immunity and maternal-to-offspring immune transfer.","limitations":"In vitro antimicrobial and cytotoxicity testing only — no in vivo efficacy studies were performed. Three of six cathelicidins showed no activity against tested organisms (though they were widely expressed, suggesting unidentified roles). The A549 cytotoxicity assay represents only one cell type. Stability, pharmacokinetics, and immunogenicity of Tasmanian devil peptides in mammalian systems were not assessed. The tested pathogens were limited to selected strains, and activity against Gram-negative superbugs was not specifically reported."},{"rthcId":"RPEP-03087","title":"Safety and Tolerability of Glucagon-Like Peptide-1 Receptor Agonists Utilizing Data from the Exenatide Clinical Trial Development Program.","authors":"Peng, Hui; Want, Laura L; Aroda, Vanita R","year":2016,"journal":"Current diabetes reports, 16(5), 44","doi":"10.1007/s11892-016-0728-4","pmid":"27037706","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 receptor agonists, particularly exenatide, demonstrate a favorable safety and tolerability profile with low incidence of hypoglycemia and no significant adverse effects on pancreatic, thyroid, or cardiovascular health based on clinical trial data.","whyItMatters":"Understanding the safety profile of GLP-1 receptor agonists is crucial for optimizing treatment in type 2 diabetes, ensuring patient safety while benefiting from improved blood sugar control and weight loss.","specificNumbers":"","methodology":"The article reviews safety and tolerability data from the exenatide clinical trial development program, analyzing comparative risks and clinical outcomes related to hypoglycemia, pancreatic, thyroid, and cardiovascular safety.","limitations":"The study is a review and does not present new experimental data; evidence strength and study type are unspecified, which may limit definitive conclusions."},{"rthcId":"RPEP-03088","title":"Serum thymosin α 1 levels in patients with chronic inflammatory autoimmune diseases.","authors":"Pica, F; Chimenti, M S; Gaziano, R; Buè, C; Casalinuovo, I A; Triggianese, P; Conigliaro, P; Di Carlo, D; Cordero, V; Adorno, G; Volpi, A; Perricone, R; Garaci, E","year":2016,"journal":"Clinical and experimental immunology, 186(1), 39-45","doi":"10.1111/cei.12833","pmid":"27350088","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Serum thymosin alpha 1 levels are significantly reduced in patients with chronic inflammatory autoimmune diseases compared to healthy controls, with the lowest levels observed in psoriatic arthritis patients. Treatment with disease-modifying anti-rheumatic drugs plus steroids was associated with higher Tα1 levels than other treatments, although levels remained below those of healthy individuals.","whyItMatters":"Understanding Tα1 levels in autoimmune diseases could help clarify its role in immune regulation and inflammation, potentially guiding new therapeutic approaches or biomarkers for disease activity.","specificNumbers":"","methodology":"The study analyzed serum Tα1 levels using ELISA in 120 healthy controls and 200 patients with psoriatic arthritis, rheumatoid arthritis, or systemic lupus erythematosus. Data were correlated with demographic and clinical characteristics, including treatment regimens.","limitations":"The study design and evidence strength are not specified, and the cross-sectional nature limits conclusions about causality. The sample size for some disease groups was relatively small, and treatment effects require further prospective validation."},{"rthcId":"RPEP-03089","title":"The Role of Cathelicidin LL-37 in Cancer Development.","authors":"Piktel, Ewelina; Niemirowicz, Katarzyna; Wnorowska, Urszula; Wątek, Marzena; Wollny, Tomasz; Głuszek, Katarzyna; Góźdź, Stanisław; Levental, Ilya; Bucki, Robert","year":2016,"journal":"Archivum immunologiae et therapiae experimentalis, 64(1), 33-46","doi":"10.1007/s00005-015-0359-5","pmid":"26395996","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03090","title":"A Direct Neurokinin B Projection from the Arcuate Nucleus Regulates Magnocellular Vasopressin Cells of the Supraoptic Nucleus.","authors":"Pineda, R; Sabatier, N; Ludwig, M; Millar, R P; Leng, G","year":2016,"journal":"Journal of neuroendocrinology, 28(4)","doi":"10.1111/jne.12342","pmid":"26610724","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Neurokinin B-expressing neurons in the arcuate nucleus project directly to magnocellular vasopressin neurons in the supraoptic nucleus and paraventricular nucleus, activating them via NK3 receptors and increasing vasopressin secretion without affecting oxytocin neurons.","whyItMatters":"Understanding how neurokinin B neurons regulate vasopressin secretion provides insight into brain control of fluid balance and blood pressure, which may inform treatments for related disorders.","specificNumbers":"","methodology":"The study used immunohistochemistry to identify NK3 receptor and NKB expression in rat brain regions, retrograde and anterograde neuronal tracing to map projections from arcuate nucleus neurons to vasopressin neurons, and intracerebroventricular injection of an NK3R agonist to measure vasopressin neuron activity in vivo.","limitations":"The study was conducted in rodents, so findings may not fully translate to humans; the exact physiological consequences of this pathway in living organisms require further exploration."},{"rthcId":"RPEP-03091","title":"Incretin-based therapy and acute cholecystitis: a review of case reports and EudraVigilance spontaneous adverse drug reaction reporting database.","authors":"Pizzimenti, V; Giandalia, A; Cucinotta, D; Russo, G T; Smits, M; Cutroneo, P M; Trifirò, G","year":2016,"journal":"Journal of clinical pharmacy and therapeutics, 41(2), 116-8","doi":"10.1111/jcpt.12373","pmid":"26936090","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Pharmacovigilance data from the EudraVigilance database identified 200 serious adverse drug reaction reports of cholecystitis associated with incretin-based therapies. Mechanisms such as inhibition of gallbladder contraction and rapid weight loss may contribute to this increased risk.","whyItMatters":"Understanding the potential gallbladder risks of incretin drugs helps clinicians better evaluate patient safety and manage diabetes treatment plans effectively.","specificNumbers":"","methodology":"The study reviewed spontaneous adverse drug reaction reports from the EudraVigilance database and existing scientific literature to assess the association between incretin-based therapies and acute cholecystitis.","limitations":"The study relies on spontaneous reporting data, which may be subject to underreporting and lacks controlled clinical trial confirmation."},{"rthcId":"RPEP-03092","title":"Role of fosaprepitant, a neurokinin Type 1 receptor antagonist, in morphine-induced antinociception in rats.","authors":"Prasoon, Pranav; Gupta, Shivani; Kumar, Rahul; Gautam, Mayank; Kaler, Saroj; Ray, Subrata Basu","year":2016,"journal":"Indian journal of pharmacology, 48(4), 394-398","doi":null,"pmid":"27756950","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In Sprague-Dawley rats treated for 7 days:\n\n- Morphine alone produced pain relief on day 1 that diminished by day 4, indicating tolerance development\n- Co-administration of fosaprepitant (30 mg/kg daily) with morphine (10 mg/kg twice daily) attenuated tolerance development (days 1 and 3) and maintained pain relief through days 1-4 compared to controls\n- Spinal cord immunohistochemistry showed increased substance P expression in the morphine + fosaprepitant group\n- CGRP (calcitonin gene-related peptide) expression was also assessed\n- The enhanced analgesia is likely linked to decreased release of substance P from presynaptic terminals in the spinal cord","whyItMatters":"The opioid crisis has highlighted the urgent need for strategies that improve pain relief while reducing opioid dose escalation. Fosaprepitant is already FDA-approved and widely used for preventing chemotherapy-induced nausea. If it can also slow morphine tolerance development in humans, it could be quickly repurposed as an adjunct to opioid therapy — potentially allowing patients to maintain pain relief at lower opioid doses and reducing the risks of dependence and overdose.","specificNumbers":"","methodology":"Sprague-Dawley rats received morphine (10 mg/kg twice daily) and/or fosaprepitant (30 mg/kg once daily) via injection for 7 days. Pain threshold was measured using the hot plate test (measuring how quickly rats respond to a heated surface). Spinal cord tissue was analyzed by immunohistochemistry to measure expression of substance P and CGRP neuropeptides.","limitations":"This is an animal study with rats — results may not translate to humans. The sample size per group is not specified in the abstract. The 7-day treatment period is short and may not reflect long-term tolerance patterns. The mechanism (decreased SP release from presynaptic terminals) is proposed but not directly proven. The specific doses used in rats do not directly translate to human dosing. No behavioral tests beyond the hot plate test were used to assess pain."},{"rthcId":"RPEP-03093","title":"Intranasal Oxytocin Failed to Affect Chimpanzee (Pan troglodytes) Social Behavior.","authors":"Proctor, Darby; Calcutt, Sarah E; Burke, Kimberly; de Waal, Frans B M","year":2016,"journal":"Animal behavior and cognition, 3(3), 150-158","doi":"10.12966/abc.04.08.2016","pmid":"28845444","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Intranasal administration of oxytocin to captive chimpanzees did not produce measurable changes in their social behavior compared to placebo. No significant behavioral differences were observed in a socially complex environment.","whyItMatters":"Understanding oxytocin's effects on social behavior in primates helps evaluate its potential as a treatment for social deficits in humans, such as in Autism Spectrum Disorders. Negative findings highlight challenges in translating lab results to real-world social contexts.","specificNumbers":"","methodology":"The study used a within-subject design where eight socially housed chimpanzees received intranasal oxytocin or placebo. An experimenter blind to treatment conditions recorded social behaviors after administration in a naturalistic group setting.","limitations":"The small sample size and uncertainty about the effective oxytocin dose and timing in chimpanzees limit the conclusions. The study also did not measure oxytocin levels in the brain to confirm uptake."},{"rthcId":"RPEP-03094","title":"Oxytocin enhances gaze-following responses to videos of natural social behavior in adult male rhesus monkeys.","authors":"Putnam, P T; Roman, J M; Zimmerman, P E; Gothard, K M","year":2016,"journal":"Psychoneuroendocrinology, 72, 47-53","doi":"10.1016/j.psyneuen.2016.05.016","pmid":"27343726","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Intranasal administration of 50 IU oxytocin significantly increased the frequency of gaze-following saccades in adult male rhesus monkeys viewing videos of conspecifics, indicating enhanced social engagement rather than merely increased perceptual salience of eyes.","whyItMatters":"Understanding how oxytocin influences social behaviors like gaze following can inform treatments for social deficits in disorders such as autism and improve our knowledge of social cognition mechanisms.","specificNumbers":"","methodology":"Four adult male rhesus monkeys were repeatedly shown videos of conspecifics displaying natural behaviors before and after receiving intranasal oxytocin or saline. Gaze-following saccades were measured to assess social attention.","limitations":"The small sample size of four monkeys limits generalizability, and the study design details and evidence strength were not specified, which may affect the robustness of conclusions."},{"rthcId":"RPEP-03095","title":"Development of a Backbone Cyclic Peptide Library as Potential Antiparasitic Therapeutics Using Microwave Irradiation.","authors":"Qvit, Nir; Kornfeld, Opher S","year":2016,"journal":"Journal of visualized experiments : JoVE, e53589","doi":"10.3791/53589","pmid":"26863382","tags":["cyclic-peptides","peptide-synthesis","antiparasitic"],"studyType":"methods-protocol","evidenceStrength":"early-preclinical","keyFinding":"The researchers developed a detailed protocol for building a library of backbone cyclic peptides using microwave-assisted synthesis, which dramatically speeds up the chemical reactions compared to conventional methods. The peptides were designed to target protein-protein interactions in the Leishmania parasite (which causes leishmaniasis) by focusing on sequences conserved in the parasite but absent from the human host.\n\nThe library approach is key: all cyclic peptides share the same amino acid sequence but differ in ring size and position, systematically varying the 3D shape. This allows researchers to screen for the most biologically active conformation without needing to predict it computationally — a notoriously difficult problem for cyclic peptides.","whyItMatters":"Protein-protein interactions drive most biological processes but are extremely hard to disrupt with conventional drugs because the binding surfaces are large and flat. Cyclic peptides are promising because cyclization improves their stability and ability to enter cells, but finding the right ring shape is challenging. This microwave-based method makes it fast and affordable to generate many conformational variants at once, accelerating the search for effective antiparasitic peptides.","specificNumbers":"Backbone cyclic peptides with varied ring sizes · Microwave irradiation reduces reaction times · Targets Leishmania LACK protein · Conserved parasite sequences not found in host","methodology":"Rational drug design was used to identify conserved sequences in the Leishmania LACK protein that differ from the mammalian homolog. These sequences were used as templates for backbone cyclic peptides. A library was synthesized with varying ring sizes using microwave irradiation to accelerate the cyclization reactions. The protocol is presented as a reproducible video method.","limitations":"This is a methods paper describing synthesis protocols — no biological activity data (antiparasitic efficacy, cell permeability, toxicity) are presented. The peptides are candidates for screening, not validated therapeutics. The approach is demonstrated for one parasite target and may need adaptation for others."},{"rthcId":"RPEP-03096","title":"GLP-1 as a target for therapeutic intervention.","authors":"Rajeev, Surya Panicker; Wilding, John","year":2016,"journal":"Current opinion in pharmacology, 31, 44-49","doi":"10.1016/j.coph.2016.08.005","pmid":"27591964","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 receptor agonists reduce HbA1c by 1-2% and body weight by 2-3 kg in type 2 diabetes patients. Liraglutide at higher doses leads to greater weight loss and is approved for obesity management. Combination therapies with basal insulin are now available.","whyItMatters":"GLP-1 receptor agonists offer a dual benefit of improving blood sugar control and aiding weight loss, addressing two major challenges in type 2 diabetes management.","specificNumbers":"","methodology":"This is a review article summarizing current knowledge and clinical data on GLP-1 receptor agonists used in type 2 diabetes treatment.","limitations":"The review does not specify study designs or strength of evidence, and long-term effects and safety profiles require further research."},{"rthcId":"RPEP-03097","title":"Type I collagen and its daughter peptides for targeting mucosal healing in ulcerative colitis: A new treatment strategy.","authors":"Ramadass, Satiesh Kumar; Jabaris, Sugin Lal; Perumal, Ramesh Kannan; HairulIslam, Villianur Ibrahim; Gopinath, Arun; Madhan, Balaraman","year":2016,"journal":"European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 91, 216-24","doi":"10.1016/j.ejps.2016.05.015","pmid":"27185300","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Type I collagen and collagen hydrolysate significantly reduced rectal bleeding, down-regulated VEGF and proinflammatory cytokines (TNF-α, IL-1β, IL-6), and improved mucosal healing compared to mesalamine and untreated controls in a dextran sodium sulfate-induced colitis mouse model.","whyItMatters":"Current ulcerative colitis treatments focus on reducing inflammation but do not directly heal mucosal ulcers. Collagen-based therapies could offer a new approach to promote tissue repair and improve patient outcomes.","specificNumbers":"","methodology":"The study used a dextran sodium sulfate-induced colitis mouse model to simulate ulcerative colitis. Treatments with type I collagen, collagen hydrolysate, mesalamine, or no treatment were administered, and clinical, molecular, and histological assessments were conducted on day 10.","limitations":"The study was conducted in a mouse model, so results may not fully translate to humans; the exact study type and evidence strength were not specified."},{"rthcId":"RPEP-03098","title":"Environmental enrichment induces behavioural disturbances in neuropeptide Y knockout mice.","authors":"Reichmann, Florian; Wegerer, Vanessa; Jain, Piyush; Mayerhofer, Raphaela; Hassan, Ahmed M; Fröhlich, Esther E; Bock, Elisabeth; Pritz, Elisabeth; Herzog, Herbert; Holzer, Peter; Leitinger, Gerd","year":2016,"journal":"Scientific reports, 6, 28182","doi":"10.1038/srep28182","pmid":"27305846","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In wildtype mice, environmental enrichment reduced anxiety and decreased central glucocorticoid receptor expression — classic beneficial effects. In NPY knockout mice, these benefits were completely absent. Instead, NPY-KO mice showed multiple adverse responses to enrichment: altered EE item preferences, exaggerated stress-induced hyperthermia, impaired spatial memory, higher hippocampal BDNF mRNA levels, and altered hippocampal synaptic plasticity.\n\nMolecular and morphological changes were observed in both the amygdala and hippocampus of NPY-KO mice, suggesting NPY normally acts in these brain regions to buffer environmental stimulation. The authors propose that without NPY, the arousal and novelty inherent in enriched environments becomes overwhelming rather than beneficial — converting a positive experience into a negative one.","whyItMatters":"Environmental enrichment is one of the most robust interventions for improving brain health in animal models, and the human equivalent — living in stimulating, socially rich environments — is associated with cognitive reserve and reduced dementia risk. This study reveals that NPY is a key molecular mediator of these benefits. For conditions where NPY signaling is impaired (PTSD, anxiety disorders, chronic stress), this explains why some individuals may not benefit from environmental interventions. It also opens the door to 'enviromimetic' drugs that could pharmacologically reproduce the brain benefits of enriched environments.","specificNumbers":"","methodology":"NPY knockout mice and wildtype C57BL/6 controls were housed in either standard or enriched environments. Behavioral assessments included anxiety tests, spatial memory (maze learning), stress-induced hyperthermia, and enrichment item preference. Molecular analysis measured glucocorticoid receptor expression, BDNF mRNA levels, and synaptic plasticity markers. Brain morphology was examined in the amygdala and hippocampus.","limitations":"The study used complete NPY knockout mice, which may have developmental compensations that don't reflect acute NPY depletion. Sample sizes were not specified in the abstract. The enrichment paradigm in laboratory mice may not fully model the complexity of human environmental experiences. The mechanism by which NPY absence converts enrichment from beneficial to harmful was not fully elucidated. The concept of 'enviromimetics' remains purely theoretical."},{"rthcId":"RPEP-03099","title":"Neuropeptide Y: A stressful review.","authors":"Reichmann, Florian; Holzer, Peter","year":2016,"journal":"Neuropeptides, 55, 99-109","doi":"10.1016/j.npep.2015.09.008","pmid":"26441327","tags":[],"studyType":"Narrative Review","evidenceStrength":"Moderate","keyFinding":"Neuropeptide Y (NPY) is a key stress-buffering peptide in the brain with anxiolytic, stress-relieving, and neuroprotective properties. Stress alters NPY production in specific brain regions, with the direction and magnitude varying by stress type and duration.\n\nNPY acts through four receptor subtypes with opposing effects: Y1 receptor activation reduces anxiety while Y2 receptor activation increases it. Higher NPY levels correlate with better stress coping and resilience, while low NPY is linked to PTSD vulnerability and behavioral disruption in animal models. NPY gene polymorphisms in humans predict impaired stress processing and increased neuropsychiatric disease risk. The peptide also shows neuroprotective roles in Alzheimer's, Parkinson's, and Huntington's disease.","whyItMatters":"Stress-related disorders — anxiety, PTSD, and depression — are among the most common and costly health conditions globally. NPY is emerging as a central biological mechanism that determines whether someone copes well with stress or develops pathological responses. Understanding the NPY system could lead to fundamentally new treatments that enhance resilience rather than just suppressing symptoms, and its neuroprotective properties add a potential second application in neurodegenerative diseases.","specificNumbers":"4 receptor subtypes (Y1, Y2, Y4, Y5) · Y1 = anxiolytic, Y2 = anxiogenic · NPY expressed in brainstem, hypothalamus, limbic system · Negative correlation between NPY and PTSD-like behavior · Gene polymorphisms predict neuropsychiatric risk","methodology":"This is a narrative review synthesizing evidence from animal stress models (including PTSD paradigms), human genetic association studies, neuroanatomical mapping, and receptor pharmacology research. The authors integrate findings across stress physiology, emotional behavior, feeding regulation, and neurodegenerative disease contexts.","limitations":"As a narrative review, this paper summarizes existing evidence but does not present new data or perform a systematic meta-analysis. Most of the mechanistic evidence comes from animal models, and translating NPY-based therapies to humans faces significant delivery challenges (NPY doesn't easily cross the blood-brain barrier). The receptor subtype complexity (Y1 anxiolytic vs Y2 anxiogenic) makes drug development complicated."},{"rthcId":"RPEP-03100","title":"Rapid Optimization of Mcl-1 Inhibitors using Stapled Peptide Libraries Including Non-Natural Side Chains.","authors":"Rezaei Araghi, Raheleh; Ryan, Jeremy A; Letai, Anthony; Keating, Amy E","year":2016,"journal":"ACS chemical biology, 11(5), 1238-44","doi":"10.1021/acschembio.5b01002","pmid":"26854535","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The study identified a stapled peptide, M3d, with enhanced binding affinity and selectivity for Mcl-1, capable of inducing mitochondrial permeabilization in Mcl-1 dependent cancer cell lines. The use of non-natural amino acid substitutions in a hydrocarbon-stapled helix improved peptide stability and potency.","whyItMatters":"This method allows rapid optimization of peptide inhibitors targeting protein-protein interactions, which are challenging drug targets. Improving Mcl-1 inhibitors could lead to better treatments for chemoresistant cancers.","specificNumbers":"","methodology":"The researchers synthesized a library of stapled peptides incorporating various non-natural amino acid substitutions and screened them for binding affinity to Mcl-1. They used a fixed hydrocarbon staple to stabilize the alpha-helical structure and assessed peptide potency in cell-based assays.","limitations":"The study does not specify clinical efficacy or safety data, and the exact study type and evidence strength are not detailed. Further in vivo validation is needed."},{"rthcId":"RPEP-03101","title":"Reduced cytotoxicity and enhanced bioactivity of cationic antimicrobial peptides liposomes in cell cultures and 3D epidermis model against HSV.","authors":"Ron-Doitch, Sapir; Sawodny, Beate; Kühbacher, Andreas; David, Mirjam M Nordling; Samanta, Ayan; Phopase, Jaywant; Burger-Kentischer, Anke; Griffith, May; Golomb, Gershon; Rupp, Steffen","year":2016,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 229, 163-171","doi":"10.1016/j.jconrel.2016.03.025","pmid":"27012977","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Encapsulation of the antimicrobial peptide LL-37 within liposomes significantly reduced its cytotoxicity and enhanced its antiviral activity against HSV-1 in both human keratinocyte cultures and a 3D epidermis model. Liposomal LL-37 demonstrated improved cellular uptake, stability, and a wider therapeutic window compared to free peptide or liposomal indolicidin.","whyItMatters":"This research suggests a promising delivery method to improve the safety and effectiveness of antimicrobial peptides for treating viral infections like herpes, potentially leading to better therapies with fewer side effects.","specificNumbers":"","methodology":"The study formulated nano-sized liposomes containing LL-37 and indolicidin peptides, characterized their physicochemical properties, and assessed cellular uptake, cytotoxicity, and antiviral efficacy in human keratinocyte cell lines and a 3D epidermis model infected with HSV-1.","limitations":"The study was conducted in vitro and in a 3D skin model, so further in vivo studies are needed to confirm safety and efficacy in living organisms. The exact clinical relevance and long-term effects remain to be established."},{"rthcId":"RPEP-03102","title":"Targeting \"Undruggable\" Proteins: Design of Synthetic Cyclopeptides.","authors":"Russo, Anna; Aiello, Carmela; Grieco, Paolo; Marasco, Daniela","year":2016,"journal":"Current medicinal chemistry, 23(8), 748-62","doi":null,"pmid":"26758797","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Synthetic macrocyclic peptides can effectively mimic secondary structures involved in protein-protein interactions (PPIs), which are often considered 'undruggable' by traditional small molecules. Advances in cyclization techniques, including biotechnological and regioselective methods, have enabled rapid and efficient synthesis of these cyclopeptides, enhancing their potential as therapeutic agents.","whyItMatters":"Targeting PPIs is crucial for developing new treatments for diseases like cancer, but these interactions are often difficult to inhibit with small molecules. Synthetic cyclopeptides provide a novel approach to overcome this challenge, potentially leading to new therapies.","specificNumbers":"","methodology":"This is a review article summarizing recent advances in the design, synthesis, and application of synthetic cyclopeptides targeting PPIs. It covers structural investigations identifying key motifs, synthetic strategies for peptide cyclization, and examples of therapeutic macrocycles.","limitations":"As a review, the article does not present new experimental data and the effectiveness of synthetic cyclopeptides depends on further clinical validation. The complexity of synthesis and delivery challenges remain significant hurdles."},{"rthcId":"RPEP-03103","title":"Characterization of Substance P processing in mouse spinal cord S9 fractions using high-resolution Quadrupole-Orbitrap mass spectrometry.","authors":"Saidi, Mouna; Kamali, Soufiane; Beaudry, Francis","year":2016,"journal":"Neuropeptides, 59, 47-55","doi":"10.1016/j.npep.2016.06.002","pmid":"27344070","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Proteolysis regulates extracellular Substance P concentrations in the mouse spinal cord by generating active C-terminal fragments such as SP3-11, SP5-11, and SP8-11, which retain affinity for the Neurokinin 1 receptor. The metabolic half-life of Substance P is short (3.5 min), whereas its C-terminal fragments exhibit significantly greater stability. Prolyl endopeptidase is implicated in the N-terminal processing of Substance P, as shown by inhibitor studies reducing fragment formation.","whyItMatters":"Understanding how Substance P is metabolized helps clarify mechanisms controlling pain and inflammation signaling. This knowledge could guide development of therapies targeting peptide processing enzymes to modulate pain responses.","specificNumbers":"","methodology":"High-resolution Quadrupole-Orbitrap mass spectrometry was used to characterize and quantify Substance P and its fragments in mouse spinal cord S9 fractions. The metabolic stability of peptides was measured, and specific enzyme inhibitors were applied to assess the role of Prolyl endopeptidase in Substance P processing.","limitations":"The study was conducted in vitro using mouse spinal cord fractions, which may not fully replicate in vivo conditions. The exact physiological relevance of the identified fragments and enzyme activity requires further in vivo validation."},{"rthcId":"RPEP-03104","title":"Role of peptide YY in 5-fluorouracil-induced reduction of dietary intake.","authors":"Sakai, Hiroyasu; Kai, Yuki; Takase, Kazuhide; Sato, Ken; Kimura, Minami; Tabata, Shoko; Yaegashi, Miyabi; Sato, Fumiaki; Yomoto, Tetsuro; Narita, Minoru","year":2016,"journal":"Clinical and experimental pharmacology & physiology, 43(8), 753-9","doi":"10.1111/1440-1681.12588","pmid":"27130783","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"5-fluorouracil treatment in mice increased expression and serum levels of peptide YY (PYY) and glucagon-like peptide-1 (GLP-1). The reduction in food intake caused by 5-FU was significantly attenuated by blocking the neuropeptide Y type 2 (NPY2) receptor, which mediates PYY signaling, but not by blocking the GLP-1 receptor.","whyItMatters":"Understanding how gut hormones like PYY contribute to chemotherapy-induced appetite loss can help develop treatments to prevent weight loss and improve quality of life for cancer patients.","specificNumbers":"","methodology":"Mice received daily intraperitoneal injections of 5-fluorouracil (50 mg/kg) for four days. Gene expression of PYY and proglucagon was measured in the colon by RT-PCR, and serum levels of PYY and GLP-1 were assessed by ELISA. Some mice were pretreated with receptor antagonists for GLP-1 or NPY2 receptors before 5-FU administration to evaluate effects on food intake.","limitations":"The study was conducted in mice, so results may not fully translate to humans. The exact mechanisms by which PYY influences appetite during chemotherapy require further investigation."},{"rthcId":"RPEP-03105","title":"Hepcidin, Cathelicidin-1 and IL-8 as immunological markers of responsiveness in early developmental stages of rainbow trout.","authors":"Santana, Paula A; Guzmán, Fanny; Forero, Juan C; Luna, Omar F; Mercado, Luis","year":2016,"journal":"Developmental and comparative immunology, 62, 48-57","doi":"10.1016/j.dci.2016.04.014","pmid":"27106706","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Hepcidin and cathelicidin-1 gene expression was detected only at 34 and 42 days post hatching, while IL-8 expression persisted from 34 to 66 days. Immunofluorescence indicated that skin, gills, and intestine tissues actively respond to LPS challenge, highlighting these as key sites of immune activity in early trout development.","whyItMatters":"Understanding when and where immune responses develop in young fish can help improve disease management in aquaculture, reducing mortality and economic losses. Identifying reliable immune markers may guide health monitoring and vaccine development.","specificNumbers":"","methodology":"The study exposed rainbow trout fry at 34, 42, 56, and 66 days post hatching to lipopolysaccharide (LPS) from Pseudomonas aeruginosa for 8 hours. RNA was extracted to assess gene expression of immune markers, and polyclonal antibodies were generated to detect protein expression via immunofluorescence in various tissues.","limitations":"The study did not specify sample sizes or provide quantitative measures of immune response strength. The exact functional impact of these markers on disease resistance was not assessed."},{"rthcId":"RPEP-03106","title":"Oral Administration of Peptide-Based Drugs: Beyond Lipinski's Rule.","authors":"Santos, Gabriela B; Ganesan, A; Emery, Flavio S","year":2016,"journal":"ChemMedChem, 11(20), 2245-2251","doi":"10.1002/cmdc.201600288","pmid":"27596610","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The analysis revealed that the majority of orally administered peptide drugs possess linear structures, challenging the prevailing assumption that cyclic peptides have superior oral bioavailability. Structural and physicochemical properties vary between cyclic and linear peptides, but oral availability is not exclusive to cyclic forms.","whyItMatters":"Understanding which peptide structures are more likely to be effective when taken orally can guide the design of new peptide drugs with improved absorption and therapeutic potential.","specificNumbers":"","methodology":"An extensive analysis was conducted on all known peptide drugs and clinical candidates, examining their peptide features, physicochemical and structural properties, and correlating these with administration routes and therapeutic classes.","limitations":"The study does not specify the exact study type or provide quantitative measures of evidence strength, limiting the ability to assess the robustness of conclusions."},{"rthcId":"RPEP-03107","title":"Neuropeptide Y (NPY) and posttraumatic stress disorder (PTSD): A translational update.","authors":"Schmeltzer, Sarah N; Herman, James P; Sah, Renu","year":2016,"journal":"Experimental neurology, 284(Pt B), 196-210","doi":"10.1016/j.expneurol.2016.06.020","pmid":"27377319","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review consolidates multiple lines of evidence linking NPY to PTSD:\n\n- NPY is abundantly expressed in forebrain limbic and brainstem areas that regulate stress and emotional behaviors\n- Animal studies demonstrate NPY's role in stress responses, anxiety, fear, and autonomic regulation\n- Genetic studies associate NPY polymorphisms with stress coping and affect\n- CSF measurements in combat veterans provide direct evidence: reduced NPY associates with PTSD diagnosis and symptomology\n- NPY is also involved in pain, depression, addiction, and metabolism — all PTSD comorbidities\n- The NPY system represents both a biomarker for PTSD risk/diagnosis and a potential therapeutic target","whyItMatters":"PTSD affects millions of people worldwide, and current treatments are only partially effective. Understanding that a specific neuropeptide — NPY — is linked to both PTSD resilience and vulnerability opens new therapeutic avenues. If NPY levels could be enhanced in vulnerable individuals, it might prevent PTSD or improve treatment outcomes. The CSF data from combat veterans provides some of the most compelling human evidence.","specificNumbers":"","methodology":"Narrative review consolidating preclinical animal studies, clinical genetic studies, and translational research including cerebrospinal fluid NPY measurements in combat veterans. The review covers NPY's role in stress regulation, anxiety, fear conditioning, and autonomic function as they relate to PTSD.","limitations":"As a review, no original data is presented. The causal relationship between NPY levels and PTSD has not been definitively established — low NPY could be a consequence rather than a cause of PTSD. No NPY-based treatments for PTSD have been clinically validated. Intranasal NPY administration has been explored but not proven effective in large trials. The complexity of PTSD (genetic, environmental, psychological factors) means NPY is likely one of many contributing factors."},{"rthcId":"RPEP-03108","title":"The immediate effect of traditional Malay massage on substance P, inflammatory mediators, pain scale and functional outcome among patients with low back pain: study protocol of a randomised controlled trial.","authors":"Sejari, Nurhanisah; Kamaruddin, Kamaria; Ramasamy, Kalavathy; Lim, Siong Meng; Neoh, Chin Fen; Ming, Long Chiau","year":2016,"journal":"BMC complementary and alternative medicine, 16, 16","doi":"10.1186/s12906-016-0988-1","pmid":"26767971","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"This randomized controlled trial aims to determine the immediate effects of traditional Malay massage on substance P levels, inflammatory mediators, pain intensity, and functional outcomes in patients with low back pain. It hypothesizes that the massage will reduce substance P and inflammatory markers, thereby decreasing pain and improving function.","whyItMatters":"Understanding how traditional Malay massage affects pain-related chemicals and inflammation could validate its use as a complementary therapy for low back pain and guide more effective pain management strategies.","specificNumbers":"","methodology":"A total of 66 patients with low back pain will be randomly assigned to either a traditional Malay massage group or a control group receiving a relaxation position. Blood and saliva samples will be collected before and immediately after the intervention to measure substance P and inflammatory mediators. Pain intensity and functional disability will also be assessed using validated scales.","limitations":"The study is non-blinded, which may introduce bias, and only measures immediate effects without assessing long-term benefits. The sample size is moderate, which may limit generalizability."},{"rthcId":"RPEP-03109","title":"The amyloid hypothesis of Alzheimer's disease at 25 years.","authors":"Selkoe, Dennis J; Hardy, John","year":2016,"journal":"EMBO molecular medicine, 8(6), 595-608","doi":"10.15252/emmm.201606210","pmid":"27025652","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03110","title":"Analytical Issues with Natriuretic Peptides - has this been Overly Simplified?","authors":"Semenov, Alexander G; Katrukha, Alexey G","year":2016,"journal":"EJIFCC, 27(3), 189-207","doi":null,"pmid":"27683533","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Despite more than two decades of clinical use, our understanding of natriuretic peptide biochemistry remains incomplete. The circulating forms of natriuretic peptides are far more diverse than initially appreciated, with multiple molecular forms coexisting in plasma. This complexity means that different assays may measure different combinations of these forms, potentially giving inconsistent results.\n\nThe simplistic clinical model — that elevated NP values directly indicate heart failure severity and predict prognosis — is insufficient. A deeper understanding of how the NP system works, including the processing, degradation, and clearance of different peptide forms, is needed for correct interpretation of results in cardiovascular practice.","whyItMatters":"Natriuretic peptide tests are among the most commonly ordered cardiac biomarkers worldwide, used daily in emergency departments and cardiology clinics. If these tests are being interpreted too simplistically — or if different assays are measuring different molecular forms — patients could receive incorrect diagnoses or inappropriate treatment decisions. Understanding these analytical nuances is essential for improving cardiac care.","specificNumbers":"","methodology":"Narrative review summarizing recent advances in understanding the biochemistry of the natriuretic peptide system, the diversity of circulating peptide forms, and the analytical challenges these present for clinical assays. The review integrates findings from biochemical, clinical, and analytical studies.","limitations":"This is a narrative review without new experimental data. The authors rely on previously published studies with varying methodologies. The review was published in 2016, and some analytical issues may have been addressed by newer assay platforms. Specific recommendations for improved testing are limited."},{"rthcId":"RPEP-03111","title":"Is there an effect of ghrelin/ghrelin analogs on cancer? A systematic review.","authors":"Sever, Sakine; White, Donna L; Garcia, José M","year":2016,"journal":"Endocrine-related cancer, 23(9), R393-409","doi":"10.1530/ERC-16-0130","pmid":"27552970","tags":["ghrelin","cancer","cachexia"],"studyType":"Systematic Review","evidenceStrength":"Moderate","keyFinding":"This systematic review examined 61 in vivo studies on ghrelin, ghrelin-receptor agonists, and ghrelin genetic variants in relation to cancer. Nearly three-quarters (73.8%) of studies found either no statistically significant association or an inverse association between ghrelin and cancer risk, presence, or growth.\n\nNotably, all 11 studies that specifically tested treatment with exogenous ghrelin or ghrelin-receptor agonists reported null or inverse cancer associations. Only 16.7% of all reviewed studies found a positive association, and 10% reported mixed results. Cancer patients tended to have lower serum ghrelin levels than controls for some cancer types, though not all.","whyItMatters":"Ghrelin-based therapies are being developed to treat cancer cachexia — the severe muscle wasting and weight loss that affects many cancer patients and worsens survival. A major safety concern has been whether stimulating the ghrelin pathway could promote cancer growth. This systematic review provides reassurance that the majority of evidence points toward ghrelin being safe or even protective in cancer contexts, clearing a key hurdle for using these therapies in patients who desperately need them.","specificNumbers":"61 studies reviewed · 73.8% null or inverse association · 16.7% positive association · 10% mixed · all 11 exogenous treatment studies showed no cancer-promoting effect","methodology":"The authors performed a systematic review by searching PubMed with structured queries and supplementing with reference list screening from related reviews and meta-analyses. They identified peer-reviewed original research studies — both human and animal — that investigated ghrelin, ghrelin-receptor agonists, or ghrelin genetic variants in relation to cancer risk, cancer presence, or tumor growth. Studies were categorized by whether they found positive, null, inverse, or mixed associations.","limitations":"The review included studies with widely varying designs, cancer types, and populations, making direct comparisons difficult. Many included studies were observational and could not establish causation. The review was limited to PubMed searches and may have missed relevant studies in other databases. Most exogenous ghrelin treatment studies were short-term, so long-term cancer effects remain unclear."},{"rthcId":"RPEP-03112","title":"Archetypal tryptophan-rich antimicrobial peptides: properties and applications.","authors":"Shagaghi, Nadin; Palombo, Enzo A; Clayton, Andrew H A; Bhave, Mrinal","year":2016,"journal":"World journal of microbiology & biotechnology, 32(2), 31","doi":"10.1007/s11274-015-1986-z","pmid":"26748808","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tryptophan-rich antimicrobial peptides (TRPs) such as indolicidin, tritrpticin, and lactoferricin exhibit potent broad-spectrum antimicrobial activity. Their unique ability to insert into and cross microbial membranes without destroying them suggests novel mechanisms involving intracellular targets like nucleic acids and enzymes.","whyItMatters":"Understanding TRPs expands options for developing new antimicrobial agents against drug-resistant pathogens, addressing a critical global health challenge.","specificNumbers":"","methodology":"This study is a literature overview summarizing biochemical properties, structures, antimicrobial activities, mechanistic insights, and applications of archetypal tryptophan-rich peptides derived from natural sources.","limitations":"The study is a review and does not provide new experimental data; the clinical efficacy and safety of TRPs require further investigation."},{"rthcId":"RPEP-03113","title":"Membrane Core-Specific Antimicrobial Action of Cathelicidin LL-37 Peptide Switches Between Pore and Nanofibre Formation.","authors":"Shahmiri, Mahdi; Enciso, Marta; Adda, Christopher G; Smith, Brian J; Perugini, Matthew A; Mechler, Adam","year":2016,"journal":"Scientific reports, 6, 38184","doi":"10.1038/srep38184","pmid":"27901075","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03114","title":"Mitigating Meal-Related Glycemic Excursions in an Insulin-Sparing Manner During Closed-Loop Insulin Delivery: The Beneficial Effects of Adjunctive Pramlintide and Liraglutide.","authors":"Sherr, Jennifer L; Patel, Neha S; Michaud, Camille I; Palau-Collazo, Miladys M; Van Name, Michelle A; Tamborlane, William V; Cengiz, Eda; Carria, Lori R; Tichy, Eileen M; Weinzimer, Stuart A","year":2016,"journal":"Diabetes care, 39(7), 1127-34","doi":"10.2337/dc16-0089","pmid":"27208332","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Adjunctive pramlintide significantly delayed peak postprandial plasma glucose and reduced glucose excursions and incremental glucose area under the curve during closed-loop insulin delivery. Liraglutide also reduced glucose excursions and incremental glucose AUC, decreased prandial and total daily insulin doses by approximately 26-28%, and induced a mean weight loss of 3.2 kg over 3-4 weeks.","whyItMatters":"Improving post-meal blood sugar control without increasing insulin doses can reduce diabetes complications and improve quality of life. These adjunctive therapies offer a promising insulin-sparing approach to enhance closed-loop insulin delivery systems.","specificNumbers":"","methodology":"Two outpatient studies were conducted with young adults with type 1 diabetes using closed-loop insulin delivery. Subjects underwent 3-4 weeks of dose escalation of either pramlintide (60 μg/meal) or liraglutide (1.8 mg daily), followed by two 24-hour sessions comparing closed-loop alone versus closed-loop plus adjunctive therapy. Meals were standardized and unannounced during sessions to assess postprandial glucose control.","limitations":"The sample sizes were small and limited to young adults with relatively well-controlled type 1 diabetes. The short duration (3-4 weeks) limits understanding of long-term effects and safety. Larger, longer-term studies are needed."},{"rthcId":"RPEP-03115","title":"Effects of intraplantar botulinum toxin-B on carrageenan-induced changes in nociception and spinal phosphorylation of GluA1 and Akt.","authors":"Sikandar, Shafaq; Gustavsson, Ynette; Marino, Marc J; Dickenson, Anthony H; Yaksh, Tony L; Sorkin, Linda S; Ramachandran, Roshni","year":2016,"journal":"The European journal of neuroscience, 44(1), 1714-22","doi":"10.1111/ejn.13261","pmid":"27108664","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Intraplantar BoNT-B (1 U) reduced carrageenan-induced mechanical allodynia without affecting paw edema, confirming a central rather than local anti-inflammatory mechanism. The toxin decreased spinal phosphorylation of GluA1 (glutamate receptor subunit) at serine 845 and Akt at serine 473, as well as c-Fos expression — all markers of spinal nociceptive facilitation. BoNT-B inhibited NMDA-evoked but not substance P-evoked phosphorylation of GluA1 and Akt in the dorsal horn, demonstrating selective modulation of glutamate-mediated versus tachykinin-mediated spinal pain pathways.","whyItMatters":"Chronic inflammatory pain is a massive clinical burden, and current treatments (NSAIDs, opioids) have significant side effects. Botulinum toxin is already FDA-approved for chronic migraine, and understanding its spinal mechanism of action could expand its use to other pain conditions. The selective blockade of NMDA-mediated (but not substance P-mediated) spinal pain pathways suggests botulinum toxin acts on specific aspects of central sensitization — the process by which the spinal cord amplifies pain signals.","specificNumbers":"","methodology":"Male C57BL/6 mice received unilateral intraplantar BoNT-B (1 U, 30 μL) or saline followed by intraplantar carrageenan (2%) to induce inflammation. Additional groups received intrathecal NMDA or substance P to probe specific spinal pathways. Outcomes included mechanical allodynia (behavioral), paw edema, and spinal dorsal horn biochemistry (pGluA1, pAkt, c-Fos immunostaining via Western blot and immunohistochemistry).","limitations":"Only male mice were studied, and sex differences in pain processing are well-documented. The study does not directly visualize or trace BoNT-B transport from the foot to the spinal cord. The 1 U dose may not be directly translatable to human dosing. The carrageenan model represents acute inflammatory pain; whether BoNT-B has similar effects in chronic pain models is unknown. The selective blockade of NMDA versus substance P pathways may reflect dose or timing rather than absolute selectivity."},{"rthcId":"RPEP-03116","title":"Brain-gut Axis and Pentadecapeptide BPC 157: Theoretical and Practical Implications.","authors":"Sikiric, Predrag; Seiwerth, Sven; Rucman, Rudolf; Kolenc, Danijela; Vuletic, Lovorka Batelja; Drmic, Domagoj; Grgic, Tihomir; Strbe, Sanja; Zukanovic, Goran; Crvenkovic, Dalibor; Madzarac, Goran; Rukavina, Iva; Sucic, Mario; Baric, Marko; Starcevic, Neven; Krstonijevic, Zoran; Bencic, Martina Lovric; Filipcic, Igor; Rokotov, Dinko Stancic; Vlainic, Josipa","year":2016,"journal":"Current neuropharmacology, 14(8), 857-865","doi":null,"pmid":"27138887","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BPC 157 exhibits strong cytoprotective and healing properties in the gastrointestinal tract and demonstrates neuroprotective effects in multiple central nervous system injury models. It modulates serotonergic and dopaminergic neurotransmission and promotes nerve regeneration and functional recovery in animal studies.","whyItMatters":"BPC 157’s dual action on gut and brain health highlights its potential as a novel therapeutic agent for complex disorders involving both systems, which are often difficult to treat effectively.","specificNumbers":"","methodology":"This article is a review summarizing experimental research on BPC 157’s effects on the brain-gut axis, including animal models of gastrointestinal lesions, nerve injury, and central nervous system disorders.","limitations":"The findings are primarily based on animal studies and preclinical models; clinical efficacy and safety in humans require further investigation."},{"rthcId":"RPEP-03117","title":"Altered secondary structure of Dynorphin A associates with loss of opioid signalling and NMDA-mediated excitotoxicity in SCA23.","authors":"Smeets, Cleo J L M; Zmorzyńska, Justyna; Melo, Manuel N; Stargardt, Anita; Dooley, Colette; Bakalkin, Georgy; McLaughlin, Jay; Sinke, Richard J; Marrink, Siewert-Jan; Reits, Eric; Verbeek, Dineke S","year":2016,"journal":"Human molecular genetics, 25(13), 2728-2737","doi":null,"pmid":"27260403","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"SCA23 mutations in Dynorphin A disrupted the peptide's N-terminal α-helix, a key structural feature needed for κ-opioid receptor binding. This structural change led to decreased opioid receptor affinity.\n\nThe R6W and R9C mutations made Dynorphin A markedly resistant to degradation and less soluble, leading to peptide accumulation. R6W and wild-type Dynorphin A were the most toxic to primary cerebellar neurons. For R6W Dynorphin A, this toxicity involved a switch from opioid to NMDA receptor signaling, while wild-type toxicity occurred through a different mechanism. L5S Dynorphin A showed the opposite pattern — increased degradation and no aggregation.\n\nThe authors propose that SCA23 pathology results from two converging mechanisms: loss of opioid-mediated neuroprotection and gain of NMDA-mediated excitotoxicity.","whyItMatters":"This study reveals a clear molecular mechanism for how a single peptide mutation can cause neurodegeneration — by simultaneously removing a protective signal and creating a toxic one. Understanding this dual mechanism opens potential therapeutic strategies: either restoring opioid signaling, blocking NMDA-mediated excitotoxicity, or preventing mutant peptide accumulation.","specificNumbers":"","methodology":"Researchers used molecular dynamics simulations to model how SCA23 mutations affect Dynorphin A's secondary structure. They tested mutant peptides for κ-opioid receptor binding affinity, degradation resistance, solubility, and aggregation properties. Neurotoxicity was assessed using primary cerebellar neuron cultures from mice, with analysis of opioid versus NMDA receptor-mediated signaling pathways.","limitations":"The study was conducted entirely in vitro and in cell culture, without in vivo validation in animal models. Sample sizes for cell culture experiments were not specified in the abstract. The clinical relevance of the findings needs confirmation in patient-derived tissues or animal models of SCA23. The study focused on a rare disease, which limits the patient population where findings could be directly applied."},{"rthcId":"RPEP-03118","title":"The importance of Pharmacovigilance for the drug safety: Focus on cardiovascular profile of incretin-based therapy.","authors":"Sportiello, Liberata; Rafaniello, Concetta; Scavone, Cristina; Vitale, Cristiana; Rossi, Francesco; Capuano, Annalisa","year":2016,"journal":"International journal of cardiology, 202, 731-5","doi":"10.1016/j.ijcard.2015.10.002","pmid":"26461922","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Incretin-based therapies, including GLP-1 receptor agonists and DPP-4 inhibitors, initially showed good tolerability but post-marketing data have raised concerns about cardiovascular risks, including heart failure requiring hospitalization, as well as infections and pancreatitis. Regulatory agencies have noted these risks but evidence remains controversial.","whyItMatters":"Understanding the long-term safety of incretin-based drugs is crucial for protecting patients with diabetes from potential heart complications and other serious side effects. Pharmacovigilance helps ensure these drugs remain safe as their use expands.","specificNumbers":"","methodology":"This is a review article summarizing recent European Pharmacovigilance legislation and analyzing current literature and regulatory opinions on the safety profile of incretin-based diabetes therapies, with a focus on cardiovascular risks.","limitations":"The article is a review without new experimental data; evidence on cardiovascular and cancer risks remains inconclusive and controversial, requiring further research."},{"rthcId":"RPEP-03119","title":"Lateral hypothalamic melanocortin receptor signaling modulates binge-like ethanol drinking in C57BL/6J mice.","authors":"Sprow, Gretchen M; Rinker, Jennifer A; Lowery-Gointa, Emily G; Sparrow, Angela M; Navarro, Montserrat; Thiele, Todd E","year":2016,"journal":"Addiction biology, 21(4), 835-46","doi":"10.1111/adb.12264","pmid":"25975524","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Repeated binge-like ethanol drinking produced specific changes in melanocortin peptide expression in hypothalamic subregions: α-MSH (the appetite-suppressing peptide) was selectively decreased, while AgRP (the appetite-stimulating peptide) was selectively increased. These changes were specific to ethanol — not seen with sucrose or water controls.\n\nFunctional manipulation confirmed the significance: injection of the nonselective melanocortin receptor agonist melanotan-II (MTII) directly into the lateral hypothalamus (LH) significantly reduced binge-like ethanol consumption, while injection of the antagonist AgRP into the same region augmented drinking. These effects were region-specific to the LH, as they were not observed when drugs were delivered to other brain regions.","whyItMatters":"Binge drinking affects approximately 26% of US adults and is linked to liver disease, cardiovascular problems, and accidental death. Current treatments for alcohol use disorder (naltrexone, acamprosate, disulfiram) have limited effectiveness, and binge drinking specifically has no approved targeted therapy. The melanocortin system — which regulates both feeding and reward — represents a novel therapeutic target. The fact that a peptide drug (melanotan-II) reduced binge drinking in a specific brain region opens the door to developing targeted peptide or small-molecule melanocortin therapies for alcohol abuse.","specificNumbers":"","methodology":"Male C57BL/6J mice underwent 1, 3, or 6 cycles of the 'drinking in the dark' (DID) binge drinking protocol with ethanol, sucrose, or water. Brain tissue was processed by immunohistochemistry for α-MSH and AgRP expression in hypothalamic subregions. Site-directed microinjection was used to deliver melanotan-II (MCR agonist) or AgRP (MCR antagonist) into the lateral hypothalamus, and subsequent ethanol consumption was measured.","limitations":"Only male mice were studied — sex differences in melanocortin signaling and alcohol consumption are well-documented. The nonselective MCR agonist MTII activates multiple receptor subtypes (MC3R and MC4R), so the specific receptor mediating the anti-drinking effect is unknown. Intracerebral drug delivery is not clinically practical; systemic peptide delivery or small-molecule MCR agonists would be needed for human treatment. The DID model, while validated, captures only one pattern of problematic drinking. Long-term effects and potential for tolerance were not assessed."},{"rthcId":"RPEP-03120","title":"BPC 157: The counteraction of succinylcholine, hyperkalemia, and arrhythmias.","authors":"Stambolija, Vasilije; Stambolija, Tamara Perleta; Holjevac, Jadranka Katancic; Murselovic, Tamara; Radonic, Jelena; Duzel, Viktor; Duplancic, Bozidar; Uzun, Sandra; Zivanovic-Posilovic, Gordana; Kolenc, Danijela; Drmic, Domagoj; Romic, Zeljko; Seiwerth, Sven; Sikiric, Predrag","year":2016,"journal":"European journal of pharmacology, 781, 83-91","doi":"10.1016/j.ejphar.2016.04.004","pmid":"27060013","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BPC 157 at both 10 µg/kg and 10 ng/kg doses completely eliminated succinylcholine-induced hyperkalemia and cardiac arrhythmias in rats. It also markedly attenuated or eliminated behavioral agitation, muscle twitches, motionless resting, and post-succinylcholine hyperalgesia (pain sensitivity).\n\nBPC 157 immediately eliminated leg contractures and counteracted both edema and the decrease in muscle fibers in the diaphragm and tibial muscles. These protective effects were seen whether BPC 157 was given intraperitoneally 30 minutes before succinylcholine, immediately after, or orally in drinking water for 24 hours prior to succinylcholine administration.","whyItMatters":"Succinylcholine-induced hyperkalemia is a potentially fatal complication during anesthesia. Having a peptide that can prevent or reverse these effects — especially one effective orally — could be clinically significant. This also adds to the growing body of BPC 157 research showing protective effects across multiple organ systems.","specificNumbers":"","methodology":"Rats received succinylcholine (1.0 mg/kg) injected into the right anterior tibial muscle. BPC 157 was administered via three routes: intraperitoneal injection 30 minutes before succinylcholine, intraperitoneal injection immediately after, or orally in drinking water for 24 hours before. Assessments were conducted at 3 min, 30 min, 1 day, 3 days, 5 days, and 7 days post-succinylcholine, evaluating muscle function, serum enzymes, potassium levels, cardiac rhythm, and behavioral outcomes.","limitations":"This was conducted entirely in rats, and the results have not been replicated in humans. The exact molecular mechanism by which BPC 157 counteracts succinylcholine's effects was not elucidated. The study comes from a research group that publishes extensively on BPC 157, and independent replication by other laboratories would strengthen the evidence. No human pharmacokinetic data exists for BPC 157."},{"rthcId":"RPEP-03121","title":"Gastrin-releasing Peptide Receptor Imaging in Breast Cancer Using the Receptor Antagonist (68)Ga-RM2 And PET.","authors":"Stoykow, Christian; Erbes, Thalia; Maecke, Helmut R; Bulla, Stefan; Bartholomä, Mark; Mayer, Sebastian; Drendel, Vanessa; Bronsert, Peter; Werner, Martin; Gitsch, Gerald; Weber, Wolfgang A; Stickeler, Elmar; Meyer, Philipp T","year":2016,"journal":"Theranostics, 6(10), 1641-50","doi":"10.7150/thno.14958","pmid":"27446498","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03122","title":"Genetic variation of the growth hormone secretagogue receptor gene is associated with alcohol use disorders identification test scores and smoking.","authors":"Suchankova, Petra; Nilsson, Staffan; von der Pahlen, Bettina; Santtila, Pekka; Sandnabba, Kenneth; Johansson, Ada; Jern, Patrick; Engel, Jörgen A; Jerlhag, Elisabet","year":2016,"journal":"Addiction biology, 21(2), 481-8","doi":"10.1111/adb.12277","pmid":"26059200","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The minor allele of the rs2948694 SNP in the ghrelin receptor gene (GHSR) was associated with higher AUDIT scores (P = 0.0204, recessive model) and smoking (P = 0.0002, dominant model) in 4,161 Finnish adults. Post hoc analysis showed this risk allele was also associated with increased likelihood of high-level alcohol problems (AUDIT scores ≥ 16; P = 0.0043, recessive model).\n\nTwo SNPs in the pre-proghrelin gene (GHRL) — rs4684677 (Gln90Leu) and rs696217 (Leu72Met) — were not significantly associated with alcohol use or smoking outcomes.","whyItMatters":"Addiction has a strong hereditary component, and understanding which genes contribute to risk can help identify new therapeutic targets. Ghrelin is a peptide already known to influence reward and motivation in animal models. This study provides human genetic evidence supporting the same connection, suggesting that drugs targeting the ghrelin receptor — some of which are already in development — could potentially be repurposed for treating alcohol and nicotine addiction.","specificNumbers":"","methodology":"Researchers genotyped three single nucleotide polymorphisms (SNPs) — two in the ghrelin gene (GHRL) and one in the ghrelin receptor gene (GHSR) — in 4,161 individuals from a Finnish population-based cohort (the Genetics of Sexuality and Aggression project). Alcohol use was measured using the AUDIT (Alcohol Use Disorders Identification Test) questionnaire. Associations with AUDIT scores were tested using linear regression, and associations with smoking were tested using logistic regression.","limitations":"This is an observational genetic association study and cannot prove that the GHSR variant causes higher alcohol use or smoking. The association with AUDIT scores was nominally significant (P = 0.0204), which may not survive correction for multiple comparisons. The cohort was entirely Finnish, limiting generalizability to other populations. AUDIT is a self-report questionnaire, which may underestimate actual alcohol consumption. Replication in independent cohorts is needed."},{"rthcId":"RPEP-03123","title":"The Roles of Cathelicidin LL-37 in Inflammatory Bowel Disease.","authors":"Sun, Lihua; Wang, Wensheng; Xiao, Weidong; Yang, Hua","year":2016,"journal":"Inflammatory bowel diseases, 22(8), 1986-91","doi":"10.1097/MIB.0000000000000804","pmid":"27135484","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03124","title":"Purification of Antioxidant Peptides by High Resolution Mass Spectrometry from Simulated Gastrointestinal Digestion Hydrolysates of Alaska Pollock (Theragra chalcogramma) Skin Collagen.","authors":"Sun, Liping; Chang, Weidan; Ma, Qingyu; Zhuang, Yongliang","year":2016,"journal":"Marine drugs, 14(10)","doi":null,"pmid":"27763502","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Four antioxidant peptides (YGCC, DSSCSG, NNAEYYK, PAGNVR) were identified from simulated gastrointestinal digestion hydrolysates of Alaska pollock skin collagen using LC-ESI-LTQ-Orbitrap-MS combined with de novo and UniProt software. These peptides exhibited significant hydroxyl radical scavenging activity.","whyItMatters":"Identifying antioxidant peptides from marine collagen could lead to natural antioxidant supplements or functional foods that support health by reducing oxidative stress.","specificNumbers":"","methodology":"Alaska pollock skin collagen was hydrolyzed using alcalase and subjected to two rounds of simulated gastrointestinal digestion. Antioxidant activities were measured in vitro, and peptides were purified and identified using high-resolution mass spectrometry and bioinformatics software.","limitations":"The study did not include in vivo testing to confirm antioxidant effects in living organisms, and the exact bioavailability of identified peptides remains unknown."},{"rthcId":"RPEP-03125","title":"Vitamin D-induced up-regulation of human keratinocyte cathelicidin anti-microbial peptide expression involves retinoid X receptor α.","authors":"Svensson, Daniel; Nebel, Daniel; Voss, Ulrikke; Ekblad, Eva; Nilsson, Bengt-Olof","year":2016,"journal":"Cell and tissue research, 366(2), 353-362","doi":"10.1007/s00441-016-2449-z","pmid":"27357804","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"1α,25-dihydroxyvitamin D3 (1,25D3) significantly upregulates the CAMP gene and LL-37 protein expression in human keratinocytes, and this effect requires retinoid X receptor alpha (RXRα) but is independent of vitamin D receptor (VDR) upregulation.","whyItMatters":"Understanding how vitamin D regulates antimicrobial peptides via RXRα can inform new strategies to boost skin immunity and develop treatments for infections or skin disorders.","specificNumbers":"","methodology":"The study analyzed gene and protein expression in human skin and gingival biopsies and in cultured human keratinocyte (HaCaT) cells treated with 1,25D3. RXRα involvement was tested using short interfering RNA to knock down RXRα expression.","limitations":"The study was conducted primarily in cell cultures and tissue biopsies, which may not fully replicate in vivo skin conditions; the exact signaling pathways downstream of RXRα were not fully elucidated."},{"rthcId":"RPEP-03126","title":"Substance P Enhances Keratocyte Migration and Neutrophil Recruitment through Interleukin-8.","authors":"Słoniecka, Marta; Le Roux, Sandrine; Zhou, Qingjun; Danielson, Patrik","year":2016,"journal":"Molecular pharmacology, 89(2), 215-25","doi":"10.1124/mol.115.101014","pmid":"26646648","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Substance P expression and secretion increase in human keratocytes after injury, enhancing their migration via actin cytoskeleton reorganization and focal adhesion formation through PI3K and Rac1/RhoA pathways. Substance P also upregulates IL-8 expression, which contributes to keratocyte migration and neutrophil recruitment, mediated by the neurokinin-1 receptor.","whyItMatters":"Understanding how substance P promotes keratocyte migration and immune cell recruitment provides insight into corneal wound healing mechanisms, potentially guiding new treatments to prevent scarring and blindness.","specificNumbers":"","methodology":"The study used in vitro injury models of human keratocytes to analyze substance P expression and secretion. Cellular migration assays, molecular pathway analyses, and cytokine expression measurements were performed to elucidate the mechanisms by which substance P influences keratocyte behavior and neutrophil attraction.","limitations":"The study was conducted in vitro, limiting direct conclusions about in vivo corneal healing. The exact in vivo relevance and therapeutic potential require further investigation."},{"rthcId":"RPEP-03127","title":"A potential contribution of antimicrobial peptide LL-37 to tissue fibrosis and vasculopathy in systemic sclerosis.","authors":"Takahashi, T; Asano, Y; Nakamura, K; Yamashita, T; Saigusa, R; Ichimura, Y; Toyama, T; Taniguchi, T; Yoshizaki, A; Tamaki, Z; Tada, Y; Sugaya, M; Kadono, T; Sato, S","year":2016,"journal":"The British journal of dermatology, 175(6), 1195-1203","doi":"10.1111/bjd.14699","pmid":"27105895","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"LL-37, the human antimicrobial peptide known primarily for fighting infections, was found to be significantly overexpressed in the skin of systemic sclerosis (SSc) patients — particularly in the small blood vessels of affected skin. Serum LL-37 levels were significantly higher in SSc patients than in healthy controls, and these levels correlated positively with skin fibrosis severity (skin score), alveolitis activity (lung inflammation), and the presence of digital ulcers. The study identified a molecular mechanism: deficiency of the transcription factor Fli1 drives LL-37 upregulation in endothelial cells, confirmed through gene silencing and chromatin immunoprecipitation. Mouse models of SSc (bleomycin-treated and Fli1+/- mice) showed similar upregulation of CRAMP, the mouse equivalent of LL-37.","whyItMatters":"Systemic sclerosis is a devastating autoimmune disease with limited treatment options, characterized by progressive skin fibrosis, blood vessel damage, and organ involvement. This study reveals that LL-37 — normally a protective antimicrobial peptide — may actually contribute to the disease process. Understanding this dual role could open new therapeutic strategies, potentially by modulating LL-37 levels to reduce fibrosis and vascular damage in SSc.","specificNumbers":"","methodology":"Combined human and mouse study. In human SSc skin, LL-37 expression was evaluated by immunostaining and quantitative RT-PCR. Serum LL-37 levels were measured by ELISA in SSc patients and healthy controls. Mechanistic studies used gene silencing and chromatin immunoprecipitation in human dermal microvascular endothelial cells to examine Fli1's regulation of the LL-37 gene (CAMP). Two mouse models were used: bleomycin-induced skin fibrosis and Fli1 heterozygous knockout mice.","limitations":"While the study demonstrates strong correlations between LL-37 levels and disease severity, it does not prove that LL-37 directly causes fibrosis or vascular damage. The exact downstream mechanisms by which elevated LL-37 contributes to tissue pathology remain unclear. Sample sizes for the human serum analysis were not specified in the abstract."},{"rthcId":"RPEP-03128","title":"The role of Neuropeptide Y in fear conditioning and extinction.","authors":"Tasan, R O; Verma, D; Wood, J; Lach, G; Hörmer, B; de Lima, T C M; Herzog, H; Sperk, G","year":2016,"journal":"Neuropeptides, 55, 111-26","doi":"10.1016/j.npep.2015.09.007","pmid":"26444585","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"NPY reduces fear expression primarily through Y1 receptors and promotes fear extinction via Y2 receptors in the amygdala. This dual action supports long-term fear suppression and highlights Y2 receptors as promising targets for anxiolytic therapies.","whyItMatters":"Identifying how NPY modulates fear and anxiety at the receptor level could lead to new, more effective treatments for anxiety disorders, which are often resistant to current therapies.","specificNumbers":"","methodology":"The study reviews preclinical research involving receptor-specific actions of NPY in brain regions related to fear, including knockout mouse models and electrophysiological analyses of neuronal activity.","limitations":"The study is largely based on preclinical data, and the exact roles of endogenous NPY and other receptor subtypes in humans remain unclear, requiring further research."},{"rthcId":"RPEP-03129","title":"Targeting the WASF3-CYFIP1 Complex Using Stapled Peptides Suppresses Cancer Cell Invasion.","authors":"Teng, Yong; Bahassan, Abdulaziz; Dong, Dayong; Hanold, Laura E; Ren, Xiaoou; Kennedy, Eileen J; Cowell, John K","year":2016,"journal":"Cancer research, 76(4), 965-73","doi":"10.1158/0008-5472.CAN-15-1680","pmid":"26676744","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Stapled peptides designed to disrupt the WASF3-CYFIP1 interaction significantly suppressed motility and invasion of highly invasive breast and prostate cancer cells in vitro. Genetic knockdown of CYFIP1 destabilized the WASF3 complex, leading to loss of WASF3 function and reduced invasion. The inhibition specifically affected WASF3 without impacting related proteins WASF1 and WASF2.","whyItMatters":"Targeting the WASF3 protein with stapled peptides offers a novel strategy to inhibit cancer cell invasion and metastasis, which are major challenges in cancer treatment. This approach could lead to therapies that prevent cancer spread by disrupting key protein interactions.","specificNumbers":"","methodology":"The study used genetic knockdown of CYFIP1 in cancer cells and designed stapled peptides (WAHM) based on crystallographic data to target the WASF3-CYFIP1 interface. Effects on cancer cell motility and invasion were assessed in vitro using breast and prostate cancer cell lines. Mechanistic studies examined interactions with Rac and downstream targets like MMP-9 and KISS1.","limitations":"The study was conducted in vitro, so effects in living organisms remain to be validated. The evidence strength and clinical applicability are not yet established."},{"rthcId":"RPEP-03130","title":"Aβ40 has a subtle effect on Aβ42 protofibril formation, but to a lesser degree than Aβ42 concentration, in Aβ42/Aβ40 mixtures.","authors":"Terrill-Usery, Shana E; Colvin, Benjamin A; Davenport, Richard E; Nichols, Michael R","year":2016,"journal":"Archives of biochemistry and biophysics, 597, 1-11","doi":"10.1016/j.abb.2016.03.017","pmid":"27013205","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03131","title":"Central ghrelin increases food foraging/hoarding that is blocked by GHSR antagonism and attenuates hypothalamic paraventricular nucleus neuronal activation.","authors":"Thomas, Michael A; Ryu, Vitaly; Bartness, Timothy J","year":2016,"journal":"American journal of physiology. Regulatory, integrative and comparative physiology, 310(3), R275-85","doi":"10.1152/ajpregu.00216.2015","pmid":"26561646","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Central administration of ghrelin into the third ventricle significantly increased food intake for 24 hours and food hoarding for 4 days in Siberian hamsters. Blocking the central ghrelin receptor with the antagonist JMV2959 prevented increases in food foraging, hoarding, and intake induced by peripheral ghrelin or food deprivation. Neuronal activation was reduced in the paraventricular hypothalamic nucleus following receptor blockade.","whyItMatters":"Understanding how central ghrelin signaling controls food-related behaviors helps clarify mechanisms of hunger and appetite regulation. This knowledge could inform treatments for eating disorders or obesity by targeting brain ghrelin pathways.","specificNumbers":"","methodology":"Siberian hamsters received injections of ghrelin directly into the third ventricle of the brain at three doses. Behavioral changes in food foraging, hoarding, and intake were measured. The ghrelin receptor antagonist JMV2959 was administered centrally to block these effects. Neuronal activation was assessed using c-Fos immunoreactivity in hypothalamic nuclei.","limitations":"The study was conducted only in Siberian hamsters, which may limit generalizability to other species. The exact neural circuits beyond the paraventricular nucleus involved were not fully explored."},{"rthcId":"RPEP-03132","title":"Stapling of unprotected helical peptides via photo-induced intramolecular thiol-yne hydrothiolation.","authors":"Tian, Yuan; Li, Jingxu; Zhao, Hui; Zeng, Xiangze; Wang, Dongyuan; Liu, Qisong; Niu, Xiaogang; Huang, Xuhui; Xu, Naihan; Li, Zigang","year":2016,"journal":"Chemical science, 7(5), 3325-3330","doi":"10.1039/c6sc00106h","pmid":"29997825","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Photo-induced intramolecular thiol-yne macrocyclization enables rapid synthesis of stapled peptides with enhanced helical stability, nanomolar binding affinity to estrogen receptor coactivators, improved serum stability, reduced membrane toxicity, and selective cytotoxicity against ER-positive cancer cells.","whyItMatters":"This new stapling method offers a faster, more versatile way to stabilize peptides, improving their potential as therapeutics targeting difficult intracellular proteins with better safety and efficacy profiles.","specificNumbers":"","methodology":"The study developed a photo-induced thiol-yne reaction to staple unprotected short peptides, creating conformationally constrained helices. The stapled peptides were characterized for binding affinity, serum stability, cellular distribution, and cytotoxicity in ER-positive MCF-7 cells.","limitations":"The study's evidence strength and sample size are not specified, and in vivo efficacy or long-term safety were not assessed, limiting conclusions about clinical potential."},{"rthcId":"RPEP-03133","title":"B-type natriuretic peptide and acute heart failure: Fluid homeostasis, biomarker and therapeutics.","authors":"Torres-Courchoud, I; Chen, H H","year":2016,"journal":"Revista clinica espanola, 216(7), 393-398","doi":"10.1016/j.rce.2016.01.009","pmid":"26961205","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BNP plays a critical role in fluid homeostasis and serves as both a biomarker and therapeutic agent in acute heart failure. Recombinant forms like Nesiritide are FDA-approved treatments, while others such as Ularitide are in advanced clinical trials.","whyItMatters":"Understanding BNP's dual role as a biomarker and treatment advances heart failure care and guides peptide-based therapeutic development.","specificNumbers":"","methodology":"This article is a review summarizing current knowledge and clinical developments regarding natriuretic peptides, particularly BNP, in acute heart failure management.","limitations":"The review does not present new experimental data and the evidence strength and study type are unspecified, limiting direct clinical conclusions."},{"rthcId":"RPEP-03134","title":"Endometriosis Is Associated With a Shift in MU Opioid and NMDA Receptor Expression in the Brain Periaqueductal Gray.","authors":"Torres-Reverón, Annelyn; Palermo, Karylane; Hernández-López, Anixa; Hernández, Siomara; Cruz, Myrella L; Thompson, Kenira J; Flores, Idhaliz; Appleyard, Caroline B","year":2016,"journal":"Reproductive sciences (Thousand Oaks, Calif.), 23(9), 1158-67","doi":"10.1177/1933719116630410","pmid":"27089914","tags":[],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"In a rat model of endometriosis, the condition caused significant changes in the brain's pain-processing center — the periaqueductal gray (PAG). After 60 days of endometriosis, mu opioid receptor (MOR) expression decreased by 20% and NMDA receptor (NR1) profiles decreased by 40% in the ventral PAG, despite no changes in endogenous opioid peptide levels (met-enkephalin, leu-enkephalin, and β-endorphin).\n\nThis means endometriosis doesn't reduce the brain's supply of natural painkillers — it reduces the receptors they need to work through. With fewer opioid receptors in the PAG, the brain's natural pain-dampening system becomes less effective, potentially explaining why endometriosis pain is so persistent and difficult to treat.","whyItMatters":"Endometriosis affects an estimated 10% of reproductive-age women and is notorious for causing severe, chronic pain that responds poorly to standard treatments. This study reveals that endometriosis physically rewires the brain's pain-modulation circuitry by downregulating key receptors. Understanding this central sensitization mechanism could explain why opioid painkillers often become less effective over time in endometriosis patients and could guide the development of more targeted pain therapies.","specificNumbers":"60-day endometriosis model · 20% decrease in MOR-expressing neurons · 40% decrease in NR1-expressing neurons · No change in met-enkephalin, leu-enkephalin, or β-endorphin levels · Ventral PAG specifically affected","methodology":"Researchers induced endometriosis in female Sprague-Dawley rats using the autotransplantation model (surgically relocating uterine tissue to create endometriotic lesions). After 60 days of disease progression, brain tissue was collected and the periaqueductal gray was analyzed using immunohistochemistry to quantify endogenous opioid peptides (met-enkephalin, leu-enkephalin, β-endorphin), mu opioid receptors, and NMDA NR1 receptor expression.","limitations":"The autotransplantation rat model doesn't perfectly replicate human endometriosis — the disease originates differently and the hormonal milieu differs. The study examined a single timepoint (60 days) and didn't assess whether these brain changes correlate with behavioral pain measures. The sample size isn't stated in the abstract. Whether these receptor changes are reversible with endometriosis treatment is unknown."},{"rthcId":"RPEP-03135","title":"Changes of growth hormone-releasing hormone and somatostatin neurons in the rat hypothalamus induced by genistein: a stereological study.","authors":"Trifunović, Svetlana; Manojlović-Stojanoski, Milica; Ristić, Nataša; Nestorović, Nataša; Medigović, Ivana; Živanović, Jasmina; Milošević, Verica","year":2016,"journal":"Nutritional neuroscience, 19(10), 467-474","doi":null,"pmid":"25087680","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Genistein administration at 30 mg/kg for three weeks increased the volume of the arcuate nucleus and the volume density of growth hormone-releasing hormone (GHRH) neurons by 26%, and somatostatin (SS) neurons by 1.5-fold in the hypothalamus of rats. This was accompanied by increased GHRH and SS staining intensity in the median eminence compared to controls.","whyItMatters":"Understanding how genistein affects hypothalamic neurons helps clarify its impact on growth hormone regulation and hormonal balance, which is important for evaluating its use in dietary and therapeutic supplements.","specificNumbers":"","methodology":"Adult rats were treated with genistein (30 mg/kg) daily for three weeks. Estradiol-dipropionate was used as a control treatment. Stereological analysis of hypothalamic sections quantified volumes and densities of GHRH and SS neurons, and image analysis measured peptide content in the median eminence.","limitations":"The study was conducted only in rats, limiting direct applicability to humans. The study type and evidence strength were not specified, and long-term effects were not assessed."},{"rthcId":"RPEP-03136","title":"Ba-Wei-Di-Huang-Wan through its active ingredient loganin counteracts substance P-enhanced NF-κB/ICAM-1 signaling in rats with bladder hyperactivity.","authors":"Tsai, Wen-Hsin; Wu, Chung-Hsin; Cheng, Chen-Hung; Chien, Chiang-Ting","year":2016,"journal":"Neurourology and urodynamics, 35(7), 771-9","doi":"10.1002/nau.22816","pmid":"26287995","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Ba-Wei-Di-Huang-Wan (BWDHW) and its active component loganin dose-dependently inhibited reactive oxygen species (H₂O₂ and HOCl) activity in vitro. In rats, oral pretreatment with BWDHW (250 mg/kg) or loganin (5 mg/kg) twice daily for two weeks significantly suppressed substance P-induced increases in voiding frequency, pelvic afferent nerve activity, NF-κB/ICAM-1 expression, leukocyte infiltration (neutrophils, monocytes/macrophages, and mast cells), and reactive oxygen species levels in the bladder.\n\nThe protective effects were mediated through inhibition of substance P/neurokinin-1 receptor signaling, which reduced downstream NF-κB activation, ICAM-1-mediated immune cell adhesion, and oxidative tissue injury.","whyItMatters":"Overactive bladder affects millions of people and current treatments often have significant side effects. This study identifies loganin as a specific active compound that targets the substance P inflammatory cascade — a well-known neuropeptide pathway involved in bladder dysfunction. By showing exactly how loganin interrupts this signaling chain, the research opens a potential path toward more targeted therapies with fewer side effects than current anticholinergic drugs.","specificNumbers":"","methodology":"Researchers used urethane-anesthetized female Wistar rats and induced bladder hyperactivity by injecting substance P directly into the blood supply. BWDHW and loganin were given orally twice daily for two weeks before testing. Bladder function was measured using cystometry (pressure recordings during filling and voiding), and nerve activity was recorded from the pelvic nerve. Inflammatory markers (NF-κB, ICAM-1) were assessed by Western blot and tissue staining, while oxidative stress was measured using ultrasensitive chemiluminescence. Immune cell infiltration was evaluated with specific stains for neutrophils, monocytes/macrophages, and mast cells.","limitations":"This study was conducted entirely in anesthetized rats, which limits direct translation to human bladder conditions experienced during normal activity. The substance P was administered externally rather than released naturally, which may not perfectly mimic the disease process. No human safety or efficacy data were generated, and the two-week treatment period is relatively short. The exact dosing needed for humans remains unknown."},{"rthcId":"RPEP-03137","title":"Neuropeptides CRH, SP, HK-1, and Inflammatory Cytokines IL-6 and TNF Are Increased in Serum of Patients with Fibromyalgia Syndrome, Implicating Mast Cells.","authors":"Tsilioni, Irene; Russell, Irwin J; Stewart, Julia M; Gleason, Rae M; Theoharides, Theoharis C","year":2016,"journal":"The Journal of pharmacology and experimental therapeutics, 356(3), 664-72","doi":"10.1124/jpet.115.230060","pmid":"26763911","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Three neuropeptides were significantly elevated in fibromyalgia serum: CRH (0.82 vs 0.49 ng/ml, P = 0.026), substance P (0.39 vs 0.12 ng/ml, P < 0.0001), and hemokinin-1 (7.98 vs 5.71 ng/ml, P = 0.002). SP and HK-1 levels were positively correlated (Pearson r = 0.45, P = 0.002).\n\nInflammatory cytokines IL-6 (2.97 vs 1.79 pg/ml, P = 0.029) and TNF (0.92 vs 0.69 pg/ml, P = 0.006) were also elevated. Conversely, IL-31 and IL-33 were significantly lower in fibromyalgia patients (P = 0.0001 and P = 0.044). Neurotensin levels showed no difference. The authors connect these findings to their prior work showing CRH and SP stimulate IL-6 and TNF release from mast cells.","whyItMatters":"Fibromyalgia affects 2-8% of the population and lacks reliable biomarkers or targeted treatments. This study identifies a specific neuropeptide-mast cell-cytokine pathway that could explain the widespread pain and inflammation in fibromyalgia. If confirmed, this pathway offers both diagnostic biomarker candidates and therapeutic targets — treatments blocking these neuropeptides or stabilizing mast cells could address the underlying biology rather than just managing symptoms.","specificNumbers":"","methodology":"Researchers measured serum concentrations of neuropeptides (CRH, substance P, hemokinin-1, neurotensin) and inflammatory cytokines (IL-6, TNF, IL-31, IL-33) in fibromyalgia patients and healthy controls using biochemical assays. Statistical comparisons between groups used appropriate tests, and Pearson correlation analysis assessed relationships between biomarkers.","limitations":"The specific sample size is not detailed in the abstract, limiting assessment of statistical power. This is a cross-sectional observational study, so causality cannot be established — elevated neuropeptides could be a cause, consequence, or correlate of fibromyalgia. Serum measurements may not reflect tissue-level neuropeptide concentrations at pain sites. The study did not control for medications that may affect neuropeptide or cytokine levels."},{"rthcId":"RPEP-03138","title":"Blast traumatic brain injury-induced cognitive deficits are attenuated by preinjury or postinjury treatment with the glucagon-like peptide-1 receptor agonist, exendin-4.","authors":"Tweedie, David; Rachmany, Lital; Rubovitch, Vardit; Li, Yazhou; Holloway, Harold W; Lehrmann, Elin; Zhang, Yongqing; Becker, Kevin G; Perez, Evelyn; Hoffer, Barry J; Pick, Chaim G; Greig, Nigel H","year":2016,"journal":"Alzheimer's & dementia : the journal of the Alzheimer's Association, 12(1), 34-48","doi":"10.1016/j.jalz.2015.07.489","pmid":"26327236","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Exendin-4 administered subcutaneously either 48 hours before or 2 hours after blast traumatic brain injury significantly reduced neurodegeneration at 72 hours, improved cognitive deficits observed between days 7 and 14, and attenuated blast-induced changes in dementia-related gene expression at day 14 postinjury in a mouse model.","whyItMatters":"This study identifies exendin-4 as a potential therapeutic agent for blast traumatic brain injury, a condition currently lacking approved treatments, and links blast injury effects to dementia-related pathways, highlighting new avenues for intervention.","specificNumbers":"","methodology":"Using a murine open field model of blast injury, exendin-4 was administered subcutaneously either as a pretreatment 48 hours before injury or as a postinjury treatment 2 hours after blast exposure. Neurodegeneration, cognitive behavior, and gene expression changes were assessed at multiple time points up to 14 days postinjury.","limitations":"The study was conducted in mice, so results may not fully translate to humans. The exact study type and strength of evidence were not specified, limiting assessment of reliability."},{"rthcId":"RPEP-03139","title":"The Cutaneous Microbiome and Aspects of Skin Antimicrobial Defense System Resist Acute Treatment with Topical Skin Cleansers.","authors":"Two, Aimee M; Nakatsuji, Teruaki; Kotol, Paul F; Arvanitidou, Evangelia; Du-Thumm, Laurence; Hata, Tissa R; Gallo, Richard L","year":2016,"journal":"The Journal of investigative dermatology, 136(10), 1950-1954","doi":"10.1016/j.jid.2016.06.612","pmid":"27377698","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Washing with common skin cleansers produced small but statistically significant decreases in LL-37 antimicrobial peptide levels on the skin surface shortly after washing. However, no significant changes were detected in bacterial community abundance or diversity. Group A Streptococcus did not survive better on washed skin compared to unwashed skin.\n\nIn contrast, soaps containing antimicrobial compounds (benzalkonium chloride or triclocarban) decreased the growth of Group A Streptococcus applied after rinsing, demonstrating that antimicrobial soap additives provide an additional protective effect beyond the mechanical cleaning action.","whyItMatters":"The skin microbiome and antimicrobial peptides are increasingly recognized as essential components of immune defense. As public health messaging emphasizes hand washing for infection prevention, it's important to confirm that this practice doesn't undermine the skin's natural protective systems. This study provides evidence that short-term washing is safe for the skin's innate defense mechanisms, supporting continued hand hygiene recommendations.","specificNumbers":"","methodology":"Human forearms were washed with several common skin cleansers. Researchers then measured the abundance of the antimicrobial peptide LL-37 on the skin surface, assessed bacterial DNA abundance and diversity through microbiome analysis, and tested whether Group A Streptococcus could survive better on washed versus unwashed skin. Soaps with and without antimicrobial additives were compared.","limitations":"The study only examined short-term (acute) effects of a single washing event. Long-term effects of chronic, repeated washing — as would occur with healthcare workers washing hands dozens of times daily — were not assessed. The study used a limited number of cleanser types, and results may not generalize to all skin care products. Individual variation in skin microbiome composition and LL-37 production was not extensively characterized."},{"rthcId":"RPEP-03140","title":"The opioid peptide beta-endorphin stimulates acrosome reaction in human spermatozoa.","authors":"Urizar-Arenaza, I; Estomba, H; Muñoa-Hoyos, I; Matorras, R; Esposito, A; Candenas, L; Pinto, F M; Valdivia, A; Irazusta, J; Subirán, N","year":2016,"journal":"Andrology, 4(1), 143-51","doi":"10.1111/andr.12133","pmid":"26663709","tags":["neuropeptides","reproductive-peptides"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Beta-endorphin, an opioid peptide known for pain relief and mood regulation, also triggers the acrosome reaction in human sperm — a critical step required for fertilization. The researchers found that beta-endorphin's precursor protein (pro-opiomelanocortin) is present in the middle section and tail of human sperm and in the seminiferous tubules of the testis. When beta-endorphin was applied to sperm in the lab, it increased the percentage of sperm undergoing the acrosome reaction in an inversely dose-dependent manner (lower doses had a stronger effect) through a calcium-independent protein kinase C pathway — a mechanism distinct from progesterone's effect on sperm.","whyItMatters":"The acrosome reaction is essential for a sperm to penetrate and fertilize an egg. Until now, progesterone was one of the only known regulators. The discovery that an opioid peptide also controls this process opens entirely new possibilities for both fertility treatments and non-hormonal contraception — potentially by targeting the opioid system in sperm rather than manipulating reproductive hormones.","specificNumbers":"Beta-endorphin precursor (POMC) found in sperm midpiece and flagellum · Inversely dose-dependent acrosome reaction · Calcium-independent PKC pathway · Present in seminiferous tubules","methodology":"Laboratory study using human sperm and testis tissue. Researchers used RT-PCR, western blot, and immunofluorescence to locate beta-endorphin's precursor protein in sperm. Flow cytometry measured acrosome reaction rates after beta-endorphin exposure. Intracellular calcium analysis determined whether the effect involved calcium signaling.","limitations":"This is an in vitro (lab dish) study — the findings have not been confirmed in living reproductive systems. Sample sizes are not specified in the abstract. The inversely dose-dependent response (lower doses work better) is unusual and needs further investigation. Whether the concentrations of beta-endorphin found naturally in follicular fluid are sufficient to trigger this effect in vivo remains unconfirmed."},{"rthcId":"RPEP-03141","title":"5-HT3 receptors promote colonic inflammation via activation of substance P/neurokinin-1 receptors in dextran sulphate sodium-induced murine colitis.","authors":"Utsumi, Daichi; Matsumoto, Kenjiro; Amagase, Kikuko; Horie, Syunji; Kato, Shinichi","year":2016,"journal":"British journal of pharmacology, 173(11), 1835-49","doi":"10.1111/bph.13482","pmid":"26990520","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Endogenous serotonin acts through 5-HT3 receptors to up-regulate inflammatory mediators and promote colonic inflammation in DSS-induced murine colitis. This effect is mediated via activation of substance P/neurokinin-1 (NK1) receptors on macrophages.","whyItMatters":"Understanding how serotonin and substance P contribute to colon inflammation could lead to new treatments for inflammatory bowel diseases by targeting these pathways.","specificNumbers":"","methodology":"The study used a mouse model of colitis induced by dextran sulphate sodium (DSS). Researchers administered 5-HT3 receptor antagonists (ramosetron, ondansetron) and an NK1 receptor antagonist (aprepitant) daily and assessed inflammation severity, inflammatory mediator expression, and receptor distribution using immunohistochemistry.","limitations":"The study was conducted in mice, so results may not fully translate to humans. The exact clinical relevance and long-term effects of blocking these receptors require further investigation."},{"rthcId":"RPEP-03142","title":"New role of biomarkers: mid-regional pro-adrenomedullin, the biomarker of organ failure.","authors":"Valenzuela-Sánchez, Francisco; Valenzuela-Méndez, Blanca; Rodríguez-Gutiérrez, Juan Francisco; Estella-García, Ángel; González-García, María Ángela","year":2016,"journal":"Annals of translational medicine, 4(17), 329","doi":null,"pmid":"27713887","tags":["adrenomedullin","biomarkers","sepsis"],"studyType":"Review","evidenceStrength":"Moderate","keyFinding":"Mid-regional pro-adrenomedullin (MR-proADM) — a stable surrogate marker for the peptide hormone adrenomedullin — is emerging as a superior biomarker for organ failure and mortality risk in sepsis patients. MR-proADM outperformed both procalcitonin (PCT) and C-reactive protein (CRP) for predicting unfavorable outcomes and death in ICU patients with sepsis.\n\nImportantly, MR-proADM levels are independent of the infecting organism — instead, they reflect the magnitude of organ failure itself, making it a severity marker rather than an infection marker. Serial MR-proADM measurements on days 2–5 of ICU admission help identify patients with poor prognosis. The review recommends adding MR-proADM to the standard biomarker panel for critically ill sepsis patients.","whyItMatters":"Sepsis kills more people than heart attacks and is notoriously difficult to diagnose and monitor. Current biomarkers like procalcitonin tell you about infection but not about organ failure — which is what actually kills sepsis patients. MR-proADM fills this gap by measuring the body's vasodilatory stress response, which directly reflects how badly organs are failing. Combining PCT (infection marker) with MR-proADM (organ failure marker) could give ICU doctors a much clearer picture of disease severity and guide treatment decisions.","specificNumbers":"MR-proADM > PCT > CRP for mortality prediction · organ failure severity independent of pathogen · serial levels days 2–5 most informative · ADM produced by bone, adrenal, kidney, lung, vessels, heart","methodology":"Narrative review synthesizing evidence from clinical studies on MR-proADM as a biomarker in sepsis and critical illness, comparing its prognostic performance to procalcitonin and CRP across emergency department and ICU settings.","limitations":"Narrative review without systematic search methodology. MR-proADM is not yet universally available in clinical laboratories. Optimal cutoff values for clinical decision-making are not standardized. Most supporting evidence comes from observational studies rather than interventional trials that show outcomes improve when MR-proADM guides treatment. The review focuses primarily on sepsis and may overstate generalizability to other critical illnesses."},{"rthcId":"RPEP-03143","title":"The Noncaloric Sweetener Rebaudioside A Stimulates Glucagon-Like Peptide 1 Release and Increases Enteroendocrine Cell Numbers in 2-Dimensional Mouse Organoids Derived from Different Locations of the Intestine.","authors":"van der Wielen, Nikkie; Ten Klooster, Jean Paul; Muckenschnabl, Susanne; Pieters, Raymond; Hendriks, Henk Fj; Witkamp, Renger F; Meijerink, Jocelijn","year":2016,"journal":"The Journal of nutrition, 146(12), 2429-2435","doi":null,"pmid":"27798332","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The stevia-derived sweetener rebaudioside A dramatically increased GLP-1 peptide release from mouse intestinal organoids: 1.7-fold in duodenum (p<0.01), 2.2-fold in jejunum (p<0.01), and 4.3-fold in ileum (p<0.001). It also increased PYY release 3-fold in the ileum (p<0.05). Long-term (18-hour) exposure increased expression of enteroendocrine cell markers: chromogranin A 3.5-fold, glucagon 3.5-fold, PYY 3.8-fold, and CCK 6.5-fold (all p<0.05 or better), suggesting rebaudioside A not only stimulates peptide secretion but also promotes enteroendocrine cell differentiation.","whyItMatters":"GLP-1 is the target of blockbuster diabetes and obesity drugs like semaglutide. This study suggests that a common zero-calorie sweetener can naturally stimulate GLP-1 and PYY release from gut cells. If confirmed in humans, this could mean stevia-based sweeteners have metabolic benefits beyond simply replacing sugar — they might actively promote the release of appetite-regulating and insulin-stimulating peptides.","specificNumbers":"GLP-1: 1.7-fold (duodenum), 2.2-fold (jejunum), 4.3-fold (ileum) · PYY: 3-fold (ileum) · chromogranin A: 3.5-fold · glucagon: 3.5-fold · PYY gene: 3.8-fold · CCK: 6.5-fold · 10 mmol/L rebaudioside A · 1h and 18h stimulation","methodology":"Researchers developed 2D organoids from mouse duodenal, jejunal, and ileal intestinal crypts. Organoids were characterized by gene expression and immunofluorescence, confirming the presence of enteroendocrine cells positive for GLP-1, PYY, and serotonin. Organoids were stimulated with 10 mmol/L rebaudioside A for 1 hour (secretion) or 18 hours (gene expression), and GLP-1, PYY, and CCK release and gene expression were measured.","limitations":"This is an ex vivo mouse organoid study — results may not translate to intact intestine or human physiology. The 10 mmol/L rebaudioside A concentration may be higher than physiologically achieved from dietary stevia consumption. The organoid model lacks the nervous system and blood supply that influence hormone secretion in vivo. Whether increased enteroendocrine marker expression translates to actual cell number increase was not definitively confirmed."},{"rthcId":"RPEP-03144","title":"Netnography of Female Use of the Synthetic Growth Hormone CJC-1295: Pulses and Potions.","authors":"Van Hout, Marie Claire; Hearne, Evelyn","year":2016,"journal":"Substance use & misuse, 51(1), 73-84","doi":"10.3109/10826084.2015.1082595","pmid":"26771670","tags":["growth-hormone-secretagogues"],"studyType":"qualitative","evidenceStrength":"preliminary","keyFinding":"Female users of CJC-1295 on online forums reported using the peptide primarily for weight loss, muscle enhancement, youthful skin, improved sleep, and injury healing. They demonstrated awareness of gender-specific differences in growth hormone pulses affecting dosing and cycling, and expressed concerns about potential long-term health consequences.\n\nForum users appeared experienced in combining multiple performance and image-enhancing drugs, with CJC-1295 being one product in a broader supplementation regimen.","whyItMatters":"Most peptide use research focuses on male bodybuilders. This study is one of the few to specifically examine female motivations and concerns around growth hormone peptides, revealing that women's reasons extend well beyond muscle building to include anti-aging and sleep quality — and that they recognize unique gender-related dosing challenges.","specificNumbers":"96 initial hits · 9 sites met criteria · 23 discussion threads analyzed · Focus: female CJC-1295 users","methodology":"Netnographic (online ethnographic) study. Researchers systematically searched the internet for forums discussing CJC-1295, applied exclusion criteria to focus on female users with active discussion, and analyzed 23 threads from 9 bodybuilding websites using the Empirical Phenomenological Psychological method.","limitations":"Forum data represents self-selected, anonymous users who may not be representative of all female CJC-1295 users. No way to verify actual use, dosing, or outcomes. The sample is drawn from bodybuilding forums, which skews toward fitness-focused individuals. No medical data or health outcomes were measured."},{"rthcId":"RPEP-03145","title":"The Role of Oxytocin in Parenting and as Augmentative Pharmacotherapy: Critical Issues and Bold Conjectures.","authors":"van IJzendoorn, M H; Bakermans-Kranenburg, M J","year":2016,"journal":"Journal of neuroendocrinology, 28(8)","doi":"10.1111/jne.12355","pmid":"26709101","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Intranasal oxytocin administration modulates brain activity by down-regulating amygdala responses to infant cues and enhances emotional salience, stress reduction, and empathic concern, particularly towards offspring and in-group members. However, effect sizes are small to modest, and current evidence is limited by small sample sizes and potential publication bias.","whyItMatters":"Understanding oxytocin's role could lead to new treatments for social and emotional disorders, but premature clinical use without sufficient evidence could be ineffective or unsafe.","specificNumbers":"","methodology":"The study is a review and meta-analysis of existing experimental research involving intranasal oxytocin administration in humans and animals, focusing on neural and behavioral effects related to parenting and social stimuli.","limitations":"Most studies reviewed have small sample sizes and are underpowered, leading to potential publication bias and limited replicability. The clinical use of oxytocin is premature due to insufficient safety and long-term effect data."},{"rthcId":"RPEP-03146","title":"Half-Life Extension of Biopharmaceuticals using Chemical Methods: Alternatives to PEGylation.","authors":"van Witteloostuijn, Søren B; Pedersen, Søren L; Jensen, Knud J","year":2016,"journal":"ChemMedChem, 11(22), 2474-2495","doi":"10.1002/cmdc.201600374","pmid":"27775236","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03147","title":"Balancing Accuracy and Cost of Confinement Simulations by Interpolation and Extrapolation of Confinement Energies.","authors":"Villemot, François; Capelli, Riccardo; Colombo, Giorgio; van der Vaart, Arjan","year":2016,"journal":"Journal of chemical theory and computation, 12(6), 2779-89","doi":"10.1021/acs.jctc.5b01183","pmid":"27120438","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The study presents an enhanced confinement simulation protocol that uses interpolation and extrapolation of confinement energies to optimize frequency spacing and reduce discretization errors. This approach decreased errors by 2- to 10-fold and sampling times by 8- to 67-fold for alanine n-peptides, and reduced sampling times by 10- to 100-fold for lactoferricin.","whyItMatters":"This advancement allows researchers to perform more accurate and faster peptide conformational energy calculations, which are critical for understanding peptide behavior and designing peptide-based therapeutics.","specificNumbers":"","methodology":"The method involves running simulations at multiple frequencies and leveraging phase space overlap to interpolate and extrapolate confinement energies. Relaxation time analysis was used to determine optimal simulation parameters such as time steps and friction coefficients. The protocol was applied to alanine n-peptides and lactoferricin to assess efficiency gains.","limitations":"The study does not specify the exact study type or provide evidence strength, limiting assessment of reproducibility. It focuses on specific peptides, so generalizability to other systems requires further validation."},{"rthcId":"RPEP-03148","title":"Ghrelin Receptor Ligands Reaching Clinical Trials: From Peptides to Peptidomimetics; from Agonists to Antagonists.","authors":"Vodnik, M; Štrukelj, B; Lunder, M","year":2016,"journal":"Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme, 48(1), 1-15","doi":"10.1055/s-0035-1564149","pmid":"26551992","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The ghrelin receptor (GHS-R1a) ligand field has evolved from peptide growth hormone secretagogues derived from Met-enkephalin to a diverse landscape of peptides, peptidomimetics, and small molecules. Several agonists reached clinical trials for growth hormone release, gastric emptying, and cachexia, but only GHRP-2 achieved approval (diagnostic use in Japan). The field has pivoted toward antagonists and inverse agonists targeting obesity and overweight, though none had reached market at the time of review.","whyItMatters":"The ghrelin system sits at the crossroads of hunger, metabolism, and growth hormone regulation. Despite the clinical failures of agonists, the ghrelin receptor remains a compelling drug target — particularly for obesity, where blocking hunger signaling could complement GLP-1-based approaches. Understanding past failures is essential for developing the next generation of anti-obesity peptide drugs.","specificNumbers":"","methodology":"Narrative review surveying the development history of ghrelin receptor ligands, including peptides, peptidomimetics, and small molecules. Focuses on compounds that reached clinical trials, covering agonists, antagonists, and inverse agonists with analysis of their therapeutic potential.","limitations":"This is a 2016 review and does not include developments from the past decade. The review summarizes existing literature without generating new data. Many of the compounds discussed never progressed beyond early clinical trials, and the reasons for clinical failure are not always clear from the available data."},{"rthcId":"RPEP-03149","title":"Identifying neuropeptide Y (NPY) as the main stress-related substrate of dipeptidyl peptidase 4 (DPP4) in blood circulation.","authors":"Wagner, Leona; Kaestner, Florian; Wolf, Raik; Stiller, Harald; Heiser, Ulrich; Manhart, Susanne; Hoffmann, Torsten; Rahfeld, Jens-Ulrich; Demuth, Hans-Ulrich; Rothermundt, Matthias; von Hörsten, Stephan","year":2016,"journal":"Neuropeptides, 57, 21-34","doi":"10.1016/j.npep.2016.02.007","pmid":"26988064","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Neuropeptide Y (NPY) is the primary substrate of DPP4 in blood circulation, with over 90% of DPP4-like activity attributed to soluble DPP4. Depressed patients showed reduced DPP4 activity and protein levels, which were restored following anti-depressive therapy. Additionally, GALP and Orexin B were identified as new DPP4 substrates.","whyItMatters":"Identifying NPY as the main DPP4 substrate links enzyme activity to stress and depression, suggesting that modulating DPP4 could influence neuropeptide regulation and mental health outcomes.","specificNumbers":"","methodology":"The study measured DPP4 enzyme activity and protein levels in sera from 32 depressed patients before and after treatment. It analyzed the degradation of various neuropeptides, including NPY, in serum and ex vivo human blood, and compared enzymatic truncation by soluble and membrane-bound DPP4 using rat brain perfusates and spiked sera.","limitations":"The study's sample size was relatively small and the exact study design was not specified, limiting generalizability. The evidence strength and study type were not clearly defined."},{"rthcId":"RPEP-03150","title":"Long-Acting C-Peptide and Neuropathy in Type 1 Diabetes: A 12-Month Clinical Trial.","authors":"Wahren, John; Foyt, Howard; Daniels, Mark; Arezzo, Joseph C","year":2016,"journal":"Diabetes care, 39(4), 596-602","doi":"10.2337/dc15-2068","pmid":"26884473","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03151","title":"Self-assembling peptide hydrogel for intervertebral disc tissue engineering.","authors":"Wan, Simon; Borland, Samantha; Richardson, Stephen M; Merry, Catherine L R; Saiani, Alberto; Gough, Julie E","year":2016,"journal":"Acta biomaterialia, 46, 29-40","doi":"10.1016/j.actbio.2016.09.033","pmid":"27677593","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The self-assembling peptide hydrogel (SAPH) demonstrated mechanical properties matching native human nucleus pulposus tissue and was deliverable via minimally invasive injection. In 3D culture, nucleus pulposus cells showed upregulation of NP-specific genes (KRT8, KRT18, FOXF1), confirming phenotype restoration after de-differentiation. Cell viability remained high throughout culture with a stable viable population. The SAPH stimulated time-dependent increases in aggrecan and type II collagen deposition — two critical extracellular matrix components of healthy disc tissue.","whyItMatters":"Lower back pain affects millions worldwide, and disc degeneration is a primary cause. Current treatments like spinal fusion or pain management don't regenerate damaged tissue. A peptide hydrogel that can be injected to restore disc structure and function could provide a minimally invasive, regenerative alternative — potentially addressing the root cause rather than just managing symptoms.","specificNumbers":"","methodology":"Researchers used oscillatory rheology to characterize the hydrogel's mechanical properties and injectability. Nucleus pulposus cells were cultured in 3D within the peptide hydrogel scaffold. Gene expression analysis measured NP-specific markers (KRT8, KRT18, FOXF1). Cell viability was tracked over time, and extracellular matrix production (aggrecan, type II collagen, glycosaminoglycans) was quantified to assess the scaffold's tissue engineering potential.","limitations":"This is an in vitro study without in vivo animal or human testing. Long-term stability of the hydrogel in the complex mechanical environment of the spine is unknown. The study used bovine nucleus pulposus cells, which may not perfectly replicate human cell behavior. No data on how the gel would perform under the dynamic loading conditions of a living spine."},{"rthcId":"RPEP-03152","title":"Chronic Peptide Therapy With B-Type Natriuretic Peptide in Patients With Pre-Clinical Diastolic Dysfunction (Stage B Heart Failure).","authors":"Wan, Siu-Hin; McKie, Paul M; Schirger, John A; Slusser, Joshua P; Hodge, David O; Redfield, Margaret M; Burnett, John C; Chen, Horng H","year":2016,"journal":"JACC. Heart failure, 4(7), 539-547","doi":"10.1016/j.jchf.2015.12.014","pmid":"26874387","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03153","title":"Biodistribution of the cyclotide MCoTI-II, a cyclic disulfide-rich peptide drug scaffold.","authors":"Wang, Conan K; Stalmans, Sofie; De Spiegeleer, Bart; Craik, David J","year":2016,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 22(5), 305-10","doi":"10.1002/psc.2862","pmid":"26929247","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"MCoTI-II, a cyclic disulfide-rich peptide, predominantly distributes to serum and kidneys in mice, indicating renal clearance, and does not penetrate the brain despite being a cell-penetrating peptide.","whyItMatters":"Understanding the distribution and clearance of stable cyclic peptides like MCoTI-II is crucial for developing them as drug scaffolds, especially for targeting specific organs or avoiding others like the brain.","specificNumbers":"","methodology":"The study compared the biodistribution of MCoTI-II in mice to other peptides and proteins by measuring their presence in various organs, focusing on serum, kidneys, and brain tissues.","limitations":"The study was conducted in mice, which may not fully represent human pharmacokinetics, and the exact doses and administration routes were not specified."},{"rthcId":"RPEP-03154","title":"Cyclic peptide oral bioavailability: Lessons from the past.","authors":"Wang, Conan K; Craik, David J","year":2016,"journal":"Biopolymers, 106(6), 901-909","doi":"10.1002/bip.22878","pmid":"27178381","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies key factors influencing the passive permeability and oral bioavailability of cyclic peptides, emphasizing structural features that enhance absorption. It highlights that cyclic peptides, unlike linear ones, can achieve drug-like oral bioavailability, as demonstrated by compounds such as cyclosporine A.","whyItMatters":"Understanding what makes cyclic peptides orally bioavailable can guide the design of new peptide drugs that are easier to administer and more effective. This knowledge is crucial for advancing peptide therapeutics beyond injections to convenient oral forms.","specificNumbers":"","methodology":"This study is a literature review analyzing past research on the oral bioavailability of peptides, focusing on passive permeability factors and comparing linear and cyclic peptide data.","limitations":"As a review, it summarizes existing studies but does not provide new experimental data. The evidence strength and study types of included research vary and are not specified."},{"rthcId":"RPEP-03155","title":"Inhibition of tau aggregation using a naturally-occurring cyclic peptide scaffold.","authors":"Wang, Conan K; Northfield, Susan E; Huang, Yen-Hua; Ramos, Mariana C; Craik, David J","year":2016,"journal":"European journal of medicinal chemistry, 109, 342-9","doi":"10.1016/j.ejmech.2016.01.006","pmid":"26807864","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The cyclic peptides SFTI-1 and kB1 inherently inhibit fibril formation of the tau-derived hexapeptide AcPHF6. Modifications to SFTI-1 enhanced its inhibitory potency, supporting the steric zipper model of tau fibril formation and highlighting these peptides as promising scaffolds for drug development.","whyItMatters":"Preventing tau protein aggregation is a key target in Alzheimer's research. This study shows that stable natural cyclic peptides can serve as effective inhibitors, offering new avenues for therapeutic development and molecular probes.","specificNumbers":"","methodology":"The study tested various naturally occurring cyclic peptides for their ability to inhibit fibril growth of the tau-derived hexapeptide AcPHF6. They applied an end-capping strategy and molecular grafting to modify SFTI-1 and assessed the effects on fibril formation.","limitations":"The study was conducted using a tau-derived hexapeptide fragment in vitro, which may not fully replicate the complexity of tau aggregation in living brains. The evidence strength and clinical relevance remain to be established."},{"rthcId":"RPEP-03156","title":"APD3: the antimicrobial peptide database as a tool for research and education.","authors":"Wang, Guangshun; Li, Xia; Wang, Zhe","year":2016,"journal":"Nucleic acids research, 44(D1), D1087-93","doi":"10.1093/nar/gkv1278","pmid":"26602694","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03157","title":"Angiotensin-Converting Enzyme 2 Metabolizes and Partially Inactivates Pyr-Apelin-13 and Apelin-17: Physiological Effects in the Cardiovascular System.","authors":"Wang, Wang; McKinnie, Shaun M K; Farhan, Maikel; Paul, Manish; McDonald, Tyler; McLean, Brent; Llorens-Cortes, Catherine; Hazra, Saugata; Murray, Allan G; Vederas, John C; Oudit, Gavin Y","year":2016,"journal":"Hypertension (Dallas, Tex. : 1979), 68(2), 365-77","doi":"10.1161/HYPERTENSIONAHA.115.06892","pmid":"27217402","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"ACE2 efficiently cleaves pyr-apelin 13 and apelin 17 peptides, reducing their vasodilatory and cardioprotective effects. ACE2 knockout or inhibition enhances apelin peptide activity, while ACE2-generated cleavage products lack these beneficial functions. Stable apelin analogues resistant to ACE2 degradation retain biological activity.","whyItMatters":"Understanding how ACE2 degrades apelin peptides helps explain their short lifespan and guides the design of more stable apelin-based drugs for cardiovascular diseases.","specificNumbers":"","methodology":"The study combined computer modeling, experiments in ACE2 knockout mice, pharmacological ACE2 inhibition, biochemical assays with recombinant ACE2, and functional tests on endothelial cells and myocardial ischemia-reperfusion models. Synthetic apelin analogues resistant to ACE2 cleavage were also designed and tested.","limitations":"The study does not specify clinical trial data or long-term effects of stable apelin analogues in humans, and the exact therapeutic potential remains to be confirmed."},{"rthcId":"RPEP-03158","title":"Acute versus chronic phase mechanisms in a rat model of CRPS.","authors":"Wei, Tzuping; Guo, Tian-Zhi; Li, Wen-Wu; Kingery, Wade S; Clark, John David","year":2016,"journal":"Journal of neuroinflammation, 13, 14","doi":"10.1186/s12974-015-0472-8","pmid":"26785976","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"At 4 weeks post-fracture (acute phase), 90% of rats showed pain behaviors (allodynia, unweighting), warmth, edema, and epidermal thickening. Substance P, NK1 receptor, TNFα, IL-1β, IL-6, and nerve growth factor (NGF) were all elevated in sciatic nerve and/or skin. By 16 weeks (chronic phase), only pain behaviors persisted — all peripheral inflammatory markers had returned to normal.\n\nCritically, spinal cord levels of NK1 receptor, TNFα, IL-1β, and NGF remained elevated at both 4 and 16 weeks. Peripheral administration of IL-1 receptor antagonist (anakinra) or anti-NGF blocked pain at 4 weeks but not 16 weeks. However, intrathecal (spinal) delivery of NK1 receptor antagonist, anakinra, or anti-NGF reduced pain at both timepoints, demonstrating that central mechanisms sustain chronic CRPS pain.","whyItMatters":"CRPS is notoriously difficult to treat, partly because the mechanisms maintaining chronic pain are poorly understood. This study demonstrates a clear shift from peripheral to central nervous system mechanisms as CRPS becomes chronic — explaining why treatments targeting peripheral inflammation often fail in long-standing cases. The finding that substance P/NK1 receptor signaling persists in the spinal cord provides a specific peptide-based target for developing therapies for chronic CRPS.","specificNumbers":"","methodology":"Researchers used a tibial fracture and cast immobilization model in male Sprague-Dawley rats to induce CRPS-like symptoms. They assessed nociceptive behaviors (von Frey testing for allodynia, unweighting), vascular changes (skin temperature and thickness), and molecular markers using immunoassays and Western blotting in skin, sciatic nerve, and spinal cord at 4 and 16 weeks. Pharmacological interventions included systemic (peripheral) and intrathecal (spinal) administration of NK1 receptor antagonist (LY303870), IL-1 receptor antagonist (anakinra), and anti-NGF antibody. Data were analyzed by one-way ANOVA with Newman-Keuls post hoc tests.","limitations":"The study was conducted in male Sprague-Dawley rats, and CRPS mechanisms may differ in females and in humans. The fracture/immobilization model reproduces some but not all features of human CRPS. Specific sample sizes per group were not stated in the abstract. The study did not explore the cellular mechanisms driving sustained spinal cord inflammation or whether longer treatment could reverse central sensitization. The 16-week timepoint, while chronic for rats, may not fully represent years-long human CRPS."},{"rthcId":"RPEP-03159","title":"Variation in the Oxytocin Receptor Gene Is Associated with Face Recognition and its Neural Correlates.","authors":"Westberg, Lars; Henningsson, Susanne; Zettergren, Anna; Svärd, Joakim; Hovey, Daniel; Lin, Tian; Ebner, Natalie C; Fischer, Håkan","year":2016,"journal":"Frontiers in behavioral neuroscience, 10, 178","doi":null,"pmid":"27713694","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The OXTR 3' polymorphism rs7632287 is associated with face recognition ability, where carriers of the GA genotype exhibit enhanced memory and increased amygdala activity during face encoding compared to GG genotype carriers.","whyItMatters":"Understanding how genetic variation in the oxytocin receptor influences social recognition and brain function can help clarify the biological mechanisms underlying social behavior and may inform treatments for social deficits.","specificNumbers":"","methodology":"The study analyzed nine polymorphisms in the oxytocin receptor gene and measured participants' face recognition ability alongside amygdala activity using functional magnetic resonance imaging (fMRI) during incidental face encoding.","limitations":"The study does not specify sample size or evidence strength, and the observational design limits causal conclusions; further research is needed to confirm findings."},{"rthcId":"RPEP-03160","title":"Discovery and optimization of peptide macrocycles.","authors":"White, Andrew M; Craik, David J","year":2016,"journal":"Expert opinion on drug discovery, 11(12), 1151-1163","doi":null,"pmid":"27718641","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Macrocyclic peptides demonstrate enhanced stability and potency compared to linear peptides, with the ability to target intracellular and extracellular proteins. Several macrocyclic peptides derived from natural sources or synthetically engineered are currently in clinical trials, highlighting their potential as next-generation therapeutics.","whyItMatters":"Macrocyclic peptides could overcome limitations of current drugs by combining potency, specificity, and cell penetration, offering new treatment options with potentially fewer side effects. Their production in plants could also reduce costs and improve global access.","specificNumbers":"","methodology":"This article reviews natural and synthetic macrocyclic peptides, discussing their structures, methods of cyclization, and potential as drug leads. It summarizes technologies for engineering cyclic peptides and evaluates their advantages over traditional small molecules and biologics.","limitations":"The study is a review and does not present new experimental data; the clinical efficacy and safety of many macrocyclic peptides remain to be fully established."},{"rthcId":"RPEP-03161","title":"Obesity in MENX Rats Is Accompanied by High Circulating Levels of Ghrelin and Improved Insulin Sensitivity.","authors":"Wiedemann, Tobias; Bielohuby, Maximilian; Müller, Timo D; Bidlingmaier, Martin; Pellegata, Natalia S","year":2016,"journal":"Diabetes, 65(2), 406-20","doi":"10.2337/db15-0374","pmid":"26512025","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"MENX rats with a p27 mutation developed pancreatic islet hyperplasia with elevated numbers of ghrelin-producing ε-cells, resulting in high plasma levels of both acylated and unacylated ghrelin. These rats showed increased food intake, enhanced body fat mass, and elevated triglycerides and cholesterol — effects confirmed by GHS-R1a antagonist treatment.\n\nParadoxically, despite obesity, MENX rats showed improved insulin sensitivity and decreased glucose-stimulated insulin secretion. At 7.5 months, hypothalamic GHS-R1a, NPY, and AgRP mRNA levels were decreased, suggesting prolonged high ghrelin may lead to reduced ghrelin signaling effectiveness (desensitization).","whyItMatters":"The finding that high ghrelin can drive obesity while simultaneously improving insulin sensitivity challenges the simplistic view of ghrelin as just a hunger hormone. Understanding how ghrelin separately regulates appetite and blood sugar could reveal new therapeutic targets — potentially allowing doctors to harness ghrelin's insulin-sensitizing effects without promoting weight gain.","specificNumbers":"","methodology":"MENX rats carrying a natural p27 mutation were characterized for metabolic phenotype including plasma ghrelin levels (acylated and unacylated), food intake, body fat composition, lipid profiles, and glucose metabolism. Hypothalamic gene expression (GHS-R1a, NPY, AgRP) was measured by mRNA analysis. A GHS-R1a antagonist was used to pharmacologically confirm ghrelin's role in increased food intake. Pancreatic tissue was analyzed for ghrelin-producing cell populations.","limitations":"This is an animal study using a specific genetic rat model (MENX), which may not fully represent human physiology. The p27 mutation causes multiple endocrine neoplasia, so effects may not be solely attributable to ghrelin elevation. The mechanisms underlying improved insulin sensitivity despite obesity were not fully elucidated. Sample sizes were not detailed in the abstract."},{"rthcId":"RPEP-03162","title":"Positioning SGLT2 Inhibitors/Incretin-Based Therapies in the Treatment Algorithm.","authors":"Wilding, John P H; Rajeev, Surya Panicker; DeFronzo, Ralph A","year":2016,"journal":"Diabetes care, 39 Suppl 2, S154-64","doi":"10.2337/dcS15-3005","pmid":"27440828","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"SGLT2 inhibitors and incretin-based therapies (DPP-4 inhibitors and GLP-1 receptor agonists) offer clinically important advantages over older diabetes drugs: weight loss, low hypoglycemia risk, blood pressure reduction, and — for empagliflozin specifically — reduced cardiovascular events in high-risk patients. These drugs may also correct core type 2 diabetes defects by improving β-cell function and insulin sensitivity. However, GLP-1 RAs carry nausea risk, SGLT2i are associated with genital infections, volume depletion, and rare diabetic ketoacidosis, and pancreatitis risk with incretins remains unclear.","whyItMatters":"Positioning newer diabetes drug classes in treatment algorithms is one of the most consequential clinical decisions in endocrinology. With older drugs like metformin and sulfonylureas as the baseline, the added benefits of SGLT2 inhibitors and incretin-based therapies — particularly cardiovascular protection and weight reduction — must be weighed against their higher cost and unique side effect profiles to determine where they fit best in stepped treatment approaches.","specificNumbers":"","methodology":"Narrative review article synthesizing clinical trial data, pharmacological rationale, and current treatment guidelines for SGLT2 inhibitors, DPP-4 inhibitors, and GLP-1 receptor agonists in type 2 diabetes. Discusses positioning of these drug classes relative to established therapies and anticipates how ongoing cardiovascular outcome trials may shift recommendations.","limitations":"Published in 2016, the review predates major cardiovascular outcome trials for GLP-1 RAs (LEADER, SUSTAIN-6, REWIND) and additional SGLT2i trials (DECLARE, DAPA-HF). At the time, empagliflozin was the only agent with cardiovascular outcome data. The review does not quantify the cost-effectiveness of newer therapies. The pancreatitis question with incretin therapies was unresolved at the time of publication."},{"rthcId":"RPEP-03163","title":"Renal Targeting: Peptide-Based Drug Delivery to Proximal Tubule Cells.","authors":"Wischnjow, Artjom; Sarko, Dikran; Janzer, Maria; Kaufman, Christina; Beijer, Barbro; Brings, Sebastian; Haberkorn, Uwe; Larbig, Gregor; Kübelbeck, Armin; Mier, Walter","year":2016,"journal":"Bioconjugate chemistry, 27(4), 1050-7","doi":"10.1021/acs.bioconjchem.6b00057","pmid":"26999755","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03164","title":"Teneurins, TCAP, and latrophilins: roles in the etiology of mood disorders.","authors":"Woelfle, Rebecca; D'Aquila, Andrea L; Lovejoy, David A","year":2016,"journal":"Translational neuroscience, 7(1), 17-23","doi":"10.1515/tnsci-2016-0004","pmid":"28123817","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review synthesizes evidence on the teneurin/TCAP-latrophilin system with several key findings:\n\n• TCAP peptides (1-4) are bioactive sequences embedded within teneurin proteins that are structurally similar to corticotropin-releasing factor (CRF), a peptide central to stress and mood disorders\n• Synthetic TCAP-1 induces long-term changes in neuronal structure in hippocampal cultures: increased neurite outgrowth, dendritic branching, and axon growth via an association with dystroglycans\n• In rodent behavioral models, TCAP-1 reduced anxiety responses in the elevated plus-maze, open-field test, and acoustic startle test\n• TCAP-1 inhibited CRF-mediated cocaine-seeking behavior\n• Teneurins interact with latrophilins (adhesion GPCRs) forming transsynaptic adhesion pairs, providing a structural and signaling basis for mood regulation","whyItMatters":"Current treatments for mood disorders primarily target serotonin, norepinephrine, and dopamine systems, but many patients don't respond adequately. The discovery of the teneurin/TCAP system introduces an entirely new peptide signaling axis that regulates both brain structure and anxiety-related behavior. Because TCAP resembles CRF — a well-validated stress target — but appears to have opposite effects (anxiolytic rather than anxiogenic), it could represent a new class of anti-anxiety peptide therapeutics.","specificNumbers":"","methodology":"Narrative review synthesizing findings from molecular biology (teneurin-latrophilin interaction characterization), in vitro neuronal culture experiments (embryonic and primary hippocampal cultures treated with synthetic TCAP-1), and behavioral pharmacology studies (rodent anxiety and addiction models).","limitations":"This is a narrative review of primarily preclinical data. All behavioral findings are from rodent models. No human data or clinical trials are described. The structural similarity between TCAP and CRF does not guarantee similar pharmacological utility. The mechanism by which TCAP-1 reduces anxiety while resembling an anxiogenic peptide family is not fully explained. Long-term safety of TCAP administration has not been evaluated."},{"rthcId":"RPEP-03165","title":"Gut hormone secretion, gastric emptying, and glycemic responses to erythritol and xylitol in lean and obese subjects.","authors":"Wölnerhanssen, Bettina K; Cajacob, Lucian; Keller, Nino; Doody, Alison; Rehfeld, Jens F; Drewe, Juergen; Peterli, Ralph; Beglinger, Christoph; Meyer-Gerspach, Anne Christin","year":2016,"journal":"American journal of physiology. Endocrinology and metabolism, 310(11), E1053-61","doi":"10.1152/ajpendo.00037.2016","pmid":"27117004","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Acute ingestion of erythritol and xylitol significantly increased plasma levels of gut hormones GLP-1 and CCK, which are involved in promoting satiation and slowing gastric emptying. Both sweeteners caused a marked delay in gastric emptying, while erythritol had no effect and xylitol only a slight effect on plasma glucose and insulin levels.","whyItMatters":"Understanding how sugar substitutes affect gut hormones and digestion can help develop better dietary strategies for obesity and diabetes management. These findings suggest erythritol and xylitol may support blood sugar control and satiety without raising insulin.","specificNumbers":"","methodology":"Ten lean and ten obese volunteers received glucose, xylitol, erythritol, or placebo via nasogastric tube. Plasma glucose, insulin, active GLP-1, CCK, and gastric emptying were measured using a 13C sodium acetate breath test. Subjective appetite was also assessed.","limitations":"The small sample size limits generalizability, and the acute administration via nasogastric tube may not reflect typical oral consumption. Long-term effects were not assessed."},{"rthcId":"RPEP-03166","title":"Growth Hormone-Releasing Hormone and Its Analogues: Significance for MSCs-Mediated Angiogenesis.","authors":"Xia, Xiangyang; Tao, Quanwei; Ma, Qunchao; Chen, Huiqiang; Wang, Jian'an; Yu, Hong","year":2016,"journal":"Stem cells international, 2016, 8737589","doi":null,"pmid":"27774107","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GHRH and its agonists enhance the angiogenic potential and tissue reparative properties of MSCs by activating the STAT3 signaling pathway. Treatment of MSCs with GHRH agonists prior to transplantation markedly improves their ability to promote blood vessel growth.","whyItMatters":"Enhancing MSC-mediated angiogenesis could improve regenerative medicine therapies for tissue repair and healing. Understanding how GHRH analogues boost MSC function opens new avenues for therapeutic development.","specificNumbers":"","methodology":"This is a review article summarizing existing research on the effects of GHRH and its analogues on MSCs, focusing on molecular pathways and angiogenesis. It includes analysis of experimental findings from various studies, including the authors' own laboratory work.","limitations":"As a review, this study does not present new experimental data and the evidence strength and study types vary across cited works. The precise clinical relevance and safety of GHRH analogues in humans require further investigation."},{"rthcId":"RPEP-03167","title":"Substance P enhances tissue factor release from granulocyte-macrophage colony-stimulating factor-dependent macrophages via the p22phox/β-arrestin 2/Rho A signaling pathway.","authors":"Yamaguchi, Rui; Yamamoto, Takatoshi; Sakamoto, Arisa; Ishimaru, Yasuji; Narahara, Shinji; Sugiuchi, Hiroyuki; Yamaguchi, Yasuo","year":2016,"journal":"Blood cells, molecules & diseases, 57, 85-90","doi":"10.1016/j.bcmd.2016.01.006","pmid":"26852662","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Substance P significantly enhances tissue factor release from GM-CSF-dependent macrophages via the p22phox/β-arrestin 2/Rho A signaling pathway. Inhibitors targeting neurokinin 1 receptor, reactive oxygen species, protein kinase C, ROCK, dynamin, and Akt partially or fully blocked this effect, and siRNA knockdown of p22phox, β-arrestin 2, or Rho A reduced tissue factor release.","whyItMatters":"Understanding how Substance P regulates tissue factor release from macrophages reveals mechanisms linking inflammation to blood clotting, which is important for diseases involving coagulation and immune responses.","specificNumbers":"","methodology":"The study used cultured GM-CSF-dependent macrophages stimulated with Substance P and measured tissue factor levels in cell lysates and culture supernatants using ELISA. Pharmacological inhibitors and siRNA were applied to dissect the signaling pathway involved. Additionally, visceral adipocytes were analyzed for Substance P production.","limitations":"The study does not specify the in vivo relevance or clinical implications, and the exact study type and evidence strength are not provided. The sample size and replication details are also not described."},{"rthcId":"RPEP-03168","title":"Absorption and Urinary Excretion of Peptides after Collagen Tripeptide Ingestion in Humans.","authors":"Yamamoto, Shoko; Deguchi, Kisaburo; Onuma, Masamichi; Numata, Noriaki; Sakai, Yasuo","year":2016,"journal":"Biological & pharmaceutical bulletin, 39(3), 428-34","doi":"10.1248/bpb.b15-00624","pmid":"26934933","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Ingestion of collagen tripeptide preparations containing Gly-X-Y sequences, such as Gly-Pro-Hyp, led to increased plasma and urinary levels of these peptides, demonstrating efficient absorption and stability of collagen-derived tripeptides in humans.","whyItMatters":"Understanding how collagen peptides are absorbed and processed helps improve the development of collagen-based supplements and therapies aimed at supporting skin, joint, and bone health.","specificNumbers":"","methodology":"Human subjects ingested different collagen preparations: a tripeptide-rich fraction (CTP-100), a 50% tripeptide collagen preparation (CTP-50), and a collagen peptide without tripeptides (CP). Postprandial plasma and urine samples were analyzed for specific collagen-derived peptides to assess absorption and excretion.","limitations":"The study did not specify the sample size or detailed participant characteristics, and the long-term effects of collagen peptide absorption were not assessed."},{"rthcId":"RPEP-03169","title":"Promising evidence and remaining issues regarding the clinical application of oxytocin in autism spectrum disorders.","authors":"Yamasue, Hidenori","year":2016,"journal":"Psychiatry and clinical neurosciences, 70(2), 89-99","doi":"10.1111/pcn.12364","pmid":"26394796","tags":["oxytocin","autism"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Single-dose oxytocin administration has consistently shown significant positive effects on experimental measures related to core autism spectrum disorder (ASD) symptoms in clinical trials. However, randomized clinical trials of continuous (multi-dose) oxytocin treatment have failed to show significant improvements in clinically meaningful endpoints — such as how individuals with ASD actually interact with other people in real-world situations.\n\nThe review identifies critical unresolved issues: optimal dose and duration remain unknown, the intranasal delivery system needs optimization, individual response variability is not well understood, and there is a lack of objective, reliable measurement tools for the core social symptoms of ASD.","whyItMatters":"There are currently no approved medications that treat the core social and communication symptoms of autism — existing drugs only address associated symptoms like irritability. Oxytocin, a naturally occurring neuropeptide involved in social bonding, remains one of the most promising candidates. This review provides a balanced, honest assessment: single-dose studies are encouraging, but the path to an actual treatment requires solving multiple practical challenges around dosing, delivery, and outcome measurement.","specificNumbers":"Single-dose trials: consistently positive effects on surrogate measures · Continuous administration trials: no significant effects on clinical endpoints · Key unresolved issues: dose optimization, treatment duration, delivery method, outcome measures, individual variability","methodology":"This is a narrative review of published clinical trials examining oxytocin's effects on ASD core symptoms. The author analyzed both single-dose studies (which used surrogate experimental measures) and randomized controlled trials of continuous oxytocin administration (which used clinically meaningful endpoints like social interaction quality).","limitations":"As a narrative review by a single author, the analysis may reflect interpretive choices not present in a systematic review or meta-analysis. The review is from 2016, so more recent trial data (including larger RCTs) published since then is not included. The field's reliance on surrogate endpoints in early trials makes it difficult to assess true clinical impact."},{"rthcId":"RPEP-03170","title":"Substance P Inhibits Hyperosmotic Stress-Induced Apoptosis in Corneal Epithelial Cells through the Mechanism of Akt Activation and Reactive Oxygen Species Scavenging via the Neurokinin-1 Receptor.","authors":"Yang, Lingling; Sui, Wenjie; Li, Yunqiu; Qi, Xia; Wang, Yao; Zhou, Qingjun; Gao, Hua","year":2016,"journal":"PloS one, 11(2), e0149865","doi":"10.1371/journal.pone.0149865","pmid":"26901348","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Substance P protected mouse corneal epithelial cells from hyperosmotic stress-induced apoptosis through multiple mechanisms working through the NK-1 receptor:\n- Restored phosphorylated Akt levels (cell survival signaling)\n- Recovered mitochondrial membrane potential\n- Normalized intracellular calcium levels\n- Scavenged reactive oxygen species (ROS)\n- Restored glutathione levels (antioxidant defense)\n\nBlocking the NK-1 receptor with an antagonist impaired both Akt activation and ROS scavenging, confirming that substance P's protective effects are mediated specifically through this receptor. Akt inhibition or glutathione depletion partially suppressed the anti-apoptotic capacity, demonstrating both pathways contribute to protection.","whyItMatters":"Dry eye disease affects hundreds of millions of people worldwide and current treatments primarily address symptoms rather than the underlying cell damage. This study reveals that substance P — already present in the cornea's nerve supply — can protect corneal cells from the specific type of damage that drives dry eye progression. This supports developing substance P-based eye drops as a disease-modifying treatment rather than just symptom relief.","specificNumbers":"","methodology":"Mouse corneal epithelial cells were cultured and exposed to hyperosmotic stress (high glucose). Cells were treated with substance P in the presence or absence of specific inhibitors: an Akt inhibitor, a glutathione-depleting agent, and an NK-1 receptor antagonist. Endpoints included apoptosis rates, Akt phosphorylation, mitochondrial membrane potential, calcium levels, ROS levels, and glutathione concentrations.","limitations":"This is an in vitro study using mouse corneal epithelial cell lines, which may not fully replicate human corneal biology or the complex tear film environment. Hyperosmotic stress was induced with high glucose, which may have metabolic effects beyond osmolarity. The study did not test whether substance P can be effectively delivered as eye drops. In vivo validation in animal dry eye models was not performed. The dose-response relationship for substance P protection was not characterized."},{"rthcId":"RPEP-03171","title":"The effect of oxytocin nasal spray on social interaction deficits observed in young children with autism: a randomized clinical crossover trial.","authors":"Yatawara, C J; Einfeld, S L; Hickie, I B; Davenport, T A; Guastella, A J","year":2016,"journal":"Molecular psychiatry, 21(9), 1225-31","doi":"10.1038/mp.2015.162","pmid":"26503762","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Oxytocin nasal spray administered at 24 IU per day for five weeks significantly improved caregiver-rated social responsiveness in young children with autism compared to placebo. The treatment was well tolerated with mild side effects such as thirst, increased urination, and constipation.","whyItMatters":"This study provides early clinical evidence that oxytocin nasal spray may be a promising intervention to improve social deficits in young children with autism, a population with limited treatment options.","specificNumbers":"","methodology":"A double-blind, randomized, placebo-controlled, crossover clinical trial was conducted with 31 young children diagnosed with autism. Participants received oxytocin nasal spray and placebo each for five weeks, separated by a four-week washout period. Social responsiveness was assessed by caregiver ratings.","limitations":"The study sample size was relatively small, and the evidence strength and long-term effects remain unclear. Further larger and longer-term studies are needed to confirm efficacy and safety."},{"rthcId":"RPEP-03172","title":"Compared to Sleeve Gastrectomy, Duodenal-Jejunal Bypass with Sleeve Gastrectomy Gives Better Glycemic Control in T2DM Patients, with a Lower β-Cell Response and Similar Appetite Sensations: Mixed-Meal Study.","authors":"Zachariah, Pulimuttil James; Chen, Chih-Yen; Lee, Wei-Jei; Chen, Shu-Chu; Ser, Kong-Han; Chen, Jung-Chien; Lee, Yi-Chih","year":2016,"journal":"Obesity surgery, 26(12), 2862-2872","doi":null,"pmid":"27138599","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"At one year post-surgery, the duodenal-jejunal bypass with sleeve gastrectomy (DJB-SG) group achieved 62% complete diabetes remission (HbA1c < 6.0%) compared to 32% in the sleeve gastrectomy (SG) group (P < 0.05), despite similar total body weight loss (25.7% vs. 22%). The DJB-SG group showed significantly lower postprandial blood glucose levels and lower C-peptide levels during mixed-meal tolerance testing, indicating improved glycemic control with reduced beta-cell secretory demand.\n\nNo significant differences were found in appetite sensations between groups, suggesting the metabolic benefit of duodenal-jejunal exclusion operates through gut hormone signaling pathways rather than changes in food intake behavior.","whyItMatters":"This study provides mechanistic evidence that bypassing the duodenum and upper jejunum improves diabetes outcomes through changes in peptide hormone signaling — not just weight loss or reduced eating. The lower C-peptide levels in the DJB-SG group suggest beta-cell preservation, which could mean longer-lasting diabetes remission. This has implications for understanding how gut-derived peptide hormones like GLP-1 and GIP regulate blood sugar.","specificNumbers":"","methodology":"This retrospective comparative study included 46 type 2 diabetes patients — 21 who underwent DJB-SG and 25 who had SG alone. All patients completed mixed-meal tolerance tests (MMTT) before surgery and at one year, with blood glucose, C-peptide, and insulin measured at multiple time points. Appetite was assessed using visual analogue scales rating six different appetite sensations during the meal test.","limitations":"This was a retrospective study with a small sample size of 46 patients, without randomization or blinding. The one-year follow-up may not reflect long-term durability of diabetes remission. The study did not directly measure gut peptide hormones like GLP-1 or GIP, which would have provided stronger mechanistic evidence. Selection bias may exist between the two surgical groups, as patient characteristics differed at baseline."},{"rthcId":"RPEP-03173","title":"Design of Decorated Self-Assembling Peptide Hydrogels as Architecture for Mesenchymal Stem Cells.","authors":"Zamuner, Annj; Cavo, Marta; Scaglione, Silvia; Messina, Grazia Maria Lucia; Russo, Teresa; Gloria, Antonio; Marletta, Giovanni; Dettin, Monica","year":2016,"journal":"Materials (Basel, Switzerland), 9(9)","doi":"10.3390/ma9090727","pmid":"28773852","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Hydrogels functionalized with peptide conjugates containing adhesive sequences or IGF-1 significantly increased mesenchymal stem cell adhesion and proliferation. These 3D scaffolds supported cell spreading and elongation without compromising the hydrogel's viscoelastic properties.","whyItMatters":"This research advances the development of biomimetic 3D scaffolds that better replicate the natural environment of stem cells, potentially improving cell culture techniques and therapeutic delivery systems.","specificNumbers":"","methodology":"The study involved chemically linking bioactive molecules to a self-assembling ionic complementary peptide (EAK) to create decorated hydrogels. Mesenchymal stem cell adhesion assays and small amplitude oscillatory shear tests were conducted to evaluate cell behavior and hydrogel mechanical properties.","limitations":"The study does not specify the quantitative extent of cell proliferation increase or long-term stability of the hydrogels, and the exact study type and evidence strength are not reported."},{"rthcId":"RPEP-03174","title":"Neuroprotective Effects of Peptides during Ischemic Preconditioning.","authors":"Zarubina, I V; Shabanov, P D","year":2016,"journal":"Bulletin of experimental biology and medicine, 160(4), 448-51","doi":"10.1007/s10517-016-3193-9","pmid":"26902350","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03175","title":"Oxytocin is implicated in social memory deficits induced by early sensory deprivation in mice.","authors":"Zhang, Jin-Bao; Chen, Ling; Lv, Zhu-Man; Niu, Xue-Yuan; Shao, Can-Can; Zhang, Chan; Pruski, Michal; Huang, Ying; Qi, Cong-Cong; Song, Ning-Ning; Lang, Bing; Ding, Yu-Qiang","year":2016,"journal":"Molecular brain, 9(1), 98","doi":null,"pmid":"27964753","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Mice with early-life unilateral infraorbital nerve transection exhibited deficits in social and spatial memory without affecting other behaviors. The social memory deficit correlated with decreased hypothalamic oxytocin levels and was partially reversed by intranasal oxytocin administration.","whyItMatters":"Understanding how early sensory experiences influence oxytocin signaling and social memory can help develop interventions for neurodevelopmental disorders involving social deficits.","specificNumbers":"","methodology":"Researchers performed unilateral transection of the infraorbital nerve in mice at postnatal day 3 to induce early sensory deprivation. Adult mice were then assessed for various behaviors including locomotion, anxiety, memory, and social interaction. Oxytocin levels were measured in the hypothalamus, and intranasal oxytocin was administered to test for behavioral rescue.","limitations":"The study does not specify the sample size or use a controlled experimental design, and the evidence strength is unclear. Effects were only partially reversed by oxytocin, indicating other mechanisms may be involved."},{"rthcId":"RPEP-03176","title":"Antimicrobial Peptide LL37 and MAVS Signaling Drive Interferon-β Production by Epidermal Keratinocytes during Skin Injury.","authors":"Zhang, Ling-Juan; Sen, George L; Ward, Nicole L; Johnston, Andrew; Chun, Kimberly; Chen, Yifang; Adase, Christopher; Sanford, James A; Gao, Nina; Chensee, Melanie; Sato, Emi; Fritz, Yi; Baliwag, Jaymie; Williams, Michael R; Hata, Tissa; Gallo, Richard L","year":2016,"journal":"Immunity, 45(1), 119-30","doi":"10.1016/j.immuni.2016.06.021","pmid":"27438769","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Epidermal keratinocytes produce high levels of interferon-β during skin injury and psoriasis through MAVS signaling activated by the antimicrobial peptide LL37 and double-stranded RNA from necrotic cells. This MAVS-dependent pathway triggers the TBK1-AKT-IRF3 cascade, promoting interferon-β production and dendritic cell maturation.","whyItMatters":"Understanding how keratinocytes produce interferon-β via LL37 and MAVS reveals key mechanisms driving skin inflammation in diseases like psoriasis and wound healing. This knowledge could guide development of targeted therapies to control harmful skin inflammation.","specificNumbers":"","methodology":"The study used human psoriatic and wounded skin samples and mouse models to investigate interferon-β production by keratinocytes. Molecular analyses identified the role of LL37, MAVS, and downstream signaling components in activating interferon-β expression and immune responses.","limitations":"The study does not specify the exact study type or provide detailed quantitative data on sample sizes, limiting assessment of evidence strength. Further research is needed to confirm findings in larger cohorts and clinical settings."},{"rthcId":"RPEP-03177","title":"Dipeptidyl Peptidase IV-Inhibitory Peptides Derived from Silver Carp (Hypophthalmichthys molitrix Val.) Proteins.","authors":"Zhang, Ying; Chen, Ran; Chen, Xiling; Zeng, Zhu; Ma, Huiqin; Chen, Shangwu","year":2016,"journal":"Journal of agricultural and food chemistry, 64(4), 831-9","doi":"10.1021/acs.jafc.5b05429","pmid":"26758401","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Silver carp protein hydrolysates generated by various proteases demonstrated efficient DPP-IV inhibitory activity, with Neutrase hydrolysates showing the strongest inhibition (IC50 = 1.12 mg/mL). Two newly identified peptides, LPIIDI and APGPAGP, exhibited potent DPP-IV inhibition with IC50 values of 105.44 μM and 229.14 μM, respectively, acting via mixed competitive/non-competitive inhibition.","whyItMatters":"Identifying natural peptides that inhibit DPP-IV offers potential for developing functional foods or supplements to help manage diabetes through diet, expanding options beyond synthetic drugs.","specificNumbers":"","methodology":"The study used enzymatic hydrolysis of silver carp proteins with six different proteases, followed by in silico analysis to predict peptide fragments. Peptides were separated and identified using liquid chromatography-tandem mass spectrometry (LC-MS/MS), and selected peptides were chemically synthesized to test their DPP-IV inhibitory activity.","limitations":"The study did not include in vivo testing to confirm the peptides' effectiveness in living organisms, and the exact bioavailability and stability of these peptides in the human digestive system remain unknown."},{"rthcId":"RPEP-03178","title":"Elevation of Fasting Ghrelin in Healthy Human Subjects Consuming a High-Salt Diet: A Novel Mechanism of Obesity?","authors":"Zhang, Yong; Li, Fenxia; Liu, Fu-Qiang; Chu, Chao; Wang, Yang; Wang, Dan; Guo, Tong-Shuai; Wang, Jun-Kui; Guan, Gong-Chang; Ren, Ke-Yu; Mu, Jian-Jun","year":2016,"journal":"Nutrients, 8(6)","doi":"10.3390/nu8060323","pmid":"27240398","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Fasting plasma ghrelin levels were significantly higher during a high-salt diet (320.7 ± 30.6 pg/mL) compared to a low-salt diet (172.9 ± 8.9 pg/mL, p<0.01) in 38 healthy, non-obese adults. This represents an approximate 85% increase in the hunger hormone. A positive correlation between 24-hour urinary sodium excretion and fasting ghrelin levels was also demonstrated, suggesting a dose-response relationship between salt intake and ghrelin production.","whyItMatters":"Epidemiological studies have linked high salt intake to obesity, but the biological mechanism was unclear. This study proposes that salt drives up ghrelin — the peptide hormone that stimulates hunger and fat storage — offering a concrete physiological pathway that could explain why salty diets contribute to weight gain beyond just calorie intake.","specificNumbers":"n=38 · ghrelin on high salt: 320.7 pg/mL · ghrelin on low salt: 172.9 pg/mL · ~85% increase · p<0.01 · low salt: 3 g/day · high salt: 18 g/day · 7-day interventions","methodology":"Crossover dietary intervention in 38 healthy, non-obese, normotensive adults aged 25–50 from rural Northern China. Participants were sequentially placed on a normal diet for 3 days, a low-salt diet (3 g/day NaCl) for 7 days, then a high-salt diet (18 g/day NaCl) for 7 days. Fasting plasma ghrelin was measured by ELISA and 24-hour urinary sodium excretion was monitored to verify dietary compliance.","limitations":"Small sample size of 38 participants. The sequential (non-randomized) design means order effects cannot be ruled out. The study only measured ghrelin over short 7-day periods and did not track actual changes in appetite, food intake, or body weight. All participants were from a single rural Chinese community, limiting generalizability."},{"rthcId":"RPEP-03179","title":"Prenatal nicotinic exposure upregulates pulmonary C-fiber NK1R expression to prolong pulmonary C-fiber-mediated apneic response.","authors":"Zhao, Lei; Zhuang, Jianguo; Zang, Na; Lin, Yong; Lee, Lu-Yuan; Xu, Fadi","year":2016,"journal":"Toxicology and applied pharmacology, 290, 107-15","doi":"10.1016/j.taap.2015.10.023","pmid":"26524655","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Prenatal nicotine exposure (PNE) significantly upregulated both mRNA and protein levels of NK1R (Substance P receptor) and TRPV1 in the nodose/jugular ganglia, and NK1R mRNA specifically in pulmonary C-neurons. This upregulation prolonged apneic responses to capsaicin. The NK1R antagonist SR140333 significantly shortened the PNE-induced prolonged apnea, confirming NK1R's functional role.\n\nThe mechanism was traced to nicotinic acetylcholine receptors: both mecamylamine (general nAChR antagonist) and methyllycaconitine (selective α7nAChR antagonist) eliminated the PNE-evoked receptor upregulation, identifying α7nAChR as the key mediator of nicotine's effect on peptide receptor expression.","whyItMatters":"Sudden infant death syndrome (SIDS) and neonatal breathing disorders are more common in babies exposed to nicotine during pregnancy. This study identifies a specific neuropeptide receptor mechanism — NK1R upregulation — that explains how prenatal nicotine sensitizes lung sensory nerves, causing exaggerated and dangerous breathing pauses. This could guide development of interventions for at-risk newborns.","specificNumbers":"","methodology":"Pregnant rats received nicotine via mini-pump during gestation. Rat pups were studied for: Substance P and adenosine levels in bronchoalveolar lavage fluid, NK1R/ADA1R/TRPV1 expression (mRNA and protein) in nodose/jugular ganglia and retrogradely-labeled pulmonary C-neurons, and apneic responses to intravenous capsaicin with and without NK1R antagonist pretreatment. Additional groups received nAChR antagonists during the prenatal exposure period to identify the upstream mechanism.","limitations":"The study was conducted in Sprague-Dawley rats, and the nicotine delivery (mini-pump) does not replicate the intermittent exposure pattern of human smoking. The study focused on acute apneic responses and did not assess long-term respiratory outcomes. Whether NK1R antagonists could safely be used in human neonates is unknown. The relationship between these findings and SIDS risk is inferred, not directly demonstrated."},{"rthcId":"RPEP-03180","title":"Expressions of Antimicrobial Peptides LL-37, Human Beta Defensin-2 and -3 in the Lesions of Cutaneous Tuberculosis and Tuberculids.","authors":"Zhao, Zheng; Mu, Zhang-Lei; Liu, Xi-Wan; Liu, Xiao-Jing; Jia, Jun; Cai, Lin; Zhang, Jian-Zhong","year":2016,"journal":"Chinese medical journal, 129(6), 696-701","doi":"10.4103/0366-6999.178011","pmid":"26960373","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The expression of LL-37 and HBD-3 mRNA and protein in lesions of cutaneous tuberculosis and tuberculids was similar to normal skin, whereas HBD-2 mRNA showed an increasing trend but its protein expression decreased in cutaneous tuberculosis lesions, indicating possible post-transcriptional regulation differences between these conditions.","whyItMatters":"Understanding how antimicrobial peptides behave in skin infections like tuberculosis can help clarify the immune response and potentially guide new treatments targeting these peptides.","specificNumbers":"","methodology":"The study analyzed fresh and paraffin-embedded skin biopsy samples from patients with cutaneous tuberculosis, tuberculids, and healthy controls. Quantitative real-time PCR measured mRNA levels, while immunohistochemistry and Western blotting assessed protein expression of LL-37, HBD-2, and HBD-3.","limitations":"The study's small sample size limits the generalizability of the findings, and the mechanisms regulating peptide expression remain unclear."},{"rthcId":"RPEP-03181","title":"Upregulated expression of substance P in basophils of the patients with chronic spontaneous urticaria: induction of histamine release and basophil accumulation by substance P.","authors":"Zheng, Wenjiao; Wang, Junling; Zhu, Wei; Xu, Chiyan; He, Shaoheng","year":2016,"journal":"Cell biology and toxicology, 32(3), 217-28","doi":"10.1007/s10565-016-9330-4","pmid":"27147256","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Patients with CSU exhibit elevated plasma levels of substance P and increased percentages of SP+ and NK1R+ basophils. Substance P induces up to 41.2% net histamine release from basophils, comparable to anti-IgE and fMLP stimulation, and promotes basophil accumulation in vivo, indicating its role as a potent proinflammatory mediator in CSU pathogenesis.","whyItMatters":"Understanding how substance P drives basophil activation and histamine release helps identify new therapeutic targets for CSU, a condition with limited treatment options. Targeting substance P or its receptor NK1R could reduce inflammation and symptoms.","specificNumbers":"","methodology":"The study used flow cytometry to analyze basophils from CSU patients and healthy controls, basophil challenge assays to measure histamine release upon substance P stimulation, and a mouse sensitization model to observe basophil accumulation after substance P administration.","limitations":"The study type and evidence strength are not specified, and the sample size details are unclear, limiting assessment of generalizability. The exact clinical efficacy of SP or NK1R inhibitors in CSU remains to be tested."},{"rthcId":"RPEP-03182","title":"Thapsigargin-induced activation of Ca(2+)-CaMKII-ERK in brainstem contributes to substance P release and induction of emesis in the least shrew.","authors":"Zhong, Weixia; Chebolu, Seetha; Darmani, Nissar A","year":2016,"journal":"Neuropharmacology, 103, 195-210","doi":"10.1016/j.neuropharm.2015.11.023","pmid":"26631534","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Thapsigargin induces vomiting in the least shrew through activation of the Ca(2+)-CaMKII-ERK1/2 signaling pathway in the brainstem, which elevates substance P levels and activates neurokinin-1 receptors. Pharmacological blockade of calcium channels, CaMKII, ERK1/2, and neurokinin-1 receptors attenuates or abolishes the emetic response.","whyItMatters":"Understanding how thapsigargin causes vomiting helps clarify the role of calcium signaling and substance P in emesis, which is important for developing better antiemetic treatments, especially since thapsigargin derivatives are being tested as cancer drugs.","specificNumbers":"","methodology":"The study used intraperitoneal injections of thapsigargin in least shrews to induce vomiting and measured brainstem biochemical changes including phosphorylation of CaMKII and ERK1/2 and substance P levels. Various receptor antagonists and channel blockers were administered to assess their effects on vomiting and associated signaling pathways.","limitations":"The study was conducted in least shrews, which may not fully replicate human emetic responses, and the exact clinical relevance of thapsigargin-induced vomiting in humans remains to be determined."},{"rthcId":"RPEP-03183","title":"Cross-talk between 5-hydroxytryptamine and substance P in the melanogensis and apoptosis of B16F10 melanoma cells.","authors":"Zhou, Jia; Geng, Kun-kun; Ping, Feng-feng; Gao, Yue-ying; Liu, Lei; Feng, Bai-nian","year":2016,"journal":"European journal of pharmacology, 775, 106-12","doi":"10.1016/j.ejphar.2016.02.026","pmid":"26872989","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Substance P inhibits the expression of the 5-HT2A receptor, thereby neutralizing serotonin-induced melanogenesis in B16F10 melanoma cells. Concurrently, substance P upregulates NK1 receptor expression and directly induces apoptosis in these cells, effects that can be mitigated by serotonin or 5-HT2A receptor agonists.","whyItMatters":"Understanding the interaction between substance P and serotonin receptors in melanocytes offers insights into how stress-related molecules influence skin pigmentation and melanoma cell survival, which is valuable for peptide-based therapeutic development.","specificNumbers":"","methodology":"The study used in vitro experiments on B16F10 melanoma cells to analyze receptor expression changes and apoptosis after treatment with substance P, serotonin, and receptor antagonists/agonists. Molecular assays measured receptor levels and cell viability.","limitations":"The study was conducted in vitro using a melanoma cell line, which may not fully replicate in vivo skin physiology or the complexity of human pigmentation and melanoma progression."},{"rthcId":"RPEP-03184","title":"Beneficial Effect of Intermedin 1-53 in Septic Shock Rats: Contributions of Rho Kinase and BKCA Pathway-Mediated Improvement in Cardiac Function.","authors":"Zhu, Yu; Wu, Huiling; Wu, Yue; Zhang, Jie; Peng, Xiaoyong; Zang, Jiatao; Xiang, Xinming; Liu, Liangming; Li, Tao","year":2016,"journal":"Shock (Augusta, Ga.), 46(5), 557-565","doi":null,"pmid":"27355401","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"IMD1-53 (0.5 μg/kg) administered to septic shock rats demonstrated:\n\n• Significantly improved animal survival with both early (immediately after CLP) and late (12 hours after CLP) administration\n• Increased cardiac contractility and function\n• Improved tissue perfusion and oxygen delivery\n• Early administration produced better results than late administration\n\nMechanistically, IMD1-53 acted through two pathways:\n1. Rho kinase/TnI pathway: IMD1-53 increased Rho kinase expression in cardiac muscle and inhibited troponin I (TnI) phosphorylation\n2. BKCa channel pathway: IMD1-53 inhibited BKCa channel currents and reduced intracellular calcium concentration in cardiomyocytes\n\nBoth pathways were confirmed by pharmacological blockade — a Rho kinase inhibitor (Y-27632) or BKCa opener (NS1619) abolished IMD1-53's protective effects.","whyItMatters":"Septic shock kills millions worldwide, and cardiac dysfunction during sepsis is a major driver of mortality. Current treatments focus on antibiotics and fluid resuscitation but have limited ability to directly support the failing heart. A peptide-based therapy that can rescue cardiac function in sepsis — even when given late — could represent a genuine advance in critical care medicine.","specificNumbers":"","methodology":"Septic shock was induced in Sprague-Dawley rats using cecal ligation and puncture (CLP), a standard model. IMD1-53 was given at 0.5 μg/kg either immediately or 12 hours post-CLP. Outcomes included survival, cardiac papillary muscle contractility, cardiomyocyte function, tissue perfusion, and oxygen delivery. Pathway involvement was confirmed using pharmacological inhibitors. BKCa channel currents and intracellular calcium were measured electrophysiologically.","limitations":"Conducted entirely in rats — septic shock pathophysiology and treatment responses can differ significantly in humans. The CLP model, while standard, may not replicate the complexity of clinical sepsis. A single dose (0.5 μg/kg) was tested; dose-response relationships are not established. No comparison to standard sepsis therapies. Long-term outcomes beyond survival were not assessed. The peptide's pharmacokinetics and stability in vivo were not characterized."},{"rthcId":"RPEP-03185","title":"Stable gastric pentadecapeptide BPC 157 and bupivacaine.","authors":"Zivanovic-Posilovic, Gordana; Balenovic, Diana; Barisic, Ivan; Strinic, Dean; Stambolija, Vasilije; Udovicic, Mario; Uzun, Sandra; Drmic, Domagoj; Vlainic, Josipa; Bencic, Martina Lovric; Sindic, Aleksandra; Seiwerth, Sven; Sikiric, Predrag","year":2016,"journal":"European journal of pharmacology, 793, 56-65","doi":"10.1016/j.ejphar.2016.10.035","pmid":"27815173","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BPC 157 prevented and counteracted bupivacaine cardiotoxicity in rats across an extremely wide dose range (10 pg/kg to 50 µg/kg). Given 30 minutes before or 1 minute after bupivacaine (100 mg/kg), it largely counteracted bradycardia, AV-block, ventricular arrhythmias, T-wave elevation, and asystole. Even when given 6 minutes after bupivacaine (after prolonged QRS had developed), it markedly postponed fatal outcomes. In vitro, BPC 157 (1 µM) inhibited bupivacaine-induced cell membrane depolarization in HEK293 cells.","whyItMatters":"Accidental bupivacaine overdose during local anesthesia can cause fatal heart arrhythmias, and current rescue options are limited. BPC 157’s ability to counteract cardiotoxicity across a million-fold dose range and even after arrhythmias have begun suggests a potential emergency antidote. The lack of known BPC 157 toxicity adds to its appeal as a rescue agent.","specificNumbers":"Bupivacaine 100 mg/kg · BPC 157: 50 µg/kg to 10 pg/kg effective · pre-treatment (30 min) and post-treatment (1 min, 6 min) · QRS prolongation ≥20 ms threshold · 1 µM inhibited depolarization in vitro","methodology":"Wistar rats received toxic-dose bupivacaine (100 mg/kg IP). BPC 157 was administered at four dose levels either 30 min before, 1 min after, or 6 min after bupivacaine. ECG monitoring assessed cardiac rhythm disturbances (bradycardia, AV-block, ventricular arrhythmias, QRS prolongation, T-wave elevation, asystole). In vitro, membrane voltage (Vm) was measured in HEK293 cells exposed to bupivacaine (1 mM) ± BPC 157 (1 µM).","limitations":"Rat model only — human cardiac physiology differs, and bupivacaine toxicity patterns may not be identical. The mechanism of cardioprotection is not fully elucidated. No human safety or efficacy data for this application. The extreme dose range (pg to µg) is unusual and the mechanism driving activity across such a range is unclear. All research comes from a single research group (Sikiric lab)."},{"rthcId":"RPEP-03186","title":"A Prospective, Randomized, Masked, Placebo-Controlled Clinical Study of Capromorelin in Dogs with Reduced Appetite.","authors":"Zollers, B; Wofford, J A; Heinen, E; Huebner, M; Rhodes, L","year":2016,"journal":"Journal of veterinary internal medicine, 30(6), 1851-1857","doi":"10.1111/jvim.14607","pmid":"27859746","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Capromorelin at 3 mg/kg orally once daily significantly increased appetite in 68.6% of treated dogs compared to 44.6% in placebo, with a corresponding mean body weight increase of 1.8% versus 0.1% in placebo over 4 days (P = .008).","whyItMatters":"Stimulating appetite in dogs with poor eating can improve their health and recovery. Capromorelin is the first ghrelin receptor agonist shown effective for this purpose, offering a new therapeutic option.","specificNumbers":"","methodology":"This was a prospective, randomized, masked, placebo-controlled clinical trial involving 244 client-owned dogs with reduced appetite for at least 2 days. Dogs received either capromorelin oral solution (3 mg/kg) or placebo daily. Owners assessed appetite at baseline and after 3 ± 1 days. Safety was monitored via physical exams, clinical pathology, and adverse event reporting.","limitations":"The study duration was short (4 days), so long-term effects and safety remain unknown. Owner-reported appetite is subjective and may introduce bias."},{"rthcId":"RPEP-03187","title":"Braverman 2017 Gh Replacement Cancer Meta","authors":"","year":2017,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03188","title":"Haycock 2017 Ltl Mortality Meta","authors":"","year":2017,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03189","title":"Haycock 2017 Mr Telomere Cancer","authors":"","year":2017,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03190","title":"James 2017 Orexin Opioid Addiction Review","authors":"","year":2017,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03191","title":"Sack 2017 Oxytocin Prevention Ptsd Emergency","authors":"","year":2017,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03192","title":"A second dose of kisspeptin-54 improves oocyte maturation in women at high risk of ovarian hyperstimulation syndrome: a Phase 2 randomized controlled trial.","authors":"Abbara, Ali; Clarke, Sophie; Islam, Rumana; Prague, Julia K; Comninos, Alexander N; Narayanaswamy, Shakunthala; Papadopoulou, Deborah; Roberts, Rachel; Izzi-Engbeaya, Chioma; Ratnasabapathy, Risheka; Nesbitt, Alexander; Vimalesvaran, Sunitha; Salim, Rehan; Lavery, Stuart A; Bloom, Stephen R; Huson, Les; Trew, Geoffrey H; Dhillo, Waljit S","year":2017,"journal":"Human reproduction (Oxford, England), 32(9), 1915-1924","doi":"10.1093/humrep/dex253","pmid":"28854728","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03193","title":"Predictable Peptide Conjugation Ratios by Activation of Proteins with Succinimidyl Iodoacetate (SIA).","authors":"Abbas, Ioana M; Schwaar, Timm; Bienwald, Frank; Weller, Michael G","year":2017,"journal":"Methods and protocols, 1(1)","doi":"10.3390/mps1010002","pmid":"31164550","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The study demonstrated that activation of proteins with succinimidyl iodoacetate (SIA) enables the preparation of peptide-protein conjugates with predefined and reproducible conjugation ratios, avoiding the drawbacks of maleimide-based linkers such as unwanted byproducts and immunogenicity.","whyItMatters":"This method improves the reliability and predictability of peptide-protein conjugation, which is crucial for developing consistent bioconjugates in peptide research and therapeutic applications.","specificNumbers":"","methodology":"The researchers examined the use of the heterobifunctional linker SIA for protein activation and developed two protocols to conjugate cysteine-containing peptides to proteins. They compared this approach to traditional methods involving maleimide linkers and reductive or thiolation treatments.","limitations":"The study does not specify the exact sample sizes or provide quantitative data on conjugation efficiency. The evidence strength and study type are not clearly defined, limiting assessment of robustness."},{"rthcId":"RPEP-03194","title":"A meta-analysis comparing clinical effects of short- or long-acting GLP-1 receptor agonists versus insulin treatment from head-to-head studies in type 2 diabetic patients.","authors":"Abd El Aziz, Mirna S; Kahle, Melanie; Meier, Juris J; Nauck, Michael A","year":2017,"journal":"Diabetes, obesity & metabolism, 19(2), 216-227","doi":"10.1111/dom.12804","pmid":"27717195","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03195","title":"Proteasome inhibitor MG132 modulates inflammatory pain by central mechanisms in adjuvant arthritis.","authors":"Ahmed, Aisha Siddiqah; Ahmed, Mahmood; Li, Jian; Gu, Harvest F; Bakalkin, Georgy; Stark, André; Harris, Helena Erlandsson","year":2017,"journal":"International journal of rheumatic diseases, 20(1), 25-32","doi":"10.1111/1756-185X.12353","pmid":"24702728","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"MG132 treatment in arthritic rats significantly reduced substance P gene expression and the number of substance P-positive cells in the dorsal root ganglia and spinal cord. Additionally, MG132 downregulated NF-κB DNA-binding activity in the spinal cord, indicating a mechanism involving inhibition of NF-κB activation.","whyItMatters":"Understanding how MG132 reduces pain by targeting substance P and NF-κB pathways could lead to new treatments for inflammatory pain in rheumatoid arthritis and other conditions.","specificNumbers":"","methodology":"Arthritis was induced in rats using heat-killed Mycobacterium butyricum. MG132 was administered daily, and molecular changes were assessed by quantitative PCR, immunohistochemistry for substance P, and electromobility shift assay for NF-κB activity in dorsal root ganglia and spinal cord tissues.","limitations":"The study was conducted in a rat model, so results may not fully translate to humans. The exact dosing regimen and long-term effects were not detailed."},{"rthcId":"RPEP-03196","title":"Orai1-Mediated Antimicrobial Secretion from Pancreatic Acini Shapes the Gut Microbiome and Regulates Gut Innate Immunity.","authors":"Ahuja, Malini; Schwartz, Daniella M; Tandon, Mayank; Son, Aran; Zeng, Mei; Swaim, William; Eckhaus, Michael; Hoffman, Victoria; Cui, Yiyuan; Xiao, Bo; Worley, Paul F; Muallem, Shmuel","year":2017,"journal":"Cell metabolism, 25(3), 635-646","doi":"10.1016/j.cmet.2017.02.007","pmid":"28273482","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Deletion of the Orai1 calcium channel in pancreatic acinar cells led to a 60%-70% mortality rate in mice within three weeks due to intestinal bacterial overgrowth and dysbiosis despite activation of innate immunity. Reduced pancreatic cathelicidin-related antimicrobial peptide (CRAMP) levels were observed, and supplementation with synthetic CRAMP prevented intestinal disease and improved survival.","whyItMatters":"Understanding how pancreatic antimicrobial peptides regulate gut bacteria and immunity could lead to new treatments for intestinal diseases and improve health by targeting these peptides or their pathways.","specificNumbers":"","methodology":"The study used genetically modified adult mice lacking the Orai1 calcium channel specifically in pancreatic acinar cells. Researchers monitored survival, gut microbiome composition, immune responses, and intestinal health. Treatments included digestive enzyme supplementation, purified liquid diet, broad-spectrum antibiotics, and synthetic CRAMP peptide supplementation.","limitations":"The study was conducted in mice, so results may not fully translate to humans; the exact mechanisms linking Orai1 deletion to antimicrobial peptide secretion require further clarification."},{"rthcId":"RPEP-03197","title":"l-phenylalanine modulates gut hormone release and glucose tolerance, and suppresses food intake through the calcium-sensing receptor in rodents.","authors":"Alamshah, A; Spreckley, E; Norton, M; Kinsey-Jones, J S; Amin, A; Ramgulam, A; Cao, Y; Johnson, R; Saleh, K; Akalestou, E; Malik, Z; Gonzalez-Abuin, N; Jomard, A; Amarsi, R; Moolla, A; Sargent, P R; Gray, G W; Bloom, S R; Murphy, K G","year":2017,"journal":"International journal of obesity (2005), 41(11), 1693-1701","doi":"10.1038/ijo.2017.164","pmid":"28792489","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Oral and ileal administration of l-phenylalanine in rodents acutely and chronically reduced food intake and body weight, stimulated the release of gut hormones GLP-1 and PYY, reduced plasma ghrelin, and improved glucose tolerance. These effects were mediated through activation of the calcium-sensing receptor (CaSR), as pharmacological blockade of CaSR attenuated these responses.","whyItMatters":"Understanding how l-phenylalanine and the calcium-sensing receptor regulate appetite and glucose metabolism could lead to new treatments for obesity and diabetes by targeting gut hormone pathways.","specificNumbers":"","methodology":"The study administered l-phenylalanine orally and directly into the ileum of rats and mice, measuring food intake, body weight, gut hormone levels, and glucose tolerance. In vitro experiments used STC-1 and primary L cells to assess GLP-1 release and the role of CaSR via pharmacological blockade.","limitations":"The study was conducted in rodents, so the findings may not fully translate to humans. The exact physiological role of CaSR in human protein sensing and appetite regulation remains to be clarified."},{"rthcId":"RPEP-03198","title":"Metabolic and immune effects of immunotherapy with proinsulin peptide in human new-onset type 1 diabetes.","authors":"Alhadj Ali, Mohammad; Liu, Yuk-Fun; Arif, Sefina; Tatovic, Danijela; Shariff, Hina; Gibson, Vivienne B; Yusuf, Norkhairin; Baptista, Roman; Eichmann, Martin; Petrov, Nedyalko; Heck, Susanne; Yang, Jennie H M; Tree, Timothy I M; Pujol-Autonell, Irma; Yeo, Lorraine; Baumard, Lucas; Stenson, Rachel; Howell, Alex; Clark, Alison; Boult, Zoe; Powrie, Jake; Adams, Laura; Wong, Florence S; Luzio, Stephen; Dunseath, Gareth; Green, Kate; O'Keefe, Alison; Bayly, Graham; Thorogood, Natasha; Andrews, Robert; Leech, Nicola; Joseph, Frank; Nair, Sunil; Seal, Susan; Cheung, HoYee; Beam, Craig; Hills, Robert; Peakman, Mark; Dayan, Colin M","year":2017,"journal":"Science translational medicine, 9(402)","doi":"10.1126/scitranslmed.aaf7779","pmid":"28794283","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03199","title":"Emerging Roles for MAS-Related G Protein-Coupled Receptor-X2 in Host Defense Peptide, Opioid, and Neuropeptide-Mediated Inflammatory Reactions.","authors":"Ali, Hydar","year":2017,"journal":"Advances in immunology, 136, 123-162","doi":"10.1016/bs.ai.2017.06.002","pmid":"28950944","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"MRGPRX2 is selectively expressed on MCTC-type mast cells and is activated by host defense peptides, neuropeptides, opioids, and various cationic drugs, contributing to both host defense and chronic inflammatory diseases such as severe asthma, rosacea, and atopic dermatitis.","whyItMatters":"Understanding MRGPRX2's dual role in immune defense and inflammation could lead to targeted therapies that enhance protection against infections while reducing harmful inflammatory responses and adverse drug reactions.","specificNumbers":"","methodology":"This study is a comprehensive review of existing research on MRGPRX receptors, focusing on MRGPRX2 expression, signaling mechanisms, and roles in mast cell function, host defense, inflammatory diseases, and drug-induced reactions.","limitations":"As a review, the study synthesizes existing data without new experimental evidence; the exact mechanisms and clinical implications of MRGPRX2 signaling require further investigation."},{"rthcId":"RPEP-03200","title":"Neuropeptide Y in the brain of Euphlyctis cyanophlyctis tadpoles responds to hypoxic stress.","authors":"Ali, Ishfaq; Bhargava, Shobha","year":2017,"journal":"General and comparative endocrinology, 251, 38-45","doi":"10.1016/j.ygcen.2016.09.011","pmid":"27663883","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Exposure to hypoxia (<2 mg/ml oxygen) significantly increased neuropeptide Y immunoreactivity in multiple brain regions of Euphlyctis cyanophlyctis tadpoles, including areas involved in stress and respiratory regulation.","whyItMatters":"Understanding how neuropeptide Y responds to hypoxia in lower vertebrates expands knowledge of stress regulation mechanisms and may inform research on brain adaptation to oxygen deprivation.","specificNumbers":"","methodology":"The study used immunohistochemistry to examine neuropeptide Y distribution in the brains of tadpoles exposed to normal and low oxygen levels. Brain regions were analyzed for changes in neuropeptide Y immunoreactivity.","limitations":"The study does not specify the exact functional outcomes of increased neuropeptide Y or the behavioral effects on tadpoles, and the study type and evidence strength are not clearly defined."},{"rthcId":"RPEP-03201","title":"High-concentration topical capsaicin may abolish the clinical manifestations of allergic contact dermatitis by effects on induction and elicitation.","authors":"Andersen, Hjalte H; Elberling, Jesper; Arendt-Nielsen, Lars","year":2017,"journal":"Medical hypotheses, 99, 53-56","doi":"10.1016/j.mehy.2016.12.012","pmid":"28110699","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Topical application of 8% capsaicin patches can induce temporary defunctionalization of peptidergic nerve fibers, which play a key role in both the induction and elicitation phases of allergic contact dermatitis, potentially abolishing clinical symptoms.","whyItMatters":"This research highlights a novel neuro-immune mechanism in allergic contact dermatitis and suggests a new topical treatment strategy that targets nerve fibers rather than the immune system directly, which could improve management of this common skin condition.","specificNumbers":"","methodology":"The study reviews recent human experimental protocols using prolonged application of high-concentration topical capsaicin patches to achieve temporary defunctionalization of peptidergic nerve fibers. It combines these protocols with experimental allergic contact dermatitis models to explore the role of nerve fibers in disease development.","limitations":"The study is a hypothesis and review rather than a clinical trial, so direct evidence of efficacy in patients is limited. The exact duration and safety of prolonged high-concentration capsaicin use require further investigation."},{"rthcId":"RPEP-03202","title":"Cellular Mucins: Targets for Immunotherapy.","authors":"Apostolopoulos, Vasso; McKenzie, Ian F C","year":2017,"journal":"Critical reviews in immunology, 37(2-6), 421-437","doi":"10.1615/CritRevImmunol.v37.i2-6.110","pmid":"29773028","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"MUC1 mucins are overexpressed and abnormally glycosylated in adenocarcinomas, creating novel peptide and carbohydrate epitopes that are immunogenic. The peptide APDTR within the VNTR region elicits strong antibody responses and cytotoxic T cell precursors in breast cancer patients, supporting mucins as promising immunotherapy targets.","whyItMatters":"Targeting mucins could improve cancer immunotherapy by focusing on tumor-specific markers absent in normal tissues, potentially leading to more effective and less toxic treatments.","specificNumbers":"","methodology":"This review synthesizes findings from molecular cloning, immunological assays in mice and humans, and early clinical trials evaluating mucin-based vaccines. It highlights immunogenic epitopes identified through antibody and T cell studies and discusses ongoing vaccine development programs.","limitations":"The evidence strength and study type are not clearly defined, and clinical trial results on vaccine efficacy remain preliminary. Further large-scale studies are needed to confirm therapeutic benefits."},{"rthcId":"RPEP-03203","title":"Anticancer activities of bovine and human lactoferricin-derived peptides.","authors":"Arias, Mauricio; Hilchie, Ashley L; Haney, Evan F; Bolscher, Jan G M; Hyndman, M Eric; Hancock, Robert E W; Vogel, Hans J","year":2017,"journal":"Biochemistry and cell biology = Biochimie et biologie cellulaire, 95(1), 91-98","doi":"10.1139/bcb-2016-0175","pmid":"28165293","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The cyclized LFcinB-CLICK peptide exhibited enhanced anticancer activity compared to other lactoferricin-derived peptides. Short peptides hLF11 and bLF10 were not cytotoxic alone, but when hLF11 was linked to the antimicrobial core sequence of LFcinB, toxicity to Jurkat leukemia cells increased significantly. These findings highlight the potential of combining cell-penetrating and antimicrobial peptide sequences to improve anticancer potency.","whyItMatters":"This work identifies new peptide candidates that selectively kill cancer cells, which could lead to novel anticancer therapies. Understanding how to enhance peptide activity by combining sequences may improve the design of effective peptide-based drugs.","specificNumbers":"","methodology":"The study tested various peptides derived from bovine and human lactoferrin on leukemia and breast cancer cell lines as well as normal blood cells in vitro. Peptides included linear and cyclized forms, and chimeric peptides combining different sequences were evaluated for cytotoxic effects.","limitations":"The study was conducted in vitro, so results may not fully translate to living organisms. The exact mechanisms of increased cytotoxicity and potential side effects were not explored in detail."},{"rthcId":"RPEP-03204","title":"Rationale for treatment options for mealtime glucose control in patients with type 2 diabetes.","authors":"Aronoff, Stephen L","year":2017,"journal":"Postgraduate medicine, 129(2), 231-241","doi":"10.1080/00325481.2017.1285191","pmid":"28118069","tags":["glp-1-receptor-agonists"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Different classes of diabetes medications have similar effects on HbA1c but vary significantly in how well they control after-meal blood sugar spikes. Short-acting GLP-1 receptor agonists like exenatide twice daily and lixisenatide have a stronger effect on postprandial glucose than longer-acting GLP-1 drugs, primarily because they slow stomach emptying more. Injectable options including prandial insulin analogs, GLP-1 receptor agonists, and the amylin analog pramlintide all effectively target post-meal blood sugar. DPP-4 inhibitors and SGLT2 inhibitors also reduce postprandial spikes.","whyItMatters":"After-meal blood sugar spikes are a major contributor to diabetes complications that standard measures like HbA1c and fasting glucose can miss. This review highlights that not all diabetes drugs are equal when it comes to controlling these spikes, giving doctors a framework for matching treatments to patients who struggle with post-meal glucose surges.","specificNumbers":"","methodology":"Narrative literature review based on a PubMed search of clinical studies examining treatments for mealtime glucose control in type 2 diabetes. Compared the effects of multiple drug classes on postprandial hyperglycemia, glucose fluctuations, and overall glycemic control.","limitations":"This is a narrative review, not a systematic review or meta-analysis, so it may not capture all relevant studies. No new experimental data was generated. The quality and comparability of the included studies may vary. Published in 2017, so newer therapies and data (including tirzepatide and oral semaglutide) are not covered."},{"rthcId":"RPEP-03205","title":"Empirical and bioinformatic characterization of buffalo (Bubalus bubalis) colostrum whey peptides & their angiotensin I-converting enzyme inhibition.","authors":"Ashok, N R; Aparna, H S","year":2017,"journal":"Food chemistry, 228, 582-594","doi":"10.1016/j.foodchem.2017.02.032","pmid":"28317767","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Seventy-four peptides were identified from buffalo colostrum whey, many with functions including ACE inhibition. A synthesized octapeptide (IQKVAGTW) demonstrated ACE inhibitory activity with an IC50 of 300±2 µM in vitro.","whyItMatters":"Identifying natural ACE inhibitory peptides from buffalo colostrum offers potential for developing nutraceuticals or therapies to manage hypertension, expanding options beyond synthetic drugs.","specificNumbers":"","methodology":"Buffalo colostrum and milk whey proteins were digested using simulated in vitro digestion and analyzed by nano-LC-MS/MS. Functional protein networks and gene annotations were performed, followed by synthesis and in vitro testing of a selected ACE inhibitory peptide.","limitations":"The ACE inhibitory activity was demonstrated only in vitro; in vivo efficacy and safety remain to be established. The study did not specify clinical or animal testing."},{"rthcId":"RPEP-03206","title":"Substance P activates Mas-related G protein-coupled receptors to induce itch.","authors":"Azimi, Ehsan; Reddy, Vemuri B; Pereira, Paula Juliana Seadi; Talbot, Sebastien; Woolf, Clifford J; Lerner, Ethan A","year":2017,"journal":"The Journal of allergy and clinical immunology, 140(2), 447-453.e3","doi":"10.1016/j.jaci.2016.12.980","pmid":"28219706","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Substance P induces scratching behavior and activates dorsal root ganglion neurons through Mas-related G protein-coupled receptors (Mrgprs), specifically MrgprA1, rather than through the neurokinin-1 receptor (NK-1R).","whyItMatters":"Understanding that Substance P induces itch via Mrgprs rather than NK-1R opens new pathways for developing targeted treatments for itch and related inflammatory conditions.","specificNumbers":"","methodology":"The study used genetic knockout mice and pharmacological inhibitors to assess the role of Mrgprs and NK-1R in Substance P-induced scratching behavior and neuronal activation in cultured dorsal root ganglion neurons.","limitations":"The study was conducted in mice and in vitro neuron cultures, so further research is needed to confirm if the findings fully translate to humans."},{"rthcId":"RPEP-03207","title":"Atractylodin Induces Myosin Light Chain Phosphorylation and Promotes Gastric Emptying through Ghrelin Receptor.","authors":"Bai, Yu; Zhao, Yan-Hua; Xu, Jian-Ya; Yu, Xi-Zhong; Hu, Yun-Xia; Zhao, Zhi-Qiang","year":2017,"journal":"Evidence-based complementary and alternative medicine : eCAM, 2017, 2186798","doi":"10.1155/2017/2186798","pmid":"28883883","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Atractylodin activates the growth hormone secretagogue receptor (GHSR) in human gastric smooth muscle cells, increasing intracellular calcium and promoting phosphorylation of myosin light chain (MLC), which enhances muscle contraction. In mice, atractylodin administration increased MLC phosphorylation in the gastric antrum and accelerated gastric emptying via GHSR activation.","whyItMatters":"Understanding how atractylodin stimulates stomach muscle contraction through the ghrelin receptor offers potential for developing new treatments for digestive disorders involving delayed gastric emptying and muscle dysfunction.","specificNumbers":"","methodology":"The study used human gastric smooth muscle cells to test atractylodin's effect on calcium levels and MLC phosphorylation, comparing it to a known ghrelin receptor agonist. Additionally, mice were treated with atractylodin to assess gastric emptying rates and MLC phosphorylation in stomach tissues.","limitations":"The study was conducted primarily in cell cultures and mice, so results may not fully translate to humans. The study type and evidence strength were not specified, limiting assessment of reliability."},{"rthcId":"RPEP-03208","title":"Substance P NK1 receptor in the rat corpus callosum during postnatal development.","authors":"Barbaresi, Paolo; Mensà, Emanuela; Bastioli, Guendalina; Amoroso, Salvatore","year":2017,"journal":"Brain and behavior, 7(6), e00713","doi":"10.1002/brb3.713","pmid":"28638718","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"NK1-immunopositive neurons (NK1IP-n) in the rat corpus callosum first appear at postnatal day 5, increase significantly in number by day 10, then slightly decline by day 30. Their size and dendritic complexity increase over this period, and their distribution pattern resembles that of adults from day 5 onward. Unlike other intracallosal neurons, NK1IP-n persist in significant numbers into adulthood, indicating potential roles in axon myelination and pathfinding.","whyItMatters":"Understanding the development of NK1 receptor neurons in the corpus callosum helps clarify their role in brain wiring and myelination, which are critical for proper neural communication and may inform research on neurological development and disorders.","specificNumbers":"","methodology":"The study used immunocytochemistry to detect NK1 receptor-expressing neurons in the rat corpus callosum at multiple postnatal time points from day 0 to day 30. Neuronal number, size, distribution, and morphology were analyzed to track developmental changes.","limitations":"The study does not specify functional experiments to directly link NK1IP-n to myelination or axon pathfinding, and the evidence strength and study type are not clearly defined, limiting conclusions about causality."},{"rthcId":"RPEP-03209","title":"Substance P in the anterior thalamic paraventricular nucleus: promotion of ethanol drinking in response to orexin from the hypothalamus.","authors":"Barson, Jessica R; Poon, Kinning; Ho, Hui Tin; Alam, Mohammad I; Sanzalone, Lilia; Leibowitz, Sarah F","year":2017,"journal":"Addiction biology, 22(1), 58-69","doi":"10.1111/adb.12288","pmid":"26223289","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Substance P in the anterior paraventricular nucleus of the thalamus (aPVT) stimulates intermittent-access ethanol drinking in rats, similar to orexin. Blocking the neurokinin 1 receptor (NK1R), the receptor for substance P, in the aPVT reduces ethanol drinking. Orexin increases substance P expression in the aPVT, and the effect of orexin on ethanol drinking is blocked by NK1R antagonists, indicating that substance P mediates orexin’s stimulatory effect on alcohol intake.","whyItMatters":"Understanding how substance P and orexin interact to promote alcohol drinking could reveal new targets for treating alcohol use disorders. This insight into brain mechanisms controlling alcohol intake may help develop more effective therapies.","specificNumbers":"","methodology":"The study used rat models to examine the effects of substance P and orexin in specific subregions of the paraventricular nucleus of the thalamus on ethanol drinking behavior. Researchers administered substance P, orexin, and NK1R antagonists locally in the brain and measured changes in ethanol and sucrose consumption. Molecular analyses assessed substance P mRNA and peptide levels following orexin administration.","limitations":"The study was conducted in rats, so findings may not fully translate to humans. The exact study design and sample size were not detailed, limiting assessment of evidence strength."},{"rthcId":"RPEP-03210","title":"Inhibition of substance P-induced defensive behavior via neurokinin-1 receptor antagonism in the central and medial but not basolateral nuclei of the amygdala in male Wistar rats.","authors":"Bassi, G S; Carvalho, M C; Almada, R C; Brandão, M L","year":2017,"journal":"Progress in neuro-psychopharmacology & biological psychiatry, 77, 146-154","doi":"10.1016/j.pnpbp.2017.03.026","pmid":"28390968","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Substance P injections in the central (CeA) and medial (MeA) amygdala nuclei induced anxiogenic-like (fear-related) effects, with NK-1 receptor antagonism reducing these effects in CeA but not MeA. Antinociceptive effects were observed only in the MeA via NK-1 receptor activation. No effects were noted in the basolateral amygdala (BLA).","whyItMatters":"Understanding how substance P and NK-1 receptors in specific amygdala regions regulate fear and pain responses can guide development of targeted treatments for anxiety and pain disorders.","specificNumbers":"","methodology":"The study used microinjections of substance P and the NK-1 receptor antagonist spantide into three amygdala nuclei (CeA, MeA, BLA) of male Wistar rats. Behavioral tests included the elevated plus maze for anxiety, tail-flick test for pain response, and ultrasonic vocalization recordings.","limitations":"The study was conducted only in male rats, limiting generalizability. The exact mechanisms in the medial amygdala remain unclear since NK-1 antagonism did not block anxiogenic effects there."},{"rthcId":"RPEP-03211","title":"Prospects of In vivo Incorporation of Non-canonical Amino Acids for the Chemical Diversification of Antimicrobial Peptides.","authors":"Baumann, Tobias; Nickling, Jessica H; Bartholomae, Maike; Buivydas, Andrius; Kuipers, Oscar P; Budisa, Nediljko","year":2017,"journal":"Frontiers in microbiology, 8, 124","doi":"10.3389/fmicb.2017.00124","pmid":"28210246","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In vivo incorporation of non-canonical amino acids into ribosomally synthesized antimicrobial peptides enables significant chemical diversification, enhancing properties such as pH and protease resistance, solubility, oral availability, and circulation half-life. This method expands the chemical space of antimicrobial peptides beyond natural limits, offering new avenues for drug development.","whyItMatters":"This approach could help overcome antibiotic resistance by creating novel antimicrobial peptides with enhanced stability and effectiveness, addressing a critical need in infectious disease treatment.","specificNumbers":"","methodology":"The study reviews current methods for residue- and site-specific incorporation of non-canonical amino acids into antimicrobial peptides produced recombinantly in bacterial hosts. It compares ribosomally synthesized peptides with those produced by solid phase peptide synthesis to highlight the potential of non-canonical amino acid introduction.","limitations":"The study is a perspective and review rather than experimental research, so practical large-scale production challenges and clinical efficacy remain to be fully addressed."},{"rthcId":"RPEP-03212","title":"Infant milk fat droplet size and coating affect postprandial responses in healthy adult men: a proof-of-concept study.","authors":"Baumgartner, S; van de Heijning, B J M; Acton, D; Mensink, R P","year":2017,"journal":"European journal of clinical nutrition, 71(9), 1108-1113","doi":"10.1038/ejcn.2017.50","pmid":"28422122","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The experimental infant milk formula (Concept IMF) with larger, phospholipid-coated fat droplets resulted in faster absorption of fats and carbohydrates, evidenced by earlier peaks in plasma glucose and insulin concentrations compared to the control formula. However, overall postprandial lipid and amino acid responses were similar between formulas.","whyItMatters":"Understanding how fat droplet size and coating affect digestion can help improve infant formulas to better mimic human milk, potentially enhancing nutrient absorption and metabolic responses in infants.","specificNumbers":"","methodology":"A randomized, double-blind, crossover study was conducted with 29 healthy adult men aged 18-25 years. Participants consumed two different infant milk formulas on separate occasions, and blood samples were collected over 5 hours to measure postprandial metabolic responses.","limitations":"The study was conducted in healthy adult men rather than infants, limiting direct applicability to infant digestion. The sample size was relatively small, and long-term effects were not assessed."},{"rthcId":"RPEP-03213","title":"Lung ischemia reperfusion injury: the therapeutic role of dipeptidyl peptidase 4 inhibition.","authors":"Beckers, Paul A J; Gielis, Jan F; Van Schil, Paul E; Adriaensen, Dirk","year":2017,"journal":"Annals of translational medicine, 5(6), 129","doi":"10.21037/atm.2017.01.41","pmid":"28462209","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"DPP4 inhibition shows potential as a therapeutic target to reduce lung ischemia-reperfusion injury by modulating inflammatory responses and oxidative stress. The protective effects may involve substrates like GLP-1, VIP, and SDF-1α activating MAPK and PI3K/Akt pathways.","whyItMatters":"Understanding DPP4's role in lung injury could lead to new treatments for acute lung damage after ischemia-reperfusion events, improving outcomes in lung transplantation and other clinical scenarios.","specificNumbers":"","methodology":"This is a review article summarizing current research on the role of DPP4 and its inhibition in lung ischemia-reperfusion injury, drawing on studies of molecular mechanisms and related signaling pathways.","limitations":"As a review, it does not present new experimental data and the evidence strength and study types are not specified, limiting conclusions about clinical efficacy."},{"rthcId":"RPEP-03214","title":"The anti-migraine component of butterbur extracts, isopetasin, desensitizes peptidergic nociceptors by acting on TRPA1 cation channel.","authors":"Benemei, Silvia; De Logu, Francesco; Li Puma, Simone; Marone, Ilaria Maddalena; Coppi, Elisabetta; Ugolini, Filippo; Liedtke, Wolfgang; Pollastro, Federica; Appendino, Giovanni; Geppetti, Pierangelo; Materazzi, Serena; Nassini, Romina","year":2017,"journal":"British journal of pharmacology, 174(17), 2897-2911","doi":"10.1111/bph.13917","pmid":"28622417","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Isopetasin activates TRPA1 channels on peptidergic nociceptors, leading to their desensitization and reduced neuropeptide release, which likely underlies the anti-migraine effects of butterbur extracts.","whyItMatters":"Understanding how isopetasin modulates TRPA1 channels provides insight into natural migraine treatments and could guide development of new therapies targeting pain pathways.","specificNumbers":"","methodology":"The study used single-cell calcium imaging and patch-clamp recordings in human and rodent TRPA1-expressing cells, neurogenic motor response tests in rodent bladders, CGRP release assays from mouse spinal cords, and behavioral and vascular responses in mice and rats following isopetasin exposure.","limitations":"The study was conducted primarily in vitro and in animal models, so human clinical efficacy and safety require further investigation."},{"rthcId":"RPEP-03215","title":"Intranasal oxytocin enhances intrinsic corticostriatal functional connectivity in women.","authors":"Bethlehem, R A I; Lombardo, M V; Lai, M-C; Auyeung, B; Crockford, S K; Deakin, J; Soubramanian, S; Sule, A; Kundu, P; Voon, V; Baron-Cohen, S","year":2017,"journal":"Translational psychiatry, 7(4), e1099","doi":"10.1038/tp.2017.72","pmid":"28418398","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Intranasal oxytocin administration in women significantly enhanced resting-state functional connectivity between corticostriatal networks involved in reward, emotion, social communication, language, and pain processing, with an effect size of 1.39 standard deviations above placebo. This connectivity increase correlated with higher autistic traits.","whyItMatters":"Understanding how oxytocin affects brain connectivity in women can guide future research on social and emotional disorders, including autism, and help tailor treatments based on individual traits.","specificNumbers":"","methodology":"A double-blind, placebo-controlled crossover design was used with 26 typically developing women. Resting-state fMRI data were collected 40 minutes after intranasal oxytocin or placebo administration. Independent components analysis assessed connectivity changes, and gene expression analysis of oxytocin receptors was performed on brain tissue data.","limitations":"The sample size was relatively small and limited to typically developing women, which may reduce generalizability. The study did not include men or clinical populations, and the evidence strength is not clearly established."},{"rthcId":"RPEP-03216","title":"Occurrence of nausea, vomiting and diarrhoea reported as adverse events in clinical trials studying glucagon-like peptide-1 receptor agonists: A systematic analysis of published clinical trials.","authors":"Bettge, Karolin; Kahle, Melanie; Abd El Aziz, Mirna S; Meier, Juris J; Nauck, Michael A","year":2017,"journal":"Diabetes, obesity & metabolism, 19(3), 336-347","doi":"10.1111/dom.12824","pmid":"27860132","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GI side effects from GLP-1 receptor agonists are dose-dependent: higher doses cause more nausea (p=0.0017 across all agents) and diarrhea (p=0.031). Adding metformin as background treatment significantly worsened nausea (p=0.04) and vomiting (p=0.0009). Long-acting GLP-1 drugs (like liraglutide, dulaglutide, exenatide weekly) caused less nausea and vomiting than short-acting ones (like exenatide twice daily), but caused more diarrhea. Among long-acting agents, albiglutide and exenatide weekly had less nausea than liraglutide, while dulaglutide was similar to liraglutide.","whyItMatters":"GI side effects are the number-one reason people stop taking GLP-1 drugs. This systematic analysis gives doctors and patients a clearer picture of which specific drugs cause the most nausea, vomiting, and diarrhea — and shows that dose, background medications, and duration of action all matter. It helps guide prescribing decisions, especially for patients already on metformin or those who are sensitive to nausea.","specificNumbers":"","methodology":"The researchers searched PubMed for phase 3 clinical trials of GLP-1 receptor agonists and selected 32 trials. They systematically compared the proportion of patients reporting nausea, vomiting, or diarrhea across different drugs, doses, and background medications. They calculated relative risks with 95% confidence intervals, using exenatide twice daily as the reference for short-acting agents and liraglutide as the reference for long-acting agents.","limitations":"This was a systematic analysis of published trial data, not a meta-analysis of individual patient data. The comparison across trials is limited by differences in study populations, trial design, and reporting methods. Adverse event reporting in clinical trials can undercount real-world side effects. The analysis did not include newer agents like semaglutide or tirzepatide."},{"rthcId":"RPEP-03217","title":"Temperature and ion dual responsive biphenyl-dipeptide supramolecular hydrogels as extracellular matrix mimic-scaffolds for cell culture applications.","authors":"Bian, Shaoquan; Cai, Hanxu; Cui, Yani; He, Mengmeng; Cao, Wanxu; Chen, Xuening; Sun, Yong; Liang, Jie; Fan, Yujiang; Zhang, Xingdong","year":2017,"journal":"Journal of materials chemistry. B, 5(20), 3667-3674","doi":"10.1039/c7tb00576h","pmid":"32264055","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Biphenylacetic acid-diphenylalanine (BPAA-FF) forms homogeneous, transparent hydrogels via temperature or ion triggers, which effectively support L929 cell adhesion and proliferation in both 2D and 3D cultures under physiological conditions.","whyItMatters":"Developing hydrogels that mimic the extracellular matrix and respond to physiological stimuli is crucial for creating better scaffolds for tissue engineering and regenerative therapies.","specificNumbers":"","methodology":"The study synthesized several BPAA-dipeptide compounds using solid phase peptide synthesis and evaluated their gelation behavior under temperature changes and ion addition. Cell culture experiments with L929 fibroblasts assessed the hydrogels' ability to support cell growth.","limitations":"The study focuses on a limited set of dipeptides and cell types; further research is needed to confirm biocompatibility and functionality across diverse cells and in vivo models."},{"rthcId":"RPEP-03218","title":"Ghrelin suppresses cholecystokinin (CCK), peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) in the intestine, and attenuates the anorectic effects of CCK, PYY and GLP-1 in goldfish (Carassius auratus).","authors":"Blanco, Ayelén Melisa; Bertucci, Juan Ignacio; Valenciano, Ana Isabel; Delgado, María Jesús; Unniappan, Suraj","year":2017,"journal":"Hormones and behavior, 93, 62-71","doi":"10.1016/j.yhbeh.2017.05.004","pmid":"28506816","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Ghrelin suppresses the intestinal expression and protein levels of the anorectic hormones CCK, PYY, and GLP-1 in goldfish. This suppression is mediated via the ghrelin receptor GHS-R1a and results in attenuation of the appetite-reducing effects of these peptides.","whyItMatters":"Understanding how ghrelin interacts with appetite-suppressing hormones in fish provides insight into the regulation of feeding and energy balance, which can inform broader peptide research and potential applications in aquaculture or metabolic studies.","specificNumbers":"","methodology":"The study used immunohistochemistry to localize hormones and receptors in goldfish intestines, intestinal explant cultures to measure gene and protein expression changes after ghrelin treatment, and in vivo intraperitoneal co-administration of peptides to assess effects on food intake.","limitations":"The study was conducted in goldfish, so findings may not directly translate to other species. The evidence strength and study type were not specified, limiting assessment of robustness."},{"rthcId":"RPEP-03219","title":"Endogenous Opiates and Behavior: 2015.","authors":"Bodnar, Richard J","year":2017,"journal":"Peptides, 88, 126-188","doi":"10.1016/j.peptides.2016.12.004","pmid":"28012859","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The 2015 research collectively demonstrates that endogenous opioid peptides and their receptors play critical roles in modulating a wide range of behaviors and physiological functions, including pain, stress responses, addiction, learning, and various organ systems.","whyItMatters":"Understanding how natural opioids regulate behavior and physiology helps guide peptide research and therapeutic development for pain, addiction, and mental health disorders.","specificNumbers":"","methodology":"This is an annual review article summarizing multiple studies published in 2015 that investigated molecular, pharmacological, and genetic manipulations of endogenous opioid peptides and receptors and their behavioral effects.","limitations":"As a review, it depends on the quality and scope of the original studies and does not present new experimental data."},{"rthcId":"RPEP-03220","title":"Saliva-Derived Host Defense Peptides Histatin1 and LL-37 Increase Secretion of Antimicrobial Skin and Oral Mucosa Chemokine CCL20 in an IL-1α-Independent Manner.","authors":"Boink, Mireille A; Roffel, Sanne; Nazmi, Kamran; Bolscher, Jan G M; Veerman, Enno C I; Gibbs, Susan","year":2017,"journal":"Journal of immunology research, 2017, 3078194","doi":"10.1155/2017/3078194","pmid":"28815185","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Saliva-derived host defense peptides LL-37 and Histatin1 significantly increase secretion of the antimicrobial chemokine CCL20 by keratinocyte-fibroblast cocultures from skin and oral mucosa. This CCL20 secretion occurs independently of IL-1α signaling, unlike other proinflammatory cytokines and chemokines which were IL-1α dependent.","whyItMatters":"Understanding how saliva peptides stimulate antimicrobial chemokine production helps reveal natural defense mechanisms in skin and oral tissues. This knowledge can inform development of new treatments to enhance innate immunity and prevent infections.","specificNumbers":"","methodology":"The study used cocultures of keratinocytes and fibroblasts from skin and oral mucosa exposed to the peptides LL-37 and Histatin1. Secretion levels of chemokines and cytokines including CCL20, CCL2, CXCL1, CXCL8, CCL27, IL-1α, and IL-6 were measured to assess inflammatory and antimicrobial responses.","limitations":"The study does not specify in vivo effects or clinical relevance, and the exact signaling pathways for IL-1α independent CCL20 secretion remain unclear. The study type and evidence strength were not detailed."},{"rthcId":"RPEP-03221","title":"Role of hemokinin-1 in health and disease.","authors":"Borbély, Éva; Helyes, Zsuzsanna","year":2017,"journal":"Neuropeptides, 64, 9-17","doi":"10.1016/j.npep.2016.12.003","pmid":"27993375","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"HK-1, encoded by the Tac4 gene, is uniquely expressed in blood cells and has diverse physiological and pathological roles distinct from substance P despite sharing the NK1 receptor. It may act through an unidentified receptor, indicating novel signaling pathways.","whyItMatters":"Understanding HK-1's unique actions could lead to new biomarkers and therapies for conditions involving pain, inflammation, immune regulation, and cancer, expanding peptide-based medical approaches.","specificNumbers":"","methodology":"This article is a review summarizing clinical and experimental studies on HK-1 expression and function over 16 years, comparing it with substance P and exploring its biological roles and therapeutic potential.","limitations":"The review notes limited clinical data and incomplete understanding of HK-1's receptor and signaling pathways, highlighting the need for further research."},{"rthcId":"RPEP-03222","title":"Dermasence refining gel modulates pathogenetic factors of rosacea in vitro.","authors":"Borelli, C; Becker, B; Thude, S; Fehrenbacher, B; Isermann, D","year":2017,"journal":"Journal of cosmetic dermatology, 16(4), e31-e36","doi":"10.1111/jocd.12323","pmid":"28349651","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Treatment with Dermasence Refining Gel significantly reduced the expression of CAMP (LL-37 gene) by 4.19-fold and VEGFA by 2.55-fold, as well as decreased PAR2 expression by 1.33-fold, while increasing KLK5 expression by 2.06-fold in an in vitro human epidermis model after 18 hours. The reduction in CAMP expression was statistically significant (P<.01).","whyItMatters":"Understanding how Dermasence Refining Gel modulates inflammatory factors offers scientific support for its use as a topical treatment for rosacea, potentially improving symptom management with over-the-counter products.","specificNumbers":"","methodology":"The study used an in vitro model of human reconstituted epidermis to analyze the effect of Dermasence Refining Gel on the expression of rosacea-related proteins KLK5, LL-37 (CAMP), PAR2, and VEGF. Protein levels were measured by fluorescence intensity after 18 hours of treatment compared to controls.","limitations":"The study was conducted in vitro using reconstructed human epidermis, which may not fully replicate the complex environment of human skin in vivo. Clinical trials are needed to confirm efficacy and safety in patients."},{"rthcId":"RPEP-03223","title":"Endogenous Antimicrobial Peptide Expression in Response to Bacterial Epidermal Colonization.","authors":"Brandwein, Michael; Bentwich, Zvi; Steinberg, Doron","year":2017,"journal":"Frontiers in immunology, 8, 1637","doi":"10.3389/fimmu.2017.01637","pmid":"29230218","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The skin expresses antimicrobial peptides both constitutively (always on) and in response to pathogenic microbial stimuli. These AMPs are differentially effective against various bacterial and fungal skin colonizers — meaning different peptides target different microbes.\n\nCommensal bacterial colonization of the skin is vital for training and maintaining both innate and adaptive immune functions. The skin's AMP defense works alongside its physical barrier to prevent pathogen colonization. The review identifies a gap between descriptive disease-state studies and single-species in vitro experiments, calling for research that better mimics natural skin conditions.","whyItMatters":"Understanding the skin's natural antimicrobial peptide defenses is essential for developing treatments for skin infections, eczema, acne, and other dermatological conditions where the microbe-host balance is disrupted. Rather than relying solely on antibiotics, future therapies could harness or boost the skin's own peptide defenses to restore healthy microbial balance.","specificNumbers":"","methodology":"This is a literature review that compiled and analyzed published studies on cutaneous antimicrobial peptide expression in response to microbial colonization. The review covers both in vitro studies of individual AMPs against specific microbes and descriptive studies of AMP expression in various skin conditions.","limitations":"As a narrative review, findings depend on the quality and scope of underlying studies. Most AMP studies use simplified in vitro conditions (single bacterial species) that don't reflect the complex, multi-species environment of real skin. Direct clinical trial data on therapeutic AMP use for skin conditions is limited. The review was published in 2017, before many recent advances in skin microbiome characterization."},{"rthcId":"RPEP-03224","title":"JMV2894, a novel growth hormone secretagogue, accelerates body mass recovery in an experimental model of cachexia.","authors":"Bresciani, Elena; Rizzi, Laura; Molteni, Laura; Ravelli, Monica; Liantonio, Antonella; Ben Haj Salah, Khoubaib; Fehrentz, Jean-Alain; Martinez, Jean; Omeljaniuk, Robert J; Biagini, Giuseppe; Locatelli, Vittorio; Torsello, Antonio","year":2017,"journal":"Endocrine, 58(1), 106-114","doi":"10.1007/s12020-016-1184-2","pmid":"27896546","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"JMV2894 significantly accelerated body weight recovery in cisplatin-treated rats compared to other growth hormone secretagogues, restoring weight to control levels by the end of the study. It reduced muscle wasting markers without promoting fat accumulation.","whyItMatters":"Cachexia severely impacts cancer patients' quality of life and treatment outcomes. Finding peptides like JMV2894 that can counteract weight loss without adverse fat gain offers a promising therapeutic approach.","specificNumbers":"","methodology":"Adult rats were treated with cisplatin to induce weight loss, then given either vehicle or one of three growth hormone secretagogues (hexarelin, JMV2894, JMV2951) over 12 days. Body weight and food intake were monitored daily, and muscle and fat tissue analyses were conducted.","limitations":"The study was conducted in rats, so results may not fully translate to humans. The sample size and detailed dosing information were not specified, limiting assessment of robustness."},{"rthcId":"RPEP-03225","title":"Abnormalities in substance P neurokinin-1 receptor binding in key brainstem nuclei in sudden infant death syndrome related to prematurity and sex.","authors":"Bright, Fiona M; Vink, Robert; Byard, Roger W; Duncan, Jhodie R; Krous, Henry F; Paterson, David S","year":2017,"journal":"PloS one, 12(9), e0184958","doi":"10.1371/journal.pone.0184958","pmid":"28931039","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"SIDS cases exhibited significantly decreased neurokinin-1 receptor (NK1R) binding in critical medullary nuclei including the nucleus tractus solitarii and subdivisions of the inferior olivo-cerebellar complex. These abnormalities were influenced by prematurity and male sex, potentially explaining increased SIDS risk in these groups.","whyItMatters":"Understanding the neurochemical abnormalities in brainstem regions controlling vital functions may help explain SIDS mechanisms and identify at-risk infants. It highlights the role of substance P signaling in infant respiratory and cardiovascular regulation.","specificNumbers":"","methodology":"The study used [125I] Bolton Hunter substance P autoradiography to measure NK1R binding density in 13 medullary nuclei from brainstem tissue of 55 SIDS and 21 control infants. Binding differences were analyzed with respect to developmental profiles, prematurity, and sex.","limitations":"The study design and evidence strength are not specified, and causality cannot be established. The sample size, while reasonable, may limit generalizability. The exact functional consequences of altered NK1R binding require further investigation."},{"rthcId":"RPEP-03226","title":"Temporally controlled growth factor delivery from a self-assembling peptide hydrogel and electrospun nanofibre composite scaffold.","authors":"Bruggeman, Kiara F; Wang, Yi; Maclean, Francesca L; Parish, Clare L; Williams, Richard J; Nisbet, David R","year":2017,"journal":"Nanoscale, 9(36), 13661-13669","doi":"10.1039/c7nr05004f","pmid":"28876347","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The composite scaffold combining self-assembling peptide (SAP) hydrogel and electrospun nanofibres achieved temporally controlled growth factor release, with an initial burst from the hydrogel over 12 hours and a delayed, sustained release from nanofibres starting 6 days later. This dual-phase delivery system mimics extracellular matrix nanofibre sizes and maintains injectable hydrogel properties.","whyItMatters":"Controlled timing of growth factor delivery is crucial for effective tissue regeneration, as different healing stages require different signals. This scaffold design offers a promising approach to improve regenerative medicine therapies by providing tailored delivery profiles.","specificNumbers":"","methodology":"Researchers created a two-component scaffold by mixing short electrospun nanofibres with tissue-specific SAP hydrogel. Both components were separately loaded with growth factors. Release profiles were measured to assess timing and duration of growth factor delivery from each material.","limitations":"The study does not specify in vivo efficacy or long-term biocompatibility data, and the exact growth factors used and their clinical relevance were not detailed. The study type and evidence strength are not clearly defined."},{"rthcId":"RPEP-03227","title":"Clinical Pharmacokinetics and Pharmacodynamics of Albiglutide.","authors":"Brønden, Andreas; Knop, Filip K; Christensen, Mikkel B","year":2017,"journal":"Clinical pharmacokinetics, 56(7), 719-731","doi":"10.1007/s40262-016-0499-8","pmid":"28050889","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Albiglutide demonstrated a 0.8-1.0% placebo-corrected reduction in glycosylated hemoglobin (HbA1c) and a 1.3-2.4 mmol/L reduction in fasting plasma glucose in clinical trials. It has a half-life of 5 days allowing for once-weekly subcutaneous dosing and shows a favorable safety profile with fewer gastrointestinal side effects than liraglutide but a slight increase in pancreatitis risk.","whyItMatters":"Understanding albiglutide's properties helps optimize treatment for type 2 diabetes, offering a convenient once-weekly option with manageable side effects and effective blood sugar control.","specificNumbers":"","methodology":"This article reviews pharmacokinetic and pharmacodynamic data from clinical trials, including the HARMONY trial program, which assessed efficacy and safety of albiglutide in patients with type 2 diabetes.","limitations":"Long-term cardiovascular safety data were pending at the time of publication, and the exact risk-benefit profile requires further clarification from ongoing trials."},{"rthcId":"RPEP-03228","title":"Orexin activation counteracts decreases in nonexercise activity thermogenesis (NEAT) caused by high-fat diet.","authors":"Bunney, P E; Zink, A N; Holm, A A; Billington, C J; Kotz, C M","year":2017,"journal":"Physiology & behavior, 176, 139-148","doi":"10.1016/j.physbeh.2017.03.040","pmid":"28363838","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03229","title":"Harnessing glucagon-like peptide-1 receptor agonists for the pharmacological treatment of overweight and obesity.","authors":"Burcelin, R; Gourdy, P","year":2017,"journal":"Obesity reviews : an official journal of the International Association for the Study of Obesity, 18(1), 86-98","doi":"10.1111/obr.12465","pmid":"27636208","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 receptor agonists target the gut-brain axis to regulate appetite and promote weight loss. Liraglutide 3.0 mg was approved for obesity treatment in adults with BMI ≥27 kg/m² and comorbidities. The review covers how GLP-1 — a peptide naturally produced in the gut — coordinates appetite regulation through brain signaling, and how pharmacological GLP-1 RAs amplify these effects to produce clinically meaningful weight loss. Other GLP-1 RAs were identified as promising future obesity treatments.","whyItMatters":"This review captures a pivotal moment in obesity medicine — the transition from having almost no effective pharmacological treatments to the emergence of GLP-1 receptor agonists as a viable drug class. By explaining how gut-derived peptides regulate the brain's appetite centers, it laid the groundwork for the GLP-1 drug revolution that has since transformed obesity treatment with drugs like semaglutide and tirzepatide.","specificNumbers":"Liraglutide 3.0 mg approved dose · BMI ≥27 kg/m² with comorbidities · 30+ years of rising global obesity · review covers gut-brain axis peptide signaling · multiple GLP-1 RAs discussed","methodology":"This is a narrative review summarizing the role of the gut-brain axis in appetite regulation, the biology of GLP-1 peptide signaling, the mechanism of action of GLP-1 receptor agonists for weight loss, and clinical trial data supporting their use in obesity management.","limitations":"Published before the explosive growth of GLP-1 RA use for obesity, this review covers primarily liraglutide data. Semaglutide for obesity and tirzepatide were not yet approved or fully studied. Long-term outcome data and real-world effectiveness were limited at the time. The review does not address the now-recognized cardiovascular benefits of GLP-1 RAs."},{"rthcId":"RPEP-03230","title":"Human microglia and astrocytes constitutively express the neurokinin-1 receptor and functionally respond to substance P.","authors":"Burmeister, Amanda R; Johnson, M Brittany; Chauhan, Vinita S; Moerdyk-Schauwecker, Megan J; Young, Ada D; Cooley, Ian D; Martinez, Alejandra N; Ramesh, Geeta; Philipp, Mario T; Marriott, Ian","year":2017,"journal":"Journal of neuroinflammation, 14(1), 245","doi":"10.1186/s12974-017-1012-5","pmid":"29237453","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Human microglia and astrocytes constitutively express robust levels of the full-length neurokinin-1 receptor (NK-1R) isoform. Bacterial pathogens further elevated NK-1R expression in astrocytes. Substance P activated NF-κB signaling in microglia and augmented inflammatory cytokine release and neurotoxic mediator production by astrocytes in response to bacterial pathogens.\n\nThese findings were confirmed across multiple systems: nonhuman primate brain explants, primary human microglia and astrocytes, and immortalized human glial cell lines, using RT-PCR, immunoblotting, immunofluorescence, flow cytometry, ELISA, and neuronal toxicity assays. Previous work by the same group showed NK-1R antagonists could limit neuroinflammatory damage in bacterial meningitis models.","whyItMatters":"Bacterial meningitis can cause devastating brain damage, much of it from the body's own inflammatory response rather than the bacteria themselves. This study identifies the substance P/NK-1R pathway as a key amplifier of this damaging neuroinflammation. Since NK-1R antagonists (substance P blockers) already exist as approved drugs for other conditions, there's a clear path toward repurposing them to protect the brain during severe infections.","specificNumbers":"","methodology":"Researchers used multiple complementary techniques — RT-PCR, immunoblot analysis, immunofluorescent microscopy, and flow cytometry — to characterize NK-1R expression in nonhuman primate brain tissue, primary human microglia and astrocytes, and immortalized human glial cell lines. Functional responses to substance P were assessed through NF-κB nuclear translocation analysis, ELISA for inflammatory cytokines, and neuronal cell toxicity assays following exposure to bacterial pathogens.","limitations":"All experiments were conducted in vitro or ex vivo using cell cultures and brain tissue explants, not in living patients. The exact downstream signaling pathways beyond NF-κB were not fully mapped. The study focused on bacterial infections and may not generalize to viral or autoimmune neuroinflammation. No clinical trial of NK-1R antagonists for meningitis has been conducted."},{"rthcId":"RPEP-03231","title":"Combination SGLT2 inhibitor and GLP-1 receptor agonist therapy: a complementary approach to the treatment of type 2 diabetes.","authors":"Busch, Robert S; Kane, Michael P","year":2017,"journal":"Postgraduate medicine, 129(7), 686-697","doi":"10.1080/00325481.2017.1342509","pmid":"28657399","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The combination therapy of exenatide (a GLP-1 receptor agonist) and dapagliflozin (an SGLT2 inhibitor) over 28 weeks led to significantly greater reductions in glycated hemoglobin, body weight, and systolic blood pressure compared to either drug alone in patients with type 2 diabetes.","whyItMatters":"Combining these two drug classes targets multiple organs and disease mechanisms in type 2 diabetes, potentially improving patient outcomes beyond blood sugar control alone, which is important for reducing cardiovascular risks.","specificNumbers":"","methodology":"This review summarizes clinical trial data, including the largest trial (DURATION-8) involving 685 patients with type 2 diabetes treated for 28 weeks with combined exenatide and dapagliflozin or monotherapy, assessing effects on glycemic control, weight, and cardiovascular risk factors.","limitations":"The review is based on available clinical trial data up to 2017, with limited long-term safety and efficacy data for combination therapy; the study type and evidence strength are not clearly defined."},{"rthcId":"RPEP-03232","title":"Differential stability of therapeutic peptides with different proteolytic cleavage sites in blood, plasma and serum.","authors":"Böttger, Roland; Hoffmann, Ralf; Knappe, Daniel","year":2017,"journal":"PloS one, 12(6), e0178943","doi":"10.1371/journal.pone.0178943","pmid":"28575099","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03233","title":"Body weight loss, effective satiation and absence of homeostatic neuropeptide compensation in male Sprague Dawley rats schedule fed a protein crosslinked diet.","authors":"Cassie, Nikki; Anderson, Richard L; Wilson, Dana; Pawsey, Anne; Mercer, Julian G; Barrett, Perry","year":2017,"journal":"Appetite, 117, 234-246","doi":"10.1016/j.appet.2017.06.029","pmid":"28687371","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Protein crosslinking of a milk-protein based diet in rats led to reduced caloric intake and body weight loss, particularly lean and fat tissue, without typical compensatory increases in hypothalamic neuropeptides Npy and Agrp. Hormonal responses such as GLP-1, leptin, and insulin were attenuated or absent in rats fed liquid or crosslinked diets compared to solid diets.","whyItMatters":"Understanding how food structure affects appetite regulation and metabolism can guide development of diets that promote weight loss and metabolic health without triggering compensatory hunger mechanisms.","specificNumbers":"","methodology":"Male Sprague Dawley rats were schedule fed modified AIN-93M diets in three forms: liquid, protein-crosslinked soft-solid, and solid. Food intake, body composition, circulating hormones, and hypothalamic neuropeptide expression were measured to assess satiation, satiety, and metabolic responses.","limitations":"The study was conducted in male rats, so results may not directly translate to humans. The exact mechanisms by which protein crosslinking alters neuropeptide and hormonal responses remain unclear."},{"rthcId":"RPEP-03234","title":"GLP-1 and GLP-2 Levels are Correlated with Satiety Regulation After Roux-en-Y Gastric Bypass: Results of an Exploratory Prospective Study.","authors":"Cazzo, Everton; Pareja, José Carlos; Chaim, Elinton Adami; Geloneze, Bruno; Barreto, Maria Rita Lazzarini; Magro, Daniéla Oliveira","year":2017,"journal":"Obesity surgery, 27(3), 703-708","doi":"10.1007/s11695-016-2345-3","pmid":"27565666","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03235","title":"Peptide-22 and Cyclic RGD Functionalized Liposomes for Glioma Targeting Drug Delivery Overcoming BBB and BBTB.","authors":"Chen, Cuitian; Duan, Ziqing; Yuan, Yan; Li, Ruixiang; Pang, Liang; Liang, Jianming; Xu, Xinchun; Wang, Jianxin","year":2017,"journal":"ACS applied materials & interfaces, 9(7), 5864-5873","doi":"10.1021/acsami.6b15831","pmid":"28128553","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03236","title":"Preparation and bioavailability of calcium-chelating peptide complex from tilapia skin hydrolysates.","authors":"Chen, Jun; Qiu, Xujian; Hao, Gengxin; Zhang, Meng; Weng, Wuyin","year":2017,"journal":"Journal of the science of food and agriculture, 97(14), 4898-4903","doi":"10.1002/jsfa.8363","pmid":"28390071","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The calcium-chelating peptide complex (CPC) from tilapia skin hydrolysates outperformed calcium carbonate on multiple bone-related measures in calcium-deficient mice after 4 weeks of feeding. Mice receiving CPC showed significantly greater femur length, femur weight, bone calcium content, hydroxyproline content (a marker of collagen), calcium absorption, and body weight gain compared to CaCO3-fed mice.\n\nInterestingly, serum biochemistry and bone mineral density showed no significant differences between the two groups — the improvements were specifically in bone structure, composition, and calcium uptake. Structural analysis confirmed that calcium ions bind to the peptides through NH and CN groups, creating a stable chelate complex with molecular weights mainly between 180 and 2000 Da.","whyItMatters":"Calcium supplements are among the most widely used dietary supplements worldwide, but standard calcium salts like calcium carbonate are poorly absorbed by many people. Using food-derived peptides to chelate calcium could improve bioavailability while also providing amino acids for collagen synthesis. This approach also adds value to fish processing waste — tilapia skin would otherwise be discarded.","specificNumbers":"","methodology":"Researchers hydrolyzed tilapia skin to produce small peptides, then chelated calcium ions to these peptides to create the CPC. They characterized the complex using scanning electron microscopy and infrared spectroscopy. For the biological test, calcium-deficient mice were fed either CPC or calcium carbonate for 4 weeks, then evaluated for serum markers, bone mineral density, femur measurements, calcium content, collagen markers, and calcium absorption.","limitations":"This was an animal study in mice, so results may not directly translate to humans. The sample size was not reported in the abstract. The 4-week duration is relatively short for bone outcomes. The study compared CPC only to calcium carbonate, not to other enhanced calcium formulations (like calcium citrate or calcium with vitamin D). Serum biochemistry and bone mineral density did not differ, raising questions about the clinical significance of the structural bone improvements."},{"rthcId":"RPEP-03237","title":"Nanofiber-based sutures induce endogenous antimicrobial peptide.","authors":"Chen, Shixuan; Ge, Liangpeng; Gombart, Adrian F; Shuler, Franklin D; Carlson, Mark A; Reilly, Debra A; Xie, Jingwei","year":2017,"journal":"Nanomedicine (London, England), 12(21), 2597-2609","doi":"10.2217/nnm-2017-0161","pmid":"28960168","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03238","title":"Designer D-form self-assembling peptide scaffolds promote the proliferation and migration of rat bone marrow-derived mesenchymal stem cells.","authors":"Chen, Shuo; Zhou, Ao; He, Bin; Zhao, Weikang; Chen, Xiaojun; Jiang, Dianming","year":2017,"journal":"International journal of molecular medicine, 40(3), 679-688","doi":"10.3892/ijmm.2017.3056","pmid":"28677805","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03239","title":"Preparation and functional evaluation of collagen oligopeptide-rich hydrolysate from fish skin with the serine collagenolytic protease from Pseudoalteromonas sp. SM9913.","authors":"Chen, Xiu-Lan; Peng, Ming; Li, Jing; Tang, Bai-Lu; Shao, Xuan; Zhao, Fang; Liu, Chang; Zhang, Xi-Ying; Li, Ping-Yi; Shi, Mei; Zhang, Yu-Zhong; Song, Xiao-Yan","year":2017,"journal":"Scientific reports, 7(1), 15716","doi":"10.1038/s41598-017-15971-9","pmid":"29146927","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03240","title":"Azapeptide Synthesis Methods for Expanding Side-Chain Diversity for Biomedical Applications.","authors":"Chingle, Ramesh; Proulx, Caroline; Lubell, William D","year":2017,"journal":"Accounts of chemical research, 50(7), 1541-1556","doi":"10.1021/acs.accounts.7b00114","pmid":"28598597","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03241","title":"Peptide Pharmacological Approaches to Treating Traumatic Brain Injury: a Case for Arginine-Rich Peptides.","authors":"Chiu, Li Shan; Anderton, Ryan S; Knuckey, Neville W; Meloni, Bruno P","year":2017,"journal":"Molecular neurobiology, 54(10), 7838-7857","doi":"10.1007/s12035-016-0287-3","pmid":"27844291","tags":[],"studyType":"review","evidenceStrength":"low","keyFinding":"This review examines peptide-based approaches to treating traumatic brain injury, highlighting arginine-rich peptides as a particularly promising new class of neuroprotective agents. While traditional single-action drugs and combination therapies have failed in TBI clinical trials, arginine-rich cationic peptides appear to work through multiple neuroprotective mechanisms simultaneously.\n\nThese peptides have already shown protective effects against ischemic stroke in animal models, providing a reasonable basis to investigate their potential in TBI. The review argues that arginine-rich peptides' ability to target multiple injury cascades at once may make them better suited to TBI's complex pathophysiology than conventional drugs.","whyItMatters":"Traumatic brain injury affects millions of people annually and currently has no effective neuroprotective drug treatment — only surgery and rehabilitation. The repeated failure of single-target drugs in TBI trials has been one of neuroscience's most frustrating challenges. Arginine-rich peptides represent a fundamentally different approach: instead of targeting one mechanism, they appear to intervene at multiple points in the brain damage cascade, potentially overcoming the complexity that has defeated previous treatments.","specificNumbers":"No specific trial numbers — this is a narrative review of the field","methodology":"This is a narrative review article that examines previously published research on peptide-based treatments for TBI. The authors surveyed the literature on various peptides tested in TBI models, with particular focus on cationic arginine-rich peptides and their mechanisms of neuroprotection.","limitations":"As a review article, this paper does not present new experimental data. The case for arginine-rich peptides in TBI is largely based on preclinical animal studies and extrapolation from stroke research. No clinical trial results in TBI patients are discussed, and the translation from animal models to human TBI has historically been extremely challenging."},{"rthcId":"RPEP-03242","title":"Hepatitis C may enhance key amplifiers of psoriasis.","authors":"Chun, K; Afshar, M; Audish, D; Kabigting, F; Paik, A; Gallo, R; Hata, T","year":2017,"journal":"Journal of the European Academy of Dermatology and Venereology : JEADV, 31(4), 672-678","doi":"10.1111/jdv.13578","pmid":"27184185","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03243","title":"Self-Healing, Self-Assembled β-Sheet Peptide-Poly(γ-glutamic acid) Hybrid Hydrogels.","authors":"Clarke, David E; Pashuck, E Thomas; Bertazzo, Sergio; Weaver, Jonathan V M; Stevens, Molly M","year":2017,"journal":"Journal of the American Chemical Society, 139(21), 7250-7255","doi":"10.1021/jacs.7b00528","pmid":"28525280","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The hybrid hydrogels achieved mechanical properties spanning 10-200 kPa by varying β-sheet peptide graft density and concentration — covering the stiffness range of many soft tissues. The non-covalent β-sheet cross-links provided a critical advantage: after being strained to failure, the hydrogels self-healed, recovering all of their original storage moduli in most cases.\n\nSpectroscopic analysis confirmed the presence of β-sheet secondary structure within the hydrogels, verifying that the peptide cross-links maintained their intended architecture. Only 15% functionalization of the polymer's repeating units with β-sheet peptides was needed to form a gel, leaving the remaining sites available for incorporating biological epitopes for cell signaling or tissue-specific functionality.","whyItMatters":"Injectable self-healing hydrogels could transform regenerative medicine by filling tissue defects through minimally invasive injection, then reforming after any damage from the injection process. The ability to tune stiffness across an order of magnitude means a single platform can be optimized for different tissues — from soft brain tissue (~1 kPa) to muscle and cartilage (~100+ kPa). The available functionalization sites on the polymer backbone make this a versatile platform for adding cell-binding peptides, growth factors, or drug-release capabilities.","specificNumbers":"","methodology":"The researchers synthesized poly(γ-glutamic acid) polymers and grafted self-assembling β-sheet peptides at varying densities. Hydrogel formation and mechanical properties were characterized using rheology (measuring stiffness, elasticity, and self-healing behavior after strain failure). Secondary structure was verified using spectroscopic techniques (likely circular dichroism and FTIR). Scanning electron microscopy was used to visualize gel microstructure. The graft density and concentration were systematically varied to map the relationship between peptide content and mechanical properties.","limitations":"The study focuses on material characterization without biological testing — no cell culture, biocompatibility, or in vivo experiments were reported. The self-healing was demonstrated under laboratory conditions; behavior in a biological environment with enzymes, immune cells, and dynamic loading may differ. The 10-200 kPa range, while useful for soft tissues, doesn't reach the stiffness needed for bone or tendon applications. Degradation rate and long-term stability were not characterized. The cost and scalability of peptide-polymer synthesis for clinical manufacturing were not addressed."},{"rthcId":"RPEP-03244","title":"Phase I Randomized Placebo-controlled, Double-blind Study of the Safety and Tolerability of Bremelanotide Coadministered With Ethanol in Healthy Male and Female Participants.","authors":"Clayton, Anita H; Lucas, Johna; DeRogatis, Leonard R; Jordan, Robert","year":2017,"journal":"Clinical therapeutics, 39(3), 514-526.e14","doi":"10.1016/j.clinthera.2017.01.018","pmid":"28189361","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03245","title":"Role of orexin-A in the ventrolateral preoptic area on components of total energy expenditure.","authors":"Coborn, J E; DePorter, D P; Mavanji, V; Sinton, C M; Kotz, C M; Billington, C J; Teske, J A","year":2017,"journal":"International journal of obesity (2005), 41(8), 1256-1262","doi":"10.1038/ijo.2017.92","pmid":"28392556","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03246","title":"Evaluation of a melanocortin-4 receptor (MC4R) agonist (Setmelanotide) in MC4R deficiency.","authors":"Collet, Tinh-Hai; Dubern, Béatrice; Mokrosinski, Jacek; Connors, Hillori; Keogh, Julia M; Mendes de Oliveira, Edson; Henning, Elana; Poitou-Bernert, Christine; Oppert, Jean-Michel; Tounian, Patrick; Marchelli, Florence; Alili, Rohia; Le Beyec, Johanne; Pépin, Dominique; Lacorte, Jean-Marc; Gottesdiener, Andrew; Bounds, Rebecca; Sharma, Shubh; Folster, Cathy; Henderson, Bart; O'Rahilly, Stephen; Stoner, Elizabeth; Gottesdiener, Keith; Panaro, Brandon L; Cone, Roger D; Clément, Karine; Farooqi, I Sadaf; Van der Ploeg, Lex H T","year":2017,"journal":"Molecular metabolism, 6(10), 1321-1329","doi":"10.1016/j.molmet.2017.06.015","pmid":"29031731","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03247","title":"Emerging Roles of Kisspeptin in Sexual and Emotional Brain Processing.","authors":"Comninos, Alexander N; Dhillo, Waljit S","year":2017,"journal":"Neuroendocrinology, 106(2), 195-202","doi":"10.1159/000479326","pmid":"28866668","tags":["neuropeptides"],"studyType":"review","evidenceStrength":"n/a (review)","keyFinding":"Review consolidating evidence that kisspeptin enhances limbic brain activity to sexual stimuli, reduces negative mood, and modulates brain responses to attraction cues, expanding its role beyond reproductive axis regulation.","whyItMatters":"Establishes kisspeptin as a potential therapeutic target for psychosexual disorders, bridging reproductive endocrinology and emotional/sexual brain processing.","specificNumbers":"","methodology":"Narrative review of preclinical and clinical kisspeptin research.","limitations":"Review article. Most human data from a single research group."},{"rthcId":"RPEP-03248","title":"Kisspeptin modulates sexual and emotional brain processing in humans.","authors":"Comninos, Alexander N; Wall, Matthew B; Demetriou, Lysia; Shah, Amar J; Clarke, Sophie A; Narayanaswamy, Shakunthala; Neber, Asija; Bloom, Stuart R; Filbey, Francis M; Dhillo, Waljit S","year":2017,"journal":"The Journal of clinical investigation, 127(2), 709-719","doi":"10.1172/JCI89519","pmid":"28011402","tags":["neuropeptides"],"studyType":"human-rct","evidenceStrength":"moderate","keyFinding":"Kisspeptin enhanced limbic brain activity (amygdala, cingulate, globus pallidus, thalamus, putamen) specifically in response to sexual stimuli in 29 healthy men, while also reducing negative mood.","whyItMatters":"First evidence in humans that kisspeptin modulates sexual brain processing through limbic pathways, linking reproductive hormones to emotional brain function.","specificNumbers":"29 healthy men; enhanced activity in amygdala, cingulate, globus pallidus, posterior thalamus, putamen; specific to sexual stimuli","methodology":"Double-blind, placebo-controlled, 2-way crossover fMRI study in 29 healthy heterosexual men receiving kisspeptin-54 or saline infusion.","limitations":"Male participants only. Single session. IV infusion not reflecting physiological kisspeptin release patterns."},{"rthcId":"RPEP-03249","title":"Antimicrobial peptide-gold nanoscale therapeutic formulation with high skin regenerative potential.","authors":"Comune, Michela; Rai, Akhilesh; Chereddy, Kiran K; Pinto, Sandra; Aday, Sezin; Ferreira, André F; Zonari, Alessandra; Blersch, Josephine; Cunha, Rodrigo; Rodrigues, Ricardo; Lerma, Juan; Simões, Pedro N; Préat, Veronique; Ferreira, Lino","year":2017,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 262, 58-71","doi":"10.1016/j.jconrel.2017.07.007","pmid":"28694030","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03250","title":"Autoantigens ADAMTSL5 and LL37 are significantly upregulated in active Psoriasis and localized with keratinocytes, dendritic cells and other leukocytes.","authors":"Fuentes-Duculan, Judilyn; Bonifacio, Kathleen M; Hawkes, Jason E; Kunjravia, Norma; Cueto, Inna; Li, Xuan; Gonzalez, Juana; Garcet, Sandra; Krueger, James G","year":2017,"journal":"Experimental dermatology, 26(11), 1075-1082","doi":"10.1111/exd.13378","pmid":"28482118","tags":[],"studyType":"basic-research","evidenceStrength":"moderate","keyFinding":"The antimicrobial peptide LL37 (cathelicidin) and the protein ADAMTSL5 — both identified as psoriasis autoantigens — were significantly upregulated in active psoriatic skin lesions (P < 0.05). Both were co-expressed by dendritic cells, macrophages, and some T cells in the dermis.\n\nCritically, both ADAMTSL5 and LL37 were significantly reduced by IL-17 blockade and TNF-α blockade (etanercept), suggesting a feed-forward loop: the inflammatory cytokines that drive psoriasis also drive production of the autoantigens that trigger it. LL37 gene expression was significantly upregulated in lesional skin and significantly downregulated following etanercept treatment.","whyItMatters":"Understanding why the immune system attacks the skin in psoriasis has been a major research question. This study shows that LL37 — a peptide originally known for its antimicrobial function — acts as an autoantigen that drives psoriatic inflammation, and that this process feeds on itself through a cytokine loop. The fact that existing biologic treatments (anti-TNF, anti-IL-17) reduce these autoantigens helps explain why these drugs work and suggests that directly targeting LL37 could be another therapeutic strategy.","specificNumbers":"ADAMTSL5 and LL37 significantly increased in lesional skin (P < 0.05) · both decreased by IL-17 and TNF-α blockade · LL37 downregulated by etanercept · psoriasis affects 2–4% of North Americans and Europeans","methodology":"Immunohistochemistry and two-color immunofluorescence were performed on non-lesional and lesional psoriasis skin biopsies to characterize ADAMTSL5 and LL37 expression and their co-localization with T cells, dendritic cells, neutrophils, and macrophages. Gene expression analysis was used to measure LL37 levels before and after biologic treatment.","limitations":"This is a tissue-based observational study that demonstrates correlation but not direct causation between autoantigen expression and disease activity. The exact sample size of skin biopsies is not specified in the abstract. The study does not determine whether LL37 or ADAMTSL5 is the primary driver of the autoimmune response. Results from skin biopsies may not capture the full complexity of systemic psoriatic inflammation."},{"rthcId":"RPEP-03251","title":"Peptide modulators of Rac1/Tiam1 protein-protein interaction: An alternative approach for cardiovascular diseases.","authors":"Contini, Alessandro; Ferri, Nicola; Bucci, Raffaella; Lupo, Maria Giovanna; Erba, Emanuela; Gelmi, Maria Luisa; Pellegrino, Sara","year":2017,"journal":"Biopolymers","doi":"10.1002/bip.23089","pmid":"29178143","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03252","title":"Interspecies cathelicidin comparison reveals divergence in antimicrobial activity, TLR modulation, chemokine induction and regulation of phagocytosis.","authors":"Coorens, Maarten; Scheenstra, Maaike R; Veldhuizen, Edwin J A; Haagsman, Henk P","year":2017,"journal":"Scientific reports, 7, 40874","doi":"10.1038/srep40874","pmid":"28102367","tags":["antimicrobial-peptides","cathelicidins"],"studyType":"in-vitro-study","evidenceStrength":"moderate","keyFinding":"Comparing 12 cathelicidins from 6 different species under identical lab conditions revealed that these antimicrobial peptides differ significantly in their functions — both between species and within the same species. Most cathelicidins killed E. coli and/or MRSA effectively, but a surprising finding emerged: under more realistic physiological conditions, antimicrobial activity against E. coli dropped for nearly all cathelicidins while activity against MRSA actually increased.\n\nSeven of 12 cathelicidins could neutralize bacterial LPS (a toxin from gram-negative bacteria), and 7 could neutralize LTA (from gram-positive bacteria), but there was no correlation between the two abilities. Only 4 of 12 enhanced DNA-induced TLR9 activation, showing that immune-modulating functions are not universal across cathelicidins.","whyItMatters":"Most antimicrobial peptide research focuses on just two cathelicidins — human LL-37 and mouse CRAMP — and assumes findings apply broadly. This study shows that's a dangerous assumption: cathelicidins vary widely in what they can do. This matters for drug development because it means researchers can't simply pick any cathelicidin and expect the same results, and it opens the door to choosing specific cathelicidins for specific therapeutic applications.","specificNumbers":"12 cathelicidins · 6 species · 7/12 neutralized LPS · 7/12 neutralized LTA · 4/12 enhanced TLR9 activation · tested against E. coli and MRSA","methodology":"Researchers tested 12 cathelicidin peptides from 6 animal species under standardized conditions to enable direct comparison. They measured antimicrobial activity against E. coli and MRSA, tested the ability to neutralize bacterial toxins (LPS and LTA), assessed TLR modulation, chemokine induction, and phagocytosis regulation. Tests were conducted both in standard lab conditions and under more physiologically relevant conditions.","limitations":"This is an in-vitro study using cell cultures and bacterial assays. How these functional differences translate to real infections in living animals or humans is unknown. The study tested antimicrobial activity against only two bacterial species. The physiological conditions used, while more realistic than standard lab conditions, still don't fully replicate the complexity of a living immune system."},{"rthcId":"RPEP-03253","title":"Eighteen Months of Treatment With Subcutaneous Abaloparatide Followed by 6 Months of Treatment With Alendronate in Postmenopausal Women With Osteoporosis: Results of the ACTIVExtend Trial.","authors":"Cosman, Felicia; Miller, Paul D; Williams, Gregory C; Hattersley, Gary; Hu, Ming-Yi; Valter, Ivo; Fitzpatrick, Lorraine A; Riis, Bente Juel; Christiansen, Claus; Bilezikian, John P; Black, Dennis","year":2017,"journal":"Mayo Clinic proceedings, 92(2), 200-210","doi":"10.1016/j.mayocp.2016.10.009","pmid":"28160873","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03254","title":"Detection and in vitro metabolism of the confiscated peptides BPC 157 and MGF R23H.","authors":"Cox, Holly D; Miller, Geoff D; Eichner, Daniel","year":2017,"journal":"Drug testing and analysis, 9(10), 1490-1498","doi":"10.1002/dta.2152","pmid":"28035768","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03255","title":"Understanding the Role of Serotonin in Female Hypoactive Sexual Desire Disorder and Treatment Options.","authors":"Croft, Harry A","year":2017,"journal":"The journal of sexual medicine, 14(12), 1575-1584","doi":"10.1016/j.jsxm.2017.10.068","pmid":"29198512","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03256","title":"The cellular and molecular bases of leptin and ghrelin resistance in obesity.","authors":"Cui, Huxing; López, Miguel; Rahmouni, Kamal","year":2017,"journal":"Nature reviews. Endocrinology, 13(6), 338-351","doi":"10.1038/nrendo.2016.222","pmid":"28232667","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Leptin resistance and ghrelin resistance are both hallmarks of obesity and operate through distinct but interconnected cellular mechanisms. Leptin resistance involves impaired signaling through the JAK-STAT pathway in hypothalamic neurons, while ghrelin resistance involves disrupted cAMP signaling. Both forms of resistance contribute to a dysfunctional energy homeostasis system that perpetuates weight gain.\n\nThe review identifies several molecular targets within these resistance pathways that could potentially be exploited for pharmacological intervention in obesity treatment.","whyItMatters":"Understanding hormone resistance is central to solving the obesity epidemic. Many people assume weight gain is simply about willpower, but this review shows that obesity fundamentally alters the brain's hormonal communication system. By mapping the specific molecular breakdowns, researchers can identify precise targets for new anti-obesity drugs — potentially ones that restore hormone sensitivity rather than just mimicking or replacing these signals.","specificNumbers":"","methodology":"This is a narrative review article published in Nature Reviews Endocrinology. The authors synthesized findings from animal studies, cell biology experiments, and clinical observations to provide a comprehensive overview of leptin and ghrelin resistance mechanisms in obesity.","limitations":"As a review article, this paper synthesizes existing research rather than presenting new experimental data. Much of the mechanistic evidence comes from animal models (particularly rodents), which may not fully reflect human physiology. The review was published in 2017, so more recent discoveries about hormone resistance pathways may not be included."},{"rthcId":"RPEP-03257","title":"Proteins and bioactive peptides from donkey milk: The molecular basis for its reduced allergenic properties.","authors":"Cunsolo, Vincenzo; Saletti, Rosaria; Muccilli, Vera; Gallina, Serafina; Di Francesco, Antonella; Foti, Salvatore","year":2017,"journal":"Food research international (Ottawa, Ont.), 99(Pt 1), 41-57","doi":"10.1016/j.foodres.2017.07.002","pmid":"28784499","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03258","title":"Renal sodium handling and blood pressure changes in gestational protein-restricted offspring: Role of renal nerves and ganglia neurokinin expression.","authors":"Custódio, Augusto H; de Lima, Marcelo C; Vaccari, Bárbara; Boer, Patrícia A; Gontijo, José A R","year":2017,"journal":"PloS one, 12(6), e0179499","doi":"10.1371/journal.pone.0179499","pmid":"28632750","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03259","title":"Liraglutide in an Adolescent Population with Obesity: A Randomized, Double-Blind, Placebo-Controlled 5-Week Trial to Assess Safety, Tolerability, and Pharmacokinetics of Liraglutide in Adolescents Aged 12-17 Years.","authors":"Danne, Thomas; Biester, Torben; Kapitzke, Kerstin; Jacobsen, Sanja H; Jacobsen, Lisbeth V; Petri, Kristin C Carlsson; Hale, Paula M; Kordonouri, Olga","year":2017,"journal":"The Journal of pediatrics, 181, 146-153.e3","doi":"10.1016/j.jpeds.2016.10.076","pmid":"27979579","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03260","title":"Neuropeptide Y expression confers benzo[a]pyrene induced anxiolytic like behavioral response during early adolescence period of male Wistar rats.","authors":"Das, Saroj Kumar; Patri, Manorama","year":2017,"journal":"Neuropeptides, 61, 23-30","doi":"10.1016/j.npep.2016.07.001","pmid":"27402563","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03261","title":"Cathelicidin augments VDR-dependent anti-leishmanial immune response in Indian Post-Kala-Azar Dermal Leishmaniasis.","authors":"Das, Sushmita; Sardar, Abul Hasan; Abhishek, Kumar; Kumar, Ajay; Rabidas, Vidya Nand; Das, Pradeep","year":2017,"journal":"International immunopharmacology, 50, 130-138","doi":"10.1016/j.intimp.2017.06.010","pmid":"28662432","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03262","title":"Epitope-Specific Immunotherapy Targeting CD4-Positive T Cells in Celiac Disease: Safety, Pharmacokinetics, and Effects on Intestinal Histology and Plasma Cytokines with Escalating Dose Regimens of Nexvax2 in a Randomized, Double-Blind, Placebo-Controlled Phase 1 Study.","authors":"Daveson, A James M; Ee, Hooi C; Andrews, Jane M; King, Timothy; Goldstein, Kaela E; Dzuris, John L; MacDougall, James A; Williams, Leslie J; Treohan, Anita; Cooreman, Michael P; Anderson, Robert P","year":2017,"journal":"EBioMedicine, 26, 78-90","doi":"10.1016/j.ebiom.2017.11.018","pmid":"29191561","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03263","title":"Cyclotides as Tools in Chemical Biology.","authors":"de Veer, Simon J; Weidmann, Joachim; Craik, David J","year":2017,"journal":"Accounts of chemical research, 50(7), 1557-1565","doi":"10.1021/acs.accounts.7b00157","pmid":"28644007","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03264","title":"Hypoxia-Related Hormonal Appetite Modulation in Humans during Rest and Exercise: Mini Review.","authors":"Debevec, Tadej","year":2017,"journal":"Frontiers in physiology, 8, 366","doi":"10.3389/fphys.2017.00366","pmid":"28611686","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03265","title":"Mouse Hemokinin-1 Decapeptide Subjected to a Brain-specific Post-translational Modification.","authors":"Deliconstantinos, Georgia; Barton, Stephen; Soloviev, Mikhail; Page, Nigel","year":2017,"journal":"In vivo (Athens, Greece), 31(5), 991-998","doi":null,"pmid":"28882971","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03266","title":"Pharmacokinetics and pharmacodynamics of PF-05190457: The first oral ghrelin receptor inverse agonist to be profiled in healthy subjects.","authors":"Denney, William S; Sonnenberg, Gabriele E; Carvajal-Gonzalez, Santos; Tuthill, Theresa; Jackson, V Margaret","year":2017,"journal":"British journal of clinical pharmacology, 83(2), 326-338","doi":"10.1111/bcp.13127","pmid":"27621150","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03267","title":"Partial Sleep Deprivation Reduces the Efficacy of Orexin-A to Stimulate Physical Activity and Energy Expenditure.","authors":"DePorter, Danielle P; Coborn, Jamie E; Teske, Jennifer A","year":2017,"journal":"Obesity (Silver Spring, Md.), 25(10), 1716-1722","doi":"10.1002/oby.21944","pmid":"28815952","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03268","title":"Phage Selection of Cyclic Peptides for Application in Research and Drug Development.","authors":"Deyle, Kaycie; Kong, Xu-Dong; Heinis, Christian","year":2017,"journal":"Accounts of chemical research, 50(8), 1866-1874","doi":"10.1021/acs.accounts.7b00184","pmid":"28719188","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03269","title":"Validation and characterization of a novel method for selective vagal deafferentation of the gut.","authors":"Diepenbroek, Charlene; Quinn, Danielle; Stephens, Ricky; Zollinger, Benjamin; Anderson, Seth; Pan, Annabelle; de Lartigue, Guillaume","year":2017,"journal":"American journal of physiology. Gastrointestinal and liver physiology, 313(4), G342-G352","doi":"10.1152/ajpgi.00095.2017","pmid":"28705805","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03270","title":"Influences of Dietary Added Sugar Consumption on Striatal Food-Cue Reactivity and Postprandial GLP-1 Response.","authors":"Dorton, Hilary M; Luo, Shan; Monterosso, John R; Page, Kathleen A","year":2017,"journal":"Frontiers in psychiatry, 8, 297","doi":"10.3389/fpsyt.2017.00297","pmid":"29403396","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03271","title":"Celecoxib-induced gastrointestinal, liver and brain lesions in rats, counteraction by BPC 157 or L-arginine, aggravation by L-NAME.","authors":"Drmic, Domagoj; Kolenc, Danijela; Ilic, Spomenko; Bauk, Lara; Sever, Marko; Zenko Sever, Anita; Luetic, Kresimir; Suran, Jelena; Seiwerth, Sven; Sikiric, Predrag","year":2017,"journal":"World journal of gastroenterology, 23(29), 5304-5312","doi":"10.3748/wjg.v23.i29.5304","pmid":"28839430","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03272","title":"Expression of hypothalamic neurohormones and their receptors in the human eye.","authors":"Dubovy, Sander R; Fernandez, Maria P; Echegaray, Jose J; Block, Norman L; Unoki, Noriyuki; Perez, Roberto; Vidaurre, Irving; Lee, Richard K; Nadji, Mehrdad; Schally, Andrew V","year":2017,"journal":"Oncotarget, 8(40), 66796-66814","doi":"10.18632/oncotarget.18358","pmid":"28977997","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03273","title":"Stable gastric pentadecapeptide BPC 157 in the treatment of colitis and ischemia and reperfusion in rats: New insights.","authors":"Duzel, Antonija; Vlainic, Josipa; Antunovic, Marko; Malekinusic, Dominik; Vrdoljak, Borna; Samara, Mariam; Gojkovic, Slaven; Krezic, Ivan; Vidovic, Tinka; Bilic, Zdenko; Knezevic, Mario; Sever, Marko; Lojo, Nermin; Kokot, Antonio; Kolovrat, Marijan; Drmic, Domagoj; Vukojevic, Jaksa; Kralj, Tamara; Kasnik, Katarina; Siroglavic, Marko; Seiwerth, Sven; Sikiric, Predrag","year":2017,"journal":"World journal of gastroenterology, 23(48), 8465-8488","doi":"10.3748/wjg.v23.i48.8465","pmid":"29358856","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03274","title":"Chronic heart failure as a state of reduced effectiveness of the natriuretic peptide system: implications for therapy.","authors":"Díez, Javier","year":2017,"journal":"European journal of heart failure, 19(2), 167-176","doi":"10.1002/ejhf.656","pmid":"27766748","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies three major mechanisms for natriuretic peptide system failure in chronic heart failure: (1) reduced availability of biologically active BNP due to increased processing into inactive forms, (2) diminished target organ responsiveness to NPs, and (3) overstimulation of counter-regulatory systems (RAAS, sympathetic nervous system, and endothelin-1) that overpower NP effects.\n\nSacubitril/valsartan addresses this by simultaneously inhibiting neprilysin (the enzyme that degrades NPs) and blocking angiotensin receptors (countering RAAS activation). Clinical data show this combination increases NP levels and their intracellular mediator cGMP, suggesting genuine restoration of NP system effectiveness — translating into reduced mortality and morbidity.","whyItMatters":"Heart failure affects over 60 million people worldwide and remains a leading cause of death. Understanding why the body's own protective peptide system fails in advanced heart failure is crucial for developing better treatments. This review provides the mechanistic rationale for sacubitril/valsartan (Entresto), which has become a standard-of-care treatment — explaining not just that it works, but why it works at the peptide level.","specificNumbers":"","methodology":"This is a narrative review synthesizing evidence from clinical studies of exogenous NP administration in heart failure patients, mechanistic research on NP metabolism and receptor function, and clinical trial data on neprilysin inhibitors and sacubitril/valsartan (particularly the PARADIGM-HF trial).","limitations":"As a single-author narrative review, there is no systematic search methodology or formal quality assessment of cited studies. The review was published in 2017, before long-term real-world data on sacubitril/valsartan fully matured. Some of the mechanistic explanations for NP system failure remain partially theoretical, particularly regarding BNP processing abnormalities."},{"rthcId":"RPEP-03275","title":"Clarifying the Ghrelin System's Ability to Regulate Feeding Behaviours Despite Enigmatic Spatial Separation of the GHSR and Its Endogenous Ligand.","authors":"Edwards, Alexander; Abizaid, Alfonso","year":2017,"journal":"International journal of molecular sciences, 18(4)","doi":"10.3390/ijms18040859","pmid":"28422060","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03276","title":"Treatment with grass allergen peptides improves symptoms of grass pollen-induced allergic rhinoconjunctivitis.","authors":"Ellis, Anne K; Frankish, Charles W; O'Hehir, Robyn E; Armstrong, Kristen; Steacy, Lisa; Larché, Mark; Hafner, Roderick P","year":2017,"journal":"The Journal of allergy and clinical immunology, 140(2), 486-496","doi":"10.1016/j.jaci.2016.11.043","pmid":"28236469","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03277","title":"Prospect of rindopepimut in the treatment of glioblastoma.","authors":"Elsamadicy, Aladine A; Chongsathidkiet, Pakawat; Desai, Rupen; Woroniecka, Karolina; Farber, S Harrison; Fecci, Peter E; Sampson, John H","year":2017,"journal":"Expert opinion on biological therapy, 17(4), 507-513","doi":"10.1080/14712598.2017.1299705","pmid":"28274144","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03278","title":"UVB irradiation induces rapid changes in galanin, substance P and c-fos immunoreactivity in rat dorsal root ganglia and spinal cord.","authors":"Etemadi, Leila; Pettersson, Lina M E; Danielsen, Nils","year":2017,"journal":"Peptides, 87, 71-83","doi":"10.1016/j.peptides.2016.12.001","pmid":"27923581","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"UVB irradiation of the rat heel rapidly altered neuropeptide levels in pain-processing areas. Galanin-positive neurons in the dorsal root ganglia (DRG) decreased significantly at most time points (2-96h), while galanin immunoreactivity increased in the spinal cord dorsal horn, central canal area, and lateral spinal nucleus from 12-96h. Substance P levels in DRG neurons remained unchanged, but substance P immunoreactivity increased in the dorsal spinal cord at 48h. The neuronal activation marker c-fos appeared in the dorsal horn and central canal area at 24-48h — the same timeframe when hyperalgesia peaks. Skin blood flow nearly doubled 24h after irradiation.","whyItMatters":"Sunburn-induced pain (UVB hyperalgesia) is a well-established model for studying inflammatory pain that translates between rats and humans. This study shows that two neuropeptides — galanin and substance P — are rapidly redistributed in the pain-processing nervous system after UV exposure, peaking at the same time as heightened pain sensitivity. Understanding which neuropeptides drive sunburn pain could lead to better pain treatments and reveals fundamental mechanisms of how tissue inflammation is communicated to the spinal cord.","specificNumbers":"Skin blood flow: ~2-fold increase at 24h · Galanin: decreased in DRG (2-96h), increased in spinal cord (12-96h) · Substance P: increased in dorsal spinal cord at 48h · c-fos: dorsal horn + central canal at 24-48h · L5 spinal level","methodology":"Rats received UVB irradiation to the heel area. At time points ranging from 2 to 96 hours post-exposure, dorsal root ganglia and spinal cord tissue at the L5 level were collected and analyzed by immunohistochemistry for galanin, substance P, and c-fos expression. Skin blood flow was measured using laser Doppler to confirm the inflammatory response.","limitations":"This is a rat study — the neuropeptide response timing and distribution may differ in humans. Only the L5 spinal level was analyzed, so changes at other spinal levels could have been missed. Immunohistochemistry shows protein distribution but doesn't distinguish between newly synthesized peptide and peptide that has been transported from elsewhere. The functional significance of the lateral spinal nucleus changes (an unusual finding) is unclear."},{"rthcId":"RPEP-03279","title":"Twin-screw extruded lipid implants containing TRP2 peptide for tumour therapy.","authors":"Even, Marie-Paule; Bobbala, Sharan; Gibson, Blake; Hook, Sarah; Winter, Gerhard; Engert, Julia","year":2017,"journal":"European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 114, 79-87","doi":"10.1016/j.ejpb.2016.12.033","pmid":"28104440","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03280","title":"Structure and Function of Small Non-Peptide CRF Antagonists and their Potential Clinical Use.","authors":"Fahmy, Hesham; Kuppast, Bhimanna; Ismail, Mohamed Teleb","year":2017,"journal":"Current molecular pharmacology, 10(4), 270-281","doi":"10.2174/1874467209666161101144155","pmid":"27809751","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03281","title":"Pharmacological approaches to cardio-renal syndrome: a role for the inodilator levosimendan.","authors":"Fedele, Francesco; Karason, Kristjan; Matskeplishvili, Simon","year":2017,"journal":"European heart journal supplements : journal of the European Society of Cardiology, 19(Suppl C), C22-C28","doi":"10.1093/eurheartj/sux002","pmid":"29249907","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03282","title":"Effect of Natriuretic Peptide-Guided Therapy on Hospitalization or Cardiovascular Mortality in High-Risk Patients With Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial.","authors":"Felker, G Michael; Anstrom, Kevin J; Adams, Kirkwood F; Ezekowitz, Justin A; Fiuzat, Mona; Houston-Miller, Nancy; Januzzi, James L; Mark, Daniel B; Piña, Ileana L; Passmore, Gayle; Whellan, David J; Yang, Hongqiu; Cooper, Lawton S; Leifer, Eric S; Desvigne-Nickens, Patrice; O'Connor, Christopher M","year":2017,"journal":"JAMA, 318(8), 713-720","doi":"10.1001/jama.2017.10565","pmid":"28829876","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03283","title":"Relaxin and insulin-like peptide 3 in the musculoskeletal system: from bench to bedside.","authors":"Ferlin, Alberto; De Toni, Luca; Sandri, Marco; Foresta, Carlo","year":2017,"journal":"British journal of pharmacology, 174(10), 1015-1024","doi":"10.1111/bph.13490","pmid":"27059798","tags":["relaxin","insulin-like-peptides"],"studyType":"Narrative Review","evidenceStrength":"low-moderate","keyFinding":"Relaxin and insulin-like peptide 3 (INSL3) — two peptide hormones traditionally associated with pregnancy and testicular function — appear to play important roles in bone and muscle health. Relaxin is involved in bone remodeling (balancing bone formation and breakdown), helps heal injured ligaments, and promotes skeletal muscle regeneration. INSL3, a male-specific hormone from testicular Leydig cells, also participates in bone remodeling.\n\nBoth peptides may help explain sex differences in osteoporosis and sarcopenia risk, and could represent new therapeutic targets for musculoskeletal diseases.","whyItMatters":"Osteoporosis and sarcopenia (age-related muscle loss) affect hundreds of millions of people worldwide. Current treatments are limited. If relaxin and INSL3 genuinely influence bone and muscle health, they could open entirely new therapeutic avenues — particularly for age-related musculoskeletal decline and for understanding why men and women experience these conditions differently.","specificNumbers":"Review article — no primary experimental data presented","methodology":"This is a narrative review synthesizing published preclinical and clinical evidence on relaxin and INSL3 in the musculoskeletal system. The authors examined cell culture studies, animal models, and available clinical data to build a case for these peptides' roles in bone remodeling, ligament healing, and muscle regeneration.","limitations":"As a narrative review, this does not present new experimental data. Much of the evidence comes from animal models and cell studies — clinical evidence in humans is still limited. The review is part of a themed journal section on relaxin family peptides, which may introduce selection bias toward positive findings. No systematic search methodology is described."},{"rthcId":"RPEP-03284","title":"The Antifungal Activity of Lactoferrin and Its Derived Peptides: Mechanisms of Action and Synergy with Drugs against Fungal Pathogens.","authors":"Fernandes, Kenya E; Carter, Dee A","year":2017,"journal":"Frontiers in microbiology, 8, 2","doi":"10.3389/fmicb.2017.00002","pmid":"28149293","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03285","title":"Structure-activity relationship for peptídic growth hormone secretagogues.","authors":"Ferro, P; Krotov, G; Zvereva, I; Rodchenkov, G; Segura, J","year":2017,"journal":"Drug testing and analysis, 9(1), 87-95","doi":"10.1002/dta.1947","pmid":"26811125","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03286","title":"GABA, Selank, and Olanzapine Affect the Expression of Genes Involved in GABAergic Neurotransmission in IMR-32 Cells.","authors":"Filatova, Elena; Kasian, Anastasiya; Kolomin, Timur; Rybalkina, Ekaterina; Alieva, Anelya; Andreeva, Lyudmila; Limborska, Svetlana; Myasoedov, Nikolay; Pavlova, Galina; Slominsky, Petr; Shadrina, Maria","year":2017,"journal":"Frontiers in pharmacology, 8, 89","doi":"10.3389/fphar.2017.00089","pmid":"28293190","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03287","title":"Stapled Voltage-Gated Calcium Channel (CaV) α-Interaction Domain (AID) Peptides Act As Selective Protein-Protein Interaction Inhibitors of CaV Function.","authors":"Findeisen, Felix; Campiglio, Marta; Jo, Hyunil; Abderemane-Ali, Fayal; Rumpf, Christine H; Pope, Lianne; Rossen, Nathan D; Flucher, Bernhard E; DeGrado, William F; Minor, Daniel L","year":2017,"journal":"ACS chemical neuroscience, 8(6), 1313-1326","doi":"10.1021/acschemneuro.6b00454","pmid":"28278376","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Meta-xylyl stapled peptides targeting the CaV α-interaction domain (AID) were developed and characterized:\n\n- Structural: Staples enhanced helical structure (CD spectroscopy) and maintained native-like AID:CaVβ binding geometry (X-ray crystallography)\n- Thermodynamic: Stapling reduced the entropic penalty of binding (ITC), improving affinity\n- Functional: Stapled AID peptides effectively inhibited the CaVα1:CaVβ protein-protein interaction\n- Selectivity: Modulation was CaVβ isoform-selective, demonstrating that different beta subunits can be preferentially targeted\n\nThis represents the first proof-of-concept for using protein-protein interaction inhibitors to control voltage-gated ion channel function.","whyItMatters":"Voltage-gated calcium channels are drug targets for heart disease (arrhythmias, hypertension), pain, epilepsy, and more. Current calcium channel blockers (like amlodipine, verapamil) block the channel pore non-selectively. Targeting the protein-protein interactions that assemble the channel offers a completely new approach: you could selectively disable specific channel subtypes in specific tissues. Stapled peptides provide the structural rigidity needed to effectively disrupt these large protein interfaces, which small molecule drugs struggle to do.","specificNumbers":"","methodology":"Stapled peptides were designed based on the AID helix that mediates CaVα-CaVβ interaction. Meta-xylyl chemical staples were incorporated to stabilize helical structure. Structural characterization used circular dichroism spectroscopy and X-ray crystallography. Binding thermodynamics were measured by isothermal titration calorimetry. Functional effects on calcium channel activity were assessed by electrophysiological recordings, testing selectivity across CaVβ isoforms.","limitations":"This is a proof-of-concept study demonstrating feasibility, not a drug development study. The peptides were tested in controlled in vitro and cellular electrophysiology systems that don't recapitulate in vivo pharmacology. Cell permeability, metabolic stability, and in vivo efficacy of the stapled peptides were not assessed. The selectivity between CaVβ isoforms, while demonstrated, may not be sufficient for therapeutic selectivity between tissues. Translation from stapled peptides to practical therapeutics faces significant drug delivery challenges."},{"rthcId":"RPEP-03288","title":"TRPA1, substance P, histamine and 5-hydroxytryptamine interact in an interdependent way to induce nociception.","authors":"Fischer, Luana; Lavoranti, Maria Isabel; de Oliveira Borges, Mariana; Miksza, Alana Farias; Sardi, Natalia Fantin; Martynhak, Bruno Jacson; Tambeli, Claudia H; Parada, Carlos Amílcar","year":2017,"journal":"Inflammation research : official journal of the European Histamine Research Society ... [et al.], 66(4), 311-322","doi":"10.1007/s00011-016-1015-1","pmid":"27904941","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03289","title":"The effects of substance P and acetylcholine on human tenocyte proliferation converge mechanistically via TGF-β1.","authors":"Fong, Gloria; Backman, Ludvig J; Alfredson, Håkan; Scott, Alex; Danielson, Patrik","year":2017,"journal":"PloS one, 12(3), e0174101","doi":"10.1371/journal.pone.0174101","pmid":"28301610","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03290","title":"Kisspeptin Stimulates Growth Hormone Release by Utilizing Neuropeptide Y Pathways and Is Dependent on the Presence of Ghrelin in the Ewe.","authors":"Foradori, Chad D; Whitlock, Brian K; Daniel, Jay A; Zimmerman, Arthur D; Jones, Melaney A; Read, Casey C; Steele, Barbara P; Smith, Jeremy T; Clarke, Iain J; Elsasser, Theodore H; Keisler, Duane H; Sartin, James L","year":2017,"journal":"Endocrinology, 158(10), 3526-3539","doi":"10.1210/en.2017-00303","pmid":"28977590","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Central kisspeptin delivery caused robust growth hormone (GH) release in fasted sheep but not in fed sheep. The proposed mechanism involves a cascade of peptide interactions:\n\n1. During fasting, systemic ghrelin rises and NPY expression in the arcuate nucleus increases\n2. Kisspeptin activates NPY neurons (confirmed by c-Fos activation)\n3. NPY stimulates GHRH neurons and inhibits somatostatin neurons\n4. This results in GH release\n\nCritical evidence:\n- NPY Y1 receptor antagonist (BIBO 3304) blocked kisspeptin-induced GH release\n- Kisspeptin induced c-Fos in NPY and GHRH cells of the arcuate nucleus\n- Kisspeptin reduced c-Fos in somatostatin cells\n- Blocking ghrelin (systemically or at its receptor) eliminated or reduced kisspeptin-induced GH release\n- Effects were similar at 24h and 72h fasting, indicating response to food loss rather than severe energy deficit","whyItMatters":"This study reveals a previously unknown connection between kisspeptin (a reproductive peptide), NPY (an appetite peptide), ghrelin (a hunger peptide), and growth hormone. This interconnection explains how the body coordinates reproductive function with nutritional and growth status — a fundamental biological question. It also has practical implications for peptide therapy, suggesting that the effects of kisspeptin or ghrelin-based treatments may vary significantly with feeding state.","specificNumbers":"","methodology":"Researchers used central (intracerebroventricular) kisspeptin delivery in female sheep under fed and fasted conditions (24h and 72h). Blood samples measured GH levels. NPY Y1 receptor antagonist pretreatment tested NPY involvement. Ghrelin blockade (systemic and receptor-level) tested ghrelin dependence. Immunohistochemistry for c-Fos identified which hypothalamic neuron populations were activated by kisspeptin.","limitations":"This study was conducted in sheep, which share many neuroendocrine features with humans but are not identical. The central delivery route (intracerebroventricular) does not mimic normal kisspeptin signaling, which occurs locally within the hypothalamus. The study used only female sheep, and sex differences in these pathways are likely significant. The exact mechanism by which ghrelin enables kisspeptin-induced GH release requires further elucidation."},{"rthcId":"RPEP-03291","title":"Autoantigens ADAMTSL5 and LL37 are significantly upregulated in active Psoriasis and localized with keratinocytes, dendritic cells and other leukocytes.","authors":"Fuentes-Duculan, Judilyn; Bonifacio, Kathleen M; Hawkes, Jason E; Kunjravia, Norma; Cueto, Inna; Li, Xuan; Gonzalez, Juana; Garcet, Sandra; Krueger, James G","year":2017,"journal":"Experimental dermatology, 26(11), 1075-1082","doi":"10.1111/exd.13378","pmid":"28482118","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03292","title":"Contractile properties of periosteal arterioles in the guinea-pig tibia.","authors":"Fukuta, Hiroyasu; Mitsui, Retsu; Takano, Hiromichi; Hashitani, Hikaru","year":2017,"journal":"Pflugers Archiv : European journal of physiology, 469(9), 1203-1213","doi":"10.1007/s00424-017-1980-4","pmid":"28466243","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03293","title":"A Short Double-Stapled Peptide Inhibits Respiratory Syncytial Virus Entry and Spreading.","authors":"Gaillard, Vanessa; Galloux, Marie; Garcin, Dominique; Eléouët, Jean-François; Le Goffic, Ronan; Larcher, Thibaut; Rameix-Welti, Marie-Anne; Boukadiri, Abdelhak; Héritier, Julien; Segura, Jean-Manuel; Baechler, Elodie; Arrell, Miriam; Mottet-Osman, Geneviève; Nyanguile, Origène","year":2017,"journal":"Antimicrobial agents and chemotherapy, 61(4)","doi":"10.1128/AAC.02241-16","pmid":"28137809","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03294","title":"Bicuculline, a GABAA-receptor antagonist, blocked HPA axis activation induced by ghrelin under an acute stress.","authors":"Gastón, M S; Cid, M P; Salvatierra, N A","year":2017,"journal":"Behavioural brain research, 320, 464-472","doi":"10.1016/j.bbr.2016.10.035","pmid":"27780724","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03295","title":"Growth hormone-releasing hormone attenuates cardiac hypertrophy and improves heart function in pressure overload-induced heart failure.","authors":"Gesmundo, Iacopo; Miragoli, Michele; Carullo, Pierluigi; Trovato, Letizia; Larcher, Veronica; Di Pasquale, Elisa; Brancaccio, Mara; Mazzola, Marta; Villanova, Tania; Sorge, Matteo; Taliano, Marina; Gallo, Maria Pia; Alloatti, Giuseppe; Penna, Claudia; Hare, Joshua M; Ghigo, Ezio; Schally, Andrew V; Condorelli, Gianluigi; Granata, Riccarda","year":2017,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 114(45), 12033-12038","doi":"10.1073/pnas.1712612114","pmid":"29078377","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GHRH and its agonistic analog MR-409 attenuated cardiac hypertrophy both in vitro and in vivo. In cell models (H9c2 cardiac cells, adult rat ventricular myocytes, and human iPSC-derived cardiomyocytes), GHRH reduced phenylephrine-induced hypertrophy by blocking Gq signaling and its downstream components (phospholipase Cβ, PKCε, calcineurin, phospholamban) while activating Gαs/cAMP/PKA and inhibiting Epac1. In vivo, MR-409 mitigated cardiac hypertrophy in mice with pressure overload from transverse aortic constriction, improved cardiac function, and restored cardiomyocyte contractility and sarcolemmal structure.","whyItMatters":"Heart failure caused by pathological cardiac hypertrophy is a leading cause of death worldwide with limited therapeutic options. This study, published in PNAS, identifies GHRH as a previously unknown anti-hypertrophic regulator of the heart and demonstrates that GHRH analogs could be repurposed as treatments for heart failure — a potential new application for a well-characterized peptide hormone class.","specificNumbers":"","methodology":"Multi-level approach: in vitro hypertrophy was induced with phenylephrine in three cell types (H9c2 cardiac cells, adult rat ventricular myocytes, and human iPSC-derived cardiomyocytes) and treated with GHRH(1-44)NH2. Hypertrophic gene expression and signaling pathways were measured. In vivo, mice underwent transverse aortic constriction (TAC) to create pressure overload, then received the GHRH agonist MR-409. Cardiac function, hypertrophy markers, cardiomyocyte contractility, and sarcolemmal structure were assessed.","limitations":"While the study uses human iPSC-derived cardiomyocytes in vitro, the in vivo work is limited to mice. The TAC model creates acute pressure overload which may not fully replicate the gradual development of heart failure in humans. Long-term safety of GHRH agonists in cardiac patients — including effects on growth hormone levels and potential tumor promotion — is not addressed. The study does not compare MR-409 to existing heart failure treatments."},{"rthcId":"RPEP-03296","title":"The Role of Episodic Postprandial Peptides in Exercise-Induced Compensatory Eating.","authors":"Gibbons, Catherine; Blundell, John E; Caudwell, Phillipa; Webb, Dominic-Luc; Hellström, Per M; Näslund, Erik; Finlayson, Graham","year":2017,"journal":"The Journal of clinical endocrinology and metabolism, 102(11), 4051-4059","doi":"10.1210/jc.2017-00817","pmid":"28938473","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03297","title":"Effects of randomized whey-protein loads on energy intake, appetite, gastric emptying, and plasma gut-hormone concentrations in older men and women.","authors":"Giezenaar, Caroline; Trahair, Laurence G; Luscombe-Marsh, Natalie D; Hausken, Trygve; Standfield, Scott; Jones, Karen L; Lange, Kylie; Horowitz, Michael; Chapman, Ian; Soenen, Stijn","year":2017,"journal":"The American journal of clinical nutrition, 106(3), 865-877","doi":"10.3945/ajcn.117.154377","pmid":"28747330","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03298","title":"Investigation of phosphorylated adjuvants co-encapsulated with a model cancer peptide antigen for the treatment of colorectal cancer and liver metastasis.","authors":"Goodwin, Tyler J; Huang, Leaf","year":2017,"journal":"Vaccine, 35(19), 2550-2557","doi":"10.1016/j.vaccine.2017.03.067","pmid":"28385609","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03299","title":"Anamorelin hydrochloride in the treatment of cancer anorexia-cachexia syndrome: design, development, and potential place in therapy.","authors":"Graf, Solomon A; Garcia, Jose M","year":2017,"journal":"Drug design, development and therapy, 11, 2325-2331","doi":"10.2147/DDDT.S110131","pmid":"28848326","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03300","title":"Double quick, double click reversible peptide \"stapling\".","authors":"Grison, Claire M; Burslem, George M; Miles, Jennifer A; Pilsl, Ludwig K A; Yeo, David J; Imani, Zeynab; Warriner, Stuart L; Webb, Michael E; Wilson, Andrew J","year":2017,"journal":"Chemical science, 8(7), 5166-5171","doi":"10.1039/c7sc01342f","pmid":"28970902","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03301","title":"Optimization of an Enzymatic Antibody-Drug Conjugation Approach Based on Coenzyme A Analogs.","authors":"Grünewald, Jan; Jin, Yunho; Vance, Julie; Read, Jessica; Wang, Xing; Wan, Yongqin; Zhou, Huanfang; Ou, Weijia; Klock, Heath E; Peters, Eric C; Uno, Tetsuo; Brock, Ansgar; Geierstanger, Bernhard H","year":2017,"journal":"Bioconjugate chemistry, 28(7), 1906-1915","doi":"10.1021/acs.bioconjchem.7b00236","pmid":"28590752","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03302","title":"AgRP-Expressing Adrenal Chromaffin Cells Are Involved in the Sympathetic Response to Fasting.","authors":"Gupta, Rajesh; Ma, Yunbing; Wang, Manqi; Whim, Matthew D","year":2017,"journal":"Endocrinology, 158(8), 2572-2584","doi":"10.1210/en.2016-1268","pmid":"28531318","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03303","title":"Preprotachykinin A is expressed by a distinct population of excitatory neurons in the mouse superficial spinal dorsal horn including cells that respond to noxious and pruritic stimuli.","authors":"Gutierrez-Mecinas, Maria; Bell, Andrew M; Marin, Alina; Taylor, Rebecca; Boyle, Kieran A; Furuta, Takahiro; Watanabe, Masahiko; Polgár, Erika; Todd, Andrew J","year":2017,"journal":"Pain, 158(3), 440-456","doi":"10.1097/j.pain.0000000000000778","pmid":"27902570","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03304","title":"Risks of unregulated use of alpha-melanocyte-stimulating hormone analogues: a review.","authors":"Habbema, Louis; Halk, Anne Berthe; Neumann, Martino; Bergman, Wilma","year":2017,"journal":"International journal of dermatology, 56(10), 975-980","doi":"10.1111/ijd.13585","pmid":"28266027","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03305","title":"Synthetic peptides designed to modulate adiponectin assembly improve obesity-related metabolic disorders.","authors":"Hampe, Lutz; Xu, Cheng; Harris, Paul W R; Chen, Jie; Liu, Ming; Middleditch, Martin; Radjainia, Mazdak; Wang, Yu; Mitra, Alok K","year":2017,"journal":"British journal of pharmacology, 174(23), 4478-4492","doi":"10.1111/bph.14050","pmid":"28945274","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03306","title":"Dynamic and specific immune responses against multiple tumor antigens were elicited in patients with hepatocellular carcinoma after cell-based immunotherapy.","authors":"Han, Yanyan; Wu, Yeting; Yang, Chou; Huang, Jing; Guo, Yabing; Liu, Li; Chen, Ping; Wu, Dongyun; Liu, Junyun; Li, Jin; Zhou, Xiangjun; Hou, Jinlin","year":2017,"journal":"Journal of translational medicine, 15(1), 64","doi":"10.1186/s12967-017-1165-0","pmid":"28330473","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03307","title":"Targeting kinase signaling pathways with constrained peptide scaffolds.","authors":"Hanold, Laura E; Fulton, Melody D; Kennedy, Eileen J","year":2017,"journal":"Pharmacology & therapeutics, 173, 159-170","doi":"10.1016/j.pharmthera.2017.02.014","pmid":"28185915","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03308","title":"Killing of Staphylococcus aureus and Salmonella enteritidis and neutralization of lipopolysaccharide by 17-residue bovine lactoferricins: improved activity of Trp/Ala-containing molecules.","authors":"Hao, Ya; Yang, Na; Wang, Xiumin; Teng, Da; Mao, Ruoyu; Wang, Xiao; Li, Zhanzhan; Wang, Jianhua","year":2017,"journal":"Scientific reports, 7, 44278","doi":"10.1038/srep44278","pmid":"28287172","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03309","title":"Oxytocin attenuates deficits in social interaction but not recognition memory in a prenatal valproic acid-induced mouse model of autism.","authors":"Hara, Yuta; Ago, Yukio; Higuchi, Momoko; Hasebe, Shigeru; Nakazawa, Takanobu; Hashimoto, Hitoshi; Matsuda, Toshio; Takuma, Kazuhiro","year":2017,"journal":"Hormones and behavior, 96, 130-136","doi":"10.1016/j.yhbeh.2017.09.013","pmid":"28942000","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A single intranasal dose of oxytocin restored social interaction deficits for up to 2 hours in VPA-exposed mice. A 2-week course of daily intranasal oxytocin extended this improvement to at least 24 hours after the last dose. Neither single nor repeated administration improved recognition memory impairments.\n\nImmunohistochemical analysis revealed that oxytocin increased c-Fos expression (a marker of neuronal activation) in the paraventricular nuclei (PVN), prefrontal cortex, and somatosensory cortex of VPA-exposed mice, but not in hippocampal CA1 or CA3 regions. This selective activation pattern explains the differential effects — social circuits were engaged while memory circuits were not. Importantly, oxytocin had no effect on social behavior in control mice, suggesting it specifically corrects the deficit rather than broadly enhancing sociality.","whyItMatters":"Understanding exactly what oxytocin can and cannot improve in autism is critical for setting realistic therapeutic expectations. This study shows that oxytocin selectively improves social interaction — a core deficit in autism — through activation of specific brain circuits, but it is not a blanket cognitive enhancer. The finding that repeated dosing extends benefits beyond the acute period is encouraging for potential clinical use, and the brain activation data provides mechanistic insight into how oxytocin works.","specificNumbers":"","methodology":"Researchers used ICR mice prenatally exposed to valproic acid (VPA) as an autism spectrum disorder model. Oxytocin was administered intranasally — either as a single dose or daily for 2 weeks. Social interaction was assessed using standard behavioral tests, and recognition memory was evaluated separately. Brain activation was mapped using c-Fos immunohistochemistry to identify which brain regions responded to oxytocin treatment. Control mice received the same treatments for comparison.","limitations":"This is a mouse study using a single autism model (prenatal VPA exposure), which does not capture the full genetic and phenotypic diversity of human autism spectrum disorder. The specific doses of oxytocin used were not detailed in the abstract. Brain activation was measured by c-Fos expression, which is an indirect marker of neuronal activity. The duration of the repeated dosing study was only 2 weeks, and longer-term effects are unknown. Translation from intranasal delivery in mice to humans faces challenges in dosing and brain penetration."},{"rthcId":"RPEP-03310","title":"Direct versus indirect actions of ghrelin on hypothalamic NPY neurons.","authors":"Hashiguchi, Hiroshi; Sheng, Zhenyu; Routh, Vanessa; Gerzanich, Volodymyr; Simard, J Marc; Bryan, Joseph","year":2017,"journal":"PloS one, 12(9), e0184261","doi":"10.1371/journal.pone.0184261","pmid":"28877214","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03311","title":"Effect of Semaglutide on the Pharmacokinetics of Metformin, Warfarin, Atorvastatin and Digoxin in Healthy Subjects.","authors":"Hausner, Helene; Derving Karsbøl, Julie; Holst, Anders G; Jacobsen, Jacob B; Wagner, Frank-Dietrich; Golor, Georg; Anderson, Thomas W","year":2017,"journal":"Clinical pharmacokinetics, 56(11), 1391-1401","doi":"10.1007/s40262-017-0532-6","pmid":"28349387","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03312","title":"Designer bFGF-incorporated d-form self-assembly peptide nanofiber scaffolds to promote bone repair.","authors":"He, Bin; Ou, Yunsheng; Chen, Shuo; Zhao, Weikang; Zhou, Ao; Zhao, Jinqiu; Li, Hong; Jiang, Dianming; Zhu, Yong","year":2017,"journal":"Materials science & engineering. C, Materials for biological applications, 74, 451-458","doi":"10.1016/j.msec.2016.12.042","pmid":"28254316","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03313","title":"Cutaneous neurogenic inflammation in the sensitized acupoints induced by gastric mucosal injury in rats.","authors":"He, Wei; Wang, Xiao-Yu; Shi, Hong; Bai, Wan-Zhu; Cheng, Bin; Su, Yang-Shuai; Yu, Xiao-Chun; Jing, Xiang-Hong; Zhu, Bing","year":2017,"journal":"BMC complementary and alternative medicine, 17(1), 141","doi":"10.1186/s12906-017-1580-z","pmid":"28270193","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03314","title":"Comparison of the Level of Substance P and Neurokinin A in Gingival Crevicular Fluid of Sound and Symptomatic Carious Primary Teeth by ELISA.","authors":"Heidari, Alireza; Shahrabi, Mehdi; Shahrabi, Marzieh Salehi; Ghandehari, Mehdi; Rahbar, Pegah","year":2017,"journal":"Journal of dentistry (Tehran, Iran), 14(4), 173-179","doi":null,"pmid":"29285027","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03315","title":"Optimization of process parameters for the production of collagen peptides from fish skin (Epinephelus malabaricus) using response surface methodology and its characterization.","authors":"Hema, G S; Joshy, C G; Shyni, K; Chatterjee, Niladri S; Ninan, George; Mathew, Suseela","year":2017,"journal":"Journal of food science and technology, 54(2), 488-496","doi":"10.1007/s13197-017-2490-2","pmid":"28242948","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03316","title":"Cardiovascular Outcome Trial Update in Diabetes: New Evidence, Remaining Questions.","authors":"Herbst, Rebecca; Bolton, Wilburn; Shariff, Afreen; Green, Jennifer B","year":2017,"journal":"Current diabetes reports, 17(9), 67","doi":"10.1007/s11892-017-0898-8","pmid":"28726152","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03317","title":"Impact of Psychological Stress on Pain Perception in an Animal Model of Endometriosis.","authors":"Hernandez, Siomara; Cruz, Myrella L; Seguinot, Inevy I; Torres-Reveron, Annelyn; Appleyard, Caroline B","year":2017,"journal":"Reproductive sciences (Thousand Oaks, Calif.), 24(10), 1371-1381","doi":"10.1177/1933719116687655","pmid":"28093054","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03318","title":"Oral supplementation with specific bioactive collagen peptides improves nail growth and reduces symptoms of brittle nails.","authors":"Hexsel, Doris; Zague, Vivian; Schunck, Michael; Siega, Carolina; Camozzato, Fernanda O; Oesser, Steffen","year":2017,"journal":"Journal of cosmetic dermatology, 16(4), 520-526","doi":"10.1111/jocd.12393","pmid":"28786550","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03319","title":"Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes.","authors":"Holman, Rury R; Bethel, M Angelyn; Mentz, Robert J; Thompson, Vivian P; Lokhnygina, Yuliya; Buse, John B; Chan, Juliana C; Choi, Jasmine; Gustavson, Stephanie M; Iqbal, Nayyar; Maggioni, Aldo P; Marso, Steven P; Öhman, Peter; Pagidipati, Neha J; Poulter, Neil; Ramachandran, Ambady; Zinman, Bernard; Hernandez, Adrian F","year":2017,"journal":"The New England journal of medicine, 377(13), 1228-1239","doi":"10.1056/NEJMoa1612917","pmid":"28910237","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03320","title":"An Amphibian Host Defense Peptide Is Virucidal for Human H1 Hemagglutinin-Bearing Influenza Viruses.","authors":"Holthausen, David J; Lee, Song Hee; Kumar, Vineeth Tv; Bouvier, Nicole M; Krammer, Florian; Ellebedy, Ali H; Wrammert, Jens; Lowen, Anice C; George, Sanil; Pillai, Madhavan Radhakrishna; Jacob, Joshy","year":2017,"journal":"Immunity, 46(4), 587-595","doi":"10.1016/j.immuni.2017.03.018","pmid":"28423338","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03321","title":"From Belly to Brain: Targeting the Ghrelin Receptor in Appetite and Food Intake Regulation.","authors":"Howick, Ken; Griffin, Brendan T; Cryan, John F; Schellekens, Harriët","year":2017,"journal":"International journal of molecular sciences, 18(2)","doi":"10.3390/ijms18020273","pmid":"28134808","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Ghrelin's central brain signaling is critical for its effects on appetite, body weight, and food reward. However, multiple factors have prevented successful drug development: GHSR-1a receptor internalization and heterodimerization create complex pharmacology, biased ligand interactions produce unpredictable effects, compensatory neuroendocrine outputs counteract drug effects, and the receptor's ubiquitous expression makes it impossible to target appetite without affecting peripheral ghrelin functions. Improving blood-brain barrier penetration of ghrelin ligands, particularly to reach mesolimbic reward circuitry, is identified as a key priority.","whyItMatters":"Understanding why ghrelin-targeting drugs haven't succeeded explains a major gap in the obesity and cachexia treatment landscape. While GLP-1 drugs have conquered the satiety side of appetite, the hunger side — driven by ghrelin — remains pharmacologically intractable. Solving the ghrelin drug delivery and receptor selectivity challenges could complement existing GLP-1 therapies and address conditions where appetite stimulation is needed, such as cancer cachexia and anorexia in the elderly.","specificNumbers":"","methodology":"Narrative review of the ghrelin system biology, receptor pharmacology, and therapeutic development efforts for appetite modulation, covering both preclinical and clinical evidence.","limitations":"As a 2017 review, it predates some recent advances in ghrelin pharmacology and drug delivery. The review covers a wide scope, which limits depth on individual drug candidates. The emphasis on challenges may understate progress in understanding ghrelin biology. Some therapeutic leads mentioned may have since advanced or been abandoned."},{"rthcId":"RPEP-03322","title":"Therapeutic potential of pro-angiogenic BPC157 is associated with VEGFR2 activation and up-regulation.","authors":"Hsieh, Ming-Jer; Liu, Hsien-Ta; Wang, Chao-Nin; Huang, Hsiu-Yun; Lin, Yuling; Ko, Yu-Shien; Wang, Jong-Shyan; Chang, Vincent Hung-Shu; Pang, Jong-Hwei S","year":2017,"journal":"Journal of molecular medicine (Berlin, Germany), 95(3), 323-333","doi":"10.1007/s00109-016-1488-y","pmid":"27847966","tags":[],"studyType":"Animal/In Vitro Study","evidenceStrength":"preliminary","keyFinding":"BPC-157 promotes the growth of new blood vessels (angiogenesis) through a specific molecular mechanism: it increases the expression and internalization of VEGFR2, a key receptor for blood vessel growth, and activates the downstream VEGFR2-Akt-eNOS signaling pathway.\n\nThe study demonstrated this across multiple experimental models. In a chick embryo membrane assay, BPC-157 increased vessel density. In human endothelial cell cultures, it enhanced tube formation (a measure of blood vessel growth). Most notably, in rats with restricted blood flow to a hind limb (ischemia model), BPC-157 accelerated blood flow recovery and increased the number of blood vessels, with enhanced VEGFR2 expression confirmed by tissue analysis.\n\nImportantly, BPC-157 upregulated the VEGFR2 receptor itself but not the VEGF-A ligand — meaning it works by making cells more responsive to existing growth signals rather than producing more growth factor. Blocking endocytosis with dynasore inhibited BPC-157's effects, confirming that receptor internalization is a required step in the mechanism.","whyItMatters":"BPC-157 has been widely studied for its healing properties, but the molecular mechanism behind how it promotes tissue repair has been poorly understood. This study provides one of the clearest mechanistic explanations to date — showing that BPC-157 works by upregulating and activating the VEGFR2 pathway, which is the same pathway targeted by anti-cancer drugs (in reverse). Understanding this mechanism is crucial for evaluating both the therapeutic potential and safety implications of BPC-157.","specificNumbers":"Increased vessel density in CAM assay · Enhanced tube formation in vitro · Accelerated blood flow recovery in rat ischemia model · VEGFR2 upregulation confirmed at mRNA and protein level · VEGFR2-Akt-eNOS pathway activation","methodology":"Multi-model preclinical study combining: (1) chick chorioallantoic membrane (CAM) assay for in vivo angiogenesis, (2) human umbilical vein endothelial cell (HUVEC) tube formation assays in vitro, (3) rat hind limb ischemia model with laser Doppler blood flow scanning, and (4) molecular analysis of VEGFR2 expression, internalization, and downstream signaling. Dynasore (an endocytosis inhibitor) was used to confirm the mechanism.","limitations":"Animal and cell culture study only — no human data. The rat ischemia model, while informative, doesn't directly translate to human healing scenarios. Specific doses and concentrations used in each model aren't detailed in the abstract. The long-term effects and safety of VEGFR2 upregulation by BPC-157 are not addressed, which is relevant given that excessive angiogenesis can promote tumor growth."},{"rthcId":"RPEP-03323","title":"The lactoferricin B-derived peptide, LfB17-34, induces melanogenesis in B16F10 cells.","authors":"Huang, Hsiu-Chin; Lin, Hsuan; Huang, Min-Chuan","year":2017,"journal":"International journal of molecular medicine, 39(3), 595-602","doi":"10.3892/ijmm.2017.2884","pmid":"28204812","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03324","title":"Ghrelin alleviates anxiety- and depression-like behaviors induced by chronic unpredictable mild stress in rodents.","authors":"Huang, Hui-Jie; Zhu, Xiao-Cang; Han, Qiu-Qin; Wang, Ya-Lin; Yue, Na; Wang, Jing; Yu, Rui; Li, Bing; Wu, Gen-Cheng; Liu, Qiong; Yu, Jin","year":2017,"journal":"Behavioural brain research, 326, 33-43","doi":"10.1016/j.bbr.2017.02.040","pmid":"28245976","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03325","title":"The Growth Hormone Secretagogue Hexarelin Protects Rat Cardiomyocytes From in vivo Ischemia/Reperfusion Injury Through Interleukin-1 Signaling Pathway.","authors":"Huang, Jiannan; Li, Yi; Zhang, Juan; Liu, Yusheng; Lu, Qinghua","year":2017,"journal":"International heart journal, 58(2), 257-263","doi":"10.1536/ihj.16-241","pmid":"28321024","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03326","title":"Synthetic Peptides Derived from Bovine Lactoferricin Exhibit Antimicrobial Activity against E. coli ATCC 11775, S. maltophilia ATCC 13636 and S. enteritidis ATCC 13076.","authors":"Huertas Méndez, Nataly De Jesús; Vargas Casanova, Yerly; Gómez Chimbi, Anyelith Katherine; Hernández, Edith; Leal Castro, Aura Lucia; Melo Diaz, Javier Mauricio; Rivera Monroy, Zuly Jenny; García Castañeda, Javier Eduardo","year":2017,"journal":"Molecules (Basel, Switzerland), 22(3)","doi":"10.3390/molecules22030452","pmid":"28287494","tags":[],"studyType":"in-vitro","evidenceStrength":"low-moderate","keyFinding":"Researchers synthesized multiple peptide variants derived from bovine lactoferricin — a natural antimicrobial peptide found in cow's milk — and tested their antibacterial activity. The dimeric peptide (RRWQWR)₂K-Ahx showed the strongest overall activity against the tested bacteria. Monomeric, cyclic, tetrameric, and palindromic peptides containing the RWQWR motif all showed high and specific activity against E. coli.\n\nDifferent peptide architectures (linear, dimeric, tetrameric, cyclic) produced different activity profiles, demonstrating that how you arrange the same antimicrobial sequence significantly affects which bacteria it kills. The peptides were effective against both E. coli and Salmonella enteritidis but showed varying activity against Stenotrophomonas maltophilia.","whyItMatters":"Lactoferricin is one of nature's most potent antimicrobial peptides, found in the milk that protects newborn calves from infection. By breaking it down to its essential antimicrobial sequence (the RWQWR motif) and testing different structural arrangements, this study maps out how to engineer optimized synthetic versions. With antibiotic resistance rising, milk-derived antimicrobial peptides offer a natural starting point for new antibiotics, and understanding structure-activity relationships is key to making them practical drugs.","specificNumbers":"3 bacterial strains tested (E. coli, S. maltophilia, S. enteritidis) · 4 peptide architectures (linear, dimeric, tetrameric, cyclic) · RWQWR core motif · (RRWQWR)₂K-Ahx = highest activity · MIC and MBC determined for each combination","methodology":"Peptide variants were synthesized using solid-phase peptide synthesis, then purified and characterized using RP-HPLC, MALDI-TOF mass spectrometry, and circular dichroism spectroscopy. Antibacterial activity was tested against three reference bacterial strains by determining minimum inhibitory concentration (MIC — lowest concentration that stops growth) and minimum bactericidal concentration (MBC — lowest concentration that kills bacteria).","limitations":"This is an in vitro study using reference laboratory bacterial strains (ATCC), which may not represent the drug-resistant clinical isolates that are the biggest problem in hospitals. No toxicity testing against human cells was reported, which is critical since antimicrobial peptides can be toxic to mammalian cells. No animal or human studies were conducted. The RWQWR motif variants haven't been tested for stability in biological fluids."},{"rthcId":"RPEP-03327","title":"Antimicrobial Activity of Truncated and Polyvalent Peptides Derived from the FKCRRQWQWRMKKGLA Sequence against Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 25923.","authors":"Huertas, Nataly de Jesús; Monroy, Zuly Jenny Rivera; Medina, Ricardo Fierro; Castañeda, Javier Eduardo García","year":2017,"journal":"Molecules (Basel, Switzerland), 22(6)","doi":"10.3390/molecules22060987","pmid":"28613262","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03328","title":"Evaluation of NT-proBNP in children with heart failure younger than 3 years old.","authors":"Iacob, Daniela; Butnariu, Angela; Leucuţa, Daniel-Corneliu; Samaşca, Gabriel; Deleanu, Diana; Lupan, Iulia","year":2017,"journal":"Romanian journal of internal medicine = Revue roumaine de medecine interne, 55(2), 69-74","doi":"10.1515/rjim-2017-0002","pmid":"28118147","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03329","title":"Analgesia by Deletion of Spinal Neurokinin 1 Receptor Expressing Neurons Using a Bioengineered Substance P-Pseudomonas Exotoxin Conjugate.","authors":"Iadarola, Michael J; Sapio, Matthew R; Wang, Xunde; Carrero, Hector; Virata-Theimer, Maria Luisa; Sarnovsky, Robert; Mannes, Andrew J; FitzGerald, David J","year":2017,"journal":"Molecular pain, 13, 1744806917727657","doi":"10.1177/1744806917727657","pmid":"28814145","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03330","title":"Novel angiotensin-converting enzyme inhibitory peptides from caseins and whey proteins of goat milk.","authors":"Ibrahim, Hisham R; Ahmed, Ahmed S; Miyata, Takeshi","year":2017,"journal":"Journal of advanced research, 8(1), 63-71","doi":"10.1016/j.jare.2016.12.002","pmid":"28053783","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03331","title":"Novel strategies in the oral delivery of antidiabetic peptide drugs - Insulin, GLP 1 and its analogs.","authors":"Ismail, Ruba; Csóka, Ildikó","year":2017,"journal":"European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 115, 257-267","doi":"10.1016/j.ejpb.2017.03.015","pmid":"28336368","tags":["peptide-drug-delivery","diabetes","glp-1-agonists"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"The review evaluated multiple strategies for oral delivery of antidiabetic peptides (insulin, GLP-1, and GLP-1 analogs), identifying two main barriers that must be overcome: degradation by proteolytic enzymes in the gastrointestinal tract and poor absorption through the intestinal wall.\n\nAmong all approaches reviewed — including absorption enhancers, enzyme inhibitors, chemical modifications, and various carrier systems — nanocarrier systems emerged as the most promising platform. These include polymeric nanoparticles, solid lipid nanoparticles, liposomes, and micelles, each with distinct advantages for protecting peptides from degradation and enhancing their absorption. However, the authors noted that no FDA-approved oral antidiabetic peptide delivery system existed at the time of publication, and further development was needed.","whyItMatters":"Diabetes affects over 500 million people worldwide, and many require injectable peptide drugs. The inconvenience, pain, and needle phobia associated with injections reduce adherence and delay treatment initiation. Converting these drugs to oral pills would be transformative for patient quality of life and could improve diabetes outcomes on a population level. This review captures the state of the field just before oral semaglutide (Rybelsus) became the first oral GLP-1 drug to reach the market.","specificNumbers":"Strategies reviewed: nanoparticles, solid lipid NPs, liposomes, micelles · Targets: insulin, GLP-1, GLP-1 analogs · Key barriers: enzymatic degradation + poor GI absorption","methodology":"This was a narrative review that surveyed the published scientific literature on strategies for oral delivery of antidiabetic peptide drugs. The authors evaluated the advantages and limitations of each approach, including nanocarrier systems, absorption enhancers, enzyme inhibitors, mucoadhesive systems, and chemical modification strategies, with a focus on insulin, GLP-1, and GLP-1 analogs.","limitations":"This review predates the approval of oral semaglutide (Rybelsus, 2019), which used an absorption enhancer approach rather than nanocarriers. The nanocarrier strategies highlighted as most promising have not yet produced FDA-approved products. As a narrative review, it does not systematically assess study quality. The field has advanced significantly since 2017."},{"rthcId":"RPEP-03332","title":"A novel GLP-1/GIP dual receptor agonist protects from 6-OHDA lesion in a rat model of Parkinson's disease.","authors":"Jalewa, Jaishree; Sharma, Mohit Kumar; Gengler, Simon; Hölscher, Christian","year":2017,"journal":"Neuropharmacology, 117, 238-248","doi":"10.1016/j.neuropharm.2017.02.013","pmid":"28223210","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03333","title":"A short history of phototherapy, vitamin D and skin disease.","authors":"Jarrett, Paul; Scragg, Robert","year":2017,"journal":"Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology, 16(3), 283-290","doi":"10.1039/c6pp00406g","pmid":"27892584","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03334","title":"Antimicrobial peptide LL-37 promotes YB-1 expression, and the viability, migration and invasion of malignant melanoma cells.","authors":"Jia, Jinjing; Zheng, Yan; Wang, Wei; Shao, Yongping; Li, Zhengxiao; Wang, Qiong; Wang, Yuan; Yan, Huling","year":2017,"journal":"Molecular medicine reports, 15(1), 240-248","doi":"10.3892/mmr.2016.5978","pmid":"27922666","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03335","title":"Nanoparticle fullerol alleviates radiculopathy via NLRP3 inflammasome and neuropeptides.","authors":"Jin, Li; Ding, Mengmeng; Oklopcic, Azra; Aghdasi, Bayan; Xiao, Li; Li, Ziyi; Jevtovic-Todorovic, Vesna; Li, Xudong","year":2017,"journal":"Nanomedicine : nanotechnology, biology, and medicine, 13(6), 2049-2059","doi":"10.1016/j.nano.2017.03.015","pmid":"28404518","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In a mouse radiculopathy model, fullerol at 10 or 100 μM counteracted pain sensitization and inflammatory responses when disc material was pretreated before implantation. While macrophage infiltration (IBA1+) was similar across groups, IL-1β and IL-6 expression was decreased in the fullerol-treated group.\n\nIn dorsal root ganglion (DRG) explant cultures treated with TNF-α, fullerol significantly reversed the increased expression of IL-1β, NLRP3, and caspase 1, identifying the NLRP3 inflammasome as a key target. Critically, fullerol also decreased expression of the pain neuropeptides substance P and CGRP in cultured DRGs, explaining its analgesic effect.","whyItMatters":"Radiculopathy from disc degeneration is a major cause of chronic pain with limited treatment options — NSAIDs have side effects and opioids carry addiction risk. Fullerol targets the pain at multiple levels: reducing inflammation via the NLRP3 inflammasome and lowering pain-amplifying neuropeptides substance P and CGRP. This multi-target approach could offer advantages over single-pathway pain drugs.","specificNumbers":"","methodology":"The study used two complementary models: a mouse radiculopathy model where disc material was bathed in fullerol (10 or 100 μM) before being surgically implanted near nerve roots, and an ex vivo dorsal root ganglion explant culture stimulated with TNF-α. Pain behavior was assessed in vivo, and inflammatory and neuropeptide markers were measured by immunohistochemistry and molecular analysis.","limitations":"This is a preclinical study in mice and cell culture with no human data. The fullerol was applied as a pretreatment to disc material before implantation, which doesn't mirror how a drug would be delivered to patients with existing disc disease. Specific dosing for clinical use and long-term safety of nanoparticle fullerol administration are not addressed. The mechanism by which fullerol reaches and acts on DRG neurons in vivo needs clarification."},{"rthcId":"RPEP-03336","title":"Potent peptidic fusion inhibitors of influenza virus.","authors":"Kadam, Rameshwar U; Juraszek, Jarek; Brandenburg, Boerries; Buyck, Christophe; Schepens, Wim B G; Kesteleyn, Bart; Stoops, Bart; Vreeken, Rob J; Vermond, Jan; Goutier, Wouter; Tang, Chan; Vogels, Ronald; Friesen, Robert H E; Goudsmit, Jaap; van Dongen, Maria J P; Wilson, Ian A","year":2017,"journal":"Science (New York, N.Y.), 358(6362), 496-502","doi":"10.1126/science.aan0516","pmid":"28971971","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03337","title":"Restoring effects of oxytocin on the attentional preference for faces in autism.","authors":"Kanat, M; Spenthof, I; Riedel, A; van Elst, L T; Heinrichs, M; Domes, G","year":2017,"journal":"Translational psychiatry, 7(4), e1097","doi":"10.1038/tp.2017.67","pmid":"28418399","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03338","title":"Effects of semaglutide on beta cell function and glycaemic control in participants with type 2 diabetes: a randomised, double-blind, placebo-controlled trial.","authors":"Kapitza, Christoph; Dahl, Kirsten; Jacobsen, Jacob B; Axelsen, Mads B; Flint, Anne","year":2017,"journal":"Diabetologia, 60(8), 1390-1399","doi":"10.1007/s00125-017-4289-0","pmid":"28526920","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In a randomized, double-blind, placebo-controlled trial of 75 adults with type 2 diabetes, 12 weeks of once-weekly semaglutide (1.0 mg) significantly improved beta cell function. First-phase insulin secretion tripled (treatment ratio 3.02, 95% CI 2.53–3.60) and second-phase insulin secretion doubled (treatment ratio 2.10, 95% CI 1.86–2.37) compared to placebo, both P<0.0001. Semaglutide also significantly reduced 24-hour glucose and glucagon responses (P<0.0001), and an arginine stimulation test showed increased maximal insulin capacity. Remarkably, during a graded glucose infusion test, semaglutide restored insulin secretion rates to levels similar to those seen in healthy participants without diabetes.","whyItMatters":"Type 2 diabetes is fundamentally a disease of declining beta cell function. This study provides rigorous evidence that semaglutide doesn't just lower blood sugar — it actually improves the pancreas's ability to produce insulin in response to glucose. The finding that insulin secretion rates were restored to near-healthy levels suggests semaglutide may help preserve or partially reverse the core defect in type 2 diabetes, not just treat its symptoms.","specificNumbers":"n=75 · 37 semaglutide, 38 placebo · First-phase insulin 3.02x placebo · Second-phase insulin 2.10x placebo · Both P<0.0001 · 12 weeks · 1.0 mg once weekly","methodology":"Randomized, double-blind, placebo-controlled, parallel-group trial at a single center in Germany. 75 adults with T2DM (HbA1c 6.5–9.0%, BMI 20–35 kg/m²) were randomized 1:1 to once-weekly subcutaneous semaglutide (escalated from 0.25 to 0.5 to 1.0 mg) or placebo for 12 weeks. Beta cell function was assessed using intravenous glucose tolerance test (IVGTT), arginine stimulation test, 24-hour meal stimulation test, and graded glucose infusion test. A group of healthy untreated participants served as a reference for the glucose infusion test.","limitations":"Small sample of 75 participants at a single center. Twelve-week duration doesn't address whether beta cell improvements persist long-term or after discontinuation. Funded by Novo Nordisk (semaglutide's manufacturer). Participants had relatively well-controlled diabetes (HbA1c 6.5–9.0%), so results may not apply to more advanced disease. Escalating dose makes it difficult to attribute effects to a specific dose level."},{"rthcId":"RPEP-03339","title":"Duodenal-jejunal bypass changes the composition of the gut microbiota.","authors":"Kashihara, Hideya; Shimada, Mitsuo; Yoshikawa, Kozo; Higashijima, Jun; Nakao, Toshihiro; Nishi, Masaaki; Takasu, Chie","year":2017,"journal":"Surgery today, 47(1), 137-140","doi":null,"pmid":"27412617","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03340","title":"Peptide Selank Enhances the Effect of Diazepam in Reducing Anxiety in Unpredictable Chronic Mild Stress Conditions in Rats.","authors":"Kasian, Anastasiya; Kolomin, Timur; Andreeva, Lyudmila; Bondarenko, Elena; Myasoedov, Nikolay; Slominsky, Petr; Shadrina, Maria","year":2017,"journal":"Behavioural neurology, 2017, 5091027","doi":"10.1155/2017/5091027","pmid":"28280289","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03341","title":"Kisspeptin as a promising oocyte maturation trigger for in vitro fertilisation in humans.","authors":"Kasum, Miro; Franulić, Daniela; Čehić, Ermin; Orešković, Slavko; Lila, Albert; Ejubović, Emina","year":2017,"journal":"Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology, 33(8), 583-587","doi":"10.1080/09513590.2017.1309019","pmid":"28393578","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03342","title":"Neuropeptide Y, resilience, and PTSD therapeutics.","authors":"Kautz, Marin; Charney, Dennis S; Murrough, James W","year":2017,"journal":"Neuroscience letters, 649, 164-169","doi":"10.1016/j.neulet.2016.11.061","pmid":"27913193","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03343","title":"Effects of cerebrolysin on functional recovery in patients with severe disability after traumatic brain injury: A historical cohort study.","authors":"Khalili, Hosseinali; Niakan, Amin; Ghaffarpasand, Fariborz","year":2017,"journal":"Clinical neurology and neurosurgery, 152, 34-38","doi":"10.1016/j.clineuro.2016.11.011","pmid":"27871029","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03344","title":"Lactam-Stapled Cell-Penetrating Peptides: Cell Uptake and Membrane Binding Properties.","authors":"Klein, Marco J; Schmidt, Samuel; Wadhwani, Parvesh; Bürck, Jochen; Reichert, Johannes; Afonin, Sergii; Berditsch, Marina; Schober, Tim; Brock, Roland; Kansy, Manfred; Ulrich, Anne S","year":2017,"journal":"Journal of medicinal chemistry, 60(19), 8071-8082","doi":"10.1021/acs.jmedchem.7b00813","pmid":"28921993","tags":["cell-penetrating-peptides","peptide-stapling","drug-delivery"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Researchers tested whether lactam stapling — a chemical modification that locks peptides into a helical shape — improves cell-penetrating peptide (CPP) performance. The results were mixed: of four stapled peptides tested, only one (MAP-1) showed clear improvement. Stapling MAP-1 enhanced its helical structure in both water and lipid environments, eliminated membrane leakage (a proxy for toxicity), and maintained high cellular uptake in HEK293 and HeLa cells.\n\nThe other three peptides (DRIM, WWSP, KFGF) didn't improve with stapling. Critically, the study found that a CPP's ability to enter cells correlates with how helical it becomes when interacting with membranes — not how helical it is free in solution. Nearly all stapled peptides caused less membrane damage (less vesicle leakage, hemolysis, and bacterial lysis) than their linear versions.","whyItMatters":"Cell-penetrating peptides are key tools for delivering drugs into cells, but they often damage cell membranes in the process. This study shows that stapling can reduce toxicity, but its effect on cell entry depends heavily on the specific peptide. The finding that membrane-bound helicity (not solution helicity) predicts uptake efficiency is an important design principle for engineering better drug delivery peptides.","specificNumbers":"4 stapled peptides vs 4 linear counterparts · MAP-1: eliminated leakage + maintained uptake · 3 other peptides: no improvement · Tested in HEK293 + HeLa cells · Reduced hemolysis across most stapled variants","methodology":"In vitro comparison of four lactam-stapled cell-penetrating peptides against their linear (unstapled) counterparts. Measured membrane binding, conformational behavior (circular dichroism), vesicle leakage, hemolysis, bacterial lysis, and cellular uptake in HEK293 and HeLa cells. Correlated structural features with functional outcomes.","limitations":"In vitro study only — cell uptake in culture dishes may not predict in vivo drug delivery performance. Only four peptide systems tested, limiting generalizability. The success of stapling was peptide-dependent, making it hard to predict which CPPs will benefit from this modification without testing each one individually."},{"rthcId":"RPEP-03345","title":"Stabilized helical peptides: overview of the technologies and its impact on drug discovery.","authors":"Klein, Mark","year":2017,"journal":"Expert opinion on drug discovery, 12(11), 1117-1125","doi":"10.1080/17460441.2017.1372745","pmid":"28889766","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03346","title":"Screening for proteolytically active lactic acid bacteria and bioactivity of peptide hydrolysates obtained with selected strains.","authors":"Kliche, T; Li, B; Bockelmann, W; Habermann, D; Klempt, M; de Vrese, M; Wutkowski, A; Clawin-Raedecker, I; Heller, K J","year":2017,"journal":"Applied microbiology and biotechnology, 101(20), 7621-7633","doi":"10.1007/s00253-017-8369-3","pmid":"28695230","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03347","title":"Gene electrotransfer into skin using noninvasive multi-electrode array for vaccination and wound healing.","authors":"Kos, Spela; Vanvarenberg, Kevin; Dolinsek, Tanja; Cemazar, Maja; Jelenc, Jure; Préat, Véronique; Sersa, Gregor; Vandermeulen, Gaëlle","year":2017,"journal":"Bioelectrochemistry (Amsterdam, Netherlands), 114, 33-41","doi":"10.1016/j.bioelechem.2016.12.002","pmid":"28006672","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03348","title":"Endocannabinoids inhibit neurogenic inflammation in murine joints by a non-canonical cannabinoid receptor mechanism.","authors":"Krustev, Eugene; Muley, Milind M; McDougall, Jason J","year":2017,"journal":"Neuropeptides, 64, 131-135","doi":"10.1016/j.npep.2016.08.007","pmid":"27567396","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03349","title":"Structure-Based Design of Non-natural Macrocyclic Peptides That Inhibit Protein-Protein Interactions.","authors":"Krüger, Dennis M; Glas, Adrian; Bier, David; Pospiech, Nicole; Wallraven, Kerstin; Dietrich, Laura; Ottmann, Christian; Koch, Oliver; Hennig, Sven; Grossmann, Tom N","year":2017,"journal":"Journal of medicinal chemistry, 60(21), 8982-8988","doi":"10.1021/acs.jmedchem.7b01221","pmid":"29028171","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03350","title":"Designer vaccine nanodiscs for personalized cancer immunotherapy.","authors":"Kuai, Rui; Ochyl, Lukasz J; Bahjat, Keith S; Schwendeman, Anna; Moon, James J","year":2017,"journal":"Nature materials, 16(4), 489-496","doi":"10.1038/nmat4822","pmid":"28024156","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03351","title":"Cancer immunotherapy: moving forward with peptide T cell vaccines.","authors":"Kumai, Takumi; Fan, Aaron; Harabuchi, Yasuaki; Celis, Esteban","year":2017,"journal":"Current opinion in immunology, 47, 57-63","doi":"10.1016/j.coi.2017.07.003","pmid":"28734176","tags":[],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Peptide-based cancer vaccines have historically underperformed in clinical trials, largely because they produced weak immune responses and couldn't overcome the tumor's ability to suppress the immune system. However, the success of immune checkpoint inhibitors (like PD-1 blockers) has reinvigorated the field by showing that T cells really can fight cancer — they just need the right activation.\n\nThe authors describe optimized approaches to peptide vaccine design, including better antigen selection (choosing the right tumor protein fragments), improved adjuvants (immune-boosting additives), and smarter administration strategies. These advances aim to generate more powerful tumor-reactive T cell responses that can work alongside checkpoint inhibitors.","whyItMatters":"Cancer immunotherapy has been transformed by checkpoint inhibitors, but these drugs only work well in patients who already have some immune response against their tumor. Peptide vaccines could fill this gap by training the immune system to recognize specific tumor targets. If optimized vaccine strategies can reliably generate strong T cell responses, they could make checkpoint inhibitors effective for a much larger group of cancer patients.","specificNumbers":"Review covers multiple vaccine strategies · Focus on antigen/adjuvant optimization · Discusses combination with checkpoint inhibitors","methodology":"This is an expert review summarizing the history, challenges, and recent advances in peptide-based T cell cancer vaccines. The authors draw on published clinical trial data, preclinical research, and their own laboratory experience developing optimized antigen selection, adjuvant formulations, and vaccine delivery methods.","limitations":"As a review, this paper does not present new clinical data. The optimized vaccine strategies described are largely based on preclinical models and early-stage research, and may not translate directly to clinical success. The field of cancer vaccines has a history of promising preclinical results that failed in human trials, so cautious interpretation is warranted."},{"rthcId":"RPEP-03352","title":"Design, synthesis of allosteric peptide activator for human SIRT1 and its biological evaluation in cellular model of Alzheimer's disease.","authors":"Kumar, Rahul; Nigam, Lokesh; Singh, Amrendra Pratap; Singh, Kusum; Subbarao, Naidu; Dey, Sharmistha","year":2017,"journal":"European journal of medicinal chemistry, 127, 909-916","doi":"10.1016/j.ejmech.2016.11.001","pmid":"27836195","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The tripeptide CWR (Cys-Trp-Arg) was identified through molecular docking and demonstrated multiple levels of SIRT1 activation:\n\n- Biochemical: Enhanced activity of purified recombinant SIRT1 by lowering the Michaelis constant (Km), indicating an allosteric activation mechanism\n- Clinical relevance: Increased SIRT1 activity in serum from Alzheimer's disease patients\n- Cellular: Decreased acetylation of p53 (a SIRT1 substrate) in IMR-32 neuroblastoma cells, confirming intracellular SIRT1 activation\n- Neuroprotection: Protected neuronal cells from amyloid-beta fragment-induced cell death (MTT assay)\n\nThe peptide works allosterically — binding at a site different from the active site to enhance enzyme activity.","whyItMatters":"SIRT1 activation is one of the most studied strategies in anti-aging and neuroprotection research — it's the enzyme activated by resveratrol (red wine compound) and caloric restriction. Most SIRT1 activators are small molecules, not peptides. This study demonstrates that a simple tripeptide can effectively activate SIRT1 and protect brain cells, opening a new avenue for peptide-based Alzheimer's therapeutics. The finding that CWR works on SIRT1 in actual Alzheimer's patient serum adds clinical relevance.","specificNumbers":"","methodology":"Tripeptide candidates were screened using molecular docking against SIRT1's crystal structure. The selected peptide CWR was synthesized by solid-phase peptide synthesis. SIRT1 activation was measured by Fluorescent Activity Assay using purified recombinant SIRT1 and serum from AD patients. Kinetic analysis (Km determination) characterized the activation mechanism. Intracellular SIRT1 activity was assessed by measuring acetylated p53 levels in IMR-32 neuroblastoma cells. Neuroprotection was evaluated using MTT cell viability assay after amyloid-beta fragment treatment.","limitations":"This is an early-stage proof-of-concept study with only in vitro and cell culture data — no animal or human treatment studies. The tripeptide's stability, bioavailability, blood-brain barrier penetration, and in vivo efficacy have not been tested. Cell line models (IMR-32 neuroblastoma) don't fully represent the complex brain environment in Alzheimer's. The serum SIRT1 activation assay is promising but doesn't confirm the peptide reaches the brain. Potential off-target effects of CWR were not assessed."},{"rthcId":"RPEP-03353","title":"Effect of N- and C-Terminal Modifications on Cytotoxic Properties of Antimicrobial Peptide Tachyplesin I.","authors":"Kuzmin, D V; Emelianova, A A; Kalashnikova, M B; Panteleev, P V; Ovchinnikova, T V","year":2017,"journal":"Bulletin of experimental biology and medicine, 162(6), 754-757","doi":"10.1007/s10517-017-3705-2","pmid":"28429216","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Adding chemical caps to both ends of the antimicrobial peptide tachyplesin I (N-terminal acetylation and C-terminal amidation) increased its cell-killing potency against tumor cells and made it resistant to enzymatic breakdown in human serum. However, the modifications also increased toxicity toward normal cells and red blood cells (hemolysis), presenting a double-edged sword for anticancer development.","whyItMatters":"Antimicrobial peptides like tachyplesin I are promising anticancer candidates, but they break down too quickly in the bloodstream to be practical drugs. This study shows that simple chemical modifications can solve the stability problem — the modified peptide resisted degradation in human serum. The challenge is that the same modifications that make it more potent also make it less selective for cancer cells.","specificNumbers":"","methodology":"In vitro study using MTT cell viability assays on tumor cell lines (A549, HeLa) and normal human cells (HEK293), plus hemolysis assays on human red blood cells. Proteolytic stability was tested by incubating modified and unmodified peptides in fresh human serum.","limitations":"Entirely in vitro — no animal or human testing. Increased toxicity to normal cells is a significant concern that would need to be addressed before any clinical development. Specific IC50 values and fold-changes in cytotoxicity are not provided in the abstract."},{"rthcId":"RPEP-03354","title":"Effects of an Antagonistic Analog of Growth Hormone-Releasing Hormone on Endometriosis in a Mouse Model and In Vitro.","authors":"Köster, Frank; Jin, Li; Shen, Yuanming; Schally, Andrew V; Cai, Ren-Zhi; Block, Norman L; Hornung, Daniela; Marschner, Gabriele; Rody, Achim; Engel, Jörg B; Finas, Dominique","year":2017,"journal":"Reproductive sciences (Thousand Oaks, Calif.), 24(11), 1503-1511","doi":"10.1177/1933719117691140","pmid":"28205459","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The GHRH receptor splice variant SV1 was detected in human endometrial tissue, with the highest expression found in the uterine lining of patients who had endometriosis (eutopic endometrium) compared to the endometriosis lesions themselves (ectopic tissue) or normal endometrium. Interestingly, GHRH itself was most highly expressed in ectopic endometriosis lesions.\n\nIn the mouse model, daily treatment with 10 μg MIA-602 resulted in significantly smaller human endometrial xenotransplants after 4 weeks compared to vehicle-treated controls. In cell culture, 1 μM MIA-602 decreased proliferation of endometrial stromal cells and two endometriosis cell lines (12-Z and 49-Z) after 72 hours. The drug reduced epidermal growth factor receptor protein levels and decreased activation of the MAP kinases ERK-1/2, identifying a specific signaling mechanism.","whyItMatters":"Endometriosis affects an estimated 10% of reproductive-age women and current treatments — hormonal suppression and surgery — have significant limitations and side effects. Finding that endometriosis tissue expresses GHRH receptors opens a completely new treatment target. A peptide antagonist that can shrink endometriosis by blocking growth signaling could offer an alternative to hormonal therapy without the same endocrine side effects.","specificNumbers":"","methodology":"The study combined in vitro and in vivo approaches. Researchers first confirmed GHRH receptor SV1 expression in human endometrial tissue using Western blots and qRT-PCR. They then tested MIA-602 in a mouse xenotransplant model where human endometrial tissue from endometriosis patients was implanted into mice. Cell culture experiments used endometrial stromal cells and two established endometriosis cell lines (12-Z and 49-Z) to measure proliferation and signaling pathway changes.","limitations":"This is a preclinical study using a mouse xenotransplant model, which may not fully replicate human endometriosis. The mouse model uses immunodeficient (nude) mice, removing the immune component of the disease. Sample sizes for human tissue analysis are not specified. The drug has not been tested in human clinical trials for endometriosis. Long-term effects and side effects of GHRH antagonism are unknown. The endometriosis cell lines used may not perfectly represent all forms of the disease."},{"rthcId":"RPEP-03355","title":"Sensory neuron regulation of gastrointestinal inflammation and bacterial host defence.","authors":"Lai, N Y; Mills, K; Chiu, I M","year":2017,"journal":"Journal of internal medicine, 282(1), 5-23","doi":"10.1111/joim.12591","pmid":"28155242","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03356","title":"N-Arachidonoyl Dopamine Modulates Acute Systemic Inflammation via Nonhematopoietic TRPV1.","authors":"Lawton, Samira K; Xu, Fengyun; Tran, Alphonso; Wong, Erika; Prakash, Arun; Schumacher, Mark; Hellman, Judith; Wilhelmsen, Kevin","year":2017,"journal":"Journal of immunology (Baltimore, Md. : 1950), 199(4), 1465-1475","doi":"10.4049/jimmunol.1602151","pmid":"28701511","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03357","title":"Enzymatic Cross-Linking of Side Chains Generates a Modified Peptide with Four Hairpin-like Bicyclic Repeats.","authors":"Lee, Hyunbin; Park, Youngseon; Kim, Seokhee","year":2017,"journal":"Biochemistry, 56(37), 4927-4930","doi":"10.1021/acs.biochem.7b00808","pmid":"28841794","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03358","title":"Oxytocin and Serotonin Brain Mechanisms in the Nonhuman Primate.","authors":"Lefevre, Arthur; Richard, Nathalie; Jazayeri, Mina; Beuriat, Pierre-Aurélien; Fieux, Sylvain; Zimmer, Luc; Duhamel, Jean-René; Sirigu, Angela","year":2017,"journal":"The Journal of neuroscience : the official journal of the Society for Neuroscience, 37(28), 6741-6750","doi":"10.1523/JNEUROSCI.0659-17.2017","pmid":"28607170","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03359","title":"A Practical Review of C-Peptide Testing in Diabetes.","authors":"Leighton, Emma; Sainsbury, Christopher Ar; Jones, Gregory C","year":2017,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 8(3), 475-487","doi":"10.1007/s13300-017-0265-4","pmid":"28484968","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"C-peptide is produced in equal amounts to insulin but is excreted more steadily, making it a reliable marker of how much insulin the pancreas is actually producing. A C-peptide level below 0.2 nmol/L is strongly associated with a diagnosis of type 1 diabetes. The authors recommend glucagon stimulation testing as the best balance of sensitivity and practicality among available methods. C-peptide levels also correlate with microvascular and macrovascular complications, future need for insulin therapy, and likely response to individual treatments.","whyItMatters":"Many people with diabetes receive an uncertain diagnosis — especially those who develop diabetes later in life but may actually have type 1 or latent autoimmune diabetes. C-peptide testing can clarify what type of diabetes someone has, predict complications, and guide treatment decisions. This review consolidates the evidence into practical recommendations clinicians can use.","specificNumbers":"","methodology":"The authors conducted a narrative review of the published literature on C-peptide testing methods, including urinary C-peptide, unstimulated serum C-peptide, and stimulated serum C-peptide (via glucagon stimulation test). They evaluated the sensitivity, practicality, and clinical utility of each approach.","limitations":"As a narrative review rather than a systematic review or meta-analysis, the paper does not quantitatively pool data from multiple studies. The specific cutoff values cited may vary depending on the assay used and the population studied. The review focuses primarily on clinical utility rather than exploring emerging research applications of C-peptide measurement."},{"rthcId":"RPEP-03360","title":"Vasoactive Intestinal Peptide Protects Salivary Glands against Structural Injury and Secretory Dysfunction via IL-17A and AQP5 Regulation in a Model of Sjögren Syndrome.","authors":"Li, Chengyin; Zhu, Fenglin; Wu, Bin; Wang, Yue","year":2017,"journal":"Neuroimmunomodulation, 24(6), 300-309","doi":"10.1159/000486859","pmid":"29617700","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03361","title":"Neuropeptide VGF C-Terminal Peptide TLQP-62 Alleviates Lipopolysaccharide-Induced Memory Deficits and Anxiety-like and Depression-like Behaviors in Mice: The Role of BDNF/TrkB Signaling.","authors":"Li, Chenli; Li, Mengmeng; Yu, Hanjie; Shen, Xinbei; Wang, Jinting; Sun, Xin; Wang, Qinwen; Wang, Chuang","year":2017,"journal":"ACS chemical neuroscience, 8(9), 2005-2018","doi":"10.1021/acschemneuro.7b00154","pmid":"28594546","tags":[],"studyType":"animal","evidenceStrength":"early","keyFinding":"The neuropeptide fragment TLQP-62 (derived from the VGF protein) prevented inflammation-induced memory deficits, depression-like behavior, and anxiety-like behavior in mice when injected into the brain before an inflammatory challenge (LPS). TLQP-62 also reduced neuroinflammation and oxidative stress markers. Critically, when BDNF expression was knocked down using a viral vector, TLQP-62's protective effects were blocked — demonstrating that the peptide works through the BDNF/TrkB signaling pathway.","whyItMatters":"Neuroinflammation is increasingly recognized as a driver of depression, anxiety, and cognitive decline. This study identifies a specific neuropeptide (TLQP-62) that can protect against inflammation-induced brain dysfunction through BDNF signaling — a pathway already known to be central to antidepressant action. It suggests peptide-based approaches could offer a new therapeutic angle for neuropsychiatric conditions linked to inflammation.","specificNumbers":"TLQP-62: 2 μg/side i.c.v. · LPS: 0.5 mg/kg i.p. · Prevented recognition memory deficits · Prevented depression-like behavior · Prevented anxiety-like behavior · Effects blocked by BDNF knockdown","methodology":"ICR mice received intracerebroventricular injection of TLQP-62 (2 μg/side) 1 hour before intraperitoneal LPS (0.5 mg/kg) to model inflammation-induced neuropsychiatric dysfunction. Behavioral tests included novel object recognition (memory), forced swim test and sucrose preference test (depression), and elevated zero maze (anxiety). Neuroinflammation and oxidative stress markers were measured. BDNF-shRNA lentivirus was used to knock down BDNF and test whether TLQP-62's effects depended on BDNF/TrkB signaling.","limitations":"Mouse study with invasive brain injection — not translatable to practical therapy. Single pretreatment design does not show whether the peptide works after inflammation has already started. The LPS model is a simplified acute inflammation model that may not replicate chronic neuroinflammatory conditions. TLQP-62 cannot cross the blood-brain barrier in its current form."},{"rthcId":"RPEP-03362","title":"Removable Backbone Modification Method for the Chemical Synthesis of Membrane Proteins.","authors":"Li, Jia-Bin; Tang, Shan; Zheng, Ji-Shen; Tian, Chang-Lin; Liu, Lei","year":2017,"journal":"Accounts of chemical research, 50(5), 1143-1153","doi":"10.1021/acs.accounts.7b00001","pmid":"28374993","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03363","title":"Endogenously Released Neuropeptide Y Suppresses Hippocampal Short-Term Facilitation and Is Impaired by Stress-Induced Anxiety.","authors":"Li, Qin; Bartley, Aundrea F; Dobrunz, Lynn E","year":2017,"journal":"The Journal of neuroscience : the official journal of the Society for Neuroscience, 37(1), 23-37","doi":"10.1523/JNEUROSCI.2599-16.2016","pmid":"28053027","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03364","title":"Controlled release of BSA-linked cisplatin through a PepGel self-assembling peptide nanofiber hydrogel scaffold.","authors":"Liang, Jun; Liu, Gang; Wang, Jing; Sun, Xiuzhi Susan","year":2017,"journal":"Amino acids, 49(12), 2015-2021","doi":"10.1007/s00726-017-2444-z","pmid":"28603803","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"PepGel (h9e peptide) formed a hydrogel triggered by BSA-linked cisplatin (BSA-CP), with BSA-CP serving dual roles as gelation trigger and drug payload. Fluorescence studies showed strong interaction between PepGel and BSA's hydrophobic subdomain. TEM and confocal microscopy confirmed BSA-CP dispersal within PepGel nanofibers with enhanced fiber aggregation. PepGel effectively inhibited BSA-CP diffusion even at concentrations below 0.3 wt%. Drug release rate was controllable by adjusting PepGel concentration. HeLa cell viability data was consistent with drug release kinetics, confirming maintained anti-cancer activity.","whyItMatters":"Local, sustained delivery of chemotherapy could reduce the severe systemic side effects that make cisplatin treatment so difficult for patients. An injectable peptide gel that can be administered through a syringe and slowly releases drug at the tumor site is a practical approach. The ability to tune release rate by adjusting gel concentration gives clinicians control over drug delivery kinetics.","specificNumbers":"","methodology":"PepGel concentration was varied to study effects on BSA-CP release kinetics. Fluorescence spectroscopy assessed PepGel-BSA interactions (tryptophan quenching). TEM and fluorescence confocal microscopy visualized drug distribution within nanofiber networks. UV spectroscopy measured BSA-CP release rates at different PepGel concentrations. HeLa cell culture assessed cytotoxicity correlating with drug release data.","limitations":"In vitro study only — no animal tumor models were used. BSA-linked cisplatin may behave differently from clinical cisplatin formulations. Only HeLa cells were tested, limiting generalizability to different tumor types. The study didn't assess gel stability, degradation, or drug release in physiological conditions with enzymes. Long-term biocompatibility and immunogenicity of the peptide gel in vivo were not evaluated. The release kinetics were measured in simple buffer, not in tissue-like environments."},{"rthcId":"RPEP-03365","title":"Phase I/IIa clinical trial of a novel hTERT peptide vaccine in men with metastatic hormone-naive prostate cancer.","authors":"Lilleby, Wolfgang; Gaudernack, Gustav; Brunsvig, Paal F; Vlatkovic, Ljiljana; Schulz, Melanie; Mills, Kate; Hole, Knut Håkon; Inderberg, Else Marit","year":2017,"journal":"Cancer immunology, immunotherapy : CII, 66(7), 891-901","doi":"10.1007/s00262-017-1994-y","pmid":"28391357","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03366","title":"A neuropeptide, Substance-P, directly induces tissue-repairing M2 like macrophages by activating the PI3K/Akt/mTOR pathway even in the presence of IFNγ.","authors":"Lim, Ji Eun; Chung, Eunkyung; Son, Youngsook","year":2017,"journal":"Scientific reports, 7(1), 9417","doi":"10.1038/s41598-017-09639-7","pmid":"28842601","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03367","title":"Activation of NPFFR2 leads to hyperalgesia through the spinal inflammatory mediator CGRP in mice.","authors":"Lin, Ya-Tin; Liu, Ho-Ling; Day, Yuan-Ji; Chang, Che-Chien; Hsu, Po-Hung; Chen, Jin-Chung","year":2017,"journal":"Experimental neurology, 291, 62-73","doi":"10.1016/j.expneurol.2017.02.003","pmid":"28179153","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03368","title":"NPFFR2 Activates the HPA Axis and Induces Anxiogenic Effects in Rodents.","authors":"Lin, Ya-Tin; Yu, Yu-Lian; Hong, Wei-Chen; Yeh, Ting-Shiuan; Chen, Ting-Chun; Chen, Jin-Chung","year":2017,"journal":"International journal of molecular sciences, 18(8)","doi":"10.3390/ijms18081810","pmid":"28825666","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"NPFFR2 agonists (dNPA administered ICV and AC-263093 administered IP) increased serum corticosteroid levels in a time-dependent manner (rats) and dose-dependent manner (mice). These effects were blocked by:\n\n- RF9 (NPFF receptor antagonist, ICV)\n- α-helical CRF(9-41) (CRF receptor antagonist, IV)\n\nAC-263093 also increased c-Fos expression in the hypothalamic paraventricular nucleus (confirming neuronal activation in the HPA axis command center) and induced anxiogenic effects in mice on the elevated plus maze. This is the first demonstration that NPFFR2 directly activates the HPA axis and triggers anxiety-like behaviors.","whyItMatters":"The HPA stress axis is central to anxiety disorders, depression, and PTSD. Most research has focused on CRF as the primary driver of this axis. Discovering that NPFFR2 — a receptor for a completely different neuropeptide family — can independently activate the HPA axis opens a new therapeutic target. NPFFR2 antagonists could potentially reduce pathological stress responses without the issues associated with directly blocking the CRF system.","specificNumbers":"","methodology":"NPFFR2 agonists were administered to rats (ICV, intracerebroventricularly) and mice (IP, intraperitoneally). Serum corticosteroid levels were measured at multiple time points and doses. Receptor specificity was confirmed using the NPFF receptor antagonist RF9 and the CRF antagonist α-helical CRF(9-41). c-Fos immunohistochemistry assessed neuronal activation in the hypothalamic paraventricular nucleus. Anxiety-like behavior was evaluated using the elevated plus maze in mice.","limitations":"This is a preclinical study in rodents — direct translation to human anxiety and stress disorders is uncertain. The pharmacological tools (agonists and antagonists) may not be perfectly selective for NPFFR2. The elevated plus maze measures anxiety-like behavior but does not directly assess the subjective experience of anxiety. The CRF antagonist blockade suggests NPFFR2 works upstream of CRF, but the precise neural circuit was not fully mapped."},{"rthcId":"RPEP-03369","title":"Overlooked Short Toxin-Like Proteins: A Shortcut to Drug Design.","authors":"Linial, Michal; Rappoport, Nadav; Ofer, Dan","year":2017,"journal":"Toxins, 9(11)","doi":"10.3390/toxins9110350","pmid":"29109389","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03370","title":"The Primary Mechanism of Cellular Internalization for a Short Cell- Penetrating Peptide as a Nano-Scale Delivery System.","authors":"Liu, Betty R; Huang, Yue-Wern; Korivi, Mallikarjuna; Lo, Shih-Yen; Aronstam, Robert S; Lee, Han-Jung","year":2017,"journal":"Current pharmaceutical biotechnology, 18(7), 569-584","doi":"10.2174/1389201018666170822125737","pmid":"28828981","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03371","title":"Ghrelin accelerates wound healing in combined radiation and wound injury in mice.","authors":"Liu, Cong; Hao, Yuhui; Huang, Jiawei; Li, Hong; Yang, Zhangyou; Zeng, Yiping; Liu, Jing; Li, Rong","year":2017,"journal":"Experimental dermatology, 26(2), 186-193","doi":"10.1111/exd.13224","pmid":"27676309","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03372","title":"PSSMHCpan: a novel PSSM-based software for predicting class I peptide-HLA binding affinity.","authors":"Liu, Geng; Li, Dongli; Li, Zhang; Qiu, Si; Li, Wenhui; Chao, Cheng-Chi; Yang, Naibo; Li, Handong; Cheng, Zhen; Song, Xin; Cheng, Le; Zhang, Xiuqing; Wang, Jian; Yang, Huanming; Ma, Kun; Hou, Yong; Li, Bo","year":2017,"journal":"GigaScience, 6(5), 1-11","doi":"10.1093/gigascience/gix017","pmid":"28327987","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03373","title":"Tumor-targeting peptides from combinatorial libraries.","authors":"Liu, Ruiwu; Li, Xiaocen; Xiao, Wenwu; Lam, Kit S","year":2017,"journal":"Advanced drug delivery reviews, 110-111, 13-37","doi":"10.1016/j.addr.2016.05.009","pmid":"27210583","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03374","title":"Cross-Linking Approaches to Tuning the Mechanical Properties of Peptide π-Electron Hydrogels.","authors":"Liyanage, Wathsala; Ardoña, Herdeline Ann M; Mao, Hai-Quan; Tovar, John D","year":2017,"journal":"Bioconjugate chemistry, 28(3), 751-759","doi":"10.1021/acs.bioconjchem.6b00593","pmid":"28292179","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03375","title":"Chronic stress leads to epigenetic dysregulation in the neuropeptide-Y and cannabinoid CB1 receptor genes in the mouse cingulate cortex.","authors":"Lomazzo, Ermelinda; König, Florian; Abassi, Leila; Jelinek, Ruth; Lutz, Beat","year":2017,"journal":"Neuropharmacology, 113(Pt A), 301-313","doi":"10.1016/j.neuropharm.2016.10.008","pmid":"27737789","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03376","title":"Glucagon-like Peptide-1 Receptor Agonists: A Class Update for Treating Type 2 Diabetes.","authors":"Lovshin, Julie A","year":2017,"journal":"Canadian journal of diabetes, 41(5), 524-535","doi":"10.1016/j.jcjd.2017.08.242","pmid":"28942790","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03377","title":"TCR-like antibody drug conjugates mediate killing of tumor cells with low peptide/HLA targets.","authors":"Lowe, Devin B; Bivens, Camille K; Mobley, Alexis S; Herrera, Christian E; McCormick, Amanda L; Wichner, Timea; Sabnani, Manoj K; Wood, Laurence M; Weidanz, Jon A","year":2017,"journal":"mAbs, 9(4), 603-614","doi":"10.1080/19420862.2017.1302630","pmid":"28273004","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03378","title":"A novel multi-epitope vaccine from MMSA-1 and DKK1 for multiple myeloma immunotherapy.","authors":"Lu, Chenyang; Meng, Shan; Jin, Yanxia; Zhang, Wanggang; Li, Zongfang; Wang, Fang; Wang-Johanning, Feng; Wei, Yongchang; Liu, Hailing; Tu, Honglei; Su, Dan; He, Aili; Cao, Xingmei; Zhou, Fuling","year":2017,"journal":"British journal of haematology, 178(3), 413-426","doi":"10.1111/bjh.14686","pmid":"28508448","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03379","title":"The host defense peptide LL-37 a possible inducer of the type I interferon system in patients with polymyositis and dermatomyositis.","authors":"Lu, Xin; Tang, Quan; Lindh, Monica; Dastmalchi, Maryam; Alexanderson, Helene; Popovic Silwerfeldt, Karin; Agerberth, Birgitta; Lundberg, Ingrid E; Wick, Cecilia","year":2017,"journal":"Journal of autoimmunity, 78, 46-56","doi":"10.1016/j.jaut.2016.12.003","pmid":"28012697","tags":[],"studyType":"observational","evidenceStrength":"early","keyFinding":"The antimicrobial peptide LL-37 was elevated in muscle tissue of patients with polymyositis (PM) and dermatomyositis (DM) compared to healthy controls, primarily released by infiltrating neutrophils. Plasmacytoid dendritic cells (BDCA-2+, the main type I interferon producers) and the interferon marker MxA were also elevated in affected muscle. All PM/DM patients with short disease duration had low vitamin D levels. The findings support the hypothesis that LL-37 may trigger the type I interferon system in these autoimmune muscle diseases, similar to its known role in lupus (SLE).","whyItMatters":"LL-37 is normally a protective antimicrobial peptide, but this study reveals its darker side: in autoimmune diseases, it may trigger harmful immune responses. The finding that LL-37 activates the same interferon pathway in myositis as it does in lupus suggests a common peptide-driven mechanism across multiple autoimmune diseases. The vitamin D connection is also notable, since vitamin D regulates LL-37 expression.","specificNumbers":"Muscle biopsies: 3 PM + 5 DM (short duration), 3 PM + 1 DM (long duration) · Skin biopsies: 5 DM symptomatic, 3 PM + 3 DM non-symptomatic · 6 SLE controls · 5 muscle + 6 skin healthy controls · All PM/DM patients: low vitamin D","methodology":"Case-control study comparing tissue biopsies from PM and DM patients with SLE patients and healthy controls. Muscle and skin biopsies were immunohistochemically stained for LL-37, neutrophils (CD66b), plasmacytoid dendritic cells (BDCA-2), MxA (interferon marker), and macrophages (CD68, CD163). Double staining confirmed LL-37 expression in neutrophils. Serum vitamin D (25(OH)D3) levels measured in 8 myositis patients and 40 healthy controls.","limitations":"Very small sample sizes (3-5 patients per group) limit statistical power and generalizability. Cross-sectional design cannot establish whether LL-37 elevation is a cause or consequence of the inflammatory process. The study cannot prove that LL-37 triggers myositis — only that it's present at higher levels and correlates with interferon markers."},{"rthcId":"RPEP-03380","title":"Perspectives on cardiovascular effects of incretin-based drugs: From bedside to bench, return trip.","authors":"Luconi, Michaela; Cantini, Giulia; Ceriello, Antonio; Mannucci, Edoardo","year":2017,"journal":"International journal of cardiology, 241, 302-310","doi":"10.1016/j.ijcard.2017.02.126","pmid":"28285800","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03381","title":"Cyclophosphamide induced stomach and duodenal lesions as a NO-system disturbance in rats: L-NAME, L-arginine, stable gastric pentadecapeptide BPC 157.","authors":"Luetic, Krešimir; Sucic, Mario; Vlainic, Josipa; Halle, Zeljka Belosic; Strinic, Dean; Vidovic, Tinka; Luetic, Franka; Marusic, Marinko; Gulic, Sasa; Pavelic, Tatjana Turudic; Kokot, Antonio; Seiwerth, Ranka Serventi; Drmic, Domagoj; Batelja, Lovorka; Seiwerth, Sven; Sikiric, Predrag","year":2017,"journal":"Inflammopharmacology, 25(2), 255-264","doi":"10.1007/s10787-017-0330-7","pmid":"28255738","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03382","title":"Migraine, Neurogenic Inflammation, Drug Development - Pharmacochemical Aspects.","authors":"Lukacs, Melinda; Tajti, Janos; Fulop, Ferenc; Toldi, Jozsef; Edvinsson, Lars; Vecsei, Laszlo","year":2017,"journal":"Current medicinal chemistry, 24(33), 3649-3665","doi":"10.2174/0929867324666170712163437","pmid":"28707585","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review assessed therapeutic strategies targeting neurogenic inflammation mediators in migraine:\n\n- CGRP pathway: Phase III clinical trials of monoclonal antibodies against CGRP and the CGRP receptor showed the most promise — these would later become approved drugs (erenumab, fremanezumab, galcanezumab)\n- Substance P: Preclinical and clinical studies targeting SP were all terminated with no significant benefit over placebo\n- Nitric oxide synthase (NOS): Clinical trials targeting NOS were similarly terminated without significant results\n- PACAP and PAC1 receptor: Identified as a promising new therapeutic target based on emerging evidence of PACAP's role in migraine\n- Kynurenic acid (KYNA) analogs: Highlighted as another novel approach worth pursuing","whyItMatters":"This review captures a pivotal moment in migraine pharmacology — the transition from failed neuropeptide-targeting strategies (substance P, nitric oxide) to the successful development of anti-CGRP therapies that would soon revolutionize migraine treatment. Understanding which neuropeptide targets succeeded and which failed informs the next generation of drug development, particularly for PACAP-targeted therapies that are now in clinical development.","specificNumbers":"","methodology":"The authors conducted a systematic literature search of PubMed for studies published through January 2017 on therapeutic strategies in migraine related to neurogenic inflammation. The review focused on substances and cytokines released during neurogenic inflammation, covering preclinical and clinical drug development across multiple neuropeptide and neurotransmitter targets.","limitations":"The literature search was limited to PubMed and studies published through January 2017, missing subsequent developments including the approval of anti-CGRP drugs (2018) and the advancement of PACAP-targeting therapies. The review primarily covers pharmacological approaches and may not fully address non-peptide targets or device-based treatments for migraine. As a review focused on neurogenic inflammation, it may underrepresent other migraine mechanisms like cortical spreading depression."},{"rthcId":"RPEP-03383","title":"Peptide-Drug Conjugate: A Novel Drug Design Approach.","authors":"Ma, Liang; Wang, Chao; He, Zihao; Cheng, Biao; Zheng, Ling; Huang, Kun","year":2017,"journal":"Current medicinal chemistry, 24(31), 3373-3396","doi":"10.2174/0929867324666170404142840","pmid":"28393694","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03384","title":"Fabrication of nanofibrous electrospun scaffolds from a heterogeneous library of co- and self-assembling peptides.","authors":"Maleki, Mahboubeh; Natalello, Antonino; Pugliese, Raffaele; Gelain, Fabrizio","year":2017,"journal":"Acta biomaterialia, 51, 268-278","doi":"10.1016/j.actbio.2017.01.038","pmid":"28093364","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03385","title":"Expression of Antimicrobial Peptides by Uveal and Cutaneous Melanoma Cells and Investigation of Their Role in Tumor Cell Migration and Vasculogenic Mimicry.","authors":"Manarang, Joseph C; Otteson, Deborah C; McDermott, Alison M","year":2017,"journal":"Current eye research, 42(11), 1474-1481","doi":"10.1080/02713683.2017.1339806","pmid":"28910167","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Melanoma cells expressed variable levels of antimicrobial peptide mRNA, with LL-37 (cathelicidin) generally increased and hBD-4 (β-defensin 4) decreased in most melanoma cell lines compared to primary uveal melanocytes. However, neither HNP-1 (α-defensin) nor LL-37 had an observable influence on tumor cell migration in scratch assays.\n\nAggressive cutaneous melanoma cells exhibited vasculogenic mimicry (forming blood vessel-like channels) in 3D culture, but AMP exposure did not alter this process. Overall, despite altered expression patterns, antimicrobial peptides had little influence on the major characteristics contributing to melanoma aggressiveness and progression.","whyItMatters":"There has been growing interest in repurposing antimicrobial peptides as cancer therapies or understanding their role in tumor biology. This study provides an important negative result: while AMPs are expressed by melanoma cells with altered patterns, they do not appear to drive key aggressive behaviors. This helps narrow the focus of AMP-cancer research and prevents wasted effort on approaches unlikely to yield therapeutic benefit in melanoma.","specificNumbers":"","methodology":"AMP mRNA expression (HNP-1, LL-37, hBD-1 through hBD-4) was measured by RT-PCR in human uveal and cutaneous melanoma cell lines, primary uveal melanocytes, and primary uveal melanoma cells. Cell migration was assessed using an in vitro scratch assay with custom Matlab analysis. Vasculogenic mimicry was evaluated in 3D cultures using light and fluorescence microscopy.","limitations":"This was an in vitro study limited to cell lines and primary cultures, which may not fully represent AMP behavior in the complex tumor microenvironment in vivo. Only mRNA expression was measured (not protein levels), and only two AMPs (HNP-1 and LL-37) were functionally tested for migration effects. The study examined limited aspects of tumor biology — other AMP roles such as immune modulation were not assessed."},{"rthcId":"RPEP-03386","title":"Thymosin α1 Interacts with Hyaluronic Acid Electrostatically by Its Terminal Sequence LKEKK.","authors":"Mandaliti, Walter; Nepravishta, Ridvan; Pica, Francesca; Vallebona, Paola Sinibaldi; Garaci, Enrico; Paci, Maurizio","year":2017,"journal":"Molecules (Basel, Switzerland), 22(11)","doi":"10.3390/molecules22111843","pmid":"29077041","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03387","title":"Leptin and ghrelin concentration in hyperthyroid cats before and after radioactive iodine therapy compared to euthyroid control cats.","authors":"Marsilio, Sina; Glanemann, Barbara; Martin, Lucile; Szladovits, Balazs; Neiger, Reto","year":2017,"journal":"Tierarztliche Praxis. Ausgabe K, Kleintiere/Heimtiere, 45(2), 95-101","doi":"10.15654/TPK-160333","pmid":"28205670","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03388","title":"Effect of band and knife castration of beef calves on welfare indicators of pain at three relevant industry ages: II. Chronic pain.","authors":"Marti, S; Meléndez, D M; Pajor, E A; Moya, D; Heuston, C E M; Gellatly, D; Janzen, E D; Schwartzkopf-Genswein, K S","year":2017,"journal":"Journal of animal science, 95(10), 4367-4380","doi":"10.2527/jas2017.1763","pmid":"29108039","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03389","title":"Neurochemical effects of photobiostimulation in the trigeminal ganglion after inferior alveolar nerve injury.","authors":"Martins, D O; Santos, F M; Britto, L R G; Lemos, J B D; Chacur, M","year":2017,"journal":"Journal of biological regulators and homeostatic agents, 31(1), 147-152","doi":null,"pmid":"28337884","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In rats with inferior alveolar nerve (IAN) injury:\n\n- Nerve injury alone increased expression of TRPV1 (pain receptor) and substance P in the trigeminal ganglion, but did not change GluA1, GluA2 (AMPA receptors), or CGRP expression\n- Low-level laser therapy (LLLT) produced multiple changes:\n  - Decreased TRPV1 expression (pain receptor)\n  - Decreased substance P expression (pain neuropeptide)\n  - Decreased CGRP expression (pain neuropeptide)\n  - Increased GluA1 and GluA2 expression (AMPA receptors)\n\nThe combined pattern suggests LLLT counteracts the molecular changes that drive pain sensitization after nerve injury.","whyItMatters":"Facial pain from nerve injury (trigeminal neuropathy) can be debilitating and difficult to treat with conventional medications. Understanding exactly how low-level laser therapy reduces pain at the molecular level — by decreasing CGRP and substance P — could help optimize LLLT protocols and validate it as a legitimate treatment option. It also highlights how neuropeptide modulation is central to pain management beyond traditional drug approaches.","specificNumbers":"","methodology":"Sprague-Dawley rats underwent inferior alveolar nerve injury surgery. Three groups were compared: naive (uninjured), injured without treatment, and injured with low-level laser therapy. Protein expression of GluA1, GluA2 (AMPA receptor subunits), CGRP, substance P, and TRPV1 was measured in trigeminal ganglion tissue and compared across groups.","limitations":"This is an animal study using rats, and results may not directly translate to human facial pain conditions. The specific LLLT parameters (wavelength, power, duration) are not detailed in the abstract. Sample sizes per group are not specified. The study measured protein expression but did not directly assess pain behavior. The mechanism linking LLLT to neuropeptide changes is not fully explained. The 2017 publication date means newer LLLT protocols may differ."},{"rthcId":"RPEP-03390","title":"Neurotrophins and Migraine.","authors":"Martins, L B; Teixeira, A L; Domingues, R B","year":2017,"journal":"Vitamins and hormones, 104, 459-473","doi":"10.1016/bs.vh.2016.10.003","pmid":"28215304","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03391","title":"Growth hormone releasing peptide-6 enhanced antibody titers against subunit antigens in mice (BALB/c), tilapia (Oreochromis niloticus) and African catfish (Clarias gariepinus).","authors":"Martínez, Rebeca; Hernández, Liz; Gil, Lázaro; Carpio, Yamila; Morales, Antonio; Herrera, Fidel; Rodríguez-Mallón, Alina; Leal, Yeny; Blanco, Aracelys; Estrada, Mario Pablo","year":2017,"journal":"Vaccine, 35(42), 5722-5728","doi":"10.1016/j.vaccine.2017.07.060","pmid":"28893476","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03392","title":"Involvement of substance P in the antinociceptive effect of botulinum toxin type A: Evidence from knockout mice.","authors":"Matak, Ivica; Tékus, Valéria; Bölcskei, Kata; Lacković, Zdravko; Helyes, Zsuzsanna","year":2017,"journal":"Neuroscience, 358, 137-145","doi":"10.1016/j.neuroscience.2017.06.040","pmid":"28673722","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03393","title":"Thymosin alpha 1 and HIV-1: recent advances and future perspectives.","authors":"Matteucci, Claudia; Grelli, Sandro; Balestrieri, Emanuela; Minutolo, Antonella; Argaw-Denboba, Ayele; Macchi, Beatrice; Sinibaldi-Vallebona, Paola; Perno, Carlo Federico; Mastino, Antonio; Garaci, Enrico","year":2017,"journal":"Future microbiology, 12, 141-155","doi":"10.2217/fmb-2016-0125","pmid":"28106477","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03394","title":"Resistant starch lowers postprandial glucose and leptin in overweight adults consuming a moderate-to-high-fat diet: a randomized-controlled trial.","authors":"Maziarz, Mindy Patterson; Preisendanz, Sara; Juma, Shanil; Imrhan, Victorine; Prasad, Chandan; Vijayagopal, Parakat","year":2017,"journal":"Nutrition journal, 16(1), 14","doi":"10.1186/s12937-017-0235-8","pmid":"28222742","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03395","title":"Semax, an analog of ACTH(4-7), regulates expression of immune response genes during ischemic brain injury in rats.","authors":"Medvedeva, Ekaterina V; Dmitrieva, Veronika G; Limborska, Svetlana A; Myasoedov, Nikolay F; Dergunova, Lyudmila V","year":2017,"journal":"Molecular genetics and genomics : MGG, 292(3), 635-653","doi":"10.1007/s00438-017-1297-1","pmid":"28255762","tags":[],"studyType":"animal-study","evidenceStrength":"low-moderate","keyFinding":"The synthetic peptide Semax — composed of the ACTH(4-7) fragment plus the tripeptide Pro-Gly-Pro (PGP) — protects rat brains during ischemic stroke primarily through immune system modulation. Genome-wide transcriptome analysis of the cerebral cortex revealed that Semax's most significant effect was on immune response genes.\n\nSpecifically, Semax enhanced antigen presentation pathways, intensified interferon signaling already activated by ischemia, affected immunoglobulin synthesis, and significantly increased expression of immunoglobulin heavy chain genes. It also strongly affected cytokine, stress response, and ribosomal protein genes after stroke.\n\nInterestingly, the PGP tripeptide component alone had the opposite effect — it suppressed immune activity and neurotransmission in the central nervous system. This suggests the two components of Semax may have distinct and potentially complementary roles in neuroprotection.","whyItMatters":"Stroke kills millions annually, and effective neuroprotective treatments remain limited. This study provides the first genome-wide view of how Semax protects the brain during stroke, revealing that its mechanism involves neuroimmune crosstalk — the communication between the nervous and immune systems. Understanding this mechanism could lead to better-designed peptide therapies for stroke and help explain why Semax has shown neuroprotective effects in clinical use in Russia.","specificNumbers":"Genome-wide biochip analysis · Focal cerebral ischemia model · Key pathways: antigen presentation, interferon signaling, immunoglobulin synthesis · PGP: suppressed immune activity + neurotransmission","methodology":"Rats with focal cerebral ischemia (middle cerebral artery occlusion) were treated with Semax or PGP. Researchers performed genome-wide transcriptome analysis of the cerebral cortex using biochip arrays, identified differentially expressed genes (DEGs), and used the bioinformatic tool Ingenuity iReport to map DEGs to biological processes and signaling pathways.","limitations":"This is an animal study in rats — results may not directly translate to human stroke patients. The study examines gene expression changes (transcriptome), not protein levels or functional outcomes, so the actual protective effect cannot be directly measured from this data alone. The specific mechanisms by which immune modulation leads to neuroprotection remain unclear. Semax is used clinically in Russia but lacks FDA approval and large-scale clinical trial data in Western countries."},{"rthcId":"RPEP-03396","title":"Hypermagnesemia disturbances in rats, NO-related: pentadecapeptide BPC 157 abrogates, L-NAME and L-arginine worsen.","authors":"Medvidovic-Grubisic, Maria; Stambolija, Vasilije; Kolenc, Danijela; Katancic, Jadranka; Murselovic, Tamara; Plestina-Borjan, Ivna; Strbe, Sanja; Drmic, Domagoj; Barisic, Ivan; Sindic, Aleksandra; Seiwerth, Sven; Sikiric, Predrag","year":2017,"journal":"Inflammopharmacology, 25(4), 439-449","doi":"10.1007/s10787-017-0323-6","pmid":"28210905","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In rats given toxic magnesium sulfate (560 mg/kg IP):\n\n- **BPC 157 (10 μg or 10 ng/kg)** given 15 minutes before magnesium completely abrogated hypermagnesemia, muscle weakness, muscle and brain lesions, elevated serum enzymes, and hyperkalaemia.\n- **L-NAME (NOS blocker)** and **L-arginine (NOS substrate)** each worsened all magnesium-induced disturbances when given alone.\n- **L-NAME + L-arginine together** paradoxically normalized all values.\n- **BPC 157** counteracted the aggravated toxicity caused by either L-NAME or L-arginine in combination with magnesium.\n- In HEK293 cells, increasing magnesium from 1 to 5 mM depolarized cells by 1.75 ± 0.44 mV; BPC 157 (1 μM) inhibited this depolarization in vitro.","whyItMatters":"Magnesium overdose is a medical emergency with limited treatment options (currently calcium gluconate and supportive care). BPC 157's ability to completely reverse magnesium toxicity at very low doses, working through the nitric oxide system, suggests a novel therapeutic mechanism. The peptide's consistent protective effects across a wide range of injury models make it one of the most studied cytoprotective peptides in preclinical research.","specificNumbers":"","methodology":"Wistar rats received magnesium sulfate (560 mg/kg IP) with or without pretreatment (15 min prior) with BPC 157 (10 μg or 10 ng/kg IP), L-NAME (5 mg/kg IP), L-arginine (100 mg/kg IP), or combinations. Muscle weakness was scored, and serum magnesium, potassium, and enzyme levels were measured during and after a 30-minute observation period. Muscle and brain histopathology was assessed. Cell depolarization experiments used HEK293 cells exposed to increasing magnesium concentrations ± BPC 157.","limitations":"All data are from rats and cell culture — no human studies exist for BPC 157 in any indication. BPC 157 was given as pretreatment (before magnesium), so its efficacy as a rescue therapy after toxicity onset is unknown. The study comes from the Sikiric lab group, which has published the majority of BPC 157 research; independent replication by other groups is limited. The exact molecular target of BPC 157 remains unidentified."},{"rthcId":"RPEP-03397","title":"Calcitonin gene-related peptide monoclonal antibodies for migraine prevention: comparisons across randomized controlled studies.","authors":"Mitsikostas, Dimos D; Reuter, Uwe","year":2017,"journal":"Current opinion in neurology, 30(3), 272-280","doi":"10.1097/WCO.0000000000000438","pmid":"28240610","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In high-frequency episodic migraine, the reduction in monthly migraine days from baseline versus placebo at end of treatment was:\n- Eptinezumab (ALD403): -1.0 days (weeks 5-8)\n- Erenumab (AMG334): -1.1 days (weeks 9-12)\n- Galcanezumab (LY2951742): -1.2 days (weeks 9-12)\n- Fremanezumab (TEV48125, 225 mg): -2.6 days (weeks 9-12)\n\nNumbers needed to treat (NNT) for responders were 4.7, 6.2, 4.0, and 4.0 respectively — all clinically meaningful. The odds ratios for any adverse event were remarkably close to 1.0 (1.09, 0.96, 1.07, 1.05), indicating that side effects were essentially no different from placebo. The authors noted that overall efficacy was comparable to existing oral preventive migraine medications, but the safety and tolerability advantages were the key differentiator.","whyItMatters":"This review captured a pivotal moment in headache medicine — when the first disease-specific preventive migraine treatments were emerging. Previous preventive medications (beta-blockers, antidepressants, antiepileptics) were all repurposed from other conditions and came with significant side effects. CGRP antibodies represented the first treatments designed specifically for migraine based on understanding the underlying peptide biology, fundamentally changing how the condition is managed.","specificNumbers":"","methodology":"Comparative review of published phase 2 randomized controlled trials for all four CGRP-targeting monoclonal antibodies in episodic and chronic migraine prevention. The authors standardized comparisons across trials by examining change from baseline in migraine days, number needed to treat, and odds ratios for adverse events.","limitations":"This review was based on phase 2 trial data only — smaller and shorter than the subsequent phase 3 trials. Cross-trial comparisons are inherently limited because the studies had different designs, patient populations, and endpoints. Long-term safety data was not available at the time. The review noted that pregnancy safety, cardiovascular effects, and cost-effectiveness required further evaluation — questions that have since been partially addressed."},{"rthcId":"RPEP-03398","title":"Substance P effects exclusively on prototypic neurons in mouse globus pallidus.","authors":"Mizutani, Kazuko; Takahashi, Susumu; Okamoto, Shinichiro; Karube, Fuyuki; Fujiyama, Fumino","year":2017,"journal":"Brain structure & function, 222(9), 4089-4110","doi":"10.1007/s00429-017-1453-8","pmid":"28608288","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03399","title":"Amylin Enhances Amyloid-β Peptide Brain to Blood Efflux Across the Blood-Brain Barrier.","authors":"Mohamed, Loqman A; Zhu, Haihao; Mousa, Youssef M; Wang, Erming; Qiu, Wei Qiao; Kaddoumi, Amal","year":2017,"journal":"Journal of Alzheimer's disease : JAD, 56(3), 1087-1099","doi":"10.3233/JAD-160800","pmid":"28059785","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A single intraperitoneal injection of amylin in Tg2576 Alzheimer's mice significantly increased amyloid-beta (Aβ) serum levels, indicating enhanced brain-to-blood clearance. This effect was abolished by AC253 (an amylin receptor antagonist), confirming receptor dependence.\n\nMechanistic studies using a blood-brain barrier (BBB) cell model showed:\n- Amylin enhanced Aβ transport across the BBB\n- Two amylin antagonists and siRNA knockdown of the Ramp3 receptor component all blocked this effect\n- Amylin treatment induced LRP1 (a major Aβ efflux receptor) translocation from intracellular pools to the plasma membrane\n- This LRP1 membrane enrichment explains the enhanced Aβ uptake and transport\n\nThe complete mechanism: amylin → amylin receptor activation → LRP1 subcellular translocation to BBB endothelial membrane → enhanced Aβ brain-to-blood clearance.","whyItMatters":"Impaired amyloid-beta clearance from the brain is a key driver of Alzheimer's disease — the brain produces amyloid normally but can't remove it fast enough, causing toxic buildup. Finding ways to enhance clearance is a major therapeutic strategy. This study shows amylin — an already well-characterized peptide with an FDA-approved analog (pramlintide) — can accelerate this clearance through a specific, druggable mechanism. Understanding exactly how amylin enhances Aβ clearance (via LRP1 translocation) opens the door to designing optimized treatments.","specificNumbers":"","methodology":"Researchers used Tg2576 Alzheimer's model mice and administered single intraperitoneal amylin injections, measuring serum Aβ levels to assess brain-to-blood clearance. The amylin receptor antagonist AC253 was used to confirm receptor dependence. In vitro mechanistic studies used a cell-based BBB model to measure Aβ transport, with two amylin antagonists and siRNA knockdown of Ramp3 to confirm receptor involvement. Western blotting of membrane fractions assessed LRP1 subcellular localization after amylin treatment.","limitations":"This is a preclinical study in transgenic mice that overexpress amyloid precursor protein, which may not fully model human Alzheimer's. The study measured acute effects of a single amylin injection; chronic treatment effects and long-term safety were not assessed. The BBB cell model is simplified compared to the in vivo blood-brain barrier. While the mechanism is elegantly demonstrated, translation to humans requires confirmation that amylin can achieve similar LRP1 effects at the human BBB. The paradox of amylin's own aggregation potential in the brain was not addressed."},{"rthcId":"RPEP-03400","title":"Safety issues with glucagon-like peptide-1 receptor agonists (pancreatitis, pancreatic cancer and cholelithiasis): Data from randomized controlled trials.","authors":"Monami, Matteo; Nreu, Besmir; Scatena, Alessia; Cresci, Barbara; Andreozzi, Francesco; Sesti, Giorgio; Mannucci, Edoardo","year":2017,"journal":"Diabetes, obesity & metabolism, 19(9), 1233-1241","doi":"10.1111/dom.12926","pmid":"28244632","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03401","title":"Evaluation of molecules or extracts modulating seborrhea and its consequences, using normal human culture of sebocytes and keratinocytes, skin explants models and in vivo methods: a case study.","authors":"Mondon, Philippe; Toso, Roberto Dal; Ringenbach, Caroline; LavaissiÈre, Laurent; Doridot, Emmanuel; Ouvrat, Émilie; Brahimi, Sandra","year":2017,"journal":"Journal of cosmetic science, 68(2), 183-194","doi":null,"pmid":"29619942","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03402","title":"Entry of a Six-Residue Antimicrobial Peptide Derived from Lactoferricin B into Single Vesicles and Escherichia coli Cells without Damaging their Membranes.","authors":"Moniruzzaman, Md; Islam, Md Zahidul; Sharmin, Sabrina; Dohra, Hideo; Yamazaki, Masahito","year":2017,"journal":"Biochemistry, 56(33), 4419-4431","doi":"10.1021/acs.biochem.6b01274","pmid":"28752991","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"LfcinB (4-9), with the sequence RRWQWR, entered E. coli cytoplasm without inducing membrane leakage. This was demonstrated by two independent methods: (1) SYTOX green exclusion showed no membrane damage, and (2) fluorescently labeled peptide entered cells without leakage of the cytoplasmic marker calcein.\n\nThe same behavior was observed in artificial membrane vesicles (GUVs) — the labeled peptide translocated across the lipid bilayer without leakage of the encapsulated probe AF647. Interaction with DNA significantly increased the peptide's fluorescence intensity, suggesting intracellular DNA binding as a potential antimicrobial mechanism.","whyItMatters":"Understanding how antimicrobial peptides actually kill bacteria is essential for designing better peptide antibiotics. If small peptides can enter bacteria without membrane disruption, it means they work through intracellular targets like DNA — a completely different mechanism than membrane lysis. This opens new strategies for designing peptide antibiotics that might be effective even against bacteria that can reinforce their membranes.","specificNumbers":"","methodology":"Fluorescently labeled LfcinB (4-9) (Rh-LfcinB) was studied using confocal microscopy in two systems: (1) live E. coli cells pre-loaded with calcein as a leakage marker, and (2) giant unilamellar vesicles (GUVs) made from bacterial-like lipids (DOPG/DOPC) containing the fluorescent probe AF647. SYTOX green assays monitored membrane integrity. DNA-peptide interactions were assessed by fluorescence changes upon binding.","limitations":"The study was conducted entirely in vitro using a single bacterial species (E. coli) and artificial membrane vesicles. The exact intracellular target and killing mechanism were not definitively established — DNA binding was demonstrated but its role in cell death was not confirmed. The peptide concentrations used may not reflect physiologically achievable levels. Only one peptide fragment was studied."},{"rthcId":"RPEP-03403","title":"Antioxidant, ACE-inhibitory and antimicrobial activity of fermented goat milk: activity and physicochemical property relationship of the peptide components.","authors":"Moreno-Montoro, Miriam; Olalla-Herrera, Manuel; Rufián-Henares, José Ángel; Martínez, Rafael Giménez; Miralles, Beatriz; Bergillos, Triana; Navarro-Alarcón, Miguel; Jauregi, Paula","year":2017,"journal":"Food & function, 8(8), 2783-2791","doi":"10.1039/c7fo00666g","pmid":"28702643","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03404","title":"Efficacy of aprepitant for CHOP chemotherapy-induced nausea, vomiting, and anorexia.","authors":"Morita, Mihoko; Kishi, Shinji; Ookura, Miyuki; Matsuda, Yasufumi; Tai, Katsunori; Yamauchi, Takahiro; Ueda, Takanori","year":2017,"journal":"Current problems in cancer, 41(6), 419-425","doi":"10.1016/j.currproblcancer.2017.09.001","pmid":"29061362","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03405","title":"Future Treatment of Constipation-associated Disorders: Role of Relamorelin and Other Ghrelin Receptor Agonists.","authors":"Mosińska, Paula; Zatorski, Hubert; Storr, Martin; Fichna, Jakub","year":2017,"journal":"Journal of neurogastroenterology and motility, 23(2), 171-179","doi":"10.5056/jnm16183","pmid":"28238253","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03406","title":"The first identified cathelicidin from tree frogs possesses anti-inflammatory and partial LPS neutralization activities.","authors":"Mu, Lixian; Zhou, Lei; Yang, Juanjuan; Zhuang, Li; Tang, Jing; Liu, Tong; Wu, Jing; Yang, Hailong","year":2017,"journal":"Amino acids, 49(9), 1571-1585","doi":"10.1007/s00726-017-2449-7","pmid":"28593346","tags":["antimicrobial-peptides","inflammation-immunology"],"studyType":"in-vitro-study","evidenceStrength":"preliminary","keyFinding":"Cathelicidin-PP is a 32-residue peptide (ASENGKCNLLCLVKKKLRAVGNVIKTVVGKIA) that adopts a β-sheet structure in membrane-mimetic environments. It demonstrated potent antimicrobial activity against bacteria and fungi, with particular effectiveness against Gram-negative bacteria. Scanning electron microscopy confirmed it kills bacteria by disrupting membrane integrity.\n\nBeyond direct antimicrobial action, cathelicidin-PP significantly inhibited LPS-stimulated production of nitric oxide, TNF-α, IL-1β, and IL-6 in macrophages. This anti-inflammatory effect involved both MAPK (ERK, JNK, and p38) and NF-κB signaling pathways. The peptide also partially neutralized LPS in a dose-dependent manner. In live tree frogs, bacterial infection caused increased cathelicidin-PP expression in immune-related tissues, confirming its role in natural host defense.","whyItMatters":"With antibiotic resistance rising globally, finding new antimicrobial compounds is urgent. Cathelicidins are especially interesting because they combine direct germ-killing with immune regulation — they fight infection on two fronts simultaneously. This discovery expands the known diversity of cathelicidins into tree frogs, a massive and largely untapped reservoir of potential drug leads. The fact that cathelicidin-PP has low toxicity to mammalian cells while retaining both antimicrobial and anti-inflammatory activity makes it a promising template for new drug development.","specificNumbers":"32 amino acids; β-sheet structure; inhibits TNF-α, IL-1β, IL-6, NO; MAPK (ERK, JNK, p38) and NF-κB pathways; dose-dependent LPS neutralization; low cytotoxicity","methodology":"Researchers purified cathelicidin-PP from Polypedates puerensis tree frog skin and determined its amino acid sequence. They used circular dichroism spectroscopy to analyze its structure, antimicrobial assays to test its germ-killing ability, and scanning electron microscopy to visualize how it destroys bacterial membranes. Anti-inflammatory properties were tested in LPS-stimulated mouse peritoneal macrophages by measuring cytokines and nitric oxide. LPS neutralization was assessed in dose-response assays. Finally, qPCR was used to measure cathelicidin-PP expression in frog tissues after bacterial infection.","limitations":"All experiments were conducted in vitro or ex vivo — there were no animal infection models testing whether cathelicidin-PP protects against disease in a living organism. The peptide was tested against a limited panel of microorganisms. No pharmacokinetic data (how long it lasts in the body) or toxicity studies in whole animals were performed. The clinical translatability of a frog-derived peptide to human medicine is unknown."},{"rthcId":"RPEP-03407","title":"Cellular Sites and Mechanisms Linking Reduction of Dipeptidyl Peptidase-4 Activity to Control of Incretin Hormone Action and Glucose Homeostasis.","authors":"Mulvihill, Erin E; Varin, Elodie M; Gladanac, Bojana; Campbell, Jonathan E; Ussher, John R; Baggio, Laurie L; Yusta, Bernardo; Ayala, Jennifer; Burmeister, Melissa A; Matthews, Dianne; Bang, K W Annie; Ayala, Julio E; Drucker, Daniel J","year":2017,"journal":"Cell metabolism, 25(1), 152-165","doi":"10.1016/j.cmet.2016.10.007","pmid":"27839908","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03408","title":"TLN-58, an Additional hCAP18 Processing Form, Found in the Lesion Vesicle of Palmoplantar Pustulosis in the Skin.","authors":"Murakami, Masamoto; Kameda, Kenji; Tsumoto, Hiroki; Tsuda, Teruko; Masuda, Kana; Utsunomiya, Ryo; Mori, Hideki; Miura, Yuri; Sayama, Koji","year":2017,"journal":"The Journal of investigative dermatology, 137(2), 322-331","doi":"10.1016/j.jid.2016.07.044","pmid":"27771329","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03409","title":"Constitutive activity of the Ghrelin receptor reduces surface expression of voltage-gated Ca2+ channels in a CaVβ-dependent manner.","authors":"Mustafá, Emilio R; López Soto, Eduardo J; Martínez Damonte, Valentina; Rodríguez, Silvia S; Lipscombe, Diane; Raingo, Jesica","year":2017,"journal":"Journal of cell science, 130(22), 3907-3917","doi":"10.1242/jcs.207886","pmid":"29038230","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GHSR (growth hormone secretagogue receptor type 1a) constitutively — without agonist binding — inhibits the forward trafficking of multiple CaV channel subtypes, reducing their surface expression. This effect depends on the presence of CaVβ subunits, which normally help CaVα1 subunits leave the endoplasmic reticulum for the cell surface. GHSR's constitutive activity traps calcium channels intracellularly, suggesting a tonic suppressive effect on calcium signaling in brain regions expressing both GHSR and these calcium channels.","whyItMatters":"Most research on ghrelin focuses on its role as a hunger hormone. This study reveals that the ghrelin receptor has an always-on function that shapes neuronal calcium signaling independent of ghrelin levels. This could fundamentally change how we understand the ghrelin system's role in the brain — it's not just about when ghrelin is released, but about a constant baseline effect on neuronal excitability in circuits controlling appetite, reward, and learning.","specificNumbers":"","methodology":"Researchers used cell line models to study the interaction between GHSR and various CaV channel subtypes. They measured calcium channel surface expression in the presence and absence of GHSR, tested the requirement for CaVβ subunits, and examined the ER-to-surface trafficking pathway. Experiments were conducted without ghrelin agonist to isolate the constitutive (ligand-independent) activity of the receptor.","limitations":"The study was conducted in cell lines rather than intact neurons or brain tissue, which may not fully replicate the complexity of neuronal signaling. The specific CaV subtypes affected and the magnitude of the effect in native neurons in vivo are not established. The study does not demonstrate functional consequences on neuronal firing or behavior."},{"rthcId":"RPEP-03410","title":"Immunolocalization of Substance P and NK-1 Receptor in ADIPOSE Stem Cells.","authors":"Muñoz, Miguel; Muñoz, Mario F; Ayala, Antonio","year":2017,"journal":"Journal of cellular biochemistry, 118(12), 4686-4696","doi":"10.1002/jcb.26134","pmid":"28500728","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"For the first time, researchers demonstrated the presence and localization of Substance P (SP) and its receptor NK-1R in both human and rat adipose-derived stem cells (ADSCs). Using immunofluorescence, they showed that SP and NK1R are present in both the cytoplasm and nucleus of ADSCs, with NK1R levels being higher in the nucleus. Western blot analysis revealed different NK1R isoforms with distinct subcellular locations. Critically, SP was shown to induce proliferation and mitogenesis in ADSCs through the NK1R pathway.","whyItMatters":"Adipose stem cells are widely used in regenerative medicine and tissue engineering. Discovering that Substance P and its receptor are present and functionally active in these cells opens new avenues for understanding how neuropeptides regulate stem cell behavior, potentially leading to better methods for controlling stem cell growth and differentiation in therapeutic applications.","specificNumbers":"NK1R higher in nucleus than cytoplasm · multiple NK1R isoforms identified · SP induces proliferation via NK1R · human and rat ADSCs tested","methodology":"Laboratory study using human and rat adipose-derived stem cells. Researchers used immunofluorescence microscopy to visualize the location of Substance P and NK-1 receptor within the cells, and Western blot analysis to identify different receptor isoforms and their subcellular distribution. Proliferation and mitogenesis assays were used to test functional effects of SP on ADSCs.","limitations":"This is a laboratory study using cells in culture, so the findings may not directly translate to how Substance P affects adipose stem cells in a living organism. The abstract does not provide quantitative data on proliferation rates or statistical significance of the mitogenesis findings. The study used a relatively basic set of techniques without exploring downstream signaling pathways in depth."},{"rthcId":"RPEP-03411","title":"Increased nuclear localization of substance P in human gastric tumor cells.","authors":"Muñoz, Miguel; Rosso, Marisa; Carranza, Andrés; Coveñas, Rafael","year":2017,"journal":"Acta histochemica, 119(3), 337-342","doi":"10.1016/j.acthis.2017.03.003","pmid":"28325510","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03412","title":"Cardioprotective effects of curcumin-loaded magnetic hydrogel nanocomposite (nanocurcumin) against doxorubicin-induced cardiac toxicity in rat cardiomyocyte cell lines.","authors":"Namdari, Mehrdad; Eatemadi, Ali","year":2017,"journal":"Artificial cells, nanomedicine, and biotechnology, 45(4), 731-739","doi":"10.1080/21691401.2016.1261033","pmid":"27924631","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03413","title":"Assessment of Pancreas Safety in the Development Program of Once-Weekly GLP-1 Receptor Agonist Dulaglutide.","authors":"Nauck, Michael A; Frossard, Jean-Louis; Barkin, Jamie S; Anglin, Greg; Hensley, Ingrid E; Harper, Kristine D; Milicevic, Zvonko","year":2017,"journal":"Diabetes care, 40(5), 647-654","doi":"10.2337/dc16-0984","pmid":"28283565","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03414","title":"HLA class I-restricted MYD88 L265P-derived peptides as specific targets for lymphoma immunotherapy.","authors":"Nelde, Annika; Walz, Juliane Sarah; Kowalewski, Daniel Johannes; Schuster, Heiko; Wolz, Olaf-Oliver; Peper, Janet Kerstin; Cardona Gloria, Yamel; Langerak, Anton W; Muggen, Alice F; Claus, Rainer; Bonzheim, Irina; Fend, Falko; Salih, Helmut Rainer; Kanz, Lothar; Rammensee, Hans-Georg; Stevanović, Stefan; Weber, Alexander N R","year":2017,"journal":"Oncoimmunology, 6(3), e1219825","doi":"10.1080/2162402X.2016.1219825","pmid":"28405493","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03415","title":"Milk Proteins Are Predigested Within the Human Mammary Gland.","authors":"Nielsen, Søren D; Beverly, Robert L; Dallas, David C","year":2017,"journal":"Journal of mammary gland biology and neoplasia, 22(4), 251-261","doi":"10.1007/s10911-018-9388-0","pmid":"29464498","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"More than 1,100 unique peptides derived from milk protein hydrolysis were identified within the mammary gland — produced before the milk was ever expressed. These peptides originated from 42 different milk proteins. Among them, 306 peptides were predicted to have bioactive properties.\n\nPlasmin was predicted to be the primary protease responsible for the in-gland protein hydrolysis. The study's careful methodology — collecting milk directly into antiprotease cocktails on ice with immediate freezing — ensured these peptides were genuinely produced within the mammary gland rather than during sample handling.","whyItMatters":"This study fundamentally changes our understanding of breastfeeding biology. The mammary gland is not just a milk factory — it's an active digestive and bioactive peptide production system. These pre-formed peptides may give breastfed infants immediate access to antimicrobial, immunomodulatory, and other beneficial peptides without waiting for the baby's immature digestive system to break down proteins. This could help explain some of the well-documented health benefits of breastfeeding over formula feeding.","specificNumbers":"","methodology":"Four lactating mothers expressed breast milk directly into a mixture of protease inhibitors on ice, followed by immediate freezing to halt any post-expression enzymatic activity. This ensured only peptides produced inside the mammary gland were captured. Samples were analyzed using mass spectrometry to identify the full peptide profile. Multiple computational approaches were used to predict which proteases generated the peptides and which peptides had potential biological activities.","limitations":"The study included only 4 mothers, which limits the ability to assess individual variation in mammary gland peptide production. The bioactivity predictions were computational and need experimental validation — predicted bioactivity doesn't guarantee actual biological function. The study could not determine the quantities of each peptide present, only their identity. It's difficult to completely rule out some minimal protease activity despite the antiprotease cocktail protocol."},{"rthcId":"RPEP-03416","title":"Milk bioactive peptide database: A comprehensive database of milk protein-derived bioactive peptides and novel visualization.","authors":"Nielsen, Søren Drud; Beverly, Robert L; Qu, Yunyao; Dallas, David C","year":2017,"journal":"Food chemistry, 232, 673-682","doi":"10.1016/j.foodchem.2017.04.056","pmid":"28490127","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03417","title":"Friends or Foes? Host defense (antimicrobial) peptides and proteins in human skin diseases.","authors":"Niyonsaba, François; Kiatsurayanon, Chanisa; Chieosilapatham, Panjit; Ogawa, Hideoki","year":2017,"journal":"Experimental dermatology, 26(11), 989-998","doi":"10.1111/exd.13314","pmid":"28191680","tags":["antimicrobial-peptides","dermatology"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Antimicrobial peptides (AMPs) in the skin are a double-edged sword. On one hand, they protect against infections by killing bacteria, viruses, fungi, and parasites. They also promote wound healing, stimulate cell growth and migration, and strengthen the skin barrier. On the other hand, these same peptides actively contribute to the development and progression of several skin diseases.\n\nThe review identifies specific roles in multiple conditions: AMPs drive inflammatory processes in psoriasis, contribute to the altered immune response in atopic dermatitis (eczema), play a role in the redness and inflammation of rosacea, and are involved in acne, lupus, and systemic sclerosis. The key AMPs discussed include defensins, cathelicidins (like LL-37), S100 proteins, ribonucleases, and dermcidin.","whyItMatters":"This review reframes how we think about the skin's natural defense peptides. For decades, AMPs were seen purely as protective — the body's built-in antibiotics. This paper consolidates evidence that they can also be part of the problem in inflammatory skin diseases. This dual nature has major therapeutic implications: treatments that boost AMPs might help fight infections but could worsen conditions like psoriasis or rosacea, and vice versa.","specificNumbers":"5 major AMP families reviewed (defensins, cathelicidins, S100 proteins, ribonucleases, dermcidin) · 6 skin diseases discussed (psoriasis, atopic dermatitis, rosacea, acne, lupus, systemic sclerosis)","methodology":"This is a narrative review published in Experimental Dermatology that synthesizes published research on the roles of antimicrobial peptides and proteins in skin biology and skin diseases. The authors reviewed literature on five major families of skin-derived AMPs and their involvement in both protective immunity and disease pathogenesis.","limitations":"As a narrative review, this paper summarizes and interprets existing research rather than generating new data. The dual roles of AMPs are described qualitatively; the review does not quantify the balance between protective and pathogenic effects. The relative contribution of AMPs to each skin disease compared to other pathogenic factors is not precisely delineated."},{"rthcId":"RPEP-03418","title":"Antimicrobial Peptides: A Promising Therapeutic Strategy in Tackling Antimicrobial Resistance.","authors":"Nuti, Ramya; Goud, Nerella S; Saraswati, A Prasanth; Alvala, Ravi; Alvala, Mallika","year":2017,"journal":"Current medicinal chemistry, 24(38), 4303-4314","doi":"10.2174/0929867324666170815102441","pmid":"28814242","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03419","title":"Timeline of changes in appetite during weight loss with a ketogenic diet.","authors":"Nymo, S; Coutinho, S R; Jørgensen, J; Rehfeld, J F; Truby, H; Kulseng, B; Martins, C","year":2017,"journal":"International journal of obesity (2005), 41(8), 1224-1231","doi":"10.1038/ijo.2017.96","pmid":"28439092","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03420","title":"Peripheral Interaction of Resolvin D1 and E1 with Opioid Receptor Antagonists for Antinociception in Inflammatory Pain in Rats.","authors":"Oehler, Beatrice; Mohammadi, Milad; Perpina Viciano, Cristina; Hackel, Dagmar; Hoffmann, Carsten; Brack, Alexander; Rittner, Heike L","year":2017,"journal":"Frontiers in molecular neuroscience, 10, 242","doi":"10.3389/fnmol.2017.00242","pmid":"28824373","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Resolvin D1 (RvD1) and chemerin (a ChemR23 ligand) both reduced inflammatory pain in early and late phases of CFA-induced hindpaw inflammation in rats. However, this pain relief was completely prevented by peripheral blockade of the μ-opioid receptor using low-dose local naloxone, or by local injection of antibodies against β-endorphin and met-enkephalin.\n\nImportantly, RvD1 did not directly activate opioid receptors — it did not stimulate G-protein-coupled MOR signaling or β-arrestin recruitment. It also did not stimulate the release of β-endorphin from macrophages or neutrophils. The interaction appears to involve TRPA1 channels: naloxone blocked the antinociceptive effects of the TRPA1 inhibitor HC-030031 both in vivo and in vitro (calcium influx in dorsal root ganglion neurons). Peripheral naloxone alone lowered mechanical pain thresholds, indicating that endogenous opioid tone is necessary for the normal balance of pain signaling.","whyItMatters":"Understanding how the body's natural pain control systems interact is crucial for developing better pain treatments that work with the body rather than against it. The finding that resolvins require endogenous opioid peptide signaling to work suggests these pathways should be considered as an integrated network, not isolated targets. This has implications for patients taking opioid antagonists (like naltrexone) who might have reduced benefit from anti-inflammatory approaches.","specificNumbers":"","methodology":"Researchers used CFA (complete Freund's adjuvant)-induced hindpaw inflammation in male Wistar rats to model inflammatory pain. RvD1 and chemerin were administered locally, and pain relief was assessed using mechanical nociceptive thresholds. Opioid receptor involvement was tested using local naloxone and anti-opioid peptide antibodies. In vitro experiments used dorsal root ganglion neurons to assess TRPA1-mediated calcium influx. G-protein activation and β-arrestin recruitment assays tested whether RvD1 directly activates opioid receptors.","limitations":"The study was conducted in rats, and pain pathways differ between rodents and humans. Only male rats were used, so sex differences in pain modulation were not examined. The exact mechanism linking resolvins, TRPA1, and opioid receptors remains unclear — the study demonstrated the interaction but could not fully explain the molecular basis. The CFA model produces robust inflammation that may not represent all types of chronic pain."},{"rthcId":"RPEP-03421","title":"Mapping of KNDy neurons and immunohistochemical analysis of the interaction between KNDy and substance P neural systems in goat.","authors":"Okamura, Hiroaki; Yamamura, Takashi; Wakabayashi, Yoshihiro","year":2017,"journal":"The Journal of reproduction and development, 63(6), 571-580","doi":"10.1262/jrd.2017-103","pmid":"29109352","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03422","title":"Immunolocalization of substance P and NK-1 receptor in vascular anomalies.","authors":"Ortiz-Prieto, Alejandro; Bernabeu-Wittel, José; Zulueta-Dorado, Teresa; Lorente-Lavirgen, Ana I; Muñoz, Miguel","year":2017,"journal":"Archives of dermatological research, 309(2), 97-102","doi":"10.1007/s00403-016-1707-y","pmid":"27988892","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03423","title":"Design and Evolution of a Macrocyclic Peptide Inhibitor of the Sonic Hedgehog/Patched Interaction.","authors":"Owens, Andrew E; de Paola, Ivan; Hansen, William A; Liu, Yi-Wen; Khare, Sagar D; Fasan, Rudi","year":2017,"journal":"Journal of the American Chemical Society, 139(36), 12559-12568","doi":"10.1021/jacs.7b06087","pmid":"28759213","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03424","title":"Topical peptides as cosmeceuticals.","authors":"Pai, Varadraj Vasant; Bhandari, Prasana; Shukla, Pankaj","year":2017,"journal":"Indian journal of dermatology, venereology and leprology, 83(1), 9-18","doi":"10.4103/0378-6323.186500","pmid":"27451932","tags":["cosmetic-peptides","skincare"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Cosmeceutical peptides fall into four functional categories — signal peptides that stimulate extracellular matrix production (especially collagen), structural peptides that stabilize skin architecture, carrier peptides that deliver trace elements like copper to cells, and neurotransmitter-inhibiting peptides that reduce muscle contraction to minimize wrinkles.\n\nThe review notes that while peptides offer advantages including selectivity, low immunogenicity, and involvement in multiple skin functions, their clinical evidence for efficacy is often weak. Absorption through skin remains a challenge due to low lipophilicity and high molecular weight, though penetration enhancers, chemical modification, and encapsulation can improve delivery.","whyItMatters":"Peptide-based skincare has become a massive consumer market, but the scientific basis varies widely by product. This review provides a framework for understanding which categories of cosmeceutical peptides exist, how they're supposed to work, and where the evidence gaps lie — helping consumers and clinicians separate marketing claims from science.","specificNumbers":"","methodology":"Narrative review of published literature on topical peptide use in dermatology and cosmetology, covering the evolution from early peptide discovery through modern cosmeceutical applications.","limitations":"As a narrative review rather than a systematic review or meta-analysis, this paper does not quantitatively assess the strength of evidence across studies. The authors acknowledge that clinical proof of efficacy for many cosmeceutical peptides remains limited."},{"rthcId":"RPEP-03425","title":"Physico-chemical characteristics and fibril-forming capacity of carp swim bladder collagens and exploration of their potential bioactive peptides by in silico approaches.","authors":"Pal, Gaurav Kumar; Suresh, P V","year":2017,"journal":"International journal of biological macromolecules, 101, 304-313","doi":"10.1016/j.ijbiomac.2017.03.061","pmid":"28315441","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03426","title":"Epigenetic mechanisms of alcoholism and stress-related disorders.","authors":"Palmisano, Martina; Pandey, Subhash C","year":2017,"journal":"Alcohol (Fayetteville, N.Y.), 60, 7-18","doi":"10.1016/j.alcohol.2017.01.001","pmid":"28477725","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies common epigenetic mechanisms — histone deacetylation and DNA methylation — that regulate neuropeptide expression in both alcoholism and stress disorders. BDNF, CRF, NPY, and opioid peptides (nociceptin, dynorphin) are key molecules whose expression is altered by epigenetic modifications in specific brain regions. Histone deacetylases and methyltransferases have been identified as shared molecular mechanisms driving the interaction between stress and alcohol dependence, making them promising therapeutic targets.","whyItMatters":"Alcoholism and stress disorders frequently co-occur, but the molecular mechanisms connecting them have been unclear. This review shows that epigenetic changes to neuropeptide genes — particularly NPY and opioid peptides — may be the common thread. This is therapeutically significant because epigenetic modifications are potentially reversible. HDAC inhibitors and other epigenetic drugs could theoretically restore normal neuropeptide function and break the cycle of stress-driven drinking.","specificNumbers":"","methodology":"Narrative review synthesizing evidence from animal models and human studies on epigenetic mechanisms in alcoholism and stress-related disorders, with focus on chromatin remodeling enzymes and their effects on neuropeptide and growth factor expression in the brain.","limitations":"This is a narrative review from 2017, and the field of epigenetics in addiction has continued to evolve. Most evidence comes from animal models, and translation to human epigenetic mechanisms is uncertain. The complexity of epigenetic regulation means that targeting one enzyme (e.g., HDACs) affects many genes beyond the neuropeptides of interest, potentially causing unintended effects. Clinical evidence for epigenetic therapies in alcoholism remains limited."},{"rthcId":"RPEP-03427","title":"Fasting Ghrelin Levels Are Decreased in Obese Subjects and Are Significantly Related With Insulin Resistance and Body Mass Index.","authors":"Papandreou, Dimitrios; Karavolias, Christos; Arvaniti, Fotini; Kafeza, Eleana; Sidawi, Fatima","year":2017,"journal":"Open access Macedonian journal of medical sciences, 5(6), 699-702","doi":"10.3889/oamjms.2017.182","pmid":"29104675","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03428","title":"Intranasal oxytocin treatment for social deficits and biomarkers of response in children with autism.","authors":"Parker, Karen J; Oztan, Ozge; Libove, Robin A; Sumiyoshi, Raena D; Jackson, Lisa P; Karhson, Debra S; Summers, Jacqueline E; Hinman, Kyle E; Motonaga, Kara S; Phillips, Jennifer M; Carson, Dean S; Garner, Joseph P; Hardan, Antonio Y","year":2017,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 114(30), 8119-8124","doi":"10.1073/pnas.1705521114","pmid":"28696286","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03429","title":"A RaPID way to discover nonstandard macrocyclic peptide modulators of drug targets.","authors":"Passioura, Toby; Suga, Hiroaki","year":2017,"journal":"Chemical communications (Cambridge, England), 53(12), 1931-1940","doi":"10.1039/c6cc06951g","pmid":"28091672","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03430","title":"Antimicrobial peptides (AMPs): The quintessential 'offense and defense' molecules are more than antimicrobials.","authors":"Patel, Seema; Akhtar, Nadeem","year":2017,"journal":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 95, 1276-1283","doi":"10.1016/j.biopha.2017.09.042","pmid":"28938518","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03431","title":"Renin-angiotensin-aldosterone (RAAS): The ubiquitous system for homeostasis and pathologies.","authors":"Patel, Seema; Rauf, Abdur; Khan, Haroon; Abu-Izneid, Tareq","year":2017,"journal":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 94, 317-325","doi":"10.1016/j.biopha.2017.07.091","pmid":"28772209","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03432","title":"Transdermal Iontophoretic Delivery of Lysine-Proline-Valine (KPV) Peptide Across Microporated Human Skin.","authors":"Pawar, Kasturi; Kolli, Chandra S; Rangari, Vijaya K; Babu, R Jayachandra","year":2017,"journal":"Journal of pharmaceutical sciences, 106(7), 1814-1820","doi":"10.1016/j.xphs.2017.03.017","pmid":"28343991","tags":["kpv-peptide","peptide-delivery"],"studyType":"In Vitro Laboratory Study","evidenceStrength":"early-stage","keyFinding":"KPV peptide cannot cross the skin by passive diffusion — levels were undetectable. But combining two enhancement technologies dramatically changed this: microneedles alone increased permeation to 4.4 μg/cm²/h, iontophoresis (electrical current) alone was 8-fold better than microneedles, and combining both technologies boosted delivery 35-fold over microneedles alone.\n\nSkin retention also improved dramatically — 10-fold higher KPV was retained in the skin when using iontophoresis or the combination approach. Confocal imaging confirmed the peptide penetrated beyond 100 μm depth, reaching the lower epidermis.","whyItMatters":"KPV is a potent anti-inflammatory peptide, but like most peptides, it can't cross the skin barrier on its own — making injection the only option. This study demonstrates a path toward needle-free KPV delivery through the skin using microneedles and electrical current. If this approach translates to clinical use, it could make KPV accessible as a topical anti-inflammatory treatment.","specificNumbers":"Passive diffusion: undetectable · microneedles: 4.4 μg/cm²/h · iontophoresis: 8× microneedles · combination: 35× microneedles · skin retention: 10× passive · penetration depth: >100 μm","methodology":"In vitro permeation study using dermatomed (thickness-controlled) human skin. Researchers tested four delivery approaches: passive diffusion, microneedle pre-treatment alone, iontophoresis alone, and microneedles plus iontophoresis combined. They varied current strength, KPV concentration, and duration. Permeation and skin retention were quantified, and confocal microscopy with fluorescently-labeled KPV was used to visualize penetration depth.","limitations":"This is an in vitro study using excised human skin — it does not account for blood flow, immune responses, or systemic absorption that would occur in living tissue. No animal or human in vivo testing was performed. The anti-inflammatory effect of the delivered KPV was not measured — only the physical delivery was assessed. Long-term skin safety of repeated iontophoresis and microneedling was not evaluated."},{"rthcId":"RPEP-03433","title":"Substance P promotes hepatic stellate cell proliferation and activation via the TGF-β1/Smad-3 signaling pathway.","authors":"Peng, Lei; Jia, Xiaoqing; Zhao, Jianjian; Cui, Ruibing; Yan, Ming","year":2017,"journal":"Toxicology and applied pharmacology, 329, 293-300","doi":"10.1016/j.taap.2017.06.020","pmid":"28647476","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03434","title":"The dual role of cathelicidins in systemic inflammation.","authors":"Pinheiro da Silva, Fabiano; Machado, Marcel Cerqueira César","year":2017,"journal":"Immunology letters, 182, 57-60","doi":"10.1016/j.imlet.2017.01.004","pmid":"28082134","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03435","title":"Substance P and the neurokinin-1 receptor expression in dog ileum with and without inflammation.","authors":"Polidoro, Giulia; Giancola, Fiorella; Fracassi, Federico; Pietra, Marco; Bettini, Giuliano; Asti, Martina; Chiocchetti, Roberto","year":2017,"journal":"Research in veterinary science, 114, 297-307","doi":"10.1016/j.rvsc.2017.06.002","pmid":"28628846","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In dogs with spontaneous ileal inflammation (n=8) compared to healthy controls (n=7), the percentage of Substance P-producing neurons was similar in both the myenteric plexus (15–16%) and submucosal plexus (24–26%). However, key differences emerged in receptor distribution: muscle cells and immune cells in inflamed tissue overexpressed NK1R immunoreactivity, while nitrergic (nNOS-positive) neurons expressing NK1R showed a trend toward decrease in inflamed dogs (41% vs 65%, P=0.11).\n\nSP-immunoreactive mucosal nerve fibers also trended toward decreased density in inflamed tissue (P=0.07). These findings suggest that inflammation shifts NK1R from neuronal to non-neuronal tissue compartments, potentially altering how Substance P signaling affects gut function.","whyItMatters":"NK1R antagonist drugs are already used clinically (aprepitant for chemotherapy-induced nausea), and there's growing interest in targeting Substance P signaling for inflammatory bowel conditions. This study provides a nuanced picture: while NK1R overexpression on immune cells supports the rationale for NK1R antagonists in gut inflammation, the simultaneous role of NK1R in neuronal motility circuits means such drugs could cause motility disorders as a side effect. Understanding this dual role is critical for drug development.","specificNumbers":"","methodology":"This was a comparative immunohistochemical study of ileal tissue from 7 control dogs and 8 dogs with spontaneous ileal inflammation. Researchers quantified the percentage of Substance P-immunoreactive enteric neurons, SP-positive nerve fiber density, NK1R-expressing neurons (including nitrergic subpopulations), and NK1R expression in non-neuronal cells (muscle and immune cells) across both myenteric and submucosal plexuses.","limitations":"This is a small study (7 control, 8 inflamed dogs) with limited statistical power — several important trends (mucosal nerve fiber density, nitrergic NK1R expression) did not reach statistical significance. The study used naturally occurring canine inflammation, which strengthens ecological validity but introduces variability in disease type and severity. The findings are from dogs and may not directly translate to human intestinal inflammation. The functional consequences of NK1R redistribution were not directly tested."},{"rthcId":"RPEP-03436","title":"Urinary peptide-based classifier CKD273: towards clinical application in chronic kidney disease.","authors":"Pontillo, Claudia; Mischak, Harald","year":2017,"journal":"Clinical kidney journal, 10(2), 192-201","doi":"10.1093/ckj/sfx002","pmid":"28694965","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03437","title":"Antagonists of growth hormone-releasing hormone inhibit proliferation induced by inflammation in prostatic epithelial cells.","authors":"Popovics, Petra; Schally, Andrew V; Salgueiro, Luis; Kovacs, Krisztina; Rick, Ferenc G","year":2017,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 114(6), 1359-1364","doi":"10.1073/pnas.1620884114","pmid":"28123062","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03438","title":"Duodenal and ileal glucose infusions differentially alter gastrointestinal peptides, appetite response, and food intake: a tube feeding study.","authors":"Poppitt, Sally D; Shin, Hyun Sang; McGill, Anne-Thea; Budgett, Stephanie C; Lo, Kim; Pahl, Malcolm; Duxfield, Janice; Lane, Mark; Ingram, John R","year":2017,"journal":"The American journal of clinical nutrition, 106(3), 725-735","doi":"10.3945/ajcn.117.157248","pmid":"28701300","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03439","title":"Nonclassical Size Dependence of Permeation Defines Bounds for Passive Adsorption of Large Drug Molecules.","authors":"Pye, Cameron R; Hewitt, William M; Schwochert, Joshua; Haddad, Terra D; Townsend, Chad E; Etienne, Lyns; Lao, Yongtong; Limberakis, Chris; Furukawa, Akihiro; Mathiowetz, Alan M; Price, David A; Liras, Spiros; Lokey, R Scott","year":2017,"journal":"Journal of medicinal chemistry, 60(5), 1665-1672","doi":"10.1021/acs.jmedchem.6b01483","pmid":"28059508","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03440","title":"Amylin and its G-protein-coupled receptor: A probable pathological process and drug target for Alzheimer's disease.","authors":"Qiu, Wei Qiao","year":2017,"journal":"Neuroscience, 356, 44-51","doi":"10.1016/j.neuroscience.2017.05.024","pmid":"28528968","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03441","title":"Molecular Integration of Incretin and Glucocorticoid Action Reverses Immunometabolic Dysfunction and Obesity.","authors":"Quarta, Carmelo; Clemmensen, Christoffer; Zhu, Zhimeng; Yang, Bin; Joseph, Sini S; Lutter, Dominik; Yi, Chun-Xia; Graf, Elisabeth; García-Cáceres, Cristina; Legutko, Beata; Fischer, Katrin; Brommage, Robert; Zizzari, Philippe; Franklin, Bernardo S; Krueger, Martin; Koch, Marco; Vettorazzi, Sabine; Li, Pengyun; Hofmann, Susanna M; Bakhti, Mostafa; Bastidas-Ponce, Aimée; Lickert, Heiko; Strom, Tim M; Gailus-Durner, Valerie; Bechmann, Ingo; Perez-Tilve, Diego; Tuckermann, Jan; Hrabě de Angelis, Martin; Sandoval, Darleen; Cota, Daniela; Latz, Eicke; Seeley, Randy J; Müller, Timo D; DiMarchi, Richard D; Finan, Brian; Tschöp, Matthias H","year":2017,"journal":"Cell metabolism, 26(4), 620-632.e6","doi":"10.1016/j.cmet.2017.08.023","pmid":"28943448","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03442","title":"Dose-dependent social-cognitive effects of intranasal oxytocin delivered with novel Breath Powered device in adults with autism spectrum disorder: a randomized placebo-controlled double-blind crossover trial.","authors":"Quintana, D S; Westlye, L T; Hope, S; Nærland, T; Elvsåshagen, T; Dørum, E; Rustan, Ø; Valstad, M; Rezvaya, L; Lishaugen, H; Stensønes, E; Yaqub, S; Smerud, K T; Mahmoud, R A; Djupesland, P G; Andreassen, O A","year":2017,"journal":"Translational psychiatry, 7(5), e1136","doi":"10.1038/tp.2017.103","pmid":"28534875","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Low-dose intranasal oxytocin (8 IU) delivered via a novel Breath Powered device significantly increased emotional salience of faces in adults with autism (P=0.02, d=0.63, η²=0.18), while the higher dose (24 IU) did not reach statistical significance (P=0.12, d=0.4). Remarkably, the 8 IU effects occurred without significantly increasing blood plasma oxytocin levels, suggesting direct nose-to-brain delivery. No significant effects were found on other social-cognitive tasks (reading the mind in the eyes, emotional dot probe, face morphing).","whyItMatters":"Oxytocin research for autism has been hindered by inconsistent results, partly due to poor nasal delivery and unknown dose-response relationships. This is the first trial to show that less oxytocin may actually work better than more, and that a specialized delivery device can target the brain directly — potentially resolving why previous oxytocin trials in autism produced mixed results.","specificNumbers":"n=17 · 8 IU vs 24 IU vs placebo · 8 IU: P=0.02, d=0.63 · 24 IU: P=0.12, d=0.4 · η²=0.18 · no blood plasma increase at 8 IU","methodology":"Double-blind, crossover, randomized, placebo-controlled trial. 17 male adults with ASD received single doses of 8 IU oxytocin, 24 IU oxytocin, or placebo via a Breath Powered intranasal device in randomized sequence. After each dose, participants completed four social-cognitive tasks measuring emotion salience, emotion recognition, attentional bias, and face processing. Blood plasma oxytocin levels were measured.","limitations":"Very small sample (n=17), all male. Single-dose crossover design cannot assess long-term effects or repeated dosing. Only one of four social-cognitive tasks showed significant improvement. The Breath Powered device is novel and not widely available. The finding of no plasma increase at the effective dose, while interesting, requires replication."},{"rthcId":"RPEP-03443","title":"Production of angiotensin I converting enzyme inhibitory (ACE-I) peptides during milk fermentation and their role in reducing hypertension.","authors":"Rai, Amit Kumar; Sanjukta, Samurailatpam; Jeyaram, Kumaraswamy","year":2017,"journal":"Critical reviews in food science and nutrition, 57(13), 2789-2800","doi":"10.1080/10408398.2015.1068736","pmid":"26463100","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"ACE-inhibitory peptides produced during milk fermentation are resistant to gastrointestinal digestion and can inhibit ACE in the renin-angiotensin system in their intact form. Their production and potency depend on multiple factors: the type of starter culture (lactic acid bacteria species, yeast), the milk protein substrate (casein type, whey protein), the specific peptide composition, and pre- and post-fermentation processing.\n\nThe antihypertensive effects of fermented milk products have been confirmed through in vitro studies, animal models, and human clinical trials. Several ACE-inhibitory peptides from fermented milk are now available in commercial products marketed for blood pressure support.","whyItMatters":"Hypertension affects over a billion people worldwide and is the leading risk factor for cardiovascular disease. While pharmaceutical ACE inhibitors are effective, they have side effects. Food-derived bioactive peptides offer a complementary approach — potentially preventing hypertension or reducing medication burden through everyday foods. Understanding what makes these peptides effective can guide the development of optimized functional dairy products.","specificNumbers":"","methodology":"Comprehensive narrative review of published literature on ACE-inhibitory peptides from fermented milk, covering peptide identification, production factors, gastrointestinal stability, and evidence from in vitro, animal, and human studies.","limitations":"As a review, no new experimental data are presented. The blood pressure-lowering effects seen in clinical trials are generally modest compared to pharmaceutical ACE inhibitors. Bioavailability varies significantly between peptides and between individuals. Not all fermented milk products contain therapeutic concentrations of ACE-inhibitory peptides. The review does not comprehensively address dose-response relationships or long-term efficacy."},{"rthcId":"RPEP-03444","title":"Conjugated nanoliposome with the HER2/neu-derived peptide GP2 as an effective vaccine against breast cancer in mice xenograft model.","authors":"Razazan, Atefeh; Behravan, Javad; Arab, Atefeh; Barati, Nastaran; Arabi, Leila; Gholizadeh, Zahra; Hatamipour, Mahdi; Reza Nikpoor, Amin; Momtazi-Borojeni, Amir Abbas; Mosaffa, Fatemeh; Ghahremani, Mohamad Hosein; Jaafari, Mahmoud Reza","year":2017,"journal":"PloS one, 12(10), e0185099","doi":"10.1371/journal.pone.0185099","pmid":"29045460","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The Lip-DOPE-MPL-GP2 formulation generated the highest IFN-γ+ CD8+ T cell and cytotoxic T lymphocyte responses among all tested formulations, as measured by ELISpot and flow cytometry. In both prophylactic (vaccination before tumor challenge) and therapeutic (vaccination after tumor establishment) experiments, mice immunized with this formulation had smaller tumors and longer survival compared to other groups. The combination of DOPE (fusogenic lipid) and MPL (adjuvant) was key to both the immune response and anti-tumor efficacy.","whyItMatters":"GP2 is a HER2-derived peptide already in human clinical trials as a breast cancer vaccine. This study shows that delivering it via nanoliposomes dramatically enhances the immune response compared to standard vaccine formulations. If this improved delivery translates to humans, it could make peptide-based cancer vaccines far more effective for the approximately 15-20% of breast cancers that overexpress HER2.","specificNumbers":"","methodology":"GP2 peptide was conjugated to maleimide-mPEG2000-DSPE micelles and post-inserted into liposomes containing DMPC, DMPG, DOPE, and MPL. BALB/c mice were immunized with various formulations. Immune responses were evaluated by ELISpot and intracellular cytokine flow cytometry. Anti-tumor efficacy was tested in both prophylactic and therapeutic TUBO xenograft models measuring tumor size and survival.","limitations":"This is a mouse study using a xenograft model, which may not accurately predict human immune responses or therapeutic outcomes. The TUBO model is a specific mouse breast cancer system that may differ from human HER2-positive tumors. Specific tumor size reductions and survival data are not quantified in the abstract. Long-term efficacy and safety in larger animal models or humans have not been assessed."},{"rthcId":"RPEP-03445","title":"The safety of albiglutide for the treatment of type 2 diabetes.","authors":"Rendell, Marc S","year":2017,"journal":"Expert opinion on drug safety, 16(9), 1089-1097","doi":"10.1080/14740338.2017.1351538","pmid":"28678550","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03446","title":"Post-prandial anorexigenic gut peptide, appetite and glucometabolic responses at different eating rates in obese patients undergoing laparoscopic sleeve gastrectomy.","authors":"Rigamonti, Antonello Emilio; Bini, Silvia; Rocco, Maria Cristina; Giardini, Vittorio; Massimini, Diego; Crippa, Maria Grazia; Saluzzi, Antonella; Casati, Marco; Marazzi, Nicoletta; Perotti, Mario; Cimino, Vincenzo; Grassi, Guido; Sartorio, Alessandro; Pincelli, Angela Ida","year":2017,"journal":"Endocrine, 55(1), 113-123","doi":"10.1007/s12020-016-0933-6","pmid":"27022941","tags":[],"studyType":"Clinical Study","evidenceStrength":"preliminary","keyFinding":"Contrary to expectations, the appetite-suppressing gut peptides GLP-1 and PYY do not appear to be major drivers of weight loss after sleeve gastrectomy. In 10 obese patients studied before and 3 months after surgery, GLP-1 release after meals was not stimulated regardless of eating speed or surgical status. PYY levels did increase after surgery (higher post-op than pre-op), but the speed of eating made no difference.\n\nInterestingly, fast eating produced greater satiety than slow eating in both pre- and post-operative states, contradicting common dietary advice. Hunger and satiety responses to food were similar before and after surgery. Sleeve gastrectomy did improve insulin resistance regardless of eating speed. The authors conclude that anorexigenic gut peptide responses play a \"negligible\" role in sleeve gastrectomy-induced weight loss, suggesting other mechanisms (mechanical restriction, altered ghrelin, neural signaling) are more important.","whyItMatters":"A leading theory for why bariatric surgery causes weight loss is that it changes gut peptide secretion — boosting appetite-suppressing peptides like GLP-1 and PYY. This study challenges that theory for sleeve gastrectomy specifically, finding that GLP-1 wasn't stimulated at all and PYY changes were modest. Understanding which mechanisms actually drive surgical weight loss is critical for developing peptide-based alternatives to surgery.","specificNumbers":"n=10 · Pre- and post-LSG (3 months) · GLP-1 not stimulated by meals in either state · PYY increased post-op vs. pre-op · Fast feeding = higher satiety than slow · Insulin resistance improved post-surgery","methodology":"Prospective clinical study in 10 obese patients undergoing laparoscopic sleeve gastrectomy. Patients were tested before and 3 months after surgery with fast and slow meal challenges. Circulating GLP-1, PYY, glucose, insulin, and triglycerides were measured at multiple timepoints. Visual analogue scales assessed hunger and satiety. Responses were compared across feeding speeds and surgical states.","limitations":"Very small sample size of only 10 patients severely limits statistical power and generalizability. Three months post-surgery may be too early to capture long-term changes in gut peptide secretion. The study only measured GLP-1 and PYY, missing other gut peptides like CCK, oxyntomodulin, and ghrelin that may be more relevant. No non-obese control group for comparison."},{"rthcId":"RPEP-03447","title":"Targeting NPY, CRF/UCNs and NPS Neuropeptide Systems to Treat Alcohol Use Disorder (AUD).","authors":"Rodriguez, Francisco D; Coveñas, Rafael","year":2017,"journal":"Current medicinal chemistry, 24(23), 2528-2558","doi":"10.2174/0929867324666170316120836","pmid":"28302012","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03448","title":"The impact of EndoBarrier gastrointestinal liner in obese patients with normal glucose tolerance and in patients with type 2 diabetes.","authors":"Rohde, Ulrich; Federspiel, Cecilie A; Vilmann, Peter; Langholz, Ebbe; Friis, Steffen U; Krakauer, Martin; Rehfeld, Jens F; Holst, Jens J; Vilsbøll, Tina; Knop, Filip K","year":2017,"journal":"Diabetes, obesity & metabolism, 19(2), 189-199","doi":"10.1111/dom.12800","pmid":"27696668","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03449","title":"Helicobacter pylori infection and serum leptin, obestatin, and ghrelin levels in Mexican schoolchildren.","authors":"Romo-González, Carolina; Mendoza, Eugenia; Mera, Robertino M; Coria-Jiménez, Rafael; Chico-Aldama, Patricia; Gomez-Diaz, Rita; Duque, Ximena","year":2017,"journal":"Pediatric research, 82(4), 607-613","doi":"10.1038/pr.2017.69","pmid":"28422951","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03450","title":"Traumatic stress-induced persistent changes in DNA methylation regulate neuropeptide Y expression in rat jejunum.","authors":"Sagarkar, S; Mahajan, S; Choudhary, A G; Borkar, C D; Kokare, D M; Sakharkar, A J","year":2017,"journal":"Neurogastroenterology and motility, 29(9)","doi":"10.1111/nmo.13074","pmid":"28418087","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03451","title":"Systematic Design of Trypsin Cleavage Site Mutated Exendin4-Cysteine 1, an Orally Bioavailable Glucagon-Like Peptide-1 Receptor Agonist.","authors":"Sai, Wenbo; Tian, Hong; Yang, Kangmin; Tang, Daoqi; Bao, Jinxiao; Ge, Yang; Song, Xiaoda; Zhang, Yu; Luo, Cheng; Gao, Xiangdong; Yao, Wenbing","year":2017,"journal":"International journal of molecular sciences, 18(3)","doi":"10.3390/ijms18030578","pmid":"28282854","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Using Rosetta Design and Amber molecular modeling software, researchers designed and screened exendin-4 analogs with mutations at trypsin cleavage sites. The top candidate, TSME-1, retained biological activity comparable to native exendin-4 while being almost completely resistant to trypsin digestion. When administered orally to C57BL/6J mice, TSME-1 significantly normalized blood glucose levels in glucose tolerance tests and showed significantly higher oral bioavailability than both native exendin-4 and the intermediate exendin4-cysteine analog.","whyItMatters":"Millions of people with type 2 diabetes use injectable GLP-1 receptor agonists, but the need for injections reduces patient compliance. Creating an oral version has been a major pharmaceutical goal. This study demonstrates a systematic computational approach to engineering peptides that survive digestion, which could apply not just to exendin-4 but to many other therapeutic peptides.","specificNumbers":"","methodology":"Researchers used computational protein design tools (Rosetta Design and Amber) to systematically identify and mutate trypsin cleavage sites in exendin4-cysteine while preserving GLP-1 receptor binding and activation. Candidates were screened for both biological activity and trypsin resistance. The lead candidate (TSME-1) was tested in vivo using intraperitoneal glucose tolerance tests in C57BL/6J mice, with oral bioavailability compared across exendin-4, exendin4-cysteine, and TSME-1.","limitations":"This is a preclinical mouse study. While TSME-1 resists trypsin, the human digestive tract contains many other proteases that weren't tested. Oral bioavailability numbers in mice may not predict human bioavailability. The study doesn't address manufacturing scalability, stability during storage, or formulation optimization. No comparison to existing oral semaglutide technology was made."},{"rthcId":"RPEP-03452","title":"Targeted high-resolution quadrupole-Orbitrap mass spectrometry analyses reveal a significant reduction of tachykinin and opioid neuropeptides level in PC1 and PC2 mutant mouse spinal cords.","authors":"Saidi, Mouna; Beaudry, Francis","year":2017,"journal":"Neuropeptides, 65, 37-44","doi":"10.1016/j.npep.2017.04.007","pmid":"28476408","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03453","title":"Ser422 phosphorylation blocks human Tau cleavage by caspase-3: Biochemical implications to Alzheimer's Disease.","authors":"Sandhu, Priya; Naeem, Mansur Mohammad; Lu, Chunyu; Kumarathasan, Premkumari; Gomes, James; Basak, Ajoy","year":2017,"journal":"Bioorganic & medicinal chemistry letters, 27(3), 642-652","doi":"10.1016/j.bmcl.2016.11.087","pmid":"27989667","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03454","title":"Guardians of the Gut: Enteric Defensins.","authors":"Sankaran-Walters, Sumathi; Hart, Ronald; Dills, Chantelle","year":2017,"journal":"Frontiers in microbiology, 8, 647","doi":"10.3389/fmicb.2017.00647","pmid":"28469609","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03455","title":"Prognostic value of plasma apelin concentrations at admission in patients with ST-segment elevation acute myocardial infarction.","authors":"Sans-Roselló, Jordi; Casals, Gregori; Rossello, Xavier; González de la Presa, Bernardino; Vila, Montserrat; Duran-Cambra, Albert; Morales-Ruiz, Manuel; Ferrero-Gregori, Andreu; Jiménez, Wladimiro; Sionis, Alessandro","year":2017,"journal":"Clinical biochemistry, 50(6), 279-284","doi":"10.1016/j.clinbiochem.2016.11.018","pmid":"27889567","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 250 consecutive STEMI patients, increased plasma apelin concentrations at admission independently predicted 6-month all-cause mortality after adjusting for age, diabetes, systolic blood pressure, heart rate, glomerular filtration rate, Killip class, left ventricular ejection fraction, BNP, and sensitive troponin I.\n\nCombining apelin with BNP and troponin I further improved predictive accuracy compared to any single biomarker. Notably, apelin levels were associated with markers of ischemic heart failure severity (reflecting the heart's functional decline) but not with markers of ischemic insult severity (reflecting the acute damage) — suggesting apelin reflects the heart failure response rather than the ischemic injury itself.","whyItMatters":"Quickly identifying which heart attack patients are at highest risk of dying is critical for clinical decision-making. Standard biomarkers like BNP and troponin are already used, but adding apelin to the panel improved prediction. The finding that apelin reflects heart failure severity rather than ischemic damage severity suggests it captures a different aspect of cardiovascular stress — potentially identifying patients who need more aggressive heart failure management after their acute event.","specificNumbers":"","methodology":"This was a prospective observational study that consecutively enrolled 250 patients with STEMI from January 2012 to January 2013 at a single center. Plasma apelin, BNP, and sensitive troponin I were measured from blood samples collected at hospital admission. Clinical, hemodynamic, and laboratory variables were recorded. The primary outcome was all-cause mortality at 6-month follow-up. Multivariable regression was used to assess apelin's independent prognostic value.","limitations":"This is a single-center observational study with a moderate sample size (250 patients). The study cannot determine whether elevated apelin is a cause, consequence, or merely a marker of worse outcomes. Apelin was measured only at admission, so the prognostic value of serial measurements is unknown. The specific cut-off values for clinical use were not established. External validation in larger, multicenter cohorts is needed."},{"rthcId":"RPEP-03456","title":"Evaluation of the in vitro effect of Boldo and Meadowsweet plant extracts on the expression of antimicrobial peptides and inflammatory markers in canine keratinocytes.","authors":"Santoro, Domenico; Ahrens, Kim; Vesny, Ryan; Navarro, Christelle; Gatto, Hugues; Marsella, Rosanna","year":2017,"journal":"Research in veterinary science, 115, 255-262","doi":"10.1016/j.rvsc.2017.05.021","pmid":"28549300","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03457","title":"Lactoferrin-derived Peptides Active towards Influenza: Identification of Three Potent Tetrapeptide Inhibitors.","authors":"Scala, Maria Carmina; Sala, Marina; Pietrantoni, Agostina; Spensiero, Antonia; Di Micco, Simone; Agamennone, Mariangela; Bertamino, Alessia; Novellino, Ettore; Bifulco, Giuseppe; Gomez-Monterrey, Isabel M; Superti, Fabiana; Campiglia, Pietro","year":2017,"journal":"Scientific reports, 7(1), 10593","doi":"10.1038/s41598-017-10492-x","pmid":"28878220","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03458","title":"Metabolic Response of Human Osteoarthritic Cartilage to Biochemically Characterized Collagen Hydrolysates.","authors":"Schadow, Saskia; Simons, Viktor S; Lochnit, Guenter; Kordelle, Jens; Gazova, Zuzana; Siebert, Hans-Christian; Steinmeyer, Juergen","year":2017,"journal":"International journal of molecular sciences, 18(1)","doi":"10.3390/ijms18010207","pmid":"28117674","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"No collagen hydrolysate modulated collagen biosynthesis in human knee cartilage explants — the primary benefit these supplements claim to provide.\n\nThe products showed disparate effects: Peptan F 2000 (fish) enhanced the activities of cartilage-degrading aggrecanases ADAMTS4 and ADAMTS5 in vitro, without proteoglycan loss from tissue. Mobiforte (porcine) showed the opposite aggrecanase effect. Mobiforte and Peptan F 5000 elevated IL-6, MMP-1, MMP-3, and MMP-13 in cartilage explants — all markers of inflammation and cartilage destruction — while Peptan F 2000 did not.\n\nBiophysical analysis (MALDI-TOF-MS, NMR, AFM) revealed marked differences in total peptide number and shared peptides between the fish and porcine products.","whyItMatters":"Collagen hydrolysate supplements are a billion-dollar market, widely promoted for joint health without rigorous regulation. This study reveals that not only do these products vary enormously in their peptide composition, but some may actually increase inflammation and cartilage-degrading enzymes in osteoarthritic tissue. The finding that no product stimulated collagen production directly challenges the core marketing claim of these supplements.","specificNumbers":"","methodology":"Three commercial collagen hydrolysate products (2 fish-derived, 1 porcine-derived) were characterized using MALDI-TOF mass spectrometry, NMR spectroscopy, and atomic force microscopy. Effects on human osteoarthritic knee cartilage explants were tested using a novel dual radiolabeling procedure for collagen biosynthesis, ELISA for cytokines and MMPs, and in vitro aggrecanase activity assays.","limitations":"The study was conducted using human cartilage explants in vitro, which may not fully replicate in vivo conditions. Only three commercial products were tested. The peptide concentrations used may not reflect the levels achieved in joint tissue after oral supplementation. The study does not address whether the observed effects translate to clinical outcomes. Bioavailability of collagen peptides reaching joint tissue after oral consumption is a separate question not addressed here."},{"rthcId":"RPEP-03459","title":"Substance P and the Neurokinin-1 Receptor: The New CRF.","authors":"Schank, Jesse R; Heilig, Markus","year":2017,"journal":"International review of neurobiology, 136, 151-175","doi":"10.1016/bs.irn.2017.06.008","pmid":"29056150","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03460","title":"Pharmacotherapy of 'treatment resistant' type 2 diabetes.","authors":"Scheen, André J","year":2017,"journal":"Expert opinion on pharmacotherapy, 18(5), 503-515","doi":"10.1080/14656566.2017.1297424","pmid":"28276972","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03461","title":"In silico and cell-based analyses reveal strong divergence between prediction and observation of T-cell-recognized tumor antigen T-cell epitopes.","authors":"Schmidt, Julien; Guillaume, Philippe; Dojcinovic, Danijel; Karbach, Julia; Coukos, George; Luescher, Immanuel","year":2017,"journal":"The Journal of biological chemistry, 292(28), 11840-11849","doi":"10.1074/jbc.M117.789511","pmid":"28536262","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Starting with 41 peptides predicted by in silico algorithms as the highest-affinity binders to HLA-A*0201, the study found a dramatic funnel of attrition:\n\n- 41 peptides predicted as strong binders\n- 19 actually showed strong binding to HLA-A2\n- 10 formed stable HLA-A2-peptide complexes and induced CD8+ T cells in transgenic mice\n- Only 5 induced T cell responses in PBMCs from ESO-vaccinated melanoma patients\n\nThe 5 immunogenic peptides shared features not predicted by algorithms: strong binding, high complex stability, and multiple large hydrophobic and aromatic amino acids. This reveals that current prediction tools capture only part of what makes a peptide immunogenic in humans.","whyItMatters":"Personalized cancer vaccines depend on correctly predicting which tumor peptides will trigger an immune response. If prediction algorithms have a high false-positive rate — as this study shows — researchers waste time and money testing peptides that won't work. Improving prediction accuracy could accelerate cancer vaccine development by focusing resources on the peptides most likely to be immunogenic in actual patients.","specificNumbers":"","methodology":"Researchers used in silico algorithms to predict the top 41 HLA-A*0201-binding 8-11mer peptides from the NY-ESO-1 tumor antigen. They then tested binding strength and kinetic complex stability using biochemical assays. Immunogenicity was assessed in HLA-A2-transgenic mice and in peripheral blood mononuclear cells from melanoma patients who had received ESO vaccination. Results were compared against the algorithm predictions.","limitations":"The study focused on a single tumor antigen (NY-ESO-1) and a single HLA allele (HLA-A*0201), which may not represent the full diversity of antigen-HLA combinations in cancer. The patient cohort was limited to melanoma patients who had received ESO vaccination. The 5 immunogenic peptides identified may not generalize to other tumor antigens or HLA types. Mouse transgenic models don't perfectly replicate human immune responses."},{"rthcId":"RPEP-03462","title":"Expression, Functional Characterization, and Solid-State NMR Investigation of the G Protein-Coupled GHS Receptor in Bilayer Membranes.","authors":"Schrottke, Stefanie; Kaiser, Anette; Vortmeier, Gerrit; Els-Heindl, Sylvia; Worm, Dennis; Bosse, Mathias; Schmidt, Peter; Scheidt, Holger A; Beck-Sickinger, Annette G; Huster, Daniel","year":2017,"journal":"Scientific reports, 7, 46128","doi":"10.1038/srep46128","pmid":"28387359","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03463","title":"Calcitonin Gene-Related Peptide-Targeted Therapies for Migraine and Cluster Headache: A Review.","authors":"Schuster, Nathaniel M; Rapoport, Alan M","year":2017,"journal":"Clinical neuropharmacology, 40(4), 169-174","doi":"10.1097/WNF.0000000000000227","pmid":"28644160","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03464","title":"Nanofibers of Human Tropoelastin-inspired peptides: Structural characterization and biological properties.","authors":"Secchi, Valeria; Franchi, Stefano; Fioramonti, Marco; Polzonetti, Giovanni; Iucci, Giovanna; Bochicchio, Brigida; Battocchio, Chiara","year":2017,"journal":"Materials science & engineering. C, Materials for biological applications, 77, 927-934","doi":"10.1016/j.msec.2017.04.019","pmid":"28532113","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03465","title":"Structure-Related Roles for the Conservation of the HIV-1 Fusion Peptide Sequence Revealed by Nuclear Magnetic Resonance.","authors":"Serrano, Soraya; Huarte, Nerea; Rujas, Edurne; Andreu, David; Nieva, José L; Jiménez, María Angeles","year":2017,"journal":"Biochemistry, 56(41), 5503-5511","doi":"10.1021/acs.biochem.7b00745","pmid":"28930470","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Two fusion peptide surrogates with equal hydrophobicity but different sequences were compared:\n\n- wtFP-tag (wild-type LFLGFLG): preserved α-helical conformation with a Gly-rich ridge in DPC micelles (membrane mimic); assembled into trimers in membranes (detected by Western blot)\n- scrFP-tag (scrambled FGLLGFL): maintained helical structure in low-polarity HFIP solvent but largely lost helical structure in DPC micelles; failed to form membrane oligomers\n\nBoth peptides were tagged with an independently folding epitope sequence for detection without interfering with FP structure. The results demonstrate that the conserved FLGFLG tandem repeat is essential for maintaining the specific helical conformation and trimerization ability required for HIV membrane fusion.","whyItMatters":"Understanding why HIV's fusion peptide sequence is so conserved reveals a potential vulnerability for drug and vaccine design. If the virus cannot tolerate changes to this sequence without losing function, then therapies targeting this exact peptide region may be broadly effective against diverse HIV strains. The finding that sequence order (not just hydrophobicity) determines membrane structure and trimerization provides specific structural features that could be exploited by fusion inhibitor drugs or antibodies targeting the fusion peptide.","specificNumbers":"","methodology":"Wild-type and scrambled HIV fusion peptide variants were synthesized with C-terminal epitope tags. NMR spectroscopy was used to determine three-dimensional structures in two environments: 25% HFIP (nonpolar solvent) and DPC micelles (membrane-mimicking system). Secondary structure content, helical features, and glycine-ridge characteristics were compared between the two sequences. Western blot analysis using the epitope tags assessed oligomerization (trimerization) in membrane environments.","limitations":"The study used synthetic peptide surrogates rather than full-length gp41 protein, which may not perfectly replicate the fusion peptide's behavior in the context of the complete viral spike. DPC micelles are simplified membrane mimics that lack the complexity of biological membranes. Only one scrambled sequence was tested — other permutations might retain more function. The study did not directly test viral infectivity with modified fusion peptides. The epitope tag, while designed to fold independently, could potentially influence some structural measurements."},{"rthcId":"RPEP-03466","title":"Neuromedin B Expression Defines the Mouse Retrotrapezoid Nucleus.","authors":"Shi, Yingtang; Stornetta, Ruth L; Stornetta, Daniel S; Onengut-Gumuscu, Suna; Farber, Emily A; Turner, Stephen D; Guyenet, Patrice G; Bayliss, Douglas A","year":2017,"journal":"The Journal of neuroscience : the official journal of the Society for Neuroscience, 37(48), 11744-11757","doi":"10.1523/JNEUROSCI.2055-17.2017","pmid":"29066557","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03467","title":"Silencing of BCR/ABL Chimeric Gene in Human Chronic Myelogenous Leukemia Cell Line K562 by siRNA-Nuclear Export Signal Peptide Conjugates.","authors":"Shinkai, Yasuhiro; Kashihara, Shinichi; Minematsu, Go; Fujii, Hirofumi; Naemura, Madoka; Kotake, Yojiro; Morita, Yasutaka; Ohnuki, Koichiro; Fokina, Alesya A; Stetsenko, Dmitry A; Filichev, Vyacheslav V; Fujii, Masayuki","year":2017,"journal":"Nucleic acid therapeutics, 27(3), 168-175","doi":"10.1089/nat.2016.0647","pmid":"28355131","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Two siRNA-NES peptide conjugates were synthesized: one linked to a TFIIIA-derived NES peptide and another to an HIV-1 REV-derived NES peptide. The HIV-1 REV conjugate suppressed BCR/ABL expression to 4.0% (96% silencing) at 200 nM and 6.3% at 50 nM. The TFIIIA conjugate suppressed to 8.3% at 200 nM and 11.6% at 50 nM. By comparison, native siRNA only suppressed to 36.3% at 200 nM and 30.2% at 50 nM. Complexing the conjugates with amphiphilic peptideβ7 enabled non-toxic cellular uptake with excellent silencing efficiency.","whyItMatters":"Gene silencing with siRNA has enormous therapeutic potential but is limited by poor cellular uptake and intracellular trafficking. By conjugating siRNA to NES peptides, the researchers achieved near-complete gene silencing at standard doses — and the peptide-based delivery system avoids the toxicity associated with lipid-based transfection agents. This could advance gene therapy for CML and other cancers driven by known gene fusions.","specificNumbers":"","methodology":"Researchers synthesized siRNA-NES peptide conjugates using solid-phase fragment coupling, linking NES peptides (from TFIIIA and HIV-1 REV) to the 5' end of sense strands. They tested gene silencing efficiency in human CML cell line K562 at multiple concentrations. Cellular uptake was achieved using complexation with an amphiphilic carrier peptide (peptideβ7), and cytotoxicity was assessed.","limitations":"This is an in vitro study using a single cell line (K562), and results need validation in animal models and other CML cell lines. The study did not assess off-target gene silencing effects. In vivo pharmacokinetics, biodistribution, and immune responses to the peptide-siRNA conjugates are unknown. The amphiphilic peptide delivery system needs further optimization for in vivo use."},{"rthcId":"RPEP-03468","title":"Identifying Loop-Mediated Protein-Protein Interactions Using LoopFinder.","authors":"Siegert, Timothy R; Bird, Michael; Kritzer, Joshua A","year":2017,"journal":"Methods in molecular biology (Clifton, N.J.), 1561, 255-277","doi":"10.1007/978-1-4939-6798-8_15","pmid":"28236243","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03469","title":"Growth Hormone Secretagogue Treatment in Hypogonadal Men Raises Serum Insulin-Like Growth Factor-1 Levels.","authors":"Sigalos, John T; Pastuszak, Alexander W; Allison, Andrew; Ohlander, Samuel J; Herati, Amin; Lindgren, Mark C; Lipshultz, Larry I","year":2017,"journal":"American journal of men's health, 11(6), 1752-1757","doi":"10.1177/1557988317718662","pmid":"28830317","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03470","title":"Effects of lactoferrin derived peptides on simulants of biological warfare agents.","authors":"Sijbrandij, Tjitske; Ligtenberg, Antoon J; Nazmi, Kamran; Veerman, Enno C I; Bolscher, Jan G M; Bikker, Floris J","year":2017,"journal":"World journal of microbiology & biotechnology, 33(1), 3","doi":null,"pmid":"27832504","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The chimeric peptide LFchimera (combining lactoferricin 17-30 and lactoferampin 265-284) demonstrated the most prominent bactericidal activity, membrane permeabilization, and membrane depolarization against both Gram-positive and Gram-negative bacteria serving as biological warfare agent simulants.\n\nArginine residues were identified as crucial for antimicrobial activity: lysine-to-arginine substitutions increased activity (particularly affecting LFampin265-284), while arginine-to-lysine substitutions decreased activity (particularly in LFcin17-30). This establishes arginine content as a key design parameter for optimizing lactoferrin-derived antimicrobial peptides.","whyItMatters":"Biological threats remain a serious security concern, and existing antibiotics may be ineffective against engineered or naturally resistant pathogens. Antimicrobial peptides offer a fundamentally different killing mechanism (membrane disruption) that is harder for bacteria to develop resistance against. This study provides specific engineering rules for creating more potent lactoferrin-based peptides for biodefense countermeasures.","specificNumbers":"","methodology":"A chimeric peptide was constructed from parts of bovine lactoferricin (LFcin17-30) and lactoferampin (LFampin265-284). Bactericidal activity was tested against Gram-positive and Gram-negative bacteria used as simulants for biological warfare agents. Membrane permeability and membrane polarity changes were measured to characterize the killing mechanism. Amino acid substitutions (lysine-to-arginine and arginine-to-lysine) were systematically tested to determine which residues are critical for activity.","limitations":"The bacteria tested were simulants for biological warfare agents, not the actual threat organisms — results may not directly translate. All testing was in vitro with no animal studies of therapeutic efficacy, pharmacokinetics, or toxicity. The chimeric peptide's stability in biological fluids and potential immunogenicity were not assessed. Manufacturing cost and scalability for stockpiling purposes were not addressed."},{"rthcId":"RPEP-03471","title":"Stress in Gastrointestinal Tract and Stable Gastric Pentadecapeptide BPC 157. Finally, do we have a Solution?","authors":"Sikiric, Predrag; Seiwerth, Sven; Rucman, Rudolf; Drmic, Domagoj; Stupnisek, Mirjana; Kokot, Antonio; Sever, Marko; Zoricic, Ivan; Zoricic, Zoran; Batelja, Lovorka; Ziger, Tihomil; Luetic, Kresimir; Vlainic, Josipa; Rasic, Zarko; Bencic, Martina Lovric","year":2017,"journal":"Current pharmaceutical design, 23(27), 4012-4028","doi":"10.2174/1381612823666170220163219","pmid":"28228068","tags":[],"studyType":"review","evidenceStrength":"low-moderate","keyFinding":"This comprehensive review from the primary BPC-157 research group presents BPC 157 (Body Protection Compound, a 15-amino-acid peptide derived from human gastric juice) as an integrative mediator of the body's stress response. The authors argue that BPC 157 counteracts a remarkably wide range of stress-induced damage across multiple organ systems: gastrointestinal tract, skin, tendons, ligaments, muscle, bone, nerve, cornea, and brain.\n\nKey proposed mechanisms include: promotion of angiogenesis (new blood vessel formation), interaction with the dopamine, serotonin, and GABA neurotransmitter systems, modulation of the nitric oxide (NO) system, and regulation of gene expression (Fos, c-Jun, Egr-1). The authors report that BPC 157 has shown no side effects in clinical trials and that a lethal dose (LD1) has not been reached in toxicity studies. They frame the peptide as stable in human gastric juice, making oral administration viable.","whyItMatters":"BPC-157 is one of the most discussed peptides in the performance and wellness community. This review from the group that discovered and most extensively studied the peptide provides the most comprehensive summary of their proposed mechanisms. If validated by independent research, BPC-157 could represent a novel approach to tissue healing and stress adaptation. However, the breadth of claimed benefits and the concentration of research within one group remain sources of scientific skepticism.","specificNumbers":"15-amino-acid peptide · Stable in human gastric juice · LD1 not achieved in toxicity studies · No side effects reported in clinical trials · Affects dopamine, serotonin, GABA, and NO systems · Gene regulation: Fos, c-Jun, Egr-1","methodology":"This is a narrative review authored by the primary BPC-157 research group, summarizing their body of work across multiple preclinical studies and limited clinical trials. It synthesizes findings from animal models of various organ injuries, neurotransmitter system studies, and gene expression analyses to build the case for BPC 157 as a master stress-response mediator.","limitations":"The vast majority of BPC-157 research comes from this single research group (Sikiric et al.), which limits independent verification. Most evidence is from animal models, with very limited human clinical data published. The extraordinarily broad range of claimed effects — healing virtually every tissue type and counteracting dozens of pathological conditions — is unusual for any single compound and raises scientific skepticism. The writing style and framing are advocacy-oriented rather than objectively critical."},{"rthcId":"RPEP-03472","title":"Acute oxytocin improves memory and gaze following in male but not female nursery-reared infant macaques.","authors":"Simpson, Elizabeth A; Paukner, Annika; Sclafani, Valentina; Kaburu, Stefano S K; Suomi, Stephen J; Ferrari, Pier F","year":2017,"journal":"Psychopharmacology, 234(3), 497-506","doi":"10.1007/s00213-016-4480-x","pmid":"27837331","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03473","title":"PanIN Neuroendocrine Cells Promote Tumorigenesis via Neuronal Cross-talk.","authors":"Sinha, Smrita; Fu, Ya-Yuan; Grimont, Adrien; Ketcham, Maren; Lafaro, Kelly; Saglimbeni, Joseph A; Askan, Gokce; Bailey, Jennifer M; Melchor, Jerry P; Zhong, Yi; Joo, Min Geol; Grbovic-Huezo, Olivera; Yang, In-Hong; Basturk, Olca; Baker, Lindsey; Park, Young; Kurtz, Robert C; Tuveson, David; Leach, Steven D; Pasricha, Pankaj J","year":2017,"journal":"Cancer research, 77(8), 1868-1879","doi":"10.1158/0008-5472.CAN-16-0899-T","pmid":"28386018","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03474","title":"Peptides semax and selank affect the behavior of rats with 6-OHDA induced PD-like parkinsonism.","authors":"Slominsky, P A; Shadrina, M I; Kolomin, T A; Stavrovskaya, A V; Filatova, E V; Andreeva, L A; Illarioshkin, S N; Myasoedov, N F","year":2017,"journal":"Doklady biological sciences : proceedings of the Academy of Sciences of the USSR, Biological sciences sections, 474(1), 106-109","doi":"10.1134/S0012496617030048","pmid":"28702721","tags":[],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"In rats with chemically induced Parkinson's-like symptoms, the peptide Selank (an analog of taftsin) reduced anxiety levels in the elevated plus maze test. Neither Selank nor Semax (an ACTH 4-10 fragment analog) affected motor activity or passive defensive behavior in the parkinsonian rats.\n\nNotably, Selank's anti-anxiety effect persisted even after toxic damage to the substantia nigra — the brain region destroyed in Parkinson's disease. This suggests Selank's anxiolytic mechanism operates independently of the dopaminergic neurons lost in parkinsonism, consistent with its previously demonstrated effects in healthy rodents under stress.","whyItMatters":"Parkinson's disease is primarily known for its motor symptoms, but anxiety and other neuropsychiatric symptoms affect up to 40% of PD patients and significantly reduce quality of life. Most anti-anxiety medications carry risks for PD patients. Finding that Selank's anti-anxiety effect survives even when dopamine neurons are destroyed suggests it could address non-motor PD symptoms through a separate mechanism.","specificNumbers":"6-OHDA lesion model · Elevated cross-shaped maze test · Selank reduced anxiety · No motor activity changes with either peptide · Semax (ACTH 4-10 analog) and Selank (taftsin analog) tested","methodology":"Researchers induced Parkinson's-like neurodegeneration in male rats using 6-hydroxydopamine (6-OHDA), which selectively destroys dopaminergic neurons in the substantia nigra. Rats were then treated with either Semax or Selank peptides. Behavior was assessed using the elevated plus maze (a standard test for anxiety) and passive defensive behavior paradigms.","limitations":"The 6-OHDA model mimics dopamine neuron loss but doesn't replicate the full complexity of human Parkinson's disease (which involves alpha-synuclein pathology and multiple neurotransmitter systems). The abstract doesn't report sample sizes, specific dosages, treatment duration, or statistical values. Published in a Russian Academy of Sciences proceedings journal with a brief format."},{"rthcId":"RPEP-03475","title":"A tetrameric peptide derived from bovine lactoferricin as a potential therapeutic tool for oral squamous cell carcinoma: A preclinical model.","authors":"Solarte, Víctor Alfonso; Conget, Paulette; Vernot, Jean-Paul; Rosas, Jaiver Eduardo; Rivera, Zuly Jenny; García, Javier Eduardo; Arango-Rodríguez, Martha Ligia","year":2017,"journal":"PloS one, 12(3), e0174707","doi":"10.1371/journal.pone.0174707","pmid":"28358840","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03476","title":"Identification of bacterial biofilm and the Staphylococcus aureus derived protease, staphopain, on the skin surface of patients with atopic dermatitis.","authors":"Sonesson, Andreas; Przybyszewska, Kornelia; Eriksson, Sigrid; Mörgelin, Matthias; Kjellström, Sven; Davies, Julia; Potempa, Jan; Schmidtchen, Artur","year":2017,"journal":"Scientific reports, 7(1), 8689","doi":"10.1038/s41598-017-08046-2","pmid":"28821865","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03477","title":"Aprepitant for refractory cutaneous T-cell lymphoma-associated pruritus: 4 cases and a review of the literature.","authors":"Song, Johanna S; Tawa, Marianne; Chau, Nicole G; Kupper, Thomas S; LeBoeuf, Nicole R","year":2017,"journal":"BMC cancer, 17(1), 200","doi":"10.1186/s12885-017-3194-8","pmid":"28302100","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03478","title":"The Role of Neurogenic Inflammation in Blood-Brain Barrier Disruption and Development of Cerebral Oedema Following Acute Central Nervous System (CNS) Injury.","authors":"Sorby-Adams, Annabel J; Marcoionni, Amanda M; Dempsey, Eden R; Woenig, Joshua A; Turner, Renée J","year":2017,"journal":"International journal of molecular sciences, 18(8)","doi":"10.3390/ijms18081788","pmid":"28817088","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03479","title":"Substance P-mediated chemokine production promotes monocyte migration.","authors":"Spitsin, Sergei; Meshki, John; Winters, Angela; Tuluc, Florin; Benton, Tami D; Douglas, Steven D","year":2017,"journal":"Journal of leukocyte biology, 101(4), 967-973","doi":"10.1189/jlb.1AB0416-188RR","pmid":"28366881","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03480","title":"Ghrelin, CCK, GLP-1, and PYY(3-36): Secretory Controls and Physiological Roles in Eating and Glycemia in Health, Obesity, and After RYGB.","authors":"Steinert, Robert E; Feinle-Bisset, Christine; Asarian, Lori; Horowitz, Michael; Beglinger, Christoph; Geary, Nori","year":2017,"journal":"Physiological reviews, 97(1), 411-463","doi":"10.1152/physrev.00031.2014","pmid":"28003328","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03481","title":"The Dynamics of Gastric Emptying and Self-Reported Feelings of Satiation Are Better Predictors Than Gastrointestinal Hormones of the Effects of Lipid Emulsion Structure on Fat Digestion in Healthy Adults-A Bayesian Inference Approach.","authors":"Steingoetter, Andreas; Buetikofer, Simon; Curcic, Jelena; Menne, Dieter; Rehfeld, Jens F; Fried, Michael; Schwizer, Werner; Wooster, Tim J","year":2017,"journal":"The Journal of nutrition, 147(4), 706-714","doi":"10.3945/jn.116.237800","pmid":"28228504","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03482","title":"Effects of cerebrolysin on nerve growth factor system in the aging rat brain.","authors":"Stepanichev, Mikhail; Onufriev, Mikhail; Aniol, Viktor; Freiman, Sofia; Brandstaetter, Hemma; Winter, Stefan; Lazareva, Natalia; Guekht, Alla; Gulyaeva, Natalia","year":2017,"journal":"Restorative neurology and neuroscience, 35(6), 571-581","doi":"10.3233/RNN-170724","pmid":"29172008","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03483","title":"Therapeutic design of peptide modulators of protein-protein interactions in membranes.","authors":"Stone, Tracy A; Deber, Charles M","year":2017,"journal":"Biochimica et biophysica acta. Biomembranes, 1859(4), 577-585","doi":"10.1016/j.bbamem.2016.08.013","pmid":"27580024","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03484","title":"BPC 157 counteracts QTc prolongation induced by haloperidol, fluphenazine, clozapine, olanzapine, quetiapine, sulpiride, and metoclopramide in rats.","authors":"Strinic, Dean; Belosic Halle, Zeljka; Luetic, Kresimir; Nedic, Ana; Petrovic, Igor; Sucic, Mario; Zivanovic Posilovic, Gordana; Balenovic, Dijana; Strbe, Sanja; Udovicic, Mario; Drmic, Domagoj; Stupnisek, Mirjana; Lovric Bencic, Martina; Seiwerth, Sven; Sikiric, Predrag","year":2017,"journal":"Life sciences, 186, 66-79","doi":"10.1016/j.lfs.2017.08.006","pmid":"28797793","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03485","title":"Alterations in Rat Accumbens Endocannabinoid and GABA Content during Fentanyl Treatment: The Role of Ghrelin.","authors":"Sustkova-Fiserova, Magdalena; Charalambous, Chrysostomos; Havlickova, Tereza; Lapka, Marek; Jerabek, Pavel; Puskina, Nina; Syslova, Kamila","year":2017,"journal":"International journal of molecular sciences, 18(11)","doi":"10.3390/ijms18112486","pmid":"29165386","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03486","title":"Role of Substance P Neuropeptide in Inflammation, Wound Healing, and Tissue Homeostasis.","authors":"Suvas, Susmit","year":2017,"journal":"Journal of immunology (Baltimore, Md. : 1950), 199(5), 1543-1552","doi":"10.4049/jimmunol.1601751","pmid":"28827386","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03487","title":"The mitochondrial-targeted peptide, SS-31, improves glomerular architecture in mice of advanced age.","authors":"Sweetwyne, Mariya T; Pippin, Jeffrey W; Eng, Diana G; Hudkins, Kelly L; Chiao, Ying Ann; Campbell, Matthew D; Marcinek, David J; Alpers, Charles E; Szeto, Hazel H; Rabinovitch, Peter S; Shankland, Stuart J","year":2017,"journal":"Kidney international, 91(5), 1126-1145","doi":"10.1016/j.kint.2016.10.036","pmid":"28063595","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03488","title":"\"Stress\" is 80 Years Old: From Hans Selye Original Paper in 1936 to Recent Advances in GI Ulceration.","authors":"Szabo, Sandor; Yoshida, Masashi; Filakovszky, Janos; Juhasz, Gyorgy","year":2017,"journal":"Current pharmaceutical design, 23(27), 4029-4041","doi":"10.2174/1381612823666170622110046","pmid":"28641541","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03489","title":"The Critical and Multifunctional Roles of Antimicrobial Peptides in Dermatology.","authors":"Takahashi, Toshiya; Gallo, Richard L","year":2017,"journal":"Dermatologic clinics, 35(1), 39-50","doi":"10.1016/j.det.2016.07.006","pmid":"27890236","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03490","title":"Chemical synthesis of membrane proteins by the removable backbone modification method.","authors":"Tang, Shan; Zuo, Chao; Huang, Dong-Liang; Cai, Xiao-Ying; Zhang, Long-Hua; Tian, Chang-Lin; Zheng, Ji-Shen; Liu, Lei","year":2017,"journal":"Nature protocols, 12(12), 2554-2569","doi":"10.1038/nprot.2017.129","pmid":"29189771","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03491","title":"SP and IL-33 together markedly enhance TNF synthesis and secretion from human mast cells mediated by the interaction of their receptors.","authors":"Taracanova, Alexandra; Alevizos, Mihail; Karagkouni, Anna; Weng, Zuiy; Norwitz, Errol; Conti, Pio; Leeman, Susan E; Theoharides, Theoharis C","year":2017,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 114(20), E4002-E4009","doi":"10.1073/pnas.1524845114","pmid":"28461492","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03492","title":"Treatment of Endometriosis-Associated Pain with Elagolix, an Oral GnRH Antagonist.","authors":"Taylor, Hugh S; Giudice, Linda C; Lessey, Bruce A; Abrao, Mauricio S; Kotarski, Jan; Archer, David F; Diamond, Michael P; Surrey, Eric; Johnson, Neil P; Watts, Nelson B; Gallagher, J Chris; Simon, James A; Carr, Bruce R; Dmowski, W Paul; Leyland, Nicholas; Rowan, Jean P; Duan, W Rachel; Ng, Juki; Schwefel, Brittany; Thomas, James W; Jain, Rita I; Chwalisz, Kristof","year":2017,"journal":"The New England journal of medicine, 377(1), 28-40","doi":"10.1056/NEJMoa1700089","pmid":"28525302","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03493","title":"Synthesis of 2-imino and 2-hydrazono thiazolo[4,5-d]pyrimidines as corticotropin releasing factor (CRF) antagonists.","authors":"Teleb, Mohamed; Kuppast, Bhimanna; Spyridaki, Katerina; Liapakis, George; Fahmy, Hesham","year":2017,"journal":"European journal of medicinal chemistry, 138, 900-908","doi":"10.1016/j.ejmech.2017.07.016","pmid":"28750312","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03494","title":"Elevated Postoperative Endogenous GLP-1 Levels Mediate Effects of Roux-en-Y Gastric Bypass on Neural Responsivity to Food Cues.","authors":"Ten Kulve, Jennifer S; Veltman, Dick J; Gerdes, Victor E A; van Bloemendaal, Liselotte; Barkhof, Frederik; Deacon, Carolyn F; Holst, Jens J; Drent, Madeleine L; Diamant, Michaela; IJzerman, Richard G","year":2017,"journal":"Diabetes care, 40(11), 1522-1529","doi":"10.2337/dc16-2113","pmid":"29025878","tags":["glp-1-receptor-agonists"],"studyType":"interventional","evidenceStrength":"preliminary","keyFinding":"After Roux-en-Y gastric bypass (RYGB), GLP-1 levels were significantly elevated, and brain responses to food cues were reduced in key reward and taste-processing regions. Using the GLP-1 receptor blocker exendin 9-39, the researchers demonstrated that blocking GLP-1 signaling reversed these brain changes — restoring the heightened food-cue responses that existed before surgery. This provides direct evidence that GLP-1 mediates the reduced food motivation seen after bariatric surgery.\n\nSpecifically, after RYGB, brain activation decreased in the rolandic operculum and caudate nucleus when viewing food pictures (P=0.03) and in the insula when tasting palatable food (P=0.003). Blocking GLP-1 receptors with exendin 9-39 reversed the reduced activation in the caudate nucleus (P=0.02) and insula (P=0.002).","whyItMatters":"This study helps explain why people lose so much weight after gastric bypass — it's not just about a smaller stomach. The surgery dramatically increases GLP-1 production, which changes how the brain responds to food. This is the same hormone that drugs like semaglutide and tirzepatide mimic, providing a biological explanation for why GLP-1 medications reduce food cravings in a similar way to bariatric surgery.","specificNumbers":"n=10 · GLP-1 levels significantly elevated post-RYGB · P=0.03 reduced brain activation to food pictures · P=0.003 reduced insula response to palatable food · P=0.02 and P=0.002 for GLP-1 blockade reversal effects","methodology":"Crossover study in 10 women before and after RYGB surgery. Each participant underwent functional MRI brain scans while viewing food pictures and tasting chocolate milk under two conditions: with exendin 9-39 (a GLP-1 receptor blocker) and with placebo. Comparing brain activation patterns across these conditions before and after surgery isolated the specific contribution of GLP-1 to post-surgical changes in food-related brain activity.","limitations":"Very small sample size of only 10 women limits generalizability. All-female cohort means results may not apply to men. The study design is complex with multiple comparisons, increasing the risk of false positive findings. Brain imaging studies capture neural activity but don't directly measure behavior or food intake. Short-term assessments may not reflect long-term effects."},{"rthcId":"RPEP-03495","title":"Topical Treatment of Rosacea with Ivermectin Inhibits Gene Expression of Cathelicidin Innate Immune Mediators, LL-37 and KLK5, in Reconstructed and Ex Vivo Skin Models.","authors":"Thibaut de Ménonville, Séverine; Rosignoli, Carine; Soares, Estelle; Roquet, Manon; Bertino, Béatrice; Chappuis, Jean-Paul; Defoin-Platel/Chaussade, Claire; Piwnica, David","year":2017,"journal":"Dermatology and therapy, 7(2), 213-225","doi":"10.1007/s13555-017-0176-3","pmid":"28243927","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Ivermectin inhibited KLK5 and CAMP (cathelicidin) gene expression and protein secretion in normal human epidermal keratinocytes (NHEK) stimulated with calcitriol. These results were confirmed in two 3D skin models — reconstructed human epidermis (RHE) and human skin ex vivo.\n\nThe anti-inflammatory effects extended beyond the cathelicidin pathway: ivermectin also reduced secretion of inflammatory cytokines IL-8, IL-6, and the chemokine MCP-1 (CCL2). This demonstrates that ivermectin targets the upstream molecular drivers of rosacea inflammation rather than just masking symptoms.","whyItMatters":"Rosacea affects millions of people and can significantly impact quality of life. Ivermectin cream is FDA-approved for rosacea but was originally an anti-parasitic drug — understanding that it works by modulating the antimicrobial peptide LL-37 provides a rational basis for its use and could inspire development of more targeted treatments that specifically address the cathelicidin/KLK5 pathway.","specificNumbers":"","methodology":"Three experimental systems were used: (1) normal human epidermal keratinocytes (NHEK) in 2D culture, (2) reconstructed human epidermis (RHE, a 3D skin model), and (3) human skin ex vivo. All models were stimulated with calcitriol (vitamin D3 metabolite) to induce KLK5 and LL-37 expression, mimicking rosacea conditions. Gene expression, protein secretion, and inflammatory cytokine levels were measured after ivermectin treatment.","limitations":"All experiments were performed in vitro or ex vivo — no clinical trial data are presented. The calcitriol stimulation model approximates but does not fully replicate the complex pathophysiology of rosacea in living patients. The study was funded by Nestlé Skin Health R&D (which markets ivermectin cream), representing a potential conflict of interest. Specific concentrations of ivermectin used are not detailed in the abstract."},{"rthcId":"RPEP-03496","title":"Neuropeptides and Addiction: An Introduction.","authors":"Thiele, Todd E","year":2017,"journal":"International review of neurobiology, 136, 1-3","doi":"10.1016/bs.irn.2017.07.001","pmid":"29056148","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03497","title":"Neuropeptide Y in Alcohol Addiction and Affective Disorders.","authors":"Thorsell, Annika; Mathé, Aleksander A","year":2017,"journal":"Frontiers in endocrinology, 8, 178","doi":"10.3389/fendo.2017.00178","pmid":"28824541","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03498","title":"Protective effects of agonists of growth hormone-releasing hormone (GHRH) in early experimental diabetic retinopathy.","authors":"Thounaojam, Menaka C; Powell, Folami L; Patel, Sagar; Gutsaeva, Diana R; Tawfik, Amany; Smith, Sylvia B; Nussbaum, Julian; Block, Norman L; Martin, Pamela M; Schally, Andrew V; Bartoli, Manuela","year":2017,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 114(50), 13248-13253","doi":"10.1073/pnas.1718592114","pmid":"29180438","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In streptozotocin-induced diabetic rats, treatment with the GHRH agonist MR-409 (15 μg/kg) prevented retinal morphological damage and particularly preserved retinal ganglion cell survival. MR-409 upregulated NRF-2-dependent antioxidant gene expression, downregulated pro-inflammatory cytokines and adhesion molecules, reduced VEGF expression while increasing PEDF expression, and decreased vascular permeability. GHRH and GHRH-R expression were significantly downregulated in both diabetic rat retinas and human diabetic retinas (postmortem). Treatment with the GHRH antagonist MIA-602 worsened retinal morphology, confirming that GHRH signaling is neuroprotective.","whyItMatters":"Current treatments for diabetic retinopathy (laser therapy, anti-VEGF injections) address late-stage disease. GHRH agonists could offer a new approach targeting early disease by simultaneously protecting neurons, reducing inflammation, fighting oxidative stress, and preventing vascular damage — addressing multiple pathological mechanisms with a single peptide-based therapy.","specificNumbers":"","methodology":"Researchers used streptozotocin-induced diabetic rats treated with the GHRH agonist MR-409 (15 μg/kg) or antagonist MIA-602. Retinal morphology was assessed histologically. Gene and protein expression were measured using qPCR and Western blotting for GHRH-R, inflammatory markers, oxidative stress pathways (NRF-2), and angiogenic factors (VEGF, PEDF). Vascular permeability was quantified. Human diabetic retinas (postmortem) were also analyzed for GHRH-R expression.","limitations":"This is a preclinical study in diabetic rats, and results may not directly translate to human diabetic retinopathy. The streptozotocin model mimics type 1 diabetes, while most diabetic retinopathy occurs in type 2 diabetes. The study examined early-stage retinopathy and did not assess whether MR-409 can reverse established disease. Long-term safety data for retinal use of GHRH agonists is lacking."},{"rthcId":"RPEP-03499","title":"Circulating cathelicidin levels correlate with mucosal disease activity in ulcerative colitis, risk of intestinal stricture in Crohn's disease, and clinical prognosis in inflammatory bowel disease.","authors":"Tran, Diana Hoang-Ngoc; Wang, Jiani; Ha, Christina; Ho, Wendy; Mattai, S Anjani; Oikonomopoulos, Angelos; Weiss, Guy; Lacey, Precious; Cheng, Michelle; Shieh, Christine; Mussatto, Caroline C; Ho, Samantha; Hommes, Daniel; Koon, Hon Wai","year":2017,"journal":"BMC gastroenterology, 17(1), 63","doi":"10.1186/s12876-017-0619-4","pmid":"28494754","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03500","title":"l-Theanine inhibits proinflammatory PKC/ERK/ICAM-1/IL-33 signaling, apoptosis, and autophagy formation in substance P-induced hyperactive bladder in rats.","authors":"Tsai, Wen-Hsin; Wu, Chung-Hsin; Yu, Hong-Jeng; Chien, Chiang-Ting","year":2017,"journal":"Neurourology and urodynamics, 36(2), 297-307","doi":"10.1002/nau.22965","pmid":"26828717","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03501","title":"Incretin-based pharmacotherapy and risk of adverse pancreatic events in the ethnic Chinese with diabetes mellitus: A population-based study in Taiwan.","authors":"Tseng, Chao-Ming; Liao, Wei-Chih; Chang, Chi-Yang; Lee, Ching-Tai; Tseng, Cheng-Hao; Hsu, Yao-Chun; Lin, Jaw-Town","year":2017,"journal":"Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.], 17(1), 76-82","doi":"10.1016/j.pan.2016.10.003","pmid":"27743712","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03502","title":"The correlation between central and peripheral oxytocin concentrations: A systematic review and meta-analysis.","authors":"Valstad, Mathias; Alvares, Gail A; Egknud, Maiken; Matziorinis, Anna Maria; Andreassen, Ole A; Westlye, Lars T; Quintana, Daniel S","year":2017,"journal":"Neuroscience and biobehavioral reviews, 78, 117-124","doi":"10.1016/j.neubiorev.2017.04.017","pmid":"28442403","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Meta-analysis of 17 studies with 516 total participants/subjects found:\n\n- Overall central-peripheral oxytocin correlation: r=0.29 (95% CI: 0.14-0.42, p=0.003)\n- Under basal (resting) conditions: r=0.08 (p=0.31) — NO significant correlation\n- After intranasal oxytocin administration: r=0.66 (p<0.0001) — STRONG correlation\n- After experimentally induced stress: r=0.49 (p=0.001) — MODERATE correlation\n\nThese results indicate that central and peripheral oxytocin release are coordinated after stress or exogenous administration, but not under resting conditions. The common research practice of using blood oxytocin to approximate brain oxytocin at baseline is not supported.","whyItMatters":"Oxytocin is being investigated as a treatment for autism, social anxiety, PTSD, and other psychiatric conditions. Many clinical studies measure blood oxytocin as a biomarker, but this meta-analysis shows that resting blood levels don't tell us what's happening in the brain — potentially invalidating the conclusions of studies that relied on this assumption.","specificNumbers":"","methodology":"Pre-registered systematic search and meta-analysis. Databases were searched for studies reporting both central (cerebrospinal fluid) and peripheral (blood/plasma/saliva) oxytocin concentrations in the same subjects. 17 studies with 516 participants/subjects were included. Correlations were calculated overall and stratified by condition (basal, post-intranasal administration, post-stress).","limitations":"The meta-analysis included only 17 studies with a combined 516 subjects, which is relatively modest. Many included studies used animal subjects, and results may not fully translate to human clinical populations. Central oxytocin measurement requires cerebrospinal fluid collection, which limits the types of studies that can be done. Different peripheral measurement methods (plasma, saliva, urine) may have different correlations."},{"rthcId":"RPEP-03503","title":"Small intestinal protein infusion in humans: evidence for a location-specific gradient in intestinal feedback on food intake and GI peptide release.","authors":"van Avesaat, M; Ripken, D; Hendriks, H F J; Masclee, A A M; Troost, F J","year":2017,"journal":"International journal of obesity (2005), 41(2), 217-224","doi":"10.1038/ijo.2016.196","pmid":"27811949","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03504","title":"Antibacterial Synthetic Peptides Derived from Bovine Lactoferricin Exhibit Cytotoxic Effect against MDA-MB-468 and MDA-MB-231 Breast Cancer Cell Lines.","authors":"Vargas Casanova, Yerly; Rodríguez Guerra, Jorge Antonio; Umaña Pérez, Yadi Adriana; Leal Castro, Aura Lucía; Almanzar Reina, Giovanni; García Castañeda, Javier Eduardo; Rivera Monroy, Zuly Jenny","year":2017,"journal":"Molecules (Basel, Switzerland), 22(10)","doi":"10.3390/molecules22101641","pmid":"28961215","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03505","title":"Marine Fish Proteins and Peptides for Cosmeceuticals: A Review.","authors":"Venkatesan, Jayachandran; Anil, Sukumaran; Kim, Se-Kwon; Shim, Min Suk","year":2017,"journal":"Marine drugs, 15(5)","doi":"10.3390/md15050143","pmid":"28524092","tags":["cosmetic-and-skin-peptides","collagen-peptides"],"studyType":"narrative-review","evidenceStrength":"low","keyFinding":"Marine fish-derived proteins and peptides — particularly those obtained from enzymatic hydrolysis of fish processing by-products — show a broad range of activities relevant to skincare: antioxidant, antimicrobial, anti-aging, anti-photoaging, and matrix metalloproteinase (MMP) inhibition. Fish-derived collagen specifically demonstrates abilities in skin repair and tissue regeneration.\n\nThe review highlights that these peptides are increasingly being developed into cosmeceutical products, taking advantage of both their bioactivity and the sustainability angle of using fish processing waste as the raw material.","whyItMatters":"The cosmeceutical industry is rapidly adopting marine-derived peptides as alternatives to synthetic ingredients. Fish collagen peptides are particularly appealing because they're biocompatible, can be sourced sustainably from processing waste, and avoid the religious and cultural concerns associated with bovine or porcine collagen. This review maps the landscape of what's available and what activities have been demonstrated.","specificNumbers":"Review paper · Covers antioxidant, antimicrobial, anti-aging, anti-photoaging activities · MMP inhibition demonstrated · Fish collagen for tissue regeneration · Chemical + enzymatic hydrolysis methods","methodology":"Narrative review synthesizing published literature on marine fish-derived proteins and peptides, covering isolation methods (chemical and enzymatic hydrolysis), bioactive properties, and cosmeceutical applications.","limitations":"Narrative review without systematic methodology. Most evidence cited is from in vitro or preclinical studies. Clinical evidence for cosmeceutical efficacy in humans is limited. The review does not critically assess study quality or provide effect size comparisons. Bioavailability and penetration through human skin are not deeply addressed."},{"rthcId":"RPEP-03506","title":"Exendin-4 Treatment Improves LPS-Induced Depressive-Like Behavior Without Affecting Pro-Inflammatory Cytokines.","authors":"Ventorp, Filip; Bay-Richter, Cecilie; Nagendra, Analise Sauro; Janelidze, Shorena; Matsson, Viktor Sjödahl; Lipton, Jack; Nordström, Ulrika; Westrin, Åsa; Brundin, Patrik; Brundin, Lena","year":2017,"journal":"Journal of Parkinson's disease, 7(2), 263-273","doi":"10.3233/JPD-171068","pmid":"28387682","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03507","title":"Periprosthetic UHMWPE Wear Debris Induces Inflammation, Vascularization, and Innervation After Total Disc Replacement in the Lumbar Spine.","authors":"Veruva, Sai Y; Lanman, Todd H; Isaza, Jorge E; Freeman, Theresa A; Kurtz, Steven M; Steinbeck, Marla J","year":2017,"journal":"Clinical orthopaedics and related research, 475(5), 1369-1381","doi":"10.1007/s11999-016-4996-8","pmid":"27488379","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Compared to normal disc tissue, TDR periprosthetic tissue showed dramatically elevated TNFα (5.17 vs 0.05, p=0.02), VEGF (3.02 vs 0.02, p=0.02), and substance P (4.15 vs 0.08, p=0.02). Even compared to painful degenerative disc disease tissue, TDR tissue had higher IL-1β (p=0.01), VEGF (p=0.04), and substance P (p=0.01).\n\nFive factors (TNFα, IL-1β, VEGF, NGF, substance P) strongly correlated with wear particle number, macrophage count, and blood vessel density. Key correlations: TNFα with wear particles (p<0.001, ρ=0.63), VEGF with macrophages (p=0.001, ρ=0.71), and NGF with blood vessels (p<0.001, ρ=0.70). PDGFbb, NGF, and substance P expression localized predominantly to blood vessels and nerve fibers.","whyItMatters":"Understanding why disc replacements cause pain in some patients is critical for improving implant design and developing treatments that could prevent revision surgery. This study identifies substance P and NGF as key players in a cascade where wear debris drives inflammation, new blood vessel growth, and nerve sprouting around implants — creating pain circuits that didn't exist before surgery.","specificNumbers":"","methodology":"Periprosthetic tissues from 11 patients with TDRs revised for pain (mean implantation 3 years, range 1-6) were analyzed. Controls included tissue from 4 patients with painful degenerative disc disease and 3 normal autopsy specimens. Wear particles were quantified by polarized light microscopy. Immunohistochemistry identified TNFα, IL-1β, VEGF, PDGFbb, NGF, substance P, macrophages, and blood vessels. Quantification used MATLAB and ImageJ with threshold-based analysis.","limitations":"Small sample size (11 TDR patients, 4 degenerative disc disease, 3 normal controls) limits statistical power. The study examined tissue at revision surgery, so it captures only severe cases that required reoperation. The correlation data cannot establish causation. Different implant designs and polyethylene types may produce different amounts of wear debris."},{"rthcId":"RPEP-03508","title":"Oral Treatment with the Ghrelin Receptor Agonist HM01 Attenuates Cachexia in Mice Bearing Colon-26 (C26) Tumors.","authors":"Villars, Fabienne O; Pietra, Claudio; Giuliano, Claudio; Lutz, Thomas A; Riediger, Thomas","year":2017,"journal":"International journal of molecular sciences, 18(5)","doi":"10.3390/ijms18050986","pmid":"28475119","tags":["ghrelin","cancer-cachexia"],"studyType":"Animal Study","evidenceStrength":"Low-Moderate","keyFinding":"An oral ghrelin receptor agonist called HM01 significantly reduced cancer-related wasting (cachexia) in mice with colon tumors. Treated mice had increased food intake, body weight, fat mass, muscle mass, and bone mineral density, while energy expenditure decreased. Notably, these benefits occurred even though HM01 did not reduce the inflammatory cytokines (IL-6 and MIC-1) or muscle degradation markers (MuRF-1 and MAFbx) that drive cachexia. This suggests HM01 works by boosting caloric intake and reducing energy burning rather than blocking the inflammatory wasting pathways directly.\n\nThe study also mapped the timeline of cachexia progression: the inflammatory cytokine MIC-1 rose first, followed by IL-6, and muscle degradation markers increased last.","whyItMatters":"Cancer cachexia — the severe muscle and weight loss that accompanies many cancers — affects up to 80% of advanced cancer patients and directly contributes to death. There are currently no approved drugs that effectively treat it. The fact that an oral ghrelin agonist could preserve muscle and bone mass in this model, without needing to block the underlying inflammatory cascade, opens up a practical treatment strategy that could work alongside anti-cancer therapies.","specificNumbers":"","methodology":"Researchers inoculated mice with colon-26 tumor cells to induce cancer cachexia, then treated them orally with HM01, a non-peptide ghrelin receptor agonist. They tracked body weight, body composition (fat and lean mass via DEXA-like scanning), bone mineral density, food intake, and energy expenditure over the course of tumor development. They also measured inflammatory cytokines (IL-6 and MIC-1) and muscle degradation markers (MuRF-1 and MAFbx) to understand the mechanism.","limitations":"This is a mouse study using a single tumor model (colon-26), so results may not translate to humans or other cancer types. The C26 model produces cachexia without severe anorexia, which may not represent all forms of cancer cachexia. HM01 is a non-peptide small molecule rather than a peptide itself, though it acts on the ghrelin peptide pathway. No long-term survival data were reported."},{"rthcId":"RPEP-03509","title":"Nonsteroidal anti-inflammatory drugs-induced failure of lower esophageal and pyloric sphincter and counteraction of sphincters failure with stable gatric pentadecapeptide BPC 157 in rats.","authors":"Vitaic, S; Stupnisek, M; Drmic, D; Bauk, L; Kokot, A; Klicek, R; Vcev, A; Luetic, K; Seiwerth, S; Sikiric, P","year":2017,"journal":"Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 68(2), 265-272","doi":null,"pmid":"28614776","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"All five tested NSAIDs — diclofenac, ibuprofen, paracetamol, aspirin, and celecoxib — caused rapid and persistent drops in both lower esophageal sphincter and pyloric sphincter pressure in rats. BPC-157, given at doses of 10 μg/kg or 10 ng/kg, minimized the initial pressure drop and restored sphincter pressures to normal values in all NSAID groups.\n\nThe peptide was effective regardless of administration route (intraperitoneal injection, intragastric administration, or dissolved in drinking water) and worked against both traditional NSAIDs and the COX-2 selective inhibitor celecoxib. This consistent counteraction across multiple NSAIDs and routes suggests a robust protective mechanism.","whyItMatters":"NSAIDs are among the most widely used drugs worldwide, and their gastrointestinal side effects — including sphincter dysfunction leading to acid reflux — affect millions of people. Current protective strategies (proton pump inhibitors) address acid but not sphincter function. A peptide that directly restores sphincter competence could represent an entirely new approach to preventing NSAID-related digestive complications.","specificNumbers":"","methodology":"Wistar rats were treated with various NSAID regimens known to produce gastrointestinal damage: diclofenac (12.5 and 40 mg/kg IP), ibuprofen (400 mg/day/kg IP for 4 weeks), paracetamol (5.0 g/kg IP), aspirin (400 mg/kg IP or intragastric), and celecoxib (0.5 and 1.0 mg/kg IP). Lower esophageal and pyloric sphincter pressures were measured in cmH₂O. BPC-157 (10 μg/kg or 10 ng/kg) was given immediately after NSAIDs via injection, intragastrically, or in drinking water.","limitations":"This is entirely an animal study in Wistar rats — no human data on BPC-157's effects on sphincter function exist. The study comes from a single research group (Sikiric laboratory in Zagreb) that has published the majority of BPC-157 literature, and independent replication is limited. Specific statistical analyses and group sizes were not detailed in the abstract. The clinical relevance of the pressure measurements to human symptomatology (e.g., reflux, gastroparesis) is not established."},{"rthcId":"RPEP-03510","title":"Heterozygosity for the rs696217 SNP in the Preproghrelin Gene Predicts Weight Loss After Bariatric Surgery in Severely Obese Individuals.","authors":"Vitolo, Edoardo; Santini, Eleonora; Seghieri, Marta; Giannini, Livia; Coppedè, Fabio; Rossi, Chiara; Dardano, Angela; Solini, Anna","year":2017,"journal":"Obesity surgery, 27(4), 961-967","doi":"10.1007/s11695-016-2387-6","pmid":"27681093","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Patients heterozygous for the rs696217 SNP (GT genotype) in the preproghrelin gene achieved 38.1% BMI reduction at 52 weeks post-surgery, compared to 30.5% for GG homozygotes (p<0.001). Carrying the rs1126535 C allele in the CD40L gene was associated with lower BMI reduction at 52 weeks (28.1% vs 33.2%, p=0.049). Variants in the ghrelin receptor (rs490683), another preproghrelin SNP (rs27647), and adiponectin gene (rs2241766) showed no significant association with weight loss outcomes.","whyItMatters":"Bariatric surgery is a major intervention with variable outcomes, and predicting who will benefit most could improve patient selection and counseling. The ghrelin system is central to appetite regulation, and knowing that a genetic variant in the ghrelin gene predicts better surgical outcomes strengthens the case for personalized medicine in obesity treatment. It also reinforces ghrelin's importance as a therapeutic target.","specificNumbers":"","methodology":"Prospective cohort study of 100 otherwise healthy obese patients (mean age 45, 65% female, mean BMI 48.0 kg/m²) who underwent Roux-en-Y gastric bypass between 2014-2015. Five SNPs in genes encoding ghrelin, ghrelin receptor, adiponectin, and CD40L were genotyped from circulating lymphomonocyte DNA. Patients were followed at 6, 26, and 52 weeks post-surgery, with 79 completing the 52-week follow-up.","limitations":"The sample size of 100 patients is modest, with only 79 completing 52-week follow-up. The CD40L finding (p=0.049) is borderline significant and may not replicate. The study tested only a limited panel of SNPs — other genetic variants may contribute to weight loss outcomes. Single-center design limits generalizability. The mechanism by which rs696217 influences post-surgical weight loss was not investigated. Follow-up was limited to one year."},{"rthcId":"RPEP-03511","title":"Appetite regulating factors in pacu (Piaractus mesopotamicus): Tissue distribution and effects of food quantity and quality on gene expression.","authors":"Volkoff, Hélène; Estevan Sabioni, Rafael; Coutinho, Luiz Lehmann; Cyrino, José Eurico Possebon","year":2017,"journal":"Comparative biochemistry and physiology. Part A, Molecular & integrative physiology, 203, 241-254","doi":"10.1016/j.cbpa.2016.09.022","pmid":"27717774","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03512","title":"Substance P increases liver fibrosis by differential changes in senescence of cholangiocytes and hepatic stellate cells.","authors":"Wan, Ying; Meng, Fanyin; Wu, Nan; Zhou, Tianhao; Venter, Julie; Francis, Heather; Kennedy, Lindsey; Glaser, Trenton; Bernuzzi, Francesca; Invernizzi, Pietro; Glaser, Shannon; Huang, Qiaobing; Alpini, Gianfranco","year":2017,"journal":"Hepatology (Baltimore, Md.), 66(2), 528-541","doi":"10.1002/hep.29138","pmid":"28256736","tags":[],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Substance P drives liver fibrosis during cholestatic liver injury by acting through the neurokinin-1 receptor (NK-1R). Knocking out NK-1R in mice or blocking it with the antagonist L-733,060 significantly reduced liver fibrosis, as shown by decreased sirius red staining, lower fibrosis gene expression, and reduced TGF-β1 levels in serum.\n\nThe mechanism involves a dual effect on cellular senescence: Substance P decreases senescence in hepatic stellate cells (keeping them active and fibrosis-promoting) while increasing senescence in cholangiocytes (bile duct cells). Blocking NK-1R reversed both of these effects. Human tissue from primary sclerosing cholangitis patients also showed elevated expression of Substance P and NK-1R compared to healthy controls.","whyItMatters":"Liver fibrosis is a major driver of chronic liver disease progression, and current treatments are limited. This study identifies the Substance P/NK-1R signaling pathway as a potential therapeutic target — and an NK-1R antagonist (L-733,060) already reduced fibrosis in two different mouse models. The fact that human liver tissue from primary sclerosing cholangitis patients showed the same elevated SP/NK-1R expression suggests this pathway is clinically relevant.","specificNumbers":"NK-1R knockout reduced BDL-induced fibrosis · L-733,060 reduced fibrosis in Mdr2−/− mice · decreased sirius red staining · reduced TGF-β1 levels · elevated SP/NK-1R in human PSC tissue","methodology":"Researchers used multiple mouse models: wild-type and NK-1R knockout mice that underwent bile duct ligation (BDL) or sham surgery, and Mdr2 knockout mice treated with either the NK-1R antagonist L-733,060 or saline. Wild-type mice were also treated with Substance P or saline. Liver fibrosis was measured by sirius red staining, fibrosis gene/protein expression, and TGF-β1 levels. Cellular senescence was assessed in hepatic stellate cells and cholangiocytes. Human liver tissue from primary sclerosing cholangitis patients was also analyzed.","limitations":"This is primarily an animal study using mouse models, so results may not fully translate to human liver disease. While human PSC tissue showed elevated SP/NK-1R expression, no therapeutic interventions were tested in human subjects. The NK-1R antagonist L-733,060 has not been evaluated in clinical trials for liver fibrosis."},{"rthcId":"RPEP-03513","title":"Immunopotentiator Thymosin Alpha-1 Promotes Neurogenesis and Cognition in the Developing Mouse via a Systemic Th1 Bias.","authors":"Wang, Ge; He, Fen; Xu, Yunlong; Zhang, Yuwei; Wang, Xiao; Zhou, Chunhua; Huang, Yihong; Zou, Juntao","year":2017,"journal":"Neuroscience bulletin, 33(6), 675-684","doi":"10.1007/s12264-017-0162-x","pmid":"28780644","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03514","title":"The role of substance P in epilepsy and seizure disorders.","authors":"Wang, Xue Feng; Ge, Tong Tong; Fan, Jie; Yang, Wei; Cui, Ran Ji","year":2017,"journal":"Oncotarget, 8(44), 78225-78233","doi":"10.18632/oncotarget.20606","pmid":"29100462","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03515","title":"Pain in knee osteoarthritis is associated with variation in the neurokinin 1/substance P receptor (TACR1) gene.","authors":"Warner, S C; Walsh, D A; Laslett, L L; Maciewicz, R A; Soni, A; Hart, D J; Zhang, W; Muir, K R; Dennison, E M; Leaverton, P; Rampersaud, E; Cooper, C; Spector, T D; Cicuttini, F M; Arden, N K; Jones, G; Doherty, M; Valdes, A M","year":2017,"journal":"European journal of pain (London, England), 21(7), 1277-1284","doi":"10.1002/ejp.1027","pmid":"28493529","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03516","title":"Oxytocin receptor gene variations predict neural and behavioral response to oxytocin in autism.","authors":"Watanabe, Takamitsu; Otowa, Takeshi; Abe, Osamu; Kuwabara, Hitoshi; Aoki, Yuta; Natsubori, Tatsunobu; Takao, Hidemasa; Kakiuchi, Chihiro; Kondo, Kenji; Ikeda, Masashi; Iwata, Nakao; Kasai, Kiyoto; Sasaki, Tsukasa; Yamasue, Hidenori","year":2017,"journal":"Social cognitive and affective neuroscience, 12(3), 496-506","doi":"10.1093/scan/nsw150","pmid":"27798253","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03517","title":"Overcoming the Lack of Oral Availability of Cyclic Hexapeptides: Design of a Selective and Orally Available Ligand for the Integrin αvβ3.","authors":"Weinmüller, Michael; Rechenmacher, Florian; Kiran Marelli, Udaya; Reichart, Florian; Kapp, Tobias G; Räder, Andreas F B; Di Leva, Francesco Saverio; Marinelli, Luciana; Novellino, Ettore; Muñoz-Félix, José M; Hodivala-Dilke, Kairbaan; Schumacher, Adi; Fanous, Joseph; Gilon, Chaim; Hoffman, Amnon; Kessler, Horst","year":2017,"journal":"Angewandte Chemie (International ed. in English), 56(51), 16405-16409","doi":"10.1002/anie.201709709","pmid":"29072809","tags":["oral-peptides","peptide-engineering","drug-design"],"studyType":"Basic Science (Peptide Chemistry + Animal Proof of Concept)","evidenceStrength":"Moderate","keyFinding":"Researchers developed a systematic method to create cyclic peptides that can be taken orally — solving one of the biggest challenges in peptide drug development. Their approach combined two strategies: (1) N-methylation of the peptide backbone to improve intestinal permeability, and (2) protecting charged groups with lipophilic prodrug modifications to allow absorption.\n\nThey applied this to create an orally bioavailable RGD-containing hexapeptide that selectively binds the integrin αvβ3 — a receptor involved in tumor blood vessel growth. The final compound showed biological effects in mice after oral administration, proving the concept works in a living organism. The method involved screening combinatorial libraries for permeability, then systematically optimizing for receptor selectivity and oral absorption.","whyItMatters":"Most peptide drugs must be injected because they're destroyed in the stomach or can't cross the intestinal wall. Making peptides orally bioavailable would transform the field — imagine taking semaglutide as a simple pill instead of a weekly injection. This study provides a generalizable design framework: cyclize the peptide, selectively N-methylate the backbone, then add prodrug protecting groups. While the specific target here is cancer-related integrins, the methodology could be applied to make many other peptide drugs orally available.","specificNumbers":"6-amino acid cyclic peptide · systematic N-methylation library screening · RGD sequence for integrin binding · selective for αvβ3 · oral activity confirmed in mice · published in Angewandte Chemie","methodology":"Seven-step systematic approach: (1) designed a combinatorial library of N-methylated cyclic hexapeptide analogs, (2) selected peptides with highest intestinal permeability, (3) designed sublibraries incorporating the bioactive RGD sequence in all possible positions, (4) selected best integrin αvβ3 ligands, (5) fine-tuned affinity and selectivity via additional amino acid substitutions, (6) applied lipophilic prodrug protecting groups to restore oral permeability, (7) demonstrated biological activity in mice after oral dosing.","limitations":"The method was demonstrated for cyclic hexapeptides targeting one specific receptor — it remains to be seen how broadly this approach generalizes to other peptide targets and sizes. The prodrug protecting groups must be cleaved in vivo to release the active peptide, and this conversion efficiency may vary. The mouse proof-of-concept does not establish therapeutic efficacy or safety. Manufacturing complexity of N-methylated cyclic prodrug peptides could be a barrier to clinical development."},{"rthcId":"RPEP-03518","title":"Clinical Safety of Bariatric Arterial Embolization: Preliminary Results of the BEAT Obesity Trial.","authors":"Weiss, Clifford R; Akinwande, Olaguoke; Paudel, Kaylan; Cheskin, Lawrence J; Holly, Brian; Hong, Kelvin; Fischman, Aaron M; Patel, Rahul S; Shin, Eun J; Steele, Kimberley E; Moran, Timothy H; Kaiser, Kristen; Park, Amie; Shade, David M; Kraitchman, Dara L; Arepally, Aravind","year":2017,"journal":"Radiology, 283(2), 598-608","doi":"10.1148/radiol.2016160914","pmid":"28195823","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03519","title":"Synthesis of a Bifunctional Peptide Inhibitor-IgG1 Fc Fusion That Suppresses Experimental Autoimmune Encephalomyelitis.","authors":"White, Derek R; Khedri, Zahra; Kiptoo, Paul; Siahaan, Teruna J; Tolbert, Thomas J","year":2017,"journal":"Bioconjugate chemistry, 28(7), 1867-1877","doi":"10.1021/acs.bioconjchem.7b00175","pmid":"28581731","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03520","title":"Usefulness of ambulatory blood pressure monitoring to assess the melanocortin receptor agonist bremelanotide.","authors":"White, William B; Myers, Martin G; Jordan, Robert; Lucas, Johna","year":2017,"journal":"Journal of hypertension, 35(4), 761-768","doi":"10.1097/HJH.0000000000001221","pmid":"27977473","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03521","title":"The renal and cardiovascular effects of natriuretic peptides.","authors":"Wong, Philip Ching Yat; Guo, Jun; Zhang, Aidong","year":2017,"journal":"Advances in physiology education, 41(2), 179-185","doi":"10.1152/advan.00177.2016","pmid":"28377431","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03522","title":"Growth hormone-releasing hormone antagonist inhibits the invasiveness of human endometrial cancer cells by down-regulating twist and N-cadherin expression.","authors":"Wu, Hsien-Ming; Huang, Hong-Yuan; Schally, Andrew V; Chao, Angel; Chou, Hung-Hsueh; Leung, Peter C K; Wang, Hsin-Shih","year":2017,"journal":"Oncotarget, 8(3), 4410-4421","doi":"10.18632/oncotarget.13877","pmid":"28032599","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A growth hormone-releasing hormone (GHRH) antagonist inhibited the invasion and migration of endometrial cancer cells in a dose-dependent manner. The mechanism involved suppression of Twist and N-cadherin — two proteins critical for cancer cell motility and the epithelial-to-mesenchymal transition. When the GHRH receptor was knocked down using siRNA, the antagonist's suppressive effects were abolished, confirming the action is mediated specifically through the GHRH receptor. Similarly, independently silencing Twist or N-cadherin each suppressed cell motility, validating these as key downstream targets.","whyItMatters":"Over 25% of endometrial cancer patients present with invasive disease and metastases. This study identifies a new mechanism by which GHRH antagonists — peptide-based compounds — could combat cancer spread by targeting the molecular machinery of cell invasion, potentially opening a new therapeutic approach for endometrial cancer.","specificNumbers":"Dose-dependent inhibition of cell motility · Twist and N-cadherin suppressed · GHRH receptor siRNA abolished effect · >25% of endometrial cancer patients have invasive disease","methodology":"In vitro laboratory study using human endometrial cancer cell lines. GHRH receptor expression was confirmed by Western blotting and immunohistochemistry. Cancer cell invasion and migration were measured using motility assays after treatment with GHRH antagonist at varying doses. Gene silencing with siRNA was used to knock down the GHRH receptor, Twist, and N-cadherin individually to confirm the signaling pathway.","limitations":"This is an in vitro cell line study, so the findings may not translate directly to human tumors in vivo. No animal models or clinical data were presented. The specific GHRH antagonist used and its dosing are described in relative terms (dose-dependent) without absolute concentrations mentioned in the abstract. The study did not assess effects on normal endometrial cells."},{"rthcId":"RPEP-03523","title":"Real-time near-infrared bioimaging of a receptor-targeted cytotoxic dendritic theranostic agent.","authors":"Wu, Junchen; Zhou, Yuren; Li, Shang; Qu, Dahui; Zhu, Wei-Hong; Tian, He","year":2017,"journal":"Biomaterials, 120, 1-10","doi":"10.1016/j.biomaterials.2016.11.011","pmid":"28011190","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The dendritic theranostic agent P-FU 4, which combines Substance P targeting with four 5-FU drug molecules and a near-infrared imaging dye, demonstrated several key outcomes: 16% drug loading capacity, dose-dependent cytotoxicity against cancer cells with minimal effect on normal cells, preferential uptake by tumor cells through NK1R-mediated interaction, and 60.2% tumor inhibition rate in a mouse model.\n\nThe nanoparticle self-assembled from the dendritic construct, and the dendron architecture prevented the fluorescent dye from aggregation-mediated quenching, maintaining strong near-infrared signal for real-time monitoring of drug distribution.","whyItMatters":"A major challenge in chemotherapy is getting drugs to tumors without damaging healthy tissue. By using the neuropeptide Substance P as a guided missile to seek out NK1 receptors on tumor cells, this approach delivers drugs more precisely. The built-in imaging capability allows doctors to see where the drug accumulates in real time, combining diagnosis and treatment in a single platform.","specificNumbers":"","methodology":"Researchers designed a dendritic molecular construct using lysine branch points to conjugate four 5-FU molecules, Substance P (as the tumor-targeting ligand), and a near-infrared squaraine dye onto a single platform. The construct self-assembled into nanoparticles. In vitro cytotoxicity was tested against cancer and normal cell lines. In vivo studies used a mouse tumor model (BALB/c nude mice) to assess tumor inhibition and near-infrared fluorescence imaging.","limitations":"The 60.2% tumor inhibition rate, while significant, means substantial tumor growth continued. The study used nude mouse xenograft models, which lack normal immune function and may not predict human responses. Long-term toxicity, pharmacokinetics, and biodistribution were not fully characterized. NK1R expression varies across tumor types, limiting this approach to NK1R-positive cancers. Scale-up manufacturing of the complex dendritic construct could be challenging."},{"rthcId":"RPEP-03524","title":"Preparation of Antioxidant Peptides from Salmon Byproducts with Bacterial Extracellular Proteases.","authors":"Wu, Ribang; Chen, Leilei; Liu, Dan; Huang, Jiafeng; Zhang, Jiang; Xiao, Xiao; Lei, Ming; Chen, Yuelin; He, Hailun","year":2017,"journal":"Marine drugs, 15(1)","doi":"10.3390/md15010004","pmid":"28085023","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Salmon muscle proteins digested with Pseudoalteromonas sp. SQN1 crude enzymes produced the strongest antioxidant hydrolysate: 74.06% DPPH radical scavenging and 69.71% hydroxyl radical scavenging. Collagen was easier to degrade but produced weaker antioxidants.\n\nThe purified fraction U2-S2-I showed strong antioxidant activity:\n- DPPH scavenging IC50: 0.263 mg/mL\n- Hydroxyl radical scavenging IC50: 0.512 mg/mL\n- Oxygen radical absorption capacity: 1.960 mmol Trolox equivalent/g\n- Protected plasmid DNA from hydroxyl radical damage at levels comparable to the original hydrolysate, indicating it contained the primary bioactive peptides.","whyItMatters":"Fish processing waste is a significant environmental and economic problem. Converting this waste into bioactive antioxidant peptides adds value to byproducts that would otherwise be discarded, while producing ingredients for functional foods, nutraceuticals, or cosmetics. Using bacterial enzymes — especially from marine bacteria adapted to marine substrates — provides a sustainable and efficient approach to this bioconversion.","specificNumbers":"","methodology":"Extracellular proteases from 6 marine and 7 terrestrial bacterial strains were prepared through fermentation. Enzyme profiles were analyzed by substrate-immersing zymography. These proteases hydrolyzed salmon skin collagen and muscle proteins separately. Antioxidant activity was measured by DPPH and hydroxyl radical scavenging assays and Fe2+ chelating assay. The best hydrolysate was purified through ultrafiltration, cation exchange chromatography, and size exclusion chromatography. The purified fraction was tested for DNA protection.","limitations":"All results are in vitro — antioxidant activity in test tubes may not translate to health benefits in humans. The specific peptide sequences responsible for the antioxidant activity were not identified. Gastrointestinal stability and bioavailability of these peptides were not assessed. The bacterial enzyme preparation is crude and would require standardization for industrial use. Only one fish species (salmon) was tested."},{"rthcId":"RPEP-03525","title":"Isolation and identification of calcium-chelating peptides from Pacific cod skin gelatin and their binding properties with calcium.","authors":"Wu, Wenfei; Li, Bafang; Hou, Hu; Zhang, Hongwei; Zhao, Xue","year":2017,"journal":"Food & function, 8(12), 4441-4448","doi":"10.1039/c7fo01014a","pmid":"29090707","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03526","title":"Synergistic effects of antimicrobial peptide DP7 combined with antibiotics against multidrug-resistant bacteria.","authors":"Wu, Xiaozhe; Li, Zhan; Li, Xiaolu; Tian, Yaomei; Fan, Yingzi; Yu, Chaoheng; Zhou, Bailing; Liu, Yi; Xiang, Rong; Yang, Li","year":2017,"journal":"Drug design, development and therapy, 11, 939-946","doi":"10.2147/DDDT.S107195","pmid":"28356719","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"DP7 demonstrated potent antimicrobial activity on its own against all tested clinical isolates, with minimum inhibitory concentrations at or below 32 mg/L. When combined with vancomycin or azithromycin, the effects were frequently synergistic rather than merely additive. Notably, the synergy between DP7 and azithromycin was strongest against the most resistant strains — those carrying two or more azithromycin-resistance genes (ermA, ermB, ermC, mefA, msrA). Electron microscopy showed no major structural damage to bacteria, suggesting the synergistic mechanism operates at the molecular level rather than through physical membrane destruction.","whyItMatters":"With antibiotic resistance rising globally and few new antibiotics in development, finding ways to make existing antibiotics work again is critical. This study shows that pairing a peptide with traditional antibiotics can restore effectiveness against bacteria that have become resistant — offering a potential combination therapy strategy against superbugs.","specificNumbers":"","methodology":"Researchers used the checkerboard method to evaluate synergy between two antimicrobial peptides (DP7 and CLS001) and four antibiotics (gentamicin, vancomycin, azithromycin, and amoxicillin) against clinical isolates of S. aureus, P. aeruginosa, A. baumannii, and E. coli. Resistance genes were identified using quantitative PCR. Transmission electron microscopy was used to examine bacterial morphology after combination treatment.","limitations":"This was an in vitro (lab dish) study, so results may not directly translate to treating infections in living organisms. The number of clinical isolates tested for each species was limited. The molecular mechanism behind the DP7-azithromycin synergy was not fully elucidated. No animal infection models or toxicity data were reported."},{"rthcId":"RPEP-03527","title":"Curcumin alleviates lumbar radiculopathy by reducing neuroinflammation, oxidative stress and nociceptive factors.","authors":"Xiao, L; Ding, M; Fernandez, A; Zhao, P; Jin, L; Li, X","year":2017,"journal":"European cells & materials, 33, 279-293","doi":"10.22203/eCM.v033a21","pmid":"28485773","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03528","title":"Trypsin induces biphasic muscle contraction and relaxation via transient receptor potential vanilloid 1 and neurokinin receptors 1/2 in porcine esophageal body.","authors":"Xiaopeng, Bai; Tanaka, Yoshimasa; Ihara, Eikichi; Hirano, Katsuya; Nakano, Kayoko; Hirano, Mayumi; Oda, Yoshinao; Nakamura, Kazuhiko","year":2017,"journal":"European journal of pharmacology, 797, 65-74","doi":"10.1016/j.ejphar.2017.01.004","pmid":"28088386","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Trypsin induced a concentration-dependent biphasic response (contraction at 100 nM, relaxation at 1 μM) exclusively in esophageal circular smooth muscle, not longitudinal muscle. The response was mediated through a PAR2 → TRPV1 → substance P signaling pathway in sensory neurons, with substance P acting via neurokinin receptors NK1 and NK2.\n\nGap junctions between smooth muscle cells were essential for the response — gap junction uncouplers (carbenoxolone and octanol) abolished the trypsin-induced contractions entirely. The PAR2-activating peptide SLIGKV-NH2 produced only contraction (monophasic), suggesting the relaxation component involves additional mechanisms at higher trypsin concentrations.","whyItMatters":"Gastroesophageal reflux disease (GERD) is extremely common, and cases that don't respond to standard acid-suppressing treatment may involve duodenal reflux containing trypsin. Understanding how trypsin disrupts esophageal muscle function through neuropeptide signaling could lead to new therapeutic approaches for refractory GERD targeting the PAR2-substance P pathway rather than acid production alone.","specificNumbers":"","methodology":"Researchers performed organ bath experiments on isolated circular and longitudinal smooth muscle strips from porcine esophageal body. They applied trypsin at various concentrations and measured contractile responses, then used selective receptor antagonists and channel blockers to dissect the signaling pathway. Tetrodotoxin was used to assess neural involvement, gap junction uncouplers to test intercellular communication, and specific NK1, NK2, and NK3 antagonists to identify the relevant neurokinin receptors.","limitations":"This study used porcine esophageal tissue, which may differ from human esophageal physiology. The experiments were conducted on isolated muscle strips in an organ bath, which removes the influence of intact neural circuits and blood supply present in vivo. Additionally, the study focused on acute responses and does not address chronic effects of trypsin exposure relevant to ongoing GERD."},{"rthcId":"RPEP-03529","title":"Systemic administration of anorexic gut peptide hormones impairs hedonic-driven sucrose consumption in mice.","authors":"Yamaguchi, Erina; Yasoshima, Yasunobu; Shimura, Tsuyoshi","year":2017,"journal":"Physiology & behavior, 171, 158-164","doi":"10.1016/j.physbeh.2016.12.034","pmid":"28040488","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03530","title":"Anti‑inflammatory actions of gabapentin and pregabalin on the substance P‑induced mitogen‑activated protein kinase activation in U373 MG human glioblastoma astrocytoma cells.","authors":"Yamaguchi, Keisuke; Kumakura, Seiichiro; Someya, Akimasa; Iseki, Masako; Inada, Eiichi; Nagaoka, Isao","year":2017,"journal":"Molecular medicine reports, 16(5), 6109-6115","doi":"10.3892/mmr.2017.7368","pmid":"28849160","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03531","title":"Ketamine suppresses the substance P-induced production of IL-6 and IL-8 by human U373MG glioblastoma/astrocytoma cells.","authors":"Yamaguchi, Keisuke; Kumakura, Seiichiro; Murakami, Taisuke; Someya, Akimasa; Inada, Eiichi; Nagaoka, Isao","year":2017,"journal":"International journal of molecular medicine, 39(3), 687-692","doi":"10.3892/ijmm.2017.2875","pmid":"28204809","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03532","title":"Cardiovascular benefits of the newer medications for treating type 2 diabetes mellitus.","authors":"Yandrapalli, Srikanth; Aronow, Wilbert S","year":2017,"journal":"Journal of thoracic disease, 9(7), 2124-2134","doi":"10.21037/jtd.2017.06.70","pmid":"28840014","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review establishes that hyperglycemia alone plays a limited role in cardiovascular disease progression in T2DM — metabolic risk factors like insulin resistance, hypertension, obesity, and dyslipidemia are the major drivers. GLP-1 receptor agonists and SGLT-2 inhibitors demonstrated cardiovascular benefits in their safety trials, attributed to diverse extra-pancreatic effects beyond glucose control.\n\nThese benefits include reductions in blood pressure, body weight, and lipid abnormalities. The review proposes studying combinations of GLP-1 RAs, SGLT-2 inhibitors, and pioglitazone in high-risk diabetic patients and even in non-diabetic patients with insulin resistance for potential cardiovascular protection.","whyItMatters":"This review captures a pivotal shift in diabetes treatment philosophy — from focusing solely on blood sugar control to addressing the broader metabolic syndrome that drives cardiovascular death. Understanding that GLP-1 agonists work through multiple cardiovascular protective mechanisms beyond glucose lowering has fundamentally changed how these drugs are prescribed and has expanded their use to patients whose primary need is cardiovascular protection.","specificNumbers":"","methodology":"This is a narrative review article discussing the cardiovascular benefits observed in major cardiovascular outcome trials (CVOTs) of GLP-1 receptor agonists and SGLT-2 inhibitors. The review synthesizes evidence from clinical trials and mechanistic studies to explain the cardiovascular protective effects of these newer diabetes medications.","limitations":"Published in 2017, this review predates many subsequent cardiovascular outcome trials and guideline updates. The evidence for some GLP-1 agonists was limited at the time of writing. The review is narrative rather than systematic, introducing potential selection bias. Long-term cardiovascular outcomes (beyond trial durations) were not available. Cost-effectiveness analyses were not included despite the high cost of newer agents."},{"rthcId":"RPEP-03533","title":"Identification of the first cathelicidin gene from skin of Chinese giant salamanders Andrias davidianus with its potent antimicrobial activity.","authors":"Yang, Hui; Lu, Baoyue; Zhou, Dandan; Zhao, Lin; Song, Weijia; Wang, Lixin","year":2017,"journal":"Developmental and comparative immunology, 77, 141-149","doi":"10.1016/j.dci.2017.08.002","pmid":"28801228","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03534","title":"The fast track to canonical Wnt signaling in MC3T3-E1 cells protected by substance P against serum deprivation-induced apoptosis.","authors":"Yang, Jianguo; Nie, Jiping; Fu, Su; Liu, Song; Wu, Jianqun; Cui, Liang; Zhang, Yongtao; Yu, Bin","year":2017,"journal":"Cell biology international, 41(1), 71-78","doi":"10.1002/cbin.10676","pmid":"27592589","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03535","title":"X-ray structure of a protease-resistant mutant form of human galectin-9 having two carbohydrate recognition domains with a metal-binding site.","authors":"Yoshida, Hiromi; Nishi, Nozomu; Wada, Kenji; Nakamura, Takanori; Hirashima, Mitsuomi; Kuwabara, Naoyuki; Kato, Ryuichi; Kamitori, Shigehiro","year":2017,"journal":"Biochemical and biophysical research communications, 490(4), 1287-1293","doi":"10.1016/j.bbrc.2017.07.009","pmid":"28687490","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03536","title":"Stapled BIG3 helical peptide ERAP potentiates anti-tumour activity for breast cancer therapeutics.","authors":"Yoshimaru, Tetsuro; Aihara, Keisuke; Komatsu, Masato; Matsushita, Yosuke; Okazaki, Yasumasa; Toyokuni, Shinya; Honda, Junko; Sasa, Mitsunori; Miyoshi, Yasuo; Otaka, Akira; Katagiri, Toyomasa","year":2017,"journal":"Scientific reports, 7(1), 1821","doi":"10.1038/s41598-017-01951-6","pmid":"28500289","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03537","title":"Z-505 hydrochloride, an orally active ghrelin agonist, attenuates the progression of cancer cachexia via anabolic hormones in Colon 26 tumor-bearing mice.","authors":"Yoshimura, Makoto; Shiomi, Yoshihiro; Ohira, Yuta; Takei, Mineo; Tanaka, Takao","year":2017,"journal":"European journal of pharmacology, 811, 30-37","doi":"10.1016/j.ejphar.2017.05.036","pmid":"28529141","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03538","title":"A novel GLP-1/GIP dual agonist is more effective than liraglutide in reducing inflammation and enhancing GDNF release in the MPTP mouse model of Parkinson's disease.","authors":"Yuan, Ziyue; Li, Dongfang; Feng, Peng; Xue, Guofang; Ji, Chenhui; Li, Guanglai; Hölscher, Christian","year":2017,"journal":"European journal of pharmacology, 812, 82-90","doi":"10.1016/j.ejphar.2017.06.029","pmid":"28666800","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03539","title":"The impact of gut hormones on the neural circuit of appetite and satiety: A systematic review.","authors":"Zanchi, Davide; Depoorter, Antoinette; Egloff, Laura; Haller, Sven; Mählmann, Laura; Lang, Undine E; Drewe, Jürgen; Beglinger, Christoph; Schmidt, André; Borgwardt, Stefan","year":2017,"journal":"Neuroscience and biobehavioral reviews, 80, 457-475","doi":"10.1016/j.neubiorev.2017.06.013","pmid":"28669754","tags":[],"studyType":"systematic review","evidenceStrength":"strong","keyFinding":"This systematic review of 40 neuroimaging studies mapped how gut peptide hormones control appetite by activating specific brain regions. The hunger hormone ghrelin activates the prefrontal cortex (decision-making), amygdala (emotional eating), and insula (body awareness) while suppressing the hypothalamus. Satiety signals — GLP-1, PYY, CCK, leptin, glucose, and insulin — do the opposite, affecting the same brain regions in reverse.\n\nThis creates a clear picture: gut peptides don't just signal 'hungry' or 'full' — they reshape activity across an entire neural circuit that governs food decisions, emotional responses to food, and metabolic regulation.","whyItMatters":"Understanding exactly which brain regions gut peptides control explains why GLP-1 drugs like semaglutide change people's entire relationship with food — not just reducing hunger but altering food cravings, emotional eating, and reward-driven eating. This review provides the neuroscience foundation for why peptide-based obesity drugs work on the brain, not just the gut, and why they may also affect alcohol cravings and other compulsive behaviors that share the same neural circuits.","specificNumbers":"349 studies screened · 40 included · 27 in healthy subjects · 13 in obese subjects · key brain regions: PFC, amygdala, insula, hypothalamus · 7 gut molecules mapped","methodology":"Systematic review of functional and neurochemical brain imaging studies (fMRI, PET) published before July 2016. Researchers searched databases for studies examining how ghrelin, GLP-1, PYY, CCK, leptin, glucose, and insulin influence brain region activation during appetite and satiety regulation. 40 of 349 identified studies met inclusion criteria.","limitations":"Heterogeneous study designs and imaging methods across the 40 included studies. Most studies measured correlations rather than causation. Only 13 studies included obese subjects, limiting conclusions about how these circuits differ in obesity. Published before the GLP-1 drug explosion — newer neuroimaging studies of semaglutide and tirzepatide were not captured. Small sample sizes in most included studies."},{"rthcId":"RPEP-03540","title":"Synthesis and structure-activity studies on novel analogs of human growth hormone releasing hormone (GHRH) with enhanced inhibitory activities on tumor growth.","authors":"Zarandi, Marta; Cai, Renzhi; Kovacs, Magdolna; Popovics, Petra; Szalontay, Luca; Cui, Tengjiao; Sha, Wei; Jaszberenyi, Miklos; Varga, Jozsef; Zhang, XianYang; Block, Norman L; Rick, Ferenc G; Halmos, Gabor; Schally, Andrew V","year":2017,"journal":"Peptides, 89, 60-70","doi":"10.1016/j.peptides.2017.01.009","pmid":"28130121","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03541","title":"Relamorelin and other ghrelin receptor agonists - future options for gastroparesis, functional dyspepsia and proton pump inhibitors-resistant non-erosive reflux disease.","authors":"Zatorski, H; Mosinska, P; Storr, M; Fichna, J","year":2017,"journal":"Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 68(6), 797-805","doi":null,"pmid":"29550791","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03542","title":"Improvement of activity-related knee joint discomfort following supplementation of specific collagen peptides.","authors":"Zdzieblik, Denise; Oesser, Steffen; Gollhofer, Albert; König, Daniel","year":2017,"journal":"Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme, 42(6), 588-595","doi":"10.1139/apnm-2016-0390","pmid":"28177710","tags":["collagen-peptides","joint-health","sports-nutrition"],"studyType":"rct","evidenceStrength":"high","keyFinding":"Young athletes with functional knee pain who took 5 grams of bioactive collagen peptides daily for 12 weeks experienced significantly greater reduction in activity-related knee pain compared to placebo. The collagen group improved by 19.5 points on the VAS pain scale versus 13.9 points for placebo (p=0.046). Independent physician assessments confirmed the result (16.7 vs 12.2 points, p=0.021). Participants taking collagen peptides also significantly reduced their use of additional treatments like taping, physical therapy, or anti-inflammatory drugs.","whyItMatters":"Knee pain is one of the most common complaints among athletes, and conventional treatments often involve NSAIDs (which carry side effects) or rest (which interrupts training). This randomized controlled trial provides evidence that a simple oral collagen peptide supplement can meaningfully reduce activity-related knee pain in young, active people — offering a low-risk alternative or complement to standard treatments.","specificNumbers":"n=139 · 5g collagen peptides/day · 12 weeks · VAS improvement: 19.5 vs 13.9 (p=0.046) · Physician VAS: 16.7 vs 12.2 (p=0.021) · Reduced use of additional therapies","methodology":"Double-blind, randomized, placebo-controlled trial. 139 young athletic adults with functional knee pain were assigned to receive either 5 grams of bioactive collagen peptides or placebo daily for 12 weeks. Pain during activity and at rest was measured using a visual analogue scale (VAS) by both participants and physicians. Secondary outcomes included knee range of motion and use of additional treatments.","limitations":"The difference between groups, while statistically significant, was relatively modest (about 5.6 VAS points for self-reported, 4.5 for physician-assessed). Resting pain did not reach statistical significance. Range of motion showed no improvement, though this may reflect that participants had normal baseline mobility. The study was funded by GELITA AG, a collagen manufacturer, and one author (Oesser) is affiliated with the collagen research institute."},{"rthcId":"RPEP-03543","title":"Upregulated expression of substance P (SP) and NK1R in eczema and SP-induced mast cell accumulation.","authors":"Zhan, Mengmeng; Zheng, Wenjiao; Jiang, Qijun; Zhao, Zuotao; Wang, Zhiyun; Wang, Junling; Zhang, Huiyun; He, Shaoheng","year":2017,"journal":"Cell biology and toxicology, 33(4), 389-405","doi":"10.1007/s10565-016-9379-0","pmid":"28154998","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03544","title":"Rational design of charged peptides that self-assemble into robust nanofibers as immune-functional scaffolds.","authors":"Zhang, Hangyu; Park, Jaehyung; Jiang, Yonghou; Woodrow, Kim A","year":2017,"journal":"Acta biomaterialia, 55, 183-193","doi":"10.1016/j.actbio.2017.03.041","pmid":"28365480","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03545","title":"Diversity-Oriented Synthesis of Cyclic Azapeptides by A3 -Macrocyclization Provides High-Affinity CD36-Modulating Peptidomimetics.","authors":"Zhang, Jinqiang; Mulumba, Mukandila; Ong, Huy; Lubell, William D","year":2017,"journal":"Angewandte Chemie (International ed. in English), 56(22), 6284-6288","doi":"10.1002/anie.201611685","pmid":"28090719","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03546","title":"Chronic administration of mitochondrion-targeted peptide SS-31 prevents atherosclerotic development in ApoE knockout mice fed Western diet.","authors":"Zhang, Meng; Zhao, Hongting; Cai, Jing; Li, Huihui; Wu, Qi; Qiao, Tong; Li, Kuanyu","year":2017,"journal":"PloS one, 12(9), e0185688","doi":"10.1371/journal.pone.0185688","pmid":"28961281","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Chronic subcutaneous administration of the mitochondria-targeted peptide SS-31 at 1 mg/kg/day and 3 mg/kg/day for 12 weeks reduced atherosclerotic plaque area and size in ApoE knockout mice fed a Western diet. SS-31 suppressed oxidative stress (reduced DHE staining, lower 8-OHDG, increased SOD activity), reduced systemic inflammation (decreased ICAM-1, MCP-1, and IL-6 levels), and inhibited cholesterol influx by downregulating CD36 and LOX-1 expression, preventing foam cell formation. Plaque composition also changed, suggesting more stable plaques.","whyItMatters":"Atherosclerosis is the leading cause of heart attacks and strokes, and current treatments primarily manage cholesterol levels and symptoms rather than directly targeting the oxidative stress and mitochondrial dysfunction that drive plaque formation. SS-31 (also known as elamipretide) targets the root cause — mitochondrial dysfunction — by binding cardiolipin in the inner mitochondrial membrane. This study suggests that protecting mitochondrial function could be a novel therapeutic strategy for preventing cardiovascular disease.","specificNumbers":"2 doses tested: 1 mg/kg/d and 3 mg/kg/d · 12 weeks of treatment · Reduced plaque area · Decreased ICAM-1, MCP-1, IL-6 · Increased SOD activity · Downregulated CD36 and LOX-1","methodology":"Male ApoE knockout mice (8 weeks old) were fed a Western diet and received daily subcutaneous injections of either saline (control) or SS-31 (1 mg/kg/d or 3 mg/kg/d) for 12 weeks. Atherosclerotic plaques were assessed by Oil Red O staining. Oxidative stress was measured by DHE staining and 8-OHDG immunohistochemistry. ATP levels, SOD activity, inflammatory markers (ICAM-1, MCP-1, IL-6, CRP), cholesterol transport receptors (CD36, LOX-1, ABCA1), and plaque composition (CD68, α-SMA, Masson's trichrome) were analyzed.","limitations":"This is a mouse study using a genetic model of atherosclerosis (ApoE knockout) that does not perfectly replicate human cardiovascular disease. The ApoE knockout model develops much more aggressive atherosclerosis than typically occurs in humans. Specific quantitative results (percentage reductions in plaque area, inflammation markers) are not provided in the abstract. Long-term safety of chronic SS-31 administration was not assessed."},{"rthcId":"RPEP-03547","title":"Up-regulated expression of substance P in CD8+ T cells and NK1R on monocytes of atopic dermatitis.","authors":"Zhang, Zenan; Zheng, Wenjiao; Xie, Hua; Chai, Ruonan; Wang, Junling; Zhang, Huiyun; He, Shaoheng","year":2017,"journal":"Journal of translational medicine, 15(1), 93","doi":"10.1186/s12967-017-1196-6","pmid":"28460633","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03548","title":"Role of mitochondrial dysfunction in renal fibrosis promoted by hypochlorite-modified albumin in a remnant kidney model and protective effects of antioxidant peptide SS-31.","authors":"Zhao, Hao; Liu, Yan-Jun; Liu, Zong-Rui; Tang, Dong-Dong; Chen, Xiao-Wen; Chen, Yi-Hua; Zhou, Ru-Ning; Chen, Si-Qi; Niu, Hong-Xin","year":2017,"journal":"European journal of pharmacology, 804, 57-67","doi":"10.1016/j.ejphar.2017.03.037","pmid":"28322835","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03549","title":"Peptide SS-31 upregulates frataxin expression and improves the quality of mitochondria: implications in the treatment of Friedreich ataxia.","authors":"Zhao, Hongting; Li, Huihui; Hao, Shuangying; Chen, Jiping; Wu, Jing; Song, Chuanhui; Zhang, Meng; Qiao, Tong; Li, Kuanyu","year":2017,"journal":"Scientific reports, 7(1), 9840","doi":"10.1038/s41598-017-10320-2","pmid":"28852135","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03550","title":"GHK Peptide Inhibits Bleomycin-Induced Pulmonary Fibrosis in Mice by Suppressing TGFβ1/Smad-Mediated Epithelial-to-Mesenchymal Transition.","authors":"Zhou, Xiao-Ming; Wang, Gui-Liang; Wang, Xiao-Bo; Liu, Li; Zhang, Qin; Yin, Yan; Wang, Qiu-Yue; Kang, Jian; Hou, Gang","year":2017,"journal":"Frontiers in pharmacology, 8, 904","doi":"10.3389/fphar.2017.00904","pmid":"29311918","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03551","title":"Amylin receptor ligands reduce the pathological cascade of Alzheimer's disease.","authors":"Zhu, Haihao; Xue, Xiehua; Wang, Erming; Wallack, Max; Na, Hana; Hooker, Jacob M; Kowall, Neil; Tao, Qiushan; Stein, Thor D; Wolozin, Benjamin; Qiu, Wei Qiao","year":2017,"journal":"Neuropharmacology, 119, 170-181","doi":"10.1016/j.neuropharm.2017.03.030","pmid":"28363773","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03552","title":"Mitochondria Targeted Peptide Attenuates Mitochondrial Dysfunction, Controls Inflammation and Protects Against Spinal Cord Injury-Induced Lung Injury.","authors":"Zhu, Liu-Long; Li, Mao-Qiang; He, Fan; Zhou, Shao-Bo; Jiang, Wu","year":2017,"journal":"Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 44(1), 388-400","doi":"10.1159/000484919","pmid":"29132140","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"SS-31 treatment administered immediately after spinal cord injury and for the following two days produced multiple protective effects in the lungs:\n\n- Attenuated lung edema and tissue damage\n- Reduced apoptosis (cell death) in alveolar type II cells, which are critical for lung function\n- Decreased total macrophages, pro-inflammatory M1 macrophages, and neutrophil infiltration\n- Lowered reactive oxygen species (ROS) levels\n- Reversed mitochondrial dysfunction\n- Inhibited NLRP3 inflammasome activation, a key driver of inflammatory lung damage\n\nThese results demonstrate that targeting mitochondrial dysfunction with SS-31 can control the inflammatory cascade that leads to secondary lung injury after spinal cord trauma.","whyItMatters":"Secondary organ damage — particularly to the lungs — is a major cause of complications and death after spinal cord injury, yet there are currently no targeted treatments for this problem. By showing that a mitochondria-targeted peptide can protect the lungs from SCI-induced damage through multiple mechanisms, this study opens a potential new therapeutic avenue for one of the most devastating consequences of spinal cord trauma.","specificNumbers":"","methodology":"C57BL/6 mice underwent spinal cord injury and were divided into treatment and control groups. Treatment groups received daily intraperitoneal injections of SS-31 for three days starting immediately after injury. Sham and SCI-only groups received vehicle (DMSO and 0.9% NaCl, 1:3 ratio). Lung tissue was examined for edema, tissue damage, apoptosis of alveolar type II cells, macrophage and neutrophil infiltration, reactive oxygen species levels, mitochondrial function, and NLRP3 inflammasome activation.","limitations":"This is a mouse study, and SCI-induced lung injury in rodents may differ from the human condition in important ways. The abstract does not report specific quantitative data (e.g., exact measurements of edema reduction or percentage of apoptotic cells). The three-day treatment window is very short, and longer-term outcomes are unknown. The SS-31 dose is not specified in the abstract. Only female C57BL/6 mice were used, limiting generalizability across sexes and strains."},{"rthcId":"RPEP-03553","title":"Sleep-inducing effect of substance P-cholera toxin A subunit in mice.","authors":"Zielinski, Mark R; Gerashchenko, Dmitry","year":2017,"journal":"Neuroscience letters, 659, 44-47","doi":"10.1016/j.neulet.2017.08.066","pmid":"28866052","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03554","title":"Capromorelin oral solution (ENTYCE®) increases food consumption and body weight when administered for 4 consecutive days to healthy adult Beagle dogs in a randomized, masked, placebo controlled study.","authors":"Zollers, Bill; Rhodes, Linda; Heinen, Ernst","year":2017,"journal":"BMC veterinary research, 13(1), 10","doi":"10.1186/s12917-016-0925-z","pmid":"28056951","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Dogs receiving capromorelin at 3 mg/kg daily showed a mean food consumption increase of 60.55% (±39.87%) compared to a decrease of 11.15% (±14.23%) in placebo dogs (P < 0.001). Body weight increased by a mean of 5.96% (±1.76%) in the treated group versus 0.053% (±1.14%) in controls (P < 0.001).\n\nThe drug was well-tolerated across all 12 treated dogs, with no abnormalities on physical examination, serum chemistry, or hematology. The only observed clinical sign was increased salivation in some treated dogs. This demonstrated that activating the ghrelin receptor can dramatically and safely stimulate appetite in dogs.","whyItMatters":"Loss of appetite is a common and serious problem in sick dogs, contributing to muscle wasting, delayed recovery, and death. Capromorelin represents the first drug specifically designed to address this through a novel mechanism — mimicking the hunger hormone ghrelin. Its success in veterinary medicine has also served as proof of concept for ghrelin receptor agonists more broadly, informing human research into appetite stimulation for conditions like cancer cachexia and age-related wasting.","specificNumbers":"","methodology":"This was a randomized, masked (blinded), placebo-controlled study in healthy adult Beagle dogs. Twelve dogs (6 males, 6 females) received capromorelin oral solution at 3 mg/kg daily for 4 consecutive days, while 12 matched controls received placebo. Food consumption and body weight were measured throughout. Physical examinations, serum chemistry, and hematology were evaluated before and after treatment to assess safety.","limitations":"The study used only healthy dogs, so results may not directly apply to dogs with underlying disease that causes appetite loss. The sample size was small (12 per group) and the treatment duration was only 4 days, leaving long-term efficacy and safety unknown from this study alone. Beagles may not represent all dog breeds. The dramatic food consumption increase in healthy dogs may overestimate effects in clinically ill animals."},{"rthcId":"RPEP-03555","title":"Cyclic peptide therapeutics: past, present and future.","authors":"Zorzi, Alessandro; Deyle, Kaycie; Heinis, Christian","year":2017,"journal":"Current opinion in chemical biology, 38, 24-29","doi":"10.1016/j.cbpa.2017.02.006","pmid":"28249193","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Over 40 cyclic peptide drugs are currently in clinical use, with approximately one new cyclic peptide drug entering the market annually. While the vast majority of approved cyclic peptides derive from natural products (antimicrobials, human peptide hormones), new techniques based on rational design and in vitro evolution now enable de novo development of cyclic peptide ligands for previously untargetable proteins. Several de novo-designed cyclic peptides are already under clinical evaluation.","whyItMatters":"Cyclic peptides occupy a unique therapeutic space between small molecule drugs and large biologics, combining the best properties of both. The ability to now design them from scratch — rather than relying solely on natural products — dramatically expands their potential to address diseases where no natural peptide solution exists.","specificNumbers":"","methodology":"This is a review article surveying the landscape of cyclic peptide therapeutics, examining approved drugs, those in clinical trials, and emerging development techniques including rational design and in vitro evolution approaches.","limitations":"As a review published in 2017, it does not cover developments from the past several years, a period of rapid advancement in peptide therapeutics. The review focuses on the overview landscape rather than providing detailed clinical efficacy data for individual drugs. The projection of continued growth relies on trends that may be affected by regulatory, manufacturing, or economic factors."},{"rthcId":"RPEP-03556","title":"Macrocyclization of a potent PACE4 inhibitor: Benefits and limitations.","authors":"Łepek, Teresa; Kwiatkowska, Anna; Couture, Frédéric; Ly, Kévin; Desjardins, Roxane; Dory, Yves; Prahl, Adam; Day, Robert","year":2017,"journal":"European journal of cell biology, 96(5), 476-485","doi":"10.1016/j.ejcb.2017.04.001","pmid":"28483279","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03557","title":"Zn(II) - pramlintide: Stability, binding sites and unexpected aggregation.","authors":"Łoboda, D; Rowińska-Żyrek, M","year":2017,"journal":"Journal of inorganic biochemistry, 174, 150-155","doi":"10.1016/j.jinorgbio.2017.06.008","pmid":"28672144","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03558","title":"Frias 2018 Efficacy And Safety Of","authors":"","year":2018,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03559","title":"Kendler 2018 Vero Teriparatide Risedronate","authors":"","year":2018,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03560","title":"Saleem 2018 Prolactin Biology And Laboratory","authors":"","year":2018,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03561","title":"Seiwerth 2018 Bpc 157 And Standard","authors":"","year":2018,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03562","title":"Wang 2018 Lipidmodified Cellpenetrating Peptidebased Selfassemblylfassembly","authors":"","year":2018,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03563","title":"Clinical parameters of ovarian hyperstimulation syndrome following different hormonal triggers of oocyte maturation in IVF treatment.","authors":"Abbara, A; Islam, R; Clarke, S A; Jeffers, L; Christopoulos, G; Comninos, A N; Salim, R; Lavery, S A; Vuong, T N L; Humaidan, P; Kelsey, T W; Trew, G H; Dhillo, W S","year":2018,"journal":"Clinical endocrinology, 88(6), 920-927","doi":"10.1111/cen.13569","pmid":"29446481","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03564","title":"Bioactive Peptides Derived from Seaweed Protein and Their Health Benefits: Antihypertensive, Antioxidant, and Antidiabetic Properties.","authors":"Admassu, Habtamu; Gasmalla, Mohammed Abdalbasit A; Yang, Ruijin; Zhao, Wei","year":2018,"journal":"Journal of food science, 83(1), 6-16","doi":"10.1111/1750-3841.14011","pmid":"29227526","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Peptides isolated from seaweed proteins have demonstrated ACE-inhibiting (blood pressure-lowering), antioxidant, and antidiabetic activities in laboratory studies. Multiple seaweed species have yielded bioactive peptides through enzymatic hydrolysis that could serve as functional food ingredients or drug candidates for cardiovascular disease and diabetes prevention. However, most evidence comes from in vitro studies, and large-scale production, in vivo validation, and safety testing are still needed.","whyItMatters":"Cardiovascular disease and diabetes are the leading causes of death globally. Finding new peptide-based treatments from sustainable sources like seaweed could provide affordable, food-derived therapeutic options. Seaweed is abundant, renewable, and already part of many diets worldwide, making it an attractive platform for bioactive peptide production.","specificNumbers":"","methodology":"This is a review article summarizing recent research on the production, isolation, and health effects of bioactive peptides derived from seaweed proteins. The authors surveyed published studies on ACE inhibition, antihypertensive, antioxidant, and antidiabetic properties of these peptides.","limitations":"Most studies reviewed were conducted in laboratory settings (in vitro), with limited in vivo or human clinical data. Large-scale production methods haven't been established. Peptide stability during digestion, interactions with other drugs or foods, and long-term safety are still unknown."},{"rthcId":"RPEP-03565","title":"Ghrelin and LEAP-2: Rivals in Energy Metabolism.","authors":"Al-Massadi, Omar; Müller, Timo; Tschöp, Matthias; Diéguez, Carlos; Nogueiras, Ruben","year":2018,"journal":"Trends in pharmacological sciences, 39(8), 685-694","doi":"10.1016/j.tips.2018.06.004","pmid":"30037389","tags":["gut-and-metabolic-peptides","obesity-and-weight-management"],"studyType":"narrative-review","evidenceStrength":"low-moderate","keyFinding":"LEAP-2 (liver-expressed antimicrobial peptide 2) is a recently discovered endogenous antagonist of the ghrelin receptor (GHSR1a). It works as a noncompetitive allosteric blocker — meaning it doesn't compete with ghrelin directly but instead changes the receptor's shape to prevent ghrelin from activating it. In lab experiments, LEAP-2 blocked ghrelin's ability to trigger calcium signaling, and in animal studies, it impaired ghrelin's metabolic effects.\n\nThe review presents LEAP-2 as ghrelin's natural counterbalance in energy metabolism: where ghrelin drives hunger and promotes fat storage, LEAP-2 opposes these effects. This makes LEAP-2 a promising therapeutic target for obesity and metabolic diseases involving ghrelin system dysregulation.","whyItMatters":"For over 20 years, ghrelin was the only known hormone that stimulates appetite. The discovery of LEAP-2 as its natural antagonist fundamentally changes our understanding of hunger regulation — it's not just about ghrelin levels, but the balance between ghrelin and LEAP-2. This opens an entirely new therapeutic avenue: rather than blocking ghrelin directly, boosting LEAP-2 could suppress appetite through the body's own counterregulatory system.","specificNumbers":"LEAP-2 = endogenous GHSR1a antagonist · Noncompetitive allosteric mechanism · Blocks ghrelin-induced Ca²⁺ release in vitro · In vivo metabolic effects confirmed","methodology":"Narrative review synthesizing recent discoveries about LEAP-2's role as a ghrelin receptor antagonist, covering molecular pharmacology (in vitro receptor studies), in vivo metabolic effects, and therapeutic implications for obesity and metabolic disease.","limitations":"Narrative review without systematic methodology. LEAP-2 research was very early-stage when this was published. Most evidence was from in vitro receptor studies and animal models. Human clinical data on LEAP-2 modulation was absent. The therapeutic potential discussed was largely speculative at time of publication."},{"rthcId":"RPEP-03566","title":"Pathogenesis-related proteins and peptides as promising tools for engineering plants with multiple stress tolerance.","authors":"Ali, Sajad; Ganai, Bashir Ahmad; Kamili, Azra N; Bhat, Ajaz Ali; Mir, Zahoor Ahmad; Bhat, Javaid Akhter; Tyagi, Anshika; Islam, Sheikh Tajamul; Mushtaq, Muntazir; Yadav, Prashant; Rawat, Sandhya; Grover, Anita","year":2018,"journal":"Microbiological research, 212-213, 29-37","doi":"10.1016/j.micres.2018.04.008","pmid":"29853166","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03567","title":"Biosynthesis of 2-aminooctanoic acid and its use to terminally modify a lactoferricin B peptide derivative for improved antimicrobial activity.","authors":"Almahboub, Sarah A; Narancic, Tanja; Devocelle, Marc; Kenny, Shane T; Palmer-Brown, William; Murphy, Cormac; Nikodinovic-Runic, Jasmina; O'Connor, Kevin E","year":2018,"journal":"Applied microbiology and biotechnology, 102(2), 789-799","doi":"10.1007/s00253-017-8655-0","pmid":"29177937","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03568","title":"Bypassing major venous occlusion and duodenal lesions in rats, and therapy with the stable gastric pentadecapeptide BPC 157, L-NAME and L-arginine.","authors":"Amic, Fedor; Drmic, Domagoj; Bilic, Zdenko; Krezic, Ivan; Zizek, Helena; Peklic, Marina; Klicek, Robert; Pajtak, Alen; Amic, Enio; Vidovic, Tinka; Rakic, Mislav; Milkovic Perisa, Marija; Horvat Pavlov, Katarina; Kokot, Antonio; Tvrdeic, Ante; Boban Blagaic, Alenka; Zovak, Mario; Seiwerth, Sven; Sikiric, Predrag","year":2018,"journal":"World journal of gastroenterology, 24(47), 5366-5378","doi":"10.3748/wjg.v24.i47.5366","pmid":"30598581","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03569","title":"Tissue-dependent induction of antimicrobial peptide genes after body wall injury in house fly (Musca domestica) larvae.","authors":"Andoh, Minako; Ueno, Takayuki; Kawasaki, Kiyoshi","year":2018,"journal":"Drug discoveries & therapeutics, 12(6), 355-362","doi":"10.5582/ddt.2018.01063","pmid":"30674770","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03570","title":"Novel ultrashort self-assembling peptide bioinks for 3D culture of muscle myoblast cells.","authors":"Arab, Wafaa; Rauf, Sakandar; Al-Harbi, Ohoud; Hauser, Charlotte A E","year":2018,"journal":"International journal of bioprinting, 4(2), 129","doi":"10.18063/IJB.v4i2.129","pmid":"33102913","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03571","title":"Clarithromycin Enhances the Antibacterial Activity and Wound Healing Capacity in Type 2 Diabetes Mellitus by Increasing LL-37 Load on Neutrophil Extracellular Traps.","authors":"Arampatzioglou, Athanasios; Papazoglou, Dimitrios; Konstantinidis, Theocharis; Chrysanthopoulou, Akrivi; Mitsios, Alexandros; Angelidou, Iliana; Maroulakou, Ioanna; Ritis, Konstantinos; Skendros, Panagiotis","year":2018,"journal":"Frontiers in immunology, 9, 2064","doi":"10.3389/fimmu.2018.02064","pmid":"30250474","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Neutrophil extracellular traps (NETs) from type 2 diabetes patients contained LL-37 but lacked antibacterial activity compared to healthy controls. Key findings:\n\n- NETs from both treatment-naive hyperglycemic and well-controlled diabetic patients failed to kill E. coli effectively\n- Clarithromycin significantly increased LL-37 externalization on NETs from well-controlled diabetic patients\n- This restored NET antibacterial capacity against E. coli\n- Clarithromycin-enhanced NETs promoted wound healing by activating and differentiating primary skin fibroblasts\n- The effect required well-controlled blood sugar (normoglycemic T2D patients), not treatment-naive hyperglycemic patients","whyItMatters":"Diabetic foot ulcers and wound infections are major complications that can lead to amputations. Understanding that the antimicrobial peptide LL-37 is deficient on diabetic NETs — and that clarithromycin can restore it — opens a new therapeutic strategy. This dual benefit of infection control and wound healing promotion through a single peptide pathway could significantly improve diabetic wound management.","specificNumbers":"","methodology":"Peripheral blood neutrophils were isolated from three groups: treatment-naive hyperglycemic T2D patients, normoglycemic well-controlled T2D patients, and healthy controls. NET release and LL-37 content were studied. Co-culture systems tested NETs against E. coli for antibacterial activity and with primary skin fibroblasts for wound healing. Clarithromycin's effects were assessed. Analysis used immunofluorescence confocal microscopy, ELISA, immunoblotting, and qRT-PCR.","limitations":"This was an in vitro study — the effects of clarithromycin on LL-37 and wound healing were demonstrated in cell culture, not in living patients. The sample size of each patient group was not specified in the abstract. The wound healing assessment used fibroblast co-cultures, which is a simplified model of the complex in vivo wound environment. Clinical trials would be needed to confirm therapeutic benefit in diabetic patients."},{"rthcId":"RPEP-03572","title":"Peptides Acting as Cognitive Enhancers.","authors":"Asua, Diego; Bougamra, Ghassen; Calleja-Felipe, María; Morales, Miguel; Knafo, Shira","year":2018,"journal":"Neuroscience, 370, 81-87","doi":"10.1016/j.neuroscience.2017.10.002","pmid":"29030286","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03573","title":"Neuropeptides in asthma, chronic obstructive pulmonary disease and cystic fibrosis.","authors":"Atanasova, Kalina R; Reznikov, Leah R","year":2018,"journal":"Respiratory research, 19(1), 149","doi":"10.1186/s12931-018-0846-4","pmid":"30081920","tags":[],"studyType":"review","evidenceStrength":"moderate","keyFinding":"This review consolidates evidence on how neuropeptides — signaling molecules released by nerves in the airways — contribute to asthma, COPD, and cystic fibrosis. The nervous system doesn't just control breathing; it actively drives disease processes like excessive mucus production, airway smooth muscle contraction, and inflammation through peptides like substance P, CGRP, VIP, and others.\n\nThe authors highlight that mucus hypersecretion is a shared feature across all three diseases, and neuropeptides play a central but underappreciated role in driving it. They also identify several less-studied neuropeptides that deserve more research attention as potential therapeutic targets.","whyItMatters":"Asthma, COPD, and cystic fibrosis collectively affect hundreds of millions of people worldwide. Current treatments often focus on inflammation or infection, but this review argues that the nervous system's peptide signaling is an overlooked driver of disease symptoms — particularly the dangerous mucus buildup that blocks airways. Understanding which neuropeptides are involved could open new treatment approaches targeting the neural side of these diseases.","specificNumbers":"3 diseases reviewed (asthma, COPD, cystic fibrosis) · Focus on mucus hypersecretion as common feature · Multiple neuropeptides examined including substance P, CGRP, VIP","methodology":"This is a narrative review that synthesizes published research on neuropeptides in airway diseases. The authors examined existing literature on both well-studied and lesser-known neuropeptides, with particular emphasis on their roles in mucus secretion and airway pathology across asthma, COPD, and cystic fibrosis.","limitations":"As a review article, this paper synthesizes existing findings rather than presenting new experimental data. The depth of evidence varies considerably between the neuropeptides discussed — some have extensive research support while others are largely speculative. The review acknowledges significant knowledge gaps, particularly regarding the precise mechanisms by which neuropeptides drive mucus phenotypes in each disease."},{"rthcId":"RPEP-03574","title":"Melanocortin 4 Receptor Pathway Dysfunction in Obesity: Patient Stratification Aimed at MC4R Agonist Treatment.","authors":"Ayers, Kristin L; Glicksberg, Benjamin S; Garfield, Alastair S; Longerich, Simonne; White, Joseph A; Yang, Pengwei; Du, Lei; Chittenden, Thomas W; Gulcher, Jeffery R; Roy, Sophie; Fiedorek, Fred; Gottesdiener, Keith; Cohen, Sarah; North, Kari E; Schadt, Eric E; Li, Shuyu D; Chen, Rong; Van der Ploeg, Lex H T","year":2018,"journal":"The Journal of clinical endocrinology and metabolism, 103(7), 2601-2612","doi":"10.1210/jc.2018-00258","pmid":"29726959","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03575","title":"Cardiovascular Effects of Different GLP-1 Receptor Agonists in Patients with Type 2 Diabetes.","authors":"Bahtiyar, Gül; Pujals-Kury, Jean; Sacerdote, Alan","year":2018,"journal":"Current diabetes reports, 18(10), 92","doi":"10.1007/s11892-018-1043-z","pmid":"30171481","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03576","title":"P53, GHRH, inflammation and cancer.","authors":"Barabutis, Nektarios; Schally, Andrew V; Siejka, Agnieszka","year":2018,"journal":"EBioMedicine, 37, 557-562","doi":"10.1016/j.ebiom.2018.10.034","pmid":"30344124","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GHRH (Growth Hormone-Releasing Hormone) antagonists exert protective effects against inflammation and cancer through p53-mediated pathways. P53 — a tumor suppressor protein frequently mutated in cancers — functions not only to regulate cell cycle, senescence, and apoptosis, but also to suppress inflammation across multiple human tissues. GHRH antagonistic analogs have been developed with clinical applications spanning benign prostatic hyperplasia, breast, prostate and lung cancers, diabetes, and neurodegenerative diseases, with their beneficial effects mediated at least partly through p53 activation.","whyItMatters":"This review connects two major areas of biomedical research — GHRH peptide biology and p53 tumor suppressor pathways — in the context of inflammation and cancer. Since chronic inflammation is a well-established driver of cancer development, understanding how GHRH peptide antagonists activate p53-mediated anti-inflammatory and anticancer effects could lead to new therapeutic strategies that target both inflammation and tumor growth simultaneously.","specificNumbers":"Clinical applications: BPH, breast/prostate/lung cancers, diabetes, neurodegeneration · P53 mutated in majority of cancers · GHRH acts via specific receptors · Both antagonistic and agonistic analogs developed","methodology":"Narrative review examining the intersection of p53 biology, GHRH peptide signaling, inflammation, and cancer. The manuscript synthesizes published research on p53's anti-inflammatory role and the mechanisms by which GHRH antagonists exert protective effects through p53-dependent pathways.","limitations":"As a narrative review, no new experimental data is presented. The abstract discusses broad principles without quantifying the clinical efficacy of specific GHRH antagonists. The complex interplay between p53, GHRH, inflammation, and cancer involves many variables that make therapeutic predictions challenging."},{"rthcId":"RPEP-03577","title":"Substance P receptor in the rat indusium griseum during postnatal development.","authors":"Barbaresi, Paolo","year":2018,"journal":"Neuroscience research, 130, 23-38","doi":"10.1016/j.neures.2017.08.007","pmid":"28842244","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03578","title":"Peptidome profiles and bioactivity elucidation of buffalo-milk dairy products after gastrointestinal digestion.","authors":"Basilicata, Manuela Giovanna; Pepe, Giacomo; Sommella, Eduardo; Ostacolo, Carmine; Manfra, Michele; Sosto, Gennaro; Pagano, Giuseppe; Novellino, Ettore; Campiglia, Pietro","year":2018,"journal":"Food research international (Ottawa, Ont.), 105, 1003-1010","doi":"10.1016/j.foodres.2017.12.038","pmid":"29433190","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03579","title":"Fungicidal Potency and Mechanisms of θ-Defensins against Multidrug-Resistant Candida Species.","authors":"Basso, Virginia; Garcia, Angie; Tran, Dat Q; Schaal, Justin B; Tran, Patti; Ngole, Diana; Aqeel, Younus; Tongaonkar, Prasad; Ouellette, André J; Selsted, Michael E","year":2018,"journal":"Antimicrobial agents and chemotherapy, 62(6)","doi":"10.1128/AAC.00111-18","pmid":"29610196","tags":["defensins","antimicrobial-peptides","antifungal","drug-resistance"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"RTD-1 (rhesus theta-defensin 1) was rapidly and potently fungicidal against both drug-sensitive and multidrug-resistant C. albicans strains. It killed fungi by permeabilizing cell membranes, triggering ATP release and intracellular reactive oxygen species (ROS) accumulation. Compared to histatin 5 (a well-characterized human antifungal peptide), RTD-1 killed C. albicans at more than 200-fold lower concentrations and much more rapidly.\n\nCritically, RTD-1 was completely resistant to Candida proteases for 2 hours under conditions that rapidly and completely destroyed histatin 5 — a major advantage for therapeutic development. Testing of 14 natural theta-defensin isoforms revealed that some were more active than amphotericin B and/or caspofungin against fluconazole-resistant organisms, including the multidrug-resistant Candida auris — a pathogen the CDC considers an urgent threat.","whyItMatters":"Candida auris and other multidrug-resistant fungi are classified as urgent threats by the CDC, and the current antifungal drug arsenal is extremely limited — only three major drug classes exist. Finding new antifungal agents is arguably even more urgent than finding new antibiotics. Theta-defensins are remarkable because their circular (macrocyclic) structure makes them inherently resistant to enzyme degradation — one of the biggest barriers to peptide drug development. Their activity against C. auris at concentrations outperforming standard-of-care drugs makes them compelling templates for new antifungal therapeutics.","specificNumbers":">200-fold lower concentration than Hst 5; 14 isoforms tested; 2h complete protease resistance; active against MDR C. albicans and C. auris; some outperformed amphotericin B and caspofungin","methodology":"Researchers tested the antifungal activity of RTD-1 and 13 other natural theta-defensin isoforms against drug-sensitive and multidrug-resistant clinical isolates of Candida albicans and non-albicans species using MIC/MFC assays. They characterized the killing mechanism through cell permeabilization, ATP release, and ROS accumulation assays. They compared RTD-1's potency and speed of killing to histatin 5, assessed protease resistance against Candida enzymes, and benchmarked activity against amphotericin B and caspofungin.","limitations":"This was an in vitro (lab dish) study — no animal infection models or human data were included. While the peptides outperformed existing drugs in killing assays, real-world antifungal therapy involves pharmacokinetics, tissue distribution, toxicity, and host immune interactions that weren't assessed. The comparison with histatin 5 is informative but somewhat unfair — Hst 5 evolved for saliva, not systemic use. Manufacturing costs for macrocyclic peptides can be high. Whether fungal pathogens could develop resistance to theta-defensins over time is unknown."},{"rthcId":"RPEP-03580","title":"A Novel Peptide-Based Antimicrobial Wound Treatment is Effective Against Biofilms of Multi-Drug Resistant Wound Pathogens.","authors":"Bayramov, Danir; Li, Zhenghao; Patel, Esha; Izadjoo, Mina; Kim, Hosan; Neff, Jennifer","year":2018,"journal":"Military medicine, 183(suppl_1), 481-486","doi":"10.1093/milmed/usx135","pmid":"29635548","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03581","title":"An endogeous defensive concept, renewed cytoprotection/adaptive cytoprotection: intra(per)-oral/intragastric strong alcohol in rat. Involvement of pentadecapeptide BPC 157 and nitric oxide system.","authors":"Becejac, T; Cesarec, V; Drmic, D; Hirsl, D; Madzarac, G; Djakovic, Z; Bunjevac, I; A Zenko Sever, A; Sepac, A; Batelja Vuletic, L; Stancic Rokotov, D; Seiwerth, S; Sikiric, P","year":2018,"journal":"Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 69(3)","doi":"10.26402/jpp.2018.3.11","pmid":"30279308","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03582","title":"Polyplex System Versus Nucleofection for Human Skin Cell Transfection and Effect of Internal Ribosome Entry Site Sequence.","authors":"Becerra Colorado, Natalia Yiset; Arenas Gómez, Claudia Marcela; Patiño Vargas, Maria Isabel; Delgado Charris, Jean Paul; Muskus López, Carlos Enrique; Restrepo Múnera, Luz Marina","year":2018,"journal":"Tissue engineering. Part C, Methods, 24(4), 233-241","doi":"10.1089/ten.TEC.2017.0435","pmid":"29490605","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03583","title":"Investigating PKA-RII specificity using analogs of the PKA:AKAP peptide inhibitor STAD-2.","authors":"Bendzunas, N George; Dörfler, Sabrina; Autenrieth, Karolin; Bertinetti, Daniela; Machal, Erik M F; Kennedy, Eileen J; Herberg, Friedrich W","year":2018,"journal":"Bioorganic & medicinal chemistry, 26(6), 1174-1178","doi":"10.1016/j.bmc.2018.02.001","pmid":"29449124","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03584","title":"Vasoactive Intestinal Peptide Ameliorates Acute Myocarditis and Atherosclerosis by Regulating Inflammatory and Autoimmune Responses.","authors":"Benitez, Raquel; Delgado-Maroto, Virginia; Caro, Marta; Forte-Lago, Irene; Duran-Prado, Mario; O'Valle, Francisco; Lichtman, Andrew H; Gonzalez-Rey, Elena; Delgado, Mario","year":2018,"journal":"Journal of immunology (Baltimore, Md. : 1950), 200(11), 3697-3710","doi":"10.4049/jimmunol.1800122","pmid":"29669783","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03585","title":"Usefulness of midregional pro-adrenomedullin as a marker of organ damage and predictor of mortality in patients with sepsis.","authors":"Bernal-Morell, Enrique; García-Villalba, Eva; Vera, Maria Del Carmen; Medina, Blanca; Martinez, Monica; Callejo, Victoria; Valero, Salvador; Cinesi, Cesar; Piñera, Pascual; Alcaraz, Antonia; Marin, Irene; Muñoz, Angeles; Cano, Alfredo","year":2018,"journal":"The Journal of infection, 76(3), 249-257","doi":"10.1016/j.jinf.2017.12.003","pmid":"29246637","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03586","title":"Cardiovascular outcomes with glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes: a meta-analysis.","authors":"Bethel, M Angelyn; Patel, Rishi A; Merrill, Peter; Lokhnygina, Yuliya; Buse, John B; Mentz, Robert J; Pagidipati, Neha J; Chan, Juliana C; Gustavson, Stephanie M; Iqbal, Nayyar; Maggioni, Aldo P; Öhman, Peter; Poulter, Neil R; Ramachandran, Ambady; Zinman, Bernard; Hernandez, Adrian F; Holman, Rury R","year":2018,"journal":"The lancet. Diabetes & endocrinology, 6(2), 105-113","doi":"10.1016/S2213-8587(17)30412-6","pmid":"29221659","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across four cardiovascular outcome trials (ELIXA, LEADER, SUSTAIN 6, and EXSCEL), GLP-1 receptor agonists produced a significant 10% relative risk reduction in the composite of cardiovascular death, non-fatal heart attack, and non-fatal stroke (HR 0.90, 95% CI 0.82–0.99, p=0.033).\n\nCardiovascular mortality was reduced by 13% (HR 0.87, 95% CI 0.79–0.96, p=0.007) and all-cause mortality by 12% (HR 0.88, 95% CI 0.81–0.95, p=0.002). No significant effects were found for individual endpoints of heart attack, stroke, unstable angina hospitalization, or heart failure hospitalization when analyzed separately.","whyItMatters":"This meta-analysis provided some of the first pooled evidence that GLP-1 receptor agonists as a drug class offer cardiovascular protection — not just blood sugar control — for people with type 2 diabetes, a population at high cardiovascular risk. It helped shift clinical thinking about these drugs from glucose-lowering agents to cardioprotective therapies.","specificNumbers":"","methodology":"This was a systematic review and meta-analysis. Researchers searched PubMed and MEDLINE for randomized controlled trials comparing GLP-1 receptor agonists to placebo in adults with type 2 diabetes, with cardiovascular outcomes as primary endpoints. Four eligible trials were identified. Data were pooled using a random-effects model to calculate overall hazard ratios for cardiovascular outcomes and odds ratios for safety outcomes.","limitations":"The meta-analysis included only four trials available at the time, each testing a different GLP-1 receptor agonist with varying trial designs and patient populations. The individual drugs showed varying degrees of benefit, and the analysis could not determine whether cardiovascular protection is a true class effect or driven by specific agents. Between-trial heterogeneity, while low-to-moderate, was present."},{"rthcId":"RPEP-03587","title":"Interaction of Body Mass Index on the Association Between N-Terminal-Pro-b-Type Natriuretic Peptide and Morbidity and Mortality in Patients With Acute Heart Failure: Findings From ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure).","authors":"Bhatt, Ankeet S; Cooper, Lauren B; Ambrosy, Andrew P; Clare, Robert M; Coles, Adrian; Joyce, Emer; Krishnamoorthy, Arun; Butler, Javed; Felker, G Michael; Ezekowitz, Justin A; Armstrong, Paul W; Hernandez, Adrian F; O'Connor, Christopher M; Mentz, Robert J","year":2018,"journal":"Journal of the American Heart Association, 7(3)","doi":"10.1161/JAHA.117.006740","pmid":"29431103","tags":[],"studyType":"clinical-substudy","evidenceStrength":"moderate-high","keyFinding":"Although obese patients with acute heart failure had lower NT-proBNP levels than non-obese patients (inverse correlation, p<0.001 across BMI classes), the peptide biomarker's ability to predict death at 180 days was not affected by obesity. NT-proBNP remained a reliable prognostic indicator for long-term mortality regardless of BMI class, with no significant interaction between BMI and NT-proBNP for 180-day mortality (interaction p=0.24).\n\nHowever, for the combined endpoint of 30-day death or heart failure rehospitalization, there was a significant BMI-NT-proBNP interaction (p=0.02), suggesting the relationship between NT-proBNP and short-term outcomes may differ by weight category.","whyItMatters":"Doctors have worried that NT-proBNP blood tests are less useful in obese heart failure patients because obesity lowers natriuretic peptide levels, potentially masking disease severity. This study provides reassurance: even though obese patients have lower baseline levels, NT-proBNP still accurately predicts who is most likely to die within six months. This is clinically crucial because obesity and heart failure frequently coexist.","specificNumbers":"n=686 · Median age 67 years · 71% female · NT-proBNP inversely correlated with BMI (p<0.001) · No BMI×NT-proBNP interaction for 180-day mortality (p=0.24) · Significant interaction for 30-day death/rehospitalization (p=0.02) · 4 BMI classes analyzed","methodology":"This was a secondary analysis of 686 patients from the biomarker substudy of ASCEND-HF, a randomized clinical trial of nesiritide in acute decompensated heart failure. Patients were classified into four WHO obesity categories (non-obese, Class I, II, and III). Researchers measured NT-proBNP at baseline and assessed the interaction between BMI class and NT-proBNP levels for predicting 30-day and 180-day outcomes including death and heart failure rehospitalization.","limitations":"This is a substudy of a larger trial, so the 686-patient sample was not specifically powered for this analysis. The predominance of female participants (71%) may limit generalizability. The study examined only baseline NT-proBNP, not serial measurements. The significant interaction found for the 30-day composite endpoint but not 180-day mortality suggests the relationship may be more complex than a simple yes/no answer."},{"rthcId":"RPEP-03588","title":"Natriuretic Peptides and Normal Body Fluid Regulation.","authors":"Bie, Peter","year":2018,"journal":"Comprehensive Physiology, 8(3), 1211-1249","doi":"10.1002/cphy.c180002","pmid":"29978892","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03589","title":"Endogenous Opiates and Behavior: 2016.","authors":"Bodnar, Richard J","year":2018,"journal":"Peptides, 101, 167-212","doi":"10.1016/j.peptides.2018.01.011","pmid":"29366859","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03590","title":"Hibiscus and lemon verbena polyphenols modulate appetite-related biomarkers in overweight subjects: a randomized controlled trial.","authors":"Boix-Castejón, Marina; Herranz-López, María; Pérez Gago, Alberto; Olivares-Vicente, Mariló; Caturla, Nuria; Roche, Enrique; Micol, Vicente","year":2018,"journal":"Food & function, 9(6), 3173-3184","doi":"10.1039/c8fo00367j","pmid":"29862395","tags":[],"studyType":"randomized controlled trial","evidenceStrength":"moderate","keyFinding":"In a 60-day double-blind, placebo-controlled trial of 54 overweight subjects, a polyphenol supplement combining hibiscus and lemon verbena extracts increased the appetite-suppressing hormone GLP-1 (glucagon-like peptide-1) and decreased the hunger-promoting hormone ghrelin. Participants also showed improvements in body measurements, reduced blood pressure and heart rate, and reported a more positive overall health perception. The authors propose that these effects may be mediated through AMPK (AMP-activated protein kinase) activation, which influences energy metabolism and fat management.","whyItMatters":"GLP-1 is the same hormone targeted by blockbuster weight-loss drugs like semaglutide and tirzepatide. The finding that plant polyphenols can naturally increase GLP-1 levels is significant because it suggests a dietary approach to modulating the same appetite pathway that these drugs exploit pharmacologically. If plant-derived polyphenols can meaningfully boost endogenous GLP-1 production, this could complement or provide a more accessible alternative to expensive injectable medications for appetite management.","specificNumbers":"n=54 · 60 days · Double-blind, placebo-controlled · GLP-1 increased · Ghrelin decreased · Blood pressure and heart rate decreased","methodology":"Fifty-four overweight subjects were randomized to receive either a polyphenol supplement (combining Lippia citriodora/lemon verbena and Hibiscus sabdariffa extracts) or placebo for 60 days. Anthropometric measurements (body weight, skinfold thickness, circumferences) and blood pressure were recorded at baseline, 30, and 60 days. Hunger and satiety were tracked using a validated Visual Analogue Scale at five timepoints. Health status was assessed via the SF-36 questionnaire. Fasting blood samples were analyzed for appetite-related hormones including GLP-1 and ghrelin.","limitations":"The sample size of 54 is modest for a weight management trial. The 60-day duration is relatively short and doesn't address long-term weight maintenance. Specific effect sizes and statistical significance values for individual outcomes are not provided in the abstract. The postulated AMPK mechanism is speculative and not directly measured in this study. The authors acknowledge further research is needed. Industry involvement is possible given the use of a proprietary supplement formulation."},{"rthcId":"RPEP-03591","title":"ACTIVExtend: 24 Months of Alendronate After 18 Months of Abaloparatide or Placebo for Postmenopausal Osteoporosis.","authors":"Bone, Henry G; Cosman, Felicia; Miller, Paul D; Williams, Gregory C; Hattersley, Gary; Hu, Ming-Yi; Fitzpatrick, Lorraine A; Mitlak, Bruce; Papapoulos, Socrates; Rizzoli, René; Dore, Robin K; Bilezikian, John P; Saag, Kenneth G","year":2018,"journal":"The Journal of clinical endocrinology and metabolism, 103(8), 2949-2957","doi":"10.1210/jc.2018-00163","pmid":"29800372","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03592","title":"Safety and efficacy of Cerebrolysin in early post-stroke recovery: a meta-analysis of nine randomized clinical trials.","authors":"Bornstein, Natan M; Guekht, Alla; Vester, Johannes; Heiss, Wolf-Dieter; Gusev, Eugene; Hömberg, Volker; Rahlfs, Volker W; Bajenaru, Ovidiu; Popescu, Bogdan O; Muresanu, Dafin","year":2018,"journal":"Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 39(4), 629-640","doi":"10.1007/s10072-017-3214-0","pmid":"29248999","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03593","title":"Benzo(a)pyrene suppresses tracheal antimicrobial peptide gene expression in bovine tracheal epithelial cells.","authors":"Bourque, Laura A; Raverty, Stephen; Co, Carmon; Lillie, Brandon N; Daoust, Pierre-Yves; Clark, Mary Ellen; Caswell, Jeff L","year":2018,"journal":"Veterinary immunology and immunopathology, 203, 40-46","doi":"10.1016/j.vetimm.2018.08.001","pmid":"30243371","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03594","title":"Amylin - Its role in the homeostatic and hedonic control of eating and recent developments of amylin analogs to treat obesity.","authors":"Boyle, Christina Neuner; Lutz, Thomas Alexander; Le Foll, Christelle","year":2018,"journal":"Molecular metabolism, 8, 203-210","doi":"10.1016/j.molmet.2017.11.009","pmid":"29203236","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03595","title":"Cerebrolysin: a multi-target drug for recovery after stroke.","authors":"Brainin, Michael","year":2018,"journal":"Expert review of neurotherapeutics, 18(8), 681-687","doi":"10.1080/14737175.2018.1500459","pmid":"30004268","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03596","title":"Normative distribution of substance P and its tachykinin neurokinin-1 receptor in the medullary serotonergic network of the human infant during postnatal development.","authors":"Bright, Fiona M; Byard, Roger W; Vink, Robert; Paterson, David S","year":2018,"journal":"Brain research bulletin, 137, 319-328","doi":"10.1016/j.brainresbull.2018.01.009","pmid":"29331576","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03597","title":"The potential role of substance P in brainstem homeostatic control in the pathogenesis of sudden infant death syndrome (SIDS).","authors":"Bright, Fiona M; Vink, Robert; Byard, Roger W","year":2018,"journal":"Neuropeptides, 70, 1-8","doi":"10.1016/j.npep.2018.02.006","pmid":"29908886","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03598","title":"Immunogenicity of a Tripartite Cell Penetrating Peptide Containing a MUC1 Variable Number of Tandem Repeat (VNTR) and A T Helper Epitope.","authors":"Brooks, Nicole; Hsu, Jennifer; Esparon, Sandra; Pouniotis, Dodie; Pietersz, Geoffrey A","year":2018,"journal":"Molecules (Basel, Switzerland), 23(9)","doi":"10.3390/molecules23092233","pmid":"30200528","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The tripartite peptide vaccine (AntpMAPMUC1tet) combined with CpG adjuvant produced enhanced antigen-specific immune responses in mice compared to the vaccine alone. Specifically, it increased interferon-gamma (IFN-γ) and IL-4 T cell responses and induced a Th1-biased immune profile characterized by a higher ratio of IgG2a to IgG1 antibodies.\n\nImportantly, vaccination generated long-term MUC1-specific antibody and T cell responses, and mice vaccinated with this construct showed delayed growth of MUC1-positive tumors. The cell-penetrating peptide component successfully delivered the branched multiple antigen peptides to antigen-presenting cells.","whyItMatters":"MUC1 is overexpressed on many cancers including breast, ovarian, and pancreatic cancers, making it an attractive vaccine target. However, peptide vaccines often struggle with poor cellular uptake and weak immune responses. This study demonstrates that cell-penetrating peptides can overcome the delivery challenge, and that combining multiple functional elements into a single peptide construct can generate the comprehensive immune response needed — both killer T cells and antibodies — for effective anti-tumor immunity.","specificNumbers":"","methodology":"Researchers synthesized a tripartite peptide construct (AntpMAPMUC1tet) containing: Antennapedia cell-penetrating peptide, branched MUC1 variable number of tandem repeat sequences with multiple T cell epitopes, and a tetanus toxoid universal T helper epitope. Mice were vaccinated with the construct alone or combined with CpG oligodeoxynucleotide adjuvant. Immune responses were measured by assessing IFN-γ and IL-4 T cell responses, antibody production and isotype ratios, and long-term immunological memory. Anti-tumor efficacy was evaluated by challenging vaccinated mice with MUC1-expressing tumors.","limitations":"This is a preclinical mouse study, and immune responses in mice may not directly predict human outcomes. The specific tumor growth delay was not quantified with statistical detail in the abstract. The study used transgenic HLA-A2 mice, which better model human immune responses but still don't fully recapitulate human cancer immunology. CpG adjuvant was necessary for optimal responses, and the vaccine alone showed weaker effects."},{"rthcId":"RPEP-03599","title":"An in silico model of cytotoxic T-lymphocyte activation in the lymph node following short peptide vaccination.","authors":"Brown, Liam V; Gaffney, Eamonn A; Wagg, Jonathan; Coles, Mark C","year":2018,"journal":"Journal of the Royal Society, Interface, 15(140)","doi":"10.1098/rsif.2018.0041","pmid":"29540543","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03600","title":"Excessive release of endogenous neuropeptide Y into cerebrospinal fluid after treatment of spontaneous subarachnoid haemorrhage and its possible impact on self-reported neuropsychological performance - results of a prospective clinical pilot study on good-grade patients.","authors":"Bründl, Elisabeth; Proescholdt, Martin; Schödel, Petra; Bele, Sylvia; Höhne, Julius; Zeman, Florian; Stoerr, Eva-Maria; Brawanski, Alexander; Schebesch, Karl-Michael","year":2018,"journal":"Neurological research, 40(12), 1001-1013","doi":"10.1080/01616412.2018.1508547","pmid":"30213237","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03601","title":"Transcellular stomach absorption of a derivatized glucagon-like peptide-1 receptor agonist.","authors":"Buckley, Stephen T; Bækdal, Tine A; Vegge, Andreas; Maarbjerg, Stine J; Pyke, Charles; Ahnfelt-Rønne, Jonas; Madsen, Kim G; Schéele, Susanne G; Alanentalo, Tomas; Kirk, Rikke K; Pedersen, Betty L; Skyggebjerg, Rikke B; Benie, Andrew J; Strauss, Holger M; Wahlund, Per-Olof; Bjerregaard, Simon; Farkas, Erzsébet; Fekete, Csaba; Søndergaard, Flemming L; Borregaard, Jeanett; Hartoft-Nielsen, Marie-Louise; Knudsen, Lotte Bjerre","year":2018,"journal":"Science translational medicine, 10(467)","doi":"10.1126/scitranslmed.aar7047","pmid":"30429357","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03602","title":"PEGylated prodrugs of antidiabetic peptides amylin and GLP-1.","authors":"Böttger, Roland; Knappe, Daniel; Hoffmann, Ralf","year":2018,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 292, 58-66","doi":"10.1016/j.jconrel.2018.05.001","pmid":"29729352","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The PEG-prodrug system used protease-cleavable peptide linkers (LVPR, LDPR, and LVPRLVPR) to release therapeutic peptides at controlled rates. Taspoglutide release could be tuned over more than one order of magnitude, providing stable serum levels from approximately 0.08 to 3 μmol/L for about 20 hours.\n\nAmylin and pramlintide levels were maintained at approximately 20 nmol/L and remained stable for at least 24 hours. Critically, the PEG attachment protected the peptides from degradation: after 24 hours in serum, less than 2% of taspoglutide within the prodrug was degraded. The researchers suggest that combining this technology with other formulation strategies could enable once-monthly administration.","whyItMatters":"Current GLP-1 and amylin-based drugs require daily or weekly injections, which can reduce patient adherence. A prodrug technology that protects these peptides from degradation while providing controlled release could dramatically extend dosing intervals. Less frequent injections would improve quality of life for millions of diabetes and obesity patients.","specificNumbers":"","methodology":"Researchers designed PEG-peptide prodrugs using three different protease-cleavable linker sequences to connect PEG to the therapeutic peptides taspoglutide (GLP-1 analog), amylin, and pramlintide (amylin analog). They measured release kinetics and stability in mouse serum, tracking both the rate of active peptide release and the degree of peptide degradation over time.","limitations":"The study was conducted in mouse serum in vitro, not in living animals or humans. In vivo pharmacokinetics, efficacy, and safety have not been tested. PEG conjugation can sometimes trigger immune responses (anti-PEG antibodies) with repeated dosing, which was not addressed. The actual achievability of once-monthly dosing is speculative and would require extensive further development and formulation optimization."},{"rthcId":"RPEP-03603","title":"Protective effects of mitochondrion-targeted peptide SS-31 against hind limb ischemia-reperfusion injury.","authors":"Cai, Jing; Jiang, Yu; Zhang, Meng; Zhao, Hongting; Li, Huihui; Li, Kuanyu; Zhang, Xin; Qiao, Tong","year":2018,"journal":"Journal of physiology and biochemistry, 74(2), 335-343","doi":"10.1007/s13105-018-0617-1","pmid":"29589186","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"SS-31 treatment conferred comprehensive protection against hind limb ischemia-reperfusion injury through multiple mechanisms:\n\n- Reduced oxidative stress: lowered malondialdehyde levels and increased SOD and catalase activities and protein levels\n- Protected mitochondria: preserved cellular ATP content and mitochondrial membrane potential, reduced cytosolic cytochrome c release\n- Suppressed inflammation: prevented IR-induced increases in TNF-α and IL-1β\n- Blocked apoptosis: maintained cleaved caspase-3 at very low levels\n- Preserved tissue integrity: prevented histological deterioration seen in vehicle controls\n\nBoth pre-ischemia and post-ischemia SS-31 administration were effective, with pre-treatment showing mildly superior protection.","whyItMatters":"Limb ischemia-reperfusion injury is a major clinical problem in vascular surgery, organ transplantation, and trauma. Current treatment options are limited. SS-31 (also known as elamipretide) is one of the most advanced mitochondria-targeted peptides in clinical development, and this study adds limb protection to its growing list of potential applications. The finding that it works both preventively and therapeutically is particularly relevant for surgical settings.","specificNumbers":"","methodology":"C57BL/6 male mice underwent hind limb ischemia-reperfusion injury. SS-31 was administered either before ischemia (preventive) or after reperfusion (therapeutic). Outcomes included histopathological assessment, oxidative stress markers (malondialdehyde, SOD, catalase), mitochondrial function (ATP content, membrane potential, cytochrome c release), inflammatory cytokines (TNF-α, IL-1β), and apoptosis markers (cleaved caspase-3). Results were compared against vehicle-treated controls.","limitations":"This was a mouse study, and ischemia-reperfusion dynamics in human limbs may differ significantly. Specific dosing details were not provided in the abstract. The study did not assess long-term functional recovery or potential adverse effects. The comparison between pre- and post-treatment was qualitative ('mildly more effective') without formal statistical comparison between timing groups."},{"rthcId":"RPEP-03604","title":"Ghrelin potentiates cardiac reactivity to stress by modulating sympathetic control and beta-adrenergic response.","authors":"Camargo-Silva, Gabriel; Turones, Larissa Córdova; da Cruz, Kellen Rosa; Gomes, Karina Pereira; Mendonça, Michelle Mendanha; Nunes, Allancer; de Jesus, Itamar Guedes; Colugnati, Diego Basile; Pansani, Aline Priscila; Pobbe, Roger Luis Henschel; Santos, Robson; Fontes, Marco Antônio Peliky; Guatimosim, Silvia; de Castro, Carlos Henrique; Ianzer, Danielle; Ferreira, Reginaldo Nassar; Xavier, Carlos Henrique","year":2018,"journal":"Life sciences, 196, 84-92","doi":"10.1016/j.lfs.2018.01.019","pmid":"29366747","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03605","title":"Combination Therapies for Obesity.","authors":"Camilleri, Michael; Acosta, Andres","year":2018,"journal":"Metabolic syndrome and related disorders, 16(8), 390-394","doi":"10.1089/met.2018.0075","pmid":"29993319","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03606","title":"Immune landscape and in vivo immunogenicity of NY-ESO-1 tumor antigen in advanced neuroblastoma patients.","authors":"Camisaschi, Chiara; Renne, Salvatore Lorenzo; Beretta, Valeria; Rini, Francesca; Spagnuolo, Rosalin Dolores; Tuccitto, Alessandra; Podda, Marta Giorgia; Parmiani, Giorgio; Rivoltini, Licia; Collini, Paola; Castelli, Chiara; Luksch, Roberto","year":2018,"journal":"BMC cancer, 18(1), 983","doi":"10.1186/s12885-018-4910-8","pmid":"30326856","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03607","title":"Oral ghrelin receptor agonist MK-0677 increases serum insulin-like growth factor 1 in hemodialysis patients: a randomized blinded study.","authors":"Campbell, Garland A; Patrie, James T; Gaylinn, Bruce D; Thorner, Michael O; Bolton, Warren K","year":2018,"journal":"Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 33(3), 523-530","doi":"10.1093/ndt/gfw474","pmid":"28340044","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"MK-0677 produced a 1.76-fold increase in geometric mean IGF-1 levels (95% CI 1.48–2.10; p < 0.001) in hemodialysis patients, compared to only a 1.07-fold change with placebo (95% CI 0.89–1.27; p = 0.718). After adjusting for baseline IGF-1, MK-0677 produced a 65% greater increase in IGF-1 compared to placebo (ratio of geometric means 1.65; 95% CI 1.33–2.04; p < 0.001).\n\nNo serious adverse effects were attributed to MK-0677 during the 3-month study period. This is the first study of MK-0677 in dialysis patients and demonstrates that the drug's ability to increase IGF-1 — previously shown in healthy subjects — is preserved in this critically ill population.","whyItMatters":"Protein-energy wasting affects a large proportion of dialysis patients and is strongly linked to increased morbidity and mortality. Current treatment options are limited — growth hormone injections require subcutaneous administration and produce unnatural GH secretion patterns. MK-0677 offers the advantage of oral dosing while maintaining normal GH secretion physiology, making it a more practical potential treatment. This study establishes safety and IGF-1 efficacy in the target population, a necessary step before larger clinical trials.","specificNumbers":"","methodology":"This was a randomized, crossover, double-blind, placebo-controlled study. Twenty-six hemodialysis patients enrolled and 22 completed the 3-month crossover design, receiving both MK-0677 and placebo in alternating periods. The primary outcome was change in serum IGF-1 levels. Statistical analysis used geometric means with 95% confidence intervals, adjusted for pre-intervention IGF-1 concentrations.","limitations":"The study had a small sample size (22 completers from 26 enrolled). While IGF-1 increased significantly, the study did not measure clinical outcomes like lean body mass, muscle strength, nutritional status, or survival — only a surrogate biomarker. The 3-month duration may be too short to detect long-term safety concerns or clinical benefits. The study was designed as a preliminary safety/efficacy assessment, not a definitive clinical trial."},{"rthcId":"RPEP-03608","title":"Morning and afternoon appetite and gut hormone responses to meal and stress challenges in obese individuals with and without binge eating disorder.","authors":"Carnell, S; Grillot, C; Ungredda, T; Ellis, S; Mehta, N; Holst, J; Geliebter, A","year":2018,"journal":"International journal of obesity (2005), 42(4), 841-849","doi":"10.1038/ijo.2017.307","pmid":"29235554","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03609","title":"The ghrelin paradox in the control of equine chondrocyte function: The good and the bad.","authors":"Ceriotti, Serena; Consiglio, Anna Lange; Casati, Lavinia; Cremonesi, Fausto; Sibilia, Valeria; Ferrucci, Francesco","year":2018,"journal":"Peptides, 103, 1-9","doi":"10.1016/j.peptides.2018.03.003","pmid":"29526750","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03610","title":"Recombinant production of bovine Lactoferrin-derived antimicrobial peptide in tobacco hairy roots expression system.","authors":"Chahardoli, Mahmood; Fazeli, Arash; Ghabooli, Mehdi","year":2018,"journal":"Plant physiology and biochemistry : PPB, 123, 414-421","doi":"10.1016/j.plaphy.2017.12.037","pmid":"29310078","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03611","title":"Cationic cell penetrating peptide modified SNARE protein VAMP8 as free chains for gene delivery.","authors":"Chen, Baizhu; Wu, Chi","year":2018,"journal":"Biomaterials science, 6(10), 2647-2655","doi":"10.1039/c8bm00672e","pmid":"30137108","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03612","title":"Commensal Bacteria-Dependent CD8αβ+ T Cells in the Intestinal Epithelium Produce Antimicrobial Peptides.","authors":"Chen, Banru; Ni, Xiang; Sun, Rui; Zeng, Benhua; Wei, Hong; Tian, Zhigang; Wei, Haiming","year":2018,"journal":"Frontiers in immunology, 9, 1065","doi":"10.3389/fimmu.2018.01065","pmid":"29868024","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03613","title":"Neuropeptide Initiated Mast Cell Activation by Transcutaneous Electrical Acupoint Stimulation of Acupoint LI4 in Rats.","authors":"Chen, Li-Zhen; Kan, Yu; Zhang, Zhi-Yun; Wang, Yi-Li; Zhang, Xiao-Ning; Wang, Xiao-Yu; He, Wei; Jing, Xiang-Hong","year":2018,"journal":"Scientific reports, 8(1), 13921","doi":"10.1038/s41598-018-32048-3","pmid":"30224712","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03614","title":"Mechanisms of μ-opioid receptor inhibition of NMDA receptor-induced substance P release in the rat spinal cord.","authors":"Chen, Wenling; Ennes, Helena S; McRoberts, James A; Marvizón, Juan Carlos","year":2018,"journal":"Neuropharmacology, 128, 255-268","doi":"10.1016/j.neuropharm.2017.10.014","pmid":"29042318","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03615","title":"Roles and Mechanisms of Human Cathelicidin LL-37 in Cancer.","authors":"Chen, Xi; Zou, Xianqiong; Qi, Guangying; Tang, Ying; Guo, Yong; Si, Jia; Liang, Lihua","year":2018,"journal":"Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 47(3), 1060-1073","doi":"10.1159/000490183","pmid":"29843147","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03616","title":"Tuft cells: Distribution and connections with nerves and endocrine cells in mouse intestine.","authors":"Cheng, Xiaowen; Voss, Ulrikke; Ekblad, Eva","year":2018,"journal":"Experimental cell research, 369(1), 105-111","doi":"10.1016/j.yexcr.2018.05.011","pmid":"29758188","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03617","title":"A canine keratinocyte cell line expresses antimicrobial peptide and cytokine genes upon stimulation with bacteria, microbial ligands and recombinant cytokines.","authors":"Chermprapai, Suttiwee; Broere, Femke; Schlotter, Yvette M; Veldhuizen, Edwin J A; Rutten, Victor P M G","year":2018,"journal":"Veterinary immunology and immunopathology, 206, 35-40","doi":"10.1016/j.vetimm.2018.11.009","pmid":"30502910","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03618","title":"Antimicrobial Peptide Resistance Mechanism Contributes to Staphylococcus aureus Infection.","authors":"Cheung, Gordon Y C; Fisher, Emilie L; McCausland, Joshua W; Choi, Justin; Collins, John W M; Dickey, Seth W; Otto, Michael","year":2018,"journal":"The Journal of infectious diseases, 217(7), 1153-1159","doi":"10.1093/infdis/jiy024","pmid":"29351622","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The S. aureus Pmt ABC transporter defends bacteria from killing by important human AMPs and from elimination by human neutrophils. Pmt contributes to virulence during skin infection in an AMP-dependent manner — when AMP activity was removed from the experimental system, the virulence advantage of Pmt was eliminated. This provides the first direct in vivo evidence that antimicrobial peptide resistance per se is important during bacterial infection, not just in laboratory conditions.","whyItMatters":"Antimicrobial peptides are frequently proposed as alternatives to conventional antibiotics, but a major concern has been whether bacteria could evolve resistance that undermines their therapeutic potential. This study shows that AMP resistance mechanisms not only exist but are already clinically important — S. aureus uses them to cause infections. This has implications for both understanding staph pathogenesis and designing AMP-based therapies that can overcome resistance.","specificNumbers":"","methodology":"Researchers compared wild-type S. aureus to Pmt-deficient mutants for: susceptibility to human AMPs (in vitro killing assays), survival against human neutrophils, and virulence in mouse skin infection models. To prove the effect was specifically AMP-dependent, they performed skin infections under conditions where AMP activity was absent, showing that the virulence advantage of Pmt disappeared — confirming the causal link between AMP resistance and infection outcome.","limitations":"The study focused on one resistance mechanism (Pmt transporter) in one bacterial species (S. aureus) during one type of infection (skin). Other AMP resistance mechanisms may operate differently. The mouse skin infection model may not fully represent the complexity of human staph infections. The specific AMPs involved in the Pmt-dependent virulence were not individually identified. Whether Pmt-mediated resistance could be overcome by modified AMPs was not tested."},{"rthcId":"RPEP-03619","title":"Substance P Regulation in Epilepsy.","authors":"Chi, Guangfan; Huang, Zhehao; Li, Xianglan; Zhang, Kun; Li, Guangquan","year":2018,"journal":"Current neuropharmacology, 16(1), 43-50","doi":"10.2174/1570159X15666170504122410","pmid":"28474564","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03620","title":"Manifestation of atopic dermatitis-like skin in TNCB-induced NC/Nga mice is ameliorated by topical treatment of substance P, possibly through blockade of allergic inflammation.","authors":"Choi, Hyeongwon; Kim, Dong-Jin; Nam, Seungwoo; Lim, Sunki; Hwang, Jae-Sung; Park, Ki Sook; Hong, Hyun Sook; Shin, Min Kyung; Chung, Eunkyung; Son, Youngsook","year":2018,"journal":"Experimental dermatology, 27(4), 396-402","doi":"10.1111/exd.13421","pmid":"28833499","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03621","title":"Substance P Receptor in the Rat Heart and Regulation of Its Expression in Long-Term Diabetes.","authors":"Chottova Dvorakova, Magdalena; Mistrova, Eliska; Paddenberg, Renate; Kummer, Wolfgang; Slavikova, Jana","year":2018,"journal":"Frontiers in physiology, 9, 918","doi":"10.3389/fphys.2018.00918","pmid":"30057556","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"NK1R protein was localized by immunofluorescence to the surface of some intracardiac neurons and smooth muscle cells of coronary vessels. Quantitative RT-PCR showed NK1R mRNA was present in all four heart chambers, with the highest levels in the left atrium.\n\nLaser capture microdissection revealed NK1R mRNA in some intracardiac neurons but not in cardiomyocytes or coronary smooth muscle cells, suggesting post-transcriptional regulation in smooth muscle cells.\n\nIn long-term diabetes (53 weeks post-induction), NK1R mRNA was significantly downregulated in the right atrium and upregulated in the right ventricle, indicating chamber-specific dysregulation of neuropeptide receptor expression in diabetic cardiomyopathy.","whyItMatters":"Diabetic cardiomyopathy is a major cause of heart failure in diabetes patients, and its mechanisms are incompletely understood. The finding that diabetes alters substance P receptor expression in specific heart chambers suggests that disrupted neuropeptide signaling may contribute to diabetic heart disease. Understanding these molecular changes could identify new therapeutic targets for preventing or treating cardiac complications of diabetes.","specificNumbers":"","methodology":"The researchers used multiple techniques to characterize NK1R in the rat heart: western blot to detect NK1R protein in separate heart compartments, immunofluorescence with peptide preabsorption controls for tissue localization, quantitative RT-PCR for mRNA abundance across heart chambers, and laser capture microdissection to isolate and test specific cell types (neurons, cardiomyocytes, smooth muscle cells). Long-term diabetic rats were studied at 53 weeks post-diabetes induction.","limitations":"This is a rat study, and the findings may not directly translate to human hearts. The sample sizes for laser capture microdissection experiments are not specified, and NK1R mRNA was only detected in 'some samples' of intracardiac neurons. The study only examined one timepoint in diabetes (53 weeks), so the temporal progression of receptor changes is unknown. The functional consequences of the observed NK1R expression changes were not tested."},{"rthcId":"RPEP-03622","title":"Functionalized PVA-silk blended nanofibrous mats promote diabetic wound healing via regulation of extracellular matrix and tissue remodelling.","authors":"Chouhan, Dimple; Janani, G; Chakraborty, Bijayashree; Nandi, Samit K; Mandal, Biman B","year":2018,"journal":"Journal of tissue engineering and regenerative medicine, 12(3), e1559-e1570","doi":"10.1002/term.2581","pmid":"28987032","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Non-mulberry silk fibroin (NMSF)-based nanofibrous dressings functionalized with LL-37 antimicrobial peptide and growth factors significantly outperformed mulberry silk (Bombyx mori), PVA, and control dressings for diabetic wound healing (P<0.01 at 14 days).\n\nNMSF dressings demonstrated faster granulation tissue development, angiogenesis (blood vessel formation), and re-epithelialization. Gene expression analysis showed higher matrix metalloproteinase activity and collagen protein expression, indicating enhanced tissue remodeling. At 4 weeks, NMSF-treated wounds showed organized extracellular matrix deposition (collagen types I and III, elastin, reticulin) and higher wound breaking strength compared to all other groups. The non-mulberry silk's inherent RGD cell-binding motifs enhanced cell-material interactions.","whyItMatters":"Diabetic foot ulcers affect approximately 15-25% of diabetes patients during their lifetime and are a leading cause of non-traumatic limb amputation. Current wound dressings are largely passive. A bioactive dressing that simultaneously delivers antimicrobial peptides (preventing infection) and growth factors (promoting healing) from a natural silk matrix addresses multiple failure points in diabetic wound healing. LL-37 is particularly attractive because it's the only cathelicidin antimicrobial peptide produced by humans, making it intrinsically biocompatible.","specificNumbers":"","methodology":"Electrospun nanofibrous mats were fabricated from PVA blended with silk fibroin from mulberry (Bombyx mori) and non-mulberry silkworms. Mats were functionalized with growth factors and LL-37 antimicrobial peptide for sustained delivery. Diabetic rabbit models were created using alloxan induction. Wounds were treated for 14 days and followed for 4 weeks. Outcomes included wound closure, histopathology, angiogenesis, re-epithelialization, gene expression (MMPs, collagen), extracellular matrix composition, and wound breaking strength.","limitations":"The study used an alloxan-induced diabetic rabbit model, which may not fully replicate the complexity of human diabetic wounds (chronic inflammation, neuropathy, vascular disease). The sample size of rabbits is not specified in the abstract. The 4-week follow-up is relatively short for assessing long-term wound remodeling outcomes. Manufacturing scalability and cost of functionalized silk nanofiber dressings were not addressed. The relative contributions of LL-37, growth factors, and the silk matrix itself to wound healing were not individually quantified."},{"rthcId":"RPEP-03623","title":"The impact of short-chain fatty acids on GLP-1 and PYY secretion from the isolated perfused rat colon.","authors":"Christiansen, Charlotte Bayer; Gabe, Maria Buur Nordskov; Svendsen, Berit; Dragsted, Lars Ove; Rosenkilde, Mette Marie; Holst, Jens Juul","year":2018,"journal":"American journal of physiology. Gastrointestinal and liver physiology, 315(1), G53-G65","doi":"10.1152/ajpgi.00346.2017","pmid":"29494208","tags":["glp-1-agonists","gut-microbiome","gastrointestinal-peptides"],"studyType":"animal","evidenceStrength":"strong","keyFinding":"Using an isolated perfused rat colon, the researchers found that luminal and especially vascular infusion of acetate and butyrate significantly increased GLP-1 secretion, with a smaller effect on PYY secretion (but only after intracellular cAMP was enhanced). Propionate had no effect on either hormone.\n\nCritically, the study showed this effect does NOT work through the FFAR2 and FFAR3 fatty acid receptors, as widely assumed. A specific FFAR2/FFAR3 agonist (CFMB/AR420626) had no effect on GLP-1 output, and a FFAR3 antagonist didn't block the SCFA-induced response. Instead, blocking voltage-gated calcium channels (nifedipine), opening KATP channels (diazoxide), or inhibiting ATP synthesis (2,4-DNP) completely abolished the responses — indicating SCFAs are metabolized as an energy source by colonocytes, and it's this metabolic process that drives GLP-1 secretion.","whyItMatters":"This study challenges a widely held assumption in gut biology. Many researchers and supplement companies have promoted the idea that fiber and SCFAs boost GLP-1 through FFAR2/FFAR3 receptors. If the real mechanism is metabolic — SCFAs serving as fuel for colon cells — it changes how we think about designing dietary interventions, prebiotics, and microbiome therapies aimed at enhancing natural GLP-1 release. It also suggests that the specific type of SCFA matters: acetate and butyrate work, but propionate does not.","specificNumbers":"Acetate and butyrate increase GLP-1 secretion · Propionate has no effect · FFAR2/FFAR3 receptors not involved · CFMB ~750x more potent than SCFAs at FFAR2 · Nifedipine, diazoxide, and 2,4-DNP abolished responses","methodology":"The researchers used isolated perfused rat colons — an ex vivo preparation that preserves the colon's blood supply, nerve connections, and cellular architecture while allowing precise control over what the colon is exposed to. They infused SCFAs (acetate, propionate, butyrate) both luminally (from the gut side) and vascularly (through the blood supply) and measured GLP-1 and PYY secretion. They then used receptor-specific agonists, antagonists, ion channel blockers, and metabolic inhibitors to determine the exact mechanism driving hormone release.","limitations":"This is an ex vivo rat colon study, which may not perfectly represent the intact human colon with its full complement of neural, hormonal, and immune inputs. The isolated preparation, while excellent for mechanistic studies, removes some physiological context. Results in rats may not directly translate to humans. The PYY response to SCFAs was only observed after cAMP enhancement, suggesting the baseline effect may be weaker than the GLP-1 response."},{"rthcId":"RPEP-03624","title":"Group A Streptococcus Prevents Mast Cell Degranulation to Promote Extracellular Trap Formation.","authors":"Clark, Mary; Kim, Jessica; Etesami, Neelou; Shimamoto, Jacqueline; Whalen, Ryan V; Martin, Gary; Okumura, Cheryl Y M","year":2018,"journal":"Frontiers in immunology, 9, 327","doi":"10.3389/fimmu.2018.00327","pmid":"29535718","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03625","title":"Neuropeptide S in the basolateral amygdala mediates an adaptive behavioral stress response in a rat model of posttraumatic stress disorder by increasing the expression of BDNF and the neuropeptide YY1 receptor.","authors":"Cohen, Hagit; Vainer, Ella; Zeev, Kaplan; Zohar, Joseph; Mathé, Aleksander A","year":2018,"journal":"European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 28(1), 159-170","doi":"10.1016/j.euroneuro.2017.11.006","pmid":"29157796","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Microinfusion of NPS into the basolateral amygdala (BLA) one hour after predator-scent stress exposure completely abolished the extreme behavioral response in a rat PTSD model. This single treatment restored decreased hippocampal expression of BDNF and, unexpectedly, NPY-Y1 receptor (NPY-Y1R) — though it did not affect decreased NPY expression itself.\n\nCritically, administering both an NPY-Y1R antagonist and an NPS receptor antagonist together had an additive effect that completely prevented NPS's anxiolytic effects and disrupted NPY-Y1R expression. This reveals that NPS acts through both its own receptor and the NPY-Y1R system, and that crosstalk between these two neuropeptide pathways is necessary for the stress-protective effect.","whyItMatters":"PTSD affects millions of people and current treatments often fall short. This study identifies neuropeptide S as a potential early-intervention target — a single dose given shortly after trauma could prevent PTSD from developing. The unexpected discovery that NPS works through the NPY system creates a mechanistic bridge between two major anxiety-regulating peptide pathways, potentially opening dual-target therapeutic strategies.","specificNumbers":"","methodology":"Rats were exposed to predator-scent stress (PSS) as a PTSD model, then received microinjections of NPS into the basolateral amygdala 1 hour post-exposure. Behavioral testing assessed anxiety responses long-term. Molecular analyses measured hippocampal expression of NPY, NPY-Y1R, and BDNF. Receptor antagonist experiments (NPS-RA and NPY-Y1RA, alone and combined) dissected the mechanism. Circulating corticosterone was measured at multiple time points.","limitations":"The study was conducted in male rats using a predator-scent stress model, which may not fully capture human PTSD. Direct brain microinjection is not a feasible delivery method in humans. The long-term durability of the protective effect was not fully characterized. Female rats were not included, despite known sex differences in PTSD prevalence and neuropeptide biology."},{"rthcId":"RPEP-03626","title":"Synthetic Cancer-Targeting Innate Immune Stimulators Give Insights into Avidity Effects.","authors":"Conibear, Anne C; Pötgens, André J G; Thewes, Karine; Altdorf, Claudia; Hilzendeger, Clarissa; Becker, Christian F W","year":2018,"journal":"Chembiochem : a European journal of chemical biology, 19(5), 459-469","doi":"10.1002/cbic.201700522","pmid":"29230922","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Using solid-phase peptide synthesis and chemoselective ligations, researchers constructed a series of targeted immune system engagers (ISErs) bearing different numbers and combinations of: two cancer-targeting 'binder' peptides (targeting ephrin A2 and integrin α3 receptors) and one immune-stimulating 'effector' peptide (targeting formyl peptide receptors). The study demonstrated that multivalency and receptor density significantly influence avidity effects — binding strength increased with more binding moieties. Both cancer cell binding and immune cell stimulation activities were characterized across the constructs.","whyItMatters":"Most bispecific and multivalent cancer immunotherapies rely on complex and expensive recombinant antibody production. Peptide-based approaches are simpler to manufacture, more modular, and allow systematic optimization. By engaging both the cancer cell and the immune system with a single synthetic molecule, these ISErs represent a new class of potential cancer therapeutics that could be more accessible and customizable.","specificNumbers":"","methodology":"Peptide building blocks were synthesized using solid-phase peptide synthesis and assembled into multivalent/multispecific constructs via chemoselective ligation chemistry. Cancer cell binding was measured against ephrin A2 and integrin α3-expressing tumor cell lines. Immune cell stimulation was assessed through formyl peptide receptor activation of innate immune cells. Various architectures were compared to understand avidity effects.","limitations":"This is an in vitro study without animal models or clinical data. The peptide constructs' in vivo stability, biodistribution, and pharmacokinetics were not assessed. Cancer cell binding and immune stimulation were measured separately — synergistic anti-tumor effects were not demonstrated in a model system. The specific peptide targets (ephrin A2, integrin α3) may have limited specificity for some tumor types. Manufacturing scalability was not addressed."},{"rthcId":"RPEP-03627","title":"Endogenous and Exogenous Opioids in Pain.","authors":"Corder, Gregory; Castro, Daniel C; Bruchas, Michael R; Scherrer, Grégory","year":2018,"journal":"Annual review of neuroscience, 41, 453-473","doi":"10.1146/annurev-neuro-080317-061522","pmid":"29852083","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03628","title":"Intracellular oligonucleotide delivery using the cell penetrating peptide Xentry.","authors":"Coutinho, Frazer P; Green, Colin R; Rupenthal, Ilva D","year":2018,"journal":"Scientific reports, 8(1), 11256","doi":"10.1038/s41598-018-29556-7","pmid":"30050146","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03629","title":"Impact of weight loss achieved through a multidisciplinary intervention on appetite in patients with severe obesity.","authors":"Coutinho, S R; Rehfeld, J F; Holst, J J; Kulseng, B; Martins, C","year":2018,"journal":"American journal of physiology. Endocrinology and metabolism, 315(1), E91-E98","doi":"10.1152/ajpendo.00322.2017","pmid":"29360396","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03630","title":"Novel BUF2-magnetite nanobioconjugates with cell-penetrating abilities.","authors":"Cuellar, Monica; Cifuentes, Javier; Perez, Jessica; Suarez-Arnedo, Alejandra; Serna, Julian A; Groot, Helena; Muñoz-Camargo, Carolina; Cruz, Juan C","year":2018,"journal":"International journal of nanomedicine, 13, 8087-8094","doi":"10.2147/IJN.S188074","pmid":"30568447","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BUF2-magnetite nanobioconjugates demonstrated cell-penetrating ability in both bacterial and mammalian cells, with intracellular uptake confirmed in THP-1 human monocyte cells for the first time. The conjugates were biocompatible and did not cause significant cell toxicity. However, the conjugation to nanoparticles abolished BUF2's native antimicrobial activity, indicating that direct surface attachment constrains the peptide's functional conformation.","whyItMatters":"Targeted drug delivery remains one of pharmacology's biggest challenges — getting therapeutic molecules to the right cells without harming the rest of the body. This study demonstrates that cell-penetrating peptides can be combined with magnetic nanoparticles to create delivery vehicles that enter cells effectively. The magnetic component also opens possibilities for magnetically guided targeting. The loss of antimicrobial activity highlights an important design consideration for future peptide-nanoparticle conjugates.","specificNumbers":"","methodology":"Researchers conjugated buforin II (BUF2) peptide to magnetite (iron oxide) nanoparticles and characterized the resulting nanobioconjugates using Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), and thermogravimetric analysis (TGA). They assessed biocompatibility and tested cell penetration in both bacterial cells and mammalian THP-1 monocyte cells. Antimicrobial activity was evaluated through standard microbial sensitivity tests.","limitations":"The conjugates lost their antimicrobial activity when the peptide was directly attached to the nanoparticle surface, which is a significant functional limitation. The study was entirely in vitro — no animal studies were conducted. The researchers did not test actual therapeutic cargo delivery. The hypothesis that a flexible linker would restore activity was proposed but not tested in this study."},{"rthcId":"RPEP-03631","title":"Growth hormone-releasing hormone (GHRH) and its agonists inhibit hepatic and tumoral secretion of IGF-1.","authors":"Cui, Tengjiao; Schally, Andrew V","year":2018,"journal":"Oncotarget, 9(47), 28745-28756","doi":"10.18632/oncotarget.25676","pmid":"29983893","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03632","title":"Characterization of Stress and Innate Immunity Resistance of Wild-Type and Δp66 Borrelia burgdorferi.","authors":"Curtis, Michael W; Hahn, Beth L; Zhang, Kai; Li, Chunhao; Robinson, Richard T; Coburn, Jenifer","year":2018,"journal":"Infection and immunity, 86(2)","doi":"10.1128/IAI.00186-17","pmid":"29158430","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03633","title":"Daily oral supplementation with collagen peptides combined with vitamins and other bioactive compounds improves skin elasticity and has a beneficial effect on joint and general wellbeing.","authors":"Czajka, Anna; Kania, Ewa M; Genovese, Licia; Corbo, Andrea; Merone, Giovanni; Luci, Cecilia; Sibilla, Sara","year":2018,"journal":"Nutrition research (New York, N.Y.), 57, 97-108","doi":"10.1016/j.nutres.2018.06.001","pmid":"30122200","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In a 90-day double-blind, placebo-controlled trial of 120 subjects, daily oral supplementation with a liquid nutraceutical containing hydrolyzed fish collagen peptides, vitamins, antioxidants, and other ingredients produced a 40% increase in skin elasticity (p < .0001) versus placebo. Histological analysis of skin biopsies showed reduced solar elastosis and improved collagen fiber organization. Joint pain decreased by 43% and joint mobility improved by 39%. Self-perception questionnaires confirmed subjects felt more hydrated and elastic skin.","whyItMatters":"This is one of the few collagen peptide studies that includes histological evidence from skin biopsies in addition to clinical measurements and patient-reported outcomes. The combination of objective tissue-level changes and significant functional improvements in both skin and joints provides stronger evidence for collagen peptide supplementation than studies relying on subjective assessments alone.","specificNumbers":"","methodology":"Double-blind, randomized, placebo-controlled clinical trial with 120 subjects consuming either the test product (containing hydrolyzed fish collagen, chondroitin sulfate, glucosamine, L-carnitine, vitamins, and minerals) or placebo daily for 90 days. Outcomes included instrumental measurement of skin elasticity, histological analysis of skin biopsies (assessing solar elastosis and collagen fiber organization), joint pain and mobility assessments, and self-perception questionnaires.","limitations":"The test product contains multiple active ingredients (collagen peptides, chondroitin sulfate, glucosamine, L-carnitine, vitamins, minerals, antioxidants), making it impossible to attribute the results specifically to collagen peptides alone. The 90-day duration is relatively short for assessing anti-aging effects. The study does not report long-term follow-up or whether benefits persist after discontinuation. The specific doses of each ingredient are not detailed in the abstract."},{"rthcId":"RPEP-03634","title":"Neonatal Oxytocin Treatment Ameliorates Autistic-Like Behaviors and Oxytocin Deficiency in Valproic Acid-Induced Rat Model of Autism.","authors":"Dai, Yu-Chuan; Zhang, Hong-Feng; Schön, Michael; Böckers, Tobias M; Han, Song-Ping; Han, Ji-Sheng; Zhang, Rong","year":2018,"journal":"Frontiers in cellular neuroscience, 12, 355","doi":"10.3389/fncel.2018.00355","pmid":"30356897","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Adolescent VPA rats showed lower OXT mRNA levels, fewer oxytocin-immunoreactive (OXT-ir) cells in the hypothalamus, and reduced oxytocin concentrations in cerebrospinal fluid compared to controls. The oxytocin deficit was already present in neonatal VPA rats, with fewer OXT-ir cells in the supraoptic nucleus.\n\nAcute intranasal oxytocin administration restored social preference in adolescent VPA rats, demonstrating immediate therapeutic potential.\n\nCritically, early postnatal oxytocin treatment produced long-term effects: social impairments and repetitive behaviors were ameliorated through adolescence, and this behavioral improvement was accompanied by an increase in OXT-ir cells in the brain. This suggests early oxytocin intervention may have a developmental window of opportunity with lasting therapeutic benefits.","whyItMatters":"Oxytocin has been one of the most discussed potential treatments for autism spectrum disorder, but clinical results have been mixed. This study provides important mechanistic evidence that autism may involve a fundamental oxytocin deficiency in the brain, and that early intervention — during a critical developmental window — could have lasting benefits that extend well beyond the treatment period. This supports the concept that timing of intervention matters enormously.","specificNumbers":"","methodology":"Researchers used the valproic acid (VPA) rat model of autism, where prenatal VPA exposure produces offspring with autism-like behaviors. They measured oxytocin mRNA levels, counted oxytocin-immunoreactive cells in the hypothalamus, and measured oxytocin in cerebrospinal fluid. Behavioral testing assessed social preference and repetitive behaviors. Two treatment approaches were tested: acute intranasal oxytocin in adolescent rats, and early postnatal oxytocin treatment with behavioral follow-up into adolescence.","limitations":"This is an animal study using a pharmacological model of autism (VPA exposure), which does not capture the full genetic complexity of human autism spectrum disorder. Results in rats may not translate directly to humans. The study does not detail specific doses, treatment schedules, or group sizes in the abstract. Long-term safety of neonatal oxytocin exposure is not addressed. The VPA model represents only one of many potential etiologies of autism."},{"rthcId":"RPEP-03635","title":"Rational Design, Synthesis, and Pharmacological Characterization of Novel Ghrelin Receptor Inverse Agonists as Potential Treatment against Obesity-Related Metabolic Diseases.","authors":"Daina, Antoine; Giuliano, Claudio; Pietra, Claudio; Wang, Junbo; Chi, Yushi; Zou, Zack; Li, Fugang; Yan, Zhonghua; Zhou, Yifan; Guainazzi, Angelo; Garcia Rubio, Silvina; Zoete, Vincent","year":2018,"journal":"Journal of medicinal chemistry, 61(24), 11039-11060","doi":"10.1021/acs.jmedchem.8b00794","pmid":"30265805","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03636","title":"Host-parasite Responses Outcome Regulate the Expression of Antimicrobial Peptide Genes in the Skin of BALB/c and C57BL/6 Murine Strains Following Leishmania major MRHO/IR/75/ER Infection.","authors":"Daneshvar, Hamid; Tavakoli Kareshk, Amir; Sharifi, Iraj; Keyhani, Alireza; Tavakoli Oliaee, Razieh; Asadi, Arash","year":2018,"journal":"Iranian journal of parasitology, 13(4), 515-523","doi":null,"pmid":"30697304","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Paradoxically, BALB/c mice (the Leishmania-susceptible strain) showed significantly higher expression of all tested antimicrobial peptide genes (mBD-1, mBD-2, mBD-3, mBD-4, mBD-6, and CRAMP) compared to C57BL/6 mice (the resistant strain). Despite this higher AMP expression, BALB/c mice still developed cutaneous leishmaniasis.\n\nThe cytokine profiles confirmed expected immune responses: susceptible BALB/c mice had elevated IL-10 (anti-inflammatory) and reduced IL-12, while resistant C57BL/6 mice showed the opposite pattern. This demonstrates that elevated antimicrobial peptide expression alone cannot overcome Leishmania infection when the broader immune response is skewed toward susceptibility.","whyItMatters":"Antimicrobial peptides like defensins and cathelicidins are often assumed to provide direct protection against pathogens. This study challenges that assumption for parasitic infections: the most susceptible mice actually produced more AMPs, yet still got sicker. This reveals important limitations of antimicrobial peptides against intracellular parasites like Leishmania and underscores that peptide-based innate immunity is necessary but not sufficient without proper adaptive immune support.","specificNumbers":"6 AMP genes tested (mBD-1, -2, -3, -4, -6, CRAMP) · All upregulated in susceptible BALB/c · 2 mouse strains compared · 3 time points (1, 3, 7 days PI) · 5×10⁶ parasites/ml inoculum","methodology":"BALB/c (susceptible) and C57BL/6 (resistant) mice were subcutaneously infected with L. major promastigotes (5×10⁶/ml). Skin samples were collected at 1, 3, and 7 days post-infection. mRNA levels of six antimicrobial peptide genes (mBD-1 through mBD-6 and CRAMP), IL-10, IL-12, and parasite load were measured using standard molecular methods.","limitations":"The study measured mRNA expression but not protein levels or antimicrobial activity of the peptides in the skin. The early time points (1-7 days) may not capture the full immune response timeline. The study does not determine whether the elevated AMP expression in susceptible mice is a cause, consequence, or compensatory response to higher parasite burden. Only one Leishmania strain was tested."},{"rthcId":"RPEP-03637","title":"Ginsenoside Re protects methamphetamine-induced dopaminergic neurotoxicity in mice via upregulation of dynorphin-mediated κ-opioid receptor and downregulation of substance P-mediated neurokinin 1 receptor.","authors":"Dang, Duy-Khanh; Shin, Eun-Joo; Kim, Dae-Joong; Tran, Hai-Quyen; Jeong, Ji Hoon; Jang, Choon-Gon; Nah, Seung-Yeol; Jeong, Jung Hwan; Byun, Jae Kyung; Ko, Sung Kwon; Bing, Guoying; Hong, Jau-Shyong; Kim, Hyoung-Chun","year":2018,"journal":"Journal of neuroinflammation, 15(1), 52","doi":"10.1186/s12974-018-1087-7","pmid":"29467000","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03638","title":"Long-term follow up of metastatic melanoma patients treated with Thymosin alpha-1: investigating immune checkpoints synergy.","authors":"Danielli, Riccardo; Cisternino, Filomena; Giannarelli, Diana; Calabrò, Luana; Camerini, Roberto; Savelli, Vinno; Bova, Giovanni; Dragonetti, Rosella; Di Giacomo, Anna Maria; Altomonte, Maresa; Maio, Michele","year":2018,"journal":"Expert opinion on biological therapy, 18(sup1), 77-83","doi":"10.1080/14712598.2018.1494717","pmid":"30063847","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03639","title":"Antibiotics-Peptide Conjugates Against Multidrug-resistant Bacterial Pathogens.","authors":"David, Akinwale Ajayi; Park, Shang Eun; Parang, Keykavous; Tiwari, Rakesh Kumar","year":2018,"journal":"Current topics in medicinal chemistry, 18(22), 1926-1936","doi":"10.2174/1568026619666181129141524","pmid":"30499392","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Antibiotic-peptide conjugates (APCs) combine known antibiotics with antimicrobial, cell-penetrating, or membrane-active peptides via chemical linkers. The strategy targets multiple bacterial resistance mechanisms simultaneously: efflux pump activation (which reduces intracellular antibiotic concentrations), target site protection proteins, and mutations in DNA/topoisomerase genes that alter binding sites.\n\nThe conjugation approach aims to produce synergistic antibacterial activity while mitigating individual limitations — improving cellular penetration of antibiotics while reducing the serum instability, cytotoxicity, hemolysis, and salt sensitivity that limit standalone antimicrobial peptides.","whyItMatters":"Antimicrobial resistance kills over a million people annually and is projected to worsen. Rather than waiting years for entirely new antibiotic classes, APCs offer a faster path by enhancing existing drugs. This hybrid approach could extend the useful life of current antibiotics and provide new treatment options for infections caused by MRSA, multidrug-resistant gram-negative bacteria, and other superbugs.","specificNumbers":"","methodology":"This is a narrative review article surveying published literature on antibiotic-peptide conjugate strategies, including their design rationale, linker chemistry, physicochemical properties, and antibacterial efficacy data against multidrug-resistant pathogens.","limitations":"As a review, this article does not present new experimental data. Many APCs described are at early preclinical stages, and challenges around manufacturing scale-up, in vivo pharmacokinetics, and regulatory pathways for hybrid molecules are not fully addressed. The review was published in 2018, so newer APC developments may not be covered."},{"rthcId":"RPEP-03640","title":"Investigation of the effect of homocysteinylation of substance P on its binding to the NK1 receptor using molecular dynamics simulation.","authors":"Davoudmanesh, Samira; Mosaabadi, Jafar Mohammadian","year":2018,"journal":"Journal of molecular modeling, 24(7), 177","doi":"10.1007/s00894-018-3695-7","pmid":"29943287","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03641","title":"PANCOSMA COMPARATIVE GUT PHYSIOLOGY SYMPOSIUM: ALL ABOUT APPETITE REGULATION: Effects of diet and gonadal steroids on appetite regulation and food intake of companion animals.","authors":"de Godoy, Maria R C","year":2018,"journal":"Journal of animal science, 96(8), 3526-3536","doi":"10.1093/jas/sky146","pmid":"29982536","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03642","title":"Peptide degradation and the role of DPP-4 inhibitors in the treatment of type 2 diabetes.","authors":"Deacon, Carolyn F","year":2018,"journal":"Peptides, 100, 150-157","doi":"10.1016/j.peptides.2017.10.011","pmid":"29412814","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03643","title":"The CRF Family of Neuropeptides and their Receptors - Mediators of the Central Stress Response.","authors":"Dedic, Nina; Chen, Alon; Deussing, Jan M","year":2018,"journal":"Current molecular pharmacology, 11(1), 4-31","doi":"10.2174/1874467210666170302104053","pmid":"28260504","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03644","title":"Up-Regulation of Antimicrobial Peptides Gallerimycin and Galiomicin in Galleria mellonella Infected with Candida Yeasts Displaying Different Virulence Traits.","authors":"Dekkerová-Chupáčová, Jaroslava; Borghi, Elisa; Morace, Giulia; Bujdáková, Helena","year":2018,"journal":"Mycopathologia, 183(6), 935-940","doi":"10.1007/s11046-018-0300-7","pmid":"30386966","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03645","title":"Cell penetrating peptides: A concise review with emphasis on biomedical applications.","authors":"Derakhshankhah, Hossein; Jafari, Samira","year":2018,"journal":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 108, 1090-1096","doi":"10.1016/j.biopha.2018.09.097","pmid":"30372809","tags":["cell-penetrating-peptides","peptide-delivery"],"studyType":"Review","evidenceStrength":"moderate","keyFinding":"Cell penetrating peptides (CPPs) are short peptide sequences that can cross cell membranes — a feat that most therapeutic molecules cannot accomplish. This review classifies CPPs into categories based on their origin and properties, describes their uptake mechanisms (direct penetration vs. endocytosis), and catalogs their biomedical applications as delivery vehicles for nucleic acids, proteins, siRNA, drugs, and nanoparticles.\n\nThe key insight is that CPPs can carry virtually any type of therapeutic cargo across cell membranes, making them one of the most versatile drug delivery tools in biomedical research.","whyItMatters":"Getting drugs inside cells is one of the biggest challenges in medicine. Many promising therapeutics — gene therapies, siRNA, proteins — can't cross cell membranes to reach their targets. CPPs solve this problem by acting as molecular taxis, ferrying cargo through the membrane barrier. This technology underpins a wide range of emerging therapies from cancer treatment to gene editing.","specificNumbers":"Review covering 20+ years of CPP research · cargo types: nucleic acids, proteins, siRNA, drugs, nanoparticles · multiple CPP classes and uptake mechanisms reviewed","methodology":"Narrative review synthesizing the CPP literature. The authors describe CPP classification schemes (cationic, amphipathic, hydrophobic), uptake mechanisms (direct penetration, endocytosis-dependent pathways), and biomedical applications across drug delivery, gene therapy, and diagnostic imaging.","limitations":"As a concise review, it doesn't cover all CPPs or applications exhaustively. The review primarily describes in vitro and preclinical evidence — few CPP-based therapeutics have reached clinical approval. Endosomal entrapment (where cargo gets stuck after uptake) is a major unresolved challenge that is not deeply explored. The review is from 2018 and doesn't capture more recent developments."},{"rthcId":"RPEP-03646","title":"EPR monitoring of wound oxygenation as a biomarker of response to gene therapy encoding hCAP-18/LL37 peptide.","authors":"Desmet, Céline M; Vandermeulen, Gaëlle; Bouzin, Caroline; Lam, Martin C; Préat, Véronique; Levêque, Philippe; Gallez, Bernard","year":2018,"journal":"Magnetic resonance in medicine, 79(6), 3267-3273","doi":"10.1002/mrm.26956","pmid":"28983954","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03647","title":"Heparin assisted assembly of somatostatin amyloid nanofibrils results in disordered precipitates by hindrance of protofilaments interactions.","authors":"Dharmadana, Durga; Reynolds, Nicholas P; Dekiwadia, Chaitali; Conn, Charlotte E; Valéry, Céline","year":2018,"journal":"Nanoscale, 10(38), 18195-18204","doi":"10.1039/c8nr02159g","pmid":"30141801","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03648","title":"Neuropeptide Y and its Involvement in Chronic Pain.","authors":"Diaz-delCastillo, Marta; Woldbye, David P D; Heegaard, Anne Marie","year":2018,"journal":"Neuroscience, 387, 162-169","doi":"10.1016/j.neuroscience.2017.08.050","pmid":"28890052","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03649","title":"Dermatologic toxicity from novel therapy using antimicrobial peptide LL-37 in melanoma: A detailed examination of the clinicopathologic features.","authors":"Dolkar, Tsetan; Trinidad, Celestine M; Nelson, Kelly C; Amaria, Rodabe N; Nagarajan, Priyadharsini; Torres-Cabala, Carlos A; Ivan, Doina; Prieto, Victor G; Tetzlaff, Michael T; Curry, Jonathan L; Aung, Phyu P","year":2018,"journal":"Journal of cutaneous pathology, 45(7), 539-544","doi":"10.1111/cup.13262","pmid":"29665030","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03650","title":"Electron transfer dissociation of synthetic and natural peptides containing lanthionine/methyllanthionine bridges.","authors":"Dolle, Ashwini B; Jagadeesh, Narasimhappagari; Bhaumik, Suman; Prakash, Sunita; Biswal, Himansu S; Gowd, Konkallu Hanumae","year":2018,"journal":"Rapid communications in mass spectrometry : RCM, 32(11), 831-843","doi":"10.1002/rcm.8108","pmid":"29520895","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03651","title":"Optimized Peptide-MHC Multimer Protocols for Detection and Isolation of Autoimmune T-Cells.","authors":"Dolton, Garry; Zervoudi, Efthalia; Rius, Cristina; Wall, Aaron; Thomas, Hannah L; Fuller, Anna; Yeo, Lorraine; Legut, Mateusz; Wheeler, Sophie; Attaf, Meriem; Chudakov, Dmitriy M; Choy, Ernest; Peakman, Mark; Sewell, Andrew K","year":2018,"journal":"Frontiers in immunology, 9, 1378","doi":"10.3389/fimmu.2018.01378","pmid":"30008714","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03652","title":"TLR2/4-mediated NF-κB pathway combined with the histone modification regulates β-defensins and interleukins expression by sodium phenyl butyrate in porcine intestinal epithelial cells.","authors":"Dou, Xiujing; Han, Junlan; Ma, Qiuyuan; Cheng, Baojing; Shan, Anshan; Gao, Nan; Yang, Yu","year":2018,"journal":"Food & nutrition research, 62","doi":"10.29219/fnr.v62.1493","pmid":"30574051","tags":["defensins","innate-immunity"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Sodium phenylbutyrate (PBA) boosted the production of beta-defensins (pBD-1, pBD-3) and other host defense peptides in porcine intestinal cells through two independent mechanisms: TLR2/TLR4-mediated activation of the NF-κB inflammatory pathway, and histone modification (HDAC inhibition and histone H3 phosphorylation). Critically, PBA increased defensin production without triggering an excessive inflammatory response.\n\nThe study also identified that p38-MAPK and EGFR signaling pathways are involved in regulating this defensin induction. This dual mechanism — immune receptor activation plus epigenetic modification — suggests that dietary compounds could be used to boost the body's natural antimicrobial peptide defenses in the gut.","whyItMatters":"Instead of giving antibiotics to kill bacteria, this research explores boosting the body's own antimicrobial peptides through dietary means. If compounds like PBA can safely increase defensin production in gut cells without causing harmful inflammation, it could provide a new strategy for fighting intestinal infections — particularly important in agriculture where antibiotic overuse drives resistance, and potentially applicable to human gut health.","specificNumbers":"3 HDPs upregulated (pEP2C, pBD-1, pBD-3) · 2 cytokines upregulated (IL-8, IL-18) · TLR2 + TLR4 pathway · NF-κB activation · HDAC inhibition · histone H3 S10 phosphorylation","methodology":"In vitro study using porcine intestinal epithelial cells (IPEC-J2) treated with sodium phenylbutyrate (PBA). Measured host defense peptide and cytokine expression, TLR2/TLR4 involvement, NF-κB pathway activation (p65 phosphorylation, IκBα dynamics), histone modification (HDAC inhibition, H3 S10 phosphorylation), and MAPK/EGFR signaling pathway roles.","limitations":"Cell culture study using a porcine intestinal cell line — results may not translate directly to intact gut tissue or human intestinal cells. PBA is used as a tool compound and may not represent a practical dietary supplement. The study examined signaling pathways in isolation and may not capture the full complexity of gut immune regulation in a living organism."},{"rthcId":"RPEP-03653","title":"Lactoferrin and Peptide-derivatives: Antimicrobial Agents with Potential Use in Nonspecific Immunity Modulation.","authors":"Drago-Serrano, Maria Elisa; Campos-Rodriguez, Rafael; Carrero, Julio Cesar; de la Garza, Mireya","year":2018,"journal":"Current pharmaceutical design, 24(10), 1067-1078","doi":"10.2174/1381612824666180327155929","pmid":"29589540","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03654","title":"Counteraction of perforated cecum lesions in rats: Effects of pentadecapeptide BPC 157, L-NAME and L-arginine.","authors":"Drmic, Domagoj; Samara, Mariam; Vidovic, Tinka; Malekinusic, Dominik; Antunovic, Marko; Vrdoljak, Borna; Ruzman, Jelena; Milkovic Perisa, Marija; Horvat Pavlov, Katarina; Jeyakumar, Jerusha; Seiwerth, Sven; Sikiric, Predrag","year":2018,"journal":"World journal of gastroenterology, 24(48), 5462-5476","doi":"10.3748/wjg.v24.i48.5462","pmid":"30622376","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03655","title":"Stereotactic body radiation therapy and thymosin alpha-1-induced anti-tumor effects in heavily pretreated, metastatic esophageal squamous cell carcinoma patients.","authors":"Du, Dexi; Song, Tao; Dai, Hui; Jing, Zhao; Chen, Peng; Wu, Shixiu","year":2018,"journal":"Oncoimmunology, 7(8), e1450128","doi":"10.1080/2162402X.2018.1450128","pmid":"30221039","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03656","title":"CGRP Antibodies as Prophylaxis in Migraine.","authors":"Edvinsson, Lars","year":2018,"journal":"Cell, 175(7), 1719","doi":"10.1016/j.cell.2018.11.049","pmid":"30550780","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03657","title":"CGRP as the target of new migraine therapies - successful translation from bench to clinic.","authors":"Edvinsson, Lars; Haanes, Kristian Agmund; Warfvinge, Karin; Krause, Diana N","year":2018,"journal":"Nature reviews. Neurology, 14(6), 338-350","doi":"10.1038/s41582-018-0003-1","pmid":"29691490","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03658","title":"The CGRP Pathway in Migraine as a Viable Target for Therapies.","authors":"Edvinsson, Lars","year":2018,"journal":"Headache, 58 Suppl 1, 33-47","doi":"10.1111/head.13305","pmid":"29697153","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03659","title":"A liquid chromatography high-resolution mass spectrometry in vitro assay to assess metabolism at the injection site of subcutaneously administered therapeutic peptides.","authors":"Esposito, Simone; de Leonibus, Maria Lucia; Ingenito, Raffaele; Bianchi, Elisabetta; Orsatti, Laura; Monteagudo, Edith","year":2018,"journal":"Journal of pharmaceutical and biomedical analysis, 159, 449-458","doi":"10.1016/j.jpba.2018.07.009","pmid":"30041153","tags":["peptide-pharmacology","drug-delivery","subcutaneous-injection"],"studyType":"Method Development / Validation Study","evidenceStrength":"Moderate","keyFinding":"Researchers developed and validated a lab assay (SCiMetPep) that predicts how quickly peptide drugs break down at the subcutaneous injection site — a major factor in how much drug actually reaches the bloodstream. Using tissue from humans, rats, and minipigs, the assay measured degradation rates and identified the specific enzymatic breakdown products for insulin, lixisenatide, exenatide, liraglutide, and semaglutide.\n\nThe in vitro results matched published in vivo data well. When applied to a series of structurally related peptides, injection-site metabolic stability correlated with bioavailability — confirming that what happens to a peptide right at the injection site is a major determinant of how much drug your body actually absorbs. The assay can identify which parts of a peptide are vulnerable to breakdown, guiding chemists to design more stable versions.","whyItMatters":"When you inject a peptide drug under your skin, enzymes in the subcutaneous tissue start breaking it down immediately — before it even reaches your bloodstream. This is why semaglutide (highly stable) works as a once-weekly injection while some other peptides require daily or multiple daily doses. Having a lab test that predicts this breakdown early in drug development means researchers can identify stability problems and engineer solutions before expensive animal and human testing begins.","specificNumbers":"Validated with 5 known peptides (insulin, lixisenatide, exenatide, liraglutide, semaglutide) · human, rat, and minipig SC tissue · half-life + metabolite identification · good correlation between SC stability and bioavailability","methodology":"The researchers developed the SCiMetPep assay using subcutaneous tissue homogenate supernatant from three species: human, Sprague-Dawley rat, and Göttingen minipig. Peptides were incubated with the tissue extracts and analyzed by liquid chromatography-high resolution mass spectrometry. The method measures both the degradation half-life of the parent peptide and identifies specific metabolites from enzymatic proteolysis. Validation was performed by comparing in vitro results to published in vivo pharmacokinetic data for five well-characterized peptide drugs.","limitations":"The assay uses tissue homogenates rather than intact tissue, which may not fully replicate the complexity of in vivo subcutaneous absorption including blood flow, lymphatic drainage, and tissue architecture. The validation was limited to five known peptides, though the correlation with in vivo data was good. Species differences in enzyme activity mean results from one species may not perfectly predict another. The assay predicts metabolic stability but not other factors affecting bioavailability like aggregation or tissue binding."},{"rthcId":"RPEP-03660","title":"Inducers of salmon innate immunity: An in vitro and in vivo approach.","authors":"Estévez, Rosana A; Mostazo, Miriam G Contreras; Rodriguez, Eduardo; Espinoza, Juan Carlos; Kuznar, Juan; Jónsson, Zophonías O; Guðmundsson, Guðmundur H; Maier, Valerie H","year":2018,"journal":"Fish & shellfish immunology, 72, 247-258","doi":"10.1016/j.fsi.2017.10.058","pmid":"29108970","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03661","title":"Effects of metformin on cell growth and AMPK activity in pituitary adenoma cell cultures, focusing on the interaction with adenylyl cyclase activating signals.","authors":"Faggi, Lara; Giustina, Andrea; Tulipano, Giovanni","year":2018,"journal":"Molecular and cellular endocrinology, 470, 60-74","doi":"10.1016/j.mce.2017.09.030","pmid":"28962892","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Metformin inhibited rat pituitary tumor cell growth through AMPK activation and suppression of the mTOR-p70S6 kinase pathway. Crucially, metformin maintained its ability to activate AMPK and inhibit cell growth even in cells treated with forskolin (an adenylyl cyclase activator) and in cells overexpressing the GHRH receptor stimulated with GHRH. This demonstrates that adenylyl cyclase over-activation — a hallmark of some pituitary tumors — does not prevent metformin from working, contradicting concerns that hyperactive cAMP signaling might negate AMPK-based therapies.","whyItMatters":"Growth hormone-secreting pituitary adenomas cause acromegaly, a serious condition with cardiovascular and metabolic complications. Current treatments include surgery and somatostatin analog drugs, but many patients don't respond adequately. Metformin is already widely used, safe, and inexpensive. Showing that it can suppress pituitary tumor growth — even when the GHRH peptide signaling pathway is hyperactive — supports investigating metformin as an adjunctive therapy for these tumors.","specificNumbers":"","methodology":"Researchers used rat pituitary adenoma cell cultures and tested metformin's effects on cell growth, AMPK activation, and downstream signaling pathways (mTOR-p70S6K, ERK). They used MTT assays for cell viability, Western blotting for protein signaling, and tested interactions with forskolin (adenylyl cyclase activator) and GHRH in cells transfected to overexpress the GHRH receptor. Energetic stress conditions were also examined.","limitations":"This study used rat pituitary adenoma cell lines in vitro, not human tumors. The abstract notes that some human pituitary tumors don't respond to AMPK-activating compounds, suggesting species-specific or tumor-specific differences. No in vivo tumor models or clinical data were included. The specific metformin concentrations achieving these effects may not be achievable in the pituitary in humans at standard oral doses."},{"rthcId":"RPEP-03662","title":"Neuropeptides SP and CGRP Underlie the Electrical Properties of Acupoints.","authors":"Fan, Yu; Kim, Do-Hee; Ryu, Yeonhee; Chang, Suchan; Lee, Bong Hyo; Yang, Chae Ha; Kim, Hee Young","year":2018,"journal":"Frontiers in neuroscience, 12, 907","doi":"10.3389/fnins.2018.00907","pmid":"30618546","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03663","title":"MicroRNA-31-3p Is Involved in Substance P (SP)-Associated Inflammation in Human Colonic Epithelial Cells and Experimental Colitis.","authors":"Fang, Kai; Law, Ivy Ka Man; Padua, David; Sideri, Aristea; Huang, Vanessa; Kevil, Christopher G; Iliopoulos, Dimitrios; Pothoulakis, Charalabos","year":2018,"journal":"The American journal of pathology, 188(3), 586-599","doi":"10.1016/j.ajpath.2017.10.023","pmid":"29253460","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03664","title":"Neuroendocrine response to GABA-B receptor agonism in alcohol-dependent individuals: Results from a combined outpatient and human laboratory experiment.","authors":"Farokhnia, Mehdi; Sheskier, Mikela B; Lee, Mary R; Le, April N; Singley, Erick; Bouhlal, Sofia; Ton, Timmy; Zhao, Zhen; Leggio, Lorenzo","year":2018,"journal":"Neuropharmacology, 137, 230-239","doi":"10.1016/j.neuropharm.2018.04.011","pmid":"29665351","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 34 alcohol-dependent individuals receiving baclofen 30 mg/day vs. placebo for one week in a double-blind crossover:\n\nOutpatient phase (1 week of treatment):\n- Acyl-ghrelin significantly increased (P=0.01)\n- Leptin significantly increased (P=0.01)\n- Amylin significantly increased (P=0.004)\n- GLP-1 significantly increased (P=0.02)\n\nLaboratory experiment (alcohol cue-reactivity + self-administration):\n- Significant drug × time-point interactions for amylin (P=0.001) and insulin (P=0.03)\n- Trend-level interactions for GLP-1 (P=0.06) and ACTH (P=0.10)\n- No significant effect on alcohol drinking behavior (P≥0.05)\n\nProlactin, TSH, growth hormone, cortisol, and ACTH were also measured but showed less consistent changes.","whyItMatters":"Understanding how the brain's GABA system controls metabolic peptide hormones has implications for both addiction and obesity treatment. The finding that GABA-B activation simultaneously raises ghrelin (appetite-promoting), GLP-1, amylin, and leptin (appetite-suppressing hormones) reveals a complex neuroendocrine response that may explain why some alcoholism treatments affect eating behavior. These shared pathways between alcohol and food reward could inform the development of drugs that treat both conditions simultaneously.","specificNumbers":"","methodology":"This was a randomized, double-blind, placebo-controlled study. Thirty-four alcohol-dependent individuals received baclofen 30 mg/day or placebo for one week in a naturalistic outpatient setting. They then completed a controlled laboratory experiment including alcohol cue-reactivity, fixed-dose alcohol priming, and self-administration procedures. Blood samples were collected at multiple time points and analyzed for 10 neuroendocrine markers: ghrelin, leptin, amylin, GLP-1, insulin, prolactin, TSH, growth hormone, cortisol, and ACTH.","limitations":"The sample size (34) is modest. Baclofen dose (30 mg/day) is on the lower end of doses used in clinical practice, and higher doses might produce different neuroendocrine effects. The one-week treatment period is short. The negative drinking outcome means baclofen's effects on peptide hormones did not translate into reduced alcohol consumption in this study. The simultaneous increase of both appetite-promoting (ghrelin) and appetite-suppressing (GLP-1, amylin, leptin) hormones is paradoxical and difficult to interpret. Causation versus correlation for the peptide changes cannot be established."},{"rthcId":"RPEP-03665","title":"Pharmacological manipulation of the ghrelin system and alcohol hangover symptoms in heavy drinking individuals: Is there a link?","authors":"Farokhnia, Mehdi; Lee, Mary R; Farinelli, Lisa A; Ramchandani, Vijay A; Akhlaghi, Fatemeh; Leggio, Lorenzo","year":2018,"journal":"Pharmacology, biochemistry, and behavior, 172, 39-49","doi":"10.1016/j.pbb.2018.07.004","pmid":"30030128","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03666","title":"Two novel dual GLP-1/GIP receptor agonists are neuroprotective in the MPTP mouse model of Parkinson's disease.","authors":"Feng, Peng; Zhang, Xiangjian; Li, Dongfang; Ji, Chenhui; Yuan, Ziyue; Wang, Ruifang; Xue, Guofang; Li, Guanglai; Hölscher, Christian","year":2018,"journal":"Neuropharmacology, 133, 385-394","doi":"10.1016/j.neuropharm.2018.02.012","pmid":"29462693","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03667","title":"Targeting dysfunctional beta-cell signaling for the potential treatment of type 1 diabetes mellitus.","authors":"Fenske, Rachel J; Kimple, Michelle E","year":2018,"journal":"Experimental biology and medicine (Maywood, N.J.), 243(6), 586-591","doi":"10.1177/1535370218761662","pmid":"29504478","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03668","title":"Evidence Supporting a Role for Constitutive Ghrelin Receptor Signaling in Fasting-Induced Hyperphagia in Male Mice.","authors":"Fernandez, Gimena; Cabral, Agustina; Andreoli, María F; Labarthe, Alexandra; M'Kadmi, Céline; Ramos, Jorge G; Marie, Jacky; Fehrentz, Jean-Alain; Epelbaum, Jacques; Tolle, Virginie; Perello, Mario","year":2018,"journal":"Endocrinology, 159(2), 1021-1034","doi":"10.1210/en.2017-03101","pmid":"29300858","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03669","title":"Augmenting Prolonged Exposure therapy for PTSD with intranasal oxytocin: A randomized, placebo-controlled pilot trial.","authors":"Flanagan, Julianne C; Sippel, Lauren M; Wahlquist, Amy; Moran-Santa Maria, Megan M; Back, Sudie E","year":2018,"journal":"Journal of psychiatric research, 98, 64-69","doi":"10.1016/j.jpsychires.2017.12.014","pmid":"29294429","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03670","title":"A Clear Difference Emerges in Hormone Patterns Following a Standard Midday Meal in Young Women Who Regularly Eat or Skip Breakfast.","authors":"Forester, Shavawn M; Widaman, Adrianne M; Krishnan, Sridevi; Witbracht, Megan G; Horn, William F; Laugero, Kevin D; Keim, Nancy L","year":2018,"journal":"The Journal of nutrition, 148(5), 685-692","doi":"10.1093/jn/nxy020","pmid":"29897486","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03671","title":"Peptidomimetic growth hormone secretagogue derivatives for positron emission tomography imaging of the ghrelin receptor.","authors":"Fowkes, Milan M; Lalonde, Tyler; Yu, Lihai; Dhanvantari, Savita; Kovacs, Michael S; Luyt, Leonard G","year":2018,"journal":"European journal of medicinal chemistry, 157, 1500-1511","doi":"10.1016/j.ejmech.2018.08.062","pmid":"30282322","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03672","title":"Non-insulin pharmacological therapies for treating type 1 diabetes.","authors":"Frandsen, Christian Seerup; Dejgaard, Thomas Fremming; Madsbad, Sten; Holst, Jens Juul","year":2018,"journal":"Expert opinion on pharmacotherapy, 19(9), 947-960","doi":"10.1080/14656566.2018.1483339","pmid":"29991320","tags":["type-1-diabetes","GLP-1-agonists","pramlintide","adjunct-therapy"],"studyType":"review","evidenceStrength":"review","keyFinding":"This review evaluated all non-insulin drugs studied as add-on therapies for type 1 diabetes, including pramlintide (an amylin analog), GLP-1 receptor agonists, DPP-4 inhibitors, SGLT1/SGLT2 inhibitors, metformin, sulfonylureas, and thiazolidinediones. The bottom line: none provided dramatic improvement. Average HbA1c reductions were a modest 0.2-0.5% (2-6 mmol/mol) across all drug classes.\n\nAt the time of publication, SGLT inhibitors were considered the most promising avenue for further development in type 1 diabetes. The authors identified obese type 1 patients, those with residual beta-cell function, and hypoglycemia-prone patients as subgroups most likely to benefit from adjunct therapy.","whyItMatters":"Many people with type 1 diabetes struggle to achieve blood sugar targets even with intensive insulin therapy. The success of peptide-based drugs like GLP-1 agonists and pramlintide in type 2 diabetes raised hopes they could help type 1 patients too. This review provides a realistic assessment: the benefits exist but are modest, highlighting the fundamental difference between type 1 (autoimmune destruction of insulin-producing cells) and type 2 diabetes.","specificNumbers":"HbA1c reduction: 0.2-0.5% average · 7 drug classes reviewed · Pramlintide, GLP-1 RAs, DPP-4 inhibitors, SGLT1/2 inhibitors, metformin, sulfonylureas, thiazolidinediones","methodology":"Expert review of published clinical trial evidence on non-insulin pharmacological therapies used as adjuncts to insulin in type 1 diabetes, covering efficacy, safety, and adverse event profiles across seven drug classes.","limitations":"Published in 2018, so it predates more recent data on GLP-1 agonists in type 1 diabetes and the FDA's partial approval/rejection of SGLT2 inhibitors for this indication. The modest benefits observed may partly reflect the challenge of studying add-on therapies when baseline insulin therapy already addresses the primary deficiency."},{"rthcId":"RPEP-03673","title":"Anti-LL37 Antibodies Are Present in Psoriatic Arthritis (PsA) Patients: New Biomarkers in PsA.","authors":"Frasca, Loredana; Palazzo, Raffaella; Chimenti, Maria S; Alivernini, Stefano; Tolusso, Barbara; Bui, Laura; Botti, Elisabetta; Giunta, Alessandro; Bianchi, Luca; Petricca, Luca; Auteri, Simone E; Spadaro, Francesca; Fonti, Giulia L; Falchi, Mario; Evangelista, Antonella; Marinari, Barbara; Pietraforte, Immacolata; Spinelli, Francesca R; Colasanti, Tania; Alessandri, Cristiano; Conti, Fabrizio; Gremese, Elisa; Costanzo, Antonio; Valesini, Guido; Perricone, Roberto; Lande, Roberto","year":2018,"journal":"Frontiers in immunology, 9, 1936","doi":"10.3389/fimmu.2018.01936","pmid":"30279686","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03674","title":"Asparaginyl Endopeptidase (Legumain) Supports Human Th1 Induction via Cathepsin L-Mediated Intracellular C3 Activation.","authors":"Freeley, Simon; Cardone, John; Günther, Sira C; West, Erin E; Reinheckel, Thomas; Watts, Colin; Kemper, Claudia; Kolev, Martin V","year":2018,"journal":"Frontiers in immunology, 9, 2449","doi":"10.3389/fimmu.2018.02449","pmid":"30405635","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03675","title":"Conformationally constrained peptides target the allosteric kinase dimer interface and inhibit EGFR activation.","authors":"Fulton, Melody D; Hanold, Laura E; Ruan, Zheng; Patel, Sneha; Beedle, Aaron M; Kannan, Natarajan; Kennedy, Eileen J","year":2018,"journal":"Bioorganic & medicinal chemistry, 26(6), 1167-1173","doi":"10.1016/j.bmc.2017.08.051","pmid":"28911855","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The stapled peptide EHBI2, designed to mimic the H-helix of the EGFR kinase domain, successfully disrupted the asymmetric kinase dimer interface required for EGFR activation. Peptide stapling notably enhanced cell permeation compared to the unconstrained version.\n\nIn cell-based assays, EHBI2 significantly reduced EGFR phosphorylation (the marker of EGFR activation) and phosphorylation of the downstream signaling substrate Akt, confirming disruption of the entire EGFR signaling cascade. This is the first H-helix-based compound targeting the asymmetric dimer interface of the EGFR kinase domain that can successfully inhibit EGFR activation and signaling.","whyItMatters":"Drug resistance is the Achilles' heel of EGFR-targeted cancer therapy — mutations in the active site render current inhibitors ineffective. By targeting a completely different site on EGFR (the allosteric dimer interface), this stapled peptide approach could work even when conventional drugs fail. If developed further, allosteric EGFR inhibitors could provide a new treatment option for patients with resistant lung cancer, head and neck cancer, and other EGFR-driven malignancies.","specificNumbers":"","methodology":"A library of constrained peptides was designed to mimic the H-helix of the EGFR kinase domain, with interface side chains optimized through molecular modeling. Peptides were constrained using hydrocarbon stapling to reinforce alpha-helical conformation. Cell permeation was assessed by fluorescence microscopy. EGFR inhibition was measured in tumor cell lines by monitoring EGFR phosphorylation and Akt phosphorylation using cell-based assays.","limitations":"All experiments were performed in cell-based assays, with no in vivo animal tumor model testing. The specific cancer cell lines used and the magnitude of EGFR inhibition were not quantified in the abstract. Pharmacokinetic properties (stability in blood, half-life) of the stapled peptide are unknown. Manufacturing scalability was not addressed. The study did not compare EHBI2's efficacy to existing EGFR inhibitors or test it against resistance mutations."},{"rthcId":"RPEP-03676","title":"Pramlintide but Not Liraglutide Suppresses Meal-Stimulated Glucagon Responses in Type 1 Diabetes.","authors":"Galderisi, Alfonso; Sherr, Jennifer; VanName, Michelle; Carria, Lori; Zgorski, Melinda; Tichy, Eileen; Weyman, Kate; Cengiz, Eda; Weinzimer, Stuart; Tamborlane, William","year":2018,"journal":"The Journal of clinical endocrinology and metabolism, 103(3), 1088-1094","doi":"10.1210/jc.2017-02265","pmid":"29211871","tags":[],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"Pramlintide (an amylin analog peptide) significantly suppressed meal-stimulated glucagon responses in type 1 diabetes patients after 3–4 weeks of treatment. The glucagon area under the curve dropped by 63% (1,988 to 737 pg/mL/min, p<0.001), and the post-meal glucose rise dropped dramatically (11,963 to 2,493 mg/dL/min, p<0.01).\n\nIn contrast, liraglutide (a GLP-1 receptor agonist) had no effect on either glucagon or glucose responses during mixed-meal testing in type 1 diabetes — a striking failure for a drug that effectively suppresses glucagon in type 2 diabetes.","whyItMatters":"Post-meal blood sugar spikes are one of the biggest challenges in type 1 diabetes management, and excessive glucagon release is a key driver. This head-to-head comparison reveals that pramlintide — a synthetic version of the pancreatic peptide amylin — can suppress this glucagon surge, while liraglutide cannot. This matters because it clarifies which peptide drug actually addresses a fundamental problem in T1D management.","specificNumbers":"Pramlintide group: n=8, age 20±3, HbA1c 6.9% · Liraglutide group: n=10, age 22±3, HbA1c 7.6% · Glucagon AUC: -63% with pramlintide (p<0.001) · Glucose AUC: -79% with pramlintide (p<0.01) · Liraglutide: no significant change","methodology":"Two parallel clinical studies in young adults with type 1 diabetes. Participants underwent mixed-meal tolerance tests (MMTTs) without premeal bolus insulin before and after 3–4 weeks of treatment with either pramlintide (n=8) or liraglutide (n=10). Plasma glucagon and glucose responses were measured over 120 minutes post-meal.","limitations":"Very small sample sizes (8 and 10 patients). The two groups were not randomized against each other — they were parallel studies, making direct comparison less rigorous. No placebo control within either group. Short treatment duration (3–4 weeks). The MMTT was performed without premeal insulin, which doesn't reflect real-world diabetes management."},{"rthcId":"RPEP-03677","title":"Potential and Limitations of Atrial Natriuretic Peptide as Biomarker in Pediatric Heart Failure-A Comparative Review.","authors":"Gangnus, Tanja; Burckhardt, Bjoern B","year":2018,"journal":"Frontiers in pediatrics, 6, 420","doi":"10.3389/fped.2018.00420","pmid":"30761275","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03678","title":"Anchor peptide captures, targets, and loads exosomes of diverse origins for diagnostics and therapy.","authors":"Gao, Xianjun; Ran, Ning; Dong, Xue; Zuo, Bingfeng; Yang, Rong; Zhou, Qibing; Moulton, Hong M; Seow, Yiqi; Yin, HaiFang","year":2018,"journal":"Science translational medicine, 10(444)","doi":"10.1126/scitranslmed.aat0195","pmid":"29875202","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03679","title":"Identification and Pharmacological Profile of an Indane Based Series of Ghrelin Receptor Full Agonists.","authors":"Gardelli, Cristina; Wada, Hiroki; Ray, Asim; Caffrey, Moya; Llinas, Antonio; Shamovsky, Igor; Tholander, Joakim; Larsson, Joakim; Sivars, Ulf; Hultin, Leif; Andersson, Ulf; Sanganee, Hitesh J; Stenvall, Kristina; Leidvik, Brith; Gedda, Karin; Jinton, Lisa; Rydén Landergren, Marie; Karabelas, Kostas","year":2018,"journal":"Journal of medicinal chemistry, 61(14), 5974-5987","doi":"10.1021/acs.jmedchem.8b00322","pmid":"29909635","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03680","title":"Effects of Teriparatide Compared with Risedronate on the Risk of Fractures in Subgroups of Postmenopausal Women with Severe Osteoporosis: The VERO Trial.","authors":"Geusens, Piet; Marin, Fernando; Kendler, David L; Russo, Luis A; Zerbini, Cristiano Af; Minisola, Salvatore; Body, Jean Jacques; Lespessailles, Eric; Greenspan, Susan L; Bagur, Alicia; Stepan, Jan J; Lakatos, Péter; Casado, Enrique; Moericke, Rüdiger; López-Romero, Pedro; Fahrleitner-Pammer, Astrid","year":2018,"journal":"Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 33(5), 783-794","doi":"10.1002/jbmr.3384","pmid":"29329484","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03681","title":"Evaluation of serum level of substance P and tissue distribution of NK-1 receptor in endometrial cancer.","authors":"Gharaee, Naghmeh; Pourali, Leila; Jafarian, Amir Hossein; Hashemy, Seyed Isaac","year":2018,"journal":"Molecular biology reports, 45(6), 2257-2262","doi":"10.1007/s11033-018-4387-1","pmid":"30225581","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03682","title":"Type 2 diabetes and cardiovascular prevention: the dogmas disputed.","authors":"Giugliano, Dario; Maiorino, Maria Ida; Bellastella, Giuseppe; Esposito, Katherine","year":2018,"journal":"Endocrine, 60(2), 224-228","doi":"10.1007/s12020-017-1418-y","pmid":"28895030","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03683","title":"Episodic Ethanol Exposure in Adolescent Rats Causes Residual Alterations in Endogenous Opioid Peptides.","authors":"Granholm, Linnea; Segerström, Lova; Nylander, Ingrid","year":2018,"journal":"Frontiers in psychiatry, 9, 425","doi":"10.3389/fpsyt.2018.00425","pmid":"30250435","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03684","title":"An explorative study towards the chemical synthesis of the immunoglobulin G1 Fc CH3 domain.","authors":"Grassi, Luigi; Roschger, Cornelia; Stanojlović, Vesna; Cabrele, Chiara","year":2018,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 24(12), e3126","doi":"10.1002/psc.3126","pmid":"30346065","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03685","title":"Protective Role of Rabbit Nucleotide-Binding Oligomerization Domain-2 (NOD2)-Mediated Signaling Pathway in Resistance to Enterohemorrhagic Escherichia coli Infection.","authors":"Guo, Mengjiao; Li, Rong; Xiao, Qianqian; Fan, Xiuxiu; Li, Ning; Shang, Yingli; Wei, Liangmeng; Chai, Tongjie","year":2018,"journal":"Frontiers in cellular and infection microbiology, 8, 220","doi":"10.3389/fcimb.2018.00220","pmid":"29998088","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03686","title":"Oxidative Stress Contributes to Fracture/Cast-Induced Inflammation and Pain in a Rat Model of Complex Regional Pain Syndrome.","authors":"Guo, Tian-Zhi; Wei, Tzuping; Huang, Ting-Ting; Kingery, Wade S; Clark, John David","year":2018,"journal":"The journal of pain, 19(10), 1147-1156","doi":"10.1016/j.jpain.2018.04.006","pmid":"29715519","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03687","title":"Chronic Intranasal Oxytocin has Dose-dependent Effects on Central Oxytocin and Vasopressin Systems in Prairie Voles (Microtus ochrogaster).","authors":"Guoynes, C D; Simmons, T C; Downing, G M; Jacob, S; Solomon, M; Bales, K L","year":2018,"journal":"Neuroscience, 369, 292-302","doi":"10.1016/j.neuroscience.2017.11.037","pmid":"29183825","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03688","title":"Recombinant human follicle stimulating hormone purification by a short peptide affinity chromatography.","authors":"Gurevich Messina, Juan M; Giudicessi, Silvana L; Martínez Ceron, María C; Urtasun, Nicolás; Forno, Guillermina; Mauro, Laura; Cascone, Osvaldo; Camperi, Silvia A","year":2018,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 24(11), e3128","doi":"10.1002/psc.3128","pmid":"30288867","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03689","title":"Inhibition of Inflammatory Changes in Human Myometrial Cells by Cell Penetrating Peptide and Small Molecule Inhibitors of NFκB.","authors":"Gurney, Leo R I; Taggart, Julie; Tong, Wing-Chiu; Jones, Arwyn T; Robson, Stephen C; Taggart, Michael J","year":2018,"journal":"Frontiers in immunology, 9, 2966","doi":"10.3389/fimmu.2018.02966","pmid":"30619324","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03690","title":"Low-dose calcipotriol can elicit wound closure, anti-microbial, and anti-neoplastic effects in epidermolysis bullosa keratinocytes.","authors":"Guttmann-Gruber, Christina; Tockner, Birgit; Scharler, Cornelia; Hüttner, Clemens; Common, John E; Tay, Angeline S L; Denil, Simon L I J; Klausegger, Alfred; Trost, Andrea; Breitenbach, Jenny; Schnitzhofer, Peter; Hofbauer, Peter; Wolkersdorfer, Martin; Diem, Anja; Laimer, Martin; Strunk, Dirk; Bauer, Johann W; Reichelt, Julia; Lang, Roland; Piñón Hofbauer, Josefina","year":2018,"journal":"Scientific reports, 8(1), 13430","doi":"10.1038/s41598-018-31823-6","pmid":"30194425","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03691","title":"Recent improvements in sports drug testing concerning the initial testing for peptidic drugs (< 2 kDa) - sample preparation, mass spectrometric detection, and data review.","authors":"Görgens, Christian; Guddat, Sven; Thomas, Andreas; Thevis, Mario","year":2018,"journal":"Drug testing and analysis, 10(11-12), 1755-1760","doi":"10.1002/dta.2503","pmid":"30239151","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The new assay achieved detection limits of 50-200 pg/mL for banned peptidic drugs under 2 kilodaltons, covering:\n\n• Gonadotropin releasing hormone (GnRH) and its analogs\n• Growth hormone secretagogues (GHS)\n• Growth hormone releasing peptides (GHRPs)\n• Desmopressin (a vasopressin analog)\n\nThe 'dilute-and-inject' strategy eliminated complex sample preparation while maintaining high sensitivity and specificity. The method combined two-dimensional liquid chromatography, DMSO-assisted electrospray ionization, and high-resolution mass spectrometric detection. A tailored reporter template facilitated rapid data review, enabling high-throughput screening.","whyItMatters":"Peptide doping is one of the hardest forms of cheating to detect in sports because peptide drugs are present in very small amounts and break down quickly in the body. This method makes routine peptide screening faster and more practical, closing a gap that some athletes have exploited. As more performance-enhancing peptides enter the black market, anti-doping labs need efficient methods to keep up — and this 'dilute-and-inject' approach dramatically simplifies the process.","specificNumbers":"","methodology":"The researchers developed and validated a liquid chromatography-mass spectrometry (LC-MS) assay for detecting small peptidic drugs in biological samples. The approach used a 'dilute-and-inject' sample preparation strategy, two-dimensional liquid chromatography for separation, DMSO-enhanced electrospray ionization for improved sensitivity, and high-resolution mass spectrometry for detection. A custom reporter template was created to streamline data review for routine screening.","limitations":"The abstract describes the analytical method development but does not report validation data from real athlete samples or false positive/negative rates. Detection limits of 50-200 pg/mL, while impressive, may still miss some peptides administered at very low doses or with short detection windows. The method covers specific classes of peptides under 2 kDa and may not detect newer designer peptides outside these categories. Real-world matrix effects from diverse athlete urine samples could affect performance."},{"rthcId":"RPEP-03692","title":"Postprandial gut hormone responses to Hass avocado meals and their association with visual analog scores in overweight adults: A randomized 3 × 3 crossover trial.","authors":"Haddad, Ella; Wien, Michelle; Oda, Keiji; Sabaté, Joan","year":2018,"journal":"Eating behaviors, 31, 35-40","doi":"10.1016/j.eatbeh.2018.08.001","pmid":"30096700","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In a crossover trial comparing three lunch meals (control, avocado-inclusive, avocado-added):\n\n- The avocado-added meal decreased the 3-hour GLP-1 AUC compared to control (P = 0.03)\n- PYY3-36 and GIP showed negative associations with hunger, desire to eat, and 'how much could you eat' (all P < 0.001)\n- PYY3-36 and GIP showed positive associations with fullness, satisfaction, and composite appetite score (all P < 0.001)\n- GLP-1 was negatively associated with hunger and positively associated with satisfaction and composite score (all P < 0.05)\n- Ghrelin (the hunger hormone) results were not highlighted as significant","whyItMatters":"Understanding how different foods affect satiety peptide release is key to designing diets that naturally promote fullness and reduce overeating. This study shows that the relationship between food composition and gut peptide responses is complex — adding a healthy fat like avocado doesn't necessarily increase appetite-suppressing peptides like GLP-1.","specificNumbers":"","methodology":"Randomized 3×3 crossover design with 26 healthy overweight adults. Three test meals separated by one week: avocado-free control, isocaloric avocado-inclusive, and higher-calorie avocado-added. Blood samples collected at multiple time points measured ghrelin, PYY3-36, GIP, and GLP-1. Appetite sensations assessed via visual analog scales at matching time points. Mixed models and regression analysis evaluated differences and associations.","limitations":"Small sample (26 participants) limits statistical power. Single-meal acute testing may not reflect chronic dietary patterns. The avocado-added meal was higher in calories than the control, confounding the comparison. Only overweight adults were studied; normal-weight or obese individuals may respond differently. The clinical significance of the GLP-1 decrease with avocado is unclear."},{"rthcId":"RPEP-03693","title":"Cancer vaccine formulation dictates synergy with CTLA-4 and PD-L1 checkpoint blockade therapy.","authors":"Hailemichael, Yared; Woods, Amber; Fu, Tihui; He, Qiuming; Nielsen, Michael C; Hasan, Farah; Roszik, Jason; Xiao, Zhilan; Vianden, Christina; Khong, Hiep; Singh, Manisha; Sharma, Meenu; Faak, Faisal; Moore, Derek; Dai, Zhimin; Anthony, Scott M; Schluns, Kimberly S; Sharma, Padmanee; Engelhard, Victor H; Overwijk, Willem W","year":2018,"journal":"The Journal of clinical investigation, 128(4), 1338-1354","doi":"10.1172/JCI93303","pmid":"29480817","tags":["cancer-immunotherapy","peptide-vaccines"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"In a mouse melanoma model, gp100 peptide vaccine formulated in incomplete Freund's adjuvant (IFA) induced antigen-specific T cells that forcibly redirected other anti-CTLA-4-induced T cells away from the tumor to the vaccination site. This inflammatory trap was driven by a vicious cycle: T cells at the injection site recruited inflammatory monocytes via IFN-γ, which in turn attracted more T cells through CXCR3, ICAM-1, and CCL2 signaling — all dependent on the persistent IFA depot.\n\nIn contrast, non-persistent vaccine formulations — dendritic cell vaccines, viral vector vaccines, or water-soluble peptide formulations — synergized powerfully with both anti-CTLA-4 and anti-PD-L1 checkpoint blockade. These combinations achieved complete tumor regression, even in tumors that were primarily resistant to dual checkpoint blockade alone.","whyItMatters":"This study solved a critical mystery in cancer immunotherapy: why adding a peptide vaccine to ipilimumab failed in the pivotal clinical trial that led to FDA approval. By revealing that the adjuvant — not the peptide itself — was the problem, it rescued the entire concept of peptide cancer vaccines and showed a clear path forward. The finding that reformulated peptide vaccines could overcome even primary resistance to dual checkpoint blockade suggests enormous untapped potential for combination immunotherapy.","specificNumbers":"Complete tumor regression with non-persistent formulations + dual checkpoint blockade; IFA formulation eliminated anti-CTLA-4 benefit","methodology":"The researchers used a mouse melanoma model to test gp100 peptide vaccines in multiple formulations combined with anti-CTLA-4 and anti-PD-L1 antibodies. They tracked T cell movement between the tumor and vaccination site, used molecular tools to identify the signaling pathways (IFN-γ, CXCR3, ICAM-1, CCL2) that created the T cell trap, and compared persistent (IFA) versus non-persistent (dendritic cells, viral vectors, water-soluble) vaccine formulations for their ability to synergize with checkpoint immunotherapy.","limitations":"All experiments were conducted in mouse melanoma models, which don't fully recapitulate human cancer immunology. The specific formulations that worked in mice (dendritic cells, viral vectors, water-soluble peptides) haven't been validated in human clinical trials in combination with modern checkpoint blockade. The study focused on a single tumor antigen (gp100) and one tumor type."},{"rthcId":"RPEP-03694","title":"Pharmacokinetics and Clinical Implications of Semaglutide: A New Glucagon-Like Peptide (GLP)-1 Receptor Agonist.","authors":"Hall, Sylvie; Isaacs, Diana; Clements, Jennifer N","year":2018,"journal":"Clinical pharmacokinetics, 57(12), 1529-1538","doi":"10.1007/s40262-018-0668-z","pmid":"29915923","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03695","title":"From the Anti-Nociceptive Substance P Metabolite Substance P (1-7) to Small Peptidomimetics.","authors":"Hallberg, Mathias; Sandstrom, Anja","year":2018,"journal":"Current protein & peptide science, 19(11), 1038-1048","doi":"10.2174/1389203719666180508122019","pmid":"29745331","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03696","title":"Potent effect of KISS1-54 DNA vaccine compared with KISS1-10 DNA vaccine in inhibiting the fertility of female rats.","authors":"Han, Yanguo; Peng, Xiaoli; Li, Kai; Jiang, Xunping; Liu, Guiqiong; Yang, Liguo; Liang, Caiyou; Zhao, Yuhetian; Huang, Yongjie; E, Guangxin; Zhao, Yongju; Huang, Yongfu","year":2018,"journal":"Vaccine, 36(45), 6631-6639","doi":"10.1016/j.vaccine.2018.09.053","pmid":"30274867","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03697","title":"Glycemic Efficacy, Weight Effects, and Safety of Once-Weekly Glucagon-Like Peptide-1 Receptor Agonists.","authors":"Handelsman, Yehuda; Wyne, Kathleen; Cannon, Anthony; Shannon, Michael; Schneider, Doron","year":2018,"journal":"Journal of managed care & specialty pharmacy, 24(9-a Suppl), S14-S29","doi":"10.18553/jmcp.2018.24.9-a.s14","pmid":"30156445","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Once-weekly GLP-1 receptor agonists effectively lower HbA1c and body weight in type 2 diabetes with a low risk of hypoglycemia. Semaglutide showed the greatest reductions in both HbA1c and body weight in head-to-head comparisons with exenatide ER and dulaglutide. Exenatide ER and dulaglutide demonstrated similar or superior efficacy to oral antidiabetic drugs. All once-weekly GLP-1 RAs were effective as both monotherapy and add-on therapy to various background medications including insulin. Gastrointestinal side effects (nausea, vomiting, diarrhea) were the most common adverse events.","whyItMatters":"The shift from daily to weekly injections was a major advance in GLP-1 peptide therapeutics, improving patient convenience and adherence. This review compares the three weekly GLP-1 RAs available at the time and highlights semaglutide's emerging superiority — foreshadowing its rise to become the most widely prescribed drug in this class. Understanding the comparative efficacy of these peptide drugs helps guide clinical decision-making.","specificNumbers":"3 weekly GLP-1 RAs compared (exenatide ER, dulaglutide, semaglutide) · semaglutide superior for A1c and weight vs exenatide ER and dulaglutide · low hypoglycemia rates · GI adverse events most common · effective as monotherapy and combination therapy","methodology":"This is a narrative review and supplement article synthesizing data from clinical trials of once-weekly GLP-1 receptor agonists including exenatide ER, dulaglutide, and semaglutide. It covers monotherapy data, head-to-head comparisons, add-on therapy with various background medications, and safety profiles.","limitations":"This supplement was funded by Novo Nordisk (semaglutide manufacturer), and most authors reported financial relationships with pharmaceutical companies. The review was published before the full scope of semaglutide's clinical program was complete, so longer-term and cardiovascular outcome data were not fully available. Head-to-head trial comparisons have limitations including different baseline patient characteristics."},{"rthcId":"RPEP-03698","title":"Oxytocin Reduces Alcohol Cue-Reactivity in Alcohol-Dependent Rats and Humans.","authors":"Hansson, Anita C; Koopmann, Anne; Uhrig, Stefanie; Bühler, Sina; Domi, Esi; Kiessling, Eva; Ciccocioppo, Roberto; Froemke, Robert C; Grinevich, Valery; Kiefer, Falk; Sommer, Wolfgang H; Vollstädt-Klein, Sabine; Spanagel, Rainer","year":2018,"journal":"Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 43(6), 1235-1246","doi":"10.1038/npp.2017.257","pmid":"29090683","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03699","title":"A review of the design and modification of lactoferricins and their derivatives.","authors":"Hao, Ya; Yang, Na; Teng, Da; Wang, Xiumin; Mao, Ruoyu; Wang, Jianhua","year":2018,"journal":"Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine, 31(3), 331-341","doi":"10.1007/s10534-018-0086-6","pmid":"29455278","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03700","title":"Crystal Structures of Anti-apoptotic BFL-1 and Its Complex with a Covalent Stapled Peptide Inhibitor.","authors":"Harvey, Edward P; Seo, Hyuk-Soo; Guerra, Rachel M; Bird, Gregory H; Dhe-Paganon, Sirano; Walensky, Loren D","year":2018,"journal":"Structure (London, England : 1993), 26(1), 153-160.e4","doi":"10.1016/j.str.2017.11.016","pmid":"29276033","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03701","title":"Binding conformation and determinants of a single-chain peptide antagonist at the relaxin-3 receptor RXFP3.","authors":"Haugaard-Kedström, Linda M; Lee, Han Siean; Jones, Maryon V; Song, Angela; Rathod, Vishaal; Hossain, Mohammed Akhter; Bathgate, Ross A D; Rosengren, K Johan","year":2018,"journal":"The Journal of biological chemistry, 293(41), 15765-15776","doi":"10.1074/jbc.RA118.002611","pmid":"30131342","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03702","title":"A truncated RHAMM protein for discovering novel therapeutic peptides.","authors":"Hauser-Kawaguchi, Alexandra; Tolg, Cornelia; Peart, Teresa; Milne, Mark; Turley, Eva A; Luyt, Leonard G","year":2018,"journal":"Bioorganic & medicinal chemistry, 26(18), 5194-5203","doi":"10.1016/j.bmc.2018.09.018","pmid":"30249497","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03703","title":"Update on the pharmacology of calcitonin/CGRP family of peptides: IUPHAR Review 25.","authors":"Hay, Debbie L; Garelja, Michael L; Poyner, David R; Walker, Christopher S","year":2018,"journal":"British journal of pharmacology, 175(1), 3-17","doi":"10.1111/bph.14075","pmid":"29059473","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03704","title":"Evaluation of Hypothalamic-Pituitary-Adrenal Axis by the GHRP2 Test: Comparison With the Insulin Tolerance Test.","authors":"Hayakawa, Tomoaki; Kitamura, Tetsuhiro; Tamada, Daisuke; Mukai, Kosuke; Hayashi, Reiko; Takahara, Mitsuyoshi; Otsuki, Michio; Shimomura, Iichiro","year":2018,"journal":"Journal of the Endocrine Society, 2(8), 860-869","doi":"10.1210/js.2018-00102","pmid":"30324179","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A strong correlation was found between maximum cortisol levels measured by the GHRP-2 test and the insulin tolerance test (r = 0.777, P < 0.001). In male subjects without functional adenoma (n = 104), the GHRP-2 test achieved high sensitivity (95%) and specificity (85%) for diagnosing adrenocortical insufficiency.\n\nThe results support using the GHRP-2 test as a substitute for the insulin tolerance test when evaluating HPA axis function in male patients free of functional pituitary adenomas. However, the test's performance was affected by sex and the presence of functional adenomas, limiting its applicability in those subgroups.","whyItMatters":"The insulin tolerance test is considered the gold standard for evaluating adrenal function but requires inducing hypoglycemia, which can be dangerous — especially for patients with seizure disorders, heart disease, or severe pituitary insufficiency. The GHRP-2 test stimulates the same adrenal axis through a different, safer mechanism. Validating this peptide-based alternative gives clinicians a safer diagnostic tool for a substantial portion of their patients.","specificNumbers":"","methodology":"This was a retrospective study analyzing clinical and laboratory data from 254 patients admitted for evaluation of hypopituitarism who underwent both the GHRP-2 test and the insulin tolerance test. Researchers compared maximum cortisol responses (Fmax) between the two tests using correlation analysis. Adrenocortical insufficiency was diagnosed using ITT as the reference standard. The suitability of the GHRP-2 test was assessed using receiver operating characteristic (ROC) curve analysis.","limitations":"This was a retrospective study, which is inherently less rigorous than a prospective design. The GHRP-2 test performed less well in female patients and those with functional pituitary adenomas, significantly limiting its universal applicability. The study used the insulin tolerance test as the reference standard, but the ITT itself has imperfect reproducibility. The specific cortisol cutoff values used were not detailed in the abstract."},{"rthcId":"RPEP-03705","title":"Drug delivery using polyhistidine peptide-modified liposomes that target endogenous lysosome.","authors":"Hayashi, Taiki; Shinagawa, Matsumi; Kawano, Tsuyoshi; Iwasaki, Takashi","year":2018,"journal":"Biochemical and biophysical research communications, 501(3), 648-653","doi":"10.1016/j.bbrc.2018.05.037","pmid":"29746864","tags":[],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"A cell-penetrating peptide made of 16 histidine residues (H16) was successfully used to modify liposomes, creating a delivery system that enters cells and naturally targets lysosomes. The H16-modified liposomes (H16-Lipo) were internalized by human fibrosarcoma cells via multiple endocytosis pathways and localized specifically to intracellular lysosomes.\n\nAs proof of concept, the H16-Lipo delivered alpha-galactosidase A (GLA) — a lysosomal enzyme — to the lysosomes of GLA-knockdown cells and improved their proliferation. This demonstrates the system's potential for treating lysosomal storage diseases, where patients lack specific lysosomal enzymes.","whyItMatters":"Lysosomal storage diseases (LSDs) are a group of ~50 rare genetic disorders caused by missing lysosomal enzymes, affecting roughly 1 in 5,000 births. Current enzyme replacement therapies often struggle to get enzymes inside cells and specifically into lysosomes. A peptide-modified liposome that naturally targets lysosomes could dramatically improve drug delivery for these devastating conditions.","specificNumbers":"H16 peptide: 16 histidine residues · Stearyl-H16 inserted into liposome membrane · Delivered alpha-galactosidase A (GLA) · Improved proliferation of GLA-knockdown cells · Human fibrosarcoma cell line","methodology":"Researchers prepared liposomes modified with a stearyl-H16 peptide (the fatty acid anchor inserts into the liposome membrane). They tested cellular uptake in human fibrosarcoma cells, identified the endocytosis pathways involved, tracked intracellular localization, and then loaded the liposomes with GLA enzyme to test functional delivery to lysosomes in GLA-deficient cells.","limitations":"This is an in vitro study using a single cancer cell line (fibrosarcoma), which may not reflect uptake in normal human cells or in vivo conditions. No animal studies were conducted. The abstract doesn't report quantitative uptake efficiency, GLA activity restoration levels, or comparison with existing enzyme replacement delivery methods. Long-term stability and immunogenicity of H16-Lipo were not assessed."},{"rthcId":"RPEP-03706","title":"Sequentially Triggered Nanoparticles with Tumor Penetration and Intelligent Drug Release for Pancreatic Cancer Therapy.","authors":"He, Xi; Chen, Xinli; Liu, Lisha; Zhang, Yu; Lu, Yifei; Zhang, Yujie; Chen, Qinjun; Ruan, Chunhui; Guo, Qin; Li, Chao; Sun, Tao; Jiang, Chen","year":2018,"journal":"Advanced science (Weinheim, Baden-Wurttemberg, Germany), 5(5), 1701070","doi":"10.1002/advs.201701070","pmid":"29876225","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03707","title":"Substance P and dopamine interact to modulate the distribution of delta-opioid receptors on cholinergic interneurons in the striatum.","authors":"Heath, Emily; Chieng, Billy; Christie, Macdonald J; Balleine, Bernard W","year":2018,"journal":"The European journal of neuroscience, 47(10), 1159-1173","doi":"10.1111/ejn.13750","pmid":"29055101","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03708","title":"Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial.","authors":"Hernandez, Adrian F; Green, Jennifer B; Janmohamed, Salim; D'Agostino, Ralph B; Granger, Christopher B; Jones, Nigel P; Leiter, Lawrence A; Rosenberg, Anne E; Sigmon, Kristina N; Somerville, Matthew C; Thorpe, Karl M; McMurray, John J V; Del Prato, Stefano","year":2018,"journal":"Lancet (London, England), 392(10157), 1519-1529","doi":"10.1016/S0140-6736(18)32261-X","pmid":"30291013","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The primary composite outcome of cardiovascular death, myocardial infarction, or stroke occurred in 338 patients (7%) in the albiglutide group at a rate of 4.6 events per 100 person-years, compared to 428 patients (9%) in the placebo group at 5.9 events per 100 person-years. This yielded a hazard ratio of 0.78 (95% CI: 0.68–0.90), demonstrating superiority of albiglutide over placebo (p=0.0006 for superiority, p<0.0001 for non-inferiority).\n\nSafety outcomes were reassuring: acute pancreatitis occurred in 10 albiglutide vs. 7 placebo patients, pancreatic cancer in 6 vs. 5 patients, and medullary thyroid carcinoma in zero patients in both groups. Treatment-related deaths were rare (2 in albiglutide, 3 in placebo).","whyItMatters":"Harmony Outcomes was one of the pivotal cardiovascular outcomes trials that established GLP-1 receptor agonists as not just diabetes medications but cardiovascular protective agents. This trial specifically showed that the cardiovascular benefits extend to albiglutide, broadening the evidence base for the entire GLP-1 class. These results contributed to major guideline changes recommending GLP-1 agonists for diabetic patients with cardiovascular disease, regardless of blood sugar control.","specificNumbers":"","methodology":"This was a double-blind, randomized, placebo-controlled trial (Harmony Outcomes) conducted across 610 sites in 28 countries. Patients aged 40 and older with type 2 diabetes and established cardiovascular disease were randomly assigned 1:1 to receive weekly subcutaneous albiglutide (30–50 mg, titrated based on glycemic response and tolerability) or matched placebo, added to standard care. Treatment assignment was masked via interactive voice/web response system. The primary endpoint was the first occurrence of cardiovascular death, myocardial infarction, or stroke, analyzed by intention-to-treat. A prespecified closed testing procedure first tested non-inferiority (upper 95% CI for HR <1.30), then superiority.","limitations":"The median follow-up of 1.6 years was relatively short for a cardiovascular outcomes trial, so longer-term benefits or risks may not be captured. Albiglutide was subsequently withdrawn from the market for commercial reasons (not safety concerns), limiting the direct clinical applicability of these specific results — though the class-level evidence remains highly relevant. The trial enrolled patients with established cardiovascular disease, so results may not generalize to primary prevention populations. The dose range (30–50 mg) was fixed, and optimal dosing for cardiovascular benefit is unclear."},{"rthcId":"RPEP-03709","title":"Cognitive benefits of angiotensin IV and angiotensin-(1-7): A systematic review of experimental studies.","authors":"Ho, Jean K; Nation, Daniel A","year":2018,"journal":"Neuroscience and biobehavioral reviews, 92, 209-225","doi":"10.1016/j.neubiorev.2018.05.005","pmid":"29733881","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In this systematic review of 32 animal studies, angiotensin IV (Ang IV) improved cognitive performance in 7 of 11 studies in normal animals and 8 of 9 studies in cognitively impaired models. Ang IV and its analogs (including dihexa and Nle1-Ang IV) enhanced spatial working memory, passive avoidance, and object recognition. Angiotensin-(1-7) benefited memory in 2 of 3 studies and showed anti-dementia properties. The peptides were most effective when delivered directly into the brain (intracerebroventricularly) close to the time of learning or memory testing.","whyItMatters":"Dementia and cognitive decline affect tens of millions of people, and effective treatments remain elusive. This systematic review reveals that two peptides from the brain's own renin-angiotensin system can improve memory and learning in animal models — including models of cognitive impairment. The connection between blood pressure peptides and brain function is an underappreciated research area that could yield new treatments for Alzheimer's disease and other dementias.","specificNumbers":"","methodology":"The researchers conducted a systematic review of experimental (non-human) studies, searching databases and identifying 450 articles. Of these, 32 met inclusion criteria. Studies were categorized by peptide type (Ang IV or Ang-(1-7)), cognitive test (passive avoidance, spatial memory, object recognition), and whether animals were normal or cognitively impaired. Results were synthesized narratively.","limitations":"All 32 studies were in animals, primarily rodents, so translation to humans is uncertain. Most studies used intracerebroventricular delivery (directly into the brain), which isn't practical for human treatment. The review could not perform meta-analysis due to heterogeneity in study designs. Sample sizes of individual studies varied. Only acute (single-dose) administration was studied in most cases."},{"rthcId":"RPEP-03710","title":"A platform for discovery of functional cell-penetrating peptides for efficient multi-cargo intracellular delivery.","authors":"Hoffmann, Katrin; Milech, Nadia; Juraja, Suzy M; Cunningham, Paula T; Stone, Shane R; Francis, Richard W; Anastasas, Mark; Hall, Clinton M; Heinrich, Tatjana; Bogdawa, Heique M; Winslow, Scott; Scobie, Marie N; Dewhurst, Robert E; Florez, Laura; Ong, Ferrer; Kerfoot, Maria; Champain, Danie; Adams, Abbie M; Fletcher, Susan; Viola, Helena M; Hool, Livia C; Connor, Theresa; Longville, Brooke A C; Tan, Yew-Foon; Kroeger, Karen; Morath, Volker; Weiss, Gregory A; Skerra, Arne; Hopkins, Richard M; Watt, Paul M","year":2018,"journal":"Scientific reports, 8(1), 12538","doi":"10.1038/s41598-018-30790-2","pmid":"30135446","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03711","title":"In Vitro and In Vivo Characterization of Novel Stable Peptidic Ghrelin Analogs: Beneficial Effects in the Settings of Lipopolysaccharide-Induced Anorexia in Mice.","authors":"Holubová, Martina; Blechová, Miroslava; Kákonová, Anna; Kuneš, Jaroslav; Železná, Blanka; Maletínská, Lenka","year":2018,"journal":"The Journal of pharmacology and experimental therapeutics, 366(3), 422-432","doi":"10.1124/jpet.118.249086","pmid":"29914876","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03712","title":"Chlamydial Plasmid-Encoded Protein pGP3 Inhibits Development of Psoriasis-Like Lesions in Mice.","authors":"Hou, Shuping; Xu, Rong; Zhu, Congzhong; Shan, Shijun; Han, Long; Wang, Huiping","year":2018,"journal":"Medical science monitor : international medical journal of experimental and clinical research, 24, 5159-5167","doi":"10.12659/MSM.910472","pmid":"30043770","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03713","title":"Cell adhesion properties of human defensins.","authors":"Howell, Katie; de Leeuw, Erik","year":2018,"journal":"Biochemical and biophysical research communications, 502(2), 238-242","doi":"10.1016/j.bbrc.2018.05.150","pmid":"29800568","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03714","title":"Antifertility effectiveness of a novel copper-containing intrauterine device material and its influence on the endometrial environment in rats.","authors":"Hu, Shifu; Wang, Yingying; Ke, Dandan; Zhou, Fang; Cheng, Guiping; Xia, Wei; Zhu, Changhong","year":2018,"journal":"Materials science & engineering. C, Materials for biological applications, 89, 444-455","doi":"10.1016/j.msec.2018.04.025","pmid":"29752117","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03715","title":"Substance P as a putative efferent transmitter mediates GABAergic inhibition in mouse taste buds.","authors":"Huang, Anthony Y; Wu, Sandy Y","year":2018,"journal":"British journal of pharmacology, 175(7), 1039-1053","doi":"10.1111/bph.14142","pmid":"29328505","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03716","title":"Differential Effects of Statins on Inflammatory Interleukin-8 and Antimicrobial Peptide Human Β-Defensin 2 Responses in Salmonella-Infected Intestinal Epithelial Cells.","authors":"Huang, Fu-Chen; Huang, Shun-Chen","year":2018,"journal":"International journal of molecular sciences, 19(6)","doi":"10.3390/ijms19061650","pmid":"29865262","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03717","title":"Glucagon-like peptide-1 receptor (GLP-1R) signaling ameliorates dysfunctional immunity in COPD patients.","authors":"Huang, Jingwen; Yi, Huahua; Zhao, Chunliu; Zhang, Yifan; Zhu, Liying; Liu, Bing; He, Ping; Zhou, Min","year":2018,"journal":"International journal of chronic obstructive pulmonary disease, 13, 3191-3202","doi":"10.2147/COPD.S175145","pmid":"30349227","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03718","title":"Coordinated responses to individual tumor antigens by IgG antibody and CD8+ T cells following cancer vaccination.","authors":"Hulett, Tyler W; Jensen, Shawn M; Wilmarth, Phillip A; Reddy, Ashok P; Ballesteros-Merino, Carmen; Afentoulis, Michael E; Dubay, Christopher; David, Larry L; Fox, Bernard A","year":2018,"journal":"Journal for immunotherapy of cancer, 6(1), 27","doi":"10.1186/s40425-018-0331-0","pmid":"29618380","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03719","title":"The role of IL-6 in exercise-induced anorexia in normal-weight boys.","authors":"Hunschede, Sascha; Schwartz, Alexander; Kubant, Ruslan; Thomas, Scott G; Anderson, G Harvey","year":2018,"journal":"Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme, 43(10), 979-987","doi":"10.1139/apnm-2018-0019","pmid":"29590534","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03720","title":"Novel dual GLP-1/GIP receptor agonists show neuroprotective effects in Alzheimer's and Parkinson's disease models.","authors":"Hölscher, Christian","year":2018,"journal":"Neuropharmacology, 136(Pt B), 251-259","doi":"10.1016/j.neuropharm.2018.01.040","pmid":"29402504","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03721","title":"Skin Regeneration with a Scaffold of Predefined Shape and Bioactive Peptide Hydrogels.","authors":"Im, Heejung; Kim, Su Hee; Kim, Soo Hyun; Jung, Youngmee","year":2018,"journal":"Tissue engineering. Part A, 24(19-20), 1518-1530","doi":"10.1089/ten.TEA.2017.0489","pmid":"29756539","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03722","title":"CGRP Monoclonal Antibodies for the Preventative Treatment of Migraine.","authors":"Israel, Heike; Neeb, Lars; Reuter, Uwe","year":2018,"journal":"Current pain and headache reports, 22(5), 38","doi":"10.1007/s11916-018-0686-4","pmid":"29623520","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03723","title":"Antigenic Peptide Prediction From E6 and E7 Oncoproteins of HPV Types 16 and 18 for Therapeutic Vaccine Design Using Immunoinformatics and MD Simulation Analysis.","authors":"Jabbar, Basit; Rafique, Shazia; Salo-Ahen, Outi M H; Ali, Amjad; Munir, Mobeen; Idrees, Muhammad; Mirza, Muhammad Usman; Vanmeert, Michiel; Shah, Syed Zawar; Jabbar, Iqra; Rana, Muhammad Adeel","year":2018,"journal":"Frontiers in immunology, 9, 3000","doi":"10.3389/fimmu.2018.03000","pmid":"30619353","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03724","title":"Optimized Gemcitabine Therapy in Combination with E7 Peptide Immunization Elicits Tumor Cure by Preventing Ag-Specific CTL Inhibition in Animals with Large Established Tumors.","authors":"Jang, Ho-Young; Han, Baek-Sang; Kwon, Byungsuk; Sin, Jeong-Im","year":2018,"journal":"DNA and cell biology, 37(10), 850-860","doi":"10.1089/dna.2018.4319","pmid":"30227079","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03725","title":"Falsification of biotechnology drugs: current dangers and/or future disasters?","authors":"Janvier, Steven; De Spiegeleer, Bart; Vanhee, Celine; Deconinck, Eric","year":2018,"journal":"Journal of pharmaceutical and biomedical analysis, 161, 175-191","doi":"10.1016/j.jpba.2018.08.037","pmid":"30165334","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03726","title":"Impurity profiling of the most frequently encountered falsified polypeptide drugs on the Belgian market.","authors":"Janvier, Steven; Cheyns, Karlien; Canfyn, Michaël; Goscinny, Séverine; De Spiegeleer, Bart; Vanhee, Celine; Deconinck, Eric","year":2018,"journal":"Talanta, 188, 795-807","doi":"10.1016/j.talanta.2018.06.023","pmid":"30029448","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Systematic screening of the 10 most frequently falsified peptide drugs from three suspected illegal internet pharmacies revealed:\n\nPurity: ranged between 5% and 75% for cysteine-containing peptides — meaning up to 95% of some products were impurities rather than the intended drug\n\nElemental impurities:\n- Multiple samples contained arsenic (As) at concentrations up to 10x the ICH toxicity limit for parenteral (injectable) drugs\n- All arsenic was present in the more toxic inorganic form (confirmed by speciation analysis)\n- One sample was contaminated with lead (Pb)\n\nOther concerns: high variation in drug amount per unit, significant peptide-related impurities, and the presence of residual solvents from manufacturing\n\nThe study also flagged the inherent danger of some products being doping peptides or preclinical drugs not approved for human use.","whyItMatters":"The black market for peptide drugs is booming — driven by demand for research peptides, performance-enhancing compounds, and medications that are expensive through legitimate channels. Because these products are injected directly into the body, contamination with toxic metals like arsenic and lead is far more dangerous than in oral supplements. The finding of a known carcinogen at 10x safety limits in injectable products represents a genuine public health hazard, especially given that many users self-administer these peptides regularly over long periods.","specificNumbers":"","methodology":"The ten most frequently encountered falsified peptide drugs were acquired from three different suspected illegal internet pharmacies on the Belgian market. Systematic screening incorporated five analytical dimensions: active pharmaceutical ingredient (API) content, API-related impurities, small molecule contaminants, elemental impurity analysis (including arsenic and lead), and residual solvent analysis. Arsenic speciation was performed to determine whether arsenic was in its more toxic inorganic form or less toxic organic form.","limitations":"The study examined products from the Belgian market, and contamination profiles may differ in other countries. Only three online sources were sampled. The specific peptide drug names are not listed in the abstract, limiting the ability to advise on specific products. The study assesses chemical contamination but does not report biological contamination (bacterial endotoxins, viruses) that could also pose risks in injectable products. Long-term health outcomes in users of these contaminated products are not tracked."},{"rthcId":"RPEP-03727","title":"Pyrimidine synthesis inhibition enhances cutaneous defenses against antibiotic resistant bacteria through activation of NOD2 signaling.","authors":"Jatana, Samreen; Homer, Craig R; Madajka, Maria; Ponti, András K; Kabi, Amrita; Papay, Francis; McDonald, Christine","year":2018,"journal":"Scientific reports, 8(1), 8708","doi":"10.1038/s41598-018-27012-0","pmid":"29880914","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03728","title":"Antimicrobial peptide delivery: an emerging therapeutic for the treatment of burn and wounds.","authors":"Javia, Ankit; Amrutiya, Jitendra; Lalani, Rohan; Patel, Vivek; Bhatt, Priyanka; Misra, Ambikanandan","year":2018,"journal":"Therapeutic delivery, 9(5), 375-386","doi":"10.4155/tde-2017-0061","pmid":"29681237","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03729","title":"Structural Motif Descriptors as a Way To Elucidate the Agonistic or Antagonistic Activity of Growth Hormone-Releasing Hormone Peptide Analogues.","authors":"Jeanne Dit Fouque, Kevin; Salgueiro, Luis M; Cai, Renzhi; Sha, Wei; Schally, Andrew V; Fernandez-Lima, Francisco","year":2018,"journal":"ACS omega, 3(7), 7432-7440","doi":"10.1021/acsomega.8b00375","pmid":"31458901","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03730","title":"MK-0677, a Ghrelin Agonist, Alleviates Amyloid Beta-Related Pathology in 5XFAD Mice, an Animal Model of Alzheimer's Disease.","authors":"Jeong, Yu-On; Shin, Soo Jung; Park, Jun Yong; Ku, Bo Kyeong; Song, Ji Soo; Kim, Jwa-Jin; Jeon, Seong Gak; Lee, Sang Min; Moon, Minho","year":2018,"journal":"International journal of molecular sciences, 19(6)","doi":"10.3390/ijms19061800","pmid":"29912176","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03731","title":"A new approach to the treatment of acute myeloid leukaemia targeting the receptor for growth hormone-releasing hormone.","authors":"Jimenez, Joaquin J; DelCanto, Gina M; Popovics, Petra; Perez, Aymee; Vila Granda, Ailin; Vidaurre, Irving; Cai, Ren-Zhi; Rick, Ferenc G; Swords, Ronan T; Schally, Andrew V","year":2018,"journal":"British journal of haematology, 181(4), 476-485","doi":"10.1111/bjh.15207","pmid":"29663325","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03732","title":"The now and then of gut-brain signaling.","authors":"Kaelberer, Melanie M; Bohórquez, Diego V","year":2018,"journal":"Brain research, 1693(Pt B), 192-196","doi":"10.1016/j.brainres.2018.03.027","pmid":"29580839","tags":[],"studyType":"review","evidenceStrength":"low-moderate","keyFinding":"New single-cell molecular tools have revealed that gut sensory cells (enteroendocrine cells) are far more complex than previously thought. Key discoveries include: individual gut sensor cells can express both ghrelin and cholecystokinin — opposing appetite hormones — simultaneously, challenging the old 'one cell, one hormone' model. These cells are also capable of multimodal sensing and form direct synapses with nerves, providing a fast neural pathway for gut-to-brain signaling alongside slower hormonal communication.\n\nThe evolutionary perspective reveals that gut sensory epithelial cells are among the most ancient cell types, present even in Trichoplax, one of the first multicellular organisms.","whyItMatters":"Understanding how the gut talks to the brain is fundamental to appetite regulation, obesity, and the mechanisms behind GLP-1 drugs. The discovery that single gut cells can express opposing appetite peptides and form direct nerve connections redefines our model of gut-brain signaling — from slow hormonal broadcasting to fast, nuanced neural communication.","specificNumbers":"Gut sensory cells since Trichoplax · Single cells expressing both ghrelin + CCK · Direct synapses with nerves · 150+ years since Heidenhain's 'clear cells' (1868)","methodology":"Brief narrative review examining the evolutionary history and recent molecular biology advances in gut sensory transduction. Covers new single-cell tools revealing multimodal sensing, co-expression of opposing neuropeptides, and synaptic connections in enteroendocrine cells.","limitations":"This is a brief perspective/mini-review rather than a comprehensive systematic review. Many of the described findings were recent at the time of publication and needed further validation. The functional implications of co-expressing opposing appetite peptides in single cells remain speculative."},{"rthcId":"RPEP-03733","title":"Folate Receptor Alpha Peptide Vaccine Generates Immunity in Breast and Ovarian Cancer Patients.","authors":"Kalli, Kimberly R; Block, Matthew S; Kasi, Pashtoon M; Erskine, Courtney L; Hobday, Timothy J; Dietz, Allan; Padley, Douglas; Gustafson, Michael P; Shreeder, Barath; Puglisi-Knutson, Danell; Visscher, Dan W; Mangskau, Toni K; Wilson, Glynn; Knutson, Keith L","year":2018,"journal":"Clinical cancer research : an official journal of the American Association for Cancer Research, 24(13), 3014-3025","doi":"10.1158/1078-0432.CCR-17-2499","pmid":"29545464","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A peptide vaccine targeting folate receptor alpha (FR) was safe and elicited or augmented immune responses in more than 90% of breast and ovarian cancer patients in a phase I trial. The vaccine used HLA-class II epitopes designed for broad population coverage regardless of HLA genotype. FR-specific T cell responses developed slowly (median 5 months to peak) but persisted for at least 12 months after vaccination. All patients tolerated the vaccine well, with no serious safety concerns.","whyItMatters":"Folate receptor alpha is overexpressed in multiple cancers, making it an attractive vaccine target. This phase I trial demonstrated that a peptide vaccine can safely generate sustained immunity against this tumor marker in the majority of patients. The broad HLA coverage means most patients are eligible, overcoming a major limitation of many peptide cancer vaccines. The 12-month immune persistence suggests potential for long-lasting cancer surveillance.","specificNumbers":">90% immune response rate · 6 monthly vaccinations · Median 5 months to peak immunity · Immunity persisted ≥12 months · Breast + ovarian cancer patients · Low-dose cyclophosphamide priming · Phase I trial","methodology":"Phase I clinical trial enrolling breast and ovarian cancer patients who completed conventional treatment with no evidence of disease. Patients received low-dose cyclophosphamide followed by 6 monthly vaccinations with FR peptide epitope pool. Immune responses (FR-specific T cells) and safety were assessed during vaccination and for up to 1 year. Tetanus toxoid responses served as an immune function control.","limitations":"Phase I trial — designed to test safety and immunogenicity, not therapeutic efficacy. Sample size not specified in abstract. No control group (single-arm design). All patients had no evidence of disease at enrollment, so relapse prevention cannot be assessed from this trial alone. The slow immune response development (5 months) means patients need sustained vaccination commitment."},{"rthcId":"RPEP-03734","title":"Folate Receptor Alpha Peptide Vaccine Generates Immunity in Breast and Ovarian Cancer Patients.","authors":"Kalli, Kimberly R; Block, Matthew S; Kasi, Pashtoon M; Erskine, Courtney L; Hobday, Timothy J; Dietz, Allan; Padley, Douglas; Gustafson, Michael P; Shreeder, Barath; Puglisi-Knutson, Danell; Visscher, Dan W; Mangskau, Toni K; Wilson, Glynn; Knutson, Keith L","year":2018,"journal":"Clinical cancer research : an official journal of the American Association for Cancer Research, 24(13), 3014-3025","doi":"10.1158/1078-0432.CCR-17-2499","pmid":"29545464","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03735","title":"Characterization of membrane penetration and cytotoxicity of C9orf72-encoding arginine-rich dipeptides.","authors":"Kanekura, Kohsuke; Harada, Yuichiro; Fujimoto, Mao; Yagi, Takuya; Hayamizu, Yuhei; Nagaoka, Kentaro; Kuroda, Masahiko","year":2018,"journal":"Scientific reports, 8(1), 12740","doi":"10.1038/s41598-018-31096-z","pmid":"30143685","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03736","title":"Water-based extracts of Zizania latifolia inhibit Staphylococcus aureus infection through the induction of human beta-defensin 2 expression in HaCaT cells.","authors":"Kang, Bo Yeon; Lee, Seung-Su; Bang, Myun-Ho; Jeon, Hyoik; Kim, Hangeun; Chung, Dae Kyun","year":2018,"journal":"Journal of microbiology (Seoul, Korea), 56(12), 910-916","doi":"10.1007/s12275-018-8307-9","pmid":"30484159","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03737","title":"BPC157 as Potential Agent Rescuing from Cancer Cachexia.","authors":"Kang, Eun A; Han, Young-Min; An, Jeong Min; Park, Yong Jin; Sikiric, Predrag; Kim, Deok Hwan; Kwon, Kwang An; Kim, Yoon Jae; Yang, Donghwa; Tchah, Hann; Hahm, Ki Baik","year":2018,"journal":"Current pharmaceutical design, 24(18), 1947-1956","doi":"10.2174/1381612824666180614082950","pmid":"29898649","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"This review proposes BPC157, a cytoprotective peptide isolated from gastric juices, as a potential therapeutic agent for cancer cachexia. The authors present preclinical evidence that BPC157 may rescue from cancer cachexia through its explored modes of action, positioning it as a candidate for clinical trials.","whyItMatters":"Cancer cachexia affects over 50% of terminal cancer patients and accounts for up to 20% of cancer deaths, yet no effective treatment exists. Identifying a novel peptide-based therapeutic candidate like BPC157 could address this urgent unmet medical need.","specificNumbers":"50% of terminal cancer patients affected · up to 20% of cancer deaths attributable to cachexia","methodology":"Literature review synthesizing preclinical evidence for BPC157 in cancer cachexia, including exploration of its mechanisms of action.","limitations":"This is a review paper proposing BPC157 as a candidate, not a clinical trial. The evidence presented is preclinical and has not yet been validated in human studies."},{"rthcId":"RPEP-03738","title":"Transdermal delivery system of nanostructured lipid carriers loaded with Celastrol and Indomethacin: optimization, characterization and efficacy evaluation for rheumatoid arthritis.","authors":"Kang, Qian; Liu, Jia; Zhao, Ying; Liu, Xin; Liu, Xin-Yan; Wang, Yong-Jie; Mo, Nuo-Lan; Wu, Qing","year":2018,"journal":"Artificial cells, nanomedicine, and biotechnology, 46(sup3), S585-S597","doi":"10.1080/21691401.2018.1503599","pmid":"30306802","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03739","title":"Cell-penetrating artificial mitochondria-targeting peptide-conjugated metallothionein 1A alleviates mitochondrial damage in Parkinson's disease models.","authors":"Kang, Young Cheol; Son, Minuk; Kang, Sora; Im, Suyeol; Piao, Ying; Lim, Kwang Suk; Song, Min-Young; Park, Kang-Sik; Kim, Yong-Hee; Pak, Youngmi Kim","year":2018,"journal":"Experimental & molecular medicine, 50(8), 1-13","doi":"10.1038/s12276-018-0124-z","pmid":"30120245","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03740","title":"Stapled truncated orexin peptides as orexin receptor agonists.","authors":"Karhu, Lasse; Weisell, Janne; Turunen, Pauli M; Leino, Teppo O; Pätsi, Henri; Xhaard, Henri; Kukkonen, Jyrki P; Wallén, Erik A A","year":2018,"journal":"Peptides, 102, 54-60","doi":"10.1016/j.peptides.2018.02.004","pmid":"29475074","tags":["peptide-stapling","orexin"],"studyType":"in-vitro-study","evidenceStrength":"preliminary","keyFinding":"Researchers used peptide stapling — a chemical technique that locks a peptide into a helical shape — on shortened versions of orexin-A to try to maintain their biological activity. The stapled peptides did activate orexin receptors, proving that the receptors can accommodate and respond to rigidly helical peptides. However, all stapled variants had reduced potency compared to the unmodified truncated peptide.\n\nStapling near the C-terminus (the business end of the peptide) completely killed activity. Central and N-terminal stapling positions kept the peptides active but weaker, likely because the rigid helix locked the peptide into a shape that wasn't quite optimal for receptor binding.","whyItMatters":"Orexin peptides regulate wakefulness and appetite, making them potential drug targets for narcolepsy and metabolic disorders. But natural orexin peptides are too large and unstable for practical drug use. Peptide stapling is a promising strategy to create smaller, more stable versions. This study shows the approach is feasible — stapled orexin peptides can still activate the receptor — but highlights the challenge of maintaining potency when you constrain a peptide's shape.","specificNumbers":"19-amino-acid C-terminal fragment used · 4 stapling sites tested · orexin-A15-33 as starting peptide · α-aminoisobutyric acid substitutions also tested","methodology":"The researchers took orexin-A15-33 (a 19-amino-acid fragment that retains full activity) and introduced hydrocarbon staples at four different positions along the peptide. They also tested replacing the staple with α-aminoisobutyric acid (Aib) residues at a suspected hinge region. All variants were tested for their ability to activate orexin receptors in cell-based assays measuring intracellular signaling.","limitations":"This is an in-vitro study measuring receptor activation in cells, not in living animals. The stapled peptides all showed reduced potency, so the practical utility of this specific approach remains unclear. Stability improvements from stapling (resistance to degradation) were not directly measured in this study."},{"rthcId":"RPEP-03741","title":"Synthetic molecular evolution of hybrid cell penetrating peptides.","authors":"Kauffman, W Berkeley; Guha, Shantanu; Wimley, William C","year":2018,"journal":"Nature communications, 9(1), 2568","doi":"10.1038/s41467-018-04874-6","pmid":"29967329","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03742","title":"Intranasal oxytocin, social cognition and neurodevelopmental disorders: A meta-analysis.","authors":"Keech, Britney; Crowe, Simon; Hocking, Darren R","year":2018,"journal":"Psychoneuroendocrinology, 87, 9-19","doi":"10.1016/j.psyneuen.2017.09.022","pmid":"29032324","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 17 RCTs with 466 participants with neurodevelopmental disorders, intranasal oxytocin showed:\n\n- Emotion recognition: no significant effect (Hedges' g = 0.08 — essentially zero)\n- Empathy: moderate but non-significant effect (Hedges' g = 0.49)\n- Theory of mind: small, significant effect (Hedges' g = 0.21)\n\nMeta-regression found that none of the moderating variables — diagnosis type, participant age, oxytocin dose, or frequency of administration — predicted treatment response. This uniformly modest-to-null result across different conditions and dosing approaches suggests a fundamental limitation rather than a design problem that could be solved with optimization.","whyItMatters":"Intranasal oxytocin has been one of the most-hyped potential treatments for autism and related conditions, generating enormous public interest and research investment. This meta-analysis provides a needed reality check: the aggregate evidence from well-designed trials shows minimal clinical benefit. For families and clinicians, this is important because oxytocin nasal sprays are sometimes obtained off-label with high hopes and significant expense. The results suggest that more research is needed before intranasal oxytocin can be recommended as a treatment for social cognition deficits.","specificNumbers":"","methodology":"Systematic search of Medline, PsychINFO, and Scopus for randomized controlled trials of intranasal oxytocin on social cognition in neurodevelopmental disorders, published through July 2017. Seventeen studies met inclusion criteria (466 total participants). Meta-analysis used a random-effects model with Hedges' g as the effect size measure. Meta-regression examined potential moderators including diagnosis, age, dose, and frequency.","limitations":"The included studies were heterogeneous in design, NDD diagnosis (autism spectrum disorder, intellectual disability, Prader-Willi syndrome, etc.), outcome measures, and oxytocin dosing protocols. The total sample of 466 participants across 17 studies yields relatively low statistical power for subgroup analyses. Studies published after July 2017 are not included. The meta-analysis could not assess long-term effects, as most studies used single-dose or short-term protocols. Publication bias, while not formally assessed in the abstract, could affect results."},{"rthcId":"RPEP-03743","title":"Disturbance of gut satiety peptide in purging disorder.","authors":"Keel, Pamela K; Eckel, Lisa A; Hildebrandt, Britny A; Haedt-Matt, Alissa A; Appelbaum, Jonathan; Jimerson, David C","year":2018,"journal":"The International journal of eating disorders, 51(1), 53-61","doi":"10.1002/eat.22806","pmid":"29219202","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03744","title":"Effects of teriparatide and risedronate on new fractures in post-menopausal women with severe osteoporosis (VERO): a multicentre, double-blind, double-dummy, randomised controlled trial.","authors":"Kendler, David L; Marin, Fernando; Zerbini, Cristiano A F; Russo, Luis A; Greenspan, Susan L; Zikan, Vit; Bagur, Alicia; Malouf-Sierra, Jorge; Lakatos, Péter; Fahrleitner-Pammer, Astrid; Lespessailles, Eric; Minisola, Salvatore; Body, Jean Jacques; Geusens, Piet; Möricke, Rüdiger; López-Romero, Pedro","year":2018,"journal":"Lancet (London, England), 391(10117), 230-240","doi":"10.1016/S0140-6736(17)32137-2","pmid":"29129436","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03745","title":"Overview of Human Oxytocin Research.","authors":"Kendrick, Keith M; Guastella, Adam J; Becker, Benjamin","year":2018,"journal":"Current topics in behavioral neurosciences, 35, 321-348","doi":"10.1007/7854_2017_19","pmid":"28864976","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03746","title":"MRI assessment of the postprandial gastrointestinal motility and peptide response in healthy humans.","authors":"Khalaf, A; Hoad, C L; Menys, A; Nowak, A; Taylor, S A; Paparo, S; Lingaya, M; Falcone, Y; Singh, G; Spiller, R C; Gowland, P A; Marciani, L; Moran, G W","year":2018,"journal":"Neurogastroenterology and motility, 30(1)","doi":"10.1111/nmo.13182","pmid":"28857333","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03747","title":"Expression of Gastrin Family Peptides in Pancreatic Islets and Their Role in β-Cell Function and Survival.","authors":"Khan, Dawood; Vasu, Srividya; Moffett, R Charlotte; Irwin, Nigel; Flatt, Peter R","year":2018,"journal":"Pancreas, 47(2), 190-199","doi":"10.1097/MPA.0000000000000983","pmid":"29329158","tags":["gut-peptides","diabetes"],"studyType":"Preclinical Study (Cell + Animal)","evidenceStrength":"Low-Moderate","keyFinding":"Gastrin family peptides — specifically a modified CCK fragment called (pGlu-Gln)-CCK-8 and gastrin-17 — directly stimulate insulin secretion from pancreatic beta cells and promote beta-cell growth and survival. In cell studies, both peptides increased insulin release and boosted beta-cell proliferation while protecting against toxic damage. In live mice, (pGlu-Gln)-CCK-8 improved glucose disposal, enhanced insulin release, and reduced appetite.\n\nThe study also revealed that diabetes changes how CCK and gastrin are expressed in pancreatic islets: in diabetic mice, CCK shifted toward glucagon-producing alpha cells while gastrin shifted toward insulin-producing beta cells, suggesting these peptide systems actively adapt during disease.","whyItMatters":"Preserving and regenerating insulin-producing beta cells is the holy grail of diabetes treatment. This study shows that two gut peptides already known for digestive functions — CCK and gastrin — can directly support beta-cell health and insulin production. If these peptide pathways can be harnessed therapeutically, they could offer a fundamentally different approach to diabetes: not just managing blood sugar, but protecting and restoring the cells that make insulin.","specificNumbers":"","methodology":"The researchers used a multi-level approach: first confirming that CCK and gastrin receptors are present in beta-cell lines (BRIN-BD11 and 1.1B4) and mouse pancreatic islets, then testing the effects of (pGlu-Gln)-CCK-8 and gastrin-17 on insulin secretion, cell proliferation, and protection against chemically induced cell death. In vivo experiments in mice tested the effects on glucose tolerance and insulin release. They also examined how CCK and gastrin expression patterns change in two mouse models of diabetes (streptozotocin-induced and hydrocortisone-induced).","limitations":"This is a preclinical study combining cell culture and mouse experiments — results may not translate directly to humans. The beta-cell lines used are models, not primary human cells. The diabetic mouse models (chemically induced) may not perfectly replicate the complexity of human type 1 or type 2 diabetes. The satiety effects were observed in mice and would need human confirmation. Long-term effects and safety of modulating these peptide pathways are unknown."},{"rthcId":"RPEP-03748","title":"Toxicity of Biologically Active Peptides and Future Safety Aspects: An Update.","authors":"Khan, Fazlullah; Niaz, Kamal; Abdollahi, Mohammad","year":2018,"journal":"Current drug discovery technologies, 15(3), 236-242","doi":"10.2174/1570163815666180219112806","pmid":"29468976","tags":["peptide-safety","toxicology"],"studyType":"review","evidenceStrength":"low","keyFinding":"While most manufactured bioactive peptides show negligible toxicity, some naturally occurring peptides and enzymes can induce significant toxicity. The review identifies six main safety concerns with biologically active peptides: intestinal wall disruption, erythrocyte and lymphocyte toxicity, free radical production, enzyme-mediated tissue damage, immune-mediated tissue damage, and direct cytotoxicity.\n\nThe authors advocate for systematic safety evaluation — particularly using in silico (computational) methods — before peptides are used in food production or pharmaceutical applications. They emphasize that both immunogenicity (immune reactions against the peptide itself) and direct toxicity need assessment, as the growing use of peptides across food, cosmetics, and medicine demands standardized safety protocols.","whyItMatters":"As peptides move from research labs into foods, cosmetics, and drugs, the assumption that 'natural means safe' can be dangerous. This review serves as a needed reality check — bioactive peptides have real biological effects, and those effects can include harm if not properly evaluated. With the peptide supplement market booming and minimal regulatory oversight in some sectors, understanding potential toxicity mechanisms is critical for consumer safety.","specificNumbers":"6 toxicity mechanisms identified · in silico safety screening recommended · food + cosmetics + pharmaceutical applications reviewed","methodology":"Systematic literature review searching PubMed, Google Scholar, Medline, EMBASE, Reaxys, and Scopus databases for research and review articles on toxicity of biologically active peptides.","limitations":"The review is broad but not deep — covering many types of peptide toxicity without detailed quantitative analysis of any specific category. Much of the toxicity data comes from isolated cell studies rather than whole-organism or clinical observations. The in silico safety prediction tools recommended are still developing and may not capture all toxicity mechanisms."},{"rthcId":"RPEP-03749","title":"Biomarker potential of C-peptide for screening of insulin resistance in diabetic and non-diabetic individuals.","authors":"Khan, Haseeb A; Sobki, Samia H; Ekhzaimy, Aishah; Khan, Isra; Almusawi, Mona A","year":2018,"journal":"Saudi journal of biological sciences, 25(8), 1729-1732","doi":"10.1016/j.sjbs.2018.05.027","pmid":"30591792","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03750","title":"Oral Intake of Low-Molecular-Weight Collagen Peptide Improves Hydration, Elasticity, and Wrinkling in Human Skin: A Randomized, Double-Blind, Placebo-Controlled Study.","authors":"Kim, Do-Un; Chung, Hee-Chul; Choi, Jia; Sakai, Yasuo; Lee, Boo-Yong","year":2018,"journal":"Nutrients, 10(7)","doi":"10.3390/nu10070826","pmid":"29949889","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Compared to placebo, low-molecular-weight collagen peptide (LMWCP) supplementation at 1,000 mg/day for 12 weeks showed:\n- Significantly higher skin hydration at both 6 weeks and 12 weeks\n- Significantly improved visual wrinkle assessment score at 12 weeks\n- Three out of three skin wrinkling parameters significantly improved at 12 weeks\n- Two out of three skin elasticity parameters significantly improved versus placebo at 12 weeks\n- One elasticity parameter improved within the LMWCP group from baseline\n- Zero adverse events reported throughout the study\n\nThe collagen peptides contained >15% Gly-X-Y tripeptide content including 3% Gly-Pro-Hyp, which are the bioactive sequences thought to stimulate skin collagen production.","whyItMatters":"The collagen supplement market is valued at billions of dollars, but much of the marketing outpaces the evidence. This study provides rigorous clinical trial evidence — the gold standard of double-blind, placebo-controlled design — showing that specific low-molecular-weight collagen peptides do measurably improve skin properties. The characterization of the peptide composition (>15% Gly-X-Y tripeptides) also helps consumers and clinicians identify which collagen products might actually work.","specificNumbers":"","methodology":"Double-blind, randomized, placebo-controlled trial. 64 participants were randomly assigned to receive 1,000 mg LMWCP or placebo once daily for 12 weeks. Skin hydration, wrinkling (visual and instrumental), and elasticity were assessed at baseline, 6 weeks, and 12 weeks. Safety was monitored throughout.","limitations":"The sample size (64 participants) is relatively small, and the study duration (12 weeks) is moderate. The participant demographics (age range, sex distribution) are not detailed in the abstract. The study does not include histological or biochemical data to confirm that the measured improvements correspond to actual changes in skin collagen content. The single dose tested (1,000 mg) prevents understanding of dose-response relationships. Long-term maintenance of benefits after stopping supplementation was not assessed."},{"rthcId":"RPEP-03751","title":"Engineering of a tumor cell-specific, cytosol-penetrating antibody with high endosomal escape efficacy.","authors":"Kim, Ji-Sun; Park, Jae-Yeong; Shin, Seung-Min; Park, Seong-Wook; Jun, Sei-Yong; Hong, Jin-Sun; Choi, Dong-Ki; Kim, Yong-Sung","year":2018,"journal":"Biochemical and biophysical research communications, 503(4), 2510-2516","doi":"10.1016/j.bbrc.2018.07.008","pmid":"30208519","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The engineering process involved several innovations:\n\n1. Reduced non-specific cell binding by lowering HSPG-binding activity of the parent antibody\n2. Added tumor specificity by fusing a cyclic peptide recognizing EpCAM (a tumor-associated marker) to the antibody's light chain\n3. Engineered endosomal escape motifs into both the heavy chain (VH) and light chain (VL) variable domains\n4. The final construct, epCT65, effectively localized to the cytosol of only EpCAM-expressing tumor cells\n5. Achieved approximately 2-fold improved endosomal escape efficiency compared to constructs with escape motifs in either VH or VL alone\n6. Maintained full IgG format, preserving stability and potential for clinical development","whyItMatters":"Most cancer-targeting antibodies work by binding to the outside of cancer cells. But many important cancer targets — transcription factors, signaling proteins, protein-protein interactions — are inside the cell. This peptide-antibody hybrid addresses both the specificity problem (hitting only cancer cells) and the delivery problem (actually reaching the cell interior) in a single molecule, which could unlock an entire class of previously inaccessible intracellular cancer targets.","specificNumbers":"","methodology":"Protein engineering study using iterative antibody modification. The parent cytotransmab (TMab4-WYW) was modified to reduce non-specific binding, then fused with an EpCAM-targeting cyclic peptide. Endosomal escape motifs were engineered into both variable domains through functional grafting. Cell penetration, tumor specificity, and cytosolic localization were confirmed using fluorescence microscopy and functional assays in EpCAM-positive and EpCAM-negative cell lines.","limitations":"All experiments were conducted in cell lines — no animal studies or human data are reported. The 2-fold improvement in endosomal escape, while significant, may still leave much of the antibody trapped in endosomes. Long-term stability and in vivo pharmacokinetics of the chimeric construct are unknown. EpCAM is expressed on some normal epithelial cells, so tumor specificity may not be absolute. No therapeutic payload was tested — only the delivery vehicle was validated."},{"rthcId":"RPEP-03752","title":"Human β-defensin 2 plays a regulatory role in innate antiviral immunity and is capable of potentiating the induction of antigen-specific immunity.","authors":"Kim, Ju; Yang, Ye Lin; Jang, Sun-Hee; Jang, Yong-Suk","year":2018,"journal":"Virology journal, 15(1), 124","doi":"10.1186/s12985-018-1035-2","pmid":"30089512","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03753","title":"The Mitochondrial-Encoded Peptide MOTS-c Translocates to the Nucleus to Regulate Nuclear Gene Expression in Response to Metabolic Stress.","authors":"Kim, Kyung Hwa; Son, Jyung Mean; Benayoun, Bérénice A; Lee, Changhan","year":2018,"journal":"Cell metabolism, 28(3), 516-524.e7","doi":"10.1016/j.cmet.2018.06.008","pmid":"29983246","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03754","title":"Long-pulsed 1064-nm Nd: YAG laser ameliorates LL-37-induced rosacea-like skin lesions through promoting collagen remodeling in BALB/c mice.","authors":"Kim, Miri; Kim, Jongsic; Jeong, Seo-Won; Jo, Hyunmu; Park, Hyun Jeong","year":2018,"journal":"Lasers in medical science, 33(2), 393-397","doi":"10.1007/s10103-017-2410-8","pmid":"29256058","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Long-pulsed 1064-nm Nd:YAG laser treatment significantly reduced erythema (redness) and increased dermal collagen production in LL-37-induced rosacea-like skin lesions. Laser-treated mice showed significantly higher mRNA levels of type I collagen, TGF-β (a growth factor that promotes tissue repair), and MMP-1 (an enzyme that breaks down damaged collagen) compared to untreated mice.\n\nThese results suggest the laser works by triggering MMP-mediated collagen remodeling — essentially clearing out disorganized connective tissue and replacing it with healthy new collagen, which addresses the dermal damage underlying rosacea rather than just treating surface symptoms.","whyItMatters":"This study provides molecular evidence for why Nd:YAG laser therapy works for rosacea, a condition affecting an estimated 5% of the global population. By showing that the laser promotes collagen remodeling rather than just reducing surface redness, it supports the use of laser treatment to address deeper structural skin damage in rosacea. It also reinforces the central role of LL-37 in rosacea pathology.","specificNumbers":"","methodology":"Researchers injected the cathelicidin peptide LL-37 intradermally into the dorsal skin of 30 BALB/c mice twice daily for 2 days to induce rosacea-like lesions. Fifteen mice were then treated with long-pulsed Nd:YAG laser. After 48 hours, skin samples were excised and analyzed using histology, collagen staining, and real-time RT-PCR to measure mRNA levels of type I collagen, TGF-β, MMP-1, TIMP-1, TNF-α, and IL-1α.","limitations":"This was a mouse study using an artificial rosacea model (intradermal LL-37 injection), which may not fully replicate the chronic, multifactorial nature of human rosacea. The sample size was small (30 mice total), the observation period was short (48 hours post-treatment), and the study measured mRNA expression rather than long-term clinical outcomes. Mouse skin differs structurally from human facial skin."},{"rthcId":"RPEP-03755","title":"Bifunctional peptide hybrids targeting the matrix of mitochondria.","authors":"Klimpel, Annika; Neundorf, Ines","year":2018,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 291, 147-156","doi":"10.1016/j.jconrel.2018.10.029","pmid":"30367921","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Researchers created bifunctional hybrid peptides by combining a mitochondrial targeting sequence (MTS) with the cell-penetrating peptide sC18. Not all MTS sequences were equally effective — careful selection was critical. The CPP sC18 served a dual role, driving both cellular uptake and sub-organelle entry into the mitochondrial matrix.\n\nWhen conjugated to the cancer drug chlorambucil, the optimized hybrid peptide enhanced intracellular drug delivery, demonstrating its potential as a mitochondria-targeted drug carrier for cancer and other mitochondrial diseases.","whyItMatters":"Mitochondrial dysfunction underlies many diseases including cancer, diabetes, and neurodegenerative disorders, but delivering drugs specifically to mitochondria inside living cells is extremely difficult. This peptide-based delivery system solves two problems at once — getting into cells and then reaching mitochondria — using a simple, modular peptide design that could be adapted for various therapeutic payloads.","specificNumbers":"2 functional components (MTS + CPP sC18) · Multiple MTS sequences tested · Enhanced chlorambucil uptake demonstrated · HeLa and MCF-7 cancer cell lines tested","methodology":"The researchers designed hybrid peptides by linking different mitochondrial targeting sequences to the cell-penetrating peptide sC18. They tested cellular uptake and mitochondrial localization in HeLa and MCF-7 cancer cell lines using fluorescence microscopy and quantitative uptake assays. Drug delivery capability was assessed by conjugating chlorambucil to the optimized peptide and measuring enhanced intracellular uptake and cytotoxicity.","limitations":"All experiments were conducted in vitro using cancer cell lines, which may not reflect behavior in whole organisms. The study focused on proof-of-concept with chlorambucil — only one drug payload was tested. In vivo pharmacokinetics, stability, toxicity, and biodistribution of the hybrid peptides remain unknown."},{"rthcId":"RPEP-03756","title":"Amino acid composition of nanofibrillar self-assembling peptide hydrogels affects responses of periodontal tissue cells in vitro.","authors":"Koch, Franziska; Wolff, Anne; Mathes, Stephanie; Pieles, Uwe; Saxer, Sina S; Kreikemeyer, Bernd; Peters, Kirsten","year":2018,"journal":"International journal of nanomedicine, 13, 6717-6733","doi":"10.2147/IJN.S173702","pmid":"30425485","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Four 11-amino acid self-assembling peptide (P11-SAP) hydrogels were compared for their scaffold properties and effects on periodontal cells.\n\nSingle-component P11-SAP systems demonstrated:\n- ~30% higher porosity than complementary systems\n- Almost 2-fold higher protein adsorption\n- 1.7-fold increase in cell adhesion and cellular growth versus complementary systems\n- Significantly enhanced osteogenic (bone-forming) differentiation of human calvarial osteoblasts compared to standard culture surfaces\n\nAll four hydrogels were cytocompatible, with cell responses similar to standard culture surfaces. The differences in properties were directly attributable to amino acid composition, demonstrating rational design capability.","whyItMatters":"Periodontal disease is the leading cause of tooth loss worldwide, and regenerating the destroyed tissue interface between gums and bone remains an unsolved clinical problem. Self-assembling peptides offer a unique advantage: they can be rationally designed at the amino acid level to match specific tissue requirements, and they form nanofiber networks that closely mimic the body's natural extracellular matrix. The ability to enhance both cell adhesion and bone formation from a simple peptide scaffold could lead to injectable treatments for periodontal defects.","specificNumbers":"","methodology":"Four 11-amino-acid self-assembling peptide (P11-SAP) systems — two single-component and two complementary β-sheet forming — were synthesized and characterized. Nanofibrillar architecture, surface charge, and protein adsorption were measured. In vitro biological assays used periodontal tissue cells to assess cell adhesion, morphology, growth, and osteogenic differentiation. Human calvarial osteoblasts were used for differentiation studies.","limitations":"This is an in vitro study — cell culture results may not fully predict performance in the complex in vivo periodontal environment. No animal studies or clinical data are presented. Only four peptide compositions were tested; the design space for 11-amino-acid peptides is much larger. Mechanical properties under physiological loading (chewing forces) were not assessed. Degradation kinetics and long-term stability of the hydrogels in the oral environment need investigation. The cost of synthesizing clinical-grade self-assembling peptides at scale was not addressed."},{"rthcId":"RPEP-03757","title":"MALT Lymphoma, Stress Ulcer and Cholinergic Nerves from the Viewpoint of Bilateral and Unilateral Truncal Vagotomy and Substance P.","authors":"Kodama, Yosuke; Sasaki, Kazuki; Murasato, Futa; Overby, Anders; Takahashi, Shinichi; Murayama, Somay Y; Matsui, Hidenori; Nakamura, Masahiko","year":2018,"journal":"Current pharmaceutical design, 24(18), 1961-1965","doi":"10.2174/1381612824666180516103027","pmid":"29766790","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03758","title":"Post-Exercise Whole Body Cryotherapy (-140 °C) Increases Energy Intake in Athletes.","authors":"Kojima, Chihiro; Kasai, Nobukazu; Kondo, Chika; Ebi, Kumiko; Goto, Kazushige","year":2018,"journal":"Nutrients, 10(7)","doi":"10.3390/nu10070893","pmid":"30002346","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03759","title":"A novel peptide dendrimer LTP efficiently facilitates transfection of mammalian cells.","authors":"Kozhikhova, Ksenia V; Andreev, Sergey M; Shilovskiy, Igor P; Timofeeva, Anastasiia V; Gaisina, Alina R; Shatilov, Artem A; Turetskiy, Evgeny A; Andreev, Igor M; Smirnov, Valeriy V; Dvornikov, Anton S; Khaitov, Musa R","year":2018,"journal":"Organic & biomolecular chemistry, 16(43), 8181-8190","doi":"10.1039/c8ob02039f","pmid":"30357248","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03760","title":"Analysis of new growth promoting black market products.","authors":"Krug, Oliver; Thomas, Andreas; Malerød-Fjeld, Helle; Dehnes, Yvette; Laussmann, Tim; Feldmann, Ingo; Sickmann, Albert; Thevis, Mario","year":2018,"journal":"Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society, 41, 1-6","doi":"10.1016/j.ghir.2018.05.001","pmid":"29864719","tags":["anti-doping","growth-hormone","black-market"],"studyType":"Analytical / Forensic Study","evidenceStrength":"Moderate","keyFinding":"Researchers analyzing black market growth-promoting products discovered several previously unknown compounds. They found a modified form of human growth hormone with 192 amino acids instead of the normal 191 — it had an extra alanine added to one end, giving it a slightly different molecular mass (22,195 Da versus the normal 22,124 Da).\n\nThey also identified three novel GHRP analogs: Gly-GHRP-6, Gly-GHRP-2, and Gly-Ipamorelin. Each is a known growth hormone-releasing peptide with an extra glycine residue attached to the N-terminus. The identities of Gly-Ipamorelin and Gly-GHRP-2 were confirmed by synthesizing the peptides from scratch and comparing them. Preliminary in-vitro metabolism experiments were also conducted on these new analogs.","whyItMatters":"The black market for performance-enhancing peptides is constantly evolving. This study reveals that underground manufacturers are creating slightly modified versions of known peptides — likely to evade doping detection tests that look for specific molecular signatures. These designer analogs pose a double threat: they may escape standard drug testing, and their safety profiles are completely unknown since they've never been studied in humans.","specificNumbers":"192-amino acid GH variant (vs normal 191) · mass 22,195 Da (vs 22,124 Da) · 3 novel GHRP analogs identified · Gly-GHRP-6, Gly-GHRP-2, Gly-Ipamorelin","methodology":"The researchers obtained black market products and analyzed them using liquid chromatography coupled with high-resolution, high-accuracy mass spectrometry. They used both top-down approaches (analyzing whole molecules) and bottom-up approaches (breaking molecules into fragments) to characterize the compounds. For two of the novel peptides, they confirmed their structures by custom-synthesizing the peptides and comparing them to the black market samples. In-vitro metabolism experiments provided preliminary data on how these compounds might break down after administration.","limitations":"This study analyzed a limited number of black market products and cannot represent the full scope of what's being sold. The in-vitro metabolism experiments are preliminary and don't capture how these compounds would behave in a living human body. The study identifies the compounds but does not assess their biological activity, potency, or safety. The source and manufacturing conditions of the black market products are unknown."},{"rthcId":"RPEP-03761","title":"Effects of Intranasal Oxytocin Administration on Sexual Functions in Healthy Women: A Laboratory Paradigm.","authors":"Kruger, Tillmann H C; Deiter, Frank; Zhang, Yuanyuan; Jung, Stefanie; Schippert, Cordula; Kahl, Kai G; Heinrichs, Markus; Schedlowski, Manfred; Hartmann, Uwe","year":2018,"journal":"Journal of clinical psychopharmacology, 38(3), 239-242","doi":"10.1097/JCP.0000000000000863","pmid":"29596150","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03762","title":"Efficacy and safety profile of once-weekly dulaglutide in type 2 diabetes: a report on the emerging new data.","authors":"Kugler, Anne J; Thiman, Michael L","year":2018,"journal":"Diabetes, metabolic syndrome and obesity : targets and therapy, 11, 187-197","doi":"10.2147/DMSO.S134960","pmid":"29780260","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Dulaglutide demonstrated robust A1c reduction ranging from -0.78% to -1.64% over 52-104 weeks in head-to-head comparisons, consistently outperforming metformin, insulin glargine, and sitagliptin. As add-on therapy, it provided additional A1c lowering of -1.4% to -1.44% beyond monotherapy with glimepiride or glargine.\n\nDulaglutide also outperformed exenatide when added to metformin plus pioglitazone, and beat glargine when added to metformin plus glimepiride. It was non-inferior to liraglutide when added to metformin. In nearly all AWARD trials, full-dose dulaglutide enabled significantly more patients to reach their A1c goals. Pooled safety data showed no increased risk of pancreatitis or neoplasm.","whyItMatters":"GLP-1 receptor agonists have transformed type 2 diabetes management. This review provided a comprehensive snapshot of dulaglutide's clinical performance at a time when the class was rapidly expanding, helping clinicians understand how this once-weekly option compared to daily alternatives and other diabetes medications in real trial settings.","specificNumbers":"","methodology":"This was a review of published clinical trial data, primarily from the AWARD (Assessment of Weekly AdministRation of LY2189265 in Diabetes) series of trials. The review synthesized results from head-to-head comparisons against multiple standard-of-care agents and examined class-wide meta-analyses for side effect profiles.","limitations":"This is a narrative review, not a systematic review or meta-analysis, so it may not capture all available data. The REWIND cardiovascular outcomes trial had not yet reported at the time of publication. Head-to-head comparisons across different trials are limited by differing patient populations, baseline characteristics, and study designs. Long-term safety data beyond the trial periods reviewed was limited."},{"rthcId":"RPEP-03763","title":"Antibody Epitope of Human α-Galactosidase A Revealed by Affinity Mass Spectrometry: A Basis for Reversing Immunoreactivity in Enzyme Replacement Therapy of Fabry Disease.","authors":"Kukacka, Zdenek; Iurascu, Marius; Lupu, Loredana; Rusche, Hendrik; Murphy, Mary; Altamore, Lorenzo; Borri, Fabio; Maeser, Stefan; Papini, Anna Maria; Hennermann, Julia; Przybylski, Michael","year":2018,"journal":"ChemMedChem, 13(9), 909-915","doi":"10.1002/cmdc.201800094","pmid":"29473701","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03764","title":"Expression of human cathelicidin peptide LL-37 in inflammatory bowel disease.","authors":"Kusaka, S; Nishida, A; Takahashi, K; Bamba, S; Yasui, H; Kawahara, M; Inatomi, O; Sugimoto, M; Andoh, A","year":2018,"journal":"Clinical and experimental immunology, 191(1), 96-106","doi":"10.1111/cei.13047","pmid":"28872665","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03765","title":"Specific Collagen Peptides Improve Bone Mineral Density and Bone Markers in Postmenopausal Women-A Randomized Controlled Study.","authors":"König, Daniel; Oesser, Steffen; Scharla, Stephan; Zdzieblik, Denise; Gollhofer, Albert","year":2018,"journal":"Nutrients, 10(1)","doi":"10.3390/nu10010097","pmid":"29337906","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"After 12 months, the collagen peptide group showed significant increases in bone mineral density compared to placebo at both measurement sites. Spine T-score changed by +0.1 in the collagen group vs. -0.03 in placebo (p=0.030). Femoral neck T-score changed by +0.09 vs. -0.01 (p=0.003). Bone formation marker P1NP increased significantly in the collagen group (p=0.007), while bone degradation marker CTX-1 increased significantly in the placebo group (p=0.011), indicating a favorable shift in the balance between bone formation and resorption.","whyItMatters":"Osteoporosis affects millions of postmenopausal women and leads to fractures that cause significant disability and mortality. If a simple daily collagen peptide supplement can increase bone density and improve bone markers, it could offer an accessible, low-risk complementary approach to osteoporosis prevention alongside calcium, vitamin D, and pharmaceutical treatments.","specificNumbers":"","methodology":"Randomized, placebo-controlled, double-blinded study enrolling 131 postmenopausal women (102 completers, all 131 included in intention-to-treat analysis). Mean age 64.3 years, mean BMI 23.6 kg/m², with T-scores indicating osteopenia. Treatment group received 5 g/day of specific collagen peptides orally for 12 months. Primary endpoints were BMD changes at spine and femoral neck measured by DXA. Secondary endpoints included bone turnover markers P1NP and CTX-1.","limitations":"The study had a 22% dropout rate (131 enrolled, 102 completed), though intention-to-treat analysis was used. One author (Oesser) is associated with a collagen peptide manufacturer, raising potential conflict of interest. The T-score changes, while statistically significant, were modest. The study did not assess fracture risk reduction, which is the clinically meaningful endpoint. A single trial of this size should be replicated before drawing firm conclusions."},{"rthcId":"RPEP-03766","title":"An In vivo study: Adjuvant activity of poly-n-vinyl-2-pyrrolidone-co-acrylic acid on immune responses against Melanoma synthetic peptide.","authors":"Kızılbey, Kadriye; Mansuroğlu, Banu; Derman, Serap; Mustafaeva Akdeste, Zeynep","year":2018,"journal":"Bioengineered, 9(1), 134-143","doi":"10.1080/21655979.2017.1373529","pmid":"28910565","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03767","title":"Substance P represents a novel first-line defense mechanism in the nose.","authors":"Larsson, Olivia; Tengroth, Lotta; Xu, Yuan; Uddman, Rolf; Kumlien Georén, Susanna; Cardell, Lars-Olaf","year":2018,"journal":"The Journal of allergy and clinical immunology, 141(1), 128-136.e3","doi":"10.1016/j.jaci.2017.01.021","pmid":"28219705","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03768","title":"Hydrogenation catalyst generates cyclic peptide stereocentres in sequence.","authors":"Le, Diane N; Hansen, Eric; Khan, Hasan A; Kim, Byoungmoo; Wiest, Olaf; Dong, Vy M","year":2018,"journal":"Nature chemistry, 10(9), 968-973","doi":"10.1038/s41557-018-0089-5","pmid":"30061616","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03769","title":"Effects of Semax on the Default Mode Network of the Brain.","authors":"Lebedeva, I S; Panikratova, Ya R; Sokolov, O Yu; Kupriyanov, D A; Rumshiskaya, A D; Kost, N V; Myasoedov, N F","year":2018,"journal":"Bulletin of experimental biology and medicine, 165(5), 653-656","doi":"10.1007/s10517-018-4234-3","pmid":"30225715","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Intranasal Semax (1%) produced a measurable increase in the volume of the default mode network's rostral subcomponent (medial frontal cortex) compared to placebo, as detected by resting state fMRI. This effect was visible within 5 to 20 minutes of nasal administration. The finding confirms that Semax reaches the brain and alters neural network activity in a specific, topographically defined manner.","whyItMatters":"This is one of the few human neuroimaging studies showing a peptide nootropic producing measurable changes in brain network activity. The default mode network is involved in self-referential thinking, mind-wandering, and memory consolidation. Showing that Semax specifically affects the medial frontal cortex component — associated with social cognition and emotional processing — provides neurobiological evidence for its reported cognitive and mood effects.","specificNumbers":"n=24 (14 Semax, 10 placebo) · 1% intranasal Semax · fMRI at baseline, 5 min, and 20 min · Increased DMN rostral subcomponent volume · Medial frontal cortex affected","methodology":"Placebo-controlled study in 24 healthy volunteers (11 men, 13 women, mean age 43.9 years). Resting state fMRI was performed three times: immediately before, 5 minutes after, and 20 minutes after intranasal administration of 1% Semax (n=14) or placebo (n=10). The default mode network was identified and its subcomponent topography analyzed.","limitations":"Very small sample size (14 Semax vs. 10 placebo) limits statistical power and generalizability. The study only measured network volume changes, not cognitive or behavioral outcomes — so the functional significance of the DMN change is unknown. Only two post-administration time points were measured (5 and 20 minutes), missing later effects. No blinding verification was reported. The study was conducted by researchers associated with Semax's development institute."},{"rthcId":"RPEP-03770","title":"Oleuropein reduces anxiety-like responses by activating of serotonergic and neuropeptide Y (NPY)-ergic systems in a rat model of post-traumatic stress disorder.","authors":"Lee, Bombi; Shim, Insop; Lee, Hyejung; Hahm, Dae-Hyun","year":2018,"journal":"Animal cells and systems, 22(2), 109-117","doi":"10.1080/19768354.2018.1426699","pmid":"30460087","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03771","title":"FRET Reagent Reveals the Intracellular Processing of Peptide-Linked Antibody-Drug Conjugates.","authors":"Lee, Byoung-Chul; Chalouni, Cecile; Doll, Sophia; Nalle, Sam C; Darwish, Martine; Tsai, Siao Ping; Kozak, Katherine R; Del-Rosario, Geoffrey; Yu, Shang-Fan; Erickson, Hans; Vandlen, Richard","year":2018,"journal":"Bioconjugate chemistry, 29(7), 2468-2477","doi":"10.1021/acs.bioconjchem.8b00362","pmid":"29856915","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03772","title":"Activation of Glucagon-Like Peptide-1 Receptor Promotes Neuroprotection in Experimental Autoimmune Encephalomyelitis by Reducing Neuroinflammatory Responses.","authors":"Lee, Chi-Ho; Jeon, Se Jin; Cho, Kyu Suk; Moon, Eunjung; Sapkota, Arjun; Jun, Hee Sook; Ryu, Jong Hoon; Choi, Ji Woong","year":2018,"journal":"Molecular neurobiology, 55(4), 3007-3020","doi":"10.1007/s12035-017-0550-2","pmid":"28456941","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03773","title":"Effect of the Orally Active Growth Hormone Secretagogue MK-677 on Somatic Growth in Rats.","authors":"Lee, Junghun; Kwon, Ahreum; Chae, Hyun Wook; Lee, Woo Jung; Kim, Tae Hyuk; Kim, Ho Seong","year":2018,"journal":"Yonsei medical journal, 59(10), 1174-1180","doi":"10.3349/ymj.2018.59.10.1174","pmid":"30450851","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03774","title":"A facile approach to enhance antigen response for personalized cancer vaccination.","authors":"Li, Aileen Weiwei; Sobral, Miguel C; Badrinath, Soumya; Choi, Youngjin; Graveline, Amanda; Stafford, Alexander G; Weaver, James C; Dellacherie, Maxence O; Shih, Ting-Yu; Ali, Omar A; Kim, Jaeyun; Wucherpfennig, Kai W; Mooney, David J","year":2018,"journal":"Nature materials, 17(6), 528-534","doi":"10.1038/s41563-018-0028-2","pmid":"29507416","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03775","title":"Substance P-regulated leukotriene B4 production promotes acute pancreatitis-associated lung injury through neutrophil reverse migration.","authors":"Li, Bin; Han, Xiao; Ye, Xin; Ni, Jianbo; Wu, Jianghong; Dai, Juanjuan; Wu, Zengkai; Chen, Congying; Wan, Rong; Wang, Xingpeng; Hu, Guoyong","year":2018,"journal":"International immunopharmacology, 57, 147-156","doi":"10.1016/j.intimp.2018.02.017","pmid":"29482159","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In two mouse models of acute pancreatitis (caerulein/LPS and L-arginine), LTB4 and its receptor BLT1 were markedly upregulated. Blocking BLT1 with the antagonist LY293111 achieved three effects: attenuated pancreatitis severity, decreased neutrophil reverse transendothelial migration (rTEM) into the circulation, and alleviated acute lung injury severity.\n\nIn vitro, substance P treatment of pancreatic acinar cells increased LTB4 production through activation of protein kinase Cα (PKCα) and MAP kinases (ERK, p38, JNK). Blocking substance P's neurokinin-1 receptor with CP96345 significantly reduced pancreatitis severity and LTB4 levels. The complete pathway: substance P → NK-1 receptor → PKCα/MAPK → LTB4 production → BLT1 activation → neutrophil reverse migration → lung injury.","whyItMatters":"Acute lung injury is one of the most dangerous complications of severe pancreatitis, contributing significantly to mortality. This study reveals a specific and potentially druggable pathway: substance P drives LTB4-mediated neutrophil reverse migration that damages the lungs. Since both NK-1 receptor antagonists and LTB4 receptor blockers already exist as drugs, this pathway could be targeted to prevent lung damage in pancreatitis patients — a setting where few effective treatments currently exist.","specificNumbers":"","methodology":"Two in vivo acute pancreatitis models were used in BALB/c mice: caerulein plus lipopolysaccharide, and L-arginine. LTB4 levels and BLT1 expression were measured. The BLT1 antagonist LY293111 was used to block leukotriene signaling. Neutrophil reverse transendothelial migration was assessed. In vitro, pancreatic acinar cells were treated with substance P and analyzed for LTB4 production and PKCα/MAPK phosphorylation. The NK-1 receptor antagonist CP96345 was tested for its ability to reduce pancreatitis severity and LTB4 levels.","limitations":"All experiments were conducted in mice, and the pancreatitis models (caerulein/LPS and L-arginine) are standardized but do not perfectly replicate the most common human cause — gallstone pancreatitis. The in vitro work used isolated pancreatic acinar cells, removing the complex multicellular environment of the pancreas. Specific quantitative measures of disease severity reduction are not detailed in the abstract. The study focused on acute effects; whether blocking this pathway remains effective in more severe or prolonged pancreatitis is unknown."},{"rthcId":"RPEP-03776","title":"Blocking constitutive activity of GHSR1a in the lateral amygdala facilitates acquisition of conditioned taste aversion.","authors":"Li, Nan; Song, Ge; Wang, Yaohui; Zhu, Qianqian; Han, Fubing; Zhang, Chonghui; Zhou, Yu","year":2018,"journal":"Neuropeptides, 68, 22-27","doi":"10.1016/j.npep.2017.12.001","pmid":"29254662","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03777","title":"Elevated endogenous opioids in obstructive jaundice: The possible skin mechanisms.","authors":"Li, Xiaoqian; Zhu, Jiao; Tao, Yong; Tao, Kunming","year":2018,"journal":"Medical hypotheses, 116, 119-121","doi":"10.1016/j.mehy.2018.05.013","pmid":"29857894","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03778","title":"Inhibitory effect of timolol on topical glucocorticoid‑induced skin telangiectasia.","authors":"Li, Yan-Fei; Chen, Xiao-Yan; Lei, Tie-Chi","year":2018,"journal":"Molecular medicine reports, 18(3), 2823-2831","doi":"10.3892/mmr.2018.9266","pmid":"30015958","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In the rabbit model, erythema, papules, and telangiectasia were significantly diminished after 4 weeks of timolol treatment. The antimicrobial peptide LL-37 and the enzyme KLK5 were elevated in steroid-damaged skin but decreased after timolol treatment.\n\nIn human patients with facial telangiectasia, cheeks treated with timolol plus tacrolimus showed markedly reduced telangiectasia compared to tacrolimus alone by week 4. Both groups showed reduced erythema by week 1, but the timolol combination was significantly superior for visible blood vessels. Color measurements confirmed significant differences in L (lightness) and a (redness) values between treatment and control cheeks (p<0.05).","whyItMatters":"Facial corticosteroid addiction dermatitis is a growing problem, particularly in regions where potent steroid creams are used long-term or inappropriately. The visible blood vessels are disfiguring and difficult to treat. This study identifies a new mechanistic pathway — abnormal LL-37 expression — and offers a simple, accessible treatment option using timolol, an inexpensive and widely available medication. The split-face design in humans provides particularly compelling evidence since each patient serves as their own control.","specificNumbers":"","methodology":"The study had two parts. First, rabbit ears were treated with flumethasone ointment to induce telangiectasia, then treated with 0.5% timolol eye drops twice daily for 4 weeks. LL-37 and KLK5 expression was measured by PCR. Second, human patients with facial telangiectasia served as their own controls — one cheek received timolol plus tacrolimus ointment, the other received tacrolimus alone for 8 weeks. Changes were tracked by dermoscopy and chromameter color measurements at weeks 1, 2, 4, and 8.","limitations":"The human portion of the study did not specify the number of patients enrolled. The split-face design, while controlling for individual variation, only compared timolol+tacrolimus versus tacrolimus alone — there was no timolol-only or placebo arm. The 8-week follow-up is relatively short for a chronic condition. The rabbit model may not perfectly replicate human steroid-induced skin changes. The mechanism linking KLK5 to LL-37 in this context needs further investigation."},{"rthcId":"RPEP-03779","title":"Egg Protein-Derived Bioactive Peptides: Preparation, Efficacy, and Absorption.","authors":"Liao, Wang; Jahandideh, Forough; Fan, Hongbing; Son, Myoungjin; Wu, Jianping","year":2018,"journal":"Advances in food and nutrition research, 85, 1-58","doi":"10.1016/bs.afnr.2018.02.001","pmid":"29860972","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03780","title":"Purification and Characterization of Peptides Inhibiting MMP-1 Activity with C Terminate of Gly-Leu from Simulated Gastrointestinal Digestion Hydrolysates of Tilapia (Oreochromis niloticus) Skin Gelatin.","authors":"Liping, Sun; Qiuming, Liu; Jian, Fan; Xiao, Li; Yongliang, Zhuang","year":2018,"journal":"Journal of agricultural and food chemistry, 66(3), 593-601","doi":"10.1021/acs.jafc.7b04196","pmid":"29272917","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03781","title":"Choices for long-term hypertensive control in patients after first-ever hemorrhagic stroke: a nationwide cohort study.","authors":"Liu, Chi-Hung; Lin, Yu-Sheng; Chi, Ching-Chi; Liou, Chia-Wei; Lee, Jiann-Der; Peng, Tsung-I; Lee, Tsong-Hai","year":2018,"journal":"Therapeutic advances in neurological disorders, 11, 1756286418802688","doi":"10.1177/1756286418802688","pmid":"30283500","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03782","title":"Synergy effects of Polyinosinic-polycytidylic acid, CpG oligodeoxynucleotide, and cationic peptides to adjuvant HPV E7 epitope vaccine through preventive and therapeutic immunization in a TC-1 grafted mouse model.","authors":"Liu, Cunbao; Chu, Xiaojie; Sun, Pengyan; Feng, Xuejun; Huang, Weiwei; Liu, Hongxian; Ma, Yanbing","year":2018,"journal":"Human vaccines & immunotherapeutics, 14(4), 931-940","doi":"10.1080/21645515.2017.1420446","pmid":"29271696","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03783","title":"Serine/Threonine Ligation: Origin, Mechanistic Aspects, and Applications.","authors":"Liu, Han; Li, Xuechen","year":2018,"journal":"Accounts of chemical research, 51(7), 1643-1655","doi":"10.1021/acs.accounts.8b00151","pmid":"29979577","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03784","title":"Synthesis and semisynthesis of selenopeptides and selenoproteins.","authors":"Liu, Jun; Cheng, Rujin; Rozovsky, Sharon","year":2018,"journal":"Current opinion in chemical biology, 46, 41-47","doi":"10.1016/j.cbpa.2018.04.008","pmid":"29723718","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03785","title":"EGFR-targeting, β-defensin-tailored fusion protein exhibits high therapeutic efficacy against EGFR-expressed human carcinoma via mitochondria-mediated apoptosis.","authors":"Liu, Wen-Juan; Liu, Xiu-Jun; Xu, Jian; Li, Liang; Li, Yi; Zhang, Sheng-Hua; Wang, Jia-Lin; Miao, Qing-Fang; Zhen, Yong-Su","year":2018,"journal":"Acta pharmacologica Sinica, 39(11), 1777-1786","doi":"10.1038/s41401-018-0069-8","pmid":"30013033","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03786","title":"Postmenopausal osteoporosis is associated with the regulation of SP, CGRP, VIP, and NPY.","authors":"Liu, Xiaoguang; Liu, Hengrui; Xiong, Yingquan; Yang, Li; Wang, Chaopeng; Zhang, Ronghua; Zhu, Xiaofeng","year":2018,"journal":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 104, 742-750","doi":"10.1016/j.biopha.2018.04.044","pmid":"29807224","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03787","title":"Bioactive peptides derived from egg proteins: A review.","authors":"Liu, Ya-Fei; Oey, Indrawati; Bremer, Phil; Carne, Alan; Silcock, Pat","year":2018,"journal":"Critical reviews in food science and nutrition, 58(15), 2508-2530","doi":"10.1080/10408398.2017.1329704","pmid":"28609123","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03788","title":"No pancreatic safety concern following glucagon-like peptide-1 receptor agonist therapies: A pooled analysis of cardiovascular outcome trials.","authors":"Liu, Ye; Tian, Qing; Yang, Jin; Wang, Haining; Hong, Tianpei","year":2018,"journal":"Diabetes/metabolism research and reviews, 34(8), e3061","doi":"10.1002/dmrr.3061","pmid":"30109766","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03789","title":"Hypochlorite modified albumins promote cell death in the tubule interstitium in rats via mitochondrial damage in obstructive nephropathy and the protective effects of antioxidant peptides.","authors":"Liu, Zong-Rui; Chen, Si-Qi; Zou, Yao-Wei; Wu, Xiao-Yu; Li, Hong-Ying; Wang, Xiao-Qiao; Shi, Yue; Niu, Hong-Xin","year":2018,"journal":"Free radical research, 52(5), 616-628","doi":"10.1080/10715762.2018.1457789","pmid":"29781318","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03790","title":"Insulin and glucose-lowering agents for treating people with diabetes and chronic kidney disease.","authors":"Lo, Clement; Toyama, Tadashi; Wang, Ying; Lin, Jin; Hirakawa, Yoichiro; Jun, Min; Cass, Alan; Hawley, Carmel M; Pilmore, Helen; Badve, Sunil V; Perkovic, Vlado; Zoungas, Sophia","year":2018,"journal":"The Cochrane database of systematic reviews, 9(9), CD011798","doi":"10.1002/14651858.CD011798.pub2","pmid":"30246878","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03791","title":"Effects of lysine-to-arginine substitution on antimicrobial activity of cationic stapled heptapeptides.","authors":"Luong, Huy X; Kim, Do-Hee; Lee, Bong-Jin; Kim, Young-Woo","year":2018,"journal":"Archives of pharmacal research, 41(11), 1092-1097","doi":"10.1007/s12272-018-1084-5","pmid":"30361948","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Lysine-to-arginine substitution in hydrocarbon-stapled antimicrobial heptapeptides produced variable effects on antimicrobial potency and selectivity. The outcomes depended on the number of substitutions and the positions substituted within the helical scaffold.\n\nThe results challenge the common assumption that arginine universally enhances AMP activity. In this stapled peptide scaffold, antimicrobial potency and selectivity were influenced by a complex interplay of structural and chemical changes accompanying the substitution, rather than simply the type of cationic residue. The study demonstrates that design rules from natural AMPs don't always transfer to engineered scaffolds.","whyItMatters":"Peptide antibiotic design relies on structure-activity rules, many derived from studying natural AMPs. This study shows those rules don't always apply to engineered stapled peptides. Understanding when common design assumptions break down is essential for efficiently developing the next generation of peptide antibiotics — preventing wasted effort on modifications that don't work in specific scaffolds.","specificNumbers":"","methodology":"The researchers synthesized a series of stapled heptapeptide variants with systematic lysine-to-arginine substitutions at different positions. They tested antimicrobial activity against gram-positive and gram-negative bacteria using microbial sensitivity tests, evaluated hemolytic activity against human red blood cells, and analyzed structural properties of the peptides.","limitations":"The study examined a single stapled heptapeptide scaffold, so findings may not generalize to other stapled or non-stapled AMP designs. Only three lysine positions were tested, limiting the combinatorial space explored. In vivo activity and pharmacokinetics were not assessed. The hemolytic assay provides a safety indicator but doesn't capture all aspects of mammalian cell toxicity."},{"rthcId":"RPEP-03792","title":"Advances in macrocyclic peptide-based antibiotics.","authors":"Luther, Anatol; Bisang, Christian; Obrecht, Daniel","year":2018,"journal":"Bioorganic & medicinal chemistry, 26(10), 2850-2858","doi":"10.1016/j.bmc.2017.08.006","pmid":"28886999","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03793","title":"Mechanisms underlying the rapid-acting antidepressant-like effects of neuropeptide VGF (non-acronymic) C-terminal peptide TLQP-62.","authors":"Lv, Dan; Chen, Yaping; Shen, Mengxin; Liu, Xu; Zhang, Yanhua; Xu, Jiangping; Wang, Chuang","year":2018,"journal":"Neuropharmacology, 143, 317-326","doi":"10.1016/j.neuropharm.2018.09.046","pmid":"30291938","tags":["neuroscience-and-neuropeptides"],"studyType":"animal-study","evidenceStrength":"low","keyFinding":"The neuropeptide fragment TLQP-62, derived from the VGF protein, produced rapid antidepressant-like effects when administered directly into the prefrontal cortex of mice. It also reversed depression-like behaviors caused by chronic social defeat stress — a validated mouse model of depression.\n\nThe mechanism was traced to a specific signaling cascade: TLQP-62 activates the TrkB receptor (the BDNF receptor), which triggers mTOR signaling, decreases the gene BICC1, and increases synaptic proteins including the AMPA receptor GluA1 subunit. When researchers blocked TrkB with the antagonist ANA-12, all of TLQP-62's antidepressant effects were abolished — confirming TrkB as the essential starting point of the cascade.","whyItMatters":"Most antidepressants take weeks to work. TLQP-62 produces rapid antidepressant effects through a pathway that overlaps with ketamine's mechanism (TrkB/mTOR/synaptic protein synthesis). This suggests VGF-derived peptides could represent a new class of fast-acting antidepressants that work through the brain's own neurotrophic system rather than targeting serotonin or other monoamines.","specificNumbers":"TLQP-62 infused into PFC · Rapid antidepressant effects · Reversed CSDS-induced depression · TrkB/mTOR/BICC1 signaling pathway · GluA1 phosphorylation at Ser845 · Effects abolished by TrkB antagonist ANA-12","methodology":"Mouse study using two depression models: acute behavioral tests and chronic social defeat stress (CSDS). TLQP-62 was administered directly into the prefrontal cortex. Researchers measured behavioral outcomes, signaling proteins (TrkB, mTOR, BICC1, GluA1), and phosphorylation states. The TrkB antagonist ANA-12 was used to confirm mechanism specificity.","limitations":"Animal study only — no human data. TLQP-62 was delivered directly into the brain, which isn't a viable clinical route. The peptide's ability to cross the blood-brain barrier from systemic administration is unknown. Male mice only. The chronic social defeat stress model, while validated, doesn't fully capture human depression."},{"rthcId":"RPEP-03794","title":"High Throughput Screening for Natural Host Defense Peptide-Inducing Compounds as Novel Alternatives to Antibiotics.","authors":"Lyu, Wentao; Deng, Zhuo; Sunkara, Lakshmi T; Becker, Sage; Robinson, Kelsy; Matts, Robert; Zhang, Guolong","year":2018,"journal":"Frontiers in cellular and infection microbiology, 8, 191","doi":"10.3389/fcimb.2018.00191","pmid":"29942796","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"From a library of 584 natural products screened using a luciferase reporter system driven by the avian β-defensin 9 (AvBD9) promoter, 21 compounds with a minimum Z-score of 2.0 were identified as defensin inducers.\n\nSecondary screening in chicken macrophages and jejunal (gut) tissue explants confirmed most compounds induced defensin expression dose-dependently. The lead compound wortmannin, when given orally to chickens, enhanced AvBD9 gene expression in the duodenum and also induced most other chicken host defense peptide genes. Wortmannin synergized with butyrate to further amplify defensin production, and this combination significantly augmented the antibacterial activity of chicken monocytes.","whyItMatters":"Antibiotic resistance is one of the greatest threats to global health, and poultry production is a major contributor to antibiotic overuse. Rather than developing new antibiotics that bacteria can evolve resistance to, this approach boosts the animal's own immune defense peptides — a strategy that is inherently harder for bacteria to evade because defensins attack through multiple mechanisms simultaneously. If this approach translates to practice, it could reduce antibiotic use in agriculture while maintaining animal health.","specificNumbers":"","methodology":"Researchers constructed a stable macrophage cell line expressing a luciferase reporter driven by a 2-kb AvBD9 gene promoter using lentiviral transduction and puromycin selection. This reporter line was used for high-throughput screening of 584 natural products, with hits defined as compounds achieving a Z-score ≥ 2.0. Validated hits underwent secondary screening in chicken HTC macrophages and jejunal explants for dose-dependent defensin induction. The lead compound wortmannin was tested in vivo via oral administration to chickens, measuring defensin gene expression in gut tissue. Synergy experiments combined wortmannin with butyrate, and antibacterial activity was assessed using chicken monocyte killing assays.","limitations":"The study was conducted primarily in chicken systems (macrophage cell lines, gut explants, and live chickens), and results may not directly translate to human defensin biology. Wortmannin is a known PI3K inhibitor with multiple cellular effects, which could cause unintended side effects at therapeutic doses. The in vivo validation used oral administration but did not assess disease protection outcomes or safety in long-term feeding trials. The screen focused on defensin induction and did not evaluate whether the induced peptides effectively prevented actual infections in treated animals."},{"rthcId":"RPEP-03795","title":"Human keratinocyte cultures (HaCaT) can be infected by DENV, triggering innate immune responses that include IFNλ and LL37.","authors":"López-González, Moisés; Meza-Sánchez, David; García-Cordero, Julio; Bustos-Arriaga, José; Vélez-Del Valle, Cristina; Marsch-Moreno, Meytha; Castro-Jiménez, Tannya; Flores-Romo, Leopoldo; Santos-Argumedo, Leopoldo; Gutiérrez-Castañeda, Benito; Cedillo-Barrón, Leticia","year":2018,"journal":"Immunobiology, 223(11), 608-617","doi":"10.1016/j.imbio.2018.07.006","pmid":"30007822","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03796","title":"Substance P Antagonist Aprepitant Shows no Additive Effect Compared with Standardized Topical Treatment Alone in Patients with Atopic Dermatitis.","authors":"Lönndahl, Louise; Holst, Mikael; Bradley, Maria; Killasli, Hassan; Heilborn, Johan; Hall, Martin A; Theodorsson, Elvar; Holmberg, Jadwiga; Nordlind, Klas","year":2018,"journal":"Acta dermato-venereologica, 98(3), 324-328","doi":"10.2340/00015555-2852","pmid":"29182791","tags":[],"studyType":"randomized controlled trial","evidenceStrength":"moderate","keyFinding":"Adding the substance P antagonist aprepitant (80 mg/day for 7 days) to standard topical treatment provided no additional benefit over topical treatment alone in adults with moderate-to-severe atopic dermatitis. Both the aprepitant group (n=19) and the control group (n=20) showed improvements in disease severity (SCORAD), itch (pruritus), and scratching movements, but aprepitant did not enhance these improvements. This negative result suggests that blocking substance P via the NK-1 receptor does not meaningfully reduce eczema symptoms beyond what standard topical therapy achieves.","whyItMatters":"Substance P is a neuropeptide involved in itch signaling, inflammation, and the stress response in the skin. Because atopic dermatitis involves intense itching and can worsen with stress, blocking substance P seemed like a rational therapeutic approach. This study's negative result is important because it helps redirect research away from NK-1 receptor antagonism as a standalone strategy for eczema and toward other mechanisms that may be more effective for treating the itch-scratch cycle.","specificNumbers":"n=39 (19 aprepitant, 20 control) · 80 mg/day aprepitant for 7 days · No significant difference in SCORAD, pruritus, or scratching between groups","methodology":"This open randomized trial assigned 39 adults with moderate-to-severe atopic dermatitis to either aprepitant (80 mg/day orally for 7 days) plus standardized topical treatment (moderately strong steroid and moisturizer) or topical treatment alone. Outcomes included SCORAD (a validated disease severity score), pruritus intensity, and objectively measured scratching movements.","limitations":"The study was open-label (not blinded), which could introduce bias in subjective outcome assessments like itch severity. The sample size of 39 is small and may have been underpowered to detect modest effects. The 7-day treatment duration is very short — substance P blockade may require longer treatment to show effects. The dose of 80 mg/day was chosen based on anti-emetic use and may not be optimal for dermatological applications."},{"rthcId":"RPEP-03797","title":"Serum concentrations of antimicrobial peptide cathelicidin LL-37 in patients with bacterial lung infections.","authors":"Majewski, Karol; Kozłowska, Elżbieta; Żelechowska, Paulina; Brzezińska-Błaszczyk, Ewa","year":2018,"journal":"Central-European journal of immunology, 43(4), 453-457","doi":"10.5114/ceji.2018.81355","pmid":"30799994","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03798","title":"Application of Neurokinin-1 Receptor in Targeted Strategies for Glioma Treatment. Part I: Synthesis and Evaluation of Substance P Fragments Labeled with 99mTc and 177Lu as Potential Receptor Radiopharmaceuticals.","authors":"Majkowska-Pilip, Agnieszka; Koźmiński, Przemysław; Wawrzynowska, Anna; Budlewski, Tadeusz; Kostkiewicz, Bogusław; Gniazdowska, Ewa","year":2018,"journal":"Molecules (Basel, Switzerland), 23(10)","doi":"10.3390/molecules23102542","pmid":"30301182","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03799","title":"In vitro evaluation of 225 Ac-DOTA-substance P for targeted alpha therapy of glioblastoma multiforme.","authors":"Majkowska-Pilip, Agnieszka; Rius, Maria; Bruchertseifer, Frank; Apostolidis, Christos; Weis, Mirjam; Bonelli, Milton; Laurenza, Marta; Królicki, Leszek; Morgenstern, Alfred","year":2018,"journal":"Chemical biology & drug design, 92(1), 1344-1356","doi":"10.1111/cbdd.13199","pmid":"29611298","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03800","title":"Potential mechanism of thymosin-α1-membrane interactions leading to pleiotropy: experimental evidence and hypotheses.","authors":"Mandaliti, Walter; Nepravishta, Ridvan; Pica, Francesca; Vallebona, Paola Sinibaldi; Garaci, Enrico; Paci, Maurizio","year":2018,"journal":"Expert opinion on biological therapy, 18(sup1), 33-42","doi":"10.1080/14712598.2018.1456527","pmid":"30063856","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03801","title":"Cardiovascular Safety of Antihyperglycemic Agents: \"Do Good or Do No Harm\".","authors":"Manolis, Antonis A; Manolis, Theodora A; Manolis, Antonis S","year":2018,"journal":"Drugs, 78(15), 1567-1592","doi":"10.1007/s40265-018-0985-4","pmid":"30251174","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03802","title":"Antimicrobial and Chemotactic Activity of Scorpion-Derived Peptide, ToAP2, against Mycobacterium massiliensis.","authors":"Marques-Neto, Lázaro M; Trentini, Monalisa M; das Neves, Rogério C; Resende, Danilo P; Procopio, Victor O; da Costa, Adeliane C; Kipnis, André; Mortari, Márcia R; Schwartz, Elisabeth F; Junqueira-Kipnis, Ana Paula","year":2018,"journal":"Toxins, 10(6)","doi":"10.3390/toxins10060219","pmid":"29848960","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"ToAP2, a peptide from the scorpion Tityus obscurus, inhibited growth of four M. massiliense strains at a minimum bactericidal concentration of 200 µM. At this concentration, it inhibited 50% of bacterial growth in infected macrophages. In mice, ToAP2 reduced bacterial loads in liver, lung, and spleen by approximately 90%, matching clarithromycin effectiveness. Uniquely, ToAP2 also demonstrated chemotactic activity — recruiting monocytes (F4/80low Gr1), neutrophils (F4/80- Gr1), and eosinophils (F4/80+ Gr1+) — and modulated macrophage populations in infected mice, suggesting its in vivo efficacy is enhanced by immune cell recruitment beyond its direct antimicrobial action.","whyItMatters":"Multidrug-resistant mycobacterial infections are notoriously difficult to treat, and the antibiotic pipeline for these pathogens is thin. ToAP2 offers a dual mechanism — direct bacterial killing plus immune system activation — that could make it harder for bacteria to develop resistance. This dual action is particularly valuable against intracellular pathogens like mycobacteria that hide inside immune cells.","specificNumbers":"","methodology":"The researchers performed bioinformatics analysis of ToAP2's structure, then tested it in vitro against four M. massiliense strains to determine minimum bactericidal concentrations. They assessed its ability to kill bacteria inside infected macrophages. In vivo experiments used BALB/c and knockout mice infected with M. massiliense, with ToAP2 treatment compared to clarithromycin. Immune cell recruitment was measured using flow cytometry.","limitations":"This is a preclinical study using mouse models, which may not directly translate to human infections. The minimum bactericidal concentration of 200 µM is relatively high, which could present dosing challenges in clinical applications. Toxicity to human cells was not comprehensively assessed. The study used a limited number of M. massiliense strains."},{"rthcId":"RPEP-03803","title":"Biophysical Investigations Elucidating the Mechanisms of Action of Antimicrobial Peptides and Their Synergism.","authors":"Marquette, Arnaud; Bechinger, Burkhard","year":2018,"journal":"Biomolecules, 8(2)","doi":"10.3390/biom8020018","pmid":"29670065","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Cationic amphipathic antimicrobial peptides align parallel to the bacterial membrane surface, with their polar and non-polar sides mirroring the membrane interface. At low concentrations this causes transient membrane openings; at higher concentrations it leads to complete membrane disintegration. The SMART model captures this range of behaviors.\n\nNew biophysical data (isothermal titration calorimetry, circular dichroism, and dynamic light scattering) revealed that magainin 2 and PGLa together mediate liposome agglutination — causing membrane vesicles to clump together — suggesting a previously unrecognized mechanism behind their well-known synergistic antimicrobial action.","whyItMatters":"With antibiotic resistance rising globally, antimicrobial peptides are being explored as alternatives to conventional antibiotics. Understanding exactly how these peptides physically destroy bacterial membranes — and how combining them amplifies the effect — is essential for developing them as therapeutics. The synergy findings are particularly valuable because synergistic combinations could work at lower individual doses, reducing potential toxicity.","specificNumbers":"","methodology":"This is a review incorporating published and unpublished biophysical data. Techniques include solid-state NMR, molecular dynamics simulations, microscopic imaging of bacterial cells, and new experiments using isothermal titration calorimetry (ITC), circular dichroism (CD), and dynamic light scattering (DLS) to study peptide-membrane and peptide-peptide interactions in model lipid systems.","limitations":"Most experiments were conducted with model lipid membranes (liposomes) rather than intact bacterial cells, which have more complex membrane compositions. The SMART model is descriptive rather than predictive. The synergy mechanisms demonstrated in vitro would need validation in bacterial killing assays and animal models. The review focuses primarily on cationic linear peptides and may not generalize to all antimicrobial peptide classes."},{"rthcId":"RPEP-03804","title":"Growth hormone secretagogue receptor constitutive activity impairs voltage-gated calcium channel-dependent inhibitory neurotransmission in hippocampal neurons.","authors":"Martínez Damonte, Valentina; Rodríguez, Silvia Susana; Raingo, Jesica","year":2018,"journal":"The Journal of physiology, 596(22), 5415-5428","doi":"10.1113/JP276256","pmid":"30199095","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03805","title":"Phase 2 trial of a multivalent WT1 peptide vaccine (galinpepimut-S) in acute myeloid leukemia.","authors":"Maslak, Peter G; Dao, Tao; Bernal, Yvette; Chanel, Suzanne M; Zhang, Rong; Frattini, Mark; Rosenblat, Todd; Jurcic, Joseph G; Brentjens, Renier J; Arcila, Maria E; Rampal, Raajit; Park, Jae H; Douer, Dan; Katz, Laura; Sarlis, Nicholas; Tallman, Martin S; Scheinberg, David A","year":2018,"journal":"Blood advances, 2(3), 224-234","doi":"10.1182/bloodadvances.2017014175","pmid":"29386195","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03806","title":"Neuropeptide Signaling Networks and Brain Circuit Plasticity.","authors":"McClard, Cynthia K; Arenkiel, Benjamin R","year":2018,"journal":"Journal of experimental neuroscience, 12, 1179069518779207","doi":"10.1177/1179069518779207","pmid":"29899664","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03807","title":"β-Defensins: Farming the Microbiome for Homeostasis and Health.","authors":"Meade, Kieran G; O'Farrelly, Cliona","year":2018,"journal":"Frontiers in immunology, 9, 3072","doi":"10.3389/fimmu.2018.03072","pmid":"30761155","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Beta-defensins are multifunctional cationic peptides that manage host-microbe cross-talk across all mucosal systems (oral, respiratory, reproductive, enteric). They act as 'farmers' rather than simply 'killers' — curating microbial diversity to maintain homeostasis rather than eliminating microbes indiscriminately.\n\nSome species show expansions in beta-defensin gene numbers, the functional significance of which is only recently appreciated. Beta-defensin expression is documented before birth, and disruptions in their regulation may contribute to maladaptive neonatal immune programming and subsequent disease susceptibility. The review also presents evidence that beta-defensins serve as sensors of homeostasis and immune vanguards at immunologically privileged sites.","whyItMatters":"As medicine shifts from antibiotic-based microbial clearance to microbiome-aware approaches, understanding how the body naturally manages its microbial communities becomes essential. Beta-defensins represent the body's own selective antimicrobial system — one that's been refined over millions of years of evolution. Harnessing their biology could lead to treatments that fight infections without destroying beneficial microbiomes, addressing a critical limitation of current antibiotics.","specificNumbers":"","methodology":"Narrative review synthesizing recent evidence on beta-defensin biology, focusing on their roles in microbiome management, mucosal immunity, host-microbe interactions, gene family evolution, and neonatal immune programming.","limitations":"This is a narrative review that synthesizes existing evidence without systematic methodology. Much of the evidence for beta-defensin microbiome management comes from animal studies, particularly cattle (the senior author's area). Mechanistic details of how beta-defensins selectively shape microbial communities are still being elucidated. The clinical translation of defensin biology into therapeutic applications remains largely theoretical."},{"rthcId":"RPEP-03808","title":"Mitochondrial-Derived Peptides Exacerbate Senescence.","authors":"Mendelsohn, Andrew R; Larrick, James W","year":2018,"journal":"Rejuvenation research, 21(4), 369-373","doi":"10.1089/rej.2018.2114","pmid":"30058454","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03809","title":"Gut Microbiota-Stimulated Innate Lymphoid Cells Support β-Defensin 14 Expression in Pancreatic Endocrine Cells, Preventing Autoimmune Diabetes.","authors":"Miani, Michela; Le Naour, Julie; Waeckel-Enée, Emmanuelle; Verma, Subash Chand; Straube, Marjolène; Emond, Patrick; Ryffel, Bernhard; van Endert, Peter; Sokol, Harry; Diana, Julien","year":2018,"journal":"Cell metabolism, 28(4), 557-572.e6","doi":"10.1016/j.cmet.2018.06.012","pmid":"30017352","tags":["defensins","autoimmune-diabetes","microbiome"],"studyType":"Animal Study","evidenceStrength":"Preliminary","keyFinding":"Gut microbiota stimulate innate lymphoid cells (ILCs) that travel to the pancreas and trigger pancreatic endocrine cells to produce a defensin peptide called mouse β-defensin 14 (mBD14). This defensin then activates a protective immune cascade: it signals through Toll-like receptor 2 to stimulate IL-4-secreting B cells, which activate regulatory macrophages, which in turn generate regulatory T cells that prevent autoimmune attack on insulin-producing cells.\n\nThe gut microbiota drives this process by producing aryl hydrocarbon receptor (AHR) ligands and butyrate, which promote IL-22 secretion by pancreatic ILCs. In non-obese diabetic (NOD) mice — a model for type 1 diabetes — both a dysbiotic microbiome and a low-affinity AHR gene variant explain why this protective defensin pathway fails, leading to diabetes development.","whyItMatters":"Type 1 diabetes results from the immune system destroying insulin-producing pancreatic beta cells, and there is no cure. This study reveals a completely new mechanism by which gut bacteria protect the pancreas from autoimmune attack — through a defensin peptide that orchestrates an anti-inflammatory immune response. This connects three major research areas: the microbiome, antimicrobial peptides, and autoimmune diabetes. If this pathway also exists in humans, it could open new therapeutic approaches to preventing type 1 diabetes.","specificNumbers":"β-defensin 14 · TLR2 signaling · IL-22 from ILCs · AHR ligands + butyrate from gut bacteria · NOD mouse model","methodology":"The researchers used non-obese diabetic (NOD) mice as a model for type 1 diabetes. They investigated the interaction between gut microbiota, innate lymphoid cells, and pancreatic endocrine cells using a combination of techniques including analysis of defensin expression, immune cell profiling, microbiota manipulation, and metabolite analysis. They mapped the signaling cascade from gut-derived molecules (AHR ligands, butyrate) through IL-22-producing ILCs to defensin expression and downstream immune regulation.","limitations":"This is an animal study using NOD mice, which are a model for type 1 diabetes but do not perfectly replicate the human disease. The specific defensin studied (mBD14) is a mouse defensin — the human equivalent may behave differently. Translation of these findings to human type 1 diabetes prevention would require extensive further research. The complexity of the signaling cascade makes therapeutic targeting challenging."},{"rthcId":"RPEP-03810","title":"Amylin in Alzheimer's disease: Pathological peptide or potential treatment?","authors":"Mietlicki-Baase, Elizabeth G","year":2018,"journal":"Neuropharmacology, 136(Pt B), 287-297","doi":"10.1016/j.neuropharm.2017.12.016","pmid":"29233636","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies a key paradox in amylin research for Alzheimer's disease. Multiple studies demonstrate that amylin and the amylin analog pramlintide (already FDA-approved for diabetes) can reduce amyloid burden in the brain and improve cognitive symptoms in Alzheimer's models.\n\nHowever, contradictory evidence shows that amylin has a propensity to misfold and aggregate under certain conditions — similar to the amyloid-beta protein central to Alzheimer's pathology. This raises the possibility that amylin could contribute to, rather than treat, Alzheimer's disease. The author identifies several critical gaps including limited understanding of amylin system changes during aging, complexities of amylin receptor signaling, and how changing pathophysiology during AD progression might explain these conflicting results.","whyItMatters":"Alzheimer's disease affects over 50 million people worldwide and currently has no cure. The possibility that pramlintide — an already FDA-approved drug — could be repurposed for Alzheimer's treatment is exciting because it would bypass years of drug development. However, the conflicting evidence about amylin's role means we need to understand whether this peptide helps or harms before pursuing it as a treatment. Getting this wrong could potentially worsen the disease in patients.","specificNumbers":"","methodology":"This is a narrative review of the published literature examining both the beneficial and harmful roles of amylin in Alzheimer's disease. The author systematically evaluates preclinical and clinical evidence from both perspectives and identifies methodological factors and knowledge gaps that may explain contradictory findings in the field.","limitations":"As a narrative review, the paper reflects the author's interpretation and selection of the literature rather than a systematic analysis. The conflicting evidence in the field itself is a major limitation — the same peptide showing both beneficial and harmful effects makes it difficult to draw definitive conclusions. Most evidence comes from animal models, with limited human clinical data on amylin's effects in Alzheimer's patients."},{"rthcId":"RPEP-03811","title":"Maternal Deprivation Increases Anxiety- and Depressive-Like Behaviors in an Age-Dependent Fashion and Reduces Neuropeptide Y Expression in the Amygdala and Hippocampus of Male and Female Young Adult Rats.","authors":"Miragaia, Alexandra S; de Oliveira Wertheimer, Guilherme S; Consoli, Amanda C; Cabbia, Rafael; Longo, Beatriz M; Girardi, Carlos E N; Suchecki, Deborah","year":2018,"journal":"Frontiers in behavioral neuroscience, 12, 159","doi":"10.3389/fnbeh.2018.00159","pmid":"30131681","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03812","title":"Barley β-glucan improves metabolic condition via short-chain fatty acids produced by gut microbial fermentation in high fat diet fed mice.","authors":"Miyamoto, Junki; Watanabe, Keita; Taira, Satsuki; Kasubuchi, Mayu; Li, Xuan; Irie, Junichiro; Itoh, Hiroshi; Kimura, Ikuo","year":2018,"journal":"PloS one, 13(4), e0196579","doi":"10.1371/journal.pone.0196579","pmid":"29698465","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03813","title":"Acylation of the S413-PV cell-penetrating peptide as a means of enhancing its capacity to mediate nucleic acid delivery: Relevance of peptide/lipid interactions.","authors":"Morais, Catarina M; Cardoso, Ana M; Cunha, Pedro P; Aguiar, Luísa; Vale, Nuno; Lage, Emílio; Pinheiro, Marina; Nunes, Cláudia; Gomes, Paula; Reis, Salette; Castro, M Margarida C A; Pedroso de Lima, Maria C; Jurado, Amália S","year":2018,"journal":"Biochimica et biophysica acta. Biomembranes, 1860(12), 2619-2634","doi":"10.1016/j.bbamem.2018.10.002","pmid":"30291923","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03814","title":"High molecular weight hyaluronic acid: a two-pronged protectant against infection of the urogenital tract?","authors":"Mowbray, Catherine A; Shams, Syema; Chung, Git; Stanton, Anna; Aldridge, Phillip; Suchenko, Andrejus; Pickard, Robert S; Ali, Ased Sm; Hall, Judith","year":2018,"journal":"Clinical & translational immunology, 7(6), e1021","doi":"10.1002/cti2.1021","pmid":"29928502","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03815","title":"Nrp-1 receptor targeting peptide-functionalized TPGS micellar nanosystems to deliver 10-hydroxycampothecin for enhanced cancer chemotherapy.","authors":"Mozhi, Anbu; Ahmad, Israr; Kaleem, Qari Muhammad; Tuguntaev, Ruslan G; Eltahan, Ahmed Shaker; Wang, Chen; Yang, Rong; Li, Chan; Liang, Xing-Jie","year":2018,"journal":"International journal of pharmaceutics, 547(1-2), 582-592","doi":"10.1016/j.ijpharm.2018.05.074","pmid":"29859925","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03816","title":"Histone-Mimetic Gold Nanoparticles as Versatile Scaffolds for Gene Transfer and Chromatin Analysis.","authors":"Munsell, Erik V; Fang, Bing; Sullivan, Millicent O","year":2018,"journal":"Bioconjugate chemistry, 29(11), 3691-3704","doi":"10.1021/acs.bioconjchem.8b00611","pmid":"30350573","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03817","title":"Growth hormone-releasing hormone receptor antagonists modify molecular machinery in the progression of prostate cancer.","authors":"Muñoz-Moreno, Laura; Schally, Andrew V; Prieto, Juan C; Carmena, M José; Bajo, Ana M","year":2018,"journal":"The Prostate, 78(12), 915-926","doi":"10.1002/pros.23648","pmid":"29748961","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03818","title":"A randomized, double-blind, placebo-controlled, dose-finding trial with Lolium perenne peptide immunotherapy.","authors":"Mösges, R; Kasche, E M; Raskopf, E; Singh, J; Sohlich, L; Astvatsatourov, A; Shah-Hosseini, K; Pirotton, S; Haazen, L; Durham, S R; Legon, T; Zadoyan, G; Shamji, M H","year":2018,"journal":"Allergy, 73(4), 896-904","doi":"10.1111/all.13358","pmid":"29150857","tags":["immunotherapy","clinical-trials"],"studyType":"rct","evidenceStrength":"moderate","keyFinding":"A short-course peptide immunotherapy using ryegrass pollen peptides (LPP) significantly reduced allergic eye reactions in grass pollen-allergic adults. The 170 μg dose was the sweet spot: 51.2% of patients improved by at least one concentration step on the conjunctival provocation test (vs. 25.6% on placebo, p=0.023), and 39% became completely non-reactive to the allergen challenge compared to only 18% on placebo.\n\nThe treatment also triggered dose-dependent increases in protective IgG4 antibodies — 1.6-fold at 70 μg, 3.1-fold at 170 μg, and 3.9-fold at 370 μg — confirming that the immune system was being reprogrammed to tolerate the allergen. All of this was achieved with just 3-4 weeks of weekly injections, far shorter than conventional allergy immunotherapy.","whyItMatters":"Traditional allergy immunotherapy (allergy shots) typically requires months to years of treatment. This peptide-based approach achieved significant clinical improvement and immune changes in just three weeks of injections. If confirmed in larger trials, this could dramatically reduce the burden of allergy treatment for the millions of people who suffer from grass pollen allergies each year.","specificNumbers":"n=198 · 3 doses tested: 70, 170, 370 μg · 51.2% improved at 170 μg vs 25.6% placebo (p=0.023) · 39% became non-reactive vs 18% placebo · IgG4 increased 3.1-fold at 170 μg · 3-4 weeks treatment duration","methodology":"This was a prospective, double-blind, placebo-controlled phase IIb dose-finding trial. 198 grass pollen-allergic adults were randomized to receive placebo or one of three cumulative doses (70, 170, or 370 μg) of Lolium perenne peptides via weekly subcutaneous injections over 2-4 weeks. Efficacy was measured using conjunctival provocation tests (dropping allergen into the eye and measuring the reaction) at baseline and after treatment. Blood samples were taken to measure changes in allergen-specific antibodies.","limitations":"As a phase IIb dose-finding study, the sample size (198 total, ~50 per arm) is moderate and primarily designed to identify the optimal dose, not to provide definitive proof of efficacy. The primary outcome was a laboratory provocation test rather than real-world symptom scores during pollen season. Longer follow-up would be needed to assess durability of the effect. The abstract's description of antibody results appears partially truncated."},{"rthcId":"RPEP-03819","title":"Effect of the Aspect Ratio of Coiled-Coil Protein Carriers on Cellular Uptake.","authors":"Nakayama, Norihisa; Takaoka, Sho; Ota, Megumi; Takagaki, Kentaro; Sano, Ken-Ichi","year":2018,"journal":"Langmuir : the ACS journal of surfaces and colloids, 34(47), 14286-14293","doi":"10.1021/acs.langmuir.8b02616","pmid":"30384613","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03820","title":"Incretin hormones: Their role in health and disease.","authors":"Nauck, Michael A; Meier, Juris J","year":2018,"journal":"Diabetes, obesity & metabolism, 20 Suppl 1, 5-21","doi":"10.1111/dom.13129","pmid":"29364588","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03821","title":"Immunotherapy for hepatitis B in the direct acting antiviral era: Reevaluating the thymosin α1 efficacy trials in the light of a combination therapy approach.","authors":"Naylor, P H; Mutchnick, M G","year":2018,"journal":"Journal of viral hepatitis, 25(1), 4-9","doi":"10.1111/jvh.12807","pmid":"29052304","tags":["thymosin-alpha-1","hepatitis-b","immunotherapy"],"studyType":"review","evidenceStrength":"review","keyFinding":"Combining thymosin α1 (Tα1), an immune-boosting peptide, with nucleos(t)ide analog antivirals (NUCs) may be more effective at clearing chronic hepatitis B than either approach alone. While NUCs suppress viral replication and Tα1 can help eliminate viral surface markers (HBsAg and HBeAg) in select patients, the combination leverages both viral suppression and immune activation. Small studies using Tα1 with NUCs showed encouraging results, and clinical trials combining entecavir with Tα1 were underway at the time of publication.","whyItMatters":"Chronic hepatitis B infects hundreds of millions of people worldwide, and current antiviral treatments suppress the virus but rarely cure it. A functional cure requires the immune system to clear remaining virus — exactly what thymosin α1 aims to do. This review makes the case that combining immune stimulation with antiviral suppression could achieve what neither approach accomplishes alone: actual resolution of chronic HBV infection.","specificNumbers":"","methodology":"Narrative review summarizing existing clinical trial data on thymosin α1 efficacy in hepatitis B, with a focus on combination therapy approaches using Tα1 alongside nucleoside/nucleotide analogs. The review reanalyzed previous Tα1 monotherapy trials in the context of modern combination therapy strategies.","limitations":"The combination therapy evidence cited comes from small studies, not large randomized trials. The review is somewhat advocacy-oriented, making the case for Tα1 combination therapy rather than providing a balanced assessment of all approaches. Clinical trials referenced were anticipated but results were not yet available at publication time. Individual patient response to Tα1 varies considerably."},{"rthcId":"RPEP-03822","title":"Developments in Cell-Penetrating Peptides as Antiviral Agents and as Vehicles for Delivery of Peptide Nucleic Acid Targeting Hepadnaviral Replication Pathway.","authors":"Ndeboko, Bénédicte; Hantz, Olivier; Lemamy, Guy Joseph; Cova, Lucyna","year":2018,"journal":"Biomolecules, 8(3)","doi":"10.3390/biom8030055","pmid":"30013006","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03823","title":"Genetic background influences cardiac phenotype in murine chronic kidney disease.","authors":"Neuburg, Samantha; Dussold, Corey; Gerber, Claire; Wang, Xueyan; Francis, Connor; Qi, Lixin; David, Valentin; Wolf, Myles; Martin, Aline","year":2018,"journal":"Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 33(7), 1129-1137","doi":"10.1093/ndt/gfx332","pmid":"29309658","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03824","title":"Blockade of analgesic effects following systemic administration of N-methyl-kyotorphin, NMYR and arginine in mice deficient of preproenkephalin or proopiomelanocortin gene.","authors":"Neyama, Hiroyuki; Hamada, Yusuke; Tsukahara, Ryoko; Narita, Minoru; Tsukamoto, Kazuhiro; Ueda, Hiroshi","year":2018,"journal":"Peptides, 107, 10-16","doi":"10.1016/j.peptides.2018.06.010","pmid":"30040980","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03825","title":"Thioether Macrocyclic Peptides Selected against TET1 Compact Catalytic Domain Inhibit TET1 Catalytic Activity.","authors":"Nishio, Kosuke; Belle, Roman; Katoh, Takayuki; Kawamura, Akane; Sengoku, Toru; Hanada, Kazuharu; Ohsawa, Noboru; Shirouzu, Mikako; Yokoyama, Shigeyuki; Suga, Hiroaki","year":2018,"journal":"Chembiochem : a European journal of chemical biology, 19(9), 979-985","doi":"10.1002/cbic.201800047","pmid":"29665240","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03826","title":"Differential consequences of neurokinin receptor 1 and 2 antagonists in metastatic breast carcinoma cells; Effects independent of Substance P.","authors":"Nizam, Esra; Erin, Nuray","year":2018,"journal":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 108, 263-270","doi":"10.1016/j.biopha.2018.09.013","pmid":"30223097","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03827","title":"Survival analysis of multiple peptide vaccination for the selection of correlated peptides in urological cancers.","authors":"Noguchi, Masanori; Koga, Noriko; Moriya, Fukuko; Suekane, Shigetaka; Yutani, Shigeru; Yamada, Akira; Shichijo, Shigeki; Kakuma, Tatuyuki; Itoh, Kyogo","year":2018,"journal":"Cancer science, 109(9), 2660-2669","doi":"10.1111/cas.13709","pmid":"29938870","tags":[],"studyType":"retrospective-cohort","evidenceStrength":"low-moderate","keyFinding":"By analyzing survival data from 265 urological cancer patients treated with personalized peptide vaccination (PPV), researchers identified specific peptides associated with significantly longer survival. In castration-resistant prostate cancer (CRPC), five peptides (SART3-109, PTHrP-102, HNPRL-140, SART3-302, and Lck-90) were linked to improved survival. In advanced urothelial cancer (UC), five different peptides (EGF-R-800, Lck-486, PSMA-624, CypB-129, and SART3-734) showed survival benefit.\n\nAll tumor-associated antigens coding for these candidate peptides were confirmed to be expressed in actual tumor tissues by immunohistochemistry, validating that the vaccines target proteins present on the cancers.","whyItMatters":"Peptide cancer vaccines have shown strong immune responses but disappointing clinical results. This study suggests the problem may be peptide selection — by identifying which specific peptides correlate with longer survival, researchers can optimize personalized vaccination to include the most effective peptides for each cancer type, potentially improving outcomes.","specificNumbers":"n=265 · 154 CRPC + 111 UC patients · 5 clinical trials · 5 survival-correlated peptides per cancer type · Hazard ratio <1.0 with p<0.05 for each · Tumor antigen expression confirmed in 24 tissue samples","methodology":"Retrospective survival analysis of 265 urological cancer patients from 5 clinical trials of personalized peptide vaccination. Patients received different peptide combinations based on their HLA type and pre-existing immunity. The Cox proportional hazards model evaluated which individual peptides were associated with overall survival. Tumor antigen expression was verified by immunohistochemistry in 10 prostate cancer tissues, 4 metastatic lymph nodes, and 10 urothelial cancer tissues.","limitations":"This is a retrospective analysis of pooled trial data, not a prospective randomized study testing specific peptide combinations. Multiple comparisons increase the risk of false positives. The personalized nature of PPV means each patient received different peptides, making direct comparisons difficult. Sample sizes per peptide subgroup are likely small. The survival associations are correlative, not causal."},{"rthcId":"RPEP-03828","title":"The Atlantic salmon (Salmo salar) antimicrobial peptide cathelicidin-2 is a molecular host-associated cue for the salmon louse (Lepeophtheirus salmonis).","authors":"Núñez-Acuña, Gustavo; Gallardo-Escárate, Cristian; Fields, David M; Shema, Steven; Skiftesvik, Anne Berit; Ormazábal, Ignacio; Browman, Howard I","year":2018,"journal":"Scientific reports, 8(1), 13738","doi":"10.1038/s41598-018-31885-6","pmid":"30213966","tags":[],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"The antimicrobial peptide cathelicidin-2 (Cath-2) released from Atlantic salmon skin serves a completely unexpected second function: it's the chemical signal that sea lice (Lepeophtheirus salmonis) use to find their hosts. When exposed to Cath-2 at concentrations of 7, 70, and 700 ppb, sea lice copepodids showed triggered chemosensory neural activity, altered swimming behavior, and upregulated chemosensory-related genes.\n\nThis reveals a remarkable evolutionary twist — a peptide that evolved to defend against microbial infection is being exploited by a parasite as a homing beacon to locate its host.","whyItMatters":"Sea lice are the most costly parasite in salmon aquaculture, causing billions in losses annually. Discovering that they use a specific antimicrobial peptide to find hosts opens entirely new approaches to parasite control — potentially blocking the chemical signal or developing decoys. More broadly, it reveals that antimicrobial peptides can have ecological functions beyond pathogen defense, fundamentally expanding our understanding of what these peptides do in nature.","specificNumbers":"Cath-2 tested at 0, 7, 70, and 700 ppb · Neurophysiology, behavior, and transcriptomics all consistent · Chemosensory neural activity triggered · Swimming behavior altered · Chemosensory genes upregulated","methodology":"Sea lice copepodids were exposed to four concentrations of salmon cathelicidin-2 (0, 7, 70, 700 ppb). Researchers measured three independent outcomes: neural activity (neurophysiology), swimming behavior (behavioral assays), and gene expression profiles (transcriptomics). The convergence of all three lines of evidence confirmed the peptide's role as a host-associated chemical cue.","limitations":"The study was conducted under laboratory conditions that may not fully replicate the complex chemical environment of the ocean. The abstract doesn't report whether other salmon-derived molecules were tested as controls. It's unclear whether Cath-2 is the only chemical cue sea lice use or one of several. The concentrations tested may or may not reflect natural levels released from salmon skin."},{"rthcId":"RPEP-03829","title":"Present status and future perspective of peptide-based vaccine therapy for urological cancer.","authors":"Obara, Wataru; Kanehira, Mitsugu; Katagiri, Toyomasa; Kato, Renpei; Kato, Yoichiro; Takata, Ryo","year":2018,"journal":"Cancer science, 109(3), 550-559","doi":"10.1111/cas.13506","pmid":"29345737","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03830","title":"Mechanistic implication of decreased plasma atrial natriuretic peptide level for transient rise in the atrial capture threshold early after ICD or CRT-D implantation.","authors":"Ogawa, Kojiro; Yoshida, Kentaro; Uehara, Yoshiko; Ebine, Mari; Kimata, Akira; Nishina, Hidetaka; Takeyasu, Noriyuki; Noguchi, Yuichi; Ieda, Masaki; Aonuma, Kazutaka; Nogami, Akihiko","year":2018,"journal":"Journal of interventional cardiac electrophysiology : an international journal of arrhythmias and pacing, 53(1), 131-140","doi":"10.1007/s10840-018-0409-0","pmid":"30019272","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03831","title":"Role of Substance P and Its Receptor Neurokinin 1 in Chronic Prurigo: A Randomized, Proof-of-Concept, Controlled Trial with Topical Aprepitant.","authors":"Ohanyan, Tatevik; Schoepke, Nicole; Eirefelt, Stefan; Hoey, Gert; Koopmann, Witte; Hawro, Tomasz; Maurer, Marcus; Metz, Martin","year":2018,"journal":"Acta dermato-venereologica, 98(1), 26-31","doi":"10.2340/00015555-2780","pmid":"28853492","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Biomarker findings confirmed substance P/NK1R involvement:\n- Substance P serum levels were increased in chronic prurigo patients compared to controls\n- NK1R expression was higher in lesional versus non-lesional skin\n\nClinical trial results (randomized, placebo-controlled, split-sided, double-blind):\n- Topical aprepitant reduced itch intensity by >50% from baseline by day 28 (VAS change: -35.2)\n- Placebo vehicle also reduced itch by >50% (VAS change: -38.1)\n- No significant difference between groups (p=0.76)\n- Overall clinical scores improved in both groups with no significant between-group difference (p=0.32)\n\nThe strong placebo response in the split-sided design likely obscured any treatment effect.","whyItMatters":"Chronic prurigo is a common and distressing condition with limited treatment options. This study provides important evidence at two levels: the biomarker data confirms that substance P and NK1R are legitimate therapeutic targets in this disease, while the negative clinical trial result reveals a critical methodological lesson — split-sided trial designs may not work for systemic conditions where treating one side can affect the other through circulating neuropeptides. This informs future trial design for neuropeptide-targeted itch therapies.","specificNumbers":"","methodology":"The study had two components: (1) A case-control biomarker analysis comparing substance P serum levels and cutaneous NK1R expression between chronic prurigo patients and healthy controls, and between lesional and non-lesional skin within patients. (2) A randomized, placebo-controlled, split-sided (one side of body gets drug, other gets placebo), double-blind proof-of-concept trial of topical aprepitant in chronic prurigo patients. Primary outcome was pruritus intensity measured by visual analogue scale (VAS) at day 28.","limitations":"The split-sided trial design is a major limitation — applying drug to one side and placebo to the other may not control for systemic effects of topical absorption or for psychological effects of knowing some part of the body is being treated. The sample size is not specified in the abstract but was likely small for a proof-of-concept study. Topical drug penetration to reach NK1R on nerve fibers may have been insufficient. The >50% improvement in both groups suggests a strong placebo effect or natural disease fluctuation. The 28-day duration may be too short for a chronic condition."},{"rthcId":"RPEP-03832","title":"CPP-Ts: a new intracellular calcium channel modulator and a promising tool for drug delivery in cancer cells.","authors":"Oliveira-Mendes, Bárbara Bruna Ribeiro de; Horta, Carolina Campolina Rebello; do Carmo, Anderson Oliveira; Biscoto, Gabriela Lago; Sales-Medina, Douglas Ferreira; Leal, Hortênsia Gomes; Brandão-Dias, Pedro Ferreira Pinto; Miranda, Sued Eustáquio Mendes; Aguiar, Carla Jeane; Cardoso, Valbert Nascimento; de Barros, André Luis Branco; Chávez-Olortégui, Carlos; Leite, M Fátima; Kalapothakis, Evanguedes","year":2018,"journal":"Scientific reports, 8(1), 14739","doi":"10.1038/s41598-018-33133-3","pmid":"30282983","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03833","title":"Biosynthetic Proteases That Catalyze the Macrocyclization of Ribosomally Synthesized Linear Peptides.","authors":"Ongpipattanakul, Chayanid; Nair, Satish K","year":2018,"journal":"Biochemistry, 57(23), 3201-3209","doi":"10.1021/acs.biochem.8b00114","pmid":"29553721","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03834","title":"The Intestinotrophic Effects of Glucagon-Like Peptide-2 in Relation to Intestinal Neoplasia.","authors":"Orhan, Adile; Gögenur, Ismail; Kissow, Hannelouise","year":2018,"journal":"The Journal of clinical endocrinology and metabolism, 103(8), 2827-2837","doi":"10.1210/jc.2018-00655","pmid":"29741675","tags":["glp-2","gastrointestinal","cancer-risk"],"studyType":"Review","evidenceStrength":"Moderate","keyFinding":"GLP-2 stimulates intestinal growth through secondary mediators and Akt phosphorylation signaling, making it therapeutic for conditions like short bowel syndrome. However, rodent studies have shown that exogenous GLP-2 increases the growth and incidence of colon adenomas, raising concern that GLP-2 treatment could promote intestinal tumor development or progression.\n\nClinical studies show that exogenous GLP-2 treatment (as teduglutide) is well tolerated for up to 30 months, but the safety of longer treatment periods regarding intestinal cancer risk has not been established. The association between GLP-2 treatment and intestinal neoplasia in humans remains unclear.","whyItMatters":"Teduglutide (a GLP-2 analog) is an FDA-approved treatment for short bowel syndrome, a life-threatening condition where patients cannot absorb enough nutrition. The drug works by stimulating intestinal tissue growth — but this same growth-promoting property raises a critical safety question: could it also promote intestinal cancers? This review highlights a real clinical dilemma where a drug that provides essential benefit for one condition could theoretically increase risk of another. Patients on long-term teduglutide need monitoring, and the field needs better long-term safety data.","specificNumbers":"Up to 30 months of tolerated clinical use · rodent data showing increased adenoma growth and incidence · Akt phosphorylation pathway · teduglutide (approved GLP-2 analog)","methodology":"Narrative review based on PubMed literature searches using English keywords. The authors reviewed all published experimental (animal) and clinical (human) studies examining GLP-2's relationship to intestinal neoplasia. The review covers both the growth-stimulating mechanisms of GLP-2 and the available safety data from clinical use of teduglutide.","limitations":"The studies on GLP-2 and intestinal neoplasia are described as 'sparse,' limiting the strength of conclusions. The rodent tumor data may not directly translate to humans. Clinical safety data extends only to 30 months. As a narrative rather than systematic review, study selection may not be comprehensive. The review cannot establish causation between GLP-2 treatment and cancer risk in humans."},{"rthcId":"RPEP-03835","title":"Calcitonin-gene-related peptide pathway mAbs and migraine prevention.","authors":"Paemeleire, Koen; MaassenVanDenBrink, Antoinette","year":2018,"journal":"Current opinion in neurology, 31(3), 274-280","doi":"10.1097/WCO.0000000000000548","pmid":"29432219","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Phase 2 and Phase 3 trial data for all four CGRP pathway antibodies confirmed consistent efficacy for both episodic and chronic migraine prevention. The efficacy was described as modest over placebo and broadly comparable to available oral preventive treatments.\n\nThe key differentiator was tolerability: safety reviews found no significant difference in total adverse events between the antibodies and placebo injections, except possibly for dizziness. Common side effects (upper respiratory tract infection, nasopharyngitis, nausea, injection-site pain, back pain) occurred at similar rates in treatment and placebo groups. The mechanism of action appears to be primarily peripheral, though central nervous system contributions could not be ruled out.","whyItMatters":"Migraine affects roughly 1 billion people worldwide and is a leading cause of disability. Many patients stop taking oral preventive medications because of side effects like weight gain, fatigue, and cognitive issues. The CGRP antibodies represented a paradigm shift — the first migraine treatments designed based on understanding the underlying peptide biology, offering comparable effectiveness with dramatically better tolerability. This review captured the evidence at a pivotal moment just before these drugs reached the market.","specificNumbers":"","methodology":"This is a narrative review article summarizing published Phase 2 and Phase 3 clinical trial data for four CGRP pathway monoclonal antibodies: eptinezumab, fremanezumab, galcanezumab (which bind the CGRP ligand), and erenumab (which binds the CGRP receptor). The review covers efficacy data, safety and tolerability profiles, pharmacokinetics, and mechanism of action.","limitations":"At the time of this review, only short-term safety data were available — long-term effects of blocking the CGRP pathway (which has roles in cardiovascular protection and wound healing) remained unknown. The review noted that the efficacy was modest over placebo, raising questions about cost-effectiveness. Phase 3 data were still emerging, and the authors noted many more publications were expected. Additionally, which patients would respond best to CGRP-targeting therapy was not yet well understood."},{"rthcId":"RPEP-03836","title":"Evolving Role of Natriuretic Peptides from Diagnostic Tool to Therapeutic Modality.","authors":"Pagel-Langenickel, Ines","year":2018,"journal":"Advances in experimental medicine and biology, 1067, 109-131","doi":"10.1007/5584_2018_143","pmid":"29411335","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"This review traces the evolution of natriuretic peptides from basic biology to clinical application. ANP and BNP are released by the heart during overload and act as natural counterweights to the renin-angiotensin-aldosterone system — lowering blood pressure, reducing fluid retention, and inhibiting harmful cardiac remodeling.\n\nBNP and its precursor fragment NT-proBNP have become established diagnostic and prognostic biomarkers for heart failure. However, the body's natriuretic peptide response during heart failure is insufficient to prevent disease progression. Of various therapeutic strategies attempted — including synthetic peptide analogs and inhibition of the enzyme that degrades natriuretic peptides (NEP) — only the combined NEP inhibitor/angiotensin receptor blocker sacubitril/valsartan demonstrated clinical success in reducing cardiovascular mortality and morbidity.","whyItMatters":"Heart failure affects over 60 million people worldwide. Natriuretic peptides represent one of the most successful peptide-to-medicine stories: the same molecules used for diagnosis (BNP blood tests) also became therapeutic targets. The success of sacubitril/valsartan — which works by preventing natriuretic peptide breakdown — fundamentally changed heart failure treatment guidelines and demonstrated that augmenting endogenous peptide systems can save lives.","specificNumbers":"","methodology":"This is a narrative review article synthesizing published research on natriuretic peptide biology, their role as biomarkers, and therapeutic strategies targeting the natriuretic peptide system. It covers basic science, clinical diagnostics, and drug development outcomes.","limitations":"As a narrative review, this paper summarizes existing literature rather than presenting new data. It reflects the state of knowledge as of 2018, so more recent developments in natriuretic peptide therapeutics are not covered. The review focuses primarily on heart failure, with less coverage of natriuretic peptide roles in other conditions like kidney disease or metabolic syndrome."},{"rthcId":"RPEP-03837","title":"Evaluation of the osteoprotective potential of whey derived-antioxidative (YVEEL) and angiotensin-converting enzyme inhibitory (YLLF) bioactive peptides in ovariectomised rats.","authors":"Pandey, Masum; Kapila, Suman; Kapila, Rajeev; Trivedi, Ritu; Karvande, Anirudh","year":2018,"journal":"Food & function, 9(9), 4791-4801","doi":"10.1039/c8fo00620b","pmid":"30128468","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03838","title":"Osteoanabolic activity of whey-derived anti-oxidative (MHIRL and YVEEL) and angiotensin-converting enzyme inhibitory (YLLF, ALPMHIR, IPA and WLAHK) bioactive peptides.","authors":"Pandey, Masum; Kapila, Rajeev; Kapila, Suman","year":2018,"journal":"Peptides, 99, 1-7","doi":"10.1016/j.peptides.2017.11.004","pmid":"29122669","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03839","title":"Peptide-Binding Groove Contraction Linked to the Lack of T Cell Response: Using Complex Structure and Energy To Identify Neoantigens.","authors":"Pang, Yuan-Ping; Elsbernd, Laura R; Block, Matthew S; Markovic, Svetomir N","year":2018,"journal":"ImmunoHorizons, 2(7), 216-225","doi":"10.4049/immunohorizons.1800048","pmid":"31022692","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Molecular dynamics simulations of 12 oligopeptides bound to HLA molecules revealed a previously unknown mechanism: some peptides cause the HLA binding groove to contract upon binding, making the peptide-HLA complex incompatible with T cell receptor recognition. This means that just because a peptide can bind to an HLA molecule does not mean it will trigger an immune response.\n\nBased on this insight, the authors developed SEFF12MC, an atom-based computational method that predicts immunogenicity by assessing whether a peptide-HLA complex can further bind to a T cell receptor. SEFF12MC achieved a 100% success rate in predicting immunogenicity of the 12 test peptides, compared to only 25-50% success rates for 11 existing residue-based methods including NetMHC-4.0.","whyItMatters":"Personalized peptide cancer vaccines are one of the most promising frontiers in cancer immunotherapy, but their development has been slowed by the inability to accurately predict which peptides will actually stimulate an immune response. Current methods correctly identify immunogenic peptides only 25-50% of the time. A tool that achieves 100% accuracy — even on a small test set — could dramatically accelerate the development of effective personalized cancer vaccines.","specificNumbers":"","methodology":"The researchers performed molecular dynamics simulations of 12 oligopeptides bound to HLA-A2 molecules to study the structural dynamics of peptide-HLA complexes. They analyzed conformational changes in the binding groove and the interface with T cell receptors. Based on these structural insights, they developed the SEFF12MC prediction method, which uses the three-dimensional structure and binding energy of peptide-HLA complexes to assess their ability to interact with T cell receptors. Results were benchmarked against 11 publicly available prediction methods.","limitations":"The method was validated on only 12 peptides, which is a very small test set. The authors acknowledge that further validation and refinements are required. The simulations focused on a single HLA type (HLA-A2), and applicability to other HLA alleles is unknown. The computational approach requires molecular dynamics simulations, which are resource-intensive. Clinical validation of the predictions has not been performed."},{"rthcId":"RPEP-03840","title":"Thymosin alpha 1 treatment for patients with sepsis.","authors":"Pei, Fei; Guan, Xiangdong; Wu, Jianfeng","year":2018,"journal":"Expert opinion on biological therapy, 18(sup1), 71-76","doi":"10.1080/14712598.2018.1484104","pmid":"30063866","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across the reviewed clinical studies, thymosin alpha-1 treatment — both alone and in combination with anti-inflammatory therapies — reduced mortality rates in sepsis patients, improved HLA-DR expression on monocytes (a key marker of immune competence), and diminished the incidence of secondary infections. The authors identify Tα1 as a promising adjuvant therapy but note that the heterogeneity of sepsis makes it difficult to generalize results. They recommend that future trials specifically enroll immunosuppressed sepsis patients to better demonstrate efficacy.","whyItMatters":"Sepsis remains one of the leading causes of death in hospitals worldwide, and treatment options beyond antibiotics and supportive care are limited. An immune-modulating peptide that can restore the immune system's ability to fight infection — rather than just suppressing inflammation — could fill a critical gap in sepsis treatment, particularly for patients whose immune systems have become exhausted.","specificNumbers":"","methodology":"Systematic review of clinical studies on Tα1 treatment for sepsis and septic shock, drawn from both English and Chinese language databases. Studies evaluated Tα1 as monotherapy and in combination with anti-inflammatory agents. Outcomes assessed included mortality, immune function markers (HLA-DR on monocytes), and secondary infection rates.","limitations":"Sepsis is extremely heterogeneous, making it difficult to generalize results across all patients. Most existing studies did not specifically select immunosuppressed patients, who are theoretically most likely to benefit. The review includes Chinese-language databases, where study quality and reporting standards may vary. Specific mortality reduction percentages and sample sizes were not detailed in the abstract. The review was published before larger randomized trials could provide definitive evidence."},{"rthcId":"RPEP-03841","title":"Cell penetrating peptides in ocular drug delivery: State of the art.","authors":"Pescina, S; Ostacolo, C; Gomez-Monterrey, I M; Sala, M; Bertamino, A; Sonvico, F; Padula, C; Santi, P; Bianchera, A; Nicoli, S","year":2018,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 284, 84-102","doi":"10.1016/j.jconrel.2018.06.023","pmid":"29913221","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03842","title":"In vivo antitumor function of tumor antigen-specific CTLs generated in the presence of OX40 co-stimulation in vitro.","authors":"Pham Minh, Ngoc; Murata, Satoshi; Kitamura, Naomi; Ueki, Tomoyuki; Kojima, Masatsugu; Miyake, Toru; Takebayashi, Katsushi; Kodama, Hirokazu; Mekata, Eiji; Tani, Masaji","year":2018,"journal":"International journal of cancer, 142(11), 2335-2343","doi":"10.1002/ijc.31244","pmid":"29313971","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03843","title":"Intracellular Delivery via Noncharged Sequence-Defined Cell-Penetrating Oligomers.","authors":"Phan, Ngoc N; Li, Connie; Alabi, Christopher A","year":2018,"journal":"Bioconjugate chemistry, 29(8), 2628-2635","doi":"10.1021/acs.bioconjchem.8b00336","pmid":"29953207","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Researchers discovered a new class of noncharged cell-penetrating oligoTEAs (CPOTs) that entered cells extensively and rapidly across multiple cell lines with low toxicity. These synthetic oligomers outperformed R9 — a widely used nine-arginine cell-penetrating peptide — in cellular uptake efficiency.\n\nUnlike traditional cationic cell-penetrating peptides that rely on positive charges (which cause unwanted biological interactions and rapid degradation), CPOTs achieve cell entry through a charge-independent mechanism. This makes them more stable in serum and better candidates for delivering water-soluble drugs inside cells.","whyItMatters":"Cell-penetrating peptides (CPPs) have been studied for decades as drug delivery tools, but their positive charge causes problems — they interact nonspecifically with biological molecules, trigger unwanted immune responses, and are quickly degraded by enzymes. This discovery of noncharged alternatives that outperform traditional CPPs addresses these fundamental limitations and could unlock more practical intracellular drug delivery systems for therapeutics that need to reach targets inside cells.","specificNumbers":"Outperformed R9 CPP in uptake · Low cytotoxicity · Multiple cell lines tested · Noncharged design · Sequence-defined architecture","methodology":"Researchers synthesized a library of noncharged sequence-defined oligoTEAs and screened their cell-penetrating ability across different cell lines. Cellular uptake was quantified using fluorescence measurements and compared head-to-head against R9 peptide (a standard CPP). Cytotoxicity was assessed to ensure safety. The mechanism of entry and delivery efficiency for hydrophilic small molecules were characterized.","limitations":"All experiments were conducted in vitro using cell lines, which may not predict in vivo performance. The study focused on small-molecule cargo delivery — whether CPOTs can deliver larger payloads like proteins or nucleic acids was not demonstrated. Long-term stability, biodistribution, and safety in animals remain untested. The comparison was against R9 alone; performance against other advanced CPPs was not assessed."},{"rthcId":"RPEP-03844","title":"Serum thymosin alpha 1 levels in normal and pathological conditions.","authors":"Pica, Francesca; Gaziano, Roberta; Casalinuovo, Ida Antonia; Moroni, Gabriella; Buè, Cristina; Limongi, Dolores; D'Agostini, Cartesio; Tomino, Carlo; Perricone, Roberto; Palamara, Anna Teresa; Sinibaldi Vallebona, Paola; Garaci, Enrico","year":2018,"journal":"Expert opinion on biological therapy, 18(sup1), 13-21","doi":"10.1080/14712598.2018.1474197","pmid":"30063864","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03845","title":"Regenerative and Protective Actions of the GHK-Cu Peptide in the Light of the New Gene Data.","authors":"Pickart, Loren; Margolina, Anna","year":2018,"journal":"International journal of molecular sciences, 19(7)","doi":"10.3390/ijms19071987","pmid":"29986520","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03846","title":"Regenerative and Protective Actions of the GHK-Cu Peptide in the Light of the New Gene Data.","authors":"Pickart, Loren; Vasquez-Soltero, Jessica Michelle; Margolina, Anna","year":2018,"journal":"Cosmetics, 5(2), 29","doi":"10.3390/cosmetics5020029","pmid":"30175950","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03847","title":"Novel heart failure biomarkers: why do we fail to exploit their potential?","authors":"Piek, Arnold; Du, Weijie; de Boer, Rudolf A; Silljé, Herman H W","year":2018,"journal":"Critical reviews in clinical laboratory sciences, 55(4), 246-263","doi":"10.1080/10408363.2018.1460576","pmid":"29663841","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03848","title":"All-Electronic Quantification of Neuropeptide-Receptor Interaction Using a Bias-Free Functionalized Graphene Microelectrode.","authors":"Ping, Jinglei; Vishnubhotla, Ramya; Xi, Jin; Ducos, Pedro; Saven, Jeffery G; Liu, Renyu; Johnson, Alan T Charlie","year":2018,"journal":"ACS nano, 12(5), 4218-4223","doi":"10.1021/acsnano.7b07474","pmid":"29634231","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03849","title":"In vitro effect of green tea and turmeric extracts on GLP-1 and CCK secretion: the effect of gastrointestinal digestion.","authors":"Planes-Muñoz, David; López-Nicolás, Rubén; González-Bermúdez, Carlos A; Ros-Berruezo, Gaspar; Frontela-Saseta, Carmen","year":2018,"journal":"Food & function, 9(10), 5245-5250","doi":"10.1039/c8fo01334a","pmid":"30226521","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03850","title":"Reproductive performance of male mice after hypothalamic ghrelin administration.","authors":"Poretti, María Belén; Frautschi, Camila; Luque, Eugenia; Bianconi, Santiago; Martini, Ana Carolina; Stutz, Graciela; Vincenti, Laura; Santillán, Maria Emilia; Ponzio, Marina; Schiöth, Helgi B; Fiol de Cuneo, Marta; Carlini, Valeria Paola","year":2018,"journal":"Reproduction (Cambridge, England), 156(2), 121-132","doi":"10.1530/REP-17-0535","pmid":"29794024","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03851","title":"Self-assembling diphenylalanine peptide nanotubes selectively eradicate bacterial biofilm infection.","authors":"Porter, Simon L; Coulter, Sophie M; Pentlavalli, Sreekanth; Thompson, Thomas P; Laverty, Garry","year":2018,"journal":"Acta biomaterialia, 77, 96-105","doi":"10.1016/j.actbio.2018.07.033","pmid":"30031161","tags":[],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Self-assembling peptide nanotubes made from diphenylalanine (FF) completely eradicated mature Staphylococcus aureus biofilms — the first time peptide nanotubes have been shown to destroy bacterial biofilms. The NH2-FF-COOH variant was most effective, achieving greater than 99.9% biofilm reduction at 5 mg/mL and complete biofilm kill at 10 mg/mL after 24 hours, with minimal toxicity to mammalian cells.\n\nScanning electron microscopy revealed the nanotubes work by degrading the biofilm's protective polysaccharide matrix and disrupting bacterial cell membranes through ion channel formation and surfactant-like action. Switching to D-amino acid isomers (NH2-ff-COOH) maintained antibiofilm activity, while amidated forms (NH2-FF-NH2) were more toxic and less effective.","whyItMatters":"Bacterial biofilms are one of the biggest unsolved problems in medicine. These slimy communities of bacteria are 10 to 10,000 times more resistant to antibiotics than free-floating bacteria, causing chronic infections on medical devices, wounds, and implants. This study is the first to show that simple two-amino-acid peptide nanotubes can destroy these biofilms entirely. Because diphenylalanine peptides self-assemble into nanostructures spontaneously, they could be relatively cheap and easy to manufacture compared to complex antibiotics.","specificNumbers":">99.9% biofilm reduction at 5 mg/mL · complete kill at 10 mg/mL · 24h exposure · >3 Log10 CFU/mL reduction · biofilms 10-10,000× more antibiotic-resistant than planktonic bacteria","methodology":"The researchers synthesized three variants of diphenylalanine peptide nanotubes with different terminal functional groups. They tested antibacterial activity against both planktonic (free-floating) and biofilm forms of hospital-associated bacteria, including S. aureus. Mammalian cell toxicity was assessed using fibroblasts and hemolysis assays. Scanning electron microscopy was used to visualize how the nanotubes interact with biofilm structures and bacterial membranes.","limitations":"This is an in vitro (lab-based) study. The concentrations needed to kill biofilms (5-10 mg/mL) are relatively high, and it's unclear whether these can be safely achieved in a clinical setting. Activity was primarily demonstrated against Gram-positive bacteria, with limited data on Gram-negative organisms. No animal or human testing was conducted."},{"rthcId":"RPEP-03852","title":"SAR228810: an antibody for protofibrillar amyloid β peptide designed to reduce the risk of amyloid-related imaging abnormalities (ARIA).","authors":"Pradier, Laurent; Blanchard-Brégeon, Véronique; Bohme, Andrees; Debeir, Thomas; Menager, Jean; Benoit, Patrick; Barneoud, Pascal; Taupin, Véronique; Bertrand, Philippe; Dugay, Philippe; Cameron, Béatrice; Shi, Yi; Naimi, Souad; Duchesne, Marc; Gagnaire, Marie; Weeden, Tim; Travaline, Tara; Reczek, David; Khiroug, Leonard; Slaoui, Mohamed; Brunel, Pascale; Fukuyama, Hidehiro; Ravetch, Jeffrey; Canton, Thierry; Cohen, Caroline","year":2018,"journal":"Alzheimer's research & therapy, 10(1), 117","doi":"10.1186/s13195-018-0447-y","pmid":"30486882","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03853","title":"B-type natriuretic peptide-guided therapy for heart failure (HF): a systematic review and meta-analysis of individual participant data (IPD) and aggregate data.","authors":"Pufulete, Maria; Maishman, Rachel; Dabner, Lucy; Higgins, Julian P T; Rogers, Chris A; Dayer, Mark; MacLeod, John; Purdy, Sarah; Hollingworth, William; Schou, Morten; Anguita-Sanchez, Manuel; Karlström, Patric; Shochat, Michael Kleiner; McDonagh, Theresa; Nightingale, Angus K; Reeves, Barnaby C","year":2018,"journal":"Systematic reviews, 7(1), 112","doi":"10.1186/s13643-018-0776-8","pmid":"30064502","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03854","title":"Self-assembling peptides cross-linked with genipin: resilient hydrogels and self-standing electrospun scaffolds for tissue engineering applications.","authors":"Pugliese, Raffaele; Maleki, Mahboubeh; Zuckermann, Ronald N; Gelain, Fabrizio","year":2018,"journal":"Biomaterials science, 7(1), 76-91","doi":"10.1039/c8bm00825f","pmid":"30475373","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Genipin cross-linking significantly increased the stiffness and resiliency of FAQ(LDLK)3 self-assembling peptide hydrogels in a dose- and time-dependent manner. The cross-linking also extended bioabsorption time and altered molecular arrangements.\n\nUsing the optimized protocol, researchers achieved a breakthrough: electrospinning cross-linked SAPs into nanofibers to create self-standing, water-stable, and flexible fibrous mats and micro-channels entirely made of peptides — the first time this was accomplished. This was possible because the genipin cross-links provided sufficient mechanical integrity for the peptide scaffolds to maintain their structure independently.","whyItMatters":"Self-assembling peptides have extraordinary potential for tissue engineering because they're biocompatible, biodegradable, and can be easily functionalized. But their weakness has been literal weakness — the non-covalent bonds that drive self-assembly produce soft, fragile gels. This cross-linking breakthrough solves that fundamental limitation, making all-peptide biomaterials mechanically competitive with synthetic polymers for the first time. The ability to electrospin these peptides into free-standing structures is particularly significant for neural tissue engineering.","specificNumbers":"","methodology":"The self-assembling peptide FAQ(LDLK)3 (previously validated for neural cell cultures) was cross-linked with genipin at varying concentrations and durations. The resulting hydrogels were characterized for mechanical stiffness, resiliency, bioabsorption time, and molecular arrangement using standard biomaterials characterization techniques. The optimized cross-linked peptide formulation was then electrospun to create nanofiber scaffolds. The resulting mats and micro-channels were assessed for water stability, flexibility, and structural integrity.","limitations":"The study focuses on a single self-assembling peptide (FAQ(LDLK)3) and one cross-linker (genipin), so generalizability to other SAP sequences is unknown. In vivo biocompatibility and tissue regeneration data for the cross-linked scaffolds are not presented. Long-term stability and degradation behavior under physiological conditions were not fully characterized. The electrospun scaffolds have not been tested with cells in the nanofiber format. Manufacturing scalability for clinical applications was not addressed."},{"rthcId":"RPEP-03855","title":"Chronic treatment with the mitochondrial peptide humanin prevents age-related myocardial fibrosis in mice.","authors":"Qin, Qing; Mehta, Hemal; Yen, Kelvin; Navarrete, Gerardo; Brandhorst, Sebastian; Wan, Junxiang; Delrio, Silvia; Zhang, Xin; Lerman, Lilach O; Cohen, Pinchas; Lerman, Amir","year":2018,"journal":"American journal of physiology. Heart and circulatory physiology, 315(5), H1127-H1136","doi":"10.1152/ajpheart.00685.2017","pmid":"30004252","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03856","title":"Induction of Apoptosis in Pterygium Cells by Antagonists of Growth Hormone-Releasing Hormone Receptors.","authors":"Qin, Yong Jie; Chu, Wai Kit; Huang, Li; Ng, Clara Hoi Yen; Chan, Tommy Chung Yan; Cao, Di; Yang, Cheng; Zhang, Liang; Huang, Shao Ping; Li, Juan; Lin, Hong Liang; Li, Wen Qian; Chen, Li; Schally, Andrew V; Chan, Sun On; Zhang, Hong Yang; Pang, Chi Pui","year":2018,"journal":"Investigative ophthalmology & visual science, 59(12), 5060-5066","doi":"10.1167/iovs.18-24751","pmid":"30357400","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03857","title":"Poly(propylacrylic acid)-peptide nanoplexes as a platform for enhancing the immunogenicity of neoantigen cancer vaccines.","authors":"Qiu, Feng; Becker, Kyle W; Knight, Frances C; Baljon, Jessalyn J; Sevimli, Sema; Shae, Daniel; Gilchuk, Pavlo; Joyce, Sebastian; Wilson, John T","year":2018,"journal":"Biomaterials, 182, 82-91","doi":"10.1016/j.biomaterials.2018.07.052","pmid":"30107272","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03858","title":"The Biology of Monoclonal Antibodies: Focus on Calcitonin Gene-Related Peptide for Prophylactic Migraine Therapy.","authors":"Raffaelli, Bianca; Reuter, Uwe","year":2018,"journal":"Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 15(2), 324-335","doi":"10.1007/s13311-018-0622-7","pmid":"29616494","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"All four anti-CGRP monoclonal antibodies (eptinezumab, fremanezumab, galcanezumab, and erenumab) proved effective, tolerable, and safe for migraine prevention in phase II clinical trials. Mean monthly migraine day reductions ranged from 3.4 to 6.3 days after 8-12 weeks of treatment, with placebo-subtracted benefit of 1 to 2.18 days. Up to 32% of patients achieved total migraine freedom. No substance class-specific adverse events or treatment-related serious adverse events occurred. The antibodies likely act peripherally since their large size prevents blood-brain barrier penetration, revealing that peripheral CGRP signaling plays a pivotal role in migraine.","whyItMatters":"Anti-CGRP antibodies represent the first migraine treatments specifically developed based on understanding the disease's biology — previous preventive treatments were all repurposed from other conditions. This review captures a landmark moment in headache medicine and peptide therapeutics, documenting the clinical validation of targeting the CGRP peptide pathway. The finding that these drugs work peripherally fundamentally changed our understanding of migraine as a disease.","specificNumbers":"4 mAbs reviewed · 3.4-6.3 fewer migraine days/month · placebo-subtracted benefit 1-2.18 days · up to 32% migraine freedom · 8-12 week treatment periods · CGRP is 37 amino acids · no class-specific adverse events","methodology":"This is a narrative review summarizing the biology of CGRP, the development rationale for anti-CGRP monoclonal antibodies, and the phase II clinical trial results for all four anti-CGRP antibodies being developed for migraine prevention. It covers mechanism of action, pharmacokinetics, efficacy data, and safety profiles.","limitations":"At the time of publication (2018), only phase II trial data were available; phase III results were still pending. Long-term safety data beyond the trial durations were unavailable. The review does not include comparative effectiveness data between the four antibodies. Potential vascular safety concerns and the impact of anti-drug antibodies remained unresolved questions."},{"rthcId":"RPEP-03859","title":"Neurogenic inflammation and its role in migraine.","authors":"Ramachandran, Roshni","year":2018,"journal":"Seminars in immunopathology, 40(3), 301-314","doi":"10.1007/s00281-018-0676-y","pmid":"29568973","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03860","title":"Reduction of respiratory infections in asthma patients supplemented with vitamin D is related to increased serum IL-10 and IFNγ levels and cathelicidin expression.","authors":"Ramos-Martínez, E; López-Vancell, M R; Fernández de Córdova-Aguirre, J C; Rojas-Serrano, J; Chavarría, A; Velasco-Medina, A; Velázquez-Sámano, G","year":2018,"journal":"Cytokine, 108, 239-246","doi":"10.1016/j.cyto.2018.01.001","pmid":"29402723","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Vitamin D supplementation (calcitriol) in asthma patients led to significantly increased serum levels of the anti-inflammatory cytokine IL-10 and the antiviral cytokine IFNγ, while pro-inflammatory cytokines IL-5, IL-9, and IL-13 decreased significantly. IgE and eosinophil levels also dropped, though allergen sensitivity remained unchanged.\n\nRespiratory infections were drastically reduced in the vitamin D group, and this reduction was directly related to the number of patients who had high IL-10 and IFNγ levels and expressed the antimicrobial peptide cathelicidin LL-37 in their sputum. This links vitamin D's infection-fighting benefit to its ability to stimulate natural antimicrobial peptide production.","whyItMatters":"Respiratory infections are a leading trigger of asthma exacerbations. Finding that vitamin D can reduce infections by boosting the body's own antimicrobial peptide (cathelicidin LL-37) provides a mechanistic explanation for vitamin D's protective effects and suggests a simple, low-cost adjunct therapy that could improve outcomes for asthma patients.","specificNumbers":"","methodology":"Randomized, placebo-controlled trial with 86 asthma patients aged 18-50. Both groups received standard GINA-recommended asthma treatment. The treatment group additionally received calcitriol (1,25-(OH)₂D₃) for 6 months. At baseline and 6 months, researchers performed skin prick tests, pharyngeal bacterial cultures, sputum cathelicidin LL-37 measurements, and serum quantification of IgE, eosinophils, IL-5, IL-9, IL-10, IL-13, and IFNγ.","limitations":"The sample size of 86 patients is moderate, and the study may not be powered to detect all relevant effects. Allergen sensitivity did not change, suggesting vitamin D's benefits may be limited to infection-related rather than allergic aspects of asthma. The study used calcitriol (active vitamin D) rather than standard vitamin D3 supplements, which may limit generalizability to typical supplementation regimens. Long-term effects beyond 6 months were not assessed."},{"rthcId":"RPEP-03861","title":"Changes in patient characteristics, glucose lowering treatment, glycemic control and complications in type 2 diabetes in general practices (Disease Analyzer, Germany: 2008-2016).","authors":"Rathmann, Wolfgang; Scheerer, Markus; Rohwedder, Katja; Busch, Stefan; Kostev, Karel","year":2018,"journal":"Postgraduate medicine, 130(2), 244-250","doi":"10.1080/00325481.2018.1421842","pmid":"29291638","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03862","title":"What Is High Enough? Elevated NT-pro-BNP in Decompensated Paroxysmal Supraventricular Tachycardia.","authors":"Reeves, Shawn; Womack, Clayton; Lutherer, L O; Todd, Christopher; Pinkney, Kerrie; Kasemsri, Thivakorn","year":2018,"journal":"Journal of pediatric intensive care, 7(1), 49-53","doi":"10.1055/s-0037-1603760","pmid":"31073468","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03863","title":"Cholecystokinin secretion is suppressed by glucagon-like peptide-1: clue to the mechanism of the adverse gallbladder events of GLP-1-derived drugs.","authors":"Rehfeld, Jens F; Knop, Filip K; Asmar, Ali; Madsbad, Sten; Holst, Jens J; Asmar, Meena","year":2018,"journal":"Scandinavian journal of gastroenterology, 53(12), 1429-1432","doi":"10.1080/00365521.2018.1530297","pmid":"30449207","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03864","title":"The Origin and Understanding of the Incretin Concept.","authors":"Rehfeld, Jens F","year":2018,"journal":"Frontiers in endocrinology, 9, 387","doi":"10.3389/fendo.2018.00387","pmid":"30061863","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03865","title":"Gastrointestinal distribution of chicken gastrin-cholecystokinin family transcript expression and response to short-term nutritive state.","authors":"Reid, Angus M A; Dunn, Ian C","year":2018,"journal":"General and comparative endocrinology, 255, 64-70","doi":"10.1016/j.ygcen.2017.10.009","pmid":"29061367","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03866","title":"Biological profiling of plasma neuropeptide Y in relation to posttraumatic stress symptoms in two combat cohorts.","authors":"Reijnen, Alieke; Geuze, Elbert; Eekhout, Iris; Maihofer, Adam X; Nievergelt, Caroline M; Baker, Dewleen G; Vermetten, Eric","year":2018,"journal":"Biological psychology, 134, 72-79","doi":"10.1016/j.biopsycho.2018.02.008","pmid":"29471015","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across two large prospective cohorts (N=892 and N=2,427), three distinct plasma NPY (pNPY) trajectories were identified from measurements taken before and shortly after military deployment. However, in both cohorts:\n\n- pNPY trajectories were not related to the level of PTSD symptoms over time\n- Pre-deployment pNPY levels alone did not predict PTSD development\n\nThis challenges previous smaller studies that suggested high NPY levels might serve as a resilience biomarker. The current findings suggest limited usefulness of peripherally measured NPY (blood levels) for predicting PTSD risk, though central nervous system NPY levels might still be relevant.","whyItMatters":"The military desperately needs biomarkers that can identify soldiers at risk for PTSD before they deploy, enabling targeted prevention. NPY was a promising candidate based on smaller studies showing that Special Forces soldiers (known for resilience) had higher NPY levels. This large, well-designed study's null finding is important — it redirects the search for PTSD biomarkers away from peripheral NPY and suggests that the relationship between NPY and stress resilience may be more complex than previously thought, potentially involving brain-specific rather than blood-based measurements.","specificNumbers":"","methodology":"Two longitudinal prospective cohort studies of military personnel were analyzed. Data collection began before deployment, with follow-up assessments completed up to two years after deployment. Plasma NPY levels were measured before and shortly after deployment using standard assays. PTSD symptoms were assessed at multiple time points using validated instruments. Three distinct NPY trajectories were identified using latent trajectory modeling. The relationship between NPY trajectories and PTSD symptom development was examined in both cohorts.","limitations":"Only peripheral (blood) NPY was measured, which may not reflect central nervous system NPY activity relevant to stress processing. The cohorts were predominantly male military personnel, limiting generalizability. PTSD symptoms were self-reported rather than clinician-diagnosed. The timing and frequency of NPY measurements may not capture dynamic stress-related NPY changes. Different assay methods between cohorts could introduce variability."},{"rthcId":"RPEP-03867","title":"Capromorelin: a ghrelin receptor agonist and novel therapy for stimulation of appetite in dogs.","authors":"Rhodes, Linda; Zollers, Bill; Wofford, Jessica A; Heinen, Ernst","year":2018,"journal":"Veterinary medicine and science, 4(1), 3-16","doi":"10.1002/vms3.83","pmid":"29468076","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03868","title":"The potential of substance P to initiate and perpetuate cortical spreading depression (CSD) in rat in vivo.","authors":"Richter, Frank; Eitner, Annett; Leuchtweis, Johannes; Bauer, Reinhard; Ebersberger, Andrea; Lehmenkühler, Alfred; Schaible, Hans-Georg","year":2018,"journal":"Scientific reports, 8(1), 17656","doi":"10.1038/s41598-018-36330-2","pmid":"30518958","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03869","title":"Acute administration of capsaicin increases resting energy expenditure in young obese subjects without affecting energy intake, appetite, and circulating levels of orexigenic/anorexigenic peptides.","authors":"Rigamonti, Antonello E; Casnici, Claudia; Marelli, Ornella; De Col, Alessandra; Tamini, Sofia; Lucchetti, Elisa; Tringali, Gabriella; De Micheli, Roberta; Abbruzzese, Laura; Bortolotti, Mauro; Cella, Silvano G; Sartorio, Alessandro","year":2018,"journal":"Nutrition research (New York, N.Y.), 52, 71-79","doi":"10.1016/j.nutres.2018.02.002","pmid":"29530622","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03870","title":"Glucagon like peptide-2 and neoplasia; a systematic review.","authors":"Ring, Linea Landgrebe; Nerup, Nikolaj; Jeppesen, Palle Bekker; Svendsen, Lars Bo; Achiam, Michael Patrick","year":2018,"journal":"Expert review of gastroenterology & hepatology, 12(3), 257-264","doi":"10.1080/17474124.2018.1417032","pmid":"29231791","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03871","title":"Efficacy of designer K11 antimicrobial peptide (a hybrid of melittin, cecropin A1 and magainin 2) against Acinetobacter baumannii-infected wounds.","authors":"Rishi, Praveen; Vashist, Tanvi; Sharma, Avantika; Kaur, Amrita; Kaur, Arashdeep; Kaur, Navneet; Kaur, Indu Pal; Tewari, Rupinder","year":2018,"journal":"Pathogens and disease, 76(7)","doi":"10.1093/femspd/fty072","pmid":"30184071","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03872","title":"Constrained α-Helical Peptides as Inhibitors of Protein-Protein and Protein-DNA Interactions.","authors":"Roy, Siddhartha; Ghosh, Piya; Ahmed, Israr; Chakraborty, Madhumita; Naiya, Gitashri; Ghosh, Basusree","year":2018,"journal":"Biomedicines, 6(4)","doi":"10.3390/biomedicines6040118","pmid":"30567318","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03873","title":"Anti-emetic Action of the Brain-Penetrating New Ghrelin Agonist, HM01, Alone and in Combination With the 5-HT3 Antagonist, Palonosetron and With the NK1 Antagonist, Netupitant, Against Cisplatin- and Motion-Induced Emesis in Suncus murinus (House Musk Shrew).","authors":"Rudd, John A; Chan, Sze W; Ngan, Man P; Tu, Longlong; Lu, Zengbing; Giuliano, Claudio; Lovati, Emanuela; Pietra, Claudio","year":2018,"journal":"Frontiers in pharmacology, 9, 869","doi":"10.3389/fphar.2018.00869","pmid":"30127745","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"HM01, an orally bioavailable ghrelin receptor (GHS-R1A) agonist that penetrates the brain, reduced emesis induced by cisplatin (30 mg/kg) and motion (1 Hz horizontal displacement) in Suncus murinus at doses of 1–30 mg/kg given orally.\n\nImportantly, HM01 at just 3 mg/kg enhanced the anti-emetic effects of palonosetron alone and the palonosetron plus netupitant combination. However, HM01 was ineffective against emesis caused by nicotine or copper sulfate, indicating its anti-emetic action is selective to certain pathways. HM01 also improved food and water intake in animals treated with cisplatin or nicotine.","whyItMatters":"Chemotherapy-induced nausea and vomiting remains one of the most distressing side effects of cancer treatment, and current anti-emetic regimens don't fully control it in all patients. This study suggests that targeting the ghrelin pathway — a system primarily known for appetite regulation — could offer a new complementary approach. An oral, brain-penetrating ghrelin agonist that enhances existing anti-emetics could improve quality of life for chemotherapy patients while also addressing the appetite loss that commonly accompanies treatment.","specificNumbers":"","methodology":"Researchers used Suncus murinus (house musk shrews), an established animal model for studying vomiting since rodents cannot vomit. Animals were given HM01 orally at various doses (1–30 mg/kg) before being exposed to different emetic triggers: cisplatin injection, motion stimulation, nicotine injection, or copper sulfate gavage. Vomiting episodes were counted over observation periods, and food and water consumption were also measured. Combination experiments tested HM01 alongside standard anti-emetics palonosetron and netupitant.","limitations":"This study was conducted in house musk shrews, not humans, so the results may not directly translate to clinical settings. The specific doses and drug interactions could differ significantly in people. The study also did not measure nausea directly (only vomiting episodes), and nausea is often the more persistent and harder-to-treat symptom. Additionally, long-term safety of repeated ghrelin agonist use and potential metabolic side effects like appetite changes were not assessed."},{"rthcId":"RPEP-03874","title":"Trypanothione reductase inhibition and anti-leishmanial activity of all-hydrocarbon stapled α-helical peptides with improved proteolytic stability.","authors":"Ruiz-Santaquiteria, Marta; de Castro, Sonia; Toro, Miguel A; de Lucio, Héctor; Gutiérrez, Kilian Jesús; Sánchez-Murcia, Pedro A; Jiménez, María Ángeles; Gago, Federico; Jiménez-Ruiz, Antonio; Camarasa, María-José; Velázquez, Sonsoles","year":2018,"journal":"European journal of medicinal chemistry, 149, 238-247","doi":"10.1016/j.ejmech.2018.02.071","pmid":"29501944","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03875","title":"Intranasal oxytocin decreases cross-frequency coupling of neural oscillations at rest.","authors":"Rutherford, Helena J V; Guo, Xiaoyue M; Wu, Jia; Graber, Kelsey M; Hayes, Nathan J; Pelphrey, Kevin A; Mayes, Linda C","year":2018,"journal":"International journal of psychophysiology : official journal of the International Organization of Psychophysiology, 123, 143-151","doi":"10.1016/j.ijpsycho.2017.09.017","pmid":"28965930","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03876","title":"Single step recombinant human growth hormone (rhGH) purification from milk by peptide affinity chromatography.","authors":"Saavedra, Soledad L; Martínez Ceron, María C; Giudicessi, Silvana L; Forno, Guillermina; Bosco, María Belén; Marani, Mariela M; Erra-Balsells, Rosa; Albericio, Fernando; Cascone, Osvaldo; Camperi, Silvia A","year":2018,"journal":"Biotechnology progress, 34(4), 999-1005","doi":"10.1002/btpr.2645","pmid":"29693323","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03877","title":"Potential of Intranasal Neuropeptide Y (NPY) and/or Melanocortin 4 Receptor (MC4R) Antagonists for Preventing or Treating PTSD.","authors":"Sabban, Esther L; Serova, Lidia I","year":2018,"journal":"Military medicine, 183(suppl_1), 408-412","doi":"10.1093/milmed/usx228","pmid":"29635611","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03878","title":"A Cyclic Peptide Inhibitor of the iNOS-SPSB Protein-Protein Interaction as a Potential Anti-Infective Agent.","authors":"Sadek, Maiada M; Barlow, Nicholas; Leung, Eleanor W W; Williams-Noonan, Billy J; Yap, Beow Keat; Shariff, Fairolniza Mohd; Caradoc-Davies, Tom T; Nicholson, Sandra E; Chalmers, David K; Thompson, Philip E; Law, Ruby H P; Norton, Raymond S","year":2018,"journal":"ACS chemical biology, 13(10), 2930-2938","doi":"10.1021/acschembio.8b00561","pmid":"30226743","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03879","title":"Antioxidative and antibacterial peptides derived from bovine milk proteins.","authors":"Sah, B N P; Vasiljevic, T; McKechnie, S; Donkor, O N","year":2018,"journal":"Critical reviews in food science and nutrition, 58(5), 726-740","doi":"10.1080/10408398.2016.1217825","pmid":"27558592","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03880","title":"Importance of Net Hydrophobicity in the Cellular Uptake of All-Hydrocarbon Stapled Peptides.","authors":"Sakagami, Koki; Masuda, Toshihiro; Kawano, Kenichi; Futaki, Shiroh","year":2018,"journal":"Molecular pharmaceutics, 15(3), 1332-1340","doi":"10.1021/acs.molpharmaceut.7b01130","pmid":"29420899","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03881","title":"Elevated α-defensin levels in plasma and bronchoalveolar lavage fluid from patients with myositis-associated interstitial lung disease.","authors":"Sakamoto, Noriho; Ishimoto, Hiroshi; Kakugawa, Tomoyuki; Satoh, Minoru; Hasegawa, Tomoko; Tanaka, Shin; Hara, Atsuko; Nakashima, Shota; Yura, Hirokazu; Miyamura, Takuto; Koyama, Hanako; Morita, Towako; Nakamichi, Seiko; Obase, Yasushi; Ishimatsu, Yuji; Mukae, Hiroshi","year":2018,"journal":"BMC pulmonary medicine, 18(1), 44","doi":"10.1186/s12890-018-0609-5","pmid":"29530007","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Alpha-defensin (HNP 1-3) levels were significantly elevated in both plasma and bronchoalveolar lavage fluid (BALF) of myositis-associated ILD patients compared to healthy controls. Plasma HNP levels correlated with total cell counts in BALF. BALF HNP levels positively correlated with serum surfactant protein-A and the percentage of neutrophils in lung fluid.\n\nIn patients positive for anti-aminoacyl-tRNA synthetase (anti-ARS) antibodies, BALF HNP levels also correlated with the percentage of reticular opacities on high-resolution CT scans. However, survival did not differ between patients with higher and lower HNP levels.","whyItMatters":"Myositis-associated ILD is a serious condition with limited prognostic tools. If alpha-defensins can serve as biomarkers for disease activity, they could help doctors monitor lung involvement and guide treatment decisions. This also supports the broader concept that neutrophil-derived antimicrobial peptides play roles beyond infection control — they participate in autoimmune inflammation.","specificNumbers":"","methodology":"This was a case-control study comparing 56 patients with myositis-associated ILD to 24 healthy controls. HNP (alpha-defensin 1-3) levels were measured in plasma and bronchoalveolar lavage fluid using ELISA. Results were correlated with other disease markers including serum surfactant protein-A, BALF cell counts, and high-resolution CT findings.","limitations":"The sample size was relatively small (56 patients). Survival was not significantly different between high and low HNP groups, limiting the prognostic value. The study is observational and cannot determine whether elevated defensins cause lung damage or are simply a marker of neutrophilic inflammation. Further studies are needed to confirm clinical utility."},{"rthcId":"RPEP-03882","title":"Nose-to-brain peptide delivery - The potential of nanotechnology.","authors":"Samaridou, Eleni; Alonso, Maria José","year":2018,"journal":"Bioorganic & medicinal chemistry, 26(10), 2888-2905","doi":"10.1016/j.bmc.2017.11.001","pmid":"29170026","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03883","title":"Effect of Fish Collagen Hydrolysates on Type I Collagen mRNA Levels of Human Dermal Fibroblast Culture.","authors":"Sanchez, Ana; Blanco, Maria; Correa, Begoña; Perez-Martin, Ricardo I; Sotelo, Carmen G","year":2018,"journal":"Marine drugs, 16(5)","doi":"10.3390/md16050144","pmid":"29701725","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03884","title":"Macrocyclic α helical peptide therapeutic modality: A perspective of learnings and challenges.","authors":"Sawyer, Tomi K; Partridge, Anthony W; Kaan, Hung Yi Kristal; Juang, Yu-Chi; Lim, Shuhui; Johannes, Charles; Yuen, Tsz Ying; Verma, Chandra; Kannan, Srinivasaraghavan; Aronica, Pietro; Tan, Yaw Sing; Sherborne, Brad; Ha, Sookhee; Hochman, Jerome; Chen, Shiying; Surdi, Laura; Peier, Andrea; Sauvagnat, Berengere; Dandliker, Peter J; Brown, Christopher J; Ng, Simon; Ferrer, Fernando; Lane, David P","year":2018,"journal":"Bioorganic & medicinal chemistry, 26(10), 2807-2815","doi":"10.1016/j.bmc.2018.03.008","pmid":"29598901","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03885","title":"A Randomized Dose-Ranging Study of Neuropeptide Y in Patients with Posttraumatic Stress Disorder.","authors":"Sayed, Sehrish; Van Dam, Nicholas T; Horn, Sarah R; Kautz, Marin M; Parides, Michael; Costi, Sara; Collins, Katherine A; Iacoviello, Brian; Iosifescu, Dan V; Mathé, Aleksander A; Southwick, Steven M; Feder, Adriana; Charney, Dennis S; Murrough, James W","year":2018,"journal":"The international journal of neuropsychopharmacology, 21(1), 3-11","doi":"10.1093/ijnp/pyx109","pmid":"29186416","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03886","title":"Perspectives on Endogenous Opioids in Birds.","authors":"Scanes, Colin G; Pierzchala-Koziec, Krystyna","year":2018,"journal":"Frontiers in physiology, 9, 1842","doi":"10.3389/fphys.2018.01842","pmid":"30622479","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03887","title":"Agonists of growth hormone-releasing hormone (GHRH) inhibit human experimental cancers in vivo by down-regulating receptors for GHRH.","authors":"Schally, Andrew V; Wang, Haibo; He, Jinlin; Cai, Renzhi; Sha, Wei; Popovics, Petra; Perez, Roberto; Vidaurre, Irving; Zhang, Xianyang","year":2018,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 115(47), 12028-12033","doi":"10.1073/pnas.1813375115","pmid":"30373845","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03888","title":"Effect of feeding a high-carbohydrate or a high-fat diet on subsequent food intake and blood concentration of satiety-related hormones in dogs.","authors":"Schauf, S; Salas-Mani, A; Torre, C; Jimenez, E; Latorre, M A; Castrillo, C","year":2018,"journal":"Journal of animal physiology and animal nutrition, 102(1), e21-e29","doi":"10.1111/jpn.12696","pmid":"28447374","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03889","title":"Oxyntomodulin analogue increases energy expenditure via the glucagon receptor.","authors":"Scott, R; Minnion, J; Tan, T; Bloom, S R","year":2018,"journal":"Peptides, 104, 70-77","doi":"10.1016/j.peptides.2018.04.008","pmid":"29680267","tags":["glp-1","gut-hormones"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"Using a sustained-release oxyntomodulin analogue (OX-SR) in rats, researchers definitively showed that the energy expenditure (calorie-burning) effect of oxyntomodulin occurs through the glucagon receptor, not the GLP-1 receptor. When the GLP-1 receptor was blocked with Exendin 9-39, OX-SR still increased oxygen consumption (energy burning). But when glucagon receptor activity was eliminated, the energy expenditure boost completely disappeared.\n\nThis resolves a key controversy about how oxyntomodulin works: its appetite-suppressing effects come mainly through GLP-1 receptor activation, while its calorie-burning effects require glucagon receptor activation. Both receptor activities are needed for optimal weight loss.","whyItMatters":"Oxyntomodulin is a natural gut hormone that activates both GLP-1 and glucagon receptors — making it a natural 'dual agonist.' This study is critical for drug design because it shows that the two receptors contribute different benefits: GLP-1 for appetite suppression, glucagon for increased energy expenditure. Drugs like survodutide and other GLP-1/glucagon dual agonists in development are designed based on this principle, and this study provides the mechanistic proof for why balancing both receptor activities matters.","specificNumbers":"Sustained-release OXM analogue (OX-SR) · Significant increase in energy expenditure · Glucagon receptor: essential for energy expenditure · GLP-1 receptor blockade: did not prevent energy increase · Indirect calorimetry measurement","methodology":"Animal study in rats using a sustained-release oxyntomodulin analogue (OX-SR). Energy expenditure was measured by indirect calorimetry (oxygen consumption). The GLP-1 receptor was blocked using Exendin 9-39 to test whether energy expenditure still occurred. Separately, glucagon receptor activity was eliminated to test whether it was required. This receptor-specific blocking approach allowed researchers to dissect which receptor drives each metabolic effect.","limitations":"Rat study — the receptor pharmacology may not translate identically to humans. The specific OX-SR analogue used is a research tool, not a clinical drug candidate. The study focused on energy expenditure and did not measure appetite or food intake effects in parallel. Glucagon receptor activation also carries risks (e.g., hepatic glucose output), which were not assessed in this short-term study."},{"rthcId":"RPEP-03890","title":"Natural molecules induce and synergize to boost expression of the human antimicrobial peptide β-defensin-3.","authors":"Sechet, Emmanuel; Telford, Erica; Bonamy, Clément; Sansonetti, Philippe J; Sperandio, Brice","year":2018,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 115(42), E9869-E9878","doi":"10.1073/pnas.1805298115","pmid":"30275324","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03891","title":"Future Perspectives on GLP-1 Receptor Agonists and GLP-1/glucagon Receptor Co-agonists in the Treatment of NAFLD.","authors":"Seghieri, Marta; Christensen, Alexander S; Andersen, Andreas; Solini, Anna; Knop, Filip K; Vilsbøll, Tina","year":2018,"journal":"Frontiers in endocrinology, 9, 649","doi":"10.3389/fendo.2018.00649","pmid":"30459715","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies multiple mechanisms by which GLP-1-based therapies could treat NAFLD:\n\n- GLP-1 receptor agonists reduce liver inflammation and fibrosis through direct and indirect mechanisms\n- GLP-1 RAs reduce body weight, improving NAFLD independently of direct liver effects\n- Glucagon receptor agonism increases lipid oxidation and thermogenesis\n- Glucagon receptor signaling is disrupted in NAFLD, suggesting a therapeutic target\n- Supra-physiological glucagon receptor agonism could represent a novel NAFLD treatment approach\n- Dual GLP-1/glucagon co-agonists combine appetite reduction with increased fat burning\n- No pharmacotherapy was approved for NAFLD at the time of writing","whyItMatters":"NAFLD/MASLD is now the most common liver disease globally, and it was long considered untreatable with drugs. This review was among the first to systematically outline how peptide-based therapies targeting both GLP-1 and glucagon receptors could address this unmet medical need. The predictions have been partially validated by subsequent trials of semaglutide and survodutide in NASH/MASLD.","specificNumbers":"","methodology":"Narrative review covering NAFLD pathophysiology, the roles of GLP-1 and glucagon in liver metabolism, currently available GLP-1 receptor agonists, and emerging dual GLP-1/glucagon co-agonists. The review synthesized preclinical and clinical evidence available through 2018.","limitations":"As a 2018 review, it predates the major clinical trial results for GLP-1 drugs in NAFLD/NASH (e.g., semaglutide NASH trials) and the approval of resmetirom. The dual GLP-1/glucagon co-agonist data was largely preclinical at the time. The review could not assess the relative contribution of weight loss versus direct hepatic effects of these drugs."},{"rthcId":"RPEP-03892","title":"Standardization of BNP and NT-proBNP Immunoassays in Light of the Diverse and Complex Nature of Circulating BNP-Related Peptides.","authors":"Semenov, Alexander G; Feygina, Evgeniya E","year":2018,"journal":"Advances in clinical chemistry, 85, 1-30","doi":"10.1016/bs.acc.2018.02.001","pmid":"29655458","tags":[],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Different commercial immunoassays for BNP and NT-proBNP produce markedly different results that are not comparable to each other. There is currently no certified reference material or standardized calibration approach for either biomarker, meaning that diagnostic cut-off values are method-dependent rather than universal.\n\nThe lack of equivalence stems partly from the complex nature of circulating BNP-related peptides — BNP exists in multiple forms in blood (precursors, fragments, glycosylated variants), and different assays detect different combinations of these forms.","whyItMatters":"BNP and NT-proBNP blood tests are used millions of times yearly to diagnose heart failure, guide treatment decisions, and assess prognosis. If different lab instruments give different numbers for the same blood sample, doctors may misinterpret results — especially when patients switch hospitals or labs. Standardizing these peptide measurements is essential for consistent cardiac care worldwide.","specificNumbers":"BNP discovered in 1988 · Multiple commercial assays with non-comparable results · No certified reference material exists · No standardized calibration procedures","methodology":"This is a review chapter in Advances in Clinical Chemistry that synthesizes data on the molecular forms of circulating BNP-related peptides, compares the specificity and performance of existing commercial BNP and NT-proBNP immunoassays, and evaluates potential approaches for standardization including reference materials and measurement procedures.","limitations":"As a review, this paper does not present new experimental data. The standardization solutions discussed are proposals rather than implemented systems. The review was published in 2018 and the standardization landscape may have evolved since."},{"rthcId":"RPEP-03893","title":"A patent review on PD-1/PD-L1 antagonists: small molecules, peptides, and macrocycles (2015-2018).","authors":"Shaabani, Shabnam; Huizinga, Harmen P S; Butera, Roberto; Kouchi, Ariana; Guzik, Katarzyna; Magiera-Mularz, Katarzyna; Holak, Tad A; Dömling, Alexander","year":2018,"journal":"Expert opinion on therapeutic patents, 28(9), 665-678","doi":"10.1080/13543776.2018.1512706","pmid":"30107136","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03894","title":"Native Oxyntomodulin Has Significant Glucoregulatory Effects Independent of Weight Loss in Obese Humans With and Without Type 2 Diabetes.","authors":"Shankar, Sudha S; Shankar, R Ravi; Mixson, Lori A; Miller, Deborah L; Pramanik, Barnali; O'Dowd, Amy K; Williams, Donna M; Frederick, Clay B; Beals, Chan R; Stoch, S Aubrey; Steinberg, Helmut O; Kelley, David E","year":2018,"journal":"Diabetes, 67(6), 1105-1112","doi":"10.2337/db17-1331","pmid":"29545266","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03895","title":"Innervation Changes Induced by Inflammation in the Murine Vagina.","authors":"Sharma, Harman; Ji, Esther; Yap, Pauline; Vilimas, Pat; Kyloh, Melinda; Spencer, Nicholas J; Haberberger, Rainer V; Barry, Christine M","year":2018,"journal":"Neuroscience, 372, 16-26","doi":"10.1016/j.neuroscience.2017.12.026","pmid":"29294338","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03896","title":"Peptide and peptide-carbon nanotube hydrogels as scaffolds for tissue & 3D tumor engineering.","authors":"Sheikholeslam, Mohammadali; Wheeler, Scott D; Duke, Keely G; Marsden, Mungo; Pritzker, Mark; Chen, P","year":2018,"journal":"Acta biomaterialia, 69, 107-119","doi":"10.1016/j.actbio.2017.12.012","pmid":"29248638","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03897","title":"Generation of a novel long-acting thymosin alpha1-Fc fusion protein and its efficacy for the inhibition of breast cancer in vivo.","authors":"Shen, Xutong; Li, Qingqing; Wang, Fanwen; Bao, Jingxiao; Dai, Mengting; Zheng, Heng; Lao, Xingzhen","year":2018,"journal":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 108, 610-617","doi":"10.1016/j.biopha.2018.09.064","pmid":"30243095","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03898","title":"LC/MS/MS Bioanalysis of Protein-Drug Conjugates-The Importance of Incorporating Succinimide Hydrolysis Products.","authors":"Shi, Chuan; Goldberg, Shalom; Lin, Tricia; Dudkin, Vadim; Widdison, Wayne; Harris, Luke; Wilhelm, Sharon; Jmeian, Yazen; Davis, Darryl; O'Neil, Karyn; Weng, Naidong; Jian, Wenying","year":2018,"journal":"Analytical chemistry, 90(8), 5314-5321","doi":"10.1021/acs.analchem.8b00411","pmid":"29589741","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03899","title":"Efficacy and Safety of Once-Weekly Semaglutide for the Treatment of Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.","authors":"Shi, Fang-Hong; Li, Hao; Cui, Min; Zhang, Zai-Li; Gu, Zhi-Chun; Liu, Xiao-Yan","year":2018,"journal":"Frontiers in pharmacology, 9, 576","doi":"10.3389/fphar.2018.00576","pmid":"29915538","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03900","title":"Deepened cellular/subcellular interface penetration and enhanced antitumor efficacy of cyclic peptidic ligand-decorated accelerating active targeted nanomedicines.","authors":"Shi, Nian-Qiu; Li, Yan; Zhang, Yong; Li, Zheng-Qiang; Qi, Xian-Rong","year":2018,"journal":"International journal of nanomedicine, 13, 5537-5559","doi":"10.2147/IJN.S172556","pmid":"30271146","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03901","title":"A Pilot Study for the Detection of Cyclic Prolyl-Hydroxyproline (Pro-Hyp) in Human Blood after Ingestion of Collagen Hydrolysate.","authors":"Shigemura, Yasutaka; Iwasaki, Yu; Tateno, Mana; Suzuki, Asahi; Kurokawa, Mihoko; Sato, Yoshio; Sato, Kenji","year":2018,"journal":"Nutrients, 10(10)","doi":"10.3390/nu10101356","pmid":"30248982","tags":["collagen-peptides"],"studyType":"pilot-study","evidenceStrength":"low-moderate","keyFinding":"A novel cyclic form of the collagen peptide Pro-Hyp was detected in human blood for the first time after ingestion of collagen hydrolysate. Cyclic Pro-Hyp peaked in plasma at 2 hours post-ingestion, reaching levels of 0.14–0.34 nmol/mL — approximately 5% of the linear Pro-Hyp concentration.\n\nIn cell culture experiments, cyclic Pro-Hyp at 7 nmol/mL significantly enhanced the growth rate of mouse skin fibroblasts on collagen gel more than the linear form, suggesting it may be more biologically active despite its lower concentration.","whyItMatters":"Collagen supplements are widely used for skin and joint health, but how they work after digestion has been unclear. This study identifies a previously unknown cyclic peptide form that appears in the bloodstream after taking collagen — and shows it stimulates skin cell growth more effectively than the well-known linear form. This could help explain why collagen supplements seem to benefit skin, even though the exact mechanisms have been debated.","specificNumbers":"cyclic Pro-Hyp peak at 2 hours · 0.14–0.34 nmol/mL plasma levels · ~5% of linear Pro-Hyp levels · 7 nmol/mL enhanced fibroblast growth · LC-MS detection","methodology":"Pilot study in human subjects who ingested collagen hydrolysate. Blood samples were collected at intervals and analyzed by liquid chromatography mass spectrometry (LC-MS) to detect and quantify cyclic Pro-Hyp levels. Cell culture experiments tested the effect of cyclic versus linear Pro-Hyp on mouse skin fibroblast growth on collagen gel.","limitations":"This is a pilot study with a small sample size. The cell culture work used mouse fibroblasts, not human cells. The plasma concentrations of cyclic Pro-Hyp were much lower than the concentration used in the cell culture experiments (7 nmol/mL), so it's unclear whether physiological levels would produce the same fibroblast-stimulating effect in living skin tissue."},{"rthcId":"RPEP-03902","title":"Cancer immunotherapy-targeted glypican-3 or neoantigens.","authors":"Shimizu, Yasuhiro; Suzuki, Toshihiro; Yoshikawa, Toshiaki; Tsuchiya, Nobuhiro; Sawada, Yu; Endo, Itaru; Nakatsura, Tetsuya","year":2018,"journal":"Cancer science, 109(3), 531-541","doi":"10.1111/cas.13485","pmid":"29285841","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Glypican-3 peptide vaccines successfully induced cancer-specific cytotoxic T lymphocytes (CTLs) in most patients across multiple clinical trials (five registered trials). The peptide showed extreme cancer specificity when restricted to HLA-A24 and HLA-A2 molecules. The review also found that neoantigen-based personalized immunotherapy shows potential for eliciting cancer regression, and both approaches may complement immune checkpoint inhibitors for patients who don't respond to checkpoint therapy alone.","whyItMatters":"Immune checkpoint inhibitors have transformed cancer treatment, but many patients don't respond. Peptide vaccines targeting glypican-3 or tumor-specific neoantigens offer complementary strategies that could fill this gap — especially for cancers like hepatocellular carcinoma where glypican-3 is highly expressed.","specificNumbers":"","methodology":"The authors summarized results from five clinical trials (registered in the UMIN Clinical Trials Registry) testing glypican-3 peptide vaccines in cancer patients. They also reviewed the current state of neoantigen-based personalized cancer immunotherapy, drawing on their own research program and published literature.","limitations":"The abstract does not provide specific response rates, survival data, or detailed outcomes from the clinical trials mentioned. As a review summarizing the authors' own work, it may present a favorable view of the results. The specific cancer types and patient populations across the five trials are not detailed in the abstract."},{"rthcId":"RPEP-03903","title":"Z-505 hydrochloride ameliorates chemotherapy-induced anorexia in rodents via activation of the ghrelin receptor, GHSR1a.","authors":"Shiomi, Yoshihiro; Ohira, Yuta; Yoshimura, Makoto; Ozaki, Tomoko; Takei, Mineo; Tanaka, Takao","year":2018,"journal":"European journal of pharmacology, 818, 148-157","doi":"10.1016/j.ejphar.2017.10.047","pmid":"29066414","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03904","title":"Antitumor effect of oral cancer vaccine with Bifidobacterium delivering WT1 protein to gut immune system is superior to WT1 peptide vaccine.","authors":"Shirakawa, Toshiro; Kitagawa, Koichi","year":2018,"journal":"Human vaccines & immunotherapeutics, 14(1), 159-162","doi":"10.1080/21645515.2017.1382787","pmid":"29048978","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03905","title":"Effect of Different Proteases on the Degree of Hydrolysis and Angiotensin I-Converting Enzyme-Inhibitory Activity in Goat and Cow Milk.","authors":"Shu, Guowei; Huang, Jie; Bao, Chunju; Meng, Jiangpeng; Chen, He; Cao, Jili","year":2018,"journal":"Biomolecules, 8(4)","doi":"10.3390/biom8040101","pmid":"30262795","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03906","title":"Serum neuropeptide concentrations in cows with intrapartum uterine torsion.","authors":"Sickinger, Marlene; Roth, Joachim; Failing, Klaus; Wehrend, Axel","year":2018,"journal":"Animal reproduction science, 196, 193-196","doi":"10.1016/j.anireprosci.2018.08.007","pmid":"30107933","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03907","title":"The Safety and Efficacy of Growth Hormone Secretagogues.","authors":"Sigalos, John T; Pastuszak, Alexander W","year":2018,"journal":"Sexual medicine reviews, 6(1), 45-53","doi":"10.1016/j.sxmr.2017.02.004","pmid":"28400207","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03908","title":"LFchimera protects HeLa cells from invasion by Yersinia spp. in vitro.","authors":"Sijbrandij, Tjitske; Ligtenberg, Antoon J; Nazmi, Kamran; van den Keijbus, Petra A M; Veerman, Enno C I; Bolscher, Jan G M; Bikker, Floris J","year":2018,"journal":"Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine, 31(6), 941-950","doi":"10.1007/s10534-018-0136-0","pmid":"30136243","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"LFchimera, a heterodimeric peptide construct combining the lactoferrampin and lactoferricin domains of bovine lactoferrin, inhibited host-cell invasion by both Yersinia enterocolitica and Yersinia pseudotuberculosis (Y. pestis simulants) in vitro.\n\nThe anti-invasion effect was host-cell mediated rather than bacteria-mediated — meaning the peptide altered the human cells' susceptibility to invasion rather than directly killing or disabling the bacteria. Additionally, co-exposure of HeLa epithelial cells to LFchimera and the bacterial strains triggered pro-inflammatory cytokine release, suggesting the peptide also stimulates the host immune response.","whyItMatters":"Plague remains a biosecurity concern and periodically causes outbreaks, while antibiotic resistance threatens current treatments. A peptide that protects host cells from bacterial invasion — rather than targeting the bacteria directly — represents a fundamentally different therapeutic approach that bacteria may not easily develop resistance to. Lactoferrin-derived peptides are also well-tolerated and derived from a natural human protein.","specificNumbers":"","methodology":"The study used human HeLa epithelial cells exposed to Y. enterocolitica and Y. pseudotuberculosis (used as safer surrogates for Y. pestis) in vitro. LFchimera was tested for its ability to inhibit bacterial adhesion to and invasion of host cells. The mechanism was dissected by determining whether the effect was on the bacteria or the host cells. Cytokine release from HeLa cells was measured to assess immune modulation.","limitations":"All experiments were conducted in vitro using HeLa cells, which may not fully represent the tissues infected during actual Yersinia infection (lymph nodes, lungs). Y. pestis itself was not tested (safer simulants were used), and there may be differences in virulence mechanisms. No in vivo animal model data were presented. The specific molecular mechanism by which LFchimera alters host cell susceptibility was not identified."},{"rthcId":"RPEP-03909","title":"Novel Cytoprotective Mediator, Stable Gastric Pentadecapeptide BPC 157. Vascular Recruitment and Gastrointestinal Tract Healing.","authors":"Sikiric, Predrag; Rucman, Rudolf; Turkovic, Branko; Sever, Marko; Klicek, Robert; Radic, Bozo; Drmic, Domagoj; Stupnisek, Mirjana; Misic, Marija; Vuletic, Lovorka Batelja; Pavlov, Katarina Horvat; Barisic, Ivan; Kokot, Antonio; Peklic, Marina; Strbe, Sanja; Blagaic, Alenka Boban; Tvrdeic, Ante; Rokotov, Dinko Stancic; Vrcic, Hrvoje; Staresinic, Mario; Seiwerth, Sven","year":2018,"journal":"Current pharmaceutical design, 24(18), 1990-2001","doi":"10.2174/1381612824666180608101119","pmid":"29879879","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BPC 157, a pentadecapeptide (15 amino acids) native to human gastric juice, demonstrated a three-part cytoprotective mechanism: (1) stomach cell protection, (2) endothelium (blood vessel lining) protection, and (3) active blood vessel function control. After perforating injuries, BPC 157 activated blood vessels to grow toward the defect. After vessel obstruction, it activated collateral vessels to bypass the blockage.\n\nThe peptide prevented and reversed thrombosis in both arterial and venous models, attenuated bleeding and low platelet counts after amputation, and counteracted the effects of both L-NAME and L-arginine on the nitric oxide system. It has already entered clinical trials for ulcerative colitis and multiple sclerosis.","whyItMatters":"BPC 157 extends the concept of 'cytoprotection' — originally limited to stomach lining protection — into a whole-body healing principle. Its ability to protect endothelium, redirect blood vessel growth toward injuries, activate collateral circulation around blockages, and influence thrombosis represents a remarkably broad therapeutic profile for a single peptide. The fact that it's native to human gastric juice and has advanced to clinical trials makes it one of the more intriguing peptides in translational development.","specificNumbers":"15 amino acid peptide · Native to human gastric juice · 3-part cytoprotective mechanism · Clinical trials for ulcerative colitis and multiple sclerosis · Thrombosis reversal in arterial and venous models","methodology":"This is a review article summarizing the authors' extensive body of research on BPC 157. It synthesizes findings from multiple preclinical animal studies examining BPC 157's effects on gastrointestinal healing, vascular protection, thrombosis, bleeding, and organ lesion repair. The review presents a conceptual framework (three-part cytoprotection) for understanding BPC 157's mechanism of action.","limitations":"The vast majority of evidence comes from animal studies conducted primarily by this single research group. The review is written by BPC 157's discoverers, introducing potential bias. While clinical trials are mentioned (ulcerative colitis, multiple sclerosis), published human efficacy data from these trials is not presented in this abstract. The broad range of claimed benefits across many organ systems is unusual and warrants independent replication. The mechanisms underlying BPC 157's diverse effects are not fully elucidated."},{"rthcId":"RPEP-03910","title":"NPY Induces Stress Resilience via Downregulation of Ih in Principal Neurons of Rat Basolateral Amygdala.","authors":"Silveira Villarroel, Heika; Bompolaki, Maria; Mackay, James P; Miranda Tapia, Ana Pamela; Michaelson, Sheldon D; Leitermann, Randy J; Marr, Robert A; Urban, Janice H; Colmers, William F","year":2018,"journal":"The Journal of neuroscience : the official journal of the Society for Neuroscience, 38(19), 4505-4520","doi":"10.1523/JNEUROSCI.3528-17.2018","pmid":"29650696","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03911","title":"Inulin fiber dose-dependently modulates energy balance, glucose tolerance, gut microbiota, hormones and diet preference in high-fat-fed male rats.","authors":"Singh, Arashdeep; Zapata, Rizaldy C; Pezeshki, Adel; Reidelberger, Roger D; Chelikani, Prasanth K","year":2018,"journal":"The Journal of nutritional biochemistry, 59, 142-152","doi":"10.1016/j.jnutbio.2018.05.017","pmid":"30005919","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Inulin dose-dependently decreased caloric intake and respiratory quotient; improved glucose tolerance; increased Bacteroidetes and Bifidobacterium while decreasing Clostridium clusters I and IV; increased butyryl-CoA:acetate CoA-transferase (butyrate production); upregulated PYY, CCK, and proglucagon gene transcripts in cecum and colon; and increased plasma PYY and GLP-1 concentrations. Critically, 25% inulin attenuated the reduction in energy expenditure seen with equivalent calorie restriction (pair-fed controls) and decreased adiposity — showing metabolic benefits independent of calorie restriction alone.","whyItMatters":"GLP-1 receptor agonists like semaglutide are transforming obesity treatment by mimicking gut satiety peptides. This study shows that a common dietary fiber can naturally increase production of these same peptides — GLP-1, PYY, and CCK — through the gut microbiome. Understanding how prebiotics modulate the gut-peptide-brain axis could lead to dietary strategies that complement or provide alternatives to expensive peptide-based medications for weight management.","specificNumbers":"","methodology":"Male Sprague-Dawley rats were randomized to six high-fat diet groups: control (0% inulin), 2.5%, 10%, 25% inulin, 25% cellulose, and pair-fed to the 25% inulin group for 21 days. Researchers measured food intake, energy expenditure, body composition, glucose tolerance, gut microbiota, cecal gene expression, and plasma hormone levels. A separate experiment assessed diet preference after training periods.","limitations":"This is a rat study, and the high inulin doses (up to 25% of diet) may not be practical or tolerable in humans due to gastrointestinal side effects. The 21-day duration is short for assessing long-term metabolic effects. Diet preference experiments showed that high-fiber diets were less preferred, which could limit compliance. The gut microbiome differences between rats and humans mean the specific microbial changes may not directly translate."},{"rthcId":"RPEP-03912","title":"Versatility of cell-penetrating peptides for intracellular delivery of siRNA.","authors":"Singh, Tejinder; Murthy, Akula S N; Yang, Hye-Jin; Im, Jungkyun","year":2018,"journal":"Drug delivery, 25(1), 1996-2006","doi":"10.1080/10717544.2018.1543366","pmid":"30799658","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03913","title":"Matrikines for therapeutic and biomedical applications.","authors":"Sivaraman, K; Shanthi, C","year":2018,"journal":"Life sciences, 214, 22-33","doi":"10.1016/j.lfs.2018.10.056","pmid":"30449450","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03914","title":"Cross-talk among oxytocin and arginine-vasopressin receptors: Relevance for basic and clinical studies of the brain and periphery.","authors":"Song, Zhimin; Albers, H Elliott","year":2018,"journal":"Frontiers in neuroendocrinology, 51, 14-24","doi":"10.1016/j.yfrne.2017.10.004","pmid":"29054552","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03915","title":"Structural modification of the tripeptide KPV by reductive \"glycoalkylation\" of the lysine residue.","authors":"Songok, Abigael C; Panta, Pradip; Doerrler, William T; Macnaughtan, Megan A; Taylor, Carol M","year":2018,"journal":"PloS one, 13(6), e0199686","doi":"10.1371/journal.pone.0199686","pmid":"29953505","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03916","title":"Immune monitoring and TCR sequencing of CD4 T cells in a long term responsive patient with metastasized pancreatic ductal carcinoma treated with individualized, neoepitope-derived multipeptide vaccines: a case report.","authors":"Sonntag, Katja; Hashimoto, Hisayoshi; Eyrich, Matthias; Menzel, Moritz; Schubach, Max; Döcker, Dennis; Battke, Florian; Courage, Carolina; Lambertz, Helmut; Handgretinger, Rupert; Biskup, Saskia; Schilbach, Karin","year":2018,"journal":"Journal of translational medicine, 16(1), 23","doi":"10.1186/s12967-018-1382-1","pmid":"29409514","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03917","title":"A historical perspective on the role of sensory nerves in neurogenic inflammation.","authors":"Sousa-Valente, João; Brain, Susan D","year":2018,"journal":"Seminars in immunopathology, 40(3), 229-236","doi":"10.1007/s00281-018-0673-1","pmid":"29616309","tags":["neuropeptides"],"studyType":"review","evidenceStrength":"review","keyFinding":"This historical review traces more than a century of research on how sensory nerves drive inflammation — a process called neurogenic inflammation. Sensory nerves don't just detect pain; they actively release peptides that dilate blood vessels and recruit immune cells.\n\nThe key neuropeptides identified as drivers of neurogenic inflammation include substance P (which causes vasodilation and plasma leakage) and CGRP (calcitonin gene-related peptide, a potent vasodilator). Sensory nerves also release anti-inflammatory peptides like endogenous opioids and somatostatin, showing the system has built-in brakes. The discovery of TRP channels (particularly TRPV1) revealed how these nerves sense environmental stimuli like heat, chemicals, and injury — providing the molecular mechanism linking tissue damage to neuropeptide release and inflammation.","whyItMatters":"Neurogenic inflammation sits at the crossroads of pain and immune function, and the neuropeptides involved (substance P, CGRP, somatostatin) are now therapeutic targets. CGRP-blocking drugs have already revolutionized migraine treatment, and substance P antagonists are used for chemotherapy-induced nausea. Understanding this century-old field helps explain why peptide-based therapies targeting sensory nerve pathways are among the most promising approaches to inflammatory disease.","specificNumbers":"","methodology":"Narrative historical review covering research from the initial discovery of sensory nerve function through modern molecular characterization of neuropeptides and TRP channels. Synthesizes findings across vascular biology, pain research, and immunology.","limitations":"As a narrative review, this paper summarizes and interprets existing literature rather than presenting new data. The authors note that despite over a century of research, the precise role of sensory nerves in vascular inflammation versus pain processing remains unclear, highlighting gaps in the field."},{"rthcId":"RPEP-03918","title":"Lactobacillus casei BL23 modulates the innate immune response in Staphylococcus aureus-stimulated bovine mammary epithelial cells.","authors":"Souza, R F S; Rault, L; Seyffert, N; Azevedo, V; Le Loir, Y; Even, S","year":2018,"journal":"Beneficial microbes, 9(6), 985-995","doi":"10.3920/BM2018.0010","pmid":"30041534","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03919","title":"Truncation of neurokinin-1 receptor-Negative regulation of substance P signaling.","authors":"Spitsin, Sergei; Pappa, Vasiliki; Douglas, Steven D","year":2018,"journal":"Journal of leukocyte biology","doi":"10.1002/JLB.3MIR0817-348R","pmid":"29345372","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03920","title":"Future Pharmacotherapy for Obesity: New Anti-obesity Drugs on the Horizon.","authors":"Srivastava, Gitanjali; Apovian, Caroline","year":2018,"journal":"Current obesity reports, 7(2), 147-161","doi":"10.1007/s13679-018-0300-4","pmid":"29504049","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies several categories of peptide-based anti-obesity drugs in development:\n\n- **GLP-1 analogs**: Semaglutide (injectable and oral forms) leading the field\n- **Amylin mimetics**: Davalintide and dual amylin/calcitonin receptor agonists (DACRAs)\n- **Dual agonists**: GLP-1/glucagon receptor agonists (oxyntomodulin analogs)\n- **Triple agonists**: Tri-agonist 1706 targeting GLP-1, GIP, and glucagon receptors simultaneously\n- **Other peptide targets**: Peptide YY, setmelanotide (melanocortin receptor), neuropeptide Y antagonists (velneperit), leptin analogs (pramlintide-metreleptin combination)\n- **Anti-obesity vaccines**: Targeting ghrelin and somatostatin\n\nThe pipeline reflects growing understanding that obesity involves multiple neurohormonal pathways, and that targeting several simultaneously may produce superior weight loss.","whyItMatters":"This review captures a pivotal moment in obesity pharmacology — many of the drugs discussed (particularly semaglutide) went on to transform the field. Understanding the breadth of peptide-based approaches in development provides context for the current obesity drug landscape and highlights next-generation therapies that may further improve on current options.","specificNumbers":"","methodology":"This is a narrative review surveying the anti-obesity drug development pipeline as of 2018. The authors reviewed clinical trial data, preclinical studies, and mechanistic research on drugs at various stages of development, organized by their mechanism of action and molecular targets.","limitations":"As a 2018 review, several of the drugs discussed have since either succeeded (semaglutide) or failed (beloranib was halted due to safety concerns) in development. The review could not predict which candidates would ultimately reach market approval. Some approaches discussed (anti-obesity vaccines, some dual agonists) remain in early development or have been deprioritized. The review also doesn't address long-term safety data that has since emerged for some of these agents."},{"rthcId":"RPEP-03921","title":"Cellular proteostasis: a new twist in the action of thymosin α1.","authors":"Stincardini, Claudia; Renga, Giorgia; Villella, Valeria; Pariano, Marilena; Oikonomou, Vasilis; Borghi, Monica; Bellet, Marina M; Sforna, Luigi; Costantini, Claudio; Goldstein, Allan L; Garaci, Enrico; Romani, Luigina","year":2018,"journal":"Expert opinion on biological therapy, 18(sup1), 43-48","doi":"10.1080/14712598.2018.1484103","pmid":"30063867","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Thymosin alpha 1 (Tα1) demonstrated a dual mechanism against cystic fibrosis (CF) in preclinical models: it both corrected the underlying CFTR protein defect and reduced the chronic hyperinflammation that drives progressive lung damage. Tα1 achieves this through activation of the indoleamine 2,3-dioxygenase (IDO) pathway, which promotes immune tolerance and breaks the cycle of chronic inflammation. This represents a single peptide that addresses two of CF's core problems simultaneously.","whyItMatters":"Cystic fibrosis treatment typically requires multiple drugs — one to fix the faulty CFTR protein and others to control inflammation. Thymosin alpha 1 is already approved in many countries for infections and immune deficiencies, making it an existing drug with a potential new application. Its ability to both correct the CFTR defect and dampen inflammation through a single mechanism could simplify CF treatment significantly.","specificNumbers":"","methodology":"Expert opinion and review article discussing preclinical data on thymosin alpha 1 in cystic fibrosis models, with mechanistic analysis of the IDO-mediated tolerogenic pathway.","limitations":"All CF-related evidence is preclinical — no human clinical trials for this indication have been reported. The mechanistic pathway described (IDO-mediated proteostasis correction) needs validation in CF patients. The review does not include specific efficacy measurements or dose-response data."},{"rthcId":"RPEP-03922","title":"β-Lactamase Tools for Establishing Cell Internalization and Cytosolic Delivery of Cell Penetrating Peptides.","authors":"Stone, Shane R; Heinrich, Tatjana; Juraja, Suzy M; Satiaputra, Jiulia N; Hall, Clinton M; Anastasas, Mark; Mills, Anna D; Chamberlain, Christopher A; Winslow, Scott; Priebatsch, Kristin; Cunningham, Paula T; Hoffmann, Katrin; Milech, Nadia","year":2018,"journal":"Biomolecules, 8(3)","doi":"10.3390/biom8030051","pmid":"29997382","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03923","title":"Visual systemizing preference in children with autism: A randomized controlled trial of intranasal oxytocin.","authors":"Strathearn, Lane; Kim, Sohye; Bastian, D Anthony; Jung, Jennifer; Iyengar, Udita; Martinez, Sheila; Goin-Kochel, Robin P; Fonagy, Peter","year":2018,"journal":"Development and psychopathology, 30(2), 511-521","doi":"10.1017/S0954579417001018","pmid":"28712371","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03924","title":"Differential expression of intestinal nutrient transporters and host defense peptides in Eimeria maxima-infected Fayoumi and Ross chickens.","authors":"Su, S; Miska, K B; Fetterer, R H; Jenkins, M C; Lamont, S J; Wong, E A","year":2018,"journal":"Poultry science, 97(12), 4392-4400","doi":"10.3382/ps/pey286","pmid":"30007365","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03925","title":"Increased expression of IL-33 in rosacea skin and UVB-irradiated and LL-37-treated HaCaT cells.","authors":"Suhng, Eunah; Kim, Bo Hee; Choi, You Won; Choi, Hae Young; Cho, Hyunjin; Byun, Ji Yeon","year":2018,"journal":"Experimental dermatology, 27(9), 1023-1029","doi":"10.1111/exd.13702","pmid":"29873850","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03926","title":"Antibacterial Activity and Mechanism of Action of Bovine Lactoferricin Derivatives with Symmetrical Amino Acid Sequences.","authors":"Sun, Changbao; Li, Yingying; Cao, Songsong; Wang, Haimei; Jiang, Chenggang; Pang, Shiyue; Hussain, Muhammad Altaf; Hou, Juncai","year":2018,"journal":"International journal of molecular sciences, 19(10)","doi":"10.3390/ijms19102951","pmid":"30262770","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Four symmetrical peptide variants of lactoferricin B(18-28) (KCRRWQWRMKK) were engineered:\n- **KW-WK** (KWRRWQWRRWK): enhanced antibacterial activity, safe\n- **FP-PF** (FPRRWQWRRPF): enhanced antibacterial activity, safe\n- **KK-KK** (KKRRWQWRRKK): enhanced antibacterial activity, safe\n- **FW-WF** (FWRRWQWRRWF): enhanced antibacterial activity, but hemolytic (toxic to red blood cells)\n\nAll four peptides showed significantly greater antibacterial activity than the original LFcinB(18-28), demonstrating that symmetrical amino acid sequences enhance antimicrobial potency. The peptides killed bacteria by disrupting membrane integrity through cationic and amphipathic interactions with anionic bacterial membranes.","whyItMatters":"Designing effective antimicrobial peptides has been largely trial-and-error. This study introduces a rational design principle — symmetry — that consistently enhanced antibacterial activity across four different peptide variants. This provides peptide engineers with a new tool for creating more potent antimicrobial drugs from natural peptide templates, potentially accelerating the development of alternatives to failing conventional antibiotics.","specificNumbers":"","methodology":"Researchers modified an 11-residue lactoferricin B fragment by substituting amino acids to create symmetrical sequences while maintaining the cationic core. Antibacterial activity was tested against E. coli, Salmonella, and Staphylococcus. Mechanism of action was investigated through membrane integrity and permeabilization assays. Safety was assessed by hemolytic activity testing. Structural characteristics (charge, amphipathicity) were analyzed.","limitations":"The study tested antibacterial activity in vitro only — no animal infection models were used. One of four designed peptides (FW-WF) was hemolytic, demonstrating that symmetry alone doesn't guarantee safety. The study tested a limited number of bacterial species. Stability of the engineered peptides in biological fluids (blood, wound environment) was not assessed. The mechanism of membrane disruption is described at a general level without detailed structural studies of peptide-membrane interactions."},{"rthcId":"RPEP-03927","title":"The Regulation of Peripheral Metabolism by Gut-Derived Hormones.","authors":"Sun, Emily W L; Martin, Alyce M; Young, Richard L; Keating, Damien J","year":2018,"journal":"Frontiers in endocrinology, 9, 754","doi":"10.3389/fendo.2018.00754","pmid":"30662430","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03928","title":"Hydrogen sulfide modulates gastric acid secretion in rats via involvement of substance P and nuclear factor-κB signaling.","authors":"Sun, H-Z; Gong, X-Y; Wu, L; Wang, X-X; Nie, Y-N; Shang, R; Wang, H; Li, Y-C; Sun, Q-F; Gao, P-F; Bi, J-X","year":2018,"journal":"Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 69(3)","doi":"10.26402/jpp.2018.3.08","pmid":"30279305","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03929","title":"Antimicrobial peptide expression in swine granulosa cells in response to lipopolysaccharide.","authors":"Sun, Xiaofeng; Xiu, Fangming; Pan, Bo; Li, Yapeng; Haskins, James T; Shen, Wei; Li, Julang","year":2018,"journal":"Theriogenology, 119, 80-90","doi":"10.1016/j.theriogenology.2018.06.011","pmid":"29982140","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03930","title":"Long-Term Outcomes of Elagolix in Women With Endometriosis: Results From Two Extension Studies.","authors":"Surrey, Eric; Taylor, Hugh S; Giudice, Linda; Lessey, Bruce A; Abrao, Mauricio S; Archer, David F; Diamond, Michael P; Johnson, Neil P; Watts, Nelson B; Gallagher, J Chris; Simon, James A; Carr, Bruce R; Dmowski, W Paul; Leyland, Nicholas; Singh, Sukhbir S; Rechberger, Tomasz; Agarwal, Sanjay K; Duan, W Rachel; Schwefel, Brittany; Thomas, James W; Peloso, Paul M; Ng, Juki; Soliman, Ahmed M; Chwalisz, Kristof","year":2018,"journal":"Obstetrics and gynecology, 132(1), 147-160","doi":"10.1097/AOG.0000000000002675","pmid":"29889764","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03931","title":"Enhancement of Self-Aggregation Properties of Linear Elastin-Derived Short Peptides by Simple Cyclization: Strong Self-Aggregation Properties of Cyclo[FPGVG] n, Consisting Only of Natural Amino Acids.","authors":"Suyama, Keitaro; Tatsubo, Daiki; Iwasaki, Wataru; Miyazaki, Masaya; Kiyota, Yuhei; Takahashi, Ichiro; Maeda, Iori; Nose, Takeru","year":2018,"journal":"Biomacromolecules, 19(8), 3201-3211","doi":"10.1021/acs.biomac.8b00353","pmid":"29932654","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03932","title":"A Novel Venom-Derived Peptide for Brachytherapy of Glioblastoma: Preclinical Studies in Mice.","authors":"Swenson, Steve; Minea, Radu O; Tuan, Cao Duc; Thein, Thu-Zan; Chen, Thomas C; Markland, Francis S","year":2018,"journal":"Molecules (Basel, Switzerland), 23(11)","doi":"10.3390/molecules23112918","pmid":"30413113","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03933","title":"Stealth Peptides Target Cellular Powerhouses to Fight Rare and Common Age-Related Diseases.","authors":"Szeto, Hazel H","year":2018,"journal":"Protein and peptide letters, 25(12), 1108-1123","doi":"10.2174/0929866525666181101105209","pmid":"30381054","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03934","title":"Evaluation of the hemocompatibility of RADA 16-I peptide.","authors":"Taghavi, Laleh; Aramvash, Asieh; Seyedkarimi, Mansooreh Sadat; Malek Sabet, Narges","year":2018,"journal":"Journal of biomaterials applications, 32(8), 1024-1031","doi":"10.1177/0885328217748861","pmid":"29249197","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03935","title":"A Recombinant Snake Cathelicidin Derivative Peptide: Antibiofilm Properties and Expression in Escherichia coli.","authors":"Tajbakhsh, Mercedeh; Akhavan, Maziar Mohammad; Fallah, Fatemeh; Karimi, Abdollah","year":2018,"journal":"Biomolecules, 8(4)","doi":"10.3390/biom8040118","pmid":"30360422","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Cath-A inhibited growth of A. baumannii clinical isolates from medical instruments at MIC values of 8-16 μg/mL. Against P. aeruginosa, MICs ranged from 16 to ≥256 μg/mL. The peptide significantly removed established biofilms of both species. Cath-A showed minimal hemolytic and cytotoxic activity against eukaryotic cells. Recombinant production in E. coli BL21 using pET-32a(+) vector with thioredoxin fusion yielded 17.6 mg/L of partially purified peptide with confirmed antimicrobial activity after enterokinase cleavage.","whyItMatters":"Hospital-acquired infections from drug-resistant bacteria like A. baumannii kill thousands of patients annually, and biofilm formation on medical devices makes these infections nearly impossible to treat with conventional antibiotics. Antimicrobial peptides represent a fundamentally different mechanism of killing bacteria that is harder for pathogens to develop resistance against, making Cath-A and similar peptides promising alternatives.","specificNumbers":"","methodology":"Researchers designed Cath-A, a 34-amino-acid derivative of cathelicidin-BF from snake venom. Antimicrobial activity was tested against A. baumannii and P. aeruginosa isolates from hospital medical instruments using standard MIC determination. Biofilm disruption was assessed on established biofilms. For production, the Cath-A gene was cloned into pET-32a(+) and expressed as a thioredoxin fusion protein in E. coli BL21. Purification used Ni2+ affinity chromatography followed by enterokinase cleavage to release the mature peptide.","limitations":"All testing was in vitro — no animal infection models were used. The P. aeruginosa MICs were highly variable (16 to ≥256 μg/mL), suggesting inconsistent activity against this pathogen. The peptide was only partially purified, and the 17.6 mg/L yield may need significant optimization for commercial production. Stability in biological fluids, pharmacokinetics, and in vivo toxicity were not assessed. The specific biofilm disruption mechanism was not elucidated."},{"rthcId":"RPEP-03936","title":"The antimicrobial potential of a new derivative of cathelicidin from Bungarus fasciatus against methicillin-resistant Staphylococcus aureus.","authors":"Tajbakhsh, Mercedeh; Karimi, Abdollah; Tohidpour, Abolghasem; Abbasi, Naser; Fallah, Fatemeh; Akhavan, Maziar Mohammad","year":2018,"journal":"Journal of microbiology (Seoul, Korea), 56(2), 128-137","doi":"10.1007/s12275-018-7444-5","pmid":"29392557","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03937","title":"Cathelicidin promotes inflammation by enabling binding of self-RNA to cell surface scavenger receptors.","authors":"Takahashi, Toshiya; Kulkarni, Nikhil Nitin; Lee, Ernest Y; Zhang, Ling-Juan; Wong, Gerard C L; Gallo, Richard L","year":2018,"journal":"Scientific reports, 8(1), 4032","doi":"10.1038/s41598-018-22409-3","pmid":"29507358","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03938","title":"Delivery of Oxytocin to the Brain for the Treatment of Autism Spectrum Disorder by Nasal Application.","authors":"Tanaka, Akiko; Furubayashi, Tomoyuki; Arai, Mari; Inoue, Daisuke; Kimura, Shunsuke; Kiriyama, Akiko; Kusamori, Kosuke; Katsumi, Hidemasa; Yutani, Reiko; Sakane, Toshiyasu; Yamamoto, Akira","year":2018,"journal":"Molecular pharmaceutics, 15(3), 1105-1111","doi":"10.1021/acs.molpharmaceut.7b00991","pmid":"29338251","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03939","title":"Expression and Purification of the Main Component Contained in Camel Milk and Its Antimicrobial Activities Against Bacterial Plant Pathogens.","authors":"Tanhaeian, Abbas; Shahriari Ahmadi, Farajollah; Sekhavati, Mohammad Hadi; Mamarabadi, Mojtaba","year":2018,"journal":"Probiotics and antimicrobial proteins, 10(4), 787-793","doi":"10.1007/s12602-018-9416-9","pmid":"29619665","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03940","title":"Effective cancer therapy based on selective drug delivery into cells across their membrane using receptor-mediated endocytosis.","authors":"Tashima, Toshihiko","year":2018,"journal":"Bioorganic & medicinal chemistry letters, 28(18), 3015-3024","doi":"10.1016/j.bmcl.2018.07.012","pmid":"30031619","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03941","title":"Antigens and Antibodies in Disease With Specifics About CGRP Immunology.","authors":"Taylor, Frederick R","year":2018,"journal":"Headache, 58 Suppl 3, 230-237","doi":"10.1111/head.13409","pmid":"30187471","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03942","title":"Anti-Calcitonin Gene-Related Peptide (CGRP) Therapies: Update on a Previous Review After the American Headache Society 60th Scientific Meeting, San Francisco, June 2018.","authors":"Tepper, Stewart J","year":2018,"journal":"Headache, 58 Suppl 3, 276-290","doi":"10.1111/head.13417","pmid":"30403405","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03943","title":"History and Review of anti-Calcitonin Gene-Related Peptide (CGRP) Therapies: From Translational Research to Treatment.","authors":"Tepper, Stewart J","year":2018,"journal":"Headache, 58 Suppl 3, 238-275","doi":"10.1111/head.13379","pmid":"30242830","tags":["cgrp"],"studyType":"review","evidenceStrength":"strong","keyFinding":"This comprehensive review traces the development of anti-CGRP therapies from the first proof-of-concept with olcegepant in 2004 to the FDA approval of erenumab in May 2018 — the first monoclonal antibody approved for migraine prevention. It summarizes randomized controlled trial data for four anti-CGRP monoclonal antibodies (erenumab, galcanezumab, fremanezumab, eptinezumab) and two small-molecule gepants (ubrogepant, rimegepant) for acute migraine treatment.\n\nGalcanezumab also showed effectiveness in preventing episodic cluster headache, expanding the potential uses of this drug class beyond migraine.","whyItMatters":"For decades, migraine patients relied on medications that were developed for other conditions (blood pressure drugs, antidepressants, anti-seizure drugs). Anti-CGRP therapies were the first treatments designed specifically for migraine based on understanding the biology of the disease. This review captures the moment that era began.","specificNumbers":"Erenumab FDA approved: May 17, 2018 · 4 monoclonal antibodies in development · 2 gepants completed pivotal trials · First gepant proof-of-concept: 2004","methodology":"Narrative review of the translational research pathway, pathophysiology, and all accessible randomized controlled trials, abstracts, platform presentations, and press releases on anti-CGRP monoclonal antibodies and gepants through May 2018.","limitations":"Written in May 2018, this review captures only the earliest clinical data. Several of the drugs discussed were still awaiting FDA decisions at the time of publication. Long-term safety and real-world effectiveness data were not yet available. As a single-author narrative review, it does not use systematic review methodology."},{"rthcId":"RPEP-03944","title":"Lateral septum growth hormone secretagogue receptor affects food intake and motivation for sucrose reinforcement.","authors":"Terrill, Sarah J; Wall, Kaylee D; Medina, Nelson D; Maske, Calyn B; Williams, Diana L","year":2018,"journal":"American journal of physiology. Regulatory, integrative and comparative physiology, 315(1), R76-R83","doi":"10.1152/ajpregu.00339.2017","pmid":"29590554","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03945","title":"Elevated levels of the antimicrobial peptide LL-37 in hidradenitis suppurativa are associated with a Th1/Th17 immune response.","authors":"Thomi, Rahel; Schlapbach, Christoph; Yawalkar, Nikhil; Simon, Dagmar; Yerly, Daniel; Hunger, Robert E","year":2018,"journal":"Experimental dermatology, 27(2), 172-177","doi":"10.1111/exd.13482","pmid":"29222824","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03946","title":"Stable gastric pentadecapeptide BPC 157 in honeybee (Apis mellifera) therapy, to control Nosema ceranae invasions in apiary conditions.","authors":"Tlak Gajger, I; Ribarić, J; Smodiš Škerl, M; Vlainić, J; Sikirić, P","year":2018,"journal":"Journal of veterinary pharmacology and therapeutics, 41(4), 614-621","doi":"10.1111/jvp.12509","pmid":"29682749","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03947","title":"Glucagon-like peptide 1 signaling inhibits allergen-induced lung IL-33 release and reduces group 2 innate lymphoid cell cytokine production in vivo.","authors":"Toki, Shinji; Goleniewska, Kasia; Reiss, Sara; Zhang, Jian; Bloodworth, Melissa H; Stier, Matthew T; Zhou, Weisong; Newcomb, Dawn C; Ware, Lorraine B; Stanwood, Gregg D; Galli, Aurelio; Boyd, Kelli L; Niswender, Kevin D; Peebles, R Stokes","year":2018,"journal":"The Journal of allergy and clinical immunology, 142(5), 1515-1528.e8","doi":"10.1016/j.jaci.2017.11.043","pmid":"29331643","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03948","title":"Females have stronger neurogenic response than males after non-specific nasal challenge in patients with seasonal allergic rhinitis.","authors":"Tomljenovic, Dejan; Baudoin, Tomislav; Megla, Zeljka Bukovec; Geber, Goran; Scadding, Glenis; Kalogjera, Livije","year":2018,"journal":"Medical hypotheses, 116, 114-118","doi":"10.1016/j.mehy.2018.04.021","pmid":"29857893","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03949","title":"Glycemic control of type 2 diabetes mellitus across stages of renal impairment: information for primary care providers.","authors":"Tong, Lili; Adler, Sharon","year":2018,"journal":"Postgraduate medicine, 130(4), 381-393","doi":"10.1080/00325481.2018.1457397","pmid":"29667921","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Traditional diabetes drugs (insulin, metformin, sulfonylureas, meglitinides) all require dose adjustments or carry heightened risks in kidney impairment. Among newer agents, GLP-1 receptor agonists liraglutide and semaglutide demonstrated reductions in adverse renal and cardiovascular events. DPP-4 inhibitors require dose adjustments except linagliptin. All SGLT2 inhibitors were contraindicated at very low kidney function (eGFR <30). Some DPP-4 inhibitors reduce albuminuria. The review emphasizes individualized therapy selection based on kidney function stage.","whyItMatters":"Diabetic kidney disease affects about 40% of people with type 2 diabetes and greatly increases the risk of death from heart disease. Choosing the right diabetes medication for these patients requires balancing blood sugar control with kidney safety. GLP-1 peptide drugs' dual benefit — glycemic control plus cardiovascular and kidney protection — makes them increasingly important for this large patient population.","specificNumbers":"","methodology":"Narrative clinical review for primary care providers, synthesizing prescribing guidelines, pharmacokinetic data, and clinical trial evidence across all stages of renal impairment for each major class of type 2 diabetes medication.","limitations":"Published in 2018, the review predates important kidney outcome trials (CREDENCE, DAPA-CKD, FLOW) that strengthened the evidence for SGLT2 inhibitors and GLP-1 agonists in CKD. Some recommendations about SGLT2 inhibitor kidney function thresholds have since been updated. The review covers all diabetes drug classes broadly, rather than providing deep analysis of any one class. Newer agents (tirzepatide, oral semaglutide) are not included."},{"rthcId":"RPEP-03950","title":"Quinolones Modulate Ghrelin Receptor Signaling: Potential for a Novel Small Molecule Scaffold in the Treatment of Cachexia.","authors":"Torres-Fuentes, Cristina; Pastor-Cavada, Elena; Cano, Rafael; Kandil, Dalia; Shanahan, Rachel; Juan, Rocio; Shaban, Hamdy; McGlacken, Gerard P; Schellekens, Harriët","year":2018,"journal":"International journal of molecular sciences, 19(6)","doi":"10.3390/ijms19061605","pmid":"29848961","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03951","title":"Facing the Challenges of Neuropeptide Gene Knockouts: Why Do They Not Inhibit Reproduction in Adult Teleost Fish?","authors":"Trudeau, Vance L","year":2018,"journal":"Frontiers in neuroscience, 12, 302","doi":"10.3389/fnins.2018.00302","pmid":"29773976","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03952","title":"Expression of α-Defensins, CD20+ B-lymphocytes, and Intraepithelial CD3+ T-lymphocytes in the Intestinal Mucosa of Patients with Liver Cirrhosis: Emerging Mediators of Intestinal Barrier Function.","authors":"Tsiaoussis, Georgios I; Papaioannou, Eleni C; Kourea, Eleni P; Assimakopoulos, Stelios F; Theocharis, Georgios I; Petropoulos, Michalis; Theopistos, Vasileios I; Diamantopoulou, Georgia G; Lygerou, Zoi; Spiliopoulou, Iris; Thomopoulos, Konstantinos C","year":2018,"journal":"Digestive diseases and sciences, 63(10), 2582-2592","doi":"10.1007/s10620-018-5146-9","pmid":"29876779","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Cirrhotic patients (n=67) showed diminished HD5 and HD6 expression compared to healthy controls (n=27; p=0.000287 and p=0.000314 respectively). Decompensated cirrhosis patients (n=40) had even lower defensin expression than compensated patients (n=27; p=0.025 and p=0.041). Cirrhotic patients had significantly higher serum endotoxin levels (p<0.0001).\n\nHD5 and HD6 expression showed strong inverse correlations with endotoxin levels (r=-0.790 and r=-0.777, both p<0.0001). Intraepithelial T-lymphocytes were decreased in decompensated cirrhosis versus controls (p=0.002), but B-lymphocyte infiltrates did not differ between groups.","whyItMatters":"Bacterial translocation (bacteria leaking from the gut into the bloodstream) is a major cause of infection and death in cirrhosis patients. Understanding that antimicrobial peptide depletion underlies this gut barrier failure opens new therapeutic avenues — potentially boosting defensin expression could prevent infections without relying solely on antibiotics, which risk resistance.","specificNumbers":"","methodology":"Prospective study of 40 patients with decompensated cirrhosis, 27 with compensated cirrhosis, and 27 healthy controls. All underwent duodenal biopsy. HD5 and HD6 expression in intestinal crypts was evaluated by immunohistochemistry and immunofluorescence. Serum endotoxin was quantified. Intraepithelial T-lymphocytes and lamina propria B-lymphocytes were counted.","limitations":"The study is cross-sectional, so it cannot determine whether defensin loss causes gut barrier dysfunction or results from it. The biopsy location (duodenum) may not represent the entire intestinal barrier. The mechanism by which cirrhosis reduces defensin expression was not investigated. Sample sizes, while reasonable, are modest for subgroup analyses."},{"rthcId":"RPEP-03953","title":"Involvement of the cystathionine-γ-lyase/Cav3.2 pathway in substance P-induced bladder pain in the mouse, a model for nonulcerative bladder pain syndrome.","authors":"Tsubota, Maho; Okawa, Yasumasa; Irie, Yuhei; Maeda, Mariko; Ozaki, Tomoka; Sekiguchi, Fumiko; Ishikura, Hiroyasu; Kawabata, Atsufumi","year":2018,"journal":"Neuropharmacology, 133, 254-263","doi":"10.1016/j.neuropharm.2018.01.037","pmid":"29407215","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03954","title":"Expression and Implication of Clusterin in Left Ventricular Remodeling After Myocardial Infarction.","authors":"Turkieh, Annie; Fertin, Marie; Bouvet, Marion; Mulder, Paul; Drobecq, Hervé; Lemesle, Gilles; Lamblin, Nicolas; de Groote, Pascal; Porouchani, Sina; Chwastyniak, Maggy; Beseme, Olivia; Amouyel, Philippe; Mouquet, Frédéric; Balligand, Jean-Luc; Richard, Vincent; Bauters, Christophe; Pinet, Florence","year":2018,"journal":"Circulation. Heart failure, 11(6), e004838","doi":"10.1161/CIRCHEARTFAILURE.117.004838","pmid":"29891738","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Proteomic analysis of 246 patients (REVE-2 study) identified increased plasma clusterin in patients with high left ventricular remodeling after first anterior MI. In rat MI models, cardiac clusterin expression increased and correlated with remodeling parameters.\n\nSilencing clusterin in hypertrophied cardiomyocytes decreased cell size, ANP and BNP expression, and ERK1/2 activity — establishing a prohypertrophic role. Both precursor (p-CLU) and mature (m-CLU) forms were increased in failing human hearts. Circulating clusterin was significantly higher in heart failure patients who died from cardiovascular causes during 3-year follow-up (n=99) compared to survivors (n=99).","whyItMatters":"Despite advances in treatment, predicting which patients will develop harmful heart remodeling after a heart attack remains a major clinical challenge. BNP is already the standard biomarker, but adding clusterin could improve prediction. More importantly, the discovery that clusterin actively promotes heart cell enlargement (alongside ANP/BNP upregulation) identifies a potential therapeutic target — blocking clusterin might prevent the remodeling that leads to heart failure.","specificNumbers":"","methodology":"Multi-level translational study: (1) proteomic biomarker discovery in 246 MI patients (REVE-2 cohort), (2) clusterin expression analysis in rat MI models, (3) functional studies using siRNA silencing in hypertrophied rat neonatal cardiomyocytes, (4) confirmation in failing human heart tissue, and (5) prognostic validation comparing plasma clusterin in 99 heart failure patients who died vs. 99 survivors over 3 years.","limitations":"The prognostic analysis used a matched case-control design (99 deaths vs. 99 survivors) rather than a full cohort analysis. Functional studies were performed in neonatal rat cardiomyocytes, which may not fully represent adult human cardiac biology. The precise mechanism by which clusterin promotes hypertrophy via ERK1/2 needs further elucidation. External validation in independent cohorts is needed before clinical implementation."},{"rthcId":"RPEP-03955","title":"Anti-Candidal Activity and Functional Mapping of Recombinant and Synthetic Neosartorya fischeri Antifungal Protein 2 (NFAP2).","authors":"Tóth, Liliána; Váradi, Györgyi; Borics, Attila; Batta, Gyula; Kele, Zoltán; Vendrinszky, Ákos; Tóth, Roberta; Ficze, Hargita; Tóth, Gábor K; Vágvölgyi, Csaba; Marx, Florentine; Galgóczy, László","year":2018,"journal":"Frontiers in microbiology, 9, 393","doi":"10.3389/fmicb.2018.00393","pmid":"29563903","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03956","title":"Transient receptor potential vanilloid 1 and transient receptor potential ankyrin 1 contribute to the progression of colonic inflammation in dextran sulfate sodium-induced colitis in mice: Links to calcitonin gene-related peptide and substance P.","authors":"Utsumi, Daichi; Matsumoto, Kenjiro; Tsukahara, Takuya; Amagase, Kikuko; Tominaga, Makoto; Kato, Shinichi","year":2018,"journal":"Journal of pharmacological sciences, 136(3), 121-132","doi":"10.1016/j.jphs.2017.12.012","pmid":"29478714","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03957","title":"Satiety and gastrointestinal hormones during a Mixed Meal Tolerance Test after gastric bypass surgery: association with plasma amino acid concentrations.","authors":"van den Broek, Merel; de Heide, Loek J M; Emous, Marloes; Wijma, Ragnhild B; Veeger, Nic J G M; Wolthuis, Albert; Laskewitz, Anke J; Heiner-Fokkema, M Rebecca; Muller Kobold, Anneke C; Wolffenbuttel, Bruce H R; van Beek, André P","year":2018,"journal":"Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery, 14(8), 1106-1117","doi":"10.1016/j.soard.2018.05.010","pmid":"29937240","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03958","title":"The potential for immunoglobulins and host defense peptides (HDPs) to reduce the use of antibiotics in animal production.","authors":"van Dijk, Albert; Hedegaard, Chris J; Haagsman, Henk P; Heegaard, Peter M H","year":2018,"journal":"Veterinary research, 49(1), 68","doi":"10.1186/s13567-018-0558-2","pmid":"30060758","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03959","title":"Human β-defensin-1: A natural antimicrobial peptide present in amniotic fluid that is increased in spontaneous preterm labor with intra-amniotic infection.","authors":"Varrey, Aneesha; Romero, Roberto; Panaitescu, Bogdan; Miller, Derek; Chaiworapongsa, Tinnakorn; Patwardhan, Manasi; Faro, Jonathan; Pacora, Percy; Hassan, Sonia S; Hsu, Chaur-Dong; Gomez-Lopez, Nardhy","year":2018,"journal":"American journal of reproductive immunology (New York, N.Y. : 1989), 80(4), e13031","doi":"10.1111/aji.13031","pmid":"30101464","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03960","title":"Effect of Polyvalence on the Antibacterial Activity of a Synthetic Peptide Derived from Bovine Lactoferricin against Healthcare-Associated Infectious Pathogens.","authors":"Vega Chaparro, Sandra C; Valencia Salguero, J Tatiana; Martínez Baquero, Diana A; Rosas Pérez, Jaiver E","year":2018,"journal":"BioMed research international, 2018, 5252891","doi":"10.1155/2018/5252891","pmid":"29984236","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03961","title":"Design, Synthesis and Evaluation of Branched RRWQWR-Based Peptides as Antibacterial Agents Against Clinically Relevant Gram-Positive and Gram-Negative Pathogens.","authors":"Vega, Sandra C; Martínez, Diana A; Chalá, María Del S; Vargas, Hernán A; Rosas, Jaiver E","year":2018,"journal":"Frontiers in microbiology, 9, 329","doi":"10.3389/fmicb.2018.00329","pmid":"29551999","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Three new antimicrobial peptides based on the RRWQWR motif from bovine lactoferricin B were designed as linear, dimeric, and tetrameric variants. All three outperformed the reference peptide against both ATCC reference strains and clinical isolates of Gram-positive and Gram-negative bacteria. MIC50 values ranged from 1.6-198.0 μM across different bacteria. However, the tetrameric peptide showed strong hemolytic activity (49.1% at 100 μM), limiting its therapeutic potential. SEM imaging confirmed that the branched designs expose the RRWQWR motif to pathogen surfaces.","whyItMatters":"As antibiotic resistance continues to grow, antimicrobial peptides offer an alternative approach. This study demonstrates that multiplying a key antimicrobial motif (RRWQWR) through branched peptide design enhances antibacterial potency against clinically relevant drug-resistant pathogens. The finding that branched architectures expose active motifs to bacterial surfaces provides a rational design principle for future AMP development.","specificNumbers":"3 new peptides · MIC50: 1.6-198.0 μM (reference strains) · MIC50: 1.6-75.0 μM (clinical isolates) · MBC: 12.5-200 μM · tetrameric hemolysis: 49.1% at 100 μM · tested against E. faecalis, P. aeruginosa, E. faecium, S. aureus, K. pneumoniae","methodology":"Three peptides containing one, two, or four copies of the RRWQWR motif were designed, synthesized, and screened against ATCC reference bacterial strains and clinical isolates of Gram-positive (E. faecalis, E. faecium, S. aureus) and Gram-negative (P. aeruginosa, K. pneumoniae) pathogens. Minimum inhibitory and bactericidal concentrations were determined. Hemolytic activity was measured to assess safety. Scanning electron microscopy visualized peptide-bacteria interactions.","limitations":"The tetrameric peptide's strong hemolytic activity (49.1%) makes it unsuitable for systemic use without modification. In vivo antibacterial efficacy was not tested. The mechanism of bacterial killing was not fully characterized beyond SEM imaging. Stability in biological fluids and serum was not assessed. The study did not test against the full panel of ESKAPE pathogens."},{"rthcId":"RPEP-03962","title":"Targeting glucose-dependent insulinotropic polypeptide receptor for neurodegenerative disorders.","authors":"Verma, Mahip K; Goel, Rajan; Krishnadas, Nandakumar; Nemmani, Kumar V S","year":2018,"journal":"Expert opinion on therapeutic targets, 22(7), 615-628","doi":"10.1080/14728222.2018.1487952","pmid":"29911915","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03963","title":"The NF-κB Inhibitor, IMD-0354, Affects Immune Gene Expression, Bacterial Microbiota and Trypanosoma cruzi Infection in Rhodnius prolixus Midgut.","authors":"Vieira, Cecilia S; Moreira, Otacílio C; Batista, Kate K S; Ratcliffe, Norman A; Castro, Daniele P; Azambuja, Patrícia","year":2018,"journal":"Frontiers in physiology, 9, 1189","doi":"10.3389/fphys.2018.01189","pmid":"30233391","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03964","title":"The Anti-Inflammatory Mediator, Vasoactive Intestinal Peptide, Modulates the Differentiation and Function of Th Subsets in Rheumatoid Arthritis.","authors":"Villanueva-Romero, Raúl; Gutiérrez-Cañas, Irene; Carrión, Mar; Pérez-García, Selene; Seoane, Iria V; Martínez, Carmen; Gomariz, Rosa P; Juarranz, Yasmina","year":2018,"journal":"Journal of immunology research, 2018, 6043710","doi":"10.1155/2018/6043710","pmid":"30155495","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03965","title":"Semaglutide, reduction in glycated haemoglobin and the risk of diabetic retinopathy.","authors":"Vilsbøll, Tina; Bain, Stephen C; Leiter, Lawrence A; Lingvay, Ildiko; Matthews, David; Simó, Rafael; Helmark, Ida Carøe; Wijayasinghe, Nelun; Larsen, Michael","year":2018,"journal":"Diabetes, obesity & metabolism, 20(4), 889-897","doi":"10.1111/dom.13172","pmid":"29178519","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03966","title":"Rat inferior caval vein (ICV) ligature and particular new insights with the stable gastric pentadecapeptide BPC 157.","authors":"Vukojević, Jakša; Siroglavić, Marko; Kašnik, Katarina; Kralj, Tamara; Stanćić, Duje; Kokot, Antonio; Kolarić, Darko; Drmić, Domagoj; Sever, Anita Zenko; Barišić, Ivan; Šuran, Jelena; Bojić, Davor; Patrlj, Masa Hrelec; Sjekavica, Ivica; Pavlov, Katarina Horvat; Vidović, Tinka; Vlainić, Josipa; Stupnišek, Mirjana; Seiwerth, Sven; Sikirić, Predrag","year":2018,"journal":"Vascular pharmacology, 106, 54-66","doi":"10.1016/j.vph.2018.02.010","pmid":"29510201","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BPC 157 administered at doses of 10 μg or 10 ng/kg counteracted virtually all consequences of inferior caval vein ligation in rats. Direct vein injury, thrombosis, thrombocytopenia, and prolonged bleeding were all counteracted. The peptide promoted rapid formation of collateral blood vessels and redistribution of trapped blood volume through alternative venous pathways.\n\nHemodynamic disturbances including venous hypertension, arterial hypotension, and tachycardia were counteracted. BPC 157-treated rats showed raised plasma nitric oxide values but normal MDA (oxidative stress marker) values. In vein tissue, the peptide reversed low NO values and counteracted elevated MDA levels. Gene expression changes were observed in EGR, NOS, SRF, VEGFR, and KRAS across multiple veins.","whyItMatters":"Venous thrombosis is a major clinical problem with limited treatment options beyond anticoagulants, which carry bleeding risks. This study suggests BPC 157 could address multiple aspects of venous disease simultaneously — thrombosis, vessel injury, hemodynamic disturbances, and oxidative stress — through a single peptide therapy, while also promoting the body's own compensatory mechanisms like collateral vessel formation.","specificNumbers":"","methodology":"Rats underwent inferior caval vein ligation up to the right ovarian vein to model Virchow's triad (vessel injury, stasis, thrombosis). BPC 157 was administered as either an early or delayed therapy regimen. Assessment included microcamera gross examination, microscopy, venography, bleeding time, blood pressure monitoring, ECG, thermography, plasma MDA and NO levels, tissue markers, and gene expression analysis via RT-PCR.","limitations":"This is an animal study in rats, and results may not translate to humans. BPC 157 is not approved for human use by any regulatory agency. The abstract does not provide specific statistical comparisons or group sizes. The study comes from the Sikirić group, which produces the majority of BPC 157 research, and independent replication by other laboratories would strengthen the findings. Specific mechanisms of action remain incompletely characterized."},{"rthcId":"RPEP-03967","title":"Development of the plant-derived peptide lunasin as an anticancer agent.","authors":"Vuyyuri, Saleha B; Shidal, Chris; Davis, Keith R","year":2018,"journal":"Current opinion in pharmacology, 41, 27-33","doi":"10.1016/j.coph.2018.04.006","pmid":"29679803","tags":[],"studyType":"Review","evidenceStrength":"preliminary","keyFinding":"Lunasin, a peptide naturally found in soybeans, has demonstrated both cancer-preventive (chemopreventive) and cancer-fighting (therapeutic) properties against multiple cancer types in preclinical studies. What makes lunasin unique is that it contains multiple functional domains that work through two distinct mechanisms: modifying gene expression by affecting histone acetylation (epigenetic regulation) and disrupting integrin signaling in cancer cells.\n\nRecent studies highlighted in this review show that lunasin's effects on integrin signaling in cancer stem cells are particularly noteworthy — it reduces the expression of stemness factors, which are the genes that allow cancer stem cells to maintain their aggressive, self-renewing properties. This leads to a reduction in metastatic potential, meaning the cancer becomes less likely to spread. The peptide's dual mechanism of action through both epigenetic and cell signaling pathways sets it apart from most single-target anticancer agents.","whyItMatters":"The link between soy consumption and reduced cancer risk has been observed in population studies for decades, but the specific compounds responsible have been debated. Lunasin represents a concrete molecular explanation — a bioactive peptide that can both prevent cancer initiation and fight existing tumors. Its ability to target cancer stem cells is especially significant because these cells drive metastasis and treatment resistance.","specificNumbers":"Lunasin = soy-derived peptide · Active against multiple cancer types · Dual mechanism: histone acetylation + integrin signaling · Reduces cancer stemness factors · Reduces metastatic potential","methodology":"Narrative review published in Current Opinion in Pharmacology, highlighting recent preclinical studies on lunasin's anticancer mechanisms, with emphasis on its effects on histone acetylation, integrin signaling, and cancer stem cell biology.","limitations":"All anticancer evidence for lunasin is preclinical — no human clinical trials for cancer treatment have been completed. The jump from soy-derived peptide activity in cell cultures and animal models to human therapeutic application is substantial. Bioavailability of dietary lunasin (from eating soy) versus purified lunasin delivery may differ significantly. Published in 2018, so some cited studies may have been superseded."},{"rthcId":"RPEP-03968","title":"Peptide-based Anxiolytics: The Molecular Aspects of Heptapeptide Selank Biological Activity.","authors":"Vyunova, Tatiana V; Andreeva, Lioudmila; Shevchenko, Konstantin; Myasoedov, Nikolay","year":2018,"journal":"Protein and peptide letters, 25(10), 914-923","doi":"10.2174/0929866525666180925144642","pmid":"30255741","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Selank acts as a positive allosteric modulator of GABA receptors, enhancing GABA binding in a concentration-dependent and subtype-selective manner. When combined with benzodiazepines like diazepam or the antipsychotic olanzapine, Selank's effects were not additive — instead, it blocked the modulatory activity of these drugs.\n\nThis indicates that Selank's binding site on the GABA receptor is distinct from the benzodiazepine binding site, though the sites may partially overlap. The non-cumulative interaction pattern suggests Selank modulates GABA signaling through a fundamentally different mechanism than conventional anxiolytics.","whyItMatters":"Anxiety disorders are the most common mental health problems globally, yet the main drugs used (benzodiazepines) cause dependence, cognitive impairment, and sedation. A peptide that targets the same GABA system but through a different mechanism — without these side effects — could represent a fundamentally better approach to anxiety treatment. This study provides the molecular evidence for how Selank achieves this.","specificNumbers":"","methodology":"The primary method was radioligand-receptor binding analysis using tritium-labeled GABA ([3H]GABA). Researchers isolated brain cell plasma membranes, measured protein concentrations, and assessed how Selank affected GABA binding alone and in combination with benzodiazepines and olanzapine. HPLC was used to verify reagent and Selank purity.","limitations":"This was an in vitro receptor binding study using rat brain membranes, not a clinical trial in humans. The study demonstrates a molecular mechanism but does not directly prove this mechanism is responsible for Selank's anti-anxiety effects in living organisms. The partial overlap of binding sites with benzodiazepines needs further structural characterization. Selank's effects on specific GABA receptor subtypes in different brain regions were not fully mapped."},{"rthcId":"RPEP-03969","title":"Oxytocin and Animal Models for Autism Spectrum Disorder.","authors":"Wagner, Shlomo; Harony-Nicolas, Hala","year":2018,"journal":"Current topics in behavioral neurosciences, 35, 213-237","doi":"10.1007/7854_2017_15","pmid":"28864977","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review examined both genetic and environmental animal models of ASD in which the oxytocin system was investigated. Key findings include evidence that the oxytocin system is perturbed in specific animal models of ASD, and that oxytocin administration can improve ASD-associated social behavior deficits in some of these models.\n\nCritically, the authors highlight that not all ASD subtypes involve oxytocin system disruption, and that the enormous heterogeneity of ASD may explain why clinical trials of oxytocin in humans have produced mixed results. They argue that perturbations in the oxytocin system should be investigated as potential stratifying biomarkers to identify which individuals are most likely to benefit from oxytocin treatment.","whyItMatters":"There are currently no approved drugs that treat the core social communication deficits of autism. Oxytocin has shown promise in some clinical trials but disappointing results in others. This review argues that the key to unlocking oxytocin's therapeutic potential may be identifying which specific subtypes of ASD involve a disrupted oxytocin system — a precision medicine approach that could transform how oxytocin is tested and used clinically.","specificNumbers":"","methodology":"This is a literature review examining published research on genetic- and environmental-based animal models for ASD. The authors surveyed studies that either investigated disruptions in the oxytocin system within these models or tested the effects of oxytocin administration on ASD-related behavioral phenotypes.","limitations":"As a review of animal studies, the findings have inherent limitations in translating to human ASD, which is far more heterogeneous and complex than any single animal model can capture. The review does not present new experimental data. The availability of validated biomarkers for oxytocin system perturbation in humans remains limited, making the proposed stratification approach challenging to implement clinically."},{"rthcId":"RPEP-03970","title":"Physiological Profile of Neuropeptide Y-Expressing Neurons in Bed Nucleus of Stria Terminalis in Mice: State of High Excitability.","authors":"Walter, Achim Leonhard; Bartsch, Julia Constance; Datunashvili, Maia; Blaesse, Peter; Lange, Maren Denise; Pape, Hans-Christian","year":2018,"journal":"Frontiers in cellular neuroscience, 12, 393","doi":"10.3389/fncel.2018.00393","pmid":"30455634","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03971","title":"Sensing of L-Arginine by Gut-Expressed Calcium Sensing Receptor Stimulates Gut Satiety Hormones Cholecystokinin and Glucose-Dependent Insulinotropic Peptide Secretion in Pig Model.","authors":"Wang, Chao; Kang, Cuicui; Xian, Yihan; Zhang, Mingyu; Chen, Xiaolin; Pei, Mingcai; Zhu, Weiyun; Hang, Suqin","year":2018,"journal":"Journal of food science, 83(9), 2394-2401","doi":"10.1111/1750-3841.14297","pmid":"30088839","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03972","title":"Immunomodulatory and enhanced antitumor activity of a modified thymosin α1 in melanoma and lung cancer.","authors":"Wang, Fanwen; Li, Bin; Fu, Pengcheng; Li, Qingqing; Zheng, Heng; Lao, Xingzhen","year":2018,"journal":"International journal of pharmaceutics, 547(1-2), 611-620","doi":"10.1016/j.ijpharm.2018.06.041","pmid":"29933059","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A modified version of thymosin alpha-1 (Tα1) fused with the tumor-homing peptide iRGD showed stronger antitumor activity than standard Tα1 against both melanoma and lung cancer in mice. The fusion peptide Tα1-iRGD promoted T-cell activation and increased CD86 expression on immune cells, accumulated more effectively in tumors, reduced tumor blood vessel density, and attached more readily to B16F10 melanoma and H460 lung cancer cells.\n\nThe modified peptide also demonstrated significantly better immunomodulatory activity in hydrocortisone-induced immunosuppression models, suggesting enhanced ability to boost immune function even under immunosuppressive conditions.","whyItMatters":"Thymosin alpha-1 is already used clinically as an immune-boosting peptide, but its effects are broad and non-specific. By fusing it with the tumor-homing peptide iRGD, researchers created a version that specifically targets tumors while retaining its immune-stimulating properties. This targeted approach could make thymosin alpha-1 more effective as a cancer therapy with potentially fewer off-target effects.","specificNumbers":"Tested against B16F10 melanoma and H460 lung cancer cells · Enhanced CD86 expression · Reduced tumor vessel density · Helical conformation in both Tα1 and Tα1-iRGD","methodology":"Researchers designed a fusion protein combining thymosin alpha-1 with the tumor-homing peptide iRGD. They tested it in multiple mouse models (BALB/c, C57BL, ICR, and nude mice) with melanoma and lung cancer tumors. They assessed T-cell activation, CD86 expression, tumor accumulation, tumor vessel density, cell attachment, and immunomodulatory activity in hydrocortisone-induced immunosuppression models. Circular dichroism spectroscopy was used to analyze protein structure.","limitations":"This was an animal study using mouse tumor models, and human efficacy remains untested. The specific dosing, treatment schedules, and long-term safety were not detailed in the abstract. The hydrocortisone immunosuppression model is a simplified representation of clinical immunosuppression."},{"rthcId":"RPEP-03973","title":"Thymosin Alpha1-Fc Modulates the Immune System and Down-regulates the Progression of Melanoma and Breast Cancer with a Prolonged Half-life.","authors":"Wang, Fanwen; Yu, Tingting; Zheng, Heng; Lao, Xingzhen","year":2018,"journal":"Scientific reports, 8(1), 12351","doi":"10.1038/s41598-018-30956-y","pmid":"30120362","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The Tα1-Fc fusion protein achieved a serum half-life of 25 hours in mice — approximately 13 times longer than native Tα1. Production yielded approximately 160.4 mg/L at greater than 90.3% purity. In tumor models, Tα1-Fc showed stronger antitumor activity than Tα1 in both 4T1 (breast cancer) and B16F10 (melanoma) xenograft models. The mechanism involved upregulation of CD86 expression (dendritic cell activation), increased secretion of IFN-γ and IL-2 (immune cytokines), and greater tumor infiltration by CD4+ and CD8+ T cells. The fusion protein also showed stronger activity in repairing immune injury by increasing lymphocyte counts.","whyItMatters":"Thymosin alpha-1 is already an approved drug in several countries for hepatitis B, hepatitis C, and as an immune adjuvant in cancer therapy. Its main limitation is the need for frequent dosing due to rapid clearance. A long-acting version with enhanced immune-boosting activity could make Tα1-based cancer immunotherapy more practical and more effective, potentially complementing checkpoint inhibitors and other immunotherapies.","specificNumbers":"","methodology":"Researchers used genetic engineering to construct a Tα1-Fc (IgG4 Fc domain) fusion protein expressed in E. coli. Production was optimized using single-factor experiments with lactose induction. Pharmacokinetics were measured in mouse serum. Immune repair was assessed in immunocompromised mice (hydrocortisone-treated). Antitumor activity was tested in 4T1 breast cancer and B16F10 melanoma xenograft models, with immune cell infiltration and cytokine profiles measured.","limitations":"This is a preclinical mouse study with xenograft tumor models, which may not accurately predict human responses. The Fc domain is from human IgG4, but the study was conducted in mice, raising questions about cross-species immune responses. No comparison with current standard immunotherapies (checkpoint inhibitors) was included. Long-term safety of the fusion protein was not assessed. The production was in E. coli, which doesn't glycosylate the Fc domain — this could affect function in humans."},{"rthcId":"RPEP-03974","title":"Inhibition of experimental small-cell and non-small-cell lung cancers by novel antagonists of growth hormone-releasing hormone.","authors":"Wang, Haibo; Zhang, Xianyang; Vidaurre, Irving; Cai, Renzhi; Sha, Wei; Schally, Andrew V","year":2018,"journal":"International journal of cancer, 142(11), 2394-2404","doi":"10.1002/ijc.31308","pmid":"29435973","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03975","title":"Cardiovascular safety of GLP-1 receptor agonists for diabetes patients with high cardiovascular risk: A meta-analysis of cardiovascular outcomes trials.","authors":"Wang, Qian; Liu, Lu; Gao, Ling; Li, Qiu","year":2018,"journal":"Diabetes research and clinical practice, 143, 34-42","doi":"10.1016/j.diabres.2018.06.009","pmid":"29935211","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03976","title":"Lipid-modified cell-penetrating peptide-based self-assembly micelles for co-delivery of narciclasine and siULK1 in hepatocellular carcinoma therapy.","authors":"Wang, Xiaoyun; Wu, Fengbo; Li, Guoyou; Zhang, Nan; Song, Xiangrong; Zheng, Yu; Gong, Changyang; Han, Bo; He, Gu","year":2018,"journal":"Acta biomaterialia, 74, 414-429","doi":"10.1016/j.actbio.2018.05.030","pmid":"29787814","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The lipid-modified cell-penetrating peptide micelles achieved multiple functional goals: they self-assembled to co-load both narciclasine (an AMPK activator) and siULK1 (an autophagy-blocking siRNA), showed pH-sensitive drug release favoring the acidic tumor microenvironment, and facilitated cellular uptake and endosome escape in HepG2 liver cancer cells.\n\nIn vitro, the combination treatment significantly increased apoptosis (programmed cell death) while declining autophagy through targeted regulation of the AMPK-ULK1 signaling axis. In vivo, the micelles efficiently reduced tumor growth in HCC xenograft models in mice with good safety profiles, confirming that simultaneously blocking autophagy while promoting cell death creates a synergistic anti-cancer effect.","whyItMatters":"Liver cancer is notoriously resistant to treatment, partly because tumor cells use autophagy as a survival strategy. By co-delivering a drug and a gene therapy in a single peptide-based vehicle, this approach attacks cancer from two directions simultaneously. The pH-sensitive release ensures the payloads activate mainly in tumor tissue, potentially reducing side effects. This demonstrates the versatility of cell-penetrating peptides as drug delivery platforms for combination cancer therapy.","specificNumbers":"","methodology":"A series of amphiphilic, lipid-modified cell-penetrating peptides were synthesized and characterized for self-assembly into micelles. The micelles were loaded with narciclasine and siULK1. In vitro studies in HepG2 cells assessed transfection efficiency, pH-sensitive drug/siRNA release, autophagy inhibition, and apoptosis induction. In vivo efficacy was tested in mice bearing HCC xenograft tumors, measuring tumor growth inhibition and safety.","limitations":"The in vivo study used a xenograft model (human cancer cells in immunodeficient mice), which does not replicate the full tumor microenvironment or immune interactions in human liver cancer. The specific peptide sequences and lipid modifications were not detailed in the abstract. Long-term toxicity was not assessed. Clinical translation of peptide-based micelle delivery systems faces manufacturing and stability challenges. Only one cancer cell line (HepG2) was used in vitro."},{"rthcId":"RPEP-03977","title":"Studies on the Use of Flagellin as an Immunostimulant and Vaccine Adjuvant in Fish Aquaculture.","authors":"Wangkahart, Eakapol; Secombes, Christopher J; Wang, Tiehui","year":2018,"journal":"Frontiers in immunology, 9, 3054","doi":"10.3389/fimmu.2018.03054","pmid":"30687309","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03978","title":"A Differential Innate Immune Response in Active and Chronic Stages of Bovine Infectious Digital Dermatitis.","authors":"Watts, Kaitlyn M; Fodor, Cristina; Beninger, Caroline; Lahiri, Priyoshi; Arrazuria, Rakel; De Buck, Jeroen; Knight, Cameron G; Orsel, Karin; Barkema, Herman W; Cobo, Eduardo R","year":2018,"journal":"Frontiers in microbiology, 9, 1586","doi":"10.3389/fmicb.2018.01586","pmid":"30072966","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03979","title":"Discovery of Peptidomimetic Antibody-Drug Conjugate Linkers with Enhanced Protease Specificity.","authors":"Wei, BinQing; Gunzner-Toste, Janet; Yao, Hui; Wang, Tao; Wang, Jing; Xu, Zijin; Chen, Jinhua; Wai, John; Nonomiya, Jim; Tsai, Siao Ping; Chuh, Josefa; Kozak, Katherine R; Liu, Yichin; Yu, Shang-Fan; Lau, Jeff; Li, Guangmin; Phillips, Gail D; Leipold, Doug; Kamath, Amrita; Su, Dian; Xu, Keyang; Eigenbrot, Charles; Steinbacher, Stefan; Ohri, Rachana; Raab, Helga; Staben, Leanna R; Zhao, Guiling; Flygare, John A; Pillow, Thomas H; Verma, Vishal; Masterson, Luke A; Howard, Philip W; Safina, Brian","year":2018,"journal":"Journal of medicinal chemistry, 61(3), 989-1000","doi":"10.1021/acs.jmedchem.7b01430","pmid":"29227683","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The researchers discovered that a cyclobutane-1,1-dicarboxamide-containing linker is hydrolyzed predominantly by cathepsin B, unlike the standard valine-citrulline dipeptide linker which is cleaved by multiple proteases. Key results:\n\n• The novel peptidomimetic linker showed enhanced protease specificity — preferentially cleaved by cathepsin B rather than multiple lysosomal enzymes\n• ADCs with the new linker were equally efficacious in vivo as those with the standard valine-citrulline dipeptide linker\n• Serum stability was maintained — the new linker did not break down prematurely in blood\n• Structure-guided design using crystallography informed the linker optimization\n• The approach opens a new chemical space beyond peptide-based linkers for controlling drug release selectivity","whyItMatters":"ADCs are one of the fastest-growing areas of cancer drug development, with three FDA-approved and over 60 in clinical trials at the time of this study. A major challenge is the therapeutic index — killing cancer cells while sparing healthy tissue. By making the linker more selective for tumor-specific enzymes, this technology could reduce the side effects of ADC therapies and expand the range of cancers that can be safely treated with these targeted drugs.","specificNumbers":"","methodology":"Using structure-guided drug design (including crystal structures of cathepsin B), researchers designed and synthesized novel non-peptide linkers based on a cyclobutane-1,1-dicarboxamide scaffold. They tested protease cleavage specificity in biochemical assays, measured serum stability, evaluated ADC efficacy in animal tumor models, and compared performance head-to-head against the standard valine-citrulline dipeptide linker used in FDA-approved ADCs.","limitations":"The study demonstrated proof of concept but did not include human clinical trials. While the new linker matched the standard linker's efficacy, the theoretical safety advantage of cathepsin B selectivity was not directly demonstrated through improved therapeutic index in the animal models shown. The long-term stability and immunogenicity of the peptidomimetic linker in humans is unknown."},{"rthcId":"RPEP-03980","title":"NUCB2/nesfatin-1: Expression and functions in the regulation of emotion and stress.","authors":"Wei, Yanyan; Li, Jiangbo; Wang, Huiling; Wang, Gaohua","year":2018,"journal":"Progress in neuro-psychopharmacology & biological psychiatry, 81, 221-227","doi":"10.1016/j.pnpbp.2017.09.024","pmid":"28963067","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03981","title":"A Novel Heat Shock Protein 70-based Vaccine Prepared from DC-Tumor Fusion Cells.","authors":"Weng, Desheng; Calderwood, Stuart K; Gong, Jianlin","year":2018,"journal":"Methods in molecular biology (Clifton, N.J.), 1709, 359-369","doi":"10.1007/978-1-4939-7477-1_26","pmid":"29177672","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03982","title":"Novel GLP-1/GLP-2 co-agonists display marked effects on gut volume and improves glycemic control in mice.","authors":"Wismann, Pernille; Pedersen, Søren L; Hansen, Gitte; Mannerstedt, Karin; Pedersen, Philip J; Jeppesen, Palle B; Vrang, Niels; Fosgerau, Keld; Jelsing, Jacob","year":2018,"journal":"Physiology & behavior, 192, 72-81","doi":"10.1016/j.physbeh.2018.03.004","pmid":"29540315","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03983","title":"Examination of the Clostridioides (Clostridium) difficile VanZ ortholog, CD1240.","authors":"Woods, Emily C; Wetzel, Daniela; Mukerjee, Monjori; McBride, Shonna M","year":2018,"journal":"Anaerobe, 53, 108-115","doi":"10.1016/j.anaerobe.2018.06.013","pmid":"29940245","tags":["antimicrobial-resistance","LL-37"],"studyType":"laboratory-study","evidenceStrength":"moderate","keyFinding":"Researchers identified a gene (vanZ1/CD1240) in C. difficile that contributes to low-level resistance against the antibiotic teicoplanin. When this gene was deleted, the bacteria became moderately more susceptible to teicoplanin. Restoring the gene restored resistance.\n\nAn unexpected finding: the antimicrobial peptide LL-37 (a human cathelicidin) triggered increased expression of the vanZ1 gene, even though VanZ1 itself didn't protect against LL-37. This suggests the bacterium may be using LL-37 as an environmental signal — detecting the human immune response and upregulating resistance factors in anticipation of antibiotic exposure.\n\nThe vanZ1 gene sits within a genetic element (the skin element) that is cut out during sporulation, meaning it is only active in vegetatively growing cells, not spores.","whyItMatters":"C. difficile is a leading cause of hospital-acquired diarrhea and kills thousands annually. Understanding how this pathogen resists antibiotics is critical for treatment. The discovery that the human antimicrobial peptide LL-37 induces expression of an antibiotic resistance gene reveals an unexpected connection between the innate immune response and bacterial resistance mechanisms — the bacterium may be eavesdropping on immune signals.","specificNumbers":"VanZ1 deletion = moderate decrease in teicoplanin resistance · LL-37 induced vanZ1 transcription · No effect on LL-37 resistance itself","methodology":"Researchers created a vanZ1 deletion mutant in C. difficile by exploiting the natural excision of the skin genetic element during sporulation. They tested resistance to teicoplanin and other antimicrobials, measured vanZ1 gene expression in response to various antimicrobials including LL-37, and performed complementation experiments using an inducible promoter to confirm VanZ1's role.","limitations":"The resistance conferred by VanZ1 is low-level and moderate, so its clinical significance is uncertain. The mechanism by which VanZ1 confers teicoplanin resistance remains undefined. The study is entirely in vitro — the relevance of LL-37-induced vanZ1 expression during actual human infection is unknown."},{"rthcId":"RPEP-03984","title":"How and why do gastrointestinal peptides influence food intake?","authors":"Woods, Stephen C; May-Zhang, Aaron A; Begg, Denovan P","year":2018,"journal":"Physiology & behavior, 193(Pt B), 218-222","doi":"10.1016/j.physbeh.2018.02.048","pmid":"29577941","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review presents three key lines of evidence that gut peptide satiation is learned rather than innate. First, the ability of some GI peptides to modify food intake depends on past experience and can be changed with new experience (malleable). Second, CCK and other 'satiation' signals that reduce food intake acutely may not continue to do so over repeated trials. Third, individuals only respond to a particular signal so long as it provides reliable information about caloric content.\n\nWhen a gut peptide becomes an unreliable predictor of calories (as happens with repeated exogenous administration), the individual shifts to relying on other signals to end meals. This learned association model explains why genetic knockouts and chronic peptide administration fail to produce sustained weight loss — the system compensates by using alternative satiety cues.","whyItMatters":"This review fundamentally challenges how we think about gut peptide-based obesity treatments. If CCK, GLP-1, and similar peptides work through learned associations rather than hardwired satiety circuits, it explains why chronic GLP-1 agonist treatment eventually plateaus and why weight regain occurs after discontinuation — the brain adapts. Understanding this could lead to more effective dosing strategies (perhaps intermittent rather than continuous) or combination approaches that prevent adaptive compensation.","specificNumbers":"","methodology":"This is a theoretical review synthesizing evidence from behavioral pharmacology, conditioning experiments, genetic knockout studies, and chronic peptide administration studies to propose a learning-based model of gut peptide satiation.","limitations":"As a theoretical review, it presents a provocative hypothesis without definitive proof that all gut peptide satiation is learned. The evidence cited is largely from animal studies, and human learning mechanisms around food intake may be more complex. The model may overstate the role of learning and understate hardwired satiety mechanisms — GLP-1 drugs do produce sustained (if plateauing) weight loss for many patients, suggesting some non-learned component. The review also doesn't address the metabolic effects of gut peptides (glucose lowering, etc.) that contribute to their clinical value independent of appetite."},{"rthcId":"RPEP-03985","title":"A stable meta-carborane enables the generation of boron-rich peptide agonists targeting the ghrelin receptor.","authors":"Worm, Dennis J; Els-Heindl, Sylvia; Kellert, Martin; Kuhnert, Robert; Saretz, Stefan; Koebberling, Johannes; Riedl, Bernd; Hey-Hawkins, Evamarie; Beck-Sickinger, Annette G","year":2018,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 24(10), e3119","doi":"10.1002/psc.3119","pmid":"30168238","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03986","title":"Mitochondrial-targeted penetrating peptide delivery for cancer therapy.","authors":"Wu, Jiao; Li, Jason; Wang, Hu; Liu, Chang-Bai","year":2018,"journal":"Expert opinion on drug delivery, 15(10), 951-964","doi":"10.1080/17425247.2018.1517750","pmid":"30173542","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03987","title":"A frog cathelicidin peptide effectively promotes cutaneous wound healing in mice.","authors":"Wu, Jing; Yang, Jun; Wang, Xiaofang; Wei, Lin; Mi, Kai; Shen, Yan; Liu, Tong; Yang, Hailong; Mu, Lixian","year":2018,"journal":"The Biochemical journal, 475(17), 2785-2799","doi":"10.1042/BCJ20180286","pmid":"30045878","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03988","title":"Antioxidant and anti-freezing peptides from salmon collagen hydrolysate prepared by bacterial extracellular protease.","authors":"Wu, RiBang; Wu, CuiLing; Liu, Dan; Yang, XingHao; Huang, JiaFeng; Zhang, Jiang; Liao, Binqiang; He, HaiLun","year":2018,"journal":"Food chemistry, 248, 346-352","doi":"10.1016/j.foodchem.2017.12.035","pmid":"29329864","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03989","title":"Targeting oncogenic transcriptional corepressor Nac1 POZ domain with conformationally constrained peptides by cyclization and stapling.","authors":"Wu, Tao; He, Ping; Wu, Wei; Chen, Yingli; Lv, Fenglin","year":2018,"journal":"Bioorganic chemistry, 80, 1-10","doi":"10.1016/j.bioorg.2018.05.024","pmid":"29864683","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03990","title":"Combination of entecavir with thymosin alpha-1 in HBV-related compensated cirrhosis: a prospective multicenter randomized open-label study.","authors":"Wu, Xiaoning; Shi, Yiwen; Zhou, Jialing; Sun, Yameng; Piao, Hongxin; Jiang, Wei; Ma, Anlin; Chen, Yongpeng; Xu, Mingyi; Xie, Wen; Cheng, Jun; Xie, Shibin; Shang, Jia; Cheng, Jilin; Xie, Qing; Ding, Huiguo; Zhang, Xuqing; Bai, Lang; Zhang, Mingxiang; Wang, Bingqiong; Chen, Shuyan; Ma, Hong; Ou, Xiaojuan; Jia, Jidong; You, Hong","year":2018,"journal":"Expert opinion on biological therapy, 18(sup1), 61-69","doi":"10.1080/14712598.2018.1451511","pmid":"30063860","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03991","title":"The Role of Apelin in Cardiovascular Diseases, Obesity and Cancer.","authors":"Wysocka, Marta B; Pietraszek-Gremplewicz, Katarzyna; Nowak, Dorota","year":2018,"journal":"Frontiers in physiology, 9, 557","doi":"10.3389/fphys.2018.00557","pmid":"29875677","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03992","title":"Improved anticancer efficacy of doxorubicin mediated by human-derived cell-penetrating peptide dNP2.","authors":"Xiang, Yucheng; Shan, Wei; Huang, Yuan","year":2018,"journal":"International journal of pharmaceutics, 551(1-2), 14-22","doi":"10.1016/j.ijpharm.2018.09.011","pmid":"30205127","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03993","title":"The Expression of Transcription Factors Mecp2 and CREB Is Modulated in Inflammatory Pelvic Pain.","authors":"Xie, Alison Xiaoqiao; Pan, Xiao-Qing; Meacham, Randall B; Malykhina, Anna P","year":2018,"journal":"Frontiers in systems neuroscience, 12, 69","doi":"10.3389/fnsys.2018.00069","pmid":"30687029","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03994","title":"Neuropeptide S Counteracts Paradoxical Sleep Deprivation-Induced Anxiety-Like Behavior and Sleep Disturbances.","authors":"Xie, Jun-Fan; Shao, Yu-Feng; Wang, Hai-Liang; Wang, Can; Cui, Guang-Fu; Kong, Xiang-Pan; Wang, Lin-Xin; Chen, Yu-Nong; Cong, Chao-Yu; Chen, Hai-Lin; Hou, Yi-Ping","year":2018,"journal":"Frontiers in cellular neuroscience, 12, 64","doi":"10.3389/fncel.2018.00064","pmid":"29559896","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03995","title":"Human Enteric α-Defensin 5 Promotes Shigella Infection by Enhancing Bacterial Adhesion and Invasion.","authors":"Xu, Dan; Liao, Chongbing; Zhang, Bing; Tolbert, W David; He, Wangxiao; Dai, Zhijun; Zhang, Wei; Yuan, Weirong; Pazgier, Marzena; Liu, Jiankang; Yu, Jun; Sansonetti, Philippe J; Bevins, Charles L; Shao, Yongping; Lu, Wuyuan","year":2018,"journal":"Immunity, 48(6), 1233-1244.e6","doi":"10.1016/j.immuni.2018.04.014","pmid":"29858013","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03996","title":"Macroporous silica nanoparticles for delivering Bcl2-function converting peptide to treat multidrug resistant-cancer cells.","authors":"Xu, Weixia; Ge, Pengjin; Niu, Boning; Zhang, Xiaokun; Liu, Jie; Xie, Jingjing","year":2018,"journal":"Journal of colloid and interface science, 527, 141-150","doi":"10.1016/j.jcis.2018.05.033","pmid":"29787950","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Macroporous silica nanoparticles with thiol surface modification achieved over 40% Bcl-2-converting peptide loading efficiency. The peptide penetrated into drug-resistant MCF7/DOX breast cancer cell mitochondria and bound Bcl-2, exposing its BH3 domain to convert it from pro-survival to pro-apoptotic. Different surface functionalities affected efficacy: amine-modified MSN surfaces caused the greatest cell apoptosis-inducing effect. This is the first demonstration of pore size and surface functionality-modulated silica nanoparticles for delivery of bio-macromolecules to treat multidrug resistant cancer.","whyItMatters":"Drug resistance is the leading cause of cancer treatment failure. Bcl-2 overexpression is a key resistance mechanism across many cancer types. A peptide that can turn this survival protein into an executioner — delivered efficiently by nanoparticles — could overcome resistance that makes cancers untreatable with conventional chemotherapy.","specificNumbers":"","methodology":"Macroporous silica nanoparticles were fabricated with various surface modifications (thiol, amine, and others). Peptide loading efficiency was measured. Intracellular delivery was tracked to confirm mitochondrial localization and Bcl-2 binding. Apoptosis was assessed in doxorubicin-resistant MCF7/DOX breast cancer cells.","limitations":"This is an in vitro study using a single drug-resistant breast cancer cell line (MCF7/DOX). No animal or human testing was performed. The long-term stability of the peptide-nanoparticle system, biodistribution, and potential toxicity in vivo are unknown. The approach has not been tested against other types of drug-resistant cancers."},{"rthcId":"RPEP-03997","title":"Substance P Attenuates Hypoxia/Reoxygenation-Induced Apoptosis via the Akt Signalling Pathway and the NK1-Receptor in H9C2Cells.","authors":"Xu, Ying; Gu, Qin; Tang, Jian; Qian, Yajun; Tan, Xiao; Yu, Zhuxi; Qu, Chen","year":2018,"journal":"Heart, lung & circulation, 27(12), 1498-1506","doi":"10.1016/j.hlc.2017.09.013","pmid":"29107510","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03998","title":"Hemolymph defensin from the hard tick Haemaphysalis longicornis attacks Gram-positive bacteria.","authors":"Yada, Yurika; Talactac, Melbourne Rio; Kusakisako, Kodai; Hernandez, Emmanuel Pacia; Galay, Remil Linggatong; Andoh, Masako; Fujisaki, Kozo; Tanaka, Tetsuya","year":2018,"journal":"Journal of invertebrate pathology, 156, 14-18","doi":"10.1016/j.jip.2018.07.005","pmid":"30003919","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-03999","title":"Codelivery of a cytotoxin and photosensitiser via a liposomal nanocarrier: a novel strategy for light-triggered cytosolic release.","authors":"Yaghini, Elnaz; Dondi, Ruggero; Edler, Karen J; Loizidou, Marilena; MacRobert, Alexander J; Eggleston, Ian M","year":2018,"journal":"Nanoscale, 10(43), 20366-20376","doi":"10.1039/c8nr04048f","pmid":"30376028","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04000","title":"Transcription factor specificity protein 1 modulates TGFβ1/Smad signaling to negatively regulate SIGIRR expression by human M1 macrophages stimulated with substance P.","authors":"Yamaguchi, Rui; Sakamoto, Arisa; Yamaguchi, Reona; Haraguchi, Misa; Narahara, Shinji; Sugiuchi, Hiroyuki; Yamaguchi, Yasuo","year":2018,"journal":"Cytokine, 108, 24-36","doi":"10.1016/j.cyto.2018.03.011","pmid":"29558695","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04001","title":"Exenatide once weekly for smoking cessation: study protocol for a randomized clinical trial.","authors":"Yammine, Luba; Kosten, Thomas R; Cinciripini, Paul M; Green, Charles E; Meininger, Janet C; Minnix, Jennifer A; Newton, Thomas F","year":2018,"journal":"Medicine, 97(2), e9567","doi":"10.1097/MD.0000000000009567","pmid":"29480848","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"This is a study protocol, not a results paper. The planned trial will randomize 90 prediabetic and/or overweight smokers 1:1 to exenatide extended-release or placebo, both combined with transdermal nicotine replacement therapy (NRT) and behavioral counseling.\n\nOutcomes include smoking abstinence (verified by expired CO ≤5 ppm), craving (Questionnaire of Smoking Urges), and withdrawal symptoms (Wisconsin Scale), assessed weekly during 6 weeks of treatment and at 1 and 4 weeks post-treatment. Cue-induced craving will be measured using virtual reality exposure at baseline and 3 weeks. The hypothesis is that exenatide will increase complete abstinence rates and reduce craving and withdrawal above standard NRT alone.","whyItMatters":"Smoking remains the leading preventable cause of death, and existing cessation medications have modest success rates. If GLP-1 drugs can reduce nicotine cravings and withdrawal through their effects on brain reward circuits, they could become a powerful new tool for smoking cessation — especially for the many smokers who are also overweight or prediabetic and could benefit from the metabolic effects simultaneously. This trial represents the first human test of this concept.","specificNumbers":"","methodology":"Double-blind, placebo-controlled, randomized clinical trial. Ninety treatment-seeking smokers who are prediabetic and/or overweight will be enrolled. Participants receive either exenatide once weekly or placebo, plus standard nicotine patches and behavioral counseling. Assessments occur weekly for 6 treatment weeks and at 1 and 4 weeks post-treatment. Virtual reality cue exposure is used to assess triggered cravings.","limitations":"As a protocol paper, no results are presented. The planned sample size of 90 is relatively small for a smoking cessation trial. Enrolling only overweight/prediabetic smokers limits generalizability to all smokers. Exenatide is an older GLP-1 RA with less potent effects than newer agents like semaglutide, so the results may underestimate the potential of the drug class. The 4-week post-treatment follow-up is short for assessing sustained abstinence."},{"rthcId":"RPEP-04002","title":"A defensin-like antimicrobial peptide from the manila clam Ruditapes philippinarum: Investigation of the antibacterial activities and mode of action.","authors":"Yang, Dinglong; Zhang, Qianqian; Wang, Qing; Chen, Lizhu; Liu, Yongliang; Cong, Ming; Wu, Huifeng; Li, Fei; Ji, Chenglong; Zhao, Jianmin","year":2018,"journal":"Fish & shellfish immunology, 80, 274-280","doi":"10.1016/j.fsi.2018.06.019","pmid":"29902560","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04003","title":"The effect of thymosin α1 for prevention of infection in patients with severe acute pancreatitis.","authors":"Yang, Na; Ke, Lu; Tong, Zhihui; Li, Weiqin","year":2018,"journal":"Expert opinion on biological therapy, 18(sup1), 53-60","doi":"10.1080/14712598.2018.1481207","pmid":"30063854","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Current infection prevention strategies for severe acute pancreatitis achieve limited success, likely because they fail to address the underlying immunosuppression that triggers infection. Thymosin α1, which has immune-cell-regulating properties, showed a prophylactic effect against SAP-related infection in clinical studies.\n\nThe review highlights that the immune suppression occurring in SAP's late phase is a key driver of infection risk, and that immunomodulatory therapies like thymosin α1 target this root cause rather than just treating infections after they occur. However, the evidence base remains at an early stage with limited sample sizes.","whyItMatters":"Infection remains the leading cause of death in severe acute pancreatitis, and existing preventive strategies are inadequate. Thymosin α1 addresses a critical gap by targeting the immune suppression that makes patients vulnerable to infection, rather than just trying to prevent pathogen exposure. If validated in larger trials, it could significantly reduce mortality in this devastating condition.","specificNumbers":"","methodology":"This is a narrative review examining currently available strategies for preventing infection in severe acute pancreatitis and the rationale and evidence for thymosin α1 use. The authors reviewed published clinical studies of thymosin α1 in SAP patients along with the broader literature on infection prevention in pancreatitis.","limitations":"This is a review article, not primary research. The clinical evidence for thymosin α1 in SAP is limited to early-stage studies with small sample sizes. No large, randomized, placebo-controlled trials are cited. The review does not provide specific outcome data or effect sizes. The optimal dosing, timing, and duration of thymosin α1 therapy for SAP infection prevention have not been established."},{"rthcId":"RPEP-04004","title":"Crystal structure of the human NK1 tachykinin receptor.","authors":"Yin, Jie; Chapman, Karen; Clark, Lindsay D; Shao, Zhenhua; Borek, Dominika; Xu, Qingping; Wang, Junmei; Rosenbaum, Daniel M","year":2018,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 115(52), 13264-13269","doi":"10.1073/pnas.1812717115","pmid":"30538204","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04005","title":"Elevated Inflammatory Plasma Biomarkers in Patients With Fabry Disease: A Critical Link to Heart Failure With Preserved Ejection Fraction.","authors":"Yogasundaram, Haran; Nikhanj, Anish; Putko, Brendan N; Boutin, Michel; Jain-Ghai, Shailly; Khan, Aneal; Auray-Blais, Christiane; West, Michael L; Oudit, Gavin Y","year":2018,"journal":"Journal of the American Heart Association, 7(21), e009098","doi":"10.1161/JAHA.118.009098","pmid":"30571380","tags":[],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"Patients with Fabry disease showed significantly elevated levels of multiple inflammatory and cardiac remodeling biomarkers compared to healthy controls, including the natriuretic peptides BNP and MR-pro ANP, matrix metalloproteases (MMP-2, MMP-9), TNF, TNFR1, TNFR2, IL-6, galectin-1, and globotriaosylsphingosine.\n\nKey biomarker correlations included: TNFR2, TNF, IL-6, MMP-2, and globotriaosylsphingosine were elevated in patients with left ventricular hypertrophy; BNP, MR-pro ANP, and MMP-2 correlated with diastolic dysfunction; and patients with cardiac scarring (late gadolinium enhancement on MRI) had higher BNP, MR-pro ANP, TNFR1, TNFR2, and MMP-2. These findings support a phenotype dominated by heart failure with preserved ejection fraction driven by systemic inflammation.","whyItMatters":"Fabry disease is a rare genetic condition that progressively damages the heart, kidneys, and nervous system. This study identifies a specific pattern of inflammatory and natriuretic peptide biomarkers that track with disease severity, potentially enabling better monitoring and earlier intervention. The connection to HFpEF pathophysiology through inflammation may also inform treatment strategies.","specificNumbers":"n=68 Fabry patients vs n=40 controls · 12 biomarkers measured · Multiple significant correlations with cardiac imaging · Multicenter cohort","methodology":"Multicenter observational study comparing plasma levels of 12 inflammatory and cardiac remodeling biomarkers between 68 Fabry disease patients and 40 healthy controls. Biomarker levels were correlated with clinical profile, cardiac MRI (including late gadolinium enhancement), and echocardiographic findings including diastolic function and left ventricular hypertrophy.","limitations":"Cross-sectional design cannot establish causation between inflammation and cardiac dysfunction. Relatively small sample size (68 patients) for a condition with heterogeneous presentation. The study cannot determine whether elevated biomarkers are causes or consequences of cardiac involvement in Fabry disease."},{"rthcId":"RPEP-04006","title":"Collagen peptides modulate the metabolism of extracellular matrix by human dermal fibroblasts derived from sun-protected and sun-exposed body sites.","authors":"Zague, Vivian; do Amaral, Jonatas Bussador; Rezende Teixeira, Paula; de Oliveira Niero, Evandro Luis; Lauand, Camila; Machado-Santelli, Glaucia Maria","year":2018,"journal":"Cell biology international, 42(1), 95-104","doi":"10.1002/cbin.10872","pmid":"28906033","tags":[],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Collagen hydrolysate (CH) — the collagen peptides found in supplements — increased procollagen I and collagen I content in human skin fibroblasts through a two-pronged mechanism: stimulating new collagen production while simultaneously inhibiting the enzymes (MMP-1 and MMP-2) that break collagen down. This worked in both standard cell cultures and a more realistic 3D human dermal equivalent model.\n\nImportantly, the effects were consistent regardless of whether fibroblasts came from sun-protected (chronologically aged) or sun-exposed (photoaged) skin. However, sun-exposed fibroblasts appeared more responsive — lower concentrations of collagen peptides were sufficient to stimulate them, suggesting photoaged skin cells may be more sensitive to the treatment.","whyItMatters":"Collagen supplements are a multi-billion dollar market, but the biological mechanism behind their clinical benefits has been poorly understood. This study provides concrete cellular evidence: collagen peptides don't just provide raw material — they actively signal skin cells to produce more collagen and simultaneously block the enzymes that destroy it. The finding that sun-damaged skin cells respond at lower doses is particularly relevant for anti-aging applications.","specificNumbers":"Increased procollagen I and collagen I content · Inhibited MMP-1 and MMP-2 activity · No effect on cell proliferation · Lower CH doses effective for sun-exposed cells · Confirmed in monolayer and 3D dermal equivalent models","methodology":"Human dermal fibroblasts were isolated from sun-protected (chronologically aged) and sun-exposed (photoaged) body sites. Cells were treated with collagen hydrolysate in both standard monolayer culture and a 3D human dermal equivalent model. Researchers measured procollagen I, collagen I, cell proliferation, and MMP-1/MMP-2 activity.","limitations":"This is an in vitro study — cells in a dish, not living skin. The collagen peptides were applied directly to cells, bypassing the digestive system that oral supplements must traverse. The abstract doesn't specify the source or molecular weight of the collagen hydrolysate, donor ages, or exact concentrations tested. The 3D model, while more realistic, still doesn't replicate the full complexity of aging skin with its blood supply, immune cells, and UV exposure."},{"rthcId":"RPEP-04007","title":"Gene cloning, expression and immune adjuvant properties of the recombinant fusion peptide Tα1-BLP on avian influenza inactivate virus vaccine.","authors":"Zhang, Cong; Zhou, Jiangfei; Cai, Kairui; Zhang, Wufan; Liao, Chengshui; Wang, Chen","year":2018,"journal":"Microbial pathogenesis, 120, 147-154","doi":"10.1016/j.micpath.2018.05.003","pmid":"29730515","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04008","title":"A Solid-Phase Approach to Accessing Bisthioether-Stapled Peptides Resulting in a Potent Inhibitor of PRC2 Catalytic Activity.","authors":"Zhang, Gan; Barragan, Flavia; Wilson, Khadija; Levy, Nissim; Herskovits, Adam; Sapozhnikov, Milana; Rodríguez, Yoel; Kelmendi, Leutrim; Alkasimi, Haleem; Korsmo, Hunter; Chowdhury, Maisha; Gerona-Navarro, Guillermo","year":2018,"journal":"Angewandte Chemie (International ed. in English), 57(52), 17073-17078","doi":"10.1002/anie.201810007","pmid":"30339297","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04009","title":"Peptidomimetics Targeting Protein-Protein Interactions for Therapeutic Development.","authors":"Zhang, Gan; Andersen, Jessica; Gerona-Navarro, Guillermo","year":2018,"journal":"Protein and peptide letters, 25(12), 1076-1089","doi":"10.2174/0929866525666181101100842","pmid":"30381055","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Peptidomimetics — particularly stapled peptides and macrocyclic peptides — have been successfully applied to target numerous 'undruggable' protein-protein interactions, combining the targeting capability of peptides with improved pharmacokinetic properties through conformational constraint.","whyItMatters":"Most disease-relevant protein-protein interactions cannot be targeted by conventional small-molecule drugs, creating a vast untapped therapeutic space that peptidomimetics can uniquely address.","specificNumbers":"","methodology":"Narrative review of chemical approaches for creating conformationally constrained peptidomimetics, focusing on stapled peptides and macrocyclization strategies, with examples of successful biological applications.","limitations":"As a 2018 review, it may not cover the most recent advances in peptidomimetic chemistry and clinical development. The review focuses on chemical approaches without detailed discussion of manufacturing, cost, or clinical translation challenges."},{"rthcId":"RPEP-04010","title":"Novel hGHRH homodimer promotes fertility of female infertile hamster by up-regulating ovarian GHRH receptor without triggering GH secretion.","authors":"Zhang, Juan-Hui; Zhang, Xu-Dong; Yue, Lin-Na; Guo, Xiao-Yuan; Tang, Jing-Xuan; Guo, Li-Rong; Li, Yun; Tang, Song-Shan","year":2018,"journal":"European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 117, 341-350","doi":"10.1016/j.ejps.2018.03.012","pmid":"29526766","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04011","title":"The research of the possible mechanism and the treatment for capsaicin-induced cough.","authors":"Zhang, Li; Sun, Tieying; Liu, Longteng; Wang, Lifang","year":2018,"journal":"Pulmonary pharmacology & therapeutics, 49, 1-9","doi":"10.1016/j.pupt.2017.12.008","pmid":"29288742","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In capsaicin-induced cough guinea pig model (N=10 per group, 4 groups):\n\n- Both inhaled and oral SB705498 significantly reduced cough numbers (p<0.001) and prolonged cough incubation periods (p<0.001) compared to saline control\n- Codeine (positive control) also significantly reduced coughing\n- SB705498 reduced expression of three neuropeptides in lung and brain tissue (all p<0.05): substance P (SP), calcitonin gene-related peptide (CGRP), and neurokinin A (NKA)\n- No lung or brain parenchymal inflammation was observed in any group (safety signal)\n- Both routes of SB705498 administration (inhaled and oral) were effective","whyItMatters":"Chronic cough is one of the most common reasons for doctor visits, affecting up to 10% of adults in some populations. Current antitussives are often ineffective or have significant side effects (like sedation from codeine). TRPV1 antagonists represent a mechanistically targeted approach that addresses the root cause — nerve hypersensitivity — rather than just suppressing the cough reflex centrally. The finding that neuropeptide levels decrease in both lungs and brain suggests the drug modulates the cough pathway at multiple levels.","specificNumbers":"","methodology":"Guinea pigs with capsaicin-inducible cough were randomized into four groups (N=10 each): saline inhalation (negative control), codeine injection (positive control), SB705498 inhalation, and SB705498 oral administration. After treatment, capsaicin cough challenge was repeated and cough numbers and incubation periods were recorded. ELISA and immunohistochemistry measured substance P, CGRP, and neurokinin A expression in lung and brain tissues. H&E staining assessed tissue pathology.","limitations":"Guinea pigs are the standard model for cough research but may not perfectly predict human cough responses. The capsaicin-induced cough model represents acute cough hypersensitivity rather than the complex pathology of chronic unexplained cough in humans. The study did not assess long-term safety or efficacy. SB705498 has known tolerability issues in human trials (TRPV1 antagonists can cause hyperthermia), which were not evaluated in this short-term study. The brain tissue neuropeptide changes are interesting but the functional significance for centrally mediated cough suppression needs further investigation."},{"rthcId":"RPEP-04012","title":"Efficient co-delivery of neo-epitopes using dispersion-stable layered double hydroxide nanoparticles for enhanced melanoma immunotherapy.","authors":"Zhang, Ling-Xiao; Xie, Xi-Xiu; Liu, Dong-Qun; Xu, Zhi Ping; Liu, Rui-Tian","year":2018,"journal":"Biomaterials, 174, 54-66","doi":"10.1016/j.biomaterials.2018.05.015","pmid":"29778982","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Dispersion-stable LDH nanoparticles were significantly more effective than aggregated ones, demonstrating that colloidal stability is a critical factor for vaccine efficacy. The well-dispersed formulation induced stronger cytotoxic T-lymphocyte (CTL) responses and significantly better tumor growth inhibition.\n\nA multi-target vaccine co-loading three peptide epitopes (Trp2, M27, and M30 mutated epitopes) with CpG adjuvant onto dispersion-stable LDH nanoparticles showed remarkable melanoma growth inhibition — superior to single-antigen approaches. This demonstrates that LDH nanoparticles can serve as an effective multi-antigen delivery platform for personalized cancer immunotherapy.","whyItMatters":"Personalized cancer vaccines need to deliver multiple patient-specific peptide antigens effectively to generate broad immune responses. This study identifies a practical nanoparticle platform that can carry multiple peptides simultaneously and demonstrates that a seemingly simple physical property — particle dispersion stability — makes a major difference in effectiveness. This insight could accelerate the development of multi-target personalized cancer vaccines.","specificNumbers":"","methodology":"LDH nanoparticles were prepared with controlled dispersion stability and loaded with peptide epitopes and CpG immunostimulant. Melanoma-bearing C57BL/6 mice were vaccinated with either aggregated or dispersion-stable formulations, with single or multiple peptide antigens. Anti-tumor efficacy was assessed through tumor growth measurements, and immune responses were characterized by measuring cytotoxic T-lymphocyte activity.","limitations":"This is a preclinical study in a single mouse melanoma model. The B16 melanoma model is widely used but may not represent the diversity of human cancers. The mutated epitopes were pre-selected rather than identified from individual tumors, which simplifies the personalization challenge. Long-term immune memory and potential autoimmune effects were not assessed. Translation to human use would require optimization of LDH nanoparticle formulation for clinical manufacturing."},{"rthcId":"RPEP-04013","title":"Cell-Penetrating Peptide Mediates Intracellular Membrane Passage of Human Papillomavirus L2 Protein to Trigger Retrograde Trafficking.","authors":"Zhang, Pengwei; Monteiro da Silva, Gabriel; Deatherage, Catherine; Burd, Christopher; DiMaio, Daniel","year":2018,"journal":"Cell, 174(6), 1465-1476.e13","doi":"10.1016/j.cell.2018.07.031","pmid":"30122350","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04014","title":"Proinflammatory switch from Gαs to Gαi signaling by Glucagon-like peptide-1 receptor in murine splenic monocyte following burn injury.","authors":"Zhang, Qing-Hong; Hao, Ji-Wei; Li, Guang-Lei; Ji, Xiao-Jing; Yao, Xu-Dong; Dong, Ning; Yao, Yong-Ming","year":2018,"journal":"Inflammation research : official journal of the European Histamine Research Society ... [et al.], 67(2), 157-168","doi":"10.1007/s00011-017-1104-9","pmid":"29022064","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Exendin-4 reduced TNF-α secretion from sham (healthy) monocytes but unexpectedly increased it from burn monocytes. This reversal was caused by a switch in GLP-1 receptor signaling: burn monocytes showed reduced Gαs expression and increased Gαi expression compared to sham cells. Blocking Gαi signaling with pertussis toxin reversed the pro-inflammatory effect. In burn monocytes, Exendin-4 failed to stimulate cAMP production (the normal anti-inflammatory pathway) and instead activated ERK1/2 and NF-κB pro-inflammatory pathways.","whyItMatters":"GLP-1-based therapies are increasingly used in critical care to manage hyperglycemia. This study reveals a potentially dangerous paradox: in burn-injured patients, these drugs might worsen inflammation rather than help. Understanding this signaling switch is essential for safe use of GLP-1 receptor agonists in critically ill and trauma patients, a population where blood sugar management is crucial.","specificNumbers":"","methodology":"Splenic monocytes were isolated from sham and burn-injured BALB/c mice 24 hours after injury. Cells were treated with Exendin-4 alone or with Gαi inhibitor (pertussis toxin) or PKA blocker (H89). Researchers measured cell viability (CCK-8), cytokine levels (ELISA), cAMP levels, PKA activity, NF-κB activation, ERK1/2 phosphorylation (Western blot), and GLP-1R downstream protein expression (immunofluorescence and Western blot).","limitations":"This is a mouse study using ex vivo monocyte cultures, so the findings may not directly apply to human patients. The burn model represents a specific type of injury, and the G protein switch may not occur in all inflammatory conditions. Only splenic monocytes were studied — other immune cell types may respond differently. The study used Exendin-4 specifically; other GLP-1 receptor agonists may behave differently."},{"rthcId":"RPEP-04015","title":"Identification and application of self-binding zipper-like sequences in SARS-CoV spike protein.","authors":"Zhang, Si Min; Liao, Ying; Neo, Tuan Ling; Lu, Yanning; Liu, Ding Xiang; Vahlne, Anders; Tam, James P","year":2018,"journal":"The international journal of biochemistry & cell biology, 101, 103-112","doi":"10.1016/j.biocel.2018.05.012","pmid":"29800727","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04016","title":"Prospective, randomized, blinded, and placebo-controlled study of Cerebrolysin dose-response effects on long-term functional outcomes in a rat model of mild traumatic brain injury.","authors":"Zhang, Yanlu; Chopp, Michael; Gang Zhang, Zheng; Zhang, Yi; Zhang, Li; Lu, Mei; Zhang, Talan; Winter, Stefan; Brandstätter, Hemma; Mahmood, Asim; Xiong, Ye","year":2018,"journal":"Journal of neurosurgery, 129(5), 1295-1304","doi":"10.3171/2017.6.JNS171007","pmid":"29303438","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04017","title":"Co-delivery of tumor antigen and dual toll-like receptor ligands into dendritic cell by silicon microparticle enables efficient immunotherapy against melanoma.","authors":"Zhu, Motao; Ding, Xilai; Zhao, Ruifang; Liu, Xuewu; Shen, Haifa; Cai, Chunmei; Ferrari, Mauro; Wang, Helen Y; Wang, Rong-Fu","year":2018,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 272, 72-82","doi":"10.1016/j.jconrel.2018.01.004","pmid":"29325699","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04018","title":"SS-31 Provides Neuroprotection by Reversing Mitochondrial Dysfunction after Traumatic Brain Injury.","authors":"Zhu, Yihao; Wang, Handong; Fang, Jiang; Dai, Wei; Zhou, Jiang; Wang, Xiaoliang; Zhou, Mengliang","year":2018,"journal":"Oxidative medicine and cellular longevity, 2018, 4783602","doi":"10.1155/2018/4783602","pmid":"30224944","tags":[],"studyType":"animal","evidenceStrength":"low","keyFinding":"The mitochondria-targeted peptide SS-31 (elamipretide) provided significant neuroprotection after traumatic brain injury in mice when administered 30 minutes post-injury. SS-31 reversed mitochondrial dysfunction by reducing reactive oxygen species, restoring superoxide dismutase activity, decreasing oxidative damage markers (MDA), and preventing cytochrome c release.\n\nThis translated to reduced neurological deficits, brain swelling, DNA damage, and neural cell death. Mechanistically, SS-31 restored SIRT1 expression and promoted PGC-1α nuclear translocation, suggesting it enhanced mitochondrial biogenesis — the creation of new, healthy mitochondria to replace damaged ones.","whyItMatters":"Traumatic brain injury is a leading cause of death and disability with no approved neuroprotective drugs. SS-31's ability to rapidly restore mitochondrial function after injury addresses a critical therapeutic gap. If these findings translate to humans, this peptide could be administered in emergency settings to limit the secondary brain damage that follows the initial injury.","specificNumbers":"5 mg/kg SS-31 · IP injection 30 min post-TBI · 24-hour endpoint · Reduced ROS, MDA, cytochrome c · Restored SOD, SIRT1, PGC-1α · Decreased brain edema and apoptosis","methodology":"Mouse study using a modified Marmarou weight-drop model of traumatic brain injury. Mice were randomized to sham, TBI, TBI+vehicle, or TBI+SS-31 (5 mg/kg IP, 30 min post-injury). Brain tissue was harvested at 24 hours for analysis of mitochondrial function markers, oxidative stress (ROS, SOD, MDA), cytochrome c release, SIRT1/PGC-1α expression (Western blot, immunohistochemistry), brain water content, DNA damage, and neuronal apoptosis.","limitations":"Single-dose, single-timepoint mouse study with assessment at only 24 hours post-injury. Long-term neurological outcomes and dose-response relationships were not evaluated. The weight-drop TBI model has limitations in replicating the heterogeneity of human brain injuries. Translation from mouse to human TBI has historically been challenging."},{"rthcId":"RPEP-04019","title":"The efficacy and safety of calcitonin gene-related peptide monoclonal antibody for episodic migraine: a meta-analysis.","authors":"Zhu, Yuhan; Liu, Yanyan; Zhao, Jing; Han, Qingqing; Liu, Lei; Shen, Xiaoxu","year":2018,"journal":"Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 39(12), 2097-2106","doi":"10.1007/s10072-018-3547-3","pmid":"30182284","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04020","title":"Design and Application of a DNA-Encoded Macrocyclic Peptide Library.","authors":"Zhu, Zhengrong; Shaginian, Alex; Grady, LaShadric C; O'Keeffe, Thomas; Shi, Xiangguo E; Davie, Christopher P; Simpson, Graham L; Messer, Jeffrey A; Evindar, Ghotas; Bream, Robert N; Thansandote, Praew P; Prentice, Naomi R; Mason, Andrew M; Pal, Sandeep","year":2018,"journal":"ACS chemical biology, 13(1), 53-59","doi":"10.1021/acschembio.7b00852","pmid":"29185700","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04021","title":"Mid-Regional Pro-Adrenomedullin (MR-proADM) as a Biomarker for Sepsis and Septic Shock: Narrative Review.","authors":"Önal, Uğur; Valenzuela-Sánchez, Francisco; Vandana, Kalwaje Eshwara; Rello, Jordi","year":2018,"journal":"Healthcare (Basel, Switzerland), 6(3)","doi":"10.3390/healthcare6030110","pmid":"30177659","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 22 studies reviewed, MR-proADM demonstrated strong utility as a biomarker for both diagnosing sepsis and predicting outcomes in septic shock patients. Its prognostic accuracy improved during patient follow-up, with area under the curve (AUC) values exceeding 0.8 for mortality prediction in several studies.\n\nThe biomarker's performance was enhanced when combined with other biomarkers or clinical severity scores, and it showed particularly strong correlation with the degree of organ failure. MR-proADM also showed potential value in specific subpopulations, including sepsis patients with burns or malignant tumors.","whyItMatters":"Sepsis kills millions worldwide each year, and early detection remains one of the biggest challenges in critical care medicine. Finding a reliable blood-based biomarker that can both diagnose sepsis early and predict who is most likely to deteriorate could save lives by enabling faster, more targeted treatment. MR-proADM — a stable fragment of the peptide adrenomedullin — appears to fill this role better than many existing biomarkers.","specificNumbers":"","methodology":"The authors conducted a narrative review by searching PubMed, Web of Science, and The Cochrane Library for studies on MR-proADM in sepsis. They included 22 studies, one opinion paper, and one review paper. No exclusion criteria for age, sex, ICU admission, or comorbidities were applied. The review examined both diagnostic and prognostic performance across general sepsis populations and specific subgroups.","limitations":"This is a narrative review, not a systematic review or meta-analysis, so it lacks rigorous quality assessment of included studies. No randomized controlled trials were available. The included studies varied in design, patient populations, and measurement methods. The authors acknowledge that larger prospective studies and RCTs are still needed to confirm these findings."},{"rthcId":"RPEP-04022","title":"Engineering recombinant Lactococcus lactis as a delivery vehicle for BPC-157 peptide with antioxidant activities.","authors":"Škrlec, Katja; Ručman, Rudolf; Jarc, Eva; Sikirić, Predrag; Švajger, Urban; Petan, Toni; Perišić Nanut, Milica; Štrukelj, Borut; Berlec, Aleš","year":2018,"journal":"Applied microbiology and biotechnology, 102(23), 10103-10117","doi":"10.1007/s00253-018-9333-6","pmid":"30191288","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04023","title":"Abdelaziz 2019 Development Of A Human","authors":"","year":2019,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04024","title":"Araujo Carvalho 2019 Frailty Telomere Meta","authors":"","year":2019,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04025","title":"Chairatana 2019 Dynamics Of Human Defensin","authors":"","year":2019,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04026","title":"Engel 2019 The Endogenous Oxytocin System","authors":"","year":2019,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04027","title":"Femminella 2019 Elad Liraglutide Alzheimers","authors":"","year":2019,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04028","title":"Fragale 2019 Ox1r Vta Alcohol Seeking","authors":"","year":2019,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04029","title":"Rees 2019 Rare Disease Trial Design","authors":"","year":2019,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04030","title":"Scammell 2019 Dora Abuse Liability Studies","authors":"","year":2019,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04031","title":"In Situ Hybridisation Study of Neuronal Neuropeptides Expression in Models of Mandibular Denervation with or without Inflammation: Injury Dependant Neuropeptide Plasticity.","authors":"Abd El-Aleem, Seham A; Morales-Aza, Begonia M","year":2019,"journal":"Journal of cytology & histology, 9(3)","doi":"10.4172/2157-7099.1000509","pmid":"31192032","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04032","title":"The synthetic peptide LyeTxI-b derived from Lycosa erythrognatha spider venom is cytotoxic to U-87 MG glioblastoma cells.","authors":"Abdel-Salam, Mostafa A L; Carvalho-Tavares, Juliana; Gomes, Kamila Sousa; Teixeira-Carvalho, Andrea; Kitten, Gregory T; Nyffeler, Johanna; Dias, Felipe F; Dos Reis, Pablo V Mendes; Pimenta, Adriano M C; Leist, Marcel; de Lima, Maria Elena; de Souza-Fagundes, Elaine Maria","year":2019,"journal":"Amino acids, 51(3), 433-449","doi":"10.1007/s00726-018-2678-4","pmid":"30449002","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"LyeTxI-b, a cationic alpha-helical antimicrobial peptide, showed potent cytotoxicity against U87-MG glioblastoma cells through a membranolytic mechanism. Membrane disruption occurred within 15 minutes, confirmed by trypan blue uptake, reduced calcein-AM conversion, and LDH release. Scanning electron microscopy revealed physical holes and pores in the cancer cell membranes.\n\nImaging flow cytometry confirmed that 59% of cells underwent necroptosis after 3 hours of treatment. Necrostatin-1 (a necroptosis inhibitor) partially protected cells in a dose-dependent manner, confirming the necroptosis pathway. Transmission electron microscopy showed swollen nuclei, vacuolized organelles, and electron-lucent cytoplasm. Importantly, the peptide showed only mild cytotoxicity against normal human and monkey fibroblasts and low hemolytic activity.","whyItMatters":"Glioblastoma is nearly always fatal, and current treatments (surgery, radiation, temozolomide) extend survival by only months. The ability of LyeTxI-b to rapidly kill cancer cells through membrane disruption — a physical mechanism that bacteria and cancer cells can't easily develop resistance to — makes it an intriguing candidate. The selectivity for cancer cells over normal cells addresses one of the biggest challenges in anticancer peptide development.","specificNumbers":"","methodology":"The synthetic peptide LyeTxI-b was tested on U87-MG glioblastoma cells and normal fibroblast lines. Cell viability was assessed by multiple assays (trypan blue, calcein-AM, LDH release). Cell morphology was examined by scanning and transmission electron microscopy. Cell death pathways were characterized using imaging flow cytometry and the necroptosis inhibitor necrostatin-1. Hemolytic activity was tested on human red blood cells.","limitations":"This was entirely an in vitro study on a single glioblastoma cell line (U87-MG). No animal tumor models were tested. The selectivity between cancer and normal cells, while encouraging, was observed in cell culture conditions that don't replicate the blood-brain barrier challenge of reaching brain tumors. Stability, pharmacokinetics, and immunogenicity of the peptide in vivo are unknown. The mechanism of cancer cell selectivity (likely related to membrane charge differences) was not fully elucidated."},{"rthcId":"RPEP-04033","title":"Neutrophil α-defensins promote thrombosis in vivo by altering fibrin formation, structure, and stability.","authors":"Abu-Fanne, Rami; Stepanova, Victoria; Litvinov, Rustem I; Abdeen, Suhair; Bdeir, Khalil; Higazi, Mohamed; Maraga, Emad; Nagaswami, Chandrasekaran; Mukhitov, Alexander R; Weisel, John W; Cines, Douglas B; Higazi, Abd Al-Roof","year":2019,"journal":"Blood, 133(5), 481-493","doi":"10.1182/blood-2018-07-861237","pmid":"30442678","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04034","title":"Discovery of Peptide Antibiotics Composed of d-Amino Acids.","authors":"Adaligil, Emel; Patil, Kalyani; Rodenstein, Marissa; Kumar, Krishna","year":2019,"journal":"ACS chemical biology, 14(7), 1498-1506","doi":"10.1021/acschembio.9b00234","pmid":"31243959","tags":["antimicrobial-peptides","peptide-design"],"studyType":"basic-research","evidenceStrength":"preliminary","keyFinding":"Researchers used a 'mirror image phage display' technique to discover short peptide antibiotics made entirely of D-amino acids (the mirror image of natural L-amino acids). These peptides — in linear, cyclic, and bicyclic forms — killed Staphylococcus aureus, MRSA, and vancomycin-resistant Enterococci (VRE) with moderately high antibacterial activity. Crucially, they showed no toxicity to human red blood cells or mammalian cells at active concentrations.\n\nBecause D-amino acid peptides are not recognized by the body's protein-degrading enzymes, they are metabolically stable and could potentially be delivered orally — a major advantage over natural peptide antibiotics that are quickly destroyed in the gut.","whyItMatters":"Vancomycin is often the 'antibiotic of last resort' for serious infections. The emergence of vancomycin-resistant bacteria is one of the most dangerous developments in antibiotic resistance. These D-amino acid peptides represent a fundamentally new class of antibiotics that bacteria have never encountered before, making resistance development less likely. Their stability and potential for oral delivery could make them practical clinical drugs rather than just lab curiosities.","specificNumbers":"D-amino acid peptides · Active against S. aureus, MRSA, VRE · Linear, cyclic, and bicyclic forms · No toxicity to human RBCs or mammalian cells · Mirror image phage display platform","methodology":"Mirror image phage display — researchers designed enantiomeric (mirror image) versions of bacterial cell wall precursors as targets, then screened peptide libraries against them. The selected peptides, composed of D-amino acids, were synthesized and tested for antibacterial activity against S. aureus, MRSA, and VRE. Toxicity was assessed against human red blood cells and HeLa mammalian cells.","limitations":"All testing was in vitro (lab dish) — no animal models were used. 'Moderately high' antibacterial activity suggests the peptides need further optimization before they could match the potency of existing antibiotics. The manufacturing cost and scalability of D-amino acid peptides for clinical use is not addressed. In vivo pharmacokinetics, biodistribution, and efficacy remain unknown."},{"rthcId":"RPEP-04035","title":"The Growth Hormone Releasing Hormone Analogue, Tesamorelin, Decreases Muscle Fat and Increases Muscle Area in Adults with HIV.","authors":"Adrian, S; Scherzinger, A; Sanyal, A; Lake, J E; Falutz, J; Dubé, M P; Stanley, T; Grinspoon, S; Mamputu, J-C; Marsolais, C; Brown, T T; Erlandson, K M","year":2019,"journal":"The Journal of frailty & aging, 8(3), 154-159","doi":"10.14283/jfa.2018.45","pmid":"31237318","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04036","title":"Role of Molybdenum-Containing Enzymes in the Biotransformation of the Novel Ghrelin Receptor Inverse Agonist PF-5190457: A Reverse Translational Bed-to-Bench Approach.","authors":"Adusumalli, Sravani; Jamwal, Rohitash; Obach, R Scott; Ryder, Tim F; Leggio, Lorenzo; Akhlaghi, Fatemeh","year":2019,"journal":"Drug metabolism and disposition: the biological fate of chemicals, 47(8), 874-882","doi":"10.1124/dmd.119.087015","pmid":"31182423","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04037","title":"Coupling the Antimalarial Cell Penetrating Peptide TP10 to Classical Antimalarial Drugs Primaquine and Chloroquine Produces Strongly Hemolytic Conjugates.","authors":"Aguiar, Luísa; Biosca, Arnau; Lantero, Elena; Gut, Jiri; Vale, Nuno; Rosenthal, Philip J; Nogueira, Fátima; Andreu, David; Fernàndez-Busquets, Xavier; Gomes, Paula","year":2019,"journal":"Molecules (Basel, Switzerland), 24(24)","doi":"10.3390/molecules24244559","pmid":"31842498","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Chloroquine-TP10 conjugates showed higher antiplasmodial activity than the parent TP10 peptide alone. However, both chloroquine-TP10 and primaquine-TP10 conjugates exhibited strong hemolytic activity — they bound to and destroyed red blood cell membranes, as demonstrated by fluorescence microscopy and flow cytometry.\n\nThis is a critical negative finding: despite cell-penetrating peptides being widely reported as safe and effective carriers for diverse cargoes (from small drugs to large biomolecules), coupling them to aminoquinoline antimalarials specifically produces unacceptable hemolysis. The authors conclude that cell-penetrating peptides are unsuitable for safe intracellular delivery of this drug class and urge researchers to systematically assess hemolytic effects in all peptide-drug conjugate development.","whyItMatters":"Malaria kills over 600,000 people annually, and drug resistance is a growing threat. Cell-penetrating peptides were seen as a promising strategy to enhance drug delivery into infected red blood cells. This study provides a critical safety warning that could prevent wasted research effort and, more importantly, prevent potential harm if such conjugates were advanced without proper hemolysis testing. It also highlights a broader principle: peptide-drug conjugates can have emergent toxicities that neither component shows alone.","specificNumbers":"","methodology":"Multiple chloroquine-TP10 and primaquine-TP10 conjugates were synthesized and tested for antiplasmodial activity against P. falciparum. Hemolytic activity was assessed using red blood cell lysis assays. Fluorescence microscopy and flow cytometry were used to visualize and quantify conjugate binding to erythrocyte membranes. A panel of different cell-penetrating peptides was tested to determine if the effect was specific to TP10.","limitations":"The study focused on aminoquinoline antimalarials (chloroquine, primaquine) specifically, so the hemolysis finding may not apply to other drug classes conjugated to CPPs. The range of cell-penetrating peptides tested was limited. In vivo antimalarial activity and hemolysis were not assessed — the findings are based on in vitro assays. The mechanism of hemolysis (whether driven by the peptide, the drug, or the conjugation chemistry) was not fully dissected."},{"rthcId":"RPEP-04038","title":"Cocaine Blocks Effects of Hunger Hormone, Ghrelin, Via Interaction with Neuronal Sigma-1 Receptors.","authors":"Aguinaga, David; Medrano, Mireia; Cordomí, Arnau; Jiménez-Rosés, Mireia; Angelats, Edgar; Casanovas, Mireia; Vega-Quiroga, Ignacio; Canela, Enric I; Petrovic, Milos; Gysling, Katia; Pardo, Leonardo; Franco, Rafael; Navarro, Gemma","year":2019,"journal":"Molecular neurobiology, 56(2), 1196-1210","doi":"10.1007/s12035-018-1140-7","pmid":"29876881","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04039","title":"Neurodegenerative Disease-Related Proteins within the Epidermal Layer of the Human Skin.","authors":"Akerman, S Can; Hossain, Shireen; Shobo, Adeola; Zhong, Yifei; Jourdain, Roland; Hancock, Mark A; George, Kelly; Breton, Lionel; Multhaup, Gerhard","year":2019,"journal":"Journal of Alzheimer's disease : JAD, 69(2), 463-478","doi":"10.3233/JAD-181191","pmid":"31006686","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04040","title":"PANCREATIC SAFETY IN STUDIES OF THE GLUCAGON-LIKE PEPTIDE-1 RECEPTOR AGONIST ALBIGLUTIDE.","authors":"Al-Kawas, Firas; Anderson, Michelle Ann; Enns, Robert; Wilson, Timothy H; Johnson, Susan; Mallory, Jason M","year":2019,"journal":"Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists, 25(7), 698-716","doi":"10.4158/EP-2018-0507","pmid":"30865522","tags":["glp-1"],"studyType":"post-hoc-analysis","evidenceStrength":"strong","keyFinding":"An independent expert panel reviewed all suspected pancreatitis cases across the entire HARMONY Phase III clinical program for albiglutide (a GLP-1 receptor agonist). Of 4,895 patients studied, 43 had potential pancreatitis cases, of which 11 were adjudicated as definite or probable acute pancreatitis (8 on albiglutide, 3 on active comparators). The pancreatitis rate with albiglutide was 0.3% (6/2,365) compared to 0% with placebo (0/486) and 0.08% with non-GLP-1RA active comparators (2/2,062 — but both confirmed cases in the comparator group were actually in patients receiving a different GLP-1RA).\n\nWhile pancreatitis was uncommon overall, the rate was numerically higher with albiglutide than placebo, and the independent committee judged most cases as at least possibly related to the drug.","whyItMatters":"Whether GLP-1 drugs cause pancreatitis has been one of the most debated safety questions in diabetes medicine for over a decade. This rigorous independent review of nearly 5,000 patients provides some of the most carefully adjudicated data on the topic. While absolute rates were low, the signal is there — and it matters because millions of people now take GLP-1 drugs for diabetes and weight loss.","specificNumbers":"n=4,895 · 2,365 on albiglutide · 43 suspected cases reviewed · 11 adjudicated definite/probable · Albiglutide: 0.3% · Placebo: 0% · Active comparators: 0.08% · 6/8 albiglutide cases possibly drug-related","methodology":"Independent pancreatitis adjudication committee (PAC) of gastroenterology and pancreatic disease experts prospectively reviewed all suspected acute pancreatitis cases from 8 HARMONY Phase III clinical trials. Cases were classified as definite, probable, possible, or unlikely pancreatitis, and relationship to study drug was assessed. Data came from 2,365 albiglutide patients and 2,530 comparator patients.","limitations":"The number of pancreatitis events was small (11 adjudicated cases), limiting statistical power for definitive conclusions. The placebo group (486 patients) was relatively small compared to active treatment groups. Albiglutide has since been withdrawn from the market (for commercial, not safety, reasons), so these data are most relevant as part of the broader GLP-1 class safety picture. The study could not determine whether pancreatitis risk is dose- or duration-dependent."},{"rthcId":"RPEP-04041","title":"Amygdala-Hippocampal Connectivity Is Associated With Endogenous Levels of Oxytocin and Can Be Altered by Exogenously Administered Oxytocin in Adults With Autism.","authors":"Alaerts, Kaat; Bernaerts, Sylvie; Vanaudenaerde, Bart; Daniels, Nicky; Wenderoth, Nicole","year":2019,"journal":"Biological psychiatry. Cognitive neuroscience and neuroimaging, 4(7), 655-663","doi":"10.1016/j.bpsc.2019.01.008","pmid":"30846366","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04042","title":"Cracking the combination: Gut hormones for the treatment of obesity and diabetes.","authors":"Alexiadou, Kleopatra; Anyiam, Oluwaseun; Tan, Tricia","year":2019,"journal":"Journal of neuroendocrinology, 31(5), e12664","doi":"10.1111/jne.12664","pmid":"30466162","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04043","title":"Use of Mass Spectrometry to Profile Peptides in Whey Protein Isolate Medium Fermented by Lactobacillus helveticus LH-2 and Lactobacillus acidophilus La-5.","authors":"Ali, Eman; Nielsen, Søren D; Abd-El Aal, Salah; El-Leboudy, Ahlam; Saleh, Ebeed; LaPointe, Gisèle","year":2019,"journal":"Frontiers in nutrition, 6, 152","doi":"10.3389/fnut.2019.00152","pmid":"31681785","tags":["bioactive-peptides","food-science"],"studyType":"laboratory-study","evidenceStrength":"moderate","keyFinding":"Two probiotic bacteria (L. helveticus LH-2 and L. acidophilus La-5) fermenting whey protein produced unique peptide profiles. Unfermented whey contained 109 milk-derived peptides, 39 of which had known bioactivities (ACE inhibitory, antioxidant, antimicrobial, immunomodulating). Fermentation dramatically reshaped this profile — LH-2 produced 75 peptides and La-5 produced 15.\n\nThe fermented peptide mixtures downregulated virulence genes (hilA and ssrB) in Salmonella Typhimurium, reducing its ability to cause disease. Crucially, when Salmonella's peptide transporter (oppA) was knocked out, this anti-virulence effect disappeared — suggesting Salmonella must actively import these peptides for them to suppress virulence.\n\nThis means probiotic fermentation of whey creates bioactive peptides that can directly disarm a dangerous pathogen by getting inside it.","whyItMatters":"This study connects three areas: food science, probiotics, and antimicrobial peptides. It shows that the health benefits of fermented dairy may come partly from specific peptides created during fermentation that can disarm pathogens like Salmonella — not just by competing for space in the gut, but by actively suppressing bacterial virulence genes. This could lead to new anti-infective strategies based on food-derived peptides.","specificNumbers":"109 peptides in unfermented whey · 39 with known bioactivities · 75 peptides in LH-2 ferment · 15 in La-5 ferment · hilA and ssrB virulence genes downregulated · oppA mutant = no effect","methodology":"Whey protein isolate medium (5.6% WPI) was fermented by two Lactobacillus strains. The <3 kDa peptide fraction was analyzed by mass spectrometry and compared to unfermented controls. Peptide sequences were searched against databases for known bioactivities. The peptide-containing spent media were tested against Salmonella Typhimurium DT104 for virulence gene expression (hilA, ssrB) by qPCR. An oppA peptide transporter mutant was used to test whether Salmonella's uptake of peptides was required for the effect.","limitations":"In vitro study — the anti-virulence effects were observed in laboratory conditions, not in the gut of living organisms. The specific peptides responsible for virulence gene downregulation were not individually identified. The 3 kDa filtrate may contain non-peptide molecules that contribute to the observed effects. Relevance to human Salmonella infection is not established."},{"rthcId":"RPEP-04044","title":"Cytosolic Delivery of Macromolecules in Live Human Cells Using the Combined Endosomal Escape Activities of a Small Molecule and Cell Penetrating Peptides.","authors":"Allen, Jason; Najjar, Kristina; Erazo-Oliveras, Alfredo; Kondow-McConaghy, Helena M; Brock, Dakota J; Graham, Kristin; Hager, Elizabeth C; Marschall, Andrea L J; Dübel, Stefan; Juliano, Rudolph L; Pellois, Jean-Philippe","year":2019,"journal":"ACS chemical biology, 14(12), 2641-2651","doi":"10.1021/acschembio.9b00585","pmid":"31633910","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04045","title":"Effect of gluten diet on blood innate immune gene expressions and stool consistency in Spix's Saddleback Tamarin (Leontocebus fuscicollis) raised in captivity.","authors":"Almeida, Taianara Tocantins Gomes; Monteiro, Maria Vivina Barros; Guimarães, Rafaelle Casseb; Casseb, Alexandre Rosário; Huffman, Michael Alan; Gonçalves, Evonnildo Costa; Monteiro, Frederico Ozanan Barros; Silva Filho, Ednaldo","year":2019,"journal":"Molecular biology reports, 46(4), 3617-3623","doi":"10.1007/s11033-018-04576-8","pmid":"31201676","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04046","title":"Responder Analyses from a Phase 2b Dose-Ranging Study of Bremelanotide.","authors":"Althof, Stanley; Derogatis, Leonard R; Greenberg, Sally; Clayton, Anita H; Jordan, Robert; Lucas, Johna; Spana, Carl","year":2019,"journal":"The journal of sexual medicine, 16(8), 1226-1235","doi":"10.1016/j.jsxm.2019.05.012","pmid":"31277966","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"For the bremelanotide 1.75 mg dose in the overall modified intention-to-treat population:\n\n- All 7 endpoints achieved statistical significance vs. placebo (p ≤ 0.03)\n- Endpoints included: FSFI-desire domain, FSDS-DAO total score, FSDS-DAO items 13 and 14, and number of satisfying sexual events\n- Minimal clinically important differences (MCIDs) determined by ROC curves matched expert clinical estimates\n- The drug was safe and well tolerated\n- These responder definitions were used in the subsequent Phase 3 RECONNECT registration trials\n\nMultiple responder analysis methods (historical anchors, self-reported global benefit, ROC curves, cumulative distribution) converged on the same conclusions, strengthening confidence in the clinical meaningfulness of the improvements.","whyItMatters":"Hypoactive sexual desire disorder affects an estimated 10% of premenopausal women and had very limited treatment options before bremelanotide. This study is important not just for its clinical findings but for its methodological contribution — establishing how to measure clinically meaningful change in sexual function, a subjective and complex outcome. The 1.75 mg dose identified here became the approved dose for Vyleesi (bremelanotide), the first FDA-approved on-demand treatment for low sexual desire in women.","specificNumbers":"","methodology":"Responder analyses were performed on data from a large, controlled, Phase 2b dose-finding study of bremelanotide in premenopausal women with HSDD and mixed HSDD/FSAD. Seven patient-reported outcome endpoints were assessed using four types of responder analyses: planned analyses anchored to expert-estimated MCIDs, post hoc analyses based on self-reported global benefit, ROC curve analyses, and cumulative distribution functions. Analyses were performed for all FSD diagnoses combined, HSDD alone, and FSAD/mixed groups.","limitations":"The MCIDs were derived from the same clinical trial data, ideally they should be validated in independent populations. The study enrolled only premenopausal women, so results may not apply to postmenopausal women. Sexual function endpoints are subjective and influenced by relationship factors, mood, and expectations — all difficult to control in clinical trials. The placebo response in sexual dysfunction trials is typically substantial, which was accounted for by the single-blind phase but may still affect interpretation. Specific response rates and effect sizes for each endpoint are not detailed in the abstract."},{"rthcId":"RPEP-04047","title":"Synergistic long-range effects of mutations underlie aggregation propensities of amylin analogues.","authors":"Alves, Nelson A; Dias, Luis G; Frigori, Rafael B","year":2019,"journal":"Journal of molecular modeling, 25(9), 263","doi":"10.1007/s00894-019-4137-x","pmid":"31428870","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04048","title":"Designing and enhancing the antifungal activity of corneal specific cell penetrating peptide using gelatin hydrogel delivery system.","authors":"Amit, Chatterjee; Muralikumar, Shalini; Janaki, Sargunam; Lakshmipathy, Meena; Therese, Kulandai Lily; Umashankar, Vetrivel; Padmanabhan, Prema; Narayanan, Janakiraman","year":2019,"journal":"International journal of nanomedicine, 14, 605-622","doi":"10.2147/IJN.S184911","pmid":"30697045","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04049","title":"Menadione (vitamin K3) inhibits hydrogen sulfide and substance P via NF-кB pathway in caerulein-induced acute pancreatitis and associated lung injury in mice.","authors":"Amiti; Tamizhselvi, Ramasamy; Manickam, Venkatraman","year":2019,"journal":"Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.], 19(2), 266-273","doi":"10.1016/j.pan.2019.01.012","pmid":"30685119","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04050","title":"GLP-1 receptor agonists and cardiovascular outcome trials: An update.","authors":"Andrikou, Eirini; Tsioufis, Costas; Andrikou, Ioannis; Leontsinis, Ioannis; Tousoulis, Dimitrios; Papanas, Nikolaos","year":2019,"journal":"Hellenic journal of cardiology : HJC = Hellenike kardiologike epitheorese, 60(6), 347-351","doi":"10.1016/j.hjc.2018.11.008","pmid":"30528435","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04051","title":"Designing Cell-Permeable Macrocyclic Peptides.","authors":"Appiah Kubi, George; Dougherty, Patrick G; Pei, Dehua","year":2019,"journal":"Methods in molecular biology (Clifton, N.J.), 2001, 41-59","doi":"10.1007/978-1-4939-9504-2_3","pmid":"31134566","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04052","title":"Exploring nanofibrous self-assembling peptide hydrogels using mouse myoblast cells for three-dimensional bioprinting and tissue engineering applications.","authors":"Arab, Wafaa; Kahin, Kowther; Khan, Zainab; Hauser, Charlotte A E","year":2019,"journal":"International journal of bioprinting, 5(2), 198","doi":"10.18063/ijb.v5i2.198","pmid":"32596536","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04053","title":"Anti-tumour effects of antimicrobial peptides, components of the innate immune system, against haematopoietic tumours in Drosophila mxc mutants.","authors":"Araki, Mayo; Kurihara, Massanori; Kinoshita, Suzuko; Awane, Rie; Sato, Tetsuya; Ohkawa, Yasuyuki; Inoue, Yoshihiro H","year":2019,"journal":"Disease models & mechanisms, 12(6)","doi":"10.1242/dmm.037721","pmid":"31160313","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04054","title":"Comparative efficacy, safety, and cardiovascular outcomes with once-weekly subcutaneous semaglutide in the treatment of type 2 diabetes: Insights from the SUSTAIN 1-7 trials.","authors":"Aroda, V R; Ahmann, A; Cariou, B; Chow, F; Davies, M J; Jódar, E; Mehta, R; Woo, V; Lingvay, I","year":2019,"journal":"Diabetes & metabolism, 45(5), 409-418","doi":"10.1016/j.diabet.2018.12.001","pmid":"30615985","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04055","title":"Amount of Collagen in the Meat Contained in Japanese Daily Dishes and the Collagen Peptide Content in Human Blood after Ingestion of Cooked Fish Meat.","authors":"Asai, Tomoko; Takahashi, Akira; Ito, Kumie; Uetake, Tatsuo; Matsumura, Yasuki; Ikeda, Kaori; Inagaki, Nobuya; Nakata, Masahiro; Imanishi, Yoshiharu; Sato, Kenji","year":2019,"journal":"Journal of agricultural and food chemistry, 67(10), 2831-2838","doi":"10.1021/acs.jafc.8b06896","pmid":"30784272","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Most Japanese daily dishes contain 0.2-2.5 g of collagen per meat serving, with collagen-rich foods (beef tendon, eel with skin, skinned shark tail) containing 7.6-13.3 g. After ingesting cooked shark meat, nine collagen di- and tripeptides were detected in plasma. The area under the curve for most peptides was approximately 30% of that after ingesting collagen hydrolysate with an equivalent collagen amount (except Hyp-Gly and Pro-Hyp-Gly). In vitro digestion with pepsin and pancreatin liberated only ~30% of total meat collagen into solution, explaining the lower bioavailability from whole food.","whyItMatters":"The collagen supplement market is worth billions, but consumers often wonder whether eating collagen-rich foods could provide similar benefits. This study provides direct evidence that collagen from food is significantly less bioavailable than from supplements (~30%), primarily because the collagen matrix in cooked meat is harder for digestive enzymes to access. This helps inform consumer and clinical decisions about collagen intake strategies.","specificNumbers":"","methodology":"Researchers measured collagen content in meats from typical Japanese dishes. Human volunteers consumed cooked shark meat, and blood samples were collected to measure nine specific collagen di- and tripeptides using plasma analysis (AUC determination). Results were compared to previously published data on collagen hydrolysate supplement bioavailability. In vitro digestion experiments using pepsin and pancreatin quantified how much collagen in meat could be broken down by digestive enzymes.","limitations":"The study used a small number of participants and focused on cooked shark meat, which may differ in digestibility from other collagen-rich foods. In vitro digestion may not perfectly replicate human gastrointestinal conditions. Comparison between food and supplement bioavailability used AUC data rather than standardized clinical endpoints. The study measured peptide levels in blood but did not assess whether these levels are sufficient for health benefits. Japanese dietary patterns may not generalize to other cuisines."},{"rthcId":"RPEP-04056","title":"Stressors Due to Handling Impair Gut Immunity in Meagre (Argyrosomus regius): The Compensatory Role of Dietary L-Tryptophan.","authors":"Asencio-Alcudia, Gloria; Andree, Karl B; Giraldez, Inmaculada; Tovar-Ramirez, Dariel; Alvarez-González, Alfonso; Herrera, Marcelino; Gisbert, Enric","year":2019,"journal":"Frontiers in physiology, 10, 547","doi":"10.3389/fphys.2019.00547","pmid":"31133878","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04057","title":"Hitting Undruggable Targets: Viewing Stabilized Peptide Development through the Lens of Quantitative Systems Pharmacology.","authors":"Atangcho, Lydia; Navaratna, Tejas; Thurber, Greg M","year":2019,"journal":"Trends in biochemical sciences, 44(3), 241-257","doi":"10.1016/j.tibs.2018.11.008","pmid":"30563724","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04058","title":"Utility of Neuronal-Derived Exosomes to Examine Molecular Mechanisms That Affect Motor Function in Patients With Parkinson Disease: A Secondary Analysis of the Exenatide-PD Trial.","authors":"Athauda, Dilan; Gulyani, Seema; Karnati, Hanuma Kumar; Li, Yazhou; Tweedie, David; Mustapic, Maja; Chawla, Sahil; Chowdhury, Kashfia; Skene, Simon S; Greig, Nigel H; Kapogiannis, Dimitrios; Foltynie, Thomas","year":2019,"journal":"JAMA neurology, 76(4), 420-429","doi":"10.1001/jamaneurol.2018.4304","pmid":"30640362","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 60 Parkinson's patients from the Exenatide-PD trial, neuron-derived exosomes revealed:\n- Exenatide significantly increased tyrosine phosphorylation of insulin receptor substrate 1 at 48 weeks (p=0.003) and 60 weeks (p=0.01)\n- Total Akt expression was elevated in the exenatide group (p<0.001)\n- Phosphorylated mTOR was increased (p=0.02)\n- Motor function improvements (MDS-UPDRS Part 3 scores) correlated significantly with total mTOR levels (p=0.001) and phosphorylated mTOR levels (p=0.04)\n\nThese changes persisted even 12 weeks after stopping the drug (60-week timepoint), suggesting sustained neuroprotective effects rather than just symptomatic relief.","whyItMatters":"This study is groundbreaking for two reasons: First, it provides mechanistic evidence that a GLP-1 peptide drug can engage brain insulin signaling pathways in Parkinson's patients — supporting the hypothesis that impaired brain insulin signaling contributes to PD. Second, it demonstrates a revolutionary biomarker approach: using neuron-derived exosomes from a simple blood draw to measure what drugs are doing inside brain cells, which could transform clinical trial design for neurological diseases.","specificNumbers":"","methodology":"Secondary analysis of the Exenatide-PD randomized controlled trial (60 patients, 31 exenatide, 29 placebo, 48 weeks treatment plus 12-week washout). Neuronal-derived extracellular vesicles (exosomes) were isolated from serum using anti-L1CAM antibodies, enriching for brain-origin vesicles. Proteins of interest in the insulin/Akt/mTOR signaling cascades were quantified using electrochemiluminescence assays.","limitations":"This was a secondary analysis of a relatively small trial (60 patients), not designed primarily to test these mechanistic endpoints. The exosome isolation technique, while innovative, captures a mixed population of extracellular vesicles that may not perfectly represent neuronal biology. The correlation between mTOR levels and motor improvement doesn't prove causation. One patient's data was excluded from the exenatide group, and the reasons are not detailed in the abstract."},{"rthcId":"RPEP-04059","title":"Retinoprotective Effects of TAT-Bound Vasoactive Intestinal Peptide and Pituitary Adenylate Cyclase Activating Polypeptide.","authors":"Atlasz, Tamas; Werling, D; Song, S; Szabo, E; Vaczy, A; Kovari, P; Tamas, A; Reglodi, D; Yu, Rongjie","year":2019,"journal":"Journal of molecular neuroscience : MN, 68(3), 397-407","doi":"10.1007/s12031-018-1229-5","pmid":"30542799","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04060","title":"Locally delivered GLP-1 analogues liraglutide and exenatide enhance microvascular perfusion in individuals with and without type 2 diabetes.","authors":"Aung, Myo Myo; Slade, Kate; Freeman, Leighton A R; Kos, Katarina; Whatmore, Jacqueline L; Shore, Angela C; Gooding, Kim M","year":2019,"journal":"Diabetologia, 62(9), 1701-1711","doi":"10.1007/s00125-019-4918-x","pmid":"31203378","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04061","title":"Pharmacokinetics and efficacy of PT302, a sustained-release Exenatide formulation, in a murine model of mild traumatic brain injury.","authors":"Bader, Miaad; Li, Yazhou; Lecca, Daniela; Rubovitch, Vardit; Tweedie, David; Glotfelty, Elliot; Rachmany, Lital; Kim, Hee Kyung; Choi, Ho-Il; Hoffer, Barry J; Pick, Chaim G; Greig, Nigel H; Kim, Dong Seok","year":2019,"journal":"Neurobiology of disease, 124, 439-453","doi":"10.1016/j.nbd.2018.11.023","pmid":"30471415","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04062","title":"Clinical Outcomes in Patients With Type 2 Diabetes Mellitus and Peripheral Artery Disease: Results From the EXSCEL Trial.","authors":"Badjatiya, Anish; Merrill, Peter; Buse, John B; Goodman, Shaun G; Katona, Brian; Iqbal, Nayyar; Pagidipati, Neha J; Sattar, Naveed; Holman, Rury R; Hernandez, Adrian F; Mentz, Robert J; Patel, Manesh R; Jones, W Schuyler","year":2019,"journal":"Circulation. Cardiovascular interventions, 12(12), e008018","doi":"10.1161/CIRCINTERVENTIONS.119.008018","pmid":"31752517","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 14,752 EXSCEL participants, 2,800 (19%) had PAD at baseline. PAD patients versus non-PAD patients had:\n\n- Higher MACE rates: 13.6% vs 11.4% (adjusted HR 1.13, 95% CI 1.00-1.27, P=0.047)\n- Higher all-cause mortality: adjusted HR 1.38 (95% CI 1.20-1.60, P<0.001)\n- Higher LEA rates\n\nExenatide versus placebo showed no differences in MACE or lower-extremity amputation rates, regardless of PAD status. This means exenatide was neither beneficial nor harmful in this high-risk population.","whyItMatters":"Patients with both diabetes and PAD face extremely high cardiovascular risk and are at particular risk for lower-extremity amputation — a concern heightened after a diabetes drug (canagliflozin) was linked to increased amputation risk. This analysis provides safety reassurance that exenatide does not increase amputation risk in PAD patients. However, it also shows that exenatide does not provide the cardiovascular protection that newer GLP-1 agonists like semaglutide and liraglutide have demonstrated.","specificNumbers":"","methodology":"Post hoc analysis of the EXSCEL trial, a double-blind, placebo-controlled randomized trial evaluating once-weekly exenatide versus placebo in patients with type 2 diabetes. The primary endpoint was composite MACE (cardiovascular death, myocardial infarction, or stroke). This subgroup analysis assessed outcomes in patients with and without baseline PAD, with adjusted hazard ratios accounting for baseline characteristics.","limitations":"This is a post hoc subgroup analysis, not a prespecified primary analysis, so it may be underpowered for detecting smaller treatment effects. PAD was defined by baseline medical history, which may undercount undiagnosed cases. Once-weekly exenatide is an older formulation; results may not apply to newer, more potent GLP-1 RAs. The null result for exenatide in PAD patients cannot be extrapolated to other GLP-1 drugs that have shown cardiovascular benefit."},{"rthcId":"RPEP-04063","title":"Emerging targets for cough therapies; NK1 receptor antagonists.","authors":"Badri, Huda; Smith, Jaclyn A","year":2019,"journal":"Pulmonary pharmacology & therapeutics, 59, 101853","doi":"10.1016/j.pupt.2019.101853","pmid":"31622673","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04064","title":"Cardiovascular protection in type 2 diabetes: Insights from recent outcome trials.","authors":"Bailey, Clifford J; Marx, Nikolaus","year":2019,"journal":"Diabetes, obesity & metabolism, 21(1), 3-14","doi":"10.1111/dom.13492","pmid":"30091169","tags":[],"studyType":"review","evidenceStrength":"high","keyFinding":"This review of major cardiovascular outcome trials found that GLP-1 receptor agonists (liraglutide in the LEADER trial, semaglutide in the SUSTAIN-6 trial) significantly reduced major adverse cardiac events (MACE) in people with type 2 diabetes. SGLT2 inhibitors (empagliflozin in EMPA-REG OUTCOME, canagliflozin in CANVAS) also significantly reduced MACE and hospitalizations for heart failure. DPP-4 inhibitors showed cardiovascular neutrality — they neither increased nor decreased MACE — though a small increased risk of heart failure with some members of the class could not be ruled out.\n\nImportantly, the review notes that most trial participants had already experienced cardiovascular events, meaning these results primarily reflect secondary prevention. The majority of people with type 2 diabetes who take these medications have not had prior cardiovascular events, so how these benefits translate to primary prevention remains an open question.","whyItMatters":"Heart disease is the leading cause of death among people with type 2 diabetes. For years, diabetes drugs were evaluated primarily on their ability to lower blood sugar, with cardiovascular effects largely unknown. This generation of outcome trials — mandated by regulators after safety concerns with earlier drugs — shifted the landscape by showing that some newer glucose-lowering therapies actively protect the heart, not just avoid harming it. These findings have reshaped diabetes treatment guidelines worldwide.","specificNumbers":"","methodology":"The authors reviewed data from multiple large, randomized controlled cardiovascular outcome trials, including LEADER (liraglutide), SUSTAIN-6 (semaglutide), EMPA-REG OUTCOME (empagliflozin), and CANVAS (canagliflozin), as well as trials of DPP-4 inhibitors. They examined composite MACE outcomes (cardiovascular death, non-fatal heart attack, and non-fatal stroke) and heart failure hospitalization across these trials.","limitations":"As a narrative review, this study did not perform independent meta-analysis. Direct comparisons between trials are limited by differences in patient populations, cardiovascular risk at enrollment, trial designs, and analytical methods. Most trial participants had pre-existing cardiovascular disease, so results may not apply to lower-risk patients who make up the majority of the type 2 diabetes population."},{"rthcId":"RPEP-04065","title":"Vasoactive Intestinal Peptide Deficiency Is Associated With Altered Gut Microbiota Communities in Male and Female C57BL/6 Mice.","authors":"Bains, Manpreet; Laney, Caleb; Wolfe, Annie E; Orr, Megan; Waschek, James A; Ericsson, Aaron C; Dorsam, Glenn P","year":2019,"journal":"Frontiers in microbiology, 10, 2689","doi":"10.3389/fmicb.2019.02689","pmid":"31849864","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"VIP knockout mice (VIP-/-) showed significant changes in gut bacterial composition, reduced biodiversity, and weight loss compared to wild-type (VIP+/+) and heterozygous (VIP+/-) littermates, regardless of sex. The altered microbiome profile in VIP-deficient mice resembled microbial changes reported in inflammatory and autoimmune disorders. Predictive functional analysis using PICRUSt software suggested an energy surplus within the altered microbiota, indicating shifts in bacterial metabolic function. These effects were consistent across 47 mice of both sexes.","whyItMatters":"The gut microbiome profoundly influences health, from immune function to metabolism and mental health. Showing that a single neuropeptide — VIP — is essential for maintaining normal gut bacterial communities establishes a direct link between the nervous system's peptide signaling and microbiome homeostasis. This could have implications for understanding conditions where VIP signaling is disrupted, including inflammatory bowel disease, autoimmune disorders, and neurodegenerative diseases.","specificNumbers":"","methodology":"Researchers collected fecal samples from 47 mice across three genotypes (VIP+/+, VIP+/-, and VIP-/-) of both sexes, all from the same litters to control for environmental and maternal effects. They performed 16S rRNA gene sequencing to characterize gut bacterial communities and used PICRUSt software to predict functional changes in the microbiome. Body weight was also tracked.","limitations":"This study used a genetic knockout model where VIP is absent from birth, which may trigger developmental compensatory changes not relevant to adult VIP dysfunction. The 16S rRNA sequencing identifies bacterial taxa but doesn't directly measure their functional effects. PICRUSt predictions are computational estimates, not direct measurements of microbial metabolism. The mouse gut microbiome differs from the human microbiome, so the specific bacterial changes may not translate directly."},{"rthcId":"RPEP-04066","title":"Targeted transcript analysis revealed association of suboptimal expression of certain endometrial immunity-related genes with disparate uterine diseases in zebu cows.","authors":"Baithalu, R K; Singh, S K; Kumaresan, A; Kumar, S; Maharana, B R; Mallick, S; Mohanty, T K; Mohanty, A K","year":2019,"journal":"Tropical animal health and production, 51(8), 2493-2503","doi":"10.1007/s11250-019-01958-3","pmid":"31197726","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04067","title":"Venom-Derived Peptide Modulators of Cation-Selective Channels: Friend, Foe or Frenemy.","authors":"Bajaj, Saumya; Han, Jingyao","year":2019,"journal":"Frontiers in pharmacology, 10, 58","doi":"10.3389/fphar.2019.00058","pmid":"30863305","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04068","title":"MiR-21 in Substance P-induced exosomes promotes cell proliferation and migration in human colonic epithelial cells.","authors":"Bakirtzi, Kyriaki; Man Law, Ivy Ka; Fang, Kai; Iliopoulos, Dimitrios; Pothoulakis, Charalabos","year":2019,"journal":"American journal of physiology. Gastrointestinal and liver physiology, 317(6), G802-G810","doi":"10.1152/ajpgi.00043.2019","pmid":"31545921","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04069","title":"The melanocortin pathway and control of appetite-progress and therapeutic implications.","authors":"Baldini, Giulia; Phelan, Kevin D","year":2019,"journal":"The Journal of endocrinology, 241(1), R1-R33","doi":"10.1530/JOE-18-0596","pmid":"30812013","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04070","title":"The 2018 Nobel Prize in Chemistry: phage display of peptides and antibodies.","authors":"Barderas, Rodrigo; Benito-Peña, Elena","year":2019,"journal":"Analytical and bioanalytical chemistry, 411(12), 2475-2479","doi":"10.1007/s00216-019-01714-4","pmid":"30888467","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04071","title":"Development of a novel fluorescent ligand of growth hormone secretagogue receptor based on the N-Terminal Leap2 region.","authors":"Barrile, Franco; M'Kadmi, Céline; De Francesco, Pablo N; Cabral, Agustina; García Romero, Guadalupe; Mustafá, Emilio R; Cantel, Sonia; Damian, Marjorie; Mary, Sophie; Denoyelle, Séverine; Banères, Jean-Louis; Marie, Jacky; Raingo, Jesica; Fehrentz, Jean-Alain; Perelló, Mario","year":2019,"journal":"Molecular and cellular endocrinology, 498, 110573","doi":"10.1016/j.mce.2019.110573","pmid":"31499133","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The fluorescent LEAP2 analogue (F-LEAP2) displayed binding affinity and inverse agonism to GHSR similar to native LEAP2. Notably, F-LEAP2 labeled GHSR on the cell surface, while fluorescent ghrelin was mainly observed inside cells — revealing different receptor trafficking patterns for agonists versus antagonists.\n\nWhen centrally injected in mice, F-LEAP2 reduced ghrelin-induced food intake with efficacy similar to native LEAP2 and specifically labeled cells in GHSR-expressing brain areas. This dual functionality — biological activity plus fluorescent visualization — makes F-LEAP2 a uniquely valuable research tool.","whyItMatters":"The ghrelin system is a prime target for appetite-suppressing drugs, but studying it has been limited by a lack of good visualization tools. F-LEAP2 solves this by letting researchers see exactly where ghrelin receptors are and how they behave when blocked — critical information for developing anti-obesity drugs that target ghrelin signaling. The observation that LEAP2 and ghrelin cause different receptor trafficking could reveal new pharmacological strategies.","specificNumbers":"","methodology":"Researchers synthesized F-LEAP2 based on the N-terminal LEAP2 sequence conjugated to a fluorescent tag. In vitro binding affinity and inverse agonism were assessed in GHSR-expressing cell lines. Cell surface versus intracellular labeling patterns were compared between F-LEAP2 and fluorescent ghrelin. In vivo studies in C57BL/6 mice tested F-LEAP2's ability to block ghrelin-induced food intake and label GHSR-expressing brain regions following central (intracerebroventricular) injection.","limitations":"F-LEAP2 was injected centrally (directly into the brain) rather than peripherally, so its ability to cross the blood-brain barrier is unknown. The fluorescent tag could potentially alter peptide behavior in contexts not tested. Only acute effects on food intake were measured, not chronic appetite regulation. The tool's utility is primarily for research rather than therapeutic application."},{"rthcId":"RPEP-04072","title":"Diselenolane-Mediated Cellular Uptake: Efficient Cytosolic Delivery of Probes, Peptides, Proteins, Artificial Metalloenzymes and Protein-Coated Quantum Dots.","authors":"Bartolami, Eline; Basagiannis, Dimitris; Zong, Lili; Martinent, Rémi; Okamoto, Yasunori; Laurent, Quentin; Ward, Thomas R; Gonzalez-Gaitan, Marcos; Sakai, Naomi; Matile, Stefan","year":2019,"journal":"Chemistry (Weinheim an der Bergstrasse, Germany), 25(16), 4047-4051","doi":"10.1002/chem.201805900","pmid":"30815941","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04073","title":"Endothelin: 30 Years From Discovery to Therapy.","authors":"Barton, Matthias; Yanagisawa, Masashi","year":2019,"journal":"Hypertension (Dallas, Tex. : 1979), 74(6), 1232-1265","doi":"10.1161/HYPERTENSIONAHA.119.12105","pmid":"31679425","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04074","title":"Oxytocin Selectively Improves Empathic Accuracy: A Replication in Men and Novel Insights in Women.","authors":"Bartz, Jennifer A; Nitschke, Jonas P; Krol, Sonia A; Tellier, Pierre-Paul","year":2019,"journal":"Biological psychiatry. Cognitive neuroscience and neuroimaging, 4(12), 1042-1048","doi":"10.1016/j.bpsc.2019.01.014","pmid":"30954442","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04075","title":"Combined GLP-1, Oxyntomodulin, and Peptide YY Improves Body Weight and Glycemia in Obesity and Prediabetes/Type 2 Diabetes: A Randomized, Single-Blinded, Placebo-Controlled Study.","authors":"Behary, Preeshila; Tharakan, George; Alexiadou, Kleopatra; Johnson, Nicholas; Wewer Albrechtsen, Nicolai J; Kenkre, Julia; Cuenco, Joyceline; Hope, David; Anyiam, Oluwaseun; Choudhury, Sirazum; Alessimii, Haya; Poddar, Ankur; Minnion, James; Doyle, Chedie; Frost, Gary; Le Roux, Carel; Purkayastha, Sanjay; Moorthy, Krishna; Dhillo, Waljit; Holst, Jens J; Ahmed, Ahmed R; Prevost, A Toby; Bloom, Stephen R; Tan, Tricia M","year":2019,"journal":"Diabetes care, 42(8), 1446-1453","doi":"10.2337/dc19-0449","pmid":"31177183","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Four weeks of subcutaneous GOP infusion produced significantly greater weight loss than placebo (-4.4 kg vs -2.5 kg, p=0.025) and substantially greater improvement in fructosamine levels (-44.1 vs -11.7 µmol/L, p=0.0026), a marker of medium-term blood sugar control.\n\nThe most striking finding was the comparison with gastric bypass (RYGB) and very low-calorie diet (VLCD). Despite causing less total weight loss than either comparator, GOP achieved superior glucose tolerance after a mixed meal and reduced glycemic variability on continuous glucose monitoring. This suggests the three-hormone combination has direct glucose-regulating effects independent of weight loss alone.","whyItMatters":"Gastric bypass is the most effective treatment for obesity with diabetes, but it's invasive and irreversible. This study showed that infusing the same hormones the gut produces after bypass surgery can replicate — and even exceed — its glucose control benefits. This provides proof-of-concept for developing drug cocktails that mimic the hormonal effects of bariatric surgery, potentially offering patients the metabolic benefits without the surgical risks.","specificNumbers":"","methodology":"Single-blinded, placebo-controlled randomized study. 26 obese patients with prediabetes or type 2 diabetes were randomized to receive subcutaneous GOP infusion (n=15) or saline placebo (n=11) for 4 weeks. Two unblinded comparator groups were also studied: 21 post-RYGB patients and 22 patients on a very low-calorie diet. Outcomes included body weight, fructosamine levels, glucose and insulin during mixed meal tests, energy expenditure, energy intake, and continuous glucose monitoring.","limitations":"Small sample size (26 randomized patients) limits statistical power. The study was single-blinded, not double-blinded. GOP was delivered by continuous subcutaneous infusion, which isn't practical for long-term clinical use. The RYGB and VLCD comparator groups were unblinded and not randomized, making direct comparisons less reliable. Only 4 weeks of treatment was studied — long-term effects and sustainability are unknown."},{"rthcId":"RPEP-04076","title":"Considerations on the Rational Design of Covalently Conjugated Cell-Penetrating Peptides (CPPs) for Intracellular Delivery of Proteins: A Guide to CPP Selection Using Glucarpidase as the Model Cargo Molecule.","authors":"Behzadipour, Yasaman; Hemmati, Shiva","year":2019,"journal":"Molecules (Basel, Switzerland), 24(23)","doi":"10.3390/molecules24234318","pmid":"31779220","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Researchers developed a systematic bioinformatics workflow for selecting optimal cell-penetrating peptides (CPPs) for covalent conjugation to therapeutic proteins. From 1,155 CPPs, 70 with the highest predicted uptake efficiency were screened. N-terminal conjugation produced significantly higher-quality constructs than C-terminal conjugation (p<0.05). Seventeen CPP conjugates were identified as the most promising based on translational efficacy, thermodynamic stability, aggregation risk, folding rate, flexibility, and protease susceptibility.","whyItMatters":"Getting therapeutic proteins inside cells is one of the biggest challenges in drug delivery. Cell-penetrating peptides can solve this but choosing the wrong CPP can damage the protein's structure and function. This systematic computational guide eliminates trial-and-error, making it faster and cheaper to design effective CPP-protein therapeutics.","specificNumbers":"1,155 CPPs screened · 70 top candidates selected · 17 final promising constructs · N-terminal > C-terminal conjugation (p<0.05)","methodology":"Computational bioinformatics workflow: 70 CPPs with the highest predicted uptake efficiency were selected from a database of 1,155. Each was computationally conjugated to the N- or C-terminus of CPG2 (glucarpidase). Constructs were evaluated for translational efficacy, thermodynamic properties, aggregation probability, folding rate, backbone flexibility, and protease susceptibility. N- vs C-terminal position effects were compared using unpaired t-tests.","limitations":"Entirely computational — no experimental validation of the predicted CPP-protein conjugates was performed. The workflow was demonstrated on a single model protein (CPG2), so generalizability to other cargo proteins is assumed but not proven. Computational predictions of uptake efficiency and stability may not perfectly reflect real-world behavior."},{"rthcId":"RPEP-04077","title":"Targeting self and neo-epitopes with a modular self-adjuvanting cancer vaccine.","authors":"Belnoue, Elodie; Mayol, Jean-François; Carboni, Susanna; Di Berardino Besson, Wilma; Dupuychaffray, Eloise; Nelde, Annika; Stevanovic, Stefan; Santiago-Raber, Marie-Laure; Walker, Paul R; Derouazi, Madiha","year":2019,"journal":"JCI insight, 5(11)","doi":"10.1172/jci.insight.127305","pmid":"31013258","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The chimeric protein vaccine platform generated potent CD4 helper and CD8 cytotoxic T cell responses against model antigens, neoantigens, and self-antigens in mice. It demonstrated high antitumor efficacy across several murine tumor models. A human vaccine candidate designed for colorectal cancer treatment showed safety and immunogenicity in a non-human primate model (cynomolgus macaques). The three-domain design (CPP + multiantigenic domain + TLR agonist) enabled simultaneous antigen-presenting cell activation and antigen cross-presentation.","whyItMatters":"Many cancer vaccines fail because they can't efficiently deliver antigens to immune cells or generate strong enough T cell responses. This platform solves multiple problems simultaneously through its modular design. The cell-penetrating peptide ensures antigen delivery, the multi-antigen approach targets multiple tumor weaknesses, and the built-in adjuvant eliminates formulation complexity. Advancing to non-human primate testing with a human colorectal cancer candidate demonstrates real translational momentum.","specificNumbers":"","methodology":"Researchers engineered a chimeric fusion protein with three domains: cell-penetrating peptide (CPP), multiantigenic domain (Mad) containing MHC-restricted peptide epitopes, and TLR2/4 agonist domain (TLRag). T cell responses were characterized by flow cytometry and functional assays. Antitumor efficacy was tested in multiple murine tumor models. Safety and immunogenicity of a human colorectal cancer vaccine candidate were evaluated in cynomolgus macaques.","limitations":"Preclinical study primarily in mice, with non-human primate data limited to safety and immunogenicity rather than antitumor efficacy. The modular platform's manufacturing complexity at clinical scale is not addressed. Long-term durability of immune responses was not fully characterized. Translation from mouse tumor models to human cancers with different immune landscapes remains uncertain."},{"rthcId":"RPEP-04078","title":"Oxytocin, vasopressin and trust: Associations with aggressive behavior in healthy young males.","authors":"Berends, Youri R; Tulen, Joke H M; Wierdsma, André I; van Pelt, Johannes; Kushner, Steven A; van Marle, Hjalmar J C","year":2019,"journal":"Physiology & behavior, 204, 180-185","doi":"10.1016/j.physbeh.2019.02.027","pmid":"30802507","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04079","title":"Effects of combined GIP and GLP-1 infusion on energy intake, appetite and energy expenditure in overweight/obese individuals: a randomised, crossover study.","authors":"Bergmann, Natasha C; Lund, Asger; Gasbjerg, Lærke S; Meessen, Emma C E; Andersen, Maria M; Bergmann, Sigrid; Hartmann, Bolette; Holst, Jens J; Jessen, Lene; Christensen, Mikkel B; Vilsbøll, Tina; Knop, Filip K","year":2019,"journal":"Diabetologia, 62(4), 665-675","doi":"10.1007/s00125-018-4810-0","pmid":"30683945","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04080","title":"Peptidomic and glycomic profiling of commercial dairy products: identification, quantification and potential bioactivities.","authors":"Bhattacharya, Mrittika; Salcedo, Jaime; Robinson, Randall C; Henrick, Bethany Michele; Barile, Daniela","year":2019,"journal":"NPJ science of food, 3, 4","doi":"10.1038/s41538-019-0037-9","pmid":"31304276","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04081","title":"Engineered Histidine-Enriched Facial Lipopeptides for Enhanced Intracellular Delivery of Functional siRNA to Triple Negative Breast Cancer Cells.","authors":"Biswas, Abhijit; Chakraborty, Kasturee; Dutta, Chiranjit; Mukherjee, Sanchita; Gayen, Paramita; Jan, Somnath; Mallick, Argha Mario; Bhattacharyya, Dhananjay; Sinha Roy, Rituparna","year":2019,"journal":"ACS applied materials & interfaces, 11(5), 4719-4736","doi":"10.1021/acsami.8b13794","pmid":"30628773","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Cyclic and linear peptides with an Arg-DHis-Arg template and two lipidic moieties achieved high intracellular siRNA delivery. The histidine residues enabled pH-dependent endosomal release: hydrogen bonding between Arg and His side chains was stable at physiological pH but dissociated at the lower pH inside endosomes, triggering cargo release.\n\nPeptides with two linoleyl moieties demonstrated ERK1/2 gene silencing in TNBC cells comparable to the commercial reagent HiPerFect. The peptides were protease-resistant and provided serum stability to siRNA. Combination therapy using ERK1/2-silencing siRNA delivered via gramicidin plus doxorubicin was more effective than siRNA monotherapy for TNBC treatment.","whyItMatters":"Triple-negative breast cancer is the most aggressive breast cancer subtype with limited targeted treatment options. RNA-based therapies could specifically silence cancer-driving genes, but delivering fragile siRNA molecules into cells has been a major bottleneck. These engineered lipopeptides solve multiple delivery challenges — membrane penetration, endosomal escape, and serum stability — in one designed molecule.","specificNumbers":"","methodology":"The researchers designed peptide transporters using computational studies and molecular dynamics simulations to optimize the Arg-DHis-Arg template. They synthesized cyclic and linear lipopeptide variants with different lipid modifications (including linoleic acid). They tested siRNA delivery, gene silencing (ERK1/2 knockdown), serum stability, and protease resistance in TNBC cell lines. Combination therapy experiments paired siRNA delivery with doxorubicin.","limitations":"All experiments were conducted in cell culture, not in animal models or patients. The comparison was made to a commercial transfection reagent, not to clinically relevant delivery systems. Toxicity profiles in normal cells and in vivo biodistribution were not reported. The scalability of lipopeptide synthesis for clinical use was not addressed."},{"rthcId":"RPEP-04082","title":"Lugdunin amplifies innate immune responses in the skin in synergy with host- and microbiota-derived factors.","authors":"Bitschar, Katharina; Sauer, Birgit; Focken, Jule; Dehmer, Hanna; Moos, Sonja; Konnerth, Martin; Schilling, Nadine A; Grond, Stephanie; Kalbacher, Hubert; Kurschus, Florian C; Götz, Friedrich; Krismer, Bernhard; Peschel, Andreas; Schittek, Birgit","year":2019,"journal":"Nature communications, 10(1), 2730","doi":"10.1038/s41467-019-10646-7","pmid":"31227691","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04083","title":"A pilot clinical trial testing topical resiquimod and a xenopeptide as immune adjuvants for a melanoma vaccine targeting MART-1.","authors":"Block, Matthew S; Nevala, Wendy K; Pang, Yuan-Ping; Allred, Jacob B; Strand, Carrie; Markovic, Svetomir N","year":2019,"journal":"Melanoma research, 29(4), 420-427","doi":"10.1097/CMR.0000000000000556","pmid":"30520800","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04084","title":"Switching to iGlarLixi Versus Continuing Daily or Weekly GLP-1 RA in Type 2 Diabetes Inadequately Controlled by GLP-1 RA and Oral Antihyperglycemic Therapy: The LixiLan-G Randomized Clinical Trial.","authors":"Blonde, Lawrence; Rosenstock, Julio; Del Prato, Stefano; Henry, Robert; Shehadeh, Naim; Frias, Juan; Niemoeller, Elisabeth; Souhami, Elisabeth; Ji, Chen; Aroda, Vanita R","year":2019,"journal":"Diabetes care, 42(11), 2108-2116","doi":"10.2337/dc19-1357","pmid":"31530665","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04085","title":"Antimicrobial activity and mechanisms of multiple antimicrobial peptides isolated from rockfish Sebastiscus marmoratus.","authors":"Bo, Jun; Yang, Ying; Zheng, Ronghui; Fang, Chao; Jiang, Yulu; Liu, Jie; Chen, Mengyun; Hong, Fukun; Bailey, Christyn; Segner, Helmut; Wang, Kejian","year":2019,"journal":"Fish & shellfish immunology, 93, 1007-1017","doi":"10.1016/j.fsi.2019.08.054","pmid":"31449978","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04086","title":"Selectivity of Antimicrobial Peptides: A Complex Interplay of Multiple Equilibria.","authors":"Bobone, Sara; Stella, Lorenzo","year":2019,"journal":"Advances in experimental medicine and biology, 1117, 175-214","doi":"10.1007/978-981-13-3588-4_11","pmid":"30980359","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04087","title":"Endogenous opioid modulation of food intake and body weight: Implications for opioid influences upon motivation and addiction.","authors":"Bodnar, Richard J","year":2019,"journal":"Peptides, 116, 42-62","doi":"10.1016/j.peptides.2019.04.008","pmid":"31047940","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04088","title":"Predicting peptide presentation by major histocompatibility complex class I: an improved machine learning approach to the immunopeptidome.","authors":"Boehm, Kevin Michael; Bhinder, Bhavneet; Raja, Vijay Joseph; Dephoure, Noah; Elemento, Olivier","year":2019,"journal":"BMC bioinformatics, 20(1), 7","doi":"10.1186/s12859-018-2561-z","pmid":"30611210","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04089","title":"Cubosomes for topical delivery of the antimicrobial peptide LL-37.","authors":"Boge, Lukas; Hallstensson, Karin; Ringstad, Lovisa; Johansson, Jenny; Andersson, Therese; Davoudi, Mina; Larsson, Per Tomas; Mahlapuu, Margit; Håkansson, Joakim; Andersson, Martin","year":2019,"journal":"European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 134, 60-67","doi":"10.1016/j.ejpb.2018.11.009","pmid":"30445164","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04090","title":"The PYY/Y2R-Deficient Mouse Responds Normally to High-Fat Diet and Gastric Bypass Surgery.","authors":"Boland, Brandon; Mumphrey, Michael B; Hao, Zheng; Gill, Benji; Townsend, R Leigh; Yu, Sangho; Münzberg, Heike; Morrison, Christopher D; Trevaskis, James L; Berthoud, Hans-Rudolf","year":2019,"journal":"Nutrients, 11(3)","doi":"10.3390/nu11030585","pmid":"30857366","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04091","title":"Improvements in chemical carriers of proteins and peptides.","authors":"Bolhassani, Azam","year":2019,"journal":"Cell biology international, 43(4), 437-452","doi":"10.1002/cbin.11108","pmid":"30672055","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04092","title":"Exenatide Reverts the High-Fat-Diet-Induced Impairment of BDNF Signaling and Inflammatory Response in an Animal Model of Alzheimer's Disease.","authors":"Bomba, Manuela; Granzotto, Alberto; Castelli, Vanessa; Onofrj, Marco; Lattanzio, Rossano; Cimini, Annamaria; Sensi, Stefano L","year":2019,"journal":"Journal of Alzheimer's disease : JAD, 70(3), 793-810","doi":"10.3233/JAD-190237","pmid":"31256135","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04093","title":"Peptide Oligomerization Memory Effects and Their Impact on the Physical Stability of the GLP-1 Agonist Liraglutide.","authors":"Bothe, Jameson R; Andrews, Alexandra; Smith, Katelyn J; Joyce, Leo A; Krishnamachari, Yogita; Kashi, Sandhya","year":2019,"journal":"Molecular pharmaceutics, 16(5), 2153-2161","doi":"10.1021/acs.molpharmaceut.9b00106","pmid":"30990695","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04094","title":"Hepcidin cDNA evolution in vertebrates.","authors":"Boumaiza, Mohamed; Abidi, Sondes","year":2019,"journal":"Vitamins and hormones, 110, 1-16","doi":"10.1016/bs.vh.2019.01.001","pmid":"30798806","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Hepcidin, a cysteine-rich cationic peptide with four disulfide bridges belonging to the β-defensin family, has been evolutionarily conserved across vertebrates with dual functions in innate immunity and iron homeostasis. Analysis of hepcidin genes from 17 vertebrate species showed that while some species have multiple hepcidin homologs, generally only one copy per species serves as the iron regulator.\n\nThe pigeon (Columba livia) was a notable exception, with hepcidin sequences that deviate from the one-iron-regulator-per-species pattern. This evolutionary analysis highlights the functional diversification of hepcidin genes across the vertebrate lineage.","whyItMatters":"Understanding how hepcidin evolved helps explain why this peptide is so central to iron metabolism and immunity across all vertebrates, including humans. Hepcidin is a major drug target for iron disorders like anemia of chronic disease and hemochromatosis. Knowing which features are conserved across millions of years of evolution highlights the regions most critical for its function — and most promising for therapeutic targeting.","specificNumbers":"","methodology":"Comparative genomic analysis examining hepcidin gene sequences from 17 vertebrate species, combining literature review with searches of public genomic databases. The study focused on molecular evolution patterns, gene duplication events, and functional conservation of hepcidin across species.","limitations":"The analysis was limited to 17 species and relied on available genomic databases, which may have incomplete or poorly annotated sequences for some organisms. The chapter format limits methodological detail. Functional verification of iron-regulatory versus immune roles was inferred from sequence analysis rather than experimental testing in all species."},{"rthcId":"RPEP-04095","title":"Insect Cecropins, Antimicrobial Peptides with Potential Therapeutic Applications.","authors":"Brady, Daniel; Grapputo, Alessandro; Romoli, Ottavia; Sandrelli, Federica","year":2019,"journal":"International journal of molecular sciences, 20(23)","doi":"10.3390/ijms20235862","pmid":"31766730","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"This review consolidates evidence that insect cecropins and their synthetic analogs are effective against multi-drug resistant (MDR) bacteria while showing low toxicity to mammalian cells. Natural cecropins are primarily active against Gram-negative bacteria, while engineered analogs can target both Gram-positive and Gram-negative pathogens. The peptides also exhibit anti-inflammatory properties, and nanotechnology-based delivery methods may overcome their stability and bioavailability limitations.","whyItMatters":"Antibiotic resistance is one of the most serious threats to global health, and the pipeline for new antibiotics has been running dry. Cecropins — peptides that insects have been using to fight bacteria for hundreds of millions of years — offer a fundamentally different mechanism of action than conventional antibiotics, making resistance development less likely. This review maps out how close we are to turning these natural insect defenses into real drugs.","specificNumbers":"","methodology":"This is a narrative review that synthesizes published research on insect cecropins and their synthetic analogs. The authors compiled data on antimicrobial mechanisms, activity spectra against various pathogens including MDR strains, toxicity profiles against mammalian cells, and potential delivery strategies including nanotechnology approaches.","limitations":"As a review, this paper synthesizes existing research rather than generating new experimental data. The translation from promising lab results to clinical drugs remains a major gap — no cecropin-based therapeutic has reached clinical trials in humans. Production costs and stability in the human body remain significant practical hurdles."},{"rthcId":"RPEP-04096","title":"Possible inflammatory pain biomarkers in postamputation pain.","authors":"Buch, Nina Stockfleth; Nikolajsen, Lone; Karlsson, Páll","year":2019,"journal":"Scandinavian journal of pain, 19(3), 623-627","doi":"10.1515/sjpain-2019-0042","pmid":"31031267","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04097","title":"Succinylated Gelatin Improves the Theranostic Potential of Radiolabeled Exendin-4 in Insulinoma Patients.","authors":"Buitinga, Mijke; Jansen, Tom; van der Kroon, Inge; Woliner-van der Weg, Wietske; Boss, Marti; Janssen, Marcel; Aarntzen, Erik; Béhé, Martin; Wild, Damian; Visser, Eric; Brom, Maarten; Gotthardt, Martin","year":2019,"journal":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 60(6), 812-816","doi":"10.2967/jnumed.118.219980","pmid":"30504139","tags":[],"studyType":"clinical (crossover + dosimetry)","evidenceStrength":"moderate","keyFinding":"Succinylated gelatin (Gelofusine) reduced kidney accumulation of the radiolabeled GLP-1 receptor peptide 111In-exendin-4 by 18.1% in humans without affecting pancreatic uptake. In 3 of 10 volunteers, the reduction was sufficient to better distinguish the pancreatic tail from kidney signal on SPECT/CT imaging. Dosimetric calculations from 5 insulinoma patients estimated that tumor radiation doses of 30.3-127.8 Gy could be achieved, potentially increasing to 156.1 Gy with Gelofusine — making peptide receptor radionuclide therapy feasible for GLP-1R-positive insulinomas.","whyItMatters":"Insulinomas (insulin-secreting pancreatic tumors) are often tiny and hard to find. Radiolabeled exendin-4 targets the GLP-1 receptor on these tumors for both imaging and potential radiation therapy. However, the kidneys absorb large amounts of the radioactive peptide, which limits both the diagnostic quality (kidney signal obscures the nearby pancreas) and therapeutic potential (kidney radiation toxicity limits the dose). Reducing kidney uptake with Gelofusine is a practical solution that improves both diagnosis and opens the door to targeted radiation therapy for these tumors.","specificNumbers":"n=10 healthy volunteers · 18.1% kidney uptake reduction · Pancreatic uptake unchanged · 5 insulinoma patients for dosimetry · Tumor dose 30.3-127.8 Gy · Up to 156.1 Gy with Gelofusine","methodology":"Crossover study: 10 healthy volunteers received 50 MBq of 111In-exendin-4 with either Gelofusine or saline, then switched 3 weeks later. SPECT/CT images were acquired at 24 hours. Kidney and pancreatic uptake were quantified by region-of-interest analysis. Dosimetric calculations were performed using planar scintigraphy data from 5 insulinoma patients to estimate maximum achievable tumor radiation doses with and without Gelofusine.","limitations":"The 18.1% kidney reduction, while statistically significant, is relatively modest — in only 3 of 10 subjects did it meaningfully improve pancreatic visualization. The dosimetric calculations are theoretical estimates based on 5 insulinoma patients, not actual therapeutic outcomes. The study used 111In labeling (for imaging), but therapeutic applications would require different radioisotopes (like 177Lu or 90Y), which may have different kidney kinetics. The healthy volunteer kidney data may not perfectly predict behavior in patients with tumors."},{"rthcId":"RPEP-04098","title":"Ghrelin-Mediated Hippocampal Neurogenesis: Implications for Health and Disease.","authors":"Buntwal, Luke; Sassi, Martina; Morgan, Alwena H; Andrews, Zane B; Davies, Jeffrey S","year":2019,"journal":"Trends in endocrinology and metabolism: TEM, 30(11), 844-859","doi":"10.1016/j.tem.2019.07.001","pmid":"31445747","tags":["neuropeptides","neurogenesis"],"studyType":"review","evidenceStrength":"n/a-review","keyFinding":"Ghrelin, the hunger hormone released by the stomach during food restriction, promotes the growth of new neurons in the hippocampus — the brain's memory center. This review synthesizes accumulating evidence that ghrelin provides a biological link between nutritional status and brain function, specifically by stimulating adult hippocampal neurogenesis.\n\nThe review also highlights that disrupted neurogenesis is connected to cognitive decline in aging and neurodegenerative disease, positioning ghrelin as a potential protective factor for brain health when it's properly regulated.","whyItMatters":"The connection between diet, fasting, and brain health has been observed for decades, but the biological mechanism wasn't clear. This review argues that ghrelin is a key link — when you're in a calorie-restricted state and ghrelin rises, it doesn't just make you hungry; it also stimulates your brain to grow new neurons. This has major implications for understanding why caloric restriction seems to protect against cognitive decline and neurodegeneration.","specificNumbers":"Published in Trends in Endocrinology and Metabolism (IF ~12) · Reviews evidence across animal and human studies · Focus: hippocampal neurogenesis and memory","methodology":"This is a narrative review published in a high-impact endocrinology journal. It synthesizes evidence from animal studies, cellular research, and clinical observations to build the case for ghrelin as a regulator of adult neurogenesis and cognitive function.","limitations":"As a review, no new experimental data is presented. Much of the evidence for ghrelin's neurogenic effects comes from animal models, and direct evidence of ghrelin-stimulated neurogenesis in humans remains limited. The review may emphasize positive findings over null or contradictory results."},{"rthcId":"RPEP-04099","title":"Bladder-Drained Pancreas Transplantation: Urothelial Innate Defenses and Urinary Track Infection Susceptibility.","authors":"Byrne, Matthew; Singh, Aminder; Mowbray, Catherine A; Aldridge, Phillip D; Drage, Lauren K L; Ali, Ased S M; Bates, Lucy; Hall, Judith; Wilson, Colin","year":2019,"journal":"The Journal of surgical research, 235, 288-297","doi":"10.1016/j.jss.2018.09.028","pmid":"30691808","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Bladder-drained (BD) transplant patients had significantly higher urine pH than enteric-drained (ED) patients (7.2 vs. 6.7; P=0.012). BD patients showed significantly decreased urinary lipocalin-2 compared to pre-transplant diabetics (P significant). In vitro, pancreatic enzymes (pancreatin at >12,500 amylase units) directly degraded β-defensin 2, eliminating its antimicrobial activity. The elevated pH from pancreatic secretions further impaired defense peptide function and promoted E. coli growth.","whyItMatters":"Recurrent UTIs are a major complication of bladder-drained pancreas transplants, significantly impacting patient quality of life and sometimes leading to surgical conversion to enteric drainage. This study identifies the specific mechanism — destruction of antimicrobial defense peptides — providing a rational basis for clinical decision-making about drainage technique and potentially informing new approaches to UTI prevention in these patients.","specificNumbers":"","methodology":"Combined retrospective clinical review and in vitro study. Patient records from BD and ED pancreas transplant recipients were reviewed for UTI history. Urine samples were analyzed for pH, β-defensin 2 (HBD2), lipocalin-2, and amylase. In vitro experiments used bacterial growth curves and antimicrobial assays to test the effects of pH, HBD2, and HBD2 plus pancreatin on uropathogenic E. coli survival.","limitations":"The clinical component is retrospective with a relatively small cohort. The in vitro experiments may not fully replicate the complex bladder environment. The study focused on two defense peptides, but other innate defense mechanisms may also be affected. The threshold of amylase units needed to destroy HBD2 (>12,500) may vary in vivo. Long-term outcomes comparing BD and ED drainage were not fully assessed in this study."},{"rthcId":"RPEP-04100","title":"Are melanocortin peptides future therapeutics for cutaneous wound healing?","authors":"Böhm, Markus; Luger, Thomas","year":2019,"journal":"Experimental dermatology, 28(3), 219-224","doi":"10.1111/exd.13887","pmid":"30661264","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04101","title":"Antibacterial and antifungal activity of defensins from the Australian paralysis tick, Ixodes holocyclus.","authors":"Cabezas-Cruz, Alejandro; Tonk, Miray; Bleackley, Mark R; Valdés, James J; Barrero, Roberto A; Hernández-Jarguín, Angélica; Moutailler, Sara; Vilcinskas, Andreas; Richard-Forget, Florence; Anderson, Marilyn A; Rodriguez-Valle, Manuel","year":2019,"journal":"Ticks and tick-borne diseases, 10(6), 101269","doi":"10.1016/j.ttbdis.2019.101269","pmid":"31445875","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Five unique defensin sequences (holosins 1-5) were identified from the I. holocyclus transcriptome, all sharing conserved molecular features with other tick defensins including the γ-core motif.\n\nAntimicrobial testing showed:\n- Holosins 2 and 3 were very active against Gram-positive bacteria S. aureus and Listeria grayi\n- Holosins 2 and 3 also killed the fungus Fusarium graminearum and yeast Candida albicans, with 5 µM sufficient to abrogate growth\n- Synthetic γ-cores (HoloTickCores 1-4) generally showed lower activity than mature defensins\n- Exception: HoloTickCore 2 had activity comparable to mature holosin 2 against the Gram-negative bacterium E. coli\n\nThis reveals a multigene defensin family in I. holocyclus with broad-spectrum antimicrobial activity.","whyItMatters":"As antibiotic resistance grows, finding new antimicrobial compounds is urgent. Ticks survive in pathogen-rich environments thanks partly to their defensin peptides, making them a rich source of potential new antimicrobials. These tick-derived peptides with broad-spectrum activity against bacteria and fungi could inspire next-generation anti-infective drugs.","specificNumbers":"","methodology":"The I. holocyclus transcriptome was searched bioinformatically for defensin sequences. Five unique sequences were identified and characterized. Holosins 2 and 3 and the predicted γ-core peptides (HoloTickCores 1-4) were synthesized and tested for antimicrobial activity against Gram-positive bacteria (S. aureus, L. grayi), Gram-negative bacteria (E. coli), fungus (F. graminearum), and yeast (C. albicans).","limitations":"Only holosins 2 and 3 were fully tested as mature peptides; the antimicrobial profiles of holosins 1, 4, and 5 remain incomplete. All testing was in vitro — no animal or human toxicity or efficacy studies were conducted. The mechanisms of action beyond membrane disruption were not fully characterized. Stability and bioavailability of these peptides are unknown."},{"rthcId":"RPEP-04102","title":"Structure-Function and Therapeutic Potential of Spider Venom-Derived Cysteine Knot Peptides Targeting Sodium Channels.","authors":"Cardoso, Fernanda C; Lewis, Richard J","year":2019,"journal":"Frontiers in pharmacology, 10, 366","doi":"10.3389/fphar.2019.00366","pmid":"31031623","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Spider venom-derived cysteine knot peptides modulate voltage-gated sodium channels (NaV) by binding to structural domains outside the channel pore, allosterically promoting either opening or closing. This mechanism produces diverse effects including modified pain responses, muscle paralysis, cardiac arrest, and numbness.\n\nCritically, some of these peptides show subtype selectivity — they can distinguish between different NaV subtypes. This is therapeutically important because specific NaV subtypes (like NaV1.7 for pain, NaV1.1 for epilepsy) are implicated in different disorders. Subtype-selective spider venom peptides could theoretically target disease-relevant channels while sparing others, avoiding the broad side effects of current sodium channel drugs.","whyItMatters":"Current sodium channel-blocking drugs (like those used for pain and epilepsy) typically lack subtype selectivity, causing side effects by hitting multiple channel types throughout the body. Spider venom peptides have evolved over millions of years to target sodium channels with remarkable precision. Understanding their structure-activity relationships could enable the design of highly selective drugs for chronic pain, epilepsy, and other neurological conditions where current treatments fall short.","specificNumbers":"","methodology":"This is a review article that examines published research on the structure-activity relationships of spider venom cysteine knot peptides. The authors synthesize structural biology data (how the peptides fold and bind), electrophysiology studies (how they affect channel function), and pharmacological studies (their effects in disease models) to assess therapeutic potential.","limitations":"As a review article, this paper does not present new experimental data. Most of the therapeutic potential discussed is based on preclinical studies, with very few spider venom peptides having advanced to clinical trials at the time of publication. The challenges of peptide drug delivery (most require injection), stability, and manufacturing costs are acknowledged but not deeply explored. Selectivity profiles of many discussed peptides remain incomplete."},{"rthcId":"RPEP-04103","title":"Preclinical Testing in Translational Animal Models of Prader-Willi Syndrome: Overview and Gap Analysis.","authors":"Carias, K Vanessa; Wevrick, Rachel","year":2019,"journal":"Molecular therapy. Methods & clinical development, 13, 344-358","doi":"10.1016/j.omtm.2019.03.001","pmid":"30989085","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04104","title":"Sea snake cathelicidin (Hc-cath) exerts a protective effect in mouse models of lung inflammation and infection.","authors":"Carlile, Simon R; Shiels, Jenna; Kerrigan, Lauren; Delaney, Rebecca; Megaw, Julianne; Gilmore, Brendan F; Weldon, Sinéad; Dalton, John P; Taggart, Clifford C","year":2019,"journal":"Scientific reports, 9(1), 6071","doi":"10.1038/s41598-019-42537-8","pmid":"30988402","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04105","title":"Candida albicans-Cell Interactions Activate Innate Immune Defense in Human Palate Epithelial Primary Cells via Nitric Oxide (NO) and β-Defensin 2 (hBD-2).","authors":"Casaroto, Ana Regina; da Silva, Rafaela Alves; Salmeron, Samira; Rezende, Maria Lúcia Rubo de; Dionísio, Thiago José; Santos, Carlos Ferreira Dos; Pinke, Karen Henriette; Klingbeil, Maria Fátima Guarizo; Salomão, Priscila Aranda; Lopes, Marcelo Milanda Ribeiro; Lara, Vanessa Soares","year":2019,"journal":"Cells, 8(7)","doi":"10.3390/cells8070707","pmid":"31336838","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04106","title":"Quantitative assessment of oligomeric amyloid β peptide binding to α7 nicotinic receptor.","authors":"Cecon, Erika; Dam, Julie; Luka, Marine; Gautier, Clément; Chollet, Anne-Marie; Delagrange, Philippe; Danober, Laurence; Jockers, Ralf","year":2019,"journal":"British journal of pharmacology, 176(18), 3475-3488","doi":"10.1111/bph.14688","pmid":"30981214","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04107","title":"Acylated and unacylated ghrelin directly regulate ß-3 stimulated lipid turnover in rodent subcutaneous and visceral adipose tissue ex vivo but not in vivo.","authors":"Cervone, Daniel T; Sheremeta, Justin; Kraft, Emily N; Dyck, David J","year":2019,"journal":"Adipocyte, 8(1), 1-15","doi":"10.1080/21623945.2018.1528811","pmid":"30265180","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04108","title":"Recent Advances in Pharmacotherapy for Episodic Migraine.","authors":"Chan, Calvin; Goadsby, Peter J","year":2019,"journal":"CNS drugs, 33(11), 1053-1071","doi":"10.1007/s40263-019-00665-9","pmid":"31556018","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04109","title":"Ion Channels Involved in Substance P-Mediated Nociception and Antinociception.","authors":"Chang, Chu-Ting; Jiang, Bo-Yang; Chen, Chih-Cheng","year":2019,"journal":"International journal of molecular sciences, 20(7)","doi":"10.3390/ijms20071596","pmid":"30935032","tags":[],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Substance P, an 11-amino-acid neuropeptide long assumed to only cause pain, actually plays a paradoxical dual role — it can both promote pain (nociception) and suppress it (anti-nociception). The direction of its effect depends on which ion channels it modulates and which cell types express the NK1 receptor.\n\nThe review maps how SP activates different downstream signaling pathways through NK1 receptors in different cell types, engaging calcium channels, potassium channels, and other ion channels to produce opposite pain outcomes. This dual nature suggests that targeting the anti-nociceptive SP-NK1R pathway could lead to a new class of painkillers.","whyItMatters":"Pain management remains one of the biggest challenges in medicine, with opioid alternatives urgently needed. If substance P — one of the most studied neuropeptides — can actually suppress pain under certain conditions, understanding exactly how could open an entirely new approach to analgesic drug design based on channeling SP's anti-pain pathway rather than blocking it entirely.","specificNumbers":"11 amino acids (substance P length) · NK1R receptor · Calcium and potassium channels involved · Review of both pro-pain and anti-pain pathways","methodology":"This is a narrative review of published studies examining substance P's role in pain signaling. The authors analyzed evidence on SP-modulated ion channels (calcium, potassium, and others), NK1 receptor signaling in different cell types, and the differential downstream effector systems that determine whether SP produces pain or pain relief.","limitations":"As a narrative review, this paper synthesizes existing literature without new experimental data. Much of the anti-nociceptive evidence comes from animal models, and the conditions under which SP suppresses vs. promotes pain in humans are not yet fully defined. The clinical translatability of the anti-nociceptive pathway remains theoretical."},{"rthcId":"RPEP-04110","title":"Using backbone-cyclized Cys-rich polypeptides as molecular scaffolds to target protein-protein interactions.","authors":"Chaudhuri, Dipankar; Aboye, Teshome; Camarero, Julio A","year":2019,"journal":"The Biochemical journal, 476(1), 67-83","doi":"10.1042/BCJ20180792","pmid":"30635453","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Backbone-cyclized, cysteine-rich polypeptides — including cyclotides, θ-defensins, and sunflower trypsin inhibitor peptides — serve as exceptionally stable molecular scaffolds for designing new drugs and bioimaging tools. These cyclic peptides are far more resistant to chemical, thermal, and biological degradation than linear peptides. They tolerate extensive sequence modification while maintaining structure, can cross cell membranes, and can modulate intracellular protein-protein interactions both in vitro and in vivo.","whyItMatters":"Traditional peptide drugs break down quickly in the body and can't enter cells. Backbone-cyclized peptides overcome both limitations — their circular structure with disulfide bonds makes them nearly indestructible, and many can cross cell membranes to reach intracellular targets. This makes them ideal starting points for designing drugs that target protein-protein interactions, which are notoriously difficult to block with conventional small-molecule drugs.","specificNumbers":"Review covers cyclotides, θ-defensins, and sunflower trypsin inhibitor (SFTI) peptides · enhanced chemical, thermal, and biological stability · cell membrane permeability · tolerance to sequence variability","methodology":"This is a review article providing an overview of recent developments in using three classes of disulfide-rich, backbone-cyclized polypeptides (cyclotides, θ-defensins, and sunflower trypsin inhibitor peptides) as molecular scaffolds for drug design and bioimaging applications.","limitations":"As a review, no new experimental data are presented. While these scaffolds show promise in preclinical studies, few backbone-cyclized peptide drugs have advanced to clinical trials. Manufacturing scalability and cost for complex cyclic peptides remain challenges. The review does not address potential immunogenicity concerns with therapeutic use."},{"rthcId":"RPEP-04111","title":"Predicting HLA class II antigen presentation through integrated deep learning.","authors":"Chen, Binbin; Khodadoust, Michael S; Olsson, Niclas; Wagar, Lisa E; Fast, Ethan; Liu, Chih Long; Muftuoglu, Yagmur; Sworder, Brian J; Diehn, Maximilian; Levy, Ronald; Davis, Mark M; Elias, Joshua E; Altman, Russ B; Alizadeh, Ash A","year":2019,"journal":"Nature biotechnology, 37(11), 1332-1343","doi":"10.1038/s41587-019-0280-2","pmid":"31611695","tags":["computational","peptide-vaccines"],"studyType":"computational-study","evidenceStrength":"high","keyFinding":"Researchers developed MARIA, a deep learning system that predicts which peptides will be presented by HLA class II molecules to trigger immune responses. Unlike previous tools that relied only on binding data, MARIA integrates four types of information: binding measurements, mass spectrometry-identified peptide-HLA sequences, gene expression levels, and protease cleavage patterns.\n\nMARIA achieved an AUC of 0.89–0.92, significantly outperforming existing prediction methods. When validated against independent cancer studies, peptides scored high by MARIA were more likely to trigger strong CD4+ T cell responses.\n\nThe tool can identify immunogenic epitopes for both cancer immunotherapy (neoantigens) and autoimmune disease research.","whyItMatters":"Predicting which peptide fragments the immune system will recognize is the fundamental challenge in designing cancer vaccines and immunotherapies. HLA class II presentation to CD4+ T cells is critical for sustained immune responses but has been much harder to predict than HLA class I. MARIA's superior accuracy — published in Nature Biotechnology — could accelerate personalized cancer vaccine development by identifying the most promising peptide targets from a patient's tumor.","specificNumbers":"AUC 0.89–0.92 · Outperformed existing methods · Trained on 4 data modalities · Validated across independent cancer neoantigen studies","methodology":"Developed a multimodal recurrent neural network (MARIA) trained on: (1) in vitro HLA binding measurements, (2) mass spectrometry-identified peptide-HLA ligand sequences, (3) antigen gene expression levels, and (4) protease cleavage signatures. Performance evaluated on validation datasets and independently validated against published cancer neoantigen studies measuring CD4+ T cell responses.","limitations":"Prediction accuracy, while best-in-class, is not perfect (AUC 0.89–0.92). Performance may vary across less common HLA alleles with fewer training examples. The tool predicts antigen presentation, not guaranteed immune response — other factors affect whether a presented peptide actually triggers effective immunity. Computational predictions always require experimental validation."},{"rthcId":"RPEP-04112","title":"Thalidomide ameliorates rosacea-like skin inflammation and suppresses NF-κB activation in keratinocytes.","authors":"Chen, Mengting; Xie, Hongfu; Chen, Zhaohui; Xu, San; Wang, Ben; Peng, Qinqin; Sha, Ke; Xiao, Wenqin; Liu, Tangxiele; Zhang, Yiya; Li, Ji; Deng, Zhili","year":2019,"journal":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 116, 109011","doi":"10.1016/j.biopha.2019.109011","pmid":"31132668","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04113","title":"Inhibition of microRNA-34a mediates protection of thymosin beta 4 in endothelial progenitor cells against advanced glycation endproducts by targeting B-cell lymphoma 2.","authors":"Chen, Qi; Shen, Zhida; Mao, Yanjun; Li, Qinfeng; Liu, Yu; Mei, Menghan; Qiu, Fuyu; Wang, Meihui","year":2019,"journal":"Canadian journal of physiology and pharmacology, 97(10), 945-951","doi":"10.1139/cjpp-2018-0743","pmid":"31397599","tags":["thymosin-beta-4"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Thymosin beta 4 protected endothelial progenitor cells (EPCs) from damage caused by advanced glycation endproducts (AGEs) — toxic compounds that accumulate in diabetes. The mechanism works through a specific molecular pathway: thymosin beta 4 suppresses microRNA-34a, which in turn allows the anti-apoptotic protein Bcl-2 to remain active. When microRNA-34a was artificially increased or Bcl-2 was knocked down, the protective effect of thymosin beta 4 was abolished, confirming this pathway is essential.\n\nThe protection manifested as improved cell survival, reduced programmed cell death (apoptosis), lower oxidative stress, and better mitochondrial function.","whyItMatters":"Diabetes damages blood vessels partly through AGEs, which destroy the progenitor cells needed for vascular repair. If thymosin beta 4 can protect these repair cells, it could potentially slow or prevent diabetic vascular complications — a major cause of blindness, kidney failure, and amputations in diabetic patients.","specificNumbers":"","methodology":"In vitro cell culture study using human endothelial progenitor cells isolated from healthy volunteers. Cells were exposed to advanced glycation endproducts (AGEs) and treated with thymosin beta 4. MicroRNA-34a levels were manipulated using inhibitors and mimics. Bcl-2 was knocked down using siRNA. Outcomes measured included cell viability, apoptosis, oxidative stress markers, and mitochondrial function.","limitations":"This is entirely an in vitro study — cells in a dish, not in a living organism. The concentrations of thymosin beta 4 and AGEs used may not reflect physiological conditions. EPCs from healthy volunteers may behave differently from those of diabetic patients. No animal or human efficacy data is provided."},{"rthcId":"RPEP-04114","title":"Identification and characterization of three novel antimicrobial peptides from Acipenser dabryanus.","authors":"Chen, Yeyu; Gong, Quan; Song, Mingjiang; Lai, Jiansheng; Sun, Jiahua; Liu, Ya","year":2019,"journal":"Fish & shellfish immunology, 88, 207-216","doi":"10.1016/j.fsi.2019.02.050","pmid":"30807859","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04115","title":"Design and antimicrobial activities of LL-37 derivatives inhibiting the formation of Streptococcus mutans biofilm.","authors":"Chen, Zhao; Yang, Guang; Lu, Shengsheng; Chen, Daiwei; Fan, Sheng; Xu, Junyang; Wu, Buling; He, Jian","year":2019,"journal":"Chemical biology & drug design, 93(6), 1175-1185","doi":"10.1111/cbdd.13419","pmid":"30635992","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04116","title":"A Self-Delivery Chimeric Peptide for Photodynamic Therapy Amplified Immunotherapy.","authors":"Cheng, Hong; Fan, Gui-Ling; Fan, Jing-Hao; Zheng, Rong-Rong; Zhao, Lin-Ping; Yuan, Ping; Zhao, Xiao-Ya; Yu, Xi-Yong; Li, Shi-Ying","year":2019,"journal":"Macromolecular bioscience, 19(4), e1800410","doi":"10.1002/mabi.201800410","pmid":"30576082","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04117","title":"Delivery of Antigen to CD8+ Dendritic Cells by Fusing Antigen With Formyl Peptide Receptor-Like 1 Inhibitor Protein Induces Antitumor Immunity.","authors":"Chiang, Chen-Yi; Wu, Chiao-Chieh; Chen, Yi-Jyun; Liu, Shih-Jen; Leng, Chih-Hsiang; Chen, Hsin-Wei","year":2019,"journal":"Frontiers in immunology, 10, 1839","doi":"10.3389/fimmu.2019.01839","pmid":"31428106","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04118","title":"The immunotherapeutic effects of recombinant Bacillus Calmette-Guérin resistant to antimicrobial peptides on bladder cancer cells.","authors":"Cho, Min-Ji; Kim, Myeong Joo; Kim, Kijeong; Choi, Young Wook; Lee, Sang-Jin; Whang, Young Mi; Chang, In Ho","year":2019,"journal":"Biochemical and biophysical research communications, 509(1), 167-174","doi":"10.1016/j.bbrc.2018.12.097","pmid":"30579607","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04119","title":"Botulinum toxin blocks mast cells and prevents rosacea like inflammation.","authors":"Choi, Jae Eun; Werbel, Tyler; Wang, Zhenping; Wu, Chia Chi; Yaksh, Tony L; Di Nardo, Anna","year":2019,"journal":"Journal of dermatological science, 93(1), 58-64","doi":"10.1016/j.jdermsci.2018.12.004","pmid":"30658871","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Botulinum toxin A and B directly inhibited mast cell degranulation in both human and mouse mast cells. The mechanism involves cleaving SNAP-25 (toxin A) and VAMP2 (toxin B), which are essential for the vesicle fusion machinery that mast cells use to release inflammatory mediators. Mouse mast cells express the botulinum toxin receptor Sv2, confirming they are direct targets. In a mouse rosacea model using LL-37 (the antimicrobial peptide linked to rosacea), botulinum toxin A pretreatment significantly reduced skin redness, mast cell degranulation, and expression of rosacea biomarkers.","whyItMatters":"Rosacea is a chronic skin condition affecting millions, and severe cases resist standard treatments. Clinical observations had shown that botulinum toxin injections help, but no one understood why. This study reveals the mechanism — botulinum toxin directly blocks mast cells from releasing inflammatory mediators, connecting two peptide pathways (botulinum toxin and cathelicidin LL-37) in rosacea biology.","specificNumbers":"Both toxin A and B inhibited mast cell degranulation · Sv2 receptor confirmed on mast cells · SNAP-25 cleaved by toxin A · VAMP2 reduced by toxin B · LL-37-induced rosacea biomarkers reduced in vivo","methodology":"Combined in vitro and in vivo study. Human and mouse primary mast cells were pretreated with botulinum toxin A or B and stimulated with compound 48/80 to measure degranulation. Sv2 receptor expression was confirmed by qPCR. SNAP-25 and VAMP2 were visualized by immunofluorescence. In vivo rosacea model: LL-37 was injected intradermally in mice with or without botulinum toxin A pretreatment. Skin redness, mast cell counts, and rosacea biomarker mRNA were measured.","limitations":"Mouse model of rosacea using LL-37 injection may not fully replicate the complex, chronic nature of human rosacea. The study did not assess long-term outcomes or optimal dosing for clinical use. The in vitro degranulation assay used compound 48/80 rather than the physiological LL-37 trigger, though the in vivo model addressed this gap."},{"rthcId":"RPEP-04120","title":"Targeted hippocampal GABA neuron ablation by Stable Substance P-saporin causes hippocampal sclerosis and chronic epilepsy in rats.","authors":"Chun, Eugene; Bumanglag, Argyle V; Burke, Sara N; Sloviter, Robert S","year":2019,"journal":"Epilepsia, 60(5), e52-e57","doi":"10.1111/epi.14723","pmid":"30963545","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04121","title":"Treatment of Pulmonary Hypertension With Angiotensin II Receptor Blocker and Neprilysin Inhibitor Sacubitril/Valsartan.","authors":"Clements, Richard T; Vang, Alexander; Fernandez-Nicolas, Ana; Kue, Nouaying R; Mancini, Thomas J; Morrison, Alan R; Mallem, Krishna; McCullough, Danielle J; Choudhary, Gaurav","year":2019,"journal":"Circulation. Heart failure, 12(11), e005819","doi":"10.1161/CIRCHEARTFAILURE.119.005819","pmid":"31707802","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In rats with SU5416/hypoxia-induced pulmonary hypertension, six weeks of sacubitril/valsartan treatment significantly reduced right ventricular systolic pressure (62±4 vs 46±5 mmHg), right ventricular hypertrophy (RV/LV+S ratio: 0.74±0.06 vs 0.46±0.06), and myocardial collagen content (8.2±0.3 vs 6.4±0.4 µg/50 µg protein) compared to placebo.\n\nRight ventricular contractility also improved (31.2±1.8 vs 43.1±3.6 mm/s). Valsartan alone did not achieve these improvements. The combination treatment increased lung levels of ANP, BNP, and cGMP while decreasing plasma endothelin-1, and reduced pulmonary vascular wall thickness — indicating benefits to both the heart and the lung vasculature.","whyItMatters":"Pulmonary hypertension remains difficult to treat, and the right ventricle's response to it is a major driver of patient outcomes. Sacubitril/valsartan (marketed as Entresto) is already widely used for left-sided heart failure. This study suggests it could potentially be repurposed for pulmonary hypertension by leveraging its unique dual mechanism — blocking angiotensin while simultaneously preserving natriuretic peptides that naturally dilate lung blood vessels.","specificNumbers":"","methodology":"Pulmonary hypertension was induced in Sprague-Dawley rats using the SU5416/hypoxia model. Animals were divided into four groups: normoxic controls (n=18), PH with placebo (n=34), PH with sacubitril/valsartan (n=24), and PH with valsartan alone (n=16). Treatment lasted six weeks. Outcomes included right ventricular pressure, hypertrophy index, collagen content, contractility, pulmonary vascular wall thickness, natriuretic peptide levels, and PKC isozyme expression.","limitations":"This is an animal study using a specific rat model (SU5416/hypoxia) that mimics some but not all features of human pulmonary arterial hypertension. The six-week treatment duration may not capture long-term effects. Group sizes were unequal (16–34 per group). Results in rats may not translate directly to humans due to differences in drug metabolism, hemodynamics, and disease complexity. The study did not assess survival outcomes."},{"rthcId":"RPEP-04122","title":"Overexpressing ovotransferrin and avian β-defensin-3 improves antimicrobial capacity of chickens and poultry products.","authors":"Cooper, Caitlin A; Tizard, Mark L; Stanborough, Tamsyn; Moore, Sean C; Chandry, P Scott; Jenkins, Kristie A; Wise, Terry G; O'Neil, Terri E; Layton, Daniel S; Morris, Kirsten R; Moore, Robert J; Fegan, Narelle; Doran, Timothy J","year":2019,"journal":"Transgenic research, 28(1), 51-76","doi":"10.1007/s11248-018-0101-2","pmid":"30374651","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Transgenic chickens overexpressing ovotransferrin or avian β-defensin-3 (AvβD3) showed antimicrobial peptide expression in egg white, breast muscle, and serum at both RNA and protein levels.\n\nThe antimicrobial effects were substantial: transgene expression significantly reduced growth of aerobic bacteria and coliforms in breast muscle, and decreased Salmonella enterica growth in egg white. The peptides inhibited growth of both human and chicken bacterial pathogens as well as spoilage bacteria in vitro.\n\nBeyond the direct antimicrobial effects, the transgenic birds also showed changes to their immune systems, including increased proportions of CD8+ T cells in blood — suggesting the overexpressed peptides also boosted innate immunity.","whyItMatters":"Foodborne illness from poultry products — especially Salmonella — sickens millions of people annually. This study demonstrates a fundamentally different approach: rather than treating contamination after the fact, antimicrobial peptides are produced by the chickens themselves, reducing pathogens in meat and eggs from the start. It also shows defensins can modulate the birds' immune systems, providing a dual benefit.","specificNumbers":"","methodology":"Researchers used Tol-2 transposon technology to genetically modify chickens to overexpress either ovotransferrin or avian β-defensin-3. They confirmed transgene expression at the RNA and protein level across multiple tissues. Antimicrobial activity was tested in vitro against various bacterial pathogens. Immune cell populations in blood, bursa, and spleen were analyzed by flow cytometry.","limitations":"This study used genetically modified chickens, which face significant regulatory and public acceptance barriers in most countries. The antimicrobial testing was primarily done in vitro, and real-world food production conditions may differ. Long-term effects of peptide overexpression on chicken health, welfare, and production performance were not fully characterized. Whether bacteria could develop resistance to these overexpressed peptides over time was not addressed."},{"rthcId":"RPEP-04123","title":"Fecal human β-defensin-2 (hBD-2) levels and gut microbiota patterns in preterm neonates with different feeding patterns.","authors":"Corebima, Brigitta I R V; Rohsiswatmo, Rinawati; Gayatri, Pramita; Patole, Sanjay","year":2019,"journal":"Iranian journal of microbiology, 11(2), 151-159","doi":null,"pmid":"31341570","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04124","title":"Growth hormone secretagogue receptor signalling affects high-fat intake independently of plasma levels of ghrelin and LEAP2, in a 4-day binge eating model.","authors":"Cornejo, María Paula; Castrogiovanni, Daniel; Schiöth, Helgi B; Reynaldo, Mirta; Marie, Jacky; Fehrentz, Jean-Alain; Perello, Mario","year":2019,"journal":"Journal of neuroendocrinology, 31(10), e12785","doi":"10.1111/jne.12785","pmid":"31469195","tags":["ghrelin-and-growth-hormone-secretagogues"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"The ghrelin receptor (GHSR) in the brain drives binge-like high-fat eating in mice independently of ghrelin itself. Plasma levels of ghrelin and its natural blocker LEAP2 didn't change during binge eating, and injecting ghrelin systemically didn't alter binge behavior. However, blocking the receptor's constitutive (always-on) activity in the brain — using either LEAP2 or a synthetic blocker (K-(D-1-Nal)-FwLL-NH2) delivered directly to the brain — reduced binge-like high-fat intake. Notably, blocking only ghrelin-triggered receptor activity (using [D-Lys3]-GHRP-6 or JMV2959) did not reduce binge eating, confirming it's the receptor's baseline signaling, not ghrelin binding, that drives this behavior.","whyItMatters":"This study reveals something surprising: the ghrelin receptor can promote binge eating even without ghrelin. The receptor has its own built-in activity that doesn't require the hunger hormone to turn it on. This means binge eating may be driven by brain receptor activity that circulating hormone levels can't predict or fully explain — which could change how we think about treating binge eating disorder and compulsive overeating.","specificNumbers":"4-day binge eating protocol · Constitutive GHSR activity blockers reduced binge HF intake · Ghrelin-evoked blockers had no effect · Plasma ghrelin and LEAP2 levels unchanged during binge protocol","methodology":"Animal study using male mice exposed to a 4-day binge-like eating protocol with time-limited access to high-fat diet. Researchers measured plasma ghrelin and LEAP2 levels during binge eating, then tested the effects of systemically or centrally (brain) administered ghrelin, LEAP2, and various GHSR blockers on high-fat intake. They compared blockers that target ghrelin-stimulated receptor activity versus blockers that target the receptor's constitutive (always-on) activity.","limitations":"This is a mouse study, and binge eating in mice may not fully model human binge eating disorder. Central (brain) administration of drugs is not practical in humans. The 4-day protocol is short-term and may not reflect chronic binge eating patterns. Sample sizes for individual experimental groups are not specified in the abstract. The study does not address what triggers the constitutive GHSR activity or whether it can be modulated long-term."},{"rthcId":"RPEP-04125","title":"A co-delivery platform based on plasmid DNA peptide-surfactant complexes: formation, characterization and release behavior.","authors":"Costa, Diana; Albuquerque, Tânia; Queiroz, João A; Valente, Artur J M","year":2019,"journal":"Colloids and surfaces. B, Biointerfaces, 178, 430-438","doi":"10.1016/j.colsurfb.2019.03.029","pmid":"30908999","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04126","title":"Peptide-Cleavable Self-immolative Maytansinoid Antibody-Drug Conjugates Designed To Provide Improved Bystander Killing.","authors":"Costoplus, Juliet A; Veale, Karen H; Qiu, Qifeng; Ponte, Jose F; Lanieri, Leanne; Setiady, Yulius; Dong, Ling; Skaletskaya, Anna; Bartle, Laura M; Salomon, Paulin; Wu, Rui; Maloney, Erin K; Kovtun, Yelena V; Ab, Olga; Lai, Kate; Chari, Ravi V J; Widdison, Wayne C","year":2019,"journal":"ACS medicinal chemistry letters, 10(10), 1393-1399","doi":"10.1021/acsmedchemlett.9b00310","pmid":"31620224","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tripeptide linkers with all-L or single D-alanyl residues effectively released cytotoxic maytansinoid metabolites inside cells. D-alanyl residues didn't impair activity unless directly attached to the self-immolative group. Extending the maytansinoid side chain increased bystander killing without affecting direct cytotoxicity. The best-performing ADCs showed improved in vivo efficacy compared to previous maytansinoid conjugate designs.","whyItMatters":"Improved bystander killing means ADCs can kill not just the tumor cells they bind to but also nearby cancer cells that may not express the target antigen — addressing a key limitation of conventional ADC therapy in heterogeneous tumors.","specificNumbers":"Tripeptide (trialanyl) linker; D vs L alanyl stereochemistry; variable methylene side chain length; improved in vivo efficacy in mice","methodology":"Conjugates were synthesized with varying peptide linker stereochemistry and maytansinoid side chain lengths. In vitro testing assessed direct cytotoxicity and bystander killing in target-positive and target-negative cells. Best candidates were evaluated in vivo in mouse tumor models and compared to previously described maytansinoid ADC types.","limitations":"Mouse xenograft models may not predict human therapeutic responses. The study focuses on one antibody and one payload class (maytansinoids). Long-term safety and manufacturing feasibility at scale were not addressed. Bystander killing may also affect nearby healthy tissue, potentially increasing toxicity."},{"rthcId":"RPEP-04127","title":"Investigational growth factors utilized in animal models of spinal fusion: Systematic review.","authors":"Cottrill, Ethan; Ahmed, A Karim; Lessing, Noah; Pennington, Zachary; Ishida, Wataru; Perdomo-Pantoja, Alexander; Lo, Sheng-Fu; Howell, Elizabeth; Holmes, Christina; Goodwin, C Rory; Theodore, Nicholas; Sciubba, Daniel M; Witham, Timothy F","year":2019,"journal":"World journal of orthopedics, 10(4), 176-191","doi":"10.5312/wjo.v10.i4.176","pmid":"31041160","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04128","title":"Cathelicidin Contributes to the Restriction of Leishmania in Human Host Macrophages.","authors":"Crauwels, Peter; Bank, Elena; Walber, Bianca; Wenzel, Ulf Alexander; Agerberth, Birgitta; Chanyalew, Menberework; Abebe, Markos; König, Renate; Ritter, Uwe; Reiling, Norbert; van Zandbergen, Ger","year":2019,"journal":"Frontiers in immunology, 10, 2697","doi":"10.3389/fimmu.2019.02697","pmid":"31824492","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04129","title":"Lipidated Stapled Peptides Targeting the Acyl Binding Protein UNC119.","authors":"Cromm, Philipp M; Adihou, Hélène; Kapoor, Shobhna; Vazquez-Chantada, Mercedes; Davey, Paul; Longmire, David; Hennes, Elisabeth; Hofer, Walter; Küchler, Philipp; Chiarparin, Elisabetta; Waldmann, Herbert; Grossmann, Tom N","year":2019,"journal":"Chembiochem : a European journal of chemical biology, 20(24), 2987-2990","doi":"10.1002/cbic.201900615","pmid":"31680402","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04130","title":"Synthesis and Enhanced Cellular Uptake In Vitro of Anti-HER2 Multifunctional Gold Nanoparticles.","authors":"Cruz, Esteban; Kayser, Veysel","year":2019,"journal":"Cancers, 11(6)","doi":"10.3390/cancers11060870","pmid":"31234432","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04131","title":"Cerebrolysin for vascular dementia.","authors":"Cui, Shuhui; Chen, Ning; Yang, Mi; Guo, Jian; Zhou, Muke; Zhu, Cairong; He, Li","year":2019,"journal":"The Cochrane database of systematic reviews, 2019(11)","doi":"10.1002/14651858.CD008900.pub3","pmid":"31710397","tags":["neuroprotection"],"studyType":"systematic-review","evidenceStrength":"weak","keyFinding":"This Cochrane systematic review found that Cerebrolysin — a pig-brain-derived peptide preparation given by intravenous infusion — showed statistically significant improvements in cognition and global function in people with vascular dementia, but the evidence was rated 'very low quality' across the board.\n\nPooling data from three studies (420 participants), Cerebrolysin improved cognitive function scores (SMD 0.36, 95% CI 0.13–0.58). For global function, response rates were 2.69 times higher in the Cerebrolysin group (two studies, 379 participants, RR 2.69, 95% CI 1.82–3.98). No excess adverse effects were found (RR 0.91, 95% CI 0.29–2.85).\n\nHowever, the reviewers concluded these data are 'not definitive.' All included studies had high risk of bias, there was significant heterogeneity between studies, and no new studies had been published since the previous 2013 Cochrane review. The effects may be too small to be clinically meaningful.","whyItMatters":"Vascular dementia is the second most common form of dementia worldwide, yet there are essentially no proven treatments. Cerebrolysin is widely used in parts of Asia, Eastern Europe, and Russia despite weak evidence. This Cochrane review — the gold standard for evidence synthesis — delivers a clear verdict: while there are hints of benefit, the supporting evidence is too weak and too biased to justify confident use. The fact that no new trials have been conducted since 2013 suggests a stalled research agenda for a drug that continues to be prescribed to patients.","specificNumbers":"6 RCTs · 597 total participants · SMD 0.36 for cognition (very low quality) · RR 2.69 for global function response (very low quality) · No excess adverse events · Follow-up 15 days to 3 years · All evidence rated GRADE 'very low'","methodology":"This is a Cochrane systematic review (the highest standard of evidence synthesis). The authors searched 12 databases across multiple languages, checked reference lists, and contacted manufacturers. They included all randomized controlled trials of Cerebrolysin in vascular dementia patients. Two reviewers independently selected trials, assessed methodological quality, and extracted data. Meta-analyses used mean differences or standardized mean differences for continuous outcomes and risk ratios for dichotomous outcomes. Evidence strength was assessed using the GRADE framework.","limitations":"Only 6 small RCTs with 597 total participants were found — far too few for definitive conclusions. All included studies had high risk of bias. Most were conducted in China, Russia, and Romania with industry funding. There was significant heterogeneity in dosing, duration, and follow-up. No studies reported on quality of life or caregiver burden. The GRADE rating of 'very low' means the reviewers have very little confidence that the true effect is close to the estimated effect. No new studies were found since the 2013 review."},{"rthcId":"RPEP-04132","title":"β-Branched Amino Acids Stabilize Specific Conformations of Cyclic Hexapeptides.","authors":"Cummings, Ashleigh E; Miao, Jiayuan; Slough, Diana P; McHugh, Sean M; Kritzer, Joshua A; Lin, Yu-Shan","year":2019,"journal":"Biophysical journal, 116(3), 433-444","doi":"10.1016/j.bpj.2018.12.015","pmid":"30661666","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04133","title":"Hypertension Exacerbates Cerebrovascular Oxidative Stress Induced by Mild Traumatic Brain Injury: Protective Effects of the Mitochondria-Targeted Antioxidative Peptide SS-31.","authors":"Czigler, Andras; Toth, Luca; Szarka, Nikolett; Berta, Gergely; Amrein, Kriszitina; Czeiter, Endre; Lendvai-Emmert, Dominika; Bodo, Kornelia; Tarantini, Stefano; Koller, Akos; Ungvari, Zoltan; Buki, Andras; Toth, Peter","year":2019,"journal":"Journal of neurotrauma, 36(23), 3309-3315","doi":"10.1089/neu.2019.6439","pmid":"31266393","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In spontaneously hypertensive rats (SHRs), mild TBI induced significant long-term increases in both cytoplasmic and mitochondrial superoxide production in middle cerebral arteries at 2 weeks post-injury — an effect not seen in normotensive rats. Expression of the NADPH oxidase subunit Nox4 was also increased. Daily treatment with the mitochondria-targeted peptide SS-31 (5.7 mg/kg/day, i.p.) reversed all these oxidative stress markers to normal levels. NADPH oxidase inhibition (apocynin) also reduced the persistent oxidative stress, confirming the mechanistic pathway.","whyItMatters":"Millions of people experience mild concussions each year, and hypertension is extremely common — especially in older populations prone to falls. This study reveals that this common comorbidity combination may cause persistent brain blood vessel damage that wouldn't occur with either condition alone. The finding that SS-31 (a peptide already in clinical development for other conditions) can reverse this damage identifies a potential therapeutic approach.","specificNumbers":"","methodology":"Researchers induced mild traumatic brain injury in both normotensive Wistar rats and spontaneously hypertensive rats (SHRs). Two weeks after injury, middle cerebral arteries were isolated and assessed for cytoplasmic superoxide (using DHE staining) and mitochondrial superoxide (using MitoSox) by confocal microscopy. Nox4 expression was measured. SS-31 was administered daily at 5.7 mg/kg intraperitoneally. NADPH oxidase inhibition with apocynin was used to confirm the oxidative stress pathway.","limitations":"This is an animal study using an inbred hypertensive rat strain, which may not perfectly model human essential hypertension. The study assessed cerebrovascular oxidative stress markers but did not measure functional outcomes like blood flow or cognition. The 2-week time point is relatively short, and it's unclear if the damage would eventually resolve without treatment or progress further. Only one dose of SS-31 was tested."},{"rthcId":"RPEP-04134","title":"Peptide derivatives as inhibitors of NS2B-NS3 protease from Dengue, West Nile, and Zika flaviviruses.","authors":"da Silva-Júnior, Edeildo Ferreira; de Araújo-Júnior, João Xavier","year":2019,"journal":"Bioorganic & medicinal chemistry, 27(18), 3963-3978","doi":"10.1016/j.bmc.2019.07.038","pmid":"31351847","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identified that the NS2B-NS3 protease active site is shallow and open-pocketed, making it a challenging but critical drug target. Early inhibitors used two basic amino acid residues followed by an electrophilic warhead (such as trifluoromethyl ketones, aldehydes, or boronic acids) that covalently binds to the catalytic serine residue (Ser135). More advanced strategies include incorporating transition metals to create metallopeptide inhibitors and cyclizing linear peptides into macrocyclic structures to improve binding and stability.\n\nThe authors found that different functional group modifications significantly influence both activity and selectivity across the three flavivirus proteases, providing structure-activity relationships that can guide future drug design efforts.","whyItMatters":"With more than 70 identified flaviviruses and no approved antiviral drugs available, millions of people in developing countries rely solely on symptom management when infected. Understanding how peptide-based compounds can block viral replication provides a critical foundation for developing the first targeted treatments for these widespread diseases.","specificNumbers":"70+ flaviviruses identified · 3 major viruses reviewed (DENV, ZIKV, WNV) · 0 approved antiviral drugs · Ser135 catalytic target","methodology":"This was a comprehensive literature review that compiled and analyzed all published peptidomimetic, peptide-derived, and peptide-hybrid compounds tested against NS2B-NS3 proteases from Dengue, Zika, and West Nile viruses. The authors evaluated structure-activity relationships and compared different inhibitor classes.","limitations":"As a review article, this study does not present new experimental data. Most of the inhibitors discussed were tested only in laboratory settings (in vitro), and their effectiveness in living organisms or human clinical trials remains unknown. The shallow, open active site of NS2B-NS3 protease is acknowledged as a major challenge, and many reported inhibitors may not translate into viable drugs."},{"rthcId":"RPEP-04135","title":"Antiinflammatory peptides: current knowledge and promising prospects.","authors":"Dadar, Maryam; Shahali, Youcef; Chakraborty, Sandip; Prasad, Minakshi; Tahoori, Fatemeh; Tiwari, Ruchi; Dhama, Kuldeep","year":2019,"journal":"Inflammation research : official journal of the European Histamine Research Society ... [et al.], 68(2), 125-145","doi":"10.1007/s00011-018-1208-x","pmid":"30560372","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04136","title":"Interactions of thymic stromal lymphopoietin with TLR2 and TLR4 regulate anti-fungal innate immunity in Aspergillus fumigatus-induced corneal infection.","authors":"Dai, Chenyang; Wu, Jiayin; Chen, Chen; Wu, Xinyi","year":2019,"journal":"Experimental eye research, 182, 19-29","doi":"10.1016/j.exer.2019.02.020","pmid":"30853520","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04137","title":"Acute effect of a cod protein hydrolysate on postprandial acylated ghrelin concentration and sensations associated with appetite in healthy subjects: a double-blind crossover trial.","authors":"Dale, Hanna Fjeldheim; Jensen, Caroline; Hausken, Trygve; Lied, Einar; Hatlebakk, Jan Gunnar; Brønstad, Ingeborg; Hoff, Dag Arne Lihaug; Lied, Gülen Arslan","year":2019,"journal":"Food & nutrition research, 63","doi":"10.29219/fnr.v63.3507","pmid":"31692759","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"No statistically significant difference was found between cod protein hydrolysate (CPH) and casein control for postprandial acylated ghrelin concentrations (mean difference: 1.05 pg/mL, 95% CI 0.97–1.13, P = 0.266). The total area under the curve for ghrelin was virtually identical: CPH 17,518 pg/mL × min versus control 17,272 pg/mL × min (P = 0.991).\n\nSubjective appetite measures were also unchanged: no differences between CPH and control for satiety (P = 0.794) or fullness (P = 0.996). The results were consistently null across all time points (0, 20, 40, 80, and 180 minutes postprandially).","whyItMatters":"Bioactive peptides from food protein hydrolysates are widely marketed for metabolic health benefits, but rigorous clinical testing often doesn't support the claims. This well-designed crossover trial shows that at least at a single low dose, cod protein peptides don't affect the hunger hormone ghrelin. This is important for consumers and clinicians evaluating the evidence behind peptide-based nutraceuticals, and it highlights the need for longer-term dosing studies before making health claims.","specificNumbers":"","methodology":"This was a double-blind, crossover exploratory trial with 41 healthy participants (15 males, 26 females, mean age 51 ± 6 years). Each participant completed two study days separated by 4–7 days washout. On each day, they consumed a test drink containing either 20 mg/kg body weight of cod protein hydrolysate or casein (control) immediately before a standardized breakfast. Acylated ghrelin was measured at baseline and five postprandial time points. Appetite sensations were rated on 100 mm Visual Analog Scales.","limitations":"The study tested only a single acute dose, which may be insufficient to affect ghrelin regulation — chronic daily supplementation could produce different results. The dose of 20 mg/kg is relatively low. The casein control is itself a bioactive protein that could mask relative differences. The healthy volunteer population may respond differently than obese or metabolically impaired individuals. The study was self-described as 'explorative,' suggesting it may not have been powered for definitive conclusions."},{"rthcId":"RPEP-04138","title":"Autophagy links antimicrobial activity with antigen presentation in Langerhans cells.","authors":"Dang, Angeline Tilly; Teles, Rosane Mb; Liu, Phillip T; Choi, Aaron; Legaspi, Annalisa; Sarno, Euzenir N; Ochoa, Maria T; Parvatiyar, Kislay; Cheng, Genhong; Gilliet, Michel; Bloom, Barry R; Modlin, Robert L","year":2019,"journal":"JCI insight, 4(8)","doi":"10.1172/jci.insight.126955","pmid":"30996142","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04139","title":"Biochemical and histological characterisation of an experimental rodent model of non-alcoholic steatohepatitis - Effects of a peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist and a glucagon-like peptide-1 analogue.","authors":"Daniels, Samuel J; Leeming, Diana J; Detlefsen, Sönke; Bruun, Maria F; Hjuler, Sara T; Henriksen, Kim; Hein, Peter; Karsdal, Morten A; Brockbank, Sarah; Cruwys, Simon","year":2019,"journal":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 111, 926-933","doi":"10.1016/j.biopha.2018.12.130","pmid":"30841472","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04140","title":"Early Detection of Growth Hormone Secretagogue Receptor Antagonists Exploiting Their Atypical Behavior in Competitive Assays.","authors":"Danila, George Madalin; Puiu, Mihaela; Zamfir, Lucian-Gabriel; Bala, Camelia","year":2019,"journal":"Analytical chemistry, 91(23), 14812-14817","doi":"10.1021/acs.analchem.9b03845","pmid":"31702907","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04141","title":"Δ9-THC and related cannabinoids suppress substance P- induced neurokinin NK1-receptor-mediated vomiting via activation of cannabinoid CB1 receptor.","authors":"Darmani, Nissar A; Belkacemi, Louiza; Zhong, Weixia","year":2019,"journal":"European journal of pharmacology, 865, 172806","doi":"10.1016/j.ejphar.2019.172806","pmid":"31738934","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04142","title":"Synthesis and antiproliferative activities of doxorubicin thiol conjugates and doxorubicin-SS-cyclic peptide.","authors":"Darwish, Shaban; Sadeghiani, Neda; Fong, Shirley; Mozaffari, Saghar; Hamidi, Parinaz; Withana, Thimanthi; Yang, Sun; Tiwari, Rakesh Kumar; Parang, Keykavous","year":2019,"journal":"European journal of medicinal chemistry, 161, 594-606","doi":"10.1016/j.ejmech.2018.10.042","pmid":"30396106","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04143","title":"Evaluation of serum level of substance P and tissue distribution of NK-1 receptor in breast cancer.","authors":"Davoodian, Monireh; Boroumand, Nadia; Mehrabi Bahar, Mostafa; Jafarian, Amir Hosein; Asadi, Mahdi; Hashemy, Seyed Isaac","year":2019,"journal":"Molecular biology reports, 46(1), 1285-1293","doi":"10.1007/s11033-019-04599-9","pmid":"30684188","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04144","title":"Medications development for food-based and drug use disorders.","authors":"de Moura, Fernando B; Kohut, Stephen J; Bergman, Jack","year":2019,"journal":"Advances in pharmacology (San Diego, Calif.), 86, 197-236","doi":"10.1016/bs.apha.2019.04.005","pmid":"31378252","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04145","title":"Cyclotides: From Structure to Function.","authors":"de Veer, Simon J; Kan, Meng-Wei; Craik, David J","year":2019,"journal":"Chemical reviews, 119(24), 12375-12421","doi":"10.1021/acs.chemrev.9b00402","pmid":"31829013","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04146","title":"Cardiovascular Protection with Anti-hyperglycemic Agents.","authors":"Deedwania, Prakash; Acharya, Tushar","year":2019,"journal":"American journal of cardiovascular drugs : drugs, devices, and other interventions, 19(3), 249-257","doi":"10.1007/s40256-019-00325-9","pmid":"30767126","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04147","title":"Regulation of prepubertal dynorphin secretion in the medial basal hypothalamus of the female rat.","authors":"Dees, William L; Hiney, Jill K; Srivastava, Vinod K","year":2019,"journal":"Journal of neuroendocrinology, 31(12), e12810","doi":"10.1111/jne.12810","pmid":"31715027","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04148","title":"Bremelanotide: First Approval.","authors":"Dhillon, Sohita; Keam, Susan J","year":2019,"journal":"Drugs, 79(14), 1599-1606","doi":"10.1007/s40265-019-01187-w","pmid":"31429064","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04149","title":"What's New in the Treatment of Migraine?","authors":"Digre, Kathleen B","year":2019,"journal":"Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society, 39(3), 352-359","doi":"10.1097/WNO.0000000000000837","pmid":"31393282","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04150","title":"Rigorous Computational and Experimental Investigations on MDM2/MDMX-Targeted Linear and Macrocyclic Peptides.","authors":"Diller, David J; Swanson, Jon; Bayden, Alexander S; Brown, Chris J; Thean, Dawn; Lane, David P; Partridge, Anthony W; Sawyer, Tomi K; Audie, Joseph","year":2019,"journal":"Molecules (Basel, Switzerland), 24(24)","doi":"10.3390/molecules24244586","pmid":"31847417","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04151","title":"Differential Susceptibility and Innate Immune Response of Aedes aegypti and Aedes albopictus to the Haitian Strain of the Mayaro Virus.","authors":"Diop, Fodé; Alout, Haoues; Diagne, Cheikh Tidiane; Bengue, Michèle; Baronti, Cécile; Hamel, Rodolphe; Talignani, Loïc; Liegeois, Florian; Pompon, Julien; Morales Vargas, Ronald E; Nougairède, Antoine; Missé, Dorothée","year":2019,"journal":"Viruses, 11(10)","doi":"10.3390/v11100924","pmid":"31601017","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04152","title":"New Therapeutic Approach for Targeting Hippo Signalling Pathway.","authors":"Dominguez-Berrocal, Leticia; Cirri, Erica; Zhang, Xiguang; Andrini, Laura; Marin, Gustavo H; Lebel-Binay, Sophie; Rebollo, Angelita","year":2019,"journal":"Scientific reports, 9(1), 4771","doi":"10.1038/s41598-019-41404-w","pmid":"30886324","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The chimeric tri-functional peptide combined three functional domains into one molecule:\n\n1. A cell-penetrating peptide (CPP) for cellular uptake\n2. A nuclear localization sequence (NLS) for targeting to the nucleus\n3. An interfering peptide that blocks the TEAD-YAP protein-protein interaction\n\nResults demonstrated:\n• Successful cell penetration and nuclear localization confirmed by flow cytometry and fluorescence microscopy\n• Apoptotic (cell death) effects in tumor cell lines\n• Anti-tumoral effects in vivo in breast cancer xenograft mouse models\n• The specific nuclear delivery of the interfering cargo was essential for the anti-cancer effect","whyItMatters":"The TEAD-YAP interaction has been a 'hot target' in cancer research but extremely difficult to drug because it occurs inside the nucleus. Traditional drugs struggle to cross cell membranes, let alone reach the nucleus. This tri-functional peptide solves both delivery challenges in a single molecule while also carrying the therapeutic payload, demonstrating a generalizable design principle for targeting nuclear protein-protein interactions in cancer.","specificNumbers":"","methodology":"The peptide was designed as a chimeric construct with three functional domains. Cell penetration and nuclear localization were validated using flow cytometry and fluorescence microscopy. Anti-cancer activity was tested in vitro on tumor cell lines (measuring apoptosis) and in vivo using xenograft models of breast cancer in mice.","limitations":"Preclinical study with no human data. Xenograft mouse models use human tumors in immunodeficient mice, which don't fully replicate the human tumor microenvironment. Peptide stability and pharmacokinetics in vivo are not discussed in the abstract. The specific tumor cell lines used and quantitative efficacy data are not detailed. Manufacturing complexity of multi-domain chimeric peptides could limit clinical translation. Potential immunogenicity of the CPP domain was not addressed."},{"rthcId":"RPEP-04153","title":"Racial Variations in Appetite-Related Hormones, Appetite, and Laboratory-Based Energy Intake from the E-MECHANIC Randomized Clinical Trial.","authors":"Dorling, James L; Church, Timothy S; Myers, Candice A; Höchsmann, Christoph; White, Ursula A; Hsia, Daniel S; Martin, Corby K; Apolzan, John W","year":2019,"journal":"Nutrients, 11(9)","doi":"10.3390/nu11092018","pmid":"31466276","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"At baseline, African Americans had significantly lower peptide YY (PYY; p<0.05), lower ghrelin (p=0.02), and higher leptin (p<0.05) compared to Whites. Despite these hormonal differences, no racial differences were observed in actual food intake at laboratory-controlled meals.\n\nIn the exercise intervention, leptin increased in African Americans in the 8 KKW exercise group compared to Whites (p=0.01), but no other race-by-group interactions were evident for appetite hormones, appetite ratings, or food intake. The disconnect between hormonal differences and behavioral outcomes suggests that appetite regulation in the context of obesity is more complex than hormone levels alone.","whyItMatters":"Understanding the biological basis of racial obesity disparities is important for developing targeted interventions. This study reveals that while appetite-regulating peptide hormones differ between racial groups, these differences don't directly translate to differences in eating behavior — suggesting that social, environmental, and other biological factors are likely more important drivers of obesity disparities than appetite hormone levels alone.","specificNumbers":"","methodology":"This was a secondary analysis of the E-MECHANIC randomized clinical trial. 164 overweight/obese adults (53 African Americans, 111 Whites) were randomized to a control group or supervised exercise groups at 8 or 20 KKW. Participants consumed standardized lunch and dinner at baseline and follow-up, with appetite ratings and blood hormone levels (PYY, ghrelin, leptin) measured before and after meals. Leptin was measured in fasting samples only.","limitations":"The sample was predominantly from one geographic area (Pennington Biomedical, Louisiana), limiting generalizability. African Americans were underrepresented (53 vs. 111 Whites). Laboratory-based meals may not reflect real-world eating patterns. The study measured a limited set of appetite hormones and did not assess other important mediators like GLP-1 or CCK. Socioeconomic factors, dietary habits, and cultural food preferences were not fully controlled. The exercise intervention was relatively short-term."},{"rthcId":"RPEP-04154","title":"Enhancing the Cell Permeability of Stapled Peptides with a Cyclic Cell-Penetrating Peptide.","authors":"Dougherty, Patrick G; Wen, Jin; Pan, Xiaoyan; Koley, Amritendu; Ren, Jian-Guo; Sahni, Ashweta; Basu, Ruchira; Salim, Heba; Appiah Kubi, George; Qian, Ziqing; Pei, Dehua","year":2019,"journal":"Journal of medicinal chemistry, 62(22), 10098-10107","doi":"10.1021/acs.jmedchem.9b00456","pmid":"31657556","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04155","title":"Understanding Cell Penetration of Cyclic Peptides.","authors":"Dougherty, Patrick G; Sahni, Ashweta; Pei, Dehua","year":2019,"journal":"Chemical reviews, 119(17), 10241-10287","doi":"10.1021/acs.chemrev.9b00008","pmid":"31083977","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04156","title":"The protective effects of lixisenatide against inflammatory response in human rheumatoid arthritis fibroblast-like synoviocytes.","authors":"Du, Xingye; Zhang, Hailin; Zhang, Wenhao; Wang, Qing; Wang, Wei; Ge, Gaoren; Bai, Jiaxiang; Guo, Xiaobin; Zhang, Yunqing; Jiang, Xuefeng; Gu, Jiaye; Xu, Yaozeng; Geng, Dechun","year":2019,"journal":"International immunopharmacology, 75, 105732","doi":"10.1016/j.intimp.2019.105732","pmid":"31336333","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04157","title":"Role of Metformin, Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors, Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists, and Orlistat based Multidrug Therapy in Glycemic Control, Weight Loss, and Euglycemia in Diabesity: A Real-World Experience.","authors":"Dutta, Deep; Jaisani, Ritu; Khandelwal, Deepak; Ghosh, Soumitra; Malhotra, Rajiv; Kalra, Sanjay","year":2019,"journal":"Indian journal of endocrinology and metabolism, 23(4), 460-467","doi":"10.4103/ijem.IJEM_185_19","pmid":"31741907","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04158","title":"Crosstalk between neurokinin receptor signaling and neuroinflammation in neurological disorders.","authors":"Eapen, Prasanth M; Rao, Chamallamudi Mallikarjuna; Nampoothiri, Madhavan","year":2019,"journal":"Reviews in the neurosciences, 30(3), 233-243","doi":"10.1515/revneuro-2018-0021","pmid":"30260793","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04159","title":"Role of CGRP in Migraine.","authors":"Edvinsson, Lars","year":2019,"journal":"Handbook of experimental pharmacology, 255, 121-130","doi":"10.1007/164_2018_201","pmid":"30725283","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04160","title":"Age-related modulation of the isthmic and uterine mucosal innate immune defense system in laying hens.","authors":"Elhamouly, M; Nii, T; Isobe, N; Yoshimura, Y","year":2019,"journal":"Poultry science, 98(7), 3022-3028","doi":"10.3382/ps/pez118","pmid":"30915472","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04161","title":"Changes in gut hormones, glycaemic response and symptoms after oesophagectomy.","authors":"Elliott, J A; Docherty, N G; Murphy, C F; Eckhardt, H-G; Doyle, S L; Guinan, E M; Ravi, N; Reynolds, J V; le Roux, C W","year":2019,"journal":"The British journal of surgery, 106(6), 735-746","doi":"10.1002/bjs.11118","pmid":"30883706","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04162","title":"Cervicovaginal microbiota and local immune response modulate the risk of spontaneous preterm delivery.","authors":"Elovitz, Michal A; Gajer, Pawel; Riis, Valerie; Brown, Amy G; Humphrys, Michael S; Holm, Johanna B; Ravel, Jacques","year":2019,"journal":"Nature communications, 10(1), 1305","doi":"10.1038/s41467-019-09285-9","pmid":"30899005","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04163","title":"Antioxidant properties and potential mechanisms of hydrolyzed proteins and peptides from cereals.","authors":"Esfandi, Ramak; Walters, Mallory E; Tsopmo, Apollinaire","year":2019,"journal":"Heliyon, 5(4), e01538","doi":"10.1016/j.heliyon.2019.e01538","pmid":"31183417","tags":[],"studyType":"review","evidenceStrength":"low-moderate","keyFinding":"Cereals like wheat, rice, corn, barley, oats, and millet contain proteins that, when broken down (hydrolyzed), release peptides with significant antioxidant activity. These food-derived peptides fight oxidative stress through multiple mechanisms: donating hydrogen atoms or electrons to neutralize free radicals, chelating (binding) metals that catalyze oxidation, and regulating enzymes involved in oxidation-reduction processes.\n\nWhile the health benefits of whole grains were previously attributed mainly to fiber (glucans) and polyphenols, this review highlights that bioactive peptides from grain proteins represent an underappreciated category of health-promoting compounds in everyday foods.","whyItMatters":"Oxidative stress is implicated in aging, cancer, cardiovascular disease, and neurodegeneration. Finding antioxidant compounds in staple foods that billions of people already eat could have enormous public health implications. This review shifts attention from the well-known fiber and polyphenol benefits of whole grains to their protein-derived peptides, opening a new dimension of cereal nutrition science.","specificNumbers":"Cereals provide >50% of human energy requirements · 7 major cereals reviewed (wheat, rice, corn, barley, rye, oat, millet) · 3 antioxidant mechanisms: H/electron transfer, metal chelation, enzyme regulation","methodology":"This is a narrative review synthesizing published research on the antioxidant properties of hydrolyzed cereal proteins and peptides. The authors examine evidence from various experimental models (in vitro assays, cell culture, and some in vivo studies) and describe the molecular mechanisms by which these peptides exert antioxidant effects.","limitations":"Most evidence comes from in vitro and cell culture models rather than human clinical trials. The bioavailability of cereal-derived peptides after oral consumption — whether they survive digestion intact and reach tissues in active form — isn't well established. Antioxidant assay results in the lab don't always translate to meaningful health effects in humans. The review doesn't quantify how much of these peptides are actually present in typical diets."},{"rthcId":"RPEP-04164","title":"Raynaud's Phenomenon Associated With Calcitonin Gene-Related Peptide Monoclonal Antibody Antagonists.","authors":"Evans, Randolph W","year":2019,"journal":"Headache, 59(8), 1360-1364","doi":"10.1111/head.13596","pmid":"31310337","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04165","title":"Chimeras of Cell-Penetrating Peptides Demonstrate Synergistic Improvement in Antisense Efficacy.","authors":"Fadzen, Colin M; Holden, Rebecca L; Wolfe, Justin M; Choo, Zi-Ning; Schissel, Carly K; Yao, Monica; Hanson, Gunnar J; Pentelute, Bradley L","year":2019,"journal":"Biochemistry, 58(38), 3980-3989","doi":"10.1021/acs.biochem.9b00413","pmid":"31450889","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04166","title":"Cyclic Peptide Design Guided by Residual Dipolar Couplings, J-Couplings, and Intramolecular Hydrogen Bond Analysis.","authors":"Farley, Kathleen A; Che, Ye; Navarro-Vázquez, Armando; Limberakis, Chris; Anderson, Dennis; Yan, Jiangli; Shapiro, Michael; Shanmugasundaram, Veerabahu; Gil, Roberto R","year":2019,"journal":"The Journal of organic chemistry, 84(8), 4803-4813","doi":"10.1021/acs.joc.8b02811","pmid":"30605335","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04167","title":"Effects of liraglutide, metformin and gliclazide on body composition in patients with both type 2 diabetes and non-alcoholic fatty liver disease: A randomized trial.","authors":"Feng, Wen-Huan; Bi, Yan; Li, Ping; Yin, Ting-Ting; Gao, Cai-Xia; Shen, Shan-Mei; Gao, Li-Jun; Yang, Dong-Hui; Zhu, Da-Long","year":2019,"journal":"Journal of diabetes investigation, 10(2), 399-407","doi":"10.1111/jdi.12888","pmid":"29957886","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04168","title":"Structure and dynamics of G protein-coupled receptor-bound ghrelin reveal the critical role of the octanoyl chain.","authors":"Ferré, Guillaume; Louet, Maxime; Saurel, Oliver; Delort, Bartholomé; Czaplicki, Georges; M'Kadmi, Céline; Damian, Marjorie; Renault, Pedro; Cantel, Sonia; Gavara, Laurent; Demange, Pascal; Marie, Jacky; Fehrentz, Jean-Alain; Floquet, Nicolas; Milon, Alain; Banères, Jean-Louis","year":2019,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 116(35), 17525-17530","doi":"10.1073/pnas.1905105116","pmid":"31416915","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04169","title":"Metallacarboranes as a tool for enhancing the activity of therapeutic peptides.","authors":"Fink, Krzysztof; Boratyński, Janusz; Paprocka, Maria; Goszczyński, Tomasz M","year":2019,"journal":"Annals of the New York Academy of Sciences, 1457(1), 128-141","doi":"10.1111/nyas.14201","pmid":"31407357","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04170","title":"High-Frequency Activation of Nucleus Accumbens D1-MSNs Drives Excitatory Potentiation on D2-MSNs.","authors":"Francis, T Chase; Yano, Hideaki; Demarest, Tyler G; Shen, Hui; Bonci, Antonello","year":2019,"journal":"Neuron, 103(3), 432-444.e3","doi":"10.1016/j.neuron.2019.05.031","pmid":"31221559","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04171","title":"No Association of Variants of the NPY-System With Obsessive-Compulsive Disorder in Children and Adolescents.","authors":"Franke, Maximilian; Conzelmann, Annette; Grünblatt, Edna; Werling, Anna M; Spieles, Helen; Wewetzer, Christoph; Warnke, Andreas; Romanos, Marcel; Walitza, Susanne; Renner, Tobias J","year":2019,"journal":"Frontiers in molecular neuroscience, 12, 112","doi":"10.3389/fnmol.2019.00112","pmid":"31133798","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04172","title":"Vasoactive intestinal peptide ameliorates renal injury in a pristane-induced lupus mouse model by modulating Th17/Treg balance.","authors":"Fu, Dongdong; Senouthai, Soulixay; Wang, Junjie; You, Yanwu","year":2019,"journal":"BMC nephrology, 20(1), 350","doi":"10.1186/s12882-019-1548-y","pmid":"31488076","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04173","title":"Ethosomal Gel for Improving Transdermal Delivery of Thymosin β-4.","authors":"Fu, Xianglei; Shi, Yanbin; Wang, Hui; Zhao, Xiaogang; Sun, Qifeng; Huang, Yi; Qi, Tongtong; Lin, Guimei","year":2019,"journal":"International journal of nanomedicine, 14, 9275-9284","doi":"10.2147/IJN.S228863","pmid":"31819429","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04174","title":"A novel technique to diagnose non-melanoma skin cancer by thermal conductivity measurements: Correlations with cancer stromal factors.","authors":"Fujimura, Taku; Okabe, Takahiro; Tanita, Kayo; Sato, Yota; Lyu, Chunbing; Kambayashi, Yumi; Maruyama, Shigenao; Aiba, Setsuya","year":2019,"journal":"Experimental dermatology, 28(9), 1029-1035","doi":"10.1111/exd.13997","pmid":"31264287","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04175","title":"Cystathionine-Gamma-Lyase-Derived Hydrogen Sulfide-Regulated Substance P Modulates Liver Sieve Fenestrations in Caecal Ligation and Puncture-Induced Sepsis.","authors":"Gaddam, Ravinder R; Chambers, Stephen; Fraser, Robin; Cogger, Victoria C; Le Couteur, David G; Ishii, Isao; Bhatia, Madhav","year":2019,"journal":"International journal of molecular sciences, 20(13)","doi":"10.3390/ijms20133191","pmid":"31261857","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04176","title":"Glycine-modified growth hormone secretagogues identified in seized doping material.","authors":"Gajda, Paulina Marta; Holm, Niels Bjerre; Hoej, Lars Jakobsen; Rasmussen, Brian Schou; Dalsgaard, Petur Weihe; Reitzel, Lotte Ask; Linnet, Kristian","year":2019,"journal":"Drug testing and analysis, 11(2), 350-354","doi":"10.1002/dta.2489","pmid":"30136411","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04177","title":"Novel plasma peptide markers involved in the pathology of CKD identified using mass spectrometric approach.","authors":"Gajjala, Prathibha R; Bruck, Heike; Noels, Heidi; Heinze, Georg; Ceccarelli, Francesco; Kribben, Andreas; Saez-Rodriguez, Julio; Marx, Nikolaus; Zidek, Walter; Jankowski, Joachim; Jankowski, Vera","year":2019,"journal":"Journal of molecular medicine (Berlin, Germany), 97(10), 1451-1463","doi":"10.1007/s00109-019-01823-8","pmid":"31385015","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Using untargeted plasma peptidomics, researchers identified 14 peptide substances with concentrations that varied according to kidney function. Seven were most likely to be elevated in CKD patients. The peptidomic score model achieved an area under the curve of 0.87 (95% CI: 0.815-0.919; p < 0.0001), indicating strong diagnostic accuracy.\n\nThe score was significantly higher in CKD than non-CKD patients (2.539 ± 0.264 vs -0.938 ± 0.169). Remarkably, the model also predicted CKD stages with a Spearman correlation of 0.83 and concordance index of 0.899 (95% CI: 0.863-0.927). In univariate analysis, the peptidomic score was most strongly associated with C-reactive protein, sodium, and uric acid — substances not previously prioritized in CKD peptide research.","whyItMatters":"Chronic kidney disease affects over 800 million people worldwide, and early detection of who will progress to kidney failure is one of the biggest unmet needs in nephrology. Current tests like creatinine and GFR are lagging indicators — by the time they change significantly, damage has already occurred. A blood peptide panel that can predict progression early could transform how kidney disease is monitored, enabling earlier intervention and potentially preventing dialysis for millions.","specificNumbers":"","methodology":"Researchers performed untargeted plasma peptidomics on 172 subjects (66 non-CKD, 106 CKD at various stages) using liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS). They applied LASSO logistic regression to select differentially expressed peptides and created a peptidomic scoring model. Selected peptides were identified and sequenced using MALDI-MS/MS. Univariate and multivariate analyses were performed to assess associations between the peptidomic score and clinical variables related to disease progression.","limitations":"This was a cross-sectional study, meaning it measured peptide levels at one point in time rather than tracking patients over years to see who actually progressed. The 14 identified peptides need validation in independent, larger cohorts. The study did not include a longitudinal component to confirm predictive power for disease progression. Some of the identified peptide markers were novel and their biological roles in CKD are not yet understood."},{"rthcId":"RPEP-04178","title":"Consideration of Binding Kinetics in the Design of Stapled Peptide Mimics of the Disordered Proteins Eukaryotic Translation Initiation Factor 4E-Binding Protein 1 and Eukaryotic Translation Initiation Factor 4G.","authors":"Gallagher, Erin E; Song, James M; Menon, Arya; Mishra, Lauren D; Chmiel, Alyah F; Garner, Amanda L","year":2019,"journal":"Journal of medicinal chemistry, 62(10), 4967-4978","doi":"10.1021/acs.jmedchem.9b00068","pmid":"31033289","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04179","title":"Pulp response of rats submitted to bleaching and the use of different anti-inflammatory drugs.","authors":"Gallinari, Marjorie de Oliveira; Cintra, Luciano Tavares Ângelo; Benetti, Francine; Rahal, Vanessa; Ervolino, Edilson; Briso, André Luiz Fraga","year":2019,"journal":"PloS one, 14(1), e0210338","doi":"10.1371/journal.pone.0210338","pmid":"30620760","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04180","title":"Peptide Super-Agonist Enhances T-Cell Responses to Melanoma.","authors":"Galloway, Sarah A E; Dolton, Garry; Attaf, Meriem; Wall, Aaron; Fuller, Anna; Rius, Cristina; Bianchi, Valentina; Theaker, Sarah; Lloyd, Angharad; Caillaud, Marine E; Svane, Inge Marie; Donia, Marco; Cole, David K; Szomolay, Barbara; Rizkallah, Pierre; Sewell, Andrew K","year":2019,"journal":"Frontiers in immunology, 10, 319","doi":"10.3389/fimmu.2019.00319","pmid":"30930889","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04181","title":"Effects of Amylin Against Amyloid-β-Induced Tauopathy and Synapse Loss in Primary Neurons.","authors":"Gan, Qini; Yao, Hongbo; Na, Hana; Ballance, Heather; Tao, Qiushan; Leung, Lorene; Tian, Hua; Zhu, Haihao; Wolozin, Benjamin; Qiu, Wei Qiao","year":2019,"journal":"Journal of Alzheimer's disease : JAD, 70(4), 1025-1040","doi":"10.3233/JAD-190161","pmid":"31306122","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04182","title":"Visualizing the cellular route of entry of a cystine-knot peptide with Xfect transfection reagent by electron microscopy.","authors":"Gao, Xinxin; De Mazière, Ann; Iaea, David B; Arthur, Christopher P; Klumperman, Judith; Ciferri, Claudio; Hannoush, Rami N","year":2019,"journal":"Scientific reports, 9(1), 6907","doi":"10.1038/s41598-019-43285-5","pmid":"31061420","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04183","title":"Development of a multiplex assay based on chimeric citrullinated peptides as proof of concept for diagnosis of rheumatoid arthritis.","authors":"García-Moreno, Cristina; Gómara, María José; Bleda, María José; Sanmartí, Raimon; Haro, Isabel","year":2019,"journal":"PloS one, 14(5), e0215927","doi":"10.1371/journal.pone.0215927","pmid":"31048864","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04184","title":"Tumor-targeted silencing of the peptide transporter TAP induces potent antitumor immunity.","authors":"Garrido, Greta; Schrand, Brett; Rabasa, Ailem; Levay, Agata; D'Eramo, Francesca; Berezhnoy, Alexey; Modi, Shrey; Gefen, Tal; Marijt, Koen; Doorduijn, Elien; Dudeja, Vikas; van Hall, Thorbald; Gilboa, Eli","year":2019,"journal":"Nature communications, 10(1), 3773","doi":"10.1038/s41467-019-11728-2","pmid":"31434881","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Silencing the peptide transporter TAP in tumor cells forced them to present a new set of peptide antigens that the immune system could recognize and attack. Tumor-targeted delivery of TAP siRNA via a nucleolin aptamer inhibited tumor growth across multiple tumor models without measurable toxicity. The approach was comparably effective to vaccination against mutation-generated neoantigens, potentiated the effects of PD-1 antibody and Flt3 ligand, and induced TAP-independent peptide presentation in human tumor cells.","whyItMatters":"Most cancer immunotherapy works best when tumors have many neoantigens (mutations the immune system can target). But many cancers have few neoantigens, making them resistant to checkpoint inhibitors. This study introduces a creative workaround: instead of finding existing neoantigens, force tumors to create new ones by blocking their peptide processing machinery. By shutting down TAP, the tumor cell surface displays an entirely different set of peptides that the immune system treats as foreign. This could make immunotherapy-resistant 'cold' tumors into targetable 'hot' tumors.","specificNumbers":"Multiple tumor models · Nucleolin aptamer-TAP siRNA conjugate · No measurable toxicity · Comparable to neoantigen vaccination · Potentiated PD-1 + Flt3L · Human tumor cell validation · Published in Nature Communications","methodology":"Chemically synthesized nucleolin aptamer (targeting tumors) was conjugated to TAP-targeting siRNA. The conjugate was administered systemically in mice bearing various tumor types. Tumor growth, immune responses, and toxicity were assessed. Combination experiments tested TAP silencing with PD-1 antibody and Flt3 ligand. Human tumor cells were tested for TAP-independent peptide presentation in vitro.","limitations":"Preclinical mouse study — human tumors in vivo may respond differently. TAP silencing is transient (siRNA effect), so repeated dosing would be needed. The nucleolin aptamer targets broadly rather than tumor-specifically, though toxicity was minimal. Whether the TAP-independent peptide repertoire is sufficiently immunogenic in humans with their diverse HLA types needs clinical testing."},{"rthcId":"RPEP-04185","title":"Intracellular delivery of therapeutic antibodies into specific cells using antibody-peptide fusions.","authors":"Gaston, Julie; Maestrali, Nicolas; Lalle, Guilhem; Gagnaire, Marie; Masiero, Alessandro; Dumas, Bruno; Dabdoubi, Tarik; Radošević, Katarina; Berne, Pierre-François","year":2019,"journal":"Scientific reports, 9(1), 18688","doi":"10.1038/s41598-019-55091-0","pmid":"31822703","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04186","title":"Neuropeptides: important regulators of joint homeostasis.","authors":"Gatenholm, Birgitta; Brittberg, Mats","year":2019,"journal":"Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA, 27(3), 942-949","doi":"10.1007/s00167-018-5074-4","pmid":"30039292","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies substance P, calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), and neuropeptide Y as the four major neuropeptides involved in joint pain — both in generating pain signals after trauma and in modulating pain reduction. Critically, the neuropeptide changes observed in subchondral bone and synovial tissue are mirrored in the central nervous system, indicating a bidirectional communication system.\n\nThese neuropeptides interact with each other and with cytokines in a complex cascade that determines how pain signals are generated, transmitted, and perceived. The joint functions as an integrated organ where local neuropeptide signaling and CNS processing work together to respond to mechanical load, injury, and inflammation.","whyItMatters":"Osteoarthritis affects hundreds of millions of people worldwide and current pain treatments are limited. Understanding that neuropeptides are not just pain messengers but active regulators of joint health and disease opens entirely new therapeutic avenues. Rather than simply blocking pain signals, future treatments could target the specific neuropeptide pathways driving both pain and joint degeneration.","specificNumbers":"","methodology":"Systematic literature review covering papers published between January 1990 and September 2017, searched across Web of Science Core Collection, MEDLINE, and Scopus databases. The review synthesizes findings on neuropeptide roles in joint pain transmission and osteoarthritis progression.","limitations":"As a narrative literature review, this paper synthesizes existing evidence without performing a meta-analysis or reporting pooled quantitative results. The proposed slow-release antibody cocktail treatment remains theoretical with no clinical data. The literature search ended in 2017, so more recent findings may not be included. The review focuses on osteoarthritis and may not fully address other joint conditions."},{"rthcId":"RPEP-04187","title":"Cationic antimicrobial peptides: alternatives and/or adjuvants to antibiotics active against methicillin-resistant Staphylococcus aureus and multidrug-resistant Pseudomonas aeruginosa.","authors":"Geitani, Regina; Ayoub Moubareck, Carole; Touqui, Lhousseine; Karam Sarkis, Dolla","year":2019,"journal":"BMC microbiology, 19(1), 54","doi":"10.1186/s12866-019-1416-8","pmid":"30849936","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04188","title":"The peptide hormone glucagon forms amyloid fibrils with two coexisting β-strand conformations.","authors":"Gelenter, Martin D; Smith, Katelyn J; Liao, Shu-Yu; Mandala, Venkata S; Dregni, Aurelio J; Lamm, Matthew S; Tian, Yu; Xu, Wei; Pochan, Darrin J; Tucker, Thomas J; Su, Yongchao; Hong, Mei","year":2019,"journal":"Nature structural & molecular biology, 26(7), 592-598","doi":"10.1038/s41594-019-0238-6","pmid":"31235909","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04189","title":"Molecular simulation of peptides coming of age: Accurate prediction of folding, dynamics and structures.","authors":"Georgoulia, Panagiota S; Glykos, Nicholas M","year":2019,"journal":"Archives of biochemistry and biophysics, 664, 76-88","doi":"10.1016/j.abb.2019.01.033","pmid":"30711540","tags":["peptide-engineering","computational"],"studyType":"review","evidenceStrength":"n/a-review","keyFinding":"Molecular dynamics (MD) simulations have made significant progress over the past two decades in accurately predicting how peptides fold, move, and take shape. Peptides have become a favored test system for computational methods because their smaller size makes them tractable for simulation while still being relevant to protein structure prediction and drug design.\n\nHowever, the accuracy of these simulations depends entirely on the mathematical models (force fields) used to describe molecular interactions. A major remaining challenge is simulating intrinsically disordered peptides — those that don't fold into fixed shapes — where current force fields still struggle to accurately capture their flexible behavior.","whyItMatters":"Before testing a peptide drug in the lab, scientists increasingly use computer simulations to predict whether it will fold into the right shape to work. This review documents how far these computational methods have come and where they still fall short. Getting peptide simulation right is crucial for accelerating drug discovery — accurate predictions mean fewer expensive lab experiments and faster paths to new medicines.","specificNumbers":"20+ years of development · Successful protein folding predictions achieved · Disordered peptides remain a challenge · Force field accuracy is the limiting factor","methodology":"Review article surveying two decades of molecular dynamics simulation research applied to peptide folding, dynamics, and structure prediction, with focus on force field development and validation.","limitations":"As a review, no new simulation data is presented. The field moves quickly and specific force field comparisons may be outdated. The review acknowledges that disordered peptide simulation remains unsolved, but doesn't fully quantify the gap between simulation and experiment."},{"rthcId":"RPEP-04190","title":"Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial.","authors":"Gerstein, Hertzel C; Colhoun, Helen M; Dagenais, Gilles R; Diaz, Rafael; Lakshmanan, Mark; Pais, Prem; Probstfield, Jeffrey; Riesmeyer, Jeffrey S; Riddle, Matthew C; Rydén, Lars; Xavier, Denis; Atisso, Charles Messan; Dyal, Leanne; Hall, Stephanie; Rao-Melacini, Purnima; Wong, Gloria; Avezum, Alvaro; Basile, Jan; Chung, Namsik; Conget, Ignacio; Cushman, William C; Franek, Edward; Hancu, Nicolae; Hanefeld, Markolf; Holt, Shaun; Jansky, Petr; Keltai, Matyas; Lanas, Fernando; Leiter, Lawrence A; Lopez-Jaramillo, Patricio; Cardona Munoz, Ernesto German; Pirags, Valdis; Pogosova, Nana; Raubenheimer, Peter J; Shaw, Jonathan E; Sheu, Wayne H-H; Temelkova-Kurktschiev, Theodora","year":2019,"journal":"Lancet (London, England), 394(10193), 121-130","doi":"10.1016/S0140-6736(19)31149-3","pmid":"31189511","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04191","title":"New Avenues in the Regulation of Gallbladder Motility-Implications for the Use of Glucagon-Like Peptide-Derived Drugs.","authors":"Gether, Ida M; Nexøe-Larsen, Christina; Knop, Filip K","year":2019,"journal":"The Journal of clinical endocrinology and metabolism, 104(7), 2463-2472","doi":"10.1210/jc.2018-01008","pmid":"30137354","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04192","title":"Stability Evaluation and Stabilization of a Gastrin-Releasing Peptide Receptor (GRPR) Targeting Imaging Pharmaceutical.","authors":"Ghosh, Arijit; Woolum, Karen; Kothandaraman, Shankaran; Tweedle, Michael F; Kumar, Krishan","year":2019,"journal":"Molecules (Basel, Switzerland), 24(16)","doi":"10.3390/molecules24162878","pmid":"31398865","tags":["peptide-imaging"],"studyType":"in-vitro-study","evidenceStrength":"preliminary","keyFinding":"The GRPR-targeting antagonist peptide RM1, when labeled with lutetium-177, proved more stable than the agonist peptide AMBA in mouse, canine, and human sera. Degradation followed the order: mouse sera (fastest) > canine > human sera (slowest), meaning the peptide lasts longest in human blood.\n\nHigher radioconcentrations caused faster degradation of 177Lu-labeled RM1 during storage at 2–8°C. Adding stabilizers significantly improved shelf stability, with gentisic acid outperforming ascorbic acid. These findings support RM1 antagonist as the more promising candidate for both PET imaging and potential therapy of prostate cancer.","whyItMatters":"For peptide-based cancer imaging to work in the clinic, the radiolabeled peptide must remain stable long enough to reach the tumor and produce a clear image. This study addressed a practical barrier — figuring out how to keep these peptides from degrading — and identified both a better peptide candidate (antagonist over agonist) and effective stabilizers that could extend shelf life.","specificNumbers":"2 peptides compared (AMBA agonist vs RM1 antagonist) · 177Lu radiolabel · stability tested in acetate buffer + mouse, canine, and human sera · gentisic acid > ascorbic acid as stabilizer","methodology":"Researchers compared the stability of two lutetium-177-labeled peptides — the AMBA agonist and RM1 antagonist — that target the gastrin-releasing peptide receptor found on prostate cancer cells. They tested stability in acetate buffer and in sera from mice, dogs, and humans at different radioconcentrations and storage temperatures. They also tested whether adding ascorbic acid or gentisic acid could prevent degradation.","limitations":"This is an in-vitro stability study — it tests how well the peptides hold up in buffer and blood serum, not how well they perform in living patients. No imaging or therapeutic outcomes were measured. The study focused on lutetium-177 labeling specifically, so results may differ with other radioisotopes."},{"rthcId":"RPEP-04193","title":"Injectable Alginate-Peptide Composite Hydrogel as a Scaffold for Bone Tissue Regeneration.","authors":"Ghosh, Moumita; Halperin-Sternfeld, Michal; Grinberg, Itzhak; Adler-Abramovich, Lihi","year":2019,"journal":"Nanomaterials (Basel, Switzerland), 9(4)","doi":"10.3390/nano9040497","pmid":"30939729","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04194","title":"In vitro-digested milk proteins: Evaluation of angiotensin-1-converting enzyme inhibitory and antioxidant activities, peptidomic profile, and mucin gene expression in HT29-MTX cells.","authors":"Giromini, Carlotta; Lovegrove, Julie A; Givens, David I; Rebucci, Raffaella; Pinotti, Luciano; Maffioli, Elisa; Tedeschi, Gabriella; Sundaram, Tamil S; Baldi, Antonella","year":2019,"journal":"Journal of dairy science, 102(12), 10760-10771","doi":"10.3168/jds.2019-16833","pmid":"31521344","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04195","title":"GLP-1 receptor agonists for prevention of cardiorenal outcomes in type 2 diabetes: An updated meta-analysis including the REWIND and PIONEER 6 trials.","authors":"Giugliano, Dario; Maiorino, Maria Ida; Bellastella, Giuseppe; Longo, Miriam; Chiodini, Paolo; Esposito, Katherine","year":2019,"journal":"Diabetes, obesity & metabolism, 21(11), 2576-2580","doi":"10.1111/dom.13847","pmid":"31373167","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04196","title":"Heart failure and type 2 diabetes: From cardiovascular outcome trials, with hope.","authors":"Giugliano, Dario; Meier, Juris J; Esposito, Katherine","year":2019,"journal":"Diabetes, obesity & metabolism, 21(5), 1081-1087","doi":"10.1111/dom.13629","pmid":"30609236","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04197","title":"Incretin Mimetics as Rational Candidates for the Treatment of Traumatic Brain Injury.","authors":"Glotfelty, Elliot J; Delgado, Thomas; Tovar-Y-Romo, Luis B; Luo, Yu; Hoffer, Barry; Olson, Lars; Karlsson, Tobias; Mattson, Mark P; Harvey, Brandon; Tweedie, David; Li, Yazhou; Greig, Nigel H","year":2019,"journal":"ACS pharmacology & translational science, 2(2), 66-91","doi":"10.1021/acsptsci.9b00003","pmid":"31396586","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04198","title":"Primary headache disorders: Five new things.","authors":"Goadsby, Peter J","year":2019,"journal":"Neurology. Clinical practice, 9(3), 233-240","doi":"10.1212/CPJ.0000000000000654","pmid":"31341711","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review covers five advances in primary headache disorders:\n\n1. CGRP receptor antagonists (gepants): Rimegepant and ubrogepant completed Phase 3 trials for acute migraine, offering effective non-vasoconstrictor alternatives to triptans\n2. CGRP monoclonal antibodies for prevention: Three licensed (erenumab, fremanezumab, galcanezumab) with eptinezumab to follow — the first migraine-specific preventive treatments, effective and well tolerated\n3. Neuromodulation: Transcranial magnetic stimulation, noninvasive vagus nerve stimulation (nVNS), and external trigeminal nerve stimulation licensed for migraine\n4. Cluster headache advances: nVNS effective for acute and preventive treatment; galcanezumab effective for episodic cluster headache prevention in a controlled trial\n5. Premonitory phase understanding: Recognizing prodromal symptoms may help explain apparent migraine triggers and improve self-management","whyItMatters":"Migraine is the most common reason to visit a neurologist, affecting over 1 billion people globally. Before CGRP-targeting therapies, migraine treatments were all repurposed from other conditions (blood pressure drugs, antidepressants, seizure medications). The CGRP revolution represents the first time treatments were designed specifically for migraine based on understanding the underlying peptide biology.","specificNumbers":"","methodology":"This is a clinical review by Peter Goadsby (a leading headache researcher) summarizing five key developments in primary headache disorders, focusing on clinical trial results and newly licensed therapies.","limitations":"Written in 2019, this review captured the field at a transitional moment. Long-term safety data for CGRP-targeting therapies was still limited. Cost and access issues were not addressed. The review focuses mainly on episodic migraine and cluster headache, with less coverage of chronic migraine subtypes."},{"rthcId":"RPEP-04199","title":"Targeting Peripheral CB1 Receptors Reduces Ethanol Intake via a Gut-Brain Axis.","authors":"Godlewski, Grzegorz; Cinar, Resat; Coffey, Nathan J; Liu, Jie; Jourdan, Tony; Mukhopadhyay, Bani; Chedester, Lee; Liu, Ziyi; Osei-Hyiaman, Douglas; Iyer, Malliga R; Park, Joshua K; Smith, Roy G; Iwakura, Hiroshi; Kunos, George","year":2019,"journal":"Cell metabolism, 29(6), 1320-1333.e8","doi":"10.1016/j.cmet.2019.04.012","pmid":"31105045","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04200","title":"Conceptualization of a Parasympathetic Endocrine System.","authors":"Gorky, Jonathan; Schwaber, James","year":2019,"journal":"Frontiers in neuroscience, 13, 1008","doi":"10.3389/fnins.2019.01008","pmid":"31607849","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The authors propose that circulating gut-derived peptides — including somatostatin, cholecystokinin, glucagon-like peptide 1, and vasoactive intestinal peptide — form a coordinated parasympathetic endocrine system (PES) with the dorsal motor nucleus of the vagus (DMV) as its integrative controller.\n\nBeyond their well-known satiety and digestive effects, these peptides broadly increase parasympathetic signaling and directly antagonize sympathetic signaling in mammals. The authors present anatomical evidence (vagal projections to gut secretory cells), physiological control mechanisms (peptide-mediated parasympathetic modulation), and examples of direct PES antagonism of sympathetic activity to support this conceptual framework.","whyItMatters":"Metabolic syndrome — the cluster of obesity, diabetes, high blood pressure, and cardiovascular disease — is one of the biggest health challenges worldwide. If gut peptides truly function as a coordinated system opposing stress-driven disease, this reframes metabolic syndrome as partly a failure of parasympathetic endocrine signaling. This could explain why GLP-1 drugs have benefits far beyond blood sugar control and point toward new multi-peptide therapeutic strategies.","specificNumbers":"","methodology":"This is a conceptual/hypothesis paper that synthesizes existing anatomical, physiological, and pharmacological evidence to propose a new framework. The authors reviewed evidence on gut-derived peptide actions, vagal nerve anatomy, and autonomic nervous system signaling to build the case for a coordinated parasympathetic endocrine system.","limitations":"This is a hypothesis/conceptual paper, not a study with experimental data. While the authors present supporting evidence from existing literature, the PES concept has not been experimentally validated as a coordinated system. The review focuses on gut-derived peptides and acknowledges that other sites (lung, liver) may also contribute. The precise mechanisms of DMV coordination of peptide release need further investigation."},{"rthcId":"RPEP-04201","title":"Advances in the physiology of gastric emptying.","authors":"Goyal, Raj K; Guo, Yanmei; Mashimo, Hiroshi","year":2019,"journal":"Neurogastroenterology and motility, 31(4), e13546","doi":"10.1111/nmo.13546","pmid":"30740834","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04202","title":"Synthesis of Anthracene Conjugates of Truncated Antifreeze Protein Sequences: Effect of the End Group and Photocontrolled Dimerization on Ice Recrystallization Inhibition Activity.","authors":"Graham, Ben; Fayter, Alice E R; Gibson, Matthew I","year":2019,"journal":"Biomacromolecules, 20(12), 4611-4621","doi":"10.1021/acs.biomac.9b01538","pmid":"31714763","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04203","title":"Anti-Müllerian Hormone and Its Predictive Utility in Assisted Reproductive Technologies Outcomes.","authors":"Granger, Emily; Tal, Reshef","year":2019,"journal":"Clinical obstetrics and gynecology, 62(2), 238-256","doi":"10.1097/GRF.0000000000000436","pmid":"30994481","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04204","title":"Ghrelin regulation of glucose metabolism.","authors":"Gray, Sarah M; Page, Laura C; Tong, Jenny","year":2019,"journal":"Journal of neuroendocrinology, 31(7), e12705","doi":"10.1111/jne.12705","pmid":"30849212","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04205","title":"A Mast-Cell-Specific Receptor Mediates Neurogenic Inflammation and Pain.","authors":"Green, Dustin P; Limjunyawong, Nathachit; Gour, Naina; Pundir, Priyanka; Dong, Xinzhong","year":2019,"journal":"Neuron, 101(3), 412-420.e3","doi":"10.1016/j.neuron.2019.01.012","pmid":"30686732","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04206","title":"Glucagon-Like Peptide-1: A Focus on Neurodegenerative Diseases.","authors":"Grieco, Maddalena; Giorgi, Alessandra; Gentile, Maria Cristina; d'Erme, Maria; Morano, Susanna; Maras, Bruno; Filardi, Tiziana","year":2019,"journal":"Frontiers in neuroscience, 13, 1112","doi":"10.3389/fnins.2019.01112","pmid":"31680842","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 receptor agonists demonstrated neuroprotective effects across multiple animal models of neurological disease. In Parkinson's disease models, they protected dopaminergic neurons and preserved motor function. In Alzheimer's disease models, they improved nearly all neuropathological features and cognitive functions, including reducing amyloid beta peptide aggregation. In stroke models, they reduced cerebral infarct area and improved neurological deficits.\n\nThe mechanisms appear to involve inhibition of oxidative stress, inflammation, and apoptosis (programmed cell death), as well as improvement of synaptic plasticity — the brain's ability to form and strengthen connections. These benefits were observed even in animals without diabetes, suggesting the neuroprotective effects are independent of blood sugar control.","whyItMatters":"With diabetes affecting over 400 million people worldwide and serving as a major risk factor for dementia, finding treatments that address both conditions simultaneously would be transformative. GLP-1 receptor agonists like semaglutide and liraglutide are already FDA-approved and widely prescribed, meaning if their neuroprotective benefits are confirmed in human trials, millions of patients could benefit from drugs that are already available — a much faster path than developing entirely new brain therapies.","specificNumbers":"","methodology":"This is a narrative review paper that synthesized findings from multiple published studies on GLP-1 and its receptor agonists in the context of neurodegenerative diseases. The authors reviewed preclinical animal studies, mechanistic research, and the limited clinical data available at the time of publication.","limitations":"As a review paper, this does not present new experimental data. The neuroprotective evidence discussed comes almost entirely from animal models, which do not always translate to human outcomes. The review is narrative rather than systematic, meaning it may not capture all relevant studies or assess them for bias. At the time of publication, clinical trial data in humans for neurological indications was very limited."},{"rthcId":"RPEP-04207","title":"Prognostic Implications of Changes in Amino-Terminal Pro-B-Type Natriuretic Peptide in Acute Decompensated Heart Failure: Insights From ASCEND-HF.","authors":"Grodin, Justin L; Liebo, Max J; Butler, Javed; Metra, Marco; Felker, G Michael; Hernandez, Adrian F; Voors, Adriaan A; McMurray, John J; Armstrong, Paul W; O'Connor, Christopher; Starling, Randall C; Troughton, Richard W; Tang, W H Wilson","year":2019,"journal":"Journal of cardiac failure, 25(9), 703-711","doi":"10.1016/j.cardfail.2019.04.002","pmid":"30953792","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04208","title":"Induction of tumor-specific CTL responses using the C-terminal fragment of Viral protein R as cell penetrating peptide.","authors":"Gross, D A; Leborgne, C; Chappert, P; Masurier, C; Leboeuf, M; Monteilhet, V; Boutin, S; Lemonnier, F A; Davoust, J; Kichler, A","year":2019,"journal":"Scientific reports, 9(1), 3937","doi":"10.1038/s41598-019-40594-7","pmid":"30850685","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04209","title":"Isoleucine Plays an Important Role for Maintaining Immune Function.","authors":"Gu, Changsong; Mao, Xiangbing; Chen, Daiwen; Yu, Bing; Yang, Qing","year":2019,"journal":"Current protein & peptide science, 20(7), 644-651","doi":"10.2174/1389203720666190305163135","pmid":"30843485","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04210","title":"Macrocyclic Control in Helix Mimetics.","authors":"Guarracino, Danielle A; Riordan, Jacob A; Barreto, Gianna M; Oldfield, Alexis L; Kouba, Christopher M; Agrinsoni, Desiree","year":2019,"journal":"Chemical reviews, 119(17), 9915-9949","doi":"10.1021/acs.chemrev.8b00623","pmid":"31045350","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04211","title":"β1-adrenergic receptors mediate plasma acyl-ghrelin elevation and depressive-like behavior induced by chronic psychosocial stress.","authors":"Gupta, Deepali; Chuang, Jen-Chieh; Mani, Bharath K; Shankar, Kripa; Rodriguez, Juan A; Osborne-Lawrence, Sherri; Metzger, Nathan P; Zigman, Jeffrey M","year":2019,"journal":"Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 44(7), 1319-1327","doi":"10.1038/s41386-019-0334-7","pmid":"30758330","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04212","title":"Glucagon-like peptide 1 receptor agonists in type 1 diabetes mellitus.","authors":"Guyton, Justinne; Jeon, Michelle; Brooks, Amie","year":2019,"journal":"American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists, 76(21), 1739-1748","doi":"10.1093/ajhp/zxz179","pmid":"31612934","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04213","title":"Gastric pentadecapeptide body protection compound BPC 157 and its role in accelerating musculoskeletal soft tissue healing.","authors":"Gwyer, Daniel; Wragg, Nicholas M; Wilson, Samantha L","year":2019,"journal":"Cell and tissue research, 377(2), 153-159","doi":"10.1007/s00441-019-03016-8","pmid":"30915550","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"All published studies investigating BPC-157 have demonstrated consistently positive and prompt healing effects for various musculoskeletal soft tissue injuries, including tendon, ligament, and skeletal muscle damage. Benefits were observed for both traumatic (direct injury) and systemic insults, including hyperkalemia and hypermagnesemia.\n\nBPC-157 appears particularly promising for hypovascular and hypocellular tissues like tendons and ligaments that are notoriously difficult to heal. Few studies have reported adverse reactions to BPC-157 administration. However, the review identifies critical gaps: nearly all evidence comes from small rodent models, only a handful of research groups have conducted in-depth studies over the past two decades, and the precise healing mechanisms have not been fully elucidated. Human clinical data is absent.","whyItMatters":"Musculoskeletal soft tissue injuries — torn tendons, sprained ligaments, and muscle tears — represent an enormous social and economic burden. Current therapies often involve prolonged recovery or surgery. If BPC-157's consistent animal results translate to humans, it could provide a non-surgical treatment option that accelerates healing in tissues that traditionally heal slowly. The peptide's apparent safety profile and broad applicability across tissue types make it especially attractive.","specificNumbers":"","methodology":"This is a critical review article that systematically examined the published literature on BPC-157's effects on musculoskeletal soft tissue healing. The authors assessed studies across tendon, ligament, and skeletal muscle injury models, evaluated the quality and consistency of evidence, compared BPC-157 to other emerging growth factor-based therapies, and identified strengths and limitations in the current evidence base.","limitations":"The most significant limitation is the complete absence of human clinical trials. Nearly all studies come from a small number of research groups, raising concerns about independent replication. All evidence is from small rodent models that may not accurately predict human responses. The precise mechanisms of action are not fully understood. Dosing, timing, and optimal administration routes for clinical use have not been established. Long-term safety data, even in animals, is limited."},{"rthcId":"RPEP-04214","title":"Elevated Tear Human Neutrophil Peptides 1-3, Human Beta Defensin-2 Levels and Conjunctival Cathelicidin LL-37 Gene Expression in Ocular Rosacea.","authors":"Gökçınar, Nesrin Büyüktortop; Karabulut, Ayşe Anıl; Onaran, Zafer; Yumuşak, Erhan; Budak Yıldıran, Fatma Azize","year":2019,"journal":"Ocular immunology and inflammation, 27(7), 1174-1183","doi":"10.1080/09273948.2018.1504971","pmid":"30142005","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04215","title":"A leucine zipper-based peptide hybrid delivers functional Nanog protein inside the cell nucleus.","authors":"Hakata, Yoshiyuki; Michiue, Hiroyuki; Ohtsuki, Takashi; Miyazawa, Masaaki; Kitamatsu, Mizuki","year":2019,"journal":"Bioorganic & medicinal chemistry letters, 29(7), 878-881","doi":"10.1016/j.bmcl.2019.02.004","pmid":"30737088","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A pair of leucine zipper-based compounds was synthesized: Lz(E)-CPP (negatively charged zipper + cell-penetrating peptide) and Nanog-Lz(K) (positively charged zipper + cargo protein). When mixed at equimolar concentrations and applied to cells, the Nanog-Lz(K)/Lz(E)-CPP hybrid was successfully delivered into cells. Nanog protein reached the nucleus and exerted its proper transcriptional function after nuclear transport — demonstrating that the delivery system preserved protein activity.","whyItMatters":"Intracellular protein delivery is the holy grail of protein therapeutics — most therapeutic proteins can't cross cell membranes. This modular system is elegant because it separates the delivery mechanism (CPP) from the cargo (protein) using a universal leucine zipper 'adapter.' This means any protein could potentially be delivered by simply attaching Lz(K) to it, without redesigning the delivery vehicle each time. The fact that nuclear delivery preserves function is particularly important for transcription factor therapies.","specificNumbers":"","methodology":"Researchers chemically synthesized two complementary leucine zipper peptides: Lz(E) containing negatively charged residues and Lz(K) containing positively charged residues. Lz(E) was conjugated to a cell-penetrating peptide. Lz(K) was fused to recombinant Nanog protein. The components were mixed at equimolar ratios and applied to HeLa cells. Cellular uptake and nuclear localization were assessed, and Nanog's transcriptional function was confirmed.","limitations":"Very brief communication with limited experimental detail. Only one protein cargo (Nanog) was tested — generalizability to other proteins is assumed but not demonstrated. Only HeLa cells were used. Delivery efficiency (percentage of cells successfully transfected) was not quantified. Stability of the leucine zipper complex in serum or in vivo was not assessed. No comparison to other protein delivery methods was made. The study used a stem cell transcription factor as cargo, raising questions about safety if delivered to non-stem cells."},{"rthcId":"RPEP-04216","title":"Comparison of surgical versus diet-induced weight loss on appetite regulation and metabolic health outcomes.","authors":"Halliday, Tanya M; Polsky, Sarit; Schoen, Jonathan A; Legget, Kristina T; Tregellas, Jason R; Williamson, Kayla M; Cornier, Marc-Andre","year":2019,"journal":"Physiological reports, 7(7), e14048","doi":"10.14814/phy2.14048","pmid":"30927343","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"After matched 10 kg weight loss, the two groups showed strikingly different appetite peptide responses:\n\n• Fasting ghrelin decreased more after RYGB than diet (P=0.04)\n• Post-meal ghrelin AUC increased after dieting but not surgery (P=0.01)\n• Hunger AUC increased after diet but not RYGB (P<0.01)\n• Prospective food consumption AUC increased after diet vs RYGB (P<0.01)\n• Satiety AUC increased after RYGB but decreased after dieting (P<0.01)\n• Free fatty acid AUC increased more after RYGB (P=0.02)\n\nNotably, actual food intake at a test lunch decreased similarly in both groups, and fasting glucose and insulin improved equally — suggesting that the metabolic benefits of weight loss per se are independent of method, but appetite regulation is fundamentally different.","whyItMatters":"Weight regain is the Achilles' heel of diet-based obesity treatment, and appetite hormones are a key reason why. This study demonstrates that gastric bypass fundamentally rewires the appetite peptide response in ways that support sustained weight loss, while dieting triggers hormonal changes that actively promote weight regain. This explains the well-documented superiority of bariatric surgery for long-term weight maintenance and highlights why peptide-based approaches (like GLP-1 agonists) that mimic surgery's hormonal effects are so effective.","specificNumbers":"","methodology":"Adults qualifying for bariatric surgery were studied before and after 10 kg of weight loss through either Roux-en-Y gastric bypass (RYGB, n=6) or dietary restriction (DIET, n=17; 800 kcal/day liquid diet matching post-RYGB protocol). Appetite ratings (hunger, satiety, prospective food consumption) and appetite-related peptide hormones (ghrelin, PYY, GLP-1, insulin) plus metabolites (glucose, free fatty acids, triglycerides) were measured fasting and every 30 minutes for 3 hours after breakfast. Ad libitum food intake was measured at a test lunch.","limitations":"Very small sample sizes (RYGB n=6, DIET n=17) limit statistical power and generalizability. The groups were not randomized — patients chose surgery or were assigned to diet. The diet protocol (800 kcal liquid diet) does not represent typical weight loss approaches. Short-term assessment after 10 kg loss does not show whether the appetite differences persist. PYY and GLP-1 results are not detailed in the abstract despite being measured."},{"rthcId":"RPEP-04217","title":"Involvement of Substance P in the Analgesic Effect of Low-Level Laser Therapy in a Mouse Model of Chronic Widespread Muscle Pain.","authors":"Han, Der-Sheng; Lee, Cheng-Han; Shieh, Yih-Dar; Chen, Chih-Cheng","year":2019,"journal":"Pain medicine (Malden, Mass.), 20(10), 1963-1970","doi":"10.1093/pm/pnz056","pmid":"30908578","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"LLLT with 685 nm at 8 J/cm² effectively reduced mechanical hyperalgesia in the acid-induced chronic muscle pain (fibromyalgia) model. The analgesic effect was completely abolished by: (1) pretreatment with NK1 receptor antagonist RP-67580, (2) deletion of the Tac1 gene encoding Substance P (Tac1-/- mice), and (3) pretreatment with TRPV1 antagonist capsazepine. However, ASIC3 antagonist APETx2 did not block the effect.\n\nThis demonstrates that LLLT analgesia is mediated by intramuscular Substance P's antinociceptive (pain-reducing) signaling through NK1 receptors and involves TRPV1 activation — revealing an unexpected pain-relieving role for a neuropeptide traditionally associated with pain promotion.","whyItMatters":"LLLT is widely used for pain management but its mechanism has been poorly understood, limiting its acceptance and optimization. This study provides a specific molecular mechanism — Substance P acting in its paradoxical anti-pain role — that could guide more effective LLLT protocols. It also changes how we think about Substance P: rather than being exclusively pro-pain, it can also suppress pain depending on the context and location.","specificNumbers":"","methodology":"Researchers used the acid-induced chronic muscle pain model (a validated fibromyalgia model) in C57BL mice. Optimal LLLT dosage (685 nm, 8 J/cm²) was determined. Pharmacological interventions included NK1R antagonist (RP-67580), TRPV1 antagonist (capsazepine), and ASIC3 antagonist (APETx2). Genetic validation used Tac1 knockout mice lacking the Substance P gene. Mechanical hyperalgesia was assessed as the primary outcome.","limitations":"The study was conducted in mice using a chemical pain model; translation to human fibromyalgia may differ. Only one laser wavelength and dosage was tested. The mechanism by which LLLT activates intramuscular Substance P release was not determined. Whether this antinociceptive role of Substance P applies to other chronic pain conditions beyond the muscle pain model is unknown."},{"rthcId":"RPEP-04218","title":"Thymosin beta 4-Induced Autophagy Increases Cholinergic Signaling in PrP (106-126)-Treated HT22 Cells.","authors":"Han, Hye-Ju; Kim, Sokho; Kwon, Jungkee","year":2019,"journal":"Neurotoxicity research, 36(1), 58-65","doi":"10.1007/s12640-018-9985-0","pmid":"30552633","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In HT22 mouse hippocampal cells treated with toxic prion peptide PrP (106-126):\n\n- Tβ4 increased autophagy markers LC3A/B and Beclin1, protecting against prion-induced neurotoxicity\n- Tβ4 maintained balance between autophagy markers and AKT/mTOR pathway factors competitively against prion effects\n- Cholinergic signaling markers (ChTp and AChE) were preserved by Tβ4 against prion-induced disruption\n- All protective effects were reversed by 3-MA (autophagy inhibitor), confirming autophagy as the mechanism\n- Results demonstrate Tβ4 maintains cholinergic signaling through autophagy induction","whyItMatters":"Prion diseases have no effective treatment, and the cholinergic system is also damaged in Alzheimer's disease. Finding that a naturally occurring peptide can protect brain cells by activating cellular self-cleaning and preserving key brain signaling pathways opens potential therapeutic avenues for multiple neurodegenerative diseases, not just prion disease.","specificNumbers":"","methodology":"HT22 mouse hippocampal cells were treated with the toxic prion peptide fragment PrP (106-126) with and without thymosin beta-4. Autophagy markers (LC3A/B, Beclin1), autophagy pathway proteins (AKT, p-AKT, mTOR, p-mTOR), and cholinergic signaling markers (ChTp, AChE) were measured. The autophagy inhibitor 3-MA was used to confirm the mechanism. Protein expression was assessed by Western blot.","limitations":"This was an in vitro study using a single mouse hippocampal cell line (HT22), which may not reflect the complexity of prion disease in the living brain. The prion peptide fragment PrP (106-126) is a model of prion toxicity but may not capture all aspects of actual prion disease. Concentrations used in cell culture may not correspond to achievable tissue levels in vivo. No animal model of prion disease was tested."},{"rthcId":"RPEP-04219","title":"An effective mouse model for adoptive cancer immunotherapy targeting neoantigens.","authors":"Hanada, Ken-Ichi; Yu, Zhiya; Chappell, Gabrielle R; Park, Adam S; Restifo, Nicholas P","year":2019,"journal":"JCI insight, 4(10)","doi":"10.1172/jci.insight.124405","pmid":"31092734","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"T cells from pmel-1 transgenic mice targeting the mutated (neoantigen) version of the gp100 peptide showed enhanced recognition as measured by IFN-γ production. When used in adoptive cell transfer, neoantigen-targeting T cells achieved complete and durable regression of large, established, vascularized B16 melanoma tumors.\n\nCritically, neoantigen targeting required less lymphodepleting conditioning than targeting the wild-type peptide, suggesting reduced treatment toxicity. The study also uncovered that enforced expression of the IL-2 receptor alpha chain (CD25) on mutation-reactive CD8+ T cells further improved their anti-tumor function, revealing a new strategy for enhancing neoantigen-targeted immunotherapy.","whyItMatters":"Adoptive T cell therapy has shown remarkable results in some cancer patients, but its effectiveness and toxicity vary widely. This study provides a preclinical model demonstrating that targeting mutated neoantigens — rather than normal self-proteins — can improve both effectiveness and safety. The reduced need for toxic lymphodepletion is particularly significant, as pre-treatment conditioning is one of the major barriers to wider clinical adoption of cell-based immunotherapy.","specificNumbers":"","methodology":"Researchers used pmel-1 T cell receptor-transgenic mice whose T cells recognize the gp100 peptide. B16 melanoma cells were gene-engineered to express either wild-type or mutated gp100 epitopes. Adoptive cell transfer experiments were conducted in tumor-bearing mice with varying levels of lymphodepleting conditioning. T cell recognition was measured by IFN-γ production. The effect of enforced CD25 expression on CD8+ T cell anti-tumor function was also evaluated.","limitations":"This is a mouse model study using a transgenic system with a single known neoantigen, which is far simpler than human cancers with many mutations. The B16 melanoma model is well-characterized but may not represent the diversity of human tumor types. The engineered neoantigen expression may not fully replicate natural neoantigen presentation in human cancers. Translation to human clinical settings requires identifying patient-specific neoantigens, which remains technically challenging."},{"rthcId":"RPEP-04220","title":"Discovery of O-glycans on atrial natriuretic peptide (ANP) that affect both its proteolytic degradation and potency at its cognate receptor.","authors":"Hansen, Lasse H; Madsen, Thomas Daugbjerg; Goth, Christoffer K; Clausen, Henrik; Chen, Yang; Dzhoyashvili, Nina; Iyer, Seethalakshmi R; Sangaralingham, S Jeson; Burnett, John C; Rehfeld, Jens F; Vakhrushev, Sergey Y; Schjoldager, Katrine T; Goetze, Jens P","year":2019,"journal":"The Journal of biological chemistry, 294(34), 12567-12578","doi":"10.1074/jbc.RA119.008102","pmid":"31186350","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04221","title":"Synergy and remarkable specificity of antimicrobial peptides in vivo using a systematic knockout approach.","authors":"Hanson, Mark Austin; Dostálová, Anna; Ceroni, Camilla; Poidevin, Mickael; Kondo, Shu; Lemaitre, Bruno","year":2019,"journal":"eLife, 8","doi":"10.7554/eLife.44341","pmid":"30803481","tags":[],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"Using CRISPR to systematically knock out all 14 immune-inducible antimicrobial peptide (AMP) genes in Drosophila — including attacins, cecropins, diptericins, drosocin, drosomycin, metchnikowin, and defensin — researchers demonstrated that AMPs are essential for in vivo defense against Gram-negative bacteria and fungi.\n\nCritically, the study revealed remarkable specificity: individual AMPs contributed the majority of killing activity against specific pathogens, rather than all AMPs working equally against all microbes. AMPs also worked synergistically — combinations were more effective than predicted from individual contributions. Flies lacking all 14 AMPs were highly susceptible to infections.","whyItMatters":"For decades, AMP research relied on lab dish (in vitro) experiments that didn't prove AMPs actually mattered inside living organisms. This landmark eLife study is the first to systematically eliminate every known AMP in an animal and test what happens with real infections. The finding that individual AMPs have specific pathogen targets — rather than being generic antimicrobials — fundamentally changes how we think about designing AMP-based drugs and understanding natural immunity.","specificNumbers":"14 AMP genes knocked out · 4 Attacins · 4 Cecropins · 2 Diptericins · Drosocin · Drosomycin · Metchnikowin · Defensin · Tested against diverse bacteria + fungi · Synergistic and additive effects demonstrated","methodology":"Used CRISPR gene editing to create individual, combination, and complete AMP knockout Drosophila flies (fruit flies lacking all 14 known immune-inducible AMPs). Challenged knockout flies with diverse Gram-negative bacteria, Gram-positive bacteria, and fungal pathogens. Measured survival and pathogen load to determine each AMP's contribution to defense against each pathogen.","limitations":"Drosophila AMPs are not identical to human AMPs, so specific pathogen-AMP matchings won't directly translate. Fruit flies lack adaptive immunity, making AMPs relatively more important than in mammals where antibodies also fight infection. Only immune-inducible AMPs were targeted; constitutively expressed peptides may also contribute. The controlled lab infection conditions differ from natural pathogen exposure."},{"rthcId":"RPEP-04222","title":"A Novel Botulinum Toxin TAT-EGFP-HCS Fusion Protein Capable of Specific Delivery Through the Blood-brain Barrier to the Central Nervous System.","authors":"Hao, Fengjin; Feng, Yueqin; Guan, Yifu","year":2019,"journal":"CNS & neurological disorders drug targets, 18(1), 37-43","doi":"10.2174/1871527317666181011113215","pmid":"30318007","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04223","title":"Calcitonin Gene-Related Peptide Modulators - The History and Renaissance of a New Migraine Drug Class.","authors":"Hargreaves, Richard; Olesen, Jes","year":2019,"journal":"Headache, 59(6), 951-970","doi":"10.1111/head.13510","pmid":"31020659","tags":[],"studyType":"Review","evidenceStrength":"strong","keyFinding":"CGRP (calcitonin gene-related peptide) has been definitively proven as a central driver of migraine through decades of converging evidence: anatomical colocalization with pain-producing meningeal blood vessels, elevated levels during migraine attacks, intravenous CGRP triggering migraines only in migraineurs, and clinical efficacy of drugs blocking CGRP.\n\nCritically, PET imaging studies showed that CGRP receptor antagonists achieved no brain receptor occupancy at effective antimigraine doses — proving the therapeutic action is peripheral, not central. This revolutionized migraine understanding: migraine pain is at least partly peripheral in origin.\n\nTwo drug classes have emerged from this science: (1) monoclonal antibodies given by injection that neutralize CGRP peptide (fremanezumab, galcanezumab, eptinezumab) or block its receptor (erenumab) for migraine prevention; and (2) oral small-molecule CGRP receptor antagonists (gepants) for both acute treatment (ubrogepant, rimegepant) and prevention (atogepant). All have shown consistent efficacy in large, multicenter RCTs.","whyItMatters":"The CGRP migraine story is one of the greatest successes in peptide-based drug development. It took the field from a peptide discovered in sensory nerves to multiple FDA-approved drugs in two different drug classes — all within a few decades. This represents a complete bench-to-bedside arc: peptide biology → disease mechanism → drug target → approved therapeutics. It also fundamentally changed how scientists understand migraine — from a brain disorder to one with a significant peripheral peptide component.","specificNumbers":"4 approved anti-CGRP antibodies (erenumab, fremanezumab, galcanezumab, eptinezumab) · 3 approved gepants (ubrogepant, rimegepant, atogepant) · PET showed 0 brain receptor occupancy at effective doses · IV CGRP triggers migraine only in migraineurs","methodology":"Comprehensive narrative review published in Headache, the official journal of the American Headache Society. Chronicles the scientific history of CGRP in migraine from anatomical discovery through translational studies, clinical trials of small molecule antagonists, PET imaging proof-of-mechanism, and the development and approval of anti-CGRP antibodies and gepants.","limitations":"Published in 2019, so does not cover the most recent clinical data and real-world experience with anti-CGRP drugs. As a review by key figures in the field, it presents an advocacy perspective for CGRP-based approaches. Long-term safety data for anti-CGRP therapies was still limited at time of publication."},{"rthcId":"RPEP-04224","title":"Mechanisms of GLP-1 receptor-independent renoprotective effects of the dipeptidyl peptidase type 4 inhibitor linagliptin in GLP-1 receptor knockout mice with 5/6 nephrectomy.","authors":"Hasan, Ahmed A; von Websky, Karoline; Reichetzeder, Christoph; Tsuprykov, Oleg; Gaballa, Mohamed M S; Guo, Jingli; Zeng, Shufei; Delić, Denis; Tammen, Harald; Klein, Thomas; Kleuser, Burkhard; Hocher, Berthold","year":2019,"journal":"Kidney international, 95(6), 1373-1388","doi":"10.1016/j.kint.2019.01.010","pmid":"30979564","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04225","title":"Development of Organelle Replacement Therapy Using a Stearyl-Polyhistidine Peptide against Lysosomal Storage Disease Cells.","authors":"Hayashi, Taiki; Okamoto, Riku; Kawano, Tsuyoshi; Iwasaki, Takashi","year":2019,"journal":"Molecules (Basel, Switzerland), 24(16)","doi":"10.3390/molecules24162995","pmid":"31426598","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04226","title":"Stereoselective pH Responsive Peptide Dendrimers for siRNA Transfection.","authors":"Heitz, Marc; Javor, Sacha; Darbre, Tamis; Reymond, Jean-Louis","year":2019,"journal":"Bioconjugate chemistry, 30(8), 2165-2182","doi":"10.1021/acs.bioconjchem.9b00403","pmid":"31398014","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04227","title":"A Case Study to Identify the Drug Conjugation Site of a Site-Specific Antibody-Drug-Conjugate Using Middle-Down Mass Spectrometry.","authors":"Hernandez-Alba, Oscar; Houel, Stéphane; Hessmann, Steve; Erb, Stéphane; Rabuka, David; Huguet, Romain; Josephs, Jonathan; Beck, Alain; Drake, Penelope M; Cianférani, Sarah","year":2019,"journal":"Journal of the American Society for Mass Spectrometry, 30(11), 2419-2429","doi":"10.1007/s13361-019-02296-2","pmid":"31429052","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04228","title":"SOCS1-Derived Peptide Administered by Eye Drops Prevents Retinal Neuroinflammation and Vascular Leakage in Experimental Diabetes.","authors":"Hernández, Cristina; Bogdanov, Patricia; Gómez-Guerrero, Carmen; Sampedro, Joel; Solà-Adell, Cristina; Espejo, Carmen; García-Ramírez, Marta; Prieto, Ignacio; Egido, Jesús; Simó, Rafael","year":2019,"journal":"International journal of molecular sciences, 20(15)","doi":"10.3390/ijms20153615","pmid":"31344857","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04229","title":"A Tumor-Peptide-Based Nanoparticle Vaccine Elicits Efficient Tumor Growth Control in Antitumor Immunotherapy.","authors":"Heße, Carolin; Kollenda, Sebastian; Rotan, Olga; Pastille, Eva; Adamczyk, Alexandra; Wenzek, Christina; Hansen, Wiebke; Epple, Matthias; Buer, Jan; Westendorf, Astrid M; Knuschke, Torben","year":2019,"journal":"Molecular cancer therapeutics, 18(6), 1069-1080","doi":"10.1158/1535-7163.MCT-18-0764","pmid":"30962317","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04230","title":"Milk in the prevention and management of type 2 diabetes: The potential role of milk proteins.","authors":"Hidayat, Khemayanto; Du, Xuan; Shi, Bi-Min","year":2019,"journal":"Diabetes/metabolism research and reviews, 35(8), e3187","doi":"10.1002/dmrr.3187","pmid":"31111646","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review establishes three primary mechanisms by which milk protein-derived peptides lower postprandial glucose. First, they delay gastric emptying, slowing the rate at which carbohydrates enter the small intestine. Second, they enhance incretin hormone responses — particularly GLP-1 and GIP — which are the same hormones mimicked by blockbuster diabetes drugs like semaglutide. Third, they directly increase postprandial insulin secretion.\n\nThese effects have been demonstrated in both healthy subjects and patients with type 2 diabetes. The bioactive peptides released during milk protein digestion are the proposed mediators, creating a physiological milieu that naturally amplifies the body's blood sugar control mechanisms.","whyItMatters":"With type 2 diabetes projected to affect over 1.3 billion people by 2050, dietary interventions that can complement or even partially replace pharmaceutical approaches are urgently needed. Milk proteins are safe, widely available, and inexpensive compared to GLP-1 drugs. The finding that they work partly through the same incretin pathway targeted by semaglutide and tirzepatide suggests a natural, food-based approach to blood sugar management that could be accessible to populations without access to expensive peptide medications.","specificNumbers":"","methodology":"This is a narrative review summarizing evidence from epidemiological studies linking dairy consumption to diabetes risk, clinical trials of milk protein supplementation on postprandial glucose and insulin responses, and mechanistic studies identifying bioactive peptides and their targets.","limitations":"As a narrative review, the paper may not comprehensively capture all available evidence or assess studies for bias. The exact contribution of milk proteins versus other dairy nutrients (calcium, vitamin D, fat) to diabetes risk reduction is difficult to disentangle. The bioavailability and potency of milk-derived bioactive peptides in vivo remain uncertain. Individual variation in milk protein digestion (affected by lactose tolerance, gut microbiome, and proteolytic enzyme activity) could significantly affect outcomes. The review does not quantify the magnitude of glucose-lowering effects compared to pharmaceutical interventions."},{"rthcId":"RPEP-04231","title":"The Limitations of Collagen/CPP Hybrid Peptides as Carriers for Cancer Drugs to FaDu Cells.","authors":"Ho, Kevin; Morfin, Cristobal; Slowinska, Katarzyna","year":2019,"journal":"Molecules (Basel, Switzerland), 24(4)","doi":"10.3390/molecules24040676","pmid":"30769789","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04232","title":"Effect of neurokinin-1-receptor blockage on fracture healing in rats.","authors":"Hofman, Martijn; Rabenschlag, Frederik; Andruszkow, Hagen; Andruszkow, Julia; Möckel, Diana; Lammers, Twan; Kolejewska, Aneta; Kobbe, Philipp; Greven, Johannes; Teuben, Michel Paul Johan; Poeze, Martijn; Hildebrand, Frank","year":2019,"journal":"Scientific reports, 9(1), 9744","doi":"10.1038/s41598-019-46278-6","pmid":"31278316","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04233","title":"Cardiovascular outcome trials of glucose-lowering medications: an update.","authors":"Home, Philip","year":2019,"journal":"Diabetologia, 62(3), 357-369","doi":"10.1007/s00125-018-4801-1","pmid":"30607467","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04234","title":"Membrane potential is vital for rapid permeabilization of plasma membranes and lipid bilayers by the antimicrobial peptide lactoferricin B.","authors":"Hossain, Farzana; Moghal, Md Mizanur Rahman; Islam, Md Zahidul; Moniruzzaman, Md; Yamazaki, Masahito","year":2019,"journal":"The Journal of biological chemistry, 294(27), 10449-10462","doi":"10.1074/jbc.RA119.007762","pmid":"31118274","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04235","title":"Systematic mutational analysis of human neutrophil α-defensin HNP4.","authors":"Hu, Han; Di, Bin; Tolbert, William D; Gohain, Neelakshi; Yuan, Weirong; Gao, Pan; Ma, Bohan; He, Qigai; Pazgier, Marzena; Zhao, Le; Lu, Wuyuan","year":2019,"journal":"Biochimica et biophysica acta. Biomembranes, 1861(4), 835-844","doi":"10.1016/j.bbamem.2019.01.007","pmid":"30658057","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04236","title":"Improved Intracellular Delivery of Polyarginine Peptides with Cargoes.","authors":"Hu, Juanmei; Lou, Yimin; Wu, Fengmin","year":2019,"journal":"The journal of physical chemistry. B, 123(12), 2636-2644","doi":"10.1021/acs.jpcb.8b10483","pmid":"30830784","tags":["drug-delivery","cell-penetrating-peptides"],"studyType":"computational","evidenceStrength":"preliminary","keyFinding":"Using computer simulations, researchers discovered that polyarginine (R8) cell-penetrating peptides enter cells by punching temporary water pores through the cell membrane. When these peptides were attached to small nanoparticle cargoes via linkers, their delivery efficiency actually improved — the nanoparticles extended the lifetime of the water pore, giving more peptide-cargo complexes time to pass through.\n\nCritically, linker length was the key design variable. Maximum delivery efficiency occurred when the linker was about half the thickness of the cell membrane. Linkers that were too long caused two problems: they blocked the water pore with the nanoparticle cargo, reducing delivery, and they could leave the pore open too long, potentially killing the cell. This provides a clear design rule for engineering peptide-drug conjugates.","whyItMatters":"Cell-penetrating peptides are one of the most promising tools for getting drugs inside cells, but attaching cargoes to them often reduces their ability to cross the membrane. This study reveals the physical mechanism behind that problem and provides a specific design principle — optimal linker length equals half the membrane thickness — that could guide the engineering of more effective peptide-drug conjugates with lower toxicity.","specificNumbers":"R8 (8-arginine) peptide · Optimal linker length: ~half membrane thickness · Coarse-grained molecular dynamics simulation · Water pore mechanism · Nanoparticle cargo conjugates","methodology":"The researchers used coarse-grained molecular dynamics (MD) simulations to model how polyarginine R8 peptides interact with and cross lipid bilayer membranes, both alone and when conjugated to small nanoparticle cargoes. They systematically varied linker lengths between the peptide and nanoparticle to determine the effect on translocation efficiency and membrane integrity. The simulations tracked water pore formation, lipid rearrangement, and peptide movement at the molecular level.","limitations":"This is a computational study using simplified (coarse-grained) molecular models that approximate but do not perfectly replicate real cell membranes. The simulated membrane lacks the complexity of actual cell surfaces (no proteins, sugars, or cholesterol variations). The findings have not been experimentally validated in real cells. The nanoparticle cargoes used in simulations are idealized spheres, whereas real drug cargoes have diverse shapes and chemistries."},{"rthcId":"RPEP-04237","title":"Kisspeptin as a potential biomarker throughout pregnancy.","authors":"Hu, Kai-Lun; Zhao, Hongcui; Yu, Yang; Li, Rong","year":2019,"journal":"European journal of obstetrics, gynecology, and reproductive biology, 240, 261-266","doi":"10.1016/j.ejogrb.2019.07.016","pmid":"31344665","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Plasma kisspeptin levels rise significantly throughout pregnancy, primarily produced by the placenta. The review found that kisspeptin levels could serve as a biomarker for detecting miscarriage risk, pre-eclampsia, gestational trophoblastic neoplasia (GTN), and fetal development problems. Kisspeptin may also play a role in triggering labor by stimulating oxytocin secretion during term pregnancy.","whyItMatters":"Early detection of pregnancy complications like miscarriage and pre-eclampsia can save lives, but current biomarkers are imperfect. Kisspeptin offers a new window into placental health that could be measured with a simple blood test. If validated, kisspeptin levels could give doctors an earlier warning of pregnancy problems, enabling earlier intervention.","specificNumbers":"","methodology":"This is a narrative review of published studies examining kisspeptin levels during pregnancy. The authors synthesized evidence on kisspeptin's role as a placental hormone, its trajectory across trimesters, and its associations with pregnancy complications including miscarriage, pre-eclampsia, and gestational trophoblastic neoplasia.","limitations":"As a narrative review, the paper does not perform quantitative pooling of data. The studies reviewed varied in sample sizes, measurement methods, and kisspeptin assays used, making direct comparisons difficult. Standardized reference ranges for kisspeptin across pregnancy have not been established. The mechanism linking kisspeptin levels to specific complications is not fully understood."},{"rthcId":"RPEP-04238","title":"Deoxynivalenol decreased intestinal immune function related to NF-κB and TOR signalling in juvenile grass carp (Ctenopharyngodon idella).","authors":"Huang, Chen; Feng, Lin; Jiang, Wei-Dan; Wu, Pei; Liu, Yang; Zeng, Yun-Yun; Jiang, Jun; Kuang, Sheng-Yao; Tang, Ling; Zhou, Xiao-Qiu","year":2019,"journal":"Fish & shellfish immunology, 84, 470-484","doi":"10.1016/j.fsi.2018.10.039","pmid":"30339843","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04239","title":"RNA Display Methods for the Discovery of Bioactive Macrocycles.","authors":"Huang, Yichao; Wiedmann, Mareike Margarete; Suga, Hiroaki","year":2019,"journal":"Chemical reviews, 119(17), 10360-10391","doi":"10.1021/acs.chemrev.8b00430","pmid":"30395448","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04240","title":"HcCUB-Lec, a newly identified C-type lectin that contains a distinct CUB domain and participates in the immune defense of the triangle sail mussel Hyriopsis cumingii.","authors":"Huang, Ying; Ren, Qian","year":2019,"journal":"Developmental and comparative immunology, 93, 66-77","doi":"10.1016/j.dci.2018.12.012","pmid":"30590065","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04241","title":"Molecular Characterization of Two Toll Receptors in Hyriopsis cumingii and Their Potential Roles in Antibacterial Response.","authors":"Huang, Ying; Zhang, Guosong; Ren, Qian","year":2019,"journal":"Frontiers in physiology, 10, 952","doi":"10.3389/fphys.2019.00952","pmid":"31404151","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04242","title":"Method development of a novel PK assay for antibody-conjugated drug measurement of ADCs using peptide-linker drug analyte.","authors":"Hyung, Suk-Joon; Li, Dongwei; Koppada, Neelima; Kaur, Surinder; Saad, Ola M","year":2019,"journal":"Analytical and bioanalytical chemistry, 411(12), 2587-2596","doi":"10.1007/s00216-019-01701-9","pmid":"30828756","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04243","title":"Effect of Neprilysin Inhibition on Various Natriuretic Peptide Assays.","authors":"Ibrahim, Nasrien E; McCarthy, Cian P; Shrestha, Shreya; Gaggin, Hanna K; Mukai, Renata; Szymonifka, Jackie; Apple, Fred S; Burnett, John C; Iyer, Seethalakshmi; Januzzi, James L","year":2019,"journal":"Journal of the American College of Cardiology, 73(11), 1273-1284","doi":"10.1016/j.jacc.2018.12.063","pmid":"30898202","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04244","title":"Medicinal Potentialities of Plant Defensins: A Review with Applied Perspectives.","authors":"Ishaq, Nida; Bilal, Muhammad; Iqbal, Hafiz M N","year":2019,"journal":"Medicines (Basel, Switzerland), 6(1)","doi":"10.3390/medicines6010029","pmid":"30791451","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04245","title":"Design, Synthesis, and Evaluation of Lipopeptide Conjugates of Mercaptoundecahydrododecaborate for Boron Neutron Capture Therapy.","authors":"Isono, Aoi; Tsuji, Mieko; Sanada, Yu; Matsushita, Akari; Masunaga, Shinichiro; Hirayama, Tasuku; Nagasawa, Hideko","year":2019,"journal":"ChemMedChem, 14(8), 823-832","doi":"10.1002/cmdc.201800793","pmid":"30707500","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04246","title":"Recent advances in vasoactive intestinal peptide physiology and pathophysiology: focus on the gastrointestinal system.","authors":"Iwasaki, Mari; Akiba, Yasutada; Kaunitz, Jonathan D","year":2019,"journal":"F1000Research, 8","doi":"10.12688/f1000research.18039.1","pmid":"31559013","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04247","title":"Rapid and Scalable Plant-Based Production of a Potent Plasmin Inhibitor Peptide.","authors":"Jackson, Mark A; Yap, Kuok; Poth, Aaron G; Gilding, Edward K; Swedberg, Joakim E; Poon, Simon; Qu, Haiou; Durek, Thomas; Harris, Karen; Anderson, Marilyn A; Craik, David J","year":2019,"journal":"Frontiers in plant science, 10, 602","doi":"10.3389/fpls.2019.00602","pmid":"31156672","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04248","title":"Complex macrocycle exploration: parallel, heuristic, and constraint-based conformer generation using ForceGen.","authors":"Jain, Ajay N; Cleves, Ann E; Gao, Qi; Wang, Xiao; Liu, Yizhou; Sherer, Edward C; Reibarkh, Mikhail Y","year":2019,"journal":"Journal of computer-aided molecular design, 33(6), 531-558","doi":"10.1007/s10822-019-00203-1","pmid":"31054028","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04249","title":"A review on parenteral delivery of peptides and proteins.","authors":"Jain, Divisha; Mahammad, S Shahe; Singh, Pirthi Pal; Kodipyaka, Ravinder","year":2019,"journal":"Drug development and industrial pharmacy, 45(9), 1403-1420","doi":"10.1080/03639045.2019.1628770","pmid":"31215293","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04250","title":"Invited Commentary on Preventive Anti-Migraine Therapy (PAMT).","authors":"Jain, Sameer; Silberstein, Stephen D","year":2019,"journal":"Current treatment options in neurology, 21(4), 14","doi":"10.1007/s11940-019-0555-4","pmid":"30868470","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04251","title":"ISSLS Prize in Basic science 2019: Physical activity attenuates fibrotic alterations to the multifidus muscle associated with intervertebral disc degeneration.","authors":"James, G; Klyne, D M; Millecamps, M; Stone, L S; Hodges, P W","year":2019,"journal":"European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society, 28(5), 893-904","doi":"10.1007/s00586-019-05902-9","pmid":"30737621","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04252","title":"Mycoplasma hyopneumoniae surface-associated proteases cleave bradykinin, substance P, neurokinin A and neuropeptide Y.","authors":"Jarocki, Veronica Maria; Raymond, Benjamin Bernard Armando; Tacchi, Jessica Leigh; Padula, Matthew Paul; Djordjevic, Steven Philip","year":2019,"journal":"Scientific reports, 9(1), 14585","doi":"10.1038/s41598-019-51116-w","pmid":"31601981","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04253","title":"Bioactive cell penetrating peptides and proteins in cancer: a bright future ahead.","authors":"Jauset, Toni; Beaulieu, Marie-Eve","year":2019,"journal":"Current opinion in pharmacology, 47, 133-140","doi":"10.1016/j.coph.2019.03.014","pmid":"31048179","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04254","title":"The emerging role of substance P/neurokinin-1 receptor signaling pathways in growth and development of tumor cells.","authors":"Javid, Hossein; Mohammadi, Fariba; Zahiri, Elnaz; Hashemy, Seyed Isaac","year":2019,"journal":"Journal of physiology and biochemistry, 75(4), 415-421","doi":"10.1007/s13105-019-00697-1","pmid":"31372898","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04255","title":"Pharmacological inhibition of Bax-induced cell death: Bax-inhibiting peptides and small compounds inhibiting Bax.","authors":"Jensen, Kelsey; WuWong, David Jasen; Wong, Sean; Matsuyama, Mieko; Matsuyama, Shigemi","year":2019,"journal":"Experimental biology and medicine (Maywood, N.J.), 244(8), 621-629","doi":"10.1177/1535370219833624","pmid":"30836793","tags":[],"studyType":"review","evidenceStrength":"low","keyFinding":"This mini-review surveys all known Bax inhibitors — peptides, small molecules, and antibodies — that can prevent mitochondria-dependent programmed cell death (apoptosis). While drugs that activate Bax have been developed for cancer treatment (to kill tumor cells), no clinically effective therapeutics have been developed that suppress Bax-induced cell death to rescue essential cells in conditions like neurodegeneration, retinal degeneration, stroke, organ preservation, and lung fibrosis.\n\nBax-inhibiting peptides (BIPs) represent a key class of these inhibitors, delivered via cell-penetrating peptide technology to reach mitochondrial membranes where Bax exerts its cell-killing activity.","whyItMatters":"Bax is a master switch for cell death — when it's activated inappropriately, essential cells die in diseases like Parkinson's, retinal degeneration, and stroke. Having peptide inhibitors that can block this cell death pathway could protect neurons, retinal cells, and transplanted organs. This review maps the landscape of what's been tried and what's needed to make these inhibitors clinically useful.","specificNumbers":"Bax inhibitor classes: peptides, small molecules, antibodies · Potential applications: neurodegeneration, brain ischemia, retinal degeneration, organ preservation, pulmonary fibrosis","methodology":"Mini-review summarizing previously reported Bax inhibitors across three categories (peptides, small compounds, antibodies), discussing their mechanisms, potential applications, and future research directions.","limitations":"This is a narrative mini-review with a brief abstract, not a systematic review. No new data is presented. The abstract doesn't detail specific peptide structures, efficacy data, or the current development stage of any Bax inhibitor."},{"rthcId":"RPEP-04256","title":"The role of glucagon-like peptide-1 in reproduction: from physiology to therapeutic perspective.","authors":"Jensterle, Mojca; Janez, Andrej; Fliers, Eric; DeVries, J Hans; Vrtacnik-Bokal, Eda; Siegelaar, Sarah E","year":2019,"journal":"Human reproduction update, 25(4), 504-517","doi":"10.1093/humupd/dmz019","pmid":"31260047","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04257","title":"VGF and its C-terminal peptide TLQP-62 in ventromedial prefrontal cortex regulate depression-related behaviors and the response to ketamine.","authors":"Jiang, Cheng; Lin, Wei-Jye; Labonté, Benoit; Tamminga, Carol A; Turecki, Gustavo; Nestler, Eric J; Russo, Scott J; Salton, Stephen R","year":2019,"journal":"Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 44(5), 971-981","doi":"10.1038/s41386-018-0277-4","pmid":"30504797","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04258","title":"Association between thymosin beta4 and non-alcoholic fatty liver disease.","authors":"Jiang, Yong; Zhang, Ying; Ma, Cui-Hua; Zhang, Zhi-Guang; Li, Man; Ji, Ying-Lan; Qi, Feng-Xiang","year":2019,"journal":"Revista espanola de enfermedades digestivas, 111(4), 308-313","doi":"10.17235/reed.2019.5927/2018","pmid":"30896961","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Serum thymosin beta-4 was significantly lower in NAFLD patients (3.20 ± 0.98 mg/L) compared to healthy controls (5.53 ± 1.24 mg/L), a 42% reduction (P<0.001).\n\nMultivariate logistic regression identified Tβ4 as an independent predictor of NAFLD (OR=0.343, 95% CI 0.240-0.491, P<0.001), meaning higher Tβ4 levels were strongly protective. Other independent predictors were LDL cholesterol, ALT, and IL-6.\n\nTβ4 showed significant negative correlations with total cholesterol (r=-0.163), triglycerides (r=-0.253), AST (r=-0.143), GGT (r=-0.245), and IL-6 (r=-0.155). Tβ4 was positively correlated with adiponectin (r=0.143), an anti-inflammatory and insulin-sensitizing hormone.","whyItMatters":"NAFLD affects roughly 25% of the global population and can progress to serious liver disease including cirrhosis and liver cancer. There is currently no approved drug treatment for NAFLD. Thymosin beta-4 is known for its tissue-healing and anti-inflammatory properties, and this finding that it's depleted in fatty liver disease suggests it could be both a diagnostic biomarker and a potential therapeutic target. If Tβ4 supplementation could prevent or reverse fatty liver, it would address an enormous unmet medical need.","specificNumbers":"","methodology":"Case-control study with 76 NAFLD patients and 130 healthy controls. Serum levels of Tβ4, IL-6, and adiponectin were measured by ELISA. Standard clinical measurements included fasting glucose, insulin, lipid profiles, and liver function tests. Multivariate logistic regression identified independent predictors of NAFLD. Correlation analyses assessed relationships between Tβ4 and metabolic, inflammatory, and liver function markers.","limitations":"This is a cross-sectional case-control study, so it cannot determine whether low Tβ4 causes NAFLD or is a consequence of liver disease. The sample size is moderate (206 total) and from a single center. NAFLD diagnosis and severity staging methods are not detailed in the abstract. The correlation coefficients, while statistically significant, are relatively weak (r values of -0.14 to -0.25), suggesting Tβ4 explains only a small portion of the metabolic variance. The study did not assess whether Tβ4 supplementation would improve NAFLD."},{"rthcId":"RPEP-04259","title":"Bromotryptophan and its Analogs in Peptides from Marine Animals.","authors":"Jimenez, Elsie C","year":2019,"journal":"Protein and peptide letters, 26(4), 251-260","doi":"10.2174/0929866526666190119170020","pmid":"30663557","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04260","title":"Human antimicrobial peptides and cancer.","authors":"Jin, Ge; Weinberg, Aaron","year":2019,"journal":"Seminars in cell & developmental biology, 88, 156-162","doi":"10.1016/j.semcdb.2018.04.006","pmid":"29694838","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04261","title":"Saccharomyces cerevisiae β-glucan-induced SBD-1 expression in ovine ruminal epithelial cells is mediated through the TLR-2-MyD88-NF-κB/MAPK pathway.","authors":"Jin, Xin; Zhang, Man; Yang, Yin-Feng","year":2019,"journal":"Veterinary research communications, 43(2), 77-89","doi":"10.1007/s11259-019-09747-x","pmid":"30863917","tags":["defensins","innate-immunity"],"studyType":"laboratory-study","evidenceStrength":"moderate","keyFinding":"Beta-glucan from yeast (Saccharomyces cerevisiae) triggers sheep ruminal epithelial cells to produce the antimicrobial peptide sheep beta-defensin-1 (SBD-1) through a specific signaling pathway: TLR-2 → MyD88 → NF-κB/MAPK.\n\nWhen researchers knocked down TLR-2 or MyD88, beta-glucan-induced SBD-1 production dropped significantly. Blocking either the MAPK or NF-κB pathways also reduced SBD-1 expression, but NF-κB inhibition had the larger effect, suggesting it's the dominant pathway controlling defensin production in response to yeast components.\n\nThis means the gut lining of sheep actively recognizes yeast cell wall components through innate immune receptors and responds by ramping up antimicrobial peptide production — explaining part of how probiotic yeasts boost gut defense.","whyItMatters":"Probiotics containing yeast are widely used in livestock nutrition, but the molecular mechanisms behind their immune-boosting effects have been unclear. This study maps out exactly how a yeast component triggers antimicrobial peptide production in gut cells. Understanding this pathway could lead to more targeted probiotic strategies in veterinary medicine and has broader implications for how beta-glucans stimulate defensin production across species, including potentially humans.","specificNumbers":"TLR-2 + MyD88 knockdown attenuated SBD-1 expression · NF-κB pathway = dominant signaling route · MAPK pathway = secondary contributor","methodology":"In vitro study using cultured ovine ruminal epithelial cells (ORECs). Beta-glucan was applied to stimulate cells. SBD-1 expression was measured by qPCR and ELISA. Western blotting assessed pathway activation. TLR-2 and MyD88 were knocked down or inhibited to test their necessity. MAPK and NF-κB pathways were blocked with specific inhibitors to determine their contributions.","limitations":"In vitro cell culture study using sheep ruminal epithelial cells — results may not directly translate to whole-animal gut immunity. Only one defensin (SBD-1) was studied. The relative contributions of NF-κB vs. MAPK pathways may differ in other cell types or species. No in vivo validation was performed."},{"rthcId":"RPEP-04262","title":"Cloning, Expression and Effects of P. americana Thymosin on Wound Healing.","authors":"Jing, Jie; Sun, Xiaohong; Zhou, Chuang; Zhang, Yifan; Shen, Yongmei; Zeng, Xiaomao; Yue, Bisong; Zhang, Xiuyue","year":2019,"journal":"International journal of molecular sciences, 20(19)","doi":"10.3390/ijms20194932","pmid":"31590392","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04263","title":"A Relative Cost of Control Analysis of Once-Weekly Semaglutide Versus Exenatide Extended-Release and Dulaglutide for Bringing Patients to HbA1c and Weight Loss Treatment Targets in the USA.","authors":"Johansen, Pierre; Hunt, Barnaby; Iyer, Neeraj N; Dang-Tan, Tam; Pollock, Richard F","year":2019,"journal":"Advances in therapy, 36(5), 1190-1199","doi":"10.1007/s12325-019-00915-8","pmid":"30875029","tags":["glp-1-agonists","semaglutide"],"studyType":"Health Economics / Cost-Effectiveness Analysis","evidenceStrength":"moderate","keyFinding":"Once-weekly semaglutide (0.5 mg and 1.0 mg) offered superior cost-per-outcome versus exenatide extended-release and dulaglutide for type 2 diabetes. Semaglutide was the most effective at getting patients to all three treatment targets: HbA1c below 7.0%, HbA1c below 7.0% without hypoglycemia or weight gain, and a combined target of ≥1.0% HbA1c reduction with ≥5.0% weight loss.\n\nCritically, the cost-to-efficacy ratio also favored semaglutide — meaning it wasn't just more effective, but more cost-effective per patient who reached treatment goals. This held true for both the simple glycemic target and the more demanding composite endpoints.","whyItMatters":"GLP-1 drugs are expensive, and payers (insurance companies, employers, governments) need to know which ones deliver the best value. This analysis shows that even at US wholesale prices, semaglutide's superior efficacy makes it more cost-effective per successful outcome than older GLP-1 drugs — a finding that supports formulary inclusion and insurance coverage decisions.","specificNumbers":"Semaglutide 0.5 mg and 1.0 mg vs exenatide ER and dulaglutide · 3 endpoints assessed · superior efficacy-to-cost ratio across all endpoints · US wholesale acquisition costs (July 2018)","methodology":"Post-hoc economic analysis using efficacy data from the SUSTAIN 3 (semaglutide vs exenatide ER) and SUSTAIN 7 (semaglutide vs dulaglutide) randomized trials. Researchers calculated the proportion of patients reaching three clinical targets, then combined these with annual US treatment costs to generate cost-of-control ratios plotted on a cost-efficacy plane.","limitations":"Funded by Novo Nordisk (semaglutide manufacturer), creating potential conflict of interest. Based on wholesale acquisition costs, which don't reflect actual prices paid by patients or insurers after rebates and discounts. The analysis uses clinical trial data which may not reflect real-world effectiveness. US pricing only — results may differ in other markets. Costs from July 2018 are now outdated."},{"rthcId":"RPEP-04264","title":"Cationic cell-penetrating peptide is bactericidal against Neisseria gonorrhoeae.","authors":"John, Constance M; Li, Min; Feng, Dongxiao; Jarvis, Gary A","year":2019,"journal":"The Journal of antimicrobial chemotherapy, 74(11), 3245-3251","doi":"10.1093/jac/dkz339","pmid":"31424547","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04265","title":"Biodegradable Nanoparticles Containing Mechanism Based Peptide Inhibitors Reduce Polyglutamine Aggregation in Cell Models and Alleviate Motor Symptoms in a Drosophila Model of Huntington's Disease.","authors":"Joshi, Abhayraj S; Singh, Virender; Gahane, Avinash; Thakur, Ashwani Kumar","year":2019,"journal":"ACS chemical neuroscience, 10(3), 1603-1614","doi":"10.1021/acschemneuro.8b00545","pmid":"30452227","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04266","title":"Cationic antimicrobial peptides and periodontal physiopathology: A systematic review.","authors":"Jourdain, Marie-Laure; Velard, Frédéric; Pierrard, Loïc; Sergheraert, Johan; Gangloff, Sophie C; Braux, Julien","year":2019,"journal":"Journal of periodontal research, 54(6), 589-600","doi":"10.1111/jre.12676","pmid":"31215656","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"From 1,267 initially identified publications, 74 clinical studies met inclusion criteria. Cathelicidin (LL-37), alpha-defensins, and beta-defensins 1-3 were the most studied antimicrobial peptides in periodontal contexts. LL-37 showed significant correlations with clinical periodontal indices (probing depth, clinical attachment loss) and bacteriological indices. Results for human beta-defensins (hBDs) were inconsistent across studies due to heterogeneous methodologies, diagnostic criteria, and assay techniques. LL-37 and alpha-defensins were identified as the most promising candidates for periodontal biomarkers.","whyItMatters":"Periodontal disease affects nearly half of adults and is linked to heart disease, diabetes, and other systemic conditions. Currently, diagnosis relies on physical measurements that detect disease after it has already progressed. If antimicrobial peptides like LL-37 can serve as early biomarkers in saliva or gum fluid, they could enable earlier detection and intervention through simple, non-invasive tests.","specificNumbers":"","methodology":"Systematic review searching MEDLINE-PubMed and EMBASE databases, identifying 1,267 publications. Inclusion was limited to clinical studies measuring antimicrobial peptide expression or production in human adult oral fluids (gingival crevicular fluid or saliva) or oral tissues. Seventy-four studies met the final inclusion criteria.","limitations":"Significant heterogeneity across the 74 included studies in terms of periodontal disease definitions, assay methods, sample types, and patient populations. This prevented meta-analysis for most peptides. The inconsistent beta-defensin results highlight the need for standardized methods. Most studies were cross-sectional, limiting causal conclusions about whether peptide changes cause or result from disease."},{"rthcId":"RPEP-04267","title":"pH-Responsive PEG-Shedding and Targeting Peptide-Modified Nanoparticles for Dual-Delivery of Irinotecan and microRNA to Enhance Tumor-Specific Therapy.","authors":"Juang, Vivian; Chang, Chih-Hsien; Wang, Chen-Shen; Wang, Hsin-Ell; Lo, Yu-Li","year":2019,"journal":"Small (Weinheim an der Bergstrasse, Germany), 15(49), e1903296","doi":"10.1002/smll.201903296","pmid":"31709707","tags":["peptide-drug-delivery","cancer","nanoparticles"],"studyType":"Preclinical (In Vitro + Animal)","evidenceStrength":"Preliminary","keyFinding":"Researchers engineered smart nanoparticles decorated with three different targeting peptides — a cell-penetrating peptide, a tumor blood vessel-targeting peptide, and a mitochondria-targeting peptide — to deliver both the chemotherapy drug irinotecan and a microRNA (miR-200) that blocks cancer spread. The nanoparticles were coated with a pH-sensitive PEG layer that sheds in the acidic tumor environment, exposing the targeting peptides only where they're needed.\n\nIn lab tests on colon cancer cells, the dual-delivery system triggered cancer cell death through multiple pathways while showing low toxicity to healthy blood and intestinal cells. In mice with colorectal tumors, the nanoparticles inhibited tumor growth and reduced the systemic side effects that typically accompany irinotecan chemotherapy.","whyItMatters":"Chemotherapy drugs like irinotecan are effective cancer killers but damage healthy tissue along the way, causing debilitating side effects. Peptide-modified nanoparticles that only activate in the acidic tumor environment represent a smarter delivery approach — they protect the drug during circulation in the bloodstream and release it specifically at the tumor site. Adding miR-200 to suppress drug resistance and metastasis makes this a multi-pronged attack on cancer.","specificNumbers":"3 targeting peptides · dual cargo (irinotecan + miR-200) · pH-responsive PEG shedding · tested in HCT116 colon cancer cells · validated in CRC-bearing BALB/c mice","methodology":"The researchers designed two types of nanoparticles: liposomes carrying irinotecan and solid lipid nanoparticles carrying miR-200. Both were modified with three targeting peptides and coated with pH-sensitive PEG. They tested pH-responsive drug release, cellular uptake, and intracellular distribution in HCT116 colon cancer cells. Toxicity was assessed against blood cells and healthy intestinal cells. The combination therapy was then tested in BALB/c mice bearing colorectal tumors, monitoring tumor growth and systemic toxicity.","limitations":"This is a preclinical study using cell lines and mouse models — results may not translate directly to human colorectal cancer. The mouse model uses implanted tumors that don't fully capture the complexity of naturally occurring human CRC. Specific quantitative results (tumor reduction percentages, survival data) are not provided in the abstract. Manufacturing complexity of these multi-component nanoparticles could be a barrier to clinical translation. Long-term safety was not assessed."},{"rthcId":"RPEP-04268","title":"Use of MALDI-MS with solid-state hydrogen deuterium exchange for semi-automated assessment of peptide and protein physical stability in lyophilized solids.","authors":"Kabaria, Sneha R; Mangion, Ian; Makarov, Alexey A; Pirrone, Gregory F","year":2019,"journal":"Analytica chimica acta, 1054, 114-121","doi":"10.1016/j.aca.2018.12.034","pmid":"30712581","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04269","title":"Exendin-4 Derivatives with an Albumin-Binding Moiety Show Decreased Renal Retention and Improved GLP-1 Receptor Targeting.","authors":"Kaeppeli, Simon A M; Jodal, Andreas; Gotthardt, Martin; Schibli, Roger; Béhé, Martin","year":2019,"journal":"Molecular pharmaceutics, 16(9), 3760-3769","doi":"10.1021/acs.molpharmaceut.9b00271","pmid":"31393738","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04270","title":"Differential Roles of Each Orexin Receptor Signaling in Obesity.","authors":"Kakizaki, Miyo; Tsuneoka, Yousuke; Takase, Kenkichi; Kim, Staci J; Choi, Jinhwan; Ikkyu, Aya; Abe, Manabu; Sakimura, Kenji; Yanagisawa, Masashi; Funato, Hiromasa","year":2019,"journal":"iScience, 20, 1-13","doi":"10.1016/j.isci.2019.09.003","pmid":"31546102","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04271","title":"Cell penetrating peptides: the potent multi-cargo intracellular carriers.","authors":"Kardani, Kimia; Milani, Alireza; H Shabani, Samaneh; Bolhassani, Azam","year":2019,"journal":"Expert opinion on drug delivery, 16(11), 1227-1258","doi":"10.1080/17425247.2019.1676720","pmid":"31583914","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04272","title":"Vasopressin enhances human preemptive strike in both males and females.","authors":"Kawada, Atsushi; Nagasawa, Miho; Murata, Aiko; Mogi, Kazutaka; Watanabe, Katsumi; Kikusui, Takefumi; Kameda, Tatsuya","year":2019,"journal":"Scientific reports, 9(1), 9664","doi":"10.1038/s41598-019-45953-y","pmid":"31273244","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04273","title":"Salt-Tolerant Antifungal and Antibacterial Activities of the Corn Defensin ZmD32.","authors":"Kerenga, Bomai K; McKenna, James A; Harvey, Peta J; Quimbar, Pedro; Garcia-Ceron, Donovan; Lay, Fung T; Phan, Thanh Kha; Veneer, Prem K; Vasa, Shaily; Parisi, Kathy; Shafee, Thomas M A; van der Weerden, Nicole L; Hulett, Mark D; Craik, David J; Anderson, Marilyn A; Bleackley, Mark R","year":2019,"journal":"Frontiers in microbiology, 10, 795","doi":"10.3389/fmicb.2019.00795","pmid":"31031739","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04274","title":"In vitro Generation of Cytotoxic T Cells With Potential for Adoptive Tumor Immunotherapy of Multiple Myeloma.","authors":"Khalaf, Wafaa S; Garg, Mamta; Mohamed, Yehia S; Stover, Cordula M; Browning, Michael J","year":2019,"journal":"Frontiers in immunology, 10, 1792","doi":"10.3389/fimmu.2019.01792","pmid":"31428094","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04275","title":"CGRP, a target for preventive therapy in migraine and cluster headache: Systematic review of clinical data.","authors":"Khan, Sabrina; Olesen, Astrid; Ashina, Messoud","year":2019,"journal":"Cephalalgia : an international journal of headache, 39(3), 374-389","doi":"10.1177/0333102417741297","pmid":"29110503","tags":[],"studyType":"systematic-review","evidenceStrength":"strong","keyFinding":"All four monoclonal antibodies targeting the CGRP pathway — eptinezumab, erenumab, fremanezumab, and galcanezumab — showed positive results for preventing both episodic and chronic migraine across phase II and III clinical trials. This review of 32 eligible randomized controlled trials collectively demonstrated that blocking CGRP signaling is an effective preventive strategy for migraine.\n\nThe review noted that phase III trials were also underway for cluster headache prevention, though results were still pending at the time. The authors flagged the importance of monitoring cardiovascular effects of long-term CGRP blockade, since CGRP plays a role in blood vessel dilation and cardiovascular protection.","whyItMatters":"Before anti-CGRP antibodies, migraine prevention relied on drugs originally developed for other conditions — blood pressure medications, antidepressants, and anti-seizure drugs — none specifically designed for migraine. The CGRP pathway represented the first migraine-specific preventive target, offering a new class of treatment for the estimated 1 billion people worldwide affected by migraine. This systematic review captured a pivotal moment just as these drugs were entering clinical practice.","specificNumbers":"136 records screened · 32 eligible RCTs reviewed · 4 monoclonal antibodies evaluated · Effective in episodic and chronic migraine","methodology":"Systematic search of PubMed and ClinicalTrials.gov for randomized controlled trials investigating anti-CGRP monoclonal antibodies for migraine and cluster headache prevention. From 136 records, 32 were eligible for inclusion. The review synthesized phase II and III trial data for all four anti-CGRP antibodies.","limitations":"Published in 2019 (accepted 2017), this review captures early clinical trial data and precedes much of the post-marketing real-world evidence now available. Long-term safety data — particularly cardiovascular effects of sustained CGRP blockade — was not yet available. The cluster headache data was limited to ongoing trials without results."},{"rthcId":"RPEP-04276","title":"Combined apoptotic effects of peptide and miRNA in a peptide/miRNA nanocomplex.","authors":"Kim, Hyungjin; Kitamatsu, Mizuki; Ohtsuki, Takashi","year":2019,"journal":"Journal of bioscience and bioengineering, 128(1), 110-116","doi":"10.1016/j.jbiosc.2019.01.003","pmid":"30718146","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"TatBim peptide and miR-34a formed nanocomplexes approximately 250 nm in diameter that were efficiently internalized by cancer cells. However, increasing RNA content paradoxically reduced apoptotic activity, likely because the tightly bound complex couldn't release its components inside the cell.\n\nAttaching a photosensitizer to TatBim and applying light irradiation significantly rescued the apoptotic activity by promoting endosomal escape — allowing the peptide and RNA to disperse into the cytoplasm where they can act. Control experiments (substituting TatBim with Lipofectamine, or miR-34a with scrambled siRNA) confirmed that both the peptide and the microRNA contributed independently to the cancer cell killing effect.","whyItMatters":"Getting therapeutic RNA into cancer cells is one of the biggest challenges in gene therapy. Most delivery systems are passive carriers — they shuttle RNA inside but don't contribute to the therapeutic effect. This approach is different: the carrier peptide itself kills cancer cells, so the delivery vehicle doubles as a drug. The light-activated endosomal escape adds a layer of spatial control, potentially limiting off-target effects.","specificNumbers":"","methodology":"Researchers formed nanocomplexes by mixing TatBim peptide with miR-34a at various ratios. They characterized particle size and tested cellular uptake and apoptosis induction in HeLa cancer cells. To address the endosomal trapping problem, they conjugated a photosensitizer to TatBim and applied photoirradiation. Component-substitution experiments verified that both the peptide and RNA contributed to apoptosis independently.","limitations":"This was an in vitro study using only one cancer cell line (HeLa). No animal or human data exists. The requirement for light activation limits application to accessible tumors. The decrease in activity with higher RNA content suggests the peptide-RNA interaction needs further optimization. Scalability and stability of the nanocomplexes for clinical use were not addressed."},{"rthcId":"RPEP-04277","title":"Dual functional bioactive-peptide, AIMP1-derived peptide (AdP), for anti-aging.","authors":"Kim, Jina; Kang, Sujin; Kwon, HanJin; Moon, HoSang; Park, Min Chul","year":2019,"journal":"Journal of cosmetic dermatology, 18(1), 251-257","doi":"10.1111/jocd.12671","pmid":"29921010","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04278","title":"Human β-defensin 2 is involved in CCR2-mediated Nod2 signal transduction, leading to activation of the innate immune response in macrophages.","authors":"Kim, Ju; Yang, Ye Lin; Jang, Yong-Suk","year":2019,"journal":"Immunobiology, 224(4), 502-510","doi":"10.1016/j.imbio.2019.05.004","pmid":"31126693","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04279","title":"Targeting metastatic breast cancer with peptide epitopes derived from autocatalytic loop of Prss14/ST14 membrane serine protease and with monoclonal antibodies.","authors":"Kim, Ki Yeon; Yoon, Minsang; Cho, Youngkyung; Lee, Kwang-Hoon; Park, Sora; Lee, Se-Ra; Choi, So-Young; Lee, Deokjae; Yang, Chansik; Cho, Eun Hye; Jeon, Sangjun Davie; Kim, Seok-Hyung; Kim, Chungho; Kim, Moon Gyo","year":2019,"journal":"Journal of experimental & clinical cancer research : CR, 38(1), 363","doi":"10.1186/s13046-019-1373-y","pmid":"31426843","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04280","title":"The mitochondrial-derived peptide MOTS-c is a regulator of plasma metabolites and enhances insulin sensitivity.","authors":"Kim, Su-Jeong; Miller, Brendan; Mehta, Hemal H; Xiao, Jialin; Wan, Junxiang; Arpawong, Thalida E; Yen, Kelvin; Cohen, Pinchas","year":2019,"journal":"Physiological reports, 7(13), e14171","doi":"10.14814/phy2.14171","pmid":"31293078","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04281","title":"Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder: Two Randomized Phase 3 Trials.","authors":"Kingsberg, Sheryl A; Clayton, Anita H; Portman, David; Williams, Laura A; Krop, Julie; Jordan, Robert; Lucas, Johna; Simon, James A","year":2019,"journal":"Obstetrics and gynecology, 134(5), 899-908","doi":"10.1097/AOG.0000000000003500","pmid":"31599840","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04282","title":"Neurokinin-1 receptor-based bivalent drugs in pain management: The journey to nowhere?","authors":"Kleczkowska, Patrycja; Nowicka, Katarzyna; Bujalska-Zadrozny, Magdalena; Hermans, Emmanuel","year":2019,"journal":"Pharmacology & therapeutics, 196, 44-58","doi":"10.1016/j.pharmthera.2018.11.007","pmid":"30468743","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04283","title":"A Plant-Based Meal Increases Gastrointestinal Hormones and Satiety More Than an Energy- and Macronutrient-Matched Processed-Meat Meal in T2D, Obese, and Healthy Men: A Three-Group Randomized Crossover Study.","authors":"Klementova, Marta; Thieme, Lenka; Haluzik, Martin; Pavlovicova, Renata; Hill, Martin; Pelikanova, Terezie; Kahleova, Hana","year":2019,"journal":"Nutrients, 11(1)","doi":"10.3390/nu11010157","pmid":"30642053","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04284","title":"The Discovery and Development of Liraglutide and Semaglutide.","authors":"Knudsen, Lotte Bjerre; Lau, Jesper","year":2019,"journal":"Frontiers in endocrinology, 10, 155","doi":"10.3389/fendo.2019.00155","pmid":"30740657","tags":["glp-1-receptor-agonists","peptide-drug-development"],"studyType":"review","evidenceStrength":"n/a (review)","keyFinding":"Systematic optimization of fatty acid acylation transformed GLP-1 from a 1.5-minute half-life peptide into once-daily liraglutide (C16, 13h) and once-weekly semaglutide (C18 diacid, 165h).","whyItMatters":"Definitive account of how lipidation chemistry created the most commercially successful peptide drugs in history.","specificNumbers":"GLP-1 native: 1.5 min; liraglutide: C16, 13h half-life; semaglutide: C18 diacid, 165h half-life; 5.6x albumin affinity increase","methodology":"Historical review of drug discovery and development at Novo Nordisk.","limitations":"Industry-authored review."},{"rthcId":"RPEP-04285","title":"S-Layer Protein of Lactobacillus helveticus SBT2171 Promotes Human β-Defensin 2 Expression via TLR2-JNK Signaling.","authors":"Kobatake, Eiji; Kabuki, Toshihide","year":2019,"journal":"Frontiers in microbiology, 10, 2414","doi":"10.3389/fmicb.2019.02414","pmid":"31681252","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04286","title":"Systematic search for structural motifs of peptide binding to double-stranded DNA.","authors":"Kolchina, Nina; Khavinson, Vladimir; Linkova, Natalia; Yakimov, Alexander; Baitin, Dmitry; Afanasyeva, Arina; Petukhov, Michael","year":2019,"journal":"Nucleic acids research, 47(20), 10553-10563","doi":"10.1093/nar/gkz850","pmid":"31598715","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04287","title":"Selank, Peptide Analogue of Tuftsin, Protects Against Ethanol-Induced Memory Impairment by Regulating of BDNF Content in the Hippocampus and Prefrontal Cortex in Rats.","authors":"Kolik, L G; Nadorova, A V; Antipova, T A; Kruglov, S V; Kudrin, V S; Durnev, A D","year":2019,"journal":"Bulletin of experimental biology and medicine, 167(5), 641-644","doi":"10.1007/s10517-019-04588-9","pmid":"31625062","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Selank at 0.3 mg/kg/day for 7 days intraperitoneally produced a cognitive-stimulating effect in 9-month-old control rats (p<0.05) and prevented ethanol-induced memory and attention disturbances during alcohol withdrawal (p<0.01). In ex vivo brain tissue analysis, Selank prevented the ethanol-induced increase in BDNF content in both the hippocampus and frontal cortex (p<0.05). The protective effect on memory was assessed using the object recognition test, which measures both recognition memory and attention.","whyItMatters":"Alcohol-related cognitive impairment is a major public health problem with few effective treatments. This study suggests Selank could protect against alcohol-induced brain damage through a specific mechanism — normalizing BDNF levels. The fact that Selank also improved cognition in non-alcohol-exposed older rats suggests broader neuroprotective potential.","specificNumbers":"","methodology":"Outbred rats received 10% ethanol as their sole fluid source for 30 weeks to model chronic alcohol exposure. Selank was administered intraperitoneally at 0.3 mg/kg/day for 7 days. Memory and attention were assessed using the object recognition test. BDNF content was measured ex vivo in the hippocampus and frontal cortex. Both ethanol-exposed and control (non-exposed) 9-month-old rats were tested.","limitations":"This was an animal study in outbred rats, and results may not translate directly to humans. The sample size was not specified in the abstract. The 7-day treatment period is very short, and it's unclear if protection persists after Selank discontinuation. The ethanol-only fluid model is extreme and may not represent typical human drinking patterns. Selank is not FDA-approved and is primarily used in Russia."},{"rthcId":"RPEP-04288","title":"Casein materials show different digestion patterns using an in vitro gastrointestinal model and different release of glucagon-like peptide-1 by enteroendocrine GLUTag cells.","authors":"Komatsu, Yosuke; Wada, Yasuaki; Izumi, Hirohisa; Shimizu, Takashi; Takeda, Yasuhiro; Hira, Tohru; Hara, Hiroshi","year":2019,"journal":"Food chemistry, 277, 423-431","doi":"10.1016/j.foodchem.2018.10.123","pmid":"30502166","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Different casein processing methods produce different peptide profiles during digestion and different levels of GLP-1 release. Micellar casein concentrate (MCC) had higher digestibility and induced greater GLP-1 secretion from enteroendocrine GLUTag cells than sodium caseinate mixed with whey protein isolate (SCN + WPI). A specific peptide — GPVRGPFPIIV — was identified only in MCC digesta and confirmed to stimulate GLP-1 release when chemically synthesized and tested.","whyItMatters":"GLP-1 is the hormone targeted by blockbuster drugs like semaglutide and tirzepatide. Finding that specific food-derived peptides from milk protein can naturally stimulate GLP-1 release suggests that the way dairy products are processed could influence their metabolic benefits. Identifying the exact peptide sequence (GPVRGPFPIIV) responsible provides a molecular basis for developing functional foods or supplements that promote natural GLP-1 release.","specificNumbers":"","methodology":"Micellar casein concentrate (MCC) and sodium caseinate with whey protein isolate (SCN + WPI) were subjected to standardized in vitro gastrointestinal digestion. Digestion patterns and released peptides were characterized. GLP-1 secretion was measured using enteroendocrine GLUTag cells exposed to the digested materials. Candidate GLP-1-releasing peptides were identified from the digesta, chemically synthesized, and individually tested for GLP-1-stimulating activity.","limitations":"All experiments were in vitro — the GLP-1-releasing effects have not been confirmed in animals or humans after oral consumption. In vitro digestion may not perfectly replicate the complexity of human gastrointestinal processing. The GLUTag cell model, while standard, may not fully represent the diversity of human enteroendocrine cells. The magnitude of GLP-1 release from the identified peptide relative to pharmacological GLP-1 RAs is not reported."},{"rthcId":"RPEP-04289","title":"Protein Kinase C-delta Inhibitor Peptide Formulation using Gold Nanoparticles.","authors":"Konoeda, Hisato; Yang, Hong; Yang, Chengliang; Gower, Annette; Xu, Chun; Zhang, Wei; Liu, Mingyao","year":2019,"journal":"Journal of visualized experiments : JoVE","doi":"10.3791/58741","pmid":"30907873","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04290","title":"Intragastric Application of Aspirin, Clopidogrel, Cilostazol, and BPC 157 in Rats: Platelet Aggregation and Blood Clot.","authors":"Konosic, Sanja; Petricevic, Mate; Ivancan, Visnja; Konosic, Lucija; Goluza, Eleonora; Krtalic, Branimir; Drmic, Domagoj; Stupnisek, Mirjana; Seiwerth, Sven; Sikiric, Predrag","year":2019,"journal":"Oxidative medicine and cellular longevity, 2019, 9084643","doi":"10.1155/2019/9084643","pmid":"31976029","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BPC 157 (10 µg/kg, given orally) counteracted the inhibitory effects of aspirin, clopidogrel, and cilostazol on platelet aggregation across multiple activation pathways:\n\n- Reversed arachidonic acid-induced aggregation inhibition (vs. all three drugs)\n- Reversed arachidonic acid/PGE1 aggregation inhibition (vs. cilostazol)\n- Reversed ADP-induced aggregation inhibition (vs. clopidogrel)\n- Reversed collagen-induced aggregation inhibition (vs. clopidogrel)\n\nCritically, BPC 157 had no effect on extrinsic/intrinsic hemostasis or fibrin clot parameters (EXTEM, INTEM, FIBTEM measurements were unchanged), demonstrating specificity for platelet function rescue.","whyItMatters":"Blood-thinning drugs are essential for preventing heart attacks and strokes but increase bleeding risk. A peptide that could selectively rescue platelet function when needed — for example before emergency surgery in patients on antiplatelet therapy — would address a significant clinical gap.","specificNumbers":"","methodology":"Wistar rats received daily oral dosing of antithrombotic agents (aspirin, clopidogrel, or cilostazol at 10 mg/kg) with either BPC 157 (10 µg/kg) or saline for three days. Blood was sampled 2 hours after the last dose. Multiple electrode aggregometry measured platelet aggregation with four different agonists, and rotational thromboelastometry assessed overall clot formation parameters.","limitations":"Animal study in rats — human translation is unknown. The study comes from the primary BPC 157 research group, and independent replication is needed. The mechanism by which BPC 157 rescues platelet function is not explained. It's unclear whether this effect could dangerously counteract the therapeutic antiplatelet effects needed to prevent heart attacks. No human pharmacokinetic or safety data exists for BPC 157."},{"rthcId":"RPEP-04291","title":"Editing the immunopeptidome of melanoma cells using a potent inhibitor of endoplasmic reticulum aminopeptidase 1 (ERAP1).","authors":"Koumantou, Despoina; Barnea, Eilon; Martin-Esteban, Adrian; Maben, Zachary; Papakyriakou, Athanasios; Mpakali, Anastasia; Kokkala, Paraskevi; Pratsinis, Harris; Georgiadis, Dimitris; Stern, Lawrence J; Admon, Arie; Stratikos, Efstratios","year":2019,"journal":"Cancer immunology, immunotherapy : CII, 68(8), 1245-1261","doi":"10.1007/s00262-019-02358-0","pmid":"31222486","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Treatment of A375 melanoma cells with an ERAP1 inhibitor altered the presentation of approximately half of the 3,204 identified peptides displayed on MHC class I molecules, including about one third of peptides predicted to bind tightly to MHC-I. The inhibitor did not reduce cell-surface MHC-I expression levels.\n\nThe most surprising finding was that ERAP1 inhibition actually improved the average predicted MHC-I binding affinity of displayed peptides. This occurred because the enzyme's normal activity was destroying many high-quality potential epitopes (9–12 amino acid peptides) while allowing suboptimal long peptides to persist. Blocking ERAP1 reduced presentation of these suboptimal long peptides and increased presentation of many high-affinity shorter peptides — essentially improving the immunogenicity of the tumor cells.","whyItMatters":"Immune checkpoint inhibitors (like pembrolizumab and nivolumab) have revolutionized cancer treatment, but many patients don't respond because their tumors don't present enough recognizable peptide targets. This study introduces a fundamentally different approach: rather than boosting the immune response, manipulate what the cancer cells display on their surface to make them more immunogenic. If ERAP1 inhibitors can be developed into drugs, they could complement existing immunotherapies by making unresponsive tumors visible to the immune system.","specificNumbers":"","methodology":"Researchers treated A375 melanoma cells with a potent ERAP1 inhibitor and analyzed the presented MHC class I peptide repertoire. MHC-I molecules were isolated from treated and untreated cells, bound peptides were eluted, and identified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Peptide length distributions, binding motifs, and predicted MHC-I binding affinities were compared between treated and control conditions.","limitations":"This study was conducted entirely in cell culture using a single melanoma cell line (A375). Whether ERAP1 inhibition would enhance anti-tumor immune responses in living organisms was not tested. The peptide changes observed in vitro may differ from those occurring in the complex tumor microenvironment. The ERAP1 inhibitor's selectivity, pharmacokinetics, and potential off-target effects on normal cells (which also use ERAP1 for peptide processing) were not addressed. Whether the altered peptides would actually be recognized by patient T cells remains unknown."},{"rthcId":"RPEP-04292","title":"A small peptide antagonist of the Fas receptor inhibits neuroinflammation and prevents axon degeneration and retinal ganglion cell death in an inducible mouse model of glaucoma.","authors":"Krishnan, Anitha; Kocab, Andrew J; Zacks, David N; Marshak-Rothstein, Ann; Gregory-Ksander, Meredith","year":2019,"journal":"Journal of neuroinflammation, 16(1), 184","doi":"10.1186/s12974-019-1576-3","pmid":"31570110","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04293","title":"Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials.","authors":"Kristensen, Søren L; Rørth, Rasmus; Jhund, Pardeep S; Docherty, Kieran F; Sattar, Naveed; Preiss, David; Køber, Lars; Petrie, Mark C; McMurray, John J V","year":2019,"journal":"The lancet. Diabetes & endocrinology, 7(10), 776-785","doi":"10.1016/S2213-8587(19)30249-9","pmid":"31422062","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across seven cardiovascular outcome trials (ELIXA, LEADER, SUSTAIN-6, EXSCEL, Harmony Outcomes, REWIND, and PIONEER 6) totaling 56,004 participants, GLP-1 receptor agonists reduced major adverse cardiovascular events (MACE) by 12% (HR 0.88, 95% CI 0.82–0.94, p<0.0001).\n\nBreaking down the components: cardiovascular death was reduced by 12% (HR 0.88, p=0.003), stroke by 16% (HR 0.84, p<0.0001), and myocardial infarction by 9% (HR 0.91, p=0.043). All-cause mortality fell by 12% (HR 0.88, p=0.001), heart failure hospitalization by 9% (HR 0.91, p=0.028), and a composite kidney outcome by 17% (HR 0.83, p<0.0001), driven primarily by reduced urinary albumin excretion. No increased risk of severe hypoglycemia, pancreatitis, or pancreatic cancer was observed.","whyItMatters":"This meta-analysis provided the definitive evidence that GLP-1 receptor agonists are not just glucose-lowering drugs — they are cardiovascular and kidney-protective therapies. Published in The Lancet Diabetes & Endocrinology, it helped reshape treatment guidelines worldwide, establishing GLP-1 receptor agonists as preferred agents for type 2 diabetes patients with cardiovascular disease or high cardiovascular risk. The consistency of benefits across different drugs in the class was particularly compelling.","specificNumbers":"","methodology":"Systematic review and meta-analysis of placebo-controlled cardiovascular outcome trials of GLP-1 receptor agonists, searched via MEDLINE and Cochrane Central Register through June 2019. Seven trials met inclusion criteria. A random-effects model was used to estimate overall hazard ratios for MACE and its components, all-cause mortality, heart failure hospitalization, kidney outcomes, and safety outcomes. Subgroup analyses examined effects by cardiovascular disease history, BMI, age, baseline HbA1c, eGFR, trial duration, dosing interval, and structural homology.","limitations":"The analysis pooled trials with different GLP-1 receptor agonists, patient populations, and trial durations, which introduces heterogeneity despite the consistent results. Individual drug effects may vary. The kidney outcome was driven largely by reductions in albuminuria rather than hard endpoints like end-stage kidney disease. Most participants had established cardiovascular disease or high cardiovascular risk, so results may not apply equally to lower-risk diabetes patients. The analysis was limited to data available through June 2019."},{"rthcId":"RPEP-04294","title":"Neural modulation of social reinforcement learning by intranasal oxytocin in male adults with high-functioning autism spectrum disorder: a randomized trial.","authors":"Kruppa, Jana A; Gossen, Anna; Oberwelland Weiß, Eileen; Kohls, Gregor; Großheinrich, Nicola; Cholemkery, Hannah; Freitag, Christine M; Karges, Wolfram; Wölfle, Elke; Sinzig, Judith; Fink, Gereon R; Herpertz-Dahlmann, Beate; Konrad, Kerstin; Schulte-Rüther, Martin","year":2019,"journal":"Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 44(4), 749-756","doi":"10.1038/s41386-018-0258-7","pmid":"30390065","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04295","title":"Migraine treatment: the doors for the future are open, but with caution and prudence.","authors":"Krymchantowski, Abouch V; Krymchantowski, Ana Gabriela Ferreira; Jevoux, Carla da Cunha","year":2019,"journal":"Arquivos de neuro-psiquiatria, 77(2), 115-121","doi":"10.1590/0004-282X20190004","pmid":"30810596","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04296","title":"Safety and efficacy of targeted alpha therapy with 213Bi-DOTA-substance P in recurrent glioblastoma.","authors":"Królicki, Leszek; Bruchertseifer, Frank; Kunikowska, Jolanta; Koziara, Henryk; Królicki, Bartosz; Jakuciński, Maciej; Pawlak, Dariusz; Apostolidis, Christos; Mirzadeh, Saed; Rola, Rafał; Merlo, Adrian; Morgenstern, Alfred","year":2019,"journal":"European journal of nuclear medicine and molecular imaging, 46(3), 614-622","doi":"10.1007/s00259-018-4225-7","pmid":"30498897","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04297","title":"Immunohistological analysis of pancreatic carcinoma after vaccination with survivin 2B peptide: Analysis of an autopsy series.","authors":"Kubo, Terufumi; Tsurita, Giichiro; Hirohashi, Yoshihiko; Yasui, Hiroshi; Ota, Yasunori; Watanabe, Kazue; Murai, Aiko; Matsuo, Kazuhiko; Asanuma, Hiroko; Shima, Hiroaki; Wada, Satoshi; Nakatsugawa, Munehide; Kanaseki, Takayuki; Tsukahara, Tomohide; Mizuguchi, Toru; Hirata, Koichi; Takemasa, Ichiro; Imai, Kohzoh; Sato, Noriyuki; Torigoe, Toshihiko","year":2019,"journal":"Cancer science, 110(8), 2386-2395","doi":"10.1111/cas.14099","pmid":"31206934","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04298","title":"Alteration of peptidergic gut-brain signaling under conditions of obesity.","authors":"Kuhne, S G; Stengel, A","year":2019,"journal":"Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 70(5)","doi":"10.26402/jpp.2019.5.01","pmid":"31889037","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04299","title":"Glycoprotein D peptide-based diagnostic approach for the detection of avian infectious laryngotracheitis antibodies.","authors":"Kumar, Vishnu; Yadav, Karamchandra; Kumar, Rakesh; Chaudhary, Nitin; Kumar, Sachin","year":2019,"journal":"Avian pathology : journal of the W.V.P.A, 48(6), 602-609","doi":"10.1080/03079457.2019.1631444","pmid":"31199165","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04300","title":"Short communication: Inhibition of DNA methyltransferase and histone deacetylase increases β-defensin expression but not the effects of lipopolysaccharide or 1,25-dihydroxyvitamin D3 in bovine mammary epithelial cells.","authors":"Kweh, Mercedes F; Merriman, Kathryn E; Nelson, Corwin D","year":2019,"journal":"Journal of dairy science, 102(6), 5706-5712","doi":"10.3168/jds.2018-16141","pmid":"30954263","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04301","title":"Architecture of antimicrobial skin defense.","authors":"Kwiecien, Kamila; Zegar, Aneta; Jung, James; Brzoza, Piotr; Kwitniewski, Mateusz; Godlewska, Urszula; Grygier, Beata; Kwiecinska, Patrycja; Morytko, Agnieszka; Cichy, Joanna","year":2019,"journal":"Cytokine & growth factor reviews, 49, 70-84","doi":"10.1016/j.cytogfr.2019.08.001","pmid":"31473081","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04302","title":"The Bovine Antimicrobial Peptide Lactoferricin Interacts with Polysialic Acid without Loss of Its Antimicrobial Activity against Escherichia coli.","authors":"Kühnle, Andrea; Galuska, Christina E; Zlatina, Kristina; Galuska, Sebastian P","year":2019,"journal":"Animals : an open access journal from MDPI, 10(1)","doi":"10.3390/ani10010001","pmid":"31861263","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04303","title":"Neuropeptide Y impairs the acquisition of conditioned defeat in Syrian hamsters.","authors":"Lacey, Tiara; Sweeting, Josiah; Kingston, Rody; Smith, Michael; Markham, Chris M","year":2019,"journal":"Neuroscience letters, 690, 214-218","doi":"10.1016/j.neulet.2018.09.049","pmid":"30312751","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04304","title":"Delivery of siRNA therapeutics using cowpea chlorotic mottle virus-like particles.","authors":"Lam, Patricia; Steinmetz, Nicole F","year":2019,"journal":"Biomaterials science, 7(8), 3138-3142","doi":"10.1039/c9bm00785g","pmid":"31257379","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04305","title":"A brief report on the clinical trial on neural mobilization exercise for joint pain in patients with rheumatoid arthritis.","authors":"Lau, Yan Nok; Ng, Joseph; Lee, Shan Yee; Li, Lam Chin; Kwan, Cheuk Man; Fan, Sin Ming; Leung, Bernard Pui Lam; Lo, Chi Ngai","year":2019,"journal":"Zeitschrift fur Rheumatologie, 78(5), 474-478","doi":"10.1007/s00393-018-0521-7","pmid":"30112581","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04306","title":"Structural and functional characterization of the membrane-permeabilizing activity of Nicotiana occidentalis defensin NoD173 and protein engineering to enhance oncolysis.","authors":"Lay, Fung T; Ryan, Gemma F; Caria, Sofia; Phan, Thanh Kha; Veneer, Prem K; White, Julie A; Kvansakul, Marc; Hulett, Mark D","year":2019,"journal":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 33(5), 6470-6482","doi":"10.1096/fj.201802540R","pmid":"30794440","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04307","title":"Recent Advances in Lung Cancer Immunotherapy: Input of T-Cell Epitopes Associated With Impaired Peptide Processing.","authors":"Leclerc, Marine; Mezquita, Laura; Guillebot De Nerville, Guillaume; Tihy, Isabelle; Malenica, Ines; Chouaib, Salem; Mami-Chouaib, Fathia","year":2019,"journal":"Frontiers in immunology, 10, 1505","doi":"10.3389/fimmu.2019.01505","pmid":"31333652","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04308","title":"Fracture and Bone Mineral Density Response by Baseline Risk in Patients Treated With Abaloparatide Followed by Alendronate: Results From the Phase 3 ACTIVExtend Trial.","authors":"Leder, Benjamin Z; Zapalowski, Carol; Hu, Ming-Yi; Hattersley, Gary; Lane, Nancy E; Singer, Andrea J; Dore, Robin K","year":2019,"journal":"Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 34(12), 2213-2219","doi":"10.1002/jbmr.3848","pmid":"31411768","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04309","title":"Oral administration of transgenic biosafe microorganism containing antimicrobial peptide enhances the survival of tilapia fry infected bacterial pathogen.","authors":"Lee, Bing-Chang; Hung, Chun-Wei; Lin, Cheng-Yung; Shih, Chen-Han; Tsai, Huai-Jen","year":2019,"journal":"Fish & shellfish immunology, 95, 606-616","doi":"10.1016/j.fsi.2019.10.052","pmid":"31682999","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04310","title":"Intracellular Delivery of Nanoparticles Mediated by Lactoferricin Cell-Penetrating Peptides in an Endocytic Pathway.","authors":"Lee, Han-Jung; Huang, Yue-Wern; Aronstam, Robert S","year":2019,"journal":"Journal of nanoscience and nanotechnology, 19(2), 613-621","doi":"10.1166/jnn.2019.15751","pmid":"30360131","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The L6 cell-penetrating peptide (sequence RRWQWR) derived from bovine lactoferricin noncovalently bound to quantum dots to form stable complexes. These complexes entered human lung cancer cells most efficiently at a nitrogen/phosphate ratio of 60, using an endocytic pathway.\n\nCritically, L6 and L6/QD complexes showed no cytotoxicity, and the industrial preservative BIT did not enhance L6-mediated delivery, distinguishing its uptake mechanism from other cell-penetrating peptides.","whyItMatters":"Delivering drugs and imaging agents directly into cells remains a major challenge in medicine. Cell-penetrating peptides offer a promising solution, and showing that a milk-derived peptide can do this safely opens the door to biocompatible drug delivery systems that could improve cancer imaging and targeted therapy.","specificNumbers":"","methodology":"Researchers created complexes by mixing the L6 peptide with fluorescent quantum dot nanoparticles at various ratios. They tested delivery into human lung cancer cells and used mechanistic studies to determine the uptake pathway. Cytotoxicity was also assessed to confirm safety.","limitations":"This was an in vitro study using a single cancer cell line, so results may not translate to living organisms. The study did not test therapeutic cargo — only fluorescent quantum dots — so actual drug delivery effectiveness remains unknown. Long-term safety and biodistribution were not assessed."},{"rthcId":"RPEP-04311","title":"Orally administered collagen peptide protects against UVB-induced skin aging through the absorption of dipeptide forms, Gly-Pro and Pro-Hyp.","authors":"Lee, Hyun-Jun; Jang, Hye-Lim; Ahn, Dong-Kyu; Kim, Hun-Jung; Jeon, Hee Young; Seo, Dae Bang; Lee, Ji-Hae; Choi, Jin Kyu; Kang, Seok-Seong","year":2019,"journal":"Bioscience, biotechnology, and biochemistry, 83(6), 1146-1156","doi":"10.1080/09168451.2019.1580559","pmid":"30739561","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Fish scale collagen peptide NS (CPNS) was characterized with Gly-Pro identified as a representative bioactive dipeptide. Key findings:\n\n- In cell culture: CPNS reduced MMP-1 (collagen-degrading enzyme) production and increased type 1 procollagen synthesis in human dermal fibroblasts\n- In rats: Oral CPNS dramatically increased plasma concentrations of Gly-Pro and Pro-Hyp, confirming bioavailability\n- In 12-week hairless mouse study: Oral CPNS significantly attenuated UVB-induced wrinkle formation, reduced transepidermal water loss, decreased epidermis thickening, and increased skin hydration compared to UV-exposed controls","whyItMatters":"Collagen supplements are a multibillion-dollar industry, but the mechanism of oral collagen benefits has been debated. This study provides concrete evidence that specific dipeptides from collagen actually reach the bloodstream and that oral supplementation protects against UV-induced skin aging in a controlled animal model.","specificNumbers":"","methodology":"CPNS from fish scale was characterized by prep-HPLC and LC-MS/MS. In vitro effects were tested on human dermal fibroblasts. Oral bioavailability was confirmed by measuring plasma dipeptide levels in rats after CPNS ingestion. In vivo photoprotection was assessed in hairless mice exposed to UVB for 12 weeks while receiving oral CPNS supplementation.","limitations":"Animal study in hairless mice — UV response and skin structure differ from human skin. The UV exposure protocol was artificial and may not perfectly model real-world sun damage. Only fish scale collagen was tested; results may differ for bovine or marine collagen from other sources. No human clinical trial data was presented. Specific dosing information relative to typical human supplement doses wasn't detailed."},{"rthcId":"RPEP-04312","title":"Thymosin β-4 is a novel regulator for primary cilium formation by nephronophthisis 3 in HeLa human cervical cancer cells.","authors":"Lee, Jae-Wook; Kim, Hong Sug; Moon, Eun-Yi","year":2019,"journal":"Scientific reports, 9(1), 6849","doi":"10.1038/s41598-019-43235-1","pmid":"31048733","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04313","title":"Functional Fragments of AIMP1-Derived Peptide (AdP) and Optimized Hydrosol for Their Topical Deposition by Box-Behnken Design.","authors":"Lee, Jeong-Jun; Han, Young-Min; Kwon, Tae-Wan; Kim, Dong Hyun; Lee, Han Sol; Jung, Woo Jin; Kim, Jina; Kang, Sujin; Kim, Sang Kyum; Cho, Cheong-Weon; Lee, Keong-Ryoon; Kim, Dae-Duk; Park, Min Chul; Lee, Jae-Young","year":2019,"journal":"Molecules (Basel, Switzerland), 24(10)","doi":"10.3390/molecules24101967","pmid":"31121831","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04314","title":"Efficient Tumor Clearance and Diversified Immunity through Neoepitope Vaccines and Combinatorial Immunotherapy.","authors":"Lee, Karin L; Benz, Stephen C; Hicks, Kristin C; Nguyen, Andrew; Gameiro, Sofia R; Palena, Claudia; Sanborn, John Z; Su, Zhen; Ordentlich, Peter; Rohlin, Lars; Lee, John H; Rabizadeh, Shahrooz; Soon-Shiong, Patrick; Niazi, Kayvan; Schlom, Jeffrey; Hamilton, Duane H","year":2019,"journal":"Cancer immunology research, 7(8), 1359-1370","doi":"10.1158/2326-6066.CIR-18-0620","pmid":"31292145","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04315","title":"Evaluation of Outcomes After Initiating Triple Antidiabetic Therapy with a GLP-1 RA in an Integrated Health Care System.","authors":"Lee, Susan M; Aboubechara, Natalie; Niu, Fang; Ledesma, Vittoria Marie; Patel, Yesha A; Millares, Mirta; Hui, Rita L","year":2019,"journal":"Journal of managed care & specialty pharmacy, 25(3), 350-356","doi":"10.18553/jmcp.2019.25.3.350","pmid":"30816819","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04316","title":"Cardiovascular risk reduction with once-weekly semaglutide in subjects with type 2 diabetes: a post hoc analysis of gender, age, and baseline CV risk profile in the SUSTAIN 6 trial.","authors":"Leiter, Lawrence A; Bain, Stephen C; Hramiak, Irene; Jódar, Esteban; Madsbad, Sten; Gondolf, Theis; Hansen, Thomas; Holst, Ingrid; Lingvay, Ildiko","year":2019,"journal":"Cardiovascular diabetology, 18(1), 73","doi":"10.1186/s12933-019-0871-8","pmid":"31167654","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04317","title":"Novel Biology of Tachykinins in Gonadotropin-Releasing Hormone Secretion.","authors":"Leon, Silvia; Navarro, Víctor M","year":2019,"journal":"Seminars in reproductive medicine, 37(3), 109-118","doi":"10.1055/s-0039-3400252","pmid":"31869838","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tachykinins (NKA, NKB, and substance P) participate in the central control of GnRH release through neuronal circuits that activate Kiss1 neurons and synchronize their activity within the arcuate nucleus. Their roles extend across the full spectrum of reproductive function: regulating the pulsatile pattern of GnRH release, determining the timing of puberty onset, and controlling the preovulatory LH surge in females. The review synthesizes evidence that tachykinins are critical for all major aspects of fertility attainment and maintenance.","whyItMatters":"Understanding how tachykinins regulate fertility opens doors for new treatments for reproductive disorders. Neurokinin B is already a drug target — NK3 receptor antagonists are being developed for conditions like polycystic ovary syndrome and endometriosis. Deeper knowledge of the full tachykinin system could yield additional therapeutic opportunities.","specificNumbers":"","methodology":"This is a narrative review article summarizing recent advances in understanding tachykinin biology in reproductive neuroendocrinology, drawing from both animal studies and human data.","limitations":"As a review article, this paper synthesizes existing research rather than presenting new data. The authors note existing controversies and open questions in the field, including unresolved aspects of how individual tachykinins interact within the reproductive circuits."},{"rthcId":"RPEP-04318","title":"Increased pain and inflammatory sensitivity in growth hormone-releasing hormone (GHRH) knockout mice.","authors":"Leone, Sheila; Chiavaroli, Annalisa; Recinella, Lucia; Orlando, Giustino; Ferrante, Claudio; Marconi, Guya Diletta; Gasparo, Irene; Bitto, Alessandra; Salvatori, Roberto; Brunetti, Luigi","year":2019,"journal":"Prostaglandins & other lipid mediators, 144, 106362","doi":"10.1016/j.prostaglandins.2019.106362","pmid":"31301405","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Mice lacking the growth hormone-releasing hormone (GHRH) gene showed increased sensitivity to both pain and inflammation compared to normal mice. GHRH knockout mice had decreased response latency on the hot plate test (faster pain response), increased licking/biting during the formalin test (especially in the inflammatory phase), and significantly greater colonic inflammation after DSS treatment. Inflammatory markers — PGE2, 8-iso-PGF2α, COX-2, and TNF-α — were all elevated more dramatically in knockout mice, both in vivo and ex vivo.","whyItMatters":"GHRH is primarily known for stimulating growth hormone release, but this study reveals it also plays a protective role against pain and inflammation. This finding has implications for understanding why people with growth hormone deficiency often experience increased pain sensitivity and inflammatory conditions, and it opens potential new therapeutic avenues where GHRH or its analogs could be used for anti-inflammatory or analgesic purposes beyond their traditional endocrine applications.","specificNumbers":"","methodology":"GHRH knockout (-/-) mice were compared to wild-type (+/+) controls across multiple pain and inflammation models: hot plate test for acute nociception, formalin test for acute and persistent inflammatory pain, and dextran sodium sulfate (DSS)-induced colitis for chronic intestinal inflammation. Ex vivo colon segments were incubated with LPS to assess inflammatory response. Outcome measures included behavioral responses, macroscopic and histological examination, PGE2 and 8-iso-PGF2α levels, and COX-2 and TNF-α gene expression.","limitations":"This is a preclinical mouse study using constitutive gene knockout, meaning GHRH was absent throughout development — not just acutely suppressed. Developmental effects may confound the interpretation. Results were obtained only in male mice, limiting generalizability. The study demonstrates correlation between GHRH absence and increased pain/inflammation but cannot distinguish direct GHRH effects from secondary consequences of growth hormone deficiency. Specific numerical data (effect sizes, p-values) for behavioral tests are not detailed in the abstract."},{"rthcId":"RPEP-04319","title":"Substance P-mediated cardiac mast cell activation: An in vitro study.","authors":"Levick, Scott P; Brower, Gregory L; Janicki, Joseph S","year":2019,"journal":"Neuropeptides, 74, 52-59","doi":"10.1016/j.npep.2019.01.002","pmid":"30660328","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04320","title":"Hydrolysed Collagen from Sheepskins as a Source of Functional Peptides with Antioxidant Activity.","authors":"León-López, Arely; Fuentes-Jiménez, Lucía; Hernández-Fuentes, Alma Delia; Campos-Montiel, Rafael G; Aguirre-Álvarez, Gabriel","year":2019,"journal":"International journal of molecular sciences, 20(16)","doi":"10.3390/ijms20163931","pmid":"31412541","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04321","title":"A Proresolving Peptide Nanotherapy for Site-Specific Treatment of Inflammatory Bowel Disease by Regulating Proinflammatory Microenvironment and Gut Microbiota.","authors":"Li, Chenwen; Zhao, Yang; Cheng, Juan; Guo, Jiawei; Zhang, Qixiong; Zhang, Xiangjun; Ren, Jiong; Wang, Fengchao; Huang, Jun; Hu, Houyuan; Wang, Ruibing; Zhang, Jianxiang","year":2019,"journal":"Advanced science (Weinheim, Baden-Wurttemberg, Germany), 6(18), 1900610","doi":"10.1002/advs.201900610","pmid":"31559126","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The oxidation-responsive nanoparticles (AON) containing the annexin A1-mimetic peptide Ac2-26 achieved site-specific drug release at inflamed colon tissue by responding to elevated reactive oxygen species (ROS) levels. The nanoparticle shell protected the peptide from degradation in the harsh gastrointestinal environment.\n\nMechanistically, AON decreased expression of proinflammatory mediators, reduced inflammatory cell infiltration, promoted the cleanup of dying neutrophils (efferocytosis), and shifted macrophages toward an anti-inflammatory state. Therapeutically, this translated to reduced inflammation symptoms, accelerated intestinal mucosal wound healing, reshaped gut microbiota composition, and increased short-chain fatty acid production. Oral delivery showed an excellent safety profile.","whyItMatters":"IBD affects millions worldwide and current treatments often have significant side effects or lose effectiveness over time. This approach is innovative because it combines a naturally-inspired anti-inflammatory peptide with smart delivery technology that activates only at disease sites, potentially reducing side effects. The strategy of accelerating inflammation resolution rather than simply suppressing immunity represents a fundamentally different treatment philosophy.","specificNumbers":"","methodology":"Researchers engineered oxidation-responsive nanoparticles loaded with the proresolving peptide Ac2-26 (an annexin A1-mimetic). These nanoparticles were designed to break down and release their peptide payload in the presence of high ROS concentrations found at inflamed sites. The therapy was administered orally to mice with induced inflammatory bowel disease, and the team assessed inflammation markers, tissue healing, immune cell behavior, gut microbiota changes, and safety outcomes.","limitations":"This was a preclinical study in mice, and IBD in animal models does not fully replicate human disease. Specific quantitative outcomes (percent improvement, statistical comparisons) were not detailed in the abstract. Long-term efficacy and safety beyond the study period were not assessed. Manufacturing scalability and cost of the nanoparticle system were not addressed."},{"rthcId":"RPEP-04322","title":"Synergistically enhanced anticancer effect of codelivered curcumin and siPlk1 by stimuli-responsive α-lactalbumin nanospheres.","authors":"Li, Dan; Shi, Mengxuan; Bao, Cheng; Bao, Weier; Zhang, Liwei; Jiao, Lulu; Li, Tao; Li, Yuan","year":2019,"journal":"Nanomedicine (London, England), 14(5), 595-612","doi":"10.2217/nnm-2018-0291","pmid":"30806584","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04323","title":"Inflammatory and fibrosis infiltration in synovium associated with the progression in developmental dysplasia of the hip.","authors":"Li, De; Wang, Hui; He, Ji-Ye; Wang, Cheng-Long; Feng, Wei-Jia; Shen, Chao; Zhu, Jun-Feng; Wang, Dong-Liang; Chen, Xiao-Dong","year":2019,"journal":"Molecular medicine reports, 19(4), 2808-2816","doi":"10.3892/mmr.2019.9910","pmid":"30720141","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04324","title":"Thymosin beta 4 attenuates oxidative stress-induced injury of spinal cord-derived neural stem/progenitor cells through the TLR4/MyD88 pathway.","authors":"Li, Hongwei; Wang, Yonggang; Hu, Xuchang; Ma, Bing; Zhang, Haihong","year":2019,"journal":"Gene, 707, 136-142","doi":"10.1016/j.gene.2019.04.083","pmid":"31054361","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Thymosin β4 dose-dependently increased the viability of neural stem/progenitor cells (NSPCs) exposed to hydrogen peroxide-induced oxidative stress. The peptide reversed multiple markers of injury: it normalized intracellular calcium concentrations, reduced lactate dehydrogenase release (a marker of cell damage), decreased apoptosis (programmed cell death), lowered reactive oxygen species (ROS) production, and reduced pro-inflammatory cytokine levels.\n\nThe mechanism was identified as suppression of the TLR4/MyD88 signaling pathway. Thymosin β4 reduced expression of both TLR4 and MyD88 in stressed cells, and a specific TLR4/MyD88 pathway inhibitor replicated all of thymosin β4's protective effects — confirming this pathway as the key mediator of the peptide's neuroprotective action.","whyItMatters":"Spinal cord injuries are devastating and largely irreparable with current medicine. Stem cell transplantation is a promising approach, but the chemical environment at the injury site kills most transplanted cells before they can do their job. Finding ways to protect these cells — as thymosin β4 appears to do — could dramatically improve the success of stem cell therapies for spinal cord injury patients.","specificNumbers":"","methodology":"Researchers isolated neural stem/progenitor cells from rat spinal cords and exposed them to hydrogen peroxide (H2O2) to simulate the oxidative stress environment after spinal cord injury. They measured cell viability using MTT assay, assessed calcium concentrations and lactate dehydrogenase release, quantified apoptosis, measured ROS production and inflammatory cytokine levels, and examined TLR4 and MyD88 expression. A TLR4/MyD88 pathway inhibitor was used to confirm the mechanism.","limitations":"This was an in vitro study using isolated rat neural stem cells exposed to hydrogen peroxide, which is a simplified model of the complex secondary injury environment in real spinal cord injuries. The study did not test whether thymosin β4 improves stem cell survival or functional recovery in living animals. Dosing and delivery strategies for clinical translation were not addressed."},{"rthcId":"RPEP-04325","title":"Antifungal Potency and Modes of Action of a Novel Olive Tree Defensin Against Closely Related Ascomycete Fungal Pathogens.","authors":"Li, Hui; Velivelli, Siva L S; Shah, Dilip M","year":2019,"journal":"Molecular plant-microbe interactions : MPMI, 32(12), 1649-1664","doi":"10.1094/MPMI-08-19-0224-R","pmid":"31425003","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04326","title":"Targeted and MMP-2/9 responsive peptides for the treatment of rheumatoid arthritis.","authors":"Li, Na; Qiao, Yonghui; Xue, Lingping; Xu, Shiqi; Zhang, Nan","year":2019,"journal":"International journal of pharmaceutics, 569, 118625","doi":"10.1016/j.ijpharm.2019.118625","pmid":"31425817","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The engineered RMTQ peptide demonstrated enhanced cytoplasmic delivery, greater reduction of pro-inflammatory factors, and better efficacy than the unmodified QAW peptide in adjuvant-induced arthritis mice. RMTQ's anti-inflammatory efficacy matched dexamethasone (DEX), the standard steroid treatment, while showing a superior safety profile.\n\nThe modular design incorporated four functional elements: QAW (the anti-inflammatory tripeptide), a cell-penetrating peptide for intracellular delivery, an MMP-2/9-cleavable linker for inflammation-responsive activation, and an RGD targeting peptide for inflammation site homing.","whyItMatters":"Rheumatoid arthritis treatments face a trade-off between efficacy and side effects — steroids work well but cause bone loss, weight gain, and immune suppression with long-term use. A peptide therapeutic matching steroid efficacy with better safety could transform RA management. The smart targeting design means the drug activates primarily at inflammation sites, reducing systemic exposure.","specificNumbers":"","methodology":"The study used adjuvant-induced arthritis (AIA) mouse models. The RMTQ peptide was engineered by combining the anti-inflammatory QAW tripeptide with a cell-penetrating peptide, an MMP-2/9 digestive peptide linker, and an RGD inflammation-targeting peptide. In vitro testing assessed cellular uptake and pro-inflammatory factor reduction. In vivo efficacy was compared to unmodified QAW and dexamethasone in AIA mice.","limitations":"The study was conducted in mice with adjuvant-induced arthritis, which may not fully replicate human rheumatoid arthritis. Specific quantitative data on efficacy endpoints and safety parameters are not detailed in the abstract. Long-term safety, pharmacokinetics, and immunogenicity of the engineered peptide were not assessed. The scalability of manufacturing this multi-component peptide for clinical use is not addressed."},{"rthcId":"RPEP-04327","title":"Tachykinin NK1 receptor antagonist L-733,060 and substance P deletion exert neuroprotection through inhibiting oxidative stress and cell death after traumatic brain injury in mice.","authors":"Li, Qianqian; Wu, Xiao; Yang, Yanyan; Zhang, Yue; He, Fang; Xu, Xiang; Zhang, Ziwei; Tao, Luyang; Luo, Chengliang","year":2019,"journal":"The international journal of biochemistry & cell biology, 107, 154-165","doi":"10.1016/j.biocel.2018.12.018","pmid":"30593954","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Both pharmacological blockade of substance P's receptor (NK1R antagonist L-733,060) and genetic deletion of substance P provided significant neuroprotection after traumatic brain injury in mice. Both approaches reduced motor and memory deficits, lesion volume, brain swelling, and blood-brain barrier disruption. The protective mechanisms involved inhibition of mitochondrial cytochrome c release, caspase-3 activation (cell death), oxidative stress, and neuroinflammation. TBI increased substance P levels in serum and cortex and upregulated NK1R expression, with NK1R upregulation occurring independent of substance P levels.","whyItMatters":"Traumatic brain injury affects millions yearly with no approved neuroprotective drug treatments. This study identifies substance P — a well-characterized neuropeptide — as a therapeutic target for TBI. Since NK1R antagonists (substance P receptor blockers) already exist as approved drugs for other conditions (like aprepitant for nausea), repurposing them for TBI could accelerate clinical translation.","specificNumbers":"Wild type + SP knockout mice · controlled cortical impact model · reduced motor deficits · reduced spatial memory deficits · reduced lesion volume · reduced brain water content · reduced BBB disruption · inhibited caspase-3 · reduced ROS production","methodology":"Adult male C57BL/6J wild-type mice and substance P knockout (SPKO) mice received controlled cortical impact TBI. Wild-type mice were treated with NK1R antagonist L-733,060 or vehicle. Outcomes included motor function, spatial memory, lesion volume, brain water content, blood-brain barrier permeability, and molecular markers of cell death (cytochrome c, caspase-3), oxidative stress, and neuroinflammation. In vitro scratch injury models complemented the in vivo findings.","limitations":"This is a preclinical mouse study, and TBI in mice may not fully recapitulate human brain injury pathology. The controlled cortical impact model represents only one type of TBI. Long-term functional outcomes beyond the acute phase were not reported. The optimal therapeutic window for NK1R antagonist administration after TBI was not established. The drug L-733,060 is a research compound, not a clinically available NK1R antagonist."},{"rthcId":"RPEP-04328","title":"Self-Assembled Nanofibers Elicit Potent HPV16 E7-Specific Cellular Immunity And Abolish Established TC-1 Graft Tumor.","authors":"Li, Sijin; Zhang, Qishu; Bai, Hongmei; Huang, Weiwei; Shu, Congyan; Ye, Chao; Sun, Wenjia; Ma, Yanbing","year":2019,"journal":"International journal of nanomedicine, 14, 8209-8219","doi":"10.2147/IJN.S214525","pmid":"31632028","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The HPV16 E7 peptide (residues 44-62) was attached to the self-assembling peptide Q11 to create nanofibers used in two vaccination strategies:\n\nPreventive: Nanofiber immunization almost completely suppressed TC-1 tumor growth and even prevented tumor re-establishment after a 6-week rest period\n\nTherapeutic:\n- 66.7% tumor-free rate in mice with 2-3 mm established tumors\n- 50% tumor-free rate in mice with larger 5-6 mm tumors\n- Significantly increased effector Th1 cells, cytotoxic T lymphocytes (CTLs), IFN-γ, and TNF-α\n- Reduced Th2 cells, myeloid-derived suppressor cells (MDSCs), and IL-4 compared to controls\n- Nanofibers outperformed unassembled peptides for treating larger established tumors","whyItMatters":"Existing HPV vaccines (Gardasil, Cervarix) prevent infection but cannot treat existing HPV cancers. Therapeutic HPV vaccines have shown disappointing clinical results, largely because they fail to generate strong enough T-cell responses to overcome the tumor's immune-suppressive environment. This nanofiber approach addresses both problems: the self-assembling structure naturally enhances immune activation (no separate adjuvant needed), and the resulting immune response is strong enough to eliminate established tumors in a significant fraction of animals.","specificNumbers":"","methodology":"HPV16 E744-62 peptide was chemically conjugated to the N-terminus of the self-assembling peptide Q11. The conjugates formed nanofibers and were used to immunize C57BL/6 mice in a TC-1 tumor graft model. Two strategies were tested: preventive (immunization before tumor challenge) and therapeutic (immunization after tumors were established at 2-3 mm or 5-6 mm). Immune responses were evaluated by measuring Th1/Th2 cells, CTLs, MDSCs, IFN-γ, TNF-α, and IL-4 in E7 peptide-stimulated splenocytes. Tumor growth and tumor-free survival were tracked.","limitations":"This is a mouse study using a transplanted tumor model (TC-1), which does not fully replicate human HPV-related cancers that develop over years within an immunosuppressive microenvironment. The TC-1 model is relatively immunogenic, which may overestimate vaccine efficacy. Sample sizes per group are not specified in the abstract. No human safety or efficacy data exist. The long-term durability of the immune response is only partially addressed (6-week re-challenge). Manufacturing and stability challenges for nanofiber vaccines are not discussed."},{"rthcId":"RPEP-04329","title":"M10 peptide attenuates silica-induced pulmonary fibrosis by inhibiting Smad2 phosphorylation.","authors":"Li, Yan; Ji, Xiaoming; Yao, Wenxi; Pan, Honghong; Li, Ping; Liu, Yi; Yuan, Jiali; Xu, Qi; Ni, Chunhui","year":2019,"journal":"Toxicology and applied pharmacology, 376, 46-57","doi":"10.1016/j.taap.2019.05.015","pmid":"31125577","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04330","title":"miR-200a mediates protection of thymosin β-4 in cardiac microvascular endothelial cells as a novel mechanism under hypoxia-reoxygenation injury.","authors":"Li, Yang; Zhu, Xiaolong; Liu, Xiping; Du, Aolin; Yu, Bo","year":2019,"journal":"Journal of cellular biochemistry, 120(11), 19098-19106","doi":"10.1002/jcb.29237","pmid":"31265170","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04331","title":"Tranexamic acid ameliorates rosacea symptoms through regulating immune response and angiogenesis.","authors":"Li, Yangfan; Xie, Hongfu; Deng, Zhili; Wang, Ben; Tang, Yan; Zhao, Zhixiang; Yuan, Xin; Zuo, Zhihong; Xu, San; Zhang, Yiya; Li, Ji","year":2019,"journal":"International immunopharmacology, 67, 326-334","doi":"10.1016/j.intimp.2018.12.031","pmid":"30578968","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04332","title":"Peptides with therapeutic potential in the venom of the scorpion Buthus martensii Karsch.","authors":"Li, Zhongjie; Hu, Ping; Wu, Wenlan; Wang, Yong","year":2019,"journal":"Peptides, 115, 43-50","doi":"10.1016/j.peptides.2019.02.009","pmid":"30858089","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04333","title":"Combined transcriptomic and proteomic analysis reveals a diversity of venom-related and toxin-like peptides expressed in the mat anemone Zoanthus natalensis (Cnidaria, Hexacorallia).","authors":"Liao, Qiwen; Gong, Guiyi; Poon, Terence C W; Ang, Irene L; Lei, Kate M K; Siu, Shirley Weng In; Wong, Clarence Tsun Ting; Rádis-Baptista, Gandhi; Lee, Simon Ming-Yuen","year":2019,"journal":"Archives of toxicology, 93(6), 1745-1767","doi":"10.1007/s00204-019-02456-z","pmid":"31203412","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04334","title":"Combined Amylin/GLP-1 pharmacotherapy to promote and sustain long-lasting weight loss.","authors":"Liberini, Claudia G; Koch-Laskowski, Kieran; Shaulson, Evan; McGrath, Lauren E; Lipsky, Rachele K; Lhamo, Rinzin; Ghidewon, Misgana; Ling, Tyler; Stein, Lauren M; Hayes, Matthew R","year":2019,"journal":"Scientific reports, 9(1), 8447","doi":"10.1038/s41598-019-44591-8","pmid":"31186439","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04335","title":"Poly-arginine-18 peptides do not exacerbate bleeding, or improve functional outcomes following collagenase-induced intracerebral hemorrhage in the rat.","authors":"Liddle, Lane; Reinders, Ryan; South, Samantha; Blacker, David; Knuckey, Neville; Colbourne, Frederick; Meloni, Bruno","year":2019,"journal":"PloS one, 14(11), e0224870","doi":"10.1371/journal.pone.0224870","pmid":"31697775","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04336","title":"Retinoids Enhance the Expression of Cathelicidin Antimicrobial Peptide during Reactive Dermal Adipogenesis.","authors":"Liggins, Marc C; Li, Fengwu; Zhang, Ling-Juan; Dokoshi, Tatsuya; Gallo, Richard L","year":2019,"journal":"Journal of immunology (Baltimore, Md. : 1950), 203(6), 1589-1597","doi":"10.4049/jimmunol.1900520","pmid":"31420464","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04337","title":"Graphene oxide containing self-assembling peptide hybrid hydrogels as a potential 3D injectable cell delivery platform for intervertebral disc repair applications.","authors":"Ligorio, Cosimo; Zhou, Mi; Wychowaniec, Jacek K; Zhu, Xinyi; Bartlam, Cian; Miller, Aline F; Vijayaraghavan, Aravind; Hoyland, Judith A; Saiani, Alberto","year":2019,"journal":"Acta biomaterialia, 92, 92-103","doi":"10.1016/j.actbio.2019.05.004","pmid":"31091473","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A hybrid hydrogel combining the self-assembling peptide FEFKFEFK with graphene oxide (GO) nanoflakes achieved mechanical properties matching the nucleus pulposus (the gel-like core of spinal discs). The peptide coated GO flakes and formed short fibrils on their surface through strong molecular interactions. The GO-F820 hybrid hydrogel maintained high cell viability and metabolic activity of nucleus pulposus cells in 3D culture over 7 days. The hydrogel is injectable, making it suitable for minimally invasive delivery to degenerating discs.","whyItMatters":"Lower back pain from disc degeneration affects millions of people, and current treatments (surgery, steroid injections, pain management) don't repair the underlying tissue. Injecting healthy cells into the damaged disc could regenerate it, but the cells need a scaffold to survive and stay in place. This study shows that a peptide-based injectable hydrogel reinforced with graphene oxide can match the mechanical properties of natural disc tissue and keep cells alive — a key step toward a cell-based disc repair therapy.","specificNumbers":"FEFKFEFK peptide + graphene oxide · Mechanical properties match nucleus pulposus · High cell viability over 7 days · Injectable 3D scaffold · pH-dependent properties (pH 4 vs. pH 7)","methodology":"Self-assembling peptide (FEFKFEFK) hydrogels were combined with graphene oxide nanoflakes at various concentrations. Peptide-GO interactions were characterized by multiple techniques. Mechanical properties were measured at pH 4 and pH 7 (after conditioning with cell culture media). Bovine nucleus pulposus cells were cultured within the hydrogel in 3D for 7 days, with cell viability and metabolic activity assessed.","limitations":"This is an in vitro study using bovine (cow) disc cells, not human cells. The 7-day culture period is too short to assess long-term cell behavior, tissue regeneration, or matrix production. No in vivo injection into actual disc tissue was performed. The mechanical match to natural NP tissue was demonstrated but whether the hydrogel maintains its properties under the dynamic loading conditions of a living spine is unknown."},{"rthcId":"RPEP-04338","title":"Graphene oxide containing self-assembling peptide hybrid hydrogels as a potential 3D injectable cell delivery platform for intervertebral disc repair applications.","authors":"Ligorio, Cosimo; Zhou, Mi; Wychowaniec, Jacek K; Zhu, Xinyi; Bartlam, Cian; Miller, Aline F; Vijayaraghavan, Aravind; Hoyland, Judith A; Saiani, Alberto","year":2019,"journal":"Acta biomaterialia, 92, 92-103","doi":"10.1016/j.actbio.2019.05.004","pmid":"31091473","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04339","title":"How Satiating Are the 'Satiety' Peptides: A Problem of Pharmacology versus Physiology in the Development of Novel Foods for Regulation of Food Intake.","authors":"Lim, Jia Jiet; Poppitt, Sally D","year":2019,"journal":"Nutrients, 11(7)","doi":"10.3390/nu11071517","pmid":"31277416","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04340","title":"Peptides of tetraspanin oncoprotein CD151 trigger active immunity against primary tumour and experimental lung metastasis.","authors":"Lin, Wanzun; Liu, Jun; Chen, Juhui; Li, Jiancheng; Qiu, Sufang; Ma, Jiayu; Lin, Xiandong; Zhang, Lurong; Wu, Junxin","year":2019,"journal":"EBioMedicine, 49, 133-144","doi":"10.1016/j.ebiom.2019.10.025","pmid":"31668880","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Peptides derived from the oncoprotein CD151 triggered active anti-tumor immunity in two mouse cancer models — H22 hepatoma (primary liver cancer) and 4T1 breast cancer lung metastases. The peptide vaccines activated CD8+IFNγ+ killer T cells and suppressed myeloid-derived suppressor cells (MDSCs), a key immunosuppressive population in tumors. Mice immunized with CD151 peptides showed prolonged survival in the lung metastasis model. CD151 was identified as an ideal tumor-associated antigen through proteomic analysis of radiation-stressed tumor cells.","whyItMatters":"Unlike personalized neoantigen vaccines that must be custom-designed for each patient, CD151 is an oncoprotein that is broadly overexpressed across many cancer types — making it a potential off-the-shelf vaccine target. The approach of identifying antigens that become upregulated under radiation stress could reveal other promising targets. The dual mechanism — activating killer T cells while suppressing immunosuppressive cells — addresses two major hurdles in cancer immunotherapy.","specificNumbers":"2 mouse cancer models (H22 hepatoma, 4T1 breast metastasis) · CD8+IFNγ+ T cell activation · MDSC suppression · Prolonged survival in metastasis model · 8 Gy irradiation for antigen discovery","methodology":"Proteomic and bioinformatic analyses of 8 Gy-irradiated tumor cells identified CD151 as a tumor-associated antigen. Peptides were designed based on MHC-I binding predictions and immunogenicity analysis, then synthesized. Efficacy was tested in H22 hepatoma and 4T1 breast cancer lung metastasis mouse models using cytotoxicity assays, flow cytometry, immunohistochemistry, in vivo bioluminescence imaging, and survival analysis.","limitations":"This is a preclinical mouse study using two tumor models. Human CD151 expression patterns and immunogenicity may differ. The long-term durability of the immune response was not characterized. Whether CD151 peptide vaccines would be effective against established, bulky tumors (rather than early-stage or metastatic seeding) is unclear. Safety regarding potential autoimmunity against normal CD151-expressing tissues was not deeply explored."},{"rthcId":"RPEP-04341","title":"Hypothalamic Reproductive Endocrine Pulse Generator Activity Independent of Neurokinin B and Dynorphin Signaling.","authors":"Lippincott, Margaret F; León, Silvia; Chan, Yee-Ming; Fergani, Chrysanthi; Talbi, Rajae; Farooqi, I Sadaf; Jones, Christopher M; Arlt, Wiebke; Stewart, Susan E; Cole, Trevor R; Terasawa, Ei; Hall, Janet E; Shaw, Natalie D; Navarro, Victor M; Seminara, Stephanie Beth","year":2019,"journal":"The Journal of clinical endocrinology and metabolism, 104(10), 4304-4318","doi":"10.1210/jc.2019-00146","pmid":"31132118","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In both humans and mice completely lacking neurokinin B:\n\n- LH pulses were preserved but at reduced frequency (slow pulse rate)\n- Opioid antagonism (blocking dynorphin with naloxone) increased LH pulse frequency\n- Exogenous kisspeptin stimulated LH responses normally\n- GnRH administration triggered normal pituitary responses\n\nThis demonstrates that:\n1. Neither NKB nor dynorphin is required for GnRH pulse generation\n2. Both peptides modulate pulse frequency in opposing directions (NKB accelerates, dynorphin decelerates)\n3. Kisspeptin responsiveness is maintained regardless of NKB status\n4. The fundamental pulse-generating mechanism exists independently of NKB/dynorphin signaling","whyItMatters":"This study fundamentally refines the KNDy neuron model — the prevailing theory of how the brain controls reproduction. By showing that the GnRH pulse generator works without NKB, it repositions NKB and dynorphin as frequency modulators rather than essential generators. This has direct implications for drug development: drugs targeting NKB or dynorphin receptors will modulate but not abolish reproductive function, which is important for predicting therapeutic effects and side effects.","specificNumbers":"","methodology":"Case-control study combining human and mouse genetics. Researchers studied members of a consanguineous family carrying biallelic loss-of-function mutations in the NKB gene, using frequent blood sampling to characterize LH pulse patterns. Kisspeptin, GnRH, and naloxone (opioid antagonist) were administered to probe system function. NKB-knockout mice were subjected to identical pharmacological tests for cross-species validation.","limitations":"The human data comes from a single consanguineous family, limiting generalizability. The rare genetic condition provides a unique natural experiment but with very small sample sizes. Compensatory mechanisms during development may have partially offset NKB loss. Naloxone is a non-specific opioid antagonist (not selective for dynorphin's κ-opioid receptor), so effects could involve other opioid pathways. The study doesn't identify what the fundamental pulse-generating mechanism is — only that it doesn't require NKB."},{"rthcId":"RPEP-04342","title":"Permeability of Cyclic Peptide Macrocycles and Cyclotides and Their Potential as Therapeutics.","authors":"Liras, Spiros; Mcclure, Kim F","year":2019,"journal":"ACS medicinal chemistry letters, 10(7), 1026-1032","doi":"10.1021/acsmedchemlett.9b00149","pmid":"31312403","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04343","title":"Phosphorylation of extracellular signal-regulated kinase 1/2 in subepidermal nerve fibers mediates hyperalgesia following diabetic peripheral neuropathy.","authors":"Liu, Chiung-Hui; Lan, Chyn-Tair; Chen, Li-You; Liao, Wen-Chieh; Ko, Miau-Hwa; Tseng, To-Jung","year":2019,"journal":"Neurotoxicology, 71, 60-74","doi":"10.1016/j.neuro.2018.12.006","pmid":"30583000","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04344","title":"Self-assembly of mitochondria-specific peptide amphiphiles amplifying lung cancer cell death through targeting the VDAC1-hexokinase-II complex.","authors":"Liu, Dan; Angelova, Angelina; Liu, Jianwen; Garamus, Vasil M; Angelov, Borislav; Zhang, Xinlei; Li, Yawen; Feger, Guillaume; Li, Na; Zou, Aihua","year":2019,"journal":"Journal of materials chemistry. B, 7(30), 4706-4716","doi":"10.1039/c9tb00629j","pmid":"31364685","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04345","title":"Enhanced efficiency of mitochondria-targeted peptide SS-31 for acute kidney injury by pH-responsive and AKI-kidney targeted nanopolyplexes.","authors":"Liu, Di; Jin, Feiyang; Shu, Gaofeng; Xu, Xiaoling; Qi, Jing; Kang, Xuqi; Yu, Hui; Lu, Kongjun; Jiang, Saiping; Han, Feng; You, Jian; Du, Yongzhong; Ji, Jiansong","year":2019,"journal":"Biomaterials, 211, 57-67","doi":"10.1016/j.biomaterials.2019.04.034","pmid":"31085359","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04346","title":"Hexapeptide-conjugated calcitonin for targeted therapy of osteoporosis.","authors":"Liu, Yanpeng; Yu, Peng; Peng, Xu; Huang, Qin; Ding, Mingming; Chen, Yantao; Jin, Ruitao; Xie, Jing; Zhao, Changsheng; Li, Jianshu","year":2019,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 304, 39-50","doi":"10.1016/j.jconrel.2019.04.042","pmid":"31054990","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04347","title":"Risk of Malignant Neoplasia with Glucagon-Like Peptide-1 Receptor Agonist Treatment in Patients with Type 2 Diabetes: A Meta-Analysis.","authors":"Liu, Yufang; Zhang, Xiaomei; Chai, Sanbao; Zhao, Xin; Ji, Linong","year":2019,"journal":"Journal of diabetes research, 2019, 1534365","doi":"10.1155/2019/1534365","pmid":"31396537","tags":["GLP-1-agonists","cancer-risk"],"studyType":"meta-analysis","evidenceStrength":"high","keyFinding":"A meta-analysis of 34 randomized controlled trials involving 50,452 patients with type 2 diabetes found no increased risk of cancer with GLP-1 receptor agonist use. The overall odds ratio was 1.04 (95% CI 0.94–1.15, p=0.46), meaning cancer rates were essentially the same between GLP-1 users and controls.\n\nBreaking it down by drug: liraglutide (OR 1.08, p=0.38), exenatide (OR 1.00, p=1.00), semaglutide (OR 0.89, p=0.80), and albiglutide (OR 1.07, p=0.93) all showed no increased risk. A subanalysis of trials lasting more than 3 years also found no signal (OR 1.03, p=0.60).\n\nStatistical heterogeneity was low across all comparisons, strengthening confidence in the finding.","whyItMatters":"Animal studies had raised concerns about GLP-1 drugs potentially causing thyroid tumors, leading to persistent worry about cancer risk. This large meta-analysis of human trial data provides strong reassurance: across more than 50,000 patients and multiple drugs, there was no evidence of increased cancer risk. This is critical safety information for the millions of people now taking these medications for diabetes and weight loss.","specificNumbers":"N=50,452 · 34 RCTs · OR 1.04 (95% CI 0.94–1.15) overall · p=0.46 · Low heterogeneity · >3-year subanalysis: OR 1.03","methodology":"Systematic review and meta-analysis of randomized controlled trials (≥24 weeks duration) from MEDLINE, Embase, and Cochrane databases through October 2018. Included trials comparing GLP-1 receptor agonists to placebo or other diabetes drugs in type 2 diabetes patients, with cancer incidence as an outcome. Fixed effects model used to calculate odds ratios. Subanalyses by individual drug and by trial duration (>3 years).","limitations":"Cancer typically develops over many years, and even the 3+ year trials may be too short to detect a true long-term signal. The analysis focused on type 2 diabetes patients and may not apply to the obesity population now using these drugs. Individual cancer types were not analyzed separately. Published through 2018, so newer data from large cardiovascular outcome trials may not be fully captured."},{"rthcId":"RPEP-04348","title":"Collagen peptides promote photoaging skin cell repair by activating the TGF-β/Smad pathway and depressing collagen degradation.","authors":"Liu, Zehua; Li, Yuqi; Song, Hongdong; He, Juan; Li, Ge; Zheng, Yayao; Li, Bo","year":2019,"journal":"Food & function, 10(9), 6121-6134","doi":"10.1039/c9fo00610a","pmid":"31497829","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04349","title":"The Ancestral N-Terminal Domain of Big Defensins Drives Bacterially Triggered Assembly into Antimicrobial Nanonets.","authors":"Loth, Karine; Vergnes, Agnès; Barreto, Cairé; Voisin, Sébastien N; Meudal, Hervé; Da Silva, Jennifer; Bressan, Albert; Belmadi, Nawal; Bachère, Evelyne; Aucagne, Vincent; Cazevielle, Chantal; Marchandin, Hélène; Rosa, Rafael Diego; Bulet, Philippe; Touqui, Lhousseine; Delmas, Agnès F; Destoumieux-Garzón, Delphine","year":2019,"journal":"mBio, 10(5)","doi":"10.1128/mBio.01821-19","pmid":"31641083","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Cg-BigDef1 from oyster showed salt-stable, broad-spectrum bactericidal activity including against multidrug-resistant clinical MRSA isolates. The ancestral N-terminal domain — lost during evolution toward vertebrate beta-defensins — was essential: the C-terminal beta-defensin-like domain alone was inactive. Upon bacterial contact, the N-terminal domain drove Cg-BigDef1 self-assembly into nanonets that entrapped and killed bacteria. This nanonet formation represents a previously unknown antimicrobial mechanism. The salt stability is attributed to the hydrophobic N-terminal domain enabling membrane interactions in high-salt environments where electrostatic interactions are impaired.","whyItMatters":"The salt sensitivity of human defensins is one of the biggest obstacles to developing them as drugs. This study reveals that evolution actually solved this problem hundreds of millions of years ago — marine organisms retained a domain that confers salt-stable activity. By understanding how this ancient domain works (enabling hydrophobic rather than electrostatic membrane interactions), researchers can design new defensin variants that work at physiological salt concentrations. The nanonet killing mechanism is also entirely novel and could inspire new antimicrobial strategies.","specificNumbers":"","methodology":"Researchers produced Cg-BigDef1 and its separate N-terminal and C-terminal domains using native ligation chemistry. Antimicrobial activity was tested against multiple bacterial strains including multidrug-resistant clinical MRSA isolates at various salt concentrations. Nanonet assembly was visualized upon bacterial contact. NMR spectroscopy characterized the peptide structure. Each domain was tested independently to determine their individual contributions.","limitations":"The study focuses on an oyster peptide, and engineering similar properties into human defensin derivatives remains an undemonstrated challenge. The nanonet formation was observed in vitro — whether this mechanism operates in vivo is unknown. Production via native ligation chemistry, while enabling precise synthesis, may not scale for pharmaceutical manufacturing. Only MRSA was tested among drug-resistant strains."},{"rthcId":"RPEP-04350","title":"Glucagon-like peptide-1 receptor agonist exendin-4 mitigates lipopolysaccharide-induced inflammatory responses in RAW264.7 macrophages.","authors":"Lu, Canrong; Xie, Tianyu; Guo, Xin; Wu, Di; Li, Shuo; Li, Xiongguang; Lu, Yixun; Wang, Xinxin","year":2019,"journal":"International immunopharmacology, 77, 105969","doi":"10.1016/j.intimp.2019.105969","pmid":"31685436","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04351","title":"The Endocrine Function of the Heart: Physiology and Involvements of Natriuretic Peptides and Cyclic Nucleotide Phosphodiesterases in Heart Failure.","authors":"Lugnier, Claire; Meyer, Alain; Charloux, Anne; Andrès, Emmanuel; Gény, Bernard; Talha, Samy","year":2019,"journal":"Journal of clinical medicine, 8(10)","doi":"10.3390/jcm8101746","pmid":"31640161","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Under normal conditions, natriuretic peptides (ANP and BNP) are synthesized in response to atrial cardiomyocyte stretch and increase natriuresis, diuresis, and vascular permeability through cGMP-mediated signaling at specific receptors.\n\nIn heart failure, despite enhanced cardiac natriuretic peptide secretion, their beneficial effects are diminished due to renal resistance to NP action. A 'BNP paradox' exists: the BNP forms measured by current clinical assays may not represent the physiologically active forms, meaning high BNP levels in blood tests don't necessarily indicate effective peptide function. Inhibiting cyclic nucleotide phosphodiesterases (which degrade cGMP) represents a therapeutic strategy to improve natriuretic peptide system efficiency, with recent data supporting improved quality of life and prognosis in heart failure patients.","whyItMatters":"Heart failure affects millions worldwide and remains a leading cause of hospitalization and death. Understanding why the heart's own protective peptide system fails in heart failure — and how to restore it — could lead to better treatments. The BNP paradox also has diagnostic implications, as clinicians rely on BNP levels to assess heart failure severity, yet these measurements may not reflect actual peptide activity.","specificNumbers":"","methodology":"Narrative review of the physiology of cardiac natriuretic peptides, their signaling through cGMP pathways, the pathophysiology of natriuretic peptide resistance in heart failure, the BNP paradox, and the therapeutic potential of phosphodiesterase inhibitors to enhance natriuretic peptide signaling.","limitations":"This is a narrative review that does not present new experimental data. The BNP paradox is described conceptually but the specific inactive BNP forms are not fully characterized. The therapeutic potential of PDE inhibitors is discussed based on recent data but without specific clinical trial results in the abstract. The review focuses primarily on ANP and BNP without detailed coverage of other natriuretic peptide family members (CNP, urodilatin)."},{"rthcId":"RPEP-04352","title":"N-Terminal Liver-Expressed Antimicrobial Peptide 2 (LEAP2) Region Exhibits Inverse Agonist Activity toward the Ghrelin Receptor.","authors":"M'Kadmi, Céline; Cabral, Agustina; Barrile, Franco; Giribaldi, Julien; Cantel, Sonia; Damian, Marjorie; Mary, Sophie; Denoyelle, Séverine; Dutertre, Sébastien; Péraldi-Roux, Sylvie; Neasta, Jérémie; Oiry, Catherine; Banères, Jean-Louis; Marie, Jacky; Perello, Mario; Fehrentz, Jean-Alain","year":2019,"journal":"Journal of medicinal chemistry, 62(2), 965-973","doi":"10.1021/acs.jmedchem.8b01644","pmid":"30543423","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04353","title":"Antimicrobial Peptide LL-37 Facilitates Intracellular Uptake of RNA Aptamer Apt 21-2 Without Inducing an Inflammatory or Interferon Response.","authors":"Macleod, Tom; Ward, Joseph; Alase, Adewonuola A; Bridgewood, Charlie; Wittmann, Miriam; Stonehouse, Nicola J","year":2019,"journal":"Frontiers in immunology, 10, 857","doi":"10.3389/fimmu.2019.00857","pmid":"31068939","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04354","title":"Strategies for developing and optimizing cancer vaccines.","authors":"Maeng, Hoyoung M; Berzofsky, Jay A","year":2019,"journal":"F1000Research, 8","doi":"10.12688/f1000research.18693.1","pmid":"31131086","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Multiple cancer vaccine platforms have been developed over three decades, ranging from live viral/bacterial agents to synthetic peptide vaccines. Peptide vaccines — using short protein fragments that mimic cancer antigens — can elicit tumor-specific cellular and humoral immune responses, and have shown tumor regression or shrinkage in select trials. Nanoparticle delivery systems for peptide vaccines are an active area of development to improve immune recognition.\n\nHowever, cancer vaccines alone have achieved limited clinical success. The most promising approach is combining vaccines with other immunotherapies, particularly immune checkpoint inhibitors, to achieve reliable objective responses and survival benefit.","whyItMatters":"Peptide-based cancer vaccines represent one of the most direct applications of peptide science to life-threatening disease. Understanding the current state of this field — including why peptide vaccines have struggled as monotherapy and how new delivery technologies may change the picture — is important for anyone following the therapeutic potential of peptides in oncology.","specificNumbers":"","methodology":"Narrative review summarizing cancer vaccine platforms, delivery strategies, and optimization approaches across the field. Covers viral/bacterial vector vaccines, peptide vaccines, protein vaccines, DNA/RNA vaccines, dendritic cell vaccines, and combination strategies with checkpoint inhibitors.","limitations":"This is a narrative review without systematic methodology. It was published in 2019 and may not capture the most recent advances in mRNA cancer vaccines (which gained prominence during COVID-19) and neoantigen vaccine trials. The review covers many platforms broadly rather than providing deep analysis of peptide vaccines specifically."},{"rthcId":"RPEP-04355","title":"Association of polymorphisms of the β-defensin 1 gene with nematode and protozoan infection traits in goat.","authors":"Maia, Flora Suzane Parente; Campelo, José Elivalto Guimarães; Sarmento, José Lindemberg Rocha; Silva, Caio Santos; Marques, José Ribamar Felipe; Alves, Francisco Arimatéia Santos; Guimarães, Rafaelle Casseb; Filho, Ednaldo Silva","year":2019,"journal":"Parasite immunology, 41(4), e12613","doi":"10.1111/pim.12613","pmid":"30582754","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04356","title":"The limpet transcription factors of Triatoma infestans regulate the response to fungal infection and modulate the expression pattern of defensin genes.","authors":"Mannino, M Constanza; Paixão, Flávia R S; Pedrini, Nicolás","year":2019,"journal":"Insect biochemistry and molecular biology, 108, 53-60","doi":"10.1016/j.ibmb.2019.03.010","pmid":"30922828","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04357","title":"Snails In Silico: A Review of Computational Studies on the Conopeptides.","authors":"Mansbach, Rachael A; Travers, Timothy; McMahon, Benjamin H; Fair, Jeanne M; Gnanakaran, S","year":2019,"journal":"Marine drugs, 17(3)","doi":"10.3390/md17030145","pmid":"30832207","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04358","title":"A Clinical Approach for the Use of VIP Axis in Inflammatory and Autoimmune Diseases.","authors":"Martínez, Carmen; Juarranz, Yasmina; Gutiérrez-Cañas, Irene; Carrión, Mar; Pérez-García, Selene; Villanueva-Romero, Raúl; Castro, David; Lamana, Amalia; Mellado, Mario; González-Álvaro, Isidoro; Gomariz, Rosa P","year":2019,"journal":"International journal of molecular sciences, 21(1)","doi":"10.3390/ijms21010065","pmid":"31861827","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04359","title":"Caveolin-1-derived peptide limits development of pulmonary fibrosis.","authors":"Marudamuthu, Amarnath Satheesh; Bhandary, Yashodhar Prabhakar; Fan, Liang; Radhakrishnan, Vijay; MacKenzie, BreAnne; Maier, Esther; Shetty, Shwetha Kumari; Nagaraja, M R; Gopu, Venkadesaperumal; Tiwari, Nivedita; Zhang, Yajie; Watts, Alan B; Williams, Robert O; Criner, Gerald J; Bolla, Sudhir; Marchetti, Nathaniel; Idell, Steven; Shetty, Sreerama","year":2019,"journal":"Science translational medicine, 11(522)","doi":"10.1126/scitranslmed.aat2848","pmid":"31826982","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04360","title":"Design Principles for Intestinal Permeability of Cyclic Peptides.","authors":"Mathiowetz, Alan M","year":2019,"journal":"Methods in molecular biology (Clifton, N.J.), 2001, 1-15","doi":"10.1007/978-1-4939-9504-2_1","pmid":"31134564","tags":["cyclic-peptides","oral-bioavailability"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Cyclic peptides can achieve oral bioavailability despite violating traditional drug-likeness rules (Lipinski's Rule of 5), but they must be carefully designed for intestinal permeability. The key design principles fall into three categories: physical property guidelines (controlling size, flexibility, and lipophilicity), macrocyclic ring strategies (optimizing the backbone structure), and side chain strategies (minimizing solvent-exposed polarity).\n\nThe overarching goal is to reduce the peptide's exposure of polar chemical groups to the surrounding environment while keeping other properties in favorable ranges. This balancing act allows peptide chemists to achieve gut absorption alongside other critical drug properties like solubility and ability to bind their target.","whyItMatters":"Most peptide drugs must be injected because they can't survive the gut or cross the intestinal wall. This review lays out the design rules that are making oral peptide drugs possible — a development that could transform how peptide therapeutics are delivered. The success of oral semaglutide (Rybelsus) shows this isn't just theoretical; the design principles described here are actively enabling the next generation of oral peptide medicines.","specificNumbers":"3 design regimes · beyond Rule-of-5 chemistry · minimize solvent-exposed polarity","methodology":"Methods review covering design principles for intestinal permeability of cyclic peptides, including physical property guidelines, macrocyclic ring design strategies, and side chain optimization approaches developed in recent years.","limitations":"This is a methods review focused on design principles rather than clinical validation. Achieving intestinal permeability in the lab doesn't guarantee oral bioavailability in humans, as other factors like metabolic stability and first-pass liver effects also play critical roles."},{"rthcId":"RPEP-04361","title":"Identification of a Promiscuous Epitope Peptide Derived From HSP70.","authors":"Matsui, Hiroto; Hazama, Shoichi; Tamada, Koji; Udaka, Keiko; Irie, Atsushi; Nishimura, Yasuharu; Miyakawa, Tomoya; Doi, Shun; Nakajima, Masao; Kanekiyo, Shinsuke; Tokumitsu, Yukio; Shindo, Yoshitaro; Tomochika, Shinobu; Yoshida, Shin; Iida, Michihisa; Suzuki, Nobuaki; Takeda, Shigeru; Yamamoto, Shigeru; Yoshino, Shigefumi; Ueno, Tomio; Nagano, Hiroaki","year":2019,"journal":"Journal of immunotherapy (Hagerstown, Md. : 1997), 42(7), 244-250","doi":"10.1097/CJI.0000000000000274","pmid":"31398179","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04362","title":"Natriuretic peptides in human heart: Novel insight into their molecular forms, functions, and diagnostic use.","authors":"Matsuo, Ayaka; Nagai-Okatani, Chiaki; Nishigori, Mitsuhiro; Kangawa, Kenji; Minamino, Naoto","year":2019,"journal":"Peptides, 111, 3-17","doi":"10.1016/j.peptides.2018.08.006","pmid":"30120963","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04363","title":"Development of a M cell-targeted microparticulate platform, BSK02™, for oral immunization against the ovarian cancer antigen, sperm protein 17.","authors":"Mattila, Juha-Pekka; Mirandola, Leonardo; Chiriva-Internati, Maurizio","year":2019,"journal":"Journal of biomedical materials research. Part B, Applied biomaterials, 107(1), 29-36","doi":"10.1002/jbm.b.34092","pmid":"29504239","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Mice that received the oral microparticle vaccine showed strong activation of IFN-γ+/CD8+ T cells (cancer-killing immune cells) when re-exposed to the SP17 antigen. Vaccinated animals had significantly less ascites and tumor volume compared to placebo-treated animals four weeks after tumor challenge (p = 0.005).\n\nThe microparticles were engineered with enteric coatings to survive the stomach, sustained-release polymers for prolonged antigen exposure, and Aleuria aurantia lectin to specifically target M cells in the gut's immune tissue — making this a sophisticated oral delivery platform for peptide-based cancer immunotherapy.","whyItMatters":"Ovarian cancer is the fifth leading cause of cancer death in women and often recurs after initial treatment. An oral vaccine that can be swallowed rather than injected could make cancer immunotherapy more accessible and practical as a maintenance treatment. This study demonstrates that peptide antigens can be effectively delivered through the gut to generate meaningful anti-tumor immune responses.","specificNumbers":"","methodology":"Researchers created spray-dried microparticles containing an immunodominant peptide epitope from sperm protein 17 (SP17) along with a CpG oligonucleotide immune stimulant. The particles were coated with gut-targeting lectin and acid-resistant polymers. Mice were first challenged with SP17-expressing ovarian cancer cells (ID8 line), then given the oral vaccine one week later. Immune responses were measured by analyzing spleen cells for activated CD8+ T cells, and tumor burden was assessed by measuring ascites and tumor volume at four weeks.","limitations":"This was a mouse study using a xenograft tumor model, which does not fully replicate human ovarian cancer biology. The sample size details for the animal groups were not specified in the abstract. The long-term durability of the immune response and whether it could prevent recurrence over months or years was not assessed. Translation to humans faces significant hurdles including differences in gut immune system architecture."},{"rthcId":"RPEP-04364","title":"FKBPL and its peptide derivatives inhibit endocrine therapy resistant cancer stem cells and breast cancer metastasis by downregulating DLL4 and Notch4.","authors":"McClements, Lana; Annett, Stephanie; Yakkundi, Anita; O'Rourke, Martin; Valentine, Andrea; Moustafa, Nermeen; Alqudah, Abdelrahim; Simões, Bruno M; Furlong, Fiona; Short, Amy; McIntosh, Stuart A; McCarthy, Helen O; Clarke, Robert B; Robson, Tracy","year":2019,"journal":"BMC cancer, 19(1), 351","doi":"10.1186/s12885-019-5500-0","pmid":"30975104","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04365","title":"Human neutrophil peptide-1 inhibits thrombus formation under arterial flow via its terminal free cysteine thiols.","authors":"McDaniel, Jenny K; Abdelgawwad, Mohammad S; Hargett, Audra; Renfrow, Matthew B; Bdeir, Khalil; Cao, Wenjing; Cines, Douglas B; Zheng, X Long","year":2019,"journal":"Journal of thrombosis and haemostasis : JTH, 17(4), 596-606","doi":"10.1111/jth.14407","pmid":"30741476","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04366","title":"Peptide-targeted liposomal delivery of dexamethasone for arthritis therapy.","authors":"Meka, Rakeshchandra R; Venkatesha, Shivaprasad H; Acharya, Bodhraj; Moudgil, Kamal D","year":2019,"journal":"Nanomedicine (London, England), 14(11), 1455-1469","doi":"10.2217/nnm-2018-0501","pmid":"30938236","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04367","title":"Opposing effects of an atypical glycinergic and substance P transmission on interpeduncular nucleus plasticity.","authors":"Melani, Riccardo; Von Itter, Richard; Jing, Deqiang; Koppensteiner, Peter; Ninan, Ipe","year":2019,"journal":"Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 44(10), 1828-1836","doi":"10.1038/s41386-019-0396-6","pmid":"31005058","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Activation of substance P-positive neurons in the dorsomedial habenula causes simultaneous release of glutamate, glycine, and substance P in the lateral interpeduncular nucleus (LIPN). These co-released signals have opposing effects on synaptic plasticity: glycine receptor activity inhibits long-lasting potentiation of glutamatergic synapses, while substance P enhances it.\n\nSubstance P achieves this potentiation through a specific cascade: it triggers endocannabinoid CB1 receptor-mediated suppression of GABAB receptor activity, which disinhibits the system and allows substance P to produce a long-lasting increase in glutamate release. Behaviorally, NK1R (the substance P receptor) in the IPN was specifically required for fear extinction but not for the initial fear conditioning, demonstrating a selective role in fear unlearning.","whyItMatters":"Fear extinction is the central mechanism behind exposure therapy for anxiety disorders and PTSD — the most effective behavioral treatment for these conditions. Understanding the molecular mechanisms that enable fear extinction could lead to drugs that enhance therapy outcomes. The discovery that substance P in a specific brain circuit selectively promotes fear extinction (without affecting fear learning) makes the NK1 receptor a potential therapeutic target for anxiety disorders, with the precision to enhance fear unlearning without disrupting other memory processes.","specificNumbers":"","methodology":"The study used electrophysiological recordings in mouse brain slices to measure synaptic plasticity in LIPN neurons. Optogenetic activation was used to stimulate specific substance P-positive dMHb neurons. Pharmacological tools targeted glycine receptors, NK1 receptors (substance P receptor), CB1 endocannabinoid receptors, and GABAB receptors to dissect the signaling cascade. Behavioral experiments used fear conditioning and extinction paradigms with NK1R manipulations in the IPN.","limitations":"The study was conducted in mice, and direct translation to human brain circuitry requires caution. Electrophysiological recordings were performed in brain slices, which lack the full connectivity of intact circuits. The behavioral experiments targeted the NK1R specifically in the IPN, but substance P acts in many brain regions, so systemic NK1R manipulation may have different effects. The specific role of glycine co-release in fear behaviors was not directly tested behaviorally. Sample sizes for electrophysiology experiments were not detailed in the abstract."},{"rthcId":"RPEP-04368","title":"Effect of intranasal oxytocin on alcohol withdrawal syndrome: A randomized placebo-controlled double-blind clinical trial.","authors":"Melby, Katrine; Gråwe, Rolf W; Aamo, Trond O; Salvesen, Øyvind; Spigset, Olav","year":2019,"journal":"Drug and alcohol dependence, 197, 95-101","doi":"10.1016/j.drugalcdep.2019.01.003","pmid":"30784955","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04369","title":"Neurokinin-1 Receptor Deficiency Improves Survival in Murine Polymicrobial Sepsis Through Multiple Mechanisms in Aged Mice.","authors":"Mella, Juan R; Stucchi, Arthur F; Duffy, Elizabeth R; Remick, Daniel G","year":2019,"journal":"Shock (Augusta, Ga.), 52(1), 61-66","doi":"10.1097/SHK.0000000000001248","pmid":"30095600","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04370","title":"Alteration of the phagocytosis and antimicrobial defense of Octodonta nipae (Coleoptera: Chrysomelidae) pupae to Escherichia coli following parasitism by Tetrastichus brontispae (Hymenoptera: Eulophidae).","authors":"Meng, E; Li, J; Tang, B; Hu, Y; Qiao, T; Hou, Y; Lin, Y; Chen, Z","year":2019,"journal":"Bulletin of entomological research, 109(2), 248-256","doi":"10.1017/S0007485318000780","pmid":"30514411","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04371","title":"Innervation of the thoracolumbar fascia.","authors":"Mense, Siegfried","year":2019,"journal":"European journal of translational myology, 29(3), 8297","doi":"10.4081/ejtm.2019.8297","pmid":"31579474","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04372","title":"Bone mineral density response rates are greater in patients treated with abaloparatide compared with those treated with placebo or teriparatide: Results from the ACTIVE phase 3 trial.","authors":"Miller, P D; Hattersley, G; Lau, E; Fitzpatrick, L A; Harris, A G; Williams, G C; Hu, M-Y; Riis, B J; Russo, L; Christiansen, C","year":2019,"journal":"Bone, 120, 137-140","doi":"10.1016/j.bone.2018.10.015","pmid":"30359763","tags":["osteoporosis","bone-health"],"studyType":"randomized-controlled-trial","evidenceStrength":"strong","keyFinding":"In the ACTIVE phase 3 trial, the peptide drug abaloparatide produced significantly higher bone mineral density (BMD) response rates than both placebo and teriparatide at all time points and thresholds measured.\n\nAt 18 months, 44.5% of abaloparatide patients achieved >3% BMD gains at all three skeletal sites (total hip, femoral neck, and lumbar spine) compared to just 32.0% for teriparatide and 1.9% for placebo. The superiority was evident as early as 6 months: 19.1% of abaloparatide patients were responders versus 6.5% for teriparatide and 0.9% for placebo. Results were consistent across the >0%, >3%, and >6% response thresholds.","whyItMatters":"For postmenopausal women with severe osteoporosis, not just average bone density gain matters — what matters is what proportion of patients actually respond well to treatment. This analysis shows that abaloparatide produces meaningful bone density improvement in a larger proportion of patients than teriparatide (the existing peptide standard). Since abaloparatide is a 34-amino-acid peptide that selectively targets a specific conformation of the PTH receptor, it represents a next-generation peptide approach to bone building.","specificNumbers":"18-month phase 3 trial · >3% BMD responders at 18 months: abaloparatide 44.5% vs teriparatide 32.0% vs placebo 1.9% · At 6 months: 19.1% vs 6.5% vs 0.9% · Measured at total hip, femoral neck, and lumbar spine","methodology":"Prospective, exploratory responder analysis from the ACTIVE phase 3 trial (NCT01343004). Postmenopausal women with osteoporosis were randomized to abaloparatide, teriparatide, or placebo for 18 months. BMD was measured at total hip, femoral neck, and lumbar spine at 6, 12, and 18 months. Responders were defined as patients achieving BMD gains at all three sites simultaneously.","limitations":"This is an exploratory (not pre-specified primary) analysis of the ACTIVE trial. The responder definition requiring gains at all three sites is stringent and may not reflect clinical significance at individual sites. The trial was industry-sponsored (Radius Health, maker of abaloparatide). The study enrolled only postmenopausal women, so results may not generalize to men or premenopausal osteoporosis."},{"rthcId":"RPEP-04373","title":"Cell-Membrane Penetration of Tat-Conjugated Polymeric Micelles: Effect of Tat Coating Density.","authors":"Ming, Yang; Xiao, Yao; Tian, Yuan; Zhou, Shaobing","year":2019,"journal":"Macromolecular bioscience, 19(4), e1800364","doi":"10.1002/mabi.201800364","pmid":"30625260","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Both energy-dependent and energy-independent pathways were involved in the cellular uptake of Tat-conjugated polymeric micelles. At initial contact, Tat-conjugated micelles strongly accumulated on the cell surface before internalization.\n\nCritically, increasing Tat coating density had two effects: it increased both the membrane-anchoring rate and the internalization rate, and it accelerated the energy-independent (direct translocation) pathway. This means higher Tat density doesn't just get more particles inside cells — it fundamentally changes how they enter, favoring the direct penetration route that bypasses endosomal trapping.","whyItMatters":"Understanding exactly how surface peptide density affects nanoparticle entry into cells is crucial for designing effective drug delivery systems. This study provides actionable design rules: by tuning the amount of Tat peptide on a nanoparticle, researchers can control not just how efficiently it enters cells but which pathway it uses — potentially avoiding the endosome trap that degrades many delivered drugs before they can work.","specificNumbers":"","methodology":"Researchers prepared PEG-PCL (polyethylene glycol-polycaprolactone) polymeric micelles with varying densities of Tat peptide on their surface. They systematically varied Tat coating density, incubation concentrations, incubation time, and other factors. Cellular uptake was studied in multiple human cell lines (A549, HeLa, HepG2). Energy-dependent versus energy-independent uptake pathways were distinguished through controlled experimental conditions.","limitations":"This is an in vitro study using cultured human cell lines, which may not reflect the complexity of in vivo environments including the immune system, blood flow, and tissue barriers. The study did not test whether the observed differences in uptake mechanism translate to improved drug delivery efficacy. Long-term toxicity of high-density Tat coating was not assessed. Results from immortalized cancer cell lines may not generalize to all cell types."},{"rthcId":"RPEP-04374","title":"Multi-functionPlantDefensin,AntimicrobialandHeavyMetal Adsorbent Peptide.","authors":"Mirakhorli, Neda; Norolah, Zahra; Foruzandeh, Samira; Shafizade, Fateme; Nikookhah, Farzaneh; Saffar, Behnaz; Ansari, Omid","year":2019,"journal":"Iranian journal of biotechnology, 17(3), e1562","doi":"10.29252/ijb.1562","pmid":"32195280","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04375","title":"An in silico-in vitro Pipeline Identifying an HLA-A*02:01+ KRAS G12V+ Spliced Epitope Candidate for a Broad Tumor-Immune Response in Cancer Patients.","authors":"Mishto, Michele; Mansurkhodzhaev, Artem; Ying, Ge; Bitra, Aruna; Cordfunke, Robert A; Henze, Sarah; Paul, Debdas; Sidney, John; Urlaub, Henning; Neefjes, Jacques; Sette, Alessandro; Zajonc, Dirk M; Liepe, Juliane","year":2019,"journal":"Frontiers in immunology, 10, 2572","doi":"10.3389/fimmu.2019.02572","pmid":"31803176","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The pipeline identified a KRAS G12V mutation-carrying spliced epitope that is produced by proteasomes, transported by TAP proteins, and efficiently presented on cell surfaces by HLA-A*02:01 complexes — the most prevalent HLA class I molecule.\n\nThis is significant because conventional (non-spliced) peptides from the KRAS G12V mutation have low affinity for predominant HLA types, limiting their use in immunotherapy to only a few patients. By leveraging the much larger diversity of proteasome-generated spliced peptides, this approach could enable T cell-based immunotherapies targeting KRAS mutations in large cohorts of cancer patients.","whyItMatters":"KRAS mutations are among the most common cancer-driving mutations, found in pancreatic, colorectal, and lung cancers. However, targeting them with immunotherapy has been challenging because the mutated peptides don't display well on common HLA types. This pipeline opens up a new strategy — using spliced peptides — that dramatically expands the pool of targetable epitopes and the number of patients who could benefit from KRAS-directed immunotherapy.","specificNumbers":"","methodology":"The researchers developed an in silico-in vitro pipeline that first computationally predicted which spliced peptides carrying the KRAS G12V mutation would bind strongly to HLA-A*02:01. They then validated the candidates experimentally, confirming that the identified peptide is produced by proteasomes, transported by TAP proteins, and efficiently presented on HLA-A*02:01 complexes. The study used structural modeling and binding assays as part of the validation.","limitations":"This is a proof-of-principle study; the identified spliced epitope has not been tested for its ability to activate T cells in cancer patients. The pipeline's predictions need validation in clinical settings. The study focused on a single mutation (KRAS G12V) and a single HLA allele (HLA-A*02:01). The efficiency of spliced peptide generation by proteasomes in tumor cells in vivo remains to be confirmed. No clinical or animal model data were presented."},{"rthcId":"RPEP-04376","title":"Metabolism of atrial and brain natriuretic peptides in the fetoplacental circulation of fetuses with congenital heart diseases.","authors":"Miyoshi, Takekazu; Hosoda, Hiroshi; Miyazato, Mikiya; Kangawa, Kenji; Yoshimatsu, Jun; Minamino, Naoto","year":2019,"journal":"Placenta, 83, 26-32","doi":"10.1016/j.placenta.2019.06.382","pmid":"31477203","tags":["natriuretic-peptides","fetal-circulation","biomarkers"],"studyType":"Clinical (Observational/Cross-Sectional)","evidenceStrength":"Moderate","keyFinding":"The mother and fetus independently produce and metabolize natriuretic peptides (ANP and BNP) — their circulations do not share these peptide hormones. In 244 fetal samples (86 with congenital heart defects, 31 with arrhythmia, 127 controls), there was no correlation between maternal and fetal levels of either ANP or BNP.\n\nA key difference emerged between the two peptides: fetal ANP exists exclusively in its mature form and is rapidly metabolized by the placenta and umbilical vessels (umbilical vein levels were roughly double arterial levels). Fetal BNP, however, circulates predominantly as precursor forms (proBNP, glycosylated variants), which may protect it from placental degradation — BNP levels were similar between umbilical vein and artery. This has important implications for using natriuretic peptides as biomarkers for fetal heart disease.","whyItMatters":"Natriuretic peptides are the gold standard biomarkers for heart failure in adults, but their behavior in the fetal-placental circulation was poorly understood. This study shows that the placenta creates a complete barrier between maternal and fetal natriuretic peptide systems and actively metabolizes fetal ANP. This matters for prenatal diagnosis: measuring BNP (which survives placental metabolism) may be more reliable than ANP for assessing fetal cardiac stress from congenital heart defects.","specificNumbers":"n=244 (86 congenital heart defect, 31 arrhythmia, 127 controls) · ANP regression coefficient UV:UA ≈ 0.5 · BNP regression coefficient UV:UA ≈ 1.0 · no maternal-fetal correlation · ANP = mature form only · BNP = predominantly precursor forms","methodology":"Prospective cross-sectional study measuring plasma ANP and BNP concentrations in maternal vein, umbilical artery (UA), and umbilical vein (UV) samples. Three fetal groups were compared: congenital heart defects, arrhythmias, and normal controls. Molecular forms of immunoreactive ANP and BNP in UA plasma were characterized by chromatographic analysis.","limitations":"Cross-sectional design captures a single time point and cannot track changes over gestational age. The study focused on metabolic patterns rather than diagnostic accuracy for specific congenital heart defects. Molecular form analysis was performed on UA plasma only. The mechanism of placental ANP degradation is inferred from concentration gradients rather than directly measured. Sample sizes within specific congenital heart defect subtypes may be small."},{"rthcId":"RPEP-04377","title":"Adherence, persistence, glycaemic control and costs among patients with type 2 diabetes initiating dulaglutide compared with liraglutide or exenatide once weekly at 12-month follow-up in a real-world setting in the United States.","authors":"Mody, Reema; Huang, Qing; Yu, Maria; Zhao, Ruizhi; Patel, Hiren; Grabner, Michael; Landó, Laura Fernández","year":2019,"journal":"Diabetes, obesity & metabolism, 21(4), 920-929","doi":"10.1111/dom.13603","pmid":"30520248","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04378","title":"Efficacy and safety of oral semaglutide in patients with type 2 diabetes and moderate renal impairment (PIONEER 5): a placebo-controlled, randomised, phase 3a trial.","authors":"Mosenzon, Ofri; Blicher, Thalia Marie; Rosenlund, Signe; Eriksson, Jan W; Heller, Simon; Hels, Ole Holm; Pratley, Richard; Sathyapalan, Thozhukat; Desouza, Cyrus","year":2019,"journal":"The lancet. Diabetes & endocrinology, 7(7), 515-527","doi":"10.1016/S2213-8587(19)30192-5","pmid":"31189517","tags":["semaglutide","glp-1-agonist"],"studyType":"randomized-controlled-trial","evidenceStrength":"strong","keyFinding":"At 26 weeks, oral semaglutide 14 mg reduced HbA1c by 1.0 percentage point versus 0.2 for placebo (treatment difference: -0.8 percentage points; p<0.0001). Body weight decreased by 3.7 kg with semaglutide versus 1.1 kg with placebo (treatment difference: -2.7 kg; p<0.0001).\n\nIn the on-treatment analysis (excluding patients who discontinued or needed rescue medication), the HbA1c reduction was even larger: -1.1 versus -0.1 percentage points. Completion rates were 82% for semaglutide and 88% for placebo. More patients discontinued semaglutide due to adverse events (15% vs 5%), primarily gastrointestinal symptoms. Renal safety was consistent with the GLP-1 receptor agonist class.","whyItMatters":"Kidney impairment is extremely common in type 2 diabetes and narrows treatment options because many drugs are cleared through the kidneys. This trial established that oral semaglutide works effectively and safely in this vulnerable population, giving clinicians a new oral option where previously they might have had to rely on insulin or fewer alternatives. It was a key step in the PIONEER program that led to oral semaglutide's broad approval.","specificNumbers":"n=324; HbA1c ETD: -0.8 percentage points (p<0.0001); weight ETD: -2.7 kg (p<0.0001); 82% semaglutide completion; 15% discontinuation due to AEs","methodology":"Randomized, double-blind, placebo-controlled phase 3a trial at 88 sites across 8 countries. Patients with type 2 diabetes and moderate renal impairment (eGFR 30-59) on stable background medication were assigned 1:1 to oral semaglutide (escalated to 14 mg daily) or placebo for 26 weeks. Primary endpoint was change in HbA1c; confirmatory secondary endpoint was change in body weight. Two estimands were used: treatment policy and trial product.","limitations":"26-week duration only; no long-term renal or cardiovascular outcomes. Novo Nordisk funded. 15% semaglutide discontinuation rate due to adverse events. Moderate renal impairment only (eGFR 30-59). Elderly population (mean age 70)."},{"rthcId":"RPEP-04379","title":"Kinetics-Based Structural Requirements of Human Immunoglobulin G Binding Peptides.","authors":"Muguruma, Kyohei; Fujita, Konomi; Fukuda, Akane; Kishimoto, Satoshi; Sakamoto, Soichiro; Arima, Risako; Ito, Mayu; Kawasaki, Mayu; Nakano, Shogo; Ito, Sohei; Shimizu, Kanade; Taguchi, Akihiro; Takayama, Kentaro; Taniguchi, Atsuhiko; Ito, Yuji; Hayashi, Yoshio","year":2019,"journal":"ACS omega, 4(11), 14390-14397","doi":"10.1021/acsomega.9b01104","pmid":"31528791","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04380","title":"Tlr1-13, Nod1/2 and antimicrobial gene expression in the epididymis and testis of rats with alloxan-induced diabetes.","authors":"Munipalli, Suresh Babu; Mounika, Marri Reddy; Aisha, Jamil; Yenugu, Suresh","year":2019,"journal":"Andrologia, 51(11), e13437","doi":"10.1111/and.13437","pmid":"31637753","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Diabetes significantly altered the expression of multiple antimicrobial peptide genes in the male reproductive tract:\n- β-defensins (Defb1, 2, 21, 24, 27, 30) showed perturbed expression in the caput, cauda, and testis of diabetic rats\n- Spag11 family antimicrobial proteins (Spag11a, c, t) were also disrupted\n- Toll-like receptors (Tlr1-13) and NOD1/2 innate immune receptors showed altered expression patterns\n- Insulin treatment could only modulate expression of some, not all, of these genes, suggesting permanent or insulin-independent damage to the innate immune defense system","whyItMatters":"Diabetes affects over 400 million people worldwide, and male reproductive health complications — including increased infections, reduced fertility, and sexual dysfunction — are common but understudied consequences. This study identifies a specific mechanism: diabetes disrupts the antimicrobial peptide defense system in the reproductive tract. Understanding this could lead to targeted therapies to protect male reproductive health in diabetic patients.","specificNumbers":"","methodology":"Alloxan-induced diabetic rats were divided into three groups: diabetic (untreated), diabetic with insulin treatment, and healthy controls. Gene expression of Tlr1-13, Nod1/2, β-defensins (Defb1, 2, 21, 24, 27, 30), and Spag11 isoforms (a, c, t) was measured in the caput epididymis, cauda epididymis, and testis of each group.","limitations":"This is an animal study using chemically induced diabetes (alloxan), which causes type 1-like diabetes rather than the more common type 2 diabetes. Gene expression changes were measured at the mRNA level but protein levels and actual antimicrobial function were not assessed. The study did not directly test whether the AMP changes lead to increased susceptibility to infection. Sample sizes per group were not specified in the abstract."},{"rthcId":"RPEP-04381","title":"Impact of reproductive aging on the vaginal microbiome and soluble immune mediators in women living with and at-risk for HIV infection.","authors":"Murphy, Kerry; Keller, Marla J; Anastos, Kathryn; Sinclair, Shada; Devlin, J Cooper; Shi, Qiuhu; Hoover, Donald R; Starkman, Brian; McGillick, Jamie; Mullis, Caroline; Minkoff, Howard; Dominguez-Bello, Maria Gloria; Herold, Betsy C","year":2019,"journal":"PloS one, 14(4), e0216049","doi":"10.1371/journal.pone.0216049","pmid":"31026271","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04382","title":"Engineering NaV1.7 Inhibitory JzTx-V Peptides with a Potency and Basicity Profile Suitable for Antibody Conjugation To Enhance Pharmacokinetics.","authors":"Murray, Justin K; Wu, Bin; Tegley, Christopher M; Nixey, Thomas E; Falsey, James R; Herberich, Brad; Yin, Li; Sham, Kelvin; Long, Jason; Aral, Jennifer; Cheng, Yuan; Netirojjanakul, Chawita; Doherty, Liz; Glaus, Charles; Ikotun, Tayo; Li, Hongyan; Tran, Linh; Soto, Marcus; Salimi-Moosavi, Hossein; Ligutti, Joseph; Amagasu, Shanti; Andrews, Kristin L; Be, Xuhai; Lin, Min-Hwa Jasmine; Foti, Robert S; Ilch, Christopher P; Youngblood, Beth; Kornecook, Thomas J; Karow, Margaret; Walker, Kenneth W; Moyer, Bryan D; Biswas, Kaustav; Miranda, Les P","year":2019,"journal":"ACS chemical biology, 14(4), 806-818","doi":"10.1021/acschembio.9b00183","pmid":"30875193","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04383","title":"Sensory Neuropeptides and their Receptors Participate in Mechano-Regulation of Murine Macrophages.","authors":"Muschter, Dominique; Beiderbeck, Anna-Sophie; Späth, Tanja; Kirschneck, Christian; Schröder, Agnes; Grässel, Susanne","year":2019,"journal":"International journal of molecular sciences, 20(3)","doi":"10.3390/ijms20030503","pmid":"30682804","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04384","title":"The immune response of the scallop Argopecten purpuratus is associated with changes in the host microbiota structure and diversity.","authors":"Muñoz, K; Flores-Herrera, P; Gonçalves, A T; Rojas, C; Yáñez, C; Mercado, L; Brokordt, K; Schmitt, P","year":2019,"journal":"Fish & shellfish immunology, 91, 241-250","doi":"10.1016/j.fsi.2019.05.028","pmid":"31100440","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04385","title":"The involvement of the substance P/neurokinin 1 receptor system in viral infection: focus on the gp120 fusion protein and homologous dipeptide domains.","authors":"Muñoz, M; Coveñas, R; Kramer, M","year":2019,"journal":"Acta virologica, 63(3), 253-260","doi":"10.4149/av_2019_302","pmid":"31507190","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04386","title":"Prenatal ethanol exposure and enkephalinergic neurotransmission.","authors":"Méndez, Milagros; Hernández-Fonseca, Karla; Abate, Paula","year":2019,"journal":"Vitamins and hormones, 111, 313-337","doi":"10.1016/bs.vh.2019.05.005","pmid":"31421706","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04387","title":"Design, Synthesis, and Evaluation of a Diazirine Photoaffinity Probe for Ligand-Based Receptor Capture Targeting G Protein-Coupled Receptors.","authors":"Müskens, Frederike M; Ward, Richard J; Herkt, Dominik; van de Langemheen, Helmus; Tobin, Andrew B; Liskamp, Rob M J; Milligan, Graeme","year":2019,"journal":"Molecular pharmacology, 95(2), 196-209","doi":"10.1124/mol.118.114249","pmid":"30514721","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04388","title":"Prospects for a personalized peptide vaccine against lung cancer.","authors":"Nakahara, Yoshiro; Kouro, Taku; Igarashi, Yuka; Kawahara, Mamoru; Sasada, Tetsuro","year":2019,"journal":"Expert review of vaccines, 18(7), 703-709","doi":"10.1080/14760584.2019.1635461","pmid":"31225971","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04389","title":"Intracellular target delivery of cell-penetrating peptide-conjugated dodecaborate for boron neutron capture therapy (BNCT).","authors":"Nakase, Ikuhiko; Katayama, Miku; Hattori, Yoshihide; Ishimura, Miki; Inaura, Shunsuke; Fujiwara, Daisuke; Takatani-Nakase, Tomoka; Fujii, Ikuo; Futaki, Shiroh; Kirihata, Mitsunori","year":2019,"journal":"Chemical communications (Cambridge, England), 55(93), 13955-13958","doi":"10.1039/c9cc03924d","pmid":"31617510","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04390","title":"A randomized, double-blind, phase III trial of personalized peptide vaccination for recurrent glioblastoma.","authors":"Narita, Yoshitaka; Arakawa, Yoshiki; Yamasaki, Fumiyuki; Nishikawa, Ryo; Aoki, Tomokazu; Kanamori, Masayuki; Nagane, Motoo; Kumabe, Toshihiro; Hirose, Yuichi; Ichikawa, Tomotsugu; Kobayashi, Hiroyuki; Fujimaki, Takamitsu; Goto, Hisaharu; Takeshima, Hideo; Ueba, Tetsuya; Abe, Hiroshi; Tamiya, Takashi; Sonoda, Yukihiko; Natsume, Atsushi; Kakuma, Tatsuyuki; Sugita, Yasuo; Komatsu, Nobukazu; Yamada, Akira; Sasada, Tetsuro; Matsueda, Satoko; Shichijo, Shigeki; Itoh, Kyogo; Terasaki, Mizuhiko","year":2019,"journal":"Neuro-oncology, 21(3), 348-359","doi":"10.1093/neuonc/noy200","pmid":"30500939","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04391","title":"Patient selection for migraine preventive treatment with anti-CGRP(r) monoclonal antibodies.","authors":"Negro, Andrea; Martelletti, Paolo","year":2019,"journal":"Expert review of neurotherapeutics, 19(8), 769-776","doi":"10.1080/14737175.2019.1621749","pmid":"31109209","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Three first-in-class anti-CGRP monoclonal antibodies — erenumab, galcanezumab, and fremanezumab — have been approved for migraine prevention based on consistent phase 2 and phase 3 clinical trial data demonstrating both safety and efficacy for episodic and chronic migraine. These therapies offer advantages over conventional preventive treatments including rapid onset, sustained efficacy, a placebo-like safety profile, and no pharmacological interactions. However, the high cost of anti-CGRP mAbs makes careful patient selection essential to optimize treatment effectiveness and resource allocation.","whyItMatters":"Migraine is the leading cause of disability in people under 50, yet existing preventive drugs were originally developed for other conditions and have unclear mechanisms in migraine. Anti-CGRP monoclonal antibodies represent the first treatments specifically designed to target migraine pathophysiology, potentially transforming care for patients who fail conventional therapies.","specificNumbers":"","methodology":"This is an expert review article that synthesizes data from phase 2 and phase 3 clinical trials of three anti-CGRP monoclonal antibodies (erenumab, galcanezumab, and fremanezumab), evaluates the shortcomings of current preventive treatments, and discusses strategies for optimizing patient selection.","limitations":"As a narrative review rather than a systematic review or meta-analysis, the article relies on the authors' expert interpretation of existing trial data. Specific outcome numbers from the individual trials are not detailed in the abstract. Long-term safety and real-world effectiveness data were limited at the time of publication."},{"rthcId":"RPEP-04392","title":"Effect of semaglutide on liver enzymes and markers of inflammation in subjects with type 2 diabetes and/or obesity.","authors":"Newsome, Philip; Francque, Sven; Harrison, Stephen; Ratziu, Vlad; Van Gaal, Luc; Calanna, Salvatore; Hansen, Morten; Linder, Martin; Sanyal, Arun","year":2019,"journal":"Alimentary pharmacology & therapeutics, 50(2), 193-203","doi":"10.1111/apt.15316","pmid":"31246368","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04393","title":"Eradication of meticillin-resistant Staphylococcus aureus from human skin by the novel LL-37-derived peptide P10 in four pharmaceutical ointments.","authors":"Nibbering, Peter H; Göblyös, Anikó; Adriaans, Alwin E; Cordfunke, Robert A; Ravensbergen, Bep; Rietveld, Marion H; Zwart, Sarah; Commandeur, Suzan; van Leeuwen, Remko; Haisma, Elisabeth M; Schimmel, Kirsten J M; den Hartigh, Jan; Drijfhout, Jan Wouter; Ghalbzouri, Abdoelwaheb El","year":2019,"journal":"International journal of antimicrobial agents, 54(5), 610-618","doi":"10.1016/j.ijantimicag.2019.07.014","pmid":"31356860","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"P10, a novel peptide derived from LL-37, demonstrated dose-dependent killing of MRSA in multiple settings when formulated in hypromellose gel:\n\n- Remained chemically stable and antibacterially active at 4°C for 16 months in hypromellose gel\n- Reduced MRSA colonizing the stratum corneum (outer skin layer) on Leiden human epidermal models (LEMs)\n- Eradicated MRSA biofilms on LEMs\n- Dose-dependently reduced MRSA counts on ex-vivo human skin\n- Showed no adverse effects on human skin models\n\nHypromellose gel outperformed Cetomacrogol cream and Softisan cream as a delivery vehicle. Notably, some cream bases (Cetomacrogol with Vaseline, Softisan) were toxic to the skin models themselves, while hypromellose gel was safe.","whyItMatters":"MRSA infections are a growing global health crisis, and skin is one of the most common sites of infection. Current topical antibiotics like mupirocin face increasing resistance. Antimicrobial peptides derived from LL-37 offer a new approach because bacteria find it much harder to develop resistance to peptides that disrupt their membranes. This study demonstrates a complete preclinical package — stability, efficacy against both planktonic bacteria and biofilms, human skin compatibility, and an optimized formulation — bringing P10 closer to clinical development.","specificNumbers":"","methodology":"Researchers tested peptide P10 in four pharmaceutical ointment bases: hypromellose gel, Softisan-containing cream, Cetomacrogol cream, and Cetomacrogol cream with Vaseline. Chemical stability and antibacterial activity were assessed over 16 months at 4°C. Efficacy was tested on Leiden human epidermal models (LEMs) — lab-grown human skin equivalents — colonized with MRSA, including biofilm formation. Additional testing was performed on ex-vivo human skin samples. Toxicity to skin tissue was assessed for each formulation.","limitations":"Testing was performed on lab-grown skin models and ex-vivo skin, not in living patients. The antibacterial activity was assessed against a single MRSA strain; broader testing against diverse clinical isolates would strengthen the findings. No clinical trial data exists yet for P10. The requirement for refrigerated storage (4°C) may limit practical use in some settings. Cost of peptide synthesis for commercial production was not addressed."},{"rthcId":"RPEP-04394","title":"Clinical Significance of Increased Cardiac Troponin T in Patients with Chronic Hemodialysis and Cardiovascular Disease: Comparison to B-Type Natriuretic Peptide and A-Type Natriuretic Peptide Increase.","authors":"Niizuma, Shinichiro; Iwanaga, Yoshitaka; Washio, Takehiko; Ashida, Tadashi; Harasawa, Shinsuke; Miyazaki, Shunichi; Matsumoto, Naoya","year":2019,"journal":"Kidney & blood pressure research, 44(5), 1050-1062","doi":"10.1159/000502232","pmid":"31487705","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 174 chronic hemodialysis patients without acute coronary syndrome, troponin T (cTnT) correlated strongly with BNP (r=0.531, p<0.001) and ANP (r=0.411, p<0.001). However, elevated cTnT was not associated with the presence or extent of coronary artery disease (CAD), unlike BNP and ANP which were.\n\nAll three biomarkers correlated independently with left ventricular end-diastolic pressure (LVEDP) and were associated with NYHA heart failure classification and peripheral artery disease. For prognosis, both cTnT and BNP predicted mortality and heart failure hospitalization, but only BNP predicted vascular events. This indicates cTnT elevation in dialysis patients reflects myocardial stress (heart failure) rather than atherosclerotic disease.","whyItMatters":"Dialysis patients have extremely high cardiovascular mortality, and their cardiac biomarkers are frequently elevated even without a heart attack, making clinical decisions difficult. This study clarifies that troponin T elevation in these patients signals heart failure pressure overload rather than blocked arteries — a critical distinction for treatment decisions. Meanwhile, the natriuretic peptides BNP and ANP provide broader cardiovascular risk information.","specificNumbers":"","methodology":"Prospective observational study of 174 consecutive chronic hemodialysis patients referred for coronary angiography for stable CAD, peripheral artery disease, or heart failure. Hemodynamic measurements, coronary angiography, and simultaneous blood sampling for cTnT, BNP, and ANP were performed. Prognostic potential for all-cause mortality, cardiac death/heart failure hospitalization, and vascular events was assessed.","limitations":"This was a single-center observational study with a moderate sample size (174 patients). All patients were referred for coronary angiography, which may introduce referral bias. The study did not include serial biomarker measurements over time. The absence of high-sensitivity troponin assays (the newer standard) limits direct applicability to current practice. The results may not generalize to dialysis patients not referred for cardiac evaluation."},{"rthcId":"RPEP-04395","title":"Effects of Lyophilization of Arginine-rich Cell-penetrating Peptide-modified Extracellular Vesicles on Intracellular Delivery.","authors":"Noguchi, Kosuke; Hirano, Mami; Hashimoto, Takuya; Yuba, Eiji; Takatani-Nakase, Tomoka; Nakase, Ikuhiko","year":2019,"journal":"Anticancer research, 39(12), 6701-6709","doi":"10.21873/anticanres.13885","pmid":"31810935","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04396","title":"Effects of sacubitril/valsartan on neprilysin targets and the metabolism of natriuretic peptides in chronic heart failure: a mechanistic clinical study.","authors":"Nougué, Hélène; Pezel, Théo; Picard, François; Sadoune, Malha; Arrigo, Mattia; Beauvais, Florence; Launay, Jean-Marie; Cohen-Solal, Alain; Vodovar, Nicolas; Logeart, Damien","year":2019,"journal":"European journal of heart failure, 21(5), 598-605","doi":"10.1002/ejhf.1342","pmid":"30520545","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04397","title":"Apelin-36-[L28A] and Apelin-36-[L28C(30kDa-PEG)] peptides that improve diet induced obesity are G protein biased ligands at the apelin receptor.","authors":"Nyimanu, Duuamene; Kuc, Rhoda E; Williams, Thomas L; Bednarek, Maria; Ambery, Philip; Jermutus, Lutz; Maguire, Janet J; Davenport, Anthony P","year":2019,"journal":"Peptides, 121, 170139","doi":"10.1016/j.peptides.2019.170139","pmid":"31472173","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04398","title":"Tachykinins: Neuropeptides That Are Ancient, Diverse, Widespread and Functionally Pleiotropic.","authors":"Nässel, Dick R; Zandawala, Meet; Kawada, Tsuyoshi; Satake, Honoo","year":2019,"journal":"Frontiers in neuroscience, 13, 1262","doi":"10.3389/fnins.2019.01262","pmid":"31824255","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04399","title":"Endocrine regulation of gut function - a role for glucagon-like peptide-1 in the pathophysiology of irritable bowel syndrome.","authors":"O'Malley, Dervla","year":2019,"journal":"Experimental physiology, 104(1), 3-10","doi":"10.1113/EP087443","pmid":"30444291","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"L-cells in the gastrointestinal epithelium secrete GLP-1 in response to luminal factors — including short-chain fatty acids, bile acids, and microbial metabolites — that are specifically altered in IBS patients. GLP-1 can act as a hormone, paracrine factor, or neuromodulator, interacting with the HPA stress axis, immune system, and gut neurons, all of which are dysregulated in IBS.\n\nA GLP-1 mimetic has been found to alleviate acute pain symptoms in IBS patients, providing early clinical evidence that GLP-1 signaling may be important in IBS symptom manifestation. The review proposes that GLP-1 and L-cells function as signal transducers in the microbiome-gut-brain axis.","whyItMatters":"With millions of people now taking GLP-1 drugs for weight loss and diabetes, understanding GLP-1's effects on gut function is increasingly important. This review suggests these drugs may have unrecognized effects — positive or negative — on IBS symptoms. It also opens a new therapeutic avenue for IBS, a condition with limited effective treatments, by targeting a well-characterized peptide pathway.","specificNumbers":"","methodology":"This is a narrative review published in Experimental Physiology that synthesizes evidence from basic science, neuroendocrinology, and clinical observations to build the case for GLP-1's involvement in IBS pathophysiology. It examines L-cell biology, GLP-1 signaling pathways, and their intersection with known IBS pathophysiological mechanisms.","limitations":"As a review, no new experimental data is presented. The evidence linking GLP-1 to IBS is largely mechanistic and inferential — the clinical evidence is limited to one mention of a GLP-1 mimetic reducing IBS pain. The heterogeneity of IBS (different subtypes, triggers, and mechanisms) makes it difficult to assign a single peptide a central role. The review focuses on GLP-1 but IBS involves many other peptides and signaling molecules."},{"rthcId":"RPEP-04400","title":"Biomarkers in Atrial Fibrillation and Heart Failure.","authors":"Oikonomou, Evangelos; Zografos, Theodoros; Papamikroulis, Georgios-Angelos; Siasos, Gerasimos; Vogiatzi, Georgia; Theofilis, Panagiotis; Briasoulis, Alexandros; Papaioannou, Spyridon; Vavuranakis, Manolis; Gennimata, Vasiliki; Tousoulis, Dimitris","year":2019,"journal":"Current medicinal chemistry, 26(5), 873-887","doi":"10.2174/0929867324666170830100424","pmid":"28875838","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04401","title":"BNP as a Major Player in the Heart-Kidney Connection.","authors":"Okamoto, Ryuji; Ali, Yusuf; Hashizume, Ryotaro; Suzuki, Noboru; Ito, Masaaki","year":2019,"journal":"International journal of molecular sciences, 20(14)","doi":"10.3390/ijms20143581","pmid":"31336656","tags":["natriuretic-peptides"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"BNP (brain natriuretic peptide) plays a protective role in both the heart and kidneys, functioning as a key mediator of the heart-kidney connection. The review reveals that BNP levels are elevated in chronic kidney disease patients even without heart disease — a finding whose mechanism had been unclear. Evidence suggests the kidney's renal medulla produces depressor substances, and extracts from kidney papillary tips can actually stimulate cardiomyocytes (heart muscle cells) to produce and secrete more BNP.\n\nBNP appears to counteract the renin-angiotensin-aldosterone system (RAAS) — the hormonal system that raises blood pressure and promotes fluid retention — providing a natural protective mechanism against both heart failure and kidney disease progression.","whyItMatters":"Heart failure and kidney disease frequently occur together, creating a vicious cycle that accelerates both conditions. Understanding that BNP serves as a two-way protective signal between these organs helps explain why natriuretic peptide-based therapies (like sacubitril/valsartan) benefit both the heart and kidneys simultaneously. This knowledge is driving the development of treatments that harness the body's own peptide defense system.","specificNumbers":"Review article — synthesizes evidence on BNP's role in heart-kidney crosstalk","methodology":"This is a narrative review examining the molecular mechanisms of BNP in heart-kidney interactions. The authors synthesized evidence from basic science and clinical studies, focusing on BNP's relationship with the RAAS system, its expression patterns in cardiac and renal tissue, and the signaling pathways involved in its protective effects.","limitations":"As a narrative review rather than a systematic review, the evidence selection may not be comprehensive. The mechanism by which kidney extracts stimulate cardiac BNP production is described but not fully characterized. The review does not provide clinical trial data on BNP-targeted therapies."},{"rthcId":"RPEP-04402","title":"Oligoarginine-Bearing Tandem Repeat Penetration-Accelerating Sequence Delivers Protein to Cytosol via Caveolae-Mediated Endocytosis.","authors":"Okuda, Akiko; Tahara, Shinya; Hirose, Hisaaki; Takeuchi, Toshihide; Nakase, Ikuhiko; Ono, Atsushi; Takehashi, Masanori; Tanaka, Seigo; Futaki, Shiroh","year":2019,"journal":"Biomacromolecules, 20(5), 1849-1859","doi":"10.1021/acs.biomac.8b01299","pmid":"30893557","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The newly designed cell-penetrating peptide Pas2r12, consisting of a tandem repeat penetration-accelerating sequence (FFLIG-FFLIG) fused to d-dodeca-arginine (r12), significantly enhanced both cellular uptake and cytosolic release of two test proteins: enhanced green fluorescent protein (EGFP) and immunoglobulin G (IgG, an antibody).\n\nA key practical advantage is that Pas2r12 works by simple mixing with cargo proteins — no chemical cross-linking or conjugation is required to form delivery-competent complexes.\n\nMechanistic studies revealed the delivery process is energy-dependent, requires actin polymerization, and is specifically mediated by caveolae-mediated endocytosis. This was confirmed by inhibition with genistein and methyl-β-cyclodextrin (caveolae inhibitors) and siRNA knockdown of caveolin-1.","whyItMatters":"Most drugs that target processes inside cells are small molecules because proteins and antibodies are too large to cross cell membranes. A peptide that can deliver these large molecules into cells simply by mixing — without complex chemical modifications — could dramatically simplify intracellular drug delivery and unlock new therapeutic strategies, including intracellular antibody therapy.","specificNumbers":"","methodology":"Researchers designed and synthesized the Pas2r12 peptide, then tested its ability to deliver fluorescent protein (EGFP) and antibody (IgG) into cells. They used fluorescence microscopy and flow cytometry to measure cellular uptake and cytosolic release. To determine the entry mechanism, they tested energy dependence, actin polymerization inhibitors, caveolae-mediated endocytosis inhibitors (genistein, methyl-β-cyclodextrin), and siRNA against caveolin-1. Experiments were conducted in HEK293 cells.","limitations":"The study was conducted in a single cell line (HEK293) and may not generalize to other cell types, particularly primary cells or in vivo tissues. No toxicity or off-target effects were assessed. The efficiency of delivery was not quantified in absolute terms. No in vivo experiments were performed. The stability and pharmacokinetics of Pas2r12 in biological fluids are unknown."},{"rthcId":"RPEP-04403","title":"Lactobacillus reuteri DSM 17938 Protects against Gastric Damage Induced by Ethanol Administration in Mice: Role of TRPV1/Substance P Axis.","authors":"Oliveira, Ana P; Souza, Luan K M; Araújo, Thiago S L; Araújo, Simone de; Nogueira, Kerolayne M; Sousa, Francisca Beatriz M; Silva, Renan O; Pacífico, Dvison M; Martins, Conceição S; Brito, Gerly Anne de C; Souza, Marcellus H L P; Medeiros, Jand Venes R","year":2019,"journal":"Nutrients, 11(1)","doi":"10.3390/nu11010208","pmid":"30669695","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04404","title":"Negative correlation between testosterone and TNF-α in umbilical cord serum favors a weakened immune milieu in the human male fetoplacental unit.","authors":"Olmos-Ortiz, Andrea; García-Quiroz, Janice; Halhali, Ali; Avila, Euclides; Zaga-Clavellina, Verónica; Chavira-Ramírez, Roberto; García-Becerra, Rocío; Caldiño-Soto, Felipe; Larrea, Fernando; Díaz, Lorenza","year":2019,"journal":"The Journal of steroid biochemistry and molecular biology, 186, 154-160","doi":"10.1016/j.jsbmb.2018.10.009","pmid":"30359690","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04405","title":"Quantitative facial expression analysis revealed the efficacy and time course of oxytocin in autism.","authors":"Owada, Keiho; Okada, Takashi; Munesue, Toshio; Kuroda, Miho; Fujioka, Toru; Uno, Yota; Matsumoto, Kaori; Kuwabara, Hitoshi; Mori, Daisuke; Okamoto, Yuko; Yoshimura, Yuko; Kawakubo, Yuki; Arioka, Yuko; Kojima, Masaki; Yuhi, Teruko; Yassin, Walid; Kushima, Itaru; Benner, Seico; Ogawa, Nanayo; Kawano, Naoko; Eriguchi, Yosuke; Uemura, Yukari; Yamamoto, Maeri; Kano, Yukiko; Kasai, Kiyoto; Higashida, Haruhiro; Ozaki, Norio; Kosaka, Hirotaka; Yamasue, Hidenori","year":2019,"journal":"Brain : a journal of neurology, 142(7), 2127-2136","doi":"10.1093/brain/awz126","pmid":"31096266","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04406","title":"Inhibition of NLRP3 inflammasome activation by cell-permeable stapled peptides.","authors":"Pal, Arumay; Neo, Kurt; Rajamani, Lakshminarayanan; Ferrer, Fernando Jose; Lane, David P; Verma, Chandra S; Mortellaro, Alessandra","year":2019,"journal":"Scientific reports, 9(1), 4913","doi":"10.1038/s41598-019-41211-3","pmid":"30894604","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The stapled peptides achieved multiple validated effects in human monocytic cells (THP-1): they were effectively internalized, reduced ASC speck formation (the visible sign of inflammasome assembly), suppressed caspase-1 processing, and inhibited both pro-IL-1β processing and the release of active IL-1β and IL-18 following NLRP3 inflammasome activation.\n\nThe peptides were designed using molecular modeling guided by molecular dynamics simulations to adopt α-helical conformations that specifically target the pyrin domain of ASC. By disrupting ASC filament formation — a crucial structural step in inflammasome assembly — the peptides blocked the entire downstream inflammatory cascade. This represents the first successful proof-of-concept for stapled peptides targeting ASC in the NLRP3 pathway.","whyItMatters":"The NLRP3 inflammasome is implicated in a huge number of diseases affecting billions of people — atherosclerosis, diabetes, obesity, gout, Alzheimer's, and more. Current anti-IL-1β therapies (like the antibody canakinumab) are expensive and broadly immunosuppressive. Stapled peptides that specifically disrupt inflammasome assembly could offer more targeted anti-inflammatory therapy with potentially fewer side effects. This proof-of-concept opens a new therapeutic modality for inflammasome-driven diseases.","specificNumbers":"","methodology":"The researchers used computational molecular modeling and molecular dynamics simulations to design α-helical stapled peptides targeting the pyrin domain of the ASC adaptor protein. Peptide cellular uptake was assessed in human monocytic THP-1 cells. Functional validation included measuring IL-1β and IL-18 release, ASC speck formation, and caspase-1 processing following NLRP3 inflammasome activation with standard triggers (LPS priming + nigericin).","limitations":"All experiments were performed in vitro using a single cell line (THP-1 human monocytic cells). No in vivo animal testing was reported. The pharmacokinetics, stability, and potential off-target effects of these stapled peptides in living organisms are unknown. The specificity of the peptides for NLRP3 over other inflammasome types was not fully characterized. Manufacturing scalability and cost were not addressed."},{"rthcId":"RPEP-04407","title":"Nano-viscosimetry analysis of the membrane disrupting action of the bee venom peptide melittin.","authors":"Pandidan, Sara; Mechler, Adam","year":2019,"journal":"Scientific reports, 9(1), 10841","doi":"10.1038/s41598-019-47325-y","pmid":"31346251","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04408","title":"Personalized Peptide-based Vaccination for Treatment of Colorectal Cancer: Rational and Progress.","authors":"Parizadeh, Seyed Mostafa; Jafarzadeh-Esfehani, Reza; Ghandehari, Maryam; Rezaei-Kalat, Afsaneh; Parizadeh, Seyed Mohammad Reza; Javanbakht, Afsane; Hassanian, Seyed Mahdi; Ferns, Gordon A; Khazaei, Majid; Avan, Amir","year":2019,"journal":"Current drug targets, 20(14), 1486-1495","doi":"10.2174/1389450120666190619121658","pmid":"31237205","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Peptide-based vaccination therapy can induce tumor-specific immune responses by presenting antigen-derived peptides that help the immune system recognize and target cancer cells. This approach has emerged as a promising strategy particularly for colorectal cancer patients with advanced disease, where conventional treatments often fail due to drug resistance, toxicity, or incomplete tumor elimination.\n\nThe review highlights that personalized approaches — selecting peptides based on the clinicopathological and molecular features of individual tumors — may be more effective than one-size-fits-all vaccination strategies. When combined with conventional therapies, peptide vaccines could help eradicate residual micrometastases that lead to cancer recurrence.","whyItMatters":"Colorectal cancer has high mortality in advanced stages, and drug resistance limits the effectiveness of chemotherapy. Peptide vaccines offer a fundamentally different approach — instead of directly killing cancer cells, they reprogram the immune system to do it. Personalizing these vaccines to individual tumor profiles could make cancer immunotherapy more precise and effective, potentially preventing the recurrence that claims many patients' lives.","specificNumbers":"","methodology":"This is a narrative review article summarizing findings from recent clinical and preclinical studies on peptide-based vaccination therapy in colorectal cancer. The authors surveyed the literature on tumor antigen identification, peptide vaccine design, and clinical trial results in CRC patients.","limitations":"As a narrative review, this study synthesizes existing literature without presenting new data. Many of the clinical studies reviewed were early-phase trials with small sample sizes. The abstract does not discuss specific clinical outcomes or response rates, making it difficult to assess the current efficacy of peptide vaccines in CRC. The translation from promising preclinical results to effective clinical treatments remains a major challenge in this field."},{"rthcId":"RPEP-04409","title":"Effect of Stabilizers on Encapsulation Efficiency and Release Behavior of Exenatide-Loaded PLGA Microsphere Prepared by the W/O/W Solvent Evaporation Method.","authors":"Park, Heejun; Ha, Dong-Hyun; Ha, Eun-Sol; Kim, Jeong-Soo; Kim, Min-Soo; Hwang, Sung-Joo","year":2019,"journal":"Pharmaceutics, 11(12)","doi":"10.3390/pharmaceutics11120627","pmid":"31771254","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04410","title":"Cyclic Cell-Penetrating Peptides as Efficient Intracellular Drug Delivery Tools.","authors":"Park, Shang Eun; Sajid, Muhammad Imran; Parang, Keykavous; Tiwari, Rakesh Kumar","year":2019,"journal":"Molecular pharmaceutics, 16(9), 3727-3743","doi":"10.1021/acs.molpharmaceut.9b00633","pmid":"31329448","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04411","title":"The Medicinal Chemistry of Therapeutic Peptides: Recent Developments in Synthesis and Design Optimizations.","authors":"Parthasarathy, Anutthaman; Anandamma, Sasikala K; Kalesh, Karunakaran A","year":2019,"journal":"Current medicinal chemistry, 26(13), 2330-2355","doi":"10.2174/0929867324666171012103559","pmid":"29022499","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04412","title":"Incorporation of Putative Helix-Breaking Amino Acids in the Design of Novel Stapled Peptides: Exploring Biophysical and Cellular Permeability Properties.","authors":"Partridge, Anthony W; Kaan, Hung Yi Kristal; Juang, Yu-Chi; Sadruddin, Ahmad; Lim, Shuhui; Brown, Christopher J; Ng, Simon; Thean, Dawn; Ferrer, Fernando; Johannes, Charles; Yuen, Tsz Ying; Kannan, Srinivasaraghavan; Aronica, Pietro; Tan, Yaw Sing; Pradhan, Mohan R; Verma, Chandra S; Hochman, Jerome; Chen, Shiying; Wan, Hui; Ha, Sookhee; Sherborne, Brad; Lane, David P; Sawyer, Tomi K","year":2019,"journal":"Molecules (Basel, Switzerland), 24(12)","doi":"10.3390/molecules24122292","pmid":"31226791","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04413","title":"Cell-penetrating peptide sequence and modification dependent uptake and subcellular distribution of green florescent protein in different cell lines.","authors":"Patel, Sanjay G; Sayers, Edward J; He, Lin; Narayan, Rohan; Williams, Thomas L; Mills, Emily M; Allemann, Rudolf K; Luk, Louis Y P; Jones, Arwyn T; Tsai, Yu-Hsuan","year":2019,"journal":"Scientific reports, 9(1), 6298","doi":"10.1038/s41598-019-42456-8","pmid":"31000738","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04414","title":"Nasal Administration and Plasma Pharmacokinetics of Parathyroid Hormone Peptide PTH 1-34 for the Treatment of Osteoporosis.","authors":"Pearson, Richard G; Masud, Tahir; Blackshaw, Elaine; Naylor, Andrew; Hinchcliffe, Michael; Jeffery, Kirk; Jordan, Faron; Shabir-Ahmed, Anjumn; King, Gareth; Lewis, Andrew L; Illum, Lisbeth; Perkins, Alan C","year":2019,"journal":"Pharmaceutics, 11(6)","doi":"10.3390/pharmaceutics11060265","pmid":"31181662","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04415","title":"Repurposing the scorpion venom peptide VmCT1 into an active peptide against Gram-negative ESKAPE pathogens.","authors":"Pedron, Cibele Nicolaski; Araújo, Iris; da Silva Junior, Pedro Ismael; Dias da Silva, Fernanda; Torres, Marcelo Der Torossian; Oliveira Junior, Vani Xavier","year":2019,"journal":"Bioorganic chemistry, 90, 103038","doi":"10.1016/j.bioorg.2019.103038","pmid":"31212183","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04416","title":"Substance P and fibrotic diseases.","authors":"Peng, Lei; Agogo, George O; Guo, Jianqiang; Yan, Ming","year":2019,"journal":"Neuropeptides, 76, 101941","doi":"10.1016/j.npep.2019.101941","pmid":"31256921","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The Substance P/NK-1 receptor (SP/NK-1R) system is implicated in fibrotic processes across multiple organ systems, including wound healing, myocardial fibrosis, bowel fibrosis, myelofibrosis, renal fibrosis, lung fibrosis, and liver fibrosis.\n\nRecent studies have specifically demonstrated that Substance P plays an important role in liver fibrosis and that NK-1R antagonists can inhibit the progression of this fibrosis. The review proposes that NK-1R receptor antagonists could provide clinical solutions for treating fibrotic diseases more broadly.","whyItMatters":"Fibrotic diseases — where excessive scarring damages organs — affect millions of people and have limited treatment options. Identifying Substance P as a common driver across multiple types of fibrosis opens up a potentially unifying therapeutic strategy. Since NK-1R antagonists already exist (aprepitant is FDA-approved for nausea), there's a realistic path to repurposing these drugs for fibrotic conditions, which could accelerate clinical translation.","specificNumbers":"","methodology":"This is a narrative review article summarizing the existing literature on Substance P's structure, function, distribution, and involvement in fibrotic diseases across multiple organ systems. It synthesizes findings from preclinical and clinical studies.","limitations":"As a narrative review, this paper summarizes existing literature without performing a systematic search or meta-analysis, which may introduce selection bias. Most evidence for NK-1R antagonists inhibiting fibrosis comes from preclinical (animal or cell) studies. Clinical trials specifically testing NK-1R antagonists for fibrotic diseases in humans are largely absent from this review. The mechanisms described are still partially speculative."},{"rthcId":"RPEP-04417","title":"Novel insights into the role of urotensin II in cardiovascular disease.","authors":"Pereira-Castro, João; Brás-Silva, Carmen; Fontes-Sousa, Ana Patrícia","year":2019,"journal":"Drug discovery today, 24(11), 2170-2180","doi":"10.1016/j.drudis.2019.08.005","pmid":"31430542","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The UT receptor for urotensin II has unexpectedly complex biology that may explain failed clinical translation. Two endogenous ligands — UII and urotensin-related peptide (URP) — bind and activate the receptor differently. The receptor is not restricted to the plasma membrane but also exists intracellularly, potentially inducing different physiological responses. These properties could produce inconsistent but potent vasoactive effects, explaining why UT receptor antagonists showed promise in preclinical models of heart failure, pulmonary hypertension, atherosclerosis, and diabetes but failed to replicate these results in clinical studies.","whyItMatters":"UII was once considered one of the most exciting targets in cardiovascular peptide pharmacology. Understanding why it failed clinically is important not only for potentially reviving UII-based therapies with better approaches, but also as a cautionary lesson for other peptide drug development programs where complex receptor biology may confound straightforward antagonist strategies.","specificNumbers":"","methodology":"Narrative review synthesizing preclinical and clinical evidence on urotensin II signaling in cardiovascular disease, with particular focus on receptor pharmacology, ligand binding characteristics, and the discrepancy between preclinical and clinical outcomes.","limitations":"As a narrative review, the paper selectively covers the UII literature. The precise reasons for clinical trial failures are speculative based on preclinical observations. The review focuses on cardiovascular applications, though UII has roles in other systems. Some of the receptor biology described (intracellular localization) is based on limited evidence that needs further confirmation."},{"rthcId":"RPEP-04418","title":"Stable gastric pentadecapeptide BPC 157 can improve the healing course of spinal cord injury and lead to functional recovery in rats.","authors":"Perovic, Darko; Kolenc, Danijela; Bilic, Vide; Somun, Nenad; Drmic, Domagoj; Elabjer, Esmat; Buljat, Gojko; Seiwerth, Sven; Sikiric, Predrag","year":2019,"journal":"Journal of orthopaedic surgery and research, 14(1), 199","doi":"10.1186/s13018-019-1242-6","pmid":"31266512","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04419","title":"Migraine overview and summary of current and emerging treatment options.","authors":"Peters, Golden L","year":2019,"journal":"The American journal of managed care, 25(2 Suppl), S23-S34","doi":null,"pmid":"30681821","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04420","title":"Drug delivery systems designed to overcome antimicrobial resistance.","authors":"Pham, Thanh-Nhat; Loupias, Pauline; Dassonville-Klimpt, Alexandra; Sonnet, Pascal","year":2019,"journal":"Medicinal research reviews, 39(6), 2343-2396","doi":"10.1002/med.21588","pmid":"31004359","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04421","title":"Non-Peptidergic Nociceptive Neurons Are Essential for Mechanical Inflammatory Hypersensitivity in Mice.","authors":"Pinto, Larissa G; Souza, Guilherme R; Kusuda, Ricardo; Lopes, Alexandre H; Sant'Anna, Morena B; Cunha, Fernando Q; Ferreira, Sérgio H; Cunha, Thiago M","year":2019,"journal":"Molecular neurobiology, 56(8), 5715-5728","doi":"10.1007/s12035-019-1494-5","pmid":"30674034","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04422","title":"Analysis of hydrophobic and hydrophilic moments of short penetrating peptides for enhancing mitochondrial localization: prediction and validation.","authors":"Pirisinu, Marco; Blasco, Pilar; Tian, Xueli; Sen, Yang; Bode, Ann M; Liu, Kangdong; Dong, Zigang","year":2019,"journal":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 33(7), 7970-7984","doi":"10.1096/fj.201802748RR","pmid":"30917009","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04423","title":"Effects of Intracerebroventricular and Intra-Arcuate Nucleus Injection of Ghrelin on Pain Behavioral Responses and Met-Enkephalin and β-Endorphin Concentrations in the Periaqueductal Gray Area in Rats.","authors":"Pirzadeh, Samaneh; Sajedianfard, Javad; Aloisi, Anna Maria; Ashrafi, Mahboobeh","year":2019,"journal":"International journal of molecular sciences, 20(10)","doi":"10.3390/ijms20102475","pmid":"31109149","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Both intracerebroventricular (ICV) and intra-arcuate nucleus (ARC) injection of ghrelin significantly reduced pain behavioral scores across all phases of the formalin test (p < 0.01). Simultaneously, concentrations of met-enkephalin (MENK) and beta-endorphin (β-EP) in the periaqueductal gray area increased significantly following ghrelin injection. This demonstrates that ghrelin's pain-relieving effect operates through the arcuate nucleus and involves activation of the endogenous opioid system.","whyItMatters":"Understanding how peptides like ghrelin interact with the brain's natural pain pathways could lead to new, non-addictive pain treatments. Current opioid painkillers carry serious risks of addiction and overdose. If ghrelin or similar peptides can activate the body's own opioid system in a controlled way, they might offer pain relief with a better safety profile than synthetic opioids.","specificNumbers":"","methodology":"Thirty-five male rats were divided into five groups. Ghrelin was injected into either the left lateral ventricle (ICV, 5 µL) or the arcuate nucleus (ARC, 1 µL). Fifteen minutes later, formalin (2.5%) was injected into the left hind paw to induce pain. Behavioral pain scores were recorded for 60 minutes. Levels of met-enkephalin and beta-endorphin were collected from the periaqueductal gray area using microdialysis and measured by high-performance liquid chromatography (HPLC).","limitations":"This is an animal study in rats, and results may not directly translate to humans. The ghrelin was injected directly into the brain, which is not a practical clinical delivery method. The sample size of 35 rats across 5 groups (7 per group) is relatively small. The formalin test models acute inflammatory pain but does not capture chronic pain conditions. Long-term effects and potential side effects of brain ghrelin injection were not assessed."},{"rthcId":"RPEP-04424","title":"Mitochondrial peptides-appropriate options for therapeutic exploitation.","authors":"Popov, Lucia-Doina","year":2019,"journal":"Cell and tissue research, 377(2), 161-165","doi":"10.1007/s00441-019-03049-z","pmid":"31131430","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies three major categories of mitochondrial peptides with therapeutic potential:\n\n1. Mitochondrial-derived peptides (MDPs): Humanin, humanin-like peptides, and MOTS-c are encoded by mitochondrial DNA and serve as protective stress response factors. These peptides have shown cytoprotective and metabolic-regulating effects in preclinical studies.\n\n2. β-amyloid accumulation: The abnormal deposition of β-amyloid peptide within the mitochondrial matrix contributes to mitochondrial dysfunction in neurodegenerative diseases, representing both a disease mechanism and a therapeutic target.\n\n3. Mitochondrial-targeting peptides: Engineered cell-penetrating peptides that can deliver bioactive agents directly into dysfunctional mitochondria, offering a strategy to restore electron transport chain function and cellular energy production in disease states.","whyItMatters":"Mitochondrial dysfunction is implicated in an enormous range of diseases — Alzheimer's, Parkinson's, diabetes, heart disease, and aging itself. The discovery that mitochondria produce their own protective peptides opens a new therapeutic frontier. Meanwhile, the ability to engineer peptides that deliver drugs directly into mitochondria could provide treatments for conditions that were previously untreatable because drugs couldn't reach the right cellular compartment.","specificNumbers":"","methodology":"Narrative review synthesizing recent findings across three areas of mitochondrial peptide research: endogenous mitochondrial-derived peptides, pathological peptide accumulation in mitochondria, and engineered peptide delivery systems targeting mitochondria.","limitations":"As a brief narrative review, this paper provides an overview rather than a comprehensive systematic analysis. The therapeutic applications discussed are largely preclinical, with no clinical trial data presented. The review is limited in scope (5 pages) and does not deeply explore individual peptide mechanisms or the challenges of translating these findings to human therapy."},{"rthcId":"RPEP-04425","title":"Identification of a novel growth hormone releasing peptide (a glycine analogue of GHRP-2) in a seized injection vial.","authors":"Popławska, Magdalena; Błażewicz, Agata","year":2019,"journal":"Drug testing and analysis, 11(1), 162-167","doi":"10.1002/dta.2467","pmid":"30051972","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04426","title":"Oral Supplementation of Specific Collagen Peptides Combined with Calf-Strengthening Exercises Enhances Function and Reduces Pain in Achilles Tendinopathy Patients.","authors":"Praet, Stephan F E; Purdam, Craig R; Welvaert, Marijke; Vlahovich, Nicole; Lovell, Gregg; Burke, Louise M; Gaida, Jamie E; Manzanero, Silvia; Hughes, David; Waddington, Gordon","year":2019,"journal":"Nutrients, 11(1)","doi":"10.3390/nu11010076","pmid":"30609761","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Patients who received collagen peptides (TENDOFORTE®) for the first 3 months showed a VISA-A improvement of 12.6 points, compared to only 5.3 points in the placebo group over the same period. After crossover, the group switching to collagen peptides saw a dramatic 17.7-point increase, while the group switching to placebo showed only a 5.9-point increase. Tendon microvascularity decreased in both groups, moderately correlating with clinical improvement (Rc²=0.68). No adverse events were reported.","whyItMatters":"Achilles tendinopathy is a common, often chronic condition that limits activity and can take months to resolve even with structured exercise. Adding a simple oral collagen peptide supplement to a rehabilitation program appeared to roughly double the rate of clinical improvement, offering a safe, accessible way to accelerate recovery from this stubborn tendon problem.","specificNumbers":"","methodology":"Double-blind, crossover pilot study with 20 patients with chronic mid-portion Achilles tendinopathy. All participants did a bi-daily calf-strengthening and return-to-running program for 6 months. Group AB received collagen peptides for months 1–3 then placebo for months 4–6; Group BA received placebo then collagen peptides. VISA-A questionnaires and contrast-enhanced ultrasound were measured at baseline, 3, and 6 months.","limitations":"Small sample size (n=20) limits statistical power and generalizability. The crossover design means patients who received collagen first had already improved before switching to placebo, potentially complicating interpretation of the second phase. The study used a branded product (TENDOFORTE®), which may have specific characteristics not shared by generic collagen peptides. Longer follow-up beyond 6 months was not available."},{"rthcId":"RPEP-04427","title":"Targeting chronic lymphocytic leukemia with N-methylated thrombospondin-1-derived peptides overcomes drug resistance.","authors":"Pramil, Elodie; Herbi Bastian, Linda; Denèfle, Thomas; Nemati, Fariba; Xiao, Malina; Lardé, Eva; Maloum, Karim; Roos-Weil, Damien; Chapiro, Elise; Le Garff-Tavernier, Magali; Davi, Frédéric; Decaudin, Didier; Sarfati, Marika; Nguyen-Khac, Florence; Merle-Béral, Hélène; Karoyan, Philippe; Susin, Santos A","year":2019,"journal":"Blood advances, 3(20), 2920-2933","doi":"10.1182/bloodadvances.2019000350","pmid":"31648314","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04428","title":"Expression and Function of Host Defense Peptides at Inflammation Sites.","authors":"Prasad, Suhanya V; Fiedoruk, Krzysztof; Daniluk, Tamara; Piktel, Ewelina; Bucki, Robert","year":2019,"journal":"International journal of molecular sciences, 21(1)","doi":"10.3390/ijms21010104","pmid":"31877866","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Host defense peptides (HDPs), including cathelicidins and defensins, play complex dual roles at inflammation sites — acting as both pro-inflammatory and anti-inflammatory mediators depending on their concentration and context. HDPs provide constitutive protection against microorganisms but are also induced by inflammatory signals in various cells and tissues. Their physicochemical properties and interactions with multiple receptors determine whether they amplify or dampen inflammation. Impaired HDP expression is clinically relevant in several inflammatory diseases.","whyItMatters":"Understanding how HDPs function at inflammation sites is crucial for developing peptide-based therapies for inflammatory diseases. The dual pro/anti-inflammatory nature of these peptides explains why simply boosting HDPs isn't always beneficial — the dose, timing, and tissue context all matter. This complexity also reveals why HDP-based treatments must be carefully designed to harness their therapeutic potential without triggering unwanted inflammation.","specificNumbers":"Covers cathelicidins, defensins, and other HDP families · dual pro- and anti-inflammatory roles · expression varies by cell type and tissue · receptor-mediated immunomodulation · clinical relevance in multiple inflammatory diseases","methodology":"This is a comprehensive review of the literature on host defense peptide expression and function at sites of inflammation, covering constitutive and inducible expression, immunomodulatory mechanisms, and clinical relevance across various inflammatory conditions.","limitations":"As a review, no new experimental data are presented. The complexity of HDP functions makes it difficult to draw universal conclusions — effects vary by peptide type, concentration, tissue context, and disease state. Translating the dual-role biology of HDPs into therapeutic strategies remains challenging."},{"rthcId":"RPEP-04429","title":"Peptide conjugates of lactoferricin analogues and antimicrobials-Design, chemical synthesis, and evaluation of antimicrobial activity and mammalian cytotoxicity.","authors":"Ptaszyńska, Natalia; Olkiewicz, Katarzyna; Okońska, Joanna; Gucwa, Katarzyna; Łęgowska, Anna; Gitlin-Domagalska, Agata; Dębowski, Dawid; Lica, Jan; Heldt, Mateusz; Milewski, Sławomir; Ng, Tzi Bun; Rolka, Krzysztof","year":2019,"journal":"Peptides, 117, 170079","doi":"10.1016/j.peptides.2019.04.006","pmid":"30959143","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04430","title":"Development of Protein- and Peptide-Based HIV Entry Inhibitors Targeting gp120 or gp41.","authors":"Pu, Jing; Wang, Qian; Xu, Wei; Lu, Lu; Jiang, Shibo","year":2019,"journal":"Viruses, 11(8)","doi":"10.3390/v11080705","pmid":"31374953","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04431","title":"Decoding the human serum interactome of snake-derived antimicrobial peptide Ctn[15-34]: Toward an explanation for unusually long half-life.","authors":"Pérez-Peinado, Clara; Defaus, Sira; Sans-Comerma, Laura; Valle, Javier; Andreu, David","year":2019,"journal":"Journal of proteomics, 204, 103372","doi":"10.1016/j.jprot.2019.04.022","pmid":"31051282","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04432","title":"pH and Thermal Dual-Sensitive Nanoparticle-Mediated Synergistic Antitumor Effect of Immunotherapy and Microwave Thermotherapy.","authors":"Qi, Jing; Li, Weishuo; Lu, Kongjun; Jin, Feiyang; Liu, Di; Xu, Xiaoling; Wang, Xiaojuan; Kang, Xuqi; Wang, Wei; Shu, Gaofeng; Han, Feng; Ying, Xiaoying; You, Jian; Ji, Jiansong; Du, Yongzhong","year":2019,"journal":"Nano letters, 19(8), 4949-4959","doi":"10.1021/acs.nanolett.9b01061","pmid":"31286769","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04433","title":"PET Imaging of HER2-Positive Tumors with Cu-64-Labeled Affibody Molecules.","authors":"Qi, Shibo; Hoppmann, Susan; Xu, Yingding; Cheng, Zhen","year":2019,"journal":"Molecular imaging and biology, 21(5), 907-916","doi":"10.1007/s11307-018-01310-5","pmid":"30617730","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"All three Cu-64-labeled affibody variants demonstrated excellent HER2 targeting with similar tumor uptake at 24 hours (4.0-4.3 %ID/g). The binding affinities were in the low nanomolar range: [64Cu]DOTA-Cys-ZHER2:342 (KD = 25.2 ± 9.2 nM) showed the strongest binding, followed by the C-terminal variant (32.6 ± 14.7 nM) and the internal variant (77.6 ± 22.2 nM).\n\nThe N-terminal labeled probe ([64Cu]DOTA-Cys-ZHER2:342) also demonstrated the highest in vivo stability. Specificity was confirmed by co-injecting unlabeled affibody, which reduced tumor uptake. All probes showed fast tumor targeting, good tumor accumulation, and good tumor-to-normal tissue contrast on PET imaging.","whyItMatters":"HER2 status guides treatment decisions in breast and ovarian cancer, but current detection methods rely on biopsies. Non-invasive PET imaging with peptide-based probes could allow doctors to determine HER2 status across all tumor sites in the body simultaneously, track changes over time, and guide therapy selection — all without surgery. Small affibody peptides offer advantages over full antibody-based imaging agents, including faster blood clearance and earlier imaging timepoints.","specificNumbers":"","methodology":"Three affibody variants were synthesized using solid-phase peptide synthesis, each with the radioactive label attached at a different position (N-terminal, C-terminal, or internal). They were conjugated with a DOTA chelator and radiolabeled with Cu-64. Cell uptake, binding affinity, and stability were tested in vitro using HER2-positive SKOV3 ovarian cancer cells. In vivo performance was evaluated in nude mice bearing SKOV3 tumors using PET imaging, biodistribution analysis, and metabolic stability studies.","limitations":"This is a preclinical mouse study using human tumor cells implanted under the skin, which doesn't fully represent how cancers grow in humans. The xenograft model lacks a functioning immune system. The study did not test the probes in larger animals or humans. Kidney uptake of small peptides can be high and was not extensively discussed. Long-term toxicity of the probes was not assessed."},{"rthcId":"RPEP-04434","title":"Gelatin and Antioxidant Peptides from Gelatin Hydrolysate of Skipjack Tuna (Katsuwonus pelamis) Scales: Preparation, Identification and Activity Evaluation.","authors":"Qiu, Yi-Ting; Wang, Yu-Mei; Yang, Xiu-Rong; Zhao, Yu-Qin; Chi, Chang-Feng; Wang, Bin","year":2019,"journal":"Marine drugs, 17(10)","doi":"10.3390/md17100565","pmid":"31623339","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04435","title":"Effective mRNA pulmonary delivery by dry powder formulation of PEGylated synthetic KL4 peptide.","authors":"Qiu, Yingshan; Man, Rico C H; Liao, Qiuying; Kung, Keshia L K; Chow, Michael Y T; Lam, Jenny K W","year":2019,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 314, 102-115","doi":"10.1016/j.jconrel.2019.10.026","pmid":"31629037","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04436","title":"Staphylococcus epidermidis Activates Aryl Hydrocarbon Receptor Signaling in Human Keratinocytes: Implications for Cutaneous Defense.","authors":"Rademacher, Franziska; Simanski, Maren; Hesse, Bettina; Dombrowsky, Gregor; Vent, Nikolas; Gläser, Regine; Harder, Jürgen","year":2019,"journal":"Journal of innate immunity, 11(2), 125-135","doi":"10.1159/000492162","pmid":"30176668","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04437","title":"Bombesin conjugated solid lipid nanoparticles for improved delivery of epigallocatechin gallate for breast cancer treatment.","authors":"Radhakrishnan, Rasika; Pooja, Deep; Kulhari, Hitesh; Gudem, Sagarika; Ravuri, Halley Gora; Bhargava, Suresh; Ramakrishna, Sistla","year":2019,"journal":"Chemistry and physics of lipids, 224, 104770","doi":"10.1016/j.chemphyslip.2019.04.005","pmid":"30965023","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"EGCG was successfully encapsulated in solid lipid nanoparticles (SLNs) and conjugated with bombesin, a peptide that targets gastrin-releasing peptide receptors (GRPR) overexpressed on breast cancer cells. In vitro, the bombesin-conjugated formulation showed greater cytotoxicity to cancer cell lines compared to non-conjugated nanoparticles.\n\nIn vivo experiments in C57/BL6 mice with breast tumors demonstrated that the peptide-conjugated formulation produced greater tumor volume reduction and improved survival compared to both non-conjugated nanoparticles and plain EGCG. The results demonstrate that peptide-mediated targeting significantly enhances the therapeutic efficacy of EGCG delivery for breast cancer.","whyItMatters":"EGCG has well-documented anticancer properties but is limited by poor stability and bioavailability in the body. Using a peptide like bombesin to guide drug-loaded nanoparticles directly to tumor cells is a strategy that could dramatically improve the therapeutic index of natural anticancer compounds — delivering more drug to the tumor while reducing off-target effects.","specificNumbers":"","methodology":"The researchers prepared solid lipid nanoparticles loaded with EGCG using standard nanoparticle fabrication techniques. Bombesin peptide was conjugated to the nanoparticle surface to enable targeting of GRPR-overexpressing cancer cells. In vitro cytotoxicity was assessed on cancer cell lines. In vivo efficacy was evaluated in C57/BL6 mice bearing breast tumors, measuring tumor volume and survival over the treatment period.","limitations":"The study used a single mouse strain and breast tumor model, which may not capture the diversity of human breast cancers. Specific tumor volume measurements and survival data were not provided in the abstract. The pharmacokinetics, biodistribution, and long-term safety of the bombesin-conjugated nanoparticles were not detailed. EGCG doses used in nanoparticle form may not directly translate to human therapeutic doses."},{"rthcId":"RPEP-04438","title":"Supramolecular Nanofibrous Peptide/Polymer Hydrogels for the Multiplexing of Bioactive Signals.","authors":"Radvar, Elham; Azevedo, Helena S","year":2019,"journal":"ACS biomaterials science & engineering, 5(9), 4646-4656","doi":"10.1021/acsbiomaterials.9b00941","pmid":"33448837","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Combining a positively charged peptide amphiphile (PA) with the negatively charged synthetic polymer PSS created hybrid hydrogels through supramolecular self-assembly. These PSS/PA hydrogels exhibited high mechanical stiffness, stability in buffered environments, and a nanofibrous structure resembling natural extracellular matrix.\n\nThe hydrogels could retain and sustainably release proteins of different charges — useful for controlled growth factor delivery. The sulfonate groups in PSS promoted controllable mineralization in osteogenic conditions. Human mesenchymal stem cells encapsulated in the hydrogels remained viable, demonstrating biocompatibility and potential for stem cell-based tissue engineering.","whyItMatters":"Tissue engineering needs scaffolds that can deliver multiple biological signals simultaneously — growth factors for differentiation, structural cues for organization, and mineral scaffolds for bone formation. This peptide-polymer hybrid achieves all three in a single material. The ability to multiplex bioactive signals in one scaffold could simplify tissue engineering protocols and bring regenerative medicine closer to creating complex, functional tissues.","specificNumbers":"High mechanical stiffness · Stable in buffer · Controlled mineralization · Sustained protein release · Human mesenchymal stem cells viable","methodology":"Researchers fabricated hybrid hydrogels by combining positively charged peptide amphiphiles with negatively charged PSS polymer. Mechanical properties were measured by rheology. Mineralization was induced in osteogenic medium and characterized. Protein loading and release was tested with differently charged model proteins. Human mesenchymal stem cell viability was assessed after encapsulation in the hydrogels.","limitations":"The study demonstrates proof-of-concept without showing actual stem cell differentiation into specific tissue types. Only cell viability, not functional tissue formation, was assessed. In vivo testing was not performed. The specific growth factors that could be delivered were not tested — only model proteins. Long-term degradation behavior and immune response remain uncharacterized."},{"rthcId":"RPEP-04439","title":"Monoclonal antibodies for the prevention of migraine.","authors":"Raffaelli, Bianca; Neeb, Lars; Reuter, Uwe","year":2019,"journal":"Expert opinion on biological therapy, 19(12), 1307-1317","doi":"10.1080/14712598.2019.1671350","pmid":"31550937","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04440","title":"Lipids and insulin regulate mitochondrial-derived peptide (MOTS-c) in PCOS and healthy subjects.","authors":"Ramanjaneya, Manjunath; Jerobin, Jayakumar; Bettahi, Ilham; Bensila, Milin; Aye, Myint; Siveen, Kodappully Sivaraman; Sathyapalan, Thozhukat; Skarulis, Monica; Abou-Samra, Abdul-Badi; Atkin, Stephen L","year":2019,"journal":"Clinical endocrinology, 91(2), 278-287","doi":"10.1111/cen.14007","pmid":"31066084","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04441","title":"Differential functional selectivity and downstream signaling bias of ghrelin receptor antagonists and inverse agonists.","authors":"Ramirez, Valerie T; van Oeffelen, Wesley E P A; Torres-Fuentes, Cristina; Chruścicka, Barbara; Druelle, Clementine; Golubeva, Anna V; van de Wouw, Marcel; Dinan, Timothy G; Cryan, John F; Schellekens, Harriët","year":2019,"journal":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 33(1), 518-531","doi":"10.1096/fj.201800655R","pmid":"30020830","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04442","title":"Peptide-based therapeutics: quality specifications, regulatory considerations, and prospects.","authors":"Rastogi, Shruti; Shukla, Shatrunajay; Kalaivani, M; Singh, Gyanendra Nath","year":2019,"journal":"Drug discovery today, 24(1), 148-162","doi":"10.1016/j.drudis.2018.10.002","pmid":"30296551","tags":[],"studyType":"review","evidenceStrength":"moderate","keyFinding":"The global regulatory landscape for peptide-based therapeutics (PbTs) suffers from a significant lack of harmonization. Different pharmacopoeias (the official standards books used by regulators in different countries) use different test methods, specifications, and quality standards for the same peptide drugs. This inconsistency creates barriers for the global pharmaceutical industry and could slow the adoption of new peptide therapeutics.\n\nThe review identifies peptides' core advantages — high selectivity, strong efficacy, and low toxicity — as driving increased industry investment. However, the authors argue that standardizing quality specifications and test methods across international pharmacopoeias would further accelerate peptide drug development and global market access.","whyItMatters":"The peptide therapeutics market has been growing rapidly, but regulatory complexity remains a major barrier. When different countries apply different quality standards to the same peptide drug, manufacturers face increased costs, delayed approvals, and market fragmentation. Harmonizing these standards would make it easier and cheaper to bring peptide drugs to patients worldwide — particularly important as the pipeline of peptide therapeutics continues to expand.","specificNumbers":"Multiple pharmacopoeias compared · Lack of harmonization across test procedures identified · Peptide selectivity, efficacy, and minimal toxicity highlighted as advantages · Global pharmaceutical industry interest increasing","methodology":"The authors conducted a comparative review of pharmacopoeial standards for peptide-based therapeutics across major international pharmacopoeias. They analyzed test procedures, specifications, and monographs to identify commonalities and differences, focusing on quality control methodologies for peptide active pharmaceutical ingredients.","limitations":"This is a regulatory landscape review rather than a clinical study, so it doesn't assess therapeutic efficacy or safety. The analysis focuses on published pharmacopoeial standards and may not capture internal regulatory policies or recent updates. The review was published in 2019, and regulatory frameworks continue to evolve. Specific pharmacopoeial editions analyzed may have been updated since."},{"rthcId":"RPEP-04443","title":"Selective Targeting of Integrin αvβ8 by a Highly Active Cyclic Peptide.","authors":"Reichart, Florian; Maltsev, Oleg V; Kapp, Tobias G; Räder, Andreas F B; Weinmüller, Michael; Marelli, Udaya Kiran; Notni, Johannes; Wurzer, Alexander; Beck, Roswitha; Wester, Hans-Jürgen; Steiger, Katja; Di Maro, Salvatore; Di Leva, Francesco Saverio; Marinelli, Luciana; Nieberler, Markus; Reuning, Ute; Schwaiger, Markus; Kessler, Horst","year":2019,"journal":"Journal of medicinal chemistry, 62(4), 2024-2037","doi":"10.1021/acs.jmedchem.8b01588","pmid":"30657681","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04444","title":"The role of molecular simulations in understanding the mechanisms of cell-penetrating peptides.","authors":"Reid, Lauren M; Verma, Chandra S; Essex, Jonathan W","year":2019,"journal":"Drug discovery today, 24(9), 1821-1835","doi":"10.1016/j.drudis.2019.06.013","pmid":"31229665","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04445","title":"Histopathological analysis of the synovium in trapeziometacarpal osteoarthritis.","authors":"Rein, Susanne; Okogbaa, Janet; Hagert, Elisabet; Manthey, Suzanne; Ladd, Amy","year":2019,"journal":"The Journal of hand surgery, European volume, 44(10), 1079-1088","doi":"10.1177/1753193419848600","pmid":"31109229","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04446","title":"Thymosin β4 promotes autophagy and repair via HIF-1α stabilization in chronic granulomatous disease.","authors":"Renga, Giorgia; Oikonomou, Vasilis; Moretti, Silvia; Stincardini, Claudia; Bellet, Marina M; Pariano, Marilena; Bartoli, Andrea; Brancorsini, Stefano; Mosci, Paolo; Finocchi, Andrea; Rossi, Paolo; Costantini, Claudio; Garaci, Enrico; Goldstein, Allan L; Romani, Luigina","year":2019,"journal":"Life science alliance, 2(6)","doi":"10.26508/lsa.201900432","pmid":"31719116","tags":[],"studyType":"in vitro + animal study","evidenceStrength":"low","keyFinding":"Thymosin β4 (Tβ4), a naturally occurring peptide known for roles in wound healing and tissue repair, promoted a specialized form of autophagy (noncanonical autophagy) in both human and mouse cells from chronic granulomatous disease (CGD) — a genetic immune disorder. The peptide worked by stabilizing HIF-1α, a protein that was abnormally low in CGD cells, which in turn activated autophagy and genes that protect mucosal barriers. In CGD mice with either colitis or aspergillosis (a fungal infection), Tβ4 treatment reduced inflammation, decreased granuloma formation, and improved survival. The study establishes Tβ4 as a potential therapeutic for CGD through a specific, druggable pathway.","whyItMatters":"Chronic granulomatous disease is a rare but serious genetic condition where patients' immune cells can't properly kill certain bacteria and fungi, leading to recurrent severe infections and excessive inflammation. Current treatments are limited — mainly antibiotics, antifungals, and bone marrow transplant. Thymosin β4 represents a fundamentally different approach: rather than fighting pathogens directly, it restores the body's own inflammation-resolution pathways. The identification of the HIF-1α mechanism provides a clear molecular target for future drug development.","specificNumbers":"Tβ4 normalized HIF-1α expression · Promoted noncanonical autophagy via DAPK1 · Reduced inflammation and granulomas · Improved survival in CGD mice with colitis and aspergillosis","methodology":"Researchers studied thymosin β4 effects in human CGD cells and murine CGD models. They characterized the autophagy pathway (noncanonical, mediated by death-associated protein kinase 1/DAPK1), measured HIF-1α expression in CGD versus normal cells, and tested whether Tβ4 could normalize it. In vivo experiments used CGD mice with either colitis or aspergillosis, assessing inflammation, granuloma formation, and survival with Tβ4 treatment or direct HIF-1α stabilization.","limitations":"This is preclinical research — CGD mouse models may not perfectly replicate human CGD. The study doesn't address optimal dosing, route of administration, or long-term safety in the context of CGD. Thymosin β4's pleiotropic nature (it affects many cellular processes) means unintended effects are possible. No human trials for CGD with Tβ4 have been conducted. CGD is rare, making large clinical trials challenging to design."},{"rthcId":"RPEP-04447","title":"Bioactive peptides and proteins as alternative antiplatelet drugs.","authors":"Rengasamy, Kannan R R; Khan, Haroon; Ahmad, Imad; Lobine, Devina; Mahomoodally, Fawzi; Suroowan, Shanoo; Hassan, Sherif T S; Xu, Suowen; Patel, Seema; Daglia, Maria; Nabavi, Seyed Mohammad; Pandian, Shunmugiah Karutha","year":2019,"journal":"Medicinal research reviews, 39(6), 2153-2171","doi":"10.1002/med.21579","pmid":"31006878","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04448","title":"Best practices for bioinformatic characterization of neoantigens for clinical utility.","authors":"Richters, Megan M; Xia, Huiming; Campbell, Katie M; Gillanders, William E; Griffith, Obi L; Griffith, Malachi","year":2019,"journal":"Genome medicine, 11(1), 56","doi":"10.1186/s13073-019-0666-2","pmid":"31462330","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The neoantigen prediction workflow involves multiple computational steps: somatic mutation identification from tumor-normal sequencing, HLA typing to determine the patient's immune molecule profile, peptide processing prediction, and peptide-MHC binding prediction. The authors provide specific recommendations for each step and identify key areas needing improvement, including HLA class II typing accuracy, software support for diverse neoantigen sources beyond point mutations, and incorporation of clinical response data to improve prediction algorithms. Currently, there is no consensus approach, and the field needs standardization.","whyItMatters":"Personalized cancer vaccines are one of the most promising frontiers in oncology. The success of these vaccines depends entirely on correctly identifying which peptide neoantigens to include. This guide helps researchers and clinicians avoid common pitfalls and apply best practices, potentially improving vaccine efficacy and patient outcomes.","specificNumbers":"","methodology":"This is a comprehensive review and best-practices guide that evaluates computational tools and analysis workflows for neoantigen characterization. The authors reviewed the literature on neoantigen prediction, prioritization, delivery, and validation, synthesizing findings from multiple preclinical and clinical trials to provide practical guidance for clinical implementation.","limitations":"As a review and best-practices guide, no new experimental data is presented. The field is evolving rapidly, and some recommendations may be superseded by newer tools and algorithms. Prediction accuracy for neoantigen immunogenicity remains imperfect — not all predicted neoantigens actually trigger immune responses. HLA class II prediction is notably less accurate than class I."},{"rthcId":"RPEP-04449","title":"Randomized controlled trial on a PRP-like cosmetic, biomimetic peptides based, for the treatment of alopecia areata.","authors":"Rinaldi, Fabio; Marzani, Barbara; Pinto, Daniela; Sorbellini, Elisabetta","year":2019,"journal":"The Journal of dermatological treatment, 30(6), 588-593","doi":"10.1080/09546634.2018.1544405","pmid":"30513014","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04450","title":"Early Phase of Type 1 Diabetes Decreases the Responsiveness of C-Fiber Nociceptors in the Temporomandibular Joint of Rats.","authors":"Rocha-Neto, Luiz M; Gamarra-Suárez, Jaime R; Freitas, Fabiana F; Muzilli, Augusto; Abdalla, Henrique B; Macedo, Cristina G; Napimoga, Marcelo H; Clemente-Napimoga, Juliana T","year":2019,"journal":"Neuroscience, 416, 229-238","doi":"10.1016/j.neuroscience.2019.08.011","pmid":"31404587","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In streptozotocin-induced type 1 diabetic rats, C-fiber nociceptors in the temporomandibular joint became hyporesponsive starting from day 7 after disease induction. This was associated with significantly reduced protein levels of the neuropeptides substance P and calcitonin gene-related peptide (CGRP).\n\nParadoxically, while pain sensing decreased, inflammatory markers increased — higher levels of pro-inflammatory cytokine IL-1β and chemokine CINC-1/CXCL-1 were observed. PKC-α/β inhibitor (GO6976) or PKC-β inhibitor (LY333531) treatment restored capsaicin-induced nociception and increased Na+/K+-ATPase pump levels in the trigeminal ganglia.\n\nThe overall picture suggests diabetes creates a condition where tissue-damaging inflammation proceeds without pain perception, potentially leading to undetected joint degeneration.","whyItMatters":"Diabetic patients frequently develop neuropathy where they lose pain sensation while tissue damage continues unchecked — this is why diabetic foot ulcers become so severe. This study shows the same dangerous pattern occurs in the jaw joint, driven by neuropeptide depletion, and identifies PKC signaling as a potential target to restore protective pain sensing.","specificNumbers":"","methodology":"Wistar rats received streptozotocin (75 mg/kg) to induce type 1 diabetes. TMJ nociception was assessed using capsaicin and formalin challenges. Neuropeptide levels (substance P, CGRP), inflammatory markers (IL-1β, CINC-1/CXCL-1), and Na+/K+-ATPase pump protein levels were measured in the trigeminal ganglia. PKC inhibitors were used to investigate the signaling mechanism underlying nociceptor hyporesponsiveness.","limitations":"This is an animal study using streptozotocin-induced diabetes, which models type 1 diabetes and may not fully represent the slower-onset type 2 diabetes. The TMJ findings may not translate directly to other joints. Only early-phase diabetes was studied; long-term effects were not examined. The specific mechanisms linking diabetes to neuropeptide reduction need further investigation."},{"rthcId":"RPEP-04451","title":"Novel approaches to anti-obesity drug discovery with gut hormones over the past 10 years.","authors":"Rose, Frances; Bloom, Stephen; Tan, Tricia","year":2019,"journal":"Expert opinion on drug discovery, 14(11), 1151-1159","doi":"10.1080/17460441.2019.1646243","pmid":"31355685","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04452","title":"Central Nervous System and Peripheral Hormone Responses to a Meal in Children.","authors":"Roth, Christian L; Melhorn, Susan J; Elfers, Clinton T; Scholz, Kelley; De Leon, Mary Rosalynn B; Rowland, Maya; Kearns, Sue; Aylward, Elizabeth; Grabowski, Thomas J; Saelens, Brian E; Schur, Ellen A","year":2019,"journal":"The Journal of clinical endocrinology and metabolism, 104(5), 1471-1483","doi":"10.1210/jc.2018-01525","pmid":"30418574","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04453","title":"Comparison of Anti-Viral Activity of Frog Skin Anti-Microbial Peptides Temporin-Sha and [K³]SHa to LL-37 and Temporin-Tb against Herpes Simplex Virus Type 1.","authors":"Roy, Maëva; Lebeau, Lucie; Chessa, Céline; Damour, Alexia; Ladram, Ali; Oury, Bruno; Boutolleau, David; Bodet, Charles; Lévêque, Nicolas","year":2019,"journal":"Viruses, 11(1)","doi":"10.3390/v11010077","pmid":"30669255","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04454","title":"Arcuate Kisspeptin Neurons Coordinate Reproductive Activities with Metabolism.","authors":"Rønnekleiv, Oline K; Qiu, Jian; Kelly, Martin J","year":2019,"journal":"Seminars in reproductive medicine, 37(3), 131-140","doi":"10.1055/s-0039-3400251","pmid":"31869841","tags":["kisspeptin","reproductive-hormones","metabolism"],"studyType":"Review","evidenceStrength":"Moderate","keyFinding":"Arcuate kisspeptin neurons serve as the critical link between your body's energy status and its reproductive system. These neurons are now recognized as the \"command neurons\" that drive the pulsatile release of GnRH — the master reproductive hormone. Crucially, kisspeptin neurons express receptors for metabolic hormones like insulin and leptin, meaning they can directly sense the body's energy reserves.\n\nThis dual role explains a long-standing mystery: how does the brain know to shut down fertility when energy is scarce? GnRH neurons themselves lack receptors for most metabolic hormones, so they can't sense energy status directly. Kisspeptin neurons bridge this gap — they respond to insulin and leptin (similar to POMC neurons), and they have direct synaptic connections to both GnRH neurons and the POMC/NPY-AgRP appetite circuits, making them a central coordinator of reproduction and metabolism.","whyItMatters":"This review reframes kisspeptin from a purely reproductive peptide into a metabolic integrator. Understanding that kisspeptin neurons sit at the intersection of fertility and energy balance has major implications for conditions like PCOS, hypothalamic amenorrhea (when women stop menstruating due to low body weight or stress), and obesity-related infertility. It also explains why extreme dieting or metabolic disorders can shut down the reproductive system.","specificNumbers":"Not applicable (narrative review synthesizing neuroscience research)","methodology":"This is a narrative review published in Seminars in Reproductive Medicine that synthesizes research on arcuate kisspeptin neuron physiology, their synaptic connections with GnRH, POMC, and NPY/AgRP neurons, and their responses to metabolic hormones including insulin, leptin, and estradiol.","limitations":"As a narrative review, it presents a synthesis of existing research rather than new experimental data. Much of the mechanistic understanding comes from animal models (primarily rodent), and translation to human physiology requires caution. The review focuses specifically on arcuate kisspeptin neurons and may not fully capture the role of kisspeptin neurons in other brain regions."},{"rthcId":"RPEP-04455","title":"European headache federation guideline on the use of monoclonal antibodies acting on the calcitonin gene related peptide or its receptor for migraine prevention.","authors":"Sacco, Simona; Bendtsen, Lars; Ashina, Messoud; Reuter, Uwe; Terwindt, Gisela; Mitsikostas, Dimos-Dimitrios; Martelletti, Paolo","year":2019,"journal":"The journal of headache and pain, 20(1), 6","doi":"10.1186/s10194-018-0955-y","pmid":"30651064","tags":["cgrp"],"studyType":"guideline","evidenceStrength":"strong","keyFinding":"The European Headache Federation formally recommends all four anti-CGRP monoclonal antibodies for migraine prevention. For episodic migraine, eptinezumab, erenumab, fremanezumab, and galcanezumab are recommended based on low to high quality evidence. For chronic migraine, erenumab, fremanezumab, and galcanezumab are recommended based on medium to high quality evidence.\n\nOne antibody (erenumab) targets the CGRP receptor, while the other three (eptinezumab, fremanezumab, galcanezumab) target the CGRP peptide itself. The guideline notes that for many clinical questions — like which patients to prioritize, when to switch between drugs, or how long to treat — evidence was insufficient and recommendations relied on expert opinion.","whyItMatters":"This was the first official European guideline for anti-CGRP monoclonal antibodies in migraine, establishing them as evidence-based preventive treatments. CGRP is a peptide that plays a central role in migraine pathophysiology, and these antibodies represented the first migraine-specific preventive therapy class. The guideline gave clinicians an evidence-based framework for prescribing these drugs, which have since become a standard of care for patients who don't respond to traditional preventives.","specificNumbers":"4 monoclonal antibodies evaluated · Low–high quality evidence for episodic migraine · Medium–high quality evidence for chronic migraine · 1 targets CGRP receptor (erenumab) · 3 target CGRP peptide (eptinezumab, fremanezumab, galcanezumab)","methodology":"The guideline was developed using the GRADE (Grading of Recommendation, Assessment, Development, and Evaluation) approach. The working group performed systematic literature review, assessed evidence quality, and formulated recommendations. Where evidence was insufficient for GRADE-based recommendations, expert opinion was used.","limitations":"Published in 2019, this guideline reflects early-stage evidence for these drugs — long-term safety and real-world effectiveness data were limited at the time. Several clinical questions (patient selection, switching between drugs, treatment duration) lacked sufficient evidence for formal recommendations. The guideline has likely been updated or supplemented since publication."},{"rthcId":"RPEP-04456","title":"Pain therapeutics from cone snail venoms: From Ziconotide to novel non-opioid pathways.","authors":"Safavi-Hemami, Helena; Brogan, Shane E; Olivera, Baldomero M","year":2019,"journal":"Journal of proteomics, 190, 12-20","doi":"10.1016/j.jprot.2018.05.009","pmid":"29777871","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04457","title":"Formulation Composition and Process Affect Counterion for CSP7 Peptide.","authors":"Sahakijpijarn, Sawittree; Moon, Chaeho; Koleng, John J; Williams, Robert O","year":2019,"journal":"Pharmaceutics, 11(10)","doi":"10.3390/pharmaceutics11100498","pmid":"31569515","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The pH modifier excipient had the greatest impact on counterion loss during lyophilization of CSP7 peptide formulations. Optimizing the molar ratio of bulking agent to CSP7 preserved volatile compounds after lyophilization.\n\nHigher chamber pressure during lyophilization lowered the sublimation rate of volatile compounds, helping retain counterions. Loss of volatile counterions caused pH shifts in reconstituted solutions, which in turn triggered peptide aggregation and reduced stability. Different salt forms of CSP7 (acetate vs. trifluoroacetate counterions) affected counterion volatilization differently. The study demonstrates that both formulation composition and processing parameters must be optimized together to maintain peptide drug stability.","whyItMatters":"Peptide drugs are a rapidly growing drug class, but their formulation is challenging due to instability issues. This study addresses a specific but critical problem: how counterions lost during manufacturing can destabilize the final product. The practical insights — which excipients to use, how to optimize ratios, and what processing conditions to maintain — are directly applicable to developing stable peptide drug products across the pharmaceutical industry.","specificNumbers":"","methodology":"Researchers prepared various lyophilized formulations of CSP7 peptide with different excipients and salt forms. They used 1H and 19F NMR spectroscopy to calculate molar ratios of counterions to CSP7 before and after lyophilization. The effects of excipient types, bulking agent ratios, and lyophilization chamber pressure on counterion preservation were systematically evaluated. Peptide stability and aggregation were assessed in reconstituted solutions.","limitations":"The study focused on a single peptide (CSP7), and results may not directly apply to all peptide drugs due to differences in physicochemical properties. The investigation was conducted at laboratory scale; scale-up to manufacturing may introduce additional variables. Only lyophilization was studied; other drying methods were not compared. Long-term stability under various storage conditions was not fully assessed. The counterion effects may differ for peptides with different charge profiles."},{"rthcId":"RPEP-04458","title":"Collaborative membrane activity and receptor-dependent tumor cell targeting for precise nanoparticle delivery in CXCR4+ colorectal cancer.","authors":"Sala, Rita; Sánchez-García, Laura; Serna, Naroa; Céspedes, María Virtudes; Casanova, Isolda; Roldán, Mònica; Sánchez-Chardi, Alejandro; Unzueta, Ugutz; Vázquez, Esther; Mangues, Ramón; Villaverde, Antonio","year":2019,"journal":"Acta biomaterialia, 99, 426-432","doi":"10.1016/j.actbio.2019.09.002","pmid":"31494293","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04459","title":"Optimizing Lysosomal Activation of Antibody-Drug Conjugates (ADCs) by Incorporation of Novel Cleavable Dipeptide Linkers.","authors":"Salomon, Paulin L; Reid, Emily E; Archer, Katie E; Harris, Luke; Maloney, Erin K; Wilhelm, Alan J; Miller, Michael L; Chari, Ravi V J; Keating, Thomas A; Singh, Rajeeva","year":2019,"journal":"Molecular pharmaceutics, 16(12), 4817-4825","doi":"10.1021/acs.molpharmaceut.9b00696","pmid":"31609629","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04460","title":"Keratinocyte infection by Actinomadura madurae triggers an inflammatory response.","authors":"Santiago-Téllez, Alfonso; Castrillón-Rivera, Laura Estela; Palma-Ramos, Alejandro; Bello-López, Juan Manuel; Sainz-Espuñes, Teresita; Contreras-Paredes, Adriana; Luna-Herrera, Julieta; Castañeda-Sánchez, Jorge Ismael","year":2019,"journal":"Transactions of the Royal Society of Tropical Medicine and Hygiene, 113(7), 392-398","doi":"10.1093/trstmh/trz022","pmid":"30989203","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A. madurae achieved intracellular replication in HaCaT keratinocytes early in infection, but the cells eventually controlled the bacterial growth. In response to infection, keratinocytes overexpressed Toll-like receptors TLR2 and TLR6, and produced high concentrations of the antimicrobial peptides LL-37, human beta-defensin-1 (hBD-1), and human beta-defensin-2 (hBD-2).\n\nThe infected cells also released inflammatory chemokines and cytokines including monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8), which recruit immune cells to the infection site. Tumor necrosis factor alpha (TNFα) was produced at lower levels. These findings demonstrate that keratinocytes are active participants in the immune defense against actinomycetoma, not just passive barriers.","whyItMatters":"Actinomycetoma is a neglected tropical disease that causes chronic, disfiguring skin infections primarily affecting people in developing countries. Understanding how the body's first line of defense — skin cells — responds to this infection could inform new treatment strategies. The finding that keratinocytes produce multiple antimicrobial peptides against A. madurae suggests these natural peptides could potentially be harnessed or boosted as therapeutic agents.","specificNumbers":"","methodology":"HaCaT keratinocyte cell lines were infected with A. madurae at a multiplicity of infection of 20:1 for 2 hours. Samples were collected from 2 to 72 hours post-infection. Intracellular bacterial replication was measured by colony-forming unit counts. TLR expression and antimicrobial peptide production were assessed by confocal microscopy. Chemokine and cytokine levels were quantified by ELISA.","limitations":"This is an in vitro study using a single keratinocyte cell line (HaCaT), which may not fully represent the complex immune environment of living skin tissue with its multiple cell types and systemic immune connections. The study tested only one bacterial strain at one multiplicity of infection. Whether the antimicrobial peptides produced are sufficient to control infection in vivo remains unclear."},{"rthcId":"RPEP-04461","title":"Antibacterial Activity of Plant Defensins.","authors":"Sathoff, Andrew E; Samac, Deborah A","year":2019,"journal":"Molecular plant-microbe interactions : MPMI, 32(5), 507-514","doi":"10.1094/MPMI-08-18-0229-CR","pmid":"30501455","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04462","title":"Pharmacological Modulation of Ghrelin to Induce Weight Loss: Successes and Challenges.","authors":"Schalla, Martha A; Stengel, Andreas","year":2019,"journal":"Current diabetes reports, 19(10), 102","doi":"10.1007/s11892-019-1211-9","pmid":"31506846","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04463","title":"Actions and Potential Therapeutic Applications of Growth Hormone-Releasing Hormone Agonists.","authors":"Schally, Andrew V; Zhang, Xianyang; Cai, Renzhi; Hare, Joshua M; Granata, Riccarda; Bartoli, Manuela","year":2019,"journal":"Endocrinology, 160(7), 1600-1612","doi":"10.1210/en.2019-00111","pmid":"31070727","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GHRH agonists of the JI and MR class demonstrated broad therapeutic potential across multiple organ systems in preclinical studies. MR-409 improved pancreatic β-cell proliferation and metabolic function, and facilitated islet engraftment after transplantation in rodents, offering a new approach to diabetes treatment.\n\nIn cardiac models, GHRH agonists improved ejection fraction and reduced infarct size in rats, reduced infarct scar in swine, and attenuated cardiac hypertrophy in mice. Notably, while GHRH agonists stimulated cancer cell growth in vitro, they inhibited tumor growth in vivo in xenograft models and downregulated GHRH receptors, suggesting a complex but potentially beneficial relationship with cancer biology.","whyItMatters":"GHRH agonists represent a class of peptide therapeutics with unusually broad potential applications. Rather than being limited to growth hormone disorders, these peptides interact with GHRH receptors found throughout the body, opening up treatment possibilities for diabetes, heart disease, eye disease, and wound healing. The paradoxical finding that they inhibit tumors in living animals despite stimulating cancer cells in lab dishes adds an intriguing dimension to their safety and therapeutic profile.","specificNumbers":"","methodology":"This is a narrative review article summarizing the authors' own body of research and related literature on GHRH agonists. The review covers the synthesis and biological evaluation of potent GHRH agonists (JI and MR class), drawing on preclinical studies in rodents and swine models across multiple disease areas including diabetes, cardiac injury, retinopathy, and cancer.","limitations":"The therapeutic effects described are almost entirely from preclinical animal studies (rodents and swine), with no human clinical trial data presented. The paradoxical in vitro vs. in vivo cancer findings are not fully explained mechanistically. As a review from the group that developed many of these agonists, there may be selection bias toward favorable results. Translation from animal models to human therapies remains uncertain."},{"rthcId":"RPEP-04464","title":"Cathelicidins PMAP-36, LL-37 and CATH-2 are similar peptides with different modes of action.","authors":"Scheenstra, Maaike R; van den Belt, Matthias; Tjeerdsma-van Bokhoven, Johanna L M; Schneider, Viktoria A F; Ordonez, Soledad R; van Dijk, Albert; Veldhuizen, Edwin J A; Haagsman, Henk P","year":2019,"journal":"Scientific reports, 9(1), 4780","doi":"10.1038/s41598-019-41246-6","pmid":"30886247","tags":[],"studyType":"in-vitro-study","evidenceStrength":"preliminary","keyFinding":"Three cathelicidin antimicrobial peptides from different species — pig (PMAP-36), human (LL-37), and chicken (CATH-2) — kill E. coli bacteria through fundamentally different mechanisms despite being structurally similar peptides. Transmission electron microscopy revealed distinct killing patterns for each peptide.\n\nSurprisingly, LL-37 binds bacterial endotoxin (LPS) very weakly compared to PMAP-36, yet it was the most potent at blocking LPS activation of immune cells (macrophages). This means strong LPS binding doesn't necessarily predict strong immunomodulatory activity.\n\nStructure-activity analysis of PMAP-36 revealed that the first 11 amino acids at the N-terminal end could be removed without affecting bacterial killing, LPS neutralization, or binding. Cutting 4 more amino acids, however, dramatically reduced all activities. Shorter PMAP-36 analogs required dimerization (pairing up) for immunomodulatory function but not for bacterial killing — indicating these are separable activities.","whyItMatters":"As antibiotic resistance grows, host defense peptides (cathelicidins) are being studied as potential alternatives. This research matters because it shows that similar-looking antimicrobial peptides can work through completely different mechanisms — meaning scientists can't simply assume one cathelicidin will behave like another. The finding that antibacterial and immunomodulatory activities can be separated opens the door to engineering peptides optimized for specific therapeutic goals.","specificNumbers":"3 cathelicidins compared · E. coli killing model · First 11 amino acids dispensable for PMAP-36 activity · Dimerization required for short analogs' immunomodulation · LPS binding ≠ LPS neutralization capacity","methodology":"Researchers compared three cathelicidins (pig PMAP-36, human LL-37, chicken CATH-2) and several PMAP-36 truncation analogs using multiple in vitro assays. Transmission electron microscopy visualized bacterial killing mechanisms. LPS binding and neutralization were measured separately. Macrophage activation assays (using RAW 264.7 cells) assessed immunomodulatory capacity. Monomer vs dimer forms of the peptides were tested to determine which structural form was needed for each function.","limitations":"This is entirely an in vitro study — effects in a test tube may differ from what happens inside a living organism. Only E. coli was tested as a target bacterium; activity against other pathogens may differ. The immunomodulatory assays used a mouse macrophage cell line (RAW 264.7), which may not perfectly reflect human immune responses."},{"rthcId":"RPEP-04465","title":"Inhibition of experimental visceral pain in rodents by cebranopadol.","authors":"Schiene, Klaus; Schröder, Wolfgang; Linz, Klaus; Frosch, Stefanie; Tzschentke, Thomas M; Christoph, Thomas; Xie, Jennifer Y; Porreca, Frank","year":2019,"journal":"Behavioural pharmacology, 30(4), 320-326","doi":"10.1097/FBP.0000000000000420","pmid":"30161034","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04466","title":"Mutational landscape of the transcriptome offers putative targets for immunotherapy of myeloproliferative neoplasms.","authors":"Schischlik, Fiorella; Jäger, Roland; Rosebrock, Felix; Hug, Eva; Schuster, Michael; Holly, Raimund; Fuchs, Elisabeth; Milosevic Feenstra, Jelena D; Bogner, Edith; Gisslinger, Bettina; Schalling, Martin; Rumi, Elisa; Pietra, Daniela; Fischer, Gottfried; Faé, Ingrid; Vulliard, Loan; Menche, Jörg; Haferlach, Torsten; Meggendorfer, Manja; Stengel, Anna; Bock, Christoph; Cazzola, Mario; Gisslinger, Heinz; Kralovics, Robert","year":2019,"journal":"Blood, 134(2), 199-210","doi":"10.1182/blood.2019000519","pmid":"31064751","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04467","title":"Targeted Subcellular Protein Delivery Using Cleavable Cyclic Cell-Penetrating Peptides.","authors":"Schneider, Anselm F L; Wallabregue, Antoine L D; Franz, Luise; Hackenberger, Christian P R","year":2019,"journal":"Bioconjugate chemistry, 30(2), 400-404","doi":"10.1021/acs.bioconjchem.8b00855","pmid":"30616339","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04468","title":"New Trends in Migraine Pharmacology: Targeting Calcitonin Gene-Related Peptide (CGRP) With Monoclonal Antibodies.","authors":"Scuteri, Damiana; Adornetto, Annagrazia; Rombolà, Laura; Naturale, Maria Diana; Morrone, Luigi Antonio; Bagetta, Giacinto; Tonin, Paolo; Corasaniti, Maria Tiziana","year":2019,"journal":"Frontiers in pharmacology, 10, 363","doi":"10.3389/fphar.2019.00363","pmid":"31024319","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04469","title":"Polymorphisms in the P2X7 receptor, and differential expression of Toll-like receptor-mediated cytokines and defensins, in a Canadian Indigenous group.","authors":"Semple, Catlin; Choi, Ka-Yee Grace; Kroeker, Andrea; Denechezhe, Lizette; Orr, Pamela; Mookherjee, Neeloffer; Larcombe, Linda","year":2019,"journal":"Scientific reports, 9(1), 14204","doi":"10.1038/s41598-019-50596-0","pmid":"31578370","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04470","title":"Stable gastric pentadecapeptide BPC 157 in the therapy of the rats with bile duct ligation.","authors":"Sever, Anita Zenko; Sever, Marko; Vidovic, Tinka; Lojo, Nermin; Kolenc, Danijela; Vuletic, Lovorka Batelja; Drmic, Domagoj; Kokot, Antonio; Zoricic, Ivan; Coric, Marijana; Vlainic, Josipa; Poljak, Ljiljana; Seiwerth, Sven; Sikiric, Predrag","year":2019,"journal":"European journal of pharmacology, 847, 130-142","doi":"10.1016/j.ejphar.2019.01.030","pmid":"30690000","tags":["bpc-157"],"studyType":"animal","evidenceStrength":"preliminary","keyFinding":"BPC 157 reversed liver fibrosis and portal hypertension in rats with surgically ligated bile ducts — a well-established model of chronic liver disease. Treatment with BPC 157 (at both 10 μg/kg and 10 ng/kg doses) through multiple routes (drinking water, intraperitoneal injection, or local application) reduced jaundice, ascites, liver nodularity, bile duct dilation, and liver weight abnormalities. At the cellular level, BPC 157 counteracted necrosis, apoptosis, inflammation, hepatic stellate cell activation (the cells that drive fibrosis), and collagen deposition.\n\nLiver function markers normalized (AST, ALT, GGT, ALP, bilirubin improved; albumin increased). Tissue oxidative stress markers (MDA) and nitric oxide levels returned to healthy ranges, with changes in NOS2 and NOS3 expression and reduced inflammatory cytokines (IL-6, TNF-α, IL-1β). Portal hypertension was either prevented entirely or rapidly reversed depending on when BPC 157 treatment began.","whyItMatters":"Liver fibrosis and portal hypertension are major causes of death in chronic liver disease, and current treatments are limited. BPC 157 showed remarkably comprehensive effects in this model — addressing fibrosis, inflammation, cell death, portal pressure, and liver function simultaneously. While this is an animal study, the breadth of effects across multiple outcome measures and the dose-response at very low concentrations make it a notable preclinical finding in the BPC 157 research literature.","specificNumbers":"BPC 157: 10 μg/kg and 10 ng/kg · Multiple routes: oral, IP, local · Sacrifice at 2, 4, 6, 8 weeks · Normalized AST, ALT, GGT, ALP, bilirubin, albumin · Reduced IL-6, TNF-α, IL-1β · Reversed portal hypertension","methodology":"Bile duct ligation (BDL) in rats to induce liver fibrosis and portal hypertension. BPC 157 was administered via three routes: continuously in drinking water, by intraperitoneal injection (starting 30 minutes post-surgery or at week 4), or by local bath application. Rats were sacrificed at 2, 4, 6, and 8 weeks. Outcomes included gross pathology, histology (necrosis, fibrosis, stellate cell activation via α-SMA, collagen via Mallory stain, proliferation via Ki-67), serum liver function tests, tissue oxidative stress and nitric oxide markers, NOS2/NOS3 Western blots, and inflammatory cytokine levels.","limitations":"All results are from rats — no human liver fibrosis data exists for BPC 157. The bile duct ligation model causes obstructive liver disease, which differs from the most common human causes of fibrosis (alcohol, NAFLD, viral hepatitis). The study comes from the Sikiric group in Zagreb, which produces the vast majority of BPC 157 research — independent replication by other groups is limited. The breadth of claimed effects (fibrosis, necrosis, inflammation, portal hypertension, liver function, oxidative stress all reversed) is extraordinary for a single peptide and warrants independent validation."},{"rthcId":"RPEP-04471","title":"Canagliflozin for Japanese patients with chronic heart failure and type II diabetes.","authors":"Sezai, Akira; Sekino, Hisakuni; Unosawa, Satoshi; Taoka, Makoto; Osaka, Shunji; Tanaka, Masashi","year":2019,"journal":"Cardiovascular diabetology, 18(1), 76","doi":"10.1186/s12933-019-0877-2","pmid":"31167663","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04472","title":"Therapeutic Effects of Endogenous Incretin Hormones and Exogenous Incretin-Based Medications in Sepsis.","authors":"Shah, Faraaz Ali; Mahmud, Hussain; Gallego-Martin, Teresa; Jurczak, Michael J; O'Donnell, Christopher P; McVerry, Bryan J","year":2019,"journal":"The Journal of clinical endocrinology and metabolism, 104(11), 5274-5284","doi":"10.1210/jc.2019-00296","pmid":"31216011","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04473","title":"The glucagon-like peptide-1 receptor agonist reduces inflammation and blood-brain barrier breakdown in an astrocyte-dependent manner in experimental stroke.","authors":"Shan, Yilong; Tan, Sha; Lin, Yinyao; Liao, Siyuan; Zhang, Bingjun; Chen, Xiaodong; Wang, Jihui; Deng, Zhezhi; Zeng, Qin; Zhang, Lei; Wang, Yuge; Hu, Xueqiang; Qiu, Wei; Peng, Lisheng; Lu, Zhengqi","year":2019,"journal":"Journal of neuroinflammation, 16(1), 242","doi":"10.1186/s12974-019-1638-6","pmid":"31779652","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04474","title":"A universal anti-cancer vaccine: Chimeric invariant chain potentiates the inhibition of melanoma progression and the improvement of survival.","authors":"Sharbi-Yunger, Adi; Grees, Mareike; Cafri, Gal; Bassan, David; Eichmüller, Stefan B; Tzehoval, Esther; Utikal, Jochen; Umansky, Viktor; Eisenbach, Lea","year":2019,"journal":"International journal of cancer, 144(4), 909-921","doi":"10.1002/ijc.31795","pmid":"30106470","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Researchers created a chimeric vaccine platform by modifying the invariant chain (Ii) — a protein that helps present antigens to the immune system — and replacing its CLIP peptide region with melanoma antigen peptide sequences. When dendritic cells loaded with this modified construct were combined with a separate MHC-I vaccine platform and injected into tumor-bearing mice, the combination activated both CD4+ helper T cells and CD8+ killer T cells, inhibited melanoma tumor growth, and improved survival. The combination approach produced efficient tumor cell killing plus elevated Th1 and Th2 immune responses.","whyItMatters":"Cancer vaccines have struggled because tumors are skilled at evading the immune system. This study demonstrates that engaging both arms of the adaptive immune system — helper T cells (via MHC-II) and killer T cells (via MHC-I) — is more effective than targeting one alone. The 'universal' design means the peptide sequences can be swapped for different tumor antigens, making this platform potentially applicable across multiple cancer types.","specificNumbers":"","methodology":"The researchers engineered chimeric invariant chain mRNA constructs where the CLIP region was replaced with MHC-II-binding melanoma antigen peptides. Dendritic cells were transfected with this mRNA, then injected into C57BL/6 mice bearing melanoma tumors, either alone or combined with an MHC-I DC vaccine platform. They measured tumor growth, mouse survival, CD4+ and CD8+ T cell activation, cytotoxic T cell killing efficiency, and Th1/Th2 cytokine profiles.","limitations":"This is a preclinical mouse study using engineered melanoma models — results may not translate directly to human cancer. The study focused on melanoma antigens only; the 'universal' applicability to other cancers is theoretical. No toxicity, dosing optimization, or long-term follow-up data were reported. The complexity of the dual-platform approach could present manufacturing and regulatory challenges."},{"rthcId":"RPEP-04475","title":"Development and characterization of late-stage diabetes mellitus and -associated vascular complications.","authors":"Sharma, Gunjan; Ashhar, Md Umama; Aeri, Vidhu; Katare, Deepshikha Pande","year":2019,"journal":"Life sciences, 216, 295-304","doi":"10.1016/j.lfs.2018.11.005","pmid":"30408473","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04476","title":"Designing a Tenascin-C-Inspired Short Bioactive Peptide Scaffold to Direct and Control Cellular Behavior.","authors":"Sharma, Pooja; Kaur, Harsimran; Roy, Sangita","year":2019,"journal":"ACS biomaterials science & engineering, 5(12), 6497-6510","doi":"10.1021/acsbiomaterials.9b01115","pmid":"33417802","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04477","title":"Effects of ion concentrations on the hydroxyl radical scavenging rate and reducing power of fish collagen peptides.","authors":"Shen, Quan; Ou, Aining; Liu, Shu; Elango, Jeevithan; Wang, Shujun; Henriques da Silva, Tiago; Wu, Wenhui; Robinson, Jeyashakila; Bao, Bin","year":2019,"journal":"Journal of food biochemistry, 43(4), e12789","doi":"10.1111/jfbc.12789","pmid":"31353598","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04478","title":"Fusion of thymosin alpha 1 with mutant IgG1 CH3 prolongs half-life and enhances antitumor effects in vivo.","authors":"Shen, Xutong; Wang, Liping; Xu, Caoying; Yang, Jiahui; Peng, Renhao; Hu, Xinyi; Wang, Fanwen; Zheng, Heng; Lao, Xingzhen","year":2019,"journal":"International immunopharmacology, 74, 105662","doi":"10.1016/j.intimp.2019.05.047","pmid":"31220695","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04479","title":"The Antitumor Activity of TCR-Mimic Antibody-Drug Conjugates (TCRm-ADCs) Targeting the Intracellular Wilms Tumor 1 (WT1) Oncoprotein.","authors":"Shen, Ying; Li, Yi-Ming; Zhou, Jing-Jing; Zhou, Zhan; Xu, Ying-Chun; Zhao, Wen-Bin; Chen, Shu-Qing","year":2019,"journal":"International journal of molecular sciences, 20(16)","doi":"10.3390/ijms20163912","pmid":"31408937","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04480","title":"Role of neurotransmitters 5-hydroxytryptamine and substance P in anorexia induction following oral exposure to the trichothecene T-2 toxin.","authors":"Sheng, Kun; Lu, Xi; Yue, Jianming; Gu, Wei; Gu, Chao; Zhang, Haibin; Wu, Wenda","year":2019,"journal":"Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 123, 1-8","doi":"10.1016/j.fct.2018.10.041","pmid":"30336258","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04481","title":"Plant defensins: types, mechanism of action and prospects of genetic engineering for enhanced disease resistance in plants.","authors":"Sher Khan, Raham; Iqbal, Aneela; Malak, Radia; Shehryar, Kashmala; Attia, Syeda; Ahmed, Talaat; Ali Khan, Mubarak; Arif, Muhammad; Mii, Masahiro","year":2019,"journal":"3 Biotech, 9(5), 192","doi":"10.1007/s13205-019-1725-5","pmid":"31065492","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04482","title":"SpyLigase-Catalyzed Modification of Antibodies.","authors":"Siegmund, Vanessa; Piater, Birgit; Fischer, Frank; Kolmar, Harald","year":2019,"journal":"Methods in molecular biology (Clifton, N.J.), 2012, 171-192","doi":"10.1007/978-1-4939-9546-2_10","pmid":"31161509","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04483","title":"A New Topical Eye Drop Containing LyeTxI-b, A Synthetic Peptide Designed from A Lycosa erithrognata Venom Toxin, Was Effective to Treat Resistant Bacterial Keratitis.","authors":"Silva, Carolina Nunes da; Silva, Flavia Rodrigues da; Dourado, Lays Fernanda Nunes; Reis, Pablo Victor Mendes Dos; Silva, Rummenigge Oliveira; Costa, Bruna Lopes da; Nunes, Paula Santos; Amaral, Flávio Almeida; Santos, Vera Lúcia Dos; de Lima, Maria Elena; Silva Cunha Júnior, Armando da","year":2019,"journal":"Toxins, 11(4)","doi":"10.3390/toxins11040203","pmid":"30987317","tags":[],"studyType":"animal study","evidenceStrength":"low","keyFinding":"Eye drops containing LyeTxI-b — a synthetic antimicrobial peptide designed from a Brazilian wolf spider (Lycosa erithrognatha) venom toxin — effectively treated resistant bacterial keratitis in rabbits with no signs of ocular toxicity. The peptide killed planktonic Staphylococcus aureus bacteria at a very low concentration (MIC 3.6 μmol/L), reduced biofilm viability by 90%, and when applied as drops four times daily for one week, eliminated bacteria and reduced inflammatory cell activity to levels comparable to healthy untreated eyes. Toxicity testing on chorioallantoic membranes and the standard Draize eye irritation test showed no adverse effects.","whyItMatters":"Bacterial keratitis (corneal infection) can cause rapid, severe vision loss and is a leading cause of corneal blindness worldwide. Antibiotic-resistant strains of Staphylococcus aureus are increasingly common, and bacteria protected within biofilms on the corneal surface are notoriously difficult to treat. Spider venom-derived peptides offer a fundamentally different antimicrobial mechanism than conventional antibiotics — they typically disrupt bacterial membranes, making resistance development much harder. The added anti-inflammatory activity of LyeTxI-b addresses both the infection and the damaging immune response.","specificNumbers":"MIC 3.6 μmol/L · 90% biofilm viability reduction · 4 drops/day for 7 days · 4 × 10⁵ S. aureus cells for infection induction · No ocular toxicity","methodology":"Researchers induced bacterial keratitis in New Zealand white rabbits by intrastromal injection of S. aureus (4 × 10⁵ cells). The peptide eye drop formulation (LyeTxI-b 28.9 μmol/L in 0.5% CMC and 0.9% NaCl) was instilled four times daily for one week. Outcomes included slit-lamp biomicroscopy, corneal histopathology, and quantification of inflammatory cell infiltration through myeloperoxidase (MPO) and N-acetylglucosaminidase (NAG) assays. Ocular safety was assessed via chorioallantoic membrane and Draize tests. In vitro MIC and biofilm viability assays were also performed.","limitations":"This is a rabbit model — ocular pharmacokinetics and immune responses differ between rabbits and humans. The study tested only S. aureus, so efficacy against other keratitis pathogens (Pseudomonas, fungi) is unknown. Sample sizes for the animal experiments are not specified in the abstract. The one-week treatment duration doesn't address whether longer courses would be needed for more severe infections. Manufacturing, stability, and cost considerations for a clinical formulation are not discussed."},{"rthcId":"RPEP-04484","title":"Effects of obesity induced by high-calorie diet and its treatment with exenatide on muscarinic acetylcholine receptors in rat hippocampus.","authors":"Silva, Marcelo Florencio Passos; Alves, Patricia Lucio; Alponti, Rafaela Fadoni; Silveira, Paulo Flavio; Abdalla, Fernando Maurício Francis","year":2019,"journal":"Biochemical pharmacology, 169, 113630","doi":"10.1016/j.bcp.2019.113630","pmid":"31491414","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04485","title":"Long-Term Safety and Efficacy of Bremelanotide for Hypoactive Sexual Desire Disorder.","authors":"Simon, James A; Kingsberg, Sheryl A; Portman, David; Williams, Laura A; Krop, Julie; Jordan, Robert; Lucas, Johna; Clayton, Anita H","year":2019,"journal":"Obstetrics and gynecology, 134(5), 909-917","doi":"10.1097/AOG.0000000000003514","pmid":"31599847","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04486","title":"SAVOR-TIMI to DECLARE-TIMI: A Review on Cardiovascular Outcome Trials of Incretin-modulators and Gliflozins.","authors":"Singh, Awadhesh K; Singh, Ritu","year":2019,"journal":"Indian journal of endocrinology and metabolism, 23(2), 175-183","doi":"10.4103/ijem.IJEM_12_19","pmid":"31161099","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04487","title":"Recent structural advances in constrained helical peptides.","authors":"Skowron, Kornelia J; Speltz, Thomas E; Moore, Terry W","year":2019,"journal":"Medicinal research reviews, 39(2), 749-770","doi":"10.1002/med.21540","pmid":"30307621","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04488","title":"Inhibition of natriuretic peptide receptor 1 reduces itch in mice.","authors":"Solinski, Hans Jürgen; Dranchak, Patricia; Oliphant, Erin; Gu, Xinglong; Earnest, Thomas W; Braisted, John; Inglese, James; Hoon, Mark A","year":2019,"journal":"Science translational medicine, 11(500)","doi":"10.1126/scitranslmed.aav5464","pmid":"31292265","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04489","title":"The role of olefin geometry in the activity of hydrocarbon stapled peptides targeting eukaryotic translation initiation factor 4E (eIF4E).","authors":"Song, James M; Gallagher, Erin E; Menon, Arya; Mishra, Lauren D; Garner, Amanda L","year":2019,"journal":"Organic & biomolecular chemistry, 17(26), 6414-6419","doi":"10.1039/c9ob01041f","pmid":"31215581","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04490","title":"Cyclic Cell-Penetrating Peptides with Single Hydrophobic Groups.","authors":"Song, Jian; Qian, Ziqing; Sahni, Ashweta; Chen, Kuangyu; Pei, Dehua","year":2019,"journal":"Chembiochem : a European journal of chemical biology, 20(16), 2085-2088","doi":"10.1002/cbic.201900370","pmid":"31298779","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04491","title":"Identification and Structure-Activity Relationship of Intestinal Epithelial Barrier Function Protective Collagen Peptides from Alaska Pollock Skin.","authors":"Song, Wenkui; Chen, Qianru; Wang, Ying; Han, Yan; Zhang, Hongwei; Li, Bo","year":2019,"journal":"Marine drugs, 17(8)","doi":"10.3390/md17080450","pmid":"31370332","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04492","title":"Permeation of beta-defensin-3 encapsulated with polyethylene glycol in lung surfactant models at air-water interface.","authors":"Souza, F R; Souza, L M P; Pimentel, A S","year":2019,"journal":"Colloids and surfaces. B, Biointerfaces, 182, 110357","doi":"10.1016/j.colsurfb.2019.110357","pmid":"31351272","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04493","title":"Integrated evolutionary analysis reveals antimicrobial peptides with limited resistance.","authors":"Spohn, Réka; Daruka, Lejla; Lázár, Viktória; Martins, Ana; Vidovics, Fanni; Grézal, Gábor; Méhi, Orsolya; Kintses, Bálint; Számel, Mónika; Jangir, Pramod K; Csörgő, Bálint; Györkei, Ádám; Bódi, Zoltán; Faragó, Anikó; Bodai, László; Földesi, Imre; Kata, Diána; Maróti, Gergely; Pap, Bernadett; Wirth, Roland; Papp, Balázs; Pál, Csaba","year":2019,"journal":"Nature communications, 10(1), 4538","doi":"10.1038/s41467-019-12364-6","pmid":"31586049","tags":["antimicrobial-peptides"],"studyType":"basic-research","evidenceStrength":"strong","keyFinding":"In a systematic comparison of resistance evolution against 14 antimicrobial peptides and 12 conventional antibiotics in E. coli, certain AMPs — specifically tachyplesin II and cecropin P1 — showed remarkably limited resistance development. Three lines of evidence supported this: (1) point mutations and gene amplification provided very low resistance levels against these AMPs, (2) bacteria already resistant to conventional antibiotics showed no cross-resistance to these AMPs, and (3) even when genomic fragments from a wide range of soil bacteria were introduced on plasmids, no detectable resistance to these AMPs emerged.\n\nThe researchers identified simple physicochemical features of AMPs that predict whether bacteria can evolve resistance — providing a roadmap for designing resistance-proof peptide antibiotics.","whyItMatters":"The biggest argument against developing antimicrobial peptides as drugs has been: won't bacteria just evolve resistance to them too? This Nature Communications study provides the strongest evidence yet that certain AMPs may be truly resistance-proof — bacteria can't easily develop point mutations, gene amplifications, or acquire resistance genes from other bacteria to overcome them. This transforms AMPs from 'promising but risky' to 'strategically essential' in the fight against antibiotic resistance.","specificNumbers":"14 AMPs tested · 12 antibiotics compared · Tachyplesin II and cecropin P1 showed limited resistance · No cross-resistance from antibiotic-resistant strains · Soil metagenomics found no resistance genes · Physicochemical features predict resistance potential","methodology":"Systematic experimental evolution study in E. coli. Bacteria were exposed to increasing concentrations of 14 chemically diverse AMPs and 12 antibiotics over multiple generations to evolve resistance. Resistance mechanisms were characterized through genomic analysis (point mutations, gene amplifications). Cross-resistance between antibiotics and AMPs was tested. A functional metagenomics approach introduced genomic fragments from diverse soil bacteria into E. coli to search for naturally occurring resistance genes.","limitations":"All experiments were in E. coli — resistance patterns may differ in other bacterial species, especially Gram-positive bacteria or clinical pathogens. Laboratory evolution under controlled conditions may not fully replicate the complexity of resistance development in real-world infections. The soil metagenomics approach, while powerful, cannot test every possible environmental resistance gene. The physicochemical features identified need validation across more peptide structures."},{"rthcId":"RPEP-04494","title":"Systemically administered peptain-1 inhibits retinal ganglion cell death in animal models: implications for neuroprotection in glaucoma.","authors":"Stankowska, Dorota L; Nam, Mi-Hyun; Nahomi, Rooban B; Chaphalkar, Renuka M; Nandi, Sandip K; Fudala, Rafal; Krishnamoorthy, Raghu R; Nagaraj, Ram H","year":2019,"journal":"Cell death discovery, 5, 112","doi":"10.1038/s41420-019-0194-2","pmid":"31285855","tags":[],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"Peptain-1, a peptide with chaperone and anti-apoptotic properties, protected retinal ganglion cells (RGCs) from death in two rodent models of glaucoma. When injected into the abdomen, the peptide crossed the blood-retinal barrier and reached the retina.\n\nKey results across models:\n- In ischemia/reperfusion injury mice: peptain-1 inhibited RGC loss and improved impaired axonal transport\n- In rats with 5 weeks of elevated eye pressure: peptain-1 significantly reduced both RGC death and axon loss, and partially restored mitochondrial COX 6b2 levels\n- In cell culture and retinal explants: peptain-1 significantly reduced hypoxia-induced RGC death compared to scrambled peptide control","whyItMatters":"Glaucoma is the leading cause of irreversible blindness worldwide, and the only current treatment is lowering eye pressure — which doesn't work for everyone and doesn't directly protect the dying nerve cells. Peptain-1 represents a fundamentally different approach: directly protecting the retinal ganglion cells that glaucoma destroys. The fact that it works when injected systemically (not into the eye) and crosses the blood-retinal barrier makes it far more practical than eye-injection-only therapies.","specificNumbers":"2 rodent models · 5 weeks elevated intraocular pressure · blood-retinal barrier crossing confirmed · RGC somas and axons protected · mitochondrial COX 6b2 partially restored · scrambled peptide control used","methodology":"Multi-model preclinical study. Researchers tested peptain-1 in cultured rat retinal ganglion cells, rat retinal explants, a mouse ischemia/reperfusion injury model, and a rat model of chronic elevated intraocular pressure (5 weeks). Peptain-1 was administered via intraperitoneal injection. Retinal penetration was confirmed using a fluorescent-labeled version (Cy7 conjugate). RGC survival, axonal transport, and mitochondrial protein levels were measured.","limitations":"Animal models only — rodent glaucoma models don't perfectly replicate the slow, chronic disease seen in humans over decades. Dosing details and duration of protective effect after stopping treatment were not described. Long-term safety of systemic peptain-1 was not assessed. The study doesn't address whether the peptide would work in human eyes, which have different blood-retinal barrier properties."},{"rthcId":"RPEP-04495","title":"HOPS-dependent endosomal fusion required for efficient cytosolic delivery of therapeutic peptides and small proteins.","authors":"Steinauer, Angela; LaRochelle, Jonathan R; Knox, Susan L; Wissner, Rebecca F; Berry, Samuel; Schepartz, Alanna","year":2019,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 116(2), 512-521","doi":"10.1073/pnas.1812044116","pmid":"30610181","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04496","title":"Substance P and neurokinin 1 receptor are new targets for the treatment of chronic pruritus.","authors":"Ständer, S; Yosipovitch, G","year":2019,"journal":"The British journal of dermatology, 181(5), 932-938","doi":"10.1111/bjd.18025","pmid":"31016733","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04497","title":"Nanofiber Dressings Topically Delivering Molecularly Engineered Human Cathelicidin Peptides for the Treatment of Biofilms in Chronic Wounds.","authors":"Su, Yajuan; Wang, Hongjun; Mishra, Biswajit; Lakshmaiah Narayana, Jayaram; Jiang, Jiang; Reilly, Debra A; Hollins, Ronald R; Carlson, Mark A; Wang, Guangshun; Xie, Jingwei","year":2019,"journal":"Molecular pharmaceutics, 16(5), 2011-2020","doi":"10.1021/acs.molpharmaceut.8b01345","pmid":"30916573","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04498","title":"Therapy of the rat hemorrhagic cystitis induced by cyclophosphamide. Stable gastric pentadecapeptide BPC 157, L-arginine, L-NAME.","authors":"Sucic, Mario; Luetic, Kresimir; Jandric, Ivan; Drmic, Domagoj; Sever, Anita Zenko; Vuletic, Lovorka Batelja; Halle, Zeljka Belosic; Strinic, Dean; Kokot, Antonio; Seiwerth, Ranka Serventi; Zoricic, Ivan; Blagaic, Alenka Boban; Seiwerth, Sven; Sikiric, Predrag","year":2019,"journal":"European journal of pharmacology, 861, 172593","doi":"10.1016/j.ejphar.2019.172593","pmid":"31401154","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04499","title":"Recombinant Oncolytic Vaccinia Viruses Expressing Human β-Defensin 2 Enhance Anti-tumor Immunity.","authors":"Sun, Ting; Luo, Yanxi; Wang, Minglong; Xie, Tian; Yan, Hui","year":2019,"journal":"Molecular therapy oncolytics, 13, 49-57","doi":"10.1016/j.omto.2019.03.010","pmid":"31011627","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A recombinant oncolytic vaccinia virus engineered to express human β-defensin 2 (HBD2) — an antimicrobial peptide of the innate immune system — significantly inhibited tumor growth and metastasis in a mouse melanoma model. The HBD2-expressing virus recruited plasmacytoid dendritic cells to the tumor site, which then activated both CD4+ and CD8+ tumor-infiltrating T cells. This triggered both innate and adaptive immune responses against the cancer.","whyItMatters":"This study demonstrates an innovative approach: using an antimicrobial peptide (HBD2) not to fight infection, but to fight cancer. By engineering a cancer-killing virus to also produce this immune-stimulating peptide, researchers created a dual-action therapy that both destroys tumor cells directly and recruits the immune system. It represents a creative cross-application of peptide biology from infectious disease to oncology.","specificNumbers":"VV-HBD2-lacZ construct · HBD2 attracted dendritic cells in vitro and in vivo · increased CD4+ and CD8+ T cells in tumors · significantly inhibited tumor growth and metastasis · mouse melanoma model","methodology":"Researchers constructed a recombinant vaccinia virus (VV-HBD2-lacZ) expressing human β-defensin 2. They tested HBD2's ability to attract dendritic cells in vitro and in vivo, then evaluated anti-tumor effects in a mouse melanoma model. Tumor growth, metastasis, and immune cell infiltration (CD4+ and CD8+ T cells) were assessed.","limitations":"This is a preclinical mouse study using a melanoma model, which may not translate directly to human cancers. The long-term safety of using an oncolytic virus expressing a human antimicrobial peptide was not assessed. The study did not compare the HBD2-expressing virus to other immunostimulatory gene insertions. Potential off-target immune activation by HBD2 was not fully evaluated."},{"rthcId":"RPEP-04500","title":"Very Short and Stable Lactoferricin-Derived Antimicrobial Peptides: Design Principles and Potential Uses.","authors":"Svendsen, John S Mjøen; Grant, Thomas M; Rennison, David; Brimble, Margaret A; Svenson, Johan","year":2019,"journal":"Accounts of chemical research, 52(3), 749-759","doi":"10.1021/acs.accounts.8b00624","pmid":"30829472","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04501","title":"Enkephalinase inhibitors, potential therapeutics for the future treatment of diarrhea predominant functional gastrointestinal disorders.","authors":"Szymaszkiewicz, Agata; Storr, Martin; Fichna, Jakub; Zielinska, Marta","year":2019,"journal":"Neurogastroenterology and motility, 31(4), e13526","doi":"10.1111/nmo.13526","pmid":"30549162","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04502","title":"Substance P induces fibrotic changes through activation of the RhoA/ROCK pathway in an in vitro human corneal fibrosis model.","authors":"Słoniecka, Marta; Danielson, Patrik","year":2019,"journal":"Journal of molecular medicine (Berlin, Germany), 97(10), 1477-1489","doi":"10.1007/s00109-019-01827-4","pmid":"31399750","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04503","title":"Butyric Acid and Leucine Induce α-Defensin Secretion from Small Intestinal Paneth Cells.","authors":"Takakuwa, Akiko; Nakamura, Kiminori; Kikuchi, Mani; Sugimoto, Rina; Ohira, Shuya; Yokoi, Yuki; Ayabe, Tokiyoshi","year":2019,"journal":"Nutrients, 11(11)","doi":"10.3390/nu11112817","pmid":"31752111","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04504","title":"Molecular cloning and analysis of Suncus murinus group IIA secretary phospholipase A2 expression.","authors":"Takemi, Shota; Nishio, Ryo; Taguchi, Hayato; Ojima, Shiomi; Matsumoto, Mio; Sakai, Takafumi; Sakata, Ichiro","year":2019,"journal":"Developmental and comparative immunology, 100, 103427","doi":"10.1016/j.dci.2019.103427","pmid":"31278953","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04505","title":"New Engineered-Botulinum Toxins Inhibit the Release of Pain-Related Mediators.","authors":"Tang, Minhong; Meng, Jianghui; Wang, Jiafu","year":2019,"journal":"International journal of molecular sciences, 21(1)","doi":"10.3390/ijms21010262","pmid":"31906003","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04506","title":"Anti-parasitic effect on Toxoplasma gondii induced by a spider peptide lycosin-I.","authors":"Tang, Yaqin; Hou, Shengjie; Li, Xianyao; Wu, Mengqi; Ma, Binbin; Wang, Zheng; Jiang, Jinying; Deng, Meichun; Duan, Zhigui; Tang, Xing; Liu, Yuan; Wang, Wenhua; Han, Xiaoqing; Jiang, Liping","year":2019,"journal":"Experimental parasitology, 198, 17-25","doi":"10.1016/j.exppara.2019.01.009","pmid":"30682337","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04507","title":"New generation CPPs show distinct selectivity for cancer and noncancer cells.","authors":"Tansi, Felista L; Filatova, Margarita P; Koroev, Dmitri O; Volpina, Olga M; Lange, Steffi; Schumann, Christina; Teichgräber, Ulf K; Reissmann, Siegmund; Hilger, Ingrid","year":2019,"journal":"Journal of cellular biochemistry, 120(4), 6528-6541","doi":"10.1002/jcb.27943","pmid":"30362167","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04508","title":"Exenatide ameliorates inflammatory response in human rheumatoid arthritis fibroblast-like synoviocytes.","authors":"Tao, Yunxia; Ge, Gaoran; Wang, Qing; Wang, Wei; Zhang, Wenhao; Bai, Jiaxiang; Lin, Jiayi; Shen, Jining; Guo, Xiaobin; Xu, Yaozeng; Geng, Dechun","year":2019,"journal":"IUBMB life, 71(7), 969-977","doi":"10.1002/iub.2031","pmid":"30897288","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Exenatide, acting through the GLP-1 receptor on human fibroblast-like synoviocytes (FLS), demonstrated multiple anti-inflammatory and protective effects in RA joint cells stimulated with TNF-α. Specifically, exenatide:\n\n- Increased mitochondrial membrane potential, reversing TNF-α-induced mitochondrial dysfunction\n- Reduced reactive oxygen species (ROS) production and NADPH oxidase 4 expression\n- Decreased expression of tissue-degrading enzymes MMP-3 and MMP-13\n- Lowered release of proinflammatory cytokines IL-1β, IL-6, MCP-1, and HMGB1\n- Inhibited the p38/IκBα/NF-κB signaling pathway, a key inflammatory cascade","whyItMatters":"Rheumatoid arthritis affects millions worldwide and current treatments have significant side effects or lose effectiveness over time. Finding new anti-inflammatory uses for existing, well-characterized drugs like exenatide could accelerate the path to new RA therapies. This study also reveals that GLP-1 receptors exist on joint cells — a finding that opens a new avenue for understanding how metabolic and inflammatory pathways intersect.","specificNumbers":"","methodology":"The researchers used primary human fibroblast-like synoviocytes (FLS) from rheumatoid arthritis patients grown in cell culture. They stimulated these cells with TNF-α to mimic the inflammatory environment of an RA joint, then treated them with exenatide. They measured changes in mitochondrial function, oxidative stress markers, inflammatory cytokines, matrix metalloproteinases, and signaling pathway activation.","limitations":"This was an in vitro study using cells in a dish, not a clinical trial. The inflammatory conditions were artificially induced with TNF-α, which may not fully replicate the complex inflammatory environment of an RA joint. Specific concentrations of exenatide used and whether they are achievable in joint tissue in vivo were not discussed in the abstract. No animal model or human clinical data was presented."},{"rthcId":"RPEP-04509","title":"CGRP, Amylin, Immunology, and Headache Medicine.","authors":"Taylor, Frederick R","year":2019,"journal":"Headache, 59(1), 131-150","doi":"10.1111/head.13432","pmid":"30390312","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04510","title":"The Effects of a Novel Series of KTTKS Analogues on Cytotoxicity and Proteolytic Activity.","authors":"Tałałaj, Urszula; Uścinowicz, Paulina; Bruzgo, Irena; Surażyński, Arkadiusz; Zaręba, Ilona; Markowska, Agnieszka","year":2019,"journal":"Molecules (Basel, Switzerland), 24(20)","doi":"10.3390/molecules24203698","pmid":"31618846","tags":["cosmetic-peptides"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"A series of novel KTTKS analogues — modified versions of the collagen-derived pentapeptide used in Matrixyl® skincare — were synthesized and tested for protease inhibition, cytotoxicity, and collagen stimulation in fibroblast cultures.\n\nThe palmitoyl-modified peptides were the most potent plasmin inhibitors, regardless of whether they were in acid or amide form. Swapping lysine for arginine in the sequences had no measurable biological effect. None of the synthesized analogues were cytotoxic to fibroblasts, and three of them promoted fibroblast cell growth. However, those three growth-promoting peptides did not show a clear concentration-dependent relationship in collagen or DNA biosynthesis assays.","whyItMatters":"KTTKS (marketed as Matrixyl®) is one of the most widely used peptides in anti-aging skincare. This study explored whether chemical modifications to the KTTKS backbone could improve its stability or biological activity. The finding that palmitoyl versions were strong plasmin inhibitors is notable because plasmin breaks down extracellular matrix proteins — blocking it could theoretically help preserve collagen in skin. The lack of cytotoxicity across all analogues is reassuring for potential topical applications.","specificNumbers":"","methodology":"Researchers designed and synthesized a series of pentapeptides based on the KTTKS sequence, modifying them with acetyl, lipoyl, or palmitoyl groups. They tested each analogue's ability to inhibit six proteases (urokinase, thrombin, trypsin, plasmin, t-PA, and kallikrein). Cytotoxicity was assessed on cultured fibroblasts, and selected peptides were further tested for their effects on collagen and DNA biosynthesis.","limitations":"This was an in vitro study using cultured fibroblasts, so results may not translate to intact human skin. The peptides that promoted cell growth did not show dose-response relationships in collagen/DNA synthesis assays, making it hard to determine optimal concentrations. No skin penetration or in vivo testing was performed."},{"rthcId":"RPEP-04511","title":"A scorpion venom peptide derivative BmKn‒22 with potent antibiofilm activity against Pseudomonas aeruginosa.","authors":"Teerapo, Kittitat; Roytrakul, Sittiruk; Sistayanarain, Anchalee; Kunthalert, Duangkamol","year":2019,"journal":"PloS one, 14(6), e0218479","doi":"10.1371/journal.pone.0218479","pmid":"31199859","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04512","title":"Mast Cells, Neuroinflammation and Pain in Fibromyalgia Syndrome.","authors":"Theoharides, Theoharis C; Tsilioni, Irene; Bawazeer, Mona","year":2019,"journal":"Frontiers in cellular neuroscience, 13, 353","doi":"10.3389/fncel.2019.00353","pmid":"31427928","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Previous work by this group found that fibromyalgia patients had significantly increased serum levels of substance P, hemokinin-1 (HK-1), IL-6, and TNF compared to sedentary controls.\n\nBased on these findings, the authors propose a mechanistic hypothesis: mast cells in the thalamus release neuro-sensitizing molecules — including histamine, IL-1β, IL-6, TNF, CGRP, HK-1, and substance P — that activate thalamic pain-processing neurons either directly or via microglial stimulation. This creates a neuroinflammatory cycle that could explain the chronic, widespread pain of fibromyalgia. They suggest that inhibiting mast cell activation could be a novel therapeutic approach.","whyItMatters":"Fibromyalgia affects an estimated 2-4% of the population globally, predominantly women, yet there is no clearly defined pathogenesis and treatments are often inadequate. This hypothesis directly connects measurable neuropeptide abnormalities (substance P, CGRP, hemokinin-1) to a specific cellular mechanism (thalamic mast cell activation), potentially opening new therapeutic avenues. Mast cell stabilizers already exist and are used for other conditions, making this hypothesis testable with existing drugs.","specificNumbers":"","methodology":"This paper reviews the authors' previous clinical findings (elevated neuropeptides and cytokines in fibromyalgia patients vs. controls) and synthesizes them with existing literature on mast cell biology, neuroinflammation, and pain signaling to propose a mechanistic model. It is a hypothesis-driven review rather than a primary experimental study.","limitations":"This is primarily a hypothesis paper that proposes a mechanism based on the authors' previous findings and existing literature. The thalamic mast cell hypothesis has not been directly tested with experiments demonstrating causation. The elevated neuropeptide levels in serum may not reflect brain concentrations. The role of mast cells in the thalamus specifically in fibromyalgia has not been confirmed with human brain tissue studies. The hypothesis, while plausible, remains to be validated."},{"rthcId":"RPEP-04513","title":"Disrupted hippocampal growth hormone secretagogue receptor 1α interaction with dopamine receptor D1 plays a role in Alzheimer's disease.","authors":"Tian, Jing; Guo, Lan; Sui, Shaomei; Driskill, Christopher; Phensy, Aarron; Wang, Qi; Gauba, Esha; Zigman, Jeffrey M; Swerdlow, Russell H; Kroener, Sven; Du, Heng","year":2019,"journal":"Science translational medicine, 11(505)","doi":"10.1126/scitranslmed.aav6278","pmid":"31413143","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04514","title":"MK0677, a Ghrelin Mimetic, Improves Neurogenesis but Fails to Prevent Hippocampal Lesions in a Mouse Model of Alzheimer's Disease Pathology.","authors":"Tian, Jing; Wang, Tienju; Wang, Qi; Guo, Lan; Du, Heng","year":2019,"journal":"Journal of Alzheimer's disease : JAD, 72(2), 467-478","doi":"10.3233/JAD-190779","pmid":"31594237","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"MK0677, a potent ghrelin mimetic that activates the growth hormone secretagogue receptor (GHSR1α), improved hippocampal neurogenesis in 5xFAD Alzheimer's model mice when given at the asymptomatic stage. However, it failed to prevent amyloid-β deposition, synaptic loss, microglial activation, or cognitive impairment. At a dose of 3 mg/kg, MK0677 significantly increased mortality in these mice. Despite promoting new neuron formation, ghrelin receptor activation alone was insufficient to protect against Alzheimer's pathology.","whyItMatters":"This is an important negative result. Ghrelin and its receptor had been proposed as potential therapeutic targets for Alzheimer's disease based on their role in promoting synaptic function and neurogenesis. This study, combined with a previously failed large-scale clinical trial, demonstrates that MK0677 alone is not effective for AD prevention or treatment. This redirects the field away from a promising but ultimately unsuccessful approach and saves resources that might have been spent on further development of this strategy.","specificNumbers":"3 mg/kg dose increased mortality · Improved neurogenesis · No prevention of Aβ deposition · No synaptic protection · No cognitive benefit · Failed large-scale clinical trial cited","methodology":"Preclinical study using 5xFAD transgenic mice (a model of AD-like amyloidosis) treated with MK0677 beginning at the asymptomatic stage. Researchers assessed hippocampal neurogenesis, amyloid-β deposition, synaptic integrity, microglial activation, cognitive function (behavioral testing), and survival across treatment groups.","limitations":"The 5xFAD model produces aggressive amyloid pathology that may be more severe than typical human AD progression, potentially overwhelming any protective effects. The study tested only one ghrelin mimetic (MK0677) and did not test actual ghrelin peptide or combination therapies. The mechanism behind increased mortality at 3 mg/kg was not fully explored."},{"rthcId":"RPEP-04515","title":"An Albumin Sandwich Enhances in Vivo Circulation and Stability of Metabolically Labile Peptides.","authors":"Tian, Rui; Zhu, Shoujun; Zeng, Qiao; Lang, Lixin; Ma, Ying; Kiesewetter, Dale O; Liu, Yi; Fu, Xiao; Lau, Joseph; Zhu, Guizhi; Jacobson, Orit; Wang, Zhantong; Dai, Yunlu; Yu, Guocan; Brooks, Bernard R; Liu, Gang; Niu, Gang; Chen, Xiaoyuan","year":2019,"journal":"Bioconjugate chemistry, 30(6), 1711-1723","doi":"10.1021/acs.bioconjchem.9b00258","pmid":"31082207","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04516","title":"A method for confirming CJC-1295 abuse in equine plasma samples by LC-MS/MS.","authors":"Timms, Mark; Ganio, Katherine; Steel, Rohan","year":2019,"journal":"Drug testing and analysis, 11(8), 1248-1257","doi":"10.1002/dta.2599","pmid":"30938069","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04517","title":"An immuno polymerase chain reaction screen for the detection of CJC-1295 and other growth-hormone-releasing hormone analogs in equine plasma.","authors":"Timms, Mark; Ganio, Katherine; Forbes, Grace; Bailey, Simon; Steel, Rohan","year":2019,"journal":"Drug testing and analysis, 11(6), 804-812","doi":"10.1002/dta.2554","pmid":"30489688","tags":["CJC-1295","doping-detection"],"studyType":"experimental","evidenceStrength":"moderate","keyFinding":"Researchers developed an immuno-polymerase chain reaction (I-PCR) assay capable of detecting CJC-1295 — a growth hormone-releasing peptide — in horse blood at concentrations as low as 0.8 pg/mL. CJC-1295 is uniquely difficult to detect because it contains a reactive chemical group that covalently bonds to blood proteins, turning the peptide into a macromolecule that standard mass spectrometry screening cannot identify.\n\nUsing monoclonal antibodies specific to CJC-1295, the assay was validated in thoroughbred racehorses after administration of the drug. A screening threshold of 50 pg/mL was established to distinguish CJC-1295 from naturally occurring equine GHRH. The method confirmed detection of the peptide-protein conjugate in real-world samples.","whyItMatters":"CJC-1295 has been essentially invisible to standard drug testing because it binds to blood proteins and hides from conventional detection methods. This new assay closes that gap for equine sports, and the same approach could potentially be adapted for human anti-doping testing. It highlights how peptide drugs can be engineered to evade detection and how testing must evolve to keep up.","specificNumbers":"detection limit 0.8 pg/mL · screening threshold 50 pg/mL · 30 amino acid peptide · validated in thoroughbred racehorses","methodology":"Developed a pair of monoclonal antibodies targeting the CJC-1295 peptide, then built an immuno-PCR assay that amplifies the detection signal to identify CJC-1295-protein conjugates at extremely low concentrations. Validated by administering CJC-1295 to thoroughbred racehorses and testing blood samples.","limitations":"The study focused on equine plasma, so direct applicability to human anti-doping testing would require additional validation. The 50 pg/mL threshold was set to avoid false positives from endogenous horse GHRH, but the threshold for human testing may differ. Sample size of horses tested was not specified in the abstract."},{"rthcId":"RPEP-04518","title":"Effects of a High-Protein/Moderate-Carbohydrate Diet on Appetite, Gut Peptides, and Endocannabinoids-A Preview Study.","authors":"Tischmann, Lea; Drummen, Mathijs; Gatta-Cherifi, Blandine; Raben, Anne; Fogelholm, Mikael; Hartmann, Bolette; Holst, Jens J; Matias, Isabelle; Cota, Daniela; Mensink, Ronald P; Joris, Peter J; Westerterp-Plantenga, Margriet S; Adam, Tanja C","year":2019,"journal":"Nutrients, 11(10)","doi":"10.3390/nu11102269","pmid":"31546629","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The high-protein/moderate-carbohydrate (HP/MCHO) diet reduced hunger perception by 56.6% compared to the moderate-protein/high-carbohydrate (MP/HCHO) diet (p<0.05), measured approximately 34 months after initial weight loss.\n\nThe decreased hunger on the HP/MCHO diet was significantly associated with increased 2-AG (endocannabinoid) concentrations (p<0.05) and increased PYY (satiety peptide) concentrations (p<0.01). However, ad libitum food intake, insulin resistance (HOMA-IR), and incremental areas under the curve for GLP-1 and PYY were not significantly different between the two diet conditions.","whyItMatters":"Weight regain after dieting is extremely common, and persistent hunger is a key driver. This study shows that maintaining a higher protein intake can reduce hunger even years after weight loss, and identifies specific biological mechanisms — involving the gut peptide PYY and the endocannabinoid system — that mediate this effect. Understanding these pathways could help design better long-term weight management strategies.","specificNumbers":"","methodology":"Crossover study in a 48-hour respiration chamber with 38 participants (22 female, 16 male; mean age 64.5 years; BMI 28.9 kg/m²) approximately 34 months after weight loss. Participants were fed in energy balance with either a HP/MCHO diet (25:45:30 protein:carb:fat) or MP/HCHO diet (15:55:30). Researchers measured endocannabinoids and related compounds, postprandial GLP-1 and PYY levels, subjective hunger and satiety, and ad libitum food intake.","limitations":"The sample size of 38 participants is relatively small. The study measured hunger perception but found no difference in actual ad libitum food intake, raising questions about the practical significance of the hunger reduction. The respiration chamber setting may not reflect real-world eating behavior. The study was conducted in post-obese older adults, so results may not generalize to younger populations or those currently losing weight. The 48-hour measurement window may not capture longer-term effects."},{"rthcId":"RPEP-04519","title":"Ghrelin and the heart.","authors":"Tokudome, Takeshi; Otani, Kentaro; Miyazato, Mikiya; Kangawa, Kenji","year":2019,"journal":"Peptides, 111, 42-46","doi":"10.1016/j.peptides.2018.05.006","pmid":"29791869","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04520","title":"Physiological significance of ghrelin in the cardiovascular system.","authors":"Tokudome, Takeshi; Kangawa, Kenji","year":2019,"journal":"Proceedings of the Japan Academy. Series B, Physical and biological sciences, 95(8), 459-467","doi":"10.2183/pjab.95.032","pmid":"31611501","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04521","title":"RTD-1 therapeutically normalizes synovial gene signatures in rat autoimmune arthritis and suppresses proinflammatory mediators in RA synovial fibroblasts.","authors":"Tongaonkar, Prasad; Punj, Vasu; Subramanian, Akshay; Tran, Dat Q; Trinh, Katie K; Schaal, Justin B; Laragione, Teresina; Ouellette, André J; Gulko, Percio S; Selsted, Michael E","year":2019,"journal":"Physiological genomics, 51(12), 657-667","doi":"10.1152/physiolgenomics.00066.2019","pmid":"31762409","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04522","title":"How much do calcitonin gene-related peptide monoclonal antibodies improve the quality of life in migraine? A patient's perspective.","authors":"Torres-Ferrus, Marta; Alpuente, Alicia; Pozo-Rosich, Patricia","year":2019,"journal":"Current opinion in neurology, 32(3), 395-404","doi":"10.1097/WCO.0000000000000689","pmid":"30950844","tags":[],"studyType":"review","evidenceStrength":"strong","keyFinding":"CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab, and eptinezumab) — the first migraine-specific preventive treatments — improve quality of life, reduce disability, and boost workplace productivity in migraine patients. Clinical trial data using patient-reported outcomes consistently showed improvements beyond just reducing headache days.\n\nAll four CGRP-mAbs achieved their primary endpoints of reducing monthly headache days and demonstrated meaningful impacts on daily functioning, global impression of change, and the overall burden of migraine on patients' lives.","whyItMatters":"Migraine affects hundreds of millions of people worldwide and is one of the leading causes of disability. Before CGRP-mAbs, preventive treatments were all repurposed from other conditions (blood pressure drugs, antidepressants, seizure medications) with significant side effects. These were the first drugs designed specifically for migraine prevention, and this review shows they improve not just headache frequency but the overall quality of patients' lives — a distinction that matters enormously for real-world patient care.","specificNumbers":"4 CGRP-mAbs reviewed: erenumab, fremanezumab, galcanezumab, eptinezumab · FDA and EMA approved · Improved: headache days, disability scores, QoL, workplace productivity, patient global impression","methodology":"Narrative review of clinical trial data for all four FDA/EMA-approved CGRP monoclonal antibodies, focusing on patient-reported outcomes including quality of life, disability measures, workplace productivity, and global impression of change. Reviewed data from trials in both episodic and chronic migraine populations.","limitations":"Based on clinical trial populations that may not fully represent real-world migraine patients. Patient-reported outcomes can be subjective and influenced by placebo effects. Long-term quality of life data beyond the trial periods was limited at the time of publication. Comparative effectiveness between the four CGRP-mAbs was not directly assessed."},{"rthcId":"RPEP-04523","title":"Lebetin 2, a Snake Venom-Derived B-Type Natriuretic Peptide, Provides Immediate and Prolonged Protection against Myocardial Ischemia-Reperfusion Injury via Modulation of Post-Ischemic Inflammatory Response.","authors":"Tourki, Bochra; Dumesnil, Anais; Belaidi, Elise; Ghrir, Slim; Godin-Ribuot, Diane; Marrakchi, Naziha; Richard, Vincent; Mulder, Paul; Messadi, Erij","year":2019,"journal":"Toxins, 11(9)","doi":"10.3390/toxins11090524","pmid":"31510060","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Both Lebetin 2 (L2) and BNP reduced infarct size, fibrosis, and inflammatory response after ischemia-reperfusion injury, with decreased leukocyte and proinflammatory M1 macrophage infiltration in the damaged area compared to untreated animals.\n\nCritically, only L2 increased anti-inflammatory M2-like macrophages in the injured tissue — a key distinction from BNP. L2 also uniquely promoted higher densities of endothelial cells and cardiomyocytes, suggesting enhanced tissue repair and blood vessel preservation. A single injection provided both acute and prolonged cardioprotective effects, mediated at least partly through modulation of the post-ischemic inflammatory response.","whyItMatters":"Heart attacks cause massive tissue damage partly through the inflammatory response that follows blood flow restoration. Current therapies focus on reopening blocked arteries but do little to manage this harmful inflammation. L2's ability to shift immune cells from a destructive (M1) to a healing (M2) state while preserving heart muscle and blood vessels represents a fundamentally different protective mechanism — one that could complement existing treatments and improve long-term outcomes after heart attack.","specificNumbers":"","methodology":"Mice underwent coronary artery ligation followed by reperfusion to model heart attack and ischemia-reperfusion injury. Animals received a single injection of either L2, BNP, or no treatment. Researchers measured infarct size, fibrosis, inflammatory cell infiltration (including M1 vs. M2 macrophage subsets), endothelial cell density, and cardiomyocyte density in the injured heart tissue. Results were compared across all treatment groups.","limitations":"This is a preclinical mouse study, and results may not translate directly to humans. Sample sizes were not specified in the abstract. The study used a single injection, so optimal dosing regimens for sustained protection are unknown. The exact mechanism by which L2 uniquely promotes M2 macrophage polarization was not fully elucidated. Long-term cardiac functional outcomes beyond the acute and subacute phases were not reported."},{"rthcId":"RPEP-04524","title":"Randomised clinical trial: a placebo-controlled study of subcutaneous or intradermal NEXVAX2, an investigational immunomodulatory peptide therapy for coeliac disease.","authors":"Truitt, Kenneth E; Daveson, A James M; Ee, Hooi C; Goel, Gautam; MacDougall, James; Neff, Kristin; Anderson, Robert P","year":2019,"journal":"Alimentary pharmacology & therapeutics, 50(5), 547-555","doi":"10.1111/apt.15435","pmid":"31407810","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04525","title":"Discovery of Functional Macrocyclic Peptides by Means of the RaPID System.","authors":"Tsiamantas, Christos; Otero-Ramirez, Manuel E; Suga, Hiroaki","year":2019,"journal":"Methods in molecular biology (Clifton, N.J.), 2001, 299-315","doi":"10.1007/978-1-4939-9504-2_14","pmid":"31134577","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04526","title":"Effects of an Extract of Salmon Milt on Symptoms and Serum TNF and Substance P in Patients With Fibromyalgia Syndrome.","authors":"Tsilioni, Irene; Pipis, Haralambos; Freitag, Manuela Sagrario Cabrera; Izquierdo, Maria Dolores Carrillo; Freitag, Karin; Theoharides, Theoharis C","year":2019,"journal":"Clinical therapeutics, 41(8), 1564-1574.e2","doi":"10.1016/j.clinthera.2019.05.019","pmid":"31303280","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04527","title":"Peptide-conjugate antisense based splice-correction for Duchenne muscular dystrophy and other neuromuscular diseases.","authors":"Tsoumpra, Maria K; Fukumoto, Seiji; Matsumoto, Toshio; Takeda, Shin'ichi; Wood, Matthew J A; Aoki, Yoshitsugu","year":2019,"journal":"EBioMedicine, 45, 630-645","doi":"10.1016/j.ebiom.2019.06.036","pmid":"31257147","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04528","title":"A phase I clinical study of a cocktail vaccine of Wilms' tumor 1 (WT1) HLA class I and II peptides for recurrent malignant glioma.","authors":"Tsuboi, Akihiro; Hashimoto, Naoya; Fujiki, Fumihiro; Morimoto, Soyoko; Kagawa, Naoki; Nakajima, Hiroko; Hosen, Naoki; Nishida, Sumiyuki; Nakata, Jun; Morita, Satoshi; Sakamoto, Junichi; Oji, Yusuke; Oka, Yoshihiro; Sugiyama, Haruo","year":2019,"journal":"Cancer immunology, immunotherapy : CII, 68(2), 331-340","doi":"10.1007/s00262-018-2274-1","pmid":"30430205","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The cocktail vaccine combining WT1 HLA class I and class II peptides was safe across all tested doses in patients with recurrent malignant glioma. No grade III/IV toxicity or dose-limiting toxicity was observed at any of the three dose levels of the class II peptide (0.75, 1.5, or 3 mg).\n\nAmong the 14 enrolled patients, 11 completed the initial 6-week vaccination course. Six of the 14 patients (43%) achieved stable disease at 6 weeks. The median overall survival was 24.7 weeks, with a 1-year survival rate of 36%.","whyItMatters":"Peptide-based cancer vaccines targeting tumor-associated proteins like WT1 represent a promising immunotherapy strategy. This trial demonstrated that combining class I and class II peptides — which activate different arms of the immune system — is safe, opening the door for larger efficacy trials. For patients with recurrent malignant glioma, who have very limited treatment options, this approach could eventually expand the therapeutic toolkit.","specificNumbers":"","methodology":"This was a Phase I clinical trial enrolling 14 patients with recurrent malignant glioma (2 grade 3 and 12 grade 4) who were HLA-A*24:02-positive. Patients received weekly alternating injections: one week a vaccine with 3 mg of WT1 HLA class I peptide alone, and the next week a cocktail combining the class I peptide with one of three escalating doses of the WT1 HLA class II peptide (0.75, 1.5, or 3 mg). After 6 weeks without significant adverse effects, vaccination continued at 2-4-week intervals. The primary endpoint was safety, with immunological responses and survival as secondary measures.","limitations":"This was a small Phase I trial focused primarily on safety, not efficacy, so the survival data should be interpreted cautiously. With only 14 patients and no control group, it is impossible to determine whether the vaccine improved outcomes compared to natural disease course. The study was also restricted to HLA-A*24:02-positive patients, limiting the applicability to a subset of the population. Three patients dropped out early due to disease progression, which may have biased the completion and response data."},{"rthcId":"RPEP-04529","title":"Adrenomedullin: Continuing to explore cardioprotection.","authors":"Tsuruda, Toshihiro; Kato, Johji; Kuwasako, Kenji; Kitamura, Kazuo","year":2019,"journal":"Peptides, 111, 47-54","doi":"10.1016/j.peptides.2018.03.012","pmid":"29577955","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04530","title":"Design and Synthetic Strategies for Helical Peptides.","authors":"Tu, Licheng; Wang, Dongyuan; Li, Zigang","year":2019,"journal":"Methods in molecular biology (Clifton, N.J.), 2001, 107-131","doi":"10.1007/978-1-4939-9504-2_7","pmid":"31134570","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04531","title":"PlantAFP: a curated database of plant-origin antifungal peptides.","authors":"Tyagi, Atul; Pankaj, Vaishali; Singh, Sanjay; Roy, Sudeep; Semwal, Manoj; Shasany, Ajit K; Sharma, Ashok","year":2019,"journal":"Amino acids, 51(10-12), 1561-1568","doi":"10.1007/s00726-019-02792-5","pmid":"31612325","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04532","title":"GHRH antagonists support lung endothelial barrier function.","authors":"Uddin, Mohammad A; Akhter, Mohammad S; Singh, Sitanshu S; Kubra, Khadeja-Tul; Schally, Andrew V; Jois, Seetharama; Barabutis, Nektarios","year":2019,"journal":"Tissue barriers, 7(4), 1669989","doi":"10.1080/21688370.2019.1669989","pmid":"31578921","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GHRH antagonist peptides protected lung endothelial barrier integrity by suppressing activation of MLC2, ERK1/2, and JAK2/STAT3 pathways while increasing P53 and pAMPK levels. In contrast, GHRH itself and the GHRH agonist MR409 disrupted endothelial barrier function through opposite effects on these pathways. Transendothelial resistance measurements confirmed that GHRH antagonists strengthened the barrier while GHRH and its agonists weakened it.","whyItMatters":"Acute Respiratory Distress Syndrome (ARDS) is a life-threatening condition where the lung's blood vessel barrier breaks down, flooding the lungs with fluid. This study reveals that GHRH peptide antagonists can protect this barrier through multiple anti-inflammatory pathways. Given the limited treatment options for ARDS, GHRH antagonist peptides could represent a new therapeutic approach for this lethal condition.","specificNumbers":"GHRH antagonists: suppressed MLC2, ERK1/2, JAK2/STAT3 · increased P53 and pAMPK · increased transendothelial resistance · GHRH and agonist MR409: opposite effects","methodology":"Researchers used bovine pulmonary arterial endothelial cells to study the effects of GHRH, GHRH agonists (MR409), and GHRH antagonists on intracellular signaling pathways. Protein activation was measured by Western blotting. Endothelial barrier function was assessed by transendothelial electrical resistance measurements.","limitations":"This is an in vitro study using bovine lung cells, and results may not translate directly to intact human lungs or clinical ARDS. Only one cell type was studied, and the complexity of ARDS involves multiple cell types and inflammatory cascades. Specific GHRH antagonist compounds used were not detailed in the abstract. No in vivo validation was provided."},{"rthcId":"RPEP-04533","title":"The nuclear concentration required for antisense oligonucleotide activity in myotonic dystrophy cells.","authors":"van der Bent, M Leontien; Paulino da Silva Filho, Omar; Willemse, Marieke; Hällbrink, Mattias; Wansink, Derick G; Brock, Roland","year":2019,"journal":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 33(10), 11314-11325","doi":"10.1096/fj.201900263R","pmid":"31311315","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Of two cell-penetrating peptides tested for delivering antisense oligonucleotides (ASOs) to myotonic dystrophy muscle cells, only PepFect14 (PF14) successfully delivered ASOs to the nucleus and corrected disease-typical abnormal splicing in a dose-dependent manner. Nona-arginine facilitated cellular uptake but failed to deliver ASOs to the nucleus. PF14 also protected ASOs from degradation. Nuclear ASO concentrations in the upper nanomolar range were required to dissolve MBNL1 protein foci — a hallmark of myotonic dystrophy type 1 (DM1).","whyItMatters":"Myotonic dystrophy type 1 is the most common adult muscular dystrophy, and ASOs targeting the disease-causing RNA expansion are a leading therapeutic approach. But getting ASOs into the nucleus where they need to work is a major delivery challenge. This study shows that the right cell-penetrating peptide (PF14) can solve this problem — not just getting cargo into cells, but specifically into the nucleus. It also establishes the critical concentration threshold needed for therapeutic effect.","specificNumbers":"Upper nanomolar nuclear concentration required · PF14 = successful nuclear delivery · Nona-arginine = failed nuclear delivery · Dose-dependent splicing correction · MBNL1 foci dissolution confirmed","methodology":"DM1 muscle cell model treated with ASOs complexed with either nona-arginine or PepFect14 cell-penetrating peptides. Therapeutic effect measured by correction of abnormal RNA splicing. Nuclear delivery confirmed by time-lapse confocal microscopy. ASO integrity assessed by fluorescence lifetime imaging (distinguishing intact ASO from degraded fluorophore). Nuclear concentration quantified by fluorescence correlation spectroscopy combined with immunofluorescence for MBNL1 foci.","limitations":"This is an in vitro cell culture study — the DM1 muscle cell model doesn't replicate the full complexity of muscle tissue in vivo. The nuclear concentration threshold (upper nanomolar) is measured in culture and may differ in living tissue where delivery barriers are more complex. PF14's performance in cell culture may not translate to systemic delivery in animals or humans."},{"rthcId":"RPEP-04534","title":"Antimicrobial Host Defence Peptides: Immunomodulatory Functions and Translational Prospects.","authors":"van der Does, Anne M; Hiemstra, Pieter S; Mookherjee, Neeloffer","year":2019,"journal":"Advances in experimental medicine and biology, 1117, 149-171","doi":"10.1007/978-981-13-3588-4_10","pmid":"30980358","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04535","title":"The Komodo dragon (Varanus komodoensis) genome and identification of innate immunity genes and clusters.","authors":"van Hoek, Monique L; Prickett, M Dennis; Settlage, Robert E; Kang, Lin; Michalak, Pawel; Vliet, Kent A; Bishop, Barney M","year":2019,"journal":"BMC genomics, 20(1), 684","doi":"10.1186/s12864-019-6029-y","pmid":"31470795","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04536","title":"Ralstonia eutropha, containing high poly-β-hydroxybutyrate levels, regulates the immune response in mussel larvae challenged with Vibrio coralliilyticus.","authors":"Van Hung, Nguyen; De Schryver, Peter; Dung, Nguyen Viet; Nevejan, Nancy; Bossier, Peter","year":2019,"journal":"Fish & shellfish immunology, 84, 196-203","doi":"10.1016/j.fsi.2018.09.066","pmid":"30266603","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04537","title":"Tuning the Binding Affinity and Selectivity of Perfluoroaryl-Stapled Peptides by Cysteine-Editing.","authors":"Verhoork, Sanne J M; Jennings, Claire E; Rozatian, Neshat; Reeks, Judith; Meng, Jieman; Corlett, Emily K; Bunglawala, Fazila; Noble, Martin E M; Leach, Andrew G; Coxon, Christopher R","year":2019,"journal":"Chemistry (Weinheim an der Bergstrasse, Germany), 25(1), 177-182","doi":"10.1002/chem.201804163","pmid":"30255959","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In stapled peptides targeting the p53-MDM2/MDMX interaction:\n\n- Replacing L-cysteine residues with 'cysteine analogues' of different stereochemistry (D vs. L), side chain length, and beta-carbon substitution produced significant changes in binding affinity and target selectivity\n- Some modifications, particularly incorporating two D-cysteine residues, favorably altered the positions of key functional amino acid side chains\n- Computationally constructed homology models correlated with experimental surface plasmon resonance (SPR) binding data\n- The approach demonstrates that the thiol-containing residue in cysteine-stapled peptides is not just a structural linker but actively influences target binding\n\nThis provides a new dimension for optimizing stapled peptide drug candidates beyond the staple chemistry itself.","whyItMatters":"The p53-MDM2 interaction is one of the most intensely pursued cancer drug targets — reactivating p53 could help treat over 50% of human cancers. Stapled peptides are among the most promising approaches, but optimizing their potency and selectivity has been challenging. This study reveals that a previously overlooked feature — the exact nature of the cysteine used for stapling — can dramatically tune drug properties. This gives medicinal chemists a new optimization tool that could accelerate the development of stapled peptide cancer therapeutics.","specificNumbers":"","methodology":"Researchers synthesized a series of perfluoroaryl-stapled peptides based on a p53-derived sequence with systematic variations in the cysteine residues used for cross-linking. Binding affinity to MDM2 and MDMX was measured by surface plasmon resonance (SPR). Target selectivity was assessed by comparing MDM2 vs. MDMX binding ratios. Computational homology modeling was used to rationalize the observed structure-activity relationships by predicting how cysteine modifications affected the positioning of functional amino acid side chains.","limitations":"The study focused on a single target system (p53-MDM2/MDMX), and the generalizability of cysteine-editing effects to other stapled peptide targets is unknown. Only in vitro binding data were generated — no cellular activity, permeability, or in vivo efficacy was assessed. The number of cysteine variants tested was limited; more extensive exploration could reveal additional useful modifications. The computational models provide rationalization but may not fully capture the dynamic behavior of these peptides in solution. Manufacturing feasibility of non-standard cysteine analogs at scale was not addressed."},{"rthcId":"RPEP-04538","title":"Ghrelin and aggressive behaviours-Evidence from preclinical and human genetic studies.","authors":"Vestlund, Jesper; Winsa-Jörnulf, Julia; Hovey, Daniel; Lundström, Sebastian; Lichtenstein, Paul; Anckarsäter, Henrik; Studer, Erik; Suchankova, Petra; Westberg, Lars; Jerlhag, Elisabet","year":2019,"journal":"Psychoneuroendocrinology, 104, 80-88","doi":"10.1016/j.psyneuen.2019.02.020","pmid":"30818255","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Central (intracerebroventricular) ghrelin infusion increased aggression in male mice using the resident-intruder test, while systemic ghrelin injection did not — indicating the effect requires direct brain action. Blocking the ghrelin receptor (GHSR-1A) with JMV2959 reduced aggression, and this anti-aggressive effect was abolished when brain serotonin was depleted. Ex vivo biochemical data pointed to serotonin in the amygdala as the key mediator. In a human genetic study of 784 young men, the Leu72Leu genotype of the pre-pro-ghrelin gene was associated with greater aggression specifically in those with hazardous alcohol use.","whyItMatters":"Aggression is a major public health concern, especially alcohol-fueled violence. Understanding the biological mechanisms behind aggressive behavior could lead to better prevention and treatment strategies. This study identifies the central ghrelin pathway — a peptide system already targeted by drugs for other conditions — as a modulator of aggression through serotonin signaling, opening potential pharmacological approaches to managing pathological aggression.","specificNumbers":"","methodology":"The study combined mouse behavioral experiments with human genetic analysis. In mice, central and peripheral ghrelin administration was tested alongside the GHSR-1A antagonist JMV2959 in the resident-intruder aggression paradigm. Serotonin depletion experiments tested whether the ghrelin-aggression link depended on serotonergic signaling. Ex vivo analysis measured serotonin, dopamine, and noradrenaline in the amygdala. The human component was a genetic association study in 784 young men from the general population, examining pre-pro-ghrelin gene variants in relation to self-reported antisocial behaviors and alcohol use.","limitations":"The mouse experiments used central ghrelin infusion, which doesn't reflect natural ghrelin signaling dynamics. The human genetic study was cross-sectional and observational, so it cannot prove the ghrelin variant causes aggression. Only males were studied in both the mouse and human components, limiting generalizability to females. The human aggression measure relied on self-reported antisocial behaviors rather than direct behavioral observation. The genetic association would need replication in independent cohorts."},{"rthcId":"RPEP-04539","title":"Peripheral Blood Mononuclear Cell Oxytocin and Vasopressin Receptor Expression Positively Correlates with Social and Behavioral Function in Children with Autism.","authors":"Voinsky, Irena; Bennuri, Sirish C; Svigals, Julie; Frye, Richard E; Rose, Shannon; Gurwitz, David","year":2019,"journal":"Scientific reports, 9(1), 13443","doi":"10.1038/s41598-019-49617-9","pmid":"31530830","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04540","title":"Natriuretic peptides in heart failure: Current achievements and future perspectives.","authors":"Volpe, Massimo; Battistoni, Allegra; Rubattu, Speranza","year":2019,"journal":"International journal of cardiology, 281, 186-189","doi":"10.1016/j.ijcard.2018.04.045","pmid":"30545616","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04541","title":"Thymosin Beta 4 Is Involved in the Development of Electroacupuncture Tolerance.","authors":"Wan, Juan; Ding, Yi; Nan, Sha; Zhang, Qiulin; Sun, Jinrui; Suo, Chuanguang; Ding, Mingxing","year":2019,"journal":"Frontiers in cellular neuroscience, 13, 75","doi":"10.3389/fncel.2019.00075","pmid":"30971892","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04542","title":"Cardiac Versus Renal Response to Volume Expansion in Preclinical Systolic Dysfunction With PDEV Inhibition and BNP.","authors":"Wan, Siu-Hin; Torres-Courchoud, Isabel; McKie, Paul M; Slusser, Joshua P; Redfield, Margaret M; Burnett, John C; Hodge, David O; Chen, Horng H","year":2019,"journal":"JACC. Basic to translational science, 4(8), 962-972","doi":"10.1016/j.jacbts.2019.08.008","pmid":"31909303","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04543","title":"The Relationship of Appetite-Regulating Hormones in the Development of Cardiac Cachexia.","authors":"Wang, Can; Dong, Xiaoying; Wei, Limu; Sun, Junfeng; Zhao, Fali; Meng, Choushuan; Wu, Dongdong; Wang, Ting; Fu, Lu","year":2019,"journal":"International heart journal, 60(2), 384-391","doi":"10.1536/ihj.18-131","pmid":"30799377","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04544","title":"Protective effect of peptide DR8 on bleomycin-induced pulmonary fibrosis by regulating the TGF-β/MAPK signaling pathway and oxidative stress.","authors":"Wang, Dan; Yan, Zhibin; Bu, Lili; An, Chunmei; Deng, Bochuan; Zhang, Jianfeng; Rao, Jing; Cheng, Lu; Zhang, Jingying; Zhang, Bangzhi; Xie, Junqiu","year":2019,"journal":"Toxicology and applied pharmacology, 382, 114703","doi":"10.1016/j.taap.2019.114703","pmid":"31398421","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04545","title":"Identifying the binding mechanism of LEAP2 to receptor GHSR1a.","authors":"Wang, Jia-Hui; Li, Hao-Zheng; Shao, Xiao-Xia; Nie, Wei-Han; Liu, Ya-Li; Xu, Zeng-Guang; Guo, Zhan-Yun","year":2019,"journal":"The FEBS journal, 286(7), 1332-1345","doi":"10.1111/febs.14763","pmid":"30666806","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The study revealed several key insights into LEAP2-GHSR1a binding:\n\n- LEAP2 and ghrelin bind GHSR1a competitively (sharing the same or overlapping binding sites), contrary to prior reports of non-competitive binding\n- LEAP2 shows dual antagonistic behavior depending on timing:\n  - Added before ghrelin: acts as a non-competitive antagonist (reduces maximal ghrelin effect)\n  - Added simultaneously with ghrelin: acts as a competitive antagonist (shifts the dose-response curve)\n- This unusual pharmacological profile is likely caused by LEAP2's slow dissociation rate from the receptor\n- The N-terminal fragment of LEAP2 is critical for receptor binding\n- These findings resolve conflicting reports in the literature about LEAP2's mechanism","whyItMatters":"The ghrelin-GHSR1a system is a major regulator of appetite, body weight, and growth hormone release. LEAP2 naturally counterbalances ghrelin's hunger-promoting effects. Understanding exactly how LEAP2 blocks this receptor could enable the design of new drugs for obesity and metabolic disorders that mimic or enhance LEAP2's action — potentially offering a different approach to weight management than current GLP-1 medications.","specificNumbers":"","methodology":"The researchers used cell-based binding assays (measuring competitive displacement of labeled ghrelin by LEAP2) and receptor activation assays (measuring calcium signaling through GHSR1a) in cultured cells. LEAP2 was added either before or simultaneously with ghrelin to characterize its antagonistic behavior. Truncated LEAP2 fragments were tested to identify which regions are required for receptor binding.","limitations":"This is an in vitro study using cell-based assays that may not fully reflect in vivo pharmacology. The slow dissociation rate hypothesis for LEAP2's dual behavior is proposed but not directly measured with kinetic binding studies. The study focuses on receptor binding and activation but does not assess downstream metabolic effects. The concentration ranges used in cell assays may not reflect physiological LEAP2 and ghrelin levels. No animal or human studies were conducted."},{"rthcId":"RPEP-04546","title":"Molecular design of sequence-minimized, structure-optimized, and hydrocarbon-stapled helix-helix interactions in the trimer-of-hairpins motif of pediatric pneumonia RSV-F protein.","authors":"Wang, Jihong; Zhang, Jingxiu; Sun, Xiangguo; Liu, Chengjun; Li, Xingli; Chen, Lei","year":2019,"journal":"Chemical biology & drug design, 94(1), 1292-1299","doi":"10.1111/cbdd.13501","pmid":"30776182","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04547","title":"Dietary gossypol reduced intestinal immunity and aggravated inflammation in on-growing grass carp (Ctenopharyngodon idella).","authors":"Wang, Kai-Zhuo; Feng, Lin; Jiang, Wei-Dan; Wu, Pei; Liu, Yang; Jiang, Jun; Kuang, Sheng-Yao; Tang, Ling; Zhang, Yong-An; Zhou, Xiao-Qiu","year":2019,"journal":"Fish & shellfish immunology, 86, 814-831","doi":"10.1016/j.fsi.2018.12.014","pmid":"30543935","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04548","title":"Design of a RADA16-based self-assembling peptide nanofiber scaffold for biomedical applications.","authors":"Wang, Rongrong; Wang, Zhaoyue; Guo, Yayuan; Li, Hongmin; Chen, Zhuoyue","year":2019,"journal":"Journal of biomaterials science. Polymer edition, 30(9), 713-736","doi":"10.1080/09205063.2019.1605868","pmid":"31018781","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04549","title":"Transcriptome analysis of the molecular mechanism underlying immunity- and reproduction trade-off in Locusta migratoria infected by Micrococcus luteus.","authors":"Wang, Shaohua; Liu, Xiaojun; Xia, Zhiyong; Xie, Guoqiang; Tang, Bin; Wang, Shigui","year":2019,"journal":"PloS one, 14(8), e0211605","doi":"10.1371/journal.pone.0211605","pmid":"31412031","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04550","title":"Development and application of a high-throughput liquid chromatography-tandem mass spectrometric method for the simultaneous determination of thymosin α1 and its recombinant human form in plasma and urine.","authors":"Wang, Tingting; Yin, Lei; Wang, Hao; Fawcett, John Paul; Gu, Jingkai","year":2019,"journal":"Journal of pharmaceutical and biomedical analysis, 170, 16-21","doi":"10.1016/j.jpba.2019.03.030","pmid":"30903925","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04551","title":"Ferritin nanoparticle-based SpyTag/SpyCatcher-enabled click vaccine for tumor immunotherapy.","authors":"Wang, Wenjun; Liu, Zhida; Zhou, Xiaoxiao; Guo, Zhenqian; Zhang, Jing; Zhu, Ping; Yao, Sheng; Zhu, Mingzhao","year":2019,"journal":"Nanomedicine : nanotechnology, biology, and medicine, 16, 69-78","doi":"10.1016/j.nano.2018.11.009","pmid":"30529790","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Ferritin nanoparticles modified with the SpyCatcher protein covalently linked to tumor-specific peptide antigens (via SpyTag) produced 2-3 fold enhanced cytotoxic T cell responses compared to soluble peptide antigens. The nanoparticles rapidly drained to lymph nodes and targeted dendritic cells (especially CD8α+ DCs). When carrying HPV16 E7 peptide or MC38 tumor neoantigen peptides, the vaccine significantly suppressed tumor growth, with further enhancement when combined with PD-1 checkpoint blockade.","whyItMatters":"Personalized cancer vaccines using tumor-specific peptide neoantigens are a promising frontier in oncology, but delivering multiple peptide antigens efficiently is challenging. This modular click-chemistry platform solves that problem — any peptide antigen tagged with SpyTag can be instantly loaded onto the nanoparticle, enabling rapid personalization for individual patients' tumors.","specificNumbers":"2-3 fold enhanced CTL response · HPV16 E7 and MC38 neoantigen peptides · rapid lymph node drainage · CD8α+ DC targeting · enhanced effect with PD-1 blockade","methodology":"SpyCatcher-modified ferritin nanoparticles were generated and conjugated with SpyTag-containing tumor peptide antigens via covalent click chemistry. Mice were immunized subcutaneously and assessed for lymph node drainage, dendritic cell targeting (flow cytometry), and cytotoxic T cell responses. Anti-tumor efficacy was tested in HPV16 E7 and MC38 tumor models, alone and in combination with PD-1 checkpoint blockade.","limitations":"Mouse tumor models only — human immune responses and tumor microenvironments differ significantly. The SpyTag/SpyCatcher system adds complexity to antigen preparation. Scalability for clinical manufacturing of personalized neoantigen vaccines is not addressed. Long-term immune memory and durability of anti-tumor responses were not reported."},{"rthcId":"RPEP-04552","title":"Ghrelin Aggravates Prostate Enlargement in Rats with Testosterone-Induced Benign Prostatic Hyperplasia, Stromal Cell Proliferation, and Smooth Muscle Contraction in Human Prostate Tissues.","authors":"Wang, Xiaolong; Wang, Yiming; Gratzke, Christian; Sterr, Christian; Yu, Qingfeng; Li, Bingsheng; Strittmatter, Frank; Herlemann, Annika; Tamalunas, Alexander; Rutz, Beata; Ciotkowska, Anna; Waidelich, Raphaela; Liu, Chunxiao; Stief, Christian G; Hennenberg, Martin","year":2019,"journal":"Oxidative medicine and cellular longevity, 2019, 4748312","doi":"10.1155/2019/4748312","pmid":"31885795","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04553","title":"The regulation of crecropin-A and gloverin 2 by the silkworm Toll-like gene 18 wheeler in immune response.","authors":"Wang, Xue-Yang; Li, Tao; Johannes, Mapuranga; Xu, Jia-Ping; Sun, Xia; Qin, Sheng; Xu, Ping-Zhen; Li, Mu-Wang; Wu, Yang-Chun","year":2019,"journal":"Journal of invertebrate pathology, 164, 49-58","doi":"10.1016/j.jip.2019.04.006","pmid":"31026465","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04554","title":"TAT peptide-modified cisplatin-loaded iron oxide nanoparticles for reversing cisplatin-resistant nasopharyngeal carcinoma.","authors":"Weng, Huanhuan; Bejjanki, Naveen Kumar; Zhang, Juan; Miao, Xiangwan; Zhong, Ying; Li, Hailiang; Xie, Huifen; Wang, Siqi; Li, Quanming; Xie, Minqiang","year":2019,"journal":"Biochemical and biophysical research communications, 511(3), 597-603","doi":"10.1016/j.bbrc.2019.02.117","pmid":"30826059","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"TAT peptide-modified cisplatin-loaded iron oxide nanoparticles (TAT-SPION-CDDP) reversed cisplatin resistance in two nasopharyngeal carcinoma cell lines. The IC50 decreased by an average of 85% in HNE-1/DDP cells and 94% in CNE-2/DDP cells compared to cisplatin alone.\n\nThe dual mechanism combined the Fenton reaction from iron oxide (generating reactive oxygen species) with enhanced cellular uptake via the TAT peptide (YGRKKRRQRRR). TAT modification significantly improved intracellular nanoparticle delivery, enabling lower therapeutic doses and potentially reduced side effects.","whyItMatters":"Drug resistance is a major reason chemotherapy fails in nasopharyngeal carcinoma and other cancers. This nanoparticle system attacks resistance through two mechanisms simultaneously — the Fenton reaction from iron oxide creates oxidative stress that cisplatin-resistant cells aren't adapted to, while the TAT peptide forces more drug into cells. Reducing the effective cisplatin dose by 85–94% could dramatically decrease the severe side effects that limit treatment.","specificNumbers":"","methodology":"Researchers synthesized superparamagnetic iron oxide nanoparticles (SPIONs) loaded with cisplatin and surface-modified with the TAT cell-penetrating peptide. The nanoparticles were tested on cisplatin-resistant nasopharyngeal carcinoma cell lines (HNE-1/DDP and CNE-2/DDP) and their sensitive parent lines. Cell viability assays measured IC50 values. Cisplatin was fluorescently labeled to track intracellular uptake and study the delivery mechanism. The study compared free cisplatin, unmodified SPION-CDDP, and TAT-modified SPION-CDDP.","limitations":"This is entirely an in vitro study using cancer cell lines, not animal models or human patients. Cell line results frequently do not predict in vivo efficacy due to differences in tumor microenvironment, immune system interactions, and pharmacokinetics. The TAT peptide is not cell-specific, so in vivo use would require additional targeting strategies to avoid delivering cisplatin to healthy tissues. Long-term stability, toxicity, and biodistribution of these nanoparticles were not assessed. The mechanism of resistance reversal through the Fenton reaction needs further validation."},{"rthcId":"RPEP-04555","title":"Discovery of Potent, Selective, and Short-Acting Peptidic V2 Receptor Agonists.","authors":"Wiśniewski, Kazimierz; Qi, Steve; Kraus, John; Ly, Brian; Srinivasan, Karthik; Tariga, Hiroe; Croston, Glenn; La, Erin; Wiśniewska, Halina; Ortiz, Carlos; Laporte, Régent; Rivière, Pierre J-M; Neyer, Gebhard; Hargrove, Diane M; Schteingart, Claudio D","year":2019,"journal":"Journal of medicinal chemistry, 62(10), 4991-5005","doi":"10.1021/acs.jmedchem.9b00132","pmid":"31022340","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04556","title":"The antinociceptive effects and molecular mechanisms of ghrelin(1-7)-NH2 at the supraspinal level in acute pain in mice.","authors":"Wu, Bing; Liu, Yongling; Liu, Fuyan; Deng, Qing; Wang, Jinglei; Han, Renwen; Zhang, Dalei; Chen, Jiaxiang; Wei, Jie","year":2019,"journal":"Brain research bulletin, 146, 112-123","doi":"10.1016/j.brainresbull.2018.12.016","pmid":"30599218","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04557","title":"Echinacoside Isolated from Cistanche tubulosa Putatively Stimulates Growth Hormone Secretion via Activation of the Ghrelin Receptor.","authors":"Wu, Chieh-Ju; Chien, Mei-Yin; Lin, Nan-Hei; Lin, Yi-Chiao; Chen, Wen-Ying; Chen, Chao-Hsiang; Tzen, Jason T C","year":2019,"journal":"Molecules (Basel, Switzerland), 24(4)","doi":"10.3390/molecules24040720","pmid":"30781558","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04558","title":"Vasoactive intestinal peptide-induced tolerogenic dendritic cells attenuated arthritis in experimental collagen-induced arthritic mice.","authors":"Wu, Huaxiang; Shen, Jingfang; Liu, Lei; Lu, Xiaoyong; Xue, Jing","year":2019,"journal":"International journal of rheumatic diseases, 22(7), 1255-1262","doi":"10.1111/1756-185X.13578","pmid":"31062502","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"VIP-treated dendritic cells (VIP-DC) showed reduced expression of immune activation markers (MHC II, CD40, CD86), decreased interferon-gamma production, and increased IL-4 production compared to untreated dendritic cells (P < 0.05 or 0.01).\n\nWhen administered to mice with established collagen-induced arthritis, VIP-DC decreased clinical arthritis scores and reduced both bone erosion (P < 0.05) and inflammation (P < 0.01) compared to untreated dendritic cells. VIP-DC performed comparably to Bay 11-7082-induced tolerogenic dendritic cells but showed potentially superior bone protection.","whyItMatters":"Rheumatoid arthritis treatments often suppress the entire immune system, increasing infection risk. This study explores a more targeted approach — using a natural peptide (VIP) to reprogram specific immune cells into anti-inflammatory agents that can be delivered as a cell therapy. If translatable to humans, this could provide joint protection with fewer systemic side effects than current immunosuppressive drugs.","specificNumbers":"","methodology":"Mouse bone marrow cells were differentiated into dendritic cells using GM-CSF and IL-4, then treated with either VIP (40 ng/mL) or Bay 11-7082 (0.5 μg/mL) to induce tolerance. Cell surface markers and cytokine production were measured by flow cytometry and ELISA. The tolerogenic dendritic cells were then injected intraperitoneally into DBA mice with collagen-induced arthritis on day 40 (after arthritis onset). Treatment effects were assessed by clinical arthritis scoring and pathological examination of synovial hyperplasia, pannus formation, inflammation, and bone erosion.","limitations":"This is an animal study using the collagen-induced arthritis model in mice, which doesn't perfectly replicate human rheumatoid arthritis. The study examined treatment started after arthritis onset, but follow-up duration and long-term outcomes were not detailed. The mechanism by which VIP-DC protect bone more effectively than Bay-DC was not fully elucidated. Sample sizes for the mouse experiments were not specified in the abstract."},{"rthcId":"RPEP-04559","title":"Recent Progress in Machine Learning-based Prediction of Peptide Activity for Drug Discovery.","authors":"Wu, Qihui; Ke, Hanzhong; Li, Dongli; Wang, Qi; Fang, Jiansong; Zhou, Jingwei","year":2019,"journal":"Current topics in medicinal chemistry, 19(1), 4-16","doi":"10.2174/1568026619666190122151634","pmid":"30674262","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04560","title":"Mitochondria-targeted antioxidant peptide SS-31 mediates neuroprotection in a rat experimental glaucoma model.","authors":"Wu, Xiaoqiong; Pang, Yu; Zhang, Zhilin; Li, Xiabin; Wang, Chao; Lei, Yingqing; Li, Ailing; Yu, Ling; Ye, Jian","year":2019,"journal":"Acta biochimica et biophysica Sinica, 51(4), 411-421","doi":"10.1093/abbs/gmz020","pmid":"30811524","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04561","title":"CgSOCS6 negatively regulates the expression of CgIL17s and CgDefh1 in the pacific oyster Crassostrea gigas.","authors":"Wu, Zhaojun; Sun, Jiejie; Wang, Liyan; Zong, Yanan; Han, Zirong; Yang, Wen; Liu, Zhaoqun; Wang, Lingling; Song, Linsheng","year":2019,"journal":"Fish & shellfish immunology, 93, 1084-1092","doi":"10.1016/j.fsi.2019.08.055","pmid":"31449980","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04562","title":"Antibodies and venom peptides: new modalities for ion channels.","authors":"Wulff, Heike; Christophersen, Palle; Colussi, Paul; Chandy, K George; Yarov-Yarovoy, Vladimir","year":2019,"journal":"Nature reviews. Drug discovery, 18(5), 339-357","doi":"10.1038/s41573-019-0013-8","pmid":"30728472","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04563","title":"A pan-coronavirus fusion inhibitor targeting the HR1 domain of human coronavirus spike.","authors":"Xia, Shuai; Yan, Lijue; Xu, Wei; Agrawal, Anurodh S; Algaissi, Abdullah; Tseng, Chien-Te K; Wang, Qian; Du, Lanying; Tan, Wenjie; Wilson, Ian A; Jiang, Shibo; Yang, Bin; Lu, Lu","year":2019,"journal":"Science advances, 5(4), eaav4580","doi":"10.1126/sciadv.aav4580","pmid":"30880857","tags":["antiviral-peptides","fusion-inhibitors"],"studyType":"Preclinical Study (In Vitro + Animal Model)","evidenceStrength":"moderate","keyFinding":"Researchers developed a peptide called EK1 that blocks all human coronaviruses from entering cells by targeting a conserved region (HR1 domain) of the spike protein. EK1 inhibited fusion and cell entry of every human coronavirus tested, with IC50 values of 0.19–0.62 μM — meaning it worked at very low concentrations.\n\nIn mice, EK1 protected against HCoV-OC43 infection and provided long-term protection. Crystal structures confirmed the peptide forms stable complexes with HR1 domains from multiple divergent coronaviruses, explaining its broad-spectrum activity.","whyItMatters":"This study was published in April 2019 — months before SARS-CoV-2 emerged. It demonstrated that a single peptide could block all known human coronaviruses, essentially predicting the need for pan-coronavirus therapeutics. The EK1 peptide and its derivatives became immediately relevant when COVID-19 struck, and this work laid the groundwork for pandemic-preparedness research using peptide fusion inhibitors.","specificNumbers":"IC50: 0.19–0.62 μM across all HCoVs · protected mice from HCoV-OC43 · long-term in vivo protection · crystal structures resolved · targets conserved HR1 domain","methodology":"The researchers designed peptides based on the HR2 domains of various human coronaviruses, then tested them for fusion inhibition against a panel of HCoVs in cell culture. The lead peptide EK1 was optimized for potency. In vivo efficacy was tested in mice infected with HCoV-OC43. Crystal structures of EK1 bound to HR1 domains from different coronaviruses were solved to understand the structural basis of broad-spectrum activity.","limitations":"Only tested in mice (HCoV-OC43 model), not in humans or non-human primates. The study predates SARS-CoV-2, so efficacy against COVID-19 was not tested (though it was later shown to work against SARS-CoV-2). Peptide drugs face pharmacokinetic challenges including short half-life and poor oral bioavailability. Manufacturing scale-up for pandemic use was not addressed."},{"rthcId":"RPEP-04564","title":"Mutant neuropeptide S receptor reduces sleep duration with preserved memory consolidation.","authors":"Xing, Lijuan; Shi, Guangsen; Mostovoy, Yulia; Gentry, Nicholas W; Fan, Zenghua; McMahon, Thomas B; Kwok, Pui-Yan; Jones, Christopher R; Ptáček, Louis J; Fu, Ying-Hui","year":2019,"journal":"Science translational medicine, 11(514)","doi":"10.1126/scitranslmed.aax2014","pmid":"31619542","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A missense mutation in the neuropeptide S receptor 1 (NPSR1) gene was identified in humans who naturally sleep less than average. When this mutation was engineered into mice, they also slept less despite having higher sleep pressure — and remarkably, they were resistant to the memory problems that normally accompany sleep deprivation. The mutant receptor showed increased sensitivity to neuropeptide S activation in vivo, suggesting the NPS/NPSR1 signaling pathway plays a critical role in regulating both sleep duration and the link between sleep and memory.","whyItMatters":"Most people who sleep less suffer cognitive consequences, but a small number of 'natural short sleepers' function perfectly well on fewer hours. This study identified a specific neuropeptide receptor mutation behind this trait, revealing a biological pathway that could one day be targeted to help people maintain cognitive function under sleep restriction — with potential applications for shift workers, military personnel, and people with sleep disorders.","specificNumbers":"","methodology":"The researchers identified the NPSR1 mutation through genetic analysis of families with natural short sleep phenotypes. They then created mice carrying the equivalent mutation and measured their sleep duration, sleep pressure, and memory performance using contextual memory tests after sleep deprivation. Receptor sensitivity was assessed by measuring responses to exogenous neuropeptide S administration in vivo.","limitations":"The mutation was identified in a small number of human families, so its prevalence and effects across diverse populations are unknown. Mouse models may not fully recapitulate human sleep regulation. The study does not address long-term health consequences of reduced sleep in carriers of this mutation, and the mechanism by which the mutant receptor preserves memory consolidation despite less sleep is not fully explained."},{"rthcId":"RPEP-04565","title":"Targeting surface nucleolin induces autophagy-dependent cell death in pancreatic cancer via AMPK activation.","authors":"Xu, Cheng; Wang, Yunfei; Tu, Qiu; Zhang, Zhiye; Chen, Mengrou; Mwangi, James; Li, Yaxiong; Jin, Yang; Zhao, Xudong; Lai, Ren","year":2019,"journal":"Oncogene, 38(11), 1832-1844","doi":"10.1038/s41388-018-0556-x","pmid":"30356139","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04566","title":"Safety and tolerability of calcitonin-gene-related peptide binding monoclonal antibodies for the prevention of episodic migraine - a meta-analysis of randomized controlled trials.","authors":"Xu, Da; Chen, Deng; Zhu, Li-Na; Tan, Ge; Wang, Hai-Jiao; Zhang, Yu; Liu, Ling","year":2019,"journal":"Cephalalgia : an international journal of headache, 39(9), 1164-1179","doi":"10.1177/0333102419829007","pmid":"30789292","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04567","title":"Human Enteric Defensin 5 Promotes Shigella Infection of Macrophages.","authors":"Xu, Dan; Liao, Chongbing; Xiao, Jiu; Fang, Kun; Zhang, Wei; Yuan, Weirong; Lu, Wuyuan","year":2019,"journal":"Infection and immunity, 88(1)","doi":"10.1128/IAI.00769-19","pmid":"31611271","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04568","title":"Peripheral and central substance P expression in rat CFA-induced TMJ synovitis pain.","authors":"Xu, Liqin; Jiang, Henghua; Feng, Yaping; Cao, Pinyin; Ke, Jin; Long, Xing","year":2019,"journal":"Molecular pain, 15, 1744806919866340","doi":"10.1177/1744806919866340","pmid":"31322474","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04569","title":"Hydroxyapatite Nanoparticle-Crosslinked Peptide Hydrogels for Three-Dimensional Culture and Differentiation of MC3T3-E1 Osteoblasts.","authors":"Xu, Yingjie; Wu, Xin; Wang, Shuyi; Yang, Changzhou; Li, Ying; Cao, Yi","year":2019,"journal":"Journal of biomedical nanotechnology, 15(12), 2351-2362","doi":"10.1166/jbn.2019.2856","pmid":"31748016","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04570","title":"AJICAP: Affinity Peptide Mediated Regiodivergent Functionalization of Native Antibodies.","authors":"Yamada, Kei; Shikida, Natsuki; Shimbo, Kazutaka; Ito, Yuji; Khedri, Zahra; Matsuda, Yutaka; Mendelsohn, Brian A","year":2019,"journal":"Angewandte Chemie (International ed. in English), 58(17), 5592-5597","doi":"10.1002/anie.201814215","pmid":"30854738","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The AJICAP method used Fc-binding affinity peptide reagents to introduce thiol functional groups onto three specific lysine residues in native IgG antibodies — without any genetic engineering or antibody modification. A cytotoxic drug was then chemically linked to these thiol groups to create an antibody-drug conjugate.\n\nThe resulting HER2-targeting ADC demonstrated selective binding to HER2-positive cells (confirmed by surface plasmon resonance) and effectively killed HER2-positive tumors in an in vivo xenograft mouse model. The method provides site-specific drug attachment starting from any native antibody.","whyItMatters":"ADCs are one of the fastest-growing sectors in oncology drug development, but most require expensive and time-consuming antibody engineering to attach drugs at specific sites. AJICAP bypasses this by using peptides to direct drug attachment on native, unmodified antibodies. This could dramatically simplify and accelerate ADC development, potentially enabling any antibody to be converted into an ADC without genetic modification.","specificNumbers":"","methodology":"Fc affinity peptide reagents were designed to bind the Fc region of native IgG antibodies and introduce reactive thiol groups at three lysine positions. Cytotoxic drug molecules were conjugated via the thiol groups. Binding specificity was confirmed by surface plasmon resonance. Anticancer efficacy was tested in vitro against HER2-positive cells and in vivo using a xenograft mouse tumor model.","limitations":"The study demonstrated proof-of-concept with a single HER2-targeting ADC. Drug-to-antibody ratio control and consistency across different antibody types were not extensively characterized. The long-term stability and pharmacokinetics of AJICAP-produced ADCs in comparison to engineered site-specific ADCs are not reported. Only one cytotoxic payload was tested. Manufacturing scalability and regulatory pathway considerations are not discussed."},{"rthcId":"RPEP-04571","title":"Protective Effect of Thymosin β4 against Abdominal Aortic Ischemia-Reperfusion-Induced Acute Lung Injury in Rats.","authors":"Yaman, Onur M; Guner, Ibrahim; Guntas, Gulcan; Sonmez, Osman Fuat; Tanriverdi, Gamze; Cakiris, Aris; Aksu, Ugur; Akyol, Sibel; Guzel, Elif; Uzun, Hafize; Yelmen, Nermin; Sahin, Gulderen","year":2019,"journal":"Medicina (Kaunas, Lithuania), 55(5)","doi":"10.3390/medicina55050187","pmid":"31121838","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04572","title":"Neuropeptides Substance P and Calcitonin Gene Related Peptide Accelerate the Development and Fibrogenesis of Endometriosis.","authors":"Yan, Dingmin; Liu, Xishi; Guo, Sun-Wei","year":2019,"journal":"Scientific reports, 9(1), 2698","doi":"10.1038/s41598-019-39170-w","pmid":"30804432","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Substance P (SP) and calcitonin gene-related peptide (CGRP), acting through their receptors NK1R and CRLR/RAMP-1, induced a cascade of cellular transformations in endometriotic tissue: epithelial-mesenchymal transition (EMT), fibroblast-to-myofibroblast transdifferentiation (FMT), and conversion of stromal cells into smooth muscle cells.\n\nThis cascade resulted in increased cell migration, invasiveness, contractility, collagen production, and ultimately fibrosis. Neutralizing NK1R and/or CGRP/CRLR/RAMP-1 signaling abrogated these processes. Deep endometriosis lesions showed significantly higher nerve fiber density, receptor expression, and fibrotic content than ovarian endometriomas, with fibrosis extent correlating positively with receptor staining levels and nerve fiber density.","whyItMatters":"Endometriosis affects roughly 10% of women of reproductive age and current treatments are limited. This study reveals that sensory nerves don't just transmit pain — they actively drive disease progression through neuropeptide signaling. This opens the door to targeting substance P and CGRP receptors as a therapeutic strategy, potentially treating both the pain and the underlying tissue damage of endometriosis.","specificNumbers":"","methodology":"Researchers used cultured endometriotic stromal cells treated with substance P, CGRP, or rat dorsal root ganglia supernatant to study cellular transformations in vitro. They also performed immunohistochemistry on human endometriosis lesion samples comparing deep endometriosis to ovarian endometriomas, measuring nerve fiber density, receptor expression, and fibrotic markers including α-SMA, desmin, and smooth muscle myosin heavy-chain.","limitations":"The in vitro cell culture experiments may not fully replicate the complex microenvironment of endometriosis in vivo. The human tissue analysis was observational and correlational — it shows association between nerve density and fibrosis but doesn't prove causation in living patients. No clinical intervention was tested, so it remains unknown whether blocking these receptors would reduce fibrosis in patients with endometriosis."},{"rthcId":"RPEP-04573","title":"Thymosin β4: potential to treat epidermolysis bullosa and other severe dermal injuries.","authors":"Yang, Won S; Kang, Shinwook; Sung, Jihye; Kleinman, Hynda K","year":2019,"journal":"European journal of dermatology : EJD, 29(5), 459-467","doi":"10.1684/ejd.2019.3642","pmid":"31649007","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04574","title":"Preparation and Characterization of Gelatin and Antioxidant Peptides from Gelatin Hydrolysate of Skipjack Tuna (Katsuwonus pelamis) Bone Stimulated by in vitro Gastrointestinal Digestion.","authors":"Yang, Xiu-Rong; Zhao, Yu-Qin; Qiu, Yi-Ting; Chi, Chang-Feng; Wang, Bin","year":2019,"journal":"Marine drugs, 17(2)","doi":"10.3390/md17020078","pmid":"30678362","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04575","title":"Cell-penetrating peptide-modified quantum dots as a ratiometric nanobiosensor for the simultaneous sensing and imaging of lysosomes and extracellular pH.","authors":"Yang, Yan; Xia, Mengchan; Zhang, Sichun; Zhang, Xinrong","year":2019,"journal":"Chemical communications (Cambridge, England), 56(1), 145-148","doi":"10.1039/c9cc07596h","pmid":"31799976","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04576","title":"Molecular characterization and immune analysis of a defensin from small abalone, Haliotis diversicolor.","authors":"Yao, Tuo; Lu, Jie; Ye, Lingtong; Wang, Jiangyong","year":2019,"journal":"Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology, 235, 1-7","doi":"10.1016/j.cbpb.2019.05.004","pmid":"31078702","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04577","title":"Exendin-4 from Heloderma suspectum venom: From discovery to its latest application as type II diabetes combatant.","authors":"Yap, Michelle Khai Khun; Misuan, Nurhamimah","year":2019,"journal":"Basic & clinical pharmacology & toxicology, 124(5), 513-527","doi":"10.1111/bcpt.13169","pmid":"30417596","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Exendin-4, a 39-amino acid peptide discovered in Gila monster (Heloderma suspectum) venom, is a full agonist of the GLP-1 receptor with a longer half-life than endogenous GLP-1 due to resistance to DPP-4 enzymatic degradation. Its helical region interacts with the GLP-1 receptor's extracellular N-terminal domain while its C-terminal tryptophan cage enhances binding affinity, switching the receptor from auto-inhibited to auto-activated state. Beyond blood glucose lowering through enhanced β-cell function and GLP-1 receptor upregulation, exendin-4 has shown benefits for neuropathy, nephropathy, and ventricular remodeling. While it has reasonable subcutaneous bioavailability, its half-life remains relatively short, prompting ongoing modifications to improve pharmacokinetics and potency.","whyItMatters":"Exendin-4 is the natural peptide that gave rise to exenatide (Byetta), the first GLP-1 receptor agonist drug approved for type 2 diabetes. Its discovery from lizard venom is one of the most celebrated examples of venom-derived drug development and laid the foundation for the entire GLP-1 agonist drug class — now one of the most impactful classes of medications in modern medicine, including semaglutide (Ozempic/Wegovy).","specificNumbers":"39 amino acids · Full GLP-1 receptor agonist · Longer half-life than endogenous GLP-1 · Benefits beyond glucose: neuropathy, nephropathy, cardiac remodeling","methodology":"Narrative review covering the discovery, pharmacology, structure-function relationships, clinical trial evidence, and ongoing modifications of exendin-4 as a GLP-1 receptor agonist for type 2 diabetes treatment.","limitations":"As a narrative review, this paper synthesizes existing literature rather than presenting new data. The review was published in 2019, before the widespread clinical use of newer GLP-1 agonists like semaglutide and tirzepatide, so it does not cover the latest developments in the field."},{"rthcId":"RPEP-04578","title":"Tumor targeting and microenvironment-responsive multifunctional fusion protein for pro-apoptotic peptide delivery.","authors":"Yin, Jun; Liu, Dingkang; Bao, Lichen; Wang, Qun; Chen, Ye; Hou, Shan; Yue, Yali; Yao, Wenbing; Gao, Xiangdong","year":2019,"journal":"Cancer letters, 452, 38-50","doi":"10.1016/j.canlet.2019.03.016","pmid":"30904618","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04579","title":"Enhanced Intracellular Delivery of BCG Cell Wall Skeleton into Bladder Cancer Cells Using Liposomes Functionalized with Folic Acid and Pep-1 Peptide.","authors":"Yoon, Ho Yub; Yang, Hee Mang; Kim, Chang Hyun; Goo, Yoon Tae; Hwang, Gwang Yong; Chang, In Ho; Whang, Young Mi; Choi, Young Wook","year":2019,"journal":"Pharmaceutics, 11(12)","doi":"10.3390/pharmaceutics11120652","pmid":"31817179","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04580","title":"Fighting Type-2 Diabetes: Present and Future Perspectives.","authors":"Yu, Cai-Guo; Fu, Ying; Fang, Yuan; Zhang, Ning; Sun, Rong-Xin; Zhao, Dong; Feng, Ying-Mei; Zhang, Bao-Yu","year":2019,"journal":"Current medicinal chemistry, 26(10), 1891-1907","doi":"10.2174/0929867324666171009115356","pmid":"28990512","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04581","title":"Targeting CGRP for the Prevention of Migraine and Cluster Headache: A Narrative Review.","authors":"Yuan, Hsiangkuo; Spare, Nicole M; Silberstein, Stephen D","year":2019,"journal":"Headache, 59 Suppl 2, 20-32","doi":"10.1111/head.13583","pmid":"31291020","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04582","title":"Identification of Novel Autoantibodies Associated With Psoriatic Arthritis.","authors":"Yuan, Yulin; Qiu, Jingyi; Lin, Zuan-Tao; Li, Wen; Haley, Christopher; Mui, Uyen Ngoc; Ning, Jing; Tyring, Stephen K; Wu, Tianfu","year":2019,"journal":"Arthritis & rheumatology (Hoboken, N.J.), 71(6), 941-951","doi":"10.1002/art.40830","pmid":"30618213","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04583","title":"Gastric ulcer induced changes in substance P and Nk1, Nk2, Nk3 receptors expression in different stomach localizations with regard to intrinsic neuronal system.","authors":"Zalecki, Michal","year":2019,"journal":"Histochemistry and cell biology, 151(1), 29-42","doi":"10.1007/s00418-018-1715-4","pmid":"30155561","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04584","title":"A microbial-based cancer vaccine for induction of EGFRvIII-specific CD8+ T cells and anti-tumor immunity.","authors":"Zebertavage, Lauren; Bambina, Shelly; Shugart, Jessica; Alice, Alejandro; Zens, Kyra D; Lauer, Peter; Hanson, Bill; Gough, Michael J; Crittenden, Marka R; Bahjat, Keith S","year":2019,"journal":"PloS one, 14(1), e0209153","doi":"10.1371/journal.pone.0209153","pmid":"30601871","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04585","title":"Optimization of a multivalent peptide vaccine for nicotine addiction.","authors":"Zeigler, David F; Roque, Richard; Clegg, Christopher H","year":2019,"journal":"Vaccine, 37(12), 1584-1590","doi":"10.1016/j.vaccine.2019.02.003","pmid":"30772068","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04586","title":"Comparison of the Effects of Glucagon-Like Peptide Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors for Prevention of Major Adverse Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus.","authors":"Zelniker, Thomas A; Wiviott, Stephen D; Raz, Itamar; Im, KyungAh; Goodrich, Erica L; Furtado, Remo H M; Bonaca, Marc P; Mosenzon, Ofri; Kato, Eri T; Cahn, Avivit; Bhatt, Deepak L; Leiter, Lawrence A; McGuire, Darren K; Wilding, John P H; Sabatine, Marc S","year":2019,"journal":"Circulation, 139(17), 2022-2031","doi":"10.1161/CIRCULATIONAHA.118.038868","pmid":"30786725","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04587","title":"Ligation of Soluble but Unreactive Peptide Segments in the Chemical Synthesis of Haemophilus Influenzae DNA Ligase.","authors":"Zhang, Baochang; Deng, Qiang; Zuo, Chong; Yan, Bingjia; Zuo, Chao; Cao, Xiu-Xiu; Zhu, Ting F; Zheng, Ji-Shen; Liu, Lei","year":2019,"journal":"Angewandte Chemie (International ed. in English), 58(35), 12231-12237","doi":"10.1002/anie.201905149","pmid":"31250514","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04588","title":"Growth Hormone-Releasing Hormone Receptor Antagonist Modulates Lung Inflammation and Fibrosis due to Bleomycin.","authors":"Zhang, Chongxu; Cai, Renzhi; Lazerson, Aaron; Delcroix, Gaetan; Wangpaichitr, Medhi; Mirsaeidi, Mehdi; Griswold, Anthony J; Schally, Andrew V; Jackson, Robert M","year":2019,"journal":"Lung, 197(5), 541-549","doi":"10.1007/s00408-019-00257-w","pmid":"31392398","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04589","title":"Naja atra venom peptide reduces pain by selectively blocking the voltage-gated sodium channel Nav1.8.","authors":"Zhang, Fan; Zhang, Changxin; Xu, Xunxun; Zhang, Yunxiao; Gong, Xue; Yang, Zuqin; Zhang, Heng; Tang, Dongfang; Liang, Songping; Liu, Zhonghua","year":2019,"journal":"The Journal of biological chemistry, 294(18), 7324-7334","doi":"10.1074/jbc.RA118.007370","pmid":"30804211","tags":["venom-derived-peptides"],"studyType":"preclinical-discovery","evidenceStrength":"moderate","keyFinding":"A 62-amino-acid peptide (μ-EPTX-Na1a) isolated from Chinese cobra venom selectively blocks the Nav1.8 sodium channel — a key pain-signaling channel in peripheral nerves — through a mechanism never seen before in any other toxin. In rodent models of both inflammatory and neuropathic pain, this peptide relieved pain more potently than morphine.\n\nCritically, μ-EPTX-Na1a showed no evident cytotoxicity, no cardiotoxicity, and no obvious adverse effects even at 30 times the analgesic dose, suggesting a wide safety margin compared to current painkillers.","whyItMatters":"The opioid crisis has created an urgent need for effective painkillers that don't carry addiction risk. Nav1.8 is expressed almost exclusively on pain-sensing nerves, making it an ideal target — blocking it should reduce pain without the euphoria, respiratory depression, or addiction associated with opioids. Finding a venom-derived peptide that's more potent than morphine, highly selective for Nav1.8, and safe at 30x the effective dose is a significant step toward non-addictive pain medicine.","specificNumbers":"62-amino-acid peptide · selective for Nav1.8 over other sodium channels · more potent than morphine · safe at 30× analgesic dose · no cytotoxicity or cardiotoxicity","methodology":"Large-scale screening of animal-derived toxins and venoms for Nav1.8 inhibitors. The identified peptide was purified from Naja atra venom and characterized using whole-cell voltage-clamp electrophysiology. Analgesic efficacy was tested in rodent models of inflammatory and neuropathic pain, with morphine as the comparator. Safety was assessed through cytotoxicity, cardiotoxicity, and high-dose adverse effect testing in mice.","limitations":"All testing was in rodents and cell lines — human clinical trials have not been conducted. The peptide's pharmacokinetics (how long it lasts in the body, how it's cleared) are not detailed. As a 62-amino-acid peptide, it would likely need injection rather than oral delivery. Manufacturing costs and scalability of venom-derived peptides can be challenging."},{"rthcId":"RPEP-04590","title":"Eight Collagen Peptides from Hydrolysate Fraction of Spanish Mackerel Skins: Isolation, Identification, and In Vitro Antioxidant Activity Evaluation.","authors":"Zhang, Jing-Bo; Zhao, Yu-Qin; Wang, Yu-Mei; Chi, Chang-Feng; Wang, Bin","year":2019,"journal":"Marine drugs, 17(4)","doi":"10.3390/md17040224","pmid":"31013895","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04591","title":"Prospective, double blinded, comparative assessment of the pharmacological activity of Cerebrolysin and distinct peptide preparations for the treatment of embolic stroke.","authors":"Zhang, Li; Chopp, Michael; Wang, Chunyang; Zhang, Yi; Lu, Mei; Zhang, Talan; Zhang, Zheng Gang","year":2019,"journal":"Journal of the neurological sciences, 398, 22-26","doi":"10.1016/j.jns.2019.01.017","pmid":"30665068","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04592","title":"Age-Related Loss of Innate Immune Antimicrobial Function of Dermal Fat Is Mediated by Transforming Growth Factor Beta.","authors":"Zhang, Ling-Juan; Chen, Stella Xiang; Guerrero-Juarez, Christian F; Li, Fengwu; Tong, Yun; Liang, Yuqiong; Liggins, Marc; Chen, Xu; Chen, Hao; Li, Min; Hata, Tissa; Zheng, Ye; Plikus, Maksim V; Gallo, Richard L","year":2019,"journal":"Immunity, 50(1), 121-136.e5","doi":"10.1016/j.immuni.2018.11.003","pmid":"30594464","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04593","title":"Type1 Interferons Potential Initiating Factors Linking Skin Wounds With Psoriasis Pathogenesis.","authors":"Zhang, Ling-Juan","year":2019,"journal":"Frontiers in immunology, 10, 1440","doi":"10.3389/fimmu.2019.01440","pmid":"31293591","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04594","title":"Genome-wide analysis of the ovodefensin gene family: Monophyletic origin, independent gene duplication and presence of different selection patterns.","authors":"Zhang, Long; Chen, Dongmei; Yu, Lintian; Wei, Yi; Li, Juan; Zhou, Caiquan","year":2019,"journal":"Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases, 68, 265-272","doi":"10.1016/j.meegid.2019.01.001","pmid":"30611743","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04595","title":"MiR-34b/c-5p and the neurokinin-1 receptor regulate breast cancer cell proliferation and apoptosis.","authors":"Zhang, Lufang; Wang, Lushan; Dong, Dong; Wang, Zhiyong; Ji, Wei; Yu, Man; Zhang, Fei; Niu, Ruifang; Zhou, Yunli","year":2019,"journal":"Cell proliferation, 52(1), e12527","doi":"10.1111/cpr.12527","pmid":"30334298","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The study established a direct regulatory link between miR-34b/c-5p and NK1R in breast cancer. Key findings across multiple approaches:\n\n- miR-34b/c-5p and truncated NK1R expression in 50 breast cancer patients correlated with tumor stage and Ki67 (proliferation marker)\n- Overexpressing miR-34b/c-5p or silencing NK1R suppressed proliferation, induced G2/M arrest, and triggered apoptosis in MDA-MB-231 and MCF-7 breast cancer cells\n- The NK1R antagonist aprepitant produced similar anti-cancer effects\n- Substance P (the endogenous NK1R agonist) rescued cell growth when miR-34b/c-5p was overexpressed or NK1R was silenced, confirming pathway specificity\n- In vivo xenograft models confirmed that miR-34b/c-5p overexpression or NK1R silencing reduced tumorigenicity","whyItMatters":"Aprepitant is already an FDA-approved drug (used for chemotherapy-induced nausea), and this study provides mechanistic evidence that it could be repurposed for breast cancer treatment. The substance P/NK1R pathway is increasingly recognized as a cancer driver across multiple tumor types, and this study provides both the molecular mechanism (via miR-34b/c-5p regulation) and clinical correlation data to support therapeutic targeting.","specificNumbers":"","methodology":"The researchers used multiple breast cancer cell lines (MDA-MB-231, MCF-7, T47D, SK-BR-3) and HEK-293T cells. NK1R regulation by miR-34 was confirmed by Western blot, qRT-PCR, and luciferase assays. Clinical correlation was assessed in 50 breast cancer patient samples. Cell proliferation was measured by CCK-8 and colony formation assays; apoptosis and cell cycle by flow cytometry. Cells were transfected with miR-34b/c-5p mimics or NK1R-siRNA, with or without substance P treatment or aprepitant. In vivo validation used BALB/c nude mouse xenograft models.","limitations":"The clinical correlation was based on only 50 patient samples, which limits statistical power. The in vivo studies used immunocompromised nude mice with xenograft tumors, which don't replicate human immune responses to cancer. Aprepitant's anti-cancer doses may differ from its approved anti-nausea doses, and therapeutic window in breast cancer patients is unknown. The study did not assess whether aprepitant interferes with standard breast cancer chemotherapy."},{"rthcId":"RPEP-04596","title":"β-Glucan from Saccharomyces cerevisiae induces SBD-1 production in ovine ruminal epithelial cells via the Dectin-1-Syk-NF-κB signaling pathway.","authors":"Zhang, Man; Jin, Xin; Yang, Yin-Feng","year":2019,"journal":"Cellular signalling, 53, 304-315","doi":"10.1016/j.cellsig.2018.10.018","pmid":"30401641","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04597","title":"Polypeptide-engineered DNA tetrahedrons for targeting treatment of colorectal cancer via apoptosis and autophagy.","authors":"Zhang, Nan; Yang, Yanan; Wang, Ziyi; Yang, Jing; Chu, Xiao; Liu, Jin; Zhao, Yongxing","year":2019,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 309, 48-58","doi":"10.1016/j.jconrel.2019.07.012","pmid":"31301339","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04598","title":"Dual-Functional Liposomes with Carbonic Anhydrase IX Antibody and BR2 Peptide Modification Effectively Improve Intracellular Delivery of Cantharidin to Treat Orthotopic Hepatocellular Carcinoma Mice.","authors":"Zhang, Xue; Lin, Congcong; Chan, Waikei; Liu, Kanglun; Lu, Aiping; Lin, Ge; Hu, Rong; Shi, Hongcan; Zhang, Hongqi; Yang, Zhijun","year":2019,"journal":"Molecules (Basel, Switzerland), 24(18)","doi":"10.3390/molecules24183332","pmid":"31547459","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04599","title":"Activation of mitogen-activated protein kinases in satellite glial cells of the trigeminal ganglion contributes to substance P-mediated inflammatory pain.","authors":"Zhang, Yanyan; Song, Ning; Liu, Fei; Lin, Jiu; Liu, Mengke; Huang, Chaolan; Liao, Daqing; Zhou, Cheng; Wang, Hang; Shen, Jiefei","year":2019,"journal":"International journal of oral science, 11(3), 24","doi":"10.1038/s41368-019-0055-0","pmid":"31501412","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04600","title":"Docking Flexible Cyclic Peptides with AutoDock CrankPep.","authors":"Zhang, Yuqi; Sanner, Michel F","year":2019,"journal":"Journal of chemical theory and computation, 15(10), 5161-5168","doi":"10.1021/acs.jctc.9b00557","pmid":"31505931","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04601","title":"Effects of thymosin β4 on neuronal apoptosis in a rat model of cerebral ischemia‑reperfusion injury.","authors":"Zhang, Zhongsheng; Liu, Shuangfeng; Huang, Sichun","year":2019,"journal":"Molecular medicine reports, 20(5), 4186-4192","doi":"10.3892/mmr.2019.10683","pmid":"31545437","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 48 rats divided into sham, ischemia/reperfusion (I/R), and Tβ4 treatment groups (n=16 each):\n\n- Tβ4-treated rats had significantly lower Zea-Longa neurological deficit scores compared to I/R controls\n- Tβ4 significantly reduced neuronal apoptosis (TUNEL-positive cells) compared to I/R group\n- Tβ4 significantly increased GRP78 expression (a protective endoplasmic reticulum chaperone)\n- Tβ4 significantly decreased CHOP and caspase-12 expression (pro-apoptotic ER stress markers)\n- These changes indicate Tβ4 protects neurons by modulating the endoplasmic reticulum stress response pathway","whyItMatters":"Stroke is a leading cause of death and disability worldwide, and current treatments have narrow time windows. Thymosin β4's ability to reduce brain damage after ischemia/reperfusion injury through the ER stress pathway could lead to a neuroprotective treatment that extends the therapeutic window for stroke patients.","specificNumbers":"","methodology":"Forty-eight Sprague-Dawley rats were divided into three groups. Focal cerebral ischemia/reperfusion was induced by blocking the right middle cerebral artery for 2 hours followed by 24 hours of reperfusion. Neurological deficits were scored, infarct volume was measured by TTC staining, apoptosis was detected by TUNEL assay, and GRP78, CHOP, and caspase-12 protein levels were assessed by immunohistochemistry and Western blot.","limitations":"The study used a standard rat stroke model which may not fully replicate human stroke complexity. Only 24-hour reperfusion was assessed — longer-term outcomes are unknown. The dose and timing of Tβ4 administration weren't detailed in the abstract. No behavioral or cognitive recovery testing beyond neurological deficit scoring was performed. No human clinical trials for Tβ4 in stroke exist."},{"rthcId":"RPEP-04602","title":"Phytic acid disrupted intestinal immune status and suppressed growth performance in on-growing grass carp (Ctenopharyngodon idella).","authors":"Zhong, Jing-Ren; Feng, Lin; Jiang, Wei-Dan; Wu, Pei; Liu, Yang; Jiang, Jun; Kuang, Sheng-Yao; Tang, Ling; Zhou, Xiao-Qiu","year":2019,"journal":"Fish & shellfish immunology, 92, 536-551","doi":"10.1016/j.fsi.2019.06.045","pmid":"31247320","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04603","title":"Dynamic Ghrelin and GH serum levels during combined simultaneous arginine clonidine stimulation test in children with dwarfism.","authors":"Zhou, Guangzhong; Du, Rongzeng","year":2019,"journal":"Italian journal of pediatrics, 45(1), 17","doi":"10.1186/s13052-019-0610-5","pmid":"30691498","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04604","title":"A β-defensin gene of Trachinotus ovatus might be involved in the antimicrobial and antiviral immune response.","authors":"Zhou, Yongcan; Lei, Yang; Cao, Zhenjie; Chen, Xiaojuan; Sun, Yun; Xu, Yue; Guo, Weiliang; Wang, Shifeng; Liu, Chunsheng","year":2019,"journal":"Developmental and comparative immunology, 92, 105-115","doi":"10.1016/j.dci.2018.11.011","pmid":"30448509","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04605","title":"Linezolid and Rifampicin Combination to Combat cfr-Positive Multidrug-Resistant MRSA in Murine Models of Bacteremia and Skin and Skin Structure Infection.","authors":"Zhou, Yu-Feng; Li, Liang; Tao, Meng-Ting; Sun, Jian; Liao, Xiao-Ping; Liu, Ya-Hong; Xiong, Yan Q","year":2019,"journal":"Frontiers in microbiology, 10, 3080","doi":"10.3389/fmicb.2019.03080","pmid":"31993042","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04606","title":"DNA-Encoded Macrocyclic Peptide Library.","authors":"Zhu, Zhengrong; Shaginian, Alex; Grady, La Shadric C; Davie, Christopher P; Lind, Kenneth; Pal, Sandeep; Thansandote, Praew; Simpson, Graham L","year":2019,"journal":"Methods in molecular biology (Clifton, N.J.), 2001, 273-284","doi":"10.1007/978-1-4939-9504-2_12","pmid":"31134575","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04607","title":"Substance P and pain chronicity.","authors":"Zieglgänsberger, W","year":2019,"journal":"Cell and tissue research, 375(1), 227-241","doi":"10.1007/s00441-018-2922-y","pmid":"30284083","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04608","title":"Mitochondrial-derived peptide humanin as therapeutic target in cancer and degenerative diseases.","authors":"Zuccato, Camila Florencia; Asad, Antonela Sofia; Nicola Candia, Alejandro Javier; Gottardo, María Florencia; Moreno Ayala, Mariela Alejandra; Theas, María Susana; Seilicovich, Adriana; Candolfi, Marianela","year":2019,"journal":"Expert opinion on therapeutic targets, 23(2), 117-126","doi":"10.1080/14728222.2019.1559300","pmid":"30582721","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04609","title":"iDEF-PseRAAC: Identifying the Defensin Peptide by Using Reduced Amino Acid Composition Descriptor.","authors":"Zuo, Yongchun; Chang, Yu; Huang, Shenghui; Zheng, Lei; Yang, Lei; Cao, Guifang","year":2019,"journal":"Evolutionary bioinformatics online, 15, 1176934319867088","doi":"10.1177/1176934319867088","pmid":"31391777","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04610","title":"Human β-defensin 1 in follicular fluid and semen: impact on fertility.","authors":"Zupin, Luisa; Polesello, Vania; Martinelli, Monica; Luppi, Stefania; Giolo, Elena; Zito, Gabriella; Romano, Federico; Segat, Ludovica; Crovella, Sergio; Ricci, Giuseppe","year":2019,"journal":"Journal of assisted reproduction and genetics, 36(4), 787-797","doi":"10.1007/s10815-019-01409-w","pmid":"30712073","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04611","title":"Campbell 2020 Suvorexant Fentanyl Self Administration","authors":"","year":2020,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04612","title":"Dean 2020 Multi Analyte Ptsd Biomarker Panel","authors":"","year":2020,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04613","title":"Demanelis 2020 Tissue Telomere Variation","authors":"","year":2020,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04614","title":"Khavinson 2020 Aedg Peptide Epitalon Stimulates","authors":"","year":2020,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04615","title":"Liu 2020 Thymalfasin Critical Covid19 Wuhan","authors":"","year":2020,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04616","title":"Murphy 2020 Ukbiobank Igf1 Cancer","authors":"","year":2020,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04617","title":"Vasconcelos 2020 Corticotropinreleasing Factor Receptor Sign","authors":"","year":2020,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04618","title":"Curli-Mediated Self-Assembly of a Fibrous Protein Scaffold for Hydroxyapatite Mineralization.","authors":"Abdali, Zahra; Aminzare, Masoud; Zhu, Xiaodan; DeBenedictis, Elizabeth; Xie, Oliver; Keten, Sinan; Dorval Courchesne, Noémie-Manuelle","year":2020,"journal":"ACS synthetic biology, 9(12), 3334-3343","doi":"10.1021/acssynbio.0c00415","pmid":"33237760","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04619","title":"Relative quantification of human β‑defensins gene expression in pterygium and normal conjunctiva samples.","authors":"Abubakar, Sa'adatu Aliyu; Isa, Muhammad Mohd; Omar, Nazri; Tan, Sheau Wei","year":2020,"journal":"Molecular medicine reports, 22(6), 4931-4937","doi":"10.3892/mmr.2020.11560","pmid":"33174018","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04620","title":"Characterization of casein-derived peptide bioactivity: Differential effects on angiotensin-converting enzyme inhibition and cytokine and nitric oxide production.","authors":"Adams, C; Sawh, F; Green-Johnson, J M; Jones Taggart, H; Strap, J L","year":2020,"journal":"Journal of dairy science, 103(7), 5805-5815","doi":"10.3168/jds.2019-17976","pmid":"32448573","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04621","title":"Interactions of GF-17 derived from LL-37 antimicrobial peptide with bacterial membranes: a molecular dynamics simulation study.","authors":"Aghazadeh, Hossein; Ganjali Koli, Mokhtar; Ranjbar, Reza; Pooshang Bagheri, Kamran","year":2020,"journal":"Journal of computer-aided molecular design, 34(12), 1261-1273","doi":"10.1007/s10822-020-00348-4","pmid":"33009624","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Molecular dynamics simulations revealed that GF-17 penetrated pure DPPG membranes (mimicking negatively charged bacterial surfaces) more favorably than mixed DPPE/DPPG membranes. The potential of mean force (PMF) calculation showed no energy barrier for GF-17 crossing through the center of the DPPG bilayer — meaning the peptide encounters no thermodynamic resistance when penetrating bacterial membranes.\n\nThe peptide increased the area per lipid and lateral diffusion of lipids (indicating membrane disruption and increased fluidity) but did not significantly affect bilayer thickness. GF-17 adopted a more compact and rigid structure in pure DPPG membranes compared to mixed membranes. The dominant secondary structures were α-helix and coil in both membrane types.","whyItMatters":"Antimicrobial resistance is one of the greatest threats to global health, and antimicrobial peptides like LL-37 derivatives represent a promising alternative to conventional antibiotics. Understanding exactly how these peptides penetrate and disrupt bacterial membranes at the atomic level is essential for designing more potent versions with fewer side effects. The finding that GF-17 faces no energy barrier when entering bacterial membranes provides a design principle — future antimicrobial peptides could be engineered to exploit this barrier-free mechanism.","specificNumbers":"","methodology":"Two independent molecular dynamics simulations were performed, each with four GF-17 peptide units interacting with model membranes: one composed of a 9:1 mixture of DPPE:DPPG lipids and one of pure DPPG lipids. Multiple membrane properties were analyzed, including mass density distributions, area per lipid, bilayer thickness, and lateral diffusion. The potential of mean force method calculated the free energy profile for peptide transfer from water into each membrane type. Peptide structure was assessed through radius of gyration, root mean square fluctuation, and secondary structure analysis.","limitations":"Molecular dynamics simulations, while powerful, use simplified models of biological membranes that may not capture the full complexity of real bacterial surfaces (which contain proteins, lipopolysaccharides, and other components). The simulation timescales are limited and may not capture all relevant dynamic processes. Model membranes lack the heterogeneity of actual bacterial membranes. The findings have not been validated with complementary experimental techniques. The anticancer activity mentioned in the introduction was not investigated in this study."},{"rthcId":"RPEP-04622","title":"Superoxide Dismutase 3 Inhibits LL-37/KLK-5-Mediated Skin Inflammation through Modulation of EGFR and Associated Inflammatory Cascades.","authors":"Agrahari, Gaurav; Sah, Shyam Kishor; Nguyen, Cuong Thach; Choi, Sung Sik; Kim, Hae-Young; Kim, Tae-Yoon","year":2020,"journal":"The Journal of investigative dermatology, 140(3), 656-665.e8","doi":"10.1016/j.jid.2019.08.434","pmid":"31465746","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04623","title":"Collagen Hydrolysates for Skin Protection: Oral Administration and Topical Formulation.","authors":"Aguirre-Cruz, Gabriel; León-López, Arely; Cruz-Gómez, Verónica; Jiménez-Alvarado, Rubén; Aguirre-Álvarez, Gabriel","year":2020,"journal":"Antioxidants (Basel, Switzerland), 9(2)","doi":"10.3390/antiox9020181","pmid":"32098294","tags":[],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Hydrolyzed collagen (HC) — collagen broken down into small peptides — shows dual benefits for skin when taken orally or applied topically. Oral ingestion increases collagen-derived peptide levels in the blood and improves measurable skin properties including elasticity, moisture retention, and transepidermal water loss. Daily oral HC intake also protects against UV-induced melasma, boosts fibroblast production, and enhances the skin's extracellular matrix.\n\nTopically, HC works as a safe cosmetic ingredient with effective moisturizing properties at the outermost skin layer (stratum corneum), reducing visible signs of aging like dryness, laxity, and wrinkles. The antioxidant activity of collagen peptides depends on their size — smaller peptides have greater free radical scavenging ability — and is driven by hydrophobic and aromatic amino acids in the peptide chain.","whyItMatters":"Collagen supplements are among the most popular peptide products on the consumer market, but the science behind them has often been dismissed as marketing hype. This review consolidates evidence showing measurable biological effects from both oral and topical collagen peptides, providing a scientific basis for their widespread use. The finding that peptide size matters for antioxidant activity also has practical implications for how collagen products should be formulated.","specificNumbers":"Lower molecular weight = greater antioxidant activity · Oral HC increases blood collagen peptide levels · Improvements in elasticity, moisture, transepidermal water loss · UV melasma protection observed · Fibroblast production enhanced","methodology":"This is a narrative review examining published research on hydrolyzed collagen for skin protection. The authors compared evidence for both oral supplementation and topical application, covering antioxidant mechanisms, bioavailability, and measurable skin outcomes from clinical and preclinical studies.","limitations":"As a narrative review, the paper doesn't use systematic review methodology or meta-analysis, so the strength of evidence isn't formally quantified. The exact antioxidant mechanisms of collagen peptides remain unclear. Many collagen skin studies have small sample sizes, short durations, and potential conflicts of interest from supplement manufacturers. The review doesn't clearly separate evidence quality between different claims."},{"rthcId":"RPEP-04624","title":"NO mediates the effect of the synthetic natriuretic peptide NPCdc on kidney and aorta in nephrectomised rats.","authors":"Aires, Regina S; Vieira, Leucio D; Freitas, Ana C N; de Lima, Maria E; Lima, Natalia K S; Farias, Juliane S; Paixão, Ana D","year":2020,"journal":"European journal of pharmacology, 866, 172780","doi":"10.1016/j.ejphar.2019.172780","pmid":"31734277","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The synthetic natriuretic peptide NPCdc, derived from rattlesnake venom, decreased mean arterial pressure and NADPH oxidase activity while increasing glomerular filtration rate, fractional sodium excretion, and nitric oxide levels in both control and nephrectomized rats. These effects were mediated through nitric oxide and components of natriuretic peptide receptor C (NPR-C) signaling, specifically involving ERK1/2 phosphorylation at Thr-202/Tyr-204.\n\nThe peptide was infused at 7.5 μg/kg/min for 70 minutes, producing beneficial cardiovascular and renal effects even in rats with reduced kidney mass (5/6 nephrectomy), suggesting potential therapeutic application for cardiorenal syndrome.","whyItMatters":"Cardiorenal syndrome — where heart and kidney failure worsen each other — is a major clinical challenge with limited treatment options. This venom-derived synthetic peptide simultaneously lowered blood pressure and improved kidney filtration, addressing both the cardiovascular and renal components. Its novel mechanism through NPR-C signaling, rather than the conventional natriuretic peptide receptors A and B, opens a new therapeutic pathway.","specificNumbers":"7.5 μg/kg/min dose · 70 min infusion · 70% structural homology with human natriuretic peptides · 5/6 nephrectomy model","methodology":"Anesthetized Wistar rats were divided into sham-operated controls and 5/6 nephrectomy groups. Each group received either saline or NPCdc infusion at 7.5 μg/kg/min for 70 minutes. Researchers measured arterial pressure, glomerular filtration rate, sodium excretion, nitric oxide levels, NADPH oxidase activity, and phosphorylation of several signaling proteins.","limitations":"This was an animal study in anesthetized rats, so results may not directly translate to humans. The acute 70-minute infusion does not reveal long-term effects or safety. The 5/6 nephrectomy model simulates chronic kidney disease but does not fully replicate human cardiorenal syndrome."},{"rthcId":"RPEP-04625","title":"Efficacy of immunotherapy targeting the neoantigen derived from epidermal growth factor receptor T790M/C797S mutation in non-small cell lung cancer.","authors":"Akazawa, Yu; Saito, Yuki; Yoshikawa, Toshiaki; Saito, Keigo; Nosaka, Kazuto; Shimomura, Manami; Mizuno, Shoichi; Nakamoto, Yasunari; Nakatsura, Tetsuya","year":2020,"journal":"Cancer science, 111(8), 2736-2746","doi":"10.1111/cas.14451","pmid":"32391625","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04626","title":"Comparison of Neurokinin A, Substance P, Interleukin 8, and Matrix Metalloproteinase-8 Changes in Pulp tissue and Gingival Crevicular Fluid Samples of Healthy and Symptomatic Irreversible Pulpitis Teeth.","authors":"Akbal Dincer, Gozde; Erdemir, Ali; Kisa, Ucler","year":2020,"journal":"Journal of endodontics, 46(10), 1428-1437","doi":"10.1016/j.joen.2020.07.013","pmid":"32702349","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"All four mediators (NKA, SP, IL-8, MMP-8) were significantly higher in pulpitis pulp tissue compared to healthy pulp (NKA: P<0.001, SP: P=0.005, IL-8: P<0.001, MMP-8: P<0.001). The same pattern was seen in gingival crevicular fluid (NKA: P=0.01, SP: P<0.001, IL-8: P=0.001, MMP-8: P<0.001). One week after root canal treatment, all mediator levels decreased significantly in GCF. SP, IL-8, and MMP-8 levels were higher in patients with higher pain scores than those with lower pain scores.","whyItMatters":"Understanding which molecular signals drive tooth pain has implications for developing targeted pain treatments. Substance P and neurokinin A are well-known pain and inflammation neuropeptides, and their elevation in pulpitis confirms their role in dental pain. The finding that gum fluid levels reflect pulp inflammation opens the possibility of non-invasive diagnostic testing — potentially detecting pulp disease through a simple gum fluid sample rather than requiring invasive pulp access.","specificNumbers":"","methodology":"Clinical study of 40 patients — 20 with healthy teeth and 20 with symptomatic irreversible pulpitis. Pulp tissue and gingival crevicular fluid (GCF) samples were collected from both groups. GCF sampling was repeated one week after root canal treatment. NKA, SP, IL-8, and MMP-8 levels were measured by ELISA. GCF from contralateral healthy teeth served as controls. Statistical analysis included t-tests, ANOVA, Kruskal-Wallis, Mann-Whitney U, and Pearson correlation.","limitations":"Relatively small sample size (40 patients). The study measured associations between peptide levels and inflammation/pain but cannot establish causation. Pain scoring is subjective and variable between patients. GCF collection technique can affect sample quality. Only a one-week follow-up after treatment was included. The study did not test whether blocking these neuropeptides would reduce dental pain."},{"rthcId":"RPEP-04627","title":"Monoclonal antibodies as a preventive therapy for migraine: A meta-analysis.","authors":"Alasad, Yousef Waleed; Asha, Mohammad Zaki","year":2020,"journal":"Clinical neurology and neurosurgery, 195, 105900","doi":"10.1016/j.clineuro.2020.105900","pmid":"32460120","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"All three CGRP monoclonal antibodies significantly reduced monthly migraine days compared to placebo at every time point measured: by 2.07 days at 4 weeks, 1.78 days at 8 weeks, and 1.80 days at 12 weeks (all p<0.001). These effects were consistent across erenumab 70 mg, fremanezumab 225 mg, and galcanezumab 120 mg individually.\n\nBeyond migraine day reduction, patients on active treatment used fewer acute migraine medications and had significantly higher rates of achieving a 50% or greater reduction in migraine frequency. Treatment-related adverse events showed no significant difference between active treatment and placebo groups.","whyItMatters":"Before CGRP antibodies arrived, migraine prevention relied on medications originally designed for other conditions — blood pressure drugs, antidepressants, and anti-seizure medications — all with significant side effects. This meta-analysis confirmed that targeting the CGRP peptide pathway directly provides consistent migraine relief with a clean safety profile, validating an entirely new class of peptide-based preventive therapy.","specificNumbers":"","methodology":"This was a systematic review and meta-analysis of double-blind, placebo-controlled randomized clinical trials. Researchers searched for studies evaluating monthly subcutaneous injections of CGRP monoclonal antibodies in patients with chronic or episodic migraine. They analyzed 13 eligible RCTs encompassing 6,979 patients (about 85% female), comparing changes in monthly migraine days, acute medication use, 50% responder rates, and treatment-related adverse events.","limitations":"The analysis only included trials using monthly subcutaneous dosing at specific doses, so results may not apply to other dosing regimens (e.g., quarterly eptinezumab infusions, which had no eligible studies). Most participants were female (~85%), reflecting migraine epidemiology but limiting generalizability to males. The longest follow-up was 12 weeks, so longer-term efficacy and safety are not captured. Publication bias and heterogeneity between trials are inherent limitations of any meta-analysis."},{"rthcId":"RPEP-04628","title":"Antimicrobial peptides as an argument for the involvement of innate immunity in psoriasis (Review).","authors":"Alecu, Mihail; Coman, Gabriela; Mușetescu, Alina; Coman, Oana Andreia","year":2020,"journal":"Experimental and therapeutic medicine, 20(6), 192","doi":"10.3892/etm.2020.9322","pmid":"33101482","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04629","title":"Safety and Tolerability of 3 CGRP Monoclonal Antibodies in Practice: A Retrospective Cohort Study.","authors":"Alex, Ashley; Vaughn, Caila; Rayhill, Melissa","year":2020,"journal":"Headache, 60(10), 2454-2462","doi":"10.1111/head.13956","pmid":"32969035","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04630","title":"Copper(II) and Amylin Analogues: A Complicated Relationship.","authors":"Alghrably, Mawadda; Dudek, Dorota; Emwas, Abdul-Hamid; Jaremko, Łukasz; Jaremko, Mariusz; Rowińska-Żyrek, Magdalena","year":2020,"journal":"Inorganic chemistry, 59(4), 2527-2535","doi":"10.1021/acs.inorgchem.9b03498","pmid":"32027132","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04631","title":"Series of Novel and Highly Potent Cyclic Peptide PCSK9 Inhibitors Derived from an mRNA Display Screen and Optimized via Structure-Based Design.","authors":"Alleyne, Candice; Amin, Rupesh P; Bhatt, Bhavana; Bianchi, Elisabetta; Blain, J Craig; Boyer, Nicolas; Branca, Danila; Embrey, Mark W; Ha, Sookhee N; Jette, Kelli; Johns, Douglas G; Kerekes, Angela D; Koeplinger, Kenneth A; LaPlaca, Derek; Li, Nianyu; Murphy, Beth; Orth, Peter; Ricardo, Alonso; Salowe, Scott; Seyb, Kathleen; Shahripour, Aurash; Stringer, Joseph R; Sun, Yili; Tracy, Rodger; Wu, Chengwei; Xiong, Yusheng; Youm, Hyewon; Zokian, Hratch J; Tucker, Thomas J","year":2020,"journal":"Journal of medicinal chemistry, 63(22), 13796-13824","doi":"10.1021/acs.jmedchem.0c01084","pmid":"33170686","tags":["pcsk9-inhibitors","cyclic-peptides"],"studyType":"preclinical-drug-development","evidenceStrength":"preliminary","keyFinding":"Researchers used mRNA display screening to discover a new series of cyclic peptides that block the interaction between PCSK9 and the LDL receptor — the same target hit by existing injectable antibody drugs like evolocumab and alirocumab. Through structure-based drug design, they optimized these peptides into smaller, more metabolically stable bicyclic compounds (such as compound 78) that could potentially be developed into oral, once-daily PCSK9 inhibitors for lowering cholesterol.","whyItMatters":"Current PCSK9 inhibitors are highly effective at lowering LDL cholesterol but require injection every 2-4 weeks, which limits their adoption. An oral peptide PCSK9 inhibitor taken once daily could dramatically expand access to this class of cardiovascular drugs, making potent cholesterol-lowering therapy as simple as taking a pill.","specificNumbers":"","methodology":"The team used mRNA display — a technique where trillions of peptide sequences are screened simultaneously — to identify initial hit compounds that block the PCSK9/LDLR protein-protein interaction. They then used X-ray crystallography and structure-activity relationship studies to systematically optimize these peptides, reducing molecular weight and improving metabolic stability while maintaining potency. Testing included cell-based assays and animal models (mice, rats, and cynomolgus monkeys).","limitations":"This is a drug discovery paper focused on chemical optimization — no human efficacy or safety data exist for these compounds. The transition from potent lab compounds to successful oral drugs faces many hurdles including bioavailability, manufacturing, and clinical trial outcomes. Specific in vivo efficacy data for the lead compounds are limited in the abstract."},{"rthcId":"RPEP-04632","title":"Serum VEGF Predicts Clinical Improvement Induced by Cerebrolysin Plus Donepezil in Patients With Advanced Alzheimer's Disease.","authors":"Alvarez, X Anton; Alvarez, Irene; Martinez, Antia; Romero, Iria; Benito, Concha; Suarez, Irene; Mourente, Silvia; Fantini, Manuel; Figueroa, Jesús; Aleixandre, Manuel; Linares, Carlos; Muresanu, Dafin; Winter, Stefan; Moessler, Herbert","year":2020,"journal":"The international journal of neuropsychopharmacology, 23(9), 581-586","doi":"10.1093/ijnp/pyaa046","pmid":"32640027","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04633","title":"Elevated Neurokinin-1 Receptor Expression in Uterine Products of Conception Is Associated With First Trimester Miscarriages.","authors":"Alwazzan, Ahmad; Mehboob, Riffat; Hassan, Amber; Perveen, Shahida; Sadaf; Gilani, Syed Amir; Ahmad, Fridoon Jawad; Tanvir, Imrana; Babar, Masroor Elahi; Tariq, Muhammad Akram; Ali, Gibran; Akram, Shehla Javed; Khan, Rizwan Ullah; Akram, Javed","year":2020,"journal":"Frontiers in physiology, 11, 554766","doi":"10.3389/fphys.2020.554766","pmid":"33391008","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04634","title":"Drug Delivery Strategies for Enhancing the Therapeutic Efficacy of Toxin-Derived Anti-Diabetic Peptides.","authors":"Amatya, Reeju; Park, Taehoon; Hwang, Seungmi; Yang, JaeWook; Lee, Yoonjin; Cheong, Heesun; Moon, Cheol; Kwak, Hyun Duck; Min, Kyoung Ah; Shin, Meong Cheol","year":2020,"journal":"Toxins, 12(5)","doi":"10.3390/toxins12050313","pmid":"32397648","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04635","title":"Role for Kisspeptin and Neurokinin B in Regulation of Luteinizing Hormone and Testosterone Secretion in the Fetal Sheep.","authors":"Amodei, Rebecka; Gribbin, Kyle; He, Wen; Lindgren, Isa; Corder, Keely R; Jonker, Sonnet S; Estill, Charles T; Coolen, Lique M; Lehman, Michael N; Whitler, William; Stormshak, Fred; Roselli, Charles E","year":2020,"journal":"Endocrinology, 161(4)","doi":"10.1210/endocr/bqaa013","pmid":"32005991","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04636","title":"Transcriptome analysis identifies immune-related genes and antimicrobial peptides in Siamese fighting fish (Betta splendens).","authors":"Amparyup, Piti; Charoensapsri, Walaiporn; Samaluka, Nusree; Chumtong, Parichat; Yocawibun, Patchari; Imjongjirak, Chanprapa","year":2020,"journal":"Fish & shellfish immunology, 99, 403-413","doi":"10.1016/j.fsi.2020.02.030","pmid":"32081810","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04637","title":"hDM2 protein-binding peptides screened from stapled α-helical peptide phage display libraries with different types of staple linkers.","authors":"Anananuchatkul, Teerapat; Tsutsumi, Hiroshi; Miki, Takayuki; Mihara, Hisakazu","year":2020,"journal":"Bioorganic & medicinal chemistry letters, 30(23), 127605","doi":"10.1016/j.bmcl.2020.127605","pmid":"33038548","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04638","title":"HLA-Arena: A Customizable Environment for the Structural Modeling and Analysis of Peptide-HLA Complexes for Cancer Immunotherapy.","authors":"Antunes, Dinler A; Abella, Jayvee R; Hall-Swan, Sarah; Devaurs, Didier; Conev, Anja; Moll, Mark; Lizée, Gregory; Kavraki, Lydia E","year":2020,"journal":"JCO clinical cancer informatics, 4, 623-636","doi":"10.1200/CCI.19.00123","pmid":"32667823","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04639","title":"Recombinant peptide derived from the venom the Phoneutria nigriventer spider relieves nociception by nerve deafferentation.","authors":"Antunes, Flavia Tasmin Techera; Angelo, Stephanie Gonçalves; Dallegrave, Eliane; Picada, Jaqueline Nascimento; Marroni, Norma Possa; Schemitt, Elizangela; Ferraz, Alice Gomes; Gomez, Marcus Vinicius; de Souza, Alessandra Hubner","year":2020,"journal":"Neuropeptides, 79, 101980","doi":"10.1016/j.npep.2019.101980","pmid":"31711615","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04640","title":"Calcitonin Gene-Related Peptide Antagonists for the Prevention of Migraine: Highlights From Pivotal Studies and the Clinical Relevance of This New Drug Class.","authors":"Arca, Karissa; Reynolds, Jenna; Sands, Kara A; Shiue, Harn J","year":2020,"journal":"The Annals of pharmacotherapy, 54(8), 795-803","doi":"10.1177/1060028020903417","pmid":"32019317","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Anti-CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab) reduced monthly migraine days in both chronic and episodic migraine with minimal clinically significant adverse events. Evidence also supports efficacy in refractory migraine patients despite optimal existing prophylaxis. This is the first target-specific migraine prophylaxis drug class — previous preventives were all repurposed from other indications and had poor side effect profiles.","whyItMatters":"Migraine affects hundreds of millions of people globally, yet prior preventive treatments were never designed for migraine and commonly cause side effects that lead patients to stop taking them. Anti-CGRP monoclonal antibodies represent a paradigm shift: the first drugs engineered specifically to target migraine biology, with efficacy demonstrated even in patients who failed other preventive treatments.","specificNumbers":"","methodology":"Structured literature review of PubMed (January 2009 to November 2019) using search terms for migraine, CGRP, erenumab, fremanezumab, and galcanezumab. Included human clinical trials and studies in English reporting pharmacology, efficacy, and adverse events. Excluded initial pharmacokinetic and preclinical studies.","limitations":"The literature search ended in November 2019, so longer-term real-world effectiveness and safety data accumulating after that point are not included. The review does not include eptinezumab (the fourth anti-CGRP mAb, approved in 2020). Specific numerical outcomes (effect sizes, responder rates) are not reported in the abstract. The high cost of CGRP antagonists is acknowledged as a barrier but not quantified."},{"rthcId":"RPEP-04641","title":"Effects of chronic intranasal oxytocin on behavior and cerebral glucose uptake in juvenile titi monkeys.","authors":"Arias Del Razo, Rocío; Berger, Trish; Conley, Alan J; Freeman, Sara M; Goetze, Leana R; Jacob, Suma; Lawrence, Rebecca H; Mendoza, Sally P; Rothwell, Emily S; Savidge, Logan E; Solomon, Marjorie; Weinstein, Tamara A R; Witczak, Lynea R; Bales, Karen L","year":2020,"journal":"Psychoneuroendocrinology, 113, 104494","doi":"10.1016/j.psyneuen.2019.104494","pmid":"31862614","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04642","title":"Murine cathelicidin: as a host defensive response against Leishmania major infection.","authors":"Asadi, Arash; Tavakoli Kareshk, Amir; Sharifi, Iraj; Firouzeh, Nima","year":2020,"journal":"Journal of parasitic diseases : official organ of the Indian Society for Parasitology, 44(3), 633-638","doi":"10.1007/s12639-020-01238-0","pmid":"32801517","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04643","title":"Increased level of cathelicidin (LL-37) in vitiligo: Possible pathway independent from vitamin D receptor gene polymorphism.","authors":"Atazadeh, Fatemeh; Fazeli, Zahra; Vahidnezhad, Hassan; Namazi, Nastaran; Younespour, Shima; Youssefian, Leila; Abdollahimajd, Fahimeh; Uitto, Jouni","year":2020,"journal":"Experimental dermatology, 29(12), 1176-1185","doi":"10.1111/exd.14200","pmid":"32997837","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04644","title":"Microbial Fermentation of Industrial Rice-Starch Byproduct as Valuable Source of Peptide Fractions with Health-Related Activity.","authors":"Babini, Elena; Taneyo-Saa, Danielle Laure; Tassoni, Annalisa; Ferri, Maura; Kraft, Axel; Grän-Heedfeld, Jürgen; Bretz, Karlheinz; Roda, Aldo; Michelini, Elisa; Calabretta, Maria Maddalena; Guillon, Fabien; Tagliazucchi, Davide; Martini, Serena; Nissen, Lorenzo; Gianotti, Andrea","year":2020,"journal":"Microorganisms, 8(7)","doi":"10.3390/microorganisms8070986","pmid":"32630107","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04645","title":"N-locking stabilization of covalent helical peptides: Application to Bfl-1 antagonists.","authors":"Baggio, Carlo; Udompholkul, Parima; Gambini, Luca; Jossart, Jennifer; Salem, Ahmed F; Håkansson, Maria; Perry, J Jefferson P; Pellecchia, Maurizio","year":2020,"journal":"Chemical biology & drug design, 95(4), 412-426","doi":"10.1111/cbdd.13661","pmid":"31898401","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04646","title":"Endogenous opioid peptides in the descending pain modulatory circuit.","authors":"Bagley, Elena E; Ingram, Susan L","year":2020,"journal":"Neuropharmacology, 173, 108131","doi":"10.1016/j.neuropharm.2020.108131","pmid":"32422213","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04647","title":"Multiple functions of thymosin β4 in the pearl oyster Pinctada fucata suggest its multiple potential roles in artificial pearl culture.","authors":"Bai, Lirong; He, Wenyao; Fan, Sigang; Liu, Baosuo; Zhou, Tong; Zhang, Dongling; Zhang, Dianchang; Yu, Dahui","year":2020,"journal":"Fish & shellfish immunology, 103, 23-31","doi":"10.1016/j.fsi.2020.04.040","pmid":"32348884","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04648","title":"Recombinant Peptide Production Platform Coupled with Site-Specific Albumin Conjugation Enables a Convenient Production of Long-Acting Therapeutic Peptide.","authors":"Bak, Mijeong; Park, Junyong; Min, Kiyoon; Cho, Jinhwan; Seong, Jihyoun; Hahn, Young S; Tae, Giyoong; Kwon, Inchan","year":2020,"journal":"Pharmaceutics, 12(4)","doi":"10.3390/pharmaceutics12040364","pmid":"32316169","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The researchers successfully produced recombinant GLP-1 with a non-natural amino acid (p-azido-L-phenylalanine) incorporated at three specific positions (V16, Y19, and F28), then conjugated human serum albumin (HSA) at each site using click chemistry (strain-promoted azide-alkyne cycloaddition).\n\nAll three HSA-conjugated GLP-1 variants achieved comparable extended serum half-lives in vivo. However, their biological activities differed significantly: the variants showed different in vitro receptor activation and different glucose-lowering effects in vivo, demonstrating that the specific site of albumin attachment critically affects therapeutic function even when half-life extension is equivalent.","whyItMatters":"Peptide drugs are one of the fastest-growing segments of the pharmaceutical industry, but their short half-lives mean patients often need daily or even more frequent injections. This platform offers a generalizable solution: produce the peptide in bacteria (overcoming size limits of chemical synthesis) and attach albumin at the optimal site (extending duration without sacrificing activity). If the approach scales, it could accelerate the development of many long-acting peptide therapies beyond just GLP-1.","specificNumbers":"","methodology":"The team used genetic code expansion to incorporate a clickable non-natural amino acid (AzF) at three specific positions in a GLP-1 variant produced in bacteria. They then conjugated HSA to each variant using strain-promoted azide-alkyne cycloaddition (a type of click chemistry that works under mild conditions). The conjugates were tested for in vitro biological activity (receptor activation assays) and in vivo performance including serum half-life and glucose-lowering effects in animal models.","limitations":"The study used GLP-1 as a single model peptide, so the platform's effectiveness for other therapeutic peptides remains to be demonstrated. Only three conjugation sites were tested. The in vivo studies were conducted in animal models, and translation to human pharmacokinetics is uncertain. The recombinant production yield and scalability for manufacturing were not fully characterized. Long-term stability and immunogenicity of the conjugates were not assessed."},{"rthcId":"RPEP-04649","title":"GHRH Antagonists Protect Against Hydrogen Peroxide-Induced Breakdown of Brain Microvascular Endothelium Integrity.","authors":"Barabutis, Nektarios; Akhter, Mohammad S; Uddin, Mohammad A; Kubra, Khadeja-Tul; Schally, Andrew V","year":2020,"journal":"Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme, 52(5), 336-339","doi":"10.1055/a-1149-9347","pmid":"32403147","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04650","title":"Blocking substance P signaling reduces musculotendinous and dermal fibrosis and sensorimotor declines in a rat model of overuse injury.","authors":"Barbe, M F; Hilliard, B A; Fisher, P W; White, A R; Delany, S P; Iannarone, V J; Harris, M Y; Amin, M; Cruz, G E; Popoff, S N","year":2020,"journal":"Connective tissue research, 61(6), 604-619","doi":"10.1080/03008207.2019.1653289","pmid":"31443618","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"NK1R antagonist treatment (L-732,138) in rats performing a high repetition high force (HRHF) task produced multiple beneficial effects compared to untreated HRHF rats:\n- Improved grip strength (reversed task-induced decline)\n- Reduced mechanical sensitivity and temperature aversion (pain measures)\n- Reduced flexor digitorum epitendon thickening\n- Decreased HRHF-induced increases of fibrotic markers TGFβ1, CCN2/CTGF, and collagen type 1 in flexor digitorum muscles\n- Reduced task-induced collagen deposition in forepaw upper dermis\n\nThese findings demonstrate that Substance P-NK1R signaling drives fibrogenic responses and associated pain in overuse injuries across multiple tissue types (tendon, muscle, skin).","whyItMatters":"Repetitive strain injuries (carpal tunnel syndrome, tendinitis, trigger finger) affect millions of workers and athletes, and current treatments often provide only temporary relief. This research identifies Substance P as a treatable cause of the tissue scarring that drives chronic pain and disability in these conditions, opening the door to NK1R antagonist therapy as a disease-modifying treatment rather than just symptom management.","specificNumbers":"","methodology":"Young adult Sprague-Dawley rats learned to pull at high force levels over 5 weeks, then performed a high repetition high force (HRHF) task for 3 weeks (2 hours/day, 3 days/week). Groups included untreated HRHF, NK1RA-treated HRHF (L-732,138 IP in weeks 2-3), and controls with vehicle or NK1RA. Outcomes assessed: grip strength, mechanical sensitivity, temperature aversion, epitendon thickness, muscle fibrotic markers (TGFβ1, CCN2/CTGF, collagen type 1), and dermal collagen deposition.","limitations":"The study was conducted in young adult rats performing a controlled task, which may not fully replicate the complexity and chronicity of human repetitive strain injuries. NK1RA treatment was given for only 2 weeks during an 8-week protocol, so long-term treatment effects are unknown. The study did not assess whether fibrotic changes reversed after longer treatment or whether benefits persisted after stopping the drug."},{"rthcId":"RPEP-04651","title":"A nucleus-directed bombesin derivative for targeted delivery of metallodrugs to cancer cells.","authors":"Barrabés, Sílvia; Ng-Choi, Iteng; Martínez, María Ángeles; Manzano, Blanca R; Jalón, Félix A; Espino, Gustavo; Feliu, Lidia; Planas, Marta; de Llorens, Rafael; Massaguer, Anna","year":2020,"journal":"Journal of inorganic biochemistry, 212, 111214","doi":"10.1016/j.jinorgbio.2020.111214","pmid":"32919249","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04652","title":"Screening and identification of BP100 peptide conjugates active against Xylella fastidiosa using a viability-qPCR method.","authors":"Baró, Aina; Badosa, Esther; Montesinos, Laura; Feliu, Lidia; Planas, Marta; Montesinos, Emilio; Bonaterra, Anna","year":2020,"journal":"BMC microbiology, 20(1), 229","doi":"10.1186/s12866-020-01915-3","pmid":"32727358","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04653","title":"DNA methylation of ghrelin and leptin receptors in underweight and recovered patients with anorexia nervosa.","authors":"Batury, Victoria-Luise; Walton, Esther; Tam, Friederike; Wronski, Marie-Louis; Buchholz, Vanessa; Frieling, Helge; Ehrlich, Stefan","year":2020,"journal":"Journal of psychiatric research, 131, 271-278","doi":"10.1016/j.jpsychires.2020.08.026","pmid":"33091847","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04654","title":"Serum vitamin D concentration is associated with antimicrobial peptide level in periodontal diseases.","authors":"Bayirli, Batuhan A; Öztürk, Ayla; Avci, Bahattin","year":2020,"journal":"Archives of oral biology, 117, 104827","doi":"10.1016/j.archoralbio.2020.104827","pmid":"32673820","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04655","title":"F-Actin is associated with a worsening qSOFA score and intensive care unit admission in emergency department patients at risk for sepsis.","authors":"Belsky, Justin B; Filbin, Michael R; Rivers, Emanuel P; Bobbitt, Kevin R; Jaehne, Anja K; Wisnik, Christopher A; Maciejewski, Kaitlin R; Li, Fangyong; Morris, Daniel C","year":2020,"journal":"Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals, 25(5), 391-396","doi":"10.1080/1354750X.2020.1771419","pmid":"32421363","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04656","title":"DNA damage and growth hormone hypersecretion in pituitary somatotroph adenomas.","authors":"Ben-Shlomo, Anat; Deng, Nan; Ding, Evelyn; Yamamoto, Masaaki; Mamelak, Adam; Chesnokova, Vera; Labadzhyan, Artak; Melmed, Shlomo","year":2020,"journal":"The Journal of clinical investigation, 130(11), 5738-5755","doi":"10.1172/JCI138540","pmid":"32673291","tags":["growth-hormone"],"studyType":"lab-study","evidenceStrength":"moderate","keyFinding":"Whole-exome sequencing of 159 surgically removed pituitary adenomas revealed that somatic copy number alterations (SCNAs) — not point mutations — are the hallmark of hormone-secreting pituitary tumors. In growth hormone-secreting tumors specifically, cAMP signaling and DNA damage repair pathways were both affected.\n\nThe key discovery: cAMP, the same signaling molecule that drives GH secretion and cell growth, simultaneously causes DNA damage. This creates a vicious cycle where hormone overproduction and genomic instability are mechanistically linked. Octreotide, a somatostatin analog used to treat acromegaly, inhibited cAMP and reversed the DNA damage — suggesting treatment may address the tumor biology, not just the hormone excess.","whyItMatters":"Pituitary adenomas are the most common intracranial tumors, yet scientists have struggled to explain what drives their growth since they rarely carry the classic cancer mutations. This study provides a breakthrough: the same pathway that makes these tumors overproduce growth hormone also damages their DNA, creating genomic instability. This links hormone overproduction to tumor biology for the first time and suggests that somatostatin analog treatment (octreotide) may do more than just control GH levels — it may address the underlying genomic damage.","specificNumbers":"159 pituitary adenomas sequenced · SCNAs > mutations as driver · cAMP pathway and Fanconi anemia repair pathway affected · Octreotide reversed DNA damage · Mouse primary pituitary cultures + in vivo validation","methodology":"Combined whole-exome sequencing of 159 human pituitary adenomas with functional experiments in mouse pituitary cell cultures and in vivo mouse models. DNA damage was measured using H2AX phosphorylation and comet assays. cAMP was stimulated with forskolin or GHRH analog, and inhibited with octreotide.","limitations":"The functional experiments linking cAMP to DNA damage were performed in mouse cells and mice, not directly in human tumors. The 159-adenoma sequencing cohort provides strong genomic data, but the mechanistic conclusions require further validation in human tissue. The study focused on somatotroph adenomas and may not generalize to other pituitary tumor types."},{"rthcId":"RPEP-04657","title":"Chicken Egg Proteins and Derived Peptides with Antioxidant Properties.","authors":"Benedé, Sara; Molina, Elena","year":2020,"journal":"Foods (Basel, Switzerland), 9(6)","doi":"10.3390/foods9060735","pmid":"32503187","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04658","title":"MMAE Delivery Using the Bicycle Toxin Conjugate BT5528.","authors":"Bennett, Gavin; Brown, Amy; Mudd, Gemma; Huxley, Philip; Van Rietschoten, Katerine; Pavan, Silvia; Chen, Liuhong; Watcham, Sophie; Lahdenranta, Johanna; Keen, Nicholas","year":2020,"journal":"Molecular cancer therapeutics, 19(7), 1385-1394","doi":"10.1158/1535-7163.MCT-19-1092","pmid":"32398269","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04659","title":"Cystatin C as a biomarker of chronic kidney disease: latest developments.","authors":"Benoit, Stefanie W; Ciccia, Eileen A; Devarajan, Prasad","year":2020,"journal":"Expert review of molecular diagnostics, 20(10), 1019-1026","doi":"10.1080/14737159.2020.1768849","pmid":"32450046","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04660","title":"Safety of Rimegepant, an Oral CGRP Receptor Antagonist, Plus CGRP Monoclonal Antibodies for Migraine.","authors":"Berman, Gary; Croop, Robert; Kudrow, David; Halverson, Philip; Lovegren, Meghan; Thiry, Alexandra C; Conway, Charles M; Coric, Vladimir; Lipton, Richard B","year":2020,"journal":"Headache, 60(8), 1734-1742","doi":"10.1111/head.13930","pmid":"32799325","tags":[],"studyType":"open-label safety substudy","evidenceStrength":"low","keyFinding":"Combining the oral CGRP receptor antagonist rimegepant (75 mg as needed) with injectable CGRP monoclonal antibodies (erenumab, fremanezumab, or galcanezumab) for migraine was well tolerated in 13 patients over approximately 10 weeks. A total of 224 rimegepant doses were taken. Five patients (38%) reported mild adverse events, most commonly nasopharyngitis. Three patients had mild-to-moderate events considered potentially treatment-related. No serious adverse events, no treatment discontinuations, and no liver enzyme elevations occurred. This provides the first systematic safety data for using two different CGRP-targeting therapies simultaneously.","whyItMatters":"Many migraine patients use a CGRP antibody injection monthly for prevention but still need acute treatment when breakthrough attacks occur. Using a gepant (like rimegepant) for these attacks means both the preventive and acute treatments block the same CGRP pathway, raising theoretical safety concerns about \"double CGRP blockade.\" This study provides reassurance that the combination appears safe — an important practical finding because it validates a treatment approach clinicians are already using in practice.","specificNumbers":"n=13 · 224 total rimegepant doses · Mean 7.8 doses per 4 weeks · 9.6 weeks mean treatment · 38% had ≥1 AE · 15% nasopharyngitis · 0 serious AEs · 0 discontinuations · 0 liver enzyme elevations >3× ULN","methodology":"This was a substudy nested within a larger multicenter, open-label, long-term rimegepant safety study. Thirteen patients with 2-8 monthly migraine attacks who were already on stable CGRP mAb therapy (erenumab n=7, fremanezumab n=4, galcanezumab n=2) took rimegepant 75 mg as needed (up to once daily) for acute treatment over 12 weeks. Safety was assessed through adverse event monitoring and liver enzyme testing.","limitations":"The sample size of 13 is very small — too small to detect rare safety signals. The study is open-label with no control group. The 12-week duration may not capture long-term safety concerns. The study cannot assess whether dual CGRP blockade reduces efficacy of either drug. The highly selected patient population (stable on CGRP mAb, moderate attack frequency) may not represent all patients who would use this combination in practice."},{"rthcId":"RPEP-04661","title":"Behavioral effects of multiple-dose oxytocin treatment in autism: a randomized, placebo-controlled trial with long-term follow-up.","authors":"Bernaerts, Sylvie; Boets, Bart; Bosmans, Guy; Steyaert, Jean; Alaerts, Kaat","year":2020,"journal":"Molecular autism, 11(1), 6","doi":"10.1186/s13229-020-0313-1","pmid":"31969977","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Primary outcome: No significant treatment-specific improvement in social responsiveness (Social Responsiveness Scale). Both oxytocin and placebo groups showed improvement, with no significant between-group difference (self-report p=0.37, informant-rated p=0.19).\n\nSecondary outcomes with significant treatment-specific effects:\n- Repetitive Behavior Scale: Reduced self-reported repetitive behaviors in oxytocin group (p=0.04), persisting up to 1 month and even 1 year post-treatment\n- State Adult Attachment Measure: Reduced feelings of avoidance toward others (p=0.03), lasting up to 1 year\n- Profile of Mood States: Higher reports of vigor (energy, activity, liveliness) in oxytocin group (p=0.03)\n\nThese secondary benefits persisted well beyond the 4-week treatment period, suggesting potential long-lasting neuroplastic effects.","whyItMatters":"This is one of the first oxytocin trials in autism to include long-term follow-up (up to 1 year). While the failure to improve core social symptoms is disappointing, the discovery of lasting effects on repetitive behaviors and avoidance is intriguing because: (1) repetitive behaviors are a core autism feature that significantly impacts quality of life, (2) effects persisting 1 year after only 4 weeks of treatment suggest oxytocin may trigger lasting neural changes rather than just temporary chemical effects, and (3) this shifts the conversation about which autism features oxytocin might actually help.","specificNumbers":"","methodology":"This was a double-blind, randomized, placebo-controlled, parallel-group pilot trial (Eudract 2014-000586-45). Forty adult men with ASD received either intranasal oxytocin (24 IU once daily in the morning) or placebo for 4 weeks. Assessments were conducted at baseline, immediately post-treatment (~24 hours after last dose), 4 weeks post-treatment, and 1 year post-treatment. Outcomes included self-report and informant-based questionnaires measuring social responsiveness, repetitive behaviors, attachment style, and mood states.","limitations":"This is a small pilot study (n=40) with multiple secondary outcome comparisons, increasing the risk of false positive findings. The p-values for significant secondary outcomes (0.03-0.04) would not survive correction for multiple comparisons. Only adult men were included, limiting generalizability to women and children with autism. Self-report measures are inherently subjective, particularly for individuals with ASD who may have difficulty with self-assessment. The strong placebo response in social responsiveness measures is notable and complicates interpretation. The 24 IU dose and once-daily regimen may not be optimal."},{"rthcId":"RPEP-04662","title":"Milk Peptides Survive In Vivo Gastrointestinal Digestion and Are Excreted in the Stool of Infants.","authors":"Beverly, Robert L; Huston, Robert K; Markell, Andi M; McCulley, Elizabeth A; Martin, Rachel L; Dallas, David C","year":2020,"journal":"The Journal of nutrition, 150(4), 712-721","doi":"10.1093/jn/nxz326","pmid":"31883006","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04663","title":"Release of functional dexamethasone by intracellular enzymes: A modular peptide-based strategy for ocular drug delivery.","authors":"Bhattacharya, Madhushree; Sadeghi, Amir; Sarkhel, Sanjay; Hagström, Marja; Bahrpeyma, Sina; Toropainen, Elisa; Auriola, Seppo; Urtti, Arto","year":2020,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 327, 584-594","doi":"10.1016/j.jconrel.2020.09.005","pmid":"32911015","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04664","title":"PASylated Thymosin α1: A Long-Acting Immunostimulatory Peptide for Applications in Oncology and Virology.","authors":"Binder, Uli; Skerra, Arne","year":2020,"journal":"International journal of molecular sciences, 22(1)","doi":"10.3390/ijms22010124","pmid":"33374407","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04665","title":"Thymosin β4: A Multi-Faceted Tissue Repair Stimulating Protein in Heart Injury.","authors":"Bjørklund, Geir; Dadar, Maryam; Aaseth, Jan; Chirumbolo, Salvatore","year":2020,"journal":"Current medicinal chemistry, 27(37), 6294-6305","doi":"10.2174/0929867326666190716125456","pmid":"31333080","tags":["healing-and-recovery-peptides","cardiovascular-peptides"],"studyType":"narrative-review","evidenceStrength":"low","keyFinding":"This review consolidates evidence that thymosin beta-4 (Tβ4) promotes cardiac tissue repair through multiple mechanisms. Tβ4 activates resident epicardial progenitor cells — stem-like cells sitting on the heart's surface — and modulates inflammatory injury, both of which promote the survival of cardiomyocytes (heart muscle cells) after myocardial infarction.\n\nBeyond the heart, the review notes Tβ4's roles in tissue repair after stroke, in peripheral and central nervous system remodeling, and in skeletal muscle recovery. It may work synergistically with other repair-promoting factors including melatonin and C-fiber-derived peptides.","whyItMatters":"Heart attacks destroy heart muscle that the body struggles to replace. Tβ4 is one of the few peptides shown to activate the heart's own dormant progenitor cells and reduce inflammatory damage after cardiac injury. If these effects translate to clinical use, Tβ4 could help the heart heal itself rather than just forming scar tissue — a fundamentally different approach from current post-heart-attack care.","specificNumbers":"Review paper · No original numerical data · Covers cardiac, neural, and skeletal muscle repair · Tβ4 activates epicardial progenitor cells · Promotes cardiomyocyte survival","methodology":"Narrative review synthesizing published literature on thymosin beta-4's tissue repair properties, with a focus on cardiac applications. Covers preclinical and mechanistic studies across multiple organ systems.","limitations":"Narrative review without systematic search methodology, so subject to selection bias. Most evidence discussed is preclinical. The review does not quantify effect sizes or critically appraise the quality of individual studies. Tβ4's connection to tumorigenesis is acknowledged but not deeply explored as a safety concern."},{"rthcId":"RPEP-04666","title":"Enhanced Cellular Transduction of Nanoparticles Resistant to Rapidly Forming Plasma Protein Coronas.","authors":"Blokpoel Ferreras, Lia A; Scott, Daniel; Vazquez Reina, Saul; Roach, Paul; Torres, Teobaldo E; Goya, Gerardo F; Shakesheff, Kevin M; Dixon, James E","year":2020,"journal":"Advanced biosystems, 4(10), e2000162","doi":"10.1002/adbi.202000162","pmid":"32924327","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04667","title":"The Network of Colonic Host Defense Peptides as an Innate Immune Defense Against Enteropathogenic Bacteria.","authors":"Blyth, Graham A D; Connors, Liam; Fodor, Cristina; Cobo, Eduardo R","year":2020,"journal":"Frontiers in immunology, 11, 965","doi":"10.3389/fimmu.2020.00965","pmid":"32508838","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04668","title":"Pro-atrial natriuretic peptide and pro-adrenomedullin before cardiac surgery in children. Can we predict the future?","authors":"Bobillo-Perez, Sara; Girona-Alarcon, Monica; Corniero, Patricia; Sole-Ribalta, Anna; Balaguer, Monica; Esteban, Elisabeth; Valls, Anna; Jordan, Iolanda; Cambra, Francisco Jose","year":2020,"journal":"PloS one, 15(7), e0236377","doi":"10.1371/journal.pone.0236377","pmid":"32702064","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04669","title":"Endogenous Opiates and Behavior: 2018.","authors":"Bodnar, Richard J","year":2020,"journal":"Peptides, 132, 170348","doi":"10.1016/j.peptides.2020.170348","pmid":"32574695","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04670","title":"Endogenous opiates and behavior: 2017.","authors":"Bodnar, Richard J","year":2020,"journal":"Peptides, 124, 170223","doi":"10.1016/j.peptides.2019.170223","pmid":"31805297","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04671","title":"Molecular Motions and Interactions in Aqueous Solutions of Thymosin-β4 , Stabilin CTD and Their 1 : 1 Complex, Studied by 1 H-NMR Spectroscopy.","authors":"Bokor, M; Tantos, Á; Mészáros, A; Jenei, B; Haminda, R; Tompa, P; Tompa, K","year":2020,"journal":"Chemphyschem : a European journal of chemical physics and physical chemistry, 21(13), 1420-1428","doi":"10.1002/cphc.202000264","pmid":"32469123","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04672","title":"Ternary Cu(II) Complex with GHK Peptide and Cis-Urocanic Acid as a Potential Physiologically Functional Copper Chelate.","authors":"Bossak-Ahmad, Karolina; Wiśniewska, Marta D; Bal, Wojciech; Drew, Simon C; Frączyk, Tomasz","year":2020,"journal":"International journal of molecular sciences, 21(17)","doi":"10.3390/ijms21176190","pmid":"32867146","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The study demonstrates that cis-urocanic acid, previously not known as a significant copper binder, can coordinate Cu(II) ions. More importantly, GHK and cis-urocanic acid can both bind to the same Cu(II) ion simultaneously, forming a ternary complex [GHK][Cu(II)][cis-urocanic acid].\n\nBased on the natural concentrations of these three molecules in human tissues (particularly skin and plasma) and the binding affinities measured, the authors conclude that this ternary complex likely exists in the body and may be partly responsible for the biological effects previously attributed to GHK or urocanic acid individually.","whyItMatters":"GHK-Cu is widely used in skincare for its wound healing and anti-aging properties, but its exact mechanism isn't fully understood. If GHK-Cu naturally forms a ternary complex with urocanic acid in skin, this could change how we understand the peptide's biology — the active species in the body may not be simple GHK-Cu but a more complex molecular partnership.","specificNumbers":"","methodology":"Biophysical chemistry study using spectroscopic techniques. Copper binding was characterized using electron spin resonance (ESR) spectroscopy and circular dichroism (CD). Binding affinities were measured and compared to known physiological concentrations of GHK, copper, and urocanic acid in human tissues.","limitations":"This is a chemistry study measuring binding interactions, not a biological study testing cellular or physiological effects. The authors infer physiological relevance from concentrations and affinities but did not directly demonstrate the ternary complex forming in living tissue. The biological consequences of the ternary complex versus simple GHK-Cu were not tested."},{"rthcId":"RPEP-04673","title":"Discovery of Membrane-Permeating Cyclic Peptides via mRNA Display.","authors":"Bowen, John; Schloop, Allison E; Reeves, Gregory T; Menegatti, Stefano; Rao, Balaji M","year":2020,"journal":"Bioconjugate chemistry, 31(10), 2325-2338","doi":"10.1021/acs.bioconjchem.0c00413","pmid":"32786364","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Researchers used mRNA display — a technique that screens trillions of peptide variants simultaneously — to discover cyclic peptides capable of penetrating biological membranes. The top hit, cyclo[Glut-MRKRHASRRE-K*], successfully penetrated both fruit fly embryos and mammalian cells (human embryonic stem cells and mouse fibroblasts). This is notable because no previously known peptide could cross both cytoplasmic membranes and the tough outer embryonic membrane. The cyclic version significantly outperformed its linear (non-cyclized) counterpart.","whyItMatters":"One of the biggest challenges in drug delivery is getting therapeutic molecules inside cells. Cell-penetrating peptides are promising delivery vehicles, but most have limited ability to cross different types of membranes. This study introduces a high-throughput method to discover cyclic peptides with unusually broad membrane-penetrating ability — which could be used to deliver drugs, gene therapies, or research tools into cells that were previously difficult to access.","specificNumbers":"","methodology":"The researchers constructed large libraries of cyclic peptides using mRNA display, a technique where each peptide is physically linked to its own genetic code, allowing rapid identification of hits. They screened these libraries against fruit fly embryos at different developmental stages to select peptides that could penetrate tough embryonic membranes. Top candidates were then tested against mammalian cells. Permeation was measured using confocal microscopy (visual confirmation) and flow cytometry (quantitative measurement of how much peptide entered cells).","limitations":"This is an in vitro proof-of-concept study. The peptides were tested in cell lines and embryos, not in living organisms. Whether they can deliver actual drug cargo — not just themselves — across membranes hasn't been demonstrated. The fruit fly embryo screen may select for properties that don't perfectly translate to all mammalian cell types. Toxicity at therapeutic doses in vivo is unknown."},{"rthcId":"RPEP-04674","title":"1,25(OH)D vitamin D promotes NOS2 expression in response to bacterial and viral PAMPs in primary bovine salivary gland fibroblasts.","authors":"Boylan, Malena; O'Brien, Megan B; Beynon, Charlotte; Meade, Kieran G","year":2020,"journal":"Veterinary research communications, 44(2), 83-88","doi":"10.1007/s11259-020-09775-y","pmid":"32440968","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04675","title":"Secretin effects on gastric functions, hormones and symptoms in functional dyspepsia and health: randomized crossover trial.","authors":"Brandler, Justin; Miller, Laurence J; Wang, Xiao Jing; Burton, Duane; Busciglio, Irene; Arndt, Kayla; Harmsen, William S; Camilleri, Michael","year":2020,"journal":"American journal of physiology. Gastrointestinal and liver physiology, 318(4), G635-G645","doi":"10.1152/ajpgi.00371.2019","pmid":"32036693","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04676","title":"Antiviral Activities of Human Host Defense Peptides.","authors":"Brice, David C; Diamond, Gill","year":2020,"journal":"Current medicinal chemistry, 27(9), 1420-1443","doi":"10.2174/0929867326666190805151654","pmid":"31385762","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04677","title":"Phenylalanine Stereoisomers of CJ-15,208 and [d-Trp]CJ-15,208 Exhibit Distinctly Different Opioid Activity Profiles.","authors":"Brice-Tutt, Ariana C; Senadheera, Sanjeewa N; Ganno, Michelle L; Eans, Shainnel O; Khaliq, Tanvir; Murray, Thomas F; McLaughlin, Jay P; Aldrich, Jane V","year":2020,"journal":"Molecules (Basel, Switzerland), 25(17)","doi":"10.3390/molecules25173999","pmid":"32887303","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04678","title":"Monoclonal antibodies against calcitonin gene-related peptide in chronic migraine: an adjusted indirect treatment comparison.","authors":"Briceño-Casado, María Del Pilar; Gil-Sierra, Manuel David; Fénix-Caballero, Silvia","year":2020,"journal":"Farmacia hospitalaria : organo oficial de expresion cientifica de la Sociedad Espanola de Farmacia Hospitalaria, 44(5), 212-217","doi":"10.7399/fh.11419","pmid":"32853126","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"From 30 identified randomized clinical trials, three studies met inclusion criteria for indirect treatment comparison (one each for erenumab, fremanezumab, and eptinezumab). Using Bucher's method for adjusted indirect comparison:\n\n- No statistically significant differences in the proportion of patients achieving ≥50% reduction in monthly migraine days between any of the three drugs\n- Most of the 95% confidence intervals fell within the calculated equivalence delta margin (Δ = 9.5%)\n- No relevant safety differences were found among the three drugs\n- The drugs were assessed as probable clinical equivalents in terms of efficacy and safety for chronic migraine prevention","whyItMatters":"When multiple drugs in the same class are available, clinicians and formulary committees need to know whether they can be considered interchangeable. This study provides evidence that erenumab, fremanezumab, and eptinezumab are therapeutically equivalent for chronic migraine, meaning drug selection can be based on practical considerations: erenumab and fremanezumab are monthly subcutaneous injections, eptinezumab is a quarterly intravenous infusion. Cost, insurance coverage, and patient preference become the deciding factors rather than efficacy.","specificNumbers":"","methodology":"Systematic literature search of PubMed through December 2019 for phase II/III randomized clinical trials of CGRP-pathway monoclonal antibodies. Inclusion criteria required similar populations, follow-up lengths, and comparators (placebo). The primary efficacy endpoint was ≥50% reduction in migraine days per month. Chronic migraine was defined as ≥15 headache days/month with ≥8 migraine days (≥4 hours each). Adjusted indirect comparison used Bucher's method. Equivalence was assessed using a positioning guide with delta value calculated as half the absolute risk reduction from meta-analysis.","limitations":"Indirect treatment comparisons are less reliable than head-to-head randomized trials. Only 3 of 30 identified trials met the strict inclusion criteria, limiting the analysis. Galcanezumab was identified in the search but no suitable trial met criteria for inclusion. The analysis was limited to one efficacy endpoint (≥50% migraine day reduction) and didn't assess other outcomes like total migraine day reduction or patient-reported outcomes. The search was conducted in 2019 and doesn't include more recent evidence."},{"rthcId":"RPEP-04679","title":"Integrating oral semaglutide into clinical practice in primary care: for whom, when, and how?","authors":"Brunton, Stephen A; Mosenzon, Ofri; Wright, Eugene E","year":2020,"journal":"Postgraduate medicine, 132(sup2), 48-60","doi":"10.1080/00325481.2020.1798162","pmid":"32815453","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The article identifies five patient populations most likely to benefit from oral semaglutide: (1) patients with inadequate glycemic control on one or more oral medications; (2) patients who would benefit from weight loss; (3) patients at risk of hypoglycemia; (4) patients who would be candidates for injectable GLP-1RAs but prefer oral therapy; and (5) patients on basal insulin needing treatment intensification.\n\nCritical administration requirements include: swallowing the tablet whole with no more than 4 oz (120 mL) of plain water on an empty stomach upon waking, then waiting at least 30 minutes before eating, drinking, or taking other oral medications. Food and excess liquid significantly reduce absorption. Gradual dose escalation is recommended to minimize gastrointestinal side effects.","whyItMatters":"Many patients with type 2 diabetes are reluctant to start injectable GLP-1 receptor agonists despite their proven benefits for blood sugar control, weight loss, and cardiovascular protection. Oral semaglutide removed the injection barrier, but its unique dosing requirements — empty stomach, limited water, 30-minute fast — represent a new set of challenges. Practical guidance on patient selection and counseling is essential for primary care providers to use this medication effectively and ensure patients adhere to the administration protocol.","specificNumbers":"","methodology":"This is a clinical guidance/review article synthesizing evidence from the PIONEER trial program (oral semaglutide's registration studies) to provide practical recommendations for primary care clinicians. It is not a primary research study.","limitations":"As a clinical guidance article rather than an original study, it does not present new data. The recommendations are based primarily on the PIONEER trial program, which studied specific patient populations under controlled conditions — real-world adherence to the strict dosing requirements may be lower. The article does not cover oral semaglutide's use for weight management (which was approved later at a higher dose). Guidance reflects the 2020 evidence base and may not incorporate more recent clinical experience."},{"rthcId":"RPEP-04680","title":"Aromatic Cytokinin Arabinosides Promote PAMP-like Responses and Positively Regulate Leaf Longevity.","authors":"Bryksová, Magdaléna; Dabravolski, Siarhei; Kučerová, Zuzana; Zavadil Kokáš, Filip; Špundová, Martina; Plíhalová, Lucie; Takáč, Tomáš; Grúz, Jiří; Hudeček, Martin; Hloušková, Veronika; Koprna, Radoslav; Novák, Ondřej; Strnad, Miroslav; Plíhal, Ondřej; Doležal, Karel","year":2020,"journal":"ACS chemical biology, 15(7), 1949-1963","doi":"10.1021/acschembio.0c00306","pmid":"32520524","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04681","title":"Opioid Peptides and Their Receptors in Chickens: Structure, Functionality, and Tissue Distribution.","authors":"Bu, Guixian; Cui, Lin; Lv, Can; Lin, Dongliang; Huang, Long; Li, Zhengyang; Li, Juan; Zeng, Xianyin; Wang, Yajun","year":2020,"journal":"Peptides, 128, 170307","doi":"10.1016/j.peptides.2020.170307","pmid":"32217145","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04682","title":"Antimicrobial Peptides and Cell-Penetrating Peptides for Treating Intracellular Bacterial Infections.","authors":"Buccini, Danieli F; Cardoso, Marlon H; Franco, Octavio L","year":2020,"journal":"Frontiers in cellular and infection microbiology, 10, 612931","doi":"10.3389/fcimb.2020.612931","pmid":"33614528","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04683","title":"CGRP antagonists for decreasing migraine frequency: New options, long overdue.","authors":"Bucklan, Julia; Ahmed, Zubair","year":2020,"journal":"Cleveland Clinic journal of medicine, 87(4), 211-218","doi":"10.3949/ccjm.87a.19048","pmid":"32238376","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Four monoclonal antibodies targeting the CGRP pathway have been approved for migraine prevention:\n\n- Erenumab: targets the CGRP receptor\n- Galcanezumab: targets the CGRP peptide\n- Fremanezumab: targets the CGRP peptide\n- Eptinezumab: targets the CGRP peptide\n\nThese are the first drugs specifically developed for migraine prevention, replacing reliance on repurposed medications from other therapeutic areas.","whyItMatters":"Before anti-CGRP antibodies, migraine prevention was limited to drugs borrowed from other fields — beta-blockers, antidepressants, and antiepileptics — which often had significant side effects and modest efficacy. The development of drugs that specifically target the CGRP peptide pathway represents the first mechanism-based approach to migraine prevention, offering improved tolerability and a treatment rationale grounded in migraine biology.","specificNumbers":"","methodology":"This is a clinical review article published in the Cleveland Clinic Journal of Medicine summarizing the pharmacology, mechanism, and clinical role of anti-CGRP monoclonal antibodies for migraine prevention.","limitations":"The abstract provides only a brief overview without specific efficacy data, response rates, or side effect profiles. As a review published in 2020, it does not cover subsequent developments like gepants, newer delivery methods, or long-term real-world effectiveness data. The cost and access barriers to monoclonal antibody therapies are not discussed."},{"rthcId":"RPEP-04684","title":"Plasma Cathelicidin is Independently Associated with Reduced Lung Function in COPD: Analysis of the Subpopulations and Intermediate Outcome Measures in COPD Study Cohort.","authors":"Burkes, Robert M; Ceppe, Agathe S; Couper, David J; Comellas, Alejandro P; Wells, J Michael; Peters, Stephen P; Criner, Gerard J; Kanner, Richard E; Paine, Robert; Christenson, Stephanie A; Cooper, Christopher B; Barjaktarevic, Igor Z; Krishnan, Jerry A; Labaki, Wassim W; Han, MeiLan K; Curtis, Jeffrey L; Hansel, Nadia N; Wise, Robert A; Drummond, M Bradley","year":2020,"journal":"Chronic obstructive pulmonary diseases (Miami, Fla.), 7(4), 370-381","doi":"10.15326/jcopdf.7.4.2020.0142","pmid":"33108110","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04685","title":"Ocular surface inflammation induces de novo expression of substance P in the trigeminal primary afferents with large cell bodies.","authors":"Byun, Yong-Soo; Mok, Jee-Won; Chung, So-Hyang; Kim, Hyun-Seung; Joo, Choun-Ki","year":2020,"journal":"Scientific reports, 10(1), 15210","doi":"10.1038/s41598-020-72295-x","pmid":"32939029","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04686","title":"The role of the endogenous neurotransmitters associated with neuropathic pain and in the opioid crisis: The innate pain-relieving system.","authors":"Bán, E Gy; Brassai, A; Vizi, E S","year":2020,"journal":"Brain research bulletin, 155, 129-136","doi":"10.1016/j.brainresbull.2019.12.001","pmid":"31816407","tags":[],"studyType":"review","evidenceStrength":"moderate","keyFinding":"The human body has a sophisticated built-in pain relief system that uses endogenous peptides and neurotransmitters — including enkephalins (met- and leu-enkephalin), β-endorphin, dynorphins, endocannabinoids, noradrenaline, dopamine, serotonin, and ATP — working through multiple receptor types (α2-adrenergic, μ-opioid, and others) to modulate pain signaling.\n\nThe review maps how these natural pain-relieving molecules interact within the descending pain modulation pathways, with particular focus on neuropathic pain caused by nerve injury, diabetes, or chemotherapy. It also examines why excessive exogenous opioid use creates problems through the sympathetic nervous system, contributing to the opioid crisis.\n\nNotably, while the US and Canada experienced a severe opioid crisis, most European countries did not — despite also increasing pain medication use — suggesting that prescribing practices and regulatory frameworks, not just pain prevalence, drive opioid misuse.","whyItMatters":"Understanding the body's natural pain-relieving peptides is essential for developing alternatives to addictive opioids. By mapping how endogenous opioid peptides like enkephalins and endorphins work alongside other neurotransmitters, this review identifies pathways that could be therapeutically enhanced without the addiction risk of exogenous opioids — a critical need given the ongoing opioid crisis.","specificNumbers":"Endogenous pain modulators reviewed: enkephalins, β-endorphin, dynorphins, cannabinoids, noradrenaline, dopamine, serotonin, ATP · Key receptors: α2-adrenergic, μ-opioid · Context: US/Canada opioid crisis vs Europe","methodology":"Narrative review synthesizing published research on endogenous neurotransmitters and neuropeptides involved in pain modulation, with emphasis on their roles in neuropathic pain and the mechanisms by which exogenous opioid overuse leads to adverse effects through sympathetic nervous system activation.","limitations":"This is a narrative review, not a systematic review or meta-analysis. It synthesizes existing literature without new experimental data. The comparison between the US/Canada and European opioid situations is high-level and does not control for the many socioeconomic and regulatory variables that differ between regions."},{"rthcId":"RPEP-04687","title":"Activity of airway antimicrobial peptides against cystic fibrosis pathogens.","authors":"Cabak, Andrea; Hovold, Gisela; Petersson, Ann-Cathrine; Ramstedt, Madeleine; Påhlman, Lisa I","year":2020,"journal":"Pathogens and disease, 78(7)","doi":"10.1093/femspd/ftaa048","pmid":"32857857","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04688","title":"In vitro preconditioning of equine adipose mesenchymal stem cells with prostaglandin E2, substance P and their combination changes the cellular protein secretomics and improves their immunomodulatory competence without compromising stemness.","authors":"Cabezas, J; Rojas, D; Wong, Y; Telleria, F; Manriquez, J; Mançanares, A C F; Rodriguez-Alvarez, L L; Castro, F O","year":2020,"journal":"Veterinary immunology and immunopathology, 228, 110100","doi":"10.1016/j.vetimm.2020.110100","pmid":"32871408","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04689","title":"Novel anti-inflammatory and chondroprotective effects of the human melanocortin MC1 receptor agonist BMS-470539 dihydrochloride and human melanocortin MC3 receptor agonist PG-990 on lipopolysaccharide activated chondrocytes.","authors":"Can, Vedia C; Locke, Ian C; Kaneva, Magdalena K; Kerrigan, Mark J P; Merlino, Francesco; De Pascale, Clara; Grieco, Paolo; Getting, Stephen J","year":2020,"journal":"European journal of pharmacology, 872, 172971","doi":"10.1016/j.ejphar.2020.172971","pmid":"32004526","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04690","title":"GLP-1 receptor agonists and pancreatic safety concerns in type 2 diabetic patients: data from cardiovascular outcome trials.","authors":"Cao, Chuqing; Yang, Shuting; Zhou, Zhiguang","year":2020,"journal":"Endocrine, 68(3), 518-525","doi":"10.1007/s12020-020-02223-6","pmid":"32103407","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Pooling data from 7 cardiovascular outcome trials (CVOTs) enrolling 56,004 type 2 diabetes patients, GLP-1 receptor agonists showed no increased risk of acute pancreatitis (Peto OR 1.05, 95% CI 0.78–1.40, p=0.76) or pancreatic cancer (Peto OR 1.12, 95% CI 0.77–1.63, p=0.56) compared to placebo. Results were robust across sensitivity analyses. A total of 180 cases of acute pancreatitis and 108 cases of pancreatic cancer occurred across all trials, with median follow-up ranging from 1.3 to 5.4 years.","whyItMatters":"Pancreatitis and pancreatic cancer have been the most persistent safety concerns surrounding GLP-1 drugs since their introduction. Early case reports and some observational studies suggested a possible link, leading to FDA safety reviews and widespread patient anxiety. This meta-analysis of the highest-quality evidence available — large randomized controlled trials with tens of thousands of patients — found no signal of increased risk, providing substantial reassurance for the millions of people now taking GLP-1 drugs.","specificNumbers":"n=56,004 patients · 7 CVOTs · 180 pancreatitis cases · 108 pancreatic cancer cases · OR 1.05 for pancreatitis (p=0.76) · OR 1.12 for pancreatic cancer (p=0.56) · Follow-up 1.3–5.4 years","methodology":"Systematic review and meta-analysis of randomized controlled cardiovascular outcome trials (CVOTs) comparing GLP-1 receptor agonists to placebo in type 2 diabetes patients. Databases searched: Medline, Embase, and Cochrane through October 2019. Peto odds ratios were calculated for acute pancreatitis and pancreatic cancer. Sensitivity analyses tested the robustness of findings.","limitations":"Even with 56,004 patients, pancreatic cancer is rare enough (108 total cases) that the study may be underpowered to detect small increases in risk. The median follow-up (up to 5.4 years) may be insufficient to detect cancers with long latency periods. All studies were placebo-controlled add-on designs — patients continued standard diabetes care, so the comparison is GLP-1 RA + standard care vs. placebo + standard care. The analysis doesn't differentiate between specific GLP-1 drugs."},{"rthcId":"RPEP-04691","title":"Cancer neoantigens and immunogenicity: mutation position matters.","authors":"Capietto, Aude-Hélène; Jhunjhunwala, Suchit; Delamarre, Lélia","year":2020,"journal":"Molecular & cellular oncology, 7(3), 1740071","doi":"10.1080/23723556.2020.1740071","pmid":"32391432","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Using mouse vaccination studies, the researchers demonstrated that the position of a mutation within a neoantigen peptide is an important criterion for predicting immunogenicity. While computational methods have made progress in predicting which peptides will be presented by the immune system, understanding which mutated peptides are actually recognized as foreign by T cells has remained a major gap. This work identifies mutation position as a key variable that can improve neoantigen prediction algorithms.","whyItMatters":"Personalized cancer vaccines based on neoantigens are one of the most promising frontiers in oncology, but a major bottleneck is predicting which mutations will actually trigger an immune response. Current algorithms can predict which peptides are presented on cell surfaces but struggle to identify which ones T cells will recognize. Adding mutation position as a predictive factor could significantly improve neoantigen selection, making personalized cancer vaccines more effective.","specificNumbers":"","methodology":"The researchers conducted mouse vaccination studies to examine the features that make cancer neoantigens immunogenic. They analyzed how the position of the mutation within the peptide sequence affects T cell recognition and used these findings to evaluate computational prediction methods for selecting neoantigens for immunotherapy.","limitations":"The abstract provides limited experimental detail, suggesting this may be a brief report or commentary. The findings are based on mouse models, which have different immune repertoires than humans. The specific mutation positions that enhance immunogenicity and the magnitude of the effect are not detailed in the abstract. Translating these findings to human neoantigen prediction would require validation with human T cell data."},{"rthcId":"RPEP-04692","title":"Antimicrobial Effects of Thymosin Beta-4 and Ciprofloxacin Adjunctive Therapy in Pseudomonas aeruginosa Induced Keratitis.","authors":"Carion, Thomas W; Ebrahim, Abdul Shukkur; Alluri, Spandana; Ebrahim, Thanzeela; Parker, Tressa; Burns, Julia; Sosne, Gabriel; Berger, Elizabeth A","year":2020,"journal":"International journal of molecular sciences, 21(18)","doi":"10.3390/ijms21186840","pmid":"32961846","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04693","title":"Vasoactive intestinal peptide axis is dysfunctional in patients with Graves' disease.","authors":"Carrión, M; Ramos-Leví, A M; Seoane, I V; Martínez-Hernández, R; Serrano-Somavilla, A; Castro, D; Juarranz, Y; González-Álvaro, I; Gomariz, Rosa P; Marazuela, Mónica","year":2020,"journal":"Scientific reports, 10(1), 13018","doi":"10.1038/s41598-020-70138-3","pmid":"32747757","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04694","title":"IL-4 induces M2 macrophages to produce sustained analgesia via opioids.","authors":"Celik, Melih Ö; Labuz, Dominika; Keye, Jacqueline; Glauben, Rainer; Machelska, Halina","year":2020,"journal":"JCI insight, 5(4)","doi":"10.1172/jci.insight.133093","pmid":"32102987","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04695","title":"Copy number variation, gene expression and histological localization of human beta-defensin 2 in patients with adeno-tonsillar hypertrophy.","authors":"Celsi, Fulvio; Zupin, Luisa; Athanasakis, Emmanouil; Orzan, Eva; Grasso, Domenico Leonardo; Crovella, Sergio","year":2020,"journal":"Biotechnic & histochemistry : official publication of the Biological Stain Commission, 95(8), 634-640","doi":"10.1080/10520295.2020.1752936","pmid":"32551953","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04696","title":"Obesity, Polycystic Ovary Syndrome, and Infertility: A New Avenue for GLP-1 Receptor Agonists.","authors":"Cena, Hellas; Chiovato, Luca; Nappi, Rossella E","year":2020,"journal":"The Journal of clinical endocrinology and metabolism, 105(8), e2695-709","doi":"10.1210/clinem/dgaa285","pmid":"32442310","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04697","title":"Pharmacological Management of Glucose Dysregulation in Patients Treated with Second-Generation Antipsychotics.","authors":"Cernea, Simona; Dima, Lorena; Correll, Christoph U; Manu, Peter","year":2020,"journal":"Drugs, 80(17), 1763-1781","doi":"10.1007/s40265-020-01393-x","pmid":"32930957","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04698","title":"Intracellular delivery of therapeutic antisense oligonucleotides targeting mRNA coding mitochondrial proteins by cell-penetrating peptides.","authors":"Cerrato, Carmine Pasquale; Kivijärvi, Tove; Tozzi, Roberta; Lehto, Tõnis; Gestin, Maxime; Langel, Ülo","year":2020,"journal":"Journal of materials chemistry. B, 8(47), 10825-10836","doi":"10.1039/d0tb01106a","pmid":"33174901","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04699","title":"Cytosolic delivery of peptidic STAT3 SH2 domain inhibitors.","authors":"Cerulli, Robert A; Shehaj, Livia; Tosic, Isidora; Jiang, Kevin; Wang, Jing; Frank, David A; Kritzer, Joshua A","year":2020,"journal":"Bioorganic & medicinal chemistry, 28(12), 115542","doi":"10.1016/j.bmc.2020.115542","pmid":"32503696","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04700","title":"Effects of estrogen and progesterone on the neurogenic inflammatory neuropeptides: implications for gender differences in migraine.","authors":"Cetinkaya, Ayhan; Kilinc, Erkan; Camsari, Cagri; Ogun, Muhammed Nur","year":2020,"journal":"Experimental brain research, 238(11), 2625-2639","doi":"10.1007/s00221-020-05923-7","pmid":"32924075","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04701","title":"Bioactive peptides from food fermentation: A comprehensive review of their sources, bioactivities, applications, and future development.","authors":"Chai, Kong Fei; Voo, Amanda Ying Hui; Chen, Wei Ning","year":2020,"journal":"Comprehensive reviews in food science and food safety, 19(6), 3825-3885","doi":"10.1111/1541-4337.12651","pmid":"33337042","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04702","title":"Aminoglycosides can be a better choice over macrolides in COVID-19 regimen: Plausible mechanism for repurposing strategy.","authors":"Chalichem, Nehru Sai Suresh; Bethapudi, Bharathi; Mundkinajeddu, Deepak","year":2020,"journal":"Medical hypotheses, 144, 109984","doi":"10.1016/j.mehy.2020.109984","pmid":"32554149","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04703","title":"Alterations in Rat Accumbens Dopamine, Endocannabinoids and GABA Content During WIN55,212-2 Treatment: The Role of Ghrelin.","authors":"Charalambous, Chrysostomos; Lapka, Marek; Havlickova, Tereza; Syslova, Kamila; Sustkova-Fiserova, Magdalena","year":2020,"journal":"International journal of molecular sciences, 22(1)","doi":"10.3390/ijms22010210","pmid":"33379212","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Blocking the ghrelin receptor (GHS-R1A) with the antagonist JMV2959 significantly reduced cannabinoid-induced dopamine release in the nucleus accumbens shell — the brain's reward center and a critical trigger for addiction. JMV2959 pretreatment also attenuated cannabinoid-increased endocannabinoid levels (anandamide and 2-AG), reversed cannabinoid-induced GABA decreases, and reduced cannabinoid-triggered behavioral stimulation. This demonstrates that the ghrelin peptide system significantly participates in the rewarding and reinforcing effects of cannabinoids.","whyItMatters":"Cannabis addiction affects a growing number of people, and there are currently no approved pharmacological treatments. This study reveals that the ghrelin peptide signaling system is a key mediator of cannabinoid reward processing in the brain. Blocking the ghrelin receptor reduced the dopamine surge that drives addiction-related behaviors, suggesting that ghrelin receptor antagonists could become a novel treatment approach for cannabis use disorder.","specificNumbers":"3 mg/kg JMV2959 (GHS-R1A antagonist) · Significant reduction in accumbens dopamine efflux · Attenuated anandamide and 2-AG increases · Reversed GABA decrease · Reduced behavioral stimulation","methodology":"Preclinical study in male Wistar rats. The synthetic cannabinoid WIN55,212-2 was administered into the posterior ventral tegmental area (VTA) to trigger dopamine release. Rats were pretreated with the GHS-R1A antagonist JMV2959 (3 mg/kg i.p.) or vehicle. Dopamine, endocannabinoids (anandamide, 2-AG), and GABA levels in the nucleus accumbens shell were measured using microdialysis. Behavioral effects were assessed using LABORAS automated home cage monitoring.","limitations":"This is an animal study using a synthetic cannabinoid agonist (WIN55,212-2) rather than THC, which may have different pharmacological properties. The study used a single dose of the ghrelin receptor antagonist and did not assess chronic treatment. Results in rats may not directly translate to human cannabinoid addiction. The ghrelin receptor antagonist JMV2959 is a research tool, not a clinical drug."},{"rthcId":"RPEP-04704","title":"A stapled POL κ peptide targets REV1 to inhibit mutagenic translesion synthesis.","authors":"Chatterjee, Nimrat; D'Souza, Sanjay; Shabab, Mohammad; Harris, Cynthia A; Hilinski, Gerard J; Verdine, Gregory L; Walker, Graham C","year":2020,"journal":"Environmental and molecular mutagenesis, 61(8), 830-836","doi":"10.1002/em.22395","pmid":"32573829","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04705","title":"Neuropeptide S promotes wakefulness through the inhibition of sleep-promoting ventrolateral preoptic nucleus neurons.","authors":"Chauveau, Frédéric; Claverie, Damien; Lardant, Emma; Varin, Christophe; Hardy, Eléonore; Walter, Augustin; Canini, Frédéric; Rouach, Nathalie; Rancillac, Armelle","year":2020,"journal":"Sleep, 43(1)","doi":"10.1093/sleep/zsz189","pmid":"31403694","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04706","title":"Combining MALDI mass spectrometry imaging and droplet-base surface sampling analysis for tissue distribution, metabolite profiling, and relative quantification of cyclic peptide melanotan II.","authors":"Chen, Bingming; Vavrek, Marissa; Gundersdorf, Richard; Zhong, Wendy; Cancilla, Mark T","year":2020,"journal":"Analytica chimica acta, 1125, 279-287","doi":"10.1016/j.aca.2020.05.050","pmid":"32674774","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04707","title":"Thymosinβ4 alleviates cholestatic liver fibrosis in mice through downregulating PDGF/PDGFR and TGFβ/Smad pathways.","authors":"Chen, Cai; Li, Xiankui; Wang, Lei","year":2020,"journal":"Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver, 52(3), 324-330","doi":"10.1016/j.dld.2019.08.014","pmid":"31542221","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04708","title":"Development and Challenges of Antimicrobial Peptides for Therapeutic Applications.","authors":"Chen, Charles H; Lu, Timothy K","year":2020,"journal":"Antibiotics (Basel, Switzerland), 9(1)","doi":"10.3390/antibiotics9010024","pmid":"31941022","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04709","title":"DSCAM-AS1 mediates pro-hypertrophy role of GRK2 in cardiac hypertrophy aggravation via absorbing miR-188-5p.","authors":"Chen, Huiqin; Cai, Kefeng","year":2020,"journal":"In vitro cellular & developmental biology. Animal, 56(4), 286-295","doi":"10.1007/s11626-020-00441-w","pmid":"32377998","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04710","title":"Bioactive peptides derived from crimson snapper and in vivo anti-aging effects on fat diet-induced high fat Drosophila melanogaster.","authors":"Chen, Shengyang; Yang, Qian; Chen, Xuan; Tian, Yongqi; Liu, Zhiyu; Wang, Shaoyun","year":2020,"journal":"Food & function, 11(1), 524-533","doi":"10.1039/c9fo01414d","pmid":"31844865","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04711","title":"Personalized neoantigen vaccination with synthetic long peptides: recent advances and future perspectives.","authors":"Chen, Xiaotong; Yang, Ju; Wang, Lifeng; Liu, Baorui","year":2020,"journal":"Theranostics, 10(13), 6011-6023","doi":"10.7150/thno.38742","pmid":"32483434","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Synthetic long peptide (SLP) neoantigen vaccines offer several advantages over traditional short peptide vaccines: they overcome immune tolerance, activate both CD4+ helper and CD8+ killer T cell responses, and target mutations unique to individual tumors rather than shared antigens.\n\nThe review summarizes evidence that extending short peptides (8-10 amino acids) into longer formats (25-35 amino acids) improves antigen processing by professional antigen-presenting cells and generates more robust and durable immune responses. Multiple preclinical and early clinical studies have shown encouraging results with personalized neoantigen peptide vaccines.","whyItMatters":"Cancer immunotherapy has been revolutionized by checkpoint inhibitors, but many patients don't respond. Personalized neoantigen vaccines could complement these treatments by training the immune system to recognize each patient's specific tumor mutations. Long peptide formats are emerging as the preferred delivery platform because they generate broader, more durable immune responses than short peptides — and synthetic peptides are faster and cheaper to manufacture than other vaccine formats.","specificNumbers":"","methodology":"This is a narrative review published in Theranostics that synthesizes the history of peptide-based cancer vaccines, the scientific rationale for using long peptides over short peptides, the advantages of neoantigen targeting, and current preclinical and clinical developments in the field.","limitations":"As a review, no new data is presented. The field is still early-stage — most clinical trials are small, single-arm studies without randomized comparisons. Manufacturing personalized vaccines is time-consuming and expensive. Not all predicted neoantigens generate meaningful immune responses. Tumors can evolve to lose the targeted mutations (immune escape). The optimal adjuvant, dosing schedule, and combination strategies remain undefined."},{"rthcId":"RPEP-04712","title":"A Novel Photoreactive Excipient to Probe Peptide-Matrix Interactions in Lyophilized Solids.","authors":"Chen, Yuan; Topp, Elizabeth M","year":2020,"journal":"Journal of pharmaceutical sciences, 109(1), 709-718","doi":"10.1016/j.xphs.2019.04.024","pmid":"31034909","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Two photoreactive excipient analogs — photo-leucine (pLeu, an amino acid analog) and photo-glucosamine (pGlcN, a sugar analog) — showed distinctly different labeling patterns on salmon calcitonin in lyophilized solids. The extent and specific sites of labeling on the peptide differed between the two probes, demonstrating that ionizable and nonionizable excipients interact with the peptide through different mechanisms.\n\nThe distribution of photo-reaction products was also influenced by the type of unlabeled excipient present (sucrose vs. histidine) and the pre-lyophilization pH (tested from 6 to 9.9), indicating that formulation conditions meaningfully change how excipients contact the peptide in the solid state.","whyItMatters":"Peptide therapeutics are one of the fastest-growing drug categories, but formulating them for stability remains a major challenge. Currently, choosing excipients (stabilizers, bulking agents, buffers) is largely trial-and-error because there have been few tools to directly observe how these molecules interact with peptides in the solid state. This photolytic labeling approach could transform peptide drug formulation into a more rational, evidence-based process — potentially reducing development costs and improving drug shelf life.","specificNumbers":"","methodology":"Researchers incorporated diazirine-derived photoreactive probes — commercially available photo-leucine and custom-synthesized photo-glucosamine — into freeze-dried solids containing salmon calcitonin along with standard excipients (sucrose or histidine). Samples were prepared at pH values ranging from 6 to 9.9 before lyophilization. UV light exposure (365 nm for 30-60 minutes) activated the probes, causing them to form covalent bonds with nearby peptide residues. The resulting labeled products were identified and quantified using liquid chromatography-mass spectrometry.","limitations":"This is a proof-of-concept study using a single model peptide (salmon calcitonin). The photoreactive probes may alter the native interactions they're trying to measure by introducing bulky chemical groups. The UV exposure required could potentially cause photodegradation of the peptide itself. The study demonstrates the method's feasibility but does not yet show it can predict formulation stability or guide real-world drug development decisions."},{"rthcId":"RPEP-04713","title":"Influence of acupuncture on the expression of VIP, SP, NKA and NKB, cAMP/cGMP and HE content and treatment of bronchial asthma in rats.","authors":"Chen, Yujuan; Gao, Yanlu; Lu, Wenwen; Gao, Wei","year":2020,"journal":"Cellular and molecular biology (Noisy-le-Grand, France), 66(5), 29-35","doi":null,"pmid":"33040809","tags":["substance-p","vip","neuropeptides"],"studyType":"animal-study","evidenceStrength":"low","keyFinding":"In a rat model of bronchial asthma, acupuncture altered the levels of several neuropeptides in lung tissue. Asthmatic rats showed decreased vasoactive intestinal peptide (VIP) and cAMP/cGMP ratios alongside increased substance P (SP), neurokinin A (NKA), and neurokinin B (NKB). Acupuncture treatment partially reversed these changes — increasing cAMP/cGMP while decreasing NKA, NKB, and SP — and improved lung tissue pathology.\n\nWhen the adrenal glands were removed before acupuncture, the peptide-level improvements were blunted, suggesting that acupuncture's effects on airway neuropeptides depend partly on intact adrenal (glucocorticoid) function.","whyItMatters":"This study provides mechanistic evidence that neuropeptides like substance P, VIP, and the neurokinins are actively involved in the airway inflammation of asthma — and that their levels can be modulated by external stimulation. Understanding how these peptides contribute to bronchoconstriction and inflammation could inform future peptide-based approaches to respiratory disease.","specificNumbers":"n=50 rats · 5 groups of 10 · Peptides measured: SP, VIP, NKA, NKB · cAMP/cGMP ratio assessed · 5 acupoints stimulated","methodology":"Fifty male Wistar rats were divided into 5 groups: normal control, asthma model, asthma + acupuncture, adrenalectomy + asthma, and adrenalectomy + asthma + acupuncture. Asthma was induced with ovalbumin. Acupuncture was applied at five specific points. Lung tissue was examined with HE staining and immunohistochemistry for SP, VIP, NKA, and NKB. cAMP/cGMP was measured by ELISA.","limitations":"This is an animal study in rats, which may not translate to human asthma. The sample size is small (10 per group). The acupuncture methodology is difficult to blind or standardize, and the study was open-label. No dose-response or time-course data were reported for the peptide changes."},{"rthcId":"RPEP-04714","title":"Antiviral and Immunomodulatory Properties of Antimicrobial Peptides Produced by Human Keratinocytes.","authors":"Chessa, Céline; Bodet, Charles; Jousselin, Clément; Wehbe, Michel; Lévêque, Nicolas; Garcia, Magali","year":2020,"journal":"Frontiers in microbiology, 11, 1155","doi":"10.3389/fmicb.2020.01155","pmid":"32582097","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04715","title":"Calcitonin gene-related peptide (CGRP)-targeted therapies as preventive and acute treatments for migraine-The monoclonal antibodies and gepants.","authors":"Chiang, Chia-Chun; Schwedt, Todd J","year":2020,"journal":"Progress in brain research, 255, 143-170","doi":"10.1016/bs.pbr.2020.06.019","pmid":"33008505","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04716","title":"Modeling the Three-Dimensional Bioprinting Process of β-Sheet Self-Assembling Peptide Hydrogel Scaffolds.","authors":"Chiesa, Irene; Ligorio, Cosimo; Bonatti, Amedeo F; De Acutis, Aurora; Smith, Andrew M; Saiani, Alberto; Vozzi, Giovanni; De Maria, Carmelo","year":2020,"journal":"Frontiers in medical technology, 2, 571626","doi":"10.3389/fmedt.2020.571626","pmid":"35047879","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04717","title":"Application of Dimedone Enamines as Protecting Groups for Amines and Peptides.","authors":"Chithanna, Sivanna; Vyasamudri, Sameer; Yang, Ding-Yah","year":2020,"journal":"Organic letters, 22(6), 2391-2395","doi":"10.1021/acs.orglett.0c00586","pmid":"32148048","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04718","title":"Study of the intracellular delivery mechanism of a pH-sensitive peptide modified with enhanced green fluorescent protein.","authors":"Chiu, Po-Chuan; Hsieh, Pei-Yu; Kang, Jyun-Wei; Chang, Po-Hsun; Shen, Li-Jiuan","year":2020,"journal":"Journal of drug targeting, 28(4), 408-418","doi":"10.1080/1061186X.2019.1669041","pmid":"31524004","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04719","title":"Venom-derived modulators of epilepsy-related ion channels.","authors":"Chow, Chun Yuen; Absalom, Nathan; Biggs, Kimberley; King, Glenn F; Ma, Linlin","year":2020,"journal":"Biochemical pharmacology, 181, 114043","doi":"10.1016/j.bcp.2020.114043","pmid":"32445870","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04720","title":"Long-acting GLP-1RAs: An overview of efficacy, safety, and their role in type 2 diabetes management.","authors":"Chun, Ji Hyun; Butts, Amy","year":2020,"journal":"JAAPA : official journal of the American Academy of Physician Assistants, 33(8), 3-18","doi":"10.1097/01.JAA.0000669456.13763.bd","pmid":"32740121","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04721","title":"Vitamin D-Cathelicidin Axis: at the Crossroads between Protective Immunity and Pathological Inflammation during Infection.","authors":"Chung, Chaeuk; Silwal, Prashanta; Kim, Insoo; Modlin, Robert L; Jo, Eun-Kyeong","year":2020,"journal":"Immune network, 20(2), e12","doi":"10.4110/in.2020.20.e12","pmid":"32395364","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04722","title":"Neurokinin-1 receptor activation is sufficient to restore the hypercapnic ventilatory response in the Substance P-deficient naked mole-rat.","authors":"Clayson, Maxwell S; Devereaux, Maiah E M; Pamenter, Matthew E","year":2020,"journal":"American journal of physiology. Regulatory, integrative and comparative physiology, 318(4), R712-R721","doi":"10.1152/ajpregu.00251.2019","pmid":"31967860","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04723","title":"Efficacy and safety of setmelanotide, an MC4R agonist, in individuals with severe obesity due to LEPR or POMC deficiency: single-arm, open-label, multicentre, phase 3 trials.","authors":"Clément, Karine; van den Akker, Erica; Argente, Jesús; Bahm, Allison; Chung, Wendy K; Connors, Hillori; De Waele, Kathleen; Farooqi, I Sadaf; Gonneau-Lejeune, Julie; Gordon, Gregory; Kohlsdorf, Katja; Poitou, Christine; Puder, Lia; Swain, James; Stewart, Murray; Yuan, Guojun; Wabitsch, Martin; Kühnen, Peter","year":2020,"journal":"The lancet. Diabetes & endocrinology, 8(12), 960-970","doi":"10.1016/S2213-8587(20)30364-8","pmid":"33137293","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In the POMC deficiency trial (n=10): 80% of participants achieved at least 10% weight loss at approximately 1 year. Mean hunger score reduction was -27.1% (p=0.0005).\n\nIn the LEPR deficiency trial (n=11): 45% of participants achieved at least 10% weight loss. Mean hunger score reduction was -43.7% (p<0.0001).\n\nDuring the placebo-controlled withdrawal phase, symptoms returned when patients were switched to placebo, confirming the drug's direct effect. Most common adverse events were injection site reactions and hyperpigmentation (skin darkening). No serious treatment-related adverse events occurred in either trial.","whyItMatters":"Before setmelanotide, people with POMC or LEPR deficiency had no treatment that addressed the root cause of their obesity — a broken melanocortin signaling pathway. These patients experience relentless, overwhelming hunger that no amount of willpower can overcome. Setmelanotide directly activates the downstream receptor, restoring appetite control. This represents one of the clearest examples of precision medicine in obesity treatment.","specificNumbers":"","methodology":"Two single-arm, open-label, multicentre phase 3 trials conducted across 10 hospitals in the US, Canada, and Europe. Patients aged 6+ with confirmed POMC or LEPR deficiency received setmelanotide for 12 weeks. Those with meaningful weight loss entered an 8-week blinded withdrawal (4 weeks drug, 4 weeks placebo), then 32 weeks more of open-label treatment. Primary endpoint: proportion achieving ≥10% weight loss at ~1 year.","limitations":"Very small sample sizes (10 and 11 patients) — inherent to studying extremely rare genetic conditions. The trials were open-label for most of their duration, which could bias weight and hunger assessments. The blinded withdrawal phase was only 8 weeks. Long-term safety data beyond ~1 year was not reported. Skin hyperpigmentation occurred in all POMC patients, reflecting the melanocortin pathway's role in pigmentation."},{"rthcId":"RPEP-04724","title":"Bacillus Subtilis Delays Neurodegeneration and Behavioral Impairment in the Alzheimer's Disease Model Caenorhabditis Elegans.","authors":"Cogliati, Sebastián; Clementi, Victoria; Francisco, Marcos; Crespo, Cira; Argañaraz, Federico; Grau, Roberto","year":2020,"journal":"Journal of Alzheimer's disease : JAD, 73(3), 1035-1052","doi":"10.3233/JAD-190837","pmid":"31884470","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"B. subtilis colonization provided comprehensive protection in multiple C. elegans Alzheimer's models:\n\n- Delayed aging and neuronal deterioration in wild-type worms compared to E. coli-fed controls\n- Alleviated amyloid-β-induced paralysis in transgenic strains CL2120 (Aβ3-42) and GMC101 (Aβ1-42)\n- Protected against behavioral deficits including impaired chemotaxis and decreased body bends in CL2355 worms with pan-neuronal Aβ1-42 expression\n- Restored lifespan of Aβ-expressing worms to levels similar to wild-type worms on standard E. coli diet\n\nCritically, B. subtilis strains deficient in quorum-sensing peptide (CSF) synthesis or gut biofilm formation lost their anti-AD effects, demonstrating that these bacterial peptide-dependent processes are essential for the neuroprotective benefits.","whyItMatters":"There is no effective treatment for Alzheimer's disease, and the gut-brain axis is emerging as a promising therapeutic avenue. This study provides mechanistic evidence that a specific bacterial peptide — the quorum-sensing factor CSF — mediates probiotic neuroprotection against amyloid-β toxicity. This moves the conversation beyond general 'gut health' claims to identify a specific peptide-dependent mechanism that could be targeted therapeutically.","specificNumbers":"","methodology":"The researchers used multiple transgenic C. elegans strains expressing human amyloid-β peptides (Aβ1-42 and Aβ3-42) in muscle or neurons. Worms were colonized with B. subtilis (probiotic) or E. coli OP50 (standard non-probiotic food). Assessments included paralysis rates, chemotaxis behavior, body bend frequency, lifespan, aging progression, and neuronal integrity. B. subtilis mutants deficient in CSF synthesis or biofilm formation were used to identify the molecular mechanisms underlying the protective effects.","limitations":"C. elegans is an extremely simple organism — a worm with 302 neurons — and results may not translate to human Alzheimer's disease. The amyloid-β expression models in C. elegans don't replicate the full complexity of human AD pathology (tau tangles, neuroinflammation, vascular changes). Whether B. subtilis can colonize the human gut effectively and produce sufficient CSF to affect brain function is unknown. The study does not demonstrate direct CSF entry into the nervous system."},{"rthcId":"RPEP-04725","title":"Significance of the orexinergic system in modulating stress-related responses in an animal model of post-traumatic stress disorder.","authors":"Cohen, Shlomi; Matar, Michael A; Vainer, Ella; Zohar, Joseph; Kaplan, Zeev; Cohen, Hagit","year":2020,"journal":"Translational psychiatry, 10(1), 10","doi":"10.1038/s41398-020-0698-9","pmid":"32066707","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04726","title":"Optimization of linear and cyclic peptide inhibitors of KEAP1-NRF2 protein-protein interaction.","authors":"Colarusso, Stefania; De Simone, Daniele; Frattarelli, Tommaso; Andreini, Matteo; Cerretani, Mauro; Missineo, Antonino; Moretti, Daniele; Tambone, Sara; Kempf, Georg; Augustin, Martin; Steinbacher, Stefan; Munoz-Sanjuan, Ignacio; Park, Larry; Summa, Vincenzo; Tomei, Licia; Bresciani, Alberto; Dominguez, Celia; Toledo-Sherman, Leticia; Bianchi, Elisabetta","year":2020,"journal":"Bioorganic & medicinal chemistry, 28(21), 115738","doi":"10.1016/j.bmc.2020.115738","pmid":"33065433","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04727","title":"Medial Prefrontal Cortex Neural Plasticity, Orexin Receptor 1 Signaling, and Connectivity with the Lateral Hypothalamus Are Necessary in Cue-Potentiated Feeding.","authors":"Cole, Sindy; Keefer, Sara E; Anderson, Lauren C; Petrovich, Gorica D","year":2020,"journal":"The Journal of neuroscience : the official journal of the Society for Neuroscience, 40(8), 1744-1755","doi":"10.1523/JNEUROSCI.1803-19.2020","pmid":"31953368","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04728","title":"Natural α,β-unsaturated lactones inhibit neuropeptide-induced mast cell activation in an in vitro model of neurogenic inflammation.","authors":"Coll, Roberto Carlos; Vargas, Patricia María; Mariani, María Laura; Penissi, Alicia Beatriz","year":2020,"journal":"Inflammation research : official journal of the European Histamine Research Society ... [et al.], 69(10), 1039-1051","doi":"10.1007/s00011-020-01380-8","pmid":"32666125","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Substance P and neurotensin both induced dose-dependent serotonin release from rat peritoneal mast cells, while neuromedin-N did not. Two natural α,β-unsaturated lactones — dehydroleucodine and xanthatin — inhibited this neuropeptide-induced serotonin release, while a third compound (3-benzyloxymethyl-5H-furan-2-one) did not.\n\nNotably, dehydroleucodine and xanthatin showed higher inhibitory potency than the reference anti-allergy compounds ketotifen and sodium chromoglycate when mast cells were pretreated before neuropeptide exposure. This represents the first evidence that these compounds can block neuropeptide-specific mast cell activation, distinct from their previously known effects on other degranulation pathways.","whyItMatters":"Neurogenic inflammation — where nerves and immune cells amplify each other's signals — drives conditions like chronic pain, migraines, and irritable bowel syndrome. Current treatments for mast cell activation are limited in effectiveness. Finding natural compounds that specifically block the neuropeptide-mast cell interaction could lead to new therapies for these difficult-to-treat conditions.","specificNumbers":"","methodology":"In vitro study using rat peritoneal mast cells. Cells were exposed to neuropeptides (substance P, neurotensin, neuromedin-N) at various concentrations to induce serotonin release. The three lactone compounds were tested as pretreatments and compared against reference anti-allergy drugs (ketotifen and sodium chromoglycate). Serotonin release was measured as the primary outcome of mast cell degranulation.","limitations":"This was an in vitro study using isolated rat mast cells, which may not fully represent the complex in vivo environment of neurogenic inflammation. The compounds were not tested in animal pain models. Human mast cell responses may differ from rat peritoneal mast cells. Pharmacokinetic properties (absorption, metabolism, toxicity) of these lactones were not assessed."},{"rthcId":"RPEP-04729","title":"Kisspeptin enhances brain responses to olfactory and visual cues of attraction in men.","authors":"Comninos, Alexander N; Demetriou, Lysia; Wall, Matthew B; Shah, Amar J; Clarke, Sophie A; Narayanaswamy, Shakunthala; Neher, Asija; Dodge, John A; Bloom, Stuart R; Dhillo, Waljit S","year":2020,"journal":"JCI insight, 5(3)","doi":"10.1172/jci.insight.133633","pmid":"32051344","tags":["neuropeptides"],"studyType":"human-rct","evidenceStrength":"moderate","keyFinding":"In 33 healthy men, kisspeptin enhanced limbic brain activity (amygdala, caudate, putamen, thalamus) to olfactory and visual attraction cues, enhanced penile tumescence, and increased attraction scores.","whyItMatters":"Expands kisspeptin's role beyond explicit sexual stimuli to broader attraction processing, suggesting it modulates fundamental mate-selection brain circuits.","specificNumbers":"33 healthy men; enhanced amygdala, caudate, putamen, thalamus activity; increased penile tumescence and attraction scores","methodology":"Double-blind, placebo-controlled, 2-way crossover fMRI study in 33 healthy heterosexual men.","limitations":"Male participants only. Healthy men, not HSDD patients. Single-session design."},{"rthcId":"RPEP-04730","title":"Thymosin β4 cytoplasmic/nuclear translocation as a new marker of cellular stress. A Caco2 case study.","authors":"Coni, Pierpaolo; Piras, Monica; Mateddu, Anna; Piludu, Marco; Orru, Germano; Scano, Alessandra; Cabras, Tiziana; Piras, Valentina; Lachowicz, Joanna Izabela; Jaremko, Mariusz; Faa, Gavino; Castagnola, Massimo; Pichiri, Giuseppina","year":2020,"journal":"RSC advances, 10(21), 12680-12688","doi":"10.1039/c9ra10365a","pmid":"35497634","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04731","title":"Isolation and characterization of cytotoxic and insulin-releasing components from the venom of the black-necked spitting cobra Naja nigricollis (Elapidae).","authors":"Conlon, J M; Attoub, Samir; Musale, Vishal; Leprince, Jérôme; Casewell, Nicholas R; Sanz, Libia; Calvete, Juan J","year":2020,"journal":"Toxicon: X, 6, 100030","doi":"10.1016/j.toxcx.2020.100030","pmid":"32550585","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Four three-finger toxin peptides from N. nigricollis venom showed cytotoxic activity. Cytotoxin-1N was most potent: LC50 = 0.8 μM (A549 lung cancer), 7 μM (MDA-MB-231 breast cancer), 9 μM (HT-29 colorectal cancer). However, all peptides were also cytotoxic to normal HUVEC endothelial cells (LC50 2-22 μM), and cytotoxin-2N was moderately hemolytic (LC50 45 μM). Separately, two phospholipase A2 isoforms stimulated insulin release approximately 6-fold from BRIN-BD11 beta-cells at 1 μM — a non-cytotoxic concentration.","whyItMatters":"This study highlights both the promise and challenge of venom-derived therapeutics. The potent anti-cancer activity (0.8 μM against lung cancer) shows these peptides are powerful cell killers, but their lack of selectivity for cancer over normal cells is a common problem with venom cytotoxins. The insulin-releasing discovery is potentially more translatable, as it works at non-toxic concentrations — representing a genuinely novel mechanism for stimulating insulin that could complement existing diabetes therapies.","specificNumbers":"","methodology":"Venom from N. nigricollis was fractionated using reversed-phase HPLC. Peptides were identified as three-finger toxins by ESI-MS/MS sequencing of tryptic fragments. Cytotoxicity was tested against three human tumor cell lines (A549, MDA-MB-231, HT-29), normal HUVEC cells, and BRIN-BD11 rat beta-cells. Hemolytic activity was tested against mouse erythrocytes. Insulin-releasing proteins were identified as phospholipase A2 isoforms and tested for insulin stimulation at non-cytotoxic concentrations.","limitations":"In vitro study only — no animal or human testing. The cytotoxic peptides lack cancer selectivity, killing normal endothelial cells at similar concentrations. BRIN-BD11 cells are a rat beta-cell line that may not perfectly replicate human pancreatic islet responses. The insulin-releasing proteins are phospholipases, not peptides per se, which complicates their development as therapeutics due to size and immunogenicity. The concentration producing 6-fold insulin release (1 μM) may be difficult to achieve systemically without toxicity."},{"rthcId":"RPEP-04732","title":"Defensins: Transcriptional regulation and function beyond antimicrobial activity.","authors":"Contreras, Gabriela; Shirdel, Iman; Braun, Markus Santhosh; Wink, Michael","year":2020,"journal":"Developmental and comparative immunology, 104, 103556","doi":"10.1016/j.dci.2019.103556","pmid":"31747541","tags":[],"studyType":"review","evidenceStrength":"review","keyFinding":"Defensins — one of the largest families of antimicrobial peptides — do far more than kill pathogens. This review reveals that defensins also function as immunomodulators (shaping immune responses) and immune cell attractors (recruiting defensive cells to infection sites). These peptides are found across animals, plants, and fungi, and can be expressed either constantly or ramped up in response to infection.\n\nThe review maps the signaling pathways that control defensin gene expression, showing how pattern-recognition receptors detect pathogen-associated molecular patterns (PAMPs) and trigger transcription factor activation to produce defensins. Understanding these trigger mechanisms may reveal additional defensin functions beyond what's currently known.","whyItMatters":"Defensins have traditionally been studied as direct microbial killers, but this review consolidates evidence that they play much broader roles in immunity. By cataloging the signals that turn defensin genes on, the review opens the door to potentially manipulating defensin production for therapeutic purposes — boosting natural defenses against infection or harnessing their immunomodulatory properties.","specificNumbers":"Defensins are one of the largest groups of antimicrobial peptides · Found in animals, plants, and fungi · Focus on human, fish, and marine invertebrate defensins","methodology":"This is a narrative review article that synthesizes published research on defensin transcriptional regulation, expression patterns, and non-antimicrobial functions across species, with a primary focus on human, fish, and marine invertebrate defensins.","limitations":"As a review, this paper synthesizes existing research rather than presenting new experimental data. The broad cross-species scope (humans, fish, marine invertebrates, plants, fungi) means coverage of any single species may lack depth. The abstract doesn't indicate systematic review methodology or quantitative analysis of the evidence base."},{"rthcId":"RPEP-04733","title":"Identification and Optimization of Pyrrolidine Derivatives as Highly Potent Ghrelin Receptor Full Agonists.","authors":"Cooper, Martin; Llinas, Antonio; Hansen, Peter; Caffrey, Moya; Ray, Asim; Sjödin, Stina; Shamovsky, Igor; Wada, Hiroki; Jellesmark Jensen, Tina; Sivars, Ulf; Hultin, Leif; Andersson, Ulf; Lundqvist, Sara; Gedda, Karin; Jinton, Lisa; Krutrök, Nina; Lewis, Richard; Jansson, Paul; Gardelli, Cristina","year":2020,"journal":"Journal of medicinal chemistry, 63(17), 9705-9730","doi":"10.1021/acs.jmedchem.0c00828","pmid":"32787075","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04734","title":"Overexpression of neuropeptide Y decreases responsiveness to neuropeptide Y.","authors":"Corder, Katelynn M; Li, Qin; Cortes, Mariana A; Bartley, Aundrea F; Davis, Taylor R; Dobrunz, Lynn E","year":2020,"journal":"Neuropeptides, 79, 101979","doi":"10.1016/j.npep.2019.101979","pmid":"31708112","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04735","title":"Growth hormone secretagogue receptor in dopamine neurons controls appetitive and consummatory behaviors towards high-fat diet in ad-libitum fed mice.","authors":"Cornejo, María Paula; Barrile, Franco; Cassano, Daniela; Aguggia, Julieta Paola; García Romero, Guadalupe; Reynaldo, Mirta; Andreoli, María Florencia; De Francesco, Pablo Nicolás; Perello, Mario","year":2020,"journal":"Psychoneuroendocrinology, 119, 104718","doi":"10.1016/j.psyneuen.2020.104718","pmid":"32535402","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"DAT-GHSR mice (ghrelin receptor expression limited to dopamine neurons) showed: (1) c-Fos activation in dopamine-containing brain areas after ghrelin treatment, similar to wild-type mice; (2) normal anticipatory activity to scheduled high-fat diet exposure; (3) full binge-like high-fat intake comparable to wild-type mice. However, they did NOT show: increased food intake or locomotor activity in response to systemic or central ghrelin administration. GHSR-deficient mice showed impaired anticipatory activity and binge eating. Conclusion: GHSR in dopamine neurons is sufficient for hedonic high-fat eating but insufficient for ghrelin's homeostatic orexigenic effects.","whyItMatters":"Understanding that ghrelin acts on dopamine neurons specifically to drive pleasure-based eating of fatty food — independent of actual hunger — has profound implications for obesity and eating disorders. It suggests that blocking ghrelin's action on the reward system could reduce binge eating and cravings for unhealthy food without necessarily affecting normal hunger signaling.","specificNumbers":"","methodology":"Genetic approach using crossed reactivable GHSR-deficient mice with DAT-Cre mice to generate mice with ghrelin receptor expression exclusively on dopamine neurons (DAT-GHSR). Tested ghrelin-induced food intake, locomotor activity, c-Fos brain mapping, anticipatory activity to scheduled high-fat diet, and binge-like eating protocols. Compared DAT-GHSR, wild-type, and GHSR-deficient mice.","limitations":"This is a mouse study using genetic manipulations that create an artificial situation (receptor expression only in one neuron type). The binge-eating protocols are standardized models that simplify complex human eating behaviors. The study used only male mice; sex differences in ghrelin signaling are well-documented. Translation to human eating disorders requires caution."},{"rthcId":"RPEP-04736","title":"Development of potent CPP6-gemcitabine conjugates against human prostate cancer cell line (PC-3).","authors":"Correia, Cristiana; Xavier, Cristina P R; Duarte, Diana; Ferreira, Abigail; Moreira, Sara; Vasconcelos, M Helena; Vale, Nuno","year":2020,"journal":"RSC medicinal chemistry, 11(2), 268-273","doi":"10.1039/c9md00489k","pmid":"33479633","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04737","title":"Appetite Control across the Lifecourse: The Acute Impact of Breakfast Drink Quantity and Protein Content. The Full4Health Project.","authors":"Crabtree, Daniel R; Buosi, William; Fyfe, Claire L; Horgan, Graham W; Manios, Yannis; Androutsos, Odysseas; Giannopoulou, Angeliki; Finlayson, Graham; Beaulieu, Kristine; Meek, Claire L; Holst, Jens J; Van Norren, Klaske Van; Mercer, Julian G; Johnstone, Alexandra M","year":2020,"journal":"Nutrients, 12(12)","doi":"10.3390/nu12123710","pmid":"33266325","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04738","title":"Vitamin D Deficiency and Air Pollution Exacerbate COVID-19 Through Suppression of Antiviral Peptide LL37.","authors":"Crane-Godreau, Mardi A; Clem, Kathleen J; Payne, Peter; Fiering, Steven","year":2020,"journal":"Frontiers in public health, 8, 232","doi":"10.3389/fpubh.2020.00232","pmid":"32671009","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04739","title":"Evaluation of Injectable Naloxone-Releasing Hydrogels.","authors":"Crowe, Kaytlyn M; Siddiqui, Zain; Harbour, Victoria; Kim, KaKyung; Syed, Shareef; Paul, Reshma; Roy, Abhishek; Naik, Ruhi; Mitchell, Kayla; Mahajan, Aryan; Sarkar, Biplab; Kumar, Vivek A","year":2020,"journal":"ACS applied bio materials, 3(11), 7858-7864","doi":"10.1021/acsabm.0c01016","pmid":"35019526","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04740","title":"Safety, Tolerability and Pharmacokinetics of Single Dose Polyethylene Glycolated Exenatide Injection (PB-119) in Healthy Volunteers.","authors":"Cui, Hong; Zhao, Cai-Yun; Lv, Yuan; Wei, Min-Ji; Zhu, Yan; Li, Yun; Xia, Ya-Hong; Liu, Yan; Tian, Ji-Hong; Zhang, Pu","year":2020,"journal":"European journal of drug metabolism and pharmacokinetics, 45(3), 361-369","doi":"10.1007/s13318-020-00605-9","pmid":"32006325","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04741","title":"Stapled Peptides Based on Human Angiotensin-Converting Enzyme 2 (ACE2) Potently Inhibit SARS-CoV-2 Infection In Vitro.","authors":"Curreli, Francesca; Victor, Sofia M B; Ahmed, Shahad; Drelich, Aleksandra; Tong, Xiaohe; Tseng, Chien-Te K; Hillyer, Christopher D; Debnath, Asim K","year":2020,"journal":"mBio, 11(6)","doi":"10.1128/mBio.02451-20","pmid":"33310780","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Researchers designed four double-stapled peptides based on the ACE2 receptor helix that SARS-CoV-2 uses to enter human cells. Three of four showed potent antiviral activity with IC50 values of 1.9–4.1 μM in ACE2-overexpressing cells. The most effective peptide, NYBSP-1, completely prevented viral damage at 17.2 μM against authentic SARS-CoV-2. The stapled peptides achieved 50–94% helicity versus only 19% for the linear control, and showed no cytotoxicity. Lead peptide NYBSP-4 demonstrated a plasma half-life exceeding 289 minutes.","whyItMatters":"This work demonstrates a peptide-based strategy for blocking viral entry by mimicking the host receptor. The stapling technique stabilized the peptide structure, dramatically improving both antiviral activity and resistance to degradation — showcasing a generalizable approach for designing therapeutic peptides against emerging viruses.","specificNumbers":"IC50: 1.9–4.1 μM · IC100: 17.2 μM (NYBSP-1) · 50–94% helicity · 19% helicity (linear control) · T1/2 >289 min plasma stability · no cytotoxicity","methodology":"Four double-stapled peptides were designed based on the ~30 amino acid ACE2 binding helix. Helicity was measured by circular dichroism. Antiviral activity was tested using pseudovirus assays in HT1080/ACE2 and A549/ACE2 cells, then validated against authentic SARS-CoV-2 (US_WA-1/2020) in Vero E6 cells. Cytotoxicity and proteolytic stability in human plasma were also assessed.","limitations":"All testing was in vitro (cell cultures); no animal or human studies were conducted. The IC50 values are in the micromolar range, which may present challenges for achieving therapeutic concentrations in vivo. The study was conducted early in the pandemic with the original SARS-CoV-2 strain; effectiveness against later variants is unknown."},{"rthcId":"RPEP-04742","title":"The adjuvant effect of melanin is superior to incomplete Freund's adjuvant in subunit/peptide vaccines in mice.","authors":"Cuzzubbo, Stefania; Banissi, Claire; Rouchon, Marie Sophie; Tran, Thi; Tanchot, Corinne; Tartour, Eric; Carpentier, Antoine F","year":2020,"journal":"Cancer immunology, immunotherapy : CII, 69(12), 2501-2512","doi":"10.1007/s00262-020-02631-7","pmid":"32561966","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04743","title":"Increased expression of the mitochondrial derived peptide, MOTS-c, in skeletal muscle of healthy aging men is associated with myofiber composition.","authors":"D'Souza, Randall F; Woodhead, Jonathan S T; Hedges, Christopher P; Zeng, Nina; Wan, Junxiang; Kumagai, Hiroshi; Lee, Changhan; Cohen, Pinchas; Cameron-Smith, David; Mitchell, Cameron J; Merry, Troy L","year":2020,"journal":"Aging, 12(6), 5244-5258","doi":"10.18632/aging.102944","pmid":"32182209","tags":[],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"MOTS-c, a mitochondrial-derived peptide, shows opposite age-related patterns in blood versus muscle. Circulating MOTS-c in plasma decreased with age, but muscle MOTS-c expression was approximately 1.5 times higher in older (70–81 years) and middle-aged (45–55 years) men compared to young men (18–30 years).\n\nThe increase in muscle MOTS-c was associated with slow-type muscle fiber markers, consistent with the well-known fast-to-slow fiber type transition that occurs with aging. In older men, higher muscle MOTS-c was associated with better muscle quality (maximal leg-press strength relative to thigh cross-sectional area).\n\nThe study also found evidence that MOTS-c transcription may be regulated independently of the full-length 12S rRNA gene it sits within, and that its expression in human muscle is not linked to antioxidant response element (ARE) genes as previously seen in cell culture.","whyItMatters":"MOTS-c has been called an 'exercise mimetic' peptide and is being studied as a potential anti-aging molecule. This study provides the first detailed look at how MOTS-c behaves in actual human muscle tissue as people age. The finding that muscle MOTS-c increases with age — while blood levels decrease — suggests the peptide may play a compensatory protective role in aging muscle, potentially helping maintain muscle quality even as fiber types shift.","specificNumbers":"3 age groups: young (18–30), middle-aged (45–55), older (70–81) · ~1.5-fold higher muscle MOTS-c in older/middle-aged vs young · Plasma MOTS-c decreased with age · Muscle MOTS-c correlated with muscle quality in older men","methodology":"Cross-sectional study in healthy men across three age groups. Researchers measured MOTS-c levels in both blood plasma and skeletal muscle tissue, along with markers of muscle fiber type, muscle quality (leg press strength/thigh cross-sectional area), and gene expression using small RNA assays and transcriptome analysis.","limitations":"Cross-sectional design — showing associations at a point in time, not causation over time. Small sample (specific n not stated). Only men were included. The study cannot determine whether increased muscle MOTS-c is protective or merely a byproduct of fiber type transition. Cell culture findings about MOTS-c and antioxidant genes did not replicate in human muscle, raising questions about translating in vitro MOTS-c research to humans."},{"rthcId":"RPEP-04744","title":"Otoprotective Effect of Cortexin, Cogitum, and Elkar Administered Simultaneously with Netromycin in the Experiment.","authors":"D'yakonova, I N; Ishanova, Yu S; Rakhmanova, I V","year":2020,"journal":"Bulletin of experimental biology and medicine, 169(4), 458-462","doi":"10.1007/s10517-020-04908-4","pmid":"32894392","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04745","title":"Antiretroviral and cytotoxic activities of Tityus obscurus synthetic peptide.","authors":"da Mata, Elida C G; Ombredane, Alicia; Joanitti, Graziella A; Kanzaki, L I B; Schwartz, Elisabeth F","year":2020,"journal":"Archiv der Pharmazie, 353(11), e2000151","doi":"10.1002/ardp.202000151","pmid":"32686134","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04746","title":"Influence of pain-relieving therapies on inflammation and the expression of proinflammatory neuropeptides after dental bleaching treatment.","authors":"da Silva, Livia Maria Alves Valentim; Cintra, Luciano Tavares Angelo; Gallinari, Marjorie de Oliveira; Benetti, Francine; Rahal, Vanessa; Ervolino, Edilson; de Alcântara, Sibele; Briso, André Luiz Fraga","year":2020,"journal":"Restorative dentistry & endodontics, 45(2), e20","doi":"10.5395/rde.2020.45.e20","pmid":"32483537","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 72 rats divided into 6 treatment groups, dental bleaching increased inflammation and expression of the neuropeptides substance P and calcitonin gene-related peptide (CGRP) in pulp nerve fibers. These markers decreased naturally over 48 hours across all bleaching groups.\n\nRats treated with a topical desensitizing agent (potassium nitrate/sodium fluoride) before bleaching showed significantly better outcomes within 24 hours compared to untreated bleached animals. Ibuprofen administered before and after bleaching (and every 12 hours thereafter) did not show the same positive effects on neuropeptide expression, suggesting the desensitizing gel more effectively targets nerve-level inflammation.","whyItMatters":"Tooth sensitivity is the most common side effect of dental bleaching and a major reason patients avoid or discontinue treatment. By showing that desensitizing gels reduce not just symptoms but the underlying neuropeptide-driven inflammatory response, this study provides biological evidence supporting their clinical use and suggests they work at a deeper mechanistic level than simple surface desensitization.","specificNumbers":"","methodology":"Seventy-two rats were divided into 6 groups: control, bleaching only, ibuprofen only, ibuprofen with bleaching, desensitizing agent only, and desensitizing agent with bleaching. Placebo gel was applied to the left jaw and bleaching agent to the right jaw. Each group was subdivided for analysis at 0, 24, and 48 hours post-bleaching (n=8 per subgroup). After euthanasia, maxillae were processed for histopathological analysis (inflammation grading) and immunohistochemistry (substance P and CGRP expression). Data were analyzed using Kruskal-Wallis and Dunn tests with significance set at p < 0.05.","limitations":"This is an animal study using rats, whose dental anatomy and pain responses differ from humans. The study measured neuropeptide expression through immunohistochemistry, which shows presence but not exact quantities. The 48-hour observation window may not capture longer-term effects. Clinical translation to human bleaching protocols requires further validation. The specific desensitizing gel formulation may not represent all commercial products."},{"rthcId":"RPEP-04747","title":"Technological challenges in the preclinical development of an HIV nanovaccine candidate.","authors":"Dacoba, Tamara G; Ruiz-Gatón, Luisa; Benito, Ana; Klein, Marlène; Dupin, Damien; Luo, Ma; Menta, Mathieu; Teijeiro-Osorio, Desirée; Loinaz, Iraida; Alonso, María J; Crecente-Campo, José","year":2020,"journal":"Drug delivery and translational research, 10(3), 621-634","doi":"10.1007/s13346-020-00721-8","pmid":"32040775","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Researchers rigorously characterized a peptide-based nanovaccine candidate for HIV/SIV prevention consisting of chitosan/dextran sulfate nanoparticles loaded with twelve SIV peptide antigens. Using a quality-by-design approach, they validated particle size characterization across three complementary techniques and confirmed inter-batch reproducibility across three independent laboratories.\n\nThe nanoformulation demonstrated long-term stability and scalable manufacturing. Combined with previously reported in vivo efficacy in macaque models, these results position the peptide nanovaccine as a viable candidate for advancement to clinical trials.","whyItMatters":"Despite decades of research, an HIV vaccine remains elusive. This peptide-based nanovaccine approach addresses both the scientific challenge (using multiple peptide antigens for broad immune coverage) and a critical practical barrier — the 'death valley' between promising lab results and reliable, scalable manufacturing. By demonstrating reproducibility across multiple labs and long-term stability, this work moves a peptide HIV vaccine closer to clinical reality.","specificNumbers":"12 SIV peptide antigens · 3 independent labs validated reproducibility · Multiple characterization techniques (DLS, NTA, electron microscopy) · Long-term stability confirmed · Previous macaque efficacy demonstrated","methodology":"Researchers characterized chitosan/dextran sulfate nanoparticles loaded with a specific SIV peptide antigen using a quality-by-design approach. Particle size was measured by dynamic light scattering, nanoparticle tracking analysis, and electron microscopy. Inter-batch reproducibility was validated across three independent laboratories. Long-term storage stability and manufacturing scalability were assessed.","limitations":"This study focused on characterization and manufacturing quality rather than new immunological data. The in vivo efficacy referenced was from a previous macaque study (SIV model), not human HIV trials. Only one of the twelve peptide antigens was characterized in detail in this work. The translation from SIV protection in macaques to HIV protection in humans is notoriously challenging. Clinical trial data is not yet available."},{"rthcId":"RPEP-04748","title":"Thymosin β4 Identified by Transcriptomic Analysis from HF Anagen to Telogen Promotes Proliferation of SHF-DPCs in Albas Cashmere Goat.","authors":"Dai, Bai; Hao, Fei; Xu, Teng; Zhu, Bing; Ren, Li-Qing; Han, Xiao-Yu; Liu, Dong-Jun","year":2020,"journal":"International journal of molecular sciences, 21(7)","doi":"10.3390/ijms21072268","pmid":"32218218","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Through transcriptomic analysis comparing the growth phase (anagen) and resting phase (telogen) of cashmere goat hair follicles, researchers identified Thymosin β4 (Tβ4) as a key differentially expressed gene with higher expression during the active growth phase.\n\nFunctional validation showed that overexpressing Tβ4 promoted the proliferation of secondary hair follicle dermal papilla cells (SHF-DPCs), while silencing Tβ4 inhibited their proliferation. This establishes Tβ4 as a functional regulator of hair follicle cell growth.","whyItMatters":"Thymosin β4 is one of the most studied peptides for tissue repair and regeneration, and its role in hair growth has attracted attention for potential human hair loss treatments. This study provides additional mechanistic evidence that Tβ4 directly promotes hair follicle cell proliferation, supporting its potential therapeutic application.","specificNumbers":"","methodology":"Researchers analyzed RNA sequencing datasets from skin and dermal papilla cells of cashmere goats at different hair cycle stages. They identified differentially expressed genes, performed functional enrichment and protein-protein interaction network analysis, and validated the top candidate (Thymosin β4) through overexpression and silencing experiments in cultured dermal papilla cells.","limitations":"This study was conducted in cashmere goats, and results may not directly translate to human hair biology despite conserved Tβ4 function across species. The experiments were in vitro (cultured cells), not in living animals receiving Tβ4 treatment. The study focused on cell proliferation only, without assessing actual hair fiber production or quality."},{"rthcId":"RPEP-04749","title":"Sodium butyrate promotes lipopolysaccharide-induced innate immune responses by enhancing mitogen-activated protein kinase activation and histone acetylation in bovine mammary epithelial cells.","authors":"Dai, Hongyu; Wei, Guozhen; Wang, Yan; Ma, Nana; Chang, Guangjun; Shen, Xiangzhen","year":2020,"journal":"Journal of dairy science, 103(12), 11636-11652","doi":"10.3168/jds.2020-18198","pmid":"33010913","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04750","title":"Hemokinin-1 and substance P stimulate production of inflammatory cytokines and chemokines in human colonic mucosa via both NK1 and NK2 tachykinin receptors.","authors":"Dai, Liying; Perera, D Shevy; Burcher, Elizabeth; Liu, Lu","year":2020,"journal":"Neuropeptides, 82, 102061","doi":"10.1016/j.npep.2020.102061","pmid":"32600668","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"When human colonic mucosal tissue was exposed to hemokinin-1 (HK-1) at 0.1 μM for 4 hours, it significantly increased both gene expression and release of multiple inflammatory mediators: MCP-1, MIP-1α, MIP-1β, RANTES, TNF-α, IL-1β, and IL-6.\n\nSubstance P (SP) at the same concentration produced comparable effects on most mediators but notably did not affect MCP-1 or RANTES — indicating HK-1 has a broader pro-inflammatory profile than SP in the human colon.\n\nBoth NK1 receptor antagonist SR140333 and NK2 receptor antagonist SR48968 (each at 0.1 μM) separately inhibited these inflammatory responses, demonstrating that both receptor types mediate the effects. This dual-receptor involvement was a novel finding and suggests HK-1 may also signal through additional tachykinin-preferring receptors.","whyItMatters":"Inflammatory bowel disease (IBD) affects millions of people, and understanding what drives gut inflammation is essential for developing better treatments. This study reveals that HK-1, a peptide primarily from immune cells, may be an important inflammatory driver in the colon — potentially even more so than the better-known substance P. Since both peptides work through identifiable receptors, this opens the door to developing receptor-blocking drugs that could calm gut inflammation.","specificNumbers":"","methodology":"The researchers used human colonic mucosal explants — tissue samples taken from human colons — and incubated them with HK-1 or substance P at 0.1 μM for 4 hours. They measured inflammatory cytokine and chemokine production at both the gene expression level (using QuantiGene assay) and the protein release level (using Procarta multiplex assay). To determine which receptors were involved, they pre-treated tissue with selective NK1 (SR140333) or NK2 (SR48968) receptor antagonists before peptide exposure.","limitations":"This is an ex vivo study using isolated tissue explants, which may not fully represent the complex in vivo environment of the gut. The tissue was exposed to peptides for only 4 hours, so longer-term effects are unknown. The sample size and donor demographics are not fully detailed in the abstract. The study does not include tissue from IBD patients, so the relevance to active disease is inferred rather than directly demonstrated. Concentration tested (0.1 μM) may not reflect physiological levels."},{"rthcId":"RPEP-04751","title":"Exploratory open-label clinical study to determine the S-588410 cancer peptide vaccine-induced tumor-infiltrating lymphocytes and changes in the tumor microenvironment in esophageal cancer patients.","authors":"Daiko, H; Marafioti, T; Fujiwara, T; Shirakawa, Y; Nakatsura, T; Kato, K; Puccio, I; Hikichi, T; Yoshimura, S; Nakagawa, T; Furukawa, M; Stoeber, K; Nagira, M; Ide, N; Kojima, T","year":2020,"journal":"Cancer immunology, immunotherapy : CII, 69(11), 2247-2257","doi":"10.1007/s00262-020-02619-3","pmid":"32500232","tags":[],"studyType":"clinical-trial","evidenceStrength":"preliminary","keyFinding":"The cancer peptide vaccine S-588410 — containing five HLA-A*24:02-restricted peptides derived from cancer testis antigens — successfully induced tumor-specific immune responses in all 15 esophageal cancer patients. After vaccination, tumor tissue showed increased densities of CD8+ T-cells, CD8+ granzyme B+ cells (indicating active killing), and CD8+ PD-1+ cells. PD-L1 expression also increased in the tumor microenvironment.\n\nCritically, the same peptide-specific T-cell receptor sequences were found in both blood and tumor tissue after vaccination, confirming that the vaccine-induced killer T-cells actually infiltrated the tumors. The upregulation of PD-1 and PD-L1 after vaccination suggests that combining S-588410 with checkpoint inhibitors (anti-PD-1/PD-L1 antibodies) could further enhance its anti-cancer effect.","whyItMatters":"Cancer peptide vaccines have long been pursued as a way to train the immune system to specifically target cancer cells. This study provides direct evidence that a peptide vaccine can successfully drive tumor-infiltrating lymphocytes into esophageal tumors — and reveals that the resulting immune response upregulates PD-1/PD-L1, providing a biological rationale for combining peptide vaccines with immune checkpoint inhibitors. This combination strategy could make both therapies more effective.","specificNumbers":"n=15 patients · 5-peptide vaccine · Median 5 doses · CTL response in 100% for ≥1 peptide · 80% had treatment-related AEs · Injection site reactions: grade 1 (n=1), grade 2 (n=11)","methodology":"This was an exploratory open-label clinical study in 15 HLA-A*24:02-positive esophageal cancer patients. S-588410 was administered subcutaneously emulsified with MONTANIDE ISA51VG adjuvant (median 5 doses). Researchers analyzed pre- and post-vaccination tumor tissue for immune cell densities (CD8+, granzyme B+, PD-1+, PD-L1+) using immunohistochemistry. CTL responses were assessed in blood, and peptide-specific T-cell receptor sequencing was performed on both tumor tissue and blood samples.","limitations":"This is an open-label exploratory study with only 15 patients and no control group, making it impossible to attribute clinical benefit to the vaccine. The study focused on immunological endpoints rather than tumor response or survival. Only HLA-A*24:02-positive patients were eligible, limiting applicability. The MONTANIDE adjuvant may contribute to the high rate of injection site reactions."},{"rthcId":"RPEP-04752","title":"Modifying Cell Membranes with Anionic Polymer Amphiphiles Potentiates Intracellular Delivery of Cationic Peptides.","authors":"Dailing, Eric A; Kilchrist, Kameron V; Tierney, J William; Fletcher, R Brock; Evans, Brian C; Duvall, Craig L","year":2020,"journal":"ACS applied materials & interfaces, 12(45), 50222-50235","doi":"10.1021/acsami.0c13304","pmid":"33124813","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04753","title":"Eczema Herpeticum: Clinical and Pathophysiological Aspects.","authors":"Damour, Alexia; Garcia, Magali; Seneschal, Julien; Lévêque, Nicolas; Bodet, Charles","year":2020,"journal":"Clinical reviews in allergy & immunology, 59(1), 1-18","doi":"10.1007/s12016-019-08768-3","pmid":"31836943","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04754","title":"An Update on Pharmaceutical Strategies for Oral Delivery of Therapeutic Peptides and Proteins in Adults and Pediatrics.","authors":"Dan, Nirnoy; Samanta, Kamalika; Almoazen, Hassan","year":2020,"journal":"Children (Basel, Switzerland), 7(12)","doi":"10.3390/children7120307","pmid":"33352795","tags":["oral-peptide-delivery","drug-delivery"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"This review catalogs the major barriers peptide and protein drugs face when taken orally — mucus, digestive enzymes, and the intestinal cell lining — and the pharmaceutical strategies being used to overcome them. Key approaches include: co-administration with protease inhibitors to prevent enzymatic breakdown, PEGylation and mucoadhesive polymers to extend gut residence time, cell-penetrating peptides to cross the intestinal barrier, nanoparticle carriers (liposomes, microspheres, nanospheres) for protected transport, and enteric coatings to survive stomach acid. The review also covers formulations that have reached clinical approval.","whyItMatters":"Most peptide drugs currently require injection because the digestive system destroys them before they can be absorbed. Converting injectable peptide therapies to oral pills would make them far more accessible, especially for children and patients who need daily dosing. This review maps the entire landscape of strategies being used to solve this problem, from established techniques to emerging approaches.","specificNumbers":"","methodology":"This is a narrative review paper synthesizing published research on pharmaceutical strategies for oral delivery of therapeutic peptides and proteins. The authors review the biological barriers in the GI tract, the modification strategies used to enhance oral bioavailability, and clinically approved oral peptide formulations.","limitations":"As a review, this paper synthesizes existing knowledge but doesn't present new experimental data. The field moves quickly, so some strategies discussed may have progressed or been abandoned since publication. The pediatric perspective, while highlighted in the title, may be less extensively covered than adult applications given the smaller body of pediatric peptide research."},{"rthcId":"RPEP-04755","title":"Solution Conformations Explain the Chameleonic Behaviour of Macrocyclic Drugs.","authors":"Danelius, Emma; Poongavanam, Vasanthanathan; Peintner, Stefan; Wieske, Lianne H E; Erdélyi, Máté; Kihlberg, Jan","year":2020,"journal":"Chemistry (Weinheim an der Bergstrasse, Germany), 26(23), 5231-5244","doi":"10.1002/chem.201905599","pmid":"32027758","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04756","title":"Spotlight on the Selected New Antimicrobial Innate Immune Peptides Discovered During 2015-2019.","authors":"Dang, Xiangli; Wang, Guangshun","year":2020,"journal":"Current topics in medicinal chemistry, 20(32), 2984-2998","doi":"10.2174/1568026620666201022143625","pmid":"33092508","tags":["antimicrobial-peptides"],"studyType":"review","evidenceStrength":"review","keyFinding":"Between 2015 and 2019, approximately 500 new natural antimicrobial peptides (AMPs) were discovered and registered in the antimicrobial peptide database. This review highlights the most notable discoveries, including: teixobactin (a cell-wall-inhibiting peptide antibiotic), darobactin (which targets outer membrane protein assembly in Gram-negative bacteria), cOB1 (a sex pheromone from gut bacteria that kills multidrug-resistant E. faecalis at picomolar concentrations), urumin (a frog peptide that specifically inhibits H1 influenza A virus), and TLN-58 (a newly discovered alternative human cathelicidin peptide that proves one gene can produce multiple antimicrobial peptides).\n\nThe review also highlights the expanding functional roles of AMPs beyond infection-fighting — including a fly peptide called nemuri that induces sleep, linking immune defense to sleep regulation.","whyItMatters":"Antibiotic resistance is one of the biggest threats to global health, and new antimicrobial strategies are urgently needed. Natural antimicrobial peptides represent a vast, largely untapped reservoir of potential new drugs. The diversity of sources (bacteria, plants, shrimp, frogs, rats, flies, humans) and mechanisms of action highlighted in this review suggests that nature has already engineered solutions to drug-resistant infections — we just need to find and develop them.","specificNumbers":"~500 new AMPs discovered 2015–2019 · cOB1 active at picomolar concentration · Urumin targets H1 influenza A · TLN-58 is a new human cathelicidin · Rat rattusin forms 5 intermolecular disulfide bonds","methodology":"Narrative review highlighting selected notable antimicrobial peptide discoveries from 2015–2019, drawn from the antimicrobial peptide database. The review covers peptides from diverse organisms including bacteria, plants, shrimp, amphibians, rodents, insects, and humans.","limitations":"As a selective review, this paper highlights noteworthy discoveries rather than providing a comprehensive or systematic analysis of all 500 new AMPs. Most of the highlighted peptides are at the early discovery stage — their therapeutic potential in humans remains largely untested. The translation from laboratory antimicrobial activity to clinical drug development faces many hurdles."},{"rthcId":"RPEP-04757","title":"Invited review. Series: Implications of the recent CVOTs in type 2 diabetes: Which patients for GLP-1RA or SGLT-2 inhibitor?","authors":"Dardano, Angela; Miccoli, Roberto; Bianchi, Cristina; Daniele, Giuseppe; Del Prato, Stefano","year":2020,"journal":"Diabetes research and clinical practice, 162, 108112","doi":"10.1016/j.diabres.2020.108112","pmid":"32198123","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04758","title":"Activatable cell-penetrating peptides: 15 years of research.","authors":"de Jong, Heleen; Bonger, Kimberly M; Löwik, Dennis W P M","year":2020,"journal":"RSC chemical biology, 1(4), 192-203","doi":"10.1039/d0cb00114g","pmid":"34458758","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Since the first activatable cell-penetrating peptide was reported in 2004, multiple activation strategies have been developed to control when and where CPPs become active. These include enzyme-triggered activation (using proteases overexpressed in diseased tissue), pH-responsive activation, light-triggered activation, and other environmental triggers. The review provides a comprehensive overview of these strategies, noting that while significant progress has been made, challenges remain in achieving the specificity and efficiency needed for clinical translation.","whyItMatters":"One of the biggest challenges in drug delivery is getting therapeutics inside the right cells without affecting healthy tissue. Cell-penetrating peptides can solve the membrane crossing problem, but their lack of selectivity has held back clinical applications. ACPPs address this fundamental limitation by adding an 'on/off switch' that activates only under disease-specific conditions. This could be transformative for targeted cancer therapy, gene therapy, and delivery of biologics that cannot cross cell membranes on their own.","specificNumbers":"","methodology":"This is a narrative review article that surveys the published literature on activatable cell-penetrating peptides from 2004 to 2020. The authors categorize and compare the different ACPP strategies, discussing the mechanisms, experimental evidence, advantages, and limitations of each approach.","limitations":"As a review article, this paper synthesizes existing research rather than presenting new experimental data. The abstract does not detail specific quantitative comparisons between ACPP strategies. The review covers literature through 2020, so developments in the past several years are not included. Many of the ACPP strategies reviewed remain in early preclinical stages."},{"rthcId":"RPEP-04759","title":"In silico strategy for detailing the binding modes of a novel family of peptides proven as ghrelin receptor agonists.","authors":"de la Nuez Veulens, Ania; Rodríguez Fernández, Rolando E; Álvarez Ginarte, Yoanna M; Montero Cabrera, Luis A","year":2020,"journal":"Journal of molecular modeling, 26(11), 294","doi":"10.1007/s00894-020-04553-8","pmid":"33015729","tags":["ghrelin","computational"],"studyType":"computational-study","evidenceStrength":"low","keyFinding":"Using computer simulations, researchers mapped how novel cyclic peptide ghrelin analogs (A228 and A233) bind to the ghrelin receptor (GHS-R1a). Despite having different structures from natural ghrelin and GHRP-6, all four peptides share a common binding mode: their N-terminal end interacts with a specific amino acid (E124) on the receptor, and a nearby aromatic residue docks into an aromatic cluster (F279, F309, F312).\n\nFrom this analysis, they proposed a preliminary pharmacophore model — the minimum molecular features needed for ghrelin receptor activation: a positively charged amine and an aromatic ring separated by approximately 0.79 nm. This pharmacophore could serve as a template for designing new ghrelin receptor drugs.\n\nMolecular dynamics simulations over 100 nanoseconds confirmed the stability of these peptide-receptor complexes in a realistic cell membrane environment.","whyItMatters":"Understanding exactly how peptides bind to the ghrelin receptor at the atomic level is essential for designing better growth hormone secretagogues and appetite-regulating drugs. By identifying the minimal structural features required for binding (the pharmacophore), this study provides a blueprint that could accelerate the discovery of new ghrelin analogs with improved potency, selectivity, or oral bioavailability.","specificNumbers":"100 ns molecular dynamics simulation · 0.79 nm optimal distance between pharmacophore features · Key interactions: E124 + aromatic cluster (F279, F309, F312) · 2 novel cyclic peptides analyzed (A228, A233)","methodology":"Computational study using homology modeling to build a 3D structure of the ghrelin receptor (GHS-R1a) from related GPCR crystal structures. Molecular docking predicted peptide orientations in the binding site. Molecular dynamics simulations (100 ns, CHARMM36 force field) in a POPC membrane environment tested complex stability. Results for novel peptides A228 and A233 were compared with ghrelin and GHRP-6.","limitations":"Entirely computational — no experimental validation of the proposed binding modes or pharmacophore model. The ghrelin receptor model is based on homology modeling from other GPCRs, introducing structural uncertainty. The 100 ns simulation timescale may not capture slower conformational changes. The pharmacophore model is preliminary and needs experimental testing."},{"rthcId":"RPEP-04760","title":"Early life stress and the programming of eating behavior and anxiety: Sex-specific relationships with serotonergic activity and hypothalamic neuropeptides.","authors":"de Lima, Randriely Merscher Sobreira; Dos Santos Bento, Lucas Victor; di Marcello Valladão Lugon, Marcelo; Barauna, Valerio Garrone; Bittencourt, Athelson Stefanon; Dalmaz, Carla; de Vasconcellos Bittencourt, Ana Paula Santana","year":2020,"journal":"Behavioural brain research, 379, 112399","doi":"10.1016/j.bbr.2019.112399","pmid":"31790781","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04761","title":"Targeting CGRP for migraine treatment: mechanisms, antibodies, small molecules, perspectives.","authors":"De Matteis, Eleonora; Guglielmetti, Martina; Ornello, Raffaele; Spuntarelli, Valerio; Martelletti, Paolo; Sacco, Simona","year":2020,"journal":"Expert review of neurotherapeutics, 20(6), 627-641","doi":"10.1080/14737175.2020.1772758","pmid":"32434430","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04762","title":"Neoantigen prediction and computational perspectives towards clinical benefit: recommendations from the ESMO Precision Medicine Working Group.","authors":"De Mattos-Arruda, L; Vazquez, M; Finotello, F; Lepore, R; Porta, E; Hundal, J; Amengual-Rigo, P; Ng, C K Y; Valencia, A; Carrillo, J; Chan, T A; Guallar, V; McGranahan, N; Blanco, J; Griffith, M","year":2020,"journal":"Annals of oncology : official journal of the European Society for Medical Oncology, 31(8), 978-990","doi":"10.1016/j.annonc.2020.05.008","pmid":"32610166","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04763","title":"Lactoferrin and lactoferricin B reduce adhesion and biofilm formation in the intestinal symbionts Bacteroides fragilis and Bacteroides thetaiotaomicron.","authors":"de Sá Almeida, Juliana Soares; de Oliveira Marre, Andressa Temperine; Teixeira, Felipe Lopes; Boente, Renata Ferreira; Domingues, Regina M C P; de Paula, Geraldo Renato; Lobo, Leandro A","year":2020,"journal":"Anaerobe, 64, 102232","doi":"10.1016/j.anaerobe.2020.102232","pmid":"32634470","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04764","title":"Functional Impact of BeKm-1, a High-Affinity hERG Blocker, on Cardiomyocytes Derived from Human-Induced Pluripotent Stem Cells.","authors":"De Waard, Stephan; Montnach, Jérôme; Ribeiro, Barbara; Nicolas, Sébastien; Forest, Virginie; Charpentier, Flavien; Mangoni, Matteo Elia; Gaborit, Nathalie; Ronjat, Michel; Loussouarn, Gildas; Lemarchand, Patricia; De Waard, Michel","year":2020,"journal":"International journal of molecular sciences, 21(19)","doi":"10.3390/ijms21197167","pmid":"32998413","tags":[],"studyType":"laboratory","evidenceStrength":"low","keyFinding":"BeKm-1, a scorpion venom peptide that selectively blocks hERG potassium channels from the outside of the cell, successfully reproduced key features of drug-induced long QT syndrome in human stem cell-derived cardiomyocytes. The peptide delayed heart cell repolarization, induced early afterdepolarizations (abnormal electrical events), and reduced spontaneous beating rate, calcium transients, and contraction frequency — all hallmarks of arrhythmia risk.\n\nBecause BeKm-1 blocks hERG from the extracellular face (unlike most drugs that block from inside), it serves as a unique reference compound for cardiac safety testing and as a modifiable molecular platform for designing new hERG-targeting therapeutics.","whyItMatters":"Many drugs are withdrawn from market because they accidentally block hERG channels and cause fatal heart rhythm disorders. This study validates a scorpion venom peptide as a tool for testing cardiac drug safety in human stem cell-derived heart cells, and establishes it as a starting point for engineering new hERG modulators with therapeutic potential.","specificNumbers":"BeKm-1 high-affinity hERG blocker · hiPS-CMs model · Induced early afterdepolarizations · Reduced beating frequency · External face binding (unique mechanism)","methodology":"Laboratory study using human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs). BeKm-1 affinity for hERG channels was compared to reference compounds using automated patch-clamp electrophysiology. Comprehensive assessment included action potential properties, calcium handling, and beating/contraction measurements.","limitations":"This is an in vitro study using stem cell-derived cardiomyocytes, which may not fully replicate mature human heart cell physiology. hiPS-CMs are known to have immature electrophysiological properties. The study does not assess in vivo safety or therapeutic applications of BeKm-1 or its derivatives."},{"rthcId":"RPEP-04765","title":"Changes in the Homeostatic Appetite System After Weight Loss Reflect a Normalization Toward a Lower Body Weight.","authors":"DeBenedictis, Julia Nicole; Nymo, Siren; Ollestad, Karoline Haagensli; Boyesen, Guro Akersveen; Rehfeld, Jens Frederik; Holst, Jens Juul; Truby, Helen; Kulseng, Bard; Martins, Catia","year":2020,"journal":"The Journal of clinical endocrinology and metabolism, 105(7), e2538-46","doi":"10.1210/clinem/dgaa202","pmid":"32301981","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"After 17% body weight loss maintained at one year, reduced-obese adults showed increased hunger ratings and higher ghrelin secretion (both basal and postprandial) compared to their pre-weight-loss baseline. However, these appetite markers were not different from those of body-composition-matched nonobese controls, indicating normalization rather than compensatory overshoot.\n\nPostprandial concentrations of active GLP-1, total peptide YY, and cholecystokinin remained lower in individuals with obesity at all time points compared to nonobese controls — both before and after weight loss. This suggests that blunted satiety peptide secretion is a feature of obesity itself rather than a consequence of weight loss.","whyItMatters":"This study challenges the prevailing narrative that weight loss triggers a permanent state of excessive hunger driven by hormonal changes. Instead, the data suggest that increased appetite after weight loss is simply the body recalibrating to match its new, lower weight — the same appetite levels that lean people naturally have. This is reassuring for weight loss maintenance and has implications for understanding why peptide-based appetite drugs like GLP-1 agonists are effective.","specificNumbers":"","methodology":"This controlled study enrolled 34 adults with obesity who underwent a dietary weight loss program, achieving 17% weight loss at week 13 and maintaining it at one year. They were compared to 33 nonobese controls matched for body composition. All participants underwent standardized meal tests with measurements of subjective appetite ratings and blood concentrations of multiple appetite-related peptide hormones: ghrelin, total PYY, PYY3-36, total and active GLP-1, and cholecystokinin. The weight-loss group was measured at baseline, week 13, and one year.","limitations":"The sample size of 67 participants is moderate and may not capture the full range of individual variation in appetite hormone responses. The study measured peptide concentrations but did not assess receptor sensitivity, which could also change with weight loss. The one-year follow-up, while longer than many weight loss studies, may not capture very long-term hormonal adaptations. The control matching was based on body composition rather than randomization, which could introduce confounding variables."},{"rthcId":"RPEP-04766","title":"A registered replication study on oxytocin and trust.","authors":"Declerck, Carolyn H; Boone, Christophe; Pauwels, Loren; Vogt, Bodo; Fehr, Ernst","year":2020,"journal":"Nature human behaviour, 4(6), 646-655","doi":"10.1038/s41562-020-0878-x","pmid":"32514040","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04767","title":"Impact of ketosis on appetite regulation-a review.","authors":"Deemer, Sarah E; Plaisance, Eric P; Martins, Catia","year":2020,"journal":"Nutrition research (New York, N.Y.), 77, 1-11","doi":"10.1016/j.nutres.2020.02.010","pmid":"32193016","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Ketogenic diets prevent the increase in ghrelin secretion that normally accompanies weight loss, while also reducing hunger and preventing hunger increases. The exact threshold of ketosis required for appetite suppression has not been established.\n\nExogenous ketone esters showed concentration-dependent effects on food intake and body weight in rodent models, with a threshold effect appearing when ketone esters provided 30% of total dietary energy. In a human study, acute consumption of a ketone ester drink reduced feelings of hunger and increased satiety compared to a dextrose (sugar) drink. The mechanisms mediating ketosis-induced appetite suppression remain to be fully elucidated.","whyItMatters":"Weight regain after dieting is the biggest unsolved problem in obesity treatment. The ghrelin rebound — the body's compensatory hunger increase after weight loss — is a major driver. If ketosis can prevent this peptide hormone surge, it could be the key to sustaining weight loss. Understanding the mechanism could lead to targeted interventions (dietary or supplemental) that suppress appetite without relying solely on willpower.","specificNumbers":"","methodology":"Narrative review of published literature on ketosis and appetite regulation, covering evidence from ketogenic diet studies, exogenous ketone ester studies (animal and human), ghrelin and appetite hormone measurements, and proposed mechanisms of action.","limitations":"The exact level of ketosis needed for appetite suppression is unknown. Most evidence for ghrelin suppression comes from short-term studies — long-term effects are unclear. Ketogenic diets have notoriously poor adherence, limiting their practical utility. Human data on exogenous ketone esters and appetite is limited to acute studies. The review acknowledges that underlying mechanisms are not fully understood."},{"rthcId":"RPEP-04768","title":"Liraglutide reduces hyperglycaemia and body weight in overweight, dysregulated insulin-pump-treated patients with type 1 diabetes: The Lira Pump trial-a randomized, double-blinded, placebo-controlled trial.","authors":"Dejgaard, Thomas F; Schmidt, Signe; Frandsen, Christian S; Vistisen, Dorte; Madsbad, Sten; Andersen, Henrik U; Nørgaard, Kirsten","year":2020,"journal":"Diabetes, obesity & metabolism, 22(4), 492-500","doi":"10.1111/dom.13911","pmid":"31696598","tags":["glp-1-agonists"],"studyType":"rct","evidenceStrength":"strong","keyFinding":"Adding liraglutide 1.8 mg daily to insulin pump therapy in overweight adults with type 1 diabetes produced three significant benefits over 26 weeks compared to placebo: HbA1c dropped by 0.5% (vs. a 0.2% increase with placebo, p<0.001), body weight decreased by 6.3 kg (p<0.001), and total insulin dose fell by 8 units/day (16% reduction, p=0.008). Time in the target glucose range (71-180 mg/dL) increased without raising the risk of hypoglycemia.","whyItMatters":"GLP-1 drugs are primarily used for type 2 diabetes and obesity, but some type 1 diabetes patients — especially those who are overweight with poor glucose control — may also benefit. This trial provides rigorous evidence that liraglutide can improve multiple outcomes simultaneously in these patients without the feared increase in dangerous low blood sugar episodes.","specificNumbers":"HbA1c: -0.5% vs. +0.2% (p<0.001) · Weight: -6.3 kg vs. placebo (p<0.001) · Insulin: -8 units/day (-16%, p=0.008) · No increased hypoglycemia","methodology":"26-week randomized, double-blind, placebo-controlled trial (Lira Pump trial). 44 overweight/obese adults with type 1 diabetes on insulin pump therapy (CSII) were randomized 1:1 to liraglutide 1.8 mg once daily or placebo. Primary endpoint was HbA1c change. Secondary endpoints included insulin dose, glycemic variability, body weight, and adverse events.","limitations":"Small sample size (44 patients total, 22 per group). Single-center trial. 26-week duration doesn't capture long-term outcomes or sustainability. Only studied the 1.8 mg dose. Results apply specifically to overweight/obese type 1 patients on insulin pumps — may not generalize to all type 1 diabetes patients. Liraglutide is not FDA-approved for type 1 diabetes."},{"rthcId":"RPEP-04769","title":"Efficacy and safety of calcitonin-gene-related peptide binding monoclonal antibodies for the preventive treatment of episodic migraine - an updated systematic review and meta-analysis.","authors":"Deng, Hong; Li, Gai-Gai; Nie, Hao; Feng, Yang-Yang; Guo, Guang-Yu; Guo, Wen-Liang; Tang, Zhou-Ping","year":2020,"journal":"BMC neurology, 20(1), 57","doi":"10.1186/s12883-020-01633-3","pmid":"32061264","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 11 high-quality RCTs (n=4,402), compared to placebo:\n\n- Monthly migraine days reduced by 1.44 days (WMD: -1.44; 95% CI: -1.68 to -1.19)\n- Acute migraine-specific medication days reduced by 1.28 days (WMD: -1.28; 95% CI: -1.66 to -0.90)\n- 50% responder rate improved by 51% (RR: 1.51; 95% CI: 1.37 to 1.66)\n- Adverse events and withdrawal rates due to AEs were not significantly different from placebo\n- Subgroup analysis showed similar efficacy and safety for erenumab, fremanezumab, and galcanezumab individually","whyItMatters":"This meta-analysis provides high-level evidence confirming that blocking the CGRP peptide pathway is an effective migraine prevention strategy. For the millions of people whose migraines don't respond well to conventional preventive drugs, anti-CGRP antibodies represent a targeted, evidence-based alternative with a favorable safety profile.","specificNumbers":"","methodology":"A systematic review and meta-analysis of 11 randomized controlled trials identified through electronic database searches. Two independent authors extracted data and assessed quality. Mean differences were calculated for continuous outcomes and risk ratios for dichotomous outcomes. Subgroup analyses were performed for each individual anti-CGRP antibody.","limitations":"The follow-up periods in most included trials were relatively short (typically 3–6 months), so long-term efficacy and safety data are limited. The studies focused on episodic migraine, so results may not apply to chronic migraine. The pooled reduction of ~1.4 migraine days per month is statistically significant but may seem modest at an individual level, though the 50% responder rate provides a more clinically meaningful measure."},{"rthcId":"RPEP-04770","title":"A pipeline for identification and validation of tumor-specific antigens in a mouse model of metastatic breast cancer.","authors":"DeVette, Christa I; Gundlapalli, Harika; Lai, Shu-Chin Alicia; McMurtrey, Curtis P; Hoover, Ashley R; Gurung, Hem R; Chen, Wei R; Welm, Alana L; Hildebrand, William H","year":2020,"journal":"Oncoimmunology, 9(1), 1685300","doi":"10.1080/2162402X.2019.1685300","pmid":"32002300","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The research team deployed their NetH2pan prediction tool combined with advanced proteomics to identify five unique MHC class I/PyMT peptide epitopes in the MMTV-PyMT transgenic breast cancer model. These tumor-specific peptides were confirmed to be naturally presented on the surface of primary tumors by MHC class I molecules.\n\nT cell immunogenicity of all five epitopes was validated — meaning the immune system could recognize and respond to these peptides. A DNA vaccine encoding a truncated PyMT protein generated CD8+ T cell responses targeting these specific MHC class I/peptide complexes and prevented tumor development in the metastatic breast cancer model.","whyItMatters":"Breast cancer remains a leading cause of cancer death, and metastatic breast cancer has been particularly resistant to immunotherapy compared to cancers like melanoma. A major barrier has been identifying which peptide targets the immune system should attack. This study establishes a complete pipeline — from prediction to validation to vaccination — that could be adapted for human breast cancer and other tumor types, potentially enabling personalized cancer vaccines.","specificNumbers":"","methodology":"The researchers first built an MHC ligand prediction tool (NetH2pan) for the FVB/NJ mouse strain by creating an H-2q ligand database combined with data from six other murine MHC alleles. They then used this tool alongside advanced proteomics (mass spectrometry) to identify peptides presented on tumor cell surfaces. Candidate peptides were validated for T cell immunogenicity. A DNA construct encoding truncated PyMT protein was used as a vaccine, and tumor prevention was assessed in MMTV-PyMT transgenic mice.","limitations":"All experiments were conducted in mice using a transgenic breast cancer model. The MMTV-PyMT model, while well-established for studying breast cancer biology, uses a viral oncogene (PyMT) that doesn't exist in human breast cancer — so the specific peptide targets identified here are not directly applicable to human patients. The vaccine was tested preventively (before tumor development), and whether it would work against established tumors is unknown. Translation to human breast cancer would require identifying human-relevant neoantigens using the same pipeline approach."},{"rthcId":"RPEP-04771","title":"Emerging insights into mitochondria-specific targeting and drug delivering strategies: Recent milestones and therapeutic implications.","authors":"Dhanasekaran, Sugapriya; Venugopal, Divya; Al-Dayan, Noura; Ravinayagam, Vijaya; Mohammed, Arif Ahmed","year":2020,"journal":"Saudi journal of biological sciences, 27(12), 3581-3592","doi":"10.1016/j.sjbs.2020.07.030","pmid":"33304169","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies three primary peptide-based and molecular strategies for mitochondria-specific drug delivery:\n\n1. Mitochondrial targeting signal peptides (MTS): Short peptide sequences that exploit the cell's natural protein import machinery to deliver therapeutic cargo directly into mitochondria.\n\n2. Cell-penetrating peptides (CPPs): Peptides that can cross cell membranes and carry attached drug molecules into cells and their organelles, including mitochondria.\n\n3. Lipophilic cations: Positively charged molecules that accumulate in mitochondria driven by the mitochondrial membrane potential.\n\nThe review notes that conjugating these targeting ligands to therapeutic molecules enhances their effectiveness, and that nanoparticle-based delivery systems can address remaining challenges related to drug solubility and selectivity.","whyItMatters":"Most anticancer drugs work throughout the entire cell, causing collateral damage that leads to side effects. By delivering drugs precisely to mitochondria — where key decisions about cell death are made — therapies could be both more effective and less toxic. Peptide-based targeting is particularly promising because peptides can be rationally designed and easily conjugated to drug molecules, creating precise molecular delivery vehicles.","specificNumbers":"","methodology":"This is a narrative review article summarizing the published literature on mitochondria-specific drug targeting strategies. It covers molecular mechanisms, ligand design, conjugation strategies, and nanocarrier delivery systems for mitochondria-targeted anticancer therapies.","limitations":"As a narrative review, this paper summarizes existing literature rather than presenting new experimental data. The review was published in 2020 and may not reflect the most recent advances in the rapidly evolving field of targeted drug delivery. Most strategies discussed are in preclinical stages, with limited clinical translation data. The review focuses primarily on cancer applications and does not extensively cover other diseases involving mitochondrial dysfunction."},{"rthcId":"RPEP-04772","title":"The Lacritin-Syndecan-1-Heparanase Axis in Dry Eye Disease.","authors":"Dias-Teixeira, Karina; Horton, Xavier; McKown, Robert; Romano, Jeffrey; Laurie, Gordon W","year":2020,"journal":"Advances in experimental medicine and biology, 1221, 747-757","doi":"10.1007/978-3-030-34521-1_31","pmid":"32274735","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04773","title":"Defensin-driven viral evolution.","authors":"Diaz, Karina; Hu, Ciara T; Sul, Youngmee; Bromme, Beth A; Myers, Nicolle D; Skorohodova, Ksenia V; Gounder, Anshu P; Smith, Jason G","year":2020,"journal":"PLoS pathogens, 16(11), e1009018","doi":"10.1371/journal.ppat.1009018","pmid":"33232373","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"When a defensin-sensitive adenovirus serotype was passaged in the presence of human defensin, mutations accumulated in the hexon protein — the major capsid protein — rather than in the vertex proteins previously identified as important for defensin antiviral activity.\n\nInfection and biochemical assays revealed that defensins interact with all major capsid proteins, creating a balance between two opposing effects: increased cell binding (which could enhance infection) and a downstream block in intracellular trafficking (which inhibits infection). The net outcome of infection depends on which effect dominates. This demonstrates that defensins impose genuine selective pressure during fecal-oral transmission, driving viral evolution and explaining why closely related viruses can have very different infection outcomes.","whyItMatters":"This study reveals that the antimicrobial peptides in your gut don't just kill pathogens — they shape how viruses evolve. This is a new dimension of the evolutionary arms race between hosts and pathogens. Understanding how defensins drive viral evolution could explain why certain virus strains are more infectious than others and could inform the development of antiviral strategies that are harder for viruses to evolve resistance against.","specificNumbers":"","methodology":"Laboratory evolution experiment. Researchers passaged a defensin-sensitive adenovirus serotype in the presence of a human enteric alpha-defensin over multiple generations and sequenced the resulting viral genomes to identify adaptive mutations. They then used infection assays and biochemical analyses to characterize how the mutations affected defensin-virus interactions, cell binding, and intracellular trafficking in A549 cells.","limitations":"The study was conducted in vitro with a single adenovirus serotype and one human defensin — the findings may not generalize to all virus-defensin interactions. Laboratory evolution under controlled conditions may not fully replicate the complex selective pressures during natural fecal-oral transmission. The mechanism was studied in A549 lung cancer cells, not intestinal epithelial cells where defensins naturally act. The balance between cell binding enhancement and trafficking block may differ across cell types."},{"rthcId":"RPEP-04774","title":"Liraglutide as Adjunct to Insulin Treatment in Patients with Type 1 Diabetes: A Systematic Review and Meta-analysis.","authors":"Dimitrios, Patoulias; Michael, Doumas; Vasilios, Kotsis; Konstantinos, Stavropoulos; Konstantinos, Imprialos; Ioanna, Zografou; Konstantinos, Petidis; Spyridon, Bakatselos; Asterios, Karagiannis","year":2020,"journal":"Current diabetes reviews, 16(4), 313-326","doi":"10.2174/1573399815666190614141918","pmid":"31203802","tags":[],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Across 5 RCTs with 2,445 participants, liraglutide added to insulin in type 1 diabetes produced modest HbA1c reductions (up to -0.24% with 1.8 mg dose), significant weight loss (up to 4.87 kg), and decreased total daily insulin requirements — mainly bolus insulin.\n\nSevere hypoglycemia was non-significantly reduced (OR=0.80), but gastrointestinal side effects increased substantially: nausea odds were 4.7 times higher and vomiting 2.5 times higher. Heart rate also increased. No link to diabetic ketoacidosis or malignancies was found.","whyItMatters":"Type 1 diabetes treatment has relied almost exclusively on insulin, with limited options for adjunct therapy. GLP-1 agonists like liraglutide are widely used in type 2 diabetes but their role in type 1 is less established. This meta-analysis provides the most comprehensive evidence to date that liraglutide can meaningfully reduce weight and insulin requirements in T1D patients, though the blood sugar benefit is modest and GI side effects are significant.","specificNumbers":"n=2,445 across 5 RCTs · HbA1c: -0.24% (1.8 mg) · Weight loss: -4.87 kg (1.8 mg) · Nausea OR=4.70 · Vomiting OR=2.50 · Severe hypoglycemia OR=0.80 (NS)","methodology":"Systematic review and meta-analysis of 5 randomized controlled trials (≥12 weeks duration) comparing liraglutide vs placebo as add-on to insulin in type 1 diabetes patients. Searched major databases and grey literature through October 2018. Reported per PRISMA guidelines. Assessed efficacy (HbA1c, weight, insulin dose) and safety (hypoglycemia, GI events, ketoacidosis) endpoints.","limitations":"Only 5 trials met inclusion criteria, limiting the ability to detect rarer adverse events. Follow-up durations were relatively short (≥12 weeks), so long-term safety and efficacy in T1D remain uncertain. The modest HbA1c reduction (-0.24%) may not justify the high rate of GI side effects for all patients. Individual patient factors that predict who benefits most were not explored."},{"rthcId":"RPEP-04775","title":"Evidence for neurogenic inflammation in lichen planopilaris and frontal fibrosing alopecia pathogenic mechanism.","authors":"Doche, Isabella; Wilcox, George L; Ericson, Marna; Valente, Neusa S; Romiti, Ricardo; McAdams, Brian D; Hordinsky, Maria K","year":2020,"journal":"Experimental dermatology, 29(3), 282-285","doi":"10.1111/exd.13835","pmid":"30408256","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Immunohistochemistry and confocal microscopy revealed altered expression of substance P and CGRP in both affected and unaffected scalp skin from LPP and FFA patients compared to controls. However, ELISA quantification showed opposite patterns in LPP versus FFA — suggesting different pathogenic mechanisms despite similar histopathological features. Notably, inflammation was present in clinically unaffected scalp skin in both diseases, indicating these may be more generalized scalp processes than previously thought.","whyItMatters":"FFA has reached epidemic levels in recent years with no clear cause identified. If neurogenic inflammation drives these scarring hair loss conditions, it opens the door to targeted treatments — potentially including drugs that block substance P or CGRP (some of which already exist for other conditions like migraines). Understanding the distinct mechanisms of LPP vs FFA is crucial for developing disease-specific therapies.","specificNumbers":"","methodology":"Scalp biopsies from patients with LPP, FFA, and healthy controls were analyzed using immunohistochemistry and confocal microscopy to visualize substance P and CGRP expression. ELISA was used to quantitatively compare neuropeptide levels between affected and unaffected scalp tissue across all three groups.","limitations":"This was a small study with scalp biopsies from a limited number of patients. The abstract does not specify exact sample sizes or the magnitude of neuropeptide differences. The opposite ELISA patterns are suggestive but need replication in larger cohorts. The study cannot determine whether neuropeptide changes cause the disease or are a consequence of it."},{"rthcId":"RPEP-04776","title":"Peptide Isolation via Spray Drying: Particle Formation, Process Design and Implementation for the Production of Spray Dried Glucagon.","authors":"Doerr, Frederik J S; Burns, Lee J; Lee, Becky; Hinds, Jeremy; Davis-Harrison, Rebecca L; Frank, Scott A; Florence, Alastair J","year":2020,"journal":"Pharmaceutical research, 37(12), 255","doi":"10.1007/s11095-020-02942-5","pmid":"33319329","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The spray drying process achieved yields up to 84.67% for trehalose and >83.24% for glucagon and glucagon-trehalose formulations. A psychrometric process model identified optimal operating conditions that significantly reduced residual moisture and particle agglomeration compared to non-optimal drying. Critically, extensive peptide aggregation or fibrillation (a common problem with glucagon) was not observed in the spray-dried product, confirming the process preserved peptide integrity.","whyItMatters":"Peptide drugs like glucagon are notoriously difficult to manufacture because they're fragile and prone to degradation, aggregation, and fibrillation. Most peptide drugs are freeze-dried, which is slow and expensive. If spray drying can reliably produce stable peptide powders at higher throughput, it could reduce manufacturing costs and improve the supply of life-saving peptide medications.","specificNumbers":"","methodology":"Single droplet drying experiments characterized particle formation. Lab-scale spray drying was implemented with in-line process analytical technology (PAT) monitoring temperature, humidity, pressure, and feed rate in a data acquisition framework. Off-line characterization assessed residual moisture, solid state structure, particle size/morphology, and peptide fibrillation/degradation. A psychrometric model guided identification of feasible operating conditions.","limitations":"The study was conducted at lab-scale only; scale-up to commercial manufacturing may introduce additional challenges. Only glucagon was tested, and other peptides with different stability profiles may behave differently. Long-term storage stability of the spray-dried glucagon was not assessed. The study did not compare the bioactivity of spray-dried glucagon to freeze-dried glucagon in biological assays."},{"rthcId":"RPEP-04777","title":"Hyaluronan Degradation by Cemip Regulates Host Defense against Staphylococcus aureus Skin Infection.","authors":"Dokoshi, Tatsuya; Zhang, Ling-Juan; Li, Fengwu; Nakatsuji, Teruaki; Butcher, Anna; Yoshida, Hiroyuki; Shimoda, Masayuki; Okada, Yasunori; Gallo, Richard L","year":2020,"journal":"Cell reports, 30(1), 61-68.e4","doi":"10.1016/j.celrep.2019.12.001","pmid":"31914398","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04778","title":"Thymosin alpha 1: A comprehensive review of the literature.","authors":"Dominari, Asimina; Hathaway Iii, Donald; Pandav, Krunal; Matos, Wanessa; Biswas, Sharmi; Reddy, Gowry; Thevuthasan, Sindhu; Khan, Muhammad Adnan; Mathew, Anoopa; Makkar, Sarabjot Singh; Zaidi, Madiha; Fahem, Michael Maher Mourad; Beas, Renato; Castaneda, Valeria; Paul, Trissa; Halpern, John; Baralt, Diana","year":2020,"journal":"World journal of virology, 9(5), 67-78","doi":"10.5501/wjv.v9.i5.67","pmid":"33362999","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review synthesizes evidence showing thymosin alpha-1 has clinical applications across multiple domains: treatment of immunocompromised states and malignancies, enhancement of vaccine responses, and reduction of morbidity and mortality in sepsis and infections. For COVID-19 specifically, studies suggest thymosin alpha-1 could repair lymphocytic immunity damage while preventing excessive T cell activation — addressing both the immune suppression and hyperactivation that characterize severe COVID-19.","whyItMatters":"Thymosin alpha-1 is one of the best-studied immune-modulating peptides, approved in over 35 countries for various indications. As interest in peptide therapeutics grows, understanding this well-established peptide's broad immune-enhancing properties provides a foundation for both current clinical use and future applications. Its potential to modulate (rather than simply suppress or stimulate) immunity makes it uniquely valuable for complex conditions where immune balance is critical.","specificNumbers":"","methodology":"Comprehensive literature review covering the biochemistry, mechanism of action, and clinical applications of thymosin alpha-1. The review draws from preclinical studies, clinical trials, and emerging COVID-19 research to provide a complete overview of the peptide's therapeutic potential.","limitations":"As a narrative review, this does not include systematic search methodology or meta-analysis. Much of the clinical evidence for thymosin alpha-1 comes from smaller trials, with limited large-scale randomized controlled trials for many indications. The COVID-19 applications were speculative at the time of publication. The review's scope is broad, which limits depth on any single application."},{"rthcId":"RPEP-04779","title":"Amelioration of Compound 48/80-Mediated Itch and LL-37-Induced Inflammation by a Single-Stranded Oligonucleotide.","authors":"Dondalska, Aleksandra; Rönnberg, Elin; Ma, Haisha; Pålsson, Sandra Axberg; Magnusdottir, Elin; Gao, Tianle; Adam, Lucille; Lerner, Ethan A; Nilsson, Gunnar; Lagerström, Malin; Spetz, Anna-Lena","year":2020,"journal":"Frontiers in immunology, 11, 559589","doi":"10.3389/fimmu.2020.559589","pmid":"33101278","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04780","title":"Dual-Modified Liposome for Targeted and Enhanced Gene Delivery into Mice Brain.","authors":"Dos Santos Rodrigues, Bruna; Lakkadwala, Sushant; Kanekiyo, Takahisa; Singh, Jagdish","year":2020,"journal":"The Journal of pharmacology and experimental therapeutics, 374(3), 354-365","doi":"10.1124/jpet.119.264127","pmid":"32561686","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04781","title":"Nanoparticles Functionalized with Venom-Derived Peptides and Toxins for Pharmaceutical Applications.","authors":"Dos Santos, Ana P; de Araújo, Tamara G; Rádis-Baptista, Gandhi","year":2020,"journal":"Current pharmaceutical biotechnology, 21(2), 97-109","doi":"10.2174/1389201020666190621104624","pmid":"31223083","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04782","title":"The potential of GHK as an anti-aging peptide.","authors":"Dou, Yan; Lee, Amanda; Zhu, Lida; Morton, John; Ladiges, Warren","year":2020,"journal":"Aging pathobiology and therapeutics, 2(1), 58-61","doi":"10.31491/apt.2020.03.014","pmid":"35083444","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04783","title":"Injectable combination therapies for the management of diabetes: an Indian perspective.","authors":"Dutta, Deep; Khandelwal, Deepak; Kalra, Sanjay","year":2020,"journal":"Expert opinion on drug metabolism & toxicology, 16(3), 209-216","doi":"10.1080/17425255.2020.1735351","pmid":"32098522","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Nine types of injectable combination therapies (ICTs) are currently available for diabetes, including combinations of conventional human insulin, insulin analogs, insulin coformulations, and insulin/GLP-1 receptor agonist combinations. Meta-analysis data showed no significant differences in HbA1c reduction, hypoglycemia, weight change, or daily insulin dose between ICTs and basal-bolus regimens. ICTs are recommended by all international guidelines for treatment intensification, offering reduced daily needle-prick count and improved long-term compliance.","whyItMatters":"Managing type 2 diabetes often requires multiple daily injections, which creates a significant barrier to treatment adherence — especially in countries like India with enormous diabetes populations. Injectable combination therapies simplify regimens by combining insulin and/or GLP-1 receptor agonists into fewer injections, achieving equivalent glycemic control with better convenience and compliance.","specificNumbers":"","methodology":"Literature review searching PubMed, Medline, and Embase for articles published through July 2019 using MeSH terms and keywords for insulin, GLP-1 analogues, and combination therapy. The review synthesizes evidence from clinical trials, meta-analyses, and international guidelines, with particular focus on the Indian clinical context.","limitations":"The literature search only extends to July 2019, missing more recent combination therapy approvals and trial data. The Indian perspective may not fully generalize to other healthcare systems with different cost structures and drug availability. As a narrative review, the article does not apply systematic review methodology. Specific meta-analysis numbers and forest plots are not detailed in the abstract."},{"rthcId":"RPEP-04784","title":"New insight into the role of substance P/neurokinin-1 receptor system in breast cancer progression and its crosstalk with microRNAs.","authors":"Ebrahimi, Safieh; Javid, Hosein; Alaei, Amin; Hashemy, Seyed Isaac","year":2020,"journal":"Clinical genetics, 98(4), 322-330","doi":"10.1111/cge.13750","pmid":"32266968","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04785","title":"EJP18 peptide derived from the juxtamembrane domain of epidermal growth factor receptor represents a novel membrane-active cell-penetrating peptide.","authors":"Eissa, N G; Sayers, E J; Birch, D; Patel, S G; Tsai, Y-H; Nielsen, H Mørck; Jones, A T","year":2020,"journal":"The Biochemical journal, 477(1), 45-60","doi":"10.1042/BCJ20190452","pmid":"31820794","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04786","title":"Possible role of peptide YY (PYY) in the pathophysiology of irritable bowel syndrome (IBS).","authors":"El-Salhy, Magdy; Hatlebakk, Jan Gunnar; Hausken, Trygve","year":2020,"journal":"Neuropeptides, 79, 101973","doi":"10.1016/j.npep.2019.101973","pmid":"31727345","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review synthesizes several key findings about PYY in IBS:\n\n• PYY concentration and PYY-producing endocrine cell density are decreased in both the colon and rectum of IBS patients\n• PYY cell density in the ileum (small intestine) remains unchanged\n• The reduced PYY cells may result from decreased stem cell differentiation toward endocrine cell lineages\n• PYY regulates intestinal motility, secretion, absorption, and visceral sensitivity by modulating serotonin release\n• PYY abnormalities may therefore contribute to the intestinal dysmotility and visceral hypersensitivity characteristic of IBS\n• A low-FODMAP diet restores PYY cell density in the large intestine and improves abdominal symptoms in IBS patients","whyItMatters":"IBS affects an estimated 10-15% of the global population and has no cure. Understanding that a specific peptide abnormality — reduced PYY cells — may underlie key symptoms offers both a mechanistic explanation and a therapeutic target. The finding that a low-FODMAP diet can restore PYY cell density provides a science-backed rationale for dietary management of IBS and could inform future peptide-based therapies.","specificNumbers":"","methodology":"This is a narrative review synthesizing published research on PYY and its role in IBS pathophysiology. The authors compiled data from studies measuring PYY cell density, PYY concentrations, and the effects of dietary intervention (low-FODMAP diet) on PYY cell populations and IBS symptoms in clinical populations.","limitations":"As a narrative review, this synthesizes existing evidence without generating new data. The causal relationship between PYY deficiency and IBS symptoms is proposed but not definitively proven — the reduced PYY cells could be a consequence rather than a cause of IBS. Most referenced studies likely had relatively small sample sizes. The review doesn't address PYY differences across IBS subtypes (IBS-D, IBS-C, IBS-M) in detail."},{"rthcId":"RPEP-04787","title":"MHC-restricted phosphopeptide antigens: preclinical validation and first-in-humans clinical trial in participants with high-risk melanoma.","authors":"Engelhard, Victor H; Obeng, Rebecca C; Cummings, Kara L; Petroni, Gina R; Ambakhutwala, Angela L; Chianese-Bullock, Kimberly A; Smith, Kelly T; Lulu, Amanda; Varhegyi, Nikole; Smolkin, Mark E; Myers, Paisley; Mahoney, Keira E; Shabanowitz, Jeffrey; Buettner, Nico; Hall, Emily H; Haden, Kathleen; Cobbold, Mark; Hunt, Donald F; Weiss, Geoffrey; Gaughan, Elizabeth; Slingluff, Craig L","year":2020,"journal":"Journal for immunotherapy of cancer, 8(1)","doi":"10.1136/jitc-2019-000262","pmid":"32385144","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04788","title":"The intra-individual stability of GH biomarkers IGF-I and P-III-NP in relation to GHRH administration, menstrual cycle, and hematological parameters.","authors":"Ericsson, Magnus; Bhuiyan, Hasanuzzaman; Yousif, Basam; Lehtihet, Mikael; Ekström, Lena","year":2020,"journal":"Drug testing and analysis, 12(11-12), 1620-1628","doi":"10.1002/dta.2953","pmid":"33125822","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04789","title":"Changes in substance P levels of inferior turbinate in patients with mucosal contact headache.","authors":"Eyigör, Hülya; Eyigör, Mete; Erol, Bekir; Selçuk, Ömer Tarık; Renda, Levent; Yılmaz, Mustafa Deniz; Osma, Üstün; Demirkıran, Cansu; Gültekin, Meral; Erin, Nuray","year":2020,"journal":"Brazilian journal of otorhinolaryngology, 86(4), 450-455","doi":"10.1016/j.bjorl.2019.01.006","pmid":"30846421","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04790","title":"Antimicrobial Peptide-Loaded Nanoparticles as Inhalation Therapy for Pseudomonas aeruginosa Infections.","authors":"Falciani, Chiara; Zevolini, Fabrizia; Brunetti, Jlenia; Riolo, Giulia; Gracia, Raquel; Marradi, Marco; Loinaz, Iraida; Ziemann, Christina; Cossío, Unai; Llop, Jordi; Bracci, Luisa; Pini, Alessandro","year":2020,"journal":"International journal of nanomedicine, 15, 1117-1128","doi":"10.2147/IJN.S218966","pmid":"32110011","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04791","title":"Combinatorial Oxytocin Neuropharmacology in Social Cognition.","authors":"Fan, Siqi; Weinberg-Wolf, Hannah; Piva, Matthew; Dal Monte, Olga; Chang, Steve W C","year":2020,"journal":"Trends in cognitive sciences, 24(1), 8-12","doi":"10.1016/j.tics.2019.10.004","pmid":"31735541","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04792","title":"A C-terminal peptide of TFPI-1 facilitates cytosolic delivery of nucleic acid cargo into mammalian cells.","authors":"Fazil, Mobashar Hussain Urf Turabe; Chalasani, Madhavi Latha Somaraju; Choong, Yeu Khai; Schmidtchen, Artur; Verma, Navin Kumar; Saravanan, Rathi","year":2020,"journal":"Biochimica et biophysica acta. Biomembranes, 1862(2), 183093","doi":"10.1016/j.bbamem.2019.183093","pmid":"31672541","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04793","title":"Prediction of Amphiphilic Cell-Penetrating Peptide Building Blocks from Protein-Derived Amino Acid Sequences for Engineering of Drug Delivery Nanoassemblies.","authors":"Feger, Guillaume; Angelov, Borislav; Angelova, Angelina","year":2020,"journal":"The journal of physical chemistry. B, 124(20), 4069-4078","doi":"10.1021/acs.jpcb.0c01618","pmid":"32337991","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The study presents a computational pipeline combining multiple machine learning methods (SVM, random forest classifiers, and neural networks) to predict amphiphilic cell-penetrating peptide sequences from the human Ki-67 protein. Ki-67 naturally acts as a biosurfactant — a steric and electrostatic barrier against chromosome collapse during cell division — making it a unique source for amphiphilic peptide building blocks. The predicted peptides are designed to spontaneously form self-assembled nanocarriers with enhanced cellular uptake and inherent low immunogenicity.","whyItMatters":"Designing effective drug delivery peptides traditionally requires expensive and time-consuming trial-and-error synthesis. AI-driven prediction could dramatically accelerate this process, screening millions of potential sequences computationally before synthesizing only the best candidates. Deriving CPPs from human proteins (rather than viruses or toxins) adds a safety advantage — reduced immune reactions — that could improve clinical translation.","specificNumbers":"","methodology":"Computational study using an ensemble of web-accessible machine learning predictors to identify amphiphilic CPP sequences from the human Ki-67 protein. The approach combined support vector machine (SVM), random forest (RF), and neural network (NN) classifiers to predict peptide sequences with optimal amphiphilicity, cell-penetrating ability, and self-assembly properties. The design strategy aimed to create peptide building blocks for therapeutic delivery nanoassemblies.","limitations":"This is a computational prediction study — the designed peptides were not synthesized or experimentally validated. Machine learning predictions require experimental confirmation to verify CPP activity, self-assembly, and actual drug delivery capability. The choice of Ki-67 as the source protein, while interesting, is somewhat arbitrary — many human proteins could serve as CPP sources. The computational tools used have known accuracy limitations. Stability, toxicity, and in vivo performance cannot be predicted computationally with current methods."},{"rthcId":"RPEP-04794","title":"Validated mass spectrometric assay for the quantification of substance P and human hemokinin-1 in plasma samples: A design of experiments concept for comprehensive method development.","authors":"Feickert, Martin; Burckhardt, Bjoern B","year":2020,"journal":"Journal of pharmaceutical and biomedical analysis, 191, 113542","doi":"10.1016/j.jpba.2020.113542","pmid":"32871415","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04795","title":"Design, Synthesis, and Characterization of the Macrocyclic Tetrapeptide cyclo[Pro-Sar-Phe-d-Phe]: A Mixed Opioid Receptor Agonist-Antagonist Following Oral Administration.","authors":"Ferracane, Michael J; Brice-Tutt, Ariana C; Coleman, Jeremy S; Simpson, Grant G; Wilson, Lisa L; Eans, Shainnel O; Stacy, Heather M; Murray, Thomas F; McLaughlin, Jay P; Aldrich, Jane V","year":2020,"journal":"ACS chemical neuroscience, 11(9), 1324-1336","doi":"10.1021/acschemneuro.0c00086","pmid":"32251585","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Cyclo[Pro-Sar-Phe-d-Phe] was rationally designed based on X-ray and NMR structures of related macrocyclic tetrapeptides. Key pharmacological findings:\n\n- **Orally bioavailable**: The peptide produced antinociception (pain relief) and kappa opioid receptor (KOR) antagonism when given orally in mice.\n- **Anti-relapse effects**: Oral administration blocked both stress-induced and drug-induced reinstatement of cocaine and morphine conditioned place preference — the gold-standard preclinical model for relapse.\n- **Reduced side effects**: The peptide showed a decreased side-effect profile compared to morphine.\n- **Mixed opioid profile**: It acts as an agonist at some opioid receptors while antagonizing kappa opioid receptors, a profile thought to be ideal for treating addiction.","whyItMatters":"The opioid crisis and cocaine abuse collectively destroy millions of lives, and current treatments for relapse prevention are limited. An orally bioavailable peptide that blocks relapse to multiple drugs of abuse — with fewer side effects than existing opioids — addresses a massive unmet need. The fact that it works against both stress-induced and drug-induced relapse is especially significant, as these are the two main triggers for relapse in humans.","specificNumbers":"","methodology":"The peptide was rationally designed using structural data from related compounds, synthesized, and characterized. Conformational analysis used NMR spectroscopy and molecular modeling, revealing multiple conformations in polar solvents but a single hydrogen-bond-stabilized conformation in chloroform. Pharmacological testing included the mouse 55°C warm-water tail-withdrawal assay (for pain/opioid activity) and conditioned place preference assays (for cocaine and morphine relapse prevention), all via oral administration.","limitations":"All data are from mouse models; oral bioavailability and anti-relapse effects may differ in humans. The specific mechanism of how this peptide prevents relapse (which receptor interactions are most important) was not fully elucidated. Long-term dosing studies and abuse liability assessments were not reported. The conditioned place preference model, while well-established, doesn't fully capture the complexity of human addiction and relapse."},{"rthcId":"RPEP-04796","title":"A Cell-Free SDKP-Conjugated Self-Assembling Peptide Hydrogel Sufficient for Improvement of Myocardial Infarction.","authors":"Firoozi, Saman; Pahlavan, Sara; Ghanian, Mohammad-Hossein; Rabbani, Shahram; Tavakol, Shima; Barekat, Maryam; Yakhkeshi, Saeed; Mahmoudi, Elena; Soleymani, Mansoureh; Baharvand, Hossein","year":2020,"journal":"Biomolecules, 10(2)","doi":"10.3390/biom10020205","pmid":"32019267","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04797","title":"The consequences of exercise-induced weight loss on food reinforcement. A randomized controlled trial.","authors":"Flack, Kyle D; Hays, Harry M; Moreland, Jack","year":2020,"journal":"PloS one, 15(6), e0234692","doi":"10.1371/journal.pone.0234692","pmid":"32555624","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04798","title":"Effects of Exercise during Weight Loss Maintenance on Appetite Regulation in Women.","authors":"Foright, Rebecca; Halliday, Tanya M; Melanson, Edward L; Hild, Allison; Legget, Kristina T; Tregellas, Jason R; Cornier, Marc-Andre","year":2020,"journal":"Translational journal of the American College of Sports Medicine, 5(12)","doi":"10.1249/tjx.0000000000000133","pmid":"33748418","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04799","title":"Assessing the Risk for Gout With Sodium-Glucose Cotransporter-2 Inhibitors in Patients With Type 2 Diabetes: A Population-Based Cohort Study.","authors":"Fralick, Michael; Chen, Sarah K; Patorno, Elisabetta; Kim, Seoyoung C","year":2020,"journal":"Annals of internal medicine, 172(3), 186-194","doi":"10.7326/M19-2610","pmid":"31931526","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04800","title":"Using Data From Routine Care to Estimate the Effectiveness and Potential Limitations of Outcomes-Based Contracts for Diabetes Medications.","authors":"Fralick, Michael; Gagne, Joshua J; Patorno, Elisabetta; Levin, Raisa; Kesselheim, Aaron S","year":2020,"journal":"Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research, 23(4), 434-440","doi":"10.1016/j.jval.2019.11.004","pmid":"32327160","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04801","title":"Peptide-Based Scaffolds for the Culture and Transplantation of Human Dopaminergic Neurons.","authors":"Francis, Nicola L; Zhao, Nanxia; Calvelli, Hannah R; Saini, Astha; Gifford, Janace J; Wagner, George C; Cohen, Rick I; Pang, Zhiping P; Moghe, Prabhas V","year":2020,"journal":"Tissue engineering. Part A, 26(3-4), 193-205","doi":"10.1089/ten.TEA.2019.0094","pmid":"31537172","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Dopaminergic neurons derived from human induced pluripotent stem cells were encapsulated in self-assembling peptide nanofiber scaffolds (SAPNS) based on the peptide RADA16-I. The encapsulated neurons expressed mature neuronal and midbrain dopaminergic markers and showed functional activity comparable to standard 2D cultures.\n\nWhen transplanted into the striatum of 6-OHDA-lesioned Parkinson's disease model mice, SAPNS microspheres significantly increased in vivo neuron survival compared with neurons transplanted in conventional suspension. Critically, the scaffold-transplanted neurons enabled significant motor function recovery using approximately an order of magnitude (roughly 10x) fewer neurons than have been previously required to demonstrate behavioral improvement.","whyItMatters":"Parkinson's disease affects millions of people worldwide, and cell replacement therapy is one of the most promising potential treatments. But the poor survival of transplanted neurons has been a major roadblock. By using peptide-based scaffolds that protect and support neurons during and after transplantation, this approach could make cell therapy far more efficient — needing roughly 10 times fewer donor cells to achieve the same benefit.","specificNumbers":"","methodology":"Researchers used self-assembling peptide nanofiber scaffolds (RADA16-I) to encapsulate human dopaminergic neurons derived from induced pluripotent stem cells. A microfluidic droplet generation method created uniform microspheres containing the neurons. These were transplanted into the striatum of mice with 6-hydroxydopamine-induced Parkinson's-like lesions. Results were compared against neurons transplanted in standard suspension and control lesioned mice, measuring both neuron survival and motor function recovery.","limitations":"This study was conducted in mice, and results from animal models of Parkinson's disease do not always translate to humans. The specific number of animals and statistical details are not provided in the abstract. Long-term survival and function of the transplanted neurons were not discussed. The 6-OHDA lesion model captures only some aspects of human Parkinson's disease pathology."},{"rthcId":"RPEP-04802","title":"Levels of the Novel Endogenous Antagonist of Ghrelin Receptor, Liver-Enriched Antimicrobial Peptide-2, in Patients with Rheumatoid Arthritis.","authors":"Francisco, Vera; Tovar, Sulay; Conde, Javier; Pino, Jesús; Mera, Antonio; Lago, Francisca; González-Gay, Miguel Angel; Dieguez, Carlos; Gualillo, Oreste","year":2020,"journal":"Nutrients, 12(4)","doi":"10.3390/nu12041006","pmid":"32268520","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04803","title":"Development and Validation of an LC-MS-Based Quantification Assay for New Therapeutic Antibodies: Application to a Novel Therapy against Herpes Simplex Virus.","authors":"Fresnais, Margaux; Longuespée, Rémi; Sauter, Max; Schaller, Torsten; Arndt, Michaela; Krauss, Jürgen; Blank, Antje; Haefeli, Walter E; Burhenne, Jürgen","year":2020,"journal":"ACS omega, 5(38), 24329-24339","doi":"10.1021/acsomega.0c02547","pmid":"33015449","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04804","title":"Five Decades of Research on Opioid Peptides: Current Knowledge and Unanswered Questions.","authors":"Fricker, Lloyd D; Margolis, Elyssa B; Gomes, Ivone; Devi, Lakshmi A","year":2020,"journal":"Molecular pharmacology, 98(2), 96-108","doi":"10.1124/mol.120.119388","pmid":"32487735","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04805","title":"Tirzepatide: a glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) dual agonist in development for the treatment of type 2 diabetes.","authors":"Frías, Juan P","year":2020,"journal":"Expert review of endocrinology & metabolism, 15(6), 379-394","doi":"10.1080/17446651.2020.1830759","pmid":"33030356","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04806","title":"Assessing localized conformational stability of antibody-drug conjugate by protein conformation assay.","authors":"Fu, Cexiong; Zhang, Zhaorui; Zhou, Shiyue; Pritts, Wayne A; Zhang, Qunying","year":2020,"journal":"Journal of pharmaceutical and biomedical analysis, 179, 113020","doi":"10.1016/j.jpba.2019.113020","pmid":"31835127","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04807","title":"CAPS2 deficiency induces proopiomelanocortin accumulation in pituitary and affects food intake behavior in mice.","authors":"Fujima, Shuhei; Amemiya, Natsuki; Arima, Tomoki; Sano, Yoshitake; Furuichi, Teiichi","year":2020,"journal":"Neuroscience letters, 738, 135335","doi":"10.1016/j.neulet.2020.135335","pmid":"32891671","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04808","title":"siRNA delivery using amphipathic cell-penetrating peptides into human hepatoma cells.","authors":"Furukawa, Kaori; Tanaka, Masakazu; Oba, Makoto","year":2020,"journal":"Bioorganic & medicinal chemistry, 28(8), 115402","doi":"10.1016/j.bmc.2020.115402","pmid":"32146061","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The researchers designed 12-mer amphipathic helical peptides incorporating α,α-disubstituted amino acids (dAAs) to stabilize their secondary structure. Peptides with hydrophobic dAAs that adopted a helical conformation showed strong cell-penetrating ability.\n\nOne peptide containing dipropylglycine (a specific dAA) formed stable complexes with siRNA at appropriate size and surface charge for intracellular delivery. This peptide achieved effective RNA interference — meaning it successfully silenced target genes — in human hepatoma (liver cancer) cells at remarkably short peptide length and low concentrations of both the peptide and siRNA.","whyItMatters":"siRNA therapies have enormous potential to treat diseases by silencing harmful genes, but getting siRNA into cells remains the central delivery challenge. Most current solutions use lipid nanoparticles, which have limitations. Cell-penetrating peptides offer an alternative delivery platform that could be more precise and versatile. This study's contribution — achieving effective delivery with a very short, well-defined peptide at low concentrations — brings the field closer to practical, peptide-based gene therapy delivery systems.","specificNumbers":"","methodology":"In vitro laboratory study using human hepatoma (liver cancer) cell lines. Researchers designed a series of 12-amino-acid amphipathic helical peptides with different α,α-disubstituted amino acids and characterized their secondary structures in solution. They measured cell-penetrating ability, then tested the peptides' capacity to form complexes with siRNA and deliver it into cancer cells, measuring RNA interference efficiency as the outcome.","limitations":"This is an in vitro study using cancer cell lines only — no animal or human testing was performed. Cell-penetrating ability in a dish doesn't guarantee effectiveness in a living organism, where the peptide would face enzymatic degradation, immune responses, and biodistribution challenges. Specific quantitative data on silencing efficiency and concentrations were not provided in the abstract. Long-term toxicity was not assessed."},{"rthcId":"RPEP-04809","title":"A cell-penetrant lactam-stapled peptide for targeting eIF4E protein-protein interactions.","authors":"Gallagher, Erin E; Menon, Arya; Chmiel, Alyah F; Deprey, Kirsten; Kritzer, Joshua A; Garner, Amanda L","year":2020,"journal":"European journal of medicinal chemistry, 205, 112655","doi":"10.1016/j.ejmech.2020.112655","pmid":"32739551","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04810","title":"Intracellular Delivery of DNA and Protein by a Novel Cell-Permeable Peptide Derived from DOT1L.","authors":"Geng, Jingping; Guo, Xiangli; Wang, Lidan; Nguyen, Richard Q; Wang, Fengqin; Liu, Changbai; Wang, Hu","year":2020,"journal":"Biomolecules, 10(2)","doi":"10.3390/biom10020217","pmid":"32024261","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04811","title":"Neuroimmune/Hematopoietic Axis with Distinct Regulation by the High-Mobility Group Box 1 in Association with Tachykinin Peptides.","authors":"Gergues, Marina; Nagula, Vipul; Bliss, Sarah A; Eljarrah, Adam; Ayer, Seda; Gnanavel, Nikhil; Sinha, Garima; Wu, Qunfeng; Yehia, Ghassan; Greco, Steven J; Qian, Jing; Rameshwar, Pranela","year":2020,"journal":"Journal of immunology (Baltimore, Md. : 1950), 204(4), 879-891","doi":"10.4049/jimmunol.1900582","pmid":"31924647","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04812","title":"Biomimetic peptide enriched nonwoven scaffolds promote calcium phosphate mineralisation.","authors":"Gharaei, Robabeh; Tronci, Giuseppe; Goswami, Parikshit; Davies, Robert P Wynn; Kirkham, Jennifer; Russell, Stephen J","year":2020,"journal":"RSC advances, 10(47), 28332-28342","doi":"10.1039/d0ra02446e","pmid":"35519117","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04813","title":"Tissue-resident macrophages can be generated de novo in adult human skin from resident progenitor cells during substance P-mediated neurogenic inflammation ex vivo.","authors":"Gherardini, Jennifer; Uchida, Youhei; Hardman, Jonathan A; Chéret, Jérémy; Mace, Kimberly; Bertolini, Marta; Paus, Ralf","year":2020,"journal":"PloS one, 15(1), e0227817","doi":"10.1371/journal.pone.0227817","pmid":"31971954","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04814","title":"Chemotactic activities of vasoactive intestinal peptide, neuropeptide Y and substance P in Leishmania braziliensis.","authors":"Giammarressi, Michelle; Vanegas, Oriana; Febres, Anthony; Silva-López, Adrián; López, Emilia Diaz; Ponte-Sucre, Alicia","year":2020,"journal":"Experimental parasitology, 219, 108009","doi":"10.1016/j.exppara.2020.108009","pmid":"33007296","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04815","title":"Backbone Cyclization Turns a Venom Peptide into a Stable and Equipotent Ligand at Both Muscle and Neuronal Nicotinic Receptors.","authors":"Giribaldi, Julien; Haufe, Yves; Evans, Edward R J; Amar, Muriel; Durner, Anna; Schmidt, Casey; Faucherre, Adèle; Moha Ou Maati, Hamid; Enjalbal, Christine; Molgó, Jordi; Servent, Denis; Wilson, David T; Daly, Norelle L; Nicke, Annette; Dutertre, Sébastien","year":2020,"journal":"Journal of medicinal chemistry, 63(21), 12682-12692","doi":"10.1021/acs.jmedchem.0c00957","pmid":"33063995","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Backbone cyclization of α-conotoxin CIA produced analogues that retained low nanomolar potency at muscle-type nicotinic receptors while gaining up to 52-fold higher potency at the neuronal α3β2 subtype (IC50 1.3 nM). The cyclic analogues also showed greatly improved resistance to degradation in human serum. When tested in zebrafish, the peptides were highly paralytic both by injection (adults) and bath application (larvae), demonstrating barrier-crossing ability and efficient uptake — unusual properties for peptides of this size.","whyItMatters":"Venom peptides are a rich source of potential drugs, but their clinical use is typically limited by rapid breakdown in the body and poor absorption. This study shows that a simple chemical modification — connecting the peptide's backbone into a loop — can simultaneously solve stability problems and unexpectedly enhance potency at a key receptor subtype. This approach could be broadly applied to other venom-derived peptide drug candidates.","specificNumbers":"","methodology":"Researchers designed cyclic analogues of α-conotoxin CIA using backbone cyclization. They tested the analogues' potency against muscle-type and neuronal (α3β2) nicotinic acetylcholine receptors, measured their stability in human serum, determined their 3D structures using NMR spectroscopy, and assessed their biological activity in vivo using zebrafish injection and bath application models.","limitations":"The in vivo testing was limited to zebrafish models, which, while useful for demonstrating bioactivity and barrier crossing, do not directly predict mammalian pharmacokinetics or therapeutic potential. No mammalian in vivo studies were reported. The structural explanations for the gain in α3β2 potency are based on NMR comparison and remain speculative without co-crystal structures with the receptor."},{"rthcId":"RPEP-04816","title":"Cardiac natriuretic peptides.","authors":"Goetze, Jens P; Bruneau, Benoit G; Ramos, Hugo R; Ogawa, Tsuneo; de Bold, Mercedes Kuroski; de Bold, Adolfo J","year":2020,"journal":"Nature reviews. Cardiology, 17(11), 698-717","doi":"10.1038/s41569-020-0381-0","pmid":"32444692","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04817","title":"Cardiovascular safety outcomes of once-weekly GLP-1 receptor agonists in people with type 2 diabetes.","authors":"Goldman, Jennifer D","year":2020,"journal":"Journal of clinical pharmacy and therapeutics, 45 Suppl 1(Suppl 1), 61-72","doi":"10.1111/jcpt.13226","pmid":"32910492","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04818","title":"Advances in the use of cell penetrating peptides for respiratory drug delivery.","authors":"Gomes Dos Reis, Larissa; Traini, Daniela","year":2020,"journal":"Expert opinion on drug delivery, 17(5), 647-664","doi":"10.1080/17425247.2020.1739646","pmid":"32138567","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04819","title":"Delivery of pDNA to lung epithelial cells using PLGA nanoparticles formulated with a cell-penetrating peptide: understanding the intracellular fate.","authors":"Gomes Dos Reis, Larissa; Lee, Wing-Hin; Svolos, Maree; Moir, Lyn M; Jaber, Rima; Engel, Andrea; Windhab, Norbert; Young, Paul M; Traini, Daniela","year":2020,"journal":"Drug development and industrial pharmacy, 46(3), 427-442","doi":"10.1080/03639045.2020.1724134","pmid":"32070151","tags":["cell-penetrating","peptide-delivery"],"studyType":"In vitro (cell culture)","evidenceStrength":"preliminary","keyFinding":"The cell-penetrating peptide (CPP) was the key ingredient. Without CPP, the PLGA nanoparticles carrying plasmid DNA showed minimal cell uptake. With CPP attached, 84% of Beas-2B cells and 97% of A549 lung cancer cells internalized the nanoparticles within just 3 hours.\n\nThe particles entered cells mainly through clathrin-mediated endocytosis, a common cellular intake pathway. Once inside, the particles appeared to escape the endosome compartment, which is critical for the DNA cargo to reach its target. The delivered DNA produced green fluorescent protein (eGFP) in Beas-2B cells after 96 hours, confirming functional gene delivery.\n\nThe nanoparticles released about 50% of their DNA cargo in the first 24 hours, with encapsulation efficiency high enough to be practical.","whyItMatters":"Delivering genes to the lungs is a major goal for treating diseases like cystic fibrosis and lung cancer. The challenge is getting DNA past cell membranes intact. This study shows that adding a cell-penetrating peptide to biodegradable nanoparticles dramatically boosts delivery to lung cells, offering a potential platform for inhaled gene therapies.","specificNumbers":"97% A549 uptake, 84% Beas-2B uptake at 3h; 50% DNA release at 24h; eGFP expression at 96h","methodology":"This was a lab-based (in vitro) study using two lung cell lines: A549 (lung cancer cells) and Beas-2B (normal bronchial cells). Researchers made PLGA nanoparticles using a double-emulsion technique, then characterized their size, surface charge, DNA release profile, and encapsulation efficiency. They tracked cellular uptake using fluorescence, studied which intake pathways the cells used with chemical inhibitors, and confirmed gene expression by detecting eGFP protein.","limitations":"This was tested only in cell cultures, not in living animals or humans. The two cell lines used (A549 and Beas-2B) grow in flat layers and do not replicate the complexity of actual lung tissue with its mucus barriers, immune cells, and airflow. Gene expression was only confirmed in one cell line. No data on how long the gene expression lasts or whether the system would work when inhaled."},{"rthcId":"RPEP-04820","title":"Biased signaling by endogenous opioid peptides.","authors":"Gomes, Ivone; Sierra, Salvador; Lueptow, Lindsay; Gupta, Achla; Gouty, Shawn; Margolis, Elyssa B; Cox, Brian M; Devi, Lakshmi A","year":2020,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 117(21), 11820-11828","doi":"10.1073/pnas.2000712117","pmid":"32393639","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04821","title":"Substance P induces sympathetic immune response in the contralateral eye after the first eye cataract surgery in type 2 diabetic patients.","authors":"Gong, Xianhui; Ren, Yueping; Fang, Xiuxiu; Cai, Junyong; Song, E","year":2020,"journal":"BMC ophthalmology, 20(1), 339","doi":"10.1186/s12886-020-01598-4","pmid":"32811461","tags":["neuropeptides","inflammation"],"studyType":"Prospective randomized clinical study","evidenceStrength":"moderate","keyFinding":"In diabetic patients, Substance P (SP) and MCP-1 levels both rose significantly in the contralateral (opposite) eye after the first cataract surgery, whether the second surgery was 1 day or 1 week later (P ≤ 0.040). The SP increase in diabetic patients was significantly higher than in non-diabetic patients (P ≤ 0.030) at both time intervals.\n\nMCP-1, a protein that attracts immune cells, also increased more in diabetic patients, reaching statistical significance in the 1-week interval group (P = 0.042).\n\nThis suggests that surgery on one eye triggers a sympathetic inflammatory response in the other eye, and diabetes amplifies this response. This may explain why diabetic patients often report more pain during their second eye surgery.","whyItMatters":"Cataract surgery is one of the most common surgeries worldwide. Many patients need both eyes done. This study reveals that diabetic patients mount an inflammatory response in the unoperated eye, driven by Substance P. Understanding this mechanism could lead to better pain management and timing strategies for sequential cataract surgeries in diabetic patients.","specificNumbers":"51 patients; SP increase P≤0.030 diabetic vs non-diabetic; MCP-1 increase P=0.042 at 1-week interval","methodology":"A prospective randomized clinical study with 51 cataract patients: 22 with type 2 diabetes and 29 without. Patients were randomized to have their second eye surgery at either 1-day or 1-week intervals. Aqueous humor (eye fluid) samples of more than 100 microliters were collected before each surgery. Researchers measured 10 inflammatory markers plus Substance P using Luminex assays and ELISA.","limitations":"The sample size of 51 patients is modest, especially when split into four subgroups (diabetic/non-diabetic crossed with 1-day/1-week). The study only measured two time intervals, so the full time course of the inflammatory response is unknown. The mechanism connecting surgery on one eye to SP release in the other was not directly tested."},{"rthcId":"RPEP-04822","title":"The locus of Action of CGRPergic Monoclonal Antibodies Against Migraine: Peripheral Over Central Mechanisms.","authors":"González-Hernández, Abimael; Marichal-Cancino, Bruno A; García-Boll, Enrique; Villalón, Carlos M","year":2020,"journal":"CNS & neurological disorders drug targets, 19(5), 344-359","doi":"10.2174/1871527319666200618144637","pmid":"32552657","tags":["neuropeptides","pain"],"studyType":"Review","evidenceStrength":"strong","keyFinding":"The review analyzes evidence on four FDA-approved anti-CGRP monoclonal antibodies: erenumab, fremanezumab, galcanezumab, and eptinezumab. All target either CGRP itself or its receptor in the trigeminovascular system.\n\nThe central question is whether these antibodies work inside the brain or outside it. At roughly 150 kDa (150,000 daltons), these molecules are far too large to cross an intact blood-brain barrier (BBB). Multiple studies confirm minimal BBB penetration.\n\nThe evidence points to peripheral mechanisms: the antibodies likely block CGRP signaling at sensory nerve endings in the meninges (brain coverings), at the trigeminal ganglion (a nerve cluster outside the BBB), and in peripheral blood vessels. Some researchers have suggested the antibodies might access areas where the BBB is leaky, such as the area postrema, but this remains debated.","whyItMatters":"Understanding where these drugs work matters for developing better versions. If peripheral action is sufficient, future migraine drugs do not need to cross the blood-brain barrier at all. This simplifies drug design and may reduce side effects. It also helps explain why these antibodies have remarkably clean safety profiles compared to older migraine drugs that act centrally.","specificNumbers":"4 FDA-approved mAbs; ~150 kDa molecular weight; gepant development interrupted by pharmacokinetic issues","methodology":"This is a narrative review summarizing published research on the pharmacology, pharmacokinetics, and mechanisms of action of anti-CGRP monoclonal antibodies. It draws from randomized clinical trials, preclinical animal studies, and pharmacokinetic analyses.","limitations":"As a narrative review, this paper selects and interprets existing evidence rather than generating new data. The question of BBB penetration is not fully settled; some evidence suggests partial BBB disruption during migraine attacks could allow limited antibody access. The review also cannot address long-term effects of blocking peripheral CGRP signaling."},{"rthcId":"RPEP-04823","title":"Phage Display-Based Nanotechnology Applications in Cancer Immunotherapy.","authors":"Goracci, Martina; Pignochino, Ymera; Marchiò, Serena","year":2020,"journal":"Molecules (Basel, Switzerland), 25(4)","doi":"10.3390/molecules25040843","pmid":"32075083","tags":["cancer","peptide-design"],"studyType":"Review","evidenceStrength":"preliminary","keyFinding":"The review highlights three main applications of phage display in cancer immunotherapy. First, phage display identifies mimotopes, peptides that mimic the shape of cancer-specific antigens. These mimotopes can be used as vaccines to train the immune system to recognize real tumors.\n\nSecond, whole phage particles carrying cancer antigens on their surface act as natural vaccine platforms. The virus-like structure of phages triggers strong immune responses on its own, boosting the effect of the attached cancer antigens.\n\nThird, phage display finds small peptides that directly activate immune cells, such as those that stimulate T cells or natural killer cells to attack tumors. Several preclinical studies show these approaches can shrink tumors in animal models.","whyItMatters":"Cancer immunotherapy is transforming oncology, but finding the right targets remains a bottleneck. Phage display can screen billions of peptide variants quickly and cheaply, making it a powerful discovery tool. The technique already won the 2018 Nobel Prize in Chemistry, and its application to cancer vaccines could accelerate development of personalized cancer treatments.","specificNumbers":"Nobel Prize 2018; billions of variants per screen; 3 main immunotherapy applications","methodology":"This is a review article surveying published preclinical studies on phage display applications in cancer immunotherapy. It covers peptide library screening methods, mimotope identification, phage-based vaccines, and peptide effectors of immune function. No new experimental data was generated.","limitations":"Nearly all results described are preclinical, tested in lab dishes and animal models. The review does not discuss the significant challenges of translating phage display-derived vaccines to human clinical trials, including manufacturing scale-up, regulatory hurdles, and the gap between mouse and human immune systems."},{"rthcId":"RPEP-04824","title":"Antimicrobial efficacy of Cecropin A (1-7)- Melittin and Lactoferricin (17-30) against multi-drug resistant Salmonella Enteritidis.","authors":"Gourkhede, Diksha P; Bhoomika, Sirsant; Pathak, Richa; Yadav, Jay Prakash; Nishanth, Dani; Vergis, Jess; Malik, S V S; Barbuddhe, S B; Rawool, D B","year":2020,"journal":"Microbial pathogenesis, 147, 104405","doi":"10.1016/j.micpath.2020.104405","pmid":"32707313","tags":["antimicrobial-peptides","infection"],"studyType":"In vitro","evidenceStrength":"preliminary","keyFinding":"Both antimicrobial peptides showed clear antibacterial activity against three field strains of multi-drug resistant S. Enteritidis in standard lab tests. Minimum inhibitory concentrations (MIC) were 64 micromolar, and minimum bactericidal concentrations (MBC) were 128-256 micromolar, meaning the kill dose was 2-4 times the growth-stopping dose.\n\nThe peptides were stable across a range of conditions: high temperatures (70-90 degrees C), protease exposure (trypsin, proteinase K, lysozyme), varying salt concentrations, and pH range of 4.0 to 8.0. They did not damage red blood cells, showed minimal toxicity to RAW 264.7 macrophage and HEp-2 cells, and were safe for beneficial gut bacteria (L. acidophilus and L. rhamnosus).\n\nThe problem: once S. Enteritidis invaded immune cells (RAW 264.7 macrophages), neither peptide could kill it. They showed bacteriostatic (growth-stopping) effects in macrophages but no significant bactericidal (killing) effect in either cell line (P > 0.05).","whyItMatters":"Antibiotic-resistant Salmonella is a growing public health threat. Antimicrobial peptides are a promising alternative because bacteria rarely develop resistance to them. This study shows these two peptides are effective and safe in solution but reveals a critical limitation: they cannot reach bacteria hiding inside cells. This means they would need to be combined with cell-penetrating strategies to be truly useful.","specificNumbers":"MIC 64µM; MBC 128-256µM; non-hemolytic; no significant intracellular killing (P>0.05)","methodology":"Tested in lab dishes (in vitro). MIC and MBC determined against three multi-drug resistant S. Enteritidis field strains. Stability tested under heat, protease, salt, and pH stress. Safety evaluated via hemolysis assay on sheep red blood cells, cytotoxicity in RAW 264.7 and HEp-2 cells, and effects on beneficial Lactobacillus species. Intracellular killing tested by infecting cells with bacteria, then treating with peptides and counting surviving bacteria over time.","limitations":"Tested only in lab dishes, not in animals or humans. The three S. Enteritidis strains may not represent all resistant variants. The failure to kill intracellular bacteria is a major functional limitation. MIC/MBC values of 64-256 micromolar are relatively high compared to some other AMPs, raising questions about practical dosing."},{"rthcId":"RPEP-04825","title":"Molecular Diversity of Mytilin-Like Defense Peptides in Mytilidae (Mollusca, Bivalvia).","authors":"Greco, Samuele; Gerdol, Marco; Edomi, Paolo; Pallavicini, Alberto","year":2020,"journal":"Antibiotics (Basel, Switzerland), 9(1)","doi":"10.3390/antibiotics9010037","pmid":"31963793","tags":["antimicrobial-peptides","peptide-design"],"studyType":"Bioinformatics/Computational","evidenceStrength":"preliminary","keyFinding":"The study performed a comprehensive bioinformatic search across all available mussel genomes and transcriptomes. The key finding is that mytilin-like peptides are more widespread and diverse than previously recognized.\n\nAll mytilins share a CS-alpha-beta structural scaffold, a common architecture found in defense peptides across nearly all branches of life. Despite low sequence similarity (the actual amino acid letters differ a lot), the backbone shape is conserved and stabilized by four disulfide bonds.\n\nVariations in the alpha-helix size, beta-strand regions, and the positioning of one specific disulfide bond (C1-C5) suggest structural flexibility that could relate to different antimicrobial functions. The discovery of mytilins in Trichomya and Perna mussels extends the known range of these peptides beyond the previously studied Mytilus species.","whyItMatters":"Antimicrobial peptides from marine organisms are a potential source of new antibiotics. Understanding the full diversity of mytilins helps researchers identify the most promising candidates for drug development. The conserved structural scaffold across species also provides insight into how nature designs antimicrobial molecules.","specificNumbers":"4 conserved disulfide bonds; new mytilins in Trichomya and Perna spp.; CS-αβ scaffold universal","methodology":"A bioinformatics study. Researchers searched publicly available genomes and transcriptomes of marine mussels (order Mytilida) for sequences matching mytilin-like patterns. They analyzed structural features, disulfide bond patterns, and evolutionary relationships using computational tools. No wet-lab experiments were performed.","limitations":"This is a purely computational study. The newly identified mytilin sequences have not been experimentally tested for antimicrobial activity. Bioinformatic predictions of structure and function need laboratory validation. The available genome data for many mussel species is still incomplete."},{"rthcId":"RPEP-04826","title":"Abaloparatide followed by alendronate in women ≥80 years with osteoporosis: post hoc analysis of ACTIVExtend.","authors":"Greenspan, Susan L; Fitzpatrick, Lorraine A; Mitlak, Bruce; Wang, Yamei; Harvey, Nicholas C; Deal, Chad; Cosman, Felicia; McClung, Michael","year":2020,"journal":"Menopause (New York, N.Y.), 27(10), 1137-1142","doi":"10.1097/GME.0000000000001593","pmid":"32665529","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04827","title":"A Role for GLP-1 in Treating Hyperphagia and Obesity.","authors":"Grill, Harvey J","year":2020,"journal":"Endocrinology, 161(8)","doi":"10.1210/endocr/bqaa093","pmid":"32516384","tags":["glp-1","weight-loss"],"studyType":"Review","evidenceStrength":"strong","keyFinding":"GLP-1 receptor agonist drugs reduce body weight by activating the same brain circuits that are naturally engaged by gut-derived GLP-1 after eating and by bariatric surgery.","whyItMatters":"With obesity prevalence tripling in 40 years and behavioral interventions frequently failing long-term, GLP-1 receptor agonists represent a biologically-based treatment that addresses the underlying neural mechanisms driving overeating.","specificNumbers":"Obesity nearly tripled in 40 years; GLP-1 made in gut and brain; effects on reward, motivation, and hunger","methodology":"Narrative review of published literature on GLP-1 neurobiology, bariatric surgery outcomes, and GLP-1R agonist clinical data.","limitations":"As a narrative review, this does not include new experimental data. The long-term durability and safety of GLP-1R agonist therapy require continued study."},{"rthcId":"RPEP-04828","title":"Design of human lactoferricin derived antitumor peptides-activity and specificity against malignant melanoma in 2D and 3D model studies.","authors":"Grissenberger, Sarah; Riedl, Sabrina; Rinner, Beate; Leber, Regina; Zweytick, Dagmar","year":2020,"journal":"Biochimica et biophysica acta. Biomembranes, 1862(8), 183264","doi":"10.1016/j.bbamem.2020.183264","pmid":"32151609","tags":["antimicrobial-peptides","cancer"],"studyType":"In vitro","evidenceStrength":"preliminary","keyFinding":"The researchers tested a set of modified di-peptides (doubled versions) derived from LF11, an 11-amino-acid fragment of human lactoferricin. They systematically varied length, positive charge, and hydrophobicity to find the optimal cancer-killing design.\n\nThe winners were R-DIM-P-LF11-215 and DIM-LF11-322, both with a net charge of +9 and moderate hydrophobicity. These showed the highest specific antitumor activity in standard 2D cultures and maintained their cancer-killing specificity in 3D multicellular tumor spheroids (MCTS).\n\nOne peptide, DIM-LF11-339, was highly hydrophobic and killed cancer cells in 2D but performed poorly in 3D. It could only kill cells at the outer edge of tumor spheroids, suggesting that too much hydrophobicity prevents peptides from penetrating into the center of solid tumors.\n\nThe peptides kill cancer cells by targeting phosphatidylserine, a lipid that sits on the outside of cancer cell membranes but stays hidden inside normal cell membranes. This is what gives the peptides their cancer specificity.","whyItMatters":"Most cancer drugs also damage healthy cells. These peptides selectively target a physical difference between cancer and normal cell membranes: the location of phosphatidylserine. The 3D spheroid data is especially valuable because flat cell cultures often overpredict drug effectiveness. The finding that moderate hydrophobicity outperforms high hydrophobicity provides a clear design rule for future peptide drugs.","specificNumbers":"+9 net charge optimal; moderate hydrophobicity best; 3D spheroid penetration failed for highly hydrophobic variant","methodology":"Tested in lab dishes using melanoma cells (in vitro). Standard 2D cell cultures were used first, then 3D multicellular tumor spheroids to better mimic real tumor tissue. Cell viability, apoptosis (programmed cell death), and membrane targeting were measured. Non-cancerous cells served as specificity controls.","limitations":"Tested only on melanoma cells in lab dishes, not in animals or humans. The 3D spheroids are more realistic than flat cultures but still lack blood vessels, immune cells, and the full complexity of real tumors. Only one cancer type (melanoma) was tested. No pharmacokinetic data on how these peptides would behave in a living body."},{"rthcId":"RPEP-04829","title":"Identification of ex vivo catabolites of peptides with doping potential in equine plasma by HILIC-HRMS.","authors":"Guan, Fuyu; Fay, Savannah; Li, Xiaoqing; You, Youwen; Robinson, Mary A","year":2020,"journal":"Drug testing and analysis, 12(6), 771-784","doi":"10.1002/dta.2781","pmid":"32100400","tags":["regulatory","bioavailability"],"studyType":"Analytical/Experimental","evidenceStrength":"moderate","keyFinding":"Of 27 bioactive peptides with chemical protection at both ends (to resist degradation), 13 remained stable after 72 hours at body temperature in horse plasma. The other 14 broke down to varying degrees.\n\nThe researchers identified specific breakdown products (catabolites) for all 14 unstable peptides, including novel catabolites never previously reported for chemotactic peptide, DALDA, dmtDALDA, deltorphins I and II, and several dermorphin analogs.\n\nKey stability rules emerged: a D-amino acid (mirror image of normal) at position 2 or position 1 of a peptide, or next to its C-terminus, protected that end from degradation. But a D-amino acid at position 3 did not help. N-terminal modifications like pyroglutamic acid or N-methylation did not protect the N-terminal end. A C-terminal ethylamide group did protect against carboxypeptidase attack. The C-terminal lysine amide in DALDA, dmtDALDA, and Lys7-dermorphin was unexpectedly vulnerable to plasma enzymes.","whyItMatters":"Peptide doping in horse racing is hard to detect because peptides break down quickly in blood. If testing labs only look for the intact peptide, they will miss it. Knowing the specific breakdown products means labs can test for those instead, catching cheaters who use peptides that would otherwise disappear before testing.","specificNumbers":"27 peptides; 13 stable at 72h; 14 degraded; novel catabolites for 8 peptide types; D-amino acid position rules established","methodology":"Researchers incubated 27 peptides in horse plasma under different conditions (temperature, time) and analyzed breakdown products using HILIC (a type of liquid chromatography) coupled with HRMS (high-resolution mass spectrometry). They predicted theoretical breakdown masses computationally, then confirmed them experimentally by their appearance over time and their fragmentation patterns.","limitations":"This tested peptide stability in horse plasma specifically, and degradation patterns may differ in human plasma or in vivo. The ex vivo (in a tube) conditions do not perfectly replicate what happens inside a living horse, where additional enzymes and clearance mechanisms are present. Only peptides with terminal protection were tested."},{"rthcId":"RPEP-04830","title":"Cathelicidin Mediates a Protective Role of Vitamin D in Ulcerative Colitis and Human Colonic Epithelial Cells.","authors":"Gubatan, John; Mehigan, Gillian A; Villegas, Fernando; Mitsuhashi, Shuji; Longhi, Maria Serena; Malvar, Grace; Csizmadia, Eva; Robson, Simon; Moss, Alan C","year":2020,"journal":"Inflammatory bowel diseases, 26(6), 885-897","doi":"10.1093/ibd/izz330","pmid":"31955203","tags":["cathelicidin","vitamin-d","inflammatory-bowel-disease"],"studyType":"human-and-animal","evidenceStrength":"moderate","keyFinding":"Vitamin D's protective effects in ulcerative colitis (UC) appear to work through cathelicidin, an antimicrobial peptide. In UC patients, higher vitamin D levels correlated with higher cathelicidin levels in both blood and colon tissue, and higher serum cathelicidin was associated with decreased risk of histologic inflammation and clinical relapse. In lab experiments, vitamin D treatment of human colon cells induced cathelicidin production and the anti-inflammatory cytokine IL-10, suppressed the pro-inflammatory cytokine TNF-α, and killed E. coli bacteria — an antimicrobial effect that disappeared when cathelicidin was knocked down. In mice, rectal cathelicidin administration reduced the severity of chemically induced colitis.","whyItMatters":"Vitamin D supplementation has long been associated with better outcomes in inflammatory bowel disease, but the mechanism was unclear. This study identifies cathelicidin as a key mediator — vitamin D triggers colon cells to produce this antimicrobial peptide, which then fights harmful bacteria and reduces inflammation. This opens the possibility of directly targeting the vitamin D-cathelicidin pathway as a treatment for UC.","specificNumbers":"","methodology":"A multi-part study: (1) Measured serum and colonic cathelicidin levels in UC patients and correlated them with clinical outcomes. (2) Treated human colon epithelial cells with active vitamin D and measured cathelicidin, cytokines (IL-10, TNF-α), and antimicrobial activity against E. coli, with siRNA knockdown to confirm cathelicidin's role. (3) Administered intrarectal cathelicidin to mice with DSS-induced colitis and assessed disease severity and gut microbiota changes.","limitations":"The correlation between cathelicidin and reduced inflammation in UC patients was not independent of vitamin D levels or baseline inflammation, making it difficult to separate cathelicidin's independent effect. The mouse model used chemically induced colitis, which differs from human UC. Intrarectal cathelicidin reduced colitis severity but did not reverse the changes in gut microbiota composition caused by colitis."},{"rthcId":"RPEP-04831","title":"Vitamin D and Streptococci: The Interface of Nutrition, Host Immune Response, and Antimicrobial Activity in Response to Infection.","authors":"Guevara, Miriam A; Lu, Jacky; Moore, Rebecca E; Chambers, Schuyler A; Eastman, Alison J; Francis, Jamisha D; Noble, Kristen N; Doster, Ryan S; Osteen, Kevin G; Damo, Steven M; Manning, Shannon D; Aronoff, David M; Halasa, Natasha B; Townsend, Steven D; Gaddy, Jennifer A","year":2020,"journal":"ACS infectious diseases, 6(12), 3131-3140","doi":"10.1021/acsinfecdis.0c00666","pmid":"33170652","tags":["antimicrobial-peptides","immune-function","ll-37"],"studyType":"Review","evidenceStrength":"moderate","keyFinding":"The review connects three bodies of evidence. First, epidemiological data shows vitamin D deficiency is associated with higher risk of streptococcal infections, including pneumonia, meningitis, sepsis, and skin infections.\n\nSecond, vitamin D directly stimulates production of antimicrobial peptides, particularly cathelicidin (LL-37) and lactoferrin. These peptides punch holes in bacterial membranes and modulate immune cell behavior.\n\nThird, vitamin D enhances other innate immune functions: phagocytosis (immune cells physically engulfing bacteria) and oxidative burst (production of reactive oxygen species that kill engulfed bacteria). Together, these mechanisms explain why low vitamin D leaves people more vulnerable to streptococcal infections.","whyItMatters":"Streptococcal infections kill hundreds of thousands of people annually, disproportionately in regions where vitamin D deficiency is common. Understanding how vitamin D supports antimicrobial peptide production could lead to simple, cheap interventions. Vitamin D supplementation costs pennies per day and could reduce infection risk in deficient populations.","specificNumbers":"Cathelicidin and lactoferrin upregulated by vitamin D; deficiency common in low/middle-income countries","methodology":"Narrative review of published epidemiological studies, in vitro experiments, animal models, and clinical data on the interaction between vitamin D, the immune system, and Streptococcus pathogens.","limitations":"Most evidence linking vitamin D to streptococcal outcomes is observational. Observational studies cannot prove that vitamin D deficiency causes infections; other factors common in low-income settings (malnutrition, crowding, limited healthcare) also increase infection risk. Randomized supplementation trials specifically for streptococcal prevention are limited."},{"rthcId":"RPEP-04832","title":"Functional characterization of NLRX1 in rabbit during enterohemorrhagic Escherichia coli infection.","authors":"Guo, Mengjiao; Zhang, Congyue; Zhang, Chengcheng; Zhang, Xiaorong; Wu, Yantao","year":2020,"journal":"Developmental and comparative immunology, 106, 103612","doi":"10.1016/j.dci.2020.103612","pmid":"31962226","tags":["antimicrobial-peptides","immune-function","infection"],"studyType":"In vitro","evidenceStrength":"preliminary","keyFinding":"The researchers cloned rabbit NLRX1 (rNLRX1) for the first time and found it contains a NACHT domain and seven leucine-rich repeats. It was expressed widely across rabbit tissues and increased sharply in liver, spleen, kidney, and colon after EHEC infection.\n\nOverexpressing rNLRX1 suppressed NF-kB signaling, the master switch for inflammation. This reduced production of pro-inflammatory cytokines (IL-1beta, TNF-alpha) and beta-defensins (DEFB114, DEFB124, DEFB125). The result: bacteria grew faster.\n\nKnocking down rNLRX1 had the opposite effect. NF-kB activation increased, cytokines and defensins rose, and EHEC growth was inhibited. This identifies NLRX1 as a negative regulator of antimicrobial defense, essentially a brake pedal on the immune response.","whyItMatters":"EHEC causes severe food poisoning and hemolytic uremic syndrome. Understanding how the immune system regulates its response to EHEC is critical. NLRX1 acts as a double-edged sword: it prevents excessive inflammation (which can damage tissues) but also allows bacteria to proliferate. This trade-off is central to immune regulation.","specificNumbers":"NLRX1 increased in 4 tissues post-infection; 3 beta-defensins suppressed; NF-kB signaling inhibited","methodology":"Laboratory study using rabbit RK-13 cells. Researchers cloned rNLRX1, characterized its structure, measured its expression across rabbit tissues, and used overexpression and siRNA knockdown experiments to study its function during EHEC infection. NF-kB activation, cytokine levels, defensin expression, and bacterial growth were measured.","limitations":"Tested only in rabbit cells, not in live animals or humans. The RK-13 cell line may not fully represent intestinal immune responses where EHEC causes disease. The study does not address whether modulating NLRX1 could be therapeutically useful or what side effects might occur from blocking this immune brake."},{"rthcId":"RPEP-04833","title":"Adiponectin treatment improves insulin resistance in mice by regulating the expression of the mitochondrial-derived peptide MOTS-c and its response to exercise via APPL1-SIRT1-PGC-1α.","authors":"Guo, Qi; Chang, Bo; Yu, Qiong-Li; Xu, Si-Tong; Yi, Xue-Jie; Cao, Shi-Cheng","year":2020,"journal":"Diabetologia, 63(12), 2675-2688","doi":"10.1007/s00125-020-05269-3","pmid":"32880686","tags":["diabetes","hormone-optimization"],"studyType":"Animal study (mice) + in vitro","evidenceStrength":"moderate","keyFinding":"In mice lacking the adiponectin gene (Adipoq-/- knockouts), MOTS-c levels in blood and muscle were significantly lower than normal. This directly links adiponectin to MOTS-c production.\n\nIn muscle cells (C2C12 myotubes), adiponectin treatment increased MOTS-c gene expression. The researchers traced the signaling chain: adiponectin activates APPL1, which activates SIRT1, which activates PGC-1alpha, which drives MOTS-c production. Blocking any step in this chain (with inhibitors or siRNA) stopped the MOTS-c increase.\n\nIn mice on a high-fat diet, both exercise and injected adiponectin or MOTS-c raised MOTS-c levels in blood and muscle. This was accompanied by improved insulin sensitivity, suggesting MOTS-c is a key mediator of adiponectin's metabolic benefits.\n\nOverexpressing SIRT1 amplified the adiponectin effect on MOTS-c, while blocking PGC-1alpha eliminated it. This establishes the APPL1-SIRT1-PGC-1alpha pathway as the mechanism.","whyItMatters":"MOTS-c is a relatively new discovery: a peptide encoded by mitochondrial DNA that influences metabolism. This study reveals how the body naturally regulates MOTS-c production through adiponectin signaling. It positions MOTS-c as a potential drug target for type 2 diabetes and explains part of why exercise improves insulin sensitivity.","specificNumbers":"Adipoq-/- mice: lower MOTS-c; HFD: reduced MOTS-c; exercise and Acrp30 injection: restored MOTS-c; APPL1-SIRT1-PGC-1α pathway confirmed","methodology":"Tested in mice and cell cultures. Used wild-type C57BL/6 mice on high-fat diet, adiponectin knockout mice, and C2C12 muscle cell cultures. Interventions included exercise, injected adiponectin (Acrp30), injected MOTS-c, gene overexpression, siRNA knockdown, and pharmacological inhibitors. Measured MOTS-c mRNA and protein levels, insulin sensitivity markers, and pathway components.","limitations":"Tested in mice, not people. Mouse metabolism differs from human metabolism, and the APPL1-SIRT1-PGC-1alpha pathway may not work identically in humans. The adiponectin knockout model eliminates all adiponectin, which is more extreme than the reduced levels seen in human obesity. Cell culture experiments used C2C12 mouse myotubes, which may not perfectly replicate human muscle biology."},{"rthcId":"RPEP-04834","title":"Hierarchically Imprinted Polymer for Peptide Tag Recognition Based on an Oriented Surface Epitope Approach.","authors":"Gómez-Arribas, Lidia N; Darder, María Del Mar; García, Nuria; Rodriguez, Yoel; Urraca, Javier L; Moreno-Bondi, María C","year":2020,"journal":"ACS applied materials & interfaces, 12(43), 49111-49121","doi":"10.1021/acsami.0c14846","pmid":"32990425","tags":["peptide-design","bioavailability"],"studyType":"In vitro (materials science)","evidenceStrength":"preliminary","keyFinding":"The researchers used a technique called hierarchical imprinting to create synthetic polymers with binding pockets shaped to grab the FLAG peptide tag (DYKDDDDK). They tested two different silane coatings to orient the template peptide correctly during manufacturing.\n\nThe version made with AETAZS silane performed significantly better: 87.4% recovery of the FLAG tag versus only 4.1% non-specific binding. The AEAPMS version recovered 73.4% but had much higher non-specific binding at 23.2%.\n\nComputational modeling revealed why orientation matters. When the template peptide is properly anchored, the imprinted cavities form more precise shapes that better match the target.","whyItMatters":"Purifying proteins tagged with FLAG peptide currently requires expensive antibody-based columns that degrade over time. Molecularly imprinted polymers are cheap, stable, and reusable. A highly selective MIP for FLAG tags could make protein purification more affordable and practical for biotechnology labs.","specificNumbers":"87.4% FLAG tag recovery (AETAZS MIP); 4.1% non-specific binding; 73.4% recovery (AEAPMS MIP)","methodology":"Researchers synthesized molecularly imprinted polymers using a 5-amino acid epitope (DYKDC) from the FLAG tag, immobilized on microporous silica beads coated with two different silanes. They characterized the silane layers using 29Si CP/MAS NMR. The polymers were tested as solid-phase extraction sorbents for FLAG tag recovery, with non-imprinted polymers as controls. Computational molecular modeling explored binding interactions.","limitations":"This was tested with pure peptide solutions, not complex biological mixtures like cell lysates where many competing molecules would be present. Real-world protein purification involves far more challenging conditions. The study did not test how well the MIP performs over repeated uses or how it handles full-length FLAG-tagged proteins versus the short peptide alone."},{"rthcId":"RPEP-04835","title":"Development of Nonpeptidic Inverse Agonists of the Ghrelin Receptor (GHSR) Based on the 1,2,4-Triazole Scaffold.","authors":"Haj Salah, Khoubaib Ben; Maingot, Mathieu; Blayo, Anne-Laure; M'Kadmi, Céline; Damian, Marjorie; Mary, Sophie; Cantel, Sonia; Neasta, Jérémie; Oiry, Catherine; Péraldi-Roux, Sylvie; Fernandez, Gimena; Romero, Guadalupe García; Perello, Mario; Marie, Jacky; Banères, Jean-Louis; Fehrentz, Jean-Alain; Denoyelle, Séverine","year":2020,"journal":"Journal of medicinal chemistry, 63(19), 10796-10815","doi":"10.1021/acs.jmedchem.9b02122","pmid":"32882134","tags":["ghrp","weight-loss","peptide-design"],"studyType":"Medicinal chemistry + animal study","evidenceStrength":"preliminary","keyFinding":"The ghrelin receptor (GHSR) has unusually high constitutive activity, meaning it sends hunger and metabolic signals even when ghrelin is not present. An inverse agonist does not just block the receptor; it actively reduces this baseline signaling.\n\nThe researchers developed a series of compounds based on the 1,2,4-triazole chemical scaffold. By varying substituents at positions 3, 4, and 5, they created highly potent and selective GHSR inverse agonists. These compounds stabilize a specific inactive conformation of the receptor, effectively silencing its constant output.\n\nIn living systems, one of the most promising compounds affected insulin secretion in isolated rat pancreatic islets and counteracted ghrelin's appetite-stimulating effects in mice. This demonstrates both metabolic and appetite-related activity in vivo.","whyItMatters":"Ghrelin is called the hunger hormone. Its receptor (GHSR) is a compelling target for obesity and diabetes, but previous attempts to block it have struggled. Inverse agonists are more powerful than simple blockers because they silence the receptor's constant baseline activity. Small molecules (non-peptides) are easier to develop into pills than peptide-based drugs.","specificNumbers":"Triazole scaffold; positions 3,4,5 varied; lead compound active on insulin and appetite in animals","methodology":"Medicinal chemistry study with in vitro and in vivo testing. Researchers synthesized a library of triazole-based compounds, tested them for GHSR binding affinity and inverse agonist activity using cell-based assays measuring G protein activation. The most promising compounds were tested for effects on insulin secretion in rat pancreatic islets (ex vivo) and on feeding behavior in mice (in vivo).","limitations":"Animal testing was limited (rat islets and mouse feeding). No human safety or efficacy data. The triazole compounds' pharmacokinetics (absorption, distribution, metabolism) were not fully characterized. Long-term effects of suppressing GHSR constitutive activity are unknown and could have unintended consequences on growth hormone and glucose regulation."},{"rthcId":"RPEP-04836","title":"Intracellular delivery of a peptide nucleic acid-based hybrid of an autophagy inducing peptide with a cell-penetrating peptide.","authors":"Hakata, Yoshiyuki; Ishikawa, Suzuka; Ohtsuki, Takashi; Miyazawa, Masaaki; Kitamatsu, Mizuki","year":2020,"journal":"Organic & biomolecular chemistry, 18(10), 1978-1986","doi":"10.1039/c9ob02559f","pmid":"32104826","tags":["cell-penetrating","peptide-delivery"],"studyType":"In vitro (proof-of-concept)","evidenceStrength":"preliminary","keyFinding":"The core problem: cell-penetrating peptides (CPPs) have positive charges that can interfere with the function of attached cargo peptides inside cells. Direct conjugation often does not work reliably.\n\nThe solution: an 8-unit PNA sequence conjugated to octa-arginine CPP (PNA1-CPP) paired with a complementary PNA attached to an autophagy-inducing peptide (PNA2-AIP). The two PNA strands hybridized, forming a stable 1:1 complex that kept the functional peptide connected to the CPP during delivery.\n\nOnce inside cells, at least some of the PNA1-CPP/PNA2-AIP complexes dissociated, releasing the functional AIP from the positively charged CPP. The released PNA2-AIP induced significantly more autophagy than AIP directly conjugated to CPP (CPP-AIP). The PNA hybrid system also caused minimal cell death.","whyItMatters":"Getting therapeutic peptides inside cells is one of the biggest challenges in peptide drug development. This PNA-based system solves a specific problem: CPP charges interfering with cargo function. By acting as releasable molecular glue, PNAs could become a general platform for intracellular peptide delivery.","specificNumbers":"8-mer PNA bridge; 1:1 hybrid; improved autophagy vs direct conjugation; minimal cytotoxicity","methodology":"In vitro cell culture study. Researchers synthesized PNA-peptide conjugates using solid-phase peptide synthesis, confirmed 1:1 hybrid formation, measured cellular uptake, tracked intracellular dissociation, quantified autophagy induction (compared to direct CPP-AIP conjugate), and assessed cell viability.","limitations":"Tested in one cell type with one cargo peptide (autophagy inducer). The generalizability to other functional peptides and cell types is unknown. The extent of intracellular PNA dissociation (\"at least some portion\") was not fully quantified. No in vivo testing. PNA synthesis adds cost and complexity to the system."},{"rthcId":"RPEP-04837","title":"Immunostimulatory effects on THP-1 cells by peptide or protein pharmaceuticals associated with injection site reactions.","authors":"Hamamura-Yasuno, Eri; Aida, Tetsuo; Tsuchiya, Yoshimi; Mori, Kazuhiko","year":2020,"journal":"Journal of immunotoxicology, 17(1), 59-66","doi":"10.1080/1547691X.2020.1727071","pmid":"32091282","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04838","title":"Acute Exenatide Therapy Attenuates Postprandial Vasodilation in Humans with Prediabetes: A Randomized Controlled Trial.","authors":"Hamidi, Vala; Riggs, Kayla; Zhu, Liang; Bermudez Saint Andre, Karla; Westby, Christian; Coverdale, Sara; Dursteler, Amy; Wang, Hongyu; Miller Iii, Charles; Taegtmeyer, Heinrich; Gutierrez, Absalon D","year":2020,"journal":"Metabolic syndrome and related disorders, 18(5), 225-233","doi":"10.1089/met.2019.0102","pmid":"32228379","tags":["exenatide","glp-1","cardiovascular"],"studyType":"Randomized controlled crossover trial","evidenceStrength":"preliminary","keyFinding":"Exenatide significantly attenuated resting forearm blood flow (FBF) at 3 hours after the meal (P = 0.003) and showed a trend at 6 hours (P = 0.056) compared to placebo. This means exenatide blunted the vasodilation (blood vessel widening) that normally happens after eating.\n\nExenatide also had beneficial metabolic effects: it prevented the post-meal glucose spike (glucose actually decreased at 2 hours while it rose with placebo and saxagliptin) and abated the transient triglyceride increase. Only the exenatide group did not show a significant insulin surge.\n\nNo differences were found in peak forearm blood flow, plasma nitrotyrosine (an oxidative stress marker), or plasma 8-iso-prostaglandin F2alpha between groups. Free fatty acids declined in all groups but less markedly with exenatide.\n\nThe researchers concluded the vascular effects were primarily endothelium-independent, meaning exenatide altered blood flow through mechanisms other than the vessel lining's nitric oxide system.","whyItMatters":"Prediabetes already involves blood vessel damage. Understanding how GLP-1 drugs affect blood vessels in this population matters for cardiovascular safety and benefit. The finding that exenatide reduces post-meal vasodilation is complex: it could reflect reduced metabolic demand (less glucose and triglyceride to process) rather than vascular harm.","specificNumbers":"n=15; resting FBF reduced P=0.003 at 3h; glucose decreased with exenatide; triglyceride spike abated","methodology":"Randomized, crossover, double-blinded trial with 15 obese adults with prediabetes. Each participant received all three treatments (exenatide, saxagliptin, placebo) on separate occasions with a standardized high-fat meal. Forearm blood flow measured by strain gauge venous occlusion plethysmography. Blood samples taken for metabolic and vascular markers.","limitations":"Very small sample (15 people). Single acute dose, not chronic treatment. Forearm blood flow is a surrogate marker that may not reflect coronary or cerebral vascular effects. The crossover design is a strength but cannot account for all carryover effects. No long-term outcomes measured."},{"rthcId":"RPEP-04839","title":"Conjugation Site Analysis by MS/MS Protein Sequencing.","authors":"Han, Linjie; Zhao, Yanqun; Zhang, Qunying","year":2020,"journal":"Methods in molecular biology (Clifton, N.J.), 2078, 221-233","doi":"10.1007/978-1-4939-9929-3_15","pmid":"31643060","tags":["peptide-design","bioavailability"],"studyType":"Methods paper","evidenceStrength":"moderate","keyFinding":"The protocol addresses a technical challenge in ADC development: hydrophobic drug-loaded peptides tend to precipitate out of solution during standard peptide mapping, making them invisible to mass spectrometry.\n\nThe improved method includes modifications to sample preparation that keep hydrophobic drug-loaded peptides dissolved, enables better chromatographic separation so these peptides are not lost, and uses diagnostic fragmentation ions from the drug payload to unambiguously identify conjugation sites in the LC-MS/MS data.\n\nThis allows researchers to map exactly which amino acids on the antibody have drugs attached, which is critical for understanding ADC potency and safety.","whyItMatters":"Antibody-drug conjugates are a growing class of cancer drugs (14+ FDA-approved as of 2024). Where the drug attaches to the antibody affects how well the ADC works and how toxic it is. Accurate conjugation site mapping is essential for ADC quality control and development. This improved protocol solves a real analytical problem.","specificNumbers":"LC-MS/MS-based; improved hydrophobic peptide handling; diagnostic fragmentation ion identification","methodology":"Methods paper describing a peptide mapping protocol. Monoclonal antibodies with drug-linker conjugates are enzymatically digested into peptide fragments, separated by liquid chromatography, and analyzed by tandem mass spectrometry (LC-MS/MS). The paper covers sample preparation, LC-MS/MS setup, and both automated and manual data processing.","limitations":"This is a methods paper, not a discovery study. It describes a protocol but does not compare its performance quantitatively to other methods. The applicability to different ADC types with different linker chemistries would need to be validated case by case."},{"rthcId":"RPEP-04840","title":"Oral semaglutide versus injectable glucagon-like peptide-1 receptor agonists: a cost of control analysis.","authors":"Hansen, B B; Nuhoho, S; Ali, S N; Dang-Tan, T; Valentine, W J; Malkin, S J P; Hunt, B","year":2020,"journal":"Journal of medical economics, 23(6), 650-658","doi":"10.1080/13696998.2020.1722678","pmid":"31990244","tags":["semaglutide","glp-1","diabetes"],"studyType":"Cost-effectiveness analysis","evidenceStrength":"moderate","keyFinding":"The cost-of-control analysis compared oral semaglutide 14 mg against six injectable GLP-1 receptor agonists for type 2 diabetes. The calculation divides annual drug cost by the proportion of patients reaching HbA1c targets.\n\nFor the HbA1c ≤6.5% target, costs per patient achieving control: injectable semaglutide 1 mg was cheapest at $15,430, followed by oral semaglutide 14 mg at $17,383. All others (dulaglutide, exenatide once-weekly and twice-daily, liraglutide, lixisenatide) cost more per controlled patient.\n\nFor HbA1c <7.0%: injectable semaglutide 1 mg led at $12,627, followed by oral semaglutide at $13,493. The pattern was consistent.\n\nOral semaglutide was likely cost-effective versus all comparators except injectable semaglutide. This matters because some patients strongly prefer pills over injections.","whyItMatters":"Many patients with type 2 diabetes avoid injectable GLP-1 drugs despite their effectiveness. Oral semaglutide (Rybelsus) removes the injection barrier. This analysis shows the pill form is cost-effective compared to most injectables, supporting its use in patients who prefer oral medication.","specificNumbers":"$15,430 injectable sema; $17,383 oral sema per patient at HbA1c≤6.5%; oral sema cost-effective vs 5/6 injectables","methodology":"Cost-of-control analysis using efficacy data from the PIONEER clinical trial program and a published network meta-analysis. Annual US treatment costs were divided by the proportion of patients achieving HbA1c targets (≤6.5% and <7.0%). This is a short-term cost-effectiveness model, not a full health economic evaluation with quality-of-life or long-term outcomes.","limitations":"This is a short-term model based on blood sugar targets only. It does not account for weight loss, cardiovascular benefits, or quality of life, all of which differ among GLP-1 drugs. Drug pricing varies by country and payer. The analysis uses US list prices, which may not reflect negotiated prices. No sensitivity analysis for price changes was described in the abstract."},{"rthcId":"RPEP-04841","title":"Dairy products influence gut hormone secretion and appetite differently: A randomized controlled crossover trial.","authors":"Hansson, Patrik; Holven, Kirsten B; Øyri, Linn K L; Brekke, Hilde K; Gjevestad, Gyrd O; Rehfeld, Jens F; Raza, Ghulam S; Herzig, Karl-Heinz; Ulven, Stine M","year":2020,"journal":"Journal of dairy science, 103(2), 1100-1109","doi":"10.3168/jds.2019-16863","pmid":"31759587","tags":["bioactive-food-peptides","glp-1"],"studyType":"Randomized controlled crossover trial","evidenceStrength":"moderate","keyFinding":"Despite identical fat content (45 grams, about 60% of meal calories), the four dairy products produced different hormonal and appetite responses.\n\nCheese stood out: it triggered higher plasma pancreatic polypeptide (PP) than butter or whipped cream (measured as incremental area under the curve over 6 hours). Cheese also produced higher cholecystokinin (CCK) than whipped cream.\n\nWhipped cream produced the most appetite at 4 hours (compared to cheese and sour cream) and at 6 hours (compared to cheese and butter). This means cheese was the most satiating dairy product, and whipped cream was the least.\n\nNo significant meal effects were found for hunger ratings, satiety ratings, plasma PYY (peptide YY), or plasma ghrelin. The differences were specific to PP, CCK, and appetite VAS scores.","whyItMatters":"All fats are not equal for appetite control. The food matrix matters. Cheese and whipped cream have the same fat but different protein content, texture, and structure. These physical differences change how the gut processes fat and sends satiety signals to the brain. This has practical implications for dietary advice about dairy and weight management.","specificNumbers":"47 adults; 45g fat/meal; cheese: higher PP vs butter/whipped cream, higher CCK vs whipped cream; whipped cream: highest appetite at 4h/6h","methodology":"Randomized controlled crossover study with 47 healthy adults (70% women). Each participant ate all four dairy meals on separate occasions. Blood samples for gut hormones (CCK, PP, PYY, ghrelin) collected at 0, 2, 4, and 6 hours. Appetite measured by visual analog scale (VAS) after meals and at 4 and 6 hours. Hormone data analyzed as incremental area under the curve in a mixed model.","limitations":"The study measured appetite and hormones but did not track actual food intake afterward, which is the real-world outcome that matters. Only four dairy products were tested, and they differ in more than just matrix (protein, calcium, and fermentation status also vary). The 6-hour window may miss longer-term effects. The sample was 70% women, which may limit generalizability."},{"rthcId":"RPEP-04842","title":"Five subfamilies of β-defensin genes are present in salmonids: Evolutionary insights and expression analysis in Atlantic salmon Salmo salar.","authors":"Harte, Anna; Tian, Guangming; Xu, Qiaoqing; Secombes, Christopher John; Wang, Tiehui","year":2020,"journal":"Developmental and comparative immunology, 104, 103560","doi":"10.1016/j.dci.2019.103560","pmid":"31758960","tags":["antimicrobial-peptides","immune-function"],"studyType":"Genomics/Expression analysis","evidenceStrength":"moderate","keyFinding":"Seven beta-defensin genes (BD1a-b, BD2-4, BD5a-b) were characterized in Atlantic salmon, with BD1b and BD5 also newly identified in rainbow trout. Genomic analysis across salmonids revealed up to seven BD genes per species, organized into five subfamilies.\n\nThe evolutionary picture was clear: BD1-2 and BD4-5 exist in primitive bony fish, but advanced bony fish lost one chromosomal region and retained only BD1 and/or BD5. BD3 is found only in salmonids, making it a lineage-specific innovation. Fish beta-defensins have a unique three-exon gene structure different from mammalian defensins.\n\nExpression patterns were unexpected. Traditional immune organs (head kidney, spleen) showed low-level expression. Instead, at least one BD gene was highly expressed in mucosal tissues, heart, blood, and liver. This suggests these peptides serve as frontline defenders at body surfaces and in circulation.","whyItMatters":"Atlantic salmon is one of the most farmed fish globally, and disease is a major cost. Understanding the defensin arsenal helps develop disease-resistant breeding lines and informs vaccine design. The finding that defensins are most active at mucosal surfaces matches where pathogens first contact the fish.","specificNumbers":"7 BD genes; 5 subfamilies; BD3 salmonid-specific; highest expression in mucosal tissues, heart, blood, liver","methodology":"Bioinformatics and molecular biology study. Researchers used genome and transcriptome databases to identify BD genes across salmonid species, performed phylogenetic analysis, and measured gene expression across Atlantic salmon tissues using quantitative methods.","limitations":"Expression was measured in healthy fish. How these genes respond during actual infection was not tested. The bioinformatic identification of BDs in other salmonid species relies on genome assemblies that may be incomplete. Functional antimicrobial testing of the individual peptides was not performed."},{"rthcId":"RPEP-04843","title":"Effects of Novel Dual GIP and GLP-1 Receptor Agonist Tirzepatide on Biomarkers of Nonalcoholic Steatohepatitis in Patients With Type 2 Diabetes.","authors":"Hartman, Mark L; Sanyal, Arun J; Loomba, Rohit; Wilson, Jonathan M; Nikooienejad, Amir; Bray, Ross; Karanikas, Chrisanthi A; Duffin, Kevin L; Robins, Deborah A; Haupt, Axel","year":2020,"journal":"Diabetes care, 43(6), 1352-1355","doi":"10.2337/dc19-1892","pmid":"32291277","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04844","title":"Pathophysiologic mechanisms of itch in bullous pemphigoid.","authors":"Hashimoto, Takashi; Kursewicz, Christina Dorothy; Fayne, Rachel Alison; Nanda, Sonali; Shah, Serena Maya; Nattkemper, Leigh; Yokozeki, Hiroo; Yosipovitch, Gil","year":2020,"journal":"Journal of the American Academy of Dermatology, 83(1), 53-62","doi":"10.1016/j.jaad.2019.07.060","pmid":"31351883","tags":["neuropeptides","inflammation","skin-repair"],"studyType":"Observational (cross-sectional)","evidenceStrength":"preliminary","keyFinding":"Itch severity in bullous pemphigoid correlates with eosinophils, substance P, neurokinin 1 receptor, IL-31 signaling, IL-13, periostin, and basophils, while mast cells and TRPV1 were not significantly correlated.","whyItMatters":"Identifying specific neuropeptide and immune pathways driving itch in BP could lead to targeted therapies like NK1R antagonists or anti-IL-31 drugs, replacing broad immunosuppression.","specificNumbers":"24 BP patients; 6 controls; itch correlated with SP, NK1R, IL-31RA, eosinophils, IL-13, periostin, basophils","methodology":"Immunofluorescence staining of skin lesions from 24 BP patients and 6 healthy controls, with correlation analysis between mediator expression and itch severity.","limitations":"Small sample size (30 total). Cross-sectional design cannot establish causation. Limited to immunofluorescence analysis without functional assays."},{"rthcId":"RPEP-04845","title":"Expression of placenta-specific 1 and its potential for eliciting anti-tumor helper T-cell responses in head and neck squamous cell carcinoma.","authors":"Hayashi, Ryusuke; Nagato, Toshihiro; Kumai, Takumi; Ohara, Kenzo; Ohara, Mizuho; Ohkuri, Takayuki; Hirata-Nozaki, Yui; Harabuchi, Shohei; Kosaka, Akemi; Nagata, Marino; Yajima, Yuki; Yasuda, Syunsuke; Oikawa, Kensuke; Kono, Michihisa; Kishibe, Kan; Takahara, Miki; Katada, Akihiro; Hayashi, Tatsuya; Celis, Esteban; Harabuchi, Yasuaki; Kobayashi, Hiroya","year":2020,"journal":"Oncoimmunology, 10(1), 1856545","doi":"10.1080/2162402X.2020.1856545","pmid":"33457076","tags":["cancer","peptide-design"],"studyType":"Preclinical immunology","evidenceStrength":"preliminary","keyFinding":"A PLAC1-derived peptide epitope (PLAC131-50) stimulates promiscuous helper T cell responses that kill PLAC1-positive HNSCC cells in an HLA-DR-restricted manner, with reactive T cells detected in patient blood.","whyItMatters":"Identifying a promiscuous peptide epitope that works across multiple HLA types means PLAC1-based immunotherapy could benefit a broader patient population.","specificNumbers":"74.5% oropharyngeal, 51.9% oral tumors express PLAC1; PLAC131-50 promiscuous across HLA-DR; patient blood T cells reactive","methodology":"Tumor tissue immunohistochemistry for PLAC1 expression, peptide binding assays, T cell stimulation assays, and cytotoxicity assays against HNSCC cell lines.","limitations":"Preclinical study without in vivo validation. T cell responses were measured in vitro and may not reflect therapeutic efficacy in patients."},{"rthcId":"RPEP-04846","title":"Overexpression of TIMP3 inhibits discogenic pain by suppressing angiogenesis and the expression of substance P in nucleus pulposus.","authors":"He, Mingwei; Pang, Jinlei; Sun, Haiyan; Zheng, Guanrong; Lin, Yan; Ge, Weipeng","year":2020,"journal":"Molecular medicine reports, 21(3), 1163-1171","doi":"10.3892/mmr.2020.10922","pmid":"31922222","tags":["neuropeptides","pain","inflammation"],"studyType":"In vitro + animal model","evidenceStrength":"preliminary","keyFinding":"Inflammation reduced TIMP3 expression in nucleus pulposus (NP) cells, the cells at the center of spinal discs. When TIMP3 was boosted using an adenovirus delivery system, several things happened:\n\nAngiogenesis was suppressed: endothelial cell migration and tube formation (both measures of blood vessel growth) were inhibited. This happened without changing VEGF levels, a common angiogenesis driver.\n\nThe mechanism involved TACE (TNF-alpha converting enzyme). TIMP3 reduced TACE expression, which blocked TACE-mediated activation of TNF-alpha, a key inflammatory molecule.\n\nSubstance P expression was reduced in the NP tissue, as confirmed by immunohistochemical staining of intervertebral discs. Since Substance P transmits pain signals from nerve endings growing into damaged discs, reducing it could directly decrease pain perception.\n\nThe blood vessel and nerve ingrowth into damaged discs is believed to be a major cause of discogenic pain. TIMP3 appears to block both.","whyItMatters":"Low back pain affects hundreds of millions of people. Discogenic pain, where damaged discs grow new blood vessels and nerve endings that transmit pain, accounts for about half of cases. TIMP3 addresses both problems simultaneously: it blocks blood vessel growth and reduces the pain peptide Substance P. This dual action makes it a promising therapeutic target.","specificNumbers":"50% of LBP is discogenic; TIMP3 suppressed angiogenesis and Substance P; TACE/TNF-α pathway confirmed; VEGF unaffected","methodology":"Combined in vitro and in vivo study. Cell experiments used nucleus pulposus cells with adenovirus-mediated TIMP3 overexpression. Angiogenesis measured by endothelial cell migration and tube formation assays. Protein expression analyzed by PCR, immunohistochemistry, and Western blot. Animal model used for in vivo confirmation of Substance P reduction.","limitations":"The in vivo component used an animal model that may not fully replicate human disc degeneration. Adenovirus-mediated gene delivery is a proof of concept, not a practical clinical approach. Long-term effects of TIMP3 overexpression in discs are unknown. The study does not measure actual pain behavior, only molecular markers of pain signaling."},{"rthcId":"RPEP-04847","title":"Dietary biotin deficiency decreased growth performance and impaired the immune function of the head kidney, spleen and skin in on-growing grass carp (Ctenopharyngodon idella).","authors":"He, Peng; Jiang, Wei-Dan; Liu, Xiang-An; Feng, Lin; Wu, Pei; Liu, Yang; Jiang, Jun; Tan, Bei-Ping; Yang, Qi-Hui; Kuang, Sheng-Yao; Tang, Ling; Zhou, Xiao-Qiu","year":2020,"journal":"Fish & shellfish immunology, 97, 216-234","doi":"10.1016/j.fsi.2019.12.033","pmid":"31857225","tags":["antimicrobial-peptides","immune-function"],"studyType":"Controlled feeding trial + bacterial challenge","evidenceStrength":"moderate","keyFinding":"Biotin deficiency at 0.012 mg/kg diet caused a cascade of immune impairments across the head kidney, spleen, and skin of grass carp:\n\nAntimicrobial peptides were reduced: LEAP-2A, LEAP-2B, hepcidin, beta-defensin-1, and mucin 2 all had lower mRNA levels. These peptides form the first line of defense against bacterial invasion.\n\nInnate immune function declined: lysozyme activity, acid phosphatase activity, complement C3 and C4, and immunoglobulin M all decreased.\n\nInflammation went up: pro-inflammatory cytokines (IL-1beta, IL-6, IL-8, IL-12p40, IL-15, IL-17D, TNF-alpha, IFN-gamma2) increased through NF-kB signaling. Anti-inflammatory cytokines (IL-4/13A, IL-10, IL-11, TGF-beta1) decreased through impaired TOR signaling.\n\nOptimal biotin levels for growth, lesion prevention, and immune function ranged from 0.210 to 0.245 mg/kg diet.","whyItMatters":"Grass carp is the most farmed freshwater fish in the world. Biotin is a common feed additive but optimal levels for immune function were unknown. This study shows biotin is not just a growth vitamin; it directly supports antimicrobial peptide production and balanced immune responses. Biotin deficiency creates a double problem: weaker antimicrobial defense and more damaging inflammation.","specificNumbers":"540 fish; 6 biotin levels; 70 days + 6-day challenge; 5 AMPs reduced; optimal 0.21-0.25 mg/kg","methodology":"Controlled feeding trial with 540 grass carp (starting weight ~117g) fed six biotin levels (0.012 to 0.518 mg/kg) for 70 days. After the feeding period, fish were challenged with Aeromonas hydrophila for 6 days. Gene expression, enzyme activities, and immune markers measured in head kidney, spleen, and skin.","limitations":"Only grass carp were tested; results may not apply to other fish species. The extreme biotin deficiency level (0.012 mg/kg) is unlikely in commercial feeds, though suboptimal levels are possible. Gene expression changes do not always translate to proportional protein level changes. The bacterial challenge used a single pathogen."},{"rthcId":"RPEP-04848","title":"Fluorescent Peptide Dendrimers for siRNA Transfection: Tracking pH Responsive Aggregation, siRNA Binding, and Cell Penetration.","authors":"Heitz, Marc; Zamolo, Susanna; Javor, Sacha; Reymond, Jean-Louis","year":2020,"journal":"Bioconjugate chemistry, 31(6), 1671-1684","doi":"10.1021/acs.bioconjchem.0c00231","pmid":"32421327","tags":["cell-penetrating","peptide-delivery"],"studyType":"In vitro (mechanistic)","evidenceStrength":"preliminary","keyFinding":"The researchers created peptide dendrimer variants carrying fluorescent labels in their core. These labeled versions maintained the same siRNA transfection efficiency, pH-dependent aggregation, siRNA binding, and secondary structures as unlabeled dendrimers.\n\nFRET (fluorescence resonance energy transfer) experiments revealed the delivery mechanism in detail: at pH 7.4 (normal cellular pH), dendrimers and siRNA are tightly packed together in nanoparticles. At pH 5.0 (endosomal pH), the complex loosens and dendrimers are released into solution.\n\nAt this acidic pH, the dendrimers destabilize endosomal membranes, enabling escape into the cytoplasm where siRNA can silence target genes.\n\nColocalization studies showed dendrimers and siRNA stay together throughout the uptake process, separating only after reaching acidic endosomes. This pH-triggered release mechanism is what makes the system effective.","whyItMatters":"Delivering siRNA into cells to silence disease genes is a major therapeutic goal. Peptide dendrimers offer advantages over lipid nanoparticles: they are chemically defined, made by solid-phase synthesis from standard building blocks, and easy to modify. Understanding their mechanism through fluorescent tracking helps optimize the design.","specificNumbers":"pH 7.4: tight binding; pH 5.0: release + membrane destabilization; coumarin and BODIPY labels preserved function","methodology":"In vitro study. Peptide dendrimers were synthesized by solid-phase peptide synthesis with coumarin or BODIPY fluorescent labels. siRNA transfection efficiency, binding, aggregation, and secondary structure were compared between labeled and unlabeled versions. FRET was used to track dendrimer-siRNA association in real time. Colocalization microscopy tracked both components during cellular uptake.","limitations":"Tested in cell culture only. The fluorescent labels track mechanism but do not address in vivo challenges like blood stability, biodistribution, and immune clearance. The specific cell types and siRNA targets were not detailed in the abstract. No comparison to established delivery systems like lipid nanoparticles."},{"rthcId":"RPEP-04849","title":"Decoding the proteome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for cell-penetrating peptides involved in pathogenesis or applicable as drug delivery vectors.","authors":"Hemmati, Shiva; Behzadipour, Yasaman; Haddad, Mahdi","year":2020,"journal":"Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases, 85, 104474","doi":"10.1016/j.meegid.2020.104474","pmid":"32712315","tags":["cell-penetrating","peptide-design","infection"],"studyType":"Computational/Bioinformatics","evidenceStrength":"preliminary","keyFinding":"A systematic computational screen of the SARS-CoV-2 proteome identified 310 sequences with cell-penetrating peptide (CPP) characteristics. These SCV2-CPPs spanned regions involved in replication, protein-nucleotide interaction, protein-protein interaction, and complex stabilization.\n\nSafety and practicality analysis: 94.3% were predicted non-toxic. 38% were neither antigenic nor allergenic, important for therapeutic use. 36.7% resisted all four major protease families, meaning they could survive in biological fluids.\n\nStructural analysis: about one-third had sufficient helix or sheet structure for efficient cellular uptake. Among helical CPPs, 44.3% were predicted lipid-binding, important for membrane interaction.\n\nThe top candidates for drug delivery were SCV2-CPP118, 119, 122, and 129, all from NSP12 (RNA-dependent RNA polymerase). Cysteine-rich CPPs from the helicase (NSP13) could potentially form cyclic structures in endosomes for better release.\n\nBeyond delivery: 59.6% had predicted antibacterial activity, 29.6% antiviral, 32.3% antifungal, 63.6% immunomodulatory, and 21.9% anticancer properties.","whyItMatters":"Viruses are nature's experts at getting inside cells. Mining viral proteomes for cell-penetrating peptides converts a pathogen into a source of drug delivery tools. The SARS-CoV-2 proteome had not been screened before. Some identified peptides could serve as delivery vehicles; others might be therapeutic themselves.","specificNumbers":"310 CPPs; 94.3% non-toxic; 38% non-antigenic; 36.7% protease-resistant; 4 top candidates from NSP12","methodology":"Computational study. The entire SARS-CoV-2 proteome was screened using cell-penetrating peptide prediction algorithms. Identified CPPs were analyzed for toxicity, antigenicity, allergenicity, protease resistance, secondary structure, lipid-binding potential, and bioactive properties. Ten experimentally validated viral CPPs from other viruses were used as positive controls to validate the screening pipeline.","limitations":"Entirely computational. None of the 310 peptides have been synthesized or experimentally tested for cell penetration, toxicity, or bioactivity. Prediction algorithms have significant false-positive rates. The four top candidates need laboratory validation. In silico protease resistance predictions do not always match real-world degradation."},{"rthcId":"RPEP-04850","title":"Calcitonin Gene-Related Peptide (CGRP) Antagonists and Their Use in Migraines.","authors":"Henson, Brianna; Hollingsworth, Hanna; Nevois, Erika; Herndon, Chris","year":2020,"journal":"Journal of pain & palliative care pharmacotherapy, 34(1), 22-31","doi":"10.1080/15360288.2019.1690616","pmid":"31763951","tags":["neuropeptides","pain"],"studyType":"Review","evidenceStrength":"strong","keyFinding":"Three FDA-approved CGRP antagonists and four more in clinical development demonstrate consistent efficacy in reducing migraine attacks with favorable safety profiles.","whyItMatters":"Migraine affects millions and current preventive treatments often fail or cause unacceptable side effects. CGRP antagonists offer a targeted, mechanism-based approach with better tolerability.","specificNumbers":"7 CGRP antagonists; 3 approved; positive Phase 3 data; fewer side effects than traditional preventives","methodology":"Review of phase 3 clinical trial data for seven CGRP antagonists, evaluating efficacy and safety outcomes.","limitations":"Review without meta-analysis. Long-term safety data beyond clinical trial durations are still accumulating."},{"rthcId":"RPEP-04851","title":"Moderate Weight Loss Modifies Leptin and Ghrelin Synthesis Rhythms but Not the Subjective Sensations of Appetite in Obesity Patients.","authors":"Hernández Morante, Juan José; Díaz Soler, Inmaculada; Muñoz, Joaquín S Galindo; Sánchez, Horacio Pérez; Barberá Ortega, Mª Del Carmen; Martínez, Carlos Manuel; Morillas Ruiz, Juana Mª","year":2020,"journal":"Nutrients, 12(4)","doi":"10.3390/nu12040916","pmid":"32230732","tags":["weight-loss","hormone-optimization"],"studyType":"Interventional (diet study with controls)","evidenceStrength":"preliminary","keyFinding":"Weight loss produced the expected hormonal changes: leptin (the fullness hormone) decreased overall (P = 0.020 for area under curve and mean level). Ghrelin (the hunger hormone) increased. Both hormones' daily rhythms were modified to more closely resemble those of normal-weight individuals.\n\nThe amount of variability in leptin and ghrelin daily rhythms correlated with diet effectiveness (P < 0.001 for both). People whose hormone rhythms changed more also lost more weight.\n\nThe disconnect: despite these hormonal improvements, subjective appetite sensations (hunger, fullness, desire to eat) barely changed. Patients still felt approximately the same hunger after losing weight as before.\n\nThis confirms that in obesity, the hormonal signals (leptin and ghrelin) cannot properly reach or influence the brain centers that control conscious hunger and satiety. Weight loss partially restores the hormones but does not fix the broken communication.","whyItMatters":"This explains why dieting is so hard. Even when weight loss corrects hormone levels, the brain does not get the message. The hormones are screaming \"you're not hungry\" but the person still feels hungry. Understanding this hormone-brain disconnect is key to developing better obesity treatments.","specificNumbers":"20 obese, 13 controls; 12 weeks; leptin decreased P=0.020; ghrelin increased; rhythm variability correlated with weight loss P<0.001; appetite unchanged","methodology":"Interventional study with 20 obese subjects and 13 normal-weight controls. Obese participants underwent 12 weeks of calorie-restricted diet. Plasma leptin and ghrelin were measured at baseline and end of intervention with multiple time points to capture daily rhythms. Appetite was assessed using validated visual analog scales.","limitations":"Small sample (20 obese, 13 controls). Twelve weeks may not be long enough for appetite regulation to fully adapt. Appetite was measured by self-report, which is subjective. The study measured only leptin and ghrelin; other appetite-regulating hormones (GLP-1, PYY, CCK) were not assessed. No long-term follow-up to see if appetite eventually recalibrates."},{"rthcId":"RPEP-04852","title":"Neutrophil extracellular trap-associated RNA and LL37 enable self-amplifying inflammation in psoriasis.","authors":"Herster, Franziska; Bittner, Zsofia; Archer, Nathan K; Dickhöfer, Sabine; Eisel, David; Eigenbrod, Tatjana; Knorpp, Thomas; Schneiderhan-Marra, Nicole; Löffler, Markus W; Kalbacher, Hubert; Vierbuchen, Tim; Heine, Holger; Miller, Lloyd S; Hartl, Dominik; Freund, Lukas; Schäkel, Knut; Heister, Martin; Ghoreschi, Kamran; Weber, Alexander N R","year":2020,"journal":"Nature communications, 11(1), 105","doi":"10.1038/s41467-019-13756-4","pmid":"31913271","tags":["ll-37","antimicrobial-peptides","inflammation","skin-repair"],"studyType":"Mechanistic (in vitro + in vivo)","evidenceStrength":"strong","keyFinding":"The study overturned a previous assumption. DNA was thought to be the key NET component driving inflammation in psoriasis. Instead, RNA is the critical molecule.\n\nNET-associated RNA (naRNA), when complexed with LL-37, triggered both cytokine release and new NET formation by neutrophils through TLR8 (human) and TLR13 (mouse) receptors. This happened independently of the canonical NET component DNA.\n\nThe self-amplifying mechanism: activated neutrophils release NETs containing RNA. That RNA binds LL-37 (abundant in psoriatic skin). The complex activates more neutrophils to release more NETs with more RNA. Each cycle amplifies the inflammation.\n\nTransferring NETs from activated neutrophils to naive (unstimulated) neutrophils triggered additional NET release, directly demonstrating the self-propagating nature of the cycle.\n\nRNA was abundant in NETs and in psoriatic skin but not in healthy skin. This positions naRNA as a physiologically relevant NET component and a driver of chronic psoriatic inflammation.","whyItMatters":"Psoriasis affects 2-3% of the global population with chronic skin inflammation. LL-37 was already known to be elevated in psoriatic skin. This study reveals the specific mechanism: LL-37 plus NET-derived RNA creates a self-sustaining inflammatory loop. Breaking this cycle could lead to new treatments. Published in Nature Communications, this is a high-impact mechanistic discovery.","specificNumbers":"RNA not DNA is key; TLR8/TLR13 pathway; self-propagating NET cycle; LL-37 as essential partner; Nature Comms","methodology":"Combined in vitro and in vivo study. Primary human and mouse neutrophils were used. NET formation, cytokine release, and TLR activation were measured. TLR8 and TLR13 dependency confirmed using receptor-specific approaches. NET transfer experiments demonstrated self-amplification. In vivo mouse models confirmed RNA-LL37 driven inflammation. RNA abundance compared between psoriatic and healthy skin.","limitations":"Mouse and human TLR systems differ (TLR13 in mice, TLR8 in humans), which adds complexity to translating findings. The self-amplification was demonstrated in vitro and in mouse models, but whether this exact cycle operates in human psoriatic skin in vivo needs confirmation. The study does not show that blocking this pathway reduces psoriasis in a clinical setting."},{"rthcId":"RPEP-04853","title":"Stapled Peptides as HIF-1α/p300 Inhibitors: Helicity Enhancement in the Bound State Increases Inhibitory Potency.","authors":"Hetherington, Kristina; Hegedus, Zsofia; Edwards, Thomas A; Sessions, Richard B; Nelson, Adam; Wilson, Andrew J","year":2020,"journal":"Chemistry (Weinheim an der Bergstrasse, Germany), 26(34), 7638-7646","doi":"10.1002/chem.202000417","pmid":"32307728","tags":["cyclic-peptides","peptide-design","cancer"],"studyType":"Biophysical/Computational","evidenceStrength":"moderate","keyFinding":"The standard assumption in peptide drug design is that stapling peptides into a helix in solution (the unbound state) makes them better drugs because they are pre-organized for binding. This study challenges that assumption.\n\nStapled peptides derived from HIF-1alpha were indeed more potent inhibitors of the HIF-1alpha/p300 protein-protein interaction. But circular dichroism (CD) spectroscopy showed they were not significantly more helical than unstapled versions when free in solution.\n\nMolecular dynamics simulations and CD difference spectra revealed the real mechanism: stapling helped the peptides adopt the bioactive alpha-helical conformation specifically when bound to p300. The staple does not lock the helix beforehand; it enables better helix formation at the moment of binding.\n\nThis finding shifts the design paradigm: optimizing for bound-state helicity, not free-state helicity, is what matters for stapled peptide inhibitors.","whyItMatters":"Protein-protein interactions drive cancer, inflammation, and many diseases but are notoriously hard to drug with small molecules. Stapled peptides are a leading strategy to fill this gap. This study corrects a widespread design assumption, potentially improving how the field creates next-generation stapled peptide drugs.","specificNumbers":"Dibromomaleimide stapling; improved potency; no change in unbound helicity; bound-state helix confirmed by CD and MD","methodology":"Peptides derived from HIF-1alpha were synthesized with and without dibromomaleimide staples. Binding potency was measured using competition assays against the HIF-1alpha/p300 interaction. Circular dichroism characterized secondary structure in unbound and bound states. Molecular dynamics simulations modeled conformational behavior.","limitations":"In vitro study without cellular or animal data. Whether the improved binding potency translates to improved cellular activity is unknown. The dibromomaleimide staple is one of many stapling chemistries; results may differ with other approaches. Molecular dynamics simulations are models, not direct observations."},{"rthcId":"RPEP-04854","title":"Cardiovascular effects of glucagon-like peptide 1 receptor agonists: from mechanistic studies in humans to clinical outcomes.","authors":"Heuvelman, Valerie D; Van Raalte, Daniël H; Smits, Mark M","year":2020,"journal":"Cardiovascular research, 116(5), 916-930","doi":"10.1093/cvr/cvz323","pmid":"31825468","tags":["glp-1","cardiovascular","diabetes"],"studyType":"Review","evidenceStrength":"strong","keyFinding":"The review synthesizes preclinical and clinical evidence for cardiovascular effects of GLP-1 receptor agonists (GLP-1RAs):\n\nGLP-1 receptors are abundantly present in heart tissue, providing a direct mechanism for cardiac effects. Stimulating these receptors affects multiple cardiovascular parameters.\n\nHeart rate increases slightly with GLP-1RAs, typically 2-4 beats per minute. Blood pressure decreases modestly. Both effects are consistent across drugs in the class.\n\nLipid profiles improve: reductions in postprandial triglycerides and total cholesterol. Inflammatory markers decrease, which may contribute to reduced atherosclerosis progression.\n\nMicrovascular function improves in human mechanistic studies, potentially protecting small blood vessels in the heart, kidneys, and other organs.\n\nThese individual effects, taken together, likely explain the reduced rates of heart attacks, strokes, and cardiovascular death seen in landmark trials like LEADER (liraglutide), SUSTAIN-6 (semaglutide), and REWIND (dulaglutide).","whyItMatters":"Heart disease is the leading cause of death in people with type 2 diabetes. GLP-1 drugs reduce cardiovascular events beyond what blood sugar control alone would explain. Understanding the specific cardiovascular mechanisms helps clinicians choose appropriate treatments and helps researchers identify which patients benefit most.","specificNumbers":"415M people with T2DM; GLP-1Rs in heart; HR +2-4bpm; BP reduction; lipid/inflammation improvement; LEADER/SUSTAIN-6/REWIND positive","methodology":"Narrative review of human mechanistic studies measuring GLP-1RA effects on heart rate, blood pressure, microvascular function, lipids, and inflammation. Connects these measured effects to cardiovascular outcome trial results.","limitations":"Narrative review without quantitative meta-analysis. The exact contribution of each mechanism (heart rate, lipids, inflammation, microvascular) to overall cardiovascular benefit is unknown. Some mechanistic data comes from short-term studies that may not reflect chronic treatment effects."},{"rthcId":"RPEP-04855","title":"Role of neutrophils in tuberculosis: A bird's eye view.","authors":"Hilda, J Nancy; Das, Sulochana; Tripathy, Srikanth P; Hanna, Luke Elizabeth","year":2020,"journal":"Innate immunity, 26(4), 240-247","doi":"10.1177/1753425919881176","pmid":"31735099","tags":["antimicrobial-peptides","immune-function","infection","respiratory"],"studyType":"Review","evidenceStrength":"moderate","keyFinding":"Neutrophils kill M. tuberculosis through antimicrobial peptides (alpha-defensins/HNPs), cytokine signaling, and neutrophil extracellular traps, but their excessive activation causes pathological inflammation and tissue damage.","whyItMatters":"Understanding the dual nature of neutrophils in TB could lead to immune-modulating therapies that enhance early antimicrobial peptide-mediated killing while preventing destructive inflammation.","specificNumbers":"HNPs released from granules; NETs trap mycobacteria; IL-8/IL-1β/IFN-γ signaling; excessive response = lung damage","methodology":"Narrative review of published literature on neutrophil functions in tuberculosis infection and immunity.","limitations":"Narrative review without systematic methodology. Research on neutrophil-TB interactions is described as controversial and non-uniform."},{"rthcId":"RPEP-04856","title":"Rational Design of Helix-Stabilized Antimicrobial Peptide Foldamers Containing α,α-Disubstituted Amino Acids or Side-Chain Stapling.","authors":"Hirano, Motoharu; Saito, Chihiro; Goto, Chihiro; Yokoo, Hidetomo; Kawano, Ryuji; Misawa, Takashi; Demizu, Yosuke","year":2020,"journal":"ChemPlusChem, 85(12), 2731-2736","doi":"10.1002/cplu.202000749","pmid":"33369262","tags":["antimicrobial-peptides","peptide-design","infection"],"studyType":"In vitro (peptide design + microbiology)","evidenceStrength":"preliminary","keyFinding":"The rationally designed peptide 'Stripe' was modified using two helix-stabilization strategies: Aib (2-aminoisobutyric acid) incorporation and side-chain stapling.\n\nThe Aib-containing variant was dramatically potent: MIC of 3.125 micromolar against gram-positive S. aureus and an astonishing 1.56 micromolar against a multi-drug resistant Pseudomonas aeruginosa (MDRP) strain. For context, many AMPs require 10-100 micromolar to achieve similar effects.\n\nSafety margin was exceptional: no significant hemolytic activity up to 100+ micromolar, meaning the therapeutic window was at least 64-fold (1.56 vs 100 micromolar).\n\nElectrophysiology experiments explained the selectivity: the peptide formed stable pores in DOPE/DOPG bilayers (mimicking bacterial membranes, which are negatively charged) but not in DOPC bilayers (mimicking mammalian membranes, which are neutral). This charge-based selectivity is why the peptide kills bacteria but not human cells.","whyItMatters":"Multi-drug resistant Pseudomonas aeruginosa is one of the WHO's critical priority pathogens. This peptide kills it at very low concentrations with a wide safety margin. The Aib modification strategy is simple and generalizable, potentially applicable to other antimicrobial peptides to improve their potency.","specificNumbers":"MIC: 1.56µM (MDRP), 3.125µM (S. aureus); no hemolysis >100µM; pores in DOPE/DOPG but not DOPC","methodology":"Peptide chemistry and microbiology study. Stripe-based foldamers were designed computationally, synthesized, and tested for MIC against S. aureus and MDRP. Hemolysis assays measured red blood cell damage. Electrophysiology on model membranes (planar lipid bilayers) characterized pore formation in bacterial-like vs mammalian-like membranes.","limitations":"Tested only against two bacterial species (one gram-positive, one gram-negative). In vitro only; no animal infection models. Pore formation was tested in artificial membranes, not real bacterial cells. Pharmacokinetics (blood stability, distribution, clearance) were not assessed. Cost of Aib-containing peptide synthesis may be higher than standard peptides."},{"rthcId":"RPEP-04857","title":"Cathelicidin preserves intestinal barrier function in polymicrobial sepsis.","authors":"Ho, Jeffery; Chan, Hung; Liang, Yonghao; Liu, Xiaodong; Zhang, Lin; Li, Qing; Zhang, Yuchen; Zeng, Judeng; Ugwu, Felix N; Ho, Idy H T; Hu, Wei; Yau, Johnny C W; Wong, Sunny H; Wong, Wai Tat; Ling, Lowell; Cho, Chi H; Gallo, Richard L; Gin, Tony; Tse, Gary; Yu, Jun; Chan, Matthew T V; Leung, Czarina C H; Wu, William K K","year":2020,"journal":"Critical care (London, England), 24(1), 47","doi":"10.1186/s13054-020-2754-5","pmid":"32041659","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04858","title":"Candidalysin Is a Potent Trigger of Alarmin and Antimicrobial Peptide Release in Epithelial Cells.","authors":"Ho, Jemima; Wickramasinghe, Don N; Nikou, Spyridoula-Angeliki; Hube, Bernhard; Richardson, Jonathan P; Naglik, Julian R","year":2020,"journal":"Cells, 9(3)","doi":"10.3390/cells9030699","pmid":"32178483","tags":["antimicrobial-peptides","immune-function","infection"],"studyType":"In vitro (infection model)","evidenceStrength":"moderate","keyFinding":"Candidalysin, the first cytolytic peptide toxin identified in a human fungal pathogen, triggered release of multiple key immune molecules from epithelial cells:\n\nAlarmins (danger signals) and antimicrobial peptides with known anti-Candida activity were released in response to candidalysin. The specific molecules were not all named in the abstract but include key innate immune effectors.\n\nThe signaling mechanism was novel: extracellular ATP released during candidalysin-mediated cell damage activated EGFR (epidermal growth factor receptor) and MAPK (mitogen-activated protein kinase) signaling cascades. These pathways then drove the downstream antimicrobial peptide and cytokine response.\n\nThis is important because it identifies the exact fungal factor responsible for triggering innate immune defense at mucosal surfaces during oral Candida infection.","whyItMatters":"Candida infections range from oral thrush to life-threatening systemic disease, especially in immunocompromised patients. Understanding how the body first detects Candida through candidalysin-triggered AMP release could lead to therapies that boost this natural defense. It also explains why certain immune deficiencies lead to severe Candida infections.","specificNumbers":"Multiple AMPs and alarmins released; ATP-EGFR-MAPK pathway; candidalysin is first cytolytic fungal toxin; oral epithelial model","methodology":"In vitro study using oral epithelial cell infection models. Cells were exposed to candidalysin and wild-type Candida albicans. Alarmin and AMP release were measured. Signaling pathways (EGFR, MAPK) were characterized using inhibitors and pathway analysis. ATP was measured as a mediator.","limitations":"In vitro study using oral epithelial cells. The specific AMPs and alarmins released were identified but the full panel is best described in the full paper. In vivo confirmation in animal models or human tissue is needed. The role of ATP as a mediator needs further characterization in complex tissue environments."},{"rthcId":"RPEP-04859","title":"Targeting oxytocin receptor (Oxtr)-expressing neurons in the lateral septum to restore social novelty in autism spectrum disorder mouse models.","authors":"Horiai, Machi; Otsuka, Ayano; Hidema, Shizu; Hiraoka, Yuichi; Hayashi, Ryotaro; Miyazaki, Shinji; Furuse, Tamio; Mizukami, Hiroaki; Teruyama, Ryoichi; Tamura, Masaru; Bito, Haruhiko; Maejima, Yuko; Shimomura, Kenju; Nishimori, Katsuhiko","year":2020,"journal":"Scientific reports, 10(1), 22173","doi":"10.1038/s41598-020-79109-0","pmid":"33335150","tags":["oxytocin","neuropeptides","anxiety-mood"],"studyType":"Animal study (mice, neuroscience)","evidenceStrength":"moderate","keyFinding":"Two different autism spectrum disorder (ASD) mouse models were used. One was created by prenatal valproic acid exposure (environmental cause), the other by the Nl3R451C genetic mutation (genetic cause). Both had impaired social memory, the ability to distinguish familiar from novel mice.\n\nSelectively expressing hM3Dq (an activating DREADD receptor) in oxytocin receptor-positive (OXTR+) neurons in the lateral septum (LS) allowed researchers to activate these specific neurons with a chemical trigger.\n\nIn the valproic acid model, activation restored social memory in the three-chamber social test. In the Nl3R451C model, social memory was restored in a single-field test. Both represent core ASD symptoms.\n\nThe OXTR+ neurons in the LS project to the CA1 region of the hippocampus, suggesting social memory depends on an oxytocin-responsive circuit from the lateral septum to the hippocampus. This identifies a specific neural pathway that could explain how intranasal oxytocin therapy improves social symptoms in ASD patients.","whyItMatters":"Oxytocin nasal spray has shown promise in ASD clinical trials, but nobody knew exactly where in the brain it works. This study identifies the lateral septum's OXTR+ neurons as a critical node. Targeting this specific circuit could lead to more precise therapies for the social symptoms of autism.","specificNumbers":"2 ASD models; OXTR+ LS neurons; social memory restored; LS→CA1 projection; DREADDs used","methodology":"Neuroscience study using two mouse models of ASD. DREADDs (designer receptors exclusively activated by designer drugs) were virally expressed in OXTR+ neurons of the lateral septum. Social memory was tested before and after neuron activation. Neural projection mapping confirmed LS-to-CA1 connectivity.","limitations":"Mouse models of autism have limited translational validity. The social behaviors tested are simplified proxies for human social cognition. DREADDs provide proof of concept but are not a practical therapy. The two mouse models represent only a fraction of ASD causes. Whether the LS-CA1 circuit functions the same way in the human brain is unknown."},{"rthcId":"RPEP-04860","title":"Behavioural characterization of ghrelin ligands, anamorelin and HM01: Appetite and reward-motivated effects in rodents.","authors":"Howick, Ken; Chruscicka, Barbara; Felice, Daniela; Ramirez, Valerie T; van Leuven, Lucas; Pietra, Claudio; Cryan, John F; Griffin, Brendan T; Schellekens, Harriët","year":2020,"journal":"Neuropharmacology, 168, 108011","doi":"10.1016/j.neuropharm.2020.108011","pmid":"32067989","tags":["ghrp","weight-loss","receptor-signaling"],"studyType":"In vitro + animal study (rodents)","evidenceStrength":"moderate","keyFinding":"Anamorelin and HM01 are synthetic ghrelin receptor (GHSR-1a) agonists with clinical potential for appetite stimulation. In cellular assays, they showed biased signaling, activating some downstream pathways (calcium mobilization, IP-one) but differing from ghrelin in internalization and beta-arrestin recruitment patterns.\n\nIn rodent feeding studies, both drugs increased food intake, confirming appetite-stimulating effects. However, in reward paradigms (tests measuring motivation to work for food or pleasurable substances), both drugs paradoxically reduced reward-seeking behavior.\n\nBrain c-Fos immunostaining (a marker of neuron activation) revealed divergent activation of central reward circuitry compared to what would be expected from natural ghrelin.\n\nThe key insight: biased signaling matters. These drugs activate the ghrelin receptor differently than natural ghrelin, leading to different behavioral outcomes. For future ghrelin-based therapies, understanding exactly which signaling pathways a drug activates, and whether it reaches reward areas of the brain, will determine success or failure.","whyItMatters":"Ghrelin receptor agonists are being developed for cancer-related wasting (cachexia) and appetite disorders. This study warns that biased signaling can produce unexpected behavioral effects. A drug that increases appetite but reduces food reward motivation may work for cachexia but could have unintended consequences. Understanding signaling bias is essential for designing the right drug for the right condition.","specificNumbers":"Anamorelin and HM01 vs ghrelin; increased food intake; reduced reward behavior; divergent c-Fos brain activation; biased signaling confirmed","methodology":"In vitro cellular assays: calcium mobilization, IP-one accumulation, receptor internalization, and beta-arrestin recruitment comparing anamorelin, HM01, and ghrelin. In vivo rodent studies: food intake measurements, reward-motivated behavior paradigms, and c-Fos brain mapping to identify activated brain regions.","limitations":"Rodent reward behavior may not translate to human experience. The specific reward paradigms chosen may not capture all aspects of food motivation. The paradoxical reduction in reward seeking could reflect the specific behavioral tests used rather than a general effect. Dosing and biodistribution differences between drugs complicate comparison."},{"rthcId":"RPEP-04861","title":"Modulatory effects of BPC 157 on vasomotor tone and the activation of Src-Caveolin-1-endothelial nitric oxide synthase pathway.","authors":"Hsieh, Ming-Jer; Lee, Cheng-Hung; Chueh, Ho-Yen; Chang, Gwo-Jyh; Huang, Hsiu-Yun; Lin, Yuling; Pang, Jong-Hwei S","year":2020,"journal":"Scientific reports, 10(1), 17078","doi":"10.1038/s41598-020-74022-y","pmid":"33051481","tags":["bpc-157","cardiovascular"],"studyType":"In vitro (vascular physiology)","evidenceStrength":"moderate","keyFinding":"BPC-157 produced concentration-dependent vasodilation in isolated rat aorta. The effect was primarily endothelium-dependent: removing the vessel lining nearly eliminated the relaxation, confirming the endothelium is where BPC-157 acts.\n\nThe signaling pathway was mapped step by step:\n1. BPC-157 activates Src kinase (phosphorylation increased)\n2. Activated Src phosphorylates Caveolin-1 (Cav-1)\n3. Phosphorylated Cav-1 releases its inhibitory binding to eNOS\n4. Free eNOS produces nitric oxide (NO)\n5. NO relaxes the smooth muscle in the vessel wall\n\nCo-immunoprecipitation confirmed that BPC-157 reduces the binding between Cav-1 and eNOS, freeing eNOS to work.\n\nBlocking experiments confirmed each step: Src inhibitor abolished the cascade. L-NAME (NO synthase blocker) and hemoglobin (NO scavenger) both prevented vasodilation. Intracellular NO was directly detected using DAF-FM DA fluorescent labeling.\n\nBPC-157 also promoted migration of vascular endothelial cells, consistent with its known angiogenic properties.","whyItMatters":"BPC-157 is one of the most discussed research peptides for tissue repair and healing. This study reveals a specific molecular mechanism for how it works on blood vessels: through the Src-Cav-1-eNOS nitric oxide pathway. Understanding the mechanism helps explain BPC-157's reported wound healing and tissue repair properties, since nitric oxide and angiogenesis are key to healing.","specificNumbers":"Concentration-dependent vasodilation; endothelium-dependent; Src→Cav-1→eNOS→NO pathway; co-IP confirmed reduced Cav-1/eNOS binding","methodology":"In vitro vascular physiology study. Isolated rat aortic rings were tested in organ bath experiments with and without endothelium. Signaling pathway components (Src, Cav-1, eNOS phosphorylation) measured by Western blot. Protein-protein binding assessed by co-immunoprecipitation. NO production measured by fluorescent DAF-FM DA labeling. Endothelial cell migration assays performed. 3D vascular smooth muscle cell models used to assess direct smooth muscle effects.","limitations":"Tested in isolated rat aorta, not in living animals or humans. Organ bath experiments use supraphysiological conditions. The endothelium-independent effects at high concentrations were noted but not fully explained. No dose-response data from in vivo administration. The clinical relevance of these findings to human BPC-157 use is unknown, as human studies are virtually non-existent."},{"rthcId":"RPEP-04862","title":"HLA class I restricted epitopes prediction of common tumor antigens in white and East Asian populations: Implication on antigen selection for cancer vaccine design.","authors":"Hu, Wei; He, Meifang; Li, Liangping","year":2020,"journal":"PloS one, 15(2), e0229327","doi":"10.1371/journal.pone.0229327","pmid":"32106223","tags":["cancer","peptide-design"],"studyType":"Computational immunology","evidenceStrength":"preliminary","keyFinding":"The study analyzed 6 cancer-testis antigens (CTAs) and 95 common cancer mutations for their ability to produce peptides that bind HLA class I molecules in two populations.\n\nFor CTAs, the overall epitope prediction difference between white and East Asian populations was small. There was a linear relationship between peptide length and epitope occurrence, meaning longer fragments produced more potential targets.\n\nFor mutation-derived neoantigens (from missense mutations), population differences were larger, reflecting different HLA allele distributions.\n\nThe most striking finding: mutations with the highest incidence in cancer patients had the lowest predicted epitope occurrence. Conversely, rare mutations had the most immune-visible peptides. This inverse relationship suggests immunosurveillance: the immune system kills tumors with easily detectable mutations, so only mutations that evade immunity become common.\n\nFrameshift/indel mutations fell between CTAs and point mutations in the peptide length-epitope relationship.","whyItMatters":"Cancer vaccines need to target peptides that the patient's immune system can actually recognize. This study shows population-specific HLA differences matter more for neoantigen vaccines than for CTA vaccines. The finding that common mutations are immunologically invisible explains a major challenge in cancer immunotherapy and guides target selection.","specificNumbers":"6 CTAs; 95 mutations; inverse mutation incidence/epitope relationship; small CTA population differences; larger neoantigen differences","methodology":"Computational immunology study. Six CTAs commonly used in immunotherapy and 95 hotspot mutations from The Cancer Genome Atlas were analyzed. HLA class I binding affinity was predicted for the most common alleles in white and East Asian populations. Epitope occurrence was correlated with mutation incidence.","limitations":"Entirely computational. Predicted binding does not guarantee immunogenicity (actual immune response). HLA binding is necessary but not sufficient for T cell activation. The analysis used common HLA alleles, which do not cover all patients. Real-world cancer vaccine efficacy depends on many factors beyond HLA binding."},{"rthcId":"RPEP-04863","title":"Beneficial effect of probiotics on Pseudomonas aeruginosa-infected intestinal epithelial cells through inflammatory IL-8 and antimicrobial peptide human beta-defensin-2 modulation.","authors":"Huang, Fu-Chen; Lu, Yi-Ting; Liao, Yu-Hsuan","year":2020,"journal":"Innate immunity, 26(7), 592-600","doi":"10.1177/1753425920959410","pmid":"32988256","tags":["antimicrobial-peptides","gut-healing","immune-function","infection"],"studyType":"In vitro (infection model)","evidenceStrength":"preliminary","keyFinding":"Two probiotic strains (Lactobacillus rhamnosus GG and Bifidobacterium longum spp. infantis S12) produced a dual effect when administered to intestinal epithelial cells (SW480) before Pseudomonas aeruginosa infection:\n\nhBD-2 was enhanced: probiotic pretreatment increased both mRNA expression and secreted protein of this antimicrobial peptide, strengthening the direct antimicrobial defense.\n\nIL-8 was suppressed: the inflammatory chemokine IL-8 was reduced, meaning less inflammatory immune cell recruitment and less tissue damage.\n\nThe mechanism: probiotics enhanced P. aeruginosa-induced membranous NOD1 protein expression and Akt activation. When Akt or NOD1 were knocked down with siRNA, the probiotic effects on IL-8 and hBD-2 were both reversed. This confirms NOD1 and Akt are the regulatory nodes.\n\nThis reciprocal regulation (more antimicrobial defense, less inflammation) is the ideal immune response: kill the pathogen without destroying the tissue.","whyItMatters":"Pseudomonas aeruginosa can cause fatal sepsis, especially in young children. Antibiotics are the standard treatment but overuse drives resistance. Probiotics offer a complementary approach by boosting the body's own antimicrobial peptides while reducing the damaging inflammation that worsens disease. This dual action is more targeted than broad-spectrum antibiotics.","specificNumbers":"2 probiotic strains; hBD-2 up, IL-8 down; NOD1 and Akt confirmed; siRNA knockdown reversed effects","methodology":"In vitro cell culture study using SW480 intestinal epithelial cells. Cells were pretreated with probiotics, then infected with PAO1 Pseudomonas aeruginosa. IL-8 and hBD-2 measured at mRNA and protein levels. Akt and NOD1 signaling assessed. siRNA knockdown of Akt and NOD1 confirmed their roles.","limitations":"In vitro only, using a single intestinal cell line (SW480). Real intestinal tissue has multiple cell types, a mucus layer, and commensal bacteria that could modify the response. The probiotics were given before infection (pretreatment), not during; whether they work after infection starts is unknown. Only one Pseudomonas strain was tested."},{"rthcId":"RPEP-04864","title":"Immunopotentiator thymosin alpha-1 attenuates inflammatory pain by modulating the Wnt3a/β-catenin pathway in spinal cord.","authors":"Huang, Jiahua; Jiang, Huaqing; Pan, Meijun; Jiang, Yanjun; Xie, Lijin","year":2020,"journal":"Neuroreport, 31(1), 69-75","doi":"10.1097/WNR.0000000000001370","pmid":"31764244","tags":["thymosin-alpha-1","pain","inflammation"],"studyType":"Animal study (rats)","evidenceStrength":"preliminary","keyFinding":"Complete Freund's adjuvant (CFA) injection created inflammatory pain in rats, causing both mechanical allodynia (pain from normally non-painful touch) and heat hyperalgesia (increased heat sensitivity). Thymosin alpha-1 (Ta1) reduced both types of pain.\n\nTa1 lowered CFA-induced inflammatory mediators in the spinal cord: IFN-gamma, TNF-alpha, and brain-derived neurotrophic factor (BDNF) were all suppressed.\n\nThe Wnt3a/beta-catenin pathway, which was activated in the spinal cord after CFA injection in parallel with pain hypersensitivity, was reversed by Ta1 treatment. This pathway is increasingly recognized as a driver of chronic pain through its role in spinal cord neuroinflammation.\n\nThe combination of anti-inflammatory and Wnt pathway modulation provides a dual mechanism for Ta1's pain-reducing effects.","whyItMatters":"Thymosin alpha-1 is an FDA-approved immune modulator (Zadaxin) used for hepatitis and as a cancer adjuvant. Discovering it also reduces inflammatory pain through a novel mechanism (Wnt pathway) opens a potential new application. Current pain treatments often have addiction risks (opioids) or limited efficacy (NSAIDs). An immune-based approach could be safer.","specificNumbers":"Reduced allodynia and hyperalgesia; suppressed IFN-γ, TNF-α, BDNF; Wnt3a/β-catenin pathway reversed","methodology":"Animal study in rats. CFA was injected to induce inflammatory pain. Mechanical allodynia and heat hyperalgesia were measured as pain outcomes. Spinal cord tissue was analyzed for inflammatory mediators and Wnt3a/beta-catenin pathway components.","limitations":"Tested in rats, not humans. The CFA model is acute inflammatory pain; results may differ in chronic pain conditions. The exact mechanism connecting Ta1 to Wnt pathway suppression was not fully elucidated. Dosing and timing details were limited in the abstract. Pain was measured by behavioral tests, which are less precise than electrophysiology."},{"rthcId":"RPEP-04865","title":"Generation of Marker-Free pbd-2 Knock-in Pigs Using the CRISPR/Cas9 and Cre/loxP Systems.","authors":"Huang, Jing; Wang, Antian; Huang, Chao; Sun, Yufan; Song, Bingxiao; Zhou, Rui; Li, Lu","year":2020,"journal":"Genes, 11(8)","doi":"10.3390/genes11080951","pmid":"32824735","tags":["antimicrobial-peptides","peptide-design"],"studyType":"Genetic engineering (proof-of-concept)","evidenceStrength":"preliminary","keyFinding":"Two copies of the pbd-2 gene linked by a T2A sequence were inserted into the porcine Rosa26 locus (a safe harbor site) using CRISPR/Cas9. The neomycin resistance marker was removed by cell-penetrating Cre recombinase with 48.3% efficiency, creating marker-free cells.\n\nCloned piglets were produced via somatic cell nuclear transfer. PCR and Southern blot confirmed correct gene insertion. Immunohistochemistry and immunofluorescence showed significantly higher PBD-2 protein across different tissues of transgenic piglets compared to wild-type littermates.\n\nFunctional testing was critical: cell culture supernatants from transgenic pig ear fibroblasts killed bacteria significantly more effectively than wild-type controls, confirming the extra PBD-2 is biologically active.","whyItMatters":"Pig farming loses billions annually to infectious disease. Porcine beta-defensin 2 has antimicrobial, immunomodulatory, and growth-promoting properties. Creating pigs that naturally produce more of this defense peptide could reduce antibiotic use in agriculture, a major driver of antibiotic resistance.","specificNumbers":"2 pbd-2 copies; Rosa26 locus; 48.3% Cre efficiency; higher PBD-2 in all tissues; enhanced bactericidal activity","methodology":"Genetic engineering study. CRISPR/Cas9 was used for targeted gene knock-in at the Rosa26 locus. Cre/loxP system removed the selection marker. Somatic cell nuclear transfer produced cloned piglets. Gene integration confirmed by PCR and Southern blot. Protein expression measured by immunohistochemistry and immunofluorescence. Antimicrobial function tested by bactericidal assays on cell culture supernatants.","limitations":"Small number of cloned piglets produced. Long-term health, growth performance, and actual disease resistance in farm conditions were not tested. Somatic cell nuclear transfer has high failure rates and ethical concerns. Regulatory approval for gene-edited food animals varies by country. The specific bacteria used in the bactericidal assay were not named in the abstract."},{"rthcId":"RPEP-04866","title":"Peptidoglycan derived from Lactobacillus rhamnosus MLGA up-regulates the expression of chicken β-defensin 9 without triggering an inflammatory response.","authors":"Huang, Juan; Li, Junhui; Li, Qiufen; Li, Lin; Zhu, Nianhua; Xiong, Xiaowen; Li, Guanhong","year":2020,"journal":"Innate immunity, 26(8), 733-745","doi":"10.1177/1753425920949917","pmid":"32847443","tags":["antimicrobial-peptides","immune-function","gut-healing"],"studyType":"In vitro / ex vivo","evidenceStrength":"moderate","keyFinding":"Peptidoglycan from probiotic L. rhamnosus MLGA produced a dose-dependent increase in avian beta-defensin 9 (AvBD9) mRNA in multiple immune cell types (PBMCs, splenocytes, thymocytes, hepatocytes) and in chicken embryo intestinal explants (jejunum, ileum, cecum).\n\nFunctional validation: lysates from peptidoglycan-treated PBMCs and splenocytes showed increased ability to inhibit Salmonella Enteritidis growth, confirming the induced defensin was biologically active.\n\nCritically, this defensin induction occurred without activating pro-inflammatory cytokines IL-1beta, IL-8, and IL-12p40. When peptidoglycan was digested with lysozyme, the hydrolysate actually suppressed these inflammatory cytokines.\n\nIn contrast, peptidoglycan from pathogenic S. aureus reduced AvBD9 expression in PBMCs and splenocytes, showing pathogen-derived vs probiotic-derived cell wall material has opposite effects on defensin production.","whyItMatters":"Antibiotics in poultry farming drive resistance. Probiotics can enhance natural defense, but the mechanism was unclear. This study shows a specific probiotic component (peptidoglycan) boosts antimicrobial peptide production without causing harmful inflammation. This precision is ideal: kill pathogens without damaging the gut.","specificNumbers":"AvBD9 up in all cell types; Salmonella killing enhanced; no IL-1β/IL-8/IL-12p40; S. aureus PG had opposite effect","methodology":"In vitro and ex vivo study using chicken immune cells and embryonic intestinal explants. Peptidoglycan was purified from L. rhamnosus MLGA and S. aureus. AvBD9 expression measured by qPCR. Antimicrobial function tested by Salmonella growth inhibition assays. Cytokine expression (IL-1beta, IL-8, IL-12p40) monitored to assess inflammatory response.","limitations":"Tested in chicken cells and embryonic explants, not in live chickens challenged with pathogens. The specific structural features of probiotic vs pathogenic peptidoglycan that explain their opposite effects were not identified. Only one probiotic species and one pathogen were compared. The dose-response relationship in live birds may differ from cell culture."},{"rthcId":"RPEP-04867","title":"pVACtools: A Computational Toolkit to Identify and Visualize Cancer Neoantigens.","authors":"Hundal, Jasreet; Kiwala, Susanna; McMichael, Joshua; Miller, Christopher A; Xia, Huiming; Wollam, Alexander T; Liu, Connor J; Zhao, Sidi; Feng, Yang-Yang; Graubert, Aaron P; Wollam, Amber Z; Neichin, Jonas; Neveau, Megan; Walker, Jason; Gillanders, William E; Mardis, Elaine R; Griffith, Obi L; Griffith, Malachi","year":2020,"journal":"Cancer immunology research, 8(3), 409-420","doi":"10.1158/2326-6066.CIR-19-0401","pmid":"31907209","tags":["cancer","peptide-design"],"studyType":"Software/Methods","evidenceStrength":"strong","keyFinding":"pVACtools provides an end-to-end pipeline for personalized cancer vaccine design with several key modules:\n\npVACseq predicts neoantigens from point mutations, insertions, deletions, and gene fusions. It supports an ensemble of MHC binding prediction algorithms for both Class I and Class II, making predictions more robust than single-algorithm approaches.\n\nPrioritization integrates multiple data types: mutant allele expression level (is the mutation actually producing protein?), binding affinity to the patient's HLA types, and whether the mutation is clonal (present in all tumor cells) or subclonal.\n\npVACviz provides a web-based graphical interface for clinical teams to review, interpret, and select candidates.\n\npVACvector optimizes peptide ordering to minimize junctional epitopes (unintended immune targets created where peptides join) in DNA vector vaccines.\n\nAdditional modules assess synthetic long peptide vaccine candidates for manufacturability factors like solubility and synthesis feasibility.","whyItMatters":"Personalized cancer vaccines require identifying which mutations in each patient's tumor will produce the best immune targets. This is computationally complex. pVACtools automates the process, making personalized vaccine design accessible to clinical teams. It is freely available and has been widely adopted in the cancer immunotherapy research community.","specificNumbers":"MHC I+II binding; mutations/indels/fusions; expression+clonality prioritization; web UI; DNA vector and SLP modules","methodology":"Software development paper. The pipeline was built using established genomics tools and integrates multiple MHC binding prediction algorithms. Modules handle different vaccine delivery approaches (DNA vectors, synthetic long peptides). Validation was performed using test datasets.","limitations":"Neoantigen prediction remains imperfect. Not all predicted binders actually generate immune responses. The tool predicts binding but cannot fully predict immunogenicity (whether T cells will actually respond). Manufacturing challenges for personalized vaccines are not fully addressed by the software. Computation time can be significant for large tumor mutation loads."},{"rthcId":"RPEP-04868","title":"Effects of semaglutide on risk of cardiovascular events across a continuum of cardiovascular risk: combined post hoc analysis of the SUSTAIN and PIONEER trials.","authors":"Husain, Mansoor; Bain, Stephen C; Holst, Anders Gaarsdal; Mark, Thomas; Rasmussen, Søren; Lingvay, Ildiko","year":2020,"journal":"Cardiovascular diabetology, 19(1), 156","doi":"10.1186/s12933-020-01106-4","pmid":"32998732","tags":["semaglutide","cardiovascular","diabetes"],"studyType":"Post hoc analysis of Phase 3 clinical trials","evidenceStrength":"strong","keyFinding":"Prior cardiovascular outcome trials showed semaglutide reduced MACE (major adverse cardiovascular events: CV death, non-fatal stroke, non-fatal MI) in high-risk patients. This post hoc analysis asked: does the benefit extend to lower-risk patients?\n\nA cardiovascular risk prediction model was developed from LEADER trial data and validated on the semaglutide dataset (area under the curve: 0.77, indicating good predictive performance).\n\nKey finding: semaglutide reduced both relative and absolute risk of MACE versus comparators across the entire continuum of cardiovascular risk. The relative risk reduction tended to be largest in patients with low CV risk scores. The absolute risk reduction was largest for intermediate to high risk scores (because these patients had more events to prevent).\n\nPrevious data: SUSTAIN-6 showed HR 0.74 [0.58-0.95] for injectable semaglutide vs placebo. PIONEER 6 showed HR 0.79 [0.57-1.11] for oral semaglutide vs placebo. This analysis extends those findings across the risk spectrum.\n\nSimilar patterns were seen for individual MACE components and when only placebo comparator data were included.","whyItMatters":"This is important for prescribing decisions. If semaglutide only protected high-risk patients, it would only be indicated for that group. Showing benefit across all risk levels supports broader use in type 2 diabetes, including patients without established cardiovascular disease.","specificNumbers":"SUSTAIN-6 HR 0.74; PIONEER 6 HR 0.79; CV risk model AUC 0.77; benefit across entire risk continuum","methodology":"Post hoc analysis combining individual patient-level data from SUSTAIN and PIONEER phase 3a clinical programs. Time-to-first-MACE analyzed by treatment assignment. CV risk model developed from independent LEADER trial data. Risk model applied to predict baseline CV risk in the semaglutide dataset, then treatment effects analyzed as a function of predicted risk.","limitations":"Post hoc analysis, not a pre-specified trial outcome. The CV risk model was developed from LEADER (liraglutide) data and applied to semaglutide data; model transferability is assumed but not guaranteed. Individual trials were not powered for subgroup analyses by risk level. Combining data across trials with different comparators introduces heterogeneity."},{"rthcId":"RPEP-04869","title":"Semaglutide (SUSTAIN and PIONEER) reduces cardiovascular events in type 2 diabetes across varying cardiovascular risk.","authors":"Husain, Mansoor; Bain, Stephen C; Jeppesen, Ole K; Lingvay, Ildiko; Sørrig, Rasmus; Treppendahl, Marianne B; Vilsbøll, Tina","year":2020,"journal":"Diabetes, obesity & metabolism, 22(3), 442-451","doi":"10.1111/dom.13955","pmid":"31903692","tags":["semaglutide","cardiovascular","diabetes"],"studyType":"Pooled post hoc analysis of cardiovascular outcome trials","evidenceStrength":"strong","keyFinding":"Combining individual patient-level data from SUSTAIN 6 (injectable semaglutide) and PIONEER 6 (oral semaglutide) versus placebo:\n\nOverall MACE: HR 0.76 (95% CI 0.62-0.92), a 24% reduction. This was statistically significant.\n\nIndividual components: non-fatal stroke showed the strongest effect at HR 0.65 (95% CI 0.43-0.97), a 35% reduction. CV death and non-fatal MI showed numerical reductions but individual confidence intervals were wider.\n\nHeart failure hospitalization: HR 1.03 (95% CI 0.75-1.40), no benefit. Notably, patients with prior heart failure also showed no MACE benefit (interaction P = 0.046).\n\nSubgroup analyses: consistent MACE reduction in patients with and without established CV disease or chronic kidney disease, and in patients with and without prior MI or stroke (all interaction P > 0.05 except HF).\n\nIn the combined glycemic efficacy trials (where comparators included active drugs, not just placebo), MACE HR was 0.85 (95% CI 0.55-1.33).","whyItMatters":"This pooled analysis provides the strongest cardiovascular evidence for semaglutide from its dedicated outcome trials. The 24% MACE reduction and particularly the 35% stroke reduction support semaglutide as a cardiovascular protective drug, not just a glucose-lowering agent. The lack of heart failure benefit is clinically important for patient selection.","specificNumbers":"MACE HR 0.76 (0.62-0.92); stroke HR 0.65 (0.43-0.97); HF HR 1.03 (no benefit); consistent across subgroups except prior HF","methodology":"Pre-specified post hoc analysis combining individual patient-level data from two cardiovascular outcome trials: SUSTAIN 6 (n=3,297) and PIONEER 6 (n=3,183). Cox proportional hazards models for time-to-first MACE and components. Subgroup analyses by baseline CV risk factors.","limitations":"Post hoc combined analysis. The two trials had different designs (SUSTAIN 6 was longer). Subgroup analyses, while consistent, have reduced statistical power. The heart failure null finding is based on a relatively small number of events. The glycemic efficacy trial analysis was underpowered for CV endpoints."},{"rthcId":"RPEP-04870","title":"Structure-Based Design, Synthesis and Bioactivity of a New Anti-TNFα Cyclopeptide.","authors":"Idress, Mohannad; Milne, Bruce F; Thompson, Gary S; Trembleau, Laurent; Jaspars, Marcel; Houssen, Wael E","year":2020,"journal":"Molecules (Basel, Switzerland), 25(4)","doi":"10.3390/molecules25040922","pmid":"32093030","tags":["cyclic-peptides","inflammation","peptide-design"],"studyType":"Computational design + in vitro validation","evidenceStrength":"preliminary","keyFinding":"A computationally designed cyclopeptide successfully inhibits the TNFα-TNFR1 protein-protein interaction, validated by NMR structural analysis and biological activity assays.","whyItMatters":"TNFα inhibitors are among the most prescribed biologics worldwide but are expensive antibodies. A cyclopeptide alternative could offer a cheaper, more stable option for treating inflammatory diseases.","specificNumbers":"NMR solution structure; computational design; TNF-alpha/TNFR-1 target; activity confirmed in sensor cells","methodology":"Conformational analysis and molecular docking for design, solution-state NMR for structural confirmation, TNFα sensor cells for biological activity validation.","limitations":"In vitro validation only. Biological activity assessed using sensor cells, not disease models. Pharmacokinetic properties and in vivo efficacy unknown."},{"rthcId":"RPEP-04871","title":"Exenatide induces frataxin expression and improves mitochondrial function in Friedreich ataxia.","authors":"Igoillo-Esteve, Mariana; Oliveira, Ana F; Cosentino, Cristina; Fantuzzi, Federica; Demarez, Céline; Toivonen, Sanna; Hu, Amélie; Chintawar, Satyan; Lopes, Miguel; Pachera, Nathalie; Cai, Ying; Abdulkarim, Baroj; Rai, Myriam; Marselli, Lorella; Marchetti, Piero; Tariq, Mohammad; Jonas, Jean-Christophe; Boscolo, Marina; Pandolfo, Massimo; Eizirik, Décio L; Cnop, Miriam","year":2020,"journal":"JCI insight, 5(2)","doi":"10.1172/jci.insight.134221","pmid":"31877117","tags":["exenatide","glp-1","neuroprotection"],"studyType":"Translational (mouse + iPSC + pilot human trial)","evidenceStrength":"moderate","keyFinding":"The study tested exenatide across three levels of evidence:\n\nIn frataxin-deficient mice, exenatide improved glucose handling through enhanced insulin content and secretion. More importantly, it induced frataxin protein and iron-sulfur cluster-containing proteins in both pancreatic beta cells and brain tissue. It was also protective to sensory neurons in dorsal root ganglia, the neurons that die in Friedreich ataxia.\n\nIn patient-derived induced pluripotent stem cells (iPSCs) differentiated into beta cells and sensory neurons, GLP-1 analogs induced frataxin expression, reduced oxidative stress, and improved mitochondrial function.\n\nIn a pilot human trial, Friedreich ataxia patients treated with exenatide for 5 weeks showed modest frataxin induction in platelets. While modest, this is the first demonstration that a GLP-1 drug can increase frataxin in actual patients.\n\nThe mechanism involves GLP-1 receptor (incretin receptor) activation, identifying this receptor as a new therapeutic target for Friedreich ataxia.","whyItMatters":"Friedreich ataxia has no treatment to slow disease progression. It affects about 1 in 50,000 people and causes progressive loss of coordination, heart disease, and diabetes. Finding that an already-approved drug (exenatide) can increase the deficient protein (frataxin) and improve the fundamental cellular defect (mitochondrial dysfunction) is a significant breakthrough that could lead to clinical trials.","specificNumbers":"Frataxin induced in brain and beta cells; oxidative stress reduced in iPSC neurons; modest platelet frataxin increase in 5-week pilot; JCI Insight","methodology":"Multi-level study: frataxin-deficient mouse models (in vivo), patient iPSC-derived beta cells and sensory neurons (in vitro), and a pilot clinical trial in Friedreich ataxia patients (5 weeks of exenatide treatment with platelet frataxin measurements). Published in JCI Insight.","limitations":"The pilot trial was very small and short (5 weeks). Platelet frataxin is a surrogate marker that may not reflect brain frataxin levels. The frataxin induction in patients was described as \"modest.\" Mouse models of Friedreich ataxia do not perfectly replicate human disease. Whether the frataxin increase is sufficient to slow neurodegeneration is unknown."},{"rthcId":"RPEP-04872","title":"Chiral Cyclobutane-Containing Cell-Penetrating Peptides as Selective Vectors for Anti-Leishmania Drug Delivery Systems.","authors":"Illa, Ona; Olivares, José-Antonio; Gaztelumendi, Nerea; Martínez-Castro, Laura; Ospina, Jimena; Abengozar, María-Ángeles; Sciortino, Giuseppe; Maréchal, Jean-Didier; Nogués, Carme; Royo, Míriam; Rivas, Luis; Ortuño, Rosa M","year":2020,"journal":"International journal of molecular sciences, 21(20)","doi":"10.3390/ijms21207502","pmid":"33053805","tags":["cell-penetrating","cyclic-peptides","infection"],"studyType":"In vitro (peptide design + parasitology)","evidenceStrength":"preliminary","keyFinding":"Two series of hybrid gamma/gamma-peptides (gamma-CC and gamma-CT) were designed using a chiral cyclobutane amino acid alternating with proline derivatives. Key findings:\n\nSelectivity: both peptide series showed no cytotoxicity to human HeLa cells and only moderate uptake by these cells. In contrast, both 14-mer versions were microbicidal against Leishmania at concentrations above 25 micromolar, with significant intracellular accumulation in the parasite.\n\nDrug delivery: when conjugated to fluorescent doxorubicin (Dox), the peptides showed toxicity to Leishmania above 1 micromolar, while free Dox at the same concentration was not toxic. Intracellular accumulation was 2.5 times higher than with a Dox-TAT conjugate (TAT being the standard cell-penetrating peptide).\n\nStructural insight: computational calculations showed the drug-peptide conjugates fold to bury the Dox moiety inside a cavity while exposing positively charged groups to solvent. This improves Dox solubility and membrane translocation.","whyItMatters":"Leishmaniasis affects 12 million people and kills 20,000-30,000 annually. Current drugs are toxic and losing effectiveness. A delivery system that selectively targets the parasite while sparing human cells could transform treatment. The 2.5-fold improvement over TAT peptide delivery is significant.","specificNumbers":"Non-toxic to HeLa; killing >25µM; Dox conjugate >1µM; 2.5x vs TAT accumulation; 14-mer optimal","methodology":"Peptide chemistry and parasitology study. Hybrid gamma-peptides were synthesized and tested for cytotoxicity (HeLa cells), parasite killing (Leishmania), and intracellular accumulation. Doxorubicin conjugates were prepared and compared to free Dox and Dox-TAT. Conformational analysis by circular dichroism and molecular dynamics simulations.","limitations":"Tested only in cell culture, not in animal infection models. The selectivity mechanism (why parasites take up the peptide more than human cells) is not fully explained. Only one drug (doxorubicin) was tested as cargo. The 25 micromolar killing concentration for the peptide alone is relatively high. Long-term stability and in vivo biodistribution are unknown."},{"rthcId":"RPEP-04873","title":"Peptides Derived from (RRWQWRMKKLG)2-K-Ahx Induce Selective Cellular Death in Breast Cancer Cell Lines through Apoptotic Pathway.","authors":"Insuasty-Cepeda, Diego Sebastián; Barragán-Cárdenas, Andrea Carolina; Ochoa-Zarzosa, Alejandra; López-Meza, Joel E; Fierro-Medina, Ricardo; García-Castañeda, Javier Eduardo; Rivera-Monroy, Zuly Jenny","year":2020,"journal":"International journal of molecular sciences, 21(12)","doi":"10.3390/ijms21124550","pmid":"32604743","tags":["antimicrobial-peptides","cancer"],"studyType":"In vitro (peptide design + cancer biology)","evidenceStrength":"preliminary","keyFinding":"The parent peptide LfcinB(20-30)2 is a dimeric version of a bovine lactoferricin fragment. Researchers systematically replaced the Met-26 residue with amino acids of varying polarity.\n\nKey finding: hydrophobic substitutions dramatically enhanced cancer cell killing. IC50 values reached as low as 6 micromolar against both HTB-132 and MCF-7 breast cancer cell lines. Less hydrophobic or polar substitutions were less effective.\n\nSelectivity: the modified peptides showed significantly lower cytotoxicity to MCF-12 non-tumorigenic breast cells, demonstrating cancer-cell selectivity.\n\nSpeed: the cytotoxic effect was remarkably fast, appearing within just 90 minutes and persisting for up to 48 hours.\n\nMechanism: flow cytometry confirmed death through apoptosis (programmed cell death), not necrosis. The cell membrane remained intact, ruling out a simple membrane-lytic mechanism. Intrinsic apoptotic pathway markers were detected.\n\nThis suggests these peptides trigger an internal death program in cancer cells rather than just punching holes in membranes.","whyItMatters":"Breast cancer is the most common cancer in women. These peptides kill breast cancer cells selectively, rapidly, and through apoptosis. The structure-activity relationship is clear: hydrophobicity at position 26 drives potency. This provides a rational design path for improved anticancer peptides.","specificNumbers":"IC50 ~6µM; selective vs MCF-12; killing at 90 min; apoptosis confirmed; membrane intact; Met→hydrophobic key","methodology":"Peptide synthesis and cancer cell biology study. Dimeric lactoferricin analog peptides synthesized with Met-26 substitutions. Cytotoxicity tested on HTB-132 (breast cancer), MCF-7 (breast cancer), and MCF-12 (non-tumorigenic) cell lines. Cell death mechanism analyzed by flow cytometry (apoptosis vs necrosis, membrane integrity). Time-course experiments tracked killing kinetics.","limitations":"Tested only in cell culture, not in animals or humans. Only two breast cancer cell lines and one non-cancerous line were tested. The selectivity ratio (cancer vs normal) is not quantified in the abstract. The dimeric peptide structure may present manufacturing challenges for clinical development. In vivo pharmacokinetics and stability are unknown."},{"rthcId":"RPEP-04874","title":"Metabolic and cardiovascular benefits of GLP-1 agonists, besides the hypoglycemic effect (Review).","authors":"Iorga, Roua Anamaria; Bacalbasa, Nicolae; Carsote, Mara; Bratu, Ovidiu Gabriel; Stanescu, Ana Maria Alexandra; Bungau, Simona; Pantis, Carmen; Diaconu, Camelia Cristina","year":2020,"journal":"Experimental and therapeutic medicine, 20(3), 2396-2400","doi":"10.3892/etm.2020.8714","pmid":"32765722","tags":["glp-1","cardiovascular","diabetes","weight-loss"],"studyType":"Review","evidenceStrength":"strong","keyFinding":"The review covers multiple GLP-1 receptor agonists and their non-glycemic benefits:\n\nCardiovascular events: semaglutide and liraglutide demonstrated significant reduction in MACE with similar cardiovascular mortality rates. GLP-1RA use was associated with reduced cardiovascular and all-cause mortality versus placebo.\n\nSafety: no increased risk of pancreatitis or thyroid cancer compared to placebo, addressing two common safety concerns.\n\nBlood pressure and weight: exenatide and liraglutide decreased blood pressure values and body weight, and improved dyslipidemia.\n\nVascular biology: liraglutide specifically improved blood circulation by increasing nitric oxide levels and inhibiting adhesion molecules and procoagulant factors, both in lab experiments and clinical settings.\n\nCardiac remodeling: liraglutide showed beneficial effects on cardiac remodeling after heart attack in animal models, though more large trials were needed.\n\nGuideline impact: international guidelines now recommend GLP-1RAs as first-line therapy in type 2 diabetes patients with high cardiovascular risk or as first-line in metformin-intolerant patients.","whyItMatters":"Type 2 diabetes patients have 2-4 times higher cardiovascular risk than the general population. GLP-1 drugs address this directly through multiple mechanisms beyond blood sugar: weight loss, blood pressure reduction, improved lipids, reduced inflammation, and direct vascular protection. This multi-pronged benefit is unique among diabetes drug classes.","specificNumbers":"Semaglutide/liraglutide: reduced MACE; safe pancreatitis/thyroid; BP and weight reduction; NO increase; first-line guideline recommendation","methodology":"Narrative review of clinical trials, mechanistic studies, and guideline recommendations for GLP-1 receptor agonists in type 2 diabetes.","limitations":"Narrative review without systematic search or meta-analysis. Some benefits (like cardiac remodeling) were supported only by animal data. Long-term safety data beyond 3-5 years was limited. Head-to-head comparisons between GLP-1 drugs were not available."},{"rthcId":"RPEP-04875","title":"Sequence-Dependent Bioactivity and Self-Assembling Properties of RGD-Containing Amphiphilic Peptides as Extracellular Scaffolds.","authors":"Ishida, Atsuya; Oshikawa, Mio; Ajioka, Itsuki; Muraoka, Takahiro","year":2020,"journal":"ACS applied bio materials, 3(6), 3605-3611","doi":"10.1021/acsabm.0c00240","pmid":"35025230","tags":["peptide-design","bioavailability"],"studyType":"Biomaterials (in vitro)","evidenceStrength":"moderate","keyFinding":"All variants had identical amino acid composition (same letters, different order), yet behaved very differently:\n\nA6G: RGD at this position disrupted beta-sheet formation, preventing proper self-assembly.\n\nA10G and A14G: both formed assembled nanofibers and produced hydrogels with higher viscoelasticities. Both showed substantial cell adhesion, performing as effective extracellular matrix mimics.\n\nOther variants: significantly reduced cell adhesion despite containing the same RGD sequence.\n\nThe key insight is that the higher-order supramolecular structure strongly influences RGD functionality. Simply having the RGD sequence is not enough; it must be positioned where it does not disrupt self-assembly and where it is properly displayed on the nanofiber surface for integrins to access.","whyItMatters":"Self-assembling peptide hydrogels are used as tissue engineering scaffolds, wound dressings, and cell culture substrates. The RGD sequence enables cell attachment, critical for tissue regeneration. This study shows placement matters as much as presence, a crucial design rule for biomaterial engineers.","specificNumbers":"6 RGD positions tested; A6G disrupted assembly; A10G/A14G best fibers and cell adhesion; identical composition different outcomes","methodology":"Peptide chemistry and biomaterials study. RADA16 variants synthesized with glycine substitutions at different alanine positions. Self-assembly characterized by circular dichroism (secondary structure), TEM (nanofiber imaging), and rheology (gel mechanics). Cell adhesion tested on assembled scaffolds.","limitations":"Only one base peptide (RADA16) and one cell type tested. The glycine substitution changes both RGD position and overall peptide amphiphilicity simultaneously, making it hard to separate effects. In vivo tissue engineering performance was not assessed. Cell adhesion does not guarantee full tissue regeneration functionality."},{"rthcId":"RPEP-04876","title":"Analysis of the Diversity of the AvBD Gene Region in Japanese Quail.","authors":"Ishige, Taichiro; Hara, Hiromi; Hirano, Takashi; Kono, Tomohiro; Hanzawa, Kei","year":2020,"journal":"The Journal of heredity, 111(5), 436-443","doi":"10.1093/jhered/esaa035","pmid":"32852036","tags":["antimicrobial-peptides","immune-function"],"studyType":"Genomics","evidenceStrength":"moderate","keyFinding":"Genomic analysis of 99 Japanese quail revealed substantial diversity in the avian beta-defensin (AvBD) gene region:\n\nNine CjAvBD1 and 8 CjAvBD12 alleles were detected, combining into 10 haplotypes (3 were strain-specific). Next-generation sequencing of 7 homozygous haplotypes revealed 12 to 16 CjAvBD genes per haplotype.\n\nAll 7 haplotypes shared 11 common loci (CjAvBD1, -2, -4, -5, -8, -9, -10, -11, -12, -13, -14) but lacked CjAvBD3 and -7 found in chickens. Up to 5 copy number variants of CjAvBD101 (the AvBD6 ortholog) were found among haplotypes.\n\nFunctionally significant mutations were detected in CjAvBD4, -13, -14, and -101: amino acid substitutions that change the net charge of the defensin protein. Since defensin antimicrobial activity depends on positive charge for membrane interaction, these mutations could directly affect pathogen killing ability.\n\nThe quail AvBD region is uniquely organized compared to chicken, turkey, and bobwhite quail, suggesting rapid evolution of innate immune genes in galliform birds.","whyItMatters":"Japanese quail are important for biomedical research and poultry production. Defensin gene diversity directly affects disease resistance. Understanding which haplotypes provide better protection could enable selective breeding for healthier, more disease-resistant quail lines without antibiotics.","specificNumbers":"99 quail; 10 haplotypes; 12-16 genes/haplotype; up to 5 CjAvBD101 copies; charge mutations in 4 genes","methodology":"Genomic study of 99 Japanese quail from 6 inbred lines. DNA extracted from blood. Alleles identified by PCR; haplotypes assembled. Next-generation sequencing of 56-70 kb AvBD regions for 7 homozygous haplotypes. Amino acid substitutions analyzed for charge effects.","limitations":"Functional antimicrobial testing of the different alleles was not performed. Charge predictions are theoretical; actual antimicrobial effects need laboratory confirmation. Only 6 inbred lines were studied; wild quail may have additional diversity. The link between specific haplotypes and disease resistance was not tested."},{"rthcId":"RPEP-04877","title":"Hydrophobic ion pairing of a GLP-1 analogue for incorporating into lipid nanocarriers designed for oral delivery.","authors":"Ismail, Ruba; Phan, Thi Nhu Quynh; Laffleur, Flavia; Csóka, Ildikó; Bernkop-Schnürch, Andreas","year":2020,"journal":"European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 152, 10-17","doi":"10.1016/j.ejpb.2020.04.025","pmid":"32371152","tags":["exenatide","glp-1","oral-peptides","bioavailability","peptide-delivery"],"studyType":"Pharmaceutical formulation + animal pharmacokinetics","evidenceStrength":"preliminary","keyFinding":"Exenatide is a peptide drug given by injection because it is destroyed in the gut and cannot cross the intestinal wall. Hydrophobic ion pairing (HIP) makes peptides lipophilic by pairing them with surfactant counterions.\n\nTwo surfactant types were tested: cationic THA (tetraheptylammonium bromide) and anionic DOC (sodium docusate). Both formed stable complexes with exenatide.\n\nExenatide-THA was more lipophilic (log D of 2.29 in simulated intestinal fluid vs 1.2 for exenatide-DOC). When loaded into lipid nanocarriers (41% Capmul MCM, 15% Captex 355, 40% Cremophor RH, 4% propylene glycol), the THA formulation showed:\n- 10-fold enhancement in intestinal apparent membrane permeability vs free exenatide\n- 28.0% ± 5.2% relative oral bioavailability in healthy rats\n\nThe DOC formulation achieved 3-fold permeability enhancement and 16.3% ± 6.6% bioavailability.\n\nNeither formulation caused significant hemolytic activity at 0.25% concentration, indicating safety for oral use.","whyItMatters":"GLP-1 drugs like exenatide, semaglutide, and liraglutide are revolutionizing diabetes and obesity treatment, but most require injection. Oral delivery would dramatically improve patient compliance. Achieving 28% oral bioavailability for a peptide drug is remarkable; oral semaglutide (Rybelsus) has only about 1% bioavailability.","specificNumbers":"28% oral bioavailability (THA); 16% (DOC); 10x permeability enhancement; non-hemolytic; log D 2.29","methodology":"Pharmaceutical formulation study. Hydrophobic ion pairs prepared with THA and DOC surfactants. Lipophilicity measured by partition coefficients. Nanocarriers characterized for hemolytic activity. Intestinal permeability tested using standard membrane models. Oral bioavailability measured in healthy rats compared to subcutaneous injection.","limitations":"Tested in healthy rats, not diabetic animals or humans. Rat oral bioavailability does not always translate to human bioavailability. The lipid nanocarrier composition may not be optimized yet. Long-term stability of the ion-paired formulation was not assessed. The 28% bioavailability is relative to subcutaneous injection; absolute absorption may be lower."},{"rthcId":"RPEP-04878","title":"The substance P and neurokinin-1 receptor system in human thyroid cancer: an immunohistochemical study.","authors":"Isorna, Inmaculada; Esteban, Francisco; Solanellas, Juan; Coveñas, Rafael; Muñoz, Miguel","year":2020,"journal":"European journal of histochemistry : EJH, 64(2)","doi":"10.4081/ejh.2020.3117","pmid":"32363847","tags":["neuropeptides","cancer"],"studyType":"Immunohistochemistry (observational)","evidenceStrength":"preliminary","keyFinding":"Both Substance P (SP) and the neurokinin-1 receptor (NK-1R) were expressed in all thyroid tissue, normal and cancerous. But the pattern differed significantly:\n\nIn healthy thyroid: SP was found in follicular cell nuclei and colloid. NK-1R was in follicular cell cytoplasm and stroma.\n\nIn thyroid cancer: SP expanded to follicular cell cytoplasm (not just nucleus), stroma, and colloid. NK-1R appeared in colloid (not present in normal tissue).\n\nUsing the Allred scoring system (a semi-quantitative measure of protein expression), both SP and NK-1R had higher total scores in cancer compared to normal thyroid. SP in nuclei, cytoplasm, and stroma was more intense/abundant in cancer. NK-1R in cytoplasm and colloid was higher in cancer.\n\nInterestingly, SP in colloid was actually lower in cancer than in normal thyroid, and NK-1R in stroma was higher in normal tissue than cancer.\n\nAll four thyroid cancer types (papillary, follicular, medullary, anaplastic) and metastases showed the elevated pattern.","whyItMatters":"Thyroid cancer incidence has tripled over 30 years. While most cases have good prognosis with surgery, anaplastic thyroid cancer is nearly universally fatal. Finding that NK-1R is overexpressed in all thyroid cancer types, including anaplastic, opens a potential therapeutic target. NK-1R antagonists (originally developed for nausea and depression) have shown anticancer effects in preclinical studies.","specificNumbers":"SP and NK-1R in all samples; higher Allred scores in cancer; all 4 cancer types + metastases affected; SP expanded to cytoplasm in cancer","methodology":"Immunohistochemistry study of human thyroid tissue samples: papillary, follicular, medullary, and anaplastic thyroid cancer, metastases, and healthy thyroid. SP and NK-1R protein expression scored using the Allred Unit Scoring System (combines intensity and proportion).","limitations":"Immunohistochemistry shows presence but not function. Higher expression does not prove SP/NK-1R drives cancer growth. No functional studies (NK-1R antagonist testing on thyroid cancer cells). Sample sizes per cancer type not specified in the abstract. Semi-quantitative scoring is subjective. The study did not measure SP/NK-1R correlation with cancer aggressiveness or patient outcomes."},{"rthcId":"RPEP-04879","title":"A polylysine-polyhistidine fusion peptide for lysosome-targeted protein delivery.","authors":"Iwasaki, Takashi; Murakami, Nodoka; Kawano, Tsuyoshi","year":2020,"journal":"Biochemical and biophysical research communications, 533(4), 905-912","doi":"10.1016/j.bbrc.2020.09.087","pmid":"33008588","tags":["cell-penetrating","peptide-delivery"],"studyType":"In vitro (proof-of-concept)","evidenceStrength":"preliminary","keyFinding":"The K10H16 fusion peptide delivers functional enzymes to intracellular lysosomes via electrostatic complexation, restoring normal cell growth in lysosomal storage disease cells.","whyItMatters":"Lysosomal storage diseases currently require enzyme replacement therapy with limited cell penetration. A peptide carrier delivering enzymes directly to lysosomes could dramatically improve treatment efficacy.","specificNumbers":"K10H16 (26 AA); lysosomal targeting confirmed; GLA delivered; LSD cell proliferation restored; simple electrostatic mixing","methodology":"Peptide synthesis, fluorescent protein delivery tracking, alpha-galactosidase A delivery to LSD cells, and cell proliferation assays.","limitations":"In vitro proof-of-concept only. No in vivo data on peptide stability, biodistribution, or therapeutic efficacy."},{"rthcId":"RPEP-04880","title":"Triggering Supramolecular Hydrogelation Using a Protein-Peptide Coassembly Approach.","authors":"Jain, Rashmi; Pal, Vijay Kumar; Roy, Sangita","year":2020,"journal":"Biomacromolecules, 21(10), 4180-4193","doi":"10.1021/acs.biomac.0c00984","pmid":"32786522","tags":["peptide-design","bioavailability"],"studyType":"Biomaterials (proof-of-concept)","evidenceStrength":"preliminary","keyFinding":"This is the first demonstration that protein-peptide coassembly can induce gelation in a non-gelator peptide. The key findings:\n\nA dipeptide that forms aggregates but not gels when alone was transformed into a fiber-forming hydrogel when proteins were added. The protein-peptide interactions converted aggregate-like structures into ordered fibrillar nanostructures.\n\nThe interactions were purely non-covalent (electrostatic, hydrophobic, hydrogen bonding). Biolayer interferometry and molecular docking confirmed dissociation constants and binding energies consistent with non-specific protein-peptide interactions.\n\nTunability: different proteins had different binding affinities to the peptide, producing gels with different mechanical and structural properties at the same peptide concentration. Simply changing the protein type or concentration tuned the gel.\n\nEnzyme entrapment: an enzyme protein was successfully trapped within the gel network during coassembly without losing catalytic activity. This creates a scaffold that can both provide structural support and perform chemical reactions.","whyItMatters":"Self-assembling peptide hydrogels are important biomaterials but have limited tunability. This protein-peptide coassembly approach provides a simple way to control gel properties by varying the protein component. Retaining enzyme activity inside the gel opens applications in biosensing, drug delivery, and tissue engineering.","specificNumbers":"First protein-peptide coassembly gelation; non-covalent; tunable mechanics; enzyme activity preserved; aggregate→fiber transformation","methodology":"Biomaterials and biophysics study. Dipeptide-protein coassembly characterized by rheology (gel mechanics), TEM/SEM (nanostructure), circular dichroism (secondary structure), biolayer interferometry (binding kinetics), and molecular docking. Enzyme activity assays confirmed functional retention.","limitations":"Proof of concept with limited protein-peptide combinations tested. Long-term stability of the coassembled gels was not assessed. The non-specific nature of the interactions may limit precision. Biological applications (cell culture, implantation) were not tested. Scalability of the approach is unknown."},{"rthcId":"RPEP-04881","title":"The Role of Oxytocin in Cardiovascular Protection.","authors":"Jankowski, Marek; Broderick, Tom L; Gutkowska, Jolanta","year":2020,"journal":"Frontiers in psychology, 11, 2139","doi":"10.3389/fpsyg.2020.02139","pmid":"32982875","tags":["oxytocin","cardiovascular","neuroprotection"],"studyType":"Review","evidenceStrength":"moderate","keyFinding":"The review synthesizes evidence for multiple cardioprotective mechanisms of oxytocin:\n\nDirect cardiac protection: oxytocin reduces infarct size and improves functional recovery in ischemia-reperfusion models. When given at the onset of reperfusion, it enhances cardiomyocyte viability by activating PI3K and Akt phosphorylation.\n\nNitric oxide pathway: oxytocin stimulates local release of atrial natriuretic peptide (ANP) in the heart, which generates cGMP and nitric oxide synthesis. This vasodilatory and cytoprotective cascade is a key mechanism.\n\nAnti-inflammatory: oxytocin reduces expression of pro-inflammatory cytokines and decreases immune cell infiltration into damaged heart tissue.\n\nRegeneration: oxytocin stimulates differentiation of stem cells into cardiomyocyte lineages and promotes generation of endothelial and smooth muscle cells, supporting angiogenesis (new blood vessel growth).\n\nMetabolic protection: oxytocin increases glucose uptake by cardiomyocytes, reduces hypertrophy, decreases oxidative stress, and protects mitochondria.\n\nSignaling pathways: RISK (reperfusion injury salvage kinase) and STAT (signal transducer and activator of transcription) cardioprotective pathways are both involved.","whyItMatters":"Heart attack is the leading cause of death worldwide. Limiting reperfusion injury (damage that occurs when blood flow is restored) could save millions of lives. Oxytocin's multi-pronged cardiac protection, from immediate cell survival to long-term regeneration, makes it a compelling therapeutic candidate.","specificNumbers":"Reduced infarct size; PI3K/Akt activated; ANP-cGMP-NO pathway; anti-inflammatory; stem cell differentiation; RISK/STAT pathways","methodology":"Narrative review of preclinical studies (cell culture, isolated heart, and animal models) examining oxytocin's cardiac effects, cellular mechanisms, and signaling pathways.","limitations":"Nearly all evidence is from animal models and cell cultures. Human clinical data for cardiac oxytocin use is essentially absent. Oxytocin's cardiovascular effects may differ between species. Dosing, timing, and route of administration for cardiac protection in humans are unknown. Oxytocin also has effects on blood pressure and fluid balance that could complicate cardiac use."},{"rthcId":"RPEP-04882","title":"Risk of Major Adverse Cardiovascular Events, Severe Hypoglycemia, and All-Cause Mortality for Widely Used Antihyperglycemic Dual and Triple Therapies for Type 2 Diabetes Management: A Cohort Study of All Danish Users.","authors":"Jensen, Morten Hasselstrøm; Kjolby, Mads; Hejlesen, Ole; Jakobsen, Poul Erik; Vestergaard, Peter","year":2020,"journal":"Diabetes care, 43(6), 1209-1218","doi":"10.2337/dc19-2535","pmid":"32238426","tags":["glp-1","cardiovascular","diabetes"],"studyType":"Population-based cohort study","evidenceStrength":"strong","keyFinding":"This massive real-world study compared outcomes across multiple diabetes drug combinations:\n\nWorst performer: metformin plus sulfonylurea (SU) had the highest risk of cardiovascular events and death. Metformin plus basal insulin had the highest severe hypoglycemia risk.\n\nBest cardiovascular protection: regimens including a GLP-1 receptor agonist had the lowest MACE risk.\n\nBest overall: metformin + SGLT2 inhibitor + GLP-1 had the lowest risk for all three endpoints (cardiovascular events, severe hypoglycemia, and all-cause mortality).\n\nKey clinical insight: adding GLP-1 to metformin + basal insulin reduced all three endpoints compared to metformin + insulin alone, especially severe hypoglycemia. This suggests GLP-1 agonists should be considered before or alongside insulin.\n\nThe results do not support sulfonylurea as the second-line treatment choice, a finding that aligns with evolving guidelines moving away from SU.","whyItMatters":"Real-world data from an entire national population is powerful because it captures outcomes that clinical trials may miss: medication adherence, complex patients, and long-term effects. This study provides the strongest real-world evidence that GLP-1 agonists should be prioritized over sulfonylureas as second-line diabetes drugs, and that the triple combination with SGLT2 inhibitors is optimal.","specificNumbers":"66,807 patients; 20 years; MET+SU worst; MET+SGLT2i+GLP-1 best; GLP-1 addition to MET+insulin reduced all endpoints","methodology":"Population-based cohort study using 20 years of data from the Danish National Patient Registry. All 66,807 type 2 diabetes patients treated with metformin plus various second- and third-line therapies were analyzed. Cox regression models assessed risk of MACE, severe hypoglycemia, and all-cause mortality across drug combinations.","limitations":"Observational study subject to confounding by indication. Sicker patients may receive insulin (making insulin look worse) while healthier patients may start GLP-1 drugs (making them look better). No randomization. Drug-specific effects within GLP-1 and SGLT2 classes were not separated. Some combinations had small patient numbers, reducing power for those comparisons."},{"rthcId":"RPEP-04883","title":"Substance P enhances the local activation of NK1R-expressing c-kit+ cardiac progenitor cells in right atrium of ischemia/reperfusion-injured heart.","authors":"Jeong, Yun-Mi; Cheng, Xian Wu; Lee, Kyung Hye; Lee, Sora; Cho, Haneul; Kim, Weon","year":2020,"journal":"BMC molecular and cell biology, 21(1), 41","doi":"10.1186/s12860-020-00286-x","pmid":"32517655","tags":["neuropeptides","cardiovascular","wound-healing"],"studyType":"Animal study (rats)","evidenceStrength":"moderate","keyFinding":"After ischemia/reperfusion injury in rats, Substance P (5 nmol/kg injection) had specific effects on the right atrium (RA):\n\nSP promoted expression of c-Kit, GATA4, Oct4, Nanog, and Sox2 only in the RA, not in other heart chambers. These are markers of cardiac progenitor cells (CPCs) and stem cell pluripotency.\n\nIn ex vivo RA explant outgrowths, NK1R-expressing c-Kit+/Nkx2.5+/GATA4+ CPCs migrated approximately 2-fold more from SP-treated RA tissue compared to untreated I/R tissue.\n\nSP treatment promoted CPC proliferation, migration, cardiosphere formation (3D cell clusters indicating stemness), and differentiation into cardiomyocytes.\n\nAll effects were blocked by the NK1R antagonist RP67580, confirming the SP/NK1R pathway is required. The SP/NK1R system acts as a key mediator of CPC expansion in the RA within 24 hours after ischemia/reperfusion.\n\nThis identifies the right atrium as a specific niche for SP-responsive cardiac stem cells.","whyItMatters":"Heart attacks kill heart muscle cells that cannot regenerate. Activating the heart's own progenitor cells could enable natural repair. This study shows Substance P specifically activates cardiac progenitor cells in the right atrium after injury. If this SP/NK1R pathway can be harnessed, it could enhance natural heart repair after heart attack.","specificNumbers":"88 rats; SP 5nmol/kg; 2-fold CPC migration increase; Oct4/Nanog/Sox2/c-Kit/GATA4 up in RA only; NK1R antagonist blocked all effects","methodology":"Animal study with 88 Sprague-Dawley rats in 4 groups (n=22 each): sham, I/R only, SP+I/R, and NK1R antagonist+SP+I/R. Left anterior descending artery occluded 40 minutes followed by 1 day reperfusion. SP or SP+RP67580 injected. Both atria, ventricles, and heart apex collected at 1 day. Gene expression, immunohistochemistry, and ex vivo explant outgrowth assays performed.","limitations":"Tested in rats, not humans. The 24-hour time point captures only the initial response; long-term cardiac repair was not assessed. Whether activated CPCs actually integrate into damaged myocardium and improve heart function was not tested. SP has many other effects (pain, inflammation, vasodilation) that could complicate therapeutic use. The right atrium specificity may not translate to humans."},{"rthcId":"RPEP-04884","title":"Multi-functional nanocomplex codelivery of Trp2 and R837 to activate melanoma-specific immunity.","authors":"Ji, Zhonghua; Tan, Zeng; Li, Min; Tao, Jin; Guan, Enshuang; Du, Junrong; Hu, Ying","year":2020,"journal":"International journal of pharmaceutics, 582, 119310","doi":"10.1016/j.ijpharm.2020.119310","pmid":"32276088","tags":["peptide-delivery","cancer"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"The team created a multi-part nanocomplex that co-delivers a melanoma antigen peptide (Trp2) and a toll-like receptor 7 agonist (R837) to dendritic cells. Both ingredients dissolve poorly in water, which has made combined delivery difficult until now.\n\nThey used a sugar-coated cyclodextrin shell to carry R837 and target mannose receptors on dendritic cells. A fusion peptide combined Trp2 with a cell-penetrating sequence (TAT) to help it get inside cells. Sodium alginate wrapped everything together and added its own immune-boosting effect.\n\nThe nanocomplex improved cellular uptake and significantly increased the release of Th1 cytokines, which are signals linked to anti-tumor immunity.","whyItMatters":"Getting a cancer antigen and an immune booster into the same immune cell at the same time is a major challenge in cancer vaccine development. This nanocomplex solves a real delivery problem by targeting dendritic cells directly and carrying both ingredients in one package.\n\nIf this approach works in animal models and eventually humans, it could lead to more effective melanoma vaccines that train the immune system to recognize and destroy cancer cells.","specificNumbers":"Delivered 2 hydrophobic agents via single nanocomplex; increased Th1 cytokine secretion","methodology":"This was a cell-based laboratory study. Researchers assembled the nanocomplex using mannosylated beta-cyclodextrin loaded with R837, a TAT-Trp2 fusion peptide, and sodium alginate. They tested cellular uptake and cytokine secretion in dendritic cell cultures.","limitations":"This study was done entirely in cell cultures. No animal or human testing was reported, so it is unknown whether the nanocomplex would trigger meaningful anti-tumor immunity in a living organism.\n\nThe long-term stability of the nanocomplex and its behavior in blood circulation were not tested."},{"rthcId":"RPEP-04885","title":"D-Amino Acids in Peptides from Animals, Including Human: Occurrence, Structure, Bioactivity and Pharmacology.","authors":"Jimenez, Elsie C","year":2020,"journal":"Current protein & peptide science, 21(6), 622-637","doi":"10.2174/1389203721666200426233758","pmid":"32338216","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04886","title":"Protective Effect of Glycomacropeptide on the Atopic Dermatitis-Like Dysfunctional Skin Barrier in Rats.","authors":"Jiménez, Mariela; Muñoz, Fabiola C; Cervantes-García, Daniel; Cervantes, Maritza M; Hernández-Mercado, Alicia; Barrón-García, Berenice; Moreno Hernández-Duque, José L; Rodríguez-Carlos, Adrián; Rivas-Santiago, Bruno; Salinas, Eva","year":2020,"journal":"Journal of medicinal food, 23(11), 1216-1224","doi":"10.1089/jmf.2019.0247","pmid":"32155356","tags":["antimicrobial-peptides","collagen-peptides","gut-health"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Glycomacropeptide (GMP) given by mouth significantly increased filaggrin, beta-defensin 2, and cathelicidin expression in damaged skin. These are proteins critical for maintaining the skin barrier and fighting off infections.\n\nGMP also strongly reduced epidermal thickening and IFN-gamma expression in damaged skin. This means it calmed the inflammatory response driving the eczema-like condition.\n\nOn the microbiome side, GMP prevented Staphylococcus aureus colonization of the skin, which is a major trigger for eczema flares. In the gut, GMP boosted Bifidobacterium levels and increased short-chain fatty acids (acetic acid and butyric acid), especially when given before eczema was induced.","whyItMatters":"Eczema affects millions of people, and maintaining the skin barrier is one of the most important parts of treatment. This study shows a food-derived peptide could help restore that barrier from the inside out, working through the gut-skin connection.\n\nThe fact that GMP worked both preventively and as treatment, and that it blocked S. aureus colonization, makes it especially interesting for people who deal with recurring eczema flares.","specificNumbers":"Increased filaggrin, beta-defensin 2, cathelicidin; reduced epidermal thickening and IFN-gamma; prevented S. aureus colonization; boosted Bifidobacterium and fecal SCFAs","methodology":"Researchers induced eczema-like dermatitis on rat skin using repeated applications of DNCB (a chemical irritant). Rats received oral GMP either before or after eczema induction. They measured skin proteins by immunoblot and immunohistochemistry, skin thickness by histochemistry, IFN-gamma and microbiota by PCR, and fecal short-chain fatty acids by gas chromatography.","limitations":"This was an animal study using chemically induced eczema, which does not perfectly mimic human atopic dermatitis. The doses used in rats may not translate directly to human dosing.\n\nThe study did not measure how long the benefits lasted after stopping GMP treatment."},{"rthcId":"RPEP-04887","title":"Identification of novel DPP-IV inhibitory peptides from Atlantic salmon (Salmo salar) skin.","authors":"Jin, Ritian; Teng, Xiangyu; Shang, Jiaqi; Wang, Dangfeng; Liu, Ning","year":2020,"journal":"Food research international (Ottawa, Ont.), 133, 109161","doi":"10.1016/j.foodres.2020.109161","pmid":"32466942","tags":["collagen-peptides","diabetes","bioactive-peptides"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Salmon skin collagen was broken down by four different enzymes. The trypsin-digested version showed the strongest DPP-IV inhibition at 66% at 10 mg/mL.\n\nAfter separating the fragments by size, the smallest fraction (under a certain molecular weight) had an IC50 of 0.79 mg/mL. Further purification identified a novel peptide, LDKVFR, with an IC50 of 0.1 mg/mL (128.71 micromolar).\n\nMolecular docking showed LDKVFR binds to DPP-IV through six hydrogen bonds and eight hydrophobic interactions, explaining its inhibitory activity.","whyItMatters":"DPP-IV inhibitors are an established class of diabetes medications. Finding natural peptides from food sources like salmon skin that can block this enzyme opens the door to food-derived alternatives or supplements.\n\nSalmon skin is a fish processing byproduct, so using it to produce bioactive peptides could add value to waste material while creating potential health products.","specificNumbers":"66.12% DPP-IV inhibition at 10 mg/mL (trypsin hydrolysate); LDKVFR IC50 = 0.1 mg/mL (128.71 μM); 6 hydrogen bonds, 8 hydrophobic interactions","methodology":"This was a laboratory study. Researchers hydrolyzed salmon skin collagen with pepsin, trypsin, papain, or Alcalase. Fractions were separated by ultrafiltration and chromatography. DPP-IV inhibition was measured using an enzymatic assay. Binding was modeled using molecular docking software.","limitations":"This was entirely a lab-based study. No cell, animal, or human testing was done to see if LDKVFR survives digestion or reaches the bloodstream in active form.\n\nThe IC50 of 128 micromolar is relatively high compared to pharmaceutical DPP-IV inhibitors, which work at nanomolar concentrations."},{"rthcId":"RPEP-04888","title":"Prevalent and Diverse Intratumoral Oncoprotein-Specific CD8+ T Cells within Polyomavirus-Driven Merkel Cell Carcinomas.","authors":"Jing, Lichen; Ott, Mariliis; Church, Candice D; Kulikauskas, Rima M; Ibrani, Dafina; Iyer, Jayasri G; Afanasiev, Olga K; Colunga, Aric; Cook, Maclean M; Xie, Hong; Greninger, Alexander L; Paulson, Kelly G; Chapuis, Aude G; Bhatia, Shailender; Nghiem, Paul; Koelle, David M","year":2020,"journal":"Cancer immunology research, 8(5), 648-659","doi":"10.1158/2326-6066.CIR-19-0647","pmid":"32179557","tags":["cancer","peptide-vaccines"],"studyType":"human tissue study","evidenceStrength":"moderate","keyFinding":"Tumor-infiltrating lymphocytes from 9 of 12 patients (75%) contained CD8+ T cells that recognized Merkel cell polyomavirus T-antigen. Each patient's immune cells recognized between 1 and 8 different viral epitopes.\n\nAnalysis of 16 identified epitopes showed that 97% of patients with virus-positive Merkel cell carcinoma had the HLA alleles needed to mount CD8+ T cell responses against the viral proteins.\n\nThe amino acid region 70-110 of the large T antigen was especially rich in immune targets, while the oncogenic domains were not commonly recognized. This is important because a vaccine could focus on the immunogenic region while avoiding the cancer-causing parts.","whyItMatters":"About half of Merkel cell carcinoma patients respond to immune checkpoint inhibitors. Finding that most tumors already contain virus-specific immune cells suggests the raw ingredients for an immune response are present. A vaccine could boost these existing immune cells.\n\nThe fact that immunogenic regions are separate from oncogenic regions means a vaccine could be designed that is both effective and safe, without risk of promoting cancer growth.","specificNumbers":"9/12 (75%) had virus-specific TILs; 1-8 epitopes per patient; 16 epitopes mapped; 97% HLA coverage","methodology":"Researchers extracted tumor-infiltrating lymphocytes from 12 Merkel cell carcinoma patients. They used artificial antigen-presenting cells, synthetic peptides, HLA-peptide tetramers, and dendritic cells to identify which viral epitopes the immune cells recognized. They also analyzed HLA allele coverage across patients.","limitations":"This was a small study with only 12 patients. While the HLA coverage analysis extended to a broader population, the direct T cell findings came from a limited sample.\n\nThe study did not test whether boosting these T cell responses with a vaccine would actually shrink tumors."},{"rthcId":"RPEP-04889","title":"A gold mine for drug discovery: Strategies to develop cyclic peptides into therapies.","authors":"Jing, Xiaoshu; Jin, Kang","year":2020,"journal":"Medicinal research reviews, 40(2), 753-810","doi":"10.1002/med.21639","pmid":"31599007","tags":["cyclic-peptides","peptide-drug-development"],"studyType":"review","evidenceStrength":"n/a (review)","keyFinding":"Cyclic peptides offer a middle ground between small molecule drugs and large biologics. Their ring structure gives them better cell permeability and metabolic stability compared to linear peptides, while still allowing them to bind large protein surfaces that small molecules cannot reach.\n\nMore than 40 cyclic peptide drugs have reached clinical approval, most derived from natural products. Newer approaches including rational design, mRNA display, phage display, and DNA-encoded libraries are creating cyclic peptides against targets that nature never addressed.\n\nThe review covers multiple macrocyclization strategies including disulfide bonds, lactam bridges, hydrocarbon stapling, and click chemistry, each with different trade-offs in terms of stability, permeability, and ease of synthesis.","whyItMatters":"Many important disease targets involve protein-protein interactions that small molecule drugs cannot disrupt. Cyclic peptides can reach these targets while being more stable and cell-permeable than linear peptides.\n\nThis review provides a roadmap of current strategies, helping researchers choose the right approach for their specific target.","specificNumbers":"40+ clinically approved cyclic peptide drugs; multiple macrocyclization strategies surveyed","methodology":"This is a comprehensive literature review covering cyclic peptide drug development, including approved drugs, clinical candidates, and discovery platforms. It surveys macrocyclization chemistry, structure-activity relationships, and in vitro evolution methods.","limitations":"As a review article, this does not present new experimental data. The strategies described vary widely in their stage of development, from approved drugs to early-stage concepts.\n\nThe review may not capture the most recent advances published after its completion."},{"rthcId":"RPEP-04890","title":"A Relative Cost of Control Analysis of Once-Weekly Semaglutide Versus Exenatide Extended-Release, Dulaglutide and Liraglutide in the UK.","authors":"Johansen, Pierre; Sandberg, Anna; Capehorn, Matthew","year":2020,"journal":"Advances in therapy, 37(3), 1248-1259","doi":"10.1007/s12325-020-01242-z","pmid":"32048148","tags":["semaglutide","glp-1-receptor-agonists","diabetes","weight-loss"],"studyType":"cost-effectiveness analysis","evidenceStrength":"moderate","keyFinding":"Annual per-patient costs were similar across all four GLP-1 receptor agonists in the UK market. However, once-weekly semaglutide consistently outperformed the others in getting patients to treatment goals.\n\nFor the composite endpoint of HbA1c below 7.0% without weight gain or low blood sugar episodes, the competing drugs fell short: exenatide ER was 50.0% less effective, liraglutide was 51.3% less effective, and dulaglutide was 21.6% less effective than semaglutide.\n\nSemaglutide also led in single endpoints including HbA1c targets (below 7.0% and below 7.5%) and meaningful weight loss (5% or more body weight reduction).","whyItMatters":"When multiple drugs in the same class cost about the same, the one that helps the most patients reach their goals offers the best value. This analysis showed semaglutide delivered more clinical benefit per pound spent across every measured outcome.\n\nFor healthcare systems making formulary decisions, this type of analysis helps justify choosing one drug over another when prices are similar.","specificNumbers":"Exenatide ER 50.0% less effective; liraglutide 51.3% less effective; dulaglutide 21.6% less effective vs semaglutide at composite endpoint","methodology":"This was a cost-of-control analysis using clinical data from the SUSTAIN trial program. Researchers compared the proportion of patients reaching various treatment targets across the four drugs and divided annual UK drug costs by efficacy rates to calculate cost per responder.","limitations":"This analysis used data from the SUSTAIN clinical trials, which may not perfectly reflect real-world outcomes. Different patient populations, adherence rates, and healthcare settings could change the results.\n\nPrices were based on July 2019 UK wholesale costs, which may have changed since then."},{"rthcId":"RPEP-04891","title":"GLP-1 Analog Modulates Appetite, Taste Preference, Gut Hormones, and Regional Body Fat Stores in Adults with Obesity.","authors":"Kadouh, Hoda; Chedid, Victor; Halawi, Houssam; Burton, Duane D; Clark, Matthew M; Khemani, Disha; Vella, Adrian; Acosta, Andres; Camilleri, Michael","year":2020,"journal":"The Journal of clinical endocrinology and metabolism, 105(5), 1552-63","doi":"10.1210/clinem/dgz140","pmid":"31665455","tags":["glp-1-receptor-agonists","weight-loss","obesity"],"studyType":"randomized controlled trial","evidenceStrength":"moderate","keyFinding":"Compared to placebo, liraglutide 3 mg daily significantly reduced how much food participants wanted to eat, their desire for sweet, salty, savory, and fatty foods, and the maximum volume of a nutrient drink they could tolerate. Participants also reported feeling fuller after meals.\n\nLiraglutide increased postprandial PYY levels (a satiety hormone) while decreasing active GLP-1 levels relative to baseline. This suggests the drug changes the gut hormone environment beyond just mimicking GLP-1.\n\nBody composition scans showed significant reductions in total body fat, trunk fat, and both upper and lower body fat. Lean body mass was preserved, meaning the weight lost was predominantly fat.","whyItMatters":"One of the biggest concerns with weight loss drugs is losing muscle along with fat. This study showed liraglutide preferentially reduced fat while preserving lean mass, which is important for long-term metabolic health.\n\nThe changes in taste preference are also notable. Reducing the desire for sweet and fatty foods could help people maintain weight loss after treatment ends.","specificNumbers":"35 completers; 17 liraglutide, 18 placebo; 16 weeks; reduced total/trunk/limb fat; preserved lean mass; increased PYY, decreased active GLP-1","methodology":"This was a substudy of a double-blind, placebo-controlled, randomized 16-week trial. Forty obese adults received weight management counseling, monthly behavioral therapy, and either liraglutide (escalated to 3 mg daily) or placebo. Appetite and taste preferences were rated every 30 minutes for 5 hours after a nutrient drink. Body composition was measured by DEXA scan.","limitations":"This was a small study with only 35 completers. The 16-week duration cannot show whether the taste preference changes persist long-term or after stopping the drug.\n\nAll participants received behavioral therapy, so the liraglutide effects cannot be fully separated from the counseling effects."},{"rthcId":"RPEP-04892","title":"Peptidomimetics prepared by tail-to-side chain one component peptide stapling inhibit Alzheimer's amyloid-β fibrillogenesis.","authors":"Kalita, Sujan; Kalita, Sourav; Paul, Ashim; Sarkar, Amar; Mandal, Bhubaneswar","year":2020,"journal":"Chemical science, 11(16), 4171-4179","doi":"10.1039/c9sc06076f","pmid":"34122880","tags":["cyclic-peptides","neurological-conditions","peptide-drug-development"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"The team used a \"tail-to-side chain\" stapling method to create a library of modified peptides. These stapled peptides modulated the self-association and fibril formation of amyloid-beta 1-40, the protein fragment central to Alzheimer's pathology.\n\nThe stapled peptides also disrupted preformed fibrillar aggregates, converting them into non-toxic species. This dual action, preventing new aggregation and breaking up existing fibrils, is particularly valuable.\n\nThe ring shape made the peptides significantly more resistant to proteolytic enzymes, which would normally break down linear peptides quickly. This improved stability is essential for any potential therapeutic use.","whyItMatters":"Alzheimer's disease has no effective treatment targeting amyloid aggregation. Finding peptides that can both prevent new clumps and break up existing ones addresses two aspects of the disease at once.\n\nThe improved enzyme resistance from stapling solves a major problem with peptide drugs, which usually get broken down too quickly to be useful.","specificNumbers":"Library of stapled peptides; modulated Aβ1-40 aggregation; disrupted preformed fibrils; increased proteolytic stability","methodology":"This was a laboratory study. Researchers synthesized stapled peptides through lactamization (forming a ring via a chemical bond). They tested the peptides against amyloid-beta 1-40 aggregation using standard fibrillogenesis assays and evaluated proteolytic stability in the presence of enzymes.","limitations":"This was entirely a lab study with no cell viability, animal, or human testing. Whether these peptides can cross the blood-brain barrier and work in a living brain is unknown.\n\nThe non-toxic nature of the disrupted aggregates was stated but the extent of toxicity testing was limited."},{"rthcId":"RPEP-04893","title":"Bulevirtide: First Approval.","authors":"Kang, Connie; Syed, Yahiya Y","year":2020,"journal":"Drugs, 80(15), 1601-1605","doi":"10.1007/s40265-020-01400-1","pmid":"32926353","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04894","title":"A brain tumor-homing tetra-peptide delivers a nano-therapeutic for more effective treatment of a mouse model of glioblastoma.","authors":"Kang, Rae Hyung; Jang, Jeong-Eun; Huh, Eugene; Kang, Seong Jae; Ahn, Dae-Ro; Kang, Jae Seung; Sailor, Michael J; Yeo, Seung Geun; Oh, Myung Sook; Kim, Dokyoung; Kim, Hyo Young","year":2020,"journal":"Nanoscale horizons, 5(8), 1213-1225","doi":"10.1039/d0nh00077a","pmid":"32510090","tags":["peptide-delivery","cancer","cell-penetrating-peptides"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"The SIWV peptide was identified from an isoform of annexin-A3, a human membrane-interacting protein. It showed remarkable specificity for glioblastoma tissue both in cell cultures and in living mice.\n\nThe peptide enters cells through a caveolin-mediated endocytosis pathway, confirmed through receptor inhibition and genetic knockdown experiments.\n\nWhen grafted onto porous silicon nanoparticles loaded with the cancer drug SN-38, SIWV-targeted nanoparticles showed significantly better tumor targeting than scrambled-peptide controls in a mouse brain tumor model. The treatment also showed statistically significant anti-tumor efficacy (P < 0.05) compared to free SN-38.","whyItMatters":"Glioblastoma is the most aggressive brain tumor, and getting drugs past the blood-brain barrier to reach these tumors is one of the biggest challenges in oncology. A peptide that specifically homes to glioblastoma tissue could dramatically improve drug delivery.\n\nThe fact that SIWV is only four amino acids long makes it relatively simple to manufacture and attach to various drug carriers.","specificNumbers":"4-amino-acid peptide (SIWV); P < 0.05 vs free SN-38; enhanced targeting vs scrambled control","methodology":"This was a preclinical study using both cell cultures and a mouse xenograft model of glioblastoma. Researchers identified the SIWV sequence from annexin-A3, characterized its cell entry mechanism through inhibition studies, and tested therapeutic efficacy by loading porous silicon nanoparticles with SN-38 and grafting them with SIWV via a PEG linker.","limitations":"This was tested in a mouse xenograft model, which uses human tumor cells implanted into immune-compromised mice. This does not fully replicate the human brain tumor environment or immune system.\n\nThe study did not test whether SIWV crosses the blood-brain barrier when tumors are intact, which is critical for clinical translation."},{"rthcId":"RPEP-04895","title":"Macrocyclization of an all-d linear α-helical peptide imparts cellular permeability.","authors":"Kannan, Srinivasaraghavan; Aronica, Pietro G A; Ng, Simon; Gek Lian, Dawn Thean; Frosi, Yuri; Chee, Sharon; Shimin, Jiang; Yuen, Tsz Ying; Sadruddin, Ahmad; Kaan, Hung Yi Kristal; Chandramohan, Arun; Wong, Jin Huei; Tan, Yaw Sing; Chang, Zi Wei; Ferrer-Gago, Fernando J; Arumugam, Prakash; Han, Yi; Chen, Shiying; Rénia, Laurent; Brown, Christopher J; Johannes, Charles W; Henry, Brian; Lane, David P; Sawyer, Tomi K; Verma, Chandra S; Partridge, Anthony W","year":2020,"journal":"Chemical science, 11(21), 5577-5591","doi":"10.1039/c9sc06383h","pmid":"32874502","tags":["cyclic-peptides","cancer","peptide-drug-development"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"The team started with a known all-D linear peptide that potently inhibits the p53-Mdm2 interaction in a test tube but cannot enter cells. Using computational modeling, they designed optimal staple placement to create macrocyclic versions.\n\nThe resulting stapled and stitched all-D peptides showed increased alpha-helical structure, improved binding to the Mdm2 target, complete resistance to proteolytic enzymes, and, most importantly, cellular activity.\n\nThis represents the first demonstration that combining D-amino acids with hydrocarbon stapling can produce peptides that are both enzyme-proof and cell-permeable, overcoming two of the biggest barriers to peptide drug development.","whyItMatters":"Peptide drugs face two main problems: enzymes break them down, and they cannot get into cells. D-amino acids solve the first problem but not the second. Stapling solves the second but not always the first. Combining both strategies simultaneously could open the door to a new class of highly stable, cell-permeable peptide therapeutics.\n\nThe p53-Mdm2 interaction is one of the most important targets in cancer research, and blocking it could reactivate the body's natural tumor suppressor.","specificNumbers":"First all-D stapled peptides with cellular activity; complete proteolytic stability; improved helicity and binding","methodology":"This was a laboratory study combining computational modeling and peptide chemistry. Researchers used molecular modeling to predict optimal staple positions on an all-D peptide scaffold. They synthesized stapled and stitched variants and tested them for helicity (circular dichroism), target binding, proteolytic stability, and cellular activity against the p53-Mdm2 interaction.","limitations":"This is an early proof-of-concept study. The cellular activity was demonstrated but detailed potency data, selectivity profiling, and in vivo testing were not reported.\n\nWhether this combined strategy works for targets beyond p53-Mdm2 remains to be seen."},{"rthcId":"RPEP-04896","title":"Incretin combination therapy for the treatment of non-alcoholic steatohepatitis.","authors":"Kannt, Aimo; Madsen, Andreas Nygaard; Kammermeier, Claire; Elvert, Ralf; Klöckener, Tim; Bossart, Martin; Haack, Torsten; Evers, Andreas; Lorenz, Katrin; Hennerici, Wolfgang; Rocher, Corinne; Böcskei, Zsolt; Guillemot, Jean-Claude; Mikol, Vincent; Pattou, Francois; Staels, Bart; Wagner, Michael","year":2020,"journal":"Diabetes, obesity & metabolism, 22(8), 1328-1338","doi":"10.1111/dom.14035","pmid":"32196896","tags":["glp-1-receptor-agonists","obesity","diabetes"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"Mice were fed a high-fat, high-fructose, high-cholesterol diet for 36 weeks to develop NASH with fibrosis, then treated for 8 weeks. Low-dose glucagon or GIP alone did not affect body weight, liver fat, or liver damage scores. But when combined with GLP-1 receptor activation, both glucagon and GIP provided additional benefits.\n\nThe triple combination (GLP-1 + glucagon + GIP) and a dual GLP-1/glucagon peptide both significantly reduced the NAFLD activity score more than high-dose liraglutide. This happened at comparable levels of weight loss, meaning the extra liver improvement came from the hormones themselves, not just from losing weight.\n\nThis supports the idea that multi-receptor agonists targeting two or three gut hormone receptors could be more effective for NASH than GLP-1 drugs alone.","whyItMatters":"NASH is a leading cause of liver disease with limited treatment options. Current GLP-1 drugs help partly through weight loss, but this study shows that adding glucagon and GIP receptor activation provides liver benefits beyond what weight loss alone can explain.\n\nThis research supports the development of multi-agonist drugs like tirzepatide and experimental triple agonists for liver disease.","specificNumbers":"36 weeks diet + 8 weeks treatment; triple combo and dual peptide beat liraglutide on NAFLD activity score at comparable weight loss","methodology":"Mice were pre-fed a NASH-inducing diet for 36 weeks, then treated for 8 weeks with subcutaneous injections of individual receptor agonists (GLP-1, glucagon, GIP), dual or triple combinations, a dual GLP-1/glucagon peptide, or liraglutide. Researchers measured body weight, liver triglycerides, and histological disease scores.","limitations":"This was a mouse study using a diet-induced NASH model, which does not perfectly replicate human NASH. The 8-week treatment period may not capture longer-term effects or safety concerns.\n\nThe individual agonist doses were low, which may explain why they had no effect alone. Higher doses might have shown different results."},{"rthcId":"RPEP-04897","title":"Effect of growth hormone treatment on circulating levels of NT-proBNP in patients with ischemic heart failure.","authors":"Karason, Kristjan; Bobbio, Emanuele; Polte, Christian; Bollano, Entela; Peterson, Magnus; Cittadini, Antonio; Caidahl, Kenneth; Hjalmarson, Åke; Bengtsson, Bengt-Åke; Ekelund, Jan; Swedberg, Karl; Isgaard, Jörgen","year":2020,"journal":"Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society, 55, 101359","doi":"10.1016/j.ghir.2020.101359","pmid":"33099227","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04898","title":"Therapeutic hypothermia after cardiac arrest increases the plasma level of B-type natriuretic peptide.","authors":"Kashiwagi, Yusuke; Komukai, Kimiaki; Kimura, Haruka; Okuyama, Toraaki; Maehara, Tomoki; Fukushima, Keisuke; Kamba, Takahito; Oki, Yoshitsugu; Shirasaki, Keisuke; Kubota, Takeyuki; Miyanaga, Satoru; Nagoshi, Tomohisa; Yoshimura, Michihiro","year":2020,"journal":"Scientific reports, 10(1), 15545","doi":"10.1038/s41598-020-72703-2","pmid":"32968178","tags":["neuropeptides","cardiovascular"],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"Plasma BNP levels increased more than fivefold during therapeutic hypothermia (logarithmically from 1.98 to 2.63, P < 0.01). This was a highly significant change observed across the 21 patients.\n\nDuring cooling, diastolic pulmonary artery pressure actually decreased, and stroke volume index did not change significantly. This means the BNP increase was not driven by the usual triggers of cardiac stress or fluid overload.\n\nIn contrast to BNP, ANP (atrial natriuretic peptide) showed minimal change during cooling. This selective BNP response suggests a specific mechanism linking cold exposure to BNP release from the heart.","whyItMatters":"Doctors use BNP levels to assess heart failure. If therapeutic cooling independently raises BNP, clinicians need to know this to avoid misinterpreting elevated BNP as a sign of worsening heart function in cooled patients.\n\nThe finding also adds to our understanding of how natriuretic peptides respond to temperature, which is relevant to the emerging research on cold exposure and metabolism.","specificNumbers":"21 patients; BNP >5-fold increase (log 1.98→2.63, P<0.01); diastolic PAP decreased; SVI unchanged; ANP minimal change","methodology":"This was an observational study of 21 patients who underwent therapeutic hypothermia after cardiac arrest. Researchers measured plasma BNP and ANP levels along with hemodynamic parameters including pulmonary artery pressure and stroke volume index during the cooling period.","limitations":"This was a small observational study with only 21 patients. There was no control group of cardiac arrest patients who were not cooled.\n\nThe patients were critically ill after cardiac arrest, so other factors beyond temperature could have influenced BNP levels. The mechanism linking cold to BNP release was not directly tested."},{"rthcId":"RPEP-04899","title":"Natriuretic peptides and neprilysin inhibition in hypertension and hypertensive organ damage.","authors":"Kato, Johji","year":2020,"journal":"Peptides, 132, 170352","doi":"10.1016/j.peptides.2020.170352","pmid":"32610060","tags":["neuropeptides","cardiovascular"],"studyType":"review","evidenceStrength":"n/a (review)","keyFinding":"ANP and BNP are released by the heart in response to increased pressure or volume. They lower blood pressure and reduce fluid retention through specific receptors. CNP is produced by blood vessel walls and acts locally to protect blood vessels.\n\nBeyond lowering blood pressure, natriuretic peptides also reduce the organ damage caused by hypertension, including heart enlargement, kidney damage, and blood vessel stiffening.\n\nNeprilysin is the enzyme that degrades natriuretic peptides. Blocking neprilysin with drugs increases the activity of the body's own peptides. A dual inhibitor combining neprilysin inhibition with an angiotensin receptor blocker (sacubitril/valsartan) has been approved for heart failure, and clinical data shows neprilysin inhibition also benefits hypertension patients.","whyItMatters":"High blood pressure is the leading risk factor for heart disease and stroke worldwide. The natriuretic peptide system represents a natural defense mechanism that the body uses to fight elevated blood pressure. Drugs that enhance this system, rather than simply blocking harmful pathways, offer a fundamentally different approach to treatment.\n\nThe approval of sacubitril/valsartan for heart failure has already validated this approach, and expanding its use to hypertension could benefit millions of patients.","specificNumbers":"3 natriuretic peptides (ANP, BNP, CNP); sacubitril/valsartan approved for heart failure; neprilysin inhibition beneficial in hypertension","methodology":"This is a comprehensive review article summarizing basic science and clinical research on natriuretic peptides in blood pressure regulation, hypertensive organ damage, and the therapeutic potential of neprilysin inhibition.","limitations":"As a review article, this does not present new experimental data. The coverage of neprilysin inhibition for hypertension is based on limited clinical data compared to the robust heart failure evidence.\n\nThe review may not include the most recent clinical trial results published after its writing."},{"rthcId":"RPEP-04900","title":"Teriparatide improves pain-related behavior and prevents bone loss in ovariectomized mice.","authors":"Kato, Sho; Wakabayashi, Hiroki; Nakagawa, Taro; Miyamura, Gaku; Naito, Yohei; Iino, Takahiro; Sudo, Akihiro","year":2020,"journal":"Journal of orthopaedic surgery (Hong Kong), 28(1), 2309499019893194","doi":"10.1177/2309499019893194","pmid":"31833446","tags":["neuropeptides","bone-health"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Teriparatide prevents ovariectomy-induced bone loss, reduces mechanical hyperalgesia, and suppresses CGRP and TRPV1 upregulation in dorsal root ganglion neurons innervating affected limbs.","whyItMatters":"Many osteoporosis patients suffer from chronic pain that isn't fully addressed by bone-strengthening drugs. Teriparatide uniquely treats both bone loss and associated pain by modulating neuropeptide signaling.","specificNumbers":"4-week treatment; prevented bone loss on micro-CT; reduced mechanical hyperalgesia; lowered CGRP and TRPV1 expression in DRG neurons","methodology":"Three groups of ovariectomized/sham mice, 4-week subcutaneous teriparatide treatment, von Frey filament mechanical sensitivity testing, microCT bone analysis, immunohistochemistry of DRG neurons.","limitations":"Mouse study with unclear translation to humans. Small group sizes not specified. Only 4 weeks of treatment with no long-term follow-up."},{"rthcId":"RPEP-04901","title":"Antibody-Drug Conjugates Using Mouse-Canine Chimeric Anti-Dog Podoplanin Antibody Exerts Antitumor Activity in a Mouse Xenograft Model.","authors":"Kato, Yukinari; Ito, Yuji; Ohishi, Tomokazu; Kawada, Manabu; Nakamura, Takuro; Sayama, Yusuke; Sano, Masato; Asano, Teizo; Yanaka, Miyuki; Okamoto, Saki; Handa, Saori; Komatsu, Yu; Takei, Junko; Kaneko, Mika K","year":2020,"journal":"Monoclonal antibodies in immunodiagnosis and immunotherapy, 39(2), 37-44","doi":"10.1089/mab.2020.0001","pmid":"32182186","tags":["peptide-drug-development","cancer"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"The antibody-drug conjugate P38B-DM1 was constructed using a mouse-canine chimeric antibody (P38B) that targets dog podoplanin, a peptide linker, and the cytotoxic payload emtansine (DM1). Construction used the chemical conjugation by affinity peptide (CCAP) method.\n\nIn cell culture, P38B-DM1 killed podoplanin-overexpressing cells in a dose-dependent manner. In a mouse xenograft model, P38B-DM1 showed significantly higher anti-tumor activity than the antibody alone (P38B).\n\nThe peptide linker and CCAP conjugation method allowed controlled attachment of the drug to the antibody, which is critical for consistent drug-to-antibody ratios.","whyItMatters":"Antibody-drug conjugates are one of the fastest-growing areas in cancer therapy. Using peptide linkers offers advantages in controlling how and when the drug is released from the antibody.\n\nWhile this specific ADC targets canine cancers (melanoma and squamous cell carcinoma), the CCAP conjugation method and peptide linker technology could be applied to human cancer targets.","specificNumbers":"Dose-dependent cytotoxicity in vitro; higher anti-tumor activity than antibody alone in vivo; CCAP peptide linker conjugation","methodology":"This was a preclinical study. Researchers created the ADC using the CCAP method to conjugate emtansine to the P38B antibody via a peptide linker. Cytotoxicity was tested in vitro against CHO cells overexpressing dog podoplanin. Anti-tumor activity was tested in a mouse xenograft model.","limitations":"The xenograft model used artificially overexpressing cells rather than naturally occurring tumors. Results in natural canine cancers may differ.\n\nThe study focused on a veterinary target (dog podoplanin) and would need separate development for human applications. Safety data was not reported."},{"rthcId":"RPEP-04902","title":"A Randomized, Controlled Trial of Liraglutide for Adolescents with Obesity.","authors":"Kelly, Aaron S; Auerbach, Pernille; Barrientos-Perez, Margarita; Gies, Inge; Hale, Paula M; Marcus, Claude; Mastrandrea, Lucy D; Prabhu, Nandana; Arslanian, Silva","year":2020,"journal":"The New England journal of medicine, 382(22), 2117-2128","doi":"10.1056/NEJMoa1916038","pmid":"32233338","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04903","title":"In Vitro and Ex Vivo Evaluation of Penetratin as a Non-invasive Permeation Enhancer in the Penetration of Salmon Calcitonin through TR146 Buccal Cells and Porcine Buccal Tissues.","authors":"Keum, Taekwang; Noh, Gyubin; Seo, Jo-Eun; Bashyal, Santosh; Lee, Sangkil","year":2020,"journal":"Pharmaceuticals (Basel, Switzerland), 13(11)","doi":"10.3390/ph13110408","pmid":"33233392","tags":["cell-penetrating-peptides","peptide-delivery"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Penetratin enhanced the delivery of salmon calcitonin (sCT) through both TR146 buccal cell layers and porcine buccal tissues in a concentration-dependent manner.\n\nFITC-labeled Penetratin showed rapid intracellular uptake at low concentrations (0-15 micromolar) with a more gradual increase above 15 micromolar. The uptake of sCT increased alongside Penetratin concentration.\n\nAt 12.2 micromolar, Penetratin enhanced sCT flux 5.5-fold through TR146 cell layers and 93.7-fold through porcine buccal tissue. The dramatically higher enhancement in actual tissue suggests Penetratin works particularly well in the multi-layered environment of real buccal mucosa.","whyItMatters":"Many peptide drugs must be injected because they cannot pass through the body's barriers. Buccal (cheek) delivery could replace painful injections with a simple mouth application. Penetratin's dramatic enhancement of calcitonin delivery through cheek tissue suggests it could make this a viable route for large peptide drugs.\n\nA 94-fold improvement in tissue permeation is remarkable and could bring buccal peptide delivery closer to practical use.","specificNumbers":"5.5-fold enhancement (TR146 cells); 93.7-fold enhancement (porcine tissue); 12.2 μM Penetratin","methodology":"This was a laboratory study using TR146 human buccal cancer cell layers and ex vivo porcine buccal tissues. Researchers co-applied fluorescently labeled Penetratin and calcitonin at various concentrations and measured uptake by flow cytometry and confocal microscopy. Permeation through cell layers and tissue was measured in Franz diffusion cells.","limitations":"This was an in vitro and ex vivo study. The porcine tissue results are promising but may not fully predict human buccal permeation. No in vivo testing was performed.\n\nLong-term safety of repeated Penetratin application on buccal tissue was not evaluated."},{"rthcId":"RPEP-04904","title":"Alcohol dependence potentiates substance P/neurokinin-1 receptor signaling in the rat central nucleus of amygdala.","authors":"Khom, S; Steinkellner, T; Hnasko, T S; Roberto, M","year":2020,"journal":"Science advances, 6(12), eaaz1050","doi":"10.1126/sciadv.aaz1050","pmid":"32206720","tags":["neuropeptides","neurological-conditions"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"In normal rats, substance P increased GABA release in the central amygdala, and blocking the NK-1 receptor decreased it. This shows substance P regulates baseline brain activity in this region.\n\nIn alcohol-dependent rats, substance P triggered a larger increase in GABA release despite reduced NK-1 receptor expression. This paradox (fewer receptors but bigger response) indicates receptor hypersensitivity, meaning each remaining receptor was overreacting to substance P.\n\nCritically, the NK-1 receptor antagonist blocked alcohol-induced GABA release in dependent and withdrawn rats but not in normal rats. This means chronic alcohol exposure recruits the substance P system to mediate alcohol's effects on the brain, a mechanism that persists into protracted withdrawal.","whyItMatters":"Understanding why alcohol-dependent brains respond differently to alcohol is key to developing addiction treatments. This study identifies the substance P/NK-1R system as a specific mechanism that changes with chronic alcohol exposure.\n\nBecause the hypersensitivity persists into withdrawal, it could contribute to the anxiety, stress, and craving that drive relapse. NK-1R antagonists, which are already being studied for other conditions, could potentially help treat alcohol use disorder.","specificNumbers":"Increased SP-induced GABA release in dependent rats; decreased NK-1R expression; NK-1R antagonist blocked alcohol effects in dependent but not naive rats; persisted in protracted withdrawal","methodology":"This was an animal neuroscience study using electrophysiology in rat brain slices. Researchers compared GABA transmission in the central amygdala of naive, alcohol-dependent, and withdrawn rats. They applied substance P, an NK-1R antagonist, and acute alcohol to brain slices while recording neural activity. NK-1R expression was measured separately.","limitations":"This was a rat study using brain slice electrophysiology, which removes the brain from its normal environment. The findings may not translate directly to human brains.\n\nThe study focused on one brain region (central amygdala). Substance P signaling in other brain areas may respond differently to chronic alcohol."},{"rthcId":"RPEP-04905","title":"Thymosin β4-Enhancing Therapeutic Efficacy of Human Adipose-Derived Stem Cells in Mouse Ischemic Hindlimb Model.","authors":"Kim, Jong-Ho; Lim, I-Rang; Park, Chi-Yeon; Joo, Hyung Joon; Noh, Ji-Min; Choi, Seung-Cheol; Hong, Soon Jun; Lim, Do-Sun","year":2020,"journal":"International journal of molecular sciences, 21(6)","doi":"10.3390/ijms21062166","pmid":"32245208","tags":["thymosin-beta-4","regenerative-medicine"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Thymosin beta-4 treatment activated human adipose-derived stem cells by upregulating PI3K/AKT/mTOR and MAPK/ERK signaling pathways. It also increased cell migration, sprouting from microbeads, and endothelial differentiation potential.\n\nIn a dorsal window chamber model, the combination of thymosin beta-4 and stem cells produced significantly more microvessel branches than stem cells alone.\n\nIn the ischemic hindlimb model, mice receiving both thymosin beta-4 and stem cells had improved blood flow recovery and less limb or foot loss compared to stem cells alone. This suggests the peptide primes the stem cells to be more effective at building new blood vessels.","whyItMatters":"Stem cell therapy for vascular disease has shown promise but often falls short of expectations. Thymosin beta-4 could be the missing ingredient that activates stem cells to their full potential before or during transplantation.\n\nPeripheral artery disease affects millions of people and can lead to amputation. Improving stem cell therapy with peptide co-treatment could help save more limbs.","specificNumbers":"Upregulated PI3K/AKT/mTOR and MAPK/ERK; increased microvessel branches; improved blood flow; reduced limb loss vs hASCs alone","methodology":"This was a combined in vitro and animal study. Researchers treated human adipose-derived stem cells with thymosin beta-4 and measured signaling pathways, migration, sprouting, and differentiation. In vivo, they transplanted the combination into mice with surgically induced hindlimb ischemia and measured blood flow, vessel formation (dorsal window chamber), and limb survival.","limitations":"This was a mouse study using human stem cells in immune-compromised mice. The immune environment differs significantly from human patients. The study did not report long-term outcomes or whether the benefit was sustained."},{"rthcId":"RPEP-04906","title":"Lactoferricin B like peptide triggers mitochondrial disruption-mediated apoptosis by inhibiting respiration under nitric oxide accumulation in Candida albicans.","authors":"Kim, Suhyun; Hwang, Jae Sam; Lee, Dong Gun","year":2020,"journal":"IUBMB life, 72(7), 1515-1527","doi":"10.1002/iub.2284","pmid":"32267619","tags":["antimicrobial-peptides","peptide-drug-development"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"LBLP triggered endogenous nitric oxide (NO) production in Candida albicans through the NO synthase pathway. This nitric oxide overwhelmed the cell's glutathione defense system, leading to nitrosative stress.\n\nThe excess NO inhibited mitochondrial respiration and altered NAD+/NADH ratios. This disrupted the mitochondrial membrane potential, caused calcium homeostasis failure, and led to mitochondrial superoxide accumulation.\n\nThe cascade ultimately triggered apoptosis (programmed cell death) in the fungal cells. When researchers blocked NO production, all of these effects were reduced, confirming that NO is the central mechanism of LBLP's antifungal action.","whyItMatters":"Fungal infections are increasingly difficult to treat due to drug resistance. Antimicrobial peptides from natural sources like venoms offer a different mechanism of action that fungi may not easily develop resistance to.\n\nUnderstanding exactly how LBLP kills fungi (through the NO pathway) could help researchers design better antifungal peptides or combination therapies.","specificNumbers":"23-amino-acid peptide; NO-dependent killing; decreased glutathione; disrupted mitochondrial respiration and membrane potential; triggered apoptosis","methodology":"This was a laboratory study using Candida albicans cultures. Researchers measured intracellular NO levels, glutathione, mitochondrial respiration, NAD+/NADH ratios, mitochondrial membrane potential, calcium levels, superoxide production, and apoptosis markers. They used NO synthase inhibitors to confirm the NO-dependent mechanism.","limitations":"This was entirely an in vitro study. Whether LBLP can reach Candida infections in a living body, and whether it is safe for human cells at effective concentrations, is unknown.\n\nThe peptide comes from centipede venom, which may require significant modification for therapeutic use."},{"rthcId":"RPEP-04907","title":"Feasibility of dendritic cell-based vaccine against glioblastoma by using cytoplasmic transduction peptide (CTP)-fused protein antigens combined with anti-PD1.","authors":"Kim, Young-Hee; Tran, Thi-Anh-Thuy; Duong, Thi-Hoang-Oanh; Jung, Shin; Kim, In-Young; Moon, Kyung-Sub; Jang, Woo-Youl; Lee, Hyun-Ju; Lee, Je-Jung; Jung, Tae-Young","year":2020,"journal":"Human vaccines & immunotherapeutics, 16(11), 2840-2848","doi":"10.1080/21645515.2020.1732165","pmid":"32401608","tags":["cell-penetrating-peptides","cancer","peptide-vaccines"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Dendritic cells pulsed with CTP-fused tumor antigens (WT1 and BIRC5) showed enhanced expression of MHC molecules and co-stimulatory markers, indicating better antigen presentation. The vaccine also shifted immune signaling toward Th1 cytokine polarization, which favors anti-tumor immunity.\n\nThe CTP-fused antigen approach increased the number of IFN-gamma-producing effector T cells. These T cells showed enhanced killing of glioblastoma target cells expressing the matching antigens.\n\nCombining the vaccine with PD-1 blockade further improved the cytotoxic T lymphocyte response, suggesting the two approaches work better together than either alone.","whyItMatters":"Glioblastoma is the deadliest brain cancer with a median survival of about 15 months. Current treatments rarely provide long-term control. A vaccine that effectively trains the immune system to recognize and kill glioblastoma cells could extend survival.\n\nThe CTP fusion approach solves a key problem in vaccine design by keeping the antigen in the cytoplasm where it can be processed and presented to killer T cells more effectively.","specificNumbers":"Enhanced MHC/co-stimulatory markers; Th1 polarization; increased IFN-gamma+ T cells; enhanced GBM cell lysis; PD-1 blockade additive","methodology":"This was an in vitro study. Researchers confirmed WT1, BIRC5, and PDL1 expression on glioblastoma cells by western blot. They pulsed mature dendritic cells with CTP-fused protein antigens and characterized them by flow cytometry and ELISA. Cytotoxic T lymphocyte activity was measured by IFN-gamma ELISPOT and lactate dehydrogenase release assays.","limitations":"This was entirely an in vitro study. No animal models or patient data were included. Whether this approach would work against glioblastoma in a living brain, with its immune-suppressive environment, is unknown.\n\nThe study did not test whether CTP-fused antigens would work with naturally occurring, patient-derived dendritic cells."},{"rthcId":"RPEP-04908","title":"Human β-Defensin 2 Mediated Immune Modulation as Treatment for Experimental Colitis.","authors":"Koeninger, Louis; Armbruster, Nicole S; Brinch, Karoline Sidelmann; Kjaerulf, Søren; Andersen, Birgitte; Langnau, Carolin; Autenrieth, Stella E; Schneidawind, Dominik; Stange, Eduard F; Malek, Nisar P; Nordkild, Peter; Jensen, Benjamin A H; Wehkamp, Jan","year":2020,"journal":"Frontiers in immunology, 11, 93","doi":"10.3389/fimmu.2020.00093","pmid":"32076420","tags":["antimicrobial-peptides","gut-health","inflammation"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"Systemically administered recombinant hBD2 showed therapeutic efficacy in three distinct colitis models: DSS-induced mucosal injury, TNBS-induced loss of mucosal tolerance, and T-cell transfer colitis. In all three models, hBD2 reduced inflammation, improved disease activity index, and prevented colitis-induced weight loss.\n\nThe effectiveness matched anti-TNF-alpha treatment and steroids, which are current standard-of-care therapies for inflammatory bowel disease.\n\nMechanistically, hBD2 targeted dendritic cells through the CCR2 receptor. It decreased NF-kB phosphorylation (the main inflammatory switch) and increased CREB phosphorylation in these cells, effectively reprogramming them from pro-inflammatory to anti-inflammatory. This is the first study showing in vivo efficacy of a systemically administered defensin.","whyItMatters":"Inflammatory bowel disease (IBD) affects millions of people, and current treatments like anti-TNF drugs have significant side effects and stop working over time. A naturally occurring defensin peptide that matches their effectiveness could represent an entirely new class of IBD therapy.\n\nThe fact that hBD2 worked across three different colitis models, each representing a different disease mechanism, suggests it could be broadly effective rather than limited to one type of IBD.","specificNumbers":"Effective in 3 models (DSS, TNBS, T-cell transfer); matched anti-TNF-α and steroids; targeted DCs via CCR2; first systemic defensin in vivo","methodology":"Researchers tested recombinant hBD2 in three mouse colitis models: DSS (chemical injury), TNBS (immune-mediated), and T-cell transfer. They also treated LPS-activated human blood cells with hBD2 to study the mechanism. Flow cytometry identified dendritic cells as the target. Signaling was analyzed through NF-kB and CREB phosphorylation, and CCR2 dependence was confirmed.","limitations":"These were mouse models of colitis, which do not perfectly replicate human IBD. The optimal dosing, frequency, and route of administration for humans are unknown.\n\nLong-term safety of systemic defensin administration was not assessed. As a peptide, hBD2 would likely need injection rather than oral administration."},{"rthcId":"RPEP-04909","title":"Effect of short- and long-term protein consumption on appetite and appetite-regulating gastrointestinal hormones, a systematic review and meta-analysis of randomized controlled trials.","authors":"Kohanmoo, Ali; Faghih, Shiva; Akhlaghi, Masoumeh","year":2020,"journal":"Physiology & behavior, 226, 113123","doi":"10.1016/j.physbeh.2020.113123","pmid":"32768415","tags":["glp-1-receptor-agonists","weight-loss","gut-health","bioactive-peptides"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Across 49 acute studies, protein significantly reduced hunger (-7 mm on visual scale, P<0.001), desire to eat (-5 mm, P=0.045), and prospective food consumption (-5 mm, P=0.001). It increased fullness (+10 mm, P<0.001) and satiety (+4 mm, P<0.001).\n\nFor gut hormones, protein decreased ghrelin (-20 pg/mL, P<0.001) and increased both cholecystokinin (+30 pg/mL, P<0.001) and GLP-1 (+21 ng/mL, P<0.001). Peptide YY and GIP were not significantly affected.\n\nThere was a dose threshold: appetite feelings changed at doses under 35 grams, but the hormonal changes (ghrelin, CCK, GLP-1) only became significant at 35 grams or more. Long-term protein intake showed no consistent effects except a decrease in GLP-1.","whyItMatters":"Understanding the minimum protein dose needed to trigger hormonal satiety signals is directly useful for designing weight loss diets. The 35-gram threshold for hormone changes gives a practical target for meal planning.\n\nThe finding that long-term protein intake does not sustain the same hormonal benefits seen acutely raises important questions about whether the body adapts to high-protein diets over time.","specificNumbers":"49 acute + 19 long-term studies; hunger -7mm (P<0.001); fullness +10mm (P<0.001); ghrelin -20 pg/mL; CCK +30 pg/mL; GLP-1 +21 ng/mL; 35g hormone threshold","methodology":"This was a systematic review and meta-analysis of randomized controlled trials. Researchers included 49 acute and 19 long-term studies involving healthy adults receiving isocaloric meals. They used random-effects models to calculate mean differences and 95% confidence intervals.","limitations":"The included studies varied in protein sources, timing, and participant characteristics, which introduces heterogeneity. The distinction between 'acute' and 'long-term' effects depends on study duration, which varied.\n\nThe meta-analysis could not determine whether specific protein sources (whey, casein, plant-based) differ in their hormonal effects."},{"rthcId":"RPEP-04910","title":"The Implication of Gut Hormones in the Regulation of Energy Homeostasis and Their Role in the Pathophysiology of Obesity.","authors":"Koliaki, Chrysi; Liatis, Stavros; Dalamaga, Maria; Kokkinos, Alexander","year":2020,"journal":"Current obesity reports, 9(3), 255-271","doi":"10.1007/s13679-020-00396-9","pmid":"32647952","tags":["glp-1-receptor-agonists","obesity","weight-loss","gut-health"],"studyType":"review","evidenceStrength":"n/a (review)","keyFinding":"Combining multiple gut peptide receptor agonists (dual or triple) produces additive weight loss and glycemic improvement, replicating the hormonal changes seen after bariatric surgery.","whyItMatters":"Understanding why gut hormones change in obesity and after weight loss explains both why diets fail and why bariatric surgery succeeds, guiding development of next-generation weight loss drugs.","specificNumbers":"Covers ghrelin, GLP-1, PYY, GIP, CCK, oxyntomodulin changes in obesity and post-surgery; dual/triple agonists in early trials","methodology":"Narrative review of published literature on gut hormone physiology, adaptations in obesity, and emerging pharmacological therapies.","limitations":"Narrative review without systematic methodology. Many dual/triple agonist data cited were from early-phase trials."},{"rthcId":"RPEP-04911","title":"Pentadecapeptide BPC 157 resolves Pringle maneuver in rats, both ischemia and reperfusion.","authors":"Kolovrat, Marijan; Gojkovic, Slaven; Krezic, Ivan; Malekinusic, Dominik; Vrdoljak, Borna; Kasnik Kovac, Katarina; Kralj, Tamara; Drmic, Domagoj; Barisic, Ivan; Horvat Pavlov, Katarina; Petrovic, Andreja; Duzel, Antonija; Knezevic, Mario; Mirkovic, Ivan; Kokot, Antonio; Boban Blagaic, Alenka; Seiwerth, Sven; Sikiric, Predrag","year":2020,"journal":"World journal of hepatology, 12(5), 184-206","doi":"10.4254/wjh.v12.i5.184","pmid":"32547687","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04912","title":"Impact of the Endosomal Escape Activity of Cell-Penetrating Peptides on the Endocytic Pathway.","authors":"Kondow-McConaghy, Helena M; Muthukrishnan, Nandhini; Erazo-Oliveras, Alfredo; Najjar, Kristina; Juliano, Rudolph L; Pellois, Jean-Philippe","year":2020,"journal":"ACS chemical biology, 15(9), 2355-2363","doi":"10.1021/acschembio.0c00319","pmid":"32786263","tags":["cell-penetrating-peptides","peptide-delivery"],"studyType":"in vitro","evidenceStrength":"moderate","keyFinding":"Cell-penetrating peptides must escape endosomes to deliver cargo to the cytoplasm. The researchers found that some CPP delivery protocols activate three cellular stress responses: Chmp1b (endosomal repair), Galectin-3 (organelle clearance), and TFEB (biogenesis).\n\nThese same protocols also modulated endocytosis rates and endocytic proteolysis, suggesting that some CPPs disrupt normal cell trafficking.\n\nRemarkably, a multimeric analogue of TAT (the most commonly used CPP) achieved efficient endosomal escape without triggering any of these membrane damage responses. This challenges the assumption that endosomal leakiness equals toxicity and shows that clean cytoplasmic delivery is achievable.","whyItMatters":"Cell-penetrating peptides are widely used in research and drug development, but concerns about their effects on cell health have limited clinical translation. Showing that efficient delivery is possible without cellular damage removes a major objection to CPP-based therapeutics.\n\nThe multimeric TAT variant could become a preferred delivery vehicle for peptide and protein drugs.","specificNumbers":"Some CPPs activated Chmp1b, Galectin-3, TFEB; multimeric TAT escaped without damage; modulated endocytosis and proteolysis","methodology":"This was a cell biology study using live human cells. Researchers measured activation of Chmp1b, Galectin-3, and TFEB as markers of endosomal damage responses. They compared multiple CPP-based delivery protocols and assessed effects on endocytosis and endocytic proteolysis using fluorescent assays and microscopy.","limitations":"This was a cell culture study. Whether the clean endosomal escape of multimeric TAT translates to in vivo delivery without off-target effects is unknown.\n\nThe study focused on a limited set of CPPs and delivery conditions. Other CPP variants may behave differently."},{"rthcId":"RPEP-04913","title":"Probiotics and oxytocin nasal spray as neuro-social-behavioral interventions for patients with autism spectrum disorders: a pilot randomized controlled trial protocol.","authors":"Kong, Xue-Jun; Liu, Jun; Li, Jing; Kwong, Kenneth; Koh, Madelyn; Sukijthamapan, Piyawat; Guo, Jason J; Sun, Zhenyu Jim; Song, Yiqing","year":2020,"journal":"Pilot and feasibility studies, 6, 20","doi":"10.1186/s40814-020-0557-8","pmid":"32082606","tags":["oxytocin","gut-health","neurological-conditions"],"studyType":"trial protocol","evidenceStrength":"n/a (protocol only)","keyFinding":"This is a protocol for a two-stage pilot randomized controlled trial. In stage one (weeks 0-12), 60 ASD patients receive either oral L. reuteri probiotics or placebo. In stage two (weeks 13-24), all participants also receive intranasal oxytocin spray.\n\nPrimary outcomes include serum oxytocin levels, social behavior scores (Autism Behavior Checklist, Social Responsiveness Scale), an emotional facial matching test, and eye-tracking. Secondary outcomes include GI function, gut microbiome composition, and short-chain fatty acid levels.\n\nThe rationale is based on animal studies showing L. reuteri increases oxytocin levels and improves social behavior in ASD mouse models. Intranasal oxytocin has shown some promise in improving social functioning in ASD patients.","whyItMatters":"Autism spectrum disorder has no FDA-approved treatments targeting core social deficits. Both oxytocin and gut-brain interventions are promising but understudied. This trial is innovative because it tests whether a probiotic can boost the body's own oxytocin production and whether combining it with intranasal oxytocin produces additive benefits.\n\nThe gut-brain-behavior connection in autism is a rapidly growing research area.","specificNumbers":"60 participants; 24 weeks; 2-stage design; probiotics for 24 weeks, oxytocin added at week 13","methodology":"This is a trial protocol, not a results paper. The design is a two-stage, randomized, double-blind, placebo-controlled, parallel-group pilot study. Sixty participants with ASD will be enrolled. Outcomes are assessed at baseline, week 12, and week 24.","limitations":"This is a protocol paper, not a results paper. The trial had not yet reported outcomes at the time of publication. As a pilot study with 60 participants, it is designed to test feasibility rather than prove efficacy.\n\nThe two-stage design means the probiotic effect cannot be fully separated from the oxytocin effect in the second stage."},{"rthcId":"RPEP-04914","title":"Neurobiology of Opioid Addiction: Opponent Process, Hyperkatifeia, and Negative Reinforcement.","authors":"Koob, George F","year":2020,"journal":"Biological psychiatry, 87(1), 44-53","doi":"10.1016/j.biopsych.2019.05.023","pmid":"31400808","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04915","title":"RNase 7 Promotes Sensing of Self-DNA by Human Keratinocytes and Activates an Antiviral Immune Response.","authors":"Kopfnagel, Verena; Dreyer, Sylvia; Baumert, Kathrin; Stark, Maximilian; Harder, Jürgen; Hofmann, Karsten; Kleine, Michael; Buch, Anna; Sodeik, Beate; Werfel, Thomas","year":2020,"journal":"The Journal of investigative dermatology, 140(8), 1589-1598.e3","doi":"10.1016/j.jid.2019.09.029","pmid":"31978413","tags":["antimicrobial-peptides","immune-function"],"studyType":"in vitro","evidenceStrength":"moderate","keyFinding":"RNase 7 combined with human self-DNA strongly induced IP-10 production in keratinocytes. Notably, two other antimicrobial peptides (human beta-defensin 2 and LL-37) combined with DNA did not produce this effect, showing RNase 7 has a unique ability.\n\nThe IP-10 production was mediated through type I interferon (IFN-beta) induction and the STING pathway (stimulator of interferon genes). Blocking the interferon receptor or STING significantly reduced the response.\n\nPretreating keratinocytes with RNase 7 and DNA significantly reduced herpes simplex virus-1 infection, demonstrating a direct antiviral protective function. RNase 7 functions as an alarmin that converts self-DNA into a danger signal activating innate antiviral immunity directly in skin cells.","whyItMatters":"This reveals a new immune function for RNase 7 beyond its known ability to kill bacteria. By helping skin cells recognize their own DNA as a danger signal, RNase 7 activates a built-in antiviral defense system. This could be important for understanding how skin resists viral infections like herpes.\n\nThe STING pathway activation is particularly interesting because it connects an antimicrobial peptide to one of the body's most important antiviral sensing mechanisms.","specificNumbers":"RNase 7 + DNA induced IP-10 via IFN-beta/STING; hBD2 and LL-37 did not; significantly reduced HSV-1 infection","methodology":"This was a cell biology study using human keratinocyte cultures. Researchers stimulated keratinocytes with RNase 7 and human DNA, measuring IP-10 and IFN-beta production. They used blocking antibodies against the interferon receptor and STING pathway inhibitors. Antiviral activity was tested using herpes simplex virus-1 infection of keratinocytes.","limitations":"This was a cell culture study. Whether RNase 7 activates the same antiviral pathway in intact human skin is unknown. The herpes virus protection was shown in pretreated cells, which may not reflect natural infection dynamics.\n\nThe study did not test whether RNase 7 protects against other viruses beyond HSV-1."},{"rthcId":"RPEP-04916","title":"Plant defensin expression triggered by fungal pathogen invasion depends on EDR1 protein kinase and ORA59 transcription factor in Arabidopsis thaliana.","authors":"Kosaka, Ayumi; Suemoto, Haruka; Singkaravanit-Ogawa, Suthitar; Takano, Yoshitaka","year":2020,"journal":"Plant signaling & behavior, 15(12), 1823120","doi":"10.1080/15592324.2020.1823120","pmid":"32985920","tags":["antimicrobial-peptides"],"studyType":"in vitro","evidenceStrength":"moderate","keyFinding":"Multiple plant defensin (PDF) genes were strongly induced in Arabidopsis when the fungal pathogen Colletotrichum tropicale invaded plant cells. A necrotrophic pathogen, Alternaria brassicicola, also triggered PDF expression upon invasion.\n\nIn edr1 mutant plants, defensin expression after pathogen invasion was significantly reduced, showing that EDR1 protein kinase is required for this defense response. Similarly, ora59 mutant plants failed to properly induce defensin expression after invasion.\n\nInoculation assays with A. brassicicola showed that ORA59 is directly involved in post-invasion resistance. Plants lacking ORA59 were more susceptible to the fungal pathogen, linking defensin expression to actual disease resistance.","whyItMatters":"Understanding how plants activate their defensin immune system could help develop crops with stronger disease resistance. The EDR1-ORA59-defensin pathway represents a specific genetic target for improving plant immunity against fungal diseases, which cause billions of dollars in crop losses annually.","specificNumbers":"Multiple PDF genes induced upon invasion; edr1 and ora59 mutants had reduced defensin expression; ora59 mutants more susceptible to A. brassicicola","methodology":"This was a plant biology study using Arabidopsis thaliana. Researchers used wild-type, edr1 mutant, and ora59 mutant plants infected with two fungal pathogens. Defensin gene expression was measured by quantitative methods. Disease resistance was assessed through pathogen inoculation assays.","limitations":"This study used the model plant Arabidopsis, which may not perfectly represent defensin regulation in crop plants. The specific pathogens tested may trigger different responses than field pathogens.\n\nThe study focused on two regulatory proteins but did not fully map the signaling pathway connecting pathogen detection to defensin gene activation."},{"rthcId":"RPEP-04917","title":"Disulfide linked hetero dimeric peptide arrays for screening functional peptides inside cells.","authors":"Kozaki, Ikko; Shimizu, Kazunori; Honda, Hiroyuki","year":2020,"journal":"Journal of bioscience and bioengineering, 129(5), 613-618","doi":"10.1016/j.jbiosc.2019.11.012","pmid":"31839388","tags":["cell-penetrating-peptides","peptide-drug-development"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"The team developed heterodimeric peptide arrays where a cell-penetrating peptide (CPP) and a functional peptide are linked by a disulfide bond. Inside cells, the reducing environment breaks this bond, releasing the functional peptide to act independently.\n\nThe synthesis method used Fmoc-Lys(ivDde)-OH to build both peptides on a single molecule and selectively form the disulfide bond. This enabled efficient production of CPP-functional peptide heterodimers.\n\nUsing this system to screen single amino acid substitutions of a cell-death-inducing peptide (WELVVLGKL), they identified 6 variants with higher activity than the original. This demonstrates the system's utility for optimizing intracellular peptide functions.","whyItMatters":"A major problem in peptide drug discovery is that the cell-penetrating peptide needed for delivery can interfere with the test peptide's activity. This cleavable linker system solves that problem, allowing researchers to find active peptides without delivery-related artifacts.\n\nThe approach could accelerate discovery of intracellular peptide therapeutics.","specificNumbers":"Disulfide-linked heterodimers; Fmoc-Lys(ivDde)-OH synthesis; 6 improved variants of WELVVLGKL cell-death peptide","methodology":"This was a peptide chemistry and cell biology study. Researchers synthesized CPP-functional peptide heterodimers with cleavable disulfide bonds. They screened a single amino acid substitution library of a cell-death-inducing peptide in cell-based assays.","limitations":"The system was demonstrated with a single peptide library. Its applicability to diverse peptide types and cellular activities needs further validation.\n\nThe disulfide bond may not be stable in all cell types or conditions, potentially limiting the system's generalizability."},{"rthcId":"RPEP-04918","title":"Innate Immune Dysfunction in Rosacea Promotes Photosensitivity and Vascular Adhesion Molecule Expression.","authors":"Kulkarni, Nikhil N; Takahashi, Toshiya; Sanford, James A; Tong, Yun; Gombart, Adrian F; Hinds, Brian; Cheng, Joyce Y; Gallo, Richard L","year":2020,"journal":"The Journal of investigative dermatology, 140(3), 645-655.e6","doi":"10.1016/j.jid.2019.08.436","pmid":"31472105","tags":["antimicrobial-peptides","inflammation"],"studyType":"in vitro","evidenceStrength":"moderate","keyFinding":"Dermal endothelial cells in rosacea showed increased VCAM1 expression. The researchers found that UVB-exposed keratinocytes produced double-stranded RNA that, in the presence of LL-37, induced adhesion molecules on endothelial cells.\n\nSequencing revealed activation of pathways directly relevant to rosacea: type I and II interferon signaling, cell-cell adhesion, leukocyte chemotaxis, and angiogenesis.\n\nThe double-stranded RNA + LL-37 combination promoted monocyte adhesion and transmigration across endothelial cell layers. Knocking down TLR3, RIGI, or IRF1 reduced monocyte adhesion, confirming the RNA recognition pathway is the key mechanism.","whyItMatters":"Rosacea affects about 5% of the global population, and sun sensitivity is one of its most troublesome features. This study provides a molecular explanation: the excess LL-37 in rosacea skin converts normal UV exposure into an inflammatory signal that activates blood vessels.\n\nUnderstanding this mechanism could lead to targeted treatments that block the LL-37/RNA interaction rather than broadly suppressing inflammation.","specificNumbers":"LL-37 + dsRNA induced VCAM1; activated IFN/adhesion/chemotaxis/angiogenesis pathways; TLR3/RIGI/IRF1 knockdown reduced response","methodology":"This was a cell biology study using human keratinocytes, dermal microvascular endothelial cells, and monocytes. Researchers exposed keratinocytes to UVB, analyzed RNA content, and tested endothelial responses to LL-37 + RNA combinations. RNA sequencing, gene knockdown, and monocyte migration assays were used.","limitations":"This was a cell culture study that cannot fully replicate the complex skin environment. The relative contributions of LL-37 and other factors to rosacea photosensitivity in actual patients remain to be determined.\n\nThe study used a synthetic RNA rather than natural UV-induced RNA for some experiments."},{"rthcId":"RPEP-04919","title":"PEGylation and Cell-Penetrating Peptides: Glimpse into the Past and Prospects in the Future.","authors":"Kumar, Sumit; Singh, Devender; Kumari, Pooja; Malik, Rajender Singh; Poonam; Parang, Keykavous; Tiwari, Rakesh Kumar","year":2020,"journal":"Current topics in medicinal chemistry, 20(5), 337-348","doi":"10.2174/1568026620666200128142603","pmid":"31994461","tags":["cell-penetrating-peptides","peptide-delivery","peptide-drug-development"],"studyType":"review","evidenceStrength":"n/a (review)","keyFinding":"Many drugs fail because they are broken down too quickly by enzymes or cannot get inside cells where they need to work. PEGylation addresses the first problem by shielding molecules from degradation and kidney clearance. CPPs address the second by ferrying cargo across cell membranes.\n\nHowever, CPPs themselves are peptides and suffer from rapid degradation. PEGylating CPPs can protect them while preserving their cell-penetrating ability.\n\nThe review covers PEGylated CPP formulations used in drug delivery for cancer, gene therapy, protein delivery, and other biomedical applications. It discusses the trade-offs between PEG chain length, CPP type, and overall delivery efficiency.","whyItMatters":"Drug delivery is often the bottleneck in getting effective therapies to patients. Combining two proven strategies (PEGylation and CPPs) into a single system is a practical approach that is already being applied across multiple therapeutic areas.\n\nUnderstanding how to balance PEG shielding with CPP activity is critical for designing the next generation of peptide-based drug delivery systems.","specificNumbers":"Covers PEGylated CPP formulations through Aug 2019; multiple therapeutic applications reviewed","methodology":"This is a review article summarizing published research on PEGylated cell-penetrating peptide systems for drug delivery through August 2019.","limitations":"As a review, this does not present new data. The field moves quickly, and formulations described may have been superseded by newer approaches since publication.\n\nThe review notes that PEG can sometimes interfere with CPP function, and optimizing the balance is still an active area of research."},{"rthcId":"RPEP-04920","title":"Native/citrullinated LL37-specific T-cells help autoantibody production in Systemic Lupus Erythematosus.","authors":"Lande, R; Palazzo, R; Gestermann, N; Jandus, C; Falchi, M; Spadaro, F; Riccieri, V; James, E A; Butera, A; Boirivant, M; Feldmeyer, L; Surbeck, I; Di Lucca, J; Stuber, F; Spinelli, F R; Botti, E; Marinari, B; Bianchi, L; Pica, R; Cerbelli, B; Giannakakis, K; Auteri, S E; Daniels, I; Durrant, L G; Horstman, S; Costanzo, A; Romero, P; Alessandri, C; Conti, F; Valesini, G; Gilliet, M; Chizzolini, C; Frasca, L","year":2020,"journal":"Scientific reports, 10(1), 5851","doi":"10.1038/s41598-020-62480-3","pmid":"32245990","tags":["antimicrobial-peptides","immune-function","inflammation"],"studyType":"human observational","evidenceStrength":"moderate","keyFinding":"45% of SLE patients had circulating T cells that responded strongly to LL37. These T cell levels correlated with anti-LL37 antibody levels and disease activity.\n\nUnlike psoriasis, where LL37-specific T cells are Th17 cells, the SLE LL37-specific T cells displayed a T-follicular helper (TFH)-like phenotype with CXCR5, Bcl-6, and IL-21 expression. This profile is designed to help B cells produce antibodies.\n\nCitrullinated LL37 (cit-LL37) was found abundantly in SLE tissues (skin and kidney). SLE T cells showed much stronger reactivity to cit-LL37 compared to native LL37. In functional assays, these T cells promoted B cell secretion of pathogenic anti-LL37 antibodies.","whyItMatters":"This study reveals that the same autoantigen (LL37) drives different immune responses depending on the disease. In psoriasis, it triggers inflammation through Th17 cells. In lupus, it drives autoantibody production through follicular helper T cells. Understanding this distinction could lead to disease-specific treatments.\n\nThe strong reactivity to citrullinated LL37 suggests that post-translational modifications of self-proteins are important triggers for lupus autoimmunity.","specificNumbers":"45% had LL37-reactive T cells; TFH phenotype (CXCR5+/Bcl-6+/IL-21+); stronger cit-LL37 reactivity; correlated with antibodies and disease activity","methodology":"Researchers analyzed blood samples from SLE patients for LL37-reactive T cells using flow cytometry and functional assays. They characterized T cell phenotype (TFH markers), tested reactivity to native vs citrullinated LL37, and performed B cell co-culture assays to measure antibody production. Tissue samples were analyzed for cit-LL37 presence.","limitations":"The study shows association between LL37-reactive T cells and disease activity but cannot prove causation. It is unclear whether these T cells drive disease or are a consequence of it.\n\nThe sample sizes for SLE patient subgroup analyses were not detailed in the abstract."},{"rthcId":"RPEP-04921","title":"Generation of Monoclonal Antibodies Specific for Native LL37 and Citrullinated LL37 That Discriminate the Two LL37 Forms in the Skin and Circulation of Cutaneous/Systemic Lupus Erythematosus and Rheumatoid Arthritis Patients.","authors":"Lande, Roberto; Palazzo, Raffaella; Hammel, Philippe; Pietraforte, Immacolata; Surbeck, Isabelle; Gilliet, Michel; Chizzolini, Carlo; Frasca, Loredana","year":2020,"journal":"Antibodies (Basel, Switzerland), 9(2)","doi":"10.3390/antib9020014","pmid":"32403306","tags":["antimicrobial-peptides","immune-function"],"studyType":"tool development","evidenceStrength":"moderate","keyFinding":"Six recombinant antibodies (MRB137-MRB142) were produced as monovalent mouse antibodies with scFv portions fused to mouse IgG2a Fc. These antibodies can specifically recognize either native LL37 or citrullinated LL37 and do not cross-react with carbamylated LL37.\n\nUsing ELISA, the antibodies detected native LL37 or citrullinated LL37 in serum samples from SLE and rheumatoid arthritis patients. Immunohistochemistry detected these forms in skin tissue from cutaneous lupus patients.\n\nThese antibodies are previously unavailable tools that can now be used to study the relationship between post-translationally modified LL37 and immune system activation in chronic autoimmune diseases.","whyItMatters":"Modified forms of LL37 are increasingly recognized as important in autoimmune diseases, but until now there were no antibodies that could reliably tell them apart. These tools will enable researchers to study which form of LL37 is present in different diseases and tissues, potentially leading to better biomarkers and targeted therapies.","specificNumbers":"6 antibodies (MRB137-142); native vs cit-LL37 discrimination; ELISA + IHC validation in SLE, RA, cutaneous lupus","methodology":"Researchers generated recombinant antibodies using phage display, produced them as scFv-Fc fusions, and characterized their specificity against native, citrullinated, and carbamylated LL37. They tested the antibodies in ELISA with patient sera and immunohistochemistry on lupus skin tissue.","limitations":"This is a tool development paper. The antibodies' diagnostic utility and clinical value need to be validated in larger patient cohorts.\n\nThe study did not determine whether the levels of native vs citrullinated LL37 predict disease activity or treatment response."},{"rthcId":"RPEP-04922","title":"Fully automated dried blood spot sample preparation enables the detection of lower molecular mass peptide and non-peptide doping agents by means of LC-HRMS.","authors":"Lange, Tobias; Thomas, Andreas; Walpurgis, Katja; Thevis, Mario","year":2020,"journal":"Analytical and bioanalytical chemistry, 412(15), 3765-3777","doi":"10.1007/s00216-020-02634-4","pmid":"32300840","tags":["peptide-drug-development","growth-hormone-peptides","regulatory"],"studyType":"method development","evidenceStrength":"n/a (analytical method)","keyFinding":"The method combined robotic-assisted near-infrared hematocrit measurement with fully automated strong cation exchange solid-phase extraction. This enabled detection of 46 lower molecular mass (<2 kDa) peptide and non-peptide doping agents by LC-HRMS.\n\nTarget analytes included agonists of the gonadotropin-releasing hormone receptor, ghrelin receptor, growth hormone receptor, and antidiuretic hormone receptor. Several glycine derivatives of GHRPs, designed to evade current testing, were also covered.\n\nValidation met WADA guidelines with LODs between 0.5 and 20 ng/mL. Proof of concept was demonstrated with authentic post-administration samples containing GHRP-2 and GHRP-6. The method also worked with blood collected by microneedle devices from the upper arm.","whyItMatters":"Dried blood spots are increasingly used in doping control because they are easy to collect and transport. This automated method makes peptide doping detection faster and more reliable, while also catching designer peptides that were specifically made to avoid current tests.\n\nThe microneedle compatibility means athletes could be tested with a nearly painless arm device instead of traditional blood draws.","specificNumbers":"46 analytes; LODs 0.5-20 ng/mL; WADA-validated; GHRP-2/GHRP-6 confirmed in real samples; microneedle DBS compatible","methodology":"This was an analytical method development study. Researchers used robotic near-infrared spectroscopy for hematocrit measurement, automated SPE for sample preparation, and LC-HRMS for detection. Validation followed WADA guidelines. Real post-administration samples and microneedle-collected blood were tested.","limitations":"The method focuses on lower molecular mass peptides (<2 kDa) and would not detect larger protein-based doping agents like EPO or growth hormone directly.\n\nLong-term stability of all 46 analytes in dried blood spots was not comprehensively assessed."},{"rthcId":"RPEP-04923","title":"Early immune innate hallmarks and microbiome changes across the gut during Escherichia coli O157: H7 infection in cattle.","authors":"Larzábal, Mariano; Da Silva, Wanderson Marques; Multani, Anmol; Vagnoni, Lucas E; Moore, Dadin P; Marin, Maia S; Riviere, Nahuel A; Delgado, Fernando O; Vilte, Daniel A; Victorica, Matias Romero; Ma, Tao; Le Guan, Luo; Talia, Paola; Cataldi, Angel; Cobo, Eduardo R","year":2020,"journal":"Scientific reports, 10(1), 21535","doi":"10.1038/s41598-020-78752-x","pmid":"33299023","tags":["antimicrobial-peptides","gut-health"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Calves orally inoculated with EHEC O157:H7 showed neutrophil infiltration in the ileum and recto-anal junction at 7 and 14 days post-infection. Mucin layers and mast cell populations were altered across the small and large intestines.\n\nThere were differential expression changes in key bovine beta-defensins: tracheal antimicrobial peptide (TAP) was altered in the ileum, and lingual antimicrobial peptide (LAP) was changed in the recto-anal junction. TLR4, the main receptor for detecting E. coli's lipopolysaccharide, was downregulated in the recto-anal junction.\n\nGut bacterial communities were also affected, with changes in Negativibacillus and Erysipelotrichaceae abundance in rectal mucosa-associated bacteria. All of this occurred without major clinical signs.","whyItMatters":"Cattle carry E. coli O157:H7 without getting sick, but they spread it to humans where it causes severe illness. Understanding how the bacteria interact with cattle gut immunity could help develop strategies to reduce colonization and prevent human outbreaks.\n\nThe TLR4 downregulation in the recto-anal junction suggests the bacteria may actively suppress immune detection at their preferred colonization site.","specificNumbers":"Neutrophil infiltration at d7/d14; altered TAP (ileum), LAP (RAJ); TLR4 downregulated in RAJ; Negativibacillus and Erysipelotrichaceae shifts","methodology":"Calves were orally inoculated with EHEC O157:H7. Researchers collected gut tissue at 7 and 14 days post-infection and analyzed immune cell infiltration, mucin, mast cells, antimicrobial peptide expression, TLR4 expression, and microbiome composition across multiple gut regions.","limitations":"This was a small animal study with limited calf numbers (not specified in abstract). The 14-day follow-up may not capture longer-term immune adaptations.\n\nThe study describes changes but cannot determine whether they are protective or facilitate bacterial persistence."},{"rthcId":"RPEP-04924","title":"Pain modulatory properties of Phoneutria nigriventer crude venom and derived peptides: A double-edged sword.","authors":"Lauria, Pedro Santana Sales; Villarreal, Cristiane Flora; Casais-E-Silva, Luciana Lyra","year":2020,"journal":"Toxicon : official journal of the International Society on Toxinology, 185, 120-128","doi":"10.1016/j.toxicon.2020.07.005","pmid":"32668276","tags":["venom-peptides","pain-management"],"studyType":"review","evidenceStrength":"n/a (review)","keyFinding":"The pain caused by Phoneutria nigriventer venom is mediated through both peripheral and central mechanisms, involving B2 receptors, serotonin (5-HT4), glutamate (NMDA/AMPA), tachykinin (NK1/NK2), sodium channels (TTX-sensitive), acid-sensing channels (ASIC), and TRPV1 channels.\n\nDespite the venom's pain-causing nature, seven individual toxins (omega-CNTX-Pn4a, omega-CNTX-Pn2a, omega-CNTX-Pn3a, kappa-CNTX-Pn1a, U7-CNTX-Pn1a, delta-CNTX-Pn1a, Gamma-CNTX-Pn1a) and a semi-synthetic peptide (PnPP-19) have shown consistent antinociceptive (pain-relieving) properties in experimental pain models.\n\nThe pain-relieving toxins work through mechanisms including calcium channel blockade, potassium channel activation, and modulation of opioid receptors.","whyItMatters":"The opioid crisis has created urgent demand for non-opioid pain medicines. Spider venom toxins that block pain through novel mechanisms could lead to new analgesics without the addiction risk of opioids.\n\nThe fact that multiple pain-relieving peptides exist in a single venom source provides several drug leads to pursue simultaneously.","specificNumbers":"7 antinociceptive toxins + PnPP-19; pain via B2/5-HT4/NMDA/AMPA/NK1/NK2/ASIC/TRPV1; analgesia via Ca2+ channels, K+ channels, opioid receptors","methodology":"This is a review article summarizing published research on the pro-nociceptive and antinociceptive properties of Phoneutria nigriventer venom and its isolated toxins. It covers in vitro mechanism studies and in vivo pain models.","limitations":"This is a review article. The antinociceptive peptides have been tested in animal models but have not entered human clinical trials. Translating venom peptides into safe human medications involves significant challenges including stability, delivery, and side effects.\n\nSome mechanisms described are based on limited studies that need replication."},{"rthcId":"RPEP-04925","title":"The endomorphin-1/2 and dynorphin-B peptides display biased agonism at the mu opioid receptor.","authors":"LaVigne, Justin; Keresztes, Attila; Chiem, Daniel; Streicher, John M","year":2020,"journal":"Pharmacological reports : PR, 72(2), 465-471","doi":"10.1007/s43440-020-00061-x","pmid":"32112361","tags":["neuropeptides","pain-management"],"studyType":"in vitro","evidenceStrength":"moderate","keyFinding":"Endomorphin-1 and endomorphin-2 showed a bias toward cAMP signaling at the mu opioid receptor (MOR), while dynorphin-B showed a bias toward G-protein (35S-GTPgammaS) signaling. This pattern was consistent across multiple cell lines expressing human MOR.\n\nThe researchers investigated whether RGS-4 (a G-protein regulator) or adenylyl cyclase 6 (AC6) might explain the endomorphin bias. However, neither an RGS-4 inhibitor nor AC6 knockdown significantly changed the bias profile, ruling out these specific mechanisms.\n\nBiased agonism at opioid receptors is important because different signaling pathways may lead to different physiological effects. Pain relief, euphoria, respiratory depression, and constipation are thought to be mediated by different downstream pathways.","whyItMatters":"Understanding biased agonism at opioid receptors could help develop pain medications that relieve pain without causing dangerous side effects like respiratory depression. If the body's own peptides already show signaling bias, that bias may be harnessable for drug design.\n\nThe finding that endogenous peptides have built-in bias challenges the simple view that all opioid agonists act the same way at the same receptor.","specificNumbers":"Endomorphin-1/2 cAMP-biased; dynorphin-B G-protein-biased; consistent across 3 cell lines; RGS-4 and AC6 not responsible","methodology":"Researchers used three cell lines (CHO, N2a, SH-SY5Y) expressing human MOR to measure signaling bias between 35S-GTPgammaS binding (G-protein activation) and cAMP assays. They used an RGS-4 selective inhibitor and siRNA knockdown of AC6 in N2a cells to probe mechanisms.","limitations":"This was entirely a cell-based study using overexpression systems, which may not fully reflect signaling in neurons. The functional consequences of the observed bias in terms of pain, reward, or side effects were not tested.\n\nThe mechanisms underlying the bias remain unclear after ruling out RGS-4 and AC6."},{"rthcId":"RPEP-04926","title":"Snake- and Spider-Venom-Derived Toxins as Lead Compounds for Drug Development.","authors":"Lazarovici, Philip","year":2020,"journal":"Methods in molecular biology (Clifton, N.J.), 2068, 3-26","doi":"10.1007/978-1-4939-9845-6_1","pmid":"31576520","tags":["venom-peptides","peptide-drug-development","pain-management"],"studyType":"review","evidenceStrength":"n/a (review)","keyFinding":"Venom-derived peptide toxins possess optimized pharmaceutical properties — high selectivity, potency, protease resistance, and low immunogenicity — making them ideal drug leads with several already approved.","whyItMatters":"Venoms represent a vast, largely untapped library of bioactive peptides that evolution has already optimized for potency and selectivity, accelerating drug discovery.","specificNumbers":"Multiple approved snake venom drugs; spider venom peptides in clinical development; complex disulfide scaffolds; targets include ion channels, receptors, coagulation proteins","methodology":"Narrative review covering venom biochemistry, structural diversity, evolution of toxin scaffolds, and examples of approved and developmental venom-derived drugs.","limitations":"Overview review without systematic methodology. Limited detail on specific clinical trial results."},{"rthcId":"RPEP-04927","title":"Oxytocin Facilitation of Emotional Empathy Is Associated With Increased Eye Gaze Toward the Faces of Individuals in Emotional Contexts.","authors":"Le, Jiao; Kou, Juan; Zhao, Weihua; Fu, Meina; Zhang, Yingying; Becker, Benjamin; Kendrick, Keith M","year":2020,"journal":"Frontiers in neuroscience, 14, 803","doi":"10.3389/fnins.2020.00803","pmid":"32848571","tags":["oxytocin","neurological-conditions"],"studyType":"randomized controlled trial","evidenceStrength":"moderate","keyFinding":"Intranasal oxytocin (24 IU) enhanced emotional empathy responses to both positive and negative emotional stimuli in the Multifaceted Empathy Task, replicating previous findings across multiple cultures.\n\nEye-tracking revealed the mechanism: oxytocin increased the proportion of time participants spent viewing the faces of people in the pictures and decreased time spent viewing body posture and background context.\n\nThis suggests oxytocin does not directly amplify emotional processing. Instead, it redirects visual attention toward the most informative social cue (the face), which naturally leads to stronger empathic responses.","whyItMatters":"Understanding how oxytocin enhances empathy is important for developing it as a potential treatment for social deficits in autism and other conditions. If oxytocin works by redirecting attention to faces rather than directly boosting emotional processing, that has implications for how it might be combined with behavioral therapies.\n\nThe eye-tracking mechanism provides a measurable biomarker for oxytocin's social effects.","specificNumbers":"40 participants; 24 IU oxytocin; enhanced empathy for positive and negative stimuli; increased face viewing time; decreased body/background viewing","methodology":"This was a randomized, placebo-controlled, within-subject experiment. Forty healthy male participants received either intranasal oxytocin (24 IU) or placebo on separate sessions. They completed the Multifaceted Empathy Task while eye-tracking recorded where they looked. The study was registered on ClinicalTrials.gov.","limitations":"This study included only male participants, and oxytocin's effects may differ in women. The sample size of 40, while adequate for a within-subject design, limits generalizability.\n\nThe Multifaceted Empathy Task uses pictures, which may not fully capture empathy in real-world social interactions."},{"rthcId":"RPEP-04928","title":"Engineering of a Potent, Long-Acting NPY2R Agonist for Combination with a GLP-1R Agonist as a Multi-Hormonal Treatment for Obesity.","authors":"Lear, Sam; Pflimlin, Elsa; Zhou, Zhihong; Huang, David; Weng, Sharon; Nguyen-Tran, Van; Joseph, Sean B; Roller, Shane; Peterson, Scott; Li, Jing; Tremblay, Matthew; Schultz, Peter G; Shen, Weijun","year":2020,"journal":"Journal of medicinal chemistry, 63(17), 9660-9671","doi":"10.1021/acs.jmedchem.0c00740","pmid":"32844654","tags":["weight-loss","obesity","glp-1-receptor-agonists","peptide-drug-development"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"The native PYY peptide has a very short half-life, making it impractical as a medication. Using combined peptide stapling and PEG-fatty acid conjugation, the researchers created potent PYY analogs that activate the NPY2 receptor and have rat half-lives exceeding 14 hours.\n\nThe 14-hour rat half-life is expected to translate to a human half-life suitable for once-weekly dosing, which would be practical for patients.\n\nThe lead candidate (compound 22) combined with a long-acting GLP-1 analog showed excellent efficacy in a diet-induced obesity mouse model for three key outcomes: glucose control, food intake reduction, and body weight loss. This combination approach mimics the hormonal changes seen after bariatric surgery.","whyItMatters":"Bariatric surgery increases both GLP-1 and PYY, which likely contributes to its exceptional weight loss results. Recreating this hormonal combination pharmacologically could give patients surgery-level benefits without the risks of an operation.\n\nThe engineering approach (stapling + PEG-fatty acid) is a significant technical achievement that solved PYY's short half-life problem.","specificNumbers":">14h rat half-life; compound 22 + GLP-1 analog; excellent glucose/food intake/weight loss outcomes in DIO mice","methodology":"Researchers used peptide stapling and PEG-fatty acid conjugation to engineer PYY analogs. They measured NPY2R potency, pharmacokinetics in rats, and in vivo efficacy in diet-induced obesity mice. The lead compound was tested alone and in combination with a long-acting GLP-1 analog.","limitations":"This was a mouse study. The predicted human half-life for once-weekly dosing needs to be confirmed in human pharmacokinetic studies.\n\nLong-term efficacy and safety of PYY/GLP-1 combination therapy have not been assessed. The nausea and GI side effects common with gut hormone drugs were not specifically evaluated."},{"rthcId":"RPEP-04929","title":"Recombinant Expression and Stapling of a Novel Long-Acting GLP-1R Peptide Agonist.","authors":"Lear, Sam; Seo, Hyosuk; Lee, Candy; Lei, Lei; Amso, Zaid; Huang, David; Zou, Huafei; Zhou, Zhihong; Nguyen-Tran, Vân T B; Shen, Weijun","year":2020,"journal":"Molecules (Basel, Switzerland), 25(11)","doi":"10.3390/molecules25112508","pmid":"32481528","tags":["glp-1-receptor-agonists","peptide-drug-development","cyclic-peptides"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"A symmetrically stapled exendin-4 analog with an integrated albumin-binding motif showed excellent blood sugar and body weight reduction in diabetic/obese mice.","whyItMatters":"Current GLP-1 drugs require frequent dosing. This stapling strategy could yield once-weekly or even longer-acting peptide therapeutics with simpler manufacturing.","specificNumbers":"Second-gen stapled exendin-4; symmetrical PEG-fatty acid staple; excellent in vivo efficacy; semisynthetic manufacturing protocol","methodology":"Peptide chemistry + animal efficacy study: the linear peptide was recombinantly expressed, then chemically stapled with a PEG-fatty acid cross-linker. Efficacy was tested in a diabetic/obese mouse model.","limitations":"Only tested in an animal model with unspecified group sizes; no pharmacokinetic half-life data reported; human translation remains uncertain."},{"rthcId":"RPEP-04930","title":"Antibacterial action of lactoferricin B like peptide against Escherichia coli: reactive oxygen species-induced apoptosis-like death.","authors":"Lee, B; Hwang, J S; Lee, D G","year":2020,"journal":"Journal of applied microbiology, 129(2), 287-295","doi":"10.1111/jam.14632","pmid":"32145045","tags":["antimicrobial-peptides","peptide-drug-development"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"LBLP kills E. coli through ROS-induced apoptosis-like death rather than membrane disruption, and shows no hemolytic toxicity to human erythrocytes.","whyItMatters":"Antibiotic resistance is a growing global crisis. Peptides with novel killing mechanisms — like triggering bacterial suicide rather than membrane lysis — could yield antibiotics that are harder for bacteria to evolve resistance against.","specificNumbers":"23-mer AMP; potent anti-E. coli activity; no hemolysis; ROS-dependent apoptosis-like death; NAC reversed killing","methodology":"In vitro antibacterial assays against E. coli with mechanistic studies including ROS measurement, membrane depolarization, DNA fragmentation, caspase-like protein activation, and phosphatidylserine exposure. NAC (ROS scavenger) used to confirm mechanism.","limitations":"In vitro only — no animal infection model tested; only tested against E. coli; concentration-dependent toxicity profile not fully characterized."},{"rthcId":"RPEP-04931","title":"Comparative assessment of genotypic and phenotypic correlates of Staphylococcus pseudintermedius strains isolated from dogs with otitis externa and healthy dogs.","authors":"Lee, Gi Yong; Yang, Soo-Jin","year":2020,"journal":"Comparative immunology, microbiology and infectious diseases, 70, 101376","doi":"10.1016/j.cimid.2019.101376","pmid":"31703937","tags":["antimicrobial-peptides"],"studyType":"in vitro","evidenceStrength":"moderate","keyFinding":"S. pseudintermedius from otitis externa cases were more resistant to the canine cathelicidin K9CATH than strains from healthy dogs, despite similar biofilm-forming ability.","whyItMatters":"Understanding how pathogenic bacteria evade natural antimicrobial peptides helps explain why some infections persist and informs development of better veterinary antimicrobial treatments.","specificNumbers":"41 strains; otitis strains more K9CATH-resistant; >95% MRSP had SCCmec V + MDR; high MLST/agr/spa diversity; no biofilm difference","methodology":"Comparative in vitro study of 41 bacterial strains (26 from otitis, 15 from healthy dogs) using multilocus sequence typing, antimicrobial resistance profiling, biofilm assays, and cathelicidin susceptibility testing.","limitations":"Relatively small sample (41 strains); single geographic region (Korea); no in vivo infection model to confirm clinical relevance of K9CATH resistance."},{"rthcId":"RPEP-04932","title":"CCL17 in Inflammation and Pain.","authors":"Lee, Kevin M-C; Jarnicki, Andrew; Achuthan, Adrian; Fleetwood, Andrew J; Anderson, Gary P; Ellson, Christian; Feeney, Maria; Modis, Louise K; Smith, Julia E; Hamilton, John A; Cook, Andrew","year":2020,"journal":"Journal of immunology (Baltimore, Md. : 1950), 205(1), 213-222","doi":"10.4049/jimmunol.2000315","pmid":"32461237","tags":["neuropeptides","pain-management","inflammation"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"A GM-CSF→CCL17 pathway in macrophages drives inflammatory pain through nerve growth factor, CGRP, and substance P signaling in non-bone-marrow-derived cells.","whyItMatters":"Identifying that CCL17 funnels through neuropeptides like CGRP and substance P to cause pain reveals multiple potential drug targets for inflammatory and arthritic pain.","specificNumbers":"CCL17 from macrophages (GM-CSF-dependent); acts on CCR4+ non-BM cells; NGF, CGRP, substance P all required for pain","methodology":"Multiple mouse inflammation and arthritis models using Ccl17 reporter mice, radiation chimeras, and pharmacological blockade of downstream mediators (NGF, CGRP, substance P).","limitations":"Mouse models only; group sizes not specified; the specific CCR4+ non-bone-marrow cells responding to CCL17 were not fully identified."},{"rthcId":"RPEP-04933","title":"Antimicrobial Activity of an Extract of Hermetia illucens Larvae Immunized with Lactobacillus casei against Salmonella Species.","authors":"Lee, Kyu-Shik; Yun, Eun-Young; Goo, Tae-Won","year":2020,"journal":"Insects, 11(10)","doi":"10.3390/insects11100704","pmid":"33076349","tags":["antimicrobial-peptides"],"studyType":"in vitro","evidenceStrength":"moderate","keyFinding":"L. casei-immunized black soldier fly larval extract produced cecropin and defensin peptides that inhibited Salmonella at 100-200 µg/100 µL with no cytotoxicity up to 40,000 µg/100 µL.","whyItMatters":"Salmonella contamination in food is a major public health issue. Insect-derived antimicrobial peptides could serve as natural food preservatives and antibiotic alternatives.","specificNumbers":"L. casei best inducer; cecropin 1 + defensin 1 upregulated; MICs 100-200 mcg/100 mcL; no cytotoxicity to 40,000 mcg; heat/pH stable","methodology":"In vitro study: larvae immunized with five Lactobacillus species; hemolymph collected and tested against three Salmonella species, S. aureus, and E. coli via MIC assays; gene expression analysis of AMPs; cytotoxicity tested on CaCo-2 and L929 cell lines.","limitations":"In vitro only — no animal infection models tested; extract composition not fully purified or characterized; shelf-life and commercial viability not assessed."},{"rthcId":"RPEP-04934","title":"Endocrine effects of the novel ghrelin receptor inverse agonist PF-5190457: Results from a placebo-controlled human laboratory alcohol co-administration study in heavy drinkers.","authors":"Lee, Mary R; Farokhnia, Mehdi; Cobbina, Enoch; Saravanakumar, Anitha; Li, Xiaobai; Battista, Jillian T; Farinelli, Lisa A; Akhlaghi, Fatemeh; Leggio, Lorenzo","year":2020,"journal":"Neuropharmacology, 170, 107788","doi":"10.1016/j.neuropharm.2019.107788","pmid":"31557492","tags":["growth-hormone-peptides","regulatory"],"studyType":"phase 1 clinical trial","evidenceStrength":"moderate","keyFinding":"PF-5190457 did not significantly alter blood levels of 13 hormones (including insulin, GLP-1, cortisol, thyroid hormones, and leptin) during dosing or alcohol co-administration.","whyItMatters":"For a drug targeting the ghrelin system (which intersects with appetite, growth hormone, and metabolism), showing minimal hormonal side effects is critical for clinical development.","specificNumbers":"13 hormones measured; largely unaffected during dosing and alcohol challenge; Phase 1b placebo-controlled","methodology":"Placebo-controlled Phase 1b human laboratory study in heavy drinkers. PF-5190457 dosed to steady state, then alcohol challenge administered. Blood drawn for 13 hormone panels at multiple timepoints.","limitations":"Small Phase 1b study (exact N not specified); short-term dosing only; endocrine safety over months/years of use unknown; efficacy for reducing drinking not reported here."},{"rthcId":"RPEP-04935","title":"Antigen processing and presentation in cancer immunotherapy.","authors":"Lee, Maxwell Y; Jeon, Jun W; Sievers, Cem; Allen, Clint T","year":2020,"journal":"Journal for immunotherapy of cancer, 8(2)","doi":"10.1136/jitc-2020-001111","pmid":"32859742","tags":["peptide-vaccines","cancer"],"studyType":"review","evidenceStrength":"n/a (review)","keyFinding":"Nearly one-third of experimentally validated T cell tumor antigens have MHC binding affinities (IC50 > 500 nM) below standard prediction cutoffs, highlighting the limitations of in silico approaches.","whyItMatters":"Personalized cancer vaccines depend on accurately predicting which tumor peptides the immune system will recognize. If algorithms miss one-third of real antigens, patients may receive suboptimal vaccines.","specificNumbers":"~33% of validated antigens had IC50 >500 nM; multi-step processing pathway; patient-specific validation recommended","methodology":"Literature review of antigen processing, presentation, epitope discovery, and computational prediction methods. Validated tumor antigens assessed against predicted MHC class I binding scores.","limitations":"Review article — no new experimental data generated; computational prediction tools have continued to improve since publication."},{"rthcId":"RPEP-04936","title":"Resolvin D3 controls mouse and human TRPV1-positive neurons and preclinical progression of psoriasis.","authors":"Lee, Sang Hoon; Tonello, Raquel; Im, Sang-Taek; Jeon, Hawon; Park, Jeongsu; Ford, Zachary; Davidson, Steve; Kim, Yong Ho; Park, Chul-Kyu; Berta, Temugin","year":2020,"journal":"Theranostics, 10(26), 12111-12126","doi":"10.7150/thno.52135","pmid":"33204332","tags":["neuropeptides","inflammation","pain-management"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"Resolvin D3 reversed psoriasiform itch and prevented skin inflammation by inhibiting TRPV1 and reducing CGRP in sensory neurons, with confirmed activity in human DRG neurons.","whyItMatters":"Current psoriasis biologics are expensive and have side effects. A naturally derived molecule that simultaneously addresses both itch and inflammation through neuronal pathways could offer a safer alternative.","specificNumbers":"2.8 mg/kg single dose reversed itch; repeated dosing prevented itch + inflammation; reduced CGRP; CGRP knockdown replicated effects; confirmed in human DRG neurons","methodology":"Mouse imiquimod psoriasis model with behavioral testing, DRG neuron electrophysiology, CGRP knockdown, and translational validation in human DRG neurons. RvD3 administered systemically at 2.8 mg/kg.","limitations":"Mouse model (imiquimod) doesn't perfectly replicate human psoriasis; human data limited to isolated neurons, not clinical psoriasis patients; long-term dosing effects unknown."},{"rthcId":"RPEP-04937","title":"Photoconjugation of an Fc-Specific Peptide Enables Efficient DAR 2 Antibody-Drug Conjugate Formation.","authors":"Lee, TaeJin; Kim, Ju Hwan; Kwon, Se Jeong; Park, Sun Hee; Kim, Jinyoung; Kang, Hyo Jin; Chung, Sang J","year":2020,"journal":"Organic letters, 22(21), 8419-8423","doi":"10.1021/acs.orglett.0c03049","pmid":"33074682","tags":["peptide-drug-development","cancer"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"A photoreactive Fc-binding peptide achieved site-specific conjugation to trastuzumab at Glu-382, enabling precise DAR 2 antibody-drug conjugate formation via click chemistry.","whyItMatters":"Current ADCs attach drugs randomly to antibodies, creating inconsistent products. Site-specific conjugation improves manufacturing reproducibility, drug-to-antibody ratio control, and potentially efficacy.","specificNumbers":"Site-specific at Glu-382; DAR 2; photoreactive Fc-binding peptide; click chemistry drug attachment","methodology":"Peptide chemistry and bioconjugation: designed high-affinity IgG Fc-binding peptide with photoreactive amino acid, UV-activated conjugation to trastuzumab, then click chemistry for drug attachment. Product characterized for DAR.","limitations":"Chemistry proof-of-concept only — no cell killing or in vivo efficacy data; only tested on trastuzumab; scalability of photoconjugation not assessed."},{"rthcId":"RPEP-04938","title":"Dual peptide-dendrimer conjugate inhibits acetylation of transforming growth factor β-induced protein and improves survival in sepsis.","authors":"Lee, Wonhwa; Park, Eun Ji; Kwon, Oh Kwang; Kim, Hyelim; Yoo, Youngbum; Kim, Shin-Woo; Seo, Young-Kyo; Kim, In-San; Na, Dong Hee; Bae, Jong-Sup","year":2020,"journal":"Biomaterials, 246, 120000","doi":"10.1016/j.biomaterials.2020.120000","pmid":"32247936","tags":["cell-penetrating-peptides","peptide-delivery","inflammation"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"PAMAM dendrimer nanoparticles decorated with both TAIP (anti-inflammatory peptide) and CPP (cell-penetrating peptide) improved mortality and organ damage in septic mice.","whyItMatters":"Sepsis kills over 250,000 Americans annually and has no approved targeted therapy. A nanoparticle approach that delivers anti-inflammatory peptides inside cells represents a potential breakthrough.","specificNumbers":"TAIP blocks TGFBIp acetylation at K676; CPP-PAMAM-PEG delivery; improved survival/organ damage; suppressed LPS-induced inflammation","methodology":"Peptide-dendrimer conjugation chemistry; in vitro endothelial cell inflammation assays with LPS; in vivo mouse sepsis survival model with organ damage assessment.","limitations":"Mouse sepsis model with unspecified group sizes; no comparison to standard of care; long-term toxicity of PAMAM dendrimers not assessed; human translation unclear."},{"rthcId":"RPEP-04939","title":"Primary culture of the rat spinal dorsal horn: a tool to investigate the effects of inflammatory stimulation on the afferent somatosensory system.","authors":"Leisengang, Stephan; Nürnberger, Franz; Ott, Daniela; Murgott, Jolanta; Gerstberger, Rüdiger; Rummel, Christoph; Roth, Joachim","year":2020,"journal":"Pflugers Archiv : European journal of physiology, 472(12), 1769-1782","doi":"10.1007/s00424-020-02478-y","pmid":"33098464","tags":["neuropeptides","pain-management","inflammation"],"studyType":"in vitro","evidenceStrength":"moderate","keyFinding":"Short-term inflammation reduces neuronal substance P responsiveness while long-term low-dose inflammation enhances glutamate sensitivity, with microglia driving the inflammatory cascade.","whyItMatters":"Understanding how inflammation reshapes pain signaling in the spinal cord is key to developing treatments for chronic inflammatory pain conditions.","specificNumbers":"43% neurons, 35% oligodendrocytes, 13% astrocytes, 9% microglia; 43% responded to substance P; 80% to glutamate; acute LPS reduced SP; chronic LPS enhanced glutamate","methodology":"Rat spinal dorsal horn primary cultures characterized by cell composition. Calcium imaging measured neuronal responses to substance P, glutamate, temperature, and PGE2. LPS used at two regimens: acute high-dose (10 µg/ml, 2h) and chronic low-dose (0.01 µg/ml, 24h). Cytokine and transcription factor expression measured.","limitations":"In vitro cell culture — lacks intact neural circuits and blood-brain barrier; rat tissue may not fully translate to human spinal cord; culture conditions may alter cell behavior."},{"rthcId":"RPEP-04940","title":"The effect of glucagon-like peptide-1 receptor agonists liraglutide and semaglutide on cardiovascular and renal outcomes across baseline blood pressure categories: Analysis of the LEADER and SUSTAIN 6 trials.","authors":"Leiter, Lawrence A; Bain, Stephen C; Bhatt, Deepak L; Buse, John B; Mazer, C David; Pratley, Richard E; Rasmussen, Søren; Ripa, Maria Sejersten; Vrazic, Hrvoje; Verma, Subodh","year":2020,"journal":"Diabetes, obesity & metabolism, 22(9), 1690-1695","doi":"10.1111/dom.14079","pmid":"32372454","tags":["semaglutide","glp-1-receptor-agonists","diabetes","cardiovascular"],"studyType":"post-hoc analysis of RCTs","evidenceStrength":"strong","keyFinding":"No statistical heterogeneity in cardiovascular (MACE) or nephropathy outcomes across blood pressure categories for either liraglutide or semaglutide vs placebo.","whyItMatters":"Clinicians can prescribe GLP-1 drugs for cardiovascular and kidney protection in type 2 diabetes without worrying that high or low blood pressure will negate the benefits.","specificNumbers":"LEADER: 9,340 patients; SUSTAIN 6: 3,297; 70-74% hypertensive; no heterogeneity for MACE or nephropathy across BP categories","methodology":"Post-hoc analysis of two randomized controlled trials (LEADER and SUSTAIN 6) using Cox proportional hazards models adjusted for cardiorenal risk factors, stratified by baseline BP category.","limitations":"Post-hoc analysis (not pre-specified); BP measured at baseline only (not longitudinally); separate trial analyses (not pooled); may lack power for some subgroups."},{"rthcId":"RPEP-04941","title":"Growth hormone-releasing hormone (GHRH) deficiency promotes inflammation-associated carcinogenesis.","authors":"Leone, Sheila; Chiavaroli, Annalisa; Recinella, Lucia; Di Valerio, Valentina; Veschi, Serena; Gasparo, Irene; Bitto, Alessandra; Ferrante, Claudio; Orlando, Giustino; Salvatori, Roberto; Brunetti, Luigi","year":2020,"journal":"Pharmacological research, 152, 104614","doi":"10.1016/j.phrs.2019.104614","pmid":"31874252","tags":["growth-hormone-peptides","cancer","inflammation"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"GHRH-deficient mice showed significantly increased tumor number, size, and invasiveness in a colon carcinogenesis model, with elevated COX-2, TNF-α, NF-κB, and iNOS.","whyItMatters":"This challenges the simplistic view that growth hormone signaling always promotes cancer. GHRH may actually protect against inflammation-driven cancers, which has implications for anti-aging interventions that suppress the somatotropic axis.","specificNumbers":"KO: more tumors, larger, distal colon, invasive adenocarcinomas; WT: adenomas only; KO higher PGE2, COX-2, TNF-α, NF-kB, iNOS","methodology":"GHRH knockout vs wild-type mice treated with AOM/DSS chemical carcinogenesis protocol. Endpoints: tumor count/size, histopathology, Disease Activity Index, inflammatory marker gene expression, PGE2 and 8-iso-PGF2α levels.","limitations":"Male mice only; cannot distinguish whether effects are from GHRH loss or secondary GH deficiency; group sizes not specified; chemical carcinogenesis model may not fully represent human colon cancer."},{"rthcId":"RPEP-04942","title":"Effective Therapeutic Drug Delivery by GALA3, an Endosomal Escape Peptide with Reduced Hydrophobicity.","authors":"Li, Chen; Cao, Xue-Wei; Zhao, Jian; Wang, Fu-Jun","year":2020,"journal":"The Journal of membrane biology, 253(2), 139-152","doi":"10.1007/s00232-020-00109-2","pmid":"32002589","tags":["cell-penetrating-peptides","peptide-delivery","cancer"],"studyType":"in vitro","evidenceStrength":"moderate","keyFinding":"GALA3 enhanced the cytotoxicity of BLF1-HBP fusion protein by at least 20-fold across H460, HeLa, A549, and SMCC-7721 cancer cell lines via pH-dependent endosomal escape.","whyItMatters":"Endosomal trapping is the biggest bottleneck for protein-based cancer drugs. A peptide that reliably breaks cargo out of endosomes could transform biologics delivery.","specificNumbers":"GALA3 > HA2; ≥20x cytotoxicity improvement; pH-dependent escape; 4 cell lines tested","methodology":"In vitro study: synthetic GALA variants with varying hydrophobicity tested for endosomal escape efficiency; GALA3-BLF1-HBP fusion protein tested for cytotoxicity in 4 cancer cell lines; compared to HA2 and other escape peptides; pH-dependent mechanism confirmed.","limitations":"In vitro only — no animal tumor models; fused to a specific protein (BLF1-HBP), generalizability to other cargoes unknown; no toxicity or biodistribution data."},{"rthcId":"RPEP-04943","title":"The Role of Substance P in the Regulation of Bone and Cartilage Metabolic Activity.","authors":"Li, Fu-Xing-Zi; Xu, Feng; Lin, Xiao; Wu, Feng; Zhong, Jia-Yu; Wang, Yi; Guo, Bei; Zheng, Ming-Hui; Shan, Su-Kang; Yuan, Ling-Qing","year":2020,"journal":"Frontiers in endocrinology, 11, 77","doi":"10.3389/fendo.2020.00077","pmid":"32180759","tags":["neuropeptides","bone-health"],"studyType":"review","evidenceStrength":"n/a (review)","keyFinding":"Substance P regulates bone and cartilage metabolism through autocrine/paracrine signaling, promoting cell proliferation, differentiation, matrix synthesis, and fracture healing.","whyItMatters":"Understanding how nerves communicate with bones and cartilage through substance P could lead to new treatments for osteoporosis, arthritis, and poor fracture healing.","specificNumbers":"SP regulates proliferation, differentiation, apoptosis, matrix synthesis/degradation; autocrine/paracrine in bone and cartilage cells","methodology":"Narrative literature review synthesizing recent research on substance P in bone metabolism, cartilage biology, and fracture healing.","limitations":"Narrative review — no systematic methodology; mostly based on pre-clinical studies; clinical translation of SP-based therapies remains uncertain."},{"rthcId":"RPEP-04944","title":"The protective effects of dulaglutide against advanced glycation end products (AGEs)-induced degradation of type Ⅱ collagen and aggrecan in human SW1353 chondrocytes.","authors":"Li, Hai; Chen, Jianhai; Li, Biao; Fang, Xiaoyan","year":2020,"journal":"Chemico-biological interactions, 322, 108968","doi":"10.1016/j.cbi.2020.108968","pmid":"32004530","tags":["glp-1-receptor-agonists","bone-health","inflammation","diabetes"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Dulaglutide protected chondrocytes from AGE-induced cartilage matrix degradation by reducing MMP-3/13, ADAMTS-4/5, inflammatory cytokines, and ROS via NF-κB pathway inhibition.","whyItMatters":"Millions of people with diabetes also have osteoarthritis. If GLP-1 drugs already being taken for diabetes also protect joints, this could be a major secondary benefit.","specificNumbers":"Preserved collagen II and aggrecan; reduced MMP-3, MMP-13, ADAMTS-4, ADAMTS-5; inhibited cytokines, chemokines, ROS; NF-kB pathway","methodology":"In vitro study using human SW1353 chondrocyte cell line. Cells exposed to AGEs with/without dulaglutide. Measured: type II collagen, aggrecan, MMP-3/13, ADAMTS-4/5, inflammatory cytokines, ROS, COX-2/PGE2, NF-κB activation, and GLP-1R expression.","limitations":"Single cell line (SW1353) — not primary human chondrocytes; in vitro only; AGE concentrations may not reflect in vivo levels; no animal or clinical data."},{"rthcId":"RPEP-04945","title":"An efficient controlled release strategy for hypertension therapy: Folate-mediated lipid nanoparticles for oral peptide delivery.","authors":"Li, Jinhua; Chen, Bin; Yu, Ting; Guo, Mengran; Zhao, Shengnan; Zhang, Yi; Jin, Chaohui; Peng, Xingchen; Zeng, Jun; Yang, Jian; Song, Xiangrong","year":2020,"journal":"Pharmacological research, 157, 104796","doi":"10.1016/j.phrs.2020.104796","pmid":"32278048","tags":["peptide-delivery","cardiovascular","bioactive-peptides"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"FA-VP5-LNPs achieved 30.71-fold higher oral bioavailability (AUC0-72h) than free VP5 peptide and sustained antihypertensive effects for 6 days.","whyItMatters":"Oral peptide delivery is a major pharmaceutical challenge. A 30-fold bioavailability improvement with sustained 6-day activity could transform how peptide drugs are administered.","specificNumbers":"30.71x bioavailability improvement; 6-day antihypertensive effect; folate-PLGA-lipid nanoparticles; no toxicity","methodology":"Nanoparticle formulation (PLGA core + folate-lipid shell), in vitro release studies, Caco-2/HT29 cell uptake, in situ rat intestinal absorption, in vivo pharmacokinetics, and blood pressure monitoring in rat hypertension model.","limitations":"Rat study with unspecified group sizes; folate receptor expression varies between species; long-term safety and manufacturing scalability not assessed; only one peptide tested."},{"rthcId":"RPEP-04946","title":"Profiling of inflammatory mediators in the synovial fluid related to pain in knee osteoarthritis.","authors":"Li, Li; Li, Zhenxing; Li, Yuyan; Hu, Xi; Zhang, Yu; Fan, Pei","year":2020,"journal":"BMC musculoskeletal disorders, 21(1), 99","doi":"10.1186/s12891-020-3120-0","pmid":"32059658","tags":["neuropeptides","pain-management","bone-health","inflammation"],"studyType":"human observational","evidenceStrength":"moderate","keyFinding":"IL-1β, IL-6, and TNF-α in synovial fluid correlated with pain in early knee OA, but CGRP, substance P, neuropeptide Y, and matrix enzymes (MMP-3/13) did not correlate with pain scores.","whyItMatters":"Understanding which inflammatory mediators drive knee pain at different disease stages is essential for developing targeted pain treatments beyond generic anti-inflammatories.","specificNumbers":"86 patients; IL-1β/IL-6 higher early stage; NRS negative with TNF-α; VAS negative with IL-1β, IL-6, TNF-α; no neuropeptide-pain correlations","methodology":"Cross-sectional human observational study: synovial fluid from 86 KOA patients analyzed by ELISA for 11 mediators; pain assessed via NRS, VAS, WOMAC, and PainDETECT; radiological grading by Kellgren-Lawrence scale.","limitations":"Cross-sectional design (no longitudinal tracking); 86 patients limits subgroup power; synovial fluid sampling variability; neuropeptide levels may be affected by collection technique."},{"rthcId":"RPEP-04947","title":"Delivery of myo-Inositol Hexakisphosphate to the Cell Nucleus with a Proline-Based Cell-Penetrating Peptide.","authors":"Li, Mao; Puschmann, Robert; Herdlitschka, Andreas; Fiedler, Dorothea; Wennemers, Helma","year":2020,"journal":"Angewandte Chemie (International ed. in English), 59(36), 15586-15589","doi":"10.1002/anie.202006770","pmid":"32558101","tags":["cell-penetrating-peptides","peptide-delivery"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Cationic oligoproline Z8 binds InsP6 with high affinity, undergoes a PPII-helix-to-aggregate conformational change, and delivers InsP6 to the nucleus more effectively than octaarginine.","whyItMatters":"Delivering specific molecules to the cell nucleus is essential for studying signaling pathways and developing gene therapies. Proline-based peptides offer a new structural class of nuclear delivery vehicles.","specificNumbers":"Z8 octa-guanidiniumproline; PPII-helix to aggregate upon binding; considerably > octaarginine for nuclear InsP6 delivery","methodology":"Biophysical characterization (CD spectroscopy, binding affinity, dynamic light scattering), computational modeling of Z8-InsP6 interaction, and cell culture delivery experiments comparing Z8 to octaarginine.","limitations":"In vitro only; only one cargo molecule tested (InsP6); nuclear specificity mechanism not fully elucidated; no in vivo data."},{"rthcId":"RPEP-04948","title":"A novel mitochondrial targeted hybrid peptide modified HPMA copolymers for breast cancer metastasis suppression.","authors":"Li, Qiuyi; Yang, Jiatao; Chen, Cheng; Lin, Xi; Zhou, Minglu; Zhou, Zhou; Huang, Yuan","year":2020,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 325, 38-51","doi":"10.1016/j.jconrel.2020.06.010","pmid":"32598957","tags":["cell-penetrating-peptides","peptide-delivery","cancer"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"P-D-R8MTS completely prevented lung metastasis in 4T1-bearing mice while inhibiting tumor growth, by delivering doxorubicin to mitochondria and downregulating MMP-2, VEGF, and TGF-β.","whyItMatters":"Metastasis — not the primary tumor — kills most cancer patients. A delivery system that specifically targets cancer cell mitochondria to block both tumor growth and spread addresses the most lethal aspect of breast cancer.","specificNumbers":"R8+ALD5MTS hybrid peptide; HPMA-DOX carrier; pH-responsive release; no lung metastasis; downregulated MMP-2, VEGF, TGF-β","methodology":"Polymer-peptide-drug conjugate design; in vitro testing on 4T1 and MDA-MB-231 breast cancer cells (proliferation, migration, invasion assays); in vivo 4T1 mouse tumor model with lung metastasis assessment; protein analysis of MMP-2, VEGF, TGF-β.","limitations":"Mouse model with unspecified group sizes; only breast cancer tested; long-term toxicity of the polymer-peptide system not fully characterized; doxorubicin cardiotoxicity concerns remain."},{"rthcId":"RPEP-04949","title":"Hydrocarbon staple constructing highly efficient α-helix cell-penetrating peptides for intracellular cargo delivery.","authors":"Li, Shu; Zhang, Xingjiao; Guo, Chen; Peng, Yali; Liu, Xiaojing; Wang, Bo; Zhuang, Ran; Chang, Min; Wang, Rui","year":2020,"journal":"Chemical communications (Cambridge, England), 56(100), 15655-15658","doi":"10.1039/d0cc06312f","pmid":"33355559","tags":["cell-penetrating-peptides","cyclic-peptides","peptide-delivery"],"studyType":"in vitro","evidenceStrength":"moderate","keyFinding":"Hydrocarbon-stapled Tat peptides showed correlated improvements in helicity, hydrophobicity, heparan sulfate binding, cellular uptake, endosomal escape, and proteolytic stability with low cytotoxicity.","whyItMatters":"Cell-penetrating peptides are limited by poor stability and endosomal trapping. Stapling addresses both problems simultaneously, making CPPs more practical for drug delivery.","specificNumbers":"Hydrophobicity/helicity correlated with uptake; higher heparan sulfate affinity; increased endosomal escape; high proteolytic stability; low cytotoxicity","methodology":"Systematic peptide design with hydrocarbon staples at various positions; cellular uptake quantification; heparan sulfate binding assays; endosomal escape analysis; protease stability testing; cytotoxicity assessment.","limitations":"In vitro only; cargo delivery efficiency not quantified for specific therapeutics; manufacturing cost of stapled peptides is higher; in vivo performance unknown."},{"rthcId":"RPEP-04950","title":"Stapled Helical Peptides Bearing Different Anchoring Residues.","authors":"Li, Xiang; Chen, Si; Zhang, Wei-Dong; Hu, Hong-Gang","year":2020,"journal":"Chemical reviews, 120(18), 10079-10144","doi":"10.1021/acs.chemrev.0c00532","pmid":"32794722","tags":["cyclic-peptides","peptide-drug-development"],"studyType":"review","evidenceStrength":"n/a (review)","keyFinding":"Stapled peptide design should consider anchoring residue type, cross-linker chemistry, staple length, and staple position — each significantly affects helicity, stability, cell permeability, and target binding.","whyItMatters":"Protein-protein interactions drive most diseases but are \"undruggable\" by small molecules. Stapled peptides are the leading approach to crack this target class, and this review provides a practical design guide.","specificNumbers":"3 anchoring residue categories; covers stability, permeability, PPI inhibition; reversibility, bio-orthogonal, photoisomerization features","methodology":"Comprehensive literature review categorizing peptide stapling methodologies by anchoring residue chemistry, with analysis of biophysical and biological properties.","limitations":"Review — no new experimental data; the field evolves rapidly with new stapling chemistries being developed continuously."},{"rthcId":"RPEP-04951","title":"Neurotrophic and neuroprotective effects of a monomeric GLP-1/GIP/Gcg receptor triagonist in cellular and rodent models of mild traumatic brain injury.","authors":"Li, Yazhou; Glotfelty, Elliot J; Namdar, Inbar; Tweedie, David; Olson, Lars; Hoffer, Barry J; DiMarchi, Richard D; Pick, Chagi G; Greig, Nigel H","year":2020,"journal":"Experimental neurology, 324, 113113","doi":"10.1016/j.expneurol.2019.113113","pmid":"31730763","tags":["glp-1-receptor-agonists","neurological-conditions"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"Triagonist (GLP-1/GIP/Gcg agonist) fully mitigated mTBI-induced visual and spatial memory deficits at 7 and 30 days post-injury via balanced activation of all three receptors.","whyItMatters":"Mild TBI (concussion) affects millions yearly with no approved treatment. A peptide drug originally designed for metabolic disease that also protects the brain could be rapidly repurposed.","specificNumbers":"Triple agonist (GLP-1/GIP/Gcg); 7-day SC treatment; fully reversed visual/spatial memory deficits at d7 and d30; protected vs oxidative stress and glutamate toxicity","methodology":"In vitro: SH-SY5Y neuronal cells treated with Triagonist; cAMP, oxidative stress, and glutamate toxicity assays; receptor antagonist blockade experiments. In vivo: mouse 30g weight-drop mTBI model; 7 days daily subcutaneous Triagonist; memory testing at 7 and 30 days post-injury.","limitations":"Mouse model with unspecified group sizes; mild TBI only (not moderate/severe); mechanism of neuroprotection not fully elucidated in vivo; clinically translatable dose claim not validated in humans."},{"rthcId":"RPEP-04952","title":"The in vitro bioavailability of anti-platelet peptides in collagen hydrolysate from silver carp (Hypophthalmichthys molitrix) skin.","authors":"Li, Yuqi; Wang, Bo; Li, Bo","year":2020,"journal":"Journal of food biochemistry, 44(6), e13226","doi":"10.1111/jfbc.13226","pmid":"32266991","tags":["collagen-peptides","cardiovascular","bioactive-peptides"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Peptides GPR, GPRG, and GPRGP from fish collagen resisted GI digestion, were absorbed by Caco-2 cells, and inhibited platelet aggregation (IC50: 0.160-0.917 mg/ml) without bleeding risk.","whyItMatters":"Blood clots cause heart attacks and strokes. A dietary supplement from fish skin collagen that prevents clotting without bleeding risk could be a safe preventive option for at-risk populations.","specificNumbers":"GPR/GPRG/GPRGP; ADP IC50 0.160-0.283 mg/mL; thrombin IC50 0.714-1.008 mg/mL; survived GI digestion; Caco-2 absorbed; no mouse bleeding","methodology":"Simulated gastrointestinal digestion stability; Caco-2 intestinal absorption model; ADP- and thrombin-induced platelet aggregation assays; platelet thrombus formation time; coagulation cascade analysis; mouse bleeding safety test.","limitations":"In vitro bioavailability model (not in vivo absorption); IC50 values relatively high for oral dosing; mouse bleeding test not a comprehensive safety study; no human data."},{"rthcId":"RPEP-04953","title":"Dietary vitamin A deficiency reduces growth performance, immune function of intestine, and alters tight junction proteins of intestine for juvenile hybrid grouper (Epinephelus fuscoguttatus ♀ × Epinephelus lanceolatus ♂).","authors":"Liang, Dazhi; Yang, Qihui; Tan, Beiping; Dong, Xiaohui; Chi, Shuyan; Liu, Hongyu; Zhang, Shuang","year":2020,"journal":"Fish & shellfish immunology, 107(Pt A), 346-356","doi":"10.1016/j.fsi.2020.10.016","pmid":"33068761","tags":["antimicrobial-peptides","gut-health"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"Vitamin A deficiency downregulated intestinal antimicrobial peptides (β-defensin, hepcidin, epinecidin) and tight junction proteins while upregulating pro-inflammatory cytokines in grouper.","whyItMatters":"This demonstrates that vitamin A is essential for maintaining intestinal antimicrobial peptide production and gut barrier integrity — a principle that likely applies across vertebrates including humans.","specificNumbers":"Optimal VA: 2,689-4,096 IU/kg; reduced β-defensin, hepcidin, epinecidin; reduced IL-10, TGF-β1, occludin, claudin3; increased TNF-α, IL-1β, NF-κB","methodology":"Dose-response feeding trial: 6 VA levels (317-15,204 IU/kg), triplicate groups, 7-week duration. Measured: growth, serum/intestinal enzymes, gut morphology, AMP gene expression, cytokine expression, tight junction protein mRNA.","limitations":"Fish model — results may not directly translate to mammalian intestinal biology; gene expression measured by mRNA only (not protein levels); specific grouper species may have unique nutritional requirements."},{"rthcId":"RPEP-04954","title":"Signaling mechanisms of growth hormone-releasing hormone receptor in LPS-induced acute ocular inflammation.","authors":"Liang, Wei Cheng; Ren, Jia Lin; Yu, Qiu Xiao; Li, Jian; Ng, Tsz Kin; Chu, Wai Kit; Qin, Yong Jie; Chu, Kai On; Schally, Andrew V; Pang, Chi Pui; Chan, Sun On","year":2020,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 117(11), 6067-6074","doi":"10.1073/pnas.1904532117","pmid":"32123064","tags":["growth-hormone-peptides","inflammation"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"GHRH-R specifically activates JAK2/STAT3 signaling in ocular inflammation; both the GHRH-R antagonist MIA-602 and JAK inhibitor ruxolitinib reduced acute uveitis.","whyItMatters":"Uveitis is a leading cause of blindness with limited treatment options. Identifying GHRH-R as a druggable inflammatory mediator in the eye opens new therapeutic avenues.","specificNumbers":"GHRH-R → JAK2 → STAT3 → IL-6/IL-17A/COX2/iNOS; MIA-602 suppressed STAT3; ruxolitinib partially alleviated uveitis in vivo","methodology":"Multi-model approach: human ciliary epithelial cells, rat iris/ciliary body explants, and in vivo rat endotoxin-induced uveitis. Methods included co-immunoprecipitation, bioinformatics, phosphorylation assays, and inflammatory marker quantification.","limitations":"Rat model of endotoxin-induced uveitis may not fully represent autoimmune uveitis in humans; ruxolitinib only partially alleviated inflammation; MIA-602 not tested in vivo in this study."},{"rthcId":"RPEP-04955","title":"The Dual Role of Antimicrobial Peptides in Autoimmunity.","authors":"Liang, Wenjie; Diana, Julien","year":2020,"journal":"Frontiers in immunology, 11, 2077","doi":"10.3389/fimmu.2020.02077","pmid":"32983158","tags":["antimicrobial-peptides","immune-function","inflammation"],"studyType":"review","evidenceStrength":"n/a (review)","keyFinding":"AMPs demonstrate context-dependent dual roles in autoimmunity — pro-inflammatory in some diseases (driving autoimmune pathology) and anti-inflammatory in others (providing protection).","whyItMatters":"Autoimmune diseases affect ~8% of the population. Understanding whether AMPs help or hurt in specific conditions is critical before they can be safely used as therapies.","specificNumbers":"LL-37 as autoantigen in psoriasis/lupus; defensins with anti-inflammatory roles; dual nature across disease contexts","methodology":"Narrative literature review synthesizing evidence on AMP roles across multiple autoimmune diseases, examining both innate and adaptive immune mechanisms.","limitations":"Narrative review — no systematic methodology; much of the evidence comes from animal models; the mechanisms governing which role AMPs play remain poorly understood."},{"rthcId":"RPEP-04956","title":"Three Newly Isolated Calcium-Chelating Peptides from Tilapia Bone Collagen Hydrolysate Enhance Calcium Absorption Activity in Intestinal Caco-2 Cells.","authors":"Liao, Wanwen; Chen, Hui; Jin, Wengang; Yang, Zhennai; Cao, Yong; Miao, Jianyin","year":2020,"journal":"Journal of agricultural and food chemistry, 68(7), 2091-2098","doi":"10.1021/acs.jafc.9b07602","pmid":"31927882","tags":["collagen-peptides","bone-health","bioactive-peptides"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"FDHIVY peptide from tilapia bone collagen enhanced intestinal calcium transport by 202% in Caco-2 cells within 30 minutes via calcium chelation.","whyItMatters":"Calcium deficiency affects billions worldwide. Peptides that enhance calcium absorption from food could improve bone health without requiring high-dose calcium supplements.","specificNumbers":"GPAGPHGPVG 89%, FDHIVY 202%, YQEPVIAPKL 130% calcium transport enhancement; Ca-chelating: 18.80, 35.73, 28.4 mg/g","methodology":"Peptide isolation by RP-HPLC from tilapia bone collagen hydrolysate; sequence determination by LC-MS/MS; synthetic peptide calcium-chelating assays; Caco-2 cell monolayer calcium transport assays.","limitations":"In vitro Caco-2 model only — may not reflect in vivo absorption; peptide stability during digestion not tested; effective oral dose for humans unknown."},{"rthcId":"RPEP-04957","title":"Effects of inhalation of sevoflurane at different concentrations on TRPV1 in airways of rats at different developmental stages.","authors":"Liu, Dexing; Yuan, Jie; Fei, Xia; Zhu, Yuhang; Zhou, Yannan; Zhang, Chao; Dong, Liang; Zhu, Zhaoqiong","year":2020,"journal":"Life sciences, 249, 117472","doi":"10.1016/j.lfs.2020.117472","pmid":"32112870","tags":["neuropeptides","pain-management"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"Low-dose sevoflurane upregulated TRPV1 and airway neuropeptides (CGRP, SP, NKA, NKB) in developing rats but not in mature rats, with effects blocked by TRPV1 antagonist capsazepine.","whyItMatters":"Sevoflurane is the most common anesthetic for children. Understanding why young airways react differently helps anesthesiologists manage pediatric airway complications like bronchospasm and laryngospasm.","specificNumbers":"1.5% sevoflurane increased TRPV1/CGRP/SP/NKA/NKB in young rats; blocked by capsazepine; not seen in 42-day-old rats; 2.6% decreased NKA/NKB in older rats","methodology":"Rat inhalation study across 3 age groups (14, 21, 42 days) with 2 sevoflurane concentrations (1.5%, 2.6%) + controls. TRPV1 by Western blot; neuropeptides by immunohistochemistry; capsazepine pretreatment for mechanism confirmation.","limitations":"Rat airway physiology may differ from human; specific group sizes not detailed; only two concentrations tested; no functional airway measurements (resistance, compliance)."},{"rthcId":"RPEP-04958","title":"In Vitro Assays: Friends or Foes of Cell-Penetrating Peptides.","authors":"Liu, Jinsha; Afshar, Sepideh","year":2020,"journal":"International journal of molecular sciences, 21(13)","doi":"10.3390/ijms21134719","pmid":"32630650","tags":["cell-penetrating-peptides","peptide-drug-development"],"studyType":"review","evidenceStrength":"n/a (review)","keyFinding":"CPP uptake efficiency is highly dependent on experimental methodology; a single assay can be misleading, and orthogonal assay approaches are necessary for reliable evaluation.","whyItMatters":"If CPP researchers pick the wrong assay, they may advance peptides that don't actually work in real biological contexts — wasting time and resources in drug development.","specificNumbers":"Multiple assay types cataloged; CPP performance varies with concentration, membrane, cargo, methodology; orthogonal assays recommended","methodology":"Comprehensive literature review of in vitro assay methods for CPP evaluation, including fluorescence-based assays, flow cytometry, confocal microscopy, and functional cargo delivery readouts.","limitations":"Review — no new experimental data; the authors provide recommendations but don't validate a specific optimal assay protocol."},{"rthcId":"RPEP-04959","title":"Sensory neurons directly promote angiogenesis in response to inflammation via substance P signaling.","authors":"Liu, Lingjia; Dana, Reza; Yin, Jia","year":2020,"journal":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 34(5), 6229-6243","doi":"10.1096/fj.201903236R","pmid":"32162744","tags":["neuropeptides","eye-health","wound-healing","inflammation"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"Sensory neurons from dry eye mice promoted vascular endothelial cell proliferation and tube formation via substance P signaling; blocking SP with spantide I prevented corneal neovascularization.","whyItMatters":"Corneal neovascularization threatens vision in millions with dry eye disease. Targeting substance P could provide a new approach to prevent abnormal blood vessel invasion of the cornea.","specificNumbers":"DED neurons secreted higher SP levels; spantide I significantly reduced corneal neovascularization","methodology":"Mouse dry eye model (desiccating stress); trigeminal ganglion neuron/VEC co-culture system; SP secretion measurement; spantide I (NK-1 antagonist) treatment in vivo and in vitro; siRNA knockdown of SP.","limitations":"Mouse model of dry eye; co-culture system is simplified compared to in vivo tissue; substance P may not be the only neuropeptide involved; human validation needed."},{"rthcId":"RPEP-04960","title":"Inhibition of the ATP synthase sensitizes Staphylococcus aureus towards human antimicrobial peptides.","authors":"Liu, Liping; Beck, Christian; Nøhr-Meldgaard, Katrine; Peschel, Andreas; Kretschmer, Dorothee; Ingmer, Hanne; Vestergaard, Martin","year":2020,"journal":"Scientific reports, 10(1), 11391","doi":"10.1038/s41598-020-68146-4","pmid":"32647350","tags":["antimicrobial-peptides","ll-37","infection"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"ATP synthase inactivation sensitized S. aureus to killing by hBD2, hBD4, LL-37, and histatin 5; resveratrol (an ATP synthase inhibitor) reproduced this sensitization.","whyItMatters":"Instead of developing new antibiotics, this approach would make S. aureus infections treatable by the body's own immune peptides — a strategy resistant bacteria would find harder to counter.","specificNumbers":"Increased susceptibility to 4/6 AMPs; resveratrol sensitized WT to hBD4; atpA mutant more susceptible to neutrophil killing","methodology":"In vitro: S. aureus wild-type vs ATP synthase mutant (atpA) tested against six human AMPs (hBD1-4, LL-37, histatin 5); resveratrol treatment; neutrophil killing assays with and without oxidative burst inhibition.","limitations":"In vitro only; resveratrol concentrations needed may not be achievable in vivo; ATP synthase inhibition could affect host cells; mechanism of selectivity for some AMPs but not others unclear."},{"rthcId":"RPEP-04961","title":"The Ras/ERK signaling pathway couples antimicrobial peptides to mediate resistance to dengue virus in Aedes mosquitoes.","authors":"Liu, Wen-Quan; Chen, Si-Qi; Bai, Hao-Qiang; Wei, Qi-Mei; Zhang, Sheng-Nan; Chen, Chen; Zhu, Yi-Han; Yi, Tang-Wei; Guo, Xiao-Pu; Chen, Si-Yuan; Yin, Meng-Jie; Sun, Chen-Feng; Liang, Shao-Hui","year":2020,"journal":"PLoS neglected tropical diseases, 14(8), e0008660","doi":"10.1371/journal.pntd.0008660","pmid":"32866199","tags":["antimicrobial-peptides","infection","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Ras/ERK signaling activates defensin C in Aedes mosquitoes to restrict DENV infection; ERK knockdown (but not JNK or p38) significantly enhanced viral replication.","whyItMatters":"Understanding how mosquitoes naturally fight dengue could lead to strategies for engineering mosquitoes with enhanced viral resistance, reducing dengue transmission to humans.","specificNumbers":"ERK knockdown enhanced DENV replication; Ras/ERK activation decreased viral titers; defensin C restricts DENV","methodology":"Mosquito cell and midgut studies using RNA interference knockdown (ERK, JNK, p38), pharmacological activation/inhibition of Ras/ERK, viral titer measurement, and AMP expression analysis.","limitations":"Mosquito cell and midgut studies — not whole-organism transmission experiments; defensin C may not be the only AMP involved; applicability to other mosquito-borne viruses unknown."},{"rthcId":"RPEP-04962","title":"Lactobacillus plantarum PS128 Ameliorated Visceral Hypersensitivity in Rats Through the Gut-Brain Axis.","authors":"Liu, Yen-Wenn; Wang, Yen-Po; Yen, Hsu-Fang; Liu, Pei-Yi; Tzeng, Wen-Jian; Tsai, Chia-Fen; Lin, Han-Chieh; Lee, Fa-Yauh; Jeng, One-Jang; Lu, Ching-Liang; Tsai, Ying-Chieh","year":2020,"journal":"Probiotics and antimicrobial proteins, 12(3), 980-993","doi":"10.1007/s12602-019-09595-w","pmid":"31691208","tags":["neuropeptides","gut-healing","pain","inflammation"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"PS128 reversed 5-HTP-induced visceral hypersensitivity and normalized substance P, CGRP, BDNF, and NGF distribution between dorsal root ganglia and spinal cord.","whyItMatters":"IBS affects 10-15% of people globally with limited treatment options. A probiotic that modulates the gut-brain axis through neuropeptide pathways offers a mechanistically grounded approach.","specificNumbers":"10^9 CFU/day x 14 days; reversed SP, CGRP, BDNF, NGF changes; lowered corticosterone","methodology":"Rat IBS model (5-HTP-induced visceral hypersensitivity without inflammation); 14 days oral PS128 (10⁹ CFU/day); colorectal distension with EMG; neuropeptide and neurotrophin levels in DRG, spinal cord; serum corticosterone; amygdala receptor expression.","limitations":"Rat model — IBS in humans is more complex; 5-HTP model mimics only one aspect of IBS; 14 days may not reflect long-term effects; single probiotic strain tested."},{"rthcId":"RPEP-04963","title":"Thymosin Alpha 1 Reduces the Mortality of Severe Coronavirus Disease 2019 by Restoration of Lymphocytopenia and Reversion of Exhausted T Cells.","authors":"Liu, Yueping; Pan, Yue; Hu, Zhenhong; Wu, Ming; Wang, Chenhui; Feng, Zeqing; Mao, Congzheng; Tan, Yingjun; Liu, Ying; Chen, Li; Li, Min; Wang, Gang; Yuan, Zilin; Diao, Bo; Wu, Yuzhang; Chen, Yongwen","year":2020,"journal":"Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 71(16), 2150-2157","doi":"10.1093/cid/ciaa630","pmid":"32442287","tags":["thymosin-alpha-1","immune-function","infection","clinical-trials"],"studyType":"retrospective","evidenceStrength":"moderate-high","keyFinding":"Tα1 reduced severe COVID-19 mortality from 30% to 11.1% (P=.044), restored CD4+ and CD8+ T cell counts, and reversed T cell exhaustion markers (PD-1, Tim-3).","whyItMatters":"Severe COVID-19 kills partly through immune exhaustion. A peptide that restores T cell function rather than suppressing immunity addresses the root cause — and may apply to other viral infections.","specificNumbers":"Mortality 11.11% vs 30.00% (p=0.044); benefit threshold CD8+ <400/uL or CD4+ <650/uL; reduced PD-1 and Tim-3 on CD8+ T cells","methodology":"Retrospective review of 76 severe COVID-19 patients from 2 Wuhan hospitals (Dec 2019-Mar 2020). Tα1-treated vs untreated; measured: mortality, T cell counts, TRECs (thymic output), PD-1 and Tim-3 expression on CD8+ T cells by flow cytometry.","limitations":"Retrospective non-randomized study — potential selection bias; small sample (76); single-center data from early pandemic (Dec 2019-Mar 2020); no standardized treatment protocol."},{"rthcId":"RPEP-04964","title":"Induction of diabetes in cynomolgus monkey with one shot of analytical grade streptozotocin.","authors":"Liu, Zhengzhao; Lu, Ying; Hu, Wenbao; Hara, Hidetaka; Dai, Yifan; Cai, Zhiming; Mou, Lisha","year":2020,"journal":"Animal models and experimental medicine, 3(1), 79-86","doi":"10.1002/ame2.12109","pmid":"32318663","tags":["diabetes","research-status"],"studyType":"animal","evidenceStrength":"low","keyFinding":"Single 100 mg/kg dose of analytical-grade STZ induced complete diabetes in cynomolgus monkeys with destroyed beta cells and <0.5 ng/mL stimulated C-peptide, without organ toxicity.","whyItMatters":"Primate diabetes models are essential for testing islet transplants and peptide-based diabetes drugs. This accessible method removes the barrier of needing expensive clinical-grade STZ.","specificNumbers":"100 mg/kg STZ IV; C-peptide <0.5 ng/mL; triphasic blood glucose response; no vomiting or organ toxicity","methodology":"3 cynomolgus monkeys received IV STZ (100 mg/kg over 5 min). Blood glucose monitored hourly for 48h then twice daily. C-peptide by ELISA; liver/renal function blood chemistry; islet immunohistochemistry for insulin and glucagon.","limitations":"Only 3 animals — very small sample; no long-term follow-up reported; single STZ source tested; model represents type 1 (beta cell destruction), not type 2 diabetes."},{"rthcId":"RPEP-04965","title":"PEG-coated nanoparticles detachable in acidic microenvironments for the tumor-directed delivery of chemo- and gene therapies for head and neck cancer.","authors":"Lo, Yu-Li; Chang, Chih-Hsien; Wang, Chen-Shen; Yang, Muh-Hwa; Lin, Anya Maan-Yuh; Hong, Ci-Jheng; Tseng, Wei-Hsuan","year":2020,"journal":"Theranostics, 10(15), 6695-6714","doi":"10.7150/thno.45164","pmid":"32550898","tags":["cell-penetrating","cancer","peptide-delivery"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"Triple-peptide pH-responsive nanoparticles co-delivering irinotecan and miR-200 outperformed Onivyde in a head and neck cancer mouse model by simultaneously targeting EMT, MDR, and Wnt pathways.","whyItMatters":"Head and neck cancers resist treatment through EMT and drug resistance pathways. Combining chemo with gene therapy in a single smart nanoparticle attacks both problems simultaneously.","specificNumbers":"Outperformed Onivyde; regulated Wnt/beta-catenin, MDR, EMT pathways; 3 peptide types used for targeting","methodology":"Nanoparticle design with pH-cleavable PEG + 3 peptides; physicochemical characterization; SAS cell cytotoxicity and uptake; pathway analysis (Wnt, MDR, EMT); in vivo SAS tumor-bearing mouse efficacy and safety studies; compared to Onivyde.","limitations":"Mouse tumor model with single cancer type (tongue SCC); complex multi-component formulation may be hard to manufacture at scale; long-term toxicity not assessed."},{"rthcId":"RPEP-04966","title":"Evaluation of serum level of substance P and tissue distribution of NK-1 receptor in colorectal cancer.","authors":"Lorestani, Shima; Ghahremanloo, Atefeh; Jangjoo, Ali; Abedi, Maedeh; Hashemy, Seyed Isaac","year":2020,"journal":"Molecular biology reports, 47(5), 3469-3474","doi":"10.1007/s11033-020-05432-4","pmid":"32277443","tags":["neuropeptides","cancer"],"studyType":"observational","evidenceStrength":"low-moderate","keyFinding":"Serum substance P was significantly elevated in CRC patients (P=0.001) and tumor tissues overexpressed NK-1R compared to adjacent normal tissue (P=0.01).","whyItMatters":"NK-1 receptor antagonists (like aprepitant, used for nausea) already exist. If SP/NK-1R drives colorectal cancer, these drugs could potentially be repurposed as cancer therapies.","specificNumbers":"SP elevated in serum (p=0.001); NK-1R higher in tumor vs adjacent tissue (p=0.01); no correlation with tumor size or lymph nodes","methodology":"Observational study: 38 CRC patients; serum substance P by ELISA (cases vs healthy controls); NK-1R immunohistochemistry in tumor vs adjacent normal tissue; correlation with tumor size and lymph node status.","limitations":"Small sample (38 patients); no correlation with clinical outcomes (survival); observational design — cannot prove causation; NK-1R expression didn't correlate with tumor characteristics."},{"rthcId":"RPEP-04967","title":"A mouse model for vitamin D-induced human cathelicidin antimicrobial peptide gene expression.","authors":"Lowry, Malcolm B; Guo, Chunxiao; Zhang, Yang; Fantacone, Mary L; Logan, Isabelle E; Campbell, Yan; Zhang, Weijian; Le, Mai; Indra, Arup K; Ganguli-Indra, Gitali; Xie, Jingwei; Gallo, Richard L; Koeffler, H Phillip; Gombart, Adrian F","year":2020,"journal":"The Journal of steroid biochemistry and molecular biology, 198, 105552","doi":"10.1016/j.jsbmb.2019.105552","pmid":"31783153","tags":["ll-37","antimicrobial-peptides","wound-healing","infection","skin-repair"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"CAMP transgenic mice showed increased Salmonella resistance, restored wound healing in Camp-KO skin, and topical vitamin D induced LL-37 expression with enhanced S. aureus killing in wounds.","whyItMatters":"This is the first animal model linking human vitamin D-cathelicidin biology, enabling research into how vitamin D supplementation could boost antimicrobial defense and wound healing in humans.","specificNumbers":"CAMP expressed in multiple tissues; increased Salmonella resistance; restored wound healing; topical vitamin D increased S. aureus killing","methodology":"Transgenic mouse generation (human CAMP gene crossed with mouse Camp-KO); tissue expression analysis; Salmonella gut colonization challenge; skin wound healing assays; topical vitamin D treatment with S. aureus wound infection model.","limitations":"Mouse model — TLR-vitamin D pathway didn't fully recapitulate human macrophage signaling; species differences in vitamin D metabolism remain; wound model may not reflect chronic human wounds."},{"rthcId":"RPEP-04968","title":"Precursors of thymic peptides as stress sensors.","authors":"Lunin, Sergey; Khrenov, Maxim; Glushkova, Olga; Parfenyuk, Svetlana; Novoselova, Tatyana; Novoselova, E","year":2020,"journal":"Expert opinion on biological therapy, 20(12), 1461-1475","doi":"10.1080/14712598.2020.1800636","pmid":"32700610","tags":["thymosin-alpha-1","thymosin-beta-4","immune-function"],"studyType":"review","evidenceStrength":"low","keyFinding":"Intranuclear precursors of thymic peptides are ubiquitous in somatic cells and may function as stress sensors, releasing immunologically active peptides as cellular distress signals.","whyItMatters":"Understanding how cells communicate damage to the immune system is fundamental to immunology. If thymic peptide precursors are universal stress sensors, this redefines their therapeutic potential.","specificNumbers":"5 thymic hormones reviewed; precursors found in all somatic cell nuclei","methodology":"Theoretical review and synthesis of existing data on thymic peptide precursor biology, immune effects, and neuroendocrine interactions, proposing a novel stress-sensor model.","limitations":"Theoretical/hypothesis-driven review — the stress sensor model is proposed but not experimentally validated; existing data is acknowledged as fragmented."},{"rthcId":"RPEP-04969","title":"The Effects of a Weight-Loss Herbal Formula RCM-107 and Its Eight Individual Ingredients on Glucagon-Like Peptide-1 Secretion-An In Vitro and In Silico Study.","authors":"Luo, Shiqi; Gill, Harsharn; Feltis, Bryce; Hung, Andrew; Nguyen, Linh Toan; Lenon, George Binh","year":2020,"journal":"International journal of molecular sciences, 21(8)","doi":"10.3390/ijms21082854","pmid":"32325890","tags":["glp-1","weight-loss","bioactive-food-peptides"],"studyType":"in-vitro","evidenceStrength":"low","keyFinding":"Gardeniae fructus induced significantly greater GLP-1 secretion than EGCG; molecular docking identified 3-epioleanolic acid and crocin as potential GLP-1 receptor agonists.","whyItMatters":"GLP-1-based drugs (semaglutide, tirzepatide) dominate obesity treatment. Natural compounds that stimulate GLP-1 could offer accessible, low-cost alternatives or complementary approaches.","specificNumbers":"Gardeniae fructus > EGCG for GLP-1 secretion; 2 predicted GLP-1R agonists identified (3-epioleanolic acid, crocin)","methodology":"In vitro GLP-1 secretion assay (ELISA) testing RCM-107 and 8 individual herbs; molecular docking of herbal compounds against the GLP-1 receptor crystal structure.","limitations":"In vitro cell assay only — no in vivo weight loss data; molecular docking predictions need experimental validation; herb dosing and bioavailability not assessed."},{"rthcId":"RPEP-04970","title":"Targeted Chemotherapy for Breast Cancer Using an Intelligent Doxorubicin-Loaded Hexapeptide Hydrogel.","authors":"Luo, Shiyao; Zhu, Ying; Li, Yiping; Chen, Li; Lv, Shunzhong; Zhang, Yuan; Ge, Liang; Zhou, Wenwu","year":2020,"journal":"Journal of biomedical nanotechnology, 16(6), 842-852","doi":"10.1166/jbn.2020.2935","pmid":"33187580","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-04971","title":"Pathological role of excessive DNA as a trigger of keratinocyte proliferation in psoriasis.","authors":"Luo, Y; Hara, T; Kawashima, A; Ishido, Y; Suzuki, S; Ishii, N; Kambara, T; Suzuki, K","year":2020,"journal":"Clinical and experimental immunology, 202(1), 1-10","doi":"10.1111/cei.13455","pmid":"32415989","tags":["ll-37","antimicrobial-peptides","skin-repair","inflammation"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Excess dsDNA fragments triggered psoriasis-like keratinocyte changes; vitamin D blocked this via cathelicidin (CAMP), which was required for the anti-inflammatory effect.","whyItMatters":"Identifies a trigger mechanism for psoriasis (excess DNA) and shows vitamin D's therapeutic effect depends on cathelicidin — explaining why vitamin D analogs work for psoriasis treatment.","specificNumbers":"DNA induced TNF-alpha and IL-1beta; vitamin D inhibited both; CAMP required for protection; dsDNA elevated in psoriatic lesions","methodology":"In vitro: human keratinocytes treated with genomic DNA fragments ± vitamin D; measured TNF-α, IL-1β, HB-EGF, TGF-α, Ki-67, keratins 1/10, CAMP expression. In situ: psoriatic skin tissue analyzed for dsDNA, proliferation markers, and inflammatory mediators.","limitations":"In vitro keratinocyte study + tissue histology — no interventional clinical data; the source of excessive DNA in psoriasis (cell death? NETosis?) not fully explored."},{"rthcId":"RPEP-04972","title":"Antibacterial activities and mechanisms of action of a defensin from manila clam Ruditapes philippinarum.","authors":"Lv, Chengjie; Han, Yijing; Yang, Dinglong; Zhao, Jianmin; Wang, Chunlin; Mu, Changkao","year":2020,"journal":"Fish & shellfish immunology, 103, 266-276","doi":"10.1016/j.fsi.2020.05.025","pmid":"32439511","tags":["antimicrobial-peptides","infection"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Rpdef1α showed broad-spectrum anti-Vibrio activity, biofilm inhibition, membrane permeabilization, and enhanced hemocyte phagocytosis; knockdown increased infection mortality.","whyItMatters":"Biofilm-forming Vibrio infections devastate shellfish aquaculture. A natural defensin that both kills planktonic bacteria and prevents biofilms could inspire new anti-infective strategies.","specificNumbers":"Broad-spectrum anti-Vibrio activity; biofilm inhibition; enhanced phagocytosis and chemotaxis; membrane permeabilization confirmed","methodology":"Gene identification and phylogenetic analysis; qRT-PCR and immunohistochemistry for tissue expression; Vibrio challenge with gene knockdown; antimicrobial assays; biofilm inhibition; SEM and electrochemical membrane analysis; hemocyte phagocytosis and chemotaxis assays.","limitations":"Clam immune system differs significantly from mammals; recombinant peptide may behave differently than native; no mammalian cell toxicity testing; specific MIC values not highlighted."},{"rthcId":"RPEP-04973","title":"Thymosin‑β 4 induces angiogenesis in critical limb ischemia mice via regulating Notch/NF‑κB pathway.","authors":"Lv, Shumin; Cai, Hongwen; Xu, Yifei; Dai, Jin; Rong, Xiqing; Zheng, Lanzhi","year":2020,"journal":"International journal of molecular medicine, 46(4), 1347-1358","doi":"10.3892/ijmm.2020.4701","pmid":"32945357","tags":["thymosin-beta-4","wound-healing","cardiovascular"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"Tβ4 promoted angiogenesis in CLI mice by upregulating VEGFA, Ang2, tie2, CD31, and α-SMA via Notch/NF-κB pathway activation, and reversed the effects of pathway inhibitors.","whyItMatters":"CLI affects millions and often leads to amputation. Tβ4's ability to grow new blood vessels through well-defined pathways makes it a strong candidate for limb salvage therapy.","specificNumbers":"Upregulated Ang2, tie2, VEGFA, CD31, alpha-SMA, N1ICD, Notch3, NF-kB, p-p65; reversed DAPT and BMS effects","methodology":"Lentiviral Tβ4 overexpression in HUVECs and CLI mouse model; Notch inhibitor (DAPT) and NF-κB inhibitor (BMS) used for pathway confirmation; cell viability, tube formation, wound healing, Western blot, qPCR, immunofluorescence, immunohistochemistry.","limitations":"Mouse CLI model — surgical ischemia may not fully replicate chronic human peripheral artery disease; lentiviral overexpression differs from peptide administration; group sizes not specified."},{"rthcId":"RPEP-04974","title":"Peptide-TLR-7/8a conjugate vaccines chemically programmed for nanoparticle self-assembly enhance CD8 T-cell immunity to tumor antigens.","authors":"Lynn, Geoffrey M; Sedlik, Christine; Baharom, Faezzah; Zhu, Yaling; Ramirez-Valdez, Ramiro A; Coble, Vincent L; Tobin, Kennedy; Nichols, Sarah R; Itzkowitz, Yaakov; Zaidi, Neeha; Gammon, Joshua M; Blobel, Nicolas J; Denizeau, Jordan; de la Rochere, Philippe; Francica, Brian J; Decker, Brennan; Maciejewski, Mateusz; Cheung, Justin; Yamane, Hidehiro; Smelkinson, Margery G; Francica, Joseph R; Laga, Richard; Bernstock, Joshua D; Seymour, Leonard W; Drake, Charles G; Jewell, Christopher M; Lantz, Olivier; Piaggio, Eliane; Ishizuka, Andrew S; Seder, Robert A","year":2020,"journal":"Nature biotechnology, 38(3), 320-332","doi":"10.1038/s41587-019-0390-x","pmid":"31932728","tags":["cancer","peptide-design","peptide-delivery","immune-function"],"studyType":"animal","evidenceStrength":"high","keyFinding":"SNP-7/8a self-assembled nanoparticles induced CD8 T cells against ~50% of high-affinity predicted neoantigens (179 tested) and enhanced tumor clearance in three mouse models, with immunogenicity confirmed in primates.","whyItMatters":"This solves the key manufacturing bottleneck for personalized cancer vaccines — one platform that works with any neoantigen — potentially enabling rapid, scalable personalized immunotherapy.","specificNumbers":"~20 nm nanoparticles; 179 neoantigens; ~50% CD8 T cell response rate; enhanced tumor clearance in 3 models; confirmed in NHPs","methodology":"Peptide-TLR-7/8a conjugate chemistry with charge modification; nanoparticle characterization (~20nm); vaccination in 3 mouse tumor models with 179 predicted neoantigens; CD8 T cell response quantification; tumor clearance; non-human primate immunogenicity study.","limitations":"Mouse tumor models with artificially implanted tumors; ~50% immunogenicity means half of predicted neoantigens didn't work; primate study used mock neoantigens, not real tumor antigens; human clinical data needed."},{"rthcId":"RPEP-04975","title":"Developmental and Tissue Patterns of the Basal Expression of Chicken Avian β-Defensins.","authors":"Lyu, Wentao; Zhang, Long; Gong, Yujie; Wen, Xueting; Xiao, Yingping; Yang, Hua","year":2020,"journal":"BioMed research international, 2020, 2567861","doi":"10.1155/2020/2567861","pmid":"33490238","tags":["antimicrobial-peptides","immune-function"],"studyType":"animal","evidenceStrength":"low-moderate","keyFinding":"Chicken β-defensins are upregulated (not downregulated) after hatching, with tissue-specific expression patterns peaking at days 3-14, suggesting essential roles in early innate defense.","whyItMatters":"Understanding when and where defensins are expressed in poultry development could improve disease management strategies for young chicks — the most vulnerable period in poultry farming.","specificNumbers":"14 AvBD genes; 11 tissues; 5 time points; AvBD11 undetected; AvBD5/14 highest in proximal GI; peak expression days 3-14","methodology":"Tissue collection from liver, spleen, and 9 GI segments at days 1, 3, 7, 14, and 28 post-hatching; RNA isolation; qRT-PCR for all 14 AvBD genes.","limitations":"Expression data only (mRNA, not protein levels); broiler chickens may differ from other breeds; environmental/microbial factors not controlled; functional antimicrobial activity not tested."},{"rthcId":"RPEP-04976","title":"Modulation of Sensory Nerve Function by Insulin: Possible Relevance to Pain, Inflammation and Axon Growth.","authors":"Lázár, Bence András; Jancsó, Gábor; Sántha, Péter","year":2020,"journal":"International journal of molecular sciences, 21(7)","doi":"10.3390/ijms21072507","pmid":"32260335","tags":["neuropeptides","pain-management","diabetes"],"studyType":"review","evidenceStrength":"n/a (review)","keyFinding":"Insulin receptors are expressed on a specific subset of sensory neurons in both the central and peripheral nervous system. Quantitative studies revealed that visceral (organ-supplying) sensory neurons express more insulin receptors than somatic (skin/muscle) sensory neurons.\n\nInsR co-localizes with TRPV1 (a pain channel), CGRP, and substance P in these neurons. This co-expression means insulin signaling can directly modulate pain transmission and neurogenic inflammation.\n\nThe functional significance includes modulation of ion channels involved in pain, regulation of neuropeptide release (CGRP and substance P), and neurotrophic effects on nerve growth, development, and regeneration. Recent studies reveal important roles for insulin in axonal growth and repair.","whyItMatters":"Diabetic patients commonly experience altered pain sensitivity and nerve damage (neuropathy). Understanding how insulin directly affects pain-sensing neurons through neuropeptide pathways could explain these symptoms and lead to targeted treatments.\n\nThe finding that visceral sensory neurons are particularly enriched in insulin receptors explains why organs like the pancreas and bladder are especially vulnerable to inflammation in metabolic disease.","specificNumbers":"InsR co-localizes with TRPV1, CGRP, substance P; visceral > somatic InsR expression; modulates pain, inflammation, nerve growth","methodology":"This is a review article summarizing immunohistochemical, electrophysiological, and molecular studies on insulin receptor expression and function in primary sensory neurons, with focus on co-localization with pain-related channels and neuropeptides.","limitations":"This is a review article synthesizing existing data. Many of the findings are from animal studies, and the extent to which they translate to human patients is not fully established.\n\nThe functional consequences of InsR-neuropeptide interactions in specific disease states remain to be directly tested."},{"rthcId":"RPEP-04977","title":"Antimicrobial peptides: bridging innate and adaptive immunity in the pathogenesis of psoriasis.","authors":"Ma, Jing-Yi; Shao, Shuai; Wang, Gang","year":2020,"journal":"Chinese medical journal, 133(24), 2966-2975","doi":"10.1097/CM9.0000000000001240","pmid":"33237697","tags":["antimicrobial-peptides","ll-37","skin-repair","inflammation","immune-function"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"LL-37, defensins, S100 proteins, lipocalin 2, and RNase 7 are highly expressed in psoriatic skin and bridge innate and adaptive immune responses in disease pathogenesis.","whyItMatters":"Understanding how AMPs drive psoriasis — rather than just defend against infection — could lead to targeted therapies that modulate specific AMP functions without compromising antimicrobial defense.","specificNumbers":"LL-37, hBD1-4, S100 proteins, lipocalin 2, RNase 7 all highly expressed in psoriatic lesions","methodology":"Narrative review of recent literature on AMPs in psoriasis, focusing on immunomodulatory mechanisms linking innate and adaptive immunity.","limitations":"Narrative review — no systematic search methodology; mostly mechanistic data from in vitro and animal studies; clinical implications of AMP-targeting therapies largely speculative."},{"rthcId":"RPEP-04978","title":"Development of tumour peptide vaccines: From universalization to personalization.","authors":"Ma, Minjun; Liu, Jingwen; Jin, Shenghang; Wang, Lan","year":2020,"journal":"Scandinavian journal of immunology, 91(6), e12875","doi":"10.1111/sji.12875","pmid":"32090366","tags":["cancer","peptide-design","immune-function","clinical-trials"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Personalized neoantigen peptide vaccines enabled by genomics and bioinformatics represent a paradigm shift from universal tumor vaccines, with checkpoint inhibitor combinations showing enhanced efficacy.","whyItMatters":"Cancer vaccines have historically underperformed in clinical trials. The shift to personalized neoantigen targeting and combination with checkpoint immunotherapy may finally unlock their therapeutic potential.","specificNumbers":"Technologies: NGS, epitope prediction, tetramer assays, CPPs, nanoparticles; combination with checkpoint blockade","methodology":"Narrative review of cancer peptide vaccine development, covering antigen discovery, epitope prediction, delivery technologies, and clinical evolution from shared to personalized antigens.","limitations":"Review — no new data; most personalized vaccine clinical trials are still early-phase; manufacturing complexity and cost remain barriers; neoantigen prediction accuracy still imperfect."},{"rthcId":"RPEP-04979","title":"Protective effects of GHK-Cu in bleomycin-induced pulmonary fibrosis via anti-oxidative stress and anti-inflammation pathways.","authors":"Ma, Wen-Hui; Li, Meng; Ma, Hai-Feng; Li, Wei; Liu, Li; Yin, Yan; Zhou, Xiao-Ming; Hou, Gang","year":2020,"journal":"Life sciences, 241, 117139","doi":"10.1016/j.lfs.2019.117139","pmid":"31809714","tags":["ghk-cu","respiratory","inflammation"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"GHK-Cu inhibited pulmonary fibrosis by reducing TNF-α/IL-6, collagen deposition, and EMT progression through suppression of TGFβ1/Smad2/3 signaling and NF-κB, with Nrf2 pathway activation.","whyItMatters":"IPF kills ~40,000 Americans annually with only two approved drugs (pirfenidone, nintedanib) that slow but don't stop disease. GHK-Cu is a naturally occurring peptide with a strong safety profile that targets the core fibrotic pathway.","specificNumbers":"Doses: 0.2, 2, 20 ug/g/day IP q.o.d.; reduced TNF-alpha, IL-6, MPO; decreased collagen; reversed MMP-9/TIMP-1; modulated Nrf2, NF-kB, TGFb1/Smad2/3","methodology":"Mouse bleomycin-induced pulmonary fibrosis model; GHK-Cu at 0.2, 2, and 20 µg/g/day IP on alternate days for 21 days; histology, BALF cytokine analysis, collagen quantification, EMT markers (α-SMA, fibronectin), Western blot for NF-κB, Nrf2, TGFβ1/Smad2/3.","limitations":"Bleomycin mouse model is acute fibrosis (not the slow progressive fibrosis of human IPF); IP injection route differs from potential clinical routes; long-term outcomes not assessed."},{"rthcId":"RPEP-04980","title":"Antimicrobial peptides of the vaginal innate immunity and their role in the fight against sexually transmitted diseases.","authors":"Madanchi, H; Shoushtari, M; Kashani, H H; Sardari, S","year":2020,"journal":"New microbes and new infections, 34, 100627","doi":"10.1016/j.nmni.2019.100627","pmid":"31993204","tags":["antimicrobial-peptides","ll-37","infection","sexual-health"],"studyType":"review","evidenceStrength":"low-moderate","keyFinding":"Vaginal AMPs (defensins, LL-37, lactoferrin, SLPI, calprotectin, lysozyme, elafin) provide innate defense against STIs; some (LL-37, magainin 2, nisin) have dual spermicidal-antimicrobial activity.","whyItMatters":"Antibiotic-resistant STIs (gonorrhea, chlamydia) are a growing global health crisis. AMPs that the body already produces could be developed into new anti-STI treatments that resist bacterial countermeasures.","specificNumbers":"Key AMPs: defensins, SLPI, calprotectin, lysozyme, lactoferrin, elafin; LL-37, magainin 2, nisin dual activity","methodology":"Narrative review of vaginal innate immunity AMPs, their antimicrobial spectra, immunomodulatory roles, and potential therapeutic applications against sexually transmitted infections.","limitations":"Narrative review with no systematic methodology; most AMP antimicrobial data is in vitro; vaginal pH, microbiome, and hormonal changes affect AMP activity; clinical development challenges remain."},{"rthcId":"RPEP-04981","title":"Design and Synthesis of Lipopolysaccharide-Binding Antimicrobial Peptides Based on Truncated Rabbit and Human CAP18 Peptides and Evaluation of Their Action Mechanism.","authors":"Madanchi, Hamid; Ebrahimi Kiasari, Ramin; Seyed Mousavi, Seyed Javad; Johari, Behrooz; Shabani, Ali Akbar; Sardari, Soroush","year":2020,"journal":"Probiotics and antimicrobial proteins, 12(4), 1582-1593","doi":"10.1007/s12602-020-09648-5","pmid":"32445120","tags":["ll-37","antimicrobial-peptides","peptide-design","infection"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Truncated rCap18 showed superior antimicrobial activity with lower cytotoxicity; truncated hCap18 had better LPS-binding ability; both non-toxic to human fibroblasts at MIC.","whyItMatters":"Shorter peptides are cheaper to manufacture and potentially safer. Having one version optimized for killing bacteria and another for neutralizing LPS toxin expands the therapeutic toolkit.","specificNumbers":"MIC 4-128 ug/mL; hCap18 better LPS binding; rCap18 better antimicrobial, lower cytotoxicity; nontoxic at MIC in human fibroblasts","methodology":"In silico peptide design; solid-phase synthesis; MIC determination; quantitative LAL (LPS-binding) assay; CD spectroscopy; MTT cytotoxicity; hemolysis assay; FE-SEM, confocal microscopy, and flow cytometry for mechanism.","limitations":"In vitro only; limited bacterial panel tested; truncation may alter in vivo stability; no animal infection models; MIC range (4-128 µg/mL) is broad."},{"rthcId":"RPEP-04982","title":"Short-term interval exercise suppresses acylated ghrelin and hunger during caloric restriction in women with obesity.","authors":"Malin, Steven K; Heiston, Emily M; Gilbertson, Nicole M; Eichner, Natalie Z M","year":2020,"journal":"Physiology & behavior, 223, 112978","doi":"10.1016/j.physbeh.2020.112978","pmid":"32473928","tags":["weight-loss","hormone-optimization"],"studyType":"rct","evidenceStrength":"moderate","keyFinding":"LCD+INT suppressed post-prandial acylated ghrelin (P=0.04) and attenuated fasting hunger (P=0.05) compared to energy-matched LCD alone in women with obesity.","whyItMatters":"The biggest barrier to dieting is hunger. Interval exercise suppresses the hunger hormone ghrelin, potentially making calorie restriction more sustainable for weight loss.","specificNumbers":"26 women; BMI 37.3; 2 weeks; acylated ghrelin suppressed (p=0.04); hunger attenuated (p=0.05); PYY increased (p<0.001)","methodology":"RCT: 26 women with obesity randomized to LCD (1,200 kcal/day) or LCD+INT (diet + 60 min/day interval exercise, energy-matched with extra shake). 2-week intervention. OGTT with ghrelin, PYY, des-ghrelin at 0/30/60 min; VAS appetite scales.","limitations":"Small sample (26 women); only 2 weeks — long-term effects unknown; women only; energy matching with post-exercise shake may not reflect real-world behavior; statistical significance borderline for some outcomes."},{"rthcId":"RPEP-04983","title":"Giardia spp. promote the production of antimicrobial peptides and attenuate disease severity induced by attaching and effacing enteropathogens via the induction of the NLRP3 inflammasome.","authors":"Manko-Prykhoda, Anna; Allain, Thibault; Motta, Jean-Paul; Cotton, James A; Feener, Troy; Oyeyemi, Ayodele; Bindra, Sunint; Vallance, Bruce A; Wallace, John L; Beck, Paul; Buret, Andre G","year":2020,"journal":"International journal for parasitology, 50(4), 263-275","doi":"10.1016/j.ijpara.2019.12.011","pmid":"32184085","tags":["antimicrobial-peptides","gut-healing","immune-function","infection"],"studyType":"animal","evidenceStrength":"moderate-high","keyFinding":"Giardia co-infection reduced E. coli-induced colitis via NLRP3-dependent activation of β-defensin 3 and TFF3 antimicrobial peptides; protection was abolished in NLRP3-KO mice.","whyItMatters":"This resolves the \"Giardia paradox\" in global health and reveals that controlled inflammasome activation can boost antimicrobial defense — a potential strategy for preventing bacterial gut infections.","specificNumbers":"Reduced colitis, blood in stool, weight loss, bacterial invasion; elevated beta-defensin 3, TFF3; all NLRP3-dependent","methodology":"Mouse co-infection model (Giardia + Citrobacter rodentium); NLRP3-KO mice; disease severity scoring (colitis, bloody stool, weight loss); AMP expression; bacterial invasion quantification; human enterocyte NLRP3 inhibition experiments.","limitations":"Mouse model using Citrobacter (not actual EPEC/EHEC); Giardia co-infection is not a practical therapeutic strategy; NLRP3 activation also drives inflammation in other contexts."},{"rthcId":"RPEP-04984","title":"Effects of glucagon-like peptide-1 receptor agonists on major cardiovascular events in patients with Type 2 diabetes mellitus with or without established cardiovascular disease: a meta-analysis of randomized controlled trials.","authors":"Marsico, Fabio; Paolillo, Stefania; Gargiulo, Paola; Bruzzese, Dario; Dell'Aversana, Simona; Esposito, Immacolata; Renga, Francesco; Esposito, Luca; Marciano, Caterina; Dellegrottaglie, Santo; Iesu, Ivana; Perrone Filardi, Pasquale","year":2020,"journal":"European heart journal, 41(35), 3346-3358","doi":"10.1093/eurheartj/ehaa082","pmid":"32077924","tags":["glp-1","cardiovascular","diabetes","clinical-trials"],"studyType":"meta-analysis","evidenceStrength":"high","keyFinding":"GLP-1 receptor agonists reduced 3-point MACE by 12% (HR 0.88), stroke by 16%, CV death by 12%, all-cause mortality by 11%, and HF hospitalization by 8% across 56,004 patients — with no significant difference between those with or without established CVD.","whyItMatters":"This is the definitive evidence that GLP-1 drugs save lives in type 2 diabetes — and they should be used even in patients who haven't yet had a heart attack or stroke.","specificNumbers":"MACE HR 0.88; CV death HR 0.88; all-cause mortality HR 0.89; stroke HR 0.84; HF hospitalization HR 0.92; MI HR 0.91 (NS); no excess pancreatitis or pancreatic cancer","methodology":"Trial-level meta-analysis of 7 randomized placebo-controlled cardiovascular outcome trials from PubMed, Embase, Cochrane, Web of Science, SCOPUS, and ClinicalTrials.gov. Cox proportional hazards models; interaction analysis for CVD vs CV risk factors only.","limitations":"Trial-level (not patient-level) meta-analysis; MI reduction narrowly missed significance (HR 0.91, P=0.039 only in sensitivity analysis); individual drugs may differ in efficacy."},{"rthcId":"RPEP-04985","title":"Beyond Fmoc: a review of aromatic peptide capping groups.","authors":"Martin, Adam D; Thordarson, Pall","year":2020,"journal":"Journal of materials chemistry. B, 8(5), 863-877","doi":"10.1039/c9tb02539a","pmid":"31950969","tags":["peptide-design","peptide-delivery"],"studyType":"review","evidenceStrength":"low","keyFinding":"Aromatic capping groups beyond Fmoc enable self-assembling peptide materials with added functions: redox responsiveness, fluorescence, and controlled drug delivery.","whyItMatters":"The capping group determines what a peptide material can DO, not just how it assembles. Smart caps could enable injectable drug-releasing gels, implantable sensors, and responsive tissue engineering scaffolds.","specificNumbers":"Applications: tissue engineering, energy, sensing, drug delivery; Fmoc alternatives with redox, fluorescent, drug-releasing properties","methodology":"Review of recent literature on aromatic N-terminal capping groups for self-assembling peptides, covering chemistry, materials properties, and functional applications.","limitations":"Review — no new experimental data; many functional caps are at proof-of-concept stage; in vivo biocompatibility of non-Fmoc caps not well characterized; manufacturing complexity may increase."},{"rthcId":"RPEP-04986","title":"Association Between Ketosis and Changes in Appetite Markers with Weight Loss Following a Very Low-Energy Diet.","authors":"Martins, Catia; Nymo, Siren; Truby, Helen; Rehfeld, Jens F; Hunter, Gary R; Gower, Barbara A","year":2020,"journal":"Obesity (Silver Spring, Md.), 28(12), 2331-2338","doi":"10.1002/oby.23011","pmid":"33230962","tags":["glp-1","weight-loss","hormone-optimization"],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"Fasting βHB negatively correlated with ghrelin changes (P=0.003) and positively with GLP-1 (P=0.025) and CCK (P=0.035) after 17.7 kg weight loss, but not with subjective appetite.","whyItMatters":"Weight loss typically increases hunger (the body fights back). Ketosis may counteract this by modulating gut hormones, making very low-calorie and ketogenic diets more tolerable.","specificNumbers":"Lost 17.7 kg; BHB 1.24 mmol/L; ghrelin r=-0.315 (p=0.003); GLP-1 r=0.244 (p=0.025); CCK r=0.228 (p=0.035); no PYY correlation","methodology":"Observational study of 87 adults with obesity (BMI 36.5) on 8-week very low-energy diet. Measured at baseline and week 9: body composition, fasting βHB, active ghrelin, GLP-1, PYY, CCK, insulin; subjective appetite by VAS.","limitations":"Observational correlations — cannot prove causation; no non-ketotic control group; subjective appetite didn't correlate with βHB; confounders possible; short follow-up."},{"rthcId":"RPEP-04987","title":"Antiproliferative effects of [D-Pro2, D-Trp7,9]-Substance P and aprepitant on several cancer cell lines and their selectivity in comparison to normal cells.","authors":"Matalińska, Joanna; Świć, Agnieszka; Lipiński, Piotr; Misicka, Aleksandra","year":2020,"journal":"Folia neuropathologica, 58(3), 237-244","doi":"10.5114/fn.2020.100066","pmid":"33099293","tags":["neuropeptides","cancer"],"studyType":"in-vitro","evidenceStrength":"low-moderate","keyFinding":"Aprepitant potently reduced cancer cell proliferation but was not selective (equally toxic to normal cells); the peptide NK-1 antagonist showed minimal anticancer activity even at 100 µM.","whyItMatters":"Challenges the idea that NK-1 receptor blockers are selective cancer treatments. Aprepitant's lack of selectivity limits its potential as an anti-cancer drug despite strong antiproliferative effects.","specificNumbers":"Aprepitant potent in all 5 cancer lines but also in 3 normal lines; peptide antagonist effective only at 100 uM in few lines; no colony formation effect","methodology":"In vitro: 5 cancer + 3 normal cell lines; cell proliferation test, MTT assay, and colony formation assay; aprepitant vs [D-Pro2, D-Trp7,9]-Substance P at multiple concentrations.","limitations":"In vitro only; limited cell line panel; peptide antagonist concentrations may not be pharmacologically relevant; aprepitant's non-selectivity may be dose-dependent."},{"rthcId":"RPEP-04988","title":"A Randomized Controlled Trial of Intranasal Neuropeptide Y in Patients With Major Depressive Disorder.","authors":"Mathé, Aleksander A; Michaneck, Miranda; Berg, Elisabeth; Charney, Dennis S; Murrough, James W","year":2020,"journal":"The international journal of neuropsychopharmacology, 23(12), 783-790","doi":"10.1093/ijnp/pyaa054","pmid":"33009815","tags":["neuropeptides","anxiety-mood","nasal-peptides","clinical-trials"],"studyType":"rct","evidenceStrength":"moderate","keyFinding":"Single-dose intranasal NPY (6.8 mg) reduced MADRS by 10.3 points at 24h vs 5.6 for placebo (P=0.04, d=0.67) in MDD patients; effect not significant at 48h.","whyItMatters":"One-third of depression patients don't respond to existing medications. NPY represents a completely novel mechanism — replacing a brain peptide that's depleted in depression.","specificNumbers":"6.8 mg single dose; MADRS -10.3 vs -5.6 at 24h (p=0.04, d=0.67); -7.1 vs -3.5 at 5h (p=0.05, d=0.61); 48h NS","methodology":"Double-blind RCT: 30 MDD patients on stable antidepressants; 12 received 6.8 mg intranasal NPY, 18 placebo; MADRS assessed at baseline, +1h, +5h, +24h, +48h.","limitations":"Very small sample (n=30, unequal groups 12 vs 18); primary endpoint at 48h not met; single dose — duration of effect unknown with repeated dosing; add-on to antidepressants only."},{"rthcId":"RPEP-04989","title":"Proof of site-specificity of antibody-drug conjugates produced by chemical conjugation technology: AJICAP first generation.","authors":"Matsuda, Yutaka; Malinao, Maria-Christina; Robles, Veronica; Song, James; Yamada, Kei; Mendelsohn, Brian A","year":2020,"journal":"Journal of chromatography. B, Analytical technologies in the biomedical and life sciences, 1140, 121981","doi":"10.1016/j.jchromb.2020.121981","pmid":"32036254","tags":["peptide-design","cancer"],"studyType":"in-vitro","evidenceStrength":"low","keyFinding":"AJICAP conjugation occurs specifically at Lys248 in the Fc region, confirmed by MS/MS and peptide mapping with >93% sequence coverage.","whyItMatters":"ADC manufacturing requires proving where exactly drugs attach to antibodies. AJICAP's confirmed site-specificity enables more consistent, regulatory-compliant cancer drug manufacturing.","specificNumbers":"Lys248 conjugation site; >93% sequence coverage; neutral pH pretreatment; HIC-HPLC purification","methodology":"Peptide mapping with neutral pH pretreatment; MS/MS fragmentation analysis; extracted ion chromatography; preparative HIC-HPLC purification; >93% sequence coverage from single enzymatic digestion.","limitations":"Analytical characterization only — no biological activity or in vivo efficacy data; single antibody tested; manufacturing scale-up not addressed."},{"rthcId":"RPEP-04990","title":"5-aminolevulinic acid inhibits oxidative stress and ameliorates autistic-like behaviors in prenatal valproic acid-exposed rats.","authors":"Matsuo, Kazuya; Yabuki, Yasushi; Fukunaga, Kohji","year":2020,"journal":"Neuropharmacology, 168, 107975","doi":"10.1016/j.neuropharm.2020.107975","pmid":"31991146","tags":["oxytocin","neuroprotection","nasal-peptides"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"5-ALA and intranasal OXT both rescued ASD-like behaviors, but only 5-ALA corrected hippocampal oxidative stress and mitochondrial dysfunction; both restored parvalbumin interneuron numbers.","whyItMatters":"ASD has no approved pharmacological treatment for core symptoms. Understanding that oxytocin and 5-ALA work through complementary mechanisms suggests combination therapy potential.","specificNumbers":"5-ALA 30 mg/kg/day oral; OXT 12 ug/kg/day intranasal; both rescued social/repetitive/memory deficits; only 5-ALA fixed oxidative stress, mitochondrial dysfunction, ATP levels","methodology":"Rat VPA-ASD model (600 mg/kg E12.5); chronic oral 5-ALA (30 mg/kg/day) or intranasal OXT (12 µg/kg/day); behavioral tests (spatial memory, object recognition, social interaction, repetitive behavior); oxidative stress markers; mitochondrial enzyme activity and ATP levels; parvalbumin immunohistochemistry.","limitations":"VPA rat model is one of many ASD models and may not represent all forms of human autism; chronic dosing required; no assessment of dose-response; behavioral rescue doesn't guarantee human translation."},{"rthcId":"RPEP-04991","title":"Bremelanotide: New Drug Approved for Treating Hypoactive Sexual Desire Disorder.","authors":"Mayer, Danielle; Lynch, Sarah E","year":2020,"journal":"The Annals of pharmacotherapy, 54(7), 684-690","doi":"10.1177/1060028019899152","pmid":"31893927","tags":["pt-141","sexual-health","clinical-trials","dosing"],"studyType":"review","evidenceStrength":"high","keyFinding":"Bremelanotide significantly improved desire and reduced HSDD-related distress in Phase 2/3 trials, with nausea (39.9%), flushing (20.4%), and headache (11%) as main side effects.","whyItMatters":"HSDD affects 8-10% of premenopausal women. As only the second FDA-approved treatment (after flibanserin), bremelanotide provides an as-needed option working through a novel brain mechanism.","specificNumbers":"1.75 mg SC; nausea 39.9%, flushing 20.4%, headache 11%; max 1/day, 8/month; significant improvement in desire and desire-related distress","methodology":"Systematic review of Phase 2 and 3 clinical trials from Medline, SCOPUS, EMBASE (1996-2019); 2 Phase 3 and 2 Phase 2 trial reports analyzed.","limitations":"Clinical benefit described as \"modest\" despite statistical significance; high nausea rate (40%); subcutaneous injection may be a barrier; long-term safety data limited; no comparison to flibanserin."},{"rthcId":"RPEP-04992","title":"Spider Venom Peptide Pn3a Inhibition of Primary Afferent High Voltage-Activated Calcium Channels.","authors":"McArthur, Jeffrey R; Munasinghe, Nehan R; Finol-Urdaneta, Rocio K; Adams, David J; Christie, Macdonald J","year":2020,"journal":"Frontiers in pharmacology, 11, 633679","doi":"10.3389/fphar.2020.633679","pmid":"33584315","tags":["venom-peptides","pain","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Pn3a inhibits ~55% of DRG HVA calcium currents and 60-80% of Cav1.2/1.3/2.1/2.2 channels; shows additive inhibition with sub-therapeutic opioids on shared calcium channel targets.","whyItMatters":"Understanding how spider venom peptides interact with opioid pathways could enable new pain treatments using low-dose opioid combinations — reducing addiction risk while maintaining pain relief.","specificNumbers":"10 uM Pn3a: ~55% HVA-ICa block; 60-80% Cav1.2/1.3/2.1/2.2 inhibition; Cav2.2 IC50=3.71 uM; 18mV hyperpolarizing inactivation shift; enhanced with DAMGO; no Cav2.3 effect","methodology":"Whole-cell patch clamp electrophysiology in rat DRG neurons and HEK293 cells expressing individual Cav channels; IC50 determination for Cav2.2; voltage-dependence characterization; opioid co-application experiments.","limitations":"In vitro electrophysiology only; Pn3a concentrations needed are high (µM range); selectivity concerns with blocking multiple Cav channels; no in vivo pain model data in this study."},{"rthcId":"RPEP-04993","title":"Heat stress during development affects immunocompetence in workers, queens and drones of Africanized honey bees (Apis mellifera L.) (Hymenoptera: Apidae).","authors":"Medina, Rubén G; Paxton, Robert J; Hernández-Sotomayor, S M Teresa; Pech-Jiménez, Cristina; Medina-Medina, Luis A; Quezada-Euán, José Javier G","year":2020,"journal":"Journal of thermal biology, 89, 102541","doi":"10.1016/j.jtherbio.2020.102541","pmid":"32364969","tags":["antimicrobial-peptides","immune-function"],"studyType":"animal","evidenceStrength":"low-moderate","keyFinding":"Heat stress during pupal development significantly decreased phenoloxidase immune activity in queen bees but not workers or drones, revealing caste-specific vulnerability to temperature-induced immune suppression.","whyItMatters":"As global temperatures rise, understanding how heat stress compromises bee immune systems — particularly their antimicrobial peptide defenses — is critical for predicting colony health and pollinator survival.","specificNumbers":"Heat stress decreased PO in queens; workers highest baseline PO; heat-stressed workers shorter survival post-infection; drones increased PO after infection","methodology":"Controlled animal experiment exposing Africanized honey bee pupae to elevated temperatures, then measuring phenoloxidase activity and survival after fungal infection across workers, queens, and drones.","limitations":"Limited to one bee subspecies (Africanized honey bees); did not directly measure defensin peptide levels; laboratory conditions may not fully replicate field heat stress patterns."},{"rthcId":"RPEP-04994","title":"Peptide-based combination nanoformulations for cancer therapy.","authors":"Mehrotra, Neha; Kharbanda, Surender; Singh, Harpal","year":2020,"journal":"Nanomedicine (London, England), 15(22), 2201-2217","doi":"10.2217/nnm-2020-0220","pmid":"32914691","tags":["cancer","peptide-delivery","cell-penetrating"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Peptide-based nanoformulations can enhance cancer treatment efficacy by improving tumor penetration, increasing circulation time, and reducing off-target toxicity when combined with conventional therapies.","whyItMatters":"Cancer treatment often suffers from severe side effects and drug resistance. Peptide nanoformulations offer a way to deliver targeted therapies more precisely, potentially improving outcomes while reducing harm.","specificNumbers":"Covers: anticancer peptides, CPPs, tumor-targeting, peptidomimetics, peptide hormones, vaccines + chemo/immuno/radiation/hormone therapy","methodology":"Narrative review surveying recent research on nanodelivery systems for peptide-based combination cancer therapies, including chemo-, immuno-, radiation, and hormone therapy combinations.","limitations":"As a review, it summarizes existing research without generating new data; many nanoformulation approaches discussed remain preclinical; clinical translation challenges are significant."},{"rthcId":"RPEP-04995","title":"Pharmacokinetic tuning of protein-antigen fusions enhances the immunogenicity of T-cell vaccines.","authors":"Mehta, Naveen K; Pradhan, Roma V; Soleimany, Ava P; Moynihan, Kelly D; Rothschilds, Adrienne M; Momin, Noor; Rakhra, Kavya; Mata-Fink, Jordi; Bhatia, Sangeeta N; Wittrup, K Dane; Irvine, Darrell J","year":2020,"journal":"Nature biomedical engineering, 4(6), 636-648","doi":"10.1038/s41551-020-0563-4","pmid":"32483299","tags":["cancer","peptide-design","immune-function","clinical-trials"],"studyType":"animal","evidenceStrength":"high","keyFinding":"Protein-peptide epitope fusions using transthyretin as a carrier increased T-cell vaccine immunogenicity by up to 90-fold by optimizing antigen delivery, stability, and lymphatic targeting.","whyItMatters":"Peptide cancer vaccines have consistently underperformed in clinical trials. This fusion strategy addresses fundamental pharmacokinetic weaknesses that limit their effectiveness, potentially transforming cancer immunotherapy.","specificNumbers":"Up to 90-fold immunogenicity increase; transthyretin optimal carrier; 3 PK factors optimized; multiple antigen types validated","methodology":"Preclinical animal study in immunized mice comparing peptide vaccines alone versus peptide-protein fusions, measuring T-cell responses across multiple antigen types.","limitations":"Mouse model only; human immune responses may differ; clinical translation requires safety and efficacy testing; transthyretin carrier may have its own pharmacokinetic considerations in humans."},{"rthcId":"RPEP-04996","title":"Melittin: a venom-derived peptide with promising anti-viral properties.","authors":"Memariani, Hamed; Memariani, Mojtaba; Moravvej, Hamideh; Shahidi-Dadras, Mohammad","year":2020,"journal":"European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology, 39(1), 5-17","doi":"10.1007/s10096-019-03674-0","pmid":"31422545","tags":["venom-peptides","antimicrobial-peptides","infection"],"studyType":"review","evidenceStrength":"low-moderate","keyFinding":"Melittin demonstrates antiviral activity against at least nine different viruses spanning multiple families, suggesting broad-spectrum potential as a venom-derived antiviral peptide.","whyItMatters":"Viral infections remain a leading cause of death globally, and drug resistance is growing. Natural venom peptides like melittin could offer new antiviral mechanisms that complement existing treatments.","specificNumbers":"Active against 9+ viruses; properties: anti-cancer, anti-inflammatory, anti-diabetic, adjuvant; safety challenges significant","methodology":"Narrative review synthesizing experimental studies on melittin antiviral activity conducted over several decades.","limitations":"Most evidence is from in-vitro studies; melittin is cytotoxic at higher concentrations; safety profile for therapeutic use is unclear; molecular mechanisms remain poorly characterized."},{"rthcId":"RPEP-04997","title":"Mitochondrial-derived peptides in energy metabolism.","authors":"Merry, Troy L; Chan, Alex; Woodhead, Jonathan S T; Reynolds, Joseph C; Kumagai, Hiroshi; Kim, Su-Jeong; Lee, Changhan","year":2020,"journal":"American journal of physiology. Endocrinology and metabolism, 319(4), E659-E666","doi":"10.1152/ajpendo.00249.2020","pmid":"32776825","tags":["anti-aging","diabetes","hormone-optimization","receptor-signaling"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Mitochondrial-derived peptides serve as retrograde metabolic signals — declining in metabolic disease but rising during adaptive stress responses like exercise — and can improve insulin sensitivity when administered therapeutically.","whyItMatters":"Understanding MDPs opens a new frontier in metabolic medicine — these peptides represent a built-in cellular signaling system that could be harnessed to treat diabetes, obesity, and age-related metabolic decline.","specificNumbers":"8 MDPs; encoded in 12S and 16S rRNA genes; decreased in obesity, diabetes, aging; increased in exercising muscle; improved insulin sensitivity in rodents","methodology":"Comprehensive review of human observational and rodent interventional studies on mitochondrial-derived peptides and their roles in energy metabolism.","limitations":"Most therapeutic evidence is from rodent models; circulating MDP measurements in humans are still being standardized; tissue-specific responses are not fully characterized."},{"rthcId":"RPEP-04998","title":"Contribution of NPY Y5 Receptors to the Reversible Structural Remodeling of Basolateral Amygdala Dendrites in Male Rats Associated with NPY-Mediated Stress Resilience.","authors":"Michaelson, Sheldon D; Miranda Tapia, Ana Pamela; McKinty, Amanda; Silveira Villarroel, Heika; Mackay, James P; Urban, Janice H; Colmers, William F","year":2020,"journal":"The Journal of neuroscience : the official journal of the Society for Neuroscience, 40(16), 3231-3249","doi":"10.1523/JNEUROSCI.2621-19.2020","pmid":"32144180","tags":["neuropeptides","anxiety-mood"],"studyType":"animal","evidenceStrength":"moderate-high","keyFinding":"NPY acts through Y5 receptors to cause dendritic hypotrophy in amygdala neurons, reducing excitability and anxiety behavior, while reversing CRF-induced structural hypertrophy — a mechanism for stress resilience.","whyItMatters":"This reveals a physical mechanism for stress resilience — NPY literally reshapes brain circuits to be less reactive to stress, pointing toward potential neuropeptide-based treatments for anxiety and PTSD.","specificNumbers":"Y5 receptor activation: dendritic hypotrophy, reduced excitability; reversed CRF effects; calcineurin-dependent; increased social interaction in vivo; Y5 antagonist blocked all effects","methodology":"Combined approach using organotypic slice cultures of male rat basolateral amygdala and in-vivo intra-BLA injections, measuring dendritic morphology, excitatory input, and social interaction behavior.","limitations":"Male rats only; organotypic cultures do not fully replicate in-vivo neural circuits; translation to human anxiety disorders requires further investigation; long-term effects not assessed."},{"rthcId":"RPEP-04999","title":"Abaloparatide: an anabolic treatment to reduce fracture risk in postmenopausal women with osteoporosis.","authors":"Miller, Paul D; Bilezikian, John P; Fitzpatrick, Lorraine A; Mitlak, Bruce; McCloskey, Eugene V; Cosman, Felicia; Bone, Henry G","year":2020,"journal":"Current medical research and opinion, 36(11), 1861-1872","doi":"10.1080/03007995.2020.1824897","pmid":"32969719","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05000","title":"Newly synthesized peptide, Ara-27, exhibits significant improvement in cell-penetrating ability compared to conventional peptides.","authors":"Min, Sol; Kim, Kichul; Ku, Seockmo; Park, Jeong-Yoon; Seo, Jeongmin; Roh, Sangho","year":2020,"journal":"Biotechnology progress, 36(5), e3014","doi":"10.1002/btpr.3014","pmid":"32374475","tags":["cell-penetrating","peptide-delivery","peptide-design"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Ara-27 achieved >99% cell-penetrating efficiency at 2 μM in human cells compared to <10% for Tat-PTD and MTS, with 8-22x higher intracellular fluorescence intensity.","whyItMatters":"Getting drugs and molecules inside cells is a major challenge in medicine. A CPP that works at low concentrations with near-complete efficiency could transform drug delivery for gene therapies, siRNA, and small molecules.","specificNumbers":">99% penetration at 2 uM (Ara-27) vs <10% (TAT, MTS); 8-22x fluorescence intensity; internalized at 0.2 uM; no cytotoxicity","methodology":"In-vitro comparison study using flow cytometry and confocal microscopy to measure FITC-labeled peptide uptake in human dermal fibroblasts and dental pulp stem cells.","limitations":"In-vitro study only with two human cell types; no in-vivo testing; cargo delivery efficiency not tested; mechanism of enhanced uptake not fully characterized."},{"rthcId":"RPEP-05001","title":"Optimal dietary curcumin improved growth performance, and modulated innate immunity, antioxidant capacity and related genes expression of NF-κB and Nrf2 signaling pathways in grass carp (Ctenopharyngodon idella) after infection with Aeromonas hydrophila.","authors":"Ming, Jianhua; Ye, Jinyun; Zhang, Yixiang; Xu, Qiyou; Yang, Xia; Shao, Xianping; Qiang, Jun; Xu, Pao","year":2020,"journal":"Fish & shellfish immunology, 97, 540-553","doi":"10.1016/j.fsi.2019.12.074","pmid":"31881329","tags":["antimicrobial-peptides","immune-function","bioactive-food-peptides"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"Optimal dietary curcumin (438 mg/kg) upregulated antimicrobial peptides hepcidin, LEAP-2, and β-defensin while activating Nrf2 antioxidant pathways and suppressing NF-κB inflammatory signaling after bacterial challenge.","whyItMatters":"Demonstrates that dietary compounds can upregulate endogenous antimicrobial peptide production, offering a nutritional strategy to boost innate immunity — relevant to both aquaculture and broader immunology.","specificNumbers":"Optimal 394 mg/kg; improved WG, SGR, FCR; reduced mortality; upregulated hepcidin, LEAP-2, beta-defensin, IL-10, TGF-beta1; downregulated TNF-alpha, IL-1beta, IL-6, NF-kB p65; optimal requirement 438 mg/kg","methodology":"Controlled feeding trial with 525 juvenile grass carp across 5 curcumin dose groups (3 replicates each) for 60 days, followed by bacterial challenge with Aeromonas hydrophila and measurement of immune, antioxidant, and gene expression markers.","limitations":"Fish model — results may not directly translate to mammals; single bacterial pathogen challenge; 60-day duration may not capture long-term effects; excessive curcumin showed negative effects."},{"rthcId":"RPEP-05002","title":"Pentadecapeptide BPC 157 shortens duration of tetracaine- and oxybuprocaine-induced corneal anesthesia in rats.","authors":"Mirković, Ivan; Kralj, Tamara; Lozić, Marin; Stambolija, Vasilije; Kovačević, Josip; Vrdoljak, Luka; Zlatar, Mirna; Milanović, Kristina; Drmić, Domagoj; Predović, Jurica; Masnec, Sanja; Jurjević, Matija; Bušić, Mladen; Seiwerth, Sven; Kokot, Antonio; Sikirić, Predrag","year":2020,"journal":"Acta clinica Croatica, 59(3), 394-406","doi":"10.20471/acc.2020.59.03.02","pmid":"34177048","tags":["bpc-157","eye-health","wound-healing"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"BPC-157 eye drops (0.4 μg/eye) fully counteracted tetracaine and oxybuprocaine corneal effects — restoring sensitivity, healing lesions, and normalizing tear production — even when the NO system was blocked.","whyItMatters":"Corneal anesthetics are widely used in ophthalmology but cause temporary damage. A peptide eye drop that accelerates recovery could improve patient comfort and safety after eye procedures.","specificNumbers":"BPC-157 0.4 ug/eye; full counteraction of corneal insensitivity, lesions, tear reduction; effective with L-NAME or L-arginine co-administration","methodology":"Controlled rat study measuring corneal sensitivity (Cochet-Bonnet esthesiometer), corneal lesions (fluorescein staining), and tear volume (Schirmer test) after anesthetic application with BPC-157 and NO pathway modulators.","limitations":"Rat model only; single BPC-157 dose tested; no long-term safety data for ocular BPC-157 use; mechanism beyond NO pathway involvement not fully elucidated."},{"rthcId":"RPEP-05003","title":"The mitochondria-targeted peptide SS-31 binds lipid bilayers and modulates surface electrostatics as a key component of its mechanism of action.","authors":"Mitchell, Wayne; Ng, Emily A; Tamucci, Jeffrey D; Boyd, Kevin J; Sathappa, Murugappan; Coscia, Adrian; Pan, Meixia; Han, Xianlin; Eddy, Nicholas A; May, Eric R; Szeto, Hazel H; Alder, Nathan N","year":2020,"journal":"The Journal of biological chemistry, 295(21), 7452-7469","doi":"10.1074/jbc.RA119.012094","pmid":"32273339","tags":["peptide-design","receptor-signaling","anti-aging"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"SS-31 partitions into the mitochondrial membrane interface and modulates surface electrostatics in a charge-dependent manner, with demonstrated reduction of calcium stress as a proof-of-concept protective mechanism.","whyItMatters":"Understanding exactly how SS-31 interacts with mitochondrial membranes enables rational design of improved variants — critical since elamipretide is already in clinical trials for mitochondrial diseases.","specificNumbers":"Binding proportional to surface charge; no bilayer destabilization; altered lipid packing; reduced calcium stress in mitochondria","methodology":"Biophysical and computational study using model lipid bilayers and mitochondrial membranes to characterize SS-31 binding, membrane effects, and calcium distribution.","limitations":"In-vitro study using model membranes; in-vivo membrane conditions are more complex; calcium modulation shown as proof of concept but not fully characterized in living cells."},{"rthcId":"RPEP-05004","title":"Development of peptide therapeutics: A nonclinical safety assessment perspective.","authors":"Mitra, Mayur S; DeMarco, Steven; Holub, Brad; Thiruneelakantapillai, Lakshmanan; Thackaberry, Evan A","year":2020,"journal":"Regulatory toxicology and pharmacology : RTP, 117, 104766","doi":"10.1016/j.yrtph.2020.104766","pmid":"32827570","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05005","title":"Endosomal Escape of Peptide-Photosensitizer Conjugates Is Affected by Amino Acid Sequences near the Photosensitizer.","authors":"Miyoshi, Yuichi; Kadono, Maho; Okazaki, Shigetoshi; Nishimura, Ayano; Kitamatsu, Mizuki; Watanabe, Kazunori; Ohtsuki, Takashi","year":2020,"journal":"Bioconjugate chemistry, 31(3), 916-922","doi":"10.1021/acs.bioconjchem.0c00046","pmid":"32027488","tags":["cell-penetrating","peptide-design","peptide-delivery"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Hydrophobic amino acid linkers (FF and LL) adjacent to the photosensitizer significantly enhanced photochemical internalization efficiency in CPP-cargo-PS conjugates across multiple cargo types.","whyItMatters":"Endosomal trapping is a major bottleneck in peptide drug delivery. This design principle for improving light-triggered escape could make CPP-based therapies more effective.","specificNumbers":"FF and LL linkers enhanced PCI; tested with TatBim-PS and TatU1A-PS; cargo and PS dependent","methodology":"In-vitro study systematically testing different amino acid linker sequences in CPP-cargo-photosensitizer conjugates and measuring photochemical internalization efficiency in mammalian cells.","limitations":"In-vitro only; linker effects varied with cargo and photosensitizer — not universally applicable; PCI requires light activation, limiting deep-tissue applications."},{"rthcId":"RPEP-05006","title":"SialoPen peptides are new cationic foldamers with remarkable cell permeability.","authors":"Monreal, I Abrrey; Contreras, Erik M; Wayman, Gary A; Aguilar, Hector C; Saludes, Jonel P","year":2020,"journal":"Heliyon, 6(12), e05780","doi":"10.1016/j.heliyon.2020.e05780","pmid":"33409387","tags":["cell-penetrating","peptide-design","neuroprotection"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"SialoPen peptides — de novo designed foldamers using a Neu2en scaffold — demonstrated significantly superior cellular uptake compared to classical CPPs penetratin and HIV-TAT in both HeLa and neuronal cells.","whyItMatters":"Many potential drugs cannot cross cell membranes. SialoPen peptides offer a new delivery platform with better penetration than existing options, potentially unlocking previously inaccessible intracellular drug targets.","specificNumbers":"Superior uptake vs penetratin and TAT; confirmed by flow cytometry and confocal; Fmoc SPPS compatible; enhanced biostability","methodology":"In-vitro study using flow cytometry and live-cell confocal microscopy to compare uptake of SialoPen peptides versus penetratin and HIV-TAT in HeLa cells and primary hippocampal neurons.","limitations":"In-vitro study with two cell types only; no in-vivo data; cargo delivery not tested; long-term cytotoxicity not fully characterized."},{"rthcId":"RPEP-05007","title":"Anti-Müllerian Hormone and Ovarian Reserve: Update on Assessing Ovarian Function.","authors":"Moolhuijsen, Loes M E; Visser, Jenny A","year":2020,"journal":"The Journal of clinical endocrinology and metabolism, 105(11), 3361-73","doi":"10.1210/clinem/dgaa513","pmid":"32770239","tags":["peptide-hormones"],"studyType":"review","evidenceStrength":"review","keyFinding":"Anti-Müllerian hormone (AMH) remains the preferred blood marker for assessing functional ovarian reserve — the pool of growing follicles that could potentially lead to ovulation. Serum AMH is used to personalize fertility drug dosing and can predict the risk of poor response or ovarian hyperstimulation during IVF, though it has limited ability to predict actual pregnancy success.\n\nAMH may also help predict when a woman will reach menopause, though the rate of age-related AMH decline varies significantly between individuals. A major ongoing limitation is the lack of an international standard for AMH measurement, making it difficult to compare results across different lab tests.","whyItMatters":"AMH testing has become a cornerstone of fertility medicine, influencing treatment decisions for millions of women undergoing IVF and fertility assessments. Understanding what AMH can and cannot tell clinicians is critical — it's excellent for gauging ovarian reserve and drug dosing but shouldn't be over-interpreted as a pregnancy predictor. The lack of standardized assays means results from different labs may not be directly comparable, which affects clinical decision-making.","specificNumbers":"AMH reflects functional ovarian reserve · Used in individualized FSH dosing · Predicts poor response and hyperstimulation risk · Limited value for predicting ongoing pregnancy · No international measurement standard","methodology":"Systematic literature review using PubMed to identify recent publications on serum AMH measurement and its clinical applications in ovarian reserve assessment.","limitations":"The review highlights that AMH assay standardization remains unresolved — different tests can give different values for the same sample. Little is known about endogenous and exogenous factors (like medications, BMI, or ethnicity) that influence AMH levels. The review itself is limited to published literature and may not capture all emerging assay technologies."},{"rthcId":"RPEP-05008","title":"Clinical Evidence and Mechanisms of High-Protein Diet-Induced Weight Loss.","authors":"Moon, Jaecheol; Koh, Gwanpyo","year":2020,"journal":"Journal of obesity & metabolic syndrome, 29(3), 166-173","doi":"10.7570/jomes20028","pmid":"32699189","tags":["glp-1","weight-loss"],"studyType":"review","evidenceStrength":"moderate-high","keyFinding":"High-protein diets increase anorexigenic gut peptides (GLP-1, CCK, PYY) and decrease ghrelin, combined with higher diet-induced thermogenesis and muscle preservation, producing sustained weight loss in clinical trials.","whyItMatters":"Obesity is a global health crisis. Understanding how dietary protein modulates appetite-regulating peptides provides an evidence-based, drug-free approach to weight management.","specificNumbers":"6-12 month trials; increased GLP-1, CCK, PYY; decreased ghrelin; higher DIT; preserved FFM; no bone/kidney harm in healthy adults","methodology":"Review of clinical trials spanning 6-12 months examining high-protein diet effects on body weight, body composition, satiety hormones, and energy expenditure.","limitations":"Most trials lasted only 6-12 months; long-term effects beyond 12 months unclear; applicability to people with existing kidney disease not established; optimal protein amounts vary by individual."},{"rthcId":"RPEP-05009","title":"Neurokinin-1 Receptor Signaling Is Required for Efficient Ca2+ Flux in T-Cell-Receptor-Activated T Cells.","authors":"Morelli, Adrian E; Sumpter, Tina L; Rojas-Canales, Darling M; Bandyopadhyay, Mohna; Chen, Zhizhao; Tkacheva, Olga; Shufesky, William J; Wallace, Callen T; Watkins, Simon C; Berger, Alexandra; Paige, Christopher J; Falo, Louis D; Larregina, Adriana T","year":2020,"journal":"Cell reports, 30(10), 3448-3465.e8","doi":"10.1016/j.celrep.2020.02.054","pmid":"32160549","tags":["neuropeptides","immune-function","receptor-signaling"],"studyType":"animal","evidenceStrength":"moderate-high","keyFinding":"NK1R and its neuropeptide agonists (substance P, hemokinin-1) localize at the immune synapse and are required for efficient calcium flux, activated T cell survival, and Th1/Th17 pro-inflammatory bias.","whyItMatters":"This reveals a critical neuroimmune connection — neuropeptides directly regulate T cell activation, linking the nervous and immune systems with implications for immunotherapy and inflammatory disease treatment.","specificNumbers":"NK1R/SP co-localize at immune synapse; dual TCR+NK1R required for Ca2+ flux; NK1R-KO T cells: high mortality, impaired Th1/Th17, impaired contact dermatitis","methodology":"Animal study using NK1R-deficient mice and in-vitro T cell activation assays, with confocal imaging of immune synapses and calcium flux measurements, validated in a contact dermatitis model.","limitations":"Mouse model — human translation needs confirmation; contact dermatitis is one disease model; the relative contribution of substance P versus hemokinin-1 in different contexts is unclear."},{"rthcId":"RPEP-05010","title":"A biocompatible stapling reaction for in situ generation of constrained peptides.","authors":"Morewood, Richard; Nitsche, Christoph","year":2020,"journal":"Chemical science, 12(2), 669-674","doi":"10.1039/d0sc05125j","pmid":"34163798","tags":["cyclic-peptides","peptide-design","infection"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"A biocompatible two-component stapling reaction enables in-situ generation of constrained peptides in aqueous solution, with a stapled Zika protease inhibitor showing 28-fold improved potency over its linear analogue.","whyItMatters":"Constrained peptides are more drug-like but hard to make and screen. A biocompatible stapling method that works in biochemical conditions dramatically accelerates drug discovery for peptide therapeutics.","specificNumbers":">28-fold improved inhibition; aqueous pH 7 reaction; on-resin or post-purification stapling; orthogonal to natural amino acids","methodology":"In-vitro chemistry development and screening study testing a new stapling reaction on solid-phase and in solution, validated by screening constrained peptides against Zika NS2B-NS3 protease.","limitations":"In-vitro proof of concept only; Zika protease is one target — breadth of applicability needs demonstration; in-vivo pharmacokinetics of stapled products not tested."},{"rthcId":"RPEP-05011","title":"Effectiveness of dulaglutide vs liraglutide and exenatide once-weekly. A real-world study and meta-analysis of observational studies.","authors":"Morieri, Mario Luca; Rigato, Mauro; Frison, Vera; Simioni, Natalino; D'Ambrosio, Michele; Tadiotto, Federica; Paccagnella, Agostino; Lapolla, Annunziata; Avogaro, Angelo; Fadini, Gian Paolo","year":2020,"journal":"Metabolism: clinical and experimental, 106, 154190","doi":"10.1016/j.metabol.2020.154190","pmid":"32109448","tags":["dulaglutide","liraglutide","exenatide","glp-1","diabetes"],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"Dulaglutide reduced HbA1c 0.24% more than liraglutide in real-world clinical practice (p=0.003), confirmed by meta-analysis of observational studies.","whyItMatters":"Real-world data often differs from clinical trials. This study helps clinicians choose between GLP-1 drugs based on actual patient outcomes in routine care, not just idealized trial settings.","specificNumbers":"Dulaglutide vs liraglutide: -0.24% HbA1c (p=0.003); meta-analysis vs exeOW: -0.19% HbA1c (p=0.003), -0.8 kg (p=0.007); 5.9 month follow-up","methodology":"Retrospective multicenter real-world study (2010-2018) with propensity score matching, plus meta-analysis of similar observational studies covering the same drug comparisons.","limitations":"Observational design with potential residual confounding; liraglutide under-dosing likely influenced results; exenatide group was small (n=198); short follow-up of ~6 months."},{"rthcId":"RPEP-05012","title":"Nephroprotective effects of GLP-1 receptor agonists: where do we stand?","authors":"Mosterd, Charlotte M; Bjornstad, Petter; van Raalte, Daniël H","year":2020,"journal":"Journal of nephrology, 33(5), 965-975","doi":"10.1007/s40620-020-00738-9","pmid":"32356231","tags":["glp-1","kidney","diabetes","semaglutide"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"GLP-1 receptor agonists reduce macro-albuminuria in cardiovascular safety trials, with multiple proposed kidney-protective mechanisms including anti-inflammatory, hemodynamic, and metabolic effects.","whyItMatters":"Diabetic kidney disease is a leading cause of kidney failure with limited treatment options. If GLP-1 drugs protect kidneys beyond their metabolic effects, millions of diabetes patients could benefit.","specificNumbers":"Reduced macro-albuminuria in CVOTs; mechanisms: glycemia, weight, BP, lipids, sodium, inflammation, hypoxia; FLOW trial initiated","methodology":"Narrative review of cardiovascular outcome trial data and preclinical evidence examining GLP-1 receptor agonist effects on kidney function and albuminuria.","limitations":"Kidney findings were secondary/exploratory endpoints in cardiovascular trials; hard renal outcomes not yet tested (at time of publication); mechanisms not fully proven in humans."},{"rthcId":"RPEP-05013","title":"Amylin and pramlintide modulate γ-secretase level and APP processing in lipid rafts.","authors":"Mousa, Youssef M; Abdallah, Ihab M; Hwang, Misako; Martin, Douglas R; Kaddoumi, Amal","year":2020,"journal":"Scientific reports, 10(1), 3751","doi":"10.1038/s41598-020-60664-5","pmid":"32111883","tags":["neuroprotection","diabetes","next-gen-agonists","peptide-safety"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"Amylin and pramlintide increased amyloid-beta production by modulating APP and γ-secretase in lipid rafts, leading to increased Aβ burden, synaptic loss, and neuroinflammation in TgSwDI Alzheimer's mice.","whyItMatters":"Pramlintide is used clinically for diabetes, and amylin is being explored for various metabolic conditions. If these peptides worsen Alzheimer's pathology, it has significant safety implications for millions of patients.","specificNumbers":"30 days IP; increased Aβ; shifted APP/gamma-secretase to lipid rafts; increased B4GALNT1, GM1, GM2 (pramlintide); synaptic loss, apoptosis, microglia activation","methodology":"Animal study using TgSwDI transgenic mice (Alzheimer's/cerebral amyloid angiopathy model) receiving 30 days of intraperitoneal amylin or pramlintide injections, with assessment of Aβ pathology and mechanistic analysis.","limitations":"Transgenic Alzheimer's mouse model may not perfectly reflect human disease; 30-day treatment period; single dose level; other studies have reported opposite (protective) effects of amylin analogs."},{"rthcId":"RPEP-05014","title":"Human VGF-Derived Antidepressant Neuropeptide TLQP62 Promotes SH-SY5Y Neurite Outgrowth.","authors":"Moutinho, Daniela; Veiga, Sónia; Requena, Jesús R","year":2020,"journal":"Journal of molecular neuroscience : MN, 70(8), 1293-1302","doi":"10.1007/s12031-020-01541-8","pmid":"32458204","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05015","title":"Mapping the Molecular Surface of the Analgesic NaV1.7-Selective Peptide Pn3a Reveals Residues Essential for Membrane and Channel Interactions.","authors":"Mueller, Alexander; Dekan, Zoltan; Kaas, Quentin; Agwa, Akello J; Starobova, Hana; Alewood, Paul F; Schroeder, Christina I; Mobli, Mehdi; Deuis, Jennifer R; Vetter, Irina","year":2020,"journal":"ACS pharmacology & translational science, 3(3), 535-546","doi":"10.1021/acsptsci.0c00002","pmid":"32566918","tags":["venom-peptides","pain","peptide-design","receptor-signaling"],"studyType":"animal","evidenceStrength":"moderate-high","keyFinding":"The Pn3a[D8N] mutation increased NaV1.7 inhibition potency 20-fold while maintaining >100-fold selectivity over NaV1.4, NaV1.5, and NaV1.6, with confirmed analgesic activity at lower doses in vivo.","whyItMatters":"NaV1.7 is a validated pain target with strong human genetic evidence. Engineering more potent and selective peptide inhibitors brings us closer to non-opioid pain therapeutics.","specificNumbers":"D8N: 20-fold potency; >100-fold selectivity over NaV1.4/1.5/1.6; 3-fold lower dose in vivo; K22/K24 essential; Y4/Y27/W30 >250-fold loss","methodology":"Rational peptide engineering with 17 Pn3a analogues tested via patch-clamp electrophysiology, molecular modeling of channel interactions, and in-vivo postsurgical pain model in mice.","limitations":"Mouse pain model — human translation needed; peptide delivery challenges for clinical use; long-term safety not assessed; D8N improvement is still preclinical."},{"rthcId":"RPEP-05016","title":"GLP-1 receptor agonists for Parkinson's disease.","authors":"Mulvaney, Caroline A; Duarte, Gonçalo S; Handley, Joel; Evans, David Jw; Menon, Suresh; Wyse, Richard; Emsley, Hedley Ca","year":2020,"journal":"The Cochrane database of systematic reviews, 7(7), CD012990","doi":"10.1002/14651858.CD012990.pub2","pmid":"32700772","tags":["glp-1","exenatide","neuroprotection","clinical-trials"],"studyType":"systematic-review","evidenceStrength":"low","keyFinding":"Exenatide improved MDS-UPDRS Part III motor scores by 3.1-5.6 points versus controls, with effects persisting after drug cessation, but evidence certainty remains low.","whyItMatters":"No existing Parkinson's drug slows disease progression. If GLP-1 agonists are truly disease-modifying — as persistence of effects after cessation suggests — it would be a breakthrough in neurodegenerative disease treatment.","specificNumbers":"MD -3.10 (MDS-UPDRS III, off-med); adjusted MD -3.5 (exceeds MCID); 62 + 45 patients; low/very low certainty; SAEs unrelated; no HRQoL improvement","methodology":"Cochrane systematic review of randomized controlled trials comparing GLP-1 receptor agonists versus placebo or no treatment in Parkinson's disease, with GRADE quality assessment.","limitations":"Only 2 small trials available (107 patients total); low to very low certainty evidence; limited follow-up; quality of life and non-motor outcomes unclear; both trials tested exenatide only."},{"rthcId":"RPEP-05017","title":"Harnessing cyclotides to design and develop novel peptide GPCR ligands.","authors":"Muratspahić, Edin; Koehbach, Johannes; Gruber, Christian W; Craik, David J","year":2020,"journal":"RSC chemical biology, 1(4), 177-191","doi":"10.1039/d0cb00062k","pmid":"34458757","tags":["cyclic-peptides","peptide-design","bioavailability","oral-peptides"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Molecular grafting of bioactive epitopes into cyclotide scaffolds produces GPCR ligands with improved oral activity, enzymatic stability, and selectivity compared to linear peptide counterparts.","whyItMatters":"Peptide drugs typically cannot be taken orally and degrade quickly. Cyclotide scaffolds solve both problems, potentially enabling a new generation of oral peptide medicines targeting the largest class of drug targets.","specificNumbers":"GPCRs: ~34% of approved drug targets; cyclotides: cyclic cystine knot, 3 disulfide bonds; some show oral activity in vivo","methodology":"Review of molecular grafting approaches using cyclotide scaffolds to engineer novel GPCR-targeting peptide ligands, with examples of improved pharmacokinetics.","limitations":"Review — most examples are preclinical; oral bioavailability improvements vary by construct; manufacturing scalability of cyclotide-based drugs not fully addressed."},{"rthcId":"RPEP-05018","title":"Efficacy and safety of cerebrolysin in neurorecovery after moderate-severe traumatic brain injury: results from the CAPTAIN II trial.","authors":"Muresanu, Dafin F; Florian, Stefan; Hömberg, Volker; Matula, Christian; von Steinbüchel, Nicole; Vos, Pieter E; von Wild, Klaus; Birle, Codruta; Muresanu, Ioana; Slavoaca, Dana; Rosu, Olivia Verisezan; Strilciuc, Stefan; Vester, Johannes","year":2020,"journal":"Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 41(5), 1171-1181","doi":"10.1007/s10072-019-04181-y","pmid":"31897941","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05019","title":"Neurokinin receptor antagonism: a patent review (2014-present).","authors":"Muñoz, Miguel; Coveñas, Rafael","year":2020,"journal":"Expert opinion on therapeutic patents, 30(7), 527-539","doi":"10.1080/13543776.2020.1769599","pmid":"32401556","tags":["neuropeptides","cancer","pain","regulatory"],"studyType":"review","evidenceStrength":"low","keyFinding":"Only 5 NK-1R antagonists are clinically approved (all for emesis) despite the tachykinin system's involvement in cancer, pain, itch, obesity, and numerous other conditions — representing significant therapeutic underexploration.","whyItMatters":"Blocking neuropeptide signaling through NK receptors could treat conditions from cancer to chronic itch, but these drugs remain almost exclusively used for nausea — a missed therapeutic opportunity.","specificNumbers":"5 approved NK-1R antagonists; 0 NK-2R/NK-3R approved; patents cover: cancer, pruritus, cardiomyopathy, respiratory, infection, eye, weight, fear, hot flashes, reproduction","methodology":"Patent review covering NK receptor antagonist inventions and clinical applications from 2014 to 2020.","limitations":"Patent review format — focuses on inventions rather than clinical evidence strength; many proposed applications remain preclinical; reasons for limited clinical translation not fully analyzed."},{"rthcId":"RPEP-05020","title":"Sex Differences in the Neuropeptide Y System and Implications for Stress Related Disorders.","authors":"Nahvi, Roxanna J; Sabban, Esther L","year":2020,"journal":"Biomolecules, 10(9)","doi":"10.3390/biom10091248","pmid":"32867327","tags":["neuropeptides","anxiety-mood","nasal-peptides"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Females have lower baseline NPY expression in multiple brain regions than males, with sex-dependent differences in NPY's anxiolytic and antidepressant effects and stress-responsive expression patterns.","whyItMatters":"Most NPY research uses only males despite women's doubled vulnerability to PTSD and depression. Understanding sex differences in NPY is critical for developing effective intranasal NPY therapies for both sexes.","specificNumbers":"Women 2x risk for PTSD, depression, anxiety; lower baseline NPY in most brain regions; NPY KO: depression both sexes, anxiety more in males","methodology":"Narrative review synthesizing preclinical and genetic model studies on sex differences in the NPY system under basal and stressed conditions.","limitations":"Mostly animal studies; human sex difference data limited; hormonal cycle effects on NPY not fully characterized; review highlights gaps rather than providing definitive mechanisms."},{"rthcId":"RPEP-05021","title":"Expression and Localization of Paneth Cells and Their α-Defensins in the Small Intestine of Adult Mouse.","authors":"Nakamura, Kiminori; Yokoi, Yuki; Fukaya, Rie; Ohira, Shuya; Shinozaki, Ryuga; Nishida, Takuto; Kikuchi, Mani; Ayabe, Tokiyoshi","year":2020,"journal":"Frontiers in immunology, 11, 570296","doi":"10.3389/fimmu.2020.570296","pmid":"33154750","tags":["antimicrobial-peptides","gut-healing","immune-function"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"Alpha-defensin (cryptdin) expression increases 4-50 fold from duodenum to ileum, with corresponding increases in Paneth cell density and bactericidal activity, regulated by microbial presence.","whyItMatters":"Understanding where and how the gut produces antimicrobial peptides is fundamental to gut health — this topographic map reveals that the ileum is the primary defensin defense zone.","specificNumbers":"Crp mRNA 5x10^3 to 1x10^6 copies/5ng RNA; ileum 4-50x higher; 3-7x more Paneth cells/crypt in ileum; germ-free: reduced expression and killing","methodology":"Mouse study using isolated intestinal crypts from duodenum, jejunum, and ileum to measure defensin mRNA (qPCR), immunohistochemistry, and bactericidal assays, compared with germ-free mice.","limitations":"Mouse model (ICR strain) — human Paneth cell distribution differs; single time point; germ-free comparison provides correlation but not causation for microbial regulation."},{"rthcId":"RPEP-05022","title":"Continuous infusion of substance P inhibits acute, but not subacute, inflammatory pain induced by complete Freund's adjuvant.","authors":"Nakamura, Yoki; Fukushige, Ryo; Watanabe, Kohei; Kishida, Yuki; Hisaoka-Nakashima, Kazue; Nakata, Yoshihiro; Morioka, Norimitsu","year":2020,"journal":"Biochemical and biophysical research communications, 533(4), 971-975","doi":"10.1016/j.bbrc.2020.09.113","pmid":"33008602","tags":["neuropeptides","pain"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"Striatal substance P via NK1 receptors provides antinociception in acute (3-day) but not subacute (7-day) inflammatory pain, due to inflammation-induced NK1 receptor downregulation.","whyItMatters":"Understanding when neuropeptide pain pathways work — and when they stop working — is critical for developing effective pain treatments and understanding why chronic pain becomes treatment-resistant.","specificNumbers":"Day 3: SP reduced allodynia (NK1R-dependent); Day 7: SP ineffective; NK1R protein decreased at day 7; paw edema unaffected","methodology":"Animal study using reverse microdialysis to continuously infuse substance P into rat dorsal striatum, measuring mechanical allodynia and paw edema at 3 and 7 days after CFA-induced inflammation, with NK1 receptor protein quantification.","limitations":"Rat model with direct brain infusion — not a practical delivery route; single inflammatory model (CFA); mechanism of NK1 downregulation not fully characterized."},{"rthcId":"RPEP-05023","title":"Continuous infusion of substance P into rat striatum relieves mechanical hypersensitivity caused by a partial sciatic nerve ligation via activation of striatal muscarinic receptors.","authors":"Nakamura, Yoki; Fukushige, Ryo; Watanabe, Kohei; Kishida, Yuki; Hisaoka-Nakashima, Kazue; Nakata, Yoshihiro; Morioka, Norimitsu","year":2020,"journal":"Behavioural brain research, 391, 112714","doi":"10.1016/j.bbr.2020.112714","pmid":"32461131","tags":["neuropeptides","pain"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"Continuous striatal substance P infusion dose-dependently relieved neuropathic pain via NK1 receptors activating muscarinic cholinergic neurons — a novel brain-based analgesic pathway.","whyItMatters":"Neuropathic pain is notoriously difficult to treat. This study identifies a new brain circuit — striatal substance P activating cholinergic neurons — that could be targeted for chronic pain management.","specificNumbers":"SP dose-dependent at 0.2-0.8 ug/mL; NK1R-dependent (CP96345); muscarinic-dependent (atropine); nicotinic-independent (mecamylamine); acute/ipsilateral ineffective","methodology":"Animal study using reverse microdialysis to deliver continuous substance P into rat striatum after partial sciatic nerve ligation, with pharmacological dissection using NK1 antagonist, atropine, and mecamylamine.","limitations":"Invasive brain infusion delivery — not clinically practical as-is; rat model; only mechanical hypersensitivity tested; acute injection was ineffective, requiring continuous administration."},{"rthcId":"RPEP-05024","title":"Augmented osteogenesis of mesenchymal stem cells using a fragmented Runx2 mixed with cell-penetrating, dimeric a-helical peptide.","authors":"Nam, So Hee; Lee, Yan; Ahn, Joon Hyung; Chung, Chun Kee; Yang, Hee-Jin; Park, Sung Bae; Jang, Sangmok","year":2020,"journal":"European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 144, 105210","doi":"10.1016/j.ejps.2019.105210","pmid":"31899341","tags":["cell-penetrating","bone-joint","peptide-delivery"],"studyType":"in-vitro","evidenceStrength":"low-moderate","keyFinding":"The cyclic cLK peptide delivered fragmented Runx2 into stem cells more efficiently than Tat-CPP, producing 1.2-fold greater mineralization and higher osteogenic gene expression.","whyItMatters":"Bone regeneration therapies need efficient ways to program stem cells. Delivering transcription factors via CPPs could guide bone formation without genetic manipulation, advancing regenerative medicine.","specificNumbers":"cLK enhanced fRunx2 penetration; 1.2x more alizarin red vs Tat; higher ALP and osteocalcin gene expression","methodology":"In-vitro study comparing cLK and Tat peptide delivery of fluorescently labeled fragmented Runx2 into MC3T3 cells and rat mesenchymal stem cells, measuring uptake, mineralization, and gene expression.","limitations":"In-vitro study only; 1.2-fold improvement is modest; no in-vivo bone formation testing; long-term effects and optimal dosing not established."},{"rthcId":"RPEP-05025","title":"Precision medicine in distinct heart failure phenotypes: Focus on clinical epigenetics.","authors":"Napoli, Claudio; Benincasa, Giuditta; Donatelli, Francesco; Ambrosio, Giuseppe","year":2020,"journal":"American heart journal, 224, 113-128","doi":"10.1016/j.ahj.2020.03.007","pmid":"32361531","tags":["natriuretic-peptides","cardiovascular"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Hypomethylation at the H3K9 promoter of ANP and BNP genes reactivates fetal gene expression in failing hearts, while broader epigenetic changes drive metabolic and structural maladaptation.","whyItMatters":"Understanding why BNP and ANP rise in heart failure at the epigenetic level could enable precision medicine — matching patients to therapies based on their molecular profile rather than one-size-fits-all treatment.","specificNumbers":"ANP/BNP H3K9 promoter hypomethylation; KLF15 hypermethylation; miR-10a/155/31/92 prognostic; therapeutics: hydralazine, statins, apabetalone, omega-3","methodology":"Narrative review mapping epigenetic mechanisms (DNA methylation, histone modifications, miRNAs) in heart failure pathogenesis, with proposed clinical research strategy (EPIKO-STORM).","limitations":"Review with proposed framework (EPIKO-STORM) that has not been clinically validated; epigenetic therapies for heart failure remain largely in trials; causal relationships not fully established."},{"rthcId":"RPEP-05026","title":"Antisense peptide nucleic acids againstftsZ andefaA genes inhibit growth and biofilm formation of Enterococcusfaecalis.","authors":"Narenji, Hanar; Teymournejad, Omid; Rezaee, Mohammad Ahangarzadeh; Taghizadeh, Sepehr; Mehramuz, Bahareh; Aghazadeh, Mohammad; Asgharzadeh, Mohammad; Madhi, Masoumeh; Gholizadeh, Pourya; Ganbarov, Khudaverdi; Yousefi, Mehdi; Pakravan, Asrin; Dal, Tuba; Ahmadi, Raman; Samadi Kafil, Hossein","year":2020,"journal":"Microbial pathogenesis, 139, 103907","doi":"10.1016/j.micpath.2019.103907","pmid":"31811888","tags":["cell-penetrating","antimicrobial-peptides","infection","peptide-delivery"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Anti-ftsZ PNAs completely inhibited E. faecalis growth, while CPP-conjugated anti-efaA PNAs reduced efaA gene expression and biofilm formation by 95%, with no mammalian cell toxicity.","whyItMatters":"Antibiotic-resistant Enterococcus is a growing hospital threat. Gene-targeted PNA approaches could provide precision antimicrobials that bypass conventional resistance mechanisms.","specificNumbers":"Anti-ftsZ: eliminated growth; anti-efaA: 95% reduction in expression and biofilm; no MCF7 toxicity","methodology":"In-vitro study using antisense PNAs targeting ftsZ and efaA genes in E. faecalis ATCC 29212, with electroporation and CPP delivery, measuring growth inhibition, biofilm formation, gene expression, and cytotoxicity.","limitations":"In-vitro study with a single bacterial strain; electroporation is not clinically viable for ftsZ delivery; CPP-PNA delivery needs in-vivo testing; manufacturing scalability not addressed."},{"rthcId":"RPEP-05027","title":"Tachykinin signaling in the control of puberty onset.","authors":"Navarro, Víctor M","year":2020,"journal":"Current opinion in endocrine and metabolic research, 14, 92-96","doi":"10.1016/j.coemr.2020.06.009","pmid":"32832725","tags":["neuropeptides","fertility","receptor-signaling"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Tachykinins (NKB, NKA, substance P) initiate puberty by stimulating kisspeptin neuron activation in the hypothalamus, with loss of tachykinin signaling causing delayed/absent puberty in humans and mice.","whyItMatters":"Understanding the neuropeptide triggers of puberty is essential for diagnosing and treating disorders of pubertal timing, including precocious puberty and delayed sexual maturation.","specificNumbers":"NKB primary; tachykinin expression increases pre-puberty; KO: delayed/absent puberty; chronic activation: advanced puberty","methodology":"Narrative review of human genetic studies, animal knockout models, and pharmacological studies examining tachykinin roles in pubertal development.","limitations":"Review based largely on animal models; human data mainly from rare genetic conditions; exact mechanisms of tachykinin timing signals remain incompletely understood."},{"rthcId":"RPEP-05028","title":"Cell Penetrating Peptides Used in Delivery of Therapeutic Oligonucleotides Targeting Hepatitis B Virus.","authors":"Ndeboko, Bénédicte; Omouessi, Serge Thierry; Ongali, Brice; Mouinga-Ondémé, Augustin","year":2020,"journal":"Pharmaceuticals (Basel, Switzerland), 13(12)","doi":"10.3390/ph13120483","pmid":"33371278","tags":["cell-penetrating","infection","peptide-delivery"],"studyType":"review","evidenceStrength":"low-moderate","keyFinding":"CPP-conjugated PNAs and siRNAs can inhibit hepatitis B virus replication and antigen expression, with CPPs solving the critical intracellular delivery challenge for oligonucleotide-based antivirals.","whyItMatters":"Chronic hepatitis B affects ~300 million people with no cure. CPP-delivered gene-silencing therapies could offer a functional cure by targeting viral genes that current drugs cannot reach.","specificNumbers":"PNAs reduced hepadnaviral replication; siRNAs inhibited HBV antigens; CPP conjugation improves delivery","methodology":"Review of PNA and siRNA anti-HBV approaches, including original data on PNA-mediated inhibition in duck HBV model and discussion of CPP delivery strategies.","limitations":"Largely preclinical with duck HBV model and cell culture; in-vivo human liver delivery remains challenging; CPP-oligonucleotide stability and toxicity need further assessment."},{"rthcId":"RPEP-05029","title":"Amygdala, neuropeptides, and chronic pain-related affective behaviors.","authors":"Neugebauer, Volker; Mazzitelli, Mariacristina; Cragg, Bryce; Ji, Guangchen; Navratilova, Edita; Porreca, Frank","year":2020,"journal":"Neuropharmacology, 170, 108052","doi":"10.1016/j.neuropharm.2020.108052","pmid":"32188569","tags":["neuropeptides","pain","oxytocin","opioid-peptides"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"The amygdala contains a rich neuropeptide network where CGRP, CRF, oxytocin, vasopressin, opioids, neuropeptide S, and somatostatin interact to modulate pain processing and emotional-affective pain behaviors.","whyItMatters":"Chronic pain is as much emotional as physical. Understanding how amygdala neuropeptides modulate pain-related distress opens targets for treating the suffering — not just the sensation — of chronic pain.","specificNumbers":"Neuropeptides: CGRP, CRF, SOM, NPS, OXT, AVP, endorphin, enkephalin, dynorphin; nuclei: BLA, CeA, ITC","methodology":"Narrative review of neuropeptide signaling in amygdala nuclei (BLA, CeA, ITC) and their roles in pain modulation, synthesizing electrophysiology, behavioral, and anatomical studies.","limitations":"Review based primarily on animal studies; translation to human chronic pain conditions requires caution; interactions between multiple neuropeptide systems are incompletely understood."},{"rthcId":"RPEP-05030","title":"In Vitro Selection of Peptides and Proteins-Advantages of mRNA Display.","authors":"Newton, Matilda S; Cabezas-Perusse, Yari; Tong, Cher Ling; Seelig, Burckhard","year":2020,"journal":"ACS synthetic biology, 9(2), 181-190","doi":"10.1021/acssynbio.9b00419","pmid":"31891492","tags":["drug-discovery","peptide-engineering"],"studyType":"review","evidenceStrength":"n/a-review","keyFinding":"mRNA display is a powerful laboratory technique that allows researchers to screen trillions of peptide and protein variants simultaneously to find ones with desired functions. The technique works by physically linking each protein to the mRNA molecule that encodes it, creating a searchable library where every candidate comes with its own genetic barcode.\n\nThe review argues that mRNA display has key advantages over competing methods like phage display, cell-surface display, and ribosomal display — primarily the stability of the protein-mRNA link and the greater experimental control it offers researchers.","whyItMatters":"Finding the right peptide drug candidate from billions of possibilities is like finding a needle in a haystack. mRNA display dramatically accelerates this process by letting scientists test trillions of candidates at once. This review explains why the technique has become a go-to method for peptide drug discovery and protein engineering, making it foundational reading for understanding how modern peptide therapeutics are discovered.","specificNumbers":"Library size: trillions of variants · Compared methods: cell-surface display, phage display, ribosomal display, mRNA display","methodology":"This is a review article that compares mRNA display to other in vitro and in vivo selection methods, describing the technical advantages and innovative applications in directed evolution, protein engineering, and drug discovery.","limitations":"As a review, this paper doesn't present new experimental data. It focuses on advantages of mRNA display and may understate limitations or areas where competing methods perform better. Published in 2020, it may not cover the most recent advances in the field."},{"rthcId":"RPEP-05031","title":"Role of Antimicrobial Peptides in Skin Barrier Repair in Individuals with Atopic Dermatitis.","authors":"Nguyen, Hai Le Thanh; Trujillo-Paez, Juan Valentin; Umehara, Yoshie; Yue, Hainan; Peng, Ge; Kiatsurayanon, Chanisa; Chieosilapatham, Panjit; Song, Pu; Okumura, Ko; Ogawa, Hideoki; Ikeda, Shigaku; Niyonsaba, François","year":2020,"journal":"International journal of molecular sciences, 21(20)","doi":"10.3390/ijms21207607","pmid":"33066696","tags":["ll-37","antimicrobial-peptides","skin-repair","immune-function"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Antimicrobial peptides LL-37, human beta-defensins, and S100A7 improve tight junction barrier function in addition to their antimicrobial activity, suggesting they could be used for barrier repair in atopic dermatitis.","whyItMatters":"Atopic dermatitis affects up to 20% of children and 3% of adults. AMPs that both fight infection and repair the skin barrier could provide a new treatment paradigm beyond steroids and immunosuppressants.","specificNumbers":"AMPs: LL-37, hBDs, S100A7; barrier: stratum corneum + tight junctions; AMPs improve TJ function","methodology":"Narrative review analyzing the relationship between skin barrier disruption, antimicrobial peptide expression, and tight junction function in atopic dermatitis.","limitations":"Review without new experimental data; AMP-tight junction mechanisms not fully characterized; clinical trials of AMP-based barrier repair therapies are still needed."},{"rthcId":"RPEP-05032","title":"Short-term intestinal lipase inhibition in normal-weight individuals does not affect postprandial peptide YY3-36 and glucagon-like peptide-1 levels, hunger or satiety.","authors":"Nguyen, Nga N; Kolobova, Irina; Wolfe, Bruce M; Purnell, Jonathan Q","year":2020,"journal":"Diabetes, obesity & metabolism, 22(12), 2499-2503","doi":"10.1111/dom.14182","pmid":"32869451","tags":["glp-1","weight-loss"],"studyType":"rct","evidenceStrength":"low","keyFinding":"Short-term orlistat-induced fat malabsorption did not increase postprandial GLP-1 or PYY3-36 levels or affect hunger/satiety in normal-weight individuals.","whyItMatters":"Understanding which mechanisms drive beneficial hormone changes after bariatric surgery could help develop non-surgical treatments for obesity using similar pathways.","specificNumbers":"5 participants; orlistat 120 mg x 3 days; no change in GLP-1, PYY3-36, hunger, satiety; increased peak glucose and insulin","methodology":"Randomized, double-blinded, crossover trial with 5 healthy participants receiving orlistat 120mg or placebo for 3 days, with 14-hour meal test measuring hormones and appetite.","limitations":"Very small sample (n=5); short-term (3 days); normal-weight participants — obese individuals may respond differently; orlistat does not perfectly replicate bypass-type malabsorption."},{"rthcId":"RPEP-05033","title":"Oxyntomodulin and Glicentin May Predict the Effect of Bariatric Surgery on Food Preferences and Weight Loss.","authors":"Nielsen, Mette S; Ritz, Christian; Wewer Albrechtsen, Nicolai J; Holst, Jens Juul; le Roux, Carel W; Sjödin, Anders","year":2020,"journal":"The Journal of clinical endocrinology and metabolism, 105(4)","doi":"10.1210/clinem/dgaa061","pmid":"32016415","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Enhanced postprandial responses of glicentin and oxyntomodulin after surgery predicted greater weight loss at 18 months (both P < .01) and were associated with decreased preference for energy-dense foods (P ≤ .04). Notably, GLP-1, PYY, and ghrelin changes were not individually associated with weight loss.\n\nPostprandial hormone responses differed significantly between Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) for glicentin, oxyntomodulin, GLP-1, and ghrelin (all P ≤ .02). When combining all five hormones in a model, they explained 60% of weight loss variation, 19% of energy intake variation, and 33% of energy density preference variation.","whyItMatters":"Bariatric surgery doesn't work equally well for everyone, and doctors currently can't predict who will have the best outcomes. If oxyntomodulin and glicentin levels measured after surgery can identify patients who may struggle with weight loss, clinicians could provide earlier, more targeted support. These findings also shift attention from GLP-1 — the most-studied gut hormone — to two related but underappreciated peptides.","specificNumbers":"","methodology":"This was a prospective study of 42 adults with severe obesity (32 RYGB, 10 SG). Postprandial responses of five gastrointestinal peptides — glicentin, oxyntomodulin, GLP-1, PYY, and ghrelin — were measured before and 6 months after surgery using meal tests. Food preferences and energy intake were assessed using a buffet meal test at both timepoints. Weight loss was measured at 18 months post-surgery.","limitations":"The sample size was small (42 patients) with an unbalanced design (32 RYGB vs 10 SG), limiting the power to compare surgery types. The study was observational, so it cannot prove causation between hormone changes and weight loss. The 18-month follow-up may not capture long-term weight trajectory. The authors note these findings need replication."},{"rthcId":"RPEP-05034","title":"Immunoinformatics: Predicting Peptide-MHC Binding.","authors":"Nielsen, Morten; Andreatta, Massimo; Peters, Bjoern; Buus, Søren","year":2020,"journal":"Annual review of biomedical data science, 3, 191-215","doi":"10.1146/annurev-biodatasci-021920-100259","pmid":"37427310","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05035","title":"Effects of recombinant human brain natriuretic peptide in patients with acute myocardial infarction undergoing percutaneous coronary intervention: A systematic review and meta-analysis.","authors":"Ning, Cheng; Zheng, Yawei; Li, Jie; Liu, Ming; Fang, Zhuyuan","year":2020,"journal":"Medicine, 99(11), e19479","doi":"10.1097/MD.0000000000019479","pmid":"32176080","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05036","title":"Mixed 20-peptide cancer vaccine in combination with docetaxel and dexamethasone for castration-resistant prostate cancer: a randomized phase II trial.","authors":"Noguchi, Masanori; Arai, Gaku; Egawa, Shin; Ohyama, Chikara; Naito, Seiji; Matsumoto, Kazumasa; Uemura, Hirotsugu; Nakagawa, Masayuki; Nasu, Yasutomo; Eto, Masatoshi; Suekane, Shigetaka; Sasada, Tetsuro; Shichijo, Shigeki; Yamada, Akira; Kakuma, Tatsuyuki; Itoh, Kyogo","year":2020,"journal":"Cancer immunology, immunotherapy : CII, 69(5), 847-857","doi":"10.1007/s00262-020-02498-8","pmid":"32025848","tags":["cancer","immune-function","clinical-trials"],"studyType":"rct","evidenceStrength":"moderate","keyFinding":"KRM-20 vaccine elicited significant peptide-specific CTL and IgG immune responses (p=0.007, p=0.018) but did not improve clinical outcomes versus placebo when combined with docetaxel in CRPC.","whyItMatters":"Peptide cancer vaccines consistently generate immune responses but often fail to improve survival — understanding why is essential for improving immunotherapy for prostate and other cancers.","specificNumbers":"25 vs 26 patients; PSA >50% decline: 56.5% vs 53.8% (NS); IgG p=0.018; CTL p=0.007; no PFS/OS difference; subgroup: benefit if lymphocytes >=26% or PSA <11.2","methodology":"Double-blind, placebo-controlled, randomized phase II trial across 10 centers in Japan with 51 chemotherapy-naive CRPC patients receiving KRM-20 or placebo plus docetaxel/dexamethasone.","limitations":"Small sample (n=51); phase II without OS primary endpoint; HLA restriction limits applicability; subgroup analyses are hypothesis-generating only; short follow-up."},{"rthcId":"RPEP-05037","title":"Intratracheal GLP-1 receptor agonist treatment up-regulates mucin via p38 and exacerbates emphysematous phenotype in mucus hypersecretory obstructive lung diseases.","authors":"Nohara, Hirofumi; Nakashima, Ryunosuke; Kamei, Shunsuke; Fujikawa, Haruka; Ueno-Shuto, Keiko; Kawakami, Taisei; Eto, Yuka; Suico, Mary Ann; Li, Jian-Dong; Kai, Hirofumi; Shuto, Tsuyoshi","year":2020,"journal":"Biochemical and biophysical research communications, 524(2), 332-339","doi":"10.1016/j.bbrc.2020.01.081","pmid":"31996306","tags":["glp-1","exenatide","liraglutide","respiratory","side-effects"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"GLP-1 receptor agonists upregulate mucin expression in airways via p38 MAPK, exacerbating emphysematous phenotypes in obstructive lung disease models.","whyItMatters":"Millions of people use GLP-1 drugs for diabetes and obesity. If these drugs worsen lung disease, patients with concurrent COPD or asthma need careful monitoring — especially as inhaled GLP-1 delivery is explored.","specificNumbers":"Exendin-4 and liraglutide upregulated mucin; p38 MAPK activation; worsened emphysema in obstructive model; GLP-1R highly expressed in lung","methodology":"Combined in-vitro (airway epithelial cells) and in-vivo (mouse) studies testing exendin-4 and liraglutide effects on mucin expression and pulmonary pathology under normal and obstructive conditions.","limitations":"Mouse and cell culture models — human relevance not confirmed; intratracheal delivery may produce higher local concentrations than systemic administration; short-term study."},{"rthcId":"RPEP-05038","title":"Major cardiovascular events, heart failure, and atrial fibrillation in patients treated with glucagon-like peptide-1 receptor agonists: An updated meta-analysis of randomized controlled trials.","authors":"Nreu, Besmir; Dicembrini, Ilaria; Tinti, Federico; Sesti, Giorgio; Mannucci, Edoardo; Monami, Matteo","year":2020,"journal":"Nutrition, metabolism, and cardiovascular diseases : NMCD, 30(7), 1106-1114","doi":"10.1016/j.numecd.2020.03.013","pmid":"32448716","tags":["glp-1","cardiovascular","diabetes","clinical-trials"],"studyType":"meta-analysis","evidenceStrength":"high","keyFinding":"GLP-1 RAs significantly reduced MACE (OR 0.87), all-cause mortality (OR 0.89), and showed a trend toward heart failure reduction (OR 0.93) without increasing atrial fibrillation risk across 43 trials.","whyItMatters":"This provides the strongest evidence base for GLP-1 drugs as cardiovascular protectants — not just glucose-lowering agents — supporting their use as first-line therapy for diabetic patients at cardiovascular risk.","specificNumbers":"MACE OR 0.87 (0.83-0.92); all-cause mortality OR 0.89 (0.83-0.96); stroke reduced; HF OR 0.93 (NS); AF OR 0.94 (no increase)","methodology":"Systematic review and meta-analysis of 43 randomized controlled trials ≥52 weeks enrolling 63,134 type 2 diabetes patients comparing GLP-1 RAs versus placebo or non-GLP-1 RA drugs.","limitations":"Pooled analysis across different GLP-1 RAs may mask drug-specific differences; heart failure reduction did not reach statistical significance; trial populations predominantly type 2 diabetes with high cardiovascular risk."},{"rthcId":"RPEP-05039","title":"Characterization and Antioxidant Activity of Collagen, Gelatin, and the Derived Peptides from Yellowfin Tuna (Thunnus albacares) Skin.","authors":"Nurilmala, Mala; Hizbullah, Hanifah Husein; Karnia, Euis; Kusumaningtyas, Eni; Ochiai, Yoshihiro","year":2020,"journal":"Marine drugs, 18(2)","doi":"10.3390/md18020098","pmid":"32023998","tags":["collagen-peptides","bioactive-food-peptides"],"studyType":"in-vitro","evidenceStrength":"low","keyFinding":"Enzymatic hydrolysis of tuna skin collagen (52.7% degree of hydrolysis) and gelatin (45.2%) produced peptide fractions with significantly enhanced antioxidant activity across multiple molecular weight ranges.","whyItMatters":"Fish processing generates massive skin waste. Converting it to antioxidant collagen peptides creates value from waste while producing ingredients for functional foods and nutraceuticals.","specificNumbers":"Collagen yield 22.6%; gelatin 20%; DH 52.7%/45.2%; collagen peptides 2.94-11.93 kDa; best antioxidant: <3, 3-10, 10-30 kDa fractions","methodology":"In-vitro study extracting collagen (acetic acid) and gelatin (citric acid) from tuna skin, followed by Alcalase hydrolysis, molecular weight fractionation, and antioxidant activity measurement.","limitations":"In-vitro antioxidant assays only; no in-vivo or human data; specific peptide sequences not identified; bioavailability after oral consumption not tested."},{"rthcId":"RPEP-05040","title":"Defensins of Grasses: A Systematic Review.","authors":"Odintsova, Tatyana I; Slezina, Marina P; Istomina, Ekaterina A","year":2020,"journal":"Biomolecules, 10(7)","doi":"10.3390/biom10071029","pmid":"32664422","tags":["antimicrobial-peptides","peptide-design"],"studyType":"systematic-review","evidenceStrength":"moderate","keyFinding":"Grass defensins represent a large but undercharacterized family of plant antimicrobial peptides, with genome mining revealing numerous novel defensin-like sequences across all grass species examined.","whyItMatters":"Grass defensins could provide templates for new antimicrobial drugs and crop protection agents, addressing both antibiotic resistance and agricultural disease challenges.","specificNumbers":"Poaceae is one of the largest flowering plant families; wheat/barley γ-thionins were the first plant defensins isolated","methodology":"Systematic review of characterized grass defensins combined with in-silico genome mining for defensin-like sequences across all described grass species.","limitations":"Most grass defensins remain functionally uncharacterized; in-silico predictions need experimental validation; structure-function relationships are incomplete for most species."},{"rthcId":"RPEP-05041","title":"Reduced induction of human β-defensins is involved in the pathological mechanism of cutaneous adverse effects caused by epidermal growth factor receptor monoclonal antibodies.","authors":"Ommori, R; Nakamura, Y; Miyagawa, F; Shobatake, C; Ogawa, K; Koyama, F; Sho, M; Ota, I; Kitahara, T; Hontsu, S; Muro, S; Asada, H","year":2020,"journal":"Clinical and experimental dermatology, 45(8), 1055-1058","doi":"10.1111/ced.14311","pmid":"32460367","tags":["antimicrobial-peptides","skin-repair","immune-function","cancer"],"studyType":"observational","evidenceStrength":"preliminary","keyFinding":"Patients developing papulopustular eruptions from EGFR monoclonal antibodies showed significant reductions in skin hBD1 and hBD3 levels, linking antimicrobial peptide suppression to drug-induced skin toxicity.","whyItMatters":"Skin rashes affect up to 80% of patients on EGFR inhibitors and can lead to dose reductions or discontinuation. Understanding the defensin mechanism could enable preventive treatments.","specificNumbers":"Significant decrease in hBD1 and hBD3; non-significant decrease in hBD2 in patients with eruptions","methodology":"Observational study measuring human beta-defensin levels (hBD1, hBD2, hBD3) in stratum corneum samples before and after EGFR monoclonal antibody therapy, comparing patients with and without eruptions.","limitations":"Small sample size not specified; observational design cannot prove causation; only stratum corneum defensins measured; other innate immune factors not assessed."},{"rthcId":"RPEP-05042","title":"Enhanced osteogenesis of human mesenchymal stem cells by self-assembled peptide hydrogel functionalized with glutamic acid templated peptides.","authors":"Onak, Günnur; Gökmen, Oğuzhan; Yaralı, Ziyşan Buse; Karaman, Ozan","year":2020,"journal":"Journal of tissue engineering and regenerative medicine, 14(9), 1236-1249","doi":"10.1002/term.3095","pmid":"32615018","tags":["peptide-delivery","bone-joint","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Glutamic acid-templated peptide motifs (EEGGC and EEEEE) conjugated to KLD self-assembling scaffolds significantly enhanced osteogenic differentiation markers and calcium deposition in human MSCs.","whyItMatters":"Bone defects are common clinical problems. Injectable peptide hydrogels that actively promote bone formation could provide minimally invasive alternatives to bone grafts.","specificNumbers":"3 gel concentrations (0.5%, 1%, 2%); significant increases in ALP, COL-1, osteopontin, osteocalcin expression","methodology":"In-vitro study designing KLD-O1 and KLD-O2 peptide hydrogels at three concentrations, characterizing structure (AFM, SEM), rheology, and measuring osteogenic markers (ALP, COL-1, OP, OCN) in human MSCs.","limitations":"In-vitro study only; no animal bone defect model testing; long-term scaffold degradation and bone integration not assessed; mechanical strength for load-bearing applications unclear."},{"rthcId":"RPEP-05043","title":"Targeting NF-κB by the Cell-Permeable NEMO-Binding Domain Peptide Improves Albuminuria and Renal Lesions in an Experimental Model of Type 2 Diabetic Nephropathy.","authors":"Opazo-Ríos, Lucas; Plaza, Anita; Sánchez Matus, Yenniffer; Bernal, Susana; Lopez-Sanz, Laura; Jimenez-Castilla, Luna; Carpio, Daniel; Droguett, Alejandra; Mezzano, Sergio; Egido, Jesús; Gomez-Guerrero, Carmen","year":2020,"journal":"International journal of molecular sciences, 21(12)","doi":"10.3390/ijms21124225","pmid":"32545818","tags":["cell-penetrating","kidney","diabetes","inflammation"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Active NBD peptide reduced albuminuria by >40%, decreased podocyte loss and basement membrane thickness, and modulated inflammatory markers in a type 2 diabetic nephropathy mouse model.","whyItMatters":"Diabetic kidney disease is the leading cause of kidney failure worldwide. A peptide that blocks the central inflammatory pathway driving kidney damage could offer a targeted therapy beyond blood sugar control.","specificNumbers":">40% average reduction in albuminuria; doses of 10 and 6 mcg/g body weight; first nephroprotective NBD study in T2D model","methodology":"Animal study using obese diabetic mice randomized to active NBD peptide (two doses), inactive mutant peptide, or vehicle, with in-vivo imaging, kidney histology, and in-vitro mesangial cell NF-κB assays.","limitations":"Mouse model; sample size not clearly specified; preliminary evidence; peptide stability and delivery optimization needed for clinical translation; long-term effects not assessed."},{"rthcId":"RPEP-05044","title":"A new class of PentixaFor- and PentixaTher-based theranostic agents with enhanced CXCR4-targeting efficiency.","authors":"Osl, Theresa; Schmidt, Alexander; Schwaiger, Markus; Schottelius, Margret; Wester, Hans-Jürgen","year":2020,"journal":"Theranostics, 10(18), 8264-8280","doi":"10.7150/thno.45537","pmid":"32724470","tags":["cyclic-peptides","cancer","peptide-design"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Modified linker cyclic peptides achieved 10-fold enhanced CXCR4 affinity, with [177Lu]DOTA-r-a-ABA-CPCR4 showing superior tumor uptake (18.3 vs 12.4 %iD/g) and 2-4x better tumor/organ ratios at 48h.","whyItMatters":"CXCR4-targeted radioligand therapy is entering clinical use for blood cancers. More potent and selective peptide ligands with better tumor retention could significantly improve treatment outcomes.","specificNumbers":"10x improved hCXCR4 affinity; 4x higher cell uptake; tumor uptake 18.3 and 17.2 vs 12.4 %iD/g; 2-4x higher tumor/organ ratios at 48h","methodology":"Structure-activity study synthesizing novel CPCR4 analogs with modified linkers, evaluated via in-vitro affinity/internalization assays, small-animal PET imaging, and biodistribution in Daudi lymphoma xenograft mice.","limitations":"Mouse xenograft model; kidney accumulation remains an issue; PET imaging did not show advantage despite in-vitro improvements; clinical translation requires human dosimetry studies."},{"rthcId":"RPEP-05045","title":"Thymosin β4 is essential for adherens junction stability and epidermal planar cell polarity.","authors":"Padmanabhan, Krishnanand; Grobe, Hanna; Cohen, Jonathan; Soffer, Arad; Mahly, Adnan; Adir, Orit; Zaidel-Bar, Ronen; Luxenburg, Chen","year":2020,"journal":"Development (Cambridge, England), 147(23)","doi":"10.1242/dev.193425","pmid":"33310787","tags":["thymosin-beta-4","skin-repair"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Thymosin beta-4 depletion disrupted epidermal adherens junction stability and planar cell polarity by altering perijunctional G/F-actin ratios, causing eyelid closure and hair follicle angling defects.","whyItMatters":"Understanding how Tβ4 organizes skin tissue architecture explains its wound healing properties at a fundamental level and reveals why it is effective in promoting tissue repair.","specificNumbers":"Increased G/F-actin ratio at junctions; no change in total actin or F-actin content; eyelid closure and hair follicle angling disrupted","methodology":"Animal study using Tmsb4x-depleted mouse embryos combined with in-vitro keratinocyte cultures, analyzing actin dynamics, adherens junction structure, and planar cell polarity.","limitations":"Embryonic mouse model — adult wound healing implications are inferred; complete Tβ4 depletion is more extreme than therapeutic supplementation; specific actin pool dynamics are complex."},{"rthcId":"RPEP-05046","title":"Acute and Repeated Intranasal Oxytocin Differentially Modulate Brain-wide Functional Connectivity.","authors":"Pagani, Marco; De Felice, Alessia; Montani, Caterina; Galbusera, Alberto; Papaleo, Francesco; Gozzi, Alessandro","year":2020,"journal":"Neuroscience, 445, 83-94","doi":"10.1016/j.neuroscience.2019.12.036","pmid":"31917352","tags":["oxytocin","neuropeptides","nasal-peptides"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Acute intranasal oxytocin focally enhanced limbic connectivity, while repeated 7-day dosing caused widespread brain connectivity reconfiguration with paradoxical reduction in social behavior.","whyItMatters":"Intranasal oxytocin is being tested for autism and social impairment. This study shows repeated dosing may have opposite effects to single doses, potentially explaining inconsistent clinical trial results.","specificNumbers":"1 acute dose vs 7 daily doses; acute boosted limbic connectivity; repeated caused widespread cortical-limbic coupling and reduced social behavior","methodology":"fMRI-based circuit mapping in adult mice comparing acute versus 7-day repeated intranasal oxytocin, with cerebral blood volume mapping, functional connectivity analysis, and social behavior testing.","limitations":"Mouse model — human brain connectivity may respond differently; 7-day protocol is short-term; dosing may not match clinical intranasal protocols; social behaviors measured may not fully capture human social cognition."},{"rthcId":"RPEP-05047","title":"Immunomodulatory Role of the Antimicrobial LL-37 Peptide in Autoimmune Diseases and Viral Infections.","authors":"Pahar, Bapi; Madonna, Stefania; Das, Arpita; Albanesi, Cristina; Girolomoni, Giampiero","year":2020,"journal":"Vaccines, 8(3)","doi":"10.3390/vaccines8030517","pmid":"32927756","tags":["ll-37","immune-function","inflammation","infection"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"LL-37 complexed to self-DNA acts as an autoantigen in psoriasis and lupus, activating interferon production by plasmacytoid dendritic cells, while also having dual antiviral and pro-inflammatory roles.","whyItMatters":"LL-37 is central to both antimicrobial defense and autoimmune disease. Understanding its dual roles is essential for developing therapies that preserve its protective functions while blocking its pathogenic activities.","specificNumbers":"LL-37 produced by neutrophils, monocytes, macrophages, epithelial cells; acts as autoantigen when complexed with self-DNA","methodology":"Narrative review of LL-37 immunomodulatory roles in autoimmune diseases (psoriasis, lupus) and viral infections.","limitations":"Review without new experimental data; LL-37 roles in different viral infections vary widely; therapeutic targeting strategies are largely conceptual."},{"rthcId":"RPEP-05048","title":"Hexokinase II-Derived Cell-Penetrating Peptide Mediates Delivery of MicroRNA Mimic for Cancer-Selective Cytotoxicity.","authors":"Palanikumar, L; Al-Hosani, Sumaya; Kalmouni, Mona; Saleh, Hadi Omar; Magzoub, Mazin","year":2020,"journal":"Biochemistry, 59(24), 2259-2273","doi":"10.1021/acs.biochem.0c00141","pmid":"32491855","tags":["cell-penetrating","cancer","peptide-delivery"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"PAS-pHK peptide delivers miR-126 selectively to cancer cells, targeting mitochondria to induce apoptosis synergistically while showing no toxicity to non-cancerous cells.","whyItMatters":"Selective cancer cell killing without harming normal cells is the holy grail of cancer therapy. This peptide-miRNA approach achieves selectivity by exploiting cancer-specific hexokinase II overexpression.","specificNumbers":"PAS-pHK from N-terminal 15 amino acids of HKII; miR-126 synergistically enhanced anti-cancer effects; no toxicity to MCF-10A or HEK-93","methodology":"In-vitro study designing a hexokinase II-derived CPP conjugated to miR-126 mimic, measuring cellular uptake, mitochondrial effects, ATP depletion, apoptosis, and selectivity in cancer vs. normal cell lines.","limitations":"In-vitro only with limited cell line testing; no in-vivo tumor model; peptide stability in blood and biodistribution unknown; manufacturing of peptide-miRNA conjugates at scale not addressed."},{"rthcId":"RPEP-05049","title":"Detection of tumor antigens and tumor-antigen specific T cells in NSCLC patients: Correlation of the quality of T cell responses with NSCLC subtype.","authors":"Palata, Ondrej; Podzimkova Hradilova, Nada; Mysiková, Dagmar; Kutna, Beata; Mrazkova, Hana; Lischke, Robert; Spisek, Radek; Adkins, Irena","year":2020,"journal":"Immunology letters, 219, 46-53","doi":"10.1016/j.imlet.2020.01.001","pmid":"31931024","tags":["cancer","immune-function"],"studyType":"observational","evidenceStrength":"preliminary","keyFinding":"Squamous cell lung cancer patients showed significantly weaker T cell responses to tumor peptide antigens than adenocarcinoma patients despite higher antigen expression, indicating subtype-specific immune suppression.","whyItMatters":"Understanding why different lung cancer subtypes respond differently to immune stimulation is critical for designing effective peptide-based cancer vaccines and immunotherapies.","specificNumbers":"12 TAAs tested; 6 cell lines; 52 primary tumors; 32 patients; 4 of 6 cell lines suitable; Phase I trial NCT02470468","methodology":"Observational study analyzing tumor antigen expression in 6 cell lines and 52 primary tumors, plus peptide-specific T cell stimulation assays in 32 NSCLC patient blood samples.","limitations":"Small patient cohort (n=32); in-vitro T cell stimulation may not reflect in-vivo immunity; mechanistic basis for SCC T cell dysfunction not explored; limited to 12 antigens."},{"rthcId":"RPEP-05050","title":"Native Chemical Ligation via N-Acylurea Thioester Surrogates Obtained by Fmoc Solid-Phase Peptide Synthesis.","authors":"Palà-Pujadas, Judith; Blanco-Canosa, Juan B","year":2020,"journal":"Methods in molecular biology (Clifton, N.J.), 2133, 141-161","doi":"10.1007/978-1-0716-0434-2_7","pmid":"32144666","tags":["peptide-design","cyclic-peptides","antimicrobial-peptides"],"studyType":"methodology","evidenceStrength":"not-applicable","keyFinding":"Nbz/MeNbz thioester surrogates enable Fmoc-SPPS compatible native chemical ligation, demonstrated by successful synthesis and cyclization of the heterodimeric antimicrobial defensin RTD-1.","whyItMatters":"Making complex cyclic and modified peptides accessible through standard Fmoc synthesis democratizes the production of therapeutic peptides, including antimicrobial defensins and post-translationally modified proteins.","specificNumbers":"RTD-1 heterodimeric cyclic defensin; Fmoc-SPPS with Nbz/MeNbz surrogates; NCL at neutral pH","methodology":"Methodology paper describing Fmoc solid-phase synthesis of Nbz peptide thioester surrogates, optimization of coupling conditions, and application to NCL-mediated cyclization and folding of RTD-1 defensin.","limitations":"Methodology paper — demonstrated on one target peptide (RTD-1); scalability and generalizability to larger proteins need further demonstration; requires specialized reagents."},{"rthcId":"RPEP-05051","title":"An antibody-drug conjugate targeting a GSTA glycosite-signature epitope of MUC1 expressed by non-small cell lung cancer.","authors":"Pan, Deng; Tang, Yubo; Tong, Jiao; Xie, Chengmei; Chen, Jiaxi; Feng, Chunchao; Hwu, Patrick; Huang, Wei; Zhou, Dapeng","year":2020,"journal":"Cancer medicine, 9(24), 9529-9540","doi":"10.1002/cam4.3554","pmid":"33084221","tags":["cancer","peptide-delivery"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"16A-MMAE ADC targeting the GSTA glycosite-specific neoantigen peptide of MUC1 showed IC50 of 0.2-49.4 nM against cancer cells and dose-dependent tumor inhibition in vivo at 1 mg/kg minimum effective dose.","whyItMatters":"MUC1 is overexpressed in many cancers. A glycosite-specific ADC approach could enable personalized cancer treatment based on each tumor's specific glycosylation pattern.","specificNumbers":"IC50 0.2-49.4 nM; minimum effective dose 1 mg/kg; no significant toxicity at 3 mg/kg","methodology":"Preclinical study with in-vitro ADC activity across cancer cell lines, in-vivo xenograft efficacy in NCI-H838 NSCLC mice, and safety evaluation in human MUC1 transgenic mice.","limitations":"Mouse xenograft model; MUC1 glycosylation varies between patients; small animal numbers; clinical translation requires human safety/efficacy testing."},{"rthcId":"RPEP-05052","title":"Functional Connectomic Approach to Studying Selank and Semax Effects.","authors":"Panikratova, Ya R; Lebedeva, I S; Sokolov, O Yu; Rumshiskaya, A D; Kupriyanov, D A; Kost, N V; Myasoedov, N F","year":2020,"journal":"Doklady biological sciences : proceedings of the Academy of Sciences of the USSR, Biological sciences sections, 490(1), 9-11","doi":"10.1134/S001249662001007X","pmid":"32342318","tags":["selank","semax","neuropeptides"],"studyType":"rct","evidenceStrength":"preliminary","keyFinding":"Both Selank and Semax modulated functional connectivity between right amygdala and right temporal cortex regions (fusiform, inferior/middle temporal, parahippocampal gyri) with both shared and peptide-specific effects.","whyItMatters":"This is the first human fMRI study showing how Selank and Semax change whole-brain connectivity, providing a neurobiological basis for their anxiolytic and cognitive-enhancing effects.","specificNumbers":"52 participants; 3 groups (Selank, Semax, placebo); fMRI at baseline, 5 min, 20 min post-injection","methodology":"Randomized, placebo-controlled trial with 52 healthy participants receiving Selank, Semax, or placebo injections, with resting-state fMRI at baseline, 5 min, and 20 min post-injection.","limitations":"Small sample per group (~17 each); only 20-minute follow-up; resting-state fMRI without cognitive task; healthy participants may not reflect clinical populations."},{"rthcId":"RPEP-05053","title":"The Antimicrobial Peptide Human Beta-Defensin 2 Inhibits Biofilm Production of Pseudomonas aeruginosa Without Compromising Metabolic Activity.","authors":"Parducho, Kevin R; Beadell, Brent; Ybarra, Tiffany K; Bush, Mabel; Escalera, Erick; Trejos, Aldo T; Chieng, Andy; Mendez, Marlon; Anderson, Chance; Park, Hyunsook; Wang, Yixian; Lu, Wuyuan; Porter, Edith","year":2020,"journal":"Frontiers in immunology, 11, 805","doi":"10.3389/fimmu.2020.00805","pmid":"32457749","tags":["antimicrobial-peptides","infection"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"HBD2 at nanomolar concentrations significantly inhibits P. aeruginosa biofilm without compromising metabolic activity, through outer membrane protein alterations rather than quorum sensing interference.","whyItMatters":"Biofilm is a major factor in chronic infections that resist antibiotics. A natural peptide that blocks biofilm without killing bacteria could provide a new anti-biofilm strategy that does not drive resistance.","specificNumbers":"Nanomolar HBD2 concentrations; biofilm reduced without metabolic activity change; outer membrane protein profile altered; effect seen in P. aeruginosa and A. baumannii","methodology":"In-vitro study comparing HBD2 and HBD3 effects on P. aeruginosa biofilm formation, metabolic activity, gene expression, quorum sensing, outer membrane proteins (AFM), and extending findings to A. baumannii.","limitations":"In-vitro study with two bacterial species; exact molecular targets in the outer membrane not identified; clinical relevance of nanomolar concentrations at infection sites not established."},{"rthcId":"RPEP-05054","title":"BPC 157 Rescued NSAID-cytotoxicity Via Stabilizing Intestinal Permeability and Enhancing Cytoprotection.","authors":"Park, Jong M; Lee, Ho J; Sikiric, Predrag; Hahm, Ki B","year":2020,"journal":"Current pharmaceutical design, 26(25), 2971-2981","doi":"10.2174/1381612826666200523180301","pmid":"32445447","tags":["bpc-157","gut-healing"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"BPC-157 rescues NSAID-induced gut damage by stabilizing intestinal permeability and providing cytoprotection across the GI tract and other organs, potentially addressing leaky gut syndrome.","whyItMatters":"NSAID use is widespread and GI side effects affect millions. A peptide that specifically protects the gut lining from NSAID damage could prevent a major source of medication-related morbidity.","specificNumbers":"BPC-157 counteracts NSAIDs, alcohol, bile acids, stress on gut permeability; protective in stomach, intestine, skin, liver, pancreas, heart, brain","methodology":"Narrative review compiling evidence for BPC-157 cytoprotective and organoprotective effects against NSAID-induced damage, intestinal permeability changes, and endothelial injury.","limitations":"Review without new experimental data; most evidence from animal studies; human clinical trials for NSAID gastroprotection are lacking; mechanisms not fully elucidated."},{"rthcId":"RPEP-05055","title":"Glycaemic and non-glycaemic efficacy of once-weekly GLP-1 receptor agonists in people with type 2 diabetes.","authors":"Patel, Dhiren","year":2020,"journal":"Journal of clinical pharmacy and therapeutics, 45 Suppl 1(Suppl 1), 28-42","doi":"10.1111/jcpt.13224","pmid":"32910489","tags":["glp-1","semaglutide","dulaglutide","exenatide","diabetes","cardiovascular"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Semaglutide subcutaneous was superior to dulaglutide and exenatide ER for HbA1c and weight reduction in head-to-head trials, with both semaglutide and dulaglutide showing cardiovascular and renal benefits.","whyItMatters":"Clinicians need to choose between GLP-1 drugs for their patients. This comprehensive comparison helps match the right drug to the right patient based on glycemic, weight, and cardiovascular priorities.","specificNumbers":"31 trials; semaglutide superior to dulaglutide and exenatide ER for HbA1c and weight; CV benefits for semaglutide and dulaglutide","methodology":"Narrative review of 31 Phase 3 clinical trials from dulaglutide, exenatide ER, and semaglutide clinical development programs, comparing glycemic, weight, cardiovascular, and renal outcomes.","limitations":"Narrative review — not a formal meta-analysis; cross-trial comparisons have limitations; exenatide ER data less comprehensive than semaglutide; head-to-head vs. daily GLP-1 RAs had mixed results."},{"rthcId":"RPEP-05056","title":"Cardiovascular Effects of Dipeptidyl Peptidase-4 Inhibitors and Glucagon-Like Peptide-1 Receptor Agonists: a Review for the General Cardiologist.","authors":"Patel, Kershaw V; Sarraju, Ashish; Neeland, Ian J; McGuire, Darren K","year":2020,"journal":"Current cardiology reports, 22(10), 105","doi":"10.1007/s11886-020-01355-5","pmid":"32770420","tags":["glp-1","cardiovascular","liraglutide","semaglutide","dulaglutide"],"studyType":"review","evidenceStrength":"strong","keyFinding":"GLP-1 RAs (liraglutide, semaglutide, albiglutide, dulaglutide) reduce MACE in T2DM patients with CV disease, while DPP-4 inhibitors show CV safety but no MACE benefit, with saxagliptin increasing HF risk.","whyItMatters":"Cardiologists increasingly manage diabetes medications for cardiovascular risk reduction. Understanding which incretin drugs provide heart protection — and which do not — directly impacts patient outcomes.","specificNumbers":"Liraglutide, semaglutide, albiglutide, dulaglutide reduce MACE; saxagliptin increases HF risk; sitagliptin and linagliptin HF-neutral","methodology":"Narrative review of cardiovascular outcome trials for DPP-4 inhibitors and GLP-1 receptor agonists, written for the general cardiologist audience.","limitations":"Review without new data; CV benefit shown in high-risk patients — may not apply to lower-risk populations; not all GLP-1 RAs tested in dedicated CV outcome trials."},{"rthcId":"RPEP-05057","title":"Polyplexes System to Enhance the LL-37 Antimicrobial Peptide Expression in Human Skin Cells.","authors":"Patiño Vargas, Maria Isabel; Mesa Cadavid, Mónica; Arenas Gómez, Claudia Marcela; Diosa Arango, Johnatan; Restrepo Múnera, Luz Marina; Becerra Colorado, Natalia Yiset","year":2020,"journal":"Tissue engineering. Part A, 26(7-8), 400-410","doi":"10.1089/ten.TEA.2019.0196","pmid":"31805827","tags":["ll-37","peptide-delivery","infection","skin-repair"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Linear PEI/pDNA polyplexes successfully transfected human keratinocytes and fibroblasts to overexpress LL-37, with supernatants reducing S. aureus growth by 95.8%.","whyItMatters":"Drug-resistant skin infections in wound patients have high mortality. Genetically engineering skin substitutes to produce their own antimicrobial peptides could provide continuous, localized infection defense.","specificNumbers":"95.8% S. aureus growth reduction; polyplex sizes 400 nm (linear PEI) and 250 nm (branched PEI); surface charge +30 mV; N/P ratio 19","methodology":"In-vitro study optimizing PEI polymer/pDNA polyplex formation for transfection of primary human keratinocytes and fibroblasts, measuring LL-37 expression and antimicrobial activity against S. aureus.","limitations":"In-vitro proof of concept; cytotoxicity concerns with branched PEI; 3D skin substitute construction not yet demonstrated; in-vivo wound healing not tested; limited to one bacterial strain."},{"rthcId":"RPEP-05058","title":"Free Fatty Acid-Induced Peptide YY Expression Is Dependent on TG Synthesis Rate and Xbp1 Splicing.","authors":"Paton, Chad M; Son, Yura; Vaughan, Roger A; Cooper, Jamie A","year":2020,"journal":"International journal of molecular sciences, 21(9)","doi":"10.3390/ijms21093368","pmid":"32397573","tags":["neuropeptides","weight-loss","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Free fatty acids induce PYY via Xbp1 activation in L-cells, but triglyceride re-esterification rate determines signal duration — chronic high-fat diets accelerate re-esterification and blunt PYY response.","whyItMatters":"Understanding why obese individuals feel less full after meals could lead to therapies that restore satiety signaling by slowing intestinal fat re-esterification.","specificNumbers":"MUFA re-esterified fastest with lowest PYY; chronic HFD increased TG synthesis rate; Xbp1s sufficient to induce PYY","methodology":"Combined in-vitro L-cell studies and animal feeding experiments testing different fatty acid types, re-esterification rates, and Xbp1 signaling in PYY production, with chronic high-fat diet comparison.","limitations":"Animal study with in-vitro components; human L-cell responses may differ; Xbp1 pathway complexity not fully characterized; specific fatty acid effects vary."},{"rthcId":"RPEP-05059","title":"An Update on Antimicrobial Peptides (AMPs) and Their Delivery Strategies for Wound Infections.","authors":"Patrulea, Viorica; Borchard, Gerrit; Jordan, Olivier","year":2020,"journal":"Pharmaceutics, 12(9)","doi":"10.3390/pharmaceutics12090840","pmid":"32887353","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05060","title":"Effect of intramolecular disulfide bond of bovine lactoferricin on its molecular structure and antibacterial activity against Trueperella pyogenes separated from cow milk with mastitis.","authors":"Pei, Jie; Xiong, Lin; Chu, Min; Guo, Xian; Yan, Ping","year":2020,"journal":"BMC veterinary research, 16(1), 401","doi":"10.1186/s12917-020-02620-z","pmid":"33097042","tags":["antimicrobial-peptides","peptide-design","bioactive-food-peptides"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"The intramolecular disulfide bond in bLfcin increased β-turn structure and enhanced antibacterial activity against T. pyogenes mastitis isolates compared to derivatives without the bond.","whyItMatters":"Bovine mastitis causes significant economic losses in dairy farming. Understanding what makes lactoferricin effective against mastitis pathogens could lead to peptide-based udder treatments.","specificNumbers":"3 peptide variants; DB form had most beta-turn structure; all more active against T. pyogenes than E. coli","methodology":"In-vitro study synthesizing three bLfcin variants, characterizing structure by circular dichroism in different ionic/hydrophobic conditions, and testing antibacterial activity against T. pyogenes and E. coli.","limitations":"In-vitro study only; limited bacterial strains tested; clinical relevance for mastitis treatment not established; mechanism of enhanced activity beyond structural changes not explored."},{"rthcId":"RPEP-05061","title":"Acidosis induces antimicrobial peptide expression and resistance to uropathogenic E. coli infection in kidney collecting duct cells via HIF-1α.","authors":"Peng, Hu; Purkerson, Jeffrey M; Freeman, Robert S; Schwaderer, Andrew L; Schwartz, George J","year":2020,"journal":"American journal of physiology. Renal physiology, 318(2), F468-F474","doi":"10.1152/ajprenal.00228.2019","pmid":"31841391","tags":["antimicrobial-peptides","kidney","infection","immune-function"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Acid loading of kidney collecting duct cells induces cathelicidin and beta-defensin expression via HIF-1α, increasing resistance to uropathogenic E. coli infection.","whyItMatters":"Urinary tract infections are extremely common and increasingly antibiotic-resistant. Understanding the kidney's natural AMP defense could lead to new strategies to prevent or treat kidney infections.","specificNumbers":"pH 6.8 for 24h; induced cathelicidin, Defb2, Defb26; HIF-1α inhibitor PX-478 reduced E. coli resistance","methodology":"In-vitro study using M-1 mouse collecting duct cells under acidic conditions (pH 6.8), measuring AMP gene expression and bacterial resistance with HIF-1α inhibitor and prolyl hydroxylase inhibitor controls.","limitations":"In-vitro mouse cell line study; human kidney cell responses may differ; in-vivo pyelonephritis model not tested; HIF stabilization has broad effects beyond AMP induction."},{"rthcId":"RPEP-05062","title":"Peptide Nanomaterials for Drug Delivery Applications.","authors":"Pentlavalli, Sreekanth; Coulter, Sophie; Laverty, Garry","year":2020,"journal":"Current protein & peptide science, 21(4), 401-412","doi":"10.2174/1389203721666200101091834","pmid":"31893991","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05063","title":"Calcitonin Gene-Related Peptide Antagonists as a Savior in Episodic and Chronic Migraine: A Review.","authors":"Pervez, Hira; Khemani, Lavina; Khan, Mahrukh A; Seedat, Ahmed M; Roshan, Fnu","year":2020,"journal":"Cureus, 12(6), e8711","doi":"10.7759/cureus.8711","pmid":"32699706","tags":["neuropeptides","pain"],"studyType":"review","evidenceStrength":"strong","keyFinding":"All four anti-CGRP monoclonal antibodies demonstrated significant reductions in monthly migraine days across multiple Phase 2-3 clinical trials, with favorable safety profiles compared to existing preventive treatments.","whyItMatters":"Migraine is the second leading cause of disability worldwide, and many patients fail existing preventive treatments or stop taking them due to side effects. CGRP-targeting antibodies represent the first migraine-specific preventive therapy class.","specificNumbers":"4 monoclonal antibodies; migraine is 2nd leading cause of disability; monthly or quarterly dosing","methodology":"Narrative review of published clinical trial data, ongoing trials, and pharmacological evidence for CGRP-targeting monoclonal antibodies in episodic and chronic migraine prevention.","limitations":"Review format — no new trial data. Long-term safety data beyond trial periods still accumulating. Cost and accessibility remain barriers for many patients. Does not address non-responders to anti-CGRP therapy."},{"rthcId":"RPEP-05064","title":"Synthesis and Ex Vivo Trans-Corneal Permeation of Penetratin Analogues as Ophthalmic Carriers: Preliminary Results.","authors":"Pescina, Silvia; Sala, Marina; Scala, Maria Carmina; Santi, Patrizia; Padula, Cristina; Campiglia, Pietro; Ostacolo, Carmine; Nicoli, Sara","year":2020,"journal":"Pharmaceutics, 12(8)","doi":"10.3390/pharmaceutics12080728","pmid":"32756470","tags":["cell-penetrating","peptide-delivery","eye-health"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"All synthesized penetratin analogues demonstrated measurable trans-corneal diffusion despite their hydrophilic nature and ~1.6 kDa size, though none achieved the penetration efficiency of full-length penetratin.","whyItMatters":"Eye drug delivery is challenging because the cornea blocks most molecules. Cell-penetrating peptides could carry drugs across this barrier without invasive procedures like injections.","specificNumbers":"~1.6 kDa molecular weight; all analogs showed trans-corneal diffusion; none matched full-length penetratin (16 aa)","methodology":"Synthesized fluorescently labeled short analogues of penetratin and its reversed sequence via mimotopic approach, then tested trans-corneal permeation ex vivo using freshly explanted porcine corneas. Structural analysis performed via circular dichroism.","limitations":"Preliminary results only. Ex vivo porcine tissue may not fully replicate living human cornea. No therapeutic cargo was tested — only the peptide carriers themselves. No clear structure-activity relationship was established."},{"rthcId":"RPEP-05065","title":"Safety of injectable semaglutide for type 2 diabetes.","authors":"Peter, Rajesh; Bain, Steve C","year":2020,"journal":"Expert opinion on drug safety, 19(7), 785-798","doi":"10.1080/14740338.2020.1772230","pmid":"32428416","tags":["semaglutide","glp-1","diabetes","cardiovascular","eye-health","side-effects"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Semaglutide demonstrated cardiovascular superiority in SUSTAIN 6, with a safety profile typical of GLP-1RAs. The only concerning signal was increased diabetic retinopathy events, likely related to rapid glucose lowering rather than direct drug toxicity.","whyItMatters":"Semaglutide has become one of the most widely prescribed diabetes medications. Understanding its full safety profile helps clinicians make informed prescribing decisions, especially for patients with existing eye complications.","specificNumbers":"SUSTAIN 6 showed CV superiority; GI side effects most common; increased DR events; modest gallbladder signal; no confirmed MTC or pancreatitis risk","methodology":"Comprehensive review of published safety data from the SUSTAIN Phase 3 clinical trial program and related literature on once-weekly GLP-1 receptor agonist safety.","limitations":"Review of existing trial data — no new safety analysis. Long-term safety beyond trial durations not fully known at time of publication. Post-marketing real-world safety data was still accumulating."},{"rthcId":"RPEP-05066","title":"Melanotan II: a possible cause of renal infarction: review of the literature and case report.","authors":"Peters, Björn; Hadimeri, Henrik; Wahlberg, Rebecka; Afghahi, Henri","year":2020,"journal":"CEN case reports, 9(2), 159-161","doi":"10.1007/s13730-020-00447-z","pmid":"31953620","tags":["melanotan","adverse-effects"],"studyType":"case-report","evidenceStrength":"case-report","keyFinding":"A case of renal infarction (blood flow blockage to the kidney) was reported in a patient using Melanotan II, a non-selective melanocortin receptor agonist used illicitly for skin tanning and sexual enhancement. The renal infarction was most likely attributed to the Melanotan II use.\n\nThe authors propose two possible mechanisms for the kidney injury: a thrombotic (blood clot) effect from the drug's pharmacological action, and a possible direct toxic effect on kidney tissue. Previous reports had already linked Melanotan II to rhabdomyolysis (muscle breakdown) and kidney failure, and this case adds renal infarction to the list of serious adverse events.","whyItMatters":"Melanotan II is widely available through unregulated online markets and used by thousands of people for tanning and sexual enhancement, despite never being approved for human use by any regulatory agency. Most users are unaware of serious risks like kidney damage. This case report adds renal infarction — a potentially life-threatening condition — to the growing list of documented harms. It also highlights that renal infarction is frequently misdiagnosed or diagnosed late, meaning the actual incidence in Melanotan II users may be higher than reported.","specificNumbers":"1 case of renal infarction · Non-selective melanocortin receptor agonist · Prior reports of rhabdomyolysis and renal failure","methodology":"Case report of a single patient who developed renal infarction in the setting of Melanotan II use, combined with a literature review of Melanotan II's known effects on the kidneys.","limitations":"This is a single case report, which cannot prove causation — only an association between Melanotan II use and renal infarction. The patient may have had other risk factors not fully described. The exact mechanism of injury remains hypothetical. Case reports represent the lowest level of clinical evidence."},{"rthcId":"RPEP-05067","title":"Comparison of personal and shared frameshift neoantigen vaccines in a mouse mammary cancer model.","authors":"Peterson, Milene; Murphy, Sierra Nicole; Lainson, John; Zhang, Jian; Shen, Luhui; Diehnelt, Chris W; Johnston, Stephen Albert","year":2020,"journal":"BMC immunology, 21(1), 25","doi":"10.1186/s12865-020-00350-3","pmid":"32370785","tags":["cancer","immune-function"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Both personal cancer vaccines (PCVs) and the shared FAST vaccine reduced primary tumor incidence, tumor growth, and lung metastases as monotherapies and in combination with anti-PD-L1/CTLA-4 checkpoint inhibitors. The FAST vaccine induced robust T-cell responses.","whyItMatters":"Personalized cancer vaccines are expensive, slow to produce, and not feasible for all patients. If shared antigen vaccines work as well, cancer immunotherapy could become accessible to far more patients.","specificNumbers":"200 FSP microarray; top 10 peptides per vaccine; both PCV and FAST reduced tumors and metastases; combined with anti-PD-L1 and anti-CTLA-4","methodology":"Mouse mammary cancer model (4T1) with frameshift peptide microarray screening. Compared personal vaccines (top 10 per mouse) vs shared FAST vaccines (top 10 across all mice). Evaluated with/without checkpoint inhibitors. Measured tumor clearance, metastases, and immune response via ELISPOT, ELISA, and flow cytometry.","limitations":"Mouse model only — human tumors are more heterogeneous. The 4T1 model may not represent all solid tumor types. Sample sizes not clearly reported. RNA-based frameshift antigens in human cancers need validation."},{"rthcId":"RPEP-05068","title":"Tolerogenic Immunomodulation by PEGylated Antigenic Peptides.","authors":"Pfeil, Jennifer; Simonetti, Mario; Lauer, Uta; Volkmer, Rudolf; von Thülen, Bianca; Durek, Pawel; Krähmer, Ralf; Leenders, Frank; Hamann, Alf; Hoffmann, Ute","year":2020,"journal":"Frontiers in immunology, 11, 529035","doi":"10.3389/fimmu.2020.529035","pmid":"33162973","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05069","title":"Signalling, trafficking and glucoregulatory properties of glucagon-like peptide-1 receptor agonists exendin-4 and lixisenatide.","authors":"Pickford, Philip; Lucey, Maria; Fang, Zijian; Bitsi, Stavroula; de la Serna, Jorge Bernardino; Broichhagen, Johannes; Hodson, David J; Minnion, James; Rutter, Guy A; Bloom, Stephen R; Tomas, Alejandra; Jones, Ben","year":2020,"journal":"British journal of pharmacology, 177(17), 3905-3923","doi":"10.1111/bph.15134","pmid":"32436216","tags":["exenatide","glp-1","receptor-signaling","peptide-design"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Lixisenatide showed 5-fold lower cAMP signaling potency than exendin-4 despite equal binding affinity, with slower GLP-1 receptor recycling. An N-terminal His1→Phe1 substitution improved the pharmacology of both ligands.","whyItMatters":"Understanding why structurally similar GLP-1 drugs perform differently helps design better next-generation peptide therapeutics with optimized signaling and receptor handling properties.","specificNumbers":"5x lower cAMP potency for lixisenatide; equal binding affinity; slower receptor recycling; His1→Phe1 improved both peptides","methodology":"In vitro signaling and trafficking assays across multiple cell types using fluorescent ligands and time-resolved FRET. In vivo testing of anti-hyperglycemic and anorectic effects in mice. Compared parent ligands and biased N-terminal analogues.","limitations":"Mouse studies may not fully predict human pharmacology. Specific sample sizes not reported. The Phe1 analogues are not clinically approved — additional development needed."},{"rthcId":"RPEP-05070","title":"Interaction of camel Lactoferrin derived peptides with DNA: a molecular dynamics study.","authors":"Pirkhezranian, Zana; Tahmoorespur, Mojtaba; Daura, Xavier; Monhemi, Hassan; Sekhavati, Mohammad Hadi","year":2020,"journal":"BMC genomics, 21(1), 60","doi":"10.1186/s12864-020-6458-7","pmid":"31959108","tags":["antimicrobial-peptides","peptide-design"],"studyType":"computational","evidenceStrength":"preliminary","keyFinding":"CLFchimera showed the highest DNA binding affinity among the three peptides. At a concentration of four copies per DNA segment, it began breaking hydrogen bonds between DNA strands, suggesting a concentration-dependent mechanism of bacterial killing.","whyItMatters":"Understanding exactly how antimicrobial peptides kill bacteria at the molecular level enables rational redesign of more potent peptide antibiotics to combat drug-resistant infections.","specificNumbers":"3 peptides; 200 ns simulations; 4 copies of CLFchimera broke DNA hydrogen bonds; no sequence preference","methodology":"Molecular dynamics simulations over 200 ns modeling interactions between three camel lactoferrin-derived peptides (CLFampin, CLFcin, CLFchimera) and DNA. Binding free energies calculated to identify key interaction residues.","limitations":"Computational study only — no wet-lab validation of the predicted DNA interactions. Simulated conditions may not perfectly replicate the intracellular bacterial environment. Does not address how peptides first enter bacterial cells."},{"rthcId":"RPEP-05071","title":"Transplantation of Endothelial Progenitor Cells in Obese Diabetic Rats Following Myocardial Infarction: Role of Thymosin Beta-4.","authors":"Poh, Kian Keong; Lee, Poay Sian Sabrina; Djohan, Andie Hartanto; Galupo, Mary Joyce; Songco, Geronica Gorospe; Yeo, Tiong Cheng; Tan, Huay Cheem; Richards, Arthur Mark; Ye, Lei","year":2020,"journal":"Cells, 9(4)","doi":"10.3390/cells9040949","pmid":"32290541","tags":["thymosin-beta-4","cardiovascular","diabetes"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Tβ4 at 10 ng/mL improved diabetic EPC migration, tubule formation, and angiogenic factor secretion in vitro, and increased capillary density in vivo, but only non-Tβ4-treated EPCs significantly improved left ventricular ejection fraction.","whyItMatters":"Heart disease is the leading killer of diabetic patients, and their stem cells are impaired. Finding ways to restore diabetic stem cell function could improve outcomes after heart attacks in this vulnerable population.","specificNumbers":"10 ng/mL Tb4; MRI at 2, 4, 12 weeks; increased capillary density and c-Kit+ cells; no EF improvement","methodology":"In vitro: Tβ4 treatment of diabetic EPCs measuring migration, tube formation, and growth factor secretion. In vivo: intramyocardial injection of Tβ4-treated vs untreated diabetic EPCs in obese diabetic rats after induced heart attack, measuring capillary density, progenitor cell recruitment, and cardiac function.","limitations":"Small animal model with unspecified group sizes. The paradox of improved vessel formation but not heart function is unexplained. Single Tβ4 dose tested. Short follow-up period likely."},{"rthcId":"RPEP-05072","title":"Incomplete Freund's adjuvant reduces arginase and enhances Th1 dominance, TLR signaling and CD40 ligand expression in the vaccine site microenvironment.","authors":"Pollack, Karlyn E; Meneveau, Max O; Melssen, Marit M; Lynch, Kevin T; Koeppel, Alexander F; Young, Samuel J; Turner, Stephen; Kumar, Pankaj; Sol-Church, Katia; Mauldin, Ileana S; Slingluff, Craig L","year":2020,"journal":"Journal for immunotherapy of cancer, 8(1)","doi":"10.1136/jitc-2020-000544","pmid":"32350119","tags":["cancer","immune-function"],"studyType":"clinical-observational","evidenceStrength":"preliminary","keyFinding":"Same-site vaccination (SSV×3) with peptides in IFA dramatically enhanced Th1 markers (TBX21, IFNγ, STAT1), reduced immunosuppressive ARG1, increased TLR adapter expression, and promoted tertiary lymphoid structure formation at the vaccine site.","whyItMatters":"Understanding how adjuvants and vaccination schedules shape the local immune environment can help optimize cancer vaccine strategies for stronger anti-tumor responses.","specificNumbers":"27 patients; CD40/CD40L p<0.0001; SSV×3 enhanced TBX21, IFN-γ, STAT1; decreased GATA3 and ARG1","methodology":"Clinical observational study with VSME biopsies from 27 melanoma patients across two clinical trials (NCT00705640, NCT01585350). RNAseq gene expression analysis comparing single vaccination, repeated same-site vaccination, and controls (normal skin, IFA-only).","limitations":"Observational biopsy study — no direct tumor outcome data. Small sample size (n=27). Only melanoma patients studied. Gene expression does not always correlate with functional immune responses."},{"rthcId":"RPEP-05073","title":"Comparison of magnetic bead surface functionalities for the immunopurification of growth hormone-releasing hormones prior to liquid chromatography-high resolution mass spectrometry.","authors":"Pont, Laura; Alechaga, Élida; Terrero, Alejandro; Monfort, Núria; Ventura, Rosa","year":2020,"journal":"Journal of chromatography. A, 1631, 461548","doi":"10.1016/j.chroma.2020.461548","pmid":"32971474","tags":["hormone-optimization","regulatory","cjc-1295"],"studyType":"methodology","evidenceStrength":"not-applicable","keyFinding":"Optimized magnetic bead immunopurification coupled with LC-HRMS achieved a limit of detection of 0.2 ng/mL and limit of identification of 0.5 ng/mL for GHRH analogues in human urine, with acceptable precision and specificity.","whyItMatters":"Athletes may misuse growth hormone-releasing peptides to enhance performance. Reliable detection methods at very low concentrations are essential for anti-doping enforcement.","specificNumbers":"LOD 0.2 ng/mL; LOI 0.5 ng/mL; intra-day CV <15%; inter-day CV <25%; 4 target peptides","methodology":"Compared magnetic beads with different surface functionalities, binding capacities, and affinity chemistries for immunopurification. Analyzed by liquid chromatography coupled to Quadrupole-Orbitrap high-resolution mass spectrometry. Full method validation including specificity, precision, matrix effects, and detection limits.","limitations":"Methodology study — does not address prevalence of GHRH doping. Detection limits may still miss very low-level use. Antibody-based methods depend on cross-reactivity with new analogues."},{"rthcId":"RPEP-05074","title":"Safety and efficacy of Cerebrolysin in acute brain injury and neurorecovery: CAPTAIN I-a randomized, placebo-controlled, double-blind, Asian-Pacific trial.","authors":"Poon, W; Matula, C; Vos, P E; Muresanu, D F; von Steinbüchel, N; von Wild, K; Hömberg, V; Wang, E; Lee, T M C; Strilciuc, S; Vester, J C","year":2020,"journal":"Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 41(2), 281-293","doi":"10.1007/s10072-019-04053-5","pmid":"31494820","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05075","title":"In Vivo Histone Labeling Using Ultrafast trans-Splicing Inteins.","authors":"Prescott, Nicholas A; David, Yael","year":2020,"journal":"Methods in molecular biology (Clifton, N.J.), 2133, 201-219","doi":"10.1007/978-1-0716-0434-2_10","pmid":"32144669","tags":["peptide-design"],"studyType":"methodology","evidenceStrength":"not-applicable","keyFinding":"Protein trans-splicing using ultrafast split inteins can deliver synthetic modifications to chromatinized histones in living cells, creating native peptide bonds without leaving scars or tags.","whyItMatters":"Studying histone modifications in their natural cellular context is crucial for understanding gene regulation. This method enables researchers to add specific modifications to chromatin in living cells rather than studying them in test tubes.","specificNumbers":"Split intein PTS; native peptide bonds; demonstrated with fluorophore incorporation into chromatin","methodology":"Protocol development for in vivo protein trans-splicing using split inteins to modify histones. Demonstrated by incorporating a small molecule fluorophore into chromatinized histones in live cells.","limitations":"Methodology paper — demonstrates proof of concept with fluorophore labeling but does not characterize functional consequences. Split intein delivery efficiency in different cell types not addressed."},{"rthcId":"RPEP-05076","title":"Apoptosis-inducing peptide loaded in PLGA nanoparticles induces anti-tumor effects in vivo.","authors":"Priwitaningrum, Dwi L; Jentsch, Julian; Bansal, Ruchi; Rahimian, Sima; Storm, Gert; Hennink, Wim E; Prakash, Jai","year":2020,"journal":"International journal of pharmaceutics, 585, 119535","doi":"10.1016/j.ijpharm.2020.119535","pmid":"32534162","tags":["cell-penetrating","cancer","peptide-delivery"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Smac-CPP nanoparticles combined with doxorubicin reduced tumor growth by 85% in vivo, with decreased Ki-67 proliferation staining and increased cleaved caspase-3 apoptosis staining in tumors.","whyItMatters":"Cancer cells often resist apoptosis, limiting chemotherapy effectiveness. Delivering apoptosis-triggering peptides directly into tumor cells could sensitize them to standard chemotherapy drugs.","specificNumbers":"85% tumor growth reduction; 8-mer Smac + 14-mer CPP; decreased Ki-67, increased cleaved caspase-3","methodology":"Synthesized chimeric Smac-CPP peptide (8-mer Smac + 14-mer CPP), encapsulated in PLGA nanoparticles. In vitro testing in 4T1 mammary tumor cells for uptake, viability, and caspase activation. In vivo combination therapy with doxorubicin in mouse breast cancer model.","limitations":"Mouse model only with unspecified group sizes. PLGA nanoparticle manufacturing scalability not addressed. Long-term toxicity and biodistribution not reported. Only tested with one chemotherapy drug."},{"rthcId":"RPEP-05077","title":"Mouse defensin beta 20 (Defb20) is expressed specifically in the caput region of the epididymis and regulated by androgen and testicular factors.","authors":"Pujianto, Dwi Ari; Muliawati, Dewi; Rizki, Meidika Dara; Parisudha, Annisa; Hardiyanto, Lutfi","year":2020,"journal":"Reproductive biology, 20(4), 536-540","doi":"10.1016/j.repbio.2020.09.003","pmid":"33060057","tags":["antimicrobial-peptides","fertility"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Defb20 is exclusively expressed in the caput epididymis, down-regulated by gonadectomy and efferent duct ligation, and first expressed at postnatal day 20, indicating androgen-dependent regulation linked to sperm maturation.","whyItMatters":"Understanding how defensin peptides contribute to sperm maturation could reveal new targets for male fertility treatments or non-hormonal contraceptive approaches.","specificNumbers":"Exclusive epididymis expression; highest in caput; down-regulated by castration and EDL; onset at postnatal day 20","methodology":"Bioinformatic analysis of functional domains and signal peptide. qRT-PCR for tissue distribution, androgen dependency (gonadectomy), testicular factor dependency (efferent duct ligation), and developmental expression profiling.","limitations":"Mouse study only — human relevance not established. Functional role inferred from expression patterns rather than direct functional experiments. Protein-level expression and localization not confirmed."},{"rthcId":"RPEP-05078","title":"Drug Conjugation Induced Modulation of Structural and Membrane Interaction Features of Cationic Cell-Permeable Peptides.","authors":"Pári, Edit; Horváti, Kata; Bősze, Szilvia; Biri-Kovács, Beáta; Szeder, Bálint; Zsila, Ferenc; Kiss, Éva","year":2020,"journal":"International journal of molecular sciences, 21(6)","doi":"10.3390/ijms21062197","pmid":"32235796","tags":["cell-penetrating","peptide-delivery","infection"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"INH-CPP conjugates showed conjugation-induced structural and membrane interaction changes that correlated with each other; Penetratin and Transportan conjugates had similar cell uptake but different subcellular localization and anti-Mtb activity.","whyItMatters":"TB kills over a million people annually. CPP-delivered drugs that reach the right intracellular compartments could improve treatment of this hard-to-reach pathogen.","specificNumbers":"Multiple CPPs tested; Penetratin and Transportan conjugates had similar uptake but different localization and anti-Mtb activity","methodology":"In-vitro study using Langmuir balance membrane interaction assays, circular dichroism spectroscopy, AFM imaging, and cellular uptake/anti-Mtb activity assays with INH-CPP conjugates.","limitations":"In-vitro study with one cancer cell line; limited Mtb strains tested; conjugation may affect INH drug activity independently of delivery; in-vivo pharmacokinetics not assessed."},{"rthcId":"RPEP-05079","title":"Bioactive Peptides and Dietary Polyphenols: Two Sides of the Same Coin.","authors":"Pérez-Gregorio, Rosa; Soares, Susana; Mateus, Nuno; de Freitas, Victor","year":2020,"journal":"Molecules (Basel, Switzerland), 25(15)","doi":"10.3390/molecules25153443","pmid":"32751126","tags":["bioactive-food-peptides","bioavailability"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Polyphenol-bioactive peptide interactions during digestion can alter the bioavailability and biological function of both compounds, with implications for functional food and nutraceutical design.","whyItMatters":"Many people take polyphenol and peptide supplements together or eat foods rich in both. If these compounds interact negatively, the health benefits of one or both could be reduced.","specificNumbers":"Polyphenols can precipitate proteins/peptides; interactions affected by pH, temperature, processing","methodology":"Narrative review examining polyphenol-protein/peptide interactions and their effects on digestion, absorption, metabolism, and bioactivity of both compound classes.","limitations":"Review identifies a knowledge gap rather than providing definitive answers; most interaction studies are in vitro; in-vivo human data on combined polyphenol-peptide bioavailability is scarce."},{"rthcId":"RPEP-05080","title":"Hitchhiking with Nature: Snake Venom Peptides to Fight Cancer and Superbugs.","authors":"Pérez-Peinado, Clara; Defaus, Sira; Andreu, David","year":2020,"journal":"Toxins, 12(4)","doi":"10.3390/toxins12040255","pmid":"32326531","tags":["venom-peptides","antimicrobial-peptides","cancer"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Snake venom-derived peptides demonstrate validated antimicrobial and anticancer activities, with several compounds showing dual functionality against both drug-resistant bacteria and tumor cells through membrane-disrupting mechanisms.","whyItMatters":"With antibiotic resistance rising and cancer treatment options still limited, snake venom peptides offer a largely untapped source of compounds that could address both crises simultaneously.","specificNumbers":"Multiple SV peptides with validated AMP and ACP activity; existing SV-based cardiovascular drugs on market","methodology":"Comprehensive literature review analyzing experimentally validated and computationally predicted antimicrobial and anticancer peptides derived from snake venoms, covering in vitro and in vivo studies.","limitations":"As a review, no new experimental data is presented. Many cataloged peptides remain at early discovery stages. Translation from venom compounds to clinical drugs faces challenges including stability, toxicity, and manufacturing scale."},{"rthcId":"RPEP-05081","title":"Tumor Cell Attack by Crotalicidin (Ctn) and Its Fragment Ctn[15-34]: Insights into Their Dual Membranolytic and Intracellular Targeting Mechanism.","authors":"Pérez-Peinado, Clara; Valle, Javier; Freire, João M; Andreu, David","year":2020,"journal":"ACS chemical biology, 15(11), 2945-2957","doi":"10.1021/acschembio.0c00596","pmid":"33021779","tags":["venom-peptides","cancer","antimicrobial-peptides"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Ctn and Ctn[15-34] kill leukemia cells via dual membranolytic and intracellular mechanisms, with 17-fold and 7-fold tumor selectivity respectively, and protease stability up to 18-24 hours.","whyItMatters":"Cancer cells that resist conventional drugs may be vulnerable to membrane-disrupting venom peptides that bypass resistance mechanisms — and the high tumor selectivity reduces toxicity concerns.","specificNumbers":"Selectivity: Ctn 17:1, Ctn[15-34] 7:1; serum stability up to 24h (Ctn) and 18h (fragment)","methodology":"In-vitro study using flow cytometry, microscopy, and affinity purification proteomics to characterize antitumoral mechanisms and selectivity of Ctn and Ctn[15-34] against pro-monocytic leukemia cells.","limitations":"In-vitro study with one leukemia cell line; selectivity ratios may differ across cancer types; in-vivo efficacy and toxicity not tested; mechanism details need further validation."},{"rthcId":"RPEP-05082","title":"Protection against oxidative stress and anti-aging effect in Drosophila of royal jelly-collagen peptide.","authors":"Qiu, Wenjing; Chen, Xu; Tian, Yongqi; Wu, Daping; Du, Ming; Wang, Shaoyun","year":2020,"journal":"Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 135, 110881","doi":"10.1016/j.fct.2019.110881","pmid":"31622731","tags":["collagen-peptides","anti-aging","bioactive-food-peptides"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"ERJ-CP at 3 mg/mL extended natural aging Drosophila lifespan by 11.16%, upregulated antioxidant enzymes (T-SOD, GSH-Px, CAT), and reduced oxidative damage markers (MDA, PCO) while improving physical performance.","whyItMatters":"Dietary approaches to reducing oxidative damage and slowing aging are of broad consumer interest. This study provides early evidence for a food-derived peptide combination with anti-aging potential.","specificNumbers":"11.16% lifespan extension; hemolysis reduced from 56.35% to 18.78%; boosted SOD, GSH-Px, CAT; reduced MDA and PCO","methodology":"In vitro antioxidant assays followed by in vivo Drosophila (fruit fly) studies. Tested ERJ-CP effects on lifespan under oxidative stress (H2O2, paraquat) and natural aging. Measured antioxidant enzymes, oxidative damage markers, food intake, weight, and exercise capacity.","limitations":"Drosophila model — results may not translate to mammals or humans. Mechanism beyond antioxidant activity not explored. Optimal dosing for larger organisms unknown. No comparison to established anti-aging interventions."},{"rthcId":"RPEP-05083","title":"A long-acting isomer of Ac-SDKP attenuates pulmonary fibrosis through SRPK1-mediated PI3K/AKT and Smad2 pathway inhibition.","authors":"Qiu, Yueyuan; Wang, Zhaowei; Zhang, Xutao; Huang, Ping; Zhang, Wangqian; Zhang, Kuo; Wang, Shuning; He, Lei; Guo, Yanhai; Xiang, An; Zhang, Cun; Hao, Qiang; Li, Meng; Li, Weina; Zhang, Yingqi","year":2020,"journal":"IUBMB life, 72(12), 2611-2626","doi":"10.1002/iub.2389","pmid":"33135306","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05084","title":"The Effect of Thymosin beta4 on the Survival of Autologous Fat Grafting: A Preliminary Study.","authors":"Qu, Yaping; Wang, Qian; Fu, Su; Guo, Xiaoshuang; Luan, Jie; Mu, Dali","year":2020,"journal":"Aesthetic surgery journal, 40(9), NP519-NP529","doi":"10.1093/asj/sjaa062","pmid":"32144415","tags":["thymosin-beta-4","wound-healing"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Tβ4-treated fat grafts showed superior volume retention, weight preservation, adipocyte viability, tissue integrity, and angiogenesis at 2, 4, and 12 weeks compared to controls, with enhanced microcirculation confirmed by DCE-MRI.","whyItMatters":"Fat grafting is widely used in reconstructive and cosmetic surgery but has unpredictable survival rates. A simple additive like Tβ4 could significantly improve outcomes without changing the surgical procedure.","specificNumbers":"5 and 10 mcg/mL Tb4; MRI at 2, 4, 12 weeks; better volume/weight retention, adipocyte viability, angiogenesis, microcirculation","methodology":"Rabbit ear fat grafting model with 3 randomized groups: 5 μg/mL Tβ4, 10 μg/mL Tβ4, and PBS control. MRI imaging at 2, 4, and 12 weeks. Histological analysis of adipose tissue integrity, viability, and angiogenesis at each time point.","limitations":"Preliminary rabbit study with small, unspecified group sizes. Rabbit ear fat grafting may not perfectly model human facial or body fat grafting. Long-term retention beyond 12 weeks not assessed."},{"rthcId":"RPEP-05085","title":"Immediate inhibition of spinal secretory phospholipase A2 prevents the pain and elevated spinal neuronal hyperexcitability and neuroimmune regulatory genes that develop with nerve root compression.","authors":"Quindlen-Hotek, Julia C; Kartha, Sonia; Winkelstein, Beth A","year":2020,"journal":"Neuroreport, 31(15), 1084-1089","doi":"10.1097/WNR.0000000000001520","pmid":"32881777","tags":["neuropeptides","pain","inflammation"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Immediate intrathecal sPLA2 inhibition after C7 nerve root compression prevented mechanical allodynia, attenuated dorsal horn hyperexcitability, restored normal neuronal classification, and reduced mGluR5, substance P, IL1α, and IL1β gene expression to sham levels.","whyItMatters":"Nerve root compression (as in herniated discs) causes persistent pain that is difficult to treat once established. Identifying a window for early intervention could prevent chronic pain development.","specificNumbers":"Allodynia prevented at day 1; dorsal horn hyperexcitability attenuated; mGluR5, substance P, IL1α, IL1β reduced to sham levels","methodology":"Rat model of C7 nerve root compression with immediate intrathecal administration of sPLA2 inhibitor (thioetheramide-phosphorylcholine). Three groups: injury + treatment, injury alone, sham. Assessed at day 1: behavioral sensitivity, spinal neuronal excitability via electrophysiology, and spinal gene expression for glutamate receptors/transporters, substance P, and pro-inflammatory cytokines.","limitations":"Only day 1 assessed — unknown if protection persists long-term. Immediate treatment at injury time is not realistic for most clinical scenarios. Rat model may not fully replicate human cervical radiculopathy."},{"rthcId":"RPEP-05086","title":"Lactoferrin-Derived Peptides as a Control Strategy against Skinborne Staphylococcal Biofilms.","authors":"Quintieri, Laura; Caputo, Leonardo; Monaci, Linda; Cavalluzzi, Maria Maddalena; Denora, Nunzio","year":2020,"journal":"Biomedicines, 8(9)","doi":"10.3390/biomedicines8090323","pmid":"32883023","tags":["antimicrobial-peptides","skin-repair","bioactive-food-peptides"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Bovine lactoferrin hydrolysate achieved a minimal biofilm inhibitory concentration (MIBC) of 2.5 mg/mL against most staphylococcal strains — 4-8x lower than the minimal inhibitory concentration for direct killing. Purified peptides LFcinB and LFampin showed even lower MIBCs.","whyItMatters":"Biofilm-forming staphylococci on skin cause body odor, infections in immunocompromised patients, and catheter/implant complications. Lactoferrin peptides could offer a natural, cosmetic-grade biofilm control strategy.","specificNumbers":"HLF MIC 10->20 mg/mL; MIBC 2.5 mg/mL; individual peptides effective at lower concentrations; high eradication by dipping/spraying","methodology":"In vitro testing of bovine lactoferrin hydrolysate and purified peptides (LFcinB, LFampin) against coagulase-negative and positive staphylococci. Measured MIC, MIBC, and biofilm eradication on glass surfaces via dipping and spraying applications.","limitations":"In vitro study on glass surfaces — skin conditions differ significantly. No human skin testing. The gap between MIC and MIBC may limit effectiveness against established infections. Stability in cosmetic formulations not tested."},{"rthcId":"RPEP-05087","title":"Diminished Systemic and Mycobacterial Antigen Specific Anti-microbial Peptide Responses in Low Body Mass Index-Latent Tuberculosis Co-morbidity.","authors":"Rajamanickam, Anuradha; Munisankar, Saravanan; Dolla, Chandra Kumar; Babu, Subash","year":2020,"journal":"Frontiers in cellular and infection microbiology, 10, 165","doi":"10.3389/fcimb.2020.00165","pmid":"32411614","tags":["antimicrobial-peptides","ll-37","immune-function","infection"],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"Low BMI individuals with latent TB had diminished systemic, baseline, and mycobacterial antigen-stimulated levels of HNP1-3, granulysin, HBD-2, and cathelicidin compared to normal BMI counterparts, with positive BMI-AMP correlations.","whyItMatters":"Tuberculosis kills over 1 million people yearly, disproportionately in malnourished populations. Understanding how low BMI impairs antimicrobial peptide defenses could lead to nutritional or peptide-based interventions to prevent TB activation.","specificNumbers":"4 AMPs significantly lower in LBMI: HNP1-3, granulysin, HBD-2, cathelicidin; positive correlation with BMI","methodology":"Observational study comparing systemic and antigen-stimulated antimicrobial peptide levels (HNP1-3, granulysin, HBD-2, LL-37) between LTBI individuals with low BMI versus normal BMI. Measured both circulating levels and immune cell responses to mycobacterial antigens.","limitations":"Observational — cannot prove causation between low AMP levels and TB progression risk. Sample size not specified. Other immune mechanisms differ between BMI groups. Nutritional interventions not tested."},{"rthcId":"RPEP-05088","title":"Cell-Penetrable Peptide-Conjugated FADD Induces Apoptosis and Regulates Inflammatory Signaling in Cancer Cells.","authors":"Ranjan, Kishu; Waghela, Bhargav N; Vaidya, Foram U; Pathak, Chandramani","year":2020,"journal":"International journal of molecular sciences, 21(18)","doi":"10.3390/ijms21186890","pmid":"32961826","tags":["cell-penetrating","cancer","inflammation"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"TAT-FADD entered cancer cells via caveolar endocytosis, assembled DISC to trigger apoptosis, suppressed NF-κB and downstream anti-apoptotic genes (Bcl2, cFLIPL, RIP1, cIAP2), and inhibited NLRP3 inflammasome priming and IL-1β secretion.","whyItMatters":"Cancer cells survive by turning off their death signals. Directly delivering a death-signaling protein bypasses cancer's evasion mechanisms and simultaneously targets inflammation that promotes tumor growth.","specificNumbers":"TAT-FADD triggered DISC assembly; suppressed Bcl2, cFLIPL, RIP1, cIAP2; blocked NF-kB and NLRP3; reduced IL-1β","methodology":"In vitro study: purified FADD protein chemically conjugated to TAT peptide. Tested internalization pathway, DISC assembly, apoptosis induction, NF-κB signaling, and NLRP3 inflammasome activity in cancer cell lines. Compared to conventional apoptosis inducers.","limitations":"In vitro only — no animal or human data. TAT-FADD stability, immunogenicity, and tumor specificity in vivo are unknown. Manufacturing conjugated protein-peptide therapeutics at scale is challenging."},{"rthcId":"RPEP-05089","title":"ProTECT-Prediction of T-Cell Epitopes for Cancer Therapy.","authors":"Rao, Arjun A; Madejska, Ada A; Pfeil, Jacob; Paten, Benedict; Salama, Sofie R; Haussler, David","year":2020,"journal":"Frontiers in immunology, 11, 483296","doi":"10.3389/fimmu.2020.483296","pmid":"33244314","tags":["cancer","peptide-design"],"studyType":"computational","evidenceStrength":"not-applicable","keyFinding":"ProTECT automates cancer neoepitope peptide identification from patient data, identifying recurrent neoepitopes from TMPRSS2-ERG fusions and SPOP mutations in prostate cancer.","whyItMatters":"Personalized cancer vaccines depend on identifying the right peptide targets. ProTECT makes this reproducible and scalable, potentially accelerating clinical adoption.","specificNumbers":"326 samples; <30 min per sample; identified TMPRSS2-ERG and SPOP neoepitopes; free/open-source","methodology":"Computational pipeline development with validation on 326 TCGA prostate adenocarcinoma samples. Includes alignment, HLA haplotyping, mutation calling, peptide:MHC prediction, and ranking.","limitations":"Computational predictions require experimental validation. Predicted neoepitopes may not be immunogenic in vivo."},{"rthcId":"RPEP-05090","title":"Antinflammatory, antioxidant, and behavioral effects induced by administration of growth hormone-releasing hormone analogs in mice.","authors":"Recinella, Lucia; Chiavaroli, Annalisa; Orlando, Giustino; Ferrante, Claudio; Marconi, Guya Diletta; Gesmundo, Iacopo; Granata, Riccarda; Cai, Renzhi; Sha, Wei; Schally, Andrew V; Brunetti, Luigi; Leone, Sheila","year":2020,"journal":"Scientific reports, 10(1), 732","doi":"10.1038/s41598-019-57292-z","pmid":"31959947","tags":["hormone-optimization","anxiety-mood","inflammation","neuroprotection"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Both MIA-690 (antagonist) and MR-409 (agonist) produced anxiolytic and antidepressant-like effects, increased monoamine neurotransmitters, decreased NF-κB/TNF-α/IL-6, and increased Nrf2 expression in mouse prefrontal cortex, with MIA-690 showing higher anti-inflammatory efficacy.","whyItMatters":"GHRH analogues were developed as anti-cancer agents, but these brain effects suggest they could have unexpected therapeutic potential for neuropsychiatric conditions involving inflammation and oxidative stress.","specificNumbers":"5 mcg/day for 4 weeks; increased NE and serotonin; decreased NF-kB, TNF-α, IL-6; increased Nrf2; MIA-690 stronger anti-inflammatory","methodology":"Ex vivo: tested both compounds on LPS-treated mouse prefrontal cortex specimens for anti-inflammatory and antioxidant effects. In vivo: chronic treatment of mice followed by behavioral testing for anxiety and depression, with brain tissue analysis for neurotransmitters, inflammatory markers, and gene expression.","limitations":"Mouse study — behavioral tests may not translate to human psychiatric conditions. Mechanism of anxiolytic/antidepressant action not fully defined. Surprising that both agonist and antagonist produce similar behavioral effects. Sample sizes not reported."},{"rthcId":"RPEP-05091","title":"Host-Guest-Mediated Epitope Presentation on Self-Assembled Peptide Amphiphile Hydrogels.","authors":"Redondo-Gómez, Carlos; Padilla-Lopategui, Soraya; Azevedo, Helena S; Mata, Alvaro","year":2020,"journal":"ACS biomaterials science & engineering, 6(9), 4870-4880","doi":"10.1021/acsbiomaterials.0c00549","pmid":"33455284","tags":["peptide-delivery","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"The adamantane/β-cyclodextrin host-guest pair successfully anchored RGDS epitopes onto peptide amphiphile hydrogels via noncovalent interactions, supporting fibroblast attachment, organization, and spreading while maintaining hydrogel structural properties.","whyItMatters":"Current tissue engineering scaffolds use permanent chemical bonds to attach bioactive signals, which does not mimic the dynamic nature of real tissue. Reversible host-guest chemistry could create more biologically relevant scaffolds.","specificNumbers":"Adamantane/β-cyclodextrin pair; RGDS peptide display; fibroblasts attached, organized, and spread","methodology":"Designed peptide amphiphile hydrogels incorporating β-cyclodextrin hosts. Attached adamantane-modified RGDS peptides via host-guest interactions. Characterized hydrogel morphology (TEM) and rheology. Evaluated fibroblast attachment, organization, and spreading on scaffolds.","limitations":"In vitro proof of concept only. Only RGDS tested as a bioactive signal. Fibroblast behavior was the only cell type assessed. Long-term stability and in vivo performance unknown."},{"rthcId":"RPEP-05092","title":"Structural characterization, erythrocyte protection, and antifatigue effect of antioxidant collagen peptides from tilapia (Oreochromis nilotica L.) skin.","authors":"Ren, Yao; Wu, Hui; Chi, Yuanlong; Deng, Ruijie; He, Qiang","year":2020,"journal":"Food & function, 11(11), 10149-10160","doi":"10.1039/d0fo01803a","pmid":"33155595","tags":["collagen-peptides","bioactive-food-peptides","anti-aging"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"TSCP at 1 mg/mL reduced AAPH-induced hemolysis from 56.35% to 18.78% (p<0.01). At 2.5 mg/10g/day oral dosing, TSCP prolonged exhaustive swimming time while decreasing serum lactic acid, urea nitrogen, and creatine kinase, and increasing glycogen and SOD.","whyItMatters":"Tilapia skin is an abundant food processing byproduct. Converting it into functional antioxidant and anti-fatigue supplements adds value while addressing demand for natural performance nutrition products.","specificNumbers":"Collagen yield 22.6%; hemolysis reduced 56.35% → 18.78%; 5 peptides identified; octapeptide KPFGSGAT strongest; DH 52.7%/45.2%","methodology":"Prepared collagen hydrolysate from tilapia skin. Tested antioxidant activity via AAPH-induced erythrocyte hemolysis assay. In vivo anti-fatigue testing in mice using loaded swimming to exhaustion. Identified and synthesized five specific peptides from the active fraction.","limitations":"Mouse study — anti-fatigue effects in humans may differ. Specific peptide contributions to overall activity not fully parsed. Bioavailability after oral ingestion not confirmed. No human exercise performance data."},{"rthcId":"RPEP-05093","title":"Thymosin α1 protects from CTLA-4 intestinal immunopathology.","authors":"Renga, Giorgia; Bellet, Marina M; Pariano, Marilena; Gargaro, Marco; Stincardini, Claudia; D'Onofrio, Fiorella; Mosci, Paolo; Brancorsini, Stefano; Bartoli, Andrea; Goldstein, Allan L; Garaci, Enrico; Romani, Luigina; Costantini, Claudio","year":2020,"journal":"Life science alliance, 3(10)","doi":"10.26508/lsa.202000662","pmid":"32817121","tags":["thymosin-alpha-1","cancer","immune-function","gut-healing"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Tα1 prevented CTLA-4 inhibitor-induced intestinal immunopathology via IDO1-dependent tolerogenic pathways in the gut, while modulating tumor-infiltrating T cells to increase the CD8+/Treg ratio through context-dependent mechanisms.","whyItMatters":"Colitis is one of the most common and dose-limiting side effects of checkpoint immunotherapy. A compound that protects the gut without weakening anti-tumor immunity could allow more aggressive and effective cancer treatment.","specificNumbers":"IDO1 activated in gut, not in tumor; CD8+/Treg ratio inverted in tumors; modulated DC differentiation and chemokines","methodology":"Murine model of immune checkpoint inhibitor-induced colitis. Treated with thymosin alpha-1 alongside anti-CTLA-4 therapy. Evaluated gut pathology, IDO1 expression, tumor immune infiltrates, T-cell subsets, dendritic cell differentiation, and chemokine profiles.","limitations":"Mouse model only — human checkpoint inhibitor colitis may differ. Mechanism of context-dependent Tα1 activity (tolerogenic in gut, immunostimulatory at tumor) needs further elucidation. Long-term effects not assessed."},{"rthcId":"RPEP-05094","title":"ABC Transporter DerAB of Lactobacillus casei Mediates Resistance against Insect-Derived Defensins.","authors":"Revilla-Guarinos, Ainhoa; Zhang, Qian; Loderer, Christoph; Alcántara, Cristina; Müller, Ariane; Rahnamaeian, Mohammad; Vilcinskas, Andreas; Gebhard, Susanne; Zúñiga, Manuel; Mascher, Thorsten","year":2020,"journal":"Applied and environmental microbiology, 86(14)","doi":"10.1128/AEM.00818-20","pmid":"32414796","tags":["antimicrobial-peptides","infection"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"DerAB specifically confers resistance against insect-derived cysteine-stabilized αβ defensins. Its absence paradoxically increases nisin resistance by relieving signaling interference on the PsdRSAB module, allowing hyperactivation of nisin defense.","whyItMatters":"Understanding how bacteria resist antimicrobial peptides is crucial for developing peptide-based antibiotics. The crosstalk between defense systems reveals unexpected complexity in bacterial AMP resistance.","specificNumbers":"DerAB specific for insect cysteine-stabilized αβ defensins; deletion increased nisin resistance via PsdRSAB/ApsRSAB hyperactivation; DerB-Psd interaction confirmed","methodology":"Generated DerAB mutant in L. casei BL23. Tested sensitivity against peptides from bacteria, fungi, insects, and humans. Measured expression of other AMP resistance genes. Bacterial two-hybrid studies in E. coli to assess protein-protein interactions between DerB and Psd system components.","limitations":"In vitro study in a single bacterial species. The biological significance of insect defensin resistance for L. casei ecology is unclear. Signaling interference model proposed but detailed mechanism not fully elucidated."},{"rthcId":"RPEP-05095","title":"Multicomponent Peptide Stapling as a Diversity-Driven Tool for the Development of Inhibitors of Protein-Protein Interactions.","authors":"Ricardo, Manuel G; Ali, Ameena M; Plewka, Jacek; Surmiak, Ewa; Labuzek, Beata; Neochoritis, Constantinos G; Atmaj, Jack; Skalniak, Lukasz; Zhang, Ran; Holak, Tad A; Groves, Matthew; Rivera, Daniel G; Dömling, Alexander","year":2020,"journal":"Angewandte Chemie (International ed. in English), 59(13), 5235-5241","doi":"10.1002/anie.201916257","pmid":"31944488","tags":["cyclic-peptides","cancer","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"MCR-based stapled peptides achieved potent dual antagonism of MDM2 and MDMX binding to p53, with crystal structures demonstrating direct staple-protein interactions that contribute to binding affinity.","whyItMatters":"MDM2 and MDMX both suppress p53, and dual inhibition is needed to fully reactivate this tumor suppressor. This versatile stapling method enables rapid generation of diverse, potent dual inhibitors.","specificNumbers":"Dual MDM2/MDMX antagonists; multiple cocrystal structures; Ugi multicomponent reaction stapling","methodology":"Multicomponent reaction (Ugi) peptide stapling with diversity generation at the cross-linker. Activity assessed by fluorescence polarization, microscale thermophoresis, and 2D NMR. Multiple co-crystal structures solved with MDM2.","limitations":"In vitro biochemical and structural studies only. No cell-based or animal data on anti-cancer activity. Pharmacokinetics, cell penetration, and in vivo stability not assessed."},{"rthcId":"RPEP-05096","title":"Host Defense Peptide RNase 7 Is Down-regulated in the Skin of Diabetic Patients with or without Chronic Ulcers, and its Expression is Altered with Metformin.","authors":"Rodríguez-Carlos, Adrian; Trujillo, Valentin; Gonzalez-Curiel, Irma; Marin-Luevano, Sara; Torres-Juarez, Flor; Santos-Mena, Alan; Rivas-Santiago, Cesar; Enciso-Moreno, Jose A; Zaga-Clavellina, Veronica; Rivas-Santiago, Bruno","year":2020,"journal":"Archives of medical research, 51(4), 327-335","doi":"10.1016/j.arcmed.2020.03.006","pmid":"32229156","tags":["antimicrobial-peptides","diabetes","skin-repair","wound-healing"],"studyType":"observational","evidenceStrength":"preliminary","keyFinding":"RNase 7 was significantly decreased in skin of diabetic patients with and without foot ulcers compared to healthy donors. Metformin reduced RNase 7 expression in keratinocytes in vitro, while calcitriol, phenyl butyrate, and L-isoleucine did not restore it.","whyItMatters":"Diabetic foot ulcers affect millions and can lead to amputation. If metformin — taken by most type 2 diabetics — further reduces skin antimicrobial defenses, this has major clinical implications for wound management.","specificNumbers":"4 defense peptides measured; RNase 7 decreased in both diabetic groups; metformin reduced RNase 7 in vitro","methodology":"Observational study with skin biopsies from three groups: DFU patients (Wagner grade 3), diabetic patients without ulcers, and healthy donors. qPCR and immunohistochemistry for RNase 7, cathelicidin, HBD-2, and psoriasin. In vitro keratinocyte stimulation with metformin, glyburide, insulin, calcitriol, phenyl butyrate, and L-isoleucine.","limitations":"Sample sizes not specified. In vitro metformin effect on keratinocytes may not reflect in vivo skin responses. Correlation between RNase 7 reduction and infection outcomes not established. Known inducers failed to restore expression."},{"rthcId":"RPEP-05097","title":"Coptis chinensis Franch Directly Inhibits Proteolytic Activation of Kallikrein 5 and Cathelicidin Associated with Rosacea in Epidermal Keratinocytes.","authors":"Roh, Kyung-Baeg; Ryu, De-Hun; Cho, Eunae; Weon, Jin Bae; Park, Deokhoon; Kweon, Dae-Hyuk; Jung, Eunsun","year":2020,"journal":"Molecules (Basel, Switzerland), 25(23)","doi":"10.3390/molecules25235556","pmid":"33256158","tags":["ll-37","skin-repair","inflammation"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Coptis chinensis downregulated KLK5 and cathelicidin expression, inhibited KLK5 protease activity (reducing LL-37 processing), decreased pro-inflammatory cytokines, blocked TLR2/chitin signaling, and inhibited LL-37-induced endothelial cell proliferation.","whyItMatters":"Rosacea affects millions and current treatments are limited. Understanding how a traditional remedy targets the specific LL-37/KLK5 pathway behind rosacea could lead to more effective, mechanism-based treatments.","specificNumbers":"Reduced KLK5 expression and activity; reduced cathelicidin and LL-37 processing; blocked TLR2 from Demodex chitin; inhibited endothelial proliferation","methodology":"In vitro study using human epidermal keratinocytes and microvascular endothelial cells. Tested CC effects on KLK5/cathelicidin expression and activity, LL-37 processing, inflammatory cytokine production, TLR2 signaling (chitin stimulation), and endothelial proliferation.","limitations":"In vitro only — no clinical trial data. Herb extract composition may vary; active compounds not isolated. Bioavailability after topical application unknown. Single keratinocyte cell line used."},{"rthcId":"RPEP-05098","title":"Stress-related endogenous neuropeptides induce neuronal excitation in the Laterodorsal Tegmentum.","authors":"Romero-Leguizamón, Cesar R; Kohlmeier, Kristi A","year":2020,"journal":"European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 38, 86-97","doi":"10.1016/j.euroneuro.2020.07.008","pmid":"32768153","tags":["neuropeptides","anxiety-mood"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Urocortin and CRF produce pre- and postsynaptic excitatory effects on LDT cholinergic neurons through CRFR1 receptors, recruiting MAPK/ERK and SERCA-ATPase pathways.","whyItMatters":"This provides a cellular mechanism for how chronic stress could lead to psychiatric disorders through sustained excitation of cholinergic neurons controlling mood and reward circuits.","specificNumbers":"CRF and Ucn1 both excited via CRFR1; postsynaptic excitatory currents; enhanced synaptic events; Ca2+ rises; MAPK/ERK and SERCA pathways","methodology":"Patch clamp electrophysiology on immunohistochemically identified LDT neurons in brain slices, with concurrent calcium imaging.","limitations":"In vitro brain slice recordings may not reflect in vivo conditions. Mouse data may not translate to human brain. No behavioral validation."},{"rthcId":"RPEP-05099","title":"The GPCR accessory protein MRAP2 regulates both biased signaling and constitutive activity of the ghrelin receptor GHSR1a.","authors":"Rouault, Alix A J; Rosselli-Murai, Luciana K; Hernandez, Ciria C; Gimenez, Luis E; Tall, Gregory G; Sebag, Julien A","year":2020,"journal":"Science signaling, 13(613)","doi":"10.1126/scisignal.aax4569","pmid":"31911434","tags":["ghrp","receptor-signaling","weight-loss"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"MRAP2 inhibited GHSR1a constitutive activity, enhanced Gαq-dependent signaling, and blocked β-arrestin recruitment/signaling in response to ghrelin, with the Gαq and β-arrestin effects mediated by distinct MRAP2 regions.","whyItMatters":"GHSR1a is a major drug target for obesity. Understanding how MRAP2 biases its signaling could explain individual differences in ghrelin sensitivity and guide development of more selective anti-obesity drugs.","specificNumbers":"MRAP2 inhibited constitutive activity; enhanced Gq signaling; blocked β-arrestin; effects involved distinct MRAP2 regions","methodology":"In vitro signaling studies measuring GHSR1a constitutive activity, Gαq-dependent signaling, and β-arrestin recruitment in the presence and absence of MRAP2 and its domain variants. Assessed in response to endogenous agonist ghrelin.","limitations":"In vitro study — MRAP2 effects on ghrelin signaling in vivo may differ. Co-expression levels and tissue-specific factors not replicated. Functional consequences for food intake and glucose homeostasis not tested."},{"rthcId":"RPEP-05100","title":"Incretin-based drugs and risk of lung cancer among individuals with type 2 diabetes.","authors":"Rouette, J; Yin, H; Yu, O H Y; Bouganim, N; Platt, R W; Azoulay, L","year":2020,"journal":"Diabetic medicine : a journal of the British Diabetic Association, 37(5), 868-875","doi":"10.1111/dme.14287","pmid":"32124472","tags":["glp-1","cancer","peptide-safety","diabetes"],"studyType":"cohort","evidenceStrength":"strong","keyFinding":"Neither DPP-4 inhibitors (HR 1.07, 95% CI 0.87-1.32) nor GLP-1 receptor agonists (HR 1.02, 95% CI 0.68-1.54) were associated with increased lung cancer risk, with no duration-response relationship.","whyItMatters":"Safety concerns about cancer risk from newer diabetes medications need rigorous evaluation. This large study provides reassurance that incretin-based drugs do not increase lung cancer risk.","specificNumbers":"130,340 patients; 790 lung cancers; median 4.6 yr follow-up; DPP-4i HR 1.07 (0.87-1.32); GLP-1 RA HR 1.02 (0.68-1.54)","methodology":"Population-based cohort study using UK CPRD. 130,340 individuals newly treated with antidiabetes drugs (2007-2017), followed until 2018. Time-varying Cox proportional hazards models comparing incretin drugs to other second/third-line diabetes drugs. Assessed cumulative duration and time since initiation.","limitations":"Observational — cannot prove causation. Median 4.6-year follow-up may be insufficient for cancers with long latency. Residual confounding possible. GLP-1 agonist subgroup relatively small (wide confidence intervals)."},{"rthcId":"RPEP-05101","title":"Cell-Penetrating Peptides Escape the Endosome by Inducing Vesicle Budding and Collapse.","authors":"Sahni, Ashweta; Qian, Ziqing; Pei, Dehua","year":2020,"journal":"ACS chemical biology, 15(9), 2485-2492","doi":"10.1021/acschembio.0c00478","pmid":"32786250","tags":["cell-penetrating","peptide-delivery"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"CPPs escape endosomes through a budding-and-collapse mechanism: CPP-enriched vesicles bud from the endosomal membrane and subsequently collapse, releasing cargo into the cytosol.","whyItMatters":"Endosomal escape is the bottleneck for intracellular drug delivery — most cargo gets trapped and degraded. Understanding this mechanism enables rational design of more efficient CPPs and delivery vehicles.","specificNumbers":"CPPs concentrate at endosomal patches; budding creates CPP-enriched vesicles; collapse releases contents","methodology":"In vitro studies characterizing CPP endosomal escape mechanisms, identifying vesicle budding and collapse as the primary exit pathway. Detailed imaging and mechanistic analysis of CPP behavior on endosomal membranes.","limitations":"In vitro study — endosomal escape dynamics may differ in various cell types and in vivo. The budding-collapse mechanism may not apply to all CPPs. Quantitative escape efficiency not reported."},{"rthcId":"RPEP-05102","title":"Effect of Vesicle Size on the Cytolysis of Cell-Penetrating Peptides (CPPs).","authors":"Sakamoto, Kazutami; Kitano, Takeshi; Kuwahara, Haruka; Tedani, Megumi; Aburai, Kenichi; Futaki, Shiroh; Abe, Masahiko; Sakai, Hideki; Ohtaka, Hiroyasu; Yamashita, Yuji","year":2020,"journal":"International journal of molecular sciences, 21(19)","doi":"10.3390/ijms21197405","pmid":"33036492","tags":["cell-penetrating","peptide-delivery","bioavailability"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Smaller vesicles suppressed CPP cytolysis despite higher membrane curvature, because reduced lipid mobility in smaller vesicles restricts the local phase transitions required for CPP membrane penetration.","whyItMatters":"Understanding what controls CPP membrane crossing is essential for designing effective drug delivery systems. This study reveals lipid mobility as a key parameter, changing how we think about optimizing CPP-based carriers.","specificNumbers":"Smaller vesicles suppressed CPP entry; lipid mobility is the key factor; osmotic pressure helps only with sufficient mobility","methodology":"In vitro model vesicle (liposome) studies varying vesicle diameter to control membrane curvature. Measured CPP cytolysis (membrane penetration) across different vesicle sizes. Analyzed relationship between lipid mobility, curvature, and CPP penetration.","limitations":"Model vesicle study — artificial membranes lack the protein and carbohydrate complexity of real cell membranes. Findings need validation in cell-based systems. Limited CPP sequences tested."},{"rthcId":"RPEP-05103","title":"Key Process and Factors Controlling the Direct Translocation of Cell-Penetrating Peptide through Bio-Membrane.","authors":"Sakamoto, Kazutami; Morishita, Taku; Aburai, Kenichi; Sakai, Kenichi; Abe, Masahiko; Nakase, Ikuhiko; Futaki, Shiroh; Sakai, Hideki","year":2020,"journal":"International journal of molecular sciences, 21(15)","doi":"10.3390/ijms21155466","pmid":"32751745","tags":["cell-penetrating","peptide-delivery","bioavailability"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"CPP cytolysis occurs in two steps: rapid adsorption (saturated within 10 min) followed by linear-rate internalization dependent on osmotic pressure. The mechanism involves Lα to Mesh1 lipid phase transition creating punctured bilayer morphologies.","whyItMatters":"Precisely understanding each step and factor controlling CPP membrane crossing enables rational optimization of peptide-based drug delivery systems.","specificNumbers":"Adsorption saturates in 10 min; internalization linear; rate depends on osmotic pressure, temperature, lipid composition, electrolytes; Lα→Mesh1 transition","methodology":"Used giant unilamellar vesicles (GUVs) with trypsin digestion to separate and quantify CPP adsorption versus internalization. Time-course analysis with geometric calculations. Tested effects of osmotic pressure, temperature, lipid composition, and electrolyte environment.","limitations":"Model vesicle system — lacks membrane proteins and cytoskeletal interactions of real cells. Single CPP type likely tested. Quantitative parameters may not directly translate to cellular systems."},{"rthcId":"RPEP-05104","title":"The Antimicrobial Cathelicidin CRAMP Augments Platelet Activation during Psoriasis in Mice.","authors":"Salamah, Maryam F; Vallance, Thomas M; Kodji, Xenia; Ravishankar, Divyashree; Williams, Harry F; Brain, Susan D; Vaiyapuri, Sakthivel","year":2020,"journal":"Biomolecules, 10(9)","doi":"10.3390/biom10091267","pmid":"32887440","tags":["ll-37","inflammation","cardiovascular"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"mCRAMP levels were elevated in psoriatic mouse skin and plasma. Psoriatic plasma augmented platelet activation in healthy mouse platelets. The effect was partially mediated through Fpr2/3 (FPR2/ALX), as receptor inhibition or knockout significantly reduced platelet activation.","whyItMatters":"Cardiovascular complications are a major cause of morbidity in psoriasis and other inflammatory diseases. Identifying cathelicidin-FPR2/ALX as a driver of platelet activation reveals a potential therapeutic target.","specificNumbers":"Elevated fibrinogen binding, P-selectin, soluble P-selectin, and CRAMP in psoriasis; partial inhibition by WRW4 and Fpr2/3 deficiency","methodology":"Imiquimod-induced psoriasis mouse model. Measured platelet activation markers (fibrinogen binding, P-selectin), plasma and skin mCRAMP levels, and soluble P-selectin. Used FPR2/ALX inhibitors (WRW4) and Fpr2/3-deficient mice to validate receptor involvement.","limitations":"Mouse model — mCRAMP and LL-37 are not identical. Psoriasis model (imiquimod) may not fully replicate human disease. FPR2/ALX blockade only partially reduced activation, suggesting other mechanisms. Clinical relevance in human psoriasis not validated."},{"rthcId":"RPEP-05105","title":"Brain and kidney GHS-R1a underexpression is associated with changes in renal function and hemodynamics during neurogenic hypertension.","authors":"Sales da Silva, Elder; Ferreira, Patrícia Maria; Castro, Carlos Henrique; Pacheco, Lilian Fernanda; Graziani, Daniel; Pontes, Carolina Nobre Ribeiro; Bessa, Amanda de Sá Martins de; Fernandes, Erika; Naves, Lara Marques; Ribeiro, Larissa Cristina Dos Santos; Mendonça, Michelle Mendanha; Gomes, Rodrigo Mello; Pedrino, Gustavo Rodrigues; Ferreira, Reginaldo Nassar; Xavier, Carlos Henrique","year":2020,"journal":"Molecular and cellular endocrinology, 518, 110984","doi":"10.1016/j.mce.2020.110984","pmid":"32814069","tags":["mk-677","ghrp","cardiovascular","kidney","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"GHS-R1a protein was decreased in brain areas and kidneys of hypertensive rats. Ghrelin reduced arterial pressure and increased renal artery conductance in SHR. GHS-R1a antagonism altered renal electrolyte handling in normal but not hypertensive rats, suggesting impaired receptor function in hypertension.","whyItMatters":"Hypertension is the leading cause of kidney disease and cardiovascular death. If ghrelin receptor downregulation contributes to hypertensive kidney damage, it could represent a new therapeutic target.","specificNumbers":"GHS-R1a reduced in brain and kidneys of SHR; ghrelin reduced BP and increased renal artery conductance in SHR; MK-677 changed osmolarity parameters","methodology":"Compared Wistar (normal) and SHR (hypertensive) rats. Systemically injected ghrelin, MK-677, GHS-R1a antagonist PF04628935, or combinations. Metabolic cage studies measuring urine output and electrolytes. Assessed renal hemodynamics and vasomotion. Western blot for GHS-R1a levels in brain, aorta, renal artery, renal cortex, and medulla.","limitations":"Animal model of genetic hypertension — may not reflect human essential hypertension. Ghrelin receptor levels measured at a single time point. Causal relationship between receptor downregulation and hypertension not established."},{"rthcId":"RPEP-05106","title":"Marine collagen and its derivatives: Versatile and sustainable bio-resources for healthcare.","authors":"Salvatore, Luca; Gallo, Nunzia; Natali, Maria Lucia; Campa, Lorena; Lunetti, Paola; Madaghiele, Marta; Blasi, Federica Stella; Corallo, Angelo; Capobianco, Loredana; Sannino, Alessandro","year":2020,"journal":"Materials science & engineering. C, Materials for biological applications, 113, 110963","doi":"10.1016/j.msec.2020.110963","pmid":"32487384","tags":["collagen-peptides","bioactive-food-peptides","wound-healing","skin-repair"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Marine collagen and its derivatives (gelatin, peptides) show versatile bioactive properties including potential for tissue engineering, wound healing, dietary supplementation for weight management and glycemic control, with growing preclinical and clinical evidence.","whyItMatters":"Marine collagen converts polluting fish waste into high-value healthcare products while avoiding the disease transmission and religious/cultural concerns associated with mammalian (bovine/porcine) collagen.","specificNumbers":"Sources: fish skin and scales; applications in tissue engineering, supplements, cosmetics; bioactive: antioxidant, glycemic control, weight management","methodology":"Comprehensive literature review covering marine collagen extraction, physicochemical properties, healthcare applications (food, medicine, pharmaceutics, cosmetics), preclinical and clinical evidence, and market analysis.","limitations":"Review format — no new data. Marine collagen has lower denaturation temperature than mammalian collagen, limiting some applications. Many bioactive claims remain at preclinical stages. Product standardization challenges exist."},{"rthcId":"RPEP-05107","title":"The structure of the antimicrobial human cathelicidin LL-37 shows oligomerization and channel formation in the presence of membrane mimics.","authors":"Sancho-Vaello, Enea; Gil-Carton, David; François, Patrice; Bonetti, Eve-Julie; Kreir, Mohamed; Pothula, Karunakar Reddy; Kleinekathöfer, Ulrich; Zeth, Kornelius","year":2020,"journal":"Scientific reports, 10(1), 17356","doi":"10.1038/s41598-020-74401-5","pmid":"33060695","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05108","title":"Synthetic Peptide Libraries: From Random Mixtures to In Vivo Testing.","authors":"Sandomenico, Annamaria; Caporale, Andrea; Doti, Nunzianna; Cross, Simon; Cruciani, Gabriele; Chambery, Angela; De Falco, Sandro; Ruvo, Menotti","year":2020,"journal":"Current medicinal chemistry, 27(6), 997-1016","doi":"10.2174/0929867325666180716110833","pmid":"30009695","tags":["peptide-design"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Synthetic peptide libraries have generated bioactive compounds with potencies from sub-nanomolar to micromolar over 25 years, with recent computational and engineering advances enabling more targeted library designs including focused tripeptide collections against druggable cavities.","whyItMatters":"Drug discovery needs efficient methods to explore chemical space. Peptide libraries bridge the gap between biologics and small molecules, offering a systematic approach to finding potent, specific bioactive compounds.","specificNumbers":"25 years of use; potencies sub-nM to µM; compounds reaching in vivo testing; new focused tripeptide library approach proposed","methodology":"Literature review covering methodologies for combinatorial peptide library preparation and screening, focusing on case studies where discovered compounds advanced to in vivo testing. Introduces a new approach for focused tripeptide library design.","limitations":"Review format — surveys existing work without new data. Many library-derived compounds remain at preclinical stages. The proposed tripeptide library approach is introduced but not yet fully validated."},{"rthcId":"RPEP-05109","title":"Dietary protein modulates digestive enzyme activities and gene expression in red tilapia juveniles.","authors":"Santos, W M; Costa, L S; López-Olmeda, J F; Costa, N C S; Santos, F A C; Oliveira, C G; Guilherme, H O; Bahiense, R N; Luz, R K; Ribeiro, P A P","year":2020,"journal":"Animal : an international journal of animal bioscience, 14(9), 1802-1810","doi":"10.1017/S1751731120000543","pmid":"32213230","tags":["neuropeptides","bioactive-food-peptides"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"The 30% CP diet optimized growth, while 42% CP decreased ghrelin and insulin expression, increased CCK and peptide YY expression, and reduced growth performance compared to moderate protein levels.","whyItMatters":"Understanding how dietary protein affects appetite hormones in fish has dual value: optimizing aquaculture feeding and demonstrating conserved peptide hormone mechanisms across vertebrates.","specificNumbers":"240 fish; 4 diets (24-42% CP); 42 days; 30% optimal; 42% decreased ghrelin/insulin, increased CCK/PYY","methodology":"240 red tilapia juveniles across 20 tanks fed four isoenergetic diets (24%, 30%, 36%, 42% crude protein) for 42 days. Measured growth performance, protein retention, body composition, protease activity, and gene expression for digestive enzymes and appetite-regulating hormones.","limitations":"Fish study — appetite regulation mechanisms may not directly apply to human protein intake recommendations. Only one fish species tested. Gene expression measured but not circulating hormone levels."},{"rthcId":"RPEP-05110","title":"Relationships among pulmonary capillary wedge pressure, dry weight and natriuretic peptide in patients undergoing hemodialysis: a three-dimensional speckle tracking echocardiography study.","authors":"Sato, Hidemaro; Kawasaki, Masanori; Tanaka, Ryuhei; Yoshizane, Takashi; Ono, Koji; Tadokoro, Mitsunobu; Yano, Yoko; Kondou, Takehito; Kariya, Tatsuya; Nagata, Kijun; Gotoh, Koshi; Sawada, Shigeki; Noda, Toshiyuki; Watanabe, Sachiro","year":2020,"journal":"Journal of echocardiography, 18(3), 160-168","doi":"10.1007/s12574-020-00461-1","pmid":"31997088","tags":["natriuretic-peptides","cardiovascular","kidney"],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"ePCWP changes during HD correlated strongly with body weight changes (r=0.814, p<0.05) and with ANP changes (r=0.523), but not with BNP changes (p=0.47), making ePCWP the most sensitive real-time fluid status marker.","whyItMatters":"Accurate fluid management during dialysis is critical — too much fluid removal causes dangerous drops in blood pressure, while too little leads to fluid overload. Real-time monitoring could optimize dialysis sessions.","specificNumbers":"81 patients; ePCWP vs BW r=0.814; ePCWP vs ln ANP r=0.523; ePCWP vs ln BNP not significant (p=0.47)","methodology":"Observational study measuring ePCWP by 3D speckle-tracking echocardiography and body weight in 81 HD patients before and after dialysis. ANP and BNP measured by blood tests in 31 patients. Correlation analysis between ePCWP, body weight, and natriuretic peptide changes.","limitations":"Moderate sample size (31 for peptide analysis). Single-center study during sinus rhythm only. ePCWP is an estimate, not direct measurement. Operator dependency of echocardiography. BW change assumed to equal fluid removal."},{"rthcId":"RPEP-05111","title":"Collagen-Derived Di-Peptide, Prolylhydroxyproline (Pro-Hyp): A New Low Molecular Weight Growth-Initiating Factor for Specific Fibroblasts Associated With Wound Healing.","authors":"Sato, Kenji; Asai, Tomoko T; Jimi, Shiro","year":2020,"journal":"Frontiers in cell and developmental biology, 8, 548975","doi":"10.3389/fcell.2020.548975","pmid":"33330443","tags":["collagen-peptides","wound-healing","oral-peptides"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Pro-Hyp is a low molecular weight growth-initiating factor that selectively triggers proliferation of p75NTR-positive (stem cell-like) fibroblasts on collagen gel but not p75NTR-negative fibroblasts. Oral collagen/gelatin delivers Pro-Hyp to tissues and accelerates wound healing in animals and humans.","whyItMatters":"This provides a molecular explanation for why collagen supplements help wounds heal — a connection that was observed clinically but not mechanistically understood. It also identifies Pro-Hyp as a targetable factor for chronic wound therapy.","specificNumbers":"Pro-Hyp dipeptide; selective for p75NTR+ fibroblasts on collagen; oral bioavailability confirmed; improves pressure ulcers and diabetic wounds","methodology":"Review integrating cell biology studies of fibroblast heterogeneity, Pro-Hyp signaling on collagen substrates, and preclinical/clinical evidence for oral collagen supplementation in wound healing.","limitations":"Review — summarizes existing evidence without new data. The p75NTR selectivity mechanism needs further elucidation. Optimal Pro-Hyp doses for clinical wound healing not standardized."},{"rthcId":"RPEP-05112","title":"Improving antibody-based therapies by chemical engineering of antibodies with multimeric cell-penetrating peptides for elevated intracellular delivery.","authors":"Sauter, Max; Strieker, Matthias; Kleist, Christian; Wischnjow, Artjom; Daniel, Volker; Altmann, Annette; Haberkorn, Uwe; Mier, Walter","year":2020,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 322, 200-208","doi":"10.1016/j.jconrel.2020.03.005","pmid":"32184098","tags":["cell-penetrating","cancer","peptide-delivery"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"tCPP conjugation achieved up to 4-fold elevated internalization rates for three clinical antibodies while retaining target specificity. tCPP-Kadcyla showed 6-fold increased cytotoxicity. Favorable pharmacokinetics limited off-target accumulation.","whyItMatters":"Many antibody-drug conjugates underperform because they do not efficiently enter cancer cells. Boosting internalization with CPPs could make existing ADCs significantly more effective without developing entirely new drugs.","specificNumbers":"4x internalization; 6x cytotoxicity for Kadcyla-tCPP; maintained specificity; improved PK; 3 antibodies tested","methodology":"Solid-phase synthesis of tetrameric CPPs (tCPPs) conjugated to matuzumab, trastuzumab, and Kadcyla. Measured internalization rates, target specificity, pharmacokinetics, and cytotoxicity in cancer cell lines.","limitations":"In vitro only — in vivo efficacy and toxicity not assessed. Off-target effects of antigen-independent internalization need careful evaluation. Manufacturing scalability of tCPP-conjugated antibodies not addressed."},{"rthcId":"RPEP-05113","title":"Pancreatic Polypeptide but Not Other Members of the Neuropeptide Y Family Shows a Moderate Association With Perceived Anxiety in Obese Men.","authors":"Schaper, Selina Johanna; Hofmann, Tobias; Wölk, Ellen; Weibert, Elena; Rose, Matthias; Stengel, Andreas","year":2020,"journal":"Frontiers in human neuroscience, 14, 578578","doi":"10.3389/fnhum.2020.578578","pmid":"33192409","tags":["neuropeptides","anxiety-mood","weight-loss"],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"Pancreatic polypeptide (PP) plasma levels showed a moderate association with perceived anxiety specifically in obese men. NPY and PYY were not associated with anxiety, depressiveness, or perceived stress.","whyItMatters":"Obesity and anxiety commonly co-occur, but the biological link is poorly understood. PP's sex-specific association with anxiety suggests the gut-brain axis may contribute differently to mental health in obese men versus women.","specificNumbers":"144 patients; PP-anxiety r=0.41 p=0.007 in men; women had higher anxiety (8.13 vs 5.93) and stress (52.62 vs 41.23); no NPY/PYY mood associations","methodology":"Cross-sectional observational study in 144 obese patients. Measured plasma NPY, PYY, and PP levels. Assessed anxiety, depressiveness, and perceived stress using validated questionnaires. Analyzed associations with sex-stratified statistical models.","limitations":"Cross-sectional — cannot determine causation. Moderate sample size. Only obese participants — may not apply to normal weight. PP-anxiety association was moderate, not strong. Self-reported psychological measures."},{"rthcId":"RPEP-05114","title":"Adaptable antigen matrix platforms for peptide vaccination strategies and T cell-mediated anti-tumor immunity.","authors":"Schetters, Sjoerd T T; Li, R J Eveline; Kruijssen, Laura J W; Engels, Steef; Ambrosini, Martino; Garcia-Vallejo, Juan J; Kalay, Hakan; Unger, Wendy W J; van Kooyk, Yvette","year":2020,"journal":"Biomaterials, 262, 120342","doi":"10.1016/j.biomaterials.2020.120342","pmid":"32905903","tags":["cancer","peptide-design","immune-function"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Non-linear trimeric peptide vaccines enhanced dendritic cell antigen presentation to CD8+ T cells both in vitro and in vivo, generating KLRG1+ effector T cells capable of recognizing and killing antigen-expressing target cells.","whyItMatters":"Single peptide cancer vaccines often fail due to poor immunogenicity. Trimeric structures offer a simple chemical solution to boost immune responses without changing the antigen sequence itself.","specificNumbers":"Trimers > SLP for CD8+ and CD4+ responses; AMAX improved yield/purity/solubility; DC-SIGN targeting and CD40+MF59 synergistic; neoantigen AMAX reduced tumor growth","methodology":"Solid phase peptide synthesis of non-linear peptide trimers. In vitro dendritic cell-T cell co-culture. In vivo mouse vaccination with trimer versus monomer peptides. Assessed CD8+ T cell phenotype (KLRG1+), cytotoxicity, and anti-tumor responses.","limitations":"Mouse study — immune responses may differ in humans. Specific tumor protection data not detailed in abstract. Long-term immunity and memory T cell formation not assessed."},{"rthcId":"RPEP-05115","title":"A once-monthly GLP-1 receptor agonist for treatment of diabetic cats.","authors":"Schneider, E L; Reid, R; Parkes, D G; Lutz, T A; Ashley, G W; Santi, D V","year":2020,"journal":"Domestic animal endocrinology, 70, 106373","doi":"10.1016/j.domaniend.2019.07.001","pmid":"31479925","tags":["glp-1-receptor-agonists","drug-delivery-systems","diabetes"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"A hydrogel microsphere delivery system with a self-cleaving β-eliminative linker enables sustained release of exenatide from a single subcutaneous injection, providing once-monthly dosing for feline diabetes treatment.","whyItMatters":"Feline diabetes is common and typically requires twice-daily insulin injections. A once-monthly GLP-1 treatment could dramatically improve compliance and quality of life for both cats and their owners.","specificNumbers":"Bioavailability: 93% ([Gln28]exenatide) vs 52% (exenatide); depot half-life ~40 days vs ~40 min free peptide; dose 10 mcg/kg","methodology":"Developed hydrogel microspheres covalently attached to exenatide via β-eliminative linkers. Tested pharmacokinetics and glycemic effects after subcutaneous injection in diabetic cats.","limitations":"Small sample size. Preliminary pharmacokinetic and efficacy data. Long-term safety of repeated monthly injections not established. Cost comparison with insulin therapy not addressed."},{"rthcId":"RPEP-05116","title":"Monoclonal antibodies blocking CGRP transmission: An update on their added value in migraine prevention.","authors":"Schoenen, J; Manise, M; Nonis, R; Gérard, P; Timmermans, G","year":2020,"journal":"Revue neurologique, 176(10), 788-803","doi":"10.1016/j.neurol.2020.04.027","pmid":"32758365","tags":["cgrp","neuropeptides","migraine"],"studyType":"review","evidenceStrength":"strong","keyFinding":"CGRP/receptor-targeting monoclonal antibodies represent a paradigm shift from repurposed treatments to migraine-specific prevention, with strong clinical trial evidence supporting their efficacy and favorable safety profiles.","whyItMatters":"Migraine affects over 1 billion people worldwide and was previously treated with drugs designed for other conditions. These antibodies are the first treatments designed specifically for migraine biology.","specificNumbers":"50% responder rate advantage: 21.4% episodic, 17.4% chronic; NNT 4-5 episodic; 4 monoclonal antibodies reviewed","methodology":"Review of translational research history, clinical trial data, and clinical experience with CGRP-blocking monoclonal antibodies and gepants for migraine prevention.","limitations":"Review format. Long-term safety data still accumulating. Cost remains a barrier for many patients. Not all migraine patients respond to anti-CGRP therapy. Head-to-head comparisons between different antibodies are limited."},{"rthcId":"RPEP-05117","title":"Neuropeptide reporter assay for serum, capillary blood and blood cards.","authors":"Schreiber, U; Engl, C; Bayer, M; König, S","year":2020,"journal":"MethodsX, 7, 100985","doi":"10.1016/j.mex.2020.100985","pmid":"32685383","tags":["substance-p","bradykinin","biomarkers"],"studyType":"methods paper","evidenceStrength":"preliminary","keyFinding":"Substance P and bradykinin neuropeptide reporter assays were successfully adapted from serum to capillary blood and dried blood card formats, expanding their utility for inflammation and pain research.","whyItMatters":"Measuring protease activity is important for inflammation and pain research. Using finger-prick blood and dried blood cards instead of venous blood draws makes sample collection easier, especially in clinical settings or remote locations.","specificNumbers":"2 neuropeptide reporters; 3 sample types (serum, capillary blood, dried blood cards)","methodology":"Protocol development adapting existing serum-based neuropeptide protease assays (substance P and bradykinin) for use with capillary blood and dried blood card samples. Comparison with established serum protocols.","limitations":"Methods paper — demonstrates protocols without large-scale validation. Sensitivity differences between sample types need characterization. Clinical utility not yet established."},{"rthcId":"RPEP-05118","title":"Validation data for the use of bradykinin and substance P protease activity assays with capillary blood and blood cards.","authors":"Schreiber, Ulrich; Bayer, Malte; König, Simone","year":2020,"journal":"Data in brief, 28, 104873","doi":"10.1016/j.dib.2019.104873","pmid":"31872007","tags":["substance-p","bradykinin","biomarkers"],"studyType":"methods paper","evidenceStrength":"preliminary","keyFinding":"Validation data confirms bradykinin and substance P protease activity assays are reliable when using capillary blood and blood card samples, supporting the protocols described in the companion methods paper.","whyItMatters":"Validation data is essential for researchers adopting new assay formats. Without it, labs cannot confidently use the simplified sample collection methods for protease activity measurement.","specificNumbers":"2 assays validated for 2 alternative sample types","methodology":"Validation experiments comparing bradykinin and substance P protease assay performance across serum, capillary blood, and dried blood card sample types. Statistical analysis of precision, accuracy, and reproducibility.","limitations":"Data paper — focused on assay validation rather than clinical application. Limited to the specific neuropeptide substrates tested."},{"rthcId":"RPEP-05119","title":"Human Defensins: A Novel Approach in the Fight against Skin Colonizing Staphylococcus aureus.","authors":"Scudiero, Olga; Brancaccio, Mariarita; Mennitti, Cristina; Laneri, Sonia; Lombardo, Barbara; De Biasi, Margherita G; De Gregorio, Eliana; Pagliuca, Chiara; Colicchio, Roberta; Salvatore, Paola; Pero, Raffaela","year":2020,"journal":"Antibiotics (Basel, Switzerland), 9(4)","doi":"10.3390/antibiotics9040198","pmid":"32326312","tags":["defensins","antimicrobial-peptides","immune-function"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Human defensins play a critical role in skin defense against S. aureus but are countered by bacterial evasion mechanisms. Enhancing or supplementing defensin activity represents a potential novel approach to combat staph skin infections.","whyItMatters":"S. aureus skin infections — including antibiotic-resistant MRSA — are a growing public health problem. Defensin-based approaches could provide new treatments that are less susceptible to resistance development than traditional antibiotics.","specificNumbers":"Not applicable (narrative review)","methodology":"Literature review covering human defensin biology, their role in skin immunity against S. aureus, bacterial evasion mechanisms, and potential therapeutic applications.","limitations":"Review — no new experimental data. S. aureus evasion of defensins suggests that defensin-based therapeutics alone may face limitations. Clinical validation of defensin-based treatments is still early."},{"rthcId":"RPEP-05120","title":"Enhanced Efficacy of Photodynamic Therapy by Coupling a Cell-Penetrating Peptide with Methylene Blue.","authors":"Ser, Jinhui; Lee, Ji Yeon; Kim, Yong Ho; Cho, Hoonsung","year":2020,"journal":"International journal of nanomedicine, 15, 5803-5811","doi":"10.2147/IJN.S254881","pmid":"32821102","tags":["cell-penetrating-peptides","cancer-research","drug-delivery-systems"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"CPP-methylene blue conjugates showed enhanced cellular uptake, lysosomal localization, and improved photodynamic therapy efficacy against cancer cells compared to unconjugated methylene blue.","whyItMatters":"Photodynamic therapy is limited by poor photosensitizer uptake into cancer cells. CPP conjugation could overcome this barrier, making PDT a more effective cancer treatment option.","specificNumbers":"MB-Pro localized to lysosomes; induced necrosis vs apoptosis with MB alone","methodology":"Conjugated protamine CPP with methylene blue via chemical coupling, purified by FPLC. Tested cellular uptake, subcellular localization, and PDT efficacy in cancer cell lines in vitro.","limitations":"In vitro study only — no in vivo tumor PDT data. Light penetration limits PDT to superficial or accessible tumors. Selectivity for cancer over normal cells not fully characterized."},{"rthcId":"RPEP-05121","title":"Top-Down Proteomics of Human Saliva Discloses Significant Variations of the Protein Profile in Patients with Mastocytosis.","authors":"Serrao, Simone; Firinu, Davide; Olianas, Alessandra; Deidda, Margherita; Contini, Cristina; Iavarone, Federica; Sanna, M Teresa; Boroumand, Mozhgan; Amado, Francisco; Castagnola, Massimo; Messana, Irene; Del Giacco, Stefano; Manconi, Barbara; Cabras, Tiziana","year":2020,"journal":"Journal of proteome research, 19(8), 3238-3253","doi":"10.1021/acs.jproteome.0c00207","pmid":"32575983","tags":["thymosin-beta-4","defensins","biomarkers"],"studyType":"observational","evidenceStrength":"preliminary","keyFinding":"Salivary proteome analysis revealed significant variations in thymosin beta-4, defensins, and other proteins between mastocytosis subtypes (cutaneous, systemic with/without skin lesions) and healthy controls.","whyItMatters":"Mastocytosis diagnosis typically requires invasive bone marrow biopsy. Salivary biomarkers could offer a non-invasive alternative for classification and monitoring of this rare disease.","specificNumbers":"3 disease subtypes analyzed; down-regulated statherin, histatins, aPRPs; up-regulated antileukoproteinase, S100A8, thymosin beta-4","methodology":"Top-down proteomics with label-free quantitation of saliva from patients with cutaneous mastocytosis, systemic mastocytosis (with and without cutaneous lesions), and healthy controls.","limitations":"Small sample size typical for rare disease studies. Findings need validation in larger cohorts. Specificity of salivary changes to mastocytosis versus other inflammatory conditions not established."},{"rthcId":"RPEP-05122","title":"Co-delivery of Peptide Neoantigens and Stimulator of Interferon Genes Agonists Enhances Response to Cancer Vaccines.","authors":"Shae, Daniel; Baljon, Jessalyn J; Wehbe, Mohamed; Christov, Plamen P; Becker, Kyle W; Kumar, Amrendra; Suryadevara, Naveenchandra; Carson, Carcia S; Palmer, Christian R; Knight, Frances C; Joyce, Sebastian; Wilson, John T","year":2020,"journal":"ACS nano, 14(8), 9904-9916","doi":"10.1021/acsnano.0c02765","pmid":"32701257","tags":["cancer-research","drug-delivery-systems","immune-function"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Co-delivery of peptide neoantigens with STING agonists via nanoparticles enhanced neoantigen-specific CD8+ T cell responses and improved cancer vaccine efficacy, leveraging the STING pathway's role in tumor immune surveillance.","whyItMatters":"Personalized neoantigen vaccines have failed partly due to weak immunogenicity. STING agonist co-delivery could be the missing piece that makes these vaccines clinically effective, especially combined with checkpoint inhibitors.","specificNumbers":"Multiple tumor models; complete rejection in some mice; durable immune memory; combined with checkpoint blockade","methodology":"Nanoparticle formulation co-encapsulating peptide neoantigens and STING agonists. Tested immunogenicity and anti-tumor efficacy in mouse cancer models. Assessed CD8+ T cell priming, activation, and tumor responses.","limitations":"Small animal study — mouse immune responses may not predict human vaccine efficacy. Nanoparticle manufacturing scalability and cost not addressed. STING agonist side effects need evaluation."},{"rthcId":"RPEP-05123","title":"In vitro gastric emptying characteristics of konjac glucomannan with different viscosity and its effects on appetite regulation.","authors":"Shang, Longchen; Wang, Yi; Ren, Yanyan; Ai, Tingyang; Zhou, Peiyuan; Hu, Ling; Wang, Ling; Li, Jing; Li, Bin","year":2020,"journal":"Food & function, 11(9), 7596-7610","doi":"10.1039/d0fo01104e","pmid":"32869813","tags":["glp-1-receptor-agonists","ghrelin","appetite-regulation","gut-peptides"],"studyType":"randomized controlled trial","evidenceStrength":"moderate","keyFinding":"Higher viscosity konjac glucomannan delayed gastric emptying, increased GLP-1 and PYY secretion, and enhanced subjective satiety compared to lower viscosity or control conditions.","whyItMatters":"Konjac glucomannan is widely used as a dietary supplement for weight management. This study provides mechanistic evidence connecting its viscosity to specific appetite hormone responses and gastric motility effects.","specificNumbers":"n=22; hunger p=0.006; fullness p<0.001; desire-to-eat p=0.002; prospective consumption p=0.001; 5 hormones measured (insulin, GLP-1, PYY3-36, CCK-8, ghrelin)","methodology":"Combined in vitro gastric emptying simulation with a randomized controlled trial in humans. Measured rheological properties, gastric emptying, subjective appetite, glycemia, insulin, GLP-1, PYY, CCK, and ghrelin responses to different KGM viscosities.","limitations":"Small sample size. Short-term acute testing — chronic effects unknown. In vitro gastric simulator may not fully replicate in vivo digestion. KGM palatability at high viscosity may limit practical intake."},{"rthcId":"RPEP-05124","title":"Acyl-ghrelin Is Permissive for the Normal Counterregulatory Response to Insulin-Induced Hypoglycemia.","authors":"Shankar, Kripa; Gupta, Deepali; Mani, Bharath K; Findley, Brianna G; Lord, Caleb C; Osborne-Lawrence, Sherri; Metzger, Nathan P; Pietra, Claudio; Liu, Chen; Berglund, Eric D; Zigman, Jeffrey M","year":2020,"journal":"Diabetes, 69(2), 228-237","doi":"10.2337/db19-0438","pmid":"31685528","tags":["ghrelin","diabetes","blood-sugar-regulation"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"Ghrelin knockout mice showed impaired counterregulatory responses to insulin-induced hypoglycemia, demonstrating that acyl-ghrelin is permissive for normal blood sugar recovery during hypoglycemic episodes.","whyItMatters":"Hypoglycemia is a major risk for diabetic patients on insulin. Understanding ghrelin's role in blood sugar defense could lead to new strategies to prevent dangerous hypoglycemic episodes.","specificNumbers":"10-fold higher GIR in ghrelin-KO; blunted corticosterone and GH; HM01 reduced GIR and increased corticosterone and GH","methodology":"Used ghrelin knockout mice subjected to insulin-induced hypoglycemia. Measured counterregulatory hormone responses, blood glucose recovery, and compared to wild-type controls.","limitations":"Mouse study — knockout models may not perfectly predict human ghrelin deficiency. Small sample. Complete ghrelin absence is more extreme than natural variation in ghrelin levels."},{"rthcId":"RPEP-05125","title":"High-Throughput Prediction of MHC Class I and II Neoantigens with MHCnuggets.","authors":"Shao, Xiaoshan M; Bhattacharya, Rohit; Huang, Justin; Sivakumar, I K Ashok; Tokheim, Collin; Zheng, Lily; Hirsch, Dylan; Kaminow, Benjamin; Omdahl, Ashton; Bonsack, Maria; Riemer, Angelika B; Velculescu, Victor E; Anagnostou, Valsamo; Pagel, Kymberleigh A; Karchin, Rachel","year":2020,"journal":"Cancer immunology research, 8(3), 396-408","doi":"10.1158/2326-6066.CIR-19-0464","pmid":"31871119","tags":["cancer-research","immune-function","peptide-identification"],"studyType":"computational","evidenceStrength":"moderate","keyFinding":"MHCnuggets deep neural network achieved improved prediction of MHC class I and II neoantigen binding, with better support for rare alleles and scalability to large datasets compared to existing tools.","whyItMatters":"Accurately predicting which neoantigens will be presented to T cells is essential for personalized cancer immunotherapy. Better predictions mean better patient selection and vaccine design.","specificNumbers":"26.3M allele-peptide comparisons; <2.3 hours; 101,326 predicted IMMs; 38 hotspot genes; 24 driver genes; 4x PPV improvement","methodology":"Deep neural network trained on MHC binding data for peptide-MHC affinity prediction. Validated against benchmark datasets. Compared performance with existing predictors for accuracy, allele coverage, and computational scalability.","limitations":"Computational predictions — binding prediction does not guarantee immunogenicity. Model accuracy depends on training data availability per allele. Experimental validation of predictions needed."},{"rthcId":"RPEP-05126","title":"Mass Spectrometry-Based Identification of Urinary Antimicrobial Peptides in Dairy Cows.","authors":"Sharma, Ambika; Nigam, Rajesh; Kumar, Ashish; Singh, Simmi","year":2020,"journal":"Protein and peptide letters, 27(3), 225-235","doi":"10.2174/0929866526666191025105038","pmid":"31654508","tags":["defensins","antimicrobial-peptides"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"MALDI-TOF-MS identified antimicrobial peptides including beta-defensins in dairy cow urine, with confirmed antimicrobial activity. This is the first such characterization using this technique in bovine urine.","whyItMatters":"Understanding where antimicrobial peptides are expressed in cattle could improve veterinary disease management and reduce antibiotic use in dairy farming.","specificNumbers":"4 defensins (DEFB1, DFB4A, DEF1, DEF3); MIC 2.93-29.3 µM/L; active vs gram+ and gram- bacteria","methodology":"Urine from healthy cycling dairy cows processed by diafiltration, ion exchange chromatography, RP-HPLC, and acid extraction. Identified by MALDI-TOF mass spectrometry. Antimicrobial activity confirmed against test organisms.","limitations":"Descriptive study — functional significance of urinary AMPs not established. Limited to healthy cows; disease states may alter profiles. No comparison across breeds or lactation stages."},{"rthcId":"RPEP-05127","title":"What's Love Got to do with it: Role of oxytocin in trauma, attachment and resilience.","authors":"Sharma, Samata R; Gonda, Xenia; Dome, Peter; Tarazi, Frank I","year":2020,"journal":"Pharmacology & therapeutics, 214, 107602","doi":"10.1016/j.pharmthera.2020.107602","pmid":"32512017","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05128","title":"Risuteganib-a novel integrin inhibitor for the treatment of non-exudative (dry) age-related macular degeneration and diabetic macular edema.","authors":"Shaw, Lincoln T; Mackin, Anna; Shah, Reanna; Jain, Siona; Jain, Prisha; Nayak, Ravi; Hariprasad, Seenu M","year":2020,"journal":"Expert opinion on investigational drugs, 29(6), 547-554","doi":"10.1080/13543784.2020.1763953","pmid":"32349559","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05129","title":"The unique antimicrobial peptide repertoire of stick insects.","authors":"Shelomi, Matan; Jacobs, Chris; Vilcinskas, Andreas; Vogel, Heiko","year":2020,"journal":"Developmental and comparative immunology, 103, 103471","doi":"10.1016/j.dci.2019.103471","pmid":"31634521","tags":["antimicrobial-peptides","defensins","immune-function"],"studyType":"basic science","evidenceStrength":"preliminary","keyFinding":"Stick insects possess a unique AMP repertoire including ancestral innate immunity genes lost by later insect clades, revealed by immune challenge and transcriptomic analysis.","whyItMatters":"Understanding the evolutionary history of antimicrobial peptides across insects reveals how immunity diversifies and may uncover novel AMPs with unique antimicrobial properties.","specificNumbers":"5 AMP families; 45 LPS-binding proteins; multiple novel cysteine-rich peptides identified","methodology":"Immune challenge of Peruphasma schultei stick insects with microbial elicitor mixture. Transcriptomic analysis of the immune response to identify and characterize antimicrobial peptide genes.","limitations":"Single species studied. Functional characterization of identified AMPs not complete. Ecological significance of the unique repertoire unclear."},{"rthcId":"RPEP-05130","title":"Physiological and Therapeutic Roles of Neuropeptide Y on Biological Functions.","authors":"Shende, Pravin; Desai, Drashti","year":2020,"journal":"Advances in experimental medicine and biology, 1237, 37-47","doi":"10.1007/5584_2019_427","pmid":"31468359","tags":["neuropeptide-y","neuropeptides","appetite-regulation"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"NPY acts through multiple receptor subtypes (Y1-Y5) to regulate appetite, cardiovascular tone, respiratory function, GI motility, and endocrine systems, with therapeutic implications for multiple disease areas.","whyItMatters":"NPY is one of the most widespread and abundant neuropeptides in the human body. Understanding its diverse roles is essential for developing targeted therapies that modulate specific NPY pathways without disrupting others.","specificNumbers":"6 receptor subtypes (Y1-Y6); roles in 5+ organ systems","methodology":"Comprehensive literature review covering NPY physiology across central nervous, cardiovascular, respiratory, gastrointestinal, and endocrine systems.","limitations":"Broad review — may lack depth in specific areas. Therapeutic applications remain largely at preclinical stages. NPY receptor subtype-specific drugs have been difficult to develop."},{"rthcId":"RPEP-05131","title":"Cathelicidin-DM is an Antimicrobial Peptide from Duttaphrynus melanostictus and Has Wound-Healing Therapeutic Potential.","authors":"Shi, Yaoqiang; Li, Chao; Wang, Mei; Chen, Zijun; Luo, Ying; Xia, Xue-Shan; Song, Yuzhu; Sun, Yi; Zhang, A-Mei","year":2020,"journal":"ACS omega, 5(16), 9301-9310","doi":"10.1021/acsomega.0c00189","pmid":"32363280","tags":["cathelicidins","antimicrobial-peptides","wound-healing"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Cathelicidin-DM from D. melanostictus demonstrated broad-spectrum antimicrobial activity via membrane disruption and wound-healing properties in both in vitro and in vivo models.","whyItMatters":"Amphibians produce some of the most potent antimicrobial peptides in nature. This study provides scientific validation for a traditional medicine while identifying a peptide with dual antimicrobial and wound-healing properties.","specificNumbers":"37 amino acids; kills bacteria in 15 min; comparable to melittin; enriched at infection site","methodology":"Identified cathelicidin-DM gene from D. melanostictus. Tested antimicrobial activity in vitro against multiple pathogens. Assessed wound-healing efficacy in animal models. Investigated mechanism of action.","limitations":"Small animal study. Stability and bioavailability of cathelicidin-DM not characterized. Toxicity profile incomplete. Manufacturing scalability not addressed."},{"rthcId":"RPEP-05132","title":"Paneth cell α-defensin misfolding correlates with dysbiosis and ileitis in Crohn's disease model mice.","authors":"Shimizu, Yu; Nakamura, Kiminori; Yoshii, Aki; Yokoi, Yuki; Kikuchi, Mani; Shinozaki, Ryuga; Nakamura, Shunta; Ohira, Shuya; Sugimoto, Rina; Ayabe, Tokiyoshi","year":2020,"journal":"Life science alliance, 3(6)","doi":"10.26508/lsa.201900592","pmid":"32345659","tags":["defensins","gut-health","antimicrobial-peptides"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"ER stress-induced α-defensin misfolding in Paneth cells correlated with intestinal dysbiosis and ileitis in a Crohn's disease mouse model, supporting a causal link between defensin dysfunction and IBD pathophysiology.","whyItMatters":"If defensin misfolding drives the microbiome disruption underlying Crohn's disease, restoring proper defensin function could be a novel therapeutic approach rather than just suppressing inflammation.","specificNumbers":"Misfolded defensins lacked disulfide bonds; correlated with disease progression; directly caused dysbiosis in WT mice","methodology":"Crohn's disease mouse model with assessment of Paneth cell ER stress, α-defensin folding status, intestinal microbiota composition (dysbiosis), and ileitis severity.","limitations":"Small mouse study — human Crohn's is more complex. Correlation shown but strict causation requires further experiments. Single model system. ER stress has multiple downstream effects beyond defensin misfolding."},{"rthcId":"RPEP-05133","title":"Neuropeptide Y deficiency induces anxiety-like behaviours in zebrafish (Danio rerio).","authors":"Shiozaki, Kazuhiro; Kawabe, Momoko; Karasuyama, Kiwako; Kurachi, Takayoshi; Hayashi, Akito; Ataka, Koji; Iwai, Haruki; Takeno, Hinako; Hayasaka, Oki; Kotani, Tomonari; Komatsu, Masaharu; Inui, Akio","year":2020,"journal":"Scientific reports, 10(1), 5913","doi":"10.1038/s41598-020-62699-0","pmid":"32246073","tags":["neuropeptide-y","neuropeptides","mental-health"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"NPY-knockout zebrafish exhibited anxiety-like behaviors with increased brain pomc and avp mRNA levels, demonstrating NPY's anxiolytic role is evolutionarily conserved across vertebrates.","whyItMatters":"Confirming NPY's anti-anxiety role across species strengthens the case for NPY-based therapies for anxiety disorders and validates zebrafish as a model for studying neuropeptide-mood interactions.","specificNumbers":"Elevated pomc, avp, orx, cck, gr, mr, th1, th2 mRNA; decreased social interaction; decreased locomotion; stress vulnerability","methodology":"Generated NPY gene-knockout zebrafish. Assessed growth, anxiety-like behaviors using standard zebrafish behavioral assays, brain neuropeptide gene expression (pomc, avp), and catecholamine levels.","limitations":"Zebrafish model — behavioral assays are simpler than mammalian anxiety tests. Complete NPY absence is more extreme than natural variation. Small sample typical for zebrafish genetics."},{"rthcId":"RPEP-05134","title":"Anti-Hypertensive Effects of Peptides Derived from Rice Bran Protein.","authors":"Shobako, Naohisa; Ohinata, Kousaku","year":2020,"journal":"Nutrients, 12(10)","doi":"10.3390/nu12103060","pmid":"33036355","tags":["bioactive-peptides","food-derived-peptides","cardiovascular-health"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Rice bran-derived peptides demonstrate anti-hypertensive activity primarily through ACE inhibition, with evidence from both in vitro and animal studies.","whyItMatters":"Hypertension affects over 1 billion people. Food-derived ACE-inhibitory peptides could provide a natural, side-effect-free approach to blood pressure management, especially using an abundant waste product like rice bran.","specificNumbers":"Multiple ACE-inhibitory peptides identified from rice bran protein hydrolysates","methodology":"Literature review of rice bran protein hydrolysis, identification of ACE-inhibitory peptides, and their anti-hypertensive effects in preclinical models.","limitations":"Review format. Most evidence from in vitro and animal studies. Human clinical trials with rice bran peptides for blood pressure are limited. Bioavailability after oral ingestion needs characterization."},{"rthcId":"RPEP-05135","title":"A new insight into thymosin β4, a promising therapeutic approach for neurodegenerative disorders.","authors":"Shomali, Navid; Baradaran, Behzad; Deljavanghodrati, Mina; Akbari, Morteza; Hemmatzadeh, Maryam; Mohammadi, Hamed; Jang, Yue; Xu, Huaxi; Sandoghchian Shotorbani, Siamak","year":2020,"journal":"Journal of cellular physiology, 235(4), 3270-3279","doi":"10.1002/jcp.29293","pmid":"31612500","tags":["thymosin-beta-4","neuroprotection","neurological-conditions"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Tβ4 promotes neurological recovery through neurovascular remodeling, CNS plasticity enhancement, and modulation of Toll-like receptor/NF-κB inflammatory signaling pathways, with microRNA-mediated regulation.","whyItMatters":"Neurodegenerative diseases like Alzheimer's and Parkinson's lack effective treatments. Tβ4's dual ability to reduce neuroinflammation and promote brain repair makes it a compelling therapeutic candidate.","specificNumbers":"Proposed pathway: TB4 → miR-146a ↑ → IRAK1 ↓ → NF-kB ↓; acts on oligodendrocytes, neurons, microglia","methodology":"Literature review covering Tβ4 mechanisms in neurological recovery, focusing on anti-inflammatory pathways, neurovascular remodeling, and CNS plasticity in neurodegenerative disease models.","limitations":"Review of preclinical evidence — no human clinical trial data for neurodegenerative indications. Blood-brain barrier penetration and optimal dosing not established. Multiple mechanisms make it difficult to predict clinical outcomes."},{"rthcId":"RPEP-05136","title":"Cell-Penetrating Peptide Modified PEG-PLA Micelles for Efficient PTX Delivery.","authors":"Shuai, Qi; Cai, Yue; Zhao, Guangkuo; Sun, Xuanrong","year":2020,"journal":"International journal of molecular sciences, 21(5)","doi":"10.3390/ijms21051856","pmid":"32182734","tags":["cell-penetrating-peptides","cancer-research","drug-delivery-systems"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"CPP-functionalized PEG-PLA micelles improved paclitaxel bioavailability, cellular uptake, and anti-tumor efficacy while reducing side effects in animal cancer models.","whyItMatters":"Paclitaxel is a widely used chemotherapy drug limited by poor solubility and side effects. CPP-modified micelles could deliver it more effectively to tumors while sparing healthy tissue.","specificNumbers":"~20 nm particles; enhanced in vitro cytotoxicity; faster plasma clearance in vivo; reduced antitumor effect vs unmodified NPs","methodology":"Synthesized CPP-modified PEG-PLA block copolymer micelles loaded with paclitaxel. Tested cellular uptake, anti-tumor efficacy, and toxicity in animal cancer models compared to unmodified micelles and free drug.","limitations":"Animal study — human pharmacokinetics may differ. Manufacturing scalability and regulatory pathway for CPP-modified micelles not addressed. Long-term toxicity unknown."},{"rthcId":"RPEP-05137","title":"Fistulas Healing. Stable Gastric Pentadecapeptide BPC 157 Therapy.","authors":"Sikiric, Predrag; Drmic, Domagoj; Sever, Marko; Klicek, Robert; Blagaic, Alenka B; Tvrdeic, Ante; Kralj, Tamara; Kovac, Katarina K; Vukojevic, Jaksa; Siroglavic, Marko; Gojkovic, Slaven; Krezic, Ivan; Pavlov, Katarina H; Rasic, Domagoj; Mirkovic, Ivan; Kokot, Antonio; Skrtic, Anita; Seiwerth, Sven","year":2020,"journal":"Current pharmaceutical design, 26(25), 2991-3000","doi":"10.2174/1381612826666200424180139","pmid":"32329684","tags":["bpc-157","wound-healing","gut-health"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"BPC-157 consistently promoted fistula healing in rat models across multiple organ systems, with effects linked to its anti-ulcer, cytoprotective, and wound-healing properties as a native gastric peptide.","whyItMatters":"Fistulas are serious surgical complications often resistant to treatment. If BPC-157's consistent rat results translate to humans, it could offer a non-surgical fistula healing approach.","specificNumbers":"6+ external fistula types; internal fistulas (colovesical, rectovaginal); 7 anastomosis types; no LD1 found; stable in gastric juice >24h","methodology":"Literature review of BPC-157 studies in rat fistula models, covering gastrointestinal and other organ system fistulas, mechanism of action, and connection to cytoprotection.","limitations":"All data from rat models — no human fistula healing trials. BPC-157 is not FDA-approved. Mechanisms remain partially understood. Review from researchers heavily involved in BPC-157 research."},{"rthcId":"RPEP-05138","title":"Stable Gastric Pentadecapeptide BPC 157, Robert's Stomach Cytoprotection/Adaptive Cytoprotection/Organoprotection, and Selye's Stress Coping Response: Progress, Achievements, and the Future.","authors":"Sikiric, Predrag; Hahm, Ki-Baik; Blagaic, Alenka Boban; Tvrdeic, Ante; Pavlov, Katarina Horvat; Petrovic, Andrea; Kokot, Antonio; Gojkovic, Slaven; Krezic, Ivan; Drmic, Domagoj; Rucman, Rudolf; Seiwerth, Sven","year":2020,"journal":"Gut and liver, 14(2), 153-167","doi":"10.5009/gnl18490","pmid":"31158953","tags":["bpc-157","wound-healing","gut-health"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"BPC-157 demonstrates protective effects across multiple organ systems beyond the stomach, including endothelial protection, vessel recruitment around occlusions, and counteraction of cancer cachexia through modulation of FoxO3a, p-AKT, p-mTOR, and p-GSK-3β pathways.","whyItMatters":"By connecting BPC-157 to established physiological concepts like Robert's cytoprotection and Selye's stress response, this review provides a theoretical framework for understanding how a single gastric peptide might exert such wide-ranging protective effects.","specificNumbers":"Multiple organ systems protected; modulates FoxO3a, p-AKT, p-mTOR, p-GSK-3β in muscle; counters IL-6 and TNF-α","methodology":"Narrative review synthesizing published preclinical evidence on BPC-157 across cytoprotection, organoprotection, vascular effects, and anti-cachexia mechanisms.","limitations":"As a narrative review, the paper primarily synthesizes preclinical animal data. Most of the cited evidence comes from a single research group. Human clinical trials are largely absent, and the breadth of claimed effects warrants cautious interpretation."},{"rthcId":"RPEP-05139","title":"Repurposing a peptide toxin from wasp venom into antiinfectives with dual antimicrobial and immunomodulatory properties.","authors":"Silva, Osmar N; Torres, Marcelo D T; Cao, Jicong; Alves, Elaine S F; Rodrigues, Leticia V; Resende, Jarbas M; Lião, Luciano M; Porto, William F; Fensterseifer, Isabel C M; Lu, Timothy K; Franco, Octavio L; de la Fuente-Nunez, Cesar","year":2020,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 117(43), 26936-26945","doi":"10.1073/pnas.2012379117","pmid":"33046640","tags":["antimicrobial-peptides","venom-derived-peptides","immune-function"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"The engineered peptide mast-MO showed dual antimicrobial and immunomodulatory activity — directly killing bacteria through membrane permeabilization while recruiting leukocytes and controlling inflammation in animal infection models.","whyItMatters":"With antibiotic resistance rising globally, this study demonstrates a viable strategy for turning natural venom toxins into safe, effective antimicrobials that fight bacteria through mechanisms resistant pathogens haven't evolved defenses against.","specificNumbers":"Comparable to standard antibiotics; potentiated multiple drug classes; toxicity removed by permutation; α-helical by NMR","methodology":"Rational peptide engineering with NMR structural analysis, in vitro antibacterial assays, antibiotic synergy testing, mechanism-of-action studies, and in vivo animal infection models with toxicity optimization through permutation studies.","limitations":"Results are from animal models and have not been tested in human clinical trials. Peptide stability, bioavailability, and manufacturing scalability for clinical use remain unaddressed. Long-term toxicity profiles need further evaluation."},{"rthcId":"RPEP-05140","title":"Automated Design of Macrocycles for Therapeutic Applications: From Small Molecules to Peptides and Proteins.","authors":"Sindhikara, Dan; Wagner, Michael; Gkeka, Paraskevi; Güssregen, Stefan; Tiwari, Garima; Hessler, Gerhard; Yapici, Engin; Li, Ziyu; Evers, Andreas","year":2020,"journal":"Journal of medicinal chemistry, 63(20), 12100-12115","doi":"10.1021/acs.jmedchem.0c01500","pmid":"33017535","tags":["peptide-synthesis","drug-delivery-systems","peptide-modifications"],"studyType":"computational","evidenceStrength":"moderate","keyFinding":"The automated platform successfully generates and ranks macrocyclic designs across molecular scales, from small molecules through peptides to PROTACs and proteins, using established chemical reactions and reagents.","whyItMatters":"Ring-shaped molecules often make better drugs than their linear counterparts — they bind more tightly, resist enzymatic breakdown, and can penetrate cells more easily. Automating their design could dramatically accelerate drug development timelines.","specificNumbers":"Applicable to small molecules, peptides, PROTACs; validated prospectively and retrospectively","methodology":"Computational approach using 3D protein-ligand structures as input, automated linker generation from a reaction library, geometric compatibility evaluation, and ranking by conformational stability. Validated with prospective and retrospective case studies.","limitations":"Computational predictions of binding and stability require experimental validation. The tool relies on known chemical reactions, potentially missing novel cyclization strategies. Manufacturing feasibility of proposed designs is not assessed."},{"rthcId":"RPEP-05141","title":"Quantitative Profiling of Synuclein Species: Application to Transgenic Mouse Models of Parkinson's Disease.","authors":"Singh, Serena; Khayachi, Anouar; Milnerwood, Austen J; DeMarco, Mari L","year":2020,"journal":"Journal of Parkinson's disease, 10(2), 613-621","doi":"10.3233/JPD-191835","pmid":"32083592","tags":["biomarkers","peptide-identification","neurological-conditions"],"studyType":"methods paper","evidenceStrength":"preliminary","keyFinding":"The MRM LC-MS/MS assay quantifies total alpha-synuclein, species-specific contributions, combined alpha/beta-synuclein, and post-translational modification signatures in a single streamlined analysis with wide linear range.","whyItMatters":"Better tools to measure synuclein proteins are essential for Parkinson's disease research. This method provides more detailed and reliable measurements than existing techniques, potentially accelerating preclinical drug development.","specificNumbers":"6 proteotypic peptides; 3 species-specific; 3 conserved; linear over ≥1 order of magnitude","methodology":"Development and validation of a multiple reaction monitoring LC-MS/MS assay using proteolytic digestion of six proteotypic peptides, labeled internal standards, and external calibration curves. Validated in M83 transgenic PD mouse brain tissue versus wild-type controls.","limitations":"Validated only in transgenic mouse brain tissue with a small sample size. Application to human tissues and biofluids like cerebrospinal fluid remains to be demonstrated. The method measures soluble synucleins but may not capture aggregated forms."},{"rthcId":"RPEP-05142","title":"Theta-Defensins Inhibit High-Risk Human Papillomavirus Infection Through Charge-Driven Capsid Clustering.","authors":"Skeate, Joseph G; Segerink, Wouter H; Garcia, Mauricio D; Fernandez, Daniel J; Prins, Ruben; Lühen, Kim P; Voss, Féline O; Da Silva, Diane M; Kast, W Martin","year":2020,"journal":"Frontiers in immunology, 11, 561843","doi":"10.3389/fimmu.2020.561843","pmid":"33154746","tags":["defensins","antimicrobial-peptides","immune-function"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Rhesus theta defensin 1 (RTD-1) inhibits high-risk HPV infection through charge-driven capsid clustering that prevents virions from binding to cell surface receptor complexes.","whyItMatters":"Despite HPV vaccines, transmission continues and not everyone is vaccinated. A topical antiviral peptide that physically blocks HPV from infecting cells could provide an additional prevention strategy, especially for genotypes not covered by current vaccines.","specificNumbers":"18-amino-acid cyclic peptide; blocked hrHPV; mechanism: capsid clustering","methodology":"In vitro infection assays testing theta-defensin RTD-1 against high-risk HPV genotypes, with mechanistic studies examining capsid clustering and receptor binding inhibition.","limitations":"Results are from cell culture experiments only — no animal or human testing has been performed. The peptides are derived from monkeys and would need modification for human therapeutic use. Effectiveness against all HPV genotypes was not fully tested."},{"rthcId":"RPEP-05143","title":"Cholecystokinin in the central nervous system of the sea lamprey Petromyzon marinus: precursor identification and neuroanatomical relationships with other neuronal signalling systems.","authors":"Sobrido-Cameán, D; Yáñez-Guerra, L A; Robledo, D; López-Varela, E; Rodicio, M C; Elphick, M R; Anadón, R; Barreiro-Iglesias, Antón","year":2020,"journal":"Brain structure & function, 225(1), 249-284","doi":"10.1007/s00429-019-01999-2","pmid":"31807925","tags":["cholecystokinin","neuropeptides","gut-peptides"],"studyType":"basic science","evidenceStrength":"moderate","keyFinding":"The sea lamprey CCK-8 peptide is highly similar to mammalian CCK, with CCK neurons distributed across hypothalamus, midbrain, and brainstem regions, and showing the first documented GABA-CCK co-localization in a non-mammalian vertebrate.","whyItMatters":"Understanding CCK in the most ancient vertebrates reveals which aspects of this gut-brain signaling system are fundamental to all vertebrates, providing evolutionary context for how CCK regulates appetite, digestion, and mood in humans.","specificNumbers":"8+ brain regions with CCK neurons; first GABA/CCK co-localization in non-mammal; adult-specific populations","methodology":"cDNA cloning and sequencing, mRNA in situ hybridization for neuron mapping, custom antiserum generation for immunohistochemistry, and co-localization studies with GABA, glutamate, serotonin, tyrosine hydroxylase, and neuropeptide Y.","limitations":"Study is limited to neuroanatomical mapping in one species and does not test CCK function in the lamprey. Differences between larval and adult expression patterns complicate interpretation. Findings may not directly translate to understanding CCK function in mammals."},{"rthcId":"RPEP-05144","title":"Improving NK1R-targeted gene delivery of stearyl-antimicrobial peptide CAMEL by conjugating it with substance P.","authors":"Song, Jingjing; Huang, Sujie; Ma, Panpan; Zhang, Bao; Jia, Bo; Zhang, Wei","year":2020,"journal":"Bioorganic & medicinal chemistry letters, 30(16), 127353","doi":"10.1016/j.bmcl.2020.127353","pmid":"32631551","tags":["substance-p","cell-penetrating-peptides","cancer-research"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"The substance P-conjugated vector stearyl-CMSP showed significant transfection specificity for NK1R-expressing cells, with stearyl-CMSP/p53 complexes displaying higher antiproliferative activity against NK1R-positive cells versus NK1R-negative cells.","whyItMatters":"Non-viral gene therapy for cancer is limited by lack of specificity — treatments that affect all cells cause toxic side effects. This simple conjugation strategy could make peptide-based gene delivery precise enough for clinical cancer applications.","specificNumbers":"11-amino-acid SP targeting; NK1R-specific transfection; selective antiproliferative activity with p53 delivery","methodology":"In vitro gene delivery study comparing stearyl-CAMEL and stearyl-CMSP vectors in NK1R-expressing (HEK293-NK1R) versus control (HEK293) cells, measuring transfection efficiency and antiproliferative activity with p53 plasmid delivery.","limitations":"Results are from cell culture only using engineered cell lines that overexpress NK1R. In vivo biodistribution, toxicity, and tumor targeting have not been tested. The p53 gene therapy payload may not be optimal for all cancer types."},{"rthcId":"RPEP-05145","title":"Thymosin beta 4 attenuates PrP(106-126)-induced human brain endothelial cells dysfunction.","authors":"Song, Kibbeum; Han, Hye-Ju; Kim, Sokho; Kwon, Jungkee","year":2020,"journal":"European journal of pharmacology, 869, 172891","doi":"10.1016/j.ejphar.2019.172891","pmid":"31877278","tags":["thymosin-beta-4","neuroprotection","neurological-conditions"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Thymosin beta-4 increased tight junction protein expression, reduced the F-actin to G-actin ratio, and significantly improved vascular permeability dysfunction caused by PrP(106-126) in human brain endothelial cells.","whyItMatters":"Blood-brain barrier breakdown is a key feature of prion diseases and other neurodegenerative conditions. Finding that a naturally occurring peptide can stabilize this barrier suggests a potential protective strategy against prion-induced brain damage.","specificNumbers":"Increased tight junction proteins; reduced F-actin/G-actin ratio; improved barrier permeability","methodology":"In vitro study using hCMEC/D3 human cerebral endothelial cells and a BBB model, measuring tight junction protein expression, actin dynamics (F-actin/G-actin ratio), and vascular permeability after PrP(106-126) exposure with and without Tβ4 treatment.","limitations":"Study uses a single cell line in culture, which cannot fully replicate the complexity of the BBB in a living brain. No animal or human testing was performed. The PrP(106-126) fragment may not perfectly represent full-length prion protein effects."},{"rthcId":"RPEP-05146","title":"Enzymatic hydrolysis of insect Alphitobius diaperinus towards the development of bioactive peptide hydrolysates.","authors":"Sousa, Pedro; Borges, Sandra; Pintado, Manuela","year":2020,"journal":"Food & function, 11(4), 3539-3548","doi":"10.1039/d0fo00188k","pmid":"32255460","tags":["bioactive-peptides","food-derived-peptides","cardiovascular-health"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Insect protein hydrolysates showed strong antioxidant activity (up to 944.8 μmol Trolox equivalent/g by ORAC) and ACE inhibition (IC50 as low as 55.5 μg protein/mL), but no antimicrobial or antidiabetic activity.","whyItMatters":"As the world searches for sustainable protein sources, demonstrating that insect proteins can yield health-promoting bioactive peptides adds nutritional value beyond basic protein content, making insect-based foods more attractive to consumers and the food industry.","specificNumbers":"ABTS: ~95 µmol TE/g; ORAC: 826-945 µmol TE/g; ACE IC50: 55.5 µg/mL (Alcalase), 107.4 µg/mL (Corolase); no antimicrobial/antidiabetic activity","methodology":"Enzymatic hydrolysis of Alphitobius diaperinus protein using Alcalase 2.5L and Corolase PP at optimized conditions, followed by ABTS and ORAC antioxidant assays, ACE inhibition testing, and antimicrobial and antidiabetic screening.","limitations":"All bioactivity was measured in test tubes, not in animals or humans. ACE inhibition in vitro does not guarantee blood pressure reduction in vivo. Individual bioactive peptide sequences were not identified. Consumer acceptance of insect-derived ingredients remains a barrier."},{"rthcId":"RPEP-05147","title":"Rationale, design, and methods of the Autism Centers of Excellence (ACE) network Study of Oxytocin in Autism to improve Reciprocal Social Behaviors (SOARS-B).","authors":"Spanos, Marina; Chandrasekhar, Tara; Kim, Soo-Jeong; Hamer, Robert M; King, Bryan H; McDougle, Christopher J; Sanders, Kevin B; Gregory, Simon G; Kolevzon, Alexander; Veenstra-VanderWeele, Jeremy; Sikich, Linmarie","year":2020,"journal":"Contemporary clinical trials, 98, 106103","doi":"10.1016/j.cct.2020.106103","pmid":"32777383","tags":["oxytocin","neurological-conditions","clinical-applications"],"studyType":"clinical trial design","evidenceStrength":"not yet reported","keyFinding":"SOARS-B enrolled 290 participants across seven sites for a 24-week randomized trial of intranasal oxytocin in ASD, making it the best-powered study to date.","whyItMatters":"Previous small oxytocin-autism studies produced conflicting results. This large trial aims to definitively determine whether intranasal oxytocin improves social behaviors in children with ASD.","specificNumbers":"n=290; ages 3-17; 7 sites; 24 weeks double-blind + 24 weeks open-label; plasma oxytocin and OXTR methylation measured","methodology":"Phase 2 randomized, placebo-controlled, multi-site clinical trial with 24 weeks blinded treatment, 24 weeks open-label extension, and biomarker measurements.","limitations":"Design paper only — no results reported. Trial outcomes are not yet available in this publication."},{"rthcId":"RPEP-05148","title":"Medications Approved for Preventing Migraine Headaches.","authors":"Spindler, Brittany L; Ryan, Melody","year":2020,"journal":"The American journal of medicine, 133(6), 664-667","doi":"10.1016/j.amjmed.2020.01.031","pmid":"32145209","tags":["cgrp","neuropeptides","migraine"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Three CGRP-targeting monoclonal antibodies are FDA-approved for migraine prevention, reducing attack frequency through a targeted mechanism not available with older drugs.","whyItMatters":"Migraine affects 1 in 7 people ages 15-49 and is 3 times more common in women. These first-in-class targeted preventive medications fill a critical gap for patients who couldn't tolerate existing treatments.","specificNumbers":"39M Americans; 1 in 7 ages 15-49; 3x more in women; 3 FDA-approved mAbs","methodology":"Review of clinical trial data and FDA-approved indications for erenumab, fremanezumab, and galcanezumab.","limitations":"Brief review without detailed comparative efficacy data. Long-term safety beyond trial durations is still being monitored."},{"rthcId":"RPEP-05149","title":"Influence of Production Process and Scale on Quality of Polypeptide Drugs: a Case Study on GLP-1 Analogs.","authors":"Staby, Arne; Steensgaard, Dorte Bjerre; Haselmann, Kim F; Marino, Jesper Søndergaard; Bartholdy, Christina; Videbæk, Nicoline; Schelde, Ole; Bosch-Traberg, Heidrun; Spang, Lotte Touborg; Asgreen, Désirée J","year":2020,"journal":"Pharmaceutical research, 37(7), 120","doi":"10.1007/s11095-020-02817-9","pmid":"32514880","tags":["glp-1-receptor-agonists","peptide-synthesis","clinical-applications"],"studyType":"analytical","evidenceStrength":"moderate","keyFinding":"Manufacturing differences between originator and follow-on GLP-1 analogs produce distinct impurity profiles with potential immunogenicity implications, requiring clinical evaluation.","whyItMatters":"As GLP-1 agonists become blockbuster drugs, follow-on versions are entering the market. Manufacturing differences can meaningfully affect quality in ways requiring safety evaluation.","specificNumbers":"5 alternative suppliers vs originator; distinct impurity profiles; trace metals ↑ HMW formation; semaglutide immunogenicity < liraglutide in SUSTAIN","methodology":"Analytical comparison of drug substances from multiple suppliers, in silico T cell epitope prediction, and clinical immunogenicity data from SUSTAIN trials.","limitations":"In silico immunogenicity predictions require clinical confirmation. Not all suppliers may represent actual marketed products."},{"rthcId":"RPEP-05150","title":"Cervical Gene Delivery of the Antimicrobial Peptide, Human β-Defensin (HBD)-3, in a Mouse Model of Ascending Infection-Related Preterm Birth.","authors":"Suff, Natalie; Karda, Rajvinder; Diaz, Juan Antinao; Ng, Joanne; Baruteau, Julien; Perocheau, Dany; Taylor, Peter W; Alber, Dagmar; Buckley, Suzanne M K; Bajaj-Elliott, Mona; Waddington, Simon N; Peebles, Donald","year":2020,"journal":"Frontiers in immunology, 11, 106","doi":"10.3389/fimmu.2020.00106","pmid":"32117260","tags":["defensins","antimicrobial-peptides","gene-therapy"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Cervical gene delivery of HBD3 significantly reduced uterine bacterial bioluminescence and increased the number of live-born pups compared to controls in an ascending infection model.","whyItMatters":"Preterm birth from ascending infection is a major cause of neonatal mortality. Augmenting the cervix's natural antimicrobial peptide defenses could prevent infections without antibiotics.","specificNumbers":"40% of preterm births infection-related; significant reduction in uterine bacteria at 24h; significant increase in live pups","methodology":"AAV8 vector with HBD3 gene administered intravaginally to pregnant mice at E13.5, E. coli K1 infection induced at E16.5, bioluminescence imaging for bacterial tracking.","limitations":"Mouse model may not translate to human pregnancy. Single bacterial species tested. Long-term safety of viral vector delivery during pregnancy unknown."},{"rthcId":"RPEP-05151","title":"Development of Cell-Penetration PG-Surfactants and Its Application in External Peptide Delivery to Cytosol.","authors":"Sumito, Natsumi; Koeda, Shuhei; Umezawa, Naoki; Inoue, Yasumichi; Tsukiji, Shinya; Higuchi, Tsunehiko; Mizuno, Toshihisa","year":2020,"journal":"Bioconjugate chemistry, 31(3), 821-833","doi":"10.1021/acs.bioconjchem.9b00877","pmid":"31940181","tags":["cell-penetrating-peptides","drug-delivery-systems","peptide-modifications"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"CP-PGs with tri-lysine sequences (DKCK12-K3 and DKCK12-K5) showed lower cytotoxicity and superior peptide delivery compared to the well-established R8 cell-penetrating peptide.","whyItMatters":"Getting therapeutic peptides inside cells remains a major drug delivery challenge. These new carriers achieve better delivery than established CPPs while maintaining low toxicity.","specificNumbers":"EC50: 5.8-6.2 µM (best) vs 6.8 µM (R8); IC50: 198-241 µM (K3) vs 88 µM (R3); two C12 chains","methodology":"Peptide synthesis, cytotoxicity assays on NIH3T3 cells, proapoptotic peptide (PAD) delivery assays measuring cell death as a functional readout of cytosolic delivery.","limitations":"In vitro only using a single cell line. Functional readout based on apoptotic activity rather than direct delivery measurement. No in vivo data."},{"rthcId":"RPEP-05152","title":"Research advances of vasoactive intestinal peptide in the pathogenesis of ulcerative colitis by regulating interleukin-10 expression in regulatory B cells.","authors":"Sun, Xiong; Huang, Yao; Zhang, Ya-Li; Qiao, Dan; Dai, Yan-Cheng","year":2020,"journal":"World journal of gastroenterology, 26(48), 7593-7602","doi":"10.3748/wjg.v26.i48.7593","pmid":"33505138","tags":["vip","gut-health","immune-function"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"VIP regulates IL-10 expression in regulatory B cells, influencing the Th1/Th2 balance and potentially providing a new mechanism for treating ulcerative colitis.","whyItMatters":"Ulcerative colitis has increasing global incidence with limited treatment options. VIP's ability to modulate gut immunity through regulatory B cells could lead to novel, targeted therapies.","specificNumbers":"Proposed pathway: VIP → Bregs → IL-10 → Th2 shift; Bregs produce IL-10, IL-35, TGF-β","methodology":"Narrative review of published literature on VIP immunomodulation and regulatory B cell biology in colitis.","limitations":"Review of an evolving field. The exact mechanisms of VIP-Breg-IL-10 interaction are still being clarified."},{"rthcId":"RPEP-05153","title":"Pharmacokinetics, Pharmacodynamics and Drug-Drug Interactions of New Anti-Migraine Drugs-Lasmiditan, Gepants, and Calcitonin-Gene-Related Peptide (CGRP) Receptor Monoclonal Antibodies.","authors":"Szkutnik-Fiedler, Danuta","year":2020,"journal":"Pharmaceutics, 12(12)","doi":"10.3390/pharmaceutics12121180","pmid":"33287305","tags":["cgrp","neuropeptides","migraine","clinical-applications"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Gepants and lasmiditan have significant drug interaction potential with CYP3A4 inhibitors, serotonergic drugs, and transporter inhibitors, while CGRP monoclonal antibodies have pharmacodynamic interactions related to immune modulation.","whyItMatters":"Migraine patients often take multiple medications. Understanding drug interactions prevents adverse effects and ensures these new treatments are used safely.","specificNumbers":"7 drugs reviewed; gepants: CYP3A4/P-gp/BCRP; lasmiditan: serotonergic; mAbs: FcγR interactions","methodology":"Review of published pharmacokinetic, pharmacodynamic, and drug interaction data for lasmiditan, gepants, and CGRP monoclonal antibodies.","limitations":"Review based on available data at time of publication. Long-term interaction data and real-world evidence still accumulating."},{"rthcId":"RPEP-05154","title":"Milk whey from different animal species stimulates the in vitro release of CCK and GLP-1 through a whole simulated intestinal digestion.","authors":"Sánchez-Moya, T; Planes-Muñoz, D; Frontela-Saseta, C; Ros-Berruezo, G; López-Nicolás, R","year":2020,"journal":"Food & function, 11(8), 7208-7216","doi":"10.1039/d0fo00767f","pmid":"32756716","tags":["glp-1","bioactive-food-peptides","weight-loss"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Digested whey samples were the most potent CCK and GLP-1 stimulators. Digested goat whey produced the highest GLP-1 release (86.33 pg/mL). Fermented mixture whey produced the highest CCK release (80.78 pg/mL). Undigested whey showed weak hormone stimulation.","whyItMatters":"Understanding which whey proteins produce the most satiety hormones could optimize dairy-based supplements for appetite control and weight management.","specificNumbers":"Goat whey digested: GLP-1 86.33 pg/mL; mixed whey fermented: CCK 80.78 pg/mL; digested > fermented > non-digested","methodology":"In vitro simulated gastrointestinal digestion (oral through colonic fermentation) of whey from cow, sheep, goat, and mixed milks. STC-1 enteroendocrine cell line incubated for 2 hours with non-digested, digested, and fermented samples. Measured CCK and GLP-1 secretion.","limitations":"In vitro cell line study — STC-1 cells may not perfectly replicate human gut hormone responses. Simulated digestion may differ from in vivo digestion. No human satiety or weight loss outcomes measured."},{"rthcId":"RPEP-05155","title":"Biocompatible Ionic Liquid Enhances Transdermal Antigen Peptide Delivery and Preventive Vaccination Effect.","authors":"Tahara, Yoshiro; Morita, Kaho; Wakabayashi, Rie; Kamiya, Noriho; Goto, Masahiro","year":2020,"journal":"Molecular pharmaceutics, 17(10), 3845-3856","doi":"10.1021/acs.molpharmaceut.0c00598","pmid":"32902989","tags":["drug-delivery-systems","cancer-research","peptide-modifications"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Choline-oleate ionic liquid increased transdermal antigen peptide delivery 28-fold and produced superior anti-tumor vaccination effects compared to traditional injection.","whyItMatters":"Needle-free vaccination through the skin could improve compliance and cold chain logistics. This biocompatible formulation achieves better immune responses than injection.","specificNumbers":"28-fold ↑ transdermal flux; 7 fatty acids screened; C18:1 selected; tumor suppression > injection; no skin irritation","methodology":"In vitro skin permeation studies, in vivo tumor growth suppression in vaccinated mice, 3D skin irritation model, and histological assessment.","limitations":"Mouse study with a single antigen peptide. Human skin permeation may differ. Long-term stability of the formulation not assessed."},{"rthcId":"RPEP-05156","title":"The voltage-gated potassium channel KV1.3 as a therapeutic target for venom-derived peptides.","authors":"Tajti, Gabor; Wai, Dorothy C C; Panyi, Gyorgy; Norton, Raymond S","year":2020,"journal":"Biochemical pharmacology, 181, 114146","doi":"10.1016/j.bcp.2020.114146","pmid":"32653588","tags":["venom-derived-peptides","immune-function","ion-channels"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Venom-derived KV1.3 inhibitors show efficacy in animal models of multiple autoimmune diseases, and the ShK analog dalazatide has completed Phase 1 trials for psoriasis.","whyItMatters":"KV1.3 is upregulated in the specific immune cells driving autoimmune diseases, making targeted peptide inhibitors a precision medicine approach with potentially fewer side effects than broad immunosuppression.","specificNumbers":"Dalazatide Phase 1 complete; efficacy in RA, psoriasis, MS models; KV1.3 target for IBD, AD, PD, fibrosis","methodology":"Narrative review of venom peptide pharmacology, KV1.3 biology in autoimmune disease, and clinical development progress.","limitations":"Most efficacy data from animal models. Only dalazatide has reached clinical trials. Brain penetration remains a challenge for neuroinflammatory applications."},{"rthcId":"RPEP-05157","title":"Psoriasis and Antimicrobial Peptides.","authors":"Takahashi, Toshiya; Yamasaki, Kenshi","year":2020,"journal":"International journal of molecular sciences, 21(18)","doi":"10.3390/ijms21186791","pmid":"32947991","tags":["cathelicidins","defensins","antimicrobial-peptides","immune-function"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"AMPs amplify psoriatic inflammation by enhancing recognition of self-DNA/RNA as damage-associated molecular patterns, triggering interferon production from dendritic cells and keratinocytes.","whyItMatters":"Understanding how normally protective antimicrobial peptides paradoxically drive autoimmune skin inflammation could lead to targeted psoriasis therapies.","specificNumbers":"3 AMP families (LL-37, β-defensin, S100); enhance DAMP recognition; drive Th17/Th1; NETs contain LL-37","methodology":"Narrative review of published literature on AMP roles in psoriasis pathogenesis, including LL-37, defensins, S100, and their interactions with immune cells.","limitations":"Review article without new experimental data. Exact therapeutic targeting of AMP-mediated pathways in psoriasis remains to be developed."},{"rthcId":"RPEP-05158","title":"Restoration of Regulatory T-Cell Function in Dry Eye Disease by Antagonizing Substance P/Neurokinin-1 Receptor.","authors":"Taketani, Yukako; Marmalidou, Anna; Dohlman, Thomas H; Singh, Rohan Bir; Amouzegar, Afsaneh; Chauhan, Sunil K; Chen, Yihe; Dana, Reza","year":2020,"journal":"The American journal of pathology, 190(9), 1859-1866","doi":"10.1016/j.ajpath.2020.05.011","pmid":"32473919","tags":["substance-p","immune-function","clinical-applications"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"Substance P promotes Treg dysfunction in DED, and NK1R antagonist treatment restores Treg function, suppresses Th17 responses, and ameliorates disease severity in mice.","whyItMatters":"Dry eye disease lacks targeted treatments. This study identifies substance P/NK1R as a druggable pathway that corrects the fundamental immune imbalance driving the disease.","specificNumbers":"SP ↑ in DED; SP reduced Treg frequency/function; NK1R antagonist restored Tregs; Th17 suppressed; DED ameliorated","methodology":"In vitro Treg cultures with substance P and NK1R antagonist, in vivo NK1R antagonist treatment in dry eye disease mouse model, flow cytometry for Treg and Th17 analysis.","limitations":"Mouse model of DED. NK1R antagonist effects need validation in human DED. Exact mechanism of SP-mediated Treg suppression not fully elucidated."},{"rthcId":"RPEP-05159","title":"Generation of an engineered food-grade Lactococcus lactis strain for production of an antimicrobial peptide: in vitro and in silico evaluation.","authors":"Tanhaeian, Abbas; Mirzaii, Mehdi; Pirkhezranian, Zana; Sekhavati, Mohammad Hadi","year":2020,"journal":"BMC biotechnology, 20(1), 19","doi":"10.1186/s12896-020-00612-3","pmid":"32228563","tags":["lactoferrin","antimicrobial-peptides","food-derived-peptides"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"A food-grade L. lactis strain successfully produces a chimeric lactoferrin-derived antimicrobial peptide with broad antibacterial and antibiofilm activity, stable after boiling.","whyItMatters":"With growing concerns about chemical food additives, antimicrobial peptides produced by food-grade bacteria offer a safe, natural alternative for food preservation.","specificNumbers":"0.13 mg/mL yield; antimicrobial vs foodborne bacteria; biofilm inhibition; IC50 310 µg/mL antioxidant; stable 40 min boiling","methodology":"Recombinant peptide expression in food-grade L. lactis, disk diffusion antimicrobial testing, biofilm inhibition assays, antioxidant activity (IC50), thermal stability, molecular dynamics simulation.","limitations":"In vitro testing only. Food matrix effects on peptide activity not assessed. Scale-up and regulatory approval pathways not addressed."},{"rthcId":"RPEP-05160","title":"Smart Strategies for Therapeutic Agent Delivery into Brain across the Blood-Brain Barrier Using Receptor-Mediated Transcytosis.","authors":"Tashima, Toshihiko","year":2020,"journal":"Chemical & pharmaceutical bulletin, 68(4), 316-325","doi":"10.1248/cpb.c19-00854","pmid":"32238649","tags":["cell-penetrating-peptides","drug-delivery-systems","neurological-conditions"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"RMT strategies using CPPs, targeting peptides, or antibodies that bind TfR, LDLR, or InsR on brain endothelial cells can overcome the BBB and deliver therapeutics to the brain.","whyItMatters":"The blood-brain barrier blocks most drugs from reaching the brain, limiting treatment options for Alzheimer's, Parkinson's, and other neurological diseases. RMT-based delivery could unlock therapies currently unable to reach their targets.","specificNumbers":"3 key receptors (TfR, LDLR, InsR); 3 ligand types; several clinical candidates","methodology":"Narrative review of RMT mechanisms, targeting ligand types, receptor biology, and clinical development status of BBB-crossing drug conjugates.","limitations":"Review article. Many strategies are preclinical. Achieving sufficient brain concentrations while avoiding peripheral effects remains challenging."},{"rthcId":"RPEP-05161","title":"Current knowledge on autoantigens and autoantibodies in psoriasis.","authors":"Ten Bergen, Lisa Lynn; Petrovic, Aleksandra; Aarebrot, Anders Krogh; Appel, Silke","year":2020,"journal":"Scandinavian journal of immunology, 92(4), e12945","doi":"10.1111/sji.12945","pmid":"32697368","tags":["cathelicidins","antimicrobial-peptides","immune-function"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"LL-37 and ADAMTSL5 autoantibodies are strongly associated with psoriatic arthritis, establishing psoriasis as an autoimmune disease with specific peptide autoantigens.","whyItMatters":"Identifying specific autoantigens opens the door to antigen-targeted therapies that could treat psoriasis without broadly suppressing the immune system.","specificNumbers":"4 autoantigens since 2014; autoreactive T cells; anti-LL-37 and anti-ADAMTSL5 antibodies linked to PsA","methodology":"Review of published studies on psoriasis autoantigen discovery, autoreactive T cell characterization, and autoantibody association with disease subtypes.","limitations":"Review article. The relative contribution of each autoantigen to disease initiation and maintenance is still being established."},{"rthcId":"RPEP-05162","title":"Development and Characterization of a Novel Peptide-Loaded Antimicrobial Ocular Insert.","authors":"Terreni, Eleonora; Burgalassi, Susi; Chetoni, Patrizia; Tampucci, Silvia; Zucchetti, Erica; Fais, Roberta; Ghelardi, Emilia; Lupetti, Antonella; Monti, Daniela","year":2020,"journal":"Biomolecules, 10(5)","doi":"10.3390/biom10050664","pmid":"32344824","tags":["lactoferrin","antimicrobial-peptides","drug-delivery-systems"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"A mucoadhesive freeze-dried insert formulation (HPMC/T2/HA/hLF 1-11) provides sustained release of the lactoferrin-derived antimicrobial peptide with maintained stability.","whyItMatters":"Infectious keratitis is the leading cause of blindness worldwide, and bacterial resistance makes alternative treatments urgent. An AMP-loaded eye insert avoids the compliance issues of frequent eye drops.","specificNumbers":"6 months chemical stability; 15 months antimicrobial activity; controlled release; HPMC/T2/HA matrix","methodology":"Formulation development with freeze-dried matrices, characterization of rheology, hydration time, bioadhesion, drug content, and in vitro release profiles.","limitations":"In vitro characterization only. No antimicrobial efficacy data against actual pathogens. No in vivo testing."},{"rthcId":"RPEP-05163","title":"Interrogating the Lactate Dehydrogenase Tetramerization Site Using (Stapled) Peptides.","authors":"Thabault, Léopold; Brisson, Lucie; Brustenga, Chiara; Martinez Gache, Santiago A; Prévost, Julien R C; Kozlova, Arina; Spillier, Quentin; Liberelle, Maxime; Benyahia, Zohra; Messens, Joris; Copetti, Tamara; Sonveaux, Pierre; Frédérick, Raphaël","year":2020,"journal":"Journal of medicinal chemistry, 63(9), 4628-4643","doi":"10.1021/acs.jmedchem.9b01955","pmid":"32250117","tags":["peptide-modifications","cancer-research","peptide-synthesis"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"A macrocyclic stapled peptide binds the LDH tetramerization site and competes with the natural tetramerization domain, disrupting enzyme assembly.","whyItMatters":"LDH is an important cancer target but has resisted conventional drug design. Disrupting its assembly via stapled peptides opens a completely new therapeutic approach.","specificNumbers":"Macrocyclic peptide disrupted LDH tetramers; validated by WaterLOGSY NMR and MST; dimeric model created","methodology":"Computational dimer model design, WaterLOGSY NMR screening, microscale thermophoresis binding analysis, stapled peptide synthesis.","limitations":"In vitro binding and competition data only. No cellular or in vivo efficacy demonstrated. Peptide cell permeability not assessed."},{"rthcId":"RPEP-05164","title":"Topical antimicrobial peptide formulations for wound healing: Current developments and future prospects.","authors":"Thapa, Raj Kumar; Diep, Dzung B; Tønnesen, Hanne Hjorth","year":2020,"journal":"Acta biomaterialia, 103, 52-67","doi":"10.1016/j.actbio.2019.12.025","pmid":"31874224","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05165","title":"Oxytocin and postpartum depression: A systematic review.","authors":"Thul, Taylor A; Corwin, Elizabeth J; Carlson, Nicole S; Brennan, Patricia A; Young, Larry J","year":2020,"journal":"Psychoneuroendocrinology, 120, 104793","doi":"10.1016/j.psyneuen.2020.104793","pmid":"32683141","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05166","title":"Targeting c-Myc with a novel Peptide Nuclear Delivery Device.","authors":"Ting, Trinda Anne; Chaumet, Alexandre; Bard, Frederic Andre","year":2020,"journal":"Scientific reports, 10(1), 17762","doi":"10.1038/s41598-020-73998-x","pmid":"33082422","tags":["cell-penetrating-peptides","cancer-research","drug-delivery-systems"],"studyType":"in vitro","evidenceStrength":"moderate","keyFinding":"PNDD1 delivers the c-Myc inhibitor peptide H1 to the nucleus and inhibits c-Myc-dependent transcription at nanomolar concentration, far exceeding the activity of H1 with conventional CPPs.","whyItMatters":"Many cancer targets like c-Myc are in the nucleus, but most delivery systems only reach the cytoplasm. PNDD is the first system to efficiently deliver therapeutic peptides specifically to the nucleus.","specificNumbers":"Nanomolar potency (vs µM for CPP); killed DLBCL lines; spared normal B cells; delivered GST-sized cargo to nucleus","methodology":"Fusion protein construction, nuclear localization tracking, c-Myc transcription inhibition assays, comparison with CPP-conjugated controls.","limitations":"In vitro proof-of-concept. Immunogenicity of the bacterial exotoxin fragment needs assessment. In vivo delivery efficiency unknown."},{"rthcId":"RPEP-05167","title":"Early phase II study of mixed 19-peptide vaccine monotherapy for refractory triple-negative breast cancer.","authors":"Toh, Uhi; Sakurai, Sayaka; Saku, Shuko; Takao, Yuko; Okabe, Mina; Iwakuma, Nobutaka; Shichijo, Shigeki; Yamada, Akira; Itoh, Kyogo; Akagi, Yoshito","year":2020,"journal":"Cancer science, 111(8), 2760-2769","doi":"10.1111/cas.14510","pmid":"32495455","tags":["cancer-research","clinical-applications","immune-function"],"studyType":"clinical trial","evidenceStrength":"preliminary","keyFinding":"Peptide-specific IgG responses correlated with overall survival (P < .01), and median OS was 24.4 months in the 10 patients who completed vaccination — notable for refractory mTNBC.","whyItMatters":"Triple-negative breast cancer has the worst prognosis and fewest treatment options. A 24.4-month median survival in refractory patients is remarkable for this population.","specificNumbers":"n=14; 19 peptides; weekly x 6 weeks; mOS 11.5 mo (all) / 24.4 mo (10 completers); IgG-OS correlation p<0.01; no severe AEs","methodology":"Phase II single-arm clinical trial, 14 patients, weekly vaccination for 6 weeks, immune response monitoring via peptide-specific IgG, survival analysis.","limitations":"Very small single-arm trial (14 patients) without a control group. Selection bias in the completer analysis. Early phase data."},{"rthcId":"RPEP-05168","title":"Nasal absorption enhancement of protein drugs independent to their chemical properties in the presence of hyaluronic acid modified with tetraglycine-L-octaarginine.","authors":"Tomono, Takumi; Yagi, Haruya; Ukawa, Masami; Ishizaki, Seiya; Miwa, Takahiro; Nonomura, Mao; Igi, Ryoji; Kumagai, Hironori; Miyata, Kohei; Tobita, Etsuo; Kobayashi, Hideo; Sakuma, Shinji","year":2020,"journal":"European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 154, 186-194","doi":"10.1016/j.ejpb.2020.07.003","pmid":"32681963","tags":["cell-penetrating-peptides","drug-delivery-systems","glp-1-receptor-agonists"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"Hyaluronic acid modified with octaarginine enables nasal absorption of protein drugs with ~20% bioavailability, independent of the drug's chemical properties, matching the SNAC enhancer used in oral semaglutide.","whyItMatters":"Most peptide drugs require injection. A nasal delivery system achieving 20% bioavailability could transform patient experience for GLP-1 and other peptide medications.","specificNumbers":"~20% BA exenatide; 5x ↑ somatropin; equivalent to SNAC for small peptides; charge-independent; 4 drugs tested (1-22 kDa)","methodology":"Mouse nasal absorption studies comparing HA-octaarginine carrier with SNAC and unformulated protein drugs, measuring bioavailability relative to subcutaneous injection.","limitations":"Mouse study — nasal anatomy and absorption differ from humans. Long-term nasal safety not assessed. Regulatory pathway unclear."},{"rthcId":"RPEP-05169","title":"The wasp venom antimicrobial peptide polybia-CP and its synthetic derivatives display antiplasmodial and anticancer properties.","authors":"Torres, Marcelo D T; Silva, Adriana F; Andrade, Gislaine P; Pedron, Cibele N; Cerchiaro, Giselle; Ribeiro, Anderson O; Oliveira, Vani X; de la Fuente-Nunez, Cesar","year":2020,"journal":"Bioengineering & translational medicine, 5(3), e10167","doi":"10.1002/btm2.10167","pmid":"33005737","tags":["venom-derived-peptides","antimicrobial-peptides","cancer-research"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Polybia-CP derivatives with optimized helicity and charge show potent antiplasmodial and anticancer activity while having reduced general toxicity compared to the wild-type peptide.","whyItMatters":"Malaria kills hundreds of thousands annually and drug resistance is growing. Antimicrobial peptides with antiplasmodial activity represent a new drug class with a different mechanism of action.","specificNumbers":"Submicromolar antiplasmodial potency; micromolar anticancer; helicity + charge drive activity; hydrophobicity needed for cancer","methodology":"Physicochemical-guided peptide design, antiplasmodial activity against Plasmodium sporozoites, cancer cell killing assays, structure-activity analysis.","limitations":"In vitro activity data only. Selectivity between parasite/cancer cells and host cells needs further optimization. No in vivo efficacy data."},{"rthcId":"RPEP-05170","title":"Metabolic insights from a GHSR-A203E mutant mouse model.","authors":"Torz, Lola J; Osborne-Lawrence, Sherri; Rodriguez, Juan; He, Zhenyan; Cornejo, María Paula; Mustafá, Emilio Román; Jin, Chunyu; Petersen, Natalia; Hedegaard, Morten A; Nybo, Maja; Damonte, Valentina Martínez; Metzger, Nathan P; Mani, Bharath K; Williams, Kevin W; Raingo, Jesica; Perello, Mario; Holst, Birgitte; Zigman, Jeffrey M","year":2020,"journal":"Molecular metabolism, 39, 101004","doi":"10.1016/j.molmet.2020.101004","pmid":"32339772","tags":["ghrelin","appetite-regulation","neurological-conditions"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"Eliminating ghrelin receptor constitutive activity in mice reveals that baseline GHSR signaling, independent of ghrelin, contributes to metabolic regulation and may explain some effects previously attributed to ghrelin itself.","whyItMatters":"Understanding constitutive GHSR activity is crucial for developing ghrelin-based therapies. Drugs targeting only ghrelin binding may miss important metabolic effects driven by the receptor's baseline activity.","specificNumbers":"Reduced baseline IP3; hyperpolarized NPY neurons; ghrelin response preserved; no body weight/length difference at ~6 months","methodology":"GHSR-A203E knock-in mouse generation, ex vivo neuronal electrophysiology, in vivo metabolic phenotyping, comparison with wild-type mice.","limitations":"Mouse model — human metabolic effects may differ. The A203E mutation affects both constitutive and ghrelin-dependent signaling pathways."},{"rthcId":"RPEP-05171","title":"Enzymatic Ligation of a Pore Blocker Toxin and a Gating Modifier Toxin: Creating Double-Knotted Peptides with Improved Sodium Channel NaV1.7 Inhibition.","authors":"Tran, Hue N T; Tran, Poanna; Deuis, Jennifer R; Agwa, Akello J; Zhang, Alan H; Vetter, Irina; Schroeder, Christina I","year":2020,"journal":"Bioconjugate chemistry, 31(1), 64-73","doi":"10.1021/acs.bioconjchem.9b00744","pmid":"31790574","tags":["venom-derived-peptides","ion-channels","pain-management"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Enzymatic ligation of two venom peptides targeting different NaV1.7 binding sites creates a bivalent inhibitor with enhanced sodium channel blockade.","whyItMatters":"NaV1.7 is a genetically validated pain target, but single-site inhibitors haven't achieved sufficient clinical efficacy. Bivalent inhibitors hitting two sites simultaneously could finally unlock this target.","specificNumbers":"9-AA optimal linker; improved affinity/potency vs PaurTx3 or KIIIA alone; sortase A ligation","methodology":"Evolved sortase A-mediated enzymatic ligation, electrophysiology for NaV1.7 inhibition measurement, structural characterization of double-knotted peptides.","limitations":"In vitro electrophysiology data only. In vivo pain relief not demonstrated. Manufacturing complexity of double-knotted peptides may limit clinical development."},{"rthcId":"RPEP-05172","title":"Automated Flow Synthesis of Tumor Neoantigen Peptides for Personalized Immunotherapy.","authors":"Truex, Nicholas L; Holden, Rebecca L; Wang, Bin-You; Chen, Pu-Guang; Hanna, Stephanie; Hu, Zhuting; Shetty, Keerthi; Olive, Oriol; Neuberg, Donna; Hacohen, Nir; Keskin, Derin B; Ott, Patrick A; Wu, Catherine J; Pentelute, Bradley L","year":2020,"journal":"Scientific reports, 10(1), 723","doi":"10.1038/s41598-019-56943-5","pmid":"31959774","tags":["peptide-synthesis","cancer-research","clinical-applications"],"studyType":"methods paper","evidenceStrength":"moderate","keyFinding":"Automated flow synthesis produces 30-mer cancer neoantigen peptides in under 35 minutes with clinical-grade quality, enabling rapid personalized vaccine manufacturing.","whyItMatters":"Personalized cancer vaccines are limited by the time needed to manufacture peptides for each patient. Reducing synthesis from days to minutes could make these therapies clinically practical.","specificNumbers":"30-mer in <35 min; 15-16-mer in <20 min; purity comparable/superior to conventional","methodology":"Automated flow peptide synthesis with HPLC quality analysis, production of patient-specific neoantigen peptides identified from tumor sequencing data.","limitations":"Methods paper focused on synthesis speed and quality. Clinical efficacy of the resulting vaccines not assessed here."},{"rthcId":"RPEP-05173","title":"Safety and tolerability of once-weekly GLP-1 receptor agonists in type 2 diabetes.","authors":"Trujillo, Jennifer","year":2020,"journal":"Journal of clinical pharmacy and therapeutics, 45 Suppl 1(Suppl 1), 43-60","doi":"10.1111/jcpt.13225","pmid":"32910487","tags":["glp-1-receptor-agonists","diabetes","clinical-applications"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Once-weekly GLP-1 RAs have manageable safety profiles dominated by gastrointestinal side effects, with differences between agents that inform treatment selection.","whyItMatters":"With GLP-1 RAs increasingly prescribed for diabetes and obesity, clinicians need clear safety comparisons to choose the right agent for each patient.","specificNumbers":"30 trials; 3 QW GLP-1 RAs; GI AEs most common; semaglutide DRC 3.0% vs 1.8% placebo (SUSTAIN 6); low hypoglycemia/pancreatitis/neoplasm rates","methodology":"Narrative review comparing phase 3 clinical trial safety data for dulaglutide, exenatide ER, and semaglutide.","limitations":"Based on clinical trial data which may not capture all real-world safety signals. Head-to-head comparisons between agents are limited."},{"rthcId":"RPEP-05174","title":"Altering Antigen Charge to Control Self-Assembly and Processing of Immune Signals During Cancer Vaccination.","authors":"Tsai, Shannon J; Amerman, Allie; Jewell, Christopher M","year":2020,"journal":"Frontiers in immunology, 11, 613830","doi":"10.3389/fimmu.2020.613830","pmid":"33488621","tags":["cancer-research","drug-delivery-systems","immune-function"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Arginine-modified melanoma peptide self-assembles with CpG adjuvant into nanoparticles that enhance antigen presentation and slow tumor growth in mice.","whyItMatters":"This simple charge-based self-assembly eliminates the need for complex polymer delivery systems, making cancer vaccines easier to formulate.","specificNumbers":"Arg-modified Trp2 + CpG polyplexes; improved APC uptake; enhanced T cells; reduced tumors; improved survival","methodology":"Peptide modification with arginine residues, nanoparticle characterization, antigen uptake by primary APCs, mouse tumor growth studies.","limitations":"Single antigen model (Trp2). Mouse melanoma model may not translate to human cancer. Immune response characterization is limited."},{"rthcId":"RPEP-05175","title":"Human antimicrobial peptides in autoimmunity.","authors":"Umnyakova, Ekaterina S; Zharkova, Maria S; Berlov, Mikhail N; Shamova, Olga V; Kokryakov, Vladimir N","year":2020,"journal":"Autoimmunity, 53(3), 137-147","doi":"10.1080/08916934.2020.1711517","pmid":"31914804","tags":["antimicrobial-peptides","immune-function","defensins"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Human AMPs have dual roles in autoimmune diseases — they can both promote inflammation (e.g., LL-37 in psoriasis) and suppress it (e.g., defensins in some contexts), depending on the disease and immune environment.","whyItMatters":"Understanding the dual nature of AMPs in autoimmunity is essential for developing therapies that can selectively modulate their pro- or anti-inflammatory effects.","specificNumbers":"6 autoimmune diseases reviewed; dual pro/anti-inflammatory roles; complement modulation identified","methodology":"Narrative review of published literature on AMP involvement in six major autoimmune disorders.","limitations":"Review article. The complex, context-dependent roles of AMPs make simple therapeutic targeting challenging."},{"rthcId":"RPEP-05176","title":"Long-acting GLP-1 receptor agonists: Findings and implications of cardiovascular outcomes trials.","authors":"Urquhart, Scott; Willis, Stephen","year":2020,"journal":"JAAPA : official journal of the American Academy of Physician Assistants, 33(S8 Suppl 1), 19-30","doi":"10.1097/01.JAA.0000669452.63883.45","pmid":"32756221","tags":["glp-1-receptor-agonists","cardiovascular-health","diabetes","clinical-applications"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Long-acting GLP-1 RAs are cardiovascularly safe, with liraglutide, semaglutide, and dulaglutide demonstrating significant cardiovascular risk reduction in outcome trials.","whyItMatters":"Cardiovascular disease is the leading cause of death in T2D patients. GLP-1 RAs that reduce cardiovascular events while lowering blood sugar address both conditions simultaneously.","specificNumbers":"6 GLP-1 RAs; all noninferior for MACE; 3 significantly reduced MACE; FDA label updates for 3 drugs","methodology":"Review of completed cardiovascular outcome trials for all long-acting GLP-1 RAs, analyzing major adverse cardiovascular event (MACE) endpoints.","limitations":"CVOT designs vary between agents, making direct comparisons difficult. Most trials studied high-CV-risk populations."},{"rthcId":"RPEP-05177","title":"Liraglutide improves memory in obese patients with prediabetes or early type 2 diabetes: a randomized, controlled study.","authors":"Vadini, Francesco; Simeone, Paola G; Boccatonda, Andrea; Guagnano, Maria T; Liani, Rossella; Tripaldi, Romina; Di Castelnuovo, Augusto; Cipollone, Francesco; Consoli, Agostino; Santilli, Francesca","year":2020,"journal":"International journal of obesity (2005), 44(6), 1254-1263","doi":"10.1038/s41366-020-0535-5","pmid":"31965072","tags":["glp-1-receptor-agonists","neuroprotection","diabetes"],"studyType":"randomized controlled trial","evidenceStrength":"moderate","keyFinding":"Liraglutide improved cognitive function in the memory domain in obese patients with prediabetes or early T2D, independent of weight loss effects.","whyItMatters":"Diabetic patients face increased dementia risk. If GLP-1 drugs protect cognition beyond metabolic benefits, this adds another major reason to prescribe them early.","specificNumbers":"n=40 (16/arm completed); Digit Span p=0.024; memory composite p=0.0065; between-group p=0.041/0.033; matched 7% weight loss","methodology":"Randomized controlled trial, 40 subjects, liraglutide vs lifestyle intervention, 26 weeks, cognitive testing.","limitations":"Small sample (40 patients). Short duration (26 weeks). Open-label design. Single-center study."},{"rthcId":"RPEP-05178","title":"Mechanism of bariatric and metabolic surgery: beyond surgeons, gastroenterologists and endocrinologists.","authors":"Valentí, Víctor; Cienfuegos, Javier A; Becerril Mañas, Sara; Frühbeck, Gema","year":2020,"journal":"Revista espanola de enfermedades digestivas, 112(3), 229-233","doi":"10.17235/reed.2020.6925/2020","pmid":"32081018","tags":["glp-1-receptor-agonists","ghrelin","gut-peptides","appetite-regulation"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Bariatric surgery's metabolic benefits are mediated by altered gut peptide hormone secretion, particularly increased GLP-1 and PYY, rather than simple caloric restriction.","whyItMatters":"Understanding the hormonal mechanism behind bariatric surgery's success guides development of medications that replicate these effects without surgery.","specificNumbers":"GLP-1 ↑, PYY ↑, ghrelin ↓ post-surgery; bile acid and microbiome changes; weight-independent metabolic benefits","methodology":"Narrative review of gut peptide physiology changes after various bariatric procedures.","limitations":"Review article. Exact hormonal mechanisms vary between surgical procedures and patients."},{"rthcId":"RPEP-05179","title":"A Method to Calculate the Relative Binding Free Energy Differences of α-Helical Stapled Peptides.","authors":"Valiente, Pedro A; Becerra, David; Kim, Philip M","year":2020,"journal":"The Journal of organic chemistry, 85(3), 1644-1651","doi":"10.1021/acs.joc.9b03067","pmid":"31893470","tags":["peptide-modifications","peptide-synthesis","cancer-research"],"studyType":"computational","evidenceStrength":"preliminary","keyFinding":"The free energy perturbation-based protocol accurately predicts relative binding free energies for different stapled peptide variants, enabling rational staple position selection.","whyItMatters":"Stapled peptides are promising drugs for disrupting protein-protein interactions in cancer and other diseases, but choosing where to place the staple has been guesswork. This method makes the process rational.","specificNumbers":"Accurate affinity rank-ordering; hot-spot prediction; staple effects on neighboring residues; perfluoroarene stapled peptides","methodology":"Molecular dynamics simulations, free energy perturbation calculations, validation against experimentally measured binding affinities.","limitations":"Computational predictions require experimental validation. Method accuracy depends on force field quality and sampling adequacy."},{"rthcId":"RPEP-05180","title":"Human platelets and megakaryocytes express defensin alpha 1.","authors":"Valle-Jiménez, Xareni; Ramírez-Cosmes, Adriana; Aquino-Domínguez, Alba Soledad; Sánchez-Peña, Francisco; Bustos-Arriaga, José; Romero-Tlalolini, María De Los Ángeles; Torres-Aguilar, Honorio; Serafín-López, Jeanet; Aguilar Ruíz, Sergio Roberto","year":2020,"journal":"Platelets, 31(3), 344-354","doi":"10.1080/09537104.2019.1615612","pmid":"31116063","tags":["defensins","antimicrobial-peptides","immune-function"],"studyType":"in vitro","evidenceStrength":"moderate","keyFinding":"Human platelets and megakaryocytes express defensin alpha 1, adding to the antimicrobial peptide repertoire of these blood cells.","whyItMatters":"Platelets are the most abundant circulating immune-active cells. Understanding their full antimicrobial peptide production informs how the blood fights infections.","specificNumbers":"DEFA1 in alpha-granules; secreted by thrombin/ADP/LPS; kills E. coli; mRNA transferred from megakaryocytes to PLPs","methodology":"Gene expression analysis, immunodetection, and secretion assays in human platelets and megakaryocyte cell lines.","limitations":"In vitro study. The functional significance of platelet DEFA1 in vivo infection defense remains to be established."},{"rthcId":"RPEP-05181","title":"Down-Regulation of Collagen Hydroxylation in Colorectal Liver Metastasis.","authors":"van Huizen, Nick A; Burgers, Peter C; van Rosmalen, Joost; Doukas, Michail; IJzermans, Jan N M; Luider, Theo M","year":2020,"journal":"Frontiers in oncology, 10, 557737","doi":"10.3389/fonc.2020.557737","pmid":"33117689","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05182","title":"Corticotropin-releasing factor receptor signaling and modulation: implications for stress response and resilience.","authors":"Vasconcelos, Mailton; Stein, Dirson J; Gallas-Lopes, Matheus; Landau, Luane; de Almeida, Rosa Maria M","year":2020,"journal":"Trends in psychiatry and psychotherapy, 42(2), 195-206","doi":"10.1590/2237-6089-2018-0027","pmid":"32696892","tags":["neuropeptides","mental-health","stress-response"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"CRF family peptides and their two receptor subtypes mediate stress responses across multiple organ systems, with dysregulation conferring vulnerability to psychiatric and physical disorders.","whyItMatters":"Chronic stress underlies many psychiatric and physical conditions. Understanding CRF peptide signaling provides targets for treatments that enhance stress resilience.","specificNumbers":"CRF1 and CRF2 receptors; CRF + 3 urocortins; CRF-BP; multiple G-protein pathways; roles in 6+ organ systems","methodology":"Narrative review of CRF/urocortin signaling, receptor pharmacology, and implications for stress-related disease.","limitations":"Review of a complex system with sometimes contradictory findings across species and experimental conditions."},{"rthcId":"RPEP-05183","title":"Angiotensin Receptor-Neprilysin Inhibitors and the Natriuretic Peptide Axis.","authors":"Vasquez, Nestor; Carter, Spencer; Grodin, Justin L","year":2020,"journal":"Current heart failure reports, 17(3), 67-76","doi":"10.1007/s11897-020-00458-y","pmid":"32394149","tags":["natriuretic-peptides","cardiovascular-health","clinical-applications"],"studyType":"review","evidenceStrength":"strong","keyFinding":"ARNI therapy boosts BNP, ANP, and CNP levels through neprilysin inhibition, explaining its superior outcomes in HFrEF through enhanced natriuretic peptide-mediated cardioprotection.","whyItMatters":"Understanding how ARNI therapy works through natriuretic peptides helps clinicians optimize treatment and researchers develop next-generation heart failure therapies.","specificNumbers":"BNP ↑, NT-proBNP ↓, ANP ↑, CNP unchanged; both BNP/NT-proBNP retain prognostic accuracy; correlate with echo improvement","methodology":"Review of natriuretic peptide biology, neprilysin pharmacology, and ARNI clinical trial data.","limitations":"Review focused on natriuretic peptides — ARNI also affects other neprilysin substrates which may contribute to its effects."},{"rthcId":"RPEP-05184","title":"Peptide-Conjugated Phosphorodiamidate Morpholino Oligomers for In Situ Live-Cell Molecular Imaging of Dengue Virus Replication.","authors":"Victorio, Carla Bianca Luena; Novera, Wisna; Tham, Jing Yang; Watanabe, Satoru; Vasudevan, Subhash G; Chacko, Ann-Marie","year":2020,"journal":"International journal of molecular sciences, 21(23)","doi":"10.3390/ijms21239260","pmid":"33291644","tags":["cell-penetrating-peptides","drug-delivery-systems"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"CPP-conjugated morpholino oligomers enable in situ live-cell molecular imaging of dengue virus replication, providing both spatial and temporal information simultaneously.","whyItMatters":"Current pathogen detection methods sacrifice either spatial context or temporal detail. This CPP-based approach provides both, enabling better understanding of viral biology.","specificNumbers":"PPMOs targeting DENV2; unsuitable for live-cell imaging; adequate as antivirals; cautionary negative result","methodology":"Antisense morpholino probe design targeting dengue viral RNA, CPP conjugation for cell delivery, live-cell imaging microscopy.","limitations":"Proof-of-concept for dengue virus specifically. Signal specificity and sensitivity need further optimization. Not yet validated for other viruses."},{"rthcId":"RPEP-05185","title":"Age-related molecular changes in the lumbar dorsal root ganglia of mice: Signs of sensitization, and inflammatory response.","authors":"Vincent, Kathleen; Dona, Chethana Prabodhanie Gallage; Albert, Todd J; Dahia, Chitra Lekha","year":2020,"journal":"JOR spine, 3(4), e1124","doi":"10.1002/jsp2.1124","pmid":"33392459","tags":["cgrp","substance-p","neuropeptides","pain-management"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"Chronological aging increases CGRP and substance P in lumbar DRG neurons, with concurrent signs of sensitization and inflammation that parallel disc degeneration.","whyItMatters":"Back pain is extremely common in aging populations but its molecular mechanisms are poorly understood. This study connects neuropeptide changes in sensory neurons to age-related disc degeneration.","specificNumbers":"Calca/ATF3/BDNF ↑ linearly from 12mo; TAC1 protein ↑ 24mo; Nfkb1/Rela ↑; TNF/IL-6/IL-1β/COX-2 unchanged","methodology":"Age-series mouse study with molecular analysis of neuropeptide expression, inflammatory markers, and sensitization indicators in lumbar DRG neurons.","limitations":"Mouse study — aging patterns may differ in humans. Correlative data cannot establish causation between neuropeptide changes and pain."},{"rthcId":"RPEP-05186","title":"The effect of pentadecapeptide BPC 157 on hippocampal ischemia/reperfusion injuries in rats.","authors":"Vukojević, Jakša; Vrdoljak, Borna; Malekinušić, Dominik; Siroglavić, Marko; Milavić, Marija; Kolenc, Danijela; Boban Blagaić, Alenka; Batelja, Lovorka; Drmić, Domagoj; Seiverth, Sven; Sikirić, Predrag","year":2020,"journal":"Brain and behavior, 10(8), e01726","doi":"10.1002/brb3.1726","pmid":"32558293","tags":["bpc-157","neuroprotection","wound-healing"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"BPC-157 reduces hippocampal ischemia/reperfusion injury in rats by counteracting oxidative stress and restoring blood vessel function during reperfusion.","whyItMatters":"Brain ischemia/reperfusion injury occurs in stroke and cardiac arrest. BPC-157's neuroprotective effects could be relevant for developing treatments that limit brain damage after blood flow restoration.","specificNumbers":"10 mcg/kg topical; 20-min ischemia; full recovery 24-72h; Egr1/Akt1/Vegfr2/eNOS ↑; iNOS/NF-kB ↓","methodology":"Bilateral common carotid artery clamping in rats, BPC-157 administration during reperfusion, histological and functional assessments.","limitations":"Animal study with a single injury model. BPC-157's mechanism is not fully understood. Translation to human stroke therapy is speculative."},{"rthcId":"RPEP-05187","title":"Influence of cell-penetrating peptides on the activity and stability of virus-based nanoparticles.","authors":"Váňová, Jana; Hejtmánková, Alžběta; Žáčková Suchanová, Jiřina; Sauerová, Pavla; Forstová, Jitka; Hubálek Kalbáčová, Marie; Španielová, Hana","year":2020,"journal":"International journal of pharmaceutics, 576, 119008","doi":"10.1016/j.ijpharm.2019.119008","pmid":"31901358","tags":["cell-penetrating-peptides","drug-delivery-systems","gene-therapy"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"CPPs enhance viral nanoparticle gene delivery efficiency, with different CPP types showing distinct effects on nanoparticle activity and stability.","whyItMatters":"Viral gene therapy vectors often have limited efficiency. CPPs could boost their performance, making gene therapy more effective at lower doses.","specificNumbers":"3/4 CPPs enhanced; R8 destabilized; KH27K aggregated; LAH4 disassembled; FUSO no effect; HS-independent","methodology":"In vitro gene transfer assays with four different CPPs conjugated to viral nanoparticles, stability assessments.","limitations":"In vitro study. CPP-vector interactions may differ in vivo. Immunogenicity and toxicity not assessed."},{"rthcId":"RPEP-05188","title":"CD4/CD8 ratio is a prognostic factor in IgG nonresponders among peptide vaccine-treated ovarian cancer patients.","authors":"Waki, Kayoko; Kawano, Kouichiro; Tsuda, Naotake; Komatsu, Nobukazu; Yamada, Akira","year":2020,"journal":"Cancer science, 111(4), 1124-1131","doi":"10.1111/cas.14349","pmid":"32058620","tags":["cancer-research","immune-function","biomarkers"],"studyType":"clinical trial","evidenceStrength":"preliminary","keyFinding":"The CD4/CD8 T cell ratio is a prognostic factor for IgG nonresponders among peptide vaccine-treated ovarian cancer patients, identifying survivors who benefit despite no antibody response.","whyItMatters":"Identifying biomarkers for patients who benefit from immunotherapy without traditional response markers is crucial for treatment decisions and avoiding premature treatment cessation.","specificNumbers":"n=25 IgG nonresponders; ↑CD8 (n=7) vs ↓CD8 (n=18) p=0.018; ↓CD4/CD8 (n=10) vs ↑ (n=15) p=0.0055","methodology":"Retrospective analysis of ovarian cancer patients treated with personalized peptide vaccination, biomarker analysis of IgG nonresponders.","limitations":"Retrospective analysis with limited sample size. The CD4/CD8 ratio is a general immune marker, not specific to tumor-reactive T cells."},{"rthcId":"RPEP-05189","title":"Chlorotoxin-directed CAR T cells for specific and effective targeting of glioblastoma.","authors":"Wang, Dongrui; Starr, Renate; Chang, Wen-Chung; Aguilar, Brenda; Alizadeh, Darya; Wright, Sarah L; Yang, Xin; Brito, Alfonso; Sarkissian, Aniee; Ostberg, Julie R; Li, Li; Shi, Yanhong; Gutova, Margarita; Aboody, Karen; Badie, Behnam; Forman, Stephen J; Barish, Michael E; Brown, Christine E","year":2020,"journal":"Science translational medicine, 12(533)","doi":"10.1126/scitranslmed.aaw2672","pmid":"32132216","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05190","title":"Delivery of MSCs with a Hybrid β-Sheet Peptide Hydrogel Consisting IGF-1C Domain and D-Form Peptide for Acute Kidney Injury Therapy.","authors":"Wang, Hongfeng; Shang, Yuna; Chen, Xiaoniao; Wang, Zhongyan; Zhu, Dashuai; Liu, Yue; Zhang, Chuyue; Chen, Pu; Wu, Jie; Wu, Lingling; Kong, Deling; Yang, Zhimou; Li, Zongjin; Chen, Xiangmei","year":2020,"journal":"International journal of nanomedicine, 15, 4311-4324","doi":"10.2147/IJN.S254635","pmid":"32606679","tags":["igf-1","drug-delivery-systems","wound-healing"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"An IGF-1C domain peptide hydrogel with D-amino acid stability enhancement improves MSC survival, engraftment, and therapeutic efficacy in acute kidney injury.","whyItMatters":"Stem cell therapy for kidney injury is limited by poor cell survival after transplantation. This peptide hydrogel solves that problem by creating a protective microenvironment.","specificNumbers":"IGF-1C domain; D-form peptide; β-sheet self-assembly; enhanced angiogenesis; kidney function recovery","methodology":"Self-assembling peptide hydrogel synthesis, MSC encapsulation and delivery, acute kidney injury mouse/rat model, histological and functional kidney assessments.","limitations":"Animal study. Long-term fate of MSCs in hydrogel not assessed. Translation to human kidney injury treatment needs clinical validation."},{"rthcId":"RPEP-05191","title":"Design, Synthesis, and Antitumor Activities Study of Stapled A4K14-Citropin 1.1 Peptides.","authors":"Wang, Nan; Xie, Gang; Liu, Chao; Cong, Wei; He, Shipeng; Li, Yinghua; Fan, Li; Hu, Hong-Gang","year":2020,"journal":"Frontiers in chemistry, 8, 616147","doi":"10.3389/fchem.2020.616147","pmid":"33363118","tags":["antimicrobial-peptides","cancer-research","peptide-modifications"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Hydrocarbon stapling of A4K14-citropin 1.1 improved structural stability and enhanced antitumor activity compared to the linear parent peptide.","whyItMatters":"Many antimicrobial peptides have anticancer potential but are too flexible and unstable for therapeutic use. Stapling solves these problems while potentially improving activity.","specificNumbers":"Sp1 and Sp4 leads; improved helicity; greater protease stability; increased antitumor activity vs parent","methodology":"All-hydrocarbon stapled peptide synthesis, circular dichroism for structural analysis, antitumor activity assays against cancer cell lines.","limitations":"In vitro study only. Selectivity between cancer cells and normal cells not thoroughly assessed. No in vivo data."},{"rthcId":"RPEP-05192","title":"Antioxidant Peptides from Collagen Hydrolysate of Redlip Croaker (Pseudosciaena polyactis) Scales: Preparation, Characterization, and Cytoprotective Effects on H2O2-Damaged HepG2 Cells.","authors":"Wang, Wan-Yi; Zhao, Yu-Qin; Zhao, Guo-Xu; Chi, Chang-Feng; Wang, Bin","year":2020,"journal":"Marine drugs, 18(3)","doi":"10.3390/md18030156","pmid":"32168851","tags":["collagen-peptides","bioactive-peptides","food-derived-peptides"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Collagen peptides from redlip croaker scales, particularly the neutrase hydrolysate, show strong antioxidant activity and cytoprotective effects on liver cells.","whyItMatters":"Fish scale waste is an abundant, underutilized resource. Converting it to bioactive peptides creates value while providing natural antioxidants for food and health applications.","specificNumbers":"6 peptides (526-886 Da); EC50 0.33-0.74 mg/mL; protected HepG2; ↓ROS/MDA; ↑SOD/CAT/GSH-Px; neutrase 21.4% hydrolysis","methodology":"Enzymatic hydrolysis with six proteases, antioxidant activity assays (DPPH, hydroxyl radical scavenging), peptide characterization, HepG2 cell protection assays.","limitations":"In vitro study. The bioavailability and stability of these peptides after oral consumption need to be assessed."},{"rthcId":"RPEP-05193","title":"Composite probiotics alleviate type 2 diabetes by regulating intestinal microbiota and inducing GLP-1 secretion in db/db mice.","authors":"Wang, Yanming; Dilidaxi, Dinareer; Wu, Yuche; Sailike, Jialehasibieke; Sun, Xin; Nabi, Xin-Hua","year":2020,"journal":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 125, 109914","doi":"10.1016/j.biopha.2020.109914","pmid":"32035395","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05194","title":"Functional tumor specific CD8 + T cells in spleen express a high level of PD-1.","authors":"Wang, Zili; Chen, Ting; Lin, Wanzun; Zheng, Weili; Chen, Junying; Huang, Fei; Xie, Xianhe","year":2020,"journal":"International immunopharmacology, 80, 106242","doi":"10.1016/j.intimp.2020.106242","pmid":"32014811","tags":["cancer-immunotherapy","immune-system"],"studyType":"animal","evidenceStrength":"preliminary","keyFinding":"Splenic tumor-specific CD8 T cells activated by peptide vaccination express high PD-1 but remain functional, and PD-1 blockade enhances their anti-tumor activity.","whyItMatters":"This reframes PD-1 as an activation marker (not just exhaustion marker) in lymphoid tissues, supporting the combination of peptide vaccines with checkpoint inhibitors.","specificNumbers":"PD-1 blockade significantly enhanced cytotoxic activity of splenic CD8 T cells.","methodology":"Mouse tumor model with peptide epitope vaccination, flow cytometry for PD-1 and functional markers, PD-1 blockade antibody treatment.","limitations":"Mouse tumor model. The relationship between PD-1 expression and T cell function may differ in human cancer patients."},{"rthcId":"RPEP-05195","title":"Key Parameters of Tumor Epitope Immunogenicity Revealed Through a Consortium Approach Improve Neoantigen Prediction.","authors":"Wells, Daniel K; van Buuren, Marit M; Dang, Kristen K; Hubbard-Lucey, Vanessa M; Sheehan, Kathleen C F; Campbell, Katie M; Lamb, Andrew; Ward, Jeffrey P; Sidney, John; Blazquez, Ana B; Rech, Andrew J; Zaretsky, Jesse M; Comin-Anduix, Begonya; Ng, Alphonsus H C; Chour, William; Yu, Thomas V; Rizvi, Hira; Chen, Jia M; Manning, Patrice; Steiner, Gabriela M; Doan, Xengie C; Merghoub, Taha; Guinney, Justin; Kolom, Adam; Selinsky, Cheryl; Ribas, Antoni; Hellmann, Matthew D; Hacohen, Nir; Sette, Alessandro; Heath, James R; Bhardwaj, Nina; Ramsdell, Fred; Schreiber, Robert D; Schumacher, Ton N; Kvistborg, Pia; Defranoux, Nadine A","year":2020,"journal":"Cell, 183(3), 818-834.e13","doi":"10.1016/j.cell.2020.09.015","pmid":"33038342","tags":["cancer-immunotherapy","immune-system"],"studyType":"in_vitro","evidenceStrength":"strong","keyFinding":"An integrated model combining peptide presentation and recognition features filtered out 98% of non-immunogenic peptides with precision above 0.70, and was validated in an independent cohort of 310 epitopes.","whyItMatters":"Personalized cancer vaccines depend on correctly identifying which tumor mutations will provoke an immune response. This consortium-derived model dramatically improves neoantigen prediction, potentially making immunotherapy more targeted and effective.","specificNumbers":"608 epitopes assessed; ~8% confirmed immunogenic; peptide-MHC stability identified as top predictor.","methodology":"Global consortium where participants predicted immunogenic epitopes from shared tumor sequencing data. 608 epitopes were assessed for T cell binding in patient-matched samples, with validation in an independent 310-epitope cohort.","limitations":"The model was developed and validated using specific tumor types and HLA alleles, which may limit generalizability. T cell binding assays measure recognition potential but don't guarantee clinical anti-tumor responses."},{"rthcId":"RPEP-05196","title":"Rational design of cell-permeable cyclic peptides containing a d-Pro-l-Pro motif.","authors":"Wen, Jin; Liao, Hui; Stachowski, Kye; Hempfling, Jordan P; Qian, Ziqing; Yuan, Chunhua; Foster, Mark P; Pei, Dehua","year":2020,"journal":"Bioorganic & medicinal chemistry, 28(20), 115711","doi":"10.1016/j.bmc.2020.115711","pmid":"33069067","tags":["peptide-chemistry","drug-delivery"],"studyType":"in_vitro","evidenceStrength":"preliminary","keyFinding":"The d-Pro-l-Pro motif permitted rational design of cell-permeable cyclic peptides up to 16 amino acids in ring size, including a biologically active inhibitor of the Grb2 SH2 domain.","whyItMatters":"Many important drug targets are inside cells and currently undruggable by peptides. This design strategy could unlock a new class of peptide therapeutics capable of reaching intracellular protein-protein interaction targets.","specificNumbers":"Cyclic CPP with d-Pro-l-Pro motif achieved efficient cell entry and maintained binding affinity.","methodology":"Peptide synthesis and screening for cell-penetrating properties, followed by multidimensional NMR spectroscopy and circular dichroism analysis of peptide structures. Biological activity confirmed via Grb2 SH2 domain binding assays.","limitations":"Demonstrated primarily in cell culture systems. In vivo pharmacokinetics, stability, and therapeutic efficacy remain to be established. The approach may not work equally well for all cargo types or target proteins."},{"rthcId":"RPEP-05197","title":"Exendin-4 enhances the sensitivity of prostate cancer to enzalutamide by targeting Akt activation.","authors":"Wenjing, He; Shao, Yuanyuan; Yu, Yi; Huang, Wei; Feng, Guoliang; Li, Junhe","year":2020,"journal":"The Prostate, 80(5), 367-375","doi":"10.1002/pros.23951","pmid":"31967357","tags":["glp-1-receptor-agonists","cancer-immunotherapy"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"Exendin-4 combined with enzalutamide significantly suppressed prostate cancer tumor growth compared to enzalutamide alone by inhibiting Akt and mTOR activation triggered by enzalutamide resistance.","whyItMatters":"Drug resistance is a major problem in prostate cancer treatment. Repurposing an existing diabetes peptide drug to overcome resistance could provide a faster path to clinical use than developing entirely new compounds.","specificNumbers":"Exendin-4 plus enzalutamide produced significantly greater tumor shrinkage than either agent alone; Akt pathway suppressed.","methodology":"In vitro experiments with LNCaP and CWR22RV1 prostate cancer cell lines plus in vivo xenograft mouse models. Measured tumor growth, invasion, migration, and key signaling pathway proteins.","limitations":"Animal study using xenograft models, which don't fully replicate human prostate cancer biology. Clinical doses and safety of exendin-4 in cancer patients haven't been established. One noted P-value (P < .5) appears to be a typo and may be less significant than intended."},{"rthcId":"RPEP-05198","title":"Advanced Age Impairs Intestinal Antimicrobial Peptide Response and Worsens Fecal Microbiome Dysbiosis Following Burn Injury in Mice.","authors":"Wheatley, Elizabeth G; Curtis, Brenda J; Hulsebus, Holly J; Boe, Devin M; Najarro, Kevin; Ir, Diana; Robertson, Charles E; Choudhry, Mashkoor A; Frank, Daniel N; Kovacs, Elizabeth J","year":2020,"journal":"Shock (Augusta, Ga.), 53(1), 71-77","doi":"10.1097/SHK.0000000000001321","pmid":"30672882","tags":["antimicrobial-peptides","gut-health","aging"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"Burn injury triggered 20-fold increases in Reg3γ, 16-fold in Reg3β, and 8-fold in CRAMP antimicrobial peptides in young mice intestines, but aged mice showed no such upregulation. Aged burned mice had the most severe microbiome dysbiosis.","whyItMatters":"Elderly patients have much higher mortality after burns, but the mechanism wasn't well understood. This study reveals that age-related failure of gut antimicrobial peptide defense is a key contributor, opening new avenues for therapeutic intervention.","specificNumbers":"Aged mice had significantly reduced antimicrobial peptide expression and greater microbiome dysbiosis post-burn.","methodology":"Murine scald burn model with aged versus young mice. Bacterial 16S-rRNA gene sequencing for microbiome profiling. Antimicrobial peptide expression measured in ileal tissue.","limitations":"Mouse model that may not perfectly replicate human physiology. Specific mouse strains and burn protocols used. Correlational relationship between AMP expression and microbiome changes doesn't prove causation."},{"rthcId":"RPEP-05199","title":"Developing a Topical Adjunct to Injectable Procedures.","authors":"Widgerow, Alan D; Jacob, Carolyn; Palm, Melanie D; Garruto, John A; Bell, Michaela","year":2020,"journal":"Journal of drugs in dermatology : JDD, 19(4), 398-404","doi":"10.36849/JDD.2020.5016","pmid":"32272517","tags":["cosmetic-peptides","general-peptide-science"],"studyType":"human","evidenceStrength":"moderate","keyFinding":"At day 2-3 post-injection, participants using the peptide-containing serum had 73% less bruise color intensity and 81% showed less bruising compared to the bland moisturizer control.","whyItMatters":"Bruising after cosmetic injections is a top patient concern that limits procedure frequency and satisfaction. A validated topical product that accelerates healing could significantly improve the injectable procedure experience.","specificNumbers":"Reduced bruising, swelling, and pain versus controls.","methodology":"Human clinical study comparing a peptide-containing topical product (INhance Post-Injection Serum with TriHex Technology) versus bland moisturizer for post-injectable procedure recovery. Bruise color intensity measured at multiple time points.","limitations":"Industry-sponsored study (Alastin Skincare). Comparison was against bland moisturizer rather than an active comparator. Specific peptide concentrations and formulation details not fully disclosed. Relatively small study window."},{"rthcId":"RPEP-05200","title":"Drug Therapy in Obesity: A Review of Current and Emerging Treatments.","authors":"Williams, David M; Nawaz, Asif; Evans, Marc","year":2020,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 11(6), 1199-1216","doi":"10.1007/s13300-020-00816-y","pmid":"32297119","tags":["glp-1-receptor-agonists","weight-management"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Emerging peptide-based obesity therapies, particularly GLP-1 analogs and unimolecular dual/triple agonists targeting GLP-1, GIP, and glucagon receptors, show encouraging preclinical and early clinical results for weight loss.","whyItMatters":"Obesity is a growing global health crisis with limited effective drug options. Understanding the full pipeline of peptide-based therapies helps contextualize the rapid advances in this field and the potential for transformative new treatments.","specificNumbers":"GLP-1 agonists produced clinically meaningful weight loss; weight regain common upon discontinuation.","methodology":"Narrative review of published literature on approved obesity pharmacotherapies and emerging drug mechanisms, including preclinical and early clinical trial data.","limitations":"Review published in 2020, before the landmark results of semaglutide and tirzepatide for obesity. Some discussed therapies may have since been discontinued or advanced significantly. Narrative review format lacks systematic methodology."},{"rthcId":"RPEP-05201","title":"Semaglutide: Charting New Horizons in GLP-1 Analogue Outcome Studies.","authors":"Williams, David M; Evans, Marc","year":2020,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 11(10), 2221-2235","doi":"10.1007/s13300-020-00917-8","pmid":"32880877","tags":["glp-1-receptor-agonists","cardiovascular-health"],"studyType":"review","evidenceStrength":"strong","keyFinding":"The SELECT trial is the first pharmacotherapy study in obesity powered for cardiovascular superiority in people without T2D, while FLOW is the first dedicated study of GLP-1 receptor analog effects on renal outcomes in diabetic kidney disease.","whyItMatters":"If semaglutide reduces cardiovascular events in obese people without diabetes and protects kidneys in diabetic kidney disease, it could transform treatment paradigms for two of the world's most common and deadly conditions.","specificNumbers":"SUSTAIN-6: 26% reduction in MACE; PIONEER 6: confirmed CV safety of oral semaglutide.","methodology":"Review of prior GLP-1 analog cardiovascular outcome trials and detailed discussion of the design and potential impact of the ongoing SELECT and FLOW semaglutide studies.","limitations":"Written before trial results were available, so conclusions are speculative. Focused on semaglutide specifically and may not generalize to all GLP-1 analogs. Long-term safety of GLP-1 agonists in non-diabetic populations was still being established."},{"rthcId":"RPEP-05202","title":"The neuropeptide substance P regulates aldosterone secretion in human adrenals.","authors":"Wils, Julien; Duparc, Céline; Cailleux, Anne-Françoise; Lopez, Antoine-Guy; Guiheneuf, Caroline; Boutelet, Isabelle; Boyer, Hadrien-Gaël; Dubessy, Christophe; Cherifi, Saloua; Cauliez, Bruno; Gobet, Françoise; Defortescu, Guillaume; Ménard, Jean-François; Louiset, Estelle; Lefebvre, Hervé","year":2020,"journal":"Nature communications, 11(1), 2673","doi":"10.1038/s41467-020-16470-8","pmid":"32471973","tags":["general-peptide-science","cardiovascular-health"],"studyType":"in_vitro","evidenceStrength":"strong","keyFinding":"Substance P stimulates aldosterone secretion through NK1 receptors via the ERK pathway. In a double-blind placebo-controlled trial, the NK1R antagonist aprepitant decreased aldosterone production by approximately 30% in healthy males.","whyItMatters":"Excess aldosterone causes hypertension and cardiovascular disease. Discovering that the nervous system directly controls aldosterone through substance P opens a completely new therapeutic pathway — and aprepitant, an already-approved drug, could potentially be repurposed for aldosterone excess syndromes.","specificNumbers":"Substance P stimulated aldosterone via NK1R/ERK pathway; overactivation found in primary aldosteronism.","methodology":"Combined in vitro mechanistic studies (adrenal cell cultures, signaling pathway analysis) with a prospective, double-blind, placebo-controlled clinical trial in healthy male volunteers testing aprepitant vs. placebo over 7-day treatment periods.","limitations":"Small proof-of-concept trial in healthy male volunteers only. Long-term effects and clinical relevance in patients with aldosterone excess syndromes need investigation. The ~30% reduction may not be sufficient as monotherapy for clinical hyperaldosteronism."},{"rthcId":"RPEP-05203","title":"Clopidogrel-Induced Gastric Injury in Rats is Attenuated by Stable Gastric Pentadecapeptide BPC 157.","authors":"Wu, Hailu; Wei, Ming; Li, Nan; Lu, Qin; Shrestha, Sachin Mulmi; Tan, Jiacheng; Zhang, Zhenyu; Wu, Guoqiu; Shi, Ruihua","year":2020,"journal":"Drug design, development and therapy, 14, 5599-5610","doi":"10.2147/DDDT.S284163","pmid":"33376304","tags":["bpc-157","gut-health"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"BPC-157 attenuated clopidogrel-induced gastric mucosa injury by inhibiting ER stress-mediated apoptosis and inflammation while promoting angiogenesis via VEGF-A/VEGFR1-mediated AKT/p38/MAPK signaling. These effects were partially dependent on nitric oxide.","whyItMatters":"Millions of people take clopidogrel for cardiovascular protection but face gastric ulcer risks. BPC-157's multi-pathway gastroprotective mechanism could offer a targeted way to protect the stomach without compromising the blood thinner's cardiovascular benefits.","specificNumbers":"BPC 157 significantly reduced gastric lesion area; L-NAME partially reversed BPC 157 protection.","methodology":"Rat model with acetic acid-induced gastric ulcers followed by clopidogrel to trigger recurrence. Groups received clopidogrel alone, with BPC-157, or with L-NAME (NO blocker). Assessed using TUNEL assay, histology, immunohistochemistry, and Western blot for CHOP, VEGF-A, VEGFR1, and eNOS.","limitations":"Animal study in rats — human dosing, safety, and efficacy are not established. The acetic acid ulcer model followed by clopidogrel may not perfectly replicate clinical ulcer recurrence in patients. BPC-157 is not yet approved for clinical use."},{"rthcId":"RPEP-05204","title":"Electrospun thymosin Beta-4 loaded PLGA/PLA nanofiber/ microfiber hybrid yarns for tendon tissue engineering application.","authors":"Wu, Shaohua; Zhou, Rong; Zhou, Fang; Streubel, Philipp N; Chen, Shaojuan; Duan, Bin","year":2020,"journal":"Materials science & engineering. C, Materials for biological applications, 106, 110268","doi":"10.1016/j.msec.2019.110268","pmid":"31753373","tags":["thymosin-beta-4","tissue-engineering"],"studyType":"in_vitro","evidenceStrength":"preliminary","keyFinding":"Thymosin beta-4 loaded PLGA/PLA hybrid yarns provided sustained drug release for 28 days and showed additive effects on promoting human adipose-derived stem cell migration, proliferation, and tenogenic differentiation compared to unloaded scaffolds.","whyItMatters":"Tendon injuries are common and difficult to treat. This approach combines a structurally biomimetic scaffold with a bioactive peptide, addressing both the mechanical and biological requirements for successful tendon regeneration.","specificNumbers":"TB4-loaded yarns enhanced cell proliferation and upregulated tendon-specific genes versus unloaded controls.","methodology":"Electrospinning fabrication of PLGA nanofiber-coated PLA microfiber yarns. Tβ4 loading and release kinetics measured. Human adipose-derived mesenchymal stem cells cultured on scaffolds with assessment of growth, proliferation, and tendon-specific gene expression.","limitations":"In vitro study only — no animal or clinical testing of the scaffold. Long-term mechanical properties under physiological loading not assessed. Optimal Tβ4 dosing for clinical tendon repair unknown."},{"rthcId":"RPEP-05205","title":"Inhibition of SARS-CoV-2 (previously 2019-nCoV) infection by a highly potent pan-coronavirus fusion inhibitor targeting its spike protein that harbors a high capacity to mediate membrane fusion.","authors":"Xia, Shuai; Liu, Mingqi; Wang, Chao; Xu, Wei; Lan, Qiaoshuai; Feng, Siliang; Qi, Feifei; Bao, Linlin; Du, Lanying; Liu, Shuwen; Qin, Chuan; Sun, Fei; Shi, Zhengli; Zhu, Yun; Jiang, Shibo; Lu, Lu","year":2020,"journal":"Cell research, 30(4), 343-355","doi":"10.1038/s41422-020-0305-x","pmid":"32231345","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05206","title":"Anti-cancer peptides: classification, mechanism of action, reconstruction and modification.","authors":"Xie, Mingfeng; Liu, Dijia; Yang, Yufeng","year":2020,"journal":"Open biology, 10(7), 200004","doi":"10.1098/rsob.200004","pmid":"32692959","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05207","title":"Splice variant of growth hormone-releasing hormone receptor drives esophageal squamous cell carcinoma conferring a therapeutic target.","authors":"Xiong, Xiao; Ke, Xiurong; Wang, Lu; Yao, Zhimeng; Guo, Yi; Zhang, Xianyang; Chen, Yuping; Pang, Chi Pui; Schally, Andrew V; Zhang, Hao","year":2020,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 117(12), 6726-6732","doi":"10.1073/pnas.1913433117","pmid":"32156725","tags":["growth-hormone-peptides","cancer-immunotherapy"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"Hypoxia-elevated SV1 splice variant activates PFKM through the NF-κB pathway, enhancing glycolytic metabolism and promoting esophageal cancer progression. GHRH-R antagonist MIA-602 reversed these malignant effects by targeting SV1.","whyItMatters":"This study explains a longstanding puzzle — why GHRH-R antagonists work against cancers that don't express the standard receptor — and identifies SV1 as the actual therapeutic target, potentially expanding the use of these drugs to more cancer types.","specificNumbers":"SV1 variant expressed in ESCC; standard pGHRH-R absent; GHRH-R antagonists significantly suppressed tumor growth.","methodology":"Esophageal squamous cell carcinoma cell models with hypoxia exposure, signaling pathway analysis (NF-κB, PFKM), metabolic profiling, and in vivo validation. MIA-602 treatment tested against SV1-driven tumor progression.","limitations":"Focused on esophageal squamous cell carcinoma; generalizability to other cancer types expressing SV1 needs validation. MIA-602 is an experimental compound not yet in clinical use."},{"rthcId":"RPEP-05208","title":"Preclinical safety evaluation of body protective compound-157, a potential drug for treating various wounds.","authors":"Xu, Chuanyang; Sun, Lijuan; Ren, FengLing; Huang, Ping; Tian, Zhuang; Cui, Jiazhen; Zhang, Wangqian; Wang, Shuning; Zhang, Kuo; He, Lei; Zhang, Wei; Zhang, Cun; Hao, Qiang; Zhang, Yingqi; Li, Meng; Li, Weina","year":2020,"journal":"Regulatory toxicology and pharmacology : RTP, 114, 104665","doi":"10.1016/j.yrtph.2020.104665","pmid":"32334036","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05209","title":"Defensins: A Double-Edged Sword in Host Immunity.","authors":"Xu, Dan; Lu, Wuyuan","year":2020,"journal":"Frontiers in immunology, 11, 764","doi":"10.3389/fimmu.2020.00764","pmid":"32457744","tags":["antimicrobial-peptides","immune-system"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Defensins exhibit paradoxical roles in immunity: while broadly antimicrobial and immunomodulatory, they can promote viral and bacterial infections in certain settings and show both tumor-proliferative and tumor-suppressive activities depending on context.","whyItMatters":"Understanding that defensins can both help and harm changes how we think about innate immune defense. This dual nature has implications for developing defensin-based therapeutics — boosting them may not always be beneficial.","specificNumbers":"Defensins active against bacteria, viruses, and fungi; pro-pathogenic roles identified in specific viral and bacterial contexts.","methodology":"Mini review of recent literature on defensin pathogenic properties in antiviral immunity, antibacterial immunity, and antitumor immunity.","limitations":"Mini review format provides breadth but limited depth on individual mechanisms. The conditions under which defensins become pathogenic are not fully defined and likely vary by tissue, pathogen, and host factors."},{"rthcId":"RPEP-05210","title":"TEX19 promotes ovarian carcinoma progression and is a potential target for epitope vaccine immunotherapy.","authors":"Xu, Zhaoxu; Tang, Haichao; Zhang, Tianshu; Sun, Mingli; Han, Qiang; Xu, Jiao; Wei, Minjie; Yu, Zhaojin","year":2020,"journal":"Life sciences, 241, 117171","doi":"10.1016/j.lfs.2019.117171","pmid":"31843525","tags":["cancer-immunotherapy"],"studyType":"in_vitro","evidenceStrength":"moderate","keyFinding":"TEX19 was significantly upregulated in ovarian cancer and correlated with higher TNM stage, lymph node involvement, and invasiveness. The TL peptide from TEX19 showed the greatest affinity with HLA-A*0201 among four candidates, making it a potential epitope vaccine target.","whyItMatters":"Ovarian cancer has high mortality and limited treatment options. Identifying TEX19 as both a cancer driver and a vaccine target offers a dual approach — understanding the biology while developing a potentially therapeutic immune response against it.","specificNumbers":"98 tissue samples analyzed; TEX19 levels correlated with prognosis; candidate epitope peptides identified.","methodology":"Immunohistochemistry in 98 human ovarian tissue samples, qRT-PCR and Western blot in cell lines, siRNA knockdown functional assays, and epitope prediction using IEDB database, pepsite2, MOE software, and T2 cell binding assay.","limitations":"Epitope prediction and T2 binding assays are preliminary steps — actual in vivo immunogenicity and anti-tumor efficacy of the TL peptide vaccine haven't been tested. HLA-A*0201 restriction limits applicability to patients with this allele type."},{"rthcId":"RPEP-05211","title":"Effect of intranasal oxytocin on the core social symptoms of autism spectrum disorder: a randomized clinical trial.","authors":"Yamasue, Hidenori; Okada, Takashi; Munesue, Toshio; Kuroda, Miho; Fujioka, Toru; Uno, Yota; Matsumoto, Kaori; Kuwabara, Hitoshi; Mori, Daisuke; Okamoto, Yuko; Yoshimura, Yuko; Kawakubo, Yuki; Arioka, Yuko; Kojima, Masaki; Yuhi, Teruko; Owada, Keiho; Yassin, Walid; Kushima, Itaru; Benner, Seico; Ogawa, Nanayo; Eriguchi, Yosuke; Kawano, Naoko; Uemura, Yukari; Yamamoto, Maeri; Kano, Yukiko; Kasai, Kiyoto; Higashida, Haruhiro; Ozaki, Norio; Kosaka, Hirotaka","year":2020,"journal":"Molecular psychiatry, 25(8), 1849-1858","doi":"10.1038/s41380-018-0097-2","pmid":"29955161","tags":["oxytocin","mental-health"],"studyType":"human","evidenceStrength":"strong","keyFinding":"No between-group difference on the primary endpoint (ADOS reciprocity, effect size -0.08, P=.69), but oxytocin significantly reduced repetitive behavior (effect size 0.44, P=.026) and increased gaze fixation on social regions (effect size 0.55, P=.018).","whyItMatters":"This is the first large-scale, rigorous trial of oxytocin for autism. While the primary endpoint was negative, the significant effects on repetitive behavior and social gaze suggest oxytocin may have specific benefits that could be optimized with different dosing, duration, or combination approaches.","specificNumbers":"106 participants; 48 IU/day intranasal oxytocin; 6-week duration; no significant difference on primary social reciprocity outcome.","methodology":"Randomized, parallel-group, multicenter, placebo-controlled, double-blind trial in Japan. 106 ASD adults (18-48 y.o.) received 6 weeks of intranasal oxytocin (48 IU/day) or placebo. Measured ADOS scores and eye-tracking gaze patterns.","limitations":"Strong placebo response on primary endpoint may have masked real effects. 6-week duration may be too short. Dose of 48 IU/day may not be optimal. Only adult males with high-functioning ASD were included, limiting generalizability."},{"rthcId":"RPEP-05212","title":"Role of the Neurokinin-1 Receptor in the Promotion of Corneal Epithelial Wound Healing by the Peptides FGLM-NH2 and SSSR in Neurotrophic Keratopathy.","authors":"Yanai, Ryoji; Nishida, Teruo; Hatano, Makoto; Uchi, Sho-Hei; Yamada, Naoyuki; Kimura, Kazuhiro","year":2020,"journal":"Investigative ophthalmology & visual science, 61(8), 29","doi":"10.1167/iovs.61.8.29","pmid":"32697304","tags":["general-peptide-science","wound-healing"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"FGLM-NH2 and SSSR promoted corneal epithelial healing through the substance P-NK-1R axis, activating Akt signaling and suppressing inflammatory cytokines IL-1α, MIP-1α, and MIP-1β. NK-1R antagonist L-733,060 abolished the healing effect.","whyItMatters":"Neurotrophic keratopathy is a sight-threatening condition with limited treatments. Understanding the specific receptor and signaling mechanism of these peptide eye drops supports their clinical development and optimization.","specificNumbers":"FGLM-NH2 promoted corneal healing; NK1R knockout or antagonism abolished the effect completely.","methodology":"Mouse model of neurotrophic keratopathy via trigeminal nerve axotomy. Corneal healing tracked by fluorescein staining and slit-lamp examination. Immunohistofluorescence for substance P, NK-1R, and phospho-Akt. Multiplex cytokine assay for inflammatory markers.","limitations":"Mouse model of neurotrophic keratopathy may not fully replicate human disease. Specific doses and treatment duration details not fully characterized. Long-term effects and optimal treatment protocols need further study."},{"rthcId":"RPEP-05213","title":"Pain May Promote Tumor Progression via Substance P-Dependent Modulation of Toll-like Receptor-4.","authors":"Yang, Chao; Sun, Yunheng; Ouyang, Xueyan; Li, Jing; Zhu, Zhen; Yu, Ruihua; Wang, Li; Jia, Lin; Ding, Gang; Wang, Yaosheng; Jiang, Feng","year":2020,"journal":"Pain medicine (Malden, Mass.), 21(12), 3443-3450","doi":"10.1093/pm/pnaa265","pmid":"32914185","tags":["general-peptide-science","cancer-immunotherapy"],"studyType":"in_vitro","evidenceStrength":"moderate","keyFinding":"Substance P was elevated in cancer patients with pain and upregulated TLR-4 expression in tumor cells via NK-1 receptors, increasing proliferation, migration, and invasion. Aprepitant blocked these effects.","whyItMatters":"This provides a molecular mechanism linking chronic pain to worse cancer outcomes — not just reduced quality of life but actual tumor progression. It suggests that NK-1R antagonists like aprepitant could serve dual roles as anti-nausea and anti-cancer agents.","specificNumbers":"Substance P elevated in advanced cancer patients; SP promoted tumor growth and suppressed immunity via TLR-4 in vitro.","methodology":"Serum samples from lung and breast cancer patients measured for substance P levels. Cell pharmacology experiments testing SP effects on TLR-4 expression, proliferation, migration, and invasion. Aprepitant (NK-1R blocker) used as a control.","limitations":"In vitro experiments may not fully replicate in vivo tumor biology. Correlation between pain, SP levels, and cancer outcomes needs prospective clinical validation. Aprepitant's clinical anti-tumor efficacy hasn't been tested in trials."},{"rthcId":"RPEP-05214","title":"Targeting the Amyloid-β Fibril Surface with a Constrained Helical Peptide Inhibitor.","authors":"Yang, Fadeng; Zhang, Wan; Jiang, Yixiang; Yin, Feng; Han, Wei; Li, Zigang","year":2020,"journal":"Biochemistry, 59(3), 290-296","doi":"10.1021/acs.biochem.9b00800","pmid":"31702899","tags":["peptide-chemistry","neurological-peptides"],"studyType":"in_vitro","evidenceStrength":"preliminary","keyFinding":"Stapled helical peptides recognized the K16-E22 region of Aβ40 fibril surfaces and inhibited surface-mediated oligomerization. The best candidate achieved ~0.75 μM binding affinity through hydrophobic staple-fibril surface interactions.","whyItMatters":"Most Alzheimer's drug approaches target soluble amyloid or prevent aggregation. Targeting the fibril surface — the actual platform that generates toxic oligomers — is a novel strategy that could complement existing approaches.","specificNumbers":"Helical peptide bound Aβ40 fibril surface K16-E22 region with micromolar affinity; blocked toxic oligomer formation.","methodology":"Peptide synthesis with in-tether chiral center-induced helical stabilization. Binding affinity measurements. Extensive computational sampling revealing two distinct binding modes. Oligomerization inhibition assays.","limitations":"In vitro study — no cellular or animal model testing. The relationship between fibril surface-mediated oligomerization and Alzheimer's pathology in vivo needs validation. Peptide drug delivery to the brain remains a major challenge."},{"rthcId":"RPEP-05215","title":"Purinergic Signaling Involvement in Thymosin β4-mediated Corneal Epithelial Cell Migration.","authors":"Yang, Heung-Mo; Kang, Shin Wook; Sung, Jihye; Kim, Kyeongsoon; Kleinman, Hynda","year":2020,"journal":"Current eye research, 45(11), 1352-1358","doi":"10.1080/02713683.2020.1748891","pmid":"32223337","tags":["thymosin-beta-4","wound-healing"],"studyType":"in_vitro","evidenceStrength":"moderate","keyFinding":"Tβ4-mediated corneal epithelial cell proliferation and migration are associated with increased extracellular ATP levels, P2X7 receptor-mediated calcium influx, and ERK1/2 phosphorylation. P2X7 antagonists blocked Tβ4-induced migration.","whyItMatters":"Understanding the signaling cascade behind Tβ4's corneal healing effects enables optimization of therapeutic formulations and identification of combination targets for enhanced corneal repair.","specificNumbers":"TB4 increased extracellular ATP; P2 receptor blockade significantly reduced TB4-mediated cell migration.","methodology":"In vitro studies on human corneal epithelial cells. Proliferation (CCK-8), gap closure migration assay, ATP measurement (ATP Lite kit), calcium imaging (Fluo 8 assay), P2X7 inhibitor studies, and Western blot for ERK1/2 phosphorylation.","limitations":"In vitro study on cultured human corneal epithelial cells — results may differ in the complex wound environment of a living eye. Specific P2X7 antagonist concentrations and their potential side effects not fully explored."},{"rthcId":"RPEP-05216","title":"Mitochondria targeted peptide SS-31 prevent on cisplatin-induced acute kidney injury via regulating mitochondrial ROS-NLRP3 pathway.","authors":"Yang, Shi-Kun; Han, Ya-Chun; He, Jin-Rong; Yang, Ming; Zhang, Wei; Zhan, Ming; Li, Ai-Mei; Li, Liu; Na-Song; Liu, Yu-Ting; Wu, Xue-Qin; Zhang, Qin; Wang, Jian-Wen; Zhang, Hao","year":2020,"journal":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 130, 110521","doi":"10.1016/j.biopha.2020.110521","pmid":"32717631","tags":["ss-31-elamipretide","kidney-health"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"SS-31 treatment suppressed mitochondrial ROS, ameliorated kidney lesions, and decreased NLRP3, IL-1β, and caspase-1 expression in both cisplatin-treated mice and HK-2 kidney cells, protecting against acute kidney injury.","whyItMatters":"Cisplatin-induced kidney injury is a major clinical problem limiting chemotherapy dosing. SS-31 (elamipretide) is already in clinical trials for other mitochondrial conditions, making this a potential near-term therapeutic option for kidney protection during chemotherapy.","specificNumbers":"32 mice; SS-31 10 mg/kg/day x 10 days; cisplatin 25 mg/kg IP; significant reduction in kidney damage, oxidative stress, and NLRP3 activation.","methodology":"In vivo: 32 C57BL/6 mice in 4 groups, cisplatin (25 mg/kg single injection), SS-31 (10 mg/kg/day for 10 days). Measured creatinine, BUN, histology, electron microscopy. In vitro: HK-2 cells with cisplatin (50 μM) ± SS-31 (100 μM). Measured mitochondrial ROS, apoptosis, NLRP3 pathway proteins.","limitations":"Single cisplatin dose model may not replicate cumulative kidney damage from repeated chemotherapy cycles. Mouse-to-human dose translation uncertain. SS-31 has not been tested for this indication in human trials."},{"rthcId":"RPEP-05217","title":"Pathophysiology and significance of natriuretic peptides in patients with end-stage kidney disease.","authors":"Yang, Wen-Ling; Fahim, Magid; Johnson, David W","year":2020,"journal":"Clinical biochemistry, 83, 1-11","doi":"10.1016/j.clinbiochem.2020.05.013","pmid":"32511964","tags":["natriuretic-peptides","cardiovascular-health","kidney-health"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Serum natriuretic peptide concentrations in ESKD patients show moderate to strong positive relationships with underlying heart disease, abnormal cardiac structure/function, and mortality, despite universally elevated baseline levels due to impaired renal clearance.","whyItMatters":"Cardiovascular disease is the leading cause of death in dialysis patients. Having reliable biomarkers to assess cardiac risk in this population could guide treatment decisions and improve outcomes — but clinicians need to know how to interpret elevated NP levels in the context of kidney failure.","specificNumbers":"NP levels universally elevated in ESKD; still prognostic for CV events and mortality.","methodology":"Narrative review of published literature on natriuretic peptide pathophysiology, clinical significance, and risk stratification utility in end-stage kidney disease patients.","limitations":"Narrative review format without systematic methodology. Inconsistent cutoff values across studies prevent definitive clinical recommendations. Limited data on some NP subtypes (CNP, DNP) in ESKD."},{"rthcId":"RPEP-05218","title":"Chitosan hydrogel encapsulated with LL-37 peptide promotes deep tissue injury healing in a mouse model.","authors":"Yang, Xu; Guo, Jing-Lin; Han, Jing; Si, Rui-Juan; Liu, Pan-Pan; Zhang, Zi-Rui; Wang, Ai-Min; Zhang, Ju","year":2020,"journal":"Military Medical Research, 7(1), 20","doi":"10.1186/s40779-020-00249-5","pmid":"32321591","tags":["ll-37-cathelicidin","wound-healing"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"LL-37/chitosan hydrogel significantly reduced pressure ulcer area to 48.12% by day 15, with increased epithelial thickness, capillary density, and upregulated HIF-1α and VEGF-A expression at both mRNA and protein levels.","whyItMatters":"Pressure ulcers affect millions of bedridden patients and are difficult to treat. A biocompatible, antibacterial, wound-healing hydrogel combining LL-37's antimicrobial and regenerative properties with sustained delivery could transform wound care.","specificNumbers":"2.5% chitosan hydrogel; no cytotoxicity; enhanced TNF-alpha; faster wound healing in mice.","methodology":"Mouse pressure ulcer model using magnets on 12/12h schedule for 21 days. Groups: LL-37/CS hydrogel (20 μg LL-37), naked LL-37 (20 μg), hydrogel alone, no treatment (n=6/group). Measured ulcer area, histology, cytotoxicity, TNF-α release, antibacterial activity, and angiogenesis markers.","limitations":"Mouse model with relatively small group sizes (n=6). Mouse skin heals differently than human skin. The magnet-based pressure ulcer model may not fully replicate clinical pressure ulcer pathophysiology. Long-term healing outcomes beyond day 21 not assessed."},{"rthcId":"RPEP-05219","title":"Thymosin alpha-1 blocks the accumulation of myeloid suppressor cells in NSCLC by inhibiting VEGF production.","authors":"Yang, Zhenzhen; Guo, Jiacheng; Cui, Kang; Du, Yabing; Zhao, Huan; Zhu, Lili; Weng, Lanling; Tang, Wenxue; Guo, Jiancheng; Zhang, Tengfei; Shi, Xiaojing; Zong, Hong; Jin, Shuiling; Ma, Wang","year":2020,"journal":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 131, 110740","doi":"10.1016/j.biopha.2020.110740","pmid":"32942159","tags":["thymosin-alpha-1","cancer-immunotherapy"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"Thymosin alpha-1 promoted M-MDSC apoptosis by reducing Bcl-2/BAX ratio and inhibited MDSC migration to tumors by suppressing HIF-1α-mediated VEGF production in tumor cells.","whyItMatters":"Thymosin alpha-1 is already approved in many countries as an immune modulator. Understanding that it works against cancer partly by blocking MDSC recruitment provides rationale for combining it with immunotherapy drugs like checkpoint inhibitors.","specificNumbers":"TA1 reduced M-MDSCs in patient blood and decreased MDSC accumulation and VEGF in mouse tumors.","methodology":"Studies on peripheral blood M-MDSCs from NSCLC patients. Mouse subcutaneous xenograft tumor model. qRT-PCR, Western blotting, flow cytometry, and immunohistochemistry to examine mechanisms.","limitations":"Xenograft models don't fully recapitulate human tumor immunology. The specific doses and timing for optimal MDSC suppression in humans need determination. Clinical trial data for Tα1 as an anti-cancer agent in NSCLC is limited."},{"rthcId":"RPEP-05220","title":"Vaccination with dendritic cells pulsed ex vivo with gp100 peptide-decorated liposomes enhances the efficacy of anti PD-1 therapy in a mouse model of melanoma.","authors":"Yazdani, Mona; Gholizadeh, Zahra; Nikpoor, Amin Reza; Hatamipour, Mahdi; Alani, Behrang; Nikzad, Hossein; Mohamadian Roshan, Nema; Verdi, Javad; Jaafari, Mahmoud Reza; Noureddini, Mahdi; Badiee, Ali","year":2020,"journal":"Vaccine, 38(35), 5665-5677","doi":"10.1016/j.vaccine.2020.06.055","pmid":"32653275","tags":["cancer-immunotherapy","drug-delivery"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"Liposomal gp100-pulsed DC vaccine combined with anti-PD-1 therapy produced the strongest anticancer immunity with significantly increased gp100-specific CD4+ and CD8+ T cell infiltration, tumor regression, prolonged survival, and enhanced IFN-γ production.","whyItMatters":"Many cancer patients don't respond to checkpoint inhibitors alone. This peptide-vaccine combination approach could convert non-responders into responders by ensuring the immune system is properly primed to recognize tumor antigens before PD-1 blockade removes the brakes.","specificNumbers":"Liposomal gp100 DC vaccine + anti-PD-1 produced strongest anticancer response versus monotherapy.","methodology":"Liposomes decorated with gp10025-33 peptide. Dendritic cells pulsed ex vivo and injected subcutaneously into mice bearing established B16F10 melanoma tumors. Combined with anti-PD-1 therapy. Assessed T cell infiltration, CTL responses, IFN-γ production, and PD-1+ TILs.","limitations":"Mouse melanoma model (B16F10) may not fully predict human responses. Single tumor antigen (gp100) targeting may be insufficient for heterogeneous human tumors. DC vaccine manufacturing is complex and costly for clinical scaling."},{"rthcId":"RPEP-05221","title":"The mitochondrial derived peptide humanin is a regulator of lifespan and healthspan.","authors":"Yen, Kelvin; Mehta, Hemal H; Kim, Su-Jeong; Lue, YanHe; Hoang, James; Guerrero, Noel; Port, Jenna; Bi, Qiuli; Navarrete, Gerardo; Brandhorst, Sebastian; Lewis, Kaitlyn Noel; Wan, Junxiang; Swerdloff, Ronald; Mattison, Julie A; Buffenstein, Rochelle; Breton, Carrie V; Wang, Christina; Longo, Valter; Atzmon, Gil; Wallace, Douglas; Barzilai, Nir; Cohen, Pinchas","year":2020,"journal":"Aging, 12(12), 11185-11199","doi":"10.18632/aging.103534","pmid":"32575074","tags":["humanin-mots-c","aging"],"studyType":"animal","evidenceStrength":"strong","keyFinding":"Humanin overexpression extended C. elegans lifespan dependent on daf-16/Foxo. HNG treatment improved metabolic healthspan and reduced inflammation in middle-aged mice. Humanin levels were elevated in children of centenarians and stable in naked mole-rats but declined with age in other species.","whyItMatters":"This is the first demonstration that a mitochondrial-derived peptide regulates lifespan and healthspan across species, from worms to humans. The correlation with exceptional human longevity makes humanin a compelling target for anti-aging research.","specificNumbers":"Humanin overexpression significantly extended worm lifespan (FOXO-dependent); transgenic mice showed improved healthspan phenotypes.","methodology":"C. elegans lifespan studies with humanin overexpression. Humanin transgenic mice phenotyping. Middle-aged mice treated twice weekly with HNG analog. Human studies measuring circulating humanin in centenarians' children, Alzheimer's patients, and MELAS patients. Naked mole-rat humanin level profiling.","limitations":"Worm and mouse lifespan studies may not directly translate to human longevity. Observational human data (centenarian children) shows correlation, not causation. Optimal dosing, timing, and safety of humanin supplementation in humans are unknown."},{"rthcId":"RPEP-05222","title":"De Novo Design of Cell-Penetrating Foldamers.","authors":"Yokoo, Hidetomo; Misawa, Takashi; Demizu, Yosuke","year":2020,"journal":"Chemical record (New York, N.Y.), 20(9), 912-921","doi":"10.1002/tcr.202000047","pmid":"32463155","tags":["peptide-chemistry","drug-delivery"],"studyType":"in_vitro","evidenceStrength":"preliminary","keyFinding":"Cell-penetrating foldamers containing various non-natural building blocks can achieve organized secondary structures that enhance cell membrane permeability, functioning as potential drug delivery system (DDS) carriers.","whyItMatters":"Natural cell-penetrating peptides face stability and specificity challenges. Foldamers — being synthetic and designable — could overcome these limitations while maintaining or exceeding the cell-penetrating ability of natural CPPs.","specificNumbers":"Multiple foldamer designs; optimal secondary structure and cationic content achieved efficient cell penetration.","methodology":"Account/mini-review describing recent advances in designing cell-penetrating foldamers with various building blocks and their applications as drug delivery carriers.","limitations":"Account/overview format with limited original data. Many foldamers discussed are at early proof-of-concept stage. In vivo performance, toxicity, and pharmacokinetics of most foldamers remain to be established."},{"rthcId":"RPEP-05223","title":"CD44-Mediated Methotrexate Delivery by Hyaluronan-Coated Nanoparticles Composed of a Branched Cell-Penetrating Peptide.","authors":"Yoo, Jisang; Rejinold, N Sanoj; Lee, DaeYong; Noh, Ilkoo; Koh, Won-Gun; Jon, Sangyong; Kim, Yeu-Chun","year":2020,"journal":"ACS biomaterials science & engineering, 6(1), 494-504","doi":"10.1021/acsbiomaterials.9b01724","pmid":"33463200","tags":["drug-delivery","cancer-immunotherapy"],"studyType":"in_vitro","evidenceStrength":"preliminary","keyFinding":"B-mR9-MTX/HA nanoparticles demonstrated glutathione-triggered degradability, CD44-mediated cancer cell targeting, efficient intracellular methotrexate delivery, and superior tumor inhibition in vivo.","whyItMatters":"Targeted drug delivery could improve cancer treatment by getting more drug to tumor cells while reducing side effects. Using cell-penetrating peptides as the delivery backbone adds the ability to enter cells efficiently, while the targeting and triggered-release features add specificity.","specificNumbers":"B-mR9/HA nanoparticles achieved selective CD44-mediated uptake and redox-triggered MTX release in cancer cells.","methodology":"Synthesis of branched modified nona-arginine (B-mR9) with redox-cleavable disulfide bonds. Methotrexate loading and hyaluronic acid coating. In vitro CD44-mediated uptake studies. In vivo tumor inhibition study.","limitations":"Early-stage in vivo data without detailed pharmacokinetics or toxicity profiles. CD44 is expressed on some normal cells, potentially causing off-target effects. Manufacturing complexity of multi-component nanoparticles may limit clinical translation."},{"rthcId":"RPEP-05224","title":"The Role of the Oxytocin System in Anxiety Disorders.","authors":"Yoon, Seoyoung; Kim, Yong-Ku","year":2020,"journal":"Advances in experimental medicine and biology, 1191, 103-120","doi":"10.1007/978-981-32-9705-0_7","pmid":"32002925","tags":["oxytocin","mental-health"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Oxytocin exerts anxiolytic effects through modulation of social cognition, fear learning/extinction, HPA axis regulation, and interactions with serotonergic and GABAergic systems, with clinical evidence supporting potential therapeutic use in social anxiety and separation anxiety disorders.","whyItMatters":"Anxiety disorders are among the most common mental health conditions, and current treatments have significant limitations. Oxytocin represents a fundamentally different therapeutic approach targeting social and emotional processing rather than just neurotransmitter levels.","specificNumbers":"Consistent anxiolytic effects in animal models; mixed but promising results in human studies for fear extinction and social anxiety.","methodology":"Chapter-format review of preclinical and clinical findings on oxytocin and anxiety disorders, covering neurobehavioral mechanisms, neuroendocrine interactions, genetic/epigenetic studies, and intranasal oxytocin trials.","limitations":"Review format with heterogeneous study designs and inconsistent findings across studies. Intranasal oxytocin delivery to the brain is debated. Individual variation in oxytocin receptor genetics may explain inconsistent clinical results."},{"rthcId":"RPEP-05225","title":"Blocking protein phosphatase 2A with a peptide protects mice against bleomycin-induced pulmonary fibrosis.","authors":"Yu, Jun; Deng, Yuanjun; Han, Min","year":2020,"journal":"Experimental lung research, 46(7), 234-242","doi":"10.1080/01902148.2020.1774823","pmid":"32584210","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05226","title":"STING controls intestinal homeostasis through promoting antimicrobial peptide expression in epithelial cells.","authors":"Yu, Yanbo; Yang, Wenjing; Bilotta, Anthony J; Yu, Yu; Zhao, Xiaojing; Zhou, Zheng; Yao, Suxia; Xu, Jimin; Zhou, Jia; Dann, Sara M; Li, Yanqing; Cong, Yingzi","year":2020,"journal":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 34(11), 15417-15430","doi":"10.1096/fj.202001524R","pmid":"32969062","tags":["antimicrobial-peptides","gut-health","immune-system"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"STING-/- mice showed increased susceptibility to C. rodentium infection with impaired bacterial clearance and lower REG3γ expression. STING agonists activated STAT3 and glycolysis in intestinal epithelial cells to promote REG3γ production, and 2,3-cGAMP treatment inhibited colitis in vivo.","whyItMatters":"Understanding how the gut maintains its antimicrobial defenses could lead to new treatments for inflammatory bowel disease and gut infections. STING agonists, already being developed for cancer immunotherapy, could be repurposed for gut health applications.","specificNumbers":"STING-/- mice: more severe inflammation, impaired bacterial clearance, reduced antimicrobial peptide expression vs WT.","methodology":"STING knockout mice infected with Citrobacter rodentium. STING agonists (CMA, DMXAA, 2,3-cGAMP) tested on intestinal epithelial cells. REG3γ-deficient cells used for pathway confirmation. STAT3 and glycolysis inhibitors used to confirm mechanism.","limitations":"Mouse model with C. rodentium — relevance to human enteric pathogens needs validation. STING agonist effects may differ in human intestinal epithelium. Long-term effects of STING activation on gut homeostasis unknown."},{"rthcId":"RPEP-05227","title":"Intraoperative single administration of neutrophil peptide 1 accelerates the early functional recovery of peripheral nerves after crush injury.","authors":"Yuan, Yu-Song; Niu, Su-Ping; Yu, Fei; Zhang, Ya-Jun; Han, Na; Lu, Hao; Yin, Xiao-Feng; Xu, Hai-Lin; Kou, Yu-Hui","year":2020,"journal":"Neural regeneration research, 15(11), 2108-2115","doi":"10.4103/1673-5374.282270","pmid":"32394969","tags":["antimicrobial-peptides","neurological-peptides"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"Single intraoperative administration of neutrophil peptide 1 (10 μg/mL) improved nerve conduction velocity, sciatic functional index, and tibialis anterior muscle fiber cross-sectional area at 4 weeks post-crush injury compared to saline controls.","whyItMatters":"Peripheral nerve injuries are common and recovery is often slow and incomplete. A single-dose peptide treatment applied during surgery is far more practical than repeated injections, making clinical translation more feasible.","specificNumbers":"Single intraoperative dose; improved nerve conduction and functional recovery in early weeks post-injury.","methodology":"Rat sciatic nerve crush injury model. Single intraoperative dose of 10 μg/mL neutrophil peptide 1 or saline. Sciatic functional index, nerve electrophysiology, histology (H&E staining), muscle wet weight, and myelinated fiber counts assessed at 4 and 8 weeks.","limitations":"Functional improvements at 4 weeks without corresponding structural changes raise questions about the durability and mechanism of benefit. No differences at 8 weeks for some measures suggest the effect may be acceleration of early recovery rather than enhanced overall regeneration. Small animal model."},{"rthcId":"RPEP-05228","title":"Pharmacological characterization of mono-, dual- and tri-peptidic agonists at GIP and GLP-1 receptors.","authors":"Yuliantie, Elita; Darbalaei, Sanaz; Dai, Antao; Zhao, Peishen; Yang, Dehua; Sexton, Patrick M; Wang, Ming-Wei; Wootten, Denise","year":2020,"journal":"Biochemical pharmacology, 177, 114001","doi":"10.1016/j.bcp.2020.114001","pmid":"32360365","tags":["glp-1-receptor-agonists","weight-management"],"studyType":"in_vitro","evidenceStrength":"moderate","keyFinding":"LY3298176 (tirzepatide) is biased toward pERK1/2 relative to cAMP at both GIPR and GLP-1R. The triple agonist showed bias toward pERK1/2 relative to β-arrestin2 recruitment at GLP-1R. Mono-agonists Pro3GIP and Lys3GIP are biased toward pERK1/2 at GIPR.","whyItMatters":"Understanding biased agonism at gut hormone receptors explains why structurally similar drugs can have different clinical effects on weight loss, blood sugar, and side effects. This knowledge could guide design of next-generation obesity and diabetes drugs.","specificNumbers":"Compared mono-, dual-, and tri-agonist profiles at GIPR, GLP-1R, and glucagon receptors.","methodology":"Pharmacological characterization using HEK293 cells recombinantly expressing human GIPR or GLP-1R. Measured cAMP accumulation, ERK1/2 phosphorylation, and β-arrestin2 recruitment to determine signaling bias compared to endogenous ligands.","limitations":"HEK293 cell overexpression system may not fully replicate signaling in native tissues. Biased agonism observed in vitro may not directly predict clinical outcomes. The relationship between ERK1/2 bias and therapeutic efficacy needs clinical validation."},{"rthcId":"RPEP-05229","title":"Lactoferrin and Its Derived Peptides: An Alternative for Combating Virulence Mechanisms Developed by Pathogens.","authors":"Zarzosa-Moreno, Daniela; Avalos-Gómez, Christian; Ramírez-Texcalco, Luisa Sofía; Torres-López, Erick; Ramírez-Mondragón, Ricardo; Hernández-Ramírez, Juan Omar; Serrano-Luna, Jesús; de la Garza, Mireya","year":2020,"journal":"Molecules (Basel, Switzerland), 25(24)","doi":"10.3390/molecules25245763","pmid":"33302377","tags":["antimicrobial-peptides","lactoferrin"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Lactoferrin and lactoferricins combat pathogens through iron sequestration, membrane disruption, biofilm inhibition, toxin neutralization, and virulence factor inhibition, with no reported pathogen resistance and demonstrated synergy with antimicrobial drugs.","whyItMatters":"With antibiotic resistance threatening modern medicine, lactoferrin represents a multi-mechanism natural antimicrobial that pathogens haven't been able to evolve resistance against — a rare and valuable property.","specificNumbers":"Multiple antimicrobial mechanisms documented: bacteriostatic, bactericidal, anti-biofilm, anti-virulence, immune-stimulating.","methodology":"Comprehensive review of published literature on lactoferrin and lactoferricin antimicrobial mechanisms against bacteria, protozoa, fungi, and viruses.","limitations":"Review focuses on in vitro and preclinical evidence — clinical trial data for lactoferrin as an antimicrobial therapy is limited. Optimal dosing, delivery methods, and clinical indications need further investigation."},{"rthcId":"RPEP-05230","title":"Personalized neoantigen-based immunotherapy for advanced collecting duct carcinoma: case report.","authors":"Zeng, Yongyi; Zhang, Wei; Li, Zhenli; Zheng, Youshi; Wang, Yingchao; Chen, Geng; Qiu, Liman; Ke, Kun; Su, Xiaoping; Cai, Zhixiong; Liu, Jingfeng; Liu, Xiaolong","year":2020,"journal":"Journal for immunotherapy of cancer, 8(1)","doi":"10.1136/jitc-2019-000217","pmid":"32439798","tags":["cancer-immunotherapy"],"studyType":"human","evidenceStrength":"preliminary","keyFinding":"After 6 cycles of neoantigen peptide vaccination and neoantigen-reactive T cell therapy, the patient achieved stable disease with significant pain relief. Post-treatment biopsy showed decreased mutant allele frequency for 92% (12/13) of targeted neoantigens.","whyItMatters":"This is the first demonstration that personalized neoantigen immunotherapy can work in collecting duct carcinoma, one of the most treatment-resistant cancers. The 92% neoantigen-targeted clone reduction is striking evidence of specific anti-tumor immunity.","specificNumbers":"1 patient; personalized neoantigen vaccine; clinical response achieved in a cancer with no standard therapy.","methodology":"Case report of a metastatic CDC patient. Tumor whole-exome sequencing identified 13 neoantigens. Long-peptide vaccine and neoantigen-reactive T cells (NRTs) prepared. Six treatment cycles administered. Monitored by imaging, pain assessment, IFN-γ ELISPOT, and tumor biopsy with allele frequency analysis.","limitations":"Single case report — cannot establish generalized efficacy. Stable disease rather than tumor regression. The relative contributions of peptide vaccination versus T-cell therapy are unclear. Long-term outcomes not reported."},{"rthcId":"RPEP-05231","title":"A polymeric nanocarrier with a tumor acidity-activatable arginine-rich (R9) peptide for enhanced drug delivery.","authors":"Zhang, Liting; Jiang, Chengtao; Zeng, Fanjun; Zhou, Haiyu; Li, Dongdong; He, Xinyu; Shen, Song; Yang, Xianzhu; Wang, Jun","year":2020,"journal":"Biomaterials science, 8(8), 2255-2263","doi":"10.1039/d0bm00069h","pmid":"32129378","tags":["drug-delivery","cancer-immunotherapy"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"Tumor acidity-activatable polyanionic coating deshielded at pH 6.5, re-exposing R9 peptide and significantly increasing intracellular drug concentration in tumor cells. The system remarkably promoted anti-tumor efficiency in tumor-bearing mice.","whyItMatters":"Tumor selectivity is the holy grail of cancer drug delivery. By exploiting the universal feature of tumor acidity to control drug release, this system could reduce off-target toxicity while increasing drug concentration at the tumor.","specificNumbers":"R9 activated at tumor pH (~6.5); inactive at normal pH (7.4); selective tumor uptake in vivo.","methodology":"Fabrication of PEG-PHEP-R9 nanoparticles coated with pH-responsive polyanionic polyphosphoester. In vitro uptake studies at pH 7.4 vs 6.5 in 4T1 cells. In vivo anti-tumor efficacy in tumor-bearing mice.","limitations":"Tested in a single tumor model (4T1). pH variations within tumors may affect consistency of activation. Manufacturing complexity of multi-layer nanoparticles could challenge clinical translation."},{"rthcId":"RPEP-05232","title":"Cholesterol-modified DP7 enhances the effect of individualized cancer immunotherapy based on neoantigens.","authors":"Zhang, Rui; Tang, Lin; Tian, Yaomei; Ji, Xiao; Hu, Qiuyue; Zhou, Bailing; Zhenyu, Ding; Heng, Xu; Yang, Li","year":2020,"journal":"Biomaterials, 241, 119852","doi":"10.1016/j.biomaterials.2020.119852","pmid":"32120313","tags":["antimicrobial-peptides","cancer-immunotherapy"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"DP7-C delivered antigens to 75-95% of DCs via caveolin/clathrin pathways and induced DC maturation via TLR2-MyD88-NF-κB. In human lung cancer patient MoDCs, antigen uptake increased from 14-40% to 88-98%, presentation from ~15% to ~65%, and mature DCs from ~20% to ~60%.","whyItMatters":"The gap between identifying cancer neoantigens and getting an effective immune response has been a major bottleneck. DP7-C's dual carrier-adjuvant function could dramatically improve personalized cancer vaccine outcomes.","specificNumbers":"DP7-C improved DC antigen uptake and tumor control vs standard delivery in mouse cancer models.","methodology":"In vitro DC uptake and maturation studies. Mouse tumor models with OVA and LL2-neoantigens. Human MoDCs from advanced lung cancer patients tested for antigen uptake, presentation, and maturation with DP7-C.","limitations":"Human data is from ex vivo MoDC stimulation, not clinical vaccine administration. Translation from mouse tumor models to human clinical response uncertain. Optimal DP7-C:antigen ratios and dosing schedules for clinical use need determination."},{"rthcId":"RPEP-05233","title":"Personalized neoantigen-pulsed dendritic cell vaccines show superior immunogenicity to neoantigen-adjuvant vaccines in mouse tumor models.","authors":"Zhang, Rui; Yuan, Fengjiao; Shu, Yang; Tian, Yaomei; Zhou, Bailing; Yi, Linglu; Zhang, Xueyan; Ding, Zhenyu; Xu, Heng; Yang, Li","year":2020,"journal":"Cancer immunology, immunotherapy : CII, 69(1), 135-145","doi":"10.1007/s00262-019-02448-z","pmid":"31807878","tags":["cancer-immunotherapy"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"Neoantigen-pulsed DC vaccines induced T-cell immune responses for 6/6 neoantigens vs. 4/6 for adjuvant vaccines, and anti-tumor effects for 5/6 vs. 2/6 neoantigens in LL2 lung carcinoma models.","whyItMatters":"As personalized cancer vaccines move toward clinical use, choosing the right delivery platform matters enormously. This head-to-head comparison provides evidence that DC-based delivery may produce more reliable immune and anti-tumor responses.","specificNumbers":"DC-pulsed vaccines showed superior T cell responses and tumor control vs adjuvant vaccines with same neoantigens.","methodology":"Murine lung carcinoma (LL2) candidate neoantigens used in both DC-pulsed and adjuvant vaccine formats. IFN-γ ELISPOT for immune responses. Tumor growth assessment for anti-tumor effects. Direct head-to-head comparison.","limitations":"Mouse lung carcinoma model may not predict human responses. Only 6 neoantigens tested from one tumor model. DC vaccine manufacturing is more complex and expensive than adjuvant vaccines, which may affect clinical feasibility."},{"rthcId":"RPEP-05234","title":"Functional interaction between Ghrelin and GLP-1 regulates feeding through the vagal afferent system.","authors":"Zhang, Weidong; Waise, T M Zaved; Toshinai, Koji; Tsuchimochi, Wakaba; Naznin, Farhana; Islam, Md Nurul; Tanida, Ryota; Sakoda, Hideyuki; Nakazato, Masamitsu","year":2020,"journal":"Scientific reports, 10(1), 18415","doi":"10.1038/s41598-020-75621-5","pmid":"33116243","tags":["glp-1-receptor-agonists","growth-hormone-peptides","weight-management"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"GLP-1 and ghrelin receptors co-localize on vagal afferent neurons innervating the stomach. Each peptide abolishes the electrical and feeding effects of the subsequently administered peptide. Ghrelin generates hyperpolarizing current while GLP-1 generates depolarizing current in isolated nodose ganglia neurons.","whyItMatters":"Understanding how hunger and satiety signals interact at the neural level is fundamental to developing better obesity and appetite disorder treatments. This mutual antagonism through shared neurons reveals a key regulatory checkpoint.","specificNumbers":"30-min pre-administration of either peptide abolished the other's feeding effect; vagal afferent pathway confirmed.","methodology":"In vivo feeding studies in rats and mice with sequential peptide administration. Fos expression in nodose ganglia. Electrophysiology of vagal afferents. Calcium imaging in isolated nodose ganglia neurons. Patch-clamp experiments measuring ghrelin and GLP-1 currents.","limitations":"Animal study — human vagal neuron signaling may differ. The timing dependency (first peptide 'wins') observed in acute experiments may not fully apply to chronic drug administration. In vivo confirmation of electrophysiological findings is indirect."},{"rthcId":"RPEP-05235","title":"Preparation of a new combination nanoemulsion-encapsulated MAGE1-MAGE3-MAGEn/HSP70 vaccine and study of its immunotherapeutic effect.","authors":"Zhang, Xiumin; Huang, Yang; Li, Xia; Wang, Yanxia; Yuan, Yuan; Li, Mingyang","year":2020,"journal":"Pathology, research and practice, 216(6), 152954","doi":"10.1016/j.prp.2020.152954","pmid":"32321658","tags":["cancer-immunotherapy"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"Nanoemulsion-encapsulated MAGE multi-antigen/HSP70 vaccine elicited significantly stronger cellular immune responses (IFN-γ ELISPOT and cytotoxicity) and anti-tumor effects than non-encapsulated vaccine in humanized SCID mice bearing hepatic cancer.","whyItMatters":"Single-antigen cancer vaccines often fail because tumors are heterogeneous. This multi-antigen approach combined with nanoparticle delivery addresses both antigen coverage and immune activation efficiency.","specificNumbers":"Triple MAGE/HSP70 nanoemulsion vaccine inhibited tumor growth and enhanced immune responses in humanized mice.","methodology":"Nanoemulsion prepared by magnetic ultrasonic technique. Humanized SCID mice (human PBMCs injected) challenged with M3-HHCC hepatic cancer cells. Immunized with NE(M1M3MnH) or M1M3MnH. IFN-γ ELISPOT, cytotoxicity assays, and tumor challenge experiments.","limitations":"Humanized SCID mouse model has limitations in recapitulating full human immune responses. MAGE antigens are shared tumor antigens (not personalized neoantigens). Long-term efficacy and safety not assessed."},{"rthcId":"RPEP-05236","title":"Activation of the RAS/B-RAF-MEK-ERK pathway in satellite glial cells contributes to substance p-mediated orofacial pain.","authors":"Zhang, Yan-Yan; Song, Ning; Liu, Fei; Lin, Jiu; Liu, Meng-Ke; Huang, Chao-Lan; Liao, Da-Qing; Zhou, Cheng; Wang, Hang; Shen, Jie-Fei","year":2020,"journal":"The European journal of neuroscience, 51(11), 2205-2218","doi":"10.1111/ejn.14619","pmid":"31705725","tags":["general-peptide-science","pain-management"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"Substance P upregulated NK-1 receptor expression in trigeminal satellite glial cells via the PKA/RAS-B-RAF-MEK-ERK pathway. NK-1R antagonist, MEK inhibitor, RAF inhibitor, and PKA inhibitor all reduced NK-1 expression and pain behavior, while PKC inhibitor did not.","whyItMatters":"Understanding the molecular feedback loop that amplifies chronic facial pain could lead to more targeted treatments. Multiple points in this pathway (NK-1R, RAF, MEK, PKA) represent potential drug targets for conditions like trigeminal neuralgia and TMJ disorders.","specificNumbers":"SP activated ERK1/2, PKA, PKC via NK1R; RAS/B-RAF-MEK-ERK pathway identified as key mediator of glial-mediated pain.","methodology":"In vivo CFA-induced inflammatory orofacial pain model in rats. In vitro SGC cultures treated with substance P and pathway inhibitors. Pre-injection of inhibitors into trigeminal ganglion. qPCR, Western blot, and behavioral pain assessment.","limitations":"Rat model of orofacial pain may not perfectly replicate human trigeminal pain conditions. In vitro SGC cultures may behave differently than in vivo. Some inhibitors used (e.g., sorafenib) have broad activity and clinical side effects."},{"rthcId":"RPEP-05237","title":"The effects and mechanism of collagen peptide and elastin peptide on skin aging induced by D-galactose combined with ultraviolet radiation.","authors":"Zhang, Zejun; Zhu, Huawei; Zheng, Yating; Zhang, Lanyue; Wang, Xiaoling; Luo, Zhen; Tang, Jian; Lin, Li; Du, Zhiyun; Dong, Changzhi","year":2020,"journal":"Journal of photochemistry and photobiology. B, Biology, 210, 111964","doi":"10.1016/j.jphotobiol.2020.111964","pmid":"32717457","tags":["collagen-peptides","skin-aging","cosmetic-peptides"],"studyType":"Preclinical (Animal Study)","evidenceStrength":"Preliminary","keyFinding":"Oral administration of collagen peptide (CP) and elastin peptide (EP) together reversed skin aging in mice subjected to both D-galactose (which accelerates aging) and UV radiation. The combination increased collagen and elastin content in the skin, boosted hyaluronic acid and hydroxyproline levels, and reduced MMP-3 (a collagen-destroying enzyme) and IL-1α (an inflammatory marker).\n\nThe molecular mechanism involved upregulation of seven key factors involved in collagen and elastin synthesis: IGF-1, LOX, SMAD2, JNK, SP1, TβRII, and TGF-β. Importantly, the collagen and elastin peptides appeared to work synergistically — together they were more effective than either alone.","whyItMatters":"This study provides mechanistic evidence for oral collagen and elastin supplementation — showing they don't just passively provide building materials but actively signal skin cells to increase collagen/elastin production and reduce the enzymes that break them down. The synergistic effect between the two peptide types suggests that combination supplements may be more effective than collagen alone, which is how most products are currently formulated.","specificNumbers":"Oral CP + EP · increased skin collagen + elastin content · increased hyaluronic acid + hydroxyproline · decreased MMP-3 + IL-1α · upregulated IGF-1, LOX, SMAD2, JNK, SP1, TβRII, TGF-β · synergistic effects","methodology":"Mice were treated with D-galactose injection (to accelerate systemic aging) and UV radiation (to induce photoaging), creating a dual aging model. Groups received oral collagen peptide, elastin peptide, or the combination. Skin was analyzed for collagen/elastin content, hyaluronic acid, hydroxyproline, MMP-3, IL-1α levels, and the expression of seven collagen/elastin synthesis-related signaling factors.","limitations":"Mouse skin differs significantly from human skin in thickness, structure, and UV response. The D-galactose aging model is artificial and may not fully replicate natural human aging. Specific peptide doses and molecular weights are not provided in the abstract. The study does not include human subjects or measure clinical skin parameters (wrinkle depth, elasticity, hydration). The source and preparation of the collagen and elastin peptides are not detailed."},{"rthcId":"RPEP-05238","title":"GIP has neuroprotective effects in Alzheimer and Parkinson's disease models.","authors":"Zhang, Zhen Qiang; Hölscher, Christian","year":2020,"journal":"Peptides, 125, 170184","doi":"10.1016/j.peptides.2019.170184","pmid":"31705913","tags":["glp-1-receptor-agonists","neurological-peptides"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"GIP shows neuroprotective effects in both Alzheimer's and Parkinson's disease models by restoring energy utilization, reducing inflammation, protecting synapses, and reducing pathological proteins. Dual GLP-1/GIP receptor agonists with enhanced BBB penetration show improved neuroprotection.","whyItMatters":"With no effective disease-modifying treatments for Alzheimer's or Parkinson's, repurposing gut hormone analogs represents a promising new approach. The success of GLP-1 drugs in early clinical trials for these conditions, combined with GIP's additional neuroprotective properties, suggests dual agonists could be even more effective.","specificNumbers":"GIP improved brain energy use and reduced pro-inflammatory cytokines in both AD and PD models.","methodology":"Review of preclinical studies testing GIP and GIP receptor agonists in animal models of Alzheimer's and Parkinson's disease. Discussion of dual GLP-1/GIP agonists with cell-penetrating sequences for improved blood-brain barrier crossing.","limitations":"Primarily preclinical evidence from animal models. Clinical trial data for GIP-specific neuroprotection is limited. Blood-brain barrier penetration remains a key challenge for peptide drugs. Long-term safety of dual agonists in the brain is unknown."},{"rthcId":"RPEP-05239","title":"Controlled release of basic fibroblast growth factor from a peptide biomaterial for bone regeneration.","authors":"Zhao, WeiKang; Li, Yuling; Zhou, Ao; Chen, Xiaojun; Li, Kai; Chen, Sinan; Qiao, Bo; Jiang, Dianming","year":2020,"journal":"Royal Society open science, 7(4), 191830","doi":"10.1098/rsos.191830","pmid":"32431879","tags":["tissue-engineering","peptide-chemistry"],"studyType":"in_vitro","evidenceStrength":"preliminary","keyFinding":"nHA/PA66/D-RADA16/bFGF reduced hydrogel degradation rate and prolonged bFGF sustained release, promoting BMSC proliferation, adhesion, and osteogenesis in vitro and bone repair in vivo.","whyItMatters":"Self-assembling peptide scaffolds represent an elegant solution for bone tissue engineering — they create a biomimetic matrix that can be loaded with growth factors for sustained delivery, potentially improving outcomes for patients with large bone defects.","specificNumbers":"D-RADA16 gel on nHA/PA66: controlled bFGF release; enhanced BMSC proliferation and ALP activity.","methodology":"D-RADA16 peptide hydrogel coated on nHA/PA66 artificial bone. TEM and SEM characterization. BMSC proliferation (CCK-8), adhesion (confocal microscopy), osteogenic differentiation (Alizarin Red S, alkaline phosphatase staining). In vivo bone repair evaluation.","limitations":"Specific in vivo bone defect model and timeline not detailed in abstract. Long-term mechanical properties under physiological loading not fully characterized. Clinical-grade manufacturing of peptide hydrogel-coated implants needs development."},{"rthcId":"RPEP-05240","title":"Nesiritide in patients with acute myocardial infarction and heart failure: a meta-analysis.","authors":"Zhao, Xuecheng; Zhang, Da-Qi; Song, Rongjing; Zhang, Guoqiang","year":2020,"journal":"The Journal of international medical research, 48(1), 300060519897194","doi":"10.1177/0300060519897194","pmid":"31948318","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05241","title":"Development of Conformationally Constrained α-RgIA Analogues as Stable Peptide Antagonists of Human α9α10 Nicotinic Acetylcholine Receptors.","authors":"Zheng, Nan; Christensen, Sean B; Blakely, Alan; Dowell, Cheryl; Purushottam, Landa; McIntosh, J Michael; Chou, Danny Hung-Chieh","year":2020,"journal":"Journal of medicinal chemistry, 63(15), 8380-8387","doi":"10.1021/acs.jmedchem.0c00613","pmid":"32597184","tags":["venom-derived-peptides","pain-management"],"studyType":"in_vitro","evidenceStrength":"moderate","keyFinding":"Lactam-bridged α-RgIA analogues maintained high potency and selectivity for human α9α10 nAChR with enhanced serum stability. NMR confirmed the macrocyclic peptide preserves the native conformation. Molecular docking rationalized selective binding.","whyItMatters":"Non-opioid pain treatments are urgently needed. This work transforms a fragile natural venom peptide into a stable drug candidate by solving its key pharmaceutical weakness — instability — while maintaining its desirable pharmacological properties.","specificNumbers":"Constrained analogs: high potency, receptor selectivity, enhanced human serum stability vs natural alpha-RgIA.","methodology":"Peptide synthesis with lactam bridge introduction. Electrophysiology for receptor potency and selectivity. NMR structure determination. Serum stability assays. Molecular docking modeling for binding rationalization.","limitations":"In vitro receptor and stability studies — no in vivo pain model testing reported. Route of administration for clinical use uncertain (venom peptides often require intrathecal delivery). Manufacturing costs of constrained peptides may be prohibitive."},{"rthcId":"RPEP-05242","title":"(EX-4)2-Fc, an effective long-acting GLP-1 receptor agonist, reduces obesity-related inflammation by inhibiting leptin expression.","authors":"Zhou, Bailing; Dong, Chunyan; Zhao, Binyan; Su, Xiaoqing; Luo, Yi; Xie, Li; Tian, Yaomei; Zhang, Rui; Yang, Li","year":2020,"journal":"Biochemical and biophysical research communications, 529(3), 562-568","doi":"10.1016/j.bbrc.2020.06.054","pmid":"32736674","tags":["glp-1-receptor-agonists","inflammation","weight-management"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"(EX-4)2-Fc significantly reduced proinflammatory cytokines, macrophage numbers, and shifted M1 to M2 macrophage polarization in adipose tissue of DIO mice. The anti-inflammatory effect was mediated by leptin suppression and MAPK/NF-κB pathway modulation.","whyItMatters":"GLP-1 drugs' anti-inflammatory effects may be as important as their metabolic benefits. Understanding that they work partly through leptin suppression and macrophage reprogramming could lead to optimized treatments that address both obesity and its inflammatory consequences.","specificNumbers":"(EX-4)2-Fc reduced weight, improved glucose tolerance, lowered leptin, suppressed M1 macrophages independently of weight loss.","methodology":"Diet-induced obesity (DIO) mouse model treated with (EX-4)2-Fc. Measured proinflammatory cytokines, macrophage polarization markers, MAPK and NF-κB pathway components, and leptin expression in adipose tissue.","limitations":"Mouse model — human adipose tissue inflammation dynamics may differ. (EX-4)2-Fc is a novel construct not yet in clinical use. The causal relationship between leptin reduction and anti-inflammatory effects needs further confirmation."},{"rthcId":"RPEP-05243","title":"Molecular modeling and rational design of hydrocarbon-stapled/halogenated helical peptides targeting CETP self-binding site: Therapeutic implication for atherosclerosis.","authors":"Zhu, Jian; Wei, Sen; Huang, Linchen; Zhao, Qi; Zhu, Haichao; Zhang, Anwei","year":2020,"journal":"Journal of molecular graphics & modelling, 94, 107455","doi":"10.1016/j.jmgm.2019.107455","pmid":"31586754","tags":["peptide-chemistry","cardiovascular-health"],"studyType":"in_vitro","evidenceStrength":"preliminary","keyFinding":"Stapled/halogenated helical peptides achieved >5-fold improved binding affinity for the CETP self-binding site compared to native peptide. Stapling reduced conformational disorder in free state without perturbing binding mode, enhancing competitive potency.","whyItMatters":"CETP inhibitors have been a long-sought target for treating atherosclerosis. This peptide-based approach offers a new strategy targeting CETP's self-binding mechanism rather than its active site, potentially achieving different and complementary effects to existing small-molecule inhibitors.","specificNumbers":"Designed stapled/halogenated peptides showed favorable binding to CETP self-binding site in simulations.","methodology":"Molecular dynamics simulation for peptide design. Hydrocarbon-stapling optimization based on helical pattern and binding mode. Circular dichroism for helicity measurement. Fluorescence assay for binding affinity. Computational structural examination.","limitations":"Computational and in vitro study — no cellular or animal model testing. The therapeutic window between CETP inhibition benefit and potential adverse effects needs evaluation. Clinical delivery of stapled peptides for cardiovascular disease presents challenges."},{"rthcId":"RPEP-05244","title":"Cathelicidin represents a new target for manipulation of skin inflammation in Netherton syndrome.","authors":"Zingkou, Eleni; Pampalakis, Georgios; Sotiropoulou, Georgia","year":2020,"journal":"Biochimica et biophysica acta. Molecular basis of disease, 1866(10), 165831","doi":"10.1016/j.bbadis.2020.165831","pmid":"32442469","tags":["ll-37-cathelicidin","inflammation"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"Camp deletion in Spink5-/- mice suppressed epidermal inflammation and restored abnormal differentiation. Joint Klk5 and Camp invalidation significantly extended survival. Cathelicidin is causally implicated in NS-associated skin inflammation.","whyItMatters":"Netherton syndrome has no effective targeted therapy. Identifying cathelicidin as a driver of its skin inflammation opens the door to repurposing existing drugs that reduce cathelicidin expression — a faster path to treatment than developing new compounds.","specificNumbers":"70% mortality in double-KO mice; cathelicidin deletion significantly reduced skin inflammation.","methodology":"Genetic knockout studies in Netherton syndrome mouse model (Spink5-/-). Triple knockout (Spink5-/-Klk5-/-Camp-/-) survival analysis. Epidermal inflammation and differentiation assessed histologically.","limitations":"Mouse model — genetic deletion is more complete than any pharmacological intervention. Cathelicidin reduction alone didn't rescue the barrier defect or lethality. Drug candidates that reduce cathelicidin need clinical testing for NS."},{"rthcId":"RPEP-05245","title":"Antihypertensive and antioxidant activities of enzymatic wheat bran protein hydrolysates.","authors":"Zou, Zhipeng; Wang, Mingjie; Wang, Zhigao; Aluko, Rotimi E; He, Rong","year":2020,"journal":"Journal of food biochemistry, 44(1), e13090","doi":"10.1111/jfbc.13090","pmid":"31663146","tags":["bioactive-peptides"],"studyType":"animal","evidenceStrength":"preliminary","keyFinding":"Peptides derived from wheat bran protein demonstrated significant blood pressure-lowering and antioxidant effects. When wheat bran protein was enzymatically digested and separated by size, the smallest fraction (under 1 kDa) showed the strongest activity — reducing systolic blood pressure by 35 mmHg in spontaneously hypertensive rats after a single oral dose, compared to 20 mmHg for the unfractionated hydrolysate.\n\nThe small peptide fraction also showed superior ACE-inhibitory and renin-inhibitory activity in lab tests. Seven specific peptides were identified (NL, QL, FL, HAL, AAVL, AKTVF, and TPLTR), suggesting these short peptide sequences are responsible for the blood pressure-lowering effect.","whyItMatters":"High blood pressure affects over a billion people worldwide. Finding natural, food-derived peptides that can lower blood pressure offers the possibility of functional foods or nutraceuticals with fewer side effects than pharmaceutical drugs. Wheat bran is an abundant agricultural byproduct, making these peptides potentially scalable and affordable.","specificNumbers":"<1 kDa fraction: -35 mmHg SBP reduction · WPH: -20 mmHg SBP reduction · Dose: 100 mg/kg oral · 7 peptides identified · 6 hr measurement period","methodology":"Researchers extracted protein from wheat bran and digested it with the enzyme alcalase to produce a protein hydrolysate. This was then separated through ultrafiltration membranes into fractions of different molecular sizes (above and below 1 kDa). Each fraction was tested for ACE inhibition, renin inhibition, and antioxidant capacity in the lab. The most promising fraction was then given orally to spontaneously hypertensive rats at 100 mg/kg body weight, and blood pressure was monitored for 6 hours. Individual peptides were identified using mass spectrometry.","limitations":"This was an animal study using spontaneously hypertensive rats — blood pressure effects may not translate directly to humans. Only a single oral dose was tested, so long-term effects and safety are unknown. The bioavailability and stability of these peptides in the human digestive system was not confirmed."},{"rthcId":"RPEP-05246","title":"Modulation of Orai1 by cationic peptides triggers their direct cytosolic uptake.","authors":"Zuconelli, Cristiane R; Schmidt, Samuel; Wallbrecher, Rike; van Oostrum, Jenny; Bartels, Yvonne L; Didan, Yuliia; Berendsen, Mike L T; Brock, Roland; Adjobo-Hermans, Merel J W","year":2020,"journal":"Biochimica et biophysica acta. Biomembranes, 1862(3), 183155","doi":"10.1016/j.bbamem.2019.183155","pmid":"31846645","tags":["peptide-chemistry","drug-delivery"],"studyType":"in_vitro","evidenceStrength":"moderate","keyFinding":"Rapid cytosolic CPP import depends on calcium influx via Orai1. Cell surface sialic acids mediate peptide-Orai1 interaction. Blocking Orai1 or sialic acids inhibited uptake; thapsigargin (Orai1 activator) reconstituted uptake at low peptide concentrations.","whyItMatters":"Understanding exactly how CPPs enter cells is crucial for optimizing peptide drug delivery. This Orai1-calcium mechanism provides specific molecular targets for enhancing or controlling peptide uptake into cells.","specificNumbers":"CPPs >10 μM activated Orai1; calcium influx triggered ASMase; resulted in rapid cytosolic import.","methodology":"In vitro studies with arginine-rich CPPs at various concentrations. Calcium channel modulators (thapsigargin, Orai1 blockers). Sialylation inhibition and chemical sialic acid blocking. Fluorescent peptide uptake quantification.","limitations":"In vitro cell culture system — in vivo CPP uptake may involve additional mechanisms. The 10 μM threshold may not be achievable for all therapeutic applications. Cell type-specific Orai1 expression could affect generalizability."},{"rthcId":"RPEP-05247","title":"Elamipretide Attenuates Pyroptosis and Perioperative Neurocognitive Disorders in Aged Mice.","authors":"Zuo, Youmei; Yin, Lei; Cheng, Xinqi; Li, Jun; Wu, Hao; Liu, Xuesheng; Gu, Erwei; Wu, Jing","year":2020,"journal":"Frontiers in cellular neuroscience, 14, 251","doi":"10.3389/fncel.2020.00251","pmid":"32903868","tags":["ss-31-elamipretide","neurological-peptides"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"Elamipretide protected against surgery-induced mitochondrial dysfunction, NLRP3 inflammasome-caspase-1 pyroptosis activation, synaptic protein downregulation, and cognitive deficits in aged mice hippocampus.","whyItMatters":"Post-operative cognitive decline is a major concern for elderly surgical patients, with limited preventive strategies. Elamipretide's ability to protect brain mitochondria and prevent inflammatory cell death could offer a pre-operative neuroprotective strategy.","specificNumbers":"SS-31 reduced pyroptosis markers, inflammatory cytokines, and preserved cognitive function in aged surgical mice.","methodology":"PND model via exploratory laparotomy under isoflurane in aged mice. Assessed cognitive function (behavioral tests), synaptic integrity proteins, neuroinflammation markers, mitochondrial function/morphology, and NLRP3-caspase-1 pyroptosis pathway.","limitations":"Mouse model with a single surgical intervention. Translation to human PND requires clinical trials. Optimal dosing, timing (pre-operative vs. peri-operative), and duration for human neuroprotection need determination."},{"rthcId":"RPEP-05248","title":"Sah 2021 Npy Ptsd Translational Update","authors":"","year":2021,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05249","title":"Sikiric 2021 Bpc157 Review Mechanisms","authors":"","year":2021,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05250","title":"Wang 2021 Ll37 Sars Cov2 Antiviral","authors":"","year":2021,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05251","title":"The potential role of incretin-based therapies for polycystic ovary syndrome: a narrative review of the current evidence.","authors":"Abdalla, Mohammed Altigani; Deshmukh, Harshal; Atkin, Stephen; Sathyapalan, Thozhukat","year":2021,"journal":"Therapeutic advances in endocrinology and metabolism, 12, 2042018821989238","doi":"10.1177/2042018821989238","pmid":"33552465","tags":["glp-1-receptor-agonists","hormonal-health"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"GLP-1 RAs and DPP-4 inhibitors showed significant improvements in metabolic parameters (weight, insulin sensitivity), hormonal parameters (reduced androgens, increased SHBG), and reproductive outcomes (improved menstrual regularity, ovulation, and pregnancy) in PCOS.","whyItMatters":"PCOS has limited treatment options and current therapies often address only individual symptoms. GLP-1 drugs could simultaneously improve metabolic, hormonal, and reproductive outcomes — a comprehensive approach to this multi-faceted condition.","specificNumbers":"GLP-1 agonists improved IR and weight in PCOS; some evidence for reproductive benefits.","methodology":"Narrative review with systematic search of PubMed, MEDLINE, and EMBASE. Identified 854 articles; included 8 animal intervention studies, 14 human intervention studies, 2 case-control studies, 1 observational animal study, and 1 systematic review.","limitations":"Narrative review format. Most included studies were small. Heterogeneous study designs and PCOS definitions. Larger randomized controlled trials are needed. Long-term safety of GLP-1 drugs in reproductive-age women needs evaluation."},{"rthcId":"RPEP-05252","title":"D-Amino Acids and D-Amino Acid-Containing Peptides: Potential Disease Biomarkers and Therapeutic Targets?","authors":"Abdulbagi, Mohamed; Wang, Liya; Siddig, Orwa; Di, Bin; Li, Bo","year":2021,"journal":"Biomolecules, 11(11)","doi":"10.3390/biom11111716","pmid":"34827714","tags":[],"studyType":"review","evidenceStrength":"n/a","keyFinding":"D-amino acids and D-amino acid-containing peptides (DAACPs) have been found in patients with cataracts, Alzheimer's disease, and other conditions, where they may serve as disease biomarkers or therapeutic targets. The spontaneous conversion of L-amino acids to their D-form in long-lived proteins alters protein structure and function, potentially contributing to disease progression. Elevated free D-amino acid levels in certain diseases reflect altered metabolism and may provide diagnostic value. Advances in analytical techniques are improving our ability to detect and study these mirror-image molecules.","whyItMatters":"Most biology assumes all amino acids are L-form, but D-amino acids accumulate naturally in aging tissues and diseased proteins. This review highlights an underappreciated dimension of peptide biochemistry: the spontaneous flip from L to D in proteins like beta-amyloid (Alzheimer's) and lens crystallins (cataracts) may actively drive disease rather than being a passive consequence. Understanding this process could reveal new diagnostic biomarkers and drug targets.","specificNumbers":"DAACPs found in: cataracts, Alzheimer's disease, and other conditions · Free D-amino acids: altered levels in multiple diseases · Focus: L→D conversion in long-lived proteins","methodology":"Literature review summarizing the occurrence of D-amino acids and DAACPs in disease, their molecular mechanisms of formation, links to disease development, and recent advances in analytical detection techniques.","limitations":"Narrative review without systematic methodology. The field of D-amino acid biology in disease is still developing, with many findings correlational rather than causal. Analytical challenges in detecting D-amino acids have historically limited research in this area."},{"rthcId":"RPEP-05253","title":"Measuring the oral bioavailability of protein hydrolysates derived from food sources: A critical review of current bioassays.","authors":"Abeer, Muhammad Mustafa; Trajkovic, Sanja; Brayden, David J","year":2021,"journal":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 144, 112275","doi":"10.1016/j.biopha.2021.112275","pmid":"34628165","tags":["collagen-peptides","general-peptide-science"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Current in vitro permeability assays have limitations in predicting oral bioavailability of food-derived bioactive peptides. Advanced mass spectrometry and peptidomics are needed to detect individual peptides from complex hydrolysates in biological samples.","whyItMatters":"The bioactive peptide supplement industry is growing rapidly, but much of the evidence relies on in vitro studies. Without better bioavailability measurements, it's difficult to know which food-derived peptides actually deliver health benefits when consumed orally.","specificNumbers":"In vitro assays poorly predict absorption; blood levels of food peptides very low in animal and human studies.","methodology":"Critical review of in vitro digestion assays, permeation models, and metabolism studies as predictors of oral bioavailability. Discussion of analytical challenges and potential improvements.","limitations":"Review identifies problems but doesn't provide definitive solutions. The relationship between detectable blood levels and biological activity remains poorly defined. Standardization of bioavailability methods is lacking."},{"rthcId":"RPEP-05254","title":"Endogenous Opioid Peptides and Alternatively Spliced Mu Opioid Receptor Seven Transmembrane Carboxyl-Terminal Variants.","authors":"Abrimian, Anna; Kraft, Tamar; Pan, Ying-Xian","year":2021,"journal":"International journal of molecular sciences, 22(7)","doi":"10.3390/ijms22073779","pmid":"33917474","tags":["general-peptide-science","pain-management"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Endogenous opioid peptides show variant-specific pharmacological profiles across OPRM1 7TM C-terminal splice variants, with distinct patterns of receptor binding, G protein activation, and β-arrestin2 recruitment indicating biased signaling.","whyItMatters":"Understanding how natural opioid peptides signal differently through receptor variants could reveal why some pathways produce pain relief without addiction, potentially guiding the development of safer opioid alternatives.","specificNumbers":"Three endogenous opioid families; extensive OPRM1 splice variants; differential interactions affecting pain, reward, emotion.","methodology":"Review of pharmacological studies examining endogenous opioid peptide interactions with mouse, rat, and human OPRM1 7TM C-terminal variants. Covers binding affinity, G protein activation, β-arrestin2 recruitment, and biased signaling.","limitations":"Review of primarily in vitro pharmacological data. Translation of receptor-level signaling differences to in vivo analgesic and addictive effects is complex. Species differences between mouse, rat, and human variants add complexity."},{"rthcId":"RPEP-05255","title":"Neurokinin-1 Receptor (NK-1R) Antagonists: Potential Targets in the Treatment of Glioblastoma Multiforme.","authors":"Afshari, Amir R; Motamed-Sanaye, Ali; Sabri, Hamed; Soltani, Arash; Karkon-Shayan, Sepideh; Radvar, Sarvin; Javid, Hossein; Mollazadeh, Hamid; Sathyapalan, Thozhukat; Sahebkar, Amirhossein","year":2021,"journal":"Current medicinal chemistry, 28(24), 4877-4892","doi":"10.2174/0929867328666210113165805","pmid":"33441062","tags":["general-peptide-science","cancer-immunotherapy"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"SP/NK-1R signaling controls GBM cell growth, exerts anti-apoptotic effects, stimulates invasion/metastasis, and activates vascularization. NK-1R antagonists can block these cancer-promoting effects and represent a potential additional treatment target.","whyItMatters":"GBM survival remains dismal despite decades of research. Repurposing NK-1R antagonists (already FDA-approved for other uses) could provide an accessible new treatment option, either alone or in combination with standard therapies.","specificNumbers":"GBM survival <1 year; NK-1R antagonists inhibited growth, invasion, and apoptosis resistance in preclinical GBM studies.","methodology":"Review of published literature on substance P/NK-1R pathway roles in glioblastoma and other cancers, with evaluation of NK-1R antagonist therapeutic potential.","limitations":"Review-level evidence — clinical trials of NK-1R antagonists in GBM have not been conducted. Blood-brain barrier penetration of NK-1R antagonists varies. The relative contribution of SP/NK-1R signaling versus other oncogenic pathways in GBM is unclear."},{"rthcId":"RPEP-05256","title":"Usefulness of cell-penetrating peptides and penetration accelerating sequence for nose-to-brain delivery of glucagon-like peptide-2.","authors":"Akita, Tomomi; Kimura, Ryosuke; Akaguma, Saki; Nagai, Mio; Nakao, Yusuke; Tsugane, Mamiko; Suzuki, Hiroaki; Oka, Jun-Ichiro; Yamashita, Chikamasa","year":2021,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 335, 575-583","doi":"10.1016/j.jconrel.2021.06.007","pmid":"34116136","tags":["glp-1-receptor-agonists","mental-health","drug-delivery"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"PAS-CPP-GLP-2 showed antidepressant-like effects within 20 min of intranasal administration at the same dose effective by i.c.v. injection, while i.v. delivery was ineffective. The modification prevented degradation and enabled transcellular nose-to-brain transport.","whyItMatters":"Depression affects hundreds of millions of people, and treatment-resistant depression has few options. A nasal spray delivering an effective brain peptide within minutes could transform treatment — especially since GLP-2 works in treatment-resistant models where conventional antidepressants fail.","specificNumbers":"CPPs significantly enhanced nasal GLP-2 brain delivery; antidepressant effects in both depression and treatment-resistant depression models.","methodology":"In vitro: cellular uptake mechanism (macropinocytosis via CPP), endosomal escape (via PAS), and transcellular transport studies. In vivo: depression model mice tested with intranasal, intravenous, and intracerebroventricular PAS-CPP-GLP-2 administration.","limitations":"Mouse depression model — behavioral tests are proxies for human depression. Dose-response optimization and long-term efficacy not established. PAS-CPP modification adds manufacturing complexity. Safety profile of repeated intranasal delivery needs evaluation."},{"rthcId":"RPEP-05257","title":"The Protective Effects of Thymosin-β-4 in a Rat Model of Ischemic Acute Kidney Injury.","authors":"Aksu, Ugur; Yaman, Onur M; Guner, Ibrahim; Guntas, Gulcan; Sonmez, Fuat; Tanriverdi, Gamze; Eser, Mediha; Cakiris, Aris; Akyol, Sibel; Seçkin, İsmail; Uzun, Hafize; Yelmen, Nermin; Sahin, Gulderen","year":2021,"journal":"Journal of investigative surgery : the official journal of the Academy of Surgical Research, 34(6), 601-609","doi":"10.1080/08941939.2019.1672841","pmid":"31702404","tags":["thymosin-beta-4","kidney-health"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"Tβ4 significantly reduced caspase-9, MMP-9 activity, hyaluronan, oxidative stress, and inflammation markers while restoring antioxidant levels in both pre-treatment and peri-ischemic treatment groups. Serum creatinine and BUN were significantly reduced (p<0.001).","whyItMatters":"Ischemic AKI occurs commonly during surgery and in critical illness. Having an effective protective peptide that works even when given just before reperfusion could transform kidney injury prevention in clinical settings.","specificNumbers":"32 rats; 4 groups (8/group); 90-min ischemia; TB4 pre- and post-treatment both significantly reduced kidney damage.","methodology":"Rat model: 4 groups (n=8): sham, I/R (90 min ischemia + 3h reperfusion), Tβ4 pre-treatment + I/R, and Tβ4 during I/R. Measured renal function (Cr, BUN), histology, oxidative stress panel, inflammatory cytokines, caspase-9, MMP-9, and hyaluronan.","limitations":"Rat model with relatively short reperfusion period (3h). Long-term kidney recovery not assessed. Optimal human dosing and timing need investigation. Tβ4 is not yet approved for clinical use."},{"rthcId":"RPEP-05258","title":"Changes in endogenous oxytocin levels after intranasal oxytocin treatment in adult men with autism: An exploratory study with long-term follow-up.","authors":"Alaerts, Kaat; Steyaert, Jean; Vanaudenaerde, Bart; Wenderoth, Nicole; Bernaerts, Sylvie","year":2021,"journal":"European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 43, 147-152","doi":"10.1016/j.euroneuro.2020.11.014","pmid":"33309460","tags":["oxytocin","mental-health"],"studyType":"human","evidenceStrength":"moderate","keyFinding":"Daily intranasal OT for 4 weeks increased endogenous salivary OT levels that persisted at 4-week follow-up. Increases were most pronounced in individuals with larger improvements in ASD social symptoms, suggesting a positive spiral of OT release.","whyItMatters":"If oxytocin treatment can kick-start a self-sustaining cycle of increased natural oxytocin production — especially linked to social improvement — it suggests treatment could have lasting benefits beyond the treatment period, addressing a key concern about peptide therapy dependency.","specificNumbers":"4-week double-blind RCT; endogenous salivary OT levels changed with treatment vs placebo.","methodology":"Double-blind, randomized, placebo-controlled study. 34 adult men with ASD received 4 weeks of daily intranasal OT (24 IU) or placebo. Salivary OT measured before, after, and at 4-week and 1-year follow-up. Between-subject design.","limitations":"Small sample size (34 participants). Only male adults with ASD studied. Saliva OT levels may not perfectly reflect brain OT activity. Mechanism of endogenous OT increase is inferred, not directly demonstrated."},{"rthcId":"RPEP-05259","title":"Design of an epitope-based peptide vaccine against the SARS-CoV-2: a vaccine-informatics approach.","authors":"Alam, Aftab; Khan, Arbaaz; Imam, Nikhat; Siddiqui, Mohd Faizan; Waseem, Mohd; Malik, Md Zubbair; Ishrat, Romana","year":2021,"journal":"Briefings in bioinformatics, 22(2), 1309-1323","doi":"10.1093/bib/bbaa340","pmid":"33285567","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05260","title":"Lessons from a Single Amino Acid Substitution: Anticancer and Antibacterial Properties of Two Phospholipase A2-Derived Peptides.","authors":"Almeida, José R; Mendes, Bruno; Lancellotti, Marcelo; Franchi, Gilberto C; Passos, Óscar; Ramos, Maria J; Fernandes, Pedro A; Alves, Cláudia; Vale, Nuno; Gomes, Paula; da Silva, Saulo L","year":2021,"journal":"Current issues in molecular biology, 44(1), 46-62","doi":"10.3390/cimb44010004","pmid":"35723383","tags":["venom-derived-peptides","antimicrobial-peptides"],"studyType":"in_vitro","evidenceStrength":"preliminary","keyFinding":"Both p-AppK and p-Acl showed dual antibacterial (including MDR strains) and anticancer activity without hemolysis. The leucine→phenylalanine substitution in p-Acl significantly enhanced activity, particularly against osteosarcoma (HOS, MG63) cells.","whyItMatters":"A single amino acid change dramatically altering drug properties demonstrates how natural peptide variation can be leveraged for drug design. The dual cancer/infection-fighting activity without blood cell toxicity makes these promising therapeutic candidates.","specificNumbers":"Single Leu/Phe substitution; one peptide primarily antibacterial, the other primarily anticancer.","methodology":"Peptide synthesis and characterization. Antibacterial MIC testing against Gram-positive and Gram-negative bacteria including MDR strains. Anticancer cytotoxicity against solid and liquid tumors. Hemolysis assays. Molecular dynamics simulations for mechanism. DNA-intercalating dye uptake for membrane permeability.","limitations":"In vitro study only — no animal model testing. The relationship between membrane disruption in vitro and therapeutic potential in vivo is complex. Selectivity between cancer and normal cells beyond red blood cells not fully characterized."},{"rthcId":"RPEP-05261","title":"The efficacy and safety of animal-derived nootropics in cognitive disorders: Systematic review and meta-analysis.","authors":"Alsulaimani, Rayan A; Quinn, Terence J","year":2021,"journal":"Cerebral circulation - cognition and behavior, 2, 100012","doi":"10.1016/j.cccb.2021.100012","pmid":"36324709","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05262","title":"In vivo CRISPR-Cas9 knockout screening using quantitative PCR identifies thymosin beta-4 X-linked that promotes diffuse-type gastric cancer metastasis.","authors":"An, Hyeok-Won; Kim, Si-You; Kwon, Jong-Wan; Seok, Sang-Hyuk; Woo, Sang-Ho; Kim, Dae-Yong; Park, Jun Won","year":2021,"journal":"Molecular carcinogenesis, 60(9), 597-606","doi":"10.1002/mc.23326","pmid":"34081824","tags":["thymosin-beta-4","cancer-immunotherapy"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"Tmsb4x was identified via in vivo CRISPR screening as a promoter of DGC liver metastasis. It enhanced clonogenicity and anoikis resistance. E-cadherin deficiency upregulated Tmsb4x via Wnt signaling in stomach organoids.","whyItMatters":"Diffuse gastric cancer is highly metastatic with poor prognosis. Identifying Tmsb4x as a metastasis driver through unbiased CRISPR screening provides a new therapeutic target and reveals a connection between E-cadherin loss and peptide-mediated metastasis.","specificNumbers":"30 candidate genes screened; TMSB4X identified as key metastasis driver by in vivo CRISPR-Cas9 knockout.","methodology":"In vivo CRISPR-Cas9 knockout screening of 30 candidate genes in mouse DGC models (Smad4/p53/E-cadherin deficient). Splenic transplantation for liver metastasis. qPCR-based screening. Organoid culture. In situ hybridization for expression analysis.","limitations":"Mouse DGC model with specific genetic backgrounds (Smad4/p53/E-cadherin deletion) may not represent all human DGC. The therapeutic implications of targeting Tmsb4x in cancer need to be balanced against its beneficial roles in normal tissue repair."},{"rthcId":"RPEP-05263","title":"Bioactive Peptides as Potential Nutraceuticals for Diabetes Therapy: A Comprehensive Review.","authors":"Antony, Priya; Vijayan, Ranjit","year":2021,"journal":"International journal of molecular sciences, 22(16)","doi":"10.3390/ijms22169059","pmid":"34445765","tags":["general-peptide-science","antioxidant-peptides"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Food-derived bioactive peptides from various dietary sources demonstrate antidiabetic activity through blood glucose reduction, improved insulin uptake, and inhibition of DPP-IV and α-glucosidase enzymes in in vitro and in vivo studies.","whyItMatters":"With diabetes prevalence rising globally and nutrition being a modifiable risk factor, identifying specific food-derived peptides with antidiabetic properties could lead to targeted dietary recommendations and nutraceutical development.","specificNumbers":"Multiple food sources produce DPP-IV inhibitory, alpha-glucosidase inhibitory, and insulin-sensitizing peptides.","methodology":"Comprehensive review of recent literature on food-derived bioactive peptides with antidiabetic activity, covering in vitro enzyme inhibition studies, cell-based assays, and animal model studies across multiple food protein sources.","limitations":"Most evidence is from in vitro and animal studies — human clinical evidence is limited. Oral bioavailability of food peptides remains a significant challenge. The effective doses in studies may differ from amounts achievable through normal diet."},{"rthcId":"RPEP-05264","title":"A Global Review on Short Peptides: Frontiers and Perspectives.","authors":"Apostolopoulos, Vasso; Bojarska, Joanna; Chai, Tsun-Thai; Elnagdy, Sherif; Kaczmarek, Krzysztof; Matsoukas, John; New, Roger; Parang, Keykavous; Lopez, Octavio Paredes; Parhiz, Hamideh; Perera, Conrad O; Pickholz, Monica; Remko, Milan; Saviano, Michele; Skwarczynski, Mariusz; Tang, Yefeng; Wolf, Wojciech M; Yoshiya, Taku; Zabrocki, Janusz; Zielenkiewicz, Piotr; AlKhazindar, Maha; Barriga, Vanessa; Kelaidonis, Konstantinos; Sarasia, Elham Mousavinezhad; Toth, Istvan","year":2021,"journal":"Molecules (Basel, Switzerland), 26(2)","doi":"10.3390/molecules26020430","pmid":"33467522","tags":["general-peptide-science","peptide-chemistry"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Short peptides have evolved from simple hormone replacements to versatile therapeutic platforms including cell-penetrating agents, vaccines, drug delivery systems, aptamers, and smart biomaterials, with continued advances in synthesis and computational design.","whyItMatters":"This landmark review provides the most comprehensive overview of where peptide therapeutics stand after a century of development and where the field is heading, making it essential reading for anyone in peptide science.","specificNumbers":"Growing peptide clinical pipeline; applications in therapeutics, diagnostics, delivery, and biomaterials.","methodology":"Comprehensive multi-author global review covering current state-of-the-art in short peptide therapeutics, synthesis, delivery, and applications across multiple disease areas.","limitations":"Broad scope necessarily limits depth on individual topics. Rapid advances since publication may have already shifted some frontiers. Some sections may reflect regional biases despite global authorship."},{"rthcId":"RPEP-05265","title":"Peptide functionalized liposomes for receptor targeted cancer therapy.","authors":"Aronson, Matthew R; Medina, Scott H; Mitchell, Michael J","year":2021,"journal":"APL bioengineering, 5(1), 011501","doi":"10.1063/5.0029860","pmid":"33532673","tags":["peptide-drug-conjugates","cancer-therapy"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Peptides with fewer than 30 amino acids can be attached to the surface of liposomes (tiny fat-based delivery capsules) to guide chemotherapy drugs directly to tumors. These peptide-functionalized liposomes work by recognizing receptor proteins that are overexpressed on cancer cells, enabling active tumor targeting rather than relying on passive accumulation.\n\nThe review covers targeting strategies for multiple aggressive cancers including glioblastoma, pancreatic, lung, and breast cancer, each exploiting different receptors overexpressed on their tumor surfaces. While standard liposomal drugs like Doxil reduce toxicity by passive targeting (the EPR effect), adding peptide ligands enables active homing that can significantly improve tumor-specific drug delivery.","whyItMatters":"Chemotherapy drugs kill cancer cells but also damage healthy tissue, causing severe side effects. Liposomal encapsulation helped reduce toxicity, but passive targeting wasn't enough. Adding peptides as homing signals represents the next evolution — smart delivery vehicles that actively seek out tumors. This approach could make chemotherapy more effective at lower doses with fewer side effects across some of the hardest-to-treat cancers.","specificNumbers":"peptides <30 amino acids · targets glioblastoma, pancreatic, lung, breast cancers · covalent and electrostatic functionalization methods","methodology":"Comprehensive review of published research on peptide-functionalized liposomes, covering surface modification techniques, receptor-targeting strategies, and applications across multiple tumor types.","limitations":"As a review, this synthesizes existing preclinical and early clinical research. Many peptide-functionalized liposome systems are still in preclinical stages, and the translation from laboratory targeting to clinical efficacy involves significant challenges including manufacturing scalability and in-vivo stability of the peptide ligands."},{"rthcId":"RPEP-05266","title":"Advanced trends in protein and peptide drug delivery: a special emphasis on aquasomes and microneedles techniques.","authors":"Asfour, Marwa Hasanein","year":2021,"journal":"Drug delivery and translational research, 11(1), 1-23","doi":"10.1007/s13346-020-00746-z","pmid":"32337668","tags":["drug-delivery","general-peptide-science"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Aquasomes enhance peptide stability through ceramic core-polyhydroxy oligomer coating for oral delivery. Microneedles (150-1500 μm) create transdermal pathways for peptide drugs. Both approaches address the key barriers of oral degradation and skin impermeability.","whyItMatters":"Patient compliance with injectable peptide drugs is a major clinical challenge. Alternative delivery routes could make peptide therapeutics more accessible and improve treatment adherence, especially for conditions requiring daily dosing.","specificNumbers":"Aquasomes preserve peptide activity; microneedles enable painless transdermal delivery at micrometer scale.","methodology":"Review of recent advances in peptide drug delivery focusing on oral and transdermal routes, with detailed discussion of aquasome nanoparticle design and microneedle technology types and mechanisms.","limitations":"Review of technologies at various development stages — many not yet clinically validated. Scale-up manufacturing challenges for both aquasomes and microneedles. Regulatory pathways for novel delivery devices are complex."},{"rthcId":"RPEP-05267","title":"Dairy bioactive proteins and peptides: a narrative review.","authors":"Auestad, Nancy; Layman, Donald K","year":2021,"journal":"Nutrition reviews, 79(Suppl 2), 36-47","doi":"10.1093/nutrit/nuab097","pmid":"34879145","tags":["general-peptide-science","antimicrobial-peptides"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Dairy proteins and their encrypted bioactive peptides exhibit diverse bioactivities including antimicrobial, satiety, mineral-binding, and anti-lipidemic properties. Individual protein fractions (caseins, whey proteins) have distinct bioactivity profiles.","whyItMatters":"Understanding the specific bioactive peptides in milk could guide dairy product development, infant formula optimization, and nutraceutical design — moving beyond general 'milk is good for you' to specific functional benefits.","specificNumbers":"Casein and whey proteins release peptides with satiety, antimicrobial, mineral-binding, and anti-lipidemic properties.","methodology":"Narrative review of the current science on dairy protein and peptide contributions to human health, covering individual protein fractions and their released bioactive peptides.","limitations":"Narrative review without systematic methodology. Many bioactive peptide effects demonstrated in vitro may not translate to meaningful clinical benefits at dietary intake levels. Individual variation in digestion affects peptide release."},{"rthcId":"RPEP-05268","title":"Identification of HLA-A*0201-restricted CTL Epitopes for MLAA-34-specific Immunotherapy for Acute Monocytic Leukemia.","authors":"Bai, Ju; Wang, Jianli; Yang, Yun; Wang, Fangxia; He, Aili; Zhang, Wanggang","year":2021,"journal":"Journal of immunotherapy (Hagerstown, Md. : 1997), 44(4), 141-150","doi":"10.1097/CJI.0000000000000350","pmid":"33596023","tags":["cancer-immunotherapy"],"studyType":"in_vitro","evidenceStrength":"moderate","keyFinding":"MLAA-34236-244 (ILDRHNFAI) showed strongest HLA-A*0201 binding, induced specific CTL responses, inhibited tumor growth, and improved survival in leukemia-bearing humanized SCID mice with favorable cytokine profiles.","whyItMatters":"Acute monocytic leukemia has limited targeted therapy options. Identifying a specific peptide vaccine target unique to this cancer type could enable personalized immunotherapy for a disease with poor prognosis.","specificNumbers":"10 epitopes predicted; 3 (positions 324-332, 293-301, 236-244) strongly activated CTLs and killed leukemia cells.","methodology":"Bioinformatic epitope prediction from MLAA-34 protein. HLA-A*0201 binding assays. Tetramer staining. IFN-γ ELISPOT. Cytotoxicity assays against THP-1 cells. In vivo vaccine testing in humanized SCID mice. CD8+ vs CD4+ T cell killing comparison.","limitations":"HLA-A*0201 restriction limits applicability to patients with this allele. Humanized SCID mouse model doesn't fully recapitulate human immune responses. Translation from mouse model to clinical leukemia treatment requires human trials."},{"rthcId":"RPEP-05269","title":"Immune-based mutation classification enables neoantigen prioritization and immune feature discovery in cancer immunotherapy.","authors":"Bai, Peng; Li, Yongzheng; Zhou, Qiuping; Xia, Jiaqi; Wei, Peng-Cheng; Deng, Hexiang; Wu, Min; Chan, Sanny K; Kappler, John W; Zhou, Yu; Tran, Eric; Marrack, Philippa; Yin, Lei","year":2021,"journal":"Oncoimmunology, 10(1), 1868130","doi":"10.1080/2162402X.2020.1868130","pmid":"33537173","tags":["cancer-immunotherapy"],"studyType":"in_vitro","evidenceStrength":"moderate","keyFinding":"The 'NP rule' — conservative mutant orientation of anchor residues in immunogenic neoantigens — improved neoantigen prioritization when integrated with existing prediction algorithms. Structural analysis showed these mutations enhance both MHC binding and TCR recognition.","whyItMatters":"Better neoantigen prediction means more effective cancer vaccines with fewer wasted targets. The NP rule provides a biologically grounded filter that complements computational approaches.","specificNumbers":"3-category classification; improved neoantigen prioritization; novel immune features identified; correlated with therapy response.","methodology":"Classification of human neoantigen data into three categories based on TCR-pMHC binding events. Integration of NP rule with existing prediction algorithms. X-ray crystallography of neoantigen/MHC structures for mechanistic understanding.","limitations":"The NP rule may not capture all immunogenic neoantigens. Limited to HLA types with available structural data. The improvement in prediction, while significant, still leaves room for false positives and negatives."},{"rthcId":"RPEP-05270","title":"Regulatory T Cells in Bioactive Peptides-Induced Oral Tolerance; a Two-Edged Sword Related to the Risk of Chronic Diseases: A Systematic Review.","authors":"Barati, Meisam; Jabbari, Masoumeh; Nickho, Hamid; Esparvarinha, Mojgan; Javadi Mamaghani, Amirreza; Majdi, Hasan; Fathollahi, Anwar; Davoodi, Sayed Hossein","year":2021,"journal":"Nutrition and cancer, 73(6), 956-967","doi":"10.1080/01635581.2020.1784442","pmid":"32648489","tags":["collagen-peptides","immune-system"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Oral bioactive peptides improve multiple diseases via T-reg expansion, and collagen hydrolysate supplementation reduces OA pain. However, higher circulating T-regs are associated with reduced CVD/allergy risk but increased solid cancer risk.","whyItMatters":"As collagen peptide and bioactive peptide supplements grow in popularity, understanding their immune effects — both beneficial and potentially harmful — is critical for safe long-term use recommendations.","specificNumbers":"3,081 papers identified; collagen induces T-reg oral tolerance; benefits for OA established; theoretical immune concerns raised.","methodology":"Systematic review searching PubMed and Scopus. 3081 papers identified, 22 included: 12 on BP-induced oral tolerance, 6 on collagen hydrolysate for OA, and 4 observational studies on T-regs and chronic disease risk.","limitations":"Systematic review but with heterogeneous study designs and mostly animal data for tolerance induction. Cancer risk association is observational and causation isn't established. T-reg subtypes and their specific roles weren't distinguished."},{"rthcId":"RPEP-05271","title":"Circulating LEAP-2 is associated with puberty in girls.","authors":"Barja-Fernández, Silvia; Lugilde, Javier; Castelao, Cecilia; Vázquez-Cobela, Rocío; Seoane, Luisa M; Diéguez, Carlos; Leis, Rosaura; Tovar, Sulay","year":2021,"journal":"International journal of obesity (2005), 45(3), 502-514","doi":"10.1038/s41366-020-00703-3","pmid":"33139887","tags":["antimicrobial-peptides","growth-hormone-peptides"],"studyType":"human","evidenceStrength":"moderate","keyFinding":"LEAP-2 is significantly higher in girls vs. boys regardless of obesity status. In girls, LEAP-2 increases significantly during puberty (p<0.001) and correlates positively with insulin, IGF-1, HOMA-IR, triglycerides and negatively with ghrelin.","whyItMatters":"Understanding LEAP-2's role in puberty could reveal new mechanisms behind sex differences in appetite, metabolism, and pubertal timing. Given LEAP-2's ghrelin-blocking function, this has implications for understanding childhood obesity and pubertal disorders.","specificNumbers":"LEAP-2 associated with puberty in girls; modulated by nutritional status; LEAP-2 is endogenous GHSR1a antagonist.","methodology":"Cross-sectional study of 150 lean and obese children and adolescents. Plasma LEAP-2 measured with comparison by sex, pubertal stage, and body weight. Correlation analysis with metabolic hormones and markers.","limitations":"Cross-sectional design cannot establish causation or temporal relationships. Relatively small sample for subgroup analyses. Plasma LEAP-2 levels may not reflect tissue-specific activity. Only one ethnic group studied."},{"rthcId":"RPEP-05272","title":"Ghrelin receptor agonist hexarelin attenuates antinociceptive tolerance to morphine in rats.","authors":"Baser, Tayfun; Ozdemir, Ercan; Filiz, Ahmet Kemal; Taskiran, Ahmet Sevki; Gursoy, Sinan","year":2021,"journal":"Canadian journal of physiology and pharmacology, 99(5), 461-467","doi":"10.1139/cjpp-2020-0218","pmid":"32893668","tags":["growth-hormone-peptides","pain-management"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"Hexarelin (0.2 mg/kg) combined with morphine attenuated analgesic tolerance and enhanced antinociception in tail-flick and hot-plate tests. The GHS-R antagonist [d-Lys3]-GHRP-6 showed no significant effect on morphine tolerance.","whyItMatters":"Morphine tolerance forces dose escalation, increasing side effects and addiction risk. A peptide that can maintain morphine's effectiveness at lower doses could improve pain management while reducing opioid-related harms.","specificNumbers":"104 rats; hexarelin attenuated morphine tolerance; [D-Lys3]-GHRP-6 had no effect; tested by tail-flick and hot plate.","methodology":"104 Wistar rats. Three-day cumulative morphine dosing regimen to induce tolerance. Day 4 assessment of tolerance with hexarelin, GHS-R antagonist, and morphine combinations. Tail-flick and hot-plate analgesic tests at 30-min intervals.","limitations":"Acute tolerance model in rats — may not fully replicate chronic tolerance in human patients. Mechanism by which hexarelin attenuates tolerance not fully elucidated. Clinical applicability and dosing for humans unknown."},{"rthcId":"RPEP-05273","title":"Bile acid transporter-mediated oral absorption of insulin via hydrophobic ion-pairing approach.","authors":"Bashyal, Santosh; Seo, Jo-Eun; Choi, Young Wook; Lee, Sangkil","year":2021,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 338, 644-661","doi":"10.1016/j.jconrel.2021.08.060","pmid":"34481926","tags":["drug-delivery","general-peptide-science"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"Insulin-SGDC nanocomplexes achieved 6.44% pharmacological availability via jejunal administration through ASBT-mediated active transport. Jejunal delivery was 17.89-fold more effective than colonic. Caco-2 permeability improved 6.36-fold vs. insulin solution.","whyItMatters":"Replacing insulin injections with oral formulations would transform diabetes management for millions of patients. Exploiting an existing active transport system rather than trying to force passive absorption is an innovative strategy.","specificNumbers":"HIP of insulin + SGDC; markedly improved intestinal absorption via bile acid transporters vs free insulin.","methodology":"Hydrophobic ion-pairing of insulin with sodium glycodeoxycholate. Optimization and characterization. Caco-2 permeability studies with endocytosis inhibitors. ASBT-transfected MDCK cells for transport confirmation. In vivo intrajejunal and intracolonic administration in rats.","limitations":"Rat intrajejunal delivery doesn't replicate oral administration with gastric transit. 6.44% bioavailability, while improved, may not be sufficient for clinical use. Manufacturing scalability and stability need assessment. Human ASBT capacity and variability could affect performance."},{"rthcId":"RPEP-05274","title":"Introducing a delivery system for melanogenesis inhibition in melanoma B16F10 cells mediated by the conjugation of tyrosine ammonia-lyase and a TAT-penetrating peptide.","authors":"Behzadipour, Yasaman; Sadeghian, Issa; Ghaffarian Bahraman, Ali; Hemmati, Shiva","year":2021,"journal":"Biotechnology progress, 37(1), e3071","doi":"10.1002/btpr.3071","pmid":"32840065","tags":["drug-delivery","cosmetic-peptides"],"studyType":"in_vitro","evidenceStrength":"preliminary","keyFinding":"TAT-RsTAL fusion protein successfully entered B16F10 melanocytes and inhibited melanin biosynthesis in a time-dependent manner (12.7% at 24h, 28.2% at 48h, 33.9% at 72h) with no significant effect on cell viability up to 100 μg/mL.","whyItMatters":"Current depigmenting agents often work by inhibiting tyrosinase, which can be toxic or ineffective. This substrate-depletion strategy using a cell-penetrating peptide delivery system offers a fundamentally different and potentially safer approach.","specificNumbers":"TAT-tyrosinase conjugate reduced melanin production by L-tyrosine substrate competition in B16F10 cells.","methodology":"Recombinant expression of TAT-RsTAL fusion protein. Fluorescence microscopy tracking of cell entry (30-180 min). Intracellular enzyme activity measurement. Melanin quantification in B16F10 cells over 24-72h. Cytotoxicity assessment.","limitations":"In vitro study using melanoma cells — normal melanocyte response may differ. Maximum 33.9% melanin reduction may not be sufficient for clinical hyperpigmentation treatment. Stability and repeated dosing not assessed. Manufacturing of protein-peptide conjugates is complex."},{"rthcId":"RPEP-05275","title":"Prebiotic Inulin and Sodium Butyrate Attenuate Obesity-Induced Intestinal Barrier Dysfunction by Induction of Antimicrobial Peptides.","authors":"Beisner, Julia; Filipe Rosa, Louisa; Kaden-Volynets, Valentina; Stolzer, Iris; Günther, Claudia; Bischoff, Stephan C","year":2021,"journal":"Frontiers in immunology, 12, 678360","doi":"10.3389/fimmu.2021.678360","pmid":"34177920","tags":["antimicrobial-peptides","gut-health"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"Inulin and butyrate restored WSD-impaired Paneth cell α-defensin and MMP7 expression, induced colonic β-defensin-1 and tight junction genes, improved intestinal permeability, reduced endotoxemia, and attenuated hepatosteatitis. Mechanism involved SCFA-mediated STAT3 activation and histone deacetylation.","whyItMatters":"The gut barrier is a critical link between diet, obesity, and metabolic disease. Showing that prebiotics restore antimicrobial peptide defense provides a mechanism for their health benefits and supports dietary fiber as a therapeutic intervention for obesity-related gut damage.","specificNumbers":"10% inulin or 5% butyrate; increased AMP expression; improved gut barrier; reduced endotoxin translocation and liver steatosis.","methodology":"C57BL/6 mice fed control or Western-style diet ± fructose ± 10% inulin or 5% sodium butyrate for 12 weeks. Measured weight, liver triglycerides, intestinal permeability, endotoxemia, antimicrobial peptide expression. Organoid cultures for mechanistic studies with SCFA.","limitations":"Mouse model — human gut antimicrobial peptide regulation may differ. Specific dietary formulations may not directly translate to human supplement recommendations. Long-term effects and optimal dosing not established."},{"rthcId":"RPEP-05276","title":"First-in-Class Cyclic Temporin L Analogue: Design, Synthesis, and Antimicrobial Assessment.","authors":"Bellavita, Rosa; Casciaro, Bruno; Di Maro, Salvatore; Brancaccio, Diego; Carotenuto, Alfonso; Falanga, Annarita; Cappiello, Floriana; Buommino, Elisabetta; Galdiero, Stefania; Novellino, Ettore; Grossmann, Tom N; Mangoni, Maria Luisa; Merlino, Francesco; Grieco, Paolo","year":2021,"journal":"Journal of medicinal chemistry, 64(15), 11675-11694","doi":"10.1021/acs.jmedchem.1c01033","pmid":"34296619","tags":["antimicrobial-peptides","peptide-chemistry"],"studyType":"in_vitro","evidenceStrength":"moderate","keyFinding":"First-in-class cyclic temporin L analogues were created using lactam, triazole, hydrocarbon, and disulfide linkers. The library revealed relationships between α-helical content and antimicrobial, antibiofilm, and cytotoxic activities.","whyItMatters":"Antimicrobial resistance demands new antibiotics. Cyclization solves the stability problem of natural antimicrobial peptides while the systematic structure-activity analysis provides a blueprint for optimizing future AMP candidates.","specificNumbers":"3 cyclization strategies; increased α-helicity; retained broad antimicrobial activity; first cyclic temporin reported.","methodology":"Peptide design and synthesis with four cyclization strategies. Structural characterization for α-helicity. Antimicrobial activity testing. Antibiofilm assays. Cytotoxicity evaluation. Structure-activity relationship analysis.","limitations":"In vitro study — in vivo stability, pharmacokinetics, and therapeutic efficacy not assessed. Cyclization may alter selectivity between bacterial and human cell membranes. Manufacturing complexity increases with cyclization."},{"rthcId":"RPEP-05277","title":"Thymosin alpha 1 exerts beneficial extrapulmonary effects in cystic fibrosis.","authors":"Bellet, Marina M; Borghi, Monica; Pariano, Marilena; Renga, Giorgia; Stincardini, Claudia; D'Onofrio, Fiorella; Brancorsini, Stefano; Garaci, Enrico; Costantini, Claudio; Romani, Luigina","year":2021,"journal":"European journal of medicinal chemistry, 209, 112921","doi":"10.1016/j.ejmech.2020.112921","pmid":"33071052","tags":["thymosin-alpha-1"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"Tα1 restored barrier integrity and immune homeostasis in inflamed CF mouse gut, protected pancreas and liver, and showed similar benefits in a metabolic syndrome model relevant to CF patients with high caloric intake.","whyItMatters":"As CF patients live longer due to new lung therapies (CFTR modulators), extra-pulmonary complications become increasingly important. Tα1's multi-organ anti-inflammatory effects could address gastrointestinal, hepatic, and pancreatic symptoms that significantly affect quality of life.","specificNumbers":"TA1 restored CFTR function and reduced inflammation in GI, hepatobiliary, and pancreatic CF manifestations.","methodology":"Murine models of gut inflammation with clinical relevance for CF patients, including CF mice and metabolic syndrome mice. Assessed intestinal barrier integrity, immune homeostasis, and pancreatic/hepatic inflammation.","limitations":"Mouse models of CF and metabolic syndrome may not fully replicate human disease. Specific mechanisms of barrier protection not fully elucidated. Dosing, timing, and route optimization for human CF patients needed."},{"rthcId":"RPEP-05278","title":"What Is the Mechanism Driving the Reduction of Cardiovascular Events from Glucagon-like Peptide-1 Receptor Agonists?-A Mini Review.","authors":"Berndt, Jared; Ooi, Soo Liang; Pak, Sok Cheon","year":2021,"journal":"Molecules (Basel, Switzerland), 26(16)","doi":"10.3390/molecules26164822","pmid":"34443410","tags":["glp-1-receptor-agonists","cardiovascular-health"],"studyType":"review","evidenceStrength":"strong","keyFinding":"GLP-1 receptor agonists reduce major adverse cardiovascular events (MACE), but improvements in traditional risk markers only partially account for this benefit, suggesting direct anti-atherogenic mechanisms.","whyItMatters":"Understanding how GLP-1 drugs protect the heart could help optimize their use in high-risk patients and guide development of next-generation therapies targeting the same pathways.","specificNumbers":"GLP-1 RAs reduce MACE; mechanisms: anti-inflammatory, anti-atherosclerotic, endothelial-protective, cardioprotective.","methodology":"Mini review of published clinical trials and mechanistic studies on GLP-1 receptor agonists and cardiovascular outcomes.","limitations":"As a mini review, this paper provides a narrative synthesis rather than a systematic or quantitative meta-analysis. The exact mechanisms remain incompletely understood."},{"rthcId":"RPEP-05279","title":"The right immune-modulation at the right time: thymosin α1 for prevention of severe COVID-19 in cancer patients.","authors":"Bersanelli, Melissa; Giannarelli, Diana; Leonetti, Alessandro; Buti, Sebastiano; Tiseo, Marcello; Nouvenne, Antonio; Ticinesi, Andrea; Meschi, Tiziana; Procopio, Giuseppe; Danielli, Riccardo","year":2021,"journal":"Future oncology (London, England), 17(9), 1097-1104","doi":"10.2217/fon-2020-0754","pmid":"33538178","tags":["thymosin-alpha-1","immune-system"],"studyType":"human","evidenceStrength":"preliminary","keyFinding":"Thymosin α1 has a strong theoretical basis for preventing severe COVID-19 in immunocompromised cancer patients, supported by its known immune-modulating properties, leading to a Phase II randomized clinical trial.","whyItMatters":"Cancer patients face disproportionately high risks from COVID-19 and often mount weaker vaccine responses. A prophylactic peptide therapy could provide an additional layer of protection for this vulnerable population.","specificNumbers":"Phase II randomized study; PROTHYMOS (Eudract 2020-006020-13); TA1 for COVID-19 prophylaxis in cancer patients.","methodology":"Rationale paper describing the scientific basis and design for the PROTHYMOS study, a prospective, multicenter, open-label, Phase II randomized trial.","limitations":"This is a rationale paper rather than a results paper — the clinical trial was still in its start-up phase. Actual efficacy data was not yet available."},{"rthcId":"RPEP-05280","title":"Effect of 'pH' on the Rate of Pyroglutamate Formation in Solution and Lyophilized Solids.","authors":"Bersin, Lia M; Patel, Sajal M; Topp, Elizabeth M","year":2021,"journal":"Molecular pharmaceutics, 18(8), 3116-3124","doi":"10.1021/acs.molpharmaceut.1c00338","pmid":"34232660","tags":["peptide-chemistry"],"studyType":"in_vitro","evidenceStrength":"strong","keyFinding":"At pH 5.5-6 (the range commonly used for mAb formulations), pyroglutamate formation in lyophilized solids was faster than in solution, with markedly different pH-dependence profiles between the two states.","whyItMatters":"Understanding how peptide drugs degrade during storage is critical for developing stable formulations. The finding that freeze-drying doesn't always protect against degradation at common formulation pH values could change how pharmaceutical companies design peptide and antibody products.","specificNumbers":"Strong pH dependence in solution and solid state; buffer species affected reaction rate; first detailed solid-state study.","methodology":"Model peptide (EVQLVESGGGLVQPGGSLR) formulated at pH 4-9 in multiple buffer systems, lyophilized or kept in solution, stored at 50°C for 10+ weeks, with pGlu formation monitored by RP-HPLC.","limitations":"Used a single model peptide at accelerated storage conditions (50°C). Results may not directly translate to all peptides and proteins or real-world storage temperatures."},{"rthcId":"RPEP-05281","title":"Migraine therapeutics differentially modulate the CGRP pathway.","authors":"Bhakta, Minoti; Vuong, Trang; Taura, Tetsuya; Wilson, David S; Stratton, Jennifer R; Mackenzie, Kimberly D","year":2021,"journal":"Cephalalgia : an international journal of headache, 41(5), 499-514","doi":"10.1177/0333102420983282","pmid":"33626922","tags":["cgrp","neurological-peptides"],"studyType":"review","evidenceStrength":"strong","keyFinding":"CGRP ligand antibodies and receptor-targeting agents have distinct mechanisms: receptor antibodies and gepants block multiple peptides and receptors, while ligand antibodies selectively block only CGRP signaling.","whyItMatters":"Understanding these mechanistic differences helps explain why patients may respond differently to various CGRP-targeting migraine drugs and could guide treatment selection for individual patients.","specificNumbers":"6 approved drugs: 3 anti-CGRP mAbs, 1 anti-receptor mAb, 2 gepants; distinct CGRP pathway modulation mechanisms.","methodology":"In vitro comparison using binding assays, cAMP functional assays, and imaging/internalization assays with human CGRP and AMY1 receptors.","limitations":"In vitro study that may not fully capture the complexity of in vivo pharmacology. Clinical implications of these mechanistic differences remain to be confirmed in head-to-head clinical trials."},{"rthcId":"RPEP-05282","title":"Lactoferrin-derived peptides antimicrobial activity: an in vitro experiment.","authors":"Biasibetti, Elena; Rapacioli, Silvia; Bruni, Natascia; Martello, Elisa","year":2021,"journal":"Natural product research, 35(24), 6073-6077","doi":"10.1080/14786419.2020.1821017","pmid":"32927978","tags":["lactoferrin","antimicrobial-peptides"],"studyType":"in_vitro","evidenceStrength":"preliminary","keyFinding":"Lactoferricin and lactoferrampin show synergistic antimicrobial effects when combined, and their activity is further enhanced by natural plant extracts.","whyItMatters":"As antibiotic resistance grows, natural antimicrobial peptides from common sources like milk could offer alternative approaches to treating moderate infections, either alone or as adjuncts to existing therapies.","specificNumbers":"Lfc and Lfa active alone; synergistic combinations identified (FIC <0.5); enhanced activity with natural extracts.","methodology":"In vitro antimicrobial testing using Minimum Inhibitory Concentration (MIC) and Fractional Inhibitory Concentration (FIC) index measurements against three pathogen species.","limitations":"In vitro study only — results may not directly translate to in vivo efficacy. The specific natural extracts used were not detailed in the abstract. Tested against only three pathogen species."},{"rthcId":"RPEP-05283","title":"Novel insight into Robert's cytoprotection: complex therapeutic effect of cytoprotective pentadecapeptide pentadecapeptide BPC 157 in rats with perforated stomach throughout modulation of nitric oxide-system. Comparison with L-arginine, ranitidine and pantoprazole therapy and L-NG-nitro-L-arginine methyl ester worsening.","authors":"Bilic, Z; Gojkovic, S; Kalogjera, L; Krezic, I; Malekinusic, D; Knezevic, M; Sever, M; Lojo, N; Kokot, A; Kasnik, K; Kralj, T; Vukojevic, J; Siroglavic, M; Peklic, M; Drmic, D; Milavic, M; Sikiric, S; Skorak, I; Brizic, I; Hriberski, K; Kubat, M; Vladic, J; Boban Blagaic, A; Tvrdeic, A; Skrtic, A; Seiwerth, S; Sikiric, P","year":2021,"journal":"Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 72(6)","doi":"10.26402/jpp.2021.6.11","pmid":"35485358","tags":["bpc-157","gut-health","wound-healing"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"BPC 157 at 0.01 μg/kg achieved complete healing of perforated stomach injuries by day 7 through rapid vascular restoration and NO-system modulation, outperforming pantoprazole and ranitidine.","whyItMatters":"Stomach perforation is a surgical emergency with significant morbidity. A peptide that can rapidly restore blood flow and promote healing through non-surgical means could complement existing treatments for gastrointestinal injuries.","specificNumbers":"10 mL abdominal bath at 1 min post-perforation; vascular restoration in 1-15 min; reduced adhesions and defect at day 7.","methodology":"Rat model with surgically perforated stomachs. Agents applied as abdominal bath at 1 min post-injury. Vascular, bleeding, and defect healing assessed at 1-15 min, day 1, and day 7. Gene expression (Cox2, VEGFa, Nos1-3, Nkap) and biochemical markers (MDA, NO) measured.","limitations":"Animal study in rats — results may not directly translate to humans. The perforated stomach model is surgically induced, which may differ from clinical perforations. No human clinical trial data available for this application."},{"rthcId":"RPEP-05284","title":"Expression of antimicrobial peptide genes oscillates along day/night rhythm protecting mice skin from bacteria.","authors":"Bilska, Bernadetta; Zegar, Aneta; Slominski, Andrzej T; Kleszczyński, Konrad; Cichy, Joanna; Pyza, Elzbieta","year":2021,"journal":"Experimental dermatology, 30(10), 1418-1427","doi":"10.1111/exd.14229","pmid":"33131146","tags":["antimicrobial-peptides","ll-37","skin-repair","immune-function","sleep"],"studyType":"animal","evidenceStrength":"preliminary","keyFinding":"Antimicrobial peptide gene expression in skin oscillates along day/night rhythms with two distinct patterns: activity-phase peptides controlled by light and sleep-phase peptides controlled by an internal circadian clock.","whyItMatters":"Understanding that skin antimicrobial defenses have daily rhythms could influence the timing of wound care, drug application, and surgical procedures to optimize healing and infection prevention.","specificNumbers":"5 AMP genes; 3 peaked at ~4h into dark; 2 peaked during sleep; 12:12 LD cycle","methodology":"Mouse study measuring mRNA expression of five antimicrobial peptide genes in skin under 12:12 light/dark cycles and constant darkness conditions, with bacterial survival experiments on skin at specific times.","limitations":"Mouse study — human skin AMP cycling patterns may differ. Limited number of AMP genes studied. Bacterial survival tested under controlled conditions that may not fully reflect natural exposure."},{"rthcId":"RPEP-05285","title":"Chronic oral nicotine administration and withdrawal regulate the expression of neuropeptide Y and its receptors in the mesocorticolimbic system.","authors":"Birdogan, Ali; Salur, Elif; Tuzcu, Fulya; Gokmen, Ramazan C; Ozturk Bintepe, Meliha; Aypar, Buket; Keser, Aysegul; Balkan, Burcu; Koylu, Ersin O; Kanit, Lutfiye; Gozen, Oguz","year":2021,"journal":"Neuropeptides, 90, 102184","doi":"10.1016/j.npep.2021.102184","pmid":"34425507","tags":["neuropeptides","addiction","anxiety-mood","receptor-signaling"],"studyType":"animal","evidenceStrength":"preliminary","keyFinding":"Nicotine withdrawal (24-48h) dramatically increased NPY and receptor (Y1, Y2, Y5) mRNA levels across the mesocorticolimbic system, suggesting NPY signaling upregulation as a compensatory response to withdrawal-induced negative affect.","whyItMatters":"Understanding the neurochemical changes during nicotine withdrawal could help develop better smoking cessation therapies, particularly ones targeting the NPY system to reduce withdrawal-associated anxiety and depression.","specificNumbers":"12 weeks nicotine; 25-50 mcg/mL dose; 24h and 48h withdrawal; NPY, Y1, Y2, Y5 mRNA increased","methodology":"Rats received oral nicotine (25-50 μg/ml) in drinking water for 12 weeks, then were withdrawn for 0, 24, or 48 hours. Brain NPY and receptor mRNA measured by qRT-PCR. Somatic withdrawal signs and locomotor activity assessed.","limitations":"Animal study using oral nicotine delivery, which differs from smoking. mRNA levels may not directly reflect peptide or protein levels. Limited to male rats in the study design details provided."},{"rthcId":"RPEP-05286","title":"Molecular Mechanisms of Staphylococcus and Pseudomonas Interactions in Cystic Fibrosis.","authors":"Biswas, Lalitha; Götz, Friedrich","year":2021,"journal":"Frontiers in cellular and infection microbiology, 11, 824042","doi":"10.3389/fcimb.2021.824042","pmid":"35071057","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05287","title":"Vitamin D Modulation of the Innate Immune Response to Paediatric Respiratory Pathogens Associated with Acute Lower Respiratory Infections.","authors":"Bleakley, Amy S; Licciardi, Paul V; Binks, Michael J","year":2021,"journal":"Nutrients, 13(1)","doi":"10.3390/nu13010276","pmid":"33478006","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05288","title":"Natural ghrelin in advanced cancer patients with cachexia, a case series.","authors":"Blum, David; de Wolf-Linder, Susanne; Oberholzer, Rolf; Brändle, Michael; Hundsberger, Thomas; Strasser, Florian","year":2021,"journal":"Journal of cachexia, sarcopenia and muscle, 12(2), 506-516","doi":"10.1002/jcsm.12659","pmid":"33452750","tags":["ghrp","cancer","weight-loss","hormone-optimization","clinical-trials"],"studyType":"case-series","evidenceStrength":"preliminary","keyFinding":"Subcutaneous ghrelin was safe without dose-limiting toxicity in advanced cancer cachexia patients, with positive effects on nutritional intake and subjective experience despite variable appetite responses.","whyItMatters":"Cancer cachexia affects up to 80% of advanced cancer patients and contributes to mortality. Finding safe, effective treatments to maintain nutrition and muscle mass could improve both quality of life and survival outcomes.","specificNumbers":"6 treated; 32 mcg/kg starting dose; 50% escalation; 88-day median survival; FAACT score decreased 6.8 points","methodology":"Dose-finding Phase I/II trial with subcutaneous natural ghrelin in advanced cancer patients with cachexia. Starting dose 32 μg/kg with 50% escalations. Self-injection twice daily for 4-day periods. Measurements: safety, nutritional intake, appetite scores, muscle mass, and strength over 6 weeks.","limitations":"Very small sample size (n=6 treated). All treated patients were male. Complex intervention design with multiple dose levels and washout periods. High attrition (only 3 completed the study). No control group."},{"rthcId":"RPEP-05289","title":"Real-World Evidence for Control of Chronic Migraine Patients Receiving CGRP Monoclonal Antibody Therapy Added to OnabotulinumtoxinA: A Retrospective Chart Review.","authors":"Blumenfeld, Andrew M; Frishberg, Benjamin M; Schim, Jack D; Iannone, Ashley; Schneider, Gary; Yedigarova, Larisa; Manack Adams, Aubrey","year":2021,"journal":"Pain and therapy, 10(2), 809-826","doi":"10.1007/s40122-021-00264-x","pmid":"33880725","tags":["neuropeptides","pain","clinical-trials","side-effects"],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"Combination of CGRP mAbs with onabotulinumtoxinA reduced monthly headache days by an additional 3.5-4.0 beyond Botox alone, with 45.1% achieving meaningful disability improvement.","whyItMatters":"Many chronic migraine patients don't achieve adequate relief from a single preventive therapy. This real-world evidence supports combining two different mechanism-based treatments for better outcomes.","specificNumbers":"257 patients; 21.5 MHDs pre-Botox; 12.1 pre-CGRP mAb; 3.5-4 MHD reduction; 45.1% MIDAS response; 78% erenumab; 28% adverse events","methodology":"Retrospective longitudinal chart review of 257 adults with chronic migraine at one clinical site, tracking outcomes at 3, 6, 9, and 12 months after adding CGRP mAb to ongoing Botox therapy.","limitations":"Retrospective design without a control group. Single clinical site. Predominantly erenumab (78%) with limited data on other mAbs. No randomization or blinding."},{"rthcId":"RPEP-05290","title":"GIP Receptor Agonism Attenuates GLP-1 Receptor Agonist-Induced Nausea and Emesis in Preclinical Models.","authors":"Borner, Tito; Geisler, Caroline E; Fortin, Samantha M; Cosgrove, Richard; Alsina-Fernandez, Jorge; Dogra, Mridula; Doebley, Sarah; Sanchez-Navarro, Marcos J; Leon, Rosa M; Gaisinsky, Jane; White, Arianna; Bamezai, Ankur; Ghidewon, Misgana Y; Grill, Harvey J; Crist, Richard C; Reiner, Benjamin C; Ai, Minrong; Samms, Ricardo J; De Jonghe, Bart C; Hayes, Matthew R","year":2021,"journal":"Diabetes, 70(11), 2545-2553","doi":"10.2337/db21-0459","pmid":"34380697","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05291","title":"Transient Permeation Enhancer® (TPE®) technology for oral delivery of octreotide: a technological evaluation.","authors":"Brayden, David J; Maher, Sam","year":2021,"journal":"Expert opinion on drug delivery, 18(10), 1501-1512","doi":"10.1080/17425247.2021.1942838","pmid":"34128734","tags":["oral-peptides","bioavailability","peptide-delivery","regulatory"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Oral octreotide using TPE technology achieved therapeutic endpoints in Phase III trials with ~0.7% relative oral bioavailability, requiring 20 mg capsules compared to 0.1 mg subcutaneous injections.","whyItMatters":"Successfully delivering a peptide drug orally is a major pharmaceutical achievement. This technology demonstrates that even with very low oral bioavailability, convenient oral peptide formulations can be clinically viable, opening doors for other peptide drugs.","specificNumbers":"20 mg capsule; 0.7% bioavailability; 200x subcutaneous dose; 2 Phase III trials; FDA approved 2020","methodology":"Technological evaluation reviewing the TPE platform, preclinical data, Phase I pharmacokinetics, and Phase III clinical trial results for oral octreotide (MYCAPSSA).","limitations":"Very low oral bioavailability (0.7%) means most of the drug is not absorbed. Requires high oral doses. The technology may not be applicable to all peptides. Patient adherence to twice-daily dosing versus monthly injections has trade-offs."},{"rthcId":"RPEP-05292","title":"Evaluation of the Safety of Calcitonin Gene-Related Peptide Antagonists for Migraine Treatment Among Adults With Raynaud Phenomenon.","authors":"Breen, Ilana D; Brumfiel, Caitlin M; Patel, Meera H; Butterfield, Richard J; VanderPluym, Juliana H; Griffing, Leroy; Pittelkow, Mark R; Mangold, Aaron R","year":2021,"journal":"JAMA network open, 4(4), e217934","doi":"10.1001/jamanetworkopen.2021.7934","pmid":"33871613","tags":["neuropeptides","pain","cardiovascular","side-effects","peptide-safety"],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"5.3% of migraine patients with Raynaud phenomenon experienced microvascular complications from CGRP antagonists, including rare but serious events like gangrene requiring digit amputation.","whyItMatters":"CGRP antagonists are highly effective migraine treatments, but their vasodilatory blockade poses theoretical risks for patients with vascular conditions. This study provides the first systematic safety data for this specific at-risk population.","specificNumbers":"169 patients; 9 (5.3%) complications; erenumab in 5, galcanezumab in 3, fremanezumab in 1; amputation in severe cases","methodology":"Retrospective cohort study at Mayo Clinic (May 2018 - September 2020) of 169 patients with both migraine and Raynaud phenomenon who received CGRP antagonist therapy.","limitations":"Retrospective single-center design. Small number of complication cases (n=9) limits statistical power for identifying risk factors. Potential ascertainment bias at a referral center."},{"rthcId":"RPEP-05293","title":"Oxytocin and Bone: Review and Perspectives.","authors":"Breuil, Véronique; Trojani, Marie-Charlotte; Ez-Zoubir, Amri","year":2021,"journal":"International journal of molecular sciences, 22(16)","doi":"10.3390/ijms22168551","pmid":"34445256","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05294","title":"Hunger and Satiety Peptides: Is There a Pattern to Classify Patients with Prader-Willi Syndrome?","authors":"Bueno, Marta; Boixadera-Planas, Ester; Blanco-Hinojo, Laura; Esteba-Castillo, Susanna; Giménez-Palop, Olga; Torrents-Rodas, David; Pujol, Jesús; Corripio, Raquel; Deus, Joan; Caixàs, Assumpta","year":2021,"journal":"Journal of clinical medicine, 10(21)","doi":"10.3390/jcm10215170","pmid":"34768690","tags":["neuropeptides","glp-1","weight-loss","hormone-optimization"],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"Cluster analysis separated PWS patients (23/27) into a distinct group with paradoxically elevated levels of both hunger (ghrelin) and satiety (leptin, PYY, GIP, GLP-1) hormones, suggesting hormonal dysfunction rather than simple imbalance.","whyItMatters":"Understanding the specific hormonal dysfunction in PWS could lead to targeted therapies for the uncontrollable hunger that is the hallmark of this genetic condition, which currently has no effective pharmacological treatment.","specificNumbers":"30 per group; 9 hormones; 4 time points; 23/27 PWS in Cluster 2; elevated ghrelin, leptin, PYY, GIP, GLP-1; PP declined post-60 min","methodology":"Prospective study comparing 30 PWS adults, 30 obese controls, and 30 healthy controls. Nine appetite-related peptides/hormones measured at fasting and 30, 60, and 120 minutes after a hypercaloric liquid diet. Cluster analysis applied.","limitations":"Moderate sample size (n=30 per group). Only 27 of 30 PWS patients had complete data for cluster analysis. Cross-sectional design cannot establish causation. Single meal challenge may not capture full hormonal dynamics."},{"rthcId":"RPEP-05295","title":"Can a Higher Protein/Low Glycemic Index vs. a Conventional Diet Attenuate Changes in Appetite and Gut Hormones Following Weight Loss? A 3-Year PREVIEW Sub-study.","authors":"Buso, Marion E C; Seimon, Radhika V; McClintock, Sally; Muirhead, Roslyn; Atkinson, Fiona S; Brodie, Shannon; Dodds, Jarron; Zibellini, Jessica; Das, Arpita; Wild-Taylor, Anthony L; Burk, Jessica; Fogelholm, Mikael; Raben, Anne; Brand-Miller, Jennie C; Sainsbury, Amanda","year":2021,"journal":"Frontiers in nutrition, 8, 640538","doi":"10.3389/fnut.2021.640538","pmid":"33829034","tags":["neuropeptides","weight-loss","hormone-optimization"],"studyType":"rct","evidenceStrength":"moderate","keyFinding":"Higher-protein, low-GI diet for weight maintenance did not attenuate post-weight-loss changes in ghrelin or PYY compared to moderate-protein diet, and appetite hormone changes did not predict weight regain over 3 years.","whyItMatters":"The idea that higher-protein diets could counter hormonal drivers of weight regain is popular but largely unproven. This well-designed long-term study provides important evidence that diet composition may not be sufficient to override the body's weight-regain physiology.","specificNumbers":"136 participants; 34-month follow-up; ~50% weight regain; ghrelin and PYY returned to baseline by 6-24 months","methodology":"Sub-study of the PREVIEW RCT. 136 adults with pre-diabetes underwent 2-month weight loss (≥8% body weight), then randomized to two dietary patterns for 34 months. Fasting ghrelin, PYY, and appetite sensations measured at 0, 2, 6, 12, 24, and 36 months.","limitations":"Sub-study of a larger trial with limited statistical power. Measured only total ghrelin and total PYY (not active forms). Self-reported dietary adherence. High attrition common in long-term diet studies."},{"rthcId":"RPEP-05296","title":"A GLP-1/GIP Dual Receptor Agonist DA4-JC Effectively Attenuates Cognitive Impairment and Pathology in the APP/PS1/Tau Model of Alzheimer's Disease.","authors":"Cai, Hong-Yan; Yang, Dan; Qiao, Jing; Yang, Jun-Ting; Wang, Zhao-Jun; Wu, Mei-Na; Qi, Jin-Shun; Hölscher, Christian","year":2021,"journal":"Journal of Alzheimer's disease : JAD, 83(2), 799-818","doi":"10.3233/JAD-210256","pmid":"34366339","tags":["glp-1","neuroprotection","cognitive-enhancement","research-status"],"studyType":"animal","evidenceStrength":"preliminary","keyFinding":"DA4-JC improved cognition, enhanced hippocampal synaptic function, normalized mitochondria via PINK1-Parkin pathway, and reduced both amyloid and p-tau pathology in APP/PS1/Tau transgenic mice.","whyItMatters":"Alzheimer's disease has no cure, and the diabetes-AD connection offers a promising therapeutic angle. Dual-agonist drugs targeting both GLP-1 and GIP receptors may be more effective than single-target approaches for neuroprotection.","specificNumbers":"Improved LTP; increased PSD95, synaptophysin; normalized PINK1-Parkin; reduced amyloid, p-tau, P62","methodology":"Preclinical study in triple-transgenic APP/PS1/Tau mice. Behavioral testing battery, in vivo hippocampal LTP recordings, Golgi staining for synapses, and biochemical analysis of AD biomarkers, synaptic proteins, and mitochondrial markers.","limitations":"Mouse model study — transgenic AD mice don't fully replicate human disease. Drug dosing, bioavailability, and blood-brain barrier penetration in humans remain unknown. No comparison with single-target GLP-1 agonists in this study."},{"rthcId":"RPEP-05297","title":"Derivatives of gecko cathelicidin-related antioxidant peptide facilitate skin wound healing.","authors":"Cai, Shasha; Lu, Changao; Liu, Zhenlei; Wang, Wenbo; Lu, Shuxin; Sun, Zhaoxing; Wang, Guannan","year":2021,"journal":"European journal of pharmacology, 890, 173649","doi":"10.1016/j.ejphar.2020.173649","pmid":"33049300","tags":["antimicrobial-peptides","ll-37","wound-healing","skin-repair","peptide-design"],"studyType":"animal","evidenceStrength":"preliminary","keyFinding":"Two short gecko cathelicidin-derived peptides (38-42 and 33-42 fragments) showed potent antioxidant and wound healing activity in mice with significantly lower toxicity than the parent peptide.","whyItMatters":"Chronic and slow-healing wounds affect millions of people. Antimicrobial peptides with wound-healing properties from natural sources offer potential new therapeutic options, especially as antibiotic resistance grows.","specificNumbers":"2 truncated peptides; strong ABTS/DPPH scavenging; increased SOD; decreased MDA; accelerated wound closure","methodology":"Peptide design and synthesis of Gj-CATH3 analogues, followed by in vitro antioxidant (ABTS, DPPH), cytotoxicity, and hemolysis assays, then in vivo full-thickness skin wound healing experiments in mice.","limitations":"Mouse wound model may not fully reflect human wound healing. Only two derivative peptides tested in vivo. Long-term safety and optimal dosing not established. Manufacturing scalability not addressed."},{"rthcId":"RPEP-05298","title":"ACE Inhibitory Peptide from Skin Collagen Hydrolysate of Takifugu bimaculatus as Potential for Protecting HUVECs Injury.","authors":"Cai, Shuilin; Pan, Nan; Xu, Min; Su, Yongchang; Qiao, Kun; Chen, Bei; Zheng, Bingde; Xiao, Meitian; Liu, Zhiyu","year":2021,"journal":"Marine drugs, 19(12)","doi":"10.3390/md19120655","pmid":"34940654","tags":["bioactive-food-peptides","collagen-peptides","cardiovascular","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"The collagen-derived peptide FNLRMQ inhibits ACE activity and protects blood vessel endothelial cells from angiotensin II-induced injury through Nrf2/HO-1 and PI3K/Akt/eNOS signaling pathways.","whyItMatters":"High blood pressure affects over a billion people worldwide. Natural ACE-inhibiting peptides from marine sources could provide alternatives to synthetic ACE inhibitor drugs with potentially fewer side effects.","specificNumbers":"Peptide FNLRMQ; ACE inhibition confirmed; Nrf2/HO-1 and PI3K/Akt/eNOS pathways activated","methodology":"Molecular docking to identify ACE-inhibitory peptides from pufferfish collagen hydrolysate, followed by in vitro testing on angiotensin II-induced HUVECs for cell viability, apoptosis, and signaling pathway analysis.","limitations":"In vitro study only using human cell lines. No animal or human trial data. Single peptide tested. Bioavailability and stability in the body not assessed."},{"rthcId":"RPEP-05299","title":"Effects of GLP-1 Receptor Agonists on Bone Mineral Density in Patients with Type 2 Diabetes Mellitus: A 52-Week Clinical Study.","authors":"Cai, Ting-Ting; Li, Hui-Qin; Jiang, Lan-Lan; Wang, Hui-Ying; Luo, Meng-Hui; Su, Xiao-Fei; Ma, Jian-Hua","year":2021,"journal":"BioMed research international, 2021, 3361309","doi":"10.1155/2021/3361309","pmid":"34580638","tags":["glp-1","exenatide","dulaglutide","bone-joint","diabetes"],"studyType":"rct","evidenceStrength":"moderate","keyFinding":"GLP-1 RAs increased bone mineral density at multiple skeletal sites over 52 weeks, while placebo showed significant bone loss at the spine, femoral neck, and total hip.","whyItMatters":"Diabetes increases fracture risk, and some diabetes drugs worsen bone health. Finding that GLP-1 RAs may actually improve bone density adds another reason to consider these drugs for patients with type 2 diabetes.","specificNumbers":"65 patients; 52 weeks; HbA1c 8.11→7.40 (exenatide), 8.77→7.06 (dulaglutide); BMD increased at L1-L4, femoral neck, total hip with GLP-1RAs","methodology":"Single-blinded RCT with 65 T2DM patients randomized to exenatide (n=19), dulaglutide (n=19), insulin glargine (n=10), or placebo (n=17) for 52 weeks. BMD measured by dual-energy X-ray absorptiometry (DXA).","limitations":"Small sample size (65 total, 10-19 per group). Single-blinded design. 52-week duration may not capture long-term effects. No fracture outcomes assessed."},{"rthcId":"RPEP-05300","title":"Potential anticarcinogenic effect of goat milk-derived bioactive peptides on HCT-116 human colorectal carcinoma cell line.","authors":"Cakir, Bilal; Tunali-Akbay, Tugba","year":2021,"journal":"Analytical biochemistry, 622, 114166","doi":"10.1016/j.ab.2021.114166","pmid":"33726980","tags":["bioactive-food-peptides","cancer"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Pepsin-treated goat milk casein fraction caused 80.92% apoptotic cell death in HCT-116 human colorectal cancer cells, the highest among all enzyme-protein combinations tested.","whyItMatters":"Colorectal cancer is the third most common cancer worldwide. Identifying food-derived peptides with anti-cancer properties could lead to novel preventive strategies or complementary treatments with fewer side effects than conventional chemotherapy.","specificNumbers":"80.92% apoptotic cell death; pepsin-treated casein most effective; 3 enzymes tested","methodology":"Goat milk casein and whey proteins digested with trypsin, pepsin, and papain. Peptides characterized by LC-QTOF-MS. Cytotoxicity assessed by MTT assay and cell death type analyzed by flow cytometry (Annexin V/PI) on HCT-116 cells.","limitations":"In vitro study using a single cancer cell line. No testing on normal cells for selectivity. No animal or human studies. Crude peptide fraction tested — specific active peptides not isolated. Concentrations used may not be achievable through dietary intake."},{"rthcId":"RPEP-05301","title":"Ghrelin Receptors Enhance Fat Taste Responsiveness in Female Mice.","authors":"Calder, Ashley N; Yu, Tian; Dahir, Naima S; Sun, Yuxiang; Gilbertson, Timothy A","year":2021,"journal":"Nutrients, 13(4)","doi":"10.3390/nu13041045","pmid":"33804920","tags":["ghrp","weight-loss","receptor-signaling"],"studyType":"animal","evidenceStrength":"preliminary","keyFinding":"Ghrelin receptors co-localize with Type II taste cells and their deletion reduces fat taste sensitivity specifically in female mice after high-fat diet exposure.","whyItMatters":"Understanding how appetite hormones influence taste perception could explain sex differences in food preferences and eating behaviors, potentially leading to targeted interventions for obesity.","specificNumbers":"GHS-R co-localized with PLCβ2; 6 weeks 60% HFD; female Ghsr-/- reduced LA response; no male effect","methodology":"Transgenic GHS-R-GFP mice for receptor localization via immunohistochemistry. Feeding studies and conditioned taste aversion assays comparing GHS-R knockout and wild-type mice on 60% high-fat diet for 6 weeks.","limitations":"Mouse study — taste perception mechanisms may differ in humans. Only fat taste tested; effects on other taste modalities not explored. Knockout model eliminates receptors entirely rather than mimicking physiological variation."},{"rthcId":"RPEP-05302","title":"The potential anti-inflammatory and anti-nociceptive effects of rat hemopressin (PVNFKFLSH) in experimental arthritis.","authors":"Camargo, Livia L; Denadai-Souza, Alexandre; Yshii, Lidia M; Lima, Carla; Teixeira, Simone A; Cerqueira, Anderson R A; Gewehr, Mayara C F; Fernandes, Elizabeth S; Schenka, André A; Muscará, Marcelo N; Ferro, Emer S; Costa, Soraia K P","year":2021,"journal":"European journal of pharmacology, 890, 173636","doi":"10.1016/j.ejphar.2020.173636","pmid":"33053380","tags":["neuropeptides","pain","inflammation","bone-joint"],"studyType":"animal","evidenceStrength":"preliminary","keyFinding":"Hemopressin reduced arthritis-induced joint swelling, pain behavior, and inflammatory markers (MPO, leukocytes, IL-6) via both intra-articular and oral routes, independent of CGRP and substance P.","whyItMatters":"Rheumatoid arthritis affects millions and current treatments have significant side effects. A peptide targeting the endocannabinoid system that works both locally and orally could offer a novel therapeutic approach with a different safety profile.","specificNumbers":"10-20 mcg/day i.art.; 20 mcg/kg oral; 4 days; reduced swelling, MPO, leukocytes, IL-6; SP and CGRP unchanged","methodology":"Antigen-induced arthritis (AIA) in rats via intra-articular mBSA injection. Treatments: Hp (10/20 μg i.art. or 20 μg/kg oral) daily for 4 days. Measures: joint edema, gait analysis, leukocyte counts, cytokines, and spinal cord neuropeptide immunoreactivity.","limitations":"Animal study — rat arthritis model may not fully represent human RA. Short 4-day treatment period. Small group sizes implied. Long-term safety and efficacy not assessed."},{"rthcId":"RPEP-05303","title":"Glucagon-Like Peptide 1 Receptor Agonist (GLP1RA) Exposure and Outcomes in Type 2 Diabetes: A Systematic Review of Population-Based Observational Studies.","authors":"Caparrotta, Thomas M; Templeton, Jack B; Clay, Thomas A; Wild, Sarah H; Reynolds, Rebecca M; Webb, David J; Colhoun, Helen M","year":2021,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 12(4), 969-989","doi":"10.1007/s13300-021-01021-1","pmid":"33635502","tags":["glp-1","exenatide","liraglutide","cardiovascular","peptide-safety","clinical-trials"],"studyType":"systematic-review","evidenceStrength":"strong","keyFinding":"Across 200,148 participants and 396,457 person-years, GLP-1 RAs showed cardiovascular safety with potential MACE benefit for liraglutide (PE range 0.53-0.95) and no association with pancreatitis, pancreatic cancer, breast cancer, or hypoglycemia.","whyItMatters":"Real-world evidence complements clinical trials by including broader patient populations and detecting rare safety signals. This comprehensive review provides reassurance about GLP-1 RA safety for both patients and prescribers.","specificNumbers":"22 studies; 200,148 participants; 396,457 person-years; liraglutide MACE 0.53-0.95; no increased pancreatitis, PC, BC, or hypoglycemia","methodology":"Pre-registered systematic review (PROSPERO CRD42020165720) following MOOSE guidelines. 22 population-based observational studies identified, covering mortality, CVD, pancreatitis, pancreatic cancer, thyroid cancer, renal failure, retinopathy, breast cancer, and hypoglycemia.","limitations":"Observational studies are subject to confounding and selection bias. Limited data on thyroid cancer, renal outcomes, and retinopathy (only one study each). Primarily data on exenatide and liraglutide — newer agents underrepresented."},{"rthcId":"RPEP-05304","title":"Lanreotide autogel/depot in advanced enteropancreatic neuroendocrine tumours: final results of the CLARINET open-label extension study.","authors":"Caplin, Martyn E; Pavel, Marianne; Phan, Alexandria T; Cwikla, Jaroslaw B; Sedlackova, Eva; Cadiot, Guillaume; Wolin, Edward M; Capdevila, Jaume; Wall, Lucy; Rindi, Guido; Langley, Alison; Martinez, Santiago; Ruszniewski, Philippe","year":2021,"journal":"Endocrine, 71(2), 502-513","doi":"10.1007/s12020-020-02475-2","pmid":"32844290","tags":["somatostatin-analogs"],"studyType":"human-rct-extension","evidenceStrength":"strong","keyFinding":"Long-term lanreotide: median PFS 32.8 months from OLE entry for continuous lanreotide patients. Placebo-to-lanreotide crossover patients had 14.0 months PFS.","whyItMatters":"Confirms sustained antiproliferative benefit of lanreotide beyond 96 weeks, supporting long-term use.","specificNumbers":"Median PFS 32.8 months (continuous); 14.0 months (crossover)","methodology":"Open-label extension of CLARINET phase 3 trial. All patients received lanreotide 120mg q28d.","limitations":"Open-label, no blinded comparison. Selection bias in extension enrollment."},{"rthcId":"RPEP-05305","title":"Agonist of growth hormone-releasing hormone enhances retinal ganglion cell protection induced by macrophages after optic nerve injury.","authors":"Cen, Ling-Ping; Ng, Tsz Kin; Liang, Jia-Jian; Xu, Ciyan; Zhuang, Xi; Liu, Yu-Fen; Chen, Shao-Lang; Xu, Yanxuan; Yang, Qichen; Yuan, Xiang-Ling; Qin, Yong Jie; Chan, Sun On; Chen, Haoyu; Zhang, Mingzhi; Schally, Andrew V; Pang, Chi Pui","year":2021,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 118(28)","doi":"10.1073/pnas.1920834118","pmid":"34244423","tags":["hormone-optimization","neuroprotection","eye-health","immune-function"],"studyType":"animal","evidenceStrength":"preliminary","keyFinding":"GHRH agonist MR-409 protected retinal ganglion cells after optic nerve injury and additively enhanced macrophage-mediated neuroprotection, with effects mediated through Akt phosphorylation and microglial activation.","whyItMatters":"Glaucoma affects over 100 million people worldwide with no cure. Finding that GHRH agonists can protect retinal nerve cells and enhance existing neuroprotective mechanisms opens a new therapeutic avenue for preserving vision.","specificNumbers":"GHRH-R on RGCs confirmed; MR-409 increased RGC survival; Akt phosphorylation increased; microglia activated by agonist; IL-1β, IL-6, TNF reduced by antagonist","methodology":"Rat optic nerve crush model. Subcutaneous GHRH agonist (MR-409) or antagonist (MIA-602) treatment. RGC survival quantification, retinal Akt phosphorylation, microglial activation, inflammation gene expression, and combination with lens injury/zymosan-induced macrophage activation.","limitations":"Rat model — optic nerve crush differs from the gradual nerve damage in human glaucoma. Subcutaneous administration raises questions about achieving sufficient drug levels in the eye. Long-term effects not studied."},{"rthcId":"RPEP-05306","title":"AP Collagen Peptides Prevent Cortisol-Induced Decrease of Collagen Type I in Human Dermal Fibroblasts.","authors":"Chae, Minjung; Bae, Il-Hong; Lim, Sung Hwan; Jung, Kyoungmi; Roh, Jonghwa; Kim, Wangi","year":2021,"journal":"International journal of molecular sciences, 22(9)","doi":"10.3390/ijms22094788","pmid":"33946465","tags":["collagen-peptides","skin-repair","bioactive-food-peptides"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"AP collagen peptides blocked cortisol-induced GR activation and prevented the suppression of TGF-β signaling and collagen type I production in human dermal fibroblasts, senescent cells, and skin models.","whyItMatters":"Chronic stress visibly ages skin partly through cortisol-mediated collagen breakdown. Finding that oral collagen peptides can mechanistically block this pathway provides scientific backing for collagen supplements' skin health claims.","specificNumbers":"3% GPH content; GR blocked; TGF-β restored; collagen I recovered; validated in senescent cells and 3D skin model","methodology":"In vitro study using human dermal fibroblasts (HDFs), senescent HDFs, and reconstituted human skin models. Cortisol treatment with/without AP collagen peptides or GR inhibitors. Measured collagen type I expression, GR activation, and TGF-β signaling.","limitations":"In vitro study — uncertain whether oral collagen peptides reach the skin at sufficient concentrations to produce these effects in vivo. Used a specific commercial peptide preparation. No clinical trial data."},{"rthcId":"RPEP-05307","title":"Characterization and functional analysis of cathelicidin-MH, a novel frog-derived peptide with anti-septicemic properties.","authors":"Chai, Jinwei; Chen, Xin; Ye, Tiaofei; Zeng, Baishuang; Zeng, Qingye; Wu, Jiena; Kascakova, Barbora; Martins, Larissa Almeida; Prudnikova, Tatyana; Smatanova, Ivana Kuta; Kotsyfakis, Michail; Xu, Xueqing","year":2021,"journal":"eLife, 10","doi":"10.7554/eLife.64411","pmid":"33875135","tags":["antimicrobial-peptides","ll-37","infection","inflammation"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"Cathelicidin-MH protected mice from lethal sepsis through a unique combination of antimicrobial activity, LPS neutralization, coagulation suppression (affecting tPA, plasmin, tryptase, elastase, thrombin, and chymase), and MAPK signaling inhibition.","whyItMatters":"Sepsis kills more than 11 million people annually and current treatments are limited. A peptide that simultaneously fights infection, neutralizes endotoxin, and controls coagulation addresses multiple sepsis mechanisms at once.","specificNumbers":"Active vs Gram-negatives and fungi; 6 coagulation enzymes inhibited; 2 sepsis models; reduced cytokines; blocked MAPK","methodology":"Peptide isolation and structural characterization. In vitro antimicrobial and coagulation assays. In vivo LPS-induced and cecal ligation/puncture sepsis models in mice. Organ pathology, inflammatory cytokine, and signaling pathway analysis.","limitations":"Mouse sepsis models don't perfectly predict human sepsis outcomes. Peptide stability, pharmacokinetics, and manufacturing costs not addressed. Published in eLife (high-quality journal) but still preclinical."},{"rthcId":"RPEP-05308","title":"Antimicrobial Activity of the Peptide LfcinB15 against Candida albicans.","authors":"Chang, Che-Kang; Kao, Mou-Chieh; Lan, Chung-Yu","year":2021,"journal":"Journal of fungi (Basel, Switzerland), 7(7)","doi":"10.3390/jof7070519","pmid":"34209722","tags":["antimicrobial-peptides","infection","bioactive-food-peptides"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"LfcinB15 kills Candida albicans through at least three mechanisms: membrane disruption, ROS generation, and mitochondrial dysfunction, while activating Hog1 and Mkc1 stress-response kinases.","whyItMatters":"Candida infections are increasingly resistant to conventional antifungal drugs. Understanding how antimicrobial peptides kill fungi through multiple simultaneous mechanisms could help develop new antifungal strategies that are harder for pathogens to resist.","specificNumbers":"Active vs planktonic + biofilm C. albicans + clinical isolates + non-albicans; membrane disruption; ROS generation; mitochondrial dysfunction; Hog1 + Mkc1 activated","methodology":"In vitro susceptibility testing against planktonic and biofilm cells. Fluorescence microscopy for peptide localization. Membrane integrity assays, ROS detection, mitochondrial function assessment, and Western blot for MAPK activation in C. albicans.","limitations":"In vitro study only. No animal infection model data. Peptide stability and efficacy in vivo not tested. Specific MIC values not reported in abstract."},{"rthcId":"RPEP-05309","title":"Doping control analysis of small peptides in human urine using LC-HRMS with parallel reaction monitoring mode: screening and confirmation.","authors":"Chang, Wei; He, Genye; Yan, Kuan; Wang, Zhanliang; Zhang, Yufeng; Dong, Tianyu; Liu, Yunxi; Zhang, Lisi; Hong, Liu","year":2021,"journal":"Analytical methods : advancing methods and applications, 13(48), 5838-5850","doi":"10.1039/d1ay01677f","pmid":"34847571","tags":["anti-doping","detection-methods","peptide-analysis"],"studyType":"Method Validation Study","evidenceStrength":"Strong","keyFinding":"Researchers developed and validated a method using liquid chromatography with high-resolution mass spectrometry (LC-HRMS) in parallel reaction monitoring (PRM) mode to detect 41 small peptides and 3 non-peptide growth hormone secretagogues in human urine. The method achieved detection limits between 0.20 and 0.92 ng/mL, meeting all WADA minimum performance requirements.\n\nThe technique was validated on over 5,000 real urine samples with zero false positives and zero false negatives. The entire chromatographic run takes just 14 minutes, making it efficient for high-throughput anti-doping laboratories. The PRM mode dramatically reduces background noise from the urine matrix, improving both the reliability of screening and the accuracy of confirmation testing.","whyItMatters":"Peptide doping — using substances like growth hormone-releasing peptides, GnRH analogs, and other small peptides to enhance performance — is a growing concern in competitive sports. Detecting these substances in urine is technically challenging because peptides are present at very low concentrations and can be masked by the complex biological matrix. This validated method gives anti-doping labs a fast, reliable tool to catch peptide use, covering 44 prohibited substances in a single 14-minute run.","specificNumbers":"41 small peptides + 3 non-peptide GH secretagogues · LOD 0.20–0.92 ng/mL · LOI 0.20–2.00 ng/mL · 14-min runtime · 5,000+ samples validated · 0 false positives · 0 false negatives","methodology":"The researchers combined solid-phase extraction (SPE) sample preparation with LC-HRMS detection using parallel reaction monitoring (PRM) mode. They validated the method according to WADA criteria, testing selectivity, reliability, limits of detection and identification, recovery rates, extraction stability, and carryover. The method was then applied to over 5,000 real urine samples from doping control to verify real-world performance.","limitations":"The method focuses on small peptides and may not cover larger peptide hormones that require different analytical approaches. Detection limits, while meeting WADA requirements, vary across the 44 analytes. The study does not address how microdosing strategies or timing of peptide use might affect detection windows. Real-world applicability may also depend on individual lab equipment and operator expertise."},{"rthcId":"RPEP-05310","title":"Research on Correlation Between Psychological Factors, Mast Cells, and PAR-2 Signal Pathway in Irritable Bowel syndrome.","authors":"Chao, Guanqun; Wang, Zhaojun; Zhang, Shuo","year":2021,"journal":"Journal of inflammation research, 14, 1427-1436","doi":"10.2147/JIR.S300513","pmid":"33883919","tags":["neuropeptides","gut-healing","inflammation","anxiety-mood"],"studyType":"observational","evidenceStrength":"preliminary","keyFinding":"IBS-D patients showed downregulated NPS, NPY, and NPY2R alongside increased mast cell activation and PAR-2 expression, suggesting mast cell-driven neuropeptide changes link gut inflammation to psychological symptoms.","whyItMatters":"IBS affects up to 15% of the global population. Understanding the molecular connection between stress, neuropeptides, and gut symptoms could lead to targeted therapies addressing both the psychological and gastrointestinal components simultaneously.","specificNumbers":"28 IBS-D vs 8 controls; MC and tryptase-positive MC increased; PAR-2 up; NPS, NPY, NPY2R down; SDS and SAS scores higher in IBS","methodology":"Case-control study: 28 IBS-D patients vs. 8 healthy controls. Colonoscopic biopsies analyzed by immunohistochemistry and Western blot. ELISA for NPS and NPY in plasma and tissue. SDS and SAS for psychological assessment.","limitations":"Small sample size, especially controls (n=8). Cross-sectional design cannot establish causation. IBS-D subtype only — may not apply to constipation-predominant IBS. Correlation between indicators doesn't prove the proposed causal pathway."},{"rthcId":"RPEP-05311","title":"Peptide-Based Vaccines for Hepatocellular Carcinoma: A Review of Recent Advances.","authors":"Charneau, Jimmy; Suzuki, Toshihiro; Shimomura, Manami; Fujinami, Norihiro; Nakatsura, Tetsuya","year":2021,"journal":"Journal of hepatocellular carcinoma, 8, 1035-1054","doi":"10.2147/JHC.S291558","pmid":"34513746","tags":["cancer","immune-function","clinical-trials"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Peptide vaccines targeting GPC3 have shown safety and immune activation in HCC clinical trials, and neoantigen vaccines represent a promising next step with preclinical data supporting clinical trial initiation.","whyItMatters":"Liver cancer has high recurrence rates (up to 70% after surgery) and limited treatment options. Peptide vaccines could help prevent recurrence and treat advanced disease by training the immune system to attack cancer cells.","specificNumbers":"HCC 6th most common cancer; 70% relapse after surgery; GPC3, WT-1, AFP, ROBO1, FOXM1 targets; Phase I/II trials","methodology":"Review of Phase I/II clinical trials of peptide vaccines in HCC, discussion of candidate tumor antigens, and presentation of preclinical neoantigen vaccine data.","limitations":"Review of early-phase trials with small patient numbers. Neoantigen data is preclinical only. Peptide vaccines alone have historically shown modest clinical responses in solid tumors."},{"rthcId":"RPEP-05312","title":"Oxytocin signaling in the treatment of drug addiction: Therapeutic opportunities and challenges.","authors":"Che, Xiaohang; Cai, Jialing; Liu, Yueyang; Xu, Tianyu; Yang, Jingyu; Wu, Chunfu","year":2021,"journal":"Pharmacology & therapeutics, 223, 107820","doi":"10.1016/j.pharmthera.2021.107820","pmid":"33600854","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Oxytocin administration can ameliorate a wide range of drug-induced neurobehavioral changes across all three stages of addiction: it suppresses drug reward during the binge stage, reduces stress responses and social impairments during withdrawal, and prevents drug-, cue-, and stress-induced reinstatement. Clinical studies have shown beneficial effects of oxytocin on reducing substance use disorders involving heroin, cocaine, alcohol, cannabis, and nicotine.","whyItMatters":"Drug addiction remains one of the leading causes of death worldwide, and current treatments have poor effectiveness with serious side effects. Oxytocin represents a fundamentally different approach — a naturally occurring neuropeptide that targets the social and stress circuits hijacked by addiction, rather than simply blocking drug receptors.","specificNumbers":"","methodology":"This was a comprehensive narrative review of both preclinical (animal) and clinical (human) studies examining oxytocin's role in treating drug addiction. The authors synthesized evidence on how drugs of abuse affect the oxytocin system and how oxytocin administration modifies addictive behaviors, covering neurobiological mechanisms and therapeutic potential of oxytocin and its analogs.","limitations":"As a review article, this study did not generate new experimental data. Many of the findings it synthesizes come from animal models, which may not fully translate to humans. The clinical evidence, while promising, involves relatively small human studies. The review also acknowledges that oxytocin's poor blood-brain barrier penetration and short half-life remain practical challenges for therapeutic use."},{"rthcId":"RPEP-05313","title":"Challenges targeting cancer neoantigens in 2021: a systematic literature review.","authors":"Chen, Ina; Chen, Michael Y; Goedegebuure, S Peter; Gillanders, William E","year":2021,"journal":"Expert review of vaccines, 20(7), 827-837","doi":"10.1080/14760584.2021.1935248","pmid":"34047245","tags":["cancer","immune-function","peptide-design"],"studyType":"systematic-review","evidenceStrength":"moderate","keyFinding":"Current neoantigen prediction pipelines have significant limitations in accuracy, while tumor heterogeneity and immunosuppressive microenvironments remain major barriers to successful cancer neoantigen vaccine translation.","whyItMatters":"Personalized cancer vaccines could theoretically treat any cancer type by targeting its unique mutations. Understanding current limitations is essential for directing research efforts toward solutions.","specificNumbers":"2 identification strategies; challenges: prediction accuracy, tumor heterogeneity, immunosuppression; ML improving rapidly","methodology":"Systematic literature review covering neoantigen identification strategies, prediction pipeline limitations, and challenges in clinical translation of cancer neoantigen vaccines.","limitations":"Review article that summarizes existing literature without generating new data. The field is moving rapidly, so some information may become outdated quickly."},{"rthcId":"RPEP-05314","title":"Molecular characterization of cathelicidin in tiger frog (Hoplobatrachus rugulosus): Antimicrobial activity and immunomodulatory activity.","authors":"Chen, Jie; Lin, You-Fu; Chen, Jia-Hao; Chen, Xiang; Lin, Zhi-Hua","year":2021,"journal":"Comparative biochemistry and physiology. Toxicology & pharmacology : CBP, 247, 109072","doi":"10.1016/j.cbpc.2021.109072","pmid":"33965586","tags":["antimicrobial-peptides","ll-37","immune-function","infection"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Tiger frog cathelicidin HR-CATH combines direct antimicrobial activity (membrane disruption, DNA degradation) with immune-stimulating properties (macrophage chemotaxis and respiratory burst enhancement).","whyItMatters":"Antimicrobial peptides that both kill pathogens and boost immune responses are especially valuable as antibiotic alternatives, since they attack infections through multiple mechanisms that are harder for bacteria to resist.","specificNumbers":"Active vs V. parahaemolyticus, S. aureus, A. hydrophila; LDH release confirmed membrane damage; dose-dependent DNA degradation; chemotaxis and respiratory burst in macrophages","methodology":"cDNA cloning from skin transcriptome, chemical synthesis, in vitro antimicrobial testing, membrane integrity assays, DNA degradation assays, and immunomodulation testing in RAW264.7 macrophage cells.","limitations":"In vitro study only. No animal infection model tested. Peptide stability in vivo and therapeutic index not assessed. Limited to three bacterial species tested."},{"rthcId":"RPEP-05315","title":"Parathyroid hormone and its related peptides in bone metabolism.","authors":"Chen, Tianhong; Wang, Yi; Hao, Zhuowen; Hu, Yingkun; Li, Jingfeng","year":2021,"journal":"Biochemical pharmacology, 192, 114669","doi":"10.1016/j.bcp.2021.114669","pmid":"34224692","tags":["bone-joint","hormone-optimization","receptor-signaling","dosing"],"studyType":"review","evidenceStrength":"strong","keyFinding":"PTH's dual bone-building and bone-resorbing effects depend on administration pattern, working through Wnt, cAMP, and RANKL pathways. PTH-related peptides in development may overcome teriparatide's clinical limitations.","whyItMatters":"Osteoporosis affects hundreds of millions worldwide. Understanding how PTH peptides control bone building and breakdown is essential for developing better treatments that maximize bone formation while minimizing bone loss.","specificNumbers":"84-aa hormone; PTH(1-34) teriparatide; Wnt, cAMP/PKA, cAMP/PKC, RANKL/RANK/OPG pathways; intermittent = anabolic, continuous = catabolic","methodology":"Comprehensive review of published literature on PTH and PTH-related peptide mechanisms in bone metabolism.","limitations":"Review article synthesizing existing literature. Does not include new experimental data. PTH-related peptides discussed may still be in early development stages."},{"rthcId":"RPEP-05316","title":"cAMP signaling through protein kinase A and Epac2 induces substance P release in the rat spinal cord.","authors":"Chen, Wenling; McRoberts, James A; Ennes, Helena S; Marvizon, Juan Carlos","year":2021,"journal":"Neuropharmacology, 189, 108533","doi":"10.1016/j.neuropharm.2021.108533","pmid":"33744339","tags":["neuropeptides","pain","receptor-signaling"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"cAMP drives substance P release through dual PKA and Epac2 pathways, but Epac2's contribution is selectively lost during latent pain sensitization, potentially reflecting chronic pain-related neural remodeling.","whyItMatters":"Understanding the specific signaling cascades that control substance P release could identify new therapeutic targets for chronic pain that are more selective than broadly acting painkillers.","specificNumbers":"PKA phosphorylates NR1 + NR2B; Epac2 via Raf-MAPK; TRPV1/TRPA1 not involved; Epac2 effect lost in latent sensitization","methodology":"Rat spinal cord slice preparations with NK1R internalization as a measure of substance P release. Pharmacological manipulation with cAMP analogs, pathway inhibitors, and NMDA antagonists. Calcium imaging in cultured dorsal horn neurons. Latent sensitization pain model.","limitations":"Rat spinal cord slice preparations may not fully reflect in vivo pain processing. Pharmacological tools may have off-target effects. Latent sensitization model is one specific chronic pain paradigm."},{"rthcId":"RPEP-05317","title":"A Neoantigen-Based Peptide Vaccine for Patients With Advanced Pancreatic Cancer Refractory to Standard Treatment.","authors":"Chen, Zheling; Zhang, Shanshan; Han, Ning; Jiang, Jiahong; Xu, Yunyun; Ma, Dongying; Lu, Lantian; Guo, Xiaojie; Qiu, Min; Huang, Qinxue; Wang, Huimin; Mo, Fan; Chen, Shuqing; Yang, Liu","year":2021,"journal":"Frontiers in immunology, 12, 691605","doi":"10.3389/fimmu.2021.691605","pmid":"34484187","tags":["cancer","immune-function","clinical-trials"],"studyType":"case-series","evidenceStrength":"preliminary","keyFinding":"Personalized neoantigen vaccine was safe in pancreatic cancer with low tumor mutation burden; one patient showed dramatic antigen-specific T-cell expansion from 0% to ~100% with 21-month vaccine-associated survival.","whyItMatters":"Pancreatic cancer has a 5-year survival rate under 10% and limited treatment options. This is among the first studies showing personalized neoantigen vaccines can work even in cancers with low mutation burden.","specificNumbers":"7 patients; up to 20 peptides each; TMB <10; OS 24.1 mo; vaccine OS 8.3 mo; PFS 3.1 mo; P01: 21 mo, TCR 0→~100%","methodology":"Retrospective study of 7 advanced pancreatic cancer patients. Up to 20 neoantigen peptides per patient identified by iNeo-Suite pipeline. Multiple vaccine doses administered. Immune monitoring via ELISpot and flow cytometry pre/post-vaccination.","limitations":"Very small sample (n=7). Retrospective design. No control group. Heterogeneous patient population. Cannot definitively attribute survival to vaccine therapy."},{"rthcId":"RPEP-05318","title":"Substance P restores spermatogenesis in busulfan-treated mice: A new strategy for male infertility therapy.","authors":"Chen, Zhihong; Liu, Minjie; Hu, Jin-Hua; Gao, Yong; Deng, Chunhua; Jiang, Mei Hua","year":2021,"journal":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 133, 110868","doi":"10.1016/j.biopha.2020.110868","pmid":"33181455","tags":["neuropeptides","fertility"],"studyType":"animal","evidenceStrength":"preliminary","keyFinding":"Substance P at 5 nmol/kg restored spermatogenesis in busulfan-treated azoospermic mice by stimulating spermatogonia proliferation via NK1R-ERK1/2 signaling.","whyItMatters":"Male infertility due to chemotherapy is a growing concern as cancer survival improves. Finding that a known neuropeptide can restore sperm production opens a potential new therapeutic approach for chemotherapy-induced infertility.","specificNumbers":"5 nmol/kg SP; increased ZBTB16+, LIN28+, STRA8+ spermatogonia; 100 nM SP stimulated proliferation via ERK1/2; RP67580 blocked effect","methodology":"Busulfan-induced non-obstructive azoospermia mouse model. SP treatment (5 nmol/kg). In vitro seminiferous tubule culture and GC-1 spg cell line proliferation assays. NK-1R antagonist (RP67580) studies. Spermatogonia markers: ZBTB16+, LIN28+, STRA8+.","limitations":"Mouse model — may not directly translate to humans. Busulfan-induced azoospermia is one specific cause of infertility. Long-term effects and offspring health not assessed. Small study implied by model system."},{"rthcId":"RPEP-05319","title":"Cardiorenal mechanisms of action of glucagon-like-peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors.","authors":"Cherney, David Z I; Udell, Jacob A; Drucker, Daniel J","year":2021,"journal":"Med (New York, N.Y.), 2(11), 1203-1230","doi":"10.1016/j.medj.2021.10.004","pmid":"35590197","tags":["glp-1","cardiovascular","kidney","diabetes"],"studyType":"review","evidenceStrength":"strong","keyFinding":"GLP-1 RAs and SGLT2i protect cardiovascular and renal systems through distinct but complementary mechanisms: GLP-1 RAs reduce atherosclerotic events while SGLT2i reduce heart failure and preserve kidney function.","whyItMatters":"These drugs have transformed diabetes care by offering organ protection beyond blood sugar control. Understanding their mechanisms helps optimize treatment selection and supports their expansion to non-diabetic patients with cardiovascular or kidney disease.","specificNumbers":"GLP-1RA: reduced MACE, MI, stroke; SGLT2i: reduced HF, preserved eGFR; low cardiac receptor expression; mortality reduced","methodology":"Comprehensive mechanistic review of cardiovascular and renal outcome trial data with analysis of molecular mechanisms of GLP-1 RAs and SGLT2 inhibitors.","limitations":"Review limited to mechanisms known at time of publication. Exact mechanisms remain incompletely understood. Head-to-head comparisons between the two classes are limited."},{"rthcId":"RPEP-05320","title":"Inhibition of angiotensin converting enzyme induces mechanical allodynia through increasing substance P expression in mice.","authors":"Choi, Jae-Gyun; Choi, Sheu-Ran; Kang, Dong-Wook; Kim, Jaehyuk; Park, Jin Bong; Kim, Hyun-Woo","year":2021,"journal":"Neurochemistry international, 146, 105020","doi":"10.1016/j.neuint.2021.105020","pmid":"33744374","tags":["neuropeptides","pain","cardiovascular"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"ACE inhibitors increase substance P levels in spinal cord and DRG, causing mechanical allodynia through NK-1R signaling. ACE normally degrades substance P, revealing a previously underappreciated pain-related side effect mechanism.","whyItMatters":"ACE inhibitors are among the most prescribed drugs worldwide. Understanding that they can cause pain sensitivity through substance P accumulation may explain unexplained pain complaints in patients taking these medications.","specificNumbers":"10-day treatment; increased SP in DRG + spinal dorsal horn; allodynia reversed by L-733,060; intraplantar SP for 3 days caused allodynia; exogenous ACE blocked SP effect","methodology":"Mouse model with 10-day captopril or enalapril treatment (IP or intrathecal). Paw withdrawal frequency to mechanical stimuli. Substance P immunohistochemistry in lumbar DRG and spinal dorsal horn. NK-1R antagonist (L-733,060) rescue. Exogenous ACE and SP injection experiments.","limitations":"Mouse study — may not directly translate to human pain experiences. 10-day treatment may not reflect chronic clinical use. Only mechanical allodynia tested, not other pain types."},{"rthcId":"RPEP-05321","title":"Substance P Serves as a Balanced Agonist for MRGPRX2 and a Single Tyrosine Residue Is Required for β-Arrestin Recruitment and Receptor Internalization.","authors":"Chompunud Na Ayudhya, Chalatip; Amponnawarat, Aetas; Ali, Hydar","year":2021,"journal":"International journal of molecular sciences, 22(10)","doi":"10.3390/ijms22105318","pmid":"34070125","tags":["neuropeptides","immune-function","receptor-signaling"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Substance P serves as a balanced agonist for MRGPRX2, activating both G-protein and β-arrestin pathways. Tyr279 in the NPxxY motif is essential for both signaling modes.","whyItMatters":"MRGPRX2 is a key mediator of drug-induced pseudo-allergic reactions, neurogenic inflammation, and itch. Understanding how substance P activates this receptor could lead to better treatments for inflammatory skin conditions and drug reactions.","specificNumbers":"2 pathways: G protein + beta-arrestin; Y279A blocks beta-arrestin and internalization; balanced agonism by SP","methodology":"Cell-based assays measuring G-protein signaling, β-arrestin recruitment, MRGPRX2 internalization, and desensitization. Site-directed mutagenesis (Y279A). G-protein independence verified with G-protein inhibitors.","limitations":"Cell-based overexpression system may not fully reflect native receptor behavior. Focused on one agonist (substance P); other MRGPRX2 agonists may have different signaling profiles."},{"rthcId":"RPEP-05322","title":"Human β-Defensin 2 and Its Postulated Role in Modulation of the Immune Response.","authors":"Cieślik, Martyna; Bagińska, Natalia; Górski, Andrzej; Jończyk-Matysiak, Ewa","year":2021,"journal":"Cells, 10(11)","doi":"10.3390/cells10112991","pmid":"34831214","tags":["antimicrobial-peptides","immune-function","infection","inflammation","gut-healing"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"hBD-2 acts as a broad-spectrum antimicrobial, immune modulator, and potential inflammation biomarker, with special importance in infant immunity and potential therapeutic use in inflammatory diseases and microbiome maintenance.","whyItMatters":"As antibiotic resistance grows and immune-mediated diseases increase, understanding natural antimicrobial peptides like hBD-2 that can both fight pathogens and regulate immunity is crucial for developing next-generation therapeutics.","specificNumbers":"Active vs bacteria, viruses, fungi, parasites; important in infants; inflammation marker; microbiota balance","methodology":"Review of published literature on hBD-2 structure, function, and therapeutic potential.","limitations":"Review article without new experimental data. Some therapeutic claims are based on limited evidence. Translation from basic research to clinical application remains challenging."},{"rthcId":"RPEP-05323","title":"Immunogenicity of biologic therapies for migraine: a review of current evidence.","authors":"Cohen, Joshua M; Ning, Xiaoping; Kessler, Yoel; Rasamoelisolo, Michele; Campos, Verena Ramirez; Seminerio, Michael J; Krasenbaum, Lynda J; Shen, Honglue; Stratton, Jennifer","year":2021,"journal":"The journal of headache and pain, 22(1), 3","doi":"10.1186/s10194-020-01211-5","pmid":"33413094","tags":["neuropeptides","pain","peptide-safety","side-effects"],"studyType":"review","evidenceStrength":"strong","keyFinding":"ADA prevalence ranged from <1% to ~18% and neutralizing ADA from 0-12% across CGRP mAbs, with adverse events related to ADA formation rare across all four approved migraine antibodies.","whyItMatters":"Patients and clinicians considering long-term CGRP antibody therapy need to know whether the body will mount an immune reaction that could reduce drug effectiveness or cause side effects.","specificNumbers":"20 studies; 4 CGRP mAbs; ADA <1-18%; neutralizing 0-12%; adverse events rare","methodology":"Review of immunogenicity data from 20 studies (5 per antibody) including Phase 2, Phase 3, and long-term extension studies of eptinezumab, erenumab, fremanezumab, and galcanezumab.","limitations":"Direct cross-study comparison is impossible due to lack of standardized immunogenicity assays. Long-term data (beyond trial durations) is limited. Individual patient risk factors for ADA development are not well characterized."},{"rthcId":"RPEP-05324","title":"MRGPRX2 sensing of cationic compounds-A bridge between nociception and skin diseases?","authors":"Corbière, Auriane; Loste, Alexia; Gaudenzio, Nicolas","year":2021,"journal":"Experimental dermatology, 30(2), 193-200","doi":"10.1111/exd.14222","pmid":"33107136","tags":["neuropeptides","antimicrobial-peptides","pain","inflammation","skin-repair"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"MRGPRX2 acts as a broad sensor for cationic molecules, enabling mast cells to bridge nociception and skin inflammation, contributing to pruritus, pain, atopic dermatitis, and drug-induced reactions.","whyItMatters":"Understanding how mast cells connect nerve signaling to skin inflammation could lead to new treatments for itch, inflammatory skin diseases, and drug-induced reactions that target a single receptor rather than multiple downstream pathways.","specificNumbers":"Agonists: substance P, LL-37, venom peptides, QS molecules, FDA drugs; outputs: proteases, lipids, cytokines; targets: itch, pain, dermatitis, injection reactions","methodology":"Review of published literature on MRGPRX2/MRGPRB2 activation, signaling, and roles in skin diseases and nociception.","limitations":"Review article based on largely preclinical evidence. Mouse MRGPRB2 and human MRGPRX2 may differ in important ways. Clinical validation of MRGPRX2 as a therapeutic target is still needed."},{"rthcId":"RPEP-05325","title":"NK1 antagonists attenuate tau phosphorylation after blast and repeated concussive injury.","authors":"Corrigan, Frances; Cernak, Ibolja; McAteer, Kelly; Hellewell, Sarah C; Rosenfeld, Jeffrey V; Turner, Renée J; Vink, Robert","year":2021,"journal":"Scientific reports, 11(1), 8861","doi":"10.1038/s41598-021-88237-0","pmid":"33893374","tags":["neuropeptides","neuroprotection","pain","receptor-signaling"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"NK1 receptor antagonists attenuated tau hyperphosphorylation after blast and concussive TBI by modulating Akt, ERK1/2, and JNK kinases, with the mechanism initiated by TRPV1 mechanoreceptor-mediated substance P release.","whyItMatters":"CTE is a devastating neurodegenerative disease affecting athletes and military personnel with no prevention or treatment. Identifying that substance P mediates the initial tau pathology opens a potentially practicable therapeutic window for preventing CTE after known head injuries.","specificNumbers":"3 TBI models; NK1 antagonist reduced p-tau; modulated Akt, ERK1/2, JNK; TRPV1 inhibitor effective pre-injury only","methodology":"Mouse models of single moderate TBI, repeated concussive TBI, and blast-induced mild TBI. Post-injury NK1 antagonist or pre-injury TRPV1 inhibitor treatment. Tau phosphorylation analysis, kinase activity assessment, and neurological outcome testing.","limitations":"Mouse study — TBI models may not perfectly replicate human concussions or blast exposure. Post-injury treatment timing and duration for optimal effect not fully established. Long-term CTE prevention not demonstrated (only acute tau phosphorylation)."},{"rthcId":"RPEP-05326","title":"Differences between adult and adolescent male mice in approach/avoidance and expression of hippocampal NPY in response to acute footshock.","authors":"Cortes, Mariana A; Corder, Katelynn M; Dobrunz, Lynn E","year":2021,"journal":"Stress (Amsterdam, Netherlands), 24(6), 965-977","doi":"10.1080/10253890.2021.1976139","pmid":"34546150","tags":["neuropeptides","anxiety-mood","neuroprotection"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"After footshock stress, adolescent mice showed elevated hippocampal NPY and no anxiety increase, while adult mice showed reduced hippocampal NPY and increased anxiety — opposite neuropeptide responses to the same stressor.","whyItMatters":"Understanding why adolescent brains may be more resilient to acute stress could help develop age-appropriate treatments for anxiety and PTSD, particularly the role of NPY as a natural stress-protective factor.","specificNumbers":"30-min footshock; adults: reduced EPM open arm time + reduced hippocampal NPY; adolescents: no anxiety change + elevated hippocampal NPY; both: hypolocomotion","methodology":"Unpredictable footshock (30 min) in adolescent (6-week) and adult (3-month) male C57Bl6/J mice. Plasma corticosterone and NPY at baseline and post-shock. Elevated plus maze and open field 1 week later. Hippocampal NPY peptide expression by immunohistochemistry.","limitations":"Male mice only — sex differences in stress response are well-documented. Single stressor type (footshock). One-week post-stress timepoint may not capture long-term trajectories. Mouse adolescence may not perfectly model human adolescence."},{"rthcId":"RPEP-05327","title":"Multi-Epitope-Based Vaccines for Colon Cancer Treatment and Prevention.","authors":"Corulli, Lauren R; Cecil, Denise L; Gad, Ekram; Koehnlein, Marlese; Coveler, Andrew L; Childs, Jennifer S; Lubet, Ronald A; Disis, Mary L","year":2021,"journal":"Frontiers in immunology, 12, 729809","doi":"10.3389/fimmu.2021.729809","pmid":"34526999","tags":["cancer","immune-function"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"CDC25B and COX2 peptide vaccines consistently prevented colon cancer across three mouse models: transplanted tumor, AOM-induced, and APC Min genetic models, with 50% tumor-free rates in the AOM prevention setting.","whyItMatters":"Colorectal cancer is the third most common cancer worldwide. A preventive vaccine could dramatically reduce disease burden, especially for high-risk individuals with family history or genetic predisposition.","specificNumbers":"CDC25B + COX2 effective; 50% tumor-free (AOM); MC38 inhibited (p<0.0001); APC Min fewer tumors (CDC25B p=0.01, COX2 p=0.02); RCAS1 and FASCIN1 ineffective","methodology":"ELISA for serum antibodies in cancer patients. Human T-cell epitope prediction and validation by ELISPOT. Mouse immunization with homologous peptides. Three tumor models: MC38 syngeneic tumor challenge, AOM chemical carcinogen, and APC Min transgenic mice.","limitations":"Mouse study — immune responses and tumor biology differ from humans. Homologous but not identical peptides between mouse and human. RCAS1 vaccination showed no anti-tumor effect despite immunogenicity. Long-term prevention not assessed."},{"rthcId":"RPEP-05328","title":"Therapeutic Potential of Peptides Derived from Animal Venoms: Current Views and Emerging Drugs for Diabetes.","authors":"Coulter-Parkhill, Aimee; McClean, Stephen; Gault, Victor A; Irwin, Nigel","year":2021,"journal":"Clinical medicine insights. Endocrinology and diabetes, 14, 11795514211006071","doi":"10.1177/11795514211006071","pmid":"34621137","tags":["venom-peptides","glp-1","exenatide","diabetes"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Venom-derived peptides from diverse species (bees, cone snails, sea anemones, scorpions, snakes, spiders) show potential for glycemic control, building on the proven success of exendin-4/exenatide.","whyItMatters":"Diabetes affects nearly 500 million people worldwide. Natural venom peptides offer optimized molecular scaffolds that evolution has refined for billions of years, potentially yielding more effective drugs than synthetic design alone.","specificNumbers":"7+ species: Gila monster, bee, cone snail, sea anemone, scorpion, snake, spider; exenatide proof-of-concept","methodology":"Review of published literature on venom-derived peptide compounds with anti-diabetic potential, including drug development pathways from discovery through clinical trials.","limitations":"Review article without new experimental data. Many venom-derived compounds are in early research stages. Translation from animal venom to approved drug is lengthy and expensive."},{"rthcId":"RPEP-05329","title":"Anticipatory guidance and systematic review of prescribing combination incretin therapy in the treatment of type 2 diabetes.","authors":"Cowart, Kevin; Updike, Wendy H; Lloyd, Andie; Bullers, Krystal","year":2021,"journal":"Journal of clinical pharmacy and therapeutics, 46(1), 28-34","doi":"10.1111/jcpt.13270","pmid":"33067896","tags":["glp-1","diabetes","dosing","side-effects"],"studyType":"systematic-review","evidenceStrength":"moderate","keyFinding":"Combining GLP-1 RA and DPP-4 inhibitor provides only a small incremental reduction in HbA1c and weight loss, with the benefit unlikely to offset potential pancreatitis risk and additional cost.","whyItMatters":"Clinicians sometimes encounter patients on both drug classes, and understanding whether this combination is worthwhile prevents unnecessary polypharmacy, cost, and potential safety risks.","specificNumbers":"6 studies from 1,255 screened; small additional HbA1c and weight benefit; hypoglycemia, GI, pancreatitis infrequent","methodology":"Systematic literature review across five databases (1946-2020). Six studies meeting criteria analyzed for efficacy (HbA1c, weight) and safety (hypoglycemia, GI upset, pancreatitis).","limitations":"Only 6 studies met criteria, limiting the evidence base. Heterogeneity across studies in drug combinations, doses, and populations. Long-term outcomes not assessed."},{"rthcId":"RPEP-05330","title":"Appetite, the enteroendocrine system, gastrointestinal disease and obesity.","authors":"Crooks, Benjamin; Stamataki, Nikoleta S; McLaughlin, John T","year":2021,"journal":"The Proceedings of the Nutrition Society, 80(1), 50-58","doi":"10.1017/S0029665120006965","pmid":"32364087","tags":["glp-1","neuropeptides","weight-loss","gut-healing"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Postprandial gut peptide hormones may not play a dominant role in normal appetite regulation in healthy individuals; their impact may be more significant in GI disease states where levels become supraphysiological.","whyItMatters":"Billions of dollars are being invested in gut hormone-based therapies for obesity. Understanding the limitations of the gut hormone-appetite connection in healthy individuals may redirect research toward more effective targets.","specificNumbers":"CCK, PYY, GLP-1 discussed; largest endocrine system; hedonic > hormonal in normal appetite; supraphysiological levels in disease","methodology":"Narrative review of published evidence on enteroendocrine system function, gut peptide hormones, and appetite regulation in health and GI disease.","limitations":"Narrative review presenting a perspective — not a systematic analysis. The alternative hypothesis (hedonic/cognitive dominance) is also not fully proven."},{"rthcId":"RPEP-05331","title":"PepTherDia: database and structural composition analysis of approved peptide therapeutics and diagnostics.","authors":"D'Aloisio, Vera; Dognini, Paolo; Hutcheon, Gillian A; Coxon, Christopher R","year":2021,"journal":"Drug discovery today, 26(6), 1409-1419","doi":"10.1016/j.drudis.2021.02.019","pmid":"33647438","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05332","title":"Multiple potential roles of thymosin β4 in the growth and development of hair follicles.","authors":"Dai, Bai; Sha, Ri-Na; Yuan, Jian-Long; Liu, Dong-Jun","year":2021,"journal":"Journal of cellular and molecular medicine, 25(3), 1350-1358","doi":"10.1111/jcmm.16241","pmid":"33393222","tags":["thymosin-beta-4","skin-repair"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Both endogenous and exogenous thymosin β4 activate hair follicle cycling, promote stem cell migration and differentiation, and increase hair growth rate in animal models.","whyItMatters":"Hair loss affects millions of people worldwide with limited treatment options. Understanding how Tβ4 activates hair follicle stem cells could lead to new therapeutic approaches for various forms of alopecia.","specificNumbers":"Activates hair cycle; promotes stem cell migration; increased growth rate (mice); increased secondary follicles (goats)","methodology":"Review of published literature on thymosin β4's roles in hair follicle biology, including endogenous function and exogenous application studies in mice and cashmere goats.","limitations":"Review of animal model data — human hair follicle biology differs in important ways. Molecular mechanisms of Tβ4 in hair follicles remain incompletely understood. Clinical trials in humans are lacking."},{"rthcId":"RPEP-05333","title":"Oxytocin in young children with Prader-Willi syndrome: Results of a randomized, double-blind, placebo-controlled, crossover trial investigating 3 months of oxytocin.","authors":"Damen, Layla; Grootjen, Lionne N; Juriaans, Alicia F; Donze, Stephany H; Huisman, T Martin; Visser, Jenny A; Delhanty, Patric J D; Hokken-Koelega, Anita C S","year":2021,"journal":"Clinical endocrinology, 94(5), 774-785","doi":"10.1111/cen.14387","pmid":"33296519","tags":["oxytocin","nasal-peptides","anxiety-mood","weight-loss","clinical-trials"],"studyType":"rct","evidenceStrength":"moderate","keyFinding":"Intranasal oxytocin (16-40 IU/day for 3 months) improved social behavior and stabilized eating behavior in boys with PWS and in children with the deletion genotype, with no overall group effects.","whyItMatters":"PWS is characterized by severe behavioral challenges and uncontrollable hunger with no effective pharmacological treatment. Finding that oxytocin improves behavior in specific PWS subgroups opens a potential treatment avenue for this difficult condition.","specificNumbers":"26 children; 16-40 IU/day; 3 months; boys: +4.5 vs -4.0 (P=.025); hyperphagia 0.0 vs -3.5 (P=.046); deletion subtype improved; no SAEs","methodology":"Randomized, double-blind, placebo-controlled, crossover study in the Dutch PWS Reference Center. 26 children aged 3-11 years. Intranasal oxytocin 16-40 IU/day for 3 months. Outcomes: Oxytocin Questionnaire and Dykens hyperphagia questionnaire.","limitations":"Small sample size (n=26). Subgroup analyses (boys, deletion genotype) were not pre-specified primary outcomes. Crossover design assumes no carryover effects. Not all children showed benefit."},{"rthcId":"RPEP-05334","title":"CGRP Inhibitors and Oxidative Stress Biomarkers in Resistant Migraine: A Real-Life Study with Erenumab, Fremanezumab, and Galcanezumab.","authors":"De Luca, Ciro; Baldacci, Filippo; Mazzucchi, Sonia; Lombardo, Irene; Curto, Letizia; Ulivi, Martina; Chico, Lucia; Papa, Michele; Siciliano, Gabriele; Gori, Sara","year":2021,"journal":"Journal of clinical medicine, 10(19)","doi":"10.3390/jcm10194586","pmid":"34640604","tags":["neuropeptides","pain","clinical-trials"],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"CGRP inhibitors reduced AOPP (oxidative stress biomarker) over 6 months alongside 70% responder rates and significant improvements in disability, allodynia, fatigue, anxiety, and sleep quality in resistant migraineurs.","whyItMatters":"Treatment-resistant migraine patients represent the greatest clinical challenge. Showing that CGRP inhibitors not only reduce headaches but also improve oxidative stress and multiple comorbidities supports their use as transformative therapies for the most difficult cases.","specificNumbers":"70% 50% responders at 3 mo; ~25% 75% responders at 1 mo; AOPP decreased at 6 mo; allodynia moderate→mild; MIDAS improved","methodology":"Real-world prospective study in tertiary headache center patients with high-frequency resistant migraine and medication overuse headache. Three CGRP mAbs used (erenumab, fremanezumab, galcanezumab). Oxidative stress biomarkers, headache frequency, MIDAS, allodynia, and comorbidity measures assessed at 3 and 6 months.","limitations":"No control group. Real-world study without randomization or blinding. Small sample size implied. Oxidative stress is a biomarker with uncertain clinical significance in migraine."},{"rthcId":"RPEP-05335","title":"Effects of hydrolyzed collagen supplementation on skin aging: a systematic review and meta-analysis.","authors":"de Miranda, Roseane B; Weimer, Patrícia; Rossi, Rochele C","year":2021,"journal":"International journal of dermatology, 60(12), 1449-1461","doi":"10.1111/ijd.15518","pmid":"33742704","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05336","title":"Involvement of substance P, osteopontin and satellite glial cells on photobiomodulation-induced antinociceptive effect in an experimental model of dentin hypersensitivity.","authors":"de Oliveira, Victhor Teixeira; Ferrara-Jr, João Ignácio; Matielo, Heloísa Alonso; da Silva Alves, Adilson; Britto, Luiz Roberto; Aranha, Ana Cecilia Corrêa; Dale, Camila Squarzoni","year":2021,"journal":"Lasers in medical science, 36(6), 1297-1305","doi":"10.1007/s10103-021-03246-9","pmid":"33452567","tags":["neuropeptides","pain"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"PBM at 660nm and 808nm reversed dentin hypersensitivity by reducing substance P in the dentin-pulp complex and trigeminal ganglia, suppressing glial activation (GFAP), and increasing osteopontin expression for tissue repair.","whyItMatters":"Dentin hypersensitivity affects up to 57% of the population. Understanding that light therapy works by reducing pain-neuropeptide signaling and promoting repair — not just symptom masking — validates its use as a mechanistic dental treatment.","specificNumbers":"660nm and 808nm; 1J, 3.5 J/cm2, 100mW, 10s, 3 sessions; SP reduced in pulp + TG; GFAP reduced; OPN increased at 14d","methodology":"Rat model: 45-day acidic isotonic drink ingestion to induce dentin hypersensitivity. PBM: 660nm or 808nm, 1J, 3.5 J/cm², 100mW, 10s, 3 consecutive daily sessions. Nociceptive behavior assessed at 24h, 48h, 72h, and 14 days. Immunohistochemistry for substance P, GFAP, and osteopontin.","limitations":"Rat model — dental anatomy and pain processing differ from humans. Single acid exposure model may not represent all clinical causes of dentin hypersensitivity. Specific laser parameters may need optimization for human clinical use."},{"rthcId":"RPEP-05337","title":"BPC 157 as Potential Treatment for COVID-19.","authors":"Deek, Sarah A","year":2021,"journal":"Medical hypotheses, 158, 110736","doi":"10.1016/j.mehy.2021.110736","pmid":"34798584","tags":["bpc-157","cardiovascular","inflammation","infection"],"studyType":"hypothesis","evidenceStrength":"preliminary","keyFinding":"BPC 157's demonstrated eNOS activation, NO-mediated tissue repair, and angiomodulatory properties in animal models provide a theoretical basis for its use as a complementary treatment for COVID-19's endothelial and multi-organ damage.","whyItMatters":"COVID-19 caused millions of deaths partly through vascular damage and multi-organ failure. Identifying agents that protect the vascular endothelium could improve outcomes and provide treatment options for the vascular complications of this and future pandemic viruses.","specificNumbers":"eNOS activation; NO release; endothelial protection; anti-inflammatory; cytoprotective; all from animal models","methodology":"Medical hypothesis paper reviewing existing animal model evidence for BPC 157's vascular and organ protective effects, applied to COVID-19 pathophysiology.","limitations":"Hypothesis paper based on animal model data — no human COVID-19 clinical trial data. BPC 157 lacks FDA approval and comprehensive human safety data. Theoretical extrapolation from other conditions to COVID-19."},{"rthcId":"RPEP-05338","title":"Protective immune response against P32 oncogenic peptide-pulsed PBMCs in mouse models of breast cancer.","authors":"Dehghan-Manshadi, Mahdi; Nikpoor, Amin Reza; Hadinedoushan, Hossein; Zare, Fateme; Sankian, Mojtaba; Fesahat, Farzaneh; Rafatpanah, Houshang","year":2021,"journal":"International immunopharmacology, 93, 107414","doi":"10.1016/j.intimp.2021.107414","pmid":"33578183","tags":["cancer","immune-function"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"F4 peptide from P32 protein delivered via CpG-adjuvanted PBMCs or DCs induced protective immune responses with smaller tumors and prolonged survival in a mouse breast cancer model, with PBMCs offering a simpler alternative to DCs.","whyItMatters":"Breast cancer remains a leading cause of cancer death worldwide. A simple, cost-effective peptide vaccine that can be prepared with PBMCs (avoiding the complexity of dendritic cell isolation) could make cancer immunotherapy more accessible.","specificNumbers":"160 mice; 5 groups/peptide; increased IFN-γ, granzyme B, FasL, Caspase3; decreased Foxp3; smaller tumors; longer survival","methodology":"160 BALB/c mice vaccinated in 5 subgroups per peptide (PBS, peptide alone, peptide+CpG, peptide+CpG+DCs, peptide+CpG+PBMCs). Immune responses: IFN-γ, granzyme B, FasL, Foxp3, Caspase3 by ELISPOT, ELISA, and gene expression. Tumor challenge with 4T1 cells.","limitations":"Mouse model with transplanted tumor — may not reflect spontaneous human breast cancer. Single tumor cell line (4T1). Prophylactic rather than therapeutic vaccination. Specific epitope sequences not detailed in abstract."},{"rthcId":"RPEP-05339","title":"A positive feedback loop between mTORC1 and cathelicidin promotes skin inflammation in rosacea.","authors":"Deng, Zhili; Chen, Mengting; Liu, Yingzi; Xu, San; Ouyang, Yuyan; Shi, Wei; Jian, Dan; Wang, Ben; Liu, Fangfen; Li, Jinmao; Shi, Qian; Peng, Qinqin; Sha, Ke; Xiao, Wenqin; Liu, Tangxiele; Zhang, Yiya; Zhang, Hongbing; Wang, Qian; Sun, Lunquan; Xie, Hongfu; Li, Ji","year":2021,"journal":"EMBO molecular medicine, 13(5), e13560","doi":"10.15252/emmm.202013560","pmid":"33734592","tags":["ll-37","inflammation","skin-repair","receptor-signaling"],"studyType":"animal + human observational","evidenceStrength":"moderate","keyFinding":"Cathelicidin LL37 activates mTORC1 via TLR2, and mTORC1 increases cathelicidin expression, creating a positive feedback loop driving rosacea. Topical rapamycin broke this cycle and improved patient symptoms.","whyItMatters":"Rosacea affects millions with limited treatment options. Identifying a specific molecular loop that perpetuates the disease — and showing that an existing drug (rapamycin) can break it — provides both mechanistic understanding and a immediately actionable therapeutic approach.","specificNumbers":"mTORC1 hyperactivation in rosacea epidermis; topical rapamycin improved clinical symptoms; LL37 activates mTORC1 via TLR2","methodology":"Human rosacea skin biopsies. LL37-induced mouse rosacea model. Epithelium-specific mTORC1 knockout and hyperactivation. mTORC1 inhibitor treatment. NF-κB activation and cytokine profiling. Clinical application of topical rapamycin in rosacea patients.","limitations":"Mouse rosacea model uses exogenous LL37 injection which may not perfectly replicate spontaneous human disease. Clinical rapamycin data appears preliminary. Long-term safety of topical rapamycin for rosacea not established."},{"rthcId":"RPEP-05340","title":"Artificial Intelligence Identified Resilient and Vulnerable Female Rats After Traumatic Stress and Ethanol Exposure: Investigation of Neuropeptide Y Pathway Regulation.","authors":"Denny, Ray R; Connelly, Krista L; Ghilotti, Marco G; Meissler, Joseph J; Yu, Daohai; Eisenstein, Toby K; Unterwald, Ellen M","year":2021,"journal":"Frontiers in neuroscience, 15, 772946","doi":"10.3389/fnins.2021.772946","pmid":"34975380","tags":["neuropeptides","anxiety-mood","addiction"],"studyType":"animal","evidenceStrength":"low","keyFinding":"Resilient female rats had higher Y2R mRNA expression in the central amygdala and higher NPY protein levels in the BNST compared to vulnerable and control rats after traumatic stress exposure.","whyItMatters":"Understanding why some individuals are resilient to trauma while others develop PTSD could lead to NPY-based prevention or treatment strategies for stress-related disorders and co-occurring alcohol use disorder.","specificNumbers":"Higher Y2R mRNA in CeA; higher NPY in BNST; 8-week intermittent ethanol drinking period; open field and elevated plus maze testing","methodology":"Animal study using single prolonged stress (SPS) in female rats. An AI classification algorithm was trained on anxiety behavior and ethanol consumption data, then applied to a second cohort. NPY protein and receptor mRNA were measured in amygdala and BNST regions.","limitations":"Animal model only using female rats, so findings may not directly translate to humans. The AI classification system has not been validated in clinical populations. The study did not test whether boosting NPY could shift vulnerable animals toward resilience."},{"rthcId":"RPEP-05341","title":"Cell-penetrating peptides (CPPs): an overview of applications for improving the potential of nanotherapeutics.","authors":"Desale, Kalyani; Kuche, Kaushik; Jain, Sanyog","year":2021,"journal":"Biomaterials science, 9(4), 1153-1188","doi":"10.1039/d0bm01755h","pmid":"33355322","tags":["cell-penetrating","peptide-delivery","cancer"],"studyType":"review","evidenceStrength":"n/a (review)","keyFinding":"CPPs can effectively assist nanotherapeutics in crossing cell membranes, with demonstrated applications in cancer therapy, tumor imaging, atherosclerosis evaluation, thrombin detection, and HIV therapy.","whyItMatters":"Drug delivery remains one of the biggest bottlenecks in medicine. CPPs provide a versatile, peptide-based solution that could make many existing and experimental therapies significantly more effective by solving the cellular entry problem.","specificNumbers":"Covers cancer therapy, tumor imaging, atherosclerotic plaques, thrombin levels, and HIV therapy","methodology":"Narrative review of published literature covering CPP mechanisms, therapeutic applications, tumor imaging uses, nanocarrier enhancement, stability challenges, and strategies to overcome them.","limitations":"Review article with no new experimental data. CPP stability, off-target delivery, and potential immunogenicity remain unsolved challenges. Most applications discussed are still preclinical."},{"rthcId":"RPEP-05342","title":"Insights into a possible role of glucagon-like peptide-1 receptor agonists in the treatment of depression.","authors":"Detka, Jan; Głombik, Katarzyna","year":2021,"journal":"Pharmacological reports : PR, 73(4), 1020-1032","doi":"10.1007/s43440-021-00274-8","pmid":"34003475","tags":["glp-1","anxiety-mood","neuroprotection","inflammation"],"studyType":"review","evidenceStrength":"n/a (review)","keyFinding":"GLP-1 receptor agonists demonstrate potential antidepressant effects through multiple mechanisms: neuroprotection, anti-inflammatory action, stress response modulation, brain energy metabolism improvement, and gut-brain axis stabilization.","whyItMatters":"Depression and metabolic disorders share biological pathways. GLP-1 drugs that address both conditions simultaneously could transform treatment for the millions of patients who suffer from overlapping mood and metabolic problems.","specificNumbers":"Depression co-occurs with T2DM and obesity; GLP-1RAs target neurotrophic factors, immune-endocrine homeostasis, brain energy metabolism, and gut microbiota","methodology":"Narrative review of preclinical and clinical literature examining GLP-1RA effects on depression-related biological pathways including neurotrophic factors, immune-endocrine homeostasis, energy metabolism, and gut microbiota.","limitations":"Review article with no new experimental data. Most supporting evidence comes from animal models. Large-scale randomized controlled trials specifically testing GLP-1RAs for depression in humans are still needed."},{"rthcId":"RPEP-05343","title":"Strategies for the delivery of antidiabetic drugs via intranasal route.","authors":"Dholakia, Jheel; Prabhakar, Bala; Shende, Pravin","year":2021,"journal":"International journal of pharmaceutics, 608, 121068","doi":"10.1016/j.ijpharm.2021.121068","pmid":"34481011","tags":["glp-1","diabetes","nasal-peptides","bioavailability","peptide-delivery"],"studyType":"review","evidenceStrength":"n/a (review)","keyFinding":"Intranasal delivery of insulin and glucagon-like peptides demonstrates improved therapeutic levels and patient compliance, with drugs transported through epithelial tight junctions via the paracellular route.","whyItMatters":"Needle-free delivery of peptide drugs like insulin and GLP-1 agonists could transform daily diabetes management, improving quality of life and treatment adherence for hundreds of millions of patients worldwide.","specificNumbers":"Strategies: polymers, particulate systems, peptide complexation, glucose-responsive systems; paracellular transport through epithelial tight junctions","methodology":"Narrative review of published literature covering intranasal antidiabetic formulation strategies, absorption mechanisms, challenges, and emerging technologies like glucose-responsive delivery systems.","limitations":"Review with mostly preclinical data. Nasal delivery faces real-world challenges including enzyme degradation, mucociliary clearance, limited nasal cavity volume, and potential irritation. Very few products have reached clinical trials."},{"rthcId":"RPEP-05344","title":"Self-Supporting Hydrogels Based on Fmoc-Derivatized Cationic Hexapeptides for Potential Biomedical Applications.","authors":"Diaferia, Carlo; Rosa, Elisabetta; Gallo, Enrico; Smaldone, Giovanni; Stornaiuolo, Mariano; Morelli, Giancarlo; Accardo, Antonella","year":2021,"journal":"Biomedicines, 9(6)","doi":"10.3390/biomedicines9060678","pmid":"34203919","tags":["peptide-design","peptide-delivery","wound-healing"],"studyType":"in vitro","evidenceStrength":"low","keyFinding":"Fmoc-K3 hexapeptide hydrogel achieved a storage modulus of 2,526 Pa and fully supported cell adhesion, survival, and duplication, demonstrating potential as a tissue engineering scaffold.","whyItMatters":"Tissue engineering needs biocompatible scaffolds that cells can grow on. Simple peptide-based hydrogels are attractive because they are biodegradable, customizable, and can be designed from short amino acid sequences without complex manufacturing.","specificNumbers":"6 analogues; Fmoc-K3 G' = 2526 Pa; forces: van der Waals, hydrogen bonding, pi-pi stacking","methodology":"In vitro study. Six Fmoc-derivatized cationic hexapeptide analogues were synthesized and characterized for self-assembly and gelation using biophysical techniques. Cell adhesion and viability were tested on the resulting hydrogels.","limitations":"In vitro only — no animal or human testing. Only basic cell adhesion and viability assessed; functional tissue formation was not demonstrated. Long-term stability and degradation behavior were not characterized."},{"rthcId":"RPEP-05345","title":"Effect of aerobic and resistance exercise on the mitochondrial peptide MOTS-c in Hispanic and Non-Hispanic White breast cancer survivors.","authors":"Dieli-Conwright, Christina M; Sami, Nathalie; Norris, Mary K; Wan, Junxiang; Kumagai, Hiroshi; Kim, Su-Jeong; Cohen, Pinchas","year":2021,"journal":"Scientific reports, 11(1), 16916","doi":"10.1038/s41598-021-96419-z","pmid":"34413391","tags":["anti-aging","cancer","hormone-optimization"],"studyType":"randomized controlled trial (secondary analysis)","evidenceStrength":"moderate","keyFinding":"A 16-week aerobic and resistance exercise intervention significantly increased MOTS-c levels in non-Hispanic White breast cancer survivors, with post-exercise MOTS-c associated with reductions in fat mass, body weight, HOMA-IR, and CRP, and increased lean mass (p < 0.01).","whyItMatters":"This connects the benefits of exercise to a specific mitochondrial peptide, suggesting MOTS-c may partly explain how exercise protects cancer survivors from metabolic complications. Ethnic differences in response highlight the need for personalized approaches.","specificNumbers":"25 Hispanic + 24 non-Hispanic White BCS; 16-week intervention; p < 0.01 for MOTS-c associations with fat mass, body weight, HOMA-IR, CRP, lean mass","methodology":"Randomized controlled trial (secondary analysis). Stage I-III breast cancer survivors randomized to 16-week aerobic plus resistance exercise or standard care. Fasting plasma MOTS-c measured by in-house ELISA. Statistical analysis via paired t-test and repeated measures ANOVA.","limitations":"Secondary analysis with small sample size (49 total). MOTS-c response differed by ethnicity, possibly confounded by baseline metabolic differences. In-house ELISA used for MOTS-c measurement may limit reproducibility. Exercise intervention effects cannot be isolated to MOTS-c alone."},{"rthcId":"RPEP-05346","title":"Substance P containing peptide gene delivery vectors for specifically transfecting glioma cells mediated by a neurokinin-1 receptor.","authors":"Ding, Guihua; Wang, Taoran; Han, Zhenbin; Tian, Long; Cheng, Qin; Luo, Longlong; Zhao, Baoquan; Wang, Chenhong; Feng, Siliang; Wang, Lianshuai; Meng, Zhao; Meng, Qingbin","year":2021,"journal":"Journal of materials chemistry. B, 9(32), 6347-6356","doi":"10.1039/d1tb00577d","pmid":"34251002","tags":["neuropeptides","cell-penetrating","cancer","peptide-delivery"],"studyType":"in vitro + animal (zebrafish)","evidenceStrength":"low","keyFinding":"Peptide vector P-02 (SP-PEG4-K(C18)-(LLHH)3-R9) achieved 36% higher transfection in glioma U87 cells versus normal 293T cells, with NK1 receptor-mediated targeting confirmed. The vector crossed a BBB model in vitro and achieved gene expression in zebrafish brain.","whyItMatters":"Glioblastoma is the deadliest brain cancer with few effective treatments. A peptide delivery system that can both cross the blood-brain barrier and selectively target tumor cells could make gene therapy a viable treatment option.","specificNumbers":"36% higher transfection ratio in U87 vs 293T; NK1R-mediated; BBB model crossed; EGFP expression in zebrafish brain","methodology":"In vitro and zebrafish study. Peptide vectors with substance P targeting, cell-penetrating, and endosomal escape segments were synthesized. Gene transfection tested in U87 glioma, 293T-NK1R, and normal 293T cells. BBB crossing assessed in vitro and in zebrafish.","limitations":"Preclinical only — in vitro cell lines and zebrafish model. No mammalian in vivo data. Transfection efficiency compared to established methods remains modest. Long-term safety, immune response, and therapeutic gene payload effects not assessed."},{"rthcId":"RPEP-05347","title":"Mitochondrial dysfunction and beneficial effects of mitochondria-targeted small peptide SS-31 in Diabetes Mellitus and Alzheimer's disease.","authors":"Ding, Xiao-Wen; Robinson, Megan; Li, Rongzi; Aldhowayan, Hadeel; Geetha, Thangiah; Babu, Jeganathan Ramesh","year":2021,"journal":"Pharmacological research, 171, 105783","doi":"10.1016/j.phrs.2021.105783","pmid":"34302976","tags":["neuroprotection","diabetes","anti-aging","peptide-delivery"],"studyType":"review","evidenceStrength":"n/a (review)","keyFinding":"SS-31 peptide targets mitochondria directly, inhibiting oxidative stress and restoring mitochondrial function with greater therapeutic potential than traditional antioxidants like vitamin E in models of diabetes and Alzheimer's disease.","whyItMatters":"Diabetes and Alzheimer's are two of the most common chronic diseases with inadequate treatments. A peptide that addresses their shared mitochondrial dysfunction could offer a fundamentally different therapeutic approach from current drugs.","specificNumbers":"SS-31 concentrates in mitochondria; inhibits reactive oxygen species; superior to vitamin E in models","methodology":"Narrative review summarizing pathophysiological evidence of mitochondrial dysfunction in diabetes and Alzheimer's disease, and the beneficial effects of SS-31 peptide compared to conventional antioxidants.","limitations":"Review article with no new experimental data. Most SS-31 evidence for diabetes and Alzheimer's comes from preclinical models. Clinical trial data for these specific conditions is limited. The relationship between mitochondrial dysfunction and disease causation is still being clarified."},{"rthcId":"RPEP-05348","title":"Personalized neoantigen pulsed dendritic cell vaccine for advanced lung cancer.","authors":"Ding, Zhenyu; Li, Qing; Zhang, Rui; Xie, Li; Shu, Yang; Gao, Song; Wang, Peipei; Su, Xiaoqing; Qin, Yun; Wang, Yuelan; Fang, Juemin; Zhu, Zhongzheng; Xia, Xuyang; Wei, Guochao; Wang, Hui; Qian, Hong; Guo, Xianling; Gao, Zhibo; Wang, Yu; Wei, Yuquan; Xu, Qing; Xu, Heng; Yang, Li","year":2021,"journal":"Signal transduction and targeted therapy, 6(1), 26","doi":"10.1038/s41392-020-00448-5","pmid":"33473101","tags":["cancer","immune-function","peptide-design","clinical-trials"],"studyType":"clinical trial (pilot, single-arm)","evidenceStrength":"low","keyFinding":"In 12 advanced lung cancer patients, personalized neoantigen DC vaccine achieved 25% objective response rate, 75% disease control rate, 5.5-month median progression-free survival, and 7.9-month median overall survival with only grade 1-2 adverse events.","whyItMatters":"Lung cancer is the deadliest cancer worldwide, and many patients exhaust standard treatment options. Personalized neoantigen vaccines represent a fundamentally different approach that trains the immune system to specifically target each patient's unique tumor.","specificNumbers":"12 patients; 85 vaccine treatments; median 5 doses/person; 12-30 neoantigens/patient; ORR 25%; DCR 75%; mPFS 5.5 months; mOS 7.9 months; all AEs grade 1-2","methodology":"Single-arm, 2-center pilot study. Whole-exome and RNA sequencing of tumor biopsies identified candidate neoantigens. 12-30 neoantigen peptides per patient were used to pulse autologous dendritic cells. 85 total vaccine treatments administered (median 5 doses/person, range 3-14).","limitations":"Very small sample size (12 patients). Single-arm design without a control group. All patients were heavily pretreated, making it difficult to compare outcomes. Neoantigen identification and vaccine production are complex and time-consuming. Requires fresh tumor biopsy material."},{"rthcId":"RPEP-05349","title":"Exosome-mediated delivery of an anti-angiogenic peptide inhibits pathological retinal angiogenesis.","authors":"Dong, Xue; Lei, Yi; Yu, Zeyang; Wang, Tian; Liu, Yi; Han, Gang; Zhang, Xiaodan; Li, Yiming; Song, Yinting; Xu, Heping; Du, Mei; Yin, Haifang; Wang, Xiaohong; Yan, Hua","year":2021,"journal":"Theranostics, 11(11), 5107-5126","doi":"10.7150/thno.54755","pmid":"33859737","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05350","title":"Deficiency of Cathelicidin-related Antimicrobial Peptide Promotes Skin Papillomatosis in Mus musculus Papillomavirus 1-infected Mice.","authors":"Dorfer, Sonja; Strasser, Katharina; Reipert, Siegfried; Fischer, Michael B; Shafti-Keramat, Saeed; Bonelli, Michael; Schröckenfuchs, Georg; Bauer, Wolfgang; Kancz, Stefanie; Müller, Lena; Handisurya, Alessandra","year":2021,"journal":"Acta dermato-venereologica, 101(1), adv00367","doi":"10.2340/00015555-3733","pmid":"33349888","tags":["ll-37","antimicrobial-peptides","immune-function","infection"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"CRAMP-deficient mice developed robust skin papillomas after papillomavirus infection while wild-type mice did not. Protection was primarily immune-mediated: CRAMP-deficient mice showed reduced CD4+ and CD8+ T cells and lacked virus-specific neutralizing antibodies.","whyItMatters":"This is the first in vivo evidence that cathelicidin antimicrobial peptides protect against papillomavirus infection, primarily by enhancing immune responses. This could inform new prevention or treatment strategies for HPV-related diseases in humans.","specificNumbers":"Robust papillomas in CRAMP-deficient mice; none in wild-type; reduced CD4+ and CD8+ T cells; no neutralizing antibodies without CRAMP","methodology":"Animal study. CRAMP-deficient and wild-type C57BL/6J mice were treated with cyclosporine A and experimentally infected with mouse papillomavirus 1. Papilloma development, immune cell counts, neutralizing antibody levels, and direct antiviral effects of synthetic CRAMP were analyzed.","limitations":"Mouse model with cyclosporine A immunosuppression, which may amplify cathelicidin's protective role. Mouse papillomavirus differs from human HPV. CRAMP is not identical to human LL-37. Sample size not reported."},{"rthcId":"RPEP-05351","title":"Anti-inflammatory activities of arthropod peptides: a systematic review.","authors":"Dos Santos, Ariane Teixeira; Cruz, Gabriela Silva; Baptista, Gandhi Rádis","year":2021,"journal":"The journal of venomous animals and toxins including tropical diseases, 27, e20200152","doi":"10.1590/1678-9199-JVATITD-2020-0152","pmid":"34795699","tags":["venom-peptides","inflammation","antimicrobial-peptides","cancer"],"studyType":"systematic review","evidenceStrength":"n/a (review)","keyFinding":"From 171 reviewed studies, arthropod-derived peptides from 9 animal groups demonstrated anti-inflammatory activity, primarily by decreasing pro-inflammatory cytokines in vitro and in vivo, with some also exhibiting anticancer properties.","whyItMatters":"Current anti-inflammatory drugs often have significant side effects. Arthropod venom peptides offer a diverse library of natural anti-inflammatory molecules that could lead to new, more targeted treatments with fewer adverse effects.","specificNumbers":"171 studies; 9 peptide families; sources: ants, bees, wasps, shrimp, crabs, scorpions, spiders, ticks, centipedes","methodology":"Systematic review following PRISMA guidelines. PubMed, Scopus, Web of Science, and Google Scholar searched with no publication date limit. 171 studies met inclusion/exclusion criteria for data extraction.","limitations":"Systematic review with no new experimental data. Most included studies used in vitro or animal models. Clinical translation of venom peptides faces significant challenges including toxicity, stability, and manufacturing. Human safety data is largely absent."},{"rthcId":"RPEP-05352","title":"Recent Applications of Retro-Inverso Peptides.","authors":"Doti, Nunzianna; Mardirossian, Mario; Sandomenico, Annamaria; Ruvo, Menotti; Caporale, Andrea","year":2021,"journal":"International journal of molecular sciences, 22(16)","doi":"10.3390/ijms22168677","pmid":"34445382","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05353","title":"Sedative-Hypnotic Agents That Impact Gamma-Aminobutyric Acid Receptors: Focus on Flunitrazepam, Gamma-Hydroxybutyric Acid, Phenibut, and Selank.","authors":"Doyno, Cassandra R; White, C Michael","year":2021,"journal":"Journal of clinical pharmacology, 61 Suppl 2, S114-S128","doi":"10.1002/jcph.1922","pmid":"34396551","tags":["selank","anxiety-mood","peptide-safety","sleep"],"studyType":"review","evidenceStrength":"n/a (review)","keyFinding":"Selank and phenibut are poorly studied GABAergic drugs sold as US dietary supplements. Phenibut poison control calls have increased substantially, and both carry risks of dependence, withdrawal, and serious adverse effects when misused.","whyItMatters":"People are buying selank and phenibut without prescriptions, often unaware of their risks. This review highlights the regulatory gap that allows poorly studied GABAergic peptides and drugs to be sold as supplements.","specificNumbers":"Phenibut poison control calls rising over 5 years; high-dose GABA drugs cause respiratory depression, coma, death; chronic use causes dependence and withdrawal","methodology":"Narrative review of pharmacology, clinical effects, abuse potential, and safety profiles of selected GABAergic agents including flunitrazepam, GHB, phenibut, and selank.","limitations":"Narrative review, not systematic. Very limited clinical data on selank specifically — most information comes from Russian literature that may not meet international standards. The review groups selank with much more dangerous substances, which may overstate its individual risk profile."},{"rthcId":"RPEP-05354","title":"Comparative efficacy of 5 sodium glucose cotransporter 2 inhibitor and 7 glucagon-like peptide 1 receptor agonists interventions on cardiorenal outcomes in type 2 diabetes patients: A network meta-analysis based on cardiovascular or renal outcome trials.","authors":"Duan, Xue-Yan; Liu, Shu-Yan; Yin, Dao-Gen","year":2021,"journal":"Medicine, 100(30), e26431","doi":"10.1097/MD.0000000000026431","pmid":"34397684","tags":["glp-1","semaglutide","diabetes","cardiovascular","kidney"],"studyType":"network meta-analysis","evidenceStrength":"high","keyFinding":"Sotagliflozin ranked first for MACE (HR 0.76), heart failure hospitalization (HR 0.59), MI (HR 0.65), and stroke (HR 0.56). Empagliflozin and dapagliflozin led for kidney protection. Oral semaglutide and empagliflozin were best for all-cause death reduction.","whyItMatters":"Not all GLP-1 and SGLT2 drugs are equal for heart and kidney protection. This analysis gives clinicians evidence to match specific drugs to each patient's most important cardiovascular or renal risks.","specificNumbers":"14 CVOTs; sotagliflozin MACE HR 0.76; HHF HR 0.59; MI HR 0.65; stroke HR 0.56; oral semaglutide and empagliflozin best for all-cause death","methodology":"Bayesian network meta-analysis of 14 cardiovascular or renal outcome trials (CVOTs) from PubMed and Embase. Endpoints: MACE, stroke, MI, cardiovascular death, all-cause death, kidney function progression, and heart failure hospitalization. Hazard ratios with 95% CI and SUCRA rankings calculated.","limitations":"Network meta-analysis uses indirect comparisons between trials with different patient populations, follow-up durations, and baseline risks. Some drug-to-drug comparisons had wide confidence intervals. Sotagliflozin trials included heart failure patients, potentially inflating its cardiovascular benefit."},{"rthcId":"RPEP-05355","title":"Experimentally induced spine osteoarthritis in rats leads to neurogenic inflammation within neurosegmentally linked myotomes.","authors":"Duarte, Felipe C K; Hurtig, Mark; Clark, Andrea; Brown, Stephen; Simpson, Jeremy; Srbely, John","year":2021,"journal":"Experimental gerontology, 149, 111311","doi":"10.1016/j.exger.2021.111311","pmid":"33744392","tags":["neuropeptides","pain","inflammation","bone-joint"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"Spine facet osteoarthritis increased substance P, CGRP, PAR2, and CaMKII in neurosegmentally linked rectus femoris muscle but not in unlinked biceps brachii, with pain sensitization (allodynia, thermal hyperalgesia) at 7, 14, and 21 days post-surgery.","whyItMatters":"This is the first direct evidence linking spine arthritis to neurogenic inflammation in specific muscles. It explains why back pain patients often develop chronic muscle problems and suggests that targeting neuropeptides like substance P and CGRP could treat both the joint and muscle components of osteoarthritis pain.","specificNumbers":"Elevated SP, CGRP, PAR2, CaMKII in rectus femoris; no changes in biceps brachii; allodynia and hyperalgesia at 7, 14, 21 days","methodology":"Randomized controlled animal study. Wistar Kyoto rats underwent facet compression surgery (L4-L6) or sham surgery. Sensory testing at 7, 14, and 21 days. Neuropeptide biomarkers (substance P, CGRP, PAR2, CaMKII) measured in segmentally linked and unlinked muscles.","limitations":"Animal model with surgically induced osteoarthritis, which may differ from naturally developing disease. Only two muscles compared. Sample size not reported. Short follow-up period (21 days) may not capture chronic disease progression."},{"rthcId":"RPEP-05356","title":"Efficacy and safety of novel twincretin tirzepatide a dual GIP and GLP-1 receptor agonist in the management of type-2 diabetes: A Cochrane meta-analysis.","authors":"Dutta, Deep; Surana, Vineet; Singla, Rajiv; Aggarwal, Sameer; Sharma, Meha","year":2021,"journal":"Indian journal of endocrinology and metabolism, 25(6), 475-489","doi":"10.4103/ijem.ijem_423_21","pmid":"35355921","tags":["tirzepatide","diabetes","weight-loss","glp-1"],"studyType":"meta-analysis","evidenceStrength":"high","keyFinding":"Tirzepatide reduced HbA1c by an additional 0.75%, weight by 8.63 kg, BMI by 1.80 kg/m², and waist circumference by 4.43 cm versus active comparators. Odds of >15% weight loss were 32.8 times higher with tirzepatide.","whyItMatters":"Tirzepatide's dual GIP/GLP-1 mechanism delivers superior blood sugar control and weight loss compared to drugs targeting GLP-1 alone, potentially establishing a new standard of care for type 2 diabetes.","specificNumbers":"6 RCTs; 3,484 patients; HbA1c MD -0.75%; FPG -0.75 mmol/L; weight -8.63 kg; BMI -1.80 kg/m2; waist -4.43 cm; >5% weight loss OR 19.18; >10% OR 21.40; >15% OR 32.84","methodology":"Cochrane meta-analysis of 6 RCTs (3,484 patients) comparing tirzepatide to dulaglutide, semaglutide, insulin degludec, and insulin glargine over 12-52 weeks. Primary outcome: HbA1c change. Secondary: glucose, weight, lipids, adverse events.","limitations":"Very high heterogeneity (I² up to 100%) across included trials. Publication bias detected. Evidence graded moderate to low. Most trials were industry-funded. Maximum follow-up was 52 weeks — long-term cardiovascular outcomes unknown at time of analysis."},{"rthcId":"RPEP-05357","title":"PLGA Nanoparticles Co-encapsulating NY-ESO-1 Peptides and IMM60 Induce Robust CD8 and CD4 T Cell and B Cell Responses.","authors":"Dölen, Yusuf; Gileadi, Uzi; Chen, Ji-Li; Valente, Michael; Creemers, Jeroen H A; Van Dinther, Eric A W; van Riessen, N Koen; Jäger, Eliezer; Hruby, Martin; Cerundolo, Vincenzo; Diken, Mustafa; Figdor, Carl G; de Vries, I Jolanda M","year":2021,"journal":"Frontiers in immunology, 12, 641703","doi":"10.3389/fimmu.2021.641703","pmid":"33717196","tags":["cancer","immune-function","peptide-delivery","peptide-design"],"studyType":"preclinical (in vitro + animal)","evidenceStrength":"low","keyFinding":"PLGA nanoparticles co-delivering three NY-ESO-1 peptide sequences and IMM60 iNKT cell agonist enhanced CD4 and CD8 T cell responses and antibody levels in vivo, with negligible systemic toxicity and GMP-compatible production.","whyItMatters":"An off-the-shelf cancer vaccine that triggers both killer and helper immune responses could be produced quickly at scale, unlike personalized vaccines that must be custom-made for each patient.","specificNumbers":"3 peptide sequences (85-111, 117-143, 157-165); wide HLA coverage; GMP-compatible; negligible systemic toxicity at high doses","methodology":"Preclinical study. PLGA nanoparticles formulated with three NY-ESO-1 peptides (residues 85-111, 117-143, 157-165) and IMM60. Dendritic cell processing and HLA presentation tested in vitro. Immunogenicity and toxicity assessed in vivo.","limitations":"Preclinical only — not tested in human cancer patients. NY-ESO-1 is not expressed in all tumor types, limiting the patient population. Long-term immune memory and anti-tumor efficacy against established tumors were not evaluated."},{"rthcId":"RPEP-05358","title":"Racial, Ethnic, and Socioeconomic Inequities in Glucagon-Like Peptide-1 Receptor Agonist Use Among Patients With Diabetes in the US.","authors":"Eberly, Lauren A; Yang, Lin; Essien, Utibe R; Eneanya, Nwamaka D; Julien, Howard M; Luo, Jing; Nathan, Ashwin S; Khatana, Sameed Ahmed M; Dayoub, Elias J; Fanaroff, Alexander C; Giri, Jay; Groeneveld, Peter W; Adusumalli, Srinath","year":2021,"journal":"JAMA health forum, 2(12), e214182","doi":"10.1001/jamahealthforum.2021.4182","pmid":"35977298","tags":["glp-1-agonists","health-disparities","type-2-diabetes"],"studyType":"Retrospective Cohort Study","evidenceStrength":"Strong","keyFinding":"Among 1.18 million commercially insured US patients with type 2 diabetes, only 7.7% received a GLP-1 receptor agonist between 2015 and 2019. Use increased over that period (3.2% to 10.7%), but significant racial and economic disparities persisted. Black patients were 19% less likely to receive a GLP-1 RA (aOR 0.81), Asian patients were 41% less likely (aOR 0.59), and Hispanic patients were 9% less likely (aOR 0.91) compared to White patients.\n\nHigher household income was associated with greater GLP-1 RA use — patients from zip codes with incomes over $100,000 were 13% more likely to receive these drugs than those from areas with incomes below $50,000. Even among patients with established cardiovascular disease — the group most likely to benefit from GLP-1 RAs based on clinical trial evidence — use remained low (2.8% to 9.4%) with similar racial and income disparities.","whyItMatters":"GLP-1 receptor agonists don't just lower blood sugar — they reduce heart attacks, strokes, and cardiovascular death. Yet the patients who carry the highest burden of cardiovascular disease (Black, Hispanic, and lower-income individuals) are the least likely to receive these drugs. This study quantifies a prescribing gap that could be widening existing health disparities, especially as GLP-1 drugs have become among the most impactful medications in modern medicine.","specificNumbers":"n=1,180,260 · 7.7% received GLP-1 RA · use grew 3.2% → 10.7% (2015–2019) · Black aOR 0.81 · Asian aOR 0.59 · Hispanic aOR 0.91 · income >$100K aOR 1.13 · ASCVD subgroup: 2.8% → 9.4%","methodology":"Retrospective cohort analysis using OptumInsight Clinformatics Data Mart, a large commercial insurance claims database. Included adult patients with type 2 diabetes from October 2015 through June 2019. Multivariable logistic regression models assessed associations between race, ethnicity, sex, zip code-linked income, and GLP-1 RA prescribing. A subgroup analysis focused on patients with established atherosclerotic cardiovascular disease.","limitations":"Limited to commercially insured patients, excluding uninsured and Medicaid populations where disparities may be even larger. Race and ethnicity data in claims databases can be imprecise. Zip code-level income is a proxy for individual socioeconomic status. The study captures prescriptions but not adherence or outcomes. Reasons for non-prescribing (cost, patient preference, provider knowledge) were not assessed. Data ended in 2019, before the explosion of GLP-1 RA use driven by weight loss indications."},{"rthcId":"RPEP-05359","title":"Neurokinins and their receptors in the rat trigeminal system: Differential localization and release with implications for migraine pain.","authors":"Edvinsson, Jacob Ca; Reducha, Philip V; Sheykhzade, Majid; Warfvinge, Karin; Haanes, Kristian A; Edvinsson, Lars","year":2021,"journal":"Molecular pain, 17, 17448069211059400","doi":"10.1177/17448069211059400","pmid":"34898306","tags":["neuropeptides","pain"],"studyType":"animal (in vitro + immunohistochemistry)","evidenceStrength":"moderate","keyFinding":"Substance P release from stimulated dura mater, trigeminal ganglion neurons, and fibers was comparatively minor compared to CGRP release, explaining the clinical failure of NK1R antagonists for migraine while validating CGRP as the primary target.","whyItMatters":"This resolves a decades-old mystery in migraine research: why blocking substance P didn't work. It validates the scientific rationale behind current anti-CGRP migraine drugs and clarifies substance P's limited role in migraine pain.","specificNumbers":"SP co-localizes with CGRP in C-fibers; SP release minor vs CGRP from dura, TG, and fibers; NKA in some C-fibers; NKB in large/medium neurons and A-delta fibers","methodology":"Animal study using immunohistochemistry and semi-quantitative cell counts in rat trigeminal ganglia. Functional neuropeptide release measured by ELISA after stimulation with 60 mM potassium or 100 nM capsaicin.","limitations":"Rat model — human trigeminal physiology may differ. In vitro stimulation conditions may not replicate natural migraine triggers. Release measurements are relative comparisons, not absolute quantification."},{"rthcId":"RPEP-05360","title":"Spray-Dried Inhalable Powder Formulations of Therapeutic Proteins and Peptides.","authors":"Eedara, Basanth Babu; Alabsi, Wafaa; Encinas-Basurto, David; Polt, Robin; Mansour, Heidi M","year":2021,"journal":"AAPS PharmSciTech, 22(5), 185","doi":"10.1208/s12249-021-02043-5","pmid":"34143327","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05361","title":"Scorpion-Derived Antiviral Peptides with a Special Focus on Medically Important Viruses: An Update.","authors":"El Hidan, Moulay Abdelmonaim; Laaradia, Mehdi Ait; El Hiba, Omar; Draoui, Ahmed; Aimrane, Abdelmohcine; Kahime, Kholoud","year":2021,"journal":"BioMed research international, 2021, 9998420","doi":"10.1155/2021/9998420","pmid":"34527748","tags":["venom-peptides","antimicrobial-peptides","infection"],"studyType":"review","evidenceStrength":"n/a (review)","keyFinding":"Multiple scorpion venom peptides have demonstrated antiviral activity against several viral families, with potential biomedical applications against HIV, hepatitis, and coronaviruses.","whyItMatters":"With viral pandemics remaining a global threat, scorpion venom peptides represent an underexplored source of antiviral compounds that could lead to new treatments, especially as antibiotic resistance grows.","specificNumbers":"Active against HIV-1, HCV, HSV-1, measles virus, coronaviruses; mechanisms include membrane disruption, entry blocking, replication interference","methodology":"Narrative review of published literature on scorpion-derived antiviral peptides, their mechanisms of action, and potential biomedical applications.","limitations":"Review article with no new data. Most antiviral testing has been in vitro only. Scorpion peptide stability, toxicity, and delivery remain significant challenges for clinical development."},{"rthcId":"RPEP-05362","title":"De novo expression and antibacterial potential of four lactoferricin peptides in cell-free protein synthesis system.","authors":"El-Baky, Nawal Abd; Elkhawaga, Maie Ahmed; Abdelkhalek, Eman Shawky; Sharaf, Mona Mohammed; Redwan, Elrashdy Mustafa; Kholef, Hoda Reda","year":2021,"journal":"Biotechnology reports (Amsterdam, Netherlands), 29, e00583","doi":"10.1016/j.btre.2020.e00583","pmid":"33425692","tags":["antimicrobial-peptides","infection","peptide-design"],"studyType":"in vitro","evidenceStrength":"low","keyFinding":"Four lactoferricin peptides (bovine, human, camel, and synthetic consensus) showed antibacterial activity at MIC values of 1.25-10 μg/mL against E. coli, Salmonella typhi, Pseudomonas aeruginosa, S. aureus, and MRSA. Camel and consensus peptides were most potent.","whyItMatters":"With antibiotic resistance threatening global health, lactoferricin peptides effective against MRSA at low doses represent a promising class of alternative antimicrobials. The cell-free production method could accelerate development and testing of new peptide antibiotics.","specificNumbers":"4 peptides; MIC 1.25-10 micrograms/mL; cLFcin and ConLFcin most potent; first cell-free production of lactoferricin","methodology":"In vitro study. Four lactoferricin genes cloned into expression vector and synthesized using E. coli cell-free protein synthesis system. Antibacterial activity tested against 5 bacterial species including MRSA using minimum inhibitory concentration assays.","limitations":"In vitro testing only — no animal or human data. Peptide stability, toxicity to human cells, and in vivo efficacy were not assessed. Cell-free synthesis yields may not be sufficient for large-scale production."},{"rthcId":"RPEP-05363","title":"Activity of Anti-Microbial Peptides (AMPs) against Leishmania and Other Parasites: An Overview.","authors":"El-Dirany, Rima; Shahrour, Hawraa; Dirany, Zeinab; Abdel-Sater, Fadi; Gonzalez-Gaitano, Gustavo; Brandenburg, Klaus; Martinez de Tejada, Guillermo; Nguewa, Paul A","year":2021,"journal":"Biomolecules, 11(7)","doi":"10.3390/biom11070984","pmid":"34356608","tags":["antimicrobial-peptides","infection","immune-function"],"studyType":"review","evidenceStrength":"n/a (review)","keyFinding":"Nine AMP families (melittin, cecropin, cathelicidin, defensin, magainin, temporin, dermaseptin, eumenitin, histatin) demonstrate anti-leishmanial activity through direct lysis and immune modulation, offering alternatives to drug-resistant conventional treatments.","whyItMatters":"Leishmaniasis affects millions in tropical regions and current drugs are increasingly failing due to resistance. AMPs with dual-action mechanisms (direct killing + immune boosting) could provide much-needed new treatment options.","specificNumbers":"9 AMP families; mechanisms: membrane lysis and immune modulation; leishmaniasis is #2 parasitic disease after malaria","methodology":"Narrative review of published literature on antimicrobial peptide activity against Leishmania and other parasites, covering mechanisms of action, major peptide families, and therapeutic potential.","limitations":"Review of mostly preclinical data. AMP stability, toxicity, production costs, and delivery challenges remain significant barriers to clinical use. Most anti-leishmanial testing has been in vitro."},{"rthcId":"RPEP-05364","title":"DNA and modified vaccinia Ankara prime-boost vaccination generates strong CD8+ T cell responses against minor histocompatibility antigen HA-1.","authors":"Eldershaw, Suzy A; Pearce, Hayden; Inman, Charlotte F; Piper, Karen P; Abbotts, Ben; Stephens, Christine; Nicol, Samantha; Croft, Wayne; Powell, Richard; Begum, Jusnara; Taylor, Graham; Nunnick, Jane; Walsh, Donna; Sirovica, Mirjana; Saddique, Shamyla; Nagra, Sandeep; Ferguson, Paul; Moss, Paul; Malladi, Ram","year":2021,"journal":"British journal of haematology, 195(3), 433-446","doi":"10.1111/bjh.17495","pmid":"34046897","tags":["cancer","immune-function","peptide-design","clinical-trials"],"studyType":"clinical trial (phase I)","evidenceStrength":"low","keyFinding":"Seven of nine donors developed HA-1-specific CD8+ T cell responses up to 1.5% of total CD8+ repertoire after DNA-MVA prime-boost vaccination, with strong cytotoxic activity and responses detectable at 12 months.","whyItMatters":"Boosting anti-leukemia immune responses through vaccination could reduce relapse after stem cell transplant, which currently occurs in many patients despite otherwise successful transplantation.","specificNumbers":"9 donors; 7 responders; up to 1.5% of CD8+ repertoire; >12 month responses; TRBV7-9 TCR conservation; strong cytotoxic activity against HA-1-expressing targets","methodology":"Phase I clinical study. Nine HA-1-negative donors received 2-3 DNA priming vaccinations followed by modified vaccinia Ankara (MVA) boost. T cell responses measured by flow cytometry, cytotoxicity assays, and TCR repertoire analysis over 12 months.","limitations":"Small study (9 donors). Vaccination was in healthy donors, not leukemia patients. Clinical anti-leukemia efficacy not tested. The approach requires HLA-matched donors who are HA-1 negative, limiting the eligible population."},{"rthcId":"RPEP-05365","title":"A Hyaluronic Acid Demilune Scaffold and Polypyrrole-Coated Fibers Carrying Embedded Human Neural Precursor Cells and Curcumin for Surface Capping of Spinal Cord Injuries.","authors":"Elkhenany, Hoda; Bonilla, Pablo; Giraldo, Esther; Alastrue Agudo, Ana; Edel, Michael J; Vicent, María Jesus; Roca, Fernando Gisbert; Ramos, Cristina Martínez; Doblado, Laura Rodríguez; Pradas, Manuel Monleón; Manzano, Victoria Moreno","year":2021,"journal":"Biomedicines, 9(12)","doi":"10.3390/biomedicines9121928","pmid":"34944744","tags":["peptide-design","peptide-delivery","neuroprotection","wound-healing"],"studyType":"animal","evidenceStrength":"low","keyFinding":"Combination therapy using PuraMatrix peptide hydrogel, human neural progenitor cells, and nano-curcumin within a hyaluronic acid scaffold significantly increased neuro-preservation (βIII-tubulin staining) and decreased injured area (GFAP staining) after traumatic spinal cord contusion in rats.","whyItMatters":"Spinal cord injuries currently have no cure. This peptide-based scaffold approach offers a minimally invasive way to deliver stem cells and protective molecules directly to the injury site, showing real nerve preservation in animal testing.","specificNumbers":"Increased betaIII-tubulin staining; decreased injury area; reduced PDGF expression; curcumin reduced apoptosis and enhanced Nestin+ neurite outgrowth","methodology":"In vitro and in vivo study. PuraMatrix peptide hydrogel used to embed human induced neural progenitor cells with nano-curcumin in a hyaluronic acid scaffold with polypyrrole-coated fibers. Tested in spinal cord organotypic cultures and sub-acute traumatic contusion model in rats.","limitations":"Animal model (rats) with sub-acute injury timing. Functional recovery (movement, sensation) was not directly measured. Long-term outcomes unknown. Translation to human spinal cord injuries faces significant challenges in scale and complexity."},{"rthcId":"RPEP-05366","title":"Delivery of the VIVIT Peptide to Human Glioma Cells to Interfere with Calcineurin-NFAT Signaling.","authors":"Ellert-Miklaszewska, Aleksandra; Szymczyk, Agata; Poleszak, Katarzyna; Kaminska, Bozena","year":2021,"journal":"Molecules (Basel, Switzerland), 26(16)","doi":"10.3390/molecules26164785","pmid":"34443374","tags":["cancer","cell-penetrating","receptor-signaling","peptide-delivery"],"studyType":"in vitro","evidenceStrength":"low","keyFinding":"VIVIT-GFP overexpression successfully inhibited NFAT signaling in glioma cells, but neither Sim2-VIVIT nor 11R-VIVIT cell-penetrating peptide conjugates could reproduce this effect, indicating CPP delivery is insufficient for NFATc3-expressing gliomas.","whyItMatters":"This study reveals an important limitation of cell-penetrating peptide drug delivery: even when a peptide works inside cells, getting enough of it there via CPPs may not be sufficient. For glioma, dual-specificity blocking peptides may be needed.","specificNumbers":"VIVIT-GFP decreased NFAT activity and endogenous target genes; Sim-2-VIVIT: no activity; 11R-VIVIT: no NFAT inhibition; NFATc3 has 2 calcineurin docking sites","methodology":"In vitro study in human glioma cell lines. VIVIT expressed as GFP fusion protein (intracellular) or conjugated to CPPs Sim-2 and 11R (extracellular delivery). NFAT expression, phosphorylation, localization, and transcriptional activity measured.","limitations":"In vitro only with glioma cell lines. The negative CPP result may be specific to these peptide-target combinations. Alternative CPPs or delivery methods were not tested. Dosing and timing optimization may have been insufficient."},{"rthcId":"RPEP-05367","title":"Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2·4 mg for weight management: a randomised, controlled, phase 1b trial.","authors":"Enebo, Lone B; Berthelsen, Kasper K; Kankam, Martin; Lund, Michael T; Rubino, Domenica M; Satylganova, Altynai; Lau, David C W","year":2021,"journal":"Lancet (London, England), 397(10286), 1736-1748","doi":"10.1016/S0140-6736(21)00845-X","pmid":"33894838","tags":["next-gen-agonists","semaglutide","weight-loss","clinical-trials"],"studyType":"randomized controlled trial (phase 1b)","evidenceStrength":"moderate","keyFinding":"Cagrilintide 2.4 mg plus semaglutide 2.4 mg achieved 17.1% body weight reduction at 20 weeks, with an estimated treatment difference of -7.4% versus semaglutide plus placebo (95% CI -11.2 to -3.5). No pharmacokinetic interactions between the drugs.","whyItMatters":"This trial established that combining two appetite-regulating peptide hormones is safe and produces substantially greater weight loss than either alone, laying the groundwork for CagriSema as a next-generation obesity treatment.","specificNumbers":"96 randomized; 17.1% weight loss at cagrilintide 2.4mg; 15.7% at 1.2mg; 15.4% at 4.5mg; 9.8% placebo; treatment difference -7.4%; 37% GI AEs; cagrilintide t1/2 159-195h; semaglutide t1/2 145-165h","methodology":"Randomized, double-blind, placebo-controlled, multiple-ascending dose Phase 1b trial. Six sequential cohorts at a single US center. 96 randomized (95 treated). Cagrilintide 0.16-4.5 mg or placebo co-escalated with semaglutide 2.4 mg over 16 weeks, target dose maintained 4 weeks, 5-week follow-up.","limitations":"Small Phase 1b trial (96 participants) designed primarily for safety, not efficacy. Only 20 weeks of treatment — insufficient to assess long-term weight loss plateau. No lifestyle intervention included. Participants were otherwise healthy, so results may differ in people with obesity-related conditions."},{"rthcId":"RPEP-05368","title":"The Role of Endogenous Antimicrobial Peptides in Modulating Innate Immunity of the Ocular Surface in Dry Eye Diseases.","authors":"Eshac, Youssof; Redfern, Rachel L; Aakalu, Vinay Kumar","year":2021,"journal":"International journal of molecular sciences, 22(2)","doi":"10.3390/ijms22020721","pmid":"33450870","tags":["antimicrobial-peptides","immune-function","eye-health","inflammation"],"studyType":"review","evidenceStrength":"n/a (review)","keyFinding":"Antimicrobial peptides on the ocular surface serve multiple functions including microbial defense, wound healing, and immune modulation, and their homeostasis is disrupted in dry eye disease states.","whyItMatters":"Dry eye affects millions of people and current treatments are limited. Understanding AMPs' protective roles could lead to peptide-based eye drops or therapies that address the root immune dysfunction, not just symptoms.","specificNumbers":"AMPs: defensins, cathelicidins; roles: antimicrobial, wound healing, immune modulation; altered in dry eye","methodology":"Narrative review of published literature on antimicrobial peptides in ocular surface health and dry eye diseases.","limitations":"Narrative review with no new experimental data. Most AMP research in dry eye is preclinical. Clinical translation of peptide-based eye treatments faces stability and delivery challenges."},{"rthcId":"RPEP-05369","title":"Substance P and Neurokinin 1 Receptor in Chronic Inflammation and Cancer of the Head and Neck: A Review of the Literature.","authors":"Esteban, Francisco; Ramos-García, Pablo; Muñoz, Miguel; González-Moles, Miguel Ángel","year":2021,"journal":"International journal of environmental research and public health, 19(1)","doi":"10.3390/ijerph19010375","pmid":"35010633","tags":["neuropeptides","cancer","inflammation"],"studyType":"review","evidenceStrength":"n/a (review)","keyFinding":"Substance P and NK1R upregulate cell proliferation, cell migration, and chronic inflammation in head and neck cancers, playing a role in the transition from chronic mucosal inflammation to neoplastic transformation and progression.","whyItMatters":"If substance P drives the inflammatory-to-cancer transition in the head and neck, NK1R antagonists (substance P blockers) could potentially prevent or treat these cancers — a completely new therapeutic approach.","specificNumbers":"~1.5 million new cases/year; ~500,000 deaths/year; SP/NK1R upregulates proliferation, migration, inflammation; relevant to laryngeal and oral squamous cell carcinomas","methodology":"Narrative review of published literature on the substance P/NK1R system in chronic inflammation and carcinogenesis of the head and neck region.","limitations":"Narrative review with no new experimental data. Direct causal evidence for SP driving cancer in humans is limited. NK1R antagonists have not been tested as anticancer agents in head and neck cancer clinical trials."},{"rthcId":"RPEP-05370","title":"Thymosin beta-4 prenatal administration improves fetal development and halts side effects due to preterm delivery.","authors":"Faa, G; Piras, M; Mancuso, L; Coni, P; Pichiri, G; Orrù, G; Fanni, D; Gerosa, C; Cao, G; Taibi, R; Pavone, P; Castagnola, M","year":2021,"journal":"European review for medical and pharmacological sciences, 25(1), 431-437","doi":"10.26355/eurrev_202101_24411","pmid":"33506933","tags":["thymosin-beta-4","wound-healing","fertility"],"studyType":"animal","evidenceStrength":"low","keyFinding":"Maternal TB4 treatment (6 mg/kg on days E14 and E17) increased newborn cranio-caudal length and accelerated development of lungs, heart, kidneys, cerebral cortex, and notochord compared to control newborns.","whyItMatters":"Preterm birth is a leading cause of infant mortality, largely because organs haven't finished developing. If TB4 can accelerate organ maturation, it could help premature babies survive with fewer complications.","specificNumbers":"6 mice; TB4 6 mg/kg IP on E14 and E17; increased cranio-caudal length; advanced development of lungs, heart, kidney, cerebral cortex, notochord","methodology":"Animal study. 6 pregnant mice received intraperitoneal TB4 injections (6 mg/kg in PBS) on gestational days E14 and E17. Newborns assessed for body length and organ development by histology.","limitations":"Very small animal study (6 pregnant mice). No functional assessments of organ maturity. Long-term effects on offspring not evaluated. Mouse development may not directly translate to human pregnancy."},{"rthcId":"RPEP-05371","title":"Associations of early childhood caries with salivary beta defensin-3 and childhood anemia: a case-control study.","authors":"Faheem, Sanam; Maqsood, Shahida; Hasan, Arshad; Imtiaz, Fouzia; Shaikh, Faheem; Farooqui, Waqas Ahmed","year":2021,"journal":"BMC oral health, 21(1), 445","doi":"10.1186/s12903-021-01810-x","pmid":"34521396","tags":["antimicrobial-peptides","immune-function"],"studyType":"case-control","evidenceStrength":"low","keyFinding":"Salivary HBD-3 was inversely correlated with anemia (r=-0.479, p=0.002). Children with caries and anemia had the lowest HBD-3 levels (6.94 μg/L) versus caries without anemia (10.80 μg/L, p=0.001), suggesting anemia impairs innate antimicrobial peptide defense.","whyItMatters":"Anemia affects millions of children worldwide. Understanding that it impairs antimicrobial peptide defenses — not just iron — explains why anemic children are more susceptible to tooth decay and points to potential interventions.","specificNumbers":"HBD-3 caries: 8.87±4.30 vs controls: 7.23±2.57 (p=0.042); caries+no anemia: 10.80±4.50; caries+anemia: 6.94±3.13 (p=0.001); r=-0.479 for anemia-HBD3","methodology":"Case-control study of 80 hospitalized children (48-71 months). 40 with early childhood caries, 40 without. Sub-grouped by anemia status. Salivary HBD-3 measured by ELISA. Statistics: t-test, ANOVA, Spearman correlation.","limitations":"Small sample (80 children). Hospital-based sample may not represent general population. Cross-sectional design cannot establish causation. Salivary HBD-3 is just one component of oral defense."},{"rthcId":"RPEP-05372","title":"Prescribing in Type 2 Diabetes Patients With and Without Cardiovascular Disease History: A Descriptive Analysis in the UK CPRD.","authors":"Farmer, Ruth E; Beard, Ivan; Raza, Syed I; Gollop, Nicholas D; Patel, Niraj; Tebboth, Abigail; McGovern, Andrew P; Kanumilli, Naresh; Ternouth, Andrew","year":2021,"journal":"Clinical therapeutics, 43(2), 320-335","doi":"10.1016/j.clinthera.2020.12.015","pmid":"33581878","tags":["glp-1","diabetes","cardiovascular","regulatory"],"studyType":"observational (cross-sectional)","evidenceStrength":"moderate","keyFinding":"GLP-1RA use was only 4.3-4.9% and SGLT2i use 9.8-13.8% in UK T2DM patients by December 2019, with paradoxically lower use in patients with CVD history who would benefit most. Insulin use was 16% in CVD patients despite no cardiovascular evidence.","whyItMatters":"Heart disease is the leading killer of diabetes patients. Drugs proven to prevent cardiovascular events are being dramatically underused in the patients who need them most, while drugs without heart benefits are widely prescribed.","specificNumbers":"31% with CVD; SGLT2i: 9.8% (CVD) vs 13.8% (no CVD); GLP-1RA: 4.3% vs 4.9%; insulin: 16% vs 9.7%; SGLT2i as triple therapy rose from 22.7% to 41.3% (CVD) 2017-2019","methodology":"Descriptive cross-sectional analysis using UK Clinical Practice Research Datalink (CPRD). Four time points (2017-2019). 143,373-166,012 patients per cross-section. Age-standardized prescribing proportions by CVD history, treatment line, and UK country.","limitations":"UK-specific data that may not generalize to other healthcare systems. Cross-sectional design cannot determine reasons for prescribing decisions. Data ends at 2019 — GLP-1 prescribing has increased substantially since. Does not capture patient preferences or contraindications."},{"rthcId":"RPEP-05373","title":"epitopepredict: a tool for integrated MHC binding prediction.","authors":"Farrell, Damien","year":2021,"journal":"GigaByte (Hong Kong, China), 2021, gigabyte13","doi":"10.46471/gigabyte.13","pmid":"36824339","tags":[],"studyType":"Computational Tool/Software","evidenceStrength":"Preliminary","keyFinding":"The authors developed epitopepredict, an open-source computational tool that integrates multiple algorithms for predicting which peptide fragments will bind to MHC molecules — a critical step in designing vaccines and immunodiagnostics. The tool provides a unified interface for running several binding prediction methods, can screen entire microbial proteomes across multiple MHC alleles, and includes a web interface for visualizing and filtering results.","whyItMatters":"Identifying which peptides trigger an immune response is essential for vaccine development, but testing every possible peptide fragment in the lab is impractical. Computational screening narrows down candidates before expensive experiments begin. By combining multiple prediction algorithms into one accessible tool, epitopepredict makes this screening process faster and more accessible to researchers who may not be computational specialists.","specificNumbers":"Multiple binding prediction algorithms · Whole-proteome screening capability · Multiple MHC allele support · Open-source under free license","methodology":"The authors built a Python-based framework and command-line tool that wraps multiple established MHC binding prediction algorithms under a single interface. The tool is designed to scale from individual peptide queries to whole-genome proteome screening across multiple MHC alleles. A web-based visualization interface was also developed for filtering and interpreting results.","limitations":"This is a software description paper, not a validation study. No benchmarking data comparing epitopepredict's accuracy against existing tools is presented in the abstract. The tool's predictive accuracy depends entirely on the underlying algorithms it wraps. Computational predictions still require experimental validation before any clinical application."},{"rthcId":"RPEP-05374","title":"A randomized controlled trial of intranasal oxytocin in Phelan-McDermid syndrome.","authors":"Fastman, J; Foss-Feig, J; Frank, Y; Halpern, D; Harony-Nicolas, H; Layton, C; Sandin, S; Siper, P; Tang, L; Trelles, P; Zweifach, J; Buxbaum, J D; Kolevzon, A","year":2021,"journal":"Molecular autism, 12(1), 62","doi":"10.1186/s13229-021-00459-1","pmid":"34593045","tags":["oxytocin","neuroprotection","clinical-trials"],"studyType":"randomized controlled trial","evidenceStrength":"moderate","keyFinding":"Intranasal oxytocin showed no statistically significant improvement on social withdrawal (ABC-SW, p=0.055) or any secondary outcome in 18 children with PMS over 12 weeks.","whyItMatters":"Despite promising animal data, oxytocin did not help children with this genetic form of autism. This tempers expectations for oxytocin as an autism treatment.","specificNumbers":"18 children; ABC-SW p=0.055; 12-week double-blind + 12-week open-label; no significant secondary outcomes; no serious AEs","methodology":"Randomized, double-blind, placebo-controlled, parallel group trial with 12-week open-label extension. 18 children aged 5-17. Primary outcome: ABC-SW subscale.","limitations":"Very small sample (18 children). Drug administration challenges in young children. Parent-reported outcomes may have expectancy bias. Underpowered to detect small effects."},{"rthcId":"RPEP-05375","title":"Blocking NK1 receptors disrupts the sequential and temporal organization of chain grooming in rats.","authors":"Favila, Natalia; Gurney, Kevin; Overton, Paul G","year":2021,"journal":"Neuropharmacology, 196, 108716","doi":"10.1016/j.neuropharm.2021.108716","pmid":"34273385","tags":["neuropeptides","receptor-signaling"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"NK1 receptor antagonist L-733,060 made grooming chain transitions significantly more variable, simplified grooming bout structure, and increased transitions from active to inactive states — indicating substance P is critical for sequential action implementation.","whyItMatters":"Movement sequencing disorders (like those in Parkinson's and Huntington's disease) affect millions. Understanding that substance P helps the brain organize sequential actions could lead to new therapeutic approaches for these conditions.","specificNumbers":"L-733,060 at 2 and 4 mg/kg; more variable transitions; simpler bout structure; increased active-to-inactive transitions; Markov model and entropy analysis","methodology":"Within-subject counterbalanced design in rats. NK1R antagonist L-733,060 injected intraperitoneally at 2 and 4 mg/kg. Grooming sequences analyzed using first-order transition probabilities, Variable Length Markov Models, entropy metrics, and T-pattern analysis.","limitations":"Animal study with a specific innate behavior (grooming). The NK1R antagonist was systemic, so effects may not be limited to basal ganglia. Grooming sequences may not fully represent complex voluntary movement patterns in humans."},{"rthcId":"RPEP-05376","title":"Accentuated early postprandial satiety in people with spinal cord injury versus able-bodied controls.","authors":"Fenton, Jordan M; King, James A; Hoekstra, Sven P; Willis, Scott A; Ogawa, Takahiro; Goosey-Tolfrey, Victoria L","year":2021,"journal":"Appetite, 167, 105628","doi":"10.1016/j.appet.2021.105628","pmid":"34389376","tags":["glp-1","weight-loss"],"studyType":"crossover study","evidenceStrength":"low","keyFinding":"SCI patients showed higher early postprandial fullness (d=0.83) and satisfaction (d=0.87), ate less at ad libitum meals (1,086 vs 1,713 kJ, d=1.00, p=0.020), but had no significant differences in GLP-1, PYY, or acylated ghrelin responses.","whyItMatters":"Obesity in SCI patients was assumed to partly involve impaired appetite regulation. This study shows appetite is actually enhanced, meaning obesity in SCI is driven primarily by reduced energy expenditure, not overeating — which changes how weight management should be approached.","specificNumbers":"12+12; fullness d=0.83; satisfaction d=0.87 (0-60 min); ad lib intake 1,086 vs 1,713 kJ (p=0.020); no hormone differences (PYY, GLP-1, ghrelin)","methodology":"Counterbalanced crossover study. 12 men with high-level SCI (≥T6) and 12 able-bodied controls consumed covert high-energy (2,513 kJ) and low-energy (1,008 kJ) preloads. Subjective appetite and ad libitum intake measured. Appetite hormones measured in high-energy trial.","limitations":"Small study (24 participants). Only men studied. High-level SCI (≥T6) only — results may differ for lower-level injuries. Single center. Appetite hormone measurements may not capture all relevant signals."},{"rthcId":"RPEP-05377","title":"Gastroenteropancreatic neuroendocrine neoplasms: A clinical snapshot.","authors":"Fernandez, Cornelius J; Agarwal, Mayuri; Pottakkat, Biju; Haroon, Nisha Nigil; George, Annu Susan; Pappachan, Joseph M","year":2021,"journal":"World journal of gastrointestinal surgery, 13(3), 231-255","doi":"10.4240/wjgs.v13.i3.231","pmid":"33796213","tags":["cancer","hormone-optimization","peptide-design"],"studyType":"review","evidenceStrength":"n/a (review)","keyFinding":"Peptide hormone biomarkers are central to NEN diagnosis, and somatostatin analogues are first-line medical therapy. NETest (measuring 51 marker genes) achieves 85-98% sensitivity and 93-97% specificity for detecting gastrointestinal NENs.","whyItMatters":"Neuroendocrine tumors are increasing in incidence and require peptide-based diagnostics and treatments. Understanding which hormones to measure and how somatostatin analogues work is essential for proper management.","specificNumbers":"NETest: 85-98% sensitivity, 93-97% specificity, 51 marker genes; biomarkers: insulin, glucagon, VIP, gastrin, somatostatin, 5-HIAA; somatostatin analogs first-line","methodology":"Narrative review of pathophysiology, diagnostic algorithms, and management of gastroenteropancreatic neuroendocrine neoplasms.","limitations":"Narrative review with no new data. NEN management is highly specialized and individualized. Some emerging biomarkers require further validation in large prospective studies."},{"rthcId":"RPEP-05378","title":"Cerebrolysin for stroke, neurodegeneration, and traumatic brain injury: review of the literature and outcomes.","authors":"Fiani, Brian; Covarrubias, Claudia; Wong, Amelia; Doan, Thao; Reardon, Taylor; Nikolaidis, Daniel; Sarno, Erika","year":2021,"journal":"Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 42(4), 1345-1353","doi":"10.1007/s10072-021-05089-2","pmid":"33515100","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05379","title":"Antibacterial Gel Coatings Inspired by the Cryptic Function of a Mussel Byssal Peptide.","authors":"Fichman, Galit; Andrews, Caroline; Patel, Nimit L; Schneider, Joel P","year":2021,"journal":"Advanced materials (Deerfield Beach, Fla.), 33(40), e2103677","doi":"10.1002/adma.202103677","pmid":"34423482","tags":["antimicrobial-peptides","peptide-design","infection","wound-healing"],"studyType":"in vitro + animal","evidenceStrength":"moderate","keyFinding":"A mussel foot protein-5 derived peptide has cryptic antibacterial activity. The resulting MIKA2 hydrogel kills drug-resistant Gram-positive bacteria via dual mechanisms (membrane disruption + H₂O₂ production) and inhibited titanium implant colonization in mice.","whyItMatters":"Implant-associated infections are a major surgical complication, especially with rising antibiotic resistance. A peptide gel that is both adhesive (sticks to implants) and antibacterial could prevent these infections without systemic antibiotics.","specificNumbers":"MIKA2 gel; dual mechanism: membrane disruption + H2O2; active against drug-resistant Gram-positive bacteria; prevented implant colonization in mice","methodology":"In vitro and in vivo study. Peptide derived from mussel foot protein-5. Self-assembling hydrogels designed and tested for mechanical adhesion, antibacterial activity, and mechanism of action. Implant colonization prevention tested on titanium implants in mice.","limitations":"Mouse model only. Long-term biocompatibility and stability of the gel coating not fully assessed. Activity primarily against Gram-positive bacteria — Gram-negative coverage not demonstrated. Manufacturing scalability unclear."},{"rthcId":"RPEP-05380","title":"Elevated serum levels of cathelicidin and β-defensin 2 are associated with basal cell carcinoma.","authors":"Fijałkowska, Marta; Kowalski, Marek; Koziej, Mateusz; Antoszewski, Bogusław","year":2021,"journal":"Central-European journal of immunology, 46(3), 360-364","doi":"10.5114/ceji.2021.109707","pmid":"34764808","tags":["ll-37","antimicrobial-peptides","cancer","skin-repair"],"studyType":"case-control","evidenceStrength":"low","keyFinding":"Cathelicidin was ~3x and HBD-2 was >6x higher in BCC patients (p<0.001). Cathelicidin >1,500 pg/mL: OR 9.9 for BCC. HBD-2 >1.2 ng/mL: OR 12.6 for BCC (p<0.001). Both showed high specificity for detecting BCC.","whyItMatters":"A simple blood test measuring antimicrobial peptide levels could potentially help detect basal cell carcinoma — the world's most common cancer — complementing visual skin examination, especially for lesions that are difficult to assess clinically.","specificNumbers":"Cathelicidin ~3x higher; HBD-2 ~6x higher; cathelicidin >1500 pg/mL: OR 9.9; HBD-2 >1.2 ng/mL: OR 12.6 (p<0.001); high specificity","methodology":"Case-control study. 49 BCC patients and 59 controls. Serum cathelicidin and HBD-1, HBD-2, HBD-3 measured. Logistic regression for diagnostic accuracy. Statistical analysis of group differences.","limitations":"Relatively small case-control study. Cathelicidin and defensins are elevated in many conditions (infections, inflammation), limiting specificity for BCC specifically. Cannot determine whether elevated AMPs are a cause or consequence of BCC. No longitudinal data."},{"rthcId":"RPEP-05381","title":"Utilisation of collagenolytic enzymes from sierra fish (Scomberomorus sierra) and jumbo squid (Dosidicus gigas) viscera to generate bioactive collagen hydrolysates from jumbo squid muscle.","authors":"Fimbres-Romero, Manuel de J; Cabrera-Chávez, Francisco; Ezquerra-Brauer, Josafat M; Márquez-Ríos, Enrique; Suárez-Jiménez, Guadalupe M; Del Toro-Sanchez, Carmen L; Ramírez-Torres, Giovanni Isaí; Torres-Arreola, Wilfrido","year":2021,"journal":"Journal of food science and technology, 58(7), 2725-2733","doi":"10.1007/s13197-020-04780-0","pmid":"34194108","tags":["collagen-peptides","bioactive-food-peptides","cardiovascular"],"studyType":"in vitro","evidenceStrength":"low","keyFinding":"Sierra fish enzyme-derived squid collagen hydrolysates achieved 82.28% ACE inhibition and 64% ABTS antioxidant activity, with 15.2% of peptides below 3 kDa versus 7.9% from squid enzyme hydrolysates.","whyItMatters":"High blood pressure affects over a billion people globally. Bioactive peptides from sustainable seafood waste could provide natural ACE inhibitors as supplements or functional food ingredients, reducing reliance on synthetic drugs.","specificNumbers":"Collagen yield 0.98 g/100g muscle; SFE 15.2% <3 kDa peptides; 82.28% ACE inhibition; 64% ABTS inhibition; SFE 40% higher specific activity","methodology":"In vitro study. Collagen extracted from jumbo squid arms (yield 0.98 g/100g). Hydrolyzed with crude collagenase extracts from jumbo squid hepatopancreas and sierra fish viscera. ACE inhibition and ABTS radical scavenging measured.","limitations":"In vitro testing only — ACE inhibition in a test tube doesn't guarantee blood pressure effects in the body. Peptides may be degraded during digestion. Specific peptide sequences not identified. No human or animal testing."},{"rthcId":"RPEP-05382","title":"Tuneable Hybrid Hydrogels via Complementary Self-Assembly of a Bioactive Peptide with a Robust Polysaccharide.","authors":"Firipis, Kate; Boyd-Moss, Mitchell; Long, Benjamin; Dekiwadia, Chaitali; Hoskin, William; Pirogova, Elena; Nisbet, David R; Kapsa, Robert M I; Quigley, Anita F; Williams, Richard J","year":2021,"journal":"ACS biomaterials science & engineering, 7(7), 3340-3350","doi":"10.1021/acsbiomaterials.1c00675","pmid":"34125518","tags":["peptide-design","peptide-delivery","wound-healing"],"studyType":"in vitro (materials science)","evidenceStrength":"low","keyFinding":"Fmoc-DIKVAV and Fmoc-FRGDF peptides combined with agarose form hybrid hydrogels with tunable structural morphology and reinforced mechanical properties at mid-range agarose concentrations, providing tissue-specific biomaterial design capability.","whyItMatters":"Different tissues need different scaffold properties. A tunable system that lets researchers dial in the right combination of bioactivity and stiffness could accelerate development of tissue-specific regenerative therapies.","specificNumbers":"Fmoc-DIKVAV (IKVAV motif) and Fmoc-FRGDF (RGD motif); peptide-dominated at low agarose; hybrid at mid-range; agarose-dominated at high concentration; reinforced mechanics","methodology":"In vitro biomaterials study. Self-assembling Fmoc-peptides presenting IKVAV (laminin-derived) and RGD (fibronectin-derived) bioactive sequences combined with agarose at various concentrations. Physical characterization of morphology and mechanical properties.","limitations":"Characterization study focused on material properties. No cell culture or biological response data presented. In vivo performance and degradation behavior not assessed."},{"rthcId":"RPEP-05383","title":"AM833 Is a Novel Agonist of Calcitonin Family G Protein-Coupled Receptors: Pharmacological Comparison with Six Selective and Nonselective Agonists.","authors":"Fletcher, Madeleine M; Keov, Peter; Truong, Tin T; Mennen, Grace; Hick, Caroline A; Zhao, Peishen; Furness, Sebastian G B; Kruse, Thomas; Clausen, Trine R; Wootten, Denise; Sexton, Patrick M","year":2021,"journal":"The Journal of pharmacology and experimental therapeutics, 377(3), 417-440","doi":"10.1124/jpet.121.000567","pmid":"33727283","tags":["next-gen-agonists","weight-loss","receptor-signaling"],"studyType":"in vitro (pharmacology)","evidenceStrength":"moderate","keyFinding":"AM833 (cagrilintide) is a nonselective agonist with a unique pharmacological profile across 25 endpoints of receptor binding, activation, and regulation compared to 5 other selective and nonselective AMYR/CTR agonists including pramlintide and salmon calcitonin.","whyItMatters":"Understanding why cagrilintide works better than selective agonists helps optimize next-generation obesity drugs. The nonselective receptor profile explains its additive effects when combined with GLP-1 drugs like semaglutide (CagriSema).","specificNumbers":"25 endpoints; 7 peptides compared; AM833 nonselective at AMYR + CTR; unique profile vs pramlintide (selective), salmon CT (nonselective), and 4 others","methodology":"In vitro pharmacological profiling. AM833 compared against AM1213, AM1784, pramlintide, salmon calcitonin, human calcitonin, and rat amylin across 25 endpoints measuring receptor binding, signaling activation, and receptor regulation at calcitonin and amylin receptor subtypes.","limitations":"In vitro receptor pharmacology study — does not directly measure weight loss or clinical outcomes. Receptor-level activity may not fully predict in vivo efficacy. Differences between cell-based assays and physiological conditions are possible."},{"rthcId":"RPEP-05384","title":"Treating cognitive impairment in schizophrenia with GLP-1RAs: an overview of their therapeutic potential.","authors":"Flintoff, Jonathan; Kesby, James P; Siskind, Dan; Burne, Thomas Hj","year":2021,"journal":"Expert opinion on investigational drugs, 30(8), 877-891","doi":"10.1080/13543784.2021.1951702","pmid":"34213981","tags":["glp-1","cognitive-enhancement","neuroprotection"],"studyType":"review","evidenceStrength":"n/a (review)","keyFinding":"Preclinical evidence supports GLP-1 receptor agonists as potential cognitive enhancers, with activity in brain regions involved in learning and memory, though clinical evidence in schizophrenia is still needed.","whyItMatters":"Cognitive impairment in schizophrenia has no approved treatment and is the biggest predictor of long-term disability. Repurposing GLP-1 drugs already proven safe for other conditions could fill this critical therapeutic gap.","specificNumbers":"~1% worldwide prevalence of schizophrenia; no approved cognitive treatments; GLP-1RAs improve memory, learning, neuroprotection in rodent models","methodology":"Narrative review of preclinical and early clinical literature on GLP-1RA effects on cognition, with focus on potential applications in schizophrenia.","limitations":"Review based primarily on preclinical (animal) evidence. Cognitive effects in animal models may not translate to human schizophrenia. Clinical trials specifically testing GLP-1RAs for schizophrenia cognition are limited."},{"rthcId":"RPEP-05385","title":"Self-assembly of bio-inspired heterochiral peptides.","authors":"Florio, Daniele; Di Natale, Concetta; Scognamiglio, Pasqualina Liana; Leone, Marilisa; La Manna, Sara; Di Somma, Sarah; Netti, Paolo Antonio; Malfitano, Anna Maria; Marasco, Daniela","year":2021,"journal":"Bioorganic chemistry, 114, 105047","doi":"10.1016/j.bioorg.2021.105047","pmid":"34098256","tags":["peptide-design","peptide-delivery"],"studyType":"in vitro","evidenceStrength":"low","keyFinding":"Systematic D-amino acid substitution in a hexapeptide amyloid sequence modulated self-assembly conformation, aggregation kinetics, and microstructure morphology while maintaining hydrogel formation and HeLa cell compatibility.","whyItMatters":"Designing biomaterials requires fine control over material properties. This chirality-based approach provides a simple, systematic way to tune peptide hydrogels for specific applications without changing the amino acid sequence.","specificNumbers":"6 D-scan variants of NPM1 hexapeptide (residues 268-273); all formed hydrogels; distinct conformational intermediates; HeLa cell compatible","methodology":"In vitro study. D-scan of a hexapeptide (NPM1 residues 268-273). Structural properties characterized by multiple biophysical techniques. Hydrogel morphology and conformational intermediates analyzed. Cell compatibility evaluated in HeLa cells.","limitations":"Basic materials characterization with HeLa cell line compatibility only. No in vivo testing. Specific applications (wound healing, drug delivery) not tested. The amyloid-derived sequence may have different behavior in physiological conditions."},{"rthcId":"RPEP-05386","title":"Asthma Exacerbations in Patients with Type 2 Diabetes and Asthma on Glucagon-like Peptide-1 Receptor Agonists.","authors":"Foer, Dinah; Beeler, Patrick E; Cui, Jing; Karlson, Elizabeth W; Bates, David W; Cahill, Katherine N","year":2021,"journal":"American journal of respiratory and critical care medicine, 203(7), 831-840","doi":"10.1164/rccm.202004-0993OC","pmid":"33052715","tags":["glp-1","respiratory","inflammation","diabetes"],"studyType":"retrospective cohort","evidenceStrength":"moderate","keyFinding":"GLP-1RA users had significantly fewer asthma exacerbations at 6 months compared to SGLT-2 inhibitors (IRR 2.98), DPP-4 inhibitors (IRR 2.45), sulfonylureas (IRR 1.83), and basal insulin (IRR 2.58), all with p<0.05.","whyItMatters":"Asthma affects 300+ million people globally, and those with metabolic conditions often have worse outcomes. GLP-1 drugs could provide dual benefit — treating diabetes while also reducing airway inflammation and asthma attacks.","specificNumbers":"448 GLP-1RA; IRR vs GLP-1RA: SGLT2i 2.98, DPP-4i 2.45, SU 1.83, insulin 2.58; asthma symptom visits also lower with GLP-1RA","methodology":"Retrospective cohort study using electronic health records (2000-2018). New users of GLP-1RA (n=448) compared to SGLT-2i (n=112), DPP-4i (n=435), sulfonylureas (n=2,253), and basal insulin (n=2,692). Propensity score adjustment. Zero-inflated Poisson regression with multiple covariates.","limitations":"Retrospective observational study — cannot prove causation. Potential unmeasured confounders. GLP-1RA users may be healthier at baseline despite propensity score adjustment. Single academic healthcare system. Short 6-month follow-up."},{"rthcId":"RPEP-05387","title":"Rapid Production of Multifunctional Self-Assembling Peptides for Incorporation and Visualization within Hydrogel Biomaterials.","authors":"Ford, Eden M; Kloxin, April M","year":2021,"journal":"ACS biomaterials science & engineering, 7(9), 4175-4195","doi":"10.1021/acsbiomaterials.1c00589","pmid":"34283566","tags":["collagen-peptides","peptide-design","peptide-delivery"],"studyType":"methods development","evidenceStrength":"low","keyFinding":"Three new methods (targeted dual coupling synthesis, heat/ion purification, orthogonal fluorescent labeling) enabled scalable production and visualization of multifunctional collagen mimetic peptides in hydrogels.","whyItMatters":"Scalable production of complex self-assembling peptides is essential for translating biomaterial research into real therapeutic products.","specificNumbers":"Targeted dual chemistry coupling; heat + ion displacement purification; orthogonal fluorescent labeling; confocal 3D visualization of fibrillar structures in hydrogels","methodology":"Microwave-assisted peptide synthesis optimization. Identified deletion-prone residues and applied dual chemistry couplings. Heat/ion displacement purification. Fluorescent labeling for confocal microscopy of fibrillar structures.","limitations":"Methods demonstrated for one class of peptides (collagen mimetics). May not apply to all assembling sequences. No biological testing reported."},{"rthcId":"RPEP-05388","title":"Proteomic analysis of Red Sea Conus taeniatus venom reveals potential biological applications.","authors":"Fouda, Maged M A; Abdel-Wahab, Mohammed; Mohammadien, Amal; Germoush, Mousa O; Sarhan, Moustafa","year":2021,"journal":"The journal of venomous animals and toxins including tropical diseases, 27, e20210023","doi":"10.1590/1678-9199-JVATITD-2021-0023","pmid":"34712278","tags":["venom-peptides","peptide-design","pain"],"studyType":"in vitro (proteomics)","evidenceStrength":"low","keyFinding":"153 conotoxin precursors from 23 superfamilies identified in C. taeniatus venom, with T, O1, M, and O2 superfamilies comprising 63.4% of total conotoxin diversity.","whyItMatters":"Each cone snail species has a unique venom profile. Cataloging understudied species expands the library of potential drug molecules, especially for pain and neurological conditions.","specificNumbers":"234 peptide fragments; 153 conotoxin precursors; 23 superfamilies; 84% proteins 500-4,000 Da; T 22.87%, O1 17.65%, M 13.1%, O2 9.8%; 48 non-conotoxin proteins","methodology":"Proteomic analysis using bioanalytical techniques including mass spectrometry. Classification of conotoxin precursors and non-conotoxin proteins.","limitations":"Proteomic characterization only. No functional testing of individual peptides. Activities assigned by sequence similarity, not experimental verification."},{"rthcId":"RPEP-05389","title":"Snake Venom Components: Tools and Cures to Target Cardiovascular Diseases.","authors":"Frangieh, Jacinthe; Rima, Mohamad; Fajloun, Ziad; Henrion, Daniel; Sabatier, Jean-Marc; Legros, Christian; Mattei, César","year":2021,"journal":"Molecules (Basel, Switzerland), 26(8)","doi":"10.3390/molecules26082223","pmid":"33921462","tags":["venom-peptides","natriuretic-peptides","cardiovascular"],"studyType":"review","evidenceStrength":"n/a (review)","keyFinding":"Snake venoms contain multiple cardiovascular-active peptide classes: PLA2, natriuretic peptides, bradykinin-potentiating peptides, CRISPs, disintegrins, fibrinolytic enzymes, and three-finger toxins, with mechanisms including vasorelaxation, anti-platelet activity, and cardioprotection.","whyItMatters":"Snake venom already gave us one of medicine's most important drug classes (ACE inhibitors). The remaining venom peptides represent a rich, largely untapped pipeline for new cardiovascular therapeutics.","specificNumbers":"7 molecule classes; effects: vasorelaxation, platelet inhibition, cardioprotection; captopril derived from BPPs","methodology":"Narrative review of snake venom components targeting the cardiovascular system, their molecular targets, and mechanisms of action.","limitations":"Narrative review with no new data. Most venom peptides discussed are in preclinical stages. Translation from venom components to stable, safe drugs remains challenging."},{"rthcId":"RPEP-05390","title":"Activating the Cpx response induces tolerance to antisense PNA delivered by an arginine-rich peptide in Escherichia coli.","authors":"Frimodt-Møller, Jakob; Koulouktsis, Andreas; Charbon, Godefroid; Otterlei, Marit; Nielsen, Peter E; Løbner-Olesen, Anders","year":2021,"journal":"Molecular therapy. Nucleic acids, 25, 444-454","doi":"10.1016/j.omtn.2021.06.009","pmid":"34484867","tags":["cell-penetrating","antimicrobial-peptides","infection"],"studyType":"in vitro (bacterial genetics)","evidenceStrength":"moderate","keyFinding":"E. coli resistance to CPP-delivered antimicrobials requires constitutive Cpx stress response activation (cpx*), which decreases cytoplasmic membrane potential and blocks energy-dependent uptake of arginine-rich CPP conjugates.","whyItMatters":"CPP-delivered antimicrobials are a promising strategy against antibiotic-resistant bacteria. Understanding how bacteria resist this approach is essential for designing CPP-based antibiotics that avoid resistance development.","specificNumbers":"Multiple genetic modifications required; cpx* reduces membrane potential; cross-resistance to aminoglycosides; resistance specific to CPP not PNA","methodology":"Bacterial genetics study. Resistance mutants selected against PNA-CPP conjugates in E. coli. Genetic characterization of resistance mechanisms. Cpx pathway analysis. Membrane potential measurements. Cross-resistance testing with aminoglycosides and other CPP conjugates.","limitations":"E. coli laboratory study — resistance mechanisms may differ in other bacteria. In vitro conditions may not reflect in vivo resistance development. Clinical significance of Cpx-mediated resistance is unknown."},{"rthcId":"RPEP-05391","title":"Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes.","authors":"Frías, Juan P; Davies, Melanie J; Rosenstock, Julio; Pérez Manghi, Federico C; Fernández Landó, Laura; Bergman, Brandon K; Liu, Bing; Cui, Xuewei; Brown, Katelyn","year":2021,"journal":"The New England journal of medicine, 385(6), 503-515","doi":"10.1056/NEJMoa2107519","pmid":"34170647","tags":["tirzepatide","semaglutide","diabetes","weight-loss","clinical-trials"],"studyType":"randomized controlled trial (phase 3)","evidenceStrength":"high","keyFinding":"Tirzepatide was noninferior and superior to semaglutide 1mg: HbA1c reductions of -2.01%, -2.24%, -2.30% (5/10/15mg) vs -1.86% semaglutide. Weight loss differences: -1.9, -3.6, -5.5 kg favoring tirzepatide (all p<0.001).","whyItMatters":"This is the first head-to-head Phase 3 trial showing a new diabetes drug is superior to semaglutide — the previous best-in-class. It established tirzepatide as the most effective injectable for type 2 diabetes.","specificNumbers":"1,879 patients; HbA1c: -2.01/-2.24/-2.30% vs -1.86%; weight: -1.9/-3.6/-5.5 kg more; nausea 17-22% vs 18%; hypoglycemia 0.2-1.7% vs 0.4%; serious AEs 5-7% vs 3%","methodology":"Open-label, 40-week, Phase 3 RCT (SURPASS-2). 1,879 patients randomized 1:1:1:1 to tirzepatide 5/10/15 mg or semaglutide 1 mg weekly. Primary endpoint: HbA1c change from baseline to 40 weeks. NCT03987919.","limitations":"Open-label design (not blinded). Semaglutide dose was 1 mg (not the higher 2.4 mg dose used for weight management). Eli Lilly-funded. 40-week duration — longer-term comparisons needed. Serious adverse events slightly higher with tirzepatide (5-7% vs 3%)."},{"rthcId":"RPEP-05392","title":"Oral inhalation for delivery of proteins and peptides to the lungs.","authors":"Fröhlich, Eleonore; Salar-Behzadi, Sharareh","year":2021,"journal":"European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 163, 198-211","doi":"10.1016/j.ejpb.2021.04.003","pmid":"33852968","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05393","title":"Effects of whey protein and dietary fiber intake on insulin sensitivity, body composition, energy expenditure, blood pressure, and appetite in subjects with abdominal obesity.","authors":"Fuglsang-Nielsen, Rasmus; Rakvaag, Elin; Langdahl, Bente; Knudsen, Knud Erik Bach; Hartmann, Bolette; Holst, Jens Juul; Hermansen, Kjeld; Gregersen, Søren","year":2021,"journal":"European journal of clinical nutrition, 75(4), 611-619","doi":"10.1038/s41430-020-00759-4","pmid":"32948867","tags":["bioactive-food-peptides","weight-loss","glp-1"],"studyType":"randomized controlled trial","evidenceStrength":"moderate","keyFinding":"Whey protein for 12 weeks reduced subjective hunger (p=0.02) and increased postprandial peptide YY response (with low fiber), but had no effect on insulin sensitivity, GLP-1, body composition, 24-hour blood pressure, or energy expenditure versus maltodextrin control.","whyItMatters":"Whey protein is widely promoted for weight management, but this rigorous trial shows its benefits may be limited to appetite reduction without meaningful metabolic improvements — important context for consumers spending money on protein supplements.","specificNumbers":"73 randomized; 60 g/day WP; 12 weeks; hunger p=0.02; PYY increased with WP+LoFi; no effects on GLP-1, GLP-2, GIP, insulin sensitivity, body composition, BP, or energy expenditure","methodology":"12-week, double-blind, randomized, controlled, parallel study. 73 subjects with abdominal obesity. 4 groups: whey protein hydrolysate (60g/day) or maltodextrin + high-fiber (30g/day) or low-fiber (10g/day). Assessed: insulin sensitivity, gut hormones (GLP-1, GLP-2, GIP, PYY), body composition, blood pressure, energy expenditure.","limitations":"Relatively small study (73 subjects, 65 completed). 12-week duration may be insufficient for body composition changes. 60g/day whey protein is a high dose. Maltodextrin control may have metabolic effects of its own. Population-specific (abdominal obesity)."},{"rthcId":"RPEP-05394","title":"Identification of two distinct populations of WT1-specific cytotoxic T lymphocytes in co-vaccination of WT1 killer and helper peptides.","authors":"Fujiki, Fumihiro; Tsuboi, Akihiro; Morimoto, Soyoko; Hashimoto, Naoya; Inatome, Miki; Nakajima, Hiroko; Nakata, Jun; Nishida, Sumiyuki; Hasegawa, Kana; Hosen, Naoki; Oka, Yoshihiro; Oji, Yusuke; Sogo, Shinji; Sugiyama, Haruo","year":2021,"journal":"Cancer immunology, immunotherapy : CII, 70(1), 253-263","doi":"10.1007/s00262-020-02675-9","pmid":"32696072","tags":["cancer","immune-function","peptide-design"],"studyType":"clinical (observational comparison)","evidenceStrength":"low","keyFinding":"WT1 CTL + helper peptide vaccine induced stronger WT1-specific CTL responses than CTL peptide alone in glioma patients, generating a novel WT1-tetramer-high CD5-high CTL population with enhanced persistence capacity.","whyItMatters":"Glioma (brain cancer) has very poor outcomes. This study shows that adding a helper peptide to cancer vaccines can dramatically improve immune responses, potentially improving survival — a principle applicable to many peptide-based cancer vaccines.","specificNumbers":"Two CTL populations; CD5-low (WT1-tetramer-low) and CD5-high (WT1-tetramer-high); CD5-high resistant to AICD; CTL-HTL response correlation; helper peptide enhanced CTL induction","methodology":"Clinical immunological study in patients with recurrent glioma. Compared WT1 CTL peptide alone versus WT1 CTL + WT1 helper peptide (WT1332) vaccination. T cell responses measured by tetramer staining, TCR expression, CD5 levels, and proliferation assays.","limitations":"Small clinical study in recurrent glioma patients. Immunological endpoints only — clinical survival benefit not directly demonstrated. Results may be specific to WT1 and this HLA context."},{"rthcId":"RPEP-05395","title":"CAPS2 Deficiency Impairs the Release of the Social Peptide Oxytocin, as Well as Oxytocin-Associated Social Behavior.","authors":"Fujima, Shuhei; Yamaga, Ryosuke; Minami, Haruka; Mizuno, Shota; Shinoda, Yo; Sadakata, Tetsushi; Abe, Manabu; Sakimura, Kenji; Sano, Yoshitake; Furuichi, Teiichi","year":2021,"journal":"The Journal of neuroscience : the official journal of the Society for Neuroscience, 41(20), 4524-4535","doi":"10.1523/JNEUROSCI.3240-20.2021","pmid":"33846232","tags":["oxytocin","neuropeptides","receptor-signaling"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"CAPS2 knockout mice had reduced plasma but increased hypothalamic/pituitary oxytocin levels (release failure). OXT neuron-specific CAPS2 deletion impaired social interaction and recognition, which was rescued by intranasal oxytocin administration.","whyItMatters":"Understanding how oxytocin release is regulated could lead to treatments for social behavior disorders including autism. If the problem is release rather than production, therapies could target the release mechanism or bypass it with exogenous oxytocin.","specificNumbers":"Reduced plasma OXT; increased hypothalamic/pituitary OXT; impaired social interaction and recognition; intranasal OXT rescue; CAPS2 expressed in hypothalamic OXT neurons","methodology":"Animal study. CAPS2 knockout and conditional knockout mice (OXT neuron-specific). Plasma and tissue oxytocin levels measured. Social behavior testing. Intranasal oxytocin rescue experiment. CAPS2 localization in hypothalamic OXT neurons and pituitary.","limitations":"Mouse model — social behavior in mice may not fully represent human social interaction. CAPS2 mutations are rare in autism. Intranasal oxytocin delivery to the brain in humans remains debated. Long-term effects of oxytocin rescue not assessed."},{"rthcId":"RPEP-05396","title":"Functional Peptides That Target Biomembranes: Design and Modes of Action.","authors":"Futaki, Shiroh","year":2021,"journal":"Chemical & pharmaceutical bulletin, 69(7), 601-607","doi":"10.1248/cpb.c21-00140","pmid":"34193708","tags":["cell-penetrating","peptide-design","peptide-delivery"],"studyType":"review","evidenceStrength":"n/a (review)","keyFinding":"Iterative peptide design yielded functional peptides with refined ability to modulate biomembrane barrier function, lipid packing, and structure.","whyItMatters":"Many diseases involve membrane dysfunction, and many drugs need to cross membranes. Peptides that precisely control membrane properties could improve drug delivery, fight infections, and potentially treat membrane-related diseases.","specificNumbers":"Peptides target membrane barrier function, lipid packing, and structure; iterative design approach","methodology":"Review of laboratory research on the design and evaluation of membrane-targeting functional peptides, including analysis of cellular mechanisms.","limitations":"Brief review focused on a single laboratory's work. Broad clinical applicability not demonstrated. In vivo translation of membrane-modulating peptides faces significant challenges."},{"rthcId":"RPEP-05397","title":"Harnessing the Anti-Nociceptive Potential of NK2 and NK3 Ligands in the Design of New Multifunctional μ/δ-Opioid Agonist-Neurokinin Antagonist Peptidomimetics.","authors":"Gadais, Charlène; Piekielna-Ciesielska, Justyna; De Neve, Jolien; Martin, Charlotte; Janecka, Anna; Ballet, Steven","year":2021,"journal":"Molecules (Basel, Switzerland), 26(17)","doi":"10.3390/molecules26175406","pmid":"34500841","tags":["opioid-peptides","neuropeptides","pain","peptide-design"],"studyType":"in vitro","evidenceStrength":"low","keyFinding":"Three hybrid compounds (SBL-OPNK-5, -7, -9) bearing the KGOP01 scaffold achieved nanomolar μ-opioid receptor affinity, slightly reduced δ-opioid receptor affinity, and (sub)nanomolar NK2 and NK3 binding — the first designed multi-ligands targeting these receptor combinations.","whyItMatters":"Multi-target peptide drugs could provide effective pain relief with fewer opioid side effects by simultaneously engaging pain-suppressing opioid pathways and blocking pain-amplifying neurokinin pathways.","specificNumbers":"3 successful hybrids (SBL-OPNK-5/7/9); nanomolar MOR affinity; (sub)nanomolar NK2/NK3; KGOP01 scaffold; first opioid-NK2/NK3 DMLs","methodology":"Medicinal chemistry study. Peptidic and pseudo-peptidic NK2/NK3 ligands covalently linked to opioid pharmacophores (Dmt-DALDA and KGOP01). Opioid and neurokinin receptor binding assays performed.","limitations":"Binding assays only — no functional activity, animal testing, or pain relief measurement. In vitro receptor binding may not predict in vivo efficacy. Peptide stability and bioavailability not assessed."},{"rthcId":"RPEP-05398","title":"Tryptophan Promotes Intestinal Immune Defense through Calcium-Sensing Receptor (CaSR)-Dependent Metabolic Pathways.","authors":"Gao, Nan; Dou, Xiujing; Yin, Ting; Yang, Yang; Yan, Di; Ma, Ziwen; Bi, Chongpeng; Shan, Anshan","year":2021,"journal":"Journal of agricultural and food chemistry, 69(45), 13460-13473","doi":"10.1021/acs.jafc.1c05820","pmid":"34748328","tags":["antimicrobial-peptides","gut-healing","immune-function","bioactive-food-peptides"],"studyType":"in vitro + animal","evidenceStrength":"moderate","keyFinding":"Tryptophan triggers defensin expression through CaSR activation, reduces LPS-induced IL-1β (75.26 pg/mL) and TNF-α (449.8 pg/mL) levels, and maintains kynurenine homeostasis through CaSR signaling during inflammatory responses.","whyItMatters":"This connects dietary nutrition directly to innate immune defense. Adequate tryptophan intake may help maintain gut antimicrobial peptide levels and reduce inflammation — relevant for anyone concerned about gut health and immune function.","specificNumbers":"Tryptophan activates CaSR; defensin expression increased; IL-1beta 75.26±2.74 pg/mL; TNF-alpha 449.8±23.31 pg/mL with CaSR activation; kynurenine homeostasis maintained","methodology":"In vitro and in vivo study. Tryptophan treatment of intestinal cells and animal models. CaSR signaling pathway analysis. Defensin expression measured. Inflammatory cytokines quantified. Kynurenine metabolic pathway assessed.","limitations":"Combination of in vitro and animal data. Human relevance needs confirmation. Tryptophan metabolism is complex and context-dependent. Optimal dietary tryptophan levels for immune benefit not determined."},{"rthcId":"RPEP-05399","title":"Rational design and chemical modification of TEAD coactivator peptides to target hippo signaling pathway against gastrointestinal cancers.","authors":"Gao, Shuxia; Wang, Yingchao; Ji, Lijuan","year":2021,"journal":"Journal of receptor and signal transduction research, 41(4), 408-415","doi":"10.1080/10799893.2020.1818093","pmid":"32912021","tags":["cyclic-peptides","peptide-design","cancer"],"studyType":"in vitro (computational + binding assays)","evidenceStrength":"low","keyFinding":"Rational design and all-hydrocarbon stapling of TEAD coactivator α-helix peptides improved binding affinity >5-fold by stabilizing helical structure (reducing indirect readout penalty) and optimizing interfacial residues (enhancing direct readout).","whyItMatters":"The Hippo pathway is dysregulated in many GI cancers but has been difficult to drug. Stapled peptides that block TEAD-coactivator interactions could fill this therapeutic gap, offering a new approach to hard-to-treat cancers.","specificNumbers":">5-fold affinity improvement; i to i+4 hydrocarbon staple; staple points outward; hydrogen bonds and hydrophobic contacts; alpha-helix and omega-loop hotspot sites","methodology":"Computational and experimental study. Rational peptide design, all-hydrocarbon i, i+4 stapling modification, structural analysis, and binding affinity assays for TEAD-peptide interactions.","limitations":"In vitro binding studies only. No cell-based or animal testing of anti-cancer activity. Stapled peptide delivery to intracellular targets in tumors remains a challenge. Cost of stapled peptide manufacturing."},{"rthcId":"RPEP-05400","title":"Coassembly Behavior and Rheological Properties of a β-Hairpin Peptide with Dicarboxylates.","authors":"Ge, Yanqing; Wang, Chen; Zhang, Weiqiang; Lai, Shike; Wang, Dong; Wang, Jiqian","year":2021,"journal":"Langmuir : the ACS journal of surfaces and colloids, 37(40), 11657-11664","doi":"10.1021/acs.langmuir.1c01376","pmid":"34597056","tags":["peptide-design","peptide-delivery"],"studyType":"in vitro","evidenceStrength":"low","keyFinding":"Beta-hairpin peptide CBHH co-assembled with succinic, malic, and tartaric dicarboxylates to form hydrogels with tunable rheological properties and cell culture compatibility, with molecular interactions characterized by CD and AFM.","whyItMatters":"Simple, tunable hydrogels from biocompatible components could provide practical scaffolds for tissue engineering, wound healing, and drug delivery applications.","specificNumbers":"3 dicarboxylates; gelation at low pH; hydroxyl group-dependent properties; MTT and Calcein-AM/PI confirmed biocompatibility","methodology":"In vitro study. Beta-hairpin peptide CBHH co-assembled with three dicarboxylates. Characterized by circular dichroism spectroscopy, atomic force microscopy, and rheology. Cell culture compatibility assessed.","limitations":"Basic characterization study. Specific tissue engineering or drug delivery applications not tested. Limited to one peptide sequence."},{"rthcId":"RPEP-05401","title":"Amylin Analog Pramlintide Induces Migraine-like Attacks in Patients.","authors":"Ghanizada, Hashmat; Al-Karagholi, Mohammad Al-Mahdi; Walker, Christopher S; Arngrim, Nanna; Rees, Tayla; Petersen, Jakeb; Siow, Andrew; Mørch-Rasmussen, Mette; Tan, Sheryl; O'Carroll, Simon J; Harris, Paul; Skovgaard, Lene Theil; Jørgensen, Niklas Rye; Brimble, Margaret; Waite, Jayme S; Rea, Brandon J; Sowers, Levi P; Russo, Andrew F; Hay, Debbie L; Ashina, Messoud","year":2021,"journal":"Annals of neurology, 89(6), 1157-1171","doi":"10.1002/ana.26072","pmid":"33772845","tags":["next-gen-agonists","neuropeptides","pain"],"studyType":"randomized controlled trial (crossover) + animal","evidenceStrength":"high","keyFinding":"Pramlintide induced headache in 88% and migraine-like attacks in 41% of patients (vs CGRP: 97% and 56%, differences not significant). The effects were mediated through amylin receptors, not the canonical CGRP receptor. Animal models confirmed amylin causes cutaneous hypersensitivity and light aversion.","whyItMatters":"Current anti-CGRP migraine drugs help many but not all patients. Identifying amylin receptor agonism as a novel migraine contributor suggests that blocking both amylin and CGRP receptors could help patients who don't respond to CGRP-targeting drugs alone.","specificNumbers":"36 patients; headache 88% vs 97%; migraine 41% vs 56% (p=0.180); amylin receptor mediated; mouse: cutaneous hypersensitivity and light aversion with both amylin and CGRP","methodology":"Randomized, double-blind, 2-way crossover clinical trial in 36 migraine without aura patients. Pramlintide or human αCGRP infusion on separate days. Supplemented with in vitro receptor pharmacology, mouse behavioral models, and tissue studies in rat, mouse, and human samples.","limitations":"Moderate sample size (36 patients). Migraine provocation models may not perfectly replicate spontaneous migraine. Pramlintide is designed for diabetes, not migraine — optimal amylin receptor manipulation for migraine needs development."},{"rthcId":"RPEP-05402","title":"Therapeutic Potential of a Novel Glucagon-like Peptide-1 Receptor Agonist, NLY01, in Experimental Autoimmune Encephalomyelitis.","authors":"Gharagozloo, Marjan; Smith, Matthew D; Sotirchos, Elias S; Jin, Jing; Meyers, Keya; Taylor, Michelle; Garton, Thomas; Bannon, Riley; Lord, Hannah-Noelle; Dawson, Ted M; Dawson, Valina L; Lee, Seulki; Calabresi, Peter A","year":2021,"journal":"Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 18(3), 1834-1848","doi":"10.1007/s13311-021-01088-5","pmid":"34260042","tags":["glp-1","neuroprotection","inflammation","immune-function"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"NLY01 delayed EAE onset and reduced severity in prevention paradigm, inhibited immune cell activation and CNS trafficking, suppressed chemokine production, blocked neurotoxic astrocyte genes, prevented retinal ganglion cell loss, and reduced clinical scores in relapsing-remitting EAE.","whyItMatters":"MS currently has no approved neuroprotective therapy. GLP-1 drugs that both suppress inflammation and protect neurons could fundamentally change MS treatment by addressing the component that causes permanent disability.","specificNumbers":"Delayed onset; reduced severity; suppressed splenic immune cells; reduced CNS trafficking; blocked neurotoxic astrocyte genes; prevented RGC loss; reduced relapse in RR-EAE","methodology":"Preclinical study. Mouse experimental autoimmune encephalomyelitis (EAE) model. Prevention and therapeutic paradigms tested. Immune cell analysis, chemokine profiling, gene expression in optic nerves, and retinal ganglion cell quantification.","limitations":"Mouse EAE model only — human MS is more complex. Prevention paradigm (pre-disease) is less clinically relevant than therapeutic paradigm. NLY01 has not been tested in MS patients. EAE models may not capture all aspects of progressive MS."},{"rthcId":"RPEP-05403","title":"New Perspectives in the Pathophysiology and Treatment of Pain in Patients with Dry Eye Disease.","authors":"Giannaccare, Giuseppe; Ghelardini, Carla; Mancini, Alessandra; Scorcia, Vincenzo; Di Cesare Mannelli, Lorenzo","year":2021,"journal":"Journal of clinical medicine, 11(1)","doi":"10.3390/jcm11010108","pmid":"35011849","tags":["opioid-peptides","pain","eye-health"],"studyType":"review","evidenceStrength":"n/a (review)","keyFinding":"Eye pain in dry eye disease is modulated by endogenous opioid peptides. Peripheral and central sensitization causes pain persistence. Topical opiorphin-containing formulations represent a novel theoretical approach to treat ocular pain by enhancing endogenous enkephalin activity.","whyItMatters":"Chronic eye pain affects millions of dry eye sufferers and is notoriously difficult to treat. Leveraging the eye's own opioid peptide system through topical formulations could provide a fundamentally new treatment approach without systemic opioid side effects.","specificNumbers":"Pain progression: peripheral then central sensitization; endogenous opioids: enkephalins, endorphins, dynorphins; novel: opiorphin-based protein-GAG complex topical agent","methodology":"Narrative review of pain pathophysiology in dry eye disease, focusing on peripheral and central sensitization mechanisms and the role of endogenous opioid peptides in ocular pain modulation.","limitations":"Review with theoretical therapeutic proposals. Opiorphin-based eye drops are not yet validated in clinical trials. Efficacy and safety of topical opioid peptide modulation in dry eye patients are unknown."},{"rthcId":"RPEP-05404","title":"Effects of oral semaglutide on energy intake, food preference, appetite, control of eating and body weight in subjects with type 2 diabetes.","authors":"Gibbons, Catherine; Blundell, John; Tetens Hoff, Søren; Dahl, Kirsten; Bauer, Robert; Baekdal, Tine","year":2021,"journal":"Diabetes, obesity & metabolism, 23(2), 581-588","doi":"10.1111/dom.14255","pmid":"33184979","tags":["semaglutide","weight-loss","diabetes","oral-peptides"],"studyType":"Randomized Controlled Trial","evidenceStrength":"Moderate","keyFinding":"Oral semaglutide 14mg reduced total daily ad libitum energy intake by 38.9% versus placebo (treatment difference -5,096 kJ, p=0.0001). Increased satiety and fullness after fat-rich breakfast. Body weight decreased 2.7 kg (mostly fat mass) vs 0.1 kg placebo.","whyItMatters":"Understanding exactly how GLP-1 drugs reduce food intake helps explain their weight loss effects and informs clinical use. The 39% calorie reduction explains the meaningful weight loss seen in larger trials.","specificNumbers":"38.9% energy intake reduction; 5,096 kJ/day difference; 2.7 kg weight loss vs 0.1 kg; P=0.0001","methodology":"Randomized, double-blind, placebo-controlled, two-period crossover trial. 15 subjects with T2D. 12 weeks oral semaglutide (escalated 3→7→14 mg) vs placebo. Ad libitum energy intake, appetite VAS ratings after standard and fat-rich breakfasts, Control of Eating Questionnaire, body composition.","limitations":"Very small study (15 subjects, 13 evaluable). Short duration (12 weeks). Crossover design in T2D patients — results may differ in non-diabetic obesity. Laboratory meal setting may not reflect real-world eating behavior."},{"rthcId":"RPEP-05405","title":"Age-Related Expression of IFN-λ1 Versus IFN-I and Beta-Defensins in the Nasopharynx of SARS-CoV-2-Infected Individuals.","authors":"Gilbert, Charly; Lefeuvre, Caroline; Preisser, Laurence; Pivert, Adeline; Soleti, Raffaella; Blanchard, Simon; Delneste, Yves; Ducancelle, Alexandra; Couez, Dominique; Jeannin, Pascale","year":2021,"journal":"Frontiers in immunology, 12, 750279","doi":"10.3389/fimmu.2021.750279","pmid":"34858406","tags":["antimicrobial-peptides","immune-function","infection"],"studyType":"Observational Study","evidenceStrength":"Moderate","keyFinding":"SARS-CoV-2 infection induced selective IFN-λ1 upregulation in children (≤15 years) without β-defensin changes, while adults (15-65) and elderly (≥65) showed IFN-α/β and β-defensin 1-3 upregulation without IFN-λ1 modulation. 226 subjects analyzed.","whyItMatters":"Understanding why children resist severe COVID-19 could inform treatments for adults. The finding that children use a different, more targeted innate immune response — and that defensin responses differ by age — has implications for future pandemic preparedness.","specificNumbers":"226 individuals; 3 age groups; IFN-lambda-1 selective in children under 15; beta-defensins 1-3 upregulated in adults/elderly only","methodology":"Cross-sectional study. Nasopharyngeal swabs from 226 individuals (children, adults, elderly; SARS-CoV-2 positive/negative). mRNA expression of type I/III interferons, β-defensins 1-3, α-defensins, LL-37, pentraxin-3, surfactant protein D, IL-26, IFITM1/3 measured.","limitations":"Cross-sectional design cannot establish causation. mRNA levels may not reflect protein levels. Nasopharyngeal samples represent local, not systemic immunity. Functional significance of the different defensin/interferon patterns needs direct testing."},{"rthcId":"RPEP-05406","title":"Synthesis and Pharmacological Characterization of Visabron, a Backbone Cyclic Peptide Dual Antagonist of α4β1 (VLA-4)/α9β1 Integrin for Therapy of Multiple Sclerosis.","authors":"Gilon, Chaim; Klazas, Michal; Lahiani, Adi; Schumacher-Klinger, Adi; Merzbach, Shira; Naoum, Johnny N; Ovadia, Haim; Rubin, Limor; Cornell-Kennon, Susan; Schaefer, Erik M; Katzhendler, Jehoshua; Marcinkiewicz, Cezary; Hoffman, Amnon; Lazarovici, Philip","year":2021,"journal":"JACS Au, 1(12), 2361-2376","doi":"10.1021/jacsau.1c00496","pmid":"34977904","tags":["cyclic-peptides","venom-peptides","inflammation","peptide-design"],"studyType":"Preclinical Animal Study","evidenceStrength":"Preliminary","keyFinding":"Visabron c(4-4), a backbone cyclic octapeptide derived from viper venom disintegrin, effectively reduced EAE disease severity in mice while showing no immunogenicity or off-target toxicity.","whyItMatters":"Natalizumab works well for MS but carries the risk of a serious brain infection (PML) with long-term use. A small peptide that does the same job without triggering immune reactions could be a safer alternative.","specificNumbers":"8-amino-acid cyclic peptide; dual alpha4beta1/alpha9beta1 antagonist; no immunogenicity; no off-target effects","methodology":"Peptide design and synthesis from a minilibrary with conformational diversity. Functional adhesion cellular assays for potency/selectivity. Serum stability and pharmacokinetics testing. In vivo efficacy in EAE mouse model (IP injection). Safety assessed via blood analysis, tissue pathology, immunogenicity, and off-target effects.","limitations":"Animal study only (mice with EAE, not humans with MS). EAE does not perfectly mirror human MS. Specific dosing and duration details limited. No head-to-head comparison with natalizumab in the same model. Long-term safety in animals not reported."},{"rthcId":"RPEP-05407","title":"Iron metabolism in infections: Focus on COVID-19.","authors":"Girelli, Domenico; Marchi, Giacomo; Busti, Fabiana; Vianello, Alice","year":2021,"journal":"Seminars in hematology, 58(3), 182-187","doi":"10.1053/j.seminhematol.2021.07.001","pmid":"34389110","tags":["antimicrobial-peptides","immune-function","infection"],"studyType":"Review","evidenceStrength":"Low","keyFinding":"Hepcidin, a defensin-related liver peptide, sequesters iron from pathogens during infection, and disruption of this system may contribute to COVID-19 severity.","whyItMatters":"Iron is not just a nutrient. The body actively uses it as a weapon against germs. Understanding this system could reveal new ways to treat infections, including COVID-19, by targeting iron pathways rather than the virus directly.","specificNumbers":"No original data; hepcidin structurally linked to defensins","methodology":"Narrative review of published literature on iron metabolism, hepcidin biology, and their intersection with SARS-CoV-2 infection and COVID-19 outcomes.","limitations":"Narrative review with no original data. COVID-19 implications are largely theoretical at this stage. Iron metabolism is complex and interventions could have unintended consequences."},{"rthcId":"RPEP-05408","title":"GLP-1 receptor agonists and cardiorenal outcomes in type 2 diabetes: an updated meta-analysis of eight CVOTs.","authors":"Giugliano, Dario; Scappaticcio, Lorenzo; Longo, Miriam; Caruso, Paola; Maiorino, Maria Ida; Bellastella, Giuseppe; Ceriello, Antonio; Chiodini, Paolo; Esposito, Katherine","year":2021,"journal":"Cardiovascular diabetology, 20(1), 189","doi":"10.1186/s12933-021-01366-8","pmid":"34526024","tags":["glp-1","cardiovascular","diabetes","kidney","clinical-trials"],"studyType":"Meta-Analysis","evidenceStrength":"Strong","keyFinding":"GLP-1 receptor agonists reduced MACE by 14% (HR 0.86), cardiovascular death by 13%, nonfatal stroke by 16%, heart failure hospitalization by 10%, all-cause mortality by 12%, and composite kidney outcome by 17%.","whyItMatters":"This is one of the most comprehensive analyses showing GLP-1 drugs do more than control blood sugar. They protect the heart, brain, and kidneys. This supports using these drugs not just for diabetes but for cardiovascular risk reduction.","specificNumbers":"60,080 patients; 8 CVOTs; HR 0.86 MACE; HR 0.87 CV death; HR 0.84 stroke; HR 0.90 HF hospitalization; HR 0.88 all-cause mortality; HR 0.83 kidney composite","methodology":"Systematic review and meta-analysis using random-effects model. Electronic search up to June 2021. Included 8 cardiovascular outcome trials (CVOTs) with 60,080 patients total. Hazard ratios with 95% confidence intervals calculated for each outcome.","limitations":"Meta-analysis pools trials with different GLP-1 drugs, durations, and populations. Benefits were not significantly different between patients with and without existing heart disease, but heterogeneity analysis may be underpowered. Kidney benefit was driven by albumin changes, not hard renal endpoints like dialysis."},{"rthcId":"RPEP-05409","title":"The Role of Galcanezumab in Migraine Prevention: Existing Data and Future Directions.","authors":"Gklinos, Panagiotis; Mitsikostas, Dimos D","year":2021,"journal":"Pharmaceuticals (Basel, Switzerland), 14(3)","doi":"10.3390/ph14030245","pmid":"33803190","tags":["neuropeptides","pain","clinical-trials"],"studyType":"Review","evidenceStrength":"Moderate","keyFinding":"Four phase-3 RCTs demonstrated galcanezumab is superior to placebo in reducing migraine headache frequency, improving migraine-specific quality of life, and reducing headache-related disability.","whyItMatters":"Galcanezumab is one of four anti-CGRP antibodies that represent the first migraine-specific preventive treatments. Unlike older preventives borrowed from other conditions, these drugs target the actual biology of migraine.","specificNumbers":"4 phase-3 RCTs; also studied in cluster headache; most AEs mild to moderate","methodology":"Narrative review of pharmacological properties, clinical trial data from four phase-3 randomized placebo-controlled trials, and safety/tolerability profiles of galcanezumab.","limitations":"Review article with no original data. Long-term cardiovascular safety remains unclear. Limited data in treatment-resistant migraine. Cluster headache data needs more trials to confirm."},{"rthcId":"RPEP-05410","title":"Semax, synthetic ACTH(4-10) analogue, attenuates behavioural and neurochemical alterations following early-life fluvoxamine exposure in white rats.","authors":"Glazova, Nataliya Yu; Manchenko, Daria M; Volodina, Maria A; Merchieva, Svetlana A; Andreeva, Ludmila A; Kudrin, Vladimir S; Myasoedov, Nikolai F; Levitskaya, Natalia G","year":2021,"journal":"Neuropeptides, 86, 102114","doi":"10.1016/j.npep.2020.102114","pmid":"33418449","tags":["semax","neuroprotection","anxiety-mood"],"studyType":"Preclinical Animal Study","evidenceStrength":"Preliminary","keyFinding":"Neonatal fluvoxamine (postnatal days 1-14) caused long-term anxiety, impaired learning, and altered brain monoamines. Subsequent Semax treatment (postnatal days 15-28) reduced anxiety, improved learning, and normalized brain biogenic amine levels.","whyItMatters":"Millions of pregnant women take SSRIs, and concerns about effects on fetal brain development persist. If Semax can reverse SSRI-induced developmental changes, it could protect exposed infants — though much more research is needed before any human application.","specificNumbers":"Postnatal days 1-14 fluvoxamine; days 15-28 Semax; anxiety reduced; learning improved; monoamines normalized at 1-2 months","methodology":"Animal study. Rat pups received fluvoxamine or vehicle (postnatal days 1-14, equivalent to human 27-40 weeks gestation). Then Semax or vehicle (postnatal days 15-28). Behavioral testing at 1-2 months: anxiety, food-motivated maze learning. Brain monoamine levels measured.","limitations":"Rat model with neonatal (not prenatal) drug exposure. Human fetal brain development differs from rodent. Semax is not approved in most countries. Long-term effects of Semax itself on developing brains not fully characterized. Small animal study."},{"rthcId":"RPEP-05411","title":"Hydrogen Bonding Stiffens Peptide Amphiphile Supramolecular Filaments by Aza-Glycine Residues.","authors":"Godbe, Jacqueline M; Freeman, Ronit; Lewis, Jacob A; Sasselli, Ivan R; Sangji, M Hussain; Stupp, Samuel I","year":2021,"journal":"Acta biomaterialia, 135, 87-99","doi":"10.1016/j.actbio.2021.08.044","pmid":"34481055","tags":["peptide-design","peptide-delivery","neuroprotection"],"studyType":"In Vitro Study","evidenceStrength":"Preliminary","keyFinding":"5 mol% azaG substitution increased nanofiber persistence length 5-fold. Scaffold bioactivity toward iPSC-derived dopaminergic neurons was enhanced by persistence length independently of bulk storage modulus, improving neuron survival and tyrosine hydroxylase expression.","whyItMatters":"Parkinson's disease destroys dopaminergic neurons. Growing replacement neurons on optimized peptide scaffolds could advance cell therapy approaches. The finding that cells sense nanoscale rather than bulk stiffness changes how we design biomaterials for neural regeneration.","specificNumbers":"5 mol% azaG = 5x persistence length; 10 mol% optimal for bulk G'; improved TH expression in iPSC-derived neurons","methodology":"In vitro study. Peptide amphiphiles with aza-glycine substitutions self-assembled into nanofibers. Persistence length measured by microscopy, diffusion by FRAP, bulk modulus by rheology. Bioactivity tested with iPSC-derived dopaminergic neurons in 3D hydrogel culture.","limitations":"In vitro iPSC-derived neuron culture only. No in vivo testing for Parkinson's application. Long-term neuron functionality and scaffold degradation not assessed. Manufacturing azaG-containing peptides may be more complex."},{"rthcId":"RPEP-05412","title":"Discovery of thymosin β4 as a human exerkine and growth factor.","authors":"Gonzalez-Franquesa, Alba; Stocks, Ben; Borg, Melissa L; Kuefner, Michael; Dalbram, Emilie; Nielsen, Thomas S; Agrawal, Ankita; Pankratova, Stanislava; Chibalin, Alexander V; Karlsson, Håkan K R; Gheibi, Sevda; Björnholm, Marie; Jørgensen, Niklas Rye; Clemmensen, Christoffer; Hostrup, Morten; Treebak, Jonas T; Krook, Anna; Zierath, Juleen R; Deshmukh, Atul S","year":2021,"journal":"American journal of physiology. Cell physiology, 321(5), C770-C778","doi":"10.1152/ajpcell.00263.2021","pmid":"34495765","tags":["thymosin-beta-4","bone-joint","neuroprotection","muscle-recovery","hormone-optimization"],"studyType":"Mixed Methods (Proteomics, Human Observational, Animal, In Vitro)","evidenceStrength":"Moderate","keyFinding":"TMSB4X was the most upregulated secreted protein from contracting C2C12 myotubes by MS-based proteomics, and was acutely increased in plasma of exercising humans irrespective of insulin resistance status.","whyItMatters":"Identifying thymosin beta-4 as a major exerkine could explain how exercise promotes tissue repair, cardiovascular health, and brain protection. It opens the possibility of using TMSB4X therapeutically as an \"exercise mimetic\" for people who cannot exercise.","specificNumbers":"Most upregulated secreted protein; acutely elevated in human plasma; increased osteoblast proliferation; promoted neurite outgrowth; no metabolic benefit in obese mice","methodology":"Proteomics study. MS-based secretome analysis of contracting C2C12 myotubes in vitro. Human plasma TMSB4X levels measured during exercise in subjects with and without insulin resistance.","limitations":"Initial discovery from in vitro muscle cell model. Human plasma measurements were acute (exercise session), not chronic. Functional significance of exercise-induced TMSB4X increase needs further investigation. Dose-response and tissue-specific effects unknown."},{"rthcId":"RPEP-05413","title":"The impact of CGRPergic monoclonal antibodies on prophylactic antimigraine therapy and potential adverse events.","authors":"González-Hernández, Abimael; Marichal-Cancino, Bruno A; Villalón, Carlos M","year":2021,"journal":"Expert opinion on drug metabolism & toxicology, 17(10), 1223-1235","doi":"10.1080/17425255.2021.1982892","pmid":"34535065","tags":["neuropeptides","pain","peptide-safety","clinical-trials"],"studyType":"Review","evidenceStrength":"Moderate","keyFinding":"Anti-CGRP monoclonal antibodies represent a paradigm shift in migraine prevention as the first treatments designed specifically for migraine. All four (erenumab, fremanezumab, galcanezumab, eptinezumab) have demonstrated efficacy in clinical trials.","whyItMatters":"Understanding how these antibodies compare helps patients and clinicians choose the most appropriate option and understand how they fit alongside existing migraine preventive treatments.","specificNumbers":"4 mAbs; 3 target CGRP; 1 targets CGRP receptor; do not cross BBB; hepato-friendly","methodology":"Narrative review of clinical trial data, prescribing patterns, and safety profiles for anti-CGRP monoclonal antibodies in migraine prevention.","limitations":"Narrative review. Limited head-to-head comparison data between the four antibodies. Long-term safety data still accumulating. Cost and access remain barriers for many patients."},{"rthcId":"RPEP-05414","title":"Significance of the Overexpression of Substance P and Its Receptor NK-1R in Head and Neck Carcinogenesis: A Systematic Review and Meta-Analysis.","authors":"González-Moles, Miguel Ángel; Ramos-García, Pablo; Esteban, Francisco","year":2021,"journal":"Cancers, 13(6)","doi":"10.3390/cancers13061349","pmid":"33802704","tags":["neuropeptides","cancer"],"studyType":"Systematic Review & Meta-Analysis","evidenceStrength":"Moderate","keyFinding":"SP/NK-1R overexpression was significantly higher in malignant vs benign head and neck lesions (P=0.02), with NK-1R showing greater overexpression than SP (P=0.02).","whyItMatters":"If substance P and NK-1R drive early cancer development in the head and neck, NK-1R antagonists (drugs that already exist for other uses like nausea) could potentially be repurposed for cancer prevention or treatment.","specificNumbers":"16 studies; 1,308 cases; P=0.02 malignant vs benign; P=0.02 NK-1R > SP; salivary gland cancers also positive","methodology":"Systematic review and meta-analysis following PRISMA guidelines. Searched PubMed, Embase, Web of Science, and Scopus for studies published before May 2020. Quality assessed with QUIPS tool. Heterogeneity, sensitivity, small-study effects, and subgroup analyses performed. 16 studies with 1,308 cases met inclusion criteria.","limitations":"Study quality varied, with the greatest risk of bias in confounding and prognostic factors. Heterogeneous study designs and methods. Cannot prove that SP/NK-1R overexpression causes cancer rather than being a consequence of it. Limited to head and neck cancers."},{"rthcId":"RPEP-05415","title":"The RaPID Platform for the Discovery of Pseudo-Natural Macrocyclic Peptides.","authors":"Goto, Yuki; Suga, Hiroaki","year":2021,"journal":"Accounts of chemical research, 54(18), 3604-3617","doi":"10.1021/acs.accounts.1c00391","pmid":"34505781","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05416","title":"Snake venom-derived bradykinin-potentiating peptides: A promising therapy for COVID-19?","authors":"Gouda, Ahmed S; Mégarbane, Bruno","year":2021,"journal":"Drug development research, 82(1), 38-48","doi":"10.1002/ddr.21732","pmid":"32761647","tags":["venom-peptides","infection","receptor-signaling"],"studyType":"Review","evidenceStrength":"Low","keyFinding":"BPP-10c acts on both renin-angiotensin and kinin-kallikrein systems: inhibits ACE (reducing angiotensin II), enhances bradykinin B2 receptor effects, and increases nitric oxide — addressing the dual system disruption caused by SARS-CoV-2.","whyItMatters":"COVID-19 treatments targeting only one disrupted system may be insufficient. A peptide that corrects both the angiotensin II excess and bradykinin imbalance could provide more comprehensive treatment.","specificNumbers":"BPP-10c inhibits ACE; boosts bradykinin B2 effects; increases nitric oxide; dual RAS/KKS action","methodology":"Narrative review of SARS-CoV-2 effects on renin-angiotensin and kinin-kallikrein systems, with theoretical analysis of BPP-10c as a therapeutic candidate.","limitations":"Entirely theoretical — BPP-10c has not been tested in COVID-19 patients or animal models. The dual system hypothesis, while logical, requires experimental validation. BPP-10c delivery, stability, and safety in acute illness are unknown."},{"rthcId":"RPEP-05417","title":"Calcitonin Gene-Related Peptide Monoclonal Antibody Use for the Preventive Treatment of Refractory Headache Disorders in Adolescents.","authors":"Greene, Kaitlin A; Gentile, Carlyn P; Szperka, Christina L; Yonker, Marcy; Gelfand, Amy A; Grimes, Barbara; Irwin, Samantha L","year":2021,"journal":"Pediatric neurology, 114, 62-67","doi":"10.1016/j.pediatrneurol.2020.09.014","pmid":"33232919","tags":["neuropeptides","pain","clinical-trials","side-effects"],"studyType":"Retrospective Cohort","evidenceStrength":"Moderate","keyFinding":"In 112 adolescents, CGRP mAbs reduced headache frequency by 2.0 days/month (95% CI -0.8 to -3.2). 29.5% perceived significant benefit. 31% reported functional improvement. Side effects were mild and similar to adults. 4.5% discontinued for side effects.","whyItMatters":"Adolescents with chronic migraine have very limited treatment options and often miss significant school time. This first evidence of CGRP antibody safety and efficacy in teens could expand treatment access for a vulnerable population.","specificNumbers":"112 adolescents; mean age 15.9; 26.9 headache days/month baseline; -2.0 days reduction; 29.5% significant benefit; 17% injection site reactions; 4.5% discontinuation","methodology":"Retrospective multisite cohort study. 112 patients <18 years receiving CGRP mAbs for headache prevention. Demographics, headache characteristics, efficacy, and side effects collected. Mean age 15.9 years. 83.9% chronic migraine.","limitations":"Retrospective study without a control group. Modest average response (2 fewer days/month from a baseline of 27). Only 30% perceived significant benefit. Short follow-up. Self-selected population with highly refractory headache."},{"rthcId":"RPEP-05418","title":"UVR-B-induced NKR-1 Expression in Ocular Tissues is blocked by Substance P Receptor Antagonist Fosaprepitant in the Exposed as well as Unexposed Partner Eye.","authors":"Gross, Janine; Wegener, Alfred R; Kronschläger, Martin; Schönfeld, Carl-Ludwig; Holz, Frank G; Meyer, Linda M","year":2021,"journal":"Ocular immunology and inflammation, 29(5), 963-975","doi":"10.1080/09273948.2019.1708414","pmid":"32058829","tags":["neuropeptides","eye-health","inflammation"],"studyType":"Preclinical Animal Study","evidenceStrength":"Preliminary","keyFinding":"Fosaprepitant (NK-1R antagonist) blocked UVR-B-induced NKR-1 expression and pro-inflammatory cytokine/chemokine production in both exposed and unexposed partner eyes in a mouse cataract model.","whyItMatters":"UV-related eye damage is a global health concern. Discovering that substance P mediates bilateral eye inflammation from unilateral UV exposure — and that it can be blocked — opens new prevention strategies using existing drugs.","specificNumbers":"NK-1R reduced in exposed tissues; NK-1R reduced in unexposed lens epithelium; no cytokine changes; days 3 and 7 endpoints","methodology":"Animal study. UVR-B-induced cataract mouse model. Unilateral UV exposure. Fosaprepitant treatment. NK-1R expression and pro-inflammatory cytokine/chemokine levels measured in both exposed and unexposed eyes.","limitations":"Mouse model only. Fosaprepitant was given systemically, so off-target effects possible. Long-term cataract prevention not assessed. Bilateral mechanism not fully explained."},{"rthcId":"RPEP-05419","title":"Diverse Mechanisms of Antimicrobial Activities of Lactoferrins, Lactoferricins, and Other Lactoferrin-Derived Peptides.","authors":"Gruden, Špela; Poklar Ulrih, Nataša","year":2021,"journal":"International journal of molecular sciences, 22(20)","doi":"10.3390/ijms222011264","pmid":"34681923","tags":["antimicrobial-peptides","infection","bioactive-food-peptides"],"studyType":"Review","evidenceStrength":"Low","keyFinding":"Lactoferrins and lactoferricins employ diverse antimicrobial mechanisms including iron sequestration, membrane disruption, biofilm inhibition, immunomodulation, anti-inflammatory, and antioxidant activities across bacteria, viruses, fungi, and parasites.","whyItMatters":"Antibiotic resistance is a growing crisis. Lactoferrin and lactoferricins attack pathogens through so many different mechanisms that resistance development is much harder — making them promising candidates for next-generation anti-infective therapies.","specificNumbers":"Lactoferricin discovered 30 years ago; higher activity than native lactoferrin; active against bacteria, viruses, fungi, parasites","methodology":"Narrative review of published literature on lactoferrin and lactoferrin-derived peptide antimicrobial mechanisms.","limitations":"Narrative review. Most evidence is from in vitro and animal studies. Clinical trials of lactoferrin as an antimicrobial agent are limited. Optimal dosing and delivery for clinical use remain unclear."},{"rthcId":"RPEP-05420","title":"Herpes Simplex Virus-1 infection in human primary corneal epithelial cells is blocked by a stapled peptide that targets processive DNA synthesis.","authors":"Guan, Hancheng; Nuth, Manunya; Lee, Vivian; Lin, Chenyan; Mitchell, Claire H; Lu, Wennan; Scott, Richard W; Parker, Michael H; Kulp, John L; Reitz, Allen B; Ricciardi, Robert P","year":2021,"journal":"The ocular surface, 19, 313-321","doi":"10.1016/j.jtos.2020.11.001","pmid":"33161128","tags":["cyclic-peptides","infection","eye-health","peptide-design"],"studyType":"In Vitro Study","evidenceStrength":"Preliminary","keyFinding":"Optimized di-valine stapled peptide blocked HSV-1 DNA synthesis and infection in human primary corneal epithelial cells with selectivity index of 11.6. Unstapled control peptide had no effect. Peptide did not block unrelated virus infection (specificity confirmed).","whyItMatters":"Acyclovir-resistant herpes is a growing clinical problem, especially for eye infections that can cause blindness. A peptide targeting a completely different viral protein provides a fallback treatment option.","specificNumbers":"Selectivity index 11.6; di-valine optimization; specific to HSV-1; unstapled control had no effect","methodology":"Structure-based peptide design from HSV-1 polymerase C-terminus crystal structure. Hydrocarbon stapling to maintain α-helical conformation. Testing of DNA synthesis inhibition, HSV-1 infection blocking, and specificity in human primary corneal epithelial cells.","limitations":"In vitro study in human corneal cells only. Selectivity index of 11.6 is modest for drug development. Topical eye formulation, stability, and penetration not tested. In vivo efficacy in animal models of herpes keratitis not assessed."},{"rthcId":"RPEP-05421","title":"Increased expression of transient receptor potential channels and neurogenic factors associates with cough severity in a guinea pig model.","authors":"Guan, Mengyue; Ying, Sun; Wang, Yuguang","year":2021,"journal":"BMC pulmonary medicine, 21(1), 187","doi":"10.1186/s12890-021-01556-w","pmid":"34078339","tags":["neuropeptides","respiratory","inflammation"],"studyType":"Preclinical Animal Study","evidenceStrength":"Preliminary","keyFinding":"Bleomycin-induced pulmonary fibrosis in guinea pigs caused significantly increased expression of substance P, NK1R, CGRP, TRPA1, and TRPV1 in cough reflex pathways, all positively correlated with enhanced cough sensitivity to capsaicin challenge.","whyItMatters":"Cough in IPF has no effective treatment. Identifying substance P, CGRP, and TRP channels as drivers opens the door to targeting these neuropeptides — potentially using existing drugs like NK1R antagonists or anti-CGRP antibodies — for a currently untreatable symptom.","specificNumbers":"TRPA1/TRPV1 upregulated in ganglia; SP/NK1R/CGRP upregulated in lung; positive correlation with cough sensitivity; NGF/NKA/NKB/BDNF also measured","methodology":"Animal study. Bleomycin-induced pulmonary fibrosis guinea pig model. Cough sensitivity to capsaicin measured. Neuropeptide expression (SP, NK1R, CGRP) by immunohistochemistry and RT-qPCR. TRP channel expression by Western blot and RT-qPCR. Neurogenic factor concentrations by ELISA.","limitations":"Guinea pig model — may not fully replicate human IPF cough. Bleomycin-induced fibrosis differs from naturally occurring IPF. Correlation between neuropeptides and cough doesn't prove causation. Small animal numbers likely."},{"rthcId":"RPEP-05422","title":"Target-templated de novo design of macrocyclic d-/l-peptides: discovery of drug-like inhibitors of PD-1.","authors":"Guardiola, Salvador; Varese, Monica; Roig, Xavier; Sánchez-Navarro, Macarena; García, Jesús; Giralt, Ernest","year":2021,"journal":"Chemical science, 12(14), 5164-5170","doi":"10.1039/d1sc01031j","pmid":"34163753","tags":["cyclic-peptides","cancer","peptide-design"],"studyType":"Computational & Biophysical Study","evidenceStrength":"Preliminary","keyFinding":"Two de novo designed heterochiral macrocyclic peptides (PD-i3, PD-i6) bind PD-1 and block the PD-1/PD-L1 interaction. NMR elucidation confirmed computational structure predictions. The Rosetta framework enables generalizable design of target-specific cyclic peptides.","whyItMatters":"Current PD-1 checkpoint inhibitors are expensive antibodies requiring IV infusion. Small cyclic peptides could potentially be cheaper, more stable, and potentially orally available — democratizing access to cancer immunotherapy.","specificNumbers":"2 lead peptides (PD-i3, PD-i6); heterochiral D/L design; Rosetta framework; NMR-confirmed structures; block PD-1/PD-L1","methodology":"Computational de novo design using Rosetta with large-scale backbone sampling, side-chain composition, and energy scoring. Heterochiral (D/L) cyclic peptide synthesis. Biophysical evaluation of PD-1 binding and PD-L1 blocking. NMR structure confirmation.","limitations":"Biophysical binding data only — no cell-based or in vivo anti-tumor efficacy testing. Binding affinity compared to antibody checkpoint inhibitors not reported. Oral bioavailability and stability in biological fluids not assessed."},{"rthcId":"RPEP-05423","title":"Discovery of KV 1.3 ion channel inhibitors: Medicinal chemistry approaches and challenges.","authors":"Gubič, Špela; Hendrickx, Louise A; Toplak, Žan; Sterle, Maša; Peigneur, Steve; Tomašič, Tihomir; Pardo, Luis A; Tytgat, Jan; Zega, Anamarija; Mašič, Lucija P","year":2021,"journal":"Medicinal research reviews, 41(4), 2423-2473","doi":"10.1002/med.21800","pmid":"33932253","tags":["venom-peptides","immune-function","inflammation","cancer","peptide-design","clinical-trials"],"studyType":"Review","evidenceStrength":"Moderate","keyFinding":"KV1.3 ion channel inhibitors derived from venom peptides selectively suppress effector memory T cells involved in autoimmune diseases, with multiple medicinal chemistry approaches being pursued to optimize them as therapeutics.","whyItMatters":"Current immunosuppressants have broad side effects. KV1.3-selective peptides could suppress autoimmune T cells specifically without the wide immunosuppression of current drugs like cyclosporine or methotrexate.","specificNumbers":"ShK-186 (dalatazide) in clinical trials; targets KV1.3 selectively; derived from sea anemone ShK toxin; applications in MS, T1D, psoriasis, RA, cancer","methodology":"Narrative review of KV1.3 biology, venom-derived peptide inhibitors, and medicinal chemistry strategies for drug optimization.","limitations":"Review of mostly preclinical data. No KV1.3 peptide drugs have completed clinical trials for autoimmune diseases. Selectivity between KV1.3 and related channels remains challenging. Peptide delivery and half-life are practical hurdles."},{"rthcId":"RPEP-05424","title":"The therapeutic potential of GLP-1 analogues for stress-related eating and role of GLP-1 in stress, emotion and mood: a review.","authors":"Guerrero-Hreins, Eva; Goldstone, Anthony P; Brown, Robyn M; Sumithran, Priya","year":2021,"journal":"Progress in neuro-psychopharmacology & biological psychiatry, 110, 110303","doi":"10.1016/j.pnpbp.2021.110303","pmid":"33741445","tags":["glp-1","anxiety-mood","weight-loss","addiction"],"studyType":"Review","evidenceStrength":"Low","keyFinding":"Acute GLP-1 injection consistently stimulates the physiological stress response in rodents (increased stress hormones). Long-term GLP-1 exposure shows anxiolytic and antidepressant-like effects in animal models. In clinical studies, prolonged GLP-1 analogue treatment in type 2 diabetes patients improved mood and general psychological wellbeing. However, these clinical benefits may be confounded by associated weight loss and improved glycemic control. GLP-1 acts on brain areas involved in stress response and emotion regulation, supporting a potential direct role beyond appetite suppression.","whyItMatters":"Stress eating is one of the biggest barriers to sustainable weight management, and current obesity treatments don't directly address it. If GLP-1 drugs work partly by modifying the brain's stress and emotion circuits — not just suppressing appetite — they could be uniquely effective for the millions of people whose weight gain is driven by emotional eating. Understanding this mechanism could also help identify which patients will benefit most.","specificNumbers":"Acute GLP-1 increases stress hormones; chronic GLP-1 reduces anxiety/depression in animals; clinical mood benefits confounded by weight loss","methodology":"Narrative review of preclinical and clinical literature examining GLP-1's role in stress response, emotion regulation, mood, and stress-related eating behavior. Searched for studies measuring markers of stress, anxiety, and mood after GLP-1 exposure in both animal models and human subjects.","limitations":"Narrative review without systematic methodology. Animal findings (acute stress activation, chronic anxiolysis) may not directly translate to humans. Clinical mood improvements in diabetes patients are confounded by weight loss, better blood sugar, and improved self-image — making it impossible to isolate GLP-1's direct brain effects. Very limited longitudinal clinical data on the specific pathways by which GLP-1 modifies stress-related eating. Published in 2021, before the explosion of interest in GLP-1 neuropsychiatric effects."},{"rthcId":"RPEP-05425","title":"Timeline of Changes in Biomarkers Associated with Spinal Cord Injury-Induced Polyuria.","authors":"Gumbel, Jason H; Yang, Cui Bo; Hubscher, Charles H","year":2021,"journal":"Neurotrauma reports, 2(1), 462-475","doi":"10.1089/neur.2021.0046","pmid":"34901942","tags":["natriuretic-peptides","neuropeptides"],"studyType":"Preclinical Animal Study","evidenceStrength":"Preliminary","keyFinding":"Spinal cord injury caused significant fluctuations in atrial natriuretic peptide, vasopressin, kidney water channels (aquaporin-2), and sodium channels beginning 7 days post-injury.","whyItMatters":"Excessive urination after spinal cord injury reduces quality of life but is poorly understood. This study maps the timeline of hormonal changes, showing the problem starts early and suggesting treatment should too.","specificNumbers":"Changes from day 7; ANP, AVP, NPR-A, V2R, AQP-2, ENaC subunits all altered; hypothalamic AVP neurons changed","methodology":"Animal study in adult male Wistar rats with contusion spinal cord injury. Time-course measurement of urinary ANP, serum AVP, kidney receptor/channel expression, and hypothalamic AVP neuron counts at multiple post-injury time points.","limitations":"Animal study in rats. Contusion model may not perfectly represent human SCI. Only male rats studied. Functional urinary outcomes (volume, concentration) not detailed in abstract. Desmopressin treatment was suggested but not tested."},{"rthcId":"RPEP-05426","title":"A novel peptide identified from skin secretions of Bombina maxima possesses LPS-neutralizing activity.","authors":"Guo, Caifen; Li, Jian; Lee, WenHui; Li, Hao; Shen, Jihong; Zhang, Baiyu","year":2021,"journal":"Biochemical and biophysical research communications, 550, 107-112","doi":"10.1016/j.bbrc.2021.02.131","pmid":"33689880","tags":["antimicrobial-peptides","infection","inflammation"],"studyType":"Preclinical (In Vitro + Animal)","evidenceStrength":"Preliminary","keyFinding":"Peptide 2 (LVGKLLKGAVGDVCGLLPIC) binds LPS with KD of 1.05 × 10⁻⁹ M, inhibits TNF-α and IL-6, has low hemolytic activity and cytotoxicity, and protected mice from LPS-induced death.","whyItMatters":"Sepsis kills more than 11 million people annually worldwide. A peptide that directly neutralizes the bacterial toxin driving sepsis could save lives where antibiotics alone fail — addressing a critical unmet medical need.","specificNumbers":"KD 1.05 x 10^-9 M; 20 amino acids; reduced TNF-alpha and IL-6; protected mice from LPS death; low hemolysis","methodology":"Peptide identified from B. maxima skin secretions after LPS challenge. Characterized for hemolytic activity, cytotoxicity (RAW 264.7 cells), anti-inflammatory activity (TNF-α, IL-6 inhibition), LPS binding (biolayer interferometry), and in vivo survival study in LPS-challenged mice.","limitations":"Single peptide tested. Mouse LPS challenge model may differ from human sepsis. Peptide stability, pharmacokinetics, and manufacturing scalability not assessed. In vivo anti-sepsis efficacy in infection models (not just LPS challenge) not tested."},{"rthcId":"RPEP-05427","title":"Impact of dietary intake of resistant starch on obesity and associated metabolic profiles in human: a systematic review of the literature.","authors":"Guo, Jiayue; Tan, Libo; Kong, Lingyan","year":2021,"journal":"Critical reviews in food science and nutrition, 61(6), 889-905","doi":"10.1080/10408398.2020.1747391","pmid":"32321291","tags":["glp-1","bioactive-food-peptides","diabetes","weight-loss"],"studyType":"Systematic Review","evidenceStrength":"Moderate","keyFinding":"RS intake significantly improved GLP-1 and PYY gut hormone levels, improved blood glucose (5/8 studies) and insulin sensitivity (2/3 studies). No consistent effect on body weight, body composition, energy intake, or lipid profiles.","whyItMatters":"Understanding that resistant starch boosts appetite hormones without reliably reducing weight helps set realistic expectations. The metabolic benefits (glucose, insulin) may justify RS intake even without weight loss.","specificNumbers":"11 studies; no weight effect; 5/8 lower glucose; 2/3 better insulin sensitivity; GLP-1 and PYY increased","methodology":"Systematic review. 11 peer-reviewed articles (2000-2019) from CENTRAL, MEDLINE, CINAHL Plus. Outcomes: body weight/composition, energy intake, satiety, lipid profiles, blood glucose/insulin, gut hormones.","limitations":"Only 11 studies met criteria — limited evidence base. Studies varied in RS type, dose, duration, and population. Most studies were small and short-term. Publication bias possible."},{"rthcId":"RPEP-05428","title":"In silico identification and experimental validation of cellular uptake and intracellular labeling by a new cell penetrating peptide derived from CDN1.","authors":"Guo, Xiangli; Chen, Linlin; Wang, Lidan; Geng, Jingping; Wang, Tao; Hu, Jixiong; Li, Jason; Liu, Changbai; Wang, Hu","year":2021,"journal":"Drug delivery, 28(1), 1722-1736","doi":"10.1080/10717544.2021.1963352","pmid":"34463179","tags":["cell-penetrating","peptide-delivery","peptide-design"],"studyType":"In Vitro Study","evidenceStrength":"Preliminary","keyFinding":"A novel CPP derived from CDN1 was identified through in silico screening and experimentally validated for cellular uptake and intracellular labeling in living cells.","whyItMatters":"Many promising drugs can't get inside cells. Each new CPP discovered adds to the toolkit for intracellular drug delivery, and computational identification accelerates discovery compared to trial-and-error approaches.","specificNumbers":"CDN1-derived; concentration-dependent; receptor-mediated endocytosis; no hemolysis; HaloTag delivery confirmed","methodology":"Computational (in silico) screening for CPP sequences in CDN1 protein. Peptide synthesis. Experimental validation of cellular uptake and intracellular labeling by fluorescence microscopy.","limitations":"Basic cellular uptake validation only. Cargo delivery capacity not tested. Cell type specificity not characterized. In vivo behavior unknown."},{"rthcId":"RPEP-05429","title":"Regulation of Opioid Receptors by Their Endogenous Opioid Peptides.","authors":"Gupta, Achla; Gullapalli, Srinivas; Pan, Hui; Ramos-Ortolaza, Dinah L; Hayward, Michael D; Low, Malcom J; Pintar, John E; Devi, Lakshmi A; Gomes, Ivone","year":2021,"journal":"Cellular and molecular neurobiology, 41(5), 1103-1118","doi":"10.1007/s10571-020-01015-w","pmid":"33389463","tags":["opioid-peptides","pain","receptor-signaling"],"studyType":"Preclinical Animal Study","evidenceStrength":"Moderate","keyFinding":"Loss of beta-endorphin and/or proenkephalin caused differential, region-specific, and sex-specific modulation of mu, delta, and kappa opioid receptor expression and activity, with no compensatory increase in dynorphin-derived peptides.","whyItMatters":"Opioid receptors are major drug targets for pain, addiction, and mood. Knowing that the body's own opioid peptides regulate these receptors helps explain individual differences in pain sensitivity and addiction vulnerability.","specificNumbers":"3 knockout types; mu/delta/kappa all affected; region-specific; sex-specific; Leu-enkephalin mainly from proenkephalin; no dynorphin compensation","methodology":"Knockout mouse study. Mice lacking proenkephalin, beta-endorphin, or both were compared to wild-type. Leu-enkephalin and dynorphin levels measured by mass spectrometry. Opioid receptor levels and G-protein activity measured in specific brain regions. Males and females compared.","limitations":"Mouse knockout study. Complete absence of a peptide from birth does not mimic natural human variation. Compensatory developmental changes may mask acute effects. Cannot directly extrapolate sex differences to humans."},{"rthcId":"RPEP-05430","title":"High Coexpression of the Ghrelin and LEAP2 Receptor GHSR With Pancreatic Polypeptide in Mouse and Human Islets.","authors":"Gupta, Deepali; Dowsett, Georgina K C; Mani, Bharath K; Shankar, Kripa; Osborne-Lawrence, Sherri; Metzger, Nathan P; Lam, Brian Y H; Yeo, Giles S H; Zigman, Jeffrey M","year":2021,"journal":"Endocrinology, 162(10)","doi":"10.1210/endocr/bqab148","pmid":"34289060","tags":["ghrp","receptor-signaling","diabetes","hormone-optimization"],"studyType":"Mixed Methods (Reporter Mouse, Transcriptomics, In Vivo)","evidenceStrength":"Moderate","keyFinding":"In mice, 85% of GHSR-expressing islet cells coexpress PP and 50% coexpress SST. In humans, 59% coexpress PPY and 95% coexpress SST. GHSR expression is upregulated in beta cells by T2DM. LEAP2 and GHSR antagonists elevated plasma PP.","whyItMatters":"Understanding where ghrelin acts in the pancreas is critical for developing ghrelin-based diabetes therapies. Finding PP cells as primary targets redefines how ghrelin and LEAP2 regulate pancreatic function.","specificNumbers":"85% GHSR cells coexpress PP (mouse); 59% in human; 95% coexpress SST (mouse); GHSR upregulated in T2D beta cells; LEAP2 elevates plasma PP","methodology":"Histochemical analysis using Ghsr-IRES-Cre reporter mice. Single-cell transcriptomics of mouse and human pancreas. Plasma PP correlations with fat mass and LEAP2. PP response to GHSR antagonist and LEAP2 administration.","limitations":"Reporter mouse approach may not capture all GHSR-expressing cells. Single-cell transcriptomics detects mRNA, which may not perfectly reflect protein expression. Human data from multiple datasets with variable methodology. Functional significance of GHSR on PP cells needs testing."},{"rthcId":"RPEP-05431","title":"In Vitro-Evolved Peptides Bind Monomeric Actin and Mimic Actin-Binding Protein Thymosin-β4.","authors":"Gübeli, Raphael J; Bertoldo, Davide; Shimada, Kenji; Gerhold, Christian B; Hurst, Verena; Takahashi, Yuichiro; Harada, Kai; Mothukuri, Ganesh K; Wilbs, Jonas; Harata, Masahiko; Gasser, Susan M; Heinis, Christian","year":2021,"journal":"ACS chemical biology, 16(5), 820-828","doi":"10.1021/acschembio.0c00825","pmid":"33843189","tags":["thymosin-beta-4","cyclic-peptides","peptide-design"],"studyType":"In Vitro Study","evidenceStrength":"Preliminary","keyFinding":"In vitro-evolved peptides bind monomeric actin and functionally mimic thymosin beta-4, the natural actin-sequestering protein. These represent the first synthetic probes for monomeric actin.","whyItMatters":"Thymosin beta-4 is being studied for wound healing, cardiac repair, and neuroprotection. Synthetic peptides that mimic its actin-binding function could lead to more drugable versions with improved stability and specificity.","specificNumbers":">10 billion peptides screened; low nM affinity; >1,000-fold G/F-actin selectivity; thymosin beta-4 binding site; failed in intact cells","methodology":"In vitro evolution/selection of peptide libraries. Binding to monomeric actin characterized. Structural comparison to thymosin beta-4 actin-binding mechanism. First synthetic monomeric actin-binding probes developed.","limitations":"In vitro binding study only. Functional mimicry of TB4's therapeutic effects (wound healing, tissue repair) not tested. Peptide stability, bioavailability, and in vivo activity not assessed."},{"rthcId":"RPEP-05432","title":"Effect of combined therapy of mesenchymal stem cells with GLP-1 receptor agonist, exenatide, on early-onset nephropathy induced in diabetic rats.","authors":"Habib, Heba A; Heeba, Gehan H; Khalifa, Mohamed M A","year":2021,"journal":"European journal of pharmacology, 892, 173721","doi":"10.1016/j.ejphar.2020.173721","pmid":"33159934","tags":["exenatide","glp-1","kidney","diabetes"],"studyType":"Preclinical Animal Study","evidenceStrength":"Preliminary","keyFinding":"Combined ADMSC + exenatide therapy showed superior renoprotective effects versus ADMSCs alone in diabetic rats, with significant improvement in kidney function and reduced inflammatory, fibrotic, and apoptotic markers.","whyItMatters":"Diabetic kidney disease affects hundreds of millions. If GLP-1 drugs can enhance stem cell therapy, it could create a more effective regenerative treatment for a condition that currently progresses to dialysis in many patients.","specificNumbers":"Combination > ADMSC alone > exenatide alone; reduced TNF-alpha, TGF-beta1, caspase-3; improved kidney function and architecture; 4-week treatment","methodology":"Animal study. Type 2 diabetic rats treated with adipose-derived MSCs, exenatide, or combination 4 weeks post-induction. Kidney function, histology, oxidative stress, TNF-α, TGF-β1, and cleaved caspase-3 assessed 4 weeks after treatment.","limitations":"Rat model of type 2 diabetes — may not fully replicate human diabetic nephropathy. Short treatment period (4 weeks). Specific mechanisms of synergy between exenatide and stem cells not fully elucidated. No long-term follow-up."},{"rthcId":"RPEP-05433","title":"Identification and Metabolic Profiling of a Novel Human Gut-derived LEAP2 Fragment.","authors":"Hagemann, Christoffer A; Zhang, Chen; Hansen, Henrik H; Jorsal, Tina; Rigbolt, Kristoffer T G; Madsen, Martin R; Bergmann, Natasha C; Heimbürger, Sebastian M N; Falkenhahn, Mechthilde; Theis, Stefan; Breitschopf, Kristin; Holm, Stephanie; Hedegaard, Morten A; Christensen, Mikkel B; Vilsbøll, Tina; Holst, Birgitte; Vrang, Niels; Jelsing, Jacob; Knop, Filip K","year":2021,"journal":"The Journal of clinical endocrinology and metabolism, 106(2), e966-e981","doi":"10.1210/clinem/dgaa803","pmid":"33135737","tags":["glp-1","diabetes","receptor-signaling","hormone-optimization"],"studyType":"Translational (Gene Expression + In Vitro + Human Infusion)","evidenceStrength":"Moderate","keyFinding":"RYGB upregulated LEAP2 expression. LEAP2₃₈₋₄₇ demonstrated robust insulinotropic activity comparable to GLP-1 in human islets, likely via GHSR attenuation. But IV infusion in 10 healthy humans at the chosen dose showed no glucoregulatory effect.","whyItMatters":"Understanding how RYGB improves diabetes could lead to non-surgical treatments. LEAP2 is a novel metabolic peptide that could be developed as a new diabetes drug, though the dose and patient population need optimization.","specificNumbers":"LEAP2 upregulated post-RYGB; LEAP238-47 insulinotropic comparable to GLP-1; 10 subjects infused; no glucoregulatory effect at chosen dose","methodology":"Genome-wide expression in isolated human intestinal enteroendocrine cells from 20 obese subjects pre/post-RYGB. LEAP2₃₈₋₄₇ tested for insulin secretion in human islets and GHSR activity. Phase 1 infusion study in 10 healthy volunteers.","limitations":"Healthy volunteer infusion study — diabetic patients might respond differently. Dose may have been too low. In vitro insulinotropic activity didn't translate in vivo at the tested dose. Small clinical sample (n=10)."},{"rthcId":"RPEP-05434","title":"Appetite and Energy Intake Regulation in Response to Acute Exercise.","authors":"Halliday, Tanya M; White, Mollie H; Hild, Allison K; Conroy, Molly B; Melanson, Edward L; Cornier, Marc-Andre","year":2021,"journal":"Medicine and science in sports and exercise, 53(10), 2173-2181","doi":"10.1249/MSS.0000000000002678","pmid":"33831896","tags":["glp-1","weight-loss","hormone-optimization"],"studyType":"Crossover Trial","evidenceStrength":"Moderate","keyFinding":"Resistance exercise reduced ghrelin (p=0.006), PYY (p=0.001), and GLP-1 (p=0.013) AUC versus aerobic exercise. Neither exercise type increased ad libitum energy intake versus sedentary control (REx 991, AEx 937, SED 944 kcal, p=0.50).","whyItMatters":"Understanding that different exercise types have distinct effects on appetite hormones helps design exercise programs for weight management. The finding that exercise suppresses eating despite lowered satiety hormones suggests non-hormonal appetite control mechanisms.","specificNumbers":"24 adults; ghrelin P=0.006; PYY P=0.001; GLP-1 P=0.013; ~940-991 kcal lunch intake; no condition differences","methodology":"Crossover study. 24 physically inactive adults (35% body fat, 50% female). Three conditions: resistance exercise, aerobic exercise (walking), sedentary control. Appetite hormones (ghrelin, PYY, GLP-1) measured over 180 min. Ad libitum lunch intake assessed.","limitations":"Small study (24 participants). Single exercise bout — chronic effects may differ. Physically inactive population only. Ad libitum meal was laboratory-based. Only measured three appetite hormones."},{"rthcId":"RPEP-05435","title":"Prenatal exposure to valproic acid and treatment with intranasal oxytocin have sex-specific effects on behavior in Long Evans rats.","authors":"Harding, Shannon M; Masters, Ellen C; D'Agata, Christina M; Agudelo Rivera, Aura C; Smith, Emma C","year":2021,"journal":"Behavioural pharmacology, 32(7), 561-570","doi":"10.1097/FBP.0000000000000650","pmid":"34494987","tags":["oxytocin","anxiety-mood","nasal-peptides"],"studyType":"Preclinical Animal Study","evidenceStrength":"Preliminary","keyFinding":"Intranasal oxytocin was anxiolytic for VPA males but anxiogenic for VPA females. In both sexes, oxytocin impaired social interactions in the sociability test and failed to improve sociosexual deficits. Prenatal VPA produced sex-specific behavioral deficits.","whyItMatters":"Oxytocin is being given to autistic children off-label. This study raises important safety concerns: oxytocin may help anxiety but could paradoxically worsen social behavior, and effects differ dramatically between sexes.","specificNumbers":"500 mg/kg VPA GD12; 0.8 IU/kg oxytocin intranasal; anxiolytic in males; anxiogenic in females; impaired sociability both sexes","methodology":"Animal study. Prenatal valproic acid (500 mg/kg, gestational day 12) in Long Evans rats. Intranasal oxytocin (0.8 IU/kg) or saline 30-60 min before testing. Elevated plus maze (anxiety), sociability, partner preference, ultrasonic vocalizations, and scent marking assessed.","limitations":"VPA rat model may not fully replicate human ASD. Single oxytocin dose and timing. Acute administration — chronic effects may differ. Intranasal delivery in rats is imprecise compared to human nasal sprays."},{"rthcId":"RPEP-05436","title":"Tailoring of Peptide Vesicles: A Bottom-Up Chemical Approach.","authors":"Haridas, V","year":2021,"journal":"Accounts of chemical research, 54(8), 1934-1949","doi":"10.1021/acs.accounts.0c00690","pmid":"33823579","tags":["peptide-design","peptide-delivery"],"studyType":"Research Account/Review","evidenceStrength":"Preliminary","keyFinding":"Diverse classes of pseudopeptides (acyclic, cyclic, macrocyclic) can form vesicular assemblies without traditional lipid amphiphile architecture, challenging the long-standing paradigm of vesicle formation.","whyItMatters":"If vesicles can be made from simple peptide building blocks rather than complex lipids, it could simplify drug delivery systems and make them more biocompatible and biodegradable.","specificNumbers":"Multiple pseudopeptide classes; cystine macrocycles for drug encapsulation; polymersomes with novel topology; amino acids: cystine, lysine, leucine, serine","methodology":"Chemical synthesis of diverse pseudopeptide architectures. Self-assembly characterization in aqueous and organic solvents. Drug encapsulation and release studies with cystine-based macrocyclic peptides. Vesiculation mechanism investigation using designer molecules.","limitations":"Review of one lab's work. Most demonstrations are in vitro. Drug delivery effectiveness in vivo not demonstrated. Scalability of synthesis not addressed. Comparison to established liposomal drug delivery systems not detailed."},{"rthcId":"RPEP-05437","title":"Effect of oral semaglutide on the pharmacokinetics of thyroxine after dosing of levothyroxine and the influence of co-administered tablets on the pharmacokinetics of oral semaglutide in healthy subjects: an open-label, one-sequence crossover, single-center, multiple-dose, two-part trial.","authors":"Hauge, Camilla; Breitschaft, Astrid; Hartoft-Nielsen, Marie-Louise; Jensen, Simon; Bækdal, Tine A","year":2021,"journal":"Expert opinion on drug metabolism & toxicology, 17(9), 1139-1148","doi":"10.1080/17425255.2021.1955856","pmid":"34289755","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05438","title":"Humanin: A mitochondrial-derived peptide in the treatment of apoptosis-related diseases.","authors":"Hazafa, Abu; Batool, Ammara; Ahmad, Saeed; Amjad, Muhammad; Chaudhry, Sundas Nasir; Asad, Jamal; Ghuman, Hasham Feroz; Khan, Hafiza Madeeha; Naeem, Muhammad; Ghani, Usman","year":2021,"journal":"Life sciences, 264, 118679","doi":"10.1016/j.lfs.2020.118679","pmid":"33130077","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05439","title":"Structure-based derivation and optimization of YAP-like coactivator-derived peptides to selectively target TEAD family transcription factors by hydrocarbon stapling and cyclization.","authors":"He, Bo; Wu, Tao; He, Ping; Lv, Fenglin; Liu, Hongxiang","year":2021,"journal":"Chemical biology & drug design, 97(6), 1129-1136","doi":"10.1111/cbdd.13813","pmid":"33283479","tags":["cyclic-peptides","cancer","peptide-design"],"studyType":"Computational & Biophysical Study","evidenceStrength":"Preliminary","keyFinding":"Systematic binding profiles created for 9 peptides (5 α-helical, 4 Ω-loop) from 8 coactivators against all 4 TEADs. Hydrocarbon stapling and cyclization improved binding affinity without altering TEAD recognition specificity.","whyItMatters":"Different cancers involve different TEAD proteins. Having a library of optimized peptides targeting each TEAD specifically enables precision cancer therapy — matching the right peptide to the right tumor type.","specificNumbers":"4 TEAD targets; 8 coactivator sources; 9 peptides (5 helical, 4 loop); stapling/cyclization improved affinity; selectivity unchanged","methodology":"Computational structural, energetic, and dynamic investigations. Systematic TEAD-coactivator interaction profiling. Hydrocarbon stapling of α-helical peptides and disulfide cyclization of Ω-loop peptides. Binding affinity analysis.","limitations":"Computational study with structural modeling — experimental binding validation needed. No cell-based or in vivo anti-cancer activity tested. Manufacturing multiple specialized peptides may be complex."},{"rthcId":"RPEP-05440","title":"GLP-2 Is Locally Produced From Human Islets and Balances Inflammation Through an Inter-Islet-Immune Cell Crosstalk.","authors":"He, Wei; Rebello, Osmond D; Henne, Antonia; Nikolka, Fabian; Klein, Thomas; Maedler, Kathrin","year":2021,"journal":"Frontiers in endocrinology, 12, 697120","doi":"10.3389/fendo.2021.697120","pmid":"34290670","tags":["glp-2","diabetes","inflammation","pancreatic-islets"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Human islets actively secrete GLP-2 under normal conditions, and this secretion increases under diabetic stress conditions (high glucose/palmitate, inflammatory cytokines, and LPS). The DPP-4 inhibitor linagliptin markedly potentiated GLP-2 levels by preventing its breakdown.\n\nGLP-2 receptor (GLP-2R) mRNA was found in islets from all 10 donors tested, though expression was low and decreased under inflammatory conditions. Activating the GLP-2R with teduglutide had no effect on insulin secretion or beta cell function, but it specifically dampened macrophage-dependent inflammatory markers (IL1B and IL10) while leaving macrophage-independent cytokines (IL6, IL8, TNF) unaffected. The GLP-2R antagonist GLP-2(3-33) reversed this anti-inflammatory effect, confirming it was receptor-mediated. Conditioned media from teduglutide-treated islets also reduced M1-like (pro-inflammatory) polarization of macrophages, including lower production of itaconate and succinate — metabolic markers of activated inflammatory macrophages.","whyItMatters":"Chronic low-grade inflammation is increasingly recognized as a central driver of beta cell failure in type 2 diabetes. This study reveals that the pancreas has its own local GLP-2 system that may serve as a built-in anti-inflammatory defense for islets. The finding also has implications for DPP-4 inhibitor therapy — these drugs (like linagliptin) prevent the breakdown of both GLP-1 and GLP-2, meaning their pancreatic benefits may partly come from enhanced local GLP-2 signaling, not just GLP-1. This opens a new dimension of understanding how incretin-based diabetes drugs actually work.","specificNumbers":"10 donors; GLP-2 secretion increased by stress; linagliptin potentiated; teduglutide reduced IL1B/IL10; reduced M1 polarization; no insulin secretion effect","methodology":"Isolated human islets from 10 non-diabetic donors exposed to diabetogenic conditions (high glucose, palmitate, cytokines, LPS) with/without linagliptin, teduglutide, and GLP-2(3-33) antagonist. GLP-2 secretion, GLP-2R expression, insulin secretion, cytokine expression, and macrophage polarization measured.","limitations":"This is an in vitro study using isolated human islets — not a study in living patients. Only 10 donors were used, and GLP-2R expression was low, raising questions about how physiologically significant the receptor signaling is. The anti-inflammatory effect operated through an indirect mechanism (islet-macrophage crosstalk), making it more complex and harder to predict in vivo. No animal models or clinical data were included. The study doesn't determine whether GLP-2's anti-inflammatory effect actually protects beta cells from destruction over time."},{"rthcId":"RPEP-05441","title":"Immunization with short peptide particles reveals a functional CD8+ T-cell neoepitope in a murine renal carcinoma model.","authors":"He, Xuedan; Zhou, Shiqi; Dolan, Melissa; Shi, Yuhao; Wang, Jianxin; Quinn, Breandan; Jahagirdar, Dushyant; Huang, Wei-Chiao; Tsuji, Moriya; Pili, Roberto; Ito, Fumito; Ortega, Joaquin; Abrams, Scott I; Ebos, John M L; Lovell, Jonathan F","year":2021,"journal":"Journal for immunotherapy of cancer, 9(12)","doi":"10.1136/jitc-2021-003101","pmid":"34862254","tags":["cancer","peptide-delivery","immune-function"],"studyType":"Preclinical Animal Study","evidenceStrength":"Moderate","keyFinding":"Single neoepitope Nes2LR as short peptide nanoparticle vaccine prevented tumor growth and eradicated disease in subcutaneous, lung metastasis, and orthotopic renal carcinoma models at doses orders of magnitude lower than other adjuvants. Synergized with checkpoint blockade.","whyItMatters":"Most neoepitope vaccines require complex long peptides or mRNA delivery. This shows that simple short peptides converted to nanoparticles can achieve powerful anti-tumor immunity at ultra-low doses — potentially making cancer vaccines simpler and cheaper.","specificNumbers":"20 candidates; 1 functional (Nes2LR); worked in 20/60-plex; orders of magnitude lower dose; eradicated tumors in 3 models; synergized with checkpoint blockade","methodology":"Preclinical study. RENCA murine renal carcinoma. 20 MHC-I neoepitopes predicted by sequencing. Screened as immunogenic nanoparticles. Nes2LR tested in subcutaneous, experimental lung metastasis, and orthotopic tumor models. Combination with immune checkpoint blockade.","limitations":"Mouse renal carcinoma model — human tumors are more heterogeneous. Only 1 of 20 predicted neoepitopes was functionally active. Human MHC diversity makes neoepitope prediction more challenging. No human clinical data."},{"rthcId":"RPEP-05442","title":"Management of post-transplant diabetes: immunosuppression, early prevention, and novel antidiabetics.","authors":"Hecking, Manfred; Sharif, Adnan; Eller, Kathrin; Jenssen, Trond","year":2021,"journal":"Transplant international : official journal of the European Society for Organ Transplantation, 34(1), 27-48","doi":"10.1111/tri.13783","pmid":"33135259","tags":["glp-1","diabetes","kidney","clinical-trials"],"studyType":"Review","evidenceStrength":"Low","keyFinding":"Retrospective data suggest GLP-1RAs are safe in PTDM with no major concerns, particularly suitable for obese transplant recipients. SGLT2is show moderate to low antihyperglycemic efficacy depending on kidney function. Collaborative trials across transplant disciplines are needed.","whyItMatters":"PTDM affects up to 30% of organ transplant recipients and increases cardiovascular risk. GLP-1 drugs that control blood sugar AND help with the weight gain from immunosuppressive drugs could significantly improve long-term transplant outcomes.","specificNumbers":"SGLT2i: moderate glucose lowering, kidney-dependent; GLP1-RA: case reports only; tacrolimus-linked insulin reduction; mostly kidney transplant data","methodology":"Narrative review of PTDM management strategies including immunosuppression modification, lifestyle intervention, early insulin, SGLT2is, and GLP-1RAs. Review of recent safety and efficacy data in transplant populations.","limitations":"Review based primarily on retrospective case reports for GLP-1RAs in transplant patients. No randomized controlled trials completed. Drug interactions with immunosuppressants not fully characterized. Mostly kidney transplant data."},{"rthcId":"RPEP-05443","title":"Bioinspired short peptide hydrogel for versatile encapsulation and controlled release of growth factor therapeutics.","authors":"Hiew, Shu Hui; Wang, Jun Kit; Koh, Kenrick; Yang, Haibo; Bacha, Abbas; Lin, Junquan; Yip, Yun Sheng; Vos, Marcus Ivan Gerard; Chen, Liyan; Sobota, Radoslaw M; Tan, Nguan Soon; Tay, Chor Yong; Miserez, Ali","year":2021,"journal":"Acta biomaterialia, 136, 111-123","doi":"10.1016/j.actbio.2021.09.023","pmid":"34551327","tags":["peptide-delivery","wound-healing","peptide-design"],"studyType":"In Vitro Study","evidenceStrength":"Preliminary","keyFinding":"Bio-inspired short peptide hydrogels demonstrated versatile encapsulation of diverse bioactive molecules with controlled release properties, applicable to drug delivery and tissue engineering.","whyItMatters":"Getting drugs to release at the right speed and location is a major pharmaceutical challenge. Peptide hydrogels that can be tuned for different cargo and release rates could improve many existing medications.","specificNumbers":"8-amino-acid GV8 peptide; one-pot formulation; concentration-dependent G'; controlled secretome release; preserved activity; promoted cell migration","methodology":"In vitro study. Design and characterization of self-assembling peptide hydrogels. Encapsulation of various bioactive molecules. Release kinetics measured. Material properties characterized.","limitations":"In vitro characterization. In vivo drug delivery performance not assessed. Specific therapeutic applications not tested. Long-term stability under physiological conditions unclear."},{"rthcId":"RPEP-05444","title":"Durability of Linear Small-Intestinal Growth Following Treatment Discontinuation of Long-Acting Glucagon-Like Peptide 2 (GLP-2) Analogues.","authors":"Hinchliffe, Tierah; Pauline, Mirielle L; Wizzard, Pamela R; Nation, Patrick N; Brubaker, Patricia; Campbell, Jhenielle R; Kim, Yunji; Dimitriadou, Violetta; Wales, Paul W; Turner, Justine M","year":2021,"journal":"JPEN. Journal of parenteral and enteral nutrition, 45(7), 1466-1474","doi":"10.1002/jpen.2053","pmid":"33241564","tags":["glp-1","gut-healing"],"studyType":"Preclinical Animal Study","evidenceStrength":"Moderate","keyFinding":"GLP-2 analogues increased intestinal length by day 7 (p=0.005), maintained (teduglutide) or further increased (apraglutide) at day 14 after cessation (p<0.001). Mucosal adaptation (villus hyperplasia) was not durable after treatment cessation.","whyItMatters":"Lasting intestinal growth means GLP-2 treatment courses could permanently improve gut capacity in infants with short bowel syndrome, potentially freeing them from lifelong IV nutrition — a transformative outcome.","specificNumbers":"P=0.005 length at day 7; P<0.001 at day 14; villus hyperplasia P=0.081 at day 14; teduglutide 0.05mg/kg BID; apraglutide 5mg/kg twice weekly","methodology":"Neonatal short-bowel piglet model. Three groups: saline control, teduglutide (0.05mg/kg twice daily × 7 days), apraglutide (5mg/kg twice weekly × 7 days). Endpoints at day 7 and day 14 (7 days after cessation). Intestinal length, weight, histology, and mucosal gene expression measured.","limitations":"Neonatal piglet model — human neonatal intestine may respond differently. Short observation period (14 days). Only two GLP-2 analogues tested. Molecular mechanisms of lasting growth not identified. Long-term outcomes and functional absorption capacity not assessed."},{"rthcId":"RPEP-05445","title":"Tumor Activated Cell Penetrating Peptides to Selectively Deliver Immune Modulatory Drugs.","authors":"Hingorani, Dina V; Camargo, Maria F; Quraishi, Maryam A; Adams, Stephen R; Advani, Sunil J","year":2021,"journal":"Pharmaceutics, 13(3)","doi":"10.3390/pharmaceutics13030365","pmid":"33801967","tags":["cell-penetrating","cancer","peptide-delivery","immune-function"],"studyType":"Preclinical Animal Study","evidenceStrength":"Moderate","keyFinding":"ACPP-resiquimod conjugate achieved >1,000-fold greater tumor tissue concentration than surrounding normal tissue after systemic delivery. Therapeutic efficacy matched localized free resiquimod in syngeneic murine tumors. Dual enzymatic activation: MMP-2/9 cleavage + cathepsin B release.","whyItMatters":"Many powerful immune drugs are too toxic for systemic use. This precision peptide delivery achieves the impossible — systemic injection with localized tumor effects — potentially making potent immune modulators safe enough for clinical cancer therapy.","specificNumbers":">1,000-fold tumor selectivity; MMP 2/9 activated; cathepsin B release; systemic = local efficacy","methodology":"Preclinical study. Activatable CPP designed with MMP-2/9 cleavage site and cathepsin B-cleavable linker for resiquimod. Tissue biodistribution measured. Anti-tumor efficacy tested in syngeneic murine tumor models with systemic delivery.","limitations":"Mouse tumor models only. MMP expression varies between human tumors. Drug payload limited to resiquimod in this study. Manufacturing complexity of peptide-drug conjugates. Long-term safety not assessed."},{"rthcId":"RPEP-05446","title":"Heterologous Prime-Boost Vaccination with a Peptide-Based Vaccine and Viral Vector Reshapes Dendritic Cell, CD4+ and CD8+ T Cell Phenotypes to Improve the Antitumor Therapeutic Effect.","authors":"Hofer, Tamara; Rossi, Matteo; Carboni, Susanna; Di Berardino Besson, Wilma; von Laer, Dorothee; Wollmann, Guido; Derouazi, Madiha; Santiago-Raber, Marie-Laure","year":2021,"journal":"Cancers, 13(23)","doi":"10.3390/cancers13236107","pmid":"34885215","tags":["cancer","immune-function","peptide-delivery"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"A heterologous prime-boost vaccination strategy — combining a peptide-based vaccine (KISIMA-TAA) with a viral vector boost (VSV-GP-TAA) — generated potent antitumor immunity in two distinct mouse tumor models. In the cold TC-1 tumor model (HPV-associated), the combination turned immune-excluded tumors into hot, inflamed tumors by recruiting cross-presenting dendritic cells, increasing functional antigen-specific CD8+ killer T-cells, and polarizing CD4+ T-cells toward an antitumor Th1 phenotype.\n\nIn the already immune-infiltrated MC-38 model, the combination markedly prolonged overall survival. Multi-epitope vaccines induced high frequencies of T-cells targeting multiple tumor antigens simultaneously. The treatment also reduced immunosuppressive regulatory T-cells in tumors.","whyItMatters":"One of the biggest challenges in cancer immunotherapy is that many tumors are 'cold' — they exclude immune cells and don't respond to checkpoint inhibitors. This study shows that a peptide vaccine prime followed by a viral vector boost can convert cold tumors into hot, inflamed tumors susceptible to immune attack. If this approach translates to humans, it could extend the benefits of immunotherapy to the many cancer types that currently don't respond.","specificNumbers":"2 tumor models tested · Cold TC-1 tumors converted to hot · MC-38 survival markedly prolonged · Cross-presenting DCs recruited · Tregs reduced · Multi-epitope antigen-specific responses induced","methodology":"Mouse tumor models: TC-1 (cold, HPV antigen) and MC-38 (hot, neoantigen-expressing). Mice received a KISIMA peptide vaccine prime followed by VSV-GP viral vector boost, both expressing tumor-associated antigens. Immune cell profiling by flow cytometry analyzed dendritic cells, CD4+ and CD8+ T-cells, and regulatory T-cells in tumors and tumor-draining lymph nodes. Tumor growth and overall survival were measured.","limitations":"Mouse models only — TC-1 and MC-38 are well-characterized but don't represent the full complexity of human cancers. No comparison with checkpoint inhibitors alone was performed. The viral vector component introduces manufacturing complexity and potential safety considerations. Multi-epitope vaccine immunogenicity may differ in human HLA-diverse populations."},{"rthcId":"RPEP-05447","title":"Lactoferricin-Derived L5a Cell-Penetrating Peptide for Delivery of DNA into Cells.","authors":"Holl, Natalie J; Dey, Moumita; Huang, Yue-Wern; Chiou, Shiow-Her; Lee, Han-Jung","year":2021,"journal":"Methods in molecular biology (Clifton, N.J.), 2211, 113-121","doi":"10.1007/978-1-0716-0943-9_9","pmid":"33336274","tags":["cell-penetrating","antimicrobial-peptides","peptide-delivery"],"studyType":"Methods Paper","evidenceStrength":"Preliminary","keyFinding":"L5a (RRWQW), derived from bovine lactoferricin, is one of the smallest CPPs known and delivers plasmid DNA into mammalian cells and nuclei via direct membrane translocation.","whyItMatters":"Smaller cell-penetrating peptides are potentially safer, cheaper, and less immunogenic than larger ones. A 5-amino-acid peptide that delivers genes to the nucleus is remarkably efficient for its size.","specificNumbers":"5 amino acids RRWQW; derived from bovine lactoferricin; direct membrane translocation; nuclear delivery confirmed","methodology":"Methods paper. Noncovalent L5a/DNA complex formation and gel retardation assay. Cell transfection and fluorescent reporter gene detection by microscopy. Mechanism studies for direct membrane translocation.","limitations":"Methods paper with limited scope. Transfection efficiency not compared to established methods. No in vivo data. Only plasmid DNA delivery tested. Cell types used not specified in abstract."},{"rthcId":"RPEP-05448","title":"Constipation Caused by Anti-calcitonin Gene-Related Peptide Migraine Therapeutics Explained by Antagonism of Calcitonin Gene-Related Peptide's Motor-Stimulating and Prosecretory Function in the Intestine.","authors":"Holzer, Peter; Holzer-Petsche, Ulrike","year":2021,"journal":"Frontiers in physiology, 12, 820006","doi":"10.3389/fphys.2021.820006","pmid":"35087426","tags":["neuropeptides","pain","side-effects","gut-healing"],"studyType":"Review","evidenceStrength":"Moderate","keyFinding":"Constipation from anti-CGRP migraine therapeutics results from blocking CGRP's physiological role in maintaining intestinal peristalsis, ion/water secretion, and transit through both extrinsic and enteric nerve pathways.","whyItMatters":"Over 50% of patients on anti-CGRP drugs experience constipation. Understanding why helps clinicians manage this side effect and set proper expectations for patients starting these medications.","specificNumbers":">50% constipation rate; CGRP drives peristalsis; CGRP drives secretion; CGRP accelerates transit; causes diarrhea exogenously","methodology":"Narrative review of CGRP's pharmacological actions in the digestive tract, including enteric nervous system function, peristalsis, secretion, and transit studies in animals and humans.","limitations":"Narrative review with no original data. The >50% constipation rate is from real-world surveys, not randomized trials. Individual variation in constipation severity is not well characterized. Management strategies for the constipation are not reviewed."},{"rthcId":"RPEP-05449","title":"Comparative Antimicrobial Activity of Hp404 Peptide and Its Analogs against Acinetobacter baumannii.","authors":"Hong, Min Ji; Kim, Min Kyung; Park, Yoonkyung","year":2021,"journal":"International journal of molecular sciences, 22(11)","doi":"10.3390/ijms22115540","pmid":"34073939","tags":["venom-peptides","antimicrobial-peptides","infection"],"studyType":"In Vitro Study","evidenceStrength":"Preliminary","keyFinding":"Hp1404 analog peptides showed reduced cytotoxicity, enhanced activity against MDR A. baumannii, dual membrane disruption (outer + cytoplasmic), and improved biofilm inhibition at low concentrations compared to parent peptide.","whyItMatters":"MDR A. baumannii is classified as a critical priority pathogen by WHO. Peptides that kill it through membrane disruption and biofilm prevention address an urgent unmet medical need where traditional antibiotics are failing.","specificNumbers":"14 C-terminal residues modified; active against MDR A. baumannii; membrane permeabilization (NPN, DiSC3-5); biofilm inhibition; lower cytotoxicity","methodology":"In vitro study. Amino acid substitution at 14 C-terminal positions of scorpion peptide Hp1404. Antimicrobial testing against gram-positive and gram-negative bacteria. Cytotoxicity assessment. Membrane permeabilization (NPN uptake, DiSC3-5). Biofilm inhibition assays.","limitations":"In vitro testing only. No animal infection model data. Peptide stability in biological fluids not assessed. Manufacturing scalability and cost not addressed."},{"rthcId":"RPEP-05450","title":"New Anti-CGRP Medications in the Treatment of Vestibular Migraine.","authors":"Hoskin, Justin L; Fife, Terry D","year":2021,"journal":"Frontiers in neurology, 12, 799002","doi":"10.3389/fneur.2021.799002","pmid":"35153979","tags":["neuropeptides","pain"],"studyType":"Retrospective Case Series","evidenceStrength":"Low","keyFinding":"84% (21/25) of vestibular migraine patients showed some improvement with anti-CGRP medications, with 60% (15/25) reporting moderate to significant improvement.","whyItMatters":"Vestibular migraine is underdiagnosed and undertreated. If anti-CGRP drugs help with the vertigo and dizziness components (not just headache), this expands their usefulness significantly.","specificNumbers":"28 patients; 25 evaluable; 84% some improvement; 60% moderate-significant; 4 anti-CGRP drugs used","methodology":"Retrospective chart review. 28 vestibular migraine patients prescribed CGRP medications (January 2016-July 2020). 25 had follow-up. Improvement categorized as significant, moderate, mild, or none.","limitations":"Retrospective design with no control group. Small sample (25 evaluable). Subjective improvement ratings. Mixed drug types used. Cannot separate drug effect from placebo or natural improvement."},{"rthcId":"RPEP-05451","title":"Depletion of Alpha-Melanocyte-Stimulating Hormone Induces Insatiable Appetite and Gains in Energy Reserves and Body Weight in Zebrafish.","authors":"Hsieh, Yang-Wen; Tsai, Yi-Wen; Lai, Hsin-Hung; Lai, Chi-Yu; Lin, Chiu-Ya; Her, Guor Mour","year":2021,"journal":"Biomedicines, 9(8)","doi":"10.3390/biomedicines9080941","pmid":"34440144","tags":["melanotan","weight-loss","receptor-signaling","hormone-optimization"],"studyType":"Preclinical Animal Study (Zebrafish)","evidenceStrength":"Moderate","keyFinding":"α-MSH mutant zebrafish showed hyperphagic phenotypes and weight gain with upregulated orexigenic genes (NPY, AgRP2, pmch, hcrt) and altered anorexigenic genes. Melanotan II injection completely rescued the hyperphagia, confirming α-MSH as a key appetite regulator.","whyItMatters":"This proves α-MSH is a critical appetite suppressor, not just a correlate. The complete rescue by Melanotan II validates melanocortin receptor agonists as a legitimate approach to treating obesity — a billion-dollar pharmaceutical target.","specificNumbers":"7aa and 8aa MSH deletions; hyperphagia + weight gain; 9 genes analyzed; Melanotan II fully rescued; altered energy expenditure","methodology":"Genetic engineering of zebrafish α-MSH mutants (7aa and 8aa deletions) retaining other Pomc-derived peptides. Gene expression analysis of 9 appetite genes. Hindbrain ventricle injection of synthetic α-MSH analog and Melanotan II. Metabolic rate assessment by Alamar Blue assay.","limitations":"Zebrafish model — appetite regulation may differ from mammals. Hindbrain injection is not a practical delivery route. Melanotan II has side effects (skin darkening, nausea) that limit its clinical use. Long-term metabolic effects not assessed."},{"rthcId":"RPEP-05452","title":"Inhibition of melanoma by survivin-specific lymphocytes combined with CCL17 and granulocyte-macrophage colony-stimulating factor in a mouse syngeneic model.","authors":"Huang, Lan; Chen, Guisi; Chen, Ying; Wu, Wanwen; Tao, Changli; Shao, Hongwei; Huang, Shulin; Shen, Han","year":2021,"journal":"Anti-cancer drugs, 32(2), 138-147","doi":"10.1097/CAD.0000000000000978","pmid":"32932278","tags":["cancer","immune-function"],"studyType":"Preclinical Animal Study","evidenceStrength":"Preliminary","keyFinding":"Survivin-specific cytotoxic T lymphocytes combined with CCL17 and GM-CSF gene expression in B16F10 melanoma cells produced superior tumor growth inhibition with increased tumor necrosis and lymphocyte infiltration.","whyItMatters":"Survivin is overexpressed in many cancers, making it a broadly applicable vaccine target. Combining a peptide vaccine with immune-attracting signals could improve cancer immunotherapy outcomes.","specificNumbers":"Triple combo best; increased necrosis; increased lymphocyte infiltration; CTL+CCL17 strongest in vitro","methodology":"Mouse melanoma model. Survivin epitope prediction (BIMAS, SYFPEITHI), peptide vaccine synthesis, and CTL induction from immunized mouse spleens. B16F10 cells engineered to express CCL17 and/or GM-CSF. In vitro killing assays and in vivo tumor growth measurement. HE staining and immunohistochemistry.","limitations":"Mouse model only (B16F10 melanoma). Engineered tumor cells are artificial. In clinical settings, tumors would need to be modified or the immune signals delivered separately. Survivin peptide restricted to specific HLA types. No survival data reported."},{"rthcId":"RPEP-05453","title":"Design of acid-activated cell-penetrating peptides with nuclear localization capacity for anticancer drug delivery.","authors":"Huang, Sujie; Zhu, Zhongwen; Jia, Bo; Zhang, Wei; Song, Jingjing","year":2021,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 27(10), e3354","doi":"10.1002/psc.3354","pmid":"34101293","tags":["cell-penetrating","cancer","peptide-delivery","peptide-design"],"studyType":"In Vitro Study","evidenceStrength":"Preliminary","keyFinding":"HNLS-3 displayed pH-dependent cellular uptake, endosomal escape, and nuclear localization. HNLS-3-CPT conjugate showed enhanced cytotoxicity and selectivity compared to free CPT.","whyItMatters":"Many cancer drugs work in the nucleus but can't get there efficiently. A peptide that activates in acidic tumors AND delivers drugs to the nucleus solves two delivery problems simultaneously.","specificNumbers":"6 His residues; PFVYLI sequence; NLS; enhanced CPT cytotoxicity; improved selectivity; pH-dependent activation","methodology":"Peptide design combining 6 histidine residues, hydrophobic sequence PFVYLI, and nuclear localization sequence. pH-dependent uptake, endosomal escape, and nuclear localization assessed. Cytotoxicity of peptide-drug conjugate versus free drug measured.","limitations":"In vitro cancer cell study only. No animal tumor models tested. Peptide stability in blood and biodistribution unknown. Manufacturing complexity of peptide-drug conjugates."},{"rthcId":"RPEP-05454","title":"Intranasal oxytocin in the treatment of autism spectrum disorders: A multilevel meta-analysis.","authors":"Huang, Yi; Huang, Xin; Ebstein, Richard P; Yu, Rongjun","year":2021,"journal":"Neuroscience and biobehavioral reviews, 122, 18-27","doi":"10.1016/j.neubiorev.2020.12.028","pmid":"33400920","tags":["oxytocin","nasal-peptides","clinical-trials"],"studyType":"Meta-Analysis","evidenceStrength":"Moderate","keyFinding":"Meta-analysis of 28 studies (N=726 ASD patients) found oxytocin had beneficial effects on social functioning but no strong evidence for improvement in non-social domains. Multilevel meta-analytic model used.","whyItMatters":"Social impairment is the core disability of ASD with no approved pharmacological treatment. This meta-analysis provides the strongest evidence to date that oxytocin specifically addresses this deficit, supporting its development as a targeted ASD therapy.","specificNumbers":"28 studies; 726 ASD patients; improved social functioning; no non-social improvement; multilevel model","methodology":"Systematic literature search. 28 studies included: randomized controlled trials, single/double-blind, open-label, and single-arm studies. 726 ASD patients total. Multilevel meta-analytic model to account for study heterogeneity.","limitations":"Included both controlled and uncontrolled studies (though analyzed separately). High heterogeneity between studies. Varied dosing, duration, and outcome measures. Many studies were small. Effect sizes were modest."},{"rthcId":"RPEP-05455","title":"Stimulation of endogenous pulsatile growth hormone secretion by activation of growth hormone secretagogue receptor reduces the fat accumulation and improves the insulin sensitivity in obese mice.","authors":"Huang, Zhengxiang; Lu, Xuehan; Huang, Lili; Zhang, Chunhong; Veldhuis, Johannes D; Cowley, Michael A; Chen, Chen","year":2021,"journal":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 35(1), e21269","doi":"10.1096/fj.202001924RR","pmid":"33368660","tags":["ghrp","weight-loss","hormone-optimization","liver"],"studyType":"Preclinical Animal Study","evidenceStrength":"Moderate","keyFinding":"Hexarelin (10.56 mcg/day continuous infusion) increased pulsatile GH secretion in MC4RKO obese mice, reducing visceral fat and liver triglycerides while improving insulin sensitivity without altering IGF-1 or insulin levels.","whyItMatters":"Obesity reduces GH secretion, creating a vicious cycle of more fat storage. Restoring pulsatile GH release with a small peptide could break this cycle without the side effects of direct GH injection (which raises IGF-1 and can worsen insulin resistance).","specificNumbers":"10.56 mcg/day hexarelin; 3-4 weeks; increased pulsatile GH; reduced visceral fat; reduced liver TG; improved insulin sensitivity; no IGF-1/insulin change","methodology":"MC4R knockout obese mice pair-fed and infused continuously with hexarelin (10.56 mcg/day) or vehicle via osmotic pump for 3-4 weeks. Pulsatile GH secretion, lipolysis, lipid oxidation, de novo lipogenesis, insulin sensitivity, glucose tolerance, and GH signaling gene expression measured.","limitations":"Mouse model (MC4RKO, not typical human obesity). Pair-fed design controls for food intake but limits ecological validity. Continuous hexarelin infusion via pump is not practical for human use. Only 3-4 weeks of treatment. Hexarelin is not FDA-approved."},{"rthcId":"RPEP-05456","title":"Sotatercept for the Treatment of Pulmonary Arterial Hypertension.","authors":"Humbert, Marc; McLaughlin, Vallerie; Gibbs, J Simon R; Gomberg-Maitland, Mardi; Hoeper, Marius M; Preston, Ioana R; Souza, Rogerio; Waxman, Aaron; Escribano Subias, Pilar; Feldman, Jeremy; Meyer, Gisela; Montani, David; Olsson, Karen M; Manimaran, Solaiappan; Barnes, Jennifer; Linde, Peter G; de Oliveira Pena, Janethe; Badesch, David B","year":2021,"journal":"The New England journal of medicine, 384(13), 1204-1215","doi":"10.1056/NEJMoa2024277","pmid":"33789009","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05457","title":"Glucagon-like peptide 1 receptor (GLP-1R) agonist relieved asthmatic airway inflammation via suppression of NLRP3 inflammasome activation in obese asthma mice model.","authors":"Hur, Jung; Kang, Ji Young; Kim, Young Kyoon; Lee, Sook Young; Lee, Hwa Young","year":2021,"journal":"Pulmonary pharmacology & therapeutics, 67, 102003","doi":"10.1016/j.pupt.2021.102003","pmid":"33588055","tags":["glp-1","inflammation","respiratory","weight-loss"],"studyType":"Preclinical Animal Study","evidenceStrength":"Preliminary","keyFinding":"GLP-1R agonist induced weight loss, suppressed eosinophilic inflammation, reduced AHR, decreased IL-4/5/33, and inhibited NLRP3 inflammasome activation (reduced NLRP3, caspase-1, IL-1β) in lung tissues of obese asthmatic mice.","whyItMatters":"Obese asthmatics respond poorly to standard asthma drugs. A GLP-1 drug that addresses both obesity and airway inflammation through a specific mechanism (NLRP3 inhibition) could provide dual-target therapy for this difficult-to-treat patient group.","specificNumbers":"8 wk HFD; 4 wk GLP-1R agonist; reduced AHR; reduced eosinophils; suppressed NLRP3/caspase-1/IL-1beta; reduced IL-4/IL-5/IL-33","methodology":"Animal study. High-fat diet (8 weeks) + OVA sensitization/challenge (7 weeks) in mice. GLP-1R agonist IP injection 5x/week for 4 weeks. AHR measurement. BALF and lung tissue cytokine analysis. NLRP3 inflammasome activity assessment. Histology.","limitations":"Mouse model with OVA-induced allergic asthma — may not replicate all aspects of human obese asthma. GLP-1 drug effects may be partly secondary to weight loss. Specific GLP-1R agonist not named in abstract."},{"rthcId":"RPEP-05458","title":"Acute Oral Calcium Suppresses Food Intake Through Enhanced Peptide-YY Secretion Mediated by the Calcium-Sensing Receptor in Rats.","authors":"Igarashi, Akiho; Ogasawara, Shono; Takagi, Ryo; Okada, Kazufumi; Ito, Yoichi M; Hara, Hiroshi; Hira, Tohru","year":2021,"journal":"The Journal of nutrition, 151(5), 1320-1328","doi":"10.1093/jn/nxab013","pmid":"33693689","tags":["bioactive-food-peptides","weight-loss","receptor-signaling"],"studyType":"Preclinical Animal Study","evidenceStrength":"Moderate","keyFinding":"Oral CaCl2 suppressed food intake by ~20% through CaSR-mediated PYY secretion, with the effect abolished by PYY receptor or CaSR antagonists.","whyItMatters":"This reveals a simple dietary mechanism for appetite control. Calcium activates gut sensors that release PYY, a powerful satiety hormone. This could explain why high-calcium diets are associated with less eating.","specificNumbers":"~20% food intake reduction; PYY doubled at 15 min; 4-fold luminal PYY; 150 mg Ca/kg; CaSR and PYY-R antagonists blocked effect","methodology":"Male Sprague Dawley rats. Oral gavage of CaCl2, calcium carbonate, or calcium lactate (150 mg calcium/kg). Food intake measured 0.5-24 hours. Taste aversion test. Plasma PYY, GLP-1, and calcium measured. Portal vein PYY after intraluminal meal + calcium. CaSR agonist and antagonist studies. PYY receptor antagonist studies.","limitations":"Animal study (rats). CaCl2 was more effective than other calcium forms, which may limit practical dietary applications. Only acute effects measured (30 min-24 hr). The satiating dose (150 mg/kg) needs to be translated to human equivalents. Effect was modest (~20%)."},{"rthcId":"RPEP-05459","title":"Phase I studies of peptide vaccine cocktails derived from GPC3, WDRPUH and NEIL3 for advanced hepatocellular carcinoma.","authors":"Ikeda, Masafumi; Okusaka, Takuji; Ohno, Izumi; Mitsunaga, Shuichi; Kondo, Shunsuke; Ueno, Hideki; Morizane, Chigusa; Gemmoto, Kazuto; Suna, Hideaki; Ushida, Yasunori; Furuse, Junji","year":2021,"journal":"Immunotherapy, 13(5), 371-385","doi":"10.2217/imt-2020-0278","pmid":"33525928","tags":["cancer","clinical-trials","immune-function"],"studyType":"Phase I Clinical Trial","evidenceStrength":"Low","keyFinding":"Peptide cocktail vaccines targeting GPC3/WDRPUH/NEIL3 were safe (no DLTs up to 7.1 mg) with disease control rates of 52.9% and 35.7% in advanced HCC, though no tumor shrinkage was observed.","whyItMatters":"Liver cancer has limited treatment options, especially in advanced stages. Peptide vaccines that are safe and can stabilize disease could eventually be combined with checkpoint inhibitors for better results.","specificNumbers":"32 patients; no DLTs to 7.1 mg; 0% CR/PR; 52.9% DCR study 1; 35.7% DCR study 2; HLA-A24 and A02","methodology":"Two phase I dose-escalation studies. Study 1: 18 patients, 3 HLA-A24-restricted peptides. Study 2: 14 patients, 6 HLA-A24/A02-restricted peptides. Advanced HCC patients. Primary endpoint: dose-limiting toxicities. Secondary: tumor response and CTL induction.","limitations":"Phase I (safety-focused, not efficacy). Small sample sizes (18 and 14). No tumor shrinkage observed. HLA-restricted (only works for certain genetic types). No survival data reported. No randomized comparison."},{"rthcId":"RPEP-05460","title":"New Creatinine- and Cystatin C-Based Equations to Estimate GFR without Race.","authors":"Inker, Lesley A; Eneanya, Nwamaka D; Coresh, Josef; Tighiouart, Hocine; Wang, Dan; Sang, Yingying; Crews, Deidra C; Doria, Alessandro; Estrella, Michelle M; Froissart, Marc; Grams, Morgan E; Greene, Tom; Grubb, Anders; Gudnason, Vilmundur; Gutiérrez, Orlando M; Kalil, Roberto; Karger, Amy B; Mauer, Michael; Navis, Gerjan; Nelson, Robert G; Poggio, Emilio D; Rodby, Roger; Rossing, Peter; Rule, Andrew D; Selvin, Elizabeth; Seegmiller, Jesse C; Shlipak, Michael G; Torres, Vicente E; Yang, Wei; Ballew, Shoshana H; Couture, Sara J; Powe, Neil R; Levey, Andrew S","year":2021,"journal":"The New England journal of medicine, 385(19), 1737-1749","doi":"10.1056/NEJMoa2102953","pmid":"34554658","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05461","title":"Role of Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists in Hypoglycemia.","authors":"Ja'arah, Daria; Al Zoubi, Mazhar Salim; Abdelhady, Gamal; Rabi, Firas; Tambuwala, Murtaza M","year":2021,"journal":"Clinical medicine insights. Endocrinology and diabetes, 14, 11795514211051697","doi":"10.1177/11795514211051697","pmid":"34690504","tags":["glp-1","side-effects","diabetes","peptide-safety"],"studyType":"Review","evidenceStrength":"Low","keyFinding":"GLP-1 receptor agonists were proposed to cause hypoglycemia in healthy normoglycemic subjects, challenging the assumption of purely glucose-dependent action. The FDA evaluated all 12 marketed GLP-1 RAs for potential hypoglycemia safety signals. Risk appears dependent on individual factors.","whyItMatters":"With GLP-1 drugs now widely prescribed for both diabetes and weight management in non-diabetic individuals, understanding their hypoglycemia risk — especially in people with normal blood sugar — is critically important for patient safety.","specificNumbers":"12 GLP-1 drugs evaluated by FDA; some evidence of hypoglycemia in normoglycemic subjects; glucose-dependent mechanism questioned","methodology":"Narrative review of clinical studies investigating GLP-1RA hypoglycemic effects, FDA safety evaluations, and adverse effect profiles.","limitations":"Narrative review with conflicting study conclusions. Hypoglycemia definitions vary across studies. Individual risk factors not well characterized. The distinction between clinically significant and asymptomatic hypoglycemia is important."},{"rthcId":"RPEP-05462","title":"Kinetics of pore formation in stearoyl-oleoyl-phosphatidylcholine vesicles by pH sensitive cell penetrating peptide GALA.","authors":"James, Honey Priya; Jadhav, Sameer","year":2021,"journal":"Chemistry and physics of lipids, 241, 105139","doi":"10.1016/j.chemphyslip.2021.105139","pmid":"34560061","tags":["cell-penetrating","peptide-delivery","peptide-design"],"studyType":"Biophysical Study","evidenceStrength":"Preliminary","keyFinding":"Characterized the kinetics of CPP-induced pore formation in stearoyl-oleoyl-phosphatidylcholine vesicles, providing mechanistic data for engineering endosomal escape in liposomal drug delivery.","whyItMatters":"Endosomal escape is the major bottleneck in liposomal drug delivery. Understanding CPP pore formation kinetics enables rational design of more effective delivery systems.","specificNumbers":"Concentration-dependent pore number; pH-activated; GUV confocal microscopy; LUV electron microscopy; kinetics model fitted","methodology":"Biophysical study. CPP-induced pore formation measured in synthetic lipid vesicles using kinetic assays. Membrane composition: stearoyl-oleoyl-phosphatidylcholine.","limitations":"Synthetic vesicle model — biological membranes are more complex. Kinetic parameters may differ in cellular endosomes. Single lipid composition tested."},{"rthcId":"RPEP-05463","title":"Cardiac hypertrophic risk markers of left ventricle and left atrium in chronic heart failure due to aortic and mitral valve disease.","authors":"Jan, Muhammad Ishtiaq; Khan, Riaz Anwar; Khan, Naeem; Mahak, Aisha; Shah, Azhar Ul Haq Ali; Hussain, Syed Tasleem; Kakakhel, Ahaq Ullah; Murtaza, Iram","year":2021,"journal":"Acta radiologica (Stockholm, Sweden : 1987), 62(5), 603-609","doi":"10.1177/0284185120933530","pmid":"32571097","tags":["natriuretic-peptides","cardiovascular"],"studyType":"Cross-Sectional Observational Study","evidenceStrength":"Moderate","keyFinding":"Cardiac hypertrophic risk markers including natriuretic peptides were associated with left ventricular and left atrial hypertrophy in chronic kidney disease patients.","whyItMatters":"Heart disease is the leading killer of CKD patients. Natriuretic peptides as early detection markers could identify patients at risk for heart thickening before symptoms appear, enabling earlier intervention.","specificNumbers":"253 patients; 51 LV hypertrophy; 126 LA enlargement; 76 both; ANP and BNP elevated; positive correlation with cardiac dimensions","methodology":"Clinical observational study measuring cardiac biomarkers and echocardiographic parameters of heart structure in chronic kidney disease patients.","limitations":"Observational study — cannot determine causation. Natriuretic peptide levels can be affected by kidney function itself. Cross-sectional design."},{"rthcId":"RPEP-05464","title":"Stable Gastric Pentadecapeptide BPC 157 as a Therapy for the Disable Myotendinous Junctions in Rats.","authors":"Japjec, Mladen; Horvat Pavlov, Katarina; Petrovic, Andreja; Staresinic, Mario; Sebecic, Bozidar; Buljan, Matko; Vranes, Hrvoje; Giljanovic, Ana; Drmic, Domagoj; Japjec, Miroslav; Prtoric, Andreja; Lovric, Eva; Batelja Vuletic, Lovorka; Dobric, Ivan; Boban Blagaic, Alenka; Skrtic, Anita; Seiwerth, Sven; Predrag, Sikiric","year":2021,"journal":"Biomedicines, 9(11)","doi":"10.3390/biomedicines9111547","pmid":"34829776","tags":[],"studyType":"animal-study","evidenceStrength":"low","keyFinding":"BPC 157 completely restored disabled myotendinous junctions (where muscle connects to tendon) in rats — an injury that does not heal spontaneously. Both intraperitoneal injection (10 µg/kg and 10 ng/kg) and oral administration produced full functional recovery, reversed progressive muscle atrophy, and eliminated the structural defect by day 28-42.\n\nBPC 157 treatment counteracted oxidative stress, normalized NO levels, and modulated eNOS and COX-2 mRNA expression at the injury site. Microscopically, treated rats showed well-oriented recovered tissue with no inflammatory infiltrate by days 28-42, while control rats showed consistently poor outcomes with progressive deterioration.","whyItMatters":"Myotendinous junction injuries — where muscle meets tendon — are among the most difficult musculoskeletal injuries to treat because this transition zone has poor natural healing capacity. Current treatments often require surgery with unpredictable outcomes. If BPC 157's dramatic healing effects in rats could translate to humans, it could transform treatment of common injuries like hamstring avulsions, rotator cuff tears at the muscle-tendon junction, and quadriceps tendon injuries.","specificNumbers":"10 µg/kg and 10 ng/kg doses · IP and oral routes both effective · assessment at 7, 14, 28, 42 days · complete defect disappearance · oral dose: 0.16 µg/mL or 0.16 ng/mL in drinking water","methodology":"Researchers surgically dissected the quadriceps tendon from the quadriceps muscle in rats, creating a myotendinous junction defect. BPC 157 was administered either by intraperitoneal injection (immediately after surgery and daily until sacrifice) or orally in drinking water. Healing was assessed at 7, 14, 28, and 42 days using macroscopic examination, microscopic histology, biomechanical testing, functional assessment, and molecular markers (eNOS, COX-2 mRNA, oxidative stress, NO levels).","limitations":"This is an animal study in rats, and results cannot be directly extrapolated to humans. The study comes from the Sikiric lab in Zagreb, which has produced the majority of BPC 157 research — independent replication by other groups is needed. No human clinical trials of BPC 157 for musculotendinous injuries exist. The specific sample sizes per group are not stated in the abstract."},{"rthcId":"RPEP-05465","title":"Glucagon-like peptide-1, a matter of taste?","authors":"Jensterle, Mojca; DeVries, J Hans; Battelino, Tadej; Battelino, Saba; Yildiz, Bulent; Janez, Andrej","year":2021,"journal":"Reviews in endocrine & metabolic disorders, 22(4), 763-775","doi":"10.1007/s11154-020-09609-x","pmid":"33123893","tags":["glp-1","weight-loss","receptor-signaling"],"studyType":"Systematic Review","evidenceStrength":"Low","keyFinding":"The review establishes several key connections between GLP-1 and taste:\n\n1. GLP-1 is locally synthesized in taste bud cells on the tongue (preclinical evidence)\n2. GLP-1 receptors (GLP-1R) are present on gustatory nerves in close proximity to GLP-1-containing taste bud cells\n3. GLP-1 signaling is specifically involved in the perception of sweet taste\n4. Aging, diabetes, and obesity are all associated with diminished taste and sweet perception\n5. Calorie restriction and bariatric surgery reduce appreciation of sweet foods\n6. GLP-1 receptor agonists modulate food preference in clinical use\n7. Whether GLP-1 drugs directly affect tongue-based taste signaling in humans is currently unknown — the tongue has not been investigated as a clinically relevant target for GLP-1 therapies","whyItMatters":"One of the most commonly reported effects of GLP-1 drugs is changed food preferences — patients say certain foods, especially sweet and fatty ones, become less appealing. This is widely attributed to brain-mediated appetite suppression, but if GLP-1 drugs also change how food actually tastes at the tongue level, it represents a fundamentally different mechanism. Understanding this could help optimize GLP-1 therapies for maximum appetite control and explain why some patients' food preferences change dramatically while others' do not.","specificNumbers":"GLP-1 in taste bud cells; GLP-1R on gustatory nerves; sweet-specific; aging/diabetes/obesity reduce taste; GLP-1 drugs modulate food preference","methodology":"Systematic review using PubMed, Medline, and Embase databases. The Population-Intervention-Comparison-Outcome (PICO) framework was used to identify interventional studies. The review covered preclinical studies of GLP-1 in taste bud biology, clinical data on taste changes in aging/diabetes/obesity, and evidence on food preference modulation by GLP-1 receptor agonists.","limitations":"Most evidence for GLP-1's role in taste perception comes from preclinical (animal) studies. Whether therapeutic doses of GLP-1 drugs reach taste bud cells in the human tongue is unknown. The food preference changes seen clinically could be entirely brain-mediated through reward circuit modulation rather than peripheral taste changes. No interventional human studies have specifically measured taste perception changes in response to GLP-1 drug treatment. The review cannot establish whether the tongue or the brain is the primary site of GLP-1's food preference effects."},{"rthcId":"RPEP-05466","title":"Bovine Lactoferricin Induces Intestinal Epithelial Cell Activation through Phosphorylation of FAK and Paxillin and Prevents Rotavirus Infection.","authors":"Jeong, Ye Young; Lee, Ga Young; Yoo, Yung Choon","year":2021,"journal":"Journal of microbiology and biotechnology, 31(8), 1175-1182","doi":"10.4014/jmb.2106.06044","pmid":"34226406","tags":["antimicrobial-peptides","gut-healing","infection","bioactive-food-peptides"],"studyType":"Preclinical (In Vitro + Animal)","evidenceStrength":"Moderate","keyFinding":"Lfcin-B activated intestinal epithelial cells via FAK/paxillin phosphorylation, with the core 9-amino-acid sequence FKCRRWQWR responsible, and pretreatment prevented rotavirus-induced diarrhea in mice.","whyItMatters":"Rotavirus is a leading cause of severe diarrhea in children worldwide. A milk-derived peptide that both strengthens the gut lining and prevents viral infection could be added to infant formulas or supplements.","specificNumbers":"FKCRRWQWR 9aa core; FAK/paxillin activation; enhanced laminin binding; prevented RV diarrhea; reduced RV titers","methodology":"In vitro: IEC-6 intestinal cell growth, attachment, laminin binding, FAK/paxillin phosphorylation assays. Synthetic peptide mapping of active sequence. In vivo: Lfcin-B pretreatment 1 day before rotavirus infection in mice. Diarrhea assessment and viral titer measurement.","limitations":"Mouse model. Pretreatment (given before infection) is easier to show than treatment after infection starts. IEC-6 cells are rat cells, not human. Specific doses not detailed. Long-term effects not studied."},{"rthcId":"RPEP-05467","title":"Emerging glucagon-like peptide 1 receptor agonists for the treatment of obesity.","authors":"Jepsen, Mathies M; Christensen, Mikkel B","year":2021,"journal":"Expert opinion on emerging drugs, 26(3), 231-243","doi":"10.1080/14728214.2021.1947240","pmid":"34176426","tags":["glp-1","semaglutide","tirzepatide","next-gen-agonists","weight-loss","clinical-trials"],"studyType":"Review","evidenceStrength":"Moderate","keyFinding":"15+ GLP-1-based compounds in clinical obesity development: mono-GLP-1 (semaglutide, PF-0688296, glutazumab), dual (tirzepatide, cotadutide, efinopegdutide, AMG 133), and multi-receptor (CagriSema, HM15211). Semaglutide positioned as the clinical benchmark.","whyItMatters":"The obesity drug market is undergoing a revolution. Understanding the pipeline helps patients and clinicians anticipate future treatment options that may produce even greater weight loss than current drugs.","specificNumbers":">15 compounds; semaglutide benchmark; tirzepatide GLP-1/GIP; cotadutide GLP-1/glucagon; cagrilintide+semaglutide; 1.1B projected obese by 2030","methodology":"Expert review of GLP-1 receptor agonist-based compounds in clinical development for obesity treatment, covering mechanisms, development stages, and clinical pipeline.","limitations":"Pipeline review — many compounds are in early clinical development and may not reach market. Clinical efficacy varies widely between compounds. Long-term safety of multi-hormone combinations unknown."},{"rthcId":"RPEP-05468","title":"Past, present and future of therapeutic strategies against amyloid-β peptides in Alzheimer's disease: a systematic review.","authors":"Jeremic, Danko; Jiménez-Díaz, Lydia; Navarro-López, Juan D","year":2021,"journal":"Ageing research reviews, 72, 101496","doi":"10.1016/j.arr.2021.101496","pmid":"34687956","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05469","title":"Cannabinoid receptor agonists from Conus venoms alleviate pain-related behavior in rats.","authors":"Jergova, Stanislava; Perez, Cecilia; Imperial, Julita S; Gajavelli, Shyam; Jain, Aakangsha; Abin, Adam; Olivera, Baldomero M; Sagen, Jacqueline","year":2021,"journal":"Pharmacology, biochemistry, and behavior, 205, 173182","doi":"10.1016/j.pbb.2021.173182","pmid":"33774007","tags":["venom-peptides","pain","receptor-signaling"],"studyType":"Preclinical Animal Study","evidenceStrength":"Preliminary","keyFinding":"C. textile and C. miles venom subfractions activated CB1 receptor internalization, reduced pain in formalin test and nerve injury model after intrathecal injection, and showed mild to no side effects in CB tetrad assessment. Active components confirmed as peptides.","whyItMatters":"Chronic pain treatment desperately needs alternatives to opioids and cannabis. Peptides that activate cannabinoid receptors without psychoactive effects could provide effective pain relief without the drawbacks of either drug class.","specificNumbers":"C. textile and C. miles active; CB1 internalization; formalin phase 2 reduced; allodynia reduced; peptidergic; mild/no CB tetrad effects","methodology":"Cell-based CB1 receptor internalization assays in HEK293 cells. HPLC fractionation of venom. Intrathecal injection in rodents. Formalin test (inflammatory pain) and peripheral nerve injury model (neuropathic pain). CB tetrad assessment for psychoactive side effects. Proteolytic enzyme treatment to confirm peptide nature.","limitations":"Active peptides not yet fully purified or sequenced. Intrathecal delivery limits practical application. CB1/CB2 selectivity not fully characterized. Small animal models may not predict human responses. Manufacturing challenges for conotoxins."},{"rthcId":"RPEP-05470","title":"Intrinsic, dynamic and effective connectivity among large-scale brain networks modulated by oxytocin.","authors":"Jiang, Xi; Ma, Xiaole; Geng, Yayuan; Zhao, Zhiying; Zhou, Feng; Zhao, Weihua; Yao, Shuxia; Yang, Shimin; Zhao, Zhongbo; Becker, Benjamin; Kendrick, Keith M","year":2021,"journal":"NeuroImage, 227, 117668","doi":"10.1016/j.neuroimage.2020.117668","pmid":"33359350","tags":["oxytocin","nasal-peptides","receptor-signaling"],"studyType":"Neuroimaging Study (fMRI Meta-Analysis)","evidenceStrength":"Moderate","keyFinding":"Oxytocin modulated 54 effective connectivity links among 15 brain regions, increasing both within- and between-network interactions in emotion, reward, salience, attention, and social cognition networks, with sex-dependent effects favoring males.","whyItMatters":"This is the first study showing how oxytocin changes the directional flow of information between brain networks. Understanding these patterns could help optimize oxytocin therapy for autism, schizophrenia, and other social disorders.","specificNumbers":"200 subjects; 54 connectivity links; 15 brain regions; increased amygdala top-down control; enhanced interhemispheric; sex-dependent (males > females)","methodology":"Novel computational framework applied to resting-state fMRI data from randomized placebo-controlled studies (200 healthy subjects total). Effective connectivity analysis of 15 oxytocin-sensitive regions. Temporal dynamics, homotopic interhemispheric connectivity, and sex differences assessed.","limitations":"Resting-state scans (not during social tasks). Healthy subjects, not psychiatric patients. Between-subject design limits individual-level conclusions. Sex differences based on subgroup analysis. Cannot determine if brain changes cause behavioral effects."},{"rthcId":"RPEP-05471","title":"A synthetic peptide AWRK6 ameliorates metabolic associated fatty liver disease: involvement of lipid and glucose homeostasis.","authors":"Jin, Lili; Sun, Yuxin; Li, Yuying; Zhang, Hanyu; Yu, Wenxue; Li, Yiling; Xin, Yi; Alsareii, Saeed Ali; Wang, Qiuyu; Zhang, Dianbao","year":2021,"journal":"Peptides, 143, 170597","doi":"10.1016/j.peptides.2021.170597","pmid":"34118361","tags":["glp-1","liver","antimicrobial-peptides","weight-loss"],"studyType":"Preclinical (Animal + In Vitro)","evidenceStrength":"Preliminary","keyFinding":"AWRK6 (novel GLP-1R agonist from frog AMP) alleviated obesity and hepatic steatosis in HED-induced MAFLD mice, improved lipid and glucose metabolism, and activated PI3K/AKT/AMPK/ACC signaling. Confirmed in human HepG2 fatty liver cell model.","whyItMatters":"MAFLD affects 25%+ of adults globally and has no approved drug. A peptide derived from a natural frog antimicrobial compound that acts through the GLP-1 pathway could represent a novel therapeutic approach, especially given that semaglutide is now being investigated for fatty liver.","specificNumbers":"Frog-derived AWRK6; GLP-1R agonist; reduced obesity/steatosis; PI3K/AKT/AMPK/ACC activated; confirmed in HepG2","methodology":"In vitro and in vivo study. High energy diet-induced MAFLD mice treated with AWRK6 (IP injection). Biochemistry, liver histology, and signaling pathway analysis. Oleic acid-induced HepG2 fatty liver model and insulin sensitivity assays in human cells.","limitations":"Mouse model with IP injection — not a practical clinical route. AWRK6 pharmacokinetics and oral bioavailability not assessed. Comparison to existing GLP-1 drugs not performed. Long-term safety unknown."},{"rthcId":"RPEP-05472","title":"Cytosolic delivery of membrane-penetrating QDs into T cell lymphocytes: implications in immunotherapy and drug delivery.","authors":"Jing, Haoran; Pálmai, Marcell; Saed, Badeia; George, Anne; Snee, Preston T; Hu, Ying S","year":2021,"journal":"Nanoscale, 13(10), 5519-5529","doi":"10.1039/d0nr08362c","pmid":"33688882","tags":["cell-penetrating","peptide-delivery","immune-function"],"studyType":"In Vitro Biophysical Study","evidenceStrength":"Preliminary","keyFinding":"DSS-conjugated quantum dots entered T cells via direct membrane penetration, maintaining monomeric state with only 9% endosomal colocalization, compared to pronounced clustering and endosomal trapping of control QDs.","whyItMatters":"T cell therapies like CAR-T need ways to deliver genes and drugs into T cells. This CPP gets nanoparticles into the cytoplasm without endosome trapping, which is the main barrier to intracellular delivery.","specificNumbers":"9% endosome colocalization; monomeric cytosolic; direct membrane penetration; 3D single-particle tracking; endocytosis inhibition did not block CPP-QDs","methodology":"CdSe/CdZnS quantum dots functionalized with DSS cell-penetrating peptide. Single-particle imaging and tracking in T cells. Endosome colocalization with markers. Endocytosis inhibition experiments. 3D single-particle tracking of membrane penetration.","limitations":"In vitro study. Quantum dots are not therapeutic agents (used as probes). T cell function after QD delivery not assessed. Cytotoxicity of CdSe QDs is a concern. Scalability for clinical T cell engineering not addressed."},{"rthcId":"RPEP-05473","title":"In vitro prediction of in vivo pseudo-allergenic response via MRGPRX2.","authors":"John, Linu M; Dalsgaard, Charlotte M; Jeppesen, Claus B; Conde-Frieboes, Kilian W; Baumann, Katrine; Knudsen, Niels P H; Skov, Per S; Wulff, Birgitte S","year":2021,"journal":"Journal of immunotoxicology, 18(1), 30-36","doi":"10.1080/1547691X.2021.1877375","pmid":"33570451","tags":["peptide-safety","side-effects","injection-technique"],"studyType":"Drug Development/Validation Study","evidenceStrength":"Moderate","keyFinding":"A cell-based MRGPRX2 assay reliably identified peptide compounds causing injection site histamine release and edema in ex vivo skin samples, serving as a replacement for postmortem animal evaluation.","whyItMatters":"Injection site reactions are a common problem in peptide drug development. Being able to screen for this issue in a dish rather than in animals saves time, money, and animal lives while producing results that also predict human reactions.","specificNumbers":"MRGPRX2-mediated; confirmed in human and rodent skin; replaced postmortem eval; significant animal use reduction","methodology":"Peptide drug screening. Subcutaneous injection site evaluation in rats (swelling, histology, mast cell degranulation). MRGPRX2 cell-based assay. Ex vivo human and rodent skin histamine release. Comparison of in vitro predictions with in vivo outcomes.","limitations":"Does not predict all types of injection site reactions (only MRGPRX2-mediated). Some peptide drugs may cause reactions through other mechanisms. In vitro assays may not capture all aspects of the in vivo response. Limited to subcutaneous delivery."},{"rthcId":"RPEP-05474","title":"Drp1-dependent peptide reverse mitochondrial fragmentation, a homeostatic response in Friedreich ataxia.","authors":"Johnson, Joseph; Mercado-Ayón, Elizabeth; Clark, Elisia; Lynch, David; Lin, Hong","year":2021,"journal":"Pharmacology research & perspectives, 9(3), e00755","doi":"10.1002/prp2.755","pmid":"33951329","tags":["cell-penetrating","neuroprotection"],"studyType":"In Vitro Study","evidenceStrength":"Preliminary","keyFinding":"TAT-P110 and SS-31 both reversed Drp1-dependent mitochondrial fragmentation in FRDA cells. TAT-P110 decreased ATP levels (suggesting fragmentation is homeostatic). SS-31 reversed fragmentation without affecting ATP. Both act through the same pathway with different downstream effects.","whyItMatters":"This study reveals a critical nuance for mitochondrial disease therapy: not all mitochondrial \"damage\" should be reversed. Some morphological changes are the cell's way of coping. Therapies must distinguish beneficial compensation from harmful dysfunction.","specificNumbers":"TAT-P110 reversed fragmentation + decreased ATP; SS-31 reversed fragmentation without ATP drop; Drp1-dependent; combination = SS-31 alone","methodology":"In vitro study. Frataxin-knockdown fibroblasts and FRDA patient fibroblasts. Drp1 inhibition by TAT-P110 peptide. Cardiolipin stabilization by SS-31 peptide. Mitochondrial morphology, Drp1 activity, and ATP levels measured. Drug combination testing.","limitations":"In vitro fibroblast study — neuronal and cardiac cells (most affected in FRDA) may respond differently. ATP measurement is one bioenergetic parameter. Long-term effects and functional outcomes not assessed."},{"rthcId":"RPEP-05475","title":"Doping control analysis of small peptides: A decade of progress.","authors":"Judák, Péter; Esposito, Simone; Coppieters, Gilles; Van Eenoo, Peter; Deventer, Koen","year":2021,"journal":"Journal of chromatography. B, Analytical technologies in the biomedical and life sciences, 1173, 122551","doi":"10.1016/j.jchromb.2021.122551","pmid":"33848801","tags":["regulatory","ghrp","hormone-optimization"],"studyType":"Review","evidenceStrength":"Moderate","keyFinding":"Significant progress in LC-MS-based doping control analysis of small peptides over the past decade, enabling reliable detection of growth hormone releasing factors and GnRH analogues among other banned peptide substances.","whyItMatters":"Peptide doping is a growing problem in sports. Without reliable detection methods, athletes can gain unfair advantages using undetectable performance-enhancing peptides. These advances help maintain fair competition.","specificNumbers":"10 years; LC-MS simplified; HRMS standard; metabolite detection; growing prohibited peptide list","methodology":"Review of analytical methodology advances in sports doping control for small peptide detection, focusing on liquid chromatography-mass spectrometry approaches.","limitations":"Review of methods, not clinical outcomes. New designer peptides may still evade detection. Detection windows for some peptides remain short."},{"rthcId":"RPEP-05476","title":"Hepatic in vitro metabolism of peptides; Comparison of human liver S9, hepatocytes and Upcyte hepatocytes with cyclosporine A, leuprorelin, desmopressin and cetrorelix as model compounds.","authors":"Jyrkäs, Juha; Tolonen, Ari","year":2021,"journal":"Journal of pharmaceutical and biomedical analysis, 196, 113921","doi":"10.1016/j.jpba.2021.113921","pmid":"33548873","tags":["bioavailability","peptide-safety"],"studyType":"In Vitro Comparative Study","evidenceStrength":"Moderate","keyFinding":"Comparison of human liver S9, hepatocyte spheroids, and other in vitro systems revealed model-dependent differences in peptide metabolism prediction, informing best practices for peptide drug development.","whyItMatters":"Better liver metabolism prediction for peptides means more accurate dosing, fewer clinical failures, and faster drug development for the growing class of peptide therapeutics.","specificNumbers":"4 peptides (cyclosporine, leuprorelin, desmopressin, cetrorelix); S9 most metabolites for 2; CYP-dependent metabolism found; hydrolytic similar across systems","methodology":"In vitro metabolism study comparing multiple hepatic models for peptide degradation. Human liver S9 fractions and hepatocyte spheroids evaluated.","limitations":"In vitro models may not fully replicate in vivo liver metabolism. Limited number of peptide compounds tested. Inter-individual variability in human liver not fully captured."},{"rthcId":"RPEP-05477","title":"Cell-penetrating peptide-conjugated lipid/polymer hybrid nanovesicles for endoplasmic reticulum-targeting intracellular delivery.","authors":"Kang, Jeong Yi; Kim, Seulgi; Kim, Juhyeon; Kang, Nae-Gyu; Yang, Chul-Su; Min, Sun-Joon; Kim, Jin Woong","year":2021,"journal":"Journal of materials chemistry. B, 9(2), 464-470","doi":"10.1039/d0tb01940b","pmid":"33289751","tags":["cell-penetrating","peptide-delivery"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Penetratin-conjugated LPNVs showed efficient cellular uptake, specific ER-targeting, and remarkable lysosomal escape due to pH buffering by PEO-b-PCL-b-PEO, enabling intracellular ER-targeted delivery.","whyItMatters":"ER dysfunction drives many diseases but has been difficult to target therapeutically. A delivery system that specifically reaches the ER inside cells could enable a new class of subcellular precision medicines.","specificNumbers":"9% lysosomal co-localization for CPP-coated nanovesicles vs. higher rates for controls","methodology":"In vitro study. Lipid/polymer hybrid nanovesicles (PEO-b-PCL-b-PEO + DPPC) conjugated with Penetratin CPP. Cellular uptake, ER co-localization, lysosomal escape, and comparison with other CPP-conjugated LPNVs assessed.","limitations":"In vitro cell culture study. No disease model testing. ER-targeting specificity in vivo unknown. Drug loading and therapeutic efficacy not demonstrated. Nanoparticle manufacturing scalability not addressed."},{"rthcId":"RPEP-05478","title":"Toxin-Activating Stapled Peptides Discovered by Structural Analysis Were Identified as New Therapeutic Candidates That Trigger Antibacterial Activity against Mycobacterium tuberculosis in the Mycobacterium smegmatis Model.","authors":"Kang, Sung-Min; Moon, Heejo; Han, Sang-Woo; Kim, Byeong Wook; Kim, Do-Hee; Kim, Byeong Moon; Lee, Bong-Jin","year":2021,"journal":"Microorganisms, 9(3)","doi":"10.3390/microorganisms9030568","pmid":"33801872","tags":["antimicrobial-peptides","cyclic-peptides","infection","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Stapled peptide V26-SP-8 activates VapC26 toxin in M. tuberculosis through optimized α-helix stabilization. Enhanced activity and cell permeability from hydrocarbon stapling. Effective against MDR-TB and XDR-TB targets.","whyItMatters":"TB kills 1.5 million people yearly, and drug-resistant strains are spreading. A peptide that turns the bacterium's own toxin system against it represents a fundamentally new antibiotic mechanism that drug-resistant bacteria cannot easily evade.","specificNumbers":"V26-SP-8 showed highest activity among stapled peptide candidates tested","methodology":"Structure-based peptide design from VapBC toxin-antitoxin system crystal structure. Systematic hydrocarbon α-helix stapling optimization. In vitro validation of VapC26 activation and cell permeability.","limitations":"In vitro validation only. In vivo TB treatment efficacy not tested. Peptide delivery to TB bacteria inside human macrophages (where TB hides) not assessed. Manufacturing costs for stapled peptides."},{"rthcId":"RPEP-05479","title":"Dipeptidyl peptidase-4 inhibitors, glucagon-like peptide 1 receptor agonists and sodium-glucose co-transporter-2 inhibitors for people with cardiovascular disease: a network meta-analysis.","authors":"Kanie, Takayoshi; Mizuno, Atsushi; Takaoka, Yoshimitsu; Suzuki, Takahiro; Yoneoka, Daisuke; Nishikawa, Yuri; Tam, Wilson Wai San; Morze, Jakub; Rynkiewicz, Andrzej; Xin, Yiqiao; Wu, Olivia; Providencia, Rui; Kwong, Joey Sw","year":2021,"journal":"The Cochrane database of systematic reviews, 10(10), CD013650","doi":"10.1002/14651858.CD013650.pub2","pmid":"34693515","tags":["glp-1","diabetes","cardiovascular","clinical-trials"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"GLP-1RA: reduced CV death (OR 0.87), all-cause death (OR 0.88), stroke (OR 0.87) — all high-certainty. SGLT2i: reduced CV death (OR 0.82), all-cause death (OR 0.84), HF hospitalization (OR 0.65). DPP4i: no benefit on any CV outcome. DPP4i likely increase pancreatitis (OR 1.63). 129,465 participants, 20 studies.","whyItMatters":"This definitive comparison helps doctors choose the right diabetes drug for patients with heart disease. DPP-4 inhibitors clearly fall short, while GLP-1 and SGLT2 drugs save lives — with each class excelling at different cardiovascular endpoints.","specificNumbers":"GLP-1RA CV mortality OR 0.87; SGLT2i CV mortality OR 0.82; SGLT2i HF hospitalization OR 0.65; DPP4i pancreatitis OR 1.63","methodology":"Cochrane systematic review and network meta-analysis. 31 studies identified (287 records), 20 pooled (129,465 participants). 6 DPP4i, 7 GLP-1RA, 7 SGLT2i trials. Standard and network meta-analysis. GRADE certainty assessment. Risk of bias evaluation.","limitations":"No direct head-to-head comparisons between the three drug classes (network meta-analysis uses indirect comparisons). Most participants had established CVD — results may differ in primary prevention. Individual drug-level differences within classes not fully explored."},{"rthcId":"RPEP-05480","title":"Computational Design of Macrocyclic Binders of S100B(ββ): Novel Peptide Theranostics.","authors":"Kannan, Srinivasaraghavan; Aronica, Pietro G A; Nguyen, Thanh Binh; Li, Jianguo; Verma, Chandra S","year":2021,"journal":"Molecules (Basel, Switzerland), 26(3)","doi":"10.3390/molecules26030721","pmid":"33573254","tags":["cyclic-peptides","peptide-design","cancer"],"studyType":"computational","evidenceStrength":"preliminary","keyFinding":"Computationally designed stapled macrocyclic peptides predicted to bind S100B(ββ) with high affinity. Modified with imaging agents for theranostic applications. Designed to disrupt S100B-partner protein interactions driving cancer and neurodegeneration.","whyItMatters":"S100B is implicated in melanoma, glioblastoma, Alzheimer's, and inflammatory conditions but has been \"undruggable\" with small molecules. Stapled peptides that both diagnose and treat could transform S100B-driven disease management.","specificNumbers":"Multiple optimized stapled peptide analogs with predicted high-affinity S100B binding","methodology":"Computational study. Comparative structural analysis of S100B-peptide complexes. Molecular dynamics simulations. Stapled peptide design and in silico mutagenesis optimization. Imaging agent conjugation for theranostic functionality.","limitations":"Entirely computational — no experimental binding validation. Predicted affinities require in vitro confirmation. In vivo peptide delivery and imaging agent function not tested. Stapled peptide cell permeability assumed but not verified."},{"rthcId":"RPEP-05481","title":"Identification of a Putative β-Arrestin Superagonist of the Growth Hormone Secretagogue Receptor (GHSR).","authors":"Karaki, Fumika; Oki, Tomoya; Sakao, Yuma; Sato, Noriko; Hirayama, Shigeto; Miyano, Kanako; Uezono, Yasuhito; Fujii, Hideaki","year":2021,"journal":"ChemMedChem, 16(22), 3463-3476","doi":"10.1002/cmdc.202100322","pmid":"34278724","tags":["ipamorelin","receptor-signaling","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Discovered a putative β-arrestin-biased GHSR superagonist through dual screening (calcium antagonism + ERK1/2 phosphorylation). Activity not completely blocked by competitive antagonist, suggesting allosteric binding mechanism.","whyItMatters":"β-arrestin signaling through GHSR is linked to neuroprotective effects. A biased agonist that activates this pathway without the hunger-promoting Gαq signaling could provide neurological benefits without appetite side effects.","specificNumbers":"Superagonist ERK1/2 activity; activity not fully blocked by competitive antagonist","methodology":"In vitro pharmacology study. Two-step screening: calcium flux assay (Gαq antagonism) then ERK1/2 phosphorylation assay (β-arrestin activation). Competitive antagonist blockade experiments to assess binding site.","limitations":"In vitro screening study — functional in vivo effects unknown. \"Putative\" superagonist needs further characterization. Allosteric binding site not structurally defined. β-arrestin-biased GHSR signaling in vivo poorly understood."},{"rthcId":"RPEP-05482","title":"3D Printing of Antibacterial, Biocompatible, and Biomimetic Hybrid Aerogel-Based Scaffolds with Hierarchical Porosities via Integrating Antibacterial Peptide-Modified Silk Fibroin with Silica Nanostructure.","authors":"Karamat-Ullah, Nighat; Demidov, Yan; Schramm, Michael; Grumme, Daniela; Auer, Jaqueline; Bohr, Christoph; Brachvogel, Bent; Maleki, Hajar","year":2021,"journal":"ACS biomaterials science & engineering, 7(9), 4545-4556","doi":"10.1021/acsbiomaterials.1c00483","pmid":"34415718","tags":["antimicrobial-peptides","bone-joint","peptide-delivery"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"AMP-modified silk fibroin + silica nanostructure hybrid aerogel scaffolds achieved antibacterial activity, biocompatibility, and biomimetic hierarchical porosity through 3D printing for bone tissue engineering.","whyItMatters":"Bone implant infections affect up to 5% of orthopedic surgeries and can require implant removal. A scaffold that inherently fights bacteria while supporting bone growth could dramatically reduce these complications.","specificNumbers":"Potent activity against gram-positive and gram-negative bacteria; hierarchical porosity achieved via 3D printing + freeze-casting","methodology":"3D printing of hybrid aerogel scaffolds. Antimicrobial peptide conjugation to silk fibroin. Silica nanostructure integration. Characterization of porosity, mechanical properties, antibacterial activity, and biocompatibility.","limitations":"In vitro characterization. No in vivo bone regeneration or infection prevention data. Long-term mechanical stability and AMP activity durability not assessed. Manufacturing reproducibility for clinical-grade scaffolds unknown."},{"rthcId":"RPEP-05483","title":"Synthesis of six-membered carbocyclic ring α,α-disubstituted amino acids and arginine-rich peptides to investigate the effect of ring size on the properties of the peptide.","authors":"Kato, Takuma; Kita, Yuki; Iwanari, Kazuki; Asano, Akiko; Oba, Makoto; Tanaka, Masakazu; Doi, Mitsunobu","year":2021,"journal":"Bioorganic & medicinal chemistry, 38, 116111","doi":"10.1016/j.bmc.2021.116111","pmid":"33838611","tags":["cell-penetrating","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Six-membered carbocyclic α,α-disubstituted amino acids were synthesized and incorporated into arginine-rich CPPs. Ring size affected peptide helicity and cell-penetrating properties, providing design insights for CPP optimization.","whyItMatters":"Better CPPs mean better drug delivery. Understanding how subtle structural changes (like ring size) affect cell penetration guides rational design of next-generation delivery peptides.","specificNumbers":"dAA peptides outperformed Arg9 in stability and uptake; 5- vs 6-membered ring showed no significant difference","methodology":"Organic synthesis of six-membered carbocyclic dAAs. Peptide synthesis incorporating the unnatural amino acids. Structural characterization. Cell penetration assays comparing five- and six-membered ring variants.","limitations":"Synthetic chemistry and in vitro study. Limited number of peptide sequences tested. In vivo delivery performance not assessed."},{"rthcId":"RPEP-05484","title":"Oxytocin-induced increase in N,N-dimethylglycine and time course of changes in oxytocin efficacy for autism social core symptoms.","authors":"Kato, Yasuhiko; Kuwabara, Hitoshi; Okada, Takashi; Munesue, Toshio; Benner, Seico; Kuroda, Miho; Kojima, Masaki; Yassin, Walid; Eriguchi, Yosuke; Kameno, Yosuke; Murayama, Chihiro; Nishimura, Tomoko; Tsuchiya, Kenji; Kasai, Kiyoto; Ozaki, Norio; Kosaka, Hirotaka; Yamasue, Hidenori","year":2021,"journal":"Molecular autism, 12(1), 15","doi":"10.1186/s13229-021-00423-z","pmid":"33622389","tags":["oxytocin","anxiety-mood","neuropeptides","clinical-trials"],"studyType":"rct","evidenceStrength":"moderate","keyFinding":"Oxytocin increased N,N-dimethylglycine (FDR p=0.043, d=0.74; N=83). In high-responder subgroup: FDR p=0.004, d=1.13, N=60. DMG increase correlated with clinical improvement at 2 weeks (r=-0.485, p=0.006) and deterioration at 2-4 weeks (r=0.415, p=0.032).","whyItMatters":"This explains the biggest puzzle in oxytocin-ASD research: why benefits don't last. The NMDA receptor/plasticity mechanism suggests that intermittent dosing or combination approaches could maintain oxytocin's benefits without tolerance.","specificNumbers":"N=106; DMG d=0.74 (p=0.043); subgroup d=1.13 (p=0.004); improvement r=-0.485; deterioration r=0.415; 48 IU/day; 6 weeks","methodology":"Multi-center, parallel-group, double-blind, placebo-controlled RCT. 106 adult males with ASD. Intranasal oxytocin 48 IU/day or placebo for 6 weeks. Plasma metabolomics (35 metabolites). Facial expression analysis for clinical outcomes. UMIN000015264.","limitations":"Blood metabolites may not reflect brain changes. Only adult males studied. Facial expression analysis as clinical outcome is novel but not a standard ASD measure. Subgroup analyses reduce statistical power. Correlation does not prove causation."},{"rthcId":"RPEP-05485","title":"In-Silico Tool for Predicting, Scanning, and Designing Defensins.","authors":"Kaur, Dilraj; Patiyal, Sumeet; Arora, Chakit; Singh, Ritesh; Lodhi, Gaurav; Raghava, Gajendra P S","year":2021,"journal":"Frontiers in immunology, 12, 780610","doi":"10.3389/fimmu.2021.780610","pmid":"34880873","tags":["antimicrobial-peptides","peptide-design","immune-function"],"studyType":"computational","evidenceStrength":"preliminary","keyFinding":"Developed a systematic computational tool for predicting defensins from peptide sequences, scanning genomes for novel defensins, and designing new defensin antimicrobial peptides with high accuracy.","whyItMatters":"The antibiotic resistance crisis demands new antimicrobials. This tool dramatically accelerates defensin discovery by replacing slow, expensive laboratory screening with rapid computational prediction.","specificNumbers":"AUC 0.98 (defensin vs AMP); AUC 0.99 (defensin vs non-defensin); MCC 0.88 and 0.96 respectively","methodology":"Computational study. Machine learning models trained on known defensin sequences. Three functionalities: prediction (is this a defensin?), scanning (find defensins in genomes), and design (create new defensins). Performance validated against experimental data.","limitations":"Computational predictions require experimental validation. Training data may bias toward known defensin families. Predicted peptides need synthesis and antimicrobial testing. Designed defensins may face bioavailability challenges."},{"rthcId":"RPEP-05486","title":"Designing aromatic N-cadherin mimetic short-peptide-based bioactive scaffolds for controlling cellular behaviour.","authors":"Kaur, Harsimran; Roy, Sangita","year":2021,"journal":"Journal of materials chemistry. B, 9(29), 5898-5913","doi":"10.1039/d1tb00598g","pmid":"34263278","tags":["peptide-design","neuroprotection","wound-healing"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Aromatic N-cadherin mimetic pentapeptides (Fmoc-HAVDI and Nap-HAVDI) self-assembled into nanofibrous hydrogels that matched the mechanical properties of neural ECM and supported adhesion and proliferation of both neural and non-neural cell lines.","whyItMatters":"Simple peptide-based scaffolds that support nerve cell growth could be useful for nerve repair and tissue engineering. The minimalist design makes them easier and cheaper to produce.","specificNumbers":"HAVDI pentapeptide is the shortest N-cadherin mimic; hydrogel stiffness matched neural ECM","methodology":"Lab study. Designed and synthesized modified pentapeptides from the N-cadherin HAVDI sequence. Characterized self-assembly, nanofiber structure, and mechanical properties. Tested cell adhesion, proliferation, and protein expression in neural and non-neural cell lines.","limitations":"Cell culture study only. No animal testing of the scaffolds. Long-term stability and behavior in the body are unknown."},{"rthcId":"RPEP-05487","title":"Ninjinyoeito improves anxiety behavior in neuropeptide Y deficient zebrafish.","authors":"Kawabe, Momoko; Hayashi, Akito; Komatsu, Masaharu; Inui, Akio; Shiozaki, Kazuhiro","year":2021,"journal":"Neuropeptides, 87, 102136","doi":"10.1016/j.npep.2021.102136","pmid":"33721592","tags":["neuropeptides","anxiety-mood"],"studyType":"animal","evidenceStrength":"preliminary","keyFinding":"NYT suppressed anxiety behaviors in NPY-KO zebrafish after 4-day dietary supplementation, with reduced tyrosine hydroxylase and ERK phosphorylation in brain. 9/12 component herbs reduced freezing. Schisandra fruit and its lignan schizandrin were the most potent anxiolytic components.","whyItMatters":"NPY deficiency contributes to anxiety disorders in humans. Identifying natural compounds that compensate for NPY-related anxiety could provide new treatment options, especially for patients who don't respond to conventional anxiolytics.","specificNumbers":"3% NYT diet; 4-day treatment; 9/12 herbs reduced freezing; schizandrin identified as active lignan","methodology":"Animal study. NPY-knockout zebrafish fed 3% NYT-supplemented or control diet for 4 days. Cold stress-induced anxiety behavioral tests. Brain tyrosine hydroxylase and ERK phosphorylation measured. Individual herbal components and Schisandra lignans tested for anxiolytic activity.","limitations":"Zebrafish model — anxiety behavior may not fully translate to human psychiatric conditions. Short treatment period (4 days). NPY complete knockout is more extreme than human NPY variation. Schizandrin mechanism of action beyond NPY system not fully elucidated."},{"rthcId":"RPEP-05488","title":"Evidence that increased cholecystokinin (CCK) in the periaqueductal gray (PAG) facilitates changes in Resident-Intruder social interactions triggered by peripheral nerve injury.","authors":"Keay, Kevin A; Argueta, Manuel A; Zafir, Daniel N; Wyllie, Peter M; Michael, Gregory J; Boorman, Damien C","year":2021,"journal":"Journal of neurochemistry, 158(5), 1151-1171","doi":"10.1111/jnc.15476","pmid":"34287873","tags":["neuropeptides","pain"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"Chronic nerve injury increased CCK mRNA in ventrolateral PAG and dorsal raphe neurons and CCK-8 peptide in PAG terminal boutons. Microinjection of CCK-8 into rostral lateral/ventrolateral PAG of uninjured rats reproduced CCI-induced social behavior disruptions.","whyItMatters":"Social withdrawal in chronic pain is a major quality-of-life issue that current pain treatments don't address. Identifying CCK in the PAG as the molecular cause suggests that CCK receptor blockers could restore social functioning in chronic pain patients.","specificNumbers":"Increased CCK mRNA in vlPAG and dorsal raphe; CCK-8 peptide elevated in lateral/ventrolateral PAG terminals; microinjection in rostral PAG reproduced social deficits","methodology":"Animal study. Sciatic nerve chronic constriction injury (CCI) in rats. RT-PCR for CCK mRNA. Immunohistochemistry for CCK-8 peptide localization. Resident-Intruder social behavior testing. CCK-8 microinjection into PAG of uninjured rats with behavioral observation.","limitations":"Rat model — human social behavior is more complex. Direct PAG injection is not clinically practical. Only a subset of rats showed persistent social changes. CCK receptor subtype specificity not determined."},{"rthcId":"RPEP-05489","title":"Extraction optimization for combined metabolomics, peptidomics, and proteomics analysis of gut microbiota samples.","authors":"Keller, Caitlin; Wei, Pingli; Wancewicz, Benjamin; Cross, Tzu-Wen L; Rey, Federico E; Li, Lingjun","year":2021,"journal":"Journal of mass spectrometry : JMS, 56(4), e4625","doi":"10.1002/jms.4625","pmid":"32885503","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05490","title":"Induced Disassembly of a Virus-like Particle under Physiological Conditions for Venom Peptide Delivery.","authors":"Kelly, M Patrick; Napolitano, Tanya; Anand, Prachi; Ho, Justin S K; Jabeen, Shakeela; Kuppan, Jessica; Manir, Sujoy; Holford, Mandë","year":2021,"journal":"Bioconjugate chemistry, 32(1), 111-120","doi":"10.1021/acs.bioconjchem.0c00494","pmid":"33306347","tags":["venom-peptides","peptide-delivery"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Ring-opening metathesis polymerization (ROMP) mechanism enables controllable P22 VLP disassembly under physiological conditions (neutral pH, moderate temperature). Norbornene-conjugated VLPs disassemble upon AquaMet catalyst treatment, releasing GFP reporter cargo.","whyItMatters":"Therapeutic venom peptides (like the pain drug ziconotide) are potent but fragile. A nanoparticle delivery system with on-demand release could protect peptide drugs during circulation and release them specifically at disease sites.","specificNumbers":"Disassembly confirmed by electrophoresis, TEM, and DLS at neutral pH and moderate temperature","methodology":"Chemical biology study. Norbornene conjugated to P22 VLP surface lysines. ROMP induced by water-soluble AquaMet ruthenium catalyst. Disassembly confirmed by native agarose electrophoresis, TEM, and dynamic light scattering. Adaptable to other VLP prototypes.","limitations":"Proof-of-concept with GFP reporter, not actual venom peptide cargo. AquaMet catalyst administration in vivo may have safety concerns. Release kinetics and spatial control not optimized. In vivo delivery not tested."},{"rthcId":"RPEP-05491","title":"The Effects of Oxytocin on Appetite Regulation, Food Intake and Metabolism in Humans.","authors":"Kerem, Liya; Lawson, Elizabeth A","year":2021,"journal":"International journal of molecular sciences, 22(14)","doi":"10.3390/ijms22147737","pmid":"34299356","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05492","title":"Beyond GnRH, LH and FSH: The role of kisspeptin on hypothalalmic-pituitary gonadal (HPG) axis pathology and diagnostic consideration.","authors":"Khan, Sikandar Hayat; Chaudhry, Nayyer","year":2021,"journal":"JPMA. The Journal of the Pakistan Medical Association, 71(7), 1862-1869","doi":"10.47391/JPMA.133","pmid":"34410262","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05493","title":"The effects of collagen peptide supplementation on body composition, collagen synthesis, and recovery from joint injury and exercise: a systematic review.","authors":"Khatri, Mishti; Naughton, Robert J; Clifford, Tom; Harper, Liam D; Corr, Liam","year":2021,"journal":"Amino acids, 53(10), 1493-1506","doi":"10.1007/s00726-021-03072-x","pmid":"34491424","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05494","title":"Peptide KED: Molecular-Genetic Aspects of Neurogenesis Regulation in Alzheimer's Disease.","authors":"Khavinson, V Kh; Lin'kova, N S; Umnov, R S","year":2021,"journal":"Bulletin of experimental biology and medicine, 171(2), 190-193","doi":"10.1007/s10517-021-05192-6","pmid":"34173097","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05495","title":"Peptide Regulation of Gene Expression: A Systematic Review.","authors":"Khavinson, Vladimir Khatskelevich; Popovich, Irina Grigor'evna; Linkova, Natalia Sergeevna; Mironova, Ekaterina Sergeevna; Ilina, Anastasiia Romanovna","year":2021,"journal":"Molecules (Basel, Switzerland), 26(22)","doi":"10.3390/molecules26227053","pmid":"34834147","tags":[],"studyType":"systematic-review","evidenceStrength":"moderate","keyFinding":"Short peptides consisting of just 2–7 amino acid residues can penetrate cell nuclei and nucleoli, where they interact directly with nucleosomes, histone proteins, and both single- and double-stranded DNA. These DNA–peptide interactions include sequence recognition in gene promoters, which is critical for replication, transcription, and DNA repair.\n\nThe review also found that short peptides can regulate DNA methylation status — an epigenetic mechanism that activates or represses genes in normal conditions, pathological states, and during aging. The authors propose that short peptides were likely among the earliest signaling molecules in evolution, directing template-based synthesis reactions.","whyItMatters":"Understanding how small peptides directly regulate gene expression opens the door to a new class of therapeutics. If peptides as short as 2–7 amino acids can switch genes on or off through epigenetic mechanisms, they could offer targeted treatments for aging, immune dysfunction, neurodegeneration, and infections — with potentially fewer side effects than larger drug molecules.","specificNumbers":"2–7 amino acid residues · penetrate nuclei and nucleoli · interact with nucleosome, histones, and DNA · regulate DNA methylation","methodology":"This was a systematic review that analyzed published research across multiple organisms — plants, microorganisms, insects, birds, rodents, primates, and humans — to map how short peptides interact with DNA and regulate gene expression at the molecular level.","limitations":"As a review paper, this study synthesizes existing research rather than generating new experimental data. The breadth of organisms covered (from plants to humans) means not all findings translate directly to human medicine. Additionally, many of the mechanisms described are based on in vitro or animal studies, with limited clinical validation in humans."},{"rthcId":"RPEP-05496","title":"Hybrid Cyclic-Linear Cell-Penetrating Peptides Containing Alternative Positively Charged and Hydrophobic Residues as Molecular Transporters.","authors":"Khayyatnejad Shoushtari, Sorour; Zoghebi, Khalid; Sajid, Muhammad Imran; Tiwari, Rakesh Kumar; Parang, Keykavous","year":2021,"journal":"Molecular pharmaceutics, 18(10), 3909-3919","doi":"10.1021/acs.molpharmaceut.1c00594","pmid":"34491768","tags":["cell-penetrating","cyclic-peptides","cancer","peptide-delivery"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Hybrid cyclic-linear CPPs with alternative positively charged and hydrophobic amino acids showed enhanced cellular uptake and delivery of cell-impermeable, negatively charged molecules.","whyItMatters":"Better CPP architectures mean more efficient drug delivery into cells. The hybrid approach addresses limitations of both pure linear (unstable) and pure cyclic (rigid) CPPs.","specificNumbers":"18-fold uptake increase (CCRF-CEM); 11-fold (SK-OV-3); no toxicity at 10 μM; partial endocytosis independence","methodology":"Synthesis and biological evaluation of a novel series of hybrid cyclic-linear peptides. Cellular uptake measured with various cargo molecules.","limitations":"In vitro uptake study. Cargo diversity limited. In vivo delivery and therapeutic applications not tested. Manufacturing complexity of hybrid peptides."},{"rthcId":"RPEP-05497","title":"Monocyclic Peptides: Types, Synthesis and Applications.","authors":"Khazaei-Poul, Yalda; Farhadi, Shohreh; Ghani, Sepideh; Ahmadizad, Safar Ali; Ranjbari, Javad","year":2021,"journal":"Current pharmaceutical biotechnology, 22(1), 123-135","doi":"10.2174/1573412916666200120155104","pmid":"31987019","tags":["cyclic-peptides","peptide-design"],"studyType":"review","evidenceStrength":"n/a-review","keyFinding":"Comprehensive review covering monocyclic peptide classification, synthesis methods (chemical and enzymatic), and applications in bioactive molecule design, targeted therapeutics, diagnostics, and vaccine development.","whyItMatters":"Cyclic peptides are one of the fastest-growing drug classes, bridging the gap between small molecules and biologics. Understanding their types and synthesis enables rational design for diverse therapeutic applications.","specificNumbers":"Covers antimicrobial, anticancer, delivery, diagnostic, and agricultural cyclic peptide applications","methodology":"Narrative review of monocyclic peptide chemistry, synthesis, and biomedical applications.","limitations":"Broad review covering many topics without deep analysis of any single application. Some synthesis methods are technically challenging at scale. Clinical evidence varies widely between applications."},{"rthcId":"RPEP-05498","title":"The Cysteine-Containing Cell-Penetrating Peptide AP Enables Efficient Macromolecule Delivery to T Cells and Controls Autoimmune Encephalomyelitis.","authors":"Kim, Won-Ju; Kim, Gil-Ran; Cho, Hyun-Jung; Choi, Je-Min","year":2021,"journal":"Pharmaceutics, 13(8)","doi":"10.3390/pharmaceutics13081134","pmid":"34452095","tags":["cell-penetrating","immune-function","inflammation","neuroprotection"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"AP CPP (9 amino acids with one cysteine) delivered EGFP to human T cells and biodistributed to spleen, liver, intestines, and brain after systemic administration. AP-ctCTLA-4 reduced Th17 differentiation in vitro and ameliorated EAE with decreased IL-17A+GM-CSF+ CD4 T cells in vivo.","whyItMatters":"T cell-targeted drug delivery is a holy grail of immunotherapy. A CPP that delivers regulatory peptides into T cells AND crosses the blood-brain barrier could treat MS and other autoimmune conditions more effectively than current drugs.","specificNumbers":"9-AA optimal CPP sequence; crossed BBB; reduced IL-17A+ GM-CSF+ CD4 T cells in EAE","methodology":"In vitro and in vivo study. AP peptide sequence optimization for T cell delivery. Biodistribution after systemic administration. AP-ctCTLA-4 conjugate tested for Th17 suppression in vitro and EAE amelioration in vivo. Flow cytometry for T cell phenotyping.","limitations":"Mouse EAE model — human MS is more complex. Systemic AP delivery may have off-target effects in other tissues. CTLA-4 pathway modulation could cause immunosuppression. Long-term safety not assessed. Peptide stability in circulation unknown."},{"rthcId":"RPEP-05499","title":"The role of central corticotrophin-releasing factor receptor signalling in plasma glucose maintenance through ghrelin secretion in calorie-restricted mice.","authors":"Kimura, Risa; Kondo, Daisuke; Takemi, Shota; Fujishiro, Miyuki; Tsukahara, Shinji; Sakai, Takafumi; Sakata, Ichiro","year":2021,"journal":"Journal of neuroendocrinology, 33(3), e12961","doi":"10.1111/jne.12961","pmid":"33675127","tags":["neuropeptides","hormone-optimization","diabetes"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"Central CRF-R signaling → sympathetic activation → ghrelin secretion → plasma glucose maintenance during 60% calorie restriction. Blocking CRF-R, beta-1 receptors, or ghrelin receptors all reduced glucose. Ghrelin co-administration rescued glucose in each case.","whyItMatters":"Understanding how the brain coordinates metabolic survival responses through peptide hormone cascades is fundamental to treating hypoglycemia, eating disorders, and metabolic crises. It also reveals why severe dieting can be metabolically dangerous.","specificNumbers":"60% calorie restriction; CRF receptor activation raised ghrelin; atenolol blocked ghrelin elevation; ghrelin rescued glucose drops from CRF or beta-1 blockade","methodology":"Animal study. Intracerebroventricular injections of urocortin-1, urocortin-2, and CRF-R antagonist in mice. 60% calorie restriction model. Ghrelin receptor antagonist (d-Lys3-GHRP-6) and atenolol treatment. Plasma ghrelin and glucose measurements. Rescue experiments with ghrelin co-administration.","limitations":"Mouse model with extreme calorie restriction (60%). CRF-R and ghrelin pathways may function differently under more moderate dietary restriction. ICV injection is not clinically translatable. Chronic effects not assessed."},{"rthcId":"RPEP-05500","title":"In Vivo Molecular Imaging of the Efficacy of Aminopeptidase N (APN/CD13) Receptor Inhibitor Treatment on Experimental Tumors Using 68Ga-NODAGA-c(NGR) Peptide.","authors":"Kis, Adrienn; Dénes, Noémi; Szabó, Judit P; Arató, Viktória; Beke, Lívia; Matolay, Orsolya; Enyedi, Kata Nóra; Méhes, Gábor; Mező, Gábor; Bai, Péter; Kertész, István; Trencsényi, György","year":2021,"journal":"BioMed research international, 2021, 6642973","doi":"10.1155/2021/6642973","pmid":"33778075","tags":["cancer","peptide-design"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"Bestatin treatment reduced tumor growth and 68Ga-NODAGA-c(NGR) PET uptake in HT1080 and B16-F10 tumors. The NGR peptide radiotracer specifically detected APN/CD13 expression changes, enabling in vivo monitoring of antiangiogenic treatment efficacy.","whyItMatters":"Currently, treatment response is often assessed weeks later by measuring tumor size. A peptide-based PET scan that detects molecular changes in real-time could enable doctors to switch ineffective treatments earlier, improving patient outcomes.","specificNumbers":"Bestatin 15 mg/kg 7d; actinonin 5 mg/kg 7d; 5.5 MBq 68Ga-NODAGA-c(NGR); significantly lower uptake after bestatin (p≤0.05 HT1080, p≤0.01 B16-F10)","methodology":"In vivo study. HT1080 and B16-F10 tumor-bearing mice treated with bestatin (15 mg/kg) or actinonin (5 mg/kg) IP × 7 days. PET scans on days 5 and 10 using 5.5 MBq 68Ga-NODAGA-c(NGR). Ex vivo biodistribution. Western blot for APN/CD13.","limitations":"Mouse subcutaneous tumor models. Actinonin showed inconsistent results between tumor types. Clinical translation of 68Ga-NGR PET needs human validation. APN/CD13 expression varies between human cancers."},{"rthcId":"RPEP-05501","title":"Intranasal oxytocin administration ameliorates social behavioral deficits in a POGZWT/Q1038R mouse model of autism spectrum disorder.","authors":"Kitagawa, Kohei; Matsumura, Kensuke; Baba, Masayuki; Kondo, Momoka; Takemoto, Tomoya; Nagayasu, Kazuki; Ago, Yukio; Seiriki, Kaoru; Hayata-Takano, Atsuko; Kasai, Atsushi; Takuma, Kazuhiro; Hashimoto, Ryota; Hashimoto, Hitoshi; Nakazawa, Takanobu","year":2021,"journal":"Molecular brain, 14(1), 56","doi":"10.1186/s13041-021-00769-8","pmid":"33726803","tags":["oxytocin","neuropeptides","anxiety-mood","nasal-peptides"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"POGZWT/Q1038R mice showed social deficits and reduced OXTR expression. POGZ binds to the OXTR promoter region, regulating its transcription. OXT neuron numbers in PVN were unchanged. Intranasal oxytocin effectively restored social behavior in POGZ mutant mice.","whyItMatters":"This is one of the clearest demonstrations of how a specific autism gene disrupts the oxytocin system. It provides both a mechanistic explanation and a therapeutic rationale: POGZ mutation patients specifically might benefit from intranasal oxytocin because their deficit is in oxytocin reception, not production.","specificNumbers":"Intranasal OXT restored social behavior; OXTR expression reduced; POGZ binds OXTR promoter; no change in PVN OXT neuron number","methodology":"Animal study. POGZWT/Q1038R knock-in mice with patient-derived ASD mutation. Social behavior testing. OXTR gene expression analysis. OXT neuron counting in paraventricular nucleus. Chromatin immunoprecipitation (ChIP) for POGZ binding to OXTR promoter. Intranasal oxytocin rescue experiments.","limitations":"Single POGZ mutation tested. Mouse social behavior may not capture all human ASD social deficits. OXTR expression measured globally, not in specific brain circuits. Intranasal oxytocin rescue was acute, not chronic. Translation to human POGZ patients needs confirmation."},{"rthcId":"RPEP-05502","title":"Complementary leucine zippering system for effective intracellular delivery of proteins by cell-penetrating peptides.","authors":"Kitamatsu, Mizuki; Yuasa, Hiroki; Ohtsuki, Takashi; Michiue, Hiroyuki","year":2021,"journal":"Bioorganic & medicinal chemistry, 33, 116036","doi":"10.1016/j.bmc.2021.116036","pmid":"33497939","tags":["cell-penetrating","peptide-delivery","cancer"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"The heterodimeric leucine zipper system (LzK/LzE) formed a 1:1 hybrid in solution, confirmed by fluorescence spectroscopy, effectively conjugating cargo proteins to cell-penetrating peptides without covalent modification.\n\nWhen used to deliver p53 (p53-LzK/LzE-CPP), the hybrid localized to cell nuclei and inhibited cell-specific proliferation across multiple cell lines. Critically, the leucine zipper delivery system outperformed the directly fused p53-CPP conjugate in proliferation inhibition, suggesting that the non-covalent, modular attachment preserves protein cargo activity better than direct fusion.","whyItMatters":"Most protein-based drugs can't cross cell membranes, severely limiting their therapeutic use. This leucine zipper system offers a modular, plug-and-play approach to intracellular protein delivery — any protein can be attached to any CPP without altering either component. The fact that it outperformed direct fusion means it better preserves the therapeutic protein's activity, which has been a persistent challenge in the field.","specificNumbers":"1:1 zipper hybrid; p53 nuclear localization; zipper system outperformed direct p53-CPP fusion in proliferation inhibition","methodology":"Researchers prepared two components: an EGFP or p53 protein fused to an acidic leucine zipper (LzK), and a basic leucine zipper (LzE) conjugated to a cell-penetrating peptide. Hybrid formation was confirmed by fluorescence spectroscopy and titration. Cellular delivery was assessed by fluorescence microscopy for EGFP and by cell proliferation assays for p53 across multiple cell lines. Results were compared against directly fused p53-CPP conjugates.","limitations":"This is entirely an in vitro cell culture study with no animal testing. The leucine zipper adds molecular weight that could affect in vivo pharmacokinetics, stability, and biodistribution. Serum stability of the zipper hybrid was not assessed. Whether the non-covalent zipper connection remains stable in blood circulation is unknown. Only p53 and EGFP were tested as cargo proteins."},{"rthcId":"RPEP-05503","title":"Chemistry of Peptide-Oligonucleotide Conjugates: A Review.","authors":"Klabenkova, Kristina; Fokina, Alesya; Stetsenko, Dmitry","year":2021,"journal":"Molecules (Basel, Switzerland), 26(17)","doi":"10.3390/molecules26175420","pmid":"34500849","tags":["cell-penetrating","peptide-design","peptide-delivery"],"studyType":"review","evidenceStrength":"n/a-review","keyFinding":"Peptide-oligonucleotide conjugates can be synthesized via stepwise solid-phase approaches or post-synthetic conjugation (especially click chemistry), each with distinct advantages for improving oligonucleotide cellular uptake and delivery.","whyItMatters":"Gene silencing therapies need better delivery. Understanding the chemistry of attaching delivery peptides to these drugs is essential for advancing the next generation of genetic medicines.","specificNumbers":"Covers stepwise solid-phase synthesis and multiple click chemistry conjugation strategies","methodology":"Literature review covering CPP structural types, intracellular transport mechanisms, non-covalent vs. covalent strategies, stepwise solid-phase synthesis, and post-synthetic conjugation including click chemistries.","limitations":"Review article. No new experimental data. The field evolves rapidly and some methods may already be superseded."},{"rthcId":"RPEP-05504","title":"Lessons from Wolfram Syndrome: Initiation of DDAVP Therapy Causes Renal Salt Wasting Due to Elevated ANP/BNP Levels, Rescued by Fludrocortisone Treatment.","authors":"Kleanthous, Kleanthis; Maratou, Eirini; Spyropoulou, Dora; Dermitzaki, Eleni; Papadimitriou, Anastasios; Zoupanos, George; Moutsatsou, Paraskevi; Mastorakos, George; Urano, Fumihiko; Papadimitriou, Dimitrios T","year":2021,"journal":"Indian journal of pediatrics, 88(6), 582-585","doi":"10.1007/s12098-020-03538-y","pmid":"33206325","tags":["natriuretic-peptides","neuropeptides"],"studyType":"case-report","evidenceStrength":"preliminary","keyFinding":"DDAVP initiation in untreated Wolfram DI caused ANP elevation ×50 and BNP ×2-4, blocking zona glomerulosa steroidogenesis, causing secondary mineralocorticoid deficiency and acute hyponatremia from RSW. Fludrocortisone 100-200 μg twice daily rescued electrolytes within 48 hours.","whyItMatters":"This identifies a potentially life-threatening complication when starting a common peptide drug (DDAVP) for diabetes insipidus. The natriuretic peptide-mediated mechanism explains why this happens and how to prevent or treat it.","specificNumbers":"ANP 50x elevated; BNP 2-4x elevated; fludrocortisone 100-200 μg BID; electrolytes normalized in 48h","methodology":"Clinical case report. Two sisters (19 and 7 years) with Wolfram syndrome and untreated DI. Initiated oral melt DDAVP. ANP and BNP levels measured. Electrolyte monitoring. Fludrocortisone treatment and response documented.","limitations":"Case report of two sisters (one family). Wolfram syndrome is extremely rare. The 50-fold ANP elevation may reflect the severity of untreated DI. Results may not generalize to milder volume expansion scenarios."},{"rthcId":"RPEP-05505","title":"Interruption of MDM2 signaling augments MDM2-targeted T cell-based antitumor immunotherapy through antigen-presenting machinery.","authors":"Kono, Michihisa; Kumai, Takumi; Hayashi, Ryusuke; Yamaki, Hidekiyo; Komatsuda, Hiroki; Wakisaka, Risa; Nagato, Toshihiro; Ohkuri, Takayuki; Kosaka, Akemi; Ohara, Kenzo; Kishibe, Kan; Takahara, Miki; Katada, Akihiro; Hayashi, Tatsuya; Celis, Esteban; Kobayashi, Hiroya; Harabuchi, Yasuaki","year":2021,"journal":"Cancer immunology, immunotherapy : CII, 70(12), 3421-3434","doi":"10.1007/s00262-021-02940-5","pmid":"33866408","tags":["cancer","immune-function"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"MDM232-46 peptide elicited antigen-specific CD4+ T cells that killed tumors via granzyme B. MDM2-reactive T cells found in head/neck cancer patients. Nutlin-3 augmented anti-tumor immunity by upregulating MDM2, HLA-I, and HLA-DR through CIITA.","whyItMatters":"Combining a peptide vaccine with a drug that makes tumors more visible to the immune system is a powerful synergistic strategy. MDM2-reactive T cells already exist in cancer patients, meaning the immune system is primed — it just needs a boost.","specificNumbers":"MDM232-46 peptide; CD4+ T cell activation; granzyme B-mediated killing; Nutlin-3 increased HLA-I, HLA-DR via CIITA","methodology":"Immunological study. MDM2 peptide epitope identification. CD4+ T cell response characterization including direct tumor killing via granzyme B. Head and neck cancer patient T cell analysis. Nutlin-3 effects on tumor antigen presentation (HLA-I, HLA-DR, CIITA).","limitations":"Preclinical immunological data. No clinical trial of MDM2 peptide vaccine. Patient T cell presence doesn't guarantee clinical response. Nutlin-3 toxicity and selectivity may limit clinical combination. Helper T cell-mediated killing is less common than cytotoxic T cell killing."},{"rthcId":"RPEP-05506","title":"Drug Addiction: Hyperkatifeia/Negative Reinforcement as a Framework for Medications Development.","authors":"Koob, George F","year":2021,"journal":"Pharmacological reviews, 73(1), 163-201","doi":"10.1124/pharmrev.120.000083","pmid":"33318153","tags":["neuropeptides","addiction","oxytocin","opioid-peptides"],"studyType":"review","evidenceStrength":"n/a-review","keyFinding":"Multiple neuropeptide systems (CRF, dynorphin, substance P, nociceptin, orexin, vasopressin, NPY, endocannabinoids, and others) are dysregulated in the extended amygdala/habenula during drug withdrawal, driving hyperkatifeia that motivates compulsive drug seeking across substances.","whyItMatters":"Most addiction treatments focus on the drug itself, not the emotional suffering that drives continued use. Targeting the neuropeptide systems behind negative withdrawal emotions could provide fundamentally better addiction treatments.","specificNumbers":"Covers CRF, dynorphin, norepinephrine, NPY, oxytocin, endocannabinoids, nociceptin systems in extended amygdala","methodology":"Comprehensive narrative review of neurochemical and neurocircuitry dysregulations underlying hyperkatifeia in addiction, focusing on the withdrawal/negative affect stage of the three-stage addiction model.","limitations":"Review article synthesizing extensive preclinical and clinical literature. Many neuropeptide-based treatments have failed in clinical trials despite strong preclinical evidence. The complexity of multiple interacting systems makes targeted treatment challenging."},{"rthcId":"RPEP-05507","title":"The Patient Experience of Premenopausal Women Treated with Bremelanotide for Hypoactive Sexual Desire Disorder: RECONNECT Exit Study Results.","authors":"Koochaki, Patricia; Revicki, Dennis; Wilson, Hilary; Pokrzywinski, Robin; Jordan, Robert; Lucas, Johna; Williams, Laura A; Sadiq, Amama; Krop, Julie","year":2021,"journal":"Journal of women's health (2002), 30(4), 587-595","doi":"10.1089/jwh.2020.8460","pmid":"33538638","tags":["pt-141","sexual-health","clinical-trials"],"studyType":"rct","evidenceStrength":"strong","keyFinding":"From 242 exit surveys and 80 telephone interviews, bremelanotide-treated women described increased sexual desire, physical arousal, and improved sexual activity quality — physiological responses not reported by placebo-treated women, who described non-physiological benefits only.","whyItMatters":"HSDD significantly impacts women's quality of life and relationships. Patient-reported outcomes confirming real physiological improvements — beyond placebo effects — validate bremelanotide as a genuine treatment, not just a psychological intervention.","specificNumbers":"242 exit surveys; 80 phone interviews; bremelanotide users reported desire, arousal, relationship quality improvements; placebo users reported communication benefits only","methodology":"Post-trial qualitative study from RECONNECT Phase 3 trials (NCT02333071, NCT02338960). 242 quantitative exit surveys (17 questions) and 80 qualitative telephone interviews (17 questions). Participants blinded to treatment assignment during assessment.","limitations":"Post-hoc qualitative analysis from a clinical trial population. Self-reported outcomes subject to recall and reporting bias. Limited to premenopausal women. Only 80 completed interviews. Cultural factors may influence reporting."},{"rthcId":"RPEP-05508","title":"A novel, injury-free rodent model of vulnerability for assessment of acute and preventive therapies reveals temporal contributions of CGRP-receptor activation in migraine-like pain.","authors":"Kopruszinski, Caroline M; Navratilova, Edita; Swiokla, Juliana; Dodick, David W; Chessell, Iain P; Porreca, Frank","year":2021,"journal":"Cephalalgia : an international journal of headache, 41(3), 305-317","doi":"10.1177/0333102420959794","pmid":"32985222","tags":["neuropeptides","pain"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"Novel injury-free two-hit hyperalgesic priming model produced CGRP-dependent migraine-like pain in mice. Sumatriptan (acute) and anti-CGRP antibody (preventive) both showed efficacy. CGRP receptor activation had distinct temporal contributions to pain phases. Sex differences observed.","whyItMatters":"Better migraine models lead to better drugs. This injury-free model more closely mimics human migraine vulnerability and revealed that CGRP plays different roles at different time points — information that could optimize the timing of anti-CGRP treatments.","specificNumbers":"3-day stress priming; 16-day latent sensitization; olcegepant preventive but not acute; sumatriptan acute but not preventive; nor-BNI prevented priming","methodology":"Animal study. C57BL/6 mice (male and female). Two-hit priming (CGRP exposure) + subthreshold TRPA1 challenge (umbellulone). Cutaneous allodynia and grimace measurements. Sumatriptan and anti-CGRP antibody treatment. Temporal analysis of CGRP contribution.","limitations":"Mouse model — migraine experience in humans is more complex. TRPA1 trigger may not represent all migraine triggers. Sex differences in mice may not match human sex differences. Model validation against clinical endpoints limited."},{"rthcId":"RPEP-05509","title":"Cell-Penetrating Peptides as a Potential Drug Delivery System for Effective Treatment of Diabetes.","authors":"Korivi, Mallikarjuna; Huang, Yue-Wern; Liu, Betty R","year":2021,"journal":"Current pharmaceutical design, 27(6), 816-825","doi":"10.2174/1381612826666201019102640","pmid":"33076803","tags":["cell-penetrating","diabetes","peptide-delivery","bioavailability"],"studyType":"review","evidenceStrength":"n/a-review","keyFinding":"CPPs enhance diabetes treatment by: (1) improving hypoglycemic drug effectiveness, (2) facilitating insulin delivery, (3) synergizing with immunosuppressants for islet transplantation, (4) prolonging drug pharmacokinetics, and (5) retarding diabetic nephropathy.","whyItMatters":"Diabetes affects 500+ million people. Better drug delivery means better glycemic control with fewer injections, fewer side effects, and potentially slowing the devastating complications that cause blindness, kidney failure, and amputation.","specificNumbers":"CPPs deliver proteins, DNA, RNA, liposomes, nanomaterials; applications in insulin delivery, islet transplant, nephropathy","methodology":"Narrative review of CPP applications in diabetes treatment, covering drug delivery mechanisms, therapeutic cargo types, and preclinical evidence for diabetes and its complications.","limitations":"Review of mostly preclinical evidence. CPP-drug formulations face manufacturing, stability, and regulatory challenges. In vivo evidence for diabetes-specific CPP delivery is still emerging. Cost-effectiveness versus current delivery methods unknown."},{"rthcId":"RPEP-05510","title":"A Review of the Efficacy and Cardiovascular Safety of Amylin Analogues.","authors":"Koshy, Rithika Mary; Fernandez, Cornelius James; Jacob, Koshy","year":2021,"journal":"Current drug safety, 16(2), 129-141","doi":"10.2174/1574886315999201105153852","pmid":"33153424","tags":["next-gen-agonists","diabetes","weight-loss","cardiovascular"],"studyType":"review","evidenceStrength":"n/a-review","keyFinding":"Pramlintide with insulin reduces HbA1c and weight with minimal/no hypoglycemia in T1DM and T2DM. Mechanisms: delayed gastric emptying, glucagon suppression, appetite reduction. Cardiovascular safety appears favorable. Shares mechanisms with GLP-1 RAs.","whyItMatters":"Pramlintide fills a treatment gap: patients on insulin who still have poor control and are gaining weight. Its unique mechanism (amylin replacement) addresses diabetes pathophysiology that insulin alone cannot fix.","specificNumbers":"Pramlintide improves HbA1c, promotes weight loss, delays gastric emptying, suppresses postprandial glucagon; favorable CV safety profile","methodology":"Narrative review of clinical trial evidence on pramlintide efficacy (HbA1c, weight, cognition), safety (hypoglycemia, cardiovascular), and comparison with GLP-1 receptor agonists when used as insulin adjunct therapy.","limitations":"Three daily injections limit adherence. Review does not include head-to-head pramlintide vs GLP-1RA trials. Weight loss is modest compared to newer GLP-1 drugs. Limited cognition data available. Pramlintide is underused in clinical practice."},{"rthcId":"RPEP-05511","title":"Application and validation of a coaxial liquid core waveguide fluorescence detector for the permeation analysis of desmopressin acetate.","authors":"Kottke, Dina; Burckhardt, Bjoern B; Breitkreutz, Jörg; Fischer, Björn","year":2021,"journal":"Talanta, 226, 122145","doi":"10.1016/j.talanta.2021.122145","pmid":"33676696","tags":["bioavailability","oral-peptides","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"A coaxial liquid-core waveguide fluorescence detector achieved a limit of detection of 4.7 ng/mL and lower limit of quantification of 9.5 ng/mL for desmopressin, enabling permeation analysis at clinically relevant dosages within one hour.","whyItMatters":"Better analytical tools help researchers develop oral and buccal peptide drugs. If peptides can be delivered through the mouth instead of by injection, patient compliance improves dramatically.","specificNumbers":"LOD 4.7 ng/mL; LLOQ 9.5 ng/mL; 1-hour permeation window","methodology":"Analytical chemistry study. Developed and validated an HPLC-coupled coaxial liquid-core waveguide fluorescence detector according to international guidelines. Used desmopressin acetate as the model peptide for permeation testing.","limitations":"Validated with one peptide (desmopressin) only. Performance with other peptides may vary. This is an analytical tool, not a drug study."},{"rthcId":"RPEP-05512","title":"Stability Test of PACAP in Eye Drops.","authors":"Kovacs, Anita K; Atlasz, Tamas; Werling, Dora; Szabo, Edina; Reglodi, Dora; Toth, Gabor K","year":2021,"journal":"Journal of molecular neuroscience : MN, 71(8), 1567-1574","doi":"10.1007/s12031-020-01532-9","pmid":"32323126","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05513","title":"The C-terminally shortened analogs of a hexapeptide derived from Lingzhi hydrolysate with enhanced tyrosinase-inhibitory activity.","authors":"Krobthong, Sucheewin; Yingchutrakul, Yodying; Samutrtai, Pawitrabhorn; Choowongkomon, Kiattawee","year":2021,"journal":"Archiv der Pharmazie, 354(11), e2100204","doi":"10.1002/ardp.202100204","pmid":"34313364","tags":["bioactive-food-peptides","skin-repair","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"The C-terminally shortened tripeptide VLT showed >23% improved tyrosinase inhibition compared to the parent hexapeptide VLTCGF, with binding via H-bonds (Asn260, Gly281) and electrostatic interaction (Glu256).","whyItMatters":"Shorter peptides are cheaper to make and often more stable. Finding that a three-amino-acid version works better than the original six-amino-acid peptide makes this a practical cosmetic ingredient candidate.","specificNumbers":"VLT tripeptide >23.27% improved activity vs VLTCGF; H-bonds to Asn260 and Gly281; electrostatic to Glu256","methodology":"Lab study. Isolated hexapeptide from protease-digested Lingzhi proteins by ultrafiltration and SPE. Identified by LC-MS/MS. Shortened analogs synthesized by solid-phase synthesis. Tyrosinase inhibition compared. Binding explained by molecular docking.","limitations":"In vitro tyrosinase inhibition only. No skin cell or human studies. Stability, skin penetration, and real-world efficacy not tested."},{"rthcId":"RPEP-05514","title":"Development of Cagrilintide, a Long-Acting Amylin Analogue.","authors":"Kruse, Thomas; Hansen, Jakob Lerche; Dahl, Kirsten; Schäffer, Lauge; Sensfuss, Ulrich; Poulsen, Christian; Schlein, Morten; Hansen, Ann Maria Kruse; Jeppesen, Claus Bekker; Dornonville de la Cour, Charlotta; Clausen, Trine Ryberg; Johansson, Eva; Fulle, Simone; Skyggebjerg, Rikke Bjerring; Raun, Kirsten","year":2021,"journal":"Journal of medicinal chemistry, 64(15), 11183-11194","doi":"10.1021/acs.jmedchem.1c00565","pmid":"34288673","tags":["next-gen-agonists","weight-loss","peptide-design"],"studyType":"preclinical","evidenceStrength":"moderate","keyFinding":"Researchers developed cagrilintide, a stable, lipidated long-acting amylin analogue that overcomes two major challenges of native amylin: its tendency to form amyloid fibrils and its very short half-life. Unlike pramlintide (the only approved amylin analogue), which requires three daily injections, cagrilintide's lipidation strategy enables once-weekly dosing.\n\nCagrilintide has induced significant weight loss in clinical trials both when used alone and when combined with the GLP-1 analogue semaglutide. The paper details the structure-activity relationship studies that led to selecting cagrilintide (compound 23) from a series of candidates for clinical development with obesity as the primary indication.","whyItMatters":"The obesity treatment landscape was transformed by GLP-1 drugs like semaglutide, and cagrilintide adds a complementary mechanism through the amylin pathway. Combined as CagriSema, these two peptides may represent the most effective non-surgical weight loss approach developed to date. This paper reveals the medicinal chemistry behind how cagrilintide was engineered — knowledge that informs future peptide drug design.","specificNumbers":"Compound 23 selected from series · Long-acting via lipidation · Once-weekly dosing potential · Significant weight loss alone + with semaglutide","methodology":"This is a medicinal chemistry study describing the iterative design, synthesis, and optimization of amylin analogues. Researchers evaluated structure-activity relationships across a series of peptide modifications, focusing on fibril resistance, lipidation strategies for extended half-life, receptor activity, and pharmacokinetic properties. Clinical trial data on weight loss efficacy are referenced from separate studies.","limitations":"This paper focuses on the drug design process rather than comprehensive clinical data. Full efficacy and safety results come from separate clinical trials. The structure-activity relationships described are specific to amylin analogues and may not generalize to other peptide classes."},{"rthcId":"RPEP-05515","title":"Sequence determinants in the cathelicidin LL-37 that promote inflammation via presentation of RNA to scavenger receptors.","authors":"Kulkarni, Nikhil N; O'Neill, Alan M; Dokoshi, Tatsuya; Luo, Elizabeth W C; Wong, Gerard C L; Gallo, Richard L","year":2021,"journal":"The Journal of biological chemistry, 297(1), 100828","doi":"10.1016/j.jbc.2021.100828","pmid":"34048712","tags":["ll-37","immune-function","inflammation"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Alanine scanning revealed: some substitutions increased antimicrobial activity, while hydrophobic face substitutions (F5A, I24A, L31A) inhibited scavenger receptor binding and inflammatory response without disrupting RNA organization. LL-37 functions as an \"innate immune vetter\" via SR-B1 binding.","whyItMatters":"Separating LL-37's antimicrobial and inflammatory functions is crucial for designing therapeutic peptides that kill bacteria without triggering harmful inflammation — relevant to conditions like psoriasis where LL-37-driven inflammation causes disease.","specificNumbers":"Hydrophobic face mutations abolished SR-B1 binding; maintained 3.5 nm inter-RNA spacing; some variants had enhanced antimicrobial activity","methodology":"Structure-function study. Alanine scanning of LL-34. Antimicrobial testing against S. aureus and GAS. Type 1 interferon induction with U1 RNA. SR-B1 binding on keratinocytes. Small-angle X-ray scattering (SAXS) of peptide-RNA complexes.","limitations":"Alanine scanning of LL-34 (slightly shorter than LL-37). In vitro studies with specific RNA (U1) and cell types. In vivo relevance of structural findings needs confirmation. Disease-context effects on LL-37 structure not addressed."},{"rthcId":"RPEP-05516","title":"Peptide-mediated leishmaniasis management strategy: Tachyplesin emerges as an effective anti-leishmanial peptide against Leishmania donovani.","authors":"Kumar, Vivek; Chugh, Archana","year":2021,"journal":"Biochimica et biophysica acta. Biomembranes, 1863(8), 183629","doi":"10.1016/j.bbamem.2021.183629","pmid":"33933430","tags":["antimicrobial-peptides","infection","venom-peptides","cell-penetrating"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Tachyplesin demonstrated effective anti-leishmanial activity against Leishmania donovani, the causative agent of visceral leishmaniasis, through a peptide-mediated parasite killing mechanism.","whyItMatters":"Visceral leishmaniasis kills tens of thousands annually and drug resistance is growing. AMPs like tachyplesin offer fundamentally different killing mechanisms that could overcome resistance to current antimonial and amphotericin B treatments.","specificNumbers":"Tachyplesin: membrane disruption mechanism; cysteine-dependent activity; dual antimicrobial + cargo delivery function","methodology":"In vitro and/or in vivo study testing tachyplesin antimicrobial peptide against Leishmania donovani. Anti-parasitic activity assessment.","limitations":"Preclinical data. Tachyplesin delivery to intracellular parasites (inside macrophages) is challenging. Toxicity to host cells needs assessment. Manufacturing and cost concerns for tropical disease applications."},{"rthcId":"RPEP-05517","title":"IRDye800CW labeled uPAR-targeting peptide for fluorescence-guided glioblastoma surgery: Preclinical studies in orthotopic xenografts.","authors":"Kurbegovic, Sorel; Juhl, Karina; Sørensen, Kasper Kildegaard; Leth, Julie; Willemoe, Gro Linno; Christensen, Anders; Adams, Yvonne; Jensen, Anja Ramstedt; von Buchwald, Christian; Skjøth-Rasmussen, Jane; Ploug, Michael; Jensen, Knud J; Kjaer, Andreas","year":2021,"journal":"Theranostics, 11(15), 7159-7174","doi":"10.7150/thno.49787","pmid":"34158842","tags":["cancer","peptide-design"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"IRDye800CW-labeled uPAR-targeting peptide provided specific fluorescence visualization of GBM tumor margins in orthotopic xenograft models, enabling fluorescence-guided surgical resection with clear tumor-to-background contrast.","whyItMatters":"The extent of GBM resection directly determines survival. A peptide that highlights tumor margins during surgery could mean the difference between leaving cancer behind and achieving complete removal.","specificNumbers":"TBR >4.5 at 1-12h; superior to 5-ALA; crossed BBB in 3D model; no acute toxicity","methodology":"Preclinical study. uPAR-targeting peptide conjugated with IRDye800CW near-infrared fluorescent dye. Orthotopic GBM xenograft models. Fluorescence-guided surgery. Tumor margin visualization assessed.","limitations":"Mouse xenograft model — human GBM is more heterogeneous. uPAR expression varies between patients. Near-infrared imaging requires specialized surgical equipment. No survival outcome data."},{"rthcId":"RPEP-05518","title":"Neuroprotective action of Cortexin, Cerebrolysin and Actovegin in acute or chronic brain ischemia in rats.","authors":"Kurkin, Denis V; Bakulin, Dmitry A; Morkovin, Evgeny I; Kalatanova, Anna V; Makarenko, Igor E; Dorotenko, Artem R; Kovalev, Nikolay S; Dubrovina, Marina A; Verkholyak, Dmitry V; Abrosimova, Elizaveta E; Smirnov, Alexey V; Shmidt, Maksim V; Tyurenkov, Ivan N","year":2021,"journal":"PloS one, 16(7), e0254493","doi":"10.1371/journal.pone.0254493","pmid":"34260655","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05519","title":"Roles of Neuropeptide S in Anesthesia, Analgesia, and Sleep.","authors":"Kushikata, Tetsuya; Hirota, Kazuyoshi; Saito, Junichi; Takekawa, Daiki","year":2021,"journal":"Pharmaceuticals (Basel, Switzerland), 14(5)","doi":"10.3390/ph14050483","pmid":"34069327","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05520","title":"The natriuretic peptide system in heart failure: Diagnostic and therapeutic implications.","authors":"Kuwahara, Koichiro","year":2021,"journal":"Pharmacology & therapeutics, 227, 107863","doi":"10.1016/j.pharmthera.2021.107863","pmid":"33894277","tags":["natriuretic-peptides","cardiovascular"],"studyType":"review","evidenceStrength":"n/a-review","keyFinding":"The review consolidates evidence that natriuretic peptides serve a dual role in heart failure — as diagnostic biomarkers and as cardioprotective agents. ANP and BNP directly oppose the effects of angiotensin II through diuretic/natriuretic actions (promoting water and sodium excretion), vasodilation (relaxing blood vessels), and inhibition of aldosterone secretion. CNP primarily regulates vascular tone and blood pressure.\n\nBNP and NT-proBNP (a cleavage product of proBNP processing) are elevated in heart failure patients and have become standard clinical biomarkers for detecting cardiac load. The review discusses how understanding the full biology of these peptides — from gene expression to receptor signaling — is informing development of natriuretic peptide-based therapeutics.","whyItMatters":"Heart failure affects tens of millions of people worldwide and remains a leading cause of hospitalization and death. Natriuretic peptide blood tests (BNP and NT-proBNP) have transformed how doctors diagnose and monitor heart failure, and understanding the underlying biology is critical for developing next-generation treatments. This review bridges the gap between basic peptide science and clinical cardiology.","specificNumbers":"Covers ANP, BNP, NT-proBNP, CNP as biomarkers and therapeutics; antagonistic to angiotensin II/aldosterone","methodology":"This is a comprehensive narrative review synthesizing basic science research, clinical studies, and translational findings on the natriuretic peptide family. It covers the physiological functions of ANP, BNP, and CNP, their roles in cardiovascular homeostasis, pathophysiological changes in heart failure, and clinical applications as biomarkers and therapeutic agents.","limitations":"This is a narrative review and does not include new experimental data. It reflects one author's synthesis and interpretation of the literature. As a 2021 publication, it may not capture the most recent clinical trial data on natriuretic peptide-based therapeutics."},{"rthcId":"RPEP-05521","title":"Self-Assembling Peptides: From Design to Biomedical Applications.","authors":"La Manna, Sara; Di Natale, Concetta; Onesto, Valentina; Marasco, Daniela","year":2021,"journal":"International journal of molecular sciences, 22(23)","doi":"10.3390/ijms222312662","pmid":"34884467","tags":["peptide-design","peptide-delivery"],"studyType":"review","evidenceStrength":"n/a-review","keyFinding":"Self-assembling peptides form a diverse range of micro- and nanostructures — including nanofibers, hydrogels, and nanotubes — that serve as platforms for tissue regeneration and drug delivery. By modifying amino acid composition, researchers can mimic biological functions, load both hydrophobic and hydrophilic drugs, and engineer stimuli-responsive release at targeted disease sites. The review highlights that biocompatibility and molecular recognition targeting are among their most significant advantages over conventional delivery systems.","whyItMatters":"Drug delivery remains one of the biggest challenges in medicine — getting the right amount of a drug to exactly where it's needed without side effects. Self-assembling peptides represent a promising platform that could improve how drugs are delivered, make tissue regeneration more effective, and ultimately lead to better patient outcomes.","specificNumbers":"Covers nanofibers, hydrogels, nanotubes for drug delivery and tissue engineering applications","methodology":"This is a literature review summarizing recent and significant studies on self-assembled peptide nanostructures, with emphasis on biomedical applications including drug delivery systems and tissue engineering scaffolds.","limitations":"As a review article, this does not present original experimental data. The field of self-assembling peptides evolves rapidly, so some methods discussed may have been superseded. The review primarily focuses on laboratory-stage research, and many of the described applications have not yet reached clinical trials in humans."},{"rthcId":"RPEP-05522","title":"Diabetes, insulin and new therapeutic strategies for Parkinson's disease: Focus on glucagon-like peptide-1 receptor agonists.","authors":"Labandeira, Carmen M; Fraga-Bau, Arturo; Arias Ron, David; Muñoz, Ana; Alonso-Losada, Gema; Koukoulis, Antonio; Romero-Lopez, Jesus; Rodriguez-Perez, Ana I","year":2021,"journal":"Frontiers in neuroendocrinology, 62, 100914","doi":"10.1016/j.yfrne.2021.100914","pmid":"33845041","tags":["glp-1","neuroprotection","diabetes"],"studyType":"review","evidenceStrength":"n/a-review","keyFinding":"Impaired insulin signaling contributes to Parkinson's disease pathogenesis through effects on neuronal survival, autophagy, synaptic plasticity, neurogenesis, and neuroinflammation. GLP-1 receptor agonists show neuroprotective effects in preclinical models and early clinical trials.","whyItMatters":"There are no disease-modifying treatments for Parkinson's. If GLP-1 drugs can slow neurodegeneration, they would be the first treatments to address the underlying disease rather than just symptoms.","specificNumbers":"Exenatide showed motor improvements in early Parkinson's trials; epidemiological data links diabetes to increased PD risk","methodology":"Narrative review of epidemiological studies, experimental animal research, and clinical trials examining the relationship between diabetes/insulin signaling and Parkinson's disease, and the neuroprotective potential of GLP-1 receptor agonists.","limitations":"Narrative review. Clinical trial data for GLP-1 drugs in Parkinson's is still limited to small, early-phase studies."},{"rthcId":"RPEP-05523","title":"Interleukin-4 Induces the Release of Opioid Peptides from M1 Macrophages in Pathological Pain.","authors":"Labuz, Dominika; Celik, Melih Ö; Seitz, Viola; Machelska, Halina","year":2021,"journal":"The Journal of neuroscience : the official journal of the Society for Neuroscience, 41(13), 2870-2882","doi":"10.1523/JNEUROSCI.3040-20.2021","pmid":"33593854","tags":["opioid-peptides","pain","immune-function","inflammation"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"IL-4 via IL-4Rα triggered dose-dependent release of Met-enkephalin, β-endorphin, and dynorphin A from M1 macrophages at injured nerves. Release was Ca2+-dependent via PKA, PI3K, and ryanodine receptors. Pain relief blocked by antibodies to each opioid peptide and all three opioid receptor antagonists.","whyItMatters":"This reveals a previously unknown mechanism where the immune system naturally produces opioid pain relief at injury sites. Targeting this IL-4-opioid pathway peripherally could provide effective pain control without the devastating side effects of systemic opioids.","specificNumbers":"3 opioid peptides (Met-ENK, β-endorphin, dynorphin A); 3 opioid receptor types (δ, μ, κ); PKA/PI3K/ryanodine/Ca2+ signaling; M1 macrophages as source","methodology":"Animal study. Chronic constriction nerve injury (CCI) in male mice. IL-4 injection at injured nerves. Mechanical hypersensitivity testing. Receptor blockade with antibodies and antagonists. Flow cytometry and qRT-PCR for macrophage phenotyping. Immunomagnetic macrophage isolation + IL-4 stimulation for opioid peptide secretion measurement.","limitations":"Male mice only — sex differences in immune-opioid interactions likely exist. CCI model is one type of nerve injury. IL-4 injection at injury site is not a practical clinical delivery. Duration of analgesic effect not characterized. Translation to human macrophages needs confirmation."},{"rthcId":"RPEP-05524","title":"Proglucagon-Derived Peptides as Therapeutics.","authors":"Lafferty, Ryan A; O'Harte, Finbarr P M; Irwin, Nigel; Gault, Victor A; Flatt, Peter R","year":2021,"journal":"Frontiers in endocrinology, 12, 689678","doi":"10.3389/fendo.2021.689678","pmid":"34093449","tags":["glp-1","diabetes","weight-loss","gut-healing","next-gen-agonists"],"studyType":"review","evidenceStrength":"n/a-review","keyFinding":"Proglucagon-derived peptide family includes glucagon, GLP-1, GLP-2, oxyntomodulin, glicentin, and GRPP. Each has distinct biology and therapeutic applications. GLP-1 dominates current therapeutics, while oxyntomodulin and glucagon combinations are emerging.","whyItMatters":"Understanding the full proglucagon family explains why multi-receptor agonists (like tirzepatide and cotadutide) are so effective — they harness multiple peptides from the same natural system for synergistic metabolic effects.","specificNumbers":"Covers glucagon, GLP-1, GLP-2, OXM, glicentin, GRPP; approved drugs include semaglutide, liraglutide, exenatide, dulaglutide, teduglutide","methodology":"Comprehensive narrative review of all proglucagon-derived peptides, their processing, biology, physiological functions, and therapeutic applications.","limitations":"Broad review covering extensive biology. Some peptides (glicentin, GRPP) have poorly understood functions. Therapeutic applications are at different stages of development."},{"rthcId":"RPEP-05525","title":"An Empirical Antigen Selection Method Identifies Neoantigens That Either Elicit Broad Antitumor T-cell Responses or Drive Tumor Growth.","authors":"Lam, Hubert; McNeil, Lisa K; Starobinets, Hanna; DeVault, Victoria L; Cohen, Roger B; Twardowski, Przemyslaw; Johnson, Melissa L; Gillison, Maura L; Stein, Mark N; Vaishampayan, Ulka N; DeCillis, Arthur P; Foti, James J; Vemulapalli, Vijetha; Tjon, Emily; Ferber, Kyle; DeOliveira, Daniel B; Broom, Wendy; Agnihotri, Parul; Jaffee, Elizabeth M; Wong, Kwok-Kin; Drake, Charles G; Carroll, Pamela M; Davis, Thomas A; Flechtner, Jessica Baker","year":2021,"journal":"Cancer discovery, 11(3), 696-713","doi":"10.1158/2159-8290.CD-20-0377","pmid":"33504579","tags":["cancer","immune-function","clinical-trials"],"studyType":"clinical-preclinical","evidenceStrength":"moderate","keyFinding":"ATLAS identified both stimulatory and inhibitory neoantigens. In B16F10 melanoma, stimulatory neoantigens protected while inhibitory ones accelerated tumor growth and abolished protective vaccine efficacy. Clinical trial: personalized vaccine well-tolerated, 99% antigen immune response rate.","whyItMatters":"Most neoantigen vaccine efforts use computational prediction alone. This study shows that some predicted neoantigens are actually harmful — making empirical testing essential for safe and effective personalized cancer vaccines.","specificNumbers":"99% peptide antigen response rate; inhibitory neoantigens accelerated tumor growth; CD4+ and CD8+ responses generated","methodology":"ATLAS bioassay: patient tumor mutations expressed in E. coli, pulsed on autologous DCs, tested against patient T cells. Mouse melanoma therapeutic vaccination. Clinical study interim analysis of poly-ICLC adjuvanted personalized neoantigen vaccine in adjuvant setting.","limitations":"Interim clinical analysis (not final results). B16F10 mouse model may not represent all human cancers. ATLAS requires patient blood and tumor samples. The inhibitory mechanism is not fully understood. Time-intensive assay."},{"rthcId":"RPEP-05526","title":"25-Hydroxycholesterol-Conjugated EK1 Peptide with Potent and Broad-Spectrum Inhibitory Activity against SARS-CoV-2, Its Variants of Concern, and Other Human Coronaviruses.","authors":"Lan, Qiaoshuai; Wang, Chao; Zhou, Jie; Wang, Lijue; Jiao, Fanke; Zhang, Yanbo; Cai, Yanxing; Lu, Lu; Xia, Shuai; Jiang, Shibo","year":2021,"journal":"International journal of molecular sciences, 22(21)","doi":"10.3390/ijms222111869","pmid":"34769299","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05527","title":"Imaging therapeutic peptide transport across intestinal barriers.","authors":"Larsen, Jannik Bruun; Taebnia, Nayere; Dolatshahi-Pirouz, Alireza; Eriksen, Anne Zebitz; Hjørringgaard, Claudia; Kristensen, Kasper; Larsen, Nanna Wichmann; Larsen, Niels Bent; Marie, Rodolphe; Mündler, Ann-Kathrin; Parhamifar, Ladan; Urquhart, Andrew James; Weller, Arjen; Mortensen, Kim I; Flyvbjerg, Henrik; Andresen, Thomas Lars","year":2021,"journal":"RSC chemical biology, 2(4), 1115-1143","doi":"10.1039/d1cb00024a","pmid":"34458827","tags":["bioavailability","oral-peptides","peptide-delivery"],"studyType":"review","evidenceStrength":"n/a-review","keyFinding":"Fluorescence imaging provides direct spatiotemporal visualization of peptide transport across intestinal barriers, overcoming the limitations of traditional endpoint assays that only allow indirect study of absorption mechanisms.","whyItMatters":"Making oral peptide drugs viable requires understanding exactly how they cross the gut barrier. Better imaging tools could accelerate development of oral versions of injectable peptide drugs like insulin and semaglutide.","specificNumbers":"Covers in vitro, ex vivo, and in vivo imaging platforms for studying peptide intestinal transport","methodology":"Literature review covering oral peptide pharmacology, intestinal barrier biology, permeability enhancers, and fluorescence imaging methods (in vitro, ex vivo, in vivo platforms) for studying peptide transport.","limitations":"Review article. Does not include new experimental data. Imaging technologies are advancing rapidly."},{"rthcId":"RPEP-05528","title":"Systemic delivery of a specific antibody targeting the pathological N-terminal truncated tau peptide reduces retinal degeneration in a mouse model of Alzheimer's Disease.","authors":"Latina, Valentina; Giacovazzo, Giacomo; Cordella, Federica; Balzamino, Bijorn Omar; Micera, Alessandra; Varano, Monica; Marchetti, Cristina; Malerba, Francesca; Florio, Rita; Ercole, Bruno Bruni; La Regina, Federico; Atlante, Anna; Coccurello, Roberto; Di Angelantonio, Silvia; Calissano, Pietro; Amadoro, Giuseppina","year":2021,"journal":"Acta neuropathologica communications, 9(1), 38","doi":"10.1186/s40478-021-01138-1","pmid":"33750467","tags":["neuroprotection","eye-health","inflammation"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"12A12mAb targeting pathological tau N-terminal fragment improved retinal pathology (APP/Aβ processing, tau phosphorylation, inflammation, synaptic proteins, mitochondrial function, neuronal death) in parallel with hippocampal improvements in Tg2576 AD mice after IV administration.","whyItMatters":"Vision loss in Alzheimer's is underappreciated and untreated. Finding that a single IV tau antibody protects both brain and eyes opens the possibility of treating AD's cognitive AND visual symptoms with one therapy.","specificNumbers":"12A12mAb reduced Aβ, phospho-tau, neuroinflammation, neuronal death; preserved synapses and mitochondria in retina and hippocampus","methodology":"Animal study. Tg2576 Alzheimer's transgenic mice, 6 months old. Intravenous 12A12mAb injection. Retinal and vitreous body analysis for tau truncation, Aβ processing, inflammation, synaptic proteins, microtubule stability, mitochondrial function, and cell death. Brain hippocampal comparison.","limitations":"Tg2576 mouse model — human AD is more complex. Single antibody dose regimen. Long-term visual function not assessed. Translation of tau immunotherapy from mice to humans has been challenging. Eye-specific tau truncation patterns may differ in humans."},{"rthcId":"RPEP-05529","title":"Once-weekly cagrilintide for weight management in people with overweight and obesity: a multicentre, randomised, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial.","authors":"Lau, David C W; Erichsen, Lars; Francisco, Ann Marie; Satylganova, Altynai; le Roux, Carel W; McGowan, Barbara; Pedersen, Sue D; Pietiläinen, Kirsi H; Rubino, Domenica; Batterham, Rachel L","year":2021,"journal":"Lancet (London, England), 398(10317), 2160-2172","doi":"10.1016/S0140-6736(21)01751-7","pmid":"34798060","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05530","title":"Melanocortin receptor activation alleviates amyloid pathology and glial reactivity in an Alzheimer's disease transgenic mouse model.","authors":"Lau, Jackie K Y; Tian, Min; Shen, Yang; Lau, Shun-Fat; Fu, Wing-Yu; Fu, Amy K Y; Ip, Nancy Y","year":2021,"journal":"Scientific reports, 11(1), 4359","doi":"10.1038/s41598-021-83932-4","pmid":"33623128","tags":["melanotan","neuroprotection","inflammation"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"MCR agonist D-Tyr MTII: reduced Aβ accumulation, suppressed neuroinflammation, reduced neurotoxic A1 astrocytes, blunted microglial activation while enhancing plaque-associated microglia, and restored impaired hippocampal transcriptome in APP/PS1 mice.","whyItMatters":"Alzheimer's has no disease-modifying treatment. Melanocortin receptor activation addresses multiple AD pathologies simultaneously — amyloid, inflammation, toxic astrocytes, and disrupted gene expression — a broader approach than single-target drugs.","specificNumbers":"D-Tyr MTII reduced Aβ, A1 astrocytes, microglial activation; enhanced plaque-associated microglia; restored hippocampal transcriptome","methodology":"Animal study. APP/PS1 transgenic Alzheimer's mice. Central (brain) administration of D-Tyr MTII melanocortin agonist. Aβ quantification. Astrocyte/microglia phenotyping. Hippocampal transcriptome analysis. Immunohistochemistry.","limitations":"Central brain administration is not clinically practical. APP/PS1 model may not capture all human AD pathology. Cognitive/behavioral outcomes not reported in this study. Long-term MCR activation effects unknown. MCR agonists have appetite-suppressing effects."},{"rthcId":"RPEP-05531","title":"Polyphosphate coatings: A promising strategy to overcome the polycation dilemma.","authors":"Le, Nguyet-Minh Nguyen; Steinbring, Christian; Le-Vinh, Bao; Jalil, Aamir; Matuszczak, Barbara; Bernkop-Schnürch, Andreas","year":2021,"journal":"Journal of colloid and interface science, 587, 279-289","doi":"10.1016/j.jcis.2020.12.019","pmid":"33360901","tags":["cell-penetrating","peptide-delivery","bioavailability"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Polyphosphate coating of CPP-decorated nanocarriers reversed surface charge from +4.2 to -14.1 mV (tripolyphosphate) or -9.9 mV (phytic acid). Alkaline phosphatase-triggered unmasking increased Caco-2 cell uptake 4-fold with cytoplasmic delivery.","whyItMatters":"The polycation dilemma (needing positive charges for entry but getting toxicity from them) has limited CPP-based drug delivery. This simple coating strategy solves both problems with an enzyme-responsive switch.","specificNumbers":"Zeta potential: +4.2 to -14.1 mV (TPP) or -9.9 mV (phytic acid); 4-fold uptake increase; cytoplasmic distribution confirmed","methodology":"Lab study. Stearic acid-conjugated poly-L-lysine anchored on oil-in-water nanoemulsion. Coated with phytic acid or tripolyphosphate. Zeta potential measured. Alkaline phosphatase-triggered monophosphate release monitored. Cellular uptake and intracellular distribution assessed on Caco-2 cells by confocal microscopy and flow cytometry.","limitations":"In vitro study using Caco-2 cells. No animal testing. Real-world gut conditions (enzymes, mucus, pH) may affect performance."},{"rthcId":"RPEP-05532","title":"Mechanism of Immunoregulatory Properties of Vasoactive Intestinal Peptide in the K/BxN Mice Model of Autoimmune Arthritis.","authors":"Leceta, Javier; Garin, Marina I; Conde, Carmen","year":2021,"journal":"Frontiers in immunology, 12, 701862","doi":"10.3389/fimmu.2021.701862","pmid":"34335612","tags":["neuropeptides","immune-function","inflammation","bone-joint"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"VIP is proposed to treat RA by: (1) inhibiting T cell plasticity toward non-classic Th1 cells, (2) enhancing follicular regulatory T cell (Tfr) activity, and (3) consequently reducing systemic pathogenic autoantibody titers that drive arthritis.","whyItMatters":"Current RA treatments suppress the whole immune system, increasing infection risk. VIP-based therapy could specifically reprogram the disease-causing immune cells while leaving protective immunity intact.","specificNumbers":"Proposed: VIP inhibits non-classic Th1 plasticity, enhances Tfr activity, reduces anti-GPI antibodies","methodology":"Hypothesis and theory article. Proposes mechanisms for VIP immunoregulatory properties in the K/BxN rheumatoid arthritis mouse model based on known VIP biology, T cell plasticity, and follicular regulatory T cell function.","limitations":"Hypothesis/theory article — proposed mechanisms not experimentally validated in this paper. VIP's short half-life limits clinical delivery. K/BxN model may not capture all aspects of human RA. Systemic VIP has cardiovascular effects (vasodilation)."},{"rthcId":"RPEP-05533","title":"Interplay among Conformation, Intramolecular Hydrogen Bonds, and Chameleonicity in the Membrane Permeability and Cyclophilin A Binding of Macrocyclic Peptide Cyclosporin O Derivatives.","authors":"Lee, Dongjae; Lee, Sungjin; Choi, Jieun; Song, Yoo-Kyung; Kim, Min Ju; Shin, Dae-Seop; Bae, Myung Ae; Kim, Yong-Chul; Park, Chin-Ju; Lee, Kyeong-Ryoon; Choi, Jun-Ho; Seo, Jiwon","year":2021,"journal":"Journal of medicinal chemistry, 64(12), 8272-8286","doi":"10.1021/acs.jmedchem.1c00211","pmid":"34096287","tags":["cyclic-peptides","bioavailability","peptide-design"],"studyType":"preclinical","evidenceStrength":"moderate","keyFinding":"Cyclosporin O derivatives demonstrated that intramolecular hydrogen bonds and conformational chameleonicity determine membrane permeability and cyclophilin A binding. Conformation-permeability-binding relationships were mapped with PK profiling.","whyItMatters":"Oral delivery of macrocyclic peptides is a major pharmaceutical goal. Understanding the conformational rules that govern membrane permeability enables rational design of orally bioavailable peptide drugs for currently undruggable targets.","specificNumbers":"CsO F=12% oral bioavailability; minimal CypA binding; higher plasma concentration than CsA; less chameleonic in polar media","methodology":"Structure-property study. Cyclosporin O and derivatives CP1-3. Conformational analysis. Membrane permeability assessment. Cyclophilin A binding. Pharmacokinetic profiling. Intramolecular hydrogen bond characterization.","limitations":"Limited to cyclosporin O scaffold. Rules may not generalize to all macrocyclic peptides. PK profiling scope not detailed. Cell-based permeability may not match in vivo absorption."},{"rthcId":"RPEP-05534","title":"Intra-Articular Injection of BPC 157 for Multiple Types of Knee Pain.","authors":"Lee, Edwin; Padgett, Blake","year":2021,"journal":"Alternative therapies in health and medicine, 27(4), 8-13","doi":null,"pmid":"34324435","tags":["bpc-157","bone-joint","clinical-trials"],"studyType":"retrospective","evidenceStrength":"weak","keyFinding":"Overall 87.5% (14/16) significant pain improvement. BPC-157 alone: 91.6% (11/12) improved. BPC-157 + TB4: 75% (3/4) improved. Multiple knee pathologies responded. 6-month to 1-year follow-up showed sustained benefit.","whyItMatters":"This is one of the only published human studies of BPC-157 for joint pain. The high response rate across multiple knee conditions suggests BPC-157 may be a regenerative alternative to steroid injections, which provide temporary relief but can damage cartilage long-term.","specificNumbers":"14/16 (87.5%) improved; BPC-157 alone: 11/12 (91.6%); BPC-157+TB4: 3/4 (75%); 6mo-1yr follow-up","methodology":"Retrospective chart review. 17 patients, 16 contacted for follow-up. Institute for Hormonal Balance, Orlando, Florida. 2019-2020. Intra-articular BPC-157 ± TB4 injection. Phone survey for pain rating, duration of relief, and degree of improvement. No standardized outcome tools.","limitations":"Very small retrospective study (16 patients). No control group or blinding. Self-reported outcomes by phone without validated measures. Single clinic. No imaging to document tissue repair. Potential placebo effect. Selection bias."},{"rthcId":"RPEP-05535","title":"Di-(2-ethylhexyl) phthalate-induced tumor growth is regulated by primary cilium formation via the axis of H2O2 production-thymosin beta-4 gene expression.","authors":"Lee, Jae-Wook; Thuy, Pham Xuan; Han, Hae-Kyoung; Moon, Eun-Yi","year":2021,"journal":"International journal of medical sciences, 18(5), 1247-1258","doi":"10.7150/ijms.53595","pmid":"33526986","tags":["thymosin-beta-4","cancer"],"studyType":"animal","evidenceStrength":"preliminary","keyFinding":"DEHP increased TB4 expression, driving primary cilia formation and H2O2 production in a positive feedback loop. TB4 overexpression enhanced DEHP-induced tumor growth. TB4 knockdown reduced cilia, H2O2, and tumor viability.","whyItMatters":"Plastic chemicals are everywhere. Understanding how DEHP promotes cancer through TB4 could lead to biomarkers for cancer risk from environmental plastic exposure.","specificNumbers":"DEHP increased TB4, cilia, and H2O2; TB4 siRNA reduced all three; TB4 overexpression enhanced DEHP tumor growth; catalase but not mito-TEMPO blocked H2O2","methodology":"In vitro study using HeLa cells and HEK293 cells. In vivo melanoma model in mice (B16 cells, IP DEHP). Measured TB4 expression, primary cilia formation, ROS/H2O2 production. Used siRNA knockdown, TB4 overexpression, and inhibitors (catalase, ciliobrevin A, mito-TEMPO).","limitations":"Used HeLa cells and mouse melanoma model. The TB4-cilia-DEHP connection may not apply equally to all cancer types. DEHP doses may not reflect typical human exposure."},{"rthcId":"RPEP-05536","title":"Development of High Affinity Calcitonin Analog Fragments Targeting Extracellular Domains of Calcitonin Family Receptors.","authors":"Lee, Sangmin","year":2021,"journal":"Biomolecules, 11(9)","doi":"10.3390/biom11091364","pmid":"34572577","tags":["peptide-design","bone-joint","diabetes"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Three mutations (N26D, S29P, P32HYP) in sCT(22-32) increased CTR ECD affinity 21-fold. The mutated fragment also retained high affinity for all 3 AMY receptor ECD types (CTR:RAMP1, CTR:RAMP2, CTR:RAMP3).","whyItMatters":"Osteoporosis and diabetes often co-occur in aging. A single peptide fragment that engages both calcitonin (bone) and amylin (metabolic) receptors could simplify treatment for elderly patients with both conditions.","specificNumbers":"21-fold affinity increase; mutations N26D, S29P, P32HYP; retained binding to AMY1, AMY2, AMY3 receptor ECDs","methodology":"Peptide biochemistry study. Purified CTR and AMY receptor extracellular domains (ECDs). Fluorescence polarization/anisotropy peptide binding assays. Systematic mutation screening of sCT(22-32) fragment.","limitations":"In vitro binding study using isolated receptor domains — full receptor activation and in vivo efficacy not tested. Short fragment may not fully activate receptors. Pharmacokinetics of the 11-mer peptide unknown. Clinical translation requires substantial development."},{"rthcId":"RPEP-05537","title":"Corneal lymphangiogenesis in dry eye disease is regulated by substance P/neurokinin-1 receptor system through controlling expression of vascular endothelial growth factor receptor 3.","authors":"Lee, Seok Jae; Im, Sang-Taek; Wu, Jun; Cho, Chang Sik; Jo, Dong Hyun; Chen, Yihe; Dana, Reza; Kim, Jeong Hun; Lee, Sang-Mok","year":2021,"journal":"The ocular surface, 22, 72-79","doi":"10.1016/j.jtos.2021.07.003","pmid":"34311077","tags":["neuropeptides","eye-health","inflammation"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"SP/NK1R system promotes corneal lymphangiogenesis in DED by upregulating VEGFR3 expression on HDLECs. DED mouse model confirmed NK1R-dependent lymphatic vessel invasion. NK1R antagonism could inhibit pathologic lymphangiogenesis.","whyItMatters":"Dry eye affects hundreds of millions worldwide. Current treatments manage symptoms but don't address the underlying lymphatic vessel invasion that perpetuates inflammation. Blocking SP/NK1R could break this cycle.","specificNumbers":"NK1R antagonist suppressed VEGF-C, VEGF-D, VEGFR3; improved fluorescein staining and tear production in DED mice","methodology":"In vitro + animal study. Human dermal lymphatic endothelial cells (HDLECs): immunocytochemistry, angiogenesis assay, Western blot for SP/NK1R effects on VEGFR3. DED induced in wild-type C57BL/6 mice. Corneal lymphangiogenesis assessment.","limitations":"Mouse DED model may not replicate all aspects of human dry eye. Human cell data is in vitro. NK1R antagonist treatment not tested in the DED model. Clinical translation needs confirmation."},{"rthcId":"RPEP-05538","title":"A deep-learning framework for multi-level peptide-protein interaction prediction.","authors":"Lei, Yipin; Li, Shuya; Liu, Ziyi; Wan, Fangping; Tian, Tingzhong; Li, Shao; Zhao, Dan; Zeng, Jianyang","year":2021,"journal":"Nature communications, 12(1), 5465","doi":"10.1038/s41467-021-25772-4","pmid":"34526500","tags":["peptide-design","receptor-signaling"],"studyType":"computational","evidenceStrength":"moderate","keyFinding":"CAMP deep learning framework successfully predicted binary peptide-protein interactions and identified binding residues along peptides, outperforming state-of-the-art methods without requiring 3D structure data.","whyItMatters":"Identifying which peptides bind which proteins is essential for drug discovery. A tool that works without 3D structures dramatically expands the scope of peptides that can be studied.","specificNumbers":"Outperformed state-of-the-art on binary interaction prediction; identifies binding residues without 3D structure","methodology":"Computational study. Developed deep learning framework (CAMP) for multi-level prediction: binary interaction and binding residue identification. Trained and validated on peptide-protein interaction datasets. Benchmarked against existing methods.","limitations":"Computational predictions need experimental validation. Performance may vary for unusual peptide types not well represented in training data."},{"rthcId":"RPEP-05539","title":"The Influence of Selank on the Level of Cytokines Under the Conditions of \"Social\" Stress.","authors":"Leonidovna, Yasenyavskaya A; Aleksandrovna, Samotrueva M; Aleksandrovna, Tsibizova A; Aleksandrovna, Bashkina O; Fedorovich, Myasoedov N; Aleksandrovna, Andreeva L","year":2021,"journal":"Current reviews in clinical and experimental pharmacology, 16(2), 162-167","doi":"10.2174/1574884715666200704152810","pmid":"32621722","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05540","title":"Parathyroid hormone.","authors":"Leung, Edward Ki Yun","year":2021,"journal":"Advances in clinical chemistry, 101, 41-93","doi":"10.1016/bs.acc.2020.06.005","pmid":"33706890","tags":["parathyroid-hormone","bone-health","calcium-regulation"],"studyType":"Review","evidenceStrength":"Review/Reference","keyFinding":"Parathyroid hormone (PTH) is the master regulator of calcium and phosphate balance in the body, acting through three main pathways: increasing calcium reabsorption in the kidneys while blocking phosphate reabsorption, stimulating vitamin D activation to boost calcium absorption from food, and increasing bone resorption to release calcium and phosphate into the blood.\n\nParathyroid diseases can arise from genetic mutations affecting gland formation, hormone synthesis or secretion, or gland destruction. Treatment options range from surgical removal of overactive parathyroid tissue to hormone replacement, vitamin D supplementation, phosphate binders, and receptor activators. The review also highlights that current lab tests for PTH can be inaccurate due to interference from hormone fragments, phosphorylation, and amino acid oxidation.","whyItMatters":"PTH is one of the most important peptide hormones in the body, and its dysregulation underlies a wide range of conditions from osteoporosis to kidney stones to chronic kidney disease–related bone disorders. Understanding PTH biology is essential for anyone studying peptide therapeutics for bone health, including teriparatide and abaloparatide. The diagnostic challenges highlighted in this review — where lab tests can over- or underestimate active PTH — have real clinical consequences for patients being diagnosed and treated for parathyroid disorders.","specificNumbers":"3 major PTH pathways · kidney, gut, and bone target organs · multiple immunoassay interference sources","methodology":"This is a comprehensive narrative review published as a chapter in Advances in Clinical Chemistry, summarizing the current understanding of PTH biology, parathyroid disease genetics, therapeutic options, and laboratory diagnostic methods.","limitations":"As a narrative review rather than a systematic review, the study selection may not be exhaustive. The abstract does not provide specific quantitative data on treatment outcomes or diagnostic test performance metrics. The review focuses broadly rather than deeply on any single aspect of PTH biology."},{"rthcId":"RPEP-05541","title":"A Clinician's Guide to the Treatment of Endometriosis with Elagolix.","authors":"Leyland, Nicholas; Estes, Stephanie J; Lessey, Bruce A; Advincula, Arnold P; Taylor, Hugh S","year":2021,"journal":"Journal of women's health (2002), 30(4), 569-578","doi":"10.1089/jwh.2019.8096","pmid":"32975461","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05542","title":"Apoptosis-inducing activity of synthetic hydrocarbon-stapled peptides in H358 cancer cells expressing KRASG12C.","authors":"Li, Cuicui; Zhao, Ni; An, Luyan; Dai, Zhen; Chen, Xiaoyi; Yang, Fan; You, Qidong; Di, Bin; Hu, Chi; Xu, Lili","year":2021,"journal":"Acta pharmaceutica Sinica. B, 11(9), 2670-2684","doi":"10.1016/j.apsb.2021.06.013","pmid":"34589388","tags":["cyclic-peptides","cancer","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Stapled peptide 3 bound KRASG12C with modest affinity, induced G2/M arrest and apoptosis in H358 cells by disrupting RAF/MEK/ERK signaling, with superior protease resistance and plasma/microsomal stability compared to the parent peptide SAH-SOS1A.","whyItMatters":"KRAS mutations have been considered undruggable for decades. Stapled peptides offer a new approach that could complement small molecule KRAS inhibitors like sotorasib.","specificNumbers":"Peptide 3: shorter, equivalent anti-tumor activity to SAH-SOS1A; G2/M arrest + apoptosis; resistant to trypsin/chymotrypsin; stable in plasma and liver microsomes","methodology":"In vitro study. Synthesized hydrocarbon-stapled peptides based on SAH-SOS1A. Tested binding, cell growth inhibition, cell cycle, and apoptosis in KRASG12C-expressing H358 cells. Verified mechanism by genomics and proteomics. Assessed protease resistance and metabolic stability.","limitations":"In vitro study using one cell line (H358). No animal studies. KRASG12C binding affinity described as 'modest.' In vivo efficacy needs testing."},{"rthcId":"RPEP-05543","title":"Multifunctional nanoplatforms as cascade-responsive drug-delivery carriers for effective synergistic chemo-photodynamic cancer treatment.","authors":"Li, Fan; Liang, Yan; Wang, Miaochen; Xu, Xing; Zhao, Fen; Wang, Xu; Sun, Yong; Chen, Wantao","year":2021,"journal":"Journal of nanobiotechnology, 19(1), 140","doi":"10.1186/s12951-021-00876-7","pmid":"34001157","tags":["cell-penetrating","cyclic-peptides","cancer","peptide-delivery"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"pH cascade-responsive cRGD-targeted micellar nanoplatform achieved nucleus-targeted co-delivery of chemotherapy drug GNA002 and photodynamic therapy agent, enabling synergistic chemo-photodynamic cancer treatment.","whyItMatters":"Combining chemotherapy with photodynamic therapy attacks cancer through two mechanisms. Delivering both to the nucleus — where DNA is — maximizes damage to cancer cells while the RGD peptide targeting minimizes damage to healthy tissue.","specificNumbers":"cRGD targeting; pH-responsive shell; R6 nuclear penetration; GNA002 + porphyrin PDT; 532 nm laser; high tumor suppression in vivo","methodology":"Nanoformulation study. Cyclic RGD peptide-decorated micelles with porphyrin-GNA002 hydrophobic core. pH-responsive behavior characterization. Tumor targeting, cellular uptake, nuclear localization, PDT efficacy, and synergistic cancer cell killing assessed.","limitations":"In vitro studies primarily. Light penetration limits PDT to superficial tumors. Manufacturing complexity of multi-component nanoplatforms. Reproducibility and clinical scalability challenges."},{"rthcId":"RPEP-05544","title":"Acupuncture Regulates Serum Differentially Expressed Proteins in Patients with Chronic Atrophic Gastritis: A Quantitative iTRAQ Proteomics Study.","authors":"Li, Feng; Yang, Bai; Liu, Yanan; Tang, Tianying; Wang, Cun; Li, Mei; Lv, Siyi; Qi, Qin; Liu, Huirong; Shi, Zheng; Wu, Huangan; Wang, Xiaomei","year":2021,"journal":"Evidence-based complementary and alternative medicine : eCAM, 2021, 9962224","doi":"10.1155/2021/9962224","pmid":"34234838","tags":["thymosin-beta-4","gut-healing","inflammation"],"studyType":"observational","evidenceStrength":"weak","keyFinding":"CAG patients showed upregulated actin-binding proteins (thymosin beta-4, tropomyosin-4, profilin-1, transgelin-2) and downregulated Notch2/3. Acupuncture treatment normalized these protein levels toward healthy controls.","whyItMatters":"Chronic atrophic gastritis is a precancerous condition. Understanding which proteins change and how acupuncture affects them could inform both diagnosis and treatment monitoring.","specificNumbers":"816 proteins identified; TB4, tropomyosin-4, profilin-1, transgelin-2 upregulated; Notch2/3 downregulated; 6 proteins validated by ELISA","methodology":"Comparative proteomics study. Peripheral sera from 8 healthy, 8 NAG, 8 CAG, and 8 CAG+acupuncture patients analyzed by iTRAQ labeling and 2D-LC-MS/MS. 6 proteins validated by ELISA.","limitations":"Very small sample size (8 per group). No randomization or blinding for acupuncture treatment. Correlation does not prove causation."},{"rthcId":"RPEP-05545","title":"Exenatide improves random-pattern skin flap survival via TFE3 mediated autophagy augment.","authors":"Li, Jiafeng; Chen, Huanwen; Lou, Junsheng; Bao, Guodong; Wu, Chenyu; Lou, Zhiling; Wang, Xingyu; Ding, Jian; Li, Zhijie; Xiao, Jian; Xu, Huazi; Gao, Weiyang; Zhou, Kailiang","year":2021,"journal":"Journal of cellular physiology, 236(5), 3641-3659","doi":"10.1002/jcp.30102","pmid":"33044023","tags":["exenatide","glp-1","wound-healing"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"Exenatide improved random skin flap survival by activating autophagy via TFE3 nuclear translocation through AMPK-SKP2-CARM1 and AMPK-mTOR signaling. Autophagy inhibition reversed all benefits.","whyItMatters":"Skin flap failure is a common surgical complication. A repurposed diabetes drug that prevents flap necrosis through autophagy could be immediately useful in reconstructive surgery.","specificNumbers":"Exenatide improved viability, angiogenesis; reduced oxidative stress, pyroptosis; autophagy inhibitors reversed all; TFE3 nuclear translocation via AMPK-SKP2-CARM1 and AMPK-mTOR","methodology":"Animal study in male C57BL/6 mice. Random-pattern dorsal skin flap model. Exenatide treatment. Co-treatment with autophagy inhibitors (3-MA, chloroquine). Assessed flap viability, angiogenesis, oxidative stress, pyroptosis, autophagy markers, and TFE3 nuclear translocation.","limitations":"Mouse study. Flap model may not fully replicate human surgical conditions. Specific exenatide dosing for this application needs optimization."},{"rthcId":"RPEP-05546","title":"Efficacy and safety of the glucagon-like peptide-1 receptor agonist oral semaglutide in patients with type 2 diabetes mellitus: A systematic review and meta-analysis.","authors":"Li, Jingxin; He, Ke; Ge, Jun; Li, Caixia; Jing, Zeng","year":2021,"journal":"Diabetes research and clinical practice, 172, 108656","doi":"10.1016/j.diabres.2021.108656","pmid":"33434602","tags":["semaglutide","diabetes","weight-loss","clinical-trials"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Oral semaglutide vs placebo: reduced HbA1c, weight, FPG, SMPG, serious adverse events, and all-cause death. Vs active comparators: reduced HbA1c, weight, SMPG. No increased hypoglycemia, MI, HF, stroke, or pancreatitis. Increased nausea, diarrhea, vomiting. 10 RCTs, 8,536 patients.","whyItMatters":"The first oral GLP-1 drug eliminates the injection barrier that prevents many patients from using this effective drug class. This meta-analysis confirms oral semaglutide is both effective and safe — potentially expanding GLP-1 use to millions more diabetes patients.","specificNumbers":"10 RCTs; 8,536 patients; reduced HbA1c, weight, FPG vs placebo/comparators; reduced all-cause death vs placebo; increased nausea/diarrhea/vomiting","methodology":"Systematic review and meta-analysis. 10 RCTs from PubMed, Embase, Cochrane Library, ClinicalTrials.gov. 8,536 patients. Oral semaglutide vs placebo and active comparators. Risk ratios and mean differences with 95% CI.","limitations":"Meta-analysis heterogeneity between trials. Some comparators tested in single trials. Active comparator doses may not have been optimal in all studies. Mortality benefit seen vs placebo may reflect the sicker control population. Follow-up durations varied."},{"rthcId":"RPEP-05547","title":"A novel biocomposite scaffold with antibacterial potential and the ability to promote bone repair.","authors":"Li, Kai; Guo, Ai; Ran, Qichun; Tian, Hongchuan; Du, Xing; Chen, Sinan; Wen, Yafeng; Tang, Yue; Jiang, Dianming","year":2021,"journal":"Journal of biomaterials applications, 36(3), 474-480","doi":"10.1177/0885328221994448","pmid":"33596708","tags":["peptide-design","bone-joint","antimicrobial-peptides","peptide-delivery"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Novel biocomposite scaffold with integrated antibacterial peptide activity demonstrated both bone regeneration capability and infection prevention, addressing the dual challenge of infected bone defects.","whyItMatters":"Infected bone defects are one of the most difficult problems in orthopedic surgery. A scaffold that simultaneously fights bacteria and grows new bone could prevent the multiple surgeries currently needed to first clear infection and then repair bone.","specificNumbers":"RADA-CPC enhanced osteoblast proliferation/differentiation/mineralization; sustained ciprofloxacin release","methodology":"Biomaterials study. Biocomposite scaffold fabrication with antibacterial peptide incorporation. Antibacterial activity testing. Bone regeneration assessment (biocompatibility, cell adhesion, osteogenic potential).","limitations":"In vitro characterization primarily. In vivo bone regeneration and infection prevention in animal models needs confirmation. Long-term peptide activity on scaffold unknown. Manufacturing scalability not addressed."},{"rthcId":"RPEP-05548","title":"Self-Assembly Dipeptide Hydrogel: The Structures and Properties.","authors":"Li, Liangchun; Xie, Li; Zheng, Renlin; Sun, Rongqin","year":2021,"journal":"Frontiers in chemistry, 9, 739791","doi":"10.3389/fchem.2021.739791","pmid":"34540806","tags":["peptide-design","peptide-delivery"],"studyType":"review","evidenceStrength":"n/a-review","keyFinding":"Dipeptides are the shortest self-assembling peptide motifs capable of hydrogel formation. They create diverse nanostructures with controllable properties and biocompatibility for biomedical applications despite minimal complexity.","whyItMatters":"Simpler = cheaper and more practical. Dipeptide hydrogels could bring peptide biomaterial technology from specialized labs to routine clinical use by dramatically reducing cost and manufacturing complexity.","specificNumbers":"Three modification strategies; β-sheet/π-stacking assembly; nanofiber hydrogels","methodology":"Narrative review of dipeptide self-assembly mechanisms, structural characterization, material properties, and biomedical applications.","limitations":"Brief review covering general principles. Specific biomedical applications not deeply analyzed. Mechanical properties may be inferior to longer peptide or polymer hydrogels for some applications."},{"rthcId":"RPEP-05549","title":"Lipophilic Salts and Lipid-Based Formulations: Enhancing the Oral Delivery of Octreotide.","authors":"Li, Peng; Ford, Leigh; Haque, Shadabul; McInerney, Mitchell P; Williams, Hywel D; Scammells, Peter J; Thompson, Philip E; Jannin, Vincent; Porter, Christopher J H; Benameur, Hassan; Pouton, Colin W","year":2021,"journal":"Pharmaceutical research, 38(6), 1125-1137","doi":"10.1007/s11095-021-03063-3","pmid":"34100217","tags":["oral-peptides","bioavailability","peptide-delivery"],"studyType":"preclinical","evidenceStrength":"moderate","keyFinding":"Lipophilic salt forms of octreotide in lipid-based formulations improved enzymatic stability in GI lumen and intestinal membrane permeability, addressing both major barriers to oral peptide delivery.","whyItMatters":"Octreotide injections are burdensome for patients with chronic conditions. An oral formulation would dramatically improve quality of life and treatment adherence for patients needing long-term octreotide therapy.","specificNumbers":"OCT.DoS2 + SEDDS higher absorption; no permeability increase in Caco-2/in situ; reduced enzymatic degradation; prolonged lipid retention","methodology":"Pharmaceutical formulation study. Lipophilic counter-ion pairing with octreotide. Lipid-based formulation optimization. Enzymatic stability testing. Intestinal permeability assessment.","limitations":"In vitro formulation study. In vivo oral bioavailability not tested. Lipid-based formulations face stability and manufacturing challenges. Food effects on absorption unknown."},{"rthcId":"RPEP-05550","title":"P22 virus-like particles as an effective antigen delivery nanoplatform for cancer immunotherapy.","authors":"Li, Wenjing; Jing, Zhe; Wang, Shuqing; Li, Qiyu; Xing, Yutong; Shi, Haobo; Li, Shuang; Hong, Zhangyong","year":2021,"journal":"Biomaterials, 271, 120726","doi":"10.1016/j.biomaterials.2021.120726","pmid":"33636548","tags":["cancer","immune-function","peptide-delivery"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"P22 virus-like particles displaying B-cell epitope peptides (VLP-OVAB) induced antibody titers as high as 5.0 × 10⁵ against the peptide antigen. VLPs displaying T-cell epitope peptides (VLP-OVAT) induced highly effective cross-presentation and strongly activated cytotoxic T lymphocyte (CTL) responses.\n\nIn mouse tumor models, VLP-OVAT significantly inhibited tumor growth by increasing proportions of CD4+ T cells, CD8+ T cells, and effector memory T cells (TEM) among tumor-infiltrating lymphocytes while lowering the proportion of myeloid-derived suppressor cells (MDSCs) that help tumors evade the immune system.","whyItMatters":"Personalized cancer vaccines need to efficiently deliver neoantigen peptides to trigger strong immune responses, but current delivery methods often produce weak T-cell activation. VLPs offer a promising platform because they naturally stimulate the immune system, have a defined structure, and are biocompatible — potentially providing a standardized way to create individualized cancer vaccines based on each patient's tumor mutations.","specificNumbers":"VLP-OVAB: Ab titer 5×10^5; VLP-OVAT: strong CTL activation; significant tumor inhibition; increased CD4+/CD8+/TEM; reduced MDSCs","methodology":"Researchers genetically fused ovalbumin B-cell and T-cell epitope peptides to the coat protein of P22 bacteriophage, creating two types of virus-like particles (VLP-OVAB and VLP-OVAT). They measured antibody responses, cross-presentation efficiency, and CTL activation in vitro. Therapeutic efficacy was tested in mouse tumor models, with analysis of tumor growth rates and immune cell profiling of tumor-infiltrating lymphocytes and splenocytes.","limitations":"The study used ovalbumin as a model antigen rather than actual tumor neoantigens, so it remains unclear how well this platform would work with real patient-specific mutations. All experiments were conducted in mice, and the immune environment in human tumors is considerably more complex. Long-term safety data and manufacturing scalability for personalized VLP vaccines were not addressed."},{"rthcId":"RPEP-05551","title":"De novo design of self-assembly hydrogels based on Fmoc-diphenylalanine providing drug release.","authors":"Li, Xiang; Zhang, Huijun; Liu, Lingyan; Cao, Chunyan; Wei, Peng; Yi, Xin; Zhou, Yifeng; Lv, Qingyang; Zhou, Dongfang; Yi, Tao","year":2021,"journal":"Journal of materials chemistry. B, 9(41), 8686-8693","doi":"10.1039/d1tb01628h","pmid":"34617098","tags":["peptide-design","peptide-delivery","cancer"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Fmoc-FFRRVR gelated in 2 seconds under mild conditions, forming elastic, reversible, injectable β-sheet nanofiber hydrogels capable of sustained doxorubicin release with maintained biocompatibility.","whyItMatters":"Ultra-fast gelling, injectable hydrogels are ideal for local drug delivery in cancer. A 2-second gel time means it can be injected as liquid and solidify immediately at the tumor site.","specificNumbers":"2s gelation; β-sheet nanofibers via π-stacking; elastic, reversible, injectable; sustained doxorubicin release","methodology":"Lab study. Designed and synthesized Fmoc-FFRRVR. Characterized self-assembly by CD, fluorescence spectroscopy, and rheology. Loaded with doxorubicin. Tested drug release kinetics and cell viability/proliferation.","limitations":"In vitro study. No animal tumor models tested. Long-term stability and drug release kinetics in vivo unknown."},{"rthcId":"RPEP-05552","title":"Gender-associated difference following COVID-19 virus infection: Implications for thymosin alpha-1 therapy.","authors":"Li, Xin; Liu, Lancong; Yang, Yi; Yang, Xuefeng; Wang, Cencen; Li, Yan; Ge, Yanyan; Shi, Yuxin; Lv, Ping; Zhou, Hua; Luo, Pei; Huang, Shilong","year":2021,"journal":"International immunopharmacology, 90, 107022","doi":"10.1016/j.intimp.2020.107022","pmid":"33160854","tags":["thymosin-alpha-1","immune-function"],"studyType":"clinical trial","evidenceStrength":"moderate","keyFinding":"Tα1 treatment (1.6 mg SC × 15 days) in 78 COVID-19 patients showed gender-dependent immune responses: males had higher CRP and IL-6 but lower PCT post-treatment. Significant variability in lymphocyte subpopulations between Tα1-treated males and females.","whyItMatters":"Understanding sex-specific immune responses to COVID-19 treatment could improve outcomes. If Tα1 works differently in men and women, dosing and treatment duration might need gender-specific optimization.","specificNumbers":"N=127; 78 treated, 49 controls; 1.6 mg Tα1 subcutaneous; 15-day treatment; 42.52% female","methodology":"Retrospective clinical study. 127 COVID-19 patients (42.52% female), Wuhan Union Hospital. 78 received Tα1 1.6mg SC × 15 days + supportive care. 49 controls received supportive care only. CRP, PCT, IL-6, lymphocyte subpopulations, and symptom analysis by gender.","limitations":"Retrospective study without randomization blinding. Small sample (127 total). Single center in Wuhan during early pandemic. Standard care may have varied. Gender as a binary variable may oversimplify biological sex differences. Mortality and clinical outcome data limited."},{"rthcId":"RPEP-05553","title":"Stimuli-responsive biphenyl-tripeptide supramolecular hydrogels as biomimetic extracellular matrix scaffolds for cartilage tissue engineering.","authors":"Li, Xing; Bian, Shaoquan; Zhao, Mingda; Han, Xiaowen; Liang, Jie; Wang, Kefeng; Jiang, Qing; Sun, Yong; Fan, Yujiang; Zhang, Xingdong","year":2021,"journal":"Acta biomaterialia, 131, 128-137","doi":"10.1016/j.actbio.2021.07.007","pmid":"34245894","tags":["peptide-drug-design","collagen-peptides"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"BPAA-βAFF hydrogel formed nanofibers at 0.023 wt% concentration and promoted cartilage cell growth and matrix production in lab tests.","whyItMatters":"Cartilage does not heal well on its own. A simple, low-cost gel that mimics cartilage structure could advance tissue engineering for joint repair.","specificNumbers":"MGC 0.4 mM (0.023 wt%); 8-10 nm nanotubes/nanofibers; 8.2 KPa storage modulus","methodology":"Lab study testing biphenyl-tripeptide compounds with different amino acid arrangements. Evaluated gelation properties, nanostructure, cell compatibility with L929 cells, and cartilage cell behavior in vitro.","limitations":"Only tested in lab dishes, not in living animals. Long-term stability and performance in actual joints are unknown."},{"rthcId":"RPEP-05554","title":"Ghrelin Based Therapy of Metabolic Diseases.","authors":"Liang, Yuan; Yin, Wenzhen; Yin, Yue; Zhang, Weizhen","year":2021,"journal":"Current medicinal chemistry, 28(13), 2565-2576","doi":"10.2174/0929867327666200615152804","pmid":"32538716","tags":["ghrelin","ghsr-receptor","obesity-metabolism"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Ghrelin-GHSR targeting strategies include ghrelin-neutralizing antibodies/spiegelmers, GHSR antagonists/inverse agonists, GOAT enzyme inhibitors, and approaches to decrease ghrelin synthesis. Animal efficacy demonstrated for multiple compounds.","whyItMatters":"Ghrelin is the only known circulating appetite-stimulating hormone. Blocking it complements GLP-1 drugs (which enhance satiety), potentially enabling combination therapy for greater weight loss.","specificNumbers":"Ghrelin: 28 amino acids; secreted by gastric X/A cells; endogenous GHSR ligand","methodology":"Narrative review of therapeutic strategies targeting the ghrelin-GHSR pathway for obesity and metabolic diseases.","limitations":"Mostly preclinical compounds. No ghrelin-targeting drugs approved for obesity. Safety of chronic hunger hormone suppression unclear."},{"rthcId":"RPEP-05555","title":"Co-assembled nanocomplexes of peptide neoantigen Adpgk and Toll-like receptor 9 agonist CpG ODN for efficient colorectal cancer immunotherapy.","authors":"Liang, Zhaoyuan; Cui, Xinyue; Yang, Liqun; Hu, Qin; Li, Danyang; Zhang, Xiaofei; Han, Lu; Shi, Siwei; Shen, Yurong; Zhao, Weijian; Ju, Qi; Deng, Xiongwei; Wu, Yan; Sheng, Wang","year":2021,"journal":"International journal of pharmaceutics, 608, 121091","doi":"10.1016/j.ijpharm.2021.121091","pmid":"34555477","tags":["peptide-drug-design","immune-function"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Co-assembled nanocomplexes of neoantigen peptide Adpgk with TLR agonist overcame poor immunogenicity of free peptides, efficiently eliciting high-intensity CTL responses through simultaneous antigen-adjuvant delivery to immune cells.","whyItMatters":"The gap between identifying cancer neoantigens and making effective vaccines is often the delivery. Co-assembled nanocomplexes provide a simple, scalable solution that could make personalized cancer vaccines more effective.","specificNumbers":"~175 nm particles; 10K-Adpgk cationic polypeptide; TLR-9 agonist CpG ODN; prophylactic and therapeutic models","methodology":"Nanotechnology and immunology study. Self-assembly of neoantigen peptide with TLR agonist into nanocomplexes. Characterization of nanostructure formation. CTL response assessment in vitro and in vivo. Comparison with free peptide + adjuvant.","limitations":"Single neoantigen tested. In vivo tumor rejection data not detailed. Manufacturing consistency of self-assembled nanocomplexes needs verification. Clinical translation challenges remain."},{"rthcId":"RPEP-05556","title":"Structural optimization of reversible dibromomaleimide peptide stapling.","authors":"Lindsey-Crosthwait, Ayanna; Rodriguez-Lema, Diana; Walko, Martin; Pask, Christopher M; Wilson, Andrew J","year":2021,"journal":"Peptide science (Hoboken, N.J.), 113(1), e24157","doi":"10.1002/pep2.24157","pmid":"34938942","tags":["peptide-drug-design","stapled-peptides"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Optimized reversible dibromomaleimide stapling of peptides using native Cys/homoCys at i, i+4 positions. Structural analysis revealed conformation-activity relationships for α-helical peptide stabilization targeting protein-protein interactions.","whyItMatters":"Reversible stapling adds a design dimension: peptides can be stabilized for delivery but potentially unstapled at the target site. This \"smart stapling\" concept could improve peptide drug efficacy and reduce off-target effects.","specificNumbers":"i, i+4 spacing; Ac-X1AAAX5-NH2 model; optimal X1=L-Cys, X5=L-hCys","methodology":"Medicinal chemistry study. Dibromomaleimide stapling of peptides with native cysteine residues. Structural characterization (NMR, CD). Binding affinity assessment. Reversibility demonstration.","limitations":"Structural optimization study — therapeutic efficacy not tested. Reversibility conditions may not match biological requirements. Limited peptide sequences tested."},{"rthcId":"RPEP-05557","title":"PET Diagnostic Molecules Utilizing Multimeric Cyclic RGD Peptide Analogs for Imaging Integrin αvβ3 Receptors.","authors":"Liolios, Christos; Sachpekidis, Christos; Kolocouris, Antonios; Dimitrakopoulou-Strauss, Antonia; Bouziotis, Penelope","year":2021,"journal":"Molecules (Basel, Switzerland), 26(6)","doi":"10.3390/molecules26061792","pmid":"33810198","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05558","title":"Soluble expression and purification of human β-defensin DEFB136 in Escherichia coli and identification of its bioactivity.","authors":"Liu, Haiyan; Diao, Hua; Hou, Jing; Yu, Heguo; Wen, Huiping","year":2021,"journal":"Protein expression and purification, 188, 105968","doi":"10.1016/j.pep.2021.105968","pmid":"34481960","tags":["defensins","antimicrobial-peptides"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Recombinant DEFB136 showed broad antimicrobial activity against E. coli, S. aureus, and C. albicans, plus high LPS-binding affinity with low cytotoxicity.","whyItMatters":"Characterizing new human defensins expands our understanding of innate immunity and could lead to new antimicrobial treatments.","specificNumbers":"Active against E. coli, S. aureus, C. albicans; high LPS-binding affinity; low hemolysis","methodology":"Protein expression in E. coli using IMPACT-TWIN system. Verified by mass spectrometry and circular dichroism. Tested antimicrobial activity, hemolysis, and LPS binding (octet assay).","limitations":"Only tested in lab conditions. Antimicrobial concentrations and in vivo effectiveness not established. Single expression system used."},{"rthcId":"RPEP-05559","title":"Structural basis of human ghrelin receptor signaling by ghrelin and the synthetic agonist ibutamoren.","authors":"Liu, Heng; Sun, Dapeng; Myasnikov, Alexander; Damian, Marjorie; Baneres, Jean-Louis; Sun, Ji; Zhang, Cheng","year":2021,"journal":"Nature communications, 12(1), 6410","doi":"10.1038/s41467-021-26735-5","pmid":"34737341","tags":["ghrelin","ghsr-receptor","peptide-drug-design"],"studyType":"mechanistic","evidenceStrength":"strong","keyFinding":"High-resolution cryo-EM structures revealed the molecular basis of ghrelin and ibutamoren binding to GHSR, identifying key activation motifs.","whyItMatters":"Knowing the exact shape of receptor-drug interactions speeds up the design of better, more selective drugs for appetite disorders and growth hormone conditions.","specificNumbers":"2 cryo-EM structures; GHSR-Gi complex; ghrelin requires Ser3 acylation; salt bridge + aromatic cluster activation motifs","methodology":"Cryo-electron microscopy of GHSR-Gi signaling complexes with ghrelin and ibutamoren. Combined with mutagenesis experiments to validate binding interactions.","limitations":"Structures captured in one signaling state (Gi-coupled). Receptor behavior in cell membranes may differ. Ibutamoren is investigational and not approved."},{"rthcId":"RPEP-05560","title":"Systematic Modeling, Prediction, and Comparison of Domain-Peptide Affinities: Does it Work Effectively With the Peptide QSAR Methodology?","authors":"Liu, Qian; Lin, Jing; Wen, Li; Wang, Shaozhou; Zhou, Peng; Mei, Li; Shang, Shuyong","year":2021,"journal":"Frontiers in genetics, 12, 800857","doi":"10.3389/fgene.2021.800857","pmid":"35096016","tags":["computational","qsar","drug-discovery"],"studyType":"computational","evidenceStrength":"moderate","keyFinding":"Traditional peptide QSAR (quantitative structure-activity relationship) methods can only predict domain-peptide binding affinities at a qualitative or semi-quantitative level — not with full quantitative precision. Using over 20,000 peptide segments interacting with SH3, PDZ, and 14-3-3 protein domains, the researchers found that the upper limit of prediction accuracy was R² = 0.7. Two key factors limit accuracy: the inherent flexibility of peptide structures makes them hard to model computationally, and the experimental affinity measurements themselves introduce significant noise.","whyItMatters":"Predicting how strongly peptides bind to their protein targets is crucial for designing peptide drugs. If computers could reliably predict binding affinities, drug development would be faster and cheaper. This study defines a realistic ceiling for one of the most common computational approaches, helping researchers understand when QSAR methods are useful and when they need alternative strategies.","specificNumbers":"R² = 0.7 upper limit for prediction accuracy · >20,000 peptide segments analyzed · 3 domain types (SH3, PDZ, 14-3-3) · 4 machine learning methods tested","methodology":"The team compiled over 20,000 short peptide segments known to interact with three types of protein domains (SH3, PDZ, 14-3-3). They represented each peptide using amino acid descriptors and applied four different machine learning methods to build predictive models. Models were rigorously validated using statistical cross-validation and external test sets.","limitations":"The binding affinity data came from an indirect measurement method (Boehringer light units from SPOT peptide synthesis), which introduces noise. The study focused on only three domain families and short linear peptide motifs, so results may not generalize to all peptide-protein interactions. The models did not account for three-dimensional structure or post-translational modifications."},{"rthcId":"RPEP-05561","title":"Peptide-based therapeutic cancer vaccine: Current trends in clinical application.","authors":"Liu, Wensi; Tang, Haichao; Li, Luanfeng; Wang, Xiangyi; Yu, Zhaojin; Li, Jianping","year":2021,"journal":"Cell proliferation, 54(5), e13025","doi":"10.1111/cpr.13025","pmid":"33754407","tags":["peptide-drug-design","immune-function"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Peptide cancer vaccines targeting TAAs or TSAs via CD8+/CD4+ epitopes have achieved clinical benefits. Adjuvants and nanomaterials improve immune responses. Combination with other therapies shows superior anti-cancer efficacy. Multiple candidates in advanced clinical development.","whyItMatters":"Unlike antibody immunotherapies (expensive, IV infusion), peptide vaccines are relatively cheap, easy to manufacture, and can be personalized. Understanding the current clinical landscape helps identify which approaches are most promising.","specificNumbers":"Targets: TAAs and TSAs; stimulates CD8+ and CD4+ T cells; adjuvants and nanomaterials reviewed","methodology":"Comprehensive narrative review of peptide-based therapeutic cancer vaccine development, covering target selection, epitope design/screening, adjuvant optimization, clinical trial results, and combination therapy strategies.","limitations":"Broad review — individual clinical trial details not deeply analyzed. Response rates for peptide vaccines alone remain modest. Tumor immune escape remains a challenge. Personalized neoantigen vaccines are logistically complex."},{"rthcId":"RPEP-05562","title":"An Ultrapotent and Selective Cyclic Peptide Inhibitor of Human β-Factor XIIa in a Cyclotide Scaffold.","authors":"Liu, Wenyu; de Veer, Simon J; Huang, Yen-Hua; Sengoku, Toru; Okada, Chikako; Ogata, Kazuhiro; Zdenek, Christina N; Fry, Bryan G; Swedberg, Joakim E; Passioura, Toby; Craik, David J; Suga, Hiroaki","year":2021,"journal":"Journal of the American Chemical Society, 143(44), 18481-18489","doi":"10.1021/jacs.1c07574","pmid":"34723512","tags":["peptide-drug-design","cyclotides"],"studyType":"in vitro","evidenceStrength":"moderate","keyFinding":"Engineered cyclotide containing a Factor XIIa inhibitor loop achieved ultrapotent and selective inhibition of human β-Factor XIIa while maintaining the cyclotide scaffold's proteolytic stability and cell permeability.","whyItMatters":"Factor XII drives pathological blood clotting (thrombosis) without being needed for normal wound healing — making it an ideal anticoagulant target. A cyclotide-based inhibitor could be more stable than existing peptide anticoagulants.","specificNumbers":">10^12 library; pM Ki for FXIIa; >1,000-fold selectivity; MCoTI-II scaffold; co-crystal structure","methodology":"Peptide engineering study. Factor XIIa inhibitor sequence grafted into cyclotide scaffold. Potency and selectivity profiling against coagulation factors. Stability and cell permeability assessment.","limitations":"In vitro potency and selectivity study. In vivo anti-thrombotic efficacy not tested. Cyclotide manufacturing at pharmaceutical scale is challenging. Immunogenicity of plant-derived scaffold in humans unknown."},{"rthcId":"RPEP-05563","title":"Facile Chemoselective Modification of Thioethers Generates Chiral Center-Induced Helical Peptides.","authors":"Liu, Yinghuan; Hu, Kuan; Yin, Feng; Li, Zigang","year":2021,"journal":"Methods in molecular biology (Clifton, N.J.), 2355, 301-322","doi":"10.1007/978-1-0716-1617-8_23","pmid":"34386967","tags":["peptide-drug-design","stapled-peptides"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Facile chemoselective thioether modification generates chiral center-containing stapled peptides, enabling direct study of how secondary conformation affects biophysical properties of peptide PPI inhibitors.","whyItMatters":"Understanding how peptide shape affects drug properties enables more rational design. Chiral stapled peptide pairs provide the first controlled way to study this — potentially doubling the design options for stapled peptide drugs.","specificNumbers":"R-configuration chiral center; thioether, sulfoxide, sulfonium systems; enhanced helicity, stability, cell penetration","methodology":"Synthetic chemistry study. Chemoselective modification of thioether linkages in stapled peptides. Chiral center generation. Conformational analysis. Biophysical property characterization.","limitations":"Chemistry methodology study. Biological activity comparisons of chiral peptide pairs not extensively characterized. Limited to thioether-stapled peptides."},{"rthcId":"RPEP-05564","title":"Integrated expression profiles of mRNA and miRNA in a gerbil model of fatty liver fibrosis treated with exenatide.","authors":"Liu, Yuehuan; Wu, Hongru; Wang, Zhiyuan; Wu, Jiusheng; Ying, Shibo; Huang, Minjie; Li, Youming","year":2021,"journal":"Clinics and research in hepatology and gastroenterology, 45(2), 101312","doi":"10.1016/j.clinre.2019.07.013","pmid":"33592427","tags":["glp-1-peptides","liver-health"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Exenatide reversed high-fat diet-induced liver fibrosis in gerbils. Integrated mRNA and miRNA expression profiling revealed specific gene and regulatory RNA networks modulated by exenatide, elucidating the molecular mechanisms of GLP-1RA hepatoprotection.","whyItMatters":"NAFLD affects 25% of the global population and has no approved pharmacotherapy. Understanding exactly how exenatide reverses liver fibrosis at the molecular level supports developing GLP-1 drugs specifically for liver disease.","specificNumbers":"8-week HFD; 4-week treatment; 2344 DEGs in model; 876 DEGs with exenatide; 18 miRNAs; key genes CYP3A, CYP4A11, ACAA1, ACOX2","methodology":"Animal study. Gerbil high-fat diet (8 weeks) fatty liver/fibrosis model. Exenatide treatment. Integrated mRNA and miRNA expression profiling. Bioinformatics analysis of regulatory networks.","limitations":"Gerbil model — may not fully replicate human NAFLD. Transcriptomic data doesn't confirm protein-level changes. Short-term high-fat diet model may differ from chronic human liver disease. Specific gene targets need functional validation."},{"rthcId":"RPEP-05565","title":"Agonistic analog of growth hormone-releasing hormone promotes neurofunctional recovery and neural regeneration in ischemic stroke.","authors":"Liu, Yueyang; Yang, Jingyu; Che, Xiaohang; Huang, Jianhua; Zhang, Xianyang; Fu, Xiaoxiao; Cai, Jialing; Yao, Yang; Zhang, Haotian; Cai, Ruiping; Su, Xiaomin; Xu, Qian; Ren, Fu; Cai, Renzhi; Schally, Andrew V; Zhou, Ming-Sheng","year":2021,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 118(47)","doi":"10.1073/pnas.2109600118","pmid":"34782465","tags":["ghrh-analogs","neuroprotection"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"MR-409 (5-10 μg/mouse/day SC) reduced mortality, ischemic damage, and hippocampal atrophy in tMCAO stroke mice. Enhanced endogenous neurogenesis and neuroplasticity. Protected neural stem cells from oxygen-glucose deprivation. Mechanism: AKT/CREB and BDNF/TrkB activation.","whyItMatters":"Stroke is the second leading cause of death and leading cause of disability worldwide. No drug currently promotes brain repair after stroke. A GHRH agonist that both protects neurons and generates new ones could be transformative.","specificNumbers":"5 or 10 μg/mouse/day s.c.; reduced mortality and ischemic insult; pathways: AKT/CREB, BDNF/TrkB; tMCAO model","methodology":"Animal study. Transient middle cerebral artery occlusion (tMCAO) stroke model in mice. MR-409 subcutaneous injection (5 or 10 μg/mouse/day). Mortality, infarct size, hippocampal volume, neurogenesis, and neurological function assessed. Neural stem cell in vitro studies. AKT/CREB and BDNF/TrkB pathway analysis.","limitations":"Mouse stroke model — human stroke is more complex. Long-term treatment started after stroke onset. Translation of neurogenesis findings to humans uncertain. Specific contribution of growth hormone release vs direct neuroprotection not fully separated."},{"rthcId":"RPEP-05566","title":"Paeoniflorin inhibits the macrophage-related rosacea-like inflammatory reaction through the suppressor of cytokine signaling 3-apoptosis signal-regulating kinase 1-p38 pathway.","authors":"Liu, Zijing; Zhang, Jiawen; Jiang, Peiyu; Yin, Zhi; Liu, Yunyi; Liu, Yixuan; Wang, Xiaoyan; Hu, Liang; Xu, Yang; Liu, Wentao","year":2021,"journal":"Medicine, 100(3), e23986","doi":"10.1097/MD.0000000000023986","pmid":"33545988","tags":["cathelicidins","skin-health","inflammation"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Paeoniflorin promoted SOCS3 expression and inhibited LPS-induced TLR2 and LL-37 expression through SOCS3-ASK1-p38 cascade in macrophages. Rosacea lesions showed increased LL-37 and CD68+ macrophage infiltration. SOCS3 siRNA reversed PF's effects, confirming the mechanism.","whyItMatters":"LL-37 overexpression is a recognized driver of rosacea inflammation, but current treatments don't specifically target this pathway. PF offers a mechanism-based approach to treating the root cause of rosacea rather than just managing symptoms.","specificNumbers":"Pathway: SOCS3-ASK1-p38; reduced TLR2 and LL37; CD68+ macrophage infiltration in lesions; siRNA confirmation","methodology":"Clinical tissue analysis + in vitro mechanistic study. Immunohistochemistry of granulomatous rosacea lesions vs peripheral tissue. RAW 264.7 macrophage cell model with LPS stimulation. PF treatment effects on SOCS3, ASK1-p38, TLR2, and LL-37. SOCS3 siRNA knockdown for mechanism confirmation.","limitations":"In vitro macrophage model with LPS stimulation — rosacea triggers are more complex. No in vivo rosacea model tested. PF bioavailability for topical skin application unknown. Clinical trial data needed."},{"rthcId":"RPEP-05567","title":"LEAP-2: An Emerging Endogenous Ghrelin Receptor Antagonist in the Pathophysiology of Obesity.","authors":"Lu, Xuehan; Huang, Lili; Huang, Zhengxiang; Feng, Dandan; Clark, Richard J; Chen, Chen","year":2021,"journal":"Frontiers in endocrinology, 12, 717544","doi":"10.3389/fendo.2021.717544","pmid":"34512549","tags":["ghrelin","ghsr-receptor","antimicrobial-peptides","obesity-metabolism"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"LEAP-2 acts as both competitive ghrelin antagonist and inverse agonist of constitutive GHS-R1a activity. LEAP-2 increases with feeding/obesity, decreases with fasting/weight loss — inverse to ghrelin. LEAP-2/ghrelin molar ratio fluctuates with energy status and modulates food intake.","whyItMatters":"The body already has a natural hunger suppressor that counters ghrelin. Understanding and enhancing LEAP-2 signaling could provide a physiological, targeted approach to obesity treatment — working with the body's own appetite regulation rather than against it.","specificNumbers":"LEAP-2: competitive antagonist + inverse agonist of GHS-R1a; increases with feeding/obesity; decreases with fasting/weight loss","methodology":"Narrative review of LEAP-2 biology, GHS-R1a pharmacology, circulating LEAP-2/ghrelin dynamics, and metabolic effects. Discussion of LEAP-2 as therapeutic target for obesity.","limitations":"Review article. LEAP-2 therapeutic applications are conceptual — no clinical trials yet. LEAP-2's effects on metabolic parameters beyond appetite need further study. The optimal LEAP-2/ghrelin ratio for weight management is unknown."},{"rthcId":"RPEP-05568","title":"Protease-Resistant Peptides for Targeting and Intracellular Delivery of Therapeutics.","authors":"Lucana, Maria C; Arruga, Yolanda; Petrachi, Emilia; Roig, Albert; Lucchi, Roberta; Oller-Salvia, Benjamí","year":2021,"journal":"Pharmaceutics, 13(12)","doi":"10.3390/pharmaceutics13122065","pmid":"34959346","tags":["peptide-drug-design","cell-penetrating-peptides"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Comprehensive review of strategies to enhance peptide proteolytic resistance for targeting and intracellular delivery: D-amino acids, cyclization, PEGylation, unnatural amino acids, backbone modifications, and hybrid approaches.","whyItMatters":"Proteolytic degradation is the single biggest barrier to peptide therapeutics. A comprehensive understanding of stabilization strategies enables rational design of peptide drugs that survive in the body.","specificNumbers":"Strategies: N/C-cap, cyclization, backbone mod, D-amino acids, conjugation; best for brain delivery: retro-enantio","methodology":"Narrative review of chemical modification strategies for protease-resistant peptide design in drug delivery applications.","limitations":"Review article. Different strategies suit different peptide applications. Some modifications may reduce biological activity. Manufacturing complexity varies widely."},{"rthcId":"RPEP-05569","title":"Sodium-glucose cotransporter-2 inhibitors and the risk of gout: A Danish population based cohort study and symmetry analysis.","authors":"Lund, Lars Christian; Højlund, Mikkel; Henriksen, Daniel Pilsgaard; Hallas, Jesper; Kristensen, Kasper Bruun","year":2021,"journal":"Pharmacoepidemiology and drug safety, 30(10), 1391-1395","doi":"10.1002/pds.5252","pmid":"33881179","tags":["glp-1-peptides","sglt2-inhibitors","metabolic-health"],"studyType":"observational","evidenceStrength":"strong","keyFinding":"SGLT2 inhibitors associated with reduced gout risk compared to other antidiabetic medications in a Danish population-based cohort. GLP-1 peptides also showed potential gout risk reduction.","whyItMatters":"Gout affects millions of diabetes patients and causes debilitating pain. Drugs that control blood sugar AND reduce gout risk provide dual benefits, informing medication choice for patients with both conditions.","specificNumbers":"N=11,047 pairs; 42,201 person-years; HR 0.58 (0.44-0.75); IRD -3.0; SR 0.63 (0.47-0.84); 4.1 vs 7.0/1000 PY","methodology":"Danish population-based cohort study. SGLT2 inhibitor and GLP-1 RA use compared to other antidiabetic medications for gout incidence.","limitations":"Observational population study — cannot prove causation. Confounding by indication possible. GLP-1 gout evidence less robust than SGLT2i. Danish population may not generalize to other ethnicities."},{"rthcId":"RPEP-05570","title":"A novel anionic cathelicidin lacking direct antimicrobial activity but with potent anti-inflammatory and wound healing activities from the salamander Tylototriton kweichowensis.","authors":"Luo, Xuanjin; Ouyang, Jianhong; Wang, Yan; Zhang, Minghui; Fu, Lei; Xiao, Ning; Gao, Lianghui; Zhang, Peng; Zhou, Jiang; Wang, Yipeng","year":2021,"journal":"Biochimie, 191, 37-50","doi":"10.1016/j.biochi.2021.08.007","pmid":"34438004","tags":["cathelicidins","wound-healing","antimicrobial-peptides"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"TK-CATH: first anionic cathelicidin (net charge -3). No direct antimicrobial activity. Potent anti-inflammatory (inhibited LPS-induced cytokines via MAPK). Promoted wound healing: cytokines, chemokines, growth factors, keratinocyte motility/proliferation, and accelerated full-thickness wound repair in mice.","whyItMatters":"Discovering a cathelicidin that heals wounds without killing bacteria changes how we think about antimicrobial peptides. It suggests the cathelicidin family evolved specialized members for tissue repair, not just pathogen defense — with direct therapeutic implications.","specificNumbers":"Net charge -3; inhibits MAPK signaling; promotes keratinocyte motility/proliferation; accelerated full-thickness wound healing in mice","methodology":"Discovery and characterization study. TK-CATH identified from T. kweichowensis salamander skin. Anti-inflammatory testing in amphibian leukocytes and mouse macrophages. MAPK pathway analysis. Wound healing: keratinocyte assays and mouse full-thickness wound model. Free radical scavenging and cytotoxicity assessment.","limitations":"Salamander peptide — may not directly translate to human therapy. TK-CATH would need modification for human therapeutic use. Mouse wound model is relatively simple. Mechanism of wound healing beyond cytokine induction not fully detailed."},{"rthcId":"RPEP-05571","title":"Physical methods for enhancing drug absorption from the gastrointestinal tract.","authors":"Luo, Zhi; Paunović, Nevena; Leroux, Jean-Christophe","year":2021,"journal":"Advanced drug delivery reviews, 175, 113814","doi":"10.1016/j.addr.2021.05.024","pmid":"34052229","tags":["peptide-drug-design","oral-peptide-delivery"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Physical enhancement methods for oral peptide absorption include ultrasound-mediated permeabilization, intestinal microneedle capsules, iontophoresis (electric field-driven transport), and mechanical mucosal disruption devices.","whyItMatters":"Oral peptide delivery could transform patient experience for millions on injectable drugs. Physical methods offer alternatives when chemical modifications aren't sufficient.","specificNumbers":"Methods: magnetic, acoustic, mechanical forces; 40+ years of chemical approach research; oral peptide bioavailability remains very low","methodology":"Narrative review of physical methods for enhancing gastrointestinal drug absorption, focusing on peptide and macromolecule delivery applications.","limitations":"Review of mostly early-stage technologies. Clinical safety and patient acceptance of ingestible devices unknown. Manufacturing complexity and cost may limit access."},{"rthcId":"RPEP-05572","title":"Improving Membrane Activity and Cargo Delivery Efficacy of a Cell-Penetrating Peptide by Loading with Carboranes.","authors":"Lützenburg, Tamara; Burdina, Nele; Scholz, Matthias S; Neundorf, Ines","year":2021,"journal":"Pharmaceutics, 13(12)","doi":"10.3390/pharmaceutics13122075","pmid":"34959356","tags":["cell-penetrating-peptides","peptide-drug-design"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Systematic CPP modifications improved membrane interaction activity and cargo delivery efficacy for enhanced intracellular delivery of therapeutic molecules.","whyItMatters":"Better CPPs mean less drug wasted outside cells and more reaching intracellular targets. Even modest improvements in delivery efficiency can dramatically reduce required doses and side effects.","specificNumbers":"1+ carborane clusters per CPP; altered secondary structure; improved nucleic acid delivery","methodology":"In vitro study. CPP sequence modifications. Membrane activity characterization. Cargo delivery efficiency measurement. Structure-activity relationship analysis.","limitations":"In vitro study. Specific cargo types tested limited. In vivo performance not assessed. Improvements may be peptide-specific."},{"rthcId":"RPEP-05573","title":"GLP-1 receptor agonists (GLP-1RAs): cardiovascular actions and therapeutic potential.","authors":"Ma, Xiaoxuan; Liu, Zhenghong; Ilyas, Iqra; Little, Peter J; Kamato, Danielle; Sahebka, Amirhossein; Chen, Zhengfang; Luo, Sihui; Zheng, Xueying; Weng, Jianping; Xu, Suowen","year":2021,"journal":"International journal of biological sciences, 17(8), 2050-2068","doi":"10.7150/ijbs.59965","pmid":"34131405","tags":["glp-1-peptides","cardiovascular-health"],"studyType":"review","evidenceStrength":"strong","keyFinding":"GLP-1RAs provide cardiovascular benefits including atherosclerosis reduction, blood pressure lowering, heart failure protection, and anti-inflammatory effects. These benefits are partly independent of glucose control and weight loss.","whyItMatters":"CVD is the leading killer of diabetes patients. Recognizing GLP-1 drugs as cardiovascular protectors — not just glucose-lowering agents — could shift prescribing patterns and save lives.","specificNumbers":"GLP-1R on monocytes, smooth muscle, endothelial cells, cardiomyocytes; CVOTs confirm reduced CVD; lower lipids, BP, atherosclerosis","methodology":"Narrative review of GLP-1RA cardiovascular actions covering preclinical mechanisms, clinical trial evidence, and therapeutic implications for CVD management.","limitations":"Review article. Not all GLP-1RAs show identical cardiovascular benefit. Mechanisms partially overlap with weight loss effects. Non-diabetic CVD population data limited."},{"rthcId":"RPEP-05574","title":"tLyP-1 Peptide Functionalized Human H Chain Ferritin for Targeted Delivery of Paclitaxel.","authors":"Ma, Yuanmeng; Li, Ruike; Dong, Yixin; You, Chaoqun; Huang, Shenlin; Li, Xun; Wang, Fei; Zhang, Yu","year":2021,"journal":"International journal of nanomedicine, 16, 789-802","doi":"10.2147/IJN.S289005","pmid":"33568906","tags":["peptide-drug-design","tumor-targeting-peptides"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"The tLyP-1-functionalized ferritin nanoparticles (tLyP-1-HFtn-PTX) showed enhanced intracellular delivery and superior cytotoxicity against both SMMC-7721 liver cancer and MDA-MB-231 breast cancer cells compared to unmodified ferritin-PTX. The peptide-decorated nanoparticles also demonstrated better anti-invasion ability and deeper penetration into tumor spheroids.\n\nIn live mice with breast cancer xenografts, tLyP-1-HFtn-PTX selectively accumulated at tumor sites and displayed higher therapeutic efficacy with lower systemic toxicity. Notably, the tLyP-1 peptide functioned effectively at the N-terminal of ferritin, contrary to the previous assumption that it only works at the C-terminus.","whyItMatters":"Targeted drug delivery is one of the biggest challenges in cancer treatment. This study demonstrates that a relatively simple modification — attaching a tumor-homing peptide to a naturally occurring protein cage — can significantly improve chemotherapy targeting. If this approach translates to humans, it could mean more effective cancer treatment with fewer of the debilitating side effects that make chemotherapy so difficult to tolerate.","specificNumbers":"tLyP-1 at N-terminal of HFtn; PTX loaded via pH disassembly/assembly; enhanced uptake, cytotoxicity, anti-invasion; lower systemic toxicity","methodology":"Researchers fused the tLyP-1 peptide to the N-terminal of human H chain ferritin and loaded paclitaxel into the nanocage using a pH-based disassembly/reassembly method. They tested cellular uptake using confocal microscopy and flow cytometry, measured cytotoxicity with MTT assays on breast and liver cancer cells, and assessed anti-migration effects with wound healing assays. Tumor penetration was evaluated using 3D tumor spheroids. In vivo efficacy was tested in BALB/c nude mice bearing MDA-MB-231 breast cancer xenografts.","limitations":"Only one tumor model was tested in vivo (breast cancer xenograft in nude mice), which does not reflect the full heterogeneity of human cancers. Immunocompromised mice lack a functioning immune system, so immune-related effects are unknown. Long-term safety data is not available. Manufacturing peptide-decorated ferritin nanoparticles at pharmaceutical scale presents significant technical challenges. The study did not test the approach in combination with standard-of-care regimens."},{"rthcId":"RPEP-05575","title":"Enhanced Anticancer Efficacy of Dual Drug-Loaded Self-Assembled Nanostructured Lipid Carriers Mediated by pH-Responsive Folic Acid and Human-Derived Cell Penetrating Peptide dNP2.","authors":"Ma, Zhe; Pi, Jiaxin; Zhang, Ying; Qin, Huan; Zhang, Bing; Li, Nan; Li, Zheng; Liu, Zhidong","year":2021,"journal":"Pharmaceutics, 13(5)","doi":"10.3390/pharmaceutics13050600","pmid":"33921919","tags":["cell-penetrating-peptides","peptide-drug-design"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Dual cFA/dNP2 modification gave nanoparticles better tumor targeting, cell penetration, and anticancer efficacy than single-ligand systems.","whyItMatters":"Getting drugs inside tumor cells is a major challenge. This dual-targeting approach solves two problems at once: finding tumors and penetrating them.","specificNumbers":"Drugs: GA + PTX; dNP2 sequence: CKIKKVKKKGRKKIKKVKKKGRK; cFA cleaves at tumor pH; superior to single-ligand NLCs","methodology":"In vitro cellular uptake and cytotoxicity with 4T1 cells. In vivo biodistribution and anticancer efficacy testing.","limitations":"Single mouse tumor model. Complex manufacturing process. Long-term safety of dual-modified nanoparticles unknown."},{"rthcId":"RPEP-05576","title":"Utilizing Developmentally Essential Secreted Peptides Such as Thymosin Beta-4 to Remind the Adult Organs of Their Embryonic State-New Directions in Anti-Aging Regenerative Therapies.","authors":"Maar, Klaudia; Hetenyi, Roland; Maar, Szabolcs; Faskerti, Gabor; Hanna, Daniel; Lippai, Balint; Takatsy, Aniko; Bock-Marquette, Ildiko","year":2021,"journal":"Cells, 10(6)","doi":"10.3390/cells10061343","pmid":"34071596","tags":["thymosin-beta-4","regenerative-medicine","cardiac-peptides"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"TB4, a developmentally essential 43aa secreted peptide, demonstrates multiple cardiac regenerative capabilities via systemic administration in adult organisms. The concept proposes using developmental peptides to reactivate embryonic regenerative programs in aging organs.","whyItMatters":"Current anti-aging approaches mostly slow damage. Using developmental peptides to actively reactivate regeneration is a fundamentally different strategy — potentially restoring organ function rather than just preventing decline.","specificNumbers":"Tβ4: 43 amino acids; systemic administration; cardiac regeneration; embryonic developmental peptide","methodology":"Perspective/review article. Discusses TB4 cardiac regeneration evidence, proposes a conceptual framework for using developmentally essential peptides in anti-aging regenerative medicine.","limitations":"Perspective/concept paper — many claims are aspirational. TB4 cardiac benefits proven in animals but not in clinical trials. The assumption that other developmental peptides exist and can be similarly deployed is unproven. Anti-aging claims are speculative."},{"rthcId":"RPEP-05577","title":"Formulation strategies to improve the efficacy of intestinal permeation enhancers.","authors":"Maher, Sam; Brayden, David J","year":2021,"journal":"Advanced drug delivery reviews, 177, 113925","doi":"10.1016/j.addr.2021.113925","pmid":"34418495","tags":["oral-peptide-delivery","glp-1-peptides","somatostatin-analogs"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Formulation strategies including enteric coatings, nanoparticle co-encapsulation, mucoadhesive formulations, and timed-release systems optimize intestinal permeation enhancer efficacy for oral peptide delivery.","whyItMatters":"Oral semaglutide (Rybelsus) proved oral peptides are possible, but its bioavailability is still low (~1%). Better formulation strategies could dramatically improve oral peptide drug absorption and efficacy.","specificNumbers":"~1% BA; FDA approvals: oral semaglutide, oral octreotide; challenges: dilution, transit, luminal interference","methodology":"Narrative review of formulation approaches for optimizing IPE-peptide co-delivery and overcoming GI barriers.","limitations":"Review article. Most strategies preclinical. No single formulation approach solves all challenges. Patient-to-patient variability in GI conditions complicates universal formulation design."},{"rthcId":"RPEP-05578","title":"RGD peptide-mediated liposomal curcumin targeted delivery to breast cancer cells.","authors":"Mahmoudi, Reza; Ashraf Mirahmadi-Babaheidri, Seyedeh; Delaviz, Hamdollah; Fouani, Mohamad Hassan; Alipour, Mohsen; Jafari Barmak, Mehrzad; Christiansen, Gunna; Bardania, Hassan","year":2021,"journal":"Journal of biomaterials applications, 35(7), 743-753","doi":"10.1177/0885328220949367","pmid":"32807016","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"RGD peptide-modified liposomes loaded with curcumin (RGD-Lip-Cur) demonstrated significantly greater cytotoxicity against MCF-7 breast cancer cells compared to both unmodified curcumin liposomes and free curcumin.\n\nAt concentrations of 32, 16, and 4 μg/ml, the RGD-targeted version was significantly more toxic to cancer cells (p<0.05 vs plain liposomes, p<0.01 vs free curcumin). The apoptosis assay showed RGD-Lip-Cur induced 39.6% early apoptosis and 40.2% late apoptosis in cancer cells. The formulation also activated caspase 3/7 (cell death enzymes) significantly more than controls. Importantly, RGD-Lip-Cur showed no significant toxicity to normal cells.","whyItMatters":"One of the biggest challenges in cancer treatment is getting drugs to cancer cells without harming healthy tissue. RGD peptides specifically recognize integrins overexpressed on tumor cells, acting as a homing device. This study demonstrates that peptide-guided delivery can dramatically improve curcumin's cancer-killing ability, a proof of concept for using peptides to target natural compounds directly to tumors.","specificNumbers":"","methodology":"Researchers encapsulated curcumin into liposomes (70-100 nm spherical nanoparticles) and attached RGD peptides to their surface. They characterized the particles using transmission electron microscopy, then tested cytotoxicity against MCF-7 breast cancer cells using three methods: MTT assay (cell viability), flow cytometry (apoptosis measurement), and caspase 3/7 assay (programmed cell death activation).","limitations":"This was an in vitro study using a single breast cancer cell line (MCF-7), so results may not translate to tumors in living organisms. No animal studies or human trials were conducted. The study did not test against multiple cancer cell lines or assess how the liposomes would behave in the bloodstream. Long-term stability of the RGD-liposome formulation was not evaluated."},{"rthcId":"RPEP-05579","title":"Treatments for NAFLD: State of Art.","authors":"Mantovani, Alessandro; Dalbeni, Andrea","year":2021,"journal":"International journal of molecular sciences, 22(5)","doi":"10.3390/ijms22052350","pmid":"33652942","tags":["glp-1-peptides","liver-health","metabolic-health"],"studyType":"review","evidenceStrength":"strong","keyFinding":"No approved NAFLD-specific pharmacotherapy. Current approaches: lifestyle modification, pioglitazone, vitamin E. Emerging: GLP-1RAs showing promise for liver fat reduction and inflammation. NAFLD affects ~30% of adults, up to 70% of T2DM patients.","whyItMatters":"NAFLD is becoming the leading cause of liver transplantation. GLP-1 drugs that address both diabetes and fatty liver could treat the root cause for millions of patients with overlapping conditions.","specificNumbers":"30% prevalence; 70% in T2DM; candidates: pioglitazone, GLP-1RAs, SGLT2i, vitamin E, statins, FXR agonists","methodology":"Narrative review of NAFLD treatment landscape covering epidemiology, pathogenesis, current therapies, and emerging pharmacological approaches.","limitations":"Review article. Most emerging drugs in early-to-mid clinical development. Long-term outcomes data limited. NAFLD heterogeneity makes one-size-fits-all treatment difficult."},{"rthcId":"RPEP-05580","title":"The evolving story of incretins (GIP and GLP-1) in metabolic and cardiovascular disease: A pathophysiological update.","authors":"Nauck, Michael A; Quast, Daniel R; Wefers, Jakob; Pfeiffer, Andreas F H","year":2021,"journal":"Diabetes, obesity & metabolism, 23 Suppl 3, 5-29","doi":"10.1111/dom.14496","pmid":"34310013","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GIP and GLP-1 have additive effects on insulin secretion, but they differ in key ways: GLP-1 suppresses glucagon and slows stomach emptying while GIP increases glucagon secretion and promotes fat storage in adipose tissue. In type 2 diabetes, GIP's ability to stimulate insulin is severely impaired for largely unknown reasons, while GLP-1's effect is only slightly reduced.\n\nBeyond glucose control, GLP-1 at pharmacological doses reduces appetite and body weight. GIP shows similar effects in animal studies but not yet convincingly in humans. Both hormones show beneficial effects on cardiovascular disease and neurodegenerative CNS disorders. The superior efficacy of the GIP/GLP-1 co-agonist tirzepatide over selective GLP-1 agonists has fundamentally changed the perception of GIP from a therapeutically useless hormone to a key drug target.","whyItMatters":"Understanding exactly how GIP and GLP-1 work — and how they differ — is essential for designing better diabetes and obesity drugs. This review explains why combining GIP and GLP-1 receptor activation produces better results than either alone, providing the scientific foundation for why tirzepatide and similar dual agonists represent a therapeutic leap. It also highlights that these hormones affect far more than blood sugar, potentially opening treatment avenues for heart disease and neurodegeneration.","specificNumbers":"","methodology":"This is a comprehensive pathophysiological review and update published as a supplement article. The authors synthesize decades of research on incretin physiology, pathophysiology in type 2 diabetes, and the expanding understanding of GIP and GLP-1 biology across multiple organ systems including pancreas, gut, adipose tissue, bone, cardiovascular system, and brain.","limitations":"As a review, this synthesizes existing research rather than presenting new data. Some of the proposed mechanisms — particularly GIP's role in weight regulation in humans — remain unresolved, with animal and human data pointing in different directions. The review was published before some later clinical trial results were available. The reasons why GIP loses its insulinotropic effect in type 2 diabetes remain largely unknown, limiting mechanistic understanding."},{"rthcId":"RPEP-05581","title":"The GhsrQ343X allele favors the storage of fat by acting on nutrient partitioning.","authors":"Marion, Candice; Zizzari, Philippe; Denis, Raphaël G P; Hassouna, Rim; Chebani, Yacine; Leste-Lasserre, Thierry; Doat, Hélène; Le Pen, Gwenaëlle; Cota, Daniela; Noble, Florence; Luquet, Serge; Pantel, Jacques","year":2021,"journal":"The Journal of endocrinology, 251(3), 181–194","doi":"10.1530/JOE-20-0576","pmid":"34582357","tags":["ghrelin","ghsr-receptor","obesity-metabolism"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"GhsrQ343X allele alters nutrient partitioning to favor fat storage through constitutive GHSR activity, independent of ghrelin-mediated effects. Demonstrates that GHSR baseline signaling independently regulates metabolic programming.","whyItMatters":"Understanding why some people store fat more easily despite similar diets could explain individual obesity susceptibility. GHSR constitutive activity — without ghrelin — may be an underappreciated driver of body composition.","specificNumbers":"GhsrQ343X mutation; preferential CHO oxidation; no change in intake/expenditure/activity; increased LEAP2:ghrelin ratio; increased hypothalamic Ghsr","methodology":"Genetic and metabolic study. GhsrQ343X allele characterization. Nutrient partitioning analysis. Fat vs lean mass composition. Constitutive GHSR activity assessment independent of ghrelin.","limitations":"Genetic variant study — population frequency and clinical impact need characterization. Mechanistic details of nutrient partitioning not fully elucidated. Translation from model to human phenotype needs confirmation."},{"rthcId":"RPEP-05582","title":"Physiological and Pharmacological Roles of PTH and PTHrP in Bone Using Their Shared Receptor, PTH1R.","authors":"Martin, T John; Sims, Natalie A; Seeman, Ego","year":2021,"journal":"Endocrine reviews, 42(4), 383-406","doi":"10.1210/endrev/bnab005","pmid":"33564837","tags":["parathyroid-hormone","bone-health"],"studyType":"review","evidenceStrength":"strong","keyFinding":"PTH and PTHrP share amino-terminal domain identity and PTH1R receptor activation but have distinct physiological and pharmacological roles in bone. Intermittent PTH builds bone (anabolic) while continuous PTH breaks it down (catabolic). Genetic models clarify mechanism distinctions.","whyItMatters":"Osteoporosis affects 200+ million people. Understanding how related peptide hormones build vs break bone enables design of better anabolic bone drugs — exemplified by teriparatide (PTH fragment) and abaloparatide (PTHrP-based).","specificNumbers":"PTH1R shared receptor; cAMP-PKA pathway; teriparatide (PTH) and abaloparatide (PTHrP); intermittent = anabolic, continuous = catabolic","methodology":"Narrative review of PTH and PTHrP bone biology using genetic model data to distinguish their physiological and pharmacological roles through PTH1R signaling.","limitations":"Review based heavily on genetic models that may not fully replicate human bone physiology. PTH1R signaling complexity not fully resolved. Clinical implications of some genetic findings unclear."},{"rthcId":"RPEP-05583","title":"Mitochondrial humanin peptide acts as a cytoprotective factor in granulosa cell survival.","authors":"Marvaldi, Carolina; Martin, Daniel; Conte, Julia G; Gottardo, María Florencia; Pidre, Matías L; Imsen, Mercedes; Irizarri, Martin; Manuel, Sharron L; Duncan, Francesca E; Romanowski, Víctor; Seilicovich, Adriana; Jaita, Gabriela","year":2021,"journal":"Reproduction (Cambridge, England), 161(5), 581-591","doi":"10.1530/REP-20-0197","pmid":"33764899","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05584","title":"Refractoriness to drugs in migraine may be the result of developing anti-drug antibodies.","authors":"Maselis, K; Žekevičiūtė, R; Vaitkus, A","year":2021,"journal":"Medical hypotheses, 146, 110459","doi":"10.1016/j.mehy.2020.110459","pmid":"33360448","tags":["neuropeptides","cgrp"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Refractory migraine may result from anti-drug antibody development against biologic treatments including anti-CGRP monoclonal antibodies. Multiple mechanisms of pharmacological refractoriness discussed including immunogenicity, receptor changes, and metabolic tolerance.","whyItMatters":"Millions of migraine patients fail multiple treatments. Understanding that some failures are due to anti-drug antibodies — rather than the disease being truly untreatable — opens new management strategies like drug switching or immunomodulation.","specificNumbers":"Antibody types: IgG, IgA; mechanism: hapten-carrier complexes; drug tolerance vs. drug allergy distinction","methodology":"Narrative review discussing mechanisms of pharmacological refractoriness in migraine, with focus on anti-drug antibody development, receptor desensitization, and metabolic factors.","limitations":"Review/perspective article. Anti-drug antibody rates for specific anti-CGRP mAbs not fully quantified. Not all migraine refractoriness is antibody-mediated. Testing for anti-drug antibodies is not routine in migraine clinics."},{"rthcId":"RPEP-05585","title":"Effects of GLP-1 and Its Analogs on Gastric Physiology in Diabetes Mellitus and Obesity.","authors":"Maselli, Daniel B; Camilleri, Michael","year":2021,"journal":"Advances in experimental medicine and biology, 1307, 171-192","doi":"10.1007/5584_2020_496","pmid":"32077010","tags":[],"studyType":"review","evidenceStrength":"review","keyFinding":"GLP-1 agonists and analogs work in part by slowing gastric emptying — food stays in the stomach longer, which reduces post-meal blood sugar spikes. However, this gastric slowing effect diminishes with long-acting preparations and with long-term use of short-acting preparations through tachyphylaxis (the body adapts to continuous exposure).\n\nKey findings from the reviewed literature: endogenous GLP-1 has a half-life of only 2-3 minutes (destroyed by DPP-IV enzyme). GLP-1 infusion slows gastric emptying and increases gastric volumes. Dual GLP-1/GIP agonists (like tirzepatide) do not appear to retard gastric emptying based on reports at the time of review. The chapter also notes that most studies used the acetaminophen absorption test, which primarily measures liquid gastric emptying in the first hour, while scintigraphy provides more valid measurements.","whyItMatters":"Understanding that GLP-1 drugs work partly through the stomach — not just through insulin — explains several clinical observations: why patients on GLP-1 drugs feel full quickly, why nausea is the most common side effect, why the gastric slowing effect fades with long-acting drugs, and why short-acting GLP-1 agonists are better at controlling post-meal glucose spikes. This gastric mechanism is also relevant to the gastroparesis-like symptoms some patients experience.","specificNumbers":"Endogenous GLP-1 half-life: 2-3 minutes · Destroyed by DPP-IV · Slows gastric emptying · Increases fasting and postprandial gastric volumes · Tachyphylaxis with long-acting or chronic use · GLP-1/GIP dual agonists don't retard gastric emptying","methodology":"Book chapter reviewing published literature on GLP-1's effects on gastric motor function. Evaluates different measurement methods (scintigraphy, acetaminophen absorption test) and synthesizes findings across GLP-1 agonist and analog studies in diabetes and obesity.","limitations":"Published in 2021, this review predates much of the clinical experience with tirzepatide and high-dose semaglutide. The finding that dual GLP-1/GIP agonists don't retard gastric emptying was based on limited early reports and may have been updated by subsequent data. The review notes methodological inconsistencies in how gastric emptying has been measured across studies."},{"rthcId":"RPEP-05586","title":"Glucagon-like peptide-1 receptor agonists as neuroprotective agents for ischemic stroke: a systematic scoping review.","authors":"Maskery, Mark P; Holscher, Christian; Jones, Stephanie P; Price, Christopher I; Strain, W David; Watkins, Caroline L; Werring, David J; Emsley, Hedley Ca","year":2021,"journal":"Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 41(1), 14-30","doi":"10.1177/0271678X20952011","pmid":"32954901","tags":["glp-1-peptides","neuroprotection"],"studyType":"systematic review","evidenceStrength":"strong","keyFinding":"GLP-1RAs demonstrate pre-clinical neuroprotective efficacy in multiple ischemic stroke models: reducing infarct size, inflammation, and improving functional outcomes. Established safety and availability position them as practical stroke neuroprotectant candidates.","whyItMatters":"Stroke neuroprotection has been called the \"graveyard of drug development\" with dozens of failed clinical trials. GLP-1 drugs' unique advantage — already proven safe in millions of patients — removes the biggest barrier to clinical testing.","specificNumbers":"35 preclinical studies; 24h treatment window; reduced infarct, apoptosis, oxidative stress, inflammation; increased neurogenesis, angiogenesis; semaglutide + dulaglutide reduced stroke in CVOTs","methodology":"Narrative review of preclinical and early clinical evidence for GLP-1RA neuroprotection in ischemic stroke. Covers multiple GLP-1 drugs across various stroke models.","limitations":"Most evidence preclinical. Clinical stroke trial results limited. Optimal dose, timing, and GLP-1 drug selection for stroke not established. Animal stroke models may not predict human efficacy."},{"rthcId":"RPEP-05587","title":"Efficacy of calcitonin gene-related peptide (CGRP) receptor blockers in reducing the number of monthly migraine headache days (MHDs): A network meta-analysis of randomized controlled trials.","authors":"Masoud, Ahmed Taher; Hasan, Mohammed Tarek; Sayed, Ahmed; Edward, Harvey Nabil; Amer, Ahmed Mohamed; Naga, Abdelrahman Elshahat; Elfil, Mohamed; Alghamdi, Badrah S; Perveen, Asma; Ashraf, Ghulam Md; Bahbah, Eshak I","year":2021,"journal":"Journal of the neurological sciences, 427, 117505","doi":"10.1016/j.jns.2021.117505","pmid":"34082147","tags":["cgrp","neuropeptides"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"At 6 weeks: fremanezumab 900mg most effective (SMD=-0.55). At 8 weeks: erenumab 140mg most effective (SMD=-0.51). At 12 weeks: erenumab 140mg most effective (SMD=-0.48). For chronic migraine: fremanezumab 900mg best at 6 weeks, erenumab 140mg best at 8 and 12 weeks.","whyItMatters":"Choosing between four similar drugs is difficult without comparative data. This NMA provides evidence-based rankings by timepoint and migraine type, enabling more informed prescribing decisions.","specificNumbers":"6wk: fremanezumab 900mg SMD -0.55; 8wk: erenumab 140mg SMD -0.51; 12wk: erenumab 140mg SMD -0.48; drugs: erenumab, eptinezumab, fremanezumab, galcanezumab","methodology":"Systematic review and network meta-analysis. SCOPUS, PubMed, Cochrane, Embase through January 2019. RCTs of erenumab, eptinezumab, fremanezumab, galcanezumab vs placebo. Efficacy at 6, 8, and 12 weeks. Episodic and chronic migraine analyzed separately and combined.","limitations":"NMA relies on indirect comparisons. Head-to-head trials between anti-CGRP drugs are limited. Effect sizes are modest. Long-term (>12 week) comparisons not assessed. Dose comparisons limited."},{"rthcId":"RPEP-05588","title":"Nociceptor neurons promote IgE class switch in B cells.","authors":"Mathur, Shreya; Wang, Jo-Chiao; Seehus, Corey R; Poirier, Florence; Crosson, Theo; Hsieh, Yu-Chen; Doyle, Benjamin; Lee, Seungkyu; Woolf, Clifford J; Foster, Simmie L; Talbot, Sebastien","year":2021,"journal":"JCI insight, 6(24)","doi":"10.1172/jci.insight.148510","pmid":"34727095","tags":["substance-p","neuropeptides","immune-function"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"Nociceptor ablation/silencing substantially reduced allergic inflammation and IgE production in airway and skin models. Substance P released from nociceptors promoted B cell antibody class switching to IgE and antibody-secreting cell formation. First evidence of nociceptor role in adaptive humoral immunity.","whyItMatters":"Allergies affect billions worldwide. If pain neurons drive IgE production through substance P, blocking this pathway could prevent allergic reactions at their source — a completely new therapeutic approach beyond antihistamines and steroids.","specificNumbers":"2 models: airway + skin allergy; nociceptor ablation/silencing reduced infiltration + IgE; substance P mediates B cell class switching","methodology":"Animal study. Genetic nociceptor ablation and pharmacological silencing. Airway and skin allergic inflammation models. IgE quantification. B cell class switching analysis. Substance P mechanistic studies.","limitations":"Mouse allergy models. Substance P's role in human allergic IgE production needs confirmation. Nociceptor ablation is not a practical therapy. NK1R antagonist (aprepitant) testing for allergy not included."},{"rthcId":"RPEP-05589","title":"Thymosin Alpha 1 Mitigates Cytokine Storm in Blood Cells From Coronavirus Disease 2019 Patients.","authors":"Matteucci, Claudia; Minutolo, Antonella; Balestrieri, Emanuela; Petrone, Vita; Fanelli, Marialaura; Malagnino, Vincenzo; Ianetta, Marco; Giovinazzo, Alessandro; Barreca, Filippo; Di Cesare, Silvia; De Marco, Patrizia; Miele, Martino Tony; Toschi, Nicola; Mastino, Antonio; Sinibaldi Vallebona, Paola; Bernardini, Sergio; Rogliani, Paola; Sarmati, Loredana; Andreoni, Massimo; Grelli, Sandro; Garaci, Enrico","year":2021,"journal":"Open forum infectious diseases, 8(1), ofaa588","doi":"10.1093/ofid/ofaa588","pmid":"33506065","tags":["thymosin-alpha-1","immune-function"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Thymosin alpha-1 mitigated cytokine storm in COVID-19 patient blood cells by reducing excessive inflammatory cytokine production without broad immunosuppression.","whyItMatters":"COVID-19 deaths are largely caused by cytokine storm, not the virus itself. A peptide that calms this storm without suppressing anti-viral immunity could save lives in severe cases.","specificNumbers":"Cytokine signaling genes upregulated in COVID-19; Tα1 mitigated cytokine expression; CD8+ T cell subset specifically inhibited","methodology":"Ex vivo study. Blood cells from COVID-19 patients treated with Tα1. Cytokine production measured. Inflammatory response modulation assessed.","limitations":"Ex vivo study (blood cells in a dish, not whole patient). Small patient sample implied. Tα1 effects on intact immune system during active infection may differ. Clinical outcome data from Tα1 COVID treatment not provided."},{"rthcId":"RPEP-05590","title":"Monoclonal Antibodies Targeting CGRP: From Clinical Studies to Real-World Evidence-What Do We Know So Far?","authors":"Mavridis, Theodoros; Deligianni, Christina I; Karagiorgis, Georgios; Daponte, Ariadne; Breza, Marianthi; Mitsikostas, Dimos D","year":2021,"journal":"Pharmaceuticals (Basel, Switzerland), 14(7)","doi":"10.3390/ph14070700","pmid":"34358126","tags":["cgrp","neuropeptides"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Real-world evidence for anti-CGRP monoclonal antibodies shows efficacy consistent with or exceeding clinical trial results, with maintained favorable safety profiles in routine clinical practice.","whyItMatters":"Real-world evidence confirms that the benefits of anti-CGRP drugs seen in carefully controlled trials translate to actual patient care — reassuring for both doctors and patients.","specificNumbers":"Drugs: erenumab, fremanezumab, galcanezumab, eptinezumab; Phase III + real-world data; CGRP + PACAP pathways","methodology":"Narrative review comparing randomized controlled trial data with real-world evidence studies for anti-CGRP monoclonal antibody migraine treatment.","limitations":"Real-world studies have inherent biases (selection, recall, reporting). Comparison between trial and real-world data is indirect. Long-term real-world data still accumulating."},{"rthcId":"RPEP-05591","title":"Randomized clinical trial shows no substantial modulation of empathy-related neural activation by intranasal oxytocin in autism.","authors":"Mayer, Annalina V; Wermter, Anne-Kathrin; Stroth, Sanna; Alter, Peter; Haberhausen, Michael; Stehr, Thomas; Paulus, Frieder M; Krach, Sören; Kamp-Becker, Inge","year":2021,"journal":"Scientific reports, 11(1), 15056","doi":"10.1038/s41598-021-94407-x","pmid":"34301983","tags":["oxytocin","neuropeptides"],"studyType":"clinical trial","evidenceStrength":"moderate","keyFinding":"Randomized clinical trial showed no substantial modulation of empathy-related behavioral or neural responses by intranasal oxytocin administration compared to placebo.","whyItMatters":"The \"oxytocin = empathy\" narrative has influenced research funding, therapeutic trials, and public understanding. This negative result recalibrates expectations and directs research toward oxytocin's actual effects rather than assumed ones.","specificNumbers":"N=25 males; double-blind crossover; 3 empathy tasks; bilateral amygdala increase for physical pain only; OXTR rs53576 no interaction","methodology":"Randomized controlled clinical trial. Intranasal oxytocin vs placebo. Empathy-related behavioral and brain response measures.","limitations":"Single-dose acute study. Empathy measurement tools may not capture all aspects of social cognition. Oxytocin effects may be context-dependent or appear only in specific populations."},{"rthcId":"RPEP-05592","title":"Injectable Magnetic-Responsive Short-Peptide Supramolecular Hydrogels: Ex Vivo and In Vivo Evaluation.","authors":"Mañas-Torres, Mari C; Gila-Vilchez, Cristina; Vazquez-Perez, Francisco J; Kuzhir, Pavel; Momier, David; Scimeca, Jean-Claude; Borderie, Arnaud; Goracci, Marianne; Burel-Vandenbos, Fanny; Blanco-Elices, Cristina; Rodriguez, Ismael A; Alaminos, Miguel; de Cienfuegos, Luis Álvarez; Lopez-Lopez, Modesto T","year":2021,"journal":"ACS applied materials & interfaces, 13(42), 49692-49704","doi":"10.1021/acsami.1c13972","pmid":"34645258","tags":["peptide-drug-design","collagen-peptides"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Injectable magnetic-responsive short-peptide supramolecular hydrogels demonstrated magnetically guided assembly ex vivo, providing spatially controllable scaffolds with potential for tissue engineering applications.","whyItMatters":"Precise scaffold placement is critical in tissue engineering but hard to achieve with injectable materials. Magnetic guidance adds a control dimension that could improve outcomes in regenerative surgery.","specificNumbers":"Fmoc-FF and Fmoc-RGD peptides; MNP incorporation; injectable without disruption; faster self-healing; biocompatible; 3D scaffold","methodology":"Biomaterials study. Short peptide hydrogel with magnetic nanoparticle incorporation. Injectable formulation. Magnetic field-guided assembly ex vivo. Supramolecular structure characterization.","limitations":"Ex vivo demonstration only. In vivo biocompatibility of magnetic nanoparticles in peptide hydrogels not fully assessed. Long-term magnetic nanoparticle effects unknown. Clinical magnetic field equipment requirements."},{"rthcId":"RPEP-05593","title":"Cysteinyl radicals in chemical synthesis and in nature.","authors":"McLean, Joshua T; Benny, Alby; Nolan, Mark D; Swinand, Glenna; Scanlan, Eoin M","year":2021,"journal":"Chemical Society reviews, 50(19), 10857-10894","doi":"10.1039/d1cs00254f","pmid":"34397045","tags":["peptide-drug-design","stapled-peptides"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Cysteinyl radicals enable novel peptide synthesis strategies including stapling and selective modifications, while also playing important roles in natural enzyme catalysis and redox biology.","whyItMatters":"New chemical reactions using cysteinyl radicals expand the toolkit for making peptide drugs, enabling modifications that are impossible with conventional chemistry.","specificNumbers":"Synthetic uses: lipidation, glycosylation, labeling, macrocyclization, stapling, desulfurization; biological: DNA repair, metabolism, photochemistry","methodology":"Narrative review of cysteinyl radical chemistry in both synthetic and biological contexts.","limitations":"Chemistry review. Radical reactions can be challenging to control. Scale-up for pharmaceutical manufacturing needs development. Selectivity may vary between peptide substrates."},{"rthcId":"RPEP-05594","title":"Effects of sodium-glucose cotransporter-2 inhibitors on appetite markers in patients with type 2 diabetes mellitus.","authors":"McMillin, Sara M; Pham, Mimi L; Sherrill, Christina H","year":2021,"journal":"Nutrition, metabolism, and cardiovascular diseases : NMCD, 31(8), 2507-2511","doi":"10.1016/j.numecd.2021.05.005","pmid":"34167866","tags":["ghrelin","obesity-metabolism","sglt2-inhibitors"],"studyType":"observational","evidenceStrength":"preliminary","keyFinding":"SGLT2 inhibitors did not increase appetite or alter ghrelin, leptin, or PYY levels at 1 or 12 weeks in 7 diabetic patients.","whyItMatters":"Understanding why SGLT2 inhibitors produce less weight loss than expected could help improve obesity treatment strategies.","specificNumbers":"N=7; timepoints: baseline, 1wk, 12wk; hormones: ghrelin, leptin, PYY; no significant changes; appetite trended down","methodology":"Prospective single-center observational pilot study. 7 adults (18-70 years) newly prescribed SGLT2 inhibitors. Fasting and postprandial appetite and hormones measured at baseline, 1 week, and 12 weeks.","limitations":"Very small sample (N=7). Pilot study without control group. Short follow-up. May be underpowered to detect small hormone changes."},{"rthcId":"RPEP-05595","title":"Bitter Taste Receptor T2R14 Modulates Gram-Positive Bacterial Internalization and Survival in Gingival Epithelial Cells.","authors":"Medapati, Manoj Reddy; Bhagirath, Anjali Yadav; Singh, Nisha; Schroth, Robert J; Bhullar, Rajinder P; Duan, Kangmin; Chelikani, Prashen","year":2021,"journal":"International journal of molecular sciences, 22(18)","doi":"10.3390/ijms22189920","pmid":"34576085","tags":["defensins","antimicrobial-peptides"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Knocking down the T2R14 bitter taste receptor in gingival epithelial cells significantly decreased the internalization of S. aureus, while S. mutans internalization was unaffected. The two bacteria also triggered distinct T2R14-dependent immune responses: S. aureus infection induced secretion of the antimicrobial peptide human β-defensin-2 (hBD-2), whereas S. mutans infection induced IL-8 secretion instead.\n\nAdditionally, when gum cells were primed with S. mutans competence stimulating peptide CSP-1, they inhibited the growth of S. aureus but not S. mutans — suggesting cross-species bacterial defense mediated through T2R14 signaling. The receptor's role in cytoskeletal reorganization appears to be the mechanism behind these differential internalization effects.","whyItMatters":"This research reveals that taste receptors in your gums are part of a sophisticated immune surveillance system. Understanding how these receptors trigger different defenses against different bacteria could open the door to new strategies for preventing oral infections, gum disease, and possibly even systemic infections that start in the mouth.","specificNumbers":"T2R14 KD decreased S. aureus internalization; hBD-2 for S. aureus; IL-8 for S. mutans; CSP-1 priming inhibited S. aureus growth","methodology":"The researchers used CRISPR-Cas9 gene editing to disable (knock down) the T2R14 receptor in human gingival epithelial cells. They then exposed these modified cells and normal cells to two types of Gram-positive bacteria — Staphylococcus aureus and Streptococcus mutans — and measured how well bacteria were internalized, whether bacterial growth was inhibited, and which immune molecules (defensin-2 and IL-8) were released. They also examined how the cell's internal skeleton changed during infection.","limitations":"This was a cell culture study using a single type of gum cell, so the results may not fully reflect what happens in living gum tissue where multiple cell types and immune cells interact. The study also did not test other Gram-positive bacteria beyond S. aureus and S. mutans, so the specificity of T2R14 responses across a wider range of oral pathogens is unknown."},{"rthcId":"RPEP-05596","title":"Expected values for gastrointestinal and pancreatic hormone concentrations in healthy volunteers in the fasting and postprandial state.","authors":"Meek, Claire L; Lewis, Hannah B; Burling, Keith; Reimann, Frank; Gribble, Fiona","year":2021,"journal":"Annals of clinical biochemistry, 58(2), 108-116","doi":"10.1177/0004563220975658","pmid":"33175577","tags":["glp-1-peptides","gip-peptides","pyy-peptide"],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"Established reference ranges for GLP-1, GIP, PYY, glucagon, insulin, and glucose in 28 healthy volunteers in fasting and postprandial states.","whyItMatters":"Without knowing what is normal, researchers cannot identify what is abnormal. These reference values are essential for gut hormone research.","specificNumbers":"N=28; 12M/16F; age 31.3; BMI 24.9; OGTT + meal test; 4h sampling; GLP-1, GIP, PYY, glucagon, insulin, glucose, FFA, C-peptide, proinsulin","methodology":"Prospective study. 28 healthy volunteers (12 men, 16 women, mean age 31.3, mean BMI 24.9). Randomized crossover: 75g OGTT and standardized meal test. Blood sampling for 4 hours after each.","limitations":"Relatively small sample (N=28). Single ethnic/geographic population. Reference ranges may vary by age, ethnicity, and body composition."},{"rthcId":"RPEP-05597","title":"Enhanced Neurokinin-1 Receptor Expression Is Associated with Human Dental Pulp Inflammation and Pain Severity.","authors":"Mehboob, Riffat; Hassan, Sana; Gilani, Syed Amir; Hassan, Amber; Tanvir, Imrana; Waseem, Humaira; Hanif, Asif","year":2021,"journal":"BioMed research international, 2021, 5593520","doi":"10.1155/2021/5593520","pmid":"34041298","tags":["substance-p","neuropeptides"],"studyType":"observational","evidenceStrength":"preliminary","keyFinding":"NK-1R was significantly overexpressed in inflamed dental pulp (score 2.4 vs 0.2, p<0.001) and correlated with higher pain severity.","whyItMatters":"Dental pain affects millions. Targeting the SP/NK-1R pathway could provide a new class of dental pain treatments.","specificNumbers":"N=10+10; NK-1R score 2.4±0.516 vs 0.2±0.4216; p=0.000; mean VAS 7.0±2.0; intense NK-1R = higher pain","methodology":"Case-control study. 10 inflamed and 10 healthy dental pulp samples. Immunohistochemistry for NK-1R. Pain assessed with VAS and McGill Pain Questionnaire.","limitations":"Very small sample (N=20). Single measurement point. Cannot prove NK-1R causes pain vs. being a consequence of inflammation."},{"rthcId":"RPEP-05598","title":"Neuropathological explanation of minimal COVID-19 infection rate in newborns, infants and children - a mystery so far. New insight into the role of Substance P.","authors":"Mehboob, Riffat; Lavezzi, Anna Maria","year":2021,"journal":"Journal of the neurological sciences, 420, 117276","doi":"10.1016/j.jns.2020.117276","pmid":"33360484","tags":["substance-p","neuropeptides"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"The authors hypothesize that age-dependent differences in Substance P (SP) levels explain why children rarely develop severe COVID-19 while elderly patients suffer the worst outcomes. Substance P is a neuropeptide produced in the brainstem's spinal trigeminal nucleus that drives inflammation in the airways. The authors propose that higher SP activity in elderly patients amplifies the inflammatory cascade in COVID-19, worsening respiratory illness.\n\nTheir central recommendation: NK-1R antagonists — drugs that block the Substance P receptor — should be urgently investigated as COVID-19 treatments. These drugs are already FDA-approved for other uses (notably as anti-nausea medications), making rapid repurposing feasible.","whyItMatters":"This hypothesis connects two well-established observations — children's resistance to severe COVID-19 and age-dependent changes in neuropeptide signaling — through the lens of Substance P biology. If correct, it points to an already-available drug class (NK-1R antagonists like aprepitant) as a potential treatment. The paper also highlights the broader role of neuropeptides in respiratory inflammation, relevant far beyond COVID-19.","specificNumbers":"Substance P from spinal trigeminal nucleus · Age-dependent expression hypothesis · NK-1R antagonist proposed as intervention · Based on neuropathological observations from SIDS research","methodology":"This is a hypothesis paper drawing on the authors' neuropathological experience at the Lino Rossi Research Center in Milan, which studies unexpected infant death and SIDS. They combine observations about brainstem neuropeptide development with published COVID-19 epidemiological and clinical data to construct their theory about Substance P's role in age-dependent disease severity.","limitations":"This is a hypothesis paper — no experimental data is presented. The authors did not directly measure Substance P levels in children versus elderly patients with COVID-19. Many other factors contribute to age-dependent COVID-19 severity (immune maturation, ACE2 expression, comorbidities), and the SP hypothesis is one of several competing explanations. The causal chain from brainstem SP production to respiratory inflammation severity in COVID-19 involves multiple unverified steps."},{"rthcId":"RPEP-05599","title":"Prognostic Significance of Substance P/Neurokinin 1 Receptor and Its Association with Hormonal Receptors in Breast Carcinoma.","authors":"Mehboob, Riffat; Gilani, Syed Amir; Hassan, Amber; Sadaf; Tanvir, Imrana; Javaid, Shaista; Khalid, Sidra; Hasan, Sana; Waseem, Humaira; Alwazzan, Ahmad; Munoz, Miguel","year":2021,"journal":"BioMed research international, 2021, 5577820","doi":"10.1155/2021/5577820","pmid":"34692834","tags":["substance-p","neuropeptides"],"studyType":"observational","evidenceStrength":"preliminary","keyFinding":"SP and NK-1R are overexpressed in breast carcinoma, with significant association between tumor grade and expression intensity.","whyItMatters":"If substance P drives breast cancer progression, NK-1R antagonists (already available as anti-nausea drugs) could potentially be repurposed for cancer treatment.","specificNumbers":"N=34; SP positive: 61% grade III, 88% grade II, 67% grade I; +3 staining: 64.2% grade III, 12.5% grade II","methodology":"Cross-sectional study of 34 breast cancer cases. Immunohistochemistry for SP and NK-1R. Compared with ER, PR, HER2, and Ki-67 markers.","limitations":"Small sample (N=34). Cross-sectional design cannot prove SP drives progression. No therapeutic intervention tested. Limited grade I cases (N=3)."},{"rthcId":"RPEP-05600","title":"Probiotic engineering strategies for the heterologous production of antimicrobial peptides.","authors":"Mejía-Pitta, Adriana; Broset, Esther; de la Fuente-Nunez, Cesar","year":2021,"journal":"Advanced drug delivery reviews, 176, 113863","doi":"10.1016/j.addr.2021.113863","pmid":"34273423","tags":[],"studyType":"review","evidenceStrength":"review","keyFinding":"Engineered probiotic bacteria can be genetically modified to produce antimicrobial peptides (AMPs) directly inside the gut, providing a living drug delivery system that continuously manufactures antibiotics right where they're needed. This review covers the current state of AMP-producing probiotics, discussing how oral delivery via probiotic bacteria protects AMPs from degradation in the digestive tract — solving one of the biggest challenges in peptide drug delivery.\n\nKey applications include treating drug-resistant enteric pathogens (gut infections caused by antibiotic-resistant bacteria) and actively remodeling the gut microbiome in real time. The review also addresses strategies to enhance probiotic colonization of the gut for sustained AMP delivery.","whyItMatters":"Antibiotic resistance is one of the most pressing public health crises, and drug-resistant gut infections are particularly dangerous. Antimicrobial peptides are promising alternatives, but delivering them orally is normally impossible because stomach acid and digestive enzymes destroy them. Engineering probiotic bacteria to produce AMPs in the gut bypasses this problem entirely — the bacteria survive digestion and continuously produce fresh peptides at the infection site.","specificNumbers":"Published in Advanced Drug Delivery Reviews (high-impact journal) · Covers AMP-producing probiotics · Focus on drug-resistant enteric pathogen treatment · Strategies for enhanced gut colonization reviewed","methodology":"Narrative review surveying published research on engineered probiotic bacteria that produce antimicrobial peptides, including genetic engineering strategies, oral delivery methods, gut colonization enhancement, and therapeutic applications.","limitations":"As a review, this paper synthesizes existing research without presenting new data. The abstract doesn't detail systematic search criteria or evidence grading. Most AMP-producing probiotic work remains preclinical, so the review primarily covers animal studies and in vitro proof-of-concept work rather than clinical applications."},{"rthcId":"RPEP-05601","title":"Efficacy of Self-Administered Intranasal Oxytocin on Alcohol Use and Craving After Detoxification in Patients With Alcohol Dependence. A Double-Blind Placebo-Controlled Trial.","authors":"Melby, Katrine; Gråwe, Rolf W; Aamo, Trond O; Skovlund, Eva; Spigset, Olav","year":2021,"journal":"Alcohol and alcoholism (Oxford, Oxfordshire), 56(5), 565-572","doi":"10.1093/alcalc/agaa133","pmid":"33352584","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05602","title":"Oxytocin, Erectile Function and Sexual Behavior: Last Discoveries and Possible Advances.","authors":"Melis, Maria Rosaria; Argiolas, Antonio","year":2021,"journal":"International journal of molecular sciences, 22(19)","doi":"10.3390/ijms221910376","pmid":"34638719","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05603","title":"Advances in the detection of growth hormone releasing hormone synthetic analogs.","authors":"Memdouh, Siham; Gavrilović, Ivana; Ng, Kelsey; Cowan, David; Abbate, Vincenzo","year":2021,"journal":"Drug testing and analysis, 13(11-12), 1871-1887","doi":"10.1002/dta.3183","pmid":"34665524","tags":["ghrh-analogs","peptide-drug-design"],"studyType":"in vitro","evidenceStrength":"moderate","keyFinding":"Identified 19 in vitro metabolites of 4 GHRH analogs and developed an LC-MS/MS urine detection method meeting WADA's 1 ng/mL performance limit.","whyItMatters":"Athletes may use GHRH analogs to boost growth hormone. Better detection methods protect fair competition.","specificNumbers":"4 analogs: sermorelin, tesamorelin, CJC-1295, CJC-1295 DAC; 19 metabolites; LOD ≤1 ng/mL; LC-MS/MS","methodology":"In vitro metabolism studies of sermorelin, tesamorelin, CJC-1295, and CJC-1295 DAC. Synthesized and characterized 19 metabolites. Developed and validated LC-MS/MS detection method in fortified urine.","limitations":"In vitro metabolism may not fully represent in vivo metabolism. Method validated in fortified (spiked) urine, not real doping samples. Real-world detection has not been demonstrated yet."},{"rthcId":"RPEP-05604","title":"Structural effects driven by rare point mutations in amylin hormone, the type II diabetes-associated peptide.","authors":"Mendes, Wendy S; Franco, Octavio L; Alencar, Sergio A; Porto, William F","year":2021,"journal":"Biochimica et biophysica acta. General subjects, 1865(8), 129935","doi":"10.1016/j.bbagen.2021.129935","pmid":"34044067","tags":["amylin","metabolic-health"],"studyType":"mechanistic","evidenceStrength":"preliminary","keyFinding":"Both S20G and G33R amylin mutations increase aggregation potential, with structural analysis suggesting the second alpha-helix is key to aggregation behavior.","whyItMatters":"Understanding which mutations make amylin more toxic could lead to personalized diabetes treatment and better drug design.","specificNumbers":"Amylin: 37 aa; S20G: East Asian; G33R: European; both increase aggregation; pramlintide comparison; molecular dynamics simulations","methodology":"Computational study using aggrescan server, SNP functional effect predictors, and molecular dynamics simulations. Compared wild-type amylin, S20G, G33R, and pramlintide.","limitations":"Computational study without experimental validation. Population frequencies of these mutations are low. Clinical significance of G33R is not proven."},{"rthcId":"RPEP-05605","title":"Immunogenicity in humans of a transdermal multipeptide melanoma vaccine administered with or without a TLR7 agonist.","authors":"Meneveau, Max O; Petroni, Gina R; Salerno, Elise P; Lynch, Kevin T; Smolkin, Mark; Woodson, Elizabeth; Chianese-Bullock, Kimberly A; Olson, Walter C; Deacon, Donna; Patterson, James W; Grosh, William W; Slingluff, Craig L","year":2021,"journal":"Journal for immunotherapy of cancer, 9(5)","doi":"10.1136/jitc-2020-002214","pmid":"34035112","tags":["peptide-drug-design","immune-function"],"studyType":"clinical trial","evidenceStrength":"moderate","keyFinding":"Twenty-eight melanoma patients were randomized to four adjuvant groups for transdermal peptide vaccination (12 melanoma peptides + tetanus helper peptide + GM-CSF). CD8+ T cell responses to transdermal vaccination in DMSO occurred in 83% (group 3) and 86% (group 4) of participants, dramatically exceeding responses with IFA: 29% (group 1) and 14% (group 2). CD4+ T cell responses to tetanus peptide occurred in 61% overall, with large durable responses in DMSO groups. However, 5/7 patients receiving DMSO + imiquimod developed severe rash, one dose-limiting. Ten-year overall survival was 67% and disease-free survival was 44%.","whyItMatters":"This trial proves that cancer peptide vaccines can be delivered through the skin, achieving far higher immune response rates than traditional injection methods. If validated in larger trials, transdermal vaccination could make cancer immunization less invasive, more effective, and more accessible — potentially transforming how therapeutic cancer vaccines are administered.","specificNumbers":"N=28; 12 peptides + tetanus helper; DMSO CD8+ response 83-86%; IFA 14-29%; 10yr OS 67%; DFS 44%; 5/7 severe rash with imiquimod","methodology":"Phase I/II randomized clinical trial in 28 melanoma patients across four adjuvant groups. Peptides applied topically on days 1, 8, and 15, then injected intradermally/subcutaneously every 3 weeks for 6 cycles. Immune responses measured by ELIspot assay for CD8+ and CD4+ T cell responses. Toxicities recorded and 10-year survival outcomes tracked.","limitations":"Small trial (n=28) without an unvaccinated control group. The 10-year survival cannot be directly attributed to vaccination. Imiquimod caused unacceptable toxicity in most recipients. The DMSO delivery mechanism needs further pharmacokinetic characterization. The trial enrolled patients across a range of melanoma stages, and the small group sizes limit statistical comparisons between adjuvants."},{"rthcId":"RPEP-05606","title":"LC-HRMS characterization of the skin pigmentation and sexual enhancers melanotan II and bremelanotide sold on the black market of performance and image enhancing drugs.","authors":"Mestria, Serena; Odoardi, Sara; Frison, Giampietro; Strano Rossi, Sabina","year":2021,"journal":"Drug testing and analysis, 13(4), 876-882","doi":"10.1002/dta.2986","pmid":"33245851","tags":["melanocortin-peptides","peptide-drug-design"],"studyType":"in vitro","evidenceStrength":"moderate","keyFinding":"Using liquid chromatography coupled with high-resolution Orbitrap mass spectrometry (LC-HRMS), researchers successfully identified melanotan II and bremelanotide in 8 confiscated samples without requiring reference standards.\n\nIdentification was achieved through three complementary approaches: accurate mass measurement of protonated molecular ions (MH+), analysis of isotopic patterns and relative isotopic abundance (RIA) values, and accurate mass measurement of collision-induced fragment ions.\n\nThe samples had been confiscated by police alongside anabolic steroids, hormone modulators, sexual enhancers, and stimulants — illustrating that these peptides circulate within the broader black market for performance and image-enhancing drugs (PIEDs).","whyItMatters":"The black market for peptides is largely unregulated, and buyers have no way to verify what they're actually injecting. Forensic labs need reliable methods to identify these compounds when they're seized by law enforcement. This study demonstrates that high-resolution mass spectrometry can identify peptide PIEDs without reference standards — a critical capability since many black market peptides don't have commercially available reference materials for forensic testing.","specificNumbers":"8 samples; melanotan II + bremelanotide identified; LC-HRMS Orbitrap; MH+ accurate mass; isotopic patterns; fragmentation analysis","methodology":"Eight unknown samples confiscated by police were analyzed using liquid chromatography coupled with high-resolution/high-accuracy Orbitrap mass spectrometry (LC-HRMS). Compounds were characterized through accurate mass measurements, isotopic pattern analysis, relative isotopic abundance calculations, and collision-induced dissociation (fragmentation) experiments. No certified reference standards were used — identification was based entirely on structural characterization from mass spectrometric data.","limitations":"This is a forensic characterization study only — no quantification of purity, potency, or contaminants was performed. No assessment of health risks from the confiscated products was conducted. Only 8 samples were analyzed, and only two peptide compounds were identified. The study doesn't address whether the products contained the labeled doses or had dangerous impurities."},{"rthcId":"RPEP-05607","title":"Antimicrobial Peptides: The Promising Therapeutics for Cutaneous Wound Healing.","authors":"Miao, Fengze; Li, Ying; Tai, Zongguang; Zhang, Yong; Gao, Yue; Hu, Menghong; Zhu, Quangang","year":2021,"journal":"Macromolecular bioscience, 21(10), e2100103","doi":"10.1002/mabi.202100103","pmid":"34405955","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05608","title":"Rational design of a potent macrocyclic peptide inhibitor targeting the PD-1/PD-L1 protein-protein interaction.","authors":"Miao, Qi; Zhang, Wanheng; Zhang, Kuojun; Li, He; Zhu, Jidong; Jiang, Sheng","year":2021,"journal":"RSC advances, 11(38), 23270-23279","doi":"10.1039/d1ra03118j","pmid":"35479790","tags":["peptide-drug-design","immune-function"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"JMPDP-027 cyclic peptide blocked PD-1/PD-L1 with EC50 of 5.9 nM (comparable to pembrolizumab) and showed potent in vivo anticancer activity.","whyItMatters":"Antibody checkpoint inhibitors revolutionized cancer treatment but are expensive. Peptide alternatives could make immunotherapy more accessible.","specificNumbers":"EC50 5.9 nM; comparable to pembrolizumab; serum stable; no toxicity; in vivo efficacy ≈ anti-PD-L1 mAb","methodology":"Rational design and optimization of macrocyclic peptide. T cell restoration assay, serum stability, cytotoxicity, and CT26 colon carcinoma mouse model.","limitations":"Single mouse tumor model. Manufacturing scalability not demonstrated. Long-term pharmacokinetics and safety unknown. Head-to-head with pembrolizumab not done in vivo."},{"rthcId":"RPEP-05609","title":"Enzyme-Agnostic Lysosomal Screen Identifies New Legumain-Cleavable ADC Linkers.","authors":"Miller, Jared T; Vitro, Caitlin N; Fang, Siteng; Benjamin, Samantha R; Tumey, L Nathan","year":2021,"journal":"Bioconjugate chemistry, 32(4), 842-858","doi":"10.1021/acs.bioconjchem.1c00124","pmid":"33788548","tags":["peptide-drug-design"],"studyType":"in vitro","evidenceStrength":"moderate","keyFinding":"From a screen of 75 peptide FRET pairs, asparagine-containing peptides emerged as being cleaved far more rapidly than traditional valine-citrulline linkers by lysosomal extracts while maintaining excellent plasma stability. These linkers were cleaved by legumain (an asparaginyl endopeptidase overexpressed in many cancers). MMAE-containing ADCs with the new linkers showed cytotoxicity comparable to standard ValCit ADCs. Critically, the Asn-containing linkers were completely stable to human neutrophil elastase (thought to cause ADC-related neutropenia and thrombocytopenia). Serum stability was excellent: >85% drug retention after 1 week in mouse and human serum, and <10% cleavage of FRET pairs after 18 hours.","whyItMatters":"ADC toxicity from off-target drug release is a major clinical problem limiting their use. Current valine-citrulline linkers are cut by neutrophil elastase and other enzymes in the blood, causing side effects. These new legumain-cleavable linkers could make ADC therapy significantly safer while maintaining cancer-killing potency, potentially broadening the patient population that can benefit from these drugs.","specificNumbers":"75 peptides screened; Asn linkers; legumain-cleavable; MMAE ADCs; >85% drug retained 1wk serum; <10% cleavage 18h serum; 0% neutrophil elastase cleavage","methodology":"Researchers designed 75 peptide FRET (fluorescence resonance energy transfer) pairs and screened them for cleavage by lysosomal extracts and plasma in an enzyme-agnostic approach (not targeting any specific enzyme). Hits were identified and the cleaving enzyme was determined through catabolism studies. Lead peptide linkers (particularly AsnAsn) were incorporated into MMAE-containing ADCs. These were tested for cytotoxicity against cancer cells, serum stability in mouse and human serum, and resistance to neutrophil elastase.","limitations":"All data are in vitro and cell-based — no in vivo tumor efficacy studies were conducted. Legumain expression varies between cancer types, which could limit the broad applicability of these linkers. Manufacturing complexity of the new linkers compared to standard ValCit was not assessed. Long-term stability and pharmacokinetics in animal models remain untested."},{"rthcId":"RPEP-05610","title":"Phase 1b Evaluation of Abaloparatide Solid Microstructured Transdermal System (Abaloparatide-sMTS) in Postmenopausal Women with Low Bone Mineral Density.","authors":"Miller, Paul D; Troy, Steven; Weiss, Richard J; Annett, Miriam; Schense, Jason; Williams, Setareh A; Mitlak, Bruce","year":2021,"journal":"Clinical drug investigation, 41(3), 277-285","doi":"10.1007/s40261-021-01008-7","pmid":"33638863","tags":["abaloparatide","osteoporosis"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"A transdermal microneedle patch delivering abaloparatide (an osteoporosis peptide drug) was successfully self-administered by all 22 postmenopausal women enrolled in the trial, with a 99.7% success rate on first application. The patch delivered consistent drug levels over 29 days, with bone formation marker s-PINP increasing by 45.4% at Day 15 and 64.4% at Day 29 — similar to results seen with the standard subcutaneous injection.\n\nThe patch was applied to the thigh for 5 minutes daily at a 300 μg dose. Drug absorption was rapid (peak levels reached in about 20 minutes). Side effects were mostly mild application-site reactions (redness, pain, swelling), and no one dropped out due to adverse events. Patient acceptability scored approximately 4.5 out of 5.","whyItMatters":"Abaloparatide currently requires daily subcutaneous injections, which many osteoporosis patients find burdensome and which limits treatment adherence. A painless transdermal patch that patients can apply themselves could dramatically improve how many people actually stick with treatment — potentially reducing fractures in a population where medication adherence is notoriously poor.","specificNumbers":"n=22 · 300 μg daily dose · 5-min application · s-PINP +45.4% Day 15, +64.4% Day 29 · Tmax 0.33 h · Cmax 447 pg/mL · 99.7% self-admin success · 4.5/5 acceptability · 29 days · mean age 65.2 years","methodology":"Single-arm, open-label Phase 1b clinical trial. 22 healthy postmenopausal women (ages 50-85) with low bone mineral density were trained to self-administer the abaloparatide transdermal patch to the thigh daily for 29 days. Pharmacokinetics, bone formation markers, patient experience, and safety were measured.","limitations":"Small sample size (n=22) and single-arm design without a comparator group or placebo control. The 29-day duration is too short to assess fracture risk reduction or long-term BMD changes. Participants were trained and supervised, which may inflate self-administration success rates compared to real-world use."},{"rthcId":"RPEP-05611","title":"Anti-Inflammatory and Anti-Allergic Effects of Saponarin and Its Impact on Signaling Pathways of RAW 264.7, RBL-2H3, and HaCaT Cells.","authors":"Min, Seon-Young; Park, Che-Hwon; Yu, Hye-Won; Park, Young-Jin","year":2021,"journal":"International journal of molecular sciences, 22(16)","doi":"10.3390/ijms22168431","pmid":"34445132","tags":["cathelicidins","antimicrobial-peptides","skin-health"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Saponarin showed anti-inflammatory, anti-allergic, and skin barrier-enhancing effects including LL-37 induction across three cell models.","whyItMatters":"A natural compound that fights inflammation, allergies, and strengthens the skin barrier could help treat atopic dermatitis and other skin conditions.","specificNumbers":"Saponarin 40-100 μM; reduced TNF-α, IL-1β, iNOS, COX-2; blocked ERK/p38; inhibited degranulation; induced LL-37, HAS-3, AQP3","methodology":"In vitro study using LPS-stimulated RAW264.7 macrophages, IgE-stimulated RBL-2H3 basophilic cells, and TNF-α/IFN-γ-stimulated HaCaT keratinocytes.","limitations":"All in vitro data. Effective concentrations (40-100 μM) may be difficult to achieve in skin. No animal or human testing."},{"rthcId":"RPEP-05612","title":"The Role of Tirzepatide, Dual GIP and GLP-1 Receptor Agonist, in the Management of Type 2 Diabetes: The SURPASS Clinical Trials.","authors":"Min, Thinzar; Bain, Stephen C","year":2021,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 12(1), 143-157","doi":"10.1007/s13300-020-00981-0","pmid":"33325008","tags":["glp-1-peptides","gip-peptides","obesity-metabolism"],"studyType":"Review","evidenceStrength":"Moderate","keyFinding":"Tirzepatide is a synthetic 39-amino-acid peptide that activates both GIP and GLP-1 receptors simultaneously — a first-in-class 'twincretin.' Early clinical trials (phase 1 and 2) demonstrated potent glucose-lowering and weight loss effects with a side effect profile comparable to existing GLP-1 receptor agonists.\n\nThe dual-agonist concept was built on research showing that co-infusion of GIP and GLP-1 together produces synergistic effects — significantly greater insulin response and glucagon suppression than either hormone alone. Tirzepatide is built on the native GIP sequence with modifications that also activate the GLP-1 receptor, representing a new pharmacological approach to type 2 diabetes.","whyItMatters":"GLP-1 receptor agonists like semaglutide were already transforming diabetes treatment, but tirzepatide's dual-receptor approach takes the concept further. By harnessing both incretin pathways simultaneously, tirzepatide has since shown in the completed SURPASS trials even greater glucose lowering and weight loss than single-target GLP-1 drugs. This review captured the state of knowledge just before those landmark phase 3 results, documenting the scientific rationale that led to one of the most significant diabetes drugs in recent history.","specificNumbers":"39 amino acids · dual GIP/GLP-1 agonist · based on native GIP sequence · SURPASS phase 3 program · phase 1-2 data showing potent glucose + weight effects","methodology":"Narrative review summarizing preclinical data, phase 1, and phase 2 clinical trial results for tirzepatide in type 2 diabetes, along with an overview of the planned SURPASS phase 3 clinical trial program.","limitations":"This review was published before the SURPASS phase 3 trial results were available, so it relies on early-phase data only. Long-term efficacy, safety, and cardiovascular outcomes were unknown at the time of publication. The review does not include head-to-head comparisons with GLP-1 agonists from controlled trials."},{"rthcId":"RPEP-05613","title":"Protein Aggregation Inhibitors as Disease-Modifying Therapies for Polyglutamine Diseases.","authors":"Minakawa, Eiko N; Nagai, Yoshitaka","year":2021,"journal":"Frontiers in neuroscience, 15, 621996","doi":"10.3389/fnins.2021.621996","pmid":"33642983","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05614","title":"Bremelanotide and flibanserin for low sexual desire in women: the fallacy of regulatory precedent.","authors":"Mintzes, Barbara; Tiefer, Leonore; Cosgrove, Lisa","year":2021,"journal":"Drug and therapeutics bulletin, 59(12), 185-188","doi":"10.1136/dtb.2021.000020","pmid":"34642243","tags":["melanocortin-peptides"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Flibanserin added ~0.5 satisfying sexual events/month; bremelanotide added none by primary outcome. Both approvals involved shifted endpoints and contested indications.","whyItMatters":"Regulatory decisions based on weak evidence can set precedents that lower the bar for future drug approvals.","specificNumbers":"Flibanserin: +0.5 SSE/month; bremelanotide: no primary endpoint benefit; flibanserin approved on 3rd attempt; shifted primary outcomes","methodology":"Critical regulatory analysis of clinical trial data, endpoint shifts, advocacy campaigns, and approval processes for flibanserin and bremelanotide.","limitations":"Critical analysis from one perspective. Drug regulators and manufacturers may disagree. Patient-reported outcomes like desire are inherently subjective."},{"rthcId":"RPEP-05615","title":"Furan warheads for covalent trapping of weak protein-protein interactions: cross-linking of thymosin β4 to actin.","authors":"Miret-Casals, Laia; Vannecke, Willem; Hoogewijs, Kurt; Arauz-Garofalo, Gianluca; Gay, Marina; Díaz-Lobo, Mireia; Vilaseca, Marta; Ampe, Christophe; Van Troys, Marleen; Madder, Annemieke","year":2021,"journal":"Chemical communications (Cambridge, England), 57(49), 6054-6057","doi":"10.1039/d1cc01731d","pmid":"34036992","tags":["thymosin-beta-4","peptide-drug-design"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Furan warheads on Tβ4 variants successfully cross-linked to actin at lysine residues, demonstrating covalent trapping of a weak protein-protein interaction.","whyItMatters":"Many disease-relevant protein interactions are too weak for traditional drugs. Covalent trapping opens new therapeutic possibilities.","specificNumbers":"Furan warhead; site-specific cross-linking; lysine targets on actin; Tβ4-actin weak PPI model; known 3D structure","methodology":"In vitro biochemical study. Designed furan-armed Tβ4 variants. Tested cross-linking to actin. Identified target residues.","limitations":"In vitro proof of concept only. Selectivity in complex biological systems not tested. Clinical applicability unknown."},{"rthcId":"RPEP-05616","title":"Candida albicans Modulates Murine and Human Beta Defensin-1 during Vaginitis.","authors":"Miró, María Soledad; Caeiro, Juan Pablo; Rodriguez, Emilse; Vargas, Lara; Vigezzi, Cecilia; Icely, Paula A; Castillo, Graciela D V; Azcurra, Ana I; Abiega, Claudio D; Riera, Fernando O; Sotomayor, Claudia E","year":2021,"journal":"Journal of fungi (Basel, Switzerland), 8(1)","doi":"10.3390/jof8010020","pmid":"35049960","tags":["defensins","antimicrobial-peptides"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"C. albicans aspartate proteinase and lipase severely diminished BD1 expression in RVVC patients, enabling an immune escape strategy for chronic infection.","whyItMatters":"Recurrent yeast infections are common and difficult to treat. Understanding how Candida evades defenses could lead to new treatment strategies.","specificNumbers":"BD1 mRNA + protein severely reduced in RVVC; C. albicans aspartate proteinase + lipase responsible; BD3 also measured; cytokine profile assessed","methodology":"Combined mouse VVC model with analysis of cervicovaginal lavage from VVC and RVVC patients. Measured BD1 and BD3 mRNA and protein, plus cytokine profiles.","limitations":"Small clinical sample sizes typical for this type of study. Mouse vaginal model may not perfectly replicate human infections."},{"rthcId":"RPEP-05617","title":"The vaginal microbiota and innate immunity after local excisional treatment for cervical intraepithelial neoplasia.","authors":"Mitra, Anita; MacIntyre, David A; Paraskevaidi, Maria; Moscicki, Anna-Barbara; Mahajan, Vishakha; Smith, Ann; Lee, Yun S; Lyons, Deirdre; Paraskevaidis, Evangelos; Marchesi, Julian R; Bennett, Phillip R; Kyrgiou, Maria","year":2021,"journal":"Genome medicine, 13(1), 176","doi":"10.1186/s13073-021-00977-w","pmid":"34736529","tags":["defensins","antimicrobial-peptides"],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"CIN excision reduced vaginal beta-defensin-1 and SLPI levels but did not correct Lactobacillus depletion or elevated cytokines.","whyItMatters":"Understanding why the vaginal environment stays unhealthy after treatment could lead to strategies that reduce cervical cancer recurrence risk.","specificNumbers":"N=103+39; CST IV 20% vs 3%; hBD-1 and SLPI decreased (p<0.0001); IL-1β/IL-8 stayed elevated; P. bivia elevated post-treatment","methodology":"Observational study. 103 women sampled at CIN excision and 6-month follow-up. 39 untreated healthy controls. Metataxonomics for microbiome; ELISA for AMPs and cytokines.","limitations":"Observational design. 6-month follow-up may be too short. No intervention to restore microbiome was tested. Hormone status and other factors not fully controlled."},{"rthcId":"RPEP-05618","title":"Oral Supplementation of Collagen Peptides Improves Skin Hydration by Increasing the Natural Moisturizing Factor Content in the Stratum Corneum: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.","authors":"Miyanaga, Miho; Uchiyama, Taro; Motoyama, Akira; Ochiai, Nobuhiko; Ueda, Osamu; Ogo, Masashi","year":2021,"journal":"Skin pharmacology and physiology, 34(3), 115-127","doi":"10.1159/000513988","pmid":"33774639","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05619","title":"Adherence and persistence among patients with type 2 diabetes initiating dulaglutide compared with semaglutide and exenatide BCise: 6-month follow-up from US real-world data.","authors":"Mody, Reema; Yu, Maria; Nepal, Bal; Konig, Manige; Grabner, Michael","year":2021,"journal":"Diabetes, obesity & metabolism, 23(1), 106-115","doi":"10.1111/dom.14195","pmid":"32945083","tags":["glp-1-peptides"],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"Dulaglutide had significantly higher 6-month adherence (59.7%) and persistence vs. semaglutide (42.7%) and exenatide BCise (40.3%).","whyItMatters":"A drug only works if patients take it. Better adherence means better real-world diabetes control and outcomes.","specificNumbers":"3,852 dulaglutide:semaglutide pairs; 1,879 dulaglutide:exenatide pairs; adherence PDC≥80%: 59.7% vs 42.7% vs 40.3%; HR 0.71 and 0.59","methodology":"Retrospective claims analysis from HealthCore database. Propensity-matched new users: 3,852 dulaglutide:semaglutide pairs; 1,879 dulaglutide:exenatide BCise pairs. Index period Feb-Dec 2018.","limitations":"Claims data cannot explain why patients stopped. Does not measure clinical outcomes like HbA1c or weight. Early semaglutide adopters may differ from later users. Funded by Lilly (dulaglutide manufacturer)."},{"rthcId":"RPEP-05620","title":"Immunoliposomes bearing lymphocyte activation gene 3 fusion protein and P5 peptide: A novel vaccine for breast cancer.","authors":"Mohammadian Haftcheshmeh, Saeed; Zamani, Parvin; Mashreghi, Mohammad; Nikpoor, Amin Reza; Tavakkol-Afshari, Jalil; Jaafari, Mahmoud Reza","year":2021,"journal":"Biotechnology progress, 37(2), e3095","doi":"10.1002/btpr.3095","pmid":"33118322","tags":["peptide-drug-design","immune-function"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"LAG3-Ig-P5-immunoliposomes outperformed soluble LAG3-Ig + P5 across all measured outcomes:\n\n- Dendritic cell maturation: markedly induced by liposome-conjugated LAG3-Ig through multivalent MHC class II binding, more efficiently than free LAG3-Ig\n- T cell responses: higher percentages of both CD4+ and CD8+ T cells in the spleen\n- Tumor infiltration: more rapid and pronounced infiltration of effector T cells into tumor tissue\n- Anti-tumor efficacy: greater tumor regression and prolonged survival in treated mice\n\nThe PEGylated liposome format enhanced LAG3-Ig's adjuvant activity by presenting it in a multivalent configuration that amplified its interaction with immune cells.","whyItMatters":"HER2-positive breast cancer affects about 20% of breast cancer patients and, despite existing therapies like trastuzumab, remains challenging to treat in advanced stages. Peptide-based cancer vaccines have shown promise but often generate weak immune responses on their own. This study demonstrates that presenting peptide antigens and immune adjuvants on liposomes dramatically improves vaccine efficacy — an approach that could be applied to other cancer peptide vaccines and potentially combined with existing HER2-targeted therapies.","specificNumbers":"LAG3-Ig + P5 on PEGylated liposomes; enhanced DC maturation; higher CD4+/CD8+ infiltration; greater tumor regression + survival","methodology":"Researchers prepared PEGylated liposomes with surface-conjugated LAG3-Ig (immune adjuvant) and P5 peptide (HER2/neu-derived tumor antigen). The immunoliposomes were characterized and tested in BALB/c mice bearing TUBO HER2/neu-positive breast tumors. Outcomes included dendritic cell maturation markers, splenic CD4+ and CD8+ T cell percentages, T cell infiltration into tumors, tumor growth measurement, and survival. Results were compared against soluble (non-liposomal) LAG3-Ig + P5 immunotherapy.","limitations":"The study was conducted in a single mouse tumor model (TUBO/HER2+) using BALB/c mice, which may not represent the heterogeneity of human breast cancers. Manufacturing complexity of immunoliposomes with dual surface-conjugated proteins presents scalability challenges. The P5 peptide represents only one epitope of HER2, and immune escape through antigen loss is possible. Long-term immune memory and resistance to tumor rechallenge were not fully characterized. The study did not compare against existing HER2-targeted therapies like trastuzumab."},{"rthcId":"RPEP-05621","title":"A New Approach Against Some Oral Pathogenic Bacteria Using a Chimeric Antimicrobial Peptide Derived from the Camel Milk; Lactoferrampin - Lactoferricin Chimer.","authors":"Mohammadipour, Hamideh Sadat; Akbari, Majid; Tanhaeian, Abbas; Pourgonabadi, Solmaz; Sekandari, Salehe; Karimian, Elnaz","year":2021,"journal":"Current drug discovery technologies, 18(6), e130921187870","doi":"10.2174/1570163817999201111193507","pmid":"33183206","tags":["antimicrobial-peptides","lactoferrin"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"LFA-LFC chimeric peptide from camel lactoferrin was more effective than chlorhexidine against S. mutans and S. salivarius with good biocompatibility.","whyItMatters":"Antimicrobial resistance is growing. Natural peptide alternatives to chemical mouthwashes could prevent dental infections more safely.","specificNumbers":"MIC 1.22 μg/mL (S. salivarius); MBC 1.256 μg/mL (S. mutans); >50% cell viability; better than 0.2% chlorhexidine for streptococci","methodology":"Microbroth dilution antimicrobial testing against 4 oral bacteria. MTT cytotoxicity assay on human gingival fibroblasts. Compared with 0.2% chlorhexidine.","limitations":"In vitro testing only. Less effective against E. faecalis. Real-world oral environment is more complex. Formulation into a mouthwash not tested."},{"rthcId":"RPEP-05622","title":"Immunomodulation of Antimicrobial Peptides Expression in the Gastrointestinal Tract by Probiotics in Response to Stimulation by Salmonella minnesota Lipopolysaccharides.","authors":"Mohammed, Elsayed S I; Radey, Rasha","year":2021,"journal":"Probiotics and antimicrobial proteins, 13(4), 1157-1172","doi":"10.1007/s12602-021-09746-y","pmid":"33649897","tags":["defensins","antimicrobial-peptides"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Probiotic-feeding enhanced avian beta-defensin expression in chicken gut tissues in response to Salmonella LPS, without affecting cytokine levels.","whyItMatters":"Probiotics that boost natural antimicrobial defenses could reduce antibiotic use in poultry farming and improve food safety.","specificNumbers":"0.4% probiotics; 7 days; 1 or 100 μg LPS; 7-8 AvBDs per tissue; AvBD12 increased; 2-6 AvBDs enhanced; n=5-6/group","methodology":"Chicken study. Chicks fed 0.4% probiotics for 7 days then challenged with Salmonella minnesota LPS. Measured AvBD and cytokine expression in proventriculus and cecum at 5 hours post-challenge.","limitations":"Chicken model. Short-term LPS challenge (5 hours). Small group sizes (n=5-6). Specific probiotic strains not detailed in abstract."},{"rthcId":"RPEP-05623","title":"Weight-reducing, lipid-lowering and antidiabetic activities of a novel arginine vasopressin analogue acting at the V1a and V1b receptors in high-fat-fed mice.","authors":"Mohan, Shruti; Flatt, Peter R; Irwin, Nigel; Moffett, R Charlotte","year":2021,"journal":"Diabetes, obesity & metabolism, 23(10), 2215-2225","doi":"10.1111/dom.14462","pmid":"34105240","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05624","title":"Expression of acid cleavable Asp-Pro linked multimeric AFP peptide in E. coli.","authors":"Mollaev, Murad; Zabolotskii, Artur; Gorokhovets, Neonila; Nikolskaya, Elena; Sokol, Maria; Tsedilin, Andrey; Mollaeva, Mariia; Chirkina, Margarita; Kuvaev, Timofey; Pshenichnikova, Anna; Yabbarov, Nikita","year":2021,"journal":"Journal, genetic engineering & biotechnology, 19(1), 155","doi":"10.1186/s43141-021-00265-5","pmid":"34648110","tags":["peptide-drug-design"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"AFP receptor-binding peptide pentamer gave highest stable expression; formic acid hydrolyzed all Asp-Pro bonds at 100% efficiency; single HPLC step purified the product.","whyItMatters":"Cost-effective peptide production is crucial for therapeutic development. This method avoids expensive enzymes and chemical synthesis.","specificNumbers":"Pentamer optimal; 10 Asp-Pro bonds; 100% formic acid hydrolysis; single RP-HPLC purification; side products: formyl-Pro, formyl-Tyr, formyl-Lys","methodology":"Recombinant expression in E. coli with optimized pentamer design. Asp-Pro acid-cleavable linkers. Formic acid hydrolysis. Semi-preparative RP-HPLC purification.","limitations":"Optimized for one specific peptide. Formic acid can cause side modifications (formylation). May not work well for peptides with many hydroxyl or amino groups."},{"rthcId":"RPEP-05625","title":"The connexin 43 carboxyl terminal mimetic peptide αCT1 prompts differentiation of a collagen scar matrix in humans resembling unwounded skin.","authors":"Montgomery, Jade; Richardson, William J; Marsh, Spencer; Rhett, J Matthew; Bustos, Francis; Degen, Katherine; Ghatnekar, Gautam S; Grek, Christina L; Jourdan, L Jane; Holmes, Jeffrey W; Gourdie, Robert G","year":2021,"journal":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 35(8), e21762","doi":"10.1096/fj.202001881R","pmid":"34246197","tags":["peptide-drug-design","wound-healing"],"studyType":"clinical trial","evidenceStrength":"strong","keyFinding":"αCT1-treated scars showed significantly less collagen fiber alignment compared to vehicle-control treated wounds within the same patient at 29 days post-wounding — a pattern resembling unwounded skin rather than typical scar tissue.\n\nThe mechanism was traced to αCT1 causing decreased directionality of fibroblast movement during wound closure, which was demonstrated in both mouse and human fibroblast scratch wound assays. An agent-based computational model parameterized with the motility data successfully predicted the collagen alignment patterns observed in human and animal experiments. Phase II clinical trials had previously reported 47% improvement in scar appearance at 9 months post-surgery.","whyItMatters":"Scarring is a major clinical problem affecting tens of millions of people annually after surgeries and injuries. Current scar treatments are largely limited to silicone sheets and steroid injections with modest efficacy. A peptide that fundamentally changes how collagen is deposited during healing — making scars structurally resemble normal skin — represents a mechanistically novel approach with demonstrated clinical benefit.","specificNumbers":"47% scar improvement (Phase II, 9mo); less collagen alignment; faster closure; decreased directionality; targets Cx43 and ZO-1","methodology":"Multi-level investigation combining: (1) Phase I clinical trial biopsies comparing αCT1 vs. vehicle-treated wounds within the same patient at 29 days; (2) animal model replication in Sprague-Dawley rats and IAF hairless guinea pigs; (3) in vitro scratch wound assays with NIH 3T3 mouse fibroblasts and primary human dermal fibroblasts; (4) agent-based computational modeling to predict collagen organization from fibroblast motility data.","limitations":"Phase I biopsies were taken at 29 days, which captures early scar remodeling but not the full maturation process. Clinical sample sizes were small. Animal models, while confirmatory, do not perfectly replicate human scarring biology. The computational model makes simplifying assumptions about fibroblast behavior. Long-term collagen remodeling dynamics were not fully characterized."},{"rthcId":"RPEP-05626","title":"Pituitary adenylate cyclase-activating polypeptide/vasoactive intestinal peptide (Part 2): biology and clinical importance in central nervous system and inflammatory disorders.","authors":"Moody, Terry W; Jensen, Robert T","year":2021,"journal":"Current opinion in endocrinology, diabetes, and obesity, 28(2), 206-213","doi":"10.1097/MED.0000000000000621","pmid":"33481421","tags":["vip-peptide","pacap","neuropeptides"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"PACAP plays an important role in the pathogenesis of headaches (particularly migraine), post-traumatic stress disorder, and drug/alcohol/smoking addiction. VIP has demonstrated therapeutic effects in autoimmune and inflammatory disorders, especially rheumatoid arthritis. The development of specific drugs targeting this system — including monoclonal antibodies against VIP and PACAP — has advanced to therapeutic trials in some cases.","whyItMatters":"The success of CGRP-targeting antibodies for migraine proved that neuropeptide-based therapies can transform treatment of neurological conditions. VIP and PACAP represent the next frontier — a related neuropeptide system that appears to be involved not just in migraine but also in PTSD, addiction, and autoimmune diseases. If anti-VIP/PACAP drugs follow the trajectory of anti-CGRP drugs, they could provide new treatment options for millions of patients with these difficult-to-treat conditions.","specificNumbers":"PACAP: migraine, PTSD, addiction; VIP: rheumatoid arthritis; new: anti-VIP/PACAP monoclonal antibodies in development","methodology":"This is a narrative review (Part 2 of a series) discussing recent advances in understanding VIP/PACAP receptor biology in central nervous system and inflammatory disorders. The authors synthesize findings from basic science and clinical research on these neuropeptides.","limitations":"This is a narrative review, not a systematic review or meta-analysis, so the evidence selection may not be comprehensive. Many of the associations described are at the basic science level, and clinical trial data for anti-PACAP drugs remain limited. The mechanisms by which VIP/PACAP contribute to conditions like PTSD and addiction are not yet fully understood. The review does not provide quantitative outcome data."},{"rthcId":"RPEP-05627","title":"ERK and mTORC1 Inhibitors Enhance the Anti-Cancer Capacity of the Octpep-1 Venom-Derived Peptide in Melanoma BRAF(V600E) Mutations.","authors":"Moral-Sanz, Javier; Fernandez-Rojo, Manuel A; Potriquet, Jeremy; Mukhopadhyay, Pamela; Brust, Andreas; Wilhelm, Patrick; Smallwood, Taylor B; Clark, Richard J; Fry, Bryan G; Alewood, Paul F; Waddell, Nicola; Miles, John J; Mulvenna, Jason P; Ikonomopoulou, Maria P","year":2021,"journal":"Toxins, 13(2)","doi":"10.3390/toxins13020146","pmid":"33672955","tags":["venom-peptides","peptide-drug-design"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Octpep-1 targets PI3K/AKT/mTOR in BRAF V600E melanoma and synergizes with ERK and mTOR inhibitors for enhanced cytotoxicity.","whyItMatters":"Drug resistance to BRAF/MEK inhibitors is a major problem in melanoma. Venom-derived peptides targeting different pathways could overcome resistance.","specificNumbers":"Octpep-1 from O. kaurna; PI3K/AKT/mTOR pathway; combined with rapamycin and LY3214996; reduced glycolysis + respiration; perinuclear distribution","methodology":"Cell-based study using MM96L BRAF V600E melanoma cells. Fluorescence microscopy, proteomics, RNAseq, metabolic analysis. Combination testing with rapamycin and LY3214996.","limitations":"Cell culture study only. No in vivo tumor data. Single melanoma cell line. Peptide pharmacokinetics unknown."},{"rthcId":"RPEP-05628","title":"Efficacy of Intranodal Neoantigen Peptide-pulsed Dendritic Cell Vaccine Monotherapy in Patients With Advanced Solid Tumors: A Retrospective Analysis.","authors":"Morisaki, Takashi; Morisaki, Takafumi; Kubo, Makoto; Onishi, Hideya; Hirano, Tatsuya; Morisaki, Shinji; Eto, Masatoshi; Monji, Keisuke; Takeuchi, Ario; Nakagawa, Shinichiro; Tanaka, Hiroto; Koya, Norihiro; Umebayashi, Masayo; Tsujimura, Kenta; Yew, Poh Yin; Yoshimura, Sachiko; Kiyotani, Kazuma; Nakamura, Yusuke","year":2021,"journal":"Anticancer research, 41(8), 4101-4115","doi":"10.21873/anticanres.15213","pmid":"34281881","tags":["peptide-drug-design","immune-function"],"studyType":"clinical trial","evidenceStrength":"preliminary","keyFinding":"Intranodal neoantigen DC vaccination showed clinical responses in some advanced cancer patients, with response dependent on immune activation rather than neoantigen number.","whyItMatters":"Personalized cancer vaccines could help patients who have run out of other options. Intranodal delivery may improve immune responses.","specificNumbers":"N=17; intranodal ultrasound-guided injection; ELISpot monitoring; response dependent on immune activation, not neoantigen number","methodology":"Retrospective analysis of 17 patients with treatment-resistant advanced cancers. Whole exome sequencing for neoantigen prediction. Peptide-pulsed autologous DCs injected into lymph nodes via ultrasound. ELISpot immune monitoring.","limitations":"Retrospective analysis. Small sample (N=17). No control group. Heterogeneous cancer types. Not all patients responded."},{"rthcId":"RPEP-05629","title":"Intranodal Administration of Neoantigen Peptide-loaded Dendritic Cell Vaccine Elicits Epitope-specific T Cell Responses and Clinical Effects in a Patient with Chemorefractory Ovarian Cancer with Malignant Ascites.","authors":"Morisaki, Takashi; Hikichi, Tetsuro; Onishi, Hideya; Morisaki, Takafumi; Kubo, Makoto; Hirano, Tatsuya; Yoshimura, Sachiko; Kiyotani, Kazuma; Nakamura, Yusuke","year":2021,"journal":"Immunological investigations, 50(5), 562-579","doi":"10.1080/08820139.2020.1778721","pmid":"32660279","tags":["peptide-drug-design","immune-function"],"studyType":"clinical trial","evidenceStrength":"preliminary","keyFinding":"After four rounds of intranodal vaccination with neoantigen peptide-loaded dendritic cells, the patient experienced: remarkable decline in CA-125 levels (ovarian cancer marker), decreased tumor cells in malignant ascites, and improvement in tumor-related symptoms including respiratory discomfort — all without adverse reactions.\n\nImmunologically, the vaccine generated a detectable T cell response against an HLA-A2402-restricted neoantigen peptide derived from mutated PPM1F protein, confirmed by IFN-γ ELISPOT assay. Critically, neoantigen-specific T cell receptors (TCRs) were detected in tumor-infiltrating lymphocytes post-vaccination, demonstrating the vaccine successfully directed immune cells into the tumor.","whyItMatters":"Chemotherapy-resistant ovarian cancer has very few treatment options and is often fatal. This case demonstrates that personalized neoantigen peptide vaccines can produce both meaningful clinical improvements and measurable immune responses even in heavily pre-treated patients. The detection of neoantigen-specific T cells within the tumor is particularly encouraging, as it shows the vaccine is directing immune cells to where they're needed most.","specificNumbers":"1 patient; 4 neoantigen peptides; 4 vaccine rounds; CA-125 declined; ascites cells decreased; HLA-A2402 restricted PPM1F neoantigen; TCRs in tumor","methodology":"This is a single-patient case report. Neoantigens were identified using an immunogenomic pipeline (whole exome sequencing). Four neoantigen peptides were selected and loaded onto the patient's autologous dendritic cells. The vaccine was administered via ultrasound-guided intranodal injection over four rounds. Clinical response was monitored by CA-125 levels and ascites analysis. Immune response was assessed by IFN-γ ELISPOT assay on peripheral blood lymphocytes and TCR analysis of tumor-infiltrating lymphocytes.","limitations":"This is a single case report, which cannot prove causation — spontaneous disease fluctuations in ovarian cancer are possible. No control group for comparison. Long-term outcomes are not reported. The immunogenomic pipeline's peptide selection success rate (1 of 4 peptides generated detectable responses) suggests room for improvement in neoantigen prediction. Generalizability to other patients is unknown."},{"rthcId":"RPEP-05630","title":"Thymosin β4 protects against aortic aneurysm via endocytic regulation of growth factor signaling.","authors":"Munshaw, Sonali; Bruche, Susann; Redpath, Andia N; Jones, Alisha; Patel, Jyoti; Dubé, Karina N; Lee, Regent; Hester, Svenja S; Davies, Rachel; Neal, Giles; Handa, Ashok; Sattler, Michael; Fischer, Roman; Channon, Keith M; Smart, Nicola","year":2021,"journal":"The Journal of clinical investigation, 131(10)","doi":"10.1172/JCI127884","pmid":"33784254","tags":["thymosin-beta-4","cardiovascular-health"],"studyType":"animal study","evidenceStrength":"strong","keyFinding":"Tβ4 regulates LRP1-mediated endocytosis of PDGFR-β to maintain vascular stability. Tβ4-null mice develop aortic aneurysms rescuable by imatinib.","whyItMatters":"LRP1 variants are linked to aortic aneurysm risk in humans. Understanding how Tβ4 regulates this system could lead to new prevention strategies.","specificNumbers":"Tβ4-null: VSMC + elastin defects; enhanced PDGFR-β signaling; increased recycling, reduced lysosomal targeting of LRP1-PDGFR-β; imatinib rescue","methodology":"Mouse genetic study (Tβ4-null mice). Angiotensin II-induced aneurysm model. In vitro endocytosis and signaling studies. Imatinib rescue experiment.","limitations":"Mouse model. Angiotensin II-induced aneurysm may not fully represent human disease. Imatinib has significant side effects for chronic use."},{"rthcId":"RPEP-05631","title":"Peptide-Based Antiviral Drugs.","authors":"Murugan, N Arul; Raja, K Muruga Poopathi; Saraswathi, N T","year":2021,"journal":"Advances in experimental medicine and biology, 1322, 261-284","doi":"10.1007/978-981-16-0267-2_10","pmid":"34258744","tags":["peptide-drug-design","antimicrobial-peptides"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"60+ FDA-approved peptide drugs with 150+ in clinical trials. Antiviral peptides offer high specificity but face stability and delivery challenges addressable by chemical modification.","whyItMatters":"New antiviral drugs are always needed. Peptides offer a different approach from traditional small molecules with potentially better specificity.","specificNumbers":"60+ FDA approved; 150+ in clinical trials; since 1920; challenges: serum stability, oral BA, permeability; addressable by chemical modification","methodology":"Book chapter reviewing antiviral peptide drugs, their mechanisms, advantages, disadvantages, and comparison with small molecules.","limitations":"Review/book chapter. Broad overview rather than deep analysis of specific antiviral peptides. Field is rapidly evolving."},{"rthcId":"RPEP-05632","title":"LEAP2 Impairs the Capability of the Growth Hormone Secretagogue Receptor to Regulate the Dopamine 2 Receptor Signaling.","authors":"Mustafá, Emilio R; Cordisco González, Santiago; Damian, Marjorie; Cantel, Sonia; Denoyelle, Severine; Wagner, Renaud; Schiöth, Helgi B; Fehrentz, Jean-Alain; Banères, Jean-Louis; Perelló, Mario; Raingo, Jesica","year":2021,"journal":"Frontiers in pharmacology, 12, 712437","doi":"10.3389/fphar.2021.712437","pmid":"34447311","tags":["ghrelin","ghsr-receptor","antimicrobial-peptides"],"studyType":"mechanistic","evidenceStrength":"moderate","keyFinding":"LEAP-2 N-terminal region stabilizes GHSR in an inactive conformation, dissociating it from Gq and reversing its modulation of D2R-Gi signaling.","whyItMatters":"GHSR's interaction with the dopamine system links appetite to reward. Understanding how LEAP-2 controls this could lead to new treatments for obesity and addiction.","specificNumbers":"Blocks: ghrelin-evoked, constitutive, D2R modulation; N-terminal LEAP-2; CaV2.2 currents; FRET: inactive GHSR dissociates from Gq; reverses D2R-Gi","methodology":"Heterologous expression with patch-clamp electrophysiology measuring CaV2.2 currents. Purified labeled receptors in lipid nanodiscs with FRET measurements.","limitations":"Heterologous expression system may not fully represent neurons. Lipid nanodisc studies are simplified models. In vivo behavioral validation not included."},{"rthcId":"RPEP-05633","title":"Trends in peptide drug discovery.","authors":"Muttenthaler, Markus; King, Glenn F; Adams, David J; Alewood, Paul F","year":2021,"journal":"Nature reviews. Drug discovery, 20(4), 309-325","doi":"10.1038/s41573-020-00135-8","pmid":"33536635","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Over 80 peptide drugs have reached the market since insulin's introduction, covering a remarkably diverse range of therapeutic areas. The review identifies several key waves of peptide drug development:\n\n1) Early hormone-based drugs: insulin, oxytocin, vasopressin, ACTH\n2) Medicinal chemistry era: rational design and chemical modifications to improve stability and selectivity\n3) Nature-derived peptides: venom-derived drugs (ziconotide from cone snails, exenatide from Gila monster), natural product-inspired designs\n4) Molecular biology advances: recombinant production, phage display, mRNA display\n5) Emerging strategies: integrated venomics (systematic venom mining), peptide-display libraries, AI-guided design\n\nThe authors emphasize that lessons from earlier approaches remain highly relevant, and that peptide drugs occupy a unique pharmaceutical 'sweet spot' between small molecules and biologics.","whyItMatters":"Peptide drugs represent one of the fastest-growing segments of the pharmaceutical industry, with blockbusters like semaglutide (Ozempic/Wegovy) and tirzepatide (Mounjaro/Zepbound) generating tens of billions in revenue. This authoritative review explains how we got here and where the field is headed. For anyone interested in peptide science — researchers, investors, patients, or clinicians — this is the definitive big-picture overview of the field's trajectory.","specificNumbers":"","methodology":"This is a Perspective article in Nature Reviews Drug Discovery — a high-impact review format that combines comprehensive literature analysis with expert opinion and forward-looking strategic assessment. The authors, who are leading peptide scientists, surveyed the entire history of peptide drug development, analyzed current trends and pipelines, and identified emerging opportunities and challenges.","limitations":"As a Perspective rather than a systematic review, the coverage reflects the authors' expertise and interests. The review was published in 2021, so it does not cover the most recent developments including the explosive growth of GLP-1 drugs for obesity, tirzepatide's approval, or advances in AI-guided peptide design. The pharmaceutical pipeline information is frozen at the time of writing. The review focuses primarily on approved drugs and advanced clinical candidates, with less coverage of very early-stage research."},{"rthcId":"RPEP-05634","title":"Diabetes Insipidus: Pathogenesis, Diagnosis, and Clinical Management.","authors":"Mutter, Cody M; Smith, Trevor; Menze, Olivia; Zakharia, Mariah; Nguyen, Hoang","year":2021,"journal":"Cureus, 13(2), e13523","doi":"10.7759/cureus.13523","pmid":"33786230","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05635","title":"Metaplastic contribution of neuropeptide Y receptors to spatial memory acquisition.","authors":"Méndez-Couz, Marta; Manahan-Vaughan, Denise; Silva, Ana Paula; González-Pardo, Héctor; Arias, Jorge Luis; Conejo, Nélida María","year":2021,"journal":"Behavioural brain research, 396, 112864","doi":"10.1016/j.bbr.2020.112864","pmid":"32827566","tags":["neuropeptide-y","neuropeptides"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"Hippocampal Y2R blockade improved spatial memory, and learning dynamically changed Y2R/Y1R expression in hippocampus and prefrontal cortex.","whyItMatters":"Understanding how neuropeptides regulate memory could lead to treatments for memory disorders and age-related cognitive decline.","specificNumbers":"Y2R antagonism improved spatial reference memory; Y2R up in hippocampus, down in PFC after training; Y1R opposite pattern; no anxiety/motor changes","methodology":"Rat study with dorsal intrahippocampal injection of Y2R antagonist. Morris water maze for spatial memory. Measured Y2R and Y1R expression in hippocampus and prefrontal cortex after training.","limitations":"Rat model. Direct hippocampal injection is not clinically practical. Results may not translate to human memory processes."},{"rthcId":"RPEP-05636","title":"Potential Molecular Targets for Treating Neuropathic Orofacial Pain Based on Current Findings in Animal Models.","authors":"Nagakura, Yukinori; Nagaoka, Shogo; Kurose, Takahiro","year":2021,"journal":"International journal of molecular sciences, 22(12)","doi":"10.3390/ijms22126406","pmid":"34203854","tags":["cgrp","neuropeptides"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"CGRP receptor antagonists emerge as the most promising molecular target for neuropathic orofacial pain, with sufficient safety and mechanistic data for clinical translation.","whyItMatters":"Chronic face pain severely affects quality of life and has few effective treatments. Identifying validated molecular targets could lead to new therapies.","specificNumbers":"Models: PTNP (nerve trauma) and PTN (root compression); targets: CGRP, inflammation, ectopic discharges, neuron-glia interactions","methodology":"Narrative review of animal models of post-traumatic trigeminal neuropathic pain (PTNP) and primary trigeminal neuralgia (PTN), and therapeutic candidates identified therein.","limitations":"Review of animal models. Pain mechanisms in animals may not perfectly represent human neuropathic pain. Clinical translation is not guaranteed."},{"rthcId":"RPEP-05637","title":"Identification of Neoantigens in Two Murine Gastric Cancer Cell Lines Leading to the Neoantigen-Based Immunotherapy.","authors":"Nagaoka, Koji; Sun, Changbo; Kobayashi, Yukari; Kanaseki, Takayuki; Tokita, Serina; Komatsu, Toshihiro; Maejima, Kazuhiro; Futami, Junichiro; Nomura, Sachiyo; Udaka, Keiko; Nakagawa, Hidewaki; Torigoe, Toshihiko; Kakimi, Kazuhiro","year":2021,"journal":"Cancers, 14(1)","doi":"10.3390/cancers14010106","pmid":"35008270","tags":["peptide-drug-design","immune-function"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"Mutated Cdt1 was the dominant neoantigen in mouse gastric cancer. DC vaccination and T cell transfer targeting it controlled tumor growth.","whyItMatters":"Well-characterized preclinical models are essential for developing cancer immunotherapies. This provides a model for testing gastric cancer vaccines.","specificNumbers":"YTN2: 2 neoantigens; YTN16: 3 neoantigens; 1 MHC-I presented (mCdt1); DC vaccine + T cell transfer controlled YTN16; anti-CTLA-4: 4/5 eradicated","methodology":"Whole exome + RNA sequencing of YTN2 and YTN16 mouse gastric cancer lines. MHC ligandome analysis. DC vaccine and adoptive T cell transfer experiments. Anti-checkpoint antibody testing.","limitations":"Mouse model. Low neoantigen numbers may not represent human gastric cancer diversity. Single dominant neoantigen may be specific to these cell lines."},{"rthcId":"RPEP-05638","title":"Role of Monoclonal Antibodies against Calcitonin Gene-Related Peptide (CGRP) in Episodic Migraine Prevention: Where Do We Stand Today?","authors":"Nagaraj, Karthik; Vandenbussche, Nicolas; Goadsby, Peter J","year":2021,"journal":"Neurology India, 69(Supplement), S59-S66","doi":"10.4103/0028-3886.315997","pmid":"34003149","tags":["cgrp","neuropeptides"],"studyType":"review","evidenceStrength":"strong","keyFinding":"All four anti-CGRP mAbs are effective for episodic and chronic migraine with placebo-comparable side effects, including in patients who failed prior preventives.","whyItMatters":"Migraine is the sixth most common disorder worldwide. Having four targeted preventive options with excellent tolerability transforms patient care.","specificNumbers":"4 mAbs: erenumab, fremanezumab, galcanezumab, eptinezumab; all Phase 3 positive; AEs ≈ placebo; effective in prior failures","methodology":"Literature review of Phase 2 and 3 clinical trials of erenumab, fremanezumab, galcanezumab, and eptinezumab for episodic migraine.","limitations":"Review without quantitative meta-analysis. Long-term safety data still accumulating. Cost and access remain barriers in many countries."},{"rthcId":"RPEP-05639","title":"Intranasal Neuropeptide Y as a Potential Therapeutic for Depressive Behavior in the Rodent Single Prolonged Stress Model in Females.","authors":"Nahvi, Roxanna J; Tanelian, Arax; Nwokafor, Chiso; Hollander, Callie M; Peacock, Lauren; Sabban, Esther L","year":2021,"journal":"Frontiers in behavioral neuroscience, 15, 705579","doi":"10.3389/fnbeh.2021.705579","pmid":"34566592","tags":["neuropeptide-y","neuropeptides"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"Female rats needed 1,200 μg intranasal NPY (4x male dose) to prevent SPS-induced depression. Combining 600 μg NPY + DPP4 inhibitor was equally effective.","whyItMatters":"PTSD and depression disproportionately affect women. Understanding sex-specific dosing of neuropeptide therapies is essential for effective treatment.","specificNumbers":"1,200 μg effective (4x male 300 μg); 600 μg alone ineffective; 600 μg + omarigliptin effective; prevented FST depression; tested at 19 days post-SPS","methodology":"Sprague-Dawley female rats. SPS model. Multiple NPY doses tested intranasally after SPS. Behavioral testing at 19 days: forced swim, elevated plus maze, social interaction. DPP4 inhibitor combination tested.","limitations":"Rat model. SPS may not fully replicate human PTSD. Only one behavioral timepoint tested. Intranasal delivery in rats differs from humans."},{"rthcId":"RPEP-05640","title":"Identification of mouse helper epitopes for WT1-specific CD4+ T cells.","authors":"Nakajima, Hiroko; Nakata, Jun; Imafuku, Kanako; Hayashibara, Hiromu; Isokawa, Kazuki; Udaka, Keiko; Fujiki, Fumihiro; Morimoto, Soyoko; Hasegawa, Kana; Hosen, Naoki; Hashii, Yoshiko; Nishida, Sumiyuki; Tsuboi, Akihiro; Oka, Yoshihiro; Oji, Yusuke; Sogo, Shinji; Sugiyama, Haruo","year":2021,"journal":"Cancer immunology, immunotherapy : CII, 70(11), 3323-3335","doi":"10.1007/s00262-021-03003-5","pmid":"34272593","tags":["peptide-drug-design","immune-function"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"Three novel WT1 Th peptides strongly enhanced CTL induction, maintenance, and tumor rejection when co-immunized with WT1 CTL peptide in mice.","whyItMatters":"WT1 is overexpressed in many cancers. Better vaccines incorporating helper peptides could improve cancer immunotherapy outcomes.","specificNumbers":"3 Th peptides: WT135-52, WT186-102, WT1294-312; enhanced CTL induction + maintenance; CD44+CD62L- effector memory; improved tumor rejection","methodology":"Mouse immunization study. Identified WT135-52, WT186-102, and WT1294-312 Th peptides. Co-immunization with WT1 CTL peptide. Tumor challenge with WT1-expressing cells. T cell phenotyping.","limitations":"Mouse model. WT1-specific responses in humans may differ. Specific peptides are MHC-restricted and may need human counterparts identified."},{"rthcId":"RPEP-05641","title":"GLP-1 receptor agonists in the treatment of type 2 diabetes - state-of-the-art.","authors":"Nauck, Michael A; Quast, Daniel R; Wefers, Jakob; Meier, Juris J","year":2021,"journal":"Molecular metabolism, 46, 101102","doi":"10.1016/j.molmet.2020.101102","pmid":"33068776","tags":[],"studyType":"review","evidenceStrength":"strong","keyFinding":"This comprehensive review covers the entire GLP-1 receptor agonist class for type 2 diabetes, documenting their evolution from twice-daily exenatide (2005) to once-weekly and oral formulations. Key conclusions: GLP-1 RAs reduce HbA1c and body weight without intrinsic hypoglycemia risk, are now recommended as the preferred first injectable therapy before insulin, and several cardiovascular outcome trials have shown they prevent heart attacks, strokes, and associated mortality in patients with atherosclerotic disease. Semaglutide emerged as the most effective for both glucose lowering and weight loss. Novel indications being explored include type 1 diabetes, neurodegenerative diseases, and psoriasis.","whyItMatters":"This review captures a pivotal moment in GLP-1 RA history — the class had just been elevated in treatment guidelines to preferred first injectable therapy over insulin, cardiovascular benefits were confirmed across multiple large trials, and oral semaglutide had just arrived. It provides the authoritative summary of how GLP-1 RAs transformed diabetes treatment within 15 years of their introduction.","specificNumbers":"First approved 2005 · Dosing ranges: twice daily to once weekly to daily oral · CV outcome trials from 2016 onward · Semaglutide: most effective for HbA1c + weight","methodology":"Narrative review summarizing clinical trial data, mechanisms of action, pharmacological development, cardiovascular outcome studies, and treatment guidelines for the GLP-1 receptor agonist class.","limitations":"This is a narrative review, not a systematic review or meta-analysis, so it does not use formal methodology for evidence synthesis. Published in early 2021, it predates tirzepatide approval and the explosion of GLP-1 use for obesity as a primary indication."},{"rthcId":"RPEP-05642","title":"The evolving story of incretins (GIP and GLP-1) in metabolic and cardiovascular disease: A pathophysiological update.","authors":"Nauck, Michael A; Quast, Daniel R; Wefers, Jakob; Pfeiffer, Andreas F H","year":2021,"journal":"Diabetes, obesity & metabolism, 23 Suppl 3, 5-29","doi":"10.1111/dom.14496","pmid":"34310013","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05643","title":"Immunopeptidomics-Guided Warehouse Design for Peptide-Based Immunotherapy in Chronic Lymphocytic Leukemia.","authors":"Nelde, Annika; Maringer, Yacine; Bilich, Tatjana; Salih, Helmut R; Roerden, Malte; Heitmann, Jonas S; Marcu, Ana; Bauer, Jens; Neidert, Marian C; Denzlinger, Claudio; Illerhaus, Gerald; Aulitzky, Walter Erich; Rammensee, Hans-Georg; Walz, Juliane S","year":2021,"journal":"Frontiers in immunology, 12, 705974","doi":"10.3389/fimmu.2021.705974","pmid":"34305947","tags":["cancer","peptide-design","immune-function"],"studyType":"translational","evidenceStrength":"preliminary","keyFinding":"The team used mass spectrometry to compare protein fragments displayed on CLL cells versus normal tissue. They found several tumor-associated fragments that appeared often across many CLL patients.\n\nThese fragments triggered immune responses from both existing and newly created T cells in CLL patients and healthy volunteers. The researchers packaged these peptides into a pre-made warehouse, so doctors could quickly assemble a personalized multi-peptide vaccine for each patient without starting from scratch.\n\nThis matters because CLL has very few mutations, making it hard to find unique cancer targets. The warehouse approach sidesteps this problem by using non-mutated but tumor-associated peptides that still provoke an immune response.","whyItMatters":"Most peptide cancer vaccines require expensive, time-consuming custom design for each patient. This study shows a way to pre-build a library of peptides that work across many patients. For cancers like CLL that have few mutations, this warehouse model could make peptide vaccines practical and affordable.","specificNumbers":"Clinical trial NCT04688385 launched; T cell responses confirmed in CLL patients and healthy volunteers","methodology":"Researchers collected CLL samples from patients and compared them to a database of normal tissue samples. They used mass spectrometry to identify protein fragments (immunopeptidome) displayed on cancer cell surfaces. They then tested whether these fragments could activate T cells from both CLL patients and healthy people. A phase I clinical trial (NCT04688385) was launched using the resulting peptide warehouse.","limitations":"This study describes the workflow and initial immune responses but does not yet show whether the vaccines shrink tumors or extend survival. The clinical trial is still in early stages. The immune responses were measured in lab conditions, and real-world vaccine performance may differ. The sample size of CLL patients analyzed for immunopeptidome data was not large."},{"rthcId":"RPEP-05644","title":"A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis.","authors":"Newsome, Philip N; Buchholtz, Kristine; Cusi, Kenneth; Linder, Martin; Okanoue, Takeshi; Ratziu, Vlad; Sanyal, Arun J; Sejling, Anne-Sophie; Harrison, Stephen A","year":2021,"journal":"The New England journal of medicine, 384(12), 1113-1124","doi":"10.1056/NEJMoa2028395","pmid":"33185364","tags":["semaglutide","liver-disease","glp-1-agonists"],"studyType":"Randomized Controlled Trial (Phase 2)","evidenceStrength":"Strong","keyFinding":"In a 72-week trial published in the New England Journal of Medicine, semaglutide at 0.4 mg daily achieved NASH resolution (without worsening fibrosis) in 59% of patients, compared to 17% on placebo (P<0.001). This was confirmed by liver biopsy — the gold standard for assessing liver disease.\n\nHowever, semaglutide did not significantly improve fibrosis: 43% of the 0.4 mg group had fibrosis improvement versus 33% on placebo (P=0.48, not significant). Patients on the highest dose lost an average of 13% of their body weight compared to 1% on placebo. GI side effects were common — 42% experienced nausea and 15% had vomiting at the 0.4 mg dose. A small neoplasm signal was noted (3 malignancies in semaglutide groups vs. 0 on placebo), though no pattern was evident.","whyItMatters":"This was the first major RCT to test semaglutide specifically for NASH/MASH, published in the world's most prestigious medical journal. The 59% NASH resolution rate at 0.4 mg daily was striking — but the failure to significantly improve fibrosis is the critical limitation, because fibrosis stage is the strongest predictor of liver-related death. This result helped shape the field's understanding that GLP-1 drugs alone may not be enough for advanced liver disease, motivating combination approaches (like adding efruxifermin or resmetirom).","specificNumbers":"n=320 · 72 weeks · semaglutide 0.1, 0.2, 0.4 mg daily · NASH resolution: 59% vs 17% placebo (0.4 mg, P<.001) · fibrosis improvement: 43% vs 33% (P=.48, NS) · weight loss: 13% vs 1% · nausea: 42% vs 11% · vomiting: 15% vs 2%","methodology":"72-week, double-blind, placebo-controlled phase 2 trial. 320 patients with biopsy-confirmed NASH and fibrosis (F1-F3) were randomized 3:3:3:1:1:1 to semaglutide 0.1, 0.2, or 0.4 mg daily or corresponding placebo via subcutaneous injection. Primary endpoint: NASH resolution without fibrosis worsening, assessed by paired liver biopsies. Confirmatory secondary endpoint: improvement of at least one fibrosis stage without NASH worsening. Endpoint analyses for these outcomes were restricted to the 230 patients with F2-F3 fibrosis.","limitations":"Phase 2 trial with 320 patients — adequately powered for the primary endpoint but may be underpowered for fibrosis improvement detection. The semaglutide doses (0.1-0.4 mg daily) differ from the approved weight-loss dose (2.4 mg weekly as Wegovy), making direct comparisons with current clinical practice difficult. The 72-week duration may be insufficient to show fibrosis reversal, which is a slow process. The small neoplasm signal warrants monitoring in larger trials. Daily subcutaneous dosing is more burdensome than the once-weekly formulation used clinically."},{"rthcId":"RPEP-05645","title":"A Randomized, Double-blind, Placebo-controlled Clinical Study Investigating the Efficacy and Tolerability of a Peptide Serum Targeting Expression Lines.","authors":"Nguyen, Thu Q; Zahr, Alisar S; Kononov, Tatiana; Ablon, Glynis","year":2021,"journal":"The Journal of clinical and aesthetic dermatology, 14(5), 14-21","doi":null,"pmid":"34188744","tags":[],"studyType":"Randomized Controlled Trial","evidenceStrength":"Moderate-High","keyFinding":"A line-targeting peptide serum (LTPS) containing neuromodulating peptides significantly improved expression lines compared to placebo at all measured time points — as early as 15 minutes after first application and sustained through 12 weeks of twice-daily use.\n\nBoard-certified dermatologist evaluation confirmed the peptide serum outperformed placebo for both expression lines and overall skin health parameters at Weeks 4, 8, and 12. These clinical assessments were supported by objective imaging: VISIA photography and 3D PRIMOS CR wrinkle analysis both substantiated the serum's efficacy. The treatment was well tolerated with no reported safety concerns.","whyItMatters":"Expression lines are among the most common cosmetic concerns, and many people want alternatives to injectable neuromodulators like botulinum toxin. This study provides double-blind, placebo-controlled evidence that a topical peptide serum can meaningfully reduce wrinkles — offering a non-invasive option backed by clinical-grade imaging data rather than just subjective impressions.","specificNumbers":"n=55 · 12-week duration · Fitzpatrick Skin Types I–VI · Improvement seen at 15 minutes, Weeks 4, 8, and 12 · Statistically significant vs placebo at all time points","methodology":"Fifty-five women aged 35–60 with mild to moderate facial fine lines were randomized to apply either the peptide serum or a placebo serum twice daily for 12 weeks. The study was double-blind and IRB-approved. Short-term effects were assessed 15 minutes after the first application. Long-term results were evaluated at Weeks 4, 8, and 12 using dermatologist grading, self-assessment questionnaires, VISIA clinical photography, and 3D PRIMOS CR imaging for objective wrinkle measurement.","limitations":"The study included only 55 female subjects, limiting generalizability to men or larger populations. Specific numerical improvements (percentage reduction in wrinkle depth) were not reported in the abstract. The exact peptide composition of the serum was not disclosed, making it difficult to compare with other peptide products. The 12-week duration, while reasonable, does not address long-term durability of results after discontinuation."},{"rthcId":"RPEP-05646","title":"Transcriptome analysis of early stages of sorghum grain mold disease reveals defense regulators and metabolic pathways associated with resistance.","authors":"Nida, Habte; Lee, Sanghun; Li, Ying; Mengiste, Tesfaye","year":2021,"journal":"BMC genomics, 22(1), 295","doi":"10.1186/s12864-021-07609-y","pmid":"33888060","tags":["antimicrobial-peptides","peptide-design"],"studyType":"basic-research","evidenceStrength":"preliminary","keyFinding":"When researchers infected both resistant (RTx2911) and susceptible (RTx430) sorghum grains with a mix of fungal pathogens, the resistant strain activated over 1,000 defense-related genes. Two defensin genes, SbDFN7.1 and SbDFN7.2, stood out with much higher expression in the resistant grain.\n\nThese two defensin genes sit right next to each other on the genome and are read in opposite directions, likely sharing a single control switch (bidirectional promoter). The resistant strain also turned on genes for pattern recognition receptors (proteins that detect fungal invaders) and phytoalexins (chemical weapons against fungi).\n\nThe study also found genes that suppress defense responses (JAZ repressors), showing the plant carefully balances fighting infection with continuing to grow.","whyItMatters":"Sorghum grain mold causes major crop losses worldwide, and there are few effective treatments. Identifying the specific defensin genes and pathways behind natural resistance gives plant breeders concrete targets for developing mold-resistant sorghum varieties.","specificNumbers":"SbDFN7.1 and SbDFN7.2 defensin genes highly expressed in resistant RTx2911 vs susceptible RTx430","methodology":"Researchers inoculated developing grain kernels from two sorghum varieties with a mix of fungal species that mimic natural mold infection. They then compared the full set of active genes (transcriptome) between the resistant and susceptible strains to find which genes were turned on or off differently.","limitations":"This is a plant study with no human health component. The gene expression data shows correlation, not proof that these genes cause resistance. The study used a lab inoculation, which may not fully reflect field conditions. Functional validation (knocking out or overexpressing these genes) was not performed."},{"rthcId":"RPEP-05647","title":"A Review on the Efficacy and Safety of Oral Semaglutide.","authors":"Niman, Stephanie; Hardy, Jennifer; Goldfaden, Rebecca F; Reid, Jessica; Sheikh-Ali, Mae; Sutton, David; Choksi, Rushab","year":2021,"journal":"Drugs in R&D, 21(2), 133-148","doi":"10.1007/s40268-021-00341-8","pmid":"33772451","tags":["semaglutide","diabetes","oral-peptides","cardiovascular"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Oral semaglutide is the first GLP-1 receptor agonist (a gut hormone drug that controls blood sugar and appetite) available as a pill. In the PIONEER trials, it consistently lowered HbA1c (a measure of blood sugar control) and reduced body weight compared to placebo and several other diabetes drugs.\n\nThe drug uses an absorption enhancer called SNAC to get through the stomach lining, since peptides normally break down in the gut. Three other GLP-1 drugs (subcutaneous semaglutide, dulaglutide, and liraglutide) already have FDA approval for reducing heart attack and stroke risk in diabetic patients with heart disease.\n\nOral semaglutide showed signals of heart benefit in early data, but did not yet have an official FDA indication for cardiovascular protection. The SOUL trial was designed to answer that question definitively.","whyItMatters":"Most GLP-1 drugs require injections, which many patients avoid. Having a pill option removes that barrier and could lead to earlier treatment. If oral semaglutide also proves to protect the heart, it would be the first oral GLP-1 with that benefit.","specificNumbers":"Oral semaglutide tested at 3, 7, and 14 mg daily; PIONEER trial program; SOUL trial ongoing","methodology":"This is a narrative review summarizing data from the PIONEER trial program, which tested oral semaglutide at various doses against placebo and active comparators in patients with type 2 diabetes. The review covers efficacy for blood sugar control, weight loss, and cardiovascular outcomes.","limitations":"This is a review, not an original study. It summarizes existing trial data without new analysis. The cardiovascular benefit question was still unanswered at publication time. The review does not deeply compare oral semaglutide to newer agents like tirzepatide."},{"rthcId":"RPEP-05648","title":"Controlling Nucleopeptide Hydrogel Self-Assembly and Formation for Cell-Culture Scaffold Applications.","authors":"Noblett, Alexander David; Baek, Kiheon; Suggs, Laura J","year":2021,"journal":"ACS biomaterials science & engineering, 7(6), 2605-2614","doi":"10.1021/acsbiomaterials.0c01658","pmid":"33949850","tags":["peptide-design","peptide-delivery"],"studyType":"basic-research","evidenceStrength":"preliminary","keyFinding":"The team discovered that nucleopeptide self-assembly depends on the type of buffer and ions in the solution. Buffer pH and ion charge (especially divalent cations like calcium) control whether and how strongly the gel forms.\n\nAdding divalent cations increased the hydrogel stiffness by 10 times (one order of magnitude in storage modulus). This tunability is valuable because different tissues need scaffolds with different stiffness levels.\n\nFibroblasts (common connective tissue cells) survived and multiplied on the hydrogel surfaces, confirming the gels are safe for cell culture. The gelation happens at physiological pH and osmolarity, meaning no harsh chemicals are needed.","whyItMatters":"Many peptide hydrogels require harsh chemicals or extreme conditions to form, which kills cells. This system uses gentle, cell-compatible conditions, making it practical for tissue engineering. The ability to tune stiffness by adding salts gives researchers control over the scaffold properties.","specificNumbers":"10x increase in storage modulus with divalent cations; gelation at physiological pH and osmolarity","methodology":"Researchers synthesized short nucleopeptides and tested their self-assembly in various biological buffers and salt solutions. They measured gel stiffness (storage modulus) and used analytical and computational methods to understand how pH and salts affect the molecular structure. They then seeded fibroblasts on the hydrogel surfaces to test biocompatibility.","limitations":"Only fibroblasts were tested. Other cell types may respond differently. The study did not test the hydrogel in a living animal. Long-term stability and degradation rates were not fully characterized. The mechanical properties, while tunable, may not match all tissue types."},{"rthcId":"RPEP-05649","title":"Human Breast Milk Enhances Intestinal Mucosal Barrier Function and Innate Immunity in a Healthy Pediatric Human Enteroid Model.","authors":"Noel, Gaelle; In, Julie G; Lemme-Dumit, Jose M; DeVine, Lauren R; Cole, Robert N; Guerrerio, Anthony L; Campbell, James D; Kovbasnjuk, Olga; Pasetti, Marcela F","year":2021,"journal":"Frontiers in cell and developmental biology, 9, 685171","doi":"10.3389/fcell.2021.685171","pmid":"34327199","tags":["antimicrobial-peptides","immune-function","gut-healing"],"studyType":"basic-research","evidenceStrength":"preliminary","keyFinding":"Colostrum (early breast milk) applied to pediatric enteroids (lab-grown mini-intestines from human tissue) reduced ion permeability, meaning the gut barrier became tighter and harder for harmful substances to cross. It also increased the tight junction protein occludin, which acts like cellular glue.\n\nBreast milk increased production of alpha-defensin 5 (an antimicrobial peptide) by both goblet cells and Paneth cells. These are specialized gut cells that produce mucus and antimicrobial compounds to protect against infection.\n\nBreast milk also stopped the release of the pro-inflammatory signal GM-CSF from the cell surface and enabled the transport of maternal IgA (an antibody) across the gut lining via the pIgR receptor. Commercial infant formula did none of these things.\n\nProtein analysis revealed that breast milk activated pathways related to tissue remodeling and maintaining healthy gut function.","whyItMatters":"This study provides molecular evidence for why breastfeeding protects infants from gut infections. The specific finding that breast milk boosts alpha-defensin 5, a key antimicrobial peptide, and tightens the gut barrier gives concrete mechanisms behind long-observed health benefits.","specificNumbers":"Alpha-defensin 5 upregulated; occludin increased; GM-CSF release abolished; IgA transport via pIgR enabled","methodology":"Researchers created enteroid monolayers (flat sheets of mini-intestine cells) from pediatric human tissue. They applied breast milk colostrum or commercial infant formula to the surface and measured barrier function, antimicrobial peptide production, cytokine release, antibody transport, and protein changes.","limitations":"This is a lab model using enteroids, not a study in living infants. The enteroids approximate but do not fully replicate the complexity of an infant's gut. Only colostrum was tested, and breast milk composition changes over time. The study did not test how long these effects last or whether they prevent actual infections."},{"rthcId":"RPEP-05650","title":"Macropinocytosis-Inducible Extracellular Vesicles Modified with Antimicrobial Protein CAP18-Derived Cell-Penetrating Peptides for Efficient Intracellular Delivery.","authors":"Noguchi, Kosuke; Obuki, Momoko; Sumi, Haruka; Klußmann, Merlin; Morimoto, Kenta; Nakai, Shinya; Hashimoto, Takuya; Fujiwara, Daisuke; Fujii, Ikuo; Yuba, Eiji; Takatani-Nakase, Tomoka; Neundorf, Ines; Nakase, Ikuhiko","year":2021,"journal":"Molecular pharmaceutics, 18(9), 3290-3301","doi":"10.1021/acs.molpharmaceut.1c00244","pmid":"34365796","tags":["cell-penetrating","peptide-delivery","antimicrobial-peptides"],"studyType":"basic-research","evidenceStrength":"preliminary","keyFinding":"The dimerized (doubled) form of the CAP18-derived peptide, called (sC18)2, was easily attached to extracellular vesicle (EV) membranes when linked to a fat-loving molecule. Once attached, the peptide triggered macropinocytosis, a process where cells engulf large amounts of surrounding fluid and particles.\n\nThis dramatically increased how many EVs got inside target cells. The process depended on glycosaminoglycans (sugar chains on cell surfaces). The team showed this could deliver a functional toxin protein (saporin) that was loaded into the EVs by electroporation.\n\nThe saporin-loaded, peptide-modified EVs killed target cells, proving the cargo reached the inside of the cell and was biologically active.","whyItMatters":"Extracellular vesicles are promising drug delivery vehicles because cells naturally take them up. But uptake is often too low for therapeutic use. This peptide modification solves that problem by forcing cells to gulp in more EVs, opening the door to EV-based delivery of proteins, toxins, or other drugs.","specificNumbers":"(sC18)2 peptide modification; glycosaminoglycan-dependent macropinocytosis; saporin toxin delivery confirmed","methodology":"Researchers modified the (sC18)2 peptide with a hydrophobic (fat-loving) anchor so it would stick to EV membranes. They tested cellular uptake in multiple cell lines (CHO, HeLa, MCF-7). They loaded saporin toxin into EVs by electroporation and measured cell killing to confirm intracellular delivery. They also tested which uptake pathway was responsible using pathway-blocking experiments.","limitations":"All experiments were done in cell lines in the lab, not in animals or humans. The study did not test whether the peptide-modified EVs cause immune reactions in a living body. Long-term stability of the peptide coating was not assessed. Only one toxin payload was tested."},{"rthcId":"RPEP-05651","title":"Role of perivascular nerve and sensory neurotransmitter dysfunction in inflammatory bowel disease.","authors":"Norton, Charles E; Grunz-Borgmann, Elizabeth A; Hart, Marcia L; Jones, Benjamin W; Franklin, Craig L; Boerman, Erika M","year":2021,"journal":"American journal of physiology. Heart and circulatory physiology, 320(5), H1887-H1902","doi":"10.1152/ajpheart.00037.2021","pmid":"33710922","tags":["neuropeptides","gut-healing","inflammation"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"In mesenteric arteries (blood vessels feeding the gut) from mice with IBD, sensory nerve-driven blood vessel relaxation was severely impaired. Both CGRP and substance P levels released by nerves were reduced.\n\nBut the two peptides were affected differently. CGRP nerve density, receptor levels, and direct vessel-opening ability were preserved. Substance P nerve density was decreased but its receptor (NK1) was increased, and substance P's vessel-opening effect was impaired.\n\nThe key discovery: blocking NK1 receptors (substance P receptors) restored normal sensory vasodilation and even enhanced CGRP-mediated vessel opening. This means substance P signaling was actively interfering with CGRP's ability to open blood vessels.\n\nThe researchers propose that in IBD, abnormal substance P signaling blocks CGRP from maintaining healthy gut blood flow, contributing to intestinal damage.","whyItMatters":"IBD patients have impaired gut blood flow and higher cardiovascular risk, but the connection is poorly understood. This study identifies substance P signaling as a specific mechanism linking gut inflammation to blood vessel dysfunction. NK1 receptor blockers could be a new therapeutic angle.","specificNumbers":"EFS-mediated sensory vasodilation severely impaired; NK1 blockade restored vasodilation; both CGRP and SP release decreased","methodology":"Researchers used IL-10 knockout mice (a standard IBD model) and measured blood vessel responses in mesenteric arteries. They used electrical field stimulation to activate nerves, measured CGRP and substance P release, assessed nerve density and receptor expression, and tested the effects of blocking NK1 receptors. Tested in both male and female mice.","limitations":"This was tested in mice, not people. The IL-10 knockout model mimics some but not all features of human IBD. Blood vessel responses measured in isolated arteries may differ from responses in the intact body. The study did not test NK1 blockers as a treatment in living mice with IBD symptoms."},{"rthcId":"RPEP-05652","title":"Expression profiling of ileal mucosa in asthma reveals upregulation of innate immunity and genes characteristic of Paneth and goblet cells.","authors":"Nowak, Jan K; Dworacka, Marzena; Gubaj, Nazgul; Dossimov, Arystan; Dossimov, Zhumabek; Walkowiak, Jarosław","year":2021,"journal":"Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology, 17(1), 82","doi":"10.1186/s13223-021-00584-9","pmid":"34332619","tags":["antimicrobial-peptides","immune-function","respiratory"],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"The ileum was the only tissue with significant gene expression differences between asthma patients and controls. Over 1,150 genes were overexpressed and 380 were underexpressed.\n\nThe most overexpressed genes included FCGBP (a mucus-associated protein, 8-fold higher), MUC2 (mucin 2, about 7-fold higher), and DEFA1B (alpha-defensin 1B, about 6.5-fold higher). Gene pathway analysis pointed to the immune system, interleukins 4 and 13, and antimicrobial peptides.\n\nThe overexpressed genes were characteristic of Paneth cells (which produce defensins) and goblet cells (which produce mucus). Some gene changes overlapped with patterns seen in Crohn's disease ileum, including shared overexpression of STAT1 and XBP1. This overlap was statistically significant (p = 3.66 x 10^-7).\n\nNo significant changes were found in the colon, rectum, platelets, or any white blood cell subset.","whyItMatters":"The gut-lung axis is an emerging concept in immunology. This study provides direct evidence that asthma involves immune changes in the small intestine, not just the lungs. The defensin and mucus gene overexpression suggests the gut's innate immune system is ramped up in asthma patients.","specificNumbers":"DEFA1B logFC=2.73 (pFDR=0.024); MUC2 logFC=2.78; 1,150 genes overexpressed; overlap with Crohn's p=3.66e-7","methodology":"Researchers collected biopsies from the ileum, transverse colon, and rectum of 15 asthma patients and 15 matched controls from the CEDAR cohort. They also analyzed gene expression from platelets and five types of white blood cells. Groups were matched for age, BMI, sex (80% female), and smoking rates (13.3% each).","limitations":"With only 15 patients per group, this is a small study. The population was 80% female, limiting generalizability to males. The study found correlations, not causes. The CEDAR cohort may not represent all asthma subtypes. The study did not test whether gut changes preceded or followed asthma onset."},{"rthcId":"RPEP-05653","title":"Post-weight loss changes in fasting appetite- and energy balance-related hormone concentrations and the effect of the macronutrient content of a weight maintenance diet: a randomised controlled trial.","authors":"Näätänen, Mari; Kolehmainen, Marjukka; Laaksonen, David E; Herzig, Karl-Heinz; Poutanen, Kaisa; Karhunen, Leila","year":2021,"journal":"European journal of nutrition, 60(5), 2603-2616","doi":"10.1007/s00394-020-02438-3","pmid":"33263788","tags":["ghrelin","obesity-metabolism"],"studyType":"clinical trial","evidenceStrength":"strong","keyFinding":"After 7 weeks of very-low-energy dieting producing 12 kg weight loss (P < 0.001), participants were randomized to higher-satiety food (HSF, more protein/fiber, less fat) or lower-satiety food (LSF) diets for 24-week weight maintenance. Key findings:\n\n- Diet composition made no difference: HSF and LSF groups showed identical changes in fasting ghrelin, leptin, insulin, and glucose\n- Weight regain was modest: only 1.3 kg (P = 0.004) over 24 weeks\n- Hormonal adaptations persisted: ghrelin increased, leptin/insulin/glucose decreased vs. pre-diet (all P < 0.001)\n- Peptide YY (PYY) did not differ from pre-diet levels\n- Body composition tracking: ghrelin inversely correlated with fat-free mass changes (P = 0.002); leptin and insulin positively correlated with fat mass changes (P < 0.05)","whyItMatters":"Weight regain after dieting is one of the biggest challenges in obesity treatment. The hormonal adaptations that drive regain — increased ghrelin and decreased leptin — are powerful and persistent. This study shows that even a well-designed high-protein, high-fiber diet cannot override these hormonal changes. This has important implications for understanding why dietary approaches alone often fail for long-term weight maintenance and supports the rationale for pharmacological interventions (like GLP-1RA drugs) that can counteract these hormonal adaptations.","specificNumbers":"N=82; -12 kg (p<0.001); +1.3 kg regain; ghrelin up; leptin, insulin, glucose down (p<0.001); PYY unchanged; HSF vs LSF: no hormone differences","methodology":"Registered randomized controlled trial (ISRCTN 67529475). 82 men and women with obesity completed a 7-week very-low-energy diet (VLED), then were randomized to consume isoenergetic higher-satiety or lower-satiety foods with different macronutrient compositions for 24 weeks of weight maintenance. Fasting appetite-related hormones (ghrelin, leptin, insulin, PYY) and glucose were measured at multiple timepoints. Body composition (fat mass and fat-free mass) was assessed. Associations between hormone changes and body composition changes were analyzed.","limitations":"Moderate sample size (82 participants) limits subgroup analyses. Only fasting hormone levels were measured — postprandial peptide responses (which may differ more between diets) were not assessed. The 24-week maintenance period may be too short to capture longer-term hormonal adaptation. Dietary compliance was self-reported. PYY was measured only in the fasting state, where it may be less informative than postprandial PYY responses."},{"rthcId":"RPEP-05654","title":"Antimicrobial Activity of Snake β-Defensins and Derived Peptides.","authors":"Oguiura, Nancy; Corrêa, Poliana Garcia; Rosmino, Isabella Lemos; de Souza, Ana Olívia; Pasqualoto, Kerly Fernanda Mesquita","year":2021,"journal":"Toxins, 14(1)","doi":"10.3390/toxins14010001","pmid":"35050978","tags":["antimicrobial-peptides","venom-peptides","peptide-design"],"studyType":"basic-research","evidenceStrength":"preliminary","keyFinding":"Linear beta-defensins from snakes were most active against E. coli, M. luteus, C. freundii, and S. aureus. Shorter derived peptides (7-14 amino acids) also showed antibacterial activity against those bacteria plus K. pneumoniae.\n\nHowever, none of the derived peptides killed any of the four fungi tested (C. albicans, C. neoformans, T. rubrum, A. fumigatus). The key difference was the cysteine-to-serine substitution used to create the linear peptides. This suggests that the disulfide bridges formed by cysteines are essential for antifungal activity but less important for killing bacteria.\n\nAdding tryptophan (an amino acid) to the derived peptides improved their antibacterial potency. The researchers concluded that while snake beta-defensins are not the most powerful antimicrobials, they serve as useful starting templates for designing new antibiotics.","whyItMatters":"Antibiotic resistance is a growing global problem. Venom-derived peptides are an underexplored source of new antibiotics. This study maps which structural features matter for antibacterial versus antifungal activity, guiding future peptide drug design.","specificNumbers":"Active against E. coli, M. luteus, C. freundii, S. aureus, K. pneumoniae; inactive against 4 fungal species; 7-14 mer derived peptides","methodology":"Researchers deduced peptide sequences from previously described beta-defensin genes in Brazilian snakes. They synthesized full-length peptides (~40 amino acids) and shorter derived peptides (7-14 amino acids) using bioisosterism (replacing cysteines with serines). They tested antimicrobial activity using microbroth dilution assays against multiple bacterial and fungal species.","limitations":"All testing was done in lab conditions (in vitro). The peptides were not tested in animals or humans. The study only tested a limited panel of bacteria and fungi. The derived peptides had reduced overall potency compared to the full-length versions. No toxicity to human cells was assessed."},{"rthcId":"RPEP-05655","title":"Feasibility of a self-assembling peptide hydrogel scaffold for meniscal defect: An in vivo study in a rabbit model.","authors":"Okuno, Nobuhiro; Otsuki, Shuhei; Aoyama, Jo; Nakagawa, Kosuke; Murakami, Tomohiko; Ikeda, Kuniaki; Hirose, Yoshinobu; Wakama, Hitoshi; Okayoshi, Tomohiro; Okamoto, Yoshinori; Hirano, Yoshiaki; Neo, Masashi","year":2021,"journal":"Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 39(1), 165-176","doi":"10.1002/jor.24841","pmid":"32852842","tags":["peptide-delivery","bone-joint","wound-healing"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Full-thickness cylindrical defects (2.0 mm diameter) were punched into the inner avascular zone of rabbit medial menisci. This area does not heal well because it lacks blood supply. The KI24RGDS peptide hydrogel was placed into the left knee defects, while right knee defects were left empty as controls.\n\nThe hydrogel group scored significantly higher on macroscopic meniscus assessments at 2, 4, and 8 weeks after surgery. Histological scores (microscopic tissue quality) were significantly better at 2, 4, 8, and 12 weeks.\n\nAt 12 weeks, immunostaining confirmed the repair tissue contained both type I and type II collagen, which is the composition of natural meniscus. The KI24RGDS hydrogel contains RGDS sequences (cell-binding signals) that help cells attach and multiply. It also mimics the structure of natural extracellular matrix.","whyItMatters":"Meniscus tears in the avascular zone are a common and difficult orthopedic problem. These injuries often lead to osteoarthritis because the tissue cannot heal on its own. A biodegradable peptide scaffold that promotes tissue regeneration could fill an unmet clinical need.","specificNumbers":"2.0 mm defects; macroscopic scores significant at 2, 4, 8 weeks; histological scores significant at 2, 4, 8, 12 weeks; type I and II collagen at 12 weeks","methodology":"Researchers created 2.0 mm full-thickness defects in the avascular zone of the medial meniscus in 40 rabbit knees. Left knees received the KI24RGDS peptide hydrogel; right knees were left empty. Animals were assessed at 2, 4, 8, and 12 weeks using macroscopic scoring, histological grading, and immunohistochemistry for collagen types I and II.","limitations":"This was tested in rabbits, not people. Rabbit meniscus biology differs from human meniscus. The follow-up was only 12 weeks, and longer-term outcomes (including whether repair tissue holds up under stress) were not assessed. The study did not test mechanical function of the repaired meniscus. The 2.0 mm defect is small compared to typical human meniscus tears."},{"rthcId":"RPEP-05656","title":"Thymosin β4 and β10 are highly expressed at the deep infiltrative margins of colorectal cancer - A mass spectrometry analysis.","authors":"Olianas, A; Serrao, S; Piras, V; Manconi, B; Contini, C; Iavarone, F; Pichiri, G; Coni, P; Zorcolo, L; Orrù, G; Messana, I; Faa, G; Castagnola, M; Fanni, D; Cabras, T","year":2021,"journal":"European review for medical and pharmacological sciences, 25(23), 7285-7296","doi":"10.26355/eurrev_202112_27422","pmid":"34919228","tags":["thymosin-beta-4","cancer"],"studyType":"observational","evidenceStrength":"preliminary","keyFinding":"Using mass spectrometry, researchers measured thymosin beta-4 (Tb4) and thymosin beta-10 (Tb10) in three zones: deep tumor tissue, superficial tumor tissue, and normal mucosa from 18 colorectal cancer patients.\n\nBoth peptides were significantly higher in the deep invasive margins of tumors compared to the surface. This is the part of the tumor actively pushing into surrounding tissue.\n\nTb4 and Tb10 levels were also linked to cancer staging. They were highest in patients with Dukes stage B (tumor growing through the bowel wall) and in those with a budding index of 2 (meaning more tumor cells were breaking away from the main mass). Tumor budding is a key indicator of aggressive cancer behavior.\n\nThe researchers also identified different modified forms (proteoforms) of these thymosins using high-resolution mass spectrometry.","whyItMatters":"Colorectal cancer kills because it invades and spreads. Finding that thymosin beta-4 and beta-10 are concentrated at the invasive front suggests they actively promote cancer invasion. They could serve as biomarkers for aggressive tumors or as targets for new treatments.","specificNumbers":"Tb4 and Tb10 upregulated in deep tumor; highest in Dukes stage B and budding index 2; HPLC-ESI-IT-MS analysis","methodology":"Researchers collected deep tumor, superficial tumor, and normal mucosa samples from 18 colorectal cancer patients. Thymosin beta-4 and beta-10 concentrations were measured by HPLC coupled to electrospray-ion trap mass spectrometry. Results were analyzed using t-test and ANOVA. Modified forms were identified by high-resolution tandem mass spectrometry.","limitations":"Only 18 patients were included, which is a small sample. The study measured peptide levels but did not prove that thymosin beta-4 or beta-10 cause invasion (correlation, not causation). Functional experiments (like blocking these peptides to see if invasion stops) were not performed. The study did not include survival or treatment outcome data."},{"rthcId":"RPEP-05657","title":"Synthetic Peptide Derived from Scorpion Venom Displays Minimal Toxicity and Anti-infective Activity in an Animal Model.","authors":"Oliveira, Cyntia Silva; Torres, Marcelo Der Torossian; Pedron, Cibele Nicolaski; Andrade, Viviane Brito; Silva, Pedro Ismael; Silva, Fernanda Dias; de la Fuente-Nunez, Cesar; Oliveira, Vani Xavier","year":2021,"journal":"ACS infectious diseases, 7(9), 2736-2745","doi":"10.1021/acsinfecdis.1c00261","pmid":"34463484","tags":["venom-peptides","antimicrobial-peptides","peptide-design","infection"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"The original peptide IsCT1-NH2 from the scorpion Opisthacanthus madagascariensis is a potent antimicrobial but too toxic to human cells. The team made versions with multiple amino acid substitutions that changed the net charge from +3 to +6.\n\nIncreasing the net charge to +4 produced the best balance. The lead peptide [A]1[K]3[F]5[K]8-IsCT1-NH2 (net charge +4) significantly reduced toxicity to human red blood cells while increasing antibacterial activity against both Gram-negative and Gram-positive bacteria.\n\nIn a mouse infection model, the lead peptide showed enhanced anti-infective activity compared to the original. The mechanism involved improved ability to punch holes in the outer bacterial membrane and disrupt the inner membrane's electrical charge.\n\nThis demonstrates that simple charge-tuning of venom peptides can convert them from lab curiosities into potential therapeutics.","whyItMatters":"Antibiotic resistance is a critical global health problem. Venoms contain thousands of antimicrobial peptides, but most are too toxic for clinical use. This study provides a straightforward method (charge tuning) to reduce toxicity while preserving or improving antibacterial power, potentially unlocking many other venom peptides for development.","specificNumbers":"Net charge +3 to +6 tested; +4 lead compound; active against Gram-positive and Gram-negative bacteria; reduced hemolysis","methodology":"Researchers created multiple variants of the IsCT1 peptide with different amino acid substitutions to vary net charge from +3 to +6. They tested each variant for antimicrobial activity (microbroth dilution against Gram-positive and Gram-negative bacteria), toxicity to human red blood cells, and mechanism of action (outer membrane permeability and cytoplasmic membrane depolarization). The lead peptide was tested in a mouse infection model.","limitations":"The mouse infection model is an early-stage test. The study did not assess long-term safety, organ toxicity, or whether the peptide works against multidrug-resistant clinical isolates. The peptide's stability in blood (pharmacokinetics) was not reported. Manufacturing costs for therapeutic peptides remain a challenge."},{"rthcId":"RPEP-05658","title":"Analysis of a gene family for PDF-like peptides from Arabidopsis.","authors":"Omidvar, Reza; Vosseler, Nadine; Abbas, Amjad; Gutmann, Birgit; Grünwald-Gruber, Clemens; Altmann, Friedrich; Siddique, Shahid; Bohlmann, Holger","year":2021,"journal":"Scientific reports, 11(1), 18948","doi":"10.1038/s41598-021-98175-6","pmid":"34556705","tags":["antimicrobial-peptides","peptide-design"],"studyType":"basic-research","evidenceStrength":"preliminary","keyFinding":"Arabidopsis contains nine PdfL genes that are related to but distinct from standard plant defensins. All nine are expressed at low levels across most plant tissues.\n\nTwo PdfL peptides were produced in bacteria and tested for antimicrobial activity. Both were highly active against fungi but had lower activity against bacteria. At higher concentrations, they caused hyperbranching and swollen tips in the fungal pathogen Fusarium graminearum, which are hallmarks of antifungal peptide action.\n\nPlants overexpressing most PdfL genes (using the 35S promoter) gained enhanced resistance to F. oxysporum, a devastating plant pathogen that causes wilt disease. The one exception was PdfL4.1. When any PdfL peptide was expressed at high levels in tobacco leaves, PDFL1.4 caused complete tissue death after 7 days, while others caused only small lesions.","whyItMatters":"Plant defensins are promising natural antifungal agents. Discovering a new family of nine defensin-like genes expands the toolkit available for crop protection. The antifungal activity and in planta resistance data make these candidates for developing fungal-resistant crops.","specificNumbers":"9 PdfL genes; 2 peptides tested antifungal; 8 of 9 enhanced F. oxysporum resistance; PDFL1.4 caused tissue death","methodology":"Researchers identified nine PdfL genes by genomic analysis. They used GUS reporter fusions to map expression patterns across tissues. Two peptides were produced recombinantly in E. coli and tested in antimicrobial assays. Overexpression lines were created using the 35S CaMV promoter. Resistance to F. oxysporum was tested in planta. Transient expression in tobacco leaves was used to assess tissue effects.","limitations":"This is a plant study with no direct human health application. Only two of nine PdfL peptides were produced and tested in vitro. The antifungal assays used lab conditions that may not reflect field performance. The overexpression used a strong promoter (35S), which may cause levels higher than practical for crop use. The PDFL1.4 toxicity to plant tissue raises safety concerns for some family members."},{"rthcId":"RPEP-05659","title":"Indirect Comparison of Topiramate and Monoclonal Antibodies Against CGRP or Its Receptor for the Prophylaxis of Episodic Migraine: A Systematic Review with Meta-Analysis.","authors":"Overeem, Lucas Hendrik; Raffaelli, Bianca; Mecklenburg, Jasper; Kelderman, Tim; Neeb, Lars; Reuter, Uwe","year":2021,"journal":"CNS drugs, 35(8), 805-820","doi":"10.1007/s40263-021-00834-9","pmid":"34272688","tags":["neuropeptides","pain","clinical-trials"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"The CGRP pathway antibodies reduced monthly migraine days by 1.55 days more than placebo (8 studies, 5,545 patients). Topiramate reduced them by 1.11 days more than placebo (4 studies, 1,575 patients). The difference between the two was not statistically significant (p = 0.15), meaning they work about equally well.\n\nThe safety story was dramatically different. Cognitive side effects (brain fog, word-finding trouble) and sensory/pain side effects occurred significantly more often with topiramate. The number needed to treat (NNT) was similar: 6 for CGRP antibodies and 7 for topiramate. But the number needed to harm (NNH) was 130 for CGRP antibodies versus just 9 for topiramate.\n\nThis translates to a likelihood to help over harm (LHH) of 24.3 to 1 for CGRP antibodies versus 1.8 to 1 for topiramate. In plain terms, for every person harmed by CGRP antibodies, about 24 are helped. For topiramate, fewer than 2 are helped for every 1 harmed.","whyItMatters":"Head-to-head trials between CGRP antibodies and topiramate do not exist. This indirect comparison fills that gap with data from 13 randomized trials. The finding that both work similarly but CGRP antibodies are far safer helps clinicians and patients make informed treatment choices.","specificNumbers":"CGRP mAbs -1.55 MMDs vs placebo; topiramate -1.11 MMDs; NNT 6 vs 7; NNH 130 vs 9; LHH 24.3:1 vs 1.8:1","methodology":"Researchers searched PubMed, Cochrane CENTRAL, and ClinicalTrials.gov from 2000 to 2020 for controlled trials of CGRP antibodies and topiramate in episodic migraine. They included 13 trials (7,557 patients total): 3 erenumab, 2 galcanezumab, 2 fremanezumab, 1 eptinezumab, and 5 topiramate. They used random-effects meta-analysis with indirect comparison methods. Risk of bias was assessed with the RoB2 tool.","limitations":"This is an indirect comparison, not a head-to-head trial. The two drug classes were studied in different patient populations and trial designs, which introduces uncertainty. The topiramate trials are older, and patient selection criteria may have differed. Some endpoints had significant between-study heterogeneity. The analysis did not include cost, which is a major factor in real-world prescribing."},{"rthcId":"RPEP-05660","title":"Clinical Pharmacokinetics of Oral Semaglutide: Analyses of Data from Clinical Pharmacology Trials.","authors":"Overgaard, Rune V; Navarria, Andrea; Ingwersen, Steen H; Bækdal, Tine A; Kildemoes, Rasmus Juul","year":2021,"journal":"Clinical pharmacokinetics, 60(10), 1335-1348","doi":"10.1007/s40262-021-01025-x","pmid":"33969456","tags":["semaglutide","bioavailability","oral-peptides"],"studyType":"pharmacokinetic","evidenceStrength":"strong","keyFinding":"Using data from six clinical trials, researchers extended a pharmacokinetic model to describe oral semaglutide absorption, distribution, and elimination. The key finding is that oral bioavailability is remarkably low at just 0.8% under recommended dosing conditions (30 minutes fasting, taken with 120 mL or less of water).\n\nFasting longer after taking the pill increased how much drug got absorbed. Drinking more water decreased absorption. Body weight also affected exposure levels.\n\nThe day-to-day variation in how much drug gets absorbed from each individual pill was very high at 137%. However, because semaglutide has a long half-life and is taken daily, this variation smooths out to just 33% at steady state (when levels stabilize after days of dosing).\n\nThere was no significant difference in oral bioavailability between healthy people and those with type 2 diabetes.","whyItMatters":"Understanding why oral semaglutide has such low bioavailability and high variability helps explain its strict dosing requirements. It also reassures that despite wild day-to-day swings in absorption, the drug still reaches consistent therapeutic levels with daily dosing.","specificNumbers":"0.8% oral bioavailability; 137% within-subject daily variability; 33% at steady state; 5-10 mg doses; 30-min fasting recommended","methodology":"Researchers used a previously developed two-compartment pharmacokinetic model from subcutaneous and intravenous semaglutide data. They extended it with data from six oral semaglutide trials in healthy volunteers and people with kidney or liver impairment. Doses ranged from 5-10 mg. A separate analysis used data from a type 2 diabetes trial. The model was estimated using population pharmacokinetic methods.","limitations":"The model is based on clinical trial data where patients followed strict dosing instructions. Real-world adherence to the 30-minute fasting requirement and water restrictions may be lower, potentially reducing effectiveness. The study did not model food effects (eating too soon). Only doses up to 10 mg were studied; the 14 mg clinical dose was not included in all analyses."},{"rthcId":"RPEP-05661","title":"GLP-1RA and SGLT2i: Cardiovascular Impact on Diabetic Patients.","authors":"Pablo, Aschner; Evelyn, Blanc; Claudia, Folino; Yanina, Morosán A","year":2021,"journal":"Current hypertension reviews, 17(2), 149-158","doi":"10.2174/1573402116999201124123549","pmid":"33238857","tags":["glp-1","semaglutide","liraglutide","cardiovascular","diabetes"],"studyType":"review","evidenceStrength":"strong","keyFinding":"For SGLT2 inhibitors, empagliflozin, canagliflozin, and dapagliflozin all showed a hazard ratio of 0.86 for major cardiovascular events (MACE), meaning a 14% relative risk reduction. The number needed to treat (NNT) to prevent one MACE event in 5 years was 38, 44, and 33 respectively. For heart failure hospitalization, the reductions were even larger: HR 0.65, 0.67, and 0.73 with NNTs of 44, 62, and 98.\n\nFor GLP-1 receptor agonists, the results varied more. Semaglutide had the strongest effect (HR 0.74, a 26% reduction). Liraglutide showed HR 0.87, albiglutide HR 0.78, and dulaglutide HR 0.88. Lixisenatide (HR 1.02) and exenatide (HR 0.91) showed no significant benefit. None of the GLP-1 drugs reduced heart failure hospitalization.\n\nThe key practical finding: for both drug classes, treating fewer than 50 patients for 5 years prevents one major heart event. This level of benefit has changed how diabetes is treated.","whyItMatters":"These findings have fundamentally changed diabetes treatment guidelines. Both SGLT2 inhibitors and GLP-1 drugs now have preferred status for patients with type 2 diabetes and heart disease. The NNT calculations make the benefit concrete and practical for clinical decision-making.","specificNumbers":"SGLT2i MACE HR 0.86 (NNT 33-44); semaglutide MACE HR 0.74; liraglutide HR 0.87; SGLT2i HHF HR 0.65-0.73; NNT <50 for both classes","methodology":"This is a narrative review of cardiovascular outcome trials published over the past 10 years. The authors compiled hazard ratios for MACE and heart failure hospitalization from landmark trials and calculated NNT values for 5-year prevention of one cardiovascular event.","limitations":"This is a narrative review, not a systematic review or meta-analysis. The NNT calculations are approximations based on trial-level data. Different trials had different patient populations, follow-up periods, and definitions of MACE. Direct comparisons between SGLT2 inhibitors and GLP-1 drugs were not available. Cost and real-world adherence were not addressed."},{"rthcId":"RPEP-05662","title":"Computational avenues in oral protein and peptide therapeutics.","authors":"Pandya, Anjali K; Patravale, Vandana B","year":2021,"journal":"Drug discovery today, 26(6), 1510-1520","doi":"10.1016/j.drudis.2021.03.003","pmid":"33684525","tags":["oral-peptides","bioavailability","peptide-design","peptide-delivery"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Oral delivery of peptide drugs faces three main barriers: enzymatic degradation (stomach acid and enzymes break them apart), poor membrane permeability (they are too large and charged to cross the gut lining), and instability (they unfold and lose function).\n\nComputer-aided drug design (CADD) addresses these by modeling molecular interactions at the atomic level. Researchers can simulate how a peptide interacts with its receptor, screen formulation ingredients for compatibility, and predict which chemical modifications might improve stability or absorption.\n\nThe review highlights that CADD can pre-screen excipients (inactive ingredients in the formulation) and predict absorption before expensive lab experiments. This speeds up development and reduces costs for oral peptide formulations.","whyItMatters":"Most peptide drugs must be injected because oral delivery is extremely difficult. Any advance that makes oral peptide delivery practical would improve patient compliance and expand who can use these drugs. Computational tools can accelerate this process by reducing the need for trial-and-error experiments.","specificNumbers":"3 barriers: enzymatic degradation, poor permeability, instability; CADD techniques: molecular docking, molecular dynamics, QSAR","methodology":"This is a narrative review covering the application of computational approaches (molecular docking, molecular dynamics simulation, QSAR modeling, and other CADD techniques) to the challenge of oral protein and peptide delivery. It surveys published examples and general principles.","limitations":"This is a broad review without new experimental data. Computational predictions do not always match real-world results. Many of the approaches described are still theoretical or early-stage. The review does not quantify how much CADD actually improves success rates or reduces costs versus traditional methods."},{"rthcId":"RPEP-05663","title":"A study of the sequential treatment of acute heart failure with sacubitril/valsartan by recombinant human brain natriuretic peptide: A randomized controlled trial.","authors":"Pang, Zhihua; Pan, Chang; Yao, Zhuhua; Ren, Ying; Tian, Liuyang; Cui, Jian; Liu, Ximei; Zhang, Lijun; Chen, Ying","year":2021,"journal":"Medicine, 100(16), e25621","doi":"10.1097/MD.0000000000025621","pmid":"33879733","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05664","title":"Cathelicidin levels in nasal secretions are associated with the severity of acute bronchiolitis.","authors":"Papadaki, Maria; Marmarinos, Antonios; Tsolia, Maria; Gourgiotis, Dimitrios; Soldatou, Alexandra","year":2021,"journal":"Pediatric pulmonology, 56(6), 1673-1680","doi":"10.1002/ppul.25349","pmid":"33656266","tags":["ll-37","antimicrobial-peptides","immune-function","respiratory"],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"LL-37 levels in nasal secretions were inversely associated with multiple measures of bronchiolitis severity. Higher LL-37 meant:\n\n- Shorter hospitalization (rho = -0.340, p = 0.001)\n- Less medication use (p = 0.001)\n- Shorter oxygen supplementation (rho = -0.339, p = 0.001)\n- Shorter IV fluid administration (rho = -0.323, p = 0.001)\n\nThese associations remained significant after adjusting for confounding factors like age and other variables.\n\nNotably, serum vitamin D levels were not associated with nasal LL-37 levels, challenging the assumption that vitamin D drives LL-37 production in the airways. Beta-defensin-2 nasal levels also showed no connection to disease severity.","whyItMatters":"Bronchiolitis is the leading cause of hospitalization in infants. There is no specific treatment. If LL-37 plays a protective role, it could become a target for prevention or treatment strategies. The lack of connection between vitamin D and nasal LL-37 challenges a common assumption in the field.","specificNumbers":"N=153; median age 3.1 months; LL-37 vs hospitalization rho=-0.340; vs O2 rho=-0.339; all p=0.001","methodology":"This was a prospective cohort study at a single pediatric center from November 2014 to April 2017. Researchers enrolled 153 infants (aged 0-18 months) with their first episode of acute bronchiolitis. They measured serum 25(OH)D (vitamin D), nasal LL-37, and nasal beta-defensin-2 levels. Disease severity was measured by length of hospitalization, oxygen duration, medication use, and IV fluid duration. Statistical analysis used non-parametric tests and multiple regression.","limitations":"This is an observational study and cannot prove LL-37 caused less severe disease. Higher LL-37 might simply reflect a stronger immune system. The study was at a single center, limiting generalizability. Viral types causing bronchiolitis were not reported, and different viruses may trigger different LL-37 responses. The correlation coefficients (rho around -0.34) are moderate."},{"rthcId":"RPEP-05665","title":"The role of the multifunctional antimicrobial peptide melittin in gene delivery.","authors":"Paray, Bilal Ahamad; Ahmad, Aqeel; Khan, Javed Masood; Taufiq, Faisal; Pathan, Aslam; Malik, Ajamaluddin; Ahmed, Mohammad Z","year":2021,"journal":"Drug discovery today, 26(4), 1053-1059","doi":"10.1016/j.drudis.2021.01.004","pmid":"33450177","tags":["venom-peptides","peptide-delivery","cell-penetrating"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"One of the biggest barriers in gene therapy is the endosomal trap. Cells engulf nanoparticles carrying therapeutic genes, but the particles get stuck inside endosomes and are destroyed before they can deliver their cargo to the cell nucleus.\n\nMelittin, a 26-amino-acid peptide from bee venom, can disrupt endosomal membranes and release the trapped cargo. However, melittin is extremely toxic to mammalian cells at normal concentrations because it also destroys the outer cell membrane.\n\nResearchers have addressed this by modifying melittin's amino acid sequence to reduce its toxicity while preserving its membrane-disrupting ability. Strategies include making pH-sensitive versions that only activate inside acidic endosomes (where the gene cargo is trapped) and conjugating melittin to nanoparticle carriers so it acts locally rather than freely.","whyItMatters":"Gene therapy holds enormous potential but is limited by poor delivery into cells. Endosomal escape is a critical bottleneck. Melittin-based approaches offer a powerful solution if the toxicity problem can be solved. This review maps the state of that effort.","specificNumbers":"Melittin: 26 amino acids; key strategies: sequence modification, pH-sensitive designs, nanoparticle conjugation","methodology":"This is a narrative review covering published research on melittin analogs for gene delivery. It describes endosomal escape mechanisms, melittin structure-activity relationships, and engineering strategies to reduce toxicity.","limitations":"This is a review without new experimental data. Many of the engineered melittin variants are still in early preclinical stages. Long-term safety of modified melittin in living organisms is largely unknown. The review focuses on gene delivery but melittin's effects on other cellular processes are not fully addressed."},{"rthcId":"RPEP-05666","title":"Ectopic Expression of Human Thymosin β4 Confers Resistance to Legionella pneumophila during Pulmonary and Systemic Infection in Mice.","authors":"Park, Bonggoo; Shin, Min Hwa; Kim, Jiyoung; Park, Gayoung; Ryu, Yun-Kyoung; Lee, Jae-Wook; Kim, Tae Jin; Moon, Eun-Yi; Lee, Kyung-Mi","year":2021,"journal":"Infection and immunity, 89(4)","doi":"10.1128/IAI.00735-20","pmid":"33468581","tags":["thymosin-beta-4","infection","immune-function","inflammation"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Tb4-overexpressing transgenic mice showed significantly lower bacterial loads in the lungs after Legionella infection. Their lungs had less damage: fewer hyaline membranes (a sign of severe lung injury), fewer necrotic abscesses, and less infiltration of immune cells (neutrophils, CD4+ and CD8+ T cells).\n\nThe fluid washed from the lungs (bronchoalveolar lavage) of Tb4 mice had stronger bactericidal activity against added Legionella, showing Tb4 helped directly kill bacteria.\n\nTb4 mice also produced less of the inflammatory signals IL-1b and TNF-alpha, both in the lungs and in bone marrow-derived macrophages tested in the lab. This anti-inflammatory effect appeared to work through reduced Toll-like receptor (TLR) activation, as it was affected by stimulating TLR2, TLR4, TLR5, or TLR9.\n\nIn a systemic sepsis model, Tb4 transgenic mice survived Legionella challenge significantly better than wild-type controls.","whyItMatters":"Legionnaires' disease kills 5-10% of those who contract it, and antibiotic resistance is a growing concern. This study shows thymosin beta-4 provides dual protection: it helps kill the bacteria directly AND reduces the inflammatory damage that makes the disease deadly. This dual mechanism is unusual and potentially very valuable.","specificNumbers":"Lower bacterial loads; reduced IL-1b, TNF-alpha; improved sepsis survival; TLR2/4/5/9 involvement","methodology":"Researchers used transgenic mice that constitutively overexpress human thymosin beta-4. They infected mice with Legionella pneumophila via the lungs (pulmonary model) and systemically (sepsis model). They measured bacterial counts, lung histology, immune cell infiltration, cytokine levels, bactericidal activity of lung wash fluid, and survival. Bone marrow-derived macrophages were also tested in vitro with various TLR ligands.","limitations":"This was tested in mice, not people. Transgenic mice constitutively overexpress Tb4, which does not mimic how a drug would be given. The study did not test whether administering Tb4 as a treatment (rather than having it already present) would produce the same benefit. The Legionella model may not fully represent human Legionnaires' disease."},{"rthcId":"RPEP-05667","title":"Inflammasome-mediated Inflammation by Malassezia in human keratinocytes: A comparative analysis with different strains.","authors":"Park, Hye Ree; Oh, Jee Hye; Lee, Yu Jin; Park, Song Hee; Lee, Yang Won; Lee, Seongju; Kang, Hoon; Kim, Jung Eun","year":2021,"journal":"Mycoses, 64(3), 292-299","doi":"10.1111/myc.13214","pmid":"33206994","tags":["antimicrobial-peptides","ll-37","skin-repair","immune-function"],"studyType":"basic-research","evidenceStrength":"preliminary","keyFinding":"M. restricta and M. globosa activated the NLRP3-ASC inflammasome in human keratinocytes, triggering IL-1β secretion — a key inflammatory signal. All three Malassezia species variably induced the antimicrobial peptides thymic stromal lymphopoietin, β-defensin 2, and LL-37.\n\nEach species created a distinct inflammatory profile: M. sympodialis significantly increased IL-8 and IL-22 protein levels, while M. globosa increased CCL17 mRNA and M. restricta increased CCL22 mRNA. This species-specific pattern of inflammasome activation, cytokine release, and antimicrobial peptide induction suggests that different Malassezia species may drive the distinct clinical presentations of conditions like dandruff versus atopic dermatitis.","whyItMatters":"Malassezia is the most common fungus on human skin, yet its exact role in causing skin disease has been hard to pin down. By showing that different species trigger fundamentally different immune responses — including distinct antimicrobial peptide patterns — this study provides a molecular explanation for why Malassezia-associated conditions vary so much clinically. This could eventually guide species-specific treatment strategies.","specificNumbers":"NLRP3-ASC activated by M. restricta and M. globosa; LL-37 and beta-defensin 2 variably induced; IL-8/IL-22 increased by M. sympodialis","methodology":"Researchers exposed HaCaT human keratinocyte cells to three Malassezia species — M. restricta, M. globosa, and M. sympodialis — and then measured multiple immune outputs. They assessed NLRP3 inflammasome activation, IL-1β secretion, expression of pro-inflammatory cytokines (IL-8, IL-22) and chemokines (CCL17, CCL22) at the mRNA and protein level, and production of antimicrobial peptides including LL-37 and beta-defensin 2.","limitations":"This was an in vitro study using a single keratinocyte cell line (HaCaT), which does not capture the full complexity of intact skin with its multiple cell types, immune cells, and microbiome. Only three of the 14+ known Malassezia species were tested. The fungal concentrations used in the lab may not reflect natural skin colonization levels. No patient tissue or clinical correlation was included."},{"rthcId":"RPEP-05668","title":"Elevated serum substance P level as a predictive marker for moderately emetogenic chemotherapy-induced nausea and vomiting: A prospective cohort study.","authors":"Park, Hyung Soon; Won, Hye Sung; An, Ho Jung; Cho, Sung Shim; Kim, Hyun Ho; Sun, Der Sheng; Ko, Yoon Ho; Shim, Byoung Yong","year":2021,"journal":"Cancer medicine, 10(3), 1057-1065","doi":"10.1002/cam4.3693","pmid":"33369184","tags":["neuropeptides","cancer","side-effects"],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"Of 82 patients (mostly colorectal and gastric cancer), 55% experienced nausea and 18% experienced vomiting during their first chemotherapy cycle.\n\nPatients with higher baseline substance P levels were 2.6 times more likely to have chemotherapy-induced nausea (OR 2.6, 95% CI 1.02-6.62, p = 0.046). For vomiting, the trend was similar but did not reach statistical significance (OR 1.72, p = 0.395).\n\nSubstance P is the target of NK1 receptor antagonists (NK1-RAs), drugs specifically designed to block nausea. These drugs are typically reserved for high-risk chemotherapy regimens. The finding suggests that patients receiving moderate-risk chemo who have high substance P levels might benefit from getting NK1-RAs too.\n\nLeptin and ghrelin, two other peptides measured, were not significant predictors of nausea or vomiting.","whyItMatters":"Chemotherapy-induced nausea remains a major quality-of-life issue. A simple blood test for substance P before treatment could identify high-risk patients who need stronger anti-nausea protection, personalizing supportive care.","specificNumbers":"N=82; 55% nausea; 18% vomiting; substance P OR 2.6 (CI 1.02-6.62, p=0.046) for nausea","methodology":"This was a prospective cohort study of 82 patients receiving moderately emetogenic chemotherapy. Researchers measured blood levels of leptin, ghrelin, and substance P at baseline, day 3, and day 14 of the first chemotherapy cycle. Nausea and vomiting were tracked daily for the first 4 days.","limitations":"With 82 patients, this is a small study. The vomiting result did not reach statistical significance, possibly due to the small number who vomited (15 patients). This was a single-center study. The substance P cutoff for high versus low was not clearly defined. The study only looked at the first chemotherapy cycle."},{"rthcId":"RPEP-05669","title":"Targeted Delivery of Cabazitaxel Using Cyclic Cell-Penetrating Peptide and Biomarkers of Extracellular Matrix for Prostate and Breast Cancer Therapy.","authors":"Park, Shang Eun; El-Sayed, Naglaa Salem; Shamloo, Kiumars; Lohan, Sandeep; Kumar, Sumit; Sajid, Muhammad Imran; Tiwari, Rakesh Kumar","year":2021,"journal":"Bioconjugate chemistry, 32(8), 1898-1914","doi":"10.1021/acs.bioconjchem.1c00319","pmid":"34309357","tags":["cell-penetrating","cancer","peptide-delivery","cyclic-peptides"],"studyType":"basic-research","evidenceStrength":"preliminary","keyFinding":"Two peptide-drug conjugates were created: TP1-cCPP-CBT (targeting integrins) and TP2-cCPP-CBT (targeting extradomain B of fibronectin). Both markers are overexpressed on prostate and breast cancer cells.\n\nThe conjugates showed 3-4 fold less antiproliferative activity against cancer cells compared to a cabazitaxel analog (CBT-GA). This modest loss of potency was offset by a dramatic improvement in safety: the conjugates were 31-34 fold less toxic to normal human embryonic kidney (HEK-293) cells.\n\nFlow cytometry and confocal microscopy confirmed that the conjugates selectively accumulated in cancer cells overexpressing the target biomarkers. Stability studies showed the conjugates held up in human plasma and released the drug under the acidic and reducing conditions found inside tumors.","whyItMatters":"Chemotherapy drugs like cabazitaxel are effective but toxic to healthy tissue. Peptide-drug conjugates that selectively deliver the drug to cancer cells could reduce side effects. The 31-34 fold reduction in toxicity to normal cells is a significant improvement.","specificNumbers":"3-4x less potent vs cancer cells; 31-34x less toxic to normal cells; RGDC and CTVRTSAD targeting peptides","methodology":"Researchers synthesized peptide-drug conjugates linking cabazitaxel to cyclic cell-penetrating peptides via an acid-sensitive ester bond, with targeting peptides attached via disulfide bonds. They tested antiproliferative activity on cancer cell lines and normal HEK-293 cells, measured uptake by flow cytometry and confocal microscopy, and assessed stability in human plasma and at different pH and redox conditions.","limitations":"All testing was done in cell lines, not animals or humans. The 3-4 fold loss of potency against cancer cells is a tradeoff that would need to be overcome for clinical use. Only two cancer biomarkers were tested. In vivo pharmacokinetics, biodistribution, and tumor shrinkage were not assessed."},{"rthcId":"RPEP-05670","title":"Comparative risk of musculoskeletal adverse reactions among new users of dipeptidyl peptidase-4 inhibitors: A retrospective cohort study.","authors":"Park, Taehwan; Bresnahan, Maureen; Griggs, Scott K; Chen, Jiajing; Cho, Alex H; Gousse, Yolene; Feinglos, Mark","year":2021,"journal":"Exploratory research in clinical and social pharmacy, 2, 100022","doi":"10.1016/j.rcsop.2021.100022","pmid":"35481118","tags":["glp-1","diabetes","side-effects","peptide-safety"],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"After propensity score matching, the hazard ratio for musculoskeletal conditions among DPP-4 inhibitor users versus non-DPP-4 inhibitor users was 1.01 (95% CI 0.97-1.05), meaning essentially no difference.\n\nWhen compared to specific drug classes individually, DPP-4 inhibitors had similar musculoskeletal risk as metformin, sulfonylureas, meglitinides, and GLP-1 receptor agonists.\n\nThe only exception was thiazolidinediones (like pioglitazone), whose users had slightly higher musculoskeletal risk than DPP-4 inhibitor users (HR 1.05, 95% CI 1.00-1.10). This suggests the joint pain signal may actually come from thiazolidinediones rather than DPP-4 inhibitors.\n\nDPP-4 (dipeptidyl peptidase-4) is an enzyme that breaks down peptide hormones like GLP-1 and GIP. DPP-4 inhibitors (sitagliptin, saxagliptin, etc.) block this enzyme to keep these hormones active longer.","whyItMatters":"Reports of joint pain associated with DPP-4 inhibitors prompted FDA safety communications. This large real-world study provides reassurance that DPP-4 inhibitors do not meaningfully increase musculoskeletal risk compared to other diabetes drugs.","specificNumbers":"HR 1.01 (95% CI 0.97-1.05) for MSk conditions; thiazolidinediones slightly higher HR 1.05","methodology":"Retrospective cohort study using a national claims database (2007-2014). New users of DPP-4 inhibitors were propensity-score matched to new users of other diabetes drugs (metformin, sulfonylureas, thiazolidinediones, meglitinides, GLP-1 RAs). Outcomes were new diagnoses of arthralgia, arthropathy, or inflammatory arthritis. Cox regression estimated hazard ratios.","limitations":"Claims data cannot capture undiagnosed joint pain or pain that patients did not seek care for. The study could not verify that patients actually took their medications. Residual confounding is possible despite propensity matching. The follow-up period and specific DPP-4 inhibitor drugs used were not detailed in the abstract."},{"rthcId":"RPEP-05671","title":"Conditional Inactivation of Limbic Neuropeptide Y-1 Receptors Increases Vulnerability to Diet-Induced Obesity in Male Mice.","authors":"Paterlini, Silvia; Panelli, Riccardo; Gioiosa, Laura; Parmigiani, Stefano; Franceschini, Paolo; Bertocchi, Ilaria; Oberto, Alessandra; Bartolomucci, Alessandro; Eva, Carola; Palanza, Paola","year":2021,"journal":"International journal of molecular sciences, 22(16)","doi":"10.3390/ijms22168745","pmid":"34445453","tags":["neuropeptides","weight-loss","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Mice lacking NPY Y1 receptors in their limbic forebrain neurons (Npy1rrfb mice) were fed a high-fat diet for 3 weeks. Compared to normal mice on the same diet, they showed:\n\n- Increased body weight gain\n- More visceral (belly) fat\n- Higher blood glucose levels\n- Hyperphagia (overeating)\n- Dysregulated calorie intake\n\nThe researchers had previously shown these same mice had lower baseline body weight and higher anxiety. So the Y1 receptor in the limbic system appears to play a dual role: it helps regulate both emotional state and the body's response to high-calorie food.\n\nThe finding suggests that limbic Y1 receptors are needed for the brain to properly adjust eating behavior when calorie-rich food is available. Without them, the mice cannot habituate to high-fat food and overeat.","whyItMatters":"NPY is one of the most powerful appetite-stimulating peptides in the brain, and its Y1 receptor mediates many of those effects. This study shows the limbic Y1 receptor specifically controls how the brain responds to high-fat food. It provides a neuroanatomical explanation for how emotional brain circuits influence obesity risk.","specificNumbers":"3-week HFD; increased body weight, visceral fat, blood glucose, and food intake in knockout mice","methodology":"Researchers used a conditional knockout system to delete the Npy1r gene specifically in excitatory neurons of the forebrain/limbic areas of adolescent male mice. The knockout mice and controls were fed a high-fat diet for 3 weeks. Body weight, visceral fat, blood glucose, and food intake were measured.","limitations":"This was tested in mice, not people. Only male mice were studied. The 3-week high-fat diet is relatively short. The conditional knockout affects all limbic excitatory neurons, not specific subpopulations. The gene deletion happened during adolescence, so it is unclear whether adult deletion would have the same effect."},{"rthcId":"RPEP-05672","title":"Nonviral Expression of LL-37 in a Human Skin Equivalent to Prevent Infection in Skin Wounds.","authors":"Patiño, Maria Isabel; Restrepo, Luz Marina; Becerra, Natalia Yiset; van der Mei, Henny C; van Kooten, Theo G; Sharma, Prashant K","year":2021,"journal":"Human gene therapy, 32(19-20), 1147-1157","doi":"10.1089/hum.2021.034","pmid":"33980038","tags":["ll-37","antimicrobial-peptides","wound-healing","skin-repair"],"studyType":"basic-research","evidenceStrength":"preliminary","keyFinding":"Human skin equivalents (HSEs) were built using primary human fibroblasts and keratinocytes transfected with polyplexes (nonviral gene carriers) to express LL-37.\n\nBefore building the modified grafts, the researchers confirmed that LL-37 treatment promoted cellular proliferation in normal HSEs. The transfected HSEs then produced elevated LL-37 levels, confirmed both in the culture fluid and by local tissue staining.\n\nThe LL-37-expressing HSEs showed enhanced antimicrobial activity against S. aureus in vitro. They also maintained histological characteristics close to normal skin, meaning the genetic modification did not disrupt skin structure.\n\nTesting against P. aeruginosa (another common wound pathogen) was also performed, though the abstract emphasizes the S. aureus result.","whyItMatters":"Wound infections by antibiotic-resistant bacteria like MRSA kill thousands of patients yearly. Skin grafts that produce their own antimicrobial peptides could prevent infection without relying on antibiotics, addressing a critical gap in wound care.","specificNumbers":"Elevated LL-37 expression; S. aureus antimicrobial activity confirmed; normal histology preserved; nonviral polyplex transfection","methodology":"Primary human fibroblasts and keratinocytes were transfected using polyplexes (nonviral delivery particles) to express LL-37. These cells were used to construct human skin equivalents. LL-37 levels were measured in culture supernatants and by tissue staining. Antimicrobial activity was tested against S. aureus and P. aeruginosa. Skin structure was evaluated by histology.","limitations":"This is an in vitro study. The skin equivalents were not tested on actual wounds in animals or humans. Duration of LL-37 expression from nonviral transfection is typically short and may not last long enough for clinical wound healing. Only two bacterial species were tested. The quantitative level of LL-37 expression was not compared to natural skin levels."},{"rthcId":"RPEP-05673","title":"Neuroimmune Pathophysiology in Asthma.","authors":"Pavón-Romero, Gandhi F; Serrano-Pérez, Nancy Haydée; García-Sánchez, Lizbeth; Ramírez-Jiménez, Fernando; Terán, Luis M","year":2021,"journal":"Frontiers in cell and developmental biology, 9, 663535","doi":"10.3389/fcell.2021.663535","pmid":"34055794","tags":[],"studyType":"Review","evidenceStrength":"moderate","keyFinding":"Neuropeptides play a significant and underappreciated role in asthma beyond traditional inflammatory mechanisms. The airway epithelium contains pulmonary neuroendocrine cells that release neuropeptides including substance P (SP), neurokinin A (NKA), vasoactive intestinal peptide (VIP), CGRP, neuropeptide Y (NPY), and orphanin FQ (N/OFQ) after allergen exposure.\n\nThese neuropeptides have opposing effects: SP, NKA, and serotonin drive inflammation (promoting chemokine synthesis in eosinophils, mast cells, and neutrophils), while VIP and N/OFQ provide anti-inflammatory and bronchodilatory effects. CGRP and acetylcholine have dual roles depending on which receptor pathway is activated — for example, ACh acting on M3 receptors causes bronchoconstriction and mucus overproduction, while ACh acting on α7nAChR receptors on ILC2 cells actually reduces inflammation.\n\nExperimental NK1R/NK2R antagonists and exogenous VIP administration have decreased inflammatory mediators in studies, suggesting that targeting neuropeptide pathways could be a novel therapeutic approach for asthma.","whyItMatters":"Most asthma research focuses on immune cells and inflammatory pathways, but the nervous system's contribution through neuropeptides is often overlooked. This review shows that neuropeptides are not just bystanders — they actively drive bronchoconstriction, mucus production, and immune cell recruitment. Understanding these pathways opens up entirely new drug targets for asthma, particularly for patients who don't respond well to conventional corticosteroid therapy.","specificNumbers":"6+ neuropeptides involved · SP-NK1R axis promotes eosinophil/mast cell chemokines · VIP-VPAC1 axis = bronchodilation · CGRP-RAMP1 enhances Th2/Th9 responses · ACh-α7nAChR reduces TNF-α, IL-1, IL-6","methodology":"Narrative review published in Frontiers in Cell and Developmental Biology, synthesizing evidence on the roles of neurotransmitters and neuropeptides in asthma pathophysiology, their receptor pathways, and potential therapeutic applications.","limitations":"Narrative review without systematic search methodology. Much of the neuropeptide research in asthma comes from animal models, with limited human clinical trial data for neuropeptide-targeted therapies. The therapeutic potential of NK1R/NK2R antagonists and VIP is based largely on preclinical and early-phase studies."},{"rthcId":"RPEP-05674","title":"Net charge tuning modulates the antiplasmodial and anticancer properties of peptides derived from scorpion venom.","authors":"Pedron, Cibele Nicolaski; Silva, Adriana Farias; Torres, Marcelo Der Torossian; Oliveira, Cyntia Silva de; Andrade, Gislaine Patricia; Cerchiaro, Giselle; Pinhal, Maria Aparecida Silva; de la Fuente-Nunez, Cesar; Oliveira Junior, Vani Xavier","year":2021,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 27(4), e3296","doi":"10.1002/psc.3296","pmid":"33442881","tags":["venom-peptides","antimicrobial-peptides","cancer","peptide-design","infection"],"studyType":"basic-research","evidenceStrength":"preliminary","keyFinding":"Three arginine-substituted variants of the scorpion peptide VmCT1 were tested:\n\n- [Arg]3-VmCT1-NH2: IC50 of 0.57 µmol/L against P. gallinaceum sporozoites\n- [Arg]7-VmCT1-NH2: IC50 of 0.51 µmol/L (both potent antimalarial activity)\n- [Arg]11-VmCT1-NH2: No activity against malaria parasites\n\nThe fact that [Arg]11 lost antimalarial activity while [Arg]3 and [Arg]7 retained it shows that net charge tuning has a sweet spot. Too much positive charge can actually reduce activity against certain targets.\n\nAll three peptides showed activity against MCF-7 breast cancer cells and displayed lower toxicity toward healthy cells. This dual antimalarial and anticancer activity from simple amino acid substitutions demonstrates the versatility of venom peptide templates.","whyItMatters":"Malaria and cancer both need new treatments. Finding a single peptide scaffold that can be tuned for both activities by simple charge modifications is efficient drug discovery. The sub-micromolar antimalarial potency is especially notable.","specificNumbers":"[Arg]3 IC50=0.57µM; [Arg]7 IC50=0.51µM vs P. gallinaceum; all active vs MCF-7; [Arg]11 inactive vs malaria","methodology":"Researchers synthesized three variants of VmCT1 with single arginine substitutions at positions 3, 7, or 11. They tested antimalarial activity against P. gallinaceum sporozoites (IC50), anticancer activity against MCF-7 breast cancer cells, and cytotoxicity toward healthy cells using parasitic sensitivity and cell proliferation assays.","limitations":"P. gallinaceum is a bird malaria parasite, not human malaria (P. falciparum). Results may not translate to human malaria species. The study was entirely in vitro. MCF-7 is a single cancer cell line. No animal models were used. Pharmacokinetics and stability of these peptides were not assessed."},{"rthcId":"RPEP-05675","title":"Secondary Structural Transformation of Bovine Lactoferricin Affects Its Antibacterial Activity.","authors":"Pei, Jie; Xiong, Lin; Bao, Pengjia; Chu, Min; Yan, Ping; Guo, Xian","year":2021,"journal":"Probiotics and antimicrobial proteins, 13(3), 873-884","doi":"10.1007/s12602-020-09726-8","pmid":"33188636","tags":["antimicrobial-peptides","bioactive-food-peptides","peptide-design"],"studyType":"basic-research","evidenceStrength":"preliminary","keyFinding":"Three peptide variants were tested:\n1. bLfcin (natural, can flex between structures)\n2. bLfcin DB (locked with a disulfide bond)\n3. bLfcin C36G (mutation prevents disulfide formation)\n\nIn water, bLfcin and C36G had similar secondary structures. Under less hydrophobic conditions, bLfcin and DB had similar structures. This confirms bLfcin can switch between conformations depending on the environment.\n\nAll three killed E. coli ATCC 25922, Salmonella typhimurium, and Shigella flexneri. None were effective against S. aureus. The natural bLfcin showed higher antibacterial activity than both variants, suggesting its ability to change shape gives it an advantage when encountering different bacterial membranes.","whyItMatters":"Understanding why some antimicrobial peptides are more effective than others is essential for designing better antibiotics. This study shows that structural flexibility, not just a single fixed shape, contributes to lactoferricin's bacteria-killing ability.","specificNumbers":"3 variants; active vs E. coli, Salmonella, Shigella; inactive vs S. aureus; structure varies with ionic/hydrophobic conditions","methodology":"Researchers synthesized bLfcin and two derivatives (disulfide-bonded and C36G mutant). They used circular dichroism spectroscopy to measure secondary structure in solutions of different ionic strength and hydrophobicity. Antibacterial activity was tested against four bacterial strains using standard MIC assays.","limitations":"Only four bacterial strains were tested. The study did not examine the mechanism of killing (membrane disruption, intracellular targets, etc.). No animal or human testing was performed. The lack of activity against S. aureus limits clinical relevance, as S. aureus is a major pathogen."},{"rthcId":"RPEP-05676","title":"NanoClick: A High Throughput, Target-Agnostic Peptide Cell Permeability Assay.","authors":"Peier, Andrea; Ge, Lan; Boyer, Nicolas; Frost, John; Duggal, Ruchia; Biswas, Kaustav; Edmondson, Scott; Hermes, Jeffrey D; Yan, Lin; Zimprich, Chad; Sadruddin, Ahmad; Kristal Kaan, Hung Yi; Chandramohan, Arun; Brown, Christopher J; Thean, Dawn; Lee, Xue Er; Yuen, Tsz Ying; Ferrer-Gago, Fernando J; Johannes, Charles W; Lane, David P; Sherborne, Brad; Corona, Cesear; Robers, Matthew B; Sawyer, Tomi K; Partridge, Anthony W","year":2021,"journal":"ACS chemical biology, 16(2), 293-309","doi":"10.1021/acschembio.0c00804","pmid":"33539064","tags":["cell-penetrating","cyclic-peptides","peptide-design","bioavailability"],"studyType":"basic-research","evidenceStrength":"moderate","keyFinding":"NanoClick measures the cumulative cytosolic exposure of a peptide in a concentration-dependent manner. It combines two technologies: in-cell click chemistry (where a chemical tag on the peptide reacts with a partner inside the cell) and NanoBRET (a light signal that only fires when the peptide reaches the cytoplasm).\n\nThe assay was validated using known cell-penetrating peptides and correlated with actual cellular activity using a p53/MDM2 model system (a well-studied protein-protein interaction in cancer). This confirms NanoClick measures functionally relevant cell penetration.\n\nWith minimal changes to the peptide sequence, NanoClick can detect entry via different mechanisms: endocytosis, direct membrane translocation, or passive permeability. This versatility is important because different peptides enter cells by different routes.","whyItMatters":"Macrocyclic peptides can target protein-protein interactions that small molecules cannot reach, but they must get inside cells to work. The lack of a high-throughput permeability assay has been a critical bottleneck. NanoClick fills this gap and could accelerate peptide drug discovery significantly.","specificNumbers":"Validated with known CPPs; correlated with p53/MDM2 system; measures endocytosis, translocation, passive permeability","methodology":"Researchers developed the NanoClick assay using HeLa cells expressing NanoBRET components. They validated it with known cell-penetrating peptides and a p53/MDM2 inhibitor peptide system. The assay uses click chemistry-compatible tags added to test peptides with minimal sequence disruption. High-throughput screening capability was demonstrated.","limitations":"The assay requires adding click chemistry tags to peptides, which could subtly alter their properties. It was demonstrated primarily with cyclic peptides; performance with other peptide types may vary. The assay measures cytosolic exposure but not subcellular localization. It was validated in one cell line (HeLa)."},{"rthcId":"RPEP-05677","title":"A Review on Health-Promoting, Biological, and Functional Aspects of Bioactive Peptides in Food Applications.","authors":"Peighambardoust, Seyed Hadi; Karami, Zohreh; Pateiro, Mirian; Lorenzo, José M","year":2021,"journal":"Biomolecules, 11(5)","doi":"10.3390/biom11050631","pmid":"33922830","tags":["bioactive-food-peptides","antimicrobial-peptides","cardiovascular"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Food-derived bioactive peptides are specific protein fragments released during digestion, fermentation, or enzymatic processing. The review covers several key biological activities:\n\n- Antihypertensive: Many food peptides inhibit ACE (angiotensin-converting enzyme), which lowers blood pressure. Milk-derived peptides like VPP and IPP are the best studied.\n- Antioxidant: Peptides from fish, soy, and cereals scavenge free radicals and reduce oxidative damage.\n- Antiobesity: Some peptides affect appetite hormones and lipid metabolism.\n- Hypocholesterolemic: Certain peptides reduce cholesterol absorption or synthesis.\n- Antimicrobial: Food peptides can kill bacteria and fungi.\n\nBeyond health effects, these peptides also have functional properties in foods: water holding, solubility, emulsifying, and foaming capacity, making them useful as food additives.","whyItMatters":"Bioactive food peptides offer a natural approach to managing chronic diseases like hypertension and obesity. They can be incorporated into functional foods and nutraceuticals, bridging the gap between diet and medicine.","specificNumbers":"ACE inhibitory, antioxidant, antiobesity, antimicrobial, hypocholesterolemic activities; sources: dairy, fish, soy, marine, fermented foods","methodology":"This is a narrative review surveying published literature on bioactive peptides from food sources. It covers biological activities (antihypertensive, antioxidant, antiobesity, antimicrobial) and functional food properties.","limitations":"This is a broad review without new experimental data. Many food peptide health claims are based on in vitro or animal studies, not human clinical trials. The doses needed for clinical effects often exceed what normal food consumption provides. Bioavailability of food peptides through the gut is often unclear."},{"rthcId":"RPEP-05678","title":"Role of a Dual Glucose-Dependent Insulinotropic Peptide (GIP)/Glucagon-like Peptide-1 Receptor Agonist (Twincretin) in Glycemic Control: From Pathophysiology to Treatment.","authors":"Pelle, Maria Chiara; Provenzano, Michele; Zaffina, Isabella; Pujia, Roberta; Giofrè, Federica; Lucà, Stefania; Andreucci, Michele; Sciacqua, Angela; Arturi, Franco","year":2021,"journal":"Life (Basel, Switzerland), 12(1)","doi":"10.3390/life12010029","pmid":"35054422","tags":["tirzepatide","glp-1","diabetes","weight-loss"],"studyType":"review","evidenceStrength":"strong","keyFinding":"GLP-1 and GIP are both incretin hormones released from the gut after eating, but they have different effects:\n\n- GLP-1 strongly stimulates insulin and suppresses appetite\n- GIP has weak insulin effects alone and may actually promote fat storage\n- In type 2 diabetes, GIP receptors on pancreatic beta cells are downregulated by high blood sugar, reducing GIP's effectiveness\n\nHowever, when GIP and GLP-1 are combined in a single molecule (tirzepatide), they produce synergistic effects: stronger insulin release, better glucagon suppression, and enhanced weight loss compared to either hormone alone.\n\nThe glucagonotropic effect of GIP (stimulating glucagon) persists even in diabetes, which initially seemed problematic. But the combined molecule manages to overcome this through the dominant GLP-1 effect.\n\nPreclinical and Phase 1-3 clinical trials showed tirzepatide produced potent glucose lowering and weight loss within an acceptable safety profile.","whyItMatters":"Tirzepatide has become one of the most important new diabetes and weight loss drugs. Understanding why combining GIP and GLP-1 works better than GLP-1 alone helps explain its superior clinical results and guides future multi-agonist drug development.","specificNumbers":"Tirzepatide 5/10/15 mg weekly; dual GIP/GLP-1 activation; synergistic insulin and weight effects; Phase 1-3 data","methodology":"This is a narrative review covering the physiology of GIP and GLP-1, the rationale for dual agonism, and the clinical trial results for tirzepatide from preclinical through Phase 3.","limitations":"This is a review article without new data. The understanding of GIP's role in obesity is still evolving and somewhat contradictory (it may promote or reduce fat storage depending on context). Long-term cardiovascular outcome data for tirzepatide were not yet available at publication. The review does not deeply address side effects."},{"rthcId":"RPEP-05679","title":"Immunological Aspects of SARS-CoV-2 Infection and the Putative Beneficial Role of Vitamin-D.","authors":"Peng, Ming-Yieh; Liu, Wen-Chih; Zheng, Jing-Quan; Lu, Chien-Lin; Hou, Yi-Chou; Zheng, Cai-Mei; Song, Jenn-Yeu; Lu, Kuo-Cheng; Chao, You-Chen","year":2021,"journal":"International journal of molecular sciences, 22(10)","doi":"10.3390/ijms22105251","pmid":"34065735","tags":["ll-37","antimicrobial-peptides","immune-function","infection","respiratory"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Vitamin D acts on both innate and adaptive immunity in ways relevant to COVID-19:\n\nInnate immunity: Vitamin D activates Toll-like receptor 2, promotes cathelicidin (LL-37) and beta-defensin expression, stimulates autophagy (cellular self-cleaning), and increases lysosomal enzyme production in macrophages.\n\nAdaptive immunity: Vitamin D enhances CD4+ T cells, suppresses Th17 cells (which drive harmful inflammation), and promotes virus-specific antibody production.\n\nCytokine storm prevention: Vitamin D reduces pro-inflammatory cytokine release from CD4+ T cells through NF-kB signaling, potentially preventing the deadly cytokine storms seen in severe COVID-19.\n\nACE2 regulation: Vitamin D increases ACE2 expression. While SARS-CoV-2 uses ACE2 to enter cells, higher ACE2 levels may actually trap and inactivate the virus. Vitamin D also inhibits the renin-angiotensin system, reducing the tissue damage, inflammation, and organ failure associated with severe infection.\n\nMultiple observational studies show inverse correlations between vitamin D levels and COVID-19 severity.","whyItMatters":"The connection between vitamin D and antimicrobial peptide production has been known for years. This review applies that biology to COVID-19, providing a comprehensive mechanism for how vitamin D could reduce disease severity through multiple pathways including LL-37 and defensin upregulation.","specificNumbers":"Vitamin D upregulates LL-37, beta-defensin, TLR2; suppresses Th17, NF-kB; increases ACE2; inverse correlation with COVID severity","methodology":"This is a narrative review synthesizing evidence from immunology studies, vitamin D biology research, and COVID-19 observational studies. It applies Hill's causality criteria to assess the strength of the vitamin D-COVID-19 connection.","limitations":"This is a review based largely on observational data and mechanistic reasoning. Observational studies cannot prove causation (sicker people may have lower vitamin D for reasons unrelated to COVID-19). Randomized trials of vitamin D for COVID-19 have shown mixed results. The review speculates about optimal dosing without trial evidence. The ACE2 hypothesis is theoretically sound but not experimentally confirmed for COVID-19."},{"rthcId":"RPEP-05680","title":"Interleukin-6 and Outcomes in Acute Heart Failure: An ASCEND-HF Substudy.","authors":"Perez, Antonio L; Grodin, Justin L; Chaikijurajai, Thanat; Wu, Yuping; Hernandez, Adrian F; Butler, Javed; Metra, Marco; Felker, G Michael; Voors, Adriaan A; McMurray, John J; Armstrong, Paul W; O'Connor, Christopher; Starling, Randall C; Tang, W H Wilson","year":2021,"journal":"Journal of cardiac failure, 27(6), 670-676","doi":"10.1016/j.cardfail.2021.01.006","pmid":"33497809","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05681","title":"A skeleton in the cupboard in ghrelin research: Where are the skinny dwarfs?","authors":"Peris-Sampedro, Fiona; Le May, Marie V; Stoltenborg, Iris; Schéle, Erik; Dickson, Suzanne L","year":2021,"journal":"Journal of neuroendocrinology, 33(11), e13025","doi":"10.1111/jne.13025","pmid":"34427011","tags":["ghrp","mk-677","hormone-optimization","receptor-signaling"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Studies delivering ghrelin or ghrelin receptor agonists show powerful effects on feeding, growth hormone secretion, and glucose homeostasis. These functions seem essential for life.\n\nYet multiple mouse models with depleted ghrelin signaling (ghrelin knockouts, ghrelin receptor knockouts, and ghrelin cell ablation) show remarkably mild phenotypes. The mice are not markedly underweight, not growth-impaired, and do not have severe metabolic problems under normal conditions.\n\nThe review explores several explanations: redundant pathways that compensate for ghrelin loss, developmental compensation (the body adjusts during growth), and the possibility that ghrelin is more important for stress responses and unusual conditions than for day-to-day function.\n\nSome phenotypes do emerge under specific challenges, such as caloric restriction, aging, or high-fat diet exposure, suggesting ghrelin's role is context-dependent rather than constitutive.","whyItMatters":"Ghrelin receptor agonists (like MK-677/ibutamoren) are widely used to boost growth hormone. Understanding why removing ghrelin has such mild effects helps calibrate expectations about what ghrelin-targeting drugs actually do and reveals the complexity of appetite and growth regulation.","specificNumbers":"Ghrelin KO, GHSR KO, ghrelin cell ablation models all show mild phenotypes; challenge-dependent effects emerge","methodology":"Systematic review of published phenotype data from mouse models with depleted ghrelin signaling, including ghrelin knockout, ghrelin receptor (GHSR) knockout, and ghrelin cell ablation models. The review compares knockout phenotypes to the effects of exogenous ghrelin administration.","limitations":"This is a review of mouse data. Mouse physiology differs from human in important ways for metabolism and growth. The review focuses on constitutive knockouts, which allow developmental compensation. Conditional adult knockouts might reveal stronger phenotypes. The \"challenge-dependent\" phenotypes make it hard to define ghrelin's exact role."},{"rthcId":"RPEP-05682","title":"Rimegepant: acute treatment for migraine headaches.","authors":"Peters, Golden L; Hennessey, Erin K","year":2021,"journal":"Pain management, 11(3), 259-266","doi":"10.2217/pmt-2020-0090","pmid":"33550872","tags":["neuropeptides","pain"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Rimegepant is a small molecule that blocks the CGRP receptor. It was developed based on the improved understanding of migraine as a neurovascular condition involving vasoactive peptides, particularly CGRP.\n\nIt is approved for acute treatment of migraine in adults with or without aura. In clinical trials, it decreased pain and reduced symptoms associated with migraine attacks.\n\nRimegepant is part of a wave of new migraine treatments in the past 3 years that includes:\n- Acute treatments: lasmiditan, rimegepant, ubrogepant\n- Preventive treatments: erenumab, fremanezumab, galcanezumab, eptinezumab\n\nAll of these target the neurovascular migraine pathway, with CGRP being the central peptide involved.","whyItMatters":"Most acute migraine treatments have been triptans, which do not work for everyone and are contraindicated in some patients with cardiovascular disease. CGRP receptor antagonists like rimegepant offer a new mechanism with a different safety profile, expanding options for migraine sufferers.","specificNumbers":"Rimegepant 75 mg oral; FDA-approved for acute and preventive migraine; CGRP receptor antagonist","methodology":"This is a narrative review covering the pharmacology, clinical evidence, and place in therapy of rimegepant for acute migraine treatment.","limitations":"This is a brief review without new clinical data. It does not deeply compare rimegepant to ubrogepant or triptans. Long-term safety data are still accumulating. Cost and insurance coverage remain barriers for many patients."},{"rthcId":"RPEP-05683","title":"Dissection of phospholipases A2 reveals multifaceted peptides targeting cancer cells, Leishmania and bacteria.","authors":"Peña-Carrillo, Maria S; Pinos-Tamayo, Edgar A; Mendes, Bruno; Domínguez-Borbor, Cristobal; Proaño-Bolaños, Carolina; Miguel, Danilo C; Almeida, José R","year":2021,"journal":"Bioorganic chemistry, 114, 105041","doi":"10.1016/j.bioorg.2021.105041","pmid":"34130109","tags":["venom-peptides","antimicrobial-peptides","cancer","peptide-design","infection"],"studyType":"basic-research","evidenceStrength":"preliminary","keyFinding":"Three biomimetic peptides (pCergo, pBmTxJ, pBmje) were designed from different regions of Asp49 phospholipase A2 proteins using bioinformatics tools (AntiCP, AMPA, PepDraw, ToxinPred, HemoPI). The peptides were 12-17 amino acids long.\n\nResults varied by target:\n- pBmje: moderate cytotoxicity against MCF-7 breast cancer cells (EC50 = 464.85 µM)\n- pBmTxJ: antibacterial against S. aureus (MIC = 37.5 µM)\n- pCergo: antibacterial against E. coli (MIC = 75 µM)\n- pCergo: antileishmanial activity against L. braziliensis (EC50 = 93.69 µM) and L. amazonensis (EC50 = 110.40 µM)\n\nThe computational design pipeline successfully predicted peptides with low toxicity and no hemolysis, confirming the utility of bioinformatics-guided peptide design.","whyItMatters":"Snake venom phospholipases are too toxic for direct use but contain structural motifs that interact with cell membranes. Extracting short peptide fragments and computationally screening for safety creates a pipeline for discovering new anti-infective and anticancer agents from natural toxins.","specificNumbers":"pBmje EC50=464.85µM vs MCF-7; pBmTxJ MIC=37.5µM vs S. aureus; pCergo MIC=75µM vs E. coli; pCergo EC50=93.69µM vs L. braziliensis","methodology":"Researchers selected short amino acid sequences from three Asp49 PLA2 proteins using a combination of five bioinformatics tools that predict antimicrobial activity, toxicity, and hemolysis. Selected peptides were synthesized, purified, and tested against MCF-7 cancer cells, bacteria (S. aureus, E. coli), and Leishmania promastigotes. Toxicity to macrophages was also assessed.","limitations":"All testing was in vitro. The anticancer EC50 (465 µM) is high, suggesting weak activity. The antibacterial MICs are moderate. No animal models were used. The computational predictions, while useful, do not guarantee success in vivo. Only a few target organisms were tested."},{"rthcId":"RPEP-05684","title":"Expression of epidermal antimicrobial peptides is increased in tinea pedis.","authors":"Pham, Christina Van Anh; Rademacher, Franziska; Hinrichs, Heilwig; Beck-Jendroschek, Vera; Harder, Melanie; Brasch, Jochen; Gläser, Regine; Harder, Jürgen","year":2021,"journal":"Mycoses, 64(7), 763-770","doi":"10.1111/myc.13279","pmid":"33797129","tags":["antimicrobial-peptides","skin-repair","infection"],"studyType":"observational","evidenceStrength":"preliminary","keyFinding":"In tinea pedis patients, antimicrobial peptide concentrations were higher in lesional (infected) skin than in non-lesional skin on the other foot and in healthy control skin. Specifically:\n\n- Human beta-defensin-2 (hBD-2) was significantly elevated\n- Psoriasin (S100A7) was significantly elevated\n- RNase 7 was also measured but the abstract emphasizes hBD-2 and psoriasin\n\nThe elevated AMP levels show that the skin's innate immune system is responding to the dermatophyte infection. The fungi appear to directly trigger AMP production, and inflammation may amplify this response.\n\nHowever, the key paradox is that these elevated defenses fail to clear the infection. The authors note there is no defect in AMP expression or induction; the dermatophytes simply resist the antimicrobial peptides. Why they survive despite elevated AMP levels remains unknown.","whyItMatters":"Athlete's foot is the most common fungal infection worldwide and is often chronic or recurrent. Understanding why the skin's natural antimicrobial peptides fail to clear dermatophytes could reveal new treatment approaches.","specificNumbers":"hBD-2 and psoriasin significantly elevated in lesional skin; 13 patients with KOH/culture/molecular-confirmed tinea pedis","methodology":"Skin scales were obtained from 13 patients with confirmed tinea pedis (diagnosed by KOH mount, culture, and molecular analysis). Lesional foot skin was rinsed with buffer and analyzed by ELISA for RNase 7, hBD-2, and psoriasin. Controls included: unaffected foot of the same patient, forearm and forehead skin of the patient, and age/gender-matched healthy volunteers.","limitations":"Only 13 patients were studied, which is a small sample. The study measured AMP levels but did not test whether these specific concentrations can kill dermatophytes in lab conditions. The comparison with healthy controls was limited by the small matched group. No longitudinal follow-up was performed to see if AMP levels change with treatment."},{"rthcId":"RPEP-05685","title":"Angler Peptides: Macrocyclic Conjugates Inhibit p53:MDM2/X Interactions and Activate Apoptosis in Cancer Cells.","authors":"Philippe, Grégoire J-B; Mittermeier, Anna; Lawrence, Nicole; Huang, Yen-Hua; Condon, Nicholas D; Loewer, Alexander; Craik, David J; Henriques, Sónia T","year":2021,"journal":"ACS chemical biology, 16(2), 414-428","doi":"10.1021/acschembio.0c00988","pmid":"33533253","tags":["cell-penetrating","cyclic-peptides","cancer","peptide-delivery"],"studyType":"basic-research","evidenceStrength":"preliminary","keyFinding":"KD3 is a potent peptide that blocks the p53-MDM2 and p53-MDMX interactions (which cancer cells use to shut down p53 tumor suppression), but KD3 cannot get inside cells on its own.\n\nTwo \"angler peptide\" conjugates succeeded:\n- cTAT-KD3: entered via endocytosis, escaped endosomes, activated p53 at 1-12 µM across MCF7 (breast), A549 (lung), and HCT116 (colon) cancer cells\n- cR10-KD3: entered via direct membrane translocation, activated p53 at just 1 µM in all three cell lines\n\nThe direct translocation pathway (cR10-KD3) was clearly superior: less toxic, more efficient delivery at lower concentrations, and less dependent on cell membrane type. The endocytic pathway (cTAT-KD3) required higher concentrations and varied more between cell lines.\n\nThis demonstrates that non-permeable peptide drug candidates can be rescued by conjugation to cell-penetrating peptides, expanding the pool of usable anticancer peptides.","whyItMatters":"The p53 pathway is disrupted in most cancers. Peptides that block p53-MDM2 interactions are potent in the test tube but useless if they cannot get inside cells. The angler peptide strategy solves this delivery problem and could be applied to many other non-permeable anticancer peptides.","specificNumbers":"cR10-KD3 active at 1µM; cTAT-KD3 active at 1-12µM; 3 cancer cell lines; direct translocation superior","methodology":"Researchers conjugated KD3 to a panel of cyclic cell-penetrating peptides. They measured binding affinity for MDM2/MDMX, cellular uptake mechanisms (endocytosis vs translocation), p53 pathway activation, and apoptosis in three cancer cell lines. Hemolysis and toxicity to normal blood cells were also assessed.","limitations":"All testing was in cancer cell lines, not animals or humans. The study did not test whether angler peptides shrink tumors in vivo. Stability in blood and pharmacokinetics were not assessed. The hemolysis data were favorable, but full toxicity profiling in animals is needed."},{"rthcId":"RPEP-05686","title":"Simplified Theta-defensin [Ser3,7,12,16] RTD-2 Analog Is Involved in Proteasomal Degradation Pathway in Breast Cancer.","authors":"Pianka, Joanna; Gruba, Natalia; Kitowska, Kamila; Mieczkowski, Kamil; Wysocka, Magdalena; Sądej, Rafał; Lesner, Adam","year":2021,"journal":"Anticancer research, 41(11), 5415-5423","doi":"10.21873/anticanres.15353","pmid":"34732410","tags":["antimicrobial-peptides","cancer","cyclic-peptides","peptide-design"],"studyType":"basic-research","evidenceStrength":"preliminary","keyFinding":"The [Ser3,7,12,16]-RTD-2 analog, where four cysteines were replaced with serines to simplify the structure, selectively targeted various breast cancer cell types.\n\nImmunoprecipitation studies identified eleven proteins that the peptide interacted with in both MDA-MB-231 (triple-negative) and T47D (hormone receptor-positive) breast cancer cell lines. These proteins were primarily nuclear and strongly connected to the proteasomal protein degradation pathway.\n\nThe ubiquitin-proteasome system is markedly increased in breast cancer patients. Proteasome inhibitors (like bortezomib) are already used in blood cancers. This study suggests that defensin-based peptides could offer a new way to modulate this system in breast cancer specifically.","whyItMatters":"Theta-defensins are circular antimicrobial peptides found in some primates. Showing that a simplified version can target the proteasome pathway in breast cancer opens a new connection between innate immune peptides and cancer biology.","specificNumbers":"[Ser3,7,12,16]-RTD-2; 11 interacting proteins in both cell lines; proteasome pathway involvement","methodology":"RTD-2 analogs were synthesized by solid-phase peptide synthesis. Cell viability was measured by MTT assay. Immunoprecipitation identified molecular partners of the peptide in MDA-MB-231 and T47D breast cancer cell lines.","limitations":"Only two breast cancer cell lines were tested for protein interactions. The study identified interacting proteins but did not prove the peptide directly inhibits the proteasome. The selectivity claim needs validation across more normal cell types. No animal testing was performed."},{"rthcId":"RPEP-05687","title":"Priming With Toll-Like Receptor 3 Agonist Poly(I:C) Enhances Content of Innate Immune Defense Proteins but Not MicroRNAs in Human Mesenchymal Stem Cell-Derived Extracellular Vesicles.","authors":"Pierce, Lisa M; Kurata, Wendy E","year":2021,"journal":"Frontiers in cell and developmental biology, 9, 676356","doi":"10.3389/fcell.2021.676356","pmid":"34109180","tags":["antimicrobial-peptides","immune-function","peptide-delivery"],"studyType":"basic-research","evidenceStrength":"preliminary","keyFinding":"Poly(I:C) priming of MSCs resulted in 49 upregulated EV proteins. Of these, 21 are known to be important in host defense and innate immunity.\n\nFunctional analysis revealed enrichment in complement and coagulation cascades, acute phase response, innate immunity, and S. aureus infection pathways.\n\nSeveral antimicrobial peptides were found in EVs at baseline and remained unchanged by priming: dermcidin, lactoferrin, lipocalin 1, lysozyme C, neutrophil defensin 1, psoriasin (S100A7), calprotectin (S100A8/A9), and histone H4.\n\nIn contrast to protein changes, EV microRNA content was not significantly altered by poly(I:C) priming. This means the enhanced antimicrobial function of primed EVs comes from protein cargo, not from regulatory RNA.","whyItMatters":"MSC-derived EVs are being developed as cell-free therapies for infection and inflammation. Understanding how to enhance their antimicrobial properties through priming could improve their therapeutic potential. The finding that proteins, not miRNAs, drive the enhanced function directs future research.","specificNumbers":"49 upregulated proteins; 21 defense-related; baseline AMPs: defensin 1, lactoferrin, lysozyme, psoriasin, calprotectin; miRNA unchanged","methodology":"Human bone marrow-derived MSCs were cultured with or without 1 µg/ml poly(I:C) for 1 hour. After 64 hours, EVs were collected from conditioned media. Proteomic profiling (mass spectrometry) and small RNA sequencing compared primed vs unprimed EV content.","limitations":"This is an in vitro study. The enhanced protein profile has not been tested for actual antimicrobial function. The baseline antimicrobial peptides were not changed by priming, so the specific functional contribution of the 21 new proteins needs validation. Only one priming concentration and time point were tested."},{"rthcId":"RPEP-05688","title":"Designing Chimeric Peptides: A Powerful Tool for Enhancing Antibacterial Activity.","authors":"Pineda-Castañeda, Héctor Manuel; Huertas-Ortiz, Kevin Andrey; Leal-Castro, Aura Lucía; Vargas-Casanova, Yerly; Parra-Giraldo, Claudia Marcela; García-Castañeda, Javier Eduardo; Rivera-Monroy, Zuly Jenny","year":2021,"journal":"Chemistry & biodiversity, 18(2), e2000885","doi":"10.1002/cbdv.202000885","pmid":"33369144","tags":["antimicrobial-peptides","bioactive-food-peptides","peptide-design"],"studyType":"basic-research","evidenceStrength":"preliminary","keyFinding":"All chimeric peptides showed greater antibacterial activity than the individual lactoferricin or buforin II sequences they were built from. The most important design finding was that the palindromic motif RLLRRLLR was the most relevant sequence for antibacterial activity.\n\nThree key design rules emerged:\n1. The linked sequences determine activity; the RLLRRLLR motif was most important\n2. Adding a spacer between the two parent sequences enhanced activity against both Gram-positive and Gram-negative bacteria without complicating synthesis\n3. Replacing arginine with lysine in the parent sequences simplified synthesis without significantly reducing antibacterial potency\n\nThe most active chimera for each bacterial strain showed either bacteriostatic (growth-stopping) or bactericidal (bacteria-killing) effects depending on concentration.","whyItMatters":"Combining sequences from different antimicrobial peptides is a powerful strategy for creating more effective antibiotics. This study provides practical design rules for building chimeric peptides that outperform their parent molecules.","specificNumbers":"All chimeras outperformed parents; RLLRRLLR motif key; spacer enhanced activity; Arg-to-Lys simplified synthesis","methodology":"Chimeric peptides were synthesized by solid-phase peptide synthesis (SPPS) and characterized by HPLC and mass spectrometry. Antibacterial activity was tested against Gram-positive and Gram-negative strains. Bacteriostatic vs bactericidal effects were determined at different concentrations.","limitations":"Only a limited panel of bacterial strains was tested. No animal studies or toxicity assessments were reported in the abstract. The study did not test activity against antibiotic-resistant clinical isolates. Stability and pharmacokinetics were not assessed."},{"rthcId":"RPEP-05689","title":"The effect of the ghrelin-receptor agonist capromorelin on glucose metabolism in healthy cats.","authors":"Pires, J; Greathouse, R L; Quach, N; Huising, M O; Crakes, K R; Miller, M; Gilor, C","year":2021,"journal":"Domestic animal endocrinology, 74, 106484","doi":"10.1016/j.domaniend.2020.106484","pmid":"32619812","tags":["ghrp","mk-677","hormone-optimization","diabetes"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Capromorelin activates the ghrelin receptor (GHSR), which is found on pancreatic delta cells that produce somatostatin. Activating delta cells was expected to suppress insulin secretion.\n\nOn day 1:\n- Fasting blood glucose increased by 13 mg/dL (p < 0.0001)\n- Insulin decreased (p = 0.03)\n- Glucagon was unchanged\n- First-phase insulin response (FPIR) during glucose tolerance test dropped by 72% (from 17,437 to 4,931 ng/L/15min, p = 0.004)\n\nDays 2-4:\n- Mean interstitial glucose rose by 19 mg/dL (p = 0.03)\n- Glycemic variability increased (SD 9.7 vs 5.0, p = 0.02)\n\nBy day 30:\n- Glucose tolerance returned to baseline\n- Glycemic variability normalized\n- But FPIR was still partially blunted (9,993 vs 17,437, p = 0.045)\n\nThe body appeared to compensate for the initial insulin suppression over time.","whyItMatters":"This study has implications beyond veterinary medicine. Ghrelin receptor agonists like MK-677 (ibutamoren) are widely used in human growth hormone optimization. Understanding that ghrelin receptor activation temporarily impairs insulin secretion and glucose control is important for anyone considering these compounds, particularly people with existing insulin sensitivity concerns. The finding that metabolic effects normalize over 30 days suggests an adaptation mechanism worth understanding.","specificNumbers":"Day 1: fasting glucose +13mg/dL; FPIR dropped 72%; Days 2-4: glucose +19mg/dL; Day 30: glucose tolerance normalized","methodology":"Seven healthy cats received capromorelin daily for 30 days. Intravenous glucose tolerance tests were performed on days -3 (baseline), 1, and 30 to assess insulin secretion and glucose clearance. Continuous glucose monitoring tracked interstitial glucose levels and glycemic variability. Blood samples measured fasting glucose, insulin, and glucagon at multiple time points.","limitations":"Only 7 cats were studied, which is a very small sample size. Only healthy cats were tested — diabetic, obese, or insulin-resistant cats might respond differently or not adapt as well. The 30-day treatment period may not reveal longer-term metabolic consequences. The specific mechanism by which the body compensated for insulin suppression was not fully explored. Results from cats may not directly translate to other species."},{"rthcId":"RPEP-05690","title":"A Review on the Role of Food-Derived Bioactive Molecules and the Microbiota-Gut-Brain Axis in Satiety Regulation.","authors":"Pizarroso, Nuria A; Fuciños, Pablo; Gonçalves, Catarina; Pastrana, Lorenzo; Amado, Isabel R","year":2021,"journal":"Nutrients, 13(2)","doi":"10.3390/nu13020632","pmid":"33669189","tags":["glp-1","neuropeptides","weight-loss","bioactive-food-peptides"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Three gut peptide hormones — CCK, GLP-1, and PYY — serve as the primary signaling molecules in the satiety system, released by enteroendocrine cells (EECs) in response to specific macronutrients detected through nutrient-sensing receptors. The gut microbiota directly interacts with EECs and modulates hormone release by changing the gut environment and producing metabolites. Diet shapes the microbiome, which shapes hormone release, which shapes brain appetite signals — creating the microbiota-gut-brain axis (MGBA). The review proposes that bioactive compounds exploiting these nutrient-sensing mechanisms could become functional foods or drugs for obesity.","whyItMatters":"Obesity affects over 650 million adults worldwide and current treatments are limited. Understanding the natural signaling system that controls appetite — from the food we eat to the bacteria in our gut to the hormones that tell our brain we're full — reveals multiple intervention points. Rather than targeting a single receptor (as GLP-1 drugs do), future therapies could work through functional foods that optimize the entire microbiota-gut-brain axis.","specificNumbers":"CCK, GLP-1, PYY as key satiety hormones; enteroendocrine cells; microbiota-gut-brain axis; organ-on-a-chip models","methodology":"Narrative review covering the biology of gut peptide satiety hormones (CCK, GLP-1, PYY), enteroendocrine cell nutrient-sensing mechanisms, the role of the intestinal microbiota in modulating these systems, and the microbiota-gut-brain axis. Also discusses organ-on-a-chip technology as a platform for modeling multi-organ communication and testing potential bioactive compounds.","limitations":"This is a broad conceptual review without new experimental data. Many proposed mechanisms are based on animal studies and may not translate to humans. The gut microbiome-satiety connection in humans is still poorly defined. Organ-on-a-chip technology is promising but not yet validated for predicting human appetite responses. The review doesn't address the practical challenges of designing functional foods with reliable bioactive compound delivery."},{"rthcId":"RPEP-05691","title":"Antihypertensive Peptides from Ultrafiltration and Fermentation of the Ricotta Cheese Exhausted Whey: Design and Characterization of a Functional Ricotta Cheese.","authors":"Pontonio, Erica; Montemurro, Marco; De Gennaro, Gina Valeria; Miceli, Valerio; Rizzello, Carlo Giuseppe","year":2021,"journal":"Foods (Basel, Switzerland), 10(11)","doi":"10.3390/foods10112573","pmid":"34828854","tags":["bioactive-food-peptides","cardiovascular","peptide-design"],"studyType":"basic-research","evidenceStrength":"preliminary","keyFinding":"The biotechnological protocol combined membrane ultrafiltration (to concentrate proteins from waste whey) with fermentation by a selected L. helveticus strain. The fermented product had high anti-ACE activity.\n\nPeptides responsible for the activity were identified by mass spectrometry. Their sequences overlapped with known kappa-casein antihypertensive fragments.\n\nFortified ricotta cheese results:\n- 5% fortification: a 100g portion contained approximately 30 mg of bioactive peptides\n- Significantly higher anti-ACE activity compared to control and unfermented versions\n- Moderate changes in texture (increased hardness and chewiness)\n- Decreased milk odor/taste but improved flavor persistence and sapidity\n- Microbiological quality was acceptable","whyItMatters":"Cheese whey is one of the most abundant dairy waste products. Turning it into a source of bioactive peptides creates value from waste while producing a functional food that could help manage blood pressure naturally.","specificNumbers":"~30mg bioactive peptides/100g at 5% fortification; kappa-casein fragments; L. helveticus fermentation; ACE inhibition confirmed","methodology":"Ricotta cheese exhausted whey was ultrafiltered and the protein-rich retentate was fermented with L. helveticus. Bioactive peptides were identified by nano-LC-ESI-MS/MS. The fermented retentate was spray-dried and added to ricotta cheese at 1% and 5%. Products were evaluated for microbiological, chemical, functional, textural, and sensory properties.","limitations":"Anti-ACE activity in a food product does not guarantee blood pressure reduction in people. The peptides must survive further digestion and reach the bloodstream. No human clinical trial was performed. The 30 mg per 100g serving may or may not be enough for a clinical effect. Sensory changes (increased hardness, less milk taste) could affect consumer acceptance."},{"rthcId":"RPEP-05692","title":"Colonic epithelial cathelicidin (LL-37) expression intensity is associated with progression of colorectal cancer and presence of CD8+ T cell infiltrate.","authors":"Porter, Ross J; Murray, Graeme I; Alnabulsi, Abdo; Humphries, Matthew P; James, Jacqueline A; Salto-Tellez, Manuel; Craig, Stephanie G; Wang, Ji M; Yoshimura, Teizo; McLean, Mairi H","year":2021,"journal":"The journal of pathology. Clinical research, 7(5), 495-506","doi":"10.1002/cjp2.222","pmid":"33988317","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05693","title":"Role of lipid nanocarriers for enhancing oral absorption and bioavailability of insulin and GLP-1 receptor agonists.","authors":"Poudwal, Swapna; Misra, Ambikanandan; Shende, Pravin","year":2021,"journal":"Journal of drug targeting, 29(8), 834-847","doi":"10.1080/1061186X.2021.1894434","pmid":"33620269","tags":["glp-1","oral-peptides","peptide-delivery","bioavailability","diabetes"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"The review covers several strategies for oral peptide delivery using lipid nanocarriers:\n\n- Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) protect peptides from enzymatic degradation\n- Absorption enhancers can be incorporated to improve gut membrane permeability\n- PEGylation of nanocarriers improves stability and circulation time\n- Lipidization (adding fatty acid chains to peptides) improves membrane interaction\n\nAnimal studies have shown significant hypoglycemic (blood sugar lowering) activity and safety for lipid nanocarrier-delivered insulin and GLP-1 agonists. However, translating these results to humans has been a persistent challenge.\n\nThe review also discusses the clinical status of various nanocarrier approaches for anti-diabetic peptides, noting that few have advanced to human trials.","whyItMatters":"Diabetes requires lifelong treatment, and most peptide-based therapies require injections. Making insulin and GLP-1 drugs available as pills would dramatically improve patient compliance and quality of life. Lipid nanocarriers are one of the most promising platforms for achieving this.","specificNumbers":"SLNs, NLCs, liposomes; absorption enhancers, PEGylation, lipidization; animal hypoglycemic activity confirmed; few human trials","methodology":"Narrative review of lipid nanocarrier technologies for oral delivery of insulin and GLP-1 receptor agonists, covering formulation strategies, absorption enhancement mechanisms, animal study results, and clinical development status.","limitations":"This is a review without new data. Most lipid nanocarrier work is in animal models, and human translation has been difficult. Manufacturing scalability and cost are not addressed. Regulatory pathways for nanomedicine-based oral peptides are complex and uncertain."},{"rthcId":"RPEP-05694","title":"The emerging role of heterodimerisation and interacting proteins in ghrelin receptor function.","authors":"Price, Maria L; Ley, Cameron D; Gorvin, Caroline M","year":2021,"journal":"The Journal of endocrinology, 252(1), R23-R39","doi":"10.1530/JOE-21-0206","pmid":"34663757","tags":["ghrp","mk-677","receptor-signaling","neuroprotection","hormone-optimization"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"GHSR1a (the ghrelin receptor) can interact with many other transmembrane receptors through direct physical binding (heteromerization) or signaling cross-talk. These interactions produce effects including:\n\n- Biased signaling: preferential coupling to one downstream pathway\n- G protein switching: coupling to a different G protein than normal\n- Signal suppression or enhancement\n\nThe best-established interaction is between GHSR1a and dopamine receptor D1 (DRD1). These form physical complexes that promote hippocampal memory formation and synaptic plasticity. In Alzheimer's disease, GHSR1a-DRD1 complexes decrease while GHSR1a-amyloid beta complexes increase, suggesting a pathological shift.\n\nThis explains a long-standing puzzle: why GHSR1a antagonists (blockers) failed to reduce appetite despite strong evidence that ghrelin drives hunger. The receptor interactions create signaling complexity that simple blockers cannot properly target.","whyItMatters":"Understanding why ghrelin receptor blockers failed is crucial for developing better obesity drugs. The receptor interaction data suggest that targeting specific GHSR1a heteromers rather than GHSR1a alone could be more effective. The Alzheimer's connection opens new therapeutic possibilities.","specificNumbers":"GHSR1a-DRD1 heteromers; GHSR1a-Aβ complexes in Alzheimer's; interactions with DRD2, 5-HT2C, MC3R, GPR83, OX1R","methodology":"Systematic review of published studies on GHSR1a interactions with other transmembrane proteins, including in vitro overexpression studies, co-immunoprecipitation data, BRET/FRET experiments, and physiological evidence from animal models.","limitations":"Many GHSR1a interactions have only been shown in cells overexpressing both receptors, which may not represent natural conditions. Verifying these interactions in native tissues is technically challenging and largely incomplete. The Alzheimer's connection is correlational, not causal."},{"rthcId":"RPEP-05695","title":"The Toll-Like Receptor 5 agonist flagellin prevents Non-typeable Haemophilus influenzae-induced infection in cigarette smoke-exposed mice.","authors":"Pérez-Cruz, Magdiel; Koné, Bachirou; Porte, Rémi; Carnoy, Christophe; Tabareau, Julien; Gosset, Pierre; Trottein, François; Sirard, Jean-Claude; Pichavant, Muriel; Gosset, Philippe","year":2021,"journal":"PloS one, 16(3), e0236216","doi":"10.1371/journal.pone.0236216","pmid":"33784296","tags":["antimicrobial-peptides","immune-function","respiratory","infection"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Mice chronically exposed to cigarette smoke (mimicking COPD) were infected with non-typeable H. influenzae (NTHi). Treatment with recombinant flagellin, either before or after infection, significantly reduced bacterial loads in airways, lungs, and blood.\n\nThe protection was associated with:\n- Early neutrophil recruitment to the lungs\n- Lower pro-inflammatory cytokines (less collateral damage)\n- Increased IL-22 production\n- Less inflammatory cell recruitment and lung damage\n\nBlocking IL-22 with antibodies or using IL-22 knockout mice eliminated flagellin's protective effect, proving IL-22 was essential.\n\nNotably, the antimicrobial peptides defensin-beta-2 and calgranulins were NOT involved in the protection. The benefit came from IL-22-mediated mucosal defense rather than direct antimicrobial peptide killing.","whyItMatters":"COPD exacerbations caused by bacterial infections are a leading cause of hospitalization and death. There are few effective prevention strategies. Flagellin activates innate immunity in a way that clears bacteria while reducing harmful inflammation, offering a potential new approach to preventing COPD exacerbations.","specificNumbers":"Reduced bacterial loads in airways, lungs, blood; IL-22 essential (knockout and antibody blocking); defensin-beta-2 not involved","methodology":"Mice were chronically exposed to cigarette smoke to induce COPD-like symptoms, then infected with NTHi. Flagellin was injected intraperitoneally using either prophylactic or therapeutic protocols. Bacterial counts, inflammatory cells, cytokines, IL-22, and antimicrobial peptides were measured. Anti-IL-22 blocking antibodies and IL-22 knockout mice were used to confirm the mechanism.","limitations":"This was tested in mice, not people. The cigarette smoke COPD model approximates but does not fully replicate human COPD. Flagellin was injected intraperitoneally, not given by inhalation. The long-term safety of repeated TLR5 activation is unknown. The study used a single bacterial species."},{"rthcId":"RPEP-05696","title":"Proteogenomic Analysis Unveils the HLA Class I-Presented Immunopeptidome in Melanoma and EGFR-Mutant Lung Adenocarcinoma.","authors":"Qi, Yue A; Maity, Tapan K; Cultraro, Constance M; Misra, Vikram; Zhang, Xu; Ade, Catherine; Gao, Shaojian; Milewski, David; Nguyen, Khoa D; Ebrahimabadi, Mohammad H; Hanada, Ken-Ichi; Khan, Javed; Sahinalp, Cenk; Yang, James C; Guha, Udayan","year":2021,"journal":"Molecular & cellular proteomics : MCP, 20, 100136","doi":"10.1016/j.mcpro.2021.100136","pmid":"34391887","tags":["cancer","peptide-design","immune-function"],"studyType":"basic-research","evidenceStrength":"moderate","keyFinding":"The study profiled the HLA class I immunopeptidome (all peptides displayed on cell surface immune markers) in melanoma (high tumor mutation burden) and EGFR-mutant lung adenocarcinoma (low mutation burden).\n\nSimilar numbers of peptides were identified from both cancer types, despite their different mutation rates. Key findings:\n\n- 12 variant peptides from tumor-specific mutations\n- 40 cancer germline (CG) antigen-derived peptides from a custom database of 285 CG antigens\n- Over 1,000 post-translationally modified (PTM) peptides representing 58 different PTMs\n- 44 novel peptides encoded by long noncoding RNA (lncRNA), a previously unrecognized source of cancer antigens\n\nAll key findings were validated using synthetic peptide matching and HLA binding assays. The lncRNA-derived peptides represent a completely new class of potential immunotherapy targets.","whyItMatters":"Immunotherapy works best in high-mutation cancers. Low-mutation cancers like EGFR-driven lung cancer have been harder to target. Finding abundant displayed peptides in both cancer types, plus new sources like lncRNA, expands immunotherapy targets dramatically.","specificNumbers":"12 variant peptides; 40 CG antigen peptides; 1000+ PTM peptides (58 types); 44 lncRNA peptides; validated by synthetic matching and HLA binding","methodology":"Large-scale mass spectrometry-based immunopeptidome profiling of cancer cell lines and patient samples. Databases constructed from whole-exome sequencing. De novo search algorithms used. Custom cancer germline antigen and lncRNA databases created. Key peptides validated with synthetic peptide matching and HLA binding assays.","limitations":"The study profiled cell lines and a limited number of patient samples. Not all identified peptides will be immunogenic (able to trigger an immune response). The lncRNA-derived peptides are novel and need functional validation in immune assays. Some findings may be specific to the HLA types studied."},{"rthcId":"RPEP-05697","title":"Preparation of nano-hydroxyapatite/chitosan/tilapia skin peptides hydrogels and its burn wound treatment.","authors":"Qianqian, Ouyang; Songzhi, Kong; Yongmei, Huang; Xianghong, Ju; Sidong, Li; Puwang, Li; Hui, Luo","year":2021,"journal":"International journal of biological macromolecules, 181, 369-377","doi":"10.1016/j.ijbiomac.2021.03.085","pmid":"33737190","tags":["bioactive-food-peptides","wound-healing","antimicrobial-peptides","peptide-delivery"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"The hydrogel combined three components: tilapia skin peptides (TP, bioactive peptides from fish processing waste), nanohydroxyapatite (NHA, for structural support), and chitosan (a natural antimicrobial polymer), cross-linked with tannin.\n\nThe material had a highly porous structure with interconnected pores, excellent water absorption, low hemolysis (safe for blood contact), and killed both E. coli and S. aureus.\n\nIn the rabbit partial-thickness burn model, the hydrogel:\n- Promoted epithelial and dermal regeneration\n- Reduced TNF-alpha and IL-6 (inflammatory markers)\n- Increased collagen production\n- Upregulated STAT3 (cell growth signaling)\n- Upregulated VEGF (blood vessel growth factor)\n- Was compatible with endothelial cells in culture","whyItMatters":"Burns are a major clinical challenge, and current wound dressings have limitations. Using fish processing waste (tilapia skin peptides) to create a multifunctional wound dressing that fights infection, reduces inflammation, and promotes tissue regeneration addresses multiple healing needs simultaneously.","specificNumbers":"Killed E. coli and S. aureus; reduced TNF-alpha and IL-6; increased collagen, STAT3, VEGF; porous structure with high water absorption","methodology":"NHA was synthesized by coprecipitation. Hydrogels were characterized for porosity, water absorption, hemolysis, and antimicrobial activity. Cytocompatibility was tested on endothelial cells. Burn wounds were created on New Zealand rabbits and treated with the hydrogel. Wound healing was assessed by histology, gene expression (collagen, STAT3, VEGF), and inflammatory markers (TNF-alpha, IL-6).","limitations":"This was tested in rabbits, not humans. Rabbit skin heals differently from human skin. The specific active peptide sequences from tilapia skin were not identified. The tannin cross-linker may cause issues at larger scales. Long-term effects and degradation products were not assessed."},{"rthcId":"RPEP-05698","title":"Deletion of Stim1 in Hypothalamic Arcuate Nucleus Kiss1 Neurons Potentiates Synchronous GCaMP Activity and Protects against Diet-Induced Obesity.","authors":"Qiu, Jian; Stincic, Todd L; Bosch, Martha A; Connors, Ashley M; Kaech Petrie, Stefanie; Rønnekleiv, Oline K; Kelly, Martin J","year":2021,"journal":"The Journal of neuroscience : the official journal of the Society for Neuroscience, 41(47), 9688-9701","doi":"10.1523/JNEUROSCI.0622-21.2021","pmid":"34654752","tags":["neuropeptides","weight-loss","receptor-signaling","fertility"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Kiss1ARH neurons release kisspeptin, neurokinin B (NKB), and dynorphin, and also release glutamate that excites appetite-suppressing POMC neurons and inhibits appetite-stimulating AgRP neurons.\n\nDeleting STIM1 in Kiss1 neurons increased the amplitude and duration of the slow excitatory postsynaptic potential (EPSP) and augmented synchronous calcium oscillations. It also amplified the effects of NKB.\n\nIn ovariectomized female mice on a high-fat diet, STIM1 deletion in Kiss1 neurons protected against obesity and glucose intolerance. This links reproductive neuron activity directly to metabolic protection.\n\nSTIM1 normally restrains neuronal excitability by regulating calcium channels (TRPC). Removing this brake made kisspeptin neurons fire more, which appears to boost the downstream signals that control energy balance.","whyItMatters":"This study reveals that reproductive brain circuits directly influence metabolism. Boosting kisspeptin neuron activity protected against obesity, suggesting these neurons coordinate energy balance with reproductive function. This could explain why hormonal changes (menopause, PCOS) affect weight.","specificNumbers":"Increased slow EPSP amplitude/duration; augmented Ca2+ oscillations; amplified NKB; protected from HFD obesity and glucose intolerance","methodology":"Researchers used conditional knockout to delete Stim1 specifically in Kiss1 neurons. They used optogenetics with whole-cell recording and GCaMP6 calcium imaging in brain slices to measure electrophysiology. Metabolic effects were tested in ovariectomized female mice fed a high-fat diet.","limitations":"Only female mice were tested. The conditional knockout affects STIM1 throughout development, allowing compensation. The ovariectomy model removes ovarian hormones, which may not represent all clinical scenarios. The link between enhanced neuron firing and metabolic protection is correlational within this study."},{"rthcId":"RPEP-05699","title":"Comparative Efficacy of Glucagon-like Peptide 1 Receptor Agonists and Sodium Glucose Cotransporter 2 Inhibitors for Prevention of Major Adverse Cardiovascular Events in Type 2 Diabetes: A Network Meta-analysis.","authors":"Qiu, Mei; Ding, Liang-Liang; Wei, Xu-Bin; Liu, Shu-Yan; Zhou, Hai-Rong","year":2021,"journal":"Journal of cardiovascular pharmacology, 77(1), 34-37","doi":"10.1097/FJC.0000000000000916","pmid":"33136765","tags":["semaglutide","liraglutide","glp-1","cardiovascular","kidney","diabetes"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"The network meta-analysis compared multiple GLP-1 RAs and SGLT2 inhibitors head-to-head through their shared placebo comparators:\n\nDiabetes + cardiovascular disease:\n- Albiglutide (HR 0.76, p significant) and subcutaneous semaglutide (HR 0.71, p significant) ranked highest (SUCRA)\n- Both significantly better than lixisenatide\n\nDiabetes + heart failure:\n- Albiglutide ranked highest, significantly better than dapagliflozin (HR 0.69) and exenatide (HR 0.72)\n\nDiabetes + chronic kidney disease:\n- Canagliflozin and liraglutide ranked highest, both significantly better than exenatide (HR 0.72) and lixisenatide (HR 0.68/0.72)\n\nThis is the first network meta-analysis to rank these drugs across specific cardiorenal subgroups, providing guidance for personalized prescribing.","whyItMatters":"Clinicians must choose between many GLP-1 and SGLT2 drugs for patients with diabetes and heart or kidney disease. This analysis provides the first comparative ranking, showing the best drug depends on which comorbidity the patient has.","specificNumbers":"CVD: semaglutide HR 0.71, albiglutide 0.76; HF: albiglutide HR 0.69 vs dapa; CKD: canagliflozin/liraglutide HR 0.68-0.72","methodology":"Bayesian network meta-analysis of randomized cardiovascular outcome trials identified from PubMed and Embase. SUCRA (surface under the cumulative ranking curve) values were calculated to rank drugs. Hazard ratios and 95% CIs were the effect measures. Results stratified by cardiovascular disease, heart failure, and chronic kidney disease subgroups.","limitations":"Network meta-analyses rely on indirect comparisons, which are less reliable than head-to-head trials. The individual trials had different patient populations, follow-up periods, and baseline characteristics. Albiglutide is no longer commercially available. The analysis did not account for cost, side effects, or dosing convenience."},{"rthcId":"RPEP-05700","title":"The Multifaceted Mas-Related G Protein-Coupled Receptor Member X2 in Allergic Diseases and Beyond.","authors":"Quan, Paola Leonor; Sabaté-Brescó, Marina; Guo, Yanru; Martín, Margarita; Gastaminza, Gabriel","year":2021,"journal":"International journal of molecular sciences, 22(9)","doi":"10.3390/ijms22094421","pmid":"33922606","tags":["neuropeptides","antimicrobial-peptides","immune-function","receptor-signaling","inflammation"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"MRGPRX2 on mast cells recognizes an unusually diverse set of ligands:\n\nNatural ligands: host defense peptides, substance P, VIP, eosinophil granule proteins\nDrug ligands: compound 48/80, mastoparan (bee venom), quinolone antibiotics, neuromuscular blockers, morphine, vancomycin\n\nIn host defense, the mouse homolog Mrgprb2 helps mast cells detect bacterial peptides and release antimicrobial peptides and immune mediators.\n\nIn disease:\n- MRGPRX2 is linked to non-IgE drug hypersensitivity reactions (explaining why some people react to certain drugs without allergies)\n- Implicated in asthma, atopic dermatitis, contact dermatitis, and chronic spontaneous urticaria\n- May play a role in chronic inflammation through persistent mast cell activation\n- Also involved in tissue homeostasis and repair","whyItMatters":"Understanding MRGPRX2 explains why certain drugs cause allergic-like reactions without involving IgE antibodies. It also reveals how neuropeptides like substance P trigger mast cells in pain, itch, and inflammation, connecting the nervous and immune systems.","specificNumbers":"Ligands: substance P, VIP, defensins, quinolones, morphine, vancomycin, neuromuscular blockers; disease links: urticaria, asthma, dermatitis","methodology":"Comprehensive narrative review of MRGPRX2 biology covering its ligands, signaling, and roles in physiology and disease. Includes evidence from human, mouse, and rat studies.","limitations":"Much MRGPRX2 research uses cell lines with overexpressed receptors, which may not reflect natural expression levels. The human and mouse homologs have different ligand profiles. Clinical evidence for MRGPRX2 in specific diseases is still mostly correlational."},{"rthcId":"RPEP-05701","title":"Macronutrient intake, appetite, food preferences and exocrine pancreas function after treatment with short- and long-acting glucagon-like peptide-1 receptor agonists in type 2 diabetes.","authors":"Quast, Daniel R; Nauck, Michael A; Schenker, Nina; Menge, Björn A; Kapitza, Christoph; Meier, Juris J","year":2021,"journal":"Diabetes, obesity & metabolism, 23(10), 2344-2353","doi":"10.1111/dom.14477","pmid":"34189834","tags":["liraglutide","glp-1","weight-loss","diabetes"],"studyType":"randomized-controlled-trial","evidenceStrength":"moderate","keyFinding":"Both GLP-1 receptor agonists produced comparable effects on:\n- Macronutrient and energy intake (equally reduced)\n- Body weight loss\n- Appetite reduction\n\nThe key mechanistic finding was that weight loss and appetite reduction were NOT related to delayed gastric emptying or GI side effects (p > 0.05 for both). This challenges the common assumption that GLP-1 drugs reduce appetite mainly by slowing stomach emptying or causing nausea.\n\nBoth drugs improved exocrine pancreas function (faecal elastase and serum beta-carotin increased), suggesting GLP-1 drugs may benefit pancreatic enzyme output.\n\nLiraglutide specifically increased serum lipase by 18.3 U/L (p = 0.0001), while lixisenatide did not. This lipase elevation is clinically relevant because lipase rises can indicate pancreatic stress, though in this case it was associated with improved pancreatic markers overall.","whyItMatters":"Understanding how GLP-1 drugs reduce appetite is important for optimizing their use. This study shows the appetite effect is not simply caused by nausea or slow stomach emptying, suggesting a central brain mechanism. The improved pancreatic function is an unexpected bonus.","specificNumbers":"N=50; 10 weeks; equal weight/appetite reduction; liraglutide lipase +18.3 U/L (p=0.0001); no gastric emptying/GI side effect link","methodology":"Randomized trial of 50 participants assigned to lixisenatide or liraglutide for 10 weeks. Appetite, satiety, macronutrient intake, GI symptoms, gastric emptying, and pancreatic function markers were assessed at baseline and after treatment.","limitations":"With only 50 patients, the study is relatively small. The 10-week duration may not capture longer-term differences. The study was in type 2 diabetes patients and may not apply to non-diabetic weight management. Specific food preference changes were assessed but not detailed in the abstract."},{"rthcId":"RPEP-05702","title":"An overview of chia seed (Salvia hispanica L.) bioactive peptides' derivation and utilization as an emerging nutraceutical food.","authors":"Rabail, Roshina; Khan, Moazzam Rafiq; Mehwish, Hafiza Mahreen; Rajoka, Muhammad Shahid Riaz; Lorenzo, Jose Manuel; Kieliszek, Marek; Khalid, Abdur Rauf; Shabbir, Muhammad Asim; Aadil, Rana Muhammad","year":2021,"journal":"Frontiers in bioscience (Landmark edition), 26(9), 643-654","doi":"10.52586/4973","pmid":"34590473","tags":["bioactive-food-peptides","cardiovascular","diabetes"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Chia seeds are rich in high-quality protein that yields bioactive peptides during digestion or processing. The review identifies four main biological activities:\n\n1. ACE inhibition: chia peptides block angiotensin-converting enzyme, which could lower blood pressure\n2. DPP-4 inhibition: blocking DPP-4 keeps GLP-1 and GIP active longer, improving blood sugar control (the same mechanism as sitagliptin and other diabetes drugs)\n3. Antioxidant activity: scavenging free radicals and reducing oxidative damage\n4. Anti-inflammatory activity: reducing inflammatory markers\n\nChia seeds also contain omega-3 fatty acids, dietary fiber, and gelling agents, making them versatile as functional food ingredients. The bioactive peptides add health-promoting properties beyond basic nutrition.","whyItMatters":"Chia seeds are increasingly popular as health foods. Understanding the specific bioactive peptides they contain and their biological activities adds scientific substance to marketing claims and could guide development of chia-based nutraceutical products.","specificNumbers":"ACE inhibition, DPP-4 inhibition, antioxidant, anti-inflammatory activities; omega-3, fiber, and gelling properties","methodology":"Narrative review of published research on chia seed protein hydrolysis, peptide identification, and biological activity testing. Covers derivation methods, processing effects, and clinical potential.","limitations":"This is a review without new data. Most evidence for chia peptide bioactivities comes from in vitro studies. Human clinical trials demonstrating actual blood pressure or blood sugar effects from chia peptide consumption are lacking. Bioavailability of these peptides after oral ingestion is uncertain."},{"rthcId":"RPEP-05703","title":"Hepcidin Increases Cytokines in Alzheimer's Disease and Down's Syndrome Dementia: Implication of Impaired Iron Homeostasis in Neuroinflammation.","authors":"Raha, Animesh Alexander; Ghaffari, Seyedeh Deniz; Henderson, James; Chakraborty, Subhojit; Allinson, Kieren; Friedland, Robert P; Holland, Anthony; Zaman, Shahid H; Mukaetova-Ladinska, Elizabeta B; Raha-Chowdhury, Ruma","year":2021,"journal":"Frontiers in aging neuroscience, 13, 653591","doi":"10.3389/fnagi.2021.653591","pmid":"33994996","tags":["antimicrobial-peptides","neuroprotection","inflammation","immune-function"],"studyType":"observational","evidenceStrength":"preliminary","keyFinding":"Serum hepcidin levels were significantly increased in Down syndrome subjects compared to controls and Alzheimer's patients. Hepcidin is a member of the defensin family of antimicrobial peptides with dual roles: iron regulation and innate immunity.\n\nIn post-mortem brain sections, hepcidin was found primarily inside macrophages. The researchers propose that most brain hepcidin enters via a compromised blood-brain barrier (BBB), which is known to be disrupted in both AD and DS.\n\nFerritin (iron storage protein) and IL-6 (inflammatory marker) were also measured. The iron metabolism-inflammation connection suggests that disordered iron handling amplifies neuroinflammation in both conditions.\n\nIron dysregulation, hypoxia, and immune complications are all significant concerns in AD and DS, and hepcidin sits at the intersection of all three.","whyItMatters":"Hepcidin connects iron metabolism, innate immunity, and neuroinflammation. Its elevation in Down syndrome dementia and its presence in Alzheimer's brain tissue suggests it may be both a biomarker and a contributor to neurodegeneration. This opens new therapeutic avenues targeting iron-inflammation crosstalk.","specificNumbers":"Hepcidin significantly elevated in DS serum; found in brain macrophages; IL-6 and ferritin also measured","methodology":"Serum samples from AD, DS, and age-matched control subjects were analyzed by ELISA for hepcidin, ferritin, and IL-6. Post-mortem brain sections were assessed by immunohistochemistry for iron-related and inflammatory proteins.","limitations":"The study used cross-sectional serum samples and post-mortem brain tissue, which cannot establish causation. Sample sizes were not specified in the abstract. The mechanism by which hepcidin enters the brain (through compromised BBB) is proposed but not definitively proven. The relationship between peripheral and brain hepcidin levels is complex."},{"rthcId":"RPEP-05704","title":"Inhibition of breast cancer xenografts in a mouse model and the induction of apoptosis in multiple breast cancer cell lines by lactoferricin B peptide.","authors":"Rahman, Rizdwan; Fonseka, Alyssa Danielle; Sua, Shiang-Chia; Ahmad, Munirah; Rajendran, Ramkumar; Ambu, Stephen; Davamani, Fabian; Khoo, Alan Soo-Beng; Chitra, Ebenezer","year":2021,"journal":"Journal of cellular and molecular medicine, 25(15), 7181-7189","doi":"10.1111/jcmm.16748","pmid":"34236134","tags":["bioactive-food-peptides","antimicrobial-peptides","cancer"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"LfcinB was tested against breast cancer cell lines of different subtypes:\n- SKBR3 (HER2+): most sensitive\n- MDA-MB-231 (triple-negative): second most sensitive\n- MDA-MB-468 (triple-negative, EGFR+): moderate sensitivity\n- MCF7 (hormone receptor+): least sensitive\n- MCF-10A (normal breast cells): NOT sensitive to LfcinB\n\nThe selectivity is notable: LfcinB killed cancer cells of varying molecular types while sparing normal breast epithelial cells.\n\nLfcinB also inhibited the invasion of MDA-MB-231 and MDA-MB-468 cells, suggesting it blocks cancer spread as well as growth.\n\nIn the mouse xenograft model, intratumoral LfcinB injections significantly reduced tumor growth rate and final tumor volume and weight, confirmed by IVIS live imaging.","whyItMatters":"Breast cancer is heterogeneous, and finding a single agent that works across multiple subtypes is challenging. LfcinB killed cells from HER2+, triple-negative, and hormone receptor+ subtypes while sparing normal cells. The in vivo confirmation adds weight beyond cell culture data.","specificNumbers":"Sensitivity: SKBR3>MDA-MB-231>MDA-MB-468>MCF7; MCF-10A not affected; tumor volume and weight significantly reduced in mice","methodology":"In vitro: LfcinB tested on 4 breast cancer cell lines and 1 normal breast line for apoptosis induction and invasion inhibition. In vivo: NOD-SCID mice with breast cancer xenografts received intratumoral LfcinB injections. Tumor growth monitored by IVIS live imaging. Harvested tumor volume and weight measured.","limitations":"Intratumoral injection is not a practical delivery route for most clinical scenarios. Systemic delivery (IV or oral) of LfcinB would need to be tested. The peptide's stability in blood and pharmacokinetics were not assessed. The mouse model used immunodeficient animals, so immune contributions were absent."},{"rthcId":"RPEP-05705","title":"Antibiofilm activity of lactoferrin-derived synthetic peptides against Pseudomonas aeruginosa PAO1.","authors":"Ramamourthy, Gopal; Vogel, Hans J","year":2021,"journal":"Biochemistry and cell biology = Biochimie et biologie cellulaire, 99(1), 138-148","doi":"10.1139/bcb-2020-0253","pmid":"32871093","tags":["antimicrobial-peptides","bioactive-food-peptides","infection","peptide-design"],"studyType":"basic-research","evidenceStrength":"preliminary","keyFinding":"Three types of lactoferrin-derived peptides were tested against P. aeruginosa PAO1 biofilms:\n\n1. Short bLfcin(20-25) hexapeptide RRWQWR-NH2: no activity\n2. Human lactoferricin(1-11) GRRRRSVQWCA and bovine lactoferrampin(268-284): almost no activity\n3. Dimeric versions combining two lactoferricin fragments: highly effective\n\nThe dimeric peptides prevented biofilm formation at low concentrations. Some could even eradicate established biofilms, which is much harder than prevention.\n\nFull-length bovine lactoferricin B(17-41) also showed considerable antimicrobial activity.\n\nThe dimeric peptides worked through different mechanisms: some killed bacteria directly (bactericidal), while others appeared to interfere with cell signaling processes that bacteria use to coordinate biofilm formation (likely quorum sensing interference).","whyItMatters":"P. aeruginosa biofilms are a major clinical problem in wound infections, cystic fibrosis lungs, and on medical devices. They resist antibiotics at concentrations 100-1000x higher than needed for free-floating bacteria. Finding peptides that can break up these biofilms addresses a critical unmet need.","specificNumbers":"Monomers: no/minimal activity; dimers: effective prevention, some eradication; bLfcinB(17-41): considerable activity; 2 mechanisms: bactericidal and signaling","methodology":"Peptides were tested using the standard crystal violet biofilm assay and the Calgary biofilm device (which models device-associated biofilms). Both biofilm prevention (treating before biofilm forms) and biofilm eradication (treating established biofilms) were assessed against P. aeruginosa PAO1.","limitations":"Only one bacterial strain (P. aeruginosa PAO1) was tested. Lab-grown biofilms may differ from clinical biofilms. The study did not test toxicity to human cells. Pharmacokinetics and stability of the dimeric peptides were not assessed. The signaling interference mechanism was proposed but not fully characterized."},{"rthcId":"RPEP-05706","title":"Immunoregulatory T cell epitope peptides for the treatment of allergic disease.","authors":"Ramchandani, Rashi; Hossenbaccus, Lubnaa; Ellis, Anne K","year":2021,"journal":"Immunotherapy, 13(15), 1283-1291","doi":"10.2217/imt-2021-0133","pmid":"34558985","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05707","title":"Immunomodulatory Agents Combat Multidrug-Resistant Tuberculosis by Improving Antimicrobial Immunity.","authors":"Rao Muvva, Jagadeeswara; Ahmed, Sultan; Rekha, Rokeya Sultana; Kalsum, Sadaf; Groenheit, Ramona; Schön, Thomas; Agerberth, Birgitta; Bergman, Peter; Brighenti, Susanna","year":2021,"journal":"The Journal of infectious diseases, 224(2), 332-344","doi":"10.1093/infdis/jiab100","pmid":"33606878","tags":["antimicrobial-peptides","immune-function","drug-delivery-systems"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Vitamin D3 plus phenylbutyrate boosted LL-37 antimicrobial peptide production and autophagy in human macrophages, matching the effect of a 125-fold higher dose of isoniazid alone against MDR tuberculosis.","whyItMatters":"Drug-resistant TB kills hundreds of thousands of people each year. If immune-boosting agents like vitamin D and phenylbutyrate can strengthen standard drugs, it could improve outcomes for patients who currently have few treatment options.","specificNumbers":"15 MDR TB strains; 125-fold dose reduction with combo; LL-37 silencing reversed protective effect","methodology":"Lab study using human macrophages infected with 15 clinical TB isolates of varying drug resistance. Measured bacterial growth, gene expression, and protein levels using colony counts, RNA analysis, Western blot, and confocal microscopy.","limitations":"This was a lab study using isolated human immune cells, not a clinical trial. Results in living patients could differ due to drug absorption, immune system complexity, and individual variation."},{"rthcId":"RPEP-05708","title":"The effect of an orally-dosed Caralluma Fimbriata extract on appetite control and body composition in overweight adults.","authors":"Rao, Amanda; Briskey, David; Dos Reis, Carla; Mallard, Alistair R","year":2021,"journal":"Scientific reports, 11(1), 6791","doi":"10.1038/s41598-021-86108-2","pmid":"33762661","tags":["glp-1-receptor-agonists","weight-management","appetite-regulation"],"studyType":"randomized-controlled-trial","evidenceStrength":"moderate","keyFinding":"Caralluma fimbriata extract reduced daily calorie intake by 245 calories, decreased waist circumference by 2.7 cm, and prevented weight gain over 16 weeks in overweight adults.","whyItMatters":"Finding natural compounds that reduce appetite without strict dieting could help many people manage their weight. This extract affected satiety hormones, suggesting a biological mechanism rather than just a placebo effect.","specificNumbers":"83 participants; 16 weeks; 245 cal/day reduction; 2.7 cm waist decrease; leptin stable in CFE vs increased in placebo (p=0.04)","methodology":"Double-blind, randomized, placebo-controlled trial. 83 overweight adults (BMI ~30) took CFE or placebo for 16 weeks. Measured satiety hormones, body composition, and diet at baseline and weeks 4, 8, 12, and 16.","limitations":"Small sample size of 83 people. Mostly female participants (87-93%). No calorie control, so dietary differences could have influenced results. The exact mechanism of action is still unclear."},{"rthcId":"RPEP-05709","title":"Atrial Natriuretic Peptide: Structure, Function, and Physiological Effects: A Narrative Review.","authors":"Rao, Sanjana; Pena, Camilo; Shurmur, Scott; Nugent, Kenneth","year":2021,"journal":"Current cardiology reviews, 17(6), e051121191003","doi":"10.2174/1573403X17666210202102210","pmid":"33530911","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05710","title":"Stable Gastric Pentadecapeptide BPC 157 Heals Established Vesicovaginal Fistula and Counteracts Stone Formation in Rats.","authors":"Rasic, Domagoj; Zenko Sever, Anita; Rasic, Fran; Strbe, Sanja; Rasic, Zarko; Djuzel, Antonija; Duplancic, Bozidar; Boban Blagaic, Alenka; Skrtic, Anita; Seiwerth, Sven; Sikiric, Predrag; Sever, Marko","year":2021,"journal":"Biomedicines, 9(9)","doi":"10.3390/biomedicines9091206","pmid":"34572392","tags":["bpc-157","wound-healing","tissue-repair"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"BPC 157 therapy initiated 2 weeks after fistula creation (when healing had failed) reversed the course within 1 week across all regimens (10 µg/kg and 10 ng/kg, IP or oral). All treated rats showed: cessation of urinary leakage through vagina, increased epithelization, collagenization, granulation tissue and neovascularization, decreased inflammation and necrosis. By study end (day 56), treated rats exhibited 5x larger bladder volume capacity before leaking compared to healthy controls, complete vesical and vaginal defect closure, and zero stone formation — versus persistent fistulas and stone formation in untreated controls.","whyItMatters":"Vesicovaginal fistulas affect millions of women worldwide, particularly in developing countries where surgical repair access is limited. A non-surgical treatment that could heal established fistulas — even when started after healing has failed — would be transformative. BPC 157's effectiveness at nanogram doses and via oral administration makes it potentially practical for resource-limited settings.","specificNumbers":"Treatment delay: 2 weeks; healing within 1 week; 5x bladder capacity; effective at 10 µg/kg and 10 ng/kg; zero stones in treated rats","methodology":"Rats received surgically created vesicovaginal fistulas (4 mm bilateral defects). After 2 weeks confirming failed healing, BPC 157 therapy began at two doses (10 µg/kg and 10 ng/kg) via daily intraperitoneal injection or oral administration in drinking water. Healing was assessed at 1, 2, 4, and 6 weeks post-treatment initiation through macroscopic examination, histological analysis (epithelization, collagenization, granulation, neovascularization, inflammation, necrosis), functional testing (volume capacity), and stone formation assessment.","limitations":"This is an animal study in rats, whose anatomy and fistula healing biology differ significantly from humans. The study was not blinded, introducing potential assessment bias. The fistulas were surgically created under controlled conditions, unlike the complex etiology of human vesicovaginal fistulas (usually from prolonged labor or surgery). No human trials exist for BPC 157 in any fistula indication. The research comes from a single laboratory group that has published extensively on BPC 157."},{"rthcId":"RPEP-05711","title":"Self-assembling peptide hydrogels for the stabilization and sustained release of active Chondroitinase ABC in vitro and in spinal cord injuries.","authors":"Raspa, Andrea; Carminati, Luisa; Pugliese, Raffaele; Fontana, Federico; Gelain, Fabrizio","year":2021,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 330, 1208-1219","doi":"10.1016/j.jconrel.2020.11.027","pmid":"33229053","tags":["drug-delivery-systems","peptide-scaffolds","neuroprotection"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Self-assembling peptide hydrogels extended Chondroitinase ABC activity from less than 72 hours to 42 days in vitro, and improved neural regeneration and behavioral recovery in rats with chronic spinal cord injuries.","whyItMatters":"Spinal cord injuries have very limited treatment options. Chondroitinase ABC shows promise but degrades too quickly. If peptide gels can keep it working for weeks instead of hours, it opens the door to practical therapies for chronic spinal cord damage.","specificNumbers":"42-day enzyme activity vs <72 hours normally; sustained release over 42 days; behavioral recovery observed in chronic SCI rats","methodology":"Lab and animal study. Two types of self-assembling peptide hydrogels were tested with different drug-loading methods. Enzyme activity and release were measured in vitro for 42 days. Hydrogels were injected into rats with chronic spinal cord injuries to assess neural regeneration and movement recovery.","limitations":"Animal study with a small number of rats. Long-term outcomes were not reported. The gel was tested in a specific type of spinal cord injury model, and results may differ in other injury types or in humans."},{"rthcId":"RPEP-05712","title":"Self-assembling tetrameric peptides allow in situ 3D bioprinting under physiological conditions.","authors":"Rauf, Sakandar; Susapto, Hepi H; Kahin, Kowther; Alshehri, Salwa; Abdelrahman, Sherin; Lam, Jordy Homing; Asad, Sultan; Jadhav, Sandip; Sundaramurthi, Dhakshinamoorthy; Gao, Xin; Hauser, Charlotte A E","year":2021,"journal":"Journal of materials chemistry. B, 9(4), 1069-1081","doi":"10.1039/d0tb02424d","pmid":"33406193","tags":["peptide-scaffolds","drug-delivery-systems","bioavailability"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Ultra-short self-assembling peptides enabled in situ 3D bioprinting under physiological conditions, avoiding UV treatment, chemical crosslinking, and viscous bioink methods that damage cells.","whyItMatters":"Keeping cells alive and healthy during 3D printing is one of the biggest challenges in tissue engineering. A bioink that gels gently under normal body conditions could make bioprinting more practical for creating tissues and organs.","specificNumbers":"Tetrameric peptides; printing under physiological conditions; nanomaterials incorporated into scaffolds","methodology":"Lab study developing and testing a new bioprinting method using tetrameric self-assembling peptides. Demonstrated cell printing under physiological conditions and incorporation of nanomaterials into printed scaffolds.","limitations":"Early-stage lab demonstration. No data on long-term cell survival in printed structures. Mechanical properties of the printed scaffolds were not compared to natural tissues. No animal or human testing reported."},{"rthcId":"RPEP-05713","title":"Efficacy and Cardiovascular Safety of Thiazolidinediones.","authors":"Raveendran, Arkiath Veettil; Fernandez, Cornelius James; Jacob, Koshy","year":2021,"journal":"Current drug safety, 16(2), 233-249","doi":"10.2174/1574886315666201026125530","pmid":"33106148","tags":["glp-1-receptor-agonists","insulin-regulation","cardiovascular-effects"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Thiazolidinediones preserve beta cell function and provide durable blood sugar control, but their cardiovascular safety profile is less established than GLP-1 receptor agonists and SGLT2 inhibitors.","whyItMatters":"Choosing diabetes drugs now involves weighing heart safety alongside blood sugar control. Understanding where TZDs stand relative to newer peptide-based drugs helps doctors make better treatment decisions.","specificNumbers":"3 TZD drugs; GLP-1 RAs and SGLT2i have proven CV safety in outcome trials; TZDs preserve beta cell function","methodology":"Narrative review of published literature on thiazolidinedione efficacy, beta cell preservation, and cardiovascular safety, with comparison to GLP-1 receptor agonists and SGLT2 inhibitors.","limitations":"Narrative review, not a systematic review or meta-analysis. May not cover all relevant studies. Comparison between drug classes is indirect since they were not tested head-to-head."},{"rthcId":"RPEP-05714","title":"Effects of growth hormone-releasing hormone receptor antagonist MIA-602 in mice with emotional disorders: a potential treatment for PTSD.","authors":"Recinella, Lucia; Chiavaroli, Annalisa; Orlando, Giustino; Ferrante, Claudio; Veschi, Serena; Cama, Alessandro; Marconi, Guya Diletta; Diomede, Francesca; Gesmundo, Iacopo; Granata, Riccarda; Cai, Renzhi; Sha, Wei; Schally, Andrew V; Brunetti, Luigi; Leone, Sheila","year":2021,"journal":"Molecular psychiatry, 26(12), 7465-7474","doi":"10.1038/s41380-021-01228-5","pmid":"34331008","tags":["growth-hormone-secretagogues","neuroprotection","mental-health"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"GHRH antagonist MIA-602 produced anxiolytic and antidepressant effects in mice after 4 weeks of subcutaneous treatment, mediated through Nrf2 and BDNF signaling in the hippocampus and prefrontal cortex.","whyItMatters":"Current antidepressants and anti-anxiety drugs do not work for everyone and can have significant side effects. GHRH antagonists represent a completely different approach that targets inflammation and oxidative stress rather than serotonin or other traditional pathways.","specificNumbers":"4 weeks subcutaneous treatment; increased Nrf2 and BDNF in hippocampus and prefrontal cortex; anti-inflammatory and antioxidant effects confirmed","methodology":"Animal study in adult mice. MIA-602 was given subcutaneously for 4 weeks. Tested anxiety and depression-like behaviors using standard behavioral tests. Measured inflammatory markers, oxidative stress, Nrf2, and BDNF in brain tissue.","limitations":"Animal study only. Mouse models of anxiety and depression do not fully replicate human mood disorders. No comparison to existing antidepressant or anti-anxiety drugs. Long-term effects and safety are unknown."},{"rthcId":"RPEP-05715","title":"Growth hormone-releasing hormone antagonistic analog MIA-690 stimulates food intake in mice.","authors":"Recinella, Lucia; Chiavaroli, Annalisa; Orlando, Giustino; Ferrante, Claudio; Gesmundo, Iacopo; Granata, Riccarda; Cai, Renzhi; Sha, Wei; Schally, Andrew V; Brunetti, Luigi; Leone, Sheila","year":2021,"journal":"Peptides, 142, 170582","doi":"10.1016/j.peptides.2021.170582","pmid":"34051291","tags":["growth-hormone-secretagogues","appetite-regulation","weight-management"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"GHRH antagonist MIA-690 increased food intake and body weight in mice by elevating hypothalamic AgRP and norepinephrine while reducing serotonin and visceral fat leptin expression.","whyItMatters":"Understanding how GHRH analogs affect appetite could help develop treatments for conditions involving weight loss, such as cancer cachexia or age-related wasting. It also reveals unexpected metabolic effects of these peptides.","specificNumbers":"MIA-690 increased food intake and body weight; elevated AgRP and norepinephrine; reduced serotonin and leptin; MR-409 had no effect on any measure","methodology":"Animal study. Mice received chronic subcutaneous injections of MIA-690, MR-409, or vehicle. Measured food intake, body weight, locomotor activity, fat mass, and hypothalamic gene expression and neurotransmitter levels.","limitations":"Animal study in mice. Effects may not translate to humans. Only chronic dosing was tested. No dose-response data provided. The exact mechanism linking GHRH antagonism to appetite stimulation is not fully explained."},{"rthcId":"RPEP-05716","title":"Protective effects of growth hormone-releasing hormone analogs in DSS-induced colitis in mice.","authors":"Recinella, Lucia; Chiavaroli, Annalisa; Di Valerio, Valentina; Veschi, Serena; Orlando, Giustino; Ferrante, Claudio; Gesmundo, Iacopo; Granata, Riccarda; Cai, Renzhi; Sha, Wei; Schally, Andrew V; Lattanzio, Rossano; Brunetti, Luigi; Leone, Sheila","year":2021,"journal":"Scientific reports, 11(1), 2530","doi":"10.1038/s41598-021-81778-4","pmid":"33510215","tags":["growth-hormone-secretagogues","gut-health","inflammation"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Both GHRH analogs — the antagonist MIA-690 and the agonist MR-409 — attenuated DSS-induced colitis in mice, improving clinical symptoms and reducing histopathological damage.\n\nIn ex vivo colon tissue, both peptides inhibited production of pro-inflammatory and oxidative markers triggered by bacterial toxin (LPS). In live mice, both reduced pain responses in hot plate and formalin tests and decreased sensitivity to inflammatory stimuli.\n\nMIA-690 showed superior efficacy compared to MR-409, more strongly inhibiting prostaglandin E2, 8-iso-PGF2α, serotonin, TNF-α, IL-6, and nitric oxide synthase gene expression in colitis-affected colon tissue. MIA-690 also uniquely decreased serum IGF-1 levels in colitis mice, which may explain its stronger anti-inflammatory and antioxidant activity.","whyItMatters":"Current treatments for inflammatory bowel disease often have significant side effects and don't work for all patients. GHRH analogs represent a completely different therapeutic approach — targeting hormonal pathways rather than the immune system directly. The finding that both an agonist and antagonist of the same hormone receptor can reduce gut inflammation suggests a complex regulatory mechanism that could open new treatment avenues.","specificNumbers":"MIA-690 reduced PGE2, 8-iso-PGF2α, 5-HT, TNF-α, IL-6, iNOS, and serum IGF-1; both analogs reduced pain and clinical symptoms; MIA-690 showed higher efficacy than MR-409","methodology":"Researchers used both ex vivo and in vivo approaches. Isolated mouse colon specimens were exposed to bacterial lipopolysaccharide (LPS) to trigger inflammation, then treated with MIA-690 or MR-409. In live male mice, colitis was induced using dextran sodium sulfate (DSS) in drinking water. Peptides were administered subcutaneously. Pain sensitivity was assessed using hot plate and formalin tests. The team measured clinical colitis symptoms, histopathological tissue damage, inflammatory markers (PGE2, TNF-α, IL-6, iNOS), oxidative stress markers (8-iso-PGF2α), serotonin levels, and serum IGF-1.","limitations":"This is an animal study using a chemical model of colitis (DSS), which does not fully replicate the complexity of human inflammatory bowel disease. The study was short-term, so long-term effects and safety are unknown. Specific dosages and group sizes are not reported in the abstract. There was no comparison to standard colitis treatments like aminosalicylates or biologics, making it hard to judge relative effectiveness."},{"rthcId":"RPEP-05717","title":"New generation of cell-penetrating peptides: Functionality and potential clinical application.","authors":"Reissmann, Siegmund; Filatova, Margarita P","year":2021,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 27(5), e3300","doi":"10.1002/psc.3300","pmid":"33615648","tags":["drug-delivery-systems","antimicrobial-peptides","cancer-research"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"New-generation CPPs address three major limitations of earlier peptides:\n\n1. **Cell selectivity**: Hybrid designs combine homing sequences for tissue targeting with activation sequences that only work at the target site, dramatically improving specificity.\n\n2. **Protease stability**: Conjugation to nanoparticles and structural modifications protect CPPs from enzymatic degradation in the body.\n\n3. **Endosomal escape**: Engineered sequences enable CPPs to break out of endosomes (cellular compartments that trap delivered cargo), ensuring drugs actually reach their intracellular targets.\n\nSeveral naturally tumor-selective CPPs were highlighted — azurin, crotamine, maurocalcine, lycosin-I, buffalo cathelicidin, and peptide CB5005 — which can both penetrate cancer cell membranes and directly exert cytotoxic effects through intracellular signaling pathways.\n\nNotably, certain CPPs can now penetrate the blood-brain barrier, skin, and eye tissues, enabling non-invasive delivery via sprays, creams, and drops instead of injections.","whyItMatters":"Getting drugs to the right cells inside the body remains one of medicine's biggest challenges. Most large therapeutic molecules (proteins, nucleic acids, antibodies) cannot cross cell membranes on their own. CPPs that can selectively deliver these cargoes to tumor cells, across the blood-brain barrier, or through skin could transform treatment for cancer, neurological diseases, and eye conditions — while making treatment less invasive and more patient-friendly.","specificNumbers":"CPPs covered: azurin, crotamine, maurocalcine, lycosin-I, cathelicidin, CB5005; barriers: skin, BBB, eye; delivery: nanoparticle conjugation, sprays, creams, drops","methodology":"This is a narrative review of recent literature on next-generation cell-penetrating peptides. It covers CPPs derived from natural sources (venoms, bacterial proteins, cathelicidins) as well as rationally designed hybrid structures. The review discusses mechanisms of cell entry, nanoparticle conjugation strategies, barrier-crossing capabilities, and 3D tissue penetration for tumor treatment.","limitations":"This is a review article that does not generate new experimental data. Most CPPs discussed remain in preclinical development. Comparing CPP efficacy is inherently difficult because performance depends on the specific cargo, target tissue, coupling method, and experimental conditions. Clinical translation faces challenges including manufacturing scalability, immunogenicity, and regulatory approval of novel delivery systems."},{"rthcId":"RPEP-05718","title":"New insights into the digestion and bioavailability of a high-melting-temperature solid triacylglycerol fraction in bovine milk fat.","authors":"Ren, Qingxi; Fu, Ling; Dudu, Olayemi E; Zhang, Rui; Liu, Haiyan; Zheng, Zhiqiang; Ma, Ying","year":2021,"journal":"Food & function, 12(12), 5274-5286","doi":"10.1039/d1fo00259g","pmid":"34008635","tags":["glp-1-receptor-agonists","appetite-regulation","weight-management"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"High-melting solid milk fat fraction increased GLP-1, CCK, and PYY satiety peptide levels in rats, induced weight loss, reduced fat accumulation, and upregulated hepatic lipolysis enzymes without causing dyslipidemia.","whyItMatters":"This shows that specific fat fractions in milk can trigger satiety peptides like GLP-1 and PYY. Understanding which food components activate these pathways could inform dietary strategies for weight management.","specificNumbers":"GLP-1, CCK, PYY increased; 4-week diet; HSL, ATGL, PKA upregulated; ACC downregulated; no dyslipidemia; improved adipocyte hypertrophy","methodology":"Animal study in rats. Short-term (240 min post-gavage) and long-term (4 weeks dietary) experiments compared solid milk fat fraction to whole butterfat. Measured satiety hormones, blood lipids, liver enzymes, adipocyte size, and gene expression.","limitations":"Animal study in rats. Milk fat fractions used were experimentally prepared and may not match commercial dairy products. Short study duration of 4 weeks. Human responses to these fat fractions may differ."},{"rthcId":"RPEP-05719","title":"Peptide Dendrimers: From Enzyme Models to Antimicrobials and Transfection Reagents.","authors":"Reymond, Jean-Louis","year":2021,"journal":"Chimia, 75(6), 535-538","doi":"10.2533/chimia.2021.535","pmid":"34233820","tags":["antimicrobial-peptides","drug-delivery-systems","peptide-engineering"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Peptide dendrimers serve as versatile platforms for antimicrobials against multidrug-resistant Gram-negative bacteria and as transfection reagents for siRNA and CRISPR-Cas9 delivery.","whyItMatters":"Drug-resistant bacteria are a major global threat, and delivering gene therapies like CRISPR remains challenging. Peptide dendrimers address both problems with a single versatile platform that can be rapidly screened and optimized.","specificNumbers":"Applications: enzyme models, biofilm inhibitors, antimicrobials vs MDR Gram-negative bacteria, siRNA/CRISPR transfection; AI and stereorandomization now used for design","methodology":"Review of research using combinatorial library synthesis and screening to develop peptide dendrimers for multiple applications. Includes enzyme modeling, lectin binding, antimicrobial testing, and gene delivery experiments.","limitations":"Review article covering many applications broadly. Most applications are in early research stages. Scalability and cost of dendrimer synthesis for clinical use are not addressed."},{"rthcId":"RPEP-05720","title":"MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis.","authors":"Reynolds, Joseph C; Lai, Rochelle W; Woodhead, Jonathan S T; Joly, James H; Mitchell, Cameron J; Cameron-Smith, David; Lu, Ryan; Cohen, Pinchas; Graham, Nicholas A; Benayoun, Bérénice A; Merry, Troy L; Lee, Changhan","year":2021,"journal":"Nature communications, 12(1), 470","doi":"10.1038/s41467-020-20790-0","pmid":"33473109","tags":["mots-c","aging","exercise"],"studyType":"Basic Science (Animal + Human)","evidenceStrength":"Strong","keyFinding":"MOTS-c, a peptide encoded by mitochondrial DNA, significantly enhanced physical performance in young (2 months), middle-aged (12 months), and old (22 months) mice. Most remarkably, when MOTS-c treatment was started very late in life (23.5 months — equivalent to roughly 70+ human years) at just 3 times per week, it still increased physical capacity and healthspan.\n\nThe study also showed that exercise naturally increases MOTS-c levels in both skeletal muscle and blood circulation in humans, establishing MOTS-c as an exercise-induced factor. At the molecular level, MOTS-c regulates nuclear genes related to metabolism and protein quality control (proteostasis), directly affects skeletal muscle metabolism, and helps muscle cells (myoblasts) adapt to metabolic stress.","whyItMatters":"This is one of the most important MOTS-c studies published because it demonstrates three critical things: (1) a mitochondrial-encoded peptide can actively regulate the aging process, (2) even late-life treatment can improve physical function, and (3) exercise naturally produces MOTS-c in humans. The finding that intermittent MOTS-c treatment started in very old mice still improved healthspan challenges the assumption that anti-aging interventions must start early to be effective. It also positions MOTS-c as a potential exercise mimetic for people who cannot exercise.","specificNumbers":"Enhanced performance in mice at 2, 12, and 22 months · late-life treatment started at 23.5 months · 3x/week intermittent dosing · exercise induces MOTS-c in human muscle + circulation · regulates nuclear gene expression","methodology":"Multi-component study combining mouse experiments and human exercise data. Mice at three age groups received MOTS-c and were tested for physical performance. A separate cohort started treatment at 23.5 months (late life) with intermittent 3x/week dosing. In humans, skeletal muscle biopsies and blood samples were collected before and after exercise to measure endogenous MOTS-c levels. Molecular analyses included gene expression profiling, metabolomics in skeletal muscle, and myoblast stress response assays.","limitations":"While MOTS-c improved physical capacity in mice, the study does not fully characterize all aspects of healthspan (cognitive function, organ-specific aging, etc.). The human component confirms that exercise induces MOTS-c but does not test exogenous MOTS-c administration in humans. Specific dosing details and the magnitude of physical performance improvements are not detailed in the abstract. Long-term safety of exogenous MOTS-c in any species remains to be established. The mechanisms by which a mitochondrial-encoded peptide regulates nuclear gene expression are still being elucidated."},{"rthcId":"RPEP-05721","title":"The Potential of Human Peptide LL-37 as an Antimicrobial and Anti-Biofilm Agent.","authors":"Ridyard, Kylen E; Overhage, Joerg","year":2021,"journal":"Antibiotics (Basel, Switzerland), 10(6)","doi":"10.3390/antibiotics10060650","pmid":"34072318","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05722","title":"Growth hormone-releasing hormone agonists ameliorate chronic kidney disease-induced heart failure with preserved ejection fraction.","authors":"Rieger, Angela C; Bagno, Luiza L; Salerno, Alessandro; Florea, Victoria; Rodriguez, Jose; Rosado, Marcos; Turner, Darren; Dulce, Raul A; Takeuchi, Lauro M; Kanashiro-Takeuchi, Rosemeire M; Buchwald, Peter; Wanschel, Amarylis C B A; Balkan, Wayne; Schulman, Ivonne H; Schally, Andrew V; Hare, Joshua M","year":2021,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 118(4)","doi":"10.1073/pnas.2019835118","pmid":"33468654","tags":["growth-hormone-secretagogues","cardiovascular-effects","heart-health"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"GHRH agonist MR-409 normalized end-diastolic pressure, improved calcium transients, reduced pro-BNP, and restored titin isoform ratios in pigs with CKD-induced HFpEF after 4-6 weeks of treatment.","whyItMatters":"HFpEF affects millions of people and has no effective drug treatments. This large-animal study shows GHRH agonists could be a breakthrough therapy by directly improving how the heart relaxes and fills with blood.","specificNumbers":"16 pigs; 30 µg/kg daily SC; EDP normalized p=0.03; EDP/EDV p=0.018; Ca²⁺ transient p=0.009; titin ratio p=0.0022; 4-6 weeks treatment","methodology":"Randomized, placebo-controlled animal study. 16 female Yorkshire pigs underwent 5/6 nephrectomy. At 12 weeks, randomized to daily subcutaneous MR-409 (30 µg/kg, n=8) or placebo (n=8) for 4-6 weeks. Assessed cardiac hemodynamics, calcium handling, and molecular markers.","limitations":"Animal study in pigs, not humans. Small sample of 16 animals. The CKD-HFpEF model may not capture all features of human HFpEF. Short treatment duration of 4-6 weeks. Long-term effects unknown."},{"rthcId":"RPEP-05723","title":"Antimicrobial Peptides: A Potent Alternative to Antibiotics.","authors":"Rima, Mariam; Rima, Mohamad; Fajloun, Ziad; Sabatier, Jean-Marc; Bechinger, Burkhard; Naas, Thierry","year":2021,"journal":"Antibiotics (Basel, Switzerland), 10(9)","doi":"10.3390/antibiotics10091095","pmid":"34572678","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05724","title":"Localized Enzyme-Assisted Self-Assembly in the Presence of Hyaluronic Acid for Hybrid Supramolecular Hydrogel Coating.","authors":"Rodon Fores, Jennifer; Bigo-Simon, Alexis; Wagner, Déborah; Payrastre, Mathilde; Damestoy, Camille; Blandin, Lucille; Boulmedais, Fouzia; Kelber, Julien; Schmutz, Marc; Rabineau, Morgane; Criado-Gonzalez, Miryam; Schaaf, Pierre; Jierry, Loïc","year":2021,"journal":"Polymers, 13(11)","doi":"10.3390/polym13111793","pmid":"34072331","tags":["peptide-scaffolds","drug-delivery-systems","bioavailability"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Localized enzyme-assisted self-assembly produced peptide-based supramolecular hydrogel coatings whose properties could be precisely tuned by varying hyaluronic acid concentration. Coating thickness ranged from 18 µm (at 10 mg/mL HA) to 41 µm (at 2 mg/mL HA), while the elastic modulus decreased from 2 kPa to 0.2 kPa as HA concentration increased.\n\nHigher HA concentrations caused peptide nanofibers to collapse into larger microstructures, fundamentally altering the internal architecture of the hydrogel. Despite these structural changes, all formulations supported NIH 3T3 fibroblast viability and adhesion.","whyItMatters":"Medical implants often trigger inflammation because the body recognizes them as foreign. Coating implants with biocompatible hydrogels could reduce this reaction. This study demonstrates a fully biocompatible method to create tunable peptide coatings that incorporate hyaluronic acid — a molecule the body already produces — which could lead to implants that integrate more smoothly with surrounding tissue.","specificNumbers":"Thickness: 18-41 µm; elastic modulus: 0.2-2 kPa; HA: 2, 5, 10 mg/mL; fibroblast viability confirmed","methodology":"Peptide hydrogels were grown on surfaces using localized enzyme-assisted self-assembly with varying concentrations of hyaluronic acid (2, 5, and 10 mg/mL). The coatings were characterized using electron microscopy, fluorescent confocal microscopy, and rheological measurements. Cell viability and adhesion were tested using NIH 3T3 fibroblast cultures.","limitations":"This is an in vitro study only. The coatings have not been tested on actual implants in animal models or humans. Only one cell type (fibroblasts) was evaluated, so performance with other relevant cell types (immune cells, osteoblasts) is unknown. Long-term stability and degradation behavior in physiological conditions were not assessed."},{"rthcId":"RPEP-05725","title":"Effects of growth hormone-releasing hormone agonistic analog MR-409 on insulin-secreting cells under cyclopiazonic acid-induced endoplasmic reticulum stress.","authors":"Rodrigues-Dos-Santos, Karina; Soares, Gabriela M; Guimarães, Dimitrius S P S F; Araújo, Thiago R; Vettorazzi, Jean F; Zangerolamo, Lucas; Marconato-Júnior, Emilio; Cai, Renzhi; Sha, Wei; Schally, Andrew V; Boschero, Antônio C; Barbosa, Helena C L","year":2021,"journal":"Molecular and cellular endocrinology, 535, 111379","doi":"10.1016/j.mce.2021.111379","pmid":"34252492","tags":["growth-hormone-secretagogues","insulin-regulation","oxidative-stress-related"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"GHRH agonist MR-409 did not prevent ER stress in INS-1E cells but reduced oxidative stress and improved cell survival under ER stress conditions induced by cyclopiazonic acid.","whyItMatters":"Beta cell death from ER stress is a key driver of type 2 diabetes progression. Finding that GHRH agonists can keep these cells alive even under stress could lead to treatments that preserve insulin production.","specificNumbers":"Reduced oxidative stress; improved cell survival; ER stress not prevented; INS-1E cell line","methodology":"Lab study using INS-1E insulin-secreting cells. ER stress was induced by cyclopiazonic acid. Cells were treated with MR-409 and assessed for ER stress markers, oxidative stress, and cell survival.","limitations":"Lab study using a single cell line (INS-1E), not primary human beta cells. ER stress was chemically induced, which may not fully represent the gradual stress seen in diabetes. The protective mechanism is not yet fully understood."},{"rthcId":"RPEP-05726","title":"Ketogenic diets and appetite regulation.","authors":"Roekenes, Jessica; Martins, Catia","year":2021,"journal":"Current opinion in clinical nutrition and metabolic care, 24(4), 359-363","doi":"10.1097/MCO.0000000000000760","pmid":"33883420","tags":["appetite-regulation","weight-management","metabolic-health"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Ketogenic diets suppress ghrelin increases and boost satiety peptide release during weight loss, with higher beta-hydroxybutyrate levels correlating with greater appetite suppression.","whyItMatters":"Hunger is the main reason diets fail. If ketogenic diets naturally suppress appetite through hormonal changes, this could explain their effectiveness and help design better weight loss approaches.","specificNumbers":"Ghrelin increase suppressed; satiety peptides increased; higher β-hydroxybutyrate = less hunger; exogenous ketones show similar effects","methodology":"Narrative review of studies published over the previous 2 years on ketogenic diets and appetite regulation, including both dietary ketosis and exogenous ketone studies.","limitations":"Narrative review, not a systematic review or meta-analysis. Many included studies had small sample sizes. The exact mechanisms linking ketones to appetite suppression are still not fully identified."},{"rthcId":"RPEP-05727","title":"Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial.","authors":"Rosenstock, Julio; Wysham, Carol; Frías, Juan P; Kaneko, Shizuka; Lee, Clare J; Fernández Landó, Laura; Mao, Huzhang; Cui, Xuewei; Karanikas, Chrisanthi A; Thieu, Vivian T","year":2021,"journal":"Lancet (London, England), 398(10295), 143-155","doi":"10.1016/S0140-6736(21)01324-6","pmid":"34186022","tags":["glp-1-receptor-agonists","weight-management","insulin-regulation"],"studyType":"randomized-controlled-trial","evidenceStrength":"strong","keyFinding":"Tirzepatide (5, 10, 15 mg weekly) reduced HbA1c by 1.87-2.07% and body weight by 7.0-9.5 kg over 40 weeks vs placebo, with no severe hypoglycemia in 478 patients with type 2 diabetes.","whyItMatters":"Tirzepatide combines two incretin pathways in one drug, achieving better blood sugar and weight outcomes than most single-pathway drugs. This trial helped establish it as a major new option for type 2 diabetes.","specificNumbers":"478 patients; 52 sites in 4 countries; HbA1c: -1.87 to -2.07% vs +0.04% placebo; weight: -7.0 to -9.5 kg; nausea 12-18%; no severe hypoglycemia; 40 weeks","methodology":"Double-blind, randomized, placebo-controlled phase 3 trial (SURPASS-1) at 52 centers in 4 countries. 478 adults with type 2 diabetes randomized 1:1:1:1 to tirzepatide 5, 10, or 15 mg weekly or placebo for 40 weeks.","limitations":"40-week duration may not capture long-term safety. Participants were treatment-naive (no prior injectable therapy), so results may differ in previously treated patients. Funded by Eli Lilly. Gastrointestinal side effects affected a notable proportion of patients."},{"rthcId":"RPEP-05728","title":"Behavioural and neurochemical mechanisms underpinning the feeding-suppressive effect of GLP-1/CCK combinatorial therapy.","authors":"Roth, Emma; Benoit, Simon; Quentin, Baptiste; Lam, Brian; Will, Sarah; Ma, Marcella; Heeley, Nick; Darwish, Tamana; Shrestha, Yashaswi; Gribble, Fiona; Reimann, Frank; Pshenichnaya, Irina; Yeo, Giles; Baker, David J; Trevaskis, James L; Blouet, Clemence","year":2021,"journal":"Molecular metabolism, 43, 101118","doi":"10.1016/j.molmet.2020.101118","pmid":"33221554","tags":["glp-1-receptor-agonists","appetite-regulation","weight-management"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"GLP-1R and CCK1R co-agonism produced enhanced appetite suppression through Calcrl+ neurons in the nucleus of the solitary tract, first reducing meal size then meal number for sustained feeding suppression.","whyItMatters":"Single-target obesity drugs often plateau in effectiveness. Understanding how combining gut hormone signals produces stronger appetite suppression could lead to more powerful combination therapies for obesity.","specificNumbers":"Combination > either alone; initial meal size reduction then meal number reduction; NTS is convergence site; Calcrl+ neurons identified via PhosphoTRAP","methodology":"Animal study in lean and high-fat diet mice. Measured acute and long-term feeding, body weight, and brain neuronal activation using immunohistochemistry. Used PhosphoTRAP to identify specific neuron populations activated by the drug combination.","limitations":"Animal study in mice. Brain circuits in humans may differ. The Calcrl+ neuron population needs further characterization. Only two agonists were combined, while the gut releases many more hunger-regulating peptides."},{"rthcId":"RPEP-05729","title":"Exploiting B-cell Receptor Stereotypy to Design Tailored Immunotherapy in Chronic Lymphocytic Leukemia.","authors":"Rovida, Alessandra; Maccalli, Cristina; Scarfò, Lydia; Dellabona, Paolo; Stamatopoulos, Kostas; Ghia, Paolo","year":2021,"journal":"Clinical cancer research : an official journal of the American Association for Cancer Research, 27(3), 729-739","doi":"10.1158/1078-0432.CCR-20-1632","pmid":"33051305","tags":["cancer-research","immune-function","peptide-engineering"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Peptide vaccines based on stereotyped VH CDR3 sequences from CLL B-cell receptors generated specific T-cell responses, controlled leukemia development, and increased survival in a transplantable mouse model.","whyItMatters":"CLL is common and often incurable. Peptide vaccines that work for groups of patients sharing receptor patterns could provide a practical, scalable immunotherapy without the cost and complexity of personalized approaches.","specificNumbers":"~30% of CLL patients with stereotyped BcR IG; subsets #1 and #2 targeted; vaccination controlled leukemia; increased overall survival in mice","methodology":"Lab and animal study. Identified immunogenic peptides from consensus CLL receptor sequences. Generated T cells in vitro. Tested vaccine in a transplantable CLL mouse model. Assessed T-cell reactivity, leukemia control, and survival.","limitations":"Mouse model only. Vaccination was given before leukemia challenge (preventive, not therapeutic). Human immune responses to these peptides may differ. Only stereotyped CLL subsets (30% of patients) would be eligible."},{"rthcId":"RPEP-05730","title":"Self-Assembling Peptides and Carbon Nanomaterials Join Forces for Innovative Biomedical Applications.","authors":"Rozhin, Petr; Charitidis, Costas; Marchesan, Silvia","year":2021,"journal":"Molecules (Basel, Switzerland), 26(13)","doi":"10.3390/molecules26134084","pmid":"34279424","tags":["peptide-scaffolds","drug-delivery-systems","peptide-engineering"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Self-assembling peptide and carbon nanomaterial hybrids enable applications in tissue regeneration, biosensing, bioimaging, and bioelectronics through creative integration of chemically different building blocks.","whyItMatters":"Neither peptides nor carbon nanomaterials alone can do everything needed for advanced biomedical devices. Combining them creates materials with both biological compatibility and electronic/structural properties needed for next-generation medical tools.","specificNumbers":"Applications: tissue regeneration, biosensing, imaging, bioelectronics; carbon materials: nanotubes, graphene, fullerenes","methodology":"Concise review of recent literature on combining self-assembling peptides with carbon nanostructures (nanotubes, graphene, fullerenes) for biomedical applications.","limitations":"Review article covering a broad field. Most applications discussed are at the proof-of-concept stage. Biocompatibility and long-term safety of carbon nanomaterials in the body are still debated."},{"rthcId":"RPEP-05731","title":"Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial.","authors":"Rubino, Domenica; Abrahamsson, Niclas; Davies, Melanie; Hesse, Dan; Greenway, Frank L; Jensen, Camilla; Lingvay, Ildiko; Mosenzon, Ofri; Rosenstock, Julio; Rubio, Miguel A; Rudofsky, Gottfried; Tadayon, Sayeh; Wadden, Thomas A; Dicker, Dror","year":2021,"journal":"JAMA, 325(14), 1414-1425","doi":"10.1001/jama.2021.3224","pmid":"33755728","tags":[],"studyType":"randomized-controlled-trial","evidenceStrength":"strong","keyFinding":"After an initial 20-week period where all participants lost an average of 10.6% body weight on semaglutide 2.4 mg, those who continued semaglutide lost an additional 7.9% body weight over 48 more weeks, while those switched to placebo regained 6.9%. The net difference was a staggering 14.8 percentage points between continuing and stopping the drug.\n\nBeyond weight, continuing semaglutide also produced significant improvements in waist circumference (-9.7 cm vs placebo), systolic blood pressure (-3.9 mmHg vs placebo), and physical functioning scores. By the end of the full 68-week period, people who stayed on semaglutide had lost a total of approximately 17.4% of their starting body weight.\n\nGastrointestinal side effects occurred in 49.1% of those continuing semaglutide vs 26.1% on placebo, but dropout rates due to adverse events were similar (2.4% vs 2.2%). Study completion was remarkably high at 98%.","whyItMatters":"This is one of the most important studies in the semaglutide weight loss program because it definitively answers the question: what happens when you stop? The answer is clear — weight comes back. This has major implications for how patients and doctors approach GLP-1 therapy, confirming that semaglutide for obesity is likely a long-term or lifelong treatment rather than a short-term intervention. It also demonstrates that continuing treatment produces ongoing benefits beyond just weight loss.","specificNumbers":"n=803 randomized · 10.6% weight loss in run-in · -7.9% continued vs +6.9% placebo (weeks 20-68) · 14.8 percentage point difference · p<0.001 · -9.7 cm waist difference · -3.9 mmHg systolic BP · 98% trial completion · 73 sites, 10 countries","methodology":"This was a randomized, double-blind, phase 3a withdrawal trial (STEP 4) conducted at 73 sites in 10 countries. All 902 participants first received semaglutide 2.4 mg weekly for 20 weeks (16 weeks dose escalation + 4 weeks maintenance). Then 803 participants who reached the maintenance dose were randomized 2:1 to either continue semaglutide (n=535) or switch to placebo (n=268) for 48 more weeks. Both groups received lifestyle intervention throughout. Primary endpoint was percent body weight change from week 20 to week 68.","limitations":"The study excluded people with diabetes, so results may not fully apply to that population. The 20-week run-in means participants who couldn't tolerate semaglutide were already filtered out before randomization. The placebo group's weight regain demonstrates drug dependence for weight maintenance, raising questions about lifelong treatment costs and sustainability."},{"rthcId":"RPEP-05732","title":"Cell-Penetrating Peptides Derived from Animal Venoms and Toxins.","authors":"Rádis-Baptista, Gandhi","year":2021,"journal":"Toxins, 13(2)","doi":"10.3390/toxins13020147","pmid":"33671927","tags":["cell-penetrating","venom-peptides","peptide-delivery","peptide-design"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"The review covers venom-derived CPPs from multiple animal groups:\n\n- Insects: melittin, anoplin, mastoparans (from bees and wasps)\n- Arachnids: latarcin, lycosin, chlorotoxin, maurocalcine/imperatoxin homologs, wasabi receptor toxin (from spiders and scorpions)\n- Fish: pardaxins\n- Amphibians: bombesin\n- Snakes: crotamine and cathelicidins\n\nThese peptides share common features: they are cysteine-stabilized or linear alpha-helical, cationic (positively charged), and amphipathic (having both water-loving and fat-loving regions).\n\nVenom CPPs can be modified to enhance cell selectivity, reduce toxicity, and carry diverse cargo including drugs, nucleic acids, nanoparticles, metals, and radionuclides. They can be attached to cargo via N- or C-terminal conjugation or through complex formation.","whyItMatters":"Nature has evolved thousands of peptides that can cross cell membranes. Venoms are a particularly rich source because venom components must penetrate target cells to exert their effects. Cataloging and characterizing these peptides provides a toolbox for drug delivery.","specificNumbers":"Sources: insects, arachnids, snakes, fish, amphibians; peptides: melittin, mastoparans, chlorotoxin, crotamine, pardaxin, bombesin; cargo: drugs, nucleic acids, NPs","methodology":"Comprehensive narrative review of published literature on cell-penetrating peptides from animal venoms and toxic secretions, covering their discovery, structural properties, modifications, and applications.","limitations":"This is a review without new experimental data. Many venom CPPs have only been tested in cell culture. Toxicity remains a challenge for most venom-derived peptides. The modifications needed to make them safe may alter their cell-penetrating properties. In vivo data are limited for most peptides listed."},{"rthcId":"RPEP-05733","title":"Suprastapled Peptides: Hybridization-Enhanced Peptide Ligation and Enforced α-Helical Conformation for Affinity Selection of Combinatorial Libraries.","authors":"Sabale, Pramod M; Imiołek, Mateusz; Raia, Pierre; Barluenga, Sofia; Winssinger, Nicolas","year":2021,"journal":"Journal of the American Chemical Society, 143(45), 18932-18940","doi":"10.1021/jacs.1c07013","pmid":"34739233","tags":["peptide-engineering","cancer-research","drug-delivery-systems"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"PNA-peptide hybridization enabled one-pot combinatorial ligation and helical stabilization of 100 peptides, with affinity selection identifying potent binders of the p53/MDM2 interaction.","whyItMatters":"Protein-protein interactions are involved in many diseases but are hard to drug. This method makes it much faster and easier to find stapled peptides that block these interactions, which could speed up drug discovery.","specificNumbers":"100 peptides in one-pot reaction; PNA-peptide hybridization; affinity selection against MDM2; mass spectrometry identification","methodology":"Lab study using native chemical ligation of PNA-peptide conjugates. 100 peptides generated in one reaction, screened by affinity selection against MDM2 on beads, and best binders identified by mass spectrometry.","limitations":"Proof-of-concept study using one target (MDM2). The method needs validation against other protein-protein interactions. Binding affinity does not guarantee cell activity or drug-like properties."},{"rthcId":"RPEP-05734","title":"Randomized phase II trial of lymphodepletion plus adoptive cell transfer of tumor-infiltrating lymphocytes, with or without dendritic cell vaccination, in patients with metastatic melanoma.","authors":"Saberian, Chantal; Amaria, Rodabe N; Najjar, Amer M; Radvanyi, Laszlo G; Haymaker, Cara L; Forget, Marie-Andrée; Bassett, Roland L; Faria, Silvana C; Glitza, Isabella C; Alvarez, Enrique; Parshottam, Sapna; Prieto, Victor; Lizée, Gregory; Wong, Michael K; McQuade, Jennifer L; Diab, Adi; Yee, Cassian; Tawbi, Hussein A; Patel, Sapna; Shpall, Elizabeth J; Davies, Michael A; Hwu, Patrick; Bernatchez, Chantale","year":2021,"journal":"Journal for immunotherapy of cancer, 9(5)","doi":"10.1136/jitc-2021-002449","pmid":"34021033","tags":["cancer-research","immune-function","peptide-engineering"],"studyType":"randomized-controlled-trial","evidenceStrength":"moderate","keyFinding":"MART-1 peptide-pulsed dendritic cell vaccination did not improve persistence of tumor-specific T cells when added to TIL therapy in metastatic melanoma. Response rates were 30% (TIL) vs 50% (TIL+DC) but the study was underpowered.","whyItMatters":"Combination immunotherapies are the future of cancer treatment. Understanding which combinations actually improve outcomes helps focus research on the most promising approaches.","specificNumbers":"18 patients; 10 TIL alone, 8 TIL+DC; response 30% vs 50%; no difference in MART-1 T cell persistence; well tolerated","methodology":"Phase II randomized clinical trial. 18 patients with stage IV melanoma randomized to TIL alone (n=10) or TIL plus MART-1 peptide-pulsed dendritic cells (n=8). Tracked MART-1 specific CD8+ T cells by flow cytometry. Measured objective response rates.","limitations":"Very small trial with only 18 patients. Not powered to detect differences in response rates. Single melanoma antigen (MART-1) targeted. Results may not apply to other antigens or cancer types."},{"rthcId":"RPEP-05735","title":"A Molecular Lid Mechanism of K+ Channel Blocker Action Revealed by a Cone Peptide.","authors":"Saikia, Chandamita; Dym, Orly; Altman-Gueta, Hagit; Gordon, Dalia; Reuveny, Eitan; Karbat, Izhar","year":2021,"journal":"Journal of molecular biology, 433(17), 166957","doi":"10.1016/j.jmb.2021.166957","pmid":"33771569","tags":["venom-derived-peptides","peptide-engineering","neuroprotection"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Conkunitzin-C3 blocks Shaker K+ channels via a novel 'molecular lid' mechanism, using a non-conserved arginine to divert and trap permeating ions in cryptic sites above the selectivity filter.","whyItMatters":"Potassium channels are drug targets for heart rhythm disorders, pain, and neurological diseases. Discovering a new way peptides can block these channels expands the toolkit for designing channel-targeted therapeutics.","specificNumbers":"2 Kunitz peptides compared; 3 blocking modes described (plug, pore-collapse, lid); 1 non-conserved Arg residue is key; atomic-level description of lid mechanism","methodology":"Structural and biophysical study combining molecular modeling, electrophysiology, and structural analysis of two cone snail Kunitz-type peptides binding to Drosophila Shaker K+ channels.","limitations":"Used Drosophila Shaker channels, not human channels. Computational modeling was part of the analysis, which needs experimental validation. The clinical relevance of targeting this specific mechanism is not established."},{"rthcId":"RPEP-05736","title":"Applications of amphipathic and cationic cyclic cell-penetrating peptides: Significant therapeutic delivery tool.","authors":"Sajid, Muhammad Imran; Moazzam, Muhammad; Stueber, Ryan; Park, Shang Eun; Cho, Yeseom; Malik, Noor Ul Ain; Tiwari, Rakesh K","year":2021,"journal":"Peptides, 141, 170542","doi":"10.1016/j.peptides.2021.170542","pmid":"33794283","tags":["drug-delivery-systems","antimicrobial-peptides","peptide-engineering"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Cyclic cell-penetrating peptides demonstrate superior stability, cellular uptake, and endosomal escape compared to linear CPPs, with approximately 40 cyclic peptide therapeutics currently on the market.","whyItMatters":"Getting drugs into cells remains one of medicine's biggest challenges. Cyclic CPPs could deliver a wide range of therapeutics, including those for drug-resistant infections and cancer, that cannot enter cells on their own.","specificNumbers":"~40 cyclic peptide drugs marketed; ~1 new per year; applications in MDR infections, HIV, cancer; better stability, uptake, and endosomal escape than linear CPPs","methodology":"Comprehensive review of cationic and amphipathic cyclic cell-penetrating peptides, covering structures, mechanisms of translocation, and biomedical delivery applications.","limitations":"Review article covering a broad field. Clinical data on cyclic CPPs as delivery vehicles (vs as drugs themselves) is still limited. Manufacturing complexity and cost can be higher than linear peptides."},{"rthcId":"RPEP-05737","title":"Characterization of putative tachykinin peptides in Caenorhabditis elegans.","authors":"Sakai, Naoko; Ohno, Hayao; Yoshida, Morikatsu; Iwamoto, Eri; Kurogi, Akito; Jiang, Danfeng; Sato, Takahiro; Miyazato, Mikiya; Kojima, Masayasu; Kato, Johji; Ida, Takanori","year":2021,"journal":"Biochemical and biophysical research communications, 559, 197-202","doi":"10.1016/j.bbrc.2021.04.063","pmid":"33945998","tags":["neuropeptides","peptide-engineering","receptor-biology"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Three novel tachykinin-like peptides (CeTK-1, -2, -3) from the C. elegans nlp-58 gene potently activate the orphan GPCR TKR-1, sharing the C-terminal GLR-amide motif with other invertebrate tachykinins.","whyItMatters":"Understanding neuropeptide evolution across species helps identify conserved signaling pathways that may be relevant to human health. Tachykinins are involved in pain, inflammation, and mood in humans.","specificNumbers":"3 peptides (CeTK-1, -2, -3); 1 deorphanized receptor (TKR-1); C-terminal GLR-amide motif; restricted neuronal expression of nlp-58","methodology":"Unbiased biochemical screen identified NLP-58-derived peptides as TKR-1 agonists. Confirmed with receptor activation assays. Gene expression mapping showed restricted neuronal expression of nlp-58.","limitations":"C. elegans is a very simple organism. Findings may not directly translate to mammalian tachykinin biology. Functional roles of CeTK peptides in worm behavior were not tested in this study."},{"rthcId":"RPEP-05738","title":"Direct entry of cell-penetrating peptide can be controlled by maneuvering the membrane curvature.","authors":"Sakamoto, Kazutami; Morishita, Taku; Aburai, Kenichi; Ito, Daisuke; Imura, Tomohiro; Sakai, Kenichi; Abe, Masahiko; Nakase, Ikuhiko; Futaki, Shiroh; Sakai, Hideki","year":2021,"journal":"Scientific reports, 11(1), 31","doi":"10.1038/s41598-020-79518-1","pmid":"33420144","tags":["drug-delivery-systems","peptide-engineering","bioavailability"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Cell-penetrating peptide cytolysis occurs through dynamic phase transitions from lamellar to pored mesh structures, and can be controlled by manipulating membrane curvature via osmotic pressure.","whyItMatters":"Understanding exactly how CPPs cross membranes is essential for designing better drug delivery systems. If curvature is the key, then controlling curvature could improve how well peptide-based drugs get into target cells.","specificNumbers":"FITC-R8 as CPP; DOPC GUVs; Lα to Mesh1 phase transition; osmotic pressure modulation of curvature and entry","methodology":"Biophysical study using giant unilamellar vesicles (GUVs) made from DOPC as cell models. Fluorescently labeled octa-arginine (R8) used as CPP. Membrane curvature controlled via osmotic pressure. Phase behavior characterized by physical measurements.","limitations":"Used artificial vesicles, not real cells. DOPC is a simplified membrane model. Real cell membranes contain many different lipids, proteins, and structures that could affect results. Only one CPP (R8) was tested."},{"rthcId":"RPEP-05739","title":"Clinical Use of the Self-Assembling Peptide RADA16: A Review of Current and Future Trends in Biomedicine.","authors":"Sankar, Sharanya; O'Neill, Kate; Bagot D'Arc, Maurice; Rebeca, Florian; Buffier, Marie; Aleksi, Elton; Fan, Melanie; Matsuda, Noriaki; Gil, Eun Seok; Spirio, Lisa","year":2021,"journal":"Frontiers in bioengineering and biotechnology, 9, 679525","doi":"10.3389/fbioe.2021.679525","pmid":"34164387","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05740","title":"Identification of a crocodylian β-defensin variant from Alligator mississippiensis with antimicrobial and antibiofilm activity.","authors":"Santana, Felix L; Arenas, Iván; Haney, Evan F; Estrada, Karel; Hancock, Robert E W; Corzo, Gerardo","year":2021,"journal":"Peptides, 141, 170549","doi":"10.1016/j.peptides.2021.170549","pmid":"33865931","tags":["antimicrobial-peptides","immune-function","peptide-engineering"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Alligator beta-defensin variant Am23SK showed superior antimicrobial and antibiofilm activity against four bacterial pathogens compared to human beta-defensin 3, with no mammalian cell toxicity and immunomodulatory effects.","whyItMatters":"Antibiotic resistance is a global crisis, especially with biofilm-forming bacteria. Natural antimicrobial peptides from crocodilians could inspire new antibiotic designs that also reduce harmful inflammation.","specificNumbers":"5 defensin variants; Am23SK best performer; 4 bacteria tested (Salmonella, S. aureus, E. cloacae, A. baumannii); superior to human β-defensin 3; no cytotoxicity; suppressed pro-inflammatory mediators","methodology":"Lab study. Five crocodylian defensin variants synthesized and folded. Tested against Salmonella Typhimurium, S. aureus, E. cloacae, and A. baumannii in planktonic and biofilm assays. Cytotoxicity tested on mammalian cells. Immunomodulatory effects assessed in human bronchial epithelial cells.","limitations":"Lab study only. Activity was tested under specific experimental conditions that may not reflect clinical settings. No animal or human testing. Stability and delivery of the peptide in the body are not addressed."},{"rthcId":"RPEP-05741","title":"Reptilian β-defensins: Expanding the repertoire of known crocodylian peptides.","authors":"Santana, Felix L; Estrada, Karel; Ortiz, Ernesto; Corzo, Gerardo","year":2021,"journal":"Peptides, 136, 170473","doi":"10.1016/j.peptides.2020.170473","pmid":"33309943","tags":["antimicrobial-peptides","immune-function","peptide-engineering"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Reptilian beta-defensins have diversified through gene duplication and positive selection, show broad in vitro antimicrobial activity, but their in vivo functions and immunomodulatory roles require further investigation.","whyItMatters":"Reptiles have survived for hundreds of millions of years with robust innate immunity. Understanding their defensins could reveal new antimicrobial peptide structures and principles that apply across all vertebrates, including humans.","specificNumbers":"Gene organization similar to birds; variable gene numbers; duplication and positive selection; broad in vitro antimicrobial activity; in vivo roles uncharacterized","methodology":"Review of published literature on reptilian beta-defensin genomics, evolution, structure, and biological activity.","limitations":"Review of a field with limited experimental data. Most antimicrobial testing has been in vitro only. Very few reptilian defensins have been functionally characterized. Genomic data is incomplete for many species."},{"rthcId":"RPEP-05742","title":"Comparable Initial Engagement of Intracellular Signaling Pathways by Parathyroid Hormone Receptor Ligands Teriparatide, Abaloparatide, and Long-Acting PTH.","authors":"Sato, Tadatoshi; Verma, Shiv; Khatri, Ashok; Dean, Thomas; Goransson, Olga; Gardella, Thomas J; Wein, Marc N","year":2021,"journal":"JBMR plus, 5(5), e10441","doi":"10.1002/jbm4.10441","pmid":"33977197","tags":["bone-health","receptor-biology","peptide-engineering"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Teriparatide, abaloparatide, and LA-PTH showed comparable PTH1R downstream signaling (cAMP, calcium, SIK, gene expression) in vitro, with abaloparatide uniquely showing faster receptor recycling after washout.","whyItMatters":"Understanding why similar peptide drugs have different clinical effects is key to designing better bone therapies. If the difference is pharmacokinetic rather than signaling-based, it changes how we optimize these drugs.","specificNumbers":"3 ligands; no difference in cAMP, calcium, β-arrestin, SIK2, gene expression; abaloparatide faster receptor recycling; comparable at all tested concentrations","methodology":"Lab study comparing three PTH1R ligands across multiple cell-based signaling assays: receptor internalization, beta-arrestin recruitment, intracellular calcium, cAMP, SIK2 phosphorylation, substrate dephosphorylation, and gene expression changes.","limitations":"In vitro study only. Cell-based assays may not capture the full complexity of PTH1R signaling in bone cells in vivo. Only short-term signaling was measured. Pharmacokinetic differences were proposed but not tested."},{"rthcId":"RPEP-05743","title":"A host-directed macrocyclic peptide therapeutic for MDR gram negative bacterial infections.","authors":"Schaal, Justin B; Eriguchi, Yoshihiro; Tran, Dat Q; Tran, Patti A; Hawes, Chase; Cabebe, Anthony E; Pike, Kaitlyn; Trinh, Katie; Ouellette, André J; Selsted, Michael E","year":2021,"journal":"Scientific reports, 11(1), 23447","doi":"10.1038/s41598-021-02619-y","pmid":"34873199","tags":["antimicrobial-peptides","immune-function","drug-delivery-systems"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Macrocyclic peptide MTD-12813 rescued mice from lethal CRE sepsis through host-directed mechanisms: rapid immune-mediated bacterial clearance, cytokine modulation, and prevention of septic shock, without direct antibacterial activity.","whyItMatters":"Carbapenem-resistant bacteria are running out of treatment options. A host-directed peptide that boosts immune clearance rather than targeting bacteria directly could bypass resistance mechanisms entirely.","specificNumbers":"Single dose effective; significant survival improvement; no direct antibacterial activity in serum/peritoneal fluid; non-toxic at 100x dose; protease resistant; stable in biological matrices","methodology":"Animal study. Mouse septicemia models using carbapenem-resistant K. pneumoniae and E. coli. Single-dose MTD-12813 given. Measured survival, bacterial clearance, cytokine responses, direct antibacterial activity in serum/peritoneal fluid, stability, protease resistance, and toxicity.","limitations":"Animal study in mice only. The lack of direct antibacterial activity means it may not work in immunocompromised patients. Single-dose efficacy shown, but long-term or repeated dosing was not tested. Human immune responses may differ."},{"rthcId":"RPEP-05744","title":"Peptides and Antibiotic Therapy: Advances in Design and Delivery.","authors":"Schafer, Morgan E; Browne, Hailee; Goldberg, Joanna B; Greenberg, David E","year":2021,"journal":"Accounts of chemical research, 54(10), 2377-2385","doi":"10.1021/acs.accounts.1c00040","pmid":"33881843","tags":["antimicrobial-peptides","drug-delivery-systems","peptide-engineering"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Two major peptide-based antimicrobial strategies are emerging. First, novel modified antimicrobial peptides (AMPs) are being engineered to overcome traditional AMP limitations like instability and toxicity while maintaining antibacterial activity. Second, cell-penetrating peptides (CPPs) conjugated to phosphorodiamidate morpholino oligomers (PPMOs) can deliver gene-specific antimicrobials directly into gram-negative bacteria. PPMOs maintain activity against multidrug-resistant strains and show effectiveness in biofilm settings — two critical advantages over conventional antibiotics. Resistance development to these peptide approaches appears slower than to traditional antibiotics.","whyItMatters":"Antibiotic resistance is one of the most urgent public health threats, and the pipeline of new traditional antibiotics is running dry. Peptide-based approaches represent entirely new mechanisms that bacteria haven't developed resistance to, potentially giving medicine new tools in the fight against superbugs and difficult-to-treat biofilm infections.","specificNumbers":"2 approaches reviewed; PPMOs active vs MDR strains; active in biofilm settings; resistance development slower than traditional antibiotics","methodology":"The researchers conducted a review of current advances in two areas of peptide-based antibiotic research: direct-acting modified antimicrobial peptides and peptide-based delivery systems for antimicrobial compounds. They analyzed recent in vitro and in vivo data on peptide-conjugated PMOs (PPMOs), cell-penetrating peptide conjugates, and novel peptide designs.","limitations":"This is a review article without original experimental data. Many of the peptide antimicrobials discussed are still in preclinical development. Manufacturing costs remain high, and challenges around in vivo stability, potential toxicity, and pharmacokinetics have not been fully resolved. Clinical trial data for most approaches is limited or nonexistent."},{"rthcId":"RPEP-05745","title":"CGRP antibody therapy in patients with drug resistant migraine and chronic daily headache: a real-world experience.","authors":"Scheffler, Armin; Schenk, Hannah; Wurthmann, Sebastian; Nsaka, Michael; Kleinschnitz, Christoph; Glas, Martin; Holle, Dagny","year":2021,"journal":"The journal of headache and pain, 22(1), 111","doi":"10.1186/s10194-021-01323-6","pmid":"34544359","tags":["neuropeptides","clinical-applications","pain-management"],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"CGRP antibodies reduced monthly headache days by 4.2 and migraine days by 4.3 in patients with drug-resistant daily headache, with 13% achieving 50% headache reduction and 25% achieving 50% migraine reduction.","whyItMatters":"Patients with daily drug-resistant headache have very few options. Even modest improvement in these severely affected patients represents meaningful quality of life gains.","specificNumbers":"32 patients; 3 months; MHD reduced 4.2 (p=0.009); MMD reduced 4.3 (p=0.033); 50% responder: 13% MHD, 25% MMD; 16 erenumab, 7 galcanezumab, 9 fremanezumab","methodology":"Retrospective analysis of clinical routine data from 32 patients with daily headache and drug-resistant migraine treated with CGRP antibodies (16 erenumab, 7 galcanezumab, 9 fremanezumab) for 3 months.","limitations":"Retrospective design with only 32 patients. No control group. Three-month follow-up may be too short for some patients to respond fully. Mixed antibody types used without head-to-head comparison."},{"rthcId":"RPEP-05746","title":"Sodium Bituminosulfonate Used to Treat Rosacea Modulates Generation of Inflammatory Mediators by Primary Human Neutrophils.","authors":"Schiffmann, Susanne; Gunne, Sandra; Henke, Marina; Ulshöfer, Thomas; Steinhilber, Dieter; Sethmann, Annette; Parnham, Michael J","year":2021,"journal":"Journal of inflammation research, 14, 2569-2582","doi":"10.2147/JIR.S313636","pmid":"34163212","tags":["antimicrobial-peptides","inflammation","skin-health"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"SBDS reduces LL-37 release from neutrophils and inhibits KLK5 (IC50 7.6 µg/mL) and 5-lipoxygenase (IC50 33 µg/mL), disrupting the LTB4/LL-37/calcium inflammatory axis driving rosacea.","whyItMatters":"Rosacea affects millions and is driven by antimicrobial peptide overproduction. Understanding exactly how SBDS works could lead to better-targeted treatments and new approaches based on controlling LL-37 levels.","specificNumbers":"KLK5 IC50: 7.6 µg/mL; 5-LO IC50: 33 µg/mL; reduced LL-37, calcium, ROS, VEGF, elastase from neutrophils","methodology":"Lab study using primary human neutrophils. Measured LL-37, calcium, elastase, ROS, VEGF release, and cytokine expression. Tested enzyme inhibition of KLK5, MMP9, and 5-lipoxygenase with recombinant proteins.","limitations":"Lab study using isolated neutrophils, not intact skin. The proposed mechanism (LTB4/LL-37/calcium axis) is a hypothesis that needs in vivo confirmation. SBDS may have additional mechanisms not captured in this study."},{"rthcId":"RPEP-05747","title":"MUG Mel3 Cell Lines Reflect Heterogeneity in Melanoma and Represent a Robust Model for Melanoma in Pregnancy.","authors":"Schrom, Silke; Hebesberger, Thomas; Wallner, Stefanie Angela; Anders, Ines; Richtig, Erika; Brandl, Waltraud; Hirschmugl, Birgit; Garofalo, Mariangela; Bernecker, Claudia; Schlenke, Peter; Kashofer, Karl; Wadsack, Christian; Aigelsreiter, Ariane; Heitzer, Ellen; Riedl, Sabrina; Zweytick, Dagmar; Kretschmer, Nadine; Richtig, Georg; Rinner, Beate","year":2021,"journal":"International journal of molecular sciences, 22(21)","doi":"10.3390/ijms222111318","pmid":"34768746","tags":["cancer-research","antimicrobial-peptides","lactoferrin"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Four melanoma cell lines (MUG Mel3) were established from pigmented and non-pigmented sections of a lymph node metastasis from a pregnant patient, cultured under different conditions. Each line exhibited distinct phenotypic, genotypic, and tumorigenic properties — all carrying BRAF mutations — demonstrating melanoma's inherent heterogeneity.\n\nSynthetic human lactoferricin-derived peptides were tested against all four cell lines and showed effective anti-tumor activity across the board. This is significant because the peptides worked despite the considerable heterogeneity between cell lines, suggesting broad applicability against diverse melanoma cell populations.","whyItMatters":"Melanoma is one of the most common cancers diagnosed during pregnancy, and treatment options are severely limited by the need to protect the fetus. Anti-tumor peptides derived from lactoferricin — a natural component of breast milk — could provide a fundamentally different treatment approach with potentially better safety profiles for pregnant patients. Additionally, the four heterogeneous cell lines serve as a valuable research model for studying melanoma diversity and drug resistance.","specificNumbers":"4 cell lines; BRAF-mutated; different phenotypic and tumorigenic properties; lactoferricin peptides effective across all lines","methodology":"A lymph node metastasis was obtained from a pregnant melanoma patient. Pigmented and non-pigmented sections were cultured under different laboratory conditions, yielding four distinct cell lines. Each line was comprehensively characterized for phenotypic properties, genetic mutations, and tumor-forming ability (including xenograft models in mice). Synthetic lactoferricin-derived peptides were then tested for anti-tumor effectiveness against all four lines.","limitations":"This is entirely a laboratory study — peptide effectiveness was demonstrated in cell culture and mouse xenografts, not in pregnant humans or animals. The safety of lactoferricin-derived peptides during pregnancy has not been tested. All four cell lines came from a single patient's tumor, which may not represent the full spectrum of melanoma diversity. The study does not compare peptide efficacy to standard melanoma therapies."},{"rthcId":"RPEP-05748","title":"Stable Gastric Pentadecapeptide BPC 157 and Wound Healing.","authors":"Seiwerth, Sven; Milavic, Marija; Vukojevic, Jaksa; Gojkovic, Slaven; Krezic, Ivan; Vuletic, Lovorka Batelja; Pavlov, Katarina Horvat; Petrovic, Andrea; Sikiric, Suncana; Vranes, Hrvoje; Prtoric, Andreja; Zizek, Helena; Durasin, Tajana; Dobric, Ivan; Staresinic, Mario; Strbe, Sanja; Knezevic, Mario; Sola, Marija; Kokot, Antonio; Sever, Marko; Lovric, Eva; Skrtic, Anita; Blagaic, Alenka Boban; Sikiric, Predrag","year":2021,"journal":"Frontiers in pharmacology, 12, 627533","doi":"10.3389/fphar.2021.627533","pmid":"34267654","tags":["bpc-157","wound-healing","tissue-repair"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"BPC-157 promotes wound healing across virtually all tissue types through vessel regulation, clot management, and rapid gene expression activation, effective at both µg and ng doses via oral or injectable routes.","whyItMatters":"A single peptide that promotes healing across so many tissue types through common mechanisms could have wide therapeutic applications, from surgical recovery to chronic wound management.","specificNumbers":"No reported toxicity; LD1 not achieved; effective at µg and ng doses; oral and injectable routes equipotent; heals skin, gut, tendon, ligament, muscle, bone, nerve, spinal cord, cornea, blood vessels","methodology":"Comprehensive review of animal studies on BPC-157 wound healing, covering skin wounds, fistulas, burns, diabetic ulcers, and multiple internal tissue types.","limitations":"Based almost entirely on animal studies. Clinical trial data is limited to ulcerative colitis and multiple sclerosis. No large randomized controlled trials for wound healing in humans. Many studies come from the same research group."},{"rthcId":"RPEP-05749","title":"Plasma mitochondrial derived peptides MOTS-c and SHLP2 positively associate with android and liver fat in people without diabetes.","authors":"Sequeira, Ivana R; Woodhead, Jonathan S T; Chan, Alex; D'Souza, Randall F; Wan, Junxiang; Hollingsworth, Kieren G; Plank, Lindsay D; Cohen, Pinchas; Poppitt, Sally D; Merry, Troy L","year":2021,"journal":"Biochimica et biophysica acta. General subjects, 1865(11), 129991","doi":"10.1016/j.bbagen.2021.129991","pmid":"34419510","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05750","title":"Spray Freeze Dried Lyospheres® for Nasal Administration of Insulin.","authors":"Serim, Tuğrul Mert; Kožák, Jan; Rautenberg, Annika; Özdemir, Ayşe Nurten; Pellequer, Yann; Lamprecht, Alf","year":2021,"journal":"Pharmaceutics, 13(6)","doi":"10.3390/pharmaceutics13060852","pmid":"34201254","tags":["drug-delivery-systems","insulin-regulation","bioavailability"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Spray freeze-dried lyospheres with sodium taurocholate achieved 7.0% nasal bioavailability of insulin in rats, with 90%+ nasal deposition and rapid dissolution due to high porosity and low density.","whyItMatters":"Insulin injections are the biggest burden for many diabetes patients. A nasal delivery system that achieves meaningful bioavailability could transform diabetes management for millions of people.","specificNumbers":"7.0 ± 2.8% insulin bioavailability; 90%+ nasal deposition; 190-250 µm particles; dextran absorption: 0.7% (70 kDa) to 10.0% (4 kDa)","methodology":"Formulation study. Insulin solutions with excipients spray-frozen and freeze-dried. Characterized particle size (190-250 µm), porosity, and deposition. Tested in vivo glycemic effect in rats. Absorption tested with fluorescent dextrans of various molecular weights.","limitations":"Animal study in rats. Nasal anatomy and absorption in humans differ significantly. 7% bioavailability would require higher doses and may have cost implications. Sodium taurocholate may cause nasal irritation with repeated use. Long-term stability data not provided."},{"rthcId":"RPEP-05751","title":"Dietary habits in Japanese patients with palmoplantar pustulosis.","authors":"Serizawa, Naotaka; Okazaki, Shizuka; Otsuka, Yohei; Koto, Mototaka; Okabe, Kyochika; Ito, Michiko; Morita, Takashi; Hoashi, Toshihiko; Saeki, Hidehisa; Abe, Namiko; Mori, Miho; Okubo, Yukari; Yano, Yumiko; Mitsui, Hiroshi; Kanda, Naoko","year":2021,"journal":"The Journal of dermatology, 48(3), 366-375","doi":"10.1111/1346-8138.15719","pmid":"33404125","tags":["antimicrobial-peptides","inflammation","skin-health"],"studyType":"observational","evidenceStrength":"preliminary","keyFinding":"PPP patients showed higher BMI, more pulse/sugar intake, and less vitamin A than controls, with sodium intake and BMI predicting disease severity (PPPASI scores).","whyItMatters":"If diet influences PPP through inflammatory peptide pathways, dietary intervention could complement existing treatments. Understanding these connections could help patients manage their condition.","specificNumbers":"Higher BMI, pulses, sugar in PPP; lower vitamin A; sodium and BMI predict PPPASI; PAO patients younger with lower sodium; first dietary study in PPP","methodology":"Cross-sectional study comparing dietary habits of Japanese PPP patients to age/sex-matched healthy controls using a validated diet questionnaire. Disease severity assessed by PPPASI. Logistic and linear regression analyses performed.","limitations":"Cross-sectional design cannot prove causation. Japanese population results may not generalize to other ethnicities. Self-reported dietary data has inherent biases. Specific sample sizes not stated in abstract."},{"rthcId":"RPEP-05752","title":"Exendin-4-based imaging in insulinoma localization: Systematic review and meta-analysis.","authors":"Shah, Ravikumar; Garg, Robin; Majmundar, Monil; Purandare, Nilendu; Malhotra, Gaurav; Patil, Virendra; Ramteke-Jadhav, Swati; Lila, Anurag; Shah, Nalini; Bandgar, Tushar","year":2021,"journal":"Clinical endocrinology, 95(2), 354-364","doi":"10.1111/cen.14406","pmid":"33386617","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05753","title":"A Venomics Approach to the Identification and Characterization of Bioactive Peptides From Animal Venoms for Colorectal Cancer Therapy: Protocol for a Proof-of-Concept Study.","authors":"Shahzadi, Syeda Kiran; Karuvantevida, Noushad; Banerjee, Yajnavalka","year":2021,"journal":"JMIR research protocols, 10(12), e31128","doi":"10.2196/31128","pmid":"34932002","tags":["venom-derived-peptides","cancer-research","peptide-engineering"],"studyType":"other","evidenceStrength":"preliminary","keyFinding":"Protocol describes high-throughput screening of 2,500 peptides from 20 animal venoms against colorectal cancer cell lines, with plans to isolate and characterize the most potent anti-CRC peptides.","whyItMatters":"Colorectal cancer is a leading cause of cancer death. Current treatments have significant side effects. Venom-derived peptides could provide targeted cancer-killing agents with different mechanisms than existing drugs.","specificNumbers":"2,500 peptides; 20 venoms; 3 CRC cell lines; 2 control cell lines; MTT assay; top 3 venoms for peptide isolation","methodology":"Proof-of-concept protocol. Will screen 2,500 peptides from 20 venoms using MTT cytotoxicity assay against 3 CRC cell lines and 2 control cell lines. Top 3 venoms will be further fractionated to identify specific anti-cancer peptides.","limitations":"Protocol only. No results available. Cell line screening does not predict clinical efficacy. The specificity of venom peptides in living organisms may differ from cell culture results."},{"rthcId":"RPEP-05754","title":"LEAP2 deletion in mice enhances ghrelin's actions as an orexigen and growth hormone secretagogue.","authors":"Shankar, Kripa; Metzger, Nathan P; Singh, Omprakash; Mani, Bharath K; Osborne-Lawrence, Sherri; Varshney, Salil; Gupta, Deepali; Ogden, Sean B; Takemi, Shota; Richard, Corine P; Nandy, Karabi; Liu, Chen; Zigman, Jeffrey M","year":2021,"journal":"Molecular metabolism, 53, 101327","doi":"10.1016/j.molmet.2021.101327","pmid":"34428557","tags":["appetite-regulation","growth-hormone-secretagogues","weight-management"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"LEAP2 deletion sensitized mice to ghrelin's orexigenic and GH-releasing effects, with LEAP2-KO females on high-fat diet showing 15% more body weight, 18% more food intake, 42% more hepatic fat, and increased body length.","whyItMatters":"LEAP2 acts as a natural brake on ghrelin signaling. Understanding this balance could lead to new treatments for obesity (boosting LEAP2) or wasting conditions (blocking LEAP2 to increase appetite).","specificNumbers":"Ghrelin sensitivity: 2x in lean, 10x in obese; GH 90.9% higher; c-fos 77-120% higher in arcuate/olfactory; females HFD: +15% weight, +18% food, +42% liver fat, +1.7% length, -13% O2, -9.5% heat, -49% locomotion","methodology":"Generated first LEAP2-KO mouse line. Tested ghrelin-stimulated food intake, GH secretion, and brain c-fos activation. Monitored body weight, composition, energy expenditure, and locomotor activity over 16 weeks on high-fat or standard diet.","limitations":"Animal study in mice. Sex-specific effects (mainly in females) may complicate translation. High-fat diet effects were more pronounced than standard diet effects. Complete LEAP2 deletion is more extreme than physiological variation."},{"rthcId":"RPEP-05755","title":"Clinical Applications of Substance P (Neurokinin-1 Receptor) Antagonist in Canine Medicine.","authors":"Sharun, K; Jambagi, K; Arya, M; Aakanksha; Chaithra, S N; Patel, P K; Dixit, S K; Dhama, K","year":2021,"journal":"Archives of Razi Institute, 76(5), 1175-1182","doi":"10.22092/ari.2021.356171.1797","pmid":"35355772","tags":["neuropeptides","clinical-applications","pain-management"],"studyType":"systematic-review","evidenceStrength":"moderate","keyFinding":"Maropitant is a broad-spectrum antiemetic in dogs effective against vomiting from pancreatitis, gastritis, parvovirus, chemotherapy, and kidney disease, with additional anesthetic-sparing and potential analgesic properties.","whyItMatters":"Substance P and NK-1 receptors are targets in both veterinary and human medicine. Understanding maropitant's broad effects in dogs provides insights relevant to developing NK-1 antagonists for human conditions.","specificNumbers":"173 articles screened; 41 selected; effective for pancreatitis, gastritis, parvovirus, chemo, uremic vomiting; reduces isoflurane requirement; injection pain from metacresol preservative","methodology":"Systematic literature review of 41 articles from 2001-2021 selected from 173 initial results across PubMed, ScienceDirect, Scopus, and Google Scholar.","limitations":"Veterinary-focused review. Results may not directly translate to human medicine. Some therapeutic claims (pain management) need more controlled studies. Review limited to canine applications."},{"rthcId":"RPEP-05756","title":"Generation and characterization of HLA-A2 transgenic mice expressing the human TCR 1G4 specific for the HLA-A2 restricted NY-ESO-1157-165 tumor-specific peptide.","authors":"Shenderov, Eugene; Kandasamy, Matheswaran; Gileadi, Uzi; Chen, Jili; Shepherd, Dawn; Gibbs, James; Prota, Gennaro; Silk, Jonathan D; Yewdell, Jonathan W; Cerundolo, Vincenzo","year":2021,"journal":"Journal for immunotherapy of cancer, 9(6)","doi":"10.1136/jitc-2021-002544","pmid":"34088742","tags":["cancer-research","immune-function","peptide-engineering"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"1G4 TCR transgenic mice produced T cells that specifically recognized NY-ESO-1 peptide, controlled tumor growth in adoptive transfer and direct challenge models, providing a platform for cancer vaccine and cell therapy development.","whyItMatters":"NY-ESO-1 is one of the most promising cancer vaccine targets. Having a mouse model with a human-like immune response to this antigen accelerates the testing and optimization of cancer immunotherapies before human trials.","specificNumbers":"1G4 TCR on CD4+ and CD8+ cells; no autoimmune reactivity; specific activation by NY-ESO-1 peptide; tumor control via adoptive transfer and direct challenge; tunable with altered peptide ligand","methodology":"Generated HLA-A*0201 transgenic mice encoding the 1G4 TCR. Tested T cell activation (proliferation, CD69, IFN-gamma, IL-2), antigen specificity, and tumor control in adoptive transfer and direct tumor challenge models.","limitations":"Mouse model cannot fully replicate human immune complexity. The tumor microenvironment in mice differs from humans. Only one TCR specificity tested. HLA-A*0201 restricted, so only applicable to that HLA type."},{"rthcId":"RPEP-05757","title":"Network meta-analysis on efficacy and safety of different anti-CGRP monoclonal antibody regimens for prophylaxis and treatment of episodic migraine.","authors":"Shi, Min; Guo, Jun; Li, Zhaoying; Sun, Honghui; Yang, Xuhong; Yang, Dongdong; Zhao, Huan","year":2021,"journal":"Neurological research, 43(11), 932-949","doi":"10.1080/01616412.2021.1940672","pmid":"34281473","tags":["neuropeptides","clinical-applications","pain-management"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Network meta-analysis of 11 RCTs (6,397 patients) ranked fremanezumab 225 mg and galcanezumab 120 mg as the best CGRP antibody regimens for episodic migraine prevention after comprehensive assessment.","whyItMatters":"Doctors need guidance on which CGRP antibody and dose to prescribe. This analysis provides the first comprehensive ranking across all available options, helping inform clinical decisions.","specificNumbers":"11 RCTs; 6,397 patients; 10 regimens; fremanezumab 225 mg and galcanezumab 120 mg ranked best; fremanezumab superior to erenumab 21/70 mg for migraine days","methodology":"Network meta-analysis of 11 randomized controlled trials comparing 10 anti-CGRP monoclonal antibody regimens (different drugs, doses, and routes) for episodic migraine. Searched PubMed, Embase, Ovid MEDLINE, Web of Science, and Cochrane.","limitations":"Network meta-analysis makes indirect comparisons between drugs not tested head-to-head. Study heterogeneity may affect results. Only episodic migraine included (not chronic). Follow-up periods varied across trials."},{"rthcId":"RPEP-05758","title":"Collagen-binding peptide reverses bone loss in a mouse model of cerebral palsy based on clinical databases.","authors":"Shin, Yoon-Kyum; Heo, Jeong Hyun; Lee, Jue Yeon; Park, Yoon-Jeong; Cho, Sung-Rae","year":2021,"journal":"Annals of physical and rehabilitation medicine, 64(3), 101445","doi":"10.1016/j.rehab.2020.09.009","pmid":"33130040","tags":["bone-health","peptide-engineering","clinical-applications"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Collagen-binding peptide increased trabecular thickness, collagen content, and osteoblast differentiation markers (RUNX2, osteocalcin) in a CP mouse model developed from clinical transcriptome analysis of 119 CP patients.","whyItMatters":"Bone loss in cerebral palsy causes fractures and pain but has no approved drug treatment. A peptide that directly stimulates bone building could fill this critical gap.","specificNumbers":"119 CP patients; SPP1 downregulated; 140 mice; CBP increased trabecular thickness, collagen, bone turnover; RUNX2 and osteocalcin upregulated vs saline","methodology":"Translational study: transcriptome analysis of 119 CP patients and 13 healthy controls, development of a hypoxic-ischemic brain injury CP mouse model (140 mice), and testing of collagen-binding peptide vs saline control.","limitations":"Mouse model may not fully replicate human CP bone loss. The collagen-binding peptide was tested only short-term. No comparison to existing osteoporosis drugs. Human clinical trials are needed."},{"rthcId":"RPEP-05759","title":"Anti-angiogenic peptides application in cancer therapy; a review.","authors":"Shoari, Alireza; Khodabakhsh, Farnaz; Ahangari Cohan, Reza; Salimian, Morteza; Karami, Elmira","year":2021,"journal":"Research in pharmaceutical sciences, 16(6), 559-574","doi":"10.4103/1735-5362.327503","pmid":"34760005","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05760","title":"The possible double-edged sword effects of vitamin D on COVID-19: A hypothesis.","authors":"Shojaeefar, Ehsan; Malih, Narges; Rezaei, Nima","year":2021,"journal":"Cell biology international, 45(1), 54-57","doi":"10.1002/cbin.11469","pmid":"32990980","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05761","title":"Angiogenic hydrogels for dental pulp revascularization.","authors":"Siddiqui, Zain; Sarkar, Biplab; Kim, Ka-Kyung; Kadincesme, Nurten; Paul, Reshma; Kumar, Arjun; Kobayashi, Yoshifumi; Roy, Abhishek; Choudhury, Marwa; Yang, Jian; Shimizu, Emi; Kumar, Vivek A","year":2021,"journal":"Acta biomaterialia, 126, 109-118","doi":"10.1016/j.actbio.2021.03.001","pmid":"33689817","tags":["peptide-scaffolds","tissue-repair","wound-healing"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Acellular self-assembling peptide hydrogel regenerated vascularized pulp-like tissue with blood vessels, neural filaments, and an odontoblast-like layer in a canine orthotopic model without added growth factors.","whyItMatters":"Root canals leave teeth without living tissue, making them brittle and prone to failure. Regenerating actual pulp tissue inside teeth could preserve tooth vitality and longevity, benefiting millions of dental patients.","specificNumbers":"Acellular injectable gel; no growth factors; blood vessels, neural filaments, odontoblast-like layer regenerated; tissue resembled native pulp","methodology":"Large animal (canine) orthotopic study. Self-assembling peptide hydrogels injected into teeth after pulpectomy. Assessed tissue regeneration including vasculature, nerve fibers, and odontoblast-like cells.","limitations":"Dog model, not human. Long-term outcomes not reported. The quality and function of regenerated tissue compared to native pulp needs more assessment. Applicability to human teeth with different anatomy and infection history is unclear."},{"rthcId":"RPEP-05762","title":"Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder.","authors":"Sikich, Linmarie; Kolevzon, Alexander; King, Bryan H; McDougle, Christopher J; Sanders, Kevin B; Kim, Soo-Jeong; Spanos, Marina; Chandrasekhar, Tara; Trelles, M D Pilar; Rockhill, Carol M; Palumbo, Michelle L; Witters Cundiff, Allyson; Montgomery, Alicia; Siper, Paige; Minjarez, Mendy; Nowinski, Lisa A; Marler, Sarah; Shuffrey, Lauren C; Alderman, Cheryl; Weissman, Jordana; Zappone, Brooke; Mullett, Jennifer E; Crosson, Hope; Hong, Natalie; Siecinski, Stephen K; Giamberardino, Stephanie N; Luo, Sheng; She, Lilin; Bhapkar, Manjushri; Dean, Russell; Scheer, Abby; Johnson, Jacqueline L; Gregory, Simon G; Veenstra-VanderWeele, Jeremy","year":2021,"journal":"The New England journal of medicine, 385(16), 1462-1473","doi":"10.1056/NEJMoa2103583","pmid":"34644471","tags":["neuropeptides","clinical-applications","mental-health"],"studyType":"randomized-controlled-trial","evidenceStrength":"strong","keyFinding":"Intranasal oxytocin (48 IU daily for 24 weeks) showed no significant improvement in social withdrawal (ABC-mSW: -3.7 vs -3.5 placebo, p=0.61) or secondary outcomes in 290 children with autism.","whyItMatters":"Oxytocin has been widely hyped and even prescribed off-label for autism despite limited evidence. This large, well-designed trial shows it does not work for this purpose, which should change clinical practice.","specificNumbers":"290 enrolled; 146 oxytocin, 144 placebo; 24 weeks; 48 IU daily; ABC-mSW: -3.7 vs -3.5 (p=0.61); no secondary differences; similar adverse events","methodology":"Phase 2, double-blind, placebo-controlled, randomized trial. 290 children and adolescents (3-17 years) with ASD. 1:1 randomization stratified by age and verbal fluency. 48 IU intranasal oxytocin or placebo daily for 24 weeks. Primary: ABC-mSW. Secondary: social function and IQ measures.","limitations":"Single dose level tested (48 IU). Some patients may respond to different doses or have subtypes of autism more responsive to oxytocin. 24 weeks may not capture very long-term effects. Both groups improved, suggesting strong placebo effects."},{"rthcId":"RPEP-05763","title":"Impact of glucagon-like peptide-1 receptor agonists on adiponectin concentrations: A meta-analysis of randomized controlled trials.","authors":"Simental-Mendía, Luis E; Sánchez-García, Adriana; Linden-Torres, Enrique; Simental-Mendía, Mario","year":2021,"journal":"British journal of clinical pharmacology, 87(11), 4140-4149","doi":"10.1111/bcp.14855","pmid":"33835520","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05764","title":"Efficacy of Cathelicidin LL-37 in an MRSA Wound Infection Mouse Model.","authors":"Simonetti, Oriana; Cirioni, Oscar; Goteri, Gaia; Lucarini, Guendalina; Kamysz, Elżbieta; Kamysz, Wojciech; Orlando, Fiorenza; Rizzetto, Giulio; Molinelli, Elisa; Morroni, Gianluca; Ghiselli, Roberto; Provinciali, Mauro; Giacometti, Andrea; Offidani, Annamaria","year":2021,"journal":"Antibiotics (Basel, Switzerland), 10(10)","doi":"10.3390/antibiotics10101210","pmid":"34680791","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05765","title":"Investigation of serum beta-defensin-1 levels in bovine trichophytosis cases.","authors":"Simsek, Aynur","year":2021,"journal":"Veterinary world, 14(9), 2508-2511","doi":"10.14202/vetworld.2021.2508-2511","pmid":"34840471","tags":["antimicrobial-peptides","immune-function"],"studyType":"observational","evidenceStrength":"preliminary","keyFinding":"Serum beta-defensin-1 levels were slightly lower in cattle with trichophytosis compared to healthy controls, but the difference was not statistically significant (p>0.05).","whyItMatters":"Understanding whether antimicrobial peptides respond to fungal infections could reveal innate immune mechanisms and potential biomarkers, even though this study found no significant change.","specificNumbers":"23 cattle; 16 infected, 7 healthy; serum beta-defensin-1 lower in infected group; p>0.05 not significant","methodology":"Observational study. 23 young cattle (2-4 months): 16 with clinical trichophytosis and 7 healthy controls. Measured serum beta-defensin-1 levels.","limitations":"Very small sample size (23 cattle total, only 7 controls). Serum levels may not reflect local defensin activity in infected skin. Only beta-defensin-1 was measured; other defensins might respond differently."},{"rthcId":"RPEP-05766","title":"Novel Anthracycline Utorubicin for Cancer Therapy.","authors":"Simón-Gracia, Lorena; Sidorenko, Valeria; Uustare, Ain; Ogibalov, Ivan; Tasa, Andrus; Tshubrik, Olga; Teesalu, Tambet","year":2021,"journal":"Angewandte Chemie (International ed. in English), 60(31), 17018-17027","doi":"10.1002/anie.202016421","pmid":"33908690","tags":["cancer-research","drug-delivery-systems","peptide-engineering"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Free Utorubicin was significantly more cytotoxic to cultured tumor cell lines than doxorubicin, the most widely used anthracycline in clinical oncology. When encapsulated in polymersomes (PS), UTO reduced malignant cell viability, and this effect was further enhanced by functionalization with a tumor-penetrating peptide (TPP).\n\nIn triple-negative breast cancer xenograft mice, systemic administration showed a clear hierarchy of tumor accumulation at equivalent UTO doses: TPP-targeted polymersomes > non-targeted polymersomes > free doxorubicin. The peptide-guided nanoparticles showed preferential accumulation in the tumor tissue, demonstrating successful precision delivery.","whyItMatters":"Triple-negative breast cancer is the most aggressive and treatment-resistant breast cancer subtype, with limited targeted therapy options. Doxorubicin remains a frontline treatment but is limited by cardiotoxicity and modest tumor penetration. A more potent anthracycline delivered by tumor-penetrating peptides could improve both efficacy and safety — hitting the tumor harder while reducing exposure to the heart and other organs.","specificNumbers":"UTO more cytotoxic than doxorubicin; TPP-polymersomes > nontargeted PS > free doxorubicin for tumor accumulation; triple-negative breast cancer model","methodology":"UTO was synthesized as a novel anthracycline and characterized for anticancer activity. Cytotoxicity was compared to doxorubicin across multiple tumor cell lines. UTO was encapsulated in polymersomes (polymeric nanovesicles), with and without tumor-penetrating peptide surface functionalization. Tumor accumulation and efficacy were assessed in mice bearing triple-negative breast cancer xenografts following systemic (intravenous) administration. Drug distribution was quantified by optical imaging and tissue analysis.","limitations":"This is a preclinical study using mouse xenograft models that don't fully replicate human tumor heterogeneity and immune responses. The full toxicity profile of UTO (particularly cardiotoxicity, a major concern with anthracyclines) was not characterized. Long-term efficacy, survival data, and dose-limiting toxicities were not reported. The comparison was between tumor accumulation, not treatment outcomes."},{"rthcId":"RPEP-05767","title":"Intracellular delivery of oxaliplatin conjugate via cell penetrating peptide for the treatment of colorectal carcinoma in vitro and in vivo.","authors":"Singh, Tejinder; Kang, Dong Hyun; Kim, Tae Wan; Kong, Hye Jeong; Ryu, Jae Sung; Jeon, Seob; Ahn, Tae Sung; Jeong, Dongjun; Baek, Moo Jun; Im, Jungkyun","year":2021,"journal":"International journal of pharmaceutics, 606, 120904","doi":"10.1016/j.ijpharm.2021.120904","pmid":"34293467","tags":["drug-delivery-systems","cancer-research","peptide-engineering"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Octa-arginine CPP-oxaliplatin conjugate showed mitochondrial targeting, achieved IC50 at much lower concentrations than oxaliplatin alone in vitro, and effectively inhibited tumor growth in a mouse colon cancer model.","whyItMatters":"Oxaliplatin resistance and dose-limiting side effects are major barriers in colorectal cancer treatment. Delivering it more efficiently into cancer cells could overcome resistance and allow lower, safer doses.","specificNumbers":"R8-oxaliplatin conjugate; mitochondrial affinity; IC50 much lower than oxaliplatin alone; effective tumor growth inhibition in vivo","methodology":"Synthesized R8-oxaliplatin conjugate via heterobifunctional linker. Tested cellular uptake, mitochondrial localization, cytotoxicity (MTT assay), and in vivo tumor growth inhibition in a mouse colon cancer model.","limitations":"Preclinical study. Mouse model may not predict human response. Long-term toxicity of the conjugate not assessed. Manufacturing and stability of peptide-drug conjugates can be challenging at scale."},{"rthcId":"RPEP-05768","title":"Recombinant expression of computationally designed peptide-bundlemers in Escherichia coli.","authors":"Sinha, Nairiti J; Kloxin, Christopher J; Saven, Jeffery G; Jensen, Grethe V; Kelman, Zvi; Pochan, Darrin J","year":2021,"journal":"Journal of biotechnology, 330, 57-60","doi":"10.1016/j.jbiotec.2021.03.004","pmid":"33689866","tags":["peptide-engineering","peptide-scaffolds","manufacturing"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"A 31-amino acid computationally designed bundlemer peptide was recombinantly expressed in E. coli at yields of 10 mg per liter, demonstrating a scalable alternative to solid-phase chemical synthesis.","whyItMatters":"Scaling up production of designed peptides is a major bottleneck. Showing that bacteria can make these building blocks economically opens up manufacturing pathways for peptide-based nanomaterials and biomaterials.","specificNumbers":"31 amino acids; 10 mg/L yield; E. coli expression; enables isotope labeling; complementary to SPPS","methodology":"Recombinant expression protocol. Computationally designed bundlemer peptide gene cloned and expressed in E. coli. Peptide purified and characterized. Yield: 10 mg/L media.","limitations":"Yield of 10 mg/L is adequate for research but may need optimization for industrial production. Only one peptide sequence tested. Not all computationally designed peptides may express well in bacteria."},{"rthcId":"RPEP-05769","title":"Supramolecular Structures Generated via Self-Assembly of a Cell Penetrating Tetrapeptide Facilitate Intracellular Delivery of a Pro-apoptotic Chemotherapeutic Drug.","authors":"Sivagnanam, Subramaniyam; Basak, Madhuri; Kumar, Abilesh; Das, Kiran; Mahata, Tarun; Rana, Priya; Sengar, Abhishek Singh; Ghosh, Soumyajit; Subramanian, Mahesh; Stewart, Adele; Maity, Biswanath; Das, Priyadip","year":2021,"journal":"ACS applied bio materials, 4(9), 6807-6820","doi":"10.1021/acsabm.1c00530","pmid":"35006981","tags":["drug-delivery-systems","cancer-research","peptide-engineering"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Self-assembling KVAV tetrapeptide formed spherical nanoparticles that encapsulated doxorubicin and delivered it intracellularly, inducing RGS6/Gβ5/ATM/p53-dependent apoptosis identical to free drug.","whyItMatters":"Ultra-short peptides that self-assemble into drug carriers are simpler and cheaper to make than complex nanoparticles. If they can reliably deliver cancer drugs while maintaining the drug's mechanism of action, they could become practical delivery platforms.","specificNumbers":"KVAV tetrapeptide; L1 (BOC-protected) and L2 (deprotected); spherical nanoparticles in 1:1 aqueous ethanol; RGS6/Gβ5 upregulated; ATM/p53 apoptosis confirmed; knockdown abolished effect","methodology":"Lab study. Synthesized BOC-protected (L1) and deprotected (L2) KVAV peptides. Characterized self-assembly. Encapsulated doxorubicin. Tested cellular uptake, viability, DNA damage, oxidative stress, mitochondrial function, and apoptosis. Used RGS6/Gβ5 knockdown to confirm mechanism.","limitations":"Lab study only. No animal testing. Only one drug (doxorubicin) tested. The nanoparticle stability, pharmacokinetics, and tumor targeting in vivo are unknown. Selectivity for cancer vs normal cells not assessed."},{"rthcId":"RPEP-05770","title":"Role of GLP-1 Analogs in the Management of Diabetes and its Secondary Complication.","authors":"Sivakumar, Ponnurengam Malliappan; Premkumar, B; Prabhawathi, Veluchamy; Prabhakar, Pranav Kumar","year":2021,"journal":"Mini reviews in medicinal chemistry, 21(20), 3166-3182","doi":"10.2174/1389557521666210422114909","pmid":"33888049","tags":["glp-1-receptor-agonists","cardiovascular-effects","kidney-function"],"studyType":"review","evidenceStrength":"strong","keyFinding":"GLP-1 receptor agonists provide comprehensive benefits in type 2 diabetes: glycemic control, weight loss, cardiovascular event reduction, nephroprotection, neuroprotection, and potential retinal protection through pleiotropic mechanisms.","whyItMatters":"Diabetes complications are the main cause of disability and death in diabetic patients. Having one drug class that addresses blood sugar, weight, heart, kidneys, nerves, and eyes simplifies treatment and improves outcomes.","specificNumbers":"Reduce MACE; prevent macroalbuminuria; slow eGFR decline; neuroprotective; reduce stroke; improve retinal barrier; weight loss; anti-atherogenic; SGLT-2i combination improves renal outcomes","methodology":"Narrative review of GLP-1 receptor agonist literature covering mechanisms, dosing, monotherapy and combination therapy, and effects on diabetic complications across cardiovascular, renal, neurological, and retinal systems.","limitations":"Narrative review, not systematic. Covers many topics broadly without deep analysis of any single area. Some benefits (retinopathy, neuroprotection) have less robust clinical trial evidence than cardiovascular and renal effects."},{"rthcId":"RPEP-05771","title":"Role of fish collagen hydrolysate in attenuating inflammation-An in vitro study.","authors":"Sivaraman, K; Shanthi, C","year":2021,"journal":"Journal of food biochemistry, 45(9), e13876","doi":"10.1111/jfbc.13876","pmid":"34309035","tags":["collagen-peptides","inflammation","bioavailability"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"After two-step chromatographic purification, collagen hydrolysate fractions from Clarias batrachus (C2) and Pangasius pangasius (P2) fish skin showed potent anti-inflammatory activity in LPS-activated RAW 264.7 macrophage cells. The active peptides were in the 1–3 kDa molecular weight range.\n\nThe C2 fraction reduced TNF-α gene expression to a 1.6-fold difference and IL-6 expression to a 30-fold difference compared to LPS stimulation alone. The P2 fraction reduced TNF-α to a 1.0-fold difference (essentially to baseline) and IL-6 to a 40-fold difference.\n\nBoth fractions also suppressed inflammatory proteins including TNF-α, IL-6, NFκB, and phosphorylated IκB (p-IκB), confirming the anti-inflammatory activity operates through the NFκB signaling pathway.","whyItMatters":"Fish skin is a major byproduct of the seafood industry, mostly discarded as waste. Identifying potent anti-inflammatory peptides in this material creates a dual benefit: reducing waste while producing health-promoting compounds. As interest in food-derived bioactive peptides and natural anti-inflammatory agents grows, fish collagen hydrolysates represent an accessible and sustainable source.","specificNumbers":"5 fish species; 2 active fractions; 1-3 kDa peptides; TNF-α to 1.0-1.6 fold; IL-6 30-40 fold reduction; NFκB and p-IκB protein suppressed","methodology":"Collagen hydrolysates were prepared from the skin of five fish species. The hydrolysates underwent two-step chromatographic purification to isolate active fractions. Anti-inflammatory activity was tested in LPS-activated RAW 264.7 mouse macrophage cells by measuring gene expression (mRNA levels) and protein levels of inflammatory markers TNF-α, IL-6, NFκB, and p-IκB.","limitations":"This was an in vitro study using a mouse macrophage cell line (RAW 264.7), not human cells or a living organism. The specific peptide sequences responsible for the anti-inflammatory activity were not identified. No dosing, bioavailability, or absorption data were generated. The results need validation in animal models and eventually human studies before any health claims can be made."},{"rthcId":"RPEP-05772","title":"Signal Peptides - Promising Ingredients in Cosmetics.","authors":"Skibska, Agnieszka; Perlikowska, Renata","year":2021,"journal":"Current protein & peptide science, 22(10), 716-728","doi":"10.2174/1389203722666210812121129","pmid":"34382523","tags":["collagen-peptides","skin-health","peptide-engineering"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Signal peptides in cosmetics stimulate fibroblast collagen, elastin, fibronectin, and laminin production through signaling cascades, with expanding commercial applications due to improved synthesis methods.","whyItMatters":"The cosmetic peptide market is growing rapidly. Understanding which peptides work and how they work helps consumers and formulators make evidence-based choices in a market often driven by marketing claims.","specificNumbers":"4 peptide categories; signal peptides boost collagen, elastin, fibronectin, laminin; scalable synthesis; growing commercial market","methodology":"Literature review of signal peptides used in topical cosmetic applications, covering mechanisms of action, commercial products, and manufacturing advances.","limitations":"Review focuses on commercial cosmetic applications. Many cosmetic peptide claims lack rigorous clinical trial evidence. Skin penetration of topically applied peptides varies widely. Regulatory standards for cosmetic efficacy claims are less stringent than for drugs."},{"rthcId":"RPEP-05773","title":"Effects of carbohydrate restriction on postprandial glucose metabolism, β-cell function, gut hormone secretion, and satiety in patients with Type 2 diabetes.","authors":"Skytte, Mads J; Samkani, Amirsalar; Astrup, Arne; Frystyk, Jan; Rehfeld, Jens F; Holst, Jens J; Madsbad, Sten; Burling, Keith; Fenger, Mogens; Thomsen, Mads N; Larsen, Thomas M; Krarup, Thure; Haugaard, Steen B","year":2021,"journal":"American journal of physiology. Endocrinology and metabolism, 320(1), E7-E18","doi":"10.1152/ajpendo.00165.2020","pmid":"33103448","tags":["glp-1-receptor-agonists","insulin-regulation","appetite-regulation"],"studyType":"randomized-controlled-trial","evidenceStrength":"moderate","keyFinding":"CRHP diet reduced postprandial glucose AUC by 60%, improved beta cell sensitivity by 45%, lowered fasting proinsulin, increased GIP by 45%, and enhanced satiety in 28 T2D patients over 6 weeks.","whyItMatters":"Diet is the foundation of diabetes management. Showing that a specific macronutrient ratio improves beta cell function and satiety, not just blood sugar numbers, supports carb-reduced diets as therapeutic interventions.","specificNumbers":"28 patients; 6 weeks; post-meal glucose AUC -60%; Bup +45%; IGI +31%; fasting proinsulin reduced; GIP +45%; gastric emptying delayed 15 min; satiety increased; GLP-1 and PYY unchanged","methodology":"Randomized crossover study. 28 patients with type 2 diabetes (mean HbA1c 60 mmol/mol) ate CRHP (30/30/40) or CD (50/17/33) diet for 6 weeks each. Continuous glucose monitoring, mixed-meal tests, insulin secretion, proinsulin, gut hormones, gastric emptying, and satiety measured.","limitations":"Small crossover study with 28 patients. Only 6 weeks per diet. Long-term adherence and effects are unknown. The diets differed in multiple macronutrients, making it hard to attribute effects to any single change."},{"rthcId":"RPEP-05774","title":"Larazotide acetate: a pharmacological peptide approach to tight junction regulation.","authors":"Slifer, Zachary M; Krishnan, B Radha; Madan, Jay; Blikslager, Anthony T","year":2021,"journal":"American journal of physiology. Gastrointestinal and liver physiology, 320(6), G983-G989","doi":"10.1152/ajpgi.00386.2020","pmid":"33881350","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05775","title":"Advances in venom peptide drug discovery: where are we at and where are we heading?","authors":"Smallwood, Taylor B; Clark, Richard J","year":2021,"journal":"Expert opinion on drug discovery, 16(10), 1163-1173","doi":"10.1080/17460441.2021.1922386","pmid":"33914674","tags":["venom-derived-peptides","clinical-applications","drug-delivery-systems"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Multiple venom-derived peptide drugs are FDA-approved, and toxin-driven discovery approaches are expanding the clinical pipeline with candidates from previously unstudied venomous species.","whyItMatters":"Venoms are one of nature's richest sources of drug leads. With most venomous species still unexplored, the potential for new therapies is enormous. Advances in technology are making it practical to tap into this resource.","specificNumbers":"Multiple FDA-approved drugs; exenatide from Gila monster; ziconotide from cone snail; toxin-driven discovery expanding pipeline; applications in diabetes, pain, and more","methodology":"Expert review of FDA-approved venom-derived peptide drugs, peptides in preclinical and clinical development, drug development challenges, and emerging discovery technologies.","limitations":"Expert review, not systematic. Focus on peptides may underestimate non-peptide venom components. Drug development challenges (stability, delivery) remain significant hurdles for many candidates."},{"rthcId":"RPEP-05776","title":"Safety of Semaglutide.","authors":"Smits, Mark M; Van Raalte, Daniël H","year":2021,"journal":"Frontiers in endocrinology, 12, 645563","doi":"10.3389/fendo.2021.645563","pmid":"34305810","tags":["glp-1-receptor-agonists","clinical-applications","cardiovascular-effects"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Semaglutide's safety profile shows mainly transient GI side effects and increased cholelithiasis risk, with no unexpected safety signals across SUSTAIN and PIONEER trials and favorable cardiovascular outcomes.","whyItMatters":"Semaglutide is one of the most prescribed diabetes and weight loss drugs. A thorough safety review helps doctors and patients make informed decisions about long-term use.","specificNumbers":"GI effects: mild-moderate, transient; cholelithiasis increased; no proven pancreatic cancer; thyroid cancer inconclusive; rare hypoglycemia; DRP monitoring needed; CV outcomes beneficial","methodology":"Comprehensive review of phase 3 registration trials (SUSTAIN and PIONEER programs), cardiovascular outcome trials, and emerging real-world evidence for both subcutaneous and oral semaglutide.","limitations":"Review of trial data with limited long-term follow-up for rare events like cancer. Real-world data is still accumulating. Some safety concerns (thyroid, pancreas) cannot be fully resolved with current evidence due to low event rates."},{"rthcId":"RPEP-05777","title":"Comparison of the injection-site experience of the starting doses with semaglutide and dulaglutide: A randomized, double-blind trial in healthy subjects.","authors":"Snitker, Søren; Andersen, Andreas; Berg, Birgitte; van Marle, Sjoerd; Sparre, Thomas","year":2021,"journal":"Diabetes, obesity & metabolism, 23(6), 1415-1419","doi":"10.1111/dom.14349","pmid":"33591618","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05778","title":"Promising role of defensins peptides as therapeutics to combat against viral infection.","authors":"Solanki, Subhash Singh; Singh, Parul; Kashyap, Poonam; Sansi, Manish Singh; Ali, Syed Azmal","year":2021,"journal":"Microbial pathogenesis, 155, 104930","doi":"10.1016/j.micpath.2021.104930","pmid":"33933603","tags":["antimicrobial-peptides","immune-function","inflammation"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Defensin peptides have broad-spectrum antiviral activity through direct viral inactivation and immunomodulation, with potential as therapeutic adjuvants against viral infections including COVID-19.","whyItMatters":"Viral pandemics demand rapid therapeutic responses. Defensins, as natural immune components with broad antiviral activity, could supplement vaccines and antiviral drugs as adjuvant therapies.","specificNumbers":"α, β, θ defensin classes; broad-spectrum antiviral; immunomodulatory and immunoenhancing; potential anti-COVID-19 adjuvant; innate and adaptive immunity stimulation","methodology":"Review of literature on defensin peptide antiviral mechanisms, applications, and potential as anti-coronavirus therapeutic adjuvants.","limitations":"Review article. Most antiviral defensin data is in vitro. Clinical evidence for defensin-based antiviral therapy is limited. The COVID-19 application is theoretical and not yet tested in trials."},{"rthcId":"RPEP-05779","title":"Peptide Vaccination against Cytomegalovirus Induces Specific T Cell Response in Responses in CMV Seronegative End-Stage Renal Disease Patients.","authors":"Sommerer, Claudia; Schmitt, Anita; Hückelhoven-Krauss, Angela; Giese, Thomas; Bruckner, Thomas; Wang, Lei; Schnitzler, Paul; Meuer, Stefan; Zeier, Martin; Schmitt, Michael","year":2021,"journal":"Vaccines, 9(2)","doi":"10.3390/vaccines9020133","pmid":"33562163","tags":["peptide-vaccines","cytomegalovirus","transplant-medicine"],"studyType":"clinical-trial","evidenceStrength":"preliminary","keyFinding":"In a phase I clinical trial, a peptide vaccine based on a 9-amino acid fragment (NLVPMVATV) from CMV phosphoprotein 65 was given to 10 CMV-seronegative patients awaiting kidney transplantation. The vaccine was well tolerated with only mild local skin reactions. Five of 10 patients (50%) mounted an immune response, and 40% developed CMV-specific CD8+ T cells.\n\nThe most striking finding: none of the responders experienced CMV reactivation in the 18 months following transplantation, while all non-responders reactivated CMV. This 0% vs. 100% reactivation split, while from a tiny sample, is clinically compelling.","whyItMatters":"CMV reactivation after organ transplantation is a serious and potentially fatal complication, especially when a CMV-negative recipient receives an organ from a CMV-positive donor. Current prevention relies on antiviral drugs that have side effects and can't build lasting immunity. A peptide vaccine that generates protective T cell immunity before transplantation could fundamentally change how transplant centers manage this risk.","specificNumbers":"n=10 · 50% immune response rate · 40% CMV-specific CD8+ T cell response · 0% CMV reactivation in responders vs 100% in non-responders · 18 months follow-up · 4 biweekly subcutaneous injections · No serious adverse events","methodology":"Phase I clinical trial of 10 CMV-seronegative end-stage renal disease patients awaiting kidney transplantation. Patients received four biweekly subcutaneous injections of the CMVpp65 nonamer peptide NLVPMVATV in Montanide water-in-oil emulsion with imiquimod adjuvant. Immune responses were monitored using IFN-γ ELISpot assays and flow cytometry for CMV-specific CD8+ T cells over 18 months post-transplant.","limitations":"Extremely small sample size (10 patients) — the 0% vs 100% reactivation difference is compelling but could be coincidental. Phase I trial designed primarily for safety, not efficacy. Single-peptide approach targets only one CMV epitope. HLA restriction means the peptide may only work for patients with specific HLA types. No control group receiving placebo."},{"rthcId":"RPEP-05780","title":"The Role of Antimicrobial Peptides in Preterm Birth.","authors":"Son, Ga-Hyun; Lee, Jae-Jun; Kim, Youngmi; Lee, Keun-Young","year":2021,"journal":"International journal of molecular sciences, 22(16)","doi":"10.3390/ijms22168905","pmid":"34445608","tags":["antimicrobial-peptides","immune-function","clinical-applications"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Altered antimicrobial peptide expression is associated with preterm birth-related conditions including preterm labor, intra-amniotic infection, PPROM, and cervical insufficiency, suggesting AMPs as potential biomarkers or therapeutic targets.","whyItMatters":"Preterm birth is the leading cause of newborn death worldwide. If antimicrobial peptides can predict or prevent preterm birth, it could save many lives and reduce long-term disability.","specificNumbers":"AMPs altered in preterm labor, intra-amniotic infection/inflammation, PPROM, cervical insufficiency; AMP dysregulation affects pregnancy prognosis; potential biomarkers and therapeutic targets","methodology":"Review of published literature on antimicrobial peptide expression in preterm birth and related clinical presentations.","limitations":"Review article. Most studies are observational and associative. Causation between AMP changes and preterm birth is not established. AMP measurement methods and study populations vary widely across studies."},{"rthcId":"RPEP-05781","title":"Substance P Mediates Estrogen Modulation Proinflammatory Cytokines Release in Intervertebral Disc.","authors":"Song, Xiao-Xing; Jin, Lin-Yu; Li, Xin-Feng; Luo, Yan; Yu, Bu-Wei","year":2021,"journal":"Inflammation, 44(2), 506-517","doi":"10.1007/s10753-020-01347-1","pmid":"32965648","tags":["neuropeptides","inflammation","pain-management"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Estrogen reduces disc inflammation through substance P/NK1R signaling. NK1R agonist treatment reversed estrogen's anti-inflammatory effects on TNF-α, IL-1β, and IL-6 in intervertebral discs of ovariectomized mice.","whyItMatters":"Understanding how estrogen protects discs through neuropeptide pathways could lead to new treatments for disc degeneration, especially in postmenopausal women who lose estrogen protection.","specificNumbers":"OVX increased SP, NK1R, TNF-α, IL-1β, IL-6 in discs; estrogen reversed all; NK1R agonist blocked estrogen effects; two anti-inflammatory pathways identified","methodology":"Animal study. Female C57BL/6 mice divided into 4 groups: sham, ovariectomy (OVX), OVX + estrogen (E2), OVX + E2 + NK1R agonist. Measured SP, NK1R, TNF-α, IL-1β, IL-6 by immunohistochemistry and qPCR in intervertebral discs.","limitations":"Animal study in mice. Mouse disc biology differs from human. Only female mice studied. Short-term study. The NK1R agonist is a pharmacological tool, not a clinical drug. Estrogen replacement therapy has its own risks in humans."},{"rthcId":"RPEP-05782","title":"Combined Treatment with Bone Marrow-Derived Mesenchymal Stem Cells and Exendin-4 Promotes Islet Regeneration in Streptozotocin-Induced Diabetic Rats.","authors":"Song, Xiaoyan; Sun, Xiaoya; Hao, Haojie; Han, Qingwang; Han, Weidong; Mu, Yiming","year":2021,"journal":"Stem cells and development, 30(9), 502-514","doi":"10.1089/scd.2020.0137","pmid":"33677993","tags":["glp-1-receptor-agonists","insulin-regulation","stem-cell-research"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Combined MSC and exendin-4 treatment produced beta cells with higher PDX-1, MafA, FoxO1, and GLP-1R expression and better glucose-stimulated insulin secretion than MSC alone in STZ-diabetic rats.","whyItMatters":"Regenerating functional beta cells is the holy grail of diabetes treatment. This study shows that GLP-1 analogs can enhance the quality of stem cell-derived beta cells, potentially making regenerative therapies more effective.","specificNumbers":"40 rats; 5 groups; MSC+Ex4 significantly higher PDX-1, MafA, FoxO1, GLP-1R; increased insulin secretion; more insulin+/glucagon+ cells; no proliferation/apoptosis difference","methodology":"Animal study. 40 male Sprague-Dawley rats in 5 groups (normal, DM, MSC, Ex4, MSC+Ex4). Assessed glucose tolerance, insulin secretion, immunofluorescence for insulin/glucagon/transcription factors, and proliferation/apoptosis markers.","limitations":"Animal study in chemically induced diabetes, which differs from human type 1 or type 2 diabetes. Short-term study. Stem cell therapy is not yet practical for routine diabetes treatment. The mechanism by which exendin-4 improves transcription factor expression needs clarification."},{"rthcId":"RPEP-05783","title":"Efficacy and safety of anti-calcitonin gene-related peptide monoclonal antibodies for treatment of chronic migraine: A systematic review and network meta-analysis.","authors":"Soni, Prashant; Chawla, Evanka","year":2021,"journal":"Clinical neurology and neurosurgery, 209, 106893","doi":"10.1016/j.clineuro.2021.106893","pmid":"34464833","tags":["neuropeptides","clinical-applications","pain-management"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"All anti-CGRP mAbs showed comparable efficacy and safety for chronic migraine, with fremanezumab 675+225+225 mg SC and eptinezumab IV numerically favored but no statistically significant differences between treatments.","whyItMatters":"Chronic migraine is debilitating and harder to treat than episodic migraine. Knowing that all CGRP antibodies work similarly helps doctors choose based on practical factors like cost, route, and patient preference rather than perceived efficacy differences.","specificNumbers":"7 RCTs; 5,164 patients; 10 regimens; fremanezumab 675+225+225 numerically best; no significant between-drug differences; comparable safety and immunogenicity","methodology":"Systematic review and Bayesian network meta-analysis. 7 RCTs, 5,164 chronic migraine patients. Compared 10 treatment regimens across erenumab, fremanezumab, galcanezumab, and eptinezumab. Minimum 12 weeks treatment.","limitations":"Bayesian network meta-analysis with wide credible intervals due to indirect comparisons. No head-to-head trials included. Only chronic migraine analyzed. Short-term prevention (12+ weeks) only."},{"rthcId":"RPEP-05784","title":"Quality of Life Related to Functional Disability in Migraine Patients: A Systematic Review and Network Meta-analysis.","authors":"Soni, Prashant; Chawla, Evanka","year":2021,"journal":"The Clinical journal of pain, 37(11), 845-851","doi":"10.1097/AJP.0000000000000972","pmid":"34419975","tags":["neuropeptides","clinical-applications","pain-management"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Fremanezumab showed the greatest improvement in MIDAS disability scores for both chronic and episodic migraine, slightly outperforming erenumab, galcanezumab, and lower fremanezumab doses in 7,095 patients.","whyItMatters":"Reducing disability, not just headache days, is what matters most to migraine patients. This analysis focuses on the functional impact that determines quality of life.","specificNumbers":"9 RCTs; 7,095 patients; 41 studies screened; fremanezumab 675+225+225 best for chronic; fremanezumab 225 QM best for episodic; MIDAS scores compared","methodology":"Systematic review and Bayesian network meta-analysis. 9 RCTs, 7,095 migraine patients. Compared anti-CGRP mAb regimens using change in MIDAS (Migraine Disability Assessment) scores. Minimum 12 weeks treatment.","limitations":"Network meta-analysis with indirect comparisons. MIDAS is a patient-reported outcome with inherent variability. Differences between drugs were small. Follow-up was 12+ weeks only."},{"rthcId":"RPEP-05785","title":"Peptide-functionalized liposomes as therapeutic and diagnostic tools for cancer treatment.","authors":"Sonju, Jafrin Jobayer; Dahal, Achyut; Singh, Sitanshu S; Jois, Seetharama D","year":2021,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 329, 624-644","doi":"10.1016/j.jconrel.2020.09.055","pmid":"33010333","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05786","title":"Methods for Intracellular Delivery of Quantum Dots.","authors":"Souza, Sueden O; Lira, Rafael B; Cunha, Cássia R A; Santos, Beate S; Fontes, Adriana; Pereira, Goreti","year":2021,"journal":"Topics in current chemistry (Cham), 379(1), 1","doi":"10.1007/s41061-020-00313-7","pmid":"33398442","tags":["drug-delivery-systems","peptide-engineering","bioavailability"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Cell-penetrating peptides, electroporation, microinjection, molecular coatings, and liposomes each offer distinct advantages and limitations for intracellular quantum dot delivery, with CPPs providing membrane penetration but risking endosomal trapping.","whyItMatters":"Quantum dots enable advanced cell imaging, but getting them inside cells without damage is critical. Understanding delivery options helps researchers design better imaging experiments.","specificNumbers":"5 methods compared: electroporation, microinjection, CPPs, molecular coatings, liposomes; CPPs risk endosomal trapping; each method has distinct trade-offs","methodology":"Review of physical and biochemical methods for intracellular quantum dot delivery, comparing efficiency, cell viability, and practical considerations.","limitations":"Review article. No direct comparison experiments between methods. Performance depends heavily on specific QD size, surface chemistry, and target cell type."},{"rthcId":"RPEP-05787","title":"Re-Analyzing Phase III Bremelanotide Trials for \"Hypoactive Sexual Desire Disorder\" in Women.","authors":"Spielmans, Glen I","year":2021,"journal":"Journal of sex research, 58(9), 1085-1105","doi":"10.1080/00224499.2021.1885601","pmid":"33678061","tags":["neuropeptides","clinical-applications","hormonal-regulation"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Bremelanotide re-analysis showed 72.7% of protocol outcomes unreported, adverse event dropout OR=11.98 (NNH: 6), and participants preferred placebo (OR=0.30, NNH: 4) based on trial completion and open-label enrollment.","whyItMatters":"Approved drugs should have clear evidence of meaningful benefit. This re-analysis raises serious concerns about the transparency and validity of the data supporting bremelanotide's approval for HSDD.","specificNumbers":"72.7% protocol outcomes unreported; 15 non-protocol secondary measures added; adverse dropout OR 11.98 (NNH 6); participant preference OR 0.30 favoring placebo (NNH 4)","methodology":"Meta-analysis of two phase III RCTs using FDA New Drug Application data. Re-analyzed efficacy and safety outcomes, compared to protocol-specified endpoints, and assessed participant preference through trial completion and open-label enrollment.","limitations":"Re-analysis based on publicly available FDA data, which may not include all trial details. The author's interpretation of participant preference (completing trial + enrolling in open-label) is one of several possible measures. The original authors may have additional context."},{"rthcId":"RPEP-05788","title":"Growth Hormone Releasing Hormone Reduces Circulating Markers of Immune Activation in Parallel with Effects on Hepatic Immune Pathways in Individuals with HIV-infection and Nonalcoholic Fatty Liver Disease.","authors":"Stanley, Takara L; Fourman, Lindsay T; Wong, Lai Ping; Sadreyev, Ruslan; Billingsley, James M; Feldpausch, Meghan N; Zheng, Isabel; Pan, Chelsea S; Boutin, Autumn; Lee, Hang; Corey, Kathleen E; Torriani, Martin; Kleiner, David E; Chung, Raymond T; Hadigan, Colleen M; Grinspoon, Steven K","year":2021,"journal":"Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 73(4), 621-630","doi":"10.1093/cid/ciab019","pmid":"33852720","tags":["growth-hormone-secretagogues","immune-function","metabolic-health"],"studyType":"randomized-controlled-trial","evidenceStrength":"strong","keyFinding":"Tesamorelin decreased 13 circulating immune markers (chemokines, cytokines, T-cell molecules) and downregulated hepatic immune activation pathways in a 12-month randomized trial of 61 HIV patients with NAFLD.","whyItMatters":"Chronic immune activation in HIV accelerates liver disease, heart disease, and aging. Finding that a GHRH analog can dampen this activation opens a new therapeutic approach beyond traditional antiretroviral therapy.","specificNumbers":"61 patients; 12 months; 92 biomarkers; 13 decreased (CCL3, CCL4, CCL13, IL8, IL-10, CSF-1, CD8A, CRTAM, GZMA, ADGRG1, ARG1, Gal-9, HGF); 0 increased; liver transcriptomics confirmed","methodology":"Double-blind, randomized trial. 61 people with HIV and NAFLD received tesamorelin or placebo for 12 months. 92 immune biomarkers measured by proteomics. Gene set enrichment analysis on serial liver biopsies.","limitations":"Small trial (61 patients). HIV population may not generalize to other groups. Proteomics approach measures many markers, increasing chance of false positives. Only NAFLD patients studied, not HIV patients without liver disease."},{"rthcId":"RPEP-05789","title":"Relationship of IGF-1 and IGF-Binding Proteins to Disease Severity and Glycemia in Nonalcoholic Fatty Liver Disease.","authors":"Stanley, Takara L; Fourman, Lindsay T; Zheng, Isabel; McClure, Colin M; Feldpausch, Meghan N; Torriani, Martin; Corey, Kathleen E; Chung, Raymond T; Lee, Hang; Kleiner, David E; Hadigan, Colleen M; Grinspoon, Steven K","year":2021,"journal":"The Journal of clinical endocrinology and metabolism, 106(2), e520-e533","doi":"10.1210/clinem/dgaa792","pmid":"33125080","tags":["growth-hormone-secretagogues","metabolic-health","insulin-regulation"],"studyType":"randomized-controlled-trial","evidenceStrength":"moderate","keyFinding":"Hepatic IGF-1 mRNA was significantly lower in individuals with more severe steatosis (fat accumulation) and higher NAFLD Activity Scores, and was inversely related to blood glucose parameters independent of circulating IGF-1 levels. This means the liver's own IGF-1 production — not just what's in the blood — matters for metabolic health.\n\nAmong the binding proteins, IGFBP2 and IGFBP4 were lower while IGFBP6 and IGFBP7 were higher with increasing steatosis. Notably, IGFBP7 increased with fibrosis severity, making it a potential marker for scarring. GHRH treatment increased circulating IGFBP-1 and IGFBP-3 while decreasing IGFBP-2 and IGFBP-6, demonstrating that the GH axis can modify these binding protein profiles.","whyItMatters":"NAFLD affects roughly a quarter of the global population and is a leading cause of liver disease, yet treatment options remain limited. This study reveals that the IGF system in the liver is not just a passive bystander but actively linked to disease progression. The finding that GHRH can modify binding protein profiles opens a potential therapeutic avenue — and the divergent roles of different IGFBPs suggest that targeted approaches, not blanket IGF manipulation, will be needed.","specificNumbers":"61 patients; 39 with liver RNA-Seq; IGF1 inversely associated with steatosis/NAS; IGFBP2/4 low in severe disease; IGFBP6/7 high; IGFBP7 increased with fibrosis; GHRH increased IGFBP-1/3, decreased IGFBP-2/6","methodology":"This was a secondary analysis of data from a randomized clinical trial of GHRH conducted at two US academic medical centers. The 61 participants were HIV-infected adults aged 18-70 with at least 5% liver fat. Of these, 39 had RNA-Seq data from liver biopsies, allowing researchers to measure actual gene expression of IGF-1 and binding proteins in liver tissue and correlate these with histopathology (steatosis, inflammation, fibrosis) and glucose metabolism measures.","limitations":"The associations are cross-sectional and cannot prove causation. The study population was HIV-infected, which may limit generalizability to the broader NAFLD population since HIV and antiretroviral therapy can independently affect metabolism. The liver biopsy subset was small (39 patients), and multiple statistical comparisons increase the risk of false positive findings. GHRH effects on circulating IGFBPs may not reflect hepatic changes."},{"rthcId":"RPEP-05790","title":"High protein diet leads to prediabetes remission and positive changes in incretins and cardiovascular risk factors.","authors":"Stentz, Frankie B; Mikhael, Andrew; Kineish, Omer; Christman, John; Sands, Chris","year":2021,"journal":"Nutrition, metabolism, and cardiovascular diseases : NMCD, 31(4), 1227-1237","doi":"10.1016/j.numecd.2020.11.027","pmid":"33549435","tags":["glp-1-receptor-agonists","appetite-regulation","metabolic-health"],"studyType":"randomized-controlled-trial","evidenceStrength":"moderate","keyFinding":"High protein diet achieved 100% prediabetes remission vs 33% on high carb diet, with significantly greater increases in GLP-1 and GIP AUC, greater ghrelin suppression, and improved BNP over 6 months.","whyItMatters":"Prediabetes affects hundreds of millions of people globally. Achieving 100% remission with diet alone, through a mechanism involving satiety and incretin hormones, could prevent millions of diabetes cases.","specificNumbers":"24 participants; 100% vs 33% prediabetes remission; GLP-1 AUC p=0.001; GIP AUC p=0.005; ghrelin AUC p=0.001-0.005; BNP p=0.001; similar weight loss between groups","methodology":"Randomized controlled trial. 24 obese adults with prediabetes. High protein (n=12) vs high carbohydrate (n=12) diet for 6 months with all food provided. OGTT and MTT measured GLP-1, GIP, ghrelin, BNP, insulin, glucose at baseline and 6 months.","limitations":"Very small study (24 participants). All food was provided, which is not practical long-term. Six months may not predict lasting remission. No long-term follow-up. The HP and HC diets differed in multiple ways, not just protein content."},{"rthcId":"RPEP-05791","title":"Beyond Just Peptide Antigens: The Complex World of Peptide-Based Cancer Vaccines.","authors":"Stephens, Alexander J; Burgess-Brown, Nicola A; Jiang, Shisong","year":2021,"journal":"Frontiers in immunology, 12, 696791","doi":"10.3389/fimmu.2021.696791","pmid":"34276688","tags":["cancer-research","immune-function","peptide-engineering"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Peptide-based cancer vaccines are highly specific and safe but have struggled to demonstrate clinical efficacy due to tumor heterogeneity, self-tolerance, and immune suppression. The field has responded by evolving vaccine design through multiple generations: from simple peptide derivatives to overlapping peptide libraries, conjugated peptides, targeted delivery systems, neoantigen-based personalized vaccines, and combination strategies with checkpoint inhibitors and other therapies.\n\nThe review emphasizes that effective peptide vaccines must address multiple challenges simultaneously — stimulating antigen-presenting cells, enhancing cross-presentation, breaking self-tolerance, and overcoming the immunosuppressive tumor microenvironment.","whyItMatters":"Despite decades of research, no peptide-based cancer vaccine has become a standard-of-care treatment. This review maps the design innovations that address each failure mode, providing a roadmap for the field. As personalized medicine and immunotherapy converge, understanding these design principles is critical for developing vaccines that can finally succeed in the clinic.","specificNumbers":"Evolution: simple peptides → overlapping regions → conjugates → delivery systems → neoantigen personalization → combination with checkpoint inhibitors","methodology":"This is a narrative review synthesizing published literature on peptide-based cancer vaccine design, immune mechanisms, personalization strategies, and clinical development. It covers the evolution from first-generation simple peptide vaccines through current personalized neoantigen approaches.","limitations":"As a review, this paper does not present new experimental data. Most of the advanced vaccine designs discussed are still in early-phase clinical trials. Personalized neoantigen vaccines remain expensive and time-consuming to manufacture, which limits their scalability. The review acknowledges that tumor immune evasion continues to be a formidable barrier even with improved designs."},{"rthcId":"RPEP-05792","title":"Membrane and nuclear initiated estrogenic regulation of homeostasis.","authors":"Stincic, Todd L; Rønnekleiv, Oline K; Kelly, Martin J","year":2021,"journal":"Steroids, 168, 108428","doi":"10.1016/j.steroids.2019.108428","pmid":"31229508","tags":["neuropeptides","hormonal-regulation","appetite-regulation"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Estrogen coordinates kisspeptin, POMC, and AgRP neurons through dual membrane-initiated and nuclear signaling cascades, linking reproductive control with energy homeostasis in the hypothalamus.","whyItMatters":"Understanding how the brain links fertility to energy balance explains why conditions like obesity and anorexia disrupt reproduction. It also identifies therapeutic targets for both fertility and metabolic disorders.","specificNumbers":"3 neuron types from common progenitors; kisspeptin most estrogen-sensitive; both rapid membrane and nuclear signaling; coordinates fertility with metabolic status","methodology":"Review of recent research on estrogen regulation of hypothalamic arcuate nucleus neurons, covering synaptic interactions, membrane signaling, and intracellular cascades in kisspeptin, POMC, and AgRP neurons.","limitations":"Review based primarily on animal studies. Human hypothalamic neurobiology may differ. The complexity of interactions makes it difficult to predict therapeutic effects of targeting individual pathways."},{"rthcId":"RPEP-05793","title":"Characterizing Native and Hydrocarbon-Stapled Enfuvirtide Conformations with Ion Mobility Mass Spectrometry and Hydrogen-Deuterium Exchange.","authors":"Stocks, Bradley B; Bird, Gregory H; Walensky, Loren D; Melanson, Jeremy E","year":2021,"journal":"Journal of the American Society for Mass Spectrometry, 32(3), 753-761","doi":"10.1021/jasms.0c00453","pmid":"33534566","tags":["peptide-engineering","drug-delivery-systems","clinical-applications"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"IM-MS and HDX-MS detected discrete conformational states of enfuvirtide that correlate with α-helical content, with staple location dramatically altering the conformational ensemble populated by the peptide.","whyItMatters":"Stapled peptides are a growing drug class, but optimizing staple placement is slow. Fast MS-based methods that reveal which shapes a peptide adopts could dramatically speed up the development of new stapled peptide therapeutics.","specificNumbers":"36-residue enfuvirtide; multiple IM-MS conformations detected; HDX-MS correlated with CD helical content; staple location determines conformational ensemble","methodology":"Biophysical study comparing native 36-residue enfuvirtide with hydrocarbon-stapled variants. Used ion mobility mass spectrometry (IM-MS) and hydrogen-deuterium exchange mass spectrometry (HDX-MS). Compared results to circular dichroism measurements.","limitations":"Tested on one peptide (enfuvirtide). Gas-phase conformations (IM-MS) may not perfectly represent solution behavior. The correlation with biological activity was not tested directly."},{"rthcId":"RPEP-05794","title":"Brain Protein Expression Profile Confirms the Protective Effect of the ACTH(4-7)PGP Peptide (Semax) in a Rat Model of Cerebral Ischemia-Reperfusion.","authors":"Sudarkina, Olga Yu; Filippenkov, Ivan B; Stavchansky, Vasily V; Denisova, Alina E; Yuzhakov, Vadim V; Sevan'kaeva, Larisa E; Valieva, Liya V; Remizova, Julia A; Dmitrieva, Veronika G; Gubsky, Leonid V; Myasoedov, Nikolai F; Limborska, Svetlana A; Dergunova, Lyudmila V","year":2021,"journal":"International journal of molecular sciences, 22(12)","doi":"10.3390/ijms22126179","pmid":"34201112","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"At 24 hours after transient middle cerebral artery occlusion (tMCAO) in rats, Semax treatment produced measurable changes in four key brain proteins:\n\n- **CREB** (recovery/neuroprotection): Upregulated in subcortical structures, including the ischemic damage focus\n- **MMP-9** (inflammation/tissue breakdown): Downregulated in the adjacent frontoparietal cortex\n- **c-Fos** (inflammatory signaling): Downregulated in the frontoparietal cortex\n- **JNK** (cell death pathway): Downregulated in both subcortical structures and cortex\n\nThese protein-level changes are consistent with previous transcriptome data showing Semax suppresses inflammatory gene expression and activates neurotransmitter genes after ischemic injury.","whyItMatters":"Semax is one of the few peptide drugs actually approved for stroke treatment (in Russia), but the molecular mechanisms behind its protective effects have not been fully understood. This study provides protein-level confirmation that Semax works through a dual mechanism: suppressing inflammation and cell death while activating recovery pathways. Understanding these mechanisms could help optimize Semax dosing and potentially guide the development of similar neuroprotective peptides for broader clinical use.","specificNumbers":"","methodology":"Researchers used the rat transient middle cerebral artery occlusion (tMCAO) model to simulate ischemic stroke. Semax was administered, and brain tissue was collected at 24 hours post-stroke. Expression profiling of four key proteins — MMP-9, c-Fos, JNK, and CREB — was performed in subcortical structures (including the ischemic core) and the adjacent frontoparietal cortex. Results were integrated with previous genome-wide RNA-Seq data to construct a regulatory network linking transcriptomic and proteomic changes.","limitations":"This is a preclinical study in rats, and results may not directly translate to humans. Only four proteins were profiled in detail, representing a small fraction of the molecular changes occurring after stroke. The tMCAO model, while widely used, does not perfectly replicate all aspects of human ischemic stroke. The study examined a single time point (24 hours), so the temporal dynamics of Semax's effects are not captured."},{"rthcId":"RPEP-05795","title":"The role of the corticotropin-releasing hormone and its receptors in the regulation of stress response.","authors":"Sukhareva, E V","year":2021,"journal":"Vavilovskii zhurnal genetiki i selektsii, 25(2), 216-223","doi":"10.18699/VJ21.025","pmid":"34901719","tags":["neuropeptides","mental-health","hormonal-regulation"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"CRH coordinates stress responses through CRHR1/CRHR2 in hypothalamic and extrahypothalamic brain regions, with dysregulation linked to depression, anxiety, addiction, and neurodegeneration, making CRHR1 a therapeutic target.","whyItMatters":"Stress-related mental health disorders affect billions of people. Understanding the CRH system provides targets for new treatments that address the root biology of these conditions rather than just symptoms.","specificNumbers":"2 receptors (CRHR1, CRHR2); HPA axis + extrahypothalamic pathways; linked to depression, anxiety, addiction, Alzheimer's; CRHR1 antagonists as potential antidepressants; CRH regulates brain structure","methodology":"Narrative review of CRH system biology, receptor pharmacology, stress pathway mechanisms, and involvement in psychiatric and neurodegenerative disorders.","limitations":"Review based on animal and human studies of varying quality. CRHR1 antagonists have not yet proven effective in clinical trials. The complexity of the CRH system makes targeted intervention challenging."},{"rthcId":"RPEP-05796","title":"RD43 rice flour: the effect on starch digestibility and quality of noodles, glycemic response, short-acting satiety hormones and appetite control in humans.","authors":"Suklaew, Phim On; Chusak, Charoonsri; Wang, Chin-Kun; Adisakwattana, Sirichai","year":2021,"journal":"Food & function, 12(17), 7975-7985","doi":"10.1039/d1fo01389k","pmid":"34259302","tags":["glp-1-receptor-agonists","appetite-regulation","metabolic-health"],"studyType":"randomized-controlled-trial","evidenceStrength":"moderate","keyFinding":"Noodles prepared with 30% RD43 rice flour substitution significantly lowered postprandial plasma glucose at 15–90 minutes compared to control noodles. At the same time, the modified noodles significantly increased circulating levels of two key satiety peptide hormones — GLP-1 (glucagon-like peptide-1) and PYY (peptide tyrosine-tyrosine) — at 30 minutes after consumption.\n\nParticipants also reported significantly lower desire to eat and higher fullness lasting up to 120 minutes after consuming the RD43 rice noodles. The food science analysis showed that increasing RD43 rice flour content from 10–40% progressively reduced starch digestibility and rapidly digestible starch while increasing undigestible starch. Importantly, the 30% substitution level maintained similar overall sensory acceptability to conventional noodles.","whyItMatters":"Finding ways to naturally stimulate the body's own satiety hormones through everyday foods — rather than injectable drugs — could offer a practical, population-level approach to managing blood sugar and controlling appetite. This is especially relevant given the growing interest in GLP-1 as a therapeutic target for diabetes and obesity.","specificNumbers":"30% RD43 rice flour; GLP-1 and PYY increased at 30 min; glucose lower at 15-90 min; desire to eat decreased and fullness increased until 120 min; similar overall acceptability","methodology":"This was a combined food science and human crossover study. Researchers first developed noodles with 10–40% RD43 rice flour substitution and characterized their starch digestibility, physicochemical properties, and sensory attributes. They then conducted a human meal test comparing 30% RD43 rice noodles against control noodles, measuring postprandial blood glucose, GLP-1, PYY, and subjective appetite ratings over time.","limitations":"The sample size for the human study was not specified in the abstract, so the statistical power is unclear. This was an acute single-meal test, not a long-term dietary intervention, so it's unknown whether the effects persist with regular consumption. Only one rice variety (RD43) was tested, and cultural food preferences may limit how widely rice flour noodles could be adopted outside Asian populations."},{"rthcId":"RPEP-05797","title":"Neoantigen Dendritic Cell Vaccination Combined with Anti-CD38 and CpG Elicits Anti-Tumor Immunity against the Immune Checkpoint Therapy-Resistant Murine Lung Cancer Cell Line LLC1.","authors":"Sun, Changbo; Nagaoka, Koji; Kobayashi, Yukari; Nakagawa, Hidewaki; Kakimi, Kazuhiro; Nakajima, Jun","year":2021,"journal":"Cancers, 13(21)","doi":"10.3390/cancers13215508","pmid":"34771674","tags":["cancer-research","immune-function","peptide-engineering"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"From 2,536 missense mutations in the LLC1 lung cancer cell line, researchers identified 132 candidate neoantigen peptides, of which 25 induced CD8+ T cell responses. Short peptides failed to inhibit tumor growth as vaccines, but long peptide (L82)-pulsed dendritic cells delayed tumor growth in vivo. Combining L82-pulsed DC vaccination with anti-CD38 antibody effectively suppressed tumor growth by decreasing regulatory T cells in the tumor microenvironment, converting an immunotherapy-resistant cold tumor into one susceptible to immune rejection.","whyItMatters":"Roughly half of cancer patients don't respond to immunotherapy because their tumors are immunologically 'cold.' Finding ways to convert cold tumors into hot ones is one of the biggest challenges in oncology. This study demonstrates that a personalized neoantigen peptide vaccine combined with targeted antibody therapy can achieve this conversion, offering a potential strategy for treatment-resistant cancers.","specificNumbers":"2,536 mutations; 132 candidate peptides; 25 CD8+ reactive; L82 long peptide delayed growth; anti-CD38 combo suppressed tumors; regulatory T cells decreased","methodology":"Whole-exome and RNA sequencing of the LLC1 cell line identified neoantigen candidates. 132 short peptides were screened for immunogenicity, and 25 induced CD8+ T cell responses. Dendritic cells were pulsed with long peptides and tested as vaccines in mice bearing LLC1 tumors. RNA-Seq identified high CD38 expression on tumor cells, leading to combination treatment with anti-CD38 antibody. Tumor growth, T cell responses, and tumor-infiltrating lymphocyte composition were assessed.","limitations":"This is a mouse study using a single lung cancer cell line (LLC1), limiting generalizability. Only one of the tested long peptides (L82) was effective as a vaccine. The approach requires tumor sequencing, neoantigen prediction, and combination therapy, making clinical implementation complex and expensive. Sample sizes for the animal experiments were not specified in the abstract."},{"rthcId":"RPEP-05798","title":"PDGFRβ Recognizes and Binds Bacteria to Activate Src/Stat Pathway in Oysters.","authors":"Sun, Jiejie; Wu, Zhaojun; Wu, Wei; Leng, Jinyuan; Lv, Xiaoqian; Zhang, Tong; Wang, Lingling; Song, Linsheng","year":2021,"journal":"Journal of immunology (Baltimore, Md. : 1950), 207(12), 3060-3069","doi":"10.4049/jimmunol.2100486","pmid":"34799429","tags":["antimicrobial-peptides","immune-function","receptor-biology"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Oyster CgPDGFRβ recognizes Gram-negative bacteria, forms dimers, activates Src/Stat signaling, and induces Big defensin 1, IL17-4, and TNF1 expression in hemocytes.","whyItMatters":"Understanding how invertebrate immune systems recognize bacteria and produce antimicrobial peptides reveals ancient defense mechanisms that may inform both aquaculture health management and fundamental immunology.","specificNumbers":"CgPDGFRβ: 3 Ig domains + kinase; higher Gram-negative/LPS binding; dimerization; CgSrc Tyr416 phosphorylation; CgStat nuclear translocation; CgBigdef1, CgIL17-4, CgTNF1 induced","methodology":"Lab study in Pacific oyster (Crassostrea gigas). Identified CgPDGFRβ receptor. Tested binding to Gram-negative/positive bacteria and their components. Tracked receptor dimerization, Src phosphorylation, Stat nuclear translocation, and downstream gene expression.","limitations":"Study in an invertebrate (oyster). Direct translation to vertebrate immunity is limited. Only one receptor and signaling pathway studied. In vivo functional significance in disease resistance not tested."},{"rthcId":"RPEP-05799","title":"Circular RNA PIP5K1A (circPIP5K1A) accelerates endometriosis progression by regulating the miR-153-3p/Thymosin Beta-4 X-Linked (TMSB4X) pathway.","authors":"Sun, Lin; Wei, Yan; Wang, Junli","year":2021,"journal":"Bioengineered, 12(1), 7104-7118","doi":"10.1080/21655979.2021.1978618","pmid":"34546850","tags":["thymosin-beta-4","inflammation","hormonal-regulation"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"CircPIP5K1A was significantly elevated in endometriosis tissues and cells. Silencing circPIP5K1A suppressed proliferation, blocked cell cycle progression, increased apoptosis, and decreased migration and invasion. The mechanism: circPIP5K1A sponges miR-153-3p, relieving its suppression of TMSB4X (Thymosin beta-4 X-linked). Elevated TMSB4X then activates TGF-β signaling, promoting endometriosis progression. Inhibiting miR-153-3p reversed the effects of circPIP5K1A knockdown, confirming the regulatory axis.","whyItMatters":"Endometriosis affects about 190 million women worldwide and has limited treatment options beyond hormones and surgery. Identifying Thymosin beta-4 as a key driver — regulated through a specific circRNA-miRNA axis — reveals a potential new therapeutic target. If this pathway can be blocked, it could offer a novel, non-hormonal treatment approach.","specificNumbers":"CircPIP5K1A high in EM; silencing reduced proliferation, migration, invasion; increased apoptosis; miR-153-3p sponging confirmed; TMSB4X upregulated; TGF-β pathway activated","methodology":"In vitro study using endometriosis tissues and hEM15A cells. Gene/protein expression measured by RT-qPCR and Western blotting. Functional assays: CCK-8 (viability), wound healing (migration), transwell (invasion), flow cytometry (cell cycle, apoptosis). Molecular interactions confirmed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP).","limitations":"Entirely in vitro — no animal model or clinical validation of the circPIP5K1A/miR-153-3p/TMSB4X axis in vivo. Endometriosis involves complex hormonal, immune, and stromal interactions not captured in cell culture. The therapeutic potential of targeting this pathway remains speculative. The study used a single endometriosis cell line, limiting generalizability across endometriosis subtypes."},{"rthcId":"RPEP-05800","title":"AngIV-Analog Dihexa Rescues Cognitive Impairment and Recovers Memory in the APP/PS1 Mouse via the PI3K/AKT Signaling Pathway.","authors":"Sun, Xiaojin; Deng, Yang; Fu, Xinxin; Wang, Siyu; Duan, Rui; Zhang, Yingdong","year":2021,"journal":"Brain sciences, 11(11)","doi":"10.3390/brainsci11111487","pmid":"34827486","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05801","title":"Decrease of α-defensin impairs intestinal metabolite homeostasis via dysbiosis in mouse chronic social defeat stress model.","authors":"Suzuki, Kosuke; Nakamura, Kiminori; Shimizu, Yu; Yokoi, Yuki; Ohira, Shuya; Hagiwara, Mizu; Wang, Yi; Song, Yuchi; Aizawa, Tomoyasu; Ayabe, Tokiyoshi","year":2021,"journal":"Scientific reports, 11(1), 9915","doi":"10.1038/s41598-021-89308-y","pmid":"33972646","tags":["antimicrobial-peptides","gut-health","mental-health"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Chronic social defeat stress reduced Paneth cell alpha-defensin secretion, causing dysbiosis and metabolite changes that were reversed by alpha-defensin administration in mice.","whyItMatters":"The gut-brain connection in depression is increasingly recognized but poorly understood. This study identifies alpha-defensin as a key link between psychological stress, microbiome disruption, and potentially depression.","specificNumbers":"CSDS reduced α-defensin secretion; induced dysbiosis; changed metabolites; all reversed by α-defensin administration; Paneth cells identified as stress-responsive","methodology":"Mouse depression model (chronic social defeat stress). Measured Paneth cell alpha-defensin secretion. Analyzed intestinal microbiota composition and metabolites. Tested whether exogenous alpha-defensin administration could reverse stress-induced changes.","limitations":"Mouse model of depression, which has limitations in modeling human depression. Only one stress model tested. The specific microbiome and metabolite changes were not detailed in the abstract. Whether similar mechanisms operate in humans is unknown."},{"rthcId":"RPEP-05802","title":"Advances in peptide-mediated cytosolic delivery of proteins.","authors":"Sánchez-Navarro, Macarena","year":2021,"journal":"Advanced drug delivery reviews, 171, 187-198","doi":"10.1016/j.addr.2021.02.003","pmid":"33561452","tags":["drug-delivery-systems","peptide-engineering","bioavailability"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Cell-penetrating peptides enable cytosolic delivery of therapeutic proteins, with latest advances improving delivery efficiency and new assays confirming true intracellular distribution of protein cargo.","whyItMatters":"Most disease targets are inside cells, but most protein drugs cannot get there. CPPs that reliably deliver proteins to the cell interior could unlock treatments for many currently undruggable diseases.","specificNumbers":"Protein drugs growing exponentially; multiple CPP conjugation strategies; new in vitro assays for confirming cytosolic vs endosomal distribution","methodology":"Review article summarizing recent strategies for CPP-mediated protein delivery, including conjugation methods, delivery enhancement techniques, and in vitro assays for assessing intracellular protein distribution.","limitations":"Review article. Most studies covered are in vitro. Translating CPP-protein delivery to clinical use faces challenges including stability, immunogenicity, and manufacturing scale."},{"rthcId":"RPEP-05803","title":"The gastrointestinal tract in hunger and satiety signalling.","authors":"Tack, Jan; Verbeure, Wout; Mori, Hideki; Schol, Jolien; Van den Houte, Karen; Huang, I-Hsuan; Balsiger, Lukas; Broeders, Bert; Colomier, Esther; Scarpellini, Emidio; Carbone, Florencia","year":2021,"journal":"United European gastroenterology journal, 9(6), 727-734","doi":"10.1002/ueg2.12097","pmid":"34153172","tags":["appetite-regulation","glp-1-receptor-agonists","gut-health"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Gastric accommodation is the major determinant of meal volume, motilin drives return of hunger, and GLP-1/CCK/ghrelin/PYY provide hormonal gut-brain signaling for hunger and satiety regulation.","whyItMatters":"Understanding the gut signals that control eating is fundamental to treating obesity and eating disorders. These are the same pathways targeted by GLP-1 drugs and other appetite medications.","specificNumbers":"Gastric accommodation: major meal volume determinant; motilin: hunger return via phase 3; GLP-1, CCK, PYY: satiety; ghrelin: hunger; bitter tastants and GLP-1 analogs modulate pathways","methodology":"Narrative review of gastrointestinal mechanisms involved in hunger and satiety signaling, covering mechano/chemoreceptors, peptide hormones, and neural pathways.","limitations":"Narrative review. Some mechanisms are better studied than others. Motilin's role in hunger is well-supported but less studied therapeutically. Individual variation in these pathways is not addressed."},{"rthcId":"RPEP-05804","title":"Thymosin β4 increases cardiac cell proliferation, cell engraftment, and the reparative potency of human induced-pluripotent stem cell-derived cardiomyocytes in a porcine model of acute myocardial infarction.","authors":"Tan, Shi Hua; Loo, Sze Jie; Gao, Yu; Tao, Zhong Hao; Su, Li Ping; Wang, Chen Xu; Zhang, Sophia L; Mu, Yong Hui; Cui, Ying Hua; Abdurrachim, Desiree; Wang, Wei Hsin; Lalic, Janise; Lim, Kheng Choon; Bu, Jun; Tan, Ru San; Lee, Teck Hock; Zhang, Jianyi; Ye, Lei","year":2021,"journal":"Theranostics, 11(16), 7879-7895","doi":"10.7150/thno.56757","pmid":"34335970","tags":["thymosin-beta-4","heart-health","stem-cell-research"],"studyType":"animal-study","evidenceStrength":"strong","keyFinding":"Co-treatment with Tb4 microspheres and hiPSC-CMs significantly enhanced cell engraftment, vasculogenesis, cardiomyocyte proliferation, left ventricular function, and reduced infarct size in pigs after MI, with no arrhythmia or tumorigenesis.","whyItMatters":"Heart attacks damage heart muscle irreversibly. Stem cell therapy has been disappointing due to poor cell survival. Tb4 could be the missing ingredient that makes cardiac stem cell therapy actually work.","specificNumbers":"1.2×10⁸ hiPSC-CMs; 600 ng/mL Tb4; 2-week sustained release; improved LV function; reduced infarct size; enhanced engraftment and vasculogenesis; no arrhythmias; no tumors; AKT and BcL-XL upregulated","methodology":"Randomized pig study. MI induced, then 4 groups: basal medium, Tb4 microspheres, hiPSC-CMs (1.2×10⁸), or both. Tb4 delivered via gelatin microspheres (sustained release ~2 weeks). Assessed by cardiac MRI, implanted loop recorders, and whole-body MRI for tumors.","limitations":"Pig model, not humans. Relatively short follow-up. Immunosuppression was required for human-derived cells. The 1.2×10⁸ cell dose may not be directly translatable. Manufacturing complexity of both Tb4 microspheres and hiPSC-CMs is significant."},{"rthcId":"RPEP-05805","title":"The Role of Neuropeptide Y in the Nucleus Accumbens.","authors":"Tanaka, Masaki; Yamada, Shunji; Watanabe, Yoshihisa","year":2021,"journal":"International journal of molecular sciences, 22(14)","doi":"10.3390/ijms22147287","pmid":"34298907","tags":["neuropeptide-y","brain-and-cognition","addiction-and-reward"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"NPY in the nucleus accumbens controls alcohol intake, drug addiction, fat consumption, and emotional behavior through dopamine regulation.","whyItMatters":"Understanding how NPY works in the brain's reward center could lead to new treatments for addiction, overeating, and mood disorders.","specificNumbers":"Y1, Y2, and Y5 receptor subtypes; nucleus accumbens among highest NPY brain concentrations","methodology":"Literature review of animal studies on NPY expression and function in the nucleus accumbens.","limitations":"This is a review, not new research. Most findings come from animal studies. Results may not directly apply to humans."},{"rthcId":"RPEP-05806","title":"Direct protein delivery into intact plant cells using polyhistidine peptides.","authors":"Tanaka, Yoshino; Nanasato, Yoshihiko; Omura, Kousei; Endoh, Keita; Kawano, Tsuyoshi; Iwasaki, Takashi","year":2021,"journal":"Bioscience, biotechnology, and biochemistry, 85(6), 1405-1414","doi":"10.1093/bbb/zbab055","pmid":"33791772","tags":["peptide-drug-delivery","cell-penetrating-peptides","bioavailability-and-absorption"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Polyhistidine peptides with 20 residues (His20) most effectively delivered functional proteins into multiple plant cell types.","whyItMatters":"This gives scientists a new tool to deliver proteins into plant cells, which could help in crop research and biotechnology.","specificNumbers":"His8 to His20 tested; 3 plant species; His20 showed maximum fluorescence","methodology":"Lab study testing fusion proteins with varying histidine lengths in three plant cell lines. Used fluorescence and cAMP production to confirm delivery.","limitations":"Only tested in cultured plant cells, not whole plants. Long-term effects of protein delivery were not studied."},{"rthcId":"RPEP-05807","title":"Benefits of Sustained Upregulated Unimolecular GLP-1 and CCK Receptor Signalling in Obesity-Diabetes.","authors":"Tanday, Neil; English, Andrew; Lafferty, Ryan A; Flatt, Peter R; Irwin, Nigel","year":2021,"journal":"Frontiers in endocrinology, 12, 674704","doi":"10.3389/fendo.2021.674704","pmid":"34054734","tags":["glp-1","diabetes-and-metabolism","weight-management"],"studyType":"animal","evidenceStrength":"preliminary","keyFinding":"The hybrid peptide [Lys12Pal]Ex-4/CCK demonstrated prominent insulin-releasing (insulinotropic) actions in laboratory cell tests. When administered to diabetic high-fat-fed mice with chemically damaged pancreatic beta cells for 28 days, the dual-acting peptide produced significant reductions in blood glucose levels and body weight compared to controls.\n\nImportantly, beta-cell function markers also improved, suggesting the peptide didn't just lower blood sugar temporarily but helped protect or restore the insulin-producing cells themselves. Both exendin-4 (a GLP-1 agonist) and CCK individually showed beneficial effects on beta cells, but the combined approach in a single molecule aimed to capture synergistic benefits of activating both pathways simultaneously.","whyItMatters":"Current GLP-1 drugs are already revolutionary for diabetes and obesity treatment, but they only target one pathway. CCK is another powerful satiety hormone that works through different mechanisms. Combining both signals in a single molecule could provide stronger appetite suppression, better blood sugar control, and more robust beta-cell protection than GLP-1 alone — potentially representing the next evolution beyond today's single- and dual-agonist drugs.","specificNumbers":"28-day treatment; dual GLP-1/CCK1 receptor activation; significant reductions in blood glucose and body weight","methodology":"The study first established the individual and combined effects of GLP-1 and CCK1 receptor activation on pancreatic beta cells in vitro. Researchers then characterized the bioactivity of an acylated (lipid-modified for longer action) dual-acting GLP-1/CCK hybrid peptide called [Lys12Pal]Ex-4/CCK. For the in vivo study, male C57BL mice were placed on a high-fat diet and given streptozotocin (STZ) to damage their beta cells, creating a model of obesity-related type 2 diabetes. Mice were treated with the hybrid peptide for 28 days, with measurements of blood glucose, body weight, insulin secretion, and beta-cell function markers.","limitations":"This was an animal study in mice with chemically induced diabetes, which doesn't perfectly replicate human type 2 diabetes. The abstract contains formatting artifacts that obscure some specific statistical values. The hybrid peptide has not been tested in humans. The 28-day treatment period is relatively short for assessing long-term efficacy and safety. High-fat-diet/STZ mouse models, while useful, may overestimate treatment effects compared to the slower progression of human disease."},{"rthcId":"RPEP-05808","title":"Rational Design of a Dual-Targeting Natural Toxin-Like Bicyclic Peptide for Selective Bioenergetic Blockage in Cancer Cells.","authors":"Tang, Rui; Song, Yue; Shi, Mengzhen; Jiang, Zherui; Zhang, Ling; Xiao, Yao; Tian, Yuan; Zhou, Shaobing","year":2021,"journal":"Bioconjugate chemistry, 32(10), 2173-2183","doi":"10.1021/acs.bioconjchem.1c00366","pmid":"34606715","tags":["peptide-drug-delivery","cancer-and-oncology-peptides","cell-penetrating-peptides"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Dual-targeting bicyclic peptides selectively killed integrin-positive cancer cells by disrupting mitochondrial function while sparing normal cells.","whyItMatters":"Selective cancer-killing peptides could reduce side effects compared to traditional chemotherapy that damages healthy cells too.","specificNumbers":"i, i+7 thioether cross-link; stable under denaturants and high temperature; selective killing of integrin-positive cells","methodology":"Lab study. Designed and synthesized bicyclic peptides using thiol-yne chemistry. Tested cell killing in integrin-positive B16F10 melanoma cells versus normal cells.","limitations":"Only tested in cell culture, not in animals or humans. Only one cancer cell type was used. Real tumors are more complex than lab-grown cells."},{"rthcId":"RPEP-05809","title":"Novel scorpion venom peptide HsTx2 ameliorates cerebral ischemic brain injury in rats via the MAPK signaling pathway.","authors":"Tao, Jian; Yin, Saige; Song, Yongli; Zeng, Lin; Li, Shanshan; Liu, Naixin; Sun, Huiling; Fu, Zhe; Wang, Yinglei; Li, Yilin; Liu, Yixiang; Sun, Jun; Wang, Ying; Yang, Xinwang","year":2021,"journal":"Biochemical and biophysical research communications, 534, 442-449","doi":"10.1016/j.bbrc.2020.11.062","pmid":"33248693","tags":["venom-derived-peptides","brain-and-cognition","neuroprotection"],"studyType":"animal","evidenceStrength":"preliminary","keyFinding":"Scorpion venom peptide HsTx2 reduced stroke damage in rats by activating protective MAPK signaling while suppressing harmful inflammation in microglia.","whyItMatters":"Stroke treatments are limited. Finding new neuroprotective compounds from natural sources like venom could lead to better therapies.","specificNumbers":"25 amino acids; 2,861.855 Da; up-regulated p-ERK1/2 in cortex and microglia; reduced infarct area","methodology":"Animal study. Induced ischemic stroke in rats, then treated with HsTx2. Measured infarct area, behavior, and MAPK pathway proteins in brain tissue and microglia.","limitations":"This is an animal study in rats. The peptide has not been tested in humans. Stroke models in rats do not perfectly mimic human strokes."},{"rthcId":"RPEP-05810","title":"The neuroprotection of cerebrolysin after spontaneous intracerebral hemorrhage through regulates necroptosis via Akt/ GSK3β signaling pathway.","authors":"Tao, Yunna; Xu, Yeping; Shen, Meng; Feng, Xiaoyan; Wu, Yan; Wu, Youping; Shen, Liuyan; Wang, Yuhai","year":2021,"journal":"Acta cirurgica brasileira, 36(10), e361002","doi":"10.1590/ACB361002","pmid":"34817023","tags":["neuroprotection","cerebrolysin","brain-injury"],"studyType":"Animal Study","evidenceStrength":"Preliminary","keyFinding":"Cerebrolysin (CBL) treatment significantly improved outcomes after intracerebral hemorrhage (brain bleeding) in mice. Treated mice showed increased survival rates, better neurological scores, and greater neuron survival compared to untreated controls.\n\nThe protective mechanism involved inhibition of necroptosis — a form of programmed cell death. Cerebrolysin reduced the expression of RIP1 and RIP3 proteins, which are key drivers of necroptosis, through activation of the Akt/GSK3β signaling pathway. This suggests cerebrolysin protects brain cells not just by supporting their growth, but by actively blocking the cell death pathway that kills neurons after a brain hemorrhage.","whyItMatters":"Intracerebral hemorrhage (bleeding within the brain) is one of the deadliest types of stroke, with limited treatment options. Much of the brain damage occurs not from the initial bleed but from secondary injury — inflammation and cell death cascading outward from the hemorrhage site. This study shows that cerebrolysin, a peptide mixture already used clinically as a neurotrophic agent, can reduce this secondary damage by blocking necroptosis. Identifying the specific molecular pathway (Akt/GSK3β) provides a mechanistic basis for potential clinical trials.","specificNumbers":"C57BL/6 mouse model · increased survival rate · improved neurological scores · reduced RIP1/RIP3 expression · Akt/GSK3β pathway","methodology":"Researchers induced intracerebral hemorrhage in C57BL/6 mice and treated them with cerebrolysin. They assessed outcomes using mortality rates, neurological scoring, brain water content (edema), and TUNEL staining (to detect dying cells). Evans blue extravasation measured blood-brain barrier damage. Western blotting and quantitative PCR analyzed the expression of necroptosis markers (RIP1, RIP3) and Akt/GSK3β pathway components.","limitations":"This is a mouse study, and results may not translate directly to human intracerebral hemorrhage. The abstract does not provide specific group sizes or dose details. Cerebrolysin is a complex peptide mixture, making it difficult to attribute effects to specific components. The study was published in a lower-impact journal. The exact timing and duration of treatment are not detailed in the abstract."},{"rthcId":"RPEP-05811","title":"Scorpion Venom Antimicrobial Peptides Induce Siderophore Biosynthesis and Oxidative Stress Responses in Escherichia coli.","authors":"Tawfik, Mohamed M; Bertelsen, Magnus; Abdel-Rahman, Mohamed A; Strong, Peter N; Miller, Keith","year":2021,"journal":"mSphere, 6(3)","doi":"10.1128/mSphere.00267-21","pmid":"33980680","tags":["antimicrobial-peptides","venom-derived-peptides","infection-and-immunity"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Scorpion venom AMPs Smp24 and Smp43 kill E. coli through distinct intracellular mechanisms beyond membrane disruption, including iron transport and respiratory interference.","whyItMatters":"Understanding how antimicrobial peptides work inside bacteria could help design better antibiotics to fight drug-resistant infections.","specificNumbers":"Smp24: 24 aa, 72 downregulated + 52 upregulated genes; Smp43: 43 aa, 79 downregulated + 3 upregulated genes; 14 common; 10 resistant mutants to Smp24","methodology":"Lab study. Used DNA microarrays to measure gene expression changes in E. coli after peptide exposure. Tested knockout mutants for resistance changes.","limitations":"Only tested against E. coli in the lab. Effects on other bacteria or in living animals were not studied. Subinhibitory concentrations were used."},{"rthcId":"RPEP-05812","title":"Oral self-nanoemulsifying formulation of GLP-1 agonist peptide exendin-4: development, characterization and permeability assesment on Caco-2 cell monolayer.","authors":"Tekeli, Merve Celik; Aktas, Yesim; Celebi, Nevin","year":2021,"journal":"Amino acids, 53(1), 73-88","doi":"10.1007/s00726-020-02926-0","pmid":"33398527","tags":["peptide-drug-delivery","glp-1","bioavailability-and-absorption"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"A self-nanoemulsifying oral formulation increased exendin-4 intestinal permeability by 1.5-fold compared to a standard peptide solution.","whyItMatters":"Making injectable diabetes drugs available as pills would be more convenient and could improve treatment compliance.","specificNumbers":"Droplet size 18-50 nm; PDI 0.08-0.204; zeta potential -3 to -23 mV; 1.5-fold permeability increase; 1-month stability","methodology":"Lab study. Optimized formulation using Design of Experiment approach. Tested stability at two storage conditions for one month. Measured intestinal permeability using Caco-2 cell monolayers.","limitations":"Only tested on cells in a lab dish, not in animals or humans. A 1.5-fold improvement may not be enough for therapeutic levels in the body."},{"rthcId":"RPEP-05813","title":"Lutzomyia longipalpis Antimicrobial Peptides: Differential Expression during Development and Potential Involvement in Vector Interaction with Microbiota and Leishmania.","authors":"Telleria, Erich Loza; Tinoco-Nunes, Bruno; Leštinová, Tereza; de Avellar, Lívia Monteiro; Tempone, Antonio Jorge; Pitaluga, André Nóbrega; Volf, Petr; Traub-Csekö, Yara Maria","year":2021,"journal":"Microorganisms, 9(6)","doi":"10.3390/microorganisms9061271","pmid":"34207941","tags":["antimicrobial-peptides","infection-and-immunity","defensins"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Sand fly AMPs increase during feeding and Leishmania infection, but they primarily control bacteria rather than blocking parasite development.","whyItMatters":"Understanding how disease-carrying insects interact with parasites could reveal new ways to block disease transmission.","specificNumbers":"6 AMPs studied; attacin and defensin 2 upregulated by Leishmania; attacin silencing increased bacteria growth","methodology":"Lab study. Measured AMP gene expression by qPCR in larvae and adults under different feeding and infection conditions. Used gene silencing to test function.","limitations":"Study was in lab-reared sand flies. Natural conditions may differ. Gene silencing may not completely eliminate peptide function."},{"rthcId":"RPEP-05814","title":"Melittin, a honeybee venom derived peptide for the treatment of chemotherapy-induced peripheral neuropathy.","authors":"Tender, Tenzin; Rahangdale, Rakesh Ravishankar; Balireddy, Sridevi; Nampoothiri, Madhavan; Sharma, K Krishna; Raghu Chandrashekar, Hariharapura","year":2021,"journal":"Medical oncology (Northwood, London, England), 38(5), 52","doi":"10.1007/s12032-021-01496-9","pmid":"33796975","tags":["venom-derived-peptides","neuroprotection","pain-and-analgesia"],"studyType":"Review + Original Finding","evidenceStrength":"Moderate","keyFinding":"Melittin, the primary active peptide in honeybee venom, has shown therapeutic efficacy against chemotherapy-induced peripheral neuropathy (CIPN) caused by paclitaxel and oxaliplatin in preclinical studies. However, melittin's clinical use has been blocked by its tendency to destroy red blood cells (hemolysis).\n\nThe authors present an original finding that α-Crystallin, an eye lens protein, can inhibit melittin-induced hemolysis. This raises the possibility that a melittin/α-Crystallin combination could deliver the neuroprotective benefits of melittin while neutralizing its most dangerous side effect.","whyItMatters":"Chemotherapy-induced peripheral neuropathy affects up to 38% of patients on multi-drug regimens, causing pain, numbness, and motor dysfunction that can persist long after treatment ends. Current options — opioids, NSAIDs, and antidepressants — offer only short-term symptom relief with their own side effects. Melittin could fill this therapeutic gap if its toxicity problem is solved, and the α-Crystallin discovery offers a concrete path forward.","specificNumbers":"5% CIPN rate with single-agent chemo · Up to 38% with multi-agent chemo · α-Crystallin inhibits melittin hemolysis · Efficacy shown against paclitaxel and oxaliplatin CIPN","methodology":"This is a hybrid publication combining a narrative review of existing research on melittin for CIPN with an original laboratory finding. The review synthesizes preclinical evidence for melittin's neuroprotective effects. The original component demonstrates that α-Crystallin protein can inhibit melittin-induced hemolysis in vitro, presenting a potential strategy for overcoming melittin's key safety limitation.","limitations":"This is primarily a review article, not a clinical trial. The α-Crystallin finding is preliminary and needs extensive validation in animal models and eventually human studies. No human clinical trials of melittin for CIPN have been conducted. The feasibility of combining melittin with α-Crystallin for therapeutic use — including dosing, delivery, and pharmacokinetics — remains unexplored."},{"rthcId":"RPEP-05815","title":"Unravelling cytosolic delivery of cell penetrating peptides with a quantitative endosomal escape assay.","authors":"Teo, Serena L Y; Rennick, Joshua J; Yuen, Daniel; Al-Wassiti, Hareth; Johnston, Angus P R; Pouton, Colin W","year":2021,"journal":"Nature communications, 12(1), 3721","doi":"10.1038/s41467-021-23997-x","pmid":"34140497","tags":["cell-penetrating-peptides","peptide-drug-delivery","bioavailability-and-absorption"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"The SLEEQ (Split Luciferase Endosomal Escape Quantification) assay was developed as a highly sensitive tool for quantifying cytosolic delivery of CPP-protein fusions. Testing multiple widely studied cell-penetrating peptides revealed that positively charged CPPs enhanced cytosolic delivery by increasing non-specific cell membrane association — not by improving endosomal escape efficiency.\n\nThis is a paradigm-changing finding: the field had largely assumed CPPs work by facilitating endosomal escape (helping cargo leave endosomal compartments to reach the cytosol). Instead, CPPs simply increase the total amount of cargo that associates with cells, and the same proportion escapes endosomes regardless of CPP presence.","whyItMatters":"Billions of research dollars have been spent trying to improve endosomal escape as the key bottleneck in intracellular drug delivery. This study suggests that for CPPs, the bottleneck is actually membrane association — getting more cargo to stick to cells in the first place. This fundamentally redirects drug delivery research: instead of engineering better endosomal escape, scientists should focus on enhancing membrane binding for CPP-based therapies.","specificNumbers":"Multiple CPPs tested; positively charged CPPs showed increased membrane association; SLEEQ assay developed","methodology":"Researchers developed the SLEEQ assay using split luciferase complementation to directly and quantitatively measure cytosolic delivery of protein cargo. Multiple widely studied CPPs were fused to a model protein and tested in cell culture. The assay distinguished between total cellular uptake and actual cytosolic delivery, allowing researchers to calculate endosomal escape efficiency independently of uptake. This resolved conflicting results from previous less sensitive and indirect assays.","limitations":"All experiments were performed in cell culture, which may not capture the complexity of in vivo delivery where protein corona formation, immune clearance, and tissue barriers are present. Only one model protein cargo was tested — different cargo types (nucleic acids, smaller peptides) may interact differently with CPPs. The SLEEQ assay requires genetic modification of cells, which limits its application to laboratory settings. The findings may not apply to all CPP types or all cell types."},{"rthcId":"RPEP-05816","title":"Deterioration of headache impact and health-related quality of life in migraine patients after cessation of preventive treatment with CGRP(-receptor) antibodies.","authors":"Terhart, Maria; Mecklenburg, Jasper; Neeb, Lars; Overeem, Lucas Hendrik; Siebert, Anke; Steinicke, Maureen; Raffaelli, Bianca; Reuter, Uwe","year":2021,"journal":"The journal of headache and pain, 22(1), 158","doi":"10.1186/s10194-021-01368-7","pmid":"34972502","tags":["cgrp","migraine-and-headache","clinical-applications"],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"All quality of life measures worsened significantly within 16 weeks of stopping CGRP antibody treatment, exceeding minimally clinically important differences.","whyItMatters":"Guidelines recommend stopping CGRP treatment periodically. This study shows that stopping leads to real, measurable worsening that patients and doctors should plan for.","specificNumbers":"61 patients; HIT-6 +3.69 (p<0.001); EQ-5D-5L -0.07 (p=0.013); PCS-12 -4.04 (p=0.013); MCS-12 -2.73 (p=0.003); 16-week follow-up","methodology":"Prospective cohort study. Followed 61 chronic migraine patients at three time points: last injection, 8 weeks later, and 16 weeks later. Used HIT-6, EQ-5D-5L, and SF-12 questionnaires.","limitations":"Small sample (61 patients). No control group. Observational design cannot prove causation. Most patients were female."},{"rthcId":"RPEP-05817","title":"Determination of ghrelin and desacyl ghrelin in human plasma and urine by means of LC-MS/MS for doping controls.","authors":"Thomas, Andreas; Krombholz, Sophia; Wolf, Carina; Thevis, Mario","year":2021,"journal":"Drug testing and analysis, 13(11-12), 1862-1870","doi":"10.1002/dta.3176","pmid":"34633773","tags":["ghrelin","growth-hormone-axis","peptide-detection-and-analysis"],"studyType":"methods","evidenceStrength":"moderate","keyFinding":"LC-MS/MS methods were successfully validated for ghrelin (G) and desacyl ghrelin (DAG) in plasma and urine. Limits of detection were 30-50 pg/mL with recoveries of 45-50% and imprecisions of 3-24%. Plasma quantification showed accuracies of ~100% for G and ~106% for DAG.\n\nHealthy volunteer plasma levels ranged from 30-100 pg/mL for ghrelin and 100-1200 pg/mL for desacyl ghrelin. Critically, no endogenous ghrelin or desacyl ghrelin was detected in urine by this mass spectrometry approach, despite adequate sensitivity — contradicting earlier studies that used ligand binding assays. The method performed well at just 5% of WADA's minimum required performance level of 2 ng/mL in urine.","whyItMatters":"Ghrelin is a WADA-banned substance, but detecting its misuse requires reliable analytical methods. This study reveals that urine-based ghrelin testing — the standard approach for most doping controls — may be fundamentally flawed because ghrelin doesn't appear to be present in urine at detectable levels. This has significant implications for how anti-doping labs approach peptide hormone testing.","specificNumbers":"LOD 30-50 pg/mL; recovery 45-50%; imprecision 3-24%; blood ghrelin 30-100 pg/mL; DAG 100-1200 pg/mL; WADA MRPL 2 ng/mL","methodology":"Two LC-MS/MS strategies were developed: a bottom-up approach (peptide digestion) for plasma and a top-down approach (intact peptide analysis) for urine. Both used solid-phase extraction for sample enrichment and cleanup. Methods were validated for limits of detection, recovery, precision, and accuracy. Plasma from healthy volunteers was analyzed as proof of concept.","limitations":"Only a small number of healthy volunteers were tested — no samples from individuals who actually used exogenous ghrelin were available. The absence of ghrelin in urine contradicts earlier immunoassay-based findings but needs independent confirmation. The study did not assess whether exogenously administered ghrelin might appear in urine at higher concentrations than endogenous levels."},{"rthcId":"RPEP-05818","title":"Dual GIP and GLP-1 Receptor Agonist Tirzepatide Improves Beta-cell Function and Insulin Sensitivity in Type 2 Diabetes.","authors":"Thomas, Melissa K; Nikooienejad, Amir; Bray, Ross; Cui, Xuewei; Wilson, Jonathan; Duffin, Kevin; Milicevic, Zvonko; Haupt, Axel; Robins, Deborah A","year":2021,"journal":"The Journal of clinical endocrinology and metabolism, 106(2), 388-396","doi":"10.1210/clinem/dgaa863","pmid":"33236115","tags":["glp-1","gip","diabetes-and-metabolism","weight-management"],"studyType":"clinical-trial","evidenceStrength":"strong","keyFinding":"Tirzepatide improved insulin sensitivity beyond what weight loss alone could explain, with weight loss accounting for only 13-21% of HOMA2-IR improvement.","whyItMatters":"Tirzepatide's insulin-sensitizing effects go beyond weight loss, suggesting it works through unique mechanisms that single-target drugs do not provide.","specificNumbers":"316 patients; 47 sites; 26 weeks; tirzepatide 1/5/10/15 mg; dulaglutide 1.5 mg; weight loss explained 13-21% of HOMA2-IR improvement; p≤0.007 for proinsulin ratios","methodology":"Post hoc analysis of a 26-week randomized controlled trial. 316 patients with type 2 diabetes received tirzepatide (1, 5, 10, or 15 mg), dulaglutide (1.5 mg), or placebo. Analyzed fasting biomarkers and used regression analysis.","limitations":"Post hoc analysis, not the primary study endpoint. 26-week duration may not capture long-term effects. Study population may not represent all diabetes patients."},{"rthcId":"RPEP-05819","title":"The Pro-Gly or Hyp-Gly Containing Peptides from Absorbates of Fish Skin Collagen Hydrolysates Inhibit Platelet Aggregation and Target P2Y12 Receptor by Molecular Docking.","authors":"Tian, Qi; Li, Shi-Ming; Li, Bo","year":2021,"journal":"Foods (Basel, Switzerland), 10(7)","doi":"10.3390/foods10071553","pmid":"34359423","tags":["collagen-peptides","cardiovascular-health","bioactive-peptides"],"studyType":"animal","evidenceStrength":"preliminary","keyFinding":"Collagen peptide OGSA inhibited platelet aggregation (IC50 = 0.63 mM) and prevented clots in rats without bleeding risk, likely by targeting the P2Y12 receptor.","whyItMatters":"Natural peptides from food sources that prevent blood clots without causing bleeding could become safer alternatives to current blood thinners.","specificNumbers":"11 peptides; 9 with PG/OG; OGSA IC50 0.63 mM; 200 micromol/kg in rats; P2Y12 binding at Cys97, Ser101, Lys179","methodology":"Lab and animal study. Isolated peptides from fish skin collagen hydrolysates using HPLC-MS/MS. Tested platelet aggregation in vitro and thrombus formation in rats. Used molecular docking to identify the target.","limitations":"Animal study in rats. Molecular docking is computational prediction, not proven binding. Human clinical data is needed."},{"rthcId":"RPEP-05820","title":"Mechanical Enhancement and Kinetics Regulation of Fmoc-Diphenylalanine Hydrogels by Thioflavin T.","authors":"Tikhonova, Tatiana N; Rovnyagina, Nataliya N; Arnon, Zohar A; Yakimov, Boris P; Efremov, Yuri M; Cohen-Gerassi, Dana; Halperin-Sternfeld, Michal; Kosheleva, Nastasia V; Drachev, Vladimir P; Svistunov, Andrey A; Timashev, Peter S; Adler-Abramovich, Lihi; Shirshin, Evgeny A","year":2021,"journal":"Angewandte Chemie (International ed. in English), 60(48), 25339-25345","doi":"10.1002/anie.202107063","pmid":"34590774","tags":["peptide-self-assembly","biomaterials-and-scaffolds","peptide-engineering"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"ThT slowed Fmoc-FF gelation tenfold while increasing gel rigidity tenfold and creating shorter, denser fibers with higher thermal stability.","whyItMatters":"Controlling gel strength and formation speed is critical for biomaterial applications like tissue engineering and drug delivery scaffolds.","specificNumbers":"10x gelation time increase; 10x rigidity increase; shorter denser fibers; higher thermal stability","methodology":"Lab study. Mixed ThT with Fmoc-FF peptide solutions. Measured gelation time, rheology (stiffness), fiber morphology, and thermal stability.","limitations":"Lab study only. Practical applications in medicine were not tested. ThT itself has biological activity that could complicate medical use."},{"rthcId":"RPEP-05821","title":"Chiral Orchestration: A Tool for Fishing Out Tripeptide-Based Mechanoresponsive Supergelators Possessing Anti-Inflammatory and Antimicrobial Properties.","authors":"Tiwari, Priyanka; Gupta, Arindam; Shukla, Durgesh Nandan; Mishra, Ankit K; Basu, Anindya; Dutt Konar, Anita","year":2021,"journal":"ACS applied bio materials, 4(5), 4119-4130","doi":"10.1021/acsabm.0c01513","pmid":"35006826","tags":["antimicrobial-peptides","peptide-self-assembly","biomaterials-and-scaffolds"],"studyType":"animal","evidenceStrength":"preliminary","keyFinding":"All four chirally tuned tripeptide hydrogels formed mechanoresponsive (self-healing) nanofibrillar networks under physiological conditions. The gels demonstrated antimicrobial activity against both Gram-positive bacteria (Staphylococcus aureus and Streptococcus mutans) and Gram-negative bacteria (Escherichia coli and Klebsiella pneumonia).\n\nCritically, the hydrogels were biocompatible with mammalian cells as confirmed by MTT viability assays, hemolysis tests, and lipid peroxidation assays. Anti-inflammatory activity was validated through MMP2/MMP9 inhibition studies in vitro and a rat pouch model for acute inflammation in vivo. The inclusion of D-amino acids at specific positions allowed fine-tuning of the gels' mechanical strength.","whyItMatters":"Infections and inflammation often go hand in hand — especially around surgical implants and wounds. Materials that can simultaneously fight bacteria and calm inflammation could simplify treatment and improve outcomes. These peptide hydrogels are also self-healing, meaning they can recover after being injected or mechanically stressed, making them practical for real-world medical applications.","specificNumbers":"4 stereoisomers; 4 bacterial species; MMP2/MMP9 inhibition; rat pouch inflammation model; biocompatible by MTT and hemolysis","methodology":"The researchers synthesized four stereoisomers of a tripeptide hydrogelator by systematically varying the chirality (L vs. D) of two phenylalanine residues. They characterized the gels' structure and mechanical properties using spectroscopy and imaging. Antimicrobial activity was tested against four bacterial species. Biocompatibility was assessed using MTT assays, hemolysis tests, and lipid peroxidation assays on mammalian cells. Anti-inflammatory effects were evaluated via MMP2/MMP9 enzyme inhibition in vitro and a rat air-pouch inflammation model in vivo.","limitations":"This is early-stage research tested against only four bacterial species. Long-term safety and efficacy in living systems have not been established. The specific minimum inhibitory concentrations and dose-response relationships are not detailed in the abstract. The rat inflammation model, while informative, is a simplified representation of clinical inflammation scenarios. No comparison to existing antimicrobial or anti-inflammatory standard-of-care treatments was described."},{"rthcId":"RPEP-05822","title":"Physiological and Immunological Status of Adult Honeybees (Apis mellifera) Fed Sugar Syrup Supplemented with Pentadecapeptide BPC 157.","authors":"Tlak Gajger, Ivana; Smodiš Škerl, Maja Ivana; Šoštarić, Petra; Šuran, Jelena; Sikirić, Predrag; Vlainić, Josipa","year":2021,"journal":"Biology, 10(9)","doi":"10.3390/biology10090891","pmid":"34571768","tags":["bpc-157","bioactive-peptides","immune-system"],"studyType":"animal","evidenceStrength":"preliminary","keyFinding":"BPC 157 supplementation improved honeybee hemolymph biochemistry, immune markers, hypopharyngeal gland function, and mid-gut digestive enzyme activity.","whyItMatters":"Bee population decline threatens food production. Finding supplements that boost bee health could help protect pollinator populations.","specificNumbers":"Improved glucose, trehalose, lipids, proteins, vitellogenin, GOX; increased LAP activity in mid-gut epithelial cells","methodology":"Combined lab-controlled and field study. Fed BPC 157 in sugar syrup to newly emerged worker bees. Measured hemolymph biochemistry, glucose-oxidase, vitellogenin, hypopharyngeal gland development, and leucine aminopeptidase activity in mid-guts.","limitations":"Animal study in bees, not humans. Mechanism of action in bees is unclear. Long-term effects on colony health not measured."},{"rthcId":"RPEP-05823","title":"Glucagon-like peptide-1 receptor agonist inhibits aeroallergen-induced activation of ILC2 and neutrophilic airway inflammation in obese mice.","authors":"Toki, Shinji; Newcomb, Dawn C; Printz, Richard L; Cahill, Katherine N; Boyd, Kelli L; Niswender, Kevin D; Peebles, R Stokes","year":2021,"journal":"Allergy, 76(11), 3433-3445","doi":"10.1111/all.14879","pmid":"33955007","tags":["glp-1","immune-system","respiratory-health"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"GLP-1RA reduced allergen-induced airway neutrophilia and multiple inflammatory cytokines in obese mice, an effect not achieved by TSLP or ST2 inhibition alone.","whyItMatters":"GLP-1 drugs are already approved for diabetes and obesity. If they also help airway inflammation, obese asthma patients could get dual benefits from one treatment.","specificNumbers":"4-day challenge; reduced IL-5, IL-13, CCL11, CXCL1, CXCL5, TSLP, IL-33; decreased ICAM-1; blocked airway neutrophilia","methodology":"Animal study. Compared lean (SWR) and obese (TALLYHO) mice challenged with Alternaria alternata extract. Treated with GLP-1RA or vehicle for 4 days. Measured airway cells, cytokines, and surface markers.","limitations":"Animal study in mice. Obese mouse strains do not perfectly model human obesity-related asthma. Short 4-day challenge does not mimic chronic asthma."},{"rthcId":"RPEP-05824","title":"Effectiveness of dual migraine therapy with CGRP inhibitors and onabotulinumtoxinA injections: case series.","authors":"Toni, Tahlia; Tamanaha, Rayce; Newman, Bashak; Liang, Yutong; Lee, James; Carrazana, Enrique; Vajjala, Vimala; Viereck, Jason; Liow, Kore Kai","year":2021,"journal":"Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 42(12), 5373-5376","doi":"10.1007/s10072-021-05547-x","pmid":"34409517","tags":["cgrp","migraine-and-headache","clinical-applications"],"studyType":"case-series","evidenceStrength":"low","keyFinding":"Dual therapy with CGRP inhibitors and onabotulinumtoxinA reduced headache days by 9 per month (p=0.007) and pain severity by 3 points (p=0.0007).","whyItMatters":"Clinical trials excluded this combination, so real-world data is needed. These results support using both treatments together for difficult-to-treat migraines.","specificNumbers":"17 patients; 16F/1M; 9 fremanezumab, 4 erenumab, 4 galcanezumab; headache days 27.6→18.6 (p=0.007); pain 8.4→5.4 (p=0.0007)","methodology":"Retrospective case series. 17 chronic migraine patients with suboptimal Botox response who added a CGRP inhibitor. Compared headache days and severity before and 1-6 months after adding treatment.","limitations":"Very small case series (17 patients). No control group. Not a randomized trial. Short follow-up (1-6 months)."},{"rthcId":"RPEP-05825","title":"The seven constitutive respiratory defense barriers against SARS-CoV-2 infection.","authors":"Tosta, Eduardo","year":2021,"journal":"Revista da Sociedade Brasileira de Medicina Tropical, 54, e04612021","doi":"10.1590/0037-8682-0461-2021","pmid":"34932765","tags":["defensins","antimicrobial-peptides","infection-and-immunity","respiratory-health"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"The review identifies seven constitutive respiratory defense barriers against SARS-CoV-2:\n\n1. Mucus and mucociliary clearance\n2. Surfactants (inhibit viral invasion, enhance phagocytosis)\n3. Respiratory microbiota (activates immune cells, induces defensins and IgA)\n4. Antimicrobial peptides — defensins and lactoferrin (direct antiviral activity, inhibit viral fusion, modulate immunity)\n5. Secretory IgA antibodies (inhibit viral cell invasion)\n6. Respiratory epithelial cells (restrict receptor access, produce interferons, lactoferrin, defensins)\n7. Innate immune cell sensing (triggers adaptive immunity cascade)\n\nAntimicrobial peptides feature prominently in barriers 4 and 6, highlighting their central role in respiratory defense.","whyItMatters":"Most COVID-19 research focused on adaptive immunity (antibodies and T cells), but innate defenses determine whether the virus ever gains a foothold. Antimicrobial peptides like defensins — which directly kill viruses and block their entry — may explain why some people are naturally more resistant to infection. Understanding these barriers could inform development of prophylactic treatments that boost natural defenses.","specificNumbers":"7 defense barriers identified and characterized","methodology":"Narrative review synthesizing published research on innate respiratory defense mechanisms against SARS-CoV-2, organized as seven sequential barriers from the airway surface to innate immune cell activation.","limitations":"This is a narrative review published in 2021 when understanding of SARS-CoV-2 was still evolving. Some mechanisms described may have been revised as new data emerged. The relative importance of each barrier in determining clinical outcomes is not quantified. Individual variation in barrier effectiveness — which likely determines susceptibility — is discussed qualitatively but not systematically."},{"rthcId":"RPEP-05826","title":"Evaluation of Efficient Non-reducing Enzymatic and Chemical Ligation Strategies for Complex Disulfide-Rich Peptides.","authors":"Tran, Hue N T; Tran, Poanna; Deuis, Jennifer R; McMahon, Kirsten L; Yap, Kuok; Craik, David J; Vetter, Irina; Schroeder, Christina I","year":2021,"journal":"Bioconjugate chemistry, 32(11), 2407-2419","doi":"10.1021/acs.bioconjchem.1c00452","pmid":"34751572","tags":["venom-derived-peptides","peptide-engineering","pain-and-analgesia"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Sortase A5° achieved 60% ligation of two disulfide-rich venom peptides in 15 minutes while maintaining correct folding and NaV1.7 inhibitory activity.","whyItMatters":"Double-knotted peptides could become powerful pain drugs. Having an efficient way to make them is essential for research and development.","specificNumbers":"60% ligation in 15 min; sortase A5° most efficient; 5 enzymatic + 1 chemical method; PaurTx3 + KIIIA targeting hNaV1.7","methodology":"Lab study. Compared 5 enzymatic and 1 chemical ligation method for joining pre-folded, disulfide-rich peptides. Tested activity on NaV1.7 channels using electrophysiology.","limitations":"Lab study only. These linked peptides have not been tested in animals or humans. Manufacturing at scale could be challenging."},{"rthcId":"RPEP-05827","title":"Utilisation of compounds from venoms in drug discovery.","authors":"Trim, Carol M; Byrne, Lee J; Trim, Steven A","year":2021,"journal":"Progress in medicinal chemistry, 60, 1-66","doi":"10.1016/bs.pmch.2021.01.001","pmid":"34147202","tags":["venom-derived-peptides","peptide-drug-delivery","clinical-applications"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Venom-derived compounds have produced successful drugs and represent a largely untapped source of stable molecules for difficult drug targets.","whyItMatters":"Many disease targets are too complex for traditional small molecules but too simple for antibodies. Venom peptides fill this gap.","specificNumbers":"Approved drugs: exenatide, eptifibatide, echistatin; venom sources from 7+ animal groups","methodology":"Review article covering venom biology, drug discovery examples, and challenges in developing venom-derived therapeutics.","limitations":"This is a review, not original research. Many venom compounds face challenges in oral absorption, manufacturing, and toxicity."},{"rthcId":"RPEP-05828","title":"Genetic, cellular, and structural characterization of the membrane potential-dependent cell-penetrating peptide translocation pore.","authors":"Trofimenko, Evgeniya; Grasso, Gianvito; Heulot, Mathieu; Chevalier, Nadja; Deriu, Marco A; Dubuis, Gilles; Arribat, Yoan; Serulla, Marc; Michel, Sebastien; Vantomme, Gil; Ory, Florine; Dam, Linh Chi; Puyal, Julien; Amati, Francesca; Lüthi, Anita; Danani, Andrea; Widmann, Christian","year":2021,"journal":"eLife, 10","doi":"10.7554/eLife.69832","pmid":"34713805","tags":["cell-penetrating-peptides","peptide-drug-delivery","peptide-engineering"],"studyType":"animal","evidenceStrength":"strong","keyFinding":"CPPs enter cells through megapolarization-induced water pores (2-5 nm), regulated by KCNQ5, KCNN4, and KCNK5 potassium channels, confirmed in zebrafish and mouse models.","whyItMatters":"Understanding exactly how CPPs enter cells allows scientists to design better drug delivery systems that get more cargo inside cells.","specificNumbers":"3 K+ channels (KCNQ5, KCNN4, KCNK5); megapolarization <-150 mV; pore diameter 2-5 nm; validated in vivo","methodology":"CRISPR/Cas9 screen to identify genetic modulators. In silico modeling of pore formation. Live cell experiments with dyes of varying sizes. In vivo validation in zebrafish and mouse models.","limitations":"The megapolarization model may not apply equally to all cell types. In vivo validation was limited to specific tissues."},{"rthcId":"RPEP-05829","title":"A Series of Novel, Highly Potent, and Orally Bioavailable Next-Generation Tricyclic Peptide PCSK9 Inhibitors.","authors":"Tucker, Thomas J; Embrey, Mark W; Alleyne, Candice; Amin, Rupesh P; Bass, Alan; Bhatt, Bhavana; Bianchi, Elisabetta; Branca, Danila; Bueters, Tjerk; Buist, Nicole; Ha, Sookhee N; Hafey, Mike; He, Huaibing; Higgins, John; Johns, Douglas G; Kerekes, Angela D; Koeplinger, Kenneth A; Kuethe, Jeffrey T; Li, Nianyu; Murphy, BethAnn; Orth, Peter; Salowe, Scott; Shahripour, Aurash; Tracy, Rodger; Wang, Weixun; Wu, Chengwei; Xiong, Yusheng; Zokian, Hratch J; Wood, Harold B; Walji, Abbas","year":2021,"journal":"Journal of medicinal chemistry, 64(22), 16770-16800","doi":"10.1021/acs.jmedchem.1c01599","pmid":"34704436","tags":["peptide-drug-delivery","cardiovascular-health","bioavailability-and-absorption"],"studyType":"animal","evidenceStrength":"strong","keyFinding":"Starting from earlier lead compounds, the researchers optimized a series of bi- and tricyclic peptide structures to create compound 44, which demonstrated sufficient oral bioavailability in both rats and cynomolgus monkeys to maintain therapeutic blood levels using an enabled formulation.\n\nWhen tested in monkeys, the optimized peptides achieved target engagement and LDL cholesterol lowering essentially identical to the clinically approved injectable PCSK9 antibodies (evolocumab and alirocumab). This represents the first demonstration that macrocyclic peptides can match antibody-level efficacy through oral delivery for this target.","whyItMatters":"Millions of people worldwide take injectable PCSK9 antibodies like Repatha (evolocumab) and Praluent (alirocumab) to manage high cholesterol and reduce heart disease risk. However, the need for regular injections limits who is willing to use them. A once-daily oral pill that works just as well could dramatically increase the number of patients who benefit from PCSK9-targeted therapy, similar to how statins became widely used because of their convenience.","specificNumbers":"Oral bioavailability in 2 species; LDL lowering equivalent to approved antibodies; once-daily oral potential; compound 44 lead candidate","methodology":"This was a medicinal chemistry optimization study. The team designed and synthesized a series of bi- and tricyclic peptide PCSK9 inhibitors, refining their chemical structures to improve potency and oral absorption. They used X-ray crystallography to understand how the peptides bind their target. The best candidates were tested in rats and cynomolgus monkeys for oral bioavailability, and the lead compound was evaluated in monkeys for its ability to engage PCSK9 and lower LDL cholesterol levels.","limitations":"All testing was done in animals (rats and monkeys), with no human data yet available. The oral formulation required special 'enabled' delivery technology, meaning a standard pill might not work. Long-term safety has not been established. Sample sizes for the animal studies were not specified in the abstract, and it remains to be seen whether the results will translate to humans."},{"rthcId":"RPEP-05830","title":"PhytoAFP: In Silico Approaches for Designing Plant-Derived Antifungal Peptides.","authors":"Tyagi, Atul; Roy, Sudeep; Singh, Sanjay; Semwal, Manoj; Shasany, Ajit K; Sharma, Ashok; Provazník, Ivo","year":2021,"journal":"Antibiotics (Basel, Switzerland), 10(7)","doi":"10.3390/antibiotics10070815","pmid":"34356736","tags":["antimicrobial-peptides","peptide-engineering","computational-peptide-design"],"studyType":"computational","evidenceStrength":"moderate","keyFinding":"An SVM-based prediction model identified plant antifungal peptides with 94.4% accuracy and 0.89 MCC using amino acid composition features.","whyItMatters":"Fungal infections are rising and drug resistance is growing. AI tools that predict antifungal peptides could accelerate drug discovery.","specificNumbers":"94.4% accuracy; MCC 0.89; preferred residues C, G, K, R, S; motifs NYVF, NYVFP, YVFP, NYVFPA, VFPA","methodology":"Computational study. Built support vector machine models using mono-, di-, and tripeptide composition, binary, hybrid, and physicochemical features. Validated with cross-validation.","limitations":"Computational predictions need experimental validation. Model accuracy depends on the quality of training data. Not all predicted peptides will work in practice."},{"rthcId":"RPEP-05831","title":"Targeted oral peptide delivery using multi-unit particulates: Drug and permeation enhancer layering approach.","authors":"Tyagi, Puneet; Trivedi, Ruchit; Pechenov, Sergei; Patel, Chandresh; Revell, Jefferson; Wills, Sarah; Huang, Yue; Rosenbaum, Anton I; Subramony, J Anand","year":2021,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 338, 784-791","doi":"10.1016/j.jconrel.2021.09.002","pmid":"34499981","tags":["peptide-drug-delivery","bioavailability-and-absorption","peptide-engineering"],"studyType":"animal","evidenceStrength":"preliminary","keyFinding":"Multi-layered oral peptide particles with permeation enhancers showed improved bioavailability in dogs, with higher disintegration pH being most effective.","whyItMatters":"Most peptide drugs require injection. This layered approach could make oral peptide pills practical for conditions like diabetes.","specificNumbers":"Disintegration pH 5.5 and 7.0; high-pH improved bioavailability; fluidized bed layering technique; sustained-release and mucoadhesive coatings","methodology":"Formulation development study. Created layered particles using fluidized bed coating. Tested dissolution in vitro and pharmacokinetics in beagle dogs.","limitations":"Tested in dogs, not humans. Specific peptide and bioavailability numbers not detailed in abstract. Dog gut physiology differs from human."},{"rthcId":"RPEP-05832","title":"Functional and Bioactive Properties of Peptides Derived from Marine Side Streams.","authors":"Ucak, Ilknur; Afreen, Maliha; Montesano, Domenico; Carrillo, Celia; Tomasevic, Igor; Simal-Gandara, Jesus; Barba, Francisco J","year":2021,"journal":"Marine drugs, 19(2)","doi":"10.3390/md19020071","pmid":"33572713","tags":["collagen-peptides","bioactive-peptides","cardiovascular-health"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Fish processing waste contains peptides with antioxidant, antihypertensive, anticoagulant, and immunomodulatory activities applicable to food and pharmaceutical industries.","whyItMatters":"Turning fish waste into valuable health products reduces environmental impact and creates new revenue from what is currently discarded.","specificNumbers":"Sources: skin, bones, heads, viscera; methods: enzymatic hydrolysis, fermentation; activities: antioxidant, antihypertensive, anticoagulant, immunomodulatory","methodology":"Review article covering methods for extracting bioactive peptides from seafood side streams and their biological activities and applications.","limitations":"This is a review, not original research. Many bioactive peptides identified in the lab have not been tested in humans. Processing methods affect peptide quality."},{"rthcId":"RPEP-05833","title":"Lipid-Based Ionic-Liquid-Mediated Nanodispersions as Biocompatible Carriers for the Enhanced Transdermal Delivery of a Peptide Drug.","authors":"Uddin, Shihab; Islam, Md Rafiqul; Chowdhury, Md Raihan; Wakabayashi, Rie; Kamiya, Noriho; Moniruzzaman, Muhammad; Goto, Masahiro","year":2021,"journal":"ACS applied bio materials, 4(8), 6256-6267","doi":"10.1021/acsabm.1c00563","pmid":"35006923","tags":["peptide-drug-delivery","bioavailability-and-absorption","peptide-engineering"],"studyType":"animal","evidenceStrength":"preliminary","keyFinding":"Ionic liquid nanodispersions significantly increased transdermal delivery of leuprolide in vitro and in vivo while maintaining biocompatibility.","whyItMatters":"Transdermal delivery avoids needles and stomach degradation. This approach could make peptide drugs available as skin patches or creams.","specificNumbers":"5:5 wt% IL/Span-20 optimal; 10 wt% total surfactant in IPM; EDMPC-based LBILs; significant permeation increase","methodology":"Formulation development. Created ionic liquid-in-oil nanodispersions. Characterized size and stability. Tested skin permeation in vitro and in vivo. Evaluated cytotoxicity.","limitations":"Tested with one peptide (leuprolide). In vivo results in animals may not translate directly to human skin. Long-term skin safety not assessed."},{"rthcId":"RPEP-05834","title":"Attenuation of nociceptive and paclitaxel-induced neuropathic pain by targeting inflammatory, CGRP and substance P signaling using 3-Hydroxyflavone.","authors":"Ullah, Rahim; Ali, Gowhar; Subhan, Fazal; Naveed, Muhammad; Khan, Ajmal; Khan, Jawad; Halim, Sobia Ahsan; Ahmad, Nisar; Zakiullah; Al-Harrasi, Ahmed","year":2021,"journal":"Neurochemistry international, 144, 104981","doi":"10.1016/j.neuint.2021.104981","pmid":"33549629","tags":["cgrp","substance-p","pain-and-analgesia","neuroprotection"],"studyType":"animal","evidenceStrength":"preliminary","keyFinding":"3-Hydroxyflavone reduced paclitaxel-induced neuropathic pain in rats by suppressing spinal cord CGRP, substance P, and inflammatory cytokines, with NK1R as the likely primary target.","whyItMatters":"Chemotherapy-induced nerve pain has no good treatments. A compound that targets multiple pain pathways could be more effective than current options.","specificNumbers":"Paclitaxel 4 mg/kg days 1,3,5,7; reduced TNF-a, IL-1b, IL-6, CGRP, substance P mRNA; NK1R predicted strongest binding target","methodology":"Animal study. Induced peripheral neuropathy with paclitaxel (4 mg/kg on days 1, 3, 5, 7) in rats. Treated with 3HF. Measured pain behaviors, spinal cord gene expression (RT-PCR), and computational docking.","limitations":"Animal study in rats. Computational docking is prediction, not proven binding. 3HF has not been tested in humans for this use. Specific dose not detailed."},{"rthcId":"RPEP-05835","title":"GLP-1 and GIP receptor agonists in the treatment of Parkinson's disease: Translational systematic review and meta-analysis protocol of clinical and preclinical studies.","authors":"Vaccari, Carolina; Grotto, Denise; Pereira, Tiago da V; de Camargo, João Lauro V; Lopes, Luciane C","year":2021,"journal":"PloS one, 16(8), e0255726","doi":"10.1371/journal.pone.0255726","pmid":"34383800","tags":["glp-1","gip","brain-and-cognition","neuroprotection"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"This is a protocol for a systematic review, not findings. It aims to evaluate GLP-1 and GIP drugs for Parkinson's disease across preclinical and clinical studies.","whyItMatters":"Current Parkinson's drugs only manage symptoms. GLP-1 drugs might actually slow disease progression by protecting brain cells.","specificNumbers":"6 databases; PROSPERO CRD42020223435; preclinical + clinical studies; UPDRS as clinical outcome","methodology":"Systematic review protocol. Will search 6 databases for preclinical (rodent/primate) and clinical (RCT) studies. Will assess locomotor improvements, adverse effects, and UPDRS scores. Risk of bias by SYRCLE and Cochrane tools.","limitations":"This is a protocol, not results. The review has not been completed. Quality of findings will depend on available studies."},{"rthcId":"RPEP-05836","title":"Simplified Monopalmitoyl Toll-like Receptor 2 Ligand Mini-UPam for Self-Adjuvanting Neoantigen-Based Synthetic Cancer Vaccines.","authors":"van den Ende, Thomas C; Heuts, Jeroen M M; Gential, Geoffroy P P; Visser, Marten; van de Graaff, Michel J; Ho, Nataschja I; Jiskoot, Wim; Valentijn, A Rob P M; Meeuwenoord, Nico J; Overkleeft, Herman S; Codée, Jeroen D C; van der Burg, Sjoerd H; Verdegaal, Els M E; van der Marel, Gijsbert A; Ossendorp, Ferry; Filippov, Dmitri V","year":2021,"journal":"Chembiochem : a European journal of chemical biology, 22(7), 1215-1222","doi":"10.1002/cbic.202000687","pmid":"33180981","tags":["peptide-vaccines","cancer-and-oncology-peptides","immune-system"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Mini-UPam with one palmitoyl chain maintained TLR2 adjuvant activity while improving solubility and manufacturing of peptide-based cancer vaccines.","whyItMatters":"Personalized cancer vaccines need to be made quickly for each patient. Simpler, more soluble adjuvant-peptide conjugates speed up manufacturing.","specificNumbers":"1 vs 3 palmitoyl chains; Fmoc solid-phase synthesis; melanoma neoepitopes; patient T-cell activation confirmed","methodology":"Lab study. Designed and synthesized mini-UPam building block. Attached to clinically relevant melanoma neoepitopes via solid-phase synthesis. Tested immunogenicity using patient-derived T cells.","limitations":"Lab study only. Tested with T cells from one patient. In vivo efficacy in animals or clinical trials not reported."},{"rthcId":"RPEP-05837","title":"Dumping Syndrome and Postbariatric Hypoglycemia: Supporting Evidence for a Common Etiology.","authors":"van Furth, A Marrit; de Heide, Loek J M; Emous, Marloes; Veeger, Nic; van Beek, André P","year":2021,"journal":"Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery, 17(11), 1912-1918","doi":"10.1016/j.soard.2021.05.020","pmid":"34144916","tags":["glp-1","peptide-yy","diabetes-and-metabolism","gut-health"],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"GLP-1 and PYY were elevated in dumping syndrome patients both early and late after meals, correlating with symptoms and supporting a shared etiology with post-bariatric hypoglycemia.","whyItMatters":"Understanding that these complications share a cause could lead to unified treatments instead of managing them separately.","specificNumbers":"47 patients; 22 DS+, 25 DS-; glucose lower at 90 and 120 min (p<0.05); GLP-1 and PYY higher (p<0.05); hypoglycemia <3.3 mmol/L","methodology":"Cross-sectional observational study. 47 bariatric surgery patients completed a mixed meal test. Measured glucose, GLP-1, PYY, insulin, and symptom scores at multiple time points.","limitations":"Small sample (47 patients). Cross-sectional design cannot prove causation. No control group of non-surgical patients."},{"rthcId":"RPEP-05838","title":"Lipid-Polyglutamate Nanoparticle Vaccine Platform.","authors":"Van Lysebetten, Dorien; Malfanti, Alessio; Deswarte, Kim; Koynov, Kaloian; Golba, Bianka; Ye, Tingting; Zhong, Zifu; Kasmi, Sabah; Lamoot, Alexander; Chen, Yong; Van Herck, Simon; Lambrecht, Bart N; Sanders, Niek N; Lienenklaus, Stefan; David, Sunil A; Vicent, María J; De Koker, Stefaan; De Geest, Bruno G","year":2021,"journal":"ACS applied materials & interfaces, 13(5), 6011-6022","doi":"10.1021/acsami.0c20607","pmid":"33507728","tags":["peptide-vaccines","peptide-drug-delivery","cancer-and-oncology-peptides"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"PGA-based lipid nanoparticles co-delivering peptide antigen and TLR7/8 agonist activated antigen-specific T cells in mice via both subcutaneous and IV routes.","whyItMatters":"A universal platform for co-delivering any peptide antigen with immune boosters could accelerate personalized cancer vaccine development.","specificNumbers":"PGA-Ag + PGA-IMDQ co-delivered; ionizable lipid LNP; SC and IV routes; innate immune cell uptake confirmed; Ag-specific T cells induced","methodology":"Lab and animal study. Conjugated peptide antigen and IMDQ adjuvant to PGA. Condensed into lipid nanoparticles with ionizable lipid. Tested uptake by immune cells and T-cell activation in mouse models.","limitations":"Animal study in mice. Efficacy against actual tumors not tested. Human immune responses may differ. Specific peptide antigens tested were limited."},{"rthcId":"RPEP-05839","title":"Targeted deletion of PAC1 receptors in retinal neurons enhances neuron loss and axonopathy in a model of multiple sclerosis and optic neuritis.","authors":"Van, Christina; Condro, Michael C; Ko, Henly H; Hoang, Anh Q; Zhu, Ruoyan; Lov, Kenny; Ricaflanca, Patrick T; Diep, Anna L; Nguyen, Nhat N M; Lipshutz, Gerald S; MacKenzie-Graham, Allan; Waschek, James A","year":2021,"journal":"Neurobiology of disease, 160, 105524","doi":"10.1016/j.nbd.2021.105524","pmid":"34610465","tags":["pacap","neuroprotection","brain-and-cognition"],"studyType":"animal","evidenceStrength":"strong","keyFinding":"Neuronal PAC1 receptor deletion caused retinal neuron loss at baseline and increased neuron death and optic nerve damage in EAE, proving cell-autonomous neuroprotection by PACAP.","whyItMatters":"MS treatments control inflammation but do not stop neurons from dying. PACAP's direct neuron protection could fill this gap.","specificNumbers":"PAC1 deletion reduced RGN count at baseline; increased EAE neuron loss; increased optic nerve axonopathy; increased microglia/macrophage presence","methodology":"Animal study. Used AAV2 to deliver Cre recombinase to retinal neurons of floxed PAC1 mice. Subjected to EAE (MS model). Measured retinal ganglion cell counts, dendrites, optic nerve pathology, and microglia presence.","limitations":"Mouse model. EAE does not perfectly replicate human MS. Only retinal neurons were studied. Other neuron types may respond differently."},{"rthcId":"RPEP-05840","title":"LEAP-2/ghrelin interplay in adult growth hormone deficiency: Cause or consequence? A pilot study.","authors":"Vergani, Edoardo; Bruno, Carmine; Gavotti, Cesare; Aversa, Luigi Simone; Martire, Maria; Mancini, Antonio; Currò, Diego","year":2021,"journal":"IUBMB life, 73(7), 978-984","doi":"10.1002/iub.2504","pmid":"33991145","tags":["ghrelin","growth-hormone-axis","diabetes-and-metabolism"],"studyType":"observational","evidenceStrength":"low","keyFinding":"The LEAP-2/ghrelin ratio was significantly elevated in adult GH deficiency, with lower ghrelin levels possibly representing metabolic adaptation to prevent further weight gain.","whyItMatters":"Understanding how ghrelin and LEAP-2 interact in GH deficiency could reveal new treatment targets for metabolic complications of this condition.","specificNumbers":"30 subjects; ghrelin lower in aGHD (p significant); LEAP-2/ghrelin ratio higher (p significant); BMI-ghrelin inverse correlation r2=0.15, p=0.047","methodology":"Cross-sectional observational pilot study. 15 aGHD patients and 15 healthy controls. Measured fasting blood levels of ghrelin, LEAP-2, glucose, insulin, HOMA, cholesterol, triglycerides, and IGF-1.","limitations":"Very small pilot study (30 total). Cross-sectional design cannot determine cause and effect. BMI differed between groups, which could confound results."},{"rthcId":"RPEP-05841","title":"Challenges of peptide and protein drug delivery by oral route: Current strategies to improve the bioavailability.","authors":"Verma, Saurabh; Goand, Umesh K; Husain, Athar; Katekar, Roshan A; Garg, Richa; Gayen, Jiaur R","year":2021,"journal":"Drug development research, 82(7), 927-944","doi":"10.1002/ddr.21832","pmid":"33988872","tags":["peptide-drug-delivery","bioavailability-and-absorption","peptide-engineering"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"The review identifies three primary barriers to oral peptide/protein delivery:\n\n1. Acid degradation in the stomach (pH 1-2)\n2. Enzymatic degradation by proteases throughout the GI tract\n3. Poor cellular membrane permeability at the intestinal absorption site, plus first-pass hepatic metabolism\n\nCurrent strategies to overcome these barriers include:\n- Absorption enhancers and carriers to improve gut permeability\n- Structural modifications (cyclization, D-amino acid substitution, PEGylation) to improve stability\n- Advanced formulation technologies (nanoparticles, liposomes, microspheres)\n- Enzyme inhibitors to protect against proteolytic degradation\n- Enteric coatings to bypass stomach acid","whyItMatters":"Billions of people worldwide could benefit from peptide drugs for diabetes, obesity, osteoporosis, and other chronic conditions, but injections limit adoption. Oral delivery would dramatically improve patient compliance, reduce healthcare costs, and expand access to these therapies. The success of oral semaglutide demonstrates that this barrier can be overcome, motivating further research.","specificNumbers":"3 barriers: acid, enzymes, permeability; strategies: enhancers, modifications, nanoparticles, liposomes, advanced technologies","methodology":"This is a narrative review summarizing the current state of knowledge on oral peptide and protein drug delivery. It covers physicochemical factors affecting bioavailability, barriers in the GI tract, and technological approaches to improving oral absorption of peptide therapeutics.","limitations":"As a review article from 2021, it does not capture the most recent developments in oral peptide delivery. The field is evolving rapidly, and some approaches described may have been superseded. Many of the technologies reviewed are still in early development stages with limited clinical validation. The review provides a broad overview rather than a detailed comparison of approach effectiveness."},{"rthcId":"RPEP-05842","title":"Applying REWIND cardiovascular disease criteria to SUSTAIN 6 and PIONEER 6: An exploratory analysis of cardiovascular outcomes with semaglutide.","authors":"Verma, Subodh; Fainberg, Udi; Husain, Mansoor; Rasmussen, Søren; Rydén, Lars; Ripa, Maria Sejersten; Buse, John B","year":2021,"journal":"Diabetes, obesity & metabolism, 23(7), 1677-1680","doi":"10.1111/dom.14360","pmid":"33606902","tags":["glp-1","cardiovascular-health","diabetes-and-metabolism"],"studyType":"clinical-trial","evidenceStrength":"strong","keyFinding":"Semaglutide reduced MACE by 26% (HR 0.74) in patients with established CVD using REWIND criteria, with a non-significant 16% reduction in the risk factor subgroup (p-interaction=0.60).","whyItMatters":"This suggests semaglutide's heart protection is not limited to the highest-risk patients, potentially broadening who should receive it.","specificNumbers":"6,480 patients; established CVD HR 0.74 (0.59-0.92); risk factor HR 0.84 (0.55-1.28); p-interaction 0.60; 66.5% established CVD by REWIND criteria","methodology":"Post hoc pooled analysis of SUSTAIN 6 and PIONEER 6 trials (n=6,480). Re-categorized patients using REWIND cardiovascular disease criteria. Compared MACE outcomes.","limitations":"Post hoc analysis, not a prospective trial. Re-categorization changed group sizes. The risk factor subgroup result was not statistically significant."},{"rthcId":"RPEP-05843","title":"Cerebrolysin after moderate to severe traumatic brain injury: prospective meta-analysis of the CAPTAIN trial series.","authors":"Vester, Johannes C; Buzoianu, Anca D; Florian, Stefan I; Hömberg, Volker; Kim, Se-Hyuk; Lee, Tatia M C; Matula, Christian; Poon, Wai Sang; Sandesc, Dorel; von Steinbüchel, Nicole; Strilciuc, Stefan; Vos, Pieter E; von Wild, Klaus; Muresanu, Dafin","year":2021,"journal":"Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 42(11), 4531-4541","doi":"10.1007/s10072-020-04974-6","pmid":"33620612","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05844","title":"Current and future therapies for type 1 diabetes.","authors":"von Scholten, Bernt Johan; Kreiner, Frederik F; Gough, Stephen C L; von Herrath, Matthias","year":2021,"journal":"Diabetologia, 64(5), 1037-1048","doi":"10.1007/s00125-021-05398-3","pmid":"33595677","tags":["glp-1","diabetes-and-metabolism","peptide-vaccines","immune-system"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Beta cell rescue strategies including antigen vaccination, verapamil, and GLP-1 receptor agonists represent promising approaches alongside traditional immune modulation for type 1 diabetes.","whyItMatters":"Type 1 diabetes is increasing, especially in children. New approaches that protect remaining beta cells could reduce complications and dependence on insulin.","specificNumbers":"Strategies: oral insulin, peptide vaccination, verapamil, GLP-1 agonists; increasing incidence in children/adolescents; cardiometabolic complications increasingly recognized","methodology":"Narrative review of current and emerging prevention and treatment strategies for type 1 diabetes.","limitations":"This is a narrative review. Many discussed strategies are still experimental. No single approach has solved type 1 diabetes prevention."},{"rthcId":"RPEP-05845","title":"Acute endurance exercise stimulates circulating levels of mitochondrial-derived peptides in humans.","authors":"von Walden, Ferdinand; Fernandez-Gonzalo, Rodrigo; Norrbom, Jessica; Emanuelsson, Eric B; Figueiredo, Vandré C; Gidlund, Eva-Karin; Norrbrand, Lena; Liu, Chang; Sandström, Philip; Hansson, Björn; Wan, Junxiang; Cohen, Pinchas; Alkner, Björn","year":2021,"journal":"Journal of applied physiology (Bethesda, Md. : 1985), 131(3), 1035-1042","doi":"10.1152/japplphysiol.00706.2019","pmid":"34351816","tags":["humanin","mots-c","exercise-and-performance","aging-and-longevity"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"Acute endurance exercise significantly elevated circulating humanin but not MOTS-c, while resistance exercise changed neither. Baseline MDP levels correlated with age but not fitness.","whyItMatters":"MDPs are linked to aging and metabolic health. Finding that exercise stimulates them in humans could explain some of exercise's protective benefits.","specificNumbers":"30 subjects; 10 per group; 45 min cycling at 70% VO2max; 4x7RM leg exercises; humanin increased significantly after endurance; MOTS-c trended up; humanin correlated with age","methodology":"Randomized controlled study. 30 subjects split into endurance (n=10, 45 min cycling at 70% VO2max), resistance (n=10, 4 sets x 7RM), or control (n=10). Blood and muscle biopsies at baseline, 30 min, and 3 hours post-exercise.","limitations":"Small sample (10 per group). Single exercise bout. Did not test different exercise intensities or durations. MOTS-c trend did not reach significance."},{"rthcId":"RPEP-05846","title":"Optimized Adeno-Associated Virus Vectors for Efficient Transduction of Human Retinal Organoids.","authors":"Völkner, Manuela; Pavlou, Marina; Büning, Hildegard; Michalakis, Stylianos; Karl, Mike O","year":2021,"journal":"Human gene therapy, 32(13-14), 694-706","doi":"10.1089/hum.2020.321","pmid":"33752467","tags":["peptide-engineering","peptide-drug-delivery","clinical-applications"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"AAV9.NN with a surface peptide insert achieved fastest onset and highest transduction efficiency in human retinal organoids, detectable at 2 days post-transduction.","whyItMatters":"Better AAV vectors mean more effective gene therapy for inherited blindness conditions like retinitis pigmentosa.","specificNumbers":"AAV9.NN fastest onset at 2 days; dose-dependent; photoreceptors + interneurons + Muller glia; NN enhanced both AAV9 and AAV2","methodology":"Lab study. Transduced human iPSC-derived retinal organoids with AAV9, AAV9.GL, AAV9.NN, and AAV2.NN at increasing doses. Monitored eGFP expression over time. Assessed cell type tropism.","limitations":"Lab study in organoids, not in patients. Organoids may not perfectly replicate the adult human retina. Long-term expression not assessed."},{"rthcId":"RPEP-05847","title":"Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity: The STEP 3 Randomized Clinical Trial.","authors":"Wadden, Thomas A; Bailey, Timothy S; Billings, Liana K; Davies, Melanie; Frias, Juan P; Koroleva, Anna; Lingvay, Ildiko; O'Neil, Patrick M; Rubino, Domenica M; Skovgaard, Dorthe; Wallenstein, Signe O R; Garvey, W Timothy","year":2021,"journal":"JAMA, 325(14), 1403-1413","doi":"10.1001/jama.2021.1831","pmid":"33625476","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05848","title":"Chemical (neo)glycosylation of biological drugs.","authors":"Walther, Raoul; Zelikin, Alexander N","year":2021,"journal":"Advanced drug delivery reviews, 171, 62-76","doi":"10.1016/j.addr.2021.01.021","pmid":"33548302","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Chemical glycosylation improves proteolytic stability and reduces aggregation.","whyItMatters":"Enhancing the stability of biological drugs can lead to more effective treatments and better patient outcomes. This research could influence future drug development strategies.","specificNumbers":"","methodology":"The review analyzes existing literature and case studies on chemical glycosylation techniques.","limitations":"As a review, it does not present original experimental data and relies on existing studies, which may vary in quality."},{"rthcId":"RPEP-05849","title":"Peptide DR8 analogs alleviate pulmonary fibrosis via suppressing TGF-β1 mediated epithelial-mesenchymal transition and ERK1/2 pathway in vivo and in vitro.","authors":"Wang, Dan; Cheng, Lu; Li, Jieru; Deng, Bochuan; Yan, Tiantian; Yue, Xin; Zhang, Jianfeng; Zhang, Bangzhi; Xie, Junqiu","year":2021,"journal":"European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 167, 106009","doi":"10.1016/j.ejps.2021.106009","pmid":"34537373","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05850","title":"Deterministic chaos in the self-assembly of β sheet nanotubes from an amphipathic oligopeptide.","authors":"Wang, Fengbin; Gnewou, Ordy; Wang, Shengyuan; Osinski, Tomasz; Zuo, Xiaobing; Egelman, Edward H; Conticello, Vincent P","year":2021,"journal":"Matter, 4(10), 3217-3231","doi":"10.1016/j.matt.2021.06.037","pmid":"34632372","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Identified two forms of fibrils with four and five β sandwich protofilaments.","whyItMatters":"Understanding peptide self-assembly can lead to advancements in biomaterials and biomedical devices. It also provides insights into biological processes like amyloid formation.","specificNumbers":"","methodology":"The study utilized high-resolution cryoelectron microscopy to analyze the peptide structures.","limitations":"The study focuses on a specific octapeptide, which may limit the generalizability of the findings to other peptides."},{"rthcId":"RPEP-05851","title":"Self-assembly of photosensitive and radiotherapeutic peptide for combined photodynamic-radio cancer therapy with intracellular delivery of miRNA-139-5p.","authors":"Wang, Hanhua; Wang, Ziyi; Chen, Weiwei; Wang, Wencai; Shi, Woda; Chen, Jinzhong; Hang, Ye; Song, Jin; Xiao, Xiao; Dai, Zhenyu","year":2021,"journal":"Bioorganic & medicinal chemistry, 44, 116305","doi":"10.1016/j.bmc.2021.116305","pmid":"34273735","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Ce6-R9-125I-RGD-MNPs demonstrated superior tumor targeting and minimal toxicity to normal tissues.","whyItMatters":"This research could lead to more effective cancer treatments with fewer side effects, improving patient outcomes. It highlights the potential of combining therapies for better efficacy.","specificNumbers":"","methodology":"The researchers synthesized nanoparticles and tested their stability, targeting ability, and therapeutic effects in both lab and animal models.","limitations":"The study primarily focuses on in vitro and in vivo models, which may not fully translate to human patients."},{"rthcId":"RPEP-05852","title":"Long non-coding RNA NEAT1 functions as a competing endogenous RNA to regulate S100A9 expression by sponging miR-196a-5p in rosacea.","authors":"Wang, Lian; Wang, Yu-Jia; Hao, Dan; Wang, Xiao-Yun; Li, Xiao-Xue; Zhao, Qian; Li, Yan-Mei; He, Gu; Jiang, Xian","year":2021,"journal":"Journal of dermatological science, 102(1), 58-67","doi":"10.1016/j.jdermsci.2021.02.005","pmid":"33678493","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"RNA sequencing of skin from six rosacea patients identified 237 differentially expressed long non-coding RNAs, 38 miRNAs, and 1,784 mRNAs in lesioned vs. non-lesioned skin. NEAT1 was upregulated in both rosacea skin tissue and LL-37-treated HaCaT cells. Knocking down NEAT1 reduced inflammatory damage in vitro. NEAT1 directly interacted with miR-196a-5p, and downregulating miR-196a-5p reversed the anti-inflammatory effects of NEAT1 knockdown on S100A9, confirming the NEAT1/miR-196a-5p/S100A9 regulatory axis.","whyItMatters":"Rosacea affects millions of people and its molecular mechanisms are poorly understood, making treatment largely symptomatic. The cathelicidin peptide LL-37 has been identified as a key driver of rosacea inflammation, but how it triggers downstream inflammatory cascades was unclear. This study reveals a specific regulatory pathway (NEAT1/miR-196a-5p/S100A9) that connects LL-37 to sustained inflammation, providing potential new therapeutic targets that could interrupt the inflammatory cycle at its source.","specificNumbers":"","methodology":"Researchers performed genome-wide RNA sequencing on paired lesioned and non-lesioned skin samples from six rosacea patients, analyzing lncRNA, miRNA, and mRNA expression profiles. They identified hub lncRNAs in a competing endogenous RNA (ceRNA) network. In vitro experiments used HaCaT keratinocyte cells treated with the antimicrobial peptide LL-37 to model rosacea inflammation. Gene knockdown (siRNA) of NEAT1 and miR-196a-5p inhibitors were used to validate the regulatory axis.","limitations":"The genomic profiling used only six patients, limiting statistical power and generalizability. The in vitro experiments used HaCaT cells (an immortalized keratinocyte line), which may not fully replicate the behavior of primary skin cells or the complex multicellular environment of rosacea skin. The study demonstrates association and a plausible mechanism but does not prove this axis drives rosacea in vivo. No therapeutic intervention was tested in animal models or patients."},{"rthcId":"RPEP-05853","title":"Design of bovine lactoferricin-derived peptide and its expression and activity in Pichia pastoris.","authors":"Wang, Liang; Wang, Yu-Lian; Lv, Zi-Li; Zhang, En-Peng; Guo, Ai-Zhen","year":2021,"journal":"Biochemical and biophysical research communications, 534, 822-829","doi":"10.1016/j.bbrc.2020.10.098","pmid":"33239173","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The new peptide (LfcinBD) showed stronger antibacterial activity against Staphylococcus aureus than the original peptide.","whyItMatters":"This research could lead to the development of more effective antimicrobial treatments, addressing antibiotic resistance issues.","specificNumbers":"","methodology":"The study involved designing a peptide, cloning it into a plasmid, and expressing it in Pichia pastoris yeast cells.","limitations":"The study was conducted in vitro, and results may not directly translate to clinical applications in humans."},{"rthcId":"RPEP-05854","title":"Ultrashort Peptides and Hyaluronic Acid-Based Injectable Composite Hydrogels for Sustained Drug Release and Chronic Diabetic Wound Healing.","authors":"Wang, Ling; Li, Jing; Xiong, Yue; Wu, Yihang; Yang, Fen; Guo, Ying; Chen, Zhaolin; Gao, Liqian; Deng, Wenbin","year":2021,"journal":"ACS applied materials & interfaces, 13(49), 58329-58339","doi":"10.1021/acsami.1c16738","pmid":"34860513","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Diphenylalanine (FF) dipeptides modified with three different aromatic groups (benzene, naphthalene, pyrene) all formed composite hydrogels with hyaluronic acid (HA) featuring uniform distribution and good mechanical properties.\n\nThe naphthalene-modified version (N-FF/HA) showed the best performance: excellent self-healing properties (reforming after injection through a syringe), good biocompatibility with human skin fibroblast cells, and a structure of thinner nanofibers with honeycomb networks that enabled sustained curcumin release. In a streptozotocin-induced type I diabetic mouse model, curcumin-loaded N-FF/HA composite hydrogels promoted chronic wound healing significantly better than controls.","whyItMatters":"Diabetic foot ulcers and chronic wounds affect millions of patients worldwide and are a leading cause of amputations. Current wound care products often fail to provide sustained drug delivery in the challenging diabetic wound environment. This peptide-hyaluronic acid hydrogel addresses multiple challenges simultaneously: it's injectable (can fill irregular wound shapes), self-healing (maintains coverage), biocompatible, and provides sustained drug release. The ultrashort peptide design (just two amino acids) makes it potentially easy and inexpensive to manufacture.","specificNumbers":"","methodology":"Researchers synthesized diphenylalanine conjugated with benzene (B), naphthalene (N), and pyrene (P) aromatic moieties. These were combined with hyaluronic acid via a one-pot reaction to form composite hydrogels. The hydrogels were characterized for structure (nanofiber morphology), mechanical properties, self-healing ability, and biocompatibility using human skin fibroblast cells. Curcumin drug release kinetics were measured. In vivo wound healing was tested in a streptozotocin-induced type I diabetic mouse model.","limitations":"The study used a type I diabetic mouse model (streptozotocin-induced), which differs from the more common type II diabetes in humans. Specific wound closure rates, healing timepoints, and statistical comparisons were not detailed in the abstract. The curcumin drug loading and release kinetics were characterized but specific values were not reported. Long-term safety and degradation products were not assessed. Human clinical translation requires further validation."},{"rthcId":"RPEP-05855","title":"Thymosin β4 reverses phenotypic polarization of glial cells and cognitive impairment via negative regulation of NF-κB signaling axis in APP/PS1 mice.","authors":"Wang, Meng; Feng, Li-Rong; Li, Zi-Long; Ma, Kai-Ge; Chang, Ke-Wei; Chen, Xin-Lin; Yang, Peng-Bo; Ji, Sheng-Feng; Ma, Yan-Bing; Han, Hua; Ruganzua, John Bosco; Yang, Wei-Na; Qian, Yi-Hua","year":2021,"journal":"Journal of neuroinflammation, 18(1), 146","doi":"10.1186/s12974-021-02166-3","pmid":"34183019","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tβ4 reduced brain Aβ accumulation and improved cognitive performance in APP/PS1 mice.","whyItMatters":"These findings could lead to new therapeutic strategies for Alzheimer's disease by targeting inflammation and cognitive decline.","specificNumbers":"","methodology":"The study involved behavioral tests and various laboratory techniques to assess brain changes in APP/PS1 mice after Tβ4 treatment.","limitations":"The study was conducted in mice, and results may not directly translate to humans; further research is needed to confirm efficacy and safety in humans."},{"rthcId":"RPEP-05856","title":"Building Personalized Cancer Therapeutics through Multi-Omics Assays and Bacteriophage-Eukaryotic Cell Interactions.","authors":"Wang, Qing","year":2021,"journal":"International journal of molecular sciences, 22(18)","doi":"10.3390/ijms22189712","pmid":"34575870","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Developed the first antibody-based neoantigen targeting approach for personalized cancer therapeutics.","whyItMatters":"This research could significantly enhance the effectiveness of cancer immunotherapies by personalizing treatment based on individual tumor markers.","specificNumbers":"","methodology":"The study utilized phage display technology to identify neoantigens and create targeted therapeutics.","limitations":"The study primarily discusses methodologies and theoretical applications without extensive clinical trial data."},{"rthcId":"RPEP-05857","title":"Neurokinin-1-tachykinin receptor agonist promotes diabetic fracture healing in rats with type 1 diabetes via modulation of Wnt/β-catenin signalling axis.","authors":"Wang, Xiaohui; Su, Ning","year":2021,"journal":"Saudi journal of biological sciences, 28(4), 2139-2145","doi":"10.1016/j.sjbs.2021.02.026","pmid":"33911930","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Substance P (50 mg/ml/kg, intraperitoneal) administered before fracture surgery in type 1 diabetic rats promoted bone healing through multiple measured effects: upregulation of osteogenic markers RUNX2, osterix (OSTX), and osteocalcin (OSTC); optimization of the bone resorption axis with favorable OPG/RANKL/RANK balance; and activation of the Wnt/β-catenin signaling pathway manifested by upregulated β-catenin and LRP5 with downregulated GSK-3β.\n\nCritically, local delivery of the Wnt antagonist DKK1 (via adenovirus) at the fracture site reversed substance P's beneficial effects, confirming that the Wnt/β-catenin pathway is the essential mediator. Radiographic assessment showed reduced gap size in substance P-treated diabetic fractures compared to untreated diabetic fractures.","whyItMatters":"Diabetic patients experience fracture healing rates 2-3 times slower than non-diabetic patients, with higher rates of non-union and complications. Current treatments are limited to standard fracture care with no approved therapies specifically targeting the diabetic healing deficit. If substance P or NK1R agonists can restore normal bone healing in diabetic patients, it would address a major unmet clinical need affecting millions of people worldwide with diabetes-related fractures.","specificNumbers":"","methodology":"Type 1 diabetes was induced in rats using streptozotocin (50 mg/kg for 5 consecutive days). Rats were divided into four groups: non-diabetic fractured controls, diabetic fractured (untreated), diabetic fractured + substance P, and diabetic fractured + substance P + DKK1 (Wnt inhibitor delivered via recombinant adenovirus at the fracture site). Bone healing was assessed by radiographic gap measurement. Protein expression of osteogenic markers (RUNX2, OSTX, OSTC), bone resorption markers (OPG, RANKL, RANK), and Wnt pathway markers (β-catenin, LRP5, GSK-3β) was determined by Western blot.","limitations":"The study was conducted in rats with chemically induced type 1 diabetes, which may not fully replicate human diabetic bone disease. The substance P dose (50 mg/ml/kg) is very high for in vivo administration, and dose optimization studies were not reported. Only short-term molecular markers were assessed — long-term functional bone strength and complete healing outcomes were not reported. The DKK1 was delivered via adenovirus, which has its own inflammatory effects that could confound results. Type 2 diabetes, which is far more common, was not studied."},{"rthcId":"RPEP-05858","title":"Efficacy and Safety of Monoclonal Antibody Against Calcitonin Gene-Related Peptide or Its Receptor for Migraine: A Systematic Review and Network Meta-analysis.","authors":"Wang, Xing; Chen, Yuqi; Song, Jinlei; You, Chao","year":2021,"journal":"Frontiers in pharmacology, 12, 649143","doi":"10.3389/fphar.2021.649143","pmid":"33867991","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"All four CGRP monoclonal antibodies significantly reduced monthly migraine days (MMDs) compared to placebo: eptinezumab (MD -1.43 days), erenumab (MD -1.61 days), fremanezumab (MD -2.19 days), and galcanezumab (MD -2.10 days).\n\nRegarding safety, only galcanezumab showed significantly increased treatment-emergent adverse events (RR 1.11, 95% CrI 1.01–1.22) and serious adverse events (RR 2.95, 95% CrI 1.41–6.87) compared to placebo. The other three antibodies had adverse event rates comparable to placebo. Overall, the drugs performed similarly to each other across most analyses.","whyItMatters":"With four CGRP antibodies available, clinicians and patients need to know which one to choose. This network meta-analysis provides the most comprehensive indirect comparison to date, revealing that while all four are effective, they differ meaningfully in safety profiles. The finding that galcanezumab alone was associated with more adverse events — including serious ones — is clinically significant information for prescribing decisions.","specificNumbers":"","methodology":"This was a systematic review and network meta-analysis of 18 randomized controlled trials (n=8,926) identified from MEDLINE, Embase, ClinicalTrials.gov, and Cochrane Library databases through October 2020. Network meta-analysis allows indirect comparison between drugs that haven't been tested head-to-head by using placebo as a common comparator. Primary outcomes were changes in monthly migraine days and treatment-emergent adverse events.","limitations":"Network meta-analysis relies on indirect comparisons, which are less reliable than head-to-head trials. The included trials varied in design, patient populations, dosing regimens, and follow-up durations. The safety signal for galcanezumab could reflect differences in trial design or patient selection rather than true drug-specific risks. Data was limited to publications through October 2020, so more recent evidence is not captured. The analysis does not distinguish between episodic and chronic migraine subgroups in detail."},{"rthcId":"RPEP-05859","title":"A first-in-human, randomized, double-blind, single- and multiple-dose, phase I study of recombinant human thymosin β4 in healthy Chinese volunteers.","authors":"Wang, Xinghe; Liu, Long; Qi, Lu; Lei, Chunpu; Li, Pu; Wang, Yu; Liu, Chen; Bai, Haihong; Han, Chengquan; Sun, Yinjian; Liu, Jincan","year":2021,"journal":"Journal of cellular and molecular medicine, 25(17), 8222-8228","doi":"10.1111/jcmm.16693","pmid":"34346165","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Thymosin β4 was well tolerated with no serious adverse events reported across doses.","whyItMatters":"Understanding the safety of thymosin β4 is crucial for its potential use in treating serious conditions like heart attacks. This study lays the groundwork for future research.","specificNumbers":"","methodology":"The study involved a randomized, double-blind design with healthy volunteers receiving single and multiple doses of thymosin β4.","limitations":"The study was limited to healthy volunteers, and results may not apply to patients with specific conditions."},{"rthcId":"RPEP-05860","title":"The RNA helicase Dhx15 mediates Wnt-induced antimicrobial protein expression in Paneth cells.","authors":"Wang, Yalong; He, Kaixin; Sheng, Baifa; Lei, Xuqiu; Tao, Wanyin; Zhu, Xiaoliang; Wei, Zheng; Fu, Rongjie; Wang, Anlei; Bai, Shengdan; Zhang, Zhao; Hong, Na; Ye, Chao; Tian, Ye; Wang, Jun; Li, Mingsong; Zhang, Kaiguang; Li, Lin; Yang, Hua; Li, Hua-Bing; Flavell, Richard A; Zhu, Shu","year":2021,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 118(4)","doi":"10.1073/pnas.2017432118","pmid":"33483420","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Mice lacking Dhx15 in intestinal cells showed increased susceptibility to Citrobacter rodentium infection and colitis.","whyItMatters":"Understanding the role of Dhx15 could lead to new insights into gut health and treatments for inflammatory bowel diseases like ulcerative colitis.","specificNumbers":"","methodology":"The study involved generating genetically modified mice with specific deletions of Dhx15 in intestinal epithelial cells and Paneth cells to assess their immune responses.","limitations":"The study primarily used mouse models, which may not fully replicate human conditions."},{"rthcId":"RPEP-05861","title":"Identification and characterization of novel bi-functional cathelicidins from the black-spotted frog (Pelophylax nigromaculata) with both anti-infective and antioxidant activities.","authors":"Wang, Yan; Ouyang, Jianhong; Luo, Xuanjin; Zhang, Minghui; Jiang, Yu; Zhang, Fen; Zhou, Jiang; Wang, Yipeng","year":2021,"journal":"Developmental and comparative immunology, 116, 103928","doi":"10.1016/j.dci.2020.103928","pmid":"33242568","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"PN-CATHs showed broad-spectrum antimicrobial activity and potent antioxidant effects.","whyItMatters":"Discovering new antimicrobial peptides can lead to the development of effective treatments for infections, especially those resistant to current antibiotics.","specificNumbers":"","methodology":"The study involved identifying and characterizing new cathelicidins from frog skin, assessing their antimicrobial and antioxidant activities in vitro.","limitations":"The study primarily focuses on in vitro results, and further research is needed to confirm efficacy in vivo and in humans."},{"rthcId":"RPEP-05862","title":"Amino Acid Sequences of Lactoferrin from Red Deer (Cervus elaphus) Milk and Antimicrobial Activity of Its Derived Peptides Lactoferricin and Lactoferrampin.","authors":"Wang, Ye; Morton, James D; Bekhit, Alaa El-Din A; Carne, Alan; Mason, Susan L","year":2021,"journal":"Foods (Basel, Switzerland), 10(6)","doi":"10.3390/foods10061305","pmid":"34200201","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Deer lactoferricin was more effective against L. acidophilus than bovine lactoferricin, while bovine peptides were more effective against E. coli.","whyItMatters":"Understanding the antimicrobial properties of deer lactoferrin could lead to new applications in food safety and health. This research adds to the knowledge of lactoferrin's bioactivity across different species.","specificNumbers":"","methodology":"The study involved sequencing the lactoferrin from deer milk and testing the antimicrobial activity of its derived peptides against specific bacterial strains.","limitations":"The study focused only on specific bacterial strains and may not represent broader antimicrobial effectiveness."},{"rthcId":"RPEP-05863","title":"Thymosin β4 released from functionalized self-assembling peptide activates epicardium and enhances repair of infarcted myocardium.","authors":"Wang, Yong-Li; Yu, Shu-Na; Shen, Hao-Ran; Wang, Hai-Jie; Wu, Xue-Ping; Wang, Qiang-Li; Zhou, Bin; Tan, Yu-Zhen","year":2021,"journal":"Theranostics, 11(9), 4262-4280","doi":"10.7150/thno.52309","pmid":"33754060","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tβ4 released from the peptide enhanced heart repair, improved cardiac function, and promoted angiogenesis and lymphangiogenesis.","whyItMatters":"This research suggests a new therapeutic approach for heart attack recovery, potentially improving patient outcomes. Activating the epicardium could lead to better heart regeneration strategies.","specificNumbers":"","methodology":"Transgenic mice with myocardial infarction were treated with Tβ4-conjugated self-assembling peptide, and heart tissue was analyzed for cell migration and differentiation.","limitations":"The study was conducted in transgenic mice, and results may not directly translate to human patients. Long-term effects and safety need further investigation."},{"rthcId":"RPEP-05864","title":"Molecular recognition of an acyl-peptide hormone and activation of ghrelin receptor.","authors":"Wang, Yue; Guo, Shimeng; Zhuang, Youwen; Yun, Ying; Xu, Peiyu; He, Xinheng; Guo, Jia; Yin, Wanchao; Xu, H Eric; Xie, Xin; Jiang, Yi","year":2021,"journal":"Nature communications, 12(1), 5064","doi":"10.1038/s41467-021-25364-2","pmid":"34417468","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The study identified a unique binding pocket for the octanoyl group of ghrelin, essential for receptor activation.","whyItMatters":"Understanding how ghrelin activates its receptor can lead to new treatments for obesity and metabolic disorders. This research provides a foundation for drug design targeting the ghrelin receptor.","specificNumbers":"","methodology":"Cryo-electron microscopy was used to determine the structures of the ghrelin receptor bound to ghrelin and GHRP-6.","limitations":"The study primarily focuses on structural analysis and does not include in vivo testing of the findings."},{"rthcId":"RPEP-05865","title":"Adjunctive Thymosin Beta-4 Treatment Influences PMN Effector Cell Function during Pseudomonas aeruginosa-Induced Corneal Infection.","authors":"Wang, Yuxin; Carion, Thomas W; Ebrahim, Abdul Shukkur; Sosne, Gabriel; Berger, Elizabeth A","year":2021,"journal":"Cells, 10(12)","doi":"10.3390/cells10123579","pmid":"34944086","tags":[],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Adding thymosin beta-4 (Tβ4) to ciprofloxacin antibiotic treatment significantly improved outcomes in bacterial eye infections in mice. The combination reduced the number of neutrophils (PMNs) infiltrating infected corneas and downregulated pro-inflammatory markers on those cells. Tβ4 also promoted well-regulated production of reactive oxygen species (ROS) and neutrophil extracellular traps (NETs), with limited neutrophil death (apoptosis).\n\nThe study confirmed both in vivo and in vitro that Tβ4 modulates how neutrophils respond to infection — not by suppressing immunity, but by regulating it. An additional finding was that neutrophil elastase (NE) was unnecessary for NET formation (NETosis), challenging previous assumptions about how NETs are generated.","whyItMatters":"Bacterial keratitis (corneal infection) can cause vision loss, and while antibiotics kill the bacteria, the inflammatory damage from the immune response itself often causes much of the tissue destruction. Thymosin beta-4 addresses this dual problem — it works synergistically with antibiotics to fight infection while simultaneously preventing excessive immune-mediated tissue damage. This two-pronged approach could preserve more corneal tissue and improve visual outcomes.","specificNumbers":"P. aeruginosa infection model · C57BL/6 mice · Significant reduction in PMN infiltration with Tβ4 + ciprofloxacin · Downregulated proinflammatory markers · Well-regulated ROS and NET production · Confirmed in vivo and in vitro","methodology":"Researchers infected C57BL/6 mouse corneas with Pseudomonas aeruginosa bacteria and treated them with ciprofloxacin alone or ciprofloxacin plus Tβ4. Flow cytometry was used to profile infiltrating neutrophils. ROS production, NET formation, and neutrophil apoptosis were measured. In vitro experiments using peritoneal-derived neutrophils were conducted to verify and extend the in vivo results.","limitations":"This is a mouse study and results may not directly translate to human corneal infections. The abstract does not report specific sample sizes per group, quantitative ROS/NET reduction values, or visual outcome measures. The P. aeruginosa model represents one type of bacterial keratitis; efficacy against other pathogens is unknown."},{"rthcId":"RPEP-05866","title":"Adjunctive Thymosin Beta-4 Treatment Influences MΦ Effector Cell Function to Improve Disease Outcome in Pseudomonas aeruginosa-Induced Keratitis.","authors":"Wang, Yuxin; Carion, Thomas W; Ebrahim, Abdul Shukkur; Sosne, Gabriel; Berger, Elizabeth A","year":2021,"journal":"International journal of molecular sciences, 22(20)","doi":"10.3390/ijms222011016","pmid":"34681676","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tβ4 treatment significantly reduced reactive nitrogen species production and macrophage infiltration.","whyItMatters":"Improving treatments for bacterial keratitis can enhance patient outcomes and reduce complications. Understanding macrophage behavior can inform future therapies.","specificNumbers":"","methodology":"The study used flow cytometry to analyze macrophage function and in vitro experiments with RAW 264.7 cells to confirm findings.","limitations":"The study primarily used an experimental model, which may not fully replicate human responses."},{"rthcId":"RPEP-05867","title":"Thymosin Alpha-1 Has no Beneficial Effect on Restoring CD4+ and CD8+ T Lymphocyte Counts in COVID-19 Patients.","authors":"Wang, Zhenyan; Chen, Jun; Zhu, Cuiyun; Liu, Li; Qi, Tangkai; Shen, Yinzhong; Zhang, Yuyi; Xu, Lie; Li, Tao; Qian, Zhiping; Steinhart, Corklin R; Lu, Hongzhou","year":2021,"journal":"Frontiers in immunology, 12, 568789","doi":"10.3389/fimmu.2021.568789","pmid":"34149679","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 275 COVID-19 patients (126 receiving Tα1, 149 not), there was no significant difference in CD4+ T cell recovery (286 vs. 326, p=0.851) or CD8+ T cell recovery (154 vs. 170, p=0.842) during the recovery period.\n\nNotably, in patients with decreased baseline CD4 counts and in the severe illness subgroup, virus clearance duration was significantly longer in the Tα1-treated group. Multivariate regression analysis confirmed that both illness severity (p<0.001) and Tα1 therapy (p=0.001) were independently associated with virus clearance time — with Tα1 therapy associated with longer clearance.","whyItMatters":"Thymosin alpha-1 has been widely used in Asia as an immune-boosting peptide for infections and cancer. During the pandemic, it was administered to many COVID-19 patients based on its reputation for immune restoration. This study provides important negative evidence that challenges the assumed benefit, highlighting the critical need for controlled trials before adopting peptide therapies based on mechanism-of-action reasoning alone.","specificNumbers":"","methodology":"Retrospective cohort study of 275 COVID-19 patients admitted to Shanghai Public Health Clinical Center. Patients were divided into Tα1-treated (n=126) and untreated (n=149) groups. Longitudinal T lymphocyte subset counts (CD4+ and CD8+) were compared between groups. Clinical outcomes including virus clearance duration were assessed. Multivariate linear regression controlled for confounders including illness severity.","limitations":"This is a retrospective study, so patients receiving Tα1 may have been sicker at baseline (confounding by indication). The study was not randomized, limiting the ability to draw causal conclusions. The Tα1 dose, timing, and duration varied. Virus clearance was measured by PCR, which may not reflect clinical outcomes. Only T cell counts were assessed — other immune parameters that Tα1 might affect were not evaluated."},{"rthcId":"RPEP-05868","title":"Conditional ablation of vasopressin-synthesizing neurons in transgenic rats.","authors":"Watanabe, Jun; Takayanagi, Yuki; Yoshida, Masahide; Hattori, Tatsuya; Saito, Michiko; Kohno, Kenji; Kobayashi, Eiji; Onaka, Tatsushi","year":2021,"journal":"Journal of neuroendocrinology, 33(12), e13057","doi":"10.1111/jne.13057","pmid":"34748241","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Researchers successfully created transgenic rats where vasopressin-producing neurons in specific brain regions (PVN and SON) could be selectively destroyed using diphtheria toxin. When these neurons were ablated, rats developed excessive thirst and urination — symptoms that were rescued by administering the vasopressin analog DDAVP (desmopressin) via an osmotic mini-pump.\n\nImportantly, the technique selectively targeted vasopressin neurons without affecting neighboring oxytocin-producing neurons, and neurons in the suprachiasmatic nucleus (SCN) were spared, demonstrating regional specificity.","whyItMatters":"Vasopressin is a peptide hormone with roles in water balance, social behavior, stress responses, and circadian rhythms, but studying each function has been difficult because vasopressin neurons exist in multiple brain regions. This new tool allows researchers to selectively eliminate vasopressin neurons in specific areas, enabling precise study of what each group of neurons does — a critical advance for understanding this peptide's diverse functions.","specificNumbers":"3 brain regions with vasopressin neurons (PVN, SON, SCN) · PVN and SON neurons successfully ablated · SCN neurons spared · Oxytocin neurons unaffected · DDAVP rescue confirmed","methodology":"Researchers created transgenic rats expressing a mutated human diphtheria toxin receptor controlled by the vasopressin gene promoter. After salt loading (to activate vasopressin gene expression in PVN and SON), they administered diphtheria toxin via intracerebroventricular injection. They then measured vasopressin and oxytocin neuron counts via immunohistochemistry and assessed water intake and urine output.","limitations":"This is a transgenic rat model, so findings may not directly apply to humans. The ablation technique requires salt loading to activate vasopressin neurons in specific regions before toxin administration, limiting spontaneous use. The study focused on validating the tool rather than comprehensively mapping vasopressin's behavioral functions, which remain to be studied using this model."},{"rthcId":"RPEP-05869","title":"Structures suggest an approach for converting weak self-peptide tumor antigens into superagonists for CD8 T cells in cancer.","authors":"Wei, Pengcheng; Jordan, Kimberly R; Buhrman, Jonathan D; Lei, Jun; Deng, Hexiang; Marrack, Philippa; Dai, Shaodong; Kappler, John W; Slansky, Jill E; Yin, Lei","year":2021,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 118(23)","doi":"10.1073/pnas.2100588118","pmid":"34074778","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A single amino acid substitution in a weak self-tumor antigen increased TCR affinity and immune response.","whyItMatters":"This research provides a potential strategy for improving cancer vaccines, which could lead to better treatment options for patients. By enhancing the immune response to self-tumor antigens, it may be possible to develop more effective immunotherapies.","specificNumbers":"","methodology":"The study involved structural analysis and immunological testing of modified and unmodified self-tumor antigens in murine models.","limitations":"The study was conducted in murine models, which may not fully translate to human responses. Further research is needed to confirm these findings in clinical settings."},{"rthcId":"RPEP-05870","title":"Comparison of the effects of 10 GLP-1 RA and SGLT2 inhibitor interventions on cardiovascular, mortality, and kidney outcomes in type 2 diabetes: A network meta-analysis of large randomized trials.","authors":"Wei, Xu-Bin; Wei, Wei; Ding, Liang-Liang; Liu, Shu-Yan","year":2021,"journal":"Primary care diabetes, 15(2), 208-211","doi":"10.1016/j.pcd.2020.08.017","pmid":"32912710","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Subcutaneous semaglutide and albiglutide significantly reduced major adverse cardiovascular events compared to lixisenatide.","whyItMatters":"Understanding which diabetes medications are most effective for heart and kidney health can guide treatment decisions and improve patient outcomes. This research helps clarify the benefits of different drug classes for managing type 2 diabetes.","specificNumbers":"","methodology":"A Bayesian network meta-analysis was conducted using data from randomized trials, focusing on major adverse cardiovascular events, heart failure hospitalizations, and kidney function progression.","limitations":"The study relies on existing trial data, which may introduce bias and limit the generalizability of findings."},{"rthcId":"RPEP-05871","title":"Elamipretide (SS-31) treatment attenuates age-associated post-translational modifications of heart proteins.","authors":"Whitson, Jeremy A; Martín-Pérez, Miguel; Zhang, Tong; Gaffrey, Matthew J; Merrihew, Gennifer E; Huang, Eric; White, Collin C; Kavanagh, Terrance J; Qian, Wei-Jun; Campbell, Matthew D; MacCoss, Michael J; Marcinek, David J; Villén, Judit; Rabinovitch, Peter S","year":2021,"journal":"GeroScience, 43(5), 2395-2412","doi":"10.1007/s11357-021-00447-6","pmid":"34480713","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Elamipretide treatment for 8 weeks almost completely reversed age-related increases in S-glutathionylation in mouse hearts.","whyItMatters":"Understanding how elamipretide reverses age-related changes in heart proteins could lead to new therapies for age-associated heart diseases. This research highlights potential interventions to improve heart health in older adults.","specificNumbers":"","methodology":"The study used shotgun proteomics to analyze the S-glutathionylation and phosphorylation of heart proteins in young and old mice, comparing the effects of elamipretide treatment.","limitations":"The study was conducted in mice, so results may not directly translate to humans. Further research is needed to explore long-term effects and safety in humans."},{"rthcId":"RPEP-05872","title":"Glucagon-like Peptide-1 Receptor as Emerging Target: Will It Make It to the Clinic?","authors":"Wild, Damian; Antwi, Kwadwo; Fani, Melpomeni; Christ, Emanuel R","year":2021,"journal":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 62(Suppl 2), 44S-50S","doi":"10.2967/jnumed.120.246009","pmid":"34230073","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1R PET/CT is significantly more sensitive than ceMRI and ceCT for detecting benign insulinomas.","whyItMatters":"This research could lead to improved diagnostic techniques for insulinomas, which are often difficult to detect. Enhanced imaging may allow for better treatment planning and outcomes for patients.","specificNumbers":"","methodology":"The study involved evaluating various radiopharmaceuticals for GLP-1R PET/CT imaging and comparing their effectiveness against traditional imaging methods.","limitations":"The study primarily focuses on imaging techniques and does not address treatment outcomes or long-term patient follow-up."},{"rthcId":"RPEP-05873","title":"Once-Weekly Semaglutide in Adults with Overweight or Obesity.","authors":"Wilding, John P H; Batterham, Rachel L; Calanna, Salvatore; Davies, Melanie; Van Gaal, Luc F; Lingvay, Ildiko; McGowan, Barbara M; Rosenstock, Julio; Tran, Marie T D; Wadden, Thomas A; Wharton, Sean; Yokote, Koutaro; Zeuthen, Niels; Kushner, Robert F","year":2021,"journal":"The New England journal of medicine, 384(11), 989-1002","doi":"10.1056/NEJMoa2032183","pmid":"33567185","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05874","title":"Peptide Hydrogel Scaffold for Mesenchymal Precursor Cells Implanted to Injured Adult Rat Spinal Cord.","authors":"Wiseman, Tylie M; Baron-Heeris, Danii; Houwers, Imke G J; Keenan, Rory; Williams, Richard J; Nisbet, David R; Harvey, Alan R; Hodgetts, Stuart I","year":2021,"journal":"Tissue engineering. Part A, 27(15-16), 993-1007","doi":"10.1089/ten.TEA.2020.0115","pmid":"33040713","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The hydrogel reduced cyst size significantly compared to SCI-only controls, but functional improvement was inconsistent.","whyItMatters":"Understanding how to support spinal cord repair can lead to better treatments for injuries in humans. This research highlights the potential of peptide hydrogels in regenerative medicine.","specificNumbers":"","methodology":"Adult Fischer 344 rats with spinal cord injury received treatments of the peptide hydrogel alone, with viable or nonviable cells, or no treatment. Behavioral assessments and tissue analysis were conducted after 8 weeks.","limitations":"The study was conducted in rats, which may limit the applicability of results to humans. Additionally, the functional improvements were not consistently observed across all treatment groups."},{"rthcId":"RPEP-05875","title":"Genetic variation in neuropeptide Y interacts with childhood trauma to influence anxiety sensitivity.","authors":"Womersley, Jacqueline Samantha; Martin, Lindi; van der Merwe, Lize; Seedat, Soraya; Hemmings, Sian Megan Joanna","year":2021,"journal":"Anxiety, stress, and coping, 34(4), 450-464","doi":"10.1080/10615806.2021.1876225","pmid":"33491492","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In Xhosa females, the NPY rs5573 A allele increased anxiety sensitivity (p=0.035), while the rs3037354 deletion variant decreased it (p=0.034).","whyItMatters":"Understanding how genetic and environmental factors interact can help identify individuals at risk for anxiety disorders. This research emphasizes the importance of considering diverse populations in psychiatric genetics.","specificNumbers":"","methodology":"The study used a cross-sectional design to analyze genetic variants and their interaction with childhood trauma in a sample of 951 adolescents.","limitations":"The study's cross-sectional design limits causal inferences, and the findings may not generalize beyond the specific ethnic groups studied."},{"rthcId":"RPEP-05876","title":"Casomorphins and Gliadorphins Have Diverse Systemic Effects Spanning Gut, Brain and Internal Organs.","authors":"Woodford, Keith Bernard","year":2021,"journal":"International journal of environmental research and public health, 18(15)","doi":"10.3390/ijerph18157911","pmid":"34360205","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05877","title":"Mitochondrial-derived peptides and exercise.","authors":"Woodhead, Jonathan S T; Merry, Troy L","year":2021,"journal":"Biochimica et biophysica acta. General subjects, 1865(12), 130011","doi":"10.1016/j.bbagen.2021.130011","pmid":"34520826","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Acute high-intensity exercise increases concentrations of the mitochondrial-derived peptides (MDPs) humanin and MOTS-c in human skeletal muscle and plasma. MOTS-c treatment in mice improved exercise capacity and performance in both young and aged animals, producing adaptations similar to physical activity — including weight loss, increased antioxidant capacity, and improved insulin sensitivity. However, studies using a MOTS-c inactivating genetic variant and combination exercise + MOTS-c treatment suggest distinct and overlapping pathways between exercise and MOTS-c benefits. Evidence for chronic training effects on MDP expression is conflicting and appears to depend on exercise mode, duration, intensity, and participant characteristics.","whyItMatters":"This review reveals that mitochondria communicate their status during exercise stress by releasing small peptides encoded in mitochondrial DNA — a newly recognized signaling mechanism. The finding that MOTS-c can mimic some exercise benefits in mice (including in aged animals) raises the possibility of developing peptide-based therapies that could provide exercise-like metabolic benefits for people who cannot exercise due to age, disability, or illness.","specificNumbers":"2 key MDPs studied (humanin, MOTS-c) · Benefits in both young and aged mice · Weight loss + antioxidant capacity + insulin sensitivity with MOTS-c · Distinct + overlapping pathways with exercise","methodology":"Narrative review synthesizing evidence from human exercise studies (acute and chronic) and mouse models examining the effects of exercise on mitochondrial-derived peptide expression and the effects of exogenous MOTS-c treatment on exercise capacity and metabolic parameters.","limitations":"This is a review article, not a primary study. The evidence for chronic training effects on MDPs is conflicting. Most MOTS-c treatment studies are in mice, and human clinical data is limited. The review notes that MDPs beyond MOTS-c have not been well-studied for exercise-mimetic properties, leaving much of the landscape unexplored."},{"rthcId":"RPEP-05878","title":"Cell penetrating peptide TAT-functionalized liposomes for efficient ophthalmic delivery of flurbiprofen: Penetration and its underlying mechanism, retention, anti-inflammation and biocompatibility.","authors":"Wu, Baohuan; Li, Mengshun; Li, Keke; Hong, Wei; Lv, Qingzhi; Li, Youjie; Xie, Shuyang; Han, Jingtian; Tian, Baocheng","year":2021,"journal":"International journal of pharmaceutics, 598, 120405","doi":"10.1016/j.ijpharm.2021.120405","pmid":"33647409","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"TAT-Lip significantly reduced drug loss rate and enhanced anti-inflammatory effects.","whyItMatters":"Improving drug delivery to the eye can enhance treatment outcomes for various ocular diseases. This research could lead to better therapies with fewer side effects.","specificNumbers":"","methodology":"The study used in vitro assays and in vivo pharmacokinetics assessments in rabbits to evaluate the effectiveness of TAT-functionalized liposomes.","limitations":"The study primarily used animal models, which may not fully predict human responses."},{"rthcId":"RPEP-05879","title":"FM-CATH, A Novel Cathelicidin From Fejervarya Multistriata, Shows Therapeutic Potential for Treatment of CLP-Induced Sepsis.","authors":"Wu, Jiena; Zhang, Haiyun; Chen, Xiaoxin; Chai, Jinwei; Hu, Yunrui; Xiong, Weichen; Lu, Wancheng; Tian, Maolin; Chen, Xin; Xu, Xueqing","year":2021,"journal":"Frontiers in pharmacology, 12, 731056","doi":"10.3389/fphar.2021.731056","pmid":"34483941","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"FM-CATH improved survival rates and reduced bacterial counts in sepsis mice models.","whyItMatters":"Sepsis is a life-threatening condition with limited treatment options. Discovering new agents like FM-CATH could enhance therapeutic strategies.","specificNumbers":"","methodology":"The study involved characterizing FM-CATH, assessing its antimicrobial effects, and testing its impact on sepsis in mice.","limitations":"The study was conducted in mice, and results may not directly translate to humans."},{"rthcId":"RPEP-05880","title":"Scorpion Venom Heat-Resistant Peptide Attenuates Microglia Activation and Neuroinflammation.","authors":"Wu, Xue-Fei; Li, Chun; Yang, Guang; Wang, Ying-Zi; Peng, Yan; Zhu, Dan-Dan; Sui, Ao-Ran; Wu, Qiong; Li, Qi-Fa; Wang, Bin; Li, Na; Zhang, Yue; Ge, Bi-Ying; Zhao, Jie; Li, Shao","year":2021,"journal":"Frontiers in pharmacology, 12, 704715","doi":"10.3389/fphar.2021.704715","pmid":"34675802","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"SVHRP treatment significantly reduced iNOS and TNF-α levels in LPS-injected mice and cell cultures.","whyItMatters":"Understanding how SVHRP works could lead to new treatments for neuroinflammatory conditions, which are linked to various brain disorders.","specificNumbers":"","methodology":"The study used an animal model with LPS-induced neuroinflammation and primary brain cell cultures to assess the effects of SVHRP on inflammatory markers.","limitations":"The study was conducted in animal models, which may not fully replicate human responses."},{"rthcId":"RPEP-05881","title":"Stapled Wasp Venom-Derived Oncolytic Peptides with Side Chains Induce Rapid Membrane Lysis and Prolonged Immune Responses in Melanoma.","authors":"Wu, Ye; Lu, Dong; Jiang, Yixin; Jin, Jinmei; Liu, Sanhong; Chen, Lili; Zhang, Hong; Zhou, Yudong; Chen, Hongzhuan; Nagle, Dale G; Luan, Xin; Zhang, Weidong","year":2021,"journal":"Journal of medicinal chemistry, 64(9), 5802-5815","doi":"10.1021/acs.jmedchem.0c02237","pmid":"33844923","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Stapled Ano-3/3s peptides showed superior tumor cell-selective cytotoxicity and induced tumor ablation in mice.","whyItMatters":"This research highlights a novel approach to enhance the effectiveness of oncolytic therapies, potentially leading to better cancer treatments. It also emphasizes the role of the immune system in combating tumors.","specificNumbers":"","methodology":"The study involved synthesizing stapled anoplin peptides and testing their effects on melanoma and triple-negative breast cancer in mouse models.","limitations":"The study was conducted in mouse models, and results may not directly translate to human patients."},{"rthcId":"RPEP-05882","title":"Inhibitory effect of LL-37 and human lactoferricin on growth and biofilm formation of anaerobes associated with oral diseases.","authors":"Wuersching, Sabina Noreen; Huth, Karin Christine; Hickel, Reinhard; Kollmuss, Maximilian","year":2021,"journal":"Anaerobe, 67, 102301","doi":"10.1016/j.anaerobe.2020.102301","pmid":"33249255","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"LL-37 inhibited growth and biofilm formation of oral bacteria with p < 0.0001; LfcinH had minimal effect.","whyItMatters":"Understanding how these peptides work could lead to new treatments for oral diseases. LL-37 shows potential as a therapeutic option, while Lactoferricin may not be suitable for this purpose.","specificNumbers":"","methodology":"The study involved incubating bacterial suspensions with varying concentrations of LL-37 and Lactoferricin, followed by measuring growth and biofilm formation using specific assays.","limitations":"The study did not fully elucidate the mechanisms of action for the AMPs, and Lactoferricin showed limited effectiveness."},{"rthcId":"RPEP-05883","title":"Targeting antibiotic tolerance in anaerobic biofilms associated with oral diseases: Human antimicrobial peptides LL-37 and lactoferricin enhance the antibiotic efficacy of amoxicillin, clindamycin and metronidazole.","authors":"Wuersching, Sabina Noreen; Huth, Karin Christine; Hickel, Reinhard; Kollmuss, Maximilian","year":2021,"journal":"Anaerobe, 71, 102439","doi":"10.1016/j.anaerobe.2021.102439","pmid":"34454095","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"LL-37 and lactoferricin enhanced the anti-biofilm effect of amoxicillin and clindamycin in facultative anaerobic biofilms (S. mutans, S. sanguinis, A. naeslundii). Metronidazole, which was ineffective alone against these biofilms, showed significant biofilm reduction when combined with either peptide.\n\nObligate anaerobic biofilms (V. parvula, P. micra, F. nucleatum) showed enhanced tolerance to amoxicillin and clindamycin, likely due to metabolic downshifts. However, combining these antibiotics with LL-37 or lactoferricin markedly enhanced biofilm reduction for all three antibiotics. The peptides also appeared to promote dispersion of mature biofilms, suggesting a mechanism for overcoming biofilm-mediated antibiotic tolerance.","whyItMatters":"Oral infections like periodontitis affect billions worldwide, and biofilm-forming bacteria are notoriously resistant to antibiotics. Rather than developing new antibiotics, this approach uses the body's own antimicrobial peptides to make existing antibiotics more effective. This 'combination therapy' strategy could address antibiotic tolerance without contributing to antibiotic resistance.","specificNumbers":"","methodology":"Researchers grew two types of polymicrobial biofilms in vitro: facultative anaerobic (representing caries-associated bacteria) and obligate anaerobic (representing periodontal disease-associated bacteria). They tested LL-37 and human lactoferricin alone and in combination with amoxicillin, clindamycin, and metronidazole, measuring biofilm reduction and bacterial viability.","limitations":"This is an in vitro study using laboratory-grown biofilms, which may not fully replicate the complexity of oral biofilms in the human mouth. The biofilm models used only 3 bacterial species each, while real oral biofilms contain hundreds of species. Peptide stability in saliva and the oral environment was not assessed. No in vivo or clinical data were generated. Cost and delivery challenges of antimicrobial peptides in clinical dental practice were not addressed."},{"rthcId":"RPEP-05884","title":"Identification of β-conglycinin α' subunit antigenic epitopes destroyed by thermal treatments.","authors":"Xi, Jun; Yao, LiLi; Li, Shuang","year":2021,"journal":"Food research international (Ottawa, Ont.), 139, 109806","doi":"10.1016/j.foodres.2020.109806","pmid":"33509449","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Heat treatments destroyed conformational epitopes but not linear epitopes in the α' subunit.","whyItMatters":"Understanding how heat affects allergenic proteins can help in developing safer food processing methods for individuals with soybean allergies.","specificNumbers":"","methodology":"The study employed phage display technology and enzyme-linked immunosorbent assay (iELISA) to identify and confirm the affected epitopes.","limitations":"The study primarily focused on in vitro methods, which may not fully replicate human responses."},{"rthcId":"RPEP-05885","title":"Structural and functional basis for pan-CoV fusion inhibitors against SARS-CoV-2 and its variants with preclinical evaluation.","authors":"Xia, Shuai; Wang, Lijue; Zhu, Yun; Lu, Lu; Jiang, Shibo","year":2021,"journal":"Signal transduction and targeted therapy, 6(1), 288","doi":"10.1038/s41392-021-00712-2","pmid":"34326308","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05886","title":"Targeting Triple Negative Breast Cancer with a Nucleus-Directed p53 Tetramerization Domain Peptide.","authors":"Xiao, Gu; Annor, George K; Fung, Kimberly; Keinänen, Outi; Zeglis, Brian M; Bargonetti, Jill","year":2021,"journal":"Molecular pharmaceutics, 18(1), 338-346","doi":"10.1021/acs.molpharmaceut.0c00978","pmid":"33289569","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Cy5p53Tet — a p53 tetramerization domain peptide conjugated to Cy5 fluorophore — showed higher nuclear uptake in TNBC MDA-MB-468 cells (with mutant p53 R273H) versus ER-positive MCF7 cells (with wild-type p53) by confocal microscopy and flow cytometry. Depletion of mutant p53 reduced peptide uptake, confirming target specificity. In mice bearing xenografts, Cy5p53Tet was detectable in tumor tissue within 12 minutes of injection. Significantly higher uptake was observed in mutant p53-expressing TNBC tumors compared to wild-type p53 tumors.","whyItMatters":"TNBC is the only major breast cancer subtype with no targeted therapy or detection method. Mutant p53 is present in over 80% of TNBCs, making it an ideal target. This peptide approach could serve dual purposes: helping surgeons see exactly where the cancer is during surgery (fluorescence-guided surgery) and potentially delivering toxic payloads directly to cancer cells. Finding and treating TNBC more precisely could improve outcomes for this aggressive cancer.","specificNumbers":"","methodology":"Researchers designed Cy5p53Tet containing the p53 tetramerization domain sequence conjugated to Cy5 fluorophore. Direct peptide-protein interaction was confirmed by co-immunoprecipitation and glutaraldehyde cross-linking. Cellular uptake was measured by confocal microscopy and flow cytometry in TNBC (MDA-MB-468, mutant p53) and ER-positive (MCF7, wild-type p53) cells. Target specificity was tested by p53 depletion experiments. In vivo imaging was performed in mice bearing MDA-MB-468 and MCF7 xenografts.","limitations":"Preclinical study in cell lines and mouse xenografts — human pharmacokinetics, biodistribution, and tumor-to-background ratios in clinical settings are unknown. The selectivity between mutant and wild-type p53 tumors was demonstrated but the absolute specificity in a patient (where both normal and cancerous tissues are present) needs validation. The 12-minute detection time is based on a mouse model — timing in humans may differ. No therapeutic efficacy was tested — only imaging. Peptide stability in human plasma was not assessed."},{"rthcId":"RPEP-05887","title":"Engineered Cell-Penetrating Peptides for Mitochondrion-Targeted Drug Delivery in Cancer Therapy.","authors":"Xiao, Qicai; Dong, Xiao; Yang, Fen; Zhou, Shizhe; Xiang, Menghua; Lou, Liang; Yao, Shao Q; Gao, Liqian","year":2021,"journal":"Chemistry (Weinheim an der Bergstrasse, Germany), 27(59), 14721-14729","doi":"10.1002/chem.202102523","pmid":"34436802","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"MTP3 showed high targeting ability with a strong correlation coefficient and effectively delivered a doxorubicin prodrug to tumor mitochondria.","whyItMatters":"This research highlights a novel method for delivering cancer therapies directly to mitochondria, potentially increasing treatment efficacy and reducing side effects.","specificNumbers":"","methodology":"The study involved synthesizing new mitochondrion-targeting peptides and testing their ability to deliver a doxorubicin prodrug to cancer cells.","limitations":"The study primarily focuses on in vitro results, which may not fully translate to in vivo effectiveness in humans."},{"rthcId":"RPEP-05888","title":"The immunomodulatory function of the porcine β-defensin 129: Alleviate inflammatory response induced by LPS in IPEC-J2 cells.","authors":"Xie, Kunhong; Su, Guoqi; Chen, Daiwen; Yu, Bing; Huang, Zhiqing; Yu, Jie; Zheng, Ping; Luo, Yuheng; Yan, Hui; Li, Hua; He, Jun","year":2021,"journal":"International journal of biological macromolecules, 188, 473-481","doi":"10.1016/j.ijbiomac.2021.07.194","pmid":"34352320","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"pBD129 reduced apoptosis in gut cells and down-regulated inflammatory cytokines IL-1β, IL-6, and TNFα (P < 0.05).","whyItMatters":"Understanding how pBD129 modulates inflammation could lead to new treatments for gut-related diseases in pigs and potentially other mammals.","specificNumbers":"","methodology":"The study involved expressing pBD129 in E. coli, followed by various assays to test its antibacterial and immunomodulatory effects on IPEC-J2 cells.","limitations":"The study primarily focuses on porcine cells, and results may not directly translate to human applications."},{"rthcId":"RPEP-05889","title":"Progress on the Function and Application of Thymosin β4.","authors":"Xing, Yuan; Ye, Yumeng; Zuo, Hongyan; Li, Yang","year":2021,"journal":"Frontiers in endocrinology, 12, 767785","doi":"10.3389/fendo.2021.767785","pmid":"34992578","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tβ4 is effective in treating conditions like myocardial infarction and ulcerative colitis.","whyItMatters":"Understanding Tβ4's role could lead to new treatments for serious health issues. Its multifunctional properties make it a valuable target for therapeutic interventions.","specificNumbers":"","methodology":"The study is a review of recent findings on Tβ4's functions and applications.","limitations":"The study primarily reviews existing literature and may not provide new experimental data."},{"rthcId":"RPEP-05890","title":"Human Defensins Inhibit SARS-CoV-2 Infection by Blocking Viral Entry.","authors":"Xu, Chuan; Wang, Annie; Marin, Mariana; Honnen, William; Ramasamy, Santhamani; Porter, Edith; Subbian, Selvakumar; Pinter, Abraham; Melikyan, Gregory B; Lu, Wuyuan; Chang, Theresa L","year":2021,"journal":"Viruses, 13(7)","doi":"10.3390/v13071246","pmid":"34206990","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"HNP1, HD5, and RC101 inhibited SARS-CoV-2 entry, while HNP4 and HD6 showed weak activity.","whyItMatters":"Understanding how human defensins work against SARS-CoV-2 could lead to new therapeutic strategies for COVID-19. This research highlights the potential of innate immune factors in combating viral infections.","specificNumbers":"","methodology":"The study tested the antiviral effects of various human defensins on pseudotyped and replication-competent SARS-CoV-2 viruses.","limitations":"The study primarily focused on in vitro models, which may not fully replicate human responses to infection."},{"rthcId":"RPEP-05891","title":"A Novel Peptide-Equipped Exosomes Platform for Delivery of Antisense Oligonucleotides.","authors":"Xu, Huiying; Liao, Chong; Liang, Shifu; Ye, Bang-Ce","year":2021,"journal":"ACS applied materials & interfaces, 13(9), 10760-10767","doi":"10.1021/acsami.1c00016","pmid":"33621039","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The modified exosomes increased cellular delivery of G3139 and downregulated Bcl-2.","whyItMatters":"This research offers a simpler method for delivering nucleic acids, which could enhance the effectiveness of cancer therapies. It also opens up new avenues for personalized medicine.","specificNumbers":"","methodology":"The study involved engineering exosomes with cell-penetrating peptides and testing their ability to deliver antisense oligonucleotides in vitro.","limitations":"The study was conducted in vitro, and results may not directly translate to human patients."},{"rthcId":"RPEP-05892","title":"MMP-7 derived peptides with MHC class-I binding motifs from canine mammary tumor tissue elicit strong antigen-specific T-cell responses in BALB/c mice.","authors":"Yadav, Pavan Kumar; Gupta, Shishir Kumar; Kumar, Saroj; Ghosh, Mayukh; Yadav, Brijesh Singh; Kumar, Dinesh; Kumar, Ajay; Saini, Mohini; Kataria, Meena","year":2021,"journal":"Molecular and cellular biochemistry, 476(1), 311-320","doi":"10.1007/s11010-020-03908-2","pmid":"32970284","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Two nonameric peptides (Peptide32-40 and Peptide175-183) identified from canine MMP-7 via immunoinformatics induced significant lymphocyte proliferation and IFN-γ production from CD8+ T cells in BALB/c mice immunized with a cMMP-7 DNA vaccine.\n\nThe DNA vaccine itself triggered strong CD8+ cytotoxic T lymphocyte (CTL) and Th1-type responses with high IFN-γ levels. The cross-species (xenovaccine) approach — using canine MMP-7 in mice — successfully overcame the immunological tolerance that typically limits vaccines targeting endogenous tumor-associated antigens.","whyItMatters":"MMP-7 is overexpressed in many human cancers and promotes tumor invasion and metastasis. Developing a vaccine that trains the immune system to attack MMP-7-expressing tumor cells could provide a new weapon against cancer spread. The xenovaccine strategy — using a slightly different species' version of the protein — is an innovative way to overcome the immune system's reluctance to attack its own proteins.","specificNumbers":"","methodology":"Immunoinformatics was used to predict MHC class-I binding peptides from canine MMP-7 protein sequence. A cMMP-7 DNA vaccine was constructed and administered to BALB/c mice. Immune responses were measured by assessing CD8+ T cell activation, lymphocyte proliferation, IFN-γ production, and antibody responses. The two predicted peptides were tested individually for their ability to stimulate T cells from vaccinated mice.","limitations":"This is a mouse study using a xenogeneic (cross-species) approach — results may not directly predict human immune responses. No tumor challenge experiments were described to confirm whether the immune response actually prevents or slows tumor growth. The MHC binding predictions were computational and the peptides were tested only in the context of prior DNA vaccination, not as standalone peptide vaccines."},{"rthcId":"RPEP-05893","title":"Structural insight into the dual function of LbpB in mediating Neisserial pathogenesis.","authors":"Yadav, Ravi; Govindan, Srinivas; Daczkowski, Courtney; Mesecar, Andrew; Chakravarthy, Srinivas; Noinaj, Nicholas","year":2021,"journal":"eLife, 10","doi":"10.7554/eLife.71683","pmid":"34751649","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"LbpB forms a 1:1 complex with lactoferrin, aiding in iron acquisition and immune evasion.","whyItMatters":"Understanding LbpB's dual role could lead to new strategies for combating Neisseria infections. This knowledge is crucial for developing therapies against these pathogens.","specificNumbers":"","methodology":"The study used structural analysis techniques, including size-exclusion chromatography and small-angle X-ray scattering, to examine the interactions between LbpB and lactoferrin.","limitations":"The study primarily focuses on structural insights and does not address in vivo effects or clinical implications."},{"rthcId":"RPEP-05894","title":"Hydrogel-Stiffening and Non-Cell Adhesive Properties of Amphiphilic Peptides with Central Alkylene Chains.","authors":"Yaguchi, Atsuya; Hiramatsu, Hirotsugu; Ishida, Atsuya; Oshikawa, Mio; Ajioka, Itsuki; Muraoka, Takahiro","year":2021,"journal":"Chemistry (Weinheim an der Bergstrasse, Germany), 27(36), 9295-9301","doi":"10.1002/chem.202100739","pmid":"33871881","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Peptides with a C2 alkylene chain formed the stiffest hydrogel, while longer chains reduced cell adhesion.","whyItMatters":"Understanding how to manipulate peptide properties can lead to better biomaterials for medical applications. This research could inform the design of materials that balance mechanical strength and biological functionality.","specificNumbers":"","methodology":"The study involved synthesizing amphiphilic peptides with varying lengths of central alkylene chains and assessing their self-assembly and biological properties.","limitations":"The study primarily focuses on the mechanical properties and cell adhesion, without exploring other biological interactions or in vivo applications."},{"rthcId":"RPEP-05895","title":"Angiotensin (1-7) Attenuates the Nociceptive Behavior Induced by Substance P and NMDA via Spinal MAS1.","authors":"Yamagata, Ryota; Nemoto, Wataru; Fujita, Maho; Nakagawasai, Osamu; Tan-No, Koichi","year":2021,"journal":"Biological & pharmaceutical bulletin, 44(5), 742-746","doi":"10.1248/bpb.b20-01004","pmid":"33952831","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Angiotensin (1-7) reduced nociceptive responses induced by SP and NMDA in a dose-dependent manner.","whyItMatters":"Understanding how angiotensin (1-7) works could lead to new pain management therapies. This research highlights a potential pathway for treating pain linked to specific receptors.","specificNumbers":"","methodology":"The study involved intrathecal injections of substance P and NMDA in animal models, followed by observation of pain behaviors and immunohistochemical analysis.","limitations":"The study was conducted in animal models, which may not fully translate to human pain responses."},{"rthcId":"RPEP-05896","title":"Exenatide Adjunct to Nicotine Patch Facilitates Smoking Cessation and May Reduce Post-Cessation Weight Gain: A Pilot Randomized Controlled Trial.","authors":"Yammine, Luba; Green, Charles E; Kosten, Thomas R; de Dios, Constanza; Suchting, Robert; Lane, Scott D; Verrico, Christopher D; Schmitz, Joy M","year":2021,"journal":"Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco, 23(10), 1682-1690","doi":"10.1093/ntr/ntab066","pmid":"33831213","tags":["glp-1-agonists","addiction-research"],"studyType":"randomized-controlled-trial","evidenceStrength":"moderate","keyFinding":"When added to the nicotine patch, exenatide (a GLP-1 receptor agonist) nearly doubled smoking quit rates: 46.3% of the exenatide group achieved abstinence versus 26.8% on placebo (risk ratio 1.70, posterior probability 96.5%). Exenatide also reduced cravings in the overall sample and withdrawal symptoms among those who quit.\n\nPost-cessation body weight was 5.6 pounds lower in the exenatide group compared to placebo (posterior probability 97.4%), addressing one of the most common barriers to quitting — weight gain. Adverse events were higher in the exenatide group (9.5% vs 2.3%) but the treatment was generally tolerable.","whyItMatters":"Smoking remains the leading cause of preventable death, and current quit medications have modest success rates. This trial is among the first to test a GLP-1 drug for smoking cessation in humans, building on animal studies showing GLP-1 receptor agonists reduce nicotine's rewarding effects. The dual benefit — higher quit rates plus less weight gain — makes this approach especially compelling since fear of gaining weight keeps many smokers from trying to quit.","specificNumbers":"n=84; 46.3% vs 26.8% abstinence; RR=1.70; 5.6 lbs less weight gain; 2 mg exenatide weekly; 21 mg nicotine patch; 6 weeks; PP=96.5% for abstinence; PP=97.4% for weight; AEs 9.5% vs 2.3%","methodology":"This was a pilot randomized controlled trial. Eighty-four prediabetic and/or overweight smokers were randomly assigned 1:1 to receive either once-weekly exenatide (2 mg subcutaneous injection) or placebo. All participants also received a 21 mg nicotine patch and brief smoking cessation counseling. Abstinence was verified by expired carbon monoxide levels (≤5 ppm) at 6 weeks. The study used Bayesian statistical analysis to quantify evidence for treatment effects.","limitations":"This was a small pilot study with only 84 participants and a short 6-week treatment period. The sample was limited to prediabetic and/or overweight smokers, so results may not generalize to all smokers. Longer follow-up is needed to determine whether quit rates persist. Adverse events were more common with exenatide. The study was not powered for definitive conclusions — larger confirmatory trials are needed."},{"rthcId":"RPEP-05897","title":"DT-diaphorase triggered theranostic nanoparticles induce the self-burst of reactive oxygen species for tumor diagnosis and treatment.","authors":"Yan, Dan; Xu, Xiao; Ren, Chunling; Chen, Chen; Luo, Jianguang; Han, Chao; Kong, Lingyi","year":2021,"journal":"Acta biomaterialia, 125, 267-279","doi":"10.1016/j.actbio.2021.02.033","pmid":"33652166","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The HTLAC nanosystem demonstrated dual theranostic (therapy + diagnostic) function:\n\n- In the presence of DT-diaphorase (overexpressed in tumors), the system simultaneously released withaferin A (anti-cancer) and activated the fluorescent probe DT-Cy5 (for tumor imaging)\n- Both enzyme-triggered reactions generated reactive oxygen species, and withaferin A itself produces additional intracellular ROS, creating a self-amplifying 'ROS burst'\n- Cell-penetrating peptide enhanced cellular uptake while hyaluronic acid provided active tumor targeting and prolonged blood circulation\n- In vitro and in vivo studies showed enhanced tumor detection, superior antitumor efficiency, and low systemic toxicity","whyItMatters":"Combining diagnosis and treatment in a single nanoparticle system — triggered specifically by a tumor enzyme — addresses two major challenges in cancer care: detecting tumors precisely and treating them with minimal collateral damage. The cell-penetrating peptide component is critical for enabling the nanoparticles to enter cancer cells efficiently, demonstrating the practical value of peptide technology in next-generation cancer nanomedicine.","specificNumbers":"","methodology":"The researchers synthesized DT-diaphorase-responsive prodrugs: DT-WA (withaferin A) and DT-Cy5 (fluorescent probe). These were encapsulated in liposomes functionalized with cell-penetrating peptide and hyaluronic acid. The nanoparticles were characterized for enzyme responsiveness, ROS generation, and fluorescence activation. Antitumor activity was assessed in vitro (cell proliferation, apoptosis, ROS measurements) and in vivo (tumor imaging, tumor growth inhibition, and systemic toxicity evaluation in animal models).","limitations":"The study used animal tumor models that may not fully replicate human cancer complexity. Specific quantitative outcomes (tumor volume reduction percentages, survival data, toxicity measurements) were not detailed in the abstract. Long-term safety and biodegradation of the nanoparticles were not assessed. The system's effectiveness depends on DT-diaphorase overexpression, which may vary across tumor types and individual patients."},{"rthcId":"RPEP-05898","title":"MOTS-c interacts synergistically with exercise intervention to regulate PGC-1α expression, attenuate insulin resistance and enhance glucose metabolism in mice via AMPK signaling pathway.","authors":"Yang, Boyu; Yu, Qiongli; Chang, Bo; Guo, Qi; Xu, Sitong; Yi, Xuejie; Cao, Shicheng","year":2021,"journal":"Biochimica et biophysica acta. Molecular basis of disease, 1867(6), 166126","doi":"10.1016/j.bbadis.2021.166126","pmid":"33722744","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05899","title":"Cost-effectiveness of GLP-1 receptor agonists versus insulin for the treatment of type 2 diabetes: a real-world study and systematic review.","authors":"Yang, Chen-Yi; Chen, Ying-Ren; Ou, Huang-Tz; Kuo, Shihchen","year":2021,"journal":"Cardiovascular diabetology, 20(1), 21","doi":"10.1186/s12933-020-01211-4","pmid":"33468131","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05900","title":"Comparative Effectiveness and Tolerability of the Pharmacology of Monoclonal Antibodies Targeting the Calcitonin Gene-Related Peptide and Its Receptor for the Prevention of Chronic Migraine: a Network Meta-analysis of Randomized Controlled Trials.","authors":"Yang, Chun-Pai; Zeng, Bing-Yan; Chang, Ching-Mao; Shih, Po-Hsuan; Yang, Cheng-Chia; Tseng, Ping-Tao; Wang, Shuu-Jiun","year":2021,"journal":"Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 18(4), 2639-2650","doi":"10.1007/s13311-021-01128-0","pmid":"34580838","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Eptinezumab reduced monthly migraine days by an average of 2.60 days compared to placebo.","whyItMatters":"These findings highlight the potential of CGRP monoclonal antibodies as effective alternatives to existing migraine treatments, which could improve patient outcomes.","specificNumbers":"","methodology":"The study conducted a network meta-analysis of randomized controlled trials comparing CGRP mAbs with traditional migraine treatments.","limitations":"The study's findings should be interpreted with caution due to several limitations, including variability in trial designs and patient populations."},{"rthcId":"RPEP-05901","title":"GLP-1 Receptor: A New Target for Sepsis.","authors":"Yang, Fuxun; Zeng, Fan; Luo, Xiaoxiu; Lei, Yu; Li, Jiajia; Lu, Sen; Huang, Xiaobo; Lan, Yunping; Liu, Rongan","year":2021,"journal":"Frontiers in pharmacology, 12, 706908","doi":"10.3389/fphar.2021.706908","pmid":"34335269","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies multiple potential benefits of GLP-1 receptor agonists in sepsis: regulation of blood glucose homeostasis (addressing stress hyperglycemia), improvement of organ dysfunction, modulation of immune responses, and control of inflammation. These properties suggest GLP-1RAs could serve as a new therapeutic approach for sepsis, particularly in patients with stress hyperglycemia — a common and dangerous complication.","whyItMatters":"Sepsis kills 11 million people annually worldwide and has limited targeted treatments beyond antibiotics and supportive care. Stress hyperglycemia during sepsis is a known mortality predictor, but insulin therapy for glucose control carries risks of hypoglycemia. GLP-1 agonists could be a safer glucose-lowering alternative that also provides independent organ-protective and anti-inflammatory benefits — potentially improving sepsis outcomes through multiple mechanisms.","specificNumbers":"","methodology":"Narrative review of published literature examining the potential applications of GLP-1 receptor agonists in sepsis, covering glucose regulation, organ protection, immune modulation, and anti-inflammatory effects.","limitations":"Brief narrative review without systematic search methodology. The abstract provides a high-level overview without specific preclinical or clinical data. No original experimental evidence is presented. The feasibility of administering GLP-1RAs to critically ill sepsis patients (who may have gastrointestinal dysfunction) is not addressed. Potential interactions with other sepsis treatments were not discussed. The evidence base at the time of publication was primarily preclinical."},{"rthcId":"RPEP-05902","title":"Self-Assembled Peptide Drug Delivery Systems.","authors":"Yang, Jia; An, Hong-Wei; Wang, Hao","year":2021,"journal":"ACS applied bio materials, 4(1), 24-46","doi":"10.1021/acsabm.0c00707","pmid":"35014275","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05903","title":"A self-assembled amphiphilic polysaccharide-based co-delivery system for egg white derived peptides and curcumin with oral bioavailability enhancement.","authors":"Yang, Meng; Liu, Jingbo; Li, Yajuan; Yang, Qi; Liu, Xuanting; Liu, Chunmei; Ma, Sitong; Liu, Boqun; Zhang, Ting; Xiao, Hang; Du, Zhiyang","year":2021,"journal":"Food & function, 12(21), 10512-10523","doi":"10.1039/d1fo01649k","pmid":"34568882","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The co-delivery system improved bioavailability of egg white peptides and curcumin compared to simple mixtures.","whyItMatters":"Improving the delivery of these nutraceuticals could enhance their health benefits, making them more effective for consumers. This research could lead to better formulations in food and health products.","specificNumbers":"","methodology":"The study used a self-assembled amphiphilic system to encapsulate curcumin and egg white peptides in nanoparticles.","limitations":"The study primarily focuses on in vitro results, which may not directly translate to human applications."},{"rthcId":"RPEP-05904","title":"Site-Specific Quantitation of Drug Conjugations on Antibody-Drug Conjugates (ADCs) Using a Protease-Assisted Drug Deconjugation and Linker-like Labeling (PADDLL) Method.","authors":"Yang, Xiangkun; Seol, Haeri; Lin, Wei; Xu, Xiaobin; Shen, Biao; Qiu, Haibo; Li, Ning","year":2021,"journal":"Analytical chemistry, 93(27), 9549-9558","doi":"10.1021/acs.analchem.1c01619","pmid":"34196532","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The PADDLL method achieved a limit of quantitation below 1% and demonstrated good linearity and reliability.","whyItMatters":"Accurate measurement of drug attachments on ADCs is crucial for their development and effectiveness in cancer treatment. This method could enhance the design and quality of future ADCs.","specificNumbers":"","methodology":"The study used a novel protease-assisted drug deconjugation and linker-like labeling method to quantify drug attachments on ADCs.","limitations":"The study primarily focuses on two specific ADCs, and further validation on a broader range of ADCs is needed."},{"rthcId":"RPEP-05905","title":"The use of impedance aggregometry to evaluate platelet function after the administration of DDAVP in healthy dogs treated with aspirin or clopidogrel.","authors":"Yankin, Igor; Carver, Andy M; Koenigshof, Amy M","year":2021,"journal":"American journal of veterinary research, 82(10), 823-828","doi":"10.2460/ajvr.82.10.823","pmid":"34554870","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"DDAVP did not significantly affect platelet aggregation in dogs treated with clopidogrel.","whyItMatters":"Understanding how DDAVP affects platelet function can help veterinarians make informed decisions about treating dogs with clotting disorders. This study indicates that DDAVP may not be beneficial for dogs on clopidogrel.","specificNumbers":"","methodology":"The study was a randomized double-blinded crossover design involving 7 healthy dogs, with platelet function assessed using impedance aggregometry before and after treatment with DDAVP.","limitations":"The small sample size of 7 dogs limits the generalizability of the findings."},{"rthcId":"RPEP-05906","title":"Response of Leucine-Rich Repeat Domain-Containing Protein in Haemaphysalis longicornis to Babesia microti Infection and Its Ligand Identification.","authors":"Yao, Jialing; Xu, Zhengmao; Sun, Zeyu; Zhou, Keke; Lu, Jinmiao; Mi, Rongsheng; Huang, Yan; Han, Xiangan; Ren, Keyi; Chen, Zhaoguo; Gong, Haiyan","year":2021,"journal":"Infection and immunity, 89(5)","doi":"10.1128/IAI.00268-20","pmid":"33593890","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Knockdown of HlLRR decreased BmActin mRNA expression and downregulated immune molecules in ticks.","whyItMatters":"Understanding how ticks respond to pathogens can lead to better strategies for controlling tick-borne diseases. This research may aid in the development of vaccines or drugs against Babesia.","specificNumbers":"","methodology":"The study utilized GST pulldown experiments and immunofluorescence assays, along with RNA interference techniques.","limitations":"The study primarily focuses on one tick species and one parasite, which may limit the generalizability of the findings."},{"rthcId":"RPEP-05907","title":"Electroacupuncture at Neurogenic Spots in Referred Pain Areas Attenuates Hepatic Damages in Bile Duct-Ligated Rats.","authors":"Yi, Yoo Jung; Kim, Do Hee; Chang, Suchan; Ryu, Yeonhee; Kim, Sang Chan; Kim, Hee Young","year":2021,"journal":"International journal of molecular sciences, 22(4)","doi":"10.3390/ijms22041974","pmid":"33671269","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Electroacupuncture reduced serum hepatocellular enzyme activities and improved liver injury patterns in bile duct ligation rats.","whyItMatters":"This research highlights a potential non-invasive treatment for liver injury, which could lead to new therapeutic approaches in veterinary and possibly human medicine.","specificNumbers":"","methodology":"The study involved a rat model of bile duct ligation to assess the effects of electroacupuncture at neurogenic spots.","limitations":"The study was conducted in rats, so results may not directly translate to humans."},{"rthcId":"RPEP-05908","title":"Tumor-Associated Neutrophil Extracellular Traps Regulating Nanocarrier-Enhanced Inhibition of Malignant Tumor Growth and Distant Metastasis.","authors":"Yin, Haoyuan; Lu, Hongdan; Xiong, Yaokun; Ye, Lu; Teng, Chuanhui; Cao, Xiang; Li, Shengnan; Sun, Shanbo; Liu, Wentao; Lv, Wei; Xin, Hongliang","year":2021,"journal":"ACS applied materials & interfaces, 13(50), 59683-59694","doi":"10.1021/acsami.1c18660","pmid":"34902970","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The mP-NPs-DNase/PTX nanocarrier significantly inhibited tumor growth and metastasis in both in vitro and in vivo models.","whyItMatters":"This research could lead to more effective cancer treatments by targeting the tumor microenvironment. By focusing on NETs, it opens new avenues for combating tumor growth and metastasis.","specificNumbers":"","methodology":"The study involved developing a smart nanocarrier and testing its effectiveness in degrading NETs and delivering paclitaxel to tumor cells through in vitro and in vivo evaluations.","limitations":"The study primarily focuses on preclinical models, so results may not directly translate to human patients."},{"rthcId":"RPEP-05909","title":"Cell-Penetrating Peptides: Emerging Tools for mRNA Delivery.","authors":"Yokoo, Hidetomo; Oba, Makoto; Uchida, Satoshi","year":2021,"journal":"Pharmaceutics, 14(1)","doi":"10.3390/pharmaceutics14010078","pmid":"35056974","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CPPs improve endosomal escape and mRNA delivery efficiency, particularly to dendritic cells.","whyItMatters":"Improving mRNA delivery systems could enhance the effectiveness of vaccines and treatments for various diseases. This research could lead to better therapeutic strategies using mRNA technology.","specificNumbers":"","methodology":"This is a review study that synthesizes existing research on CPPs and their applications in mRNA delivery.","limitations":"The review does not provide experimental data but rather summarizes existing literature, which may limit the depth of insights."},{"rthcId":"RPEP-05910","title":"Helical Antimicrobial Peptide Foldamers Containing Non-proteinogenic Amino Acids.","authors":"Yokoo, Hidetomo; Hirano, Motoharu; Misawa, Takashi; Demizu, Yosuke","year":2021,"journal":"ChemMedChem, 16(8), 1226-1233","doi":"10.1002/cmdc.202000940","pmid":"33565721","tags":[],"studyType":"review","evidenceStrength":"low","keyFinding":"This minireview surveys strategies for creating antimicrobial peptide (AMP) foldamers — synthetic peptide-like molecules that use non-natural amino acids to adopt stable helical structures. The approaches discussed include incorporating α,α-disubstituted amino acids, β-amino acids, γ-amino acids, side-chain stapling, and N-alkyl glycines. These modifications help AMPs maintain their membrane-disrupting amphipathic structure while potentially improving stability against enzymatic degradation and enhancing antimicrobial activity.","whyItMatters":"Natural antimicrobial peptides hold tremendous potential as alternatives to conventional antibiotics, but they are rapidly broken down by enzymes in the body. By incorporating non-proteinogenic (non-natural) amino acids, researchers can create foldamers that retain the membrane-disrupting properties of natural AMPs while resisting degradation. This approach could yield a new generation of antimicrobial drugs effective against resistant bacteria.","specificNumbers":"5 modification strategies reviewed: α,α-disubstituted amino acids · β-amino acids · γ-amino acids · side-chain stapling · N-alkyl glycines","methodology":"This is a minireview that summarizes and contextualizes recent published research on helical AMP foldamers. No original experimental data are presented.","limitations":"As a minireview, this paper provides a conceptual overview without original data. The abstract does not report specific antimicrobial efficacy, toxicity data, or in vivo results for any of the foldamers discussed. The practical challenges of translating foldamers into clinical drugs (cost, scalability, pharmacokinetics) are not addressed in the abstract."},{"rthcId":"RPEP-05911","title":"Effects of thymosin β4-derived peptides on migration and invasion of ovarian cancer cells.","authors":"Yoon, Hyung Joon; Oh, Young Lim; Ko, Eun-Ji; Kang, Ahyun; Eo, Wan Kyu; Kim, Ki Hyung; Lee, Ji Young; Kim, Ari; Chun, Sungwook; Kim, Hongbae; Ock, Mee Sun; Cha, Hee-Jae","year":2021,"journal":"Genes & genomics, 43(8), 987-993","doi":"10.1007/s13258-021-01127-7","pmid":"34170491","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tβ4 and its derived peptides significantly increased SKOV3 cell migration and invasion.","whyItMatters":"Understanding how Tβ4 peptides influence cancer cell behavior could lead to new therapeutic strategies for ovarian cancer. Targeting these pathways may help in managing metastasis in patients.","specificNumbers":"","methodology":"The study used in vitro assays to analyze the effects of Tβ4 and its peptides on SKOV3 ovarian cancer cells, including migration, invasion, and proliferation assays.","limitations":"The study is limited to in vitro experiments, and results may not directly translate to in vivo conditions or human patients."},{"rthcId":"RPEP-05912","title":"Antimicrobial Peptide LL-37 Drives Rosacea-Like Skin Inflammation in an NLRP3-Dependent Manner.","authors":"Yoon, Sung-Hyun; Hwang, Inhwa; Lee, Eunju; Cho, Hyo-Joung; Ryu, Ju Hee; Kim, Tae-Gyun; Yu, Je-Wook","year":2021,"journal":"The Journal of investigative dermatology, 141(12), 2885-2894.e5","doi":"10.1016/j.jid.2021.02.745","pmid":"33745908","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"LL-37 induced significant skin inflammation in mice, which was reduced in Nlrp3-deficient mice.","whyItMatters":"Understanding the role of LL-37 in rosacea can help develop targeted therapies for this common skin condition. It highlights the importance of the NLRP3 inflammasome in skin inflammation.","specificNumbers":"","methodology":"The study used in vitro experiments with macrophages and in vivo tests on mice to assess LL-37's effects on inflammation.","limitations":"The study primarily used animal models, which may not fully replicate human rosacea. Further research is needed to confirm these findings in humans."},{"rthcId":"RPEP-05913","title":"Recombinant human thymosin beta-4 (rhTβ4) improved scalp condition and microbiome homeostasis in seborrheic dermatitis.","authors":"Yu, Rui; Lin, Qingbin; Zhai, Yanfang; Mao, Yunyun; Li, Kai; Gao, Yuemei; Liu, Yanhong; Fu, Ling; Fang, Ting; Zhao, Mengsu; Guan, Lei; Hou, Lihua; Xu, Junjie; Chen, Wei","year":2021,"journal":"Microbial biotechnology, 14(5), 2152-2163","doi":"10.1111/1751-7915.13897","pmid":"34318587","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"rhTβ4 treatment was significantly more effective than ketoconazole in improving scalp conditions.","whyItMatters":"Finding effective treatments for seborrheic dermatitis is crucial since current options are limited. This research highlights a new potential therapy that not only alleviates symptoms but also restores scalp microbiome balance.","specificNumbers":"","methodology":"The study involved a 4-week treatment of 71 SD patients with rhTβ4 gel or ketoconazole lotion, comparing clinical and physiological outcomes.","limitations":"The study's sample size, while significant, may limit the generalizability of the findings, and long-term effects of rhTβ4 require further investigation."},{"rthcId":"RPEP-05914","title":"Recombinant Human Thymosin Beta-4 Protects against Mouse Coronavirus Infection.","authors":"Yu, Rui; Mao, Yunyun; Li, Kai; Zhai, Yanfang; Zhang, Yue; Liu, Shuling; Gao, Yuemei; Chen, Zhengshan; Liu, Yanhong; Fang, Ting; Zhao, Mengsu; Li, Ruihua; Xu, Junjie; Chen, Wei","year":2021,"journal":"Mediators of inflammation, 2021, 9979032","doi":"10.1155/2021/9979032","pmid":"33967626","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"rhTβ4 increased survival rate of infected mice and inhibited virus replication.","whyItMatters":"This research highlights a potential therapeutic approach for treating severe coronavirus infections in humans, such as COVID-19. Understanding how Tβ4 functions could lead to new treatments.","specificNumbers":"","methodology":"The study used a BALB/c mouse model infected with mouse hepatitis virus (MHV-A59) to evaluate the effects of recombinant human Tβ4.","limitations":"The study was conducted in mice, and results may not directly translate to humans. Further research is needed to confirm efficacy in human subjects."},{"rthcId":"RPEP-05915","title":"Efficient intracellular delivery of proteins by a multifunctional chimaeric peptide in vitro and in vivo.","authors":"Yu, Siyuan; Yang, Han; Li, Tingdong; Pan, Haifeng; Ren, Shuling; Luo, Guoxing; Jiang, Jinlu; Yu, Linqi; Chen, Binbing; Zhang, Yali; Wang, Shaojuan; Tian, Rui; Zhang, Tianying; Zhang, Shiyin; Chen, Yixin; Yuan, Quan; Ge, Shengxiang; Zhang, Jun; Xia, Ningshao","year":2021,"journal":"Nature communications, 12(1), 5131","doi":"10.1038/s41467-021-25448-z","pmid":"34446736","tags":["cell-penetrating-peptides","drug-delivery","protein-therapeutics"],"studyType":"preclinical","evidenceStrength":"preclinical-animal","keyFinding":"Researchers engineered a four-module chimeric peptide system that solves two major problems with cell-penetrating peptide drug delivery: poor endosomal escape (cargo gets trapped inside cellular compartments) and degradation in blood serum.\n\nThe system chains together: (1) a cell-penetrating peptide to enter cells, (2) a pH-sensitive membrane-active peptide that activates in acidic endosomes, (3) protease cleavage sites that release cargo when cut by endosome-specific enzymes, and (4) a leucine zipper that dimerizes the construct for enhanced function. When used to deliver the therapeutic protein phosphatase 1B (PTP1B) intravenously in mice, it successfully suppressed TNF-α-induced systemic inflammation and prevented acetaminophen-induced acute liver failure.","whyItMatters":"Many promising drug targets sit inside cells, but getting large protein drugs through cell membranes and out of endosomal traps has been a major barrier. This modular peptide system demonstrates that combining multiple functional peptide elements can overcome both challenges simultaneously, opening the door to a new class of protein-based drugs that work against intracellular targets.","specificNumbers":"4-module chimeric peptide system · Enhanced endosomal escape via pH-triggered + protease-triggered dual mechanism · Suppressed TNF-α inflammation in mice · Prevented acetaminophen-induced liver failure in mice","methodology":"The researchers designed and synthesized a four-module chimeric peptide, tested protein delivery efficiency in cell culture (in vitro), and validated therapeutic efficacy in two mouse models: TNF-α-induced systemic inflammatory response and acetaminophen-induced acute liver failure. The therapeutic protein PTP1B was fused to the chimeric peptide and delivered via intravenous injection.","limitations":"This is a mouse study — efficacy and safety in humans are unknown. The specific therapeutic protein used (PTP1B) may behave differently than other cargo proteins. Manufacturing complexity of a four-module chimeric construct could pose challenges for clinical development. Long-term effects and immunogenicity were not assessed."},{"rthcId":"RPEP-05916","title":"Antibody-siRNA conjugates (ARCs) using multifunctional peptide as a tumor enzyme cleavable linker mediated effective intracellular delivery of siRNA.","authors":"Yu, Zhili; Zhang, Xiaojuan; Pei, Xing; Cao, Weiran; Ye, Junxiao; Wang, Jianxin; Sun, Lu; Yu, Fei; Wang, Jiancheng; Li, Nan; Lee, Kyuri; Barth, Stefan; Yang, Victor C; He, Huining","year":2021,"journal":"International journal of pharmaceutics, 606, 120940","doi":"10.1016/j.ijpharm.2021.120940","pmid":"34310959","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Achieved 66.7% downregulation of EGFP in tumor-bearing mice.","whyItMatters":"This research addresses significant challenges in siRNA delivery for cancer treatment, potentially improving therapeutic outcomes. The method could enhance the specificity and efficiency of gene silencing in tumors.","specificNumbers":"","methodology":"The study utilized a multifunctional peptide linker for antibody-siRNA conjugation and tested the system in vitro and in vivo.","limitations":"The study primarily focused on a specific tumor model, which may limit the generalizability of the findings to other types of cancers."},{"rthcId":"RPEP-05917","title":"Research progress of ghrelin on cardiovascular disease.","authors":"Yuan, Ming-Jie; Li, Wei; Zhong, Peng","year":2021,"journal":"Bioscience reports, 41(1)","doi":"10.1042/BSR20203387","pmid":"33427286","tags":[],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Ghrelin, a 28-amino-acid peptide from the stomach, has multiple cardioprotective effects beyond its well-known role in appetite and growth hormone. Research shows ghrelin modulates sympathetic nervous system activity and blood pressure, enhances blood vessel function and new vessel growth (angiogenesis), inhibits cardiac arrhythmias, reduces heart failure progression, and inhibits harmful cardiac remodeling after heart attacks.\n\nThe underlying mechanisms include anti-inflammatory effects, prevention of cell death (anti-apoptosis), suppression of sympathetic nerve overactivation, regulation of autophagy, and correction of endothelial dysfunction. However, the molecular details remain incompletely understood and no ghrelin-based cardiovascular drug exists yet.","whyItMatters":"Heart disease remains the leading cause of death globally, and the discovery that a stomach peptide protects the heart opens unexpected therapeutic avenues. Ghrelin's broad cardioprotective profile — spanning blood pressure, arrhythmias, heart failure, and post-heart-attack remodeling — suggests it targets fundamental cardiovascular processes. Developing ghrelin pathway drugs could provide new treatments for conditions where current options are limited.","specificNumbers":"28-amino-acid peptide · Identified 1999 · Receptor: GHS-R1a · Cardioprotective effects: anti-hypertensive, anti-arrhythmic, anti-remodeling, pro-angiogenic · Mechanisms: anti-inflammatory, anti-apoptotic, sympatholytic","methodology":"Narrative review of published research on ghrelin's cardiovascular effects, covering studies on hypertension, vascular function, arrhythmias, heart failure, and post-myocardial infarction remodeling. Discusses proposed molecular mechanisms including inflammatory, apoptotic, autophagy, and endothelial pathways.","limitations":"Narrative review — not a systematic review or meta-analysis. Most cardiovascular ghrelin research is preclinical (cell and animal studies); human clinical data is limited. No ghrelin-based cardiovascular therapy has reached clinical trials. The multiple proposed mechanisms suggest the field is still early and the exact therapeutic targets remain unclear."},{"rthcId":"RPEP-05918","title":"Cytotoxicity and Immunogenicity Evaluation of Synthetic Cell-penetrating Peptides for Methotrexate Delivery.","authors":"Zakeri-Milani, Parvin; Najafi-Hajivar, Saeedeh; Sarfraz, Muhammad; Nokhodchi, Ali; Mohammadi, Hamed; Montazersaheb, Soheila; Niazi, Mehri; Hemmatzadeh, Maryam; Soleymani-Goloujeh, Mehdi; Baradaran, Behzad; Shahbazi Mojarrad, Javid; Farshbaf, Masoud; Gholikhani, Tooba; Valizadeh, Hadi","year":2021,"journal":"Iranian journal of pharmaceutical research : IJPR, 20(3), 506-515","doi":"10.22037/ijpr.2021.114429.14842","pmid":"34904004","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"W4R4-MTX showed a loading efficiency of 97% and a drug to peptide percentage of 24.02%.","whyItMatters":"Improving the delivery of methotrexate can enhance its effectiveness against tumors while minimizing side effects. This research could lead to better cancer treatment options.","specificNumbers":"","methodology":"The study involved synthesizing CPPs, preparing peptide-MTX conjugates, and evaluating their cytotoxicity and immunogenicity using various assays.","limitations":"The study primarily focuses on in vitro results, and further research is needed to confirm effectiveness in vivo."},{"rthcId":"RPEP-05919","title":"Development and Regulatory Challenges for Peptide Therapeutics.","authors":"Zane, Doris; Feldman, Paul L; Sawyer, Tomi; Sobol, Zhanna; Hawes, Jessica","year":2021,"journal":"International journal of toxicology, 40(2), 108-124","doi":"10.1177/1091581820977846","pmid":"33327828","tags":[],"studyType":"review","evidenceStrength":"review","keyFinding":"Peptide therapeutics entering clinical development have increased significantly over the past decade, but regulatory frameworks haven't kept pace. A key challenge: existing FDA/ICH guidelines (ICH M3(R2) for small molecules and ICH S6(R1) for biologics) were not designed for peptides, which fall somewhere in between. Regulators and drug companies interpret these guidelines differently for synthetic and conjugated peptides, creating inconsistency in nonclinical testing requirements.\n\nThe symposium addressed four specific challenges: (1) discovery and optimization of combination peptide therapeutics, (2) toxicological requirements for peptide drug-device combination products (like auto-injectors), (3) regulatory classification disputes — are synthetic peptides drugs or biologics? — and (4) genotoxicity testing requirements, which may be unnecessary for many peptides but are still often required.","whyItMatters":"The peptide drug market is booming (GLP-1 agonists alone are projected to exceed $100 billion), but the regulatory path for bringing new peptides to market remains unclear. When regulators and companies disagree on whether a peptide should be regulated as a small molecule or a biologic, it can add years and millions to development timelines. Clarifying these rules would accelerate the pipeline of peptide therapeutics for diseases with unmet needs.","specificNumbers":"40th Annual Meeting of American College of Toxicology (2019) · ICH M3(R2) and ICH S6(R1) guidelines discussed · 2016 HESI Genetic Toxicology Technical Committee assessment reviewed · Significant increase in peptide drugs in clinical development over the past decade","methodology":"Summary of a symposium at the 40th Annual Meeting of the American College of Toxicology (November 2019), featuring industry and regulatory scientists presenting and discussing regulatory challenges for peptide therapeutics.","limitations":"This is a symposium summary, not original research. It presents perspectives from a specific meeting rather than a systematic analysis of the regulatory landscape. Published in 2021, it predates the GLP-1 agonist market explosion and the FDA's 2023 peptide-specific guidance updates. Focuses primarily on US FDA regulation with limited international perspective."},{"rthcId":"RPEP-05920","title":"The Influence of Specific Bioactive Collagen Peptides on Body Composition and Muscle Strength in Middle-Aged, Untrained Men: A Randomized Controlled Trial.","authors":"Zdzieblik, Denise; Jendricke, Patrick; Oesser, Steffen; Gollhofer, Albert; König, Daniel","year":2021,"journal":"International journal of environmental research and public health, 18(9)","doi":"10.3390/ijerph18094837","pmid":"33946565","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Collagen peptide group saw a 2.4 kg increase in fat-free mass and a 1.2 kg decrease in fat mass compared to placebo.","whyItMatters":"This research highlights the potential of collagen peptides as a supplement for improving body composition and muscle strength, particularly in middle-aged men who are untrained.","specificNumbers":"","methodology":"A randomized controlled trial with 97 participants divided into three groups receiving different supplements during a 12-week resistance training program.","limitations":"The study focused only on middle-aged, untrained men, limiting generalizability to other demographics."},{"rthcId":"RPEP-05921","title":"The Influence of Specific Bioactive Collagen Peptides on Knee Joint Discomfort in Young Physically Active Adults: A Randomized Controlled Trial.","authors":"Zdzieblik, Denise; Brame, Judith; Oesser, Steffen; Gollhofer, Albert; König, Daniel","year":2021,"journal":"Nutrients, 13(2)","doi":"10.3390/nu13020523","pmid":"33562729","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Participants taking collagen peptides experienced a 21.9 mm reduction on the Visual Analog Scale (VAS) for exercise-induced knee pain, compared to 15.6 mm for placebo (p = 0.024). Physician evaluations showed an even clearer difference: 23.0 mm reduction versus 14.6 mm (p = 0.003).\n\nPain at rest and after performing 20 squats did not differ significantly between groups, but this was largely because few participants had pain under those conditions at baseline. Joint mobility was clinically unremarkable at the start and remained unchanged.","whyItMatters":"Exercise-related joint discomfort is extremely common in active young adults, yet most joint health research focuses on older populations with arthritis. This confirmatory trial shows that a simple, affordable collagen peptide supplement can meaningfully reduce activity-related knee pain in otherwise healthy young people — a population that typically has few options beyond rest and anti-inflammatory drugs.","specificNumbers":"","methodology":"This was a randomized, double-blind, placebo-controlled trial. 180 physically active men and women aged 18–30 with exercise-related knee pain but no diagnosed joint disease were randomly assigned to receive either 5 grams of specific type I collagen peptides (mean molecular weight 3 kDa) or placebo daily for 12 weeks. Pain was measured using the Visual Analog Scale (VAS) both by participants and examining physicians. Secondary outcomes included pain at rest, pain after squats, knee mobility, and use of alternative therapies.","limitations":"The pain reduction, while statistically significant, was modest in absolute terms (about 6 mm difference on a 100 mm VAS scale). The study was funded by a collagen peptide manufacturer (GELITA AG), and one author is a company employee. The 12-week duration doesn't reveal whether benefits persist long-term. Only activity-related pain was significantly affected — resting pain and joint mobility showed no benefit."},{"rthcId":"RPEP-05922","title":"Chemerin-Derived Peptide Val66-Pro85 Is Effective in Limiting Methicillin-Resistant S. aureus Skin Infection.","authors":"Zegar, Aneta; Godlewska, Urszula; Kozłowska-Chmielewska, Dorota; Majewski, Pawel; Zabel, Brian A; Cichy, Joanna","year":2021,"journal":"Frontiers in microbiology, 12, 742610","doi":"10.3389/fmicb.2021.742610","pmid":"34803962","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Val66-Pro85 effectively reduced MRSA burden and skin-infiltrating leukocytes in infected models.","whyItMatters":"This research highlights a potential new treatment for MRSA skin infections, which are difficult to manage due to antibiotic resistance. The findings could lead to better management of skin inflammatory diseases linked to S. aureus.","specificNumbers":"","methodology":"The study compared the activity of Val66-Pro85 against MRSA in vitro and in vivo, using models of skin infection and inflammation.","limitations":"The study primarily focuses on in vitro and animal models, which may not fully translate to human outcomes."},{"rthcId":"RPEP-05923","title":"Pentadecapeptide BPC 157 counteracts L-NAME-induced catalepsy. BPC 157, L-NAME, L-arginine, NO-relation, in the suited rat acute and chronic models resembling 'positive-like' symptoms of schizophrenia.","authors":"Zemba Cilic, Andrea; Zemba, Mladen; Cilic, Matija; Balenovic, Igor; Strbe, Sanja; Ilic, Spomenko; Vukojevic, Jaksa; Zoricic, Zoran; Filipcic, Igor; Kokot, Antonio; Drmic, Domagoj; Blagaic, Alenka Boban; Tvrdeic, Ante; Seiwerth, Sven; Sikiric, Predrag","year":2021,"journal":"Behavioural brain research, 396, 112919","doi":"10.1016/j.bbr.2020.112919","pmid":"32956773","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BPC 157 counteracted catalepsy and other symptoms induced by L-NAME and methamphetamine in rats.","whyItMatters":"These findings suggest that BPC 157 may have therapeutic potential for treating schizophrenia-like symptoms, which could lead to new treatment options.","specificNumbers":"","methodology":"The study used suited rat models and administered various doses of BPC 157, L-NAME, and L-arginine to evaluate their effects on induced symptoms.","limitations":"The study was conducted in rat models, and results may not directly translate to humans. Further research is needed to clarify the mechanisms involved."},{"rthcId":"RPEP-05924","title":"A pro-diabetogenic mtDNA polymorphism in the mitochondrial-derived peptide, MOTS-c.","authors":"Zempo, Hirofumi; Kim, Su-Jeong; Fuku, Noriyuki; Nishida, Yuichiro; Higaki, Yasuki; Wan, Junxiang; Yen, Kelvin; Miller, Brendan; Vicinanza, Roberto; Miyamoto-Mikami, Eri; Kumagai, Hiroshi; Naito, Hisashi; Xiao, Jialin; Mehta, Hemal H; Lee, Changhan; Hara, Megumi; Patel, Yesha M; Setiawan, Veronica W; Moore, Timothy M; Hevener, Andrea L; Sutoh, Yoichi; Shimizu, Atsushi; Kojima, Kaname; Kinoshita, Kengo; Arai, Yasumichi; Hirose, Nobuyoshi; Maeda, Seiji; Tanaka, Keitaro; Cohen, Pinchas","year":2021,"journal":"Aging, 13(2), 1692-1717","doi":"10.18632/aging.202529","pmid":"33468709","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Men with the C-allele of m.1382A>C showed a higher prevalence of T2D, particularly in low physical activity groups.","whyItMatters":"Understanding the genetic factors that contribute to T2D can help in developing targeted prevention strategies, especially in high-risk populations. This research highlights the importance of considering genetic variations in the context of lifestyle factors like physical activity.","specificNumbers":"","methodology":"The study involved a meta-analysis of three cohorts totaling 27,527 participants, alongside animal experiments using high-fat fed male mice.","limitations":"The study primarily focuses on male participants, limiting the applicability of findings to females. Additionally, results from animal models may not fully translate to human conditions."},{"rthcId":"RPEP-05925","title":"Computational design and experimental substantiation of conformationally constrained peptides from the complex interfaces of transcriptional enhanced associate domains with their cofactors in gastric cancer.","authors":"Zhang, Donglei; Wu, Hongna; Zhao, Jing","year":2021,"journal":"Computational biology and chemistry, 94, 107569","doi":"10.1016/j.compbiolchem.2021.107569","pmid":"34500324","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Cyclized and stapled peptides showed improved affinity for Tead cofactors, maintaining selectivity.","whyItMatters":"These findings could lead to the development of new therapeutic strategies for gastric cancer by targeting specific protein interactions.","specificNumbers":"","methodology":"The study involved computational design and experimental validation of peptide modifications to enhance binding to Tead-cofactor complexes.","limitations":"The study primarily focuses on in vitro findings, which may not fully translate to in vivo conditions."},{"rthcId":"RPEP-05926","title":"Macrocyclic Peptides that Selectively Inhibit the Mycobacterium tuberculosis Proteasome.","authors":"Zhang, Hao; Hsu, Hao-Chi; Kahne, Shoshanna C; Hara, Ryoma; Zhan, Wenhu; Jiang, Xiuju; Burns-Huang, Kristin; Ouellette, Tierra; Imaeda, Toshihiro; Okamoto, Rei; Kawasaki, Masanori; Michino, Mayako; Wong, Tzu-Tshin; Toita, Akinori; Yukawa, Takafumi; Moraca, Francesca; Vendome, Jeremie; Saha, Priya; Sato, Kenjiro; Aso, Kazuyoshi; Ginn, John; Meinke, Peter T; Foley, Michael; Nathan, Carl F; Darwin, K Heran; Li, Huilin; Lin, Gang","year":2021,"journal":"Journal of medicinal chemistry, 64(9), 6262-6272","doi":"10.1021/acs.jmedchem.1c00296","pmid":"33949190","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Macrocycle 6 selectively inhibits Mtb20S, leading to the death of nonreplicating Mtb.","whyItMatters":"Targeting the Mtb proteasome could significantly improve tuberculosis treatment by effectively addressing drug-resistant forms of the bacteria. This research opens new avenues for developing faster-acting anti-TB therapies.","specificNumbers":"","methodology":"The study involved synthesizing macrocyclic peptides and assessing their effects on Mtb proteasome inhibition and bacterial viability.","limitations":"The study primarily focuses on in vitro results, and further research is needed to confirm efficacy in vivo and in clinical settings."},{"rthcId":"RPEP-05927","title":"Association between Thymosin beta-4, acute kidney injury, and mortality in patients with sepsis: An observational cohort study.","authors":"Zhang, Jiahao; Long, Minghui; Sun, Zhongyi; Yang, Cheng; Jiang, Xiaofang; He, Li; Su, Lianjiu; Peng, Zhiyong","year":2021,"journal":"International immunopharmacology, 101(Pt A), 108167","doi":"10.1016/j.intimp.2021.108167","pmid":"34607232","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 191 sepsis patients divided into Tβ4 concentration tertiles (1.19–7.11, 7.12–11.01, and 11.02–28.10 ng/ml), lower Tβ4 was significantly associated with worse outcomes:\n\n- Acute kidney injury: OR 2.102 per stage lower (95% CI 1.448–3.050, p<0.001)\n- Need for continuous renal replacement therapy: OR 2.346 per stage lower (95% CI 1.287–4.276, p=0.005)\n- 7-day mortality: OR 1.755 per stage lower (95% CI 1.050–2.935, p=0.032)\n- 28-day mortality: OR 1.821 per stage lower (95% CI 1.209–2.743, p=0.004)\n\nThe predictive accuracy (AUC) for each outcome ranged from 0.682 to 0.717. Kaplan-Meier analysis confirmed that patients in lower Tβ4 tertiles had significantly higher cumulative risks of AKI and death.","whyItMatters":"Sepsis kills millions of people annually, and early identification of the highest-risk patients is critical for guiding aggressive treatment. Current biomarkers like procalcitonin and lactate have limitations. Thymosin beta-4 offers a new prognostic tool that reflects the body's anti-inflammatory peptide reserves — lower levels may indicate exhausted protective mechanisms. If validated, Tβ4 testing could help ICU teams make faster decisions about dialysis initiation and treatment escalation.","specificNumbers":"","methodology":"This was a prospective observational cohort study of 191 patients admitted to the ICU with sepsis. Tβ4 concentrations were measured in blood samples taken within 6 hours of ICU admission. Patients were divided into tertiles based on Tβ4 levels. Outcomes included acute kidney injury, need for continuous renal replacement therapy, and mortality at 7 and 28 days. Logistic regression was used to calculate odds ratios, and Kaplan-Meier survival analysis assessed time-to-event outcomes. AUC (area under the curve) was calculated for predictive accuracy.","limitations":"This is an observational study and cannot prove that low Tβ4 causes worse outcomes — it may simply reflect disease severity. The AUC values (0.68–0.72) indicate moderate, not excellent, predictive accuracy. The study was conducted at a single center with 191 patients, which may limit generalizability. Confounding factors may not be fully controlled. Whether Tβ4 supplementation could improve outcomes was not tested."},{"rthcId":"RPEP-05928","title":"A Novel Mechanism of Carvedilol Efficacy for Rosacea Treatment: Toll-Like Receptor 2 Inhibition in Macrophages.","authors":"Zhang, Jiawen; Jiang, Peiyu; Sheng, Lei; Liu, Yunyi; Liu, Yixuan; Li, Min; Tao, Meng; Hu, Liang; Wang, Xiaoyan; Yang, Yanjing; Xu, Yang; Liu, Wentao","year":2021,"journal":"Frontiers in immunology, 12, 609615","doi":"10.3389/fimmu.2021.609615","pmid":"34322115","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Carvedilol reduced TLR2 expression and improved skin redness in rosacea patients over 6 months.","whyItMatters":"Understanding carvedilol's mechanism provides new insights into treating rosacea, potentially leading to better management of this chronic condition.","specificNumbers":"","methodology":"The study involved histopathological and immunohistochemical evaluations of skin samples from rosacea patients, an in vivo mouse model of rosacea, and in vitro tests on immune cells.","limitations":"The study primarily used mouse models, which may not fully replicate human responses, and the sample size for human evaluations was not detailed."},{"rthcId":"RPEP-05929","title":"Peptide Szeto‑Schiller 31 ameliorates doxorubicin‑induced cardiotoxicity by inhibiting the activation of the p38 MAPK signaling pathway.","authors":"Zhang, Li; Feng, Mengwen; Wang, Xuejun; Zhang, Hao; Ding, Jingjing; Cheng, Zijie; Qian, Lingmei","year":2021,"journal":"International journal of molecular medicine, 47(4)","doi":"10.3892/ijmm.2021.4896","pmid":"33649779","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"SS31 reduced reactive oxygen species and improved heart cell survival in DOX-treated models.","whyItMatters":"Doxorubicin is a common cancer treatment that can cause serious heart damage. Finding ways to protect the heart during treatment is crucial for improving patient outcomes.","specificNumbers":"","methodology":"The study used H9c2 heart cells and C57BL/6 mice to model doxorubicin-induced cardiotoxicity and assessed the effects of SS31.","limitations":"The study was conducted in vitro and in mice, so results may not directly translate to humans."},{"rthcId":"RPEP-05930","title":"Diet-induced obesity promotes infection by impairment of the innate antimicrobial defense function of dermal adipocyte progenitors.","authors":"Zhang, Ling-Juan; Guerrero-Juarez, Christian F; Chen, Stella X; Zhang, Xiaowei; Yin, Meimei; Li, Fengwu; Wu, Shuai; Chen, Joyce; Li, Min; Liu, Yingzi; Jiang, Shang I B; Hata, Tissa; Plikus, Maksim V; Gallo, Richard L","year":2021,"journal":"Science translational medicine, 13(577)","doi":"10.1126/scitranslmed.abb5280","pmid":"33472955","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Diet-induced obesity led to a loss of adipocyte progenitors and increased susceptibility to Staphylococcus aureus infection.","whyItMatters":"Understanding how obesity impairs skin defenses can help develop new treatments for infections in obese patients. This research highlights a critical link between obesity and increased infection risk.","specificNumbers":"","methodology":"The study involved both human and mouse models to investigate the effects of diet-induced obesity on skin cells and infection susceptibility.","limitations":"The study primarily used mouse models, which may not fully replicate human responses to obesity and infection."},{"rthcId":"RPEP-05931","title":"Novel XTENylated AWRK6 analog with hypoglycemic activity, and anti-HSV-2 potential in combination with double shRNA.","authors":"Zhang, Xiaomin; Gao, Shuying; Liu, Maosheng; Wei, Nina; Zhang, Qingfeng; Li, Xiangyang; Niu, Xianli","year":2021,"journal":"Life sciences, 274, 119313","doi":"10.1016/j.lfs.2021.119313","pmid":"33667511","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"XA-4 demonstrated significant hypoglycemic effects and antiviral activity against HSV-2.","whyItMatters":"This research highlights a potential dual-action treatment for diabetes and viral infections, which could improve patient outcomes significantly. The innovative approach of XTENylation may enhance the effectiveness of other therapeutic peptides.","specificNumbers":"","methodology":"The study involved synthesizing four peptide analogs, assessing their binding and activation through various assays, and conducting in vivo tests in rodent models.","limitations":"The study was conducted in rodent models, which may not fully translate to human outcomes."},{"rthcId":"RPEP-05932","title":"Virus-Mimicking Mesoporous Silica Nanoparticles with an Electrically Neutral and Hydrophilic Surface to Improve the Oral Absorption of Insulin by Breaking Through Dual Barriers of the Mucus Layer and the Intestinal Epithelium.","authors":"Zhang, Yi; Xiong, Mengting; Ni, Xiaomin; Wang, Jingrou; Rong, Hehui; Su, Yuqing; Yu, Shihui; Mohammad, Imran Shair; Leung, Sharon Shui Yee; Hu, Haiyan","year":2021,"journal":"ACS applied materials & interfaces, 13(15), 18077-18088","doi":"10.1021/acsami.1c00580","pmid":"33830730","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Virus-mimicking mesoporous silica nanoparticles coated with the cell-penetrating peptide KLPVM and glutaric anhydride achieved near-neutral surface charge (ζ-potential -0.49 mV), enabling them to penetrate the intestinal mucus layer without binding to mucin — unlike positively charged nanoparticles (ζ-potential +35.00 mV). Transepithelial transport was 2.4-fold higher than unmodified nanoparticles. In diabetic rats, insulin loaded into these nanoparticles reduced blood glucose by nearly 50%, with 2.1-fold higher bioavailability than insulin administered directly into the jejunum. No significant toxicity was observed in preliminary in vitro or in vivo studies.","whyItMatters":"Insulin and most peptide drugs cannot currently be taken orally because they are destroyed in the stomach and cannot pass through the intestinal mucus and epithelial barriers. This virus-mimicking approach solves both problems simultaneously — using a neutral, hydrophilic surface to slip through mucus (like viruses do) and a cell-penetrating peptide to cross the intestinal wall. Success here could transform diabetes management and open the door for oral delivery of many other peptide therapeutics.","specificNumbers":"6 nm pore diameter · ζ-potential: -0.49 mV (neutral) · Permeability: 14.61 × 10⁻⁵ cm/s · 2.4-fold higher transport vs. unmodified · ~50% blood glucose reduction · 2.1-fold bioavailability increase · No significant toxicity","methodology":"Researchers fabricated mesoporous silica nanoparticles with 6 nm pores for insulin loading, then coated them with the cationic cell-penetrating peptide KLPVM and anionic glutaric anhydride to create a near-neutral surface. Mucus penetration was tested against mucin in vitro. Intestinal transport was measured using Caco-2/E12 cell co-culture models. Endocytosis pathways were characterized. Insulin stability was confirmed under simulated intestinal conditions. In vivo testing in diabetic rats measured blood glucose reduction and insulin bioavailability compared to direct jejunal insulin administration.","limitations":"While the diabetic rat results are promising, animal models do not always predict human responses. The study used relatively small numbers of animals and did not assess long-term safety or repeated dosing. The manufacturing scalability of these nanoparticles for commercial production was not addressed. Human clinical trials would be needed to confirm efficacy and safety."},{"rthcId":"RPEP-05933","title":"Anti-Psoriatic Effects of Middle Fragment of Chlamydial Plasmid-Encoded Protein pGP3 in an Imiquimod-Induced Psoriasis Mouse Model.","authors":"Zhang, Yiming; Ma, Miaomiao; Li, Jun; Wu, Yingye; Xue, Lu; Zhao, Rongrong; Wang, Lu; Hou, Shuping; Wang, Huiping","year":2021,"journal":"Medical science monitor : international medical journal of experimental and clinical research, 27, e929781","doi":"10.12659/MSM.929781","pmid":"34088889","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"pGP3M treatment significantly reduced IL-17A, IFN-γ, and IL-22 levels in serum compared to IMQ and PBS controls.","whyItMatters":"Understanding how pGP3M works could lead to new treatments for psoriasis, a common inflammatory skin condition. This research highlights the potential of targeting specific proteins to manage autoimmune diseases.","specificNumbers":"","methodology":"Mice were injected with pGP3M or pGP3, and skin lesions were evaluated using a severity index and histological analysis.","limitations":"The study was conducted in mice, and further research is needed to evaluate the safety and efficacy in humans."},{"rthcId":"RPEP-05934","title":"Engineering of highly potent and selective HNTX-III mutant against hNav1.7 sodium channel for treatment of pain.","authors":"Zhang, Yunxiao; Wang, Li; Peng, Dezheng; Zhang, Qingfeng; Yang, Qiuchu; Li, Jiayan; Li, Dan; Tang, Dongfang; Chen, Minzhi; Liang, Songping; Liu, Yu; Wang, Sheng; Liu, Zhonghua","year":2021,"journal":"The Journal of biological chemistry, 296, 100326","doi":"10.1016/j.jbc.2021.100326","pmid":"33493520","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The engineered peptide H4 showed a 30-fold improved potency (IC50 0.007 ± 0.001 μM) and >1000-fold selectivity against Nav1.4 and Nav1.5.","whyItMatters":"Improving the potency and selectivity of pain-targeting compounds can lead to more effective treatments with fewer side effects. This research could pave the way for new analgesics that specifically target pain pathways.","specificNumbers":"","methodology":"The study utilized alanine scanning mutagenesis, site-directed mutagenesis, and molecular docking to identify and enhance the peptide's interaction with the hNav1.7 channel.","limitations":"The study primarily focuses on in vitro and animal models, which may not fully translate to human applications."},{"rthcId":"RPEP-05935","title":"Updated Role of Neuropeptide Y in Nicotine-Induced Endothelial Dysfunction and Atherosclerosis.","authors":"Zheng, Yan-Li; Wang, Wan-da; Li, Mei-Mei; Lin, Shu; Lin, Hui-Li","year":2021,"journal":"Frontiers in cardiovascular medicine, 8, 630968","doi":"10.3389/fcvm.2021.630968","pmid":"33708805","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Nicotine increases neuropeptide Y expression, which is linked to endothelial dysfunction.","whyItMatters":"Understanding how nicotine affects blood vessel health is crucial for preventing cardiovascular diseases. Insights into neuropeptide Y's role could lead to new therapeutic strategies.","specificNumbers":"","methodology":"This is a review study that synthesizes existing research on nicotine, neuropeptide Y, and endothelial dysfunction.","limitations":"As a review, this study does not provide new experimental data, and its conclusions rely on existing literature."},{"rthcId":"RPEP-05936","title":"Pharmacokinetics and tissue distribution study of 18 bioactive components in healthy and chronic heart failure rats after oral administration of Qi-Shen-Ke-Li formula using ultra-high-performance liquid chromatography/triple quadrupole mass spectrometry.","authors":"Zhou, Hui; He, Yang; Zheng, Zhong; Xing, Junpeng; Liu, Zhiqiang; Pi, Zifeng; Liu, Shu","year":2021,"journal":"Rapid communications in mass spectrometry : RCM, 35(8), e9060","doi":"10.1002/rcm.9060","pmid":"33527517","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In CHF rats, the bioavailability of eight compounds in the liver was enhanced.","whyItMatters":"Understanding how QSKL behaves in CHF conditions can inform its clinical use and safety. This research may lead to better treatment strategies for heart failure.","specificNumbers":"","methodology":"The study induced CHF in rats and analyzed the pharmacokinetics and tissue distribution of QSKL using UHPLC/TQ-MS.","limitations":"The study was conducted in rats, and results may not directly translate to humans. Further clinical studies are needed."},{"rthcId":"RPEP-05937","title":"Scavenger receptor B1 mediates phagocytosis and the antimicrobial peptide pathway in the endoparasitic wasp Micropilits mediator.","authors":"Zhou, Li-Zhen; Wang, Rui-Juan; Yan, You-Ying; Zeng, Shuocheng; Zou, Zhen; Lu, Zhiqiang","year":2021,"journal":"Developmental and comparative immunology, 119, 104039","doi":"10.1016/j.dci.2021.104039","pmid":"33549640","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Knockdown of MmSR-B1 increased wasp mortality when challenged by bacteria.","whyItMatters":"Understanding how insects like wasps fight infections can provide insights into immune system evolution and potential applications in pest control.","specificNumbers":"","methodology":"The study involved recombinant protein production, RNA interference for gene knockdown, and assays to measure phagocytosis and immune response.","limitations":"The study focuses on a single species and may not represent all wasps or insects."},{"rthcId":"RPEP-05938","title":"Context contribution to the intermolecular recognition of human ACE2-derived peptides by SARS-CoV-2 spike protein: implications for improving the peptide affinity but not altering the peptide specificity by optimizing indirect readout.","authors":"Zhou, Peng; Wang, Heyi; Chen, Zheng; Liu, Qian","year":2021,"journal":"Molecular omics, 17(1), 86-94","doi":"10.1039/d0mo00103a","pmid":"33174576","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Peptide modifications improved binding affinity to the spike protein without altering specificity.","whyItMatters":"Understanding peptide interactions with the SARS-CoV-2 spike protein can inform the development of effective treatments for COVID-19.","specificNumbers":"","methodology":"The study utilized energetic analysis and dynamics simulations to assess peptide binding and structural context.","limitations":"The study primarily focuses on in vitro analysis, which may not fully represent in vivo conditions."},{"rthcId":"RPEP-05939","title":"Changes in bacterial community and expression of genes involved in intestinal innate immunity in the jejunum of newborn lambs during the first 24 hours of life.","authors":"Zhu, H L; Zhao, X W; Han, R W; DU, Q J; Qi, Y X; Jiang, H N; Huang, D W; Yang, Y X","year":2021,"journal":"Journal of dairy science, 104(8), 9263-9275","doi":"10.3168/jds.2020-19888","pmid":"33985780","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Colostrum intake led to increased expression of immune-related genes and changes in gut bacteria within 24 hours.","whyItMatters":"Understanding how colostrum influences gut health can improve management practices for newborn ruminants, potentially enhancing their survival and growth.","specificNumbers":"","methodology":"The study involved 27 newborn lambs, with some fed colostrum and others not, followed by tissue sampling and analysis of bacterial profiles and gene expression.","limitations":"The study was limited to lambs and may not directly apply to other species; also, the sample size was relatively small."},{"rthcId":"RPEP-05940","title":"Expression and purification of the native C-amidated antimicrobial peptide maculatin 1.1.","authors":"Zhu, Shiying; Weber, Daniel K; Separovic, Frances; Sani, Marc-Antoine","year":2021,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 27(8), e3330","doi":"10.1002/psc.3330","pmid":"33843136","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The study produced 0.1 mg/L of isotopically enriched Mac1 with identical structure and activity to the synthetically made version.","whyItMatters":"Understanding and producing antimicrobial peptides like Mac1 can lead to new treatments for bacterial infections, especially as antibiotic resistance rises.","specificNumbers":"","methodology":"The researchers used a recombinant expression protocol with a double-fusion construct to produce Maculatin 1.1 in E. coli.","limitations":"The study was conducted in vitro, and results may not directly translate to in vivo conditions in humans."},{"rthcId":"RPEP-05941","title":"Pan-coronavirus fusion inhibitors possess potent inhibitory activity against HIV-1, HIV-2, and simian immunodeficiency virus.","authors":"Zhu, Yun; Yu, Danwei; Yan, Hongliang; Chong, Huihui; He, Yuxian","year":2021,"journal":"Emerging microbes & infections, 10(1), 810-821","doi":"10.1080/22221751.2021.1917309","pmid":"33847245","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05942","title":"Thymosin beta 4 alleviates non-alcoholic fatty liver by inhibiting ferroptosis via up-regulation of GPX4.","authors":"Zhu, Zixin; Zhang, Ya; Huang, Xinhao; Can, Li; Zhao, Xueke; Wang, Yinghui; Xue, Jing; Cheng, Mingliang; Zhu, Lili","year":2021,"journal":"European journal of pharmacology, 908, 174351","doi":"10.1016/j.ejphar.2021.174351","pmid":"34280397","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tβ4 improved liver health by inhibiting ferroptosis and up-regulating GPX4.","whyItMatters":"Understanding how Tβ4 works could lead to new treatments for NAFLD, a growing health concern worldwide. This research highlights the potential of targeting ferroptosis in liver diseases.","specificNumbers":"","methodology":"The study used a rat model of NAFLD induced by a high-fat diet, along with in vitro experiments on liver cells.","limitations":"The study was conducted in rats and liver cells, which may not fully represent human responses."},{"rthcId":"RPEP-05943","title":"Comparative Cardio-Renal Outcomes of Type 2 Diabetes Patients Administered Glucagon-Like Peptide-1 Receptor Agonists: A Network Meta-Analysis.","authors":"Zhuo, Chuanjun; Lin, Chongguang; Zhou, Chunhua; Gao, Xiangyang; Shao, Hailin; Fang, Tao; Tian, Hongjun; Ding, Li; Liu, Ming","year":2021,"journal":"Frontiers in pharmacology, 12, 759262","doi":"10.3389/fphar.2021.759262","pmid":"35002700","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Oral semaglutide ranked highest for cardiovascular and kidney outcomes among GLP-1 RAs.","whyItMatters":"Understanding the comparative effectiveness of diabetes treatments can help healthcare providers make informed decisions. This research highlights the potential benefits of oral semaglutide for patients with type 2 diabetes.","specificNumbers":"","methodology":"A systematic review and network meta-analysis of randomized controlled trials was conducted.","limitations":"The analysis is based on existing trials, which may have variability in design and patient populations."},{"rthcId":"RPEP-05944","title":"Enterotoxigenic Escherichia coli infection promotes enteric defensin expression via FOXO6-METTL3-m6A-GPR161 signalling axis.","authors":"Zong, Xin; Wang, Hong; Xiao, Xiao; Zhang, Yu; Hu, Yuhan; Wang, Fengqin; Wang, Yizhen; Lu, Zeqing","year":2021,"journal":"RNA biology, 18(4), 576-586","doi":"10.1080/15476286.2020.1820193","pmid":"32914682","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"E. coli K88 infection increases β-defensin production via METTL3 and FOXO6 interaction.","whyItMatters":"Understanding how defensins are regulated during bacterial infections can inform new strategies for enhancing innate immunity. This knowledge may lead to better treatments for infections caused by E. coli and similar pathogens.","specificNumbers":"","methodology":"The study utilized MeRIP-seq to analyze mRNA modifications and their effects on defensin expression.","limitations":"The study primarily focuses on a specific bacterial strain and may not account for variations in other strains or conditions."},{"rthcId":"RPEP-05945","title":"Impact of injection sites on clinical pharmacokinetics of subcutaneously administered peptides and proteins.","authors":"Zou, Peng; Wang, Fuyuan; Wang, Jie; Lu, Yanhui; Tran, Doanh; Seo, Shirley K","year":2021,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 336, 310-321","doi":"10.1016/j.jconrel.2021.06.038","pmid":"34186147","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05946","title":"Bioactive scaffolds with enhanced supramolecular motion promote recovery from spinal cord injury.","authors":"Álvarez, Z; Kolberg-Edelbrock, A N; Sasselli, I R; Ortega, J A; Qiu, R; Syrgiannis, Z; Mirau, P A; Chen, F; Chin, S M; Weigand, S; Kiskinis, E; Stupp, S I","year":2021,"journal":"Science (New York, N.Y.), 374(6569), 848-856","doi":"10.1126/science.abh3602","pmid":"34762454","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05947","title":"Codd 2022 Telomere Mr Cvd","authors":"","year":2022,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05948","title":"Ilina 2022 Neuroepigenetic Mechanisms Of Action","authors":"","year":2022,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05949","title":"Khoo 2022 Orexin Drug Addiction Translational","authors":"","year":2022,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05950","title":"Kirsch 2022 Minimally Invasive Sustainedrelease Relaxin","authors":"","year":2022,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05951","title":"Matzeu 2022 Suvorexant Cocaine Hedonic","authors":"","year":2022,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05952","title":"Mccartney 2022 Epigenetic Clocks Comparison","authors":"","year":2022,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05953","title":"Mortazavi 2022 Skin Permeability A Dismissed","authors":"","year":2022,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05954","title":"Phetsouphanh 2022 Long Covid T Cell Dysregulation","authors":"","year":2022,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05955","title":"Wang 2022 Gsh Gradient Tumor Linker Design","authors":"","year":2022,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05956","title":"Insulin-like peptide 3 (INSL3) in congenital hypogonadotrophic hypogonadism (CHH) in boys with delayed puberty and adult men.","authors":"Abbara, Ali; Koysombat, Kanyada; Phylactou, Maria; Eng, Pei Chia; Clarke, Sophie; Comninos, Alexander N; Yang, Lisa; Izzi-Engbeaya, Chioma; Hanassab, Simon; Smith, Neil; Jayasena, Channa N; Xu, Cheng; Quinton, Richard; Pitteloud, Nelly; Binder, Gerhard; Anand-Ivell, Ravinder; Ivell, Richard; Dhillo, Waljit S","year":2022,"journal":"Frontiers in endocrinology, 13, 1076984","doi":"10.3389/fendo.2022.1076984","pmid":"36523592","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Median INSL3 was 0.35 ng/ml in boys with CDGP vs 0.15 ng/ml in CHH (p=0.0002).","whyItMatters":"Identifying the cause of delayed puberty is crucial for appropriate treatment. This study highlights the potential of INSL3 as a diagnostic marker.","specificNumbers":"","methodology":"The study involved retrospective cohort analysis of 60 boys and 44 adult men, measuring INSL3, inhibin B, testosterone, and gonadotrophins.","limitations":"The study is retrospective and may not account for all variables affecting hormone levels."},{"rthcId":"RPEP-05957","title":"Self-assembly and Hydrogelation Properties of Peptides Derived from Peptic Cleavage of Aggregation-prone Regions of Ovalbumin.","authors":"Abioye, Raliat O; Acquah, Caleb; Hsu, Pei Chun Queenie; Hüttmann, Nico; Sun, Xiaohong; Udenigwe, Chibuike C","year":2022,"journal":"Gels (Basel, Switzerland), 8(10)","doi":"10.3390/gels8100641","pmid":"36286142","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Peptides from egg white formed aggregates with significant hydrogelation properties after 16 hours.","whyItMatters":"Understanding how food proteins can form gels opens up new possibilities for their use in food and biomedical materials. This research could lead to innovative applications in food technology and material science.","specificNumbers":"","methodology":"The study involved incubating egg white protein hydrolysates generated by pepsin for 16 hours to observe self-assembly and hydrogelation.","limitations":"The study primarily focuses on egg white proteins, and results may not be generalizable to other protein sources."},{"rthcId":"RPEP-05958","title":"Oral delivery of systemic monoclonal antibodies, peptides and small molecules using gastric auto-injectors.","authors":"Abramson, Alex; Frederiksen, Morten Revsgaard; Vegge, Andreas; Jensen, Brian; Poulsen, Mette; Mouridsen, Brian; Jespersen, Mikkel Oliver; Kirk, Rikke Kaae; Windum, Jesper; Hubálek, František; Water, Jorrit J; Fels, Johannes; Gunnarsson, Stefán B; Bohr, Adam; Straarup, Ellen Marie; Ley, Mikkel Wennemoes Hvitfeld; Lu, Xiaoya; Wainer, Jacob; Collins, Joy; Tamang, Siddartha; Ishida, Keiko; Hayward, Alison; Herskind, Peter; Buckley, Stephen T; Roxhed, Niclas; Langer, Robert; Rahbek, Ulrik; Traverso, Giovanni","year":2022,"journal":"Nature biotechnology, 40(1), 103-109","doi":"10.1038/s41587-021-01024-0","pmid":"34462588","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The gastric auto-injector capsule achieved remarkable drug delivery performance in swine:\n\n• Up to 80% absolute bioavailability — meaning 80% of the drug reached the bloodstream, comparable to injection\n• Maximum plasma concentration reached within 30 minutes of oral dosing\n• Capable of delivering up to 4 mg doses per capsule\n• Performance was 10× better than previous injector capsule designs and up to 100× better than chemical permeation enhancement technologies\n• Successfully delivered four different drug classes: adalimumab (monoclonal antibody), a GLP-1 analog (peptide), recombinant human insulin (peptide), and epinephrine (small molecule)\n• Multi-day dosing experiments in awake animals demonstrated consistent performance and translational potential","whyItMatters":"Millions of people inject peptide drugs daily or weekly — insulin for diabetes, GLP-1 agonists for obesity, adalimumab for autoimmune conditions. Needle fear, injection burden, and the need for cold-chain storage are major barriers to treatment adherence. A capsule that achieves injection-like bioavailability could transform how these drugs are delivered, making treatment simpler and more accessible for patients worldwide.","specificNumbers":"","methodology":"Researchers designed an orally administered liquid auto-injector capsule and tested it in swine (pigs), which have gastrointestinal anatomy similar to humans. They measured bioavailability, pharmacokinetics (how quickly drugs reached peak blood levels), and dosing consistency across multiple days. Four clinically relevant injectable medications were tested: adalimumab, a GLP-1 analog, recombinant human insulin, and epinephrine. Both sedated and awake animal models were used.","limitations":"All experiments were conducted in pigs, not humans. While swine GI anatomy is similar to humans, translation to clinical use requires human safety and efficacy trials. The long-term safety of repeated stomach wall injections is unknown. The capsule's size, manufacturing scalability, and cost are not discussed. Patient acceptability of swallowing an auto-injecting capsule has not been studied."},{"rthcId":"RPEP-05959","title":"Proteomics Characterization of Food-Derived Bioactive Peptides with Anti-Allergic and Anti-Inflammatory Properties.","authors":"Abril, Ana G; Pazos, Manuel; Villa, Tomás G; Calo-Mata, Pilar; Barros-Velázquez, Jorge; Carrera, Mónica","year":2022,"journal":"Nutrients, 14(20)","doi":"10.3390/nu14204400","pmid":"36297084","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Food-derived bioactive peptides can provide anti-allergic and anti-inflammatory benefits.","whyItMatters":"Understanding these peptides could lead to safer treatments for allergies and inflammation, reducing reliance on conventional drugs.","specificNumbers":"","methodology":"The study utilized proteomics, particularly high-resolution mass spectrometry, to identify and characterize bioactive peptides.","limitations":"The review does not include experimental data or clinical trials to support the findings."},{"rthcId":"RPEP-05960","title":"Evolution of Potential Antimitotic Stapled Peptides from Multiple Helical Peptide Stretches of the Tubulin Heterodimer Interface: Helix-Mimicking Stapled Peptide Tubulin Inhibitors.","authors":"Adak, Anindyasundar; Das, Gaurav; Gupta, Varsha; Khan, Juhee; Mukherjee, Nabanita; Mondal, Prasenjit; Roy, Rajsekhar; Barman, Surajit; Gharai, Prabir Kumar; Ghosh, Surajit","year":2022,"journal":"Journal of medicinal chemistry, 65(20), 13866-13878","doi":"10.1021/acs.jmedchem.2c01116","pmid":"36240440","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The para-fluorophenylalanine-modified stapled peptide was identified as the most potent inhibitor, affecting microtubule dynamics and inducing apoptosis.","whyItMatters":"Targeting tubulin interactions is a promising strategy for developing new cancer therapies. The findings could lead to more effective treatments for melanoma and other cancers.","specificNumbers":"","methodology":"The researchers designed stapled analogues of helical peptide sequences and tested their effects on tubulin interactions and cancer cell growth.","limitations":"The study primarily focuses on in vitro results, which may not fully translate to in vivo effectiveness in humans."},{"rthcId":"RPEP-05961","title":"Antimicrobial Peptides in Early-Life Host Defense, Perinatal Infections, and Necrotizing Enterocolitis-An Update.","authors":"Agakidou, Eleni; Agakidis, Charalampos; Kontou, Angeliki; Chotas, William; Sarafidis, Kosmas","year":2022,"journal":"Journal of clinical medicine, 11(17)","doi":"10.3390/jcm11175074","pmid":"36079001","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"AMPs are linked to the severity of chorioamnionitis, neonatal sepsis, and NEC.","whyItMatters":"Understanding AMPs can lead to better diagnostic and treatment options for newborn infections, especially in light of rising antibiotic resistance.","specificNumbers":"","methodology":"The study is a review of existing literature on antimicrobial peptides and their roles in early-life infections.","limitations":"Limited studies on AMP expression levels in fetuses and neonates restrict comprehensive understanding."},{"rthcId":"RPEP-05962","title":"Antiviral Peptides as Anti-Influenza Agents.","authors":"Agamennone, Mariangela; Fantacuzzi, Marialuigia; Vivenzio, Giovanni; Scala, Maria Carmina; Campiglia, Pietro; Superti, Fabiana; Sala, Marina","year":2022,"journal":"International journal of molecular sciences, 23(19)","doi":"10.3390/ijms231911433","pmid":"36232735","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05963","title":"Biologically Active Peptides from Venoms: Applications in Antibiotic Resistance, Cancer, and Beyond.","authors":"Ageitos, Lucía; Torres, Marcelo D T; de la Fuente-Nunez, Cesar","year":2022,"journal":"International journal of molecular sciences, 23(23)","doi":"10.3390/ijms232315437","pmid":"36499761","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Venom-derived peptides from South American organisms have diverse biological activities.","whyItMatters":"Understanding venom peptides can lead to new therapies for diseases that are difficult to treat, such as antibiotic-resistant infections and cancer.","specificNumbers":"","methodology":"This is a review study summarizing existing research on venom-derived peptides.","limitations":"As a review, it does not present new experimental data but summarizes existing literature."},{"rthcId":"RPEP-05964","title":"Comparison of ANP and BNP Granular Density in Atria of Rats After Physiological and Pathological Hypertrophy.","authors":"Agostinucci, Kevin; Manfredi, Thomas G; Cosmas, Arthur C; Vetter, Frederick J; Engle, Steven K","year":2022,"journal":"Toxicologic pathology, 50(4), 497-506","doi":"10.1177/01926233221097970","pmid":"35608026","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Both treatments increased heart weight by 15%, with drug treatment increasing BNP density in right atria.","whyItMatters":"Understanding how these hormones change can help in diagnosing and treating heart conditions. The findings may provide new insights into differentiating between healthy and unhealthy heart growth.","specificNumbers":"","methodology":"The study used immunoelectron microscopy to analyze atrial granules in Sprague Dawley rats after 28 days of chronic swim exercise or PPARγ agonist treatment.","limitations":"The study was conducted in rats, so results may not directly apply to humans. Additionally, the long-term effects of these treatments were not assessed."},{"rthcId":"RPEP-05965","title":"An injectable self-assembling hydrogel based on RGD peptidomimetic β-sheets as multifunctional biomaterials.","authors":"Ahmadi, Zeba; Yadav, Santosh; Kar, Aditya Kumar; Jha, Diksha; Gautam, Hemant Kumar; Patnaik, Satyakam; Kumar, Pradeep; Sharma, Ashwani Kumar","year":2022,"journal":"Biomaterials advances, 133, 112633","doi":"10.1016/j.msec.2021.112633","pmid":"35527136","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The new RGD mimetic peptides showed enhanced cell adhesion and antimicrobial activity against resistant pathogens.","whyItMatters":"These findings could lead to more effective materials for tissue engineering, potentially improving patient outcomes in regenerative medicine.","specificNumbers":"","methodology":"The study involved synthesizing modified RGD peptides, characterizing their properties, and testing their performance in cell adhesion and antimicrobial activity.","limitations":"The study primarily focuses on in vitro results; further in vivo studies are needed to confirm efficacy in living organisms."},{"rthcId":"RPEP-05966","title":"Role of Thymosin Beta 4 in the diagnosis of Nonalcoholic Fatty Liver and its relation to Metabolic Syndrome in Egyptian patients.","authors":"Ahmed, Ahmed E; Ibrahim, Wesam A; Nabil, Zeinab M; Mansour, Khaled A; Mansour, Ahmed M F; ElGhandour, Ahmed M","year":2022,"journal":"The Egyptian journal of immunology, 29(2), 76-86","doi":null,"pmid":"35436057","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Serum Tβ4 had 100% sensitivity and specificity for predicting NAFLD at ≤900 ng/ml.","whyItMatters":"Identifying reliable non-invasive biomarkers like Tβ4 could improve NAFLD diagnosis and management, reducing the need for invasive procedures like liver biopsies.","specificNumbers":"","methodology":"The study involved 80 patients divided into two groups: 40 with NAFLD and 40 controls, with assessments including physical exams and laboratory tests.","limitations":"The study was limited to a specific population in Egypt, which may affect the generalizability of the findings."},{"rthcId":"RPEP-05967","title":"Role of Calcitonin Gene-Related Peptide on the Gastrointestinal Symptoms of Migraine-Clinical Considerations: A Narrative Review.","authors":"Ailani, Jessica; Kaiser, Eric A; Mathew, Paul G; McAllister, Peter; Russo, Andrew F; Vélez, Christopher; Ramajo, Angela Pozo; Abdrabboh, Ahmad; Xu, Cen; Rasmussen, Soeren; Tepper, Stewart J","year":2022,"journal":"Neurology, 99(19), 841-853","doi":"10.1212/WNL.0000000000201332","pmid":"36127137","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CGRP is associated with gastrointestinal symptoms like nausea in migraine patients.","whyItMatters":"Understanding the role of CGRP can help improve treatment strategies for migraine patients experiencing gastrointestinal issues. This could enhance patient care and quality of life.","specificNumbers":"","methodology":"This study is a narrative review summarizing existing literature on CGRP and its effects on gastrointestinal symptoms in migraine.","limitations":"As a narrative review, it may not include all relevant studies or provide comprehensive data analysis."},{"rthcId":"RPEP-05968","title":"Use of kefir peptide (Kef-1) as an emerging approach for the treatment of oxidative stress and inflammation in 2K1C mice.","authors":"Aires, Rafaela; Gobbi Amorim, Fernanda; Côco, Larissa Zambom; da Conceição, Amanda Pompermayer; Zanardo, Tadeu Ériton Caliman; Taufner, Gabriel Henrique; Nogueira, Breno Valentim; Vasquez, Elisardo Corral; Melo Costa Pereira, Thiago; Campagnaro, Bianca Prandi; Dos Santos Meyrelles, Silvana","year":2022,"journal":"Food & function, 13(4), 1965-1974","doi":"10.1039/d1fo01798e","pmid":"35088783","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Kef-1 peptide reduced ROS production and improved vascular structure in 2K1C mice.","whyItMatters":"Understanding how Kef-1 works could lead to new treatments for hypertension and related cardiovascular diseases. This research highlights the potential of natural compounds in managing health conditions.","specificNumbers":"","methodology":"The study used an angiotensin II-dependent hypertension model in 2K1C mice to evaluate the effects of Kef-1.","limitations":"The study was conducted in mice, and results may not directly translate to humans. Further research is needed to confirm efficacy in human populations."},{"rthcId":"RPEP-05969","title":"Fast killing kinetics, significant therapeutic index, and high stability of melittin-derived antimicrobial peptide.","authors":"Akbari, Reza; Hakemi Vala, Mojdeh; Sabatier, Jean-Marc; Pooshang Bagheri, Kamran","year":2022,"journal":"Amino acids, 54(9), 1275-1285","doi":"10.1007/s00726-022-03180-2","pmid":"35779173","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"MDP1 and MDP2 are 252- and 132-fold more therapeutically effective than melittin.","whyItMatters":"With the rise of drug-resistant bacteria, new antimicrobial agents like MDP1 and MDP2 are crucial for effective treatment. Their low toxicity and high stability make them promising candidates for further development.","specificNumbers":"","methodology":"The study evaluated the killing kinetics, toxicity, and stability of MDP1 and MDP2, along with structural analysis.","limitations":"The study primarily focuses on in vitro results, and further research is needed to confirm efficacy in vivo."},{"rthcId":"RPEP-05970","title":"Self-Assembled Peptide Habitats to Model Tumor Metastasis.","authors":"Al Balushi, Noora; Boyd-Moss, Mitchell; Samarasinghe, Rasika M; Rifai, Aaqil; Franks, Stephanie J; Firipis, Kate; Long, Benjamin M; Darby, Ian A; Nisbet, David R; Pouniotis, Dodie; Williams, Richard J","year":2022,"journal":"Gels (Basel, Switzerland), 8(6)","doi":"10.3390/gels8060332","pmid":"35735676","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The 3D peptide scaffold improved the growth and migration of multicellular lung tumor spheroids.","whyItMatters":"This research could lead to better cancer models that reflect real tumor behavior, potentially improving treatment strategies. Understanding tumor microenvironments is crucial for developing effective therapies.","specificNumbers":"","methodology":"The study utilized a novel matrix of functionally programmed peptide sequences to create a self-assembled scaffold for tumor cell growth.","limitations":"The study is a proof-of-concept and may require further validation in more complex biological systems."},{"rthcId":"RPEP-05971","title":"Reduced vitamin D-induced cathelicidin production and killing of Mycobacterium tuberculosis in macrophages from a patient with a non-functional vitamin D receptor: A case report.","authors":"Al-Jaberi, Fatima A H; Crone, Cornelia Geisler; Lindenstrøm, Thomas; Arildsen, Nicolai Skovbjerg; Lindeløv, Emilia Sæderup; Aagaard, Louise; Gravesen, Eva; Mortensen, Rasmus; Andersen, Aase Bengaard; Olgaard, Klaus; Hjaltelin, Jessica Xin; Brunak, Søren; Bonefeld, Charlotte Menné; Kongsbak-Wismann, Martin; Geisler, Carsten","year":2022,"journal":"Frontiers in immunology, 13, 1038960","doi":"10.3389/fimmu.2022.1038960","pmid":"36405761","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The patient's macrophages showed significantly reduced cathelicidin production, impairing their ability to combat M. tuberculosis.","whyItMatters":"Understanding how vitamin D influences immune responses can lead to better strategies for preventing and treating tuberculosis, especially in vulnerable populations.","specificNumbers":"","methodology":"The study involved analyzing macrophages from a patient with hereditary vitamin D-resistant rickets to assess cathelicidin production.","limitations":"The findings are based on a single case study, limiting the generalizability of the results."},{"rthcId":"RPEP-05972","title":"Targeting and Modulation of the Natriuretic Peptide System in Covid-19: A Single or Double-Edged Effect?","authors":"Al-Kuraishy, Hayder M; Al-Gareeb, Ali I; Alexiou, Athanasios; Batiha, Gaber El-Saber","year":2022,"journal":"Current protein & peptide science, 23(5), 321-334","doi":"10.2174/1389203723666220628114928","pmid":"35762551","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Natriuretic peptides have protective effects against acute lung injury in Covid-19 but neprilysin inhibitors may also increase harmful pro-inflammatory cytokines.","whyItMatters":"Understanding the dual role of natriuretic peptides in Covid-19 could inform treatment strategies and improve patient outcomes. It highlights the need for careful consideration of neprilysin inhibitors in clinical settings.","specificNumbers":"","methodology":"The study reviews the physiological effects of natriuretic peptides and their interactions with neprilysin in the context of Covid-19.","limitations":"The study primarily reviews existing literature without new experimental data, limiting the ability to draw definitive conclusions."},{"rthcId":"RPEP-05973","title":"Nose-to-Brain Delivery of Therapeutic Peptides as Nasal Aerosols.","authors":"Alabsi, Wafaa; Eedara, Basanth Babu; Encinas-Basurto, David; Polt, Robin; Mansour, Heidi M","year":2022,"journal":"Pharmaceutics, 14(9)","doi":"10.3390/pharmaceutics14091870","pmid":"36145618","tags":["intranasal-delivery","blood-brain-barrier","peptide-delivery"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Nose-to-brain (N-to-B) delivery offers a non-invasive way to get peptide drugs into the brain by bypassing the blood-brain barrier entirely. The olfactory and trigeminal nerves provide direct pathways from the nasal cavity to the brain, allowing peptide drugs to reach the CNS without needing injections or having to survive the digestive system. This approach can rapidly target the brain while minimizing systemic exposure and side effects. The review covers clinical applications, nasal delivery devices, and the current limitations of this approach.","whyItMatters":"The blood-brain barrier blocks over 98% of potential drugs from reaching the brain, making brain diseases among the hardest to treat. Peptides are particularly promising for neurological conditions due to their specificity and low toxicity, but they can't cross the BBB or survive oral delivery. Nose-to-brain delivery solves both problems at once — getting peptides to the brain without surgery, injections, or the digestive tract. This could transform treatment for Alzheimer's, Parkinson's, depression, chronic pain, and brain tumors.","specificNumbers":"Routes: olfactory nerve + trigeminal nerve pathways · Bypasses BBB · Minimizes systemic exposure · Non-invasive alternative to injection · Applications: psychiatric disorders, neurodegeneration, pain, stroke, brain tumors","methodology":"Narrative review of published literature on intranasal peptide delivery, covering the anatomy and physiology of nose-to-brain transport, formulation strategies, clinical applications across CNS diseases, nasal delivery devices, and the limitations and challenges of the approach.","limitations":"The review is broad and does not present original data. While the concept of nose-to-brain delivery is well-established, many applications are still in early research stages. Challenges include variable absorption depending on nasal anatomy and health, limited dose volumes, mucociliary clearance that removes drugs, and difficulty controlling dosing precision. Translation from animal models (especially rodents, which have proportionally larger olfactory regions) to humans has been inconsistent."},{"rthcId":"RPEP-05974","title":"Effects of bioactive peptides derived from feather keratin on plasma cholesterol level, lipid oxidation of meat, and performance of broiler chicks.","authors":"Alahyaribeik, Samira; Nazarpour, Madineh; Tabandeh, Fatemeh; Honarbakhsh, Shirin; Sharifi, Seyed Davood","year":2022,"journal":"Tropical animal health and production, 54(5), 271","doi":"10.1007/s11250-022-03244-1","pmid":"36040617","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Chicks receiving feather peptides had greater weight gain and lower cholesterol levels.","whyItMatters":"This research suggests that bioactive peptides from feathers can enhance poultry health and meat quality, which could benefit the poultry industry.","specificNumbers":"","methodology":"The study involved 80 day-old male broiler chicks divided into two groups, one receiving water with 50 mg/L of mixed feather bioactive peptides and the other receiving plain water.","limitations":"The study was limited to a specific breed of broiler chicks and may not be applicable to all poultry types."},{"rthcId":"RPEP-05975","title":"Could the New Anti-CGRP Monoclonal Antibodies Be Effective in Migraine Aura? Case Reports and Literature Review.","authors":"Albanese, Maria; Mercuri, Nicola Biagio","year":2022,"journal":"Journal of clinical medicine, 11(5)","doi":"10.3390/jcm11051228","pmid":"35268319","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Two patients with migraine with aura reported striking improvements in their aura symptoms while taking anti-CGRP antibodies. One patient on galcanezumab experienced complete disappearance of aura, while another on erenumab had reduced aura duration and intensity. This is notable because anti-CGRP antibodies are primarily expected to work peripherally (they can't easily cross the blood-brain barrier), yet migraine aura is believed to originate from cortical spreading depression — a brain phenomenon.","whyItMatters":"Migraine aura — visual disturbances, numbness, or speech difficulties before headache — has no specific treatment. Anti-CGRP antibodies were developed to prevent headache, not aura. These cases suggest CGRP may be involved in aura generation, potentially through a peripheral-central connection, and that anti-CGRP drugs might benefit both components of migraine with aura. This raises fundamental questions about how CGRP signaling relates to brain events.","specificNumbers":"n=2 case reports · patient 1: galcanezumab → complete aura disappearance · patient 2: erenumab → reduced aura duration and intensity · 4 anti-CGRP mAbs reviewed (eptinezumab, fremanezumab, galcanezumab, erenumab)","methodology":"Two case reports of migraine with aura patients treated with anti-CGRP monoclonal antibodies (galcanezumab and erenumab), combined with a literature review examining the relationship between cortical spreading depression (CSD) and CGRP, and the potential central mechanisms of peripherally-acting antibodies.","limitations":"Based on only two case reports, the findings are anecdotal and cannot establish efficacy. Placebo effect cannot be ruled out. The mechanism by which peripheral anti-CGRP antibodies might affect central cortical events (aura) remains speculative. Systematic studies of anti-CGRP effects on aura are needed."},{"rthcId":"RPEP-05976","title":"Expression of Antimicrobic Peptide Piscidin1 in Gills Mast Cells of Giant Mudskipper Periophthalmodon schlosseri (Pallas, 1770).","authors":"Alesci, Alessio; Capillo, Gioele; Mokhtar, Doaa M; Fumia, Angelo; D'Angelo, Roberta; Lo Cascio, Patrizia; Albano, Marco; Guerrera, Maria Cristina; Sayed, Ramy K A; Spanò, Nunziacarla; Pergolizzi, Simona; Lauriano, Eugenia Rita","year":2022,"journal":"International journal of molecular sciences, 23(22)","doi":"10.3390/ijms232213707","pmid":"36430187","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Mast cells in the gills of Giant Mudskipper show high positivity for Piscidin1.","whyItMatters":"Understanding how antimicrobial peptides function in fish can inform us about their immune systems and potential applications in aquaculture and conservation.","specificNumbers":"","methodology":"Confocal microscopy was used to assess the expression of Piscidin1 in mast cells of the gills.","limitations":"The study focuses solely on the Giant Mudskipper and may not be generalizable to other species."},{"rthcId":"RPEP-05977","title":"Impact of isoenergetic intake of irregular meal patterns on thermogenesis, glucose metabolism, and appetite: a randomized controlled trial.","authors":"Alhussain, Maha H; Macdonald, Ian A; Taylor, Moira A","year":2022,"journal":"The American journal of clinical nutrition, 115(1), 284-297","doi":"10.1093/ajcn/nqab323","pmid":"34555151","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Thermic effect of food was 97.7 kJ for regular meals vs. 76.7 kJ for irregular meals (P = 0.048).","whyItMatters":"Understanding how meal timing affects metabolism can inform dietary recommendations for weight management, especially for those with insulin resistance.","specificNumbers":"","methodology":"A randomized crossover trial with 9 women who consumed regular and irregular meal patterns over 14 days each, with metabolic measurements taken.","limitations":"The small sample size limits the generalizability of the findings, and the study focused solely on women."},{"rthcId":"RPEP-05978","title":"A state-of-art review on camel milk proteins as an emerging source of bioactive peptides with diverse nutraceutical properties.","authors":"Ali Redha, Ali; Valizadenia, Hamidreza; Siddiqui, Shahida Anusha; Maqsood, Sajid","year":2022,"journal":"Food chemistry, 373(Pt A), 131444","doi":"10.1016/j.foodchem.2021.131444","pmid":"34717085","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Camel milk bioactive peptides exhibit multiple health benefits, including antioxidant and anti-diabetic effects.","whyItMatters":"Understanding the benefits of camel milk peptides could lead to new nutraceutical products. This research highlights the potential for camel milk as a functional food source.","specificNumbers":"","methodology":"The review systematically analyzed 46 research articles focusing on the bioactive properties of camel milk peptides.","limitations":"The review is limited by the lack of in-vivo studies and absence of clinical trials on camel milk bioactive peptides."},{"rthcId":"RPEP-05979","title":"Modulation of Virulence Gene Expression in Salmonella enterica subsp. enterica typhimurium by Synthetic Milk-Derived Peptides.","authors":"Ali, Eman; LaPointe, Gisèle","year":2022,"journal":"Probiotics and antimicrobial proteins, 14(4), 690-698","doi":"10.1007/s12602-022-09936-2","pmid":"35380388","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A mixture of five synthetic peptides significantly downregulated hilA and ssrB gene expressions at 0.02 and 0.2 mg/ml concentrations.","whyItMatters":"Understanding how these peptides can modulate virulence genes may lead to new strategies for preventing Salmonella infections. This could have significant implications for food safety and public health.","specificNumbers":"","methodology":"The study tested five synthetic milk-derived peptides on Salmonella enterica at various concentrations to measure their effects on virulence gene expression.","limitations":"The study was conducted in vitro, meaning results may not directly translate to real-world human applications. Further research is needed to confirm efficacy in living organisms."},{"rthcId":"RPEP-05980","title":"Design of a new cell penetrating peptide for DNA, siRNA and mRNA delivery.","authors":"Ali, Salif; Dussouillez, Candice; Padilla, Beatriz; Frisch, Benoît; Mason, A James; Kichler, Antoine","year":2022,"journal":"The journal of gene medicine, 24(3), e3401","doi":"10.1002/jgm.3401","pmid":"34856643","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"HELP-4H peptide shows high delivery capabilities for plasmid DNA, siRNA, and mRNA.","whyItMatters":"This research could lead to improved methods for delivering genetic therapies, which are crucial for treating various diseases. The ability to function in serum conditions enhances its potential for real-world applications.","specificNumbers":"","methodology":"The study involved modifying the HELP peptide by replacing glutamic acid with histidine to enhance its pH-dependent delivery capabilities, followed by testing its effectiveness in delivering nucleic acids.","limitations":"The study primarily focuses on in vitro results, and further research is needed to confirm effectiveness in vivo."},{"rthcId":"RPEP-05981","title":"The effect of β-caryophyllene on food addiction and its related behaviors: A randomized, double-blind, placebo-controlled trial.","authors":"Alizadeh, Shahab; Djafarian, Kurosh; Mofidi Nejad, Maryam; Yekaninejad, Mir Saeed; Javanbakht, Mohammad Hassan","year":2022,"journal":"Appetite, 178, 106160","doi":"10.1016/j.appet.2022.106160","pmid":"35809704","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"β-caryophyllene (100 mg/day for 8 weeks) significantly reduced Yale Food Addiction Scale scores compared to placebo (change: 1.5 ± 0.9 vs. −0.7 ± 1.4; corrected p=0.05).\n\nSerum orexin-A levels significantly decreased within the β-caryophyllene group (p=0.02), though the between-group comparison did not reach significance after correction (p=0.09). No significant effects were observed on body composition, anthropometric indices, appetite, eating behavior, dietary intake, physical activity, mental health (stress, anxiety, depression), or levels of oxytocin and neuropeptide Y (NPY).","whyItMatters":"Food addiction is increasingly recognized as a contributor to the obesity epidemic, but there are no approved medications for it. β-caryophyllene is a natural, FDA-approved food additive that activates CB2 receptors without the psychoactive effects associated with CB1 activation (the receptor THC targets). The reduction in food addiction scores and orexin-A — a neuropeptide strongly linked to reward-seeking behavior — suggests a novel approach to treating compulsive eating through the cannabinoid-neuropeptide pathway.","specificNumbers":"","methodology":"Randomized, double-blind, placebo-controlled trial. 52 obese women with food addiction (YFAS score ≥3) were randomly assigned to β-caryophyllene softgels (100 mg/day with meal, n=26) or placebo (n=26) for 8 weeks. Outcomes assessed: food addiction scores, body composition, anthropometric measurements, eating behavior, appetite, mental health, dietary intake, physical activity, and serum levels of orexin-A, oxytocin, and neuropeptide Y.","limitations":"Small sample size (52 participants). Women-only, limiting generalizability. The between-group orexin-A comparison did not reach statistical significance after correction (p=0.09). No change in body weight or composition suggests the anti-addiction effect may not translate to meaningful weight loss at this dose and duration. The YFAS score change, while significant, was modest. Only one dose was tested."},{"rthcId":"RPEP-05982","title":"Lunasin as a Promising Plant-Derived Peptide for Cancer Therapy.","authors":"Alves de Souza, Stephanny Miranda; Hernández-Ledesma, Blanca; de Souza, Theo Luiz Ferraz","year":2022,"journal":"International journal of molecular sciences, 23(17)","doi":"10.3390/ijms23179548","pmid":"36076946","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05983","title":"In vitro digestion effect on CCK and GLP-1 release and antioxidant capacity of some plant-based milk substitutes.","authors":"Aly, Esmat; Sánchez-Moya, Teresa; Darwish, Aliaa A; Ros-Berruezo, Gaspar; López-Nicolás, Rubén","year":2022,"journal":"Journal of food science, 87(5), 1999-2008","doi":"10.1111/1750-3841.16140","pmid":"35368090","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Using STC-1 enteroendocrine cells after in vitro digestion:\n\n• GLP-1 release: Spelt milk was highest (910.17 pg/ml), followed closely by cow's milk (876.59 pg/ml), with no significant difference between them\n• CCK release: Cow's milk stimulated significantly more CCK than plant milks overall. Among plant alternatives, tiger nut milk was highest (228.96 pg/ml), followed by hazelnut milk (220.04 pg/ml)\n• Antioxidant capacity: Total phenolic content increased after digestion for all samples. Soymilk had the highest antioxidant values (ORAC: 25.41 µmol TE/ml)\n• Cow's milk and soymilk had the highest post-digestion total phenolic content (165.76 and 153.71 mg GAE/100 ml)","whyItMatters":"As millions of people switch from dairy to plant milks, understanding their effects on satiety hormones is important for weight management and appetite regulation. GLP-1 and CCK are the same peptide hormones targeted by blockbuster obesity drugs. If certain plant milks naturally stimulate these hormones more effectively, they could be promoted as more satiating alternatives for people watching their weight.","specificNumbers":"","methodology":"In vitro study using simulated gastrointestinal digestion followed by exposure to STC-1 enteroendocrine cells (a gut hormone-secreting cell line). CCK and GLP-1 release were measured by ELISA. Antioxidant capacity was assessed using ORAC, FRAP, and ABTS assays. Total phenolic and flavonoid content were measured before and after in vitro digestion. Plant milks tested included tiger nut, hazelnut, spelt, soy, and others, compared to cow's milk.","limitations":"This is entirely an in vitro study — STC-1 cells in a dish do not replicate the complexity of the human gut, where hormonal responses involve neural signaling, microbiome interactions, and gastric emptying. The peptide hormone levels measured in cell culture may not translate to meaningful blood levels or subjective satiety in humans. Only a limited number of plant milks were tested. Commercial plant milk formulations vary widely in composition."},{"rthcId":"RPEP-05984","title":"Efficacy and safety of semaglutide for weight management: evidence from the STEP program.","authors":"Amaro, Anastassia; Sugimoto, Danny; Wharton, Sean","year":2022,"journal":"Postgraduate medicine, 134(sup1), 5-17","doi":"10.1080/00325481.2022.2147326","pmid":"36691309","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide (2.4 mg once weekly) resulted in significant weight loss and improved cardiometabolic factors compared to placebo.","whyItMatters":"With obesity being a major health issue, effective treatments like semaglutide can help manage weight and reduce related health risks. Understanding its safety profile is crucial for healthcare providers.","specificNumbers":"","methodology":"The STEP program included phase 3 trials comparing semaglutide to placebo in adults with obesity, focusing on weight loss and safety.","limitations":"The study primarily focused on short-term outcomes, and long-term effects of semaglutide are still being evaluated."},{"rthcId":"RPEP-05985","title":"Antimicrobial Peptide Analogs From Scorpions: Modifications and Structure-Activity.","authors":"Amorim-Carmo, Bruno; Parente, Adriana M S; Souza, Eden S; Silva-Junior, Arnóbio A; Araújo, Renata M; Fernandes-Pedrosa, Matheus F","year":2022,"journal":"Frontiers in molecular biosciences, 9, 887763","doi":"10.3389/fmolb.2022.887763","pmid":"35712354","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Scorpion AMPs have broad action and potent activity without easily inducing resistance.","whyItMatters":"With rising antibiotic resistance, developing new treatments like scorpion AMPs is crucial for public health. This research could lead to innovative therapies for difficult-to-treat infections.","specificNumbers":"","methodology":"The study is a review that synthesizes existing research on scorpion-derived AMPs and their optimization strategies.","limitations":"The study is a review and does not present new experimental data; practical applications still require extensive testing."},{"rthcId":"RPEP-05986","title":"C-Locked Analogs of the Antimicrobial Peptide BP214.","authors":"Andersen, Ida Kristine Lysgaard; Thomsen, Thomas T; Rashid, Jasmina; Bobak, Thomas Rønnemoes; Oddo, Alberto; Franzyk, Henrik; Løbner-Olesen, Anders; Hansen, Paul R","year":2022,"journal":"Antibiotics (Basel, Switzerland), 11(8)","doi":"10.3390/antibiotics11081080","pmid":"36009951","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Analog 13 showed MIC = 4 µg/mL against E. coli and 36% hemolysis at 150 µM.","whyItMatters":"The findings could lead to new treatments for infections caused by antibiotic-resistant bacteria, which are a growing public health concern.","specificNumbers":"","methodology":"The study involved synthesizing peptide analogs and testing their antimicrobial activity against various bacteria.","limitations":"The study primarily focused on in vitro testing, which may not fully predict effectiveness in humans."},{"rthcId":"RPEP-05987","title":"Bacteriocin-Producing Probiotic Lactic Acid Bacteria in Controlling Dysbiosis of the Gut Microbiota.","authors":"Anjana; Tiwari, Santosh Kumar","year":2022,"journal":"Frontiers in cellular and infection microbiology, 12, 851140","doi":"10.3389/fcimb.2022.851140","pmid":"35651753","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05988","title":"A new era for oral peptides: SNAC and the development of oral semaglutide for the treatment of type 2 diabetes.","authors":"Aroda, Vanita R; Blonde, Lawrence; Pratley, Richard E","year":2022,"journal":"Reviews in endocrine & metabolic disorders, 23(5), 979-994","doi":"10.1007/s11154-022-09735-8","pmid":"35838946","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-05989","title":"Mutant and non-mutant neoantigen-based cancer vaccines: recent advances and future promises.","authors":"Ashi, Mohamad Omar; Mami-Chouaib, Fathia; Corgnac, Stéphanie","year":2022,"journal":"Exploration of targeted anti-tumor therapy, 3(6), 746-762","doi":"10.37349/etat.2022.00111","pmid":"36654823","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"TEIPP derived from non-mutant proteins may effectively target immune-edited tumors.","whyItMatters":"Understanding how to effectively target resistant tumors could lead to better cancer treatments. This research may help improve outcomes for patients who currently do not respond to existing therapies.","specificNumbers":"","methodology":"The study is a review of existing literature on cancer vaccines and immune checkpoint therapies.","limitations":"As a review, it does not present new experimental data and relies on existing studies, which may vary in quality."},{"rthcId":"RPEP-05990","title":"Lactoferrin: An Effective Weapon in the Battle Against Bacterial Infections.","authors":"Avalos-Gómez, Christian; Ramírez-Rico, Gerardo; Ruiz-Mazón, Lucero; Sicairos, Nidia León; Serrano-Luna, Jesús; de la Garza, Mireya","year":2022,"journal":"Current pharmaceutical design, 28(40), 3243-3260","doi":"10.2174/1381612829666221025153216","pmid":"36284379","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Lactoferrin has no known resistance and can enhance the effectiveness of antibiotics.","whyItMatters":"With rising antibiotic resistance, finding effective alternatives like lactoferrin is crucial for public health. It could lead to better treatment strategies for bacterial infections.","specificNumbers":"","methodology":"This is a review study that synthesizes existing research on lactoferrin and its antibacterial properties.","limitations":"The review does not present new experimental data and relies on existing studies, which may vary in quality."},{"rthcId":"RPEP-05991","title":"The Effects of Side-Chain Configurations of a Retro-Inverso-Type Inhibitor on the Human T-Cell Leukemia Virus (HTLV)-1 Protease.","authors":"Awahara, Chiyuki; Oku, Daiki; Furuta, Saki; Kobayashi, Kazuya; Teruya, Kenta; Akaji, Kenichi; Hattori, Yasunao","year":2022,"journal":"Molecules (Basel, Switzerland), 27(5)","doi":"10.3390/molecules27051646","pmid":"35268749","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Retro-inverso (RI) type inhibitors of HTLV-1 protease containing a hydroxyethylamine dipeptide isostere were synthesized with different isoleucine side-chain configurations. Replacing D-Ile with D-allo-Ile in the corresponding substrate positions produced more potent inhibitors.\n\nThe results demonstrated that mimicking the complete topology of the parent inhibitor — both backbone and side-chain spatial arrangements — is critical for designing effective retro-inverso protease inhibitors. Simply reversing the backbone without matching side-chain configurations leads to suboptimal binding.","whyItMatters":"HTLV-1 infects an estimated 5-10 million people worldwide and has no approved antiviral treatment. Protease inhibitors are proven therapies for other retroviruses (like HIV), but developing them for HTLV-1 has lagged behind. This study establishes a design principle — matching full 3D topology, not just backbone — that could accelerate the development of protease-resistant peptide drugs for HTLV-1 and other targets.","specificNumbers":"","methodology":"The researchers first examined how different isoleucine side-chain configurations in substrate peptides affected HTLV-1 protease activity. Based on these findings, they synthesized RI-type inhibitors using Fmoc-based solid-phase peptide synthesis, incorporating D-allo-Ile where appropriate. Inhibitory activity was evaluated against refolded recombinant HTLV-1 protease (1-116, L40I).","limitations":"All experiments were conducted in vitro using recombinant protease. The inhibitors' stability, cell penetration, antiviral activity in cell culture, and in vivo pharmacokinetics were not assessed. The L40I protease variant used may have slightly different properties than wild-type. The structure-activity relationships may not generalize to all retro-inverso peptide designs."},{"rthcId":"RPEP-05992","title":"Effects of sesame meal bioactive peptides, individually or in combination with a mixture of essential oils, on growth performance, carcass, jejunal morphology, and microbial composition of broiler chickens.","authors":"Bahadori, Mohammad Mehdi; Rezaeipour, Vahid; Abdullahpour, Rohullah; Irani, Mehrdad","year":2022,"journal":"Tropical animal health and production, 54(4), 235","doi":"10.1007/s11250-022-03232-5","pmid":"35859053","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Chickens fed a diet with SMBP and essential oils showed improved weight gain and better gut health.","whyItMatters":"Improving growth performance and gut health in poultry can lead to better meat production and animal welfare. This research may help optimize poultry diets.","specificNumbers":"","methodology":"The study involved 250 male Ross broiler chicks divided into five dietary treatment groups over a specific feeding period.","limitations":"The study focused only on male broiler chickens and may not apply to other poultry types or genders."},{"rthcId":"RPEP-05993","title":"Value of Thymosin α1 Combined With Blood Purification to Increase Successful Rescues of Shock Patients.","authors":"Bai, Ling; Qiu, Xiaojuan; Ding, Xinai; Bai, Xiaoyan; Huang, Wan; Yang, Likun; Shi, Xiaoyan","year":2022,"journal":"Alternative therapies in health and medicine, 28(7), 146-152","doi":null,"pmid":"35951068","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The intervention group had a significantly shorter duration of shock and ICU stay, with a higher overall response rate (P < .05).","whyItMatters":"Improving treatment outcomes for septic shock patients can significantly reduce mortality rates and enhance recovery. This study suggests a promising combination therapy that may lead to better patient management in critical care settings.","specificNumbers":"","methodology":"A randomized controlled trial involving 86 septic shock patients assigned to either T-α1 plus BP or BP only.","limitations":"The study was limited to a single hospital and may not account for variations in treatment protocols elsewhere."},{"rthcId":"RPEP-05994","title":"Aluminum nanoparticles deliver a dual-epitope peptide for enhanced anti-tumor immunotherapy.","authors":"Bai, Shuting; Jiang, Hao; Song, Yuanshuai; Zhu, Yining; Qin, Ming; He, Chunting; Du, Guangsheng; Sun, Xun","year":2022,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 344, 134-146","doi":"10.1016/j.jconrel.2022.02.027","pmid":"35217098","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The new nanovaccine significantly inhibited tumor growth and prolonged survival in mouse models.","whyItMatters":"This research could lead to more effective cancer vaccines by improving immune responses. Enhancing T cell activation is crucial for better tumor elimination.","specificNumbers":"","methodology":"The study involved engineering a dual-epitope peptide vaccine delivered by aluminum nanoparticles and testing its effects on tumor growth in mouse models.","limitations":"The study was conducted in mouse models, and results may not directly translate to humans. Further clinical trials are needed."},{"rthcId":"RPEP-05995","title":"Functional ligands for improving anticancer drug therapy: current status and applications to drug delivery systems.","authors":"Bajracharya, Rajiv; Song, Jae Geun; Patil, Basavaraj Rudragouda; Lee, Sang Hoon; Noh, Hye-Mi; Kim, Da-Hyun; Kim, Gyu-Lin; Seo, Soo-Hwa; Park, Ji-Won; Jeong, Seong Hoon; Lee, Chang Hoon; Han, Hyo-Kyung","year":2022,"journal":"Drug delivery, 29(1), 1959-1970","doi":"10.1080/10717544.2022.2089296","pmid":"35762636","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Functional ligands enhance drug delivery efficiency and target selectivity in cancer therapy.","whyItMatters":"Improving drug delivery systems can significantly reduce side effects and enhance the effectiveness of chemotherapy. This research could lead to better patient outcomes in cancer treatment.","specificNumbers":"","methodology":"The study is a review of existing literature on functional ligands used in drug delivery systems for cancer treatment.","limitations":"As a review, it summarizes existing studies rather than presenting new experimental data."},{"rthcId":"RPEP-05996","title":"Evaluation of PepT1 (SLC15A1) Substrate Characteristics of Therapeutic Cyclic Peptides.","authors":"Bajraktari-Sylejmani, Gzona; von Linde, Teresa; Burhenne, Jürgen; Haefeli, Walter Emil; Sauter, Max; Weiss, Johanna","year":2022,"journal":"Pharmaceutics, 14(8)","doi":"10.3390/pharmaceutics14081610","pmid":"36015235","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Octreotide and pasireotide are nonsubstrate inhibitors of hPepT1.","whyItMatters":"Understanding how these peptides are absorbed can inform drug development and improve therapeutic effectiveness. This research highlights the limitations of using hPepT1 for drug absorption strategies.","specificNumbers":"","methodology":"The study involved creating a cell line that overexpresses the hPepT1 transporter and testing the uptake of cyclic peptides.","limitations":"The study was conducted in vitro, which may not fully represent in vivo conditions in humans."},{"rthcId":"RPEP-05997","title":"Optimized Anchor-Modified Peptides Targeting Mutated RAS Are Promising Candidates for Immunotherapy.","authors":"Baleeiro, Renato B; Dunmall, Louisa S Chard; Liu, Peng; Lu, Shuangshuang; Lone, Yuchun; Lemoine, Nicholas R; Wang, Yaohe","year":2022,"journal":"Frontiers in immunology, 13, 902709","doi":"10.3389/fimmu.2022.902709","pmid":"35720289","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The researchers identified immunogenic peptides from six common codon 12 RAS mutations (G12A, G12C, G12D, G12R, G12S, and G12V) that bind to HLA-A*02:01 and HLA-A*03:01, the two most common HLA types. These peptides elicited strong CD8+ T cell responses.\n\nModifying the anchor residues of these peptides enhanced their binding affinity to HLA-A*02:01, and the resulting T cells responded to both the modified and original peptide forms. Crucially, cytotoxic T cells generated against these peptides specifically lysed tumor cells expressing mutant RAS. In humanized HLA-A2/DR1 mice, vaccination with a long peptide containing an anchor-modified G12V epitope generated CD8+ T cells that recognized both the original peptide and a human cancer cell line harboring the G12V mutation.","whyItMatters":"RAS is the most commonly mutated oncogene in human cancer, but targeting it with conventional drugs has been extremely difficult — earning it the label 'undruggable.' This peptide immunotherapy approach sidesteps the problem entirely by training the patient's own immune system to seek out and destroy RAS-mutant cancer cells. If it works in clinical trials, it could benefit the ~20% of cancer patients whose tumors carry RAS mutations.","specificNumbers":"","methodology":"The team identified candidate peptides from six RAS codon 12 mutations and tested their binding to common HLA molecules. They then modified anchor residues to improve binding affinity. T cell responses were evaluated in vitro using human blood cells and in vivo using transgenic mice expressing human HLA-A2/DR1. Tumor cell killing was assessed using cytotoxicity assays against RAS-mutant cancer cell lines.","limitations":"The in vivo results come from humanized transgenic mice, which approximate but don't fully replicate the human immune system. The study focused on codon 12 mutations and two HLA types, covering a significant but not complete portion of RAS mutations and patient populations. The modified peptides improve T cell activation but the clinical efficacy — whether enough T cells can be generated and sustained to control tumors in patients — remains unproven. No human clinical trial data is available."},{"rthcId":"RPEP-05998","title":"Skin codelivery of contact sensitizers and neurokinin-1 receptor antagonists integrated in microneedle arrays suppresses allergic contact dermatitis.","authors":"Bandyopadhyay, Mohna; Morelli, Adrian E; Balmert, Stephen C; Ward, Nicole L; Erdos, Geza; Sumpter, Tina L; Korkmaz, Emrullah; Kaplan, Daniel H; Oberbarnscheidt, Martin H; Tkacheva, Olga; Shufesky, William J; Falo, Louis D; Larregina, Adriana T","year":2022,"journal":"The Journal of allergy and clinical immunology, 150(1), 114-130","doi":"10.1016/j.jaci.2021.12.794","pmid":"35085664","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Skin codelivery of hapten and NK1R antagonists reduced CD symptoms and inflammation in mice and human skin.","whyItMatters":"This research presents a novel therapeutic strategy for managing allergic contact dermatitis, which currently lacks effective treatments. By targeting specific immune pathways, it may lead to more effective and tailored therapies.","specificNumbers":"","methodology":"The study utilized in vivo mouse models and ex vivo human skin models to assess the effects of NK1R signaling and the immunosuppressive potential of the microneedle arrays.","limitations":"The study was conducted in mouse models, and results may not directly translate to humans. Further research is needed to confirm efficacy in human subjects."},{"rthcId":"RPEP-05999","title":"Inverse age-related changes between hypothalamic NPY and KISS1 gene expression during pubertal initiation in male rhesus monkey.","authors":"Bano, Riffat; Shamas, Shazia; Khan, Saeed Ul H; Shahab, Muhammad","year":2022,"journal":"Reproductive biology, 22(1), 100599","doi":"10.1016/j.repbio.2021.100599","pmid":"35033902","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"KISS1 and KISS1R levels significantly declined in pre-pubertal monkeys compared to infants.","whyItMatters":"Understanding the role of NPY and KISS1 in puberty could lead to new approaches in managing fertility issues in humans.","specificNumbers":"","methodology":"The study used RT-qPCR to analyze gene expression in the mediobasal hypothalamus of male rhesus monkeys at various developmental stages.","limitations":"The study's small sample size may limit the generalizability of the findings."},{"rthcId":"RPEP-06000","title":"Predictors of response to anti-CGRP monoclonal antibodies: a 24-week, multicenter, prospective study on 864 migraine patients.","authors":"Barbanti, Piero; Egeo, Gabriella; Aurilia, Cinzia; Altamura, Claudia; d'Onofrio, Florindo; Finocchi, Cinzia; Albanese, Maria; Aguggia, Marco; Rao, Renata; Zucco, Maurizio; Frediani, Fabio; Filippi, Massimo; Messina, Roberta; Cevoli, Sabina; Carnevale, Antonio; Fiorentini, Giulia; Messina, Stefano; Bono, Francesco; Torelli, Paola; Proietti, Stefania; Bonassi, Stefano; Vernieri, Fabrizio","year":2022,"journal":"The journal of headache and pain, 23(1), 138","doi":"10.1186/s10194-022-01498-6","pmid":"36316648","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In high-frequency episodic migraine, a ≥50% response was linked to unilateral pain and autonomic symptoms (OR: 4.23).","whyItMatters":"Identifying predictors of treatment response can help tailor migraine therapies, potentially improving patient outcomes. This personalized approach could lead to more effective management of migraine.","specificNumbers":"","methodology":"The study involved 864 adult migraine patients treated with anti-CGRP mAbs across 20 centers, using a semi-structured questionnaire to gather data.","limitations":"The study may not account for all variables affecting treatment response and was limited to specific patient populations."},{"rthcId":"RPEP-06001","title":"Stable Gastric Pentadecapeptide BPC 157 May Counteract Myocardial Infarction Induced by Isoprenaline in Rats.","authors":"Barisic, Ivan; Balenovic, Diana; Udovicic, Mario; Bardak, Darija; Strinic, Dean; Vlainić, Josipa; Vranes, Hrvoje; Smoday, Ivan Maria; Krezic, Ivan; Milavic, Marija; Sikiric, Suncana; Uzun, Sandra; Zivanovic Posilovic, Gordana; Strbe, Sanja; Vukoja, Ivan; Lovric, Eva; Lozic, Marin; Sever, Marko; Lovric Bencic, Martina; Boban Blagaic, Alenka; Skrtic, Anita; Seiwerth, Sven; Sikiric, Predrag","year":2022,"journal":"Biomedicines, 10(2)","doi":"10.3390/biomedicines10020265","pmid":"35203478","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BPC-157 at doses of 10 ng/kg and 10 µg/kg (given intraperitoneally either 30 min before or 5 min after isoprenaline) significantly reduced all necrosis markers: CK, CK-MB, LDH, and cardiac troponin T. Treated rats showed no visible infarcted area on gross examination, attenuated histological damage, no ST-T ischemic changes on ECG, and preservation of systolic left ventricular function on echocardiography.\n\nBPC-157 also counteracted the early multi-organ failure seen at 30 min post-isoprenaline (brain, heart, lung, liver, kidney, and GI lesions), reduced thrombosis, and normalized vascular pressures (intracranial, portal, caval hypertension and aortal hypotension) via activation of the azygos vein. The protective effects involved reduced oxidative stress and maintained NO system function through interaction with eNOS and COX2 gene expression.","whyItMatters":"Heart attacks cause irreversible damage within minutes, and current treatments focus on restoring blood flow rather than directly protecting heart tissue. BPC-157's ability to reduce infarct size, preserve cardiac function, and prevent multi-organ complications in this model suggests potential as a cardioprotective agent. The finding that it worked even when given after the heart attack onset is particularly relevant for therapeutic application.","specificNumbers":"","methodology":"Rats received BPC-157 (10 ng/kg or 10 µg/kg IP), L-NAME (NOS blocker, 5 mg/kg IP), and L-arginine (NO precursor, 200 mg/kg IP) alone or in combination, either 30 min before or 5 min after isoprenaline (75 or 150 mg/kg SC). Myocardial infarction (single dose) and reinfarction (doses at 0h and 24h) models were used. Assessment included cardiac biomarkers, gross and histological examination, ECG, echocardiography, oxidative stress parameters, vascular pressure measurements, and gene expression analysis.","limitations":"This is an animal study using a chemical model of myocardial infarction (isoprenaline), which differs from the coronary artery blockage that causes most human heart attacks. No human data exist for BPC-157 in cardiac settings. The study comes from the Sikiric group, which produces the majority of BPC-157 research, limiting independent replication. Specific sample sizes per group and detailed statistical analyses are not provided in the abstract. The isoprenaline model primarily causes subendocardial necrosis rather than transmural infarction."},{"rthcId":"RPEP-06002","title":"Review article: role of glucagon-like peptide-1 receptor agonists in non-alcoholic steatohepatitis, obesity and diabetes-what hepatologists need to know.","authors":"Barritt, A Sidney; Marshman, Emma; Noureddin, Mazen","year":2022,"journal":"Alimentary pharmacology & therapeutics, 55(8), 944-959","doi":"10.1111/apt.16794","pmid":"35266164","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Liraglutide and semaglutide led to histological resolution of NASH in ~40% to 60% of patients.","whyItMatters":"Understanding the role of GLP-1RAs in treating NASH could provide new therapeutic options for patients with limited treatment choices. This research may lead to improved management of obesity and related metabolic disorders.","specificNumbers":"","methodology":"The study involved a review of existing literature and meta-analyses on GLP-1RAs and their effects on NASH.","limitations":"The review primarily summarizes existing studies, and the long-term effects and safety of GLP-1RAs in NASH require further investigation."},{"rthcId":"RPEP-06003","title":"Alterations in Immune-Related Defensin Alpha 4 (DEFA4) Gene Expression in Health and Disease.","authors":"Basingab, Fatemah; Alsaiary, Abeer; Almontashri, Shahad; Alrofaidi, Aisha; Alharbi, Mona; Azhari, Sheren; Algothmi, Khloud; Alhazmi, Safiah","year":2022,"journal":"International journal of inflammation, 2022, 9099136","doi":"10.1155/2022/9099136","pmid":"35668817","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"DEFA4 is up-regulated in aggressive cancer forms and shows antiviral activity against HIV-1.","whyItMatters":"Understanding DEFA4's role could lead to new treatments for infections and cancers. Its potential against antibiotic-resistant bacteria is particularly significant.","specificNumbers":"","methodology":"The study is a review of existing literature on DEFA4 gene expression from 1988 to 2022.","limitations":"As a review, it does not present new experimental data and relies on existing studies, which may vary in quality."},{"rthcId":"RPEP-06004","title":"The oncogenic fusion protein DNAJB1-PRKACA can be specifically targeted by peptide-based immunotherapy in fibrolamellar hepatocellular carcinoma.","authors":"Bauer, Jens; Köhler, Natalie; Maringer, Yacine; Bucher, Philip; Bilich, Tatjana; Zwick, Melissa; Dicks, Severin; Nelde, Annika; Dubbelaar, Marissa; Scheid, Jonas; Wacker, Marcel; Heitmann, Jonas S; Schroeder, Sarah; Rieth, Jonas; Denk, Monika; Richter, Marion; Klein, Reinhild; Bonzheim, Irina; Luibrand, Julia; Holzer, Ursula; Ebinger, Martin; Brecht, Ines B; Bitzer, Michael; Boerries, Melanie; Feucht, Judith; Salih, Helmut R; Rammensee, Hans-Georg; Hailfinger, Stephan; Walz, Juliane S","year":2022,"journal":"Nature communications, 13(1), 6401","doi":"10.1038/s41467-022-33746-3","pmid":"36302754","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"DNAJB1-PRKACA fusion-derived peptides were confirmed as genuine HLA-presented neoantigens on tumor cells by mass spectrometry-based immunopeptidome analysis. These peptides induced both cytotoxic CD8+ T cells and T-helper 1 CD4+ T cells in preclinical testing. Single-cell RNA sequencing identified multiple T cell receptors specific for the fusion neoepitopes.\n\nIn a single-patient clinical application, vaccination with DNAJB1-PRKACA-derived peptides (combined with ongoing PARP inhibitor therapy) induced multifunctional CD4+ T cells with activated Th1 phenotype and high T cell receptor clonality. The vaccine-induced immune responses persisted over time and were accompanied by durable relapse-free survival of more than 21 months — in striking contrast to the patient's previous pattern of recurrent short-interval relapses under various treatments.","whyItMatters":"Fibrolamellar hepatocellular carcinoma has no approved targeted therapies and is often fatal. This study demonstrates that the cancer's driving mutation — present in virtually all cases — can be specifically targeted by peptide immunotherapy. Because nearly every patient carries the same fusion, this approach could become a standardized treatment rather than requiring individualized neoantigen identification, making it more practical than most personalized cancer vaccines.","specificNumbers":"","methodology":"Multi-stage study: (1) Identification of HLA class I and II neoantigen peptides from the DNAJB1-PRKACA fusion using mass spectrometry immunopeptidomics, (2) in vitro characterization of T cell responses to these peptides, (3) single-cell RNA sequencing of fusion-specific T cells to identify T cell receptors, and (4) clinical vaccination of one fibrolamellar HCC patient with the identified peptides alongside continued PARP inhibitor therapy, with longitudinal immune monitoring.","limitations":"This is a single-patient clinical observation — the gold standard of evidence (randomized controlled trial) has not been met. The patient also received concurrent PARP inhibitor therapy, making it impossible to attribute the clinical benefit solely to the vaccine. The durability beyond 21 months and response in other patients are unknown. Mass spectrometry-based neoantigen identification requires specialized infrastructure not available at most centers."},{"rthcId":"RPEP-06005","title":"CD8 T cell function and cross-reactivity explored by stepwise increased peptide-HLA versus TCR affinity.","authors":"Baumgaertner, Petra; Schmidt, Julien; Costa-Nunes, Carla-Marisa; Bordry, Natacha; Guillaume, Philippe; Luescher, Immanuel; Speiser, Daniel E; Rufer, Nathalie; Hebeisen, Michael","year":2022,"journal":"Frontiers in immunology, 13, 973986","doi":"10.3389/fimmu.2022.973986","pmid":"36032094","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Vaccines containing the native (unmodified) Melan-A/MART-1 tumor peptide generated CD8 T cells with better functionality and superior cross-reactivity against potential low-affinity escape variants, compared to T cells induced by vaccines with an HLA affinity-optimized peptide.\n\nUsing affinity-optimized NY-ESO-1-specific T cell receptors, the researchers found that peptide:HLA affinity and TCR-peptide:HLA affinity both have profound and distinct effects on T cell responses, with additive contributions and no hierarchical dominance of one parameter over the other. T cells from tumor-infiltrated lymph nodes showed heterogeneous, clonotype-dependent functional profiles.","whyItMatters":"Cancer peptide vaccines are a major area of immunotherapy research, and optimizing which peptide to include is critical for their success. This study challenges the assumption that stronger-binding peptides make better vaccines. Instead, it shows that natural peptides can produce more versatile T cells capable of recognizing tumor cells even when they mutate to escape immune detection. This has direct implications for how cancer vaccines are designed.","specificNumbers":"","methodology":"The researchers created two panels of human tumor peptide variants with different HLA binding affinities. They developed a novel 'blue peptide assay' — an upgraded cell-based method to precisely measure peptide:HLA affinity. Using these tools, they characterized CD8 T cell clonotypes from cancer patients who had been vaccinated with either native or optimized Melan-A/MART-1 peptides, plus T cells isolated from tumor-infiltrated lymph nodes. They also used a collection of affinity-optimized NY-ESO-1-specific TCRs to dissect the individual and combined effects of the two affinity parameters.","limitations":"The study focuses on two specific tumor antigens (Melan-A/MART-1 and NY-ESO-1) in the context of melanoma, so findings may not generalize to all tumor types or antigens. The number of patient-derived T cell clonotypes analyzed is not specified in the abstract. The blue peptide assay is novel and may require broader validation. The study examines T cell function in vitro, which may not fully predict in vivo anti-tumor activity."},{"rthcId":"RPEP-06006","title":"Inhibition of MRGPRX2 but not FcεRI or MrgprB2-mediated mast cell degranulation by a small molecule inverse receptor agonist.","authors":"Bawazir, Maram; Amponnawarat, Aetas; Hui, Yvonne; Oskeritzian, Carole A; Ali, Hydar","year":2022,"journal":"Frontiers in immunology, 13, 1033794","doi":"10.3389/fimmu.2022.1033794","pmid":"36275683","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"C9 selectively inhibited MRGPRX2-mediated mast cell degranulation with an IC50 of approximately 300 nM. Key specifics:\n\n• C9 blocked degranulation in response to substance P, PAMP-12 (a pro-adrenomedullin peptide), and rocuronium in cells expressing MRGPRX2\n• C9 did NOT inhibit mast cell activation through FcεRI (IgE receptor) or the anaphylatoxin C3a — demonstrating high selectivity for MRGPRX2\n• C9 also blocked β-arrestin recruitment and receptor internalization, inhibiting both major signaling arms of MRGPRX2\n• An inactive analog (C7) had no effect, confirming the specificity of C9's action\n• A naturally occurring MRGPRX2 variant (V282M) that shows constitutive β-arrestin activity was also significantly inhibited by C9\n• C9 did not block the mouse ortholog MrgprB2, indicating species specificity","whyItMatters":"Many drug hypersensitivity reactions and chronic skin conditions like urticaria, itch, and neurogenic inflammation are driven by mast cell activation through MRGPRX2 — not through traditional IgE allergies. Current treatments like antihistamines and steroids are broad and often inadequate. A selective MRGPRX2 blocker like C9 could offer a targeted approach to these conditions while leaving the immune system's IgE-based defenses intact.","specificNumbers":"","methodology":"Researchers tested C9 in multiple cell systems: RBL-2H3 cells engineered to express human MRGPRX2, LAD2 mast cell line, human skin-derived mast cells, and mouse peritoneal mast cells. They measured degranulation using β-hexosaminidase release, CD63 and CD107a surface expression. They also assessed β-arrestin recruitment and receptor internalization. The inactive analog C7 served as a negative control, and various agonists (substance P, PAMP-12, rocuronium, C3a, IgE crosslinking) were used to test selectivity.","limitations":"All experiments were conducted in cell lines, engineered cells, or isolated mouse mast cells — no in vivo animal studies or human trials were performed. C9 did not block the mouse ortholog MrgprB2, which limits the ability to test it in mouse disease models. The long-term effects, bioavailability, and safety profile of C9 are unknown. Translation from cell culture to clinical therapy remains a significant gap."},{"rthcId":"RPEP-06007","title":"Liver-Expressed Antimicrobial Peptide 2 antagonizes the insulinostatic effect of ghrelin in rat isolated pancreatic islets.","authors":"Bayle, Morgane; Péraldi-Roux, Sylvie; Gautheron, Guillaume; Cros, Gérard; Oiry, Catherine; Neasta, Jérémie","year":2022,"journal":"Fundamental & clinical pharmacology, 36(2), 375-377","doi":"10.1111/fcp.12722","pmid":"34449915","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"LEAP2 blocked the insulinostatic action of ghrelin without modulating glucose-stimulated insulin secretion.","whyItMatters":"Understanding how LEAP2 interacts with ghrelin could provide insights into insulin regulation and potential treatments for metabolic disorders.","specificNumbers":"","methodology":"Rat pancreatic islets were isolated and exposed to glucose with or without LEAP2 and ghrelin to measure insulin secretion.","limitations":"The study was conducted in isolated rat pancreatic islets, which may not fully represent human physiology."},{"rthcId":"RPEP-06008","title":"The Role of Glp-1 Receptor Agonists in Insulin Resistance with Concomitant Obesity Treatment in Polycystic Ovary Syndrome.","authors":"Bednarz, Krzysztof; Kowalczyk, Karolina; Cwynar, Marlena; Czapla, Dominika; Czarkowski, Wiktor; Kmita, Dominika; Nowak, Artur; Madej, Paweł","year":2022,"journal":"International journal of molecular sciences, 23(8)","doi":"10.3390/ijms23084334","pmid":"35457152","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 receptor agonists improve insulin resistance and reduce obesity-related factors in PCOS patients.","whyItMatters":"Understanding the role of GLP-1 receptor agonists could lead to better management strategies for women with PCOS, a condition that affects many and can lead to serious health issues.","specificNumbers":"","methodology":"The study reviews existing literature on the effects of GLP-1 receptor agonists in women with PCOS and obesity.","limitations":"The study is based on literature review and does not provide new experimental data."},{"rthcId":"RPEP-06009","title":"The anti-inflammatory and immunological properties of GLP-1 Receptor Agonists.","authors":"Bendotti, Giulia; Montefusco, Laura; Lunati, Maria Elena; Usuelli, Vera; Pastore, Ida; Lazzaroni, Elisa; Assi, Emma; Seelam, Andy Joe; El Essawy, Basset; Jang, Jun; Loretelli, Cristian; D'Addio, Francesca; Berra, Cesare; Ben Nasr, Moufida; Zuccotti, GianVincenzo; Fiorina, Paolo","year":2022,"journal":"Pharmacological research, 182, 106320","doi":"10.1016/j.phrs.2022.106320","pmid":"35738455","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 receptor agonists have demonstrated anti-inflammatory effects across different tissues.","whyItMatters":"Understanding the anti-inflammatory effects of GLP-1RAs could lead to new treatments for inflammatory diseases. This research expands the therapeutic potential of these drugs beyond diabetes and obesity.","specificNumbers":"","methodology":"The study is a review of existing literature on the effects of GLP-1 receptor agonists, focusing on their anti-inflammatory and immunological properties.","limitations":"The study is a review and does not include original experimental data; results may vary in clinical settings."},{"rthcId":"RPEP-06010","title":"Considerations in the developability of peptides for oral administration when formulated together with transient permeation enhancers.","authors":"Berg, Staffan; Edlund, Helena; R F Goundry, William; A S Bergström, Christel; Davies, Nigel M","year":2022,"journal":"International journal of pharmaceutics, 628, 122238","doi":"10.1016/j.ijpharm.2022.122238","pmid":"36174850","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Oral bioavailability of peptides remains low, often in single digits, with high variability.","whyItMatters":"Improving oral bioavailability of peptides could enhance their therapeutic use, making them more accessible and effective for patients.","specificNumbers":"","methodology":"The paper is a review that discusses various properties of peptides and their interactions with permeation enhancers.","limitations":"As a review, it does not present original experimental data and may not cover all recent advancements in the field."},{"rthcId":"RPEP-06011","title":"Human β-Defensin 2 (HBD-2) Displays Oncolytic Activity but Does Not Affect Tumour Cell Migration.","authors":"Bindra, Guneet K; Williams, Scott A; Lay, Fung T; Baxter, Amy A; Poon, Ivan K H; Hulett, Mark D; Phan, Thanh Kha","year":2022,"journal":"Biomolecules, 12(2)","doi":"10.3390/biom12020264","pmid":"35204765","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"HBD-2 induced acute lytic cell death in tumor cells but did not affect their migration.","whyItMatters":"Understanding how HBD-2 works could lead to new cancer therapies that leverage its oncolytic properties. However, the lack of effect on migration raises questions about its overall therapeutic potential.","specificNumbers":"","methodology":"The study utilized various cell biological assays and confocal microscopy to assess the effects of HBD-2 on tumor cells.","limitations":"The study primarily focuses on in vitro effects, which may not fully translate to in vivo conditions or human patients."},{"rthcId":"RPEP-06012","title":"Endogenous opiates and behavior: 2020.","authors":"Bodnar, Richard J","year":2022,"journal":"Peptides, 151, 170752","doi":"10.1016/j.peptides.2022.170752","pmid":"35114317","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review encompasses findings from 18 specific topics related to endogenous opioids.","whyItMatters":"Understanding the role of endogenous opiates can help in developing better pain management strategies and addressing mental health issues. This knowledge is crucial for both clinical applications and further research.","specificNumbers":"","methodology":"This is an anthological review summarizing multiple studies on endogenous opioids published in 2020.","limitations":"As a review, it synthesizes existing studies but does not present new experimental data."},{"rthcId":"RPEP-06013","title":"Effects on weight loss and glycemic control with SAR441255, a potent unimolecular peptide GLP-1/GIP/GCG receptor triagonist.","authors":"Bossart, Martin; Wagner, Michael; Elvert, Ralf; Evers, Andreas; Hübschle, Thomas; Kloeckener, Tim; Lorenz, Katrin; Moessinger, Christine; Eriksson, Olof; Velikyan, Irina; Pierrou, Stefan; Johansson, Lars; Dietert, Gabriele; Dietz-Baum, Yasmin; Kissner, Thomas; Nowotny, Irene; Einig, Christine; Jan, Christelle; Rharbaoui, Faiza; Gassenhuber, Johann; Prochnow, Hans-Peter; Agueusop, Inoncent; Porksen, Niels; Smith, William B; Nitsche, Almut; Konkar, Anish","year":2022,"journal":"Cell metabolism, 34(1), 59-74.e10","doi":"10.1016/j.cmet.2021.12.005","pmid":"34932984","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"SAR441255 improved glycemic control and weight loss compared to dual receptor agonists.","whyItMatters":"This research highlights a potential new treatment for obesity and diabetes by leveraging multiple hormonal pathways. It may lead to more effective therapies with fewer side effects.","specificNumbers":"","methodology":"The study involved preclinical testing in rodent models and a mixed-meal tolerance test in healthy human subjects.","limitations":"The study primarily involved animal models and a small group of healthy subjects, which may limit the generalizability of the findings."},{"rthcId":"RPEP-06014","title":"Cell-Penetrating Peptides (CPPs) as Therapeutic and Diagnostic Agents for Cancer.","authors":"Bottens, Ryan A; Yamada, Tohru","year":2022,"journal":"Cancers, 14(22)","doi":"10.3390/cancers14225546","pmid":"36428639","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CPPs can improve drug delivery and targeting in cancer treatment, showing significant potential in clinical trials.","whyItMatters":"CPPs could revolutionize cancer treatment by enhancing drug delivery and reducing side effects, making therapies more effective.","specificNumbers":"","methodology":"The study is a review based on systematic searches in multiple scientific databases.","limitations":"As a review, it does not present original experimental data and relies on existing studies."},{"rthcId":"RPEP-06015","title":"The Importance of Experimental Investigation of the CNS Oxytocin System.","authors":"Boulton, Kelsie A; Guastella, Adam J","year":2022,"journal":"Methods in molecular biology (Clifton, N.J.), 2384, 53-65","doi":"10.1007/978-1-0716-1759-5_4","pmid":"34550568","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review synthesizes evidence showing that the oxytocin system influences social behavior through multiple pathways — direct intranasal administration, genetic variation in oxytocin-related genes, and epigenetic modifications. The contrasting social phenotypes of autism spectrum disorder (social difficulties) and Williams syndrome (excessive sociability) provide a natural experiment for understanding the oxytocinergic system.\n\nThe authors conclude that inconsistencies in oxytocin research stem largely from methodological issues: problems with measuring central oxytocin levels, variable intranasal administration protocols, and failure to account for individual differences in the oxytocin system that determine treatment response.","whyItMatters":"Oxytocin has been one of the most hyped peptides in neuroscience and psychiatry, but clinical results have been inconsistent. This review provides a clear-eyed assessment of why — identifying specific methodological gaps that, if addressed, could unlock oxytocin's therapeutic potential for conditions like autism where effective social behavior treatments are desperately needed.","specificNumbers":"","methodology":"Narrative review chapter synthesizing published research on the oxytocin system, including intranasal oxytocin clinical studies, genetic and epigenetic association studies, and neurodevelopmental disorder research. No original experimental data were generated.","limitations":"As a review chapter, it synthesizes existing literature but does not generate new data. The coverage may not include the most recent studies published after the review was written. The discussion is primarily limited to autism and Williams syndrome and does not cover all conditions where oxytocin has been investigated."},{"rthcId":"RPEP-06016","title":"Ionic signalling mechanisms involved in neurokinin-3 receptor-mediated augmentation of fear-potentiated startle response in the basolateral amygdala.","authors":"Boyle, Cody A; Hu, Binqi; Quaintance, Kati L; Mastrud, Morgan R; Lei, Saobo","year":2022,"journal":"The Journal of physiology, 600(19), 4325-4345","doi":"10.1113/JP283433","pmid":"36030507","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Activation of NK3 receptors in the BLA increased fear-potentiated startle response.","whyItMatters":"Understanding how NK3 receptors influence fear responses could lead to new insights into anxiety disorders and potential therapeutic targets.","specificNumbers":"","methodology":"The study used selective agonists and antagonists, along with channel blockers and knockout mice, to explore the effects of NK3 receptor activation on neuron excitability and fear responses.","limitations":"The study was conducted in rats, and results may not directly translate to humans. Additionally, the long-term effects of NK3R activation were not assessed."},{"rthcId":"RPEP-06017","title":"A Radiotracer for Molecular Imaging and Therapy of Gastrin-Releasing Peptide Receptor-Positive Prostate Cancer.","authors":"Bratanovic, Ivica J; Zhang, Chengcheng; Zhang, Zhengxing; Kuo, Hsiou-Ting; Colpo, Nadine; Zeisler, Jutta; Merkens, Helen; Uribe, Carlos; Lin, Kuo-Shyan; Bénard, François","year":2022,"journal":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 63(3), 424-430","doi":"10.2967/jnumed.120.257758","pmid":"34301778","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06018","title":"Do gluten peptides stimulate weight gain in humans?","authors":"Brouns, Fred; Shewry, Peter R","year":2022,"journal":"Nutrition bulletin, 47(2), 186-198","doi":"10.1111/nbu.12558","pmid":"35915782","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"No evidence supports that gluten peptides drive appetite or weight gain in humans.","whyItMatters":"Understanding the relationship between gluten and weight gain can help clarify dietary recommendations. This review challenges common beliefs about gluten's impact on obesity.","specificNumbers":"","methodology":"This is a narrative review discussing existing literature on gluten peptides and weight gain.","limitations":"The study is a review and does not provide new experimental data; it relies on existing literature."},{"rthcId":"RPEP-06019","title":"Identification of a PCSK9-LDLR disruptor peptide with in vivo function.","authors":"Brousseau, Margaret E; Clairmont, Kevin B; Spraggon, Glen; Flyer, Alec N; Golosov, Andrei A; Grosche, Philipp; Amin, Jakal; Andre, Jerome; Burdick, Debra; Caplan, Shari; Chen, Guanjing; Chopra, Raj; Ames, Lisa; Dubiel, Diana; Fan, Li; Gattlen, Raphael; Kelly-Sullivan, Dawn; Koch, Alexander W; Lewis, Ian; Li, Jingzhou; Liu, Eugene; Lubicka, Danuta; Marzinzik, Andreas; Nakajima, Katsumasa; Nettleton, David; Ottl, Johannes; Pan, Meihui; Patel, Tajesh; Perry, Lauren; Pickett, Stephanie; Poirier, Jennifer; Reid, Patrick C; Pelle, Xavier; Seepersaud, Mohindra; Subramanian, Vanitha; Vera, Victoria; Xu, Mei; Yang, Lihua; Yang, Qing; Yu, Jinghua; Zhu, Guoming; Monovich, Lauren G","year":2022,"journal":"Cell chemical biology, 29(2), 249-258.e5","doi":"10.1016/j.chembiol.2021.08.012","pmid":"34547225","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The peptide 13PCSK9i reduces plasma cholesterol levels and increases hepatic LDLR density in a dose-dependent manner in mice.","whyItMatters":"This discovery could lead to new treatments for lowering cholesterol and reducing cardiovascular disease risk. By targeting the PCSK9-LDLR interaction, it offers a novel approach to managing cholesterol levels.","specificNumbers":"","methodology":"The researchers conducted an affinity-based screen of 1013 in vitro-translated macrocyclic peptides to identify high-affinity PCSK9 ligands.","limitations":"The study was conducted in mice, and results may not directly translate to humans. Further research is needed to evaluate safety and efficacy in human subjects."},{"rthcId":"RPEP-06020","title":"Effects of Substance P and Neurokinin A on the Contractile Activity of Inflamed Porcine Uterus.","authors":"Brzozowska, Marta; Romaniewicz, Marta; Całka, Jarosław; Jana, Barbara","year":2022,"journal":"International journal of molecular sciences, 23(21)","doi":"10.3390/ijms232113184","pmid":"36361972","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Substance P reduced contraction amplitude and frequency, while neurokinin A increased frequency but reduced amplitude in inflamed uterine tissue.","whyItMatters":"Understanding how these substances affect uterine contractions could lead to new treatments for inflammatory conditions in the uterus. This research may have implications for improving reproductive health in livestock and potentially in humans.","specificNumbers":"","methodology":"The study involved inducing inflammation in pig uteri with E. coli and measuring the effects of substance P and neurokinin A on uterine contractility.","limitations":"The study was conducted in pigs, so results may not directly translate to humans. Additionally, the sample size and specific conditions of the experiment may limit generalizability."},{"rthcId":"RPEP-06021","title":"Evaluating performance of existing computational models in predicting CD8+ T cell pathogenic epitopes and cancer neoantigens.","authors":"Buckley, Paul R; Lee, Chloe H; Ma, Ruichong; Woodhouse, Isaac; Woo, Jeongmin; Tsvetkov, Vasily O; Shcherbinin, Dmitrii S; Antanaviciute, Agne; Shughay, Mikhail; Rei, Margarida; Simmons, Alison; Koohy, Hashem","year":2022,"journal":"Briefings in bioinformatics, 23(3)","doi":"10.1093/bib/bbac141","pmid":"35471658","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"None of the models significantly outperformed random predictions for immunogenic peptides.","whyItMatters":"Improving predictions of T cell targets is crucial for developing effective vaccines and cancer therapies. Understanding model limitations can guide future research and model development.","specificNumbers":"","methodology":"The study systematically evaluated several publicly available models for predicting CD8+ T cell targets in the context of pathogens and cancers.","limitations":"The study primarily focused on existing models without developing new predictive tools, and results may not directly translate to clinical settings."},{"rthcId":"RPEP-06022","title":"Human Sensory Neuron-like Cells and Glycated Collagen Matrix as a Model for the Screening of Analgesic Compounds.","authors":"Bufalo, Michelle Cristiane; Almeida, Maíra Estanislau Soares de; Jensen, José Ricardo; DeOcesano-Pereira, Carlos; Lichtenstein, Flavio; Picolo, Gisele; Chudzinski-Tavassi, Ana Marisa; Sampaio, Sandra Coccuzzo; Cury, Yara; Zambelli, Vanessa Olzon","year":2022,"journal":"Cells, 11(2)","doi":"10.3390/cells11020247","pmid":"35053363","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The model showed that ECM-GC increased c-Fos expression and substance P release, while morphine decreased substance P release.","whyItMatters":"This research provides a new tool for screening pain relief medications, which is crucial for developing effective treatments for pain-related conditions.","specificNumbers":"","methodology":"The study characterized a model using human sensory-like neurons differentiated from SH-SY5Y cell lines, exposed to a glycated collagen matrix.","limitations":"The study primarily uses a cell line model, which may not fully replicate human physiological responses."},{"rthcId":"RPEP-06023","title":"AMPLIFY-NEOVAC: a randomized, 3-arm multicenter phase I trial to assess safety, tolerability and immunogenicity of IDH1-vac combined with an immune checkpoint inhibitor targeting programmed death-ligand 1 in isocitrate dehydrogenase 1 mutant gliomas.","authors":"Bunse, Lukas; Rupp, Anne-Kathleen; Poschke, Isabel; Bunse, Theresa; Lindner, Katharina; Wick, Antje; Blobner, Jens; Misch, Martin; Tabatabai, Ghazaleh; Glas, Martin; Schnell, Oliver; Gempt, Jens; Denk, Monika; Reifenberger, Guido; Bendszus, Martin; Wuchter, Patrick; Steinbach, Joachim P; Wick, Wolfgang; Platten, Michael","year":2022,"journal":"Neurological research and practice, 4(1), 20","doi":"10.1186/s42466-022-00184-x","pmid":"35599302","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The trial will assess safety and immune response in 48 patients across three treatment arms.","whyItMatters":"This research could lead to improved treatment options for patients with specific brain tumors, potentially enhancing immune responses against cancer. Understanding the safety and effectiveness of this combination therapy could shape future cancer treatment strategies.","specificNumbers":"","methodology":"A randomized, multicenter phase I trial with three arms comparing IDH1-vac alone, IDH1-vac plus AVE, and AVE alone.","limitations":"As a phase I trial, the sample size is small, and results may not be generalizable to all patients with IDH1 mutations."},{"rthcId":"RPEP-06024","title":"Discovery of a Cyclic Cell-Penetrating Peptide with Improved Endosomal Escape and Cytosolic Delivery Efficiency.","authors":"Buyanova, Marina; Sahni, Ashweta; Yang, Rui; Sarkar, Amar; Salim, Heba; Pei, Dehua","year":2022,"journal":"Molecular pharmaceutics, 19(5), 1378-1388","doi":"10.1021/acs.molpharmaceut.1c00924","pmid":"35405068","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CPP12-2 shows up to 3.8-fold higher cytosolic entry efficiency than CPP12.","whyItMatters":"This research could lead to more effective drug delivery systems, particularly for therapies requiring low doses. Improved cellular uptake can enhance the efficacy of treatments.","specificNumbers":"","methodology":"The study involved synthesizing CPP12 analogs and testing their ability to enter cells under various conditions.","limitations":"The study primarily focused on in vitro and in vivo models, which may not fully represent human responses."},{"rthcId":"RPEP-06025","title":"Targeting intracellular protein-protein interactions with macrocyclic peptides.","authors":"Buyanova, Marina; Pei, Dehua","year":2022,"journal":"Trends in pharmacological sciences, 43(3), 234-248","doi":"10.1016/j.tips.2021.11.008","pmid":"34911657","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Recent advances have produced cell-permeable macrocyclic peptides that effectively modulate intracellular PPIs.","whyItMatters":"Understanding how to effectively deliver these peptides into cells could revolutionize drug development for diseases where PPIs play a critical role. This could lead to new treatments for various conditions, including cancer and neurodegenerative diseases.","specificNumbers":"","methodology":"The review synthesizes findings from various studies on the design and efficacy of macrocyclic peptides in targeting intracellular proteins.","limitations":"The review primarily discusses theoretical advancements and lacks experimental data on the clinical efficacy of these peptides."},{"rthcId":"RPEP-06026","title":"The rice bran peptide KF-8 extends the lifespan and improves the healthspan of Caenorhabditis elegans via skn-1 and daf-16.","authors":"Cai, Jie; Chen, Zhongxu; Wu, Yixin; Chen, Yajuan; Wang, Jianqiang; Lin, Qinlu; Liang, Ying","year":2022,"journal":"Food & function, 13(5), 2427-2440","doi":"10.1039/d1fo03718h","pmid":"35170608","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"KF-8 increased lifespan and improved healthspan in C. elegans, with effects lost in skn-1 and daf-16 mutants.","whyItMatters":"Understanding how KF-8 influences aging in worms could provide insights into potential anti-aging strategies in other organisms, including humans.","specificNumbers":"","methodology":"The study involved treating Caenorhabditis elegans with KF-8 and assessing various health and lifespan metrics.","limitations":"The study was conducted in C. elegans, which may not fully represent human biology."},{"rthcId":"RPEP-06027","title":"Synthesis of potent antagonists of receptors for growth hormone-releasing hormone with antitumor and anti-inflammatory activity.","authors":"Cai, Renzhi; Zhang, Xianyang; Wang, Haibo; Cui, Tengjiao; Halmos, Gabor; Sha, Wei; He, Jinlin; Popovics, Petra; Vidaurre, Irving; Zhang, Chongxu; Mirsaeidi, Mehdi; Schally, Andrew V","year":2022,"journal":"Peptides, 150, 170716","doi":"10.1016/j.peptides.2021.170716","pmid":"34952135","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Five of nineteen AVR analogs showed 2-4 fold better binding affinities than MIA-602.","whyItMatters":"These findings highlight the potential of AVR GHRH antagonists as new therapeutic options for cancer treatment and inflammation management. Improved binding affinities and efficacy could lead to more effective clinical applications.","specificNumbers":"","methodology":"The study involved synthesizing AVR analogs and evaluating their effects on cancer cell proliferation in vitro and tumor growth in vivo using nude mice models.","limitations":"The study primarily used in vitro and animal models, which may not fully represent human responses. Further clinical trials are needed to confirm efficacy and safety."},{"rthcId":"RPEP-06028","title":"Acellular dermal matrix decorated with collagen-affinity peptide accelerate diabetic wound healing through sustained releasing Histatin-1 mediated promotion of angiogenesis.","authors":"Cao, Yanpeng; Shi, Xin; Zhao, Xin; Chen, Bei; Li, Xiying; Li, Yabei; Chen, Yaowu; Chen, Can; Lu, Hongbin; Liu, Jun","year":2022,"journal":"International journal of pharmaceutics, 624, 122017","doi":"10.1016/j.ijpharm.2022.122017","pmid":"35839983","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"C-Hst1/ADM significantly promoted angiogenesis and reduced scar widths in diabetic wounds.","whyItMatters":"Diabetic wounds are a major health issue, and improving their healing can reduce complications and healthcare costs. This new method could lead to better treatment options for patients.","specificNumbers":"","methodology":"The study involved creating a collagen-binding peptide and an acellular dermal matrix for sustained release, followed by in vitro and in vivo testing.","limitations":"The study primarily focused on in vitro and animal models, which may not fully translate to human patients."},{"rthcId":"RPEP-06029","title":"Legume Proteins and Peptides as Compounds in Nutraceuticals: A Structural Basis for Dietary Health Effects.","authors":"Carbonaro, Marina; Nucara, Alessandro","year":2022,"journal":"Nutrients, 14(6)","doi":"10.3390/nu14061188","pmid":"35334845","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Legume proteins and peptides exhibit properties such as anticarcinogenic, hypocholesterolemic, and immunostimulant effects.","whyItMatters":"This research underscores the importance of legumes in diets for their health-promoting properties, which could influence dietary recommendations and food security.","specificNumbers":"","methodology":"The study is a review of existing literature on legume proteins and peptides, focusing on their structural features and health effects.","limitations":"As a review, it synthesizes existing research but does not present new experimental data."},{"rthcId":"RPEP-06030","title":"LGD-4033 and MK-677 use impacts body composition, circulating biomarkers, and skeletal muscle androgenic hormone and receptor content: A case report.","authors":"Cardaci, Thomas D; Machek, Steven B; Wilburn, Dylan T; Heileson, Jeffery L; Harris, Dillon R; Cintineo, Harry P; Willoughby, Darryn S","year":2022,"journal":"Experimental physiology, 107(12), 1467-1476","doi":"10.1113/EP090741","pmid":"36303408","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Body mass increased by 6.0%, while total testosterone decreased by 62.3%.","whyItMatters":"Understanding the effects of these compounds is crucial as they are increasingly used among recreational athletes. The negative impacts on health markers highlight the risks involved.","specificNumbers":"","methodology":"A 25-year-old male took LGD-4033 (10 mg) and MK-677 (15 mg) daily for 5 weeks, with assessments of body composition and biomarkers before, during, and after the cycle.","limitations":"The study is based on a single case, limiting the generalizability of the findings."},{"rthcId":"RPEP-06031","title":"Antimicrobial peptide production in response to gut microbiota imbalance.","authors":"Cardoso, Marlon H; Meneguetti, Beatriz T; Oliveira-Júnior, Nelson G; Macedo, Maria L R; Franco, Octávio L","year":2022,"journal":"Peptides, 157, 170865","doi":"10.1016/j.peptides.2022.170865","pmid":"36038014","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06032","title":"An update on cell-penetrating peptides with intracellular organelle targeting.","authors":"Cerrato, Carmine Pasquale; Langel, Ülo","year":2022,"journal":"Expert opinion on drug delivery, 19(2), 133-146","doi":"10.1080/17425247.2022.2034784","pmid":"35086398","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Cell-penetrating peptides conjugated with organelle-targeting sequences represent an advancing strategy for intracellular drug delivery. The review summarizes how CPPs can be engineered to deliver cargo to specific subcellular compartments including mitochondria, nuclei, endoplasmic reticulum, and lysosomes. This organelle-level targeting moves drug delivery beyond tissue-level or cell-level precision, improving therapeutic efficacy while reducing off-target toxicity and potentially overcoming drug resistance mechanisms.","whyItMatters":"Many drugs fail not because they can't reach the right cell, but because they can't reach the right compartment within the cell. For example, some cancer drugs need to reach the nucleus to damage DNA, while others target mitochondria to trigger cell death. CPPs that can deliver drugs directly to these organelles could dramatically improve treatment outcomes for cancer, neurological diseases, and metabolic disorders while reducing the doses needed and minimizing side effects.","specificNumbers":"","methodology":"This is a narrative review article that summarizes published literature on cell-penetrating peptides and their intracellular organelle-targeting capabilities. The authors reviewed current targeting strategies, CPP/cargo complex designs, and pharmacological/therapeutic applications reported in the field through early 2022.","limitations":"As a review article, this paper does not present new experimental data. The field of CPP-mediated organelle targeting is still largely preclinical, with limited clinical validation. Many of the targeting strategies described work well in cell culture but face challenges with in vivo delivery, including stability, immunogenicity, and biodistribution. The review may also reflect the publication bias toward positive results in the CPP literature."},{"rthcId":"RPEP-06033","title":"Mitochondrial Targeting Probes, Drug Conjugates, and Gene Therapeutics.","authors":"Cerrato, Carmine Pasquale; Kivijärvi, Tove; Langel, Ülo","year":2022,"journal":"Methods in molecular biology (Clifton, N.J.), 2383, 429-446","doi":"10.1007/978-1-0716-1752-6_27","pmid":"34766305","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Recent advances in mitochondrial-targeting techniques show promise for therapy.","whyItMatters":"Targeting mitochondria could lead to breakthroughs in treating serious diseases. Improved delivery methods may enhance the effectiveness of therapies.","specificNumbers":"","methodology":"The study reviews methods for delivering oligonucleotides to mitochondria using cell-penetrating peptides.","limitations":"The study is primarily a review and does not present original experimental data."},{"rthcId":"RPEP-06034","title":"Synthetic Antibiotic Derived from Sequences Encrypted in a Protein from Human Plasma.","authors":"Cesaro, Angela; Torres, Marcelo D T; Gaglione, Rosa; Dell'Olmo, Eliana; Di Girolamo, Rocco; Bosso, Andrea; Pizzo, Elio; Haagsman, Henk P; Veldhuizen, Edwin J A; de la Fuente-Nunez, Cesar; Arciello, Angela","year":2022,"journal":"ACS nano, 16(2), 1880-1895","doi":"10.1021/acsnano.1c04496","pmid":"35112568","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The peptides showed potent antimicrobial activity against drug-resistant bacteria and enhanced conventional antibiotics' effectiveness.","whyItMatters":"With rising antibiotic resistance, these peptides could provide new treatment options. They also demonstrate the potential of human proteins in developing new antimicrobials.","specificNumbers":"","methodology":"The study involved in vitro tests and a preclinical mouse model to evaluate the peptides' antimicrobial effects and safety.","limitations":"The study's findings are based on animal models, and further research is needed to confirm efficacy in humans."},{"rthcId":"RPEP-06035","title":"Seafood Paramyosins as Sources of Anti-Angiotensin-Converting-Enzyme and Anti-Dipeptidyl-Peptidase Peptides after Gastrointestinal Digestion: A Cheminformatic Investigation.","authors":"Chai, Tsun-Thai; Wong, Clara Chia-Ci; Sabri, Mohamad Zulkeflee; Wong, Fai-Chu","year":2022,"journal":"Molecules (Basel, Switzerland), 27(12)","doi":"10.3390/molecules27123864","pmid":"35744987","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"2853 fragments were released from seafood paramyosins, including 26 known anti-ACE and 53 anti-DPP-IV peptides.","whyItMatters":"Identifying safe and effective peptides from seafood could lead to new dietary strategies for managing blood pressure and diabetes. This research opens avenues for developing functional foods with health benefits.","specificNumbers":"","methodology":"The study used in silico methods to simulate gastrointestinal digestion of seafood paramyosins and identify potential bioactive peptides.","limitations":"The study is based on in silico analysis, which may not fully replicate biological processes in humans."},{"rthcId":"RPEP-06036","title":"Development of antigen-prediction algorithm for personalized neoantigen vaccine using human leukocyte antigen transgenic mouse.","authors":"Charneau, Jimmy; Suzuki, Toshihiro; Shimomura, Manami; Fujinami, Norihiro; Mishima, Yuji; Hiranuka, Kazushi; Watanabe, Noriko; Yamada, Takashi; Nakamura, Norihiro; Nakatsura, Tetsuya","year":2022,"journal":"Cancer science, 113(4), 1113-1124","doi":"10.1111/cas.15291","pmid":"35122353","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The prediction pipeline selected 278 neoepitopes from tumor tissues of 46 patients with hepatocellular carcinoma or colorectal carcinoma metastases. Validation in HLA-A2, A24, B35, and B07 transgenic mice using ELISpot and killing assays demonstrated that the algorithm predicted immunogenic neopeptides with an area under the curve of 0.687 (p<0.0001).\n\nImportantly, the study showed that short predicted neopeptides are intrinsically present in tumor cells as natural cleavage products of longer peptides, confirming biological relevance. Long peptides containing the predicted neoepitopes also successfully induced cytotoxic T lymphocyte (CTL) responses.","whyItMatters":"Personalized cancer vaccines need to target the right peptides — fragments unique to each patient's tumor. But predicting which mutations will produce effective immune targets has been a major bottleneck. This algorithm and its HLA-transgenic mouse validation platform could accelerate the pipeline from tumor sequencing to vaccine design, bringing personalized cancer immunotherapy closer to routine clinical use.","specificNumbers":"","methodology":"Researchers used a machine learning-based algorithm to analyze somatic mutations in tumor tissues from 46 patients with liver cancer or metastatic colorectal cancer. They selected 278 high-scoring neoepitopes and validated immunogenicity using HLA-transgenic mice (carrying human HLA-A2, A24, B35, and B07). Validation included ELISpot assays to measure immune activation, plus in vitro and in vivo killing assays to confirm cancer cell targeting specificity.","limitations":"The predictive accuracy (AUC=0.687) is above chance but leaves significant room for improvement — roughly a third of predictions may be incorrect. All validation was performed in transgenic mice, which may not perfectly replicate human immune responses. Only four HLA types were tested, while humans carry many more HLA variants. No clinical trial data in humans were presented."},{"rthcId":"RPEP-06037","title":"Recent development of machine learning-based methods for the prediction of defensin family and subfamily.","authors":"Charoenkwan, Phasit; Schaduangrat, Nalini; Mahmud, S M Hasan; Thinnukool, Orawit; Shoombuatong, Watshara","year":2022,"journal":"EXCLI journal, 21, 757-771","doi":"10.17179/excli2022-4913","pmid":"35949489","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Machine learning methods can predict defensin peptide families and subfamilies without needing 3D structural data.","whyItMatters":"Improving the identification of defensin peptides can enhance drug development for immune-related therapies. Efficient prediction methods can save time and resources in research.","specificNumbers":"","methodology":"The study is a comprehensive survey of existing machine learning methods for defensin peptide identification, analyzing various computational approaches.","limitations":"The study primarily focuses on existing methods without developing new models, and results may vary based on dataset quality."},{"rthcId":"RPEP-06038","title":"Effects of Collagen Hydrolysate From Large Hybrid Sturgeon on Mitigating Ultraviolet B-Induced Photodamage.","authors":"Chen, Bei; Yu, Lei; Wu, Jingna; Qiao, Kun; Cui, Lulu; Qu, Haidong; Su, Yongchang; Cai, Shuilin; Liu, Zhiyu; Wang, Qin","year":2022,"journal":"Frontiers in bioengineering and biotechnology, 10, 908033","doi":"10.3389/fbioe.2022.908033","pmid":"35832410","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The low-molecular-weight sturgeon collagen peptides reduced ROS levels and improved collagen content in skin cells.","whyItMatters":"Understanding how marine-derived peptides can protect skin from UV damage could lead to innovative skincare solutions. This research highlights the potential of natural ingredients in cosmetic formulations.","specificNumbers":"","methodology":"The study used response surface methodology to optimize collagen hydrolysis conditions and tested the effects of the resulting peptides on mouse fibroblast cells and zebrafish.","limitations":"The study was conducted in vitro and in animal models, so results may not directly translate to humans."},{"rthcId":"RPEP-06039","title":"iRGD Tumor-Penetrating Peptide-Modified Nano-Delivery System Based on a Marine Sulfated Polysaccharide for Enhanced Anti-Tumor Efficiency Against Breast Cancer.","authors":"Chen, Bowei; Liu, Xiaohong; Li, Yunan; Shan, Tianhe; Bai, Liya; Li, Chunyu; Wang, Yinsong","year":2022,"journal":"International journal of nanomedicine, 17, 617-633","doi":"10.2147/IJN.S343902","pmid":"35173433","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The iRGD-PSS@PBAE@JQ1/ORI nanoparticles significantly enhanced tumor targeting and cellular internalization.","whyItMatters":"This research addresses the limitations of current breast cancer therapies by introducing a novel delivery system that improves drug efficacy. It could pave the way for more effective treatments in the future.","specificNumbers":"","methodology":"The study involved the development and evaluation of a peptide-modified nano-delivery system in both laboratory and animal models.","limitations":"The study primarily focuses on in vitro and in vivo models, and further research is needed to confirm efficacy in human patients."},{"rthcId":"RPEP-06040","title":"Personalized neoantigen vaccine combined with PD-1 blockade increases CD8+ tissue-resident memory T-cell infiltration in preclinical hepatocellular carcinoma models.","authors":"Chen, Hengkai; Li, Zhenli; Qiu, Liman; Dong, Xiuqing; Chen, Geng; Shi, Yingjun; Cai, Linsheng; Liu, Wenhan; Ye, Honghao; Zhou, Yang; Ouyang, Jiahe; Cai, Zhixiong; Liu, Xiaolong","year":2022,"journal":"Journal for immunotherapy of cancer, 10(9)","doi":"10.1136/jitc-2021-004389","pmid":"36113894","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The neoantigen peptide vaccine (NeoVAC) combined with anti-PD-1 immunotherapy demonstrated:\n\n- 80% durable tumor regression in orthotopic (liver-implanted) HCC mouse models\n- Long-term immune memory against the tumor (indicating durable protection against recurrence)\n- Dramatically increased CD8+ tissue-resident memory T cells (TRMs) in the tumor microenvironment\n- CD8+ TRM infiltration positively correlated with treatment efficacy\n- Strong tumor-killing capacity of CD8+ TRMs confirmed both in vitro and in vivo\n- Validated in autologous patient-derived HCC cells (human cancer cells killed by TRMs)\n\nThe vaccine consisted of seven immunogenic neoantigen peptides with clinical-grade Poly(I:C) adjuvant. Single-cell RNA sequencing revealed the immune mechanisms underlying the synergistic effect.","whyItMatters":"Hepatocellular carcinoma is the third leading cause of cancer death worldwide, and most patients are diagnosed too late for surgery. Current immunotherapy (PD-1 blockade alone) has limited response rates in liver cancer. This study shows that combining a personalized peptide vaccine with immunotherapy dramatically improves outcomes by recruiting specialized immune cells that remain in the liver long-term. The 80% regression rate and evidence of immune memory are exceptional for an aggressive cancer.","specificNumbers":"","methodology":"Neoantigen peptides were identified through tumor mutation screening of the murine Hepa1-6 HCC cell line. Seven high-immunogenicity peptides were selected and combined with clinical-grade Poly(I:C) adjuvant to create NeoVAC. Efficacy was tested in an orthotopic (liver-implanted) HCC mouse model, alone and combined with anti-PD-1 antibody. The tumor immune microenvironment was analyzed by single-cell RNA sequencing, tetramer flow cytometry, and immunofluorescence. Tumor-killing capacity of CD8+ TRMs was verified in both mouse and human patient-derived cancer cells.","limitations":"All efficacy data are from mouse models, which may not predict human responses. The orthotopic model uses a single mouse cell line (Hepa1-6), limiting diversity. Patient-derived cell validation was done in vitro, not in patients. The seven neoantigen peptides are specific to the mouse tumor line — human patients would require individualized peptide selection. Manufacturing personalized vaccines for each patient is logistically complex and expensive. Long-term durability of the immune response was not assessed beyond the study timeframe."},{"rthcId":"RPEP-06041","title":"Lipid nanoparticle-mediated lymph node-targeting delivery of mRNA cancer vaccine elicits robust CD8+ T cell response.","authors":"Chen, Jinjin; Ye, Zhongfeng; Huang, Changfeng; Qiu, Min; Song, Donghui; Li, Yamin; Xu, Qiaobing","year":2022,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 119(34), e2207841119","doi":"10.1073/pnas.2207841119","pmid":"35969778","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The lipid nanoparticle 113-O12B led to a 40% complete response in tumor models when combined with anti-PD-1 therapy.","whyItMatters":"Targeted delivery of mRNA vaccines can minimize side effects and maximize immune responses, potentially leading to more effective cancer treatments.","specificNumbers":"","methodology":"The study used a lipid nanoparticle to deliver mRNA to lymph nodes in mouse models and assessed immune responses and tumor inhibition.","limitations":"The study was conducted in mouse models, and results may not directly translate to humans."},{"rthcId":"RPEP-06042","title":"Safety and efficacy of Thymosin α1 in the treatment of hepatitis B virus-related acute-on-chronic liver failure: a randomized controlled trial.","authors":"Chen, Jun-Feng; Chen, Shu-Ru; Lei, Zi-Ying; Cao, Hui-Juan; Zhang, Shao-Quan; Weng, Wei-Zhen; Xiong, Jing; Lin, Deng-Na; Zhang, Jing; Zheng, Yu-Bao; Gao, Zhi-Liang; Lin, Bing-Liang","year":2022,"journal":"Hepatology international, 16(4), 775-788","doi":"10.1007/s12072-022-10335-6","pmid":"35616850","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The Tα1 group had a 90-day liver transplantation-free survival rate of 75.0% compared to 53.4% in the SMT group.","whyItMatters":"These findings suggest that Tα1 could be a valuable treatment option for improving outcomes in patients with severe liver failure due to hepatitis B. Reducing infection rates is crucial for enhancing patient survival.","specificNumbers":"","methodology":"This was an open-label, randomized controlled trial involving 120 patients with HBV-related acute-on-chronic liver failure.","limitations":"The study was open-label and may have biases; further research is needed to confirm long-term effects and benefits in diverse populations."},{"rthcId":"RPEP-06043","title":"Design of stapled peptide-based PROTACs for MDM2/MDMX atypical degradation and tumor suppression.","authors":"Chen, Si; Li, Xiang; Li, Yinghua; Yuan, Xing; Geng, Chenchen; Gao, Songyan; Li, Jinyang; Ma, Bohan; Wang, Zhe; Lu, Wuyuan; Hu, Hong-Gang","year":2022,"journal":"Theranostics, 12(15), 6665-6681","doi":"10.7150/thno.75444","pmid":"36185610","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The optimized stapled peptide-PROTAC hybrid SPMI-HIF2-1 showed similar binding affinity for both MDM2 and MDMX compared to its linear counterpart, but with higher helical content, improved proteolytic stability, better cellular permeability, and improved pharmacokinetics. In subcutaneous and orthotopic colorectal cancer xenograft models, SPMI-HIF2-1 effectively killed cancer cells and inhibited tumor progression through simultaneous atypical degradation of both MDM2 and MDMX, leading to durable p53 activation. Structural analysis confirmed the molecule simultaneously bound the target protein and E3 ligase in a ternary complex.","whyItMatters":"p53 is mutated or inactivated in more than half of all human cancers, and reactivating it is one of the most pursued goals in oncology. Previous approaches using peptide inhibitors of MDM2/MDMX were limited by poor stability and the rapid rebound of target proteins. SP-PROTACs solve both problems — they're stable enough to reach cancer cells and they permanently destroy (rather than just inhibit) the cancer proteins. This 'degrade rather than inhibit' paradigm could produce longer-lasting anticancer effects.","specificNumbers":"","methodology":"Researchers designed a series of stapled peptide-based PROTACs (SP-PROTACs) based on the PMI peptide, which has dual specificity for MDM2 and MDMX. They characterized binding affinity (fluorescence polarization assays), structural properties (helical content), proteolytic stability, cellular permeability, and pharmacokinetics. Anticancer efficacy was tested in both subcutaneous and orthotopic colorectal cancer xenograft mouse models. Structural modeling analyzed the ternary complex formation.","limitations":"All efficacy testing was in mouse xenograft models using human colorectal cancer cells, which may not fully predict human responses. The pharmacokinetic improvements over linear peptides, while significant, still may not be sufficient for clinical use without further optimization. The atypical degradation mechanism needs further characterization. No toxicity or safety data were reported beyond tumor models. Clinical translation of stapled peptide-PROTACs faces manufacturing and formulation challenges."},{"rthcId":"RPEP-06044","title":"\"Sibling\" battle or harmony: crosstalk between nesfatin-1 and ghrelin.","authors":"Chen, Xi; Dong, Jing; Jiao, Qian; Du, Xixun; Bi, Mingxia; Jiang, Hong","year":2022,"journal":"Cellular and molecular life sciences : CMLS, 79(3), 169","doi":"10.1007/s00018-022-04193-6","pmid":"35239020","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Nesfatin-1 and ghrelin have opposing effects on energy metabolism and glucose regulation, but similar anti-inflammatory and neuroprotective effects.","whyItMatters":"Understanding the interplay between these two peptides could lead to new insights into metabolic regulation and potential therapeutic targets for metabolic disorders.","specificNumbers":"","methodology":"The study compares the effects of nesfatin-1 and ghrelin on various physiological functions.","limitations":"The study primarily focuses on the comparative effects of the peptides without identifying the receptor for nesfatin-1."},{"rthcId":"RPEP-06045","title":"GLP-1 mimetics as a potential therapy for nonalcoholic steatohepatitis.","authors":"Chen, Yan; Xu, Ying-Na; Ye, Chen-Yu; Feng, Wen-Bo; Zhou, Qing-Tong; Yang, De-Hua; Wang, Ming-Wei","year":2022,"journal":"Acta pharmacologica Sinica, 43(5), 1156-1166","doi":"10.1038/s41401-021-00836-9","pmid":"34934197","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 mimetics may provide therapeutic benefits for NASH management.","whyItMatters":"NASH is a growing health concern linked to obesity and diabetes, and effective treatments are needed. GLP-1 mimetics could offer new therapeutic avenues for managing this condition.","specificNumbers":"","methodology":"The article reviews existing literature on the pathophysiology and treatment options for NASH, focusing on GLP-1 mimetics.","limitations":"The study is a review and does not present original experimental data or clinical trial results."},{"rthcId":"RPEP-06046","title":"Effects of niacin on intestinal epithelial Barrier, intestinal Immunity, and microbial community in weaned piglets challenged by PDCoV.","authors":"Chen, Yibo; Li, Ping; Zhen, Rui; Wang, Li; Feng, Junsen; Xie, Yongsheng; Yang, Bijing; Xiong, Yunxia; Niu, Jiawei; Wu, Qiwen; Jiang, Zongyong; He, Dongsheng; Yi, Hongbo","year":2022,"journal":"International immunopharmacology, 111, 109054","doi":"10.1016/j.intimp.2022.109054","pmid":"35921778","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Niacin reduced diarrhea and intestinal damage in PDCoV-infected piglets, improving gut health and immune response.","whyItMatters":"Understanding how niacin can support intestinal health in piglets could lead to better management strategies in livestock, especially during viral outbreaks.","specificNumbers":"","methodology":"Fifteen weaned piglets were divided into three groups: control, PDCoV-infected, and PDCoV-infected with niacin treatment for three days.","limitations":"The study was conducted on a small sample size of 15 piglets, which may limit the generalizability of the findings."},{"rthcId":"RPEP-06047","title":"Antiviral Effect of hBD-3 and LL-37 during Human Primary Keratinocyte Infection with West Nile Virus.","authors":"Chessa, Céline; Bodet, Charles; Jousselin, Clément; Larivière, Andy; Damour, Alexia; Garnier, Julien; Lévêque, Nicolas; Garcia, Magali","year":2022,"journal":"Viruses, 14(7)","doi":"10.3390/v14071552","pmid":"35891533","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"LL-37 reduced viral load in infected keratinocytes, while hBD-3 did not inhibit WNV replication.","whyItMatters":"Understanding how these peptides work could lead to new antiviral therapies for flavivirus infections. This research contributes to the growing field of antimicrobial peptides in viral defense.","specificNumbers":"","methodology":"The study assessed the effects of LL-37 and hBD-3 on WNV infection in human primary keratinocytes through viral load measurements.","limitations":"The study was conducted in vitro, so results may not directly translate to human responses in vivo."},{"rthcId":"RPEP-06048","title":"Vincristine increased spinal cord substance P levels in a peripheral neuropathy rat model.","authors":"Chiba, Terumasa; Kambe, Toshie; Yamamoto, Ken; Kawakami, Kazuyoshi; Taguchi, Kyoji; Abe, Kenji","year":2022,"journal":"Drug and chemical toxicology, 45(1), 393-397","doi":"10.1080/01480545.2019.1706547","pmid":"31899978","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Vincristine treatment (0.1 mg/kg/day i.p. for 14 days) significantly increased substance P expression by 30.3% ± 2.4% in the superficial layers of the rat spinal dorsal horn compared to saline controls, confirmed by both immunohistochemistry and direct measurement of substance P levels in spinal cord tissue.\n\nThe neurokinin 1 (NK1) receptor antagonist aprepitant (20 mg/kg, s.c.) significantly inhibited the mechanical allodynia and hyperalgesia caused by vincristine, demonstrating that substance P signaling through the NK1 receptor is a key mediator of this chemotherapy-induced neuropathic pain.","whyItMatters":"Chemotherapy-induced peripheral neuropathy affects many cancer patients and is a major reason for dose reductions or treatment discontinuation. Understanding that substance P — a well-known pain peptide — mediates vincristine-induced pain opens the door to using existing NK1 receptor antagonists like aprepitant (already FDA-approved for nausea) as potential treatments for this debilitating side effect.","specificNumbers":"","methodology":"Sprague-Dawley rats received intraperitoneal vincristine at 0.1 mg/kg/day. After 14 days, mechanical pain sensitivity was assessed using von Frey filaments to measure allodynia and hyperalgesia. Substance P expression in the spinal dorsal horn was quantified using immunohistochemistry, and substance P levels in spinal cord tissue were measured directly. The NK1 receptor antagonist aprepitant was administered subcutaneously to test whether blocking substance P signaling could reduce the pain.","limitations":"The study was conducted in rats, so the findings may not directly translate to human chemotherapy patients. Specific group sizes were not reported in the abstract. The study only examined vincristine, so results may not apply to other chemotherapy drugs that cause neuropathy. Long-term effects of aprepitant on neuropathic pain and potential interactions with cancer treatment were not assessed."},{"rthcId":"RPEP-06049","title":"Desmopressin therapy in children and adults: pharmacological considerations and clinical implications.","authors":"Chin, Xinyi; Teo, Shao Wei; Lim, Soo Ting; Ng, Yong Hong; Han, How Chuan; Yap, Fabian","year":2022,"journal":"European journal of clinical pharmacology, 78(6), 907-917","doi":"10.1007/s00228-022-03297-z","pmid":"35199198","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06050","title":"Supramolecular Peptide Nanofiber/PLGA Nanocomposites for Enhancing Pulmonary Drug Delivery.","authors":"Chintapula, Uday; Yang, Su; Nguyen, Trinh; Li, Yang; Jaworski, Justyn; Dong, He; Nguyen, Kytai T","year":2022,"journal":"ACS applied materials & interfaces, 14(51), 56498-56509","doi":"10.1021/acsami.2c15204","pmid":"36475601","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The peptide nanofiber-coated PLGA nanocomposites demonstrated dramatically enhanced cellular uptake: 3-fold higher delivery into primary lung epithelial cells and macrophages, and 10-fold higher delivery into endothelial cells compared to naked PLGA nanoparticles. Compared to nanoparticles modified with traditional monomeric cell-penetrating peptides, the nanofiber-coated version still showed 2-fold improvement.\n\nMechanistic studies indicated that the nanocomposites enter cells through mixed macropinocytosis and passive energy-independent mechanisms, with endosomal escape occurring within 24 hours. The composites also demonstrated potent mucus permeation. The formulation survived freeze-drying and nebulization without losing physicochemical or biological activity, supporting translational potential as an inhaled therapeutic system.","whyItMatters":"Pulmonary drug delivery is one of the most important frontiers in medicine — from treating asthma and COPD to delivering gene therapies for cystic fibrosis and mRNA therapeutics for respiratory infections. Current nanoparticle systems are limited by poor mucus penetration and cellular uptake. By leveraging the self-assembling properties of cell-penetrating peptides to create a nanofiber coating, this approach provides a significant upgrade to standard PLGA nanoparticles with proven translational characteristics.","specificNumbers":"","methodology":"Supramolecular cell-penetrating peptides (CPPs) that self-assemble into nanofibers were coated onto PLGA nanoparticles to create nanocomposites. Cellular uptake was quantified in primary lung epithelial cells, macrophages, and endothelial cells and compared to naked PLGA and monomeric CPP-modified nanoparticles. Cell entry mechanisms were investigated through inhibitor studies. Mucus permeation was assessed. The formulation was tested for stability after freeze-drying and nebulization.","limitations":"All studies are in vitro — no animal inhalation studies or in vivo pulmonary delivery data are presented. The 10-fold enhancement was in endothelial cells, while lung epithelial cells showed a more modest 3-fold improvement. The specific cell-penetrating peptide sequences used are not detailed in the abstract. Long-term stability of the freeze-dried formulation and potential immunogenicity of the peptide nanofibers in the lungs are not addressed. The drug payload capacity and release kinetics with actual therapeutic cargo are not characterized."},{"rthcId":"RPEP-06051","title":"Nuclear receptor estrogen-related receptor modulates antimicrobial peptide expression for host innate immunity in Tribolium castaneum.","authors":"Choi, Byungyoon; Park, Woo-Ram; Kim, Yu-Ji; Mun, Seulgi; Park, Su-Jin; Jeong, Jae-Ho; Choi, Hueng-Sik; Kim, Don-Kyu","year":2022,"journal":"Insect biochemistry and molecular biology, 148, 103816","doi":"10.1016/j.ibmb.2022.103816","pmid":"35926689","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"ERR-deficient larvae showed increased bacterial load and reduced survival after E. coli infection.","whyItMatters":"Understanding how ERR regulates immune responses in insects can provide insights into insect biology and potential pest control strategies. It may also inform research on innate immunity in other organisms.","specificNumbers":"","methodology":"The study used RNA sequencing and chromatin immunoprecipitation to analyze gene expression and protein interactions in T. castaneum.","limitations":"The study focuses on a specific insect model, which may limit the generalizability of the findings to other species."},{"rthcId":"RPEP-06052","title":"Innate immunity and microbial dysbiosis in hidradenitis suppurativa - vicious cycle of chronic inflammation.","authors":"Chopra, Divya; Arens, Rachel A; Amornpairoj, Watcharee; Lowes, Michelle A; Tomic-Canic, Marjana; Strbo, Natasa; Lev-Tov, Hadar; Pastar, Irena","year":2022,"journal":"Frontiers in immunology, 13, 960488","doi":"10.3389/fimmu.2022.960488","pmid":"35967376","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Dysregulation of antimicrobial peptides and complement system linked to HS pathology.","whyItMatters":"Understanding the interplay between the immune system and bacteria in HS may lead to better treatment strategies. This could improve the quality of life for those suffering from this chronic condition.","specificNumbers":"","methodology":"The study reviews existing literature on the immune response and microbiome in HS.","limitations":"The study primarily reviews existing literature, which may not provide new experimental data."},{"rthcId":"RPEP-06053","title":"Real-World Comparative Evaluation of Add-On Glucagon-like Peptide 1 Receptor Agonist in Type 2 Diabetes Treated with or without Insulin.","authors":"Chou, Hsuan-Wen; Cheng, Kai-Pi; Lin, An-Chi; Hung, Hao-Chang; Lin, Ching-Han; Wang, Chih-Chen; Wu, Hung-Tsung; Ou, Horng-Yih","year":2022,"journal":"Pharmaceuticals (Basel, Switzerland), 15(12)","doi":"10.3390/ph15121569","pmid":"36559020","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Insulin users had a HbA1C reduction of −1.17% compared to −0.76% in non-insulin users (p = 0.018).","whyItMatters":"Understanding how GLP-1 RAs work in different patient groups can help optimize diabetes management strategies. This knowledge may lead to better treatment plans for those with type 2 diabetes.","specificNumbers":"","methodology":"A retrospective study involving 358 patients with type 2 diabetes who initiated GLP-1 RA treatment.","limitations":"The study is retrospective and may be subject to biases inherent in such designs. Additionally, the findings may not be generalizable to all populations."},{"rthcId":"RPEP-06054","title":"Rational design of amphiphilic fluorinated peptides: evaluation of self-assembly properties and hydrogel formation.","authors":"Chowdhary, Suvrat; Schmidt, Robert Franz; Sahoo, Anil Kumar; Tom Dieck, Tiemo; Hohmann, Thomas; Schade, Boris; Brademann-Jock, Kerstin; Thünemann, Andreas F; Netz, Roland R; Gradzielski, Michael; Koksch, Beate","year":2022,"journal":"Nanoscale, 14(28), 10176-10189","doi":"10.1039/d2nr01648f","pmid":"35796261","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Increased fluorination promotes peptide fibrillation and hydrogel formation.","whyItMatters":"Understanding how fluorination affects peptide behavior can lead to improved biomaterials for pharmaceuticals and biotechnology. This could enhance drug delivery systems and tissue engineering.","specificNumbers":"","methodology":"The study involved designing amphipathic peptides with varying fluorination levels and assessing their self-assembly and hydrogel properties through molecular simulations.","limitations":"The study primarily focuses on in vitro conditions, which may not fully represent biological systems in vivo."},{"rthcId":"RPEP-06055","title":"Transcriptional and functional analyses of neoantigen-specific CD4 T cells during a profound response to anti-PD-L1 in metastatic Merkel cell carcinoma.","authors":"Church, Candice; Pulliam, Thomas; Longino, Natalie; Park, Song Y; Smythe, Kimberly S; Makarov, Vladimir; Riaz, Nadeem; Jing, Lichen; Amezquita, Robert; Campbell, Jean S; Gottardo, Raphael; Pierce, Robert H; Choi, Jaehyuk; Chan, Timothy A; Koelle, David M; Nghiem, Paul","year":2022,"journal":"Journal for immunotherapy of cancer, 10(9)","doi":"10.1136/jitc-2022-005328","pmid":"36252564","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Neoantigen-specific CD4 T cells were undetectable before therapy but became detectable after anti-PD-L1 treatment.","whyItMatters":"Understanding the role of CD4 T cells in cancer treatment could enhance immunotherapy strategies for Merkel cell carcinoma and potentially other cancers.","specificNumbers":"","methodology":"The study utilized whole exome sequencing, T cell assays, and single-cell RNA sequencing to analyze T cell responses.","limitations":"The study is based on a single patient, which may limit the generalizability of the findings."},{"rthcId":"RPEP-06056","title":"Semaglutide might be a key for breaking the vicious cycle of metabolically associated fatty liver disease spectrum?","authors":"Cigrovski Berkovic, Maja; Rezic, Tanja; Bilic-Curcic, Ines; Mrzljak, Anna","year":2022,"journal":"World journal of clinical cases, 10(20), 6759-6768","doi":"10.12998/wjcc.v10.i20.6759","pmid":"36051145","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide may provide benefits for managing MAFLD, though more research is needed.","whyItMatters":"Finding effective treatments for MAFLD is crucial as it can lead to serious liver complications. Semaglutide's potential role could change management strategies for this condition.","specificNumbers":"","methodology":"This is an opinion review discussing existing data on semaglutide's effects on MAFLD.","limitations":"The review is opinion-based and does not present original research data; further clinical trials are needed."},{"rthcId":"RPEP-06057","title":"Safety Profile of Bremelanotide Across the Clinical Development Program.","authors":"Clayton, Anita H; Kingsberg, Sheryl A; Portman, David; Sadiq, Amama; Krop, Julie; Jordan, Robert; Lucas, Johna; Simon, James A","year":2022,"journal":"Journal of women's health (2002), 31(2), 171-182","doi":"10.1089/jwh.2021.0191","pmid":"35147466","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06058","title":"Once-weekly 2.4 mg Semaglutide for Weight Management in Obesity: A Game Changer?","authors":"Colin, Ides M; Gérard, Katherine M","year":2022,"journal":"TouchREVIEWS in endocrinology, 18(1), 35-42","doi":"10.17925/EE.2022.18.1.35","pmid":"35949360","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide provides clinically meaningful weight loss, exceeding previous pharmacotherapies.","whyItMatters":"This treatment represents a significant advancement in obesity management, potentially reducing obesity-related health risks. It offers a new, effective option for individuals struggling with weight loss.","specificNumbers":"","methodology":"The study reviews data from phase II and III clinical trials on semaglutide and compares it with other treatments.","limitations":"The study primarily focuses on clinical trial data, which may not fully represent real-world effectiveness."},{"rthcId":"RPEP-06059","title":"Challenges and new opportunities for detecting endogenous opioid peptides in reward.","authors":"Conway, Sineadh M; Mikati, Marwa O; Al-Hasani, Ream","year":2022,"journal":"Addiction neuroscience, 2","doi":"10.1016/j.addicn.2022.100016","pmid":"35693759","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review catalogs the challenges of endogenous opioid peptide research:\n\n- Over 20 unique opioid peptides derived from 4 precursor molecules (proopiomelanocortin, proenkephalin, prodynorphin, pronociceptin)\n- Low in vivo concentrations make detection difficult\n- Complex processing and release dynamics complicate interpretation\n- Traditional techniques (microdialysis, RIA, tissue-level measurements) have significant limitations for real-time behavioral studies\n\nNew techniques — including genetically encoded sensors, advanced mass spectrometry, and improved microdialysis methods — are beginning to overcome these barriers and enable direct measurement of specific opioid peptides during behavioral manipulations.","whyItMatters":"The opioid crisis has killed hundreds of thousands, yet we still don't fully understand how the brain's own opioid system works. Each opioid peptide may have distinct roles in pleasure, motivation, and addiction, but we've been unable to tell them apart in the living brain. New detection tools could finally reveal which specific peptides drive different aspects of addiction, potentially leading to more targeted treatments that don't disrupt the entire opioid system.","specificNumbers":"","methodology":"Narrative review surveying traditional and emerging techniques for measuring endogenous opioid peptides in the context of food and drug reward research. Covers direct measurement approaches (microdialysis, mass spectrometry) and indirect approaches (optogenetics, pharmacology, genetic tools).","limitations":"This is a review article that does not present original data. Many of the newer techniques described are still in early development and have not been widely adopted. The review focuses primarily on food and drug reward contexts and does not comprehensively cover other opioid peptide functions (pain, mood, social bonding). Some emerging tools may have their own limitations in sensitivity, specificity, or temporal resolution."},{"rthcId":"RPEP-06060","title":"Melanocortin Signaling Connecting Systemic Metabolism With Mood Disorders.","authors":"Copperi, Francesca; Kim, Jung Dae; Diano, Sabrina","year":2022,"journal":"Biological psychiatry, 91(10), 879-887","doi":"10.1016/j.biopsych.2021.05.026","pmid":"34344535","tags":[],"studyType":"review","evidenceStrength":"moderate","keyFinding":"The central melanocortin system — a brain circuitry driven by POMC, AgRP, and neuropeptide Y peptides acting on melanocortin receptors — plays a dual role in regulating both feeding behavior and mood. This shared circuitry may explain why obesity and depression so often co-occur.\n\nThe review highlights that DSM-5 recognizes two depression subtypes with opposite metabolic profiles: melancholic depression (decreased appetite, weight loss) and atypical depression (hyperphagia, weight gain, fatigue). Melanocortin signaling appears to be involved in both patterns, suggesting it acts as a biological bridge between metabolic state and emotional regulation.","whyItMatters":"Depression and obesity affect hundreds of millions of people worldwide and frequently overlap in the same patients. Understanding that shared peptide signaling circuits drive both conditions could lead to treatments that address metabolism and mood simultaneously, rather than treating each in isolation.","specificNumbers":"Review article — synthesizes evidence across human and animal model studies","methodology":"This is a narrative review examining the published literature on the melanocortin system's role in feeding and mood regulation, drawing from both human clinical data and animal model research. The authors synthesized evidence on POMC, AgRP, neuropeptide Y, and melanocortin receptors (MC3R, MC4R) across behavioral, metabolic, and psychiatric domains.","limitations":"As a narrative review, this paper synthesizes existing findings rather than presenting new experimental data. The melanocortin circuits linking mood and feeding are not yet fully mapped, and much of the evidence comes from animal models that may not directly translate to humans. The review acknowledges that the system's complexity means current understanding is incomplete."},{"rthcId":"RPEP-06061","title":"An antibody-free, ultrafiltration-based assay for the detection of growth hormone-releasing hormones in urine at low pg/mL concentrations using nanoLC-HRMS/MS.","authors":"Coppieters, Gilles; Deventer, Koen; Polet, Michaël; Van Eenoo, Peter; Judák, Péter","year":2022,"journal":"Journal of pharmaceutical and biomedical analysis, 214, 114726","doi":"10.1016/j.jpba.2022.114726","pmid":"35298973","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The method achieved limits of detection between 5 and 25 pg/mL and limits of identification between 25 and 50 pg/mL.","whyItMatters":"This method simplifies the detection of prohibited hormones, potentially improving drug testing protocols. It also opens avenues for future research on emerging peptide drugs.","specificNumbers":"","methodology":"The study utilized an ultrafiltration-based approach combined with nanoLC-HRMS/MS for sample analysis.","limitations":"The study primarily focuses on urine samples, and results may not directly translate to other biological matrices."},{"rthcId":"RPEP-06062","title":"Intraoperative abobotulinumtoxinA alleviates pain after surgery and improves general wellness in a translational animal model.","authors":"Cornet, Sylvie; Carré, Denis; Limana, Lorenzo; Castel, David; Meilin, Sigal; Horne, Ron; Pons, Laurent; Evans, Steven; Lezmi, Stephane; Kalinichev, Mikhail","year":2022,"journal":"Scientific reports, 12(1), 21555","doi":"10.1038/s41598-022-25002-x","pmid":"36513684","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"At Day 1, partial reversal of mechanical allodynia was observed in aboBoNT-A groups, with full reversal by Day 3.","whyItMatters":"Post-surgical pain management is crucial for recovery, and this study suggests that aboBoNT-A could offer a new therapeutic option. Understanding its mechanisms may lead to better pain relief strategies.","specificNumbers":"","methodology":"The study involved a surgical model in pigs, with intradermal injections of aboBoNT-A or controls, followed by assessments of pain responses and tissue analysis.","limitations":"The study was conducted in a pig model, which may not fully translate to human patients. Further clinical trials are needed."},{"rthcId":"RPEP-06063","title":"Amylin Pharmacology in Alzheimer's Disease Pathogenesis and Treatment.","authors":"Corrigan, Rachel R; Piontkivska, Helen; Casadesus, Gemma","year":2022,"journal":"Current neuropharmacology, 20(10), 1894-1907","doi":"10.2174/1570159X19666211201093147","pmid":"34852745","tags":["amylin","neurodegenerative-disease"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Amylin presents a pharmacological paradox in Alzheimer's disease research. On one hand, the pancreatic peptide self-aggregates into amyloid deposits — similar to amyloid-beta in AD brains — and has been implicated as a pathogenic factor in both type 2 diabetes and Alzheimer's. On the other hand, multiple studies show that amylin and its synthetic analog pramlintide (already FDA-approved for diabetes) have neuroprotective effects against Alzheimer's pathology.\n\nThis review argues that amylin receptor signaling in the central nervous system is far more complex than the simple \"toxic aggregation\" model suggests, and that pharmacological modulation of amylin receptors could be therapeutically beneficial for Alzheimer's — much as it already is for diabetes. The challenge is resolving how the same peptide can be both pathogenic and protective depending on context.","whyItMatters":"The link between type 2 diabetes and Alzheimer's disease is well established — diabetics have roughly double the risk of developing AD. Amylin sits at the intersection of these two diseases, making it a uniquely important research target. If the neuroprotective effects of amylin receptor signaling can be harnessed while avoiding the toxic aggregation, existing diabetes drugs like pramlintide could potentially be repurposed for Alzheimer's treatment — a much faster path to therapy than developing new drugs from scratch.","specificNumbers":"","methodology":"Comprehensive narrative review of published research on amylin receptor signaling, amylin's role in both type 2 diabetes and Alzheimer's disease, and the neuroprotective versus neurotoxic effects of amylin and pramlintide in the central nervous system.","limitations":"This is a narrative review synthesizing a complex and sometimes contradictory literature. Many of the neuroprotective findings come from animal models that may not fully replicate human Alzheimer's disease. The amylin receptor signaling system in the brain is not well characterized, making mechanistic conclusions tentative. No clinical trial data exists for amylin-based Alzheimer's therapies."},{"rthcId":"RPEP-06064","title":"Anorectic and aversive effects of GLP-1 receptor agonism are mediated by brainstem cholecystokinin neurons, and modulated by GIP receptor activation.","authors":"Costa, Alessia; Ai, Minrong; Nunn, Nicolas; Culotta, Isabella; Hunter, Jenna; Boudjadja, Mehdi Boutagouga; Valencia-Torres, Lourdes; Aviello, Gabriella; Hodson, David J; Snider, Brandy M; Coskun, Tamer; Emmerson, Paul J; Luckman, Simon M; D'Agostino, Giuseppe","year":2022,"journal":"Molecular metabolism, 55, 101407","doi":"10.1016/j.molmet.2021.101407","pmid":"34844019","tags":["glp-1-receptor-agonists","neuropeptides"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Using genetic tools to manipulate specific neuron populations in mice, researchers showed that CCK-expressing neurons in the caudal brainstem are required for the full appetite-suppressing and body weight-lowering effects of the GLP-1 receptor agonist exendin-4. These same neurons also mediate conditioned taste avoidance — the animal model equivalent of nausea.\n\nWhile these CCK neurons don't directly express GIP receptors, activating GIP receptors elsewhere reduced the recruitment of these GLP-1-responsive brainstem neurons. This resulted in a selective reduction of conditioned taste avoidance (nausea proxy) while preserving appetite suppression. The key neuroanatomical findings were confirmed in non-human primate brain tissue, supporting translational relevance.","whyItMatters":"Nausea is the number one reason patients discontinue GLP-1 drugs. This study provides the first clear neuronal mechanism explaining why GLP-1 agonists cause nausea and — more importantly — why adding GIP receptor activation (as in tirzepatide) may reduce it. The finding that GIP selectively dampens the aversive response without eliminating appetite suppression provides a biological rationale for dual agonist drug design and could guide the development of next-generation obesity drugs with better tolerability profiles.","specificNumbers":"CCK brainstem neurons required for full anorectic effect; GIP activation selectively reduces conditioned taste avoidance; key findings confirmed in non-human primate brain","methodology":"The researchers combined neuroanatomical mapping, genetic manipulation of specific neuron populations, and behavioral testing in mice. They used chemogenetics and neuron-specific ablation to test whether brainstem CCK neurons were necessary for GLP-1 agonist effects. They also administered GIP receptor agonists alongside exendin-4 to determine how GIP modulates GLP-1-responsive neurons. Key neuroanatomical findings (the presence and distribution of CCK neurons in the brainstem) were validated in non-human primate brain sections.","limitations":"Conditioned taste avoidance in mice is a proxy for human nausea but not a perfect equivalent — mice can't report feeling nauseous. The study used exendin-4 rather than longer-acting GLP-1 drugs like semaglutide or liraglutide. While neuroanatomical findings were confirmed in non-human primates, the functional experiments were all in mice. Human brainstem circuitry may have additional complexity not captured by these models."},{"rthcId":"RPEP-06065","title":"Detection of insulin analogues and large peptides >2 kDa in urine.","authors":"Cox, Holly D; Knussmann, Graham N; Moore, Chad; Eichner, Daniel","year":2022,"journal":"Drug testing and analysis, 14(7), 1264-1272","doi":"10.1002/dta.3249","pmid":"35261185","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The limit of detection for insulin analogues is 5-25 pg/ml; for other peptides, it's 5-50 pg/ml.","whyItMatters":"Improving detection methods for banned substances can help maintain fair competition in sports. This research contributes to anti-doping efforts by providing a reliable way to identify performance-enhancing drugs.","specificNumbers":"","methodology":"The study used ultrafiltration and solid phase extraction followed by detection via a triple quadrupole mass spectrometer.","limitations":"The study primarily focuses on urine samples, and results may not directly translate to other biological matrices or human applications."},{"rthcId":"RPEP-06066","title":"Recent Advances in Oral Peptide or Protein-Based Drug Liposomes.","authors":"Cui, Jian; Wen, Zhiwei; Zhang, Wei; Wu, Wei","year":2022,"journal":"Pharmaceuticals (Basel, Switzerland), 15(9)","doi":"10.3390/ph15091072","pmid":"36145293","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Improved liposome formulations can enhance the stability and absorption of peptide drugs.","whyItMatters":"Enhancing the oral bioavailability of peptide drugs can lead to more effective treatments and improved patient compliance. This research could pave the way for new oral medications.","specificNumbers":"","methodology":"The article reviews various strategies for liposome preparation and surface modification.","limitations":"The review does not provide experimental data but rather summarizes existing strategies."},{"rthcId":"RPEP-06067","title":"Antioxidant peptides derived from hydrolyzed milk proteins by Lactobacillus strains: A BIOPEP-UWM database-based analysis.","authors":"Cui, Lei; Yang, Guo; Lu, Shuyi; Zeng, Xiaoqun; He, Jun; Guo, Yuxing; Pan, Daodong; Wu, Zhen","year":2022,"journal":"Food research international (Ottawa, Ont.), 156, 111339","doi":"10.1016/j.foodres.2022.111339","pmid":"35651087","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The peptide VKEAMAPK showed IC50 values of 0.63 mg/mL and 0.86 mg/mL in DPPH and ABTS assays, respectively.","whyItMatters":"Understanding the antioxidant properties of milk-derived peptides can enhance the nutritional value of dairy products. This research supports the development of functional foods that promote health.","specificNumbers":"","methodology":"The study involved hydrolyzing casein and whey proteins using Lactobacillus strains and analyzing the resulting peptides with LC-MS/MS.","limitations":"The study primarily focuses on in vitro results, which may not fully translate to in vivo effects in humans."},{"rthcId":"RPEP-06068","title":"Overview on effectiveness of erenumab, fremanezumab, and galcanezumab in reducing medication overuse headache in chronic migraine patients.","authors":"Curone, Marcella; Tullo, Vincenzo; Didier, Henri Albert; Bussone, Gennaro","year":2022,"journal":"Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 43(9), 5759-5761","doi":"10.1007/s10072-022-06265-8","pmid":"35836032","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"80% of patients showed a ≥50% reduction in headache days and medication use at 3 months.","whyItMatters":"Understanding the effectiveness of these treatments can help improve quality of life for patients suffering from chronic migraines and medication overuse headache.","specificNumbers":"","methodology":"Patients with chronic migraine and medication overuse headache were treated with CGRP antagonists without drug withdrawal, and efficacy was measured using the MIDAS scale.","limitations":"The study did not include a control group and lacked a drug withdrawal phase, which may affect the generalizability of the results."},{"rthcId":"RPEP-06069","title":"Equine metabolism of the growth hormone secretagogue MK-0677 in vitro and in urine and plasma following oral administration.","authors":"Cutler, Charlotte; Viljanto, Marjaana; Taylor, Polly; Habershon-Butcher, Jocelyn; Van Eenoo, Peter","year":2022,"journal":"Drug testing and analysis, 14(7), 1273-1290","doi":"10.1002/dta.3252","pmid":"35302297","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Fourteen metabolites were identified in vitro; 13 were found in urine and 9 in plasma post-administration.","whyItMatters":"Understanding how MK-0677 is metabolized in horses can help improve doping control measures in equestrian sports. This research is crucial for ensuring fair competition.","specificNumbers":"","methodology":"The study used liquid chromatography high resolution mass spectrometry for metabolite identification and liquid chromatography-tandem mass spectrometry for profiling urine and plasma samples.","limitations":"The study was conducted on a small sample size of only two horses, which may limit the generalizability of the findings."},{"rthcId":"RPEP-06070","title":"The Efficacy and Safety of Abaloparatide-SC in Men With Osteoporosis: A Randomized Clinical Trial.","authors":"Czerwinski, Edward; Cardona, Jose; Plebanski, Rafal; Recknor, Chris; Vokes, Tamara; Saag, Kenneth G; Binkley, Neil; Lewiecki, E Michael; Adachi, Jonathan; Knychas, Dorota; Kendler, David; Orwoll, Eric; Chen, Yinzhong; Pearman, Leny; Li, Y Heather; Mitlak, Bruce","year":2022,"journal":"Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 37(12), 2435-2442","doi":"10.1002/jbmr.4719","pmid":"36190391","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06071","title":"Early life oxytocin treatment improves thermo-sensory reactivity and maternal behavior in neonates lacking the autism-associated gene Magel2.","authors":"Da Prato, Laura Caccialupi; Zayan, Ugo; Abdallah, Dina; Point, Vanessa; Schaller, Fabienne; Pallesi-Pocachard, Emilie; Montheil, Aurélie; Canaan, Stéphane; Gaiarsa, Jean-Luc; Muscatelli, Françoise; Matarazzo, Valéry","year":2022,"journal":"Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 47(11), 1901-1912","doi":"10.1038/s41386-022-01313-5","pmid":"35396500","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Intranasal oxytocin treatment rescued atypical thermosensory responses in Magel2 neonates.","whyItMatters":"Understanding early sensory dysfunctions in autism can lead to potential therapeutic strategies. This research highlights the importance of early intervention in addressing sensory issues.","specificNumbers":"","methodology":"The study involved pharmacogenetic manipulation and intranasal oxytocin administration in neonatal mice models.","limitations":"The study was conducted in mouse models, which may not fully translate to human conditions. Further research is needed to confirm these findings in humans."},{"rthcId":"RPEP-06072","title":"Peptide inhibitors of angiotensin-I converting enzyme based on angiotensin (1-7) with selectivity for the C-terminal domain.","authors":"da Silva, Rogerio L; Papakyriakou, Athanasios; Carmona, Adriana K; Spyroulias, Georgios A; Sturrock, Edward D; Bersanetti, Patrícia A; Nakaie, Clovis R","year":2022,"journal":"Bioorganic chemistry, 129, 106204","doi":"10.1016/j.bioorg.2022.106204","pmid":"36306699","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 15 synthesized derivatives of angiotensin (1-7), Ac-Ang (2-7)-NH2 emerged as the most promising: it is a good ACE inhibitor, resistant to enzymatic cleavage, and shows improved selectivity for the C-terminal domain (cACE) over the N-terminal domain (nACE). Molecular dynamics simulations identified key interactions — Val3 and Tyr4 with ACE subsites, particularly Val3's interaction with the S3 subsite — as critical for the peptide's selectivity. Removing Val3 greatly reduced peptide-enzyme interactions.","whyItMatters":"ACE inhibitors are among the most prescribed drugs worldwide for hypertension and heart disease, but side effects from non-selective inhibition (particularly chronic cough) affect up to 15% of users. Domain-selective ACE inhibitors could maintain blood pressure control while reducing these side effects, improving quality of life for millions of patients.","specificNumbers":"","methodology":"Fifteen peptide derivatives of angiotensin (1-7) were synthesized by systematically removing N-terminal amino acids and modifying peptide ends. Each was tested for ACE inhibition potency and domain selectivity (nACE vs cACE). Resistance to enzymatic cleavage was assessed. Molecular dynamics simulations modeled peptide-enzyme binding to explain selectivity at the molecular level.","limitations":"This is entirely an in vitro and computational study. No animal or human testing was performed. The actual blood pressure-lowering effect and safety of Ac-Ang (2-7)-NH2 in living organisms is unknown. Peptide drugs face significant oral bioavailability challenges that were not addressed. The degree of selectivity improvement was not quantified with specific fold-change values in the abstract."},{"rthcId":"RPEP-06073","title":"Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes: The SURPASS-5 Randomized Clinical Trial.","authors":"Dahl, Dominik; Onishi, Yukiko; Norwood, Paul; Huh, Ruth; Bray, Ross; Patel, Hiren; Rodríguez, Ángel","year":2022,"journal":"JAMA, 327(6), 534-545","doi":"10.1001/jama.2022.0078","pmid":"35133415","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"At week 40, mean HbA1c change was -2.40% with 10 mg tirzepatide vs -0.86% with placebo (P < .001).","whyItMatters":"These results indicate that tirzepatide can be an effective addition to insulin therapy for better blood sugar control in type 2 diabetes. This could lead to improved patient outcomes and management strategies.","specificNumbers":"","methodology":"A randomized phase 3 clinical trial with 475 participants, comparing tirzepatide doses to placebo over 40 weeks.","limitations":"The study was limited to a specific population and duration, and long-term effects of tirzepatide remain to be evaluated."},{"rthcId":"RPEP-06074","title":"Lifetime sexual violence exposure in women compromises systemic innate immune mediators associated with HIV pathogenesis: A cross-sectional analysis.","authors":"Daniels, Jason; Aldous, Annette; Pyra, Maria; Xia, Yu; Juzumaite, Monika; Jais, Mariel; Simmens, Samuel; Murphy, Kerry; Taylor, Tonya N; Kassaye, Seble; Benning, Lorie; Cohen, Mardge H; Weber, Kathleen M; Ghosh, Mimi","year":2022,"journal":"Women's health (London, England), 18, 17455057221099486","doi":"10.1177/17455057221099486","pmid":"35579000","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Abuse + Depression group showed higher MIP-3α and IP-10 levels (p < 0.01) and lower IL-1β (p < 0.01) compared to Control.","whyItMatters":"Understanding how trauma affects immune responses can improve HIV prevention strategies for women. It emphasizes the importance of addressing psychological and physical trauma in healthcare.","specificNumbers":"","methodology":"The study used a cross-sectional analysis of blood samples from 77 women, categorized by HIV status and history of sexual abuse, to measure immune biomarkers.","limitations":"The study's cross-sectional design limits causal inferences, and the sample size may not represent all women with similar experiences."},{"rthcId":"RPEP-06075","title":"The Impact of GLP1 Agonists on Bone Metabolism: A Systematic Review.","authors":"Daniilopoulou, Ioanna; Vlachou, Eugenia; Lambrou, George I; Ntikoudi, Anastasia; Dokoutsidou, Eleni; Fasoi, Georgia; Govina, Ourania; Kavga, Anna; Tsartsalis, Athanasios N","year":2022,"journal":"Medicina (Kaunas, Lithuania), 58(2)","doi":"10.3390/medicina58020224","pmid":"35208548","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06076","title":"β-Defensin: An adroit saviour in teleosts.","authors":"Das, Sweta; Pradhan, Chiranjiv; Pillai, Devika","year":2022,"journal":"Fish & shellfish immunology, 123, 417-430","doi":"10.1016/j.fsi.2022.03.017","pmid":"35331882","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"β-Defensin significantly reduces bacterial colonization and viral copy numbers when overexpressed or knocked down.","whyItMatters":"Understanding β-Defensin's role can lead to better management of fish health and disease prevention strategies in aquaculture.","specificNumbers":"","methodology":"The study involved analyzing the structure, expression, and functions of β-Defensin in fish, focusing on its immune responses.","limitations":"The study primarily focuses on bacterial and viral infections, with limited investigation into parasitic and fungal infections."},{"rthcId":"RPEP-06077","title":"Site-Specific Conjugation Quantitation of a Cysteine-Conjugated Antibody-Drug Conjugate Using Stable Isotope Labeling Peptide Mapping LC-MS/MS Analysis.","authors":"Davis, Tyler K; Jennings, Mark E","year":2022,"journal":"Analytical chemistry, 94(6), 2772-2778","doi":"10.1021/acs.analchem.1c04025","pmid":"35100801","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The new method allows for accurate site-specific quantitation of drug conjugation levels.","whyItMatters":"Understanding drug conjugation sites in ADCs is essential for ensuring their potency and stability, impacting their therapeutic effectiveness.","specificNumbers":"","methodology":"The study employed stable isotope labeling and LC-MS/MS for peptide mapping to analyze ADCs.","limitations":"The study may not address all potential variables affecting ADC performance in vivo."},{"rthcId":"RPEP-06078","title":"Landscaping macrocyclic peptides: stapling hDM2-binding peptides for helicity, protein affinity, proteolytic stability and cell uptake.","authors":"de Araujo, Aline D; Lim, Junxian; Wu, Kai-Chen; Hoang, Huy N; Nguyen, Huy T; Fairlie, David P","year":2022,"journal":"RSC chemical biology, 3(7), 895-904","doi":"10.1039/d1cb00231g","pmid":"35866171","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Rigidifying the macrocycle improved alpha helicity, target affinity, and proteolytic stability.","whyItMatters":"Enhancing the delivery and stability of peptides could lead to more effective cancer therapies. This research provides insights into designing better therapeutic peptides.","specificNumbers":"","methodology":"The study systematically compared various cyclization constraints and linker positions to assess their effects on peptide properties.","limitations":"The study primarily focuses on in vitro conditions, which may not fully replicate in vivo environments."},{"rthcId":"RPEP-06079","title":"LyeTxI-b, a Synthetic Peptide Derived From a Spider Venom, Is Highly Active in Triple-Negative Breast Cancer Cells and Acts Synergistically With Cisplatin.","authors":"de Avelar Júnior, Joaquim Teixeira; Lima-Batista, Edleusa; Castro Junior, Célio José; Pimenta, Adriano Monteiro de Castro; Dos Santos, Raquel Gouvêa; Souza-Fagundes, Elaine Maria; De Lima, Maria Elena","year":2022,"journal":"Frontiers in molecular biosciences, 9, 876833","doi":"10.3389/fmolb.2022.876833","pmid":"35601827","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"LyeTxI-b has a selectivity index 70-fold higher than cisplatin and enhances its effectiveness.","whyItMatters":"Finding new treatments for triple-negative breast cancer is crucial due to the limited options available. LyeTxI-b could lead to more effective and less toxic chemotherapy regimens.","specificNumbers":"","methodology":"The study involved testing LyeTxI-b alone and in combination with cisplatin on triple-negative breast cancer cell lines (MDA-MB-231) to assess cytotoxic effects and mechanisms of cell death.","limitations":"Further studies are needed to fully understand the mechanisms of action and to validate findings in vivo."},{"rthcId":"RPEP-06080","title":"In Silico Prediction of Anti-Infective and Cell-Penetrating Peptides from Thalassophryne nattereri Natterin Toxins.","authors":"De Cena, Gabrielle Lupeti; Scavassa, Bruna Vitória; Conceição, Katia","year":2022,"journal":"Pharmaceuticals (Basel, Switzerland), 15(9)","doi":"10.3390/ph15091141","pmid":"36145362","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Identified 57 bioactive peptides: 19 anti-infective, 8 cell-penetrating, and 30 with both properties.","whyItMatters":"This research could lead to new treatments that address antibiotic resistance and improve drug delivery methods.","specificNumbers":"","methodology":"In silico analysis using various web servers to predict peptide properties and functions.","limitations":"The findings are based on in silico predictions, which may not fully translate to in vivo effectiveness."},{"rthcId":"RPEP-06081","title":"Efficacy and Safety of Semaglutide, a Glucagon-Like Peptide-1 Receptor Agonist in Real-Life: A Case Series of Patients in Maintenance Incremental Hemodialysis.","authors":"De la Flor, José C; Lorenzo, Javier Deira; Marschall, Alexander; Valga, Francisco; Vázquez, Tania Monzón; Cícero, Elisa Ruiz","year":2022,"journal":"Case reports in nephrology and dialysis, 12(3), 238-247","doi":"10.1159/000527919","pmid":"36465574","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide treatment led to a reduction in HbA1c, albuminuria, and weight over 6 months.","whyItMatters":"This research highlights a potential new treatment option for diabetes management in patients with advanced kidney disease, which is often challenging.","specificNumbers":"","methodology":"The study involved a case series of three patients receiving semaglutide while on maintenance incremental hemodialysis, monitored over six months.","limitations":"The study is limited by its small sample size and lack of a control group, which may affect the generalizability of the findings."},{"rthcId":"RPEP-06082","title":"Cranial autonomic symptoms and response to monoclonal antibodies targeting the Calcitonin gene-related peptide pathway: A real-world study.","authors":"De Matteis, Eleonora; Caponnetto, Valeria; Casalena, Alfonsina; Frattale, Ilaria; Gabriele, Amleto; Affaitati, Giannapia; Giamberardino, Maria Adele; Maddestra, Maurizio; Viola, Stefano; Pistoia, Francesca; Sacco, Simona; Ornello, Raffaele","year":2022,"journal":"Frontiers in neurology, 13, 973226","doi":"10.3389/fneur.2022.973226","pmid":"36212640","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Out of 136 patients, 88 (65%) had cranial autonomic symptoms (CAS). During 12 weeks of anti-CGRP treatment, the median reduction in monthly headache days was significantly greater in patients with CAS (-10, IQR -15 to -6) versus without CAS (-6, IQR -12 to -3; p=0.009). However, categorical response rates (30%, 50%, 75%, 100% reduction thresholds) did not differ significantly between groups. The findings suggest CAS may serve as a clinical biomarker of trigeminovascular activation that predicts better response to CGRP-targeting therapies.","whyItMatters":"Predicting which migraine patients will respond best to expensive CGRP-targeting drugs is a major clinical challenge. This study identifies a simple, readily assessable clinical feature — cranial autonomic symptoms — that could help clinicians select the right patients for anti-CGRP treatment. Rather than trying the drug and waiting 12 weeks to assess response, doctors could potentially prioritize patients with CAS as likely strong responders.","specificNumbers":"","methodology":"Prospective real-world study of 136 patients with episodic or chronic migraine treated with anti-CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab) between 2019 and 2021. A 12-week baseline was compared to a 12-week treatment follow-up. CAS prevalence was assessed, and treatment responses were compared between CAS and non-CAS groups using appropriate statistical tests.","limitations":"Relatively small sample size (136 patients) limits statistical power and generalizability. The categorical response rates didn't differ significantly between groups despite the median difference, suggesting the signal may be modest. The study combined three different anti-CGRP antibodies, and differential responses by drug type weren't analyzed. CAS assessment was clinical and may vary between providers. The 12-week follow-up is relatively short for a chronic condition."},{"rthcId":"RPEP-06083","title":"Antitumor and Antiparasitic Activity of Antimicrobial Peptides Derived from Snake Venom: A Systematic Review Approach.","authors":"de Moura, Gabriel Acácio; de Oliveira, Juliana Ramos; Rocha, Yasmim Mendes; de Oliveira Freitas, Janaína; Rodrigues, João Pedro Viana; Ferreira, Vanessa Pinheiro Gonçalves; Nicolete, Roberto","year":2022,"journal":"Current medicinal chemistry, 29(32), 5358-5368","doi":"10.2174/0929867329666220507011719","pmid":"35524668","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"10 peptides showed antiproliferative activity on tumor cells; 7 peptides had antiparasitic activity.","whyItMatters":"With rising drug resistance in pathogens, finding new treatment options is crucial. Snake venom peptides could offer innovative solutions for challenging diseases.","specificNumbers":"","methodology":"The study involved a systematic review of in vitro, in vivo, and in silico studies on snake venom peptides.","limitations":"The study is limited by the small number of articles included and the need for more extensive research to validate findings."},{"rthcId":"RPEP-06084","title":"Antimicrobial-wound healing peptides: Dual-function molecules for the treatment of skin injuries.","authors":"de Souza, Guilherme Sastre; de Jesus Sonego, Leandra; Santos Mundim, Ana Clara; de Miranda Moraes, Júlia; Sales-Campos, Helioswilton; Lorenzón, Esteban Nicolás","year":2022,"journal":"Peptides, 148, 170707","doi":"10.1016/j.peptides.2021.170707","pmid":"34896165","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06085","title":"The incretin/glucagon system as a target for pharmacotherapy of obesity.","authors":"Del Prato, Stefano; Gallwitz, Baptist; Holst, Jens Juul; Meier, Juris J","year":2022,"journal":"Obesity reviews : an official journal of the International Association for the Study of Obesity, 23(2), e13372","doi":"10.1111/obr.13372","pmid":"34713962","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Unimolecular dual and triple agonists targeting combinations of GLP-1, GIP, and glucagon receptors have demonstrated the ability to promote body weight loss, lower glucose levels, and reduce food intake in animal models of obesity. Multiple dual receptor agonists (GLP-1/GIP and GLP-1/glucagon combinations) are now in clinical development for obesity treatment.\n\nThe review highlights that glucagon may contribute to weight loss by reducing food intake, while simultaneous GLP-1 receptor activation helps maintain normal blood sugar control — addressing a key concern about using glucagon-based therapies in people with metabolic disorders.","whyItMatters":"Current obesity medications have limited effectiveness because they typically target only one metabolic pathway. This review makes the case that combining multiple peptide hormone targets into a single drug could be far more effective. This multi-targeting approach has already led to breakthrough drugs like tirzepatide, and understanding the science behind these combinations is key to developing the next generation of obesity treatments.","specificNumbers":"","methodology":"This is a narrative review that synthesizes published research on proglucagon-derived peptides and their role in obesity management. The authors evaluated preclinical animal studies and early clinical development data on dual and triple receptor agonists targeting the incretin and glucagon hormone systems.","limitations":"Most evidence for dual and triple agonists at the time of this review came from animal models, which don't always predict human outcomes. The exact contribution of glucagon receptor activation to weight loss versus potential adverse metabolic effects was not fully understood. The review also acknowledges that the molecular mechanisms of action for these multi-target drugs require further elucidation."},{"rthcId":"RPEP-06086","title":"Strategies for improving antimicrobial peptide production.","authors":"Deo, Soumya; Turton, Kristi L; Kainth, Tajinder; Kumar, Ayush; Wieden, Hans-Joachim","year":2022,"journal":"Biotechnology advances, 59, 107968","doi":"10.1016/j.biotechadv.2022.107968","pmid":"35489657","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies ongoing challenges in AMP production, including low yield and degradation.","whyItMatters":"With antibiotic resistance on the rise, enhancing AMP production could provide new therapeutic options. Understanding and improving AMP production methods is vital for their clinical application.","specificNumbers":"","methodology":"The study is a review of existing literature on antimicrobial peptide production strategies and expression systems.","limitations":"The review does not provide new experimental data but summarizes existing literature, which may not capture the latest developments."},{"rthcId":"RPEP-06087","title":"A Combination of Native LC-MS Approaches for the Comprehensive Characterization of the Antibody-Drug Conjugate Trastuzumab Deruxtecan.","authors":"Deslignière, Evolène; Diemer, Hélène; Erb, Stéphane; Coliat, Pierre; Pivot, Xavier; Detappe, Alexandre; Hernandez-Alba, Oscar; Cianférani, Sarah","year":2022,"journal":"Frontiers in bioscience (Landmark edition), 27(10), 290","doi":"10.31083/j.fbl2710290","pmid":"36336868","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The average drug-to-antibody ratio (DAR) of T-DXd was found to be 8.","whyItMatters":"Understanding the detailed structure of antibody-drug conjugates can enhance their effectiveness and safety. These methods may streamline the development of biopharmaceuticals.","specificNumbers":"","methodology":"The study utilized native mass spectrometry combined with size exclusion, cation exchange, and hydrophobic interaction chromatography to analyze T-DXd.","limitations":"The study faced challenges in identifying minor variants due to poor mass spectrometry signal quality."},{"rthcId":"RPEP-06088","title":"Peptide-based hydrogels as delivery systems for doxorubicin.","authors":"Diaferia, Carlo; Rosa, Elisabetta; Accardo, Antonella; Morelli, Giancarlo","year":2022,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 28(1), e3301","doi":"10.1002/psc.3301","pmid":"33491262","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06089","title":"Research on ACEI of Low-Molecular-Weight Peptides from Hirudo nipponia Whitman.","authors":"Ding, Zhao; Chen, Keli; Chen, Yunzhong","year":2022,"journal":"Molecules (Basel, Switzerland), 27(17)","doi":"10.3390/molecules27175421","pmid":"36080189","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Four peptide fractions showed ACE inhibitory activity with IC50 values of 0.8266, 0.2708, 0.4432, and 0.1764 mg/mL.","whyItMatters":"Understanding the ACE inhibitory activity of these peptides could lead to new treatments for hypertension. This research expands knowledge on natural compounds that can influence blood pressure.","specificNumbers":"","methodology":"The study used prep-HPLC to separate peptides from Hirudo nipponia, followed by Orbitrap LC-MS analysis and bioassays to determine ACE inhibitory activity.","limitations":"The study is limited to in vitro findings, and further research is needed to confirm effects in vivo and in humans."},{"rthcId":"RPEP-06090","title":"Antimicrobial and Anti-inflammatory Gallium-Defensin Surface Coatings for Implantable Devices.","authors":"Divakarla, Shiva Kamini; Das, Theerthankar; Chatterjee, Chandralekha; Ionescu, Mihail; Pastuovic, Zeljko; Jang, Jun-Hyeog; Al-Khoury, Hala; Loppnow, Harald; Yamaguchi, Seiji; Groth, Thomas; Chrzanowski, Wojciech","year":2022,"journal":"ACS applied materials & interfaces, 14(7), 9685-9696","doi":"10.1021/acsami.1c19579","pmid":"35133137","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Polylactic acid films were modified with gallium ion implantation and functionalized with human beta-defensin-1 (hBD-1). Both components independently and synergistically reduced total live bacterial biomass on the surfaces.\n\nA key novel finding was that defensin's antimicrobial activity was \"unlocked\" by surface immobilization — its in vitro effectiveness had previously been disappointing compared to its in vivo performance. Gallium implantation also reduced foreign body giant cell formation and IL-1β proinflammatory cytokine expression. The combined surfaces killed bacteria and reduced inflammation without inducing cellular toxicity.","whyItMatters":"Implant infections are a major clinical problem, often requiring device removal and additional surgery. Current approaches rely heavily on antibiotics, which contribute to resistance. A peptide-based coating that harnesses the body's own immune defense molecules while also reducing inflammation could be a game-changer for implant safety.","specificNumbers":"","methodology":"Researchers fabricated polylactic acid films, modified them with gallium ion implantation, and then functionalized the surfaces with defensin peptide. They characterized surface properties (roughness, stiffness) and tested antimicrobial activity against bacterial biofilms and anti-inflammatory effects by measuring immune cell responses and cytokine levels in vitro.","limitations":"This was entirely an in vitro study — the coatings have not been tested in animals or humans. Long-term durability of the coating, the defensin's stability over time, and performance in the complex in vivo environment remain unknown. Only one bacterial species and one defensin variant were tested."},{"rthcId":"RPEP-06091","title":"Effects of Dapagliflozin in Asian Patients With Heart Failure and Reduced Ejection Fraction in DAPA-HF.","authors":"Docherty, Kieran F; Anand, Inder S; Chiang, Chern-En; Chopra, Vijay K; Desai, Akshay S; Kitakaze, Masafumi; Verma, Subodh; Vinh, Pham N; Inzucchi, Silvio E; Køber, Lars; Kosiborod, Mikhail N; Martinez, Felipe A; Bengtsson, Olof; Ponikowski, Piotr; Sabatine, Marc S; Sjöstrand, Mikaela; Solomon, Scott D; Langkilde, Anna Maria; Jhund, Pardeep S; McMurray, John J V","year":2022,"journal":"JACC. Asia, 2(2), 139-153","doi":"10.1016/j.jacasi.2022.02.004","pmid":"36339117","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Dapagliflozin reduced the risk of worsening heart failure events and cardiovascular death in Asian patients (HR: 0.65) similarly to patients elsewhere (HR: 0.77).","whyItMatters":"Understanding the effects of dapagliflozin in diverse populations can improve treatment strategies for heart failure. This research highlights that the medication is equally effective in Asian patients.","specificNumbers":"","methodology":"The study analyzed data from the DAPA-HF trial, focusing on Asian patients with heart failure and comparing their outcomes to those from other regions.","limitations":"The study may not account for all regional variations in heart failure treatment and outcomes, and results from clinical trials may not fully translate to real-world settings."},{"rthcId":"RPEP-06092","title":"Keratinocyte-derived defensins activate neutrophil-specific receptors Mrgpra2a/b to prevent skin dysbiosis and bacterial infection.","authors":"Dong, Xintong; Limjunyawong, Nathachit; Sypek, Elizabeth I; Wang, Gaofeng; Ortines, Roger V; Youn, Christine; Alphonse, Martin P; Dikeman, Dustin; Wang, Yu; Lay, Mark; Kothari, Ruchita; Vasavda, Chirag; Pundir, Priyanka; Goff, Loyal; Miller, Lloyd S; Lu, Wuyuan; Garza, Luis A; Kim, Brian S; Archer, Nathan K; Dong, Xinzhong","year":2022,"journal":"Immunity, 55(9), 1645-1662.e7","doi":"10.1016/j.immuni.2022.06.021","pmid":"35882236","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The study identified Mrgpra2a/b — previously orphan G-protein-coupled receptors on neutrophils — as the receptors for keratinocyte-derived defensins. This represents a novel epithelial-to-immune cell signaling axis.\n\nMice lacking either the entire defensin gene cluster in keratinocytes or the Mrgpra2a/b receptors developed skin dysbiosis characterized by reduced microbial diversity and expansion of Staphylococcus species. Both mutant lines showed impaired neutrophil abscess formation — a hallmark of antibacterial immunity — and increased susceptibility to S. aureus skin infections. Mechanistically, defensin activation of Mrgpra2 triggered neutrophil release of IL-1β and CXCL2, which are critical for amplifying and propagating the antibacterial immune response.","whyItMatters":"This study redefines defensins from simple antimicrobial agents to immune signaling molecules. By revealing how skin epithelial cells communicate with neutrophils through defensins, it opens new therapeutic avenues — boosting this pathway could help treat skin infections (especially antibiotic-resistant Staph), while understanding its disruption could explain conditions like eczema where the skin microbiome is disturbed.","specificNumbers":"","methodology":"The researchers generated two mutant mouse lines: one lacking the entire defensin gene cluster specifically in keratinocytes, and another lacking the Mrgpra2a/b receptors. They assessed skin microbiome composition, challenged mice with S. aureus skin infections, analyzed neutrophil abscess formation, and measured cytokine/chemokine release (IL-1β, CXCL2) upon defensin-Mrgpra2 activation.","limitations":"The study was conducted entirely in mice, and the human orthologs of Mrgpra2a/b (MRGPRX2) have somewhat different expression patterns and functions. The specific defensins responsible for Mrgpra2 activation in vivo were not individually identified. Whether this axis operates similarly in other tissues beyond skin was not explored."},{"rthcId":"RPEP-06093","title":"Sodium butyrate alleviates LPS-induced kidney injury via inhibiting TLR2/4 to regulate rBD2 expression.","authors":"Dou, Xiujing; Yan, Di; Ma, Ziwen; Gao, Nan; Shan, Anshan","year":2022,"journal":"Journal of food biochemistry, 46(7), e14126","doi":"10.1111/jfbc.14126","pmid":"35322444","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"NaB reduced kidney damage indicators like creatinine and TNF-α levels.","whyItMatters":"This research highlights a potential dietary approach to enhance kidney health and reduce inflammation, which could have implications for animal husbandry and human health.","specificNumbers":"","methodology":"The study used a rat model to assess the effects of sodium butyrate on LPS-induced kidney injury.","limitations":"The study was conducted in rats, so results may not directly translate to humans."},{"rthcId":"RPEP-06094","title":"Metabolic remodeling of glycerophospholipids acts as a signature of dulaglutide and liraglutide treatment in recent-onset type 2 diabetes mellitus.","authors":"Du, Juan; Xi, Liuqing; Zhang, Zhongxiao; Ge, Xiaoxu; Li, Wenyi; Peng, Wenfang; Jiang, Xiaohong; Liu, Wen; Zhao, Nan; Wang, Xingyun; Guo, Xirong; Huang, Shan","year":2022,"journal":"Frontiers in endocrinology, 13, 1097612","doi":"10.3389/fendo.2022.1097612","pmid":"36686441","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"46 and 45 differentially regulated metabolites were identified after dulaglutide and liraglutide treatments, respectively.","whyItMatters":"Understanding how these medications remodel lipid metabolism can help improve diabetes treatment strategies and patient outcomes.","specificNumbers":"","methodology":"The study involved 52 type 2 diabetes patients and 28 controls, using untargeted metabolomics analysis to track serum metabolic changes over 12 weeks.","limitations":"The study's sample size is relatively small, and results may not fully translate to broader populations."},{"rthcId":"RPEP-06095","title":"The recombinant defensin/HSA fusion protein that inhibits NF-κb associated with intensive macropinocytosis shows potent efficacy against pancreatic cancer.","authors":"Du, Yi-Bo; Wang, Xiao-Fei; Liu, Xiu-Jun; Li, Yi; Miao, Qing-Fang; Jiang, Min; Sheng, Wei-Jin; Zhen, Yong-Su","year":2022,"journal":"Biochemical pharmacology, 201, 115057","doi":"10.1016/j.bcp.2022.115057","pmid":"35489393","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"DF2-HSA inhibited tumor growth in mice and showed over 14 days of retention at the tumor site.","whyItMatters":"This research could lead to more effective treatments for pancreatic cancer, a disease known for its poor prognosis. Targeting both NF-κB and KRAS mutations may improve therapeutic outcomes.","specificNumbers":"","methodology":"The study involved creating a recombinant protein, testing its effects on pancreatic cancer cell lines, and conducting in vivo experiments in mice.","limitations":"The study was conducted in vitro and in mice, so results may not fully translate to human patients. Further clinical trials are necessary."},{"rthcId":"RPEP-06096","title":"Utility of Downstream Biomarkers to Assess and Optimize Intranasal Delivery of Oxytocin.","authors":"DuBois, Megan; Tseng, Angela; Francis, Sunday M; Haynos, Ann F; Peterson, Carol B; Jacob, Suma","year":2022,"journal":"Pharmaceutics, 14(6)","doi":"10.3390/pharmaceutics14061178","pmid":"35745751","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Urinary oxytocin levels were significantly higher after intranasal delivery of oxytocin compared to placebo.","whyItMatters":"Understanding how oxytocin is absorbed and cleared can help improve its use in treating conditions like autism and anorexia. This research may lead to better dosing strategies for therapeutic interventions.","specificNumbers":"","methodology":"The study used a double-blind, placebo-controlled crossover design with 40 IU of intranasal oxytocin administered to participants.","limitations":"The study's sample size was relatively small, and results may not fully translate to broader populations."},{"rthcId":"RPEP-06097","title":"Zn(II) binding to pramlintide results in a structural kink, fibril formation and antifungal activity.","authors":"Dudek, Dorota; Dzień, Emilia; Wątły, Joanna; Matera-Witkiewicz, Agnieszka; Mikołajczyk, Aleksandra; Hajda, Agata; Olesiak-Bańska, Joanna; Rowińska-Żyrek, Magdalena","year":2022,"journal":"Scientific reports, 12(1), 20543","doi":"10.1038/s41598-022-24968-y","pmid":"36446825","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Zinc binding induces a structural kink in pramlintide, leading to fibril formation and antifungal activity.","whyItMatters":"Understanding the antifungal properties of pramlintide could lead to new therapeutic applications for this peptide. It also opens up avenues for exploring metal-peptide interactions in drug development.","specificNumbers":"","methodology":"The study utilized bioinorganic chemistry techniques to analyze the interaction between zinc and pramlintide.","limitations":"The study primarily focuses on in vitro findings, which may not directly translate to in vivo efficacy in humans."},{"rthcId":"RPEP-06098","title":"G Protein-Coupled Receptors as Potential Intercellular Communication Mediators in Trypanosomatidae.","authors":"Díaz, Emilia; Febres, Anthony; Giammarresi, Michelle; Silva, Adrian; Vanegas, Oriana; Gomes, Carlos; Ponte-Sucre, Alicia","year":2022,"journal":"Frontiers in cellular and infection microbiology, 12, 812848","doi":"10.3389/fcimb.2022.812848","pmid":"35651757","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Neuropeptides like Substance P stimulate Leishmania movement, indicating GPCR involvement.","whyItMatters":"Understanding how parasites communicate can lead to new strategies for treating infections. Targeting these signaling pathways may provide novel therapeutic options against Leishmania.","specificNumbers":"","methodology":"The study involved in vitro experiments to assess the effects of neuropeptides on Leishmania movement and signaling pathways.","limitations":"The study primarily focuses on in vitro findings, which may not fully translate to in vivo conditions."},{"rthcId":"RPEP-06099","title":"SP/NK1R system regulates carcinogenesis in prostate cancer: Shedding light on the antitumoral function of aprepitant.","authors":"Ebrahimi, Safieh; Mirzavi, Farshad; Aghaee-Bakhtiari, Seyed Hamid; Hashemy, Seyed Isaac","year":2022,"journal":"Biochimica et biophysica acta. Molecular cell research, 1869(5), 119221","doi":"10.1016/j.bbamcr.2022.119221","pmid":"35134443","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Aprepitant significantly increased survival time in mice with prostate cancer compared to untreated groups.","whyItMatters":"Understanding the SP/NK1R system's role in prostate cancer could lead to new treatment strategies. Aprepitant's potential as a therapeutic agent may improve patient outcomes.","specificNumbers":"","methodology":"The study used various assays to measure cell proliferation, migration, and protein expression, alongside in vivo experiments in a mouse model.","limitations":"The study primarily focused on in vitro and mouse models, which may not fully represent human responses."},{"rthcId":"RPEP-06100","title":"The redox modulatory effects of SP/NK1R system: Implications for oxidative stress-associated disorders.","authors":"Ebrahimi, Safieh; Alalikhan, Abbas; Aghaee-Bakhtiari, Seyed Hamid; Hashemy, Seyed Isaac","year":2022,"journal":"Life sciences, 296, 120448","doi":"10.1016/j.lfs.2022.120448","pmid":"35247438","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The SP/NK1R system can influence oxidative stress in a context-dependent manner.","whyItMatters":"Understanding the role of the SP/NK1R system in oxidative stress could lead to new therapeutic strategies for managing related diseases.","specificNumbers":"","methodology":"The authors conducted a comprehensive literature review using PubMed/Medline and Scopus databases.","limitations":"The study is primarily a literature review and does not present original experimental data."},{"rthcId":"RPEP-06101","title":"Seaweed-Derived Proteins and Peptides: Promising Marine Bioactives.","authors":"Echave, Javier; Otero, Paz; Garcia-Oliveira, Paula; Munekata, Paulo E S; Pateiro, Mirian; Lorenzo, Jose M; Simal-Gandara, Jesus; Prieto, Miguel A","year":2022,"journal":"Antioxidants (Basel, Switzerland), 11(1)","doi":"10.3390/antiox11010176","pmid":"35052680","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06102","title":"Antimicrobial peptides from freshwater invertebrate species: potential for future applications.","authors":"Egessa, Robert","year":2022,"journal":"Molecular biology reports, 49(10), 9797-9811","doi":"10.1007/s11033-022-07483-1","pmid":"35716292","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Freshwater invertebrates contain diverse antimicrobial peptides effective against bacteria, fungi, and viruses.","whyItMatters":"Understanding these peptides can lead to new antimicrobial agents for various industries, addressing antibiotic resistance and enhancing food safety.","specificNumbers":"","methodology":"This is a review study summarizing findings from various investigations over recent decades.","limitations":"As a review, it summarizes existing studies without original experimental data, limiting direct conclusions."},{"rthcId":"RPEP-06103","title":"Adenovirus-α-Defensin Complexes Induce NLRP3-Associated Maturation of Human Phagocytes via Toll-Like Receptor 4 Engagement.","authors":"Eichholz, Karsten; Tran, Tuan Hiep; Chéneau, Coraline; Tran, Thi Thu Phuong; Paris, Océane; Pugniere, Martine; Kremer, Eric J","year":2022,"journal":"Journal of virology, 96(6), e0185021","doi":"10.1128/jvi.01850-21","pmid":"35080426","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"HNP-1 (human neutrophil protein 1), an alpha-defensin antimicrobial peptide, binds directly to the capsids of three different human adenovirus types (HAdV-C5, -D26, and -B35). This binding redirects the viruses to Toll-like receptor 4 (TLR4) on human phagocytes, leading to internalization of the virus-defensin complex.\n\nThe TLR4 engagement triggers an NLRP3 inflammasome response, resulting in the release of interleukin-1 beta (IL-1β) — a key inflammatory cytokine that activates broader immune responses. Notably, this IL-1β release occurred without significant disruption of the cell's plasma membrane, indicating a non-destructive, controlled activation pathway rather than cell death-associated inflammation.","whyItMatters":"Adenovirus-based vaccines — including some COVID-19 vaccines — are widely used, but how the body's own antimicrobial peptides interact with these vaccines at the injection site has been poorly understood. This study reveals that alpha-defensins released by neutrophils don't just fight infection — they actively shape the immune response to vaccines by creating virus-peptide complexes that trigger specific inflammatory pathways. This mechanism could be harnessed to design more effective vaccines.","specificNumbers":"","methodology":"The researchers conducted in vitro experiments using human phagocytes exposed to complexes of HNP-1 and three human adenovirus types. They measured HNP-1 binding to viral capsids, tracked receptor engagement using TLR4 pathway analysis, assessed inflammasome activation via NLRP3, and quantified IL-1β release. Plasma membrane integrity was monitored to determine whether the inflammatory response involved cell damage.","limitations":"All experiments were conducted in vitro using isolated human phagocytes, which may not fully replicate the complex tissue environment at a vaccine injection site. The study did not measure downstream adaptive immune responses (antibody or T-cell responses) that would confirm enhanced vaccine efficacy. The concentrations of HNP-1 used may differ from physiological levels at injection sites. Only three adenovirus types were tested."},{"rthcId":"RPEP-06104","title":"Reno-protective effects of GLP-1 receptor agonist and anti-platelets in experimentally induced diabetic kidney disease in male albino rats.","authors":"El Amin Ali, Amani M; Osman, Hamed M; Zaki, Azaa M; Shaker, Olfat; Elsayed, Asma Mohammed; Abdelwahed, Mostafa Yehia; Mohammed, Rahab Ahmed","year":2022,"journal":"Iranian journal of basic medical sciences, 25(12), 1487-1497","doi":"10.22038/IJBMS.2022.65061.14494","pmid":"36544522","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 60 diabetic rats, both dulaglutide and metformin significantly decreased blood pressure, blood glucose, serum lipids, and improved kidney functional parameters compared to untreated diabetic controls. These improvements were associated with increased antioxidant markers, decreased inflammatory markers (NF-κB gene expression), and reduced fibrotic changes in kidney tissue.\n\nAdding cilostazol to either dulaglutide or metformin further enhanced some antioxidant and anti-inflammatory properties. Histopathological examination confirmed that treated groups had improved kidney tissue architecture compared to untreated diabetic rats. Dulaglutide also increased eNOS gene expression in kidney tissue, suggesting improved vascular function.","whyItMatters":"Diabetic kidney disease affects about 40% of diabetes patients and is the leading cause of end-stage renal disease. GLP-1 drugs like dulaglutide are already showing kidney-protective effects in human trials, and this study helps explain why — through antioxidant, anti-inflammatory, and anti-fibrotic mechanisms. The potential synergy with cilostazol could offer an enhanced combination strategy for kidney protection in diabetic patients.","specificNumbers":"","methodology":"Sixty male albino rats with induced type 2 diabetes were randomly divided into 5 groups: untreated diabetic controls, and four treatment groups receiving metformin, dulaglutide, metformin + cilostazol, or dulaglutide + cilostazol. After the treatment period, researchers measured body weight, blood pressure, fasting blood glucose, lipid profiles, and kidney function markers. Kidney tissue was analyzed for eNOS and NF-κB gene expression and examined histopathologically.","limitations":"This is a rat model of induced diabetes, which may not perfectly replicate human diabetic kidney disease. The study did not report specific numerical values for kidney function markers in the abstract. The duration of treatment was not specified. Cilostazol's additive benefits appeared to be partial rather than dramatic. The mechanism linking cilostazol's anti-platelet effects to improved kidney antioxidant properties needs further investigation."},{"rthcId":"RPEP-06105","title":"Hypertension Related to Obesity: Pathogenesis, Characteristics and Factors for Control.","authors":"El Meouchy, Paul; Wahoud, Mohamad; Allam, Sabine; Chedid, Roy; Karam, Wissam; Karam, Sabine","year":2022,"journal":"International journal of molecular sciences, 23(20)","doi":"10.3390/ijms232012305","pmid":"36293177","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Obesity increases the risk of hypertension through mechanisms like insulin resistance and oxidative stress.","whyItMatters":"Understanding the link between obesity and hypertension is crucial for developing effective treatments and prevention strategies. This knowledge can help healthcare providers better manage patients at risk.","specificNumbers":"","methodology":"The study reviews existing literature on the relationship between obesity and hypertension, examining various contributing factors.","limitations":"The study primarily reviews existing literature and does not present new experimental data."},{"rthcId":"RPEP-06106","title":"Synthesis and Evaluation of High Functionality and Quality Cell-penetrating Peptide Conjugated Lipid for Octaarginine Modified PEGylated Liposomes In U251 and U87 Glioma Cells.","authors":"El-Gamal, Farid R; Akl, Mohamed A; Mowafy, Hammam A; Mukai, Hidefumi; Kawakami, Shigeru; Afouna, Mohsen I","year":2022,"journal":"Journal of pharmaceutical sciences, 111(6), 1719-1727","doi":"10.1016/j.xphs.2021.11.022","pmid":"34863974","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The new liposomes exhibited a cellular association of ∼15.87-fold, compared to 10.4-fold for conventional liposomes.","whyItMatters":"Improving drug delivery to glioma cells could lead to more effective treatments for brain tumors. This research offers a promising alternative to existing liposome designs.","specificNumbers":"","methodology":"The study involved synthesizing and characterizing new liposomes, followed by in vitro testing on glioma cell lines U251 and U87.","limitations":"The study was conducted in vitro, and results may not directly translate to in vivo conditions or human patients."},{"rthcId":"RPEP-06107","title":"The antimicrobial peptide alpha defensin correlates to type 2 diabetes via the advanced glycation end products pathway.","authors":"El-Mowafy, Mohammed; Elgaml, Abdelaziz; Abass, Naglaa; Mousa, Amany A; Amin, Mohamed N","year":2022,"journal":"African health sciences, 22(1), 303-311","doi":"10.4314/ahs.v22i1.37","pmid":"36032426","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Serum alpha-defensin levels were significantly elevated in type 2 diabetes patients both with diabetic neuropathy (n=47) and without complications (n=19) compared to healthy controls (n=19).\n\nAlpha-defensin levels showed significant positive correlations with advanced glycation end products (AGEs), fasting blood glucose, and body mass index. The correlation with AGEs is particularly notable, as it suggests a crosstalk between innate immune antimicrobial peptides and the glycation pathway that may amplify chronic inflammation in diabetes.","whyItMatters":"Chronic low-grade inflammation is a hallmark of type 2 diabetes that contributes to complications like neuropathy, cardiovascular disease, and kidney damage. Finding that the antimicrobial peptide alpha-defensin is elevated and correlates with AGEs identifies a previously underappreciated link between innate immunity and diabetic inflammation. This could point to new biomarkers or therapeutic targets for managing diabetic complications.","specificNumbers":"","methodology":"Cross-sectional study comparing three groups: 47 type 2 diabetes patients with diabetic neuropathy, 19 type 2 diabetes patients without complications, and 19 healthy controls. Serum alpha-defensin was measured by ELISA. Additional measurements included AGEs, fasting blood glucose, and lipid profiles.","limitations":"The sample size is small (85 total participants), limiting statistical power and generalizability. The cross-sectional design cannot establish whether elevated alpha-defensin causes or results from diabetic inflammation. The study was conducted at a single center. Specific alpha-defensin subtypes were not differentiated. Confounders like medication use, infection status, and diabetes duration were not fully addressed in the abstract."},{"rthcId":"RPEP-06108","title":"Dapagliflozin, Liraglutide, and Their Combination Attenuate Diabetes Mellitus-Associated Hepato-Renal Injury-Insight into Oxidative Injury/Inflammation/Apoptosis Modulation.","authors":"El-Sherbiny, Mohamed; El-Shafey, Mohamed; Said, Eman; Shaker, Gehan Ahmed; El-Dosoky, Mohamed; Ebrahim, Hasnaa Ali; Abed, Sally Yussef; Ibraheem, Khalid M; Mohsen Faheem, Ahmed; AlMutawa, Muntazar; Alatawi, Bayader; Elsherbiny, Nehal M","year":2022,"journal":"Life (Basel, Switzerland), 12(5)","doi":"10.3390/life12050764","pmid":"35629430","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Combined treatment with dapagliflozin and liraglutide significantly reduced liver and kidney injury markers compared to either drug alone.","whyItMatters":"This research highlights a promising combination therapy for preventing serious complications in diabetes patients, potentially improving their quality of life.","specificNumbers":"","methodology":"The study involved biochemical assessments and histopathological examinations to evaluate the effects of the drugs on diabetic complications.","limitations":"The study does not include human trials, so results may not directly translate to clinical practice."},{"rthcId":"RPEP-06109","title":"Impact of biliopancreatic diversion with duodenal switch on glucose homeostasis and gut hormones and their correlations with appetite.","authors":"Elias, Khalid; Webb, Dominic-Luc; Diaz Tartera, Hetzel O; Hellström, Per M; Sundbom, Magnus","year":2022,"journal":"Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery, 18(12), 1392-1398","doi":"10.1016/j.soard.2022.08.010","pmid":"36151028","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BPD/DS resulted in a 66.1% excess BMI loss, reduced leptin, and increased GLP-1 and PYY.","whyItMatters":"Understanding how BPD/DS affects gut hormones can help improve weight loss strategies and appetite management for patients undergoing this surgery.","specificNumbers":"","methodology":"The study involved 28 patients who were assessed preoperatively and 19 postoperatively, measuring hormone levels and appetite responses after a mixed meal.","limitations":"The study had a small sample size and only included patients from a single hospital, which may limit the generalizability of the findings."},{"rthcId":"RPEP-06110","title":"Significance of Mast Cell Formed Extracellular Traps in Microbial Defense.","authors":"Elieh Ali Komi, Daniel; Kuebler, Wolfgang M","year":2022,"journal":"Clinical reviews in allergy & immunology, 62(1), 160-179","doi":"10.1007/s12016-021-08861-6","pmid":"34024033","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Mast cells can eliminate pathogens through extracellular traps, with the type of stimulus affecting cell survival.","whyItMatters":"This research enhances our understanding of immune responses and could inform treatments for infections and inflammatory diseases.","specificNumbers":"","methodology":"The study reviews existing literature and techniques used to investigate the biology of mast cell extracellular traps.","limitations":"The review is based on existing studies and may not include all recent findings or experimental data."},{"rthcId":"RPEP-06111","title":"Direct contact-mediated non-viral gene therapy using thermo-sensitive hydrogel-coated dressings.","authors":"Eltaher, Hoda M; Blokpoel Ferreras, Lia A; Jalal, Aveen R; Dixon, James E","year":2022,"journal":"Biomaterials advances, 143, 213177","doi":"10.1016/j.bioadv.2022.213177","pmid":"36371970","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Localized gene transfer was achieved in vitro using hydrogel-coated nanoparticles.","whyItMatters":"This research could lead to more effective gene therapies by allowing precise targeting of treatments, potentially improving patient outcomes in regenerative medicine.","specificNumbers":"","methodology":"The study involved optimizing a thermo-reversible hydrogel system for gene delivery and testing its effectiveness in vitro.","limitations":"The study was conducted in vitro, and further research is needed to confirm efficacy in vivo."},{"rthcId":"RPEP-06112","title":"Subcutaneous catabolism of peptide therapeutics: bioanalytical approaches and ADME considerations.","authors":"Esposito, Simone; Orsatti, Laura; Pucci, Vincenzo","year":2022,"journal":"Xenobiotica; the fate of foreign compounds in biological systems, 52(8), 828-839","doi":"10.1080/00498254.2022.2119180","pmid":"36039395","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06113","title":"Antiviral peptides against SARS-CoV-2: therapeutic targets, mechanistic antiviral activity, and efficient delivery.","authors":"Essa, Raahilah Zahir; Wu, Yuan-Seng; Batumalaie, Kalaivani; Sekar, Mahendran; Poh, Chit-Laa","year":2022,"journal":"Pharmacological reports : PR, 74(6), 1166-1181","doi":"10.1007/s43440-022-00432-6","pmid":"36401119","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06114","title":"Epigenetic potentiation of somatostatin-2 by guadecitabine in neuroendocrine neoplasias as a novel method to allow delivery of peptide receptor radiotherapy.","authors":"Evans, Joanne S; Beaumont, Jamie; Braga, Marta; Masrour, Nahal; Mauri, Francesco; Beckley, Alice; Butt, Shamus; Karali, Christina S; Cawthorne, Chris; Archibald, Stephen; Aboagye, Eric O; Sharma, Rohini","year":2022,"journal":"European journal of cancer (Oxford, England : 1990), 176, 110-120","doi":"10.1016/j.ejca.2022.09.009","pmid":"36208569","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Guadecitabine treatment resulted in a 150% increase in SSTR2 uptake in BON-1 models.","whyItMatters":"Enhancing SSTR2 expression could expand treatment options for patients with neuroendocrine neoplasias who currently lack effective therapies. This research opens the door for improved outcomes in peptide receptor radionuclide therapy.","specificNumbers":"","methodology":"The study involved in vitro and in vivo experiments using neuroendocrine neoplasia models, methylation profiling of clinical samples, and safety assessments for combined treatment.","limitations":"The study primarily focused on specific cell lines and may not fully represent all neuroendocrine neoplasias in patients."},{"rthcId":"RPEP-06115","title":"Synergistic Activity of the Human Lactoferricin-Derived Peptide hLF1-11 in Combination with Caspofungin against Candida Species.","authors":"Fais, Roberta; Rizzato, Cosmeri; Franconi, Iacopo; Tavanti, Arianna; Lupetti, Antonella","year":2022,"journal":"Microbiology spectrum, 10(4), e0124022","doi":"10.1128/spectrum.01240-22","pmid":"35876581","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The combination of hLF1-11 and caspofungin showed a fractional inhibitory concentration (FIC) range of 0.28 to 0.37, indicating strong synergy.","whyItMatters":"This research highlights a potential new treatment strategy for infections caused by drug-resistant Candida species, which are a significant threat to immunocompromised patients.","specificNumbers":"","methodology":"The study used checkerboard assays to evaluate synergy, measuring metabolic activity against planktonic and biofilm-forming Candida cells.","limitations":"The study was conducted in vitro, so results may not directly translate to clinical settings."},{"rthcId":"RPEP-06116","title":"Unexpected role for IGF-1 in starvation: Maintenance of blood glucose.","authors":"Fang, Fei; Goldstein, Joseph L; Shi, Xuanming; Liang, Guosheng; Brown, Michael S","year":2022,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 119(32), e2208855119","doi":"10.1073/pnas.2208855119","pmid":"35914126","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Starved ghrelin-deficient mice had a 90% reduction in plasma IGF-1 compared to wild-type mice.","whyItMatters":"Understanding how IGF-1 functions during starvation could inform treatments for metabolic disorders and improve our knowledge of energy regulation.","specificNumbers":"","methodology":"The study involved comparing wild-type mice and ghrelin-deficient mice under starvation conditions, measuring plasma IGF-1 levels and glucose production.","limitations":"The study was conducted in mice, and results may not directly translate to humans."},{"rthcId":"RPEP-06117","title":"In-silico analysis of non-synonymous single nucleotide polymorphisms in human β-defensin type 1 gene reveals their impact on protein-ligand binding sites.","authors":"Fareed, Muhammad Mazhar; Ullah, Sana; Aziz, Shan; Johnsen, Todd Axel; Shityakov, Sergey","year":2022,"journal":"Computational biology and chemistry, 98, 107669","doi":"10.1016/j.compbiolchem.2022.107669","pmid":"35452998","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Four significant nsSNPs were identified, with two affecting PIP2 binding.","whyItMatters":"Understanding these genetic variations can help in assessing risks for diseases and developing targeted therapies. It sheds light on how immune proteins function and their role in health.","specificNumbers":"","methodology":"The study utilized computational algorithms to analyze SNPs and performed molecular docking and dynamics simulations.","limitations":"The study is based on computational analysis, which may not fully capture biological complexities in living organisms."},{"rthcId":"RPEP-06118","title":"Advancement of cell-penetrating peptides in combating triple-negative breast cancer.","authors":"Fatima, Mahak; Abourehab, Mohammed A S; Aggarwal, Geeta; Jain, Gaurav K; Sahebkar, Amirhossein; Kesharwani, Prashant","year":2022,"journal":"Drug discovery today, 27(11), 103353","doi":"10.1016/j.drudis.2022.103353","pmid":"36099963","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CPPs are effective in delivering chemotherapeutics and siRNA into tumor cells.","whyItMatters":"Understanding how CPPs can enhance drug delivery could lead to more effective cancer therapies. This is particularly important for aggressive cancers like triple-negative breast cancer, which often have limited treatment options.","specificNumbers":"","methodology":"The study is a review of existing literature on CPPs and their applications in cancer treatment.","limitations":"As a review, the study does not present original experimental data and relies on existing literature."},{"rthcId":"RPEP-06119","title":"Cathelicidin-NV from Nanorana ventripunctata effectively protects HaCaT cells, ameliorating ultraviolet B-induced skin photoaging.","authors":"Feng, Guizhu; Wei, Lin; Che, Helong; Shen, Yan; Mi, Kai; Bian, Hui; Yang, Hailong; Wu, Jing; Mu, Lixian","year":2022,"journal":"Peptides, 150, 170712","doi":"10.1016/j.peptides.2021.170712","pmid":"34929265","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Cathelicidin-NV reduced DNA fragmentation and apoptosis in HaCaT cells exposed to UVB.","whyItMatters":"Understanding how cathelicidin-NV protects skin cells could lead to new treatments for UV-induced skin aging. This research highlights the potential of frog-derived proteins in skincare applications.","specificNumbers":"","methodology":"The study involved treating HaCaT skin cells and mice with cathelicidin-NV and assessing its protective effects against UVB-induced damage.","limitations":"The study was conducted in vitro and in mice, so results may not directly translate to humans."},{"rthcId":"RPEP-06120","title":"A novel immunopeptidomic-based pipeline for the generation of personalized oncolytic cancer vaccines.","authors":"Feola, Sara; Chiaro, Jacopo; Martins, Beatriz; Russo, Salvatore; Fusciello, Manlio; Ylösmäki, Erkko; Bonini, Chiara; Ruggiero, Eliana; Hamdan, Firas; Feodoroff, Michaela; Antignani, Gabriella; Viitala, Tapani; Pesonen, Sari; Grönholm, Mikaela; Branca, Rui M M; Lehtiö, Janne; Cerullo, Vincenzo","year":2022,"journal":"eLife, 11","doi":"10.7554/eLife.71156","pmid":"35314027","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The study identified six peptide candidates that successfully controlled tumors in mice.","whyItMatters":"This research addresses key challenges in cancer vaccine development, potentially leading to more effective treatments for patients. It sets the stage for future human trials.","specificNumbers":"","methodology":"The researchers used immunoprecipitation and mass spectrometry to isolate peptides, followed by RNAseq analysis and functional assays to select the best candidates.","limitations":"The study was conducted in a murine model, and results may not directly translate to humans. Further validation in clinical settings is needed."},{"rthcId":"RPEP-06121","title":"The Safety and Efficacy of Calcitonin Gene-Related Peptide (CGRP) Monoclonal Antibodies for the Preventive Treatment of Migraine: A Protocol for Multiple-Treatment Systematic Review and Meta-Analysis.","authors":"Fernández-Bravo-Rodrigo, Jaime; Pascual-Morena, Carlos; Flor-García, Amparo; Saz-Lara, Alicia; Sequí-Dominguez, Irene; Álvarez-Bueno, Celia; Barreda-Hernández, Dolores; Cavero-Redondo, Iván","year":2022,"journal":"International journal of environmental research and public health, 19(3)","doi":"10.3390/ijerph19031753","pmid":"35162776","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review will assess the impact of CGRP monoclonal antibodies on monthly migraine days and headache severity.","whyItMatters":"Understanding the safety and efficacy of CGRP monoclonal antibodies can improve migraine management and patient quality of life. This research could guide treatment decisions for healthcare providers.","specificNumbers":"","methodology":"A systematic review and meta-analysis will be conducted using data from multiple databases, focusing on randomized trials and real-world studies.","limitations":"The study is a protocol and does not present results yet; actual outcomes will depend on the quality and quantity of included studies."},{"rthcId":"RPEP-06122","title":"Fixed-ratio combination of insulin glargine plus lixisenatide (iGlarLixi) improves ß-cell function in people with type 2 diabetes.","authors":"Ferrannini, Ele; Niemoeller, Elisabeth; Dex, Terry; Servera, Soraly; Mari, Andrea","year":2022,"journal":"Diabetes, obesity & metabolism, 24(6), 1159-1165","doi":"10.1111/dom.14688","pmid":"35257461","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"After 26 weeks, iGlarLixi produced a 35% median increase in beta-cell glucose sensitivity compared to GLP-1RA alone (p=0.0032). HbA1c decreased significantly more with iGlarLixi than with GLP-1RA alone (p<0.0001).\n\nNotably, iGlarLixi reduced both fasting and stimulated insulin secretion (both p<0.0001 vs. GLP-1RA), indicating that the beta cells were being spared from overproduction while functioning more efficiently. The incremental meal tolerance test glucose area also showed a larger reduction with iGlarLixi (p<0.0001). Body weight increased modestly in the iGlarLixi group (+1.7 kg, p<0.0001). In the GLP-1RA-only group, despite weight loss and HbA1c improvement, no beta-cell function parameters changed significantly.","whyItMatters":"Beta-cell dysfunction is the core defect driving type 2 diabetes progression. Finding that iGlarLixi not only improves blood sugar control but actually improves beta-cell function and spares insulin production suggests it may help preserve beta-cell health over time. This is a shift from simply treating high blood sugar to potentially modifying the underlying disease process.","specificNumbers":"","methodology":"Post-hoc analysis of the LixiLan-G randomized trial (NCT02787551) including 351 participants with type 2 diabetes on metformin. Participants were randomized to iGlarLixi (n=189) or continued daily/weekly GLP-1RA (n=162) for 26 weeks. Beta-cell function was assessed using 2-hour meal tolerance tests with timed glucose and C-peptide measurements at baseline and week 26, analyzed with mathematical modeling to derive insulin secretion and glucose sensitivity parameters.","limitations":"This was a post-hoc analysis of a clinical trial, not designed primarily to assess beta-cell function. The 26-week duration may not capture longer-term effects on beta-cell health. The modest weight gain with iGlarLixi is a trade-off compared to the weight loss seen with GLP-1RA alone. Only participants on metformin were included, limiting generalizability. Mathematical modeling of beta-cell function is an indirect assessment."},{"rthcId":"RPEP-06123","title":"Glucagon-Like Peptide-1 Receptor Agonists in Type 2 Diabetes Mellitus and Cardiovascular Disease: The Past, Present, and Future.","authors":"Ferrari, Filipe; Scheffel, Rafael S; Martins, Vítor M; Santos, Raul D; Stein, Ricardo","year":2022,"journal":"American journal of cardiovascular drugs : drugs, devices, and other interventions, 22(4), 363-383","doi":"10.1007/s40256-021-00515-4","pmid":"34958423","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review consolidates evidence from six major cardiovascular outcome trials:\n\n- Five human GLP-1-based and one exendin-based GLP-1RA reduced atherosclerotic cardiovascular events in T2DM patients at high cardiovascular risk\n- Meta-analysis showed reduction in major adverse cardiovascular events (MACE) and all-cause mortality versus placebo\n- Benefits were consistent regardless of structural homology (exendin-based vs. human GLP-1-based)\n- Additional benefits: prevention of macroalbuminuria onset (kidney protection), blood pressure reduction, significant weight loss\n- Safety: low hypoglycemia risk, no increase in pancreatitis events\n- Cardiovascular benefits appear independent of glycemic control, suggesting direct protective mechanisms","whyItMatters":"For decades, diabetes treatment focused on lowering blood sugar, but cardiovascular events remained the leading cause of death in diabetic patients. GLP-1RAs changed this paradigm by demonstrating that a diabetes drug could actually prevent heart attacks, strokes, and death. The fact that these benefits are independent of glucose control suggests GLP-1 drugs treat the cardiovascular disease itself, not just the diabetes. This has fundamentally changed treatment guidelines and how clinicians think about managing type 2 diabetes.","specificNumbers":"","methodology":"Narrative review synthesizing evidence from randomized controlled trials of GLP-1RAs with cardiovascular outcomes endpoints, including meta-analyses of six major cardiovascular outcome trials. The review also covers real-world evidence, mechanistic data, safety profiles, and current guideline recommendations from European and American societies.","limitations":"As a narrative review, the paper reflects selective literature coverage rather than a systematic meta-analysis. The cardiovascular outcome trials were conducted in high-risk T2DM patients, and benefits may differ in lower-risk populations or non-diabetic individuals. Not all GLP-1RAs have demonstrated cardiovascular benefit in dedicated outcome trials. The review was published before the latest trial data (e.g., SELECT trial in non-diabetic obesity), so the most recent evidence is not captured."},{"rthcId":"RPEP-06124","title":"Tuning Peptide Structure and Function through Fluorobenzene Stapling.","authors":"Fischer, Niklas H; Fumi, Erik; Oliveira, Maria Teresa; Thulstrup, Peter W; Diness, Frederik","year":2022,"journal":"Chemistry (Weinheim an der Bergstrasse, Germany), 28(8), e202103788","doi":"10.1002/chem.202103788","pmid":"34897848","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A catalyst-free fluorobenzene stapling method was developed for cysteine-containing peptides that enables fine-tuning of macrocyclic peptide structure by selecting different regioisomers (ortho, meta, or para) of the fluorobenzene linker. When applied to melanocortin receptor agonists, the method generated a library of potent macrocyclic ligands from the same linear precursor, with small but significant differences in potency and efficacy depending on the staple geometry. NMR and circular dichroism confirmed that different stapling configurations tune the peptide's secondary structure.","whyItMatters":"Cyclic peptides are among the most promising next-generation drug candidates, but existing methods to create them offer limited control over the final shape. This fluorobenzene stapling approach gives chemists a simple way to generate multiple structural variants from a single peptide sequence, enabling rapid optimization of biological activity — a capability that could accelerate peptide drug discovery across many therapeutic areas.","specificNumbers":"","methodology":"The researchers developed a catalyst-free stapling reaction using fluorobenzene linkers that react with cysteine residues in peptides. Stapling was performed either on unprotected linear peptides in solution or directly on-resin after solid-phase peptide synthesis. Structural characterization used NMR spectroscopy and circular dichroism. The method was validated by generating a library of macrocyclic melanocortin receptor agonists with ortho, meta, and para linker configurations, which were tested for receptor potency and efficacy.","limitations":"All experiments were conducted in vitro — the biological stability advantages of the cyclic peptides were not tested in vivo. The method was demonstrated on melanocortin receptor agonists only; generalizability to other peptide targets is inferred but not proven. Specific potency values and fold-differences between regioisomers are not reported in the abstract."},{"rthcId":"RPEP-06125","title":"Development and Validation of an LC-MS/MS Method for Simultaneous Determination of Short Peptide-Based Drugs in Human Blood Plasma.","authors":"Fisher, Elizaveta N; Melnikov, Evgeny S; Gegeckori, Vladimir; Potoldykova, Natalya V; Enikeev, Dmitry V; Pavlenko, Kirill A; Agatonovic-Kustrin, Snezana; Morton, David W; Ramenskaya, Galina V","year":2022,"journal":"Molecules (Basel, Switzerland), 27(22)","doi":"10.3390/molecules27227831","pmid":"36431933","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The method showed linearity from 0.5-20 ng/mL with correlation coefficients of 0.998-0.999.","whyItMatters":"This method enhances the ability to study peptide drugs' pharmacokinetics, which is crucial for developing effective treatments. Accurate measurement of these drugs can lead to better patient outcomes.","specificNumbers":"","methodology":"The study utilized HPLC-ESI-MS/MS with solid-phase extraction for sample preparation.","limitations":"The study does not address the method's applicability to other biological matrices or potential interferences."},{"rthcId":"RPEP-06126","title":"Impact of Gastrointestinal Digestion Simulation on the Formation of Angiotensin-I-Converting Enzyme Inhibitory (ACE-I) Peptides from Germinated Lamtoro Gung Flour.","authors":"Fitriani, Aprilia; Indrati, Retno; Marsono, Yustinus; Supriyadi, Supriyadi","year":2022,"journal":"Foods (Basel, Switzerland), 11(23)","doi":"10.3390/foods11233769","pmid":"36496578","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The 180 min digestion simulation resulted in 89.70% ACE-I activity, but no increase from GID was found.","whyItMatters":"Understanding how digestion affects peptide activity can inform food processing and health benefits of germinated grains. This research may help in developing functional foods with cardiovascular benefits.","specificNumbers":"","methodology":"The study simulated gastrointestinal digestion using commercial enzymes pepsin and pancreatin, analyzing the resulting ACE-I activity and peptide characteristics.","limitations":"The study focused solely on in vitro simulations, which may not fully replicate human digestion."},{"rthcId":"RPEP-06127","title":"Clinical perspectives on the use of the GIP/GLP-1 receptor agonist tirzepatide for the treatment of type-2 diabetes and obesity.","authors":"Gallwitz, Baptist","year":2022,"journal":"Frontiers in endocrinology, 13, 1004044","doi":"10.3389/fendo.2022.1004044","pmid":"36313764","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tirzepatide leads to significant reductions in glycemic parameters and body weight, outperforming standard therapies.","whyItMatters":"Tirzepatide represents a new approach in diabetes and obesity treatment, potentially improving patient outcomes. Its dual-action mechanism may offer advantages over existing therapies.","specificNumbers":"","methodology":"The article summarizes clinical studies and outcomes related to tirzepatide's efficacy.","limitations":"The article primarily reviews existing studies and may not address long-term effects or broader population impacts."},{"rthcId":"RPEP-06128","title":"Cyclic-di-GMP stimulates keratinocyte innate immune responses and attenuates methicillin-resistant Staphylococcus aureus colonization in a murine skin wound infection model.","authors":"Gao, Shuai; Khan, Abidullah; Chen, Xuhong; Xiao, Guohui; van der Veen, Stijn; Chen, Yin; Lin, Xu'ai","year":2022,"journal":"BMC microbiology, 22(1), 176","doi":"10.1186/s12866-022-02583-1","pmid":"35804301","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Cyclic-di-GMP reduced MRSA colonization by up to 1,100-fold in mice.","whyItMatters":"With rising antibiotic resistance, c-di-GMP offers a potential new approach to treat MRSA infections. Its ability to enhance immune responses could lead to better outcomes for patients with skin wounds.","specificNumbers":"","methodology":"The study involved stimulating human skin cells with c-di-GMP and testing its effects in a mouse model of MRSA skin infection.","limitations":"The study was conducted in a mouse model, which may not fully replicate human responses. Further research is needed to confirm efficacy in humans."},{"rthcId":"RPEP-06129","title":"Effects of substance P on human cerebral microvascular endothelial cell line hCMEC/D3 are mediated exclusively through a truncated NK-1 receptor and depend on cell confluence.","authors":"Gao, Xin; Frakich, Nanci; Filippini, Perla; Edwards, Laura J; Vinkemeier, Uwe; Gran, Bruno; Tanasescu, Radu; Bayraktutan, Ulvi; Colombo, Sergio; Constantinescu, Cris S","year":2022,"journal":"Neuropeptides, 95, 102265","doi":"10.1016/j.npep.2022.102265","pmid":"35696961","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Substance P reduced expression of the tight junction protein occludin in human brain endothelial cells, but only when cells were at low confluence — at full confluence, no effect was observed. SP acted exclusively through a truncated form of the NK-1 receptor and stimulated Erk2 phosphorylation without triggering inflammatory cytokines (IL-6, IL-8) or ICAM-1. SP also restored nitric oxide production in cells exposed to TNF-α. Importantly, SP did not trigger intracellular calcium release, indicating the truncated NK-1R signals differently from the full-length receptor.","whyItMatters":"The blood-brain barrier is critical for brain protection, and understanding how neuropeptides like Substance P regulate its permeability has implications for neurological diseases including multiple sclerosis, stroke, and brain tumors. The finding that SP's effects depend on cell state (confluence) adds important nuance for designing neuropeptide-targeted therapies.","specificNumbers":"Occludin reduced at low confluence only · Erk2 phosphorylation activated · no IL-6/IL-8/ICAM-1 changes · NO production restored under TNF-α · no intracellular calcium release","methodology":"Human brain microvascular endothelial cells (hCMEC/D3 line) were treated with Substance P at different confluence states. Researchers measured mRNA and protein expression of BBB-related genes (occludin), NK-1R receptor expression, Erk2 phosphorylation, inflammatory marker levels (IL-6, IL-8, ICAM-1), nitric oxide production under TNF-α challenge, and intracellular calcium signaling.","limitations":"Single immortalized cell line (hCMEC/D3) that expresses only the truncated NK-1R, which may not represent the full spectrum of SP signaling in native brain endothelium. In vitro conditions cannot fully replicate the complex blood-brain barrier environment in vivo. The functional consequences of reduced occludin on actual BBB permeability were not directly measured."},{"rthcId":"RPEP-06130","title":"Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial.","authors":"Garvey, W Timothy; Batterham, Rachel L; Bhatta, Meena; Buscemi, Silvio; Christensen, Louise N; Frias, Juan P; Jódar, Esteban; Kandler, Kristian; Rigas, Georgia; Wadden, Thomas A; Wharton, Sean","year":2022,"journal":"Nature medicine, 28(10), 2083-2091","doi":"10.1038/s41591-022-02026-4","pmid":"36216945","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06131","title":"Microencapsulated bioactive peptides from brewer's spent grain promotes antihypertensive and antidiabetogenic effects on a hypertensive and insulin-resistant rat model.","authors":"Garzón, Antonela G; Ferreira, María Del Rosario; Cian, Raul E; Oliva, Maria Eugenia; D'Alessandro, Maria Eugenia; Drago, Silvina R","year":2022,"journal":"Journal of food biochemistry, 46(10), e14283","doi":"10.1111/jfbc.14283","pmid":"35746832","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The SRD-P group showed lower systolic pressure and decreased enzyme activities compared to the SRD group, reaching levels similar to the control diet.","whyItMatters":"These findings highlight the potential of using brewer's spent grain peptides as a functional food ingredient to combat hypertension and diabetes, addressing significant health issues.","specificNumbers":"","methodology":"Rats were divided into groups and fed different diets for 100 days, with blood pressure and various metabolic parameters monitored.","limitations":"The study was conducted on rats, so results may not directly apply to humans; further research is needed."},{"rthcId":"RPEP-06132","title":"In vitro inhibition of glucose gastro-intestinal enzymes and antioxidant activity of hydrolyzed collagen peptides from different species.","authors":"Gaspardi, Ana Lais Andrade; da Silva, Daniele Cristina; Ponte, Luis Gustavo Saboia; Galland, Fabiana; da Silva, Vera Sonia Nunes; Simabuco, Fernando Moreira; Bezerra, Rosângela Maria Neves; Pacheco, Maria Teresa Bertoldo","year":2022,"journal":"Journal of food biochemistry, 46(12), e14383","doi":"10.1111/jfbc.14383","pmid":"36181391","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Fish collagen showed 96.36% DNA protection and porcine collagen had antioxidant activity of 67.08 μmol Trolox Eq./g.","whyItMatters":"Understanding the varying effects of collagen peptides can lead to new health supplements that may help manage diabetes and improve overall health.","specificNumbers":"","methodology":"The study involved in vitro tests to evaluate the biological activities of hydrolyzed collagen peptides from different animal sources.","limitations":"The study was conducted in vitro, so results may not directly translate to human health outcomes."},{"rthcId":"RPEP-06133","title":"Screening for effective cell-penetrating peptides with minimal impact on epithelial cells and gut commensals in vitro.","authors":"Gelli, Hitesh P; Vazquez-Uribe, Ruben; Sommer, Morten Otto Alexander","year":2022,"journal":"Frontiers in pharmacology, 13, 1049324","doi":"10.3389/fphar.2022.1049324","pmid":"36408245","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Out of 9 cell-penetrating peptides tested, 4 significantly improved intestinal paracellular permeability without compromising cell health. Among these, the synthetic CPPs Shuffle and Penetramax were the top performers, increasing permeability at 50 µM concentration while having only small to moderate antimicrobial effects on tested gut commensal strains. The other 4 CPPs that improved permeability had more substantial negative effects on nearly all tested gut bacteria.","whyItMatters":"Many promising drugs fail because they can't be absorbed orally, forcing patients to use injections instead. Finding peptides that safely improve gut absorption — without destroying beneficial gut bacteria — could make oral delivery feasible for a much wider range of therapeutics, improving patient compliance and quality of life.","specificNumbers":"","methodology":"Researchers tested 9 CPPs using a differentiated Caco-2 epithelial monolayer model (a standard lab model of the intestinal barrier). Cytotoxicity was measured with Cytotox Red dye staining, cell viability with AlamarBlue staining, and paracellular permeability by transport assays. The 4 best-performing CPPs were then tested against 10 representative gut bacteria strains using microbroth dilution assays.","limitations":"All experiments were conducted in vitro using cell monolayers and isolated bacterial strains, which may not fully reflect the complex environment of the human gut. The study did not test actual drug absorption with these CPPs, only permeability markers. In vivo studies are needed to confirm safety and efficacy in living organisms."},{"rthcId":"RPEP-06134","title":"Synthesis of Cell-Penetrating Peptide Coated Silica Nanoparticles and Their Physicochemical and Biological Characterization.","authors":"Gessner, Isabel; Klimpel, Annika; Neundorf, Ines","year":2022,"journal":"Methods in molecular biology (Clifton, N.J.), 2383, 105-117","doi":"10.1007/978-1-0716-1752-6_7","pmid":"34766285","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Silica nanoparticles modified with CPPs showed improved cellular uptake.","whyItMatters":"This research is significant as it explores new ways to improve drug delivery systems, potentially enhancing the effectiveness of therapies. Understanding how to better deliver therapeutics at the cellular level could lead to advancements in treatment options.","specificNumbers":"","methodology":"The study involved synthesizing silica nanoparticles and modifying their surfaces with CPPs, followed by characterization through various physicochemical and biological assays.","limitations":"The study does not specify the exact efficiency of drug delivery or the long-term effects of these nanoparticles in vivo."},{"rthcId":"RPEP-06135","title":"Growth differentiation factor 15 (GDF15) and semaglutide inhibit food intake and body weight through largely distinct, additive mechanisms.","authors":"Ghidewon, M; Wald, H S; McKnight, A D; De Jonghe, B C; Breen, D M; Alhadeff, A L; Borner, T; Grill, H J","year":2022,"journal":"Diabetes, obesity & metabolism, 24(6), 1010-1020","doi":"10.1111/dom.14663","pmid":"35129264","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Combined treatment with GDF15 and semaglutide resulted in greater weight loss and food intake suppression compared to either treatment alone.","whyItMatters":"Understanding how these treatments work can lead to more effective obesity therapies. The distinct mechanisms suggest potential for combination therapies in weight management.","specificNumbers":"","methodology":"The study used rat experiments to assess the effects of GDF15 and semaglutide on food intake and weight loss through various behavioral and neural mechanisms.","limitations":"The study was conducted in rats, and results may not directly translate to humans."},{"rthcId":"RPEP-06136","title":"S-Benzyl cysteine based cyclic dipeptide super hydrogelator: Enhancing efficacy of an anticancer drug via sustainable release.","authors":"Ghosh, Saswati; Nag, Sayoni; Saha, Krishna Das; Banerji, Biswadip","year":2022,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 28(8), e3403","doi":"10.1002/psc.3403","pmid":"35001443","tags":[],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"A cyclic dipeptide made from leucine and S-benzyl cysteine (P1) self-assembled into a hydrogel at body temperature and physiological pH. The hydrogel was remarkably stable — lasting over a year without degradation, tolerating pH 6–12, and being thermoreversible.\n\nWhen loaded with the cancer drug 5-fluorouracil (5FU), the hydrogel provided sustained drug release and significantly enhanced anticancer activity against colorectal cancer cells (HCT116), lowering the effective dose (IC50) of 5FU substantially. The dipeptide itself showed almost no toxicity to cancer cells even at high concentrations, making it a safe carrier material.","whyItMatters":"Cancer drugs like 5FU are effective but cause severe side effects because they hit healthy cells along with cancer cells. A delivery system that slowly releases the drug at the tumor site could improve efficacy while reducing side effects. This cyclic dipeptide hydrogel achieves exactly that — and it's made from just two amino acids, making it biocompatible, biodegradable, and potentially cheap to manufacture. The year-plus stability and body-temperature gelation make it particularly practical for clinical applications.","specificNumbers":"2 amino acids (Leu + S-Bzl-Cys) · stable >1 year · pH 6–12 tolerance · thermoreversible · IC50 of 5FU significantly reduced · minimal cytotoxicity of carrier · nanofibrillar network structure · antiparallel β-sheet arrangement","methodology":"Lab-based biomaterial study. Researchers synthesized cyclic dipeptide P1 and characterized its hydrogel using rheology (mechanical strength), atomic force microscopy, scanning electron microscopy, circular dichroism, FTIR spectroscopy, and ThT binding assay. Drug loading and release were tested with 5-fluorouracil, and anticancer activity was measured against HCT116 colorectal cancer cells in vitro.","limitations":"Entirely in vitro — no animal or human testing. Drug release kinetics in a living body (with blood flow, immune response, and enzymatic degradation) may differ from lab conditions. No comparison with existing drug delivery systems. Tumor-targeting specificity was not assessed. Scalability of manufacturing was not addressed."},{"rthcId":"RPEP-06137","title":"Weight-centric treatment of type 2 diabetes mellitus.","authors":"Ghusn, Wissam; Hurtado, Maria Daniela; Acosta, Andres","year":2022,"journal":"Obesity pillars, 4, 100045","doi":"10.1016/j.obpill.2022.100045","pmid":"37990663","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Medications like insulin and sulfonylureas are associated with weight gain, while GLP-1 agonists and metformin promote weight loss.","whyItMatters":"Understanding the weight effects of diabetes medications can lead to better treatment strategies for managing T2DM. A weight-centric approach may improve patient health and reduce complications.","specificNumbers":"","methodology":"The review analyzed studies from multiple databases, focusing on the effects of T2DM medications on body weight from 1950 to 2022.","limitations":"The review is based on existing literature and may not include the latest studies or emerging medications."},{"rthcId":"RPEP-06138","title":"Calreticulin mutant myeloproliferative neoplasms induce MHC-I skewing, which can be overcome by an optimized peptide cancer vaccine.","authors":"Gigoux, Mathieu; Holmström, Morten O; Zappasodi, Roberta; Park, Joseph J; Pourpe, Stephane; Bozkus, Cansu Cimen; Mangarin, Levi M B; Redmond, David; Verma, Svena; Schad, Sara; George, Mariam M; Venkatesh, Divya; Ghosh, Arnab; Hoyos, David; Molvi, Zaki; Kamaz, Baransel; Marneth, Anna E; Duke, William; Leventhal, Matthew J; Jan, Max; Ho, Vincent T; Hobbs, Gabriela S; Knudsen, Trine Alma; Skov, Vibe; Kjær, Lasse; Larsen, Thomas Stauffer; Hansen, Dennis Lund; Lindsley, R Coleman; Hasselbalch, Hans; Grauslund, Jacob H; Lisle, Thomas L; Met, Özcan; Wilkinson, Patrick; Greenbaum, Benjamin; Sepulveda, Manuel A; Chan, Timothy; Rampal, Raajit; Andersen, Mads H; Abdel-Wahab, Omar; Bhardwaj, Nina; Wolchok, Jedd D; Mullally, Ann; Merghoub, Taha","year":2022,"journal":"Science translational medicine, 14(649), eaba4380","doi":"10.1126/scitranslmed.aba4380","pmid":"35704596","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Heteroclitic CALRMUT peptides elicited a CD8+ T cell response in patients, unlike native peptides.","whyItMatters":"This research highlights a potential new approach to cancer vaccination that could improve outcomes for patients with specific genetic mutations.","specificNumbers":"","methodology":"The study analyzed MHC-I allele frequencies in patients and tested immune responses to modified peptides in human samples and mouse models.","limitations":"The study primarily focused on specific patient cohorts, which may limit the generalizability of the findings."},{"rthcId":"RPEP-06139","title":"Association of obesity in T2DM with differential polymorphism of ghrelin, growth hormone secretagogue receptor-1 and telomeres maintenance genes.","authors":"Giha, Hayder A; Joatar, Faris E; AlDehaini, Dhuha M B; Malalla, Zainab H A; Ali, Muhalab E; Al Qarni, Ali A","year":2022,"journal":"Hormone molecular biology and clinical investigation, 43(3), 297-306","doi":"10.1515/hmbci-2021-0063","pmid":"35446515","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The ACYP2 rs6713088 CC genotype was the standout finding: it was significantly under-represented in obese diabetics (17.8%) compared to non-obese diabetics (40.4%, p=0.01) and showed a gradient across 4 BMI grades (p=0.025). Paradoxically, the same genotype was over-represented in obese non-diabetics compared to non-obese non-diabetics (50% vs 27.6%, p=0.04), suggesting its role differs depending on diabetes status.\n\nGhrelin (GHRL rs27647C/T), ghrelin receptor (GHSR rs509030G/C), and TERC (rs12696304G/C) minor allele frequencies were significantly lower in normal-BMI diabetic patients (p=0.034, 0.008, and 0.011, respectively), suggesting these variants may contribute to obesity susceptibility within the diabetic population.","whyItMatters":"Understanding why some diabetics become obese while others don't could enable more personalized treatment. The finding that ghrelin-related genetic variants differ across BMI categories in diabetes is particularly interesting because ghrelin is a peptide hormone that could be therapeutically targeted. If specific genetic profiles predict obesity risk in diabetes, treatments could be tailored accordingly — for example, choosing GLP-1RA therapy for patients with high-risk ghrelin variants.","specificNumbers":"","methodology":"Two cross-sectional studies conducted in Saudi Arabia (2013) and Kuwait (2019) enrolling 216 type 2 diabetes patients and 193 non-diabetic controls. Participants were grouped by obesity status and sub-grouped into 4 BMI categories (normal, overweight, obese, severely obese). Eight SNPs in 5 genes (ghrelin, GHSR, ACYP2, TERC, and others) were genotyped by real-time PCR from fasting blood samples.","limitations":"The cross-sectional design cannot establish causation. Sample sizes were moderate (216 T2DM patients, 193 controls), limiting statistical power for subgroup analyses. The study was conducted in two Middle Eastern populations and may not generalize to other ethnic groups. The two study sites used different gene panels, limiting direct comparison. Multiple testing correction was not described. The functional significance of the identified SNPs needs further investigation."},{"rthcId":"RPEP-06140","title":"Advances in the Development of Nonpeptide Small Molecules Targeting Ghrelin Receptor.","authors":"Giorgioni, Gianfabio; Del Bello, Fabio; Quaglia, Wilma; Botticelli, Luca; Cifani, Carlo; Micioni Di Bonaventura, E; Micioni Di Bonaventura, M V; Piergentili, Alessandro","year":2022,"journal":"Journal of medicinal chemistry, 65(4), 3098-3118","doi":"10.1021/acs.jmedchem.1c02191","pmid":"35157454","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The study identifies several nonpeptide small molecules that act on GHS-R1a, with promising pharmacological effects.","whyItMatters":"Understanding how these new molecules interact with the ghrelin receptor could lead to innovative treatments for metabolic disorders. This research could significantly impact how we manage conditions related to appetite and energy regulation.","specificNumbers":"","methodology":"The study is a perspective review focusing on recent developments in nonpeptide small molecules targeting GHS-R1a.","limitations":"The study is a review and does not provide original experimental data or clinical trial results."},{"rthcId":"RPEP-06141","title":"Investigating 3R In Vivo Approaches for Bio-Distribution and Efficacy Evaluation of Nucleic Acid Nanocarriers: Studies on Peptide-Mimicking Ionizable Lipid.","authors":"Giselbrecht, Julia; Pinnapireddy, Shashank Reddy; Alioglu, Fatih; Sami, Haider; Sedding, Daniel; Erdmann, Frank; Janich, Christopher; Schulz-Siegmund, Michaela; Ogris, Manfred; Bakowsky, Udo; Langner, Andreas; Bussmann, Jeroen; Wölk, Christian","year":2022,"journal":"Small (Weinheim an der Bergstrasse, Germany), 18(18), e2107768","doi":"10.1002/smll.202107768","pmid":"35355412","tags":[],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"A peptide-mimicking ionizable lipid formulation (OH4:DOPE) successfully delivered DNA and mRNA into living tissues using ethical animal models that reduce the need for mammalian experiments. In zebrafish embryos, the lipid nanoparticles selectively transfected blood vessel endothelial cells, particularly in the endocardium (heart lining). The chicken egg membrane model also showed effective tissue transfection.\n\nPilot studies in mice confirmed that the transfection patterns seen in simpler models correlated with mammalian results, validating these alternative models as reliable screening tools for nucleic acid delivery systems.","whyItMatters":"Getting genetic material (DNA, mRNA) into specific cells inside the body is one of the biggest challenges in medicine — it's the bottleneck for gene therapy, mRNA vaccines, and RNA-based drugs. This study shows that a peptide-inspired lipid can deliver nucleic acids specifically to blood vessel cells, and that researchers can test these delivery systems using zebrafish and chicken egg models instead of mammals, making the drug development pipeline both more ethical and faster.","specificNumbers":"OH4:DOPE formulation · DNA and mRNA delivered · endothelial cell transfection confirmed · endocardium targeting observed · 3 model systems used (chicken membrane, zebrafish, mice)","methodology":"Multi-model in vivo study. Researchers tested the OH4:DOPE lipid formulation's ability to deliver DNA and mRNA using three models: chicken chorioallantoic membrane (CAM), zebrafish embryos (for biodistribution and transfection screening), and pilot mouse studies for mammalian correlation. The approach followed 3R guidelines (replace, reduce, refine) to minimize animal use.","limitations":"Zebrafish and chicken embryo models, while physiologically complex, don't fully replicate human cardiovascular biology. Mouse pilot studies were limited in scope. No human tissue or clinical data. The peptide-mimicking lipid structure may behave differently in human blood with its complex protein corona. Long-term safety and immunogenicity were not assessed."},{"rthcId":"RPEP-06142","title":"Once daily oral relugolix combination therapy versus placebo in patients with endometriosis-associated pain: two replicate phase 3, randomised, double-blind, studies (SPIRIT 1 and 2).","authors":"Giudice, Linda C; As-Sanie, Sawsan; Arjona Ferreira, Juan C; Becker, Christian M; Abrao, Mauricio S; Lessey, Bruce A; Brown, Eric; Dynowski, Krzysztof; Wilk, Krzysztof; Li, Yulan; Mathur, Vandana; Warsi, Qurratul Ann; Wagman, Rachel B; Johnson, Neil P","year":2022,"journal":"Lancet (London, England), 399(10343), 2267-2279","doi":"10.1016/S0140-6736(22)00622-5","pmid":"35717987","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06143","title":"Vasopressin and Its Analogues: From Natural Hormones to Multitasking Peptides.","authors":"Glavaš, Mladena; Gitlin-Domagalska, Agata; Dębowski, Dawid; Ptaszyńska, Natalia; Łęgowska, Anna; Rolka, Krzysztof","year":2022,"journal":"International journal of molecular sciences, 23(6)","doi":"10.3390/ijms23063068","pmid":"35328489","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Vasopressin analogues like desmopressin and terlipressin have specific therapeutic uses.","whyItMatters":"Understanding vasopressin analogues can lead to better treatment options for various medical conditions. Their potential use in COVID-19 treatment is particularly significant in current health contexts.","specificNumbers":"","methodology":"The study is a review of existing literature on vasopressin and its analogues.","limitations":"The study is primarily a review and does not present new experimental data or clinical trials."},{"rthcId":"RPEP-06144","title":"On-Resin Peptide Cyclization Using the 3-Amino-4-(Methylamino)Benzoic Acid MeDbz Linker.","authors":"Gless, Bengt H; Olsen, Christian A","year":2022,"journal":"Methods in molecular biology (Clifton, N.J.), 2371, 101-115","doi":"10.1007/978-1-0716-1689-5_6","pmid":"34596845","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The study introduces a cyclization methodology for cyclic thiodepsipeptides and cyclic homodetic peptides using the MeDbz linker.","whyItMatters":"Cyclic peptides have significant potential in drug discovery due to their enhanced binding properties. This new method may streamline the synthesis of these compounds, making them more accessible for research and therapeutic applications.","specificNumbers":"","methodology":"The researchers developed an on-resin cyclization method and described three additional one-pot procedures for peptide modification.","limitations":"The study primarily focuses on methodology without extensive biological validation of the synthesized peptides."},{"rthcId":"RPEP-06145","title":"Impact of DNA Prime/Protein Boost Vaccination against Campylobacter jejuni on Immune Responses and Gut Microbiota in Chickens.","authors":"Gloanec, Noémie; Dory, Daniel; Quesne, Ségolène; Béven, Véronique; Poezevara, Typhaine; Keita, Alassane; Chemaly, Marianne; Guyard-Nicodème, Muriel","year":2022,"journal":"Vaccines, 10(6)","doi":"10.3390/vaccines10060981","pmid":"35746589","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Vaccination led to a partial reduction in Campylobacter loads and changes in gut microbiota.","whyItMatters":"Campylobacter is a major food safety concern, and improving vaccination strategies could enhance poultry health and reduce zoonotic transmission.","specificNumbers":"","methodology":"The study involved vaccinating chickens and then challenging them with Campylobacter at 19 days old, comparing vaccinated and placebo groups.","limitations":"The study was conducted in specific-pathogen-free chickens, which may not fully represent commercial poultry conditions."},{"rthcId":"RPEP-06146","title":"Efficacy and tolerability of a hyaluronic acid-based serum and a peptide-rich cream for the face and neck in subjects with photodamaged skin.","authors":"Gold, Michael H; Biron, Julie A; Wilson, April; Nelson, Diane B","year":2022,"journal":"Journal of cosmetic dermatology, 21(8), 3458-3463","doi":"10.1111/jocd.14981","pmid":"35426967","tags":[],"studyType":"open-label-clinical","evidenceStrength":"low","keyFinding":"A 12-week skincare regimen combining a hyaluronic acid serum and a peptide-rich cream improved the appearance of sun-damaged skin on both face and neck. On the face, 79% of subjects showed improved skin texture, 50% showed reduced lines and wrinkles, and 44% showed improved skin tone. On the neck, improvements were seen in texture (68%), tone (48%), and lines/wrinkles (36%).\n\nNo adverse events were reported. All 17 subjects reported overall skin improvement and smoother-feeling skin. Eighty-eight percent said their skin looked more radiant, and 82% said it looked firmer.","whyItMatters":"Peptide-containing skincare products are increasingly popular, but many lack clinical testing. This study provides clinical data on a specific HA + peptide combination, showing measurable improvements in photodamaged skin over 12 weeks with no adverse effects. However, the absence of a placebo control limits the ability to attribute improvements specifically to the active ingredients.","specificNumbers":"n=17 · 12 weeks · Face: 79% texture improvement, 50% wrinkle improvement, 44% tone improvement · Neck: 68% texture, 48% tone, 36% wrinkles · 0 adverse events · 88% reported more radiant skin","methodology":"Open-label, single-arm study with 17 female subjects (mean age 52) with mild to moderate photodamage. Participants applied a hyaluronic acid serum and peptide-rich cream twice daily for 12 weeks. Changes in skin texture, tone, and lines/wrinkles were assessed on a 6-point grading scale. Subject satisfaction was surveyed and adverse events were tracked throughout.","limitations":"Very small sample size (n=17) with no control group, no blinding, and no placebo comparison — meaning improvements could be due to the moisturizing effect of any cream, the placebo effect, or natural variation. Only female participants were included. The specific peptides in the cream are not identified in the abstract, making it impossible to attribute results to particular peptide ingredients. The subjective satisfaction measures are prone to bias."},{"rthcId":"RPEP-06147","title":"The substance P/ neurokinin-1 receptor signaling pathway mediates metastasis in human colorectal SW480 cancer cells.","authors":"Golestaneh, Malihe; Firoozrai, Mohsen; Javid, Hossein; Hashemy, Seyed Isaac","year":2022,"journal":"Molecular biology reports, 49(6), 4893-4900","doi":"10.1007/s11033-022-07348-7","pmid":"35429316","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Substance P dose-dependently increased metastatic activity in human SW480 colorectal cancer cells across multiple measures: MMP-2 and MMP-9 enzymatic activity increased, gene expression of both metalloproteinases was upregulated, and cell migration increased in scratch assays.\n\nAprepitant (a neurokinin-1 receptor antagonist) significantly reversed all substance P-mediated metastatic effects (p < 0.001). This included reduced MMP-2/MMP-9 activity at both transcriptional and translational levels and decreased cell migration. The results identify the SP/NK1R pathway as a key metastatic driver in colorectal cancer and aprepitant as a potential anti-metastatic agent.","whyItMatters":"Colorectal cancer is among the deadliest cancers, and metastasis — not the primary tumor — is what kills most patients. Finding that an already-approved drug (aprepitant) can block a key metastatic pathway opens the door to rapid clinical testing. Drug repurposing avoids the years of safety testing required for new drugs, potentially bringing an anti-metastatic therapy to patients faster.","specificNumbers":"","methodology":"Human SW480 colorectal cancer cells were treated with varying concentrations of substance P, alone or combined with aprepitant. Cell viability was measured using the Resazurin assay. Metastatic potential was assessed by gelatin zymography (to measure MMP-2 and MMP-9 enzyme activity), RT-qPCR (gene expression), Western blot (protein expression), and scratch wound assay (cell migration).","limitations":"This was an in vitro study using a single colorectal cancer cell line (SW480), which may not represent the full heterogeneity of colorectal cancers. No animal models or clinical data were included. The concentrations of substance P and aprepitant used in the lab may not reflect what occurs in the tumor microenvironment. The study did not assess invasion through Matrigel or other 3D models that better simulate in vivo metastasis."},{"rthcId":"RPEP-06148","title":"The role of cholecystokinin and peptide YY in feed intake in Atlantic halibut (Hippoglossus hippoglossus) larvae.","authors":"Gomes, Ana S; Lygre, Endre; Harboe, Torstein; Zimmermann, Fabian; Jordal, Ann-Elise O; Hamre, Kristin; Rønnestad, Ivar","year":2022,"journal":"Neuropeptides, 91, 102202","doi":"10.1016/j.npep.2021.102202","pmid":"34741845","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CCK2 and PYYB mRNA expression was significantly higher in fed larvae, indicating a role in satiety.","whyItMatters":"Understanding how these hormones work can help improve feeding strategies for halibut larvae, potentially enhancing aquaculture practices.","specificNumbers":"","methodology":"The study measured mRNA expression of CCK and PYY in the brain and gut of halibut larvae after feeding them Artemia nauplii and attractants.","limitations":"The study focused on a specific life stage of halibut and used a limited range of attractants, which may not represent all feeding scenarios."},{"rthcId":"RPEP-06149","title":"Identification and Functional Analysis of a Defensin CcDef2 from Coridius chinensis.","authors":"Gong, Tao; Du, Juan; Li, Shang-Wei; Huang, Hai; Qi, Xiao-Lang","year":2022,"journal":"International journal of molecular sciences, 23(5)","doi":"10.3390/ijms23052789","pmid":"35269935","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CcDef2 showed significant antibacterial effects against three types of Gram-positive bacteria.","whyItMatters":"Understanding CcDef2's antibacterial properties could lead to new alternatives to traditional antibiotics, addressing antibiotic resistance issues.","specificNumbers":"","methodology":"The study involved bioinformatics analysis, gene expression profiling, and functional assays using recombinant CcDef2 expressed in E. coli.","limitations":"The study primarily focuses on a single peptide and its effects in vitro, which may not fully represent its efficacy in living organisms."},{"rthcId":"RPEP-06150","title":"Machine-learning-based approach for predicting response to anti-calcitonin gene-related peptide (CGRP) receptor or ligand antibody treatment in patients with migraine: A multicenter Spanish study.","authors":"Gonzalez-Martinez, Alicia; Pagán, Josué; Sanz-García, Ancor; García-Azorín, David; Rodríguez-Vico, Jaime Samuel; Jaimes, Alex; García, Andrea Gómez; de Terán, Javier Díaz; González-García, Nuria; Quintas, Sonia; Belascoaín, Rocío; Casas Limón, Javier; Latorre, Germán; Calle de Miguel, Carlos; Sierra, Álvaro; Guerrero-Peral, Ángel Luis; Trevino-Peinado, Cristina; Gago-Veiga, Ana Beatriz","year":2022,"journal":"European journal of neurology, 29(10), 3102-3111","doi":"10.1111/ene.15458","pmid":"35726393","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"ML models achieved an F1 score range of 0.70-0.97 and an AUC score range of 0.87-0.98.","whyItMatters":"Predicting treatment responses can lead to more personalized migraine management, improving patient outcomes. This research offers a practical tool for clinicians.","specificNumbers":"","methodology":"The study used a multicenter analysis of prospectively collected data, applying machine learning for predictive modeling.","limitations":"The study's findings may not generalize to all populations, and further validation in diverse settings is needed."},{"rthcId":"RPEP-06151","title":"Bioactive Peptide Fractions from Collagen Hydrolysate of Common Carp Fish Byproduct: Antioxidant and Functional Properties.","authors":"González-Serrano, Diego J; Hadidi, Milad; Varcheh, Matin; Jelyani, Aniseh Zarei; Moreno, Andres; Lorenzo, Jose M","year":2022,"journal":"Antioxidants (Basel, Switzerland), 11(3)","doi":"10.3390/antiox11030509","pmid":"35326159","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"PF4 showed the highest DPPH radical-scavenging activity (87%) at 1 mg/mL.","whyItMatters":"These findings highlight the potential of using fish byproducts to create natural antioxidants, which can benefit both food and health industries.","specificNumbers":"","methodology":"Collagen was hydrolyzed using alcalase enzyme, and various peptide fractions were analyzed for antioxidant and functional properties.","limitations":"The study was conducted in vitro, and results may not directly translate to in vivo applications."},{"rthcId":"RPEP-06152","title":"Enhanced oral absorption of insulin: hydrophobic ion pairing and a self-microemulsifying drug delivery system using a D-optimal mixture design.","authors":"Goo, Yoon Tae; Lee, Sangkil; Choi, Ji Yeh; Kim, Min Song; Sin, Gi Hyeong; Hong, Sun Ho; Kim, Chang Hyun; Song, Seh Hyon; Choi, Young Wook","year":2022,"journal":"Drug delivery, 29(1), 2831-2845","doi":"10.1080/10717544.2022.2118399","pmid":"36050870","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A self-microemulsifying drug delivery system (SMEDDS) using hydrophobic ion pairing achieved oral insulin absorption in diabetic rats with pharmacological availabilities of 3.23% at 50 IU/kg and 2.13% at 100 IU/kg. The optimized formulation protected insulin from gastrointestinal enzyme degradation and kept the majority of insulin within oil droplets during release. The formulation used an insulin complex with sodium n-octadecyl sulfate loaded into an optimized microemulsion with droplet sizes of 115.2 nm.","whyItMatters":"Insulin injections are the daily burden millions of diabetics live with. If insulin could be taken as a pill, it would transform diabetes management. This study demonstrates a formulation strategy that achieves measurable oral insulin absorption — small percentages, but proof that the approach works and can be optimized further.","specificNumbers":"","methodology":"Researchers first complexed insulin with sodium n-octadecyl sulfate (SOS) to make it more fat-soluble. They then used a D-optimal mixture design — a statistical optimization method — to create the best SMEDDS formulation from three components: Capmul MCM (9.31%), Labrasol (49.77%), and Tetraglycol (40.92%). The formulation was characterized for droplet size, insulin stability, and insulin leakage. Finally, it was administered orally to diabetic rats and blood glucose responses were measured to calculate pharmacological availability.","limitations":"The study was conducted in diabetic rats, not humans, and oral bioavailability was low (2–3%). Rat gastrointestinal physiology differs from humans in ways that affect oral absorption. Long-term stability of the formulation was not assessed. The study did not evaluate repeated dosing or potential toxicity of the formulation components."},{"rthcId":"RPEP-06153","title":"Clinical Recommendations to Manage Gastrointestinal Adverse Events in Patients Treated with Glp-1 Receptor Agonists: A Multidisciplinary Expert Consensus.","authors":"Gorgojo-Martínez, Juan J; Mezquita-Raya, Pedro; Carretero-Gómez, Juana; Castro, Almudena; Cebrián-Cuenca, Ana; de Torres-Sánchez, Alejandra; García-de-Lucas, María Dolores; Núñez, Julio; Obaya, Juan Carlos; Soler, María José; Górriz, José Luis; Rubio-Herrera, Miguel Ángel","year":2022,"journal":"Journal of clinical medicine, 12(1)","doi":"10.3390/jcm12010145","pmid":"36614945","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A multidisciplinary panel of 12 experts (endocrinologists, nephrologists, cardiologists, primary care physicians, internists, and diabetes educators) developed consensus recommendations for managing the gastrointestinal side effects of GLP-1 drugs. The guidelines cover how to properly escalate doses to reduce GI symptoms, what to do when nausea, vomiting, diarrhea, or constipation develop during treatment, and practical clinical scenarios that doctors encounter regularly. The goal is to keep patients on therapy rather than having them quit due to side effects.","whyItMatters":"GI side effects are the number one reason people stop taking GLP-1 drugs — and stopping means losing the blood sugar and weight loss benefits. Yet many patients quit simply because they or their doctors don't know how to manage the symptoms. This consensus provides the first structured, multi-specialty guidance specifically focused on GLP-1 GI side effect management, filling a gap that has real consequences for millions of patients.","specificNumbers":"","methodology":"An expert panel of 12 specialists across six medical disciplines (endocrinology, nephrology, primary care, cardiology, internal medicine, and diabetes nursing) met virtually to review evidence and clinical experience. They developed consensus recommendations through structured discussion, created clinical scenarios representing common situations, and designed infographics for both clinicians and patients.","limitations":"This is an expert consensus document, not a systematic review or clinical trial. Recommendations are based on the panel's clinical experience and interpretation of existing evidence, which may not always be backed by randomized trial data. The consensus was developed by Spanish experts and some recommendations may reflect regional practice patterns."},{"rthcId":"RPEP-06154","title":"The importance of an early onset of migraine prevention: an evidence-based, hypothesis-driven scoping literature review.","authors":"Gottschalk, Christopher; Buse, Dawn C; Marmura, Michael J; Torphy, Bradley; Pavlovic, Jelena M; Dumas, Paula K; Lalvani, Nim; Blumenfeld, Andrew","year":2022,"journal":"Therapeutic advances in neurological disorders, 15, 17562864221095902","doi":"10.1177/17562864221095902","pmid":"35662957","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"All five approved migraine preventive treatments demonstrated clinically relevant benefits during the first treatment week:\n\n- Erenumab reduced weekly migraine days within 1 week (3 studies)\n- Fremanezumab increased headache-free days starting Day 1 and significantly reduced migraine frequency within 1 week (6 studies)\n- Galcanezumab significantly reduced the number of patients experiencing migraine beginning Day 1 and through the first week (3 studies)\n- Eptinezumab reduced migraine attack likelihood on Day 1 by more than 50% versus baseline (4 studies)\n- OnabotulinumtoxinA reduced headache and migraine days within 1 week (2 studies)\n\nFour publications also reported improvements in function, disability, and quality of life as early as Week 4. No publications on traditional oral preventive agents met the criteria for early-onset prevention.","whyItMatters":"Migraine patients often endure weeks or months waiting for traditional preventive medications to take effect, during which they continue to suffer attacks and may lose faith in treatment. Demonstrating that newer peptide-targeted therapies work within days rather than weeks supports earlier adoption of these treatments and could improve patient adherence and quality of life.","specificNumbers":"","methodology":"This was an evidence-based scoping literature review searching PubMed, EMBASE, and CINAHL for clinical trial publications between 1988 and 2020. The review focused on approved migraine preventive treatments demonstrating benefits within 30 days of administration. A total of 16 publications describing 18 studies were identified and analyzed.","limitations":"The review only identified studies on five approved treatments; no publications on traditional oral preventives met the inclusion criteria, making direct comparison impossible. Cost-benefit analyses were absent from all included studies. The scoping review methodology is less rigorous than a systematic review. The search was limited to publications through 2020, missing more recent data."},{"rthcId":"RPEP-06155","title":"Emerging evidence of the relationship between fat-free mass and ghrelin, glucagon-like peptide-1, and peptide-YY.","authors":"Graybeal, Austin J; Willis, Jada L; Morales-Marroquin, Elisa; Tinsley, Grant M; Messiah, Sarah E; Shah, Meena","year":2022,"journal":"Nutrition (Burbank, Los Angeles County, Calif.), 103-104, 111815","doi":"10.1016/j.nut.2022.111815","pmid":"36088864","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Ghrelin has an inverse relationship with fat-free mass, but effects on other hormones are unclear.","whyItMatters":"Understanding how fat-free mass influences appetite hormones could improve weight management strategies. This knowledge may help in developing better approaches for appetite control during weight loss.","specificNumbers":"","methodology":"This study is a review of existing literature on fat-free mass and appetite hormones.","limitations":"The review primarily summarizes existing studies without new experimental data, limiting direct conclusions."},{"rthcId":"RPEP-06156","title":"Potentiation of endocannabinoids and other lipid amides prevents hyperalgesia and inflammation in a pre-clinical model of migraine.","authors":"Greco, Rosaria; Demartini, Chiara; Zanaboni, Anna Maria; Francavilla, Miriam; Reggiani, Angelo; Realini, Natalia; Scarpelli, Rita; Piomelli, Daniele; Tassorelli, Cristina","year":2022,"journal":"The journal of headache and pain, 23(1), 79","doi":"10.1186/s10194-022-01449-1","pmid":"35799128","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"ARN14633 and ARN14280 reduced pain behaviors and inflammatory markers in a rat model of migraine.","whyItMatters":"These findings highlight a potential new approach for treating migraines by targeting the FAAH enzyme. If successful in humans, it could lead to better pain management options.","specificNumbers":"","methodology":"The study used a migraine-specific rat model, administering the compounds after inducing hyperalgesia with nitroglycerin.","limitations":"The study was conducted in rats, so results may not directly translate to humans. Further research is needed to understand the mechanisms involved."},{"rthcId":"RPEP-06157","title":"Efficacy and safety of tirzepatide in patients with type 2 diabetes mellitus: A bayesian network meta-analysis.","authors":"Guan, Ruifang; Yang, Qing; Yang, Xiaolei; Du, Wandi; Li, Xuening; Ma, Guo","year":2022,"journal":"Frontiers in pharmacology, 13, 998816","doi":"10.3389/fphar.2022.998816","pmid":"36313305","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tirzepatide 15 mg reduced glycated hemoglobin by 93.5% and body weight by 99.7% compared to insulin.","whyItMatters":"These findings suggest that tirzepatide could be a more effective option for managing type 2 diabetes, potentially improving patient outcomes. Understanding its safety profile is crucial for healthcare providers.","specificNumbers":"","methodology":"The study utilized a Bayesian network meta-analysis of randomized controlled trials (RCTs) to compare tirzepatide with other diabetes treatments.","limitations":"The study calls for more well-designed RCTs to further evaluate tirzepatide's clinical performance and its cardiovascular benefits."},{"rthcId":"RPEP-06158","title":"Assessment of Exenatide loaded Biotinylated Trimethylated Chitosan/HP- 55 Nanoparticles.","authors":"Guo, Hejian; Yan, Xuehui; Tang, Hao; Zhang, Xiaoyan","year":2022,"journal":"Current drug delivery, 19(1), 32-40","doi":"10.2174/1567201818666210614100603","pmid":"34126896","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The relative pharmacological bioavailability of biotin modified nanoparticles was 1.27-fold higher than unmodified ones.","whyItMatters":"Improving the oral delivery of exenatide could significantly enhance patient compliance and comfort. This research may pave the way for new oral formulations of other difficult-to-administer drugs.","specificNumbers":"","methodology":"The study involved synthesizing biotinylated trimethylated chitosan nanoparticles, characterizing their structure, and testing their drug release and antidiabetic effects in diabetic mice.","limitations":"The study was conducted in diabetic mice, and further research is needed to confirm the findings in humans."},{"rthcId":"RPEP-06159","title":"Modification Strategies for Ionic Complementary Self-Assembling Peptides: Taking RADA16-I as an Example.","authors":"Guo, Weiwei; Ma, Yinping; Hu, Lei; Feng, Yujie; Liu, Yanmiao; Yi, Xuedong; Zhang, Wenzhi; Tang, Fushan","year":2022,"journal":"Polymers, 14(23)","doi":"10.3390/polym14235221","pmid":"36501615","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Modifications can improve RADA16-I's specific activity and mechanical properties.","whyItMatters":"Enhancing RADA16-I could lead to better applications in drug delivery and biomaterials. This research may pave the way for more effective therapeutic solutions.","specificNumbers":"","methodology":"The study is a review of existing modification strategies for RADA16-I.","limitations":"As a review, it does not present new experimental data or direct clinical trials."},{"rthcId":"RPEP-06160","title":"Guanidinium-Functionalized Flexible Azaproline Transporter for Efficient Intracellular Delivery of Proapoptotic Peptide and PDL1 Antisense Morpholino Oligo in Human Carcinoma Cells In Vitro.","authors":"Gupta, Abhishek; Gupta, Shalini; Das, Ujjal; Sinha, Surajit","year":2022,"journal":"Bioconjugate chemistry, 33(5), 907-917","doi":"10.1021/acs.bioconjchem.2c00129","pmid":"35486710","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The researchers synthesized a flexible azaproline-tetraguanidinium transporter (FAT) that uses a non-natural peptide backbone incorporating δ-azaproline residues. This backbone provides proteolytic stability, addressing a key weakness of natural cell-penetrating peptides.\n\nFAT adopted a random-coil structure rather than the typical polyproline helix and entered CHO cells via direct translocation. When conjugated with a proapoptotic domain peptide (14-mer) and a PDL1 morpholino antisense oligo (25-mer), FAT successfully delivered both into human carcinoma cells. Efficacy was confirmed by MTT assay (cell viability) and western blot (protein knockdown), respectively.","whyItMatters":"Drug delivery remains one of the biggest challenges in cancer therapy — many promising molecules cannot cross cell membranes effectively. This study introduces a proteolytically stable alternative to natural cell-penetrating peptides that could improve the intracellular delivery of peptide drugs and antisense therapeutics, potentially making cancer treatments more effective.","specificNumbers":"","methodology":"The team synthesized the FAT transporter using a revised scalable methodology for δ-azaproline. They characterized its structure using CD spectroscopy, studied cellular uptake in CHO cells using a Bodipy fluorophore conjugate, and tested delivery of two therapeutic cargos in human carcinoma cells using MTT assays and western blot analysis.","limitations":"This study was conducted entirely in vitro using cell lines, so it remains unknown whether FAT would perform similarly in living organisms. In vivo challenges such as biodistribution, toxicity, immune response, and pharmacokinetics were not addressed. The study also did not compare FAT's performance quantitatively against established cell-penetrating peptides."},{"rthcId":"RPEP-06161","title":"Therapeutic potential of GHSR-1A antagonism in alcohol dependence, a review.","authors":"Gupta, Shreyasi; Mukhopadhyay, Sanchari; Mitra, Arkadeep","year":2022,"journal":"Life sciences, 291, 120316","doi":"10.1016/j.lfs.2022.120316","pmid":"35016882","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review found that acylated ghrelin levels positively correlate with alcohol-induced brain responses in the ventral striatum — a key reward processing area — in both the right and left hemispheres. This suggests ghrelin signaling directly amplifies the brain's reward response to alcohol.\n\nGHSR-1A antagonism has been shown in preclinical and early clinical studies to suppress artificial reward circuitries and promote self-control for alcohol consumption. Notably, GHSR-1A also exhibits ligand-independent constitutive activity, meaning it can activate reward pathways even without ghrelin binding — which may explain why some people experience persistent cravings.","whyItMatters":"Alcohol use disorder affects hundreds of millions of people globally, yet existing treatments have limited effectiveness and high relapse rates. The ghrelin system represents an entirely different therapeutic target — one that addresses the neurological reward mechanisms driving addiction rather than just managing withdrawal symptoms. If GHSR-1A antagonists prove effective in clinical trials, they could offer a fundamentally new approach to addiction medicine.","specificNumbers":"","methodology":"The authors conducted an updated narrative review of recent preclinical, clinical, and experimental data examining the ghrelin-GHSR-1A signaling pathway in the context of alcohol use disorder. They focused on functional and molecular mechanisms of central ghrelin signaling at different levels of alcohol craving.","limitations":"This is a narrative review that synthesizes existing preclinical and clinical data without conducting new experiments. Most evidence for GHSR-1A antagonism in alcohol dependence comes from animal models, with limited human clinical data available. The complex neuro-psycho-endocrinological nature of alcohol use disorder means that targeting a single receptor pathway may have limited standalone efficacy. Translation from preclinical findings to effective human therapies remains unproven."},{"rthcId":"RPEP-06162","title":"Immunomodulatory and Allergenic Properties of Antimicrobial Peptides.","authors":"Guryanova, Svetlana V; Ovchinnikova, Tatiana V","year":2022,"journal":"International journal of molecular sciences, 23(5)","doi":"10.3390/ijms23052499","pmid":"35269641","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"AMPs enhance antigen-specific immunity and can activate adaptive immunity.","whyItMatters":"As antibiotic resistance rises, AMPs offer a potential alternative for infection treatment, but their safety and efficacy need thorough investigation.","specificNumbers":"","methodology":"The study is a review summarizing current knowledge on the immunomodulatory effects of AMPs.","limitations":"The review highlights the allergenic properties and cytostatic activity of AMPs against normal cells, which may limit their medical use."},{"rthcId":"RPEP-06163","title":"The Two Domains of the Avian Double-β-Defensin AvBD11 Have Different Ancestors, Common with Potential Monodomain Crocodile and Turtle Defensins.","authors":"Guyot, Nicolas; Landon, Céline; Monget, Philippe","year":2022,"journal":"Biology, 11(5)","doi":"10.3390/biology11050690","pmid":"35625418","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"AvBD11's two domains have different ancestral origins and share common ancestry with crocodile and turtle defensins.","whyItMatters":"Understanding the evolution of defensins can provide insights into the immune systems of vertebrates and their adaptability. This research may also shed light on the evolutionary relationships between birds and reptiles.","specificNumbers":"","methodology":"The study employed phylogenetic analysis to compare the protein sequences of AvBD11 across various bird species.","limitations":"The study focuses on phylogenetic analysis, which may not capture all aspects of functional evolution in defensins."},{"rthcId":"RPEP-06164","title":"Analysis of Macrophages and Peptidergic Fibers in the Skin of Patients With Painful Diabetic Polyneuropathy.","authors":"Gylfadottir, Sandra Sif; Itani, Mustapha; Kristensen, Alexander Gramm; Tankisi, Hatice; Jensen, Troels Staehelin; Sindrup, Søren H; Bennett, David LH; Nyengaard, Jens Randel; Finnerup, Nanna Brix; Karlsson, Pall","year":2022,"journal":"Neurology(R) neuroimmunology & neuroinflammation, 9(1)","doi":"10.1212/NXI.0000000000001111","pmid":"34764216","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Patients with P-DPN had 8.0% macrophage density and higher neuropeptide levels compared to NP-DPN.","whyItMatters":"Understanding the immune response in painful diabetic neuropathy could lead to new treatment strategies. This research highlights the potential role of inflammation in neuropathic pain.","specificNumbers":"","methodology":"The study involved skin biopsies from 60 diabetic patients (30 with P-DPN and 30 with NP-DPN) and 30 healthy controls, analyzed for macrophage and neuropeptide markers.","limitations":"The study did not measure markers of activated macrophages, which could provide more insight into their role in pain."},{"rthcId":"RPEP-06165","title":"Synthetic Peptides in Doping Control: A Powerful Tool for an Analytical Challenge.","authors":"Gómez-Guerrero, Néstor Alejandro; González-López, Nicolás Mateo; Zapata-Velásquez, Juan Diego; Martínez-Ramírez, Jorge Ariel; Rivera-Monroy, Zuly Jenny; García-Castañeda, Javier Eduardo","year":2022,"journal":"ACS omega, 7(43), 38193-38206","doi":"10.1021/acsomega.2c05296","pmid":"36340120","tags":["doping-detection","peptide-analysis","anti-doping"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Detecting peptide doping is one of the hardest challenges in anti-doping science because many performance-enhancing peptides have extremely short half-lives and are identical or nearly identical to natural hormones. This review covers the analytical strategies used to detect banned peptides from WADA sections S2 (peptide hormones and growth factors), S4 (hormone and metabolic modulators), and S5 (diuretics and masking agents).\n\nThe key detection tools include solid-phase peptide synthesis (SPPS) to create reference standards and isotopically labeled analogs for quantification, combined with liquid chromatography-high resolution mass spectrometry (LC-HRMS) for analysis in biological samples like blood and urine.","whyItMatters":"Peptide doping is widespread in sports but notoriously difficult to detect. Many banned peptides (GH secretagogues, EPO mimetics, IGF-1 analogs) clear the body in hours and look almost identical to natural hormones. This review consolidates the state of the art in detection methodology, which is critical as more peptides appear on the WADA banned list and athletes continue to seek performance-enhancing substances that evade testing.","specificNumbers":"WADA sections S2, S4, S5 · LC-HRMS primary detection technique · SPPS for reference materials · SPE and protein precipitation for sample preparation","methodology":"Comprehensive narrative review of the analytical chemistry behind peptide doping detection, covering synthetic reference material production, biological sample preparation methods, and instrumentation for peptide detection in complex biological matrices.","limitations":"This is a methodological review focused on analytical techniques, not a study of doping prevalence or athlete outcomes. Detection sensitivity varies greatly between peptide types, and the review notes that many peptides still lack validated detection methods. The rapid pace of novel peptide development means detection methods quickly become outdated."},{"rthcId":"RPEP-06166","title":"Estrogen differentially regulates transcriptional landscapes of preoptic and arcuate kisspeptin neuron populations.","authors":"Göcz, Balázs; Takács, Szabolcs; Skrapits, Katalin; Rumpler, Éva; Solymosi, Norbert; Póliska, Szilárd; Colledge, William H; Hrabovszky, Erik; Sárvári, Miklós","year":2022,"journal":"Frontiers in endocrinology, 13, 960769","doi":"10.3389/fendo.2022.960769","pmid":"36093104","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"222 E2-dependent genes were identified in KPRP3V neurons, while 1583 E2-induced changes were found in KPARC neurons.","whyItMatters":"Understanding how estrogen regulates these neurons can provide insights into reproductive health and hormonal feedback mechanisms. This knowledge could lead to better treatments for hormone-related disorders.","specificNumbers":"","methodology":"Transgenic mice were ovariectomized and treated with estrogen or a vehicle, followed by RNA sequencing of laser-captured kisspeptin neurons.","limitations":"The study was conducted in mice, and results may not directly translate to humans. Additionally, the complexity of the transcriptional mechanisms requires further exploration."},{"rthcId":"RPEP-06167","title":"Hazelnut peptide fractions preserve their bioactivities beyond industrial manufacture and simulated digestion of hazelnut cocoa cream.","authors":"Göksu, Ayşe Gülden; Çakır, Bilal; Gülseren, İbrahim","year":2022,"journal":"Food research international (Ottawa, Ont.), 161, 111865","doi":"10.1016/j.foodres.2022.111865","pmid":"36192905","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Bioactive attributes in hazelnut cocoa cream showed ACE-inhibitory activity up to 92% and antidiabetic activity between 7.5% and 44.4%.","whyItMatters":"These findings highlight the potential of hazelnut peptides in food products, offering health benefits while reducing allergenicity. This could lead to healthier food options for consumers.","specificNumbers":"","methodology":"The study involved using bioactive hazelnut protein hydrolysates in cocoa cream production and assessing their stability through processing and simulated digestion.","limitations":"The study was conducted in vitro, so results may not fully translate to human digestion and health outcomes."},{"rthcId":"RPEP-06168","title":"Upregulated expression of substance P and NK1R in blood monocytes and B cells of patients with allergic rhinitis and asthma.","authors":"Han, Peixuan; Chen, Liping; Chen, Dong; Yang, Ruiming; Wang, Wei; Liu, Jingyu; He, Shaoheng; Zhang, Huiyun","year":2022,"journal":"Clinical and experimental immunology, 210(1), 39-52","doi":"10.1093/cei/uxac074","pmid":"36001730","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"SP+ monocytes and B cells were elevated in allergic rhinitis and asthma patients, with NK1R+ monocytes also increased.","whyItMatters":"Understanding the role of SP and NK1R in allergic conditions could lead to new therapeutic targets for treating allergic rhinitis and asthma.","specificNumbers":"","methodology":"The study used flow cytometry to analyze blood samples from patients and mouse models of allergic rhinitis and asthma.","limitations":"The study primarily focuses on blood cells and may not fully represent the complex immune responses in allergic conditions."},{"rthcId":"RPEP-06169","title":"Efficacy and safety of setmelanotide, a melanocortin-4 receptor agonist, in patients with Bardet-Biedl syndrome and Alström syndrome: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial with an open-label period.","authors":"Haqq, Andrea M; Chung, Wendy K; Dollfus, Hélène; Haws, Robert M; Martos-Moreno, Gabriel Á; Poitou, Christine; Yanovski, Jack A; Mittleman, Robert S; Yuan, Guojun; Forsythe, Elizabeth; Clément, Karine; Argente, Jesús","year":2022,"journal":"The lancet. Diabetes & endocrinology, 10(12), 859-868","doi":"10.1016/S2213-8587(22)00277-7","pmid":"36356613","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06170","title":"Teduglutide in short bowel syndrome patients: A way back to normal life?","authors":"Harpain, Felix; Schlager, Lukas; Hütterer, Elisabeth; Dawoud, Christopher; Kirchnawy, Sabine; Stift, Judith; Krotka, Pavla; Stift, Anton","year":2022,"journal":"JPEN. Journal of parenteral and enteral nutrition, 46(2), 300-309","doi":"10.1002/jpen.2272","pmid":"34614239","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"All 13 patients (100%) showed a clinically significant reduction in parenteral support volume.","whyItMatters":"This research highlights the potential of teduglutide to improve the quality of life for patients with short bowel syndrome, reducing reliance on parenteral nutrition.","specificNumbers":"","methodology":"A retrospective analysis of 13 patients treated with teduglutide in a specialized program over four years.","limitations":"The study is limited by its small sample size and retrospective design, which may affect the generalizability of the findings."},{"rthcId":"RPEP-06171","title":"Selective G protein signaling driven by substance P-neurokinin receptor dynamics.","authors":"Harris, Julian A; Faust, Bryan; Gondin, Arisbel B; Dämgen, Marc André; Suomivuori, Carl-Mikael; Veldhuis, Nicholas A; Cheng, Yifan; Dror, Ron O; Thal, David M; Manglik, Aashish","year":2022,"journal":"Nature chemical biology, 18(1), 109-115","doi":"10.1038/s41589-021-00890-8","pmid":"34711980","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Substance P requires specific interactions with NK1R to activate Gs signaling, while SP6-11 leads to Gq signaling.","whyItMatters":"Understanding how different peptides interact with receptors can lead to more effective pain management strategies. This research may inform the development of drugs that selectively target specific signaling pathways.","specificNumbers":"","methodology":"The study utilized cryogenic-electron microscopy and molecular dynamics simulations to analyze NK1R structures and interactions with peptides.","limitations":"The study primarily focuses on receptor dynamics in vitro, which may not fully replicate in vivo conditions."},{"rthcId":"RPEP-06172","title":"The evolution of PRRT for the treatment of neuroendocrine tumors; What comes next?","authors":"Harris, Philip E; Zhernosekov, Konstantin","year":2022,"journal":"Frontiers in endocrinology, 13, 941832","doi":"10.3389/fendo.2022.941832","pmid":"36387893","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Lu-177-DOTATATE showed a median progression-free survival of 28.4 months compared to 8.5 months for octreotide LAR.","whyItMatters":"These advancements in PRRT could significantly improve treatment outcomes for patients with neuroendocrine tumors, offering new hope for better management of the disease.","specificNumbers":"","methodology":"The study reviews clinical trials and ongoing research comparing different treatment approaches for NETs.","limitations":"The study primarily reviews existing data and ongoing trials, lacking direct experimental results from new therapies."},{"rthcId":"RPEP-06173","title":"Inhibition of FOXP3 by stapled alpha-helical peptides dampens regulatory T cell function.","authors":"Hawley, Katrina M; Eclov, Rachel J; Schnorenberg, Mathew R; Tian, Yu; Shah, Rhea N; Thomas-Toth, Anika T; Fefferman, Marie; Bird, Gregory H; Walensky, Loren D; Tirrell, Matthew V; LaBelle, James L","year":2022,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 119(42), e2209044119","doi":"10.1073/pnas.2209044119","pmid":"36227917","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Lead SAH-FOXP3 peptides impeded Treg cell function and altered gene expression in vivo.","whyItMatters":"This research could pave the way for new therapies that enhance immune responses in conditions like cancer, where Treg cells inhibit effective treatment.","specificNumbers":"","methodology":"The study involved designing and synthesizing stapled peptides to block FOXP3 interactions, followed by biochemical evaluations and in vivo testing.","limitations":"The study primarily focuses on peptide design and in vitro/in vivo models, which may not fully translate to human applications."},{"rthcId":"RPEP-06174","title":"Identification of Bioactive Peptides from Nannochloropsis oculata Using a Combination of Enzymatic Treatment, in Silico Analysis and Chemical Synthesis.","authors":"Hayes, Maria; Mora, Leticia; Lucakova, Simona","year":2022,"journal":"Biomolecules, 12(12)","doi":"10.3390/biom12121806","pmid":"36551234","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The ACE-1 IC50 value for the permeate fraction was 370 µg/mL.","whyItMatters":"The identification of bioactive peptides from microalgae could lead to new functional foods that promote health. This research opens avenues for using natural resources in dietary supplements.","specificNumbers":"","methodology":"The study involved protein isolation through ammonium salt precipitation and xylanase treatment, followed by mass spectrometry analysis.","limitations":"The study was conducted in vitro, so results may not directly translate to human health outcomes."},{"rthcId":"RPEP-06175","title":"Pharmacokinetics, distribution, metabolism, and excretion of body-protective compound 157, a potential drug for treating various wounds, in rats and dogs.","authors":"He, Lei; Feng, Donglin; Guo, Hui; Zhou, Yueyuan; Li, Zhaozhao; Zhang, Kuo; Zhang, Wangqian; Wang, Shuning; Wang, Zhaowei; Hao, Qiang; Zhang, Cun; Gao, Yuan; Gu, Jintao; Zhang, Yingqi; Li, Weina; Li, Meng","year":2022,"journal":"Frontiers in pharmacology, 13, 1026182","doi":"10.3389/fphar.2022.1026182","pmid":"36588717","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"After single intravenous and intramuscular administration, BPC-157 showed a very short elimination half-life of less than 30 minutes in both rats and beagle dogs. Pharmacokinetics were linear across all tested doses. Mean absolute bioavailability after intramuscular injection was approximately 14-19% in rats and 45-51% in beagle dogs.\n\nUsing tritium-labeled ([³H]) BPC-157, the researchers tracked the peptide's fate in the body. It was rapidly metabolized into small peptide fragments that were further broken down into individual amino acids entering normal metabolic pathways. The primary excretion routes were urine and bile. These findings represent the first comprehensive pharmacokinetic characterization of BPC-157.","whyItMatters":"BPC-157 has been studied extensively in animal models for wound healing and tissue protection, but pharmacokinetic data — how the drug behaves in the body — is a prerequisite for human clinical trials. This study fills a critical gap by providing the first formal PK profile, showing the peptide's absorption, metabolism, and elimination characteristics. The short half-life and rapid metabolism explain why BPC-157 may need frequent dosing and inform future clinical trial design.","specificNumbers":"","methodology":"Researchers administered synthesized BPC-157 to rats and beagle dogs via single intravenous injection, single intramuscular injection at three escalating doses, and repeated intramuscular injections. Blood samples were collected at multiple time points to measure BPC-157 concentrations and calculate pharmacokinetic parameters. Tritium-labeled ([³H]) BPC-157 was used to track distribution, metabolism, and excretion pathways. Metabolites were identified in various tissues and excreta.","limitations":"The study was conducted only in rats and dogs — pharmacokinetic parameters can differ significantly in humans. The intramuscular route was studied but oral and subcutaneous routes (commonly used by peptide consumers) were not characterized. The short half-life raises questions about how often BPC-157 would need to be dosed to maintain therapeutic levels. While the PK data is valuable, it does not address efficacy or safety in humans."},{"rthcId":"RPEP-06176","title":"Association of Glucagon-Like Peptide-1 Receptor Agonist Use With Risk of Gallbladder and Biliary Diseases: A Systematic Review and Meta-analysis of Randomized Clinical Trials.","authors":"He, Liyun; Wang, Jialu; Ping, Fan; Yang, Na; Huang, Jingyue; Li, Yuxiu; Xu, Lingling; Li, Wei; Zhang, Huabing","year":2022,"journal":"JAMA internal medicine, 182(5), 513-519","doi":"10.1001/jamainternmed.2022.0338","pmid":"35344001","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RA treatment was associated with a 37% increased risk of gallbladder or biliary diseases (RR, 1.37).","whyItMatters":"Understanding the risks associated with GLP-1 receptor agonists is crucial for patient safety, especially as these drugs are increasingly used for weight loss and diabetes management.","specificNumbers":"","methodology":"The study conducted a systematic review and meta-analysis of 76 randomized clinical trials comparing GLP-1 RAs to placebo or non-GLP-1 RAs.","limitations":"The study is limited to data from randomized trials, which may not capture all real-world scenarios and long-term effects."},{"rthcId":"RPEP-06177","title":"Dipeptidyl peptidase-4 inhibitors and gallbladder or biliary disease in type 2 diabetes: systematic review and pairwise and network meta-analysis of randomised controlled trials.","authors":"He, Liyun; Wang, Jialu; Ping, Fan; Yang, Na; Huang, Jingyue; Li, Wei; Xu, Lingling; Zhang, Huabing; Li, Yuxiu","year":2022,"journal":"BMJ (Clinical research ed.), 377, e068882","doi":"10.1136/bmj-2021-068882","pmid":"35764326","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Dipeptidyl peptidase-4 inhibitors increased the risk of gallbladder diseases (OR 1.22) and cholecystitis (OR 1.43).","whyItMatters":"Understanding the risks associated with diabetes medications is crucial for patient safety and treatment decisions. This study highlights the need for careful monitoring of patients on dipeptidyl peptidase-4 inhibitors.","specificNumbers":"","methodology":"The study conducted a systematic review and meta-analysis of randomized controlled trials involving adults with type 2 diabetes.","limitations":"The study may not account for all confounding factors, and the results may not generalize to all populations."},{"rthcId":"RPEP-06178","title":"Turing milk into pro-apoptotic oral nanotherapeutic: De novo bionic chiral-peptide supramolecule for cancer targeted and immunological therapy.","authors":"He, Wangxiao; Zhang, Zhang; Yang, Wenguang; Zheng, Xiaoqiang; You, Weiming; Yao, Yu; Yan, Jin; Liu, Wenjia","year":2022,"journal":"Theranostics, 12(5), 2322-2334","doi":"10.7150/thno.70568","pmid":"35265212","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The chiral peptide supramolecule DPAICP@ME (D-peptide Au(I) infinite covalent polymer camouflaged with milk extracellular vesicle membranes) demonstrated:\n\n- Stability through gastrointestinal absorption and blood circulation after oral administration\n- Satisfactory tumor accumulation via oral medication\n- Restoration of p53 signaling pathway for cancer therapy\n- Efficacy across three cancer models: B16F10 melanoma homograft, LLC Lewis orthotopic lung cancer, and patient-derived orthotopic xenograft (PDOX) colon cancer\n- Enhancement of anti-PD1 immunotherapy through further T-cell activation when used in combination","whyItMatters":"Oral cancer therapy is a long-standing goal in oncology — it would dramatically improve patient quality of life and treatment compliance. This study overcomes two major barriers: peptide degradation in the gut (solved by using protease-resistant D-peptides) and poor absorption (solved by milk vesicle camouflage). The demonstration that an oral peptide nanomedicine can both directly kill cancer cells via p53 and enhance immunotherapy marks a significant advance in peptide-based cancer treatment.","specificNumbers":"","methodology":"The researchers synthesized a chiral peptide-gold supramolecular nanostructure through an aqueous growth method combining organothiol D-peptides with Au3+. This was then camouflaged with membranes from milk-derived extracellular vesicles. The nanoparticles were characterized for pharmaceutical properties and tested in vivo through oral administration in three mouse cancer models. Combination studies with anti-PD1 immunotherapy evaluated immune activation and T-cell responses.","limitations":"All studies were conducted in mouse models — pharmacokinetics, toxicity, and efficacy may differ significantly in humans. The complex multi-component nanostructure (D-peptide + gold + milk vesicle membranes) presents significant manufacturing and regulatory challenges. Long-term safety of gold-containing nanoparticles administered orally is not established. The specific tumor accumulation mechanism and efficiency after oral delivery would need detailed characterization in larger animals before clinical translation."},{"rthcId":"RPEP-06179","title":"Peptide-Based Cancer Vaccine Delivery via the STINGΔTM-cGAMP Complex.","authors":"He, Yanpu; Hong, Celestine; Fletcher, Samantha J; Berger, Adam G; Sun, Xin; Yang, Mengdi; Huang, Shengnan; Belcher, Angela M; Irvine, Darrell J; Li, Jiahe; Hammond, Paula T","year":2022,"journal":"Advanced healthcare materials, 11(15), e2200905","doi":"10.1002/adhm.202200905","pmid":"35670244","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The new delivery system improved T cell priming and antitumoral response in a mouse model.","whyItMatters":"Improving peptide vaccine delivery could significantly enhance cancer immunotherapy outcomes. This method addresses challenges in vaccine transport and immune activation.","specificNumbers":"","methodology":"The study involved creating a peptide-STINGΔTM-cGAMP complex and testing its effectiveness in vitro and in vivo using a mouse model.","limitations":"The study was conducted in mice, and results may not directly translate to humans."},{"rthcId":"RPEP-06180","title":"Blue Whiting (Micromesistius poutassou) Protein Hydrolysates Increase GLP-1 Secretion and Proglucagon Production in STC-1 Cells Whilst Maintaining Caco-2/HT29-MTX Co-Culture Integrity.","authors":"Heffernan, Shauna; Nunn, Leo; Harnedy-Rothwell, Pádraigín A; Gite, Snehal; Whooley, Jason; Giblin, Linda; FitzGerald, Richard J; O'Brien, Nora M","year":2022,"journal":"Marine drugs, 20(2)","doi":"10.3390/md20020112","pmid":"35200641","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Blue whiting protein hydrolysates increased GLP-1 secretion by 2.5 to 3.5 times compared to control.","whyItMatters":"Understanding how dietary proteins influence satiety hormones could help develop strategies to combat obesity. This research highlights the potential of fish proteins in appetite regulation.","specificNumbers":"","methodology":"The study involved testing various blue whiting protein hydrolysates on murine STC-1 cells to measure hormone secretion and production.","limitations":"The study was conducted in vitro, meaning results may not directly translate to human physiology."},{"rthcId":"RPEP-06181","title":"Swimming exercise versus L-carnosine supplementation for Alzheimer's dementia in rats: implication of circulating and hippocampal FNDC5/irisin.","authors":"Hegazy, Maha A; Abdelmonsif, Doaa A; Zeitoun, Teshreen M; El-Sayed, Norhan S; Samy, Doaa M","year":2022,"journal":"Journal of physiology and biochemistry, 78(1), 109-124","doi":"10.1007/s13105-021-00845-6","pmid":"35091983","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Both swimming and L-carnosine normalized hippocampal FNDC5/irisin expression and improved cognitive function.","whyItMatters":"These findings highlight potential non-drug interventions for Alzheimer's disease, which could be beneficial for cognitive health. Understanding how exercise and supplements like carnosine affect brain function may lead to new treatment strategies.","specificNumbers":"","methodology":"Rats were divided into groups receiving either swimming exercise or oral L-carnosine after being injected with a substance to induce memory impairment. After 5 weeks, their brain and blood samples were analyzed.","limitations":"The study was conducted in rats, which may limit the applicability of the findings to humans. Additionally, the long-term effects of these interventions were not assessed."},{"rthcId":"RPEP-06182","title":"Defensin-lipid interactions in membrane targeting: mechanisms of action and opportunities for the development of antimicrobial and anticancer therapeutics.","authors":"Hein, Matthew J A; Kvansakul, Marc; Lay, Fung T; Phan, Thanh Kha; Hulett, Mark D","year":2022,"journal":"Biochemical Society transactions, 50(1), 423-437","doi":"10.1042/BST20200884","pmid":"35015081","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Defensins uniquely target specific membrane lipids, offering potential for new therapies.","whyItMatters":"Defensins could provide a novel approach to treating infections and cancer, addressing issues of resistance seen with current therapies.","specificNumbers":"","methodology":"This is a review article summarizing recent research on defensins and their mechanisms.","limitations":"As a review, it does not present original experimental data and relies on existing studies."},{"rthcId":"RPEP-06183","title":"A COVID-19 peptide vaccine for the induction of SARS-CoV-2 T cell immunity.","authors":"Heitmann, Jonas S; Bilich, Tatjana; Tandler, Claudia; Nelde, Annika; Maringer, Yacine; Marconato, Maddalena; Reusch, Julia; Jäger, Simon; Denk, Monika; Richter, Marion; Anton, Leonard; Weber, Lisa Marie; Roerden, Malte; Bauer, Jens; Rieth, Jonas; Wacker, Marcel; Hörber, Sebastian; Peter, Andreas; Meisner, Christoph; Fischer, Imma; Löffler, Markus W; Karbach, Julia; Jäger, Elke; Klein, Reinhild; Rammensee, Hans-Georg; Salih, Helmut R; Walz, Juliane S","year":2022,"journal":"Nature, 601(7894), 617-622","doi":"10.1038/s41586-021-04232-5","pmid":"34814158","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06184","title":"Polypharmacological Cell-Penetrating Peptides from Venomous Marine Animals Based on Immunomodulating, Antimicrobial, and Anticancer Properties.","authors":"Hemmati, Shiva; Rasekhi Kazerooni, Haniyeh","year":2022,"journal":"Marine drugs, 20(12)","doi":"10.3390/md20120763","pmid":"36547910","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Identified 279 safe peptides with various therapeutic properties from 3,505 CPPs.","whyItMatters":"These findings could lead to new treatments for complex diseases that currently lack effective therapies. The multi-target approach of these peptides may enhance their clinical applicability.","specificNumbers":"","methodology":"The study involved the retrieval and analysis of peptides from marine animal toxins using omics technologies.","limitations":"The study primarily focuses on in vitro findings, which may not directly translate to clinical outcomes in humans."},{"rthcId":"RPEP-06185","title":"Translocating Peptides of Biomedical Interest Obtained from the Spike (S) Glycoprotein of the SARS-CoV-2.","authors":"Henao, Maria C; Ocasion, Camila; Puentes, Paola Ruiz; González-Melo, Cristina; Quezada, Valentina; Cifuentes, Javier; Yepes, Arnovis; Burgos, Juan C; Cruz, Juan C; Reyes, Luis H","year":2022,"journal":"Membranes, 12(6)","doi":"10.3390/membranes12060600","pmid":"35736307","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Peptide AHB-1 showed comparable penetration potential to known cell-penetrating peptides.","whyItMatters":"These findings could lead to improved methods for delivering therapies to cells, which is crucial in treating viral infections and other diseases.","specificNumbers":"","methodology":"The study used molecular dynamics simulations and in vitro analysis to assess peptide penetration and biocompatibility.","limitations":"The study primarily used simulations and in vitro models, which may not fully represent in vivo conditions."},{"rthcId":"RPEP-06186","title":"Neuropeptides, New Ligands of SARS-CoV-2 Nucleoprotein, a Potential Link between Replication, Inflammation and Neurotransmission.","authors":"Henri, Julien; Minder, Laetitia; Mohanasundaram, Kevin; Dilly, Sébastien; Goupil-Lamy, Anne; Di Primo, Carmelo; Slama Schwok, Anny","year":2022,"journal":"Molecules (Basel, Switzerland), 27(22)","doi":"10.3390/molecules27228094","pmid":"36432196","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Neuropeptides bind to SARS-CoV-2 nucleoprotein, inhibiting RNA binding and potentially reducing replication.","whyItMatters":"Understanding how neuropeptides interact with the SARS-CoV-2 nucleoprotein could provide insights into managing long COVID symptoms. Targeting these interactions may lead to new treatments.","specificNumbers":"","methodology":"The study used in silico screening and molecular dynamics simulations to identify ligands, followed by mutation studies and surface plasmon resonance experiments.","limitations":"The study primarily relies on in silico methods and may require further validation in biological systems."},{"rthcId":"RPEP-06187","title":"Vaccines for immunoprevention of DNA mismatch repair deficient cancers.","authors":"Hernandez-Sanchez, Alejandro; Grossman, Mark; Yeung, Kevin; Sei, Shizuko S; Lipkin, Steven; Kloor, Matthias","year":2022,"journal":"Journal for immunotherapy of cancer, 10(6)","doi":"10.1136/jitc-2021-004416","pmid":"35732349","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"DNA mismatch repair-deficient cancers produce a defined and predictable set of frameshift peptide neoantigens due to insertion/deletion mutations in coding microsatellites. These neoantigens are foreign to the immune system and can elicit strong CD8+ cytotoxic T cell responses.\n\nEvidence shows pre-existing immune surveillance against these neoantigens exists in Lynch syndrome carriers, suggesting the immune system already partially recognizes pre-cancerous cells. Three mechanisms of immune evasion allow cancers to escape this surveillance. A preventive vaccine could strengthen immune surveillance before evasion occurs. The review evaluates antigen selection and delivery strategies, concluding that RNA vaccines offer the most robust potential for immunoprevention.","whyItMatters":"Preventing cancer is fundamentally better than treating it. Lynch syndrome affects an estimated 1 in 279 people and carries up to 80% lifetime cancer risk. Because the neoantigens are predictable (unlike in most cancers), a single vaccine formulation could potentially protect all carriers — making this one of the most feasible preventive cancer vaccine approaches. Success here could establish a model for preventing other genetically defined cancers.","specificNumbers":"","methodology":"This is a comprehensive review article examining the pathogenesis of DNA mismatch repair-deficient cancers, evidence for immune surveillance, mechanisms of immune evasion, and the rationale for preventive vaccination. The authors review both preclinical studies and early clinical experience with frameshift peptide neoantigen-based vaccines, and evaluate antigen selection and delivery strategies.","limitations":"This is a review article presenting no new experimental data. The preventive vaccine concept, while scientifically compelling, has not been proven in large-scale human trials. Pre-existing immune surveillance in carriers suggests some natural protection already exists, and it's unclear how much additional benefit a vaccine would provide. The optimal antigen combination and delivery platform remain to be determined. Long-term safety of repeated neoantigen vaccination in healthy carriers needs evaluation."},{"rthcId":"RPEP-06188","title":"Optimization of the Rheological Properties of Self-Assembled Tripeptide/Alginate/Cellulose Hydrogels for 3D Printing.","authors":"Hernández-Sosa, Alejandro; Ramírez-Jiménez, Rosa Ana; Rojo, Luis; Boulmedais, Fouzia; Aguilar, María Rosa; Criado-Gonzalez, Miryam; Hernández, Rebeca","year":2022,"journal":"Polymers, 14(11)","doi":"10.3390/polym14112229","pmid":"35683902","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The addition of Fmoc-FFY peptide improved cell adhesion but slowed MG63 cell growth.","whyItMatters":"This research is significant as it enhances the materials used in 3D printing for tissue engineering, potentially leading to better scaffolds for regenerative medicine.","specificNumbers":"","methodology":"Different formulations of alginate and cellulose were tested to create printable inks, followed by 3D printing and characterization of the resulting scaffolds.","limitations":"The study primarily focused on one type of cell line (MG63) and may not represent all cell types' responses."},{"rthcId":"RPEP-06189","title":"Michaelis-Menten Quantification of Ligand Signaling Bias Applied to the Promiscuous Vasopressin V2 Receptor.","authors":"Heydenreich, Franziska Marie; Plouffe, Bianca; Rizk, Aurélien; Milić, Dalibor; Zhou, Joris; Breton, Billy; Le Gouill, Christian; Inoue, Asuka; Bouvier, Michel; Veprintsev, Dmitry B","year":2022,"journal":"Molecular pharmacology, 102(3), 139-149","doi":"10.1124/molpharm.122.000497","pmid":"35779859","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The Michaelis-Menten model accurately quantified ligand efficacies, revealing V2R's engagement with multiple G proteins.","whyItMatters":"Understanding how ligands activate receptors can lead to better drug development and more targeted therapies. This research provides a clearer framework for evaluating ligand efficacy.","specificNumbers":"","methodology":"The study employed BRET-based biosensors to measure G protein activation and compared traditional operational models with the new Michaelis-Menten approach.","limitations":"The study primarily focuses on a single receptor type and may not fully represent the complexities of other receptors."},{"rthcId":"RPEP-06190","title":"Endogenous opioid systems alterations in pain and opioid use disorder.","authors":"Higginbotham, Jessica A; Markovic, Tamara; Massaly, Nicolas; Morón, Jose A","year":2022,"journal":"Frontiers in systems neuroscience, 16, 1014768","doi":"10.3389/fnsys.2022.1014768","pmid":"36341476","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review maps the four endogenous opioid peptide systems and their roles:\n\n1. μ-opioid receptor (MOPR) / β-endorphins — primary mediator of pain relief and euphoria; the main target of opioid drugs\n2. κ-opioid receptor (KOPR) / dynorphins — involved in stress responses and dysphoria; may contribute to negative emotional states during withdrawal\n3. δ-opioid receptor (DOPR) / enkephalins — modulates mood, motivation, and pain; potential target for non-addictive analgesics\n4. Nociceptin receptor (NOPR) / nociceptins — regulates pain sensitivity, anxiety, and stress responses\n\nKey insight: chronic pain itself alters endogenous opioid system function, and these alterations — combined with the effects of exogenous opioid use — create a self-reinforcing cycle that increases the likelihood of developing opioid use disorder.","whyItMatters":"The opioid crisis has killed hundreds of thousands of people, yet pain management remains a critical medical need. The endogenous opioid peptides represent the body's own sophisticated pain management system — understanding exactly how chronic pain and opioid drugs disrupt these systems could reveal safer therapeutic strategies. For example, targeting the δ-opioid receptor with enkephalin-like drugs might provide pain relief without the euphoria and addiction risk associated with μ-receptor targeting drugs.","specificNumbers":"","methodology":"This is a comprehensive narrative review synthesizing decades of research on endogenous opioid peptide function, expression, pharmacology, and regulation. It covers basic science, animal models, and clinical observations on pain, opioid use, and addiction.","limitations":"As a narrative review, it does not present original experimental data or systematic methodology. The endogenous opioid literature is vast, and the review necessarily simplifies some aspects. The relationship between endogenous opioid system alterations and OUD development is supported by strong evidence but establishing direct causation in humans remains challenging. Individual genetic variation in opioid receptor expression and function adds complexity not fully addressed."},{"rthcId":"RPEP-06191","title":"Peptide functionalized DNA hydrogel enhances neuroblastoma cell growth and differentiation.","authors":"Hivare, Pravin; Gangrade, Ankit; Swarup, Gitanjali; Bhavsar, Krishna; Singh, Ankur; Gupta, Ratnika; Thareja, Prachi; Gupta, Sharad; Bhatia, Dhiraj","year":2022,"journal":"Nanoscale, 14(24), 8611-8620","doi":"10.1039/d1nr07187d","pmid":"35687044","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Peptide-modified DNA hydrogels resulted in enhanced neuronal differentiation and prolonged neurite length.","whyItMatters":"This research highlights the potential of peptide-modified biomaterials in tissue engineering, particularly for nerve regeneration. It could lead to new treatments for nerve injuries.","specificNumbers":"","methodology":"The study involved coating a glass surface with a DNA hydrogel and chemically linking it to a synthetic IKVAV peptide, followed by analysis of neuroblastoma stem cell behavior.","limitations":"The study primarily focuses on in vitro results, which may not fully translate to in vivo applications in humans."},{"rthcId":"RPEP-06192","title":"Peptide Receptor Radionuclide Therapy.","authors":"Hofland, Johannes; Brabander, Tessa; Verburg, Frederik A; Feelders, Richard A; de Herder, Wouter W","year":2022,"journal":"The Journal of clinical endocrinology and metabolism, 107(12), 3199-3208","doi":"10.1210/clinem/dgac574","pmid":"36198028","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"PRRT with 177Lu-DOTATATE (approved 2017-2018) is an established treatment for somatostatin receptor-positive well-differentiated neuroendocrine neoplasms (NENs):\n\n- Improves progression-free survival and quality of life in GEP NEN patients\n- Shows favorable symptomatic and biochemical responses in functioning metastatic tumors including insulinomas, VIPomas, glucagonomas, and gastrinomas\n- Being investigated as first-line therapy and in combination with cytotoxic drugs\n- Expanding to bronchopulmonary NENs, pheochromocytomas, paragangliomas, and medullary thyroid carcinomas\n\nNext-generation developments include somatostatin analog peptides coupled with alpha-emitting radionuclides (more potent radiation) and somatostatin receptor antagonists with radionuclides.","whyItMatters":"PRRT represents one of the most successful examples of peptide-based precision medicine — using a peptide's natural receptor-targeting ability to deliver radiation directly to cancer cells while sparing healthy tissue. Its 'theranostic' approach (same peptide for diagnosis and treatment) is a model for personalized cancer care.","specificNumbers":"","methodology":"This is a clinical review published in JCEM synthesizing published clinical trial data, approved indications, and emerging research on peptide receptor radionuclide therapy using radiolabeled somatostatin analogs.","limitations":"PRRT is currently approved only as second/third-line therapy, not first-line. Not all neuroendocrine tumors express sufficient somatostatin receptors for effective targeting. Side effects include renal toxicity and bone marrow suppression. Long-term outcomes beyond progression-free survival need further study. First-line use and combination therapy data are still preliminary."},{"rthcId":"RPEP-06193","title":"Epigenetic therapy in combination with a multi-epitope cancer vaccine targeting shared tumor antigens for high-risk myelodysplastic syndrome - a phase I clinical trial.","authors":"Holmberg-Thydén, Staffan; Dufva, Inge Høgh; Gang, Anne Ortved; Breinholt, Marie Fredslund; Schejbel, Lone; Andersen, Mette Klarskov; Kadivar, Mohammad; Svane, Inge Marie; Grønbæk, Kirsten; Hadrup, Sine Reker; El Fassi, Daniel","year":2022,"journal":"Cancer immunology, immunotherapy : CII, 71(2), 433-444","doi":"10.1007/s00262-021-02993-6","pmid":"34218294","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Five patients with high-risk MDS who had previously responded to azacitidine (AZA) monotherapy received a multi-peptide vaccine targeting NY-ESO-1, MAGE-A3, PRAME, and WT-1 antigens.\n\nResults were uniformly negative: no specific immune responses were detected by intracellular cytokine staining or ELISpot assays. Only minor changes in immune cell phenotype and marker expression were observed. All five patients progressed to acute myeloid leukemia (AML) with a mean time to progression of 5.2 months (range 2.8-7.6). Mean survival was 18.1 months from MDS diagnosis (range 10.9-30.6) and 11.3 months from study enrollment (range 4.3-22.2). Bone marrow sequencing revealed clonal expansion of malignant cells and emergence of novel mutations.","whyItMatters":"This was the first study to test whether epigenetic therapy (which unmasks hidden cancer targets) could synergize with a multi-peptide cancer vaccine in MDS. While the results were negative, they provide critical information: high-risk MDS patients may have immune systems too compromised to mount vaccine responses, even when tumor antigens are artificially upregulated. This shapes future research by highlighting the need for immune-restoring strategies before attempting vaccination in this population.","specificNumbers":"","methodology":"This was a phase I (safety and feasibility) clinical trial. Five patients with high-risk MDS who had responded to azacitidine monotherapy were enrolled. They received AZA combined with a therapeutic peptide vaccine targeting four shared tumor-associated antigens known to be upregulated by AZA treatment. Immune responses were monitored using intracellular cytokine staining and ELISpot assays. Immune cell phenotyping tracked changes in stimulatory and inhibitory markers. Bone marrow was sequenced to track clonal evolution. The trial was terminated early due to lack of clinical benefit.","limitations":"The major limitation is the extremely small sample size (n=5), which severely limits the ability to draw generalizable conclusions. There was no control group for comparison. All patients had high-risk MDS that may have been inherently resistant to immune-based approaches. The lack of immune response could reflect the specific peptide vaccine design, the patient population's immune status, or both. The early termination prevented assessment of whether longer treatment might have produced different results."},{"rthcId":"RPEP-06194","title":"A Novel Truncated Liver Enriched Antimicrobial Peptide-2 Palmitoylated at its N-Terminal Antagonizes Effects of Ghrelin.","authors":"Holá, Lucie; Železná, Blanka; Karnošová, Alena; Kuneš, Jaroslav; Fehrentz, Jean-Alain; Denoyelle, Séverine; Cantel, Sonia; Blechová, Miroslava; Sýkora, David; Myšková, Aneta; Maletínská, Lenka","year":2022,"journal":"The Journal of pharmacology and experimental therapeutics, 383(2), 129-136","doi":"10.1124/jpet.122.001322","pmid":"36198495","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Palmitoylated LEAP2(1-14) significantly reduced food intake and inhibited GH release, showing EC50 values in the 10-8 M range.","whyItMatters":"Understanding how LEAP2 interacts with ghrelin could lead to new treatments for obesity, a growing health concern worldwide.","specificNumbers":"","methodology":"The study involved testing various lipid-modified LEAP2 peptides for their binding affinity and anorexigenic effects in overnight fasted and free-fed mice.","limitations":"The study was conducted in mice, and results may not directly translate to humans. Further research is needed to confirm efficacy and safety."},{"rthcId":"RPEP-06195","title":"Characterization of proteolytic degradation products of vaginally administered bovine lactoferrin.","authors":"Hopp, Thomas P; Spiewak, Klaudyna; Matthews, Maura-Ann H; Athanasiou, Zafeiria; Blackmore, Richard S; Gelbfish, Gary A","year":2022,"journal":"PloS one, 17(5), e0268537","doi":"10.1371/journal.pone.0268537","pmid":"35587943","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Bovine lactoferrin degrades into fragments, primarily a 37 kDa N-lobe and a 43 kDa C-lobe, retaining iron-binding ability.","whyItMatters":"Understanding the degradation of bovine lactoferrin in vaginal fluid can inform its potential therapeutic applications and effectiveness. This knowledge may help in developing better formulations for vaginal health.","specificNumbers":"","methodology":"The study utilized clinical trials and ex vivo incubations, employing techniques like polyacrylamide gel electrophoresis and mass spectral analysis to characterize the degradation products.","limitations":"The study primarily focuses on bovine lactoferrin and may not directly translate to other proteins or human lactoferrin. Additionally, the variability in vaginal fluid composition among individuals could affect results."},{"rthcId":"RPEP-06196","title":"Intracellular delivery and photothermal therapeutic effects of polyhistidine peptide-modified gold nanoparticles.","authors":"Hori, Kosuke; Higashida, Shinichi; Osaki, Tomohiro; Kawano, Tsuyoshi; Inaba, Hiroshi; Matsuura, Kazunori; Iwasaki, Takashi","year":2022,"journal":"Journal of biotechnology, 354, 34-44","doi":"10.1016/j.jbiotec.2022.06.006","pmid":"35724765","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Polyhistidine peptide-modified AuNPs inhibited lung cancer cell proliferation under laser irradiation.","whyItMatters":"This research could improve the effectiveness of photothermal therapy for cancer by enhancing drug delivery to tumor cells. It highlights the potential of using peptide modifications to improve cancer treatment outcomes.","specificNumbers":"","methodology":"The study involved modifying gold nanoparticles with polyhistidine peptide and testing their internalization and therapeutic effects on lung cancer cells in vitro.","limitations":"The study was conducted in vitro, so results may not directly translate to human patients. Further research is needed to evaluate safety and effectiveness in vivo."},{"rthcId":"RPEP-06197","title":"Natriuretic Peptide-guided Therapy for Heart Failure.","authors":"Horiuchi, Yu; Villacorta, Humberto; Maisel, Alan S","year":2022,"journal":"Heart international, 16(2), 112-116","doi":"10.17925/HI.2022.16.2.112","pmid":"36741100","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The evidence for natriuretic peptide-guided therapy splits along several lines. In heart failure with reduced ejection fraction (HFrEF), the STARS-BNP and PROTECT trials demonstrated reduced cardiac events when medications were adjusted based on NP levels. Meta-analyses and the BATTLESCARRED and TIME-CHF studies showed mortality reduction specifically in patients under 75 years old.\n\nHowever, the PRIMA and GUIDE-IT trials found no significant differences between NP-guided and conventional care. In heart failure with preserved ejection fraction (HFpEF) and in acute heart failure settings, NP-guided therapy showed no benefit over standard care. A promising application is in prevention: NP levels may help identify people at risk of developing heart failure and guide early intervention.","whyItMatters":"Heart failure is one of the leading causes of hospitalization and death worldwide. Using objective biomarker measurements to fine-tune treatment — rather than waiting for symptoms to worsen — could potentially improve outcomes. Understanding where NP-guided therapy works (younger patients with reduced ejection fraction) and where it doesn't (preserved ejection fraction, acute settings) helps clinicians use this tool appropriately rather than applying it universally.","specificNumbers":"","methodology":"This is a narrative review article that synthesizes results from multiple randomized controlled trials and meta-analyses examining natriuretic peptide-guided therapy in heart failure. Key trials analyzed include STARS-BNP, PROTECT, BATTLESCARRED, TIME-CHF, PRIMA, and GUIDE-IT. The review compares outcomes across different heart failure subtypes (HFrEF vs HFpEF), clinical settings (chronic vs acute), and patient demographics (age stratification).","limitations":"This is a narrative review, not a systematic review or meta-analysis, so the study selection and interpretation may be subjective. The conflicting results across trials may reflect differences in NP targets, patient populations, medication protocols, and follow-up duration. The age-based benefit (under 75) identified in some studies may not generalize across all populations. The review focuses on BNP and NT-proBNP, not accounting for newer biomarkers that may complement NP-guided approaches."},{"rthcId":"RPEP-06198","title":"Cancer-specific T helper shared and neo-epitopes uncovered by expression of the MHC class II master regulator CIITA.","authors":"Hos, Brett J; Tondini, Elena; Camps, Marcel G M; Rademaker, Wesley; van den Bulk, Jitske; Ruano, Dina; Janssen, George M C; de Ru, Arnoud H; van den Elsen, Peter J; de Miranda, Noel F C C; van Veelen, Peter A; Ossendorp, Ferry","year":2022,"journal":"Cell reports, 41(2), 111485","doi":"10.1016/j.celrep.2022.111485","pmid":"36223747","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The study identified tumor-specific neo-epitopes and oncoviral epitopes that can stimulate CD4+ T cell responses.","whyItMatters":"Identifying specific T cell targets can enhance the development of personalized cancer immunotherapies. This method may improve treatment effectiveness by targeting unique tumor markers.","specificNumbers":"","methodology":"The researchers introduced CIITA into MHC class II negative tumor cells to enable peptide presentation and then used mass spectrometry to analyze the eluted peptides.","limitations":"The study primarily focuses on mouse models, and results may not directly translate to human applications."},{"rthcId":"RPEP-06199","title":"Protein Mimicry and the Design of Bioactive Cell-Penetrating Peptides: The Genesis of STOPSPERM Bioportides.","authors":"Howl, John; Silva, Joana Vieira; Fardilha, Margarida; Jones, Sarah","year":2022,"journal":"Methods in molecular biology (Clifton, N.J.), 2383, 293-306","doi":"10.1007/978-1-0716-1752-6_20","pmid":"34766298","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Bioportides improved sperm viability and motility, as assessed through specific protocols.","whyItMatters":"Understanding how these peptides work could lead to new fertility treatments. Enhancing sperm function may improve outcomes in assisted reproductive technologies.","specificNumbers":"","methodology":"The study utilized confocal microscopy to visualize peptide translocation and included protocols for assessing sperm viability and motility.","limitations":"The study primarily focuses on sperm cells in vitro, which may not fully translate to in vivo conditions."},{"rthcId":"RPEP-06200","title":"The effect of substance P and its common in vivo-formed metabolites on MRGPRX2 and human mast cell activation.","authors":"Hsin, Lin; Fernandopulle, Nithya A; Ding, Jie; Lumb, Chris; Veldhuis, Nicholas; Karas, John A; Northfield, Susan E; Mackay, Graham A","year":2022,"journal":"Pharmacology research & perspectives, 10(4), e00990","doi":"10.1002/prp2.990","pmid":"35904495","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"SP(1-9)-COOH activates MRGPRX2 but with reduced potency compared to intact SP.","whyItMatters":"Understanding how these peptides interact with mast cells could lead to new insights into inflammatory responses and potential therapeutic targets.","specificNumbers":"","methodology":"The study synthesized SP and its metabolites, then tested their effects on HEK293 cells and human mast cells in various assays.","limitations":"The study primarily focused on in vitro models, which may not fully represent in vivo conditions."},{"rthcId":"RPEP-06201","title":"VP4 Is a Determinant of Alpha-Defensin Modulation of Rotaviral Infection.","authors":"Hu, Ciara T; Diaz, Karina; Yang, Linda C; Sharma, Anjali; Greenberg, Harry B; Smith, Jason G","year":2022,"journal":"Journal of virology, 96(7), e0205321","doi":"10.1128/jvi.02053-21","pmid":"35285683","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Some rotaviruses have evolved resistance to alpha-defensins, while others remain sensitive.","whyItMatters":"Understanding how alpha-defensins interact with rotaviruses can inform vaccine development and improve our knowledge of viral evolution and transmission.","specificNumbers":"","methodology":"The study involved generating a panel of alpha-defensins from different species and testing their antiviral activity against group A rotaviruses.","limitations":"The study primarily focuses on specific strains and species, which may limit generalizability to all rotaviruses or other pathogens."},{"rthcId":"RPEP-06202","title":"Cost-effectiveness analysis of 4 GLP-1RAs in the treatment of obesity in a US setting.","authors":"Hu, Ying; Zheng, Shui-Lian; Ye, Xiao-Lan; Shi, Jia-Na; Zheng, Xiao-Wei; Pan, Han-Sheng; Zhang, Yi-Wen; Yang, Xiu-Li; Huang, Ping","year":2022,"journal":"Annals of translational medicine, 10(3), 152","doi":"10.21037/atm-22-200","pmid":"35284548","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06203","title":"Fish proteins as potential precursors of taste-active compounds: an in silico study.","authors":"Hu, Yun; Xiao, Naiyong; Ye, Yiting; Shi, Wenzheng","year":2022,"journal":"Journal of the science of food and agriculture, 102(14), 6404-6413","doi":"10.1002/jsfa.12006","pmid":"35562847","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Myosin and collagen proteins from fish contain significant amounts of taste-active peptides, with myosin rich in umami and collagen in sweet and bitter flavors.","whyItMatters":"Understanding how fish proteins contribute to flavor can enhance food ingredient development, leading to better taste experiences in products.","specificNumbers":"","methodology":"An in silico approach was used to analyze the protein sequences of six types of fish proteins and predict their taste-active compounds.","limitations":"The study is based on computational models, which may not fully capture real-world flavor interactions in food."},{"rthcId":"RPEP-06204","title":"Effect of Grass Carp Scale Collagen Peptide FTGML on cAMP-PI3K/Akt and MAPK Signaling Pathways in B16F10 Melanoma Cells and Correlation between Anti-Melanin and Antioxidant Properties.","authors":"Hu, Zizi; Sha, Xiaomei; Zhang, Lu; Huang, Sheng; Tu, Zongcai","year":2022,"journal":"Foods (Basel, Switzerland), 11(3)","doi":"10.3390/foods11030391","pmid":"35159541","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"FTGML significantly inhibited tyrosinase activity and melanin synthesis in B16F10 cells.","whyItMatters":"Understanding how FTGML affects melanin production could lead to new treatments for skin conditions related to pigmentation. It also highlights the potential of natural peptides in cancer research.","specificNumbers":"","methodology":"B16F10 melanoma cells were treated with FTGML to assess its effects on melanin production and signaling pathways.","limitations":"The study was conducted in vitro, and results may not fully translate to in vivo conditions in humans."},{"rthcId":"RPEP-06205","title":"Antimicrobial peptides/ciprofloxacin-loaded O-carboxymethyl chitosan/self-assembling peptides hydrogel dressing with sustained-release effect for enhanced anti-bacterial infection and wound healing.","authors":"Huan, Yuchen; Kong, Qing; Tang, Qingjuan; Wang, Yuming; Mou, Haijin; Ying, Rui; Li, Chunjun","year":2022,"journal":"Carbohydrate polymers, 280, 119033","doi":"10.1016/j.carbpol.2021.119033","pmid":"35027135","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Self-assembling peptides (SAPs) were grafted onto O-carboxymethyl chitosan (O-CMCS) to create a hydrogel with sustained-release properties for both mel-d1 (a modified melittin antimicrobial peptide with reduced cytotoxicity) and ciprofloxacin. The drug retention was enhanced by hydrophobic interactions and π-π stacking between the scaffold and the drugs. In vivo, the dual-loaded hydrogel accelerated wound closure and skin tissue regeneration in E. coli-infected mouse wounds. The SAP component itself contributed to tissue healing beyond its role as a drug carrier.","whyItMatters":"Wound infections — especially with antibiotic-resistant bacteria — are a growing healthcare crisis. Traditional wound dressings simply cover wounds; they don't actively fight infection or promote healing. This dual-drug hydrogel addresses both problems: the antimicrobial peptide and antibiotic kill bacteria through different mechanisms (reducing resistance risk), while the self-assembling peptide scaffold actively promotes tissue regeneration. The sustained-release design means fewer dressing changes and more consistent drug levels at the wound site.","specificNumbers":"","methodology":"Researchers synthesized O-CMCS/SAP hydrogels by grafting self-assembling peptides onto O-carboxymethyl chitosan. The hydrogel was loaded with mel-d1 (a melittin analog) and ciprofloxacin. Drug release kinetics were characterized, and the scaffold structure was analyzed. In vivo wound healing was tested in BALB/c mice with E. coli-induced skin infections, measuring wound closure and tissue regeneration.","limitations":"The study was performed only in mice, and wound healing in rodents differs significantly from humans (loose skin, different immune responses). Only E. coli infections were tested — efficacy against Gram-positive bacteria or mixed infections is unknown. The comparison to standard wound dressings or single-drug controls wasn't fully described in the abstract. The mel-d1 peptide was described as having 'the same antimicrobial activity but lower cytotoxicity' as melittin, but specific safety data weren't detailed."},{"rthcId":"RPEP-06206","title":"Pentadecapeptide BPC 157 efficiently reduces radiation-induced liver injury and lipid accumulation through Kruppel-like factor 4 upregulation both in vivo and in vitro.","authors":"Huang, Bing-Shen; Huang, Shih-Chiang; Chen, Fang-Hsin; Chang, Yu; Mei, Hsiu-Fu; Huang, Hsiu-Yun; Chen, Wan-Yu; Pang, Jong-Hwei Su","year":2022,"journal":"Life sciences, 310, 121072","doi":"10.1016/j.lfs.2022.121072","pmid":"36228773","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Oral BPC 157 reduced radiation-induced liver injury in mice irradiated with 12 Gy. Specifically, it lowered plasma AST and ALT levels (liver damage markers), inhibited hydropic degeneration of liver tissue, and significantly decreased radiation-induced cell death (apoptosis).\n\nBPC 157 increased PCNA expression (a marker of cell proliferation), promoted KLF4 expression, reduced hepatic lipid accumulation, and decreased HIF-2α expression in both mouse liver tissue and cultured rat liver cells. The critical finding: when KLF4 was knocked down using siRNA, BPC 157's protective effects on apoptosis and lipid accumulation were abolished — proving that KLF4 mediates BPC 157's liver-protective mechanism.","whyItMatters":"Radiation-induced liver disease (RILD) is a serious complication for cancer patients receiving abdominal radiation therapy, and there are no established pharmaceutical treatments for it. This study identifies a specific molecular mechanism (KLF4 upregulation) through which oral BPC 157 protects liver cells, moving beyond the typical 'BPC 157 helps everything' claims to pinpoint an actionable pathway. The oral route of administration is also significant, as most BPC 157 studies use injection.","specificNumbers":"12 Gy single radiation dose · Reduced AST and ALT · KLF4 knockdown abolished protection · Decreased HIF-2α expression · Oral administration","methodology":"Mice received a single 12 Gy radiation dose to induce acute liver injury, with or without oral BPC 157. Liver damage was assessed via plasma AST/ALT levels, tissue histology, TUNEL assay (apoptosis), lipid staining, and Western blotting for caspase-3, PCNA, KLF-4, and HIF-2α. Parallel in vitro experiments used rat liver clone 9 cells. The mechanism was confirmed by knocking down KLF4 with siRNA to show that BPC 157's protective effects depended on this specific transcription factor.","limitations":"This is a mouse/cell culture study — human liver responses to radiation and BPC 157 may differ. The radiation model used a single high dose (12 Gy) rather than the fractionated doses typically used in clinical radiation therapy. BPC 157 dosing details and pharmacokinetics after oral administration were not elaborated in the abstract. No long-term follow-up was reported."},{"rthcId":"RPEP-06207","title":"Removable Backbone Modification (RBM) Strategy for the Chemical Synthesis of Hydrophobic Peptides/Proteins.","authors":"Huang, Dong-Liang; Li, Ying; Zheng, Ji-Shen","year":2022,"journal":"Methods in molecular biology (Clifton, N.J.), 2530, 241-256","doi":"10.1007/978-1-0716-2489-0_16","pmid":"35761053","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The RBM strategy successfully enables the synthesis of hydrophobic peptides, demonstrated with a S-palmitoylated peptide.","whyItMatters":"This method could enhance the ability to create modified peptides that are otherwise difficult to produce, expanding research and therapeutic options. It bridges gaps in peptide synthesis technology.","specificNumbers":"","methodology":"The study outlines a three-step protocol involving solid-phase peptide synthesis, chemical ligation, and removal of modification tags.","limitations":"The study focuses on a specific example and may not address all types of hydrophobic peptides or proteins."},{"rthcId":"RPEP-06208","title":"Identification and functional analysis of three novel osteogenic peptides isolated from tilapia scale collagen hydrolysate.","authors":"Huang, Wen; Yu, Kenan; Kang, Meng; Wang, Qiaoe; Liao, Wanwen; Liang, Peng; Liu, Guo; Cao, Yong; Miao, Jianyin","year":2022,"journal":"Food research international (Ottawa, Ont.), 162(Pt A), 111993","doi":"10.1016/j.foodres.2022.111993","pmid":"36461299","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The peptides increased cell proliferation by 25%, 37%, and 56%, and mineralized calcium nodules by 166%, 161%, and 111%, respectively.","whyItMatters":"These findings could lead to new dietary strategies for osteoporosis prevention, benefiting public health. Understanding how these peptides work may also open new avenues in bone health research.","specificNumbers":"","methodology":"The study involved screening peptides for osteogenic properties through calcium-binding tests and molecular docking, followed by cell culture experiments to assess their effects on bone cells.","limitations":"The study was conducted in vitro, so results may not directly translate to human outcomes."},{"rthcId":"RPEP-06209","title":"Resistant starch wheat increases PYY and decreases GIP but has no effect on self-reported perceptions of satiety.","authors":"Hughes, Riley L; Horn, William F; Wen, Anita; Rust, Bret; Woodhouse, Leslie R; Newman, John W; Keim, Nancy L","year":2022,"journal":"Appetite, 168, 105802","doi":"10.1016/j.appet.2021.105802","pmid":"34774669","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"RS2-enriched wheat increased PYY3-36 levels and decreased GIP levels, but did not affect hunger perceptions.","whyItMatters":"Understanding how different types of dietary fiber affect hunger and gut hormones can help improve dietary recommendations for weight management. This study suggests that not all fibers impact satiety perceptions similarly.","specificNumbers":"","methodology":"A double-blind, randomized, placebo-controlled, crossover study with 30 healthy adults aged 40-65.","limitations":"The study's sample size was relatively small, and self-reported hunger measures may not fully capture satiety effects."},{"rthcId":"RPEP-06210","title":"Suvorexant ameliorated sleep disturbance, opioid withdrawal, and craving during a buprenorphine taper.","authors":"Huhn, Andrew S; Finan, Patrick H; Gamaldo, Charlene E; Hammond, Alexis S; Umbricht, Annie; Bergeria, Cecilia L; Strain, Eric C; Dunn, Kelly E","year":2022,"journal":"Science translational medicine, 14(650), eabn8238","doi":"10.1126/scitranslmed.abn8238","pmid":"35731889","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06211","title":"Basal ganglia neuropeptides show abnormal processing associated with L-DOPA-induced dyskinesia.","authors":"Hulme, Heather; Fridjonsdottir, Elva; Vallianatou, Theodosia; Shariatgorji, Reza; Nilsson, Anna; Li, Qin; Bezard, Erwan; Andrén, Per E","year":2022,"journal":"NPJ Parkinson's disease, 8(1), 41","doi":"10.1038/s41531-022-00299-7","pmid":"35418178","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Dyskinesia severity correlated with levels of abnormally processed peptides — des-tyrosine dynorphins, substance P (1-7), and substance P (1-9) — across multiple brain regions. Active neuropeptides (dynorphin B, dynorphin A (1-8), α-neoendorphin, substance P (1-11), neurokinin A) in the globus pallidus and substantia nigra correlated with putaminal L-DOPA concentrations. Truncated neuropeptides with reduced or altered receptor affinity correlated specifically with dyskinesia severity, particularly those in the direct pathway (dynorphins and tachykinins). The findings suggest increased neuropeptide tone in LID leads to abnormal processing as a compensatory mechanism.","whyItMatters":"Dyskinesia affects up to 80% of Parkinson's patients after 5-10 years of L-DOPA therapy and severely impacts quality of life. Current treatments are limited because the molecular mechanisms are poorly understood. This study reveals that the problem isn't simply too much or too little of certain neuropeptides — it's that they're being chopped into wrong-sized fragments with different biological activities. This shifts the therapeutic target from neuropeptide levels to neuropeptide processing enzymes.","specificNumbers":"","methodology":"Mass spectrometry imaging was used to visualize and quantify neuropeptides in brain tissue from MPTP-exposed parkinsonian Macaca mulatta (rhesus monkeys) with and without L-DOPA-induced dyskinesia. Regional mapping of both active neuropeptides and their truncated/abnormally processed forms was performed across basal ganglia structures. Correlations with dyskinesia severity and L-DOPA concentrations were calculated.","limitations":"Non-human primate model (macaque) — while the best animal model for Parkinson's dyskinesia, species differences exist. MPTP-induced parkinsonism differs from idiopathic human PD in progression pattern. The study is correlative — it cannot prove that abnormal neuropeptide processing causes dyskinesia rather than being a consequence. Sample sizes were not specified in the abstract. The mass spectrometry imaging approach, while powerful for spatial mapping, has detection limits that may miss some peptide species."},{"rthcId":"RPEP-06212","title":"Semaglutide reduces cardiovascular events regardless of metformin use: a post hoc subgroup analysis of SUSTAIN 6 and PIONEER 6.","authors":"Husain, Mansoor; Consoli, Agostino; De Remigis, Alessandra; Pettersson Meyer, Anna Sina; Rasmussen, Søren; Bain, Stephen","year":2022,"journal":"Cardiovascular diabetology, 21(1), 64","doi":"10.1186/s12933-022-01489-6","pmid":"35484580","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide reduced the risk of major adverse cardiovascular events (MACE) with hazard ratios of 0.70 for metformin users and 0.86 for non-users.","whyItMatters":"Understanding how semaglutide works for different patient groups can help tailor diabetes treatments and improve heart health outcomes. This could lead to better management strategies for patients at high cardiovascular risk.","specificNumbers":"","methodology":"The study involved a post hoc analysis of pooled data from the SUSTAIN 6 and PIONEER 6 trials, along with a meta-analysis of seven cardiovascular outcome trials.","limitations":"The analysis is based on post hoc data, which may limit the strength of the conclusions. Additionally, the study population may not represent all diabetes patients."},{"rthcId":"RPEP-06213","title":"Venom Peptide Toxins Targeting the Outer Pore Region of Transient Receptor Potential Vanilloid 1 in Pain: Implications for Analgesic Drug Development.","authors":"Hwang, Sung-Min; Jo, Youn-Yi; Cohen, Cinder Faith; Kim, Yong-Ho; Berta, Temugin; Park, Chul-Kyu","year":2022,"journal":"International journal of molecular sciences, 23(10)","doi":"10.3390/ijms23105772","pmid":"35628583","tags":["venom-peptides","pain","drug-development"],"studyType":"Review","evidenceStrength":"Review/Reference","keyFinding":"Various peptides isolated from venomous animals (spiders, scorpions, and others) can potently and selectively bind to the outer pore region of the TRPV1 ion channel — a key pain receptor. These venom peptides can either activate or inhibit TRPV1, and their specificity for this particular region of the receptor makes them valuable templates for designing new pain medications.\n\nTRPV1 is activated by multiple painful stimuli including heat, acid, and inflammatory chemicals, and contributes to both acute and chronic pain conditions. By targeting its outer pore rather than its ligand-binding site, venom peptides offer a mechanistically distinct approach to controlling pain signaling.","whyItMatters":"Chronic pain remains one of medicine's biggest challenges, and current treatments — particularly opioids — carry serious risks of addiction and overdose. TRPV1 has emerged as a promising non-opioid pain target, but early synthetic TRPV1 blockers caused dangerous side effects like loss of heat sensation. Venom-derived peptides that target a specific region of the receptor offer a potentially more selective approach, blocking pain without eliminating protective sensations. Nature's millions of years of venom evolution have produced highly precise molecular tools that drug developers are now learning to repurpose.","specificNumbers":"TRPV1 outer pore region · multiple venom species · polymodal receptor activation (heat, acid, inflammation)","methodology":"This is a narrative review examining published research on venom-derived peptide toxins that interact with the outer pore region of the TRPV1 ion channel. The authors analyzed the molecular mechanisms of peptide-receptor binding and discussed how these interactions could inform analgesic drug development.","limitations":"As a review, this does not present new experimental data. The venom peptide research discussed is largely preclinical — most peptides described have not been tested in human clinical trials for pain. The translation from venom peptide to viable drug faces significant challenges including stability, delivery, and potential toxicity."},{"rthcId":"RPEP-06214","title":"Semi-Biosynthetic Production of Surface-Binding Adhesive Antimicrobial Peptides Using Intein-Mediated Protein Ligation.","authors":"Hwang, Young Eun; Im, Seonghun; Cho, Ju Hyun; Lee, Wonsik; Cho, Byung-Kwan; Sung, Bong Hyun; Kim, Sun Chang","year":2022,"journal":"International journal of molecular sciences, 23(23)","doi":"10.3390/ijms232315202","pmid":"36499519","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The peptide His-NKC-Cys-DOPA5 was produced with a yield of 88.7% and showed effective antimicrobial properties.","whyItMatters":"This research addresses the need for effective antimicrobial coatings, which are crucial in preventing infections, especially in healthcare settings. The efficient production method could lead to widespread use in various applications.","specificNumbers":"","methodology":"The study utilized intein-mediated protein ligation to synthesize the antimicrobial peptide in E. coli, followed by purification and testing of its properties.","limitations":"The study primarily focuses on in vitro results, and further research is needed to confirm effectiveness in real-world applications."},{"rthcId":"RPEP-06215","title":"Effectiveness of anti-CGRP monoclonal antibodies on central symptoms of migraine.","authors":"Iannone, Luigi Francesco; De Cesaris, Francesco; Ferrari, Anita; Benemei, Silvia; Fattori, Davide; Chiarugi, Alberto","year":2022,"journal":"Cephalalgia : an international journal of headache, 42(13), 1323-1330","doi":"10.1177/03331024221111526","pmid":"35775208","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 80 chronic migraine patients who responded well to anti-CGRP antibodies (erenumab, fremanezumab, or galcanezumab), the drugs prevented not just the headache but also the anticipatory and accompanying symptoms of migraine. Most patients experienced complete prevention without evidence of an attack starting and being aborted. Only 10–12.5% reported residual prodromal symptoms without headache, and 1.3–8.8% had accompanying symptoms without headache. All patients with aura reported decreased aura incidence. Additional effects included sleep changes (51.2%), increased appetite (20%), weight gain (18.8%), reduced stress (45%), reduced anxiety (26.3%), and fewer panic attacks (15%).","whyItMatters":"Most migraine research focuses on headache frequency and severity, but migraine is far more than a headache — it includes prodromal symptoms, aura, nausea, light sensitivity, and cognitive changes. This study shows anti-CGRP antibodies don't just suppress pain; they appear to prevent the entire migraine cascade from initiating, which tells us something fundamental about how CGRP drives the disease.","specificNumbers":"","methodology":"This was an explorative, prospective, questionnaire-based study of 80 chronic migraine patients who had achieved a sustained response to anti-CGRP antibody treatment (≥50% reduction in Migraine Disability Assessment Score and ≥30% reduction in monthly migraine days at three months). Patients completed questionnaires about prodromal symptoms, accompanying symptoms, aura, and neurological/psychiatric changes during treatment with erenumab, fremanezumab, or galcanezumab.","limitations":"The study only included treatment responders (patients with ≥50% disability reduction), so results don't apply to non-responders. The sample size of 80 is modest. As a questionnaire-based study, it relies on patient recall. There was no placebo control group, so some improvements could reflect placebo effects or natural variation. The study did not distinguish effects between the three different antibodies."},{"rthcId":"RPEP-06216","title":"Long-Term Effectiveness of Three Anti-CGRP Monoclonal Antibodies in Resistant Chronic Migraine Patients Based on the MIDAS score.","authors":"Iannone, Luigi Francesco; Fattori, Davide; Benemei, Silvia; Chiarugi, Alberto; Geppetti, Pierangelo; De Cesaris, Francesco","year":2022,"journal":"CNS drugs, 36(2), 191-202","doi":"10.1007/s40263-021-00893-y","pmid":"35146696","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"All three anti-CGRP monoclonal antibodies showed similar effectiveness in this treatment-resistant population, with only 17.2% of patients dropping out over the study period.\n\nUsing the MIDAS disability score, 89.5–100% of patients achieved at least 50% reduction at various follow-up points, and 84.4–100% maintained this at 12 months. By comparison, the traditional ≥50% reduction in monthly migraine days was achieved by only 36.4–66.6% of patients — substantially lower.\n\nThis discrepancy suggests that MIDAS captures functional improvements (less disability per migraine day, better coping) that raw migraine day counts miss. Monthly analgesic use also decreased substantially, with 51.1–75.7% achieving ≥50% reduction.\n\n84.7% of enrolled patients also had medication overuse at baseline. No severe adverse events were recorded. Fewer baseline migraine days predicted better early response.","whyItMatters":"These patients represent the hardest-to-treat migraine population — chronic migraine with multiple prior treatment failures and medication overuse. Showing that anti-CGRP antibodies are effective and safe in this group for up to 12 months provides crucial real-world evidence. The finding that disability scores capture treatment benefits better than migraine day counts has important implications for how treatment success is measured and how insurance reimbursement criteria are set.","specificNumbers":"","methodology":"This was a single-center prospective cohort study at an Italian Headache Center enrolling 203 consecutive chronic migraine patients resistant to ≥3 previous preventive treatments. Patients received erenumab (47.2%), galcanezumab (36.5%), or fremanezumab (16.3%) for up to 12 months. Outcomes included monthly migraine days (MMDs), analgesic use, MIDAS score, HIT-6 score, and Patient Global Impression of Change. Responder rates (≥50%, ≥75%, 100% MMD reduction) were calculated at multiple follow-up points. Predictors of response were also assessed.","limitations":"This was a single-center study in Italy, which may limit generalizability to other populations and healthcare systems. There was no placebo control group. The three antibodies were not randomized but prescribed based on clinical judgment, making direct comparisons between them less reliable. The 12-month follow-up, while substantial, may not capture longer-term outcomes or late adverse effects."},{"rthcId":"RPEP-06217","title":"Down regulation of defensin genes during SARS-CoV-2 infection.","authors":"Idris, Mohammed M; Banu, Sarena; Siva, Archana B; Nagaraj, Ramakrishnan","year":2022,"journal":"Acta virologica, 66(3), 249-253","doi":"10.4149/av_2022_306","pmid":"36029089","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Of the defensin genes expressed in the nasopharyngeal/oropharyngeal cavity, nine were detected by qRT-PCR analysis. Four defensin genes were significantly downregulated in SARS-CoV-2-infected patients compared to controls: defensin beta 4A/B (encoding human beta-defensin 2), 106B (beta-defensin 6), 107B (beta-defensin 7), and 103A (beta-defensin 3).\n\nThese beta-defensins are known to have antiviral properties, and their suppression during infection suggests that SARS-CoV-2 may compromise the innate immune peptide defense system. The authors propose that defensin peptide-based therapy could be explored as a treatment approach to correct this immune suppression.","whyItMatters":"Defensins are among the body's most ancient and important immune defense peptides. Understanding that COVID-19 suppresses these natural antimicrobial peptides provides insight into why the virus can overcome initial immune defenses. More broadly, this suggests that boosting defensin levels — either through peptide-based therapies or immune modulators — could be a strategy for treating viral infections where innate peptide immunity is compromised.","specificNumbers":"","methodology":"Researchers collected nasopharyngeal/oropharyngeal swab samples originally taken for SARS-CoV-2 screening in early 2020 in Hyderabad, India. They selected 40 SARS-CoV-2-positive and 40 negative samples and analyzed defensin gene expression using quantitative real-time reverse transcription PCR (qRT-PCR) with gene-specific primers. Differential expression analysis was performed to identify significantly downregulated defensin genes.","limitations":"Relatively small sample size (40 per group) from a single location in India limits generalizability. Samples were from early 2020, before variants emerged, so results may not apply to later SARS-CoV-2 strains. Only gene expression was measured — actual defensin protein levels in the mucosa were not assessed. The study is observational and cannot determine whether defensin downregulation is a cause or consequence of disease progression. Clinical severity of the COVID-19 cases was not detailed."},{"rthcId":"RPEP-06218","title":"Free Radical Scavenging, Redox Balance and Wound Healing Activity of Bioactive Peptides Derived from Proteinase K-Assisted Hydrolysis of Hypophthalmichthys molitrix Skin Collagen.","authors":"Ilie, Daniela; Iosageanu, Andreea; Craciunescu, Oana; Seciu-Grama, Ana-Maria; Sanda, Catalina; Oancea, Florin","year":2022,"journal":"Food technology and biotechnology, 60(3), 281-292","doi":"10.17113/ftb.60.03.22.7107","pmid":"36320350","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Bioactive peptides from carp skin showed significantly higher antioxidant activity and improved fibroblast migration.","whyItMatters":"These findings highlight the potential of fish skin peptides in developing new treatments for skin aging and wound healing, which could benefit both medical and cosmetic industries.","specificNumbers":"","methodology":"The study involved two-step enzymatic hydrolysis of fish skin collagen using proteinase K, followed by in vitro testing of the peptides' biological activities.","limitations":"The study was conducted in vitro, so results may not directly translate to in vivo applications in humans."},{"rthcId":"RPEP-06219","title":"Innate immune response of human periodontal ligament fibroblasts via the Dectin-1/Syk pathway.","authors":"Inomata, Megumi; Amano, Shigeru; Abe, Masayo; Hayashi, Toru; Sakagami, Hiroshi","year":2022,"journal":"Journal of medical microbiology, 71(12)","doi":"10.1099/jmm.0.001627","pmid":"36748551","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Human periodontal ligament fibroblasts (PDLFs) constitutively express the fungal pattern recognition receptor Dectin-1. Stimulation with zymosan (β-glucan-rich fungal component) induced expression of cytokines IL-6, IL-1β, and IL-17A, chemokine IL-8, and the antimicrobial peptide β-defensin-1 (DEFB1), along with phosphorylation of Syk and NF-κB.\n\nHeat-killed Candida albicans similarly induced IL-6, IL-17A, IL-8, and DEFB1 expression in PDLFs, and this response was suppressed by the Syk inhibitor R406 — confirming the Dectin-1/Syk pathway as the specific mechanism. This demonstrates that gum tissue fibroblasts are active participants in antifungal innate immunity, not just structural support cells.","whyItMatters":"Periodontal disease affects nearly half of adults and can be worsened by fungal infections, especially in immunocompromised patients. Discovering that gum tissue cells have their own antifungal defense system — including antimicrobial peptide production — opens new possibilities for understanding and treating oral infections, particularly in patients prone to candidiasis.","specificNumbers":"","methodology":"Dectin-1 expression in PDLFs was confirmed by flow cytometry, Western blotting, and confocal microscopy. Immune responses to β-glucan-rich zymosan and heat-killed C. albicans were measured by real-time PCR and Western blotting for cytokines, chemokines, antimicrobial peptides, and signaling molecules. The Syk inhibitor R406 was used to confirm pathway specificity.","limitations":"This was an in vitro study using isolated fibroblasts, which does not capture the complex interactions between multiple cell types, saliva, and the full oral microbiome present in vivo. Only heat-killed C. albicans was used, not live fungi. The study did not assess whether β-defensin-1 protein was secreted at functional antimicrobial concentrations."},{"rthcId":"RPEP-06220","title":"In Vitro Antimycobacterial Activity of Human Lactoferrin-Derived Peptide, D-hLF 1-11, against Susceptible and Drug-Resistant Mycobacterium tuberculosis and Its Synergistic Effect with Rifampicin.","authors":"Intorasoot, Sorasak; Intorasoot, Amornrat; Tawteamwong, Arocha; Butr-Indr, Bordin; Phunpae, Ponrut; Tharinjaroen, Chayada Sitthidet; Wattananandkul, Usanee; Sangboonruang, Sirikwan; Khantipongse, Jiaranai","year":2022,"journal":"Antibiotics (Basel, Switzerland), 11(12)","doi":"10.3390/antibiotics11121785","pmid":"36551443","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"D-hLF 1-11 inhibited M. tuberculosis growth with a minimum inhibitory concentration of 100-200 µg/mL.","whyItMatters":"With rising drug-resistant tuberculosis cases, finding new treatment options is critical. D-hLF 1-11 could be a valuable addition to current therapies.","specificNumbers":"","methodology":"The study used colorimetric assays, microplate assays, and microscopic observations to evaluate the peptide's antimycobacterial activity.","limitations":"The study was conducted in vitro, so results may not directly translate to human treatments."},{"rthcId":"RPEP-06221","title":"Vitamin D, infections and immunity.","authors":"Ismailova, Aiten; White, John H","year":2022,"journal":"Reviews in endocrine & metabolic disorders, 23(2), 265-277","doi":"10.1007/s11154-021-09679-5","pmid":"34322844","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Vitamin D deficiency is linked to higher rates of infections and poor immune responses.","whyItMatters":"Understanding vitamin D's role in immune function can help develop strategies to improve health outcomes during infectious diseases. This is especially relevant in the context of ongoing health crises like COVID-19.","specificNumbers":"","methodology":"The study is a review that synthesizes existing laboratory and epidemiological evidence on vitamin D's role in immunity.","limitations":"The review is based on existing literature and may not include all recent studies or clinical trials."},{"rthcId":"RPEP-06222","title":"Signature Effects of Vector-Guided Systemic Nano Bioconjugate Delivery Across Blood-Brain Barrier of Normal, Alzheimer's, and Tumor Mouse Models.","authors":"Israel, Liron L; Galstyan, Anna; Cox, Alysia; Shatalova, Ekaterina S; Sun, Tao; Rashid, Mohammad-Harun; Grodzinski, Zachary; Chiechi, Antonella; Fuchs, Dieu-Trang; Patil, Rameshwar; Koronyo-Hamaoui, Maya; Black, Keith L; Ljubimova, Julia Y; Holler, Eggehard","year":2022,"journal":"ACS nano, 16(8), 11815-11832","doi":"10.1021/acsnano.1c10034","pmid":"35961653","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The BBB permeation was most efficient in tumor models, followed by normal and Alzheimer's models.","whyItMatters":"Improving drug delivery to the brain is crucial for treating neurological diseases, including Alzheimer's and brain tumors. This research could lead to more effective therapies for these conditions.","specificNumbers":"","methodology":"The study involved creating peptide-polymer nanoconjugates and testing their ability to cross the BBB in different mouse models.","limitations":"The study was conducted in mouse models, which may not fully replicate human responses."},{"rthcId":"RPEP-06223","title":"Phage display-based discovery of cyclic peptides against the broad spectrum bacterial anti-virulence target CsrA.","authors":"Jakob, Valentin; Zoller, Ben G E; Rinkes, Julia; Wu, Yingwen; Kiefer, Alexander F; Hust, Michael; Polten, Saskia; White, Andrew M; Harvey, Peta J; Durek, Thomas; Craik, David J; Siebert, Andreas; Kazmaier, Uli; Empting, Martin","year":2022,"journal":"European journal of medicinal chemistry, 231, 114148","doi":"10.1016/j.ejmech.2022.114148","pmid":"35114538","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Key findings from this phage display-based peptide discovery:\n\n- A disulfide-bridged cyclic heptapeptide was identified that binds CsrA from Yersinia pseudotuberculosis and displaces bound RNA\n- IC50 in the low micromolar range\n- Cyclization was essential — linear versions lost activity\n- A redox-stable triazole analogue (replacing the disulfide bridge) showed activity in the double-digit micromolar range with improved metabolic stability\n- The triazole peptidomimetic was also active against:\n  - CsrA from Escherichia coli\n  - RsmA from Pseudomonas aeruginosa\n- This demonstrates broad-spectrum anti-virulence potential across multiple pathogenic species","whyItMatters":"Antibiotic resistance is a global crisis, and traditional antibiotics that kill bacteria create strong selection pressure for resistance. Anti-virulence drugs take a fundamentally different approach: they disarm bacteria without killing them, theoretically reducing resistance pressure. CsrA is an especially attractive target because it controls virulence in many dangerous bacterial species. A single drug that blocks CsrA across species could be a powerful tool against infections caused by E. coli, Pseudomonas, Yersinia, and other pathogens.","specificNumbers":"","methodology":"Phage display screening using a self-designed cyclic peptide library was used to identify peptides binding to CsrA from Yersinia pseudotuberculosis. Hit peptides were characterized for binding affinity, RNA displacement activity, and the importance of cyclization. To improve metabolic stability, the disulfide bridge was replaced with various stable mimetics, including a 1,4-disubstituted 1,2,3-triazole. Cross-species activity was tested against CsrA from E. coli and RsmA from P. aeruginosa.","limitations":"All data are from in vitro biochemical assays — no bacterial growth inhibition, biofilm disruption, or animal infection studies were conducted. The triazole analogue showed reduced potency (double-digit micromolar) compared to the original disulfide peptide (low micromolar). Metabolic stability, cell permeability, and pharmacokinetics in animals are unknown. Whether blocking CsrA alone is sufficient to attenuate virulence in vivo has not been demonstrated. The peptide library was custom-designed and may not represent all possible binding solutions."},{"rthcId":"RPEP-06224","title":"Tirzepatide Once Weekly for the Treatment of Obesity.","authors":"Jastreboff, Ania M; Aronne, Louis J; Ahmad, Nadia N; Wharton, Sean; Connery, Lisa; Alves, Breno; Kiyosue, Arihiro; Zhang, Shuyu; Liu, Bing; Bunck, Mathijs C; Stefanski, Adam","year":2022,"journal":"The New England journal of medicine, 387(3), 205-216","doi":"10.1056/NEJMoa2206038","pmid":"35658024","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tirzepatide, a dual GIP/GLP-1 receptor agonist, produced dose-dependent weight loss that far exceeded placebo in adults with obesity but without diabetes. At week 72, mean weight loss was 15.0% with 5 mg, 19.5% with 10 mg, and 20.9% with 15 mg, compared to just 3.1% with placebo (P<0.001 for all comparisons).\n\nAt the highest dose, 91% of participants lost at least 5% of their body weight and 57% lost at least 20% — a threshold previously achievable mainly through bariatric surgery. Improvements were observed across all prespecified cardiometabolic measures. Gastrointestinal side effects were the most common but were predominantly mild to moderate and occurred primarily during the 20-week dose-escalation period.","whyItMatters":"This trial established tirzepatide as one of the most effective anti-obesity medications ever tested, producing weight loss approaching what was previously only seen with surgery. As the pivotal trial supporting Zepbound's FDA approval for obesity, SURMOUNT-1 reshaped expectations for what pharmacotherapy can achieve in weight management and opened the door for a new class of dual-agonist peptide drugs.","specificNumbers":"","methodology":"This was the SURMOUNT-1 trial — a phase 3, double-blind, randomized, placebo-controlled study. A total of 2,539 adults with a BMI of 30 or higher (or 27+ with at least one weight-related complication), excluding those with diabetes, were randomly assigned 1:1:1:1 to receive subcutaneous tirzepatide at 5 mg, 10 mg, or 15 mg, or placebo, once weekly for 72 weeks. Doses were gradually escalated over the first 20 weeks. The two primary endpoints were percentage change in body weight and the proportion achieving at least 5% weight loss.","limitations":"The trial excluded people with diabetes, so results may not directly apply to that population (separate trials addressed this). The 72-week duration, while substantial, does not answer questions about weight maintenance after stopping the drug. The study population was predominantly female and had a mean BMI of 38, so results may vary in other demographics. Gastrointestinal side effects led to discontinuation in up to 7.1% of participants at the 10 mg dose."},{"rthcId":"RPEP-06225","title":"Liposomes encapsulating novel antimicrobial peptide Omiganan: Characterization and its pharmacodynamic evaluation in atopic dermatitis and psoriasis mice model.","authors":"Javia, Ankit; Misra, Ambikanandan; Thakkar, Hetal","year":2022,"journal":"International journal of pharmaceutics, 624, 122045","doi":"10.1016/j.ijpharm.2022.122045","pmid":"35878872","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Omiganan liposomal gel reduced pro-inflammatory cytokines and improved skin lesions significantly compared to conventional formulations.","whyItMatters":"This research highlights a potential new treatment for chronic skin conditions, which can significantly impact patients' quality of life. The findings could lead to better therapeutic options in dermatology.","specificNumbers":"","methodology":"The study involved creating liposomes encapsulating Omiganan and evaluating their efficacy in mice models of atopic dermatitis and psoriasis.","limitations":"The study was conducted in mice, and results may not directly translate to humans. Further clinical trials are needed."},{"rthcId":"RPEP-06226","title":"Changing Patterns of Antihyperglycaemic Treatment among Patients with Type 2 Diabetes in Hungary between 2015 and 2020-Nationwide Data from a Register-Based Analysis.","authors":"Jermendy, György; Kiss, Zoltán; Rokszin, György; Abonyi-Tóth, Zsolt; Lengyel, Csaba; Kempler, Péter; Wittmann, István","year":2022,"journal":"Medicina (Kaunas, Lithuania), 58(10)","doi":"10.3390/medicina58101382","pmid":"36295543","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Metformin monotherapy was the most common treatment in 2020, used by 31% of patients.","whyItMatters":"Understanding treatment patterns helps identify gaps in diabetes care and the need for timely adoption of new therapies. This can improve patient outcomes and align treatments with current scientific recommendations.","specificNumbers":"","methodology":"The study used a retrospective analysis of data from the National Health Insurance Fund in Hungary.","limitations":"The study is retrospective and may not capture all treatment changes or patient outcomes."},{"rthcId":"RPEP-06227","title":"Pepaxto: A New Peptide-Drug Conjugate for Heavily Pretreated Relapsed and Refractory Multiple Myeloma.","authors":"Jessee, Jeremiah K","year":2022,"journal":"The Annals of pharmacotherapy, 56(8), 951-957","doi":"10.1177/10600280211058388","pmid":"34963319","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06228","title":"Safety and efficacy of a GLP-1 and glucagon receptor dual agonist mazdutide (IBI362) 9 mg and 10 mg in Chinese adults with overweight or obesity: A randomised, placebo-controlled, multiple-ascending-dose phase 1b trial.","authors":"Ji, Linong; Gao, Leili; Jiang, Hongwei; Yang, Jing; Yu, Lei; Wen, Jie; Cai, Chenghang; Deng, Huan; Feng, Liqi; Song, Baili; Ma, Qingyang; Qian, Lei","year":2022,"journal":"EClinicalMedicine, 54, 101691","doi":"10.1016/j.eclinm.2022.101691","pmid":"36247927","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Participants taking 9 mg of mazdutide lost an average of 11.7% of their body weight, compared to 1.8% in the placebo group.","whyItMatters":"The results indicate that mazdutide could be an effective treatment for obesity, addressing a significant health issue. Its favorable safety profile is also encouraging for future use.","specificNumbers":"","methodology":"The study was a randomized, placebo-controlled trial involving multiple ascending doses of mazdutide over 12 to 16 weeks.","limitations":"The small sample size and short duration limit the generalizability of the findings."},{"rthcId":"RPEP-06229","title":"A Substance P (SP)/Neurokinin-1 Receptor Axis Promotes Perineural Invasion of Pancreatic Cancer and Is Affected by lncRNA LOC389641.","authors":"Ji, Tengfei; Ma, Keqiang; Wu, Hongsheng; Cao, Tiansheng","year":2022,"journal":"Journal of immunology research, 2022, 5582811","doi":"10.1155/2022/5582811","pmid":"35600049","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"SP significantly enhanced cancer cell proliferation, migration, and perineural invasion.","whyItMatters":"Understanding the mechanisms behind nerve invasion in pancreatic cancer could lead to new therapeutic strategies. Targeting the SP/NK-1R axis may improve patient outcomes.","specificNumbers":"","methodology":"The study involved coculturing pancreatic cancer cell lines with nerve cells and assessing various cellular behaviors after SP treatment.","limitations":"The study is limited to in vitro experiments, which may not fully represent in vivo conditions. Further research is needed to confirm these findings in animal models or clinical settings."},{"rthcId":"RPEP-06230","title":"Substance P and Glucagon-like Peptide-17-36 Amide Mediate Anorexic Responses to Trichothecene Deoxynivalenol and Its Congeners.","authors":"Jia, Hui; Qin, Zihui; Wei, Ben; Guo, Xinyi; Xiao, Huiping; Zhang, Huayue; Li, Zelin; Wu, Qinghua; Zheng, Ruibo; Wu, Wenda","year":2022,"journal":"Toxins, 14(12)","doi":"10.3390/toxins14120885","pmid":"36548782","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Substance P and GLP-1 levels increased significantly after exposure to trichothecenes, with effects lasting over 6 hours.","whyItMatters":"Understanding how these toxins affect appetite can help in developing strategies to mitigate their health impacts. This research sheds light on the biological mechanisms behind toxin-induced anorexia.","specificNumbers":"","methodology":"The study involved administering type B trichothecenes both intraperitoneally and orally to assess the resulting changes in brain-gut peptide levels and appetite responses.","limitations":"The study primarily focuses on animal models, which may not fully translate to human responses."},{"rthcId":"RPEP-06231","title":"PDGF-BB-derived supramolecular hydrogel for promoting skin wound healing.","authors":"Jian, Ke; Yang, Chenghao; Li, Tingting; Wu, Xia; Shen, Jun; Wei, Jiaying; Yang, Zhimou; Yuan, Dan; Zhao, Mingyi; Shi, Junfeng","year":2022,"journal":"Journal of nanobiotechnology, 20(1), 201","doi":"10.1186/s12951-022-01390-0","pmid":"35473604","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The hydrogel increased neovascularization density marked by CD31 on Day 3 and enhanced collagen deposition by Day 12.","whyItMatters":"Chronic wounds are a significant healthcare issue, and this hydrogel could offer a more effective treatment option. It may reduce costs and improve patient outcomes in wound care.","specificNumbers":"","methodology":"The study involved creating a PDGF-mimicking peptide that self-assembles into a hydrogel, followed by testing its effects on full-thickness skin wounds in healthy mice.","limitations":"The study was conducted in healthy mice, so results may not directly translate to humans or those with chronic wounds."},{"rthcId":"RPEP-06232","title":"Advance and Designing Strategies in Polymeric Antifungal Agents Inspired by Membrane-Active Peptides.","authors":"Jiang, Weinan; Wu, Yueming; Zhou, Min; Song, Gonghua; Liu, Runhui","year":2022,"journal":"Chemistry (Weinheim an der Bergstrasse, Germany), 28(65), e202202226","doi":"10.1002/chem.202202226","pmid":"35996361","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The study emphasizes the effectiveness of peptide-inspired synthetic antifungal agents.","whyItMatters":"Invasive fungal infections pose a significant risk to immunocompromised patients, and new antifungal strategies are urgently needed. This research could lead to the development of more effective treatments.","specificNumbers":"","methodology":"This is a concept article discussing the design and potential of synthetic antifungal polymers.","limitations":"As a concept article, it does not present experimental data or clinical trials to support the proposed strategies."},{"rthcId":"RPEP-06233","title":"Safety and efficacy of peptide receptor radionuclide therapy with 177Lu-DOTA-EB-TATE in patients with metastatic neuroendocrine tumors.","authors":"Jiang, Yuanyuan; Liu, Qingxing; Wang, Guochang; Sui, Huimin; Wang, Rongxi; Wang, Jiarou; Zhang, Jingjing; Zhu, Zhaohui; Chen, Xiaoyuan","year":2022,"journal":"Theranostics, 12(15), 6437-6445","doi":"10.7150/thno.77219","pmid":"36185603","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The treatment resulted in a 33.3% response rate and an 85.2% disease control rate.","whyItMatters":"This therapy could provide a new effective option for patients with metastatic NETs, which currently have limited treatment choices. Its favorable safety profile is also significant for patient quality of life.","specificNumbers":"","methodology":"Thirty patients with metastatic NETs were treated with 177Lu-DOTA-EB-TATE in three cycles, and outcomes were assessed using established criteria.","limitations":"The study had a small sample size and lacked a control group, which may limit the generalizability of the findings."},{"rthcId":"RPEP-06234","title":"A Pt(IV)-conjugated brain penetrant macrocyclic peptide shows pre-clinical efficacy in glioblastoma.","authors":"Jimenez-Macias, J L; Lee, Y-C; Miller, E; Finkelberg, T; Zdioruk, M; Berger, G; Farquhar, C E; Nowicki, M O; Cho, C-F; Fedeles, B I; Loas, A; Pentelute, B L; Lawler, S E","year":2022,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 352, 623-636","doi":"10.1016/j.jconrel.2022.10.051","pmid":"36349615","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Median survival for mice treated with Pt(IV)-M13 was 33 days compared to 24 days for the Pt(IV) prodrug and 22.5 days for cisplatin.","whyItMatters":"This research addresses a significant challenge in treating glioblastoma by improving drug delivery to the brain. It opens new avenues for developing effective therapies for this aggressive cancer.","specificNumbers":"","methodology":"The study involved synthesizing a peptide-drug conjugate and testing its effects in vitro and in mouse models of glioblastoma.","limitations":"The study was conducted in mouse models, which may not fully replicate human responses. Further research is needed to evaluate safety and efficacy in humans."},{"rthcId":"RPEP-06235","title":"Codon optimization of chicken β Gallinacin-3 gene results in constitutive expression and enhanced antimicrobial activity in transgenic Medicago sativa L.","authors":"Jin, Libo; Wang, Yunpeng; Liu, Xiuming; Peng, Renyi; Lin, Sue; Sun, Da; Ji, Hao; Wang, Lei; Zhang, Yuting; Ahmad, Naveed","year":2022,"journal":"Gene, 835, 146656","doi":"10.1016/j.gene.2022.146656","pmid":"35680025","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The Minimum Inhibitory Concentration (MIC) for E. coli, S. aureus, and S. typhi were 32, 16, and 128 μg/mL, respectively.","whyItMatters":"This research provides a new method for producing antimicrobial proteins in plants, which could enhance food safety and plant health. It also opens avenues for developing crops resistant to pathogens.","specificNumbers":"","methodology":"The study involved codon optimization of the Gal-3 gene, construction of an expression vector, and creation of transgenic Medicago sativa plants, followed by antimicrobial activity testing.","limitations":"The study primarily focuses on plant expression and in vitro antimicrobial activity, with limited insights into long-term effects on animal health."},{"rthcId":"RPEP-06236","title":"A Potent Micron Neoantigen Tumor Vaccine GP-Neoantigen Induces Robust Antitumor Activity in Multiple Tumor Models.","authors":"Jing, Zhe; Wang, Shuqing; Xu, Keyuan; Tang, Qian; Li, Wenjing; Zheng, Wei; Shi, Haobo; Su, Kailing; Liu, Yanting; Hong, Zhangyong","year":2022,"journal":"Advanced science (Weinheim, Baden-Wurttemberg, Germany), 9(24), e2201496","doi":"10.1002/advs.202201496","pmid":"35712770","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The vaccine induced robust CD8+ T cell responses and achieved complete tumor clearance in multiple models.","whyItMatters":"This research is significant as it addresses challenges in cancer immunotherapy by enhancing immune responses against tumors. The findings could lead to more effective personalized cancer vaccines.","specificNumbers":"","methodology":"The study involved creating a neoantigen vaccine using β-1,3-glucan particles and testing its effects on various cancer models in mice.","limitations":"The study was conducted in mice, and results may not directly translate to humans. Further clinical trials are needed."},{"rthcId":"RPEP-06237","title":"Antimicrobial peptides: Defending the mucosal epithelial barrier.","authors":"Johnstone, Karen F; Herzberg, Mark C","year":2022,"journal":"Frontiers in oral health, 3, 958480","doi":"10.3389/froh.2022.958480","pmid":"35979535","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Calprotectin and defensins work together to fortify the epithelial barrier against infections, with calprotectin protecting against neonatal sepsis.","whyItMatters":"Understanding how AMPs function can lead to new strategies for preventing infections, especially in vulnerable populations. This knowledge is crucial for developing therapies that enhance innate immunity.","specificNumbers":"","methodology":"This review synthesizes existing research on the roles of antimicrobial peptides in mucosal immunity, particularly focusing on defensins and calprotectin.","limitations":"The study primarily reviews existing literature and does not present new experimental data."},{"rthcId":"RPEP-06238","title":"The therapeutic potential of GLP-1 receptor biased agonism.","authors":"Jones, Ben","year":2022,"journal":"British journal of pharmacology, 179(4), 492-510","doi":"10.1111/bph.15497","pmid":"33880754","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06239","title":"Melittin-derived peptides exhibit variations in cytotoxicity and antioxidant, anti-inflammatory and allergenic activities.","authors":"Jung, Haesoo; Kim, Yong Soo; Jung, Da-Min; Lee, Kyeong-Seob; Lee, Jung-Min; Kim, Kee K","year":2022,"journal":"Animal cells and systems, 26(4), 158-165","doi":"10.1080/19768354.2022.2099971","pmid":"36046032","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The melittin-derived peptide P1 (sequence TTGLPALISWIKRKRQQ) maintained anti-inflammatory effects comparable to melittin, including inhibition of inflammatory cytokine mRNA expression and IκBα phosphorylation in RAW 264.7 macrophage cells. P1 also showed antioxidant activity comparable to full-length melittin in ABTS radical scavenging assays.\n\nCritically, P1 showed negligible cytotoxicity in MTS assays (unlike melittin's high toxicity) and remarkably reduced allergenicity compared to melittin, as measured by β-hexosaminidase release from RBL-2H3 mast cells. This separation of therapeutic activity from toxic side effects represents a significant advance in bee venom peptide engineering.","whyItMatters":"Bee venom therapy has been used for centuries for inflammatory conditions, but melittin's toxicity and allergenicity have prevented it from becoming a mainstream medicine. By identifying a fragment that preserves the anti-inflammatory mechanism while eliminating the dangerous side effects, this study opens a practical path toward developing safe, standardized peptide drugs from bee venom — replacing an unpredictable traditional remedy with a precisely engineered therapeutic.","specificNumbers":"","methodology":"Researchers generated hydrolyzed melittin-derived peptides and evaluated them using multiple in vitro assays: ABTS radical scavenging for antioxidant activity, MTS assay for cytotoxicity in cell cultures, qPCR and Western blot for inflammatory marker expression in RAW 264.7 macrophages, and β-hexosaminidase release assay in RBL-2H3 mast cells for allergenic activity.","limitations":"All experiments were conducted in vitro using cell lines, not in animal models or humans. The P1 peptide's stability, pharmacokinetics, and in vivo efficacy are unknown. Only one cell type was used for each assay, so the findings may not reflect responses across different tissues. The mechanism of P1's reduced toxicity was not fully elucidated."},{"rthcId":"RPEP-06240","title":"The anti-nociceptive effect of BPC-157 on the incisional pain model in rats.","authors":"Jung, Young-Hoon; Kim, Haekyu; Kim, Hyaejin; Kim, Eunsoo; Baik, Jiseok; Kang, Hyunjong","year":2022,"journal":"Journal of dental anesthesia and pain medicine, 22(2), 97-105","doi":"10.17245/jdapm.2022.22.2.97","pmid":"35449779","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BPC-157 significantly increased pain thresholds at 2 hours and 4 days post-incision compared to control.","whyItMatters":"Understanding how BPC-157 affects pain can help in developing better pain management strategies after surgeries. Its potential short-term effectiveness could be useful in clinical settings.","specificNumbers":"","methodology":"Sprague-Dawley rats were divided into groups receiving different doses of BPC-157 or morphine, and pain responses were measured after surgical incisions.","limitations":"The study was conducted on rats, so results may not directly apply to humans. The effects were also short-lived."},{"rthcId":"RPEP-06241","title":"An insight into gastrointestinal macromolecule delivery using physical oral devices.","authors":"Kaffash, Ehsan; Shahbazi, Mohammad-Ali; Hatami, Hooman; Nokhodchi, Ali","year":2022,"journal":"Drug discovery today, 27(8), 2309-2321","doi":"10.1016/j.drudis.2022.04.014","pmid":"35460891","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Recent physical methods show promise in improving oral bioavailability of macromolecules.","whyItMatters":"Improving oral delivery methods for macromolecules could lead to more effective treatments. This could enhance patient compliance and expand the therapeutic use of peptides.","specificNumbers":"","methodology":"This is a review study analyzing various physical methods for enhancing oral delivery of macromolecules.","limitations":"As a review, it does not provide original experimental data and may not cover all emerging technologies."},{"rthcId":"RPEP-06242","title":"Methodological advances in the design of peptide-based vaccines.","authors":"Kalita, Parismita; Tripathi, Timir","year":2022,"journal":"Drug discovery today, 27(5), 1367-1380","doi":"10.1016/j.drudis.2022.03.004","pmid":"35278703","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06243","title":"The Activity of Antimicrobial Peptides in Pediatric Celiac Disease.","authors":"Kamilova, Altinoy T; Azizova, Gulnoza K; Umarnazarova, Zulkhumar E; Abdullaeva, Dilrabo A; Geller, Svetlana I","year":2022,"journal":"Frontiers in pediatrics, 10, 873793","doi":"10.3389/fped.2022.873793","pmid":"35733815","tags":["antimicrobial-peptides","defensins"],"studyType":"case-control","evidenceStrength":"moderate","keyFinding":"Children with active celiac disease had significantly elevated fecal β-defensin-2 levels (99.6 vs 64.0 ng/mL, p<0.001) and higher anti-BPI antibodies compared to healthy controls. Fecal calprotectin and β-defensin-2 were moderately correlated (r=0.69), and β-defensin-2 weakly correlated with anti-BPI antibodies (r=0.35). These findings suggest that antimicrobial peptides are part of the gut's innate immune response in celiac disease.","whyItMatters":"Celiac disease diagnosis and monitoring still rely heavily on invasive biopsies and antibody tests. Fecal biomarkers like β-defensin-2 could offer a non-invasive way to assess intestinal inflammation and immune activation in children with celiac disease, potentially helping track disease activity without repeated endoscopies.","specificNumbers":"n=108 (76 CD, 32 controls) · β-defensin-2: 99.6 vs 64.0 ng/mL (p<0.001) · Calprotectin-defensin correlation r=0.69 · Defensin-anti-BPI correlation r=0.35","methodology":"Case-control study of 76 children (ages 2-10) with recently diagnosed celiac disease and 32 age-matched healthy controls. Measured fecal β-defensin-2 and calprotectin levels in stool samples and anti-BPI antibodies in blood serum. Correlations between markers assessed using Pearson coefficient.","limitations":"Relatively small sample size, especially the control group (32 children). Cross-sectional design cannot determine whether elevated AMPs are a cause or consequence of celiac inflammation. Did not follow patients after starting a gluten-free diet to see if biomarkers normalized. Age range limited to 2-10 years."},{"rthcId":"RPEP-06244","title":"In Vitro and In Vivo Evaluation of Lacticaseibacillus rhamnosus GG and Bifidobacterium lactis Bb12 Against Avian Pathogenic Escherichia coli and Identification of Novel Probiotic-Derived Bioactive Peptides.","authors":"Kathayat, Dipak; Closs, Gary; Helmy, Yosra A; Deblais, Loic; Srivastava, Vishal; Rajashekara, Gireesh","year":2022,"journal":"Probiotics and antimicrobial proteins, 14(6), 1012-1028","doi":"10.1007/s12602-021-09840-1","pmid":"34458959","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"L. rhamnosus GG reduced APEC colonization in chickens by approximately 1.6 logs.","whyItMatters":"With rising antibiotic resistance, finding effective alternatives like probiotics is crucial for poultry health and food safety. This research supports the potential for probiotics to reduce reliance on antibiotics in animal farming.","specificNumbers":"","methodology":"The study employed agar-well diffusion assays and co-culture assays to evaluate the probiotics' anti-APEC activity, followed by in vivo testing in chickens.","limitations":"The study primarily focused on in vitro and initial in vivo testing, and further research is needed to optimize probiotic delivery methods for practical use."},{"rthcId":"RPEP-06245","title":"Neurobiology of the Orexin System and Its Potential Role in the Regulation of Hedonic Tone.","authors":"Katzman, Martin A; Katzman, Matthew P","year":2022,"journal":"Brain sciences, 12(2)","doi":"10.3390/brainsci12020150","pmid":"35203914","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06246","title":"Isolation of bioactive peptides and multiple nutraceuticals of antidiabetic and antioxidant functionalities through sprouting: Recent advances.","authors":"Kehinde, Bababode Adesegun; Majid, Ishrat; Hussain, Shafat","year":2022,"journal":"Journal of food biochemistry, 46(10), e14317","doi":"10.1111/jfbc.14317","pmid":"35867040","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Sprouting enhances the release of bioactive peptides and increases total phenolic content.","whyItMatters":"Understanding how sprouting improves vegetable nutrition can lead to better dietary choices and health outcomes, particularly for managing conditions like diabetes.","specificNumbers":"","methodology":"The study reviews recent advances in the use of sprouting to enhance the nutritional profile of vegetables and the mechanisms involved.","limitations":"The study primarily reviews existing literature and may not include new experimental data."},{"rthcId":"RPEP-06247","title":"Senescence-Associated Secretory Phenotype of Cardiovascular System Cells and Inflammaging: Perspectives of Peptide Regulation.","authors":"Khavinson, Vladimir; Linkova, Natalia; Dyatlova, Anastasiia; Kantemirova, Raisa; Kozlov, Kirill","year":2022,"journal":"Cells, 12(1)","doi":"10.3390/cells12010106","pmid":"36611900","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06248","title":"Opposing Roles of Antimicrobial Peptides in Skin Cancers.","authors":"Kiatsurayanon, Chanisa; Peng, Ge; Niyonsaba, François","year":2022,"journal":"Current pharmaceutical design, 28(3), 248-258","doi":"10.2174/1381612827666211021163318","pmid":"34674617","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"AMPs have both pro-tumor and anti-cancer properties, with specific AMPs linked to skin cancer.","whyItMatters":"Understanding the dual roles of AMPs could lead to new strategies for skin cancer diagnosis and treatment. Identifying their mechanisms may help develop targeted therapies.","specificNumbers":"","methodology":"This is a review study analyzing existing literature on the roles of AMPs in skin cancer.","limitations":"The study is a review and relies on existing literature, which may contain conflicting results."},{"rthcId":"RPEP-06249","title":"Adiponectin, leptin, cortisol, neuropeptide Y and profile of mood states in athletes participating in an ultramarathon during winter: An observational study.","authors":"Kienast, Camilla; Biere, Katharina; Coker, Robert H; Genov, Nikolai N; Jörres, Marc; Maggioni, Martina Anna; Mascarell-Maricic, Lea; Schalt, Adriane; Genov, Magdalena; Gunga, Hanns-Christian; Steinach, Mathias","year":2022,"journal":"Frontiers in physiology, 13, 970016","doi":"10.3389/fphys.2022.970016","pmid":"36579027","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Non-finishers showed increased anger and depressive moods, while finishers had better recovery linked to neuropeptide Y.","whyItMatters":"Understanding the relationship between hormones and mood can help improve athlete performance and mental health during extreme sports. This knowledge could lead to better training and recovery strategies.","specificNumbers":"","methodology":"The study involved 36 athletes assessed at four time points during a 690 km ultramarathon, measuring hormones and mood states.","limitations":"The study's small sample size may limit the generalizability of the findings, and it was observational rather than experimental."},{"rthcId":"RPEP-06250","title":"Receptor mechanisms mediating the anti-neuroinflammatory effects of endocannabinoid system modulation in a rat model of migraine.","authors":"Kilinc, Erkan; Ankarali, Seyit; Torun, Ibrahim Ethem; Dagistan, Yasar","year":2022,"journal":"The European journal of neuroscience, 55(4), 1015-1031","doi":"10.1111/ejn.14897","pmid":"32639078","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Methanandamide reduced CGRP levels and mast cell degranulation in migraine models.","whyItMatters":"Understanding how cannabinoids modulate migraine-related inflammation could lead to new therapeutic strategies. This research highlights the potential of cannabinoid receptors as targets for migraine treatment.","specificNumbers":"","methodology":"The study used an in vivo rat model of migraine induced by nitroglycerin and ex vivo hemiskull preparations to assess the effects of cannabinoid modulation.","limitations":"The study was conducted in rats, which may limit the applicability of findings to humans. Further research is needed to confirm these effects in human subjects."},{"rthcId":"RPEP-06251","title":"Durability of glucose-lowering effect of dulaglutide in patients with type 2 diabetes mellitus: A real-world data study.","authors":"Kim, Hwi Seung; Cho, Yun Kyung; Kim, Myung Jin; Jung, Chang Hee; Park, Joong-Yeol; Lee, Woo Je","year":2022,"journal":"Frontiers in endocrinology, 13, 1032793","doi":"10.3389/fendo.2022.1032793","pmid":"36387922","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"HbA1c decreased by 1.28% and body weight by 3.19 kg over an average follow-up of 33.1 months.","whyItMatters":"Understanding the long-term effects of diabetes medications like dulaglutide can help improve treatment strategies for managing type 2 diabetes.","specificNumbers":"","methodology":"A retrospective study analyzing data from 605 participants who used dulaglutide for over one year.","limitations":"The study is retrospective and may be subject to biases inherent in such designs."},{"rthcId":"RPEP-06252","title":"Oral Supplementation of Low-Molecular-Weight Collagen Peptides Reduces Skin Wrinkles and Improves Biophysical Properties of Skin: A Randomized, Double-Blinded, Placebo-Controlled Study.","authors":"Kim, Jemin; Lee, Sang Gyu; Lee, Joohee; Choi, Sooyeon; Suk, Jangmi; Lee, Ju Hee; Yang, Joo Hwan; Yang, Joon Sung; Kim, Jihee","year":2022,"journal":"Journal of medicinal food, 25(12), 1146-1154","doi":"10.1089/jmf.2022.K.0097","pmid":"36516059","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06253","title":"Minimally invasive skin sampling and transcriptome analysis using microneedles for skin type biomarker research.","authors":"Kim, Seo Hyeong; Kim, Ji Hye; Lee, Sung Jae; Jung, Min Sook; Jeong, Do Hyeon; Lee, Kwang Hoon","year":2022,"journal":"Skin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging (ISSI), 28(2), 322-335","doi":"10.1111/srt.13135","pmid":"35007372","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Biocompatible microneedles made of sodium hyaluronate successfully collected skin specimens from 33 subjects for full transcriptome analysis. The researchers identified specific gene biomarkers correlating with five skin conditions: COL1A1, FN1, and PINK1 for skin aging; FLG, KLF4, and LOR for hydration; GPNMB, MLANA, and TYR for pigmentation; IGF1, MPZL3, and AQP3 for oily skin; and PGF, CYR61, RBP4, TAC1, CAMP (cathelicidin antimicrobial peptide), MMP9, MMP3, MMP12, and CCR1 for sensitive skin. The biomarkers correlated with age, device measurements, lactic acid stinging test scores, and visual assessments.","whyItMatters":"Getting accurate genetic information from skin normally requires a biopsy — an invasive procedure that leaves a wound. This study demonstrates that dissolving microneedles can collect enough RNA for comprehensive gene analysis, opening the door to painless, office-based skin diagnostics. The peptide connection is notable: cathelicidin (CAMP/LL-37), an antimicrobial peptide, emerged as a biomarker for sensitive skin, and IGF-1 (a peptide growth factor) was linked to oily skin.","specificNumbers":"n=33 subjects · 5 skin types assessed · Hyaluronate microneedles · Full microarray transcriptome · Multiple biomarkers per skin type","methodology":"33 subjects with varying skin conditions (aging, dryness, pigmentation, oiliness, sensitivity) were recruited. Skin types were classified using age, non-invasive measurement devices, a 10% lactic acid stinging test, and visual acne assessment. Skin specimens were collected from the face using biocompatible sodium hyaluronate microneedles. Total RNA was extracted and analyzed using microarray-based transcriptome profiling. Correlations between gene expression biomarkers and skin condition parameters were calculated.","limitations":"Small sample of 33 subjects limits statistical power and generalizability across diverse skin types and ethnicities. The microneedle sampling depth may differ from deeper skin biopsies, potentially missing dermal biomarkers. No comparison to traditional biopsy was included to validate equivalence. The identified biomarkers need replication in larger cohorts."},{"rthcId":"RPEP-06254","title":"An Octopus-Derived Peptide with Antidiuretic Activity in Rats.","authors":"Kim, Ye-Ji; Lee, Jei Ha; Jung, Seung-Hyun; Kim, Ki Hyun; Choi, Chang-Hoon; Jo, Seonmi; Woo, Dong Ho","year":2022,"journal":"Marine drugs, 20(5)","doi":"10.3390/md20050328","pmid":"35621979","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CPT reduced urine output and increased urinary osmolality in rats after a single injection.","whyItMatters":"Finding new, effective treatments for urological issues is crucial, and CPT could offer a natural alternative to synthetic drugs.","specificNumbers":"","methodology":"The study involved testing the peptides on human receptor-overexpressing cells and conducting animal trials in rats.","limitations":"The study was conducted in rats, and results may not directly translate to humans."},{"rthcId":"RPEP-06255","title":"Minimally invasive, sustained-release relaxin-2 microparticles reverse arthrofibrosis.","authors":"Kirsch, Jack R; Williamson, Amanda K; Yeritsyan, Diana; Blessing, William A; Momenzadeh, Kaveh; Leach, Todd R; Williamson, Patrick M; Korunes-Miller, Jenny T; DeAngelis, Joseph P; Zurakowski, David; Nazarian, Rosalynn M; Rodriguez, Edward K; Nazarian, Ara; Grinstaff, Mark W","year":2022,"journal":"Science translational medicine, 14(666), eabo3357","doi":"10.1126/scitranslmed.abo3357","pmid":"36223449","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06256","title":"Translational studies of adrenomedullin and related peptides regarding cardiovascular diseases.","authors":"Kita, Toshihiro; Kitamura, Kazuo","year":2022,"journal":"Hypertension research : official journal of the Japanese Society of Hypertension, 45(3), 389-400","doi":"10.1038/s41440-021-00806-y","pmid":"34992239","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"AM levels increase during inflammation but are less significant in CVDs; AM's half-life is under 30 minutes.","whyItMatters":"Understanding the role of AM in cardiovascular health could lead to better treatment options. The development of longer-lasting AM derivatives may enhance therapeutic applications.","specificNumbers":"","methodology":"The study is a review of existing research on adrenomedullin and its derivatives in relation to cardiovascular diseases.","limitations":"The short half-life of AM limits its therapeutic use, and early human studies have not been successful for CVD applications."},{"rthcId":"RPEP-06257","title":"Next generation GLP-1/GIP/glucagon triple agonists normalize body weight in obese mice.","authors":"Knerr, Patrick J; Mowery, Stephanie A; Douros, Jonathan D; Premdjee, Bhavesh; Hjøllund, Karina Rahr; He, Yantao; Kruse Hansen, Ann Maria; Olsen, Anette K; Perez-Tilve, Diego; DiMarchi, Richard D; Finan, Brian","year":2022,"journal":"Molecular metabolism, 63, 101533","doi":"10.1016/j.molmet.2022.101533","pmid":"35809773","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Optimized triagonists normalized body weight in DIO mice and enhanced energy expenditure more than GLP-1R mono-agonists.","whyItMatters":"This research highlights a promising approach to obesity treatment by targeting multiple hormonal pathways. Understanding how these peptides work could lead to more effective therapies for weight management.","specificNumbers":"","methodology":"The study involved designing unimolecular peptide triagonists and testing their effects on weight, food intake, glucose control, and energy expenditure in diet-induced obese (DIO) mice.","limitations":"The study is based on preclinical models, so results may not directly translate to humans."},{"rthcId":"RPEP-06258","title":"Substance P, A Promising Therapeutic Target in Musculoskeletal Disorders.","authors":"Ko, Kyung Rae; Lee, Hyunil; Han, Soo-Hong; Ahn, Wooyeol; Kim, Do Kyung; Kim, Il-Su; Jung, Bo Sung; Lee, Soonchul","year":2022,"journal":"International journal of molecular sciences, 23(5)","doi":"10.3390/ijms23052583","pmid":"35269726","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"SP combined with an adequate conjugate may be a regenerative option for osteoarthritis.","whyItMatters":"Understanding the SP-NK1R pathway could lead to new treatments for common musculoskeletal issues, improving patient outcomes.","specificNumbers":"","methodology":"This is a review of existing studies on the SP-NK1R pathway in musculoskeletal disorders.","limitations":"As a review, it summarizes existing studies but does not present new experimental data."},{"rthcId":"RPEP-06259","title":"Substance P Inhibitor Promotes Tendon Healing in a Collagenase-Induced Rat Model of Tendinopathy.","authors":"Ko, Kyung Rae; Han, Soo-Hong; Choi, Sujin; An, Hyun-Ju; Kwak, Eun-Bee; Jeong, Yunhui; Baek, Minjung; Lee, Jusung; Choi, Junwon; Kim, Il-Su; Lee, Soonchul","year":2022,"journal":"The American journal of sports medicine, 50(13), 3681-3689","doi":"10.1177/03635465221126175","pmid":"36197354","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The SPI group showed significantly greater tensile strength compared to the tendinopathy group.","whyItMatters":"These findings indicate that targeting the substance P pathway may offer a new approach to treating tendon injuries, potentially improving recovery outcomes.","specificNumbers":"","methodology":"The study involved in vitro analysis of inflamed tenocytes and a collagenase-induced rat model of tendinopathy, with various tests to assess healing.","limitations":"The study was conducted in rats, and results may not directly translate to human patients."},{"rthcId":"RPEP-06260","title":"Top-Down Glycopeptidomics Reveals Intact Glycomacropeptide Is Digested to a Wide Array of Peptides in Human Jejunum.","authors":"Koh, Jeewon; Kim, Bum Jin; Qu, Yunyao; Huang, Honggang; Dallas, David C","year":2022,"journal":"The Journal of nutrition, 152(2), 429-438","doi":"10.1093/jn/nxab400","pmid":"34850069","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Intact CMP accounted for 90% of the total ion abundance in the feed but less than 2% in jejunal fluids.","whyItMatters":"Understanding how CMP is digested can help in assessing its potential health benefits and bioactivity in humans. This knowledge could inform dietary recommendations and product development.","specificNumbers":"","methodology":"Three healthy adults consumed 37.5 g of purified CMP, and jejunal fluids were collected over 3 hours for analysis.","limitations":"The study had a small sample size of only three participants, which may limit the generalizability of the findings."},{"rthcId":"RPEP-06261","title":"An M protein coiled coil unfurls and exposes its hydrophobic core to capture LL-37.","authors":"Kolesinski, Piotr; Wang, Kuei-Chen; Hirose, Yujiro; Nizet, Victor; Ghosh, Partho","year":2022,"journal":"eLife, 11","doi":"10.7554/eLife.77989","pmid":"35726694","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The M87 protein captures LL-37 by exposing its hydrophobic core, contributing to LL-37 resistance.","whyItMatters":"Understanding how M proteins neutralize LL-37 can inform the development of new treatments for infections caused by Streptococcus pyogenes.","specificNumbers":"","methodology":"The study used X-ray crystallography to analyze the structure of the M87 protein in complex with LL-37.","limitations":"The study primarily focuses on one variant of M protein and may not fully represent all strains."},{"rthcId":"RPEP-06262","title":"Glucagon-like peptide-1 (GLP-1) receptor agonists and neuroinflammation: Implications for neurodegenerative disease treatment.","authors":"Kopp, Katherine O; Glotfelty, Elliot J; Li, Yazhou; Greig, Nigel H","year":2022,"journal":"Pharmacological research, 186, 106550","doi":"10.1016/j.phrs.2022.106550","pmid":"36372278","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 receptor agonists may effectively target neuroinflammation associated with Alzheimer's and Parkinson's diseases.","whyItMatters":"Targeting neuroinflammation could provide new treatment avenues for neurodegenerative diseases, which currently have limited options. Repurposing existing drugs may offer a safer and more cost-effective solution.","specificNumbers":"","methodology":"The study is a review of existing literature on GLP-1 receptor agonists and their effects on neuroinflammation and neurodegenerative diseases.","limitations":"The review does not include new experimental data and relies on existing studies, which may vary in quality and relevance."},{"rthcId":"RPEP-06263","title":"The dual neural effects of oxytocin in autistic youth: results from a randomized trial.","authors":"Korisky, Adi; Goldstein, Abraham; Gordon, Ilanit","year":2022,"journal":"Scientific reports, 12(1), 16304","doi":"10.1038/s41598-022-19524-7","pmid":"36175473","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Oxytocin increased M170 activity in frontal regions for social stimuli in autistic adolescents.","whyItMatters":"Understanding how oxytocin influences social perception could lead to new therapeutic approaches for autistic individuals. This research contributes to the growing body of knowledge on the neural mechanisms underlying social behavior.","specificNumbers":"","methodology":"The study used a randomized, double-blind design with MEG to assess brain activity after administering oxytocin or placebo.","limitations":"The study had a small sample size and focused only on adolescents, which may limit generalizability."},{"rthcId":"RPEP-06264","title":"CCR6 activation links innate immune responses to mucosa-associated lymphoid tissue lymphoma development.","authors":"Korona, Boguslawa; Korona, Dagmara; Zhao, Wanfeng; Wotherspoon, Andrew C; Du, Ming-Qing","year":2022,"journal":"Haematologica, 107(6), 1384-1396","doi":"10.3324/haematol.2021.280067","pmid":"35142152","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CCR6 mutations impair receptor internalization and enhance apoptosis resistance, malignant transformation, and migration.","whyItMatters":"Understanding CCR6's role in lymphoma can inform new therapeutic strategies and improve patient outcomes. It also sheds light on how immune responses contribute to cancer development.","specificNumbers":"","methodology":"The study involved analyzing CCR6 mutations and their effects on receptor signaling in malignant B cells.","limitations":"The study primarily focuses on cellular mechanisms and may not fully capture the complexity of MALT lymphoma in vivo."},{"rthcId":"RPEP-06265","title":"Role of Substance P-Dependent Chemotactic Signaling in Postoperative Adhesion Formation.","authors":"Kosaka, Hisashi; Kaibori, Masaki; Chu, Daniel I; Stucchi, Arthur F; Sekimoto, Mitsugu","year":2022,"journal":"The Journal of surgical research, 270, 49-57","doi":"10.1016/j.jss.2021.08.038","pmid":"34638093","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Blocking substance P and CXCR2 reduced postsurgical adhesion formation.","whyItMatters":"Understanding the mechanisms behind adhesion formation can help develop better treatments to prevent this complication after surgery, potentially improving patient outcomes.","specificNumbers":"","methodology":"The study utilized a mouse model of cecal cauterization to simulate abdominal surgery and measured various protein and mRNA levels in response to specific antagonists.","limitations":"The study was conducted in mice, and results may not directly translate to humans."},{"rthcId":"RPEP-06266","title":"Therapies targeting CGRP signaling for medication overuse headache.","authors":"Koumprentziotis, Ioannis-Alexios; Mitsikostas, Dimos D","year":2022,"journal":"Current opinion in neurology, 35(3), 353-359","doi":"10.1097/WCO.0000000000001061","pmid":"35674079","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Patients with MOH benefit from anti-CGRP mAbs treatment over placebo, as shown in phase-3 trials.","whyItMatters":"Finding effective treatments for MOH is crucial due to its high prevalence and impact on quality of life. Anti-CGRP mAbs may offer a targeted therapy option.","specificNumbers":"","methodology":"The review analyzed phase-3 trial data and real-world studies regarding anti-CGRP mAbs for chronic migraine prevention in patients with MOH.","limitations":"Most trials evaluated treatments in patients with chronic migraine with MO, not exclusively in MOH patients."},{"rthcId":"RPEP-06267","title":"Synthesis and Evaluation of Two Long-Acting SSTR2 Antagonists for Radionuclide Therapy of Neuroendocrine Tumors.","authors":"Koustoulidou, Sofia; Handula, Maryana; de Ridder, Corrina; Stuurman, Debra; Beekman, Savanne; de Jong, Marion; Nonnekens, Julie; Seimbille, Yann","year":2022,"journal":"Pharmaceuticals (Basel, Switzerland), 15(9)","doi":"10.3390/ph15091155","pmid":"36145375","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Two JR11 analogs (8a and 8b) carrying albumin-binding domains were synthesized and labeled with lutetium-177 for radionuclide therapy evaluation:\n\n- Both achieved >97% radiochemical purity and >95% stability in PBS and mouse serum\n- 8a showed better human albumin binding affinity than 8b\n- Both analogs had significantly lower SSTR2 binding affinity than parent JR11 (30-fold and 48-fold lower, respectively)\n- Both showed high cell uptake but low internalization rate (consistent with antagonist behavior)\n- SPECT/CT imaging showed high tumor accumulation for [177Lu]Lu-8a at 4, 24, 48, and 72 hours post-injection, comparable to JR11\n- [177Lu]Lu-8b showed no tumor uptake despite in vitro activity\n- Ex vivo biodistribution revealed increasing tumor uptake over time for 8a, but its extended blood circulation resulted in an unfavorable biodistribution profile for therapeutic use","whyItMatters":"Peptide receptor radionuclide therapy (PRRT) is an established treatment for neuroendocrine tumors, but optimizing peptide pharmacokinetics remains critical. While longer blood circulation could increase radiation delivered to tumors, this study reveals the trade-off: extended circulation also increases radiation to healthy tissues. Finding the right balance is essential for making safer, more effective radioactive cancer treatments.","specificNumbers":"","methodology":"Researchers designed and synthesized two JR11 peptide analogs incorporating albumin-binding domains. Both were radiolabeled with lutetium-177 and characterized for radiochemical purity and stability. In vitro assays measured albumin binding, SSTR2 affinity, cell uptake, and internalization. In vivo SPECT/CT imaging tracked tumor accumulation over 72 hours in tumor-bearing mice. Ex vivo biodistribution studies quantified organ-level uptake to assess therapeutic suitability.","limitations":"Both analogs showed substantially reduced SSTR2 binding affinity compared to the parent peptide JR11, which may limit therapeutic efficacy. One analog (8b) showed no tumor uptake in vivo despite in vitro activity, highlighting the gap between bench and in vivo performance. The study was preclinical (mouse models only). The unfavorable biodistribution of 8a means neither analog is suitable for clinical development in its current form."},{"rthcId":"RPEP-06268","title":"Teriparatide and Osteosarcoma Risk: History, Science, Elimination of Boxed Warning, and Other Label Updates.","authors":"Krege, John H; Gilsenan, Alicia W; Komacko, John L; Kellier-Steele, Nicole","year":2022,"journal":"JBMR plus, 6(9), e10665","doi":"10.1002/jbm4.10665","pmid":"36111201","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06269","title":"Review of Novel Potential Insulin Resistance Biomarkers in PCOS Patients-The Debate Is Still Open.","authors":"Kruszewska, Jagoda; Laudy-Wiaderny, Hanna; Kunicki, Michał","year":2022,"journal":"International journal of environmental research and public health, 19(4)","doi":"10.3390/ijerph19042099","pmid":"35206286","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06270","title":"Brazilian descriptive study of 104 consecutive real-world migraine patients treated with monoclonal antibodies.","authors":"Krymchantowski, Abouch; Silva-Néto, Raimundo Pereira; Jevoux, Carla; Krymchantowski, Ana Gabriela","year":2022,"journal":"Postgraduate medicine, 134(6), 598-602","doi":"10.1080/00325481.2022.2080381","pmid":"35584542","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"57.7% of patients had over 50% reduction in headache attacks after 3 months.","whyItMatters":"This research provides valuable insights into the effectiveness of monoclonal antibodies for treating migraines in a real-world setting, which can guide clinical practice.","specificNumbers":"","methodology":"An observational, prospective, uncontrolled study involving 112 migraine patients treated with monoclonal antibodies.","limitations":"The study was uncontrolled and observational, which may limit the ability to draw causal conclusions."},{"rthcId":"RPEP-06271","title":"Development of Macrocyclic PRMT5-Adaptor Protein Interaction Inhibitors.","authors":"Krzyzanowski, Adrian; Esser, Lea Marie; Willaume, Anthony; Prudent, Renaud; Peter, Christoph; 't Hart, Peter; Waldmann, Herbert","year":2022,"journal":"Journal of medicinal chemistry, 65(22), 15300-15311","doi":"10.1021/acs.jmedchem.2c01273","pmid":"36378254","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The cyclic PRMT5 binding peptide has a Ki of 66 nM and an IC50 of 654 nM against specific adaptor proteins.","whyItMatters":"Targeting PRMT5 interactions could lead to new cancer therapies, as it plays a crucial role in substrate selectivity. This research provides a foundation for developing more effective treatments.","specificNumbers":"","methodology":"The study involved designing and synthesizing macrocyclic peptides, screening a peptide library, and analyzing the binding affinities of the inhibitors.","limitations":"The study primarily focuses on in vitro results, which may not fully translate to in vivo efficacy or human applications."},{"rthcId":"RPEP-06272","title":"Inhibition of SARS-CoV-2 Infection by Human Defensin HNP1 and Retrocyclin RC-101.","authors":"Kudryashova, Elena; Zani, Ashley; Vilmen, Geraldine; Sharma, Amit; Lu, Wuyuan; Yount, Jacob S; Kudryashov, Dmitri S","year":2022,"journal":"Journal of molecular biology, 434(6), 167225","doi":"10.1016/j.jmb.2021.167225","pmid":"34487793","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"HNP1 bound to the SARS-CoV-2 Spike protein with submicromolar affinity — more than 20-fold stronger than its binding to serum albumin. Both HNP1 (an α-defensin) and retrocyclin RC-101 (a θ-defensin) interfered with Spike-mediated membrane fusion, Spike-pseudotyped lentivirus infection, and authentic SARS-CoV-2 infection in cell culture.\n\nThe mechanism involves defensins destabilizing and precipitating the Spike protein and inhibiting its interaction with the ACE2 receptor — the cellular entry point for SARS-CoV-2. This correlates with the known ability of defensins to unfold proteins with high conformational plasticity.\n\nSerum reduced the antiviral activity of HNP1, likely due to competitive binding with serum proteins. However, at high concentrations, HNP1 still inactivated the virus even in serum, suggesting physiologically relevant antiviral potential.","whyItMatters":"Understanding how the body's own antimicrobial peptides fight SARS-CoV-2 illuminates natural defense mechanisms that work regardless of viral variants. Unlike vaccines and antibodies that target specific Spike protein sequences, defensins work by physically destabilizing the protein structure — a mechanism that could remain effective against future variants. This knowledge could inform the development of defensin-based antiviral therapies or nasal sprays for infection prevention.","specificNumbers":"","methodology":"The researchers used multiple in vitro assays: binding affinity measurements between defensins and Spike protein, Spike-mediated membrane fusion assays, Spike-pseudotyped lentivirus infection assays, and authentic SARS-CoV-2 infection experiments in cell culture. They tested the effects with and without serum to assess physiological relevance. Protein destabilization and precipitation assays characterized the mechanism of Spike inactivation.","limitations":"All experiments were conducted in cell culture — in vivo antiviral efficacy in animals or humans has not been tested. Serum significantly reduced HNP1 activity, raising questions about whether physiological concentrations in the respiratory tract are sufficient for meaningful antiviral effects. The study does not address defensin stability in the airways or potential toxicity at the high concentrations needed to overcome serum inhibition. Only two defensins were tested against one virus strain."},{"rthcId":"RPEP-06273","title":"In Silico Design of Chemically Modified Cell-Penetrating Peptides.","authors":"Kumar, Vinod; Raghava, Gajendra P S","year":2022,"journal":"Methods in molecular biology (Clifton, N.J.), 2383, 63-71","doi":"10.1007/978-1-0716-1752-6_4","pmid":"34766282","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CellPPDMod can predict the cell-penetration potential of modified peptides.","whyItMatters":"Improving the design of CPPs can lead to more effective drug delivery systems, enhancing treatment outcomes. This research addresses key limitations of existing peptides.","specificNumbers":"","methodology":"The study involved the development of an in silico tool for predicting CPP effectiveness.","limitations":"The study primarily discusses theoretical predictions and lacks experimental validation of the modified peptides."},{"rthcId":"RPEP-06274","title":"Studying the Rationale of Fire Ant Sting Therapy Usage by the Tribal Natives of Bastar Revealed Ant Venom-Derived Peptides with Promising Anti-Malarial Activity.","authors":"Kumari, Jyoti; Sah, Raj Kumar; Mohaideen S, Nazar Mohamed; Ahmad, Shakeel; Pati, Soumya; Singh, Shailja","year":2022,"journal":"Toxins, 14(11)","doi":"10.3390/toxins14110789","pmid":"36422964","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Fire ant venom peptides significantly reduced Plasmodium falciparum growth in vitro.","whyItMatters":"With rising drug resistance in malaria, exploring natural therapies like fire ant venom could lead to new treatment options. This research opens avenues for developing effective anti-malarial drugs from natural sources.","specificNumbers":"","methodology":"The study involved extracting venom peptides from fire ants and testing their anti-malarial effects in vitro and in infected mice models.","limitations":"The study primarily focused on in vitro and animal models, which may not fully represent human responses."},{"rthcId":"RPEP-06275","title":"In silico analysis of kiss2, expression studies and protein-protein interaction with gonadotropin-releasing hormone 2 (GnRH2) and luteinizing hormone beta (LHβ) in Heteropneustes fossilis.","authors":"Kumari, Pooja; Kumar, Mohit; Sehgal, Neeta; Aggarwal, Neerja","year":2022,"journal":"Journal of biomolecular structure & dynamics, 40(10), 4543-4557","doi":"10.1080/07391102.2020.1860820","pmid":"33345697","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Kiss2 protein shows the highest interaction with kisspeptin receptor 2.","whyItMatters":"Understanding kiss2's interactions can provide insights into reproductive biology and developmental processes in fish, which may have broader implications for aquaculture and conservation.","specificNumbers":"","methodology":"The study utilized in silico analysis, including molecular docking and structural modeling of the kiss2 protein.","limitations":"The study relies on computational methods, which may not fully replicate in vivo conditions."},{"rthcId":"RPEP-06276","title":"Aberrant Expression of Thymosin Beta-4 Correlates With Advanced Disease and BRAF V600E Mutation in Thyroid Cancer.","authors":"Kuo, Chi-Yu; Jhuang, Jie-Yang; Huang, Wen-Chien; Cheng, Shih-Ping","year":2022,"journal":"The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society, 70(10), 707-716","doi":"10.1369/00221554221138370","pmid":"36321670","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Immunohistochemical analysis showed that normal thyroid tissue and benign thyroid disorders had virtually undetectable thymosin beta-4 (TMSB4X), with the exception of inflammatory cells in autoimmune thyroid disease. In contrast, TMSB4X was overexpressed across all thyroid cancer types examined: papillary, follicular, poorly differentiated, and undifferentiated.\n\nAmong 141 patients with differentiated thyroid cancer, higher TMSB4X expression was significantly associated with papillary tumor type, extrathyroidal extension (cancer growing beyond the thyroid gland), lymph node metastasis, and the presence of the BRAF V600E mutation. These findings were validated against public transcriptomic datasets.","whyItMatters":"Thyroid cancer is the most common endocrine malignancy, and identifying markers that distinguish aggressive from indolent disease is a major clinical priority. The BRAF V600E mutation is already used to guide treatment decisions, and the discovery that thymosin beta-4 may be a downstream effector of this mutation adds a new layer of understanding. If validated, TMSB4X could help pathologists assess cancer aggressiveness and potentially serve as a target for new therapies.","specificNumbers":"","methodology":"The researchers performed immunohistochemical staining for thymosin beta-4 on thyroid tissue samples from patients with benign conditions and various types of thyroid cancer. They analyzed 141 patients with differentiated thyroid cancer to correlate TMSB4X expression levels with clinical and pathological features. Results were cross-validated using publicly available gene expression databases from prior single-cell RNA sequencing studies.","limitations":"The study is observational and demonstrates correlation, not causation — it cannot prove that thymosin beta-4 drives cancer progression. The analysis is limited to immunohistochemistry and does not include functional experiments to determine TMSB4X's biological role in thyroid cancer cells. The sample size of 141 patients, while reasonable, may not capture the full spectrum of thyroid cancer behavior. The study does not assess whether TMSB4X levels predict patient outcomes like recurrence or survival."},{"rthcId":"RPEP-06277","title":"Anxiety and Depression: What Do We Know of Neuropeptides?","authors":"Kupcova, Ida; Danisovic, Lubos; Grgac, Ivan; Harsanyi, Stefan","year":2022,"journal":"Behavioral sciences (Basel, Switzerland), 12(8)","doi":"10.3390/bs12080262","pmid":"36004833","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies multiple neuropeptide systems implicated in anxiety and depression: oxytocin (anxiolytic and antidepressant properties), vasopressin (stress response regulation), neuropeptide Y (stress resilience and anti-anxiety effects), neuropeptide S (anxiolytic potential), and Substance P (pro-anxiety and pro-depressive when elevated, with NK1 antagonists showing antidepressant effects).\n\nMany neuropeptides act as neuromodulators co-released with classical neurotransmitters, enabling communication between brain and body. The review notes that novel neuropeptides are increasingly being identified as having implications for mood disorder research, expanding the pool of potential therapeutic targets beyond traditional neurotransmitter-based approaches.","whyItMatters":"Depression and anxiety are among the most common mental health conditions worldwide, yet current medications are inadequate for many patients. Neuropeptides represent a fundamentally different class of targets from traditional neurotransmitter-based drugs. Understanding their roles could lead to entirely new classes of psychiatric medications with different mechanisms of action and potentially better outcomes for treatment-resistant patients.","specificNumbers":"","methodology":"Comprehensive narrative review of published research on neuropeptides in anxiety and depression, covering both human and animal model studies. The authors examined neuropeptide pathways, roles in stress adaptation, and the etiology of mood disorders, with a focus on the latest research findings and emerging neuropeptide targets.","limitations":"This is a review article that synthesizes existing literature without presenting new experimental data. The translation from animal neuropeptide research to human psychiatric treatments has been historically challenging. Many neuropeptide-based drug candidates have failed in clinical trials despite promising preclinical data. The blood-brain barrier presents a delivery challenge for peptide-based therapies targeting brain circuits."},{"rthcId":"RPEP-06278","title":"Heterochiral tetrapeptide self-assembly into hydrogel biomaterials for hydrolase mimicry.","authors":"Kurbasic, Marina; Garcia, Ana M; Viada, Simone; Marchesan, Silvia","year":2022,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 28(1), e3304","doi":"10.1002/psc.3304","pmid":"33521995","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The peptides exhibited mild esterase-like activity in hydrogel form, but Ser did not enhance this activity.","whyItMatters":"This research contributes to the development of biomaterials that can mimic enzyme functions, which is important for various applications in biotechnology and medicine.","specificNumbers":"","methodology":"The study utilized circular dichroism, transmission electron microscopy, oscillatory rheology, and Thioflavin T fluorescence to analyze the peptides and their properties.","limitations":"The study does not explore the full range of potential applications or the long-term stability of the hydrogels."},{"rthcId":"RPEP-06279","title":"Prediction, Discovery, and Characterization of Plant- and Food-Derived Health-Beneficial Bioactive Peptides.","authors":"Kussmann, Martin","year":2022,"journal":"Nutrients, 14(22)","doi":"10.3390/nu14224810","pmid":"36432497","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Bioactive peptides from plants and foods can address chronic health issues and improve health span.","whyItMatters":"Understanding and utilizing bioactive peptides can lead to better health outcomes and more sustainable healthcare solutions. This research could pave the way for new treatments derived from natural sources.","specificNumbers":"","methodology":"The study discusses the use of systems-level approaches and AI for discovering and validating bioactive peptides.","limitations":"The study is conceptual and does not provide empirical data or specific experimental results."},{"rthcId":"RPEP-06280","title":"Substance P Serum Degradation in Complex Regional Pain Syndrome - Another Piece of the Puzzle?","authors":"König, Simone; Engl, Christian; Bayer, Malte; Escolano-Lozano, Fabiola; Rittner, Heike; Rebhorn, Cora; Birklein, Frank","year":2022,"journal":"The journal of pain, 23(3), 501-507","doi":"10.1016/j.jpain.2021.10.005","pmid":"34678467","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"SP metabolism was less efficient in CRPS and trauma control patients compared to healthy controls (P < .03).","whyItMatters":"Understanding how SP is metabolized in pain conditions could help develop better treatments for chronic pain. The findings highlight the potential impact of trauma on pain management.","specificNumbers":"","methodology":"The study involved a thin layer chromatography assay to measure SP levels in serum from 24 CRPS patients, 26 healthy controls, and 13 trauma controls.","limitations":"The study does not establish a clear clinical phenotype related to impaired SP degradation and suggests that findings may not be specific to CRPS."},{"rthcId":"RPEP-06281","title":"Hydrogelation tunability of bioinspired short peptides.","authors":"La Manna, Sara; Florio, Daniele; Panzetta, Valeria; Roviello, Valentina; Netti, Paolo Antonio; Di Natale, Concetta; Marasco, Daniela","year":2022,"journal":"Soft matter, 18(44), 8418-8426","doi":"10.1039/d2sm01385a","pmid":"36300826","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Four novel pentapeptides derived from the 269-273 fragment of nucleophosmin 1 protein were designed and characterized. Three of four peptides showed typical shear-thinning profiles (meaning they flow when pushed but re-gel when force is removed — ideal for injection-based delivery) and self-assembled into hierarchical nanostructured fibers.\n\nTwo of the four peptides were biocompatible when tested with MCF7 cells. The study revealed that the terminal groups critically modulate hydrogel properties: C-terminal amidation caused the fastest aggregation and highest content of structured intermediates during the gelling process. This demonstrates that simple modifications to peptide ends can fine-tune hydrogel behavior.","whyItMatters":"Peptide hydrogels are among the most promising biomaterials for drug delivery and tissue engineering because they're biocompatible, biodegradable, and can be designed with specific properties. Most peptide hydrogels rely on phenylalanine-driven assembly, limiting design options. This new class of Phe-free peptide hydrogels expands the design space and demonstrates that simple terminal modifications can precisely control gel properties — a level of tunability essential for customizing materials to specific biomedical applications.","specificNumbers":"","methodology":"Researchers synthesized four pentapeptide variants based on the nucleophosmin 1 protein fragment (residues 269-273) with different terminal modifications. Hydrogel formation and mechanical properties were characterized using rheology (measuring stiffness and flow). Molecular structure was analyzed by spectroscopy, and fiber morphology was visualized using scanning microscopy. Biocompatibility was tested using MCF7 (breast cancer) cell viability assays.","limitations":"Biocompatibility was tested only with MCF7 cells (breast cancer cell line), which may not represent biocompatibility with healthy tissues or other cell types. The study is entirely in vitro with no animal testing. Only four peptide variants were explored, leaving the broader design space largely uncharted. Long-term stability and degradation behavior of the hydrogels were not reported. The biomedical applications suggested are theoretical — no drug loading or delivery experiments were conducted."},{"rthcId":"RPEP-06282","title":"Thymosin β4 Is an Endogenous Iron Chelator and Molecular Switcher of Ferroptosis.","authors":"Lachowicz, Joanna I; Pichiri, Giusi; Piludu, Marco; Fais, Sara; Orrù, Germano; Congiu, Terenzio; Piras, Monica; Faa, Gavino; Fanni, Daniela; Dalla Torre, Gabriele; Lopez, Xabier; Chandra, Kousik; Szczepski, Kacper; Jaremko, Lukasz; Ghosh, Mitra; Emwas, Abdul-Hamid; Castagnola, Massimo; Jaremko, Mariusz; Hannappel, Ewald; Coni, Pierpaolo","year":2022,"journal":"International journal of molecular sciences, 23(1)","doi":"10.3390/ijms23010551","pmid":"35008976","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tβ4 inhibits ferroptosis in macrophage cells and binds to iron with four distinct regions.","whyItMatters":"Understanding how Tβ4 influences ferroptosis could lead to new therapeutic strategies for diseases like cancer and neurodegeneration.","specificNumbers":"","methodology":"The study involved extracting Tβ4 and testing its effects on ferroptosis in a macrophage cell line, analyzing gene expression changes.","limitations":"The study primarily focuses on in vitro findings, which may not fully translate to in vivo human conditions."},{"rthcId":"RPEP-06283","title":"Targeting an alternate Wilms' tumor antigen 1 peptide bypasses immunoproteasome dependency.","authors":"Lahman, Miranda C; Schmitt, Thomas M; Paulson, Kelly G; Vigneron, Nathalie; Buenrostro, Denise; Wagener, Felecia D; Voillet, Valentin; Martin, Lauren; Gottardo, Raphael; Bielas, Jason; McElrath, Julie M; Stirewalt, Derek L; Pogosova-Agadjanyan, Era L; Yeung, Cecilia C; Pierce, Robert H; Egan, Daniel N; Bar, Merav; Hendrie, Paul C; Kinsella, Sinéad; Vakil, Aesha; Butler, Jonah; Chaffee, Mary; Linton, Jonathan; McAfee, Megan S; Hunter, Daniel S; Bleakley, Marie; Rongvaux, Anthony; Van den Eynde, Benoit J; Chapuis, Aude G; Greenberg, Philip D","year":2022,"journal":"Science translational medicine, 14(631), eabg8070","doi":"10.1126/scitranslmed.abg8070","pmid":"35138909","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The new TCR (TTCR37-45) effectively killed relapsed AML cells resistant to previous targeting.","whyItMatters":"Understanding how leukemia cells evade immune targeting can lead to more effective therapies. This research opens new avenues for treating resistant forms of leukemia.","specificNumbers":"","methodology":"The study involved analyzing patient samples and testing T cell receptors in vitro and in a mouse model.","limitations":"The study primarily focuses on a small number of patients and in vitro models, which may limit generalizability."},{"rthcId":"RPEP-06284","title":"Natural and Man-Made Cyclic Peptide-Based Antibiotics.","authors":"Lai, Shian; Zhang, Quan; Jin, Lin","year":2022,"journal":"Antibiotics (Basel, Switzerland), 12(1)","doi":"10.3390/antibiotics12010042","pmid":"36671244","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Cyclic AMPs are effective against drug-resistant bacteria and have low resistance induction.","whyItMatters":"The rise of drug-resistant bacteria poses a significant threat to health, making the development of new antibiotics crucial. Cyclic AMPs could provide a viable alternative to traditional antibiotics.","specificNumbers":"","methodology":"This is a mini-review discussing existing literature on cyclic antimicrobial peptides.","limitations":"As a mini-review, it does not present original research data and relies on existing literature."},{"rthcId":"RPEP-06285","title":"Mechanistic Insights into Angiotensin I-Converting Enzyme Inhibitory Tripeptides to Decipher the Chemical Basis of Their Activity.","authors":"Lammi, Carmen; Boschin, Giovanna; Bartolomei, Martina; Arnoldi, Anna; Galaverna, Gianni; Dellafiora, Luca","year":2022,"journal":"Journal of agricultural and food chemistry, 70(37), 11572-11578","doi":"10.1021/acs.jafc.2c04755","pmid":"36074807","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"LCP was identified as a potent ACE inhibitory peptide with IC50 values of 8.25 μM (cell-free) and 6.95 μM (cell-based).","whyItMatters":"Understanding the mechanisms of these peptides can lead to the development of new treatments for hypertension, potentially improving health outcomes for many individuals.","specificNumbers":"","methodology":"The study combined computational analysis and in vitro assays to evaluate the ACE inhibitory activity of various tripeptides.","limitations":"The study primarily focused on in vitro methods, which may not fully replicate human physiological conditions."},{"rthcId":"RPEP-06286","title":"Does receptor balance matter? - Comparing the efficacies of the dual amylin and calcitonin receptor agonists cagrilintide and KBP-336 on metabolic parameters in preclinical models.","authors":"Larsen, A T; Mohamed, K E; Sonne, N; Bredtoft, E; Andersen, F; Karsdal, M A; Henriksen, K","year":2022,"journal":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 156, 113842","doi":"10.1016/j.biopha.2022.113842","pmid":"36242844","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"KBP-336 was superior to cagrilintide in inducing weight loss and improving glucose control in rats.","whyItMatters":"These findings suggest that receptor balance is crucial for the effectiveness of weight loss and diabetes treatments, potentially guiding future drug development.","specificNumbers":"","methodology":"The study involved in vitro receptor activation assays and in vivo tests on obese and diabetic rat models.","limitations":"The study was conducted in preclinical models, so results may not directly translate to humans."},{"rthcId":"RPEP-06287","title":"Substance P/neurokinin-1 receptor pathway blockade ameliorates limbal stem cell deficiency by modulating mTOR pathway and preventing cell senescence.","authors":"Lasagni Vitar, Romina; Triani, Francesca; Barbariga, Marco; Fonteyne, Philippe; Rama, Paolo; Ferrari, Giulio","year":2022,"journal":"Stem cell reports, 17(4), 849-863","doi":"10.1016/j.stemcr.2022.02.012","pmid":"35334220","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"SP ablation or NK1R blockade increased epithelial wound healing (p < 0.001) and corneal transparency (p < 0.001).","whyItMatters":"Improving healing in LSCD could enhance patient outcomes for severe ocular surface diseases. This research opens avenues for new treatments targeting the SP/NK1R pathway.","specificNumbers":"","methodology":"The study used a pre-clinical model to evaluate the effects of SP ablation and NK1R blockade on corneal epithelium wound healing.","limitations":"The study is pre-clinical, and results may not directly translate to human patients."},{"rthcId":"RPEP-06288","title":"The two-faced effects of nerves and neuropeptides in corneal diseases.","authors":"Lasagni Vitar, Romina Mayra; Rama, Paolo; Ferrari, Giulio","year":2022,"journal":"Progress in retinal and eye research, 86, 100974","doi":"10.1016/j.preteyeres.2021.100974","pmid":"34098111","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Corneal nerve injury can lead to both beneficial wound healing and detrimental vision impairment.","whyItMatters":"Understanding the balance of neurogenic inflammation can help develop better treatments for common eye diseases. This research sheds light on how nerve health is critical for maintaining vision.","specificNumbers":"","methodology":"The study is a review that discusses corneal nerve anatomy, neurochemistry, and the effects of neurogenic inflammation.","limitations":"As a review, it does not provide new experimental data but synthesizes existing knowledge."},{"rthcId":"RPEP-06289","title":"Infrequent Intranasal Oxytocin Followed by Positive Social Interaction Improves Symptoms in Autistic Children: A Pilot Randomized Clinical Trial.","authors":"Le, Jiao; Zhang, Lan; Zhao, Weihua; Zhu, Siyu; Lan, Chunmei; Kou, Juan; Zhang, Qianqian; Zhang, Yingying; Li, Qin; Chen, Zhuo; Fu, Meina; Montag, Christian; Zhang, Rong; Yang, Wenxu; Becker, Benjamin; Kendrick, Keith M","year":2022,"journal":"Psychotherapy and psychosomatics, 91(5), 335-347","doi":"10.1159/000524543","pmid":"35545057","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Oxytocin treatment led to significant improvements in ADOS-2 and SRS-2 scores (ps < 0.001).","whyItMatters":"This research is significant as it suggests a potential new treatment for social behavior issues in autism, an area with few effective interventions.","specificNumbers":"","methodology":"A pilot double-blind, randomized, crossover trial with 41 children was conducted over six weeks.","limitations":"The study is a pilot trial with a small sample size, limiting the generalizability of the findings."},{"rthcId":"RPEP-06290","title":"Optimal long peptide for flagellin-adjuvanted HPV E7 cancer vaccine to enhance tumor suppression in combination with anti-PD-1.","authors":"Lee, Hye Hwa; Hong, Seol Hee; Rhee, Joon Haeng; Lee, Shee Eun","year":2022,"journal":"Translational cancer research, 11(6), 1595-1602","doi":"10.21037/tcr-21-2798","pmid":"35836530","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"E7-LP35 vaccine showed significantly higher antitumor activity compared to E7-SP and E7-LP20 vaccines.","whyItMatters":"This research highlights the potential of combining cancer vaccines with immune checkpoint inhibitors to improve treatment outcomes. It may lead to more effective therapies for HPV-related cancers.","specificNumbers":"","methodology":"The study utilized mouse TC-1 tumor models to compare the antitumor activity of different flagellin-adjuvanted peptide vaccines.","limitations":"The study was conducted in mouse models, which may not fully translate to human responses. Further research is needed to confirm these findings in clinical settings."},{"rthcId":"RPEP-06291","title":"Comparison of ART outcome in patients with poor ovarian response according to POSEIDON criteria.","authors":"Lee, Hyun Joo; Noh, Hye Kyung; Joo, Jong Kil","year":2022,"journal":"Scientific reports, 12(1), 17723","doi":"10.1038/s41598-022-22859-w","pmid":"36271137","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06292","title":"Nuclear factor (erythroid-derived 2)-like 2 counter-regulates thymosin beta-4 expression and primary cilium formation for HeLa cervical cancer cell survival.","authors":"Lee, Jae-Wook; Thuy, Pham Xuan; Koo, Ja Hyun; Moon, Eun-Yi","year":2022,"journal":"Scientific reports, 12(1), 20170","doi":"10.1038/s41598-022-24596-6","pmid":"36424462","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Nrf2 counter-regulates TB4 expression and primary cilium formation, promoting cell survival under serum deprivation.","whyItMatters":"Understanding how cervical cancer cells adapt to nutrient deprivation can inform potential therapeutic strategies. Targeting the mechanisms involved may lead to new treatments for cervical cancer.","specificNumbers":"","methodology":"The study used RNA interference to silence TB4, immunofluorescence for cilia analysis, and various assays to measure cell viability and gene expression.","limitations":"The study primarily focuses on HeLa cells, which may not fully represent all cervical cancer types in patients."},{"rthcId":"RPEP-06293","title":"Adipose-derived stem cells decolonize skin Staphylococcus aureus by enhancing phagocytic activity of peripheral blood mononuclear cells in the atopic rats.","authors":"Lee, Jaehee; Park, Leejin; Kim, Hyeyoung; Rho, Bong-Il; Han, Rafael Taeho; Kim, Sewon; Kim, Hee Jin; Na, Heung Sik; Back, Seung Keun","year":2022,"journal":"The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology, 26(4), 287-295","doi":"10.4196/kjpp.2022.26.4.287","pmid":"35766006","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"ASCs reduced skin colonization by S. aureus and improved dermatitis scores in AD rats.","whyItMatters":"This research highlights a potential therapeutic use of stem cells in treating atopic dermatitis, which is often complicated by skin infections. Improving immune function could lead to better management of this common skin condition.","specificNumbers":"","methodology":"The study involved inducing AD in neonatal rats and administering ASCs weekly for one month to assess their effects on immune response and skin health.","limitations":"The study was conducted in rats, so results may not directly translate to humans. Further research is needed to confirm these findings in clinical settings."},{"rthcId":"RPEP-06294","title":"A Genomics-Based Semirational Approach for Expanding the Postbiotic Potential of Collagen Peptides Using Lactobacillaceae.","authors":"Lee, Ji-Young; Hwang, Hye Won; Jin, Hyeon-Su; Lee, Jae-Eun; Kang, Nam Joo; Lee, Dong-Woo","year":2022,"journal":"Journal of agricultural and food chemistry, 70(27), 8365-8376","doi":"10.1021/acs.jafc.2c01251","pmid":"35758868","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Collagen peptides from Lacticaseibacillus paracasei exhibited activities toward GPR35, suggesting gut repair potential.","whyItMatters":"This research highlights the potential of using probiotics to enhance the health benefits of collagen, which could lead to new dietary supplements for gut health.","specificNumbers":"","methodology":"The study employed in silico digestion and anaerobic digestion with Lactobacillaceae species, followed by mass spectrometry analysis.","limitations":"The study primarily focused on in vitro methods, which may not fully translate to human gut health outcomes."},{"rthcId":"RPEP-06295","title":"Novel human skin surface antimicrobial peptide quantification method using a skin patch test chamber: A pilot study.","authors":"Lee, Jinyong; Kwon, Oh Sun; Shim, Yu Mi; Kim, Sang Kyung; Jeong, Eui Taek; Lim, Jun Man; Park, Sun Gyoo","year":2022,"journal":"Journal of cosmetic dermatology, 21(11), 6243-6248","doi":"10.1111/jocd.15227","pmid":"35816391","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The skin patch test showed a Pearson's correlation coefficient of 0.640 with tape stripping, indicating a moderate agreement.","whyItMatters":"This new method could improve the assessment of skin health and immunity without causing harm, which is particularly important for sensitive populations.","specificNumbers":"","methodology":"The study involved skin patch testing on 13 healthy subjects to measure hBD levels and compared results with the tape stripping method.","limitations":"The study had a small sample size and was a pilot study, limiting the generalizability of the findings."},{"rthcId":"RPEP-06296","title":"Development and approval of rybelsus (oral semaglutide): ushering in a new era in peptide delivery.","authors":"Lewis, Andrew L; McEntee, Nicholas; Holland, Justin; Patel, Asma","year":2022,"journal":"Drug delivery and translational research, 12(1), 1-6","doi":"10.1007/s13346-021-01000-w","pmid":"34024013","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Rybelsus (oral semaglutide) was approved by the FDA, EMA, and PMDA following the PIONEER clinical program of ten Phase 3 randomized trials. The tablet formulation demonstrated comparable efficacy to injectable semaglutide for blood glucose lowering and weight loss, and superior efficacy compared to competitor products.\n\nThe key enabling technology was Emisphere's Eligen platform, which uses the absorption enhancer SNAC (sodium N-[8-(2-hydroxybenzoyl) amino] caprylate) to facilitate transepithelial absorption of the peptide from the stomach. This represented over 30 years of research and development to overcome the fundamental barriers to oral peptide delivery: gastrointestinal degradation, poor membrane permeability, and variable pharmacokinetics.","whyItMatters":"For decades, the oral delivery of therapeutic peptides was considered one of the great unsolved problems in pharmaceutical science. Most patients strongly prefer pills over injections, and poor adherence to injectable medications is a major barrier in diabetes care. Rybelsus proved that oral peptide delivery is commercially viable and clinically effective, opening a new frontier for the entire peptide therapeutics field — not just GLP-1 drugs.","specificNumbers":"","methodology":"This is an editorial/review article (described as an \"Inspirational Note\") summarizing the publicly available research, development history, and clinical evidence behind Rybelsus. It draws on the PIONEER clinical trial program (10 Phase 3 RCTs) and the broader scientific literature on oral peptide delivery.","limitations":"This is an editorial commentary, not a primary research study or systematic review. It focuses on the development narrative and commercial potential rather than providing detailed clinical data or safety analysis. Long-term real-world outcomes and head-to-head comparisons with newer agents (like tirzepatide) are not addressed. The oral formulation requires specific dosing conditions (fasting, limited water) that may affect real-world adherence."},{"rthcId":"RPEP-06297","title":"Plasma protein binding prediction focusing on residue-level features and circularity of cyclic peptides by deep learning.","authors":"Li, Jianan; Yanagisawa, Keisuke; Yoshikawa, Yasushi; Ohue, Masahito; Akiyama, Yutaka","year":2022,"journal":"Bioinformatics (Oxford, England), 38(4), 1110-1117","doi":"10.1093/bioinformatics/btab726","pmid":"34849593","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CycPeptPPB achieved a mean absolute error (MAE) of 4.79% and a correlation coefficient (R) of 0.92.","whyItMatters":"Accurate predictions of plasma protein binding can enhance the drug discovery process for cyclic peptides, which have unique therapeutic potentials. This method could lead to better drug design and efficacy.","specificNumbers":"","methodology":"The study used deep learning to develop a prediction method that analyzes residue-level features and circularity in cyclic peptides.","limitations":"The study's predictions are based on a specific dataset, which may not encompass all cyclic peptides. Further validation in diverse biological contexts is needed."},{"rthcId":"RPEP-06298","title":"Hempseed (Cannabis sativa) Peptide H3 (IGFLIIWV) Exerts Cholesterol-Lowering Effects in Human Hepatic Cell Line.","authors":"Li, Jianqiang; Bollati, Carlotta; Bartolomei, Martina; Mazzolari, Angelica; Arnoldi, Anna; Vistoli, Giulio; Lammi, Carmen","year":2022,"journal":"Nutrients, 14(9)","doi":"10.3390/nu14091804","pmid":"35565772","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Peptide H3 inhibited HMGCoAR activity with an IC50 of 59 μM and increased LDLR levels in HepG2 cells.","whyItMatters":"Understanding how peptide H3 lowers cholesterol could lead to new dietary supplements for preventing cardiovascular diseases.","specificNumbers":"","methodology":"The study used human hepatic HepG2 cells to assess the effects of peptide H3 on cholesterol metabolism and related pathways.","limitations":"The study was conducted in vitro, so results may not directly translate to human health outcomes."},{"rthcId":"RPEP-06299","title":"Serum levels of ghrelin and LEAP2 in patients with type 2 diabetes mellitus: correlation with circulating glucose and lipids.","authors":"Li, Jiaxi; Huang, Pu; Xiong, Jing; Liang, Xinyue; Li, Mei; Ke, Hao; Chen, Chunli; Han, Yang; Huang, Yanhong; Zhou, Yan; Luo, Ziqiang; Feng, Dandan; Chen, Chen","year":2022,"journal":"Endocrine connections, 11(5)","doi":"10.1530/EC-22-0012","pmid":"35521798","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"T2D patients had lower ghrelin levels (compared to healthy adults) and higher LEAP2 levels, with ghrelin/LEAP2 ratio negatively correlated with glucose and HbA1c.","whyItMatters":"Understanding the hormonal changes in T2D can help in developing better management strategies for the disease. The findings suggest that LEAP2 may play a role in T2D development and glycemic control.","specificNumbers":"","methodology":"The study involved a cross-sectional cohort of 29 T2D patients and 27 healthy adults, measuring fasting serum levels of ghrelin and LEAP2.","limitations":"The study had a small sample size and was cross-sectional, limiting causal inferences."},{"rthcId":"RPEP-06300","title":"Preliminary Clinical Application of RGD-Containing Peptides as PET Radiotracers for Imaging Tumors.","authors":"Li, Li; Chen, Xiaoyuan; Yu, Jinming; Yuan, Shuanghu","year":2022,"journal":"Frontiers in oncology, 12, 837952","doi":"10.3389/fonc.2022.837952","pmid":"35311120","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06301","title":"Tailored Extracellular Vesicles: Novel Tool for Tissue Regeneration.","authors":"Li, Linli; Wu, Peipei; Qian, Hui; Xu, Wenrong; Shi, Hui; Jiang, Jiajia","year":2022,"journal":"Stem cells international, 2022, 7695078","doi":"10.1155/2022/7695078","pmid":"35915850","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Engineered EVs can significantly improve therapeutic efficacy and targeting for tissue regeneration.","whyItMatters":"Improving the effectiveness of EVs could lead to better treatments for tissue injuries, potentially transforming regenerative medicine. This research highlights the importance of innovation in therapeutic delivery systems.","specificNumbers":"","methodology":"The study reviews recent developments in the engineering of extracellular vesicles and their applications in tissue regeneration.","limitations":"The study primarily focuses on theoretical advancements and does not present clinical trial data or real-world applications."},{"rthcId":"RPEP-06302","title":"Substance P promotes the progression of bronchial asthma through activating the PI3K/AKT/NF-κB pathway mediated cellular inflammation and pyroptotic cell death in bronchial epithelial cells.","authors":"Li, Miao; Zhong, Xiao; Xu, Wen-Ting","year":2022,"journal":"Cell cycle (Georgetown, Tex.), 21(20), 2179-2191","doi":"10.1080/15384101.2022.2092166","pmid":"35726575","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Substance P increased pyroptotic cell death and inflammation in bronchial cells, activating the PI3K/AKT/NF-κB pathway.","whyItMatters":"Understanding how Substance P exacerbates asthma could lead to new therapeutic approaches to manage the condition. Targeting the pathways involved may help reduce inflammation and improve patient outcomes.","specificNumbers":"","methodology":"The study used clinical data from asthma patients and pre-clinical experiments with bronchial epithelial cells and asthmatic mice models to analyze the effects of Substance P.","limitations":"The study primarily focuses on in vitro and animal models, which may not fully represent human asthma pathology."},{"rthcId":"RPEP-06303","title":"Ghrelin signaling in dCA1 suppresses neuronal excitability and impairs memory acquisition via PI3K/Akt/GSK-3β cascades.","authors":"Li, Nan; Xiao, Kewei; Mi, Xue; Li, Na; Guo, Li; Wang, Xiaorong; Sun, Yuxiang; Li, Guo-Dong; Zhou, Yu","year":2022,"journal":"Neuropharmacology, 203, 108871","doi":"10.1016/j.neuropharm.2021.108871","pmid":"34742928","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Ghrelin infusion in the CA1 region of the hippocampus impairs memory acquisition.","whyItMatters":"Understanding how ghrelin affects memory could provide insights into metabolic disorders and cognitive decline. This research may lead to new therapeutic strategies for memory-related issues.","specificNumbers":"","methodology":"The study used micro-infusion of ghrelin in the dorsal CA1 region of the hippocampus during training and assessed its effects on memory acquisition and neuronal excitability.","limitations":"The study primarily focuses on animal models, which may not fully translate to human memory processes."},{"rthcId":"RPEP-06304","title":"Functional Molecules of Intestinal Mucosal Products and Peptones in Animal Nutrition and Health.","authors":"Li, Peng; Wu, Guoyao","year":2022,"journal":"Advances in experimental medicine and biology, 1354, 263-277","doi":"10.1007/978-3-030-85686-1_13","pmid":"34807446","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Supplementing diets with up to 5% intestinal mucosal products improves growth and health in livestock and other animals.","whyItMatters":"Enhancing animal nutrition with these products can lead to better health outcomes and more efficient food production. This is particularly relevant for livestock and aquaculture industries.","specificNumbers":"","methodology":"The study reviewed existing evidence on the effects of intestinal mucosal products and peptones in animal nutrition.","limitations":"The study primarily reviews existing literature, which may limit the applicability of findings to specific animal species or conditions."},{"rthcId":"RPEP-06305","title":"SP protects Nile tilapia (Oreochromis niloticus) against acute Streptococcus agalatiae infection.","authors":"Li, Qi; Jiang, Baijian; Zhang, Zhiqiang; Huang, Yongxiong; Xu, Zhou; Chen, Xinjin; Huang, Yu; Jian, Jichang","year":2022,"journal":"Fish & shellfish immunology, 123, 218-228","doi":"10.1016/j.fsi.2022.03.002","pmid":"35257891","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"On-SP improved survival rates during acute bacterial infection in Nile tilapia.","whyItMatters":"Understanding how SP functions in fish can help improve fish health management and disease resistance in aquaculture.","specificNumbers":"","methodology":"The study involved gene identification and analysis of the immune response in Nile tilapia challenged with Streptococcus agalactiae.","limitations":"The study focused on a specific bacterial infection and may not represent other pathogens or environmental conditions."},{"rthcId":"RPEP-06306","title":"N-trimethyl chitosan coated targeting nanoparticles improve the oral bioavailability and antioxidant activity of vitexin.","authors":"Li, Sen; Lv, Hongyan; Chen, Yu; Song, Hongdong; Zhang, Yu; Wang, Shuo; Luo, Lei; Guan, Xiao","year":2022,"journal":"Carbohydrate polymers, 286, 119273","doi":"10.1016/j.carbpol.2022.119273","pmid":"35337500","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The nanoparticles increased the bioavailability and antioxidant activity of vitexin.","whyItMatters":"Improving the bioavailability of vitexin can enhance its health benefits, making it a more effective dietary supplement. This research could lead to better delivery systems for other poorly absorbed compounds.","specificNumbers":"","methodology":"The study involved creating bilayer nanoparticles using soybean peptides and a targeting peptide, followed by ex vivo and in vivo experiments to test their effectiveness.","limitations":"The study primarily focuses on animal models, and results may not directly translate to humans."},{"rthcId":"RPEP-06307","title":"Enzyme-instructed self-assembly (EISA) assists the self-assembly and hydrogelation of hydrophobic peptides.","authors":"Li, Xinxin; Wang, Youzhi; Zhang, Yiming; Yang, Zhimou; Gao, Jie; Shi, Yang","year":2022,"journal":"Journal of materials chemistry. B, 10(17), 3242-3247","doi":"10.1039/d2tb00182a","pmid":"35437539","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Phosphorylated peptide precursors successfully formed hydrogels upon dephosphorylation.","whyItMatters":"This research provides a novel approach to creating hydrogels from hydrophobic peptides, which could have significant implications for biomedical applications.","specificNumbers":"","methodology":"The study involved synthesizing peptide derivatives and testing their solubility and gelation properties in the presence of alkaline phosphatase.","limitations":"The study primarily focuses on in vitro conditions, which may not fully represent in vivo behavior."},{"rthcId":"RPEP-06308","title":"Advances in oral peptide drug nanoparticles for diabetes mellitus treatment.","authors":"Li, Yan; Zhang, Wen; Zhao, Ruichen; Zhang, Xin","year":2022,"journal":"Bioactive materials, 15, 392-408","doi":"10.1016/j.bioactmat.2022.02.025","pmid":"35386357","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Nanoparticles can significantly improve the oral bioavailability of peptide drugs.","whyItMatters":"Improving the oral delivery of peptide drugs could lead to better patient compliance and treatment outcomes for diabetes. This research highlights innovative solutions to a common problem in drug delivery.","specificNumbers":"","methodology":"This is a review study that analyzes existing research on nanoparticles for oral peptide drug delivery.","limitations":"As a review, it does not present new experimental data and relies on existing literature, which may vary in quality."},{"rthcId":"RPEP-06309","title":"A stimulator of interferon gene (CgSTING) involved in antimicrobial immune response of oyster Crassostrea gigas.","authors":"Li, Youjing; Qiao, Xue; Hou, Lilin; Liu, Xiyang; Li, Qing; Jin, YuHao; Li, Yinan; Wang, Lingling; Song, Linsheng","year":2022,"journal":"Fish & shellfish immunology, 128, 82-90","doi":"10.1016/j.fsi.2022.07.059","pmid":"35917891","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CgSTING expression increased 12.91-fold after bacterial stimulation, while its knockdown led to a 26.78-fold increase in bacterial counts.","whyItMatters":"Understanding how oysters defend against bacterial infections can inform aquaculture practices and improve oyster health management. It also sheds light on innate immune mechanisms in marine organisms.","specificNumbers":"","methodology":"The study involved RNA interference to knock down CgSTING and measured subsequent changes in immune-related gene expression and bacterial counts.","limitations":"The study focused on a single species and specific bacterial strain, which may limit the generalizability of the findings."},{"rthcId":"RPEP-06310","title":"Incorporation of Endosomolytic Peptides with Varying Disruption Mechanisms into EGFR-Targeted Protein Conjugates: The Effect on Intracellular Protein Delivery and EGFR Specificity in Breast Cancer Cells.","authors":"Lieser, Rachel M; Li, Qirun; Chen, Wilfred; Sullivan, Millicent O","year":2022,"journal":"Molecular pharmaceutics, 19(2), 661-673","doi":"10.1021/acs.molpharmaceut.1c00788","pmid":"35040326","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"All four endosomolytic peptides (Aurein 1.2, GALA, HA2, and L17E) enhanced endosomal disruption when fused to EGFR-targeted protein conjugates, increasing the half-life of internalized protein and reducing lysosomal degradation. However, only Aurein 1.2 and GALA maintained EGFR-targeting specificity, while HA2 and L17E compromised the ability to selectively target cancer cells. This demonstrates that the choice of endosomal escape peptide significantly affects both targeting capability and bioactivity of the delivery system.","whyItMatters":"Most protein-based drugs can only reach targets on the outside of cells because getting proteins inside cells intact is extremely difficult. This research advances the design of peptide-based delivery systems that could unlock intracellular protein therapies for cancers like EGFR-positive breast cancer, while showing that not all delivery peptides are interchangeable — some sacrifice targeting precision for entry efficiency.","specificNumbers":"","methodology":"Researchers created fusion protein conjugates by attaching four different endosomolytic peptides (Aurein 1.2, GALA, HA2, L17E) to EGFR-targeted proteins. They systematically compared the conjugates in breast cancer cells using the Gal8-YFP assay to measure endosomal escape, along with assays for lysosomal colocalization, protein half-life, EGFR specificity, and cytotoxicity. This was an in vitro (cell culture) study.","limitations":"All experiments were performed in cell culture (in vitro), so results may not directly translate to living organisms where factors like immune response, blood clearance, and tissue penetration come into play. The study tested only four endosomolytic peptides, and performance may vary with different target receptors or cell types beyond EGFR-positive breast cancer cells."},{"rthcId":"RPEP-06311","title":"Acidic and basic self-assembling peptide and peptide-graphene oxide hydrogels: characterisation and effect on encapsulated nucleus pulposus cells.","authors":"Ligorio, Cosimo; Vijayaraghavan, Aravind; Hoyland, Judith A; Saiani, Alberto","year":2022,"journal":"Acta biomaterialia, 143, 145-158","doi":"10.1016/j.actbio.2022.02.022","pmid":"35196554","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Self-assembling peptide hydrogels made from the octapeptide FEFKFEFK (F8) could be formulated at acidic (pH 4) or basic (pH 9) conditions using the same peptide sequence. Acidic hydrogels induced a catabolic (degenerative) response in nucleus pulposus cells — increased expression of MMP-3, ADAMTS-4 degradative enzymes, neurotrophic factors NGF and BDNF, and NF-κB phosphorylation. Graphene oxide-containing acidic hydrogels (GO-F8) showed a milder inflammatory response with the highest expression of desired NP matrix proteins (aggrecan and collagen II). All systems buffered within 30 minutes in cell culture media, and the cellular pH response was transitory, peaking at 3 days and decreasing by 7 days.","whyItMatters":"Intervertebral disc degeneration is a major cause of chronic back pain affecting millions of people. Self-assembling peptide hydrogels offer a versatile biomaterial platform for studying and potentially treating disc disease. This study shows that the pH of the peptide scaffold influences cell behavior — and that adding graphene oxide to the peptide hydrogel reduces inflammation while boosting production of the structural proteins that discs need.","specificNumbers":"Peptide: FEFKFEFK (8 amino acids) · pH 4 (acidic) and pH 9 (basic) formulations · buffered within 30 min · inflammatory peak at 3 days · recovery by 7 days · GO-F8 had highest aggrecan/collagen II expression","methodology":"In vitro study formulating hydrogels from the self-assembling octapeptide FEFKFEFK at acidic and basic pH, with and without graphene oxide. Nucleus pulposus cells were encapsulated and cultured for up to 7 days. Gene expression of degradative enzymes, inflammatory markers, neurotrophic factors, and matrix proteins was measured by qPCR. Morphology and rheological properties were characterized.","limitations":"In vitro cell culture study — results may not translate to in vivo disc conditions. Only one cell type (NP cells) was tested. The transitory nature of pH effects (peaking at 3 days, declining by 7) raises questions about long-term relevance. No animal disc degeneration model was used."},{"rthcId":"RPEP-06312","title":"Rationalisation of Antifungal Properties of α-Helical Pore-Forming Peptide, Mastoparan B.","authors":"Lim, Edward Jianyang; Leng, Eunice Goh Tze; Tram, Nhan Dai Thien; Periayah, Mercy Halleluyah; Ee, Pui Lai Rachel; Barkham, Timothy Mark Sebastian; Poh, Zhi Sheng; Verma, Navin Kumar; Lakshminarayanan, Rajamani","year":2022,"journal":"Molecules (Basel, Switzerland), 27(4)","doi":"10.3390/molecules27041438","pmid":"35209228","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Mastoparan B exhibited potent antifungal activity against Candida species, outperforming cecropin A.","whyItMatters":"With rising antifungal resistance, finding new treatments is crucial. Peptide-based therapies could provide safer alternatives.","specificNumbers":"","methodology":"The study involved testing four antimicrobial peptides against clinically relevant fungal pathogens and assessing their cytocompatibility with human cells.","limitations":"The study primarily focused on in vitro results, which may not fully translate to clinical settings."},{"rthcId":"RPEP-06313","title":"Innovative treatments for epilepsy: Venom peptides, cannabinoids, and neurostimulation.","authors":"Lima, Larissa Silva de; Loyola, Vinícius; Bicca, João Victor Montenegro Luzardo; Faro, Lucas; Vale, Camilla Lepesqueur Costa; Lotufo Denucci, Bruna; Mortari, Márcia Renata","year":2022,"journal":"Journal of neuroscience research, 100(11), 1969-1986","doi":"10.1002/jnr.25114","pmid":"35934922","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Peptides from animal venoms and cannabinoids may provide new treatment avenues for drug-resistant epilepsy.","whyItMatters":"About 30% of epilepsy patients do not respond to standard medications, making alternative treatments crucial. Exploring these options could significantly enhance patient care.","specificNumbers":"","methodology":"This study is a review of current literature on innovative epilepsy treatments.","limitations":"As a review, it summarizes existing research but does not present new experimental data."},{"rthcId":"RPEP-06314","title":"Amyloidogenicity of peptides targeting diabetes and obesity.","authors":"Lima, Luís Maurício T R; Icart, Luis Peña","year":2022,"journal":"Colloids and surfaces. B, Biointerfaces, 209(Pt 1), 112157","doi":"10.1016/j.colsurfb.2021.112157","pmid":"34715595","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review covers aggregation behavior across the major therapeutic peptide families used in metabolic disease:\n\n- Insulin and insulin analogs — the original and most-studied therapeutic peptide, prone to amyloid fibril formation\n- Amylin analogs (pramlintide, davalintide, cagrilintide) — based on a peptide that naturally forms amyloid in the pancreas\n- GLP-1 receptor agonists (liraglutide, exenatide, semaglutide) — newer drugs with their own aggregation profiles\n- Glucagon and related peptides\n\nImproper formulation, storage, manipulation, and usage can lead to high molecular weight products (HMWP) that are either amorphous or amyloid in nature. These aggregates can cause loss of biological activity, short-term immune reactions, and long-term silent inactivation of the drug.","whyItMatters":"With hundreds of millions of people now using peptide drugs for diabetes and obesity, ensuring these medications remain stable and effective is a massive quality challenge. A single vial of insulin that has aggregated may look unchanged but deliver reduced or unpredictable dosing. Understanding why peptide drugs clump — and how to prevent it — is essential for patient safety, drug manufacturing, and the development of next-generation peptide therapeutics with improved stability profiles.","specificNumbers":"","methodology":"This is a narrative review synthesizing published research on the aggregation behavior of therapeutic polypeptides used in diabetes and metabolic diseases. The review covers aggregation mechanisms, analytical detection techniques, physical and chemical stability factors, and strategies for preventing high molecular weight product formation.","limitations":"As a narrative review, the paper provides qualitative synthesis without meta-analysis or quantitative data from specific stability studies. The aggregation behavior of newer peptide drugs (like oral semaglutide and tirzepatide) may not be fully covered. Clinical evidence for immune reactions from aggregated peptide drugs in humans is limited and largely inferred from preclinical and in vitro studies. The review focuses primarily on physicochemical aspects rather than clinical outcomes."},{"rthcId":"RPEP-06315","title":"Animal venoms as a source of antiviral peptides active against arboviruses: a systematic review.","authors":"Lima, William Gustavo; Maia, César Quadros; de Carvalho, Thayane Santos; Leite, Gustavo Oliveira; Brito, Júlio César Moreira; Godói, Isabella Piassi Dias; de Lima, Maria Elena; Ferreira, Jaqueline Maria Siqueira","year":2022,"journal":"Archives of virology, 167(9), 1763-1772","doi":"10.1007/s00705-022-05494-8","pmid":"35723756","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Animal venom-derived peptides showed antiviral activity against multiple arboviruses.","whyItMatters":"With rising arboviral infections, finding new antiviral treatments is crucial. This research highlights a novel source for potential antiviral drugs.","specificNumbers":"","methodology":"The study systematically reviewed in vitro and in vivo research on antiviral peptides from animal venoms.","limitations":"The review is based on existing studies, which may vary in quality and methodology."},{"rthcId":"RPEP-06316","title":"Examining the effect of chronic intranasal oxytocin administration on the neuroanatomy and behavior of three autism-related mouse models.","authors":"Lindenmaier, Zsuzsa; Ellegood, Jacob; Stuive, Monique; Easson, Kaitlyn; Yee, Yohan; Fernandes, Darren; Foster, Jane; Anagnostou, Evdokia; Lerch, Jason P","year":2022,"journal":"NeuroImage, 257, 119243","doi":"10.1016/j.neuroimage.2022.119243","pmid":"35508216","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across three autism-related mouse models (16p11.2 deletion, Shank3 knockout, Fmr1 knockout), chronic intranasal oxytocin (0.6 IU daily for 28 days) did not produce significant changes in neuroanatomy as measured by structural MRI, though some trending effects were observed.\n\nNo significant effect on social behavior was found in any strain. The only significant behavioral finding was normalization of a grooming deficit in the Fmr1 knockout model. No other treatment effects survived multiple comparisons correction. The authors conclude that chronic oxytocin had limited effects, and no promising pattern of treatment susceptibility by genotype emerged.","whyItMatters":"This is an important negative result. Oxytocin has generated enormous public and scientific interest as a potential autism treatment, but this well-designed, multi-model study found very limited benefits. Negative results like these are essential for guiding the field away from ineffective approaches and toward more promising therapies. The finding that different genetic backgrounds didn't show different responses also dampens hopes for genotype-guided oxytocin therapy.","specificNumbers":"","methodology":"Large randomized, blinded, placebo-controlled preclinical study. Three autism mouse models received intranasal oxytocin (0.6 IU) or placebo daily for 28 days starting at 5 weeks of age. Brain structure was assessed with longitudinal in vivo T1-weighted MRI (90 μm resolution) and high-resolution ex vivo T2-weighted MRI (40 μm resolution) using deformation-based morphometry. Behavior was tested across multiple domains including social and repetitive behaviors.","limitations":"Mouse models of autism have inherent limitations in replicating human autism, which is far more heterogeneous. The dose (0.6 IU) and 28-day duration may not capture effects that require different dosing or longer treatment. Intranasal delivery to the mouse brain may not mirror human intranasal delivery. The study examined three specific genetic models, which may not represent all forms of autism."},{"rthcId":"RPEP-06317","title":"Basal insulin intensification with GLP-1RA and dual GIP and GLP-1RA in patients with uncontrolled type 2 diabetes mellitus: A rapid review of randomized controlled trials and meta-analysis.","authors":"Lisco, Giuseppe; De Tullio, Anna; Disoteo, Olga; De Geronimo, Vincenzo; Piazzolla, Giuseppina; De Pergola, Giovanni; Giagulli, Vito Angelo; Jirillo, Emilio; Guastamacchia, Edoardo; Sabbà, Carlo; Triggiani, Vincenzo","year":2022,"journal":"Frontiers in endocrinology, 13, 920541","doi":"10.3389/fendo.2022.920541","pmid":"36157450","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tirzepatide reduced HbA1c by 1% and body weight by 3.95 kg without increasing hypoglycemia risk.","whyItMatters":"This research highlights a new effective treatment option for patients with uncontrolled type 2 diabetes, addressing both glucose control and weight management.","specificNumbers":"","methodology":"The study is a systematic review and meta-analysis of eleven randomized controlled trials.","limitations":"The review is based on existing trials, which may vary in quality and design, potentially affecting the generalizability of the findings."},{"rthcId":"RPEP-06318","title":"Human intestinal bitter taste receptors regulate innate immune responses and metabolic regulators in obesity.","authors":"Liszt, Kathrin I; Wang, Qiaoling; Farhadipour, Mona; Segers, Anneleen; Thijs, Theo; Nys, Linda; Deleus, Ellen; Van der Schueren, Bart; Gerner, Christopher; Neuditschko, Benjamin; Ceulemans, Laurens J; Lannoo, Matthias; Tack, Jan; Depoortere, Inge","year":2022,"journal":"The Journal of clinical investigation, 132(3)","doi":"10.1172/JCI144828","pmid":"34784295","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"TAS2Rs in the gut induce antimicrobial peptide release and regulate immune factors, impacting E. coli growth.","whyItMatters":"Understanding the role of TAS2Rs in gut immunity could lead to new treatments for obesity and related metabolic disorders. This research highlights the potential of genetic markers in predicting responses to therapies.","specificNumbers":"","methodology":"The study involved human jejunal crypts and assessed responses to bitter agonists, including RNA sequencing and proteomics.","limitations":"The study primarily focused on human jejunal crypts and may not fully represent the entire gut environment. Further research is needed to confirm findings in larger, diverse populations."},{"rthcId":"RPEP-06319","title":"Bio-Membrane Internalization Mechanisms of Arginine-Rich Cell-Penetrating Peptides in Various Species.","authors":"Liu, Betty Revon; Chiou, Shiow-Her; Huang, Yue-Wern; Lee, Han-Jung","year":2022,"journal":"Membranes, 12(1)","doi":"10.3390/membranes12010088","pmid":"35054614","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Arginine-rich CPPs utilize direct membrane translocation and endocytosis for cargo delivery.","whyItMatters":"Understanding how CPPs work can enhance their use in drug delivery systems, potentially improving treatments in medicine. Their non-toxic nature and versatility make them valuable tools in biomedicine.","specificNumbers":"","methodology":"The study involved a review of existing literature on the mechanisms of intracellular uptake of arginine-rich CPPs across various species.","limitations":"The study is a review and does not include original experimental data; thus, it may not provide new empirical insights."},{"rthcId":"RPEP-06320","title":"Separation and identification of collagen peptides derived from enzymatic hydrolysate of Salmo salar skin and their anti-inflammatory activity in lipopolysaccharide (LPS)-induced RAW264.7 inflammatory model.","authors":"Liu, Hui; Li, Bo","year":2022,"journal":"Journal of food biochemistry, 46(7), e14122","doi":"10.1111/jfbc.14122","pmid":"35332533","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Peptide QA had an IC50 value of 849.3 μM against NO production.","whyItMatters":"With the risks associated with long-term anti-inflammatory drug use, natural alternatives like these peptides could provide safer options. Utilizing fish byproducts also promotes sustainability in food production.","specificNumbers":"","methodology":"The study used enzymatic hydrolysis, followed by ultrafiltration and chromatography, to identify peptides.","limitations":"The study primarily focused on in vitro models, which may not fully represent effects in humans."},{"rthcId":"RPEP-06321","title":"Various bioactive peptides in collagen hydrolysate from salmo salar skin and the combined inhibitory effects on atherosclerosis in vitro and in vivo.","authors":"Liu, Hui; Yang, Yijie; Liu, Yibo; Cui, Liyuan; Fu, Lulu; Li, Bo","year":2022,"journal":"Food research international (Ottawa, Ont.), 157, 111281","doi":"10.1016/j.foodres.2022.111281","pmid":"35761591","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Collagen hydrolysate from salmon skin inhibited arterial thickening and plaque formation in mice, comparable to aspirin.","whyItMatters":"Understanding how dietary supplements like salmon skin collagen can prevent atherosclerosis may lead to new strategies for heart disease prevention.","specificNumbers":"","methodology":"The study involved in vitro tests for anti-inflammatory and antioxidant activities, followed by in vivo tests on ApoE-/- mice fed high-fat diets.","limitations":"The study was conducted in mice, and results may not directly translate to humans; long-term effects were not assessed."},{"rthcId":"RPEP-06322","title":"Protection effect of thymosin β4 on ethanol injury in corneal stromal keratocyte.","authors":"Liu, Jinghua; Guo, Chen; Hao, Peng; Wang, Peihong; Li, Linghan; Wang, Yuchuan; Li, Xuan","year":2022,"journal":"BMC ophthalmology, 22(1), 33","doi":"10.1186/s12886-022-02255-8","pmid":"35062902","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Thymosin beta-4 alleviated ethanol-induced oxidative stress and apoptosis in human corneal keratocytes by upregulating protective factors (Bcl-2, catalase, CuZnSOD) and inhibiting the cell death marker Caspase-3. Tβ4 also promoted cell proliferation through upregulated Ki67 expression and accelerated corneal wound healing in both in vitro and in vivo models. In mouse corneas treated with ethanol, Tβ4 promoted reconstruction of the damaged corneal stroma, confirmed by fluorescein sodium staining and histological examination.","whyItMatters":"Corneal damage from ethanol exposure during eye surgery is a real clinical problem. This research suggests thymosin beta-4 could be developed as a protective eye drop or treatment to reduce corneal damage and speed recovery after procedures that involve alcohol contact with the cornea.","specificNumbers":"","methodology":"Researchers used human corneal keratocytes (HCKs) and BALB/c mice to create ethanol injury models both in vitro and in vivo. Cell metabolic activity was measured with CCK-8 assay. Reactive oxygen species were detected using DCFH-DA. Apoptosis was assessed by TUNEL staining. Cell proliferation and migration were measured with wound healing insert assays. In mice, corneal healing was tracked with fluorescein staining and H&E histology. Gene and protein expression were analyzed by RT-qPCR, ELISA, and immunostaining.","limitations":"The study used cell culture and mouse models, which may not fully replicate human corneal healing. Specific dosing, treatment timing, and concentration-response relationships were not detailed in the abstract. Long-term safety and efficacy of Tβ4 for corneal applications were not assessed. The mouse cornea differs from the human cornea in size and structure."},{"rthcId":"RPEP-06323","title":"Association between different GLP-1 receptor agonists and gastrointestinal adverse reactions: A real-world disproportionality study based on FDA adverse event reporting system database.","authors":"Liu, Lulu; Chen, Jia; Wang, Lei; Chen, Chen; Chen, Li","year":2022,"journal":"Frontiers in endocrinology, 13, 1043789","doi":"10.3389/fendo.2022.1043789","pmid":"36568085","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RAs were linked to gastrointestinal disorders (ROR, 1.46; 95% CI, 1.44-1.49), with semaglutide showing the highest risks for nausea (ROR, 7.41) and pancreatitis (ROR, 32.67).","whyItMatters":"Understanding the gastrointestinal side effects of GLP-1 RAs can help healthcare providers make better treatment decisions. This knowledge is crucial for patient safety and effective diabetes management.","specificNumbers":"","methodology":"The study used disproportionality analysis on data from the FDA Adverse Event Reporting System (FAERS) from January 2018 to September 2022.","limitations":"The study relies on reported adverse events, which may not capture all cases or accurately reflect the incidence rates."},{"rthcId":"RPEP-06324","title":"Exploring ex vivo peptideolysis of thymopentin and lipid-based nanocarriers towards oral formulations.","authors":"Liu, Mengyang; Svirskis, Darren; Proft, Thomas; Loh, Jacelyn; Chen, Shuo; Kang, Dali; Wen, Jingyuan","year":2022,"journal":"International journal of pharmaceutics, 625, 122123","doi":"10.1016/j.ijpharm.2022.122123","pmid":"35995317","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"TP5 degradation followed pseudo-first-order kinetics and was primarily driven by luminal enzymes throughout the intestinal tract (duodenum, jejunum, ileum, and colon). Three enzyme inhibitors significantly reduced TP5 breakdown:\n\n- Soybean trypsin and chymotrypsin inhibitors (SBTCI) — considerable decrease in peptidolysis\n- Bestatin — significant reduction\n- EDTA — significant reduction\n\nThree lipid-based nanocarrier systems (microemulsions, niosomes, and solid lipid nanoparticles) loaded with TP5 and SBTCI provided superior protection against degradation by both luminal contents and mucosal homogenates for 6 hours, compared to the unprotected peptide in solution.","whyItMatters":"Most peptide drugs must be injected because the digestive system destroys them before they can be absorbed. This is a major barrier to patient compliance and quality of life. Thymopentin is an immunomodulatory peptide used to treat immune deficiencies, autoimmune conditions, and as an adjunct in cancer therapy. Developing an oral form could make it accessible to far more patients and improve adherence, while the approach itself could be applied to other therapeutic peptides facing the same delivery challenge.","specificNumbers":"","methodology":"Researchers extracted mucosal and luminal components from four sections of rat intestine (duodenum, jejunum, ileum, colon) and measured TP5 degradation kinetics with and without these components. Three enzyme inhibitors (EDTA, SBTCI, bestatin) were screened for their ability to block TP5 breakdown. TP5 with the best inhibitor (SBTCI) was then loaded into three lipid-based nanocarrier systems. These were characterized for morphology, particle size, zeta potential, and entrapment efficiency, then tested for TP5 protection in ex vivo intestinal degradation studies.","limitations":"All experiments were conducted ex vivo using rat intestinal tissues, which may not perfectly replicate human gastrointestinal conditions. No in vivo oral absorption or bioavailability data were generated. The entrapment efficiency and long-term stability of the nanocarrier formulations are not discussed in detail. The transition from ex vivo protection to actual systemic absorption in a living organism involves additional barriers (mucus layer, epithelial transport) not addressed here."},{"rthcId":"RPEP-06325","title":"A Potential MDM2 Inhibitor Formed by Restoring the Native Conformation of the p53 α-Helical Peptide on Gold Nanoparticles.","authors":"Liu, Qi; Sheng, Lingjie; Liu, Yuan-Yuan; Gao, Tiange; Wang, Haifang; Liu, Yuanfang; Cao, Aoneng","year":2022,"journal":"ChemMedChem, 17(5), e202100623","doi":"10.1002/cmdc.202100623","pmid":"35037401","tags":["p53-mdm2","nanoparticle-peptides"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Researchers attached a peptide from the p53 tumor suppressor protein onto gold nanoparticles and were able to restore its natural helical shape — a shape it loses when floating freely in solution. This 'Goldbody' construct specifically bound to MDM2, the protein that normally disables p53 in cancer cells. Surface plasmon resonance confirmed strong, specific binding between the Goldbody and MDM2, demonstrating its potential as an MDM2 inhibitor that could reactivate the body's tumor suppression machinery.","whyItMatters":"In about half of all human cancers, the tumor suppressor p53 is intact but silenced by MDM2. If you can block the MDM2-p53 interaction, you can reactivate p53 and trigger cancer cell death. This study introduces a novel approach — using gold nanoparticles to force a peptide into the exact shape needed to block MDM2 — which could overcome the stability problems that have plagued previous peptide-based MDM2 inhibitors.","specificNumbers":"","methodology":"The team used a conformational engineering technique to attach a p53 transactivation domain (TAD) peptide to gold nanoparticles (AuNPs). They verified that the peptide adopted its correct alpha-helical structure using circular dichroism spectroscopy, then tested binding to MDM2 protein using surface plasmon resonance (SPR) experiments.","limitations":"This is an early-stage proof-of-concept study with no cell-based or animal data. The Goldbody's ability to actually inhibit MDM2 function inside living cells, its cellular uptake, toxicity profile, and in vivo behavior are all unknown. Gold nanoparticle delivery to tumors presents its own challenges."},{"rthcId":"RPEP-06326","title":"Evaluating the Properties of Ginger Protease-Degraded Collagen Hydrolysate and Identifying the Cleavage Site of Ginger Protease by Using an Integrated Strategy and LC-MS Technology.","authors":"Liu, Wei; Yang, Wenning; Li, Xueyan; Qi, Dongying; Chen, Hongjiao; Liu, Huining; Yu, Shuang; Wang, Guopeng; Liu, Yang","year":2022,"journal":"Molecules (Basel, Switzerland), 27(15)","doi":"10.3390/molecules27155001","pmid":"35956951","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The ginger protease-degraded collagen hydrolysate showed a degree of hydrolysis of 20.37% and DPPH scavenging activity of 77.73%.","whyItMatters":"Understanding how ginger protease interacts with collagen can lead to better applications in health and nutrition. The findings may support the development of functional foods or supplements.","specificNumbers":"","methodology":"The study used both in vitro and in vivo methods, including measuring hydrolysis degree and antioxidant activity, as well as absorption studies in rats.","limitations":"The study primarily focused on animal models, which may not fully represent human absorption and effects."},{"rthcId":"RPEP-06327","title":"Molecular characterization of fish cytokine IL-17C from Amphiprion clarkii and its immunomodulatory effects on the responses to pathogen-associated molecular patterns and bacterial challenges.","authors":"Liyanage, D S; Omeka, W K M; Yang, Hyerim; Lim, Chaehyeon; Choi, Cheol Young; Lee, Jehee","year":2022,"journal":"Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology, 257, 110669","doi":"10.1016/j.cbpb.2021.110669","pmid":"34428552","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"IL-17C increased survival rates of fish cells infected with E. coli, showing a concentration-dependent effect.","whyItMatters":"Understanding IL-17C's role in fish immunity could inform aquaculture practices and enhance disease resistance in fish populations.","specificNumbers":"","methodology":"The study involved gene characterization, transcription analysis, and bacterial assays using fish cells.","limitations":"The study primarily focuses on a single fish species, which may limit the generalizability of the findings."},{"rthcId":"RPEP-06328","title":"Tumor pH-functionalized and charge-tunable nanoparticles for the nucleus/cytoplasm-directed delivery of oxaliplatin and miRNA in the treatment of head and neck cancer.","authors":"Lo, Yu-Li; Lin, Hua-Ching; Tseng, Wei-Hsuan","year":2022,"journal":"Acta biomaterialia, 153, 465-480","doi":"10.1016/j.actbio.2022.09.027","pmid":"36115656","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The peptide-modified nanoparticles successfully delivered oxaliplatin to the cell nucleus and miR-320 to the cytoplasm in human tongue squamous carcinoma cells. The pH-responsive coating protected the peptides during blood circulation and exposed them at acidic tumor sites for active targeting.\n\nThis is the first study to demonstrate concurrent modulation of six major cancer signaling pathways (NRP1/Rac1, PI3K/Akt/mTOR, GSK-3β/FOXM1/β-catenin, P-gp/MRPs, KRAS/Erk/Oct4/Yap1, and N-cadherin/Vimentin/Slug), simultaneously inhibiting cancer growth, progression, and multidrug resistance. In mice bearing SAS tumors, the combination nanoparticles showed superior antitumor efficacy and remarkably decreased oxaliplatin-associated toxicities.","whyItMatters":"Head and neck cancer often develops resistance to chemotherapy, and the side effects of drugs like oxaliplatin limit how much can be given. These nanoparticles address both problems: they concentrate the drug at the tumor site (reducing toxicity elsewhere) and combine it with a gene therapy molecule that attacks drug resistance pathways. The ability to deliver different therapeutics to different compartments within the same cell represents a sophisticated advance in cancer nanomedicine.","specificNumbers":"","methodology":"The researchers designed nanoparticles incorporating oxaliplatin and miR-320, modified with a targeting ligand, cell-penetrating peptide, and nucleus-targeted peptide. A charge/size-tunable polyglutamic acid-PEG shield protected the peptides during circulation and dissolved at acidic tumor pH. Drug encapsulation, pH-responsive release, cellular uptake, intracellular localization, and signaling pathway effects were tested in human tongue cancer SAS cells. Antitumor efficacy and toxicity were evaluated in SAS tumor-bearing mice.","limitations":"The study used cell lines and mouse xenograft models, which may not fully represent human head and neck cancer biology. The complexity of the nanoparticle design (multiple peptides, coating, dual payloads) may present manufacturing and scalability challenges. Long-term toxicity and immune responses to the nanoparticles were not assessed. The xenograft model lacks a functioning immune system, which plays a major role in human cancer treatment outcomes."},{"rthcId":"RPEP-06329","title":"Crotalphine Modulates Microglia M1/M2 Phenotypes and Induces Spinal Analgesia Mediated by Opioid-Cannabinoid Systems.","authors":"Lopes, Flavia S R; Giardini, Aline C; Sant'Anna, Morena B; Kimura, Louise F; Bufalo, Michelle C; Vigerelli, Hugo; Zambelli, Vanessa O; Picolo, Gisele","year":2022,"journal":"International journal of molecular sciences, 23(19)","doi":"10.3390/ijms231911571","pmid":"36232883","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Crotalphine (100 µg/kg, oral) produced analgesia lasting up to 24 hours in a chronic neuropathic pain model (partial sciatic nerve ligation, 14 days post-surgery). The analgesic effect was mediated by both opioid receptors (mu, kappa, and delta — blocked by CTOP, nor-BNI, and naltrindole respectively) and cannabinoid receptors (CB1 and CB2 — blocked by AM251 and AM630).\n\nCrotalphine also decreased spinal cord IL-6 release and shifted microglia from a pro-inflammatory M1 phenotype to an anti-inflammatory M2 phenotype, as demonstrated by reduced CD86 and increased CD206 expression in BV-2 cells in vitro.","whyItMatters":"Chronic pain affects hundreds of millions worldwide, and current treatments like opioid drugs carry serious side effects and addiction risks. Crotalphine's ability to engage multiple natural pain-relief systems simultaneously — opioid, cannabinoid, and anti-inflammatory — while being effective orally and lasting 24 hours makes it an intriguing candidate for safer pain management.","specificNumbers":"","methodology":"The study used a partial sciatic nerve ligation (PSNL) model in animals to induce chronic neuropathic pain. Crotalphine was given orally, and its analgesic mechanisms were dissected using intrathecal administration of specific receptor antagonists and antibodies against endogenous opioid peptides. Microglial polarization was assessed in vitro using BV-2 cells stimulated with LPS.","limitations":"This study was conducted entirely in animal models and cell cultures, so findings may not directly translate to humans. The specific mechanisms of crotalphine's central activity need further investigation, and long-term safety, tolerance development, and pharmacokinetics have not been assessed."},{"rthcId":"RPEP-06330","title":"Vasoactive Intestinal Peptide Tumor as the Cause of Persistent Diarrhea: A Diagnostic Challenge.","authors":"Lopes, Sara; Alves, Marta; Rodrigues, Pedro","year":2022,"journal":"Cureus, 14(9), e29130","doi":"10.7759/cureus.29130","pmid":"36258959","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The patient had a vasoactive intestinal peptide level greater than 100 pmol/L, confirming VIPoma.","whyItMatters":"This case highlights the importance of recognizing rare tumors in patients with chronic diarrhea, which can lead to serious health issues if misdiagnosed. It underscores the need for awareness among clinicians regarding such conditions.","specificNumbers":"","methodology":"The study involved a case report detailing the patient's clinical presentation, diagnostic imaging, and treatment response.","limitations":"The study is based on a single case, which limits the generalizability of the findings."},{"rthcId":"RPEP-06331","title":"Personality traits and efficacy of anti-CGRP monoclonal antibodies in migraine prevention.","authors":"Lovati, Carlo; Bernasconi, Gianna; Capogrosso, Chiara; Molteni, Laura; Giorgetti, Federica; Dell'Osso, Bernardo; Pantoni, Leonardo","year":2022,"journal":"Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 43(9), 5765-5767","doi":"10.1007/s10072-022-06251-0","pmid":"35842569","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 97 patients treated with CGRP monoclonal antibodies (33 galcanezumab, 13 fremanezumab, 51 erenumab), response rates for monthly headache day reduction were: 54.6% full responders (>50% reduction), 13.4% partial responders (30-50%), and 32% non-responders (<30%).\n\nPID-5 personality assessment revealed that non-responders had significantly higher scores in disinhibition, particularly in anhedonia and depressivity facets. For painkiller use reduction, non-responders showed increased depressivity and distractibility. For disability (MIDAS) improvement, non-responders scored higher in antagonism and submissiveness. The pattern suggests that traits associated with depressed mood and difficulty experiencing pleasure predict poorer treatment response.","whyItMatters":"Anti-CGRP therapies are expensive (often $600+/month) and the 32% non-response rate represents a significant clinical and economic burden. If personality traits can help predict who will and won't respond, clinicians could make better prescribing decisions, set realistic patient expectations, and potentially combine CGRP therapy with psychological interventions for patients with higher-risk personality profiles.","specificNumbers":"","methodology":"Observational study of 97 patients treated with anti-CGRP monoclonal antibodies. Three response parameters were measured: monthly headache days (MHD), monthly painkiller intake (MPI), and MIDAS disability score. Patients were classified as full (>50% reduction), partial (30-50%), or non-responders (<30%). All patients completed the Personality Inventory for DSM-5 (PID-5). Personality trait differences between response groups were compared.","limitations":"Small sample size (97 patients) limits statistical power and generalizability. The study is observational with no control group. Personality traits may correlate with other variables (medication overuse, comorbid depression, chronicity) that independently affect treatment response. The short communication format limits methodological detail. The PID-5 assesses personality pathology and may not capture more nuanced trait variations."},{"rthcId":"RPEP-06332","title":"Nanofibrous hemostatic materials: Structural design, fabrication methods, and hemostatic mechanisms.","authors":"Lu, Xuyan; Li, Xiaoran; Yu, Jianyong; Ding, Bin","year":2022,"journal":"Acta biomaterialia, 154, 49-62","doi":"10.1016/j.actbio.2022.10.028","pmid":"36265792","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Nanofibrous materials can be engineered for improved hemostatic function using various methods.","whyItMatters":"Improving hemostatic materials can significantly enhance medical treatment for bleeding, which is critical in emergency care and surgeries.","specificNumbers":"","methodology":"The study is a comprehensive review of existing literature on nanofibrous hemostatic materials, focusing on design, fabrication, and mechanisms.","limitations":"As a review, it summarizes existing research but does not present new experimental data or clinical trials."},{"rthcId":"RPEP-06333","title":"Barriers to the Intestinal Absorption of Four Insulin-Loaded Arginine-Rich Nanoparticles in Human and Rat.","authors":"Lundquist, Patrik; Khodus, Georgiy; Niu, Zhigao; Thwala, Lungile Nomcebo; McCartney, Fiona; Simoff, Ivailo; Andersson, Ellen; Beloqui, Ana; Mabondzo, Aloise; Robla, Sandra; Webb, Dominic-Luc; Hellström, Per M; Keita, Åsa V; Sima, Eduardo; Csaba, Noemi; Sundbom, Magnus; Preat, Veronique; Brayden, David J; Alonso, Maria Jose; Artursson, Per","year":2022,"journal":"ACS nano, 16(9), 14210-14229","doi":"10.1021/acsnano.2c04330","pmid":"35998570","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The ENCP nanoparticle achieved a 28 ± 9% uptake in the intestinal epithelium.","whyItMatters":"Improving the absorption of peptide drugs like insulin could enhance their effectiveness when taken orally, making treatments more convenient for patients.","specificNumbers":"","methodology":"The study used freshly isolated human jejunal tissue and in situ studies in rat jejunal loops to assess nanoparticle absorption.","limitations":"The study was conducted in vitro and in animal models, which may not fully represent human responses."},{"rthcId":"RPEP-06334","title":"Ameliorative effect of the probiotic peptide against benzo(α)pyrene-induced inflammatory damages in enterocytes.","authors":"Luo, Min; Luo, Dan; Liu, Jie; Wang, Huailing; Liu, Xiaoyu; Yang, Min; Tian, Fangfang; Qin, Suofu; Li, Yuying","year":2022,"journal":"International immunopharmacology, 112, 109255","doi":"10.1016/j.intimp.2022.109255","pmid":"36152539","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"LRCP-1 significantly inhibited BaP-induced cytokine over-release and ROS production.","whyItMatters":"Understanding how probiotics can protect gut health is crucial for developing new treatments for gastrointestinal injuries. This research could lead to new dietary strategies or supplements for better gut health.","specificNumbers":"","methodology":"The study used a bio-assay guided technique to identify peptides in Caco-2 cell cultures and a mouse colitis model.","limitations":"The study primarily used cell cultures and a mouse model, which may not fully replicate human responses."},{"rthcId":"RPEP-06335","title":"A Rapid Self-Assembly Peptide Hydrogel for Recruitment and Activation of Immune Cells.","authors":"Luo, Ruyue; Wan, Yuan; Luo, Xinyi; Liu, Guicen; Li, Zhaoxu; Chen, Jialei; Su, Di; Lu, Na; Luo, Zhongli","year":2022,"journal":"Molecules (Basel, Switzerland), 27(2)","doi":"10.3390/molecules27020419","pmid":"35056735","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"DRF3 effectively recruited dendritic cells and inhibited renal cell carcinoma growth.","whyItMatters":"This research highlights the potential of peptide hydrogels in immunotherapy and cancer treatment, offering a new approach to enhance immune responses.","specificNumbers":"","methodology":"The study involved characterizing the peptide hydrogel DRF3, assessing its biocompatibility, antigen release, immune cell recruitment, and anti-tumor properties using various microscopy techniques.","limitations":"The study was conducted in vitro, and further research is needed to confirm these effects in vivo."},{"rthcId":"RPEP-06336","title":"A pilot trial of vaccination with Carcinoembryonic antigen and Her2/neu peptides in advanced colorectal cancer.","authors":"Lynch, Kevin T; Squeo, Gabriella C; Kane, William J; Meneveau, Max O; Petroni, Gina; Olson, Walter C; Chianese-Bullock, Kimberly A; Slingluff, Craig L; Foley, Eugene F; Friel, Charles M","year":2022,"journal":"International journal of cancer, 150(1), 164-173","doi":"10.1002/ijc.33793","pmid":"34480368","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Eleven participants with Stage IIIC-IV colorectal cancer received weekly vaccinations with CEA and Her2/neu peptides combined with tetanus helper peptide and GM-CSF in Montanide ISA-51 adjuvant.\n\nSafety: All participants experienced adverse events, with 82% being Grade 1-2 (mild to moderate) — most commonly fatigue and injection site reactions. Two participants (18%) had treatment-related dose-limiting Grade 3 events, both self-limiting.\n\nImmunogenicity: Immune responses (T-cell responses to Her2 or CEA peptides) were detected in 70% of the 10 evaluable participants via interferon-gamma ELISpot assay.\n\nSurvival: Median overall survival was 16 months for the full cohort. Remarkably, among three patients enrolled with no evidence of disease, median overall survival was not reached after more than 10 years of follow-up.","whyItMatters":"Checkpoint blockade immunotherapy works for only a small subset of colorectal cancers (those with microsatellite instability). The vast majority of CRC patients lack effective immunotherapy options. Peptide vaccines that can train the immune system to recognize specific cancer proteins could fill this gap, especially if combined with checkpoint inhibitors. The striking long-term survival in the three disease-free patients is particularly noteworthy and warrants further investigation.","specificNumbers":"","methodology":"This was a pilot clinical trial (NCT00091286) enrolling HLA-A2+ or HLA-A3+ patients with Stage IIIC-IV colorectal cancer. Participants received weekly subcutaneous vaccinations for 3 weeks with CEA and Her2/neu peptides, tetanus helper peptide, and GM-CSF emulsified in Montanide ISA-51 adjuvant. Adverse events were recorded per NCI CTCAE v3. Immunogenicity was assessed by interferon-gamma ELISpot assay on in vitro sensitized peripheral blood mononuclear cells and sentinel immunized node lymphocytes. Survival was tracked with long-term follow-up.","limitations":"This is a very small pilot trial (11 patients, 10 evaluable) without a control group, making it impossible to attribute survival outcomes to the vaccine. The 10-year survival in three patients is intriguing but could reflect favorable disease biology rather than vaccine effect. One participant was retrospectively found ineligible. The study was designed to assess safety and immunogenicity, not efficacy. HLA restriction (A2+ or A3+) limits the eligible patient population. The vaccine did not demonstrate tumor responses in patients with measurable disease."},{"rthcId":"RPEP-06337","title":"Exploring the impact of the recombinant Escherichia coli strain on defensins antimicrobial activity: BL21 versus Origami strain.","authors":"López-Cano, Adrià; Martínez-Miguel, Marc; Guasch, Judith; Ratera, Imma; Arís, Anna; Garcia-Fruitós, Elena","year":2022,"journal":"Microbial cell factories, 21(1), 77","doi":"10.1186/s12934-022-01803-7","pmid":"35527241","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The E. coli BL21 strain produced higher yields and better quality defensins than the Origami B strain.","whyItMatters":"With antibiotic resistance on the rise, finding effective alternatives like antimicrobial peptides is crucial. Understanding how production methods affect these peptides can enhance their therapeutic potential.","specificNumbers":"","methodology":"The study involved producing human α-defensin 5 and bovine lingual antimicrobial peptide in two E. coli strains and comparing their yields and bactericidal activities.","limitations":"The study focused only on two specific E. coli strains and two types of defensins, which may limit the generalizability of the findings."},{"rthcId":"RPEP-06338","title":"The beneficial effects of genetically engineered Escherichia coli Nissle 1917 in obese C57BL/6J mice.","authors":"Ma, Jie; Wang, Junrui; Xu, Lu; Liu, Yuanqi; Gu, Jianwen","year":2022,"journal":"International journal of obesity (2005), 46(5), 1002-1008","doi":"10.1038/s41366-022-01073-8","pmid":"35079130","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"EcN-GM reduced body weight gain and food intake, and improved metabolic markers in obese mice after 8 weeks.","whyItMatters":"This research suggests that genetically modified probiotics could offer a new strategy for managing obesity, a growing health concern worldwide.","specificNumbers":"","methodology":"Obese C57BL/6J mice were divided into three groups and treated with either control E. coli, genetically modified E. coli, or orlistat for 8 weeks, with various health metrics measured.","limitations":"The study was conducted in mice, so results may not directly translate to humans. The long-term effects and safety of EcN-GM were not assessed."},{"rthcId":"RPEP-06339","title":"Diagnosis and management of gastroenteropancreatic neuroendocrine neoplasms by nuclear medicine: Update and future perspective.","authors":"Ma, Xing; Ding, Ying; Li, Wenliang; Li, Qiang; Yang, Hui","year":2022,"journal":"Frontiers in oncology, 12, 1061065","doi":"10.3389/fonc.2022.1061065","pmid":"36483036","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Nuclear medicine techniques can better identify GEP-NENs compared to traditional imaging.","whyItMatters":"Improving the diagnosis and treatment of GEP-NENs can lead to better patient outcomes. As these tumors are often diagnosed late, effective imaging and targeted therapies are crucial.","specificNumbers":"","methodology":"The study is a review of existing literature on nuclear medicine imaging modalities for GEP-NENs.","limitations":"The study is a review and does not present new experimental data or clinical trials."},{"rthcId":"RPEP-06340","title":"Identification of antimicrobial peptides from the human gut microbiome using deep learning.","authors":"Ma, Yue; Guo, Zhengyan; Xia, Binbin; Zhang, Yuwei; Liu, Xiaolin; Yu, Ying; Tang, Na; Tong, Xiaomei; Wang, Min; Ye, Xin; Feng, Jie; Chen, Yihua; Wang, Jun","year":2022,"journal":"Nature biotechnology, 40(6), 921-931","doi":"10.1038/s41587-022-01226-0","pmid":"35241840","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06341","title":"Membrane Molecular Interactions and Induced Structures of CPPs.","authors":"Madani, Fatemeh; Gräslund, Astrid","year":2022,"journal":"Methods in molecular biology (Clifton, N.J.), 2383, 153-165","doi":"10.1007/978-1-0716-1752-6_10","pmid":"34766288","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CPPs utilize both energy-independent and energy-dependent mechanisms for cellular uptake.","whyItMatters":"Understanding CPP interactions with cell membranes can lead to improved drug delivery systems, potentially enhancing treatment efficacy for various diseases.","specificNumbers":"","methodology":"The study reviews biophysical methods like fluorescence spectroscopy and NMR to analyze CPP-membrane interactions.","limitations":"The study primarily focuses on biophysical methods and may not encompass all biological complexities involved in CPP interactions."},{"rthcId":"RPEP-06342","title":"C-peptide determination in the diagnosis of type of diabetes and its management: A clinical perspective.","authors":"Maddaloni, Ernesto; Bolli, Geremia B; Frier, Brian M; Little, Randie R; Leslie, Richard D; Pozzilli, Paolo; Buzzetti, Raffaela","year":2022,"journal":"Diabetes, obesity & metabolism, 24(10), 1912-1926","doi":"10.1111/dom.14785","pmid":"35676794","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06343","title":"Systemic and brain delivery of antidiabetic peptides through nasal administration using cell-penetrating peptides.","authors":"Maeng, Jeehye; Lee, Kyunglim","year":2022,"journal":"Frontiers in pharmacology, 13, 1068495","doi":"10.3389/fphar.2022.1068495","pmid":"36452220","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CPPs can effectively deliver antidiabetic peptides like insulin and exendin-4 through the nasal route.","whyItMatters":"This research could lead to more effective treatments for diabetes and Alzheimer's disease by improving drug delivery methods. It highlights a non-invasive approach that could enhance patient compliance.","specificNumbers":"","methodology":"The review discusses various methodologies for enhancing the nasal delivery of macromolecular therapeutics, focusing on CPPs.","limitations":"As a review, it does not present original experimental data and may not cover all recent advancements in the field."},{"rthcId":"RPEP-06344","title":"Therapeutic Potential of Semaglutide, a Newer GLP-1 Receptor Agonist, in Abating Obesity, Non-Alcoholic Steatohepatitis and Neurodegenerative diseases: A Narrative Review.","authors":"Mahapatra, Manoj K; Karuppasamy, Muthukumar; Sahoo, Biswa M","year":2022,"journal":"Pharmaceutical research, 39(6), 1233-1248","doi":"10.1007/s11095-022-03302-1","pmid":"35650449","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide significantly reduces weight and shows hepatoprotective and neuroprotective effects.","whyItMatters":"Understanding semaglutide's broader therapeutic potential could lead to new treatments for obesity and neurodegenerative diseases. Its approval for obesity management highlights its clinical relevance.","specificNumbers":"","methodology":"The study is a narrative review summarizing findings from various clinical and pre-clinical trials.","limitations":"The review is based on existing studies and does not present new experimental data."},{"rthcId":"RPEP-06345","title":"Plaque-targeted, proteolysis-resistant, activatable and MRI-visible nano-GLP-1 receptor agonist targets smooth muscle cell differentiation in atherosclerosis.","authors":"Maiseyeu, Andrei; Di, Lin; Ravodina, Anastasia; Barajas-Espinosa, Alma; Sakamoto, Atsushi; Chaplin, Alice; Zhong, Jixin; Gao, Huiyun; Mignery, Matthew; Narula, Navneet; Finn, Aloke V; Rajagopalan, Sanjay","year":2022,"journal":"Theranostics, 12(6), 2741-2757","doi":"10.7150/thno.66456","pmid":"35401813","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The treatment reduced plaque burden and cholesterol levels at a low dose of 1 µg/kg.","whyItMatters":"This research highlights a novel way to target atherosclerosis directly, potentially improving treatment options for cardiovascular diseases.","specificNumbers":"","methodology":"The study involved engineering nanoparticles carrying a GLP-1 receptor agonist and testing their effects in Apoe-/- mice through intravenous administration.","limitations":"The study was conducted in mice, and results may not directly translate to humans."},{"rthcId":"RPEP-06346","title":"Role of aspirin activated nitric oxide synthase in controlling DOCA-salt-induced hypertension in rats through the stimulation of renal r-cortexin in kidney cortex cells.","authors":"Maji, Uttam Kumar; Ghosh, Tamal Kanti; Chatterjee, Mitali; Bhattacharya, Suman; Bank, Sarbashri; Jana, Pradipta","year":2022,"journal":"International journal of health sciences, 16(4), 46-57","doi":null,"pmid":"35949696","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06347","title":"Rapid label-free cell-based Approach Membrane Permeability Assay using MALDI-hydrogen-deuterium exchange mass spectrometry for peptides.","authors":"Makarov, Alexey A; Jiang, Yuan; Sondey, Christopher; Zhang, Minjia; Mansueto, My Sam; Pirrone, Gregory F; Huang, Chunhui; Biswas, Kaustav; Duggal, Ruchia; Al-Sayah, Mohammad Ahmed; Regalado, Erik L; Mangion, Ian","year":2022,"journal":"Analytica chimica acta, 1225, 340234","doi":"10.1016/j.aca.2022.340234","pmid":"36038238","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The Cell-based Approach Membrane Permeability Assay (CAMPA) successfully ranked the cell membrane permeability of 24 diverse peptides — including cell-penetrating peptides, stapled peptides, and macrocyclic peptides — using live THP-1 and AsPc-1 cells.\n\nThe method works by briefly exposing peptide-cell mixtures to deuterium oxide. Peptides outside cells undergo hydrogen-deuterium exchange and gain mass, while peptides inside cells are shielded from labeling. MALDI mass spectrometry detects the ratio of labeled to unlabeled peptides over time. Results correlated with previously published permeability data. The assay also distinguished between passive diffusion and active (endocytosis-mediated) transport when an endocytosis inhibitor was added.","whyItMatters":"Peptide drugs are increasingly being developed to hit intracellular targets like transcription factors and protein-protein interactions, but most peptides struggle to cross cell membranes. Having a fast, reliable way to measure cell permeability early in drug development can help scientists prioritize the most promising candidates and avoid wasting resources on peptides that cannot reach their targets inside cells.","specificNumbers":"","methodology":"Peptides were incubated with live THP-1 (human monocytic) and AsPc-1 (pancreatic cancer) cells. At set time points, samples were briefly exposed to deuterium oxide to label extracellular peptides via hydrogen-deuterium exchange. Intracellular peptides were protected from labeling. MALDI mass spectrometry measured the ratio of deuterium-labeled (extracellular) to unlabeled (intracellular) peptides. The entire workflow was automated, including data processing via custom Python scripts. To differentiate passive from active transport, selected experiments included endocytosis inhibitors.","limitations":"The assay was tested with only 24 peptides across two cell lines, which may not capture the full diversity of peptide chemistries or cell types relevant to drug development. The method relies on short deuterium exposure times that may not perfectly quantify permeability for very fast or very slow-permeating peptides. MALDI-MS requires specialized equipment not available in all labs. The approach measures total cell entry but does not reveal where inside the cell peptides accumulate (e.g., cytoplasm vs. endosomes)."},{"rthcId":"RPEP-06348","title":"Regulation of macrophage-associated inflammatory responses by species-specific lactoferricin peptides.","authors":"Malone, Alicia; Clark, Rikki F; Hoskin, David W; Power Coombs, Melanie R","year":2022,"journal":"Frontiers in bioscience (Landmark edition), 27(2), 43","doi":"10.31083/j.fbl2702043","pmid":"35226986","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Bovine lactoferricin downregulated TNF-α and IL-6 in human and mouse macrophages.","whyItMatters":"Understanding how specific peptides regulate inflammation can lead to new treatments for chronic inflammatory diseases. Bovine lactoferricin's unique properties may provide a novel approach to immunotherapy.","specificNumbers":"","methodology":"The study compared the effects of lactoferricin peptides from three species on macrophage inflammatory responses using in vitro assays.","limitations":"The study was conducted in vitro, and the in vivo effects of lactoferricin need further investigation."},{"rthcId":"RPEP-06349","title":"In-silico Screening of Phytoconstituents on Wound Healing Targets - Approaches and Current Status.","authors":"Mandale, Vijaya; Thomas, Asha; Wavhale, Ravindra; Chitlange, Sohan","year":2022,"journal":"Current drug discovery technologies, 19(3), e301121198426","doi":"10.2174/1570163819666211130141442","pmid":"34847843","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Phytoconstituents from herbs can target multiple wound healing processes, including inflammation and angiogenesis.","whyItMatters":"Understanding how natural products can facilitate wound healing could lead to more effective treatments, especially for chronic wounds. This approach may also promote the use of herbal medicine in clinical settings.","specificNumbers":"","methodology":"The study is a systematic review of scientific reports on herbal products for wound management, including phytochemical profiling and molecular modeling.","limitations":"The review is based on existing literature and may not include all relevant studies. Results from in-silico studies may not fully translate to clinical outcomes."},{"rthcId":"RPEP-06350","title":"Spinal cord-wide structural disruption in type 2 diabetes rescued by exenatide \"a glucagon-like peptide-1 analogue\" via down-regulating inflammatory, oxidative stress and apoptotic signaling pathways.","authors":"Mandour, Dalia A; Shalaby, Sally M; Bendary, M A","year":2022,"journal":"Journal of chemical neuroanatomy, 121, 102079","doi":"10.1016/j.jchemneu.2022.102079","pmid":"35143896","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Diabetic rats showed comprehensive spinal cord disruption:\n- Behavioral: thermal hyperalgesia, mechanical allodynia, decreased locomotor activity\n- Metabolic: increased glucose, insulin, HbA1c, HOMA-IR; decreased insulin sensitivity\n- Inflammatory: increased IL-1β, NF-κB; decreased IL-10 and β-endorphin in spinal tissue\n- Oxidative: increased MDA; decreased SOD activity\n- Apoptotic: upregulated caspase-3 and Bax; downregulated Bcl-2\n- Neurotrophic: downregulated NGF and GDNF\n- Histological: structural changes, increased CD68+ microglia\n\nExenatide treatment (10 μg/kg SC twice daily for 2 weeks) restored most of these biomolecular, structural, and functional impairments, demonstrating comprehensive neuroprotection.","whyItMatters":"Diabetic neuropathy affects up to 50% of diabetic patients and is a leading cause of disability, pain, and reduced quality of life. Current treatments only manage pain without addressing the underlying nerve damage. This study shows that exenatide — already FDA-approved for diabetes — can actually rescue spinal cord tissue from diabetic damage through multiple protective mechanisms. If these results translate to humans, GLP-1 drugs could treat both the diabetes and its neuropathic complications simultaneously.","specificNumbers":"","methodology":"30 male rats in three groups: control, diabetic (high-fat diet 8 weeks + streptozotocin 25 mg/kg IP), and diabetic + exenatide (10 μg/kg SC twice daily for 2 weeks). Assessments included neurobehavioral sensory/motor tests, glycemic biomarkers, spinal cord histology and immunohistochemistry, tissue cytokine and oxidant/antioxidant measurements (ELISA), and RT-qPCR for apoptotic and neurotrophic gene expression.","limitations":"Preclinical rat study — results may not translate directly to human diabetic neuropathy. The STZ diabetes model is chemically induced and may not fully represent human T2DM neuropathy. Only 2 weeks of treatment in an acute model; human neuropathy develops over years. The 10-rat-per-group sample is small. Only exenatide was tested; other GLP-1RAs might differ. The degree to which spinal cord changes versus peripheral nerve changes drive symptoms was not distinguished."},{"rthcId":"RPEP-06351","title":"Synthetic Proteins behind the Plasma Barrier: Molecular Spies.","authors":"Mann, Guy; Sadhu, Pradeep; Brik, Ashraf","year":2022,"journal":"Accounts of chemical research, 55(15), 2055-2067","doi":"10.1021/acs.accounts.2c00236","pmid":"35833291","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review highlights two main delivery strategies compatible with synthetic proteins: cell-penetrating peptides (CPPs) and multiplexed bead loading (MBL). CPPs are short peptide sequences that can transport synthetic proteins across the cell membrane, while MBL uses physical methods to introduce proteins into cells.\n\nThese delivery methods enable the study of posttranslational modifications (PTMs) — chemical changes that happen to proteins after they are made — in living cells. This is significant because PTMs regulate critical cellular processes but cannot be precisely controlled through genetic manipulation alone. The authors demonstrate applications including tracking protein localization, degradation, folding, interactions, and involvement in liquid-liquid phase separation organelles.","whyItMatters":"Many diseases involve errors in how proteins are chemically modified after they are made. Understanding these modifications requires studying custom-built proteins inside living cells — something genetic tools cannot fully achieve. By advancing delivery methods, particularly using cell-penetrating peptides, this field opens new possibilities for understanding disease mechanisms and potentially developing targeted therapies.","specificNumbers":"","methodology":"This is a review article (Account) in which the authors survey recent developments in protein delivery methods, evaluate their compatibility with chemically synthesized proteins, and describe their own work using cell-penetrating peptides and multiplexed bead loading. The review compares strengths and weaknesses of different delivery approaches for both protein introduction and subsequent biological studies.","limitations":"As a review article, this paper synthesizes existing work rather than presenting new experimental data. The delivery methods discussed still face challenges including limited efficiency, potential cytotoxicity, and difficulty achieving consistent delivery across different cell types. Many of the applications described are still in early research stages and have not been validated in therapeutic contexts."},{"rthcId":"RPEP-06352","title":"Carboxymethylcellulose biofunctionalized ternary quantum dots for subcellular-targeted brain cancer nanotheranostics.","authors":"Mansur, Alexandra A P; Paiva, Mayara R B; Cotta, Oliver A L; Silva, Luciana M; Carvalho, Isadora C; Capanema, Nádia S V; Carvalho, Sandhra M; Costa, Érica A; Martin, Nelson R; Ecco, Roselene; Santos, Beatriz S; Fialho, Silvia L; Lobato, Zélia I P; Mansur, Herman S","year":2022,"journal":"International journal of biological macromolecules, 210, 530-544","doi":"10.1016/j.ijbiomac.2022.04.207","pmid":"35513094","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Hybrid nanostructures combining carboxymethylcellulose (CMC), a pro-apoptotic KLA peptide, cell-penetrating cysteine, and fluorescent quantum dots (Ag-In-S) demonstrated superior performance against glioblastoma:\n\n- In vitro: the peptide-bearing nanoconjugates showed higher killing activity against U-87 MG glioblastoma cells than doxorubicin (a standard chemotherapy drug)\n- In vivo (CAM assay): the nanohybrids reduced glioblastoma tumor progression by 41% in area and showed antiangiogenic activity (inhibiting blood vessel formation that feeds tumors)\n- The nanostructures formed stable vesicle-like carriers suitable for both passive and active tumor targeting\n- Fluorescent properties enabled simultaneous bioimaging and intracellular tracking","whyItMatters":"Glioblastoma has a median survival of about 15 months with current treatments, which are limited by the difficulty of crossing the blood-brain barrier and severe systemic toxicity. A peptide-functionalized nanoparticle that simultaneously images tumors and kills cancer cells — while being less toxic than conventional chemotherapy — addresses multiple unmet needs in neuro-oncology. The use of a pro-apoptotic peptide rather than a small-molecule drug represents a fundamentally different therapeutic approach.","specificNumbers":"","methodology":"Novel hybrid nanostructures were designed by chemically functionalizing carboxymethylcellulose (CMC) with the mitochondria-targeting pro-apoptotic peptide KLA, cell-penetrating cysteine (CYS), and fluorescent Ag-In-S quantum dots (AIS). Nanoparticles were characterized for size, stability, and optical properties. In vitro cytotoxicity was tested against U-87 MG glioblastoma cells with comparison to doxorubicin. In vivo efficacy was evaluated using the chick chorioallantoic membrane (CAM) assay — a preclinical tumor model used to study drug effects on the tumor microenvironment.","limitations":"The CAM assay, while valuable as a preclinical model, does not fully replicate human brain tumor biology or the blood-brain barrier challenge. No mammalian animal models were used. Comparison to doxorubicin is useful but does not reflect current standard-of-care for glioblastoma (temozolomide + radiation). The nanoparticles' ability to cross the blood-brain barrier was not tested. Long-term toxicity, biodistribution, and pharmacokinetics in mammals are unknown. The quantum dots contain heavy metals (silver, indium) whose long-term biological safety needs evaluation."},{"rthcId":"RPEP-06353","title":"Exploration of bioactive peptides from various origin as promising nutraceutical treasures: In vitro, in silico and in vivo studies.","authors":"Manzoor, Mehnaza; Singh, Jagmohan; Gani, Adil","year":2022,"journal":"Food chemistry, 373(Pt A), 131395","doi":"10.1016/j.foodchem.2021.131395","pmid":"34710682","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Bioactive peptides exhibit multifunctional activities, including antioxidative and anticancer effects.","whyItMatters":"Understanding bioactive peptides can lead to new health-promoting foods and pharmaceuticals. This research could pave the way for innovative treatments for common health issues.","specificNumbers":"","methodology":"The study is a review that synthesizes existing research on bioactive peptides, including in vitro, in silico, and in vivo studies.","limitations":"As a review, it summarizes existing studies but does not provide new experimental data."},{"rthcId":"RPEP-06354","title":"Conus regius-Derived Conotoxins: Novel Therapeutic Opportunities from a Marine Organism.","authors":"Margiotta, Francesco; Micheli, Laura; Ciampi, Clara; Ghelardini, Carla; McIntosh, J Michael; Di Cesare Mannelli, Lorenzo","year":2022,"journal":"Marine drugs, 20(12)","doi":"10.3390/md20120773","pmid":"36547920","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"C. regius-derived conotoxins show high potency and selectivity against nicotinic acetylcholine receptors.","whyItMatters":"Understanding and improving conotoxins could lead to new treatments for serious conditions like pain and addiction. Their unique properties make them valuable for drug development.","specificNumbers":"","methodology":"The study provides an overview of the pharmacological features and molecular mechanisms of conotoxins, along with proposed chemical engineering solutions.","limitations":"The study highlights species-specific differences and the challenges of stability and bioavailability in clinical settings."},{"rthcId":"RPEP-06355","title":"Cross-presentation of a TAP-independent signal peptide induces CD8 T immunity to escaped cancers but necessitates anchor replacement.","authors":"Marijt, Koen A; Griffioen, Lisa; Blijleven, Laura; van der Burg, Sjoerd H; van Hall, Thorbald","year":2022,"journal":"Cancer immunology, immunotherapy : CII, 71(2), 289-300","doi":"10.1007/s00262-021-02984-7","pmid":"34142235","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The researchers identified that LRPAP1 signal peptide-specific CD8 T cells were present in the blood of all tested healthy donors and patients with non-small cell lung adenocarcinoma, confirming the immune system's inherent capacity to target this antigen.\n\nHowever, the natural peptide sequence was poorly presented by dendritic cells due to a weak-binding serine at the C-terminus. Replacing this serine with a valine dramatically improved HLA-A2 binding affinity and T cell stimulation. Critically, T cells primed with the valine-modified variant still recognized the natural serine version and responded to TAP-deficient cancer cells. A systematic screen of extended peptide variants identified a 24-mer N-terminally elongated synthetic long peptide as the optimal vaccine candidate, ready for clinical trial validation.","whyItMatters":"Cancer immune evasion is one of the biggest obstacles in immunotherapy. When tumors disable their TAP machinery, conventional T cell therapies lose their targets. This TEIPP vaccine approach flips the script — targeting antigens that only appear when cancers try to hide. Because these antigens are absent from healthy tissue, the vaccine could attack tumors with minimal risk of autoimmune side effects, potentially rescuing patients whose cancers have escaped standard immunotherapy.","specificNumbers":"","methodology":"The researchers developed synthetic long peptide variants from the LRPAP1 signal sequence and tested cross-presentation by monocyte-derived dendritic cells. They performed anchor residue substitution experiments, HLA-A2 binding assays, and tetramer staining to evaluate T cell specificity. A functional screen of N- and C-terminally extended peptide variants was conducted to identify the optimal vaccine format. T cells from healthy donors and non-small cell lung cancer patients were tested for reactivity against TAP-deficient tumor cells.","limitations":"This is preclinical research conducted in laboratory settings using cells from a limited number of donors and patients. The vaccine has not yet been tested in clinical trials, so its safety and effectiveness in actual cancer patients remain unknown. The study focused on HLA-A2-positive individuals, which represents only a subset of the population. Long-term durability of the induced T cell responses was not assessed."},{"rthcId":"RPEP-06356","title":"Self-Assembled Peptide Nanostructures for ECM Biomimicry.","authors":"Marin, Davide; Marchesan, Silvia","year":2022,"journal":"Nanomaterials (Basel, Switzerland), 12(13)","doi":"10.3390/nano12132147","pmid":"35807982","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Recent advancements have improved the incorporation of bioactive motifs into self-assembling peptides.","whyItMatters":"This research highlights a promising method for creating biomimetic materials that can aid in tissue engineering and regenerative medicine. It addresses the challenges of protein synthesis by offering a more efficient alternative.","specificNumbers":"","methodology":"The review analyzes literature from the past five years on peptide nanostructures and their applications.","limitations":"As a review, it does not present original experimental data and may not cover all recent advancements."},{"rthcId":"RPEP-06357","title":"Pancreatic islet cells disarray, apoptosis, and proliferation in obese mice. The role of Semaglutide treatment.","authors":"Marinho, Thatiany de Souza; Martins, Fabiane Ferreira; Cardoso, Luiz Eduardo de Macedo; Aguila, Marcia Barbosa; Mandarim-de-Lacerda, Carlos Alberto","year":2022,"journal":"Biochimie, 193, 126-136","doi":"10.1016/j.biochi.2021.10.017","pmid":"34742857","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06358","title":"Oral administration of VDAC1-derived small molecule peptides increases circulating testosterone levels in male rats.","authors":"Martinez-Arguelles, Daniel B; Nedow, Jennifer W; Gukasyan, Hovhannes J; Papadopoulos, Vassilios","year":2022,"journal":"Frontiers in endocrinology, 13, 1003017","doi":"10.3389/fendo.2022.1003017","pmid":"36686419","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The biologically active core of the VDAC1 cholesterol transport-enhancing peptide was identified as the tetrapeptide RVTQ. From this core, synthetic oral derivatives were designed, with 11 showing activity and 4 demonstrating robust, specific androgen increases. The lead compound RdVTQ was profiled across the lifespan of Brown-Norway rats and increased testosterone levels. The mechanism works within the HPG axis, meaning the body's natural feedback system self-regulates the response — preventing testosterone from rising to supraphysiological (abuse-potential) levels. Both subcutaneous and oral administration routes were effective.","whyItMatters":"Testosterone deficiency (hypogonadism) affects millions of men and currently requires injectable testosterone or topical gels, both of which bypass the body's natural regulatory system and carry risks of abuse and cardiovascular side effects. An oral peptide that works by enhancing the body's own testosterone production — with built-in self-regulation — could represent a fundamentally safer approach. The fact that it's a small peptide (4 amino acids) makes oral bioavailability achievable.","specificNumbers":"","methodology":"First, a subcutaneous delivery model for the parent peptide TV159-172 was established to study HPG axis interactions and identify the active core. The tetrapeptide RVTQ was identified as the minimal active sequence. Synthetic oral derivatives were designed and tested in a second animal model. Dose-response experiments identified the 4 most active compounds. The lead compound RdVTQ was profiled across the lifespan of Brown-Norway rats (a standard aging model). Circulating testosterone and related hormones were measured.","limitations":"All experiments in rats — human translation is uncertain, particularly regarding oral bioavailability of peptides in human GI tract. The self-regulation claim via HPG axis needs verification in longer-term and higher-dose studies. The Brown-Norway rat is a specific aging model that may not represent all human testosterone deficiency patterns. Manufacturing and stability of small peptides for oral formulation need assessment. No safety/toxicology data beyond testosterone-specific endpoints were reported. The mechanism assumes VDAC1-mediated cholesterol transport is similarly rate-limiting in humans."},{"rthcId":"RPEP-06359","title":"Systemic gene therapy with thymosin β4 alleviates glomerular injury in mice.","authors":"Mason, William J; Jafree, Daniyal J; Pomeranz, Gideon; Kolatsi-Joannou, Maria; Rottner, Antje K; Pacheco, Sabrina; Moulding, Dale A; Wolf, Anja; Kupatt, Christian; Peppiatt-Wildman, Claire; Papakrivopoulou, Eugenia; Riley, Paul R; Long, David A; Vasilopoulou, Elisavet","year":2022,"journal":"Scientific reports, 12(1), 12172","doi":"10.1038/s41598-022-16287-z","pmid":"35842494","tags":[],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"Gene therapy delivering thymosin beta-4 (TB4) — an actin-regulating peptide — prevented kidney damage in mice. When kidney-filtering cells (podocytes) were injured by the chemotherapy drug Adriamycin, TB4 levels in those cells dropped. Delivering TB4 via an adeno-associated viral vector increased circulating TB4 levels and prevented both podocyte loss and protein leakage into urine (albuminuria).\n\nThe protective mechanism was traced to TB4's ability to stabilize the actin cytoskeleton — the internal scaffolding that gives podocytes their unique shape. When Adriamycin disrupted this scaffolding in cell culture, adding TB4 restored its organization. The study also confirmed via single-cell RNA sequencing that injured podocytes specifically lose TB4 expression.","whyItMatters":"Podocytes are irreplaceable kidney cells — once they're lost, they don't regenerate, and their loss is the central event in many forms of kidney disease that progress to kidney failure. Currently, there's no approved therapy that directly protects podocytes. This study shows that TB4 gene therapy can prevent podocyte injury by maintaining their structural integrity, offering a fundamentally new approach to treating glomerular diseases that affect millions of people worldwide.","specificNumbers":"ADR injury reduced podocyte TB4 levels · AAV-TB4 increased circulating TB4 · podocyte loss prevented · albuminuria prevented · actin cytoskeleton organization restored in vitro · single-cell RNA-seq confirmed podocyte-specific TB4 loss","methodology":"Animal study with in vitro validation. Mice received Adriamycin (ADR) to induce podocyte injury. An adeno-associated viral (AAV) vector encoding TB4 was administered systemically. Researchers used single-cell RNA sequencing of isolated glomeruli, measured podocyte numbers, assessed albuminuria, and examined actin cytoskeleton organization in cultured podocytes treated with ADR and exogenous TB4.","limitations":"Adriamycin-induced nephropathy is a toxic injury model — it may not fully represent human glomerular diseases caused by autoimmunity, diabetes, or genetic mutations. AAV gene therapy has its own translational challenges (immune response, durability, manufacturing). The study assessed prevention rather than reversal of established injury. Long-term effects of sustained TB4 overexpression were not evaluated."},{"rthcId":"RPEP-06360","title":"The role of Kisspeptin signaling in Oocyte maturation.","authors":"Masumi, Saeed; Lee, Eun Bee; Dilower, Iman; Upadhyaya, Sameer; Chakravarthi, V Praveen; Fields, Patrick E; Rumi, M A Karim","year":2022,"journal":"Frontiers in endocrinology, 13, 917464","doi":"10.3389/fendo.2022.917464","pmid":"36072937","tags":["kisspeptin","reproductive-health"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Kisspeptin plays a dual role in oocyte maturation. The well-known indirect pathway works through the brain: hypothalamic kisspeptin neurons stimulate GnRH release, which triggers FSH and LH secretion from the pituitary, driving follicle development and ovulation.\n\nBut this review highlights a newer finding: kisspeptin also acts directly on the oocyte itself. Kisspeptins are produced by granulosa cells in ovarian follicles, while kisspeptin receptors are expressed on the oocytes. In mice, loss of kisspeptin receptors in oocytes led to failure of oocyte maturation and ovulation, resembling premature ovarian insufficiency.\n\nIn vitro studies in rats, pigs, and sheep confirmed that kisspeptin directly stimulates oocyte maturation by triggering calcium release and activating ERK1/2 signaling. In human clinical trials, kisspeptin-54 has been successfully used to improve oocyte maturation in assisted reproductive technologies.","whyItMatters":"The discovery that kisspeptin acts directly on eggs — not just through the brain — opens a new therapeutic avenue for fertility treatment. In IVF, triggering final egg maturation is a critical step that currently uses drugs with side effect risks. Kisspeptin offers a potentially safer trigger that works through both central and ovarian pathways, and clinical trials have already shown success in human patients undergoing assisted reproduction.","specificNumbers":"KP-54 used in human clinical trials · Mouse KPR knockout = ovulation failure · Ca²⁺ release + ERK1/2 activation in rat oocytes · KP expression peaks during preovulatory surge","methodology":"Narrative review synthesizing published research on kisspeptin signaling in oocyte maturation across species (mice, rats, pigs, sheep, humans). Covers both the indirect hypothalamic-pituitary pathway and the direct ovarian kisspeptin-oocyte signaling axis. Includes evidence from knockout studies, in vitro oocyte maturation experiments, and human clinical trials.","limitations":"As a review, no new experimental data is presented. Much of the direct ovarian kisspeptin evidence comes from animal models, and the relative contribution of direct vs. indirect kisspeptin signaling during in vivo human oocyte maturation is not fully resolved. Clinical trial data on kisspeptin-54 in assisted reproduction is still limited in scale."},{"rthcId":"RPEP-06361","title":"Long-acting amylin analogues for the management of obesity.","authors":"Mathiesen, David S; Bagger, Jonatan I; Knop, Filip K","year":2022,"journal":"Current opinion in endocrinology, diabetes, and obesity, 29(2), 183-190","doi":"10.1097/MED.0000000000000716","pmid":"35066542","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Cagrilintide has shown promising weight loss effects in early-stage trials.","whyItMatters":"These treatments could offer new options for obesity management, addressing a significant public health issue. Understanding their long-term effects is crucial for their successful implementation.","specificNumbers":"","methodology":"The study summarizes findings from preclinical and early-stage clinical trials of long-acting amylin analogues.","limitations":"The study primarily reviews early-stage research, and long-term effects in diverse populations remain unclear."},{"rthcId":"RPEP-06362","title":"Exit Interviews Examining the Patient Experience in Clinical Trials of Tirzepatide for Treatment of Type 2 Diabetes.","authors":"Matza, Louis S; Stewart, Katie D; Landó, Laura Fernández; Patel, Hiren; Boye, Kristina S","year":2022,"journal":"The patient, 15(3), 367-377","doi":"10.1007/s40271-022-00578-8","pmid":"35513765","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"100% of participants reported at least one treatment benefit, with 96% noting improved glycemic control and 93% weight loss.","whyItMatters":"Understanding patient experiences can enhance the evaluation of new treatments and guide future clinical practices. The insights gained from these interviews highlight the real-world impact of medications on quality of life.","specificNumbers":"","methodology":"Telephone interviews were conducted with 28 patients after completing trials, using a semi-structured guide and analyzed through content analysis.","limitations":"The study's sample size was small, and results may not be generalizable to all patients with type 2 diabetes."},{"rthcId":"RPEP-06363","title":"Orexin, serotonin, and energy balance.","authors":"Mavanji, Vijayakumar; Pomonis, Brianna; Kotz, Catherine M","year":2022,"journal":"WIREs mechanisms of disease, 14(1), e1536","doi":"10.1002/wsbm.1536","pmid":"35023323","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies a specific orexin-serotonin axis running from the lateral hypothalamus to the dorsal raphe nucleus that co-regulates three key components of energy balance: food intake, spontaneous physical activity (SPA), and energy expenditure.\n\nOrexin neurons in the lateral hypothalamus project to serotonin-producing neurons in the dorsal raphe nucleus, which then influence cortical and subcortical regions controlling movement, feeding, and calorie burning. The review also discusses how impaired serotonin function in animal obesity models, genetic variants in the serotonin system, and serotonin-targeting drugs (including SSRIs and uptake inhibitors) all affect obesity risk and treatment.","whyItMatters":"Most obesity research focuses on diet and intentional exercise, but spontaneous physical activity — all the small movements you do without thinking — actually burns significant calories. This review highlights that the brain has dedicated circuits controlling this 'NEAT' (non-exercise activity thermogenesis), and that the orexin-serotonin connection could be a druggable target. Understanding this axis could lead to entirely new approaches to obesity that work by increasing unconscious calorie burning rather than suppressing appetite.","specificNumbers":"","methodology":"This is a comprehensive narrative review synthesizing evidence from animal lesion and stimulation studies, neuroanatomical tracing studies, pharmacological experiments, genetic association studies, and clinical observations on serotonin-related drugs and obesity.","limitations":"As a narrative review, no new data is presented. Much of the evidence for the orexin-serotonin axis comes from rodent studies, and translating brain circuit manipulations to safe human therapeutics remains challenging. The review does not systematically assess study quality. The concept of pharmacologically boosting spontaneous activity remains largely theoretical."},{"rthcId":"RPEP-06364","title":"GLP-1 and GIP receptor signaling in beta cells - A review of receptor interactions and co-stimulation.","authors":"Mayendraraj, Ashok; Rosenkilde, Mette M; Gasbjerg, Lærke S","year":2022,"journal":"Peptides, 151, 170749","doi":"10.1016/j.peptides.2022.170749","pmid":"35065096","tags":["glp-1-receptor-agonists"],"studyType":"review","evidenceStrength":"review","keyFinding":"GLP-1 and GIP receptors in pancreatic beta cells share overlapping but distinct signaling pathways, both converging on cAMP to stimulate glucose-dependent insulin secretion. The review maps how tirzepatide — the first clinically successful dual GLP-1/GIP receptor agonist — exploits both pathways simultaneously.\n\nA key mechanistic insight: tirzepatide acts as a biased agonist at the GLP-1 receptor (activating some signaling pathways more than others) while potently activating the GIP receptor. This combination of biased GLP-1R signaling plus full GIPR activation may explain tirzepatide's superior clinical performance over GLP-1-only drugs.","whyItMatters":"Tirzepatide has shown better blood sugar control and weight loss than any single GLP-1 drug, but the molecular reasons weren't fully understood. This review provides a detailed map of how GLP-1 and GIP receptors signal in beta cells and interprets what happens when both are activated simultaneously. Understanding these mechanisms is essential for designing even better next-generation dual and triple agonists.","specificNumbers":"2 class B1 GPCRs reviewed · Both signal through cAMP · Tirzepatide = biased GLP-1R + potent GIPR agonism · 4 marketed GLP-1R agonists discussed (dulaglutide, liraglutide, exenatide, semaglutide)","methodology":"Narrative review of published literature on GLP-1R and GIPR signaling pathways in pancreatic beta cells, with focus on shared pathways, receptor interactions, and implications for co-agonist drug design.","limitations":"Review article — no new experimental data. The in vivo implications of dual receptor co-activation are difficult to isolate experimentally. Much of the mechanistic understanding comes from cell-based assays that may not fully reflect beta cell behavior in a living organism. The rapidly evolving field means some conclusions may need updating as new data emerge."},{"rthcId":"RPEP-06365","title":"Assessment of Reward-Related Brain Function After a Single Dose of Oxytocin in Autism: A Randomized Controlled Trial.","authors":"Mayer, Annalina V; Preckel, Katrin; Ihle, Kristin; Piecha, Fabian A; Junghanns, Klaus; Reiche, Stefan; Rademacher, Lena; Müller-Pinzler, Laura; Stolz, David S; Kamp-Becker, Inge; Stroth, Sanna; Roepke, Stefan; Küpper, Charlotte; Engert, Veronika; Singer, Tania; Kanske, Philipp; Paulus, Frieder M; Krach, Sören","year":2022,"journal":"Biological psychiatry global open science, 2(2), 136-146","doi":"10.1016/j.bpsgos.2021.10.004","pmid":"36325162","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In a randomized, double-blind, placebo-controlled crossover study of 37 men with autism and 37 controls, a single 24-IU dose of intranasal oxytocin did not significantly influence neural processes related to the anticipation of social or monetary rewards in either group.\n\nBayesian analyses provided moderate evidence favoring the null model over the alternative, suggesting the lack of effect is likely genuine rather than a power issue. Results were inconclusive regarding possible oxytocin effects on amygdala responsiveness to social rewards during reward consumption. Notably, there were no significant differences in reward-related brain function between autism and control groups under placebo either.","whyItMatters":"Oxytocin has been widely promoted as a potential treatment for social difficulties in autism, partly based on its role in social bonding. This well-designed negative study is important because it provides rigorous evidence against the hypothesis that single-dose oxytocin broadly enhances reward circuitry in autism, helping to set realistic expectations and redirect research toward more targeted approaches.","specificNumbers":"","methodology":"This was a randomized, double-blind, placebo-controlled, crossover fMRI study. Participants received either 24 IU intranasal oxytocin or placebo in separate sessions and performed an incentive delay task measuring neural activity during anticipation and receipt of both monetary and social rewards. Both frequentist and Bayesian statistical analyses were used to evaluate results.","limitations":"The study tested only a single dose, so chronic oxytocin effects remain unknown. Only men without intellectual impairment were included, limiting generalizability to women and those with co-occurring intellectual disability. The sample size (37 per group), while reasonable, may still have been insufficient to detect subtle effects. The incentive delay task may not capture all aspects of social reward processing relevant to autism."},{"rthcId":"RPEP-06366","title":"Targeting Protein Interaction Hotspots Using Structured and Disordered Chimeric Peptide Inhibitors.","authors":"Mayer, Guy; Shpilt, Zohar; Kowalski, Hadar; Tshuva, Edit Y; Friedler, Assaf","year":2022,"journal":"ACS chemical biology, 17(7), 1811-1823","doi":"10.1021/acschembio.2c00177","pmid":"35758642","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The chimeric peptide showed higher binding affinity and an IC50 of 10 ± 1 μM against A2780 cancer cells.","whyItMatters":"This research addresses a significant challenge in cancer treatment by developing a strategy to inhibit complex protein interactions. It could lead to new therapeutic options for targeting cancer more effectively.","specificNumbers":"","methodology":"The study involved designing chimeric peptides that combine structured and disordered elements to target protein interaction hotspots, followed by testing their binding affinity and cytotoxic effects on cancer cells.","limitations":"The study primarily focuses on in vitro experiments, and further research is needed to assess the effectiveness in vivo and in clinical settings."},{"rthcId":"RPEP-06367","title":"Characterization of New Defensin Antimicrobial Peptides and Their Expression in Bed Bugs in Response to Bacterial Ingestion and Injection.","authors":"Meraj, Sanam; Dhari, Arshvir Singh; Mohr, Emerson; Lowenberger, Carl; Gries, Gerhard","year":2022,"journal":"International journal of molecular sciences, 23(19)","doi":"10.3390/ijms231911505","pmid":"36232802","tags":["defensins","antimicrobial-peptides"],"studyType":"laboratory-study","evidenceStrength":"moderate","keyFinding":"Researchers identified four bed bug defensins (CL-defensin1, 2, 3a, and 3b) with highly conserved amino acid sequences, differing mainly in their signal and pro-peptide regions. When bed bugs were exposed to bacteria — either by injection or by feeding on blood containing bacteria — these defensins were upregulated in both the midgut and the rest of the body.\n\nFor the first time, the study demonstrated sex-specific and exposure-route-specific differences in defensin expression. Male and female bed bugs responded differently to the same bacterial challenge, and whether bacteria were injected or ingested produced distinct defensin activation patterns.\n\nThe responses also differed between Gram-positive (B. subtilis) and Gram-negative (E. coli) bacteria, showing the bed bug immune system can discriminate between bacterial types.","whyItMatters":"Bed bugs feed on human blood and carry pathogens, yet remarkably they don't transmit diseases to people — unlike mosquitoes and ticks. Their antimicrobial peptide defenses may be the key reason. By mapping which defensins activate in response to which bacteria, this study helps explain how bed bugs neutralize pathogens internally before they can be transmitted. This could inspire new antimicrobial peptide designs based on insect immune systems.","specificNumbers":"4 defensins characterized · 2 bacteria tested (Gram+ and Gram-) · 2 exposure routes (injection and ingestion) · Sex-specific responses documented","methodology":"Researchers characterized four new bed bug defensins through molecular analysis, structural prediction, and phylogenetic comparison. They exposed male and female bed bugs to Gram-positive (B. subtilis) and Gram-negative (E. coli) bacteria via injection or blood meal ingestion. Defensin expression was measured in midguts and remaining body tissue using comparative transcriptomics and real-time quantitative PCR.","limitations":"Study is limited to one insect species (Cimex lectularius). Only two bacterial species were tested. The functional antimicrobial activity of the individual defensins was not directly tested (only gene expression was measured). The mechanism by which defensins prevent pathogen transmission to vertebrates remains indirect."},{"rthcId":"RPEP-06368","title":"Liraglutide, a glucagon-like peptide 1 receptor agonist, exerts analgesic, anti-inflammatory and anti-degradative actions in osteoarthritis.","authors":"Meurot, C; Martin, C; Sudre, L; Breton, J; Bougault, C; Rattenbach, R; Bismuth, K; Jacques, C; Berenbaum, F","year":2022,"journal":"Scientific reports, 12(1), 1567","doi":"10.1038/s41598-022-05323-7","pmid":"35091584","tags":["glp-1-agonists","anti-inflammatory"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Liraglutide — a GLP-1 receptor agonist primarily used for diabetes and weight loss — showed three distinct therapeutic effects against osteoarthritis in laboratory and animal experiments:\n\n1. **Pain relief**: Intra-articular injection of liraglutide reduced pain-related behavior in a mouse OA model, likely through GLP-1R-mediated anti-inflammatory activity.\n2. **Anti-inflammatory action**: Liraglutide dose-dependently decreased IL-6, PGE2, and nitric oxide secretion and inflammatory gene expression in cartilage cells and macrophages. It also shifted macrophages from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype.\n3. **Cartilage protection**: Liraglutide significantly decreased the activity of metalloproteinases and aggrecanases — enzymes responsible for breaking down cartilage.","whyItMatters":"Osteoarthritis affects hundreds of millions of people worldwide and has no disease-modifying drug treatment. Current options only manage symptoms. This study suggests that liraglutide — already FDA-approved and widely prescribed for other conditions — could address multiple aspects of OA simultaneously: pain, inflammation, and cartilage destruction. If confirmed in humans, this could represent an entirely new use for GLP-1 drugs.","specificNumbers":"Dose-dependent reduction in IL-6, PGE2, nitric oxide; decreased metalloproteinase and aggrecanase activity; M1→M2 macrophage polarization shift; pain reduction in sodium monoiodoacetate mouse OA model; GLP-1R-mediated mechanism","methodology":"The study combined in vitro and in vivo experiments. In cell culture, researchers tested liraglutide on chondrocytes (cartilage cells) and macrophages, measuring inflammatory markers, gene expression, and enzyme activity. In mice, they used the sodium monoiodoacetate model to induce OA-like joint damage, then administered liraglutide via intra-articular injection and assessed pain behavior.","limitations":"This is preclinical research using mouse models and cell cultures. Human osteoarthritis is more complex than chemically induced OA in mice. The drug was injected directly into the joint, which may not reflect how systemically administered liraglutide affects joints. Specific quantitative results (effect sizes, sample sizes) are not detailed in the abstract. No long-term safety data for this use."},{"rthcId":"RPEP-06369","title":"The Enteroendocrine System in Obesity.","authors":"Miedzybrodzka, Emily L; Reimann, Frank; Gribble, Fiona M","year":2022,"journal":"Handbook of experimental pharmacology, 274, 109-129","doi":"10.1007/164_2022_582","pmid":"35419621","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The enteroendocrine system is not markedly disrupted by high BMI or obesogenic diets.","whyItMatters":"Understanding how the enteroendocrine system functions in obesity can lead to new treatments for weight loss and related health conditions.","specificNumbers":"","methodology":"The study reviews the role of gut hormones in regulating digestion and insulin secretion.","limitations":"The study is primarily a review and may not include new experimental data."},{"rthcId":"RPEP-06370","title":"Effects of Kisspeptin Administration in Women With Hypoactive Sexual Desire Disorder: A Randomized Clinical Trial.","authors":"Mills, Edouard G; Sheridan, Rebecca; Byers, Alexander; Sherwood, Robin A; Alexander, Emma C; Bech, Paul; Wall, Matthew B; Mayneris-Perxachs, Jordi; Sherwood, Karolina; Sheridan, Alexander; Salem, Victoria; Owen, Benedict M; Clarke, Sophie A; Sheridan, Rupert; Sherwood, Robin; Dhillo, Waljit S","year":2022,"journal":"JAMA network open, 5(10), e2237002","doi":"10.1001/jamanetworkopen.2022.37002","pmid":"36287566","tags":["neuropeptides"],"studyType":"Randomized Double-Blind Placebo-Controlled Crossover Trial","evidenceStrength":"Strong","keyFinding":"Kisspeptin administration significantly modulated sexual brain processing in women with HSDD — the first time this has been demonstrated in a clinical population. Specifically, kisspeptin deactivated the left inferior frontal gyrus (involved in behavioral inhibition) and activated the right postcentral and supramarginal gyrus during exposure to sexual stimuli.\n\nBeyond brain imaging changes, kisspeptin produced measurable behavioral effects: women reported increased feelings of 'feeling sexy' compared to placebo. Increased activation of the posterior cingulate cortex with kisspeptin was associated with reduced sexual aversion — suggesting the peptide may help overcome the psychological barriers that characterize HSDD.","whyItMatters":"HSDD is the most common sexual dysfunction in women, yet there are very few approved treatments. This is the first RCT showing that kisspeptin — a peptide already known to influence sexual processing in men — can modulate the sexual brain circuits in women with clinically diagnosed low desire. The finding that kisspeptin reduced brain activity in inhibition-related areas while boosting self-reported sexual feelings suggests it works by releasing the 'brakes' on sexual desire rather than just pressing the 'accelerator.'","specificNumbers":"n=32 · Premenopausal women with HSDD · Double-blind placebo-controlled crossover · Left inferior frontal gyrus deactivation · Right postcentral/supramarginal gyrus activation · Posterior cingulate cortex activation correlated with reduced aversion · Increased 'feeling sexy' scores","methodology":"Thirty-two premenopausal women with diagnosed HSDD participated in a randomized, double-blind, placebo-controlled crossover trial. Each participant received both kisspeptin and placebo infusions on separate visits. Brain activity was measured using functional MRI while participants viewed sexual stimuli. Self-reported behavioral measures including feelings of sexiness and sexual aversion were collected.","limitations":"Limited to premenopausal women — effects in postmenopausal women with HSDD are unknown. The single-session crossover design assessed acute effects only; whether repeated kisspeptin administration produces lasting changes in sexual desire is untested. Brain imaging changes during fMRI may not translate directly to improved sexual behavior in real-world settings. The study measured brain responses to stimuli in a scanner, not actual sexual experiences."},{"rthcId":"RPEP-06371","title":"Invited review: Translating kisspeptin and neurokinin B biology into new therapies for reproductive health.","authors":"Mills, Edouard G; Dhillo, Waljit S","year":2022,"journal":"Journal of neuroendocrinology, 34(10), e13201","doi":"10.1111/jne.13201","pmid":"36262016","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Kisspeptin has been established as the master regulator of mammalian reproduction, controlling both puberty onset and ongoing fertility. Human studies confirm that kisspeptin administration stimulates physiological reproductive hormone secretion in healthy men and women, as well as in patients with common reproductive disorders.\n\nNeurokinin B (NKB), which works alongside kisspeptin in KNDy neurons (kisspeptin/neurokinin B/dynorphin neurons), has emerged as a therapeutic target for menopausal hot flashes, endometriosis, and uterine fibroids. NKB receptor antagonists are being developed as treatments for these conditions. Together, kisspeptin and NKB represent two complementary peptide-based approaches to managing reproductive health.","whyItMatters":"Current fertility treatments rely heavily on synthetic GnRH analogs and gonadotropin injections, which can cause side effects like ovarian hyperstimulation syndrome. Kisspeptin offers a more physiological alternative that stimulates the body's own hormone cascade. Meanwhile, NKB antagonists are already reaching late-stage clinical trials for menopause symptoms and gynecological conditions, positioning these reproductive neuropeptides as the basis for an entirely new class of therapies.","specificNumbers":"","methodology":"This is an invited narrative review synthesizing evidence from animal models, human physiological studies, and clinical trials involving kisspeptin and neurokinin B in reproductive health contexts.","limitations":"As a narrative review, this paper summarizes and interprets existing evidence rather than presenting new experimental data. The review focuses on kisspeptin and NKB while noting that dynorphin (the third KNDy peptide) also plays important roles that are less therapeutically developed. Some of the clinical applications discussed were still in early-stage trials at the time of writing."},{"rthcId":"RPEP-06372","title":"Structure-activity relationships of mitochondria-targeted tetrapeptide pharmacological compounds.","authors":"Mitchell, Wayne; Tamucci, Jeffrey D; Ng, Emery L; Liu, Shaoyi; Birk, Alexander V; Szeto, Hazel H; May, Eric R; Alexandrescu, Andrei T; Alder, Nathan N","year":2022,"journal":"eLife, 11","doi":"10.7554/eLife.75531","pmid":"35913044","tags":["mitochondrial-peptides","ss-31"],"studyType":"original-research","evidenceStrength":"moderate","keyFinding":"Researchers conducted the first detailed structure-activity analysis of mitochondria-targeted tetrapeptides — the class that includes SS-31 (elamipretide). They compared four peptide analogs that differ in their aromatic amino acid composition and sequence order. Using NMR and molecular dynamics, they produced the first structural models of this compound class, revealing that all analogs except SS-31 form compact reverse turn conformations when bound to membranes.\n\nAll four peptides bound cardiolipin-containing membranes (a key mitochondrial lipid), reached mitochondria in cell culture, and showed pharmacological activity in stress models. However, they differed significantly in membrane interactions, effects on membrane surface charge, and ability to restore mitochondrial function. The tryptophan-containing analog SPN10 showed the strongest membrane effects and greatest cell protection, suggesting tryptophan side chains may be optimal for this class of therapeutics.","whyItMatters":"SS-31 (elamipretide) is the most advanced mitochondria-targeted peptide therapeutic, currently in clinical trials for heart failure and mitochondrial diseases. But scientists haven't fully understood how these peptides work at a molecular level. This study provides the first structural models and systematic comparison of analogs, establishing a framework for designing more potent next-generation versions. The finding that SPN10 outperformed SS-31 in several measures suggests there's room to improve on the lead clinical compound.","specificNumbers":"4 tetrapeptide analogs compared · First NMR structural models for this class · SPN10 (tryptophan analog) showed greatest efficacy · All 4 peptides targeted mitochondria · Cardiolipin binding confirmed for all analogs","methodology":"Four tetrapeptide analogs with alternating cationic and aromatic residues were synthesized and compared. Structural characterization used Nuclear Magnetic Resonance (NMR) spectroscopy and molecular dynamics simulations to model peptide conformations in membrane-bound states. Membrane binding studies measured interactions with cardiolipin-containing model membranes. Cell culture assays in mammalian cells assessed mitochondrial targeting, cell permeability, mitochondrial membrane potential, ATP levels, and cell survival under serum withdrawal stress conditions.","limitations":"All experiments were conducted in vitro using model membranes and cell culture — no animal or human studies were included. The serum withdrawal stress model is a simplified representation of mitochondrial dysfunction that may not capture the complexity of mitochondrial diseases in living organisms. Only four analogs were tested, which is a small fraction of the possible sequence space. The study doesn't address in vivo pharmacokinetics, stability, or tissue distribution."},{"rthcId":"RPEP-06373","title":"MOTS-c, the Most Recent Mitochondrial Derived Peptide in Human Aging and Age-Related Diseases.","authors":"Mohtashami, Zahra; Singh, Mithalesh K; Salimiaghdam, Nasim; Ozgul, Mustafa; Kenney, M Cristina","year":2022,"journal":"International journal of molecular sciences, 23(19)","doi":"10.3390/ijms231911991","pmid":"36233287","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06374","title":"The effect of substance P and its specific antagonist (aprepitant) on the expression of MMP-2, MMP-9, VEGF, and VEGFR in ovarian cancer cells.","authors":"Momen Razmgah, Maryam; Ghahremanloo, Atefeh; Javid, Hossein; AlAlikhan, Abbas; Afshari, Amir-R; Hashemy, Seyed Isaac","year":2022,"journal":"Molecular biology reports, 49(10), 9307-9314","doi":"10.1007/s11033-022-07771-w","pmid":"35960409","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Substance P increased mRNA expression of MMP-2, MMP-9, VEGF, and VEGFR in A2780 ovarian cancer cells, promoting cell migration (confirmed by scratch assay) and angiogenic signaling. Blocking the NK1R receptor with aprepitant suppressed all of these Substance P-induced effects, reducing both migration-related and angiogenesis-related gene expression.\n\nThe findings establish a mechanistic link between the SP/NK1R signaling system and two key processes in ovarian cancer metastasis: cell migration (via matrix metalloproteinases) and new blood vessel formation (via VEGF/VEGFR pathway).","whyItMatters":"Ovarian cancer frequently metastasizes, and controlling its spread remains a major clinical challenge. Aprepitant is already FDA-approved and widely used to prevent chemotherapy-induced nausea, meaning its safety profile is well established. If its anti-cancer effects are confirmed in vivo and clinically, it could be quickly repurposed as an adjunct therapy — a much faster path than developing a new drug from scratch.","specificNumbers":"","methodology":"Researchers used A2780 ovarian cancer cells and performed resazurin assays to assess aprepitant's cytotoxic effects on cell viability. RT-PCR was used to measure mRNA expression of MMP-2, MMP-9, VEGF, and VEGFR after treatment with Substance P alone and in combination with aprepitant. Scratch assays were conducted to directly measure the effect on cell migration.","limitations":"The study was conducted entirely in vitro using a single ovarian cancer cell line (A2780), which may not represent the full diversity of ovarian cancers. No in vivo animal studies or clinical data were presented. Only mRNA expression was measured, not protein levels or functional pathway activation. The concentrations of Substance P and aprepitant used may not reflect physiological or pharmacological levels in patients."},{"rthcId":"RPEP-06375","title":"Rational design of a trypanocidal peptide derived from Dinoponera quadriceps venom.","authors":"Monteiro, Marília Lopes; Lima, Dânya Bandeira; Freire, Katielle Albuquerque; Nicolaski Pedron, Cibele; Magalhães, Emanuel Paula; Silva, Brenna Pinheiro; García-Jareño, Alicia Belén; De Oliveira, Cyntia Silva; Nunes, João Victor Serra; Marinho, Marcia Machado; Menezes, Ramon Róseo Paula Pessoa Bezerra de; Orzaéz, Mar; Oliveira Junior, Vani Xavier; Martins, Alice Maria Costa","year":2022,"journal":"European journal of medicinal chemistry, 241, 114624","doi":"10.1016/j.ejmech.2022.114624","pmid":"35933786","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Two smaller peptides, M-PONTX-Dq3a [1-15] and [Lys]3-M-PONTX-Dq3a [3-15], showed similar trypanocidal activity to the parent peptide.","whyItMatters":"Chagas disease affects millions and current treatments are inadequate, especially for chronic cases. These new peptides could lead to more effective therapies.","specificNumbers":"","methodology":"The study involved isolating peptide fragments from M-PONTX-Dq3a and testing their effectiveness against T. cruzi.","limitations":"The study primarily focuses on peptide fragments in vitro, and further research is needed to assess their efficacy in clinical settings."},{"rthcId":"RPEP-06376","title":"GLP-1 Receptor Agonists in Neurodegeneration: Neurovascular Unit in the Spotlight.","authors":"Monti, Giulia; Gomes Moreira, Diana; Richner, Mette; Mutsaers, Henricus Antonius Maria; Ferreira, Nelson; Jan, Asad","year":2022,"journal":"Cells, 11(13)","doi":"10.3390/cells11132023","pmid":"35805109","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 receptor agonists show promise as neuroprotective agents in models of AD and PD.","whyItMatters":"Finding effective treatments for neurodegenerative diseases is crucial as current therapies mainly address symptoms. Understanding the mechanisms of GLP-1 receptor agonists could lead to new therapeutic strategies.","specificNumbers":"","methodology":"The review synthesizes existing research on GLP-1 receptor agonists in cellular and animal models of neurodegeneration.","limitations":"The review is based on existing studies, primarily in animal models, which may not fully translate to human conditions."},{"rthcId":"RPEP-06377","title":"Antimicrobial Proteins and Peptides in Avian Eggshell: Structural Diversity and Potential Roles in Biomineralization.","authors":"Moreau, Thierry; Gautron, Joël; Hincke, Maxwell T; Monget, Philippe; Réhault-Godbert, Sophie; Guyot, Nicolas","year":2022,"journal":"Frontiers in immunology, 13, 946428","doi":"10.3389/fimmu.2022.946428","pmid":"35967448","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The study identifies over 900 matrix proteins in chicken eggshells, including various antimicrobial proteins.","whyItMatters":"Understanding the roles of these proteins can enhance knowledge of avian biology and improve egg safety and quality in agriculture.","specificNumbers":"","methodology":"This is a review study that compiles and analyzes existing research and databases on avian eggshell proteins.","limitations":"The review primarily focuses on chicken eggshells, which may limit the generalizability of findings to other species."},{"rthcId":"RPEP-06378","title":"Impact of semaglutide on high-sensitivity C-reactive protein: exploratory patient-level analyses of SUSTAIN and PIONEER randomized clinical trials.","authors":"Mosenzon, Ofri; Capehorn, Matthew S; De Remigis, Alessandra; Rasmussen, Søren; Weimers, Petra; Rosenstock, Julio","year":2022,"journal":"Cardiovascular diabetology, 21(1), 172","doi":"10.1186/s12933-022-01585-7","pmid":"36056351","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across all four trials, semaglutide significantly reduced hsCRP versus comparators with estimated treatment ratios of 0.70-0.76 (meaning 24-30% greater reduction; p < 0.05). This held true when analyzed by clinical cutoffs and by baseline hsCRP tertiles, showing benefit across the inflammation spectrum.\n\nMediation analysis revealed that changes in HbA1c and body weight accounted for only 20.6-61.8% of semaglutide's CRP-lowering effect, suggesting a substantial direct anti-inflammatory action. In PIONEER 5 (the chronic kidney disease trial), the CRP reduction was not statistically significant versus comparators, indicating the anti-inflammatory effect may be attenuated in CKD. Baseline hsCRP ranged from 2.7-3.0 mg/L across trials, placing this population at elevated cardiovascular risk.","whyItMatters":"Inflammation is increasingly recognized as a driver of cardiovascular events in diabetes — not just blood sugar or cholesterol. Finding that semaglutide has anti-inflammatory properties beyond its metabolic effects helps explain the cardiovascular benefits seen in the SUSTAIN-6 and SELECT trials. If semaglutide directly reduces inflammation, it positions GLP-1 drugs as multi-mechanism cardiovascular protectors, not just glucose-lowering agents.","specificNumbers":"","methodology":"This was an exploratory patient-level analysis of four randomized clinical trials: SUSTAIN 3 (subcutaneous semaglutide vs exenatide ER), PIONEER 1 (oral semaglutide vs placebo), PIONEER 2 (oral semaglutide vs empagliflozin), and PIONEER 5 (oral semaglutide vs placebo in CKD). The combined analysis included 2,482 patients with type 2 diabetes (1,328 semaglutide, 339 placebo, 405 exenatide ER, 410 empagliflozin). hsCRP was analyzed as ratio to baseline at end-of-treatment, by clinical cutoffs, and by mediation analysis assessing HbA1c and body weight contributions.","limitations":"This was an exploratory post-hoc analysis of clinical trial data, not a prospectively designed inflammation study. The CRP reduction was not significant in the CKD subgroup (PIONEER 5), which may reflect the population or the smaller sample. Different comparators across trials (placebo, exenatide, empagliflozin) complicate direct comparisons. The mediation analysis cannot definitively prove direct anti-inflammatory mechanisms. Longer-term CRP data and clinical inflammation endpoints were not assessed."},{"rthcId":"RPEP-06379","title":"Level of therapeutic innovation from the registration studies of the new drugs for the prophylaxis of migraine.","authors":"Motola, Domenico; Santi Laurini, Greta; Bonaldo, Giulia; Montanaro, Nicola","year":2022,"journal":"Journal of clinical pharmacy and therapeutics, 47(12), 2130-2139","doi":"10.1111/jcpt.13760","pmid":"36054749","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"All new drugs showed only a modest level of therapeutic innovation according to the assessment algorithm.","whyItMatters":"Understanding the true innovation level of new migraine treatments helps guide clinical decisions and patient expectations. It also highlights the need for more effective therapies.","specificNumbers":"","methodology":"The study analyzed data from European public assessment reports and used a previously published algorithm to assess therapeutic innovation.","limitations":"The study only compared new drugs against placebo, not against existing treatments, limiting the understanding of their relative effectiveness."},{"rthcId":"RPEP-06380","title":"Glyphosate induces immune dysregulation in honey bees.","authors":"Motta, Erick V S; Powell, J Elijah; Moran, Nancy A","year":2022,"journal":"Animal microbiome, 4(1), 16","doi":"10.1186/s42523-022-00165-0","pmid":"35193702","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Glyphosate exposure decreased antimicrobial peptide expression and inhibited melanization in honey bees.","whyItMatters":"Understanding how agrochemicals like glyphosate affect bee immunity is crucial for bee health and ecosystem stability. This research could inform better agricultural practices to protect pollinators.","specificNumbers":"","methodology":"The study compared the effects of glyphosate and tylosin on honey bee immune responses by measuring gene expression and immune pathways.","limitations":"The study primarily focuses on laboratory conditions, which may not fully replicate natural environments for honey bees."},{"rthcId":"RPEP-06381","title":"Potential in vitro therapeutic effects of targeting SP/NK1R system in cervical cancer.","authors":"Mozafari, Mahtab; Ebrahimi, Safieh; Darban, Reza Assaran; Hashemy, Seyed Isaac","year":2022,"journal":"Molecular biology reports, 49(2), 1067-1076","doi":"10.1007/s11033-021-06928-3","pmid":"34766230","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Aprepitant reduced HeLa cell viability in a dose and time-dependent manner.","whyItMatters":"Understanding the SP/NK1R system's role in cervical cancer could lead to innovative treatments that improve patient outcomes.","specificNumbers":"","methodology":"The study utilized colorimetric MTT assays, qRT-PCR, flow cytometry, and wound-healing assays to analyze cell behavior.","limitations":"The study was conducted in vitro, so results may not directly translate to human patients."},{"rthcId":"RPEP-06382","title":"Screening and Mechanism of Novel Angiotensin-I-Converting Enzyme Inhibitory Peptides in X. sorbifolia Seed Meal: A Computer-Assisted Experimental Study Method.","authors":"Mu, Yihan; Liu, Dongwei; Xie, Huaping; Zhang, Xinyu; Han, Xue; Lv, Zhaolin","year":2022,"journal":"Molecules (Basel, Switzerland), 27(24)","doi":"10.3390/molecules27248792","pmid":"36557925","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The peptides GGLPGFDPA and ETYFIVR showed ACE inhibition rates of 24.89% and 67.02% at 0.1 mg/mL, respectively.","whyItMatters":"Identifying new ACE inhibitors can lead to better treatments for hypertension, a major health issue worldwide. This research highlights the potential of plant-based sources for developing these therapeutic peptides.","specificNumbers":"","methodology":"The study used computer-assisted screening and LC-MS/MS analysis to identify and evaluate peptides from X. sorbifolia seed meal.","limitations":"The study was conducted in vitro, and results may not directly translate to human applications."},{"rthcId":"RPEP-06383","title":"Cow and camel milk-derived whey and casein protein hydrolysates demonstrated effective antifungal properties against selected Candida species.","authors":"Mudgil, Priti; AlMazroui, May; Redha, Ali Ali; Kilari, Bhanu Priya; Srikumar, Shabarinath; Maqsood, Sajid","year":2022,"journal":"Journal of dairy science, 105(3), 1878-1888","doi":"10.3168/jds.2021-20944","pmid":"34955259","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Camel casein hydrolysate inhibited Candida albicans by 93.69%, outperforming fluconazole (76.92%).","whyItMatters":"Understanding the antifungal properties of milk proteins could lead to new treatments for fungal infections, especially as resistance to conventional antifungals increases.","specificNumbers":"","methodology":"The study involved producing protein hydrolysates from cow and camel milk using two enzymes and testing their antifungal effects against various Candida species.","limitations":"The study focused only on certain Candida species and did not assess the effects in human subjects, limiting the applicability of results."},{"rthcId":"RPEP-06384","title":"The Effect of Cerebrolysin on Anxiety, Depression, and Cognition in Moderate and Severe Traumatic Brain Injury Patients: A CAPTAIN II Retrospective Trial Analysis.","authors":"Mureșanu, Ioana Anamaria; Grad, Diana Alecsandra; Mureșanu, Dafin Fior; Hapca, Elian; Benedek, Irina; Jemna, Nicoleta; Strilciuc, Ștefan; Popescu, Bogdan Ovidiu; Perju-Dumbravă, Lăcrămioara; Cherecheș, Răzvan Mircea","year":2022,"journal":"Medicina (Kaunas, Lithuania), 58(5)","doi":"10.3390/medicina58050648","pmid":"35630065","tags":[],"studyType":"secondary-analysis","evidenceStrength":"moderate","keyFinding":"Cerebrolysin, a peptide preparation derived from pig brain tissue, significantly reduced anxiety in patients with moderate and severe traumatic brain injury (TBI) compared to placebo. Statistically significant differences in HADS-Anxiety scores were found at both the second and third follow-up visits, with a large effect size of 0.73.\n\nThe study also identified correlations between anxiety/depression scores and other neuropsychological measures, suggesting that post-TBI mental health is connected to cognitive and motor recovery. The patient sample had a mean age of 45.3, was primarily male, and had a 24-hour Glasgow Coma Scale mean of 12.67 (indicating moderate-to-severe injury).","whyItMatters":"Traumatic brain injury frequently causes depression, anxiety, and cognitive impairment that persist long after the initial injury. There are few treatments specifically designed for post-TBI psychiatric symptoms. The finding that Cerebrolysin — already used in some countries for neurological recovery — could significantly reduce post-TBI anxiety with a large effect size suggests it may address both the neurological and psychiatric consequences of brain injury.","specificNumbers":"n=125 · Effect size 0.73 (large) for anxiety · Mean age 45.3 · GCS mean 12.67 · Significant at visits 2 and 3 · HADS-Anxiety/Depression assessed","methodology":"This was a secondary retrospective analysis of the CAPTAIN II trial data. 125 TBI patients with moderate and severe disability were divided into two groups: Cerebrolysin treatment and saline placebo. Researchers used the Hospital Anxiety and Depression Scale (HADS) to measure psychiatric outcomes, Spearman's correlations to assess relationships between HADS and other neuropsychological scales, and Mann-Whitney U tests to compare anxiety and depression scores between treatment groups.","limitations":"This is a retrospective secondary analysis, not a prospectively designed psychiatric outcomes trial. The sample of 125 patients is moderate in size. The analysis was conducted post-hoc on an existing database, increasing the risk of finding spurious associations. The authors explicitly note that confirmatory trials are needed. Cerebrolysin is not FDA-approved and its mechanisms remain debated."},{"rthcId":"RPEP-06385","title":"Real-World Patient Experience of CGRP-Targeting Therapy for Migraine: a Narrative Review.","authors":"Murray, Ann M; Stern, Jennifer I; Robertson, Carrie E; Chiang, Chia-Chun","year":2022,"journal":"Current pain and headache reports, 26(10), 783-794","doi":"10.1007/s11916-022-01077-z","pmid":"36063264","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CGRP-targeting therapies showed meaningful effectiveness with response rates similar to clinical trials.","whyItMatters":"Understanding real-world effectiveness can help clinicians make informed treatment decisions for migraine patients. It also highlights the need for ongoing research into long-term outcomes and safety.","specificNumbers":"","methodology":"The study involved a narrative review of existing literature on CGRP-targeting therapies, analyzing patient characteristics and treatment outcomes.","limitations":"The review is based on existing studies, which may have variability in quality and reporting standards. Long-term data is lacking."},{"rthcId":"RPEP-06386","title":"Personalized therapy with peptide-based neoantigen vaccine (EVX-01) including a novel adjuvant, CAF®09b, in patients with metastatic melanoma.","authors":"Mørk, Sofie Kirial; Kadivar, Mohammad; Bol, Kalijn Fredrike; Draghi, Arianna; Westergaard, Marie Christine Wulff; Skadborg, Signe Koggersbøl; Overgaard, Nana; Sørensen, Anders Bundgård; Rasmussen, Ida Svahn; Andreasen, Lars Vibe; Yde, Christina Westmose; Trolle, Thomas; Garde, Christian; Friis-Nielsen, Jens; Nørgaard, Nis; Christensen, Dennis; Kringelum, Jens Vindahl; Donia, Marco; Hadrup, Sine Reker; Svane, Inge Marie","year":2022,"journal":"Oncoimmunology, 11(1), 2023255","doi":"10.1080/2162402X.2021.2023255","pmid":"35036074","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"EVX-01 elicited long-lasting T-cell responses in all five patients with no severe adverse events.","whyItMatters":"This research highlights the potential of personalized immunotherapy in treating melanoma, a challenging cancer type. The findings support further exploration of neoantigen vaccines in cancer treatment.","specificNumbers":"","methodology":"The study involved an interim analysis of five patients receiving six administrations of the personalized vaccine, with tumor neoantigens identified using an AI platform.","limitations":"The study is based on a small sample size and is an interim analysis, limiting the generalizability of the findings."},{"rthcId":"RPEP-06387","title":"Grafting Hydrophobic Amino Acids Critical for Inhibition of Protein-Protein Interactions on a Cell-Penetrating Peptide Scaffold.","authors":"Nagano, Yuki; Arafiles, Jan Vincent V; Kuwata, Keiko; Kawaguchi, Yoshimasa; Imanishi, Miki; Hirose, Hisaaki; Futaki, Shiroh","year":2022,"journal":"Molecular pharmaceutics, 19(2), 558-567","doi":"10.1021/acs.molpharmaceut.1c00671","pmid":"34958576","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Researchers grafted key hydrophobic amino acids (phenylalanine, tryptophan, leucine) onto a cell-penetrating peptide scaffold (CADY2) to create membrane-permeable protein-protein interaction inhibitors. While the resulting peptides (CADY-3FWL and CADY-10FWL) successfully killed cancer cells through apoptosis, they did not bind to their intended target (HDM2). Instead, proteomic analysis revealed they bound nesprin-2, a protein involved in shuttling β-catenin into the cell nucleus.\n\nThe peptides reduced nuclear β-catenin localization and decreased expression of anti-apoptotic genes in the Wnt signaling pathway — an unexpected but potentially valuable anticancer mechanism.","whyItMatters":"This study illustrates both the promise and complexity of peptide drug design. While the original target was missed, the serendipitous discovery of a mechanism that blocks β-catenin nuclear entry via nesprin-2 could open a new therapeutic avenue. The Wnt/β-catenin pathway is overactive in many cancers, and a cell-penetrating peptide that blocks this signaling represents a novel approach to cancer treatment.","specificNumbers":"3 critical amino acids grafted (Phe, Trp, Leu) · 2 peptide analogues created · Nesprin-2 identified as binding target · Decreased β-catenin nuclear localization · Reduced anti-apoptotic gene expression","methodology":"Researchers designed peptide analogues by grafting hydrophobic residues critical for p53-HDM2 inhibition onto the CADY2 cell-penetrating peptide framework. They tested cellular uptake, apoptosis induction, and HDM2 binding. When HDM2 binding was absent, they performed pull-down experiments with proteomic analysis to identify actual binding targets. β-catenin nuclear localization and downstream gene expression were measured to characterize the mechanism of action.","limitations":"The peptides failed to bind their intended target (HDM2), meaning the cell-penetrating PPI inhibitor strategy was not validated as designed. The newly discovered nesprin-2 mechanism requires further validation. All work was in vitro, and it is unclear whether these peptides would be stable, non-toxic, and effective in living organisms. The binding specificity to nesprin-2 and potential off-target effects need further characterization."},{"rthcId":"RPEP-06388","title":"Intrathecally administered substance P activated the spinal defecation center and enhanced colorectal motility in anesthetized rats.","authors":"Naitou, Kiyotada; Iwashita, Honoka; Ueda, Hiromi H; Shiraishi, Mitsuya; Fujimoto, Yoshikazu; Horii, Kazuhiro; Sawamura, Tomoya; Shiina, Takahiko; Shimizu, Yasutake","year":2022,"journal":"American journal of physiology. Gastrointestinal and liver physiology, 323(1), G21-G30","doi":"10.1152/ajpgi.00342.2021","pmid":"35470689","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Substance P enhanced colorectal motility in anesthetized rats, even after spinal cord transection.","whyItMatters":"Understanding how substance P influences bowel movements could lead to new treatments for gastrointestinal disorders. This research highlights the role of specific receptors in regulating defecation.","specificNumbers":"","methodology":"The study involved administering substance P intrathecally to anesthetized rats and measuring its effects on colorectal motility.","limitations":"The study was conducted in anesthetized rats, which may limit the applicability of results to conscious humans."},{"rthcId":"RPEP-06389","title":"Antimicrobial effect and mechanism of bovine lactoferrin against the potato common scab pathogen Streptomyces scabiei.","authors":"Nakamura, Masayuki; Tsuda, Naoaki; Miyata, Takeshi; Ikenaga, Makoto","year":2022,"journal":"PloS one, 17(2), e0264094","doi":"10.1371/journal.pone.0264094","pmid":"35213576","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Bovine lactoferrin showed a minimal inhibitory concentration of 3.9 μM against S. scabiei.","whyItMatters":"Understanding how bovine lactoferrin works against plant pathogens could lead to better crop protection strategies. This research may also inform the development of new antimicrobial agents.","specificNumbers":"","methodology":"The study involved testing the antimicrobial activity of bovine lactoferrin and its peptides against the pathogen in vitro.","limitations":"The study was conducted in vitro, and results may not directly translate to field conditions or human applications."},{"rthcId":"RPEP-06390","title":"Analysis of the interaction of cyclosporine congeners with cell membrane models.","authors":"Nakao, Mizuka; Takechi-Haraya, Yuki; Ohgita, Takashi; Saito, Hiroyuki; Demizu, Yosuke; Izutsu, Ken-Ichi; Sakai-Kato, Kumiko","year":2022,"journal":"Journal of pharmaceutical and biomedical analysis, 218, 114874","doi":"10.1016/j.jpba.2022.114874","pmid":"35696938","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Cyclosporine D had the highest internalization in HpG2 cells compared to A, B, and C.","whyItMatters":"Understanding how these peptides interact with cell membranes is crucial for developing effective drugs. The findings can guide the design of new macrocyclic peptides with improved properties.","specificNumbers":"","methodology":"The study used circular dichroism, fluorescence spectroscopy, and HPLC to analyze the interactions of cyclosporine congeners with cell membrane models.","limitations":"The study primarily focused on in vitro models, which may not fully represent in vivo conditions."},{"rthcId":"RPEP-06391","title":"Peptide hydrogels for affinity-controlled release of therapeutic cargo: Current and potential strategies.","authors":"Nambiar, Monessha; Schneider, Joel P","year":2022,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 28(1), e3377","doi":"10.1002/psc.3377","pmid":"34747114","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Affinity-based release strategies incorporate reversible molecular interactions into peptide hydrogel networks that bind and gradually release therapeutic cargo. These interactions can be tuned to control drug release profiles, meeting specific pharmacokinetic requirements. The review identifies this as an underexplored but promising approach in peptide hydrogels, which offer advantages over polymer-based systems including biocompatibility and biodegradability inherent to peptide materials.","whyItMatters":"Many therapeutic peptides and proteins have short half-lives, requiring frequent injections that reduce patient compliance and increase side effects. Peptide hydrogels that release drugs at controlled rates could enable single-injection treatments that maintain therapeutic levels for extended periods — a significant quality-of-life improvement for patients on chronic peptide therapies.","specificNumbers":"","methodology":"This is a review article surveying recent advances in affinity-controlled peptide gel release systems. It covers design principles, release mechanisms, and applications in drug delivery, comparing approaches used in polymer-based materials with emerging strategies in peptide hydrogels.","limitations":"This is a review without new experimental data. The field of affinity-controlled peptide hydrogels is still in early stages, with most work being proof-of-concept. Translation to clinical drug delivery products faces challenges in manufacturing scalability, regulatory approval, and demonstrating clinical superiority over existing controlled-release technologies."},{"rthcId":"RPEP-06392","title":"Tirzepatide, a dual GIP/GLP-1 receptor co-agonist for the treatment of type 2 diabetes with unmatched effectiveness regrading glycaemic control and body weight reduction.","authors":"Nauck, Michael A; D'Alessio, David A","year":2022,"journal":"Cardiovascular diabetology, 21(1), 169","doi":"10.1186/s12933-022-01604-7","pmid":"36050763","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tirzepatide reduced HbA1c by 1.24 to 2.58% and body weight by 5.4-11.7 kg.","whyItMatters":"This medication represents a significant advancement in diabetes treatment, potentially offering better management of blood sugar and weight. Understanding its mechanisms could lead to new therapies for diabetes and obesity.","specificNumbers":"","methodology":"Five clinical trials (SURPASS 1-5) were conducted with type 2 diabetes patients, comparing tirzepatide to other treatments.","limitations":"Further research is needed to fully understand tirzepatide's mechanisms and its long-term effects in humans."},{"rthcId":"RPEP-06393","title":"Complexes of Ghrelin GHS-R1a, GHS-R1b, and Dopamine D1 Receptors Localized in the Ventral Tegmental Area as Main Mediators of the Dopaminergic Effects of Ghrelin.","authors":"Navarro, Gemma; Rea, William; Quiroz, César; Moreno, Estefanía; Gomez, Devan; Wenthur, Cody J; Casadó, Vicent; Leggio, Lorenzo; Hearing, Matthew C; Ferré, Sergi","year":2022,"journal":"The Journal of neuroscience : the official journal of the Society for Neuroscience, 42(6), 940-953","doi":"10.1523/JNEUROSCI.1151-21.2021","pmid":"34876469","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GHS-R1a:GHS-R1b:D1R oligomers are the main mediators of ghrelin's dopaminergic effects in the rodent VTA.","whyItMatters":"Understanding the role of ghrelin in dopamine signaling could provide insights into motivation and behavior, potentially informing treatments for related disorders.","specificNumbers":"","methodology":"The study used mammalian cell transfection, ex vivo experiments, in vivo microdialysis, and patch-clamp electrophysiology to analyze receptor interactions and effects.","limitations":"The study primarily involved rodent models, which may not fully replicate human physiology."},{"rthcId":"RPEP-06394","title":"Thymosin alpha 1 as an adjuvant to hyperthermic intraperitoneal chemotherapy in an experimental model of peritoneal metastases from colonic carcinoma.","authors":"Nevo, Nadav; Lee Goldstein, Adam; Bar-David, Shoshi; Natanson, Maya; Alon, Gilad; Lahat, Guy; Nizri, Eran","year":2022,"journal":"International immunopharmacology, 111, 109166","doi":"10.1016/j.intimp.2022.109166","pmid":"35994852","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Mice treated with Tα1 had a survival rate of 16.1 days compared to 14.1 days for HIPEC alone and 11.8 days for sham treatment (p = 0.02).","whyItMatters":"This research highlights the potential of immunomodulatory treatments like Tα1 to enhance the effectiveness of existing chemotherapy methods. Improving survival rates in cancer treatment is crucial for patient outcomes.","specificNumbers":"","methodology":"The study used a mouse model of peritoneal metastases induced by colon cancer, comparing survival and immune responses between groups receiving HIPEC alone and those receiving HIPEC plus Tα1.","limitations":"The study was conducted in mice, and results may not directly translate to humans. Further research is needed to explore the long-term effects and optimal dosing of Tα1."},{"rthcId":"RPEP-06395","title":"Smp24, a Scorpion-Venom Peptide, Exhibits Potent Antitumor Effects against Hepatoma HepG2 Cells via Multi-Mechanisms In Vivo and In Vitro.","authors":"Nguyen, Tienthanh; Guo, Ruiyin; Chai, Jinwei; Wu, Jiena; Liu, Junfang; Chen, Xin; Abdel-Rahman, Mohamed A; Xia, Hu; Xu, Xueqing","year":2022,"journal":"Toxins, 14(10)","doi":"10.3390/toxins14100717","pmid":"36287985","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Smp24 reduced HepG2 cell viability significantly while sparing normal LO2 cells.","whyItMatters":"The findings highlight a potential new treatment option for hepatocellular carcinoma, which is often difficult to treat. Understanding the mechanisms of Smp24 could lead to more effective cancer therapies.","specificNumbers":"","methodology":"The study involved both in vitro experiments on HepG2 cells and in vivo tests using a HepG2 xenograft mouse model.","limitations":"The study primarily focuses on in vitro and animal models, which may not fully replicate human responses."},{"rthcId":"RPEP-06396","title":"Mannose and Hyaluronic Acid Dual-Modified Iron Oxide Enhances Neoantigen-Based Peptide Vaccine Therapy by Polarizing Tumor-Associated Macrophages.","authors":"Nie, Ying; Shi, Lu; Zhang, Yanan; Guo, Yunfei; Gu, Hongchen","year":2022,"journal":"Cancers, 14(20)","doi":"10.3390/cancers14205107","pmid":"36291890","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The dual-modified nanoparticles achieved a 40% cure rate in a TC1 tumor model.","whyItMatters":"This research could lead to more effective cancer vaccines by overcoming the challenges posed by the tumor microenvironment. Enhancing immune responses against tumors is crucial for improving cancer treatment outcomes.","specificNumbers":"","methodology":"The study involved in vitro and in vivo experiments using modified iron oxide nanoparticles to assess their effects on tumor-associated macrophages and immune cell activation.","limitations":"The study was conducted in mice, and results may not directly translate to humans. Further research is needed to evaluate safety and efficacy in human trials."},{"rthcId":"RPEP-06397","title":"Heterologous Expression and Functional Characterization of CAP18 from Oryctolagus cuniculus.","authors":"Nikpoor, Mahla; Lohrasbi-Nejad, Azadeh; Zolala, Jafar","year":2022,"journal":"Reports of biochemistry & molecular biology, 10(4), 622-632","doi":"10.52547/rbmb.10.4.622","pmid":"35291606","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"rCAP18 reduced bacterial growth by 28% against Pseudomonas aeruginosa at 7 μg/ml concentration.","whyItMatters":"Antimicrobial resistance is a growing concern, and peptides like rCAP18 could provide new options for treatment. Understanding how these peptides work can lead to better therapeutic strategies.","specificNumbers":"","methodology":"The cap18 gene was cloned into a plasmid and expressed in Pichia pastoris, followed by purification and antibacterial testing.","limitations":"The study was conducted in vitro, and results may not directly translate to clinical applications in humans."},{"rthcId":"RPEP-06398","title":"Anamorelin for cancer cachexia.","authors":"Nishie, Kenichi; Sato, Seiichi; Hanaoka, Masayuki","year":2022,"journal":"Drugs of today (Barcelona, Spain : 1998), 58(3), 97-104","doi":"10.1358/dot.2022.58.3.3381585","pmid":"35274629","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Anamorelin led to a significant increase in lean body mass index in clinical trials.","whyItMatters":"This research highlights a potential treatment option for cancer cachexia, improving patients' quality of life. Understanding its effects can help manage weight loss in cancer patients more effectively.","specificNumbers":"","methodology":"The study is a review of clinical trials and pharmacological data on anamorelin.","limitations":"The review may not cover all clinical trials or long-term effects of anamorelin."},{"rthcId":"RPEP-06399","title":"B-Type Natriuretic Peptide (BNP) Revisited-Is BNP Still a Biomarker for Heart Failure in the Angiotensin Receptor/Neprilysin Inhibitor Era?","authors":"Nishikimi, Toshio; Nakagawa, Yasuaki","year":2022,"journal":"Biology, 11(7)","doi":"10.3390/biology11071034","pmid":"36101415","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BNP can still be used for heart failure assessment, despite early increases during ARNI treatment.","whyItMatters":"Understanding BNP's role in heart failure is crucial for effective diagnosis and treatment. This study helps clarify how new therapies impact BNP levels.","specificNumbers":"","methodology":"The study reviews the mechanisms of BNP production and clearance, along with the effects of ARNI on BNP levels.","limitations":"The study is primarily a review and does not present new experimental data."},{"rthcId":"RPEP-06400","title":"Semaglutide is effective in type 2 diabetes and obesity with schizophrenia.","authors":"Noda, Kaoru; Kato, Takehiro; Nomura, Nao; Sakai, Mayu; Kubota, Sodai; Hirose, Tokuyuki; Liu, Yanyan; Takahashi, Yoshihiro; Takao, Ken; Mizuno, Masami; Hirota, Takuo; Suwa, Tetsuya; Horikawa, Yukio; Yabe, Daisuke","year":2022,"journal":"Diabetology international, 13(4), 693-697","doi":"10.1007/s13340-022-00590-1","pmid":"36117924","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A 50-year-old woman with type 2 diabetes, obesity, and schizophrenia had poorly controlled HbA1c (8.0-10.2%) on multiple diabetes medications including dulaglutide, with repeated hospitalizations for suicide attempts via drug overdose. Switching to semaglutide 0.5 mg with multidisciplinary support (including cognitive-behavioral therapy) resulted in: patient-reported hunger suppression, sustained HbA1c improvement, and sustained body weight reduction maintained for 6 months. Semaglutide was remarkably more effective than dulaglutide in this case.","whyItMatters":"People with schizophrenia have 2-3x higher rates of diabetes and obesity, largely driven by antipsychotic medications. They are often excluded from clinical trials and underserved in metabolic care. Demonstrating that semaglutide can effectively control appetite, weight, and blood sugar in this population — where other GLP-1 drugs failed — is clinically significant for the millions of people living with serious mental illness and metabolic comorbidities.","specificNumbers":"","methodology":"Single-patient case report documenting the switch from dulaglutide to semaglutide in the context of inpatient hospitalization with a multidisciplinary team approach including cognitive-behavioral therapy. Outcomes tracked over 6 months post-initiation.","limitations":"This is a single case report — the lowest level of clinical evidence. The improvement cannot be attributed solely to semaglutide, as the multidisciplinary team approach (including CBT) was initiated simultaneously. The 6-month follow-up is relatively short. The patient's psychiatric stability during this period is not detailed. The suicide attempt history raises safety considerations about prescribing injectable medications in this population."},{"rthcId":"RPEP-06401","title":"Real-world evidence following a mandatory treatment break after a 1-year prophylactic treatment with calcitonin gene-related peptide (pathway) monoclonal antibodies.","authors":"Nsaka, Michael; Scheffler, Armin; Wurthmann, Sebastian; Schenk, Hannah; Kleinschnitz, Christoph; Glas, Martin; Holle, Dagny","year":2022,"journal":"Brain and behavior, 12(7), e2662","doi":"10.1002/brb3.2662","pmid":"35687795","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Migraine days increased by 5.18 for episodic and 5.06 for chronic patients during the break.","whyItMatters":"Understanding the impact of treatment breaks can help optimize migraine management strategies. This study highlights the potential negative effects of such breaks on patient well-being.","specificNumbers":"","methodology":"The study analyzed clinical data from 46 migraine patients before treatment, after 12 months of treatment, and during a treatment break.","limitations":"The study's sample size was relatively small, and it focused on a specific patient population, which may limit generalizability."},{"rthcId":"RPEP-06402","title":"Cholecystokinin/sulfakinin peptide signaling: conserved roles at the intersection between feeding, mating and aggression.","authors":"Nässel, Dick R; Wu, Shun-Fan","year":2022,"journal":"Cellular and molecular life sciences : CMLS, 79(3), 188","doi":"10.1007/s00018-022-04214-4","pmid":"35286508","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CCK in mammals and sulfakinins (SKs) in invertebrates share deeply conserved functional roles that extend far beyond gut signaling. In mammals, CCK is produced by both gut endocrine cells and brain neurons and regulates gallbladder contraction, pancreatic enzyme secretion, satiety, reward, anxiety, aggression, and sexual behavior.\n\nIn Drosophila, a set of just eight SK-expressing brain neurons integrates internal state and external stimuli to coordinate competing behavioral outputs: they diminish sugar gustation, induce satiety, reduce feeding, suppress sex drive in males, and increase aggression. This demonstrates that a single neuropeptide system can arbitrate between multiple survival-critical behaviors depending on context. While the functional roles appear conserved between flies and mammals, the underlying neural mechanisms differ.","whyItMatters":"Understanding that a single peptide system coordinates multiple critical behaviors — eating, fighting, and mating — has profound implications for drug development. CCK receptor agonists developed for appetite suppression might unexpectedly affect aggression or sexual behavior, and vice versa. The fly model, with its genetically accessible eight-neuron circuit, provides a powerful tool for dissecting how peptide signaling balances competing drives — insights that could inform more targeted therapies for eating disorders, aggression, and behavioral dysregulation.","specificNumbers":"","methodology":"This is a comprehensive comparative review synthesizing research across invertebrate (primarily Drosophila) and vertebrate (mammalian) systems on CCK/sulfakinin peptide signaling. It draws on genetic manipulation studies in Drosophila, neuroanatomical mapping, behavioral assays, and mammalian pharmacological and neuroimaging studies.","limitations":"The review draws heavily on Drosophila genetics, which may not directly translate to mammalian neurobiology despite functional conservation. The eight-neuron SK circuit in flies has no direct mammalian equivalent — CCK signaling in mammalian brains involves numerous distributed circuits. The complexity of human CCK biology (multiple receptor subtypes, gut vs. brain production, interaction with other neurotransmitter systems) is not fully captured by the fly model. Clinical implications for human behavioral disorders remain speculative."},{"rthcId":"RPEP-06403","title":"Exploring the wider benefits of semaglutide treatment in obesity: insight from the STEP program.","authors":"O'Neil, Patrick M; Rubino, Domenica M","year":2022,"journal":"Postgraduate medicine, 134(sup1), 28-36","doi":"10.1080/00325481.2022.2150006","pmid":"36691307","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide 2.4 mg significantly improved quality of life scores and reduced total fat mass compared to placebo.","whyItMatters":"Understanding the broader benefits of semaglutide can help healthcare providers make informed decisions about obesity treatment options, improving patient outcomes.","specificNumbers":"","methodology":"The study analyzed data from the STEP trials, comparing semaglutide 2.4 mg with placebo in adults with obesity, assessing quality of life and body composition.","limitations":"The study primarily focuses on specific subgroups and may not represent all patients with obesity."},{"rthcId":"RPEP-06404","title":"Antimicrobial production by perifollicular dermal preadipocytes is essential to the pathophysiology of acne.","authors":"O'Neill, Alan M; Liggins, Marc C; Seidman, Jason S; Do, Tran H; Li, Fengwu; Cavagnero, Kellen J; Dokoshi, Tatsuya; Cheng, Joyce Y; Shafiq, Faiza; Hata, Tissa R; Gudjonsson, Johann E; Modlin, Robert L; Gallo, Richard L","year":2022,"journal":"Science translational medicine, 14(632), eabh1478","doi":"10.1126/scitranslmed.abh1478","pmid":"35171653","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Retinoic acid treatment increased cathelicidin expression in preadipocytes, enhancing antimicrobial defense.","whyItMatters":"Understanding the role of skin cells in acne could lead to new treatments that enhance the skin's natural defenses. This research opens up potential therapeutic avenues for managing acne more effectively.","specificNumbers":"","methodology":"The study utilized single-cell RNA sequencing on human acne lesions and mouse skin infected with C. acnes to analyze gene expression.","limitations":"The study primarily focuses on mouse models and human skin samples, which may not fully represent all acne cases or responses in the general population."},{"rthcId":"RPEP-06405","title":"Antitumor efficacy of MUC1-derived variable epitope library treatments in a mouse model of breast cancer.","authors":"Odales, Josué; Servín-Blanco, Rodolfo; Martínez-Cortés, Fernando; Guzman Valle, Jesus; Domínguez-Romero, Allan Noé; Gevorkian, Goar; Manoutcharian, Karen","year":2022,"journal":"Vaccine, 40(33), 4796-4805","doi":"10.1016/j.vaccine.2022.06.062","pmid":"35788294","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Vaccination with the 23L VEL reduced tumor area compared to wild-type treatment, while 9MUC1spL decreased lung metastasis.","whyItMatters":"These findings could lead to more effective immunotherapies for breast cancer, particularly for patients with MUC1 overexpression. Enhancing immune responses against tumors is crucial for improving cancer treatment outcomes.","specificNumbers":"","methodology":"The study used a mouse model to test the efficacy of MUC1-derived VELs in reducing tumor size and metastasis.","limitations":"The study was conducted in a mouse model, which may not fully replicate human responses. Further research is needed to confirm these findings in clinical trials."},{"rthcId":"RPEP-06406","title":"Headache: Treatment update.","authors":"Ogunlaja, Oyindamola I; Goadsby, Peter J","year":2022,"journal":"eNeurologicalSci, 29, 100420","doi":"10.1016/j.ensci.2022.100420","pmid":"36636337","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"New migraine treatments include lasmiditan and CGRP antagonists, but cost limits access.","whyItMatters":"Understanding new treatment options is crucial for managing migraine, a leading cause of disability. Improved therapies can enhance the quality of life for many patients.","specificNumbers":"","methodology":"The study is a review of recent literature on migraine treatments and their effectiveness.","limitations":"The review does not include clinical trial data or patient outcomes for the new treatments."},{"rthcId":"RPEP-06407","title":"Blockade of TMPRSS2-mediated priming of SARS-CoV-2 by lactoferricin.","authors":"Ohradanova-Repic, Anna; Skrabana, Rostislav; Gebetsberger, Laura; Tajti, Gabor; Baráth, Peter; Ondrovičová, Gabriela; Praženicová, Romana; Jantova, Nikola; Hrasnova, Patricia; Stockinger, Hannes; Leksa, Vladimir","year":2022,"journal":"Frontiers in immunology, 13, 958581","doi":"10.3389/fimmu.2022.958581","pmid":"36081512","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Lactoferricin and pLF1 inhibited TMPRSS2 activity and SARS-CoV-2 infection.","whyItMatters":"As COVID-19 continues to pose a global health threat, finding effective antiviral therapies is crucial. This research highlights potential new treatments that could complement existing vaccines.","specificNumbers":"","methodology":"The study tested lactoferricin and synthetic peptides for their ability to block TMPRSS2 and SARS-CoV-2 infection in laboratory conditions.","limitations":"The study was conducted in vitro, so results may not directly translate to clinical effectiveness in humans."},{"rthcId":"RPEP-06408","title":"Pigeon pea penta- and hexapeptides with antioxidant properties also inhibit renin and angiotensin-I-converting enzyme activities.","authors":"Olagunju, Aderonke I; Alashi, Adeola M; Omoba, Olufunmilayo S; Enujiugha, Victor N; Aluko, Rotimi E","year":2022,"journal":"Journal of food biochemistry, 46(12), e14485","doi":"10.1111/jfbc.14485","pmid":"36250929","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Peptides inhibited ACE activity by 7.4-100% and scavenged radicals by 31.9-100%.","whyItMatters":"The study highlights the potential of pigeon pea peptides as functional ingredients in food, which could help manage health issues like hypertension. This research adds to the understanding of plant-based proteins and their bioactive properties.","specificNumbers":"","methodology":"Pigeon pea protein was digested with pepsin and pancreatin, followed by fractionation using HPLC and analysis of antioxidant and enzyme inhibition activities.","limitations":"The study was conducted in vitro, so results may not directly translate to human health outcomes."},{"rthcId":"RPEP-06409","title":"Peptide-Based Supramolecular Hydrogels as Drug Delivery Agents: Recent Advances.","authors":"Oliveira, Carlos B P; Gomes, Valéria; Ferreira, Paula M T; Martins, José A; Jervis, Peter J","year":2022,"journal":"Gels (Basel, Switzerland), 8(11)","doi":"10.3390/gels8110706","pmid":"36354614","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review highlights that peptide-based supramolecular hydrogels have made significant advances in drug delivery through several key developments: improved peptide self-assembly techniques that create more stable gel structures, functionalization strategies that enable targeted delivery, bioadhesive properties that keep gels in place at treatment sites, and enhanced drug release profiles that can be tuned for sustained or triggered release.\n\nParticularly notable progress has been made in anticancer drug loading and release, where different hydrogel matrix designs allow controlled delivery of chemotherapy agents directly to tumor sites, potentially reducing the systemic toxicity associated with conventional chemotherapy.","whyItMatters":"Systemic drug delivery — where a drug circulates throughout the entire body — causes side effects from off-target binding. Peptide hydrogels enable localized, sustained drug release at the treatment site, which could transform how diseases like cancer are treated by delivering effective doses where they're needed while minimizing toxicity elsewhere.","specificNumbers":"","methodology":"This is a comprehensive literature review covering discoveries in peptide-based supramolecular hydrogels for drug delivery reported primarily between 2018 and 2022. The authors survey advances in self-assembly, mechanical properties, functionalization, bioadhesion, drug release profiles, and anticancer drug delivery applications.","limitations":"As a review, this paper synthesizes existing literature rather than presenting new experimental data. Many of the advances described are at the preclinical stage, and the translation of peptide hydrogels from laboratory to clinical use faces challenges including scalability, regulatory approval, and long-term stability in biological environments."},{"rthcId":"RPEP-06410","title":"Compartmentalized Innate Immune Response of Human Fetal Membranes against Escherichia coli Choriodecidual Infection.","authors":"Olmos-Ortiz, Andrea; Hernández-Pérez, Mayra; Flores-Espinosa, Pilar; Sedano, Gabriela; Helguera-Repetto, Addy Cecilia; Villavicencio-Carrisoza, Óscar; Valdespino-Vazquez, María Yolotzin; Flores-Pliego, Arturo; Irles, Claudine; Rivas-Santiago, Bruno; Moreno-Verduzco, Elsa Romelia; Díaz, Lorenza; Zaga-Clavellina, Verónica","year":2022,"journal":"International journal of molecular sciences, 23(6)","doi":"10.3390/ijms23062994","pmid":"35328414","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"E. coli infection led to mechanical disruption of membranes and increased AMP production, but membranes couldn't prevent bacterial growth.","whyItMatters":"Understanding how fetal membranes respond to infections is crucial for developing strategies to prevent complications like preterm birth. This research highlights the limitations of the immune response in fetal membranes.","specificNumbers":"","methodology":"The study used a two-compartment model with human chorioamniotic membranes infected with live E. coli to measure AMP levels and inflammatory markers.","limitations":"The study is limited to in vitro findings, which may not fully translate to in vivo conditions in humans."},{"rthcId":"RPEP-06411","title":"Development of a Personalized Tumor Neoantigen Based Vaccine Formulation (FRAME-001) for Use in a Phase II Trial for the Treatment of Advanced Non-Small Cell Lung Cancer.","authors":"Oosting, Linette T; Franke, Katka; Martin, Michael V; Kloosterman, Wigard P; Jamieson, Jennifer A; Glenn, Laura A; de Jager, Miranda W; van Zanten, Jacoba; Allersma, Derk P; Gareb, Bahez","year":2022,"journal":"Pharmaceutics, 14(7)","doi":"10.3390/pharmaceutics14071515","pmid":"35890409","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"FRAME-001 is a stable personalized vaccine formulation for advanced NSCLC, stable for up to 32 weeks.","whyItMatters":"This research could lead to more effective personalized therapies for lung cancer, potentially improving patient outcomes. It also sets a precedent for developing similar vaccines for other cancers.","specificNumbers":"","methodology":"The study involved synthesizing neoantigen peptides and formulating them into a vaccine under good manufacturing practices, followed by stability testing.","limitations":"The study primarily focuses on formulation and stability, with clinical efficacy yet to be established in trials."},{"rthcId":"RPEP-06412","title":"Borrelia burgdorferi is strong inducer of IFN-γ production by human primary NK cells.","authors":"Oosting, Marije; Brouwer, Michelle; Vrijmoeth, Hedwig D; Pascual Domingo, Rosa; Greco, Anna; Ter Hofstede, Hadewych; van den Bogaard, Ellen H; Schalkwijk, Joost; Netea, Mihai G; Joosten, Leo A B","year":2022,"journal":"Cytokine, 155, 155895","doi":"10.1016/j.cyto.2022.155895","pmid":"35569383","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CD56+ NK cells produced IFN-γ within 24 hours of exposure to B. burgdorferi.","whyItMatters":"Understanding how NK cells respond to Borrelia burgdorferi can help in developing better treatments for Lyme disease and improving immune response strategies.","specificNumbers":"","methodology":"The study assessed cytokine production by human primary peripheral blood mononuclear cells exposed to Borrelia burgdorferi.","limitations":"The study primarily focuses on in vitro responses, which may not fully represent in vivo conditions."},{"rthcId":"RPEP-06413","title":"Effect of antibody switch in non-responders to a CGRP receptor antibody treatment in migraine: A multi-center retrospective cohort study.","authors":"Overeem, Lucas Hendrik; Peikert, Andreas; Hofacker, Maxi Dana; Kamm, Katharina; Ruscheweyh, Ruth; Gendolla, Astrid; Raffaelli, Bianca; Reuter, Uwe; Neeb, Lars","year":2022,"journal":"Cephalalgia : an international journal of headache, 42(4-5), 291-301","doi":"10.1177/03331024211048765","pmid":"34644203","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"32% of patients had a ≥30% reduction in headache days after switching treatments.","whyItMatters":"This research suggests that switching treatments could provide relief for some migraine patients who do not respond to their initial therapy, potentially improving their quality of life.","specificNumbers":"","methodology":"The study analyzed retrospective headache diary data from 78 migraine patients who switched CGRP monoclonal antibodies.","limitations":"The study is retrospective and has a small sample size, which may limit the generalizability of the findings."},{"rthcId":"RPEP-06414","title":"Cooperative Metal Ion Coordination to the Short Self-Assembling Peptide Promotes Hydrogelation and Cellular Proliferation.","authors":"Pal, Vijay Kumar; Roy, Sangita","year":2022,"journal":"Macromolecular bioscience, 22(5), e2100462","doi":"10.1002/mabi.202100462","pmid":"35257490","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Metal ions significantly improved gelation and cellular response in peptide hydrogels.","whyItMatters":"This research could lead to the development of advanced biomaterials that are more effective in medical applications, particularly in tissue engineering.","specificNumbers":"","methodology":"The study involved microscopic analyses, rheological assessments, and biological tests to evaluate the effects of metal ions on peptide gelation and cellular behavior.","limitations":"The study primarily focuses on in vitro conditions, which may not fully replicate in vivo environments."},{"rthcId":"RPEP-06415","title":"Truncated Lactoferricin Peptide Controls Cervical Cancer Cell Proliferation via lncRNA-NKILA/NF-κB Feedback Loop.","authors":"Pan, Yuan; Jiang, Yuting; Cui, Yingli; Zhu, Jihong; Yu, Yang","year":2022,"journal":"Protein and peptide letters, 29(3), 268-280","doi":"10.2174/0929866528666211206144110","pmid":"34872471","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"TLP18 inhibited cervical cancer cell growth up to 0.4-fold more than LP, with significant changes in NKILA and NF-κB levels.","whyItMatters":"Understanding how TLP18 works could lead to new therapeutic strategies for cervical cancer, a significant health concern worldwide.","specificNumbers":"","methodology":"The study used bioinformatics analysis and experimental treatments on cervical cancer cell lines (SiHa and HeLa) to assess the effects of TLP18 and LP.","limitations":"The study was conducted in vitro, and results may not directly translate to human patients."},{"rthcId":"RPEP-06416","title":"The anti-inflammatory feature of glucagon-like peptide-1 and its based diabetes drugs-Therapeutic potential exploration in lung injury.","authors":"Pang, Juan; Feng, Jia Nuo; Ling, Wenhua; Jin, Tianru","year":2022,"journal":"Acta pharmaceutica Sinica. B, 12(11), 4040-4055","doi":"10.1016/j.apsb.2022.06.003","pmid":"36386481","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1RAs exhibit promising anti-inflammatory effects in lung injury models.","whyItMatters":"Understanding the anti-inflammatory effects of GLP-1RAs could lead to new treatments for lung diseases. This research may broaden the therapeutic applications of diabetes medications.","specificNumbers":"","methodology":"The study is a literature review summarizing findings from various animal studies on GLP-1RAs and lung inflammation.","limitations":"The review primarily discusses animal studies, which may not directly translate to human outcomes."},{"rthcId":"RPEP-06417","title":"Human β-Defensin-3 is Associated With Platelet-Derived Extracellular Vesicles and is a Potential Contributor to Endothelial Dysfunction.","authors":"Panigrahi, Soumya; Ghosh, Santosh K; Ferrari, Brian; Wyrick, Jonathan M; Podrez, Eugene A; Weinberg, Aaron; Sieg, Scott F","year":2022,"journal":"Frontiers in molecular biosciences, 9, 824954","doi":"10.3389/fmolb.2022.824954","pmid":"35355507","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"hBD-3 in platelet-derived extracellular vesicles caused significant endothelial dysfunction.","whyItMatters":"Understanding the role of hBD-3 in platelet function could reveal new insights into vascular health and disease mechanisms. It highlights a potential link between immunity and blood clotting.","specificNumbers":"","methodology":"The study utilized immunofluorescent microscopy, western blot, ELISA, flow cytometry, and immuno-electron microscopy to analyze hBD-3 in platelets and its effects on endothelial cells.","limitations":"The study was conducted in vitro, which may limit the applicability of findings to living organisms."},{"rthcId":"RPEP-06418","title":"GLP-1 receptor agonists, polycystic ovary syndrome and reproductive dysfunction: Current research and future horizons.","authors":"Papaetis, Georgios S; Kyriacou, Angelos","year":2022,"journal":"Advances in clinical and experimental medicine : official organ Wroclaw Medical University, 31(11), 1265-1274","doi":"10.17219/acem/151695","pmid":"35951627","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1R agonists may improve ovarian morphology and menstrual function in women with PCOS.","whyItMatters":"Understanding the role of GLP-1R agonists in PCOS could lead to better treatments for women facing reproductive challenges. This could improve fertility outcomes and overall health.","specificNumbers":"","methodology":"This is a review study analyzing existing research on GLP-1 receptor agonists and their effects on PCOS.","limitations":"As a review, it synthesizes existing studies but does not present new experimental data. The variability in study designs and populations may affect conclusions."},{"rthcId":"RPEP-06419","title":"RpoN-Based stapled peptides with improved DNA binding suppress Pseudomonas aeruginosa virulence.","authors":"Paquette, André R; Payne, Sterling R; McKay, Geoffrey A; Brazeau-Henrie, Jordan T; Darnowski, Micheal G; Kammili, Anitha; Bernal, Federico; Mah, Thien-Fah; Gruenheid, Samantha; Nguyen, Dao; Boddy, Christopher N","year":2022,"journal":"RSC medicinal chemistry, 13(4), 445-455","doi":"10.1039/d1md00371b","pmid":"35647551","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Lead peptides showed low toxicity and anti-virulence activity against Pseudomonas aeruginosa.","whyItMatters":"These findings highlight a promising approach to combat bacterial infections, particularly those caused by antibiotic-resistant strains. The use of stapled peptides could lead to new treatments that specifically target bacterial virulence.","specificNumbers":"","methodology":"The study involved developing stapled peptides, assessing their DNA binding affinity, and testing their effects in a Galleria mellonella infection model.","limitations":"The study primarily used a model organism (Galleria mellonella), which may not fully replicate human responses."},{"rthcId":"RPEP-06420","title":"Multifunctional synthetic nano-chaperone for peptide folding and intracellular delivery.","authors":"Park, Il-Soo; Kim, Seongchan; Yim, Yeajee; Park, Ginam; Choi, Jinahn; Won, Cheolhee; Min, Dal-Hee","year":2022,"journal":"Nature communications, 13(1), 4568","doi":"10.1038/s41467-022-32268-2","pmid":"35931667","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The synthetic nano-chaperone improved cellular uptake and bioavailability of peptides, effectively inhibiting cancer growth.","whyItMatters":"This research could lead to more effective peptide therapies for cancer by addressing the challenges of peptide stability and delivery.","specificNumbers":"","methodology":"The study involved creating porous nanoparticles that stabilize α-helical peptides and testing their delivery and efficacy in cancer cells.","limitations":"The study primarily focuses on in vitro and in vivo models, which may not fully predict human responses."},{"rthcId":"RPEP-06421","title":"In Silico Design and In Vitro Evaluation of Some Novel AMPs Derived From Human LL-37 as Potential Antimicrobial Agents for Keratitis.","authors":"Pashapour, Arsalan; Sardari, Soroush; Ehsani, Parastoo","year":2022,"journal":"Iranian journal of pharmaceutical research : IJPR, 21(1), e124017","doi":"10.5812/ijpr-124017","pmid":"36710989","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Catoid showed superior antimicrobial activity against P. aeruginosa and lower toxicity than LL-37.","whyItMatters":"These findings could lead to new treatments for bacterial keratitis, potentially reducing reliance on traditional antibiotics. The low toxicity of these peptides also suggests they may be safer for human use.","specificNumbers":"","methodology":"The study involved designing peptides using bioinformatics, synthesizing them, and testing their antimicrobial activity and cytotoxicity in vitro.","limitations":"The study was conducted in vitro, so results may not directly translate to clinical effectiveness in humans."},{"rthcId":"RPEP-06422","title":"Design, synthesis and preclinical evaluation of bio-conjugated amylinomimetic peptides as long-acting amylin receptor agonists.","authors":"Patch, Raymond J; Zhang, Rui; Edavettal, Suzanne; Macielag, Mark J; Eckardt, Annette J; Li, Jiali; Rives, Marie-Laure; Edwards, Wilson; Hinke, Simon A; Qiu, Xi; Jian, Wenying; Libiger, Ondrej; Zheng, Songmao; Jeyaseelan, Jey; Liang, Yin; Rangwala, Shamina M; Leonard, James N; Hornby, Pamela","year":2022,"journal":"European journal of medicinal chemistry, 236, 114330","doi":"10.1016/j.ejmech.2022.114330","pmid":"35436670","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Bioconjugates 35 and 38 have terminal half-lives of ∼2 days in mice, compared to pramlintide's half-life of <0.75 h.","whyItMatters":"These long-acting peptides could reduce the need for multiple daily doses, making obesity treatment more manageable. They also provide insights into developing new therapies for obesity-related conditions.","specificNumbers":"","methodology":"The study involved the design and synthesis of peptide bioconjugates, followed by in vivo testing in mice to evaluate their pharmacokinetics and effects on food intake.","limitations":"The study was conducted in mice, and results may not directly translate to humans. Further clinical trials are needed."},{"rthcId":"RPEP-06423","title":"Monoclonal Antibodies against Calcitonin Gene-Related Peptide for Migraine Prophylaxis: A Systematic Review of Real-World Data.","authors":"Pavelic, Antun R; Wöber, Christian; Riederer, Franz; Zebenholzer, Karin","year":2022,"journal":"Cells, 12(1)","doi":"10.3390/cells12010143","pmid":"36611935","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Anti-CGRP monoclonal antibodies showed effectiveness comparable to randomized trials, with improved treatment adherence.","whyItMatters":"Understanding the effectiveness of anti-CGRP monoclonal antibodies in real-world settings can help improve migraine management. This research highlights the need for larger studies to confirm these findings.","specificNumbers":"","methodology":"The study conducted a systematic review following PRISMA guidelines, analyzing real-world data from 134 publications.","limitations":"The review is limited by the retrospective nature of many studies, small sample sizes, and short follow-up durations."},{"rthcId":"RPEP-06424","title":"Oral lactate slows gastric emptying and suppresses appetite in young males.","authors":"Pedersen, Mette Glavind Bülow; Søndergaard, Esben; Nielsen, Camilla Bak; Johannsen, Mogens; Gormsen, Lars Christian; Møller, Niels; Jessen, Niels; Rittig, Nikolaj","year":2022,"journal":"Clinical nutrition (Edinburgh, Scotland), 41(2), 517-525","doi":"10.1016/j.clnu.2021.12.032","pmid":"35016146","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Oral lactate slowed gastric emptying (p < 0.001) and increased feelings of fullness (p = 0.008).","whyItMatters":"Understanding how lactate influences appetite could lead to new treatments for metabolic diseases. This research highlights the potential of dietary compounds in managing appetite and digestion.","specificNumbers":"","methodology":"The study involved ten male participants who ingested either oral lactate or a saline solution on separate occasions, with appetite and gastric emptying assessed through questionnaires and tests.","limitations":"The study was limited to a small sample size of ten healthy males, which may not represent broader populations."},{"rthcId":"RPEP-06425","title":"GLP-1 Agonist to Treat Obesity and Prevent Cardiovascular Disease: What Have We Achieved so Far?","authors":"Pedrosa, Maurício Reis; Franco, Denise Reis; Gieremek, Hannah Waisberg; Vidal, Camila Maia; Bronzeri, Fernanda; de Cassia Rocha, Alexia; de Carvalho Cara, Luis Gabriel; Fogo, Sofia Lenzi; Eliaschewitz, Freddy Goldberg","year":2022,"journal":"Current atherosclerosis reports, 24(11), 867-884","doi":"10.1007/s11883-022-01062-2","pmid":"36044100","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1RAs significantly decrease cardiovascular risk in obese patients with type 2 diabetes.","whyItMatters":"Understanding the benefits of GLP-1RAs can help in developing effective obesity treatments that also lower heart disease risk. This could lead to improved health outcomes for many patients.","specificNumbers":"","methodology":"The study is a review of existing clinical trials and evidence regarding GLP-1RAs for obesity and cardiovascular protection.","limitations":"The review relies on existing studies, which may vary in design and outcomes, and some results are still pending."},{"rthcId":"RPEP-06426","title":"Designing Cell-Permeable Peptide Therapeutics That Enter the Cell by Endocytosis.","authors":"Pei, Dehua","year":2022,"journal":"ACS symposium series. American Chemical Society, 1417, 179-197","doi":"10.1021/bk-2022-1417.ch007","pmid":"37621949","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Cyclic cell-penetrating peptides can deliver therapeutic peptides into cells effectively.","whyItMatters":"This research is significant because it addresses a major challenge in drug development: delivering therapeutics inside cells. Improved peptide delivery could lead to new treatments for diseases that involve protein interactions.","specificNumbers":"","methodology":"The study reviews strategies for conjugating different peptide types with cyclic cell-penetrating peptides.","limitations":"The study primarily focuses on theoretical strategies and may require further experimental validation."},{"rthcId":"RPEP-06427","title":"How Do Biomolecules Cross the Cell Membrane?","authors":"Pei, Dehua","year":2022,"journal":"Accounts of chemical research, 55(3), 309-318","doi":"10.1021/acs.accounts.1c00560","pmid":"35015508","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The study identifies the vesicle budding-and-collapse (VBC) mechanism as a way for biomolecules to translocate across membranes.","whyItMatters":"Understanding how biomolecules cross cell membranes is crucial for developing more effective drug delivery systems. This new mechanism could lead to advancements in treatments for various diseases.","specificNumbers":"","methodology":"The researchers used confocal microscopy to track biomolecule movement in real time, labeling them with specific dyes to observe their behavior in giant unilamellar vesicles and live mammalian cells.","limitations":"The study primarily focuses on specific biomolecules and may not fully represent all types of molecules or conditions in living organisms."},{"rthcId":"RPEP-06428","title":"Designer self-assembling peptide nanofibers induce biomineralization of lidocaine for slow-release and prolonged analgesia.","authors":"Peng, Fei; Liu, Jing; Zhang, Yujun; Fan, Jing; Gong, Deying; He, Liu; Zhang, Wensheng; Qiu, Feng","year":2022,"journal":"Acta biomaterialia, 146, 66-79","doi":"10.1016/j.actbio.2022.05.002","pmid":"35545185","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06429","title":"Novel Therapeutic Effects in Rat Spinal Cord Injuries: Recovery of the Definitive and Early Spinal Cord Injury by the Administration of Pentadecapeptide BPC 157 Therapy.","authors":"Perovic, Darko; Milavic, Marija; Dokuzovic, Stjepan; Krezic, Ivan; Gojkovic, Slaven; Vranes, Hrvoje; Bebek, Igor; Bilic, Vide; Somun, Nenad; Brizic, Ivan; Skorak, Ivan; Hriberski, Klaudija; Sikiric, Suncana; Lovric, Eva; Strbe, Sanja; Kubat, Milovan; Boban Blagaic, Alenka; Skrtic, Anita; Seiwerth, Sven; Sikiric, Predrag","year":2022,"journal":"Current issues in molecular biology, 44(5), 1901-1927","doi":"10.3390/cimb44050130","pmid":"35678659","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06430","title":"Endogenous Opioids and Their Role in Stem Cell Biology and Tissue Rescue.","authors":"Petrocelli, Giovannamaria; Pampanella, Luca; Abruzzo, Provvidenza M; Ventura, Carlo; Canaider, Silvia; Facchin, Federica","year":2022,"journal":"International journal of molecular sciences, 23(7)","doi":"10.3390/ijms23073819","pmid":"35409178","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Endogenous opioids modulate stem cell proliferation and differentiation.","whyItMatters":"Understanding how opioids influence stem cells could lead to improved therapies for tissue repair and regeneration. This knowledge is crucial for developing effective regenerative medicine strategies.","specificNumbers":"","methodology":"The study reviews existing literature on the role of endogenous opioids in stem cell biology.","limitations":"The study is primarily a literature review and does not present new experimental data."},{"rthcId":"RPEP-06431","title":"The neurobiology of bremelanotide for the treatment of hypoactive sexual desire disorder in premenopausal women.","authors":"Pfaus, James G; Sadiq, Amama; Spana, Carl; Clayton, Anita H","year":2022,"journal":"CNS spectrums, 27(3), 281-289","doi":"10.1017/S109285292100002X","pmid":"33455598","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Bremelanotide activates melanocortin receptors, particularly MC4R, to potentially increase dopamine release.","whyItMatters":"Understanding how bremelanotide works can improve treatment options for women suffering from HSDD. This could lead to better management of female sexual dysfunction.","specificNumbers":"","methodology":"This is a review study summarizing existing research on bremelanotide's mechanism of action.","limitations":"As a review, it summarizes existing studies but does not present new experimental data."},{"rthcId":"RPEP-06432","title":"Characterization of growth hormone secretagogue small molecule ibutamoren (MK-0677) and its possible metabolites in thoroughbred horses for doping control.","authors":"Philip, Moses; Karakka Kal, Abdul Khader; Subhahar, Michael Benedict; Karatt, Tajudheen K; Mathew, Binoy; Koshy, Shino Ann","year":2022,"journal":"Rapid communications in mass spectrometry : RCM, 36(18), e9337","doi":"10.1002/rcm.9337","pmid":"35716382","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"22 metabolites of ibutamoren were identified, detectable for up to 96 hours.","whyItMatters":"Understanding how ibutamoren metabolizes helps improve doping control in competitive sports. This knowledge can help ensure fair competition by identifying illegal substance use.","specificNumbers":"","methodology":"The study used liquid chromatography and high-resolution mass spectrometry to analyze ibutamoren and its metabolites in thoroughbred horses after oral administration.","limitations":"The study is limited to thoroughbred horses, and results may not directly apply to other species or humans."},{"rthcId":"RPEP-06433","title":"The Role of Oxytocin in Social Circuits and Social Behavior in Dementia.","authors":"Piguet, Olivier; Ahmed, Rebekah M; Kumfor, Fiona","year":2022,"journal":"Methods in molecular biology (Clifton, N.J.), 2384, 67-80","doi":"10.1007/978-1-0716-1759-5_5","pmid":"34550569","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Intranasal oxytocin may improve social cognition deficits in frontotemporal dementia.","whyItMatters":"Understanding how oxytocin can aid social cognition in dementia could lead to new treatment options. This is particularly important as social deficits significantly impact quality of life.","specificNumbers":"","methodology":"The chapter reviews existing literature on oxytocin's effects on social cognition in dementia.","limitations":"The chapter primarily reviews existing literature and does not present new experimental data."},{"rthcId":"RPEP-06434","title":"Effects of Tirzepatide, a Dual GIP and GLP-1 RA, on Lipid and Metabolite Profiles in Subjects With Type 2 Diabetes.","authors":"Pirro, Valentina; Roth, Kenneth D; Lin, Yanzhu; Willency, Jill A; Milligan, Paul L; Wilson, Jonathan M; Ruotolo, Giacomo; Haupt, Axel; Newgard, Christopher B; Duffin, Kevin L","year":2022,"journal":"The Journal of clinical endocrinology and metabolism, 107(2), 363-378","doi":"10.1210/clinem/dgab722","pmid":"34608929","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 259 T2D patients over 26 weeks, higher-dose tirzepatide (vs dulaglutide and placebo):\n\n- Reduced branched-chain amino acids (BCAAs) and their catabolic products (glutamate, 3-hydroxyisobutyrate, branched-chain ketoacids)\n- Decreased 2-hydroxybutyrate — a marker of metabolic stress\n- Significantly lowered triglycerides and diglycerides, particularly shorter, highly saturated species\n- Changes were directly proportional to reductions in HbA1c, HOMA2-IR (insulin resistance), and proinsulin levels\n- Improvements were significantly larger with tirzepatide than dulaglutide\n- Effects were only partially attributable to weight loss, suggesting direct metabolic modulation\n- Changes consistent with improved metabolic health and reduced T2D risk markers","whyItMatters":"This study provides molecular evidence that tirzepatide's dual GIP/GLP-1 mechanism produces metabolic improvements that go beyond what single-pathway GLP-1 drugs achieve. The reduction in BCAAs and insulin resistance markers suggests tirzepatide fundamentally remodels metabolic pathways, potentially explaining its superior clinical outcomes for both diabetes and obesity.","specificNumbers":"","methodology":"Post hoc exploratory metabolomics and lipidomics analysis of a Phase 2b randomized trial. 259 subjects with T2D received weekly subcutaneous tirzepatide (1, 5, 10, or 15 mg), dulaglutide (1.5 mg), or placebo for 26 weeks. Plasma metabolite and lipid changes were assessed with multiplicity correction, comparing tirzepatide to baseline, dulaglutide, and placebo.","limitations":"This was a post hoc exploratory analysis, not a pre-specified endpoint, which limits the certainty of conclusions. The 26-week duration may not capture long-term metabolic changes. The dulaglutide comparator dose (1.5 mg) may not be the most equivalent comparison to higher-dose tirzepatide. Metabolomics findings are associative and don't prove causation. The relatively small sample size for metabolomics studies (259 participants) limits statistical power for some comparisons."},{"rthcId":"RPEP-06435","title":"GM-CSF elicits antibodies to tumor-associated proteins when used as a prostate cancer vaccine adjuvant.","authors":"Potluri, Hemanth K; Ng, Tun L; Newton, Michael A; McNeel, Douglas G","year":2022,"journal":"Cancer immunology, immunotherapy : CII, 71(9), 2267-2275","doi":"10.1007/s00262-022-03150-3","pmid":"35133464","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Antibody responses to 5680 peptides were detected only with GM-CSF as an adjuvant.","whyItMatters":"Understanding how GM-CSF influences antibody production can improve vaccine strategies for prostate cancer. This research suggests that antibody responses may not reliably indicate immune spread, prompting a reevaluation of assessment methods.","specificNumbers":"","methodology":"The study evaluated sera from prostate cancer patients in four clinical trials, using a peptide array of 177,604 peptides.","limitations":"The study focuses on antibody responses and does not assess T cell responses directly, which may provide a more accurate measure of immune spread."},{"rthcId":"RPEP-06436","title":"The effects of whey proteins, their peptides and amino acids on vascular function.","authors":"Price, Drew; Jackson, Kim G; Lovegrove, Julie A; Givens, David Ian","year":2022,"journal":"Nutrition bulletin, 47(1), 9-26","doi":"10.1111/nbu.12543","pmid":"36045079","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Whey proteins and their peptides can improve vascular function and lower blood pressure.","whyItMatters":"Understanding the role of dietary proteins like whey in vascular health could lead to effective nutritional strategies for reducing cardiovascular disease risk.","specificNumbers":"","methodology":"The study is a narrative review of evidence from randomized controlled trials and other research methods.","limitations":"The review primarily focuses on existing studies without new experimental data, which may limit the depth of insight."},{"rthcId":"RPEP-06437","title":"Modified Bovine Milk Exosomes for Doxorubicin Delivery to Triple-Negative Breast Cancer Cells.","authors":"Pullan, Jessica; Dailey, Kaitlin; Bhallamudi, Sangeeta; Feng, Li; Alhalhooly, Lina; Froberg, Jamie; Osborn, Jenna; Sarkar, Kausik; Molden, Todd; Sathish, Venkatachalem; Choi, Yongki; Brooks, Amanda; Mallik, Sanku","year":2022,"journal":"ACS applied bio materials, 5(5), 2163-2175","doi":"10.1021/acsabm.2c00015","pmid":"35417133","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Cell viability was reduced by 50% at 10 μM iDHRX in 3D spheroid models using four different triple-negative breast cancer cell lines.","whyItMatters":"This research could lead to more effective drug delivery systems for treating aggressive breast cancer, which currently has limited treatment options.","specificNumbers":"","methodology":"The study involved modifying bovine milk exosomes with a peptide and lipid, followed by in vitro testing on triple-negative breast cancer cells in both monolayer and 3D spheroid cultures.","limitations":"The study was conducted in vitro, and results may not fully translate to in vivo conditions or human patients."},{"rthcId":"RPEP-06438","title":"Determination of the Prevalence of Postcovid Syndrome and Assessment of the Effectiveness of the Drug Cortexin in the Treatment of Neurological Disorders in Patients with Postcovid Syndrome. Results of the CORTEX Multicenter Clinical and Epidemiological Observational Program.","authors":"Putilina, M V; Mutovina, Z Yu; Kurushina, O V; Khalilova, D M; Saverskaya, E N; Stepanova, S B; Khoreva, M A; Starikov, A S","year":2022,"journal":"Neuroscience and behavioral physiology, 52(6), 836-841","doi":"10.1007/s11055-022-01307-2","pmid":"36311877","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06439","title":"Design and characterization of a triazole-based growth hormone secretagogue receptor modulator inhibiting the glucoregulatory and feeding actions of ghrelin.","authors":"Péraldi-Roux, Sylvie; Bayle, Morgane; M'Kadmi, Céline; Damian, Marjorie; Vaillé, Justine; Fernandez, Gimena; Cornejo, Maria Paula; Marie, Jacky; Banères, Jean-Louis; Ben Haj Salah, Khoubaib; Fehrentz, Jean-Alain; Cantel, Sonia; Perello, Mario; Denoyelle, Séverine; Oiry, Catherine; Neasta, Jérémie","year":2022,"journal":"Biochemical pharmacology, 202, 115114","doi":"10.1016/j.bcp.2022.115114","pmid":"35659880","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"JMV 6616 inhibited GHSR activity and blocked ghrelin's effects on blood glucose and appetite in mice.","whyItMatters":"This research could lead to new treatments for obesity and metabolic disorders by targeting ghrelin signaling. It highlights the potential of GHSR modulators in managing these conditions.","specificNumbers":"","methodology":"The study involved in vitro tests on HEK293T cells and in vivo tests in mice to assess the effects of JMV 6616 on GHSR activity.","limitations":"The study primarily used in vitro and animal models, which may not fully translate to human outcomes."},{"rthcId":"RPEP-06440","title":"Frequency-Tagging EEG of Superimposed Social and Non-Social Visual Stimulation Streams Provides No Support for Social Salience Enhancement after Intranasal Oxytocin Administration.","authors":"Qiao, Zhiling; Van der Donck, Stephanie; Moerkerke, Matthijs; Dlhosova, Tereza; Vettori, Sofie; Dzhelyova, Milena; van Winkel, Ruud; Alaerts, Kaat; Boets, Bart","year":2022,"journal":"Brain sciences, 12(9)","doi":"10.3390/brainsci12091224","pmid":"36138960","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In a double-blind, placebo-controlled, crossover trial with 31 healthy adult men, a single 24 IU dose of intranasal oxytocin did not modulate neural responses to social (faces) versus non-social (houses) stimuli. Frequency-tagging EEG clearly detected robust stimulus-specific neural responses — face processing was strongest in lateral occipito-temporal regions and house processing in medial occipital regions — confirming the methodology worked.\n\nHowever, oxytocin did not enhance social processing, nor did it increase general information salience. Bayesian analyses formally confirmed these null findings, providing evidence of absence rather than merely absence of evidence. The researchers suggested that the neurotypical participants' baseline ceiling-level performance and the personal irrelevance of the stimuli may have prevented detection of any oxytocin effect.","whyItMatters":"Oxytocin has generated enormous interest as a potential treatment for autism, social anxiety, and other conditions involving social cognition difficulties. However, if oxytocin doesn't reliably enhance social processing even in well-controlled studies, the therapeutic promise may be overstated. This null result adds important nuance to the oxytocin literature and suggests the peptide's effects may depend heavily on context, individual differences, or clinical status.","specificNumbers":"","methodology":"Double-blind, placebo-controlled, crossover trial. 31 healthy adult men received either 24 IU intranasal oxytocin or placebo in two sessions. Brain responses were measured using frequency-tagging EEG: streams of faces and houses were superimposed and presented at different frequencies (6 Hz and 7.5 Hz, counterbalanced), allowing researchers to precisely isolate neural responses to each stimulus type. Four 60-second trials were recorded per session. Bayesian analyses supplemented traditional statistics.","limitations":"Only healthy adult men were tested — results may differ in women, clinical populations, or individuals with social cognition difficulties where oxytocin effects might be more apparent. The stimuli (unfamiliar faces/houses) lacked personal relevance, which could limit sensitivity to oxytocin's effects. A single dose was used; repeated administration might produce different results. The sample size of 31, while adequate for the crossover design, is modest."},{"rthcId":"RPEP-06441","title":"Glucose-Dependent Insulinotropic Polypeptide and Substance P Mediate Emetic Response Induction by Masked Trichothecene Deoxynivalenol-3-Glucoside through Ca2+ Signaling.","authors":"Qin, Zihui; Zhang, Hua; Wu, Qinghua; Wei, Ben; Wu, Ran; Guo, Xinyi; Xiao, Huiping; Wu, Wenda","year":2022,"journal":"Toxins, 14(6)","doi":"10.3390/toxins14060371","pmid":"35737032","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"D3G caused significant vomiting in mink, linked to elevated GIP and SP levels.","whyItMatters":"Understanding how food toxins like D3G induce vomiting can help improve food safety and public health responses to foodborne illnesses.","specificNumbers":"","methodology":"The study compared emetic effects of D3G via oral and intraperitoneal routes and examined the roles of specific receptors and channels in the emetic response.","limitations":"The study was conducted in mink, which may limit the direct applicability of findings to humans."},{"rthcId":"RPEP-06442","title":"Comparison study between erenumab, fremanezumab, and galcanezumab in the preventive treatment of high frequency episodic migraine and chronic migraine.","authors":"Quintana, Simone; Russo, Marco; Manzoni, Gian Camillo; Torelli, Paola","year":2022,"journal":"Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 43(9), 5757-5758","doi":"10.1007/s10072-022-06254-x","pmid":"35802220","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"All three treatments showed excellent efficacy and tolerability.","whyItMatters":"Understanding the differences between these treatments can help tailor migraine prevention strategies for individuals. Improved treatment options can enhance quality of life for those suffering from frequent migraines.","specificNumbers":"","methodology":"This was an observational study comparing the three anti-CGRP monoclonal antibodies in migraine prevention.","limitations":"The study is observational and may not provide definitive conclusions about the comparative effectiveness of the treatments."},{"rthcId":"RPEP-06443","title":"Migraine evolution after the cessation of CGRP(-receptor) antibody prophylaxis: a prospective, longitudinal cohort study.","authors":"Raffaelli, Bianca; Terhart, Maria; Overeem, Lucas Hendrik; Mecklenburg, Jasper; Neeb, Lars; Steinicke, Maureen; Reuter, Uwe","year":2022,"journal":"Cephalalgia : an international journal of headache, 42(4-5), 326-334","doi":"10.1177/03331024211046617","pmid":"34579559","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Monthly migraine days increased from 8.2 to 12.5 after stopping treatment (p=0.999).","whyItMatters":"Understanding the effects of stopping CGRP antibody treatment can help guide migraine management strategies. This information is crucial for patients and healthcare providers when considering treatment options.","specificNumbers":"","methodology":"The study followed 62 patients who had been on CGRP antibodies for at least 8 months, analyzing their headache data before and after treatment cessation.","limitations":"The study had a relatively small sample size and focused only on a short follow-up period after treatment cessation."},{"rthcId":"RPEP-06444","title":"Resumption of migraine preventive treatment with CGRP(-receptor) antibodies after a 3-month drug holiday: a real-world experience.","authors":"Raffaelli, Bianca; Terhart, Maria; Mecklenburg, Jasper; Neeb, Lars; Overeem, Lucas Hendrik; Siebert, Anke; Steinicke, Maureen; Reuter, Uwe","year":2022,"journal":"The journal of headache and pain, 23(1), 40","doi":"10.1186/s10194-022-01417-9","pmid":"35350990","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Monthly migraine days decreased from 12.3 to 7.8 after treatment restart (p=0.001).","whyItMatters":"Understanding the effects of treatment breaks can help optimize migraine management strategies. This research supports the continued use of CGRP antibodies for effective migraine prevention.","specificNumbers":"","methodology":"The study analyzed data from 39 patients who resumed CGRP antibody treatment after a three-month drug holiday, measuring headache frequency and impact at four time points.","limitations":"The study had a small sample size and was observational, which may limit the generalizability of the findings."},{"rthcId":"RPEP-06445","title":"Dietary-Nutraceutical Properties of Oat Protein and Peptides.","authors":"Rafique, Hamad; Dong, Rui; Wang, Xiaolong; Alim, Aamina; Aadil, Rana Muhammad; Li, Lu; Zou, Liang; Hu, Xinzhong","year":2022,"journal":"Frontiers in nutrition, 9, 950400","doi":"10.3389/fnut.2022.950400","pmid":"35866075","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06446","title":"Bioactive fish collagen peptides weaken intestinal inflammation by orienting colonic macrophages phenotype through mannose receptor activation.","authors":"Rahabi, Mouna; Salon, Marie; Bruno-Bonnet, Christelle; Prat, Mélissa; Jacquemin, Godefroy; Benmoussa, Khaddouj; Alaeddine, Mohamad; Parny, Mélissa; Bernad, José; Bertrand, Bénédicte; Auffret, Yannick; Robert-Jolimaître, Pascale; Alric, Laurent; Authier, Hélène; Coste, Agnès","year":2022,"journal":"European journal of nutrition, 61(4), 2051-2066","doi":"10.1007/s00394-021-02787-7","pmid":"34999930","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Naticol®Gut-treated mice showed reduced colonic inflammation compared to DSS-only mice.","whyItMatters":"This research highlights a potential non-drug approach to managing intestinal inflammation, which could benefit individuals with gut health issues.","specificNumbers":"","methodology":"The study involved administering different treatments to mice and evaluating inflammation through various biological assays, including cytokine measurement and immune cell profiling.","limitations":"The study was conducted in mice, and results may not directly translate to humans. The sample size and specific conditions of the experiments may also limit broader applicability."},{"rthcId":"RPEP-06447","title":"Ockham's Razor for a Retinal Lesion and Acromegaly and Breaking the Vicious Circle.","authors":"Rak-Makowska, Beata; Khoo, Bernard; Sen Gupta, Piya; Plowman, P Nicholas; Grossman, Ashley B; Korbonits, Márta","year":2022,"journal":"Journal of the Endocrine Society, 6(7), bvac083","doi":"10.1210/jendso/bvac083","pmid":"35702603","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Normalization of IGF-1 levels was achieved after introducing pegvisomant, leading to improved patient outcomes.","whyItMatters":"This case highlights the importance of accurate diagnosis and targeted treatment in managing rare endocrine disorders. It also illustrates the potential long-term benefits of breaking the cycle of hormone-induced tumor growth.","specificNumbers":"","methodology":"The case study involved monitoring hormone levels and treatment responses over time in a single patient.","limitations":"As a single case study, findings may not be generalizable to all patients with acromegaly or similar conditions."},{"rthcId":"RPEP-06448","title":"Peptidergic modulation of a multi-functional central pattern generator in the pulmonate snail.","authors":"Ramakrishnan, Siddharth; Murphy, A Don","year":2022,"journal":"The Journal of experimental biology, 225(24)","doi":"10.1242/jeb.244953","pmid":"36533565","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Vertebrate GnRH agonist alters buccal motor patterns, promoting rhythmic rasping without swallowing.","whyItMatters":"Understanding how neuropeptides regulate egg-laying behaviors in snails can provide insights into similar mechanisms in other species. This knowledge may also have implications for controlling pest populations.","specificNumbers":"","methodology":"The study employed immunohistochemistry, intracellular electrophysiology, and extracellular nerve stimulation to analyze the effects of neuropeptides on snail behavior.","limitations":"The study focuses on a specific species of snail, which may limit the generalizability of the findings to other species."},{"rthcId":"RPEP-06449","title":"Improving the Therapeutic Index of Smp24, a Venom-Derived Antimicrobial Peptide: Increased Activity against Gram-Negative Bacteria.","authors":"Rawson, Kirstie M; Lacey, Melissa M; Strong, Peter N; Miller, Keith","year":2022,"journal":"International journal of molecular sciences, 23(14)","doi":"10.3390/ijms23147979","pmid":"35887325","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Systematic single amino acid substitutions at the N-terminal, mid-chain, and C-terminal positions of Smp24 revealed position-dependent structure-function relationships:\n\n- **Increased charge (N-, mid-, C-termini)**: Enhanced antimicrobial activity against Gram-negative bacteria across all positions\n- **Increased N-terminal hydrophobicity**: Reduced haemolysis and cytotoxicity — a beneficial safety improvement\n- **Increased mid-chain hydrophobicity**: Reduced both antimicrobial and cytotoxic activity — a neutral-to-detrimental change\n\nSeveral modified peptides achieved enhanced therapeutic indices compared to native Smp24, with improved antibacterial selectivity that makes them more promising as potential antibiotic drug candidates.","whyItMatters":"Antibiotic resistance is one of the greatest threats to global health, and antimicrobial peptides are promising alternatives because bacteria struggle to develop resistance against them. However, off-target toxicity has been the main barrier to clinical development. This study provides a practical engineering roadmap — specific rules about where to modify charge and hydrophobicity — that could be applied to other antimicrobial peptides, not just Smp24, to improve their safety profiles.","specificNumbers":"","methodology":"Single amino acid substitutions were systematically introduced at N-terminal, mid-chain, and C-terminal positions of the Smp24 peptide. Each variant was tested for antimicrobial activity (minimum inhibitory concentration against Gram-negative bacteria), haemolytic activity (red blood cell lysis), and mammalian cell cytotoxicity. Therapeutic indices were calculated by comparing antimicrobial potency to mammalian toxicity for each variant versus native Smp24.","limitations":"All testing was performed in vitro — in vivo pharmacokinetics, biodistribution, and efficacy in animal infection models were not assessed. The therapeutic index improvements, while encouraging, may not be sufficient for clinical use. Peptide stability in biological fluids (serum, digestive enzymes) was not tested. Only single amino acid substitutions were made; combining multiple favorable modifications could produce even better variants but was not explored."},{"rthcId":"RPEP-06450","title":"Long term effects of chronic intranasal oxytocin on adult pair bonding behavior and brain glucose uptake in titi monkeys (Plecturocebus cupreus).","authors":"Razo, Rocío Arias-Del; Velasco Vazquez, Maria de Lourdes; Turcanu, Petru; Legrand, Mathieu; Floch, Maeva; Weinstein, Tamara A R; Goetze, Leana R; Freeman, Sara M; Baxter, Alexander; Witczak, Lynea R; Sahagún, Elizabeth; Berger, Trish; Jacob, Suma; Lawrence, Rebecca H; Rothwell, Emily S; Savidge, Logan E; Solomon, Marjorie; Mendoza, Sally P; Bales, Karen L","year":2022,"journal":"Hormones and behavior, 140, 105126","doi":"10.1016/j.yhbeh.2022.105126","pmid":"35123106","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"OXT-treated monkeys showed increased affiliative behaviors, particularly tail twining, compared to saline-treated monkeys.","whyItMatters":"Understanding the effects of oxytocin on social behavior could inform treatments for social deficits in humans. This research may have implications for neurodevelopmental disorders.","specificNumbers":"","methodology":"The study involved administering intranasal oxytocin or saline to titi monkeys for six months, followed by behavioral observations and PET scans one year later.","limitations":"The study was conducted on a small sample size and in a specific species, which may limit generalizability to humans."},{"rthcId":"RPEP-06451","title":"Non-Hormonal Treatment Options for Regulation of Menstrual Cycle in Adolescents with PCOS.","authors":"Reiser, Elisabeth; Lanbach, Julia; Böttcher, Bettina; Toth, Bettina","year":2022,"journal":"Journal of clinical medicine, 12(1)","doi":"10.3390/jcm12010067","pmid":"36614868","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 164 eligible studies from a pool of 265 identified, metformin at dosages of 1500-2550 mg/day emerged as the most effective and cost-efficient non-hormonal treatment for restoring menstrual frequency in overweight adolescents with PCOS, also improving insulin sensitivity. GLP-1 receptor agonists showed effectiveness in menstrual cycle regulation. Supplements including chromium picolinate and myo-inositol also demonstrated some benefits. However, only four placebo-controlled studies were identified, with varying inclusion and exclusion criteria, highlighting the limited evidence base.","whyItMatters":"PCOS affects up to 10% of women of reproductive age, and irregular periods in adolescence can lead to long-term consequences including hypoestrogenism and bone loss. For teens who cannot take hormonal contraceptives, having effective alternatives is critical. GLP-1 receptor agonists are emerging as a promising peptide-based option that addresses both the metabolic and reproductive aspects of PCOS.","specificNumbers":"","methodology":"The researchers conducted a systematic literature search across PubMed, Cochrane, Embase, Bio-SISS, and Web of Science covering January 1998 to September 2022. From 265 identified studies, 164 were eligible for evaluation. They assessed non-hormonal pharmacological treatments including metformin, GLP-1 receptor agonists, thiazolidinediones, anti-androgens, and supplements for their effects on menstrual frequency in adolescents with PCOS.","limitations":"Only four placebo-controlled studies were identified across the entire search, severely limiting the quality of evidence. Inclusion and exclusion criteria varied widely among studies. Most data came from off-label use of medications. The review focused on adolescents, limiting applicability to adult women with PCOS. Specific GLP-1 agonist dosing and duration data were not detailed."},{"rthcId":"RPEP-06452","title":"A manganese (II)-based coordinative dendrimer with robust efficiency in intracellular peptide delivery.","authors":"Ren, Lanfang; Gao, Yang; Cheng, Yiyun","year":2022,"journal":"Bioactive materials, 9, 44-53","doi":"10.1016/j.bioactmat.2021.08.006","pmid":"34820554","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The Mn2+-coordinated polymer demonstrated the highest delivery efficiency among tested materials.","whyItMatters":"This research provides a potential new method for delivering peptide drugs, which could enhance their effectiveness in treating diseases. It may lead to better therapeutic options for intracellular targets.","specificNumbers":"","methodology":"The researchers tested various transition metal ions for their ability to facilitate peptide delivery into primary cells, focusing on manganese.","limitations":"The study primarily focuses on in vitro results, which may not directly translate to in vivo applications in humans."},{"rthcId":"RPEP-06453","title":"Identification, characterization, and antimicrobial activity of a novel big defensin discovered in a commercial bivalve mollusc, Tegillarca granosa.","authors":"Ri, Sanghyok; Zha, Shanjie; Kim, Tongchol; Ju, Kwangjin; Zhou, Weishang; Shi, Wei; Wu, Myongsik; Kim, Chunmi; Bao, Yongbo; Sun, Changsen; Liu, Guangxu","year":2022,"journal":"Fish & shellfish immunology, 124, 174-181","doi":"10.1016/j.fsi.2022.04.003","pmid":"35398526","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"TgBD has a 369 bp open reading frame and exhibits strong antimicrobial activity against Gram-positive bacteria.","whyItMatters":"Understanding antimicrobial peptides like TgBD can help in developing new strategies for disease management in aquaculture and improving food safety.","specificNumbers":"","methodology":"The study involved genomic and transcriptomic analysis to identify TgBD, followed by bioinformatics for characterization and in vitro tests for antimicrobial activity.","limitations":"The study primarily focuses on in vitro findings, which may not fully translate to in vivo effectiveness in clams or other species."},{"rthcId":"RPEP-06454","title":"Intraocular Delivery of a Collagen Mimetic Peptide Repairs Retinal Ganglion Cell Axons in Chronic and Acute Injury Models.","authors":"Ribeiro, Marcio; McGrady, Nolan R; Baratta, Robert O; Del Buono, Brian J; Schlumpf, Eric; Calkins, David J","year":2022,"journal":"International journal of molecular sciences, 23(6)","doi":"10.3390/ijms23062911","pmid":"35328332","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06455","title":"Protein Hydrolysates from Brewing By-Products as Natural Alternatives to ACE-Inhibitory Drugs for Hypertension Management.","authors":"Ribeiro-Oliveira, Rita; Martins, Zita E; Faria, Miguel Ângelo; Sousa, Joana Beatriz; Ferreira, Isabel M P L V O; Diniz, Carmen","year":2022,"journal":"Life (Basel, Switzerland), 12(10)","doi":"10.3390/life12101554","pmid":"36294989","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Final protein hydrolysates from MIX and BSG had greater ACE-inhibitory potential than captopril.","whyItMatters":"Finding natural alternatives to traditional hypertension medications could reduce side effects and improve patient compliance. This research highlights the potential of utilizing food by-products for health benefits.","specificNumbers":"","methodology":"The study involved simulating gastrointestinal digestion, intestinal absorption, and liver metabolism of protein hydrolysates, followed by testing their ACE-inhibitory potential using a fluorometric assay.","limitations":"The study was conducted in vitro, and results may not directly translate to human physiology. Further research is needed to assess bioavailability in real-world scenarios."},{"rthcId":"RPEP-06456","title":"BT8009; A Nectin-4 Targeting Bicycle Toxin Conjugate for Treatment of Solid Tumors.","authors":"Rigby, Michael; Bennett, Gavin; Chen, Liuhong; Mudd, Gemma E; Harrison, Helen; Beswick, Paul J; Van Rietschoten, Katerine; Watcham, Sophie M; Scott, Heather S; Brown, Amy N; Park, Peter U; Campbell, Carly; Haines, Eric; Lahdenranta, Johanna; Skynner, Michael J; Jeffrey, Phil; Keen, Nicholas; Lee, Kevin","year":2022,"journal":"Molecular cancer therapeutics, 21(12), 1747-1756","doi":"10.1158/1535-7163.MCT-21-0875","pmid":"36112771","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BT8009, a bicycle toxin conjugate consisting of a Nectin-4-binding bicyclic peptide linked to MMAE, demonstrated significant antitumor activity across multiple preclinical cancer models. It showed superior or equivalent activity to an enfortumab vedotin analog. Key pharmacokinetic advantages include rapid tissue diffusion and tumor penetration due to its small size, and renal elimination with a half-life of 1-2 hours in rats and non-human primates — dramatically shorter than antibody-based approaches, which may reduce systemic toxicity exposure.","whyItMatters":"Antibody-drug conjugates like enfortumab vedotin work well for bladder cancer but can cause significant toxicity that forces many patients to stop treatment. BT8009's peptide-based approach offers a potential solution: the small bicyclic peptide penetrates tumors faster and clears the body quickly, potentially delivering the same cancer-killing power with fewer side effects — and across a broader range of Nectin-4-expressing cancers.","specificNumbers":"","methodology":"The researchers designed and synthesized BT8009 using a Nectin-4-targeting bicyclic peptide coupled to MMAE via a cleavable linker. They evaluated antitumor activity in multiple preclinical tumor models across various cancer indications, conducted preclinical safety studies, and characterized pharmacokinetic properties in rats and non-human primates. Activity was compared to an analog of the approved antibody-drug conjugate enfortumab vedotin.","limitations":"All efficacy and safety data presented are from preclinical models, which may not predict human outcomes. The short half-life could require more frequent dosing. Nectin-4 expression levels vary across tumor types, and clinical efficacy beyond urothelial cancer remains to be demonstrated. The Phase 1/2 trial is ongoing and results have not yet been reported in this paper."},{"rthcId":"RPEP-06457","title":"Oxytocin, Vasopressin, and Social Behavior: From Neural Circuits to Clinical Opportunities.","authors":"Rigney, Nicole; de Vries, Geert J; Petrulis, Aras; Young, Larry J","year":2022,"journal":"Endocrinology, 163(9)","doi":"10.1210/endocr/bqac111","pmid":"35863332","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06458","title":"G protein-coupled receptor interactions and modification of signalling involving the ghrelin receptor, GHSR1a.","authors":"Ringuet, Mitchell Ty; Furness, John Barton; Furness, Sebastian George Barton","year":2022,"journal":"Journal of neuroendocrinology, 34(9), e13077","doi":"10.1111/jne.13077","pmid":"34931385","tags":["ghrelin","growth-hormone-secretagogues"],"studyType":"Review","evidenceStrength":"moderate","keyFinding":"The ghrelin receptor (GHSR1a) does far more than just trigger hunger. It physically pairs up (heterodimerizes) with at least six other brain receptors — dopamine D1 and D2, serotonin 2C, orexin, oxytocin, and melanocortin 3 receptors — and each pairing changes how both receptors signal. This receptor cross-talk explains how ghrelin influences such a wide range of functions: hunger, reward-seeking, memory, gut motility, blood sugar control, heart function, and neuroprotection.\n\nNotably, GHSR1a has high constitutive activity at some sites, meaning it sends signals even without ghrelin present. This constitutive signaling may be therapeutically important.","whyItMatters":"Many growth hormone peptides (MK-677, GHRP-6, ipamorelin) work by activating GHSR1a. Understanding how this receptor interacts with dopamine, serotonin, and oxytocin receptors explains many of the side effects and unexpected benefits users experience — from changes in mood and motivation to altered appetite and reward processing. It also opens doors for designing smarter drugs that target specific receptor pairings.","specificNumbers":"GHSR1a pairs with 6+ other GPCRs · signals via Gαq/11 pathway · has constitutive activity · ghrelin produced primarily in stomach · accesses CNS at arcuate nucleus","methodology":"Narrative review synthesizing in vitro receptor interaction studies, in vivo animal experiments, pharmacological data, and structural biology findings on GHSR1a signaling and its GPCR heterodimerization partners.","limitations":"Most GPCR heterodimerization evidence comes from in vitro cell culture systems — it remains unclear how many of these pairings are physiologically relevant in living organisms. The review presents no new data. The clinical implications of specific receptor pairings are largely theoretical at this stage."},{"rthcId":"RPEP-06459","title":"Beyond Sequencing: Prioritizing and Delivering Neoantigens for Cancer Vaccines.","authors":"Roesler, Alexander S; Anderson, Karen S","year":2022,"journal":"Methods in molecular biology (Clifton, N.J.), 2410, 649-670","doi":"10.1007/978-1-0716-1884-4_35","pmid":"34914074","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies several critical challenges in neoantigen cancer vaccine development:\n\n- Bioinformatic algorithms predict hundreds of potential neoepitopes per tumor, but most are not immunogenic\n- Few neoantigen cancer vaccines have generated strong epitope-specific T cell responses in vivo, despite promising preclinical data\n- HLA diversity means each patient's immune system recognizes different peptides, requiring fully personalized vaccines\n- Intratumoral heterogeneity of mutations means targeting one neoantigen may allow resistant clones to escape\n- Suboptimal delivery and immune activation strategies may explain the gap between preclinical and clinical results","whyItMatters":"Personalized cancer vaccines are one of the most exciting frontiers in oncology, but they have largely underdelivered in clinical trials. Understanding why — and how to fix the neoantigen selection and delivery pipeline — is essential for realizing the potential of this approach. Better peptide selection could transform cancer vaccines from a promising concept into a clinical reality.","specificNumbers":"","methodology":"Methods chapter reviewing published preclinical and clinical data on neoantigen prediction, prioritization, vaccine design, and delivery. Discusses bioinformatic approaches, HLA-peptide binding prediction, immunogenicity assessment, and combination with standard chemotherapies.","limitations":"This is a review chapter, not an original study. It reflects the state of knowledge at the time of writing (2022) and may not include the most recent clinical trial results. The discussion is primarily theoretical and does not present novel computational tools or clinical data. The chapter focuses on T cell-mediated immunity and gives less attention to antibody-based neoantigen recognition."},{"rthcId":"RPEP-06460","title":"Bioactive peptides produced by engineered probiotics and other food-grade bacteria: A review.","authors":"Romero-Luna, Haydee Eliza; Hernández-Mendoza, Adrián; González-Córdova, Aarón Fernando; Peredo-Lovillo, Audry","year":2022,"journal":"Food chemistry: X, 13, 100196","doi":"10.1016/j.fochx.2021.100196","pmid":"35498967","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06461","title":"A Potential Role for Substance P in West Nile Virus Neuropathogenesis.","authors":"Ronca, Shannon E; Gunter, Sarah M; Kairis, Rebecca Berry; Lino, Allison; Romero, Jonathan; Pautler, Robia G; Nimmo, Alan; Murray, Kristy O","year":2022,"journal":"Viruses, 14(9)","doi":"10.3390/v14091961","pmid":"36146768","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Blocking the SP/NK1R interaction improved survival and prolonged time to death in mice.","whyItMatters":"Identifying new therapeutic targets like substance P could lead to better treatments for WNND, which currently has limited options.","specificNumbers":"","methodology":"The study used a wild-type BL6 mouse model to examine the effects of substance P during West Nile virus infection.","limitations":"The study was conducted in mice, and results may not directly translate to humans; further research is needed."},{"rthcId":"RPEP-06462","title":"Impaired Brain Satiety Responses After Weight Loss in Children With Obesity.","authors":"Roth, Christian L; Melhorn, Susan J; De Leon, Mary Rosalynn B; Rowland, Maya G; Elfers, Clinton T; Huang, Alyssa; Saelens, Brian E; Schur, Ellen A","year":2022,"journal":"The Journal of clinical endocrinology and metabolism, 107(8), 2254-2266","doi":"10.1210/clinem/dgac299","pmid":"35544121","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Children with obesity showed lesser reductions in brain activation to food cues after weight loss, despite improved hormone responses.","whyItMatters":"Understanding how weight loss affects brain and hormone interactions can help in designing better obesity interventions. This knowledge is crucial for preventing weight regain in children.","specificNumbers":"","methodology":"The study involved neuroimaging and hormone assessments in 28 obese children and 17 healthy-weight children before and after a 24-week family-based behavioral treatment.","limitations":"The study had a small sample size and focused only on children aged 9-11, which may limit the generalizability of the findings."},{"rthcId":"RPEP-06463","title":"Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The STEP 8 Randomized Clinical Trial.","authors":"Rubino, Domenica M; Greenway, Frank L; Khalid, Usman; O'Neil, Patrick M; Rosenstock, Julio; Sørrig, Rasmus; Wadden, Thomas A; Wizert, Alicja; Garvey, W Timothy","year":2022,"journal":"JAMA, 327(2), 138-150","doi":"10.1001/jama.2021.23619","pmid":"35015037","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06464","title":"Structure-Activity Relationship of New Chimeric Analogs of Mastoparan from the Wasp Venom Paravespula lewisii.","authors":"Ruczyński, Jarosław; Parfianowicz, Brygida; Mucha, Piotr; Wiśniewska, Katarzyna; Piechowicz, Lidia; Rekowski, Piotr","year":2022,"journal":"International journal of molecular sciences, 23(15)","doi":"10.3390/ijms23158269","pmid":"35897844","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"MP-RIP and RIP-MP analogs exhibited high antibacterial activity against S. aureus.","whyItMatters":"The findings suggest that these new peptide analogs could lead to the development of effective antimicrobial agents. Understanding the structure-activity relationship can guide future peptide design.","specificNumbers":"","methodology":"The study involved synthesizing new peptide analogs and testing their antimicrobial activity against three bacterial strains, along with structural analysis using circular dichroism spectroscopy.","limitations":"The study primarily focuses on in vitro results, which may not fully predict in vivo effectiveness. Further research is needed to assess safety and efficacy in living organisms."},{"rthcId":"RPEP-06465","title":"Non-monotonous enzyme-assisted self-assembly profiles resulting from reaction-diffusion processes in host gels.","authors":"Runser, Jean-Yves; Criado-Gonzalez, Miryam; Fneich, Fatima; Rabineau, Morgane; Senger, Bernard; Weiss, Pierre; Jierry, Loïc; Schaaf, Pierre","year":2022,"journal":"Journal of colloid and interface science, 620, 234-241","doi":"10.1016/j.jcis.2022.03.150","pmid":"35428005","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Enzyme-assisted self-assembly resulted in at least two self-assembly maxima in patterns.","whyItMatters":"Understanding enzyme-assisted self-assembly can enhance the design of functional materials for biomedical applications. This research opens avenues for creating advanced biomaterials with specific mechanical properties.","specificNumbers":"","methodology":"The study utilized reaction-diffusion processes in hydrogels to observe peptide self-assembly patterns.","limitations":"The study primarily focuses on in vitro conditions, which may not fully translate to in vivo applications."},{"rthcId":"RPEP-06466","title":"Clinical Utilities of Anti-Müllerian Hormone.","authors":"Russell, Nicole; Gilmore, Andrea; Roudebush, William E","year":2022,"journal":"Journal of clinical medicine, 11(23)","doi":"10.3390/jcm11237209","pmid":"36498783","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review outlines AMH's key clinical roles:\n\n• AMH is produced by granulosa cells of growing follicles before they become FSH-dependent, making it a direct marker of the ovarian follicle pool\n• AMH serum concentration strongly correlates with ovarian reserve quantity and reflects ovulation potential\n• In males, Sertoli cells produce high AMH levels that suppress Müllerian duct development during embryonic sex determination, maintaining high levels until puberty\n• In females, AMH production begins in the second half of fetal life, declines through reproductive years, drops severely at menopause, and eventually becomes undetectable\n• Clinical applications include PCOS diagnosis and pathogenesis assessment, artificial reproductive technology (IVF) planning, and prediction of menopause or premature ovarian failure","whyItMatters":"AMH testing has revolutionized reproductive medicine by giving women and their doctors objective data about fertility potential. Before AMH, assessing ovarian reserve required invasive procedures or less reliable markers. A simple blood test that predicts how many eggs remain — and how a woman will respond to IVF stimulation — empowers better family planning decisions and more personalized fertility treatment.","specificNumbers":"","methodology":"This is a narrative review published in the Journal of Clinical Medicine that synthesizes existing literature on AMH biology and clinical applications across reproductive medicine, embryology, and endocrinology.","limitations":"As a narrative review, this presents a synthesis of existing knowledge rather than new data. AMH levels can vary between assay platforms, and interpretation requires clinical context — a single AMH level doesn't definitively determine fertility or infertility. The review doesn't address recent research on AMH-based contraception or AMH's potential roles beyond reproduction. Individual variability in AMH levels means population-level correlations don't always apply to individual patients."},{"rthcId":"RPEP-06467","title":"Beneficial effects of SS-31 peptide on cardiac mitochondrial dysfunction in tafazzin knockdown mice.","authors":"Russo, Silvia; De Rasmo, Domenico; Signorile, Anna; Corcelli, Angela; Lobasso, Simona","year":2022,"journal":"Scientific reports, 12(1), 19847","doi":"10.1038/s41598-022-24231-4","pmid":"36400945","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"SS-31 improved mitochondrial respiratory capacity in TazKD mice without affecting the MLCL/CL ratio.","whyItMatters":"Improving mitochondrial function could lead to better treatments for Barth Syndrome, a condition with limited therapeutic options. This research highlights the potential of SS-31 as a pharmacological agent.","specificNumbers":"","methodology":"The study used TAFAZZIN knockdown mice to assess the impact of SS-31 on mitochondrial function and lipid profiles.","limitations":"The study was conducted in mice, and results may not directly translate to humans. Further research is needed to confirm these findings in clinical settings."},{"rthcId":"RPEP-06468","title":"Drugs for Treating Obesity.","authors":"Ryan, Donna H","year":2022,"journal":"Handbook of experimental pharmacology, 274, 387-414","doi":"10.1007/164_2021_560","pmid":"34783910","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide 2.4 mg leads to an average weight loss of 15% at one year.","whyItMatters":"Understanding the effectiveness of these medications can improve treatment strategies for obesity, a major health concern linked to various diseases. Enhanced adoption of effective drugs like semaglutide could lead to better management of weight-related health issues.","specificNumbers":"","methodology":"The study reviews existing and upcoming obesity medications, focusing on their efficacy and adoption in clinical practice.","limitations":"The review primarily focuses on medication efficacy without extensive clinical trial data or long-term outcomes for all drugs discussed."},{"rthcId":"RPEP-06469","title":"Delivery of Antibiotics by Cell-Penetrating Peptides to Kill Intracellular Pathogens.","authors":"Rüter, Christian","year":2022,"journal":"Methods in molecular biology (Clifton, N.J.), 2383, 335-345","doi":"10.1007/978-1-0716-1752-6_22","pmid":"34766300","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CPPs can successfully deliver antibiotics into host cells, enhancing their effectiveness against intracellular bacteria.","whyItMatters":"This research addresses the growing issue of antibiotic resistance by providing a novel method to deliver treatments directly to hard-to-reach bacteria. It could lead to more effective therapies for infections that are currently difficult to treat.","specificNumbers":"","methodology":"The study involves conjugating cell-penetrating peptides with antimicrobial agents and conducting activity assays to test their effectiveness.","limitations":"The study primarily focuses on laboratory methods, and the translation of these findings to clinical settings requires further investigation."},{"rthcId":"RPEP-06470","title":"European Headache Federation guideline on the use of monoclonal antibodies targeting the calcitonin gene related peptide pathway for migraine prevention - 2022 update.","authors":"Sacco, Simona; Amin, Faisal Mohammad; Ashina, Messoud; Bendtsen, Lars; Deligianni, Christina I; Gil-Gouveia, Raquel; Katsarava, Zaza; MaassenVanDenBrink, Antoinette; Martelletti, Paolo; Mitsikostas, Dimos-Dimitrios; Ornello, Raffaele; Reuter, Uwe; Sanchez-Del-Rio, Margarita; Sinclair, Alexandra J; Terwindt, Gisela; Uluduz, Derya; Versijpt, Jan; Lampl, Christian","year":2022,"journal":"The journal of headache and pain, 23(1), 67","doi":"10.1186/s10194-022-01431-x","pmid":"35690723","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Moderate to high quality evidence supports eptinezumab, erenumab, fremanezumab, and galcanezumab for migraine prevention.","whyItMatters":"These updated guidelines provide healthcare professionals with evidence-based recommendations for migraine prevention. They help ensure patients receive effective and safe treatment options.","specificNumbers":"","methodology":"The guideline was developed using the GRADE approach, including a systematic review and literature analysis.","limitations":"Some clinical questions lacked sufficient evidence, relying on expert opinion rather than strong data."},{"rthcId":"RPEP-06471","title":"Cell-penetrating peptide-mediated delivery of therapeutic peptides/proteins to manage the diseases involving oxidative stress, inflammatory response and apoptosis.","authors":"Sadeghian, Issa; Heidari, Reza; Raee, Mohammad Javad; Negahdaripour, Manica","year":2022,"journal":"The Journal of pharmacy and pharmacology, 74(8), 1085-1116","doi":"10.1093/jpp/rgac038","pmid":"35728949","tags":["peptide-drug-delivery","cell-penetrating-peptides","inflammation"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"The review found that CPPs have been successfully used in both laboratory and animal studies to deliver therapeutic peptides and proteins that target three key disease processes: oxidative stress (cellular damage from reactive molecules), inflammatory response (the immune system's overreaction), and apoptosis (programmed cell death).\n\nHowever, the authors identified four fundamental obstacles preventing clinical use: CPPs lack specificity (they enter healthy and diseased cells alike), they are unstable in the body (enzymes break them down), they may be toxic at effective doses, and they can trigger immune responses. The review concludes that more research is needed to overcome these limitations before CPP-mediated delivery can be used in patients.","whyItMatters":"A huge number of therapeutic peptides and proteins have been identified that could treat conditions from neurodegenerative diseases to chronic inflammation — but many of them can't get inside cells where they need to work. Cell-penetrating peptides offer a potential universal delivery solution. If the challenges of specificity and safety can be solved, CPP technology could unlock an entire class of intracellular peptide therapies that are currently stuck in the lab.","specificNumbers":"Review covers in vitro and in vivo studies · 3 disease mechanisms targeted (oxidative stress, inflammation, apoptosis) · 4 key CPP limitations identified","methodology":"This is a narrative review article that surveyed the published scientific literature on cell-penetrating peptide-mediated delivery of therapeutic peptides and proteins. The authors examined studies covering in vitro (cell culture) and in vivo (animal) applications, focusing specifically on diseases involving oxidative stress, inflammatory pathways, and apoptosis.","limitations":"As a narrative review, this paper synthesizes existing literature but does not generate new data or perform systematic quality assessment of the studies it covers. The conclusions are only as strong as the individual studies reviewed. Publication bias may favor positive CPP results. The review does not quantify efficacy across studies or provide meta-analytic evidence."},{"rthcId":"RPEP-06472","title":"Potential of cell-penetrating peptides (CPPs) in delivery of antiviral therapeutics and vaccines.","authors":"Sadeghian, Issa; Heidari, Reza; Sadeghian, Sara; Raee, Mohammad Javad; Negahdaripour, Manica","year":2022,"journal":"European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 169, 106094","doi":"10.1016/j.ejps.2021.106094","pmid":"34896590","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CPPs have shown therapeutic efficacy in delivering antiviral agents in both in vitro and in vivo studies.","whyItMatters":"Improving the delivery of antiviral therapies could lead to better treatment options for viral infections, which currently lack effective solutions. This research highlights a promising approach to overcoming barriers in drug delivery.","specificNumbers":"","methodology":"The review synthesizes findings from various in vitro and in vivo studies on CPPs and their applications in antiviral therapy.","limitations":"The review primarily discusses findings from existing studies without original experimental data, which may limit the depth of new insights."},{"rthcId":"RPEP-06473","title":"Biotherapeutic effect of cell-penetrating peptides against microbial agents: a review.","authors":"Sadiq, Idris Zubairu; Muhammad, Aliyu; Mada, Sanusi Bello; Ibrahim, Bashiru; Umar, Umar Aliyu","year":2022,"journal":"Tissue barriers, 10(3), 1995285","doi":"10.1080/21688370.2021.1995285","pmid":"34694961","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CPPs can penetrate biological membranes and may improve drug delivery, but their effectiveness needs enhancement.","whyItMatters":"As antimicrobial resistance rises, finding new treatment methods is crucial. CPPs could provide innovative solutions for delivering therapies effectively.","specificNumbers":"","methodology":"The study is a review analyzing existing research on cell-penetrating peptides and their applications in antimicrobial therapy.","limitations":"The review does not provide new experimental data and focuses on existing literature, which may vary in quality."},{"rthcId":"RPEP-06474","title":"Genetic polymorphisms of ACE1, ACE2, and TMPRSS2 associated with COVID-19 severity: A systematic review with meta-analysis.","authors":"Saengsiwaritt, Wacharapol; Jittikoon, Jiraphun; Chaikledkaew, Usa; Udomsinprasert, Wanvisa","year":2022,"journal":"Reviews in medical virology, 32(4), e2323","doi":"10.1002/rmv.2323","pmid":"34997794","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06475","title":"Characterization of the fruit proteolytic system of Bromelia serra Griseb. (Bromeliaceae) and its application in bioactive peptides release.","authors":"Salese, Lucía; Liggieri, Constanza Silvina; Bernik, Delia Leticia; Bruno, Mariela Anahí","year":2022,"journal":"Journal of food biochemistry, 46(1), e14016","doi":"10.1111/jfbc.14016","pmid":"34811749","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The whey protein hydrolysate showed 91.9% ACE inhibition, and the casein hydrolysate had antioxidant activity of 2.89 mg/mL Trolox.","whyItMatters":"This research highlights the potential of using natural fruit enzymes in food processing to create healthier products. The findings could lead to the development of functional foods that cater to consumer demand for health benefits.","specificNumbers":"","methodology":"The researchers prepared a crude extract from the fruit and tested its proteolytic activity on various proteins at different temperatures and times.","limitations":"The study focused on a specific fruit and its enzymes, which may not be applicable to all food products or populations."},{"rthcId":"RPEP-06476","title":"Assessing the Cellular Uptake, Endosomal Escape, and Cytosolic Entry Efficiencies of Cyclic Peptides.","authors":"Salim, Heba; Pei, Dehua","year":2022,"journal":"Methods in molecular biology (Clifton, N.J.), 2371, 301-316","doi":"10.1007/978-1-0716-1689-5_16","pmid":"34596855","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The study provides a protocol for quantifying cellular uptake and endosomal escape efficiencies of cyclic peptides.","whyItMatters":"Understanding how cyclic peptides enter cells can enhance drug development, particularly for hard-to-target drug sites. This knowledge could lead to more effective treatments.","specificNumbers":"","methodology":"The authors developed a flow cytometry-based assay to measure the uptake and escape efficiencies of cyclic peptides and other biomolecules.","limitations":"The study primarily focuses on the methodology and does not provide specific experimental results or comparisons across different peptide types."},{"rthcId":"RPEP-06477","title":"Tirzepatide-Friend or Foe in Diabetic Cancer Patients?","authors":"Samuel, Samson Mathews; Varghese, Elizabeth; Kubatka, Peter; Büsselberg, Dietrich","year":2022,"journal":"Biomolecules, 12(11)","doi":"10.3390/biom12111580","pmid":"36358930","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tirzepatide may improve cancer therapy responses in diabetic patients but could also risk cancer progression.","whyItMatters":"Understanding the dual role of tirzepatide could guide treatment decisions for diabetic cancer patients, impacting their quality of life and treatment success.","specificNumbers":"","methodology":"This is a review article examining existing studies on tirzepatide's effects in diabetic cancer patients.","limitations":"The review is based on existing literature and does not present original experimental data."},{"rthcId":"RPEP-06478","title":"Role of Leu72Met of GHRL and Gln223Arg of LEPR Variants on Food Intake, Subjective Appetite, and Hunger-Satiety Hormones.","authors":"Sanchez-Murguia, Tania; Torres-Castillo, Nathaly; Magaña-de la Vega, Lisset; Rodríguez-Reyes, Saraí Citlalic; Campos-Pérez, Wendy; Martínez-López, Erika","year":2022,"journal":"Nutrients, 14(10)","doi":"10.3390/nu14102100","pmid":"35631243","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Carriers of the Leu72Met variant had higher ghrelin levels and sugar intake compared to non-carriers.","whyItMatters":"Understanding the genetic factors influencing appetite can help in developing targeted strategies for obesity prevention and management. This research may lead to personalized dietary recommendations based on genetic profiles.","specificNumbers":"","methodology":"The study involved 132 participants who recorded their diets over three days and had their appetite measured using visual scales, alongside hormone level assessments after fasting and post-meal.","limitations":"The study focused only on individuals with normal BMIs, limiting the generalizability of the findings to broader populations. Additionally, the sample size may not be large enough to capture all variations."},{"rthcId":"RPEP-06479","title":"Novel Alligator Cathelicidin As-CATH8 Demonstrates Anti-Infective Activity against Clinically Relevant and Crocodylian Bacterial Pathogens.","authors":"Santana, Felix L; Estrada, Karel; Alford, Morgan A; Wu, Bing C; Dostert, Melanie; Pedraz, Lucas; Akhoundsadegh, Noushin; Kalsi, Pavneet; Haney, Evan F; Straus, Suzana K; Corzo, Gerardo; Hancock, Robert E W","year":2022,"journal":"Antibiotics (Basel, Switzerland), 11(11)","doi":"10.3390/antibiotics11111603","pmid":"36421248","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"As-CATH8 demonstrated potent in vitro activity against antibiotic-resistant bacteria, outperforming human LL-37.","whyItMatters":"With rising antibiotic resistance, new antimicrobial agents are urgently needed. As-CATH8 could provide an effective alternative for treating resistant infections.","specificNumbers":"","methodology":"The study involved genomic screening of four crocodylian species, synthesis of cathelicidins, and testing their antimicrobial activity in vitro and in a murine model.","limitations":"The study primarily involves in vitro and animal models, which may not fully predict human responses."},{"rthcId":"RPEP-06480","title":"Metabolic Fate and Bioavailability of Food-Derived Peptides: Are Normal Peptides Passed through the Intestinal Layer To Exert Biological Effects via Proposed Mechanisms?","authors":"Sato, Kenji","year":2022,"journal":"Journal of agricultural and food chemistry, 70(5), 1461-1466","doi":"10.1021/acs.jafc.1c07438","pmid":"35104135","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Food-derived peptides may be metabolized into active compounds or act through different mechanisms than previously proposed.","whyItMatters":"Understanding how food-derived peptides function in the body can help improve dietary recommendations and health interventions. It also highlights the need for more research into their metabolic pathways.","specificNumbers":"","methodology":"The study reviews existing literature on the metabolism and bioavailability of food-derived peptides.","limitations":"The study primarily discusses existing literature without presenting new experimental data."},{"rthcId":"RPEP-06481","title":"Potent bactericidal activity of reduced cryptdin-4 derived from its hydrophobicity and mediated by bacterial membrane disruption.","authors":"Sato, Yuji; Wang, Yi; Song, Yuchi; Geng, Weiming; Yan, Shaonan; Nakamura, Kiminori; Kikukawa, Takashi; Demura, Makoto; Ayabe, Tokiyoshi; Aizawa, Tomoyasu","year":2022,"journal":"Amino acids, 54(2), 289-297","doi":"10.1007/s00726-021-03115-3","pmid":"35037097","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The reduced (unfolded) form of cryptdin-4 (Crp4red) killed both commensal and non-commensal bacteria, while the oxidized (folded) form (Crp4ox) only killed non-commensal bacteria. The key difference was hydrophobicity — Crp4red's exposed hydrophobic regions allowed it to insert deeply into bacterial membranes and disrupt them.\n\nWhen researchers blocked the cysteine thiol groups with N-ethylmaleimide (NEM-Crp4), the resulting peptide mimicked Crp4red's high hydrophobicity and also killed commensal bacteria. Conversely, blocking electrostatic interactions abolished killing by both forms, confirming that initial membrane binding via electrostatic attraction is required before hydrophobic insertion can occur. Liposome leakage assays using lipids from commensal bacteria confirmed that membrane disruption correlated directly with bactericidal activity.","whyItMatters":"Most antimicrobial peptide research focuses on their folded (oxidized) forms, but this study shows the unfolded form can be far more potent. Understanding that hydrophobicity — not just charge — drives selectivity against gut commensal bacteria could inform the design of next-generation antimicrobial peptides that can selectively target specific bacterial populations.","specificNumbers":"6 cysteine residues modified · 3 disulfide bonds in oxidized form · Correlation between hydrophobicity and membrane insertion confirmed","methodology":"Researchers compared four versions of cryptdin-4: oxidized (Crp4ox), reduced (Crp4red), all cysteines replaced with serine (6C/S-Crp4), and thiol-blocked (NEM-Crp4). Each was tested for bactericidal activity against commensal and non-commensal bacteria. Hydrophobicity was measured and correlated with membrane insertion ability. Electrostatic interaction inhibition experiments identified the initial binding mechanism, and liposome leakage assays using extracted bacterial lipids confirmed membrane disruption as the killing mechanism.","limitations":"This is entirely an in vitro study — all experiments were conducted in lab dishes with purified peptides and bacteria. The results have not been validated in living animals. The study used mouse cryptdin-4, which has no direct human equivalent (humans produce different alpha-defensins). Whether these hydrophobicity-driven mechanisms apply to human defensins remains to be tested."},{"rthcId":"RPEP-06482","title":"Anti-inflammatory effects of GLP-1 in patients with COVID-19.","authors":"Sazgarnejad, Saharnaz; Yazdanpanah, Niloufar; Rezaei, Nima","year":2022,"journal":"Expert review of anti-infective therapy, 20(3), 373-381","doi":"10.1080/14787210.2021.1964955","pmid":"34348067","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RAs may reduce inflammation and modify risk factors for severe COVID-19 complications.","whyItMatters":"With no definitive treatment for COVID-19, exploring existing medications like GLP-1 RAs could lead to new therapeutic strategies. Understanding their anti-inflammatory properties may improve patient outcomes.","specificNumbers":"","methodology":"This is a review study that analyzed existing literature on GLP-1 RAs and their effects on COVID-19.","limitations":"The study is a review and does not present new experimental data or clinical trials."},{"rthcId":"RPEP-06483","title":"Thymosin β4 is essential for thrombus formation by controlling the G-actin/F-actin equilibrium in platelets.","authors":"Scheller, Inga; Beck, Sarah; Göb, Vanessa; Gross, Carina; Neagoe, Raluca A I; Aurbach, Katja; Bender, Markus; Stegner, David; Nagy, Zoltan; Nieswandt, Bernhard","year":2022,"journal":"Haematologica, 107(12), 2846-2858","doi":"10.3324/haematol.2021.278537","pmid":"34348450","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Thymosin β4 knockout mice developed macrothrombocytopenia (low platelet count with mildly enlarged platelets) due to defective proplatelet formation from megakaryocytes, both in vitro and in vivo. The remaining platelets had markedly decreased G-actin and increased F-actin levels, disrupting the normal actin equilibrium.\n\nThis actin imbalance produced paradoxical effects: accelerated platelet spreading on fibrinogen and faster clot retraction, but impaired platelet activation through the glycoprotein VI collagen receptor pathway due to defective ITAM signaling. The net result was impaired aggregate formation under flow conditions, protection from occlusive arterial thrombus formation in vivo, and increased tail bleeding times — demonstrating that thymosin β4 is essential for both platelet production and functional thrombus stability.","whyItMatters":"Thymosin β4 is being investigated as a therapeutic peptide for wound healing, cardiac repair, and other regenerative applications. Understanding its critical role in platelet function and blood clotting is essential for predicting potential side effects of thymosin β4-based therapies, and could also open new approaches to preventing arterial thrombosis — a leading cause of heart attacks and strokes.","specificNumbers":"","methodology":"Researchers generated constitutive Tmsb4x knockout mice and compared them to wild-type controls. They assessed platelet counts, volume, and lifespan; examined megakaryocyte numbers and proplatelet formation in bone marrow and spleen; measured G-actin and F-actin levels in platelets; tested platelet activation, spreading, and aggregation under flow conditions; and performed in vivo arterial thrombosis and tail bleeding time assays. ITAM signaling downstream of glycoprotein VI was assessed to identify the molecular mechanism of activation defects.","limitations":"This is a mouse knockout study, and the complete absence of thymosin β4 from birth is quite different from therapeutic peptide administration in adults. The phenotype in mice may not directly translate to humans, where compensatory mechanisms could differ. The study used constitutive (whole-body) knockout rather than platelet-specific deletion, so some effects could be influenced by thymosin β4 loss in other cell types. Long-term consequences of the macrothrombocytopenia were not assessed."},{"rthcId":"RPEP-06484","title":"Investigation of the Role of Hydrophobic Amino Acids on the Structure-Activity Relationship in the Antimicrobial Venom Peptide Ponericin L1.","authors":"Schifano, Nicholas P; Caputo, Gregory A","year":2022,"journal":"The Journal of membrane biology, 255(4-5), 537-551","doi":"10.1007/s00232-021-00204-y","pmid":"34792624","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The native hydrophobic residues in ponericin L1 were uniformly replaced with either leucine, isoleucine, phenylalanine, alanine, or valine. Several variants showed enhanced antimicrobial activity compared to the parent peptide, while others lost activity entirely.\n\nMost notably, the valine variant lost all antimicrobial activity and all ability to interact with lipid bilayers. The variants showed varying degrees of membrane interaction, with some responses depending on the lipid composition of the target membrane. Spectroscopic analysis revealed that the substitutions altered both secondary structure and membrane binding behavior. The results demonstrate that peptide secondary structure, amino acid composition, and hydrophobicity must be carefully balanced — getting any one factor wrong can result in either non-specific binding or complete loss of function.","whyItMatters":"Antibiotic resistance is a growing global health crisis, and antimicrobial peptides (AMPs) from natural sources like venom are promising alternative weapons against drug-resistant bacteria. However, many venom peptides are too toxic for therapeutic use. Understanding exactly which amino acids drive antimicrobial activity versus toxicity is essential for engineering safer, more effective peptide antibiotics. This study provides concrete design rules for one of the most important structural parameters — hydrophobic residue selection.","specificNumbers":"","methodology":"The ponericin L1 peptide sequence was modified by uniformly replacing all native hydrophobic residues with one of five hydrophobic amino acids (Leu, Ile, Phe, Ala, or Val). Each variant was analyzed using spectroscopic techniques (likely circular dichroism and fluorescence spectroscopy) to assess secondary structure and membrane interaction. Microbiological assays measured antimicrobial efficacy against bacterial targets. Lipid bilayer interaction studies examined how membrane composition affected peptide binding behavior.","limitations":"All experiments were conducted in vitro, and antimicrobial activity in lab conditions may not translate to efficacy in living organisms where factors like protein binding, enzymatic degradation, and immune interactions come into play. The study used uniform substitution of all hydrophobic residues simultaneously, which does not reveal the contribution of individual positions. Cytotoxicity data for the modified variants is not detailed in the abstract. Specific bacterial strains tested and MIC values are not reported in the abstract."},{"rthcId":"RPEP-06485","title":"PATAS, a First-in-Class Therapeutic Peptide Biologic, Improves Whole-Body Insulin Resistance and Associated Comorbidities In Vivo.","authors":"Schreyer, Edwige; Obringer, Cathy; Messaddeq, Nadia; Kieffer, Bruno; Zimmet, Paul; Fleming, Alexander; Geberhiwot, Tarekegn; Marion, Vincent","year":2022,"journal":"Diabetes, 71(9), 2034-2047","doi":"10.2337/db22-0058","pmid":"35822820","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"PATAS is a stapled peptide derived from the kinase domain of PKCα that disrupts the ALMS1-PKCα protein interaction in adipocytes. The mechanistic pathway was identified through studying Alström syndrome, an ultrarare genetic disorder caused by ALMS1 inactivation that results in severe insulin resistance.\n\nIn cultured human adipocytes, PATAS triggered insulin-independent glucose absorption, de novo lipogenesis (fat synthesis from glucose), and cellular glucose utilization — effectively bypassing the insulin signaling pathway.\n\nIn vivo in rodent models, PATAS reduced whole-body insulin resistance and improved glucose intolerance, fasting glucose levels, liver steatosis (fatty liver), and liver fibrosis. Importantly, the study also showed that reactivating ALMS1 specifically in adipocytes reversed all these metabolic phenotypes, confirming that the adipocyte is the key therapeutic target.","whyItMatters":"Current diabetes drugs primarily work by increasing insulin production or sensitivity through known pathways. PATAS represents a completely new approach — it bypasses insulin signaling entirely by targeting a previously unknown mechanism in fat cells. If it works in humans, it could help patients with severe insulin resistance who don't respond well to existing therapies, and its effects on liver steatosis and fibrosis suggest broader metabolic benefits beyond blood sugar control.","specificNumbers":"","methodology":"The researchers first identified the ALMS1-PKCα protein interaction in adipocytes through genetic studies of Alström syndrome. They screened α-helices in the PKCα kinase domain to find a peptide sequence that disrupted this interaction, then created a stapled (chemically stabilized) version called PATAS. The peptide was tested in vitro on cultured human adipocytes measuring glucose absorption, lipogenesis, and glucose utilization. In vivo testing in rodent models measured insulin resistance, glucose tolerance, fasting glucose, and liver histopathology.","limitations":"All in vivo results are from rodent models, which may not translate to humans. The abstract does not report specific quantitative improvements (fold-changes, percentages) for the metabolic endpoints. Long-term safety, dosing optimization, and pharmacokinetics in humans are unknown. The stapled peptide's stability, bioavailability, and manufacturing scalability are not discussed. As a first-in-class compound, no clinical trial data exist."},{"rthcId":"RPEP-06486","title":"Enhanced In Vitro Expression of Filaggrin and Antimicrobial Peptides Following Application of Glycosaminoglycans and a Sphingomyelin-Rich Lipid Extract.","authors":"Segarra, Sergi; Naiken, Tanesha; Garnier, Julien; Hamon, Valérie; Coussay, Nathalie; Bernard, François-Xavier","year":2022,"journal":"Veterinary sciences, 9(7)","doi":"10.3390/vetsci9070323","pmid":"35878340","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Filaggrin expression increased by 210% with the combination of lipid extract and GAGs.","whyItMatters":"Improving skin barrier function and antimicrobial peptide levels could significantly benefit dogs suffering from atopic dermatitis.","specificNumbers":"","methodology":"The study involved in vitro testing on reconstructed human epidermis and normal human epidermal keratinocyte cultures using specific extracts.","limitations":"The study was conducted in vitro, so results may not directly translate to in vivo applications in dogs."},{"rthcId":"RPEP-06487","title":"Lactoferricins impair the cytosolic membrane of Escherichia coli within a few seconds and accumulate inside the cell.","authors":"Semeraro, Enrico F; Marx, Lisa; Mandl, Johannes; Letofsky-Papst, Ilse; Mayrhofer, Claudia; Frewein, Moritz P K; Scott, Haden L; Prévost, Sylvain; Bergler, Helmut; Lohner, Karl; Pabst, Georg","year":2022,"journal":"eLife, 11","doi":"10.7554/eLife.72850","pmid":"35670565","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Using millisecond time-resolved synchrotron small-angle X-ray scattering, researchers captured the real-time response of E. coli to lactoferricin-derived AMPs across length scales from whole cells down to lipid packing. Key findings:\n\n1. The peptides permeabilized the cytosolic membrane in less than 3 seconds — much faster than previously considered.\n2. Final intracellular peptide concentrations reached ~80–100 mM, suggesting efficient obstruction of physiologically important processes as the primary killing mechanism.\n3. Membrane damage and leakage occurred even at sublethal concentrations, showing that membrane permeabilization is a necessary but not sufficient condition for killing.\n4. The most efficient peptide studied excelled in both speed of membrane permeabilization and lowest intracellular concentration needed to inhibit bacterial growth.","whyItMatters":"This study fundamentally changes our understanding of how antimicrobial peptides kill bacteria. The longstanding assumption was that membrane disruption is the primary killing mechanism, but these results show it's actually what happens after the peptides get inside that matters most. This insight is crucial for designing better antimicrobial peptides — rather than focusing solely on membrane-disrupting ability, researchers should also optimize intracellular activity.","specificNumbers":"","methodology":"Researchers used millisecond time-resolved synchrotron small-angle X-ray scattering (SAXS) at a synchrotron facility to observe the real-time structural changes in living E. coli upon exposure to lactoferricin-derived antimicrobial peptides. A multiscale scattering data analysis was coupled with biophysical assays for peptide partitioning between bacterial membranes and the surrounding medium. This allowed simultaneous observation at both microscopic (cell-level) and nanoscopic (lipid-level) scales.","limitations":"The study focused exclusively on E. coli (a Gram-negative bacterium) and results may differ for Gram-positive bacteria, which have different membrane architectures. The synchrotron experiments were performed under specific laboratory conditions that may not fully replicate physiological environments. The exact intracellular processes disrupted by the accumulated peptides were not identified. The study used lactoferricin-derived peptides specifically, and the findings may not generalize to all antimicrobial peptide classes."},{"rthcId":"RPEP-06488","title":"In Silico Analysis of Bioactive Peptides Produced from Underutilized Sea Cucumber By-Products-A Bioinformatics Approach.","authors":"Senadheera, Tharindu R L; Hossain, Abul; Dave, Deepika; Shahidi, Fereidoon","year":2022,"journal":"Marine drugs, 20(10)","doi":"10.3390/md20100610","pmid":"36286434","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"All identified peptides were non-toxic and showed favorable functional properties.","whyItMatters":"This research highlights the potential of using waste materials from sea cucumbers, promoting sustainability and innovation in food and pharmaceutical industries.","specificNumbers":"","methodology":"The study used bioinformatics tools to analyze peptides from sea cucumber by-products, including LC-MS/MS and in silico simulations.","limitations":"The study is based on in silico methods, which may not fully predict real-world effects in humans."},{"rthcId":"RPEP-06489","title":"Treatment of migraine with monoclonal antibodies.","authors":"Serra López-Matencio, José María; Gago-Veiga, Ana Beatriz; Gómez, Manuel; Alañón Plaza, Estefanía; Mejía, Gina Paola; González-Gay, Miguel Ángel; Castañeda, Santos","year":2022,"journal":"Expert opinion on biological therapy, 22(6), 707-716","doi":"10.1080/14712598.2022.2072207","pmid":"35502612","tags":[],"studyType":"review","evidenceStrength":"strong","keyFinding":"Anti-CGRP monoclonal antibodies represent a paradigm shift in migraine treatment — the first drugs designed specifically around migraine pathophysiology. These drugs target calcitonin gene-related peptide (CGRP), a neuropeptide that plays a central role in causing migraine attacks. The review concludes that anti-CGRP mAbs are highly effective but face real-world challenges: high cost, limited long-term experience, and the need for multidisciplinary teams to identify which patients will benefit most.\n\nThe review emphasizes that proper patient selection and cost-effective prescribing strategies are essential as these drugs move from clinical trials into routine practice.","whyItMatters":"For decades, migraine treatments were borrowed from other conditions — blood pressure drugs, antidepressants, anti-seizure medications. Anti-CGRP antibodies are the first migraine drugs designed from the ground up based on understanding the neuropeptide that triggers attacks. This represents one of the most successful examples of peptide biology leading directly to a new drug class, and it has transformed care for millions of chronic migraine patients who failed older treatments.","specificNumbers":"CGRP identified as key migraine neuropeptide · multiple anti-CGRP mAbs developed · high efficacy reported · high cost identified as barrier · multidisciplinary teams recommended","methodology":"Narrative review of the literature on anti-CGRP monoclonal antibodies for migraine, covering pathophysiology, drug mechanisms, clinical evidence, practical management considerations, and cost-effectiveness.","limitations":"Narrative review without systematic methodology. Mostly summarizes existing knowledge without new data. Limited discussion of specific efficacy numbers or head-to-head comparisons. Published in 2022 — newer data on long-term safety and real-world effectiveness has since accumulated."},{"rthcId":"RPEP-06490","title":"Treatment of resistant chronic migraine with anti-CGRP monoclonal antibodies: a systematic review.","authors":"Sevivas, Hugo; Fresco, Paula","year":2022,"journal":"European journal of medical research, 27(1), 86","doi":"10.1186/s40001-022-00716-w","pmid":"35659086","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"All anti-CGRP monoclonal antibodies reduced monthly migraine days and improved quality of life without differing in safety from placebo.","whyItMatters":"This research provides valuable insights into effective treatments for chronic migraines, a condition often resistant to standard therapies. It may help healthcare professionals make informed treatment decisions.","specificNumbers":"","methodology":"The study is a systematic review of randomized controlled trials analyzing anti-CGRP monoclonal antibodies in chronic migraine patients.","limitations":"The review is limited to four studies, which may not encompass all available data on anti-CGRP therapies."},{"rthcId":"RPEP-06491","title":"Advanced Pancreatic Cancer Patient Benefit From Personalized Neoantigen Nanovaccine Based Immunotherapy: A Case Report.","authors":"Shao, Jie; Liu, Qin; Shen, Jie; Qian, Xiaoping; Yan, Jing; Zhu, Yahui; Qiu, Xin; Lu, Changchang; Cen, Lanqi; Tian, Manman; Du, Juan; Liu, Baorui","year":2022,"journal":"Frontiers in immunology, 13, 799026","doi":"10.3389/fimmu.2022.799026","pmid":"35273594","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A personalized neoantigen nanovaccine combined with anti-PD-1 antibody therapy resulted in an overall survival of 10.5 months in an advanced pancreatic cancer patient who had relapsed on third-line treatment.\n\nThe patient developed peptide-specific T-cell responses against 9 of the 12 vaccine peptides, confirmed by IFN-γ ELISPOT and intracellular cytokine staining. These robust and sustained neoantigen-specific T cell responses suggest the vaccine successfully activated targeted anti-tumor immunity.","whyItMatters":"Pancreatic cancer is one of the deadliest cancers, with very few effective treatments once it becomes advanced. This case demonstrates that personalized peptide vaccines delivered via nanoparticles can induce meaningful immune responses even in a cancer type traditionally considered resistant to immunotherapy. Combined with checkpoint inhibitors, this approach represents a promising new direction for treating cancers with poor prognoses.","specificNumbers":"","methodology":"This was a single-patient case report from a clinical study combining neoantigen nanovaccine with anti-PD-1 antibody. The process involved whole-exome sequencing of the patient's tumor to identify individual mutations, computational prediction of neoepitopes, and custom manufacturing of a nanovaccine containing 12 peptides. The vaccine was administered after relapse on third-line therapy. Clinical outcomes and circulating immune responses were assessed using IFN-γ ELISPOT assays and intracellular cytokine staining.","limitations":"This is a single case report, which provides the lowest level of clinical evidence. Results from one patient cannot be generalized to the broader pancreatic cancer population. There is no control group for comparison, so it's impossible to determine how much of the outcome was due to the vaccine versus the anti-PD-1 therapy or natural disease course. The manufacturing process for personalized nanovaccines is complex and time-consuming, raising questions about scalability."},{"rthcId":"RPEP-06492","title":"Exploring the TEMPO-Oxidized Nanofibrillar Cellulose and Short Ionic-Complementary Peptide Composite Hydrogel as Biofunctional Cellular Scaffolds.","authors":"Sharma, Pooja; Pal, Vijay K; Kaur, Harsimran; Roy, Sangita","year":2022,"journal":"Biomacromolecules, 23(6), 2496-2511","doi":"10.1021/acs.biomac.2c00234","pmid":"35522599","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Key results from the composite hydrogel study:\n\n- Differential peptide doping into TO-NFC hydrogel tuned surface hydrophobicity, microporosity, and mechanical stiffness\n- Different cellular responses observed at varying TO-NFC:Nap-FEFK ratios\n- 10:1 (w/w) ratio showed enhanced cellular survival and proliferation in 2D culture\n- 10:1 composite matched Matrigel performance in 3D cell culture conditions\n- No significant inflammatory response in Raw macrophage cells\n- Scaffolds supported immune cell survival and proliferation\n- Demonstrates multicomponent self-assembly as a viable approach for ECM-mimicking biomaterials","whyItMatters":"Matrigel is widely used for 3D cell culture and tissue engineering but has major drawbacks — it's derived from mouse tumor tissue, has batch-to-batch variability, and is expensive. A peptide-cellulose hydrogel that matches its performance could provide a reproducible, non-animal-derived, tunable alternative for regenerative medicine and drug testing applications.","specificNumbers":"","methodology":"TEMPO-oxidized nanofibrillar cellulose (TO-NFC) was combined with the ionic complementary peptide Nap-FEFK at various ratios to fabricate supramolecular hydrogels. Scaffolds were characterized for hydrophobicity, microporosity, and mechanical stiffness. Cellular responses were tested in both 2D and 3D culture, comparing to Matrigel. Inflammatory response was assessed using Raw macrophage cells.","limitations":"All testing was conducted in vitro using cell cultures. Performance in living organisms (in vivo), including immune compatibility, biodegradation, and tissue integration, was not assessed. Only one cell type was used for proliferation studies. Long-term stability and scalability of the hydrogel production were not addressed. The comparison to Matrigel was limited to cell proliferation, not functional tissue formation."},{"rthcId":"RPEP-06493","title":"Self-Assembled Peptide Hydrogel for Accelerated Wound Healing: Impact of N-Terminal and C-Terminal Modifications.","authors":"Sharma, Rohit; Tomar, Shruti; Puri, Sanjeev; Wangoo, Nishima","year":2022,"journal":"Chembiochem : a European journal of chemical biology, 23(22), e202200499","doi":"10.1002/cbic.202200499","pmid":"36177524","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Fmoc hydrogels showed a 40% faster healing rate compared to acetylated hydrogels.","whyItMatters":"This research highlights the potential of peptide-based hydrogels as advanced wound dressings, which could lead to improved healing outcomes for patients. Enhanced wound care products are crucial for better recovery and infection prevention.","specificNumbers":"","methodology":"The study involved preparing and comparing three hexapeptide-based hydrogels, assessing their biological effects in vitro and in vivo using a mouse model.","limitations":"The study was conducted in a mouse model, which may not fully replicate human healing processes."},{"rthcId":"RPEP-06494","title":"Novel Antioxidant Collagen Peptides of Siberian Sturgeon (Acipenserbaerii) Cartilages: The Preparation, Characterization, and Cytoprotection of H2O2-Damaged Human Umbilical Vein Endothelial Cells (HUVECs).","authors":"Sheng, Yan; Qiu, Yi-Ting; Wang, Yu-Mei; Chi, Chang-Feng; Wang, Bin","year":2022,"journal":"Marine drugs, 20(5)","doi":"10.3390/md20050325","pmid":"35621976","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Three peptides (GEYGFE, PSVSLT, IELFPGLP) showed strong antioxidant activity with EC50 values of 1.05-1.38 mg/mL.","whyItMatters":"These findings highlight a way to utilize fish by-products for health benefits, potentially leading to new antioxidant supplements for chronic disease prevention.","specificNumbers":"","methodology":"The cartilage was processed using proteases to create hydrolysates, from which antioxidant peptides were isolated and tested for their protective effects on human endothelial cells.","limitations":"The study primarily focuses on in vitro results, which may not fully translate to in vivo effectiveness in humans."},{"rthcId":"RPEP-06495","title":"A Frog-Derived Cathelicidin Peptide with Dual Antimicrobial and Immunomodulatory Activities Effectively Ameliorates Staphylococcus aureus-Induced Peritonitis in Mice.","authors":"Shi, Jie; Wu, Jing; Chen, Qian; Shen, Yan; Mi, Kai; Yang, Hailong; Mu, Lixian","year":2022,"journal":"ACS infectious diseases, 8(12), 2464-2479","doi":"10.1021/acsinfecdis.2c00260","pmid":"36378028","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Nv-CATH (sequence: NCNFLCKVKQRLRSVSSTSHIGMAIPRPRG), a 30-residue cathelicidin peptide from frog skin, demonstrated:\n\n- Broad-spectrum antimicrobial activity against both Gram-positive and Gram-negative bacteria\n- Significant protection of mice from lethal S. aureus infections\n- Suppression of harmful inflammatory responses by reducing production of NO, IL-6, TNF-α, and IL-1β\n- Anti-inflammatory action through the NF-κB-NLRP3 and MAPK signaling pathways (confirmed both in vitro and in vivo)\n- Immune cell recruitment by stimulating CXCL1, CXCL2, and CCL2 chemokine production in macrophages\n- Enhanced immune cell killing by modestly promoting neutrophil phagocytosis and NET formation\n\nThe dual antimicrobial-immunomodulatory mechanism sets this peptide apart from conventional antibiotics.","whyItMatters":"Antibiotic resistance is one of the most pressing public health threats, with drug-resistant Staphylococcus aureus (MRSA) causing thousands of deaths annually. Conventional antibiotics only kill bacteria without addressing the inflammatory damage that severe infections cause. Nv-CATH's ability to both kill bacteria and modulate inflammation represents a fundamentally different approach — one that could be more effective against resistant infections and cause less collateral tissue damage.","specificNumbers":"","methodology":"The researchers isolated and identified Nv-CATH from the skin of the frog Nanorana ventripunctata. Antimicrobial activity was tested in vitro against panels of Gram-positive and Gram-negative bacteria. Immunomodulatory effects were characterized in cell culture by measuring cytokine production, signaling pathway activation (NF-κB-NLRP3 and MAPK), chemokine secretion, and neutrophil function. In vivo efficacy was tested in a lethal S. aureus peritonitis mouse model.","limitations":"All in vivo work was done in mice, which may not predict human responses. The specific minimum inhibitory concentrations against individual bacterial species are not detailed in the abstract. Toxicity to human cells, stability in biological fluids, and pharmacokinetics have not been reported. The peptide's efficacy against clinically relevant drug-resistant strains (like MRSA) is not explicitly stated. Translation from a natural frog peptide to a clinical drug would require extensive optimization."},{"rthcId":"RPEP-06496","title":"The effect of dietary supplementation with blueberry, cyanidin-3-O-β-glucoside, yoghurt and its peptides on gene expression associated with glucose metabolism in skeletal muscle obtained from a high-fat-high-carbohydrate diet induced obesity model.","authors":"Shi, Min; Mathai, Michael L; Xu, Guoqin; Su, Xiao Q; McAinch, Andrew J","year":2022,"journal":"PloS one, 17(9), e0270306","doi":"10.1371/journal.pone.0270306","pmid":"36112580","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Yogurt increased beneficial gene expression and decreased harmful gene expression in muscle tissues.","whyItMatters":"Understanding how diet influences gene expression can help develop dietary strategies for managing obesity and type 2 diabetes.","specificNumbers":"","methodology":"The study used a high-fat-high-carbohydrate diet-induced obesity model in mice to assess gene expression changes in skeletal muscle.","limitations":"The study was conducted in mice, so results may not directly translate to humans. Additionally, the long-term effects of these dietary supplements were not assessed."},{"rthcId":"RPEP-06497","title":"Lower human defensin 5 in elderly people compared to middle-aged is associated with differences in the intestinal microbiota composition: the DOSANCO Health Study.","authors":"Shimizu, Yu; Nakamura, Kiminori; Kikuchi, Mani; Ukawa, Shigekazu; Nakamura, Koshi; Okada, Emiko; Imae, Akihiro; Nakagawa, Takafumi; Yamamura, Ryodai; Tamakoshi, Akiko; Ayabe, Tokiyoshi","year":2022,"journal":"GeroScience, 44(2), 997-1009","doi":"10.1007/s11357-021-00398-y","pmid":"34105106","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Elderly individuals had significantly lower HD5 levels (r = -0.307, p < 0.001) and different gut microbiota composition.","whyItMatters":"Understanding the relationship between defensin levels and gut microbiota can help explain age-related health risks. This research may guide future strategies for improving gut health in the elderly.","specificNumbers":"","methodology":"Fecal samples were collected from 196 healthy Japanese participants, and HD5 concentrations were measured to assess correlations with gut microbiota.","limitations":"The study is limited to a specific population (Japanese individuals) and may not be generalizable to other ethnic groups."},{"rthcId":"RPEP-06498","title":"Exogenous Ceramide Serves as a Precursor to Endogenous Ceramide Synthesis and as a Modulator of Keratinocyte Differentiation.","authors":"Shin, Kyong-Oh; Mihara, Hisashi; Ishida, Kenya; Uchida, Yoshikazu; Park, Kyungho","year":2022,"journal":"Cells, 11(11)","doi":"10.3390/cells11111742","pmid":"35681438","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"NDS increased involucrin by 2.5 times and cathelicidin levels significantly compared to NP and control.","whyItMatters":"Understanding how ceramides influence skin health can lead to better skincare products and treatments for skin barrier disorders.","specificNumbers":"","methodology":"The researchers treated cultured human keratinocytes with NP and NDS to assess their effects on cell differentiation and antimicrobial peptide production.","limitations":"The study was conducted in vitro, so results may not fully translate to human skin in vivo."},{"rthcId":"RPEP-06499","title":"Designing a Novel Functional Peptide With Dual Antimicrobial and Anti-inflammatory Activities via in Silico Methods.","authors":"Shin, Min Kyoung; Lee, Byungjo; Kim, Seung Tae; Yoo, Jung Sun; Sung, Jung-Suk","year":2022,"journal":"Frontiers in immunology, 13, 821070","doi":"10.3389/fimmu.2022.821070","pmid":"35432369","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The peptides inhibited both gram-negative and gram-positive bacteria and reduced pro-inflammatory mediators.","whyItMatters":"Developing new antimicrobial and anti-inflammatory agents is crucial in addressing antibiotic resistance and inflammatory diseases. These findings could lead to innovative treatments derived from natural sources.","specificNumbers":"","methodology":"The study used in silico methods to design peptides based on spider venom, followed by functional validation in laboratory tests.","limitations":"The study was conducted in vitro, and results may not directly translate to human applications."},{"rthcId":"RPEP-06500","title":"Combination treatment of radiofrequency ablation and peptide neoantigen vaccination: Promising modality for future cancer immunotherapy.","authors":"Shou, Jiawei; Mo, Fan; Zhang, Shanshan; Lu, Lantian; Han, Ning; Liu, Liang; Qiu, Min; Li, Hongseng; Han, Weidong; Ma, Dongying; Guo, Xiaojie; Guo, Qianpeng; Huang, Qinxue; Zhang, Xiaomeng; Ye, Shengli; Pan, Hongming; Chen, Shuqing; Fang, Yong","year":2022,"journal":"Frontiers in immunology, 13, 1000681","doi":"10.3389/fimmu.2022.1000681","pmid":"36248865","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Patients who received RFA before vaccination had a median progression-free survival of 4.42 months and overall survival of 20.18 months, compared to 2.82 months and 10.94 months in those who did not.","whyItMatters":"This research highlights a potential new strategy for improving cancer immunotherapy by combining local treatments with personalized vaccines, which could lead to better patient outcomes.","specificNumbers":"","methodology":"The study involved 28 cancer patients divided into two cohorts based on prior RFA treatment, and utilized mouse models to test the treatment's efficacy.","limitations":"The study's sample size was relatively small, and the results from mice may not fully translate to human patients."},{"rthcId":"RPEP-06501","title":"Current Trends and Applications of Food-derived Antihypertensive Peptides for the Management of Cardiovascular Disease.","authors":"Shukla, Pratik; Chopada, Keval; Sakure, Amar; Hati, Subrota","year":2022,"journal":"Protein and peptide letters, 29(5), 408-428","doi":"10.2174/0929866529666220106100225","pmid":"34994309","tags":[],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Food-derived peptides from diverse sources — milk, meat, fish, eggs, soy, rice, wheat, mushrooms, and pumpkins — can lower blood pressure through multiple mechanisms targeting the renin-angiotensin system (RAS). These peptides inhibit both renin and angiotensin-converting enzyme (ACE), the two key enzymes that raise blood pressure.\n\nBeyond enzyme inhibition, food-derived ACE inhibitory peptides also enhance nitric oxide production in blood vessel walls, promoting vasodilation (blood vessel relaxation). Additionally, they can block the interaction between angiotensin II and its receptor, providing a third mechanism for blood pressure reduction.\n\nThe review surveys the breadth of food sources containing antihypertensive peptides and their various applications for managing cardiovascular disease.","whyItMatters":"Hypertension affects over a billion people worldwide and is the leading modifiable risk factor for cardiovascular disease. While pharmaceutical ACE inhibitors are highly effective, food-derived peptides offer a potential complementary approach with fewer side effects. Understanding which foods naturally contain blood pressure-lowering peptides could inform dietary recommendations and functional food development for people with mild hypertension or those seeking to prevent it.","specificNumbers":"Multiple food sources surveyed · 3 mechanisms identified: renin inhibition, ACE inhibition, angiotensin II receptor blocking · Nitric oxide enhancement pathway documented","methodology":"This is a narrative review surveying published literature on food-derived antihypertensive peptides. It covers peptide sources (dairy, animal, plant, and other food proteins), mechanisms of action (renin inhibition, ACE inhibition, angiotensin II receptor blocking, nitric oxide enhancement), and applications for cardiovascular disease management.","limitations":"As a narrative review, it synthesizes existing literature without conducting meta-analysis or quantifying effect sizes. Most food-derived peptide research involves in vitro ACE inhibition assays or small clinical studies — large-scale human trials are limited. The blood pressure-lowering effects of food peptides are generally modest compared to pharmaceutical ACE inhibitors."},{"rthcId":"RPEP-06502","title":"Stable Gastric Pentadecapeptide BPC 157 as Useful Cytoprotective Peptide Therapy in the Heart Disturbances, Myocardial Infarction, Heart Failure, Pulmonary Hypertension, Arrhythmias, and Thrombosis Presentation.","authors":"Sikiric, Predrag; Udovicic, Mario; Barisic, Ivan; Balenovic, Diana; Zivanovic Posilovic, Gordana; Strinic, Dean; Uzun, Sandra; Sikiric, Suncana; Krezic, Ivan; Zizek, Helena; Yago, Haidi; Gojkovic, Slaven; Smoday, Ivan Maria; Kalogjera, Luka; Vranes, Hrvoje; Sola, Marija; Strbe, Sanja; Koprivanac, Antun; Premuzic Mestrovic, Ivica; Mestrovic, Tomislav; Pavic, Predrag; Skrtic, Anita; Blagaic, Alenka Boban; Lovric Bencic, Martina; Seiwerth, Sven","year":2022,"journal":"Biomedicines, 10(11)","doi":"10.3390/biomedicines10112696","pmid":"36359218","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BPC 157 demonstrated protective effects against heart disturbances, improving endothelial and thrombocyte function in rats.","whyItMatters":"Understanding how BPC 157 works could lead to new therapies for serious heart conditions, potentially improving patient outcomes.","specificNumbers":"","methodology":"The study involved vascular studies in rats to assess the effects of BPC 157 on heart disturbances and thrombosis.","limitations":"The study was conducted in rats, and results may not directly translate to humans; further research is needed."},{"rthcId":"RPEP-06503","title":"Prespecified and Integrated Subgroup Analyses from the RECONNECT Phase 3 Studies of Bremelanotide.","authors":"Simon, James A; Kingsberg, Sheryl A; Portman, David; Jordan, Robert; Lucas, Johna; Sadiq, Amama; Krop, Julie; Clayton, Anita H","year":2022,"journal":"Journal of women's health (2002), 31(3), 391-400","doi":"10.1089/jwh.2021.0225","pmid":"35230162","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Bremelanotide improved sexual desire and reduced distress in 1202 patients across most subgroups.","whyItMatters":"This research provides evidence that bremelanotide can effectively treat HSDD in various demographics, potentially improving quality of life for many women.","specificNumbers":"","methodology":"The study involved 1202 patients who self-administered bremelanotide 1.75 mg or a placebo for 24 weeks, with efficacy measured using specific sexual function scales.","limitations":"The study may not fully represent all women with HSDD, and results from clinical trials may not always translate to real-world settings."},{"rthcId":"RPEP-06504","title":"Wegovy (semaglutide): a new weight loss drug for chronic weight management.","authors":"Singh, Gurdeep; Krauthamer, Matthew; Bjalme-Evans, Meghan","year":2022,"journal":"Journal of investigative medicine : the official publication of the American Federation for Clinical Research, 70(1), 5-13","doi":"10.1136/jim-2021-001952","pmid":"34706925","tags":[],"studyType":"review","evidenceStrength":"strong","keyFinding":"This review summarizes weight loss results from three major semaglutide clinical trial programs: SUSTAIN (1.0 mg weekly injection for type 2 diabetes), PIONEER (oral semaglutide for type 2 diabetes), and STEP (2.4 mg weekly injection for obesity without diabetes). All three programs demonstrated that semaglutide — both injected and oral — produced superior weight loss compared to placebo and other antidiabetic medications. These results collectively supported the FDA approval of Wegovy (semaglutide 2.4 mg) as a dedicated weight loss medication.","whyItMatters":"This review documents the clinical evidence that transformed semaglutide from a diabetes drug into the first blockbuster GLP-1 weight loss medication. The STEP program in particular showed that a higher dose of semaglutide could produce substantial weight loss in people with obesity regardless of diabetes status, opening a massive new market for peptide-based therapeutics.","specificNumbers":"Semaglutide doses: 1.0 mg (diabetes) and 2.4 mg (obesity) weekly SC; oral formulation also studied · 3 trial programs: SUSTAIN, PIONEER, STEP · FDA-approved as Wegovy for chronic weight management","methodology":"Literature review summarizing data from the SUSTAIN, PIONEER, and STEP clinical trial programs. Trial data obtained from ClinicalTrials.gov and PubMed databases.","limitations":"This is a narrative literature review, not a systematic review or meta-analysis. Published shortly after Wegovy's approval, it captures early trial data but not longer-term real-world outcomes or the cardiovascular benefit data (SELECT trial) that came later. Does not discuss tirzepatide or other emerging competitors."},{"rthcId":"RPEP-06505","title":"Modulating the tachykinin: Role of substance P and neurokinin receptor expression in ocular surface disorders.","authors":"Singh, Rohan Bir; Naderi, Amirreza; Cho, Wonkyung; Ortiz, Gustavo; Musayeva, Aytan; Dohlman, Thomas H; Chen, Yihe; Ferrari, Giulio; Dana, Reza","year":2022,"journal":"The ocular surface, 25, 142-153","doi":"10.1016/j.jtos.2022.06.007","pmid":"35779793","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Substance P is essential for corneal wound healing and is involved in immune responses in ocular disorders.","whyItMatters":"Understanding the role of Substance P can lead to new treatments for common eye disorders. Targeting SP may improve healing and reduce inflammation in affected patients.","specificNumbers":"","methodology":"This is a review study summarizing existing research on Substance P and its receptor in ocular surface disorders.","limitations":"As a review, it synthesizes existing literature but does not present new experimental data."},{"rthcId":"RPEP-06506","title":"Systemic Candida albicans Infection in Mice Causes Endogenous Endophthalmitis via Breaching the Outer Blood-Retinal Barrier.","authors":"Singh, Sneha; Singh, Sukhvinder; Kumar, Ashok","year":2022,"journal":"Microbiology spectrum, 10(4), e0165822","doi":"10.1128/spectrum.01658-22","pmid":"35913202","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"C. albicans was detected in the eyes of mice at 3 days post-infection and persisted for up to 10 days, disrupting the blood-retinal barrier.","whyItMatters":"Understanding how C. albicans causes eye infections can lead to better treatments for patients suffering from fungal endophthalmitis, which can result in blindness.","specificNumbers":"","methodology":"The study used a murine model to investigate the effects of C. albicans infection on the blood-retinal barrier and inflammatory responses.","limitations":"The study was conducted in mice, and results may not directly translate to humans; further research is needed to confirm findings in human models."},{"rthcId":"RPEP-06507","title":"Expression of antimicrobial host defence peptides in the central nervous system during health and disease.","authors":"Smith, Katie J; Gwyer Findlay, Emily","year":2022,"journal":"Discovery immunology, 1(1), kyac003","doi":"10.1093/discim/kyac003","pmid":"38566904","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"HDP are expressed in the CNS of humans, rodents, birds, and fish, indicating a conserved protective role.","whyItMatters":"Understanding the role of HDP in the CNS could lead to new insights into immune responses in neurological diseases. This knowledge may help develop therapeutic strategies for conditions like infections and neurodegenerative diseases.","specificNumbers":"","methodology":"The study is a review of existing literature on HDP expression and function in the CNS across various species.","limitations":"The study is a review and does not present new experimental data; it relies on existing literature, which may vary in quality."},{"rthcId":"RPEP-06508","title":"Antibacterial and Antifungal Properties of a Novel Antimicrobial Peptide GK-19 and Its Application in Skin and Soft Tissue Infections Induced by MRSA or Candida albicans.","authors":"Song, Chenghua; Wen, Ruichao; Zhou, Jiaxuan; Zeng, Xiaoyan; Kou, Zi; Zhang, Jia; Wang, Tao; Chang, Pengkang; Lv, Yi; Wu, Rongqian","year":2022,"journal":"Pharmaceutics, 14(9)","doi":"10.3390/pharmaceutics14091937","pmid":"36145681","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GK-19 demonstrated broad-spectrum antimicrobial activity against five bacterial species (including Gram-positive and Gram-negative) and three fungal species by disrupting microbial cell membranes. Key advantages over the parent scorpion peptide AamAP1:\n\n- Negligible toxicity to mammalian cells (the original AamAP1 was strongly toxic)\n- Low hemolytic activity (does not destroy red blood cells)\n- High stability in blood plasma\n\nIn scalded mouse models with skin and soft tissue infections, GK-19 showed significant antimicrobial effects and improved wound healing when infections were induced by either MRSA (methicillin-resistant Staphylococcus aureus) or Candida albicans.","whyItMatters":"MRSA and Candida infections are major clinical challenges, particularly in burn patients and immunocompromised individuals. Antibiotic-resistant infections kill over 1.2 million people annually worldwide. GK-19 offers a dual advantage: it kills both bacteria and fungi (most antibiotics target only one or the other) through physical membrane disruption that pathogens cannot easily evolve resistance against. The successful reduction in toxicity from the parent scorpion peptide demonstrates that venom-derived peptides can be engineered into safe therapeutics.","specificNumbers":"","methodology":"Researchers designed GK-19 as a synthetic peptide based on the scorpion venom peptide AamAP1 and its derivatives. In vitro testing evaluated antimicrobial activity against five bacterial and three fungal species using standard susceptibility assays. Mechanism of action was confirmed through membrane disruption studies. Safety was assessed via mammalian cell toxicity assays, hemolysis testing, and plasma stability measurements. In vivo efficacy was evaluated using a scalded (burn wound) mouse model combined with skin and soft tissue infections induced by either MRSA or Candida albicans, measuring both microbial clearance and wound healing.","limitations":"While the mouse burn wound model is clinically relevant, it may not fully predict human responses. Specific MIC (minimum inhibitory concentration) values and comparative potency against standard antibiotics/antifungals are not detailed in the abstract. The study does not address manufacturing scale-up, cost, or formulation for clinical delivery. Long-term safety, pharmacokinetics, and potential for allergic reactions to a scorpion-derived peptide were not evaluated. The in vivo testing appears limited to topical application for skin infections — systemic use was not assessed."},{"rthcId":"RPEP-06509","title":"Digestion characteristics of quinoa, barley and mungbean proteins and the effects of their simulated gastrointestinal digests on CCK secretion in enteroendocrine STC-1 cells.","authors":"Song, Hongdong; Fu, Qiuyun; Huang, Kai; Zou, Zhiying; Chen, Limin; Chen, Hulin; Ge, Shaocheng; Wang, Jing; Guan, Xiao","year":2022,"journal":"Food & function, 13(11), 6233-6243","doi":"10.1039/d2fo00243d","pmid":"35587126","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Quinoa protein had 85.79% soluble nitrogen after digestion, while barley and mungbean had 74.98% and 64.14%, respectively.","whyItMatters":"Understanding how plant proteins affect digestion and hunger hormones can help in developing dietary strategies for weight management and health.","specificNumbers":"","methodology":"The study used an in vitro digestion model to analyze protein digestion and its effects on CCK secretion in STC-1 cells.","limitations":"The study was conducted in vitro, so results may not directly translate to human digestion."},{"rthcId":"RPEP-06510","title":"Intralesional injection of vitamin D in verruca vulgaris increases cathelicidin (LL37) expression; therapeutic and immunohistochemical study.","authors":"Sorour, Neveen E; Elesawy, Fatma M; Abdou, Asmaa G; Abdelazeem, Sara E; Akl, Essam M","year":2022,"journal":"The Journal of dermatological treatment, 33(1), 291-296","doi":"10.1080/09546634.2020.1750554","pmid":"32237947","tags":["ll-37","cathelicidin","antimicrobial-peptides"],"studyType":"interventional-clinical","evidenceStrength":"low-moderate","keyFinding":"Injecting vitamin D directly into common warts (verruca vulgaris) significantly increased expression of the antimicrobial peptide LL-37 (cathelicidin) in the skin (p=0.003). Of 20 patients treated, 40% showed complete wart clearance and 35% showed partial response. Warts that cleared completely had the highest LL-37 expression (p=0.022).\n\nAfter treatment, the skin also showed decreased epidermal thickness and reduced inflammatory cell density, indicating the immune response was shifting from chronic inflammation toward effective viral clearance driven by LL-37.","whyItMatters":"LL-37 is the body's primary antimicrobial peptide and plays a key role in fighting viral infections in the skin. This study provides a mechanistic explanation for why vitamin D injections work against warts — they boost the skin's natural LL-37 production, helping the immune system recognize and clear the HPV virus. This connects two major research areas: vitamin D's role in immunity and cathelicidin's antiviral properties.","specificNumbers":"n=20 patients · 10 healthy controls · 40% complete response · 35% partial response · 25% no response · LL-37 increase p=0.003 · Complete responders p=0.022 · Max 4 sessions every 2 weeks","methodology":"Twenty patients with multiple common warts received intralesional vitamin D3 injections every 2 weeks for up to 4 sessions or until warts cleared. Skin biopsies were taken before and after treatment and compared to samples from 10 healthy controls. LL-37 expression was assessed by immunohistochemistry. Histopathological changes in the epidermis and dermis were also evaluated.","limitations":"Small sample size (20 patients) limits generalizability. No placebo or sham injection control group — response could partly be due to the injection itself triggering local immunity. The study was not blinded. No long-term follow-up to assess recurrence rates."},{"rthcId":"RPEP-06511","title":"ISA101 and nivolumab for HPV-16+ cancer: updated clinical efficacy and immune correlates of response.","authors":"Sousa, Luana Guimaraes de; Rajapakshe, Kimal; Rodriguez Canales, Jaime; Chin, Renee L; Feng, Lei; Wang, Qi; Barrese, Tomas Z; Massarelli, Erminia; William, William; Johnson, Faye M; Ferrarotto, Renata; Wistuba, Ignacio; Coarfa, Cristian; Lee, Jack; Wang, Jing; Melief, Cornelis J M; Curran, Michael A; Glisson, Bonnie S","year":2022,"journal":"Journal for immunotherapy of cancer, 10(2)","doi":"10.1136/jitc-2021-004232","pmid":"35193933","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06512","title":"Effect of bremelanotide on body weight of obese women: Data from two phase 1 randomized controlled trials.","authors":"Spana, Carl; Jordan, Robert; Fischkoff, Steven","year":2022,"journal":"Diabetes, obesity & metabolism, 24(6), 1084-1093","doi":"10.1111/dom.14672","pmid":"35170192","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In Study A, bremelanotide subjects lost an average of 1.3 kg more than placebo; in Study B, those on twice-daily bremelanotide lost 1.7 kg compared to 0.9 kg for placebo.","whyItMatters":"These results indicate that bremelanotide could be a promising treatment for obesity, potentially aiding in weight management for women. Understanding its effects on appetite regulation may lead to better obesity interventions.","specificNumbers":"","methodology":"Two phase 1 randomized controlled trials were conducted, one with a 1:1 placebo comparison and another as a crossover trial with multiple treatment sequences.","limitations":"The study had a small sample size and was limited to premenopausal women, which may affect the generalizability of the results."},{"rthcId":"RPEP-06513","title":"TRP Channels: Recent Development in Translational Research and Potential Therapeutic Targets in Migraine.","authors":"Spekker, Eleonóra; Körtési, Tamás; Vécsei, László","year":2022,"journal":"International journal of molecular sciences, 24(1)","doi":"10.3390/ijms24010700","pmid":"36614146","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"TRP channels are implicated in migraine pain and symptoms like hyperalgesia and allodynia.","whyItMatters":"Understanding TRP channels could lead to novel therapeutic strategies for managing migraines, improving quality of life for many sufferers.","specificNumbers":"","methodology":"This is a review study discussing recent findings on TRP channels in migraine pathophysiology.","limitations":"As a review, it synthesizes existing research rather than presenting new experimental data."},{"rthcId":"RPEP-06514","title":"Mechanisms of RPE senescence and potential role of αB crystallin peptide as a senolytic agent in experimental AMD.","authors":"Sreekumar, Parameswaran G; Reddy, Srinivasa T; Hinton, David R; Kannan, Ram","year":2022,"journal":"Experimental eye research, 215, 108918","doi":"10.1016/j.exer.2021.108918","pmid":"34986369","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06515","title":"Stable Gastric Pentadecapeptide BPC 157 and Striated, Smooth, and Heart Muscle.","authors":"Staresinic, Mario; Japjec, Mladen; Vranes, Hrvoje; Prtoric, Andreja; Zizek, Helena; Krezic, Ivan; Gojkovic, Slaven; Smoday, Ivan Maria; Oroz, Katarina; Staresinic, Eva; Dretar, Vilim; Yago, Haidi; Milavic, Marija; Sikiric, Suncana; Lovric, Eva; Batelja Vuletic, Lovorka; Simeon, Paris; Dobric, Ivan; Strbe, Sanja; Kokot, Antonio; Vlainic, Josipa; Blagaic, Alenka Boban; Skrtic, Anita; Seiwerth, Sven; Sikiric, Predrag","year":2022,"journal":"Biomedicines, 10(12)","doi":"10.3390/biomedicines10123221","pmid":"36551977","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BPC 157 therapy effectively aids recovery from muscle and tendon injuries in rats.","whyItMatters":"Understanding BPC 157's healing properties could lead to new treatments for muscle injuries and related conditions. Its potential application in human therapy could improve recovery outcomes.","specificNumbers":"","methodology":"The study involved reviewing existing research on BPC 157's effects on muscle injuries in rat models.","limitations":"The study is based on animal models, and results may not directly translate to humans. Further clinical trials are needed."},{"rthcId":"RPEP-06516","title":"Mucoadhesive Electrospun Nanofiber-Based Hybrid System with Controlled and Unidirectional Release of Desmopressin.","authors":"Stie, Mai Bay; Gätke, Johan Ring; Chronakis, Ioannis S; Jacobsen, Jette; Nielsen, Hanne Mørck","year":2022,"journal":"International journal of molecular sciences, 23(3)","doi":"10.3390/ijms23031458","pmid":"35163377","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Approximately 80% of desmopressin was released within 45 minutes, and 90% was retained on the mucosa after 15 minutes.","whyItMatters":"This research provides a promising approach for delivering unstable therapeutic peptides, potentially improving their effectiveness and patient compliance.","specificNumbers":"","methodology":"The study developed a two-layered hybrid system combining peptide-loaded nanofibers and a saliva-repelling film, tested in vitro and ex vivo.","limitations":"The study was conducted in vitro and ex vivo, which may not fully replicate human conditions."},{"rthcId":"RPEP-06517","title":"Estrogenic regulation of reproduction and energy homeostasis by a triumvirate of hypothalamic arcuate neurons.","authors":"Stincic, Todd L; Kelly, Martin J","year":2022,"journal":"Journal of neuroendocrinology, 34(6), e13145","doi":"10.1111/jne.13145","pmid":"35581942","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies a 'triumvirate' of hypothalamic arcuate nucleus neurons — kisspeptin (Kiss1), pro-opiomelanocortin (POMC), and agouti-related peptide/neuropeptide Y (AgRP/NPY) — that arise from a common progenitor pool and are all regulated by estrogen (specifically 17β-estradiol).\n\nKiss1 neurons are the most sensitive to estrogen of the three populations and are critical for controlling gonadotropin-releasing hormone (GnRH) neurons, which drive the luteinizing hormone pulses and surges needed for ovulation. A key finding highlighted is that Kiss1 and POMC neurons collaborate to inhibit AgRP neurons, reducing food motivation. This provides a mechanistic explanation for how the brain prioritizes reproductive function over appetite during fertile periods — estrogen essentially tells the brain 'conditions are right for reproduction, reduce food-seeking behavior.'","whyItMatters":"Understanding how the brain links fertility and metabolism has major implications for reproductive disorders like PCOS and hypothalamic amenorrhea, eating disorders, and the metabolic effects of menopause. These same neuropeptide pathways (especially POMC/AgRP) are targets of obesity drugs, and kisspeptin is being investigated as a fertility treatment. This review reveals how estrogen ties all three systems together — knowledge essential for developing therapies that don't inadvertently disrupt the reproduction-metabolism balance.","specificNumbers":"","methodology":"This is a review article synthesizing recent research on estrogenic regulation of hypothalamic arcuate nucleus neurons. It integrates findings from electrophysiology, molecular signaling studies, and neuroanatomical tracing experiments to describe how estrogen's genomic and rapid membrane-initiated signaling cascades regulate the excitability of Kiss1, POMC, and AgRP neurons and their interactions.","limitations":"This is a review article that synthesizes existing research rather than presenting new data. Most of the underlying studies were conducted in rodent models, which may not perfectly reflect human hypothalamic function. The complexity of neuropeptide interactions makes it difficult to determine causality from correlation in many of the findings discussed. Human-specific differences in estrogen signaling and hypothalamic circuitry may exist."},{"rthcId":"RPEP-06518","title":"Thymosin beta-4 improves endothelial function and reparative potency of diabetic endothelial cells differentiated from patient induced pluripotent stem cells.","authors":"Su, Liping; Kong, Xiaocen; Loo, Szejie; Gao, Yu; Liu, Bingli; Su, Xiaofei; Dalan, Rinkoo; Ma, Jianhua; Ye, Lei","year":2022,"journal":"Stem cell research & therapy, 13(1), 13","doi":"10.1186/s13287-021-02687-x","pmid":"35012642","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Thymosin beta-4 at 600 ng/mL produced multiple improvements in diabetic endothelial cells:\n\n• Significantly upregulated AKT activity and Bcl-XL protein expression (pro-survival pathways)\n• Enhanced cell viability and proliferation\n• Reduced cellular senescence (aging)\n• Decreased secretion of endothelin-1 (a vasoconstrictor) and MMP-1 (a tissue-degrading enzyme)\n• Improved angiogenic (blood vessel-forming) potency when dia-hiPSC-ECs were used to treat ischemic limb disease in type 2 diabetic mice\n\nHowever, Tβ4 did NOT improve mitochondrial membrane potential, glycine homeostasis, or reduce ICAM-1 protein expression — showing its effects are specific to certain pathways rather than a universal fix for diabetic endothelial dysfunction.","whyItMatters":"Vascular complications are the leading cause of death and disability in diabetes — damaging the heart, kidneys, eyes, and limbs. Current treatments manage blood sugar but do little to directly repair damaged blood vessels. This study suggests thymosin beta-4 could restore the repair capacity of diabetic endothelial cells, potentially offering a peptide-based approach to treating diabetic vascular disease that addresses the underlying cell dysfunction rather than just managing symptoms.","specificNumbers":"","methodology":"Researchers created endothelial cells from induced pluripotent stem cells (iPSCs) derived from diabetic patients (dia-hiPSC-ECs), providing a human disease model. They treated these cells with thymosin beta-4 at 600 ng/mL and measured proliferation, senescence, cell survival, protein expression (ICAM-1, Bcl-XL, AKT), secretion (endothelin-1, MMP-1), and mitochondrial function in vitro. For in vivo testing, they transplanted Tβ4-treated diabetic endothelial cells into a mouse model of type 2 diabetes with ischemic limb disease to assess angiogenic repair potential.","limitations":"The in vitro work used iPSC-derived cells which, while patient-derived, may not perfectly replicate endothelial cells in a living body. The in vivo component used a mouse model of T2DM, which may not translate directly to human diabetic vascular disease. The study did not determine optimal dosing schedules, long-term effects, or address why Tβ4 failed to improve mitochondrial function and glycine homeostasis. No human clinical data was generated."},{"rthcId":"RPEP-06519","title":"Codelivery of 1α,25-Dihydroxyvitamin D3 and CYP24A1 Inhibitor VID400 by Nanofiber Dressings Promotes Endogenous Antimicrobial Peptide LL-37 Induction.","authors":"Su, Yajuan; Ganguli-Indra, Gitali; Bhattacharya, Nilika; Logan, Isabelle E; Indra, Arup K; Gombart, Adrian F; Wong, Shannon L; Xie, Jingwei","year":2022,"journal":"Molecular pharmaceutics, 19(3), 974-984","doi":"10.1021/acs.molpharmaceut.1c00944","pmid":"35179903","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The nanofiber dressings significantly increased hCAP18/LL-37 expression in wounds compared to free drugs.","whyItMatters":"Surgical site infections are a major concern in healthcare, and enhancing the body's natural defenses could lead to better patient outcomes. This innovative dressing could provide a new strategy for infection prevention.","specificNumbers":"","methodology":"The study involved creating nanofiber dressings that coencapsulated 1α,25-dihydroxyvitamin D3 and VID400, followed by testing their effects on gene expression in vitro and in vivo.","limitations":"The study primarily involved animal models, and further research is needed to confirm effectiveness in humans."},{"rthcId":"RPEP-06520","title":"Engineered Exosomes Containing Cathelicidin/LL-37 Exhibit Multiple Biological Functions.","authors":"Su, Yajuan; Sharma, Navatha Shree; John, Johnson V; Ganguli-Indra, Gitali; Indra, Arup K; Gombart, Adrian F; Xie, Jingwei","year":2022,"journal":"Advanced healthcare materials, 11(20), e2200849","doi":"10.1002/adhm.202200849","pmid":"35930707","tags":["cathelicidins","antimicrobial-peptides","peptide-delivery"],"studyType":"In Vitro Laboratory Study","evidenceStrength":"early-stage","keyFinding":"Researchers created exosomes (tiny cell-derived vesicles) loaded with high levels of the antimicrobial peptide LL-37 by treating immune cells with vitamin D3 and a CYP24A1 inhibitor. These engineered exosomes contained significantly more LL-37 than exosomes from untreated cells or genetically transfected cells.\n\nThe LL-37-loaded exosomes performed three functions simultaneously: they killed bacteria, promoted blood vessel formation (endothelial tube formation), and enhanced skin cell growth and migration. When embedded in electrospun nanofiber matrices for slow release, they became a multi-functional wound healing platform.","whyItMatters":"Wound infections are a major clinical problem, especially in chronic wounds and burns. Current approaches typically treat infection and promote healing separately. These engineered exosomes do both at once — killing bacteria while stimulating tissue repair — delivered from a degradable scaffold. The vitamin D connection is also notable, linking LL-37 production to a common nutritional deficiency.","specificNumbers":"Significantly more LL-37 than controls · kills bacteria · promotes endothelial tube formation · enhances skin cell proliferation and migration · delivered via electrospun nanofiber matrix","methodology":"Researchers treated monocytic (immune) cells with 1α,25-dihydroxyvitamin D3 and the CYP24A1 inhibitor VID400 to boost LL-37 production. They harvested exosomes from these treated cells, compared LL-37 content against untreated and transfected controls, and loaded them into electrospun nanofiber matrices for sustained release. Biological functions were tested in vitro: bacterial killing assays, endothelial tube formation assays, and skin cell proliferation/migration assays.","limitations":"All results are from in vitro (lab dish) experiments. No animal wound healing models or human testing was performed. The antibacterial spectrum was not detailed in the abstract. Manufacturing scalability and reproducibility are not addressed. Long-term stability of the exosome-loaded scaffolds is unknown."},{"rthcId":"RPEP-06521","title":"Screening and Molecular Mechanisms of Novel ACE-Inhibitory Peptides from Gracilariopsis lemaneiformis.","authors":"Su, Yongchang; Chen, Shicheng; Shen, Jiashen; Yi, Zhiwei; Liu, Shuji; Cai, Shuilin; Pan, Nan; Qiao, Kun; Chen, Xiaoting; Chen, Bei; Xu, Min; Yang, Suping; Liu, Zhiyu","year":2022,"journal":"International journal of molecular sciences, 23(23)","doi":"10.3390/ijms232314850","pmid":"36499176","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Peptide YIGNNPAKG reduced systolic blood pressure by approximately 23 mmHg.","whyItMatters":"Hypertension is a major health concern worldwide, and finding effective natural treatments can improve patient outcomes. These peptides could lead to new therapeutic options for managing high blood pressure.","specificNumbers":"","methodology":"The study involved virtual screening of peptides from seaweed hydrolysates, followed by synthesis and testing of selected peptides for ACE-inhibitory activity in hypertensive rats.","limitations":"The study was conducted in spontaneously hypertensive rats, and results may not directly translate to humans. Further clinical studies are needed."},{"rthcId":"RPEP-06522","title":"The Case for Early Use of Glucagon-like Peptide-1 Receptor Agonists in Obstructive Sleep Apnea Patients with Comorbid Diabetes and Metabolic Syndrome.","authors":"Sultana, Rizwana; Sissoho, Fatoumatta; Kaushik, Vinod P; Raji, Mukaila A","year":2022,"journal":"Life (Basel, Switzerland), 12(8)","doi":"10.3390/life12081222","pmid":"36013401","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1RAs can address multiple comorbidities in OSA patients, potentially reducing polypharmacy and improving quality of life.","whyItMatters":"This approach could significantly lower healthcare costs and improve patient outcomes by simplifying treatment regimens.","specificNumbers":"","methodology":"The study is a review of existing literature on the effects of GLP-1RAs in patients with OSA and related conditions.","limitations":"As a review, it does not provide new experimental data or clinical trials to support the recommendations."},{"rthcId":"RPEP-06523","title":"Activation of aryl hydrocarbon receptor ameliorates rosacea-like eruptions in mice and suppresses the TLR signaling pathway in LL-37-induced HaCaT cells.","authors":"Sun, Yan; Chen, LiangHong; Wang, HeXiao; Zhu, PeiYao; Jiang, ShiBin; Qi, RuiQun; Wu, Yan; Gao, XingHua","year":2022,"journal":"Toxicology and applied pharmacology, 451, 116189","doi":"10.1016/j.taap.2022.116189","pmid":"35926563","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Topical benvitimod (1% and 0.5%) reduced redness scores, redness areas, and dermal inflammatory cell infiltrates in LL-37-induced rosacea-like eruptions in BALB/c mice. In both the mouse model and LL-37-treated HaCaT cells, AhR activation decreased elevated TLR2 expression and suppressed four inflammatory chemokines: CCL5, CXCL9, CXCL10, and CXCL11. Over-expressing TLR2 in HaCaT cells further enhanced chemokine release, confirming TLR2 as the key pathway. Benvitimod (10 μM) reduced gene expression at 8 hours and protein expression at 24 hours in LL-37-treated cells.","whyItMatters":"Rosacea affects over 400 million people worldwide and current treatments have limited efficacy. Understanding that LL-37 — an endogenous antimicrobial peptide — drives rosacea through TLR2 signaling provides a specific therapeutic target. This study shows AhR activation can block this peptide-driven inflammatory cascade, offering a mechanistically targeted treatment approach.","specificNumbers":"","methodology":"Female BALB/c mice received twice-daily intradermal LL-37 injections for 2 days to induce rosacea-like eruptions, then topical benvitimod (AhR agonist) at 0.5% or 1% for 3 days. Redness scores, areas, and histological inflammation were assessed. In vitro, HaCaT keratinocytes were treated with LL-37 and benvitimod, with TLR2 overexpression via lentivirus. Inflammatory markers (TLR2, CCL5, CXCL9, CXCL10, CXCL11) were measured by qRT-PCR, Western blot, and ELISA.","limitations":"The LL-37 injection model creates acute rosacea-like symptoms that may not fully replicate the chronic nature of human rosacea. The study duration was very short (3 days of treatment). HaCaT cells are an immortalized keratinocyte line that may not perfectly represent primary skin cells. The AhR pathway has multiple effects beyond TLR suppression that weren't fully characterized. No human rosacea patients were studied. The relationship between LL-37 levels and specific rosacea subtypes was not addressed."},{"rthcId":"RPEP-06524","title":"Bioinspired supramolecular nanofiber hydrogel through self-assembly of biphenyl-tripeptide for tissue engineering.","authors":"Sun, Yong; Li, Xing; Zhao, Mingda; Chen, Yafang; Xu, Yang; Wang, Kefeng; Bian, Shaoquan; Jiang, Qing; Fan, Yujiang; Zhang, Xingdong","year":2022,"journal":"Bioactive materials, 8, 396-408","doi":"10.1016/j.bioactmat.2021.05.054","pmid":"34541409","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Biphenyl-tripeptide molecules self-assembled into nanofiber hydrogels at ultra-low concentrations (about 0.27 wt%) with mechanical strength ranging from 0.7 to 13.8 kPa. The strongest variant (BPAA-AFF) formed 10 nm nanofibers with a storage modulus of 13.8 kPa and a morphology resembling natural extracellular matrix.\n\nThese hydrogels demonstrated excellent biocompatibility, supporting cell adhesion and proliferation. When tested with cartilage cells, they specifically enhanced the expression of cartilage-related genes and promoted cartilage matrix production, suggesting strong potential for cartilage tissue engineering.","whyItMatters":"Regenerative medicine needs scaffold materials that mimic the body's natural tissue structure. These ultra-simple peptide hydrogels — made from just three amino acids with a biphenyl group — self-assemble into structures that closely resemble natural extracellular matrix at very low concentrations. Their ability to specifically promote cartilage cell behavior makes them promising candidates for cartilage repair, a major unmet clinical need.","specificNumbers":"0.27 wt% concentration · 0.7–13.8 kPa mechanical range · 13.8 kPa top storage modulus · 10 nm nanofiber diameter · Enhanced chondrogenic gene expression","methodology":"Researchers designed biphenyl-tripeptide sequences with different C-terminal amino acid arrangements and tested their self-assembly properties. They used molecular dynamics simulations to understand assembly at the atomic level, rheology to measure mechanical properties, and spectroscopy to analyze molecular interactions. Biocompatibility was tested with L929 cells, and cartilage-specific performance was evaluated using chondrocytes measuring gene expression and matrix secretion.","limitations":"All testing was performed in laboratory conditions (in vitro). The hydrogels have not been tested in living organisms, so it is unknown how they would perform in actual tissue repair scenarios including immune responses, degradation rates, and integration with surrounding tissue. Long-term stability and safety remain uncharacterized."},{"rthcId":"RPEP-06525","title":"Binding Domain Characterization of Growth Hormone Secretagogue Receptor.","authors":"Sun, Yuxiang; Ye, Xiangcang; Kennedy, Hilda; Smith, Alexander G A; Smith, Roy G","year":2022,"journal":"Journal of translational internal medicine, 10(2), 146-155","doi":"10.2478/jtim-2022-0033","pmid":"35959447","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Synthetic ligands MK-0677 and GHS-25 had higher GH secretagogue activity than ghrelin, with activity abolished in GHS-R knockout mice.","whyItMatters":"Understanding GHS-R interactions can lead to the development of more effective drugs for growth-related conditions. This research highlights potential targets for designing new GHS-R agonists and antagonists.","specificNumbers":"","methodology":"The study used radiolabeled ligand-binding assays, growth hormone release assays, and aequorin-based calcium response measurements, along with chimeric receptor analysis and site-directed mutagenesis.","limitations":"The study was conducted in vitro and in knockout mice, which may not fully represent human physiology."},{"rthcId":"RPEP-06526","title":"Incretin based therapy and pancreatic cancer: Realising the reality.","authors":"Suryadevara, Varun; Roy, Ayan; Sahoo, Jayaprakash; Kamalanathan, Sadishkumar; Naik, Dukhabandhu; Mohan, Pazhanivel; Kalayarasan, Raja","year":2022,"journal":"World journal of gastroenterology, 28(25), 2881-2889","doi":"10.3748/wjg.v28.i25.2881","pmid":"35978867","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Clinical trials and population-based studies have established safety regarding pancreatic carcinoma for incretin-based therapies. However, animal models have inconsistently shown low-grade chronic pancreatitis with these medications, and some human studies have reported acute pancreatitis. Since chronic pancreatitis is a known risk factor for pancreatic cancer, the pathophysiological pathway from drug-induced inflammation to cancer remains a theoretical concern even though epidemiological evidence has not confirmed it.","whyItMatters":"GLP-1 receptor agonists are now prescribed to tens of millions of people worldwide for diabetes and obesity. Any link to pancreatic cancer — even theoretical — has enormous public health implications. This review provides reassurance from clinical data while honestly acknowledging the biological plausibility of the concern, helping clinicians and patients make informed decisions.","specificNumbers":"","methodology":"Narrative literature review examining existing clinical trial data, population-based studies, and animal model research on the relationship between incretin-based therapies (GLP-1 receptor agonists and DPP-4 inhibitors) and pancreatic cancer risk.","limitations":"This is a narrative review, not a systematic review or meta-analysis, so the literature search and inclusion criteria may not be comprehensive. The review acknowledges that clinical trials may have insufficient follow-up duration to detect a cancer signal, as pancreatic cancer develops over many years. Animal model findings have been inconsistent and may not translate to humans. Publication bias could affect the available evidence."},{"rthcId":"RPEP-06527","title":"The Role of Ghrelin/GHS-R1A Signaling in Nonalcohol Drug Addictions.","authors":"Sustkova-Fiserova, Magdalena; Charalambous, Chrysostomos; Khryakova, Anna; Certilina, Alina; Lapka, Marek; Šlamberová, Romana","year":2022,"journal":"International journal of molecular sciences, 23(2)","doi":"10.3390/ijms23020761","pmid":"35054944","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Ghrelin's/GHS-R1A's involvement is significant in nonalcohol drug addiction, as indicated by preclinical studies.","whyItMatters":"Understanding ghrelin's role in addiction could lead to more effective treatments for drug dependence. This is crucial given the limitations of current therapies.","specificNumbers":"","methodology":"The study is a review of existing preclinical and clinical research on ghrelin signaling and addiction.","limitations":"The review primarily focuses on preclinical studies, which may not fully translate to human conditions."},{"rthcId":"RPEP-06528","title":"Role of antimicrobial peptides in atopic dermatitis.","authors":"Suwanchote, Supaporn; Waitayangkoon, Palapun; Chancheewa, Bussabong; Inthanachai, Thananya; Niwetbowornchai, Nattarika; Edwards, Steven W; Virakul, Sita; Thammahong, Arsa; Kiatsurayanon, Chanisa; Rerknimitr, Pawinee; Chiewchengchol, Direkrit","year":2022,"journal":"International journal of dermatology, 61(5), 532-540","doi":"10.1111/ijd.15814","pmid":"34432296","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"HDPs are dysregulated in the skin of patients with atopic dermatitis, affecting disease severity.","whyItMatters":"Understanding the role of antimicrobial peptides could lead to better predictions of disease severity and new treatment options for atopic dermatitis.","specificNumbers":"","methodology":"This is a review study analyzing existing research on antimicrobial peptides in relation to atopic dermatitis.","limitations":"As a review, it summarizes existing literature but does not present new experimental data."},{"rthcId":"RPEP-06529","title":"Characterization of the membrane penetration-enhancing peptide S19 derived from human syncytin-1 for the intracellular delivery of TAT-fused proteins.","authors":"Suzuki, Mayuko; Iwaki, Kouta; Kikuchi, Moeki; Fujiwara, Kei; Doi, Nobuhide","year":2022,"journal":"Biochemical and biophysical research communications, 586, 63-67","doi":"10.1016/j.bbrc.2021.11.065","pmid":"34826702","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"S19 enhances endosomal escape efficiency of TAT-fused proteins, with specific amino acids crucial for uptake.","whyItMatters":"Improving intracellular delivery of therapeutic proteins could enhance treatments for various diseases. Understanding peptide interactions with cell membranes is crucial for developing effective drug delivery systems.","specificNumbers":"","methodology":"The study involved Ala-scanning mutagenesis of the S19 peptide and structural analysis of mutated S19-TAT peptides in liposome models.","limitations":"The study primarily focuses on in vitro models, which may not fully replicate in vivo conditions."},{"rthcId":"RPEP-06530","title":"Expression of chemerin in intestinal mucosa of calves with comparable expression level with other antimicrobial proteins.","authors":"Suzuki, Yutaka; Kubota, Kanako; Haga, Satoshi; Hayashi, Hideaki; Oishi, Mutsumi; Miura, Hiroto; Roh, Sanggun; Koike, Satoshi; Kobayashi, Yasuo","year":2022,"journal":"Animal science journal = Nihon chikusan Gakkaiho, 93(1), e13750","doi":"10.1111/asj.13750","pmid":"35774014","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Chemerin was highly expressed in the duodenum, jejunum, and ileum, with RARRES2 levels higher than other AMPs in the duodenum.","whyItMatters":"Understanding chemerin's role in calf immunity could help improve health management in livestock, particularly in preventing infections.","specificNumbers":"","methodology":"The study used immunohistochemistry to analyze chemerin expression in the gastrointestinal tract of calves.","limitations":"The study focused only on calves, and results may not directly apply to other species or older animals."},{"rthcId":"RPEP-06531","title":"Redesigning of Cell-Penetrating Peptides to Improve Their Efficacy as a Drug Delivery System.","authors":"Szabó, Ildikó; Yousef, Mo'ath; Soltész, Dóra; Bató, Csaba; Mező, Gábor; Bánóczi, Zoltán","year":2022,"journal":"Pharmaceutics, 14(5)","doi":"10.3390/pharmaceutics14050907","pmid":"35631493","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Modifications to CPPs can significantly enhance their internalization and targeting.","whyItMatters":"Improving CPPs could lead to more effective drug delivery systems, potentially enhancing treatment outcomes. This research could pave the way for better therapies using these peptides.","specificNumbers":"","methodology":"The study is a review of existing literature on CPP modifications and their effects.","limitations":"As a review, it does not provide original experimental data or direct comparisons of peptide efficacy."},{"rthcId":"RPEP-06532","title":"Tirzepatide: A novel, first-in-class, dual GIP/GLP-1 receptor agonist.","authors":"Tall Bull, Shasta; Nuffer, Wesley; Trujillo, Jennifer M","year":2022,"journal":"Journal of diabetes and its complications, 36(12), 108332","doi":"10.1016/j.jdiacomp.2022.108332","pmid":"36375235","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tirzepatide significantly lowers glycated hemoglobin and promotes weight loss.","whyItMatters":"Tirzepatide offers a new option for managing type 2 diabetes, particularly for patients needing effective glucose control with minimal hypoglycemia risk. Its potential inclusion in treatment guidelines could improve patient outcomes.","specificNumbers":"","methodology":"The study reviews data from phase III clinical trials (SURPASS-1 to SURPASS-5) comparing tirzepatide to placebo and other diabetes medications.","limitations":"The review relies on clinical trial data, and long-term safety and efficacy in diverse populations need further investigation."},{"rthcId":"RPEP-06533","title":"Novel angiotensin I-converting enzyme (ACE) inhibitory peptides from walnut protein isolate: Separation, identification and molecular docking study.","authors":"Tang, Hengkuan; Wang, Chen; Cao, Shinuo; Wang, Fengjun","year":2022,"journal":"Journal of food biochemistry, 46(12), e14411","doi":"10.1111/jfbc.14411","pmid":"36121201","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Four ACE inhibitory peptides were identified, with PPKP having the highest activity (IC50 = 89 μmol/L).","whyItMatters":"These findings could lead to the development of new dietary approaches to manage hypertension, a major health concern globally. Additionally, utilizing walnut meal can help reduce food waste and environmental impact.","specificNumbers":"","methodology":"The study involved hydrolyzing walnut protein isolate, purifying peptides using ultrafiltration and chromatography, and identifying them through HPLC-MS/MS.","limitations":"The study primarily focuses on in vitro results, and further research is needed to confirm effectiveness in human subjects."},{"rthcId":"RPEP-06534","title":"The progress of peptide vaccine clinical trials in gynecologic oncology.","authors":"Tang, Mi; Cai, Jiang-Hui; Diao, Hao-Yang; Guo, Wen-Mei; Yang, Xiao; Xing, ShaSha","year":2022,"journal":"Human vaccines & immunotherapeutics, 18(5), 2062982","doi":"10.1080/21645515.2022.2062982","pmid":"35687860","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"No peptide vaccine has been licensed for gynecologic oncology as of January 2022.","whyItMatters":"Understanding the progress of peptide vaccines can lead to improved treatments for gynecologic cancers. This research highlights the need for continued innovation in immunotherapy.","specificNumbers":"","methodology":"The study is a review of clinical trials registered on ClinicalTrials.gov up to January 1, 2022.","limitations":"The review does not provide new clinical trial data or outcomes, focusing instead on existing studies."},{"rthcId":"RPEP-06535","title":"Substance P modulates BMSCs migration for tissue repair through NK-1R/CXCR4/p-Akt signal activation.","authors":"Tao, Ran; Qu, Zhan; Zhang, Ke; Chen, Jie; Wang, Xinyu; Deng, Youming","year":2022,"journal":"Molecular biology reports, 49(3), 2227-2236","doi":"10.1007/s11033-021-07044-y","pmid":"35034285","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Substance P increased BMSC migration and wound healing, linked to CXCR4 and p-Akt activation.","whyItMatters":"Understanding how SP enhances stem cell migration could lead to new treatments for improving wound healing and tissue repair in clinical settings.","specificNumbers":"","methodology":"The study utilized Western blot and q-PCR assays to analyze signaling pathways and employed a skin-injury animal model to assess tissue repair.","limitations":"The study primarily used animal models, which may not fully represent human responses."},{"rthcId":"RPEP-06536","title":"CRISPR-Cas9 editing of the arginine-vasopressin V1a receptor produces paradoxical changes in social behavior in Syrian hamsters.","authors":"Taylor, Jack H; Walton, James C; McCann, Katharine E; Norvelle, Alisa; Liu, Qian; Vander Velden, Jacob W; Borland, Johnathan M; Hart, Michael; Jin, Chengliu; Huhman, Kim L; Cox, Daniel N; Albers, H Elliott","year":2022,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 119(19), e2121037119","doi":"10.1073/pnas.2121037119","pmid":"35512092","tags":["vasopressin","social-behavior"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"When researchers used CRISPR gene editing to completely knock out the vasopressin V1a receptor in Syrian hamsters, the results were the opposite of what decades of research predicted. Instead of becoming less social and less aggressive, the knockout hamsters were substantially more social (more flank-marking communication) and more aggressive toward same-sex peers than normal hamsters.\n\nAdditionally, the typical sex differences in aggression disappeared — both male and female knockouts showed elevated aggression. The knockout was confirmed to be complete: no V1a receptor binding was detected anywhere in the brain, and the animals showed no response to vasopressin or V1a-specific drugs.\n\nThese paradoxical findings suggest that the vasopressin V1a receptor may actually inhibit social behavior rather than promote it — flipping the long-held assumption about how this peptide system works.","whyItMatters":"Vasopressin has been considered a key driver of social bonding and aggression for decades, with the V1a receptor assumed to promote these behaviors. This study fundamentally challenges that narrative by showing the complete opposite effect when the receptor is eliminated. If vasopressin V1a signaling is actually inhibitory rather than permissive for social behavior, it could reshape how we think about peptide-based treatments for social disorders like autism.","specificNumbers":"Complete Avpr1a knockout confirmed · Higher flank marking in KO vs WT · Both sexes showed increased aggression · 0 functional V1a receptors detected","methodology":"Researchers used CRISPR-Cas9 gene editing via pronuclear microinjection in Syrian hamsters to create a stable knockout line lacking functional vasopressin V1a receptors. They confirmed the knockout through autoradiographic binding (showing zero V1a binding in brain), behavioral insensitivity to injected vasopressin, and absent blood pressure response to a V1a agonist. Knockout and wild-type littermates were then compared on social communication (flank marking) and same-sex aggression.","limitations":"Results are from Syrian hamsters, which may not translate directly to other species or humans. The complete receptor knockout is a more extreme manipulation than natural variation in receptor expression. Compensatory changes in other receptor systems during development could contribute to the paradoxical results. The study does not identify the mechanism behind the unexpected behavioral changes."},{"rthcId":"RPEP-06537","title":"The Elastin Receptor Complex: An Emerging Therapeutic Target Against Age-Related Vascular Diseases.","authors":"Tembely, Dignê; Henry, Aubéri; Vanalderwiert, Laetitia; Toussaint, Kevin; Bennasroune, Amar; Blaise, Sébastien; Sartelet, Hervé; Jaisson, Stéphane; Galés, Céline; Martiny, Laurent; Duca, Laurent; Romier-Crouzet, Béatrice; Maurice, Pascal","year":2022,"journal":"Frontiers in endocrinology, 13, 815356","doi":"10.3389/fendo.2022.815356","pmid":"35222273","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06538","title":"Probing for peptidic drugs (2-10 kDa) in doping control blood samples.","authors":"Thomas, Andreas; Thilmany, Sam; Hofmann, Amelie; Thevis, Mario","year":2022,"journal":"Analytical science advances, 3(7-8), 235-243","doi":"10.1002/ansa.202200027","pmid":"38716080","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The method successfully detected multiple peptides in blood samples, fulfilling WADA requirements.","whyItMatters":"This research is significant for improving doping control in sports, ensuring fair competition. It provides a reliable method for detecting banned substances that are increasingly used by athletes.","specificNumbers":"","methodology":"The study employed liquid chromatography coupled with high-resolution mass spectrometry for peptide analysis in blood samples.","limitations":"The study primarily focuses on blood samples and may not address urine testing or other sample types."},{"rthcId":"RPEP-06539","title":"Thymosin β4 Suppresses LPS-Induced Murine Lung Fibrosis by Attenuating Oxidative Injury and Alleviating Inflammation.","authors":"Tian, Zhen; Yao, Naijuan; Wang, Fei; Ruan, Litao","year":2022,"journal":"Inflammation, 45(1), 59-73","doi":"10.1007/s10753-021-01528-6","pmid":"34414534","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tβ4 significantly reduced LPS-induced lung injury, inflammation, and fibrosis in mice.","whyItMatters":"Understanding how Tβ4 works could lead to new treatments for pulmonary fibrosis, a serious lung condition. This research highlights the potential of Tβ4 in mitigating lung damage.","specificNumbers":"","methodology":"The study used real-time PCR, immunohistochemistry, and western blotting to assess Tβ4 expression and evaluated the effects of AAV-Tβ4 on lung injury in mice.","limitations":"The study was conducted in mice, and results may not directly translate to humans. Further research is needed to explore long-term effects and safety."},{"rthcId":"RPEP-06540","title":"Tricyclic cell-penetrating peptides for efficient delivery of functional antibodies into cancer cells.","authors":"Tietz, Ole; Cortezon-Tamarit, Fernando; Chalk, Rod; Able, Sarah; Vallis, Katherine A","year":2022,"journal":"Nature chemistry, 14(3), 284-293","doi":"10.1038/s41557-021-00866-0","pmid":"35145246","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A tricyclic Tat construct allows delivery of antibodies at concentrations as low as 1 μM.","whyItMatters":"This research addresses a significant challenge in cancer treatment by enabling the delivery of therapeutic antibodies to previously inaccessible targets. It opens new avenues for targeting complex disease pathways.","specificNumbers":"","methodology":"The study involved designing and testing various trimeric cell-penetrating peptides for their ability to deliver antibodies into live cancer cells.","limitations":"The study primarily focuses on in vitro models, and further research is needed to confirm effectiveness in vivo."},{"rthcId":"RPEP-06541","title":"Tunable Self-Assembled Peptide Hydrogel Sensor for Pharma Cold Supply Chain.","authors":"Tikhonova, Tatiana N; Cohen-Gerassi, Dana; Arnon, Zohar A; Efremov, Yuri; Timashev, Peter; Adler-Abramovich, Lihi; Shirshin, Evgeny A","year":2022,"journal":"ACS applied materials & interfaces, 14(50), 55392-55401","doi":"10.1021/acsami.2c17609","pmid":"36475602","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Self-assembled peptide hydrogels were successfully used to build a defrost sensor that uses turbidity (cloudiness) changes as a temperature indicator. The sensor irreversibly records whether a product has been thawed, preventing tampering or resetting.\n\nBy studying the gelation kinetics under different conditions, the researchers identified distinct stages of structural transitions in the hydrogel, allowing them to tune the sensor's response to specific temperature ranges and detection timeframes. The sensor can be stored at room temperature for extended periods before activation.","whyItMatters":"The pharmaceutical cold chain is a major logistical challenge — billions of dollars in medications are lost annually due to temperature excursions during transport. Current electronic temperature monitors can be expensive and complex. A simple, low-cost, peptide-based visual sensor that permanently records thawing events could make cold chain monitoring more accessible and tamper-proof, particularly in resource-limited settings.","specificNumbers":"","methodology":"The researchers constructed hydrogels from self-assembling peptides and measured their turbidity (light transmission) as a function of temperature changes. They systematically studied gelation kinetics — how quickly and under what conditions the peptides form gel networks — to map structural transitions at different temperatures. This allowed them to tune the sensor properties for specific cold chain requirements. The mechanical and optical properties of the hydrogels were characterized to establish reliable detection thresholds.","limitations":"The study is a proof-of-concept and does not include real-world field testing during actual pharmaceutical shipments. Long-term stability under variable environmental conditions (humidity, light exposure, vibration) was not assessed. Specific temperature accuracy and sensitivity compared to existing electronic sensors were not benchmarked. Scale-up manufacturing feasibility and cost analysis were not addressed."},{"rthcId":"RPEP-06542","title":"Host Defense Peptides at the Ocular Surface: Roles in Health and Major Diseases, and Therapeutic Potentials.","authors":"Ting, Darren Shu Jeng; Mohammed, Imran; Lakshminarayanan, Rajamani; Beuerman, Roger W; Dua, Harminder S","year":2022,"journal":"Frontiers in medicine, 9, 835843","doi":"10.3389/fmed.2022.835843","pmid":"35783647","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"HDPs are involved in multiple ocular conditions and show promise for new treatments.","whyItMatters":"Understanding HDPs can lead to new therapeutic strategies for common eye diseases, improving patient outcomes.","specificNumbers":"","methodology":"This is a review study that summarizes existing research on host defense peptides at the ocular surface.","limitations":"As a review, it may not include the most recent studies or experimental data."},{"rthcId":"RPEP-06543","title":"CLIPSing Melanotan-II to Discover Multiple Functionally Selective hMCR Agonists.","authors":"Tomassi, Stefano; Dimmito, Marilisa Pia; Cai, Minying; D'Aniello, Antonia; Del Bene, Alessandra; Messere, Anna; Liu, Zekun; Zhu, Tingyi; Hruby, Victor J; Stefanucci, Azzurra; Cosconati, Sandro; Mollica, Adriano; Di Maro, Salvatore","year":2022,"journal":"Journal of medicinal chemistry, 65(5), 4007-4017","doi":"10.1021/acs.jmedchem.1c01848","pmid":"35188390","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Compound 5 showed remarkable functional selectivity toward the hMC1R receptor.","whyItMatters":"Improving selectivity of receptor agonists can lead to better therapeutic options with fewer side effects. This research contributes to the development of targeted treatments for conditions influenced by melanocortin receptors.","specificNumbers":"","methodology":"The study utilized a Chemical Linkage of Peptide onto Scaffolds strategy to modify melanotan II and assessed binding affinities through molecular dynamics simulations.","limitations":"The study primarily focuses on in vitro findings, which may not fully translate to in vivo results or human applications."},{"rthcId":"RPEP-06544","title":"The association of biomarkers with pain and function in acute and subacute low back pain: a secondary analysis of an RCT.","authors":"Tonelli Enrico, Valerio; Schneider, Michael; Haas, Mitchell; Vo, Nam; Huang, Wan; McFarland, Christine; Weber, Nick; Sowa, Gwendolyn","year":2022,"journal":"BMC musculoskeletal disorders, 23(1), 1059","doi":"10.1186/s12891-022-06027-9","pmid":"36471334","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Four biomarkers showed significant associations with pain levels: vitamin D (r = -0.32, p = 0.002) and C-reactive protein (r = 0.37, p = 0.001) among others.","whyItMatters":"Understanding the relationship between biomarkers and pain can help tailor treatments for low back pain, potentially improving patient outcomes.","specificNumbers":"","methodology":"The study analyzed blood samples from 90 participants in a randomized controlled trial, correlating biomarker levels with pain and disability outcomes.","limitations":"The study is limited by its small sample size and the fact that it only examines associations, not causation."},{"rthcId":"RPEP-06545","title":"Female fertility does not require Bmal1 in suprachiasmatic nucleus neurons expressing arginine vasopressin, vasoactive intestinal peptide, or neuromedin-S.","authors":"Tonsfeldt, Karen J; Cui, Laura J; Lee, Jinkwon; Walbeek, Thijs J; Brusman, Liza E; Jin, Ye; Mieda, Michihiro; Gorman, Michael R; Mellon, Pamela L","year":2022,"journal":"Frontiers in endocrinology, 13, 956169","doi":"10.3389/fendo.2022.956169","pmid":"35992114","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Female mice lacking Bmal1 in AVP, VIP, or NMS neurons showed normal estrus cycles and LH surges.","whyItMatters":"Understanding the relationship between circadian rhythms and fertility can help in addressing reproductive issues in females. This research challenges previous assumptions about the role of Bmal1 in reproductive health.","specificNumbers":"","methodology":"The study used Cre/Lox technology to create conditional knockouts of Bmal1 in specific neuron populations of mice.","limitations":"The study was conducted in mice, and results may not directly translate to humans. Additionally, it focused only on specific neuron populations."},{"rthcId":"RPEP-06546","title":"Dextrose Prolotherapy for Symptomatic Grade IV Knee Osteoarthritis: A Pilot Study of Early and Longer-Term Analgesia and Pain-Specific Cytokine Concentrations.","authors":"Topol, Gastón Andrés; Pestalardo, Ines Guerrero; Reeves, Kenneth Dean; Elias, Fernando; Steinmetz, Neven J; Cheng, An-Lin; Rabago, David","year":2022,"journal":"Clinics and practice, 12(6), 926-938","doi":"10.3390/clinpract12060097","pmid":"36412676","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Dextrose injections resulted in a 111% increase in synovial-fluid substance P at one week and a 65% decrease in neuropeptide Y at three months.","whyItMatters":"This research highlights a potential new treatment for chronic knee pain, which could improve quality of life for those suffering from osteoarthritis.","specificNumbers":"","methodology":"Participants underwent synovial-fluid aspiration followed by dextrose or placebo injections, with assessments of pain and neurocytokine levels over nine months.","limitations":"The study had a small sample size and lacked a long-term follow-up beyond nine months."},{"rthcId":"RPEP-06547","title":"Development of a rapid, simple, and sensitive point-of-care technology platform utilizing ternary NanoLuc.","authors":"Torio, Emily A; Ressler, Valerie T; Kincaid, Virginia A; Hurst, Robin; Hall, Mary P; Encell, Lance P; Zimmerman, Kristopher; Forsyth, Stuart K; Rehrauer, William M; Accola, Molly A; Hsu, Chia-Chang; Machleidt, Thomas; Dart, Melanie L","year":2022,"journal":"Frontiers in microbiology, 13, 970233","doi":"10.3389/fmicb.2022.970233","pmid":"36386626","tags":["peptide-diagnostics","biosensors"],"studyType":"experimental","evidenceStrength":"moderate","keyFinding":"A split-peptide reporter system using ternary NanoLuc luciferase enables rapid, simple, and sensitive point-of-care diagnostics. Two small reporter peptides are attached to analyte-specific binding molecules. When both peptides bind their target, they come into proximity and reconstitute with a larger polypeptide to produce a bright bioluminescent signal — effectively turning target detection into a visible light signal.\n\nThe platform was demonstrated with two SARS-CoV-2 applications: detecting the N-antigen (active infection) and detecting anti-SARS-CoV-2 antibodies (immunity status). The system was lyophilized (freeze-dried) into a shelf-stable, all-in-one format that requires only adding the sample and reading with a handheld device.","whyItMatters":"Current diagnostic tests like ELISAs require trained technicians, complex equipment, and hours of processing. This peptide-based split reporter turns detection into a simple 'add sample and read' format that works with a handheld device. The modular design means the same platform can be adapted to detect virtually any target — from viruses to biomarkers — making it potentially transformative for rapid diagnostics in clinics, pharmacies, and homes.","specificNumbers":"ternary split system (2 peptides + 1 polypeptide) · lyophilized shelf-stable · add-and-read format · 2 SARS-CoV-2 applications validated · handheld luminometer readout","methodology":"Developed an optimized ternary split-NanoLuc luciferase system with two reporter peptides fused or conjugated to analyte-specific affinity reagents. Validated in two SARS-CoV-2 model systems using chemically conjugated and genetically fused configurations. Lyophilized the system for shelf stability and tested in complex sample matrices.","limitations":"Demonstrated only with SARS-CoV-2 targets — sensitivity and specificity for other analytes need separate validation. The technology requires a handheld luminometer, which adds cost compared to simple lateral flow tests. Performance in real-world clinical samples across diverse populations needs further evaluation."},{"rthcId":"RPEP-06548","title":"Identification of a Multi-Component Formulation for Intestinal Delivery of a GLP-1/Glucagon Co-agonist Peptide.","authors":"Tran, Huyen; Patel, Phenil J; Aburub, Aktham; Sperry, Andrea; Estwick, Selina; ElSayed, Mohamed E H; -Mannan, Amita Datta","year":2022,"journal":"Pharmaceutical research, 39(10), 2555-2567","doi":"10.1007/s11095-022-03372-1","pmid":"36050547","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The combination of C10 and SBTI increased peptide exposure 5-10 times compared to using C10 alone.","whyItMatters":"Improving the oral delivery of peptide drugs could enhance patient compliance and expand treatment options. This research provides a potential strategy for overcoming challenges in peptide drug delivery.","specificNumbers":"","methodology":"The study involved testing various formulations in rat and pig models to assess peptide stability and absorption.","limitations":"The study was conducted in animal models, and results may not directly translate to humans. Further research is needed to confirm findings in clinical settings."},{"rthcId":"RPEP-06549","title":"Cancer and cardiovascular disease: can understanding the mechanisms of cardiovascular injury guide us to optimise care in cancer survivors?","authors":"Truong, Lan-Linh; Scott, Laura; Pal, Raveen S; Jalink, Mathew; Gunasekara, Sanjeeva; Wijeratne, Don Thiwanka","year":2022,"journal":"Ecancermedicalscience, 16, 1430","doi":"10.3332/ecancer.2022.1430","pmid":"36158986","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Beta blockers and ACE-inhibitors improved left ventricular ejection fraction in cancer survivors with LVEF decline.","whyItMatters":"Improving cardiovascular care for cancer survivors can significantly enhance their overall health and quality of life. This is particularly crucial in low and middle-income countries where resources are limited.","specificNumbers":"","methodology":"The study reviews existing literature on the relationship between cancer therapies and cardiovascular health, focusing on pharmacotherapy outcomes.","limitations":"The study primarily reviews existing literature, lacking new clinical trials specifically involving cancer survivors. Many relevant studies exclude this population."},{"rthcId":"RPEP-06550","title":"Rational Strategy for Designing Peptidomimetic Small Molecules Based on Cyclic Peptides Targeting Protein-Protein Interaction between CTLA-4 and B7-1.","authors":"Tsuihiji, Kumiko; Honda, Eiji; Kojoh, Kanehisa; Katoh, Shizue; Taguri, Tomonori; Yoshimori, Atsushi; Takashima, Hajime","year":2022,"journal":"Pharmaceuticals (Basel, Switzerland), 15(12)","doi":"10.3390/ph15121506","pmid":"36558957","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Generated small-molecule compounds with IC50 values in the single-digit μM range against CTLA-4.","whyItMatters":"Targeting protein-protein interactions is crucial for developing effective therapies. This new strategy could streamline the design of small-molecule drugs, making them more accessible.","specificNumbers":"","methodology":"The study utilized ribosomal display to identify inhibitory cyclic peptides, followed by conversion to small molecules using PepMetics® scaffolds.","limitations":"The study primarily focuses on in vitro results, which may not directly translate to in vivo efficacy in humans."},{"rthcId":"RPEP-06551","title":"Antimicrobial peptide expression in the cockroach gut during enterobacterial infection is specific and influenced by type III secretion.","authors":"Turner, Matthew; Pietri, Jose E","year":2022,"journal":"Biology open, 11(5)","doi":"10.1242/bio.059414","pmid":"35611712","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Cockroaches induced antimicrobial peptide expression after ingesting live Salmonella but not E. coli or heat-killed Salmonella.","whyItMatters":"Understanding how cockroaches manage bacterial infections can provide insights into insect immunity and help in controlling disease transmission by these pests.","specificNumbers":"","methodology":"The study used qRT-PCR to analyze the expression of five antimicrobial peptide genes in cockroach guts after bacterial ingestion.","limitations":"The study focused only on specific bacteria and may not represent all interactions in the cockroach gut."},{"rthcId":"RPEP-06552","title":"Characterization of the physicochemical interactions between exenatide and two intestinal permeation enhancers: Sodium caprate (C10) and salcaprozate sodium (SNAC).","authors":"Twarog, Caroline; Fattal, Elias; Noiray, Magali; Illel, Brigitte; Brayden, David J; Taverna, Myriam; Hillaireau, Hervé","year":2022,"journal":"International journal of pharmaceutics, 626, 122131","doi":"10.1016/j.ijpharm.2022.122131","pmid":"36028084","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Exenatide showed weak interactions with sodium caprate and SNAC, with dissociation constants of approximately 10 µM and 30 µM, respectively.","whyItMatters":"Understanding these interactions is crucial for improving the oral bioavailability of peptide drugs like exenatide. This knowledge could lead to better formulations for effective oral delivery.","specificNumbers":"","methodology":"The study employed dynamic light scattering, surface plasmon resonance, isothermal titration calorimetry, and affinity capillary electrophoresis to analyze the interactions.","limitations":"The study primarily focuses on in vitro interactions, which may not fully represent in vivo conditions in the human gastrointestinal tract."},{"rthcId":"RPEP-06553","title":"Injectable Biodegradable Silica Depot: Two Months of Sustained Release of the Blood Glucose Lowering Peptide, Pramlintide.","authors":"Tyagi, Puneet; Koskinen, Mika; Mikkola, Jari; Sarkhel, Sanjay; Leino, Lasse; Seth, Asha; Madalli, Shimona; Will, Sarah; Howard, Victor G; Brant, Helen; Corkill, Dominic","year":2022,"journal":"Pharmaceutics, 14(3)","doi":"10.3390/pharmaceutics14030553","pmid":"35335929","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Pramlintide released from the silica depot maintained a steady serum concentration of 500 pM for 60 days.","whyItMatters":"This method could improve diabetes treatment by reducing the need for frequent dosing and minimizing hypoglycemia risks. It represents a significant advancement in drug delivery technology.","specificNumbers":"","methodology":"The study involved formulating a silica microparticle hydrogel depot and testing its drug release in a rat model.","limitations":"The study was conducted in rats, and results may not directly translate to humans. Further studies are needed to assess safety and efficacy in human subjects."},{"rthcId":"RPEP-06554","title":"Opioidergic pathways and kisspeptin in the regulation of female reproduction in mammals.","authors":"Uenoyama, Yoshihisa; Tsuchida, Hitomi; Nagae, Mayuko; Inoue, Naoko; Tsukamura, Hiroko","year":2022,"journal":"Frontiers in neuroscience, 16, 958377","doi":"10.3389/fnins.2022.958377","pmid":"36033602","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Endogenous opioid peptides modulate GnRH release in response to various cues.","whyItMatters":"Understanding these pathways can help in addressing reproductive health issues in females. It also provides insights into how stress and nutrition can impact fertility.","specificNumbers":"","methodology":"The study includes a review of existing literature and discusses the mechanisms of opioid peptides in hormone regulation.","limitations":"The study primarily reviews existing literature, which may not encompass all recent findings."},{"rthcId":"RPEP-06555","title":"Maintenance of glycaemic control with liraglutide versus oral antidiabetic drugs as add-on therapies in patients with type 2 diabetes uncontrolled with metformin alone: A randomized clinical trial in primary care (LIRA-PRIME).","authors":"Unger, Jeff; Allison, Dale C; Kaltoft, Margit; Lakkole, Kavitha; Panda, Jayant K; Ramesh, Chethana; Sargin, Mehmet; Smolyarchuk, Elena; Twine, Melissa; Wolthers, Benjamin; Yarimbas, Gizem; Zoghbi, Marouan","year":2022,"journal":"Diabetes, obesity & metabolism, 24(2), 204-211","doi":"10.1111/dom.14566","pmid":"34622567","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06556","title":"LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trial.","authors":"Urva, Shweta; Coskun, Tamer; Loh, Mei Teng; Du, Yu; Thomas, Melissa K; Gurbuz, Sirel; Haupt, Axel; Benson, Charles T; Hernandez-Illas, Martha; D'Alessio, David A; Milicevic, Zvonko","year":2022,"journal":"Lancet (London, England), 400(10366), 1869-1881","doi":"10.1016/S0140-6736(22)02033-5","pmid":"36354040","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"At 12 weeks, the three highest dose groups of LY3437943 showed significant placebo-adjusted reductions in mean daily plasma glucose: -2.8, -3.1, and -2.9 mmol/L respectively. HbA1c decreased by -1.4%, -1.6%, and -1.2% (placebo-adjusted) at these doses. Bodyweight reduction was dose-dependent, reaching -8.96 kg (90% CI -11.16 to -6.75) in the highest dose group (3/6/9/12 mg escalation).\n\nThe peptide's pharmacokinetics were dose-proportional with a half-life of approximately 6 days, supporting once-weekly dosing. Treatment-emergent adverse events occurred in 63% of LY3437943 recipients (vs 54% placebo), primarily gastrointestinal. However, 29 of 72 participants discontinued prematurely across all groups.","whyItMatters":"This trial represents the next frontier in peptide-based metabolic medicine. While GLP-1 agonists (semaglutide) and dual GIP/GLP-1 agonists (tirzepatide) have transformed diabetes and obesity treatment, adding glucagon receptor activity could deliver even greater weight loss by increasing energy expenditure. This 'triple agonist' approach is the most ambitious attempt yet to harness multiple gut hormone pathways in a single peptide molecule.","specificNumbers":"","methodology":"Phase 1b, proof-of-concept, double-blind, placebo-controlled, randomized, multiple-ascending dose trial at four US sites. Adults aged 20–70 with type 2 diabetes (HbA1c 7.0–10.5%, BMI 23–50) received once-weekly subcutaneous LY3437943, placebo, or dulaglutide 1.5 mg for 12 weeks. Five ascending dose cohorts were studied, with the two highest using stepwise dose escalation. Each cohort randomized minimum 9 to LY3437943, 3 to placebo, and 1 to dulaglutide. Primary outcome was safety/tolerability; pharmacodynamics and pharmacokinetics were secondary.","limitations":"This is a small phase 1b study (72 participants) designed primarily for safety rather than efficacy. The 12-week duration is short for assessing long-term metabolic outcomes. The high discontinuation rate (29/72 = 40%) across all groups raises concerns about tolerability and study retention. The dulaglutide comparator arm (only 5 participants) was too small for meaningful efficacy comparison. Gastrointestinal side effects were common, consistent with the GLP-1 class. The study was funded by Eli Lilly, the drug's developer."},{"rthcId":"RPEP-06557","title":"Nanomedicine based potentially transformative strategies for colon targeting of peptides: State-of-the-art.","authors":"Vambhurkar, Ganesh; Amulya, Etikala; Sikder, Anupama; Shah, Saurabh; Famta, Paras; Khatri, Dharmendra Kumar; Singh, Shashi Bala; Srivastava, Saurabh","year":2022,"journal":"Colloids and surfaces. B, Biointerfaces, 219, 112816","doi":"10.1016/j.colsurfb.2022.112816","pmid":"36108367","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review establishes that the colon offers significant advantages for oral peptide delivery compared to upper GI segments: lower proteolytic enzyme activity, enhanced retention time, and conditions more favorable for peptide absorption. Nanomedicine strategies — including nanoparticles, liposomes, and other carrier systems — can protect peptides through the harsh upper GI environment and enable colon-specific release.\n\nThe authors classify therapeutic peptides and map them to appropriate nanomedicine delivery strategies, while also addressing the regulatory hurdles that currently slow clinical translation of these systems.","whyItMatters":"Most therapeutic peptides must be injected, which limits patient compliance and quality of life. Cracking the oral delivery problem — especially for colon-targeted peptides — could transform treatment for conditions like inflammatory bowel disease, colorectal cancer, and metabolic disorders. Nanomedicine is one of the most promising approaches to making this feasible.","specificNumbers":"","methodology":"This is a state-of-the-art review that surveys the published literature on nanomedicine approaches for oral delivery of peptides to the colon. The authors compile and categorize peptide classification systems, nanomedicine delivery strategies, and regulatory considerations for clinical translation.","limitations":"This is a review article and presents no new experimental data. The abstract does not quantify the comparative performance of different nanomedicine strategies or provide specific bioavailability numbers. Many of the described approaches remain preclinical, and the gap between laboratory results and clinical translation for oral peptide delivery systems remains substantial."},{"rthcId":"RPEP-06558","title":"Effects of Dapagliflozin and Combination Therapy With Exenatide on Food-Cue Induced Brain Activation in Patients With Type 2 Diabetes.","authors":"van Ruiten, Charlotte C; Veltman, Dick J; Schrantee, Anouk; van Bloemendaal, Liselotte; Barkhof, Frederik; Kramer, Mark H H; Nieuwdorp, Max; IJzerman, Richard G","year":2022,"journal":"The Journal of clinical endocrinology and metabolism, 107(6), e2590-e2599","doi":"10.1210/clinem/dgac043","pmid":"35134184","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"After 10 days, dapagliflozin increased CNS activation, while exenatide decreased it; after 16 weeks, combination therapy reduced activation in the right amygdala.","whyItMatters":"Understanding how these medications affect brain responses can help improve weight management strategies for people with type 2 diabetes. It sheds light on the mechanisms behind weight loss discrepancies observed with these treatments.","specificNumbers":"","methodology":"The study was a 16-week, double-blind, randomized, placebo-controlled trial involving 64 obese participants with type 2 diabetes.","limitations":"The study's sample size was relatively small, and results may not be generalizable to all populations with type 2 diabetes."},{"rthcId":"RPEP-06559","title":"Health care resource utilization and costs associated with treatment among patients initiating calcitonin gene-related peptide inhibitors vs other preventive migraine treatments in the United States.","authors":"Varnado, Oralee J; Manjelievskaia, Janna; Ye, Wenyu; Perry, Allison; Schuh, Kory; Wenzel, Richard","year":2022,"journal":"Journal of managed care & specialty pharmacy, 28(8), 818-829","doi":"10.18553/jmcp.2022.28.8.818","pmid":"35876297","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CGRP mAbs led to a 1.5% decrease in acute medication fills and a $374 reduction in preventive medication costs compared to standard treatments.","whyItMatters":"Understanding the cost implications of new migraine treatments can help inform patient choices and healthcare policies. This study suggests that CGRP mAbs may offer long-term savings despite higher upfront costs.","specificNumbers":"","methodology":"The study was a retrospective observational analysis using insurance claims data, comparing patients who initiated CGRP mAbs with those on standard preventive treatments.","limitations":"The study relied on insurance claims data, which may not capture all healthcare costs, and it focused only on direct costs without assessing indirect costs."},{"rthcId":"RPEP-06560","title":"Patient characteristics and treatment utilization among patients with migraine initiating self-injectable calcitonin gene-related peptide monoclonal antibody and novel acute medication.","authors":"Varnado, Oralee J; Hoyt, Maggie; Ye, Wenyu; Nicholson, Robert","year":2022,"journal":"Current medical research and opinion, 38(8), 1451-1457","doi":"10.1080/03007995.2022.2091333","pmid":"35762152","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 3,497 migraine patients initiating self-injectable CGRP monoclonal antibodies alongside novel acute medications, the majority had chronic migraine (64.4–71.4%) and were already on both preventive and acute treatments. Most patients received combination therapy with both preventive and acute medications targeting the CGRP pathway — either both binding CGRP receptors (43.6–59.0%) or preventive medication binding CGRP ligands paired with acute medication binding CGRP receptors (34.9–51.9%).\n\nPatients used both medications concurrently for an average of about 30 days, and prescribing patterns were consistent across different healthcare provider types.","whyItMatters":"CGRP-targeting peptide therapies represent a major breakthrough in migraine treatment. This study provides the first real-world look at how doctors are actually combining these new preventive and acute CGRP medications, revealing that dual CGRP-pathway targeting is the dominant prescribing pattern — information that can guide treatment decisions and insurance coverage policies.","specificNumbers":"n=3,497 total · 64.4–71.4% chronic migraine · 88.8% female · Mean age 44.7–51.2 years · ~30 days concomitant use · 43.6–59.0% dual CGRP receptor targeting","methodology":"Retrospective observational study using insurance claims data from IBM MarketScan Research Database and Optum's Clinformatics Data Mart (May 2017–December 2020). Included adult patients initiating self-injectable CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab) alongside novel acute medications (lasmiditan, rimegepant, ubrogepant) with at least 3 months of overlapping use.","limitations":"As a claims-based observational study, it cannot measure treatment effectiveness, patient-reported outcomes, or reasons for prescribing decisions. Claims data may not capture medication samples, over-the-counter use, or non-adherence. The study describes patterns but cannot establish whether dual CGRP-pathway targeting produces better outcomes than other combinations."},{"rthcId":"RPEP-06561","title":"Treatment Patterns for Calcitonin Gene-Related Peptide Monoclonal Antibodies Including Galcanezumab versus Conventional Preventive Treatments for Migraine: A Retrospective US Claims Study.","authors":"Varnado, Oralee J; Manjelievskaia, Janna; Ye, Wenyu; Perry, Allison; Schuh, Kory; Wenzel, Richard","year":2022,"journal":"Patient preference and adherence, 16, 821-839","doi":"10.2147/PPA.S346660","pmid":"35378732","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Patients on CGRP mAb had higher persistence (212.5 vs 131.9 days) and adherence (PDC: 55.1% vs 35.2%) compared to SOC.","whyItMatters":"Understanding treatment adherence can help improve migraine management strategies and patient outcomes. This study highlights the potential benefits of newer migraine treatments.","specificNumbers":"","methodology":"The study used a retrospective analysis of claims data, comparing treatment patterns in matched patient groups over 12 months.","limitations":"The study is retrospective and relies on claims data, which may not capture all relevant clinical details or patient experiences."},{"rthcId":"RPEP-06562","title":"Phase I/II clinical trial of a helper peptide vaccine plus PD-1 blockade in PD-1 antibody-naïve and PD-1 antibody-experienced patients with melanoma (MEL64).","authors":"Vavolizza, Rick Daniel; Petroni, Gina R; Mauldin, Ileana S; Chianese-Bullock, Kimberly A; Olson, Walter C; Smith, Kelly T; Dengel, Lynn T; Haden, Kathleen; Grosh, William W; Kaur, Varinder; Varhegyi, Nikole; Gaughan, Elizabeth M; Slingluff, Craig L","year":2022,"journal":"Journal for immunotherapy of cancer, 10(9)","doi":"10.1136/jitc-2022-005424","pmid":"36100309","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06563","title":"Protection against stroke with glucagon-like peptide-1 receptor agonists: a comprehensive review of potential mechanisms.","authors":"Vergès, Bruno; Aboyans, Victor; Angoulvant, Denis; Boutouyrie, Pierre; Cariou, Bertrand; Hyafil, Fabien; Mohammedi, Kamel; Amarenco, Pierre","year":2022,"journal":"Cardiovascular diabetology, 21(1), 242","doi":"10.1186/s12933-022-01686-3","pmid":"36380358","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1RAs improve stroke outcomes by enhancing plaque stability and lowering risk factors.","whyItMatters":"Understanding how GLP-1RAs protect against strokes could lead to better treatments for diabetic patients at risk of stroke.","specificNumbers":"","methodology":"This study is a comprehensive review of randomized controlled trials and animal studies.","limitations":"The review primarily focuses on animal studies, which may not fully translate to human outcomes."},{"rthcId":"RPEP-06564","title":"Cardiovascular efficacy of liraglutide and semaglutide in individuals with diabetes and peripheral artery disease.","authors":"Verma, Subodh; Al-Omran, Mohammed; Leiter, Lawrence A; Mazer, C David; Rasmussen, Søren; Saevereid, Hans A; Sejersten Ripa, Maria; Bonaca, Marc P","year":2022,"journal":"Diabetes, obesity & metabolism, 24(7), 1288-1299","doi":"10.1111/dom.14700","pmid":"35332654","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Patients with PAD had a ~35% increased risk of major cardiovascular events, but both liraglutide and semaglutide showed beneficial effects.","whyItMatters":"Understanding the cardiovascular benefits of these medications can help improve treatment strategies for diabetic patients at high risk of heart disease.","specificNumbers":"","methodology":"The study analyzed data from the LEADER and SUSTAIN 6 trials, comparing liraglutide and semaglutide to placebo in patients with type 2 diabetes and high cardiovascular risk.","limitations":"The study's findings are based on trial data, which may not fully represent real-world scenarios."},{"rthcId":"RPEP-06565","title":"The use of erenumab for migraine prophylaxis during pregnancy: A case report and narrative review.","authors":"Vig, Sierra J; Garza, Julia; Tao, Yunting","year":2022,"journal":"Headache, 62(10), 1256-1263","doi":"10.1111/head.14305","pmid":"35467013","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"One case report showed no adverse effects on the baby from erenumab use during pregnancy.","whyItMatters":"Understanding the safety of migraine treatments during pregnancy is crucial for women who suffer from migraines and may become pregnant. This case provides some initial reassurance about the use of erenumab.","specificNumbers":"","methodology":"The study involved a case report and a literature review of safety data on CGRP agents during pregnancy.","limitations":"The study is based on a single case report and limited safety data, which may not be generalizable."},{"rthcId":"RPEP-06566","title":"Cerebrolysin induces hair repigmentation associated to MART-1/Melan-A reactivation.","authors":"Villarreal-Reyna, Gustavo; Garza-Morales, Rodolfo; Soto-Domínguez, Adolfo; Montañez-Guerrero, Lorena; Saucedo-Cárdenas, Odila; Gómez-Flores, Minerva; Ocampo-Garza, Jorge Alejandro; Pérez-Trujillo, José Juan; Montes-de-Oca-Luna, Roberto","year":2022,"journal":"European journal of medical research, 27(1), 257","doi":"10.1186/s40001-022-00889-4","pmid":"36411485","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06567","title":"In vitro digestion of milk proteins including intestinal brush border membrane peptidases. Transepithelial transport of resistant casein domains.","authors":"Vivanco-Maroto, Santiaga María; Santos-Hernández, Marta; Sanchón, Javier; Picariello, Gianluca; Recio, Isidra; Miralles, Beatriz","year":2022,"journal":"Food research international (Ottawa, Ont.), 157, 111238","doi":"10.1016/j.foodres.2022.111238","pmid":"35761550","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Adding brush border membrane (BBM) enzymes to the standard INFOGEST digestion protocol revealed additional peptide cleavage sites beyond pancreatic digestion alone. BBM enzymes (amino- and carboxy-peptidases) reduced total peptide numbers but increased free amino acid concentrations, better approximating real digestion.\n\nComparing the in vitro peptidome with peptides from actual human jejunal aspirates, BBM addition allowed identification of peptides found in vivo — though neither model reproduced the full peptide diversity seen in human digestion. For six beta-casein peptides including beta-casomorphin-7, transepithelial transport through Caco-2 cells showed that N- and C-terminal residue identity was a key determinant of absorption rate.","whyItMatters":"Understanding which bioactive peptides survive digestion and get absorbed is critical for developing functional foods and nutraceuticals. This study improves the standard lab simulation of digestion, making it more predictive of what actually happens in the human gut. The finding that peptide end structure determines absorption rate provides practical guidance for designing peptides with better bioavailability.","specificNumbers":"","methodology":"Casein and whey proteins were digested using the standardized INFOGEST protocol with and without brush border membrane enzymes. Resulting peptides were analyzed by tandem mass spectrometry. The in vitro peptidome was compared with peptides previously identified in human jejunal aspirates after milk protein ingestion. Transepithelial transport of six beta-casein peptides was evaluated using Caco-2 cell monolayers (a standard model of intestinal absorption).","limitations":"The in vitro digestion model, even with BBM enzymes, could not reproduce the full diversity of peptides found in human intestinal fluid, suggesting additional factors are involved in vivo. Caco-2 cells are a simplified model of intestinal absorption that may not fully capture in vivo transport complexity. Only six beta-casein peptides were tested for transport. The study did not assess biological activity of the absorbed peptides."},{"rthcId":"RPEP-06568","title":"AgRP/NPY and POMC neurons in the arcuate nucleus and their potential role in treatment of obesity.","authors":"Vohra, Muhammad Sufyan; Benchoula, Khaled; Serpell, Christopher J; Hwa, Wong Eng","year":2022,"journal":"European journal of pharmacology, 915, 174611","doi":"10.1016/j.ejphar.2021.174611","pmid":"34798121","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06569","title":"Once-Weekly Subcutaneous Semaglutide Improves Fatty Liver Disease in Patients with Type 2 Diabetes: A 52-Week Prospective Real-Life Study.","authors":"Volpe, Sara; Lisco, Giuseppe; Fanelli, Margherita; Racaniello, Davide; Colaianni, Valentina; Triggiani, Domenico; Donghia, Rossella; Crudele, Lucilla; Rinaldi, Roberta; Sabbà, Carlo; Triggiani, Vincenzo; De Pergola, Giovanni; Piazzolla, Giuseppina","year":2022,"journal":"Nutrients, 14(21)","doi":"10.3390/nu14214673","pmid":"36364937","tags":[],"studyType":"prospective-cohort","evidenceStrength":"moderate","keyFinding":"After 52 weeks of once-weekly subcutaneous semaglutide added to metformin, 70% of type 2 diabetes patients with fatty liver disease showed improvement — reducing their liver steatosis by at least one ultrasound-assessed grade. The treatment produced significant decreases in body weight, insulin resistance, liver enzymes, and laboratory markers of hepatic fat accumulation.\n\nNotably, semaglutide preferentially reduced fat mass and visceral adipose tissue (the dangerous belly fat surrounding organs) more than skeletal muscle or lean mass. Ultrasound-measured visceral fat thickness and a 12-point steatosis severity score both declined progressively from 3 months through the full 12-month treatment period.","whyItMatters":"Nonalcoholic fatty liver disease affects roughly 70% of type 2 diabetes patients and can progress to cirrhosis and liver cancer. Until recently, there were no approved drugs specifically for NAFLD — weight loss was the only reliable treatment. This real-world study shows that semaglutide addresses both diabetes and fatty liver simultaneously, with measurable liver improvements in the majority of patients over one year. It adds to growing evidence that GLP-1 agonists may become a cornerstone treatment for metabolic liver disease.","specificNumbers":"n=48 · 52-week treatment · 70% showed steatosis improvement by ≥1 grade · Significant decreases in VAT, liver enzymes, insulin resistance · Preferential fat loss over muscle loss","methodology":"Forty-eight type 2 diabetes patients with NAFLD received once-weekly subcutaneous semaglutide alongside their existing metformin. They were assessed at baseline, 3 months, 6 months, and 12 months. At each visit, body composition was measured using bio-impedance analysis, and liver fat was evaluated by ultrasound imaging with a semiquantitative 12-point steatosis scoring system. Blood tests tracked glucose control, liver enzymes, insulin resistance markers, and calculated indices of hepatic steatosis.","limitations":"This was a single-center, uncontrolled prospective study with only 48 patients — there was no placebo or comparison group, so improvements can't be definitively attributed to semaglutide alone versus lifestyle changes or natural progression. The use of ultrasound rather than MRI for liver fat assessment is less precise. As a real-world study, treatment adherence and concurrent lifestyle modifications weren't strictly controlled."},{"rthcId":"RPEP-06570","title":"Pentadecapeptide BPC 157 and the central nervous system.","authors":"Vukojevic, Jakša; Milavić, Marija; Perović, Darko; Ilić, Spomenko; Čilić, Andrea Zemba; Đuran, Nataša; Štrbe, Sanja; Zoričić, Zoran; Filipčić, Igor; Brečić, Petrana; Seiverth, Sven; Sikirić, Predrag","year":2022,"journal":"Neural regeneration research, 17(3), 482-487","doi":"10.4103/1673-5374.320969","pmid":"34380875","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BPC 157 improved outcomes in stroke, schizophrenia symptoms, and spinal cord injuries in rats.","whyItMatters":"Understanding BPC 157's effects could lead to new treatments for serious brain and nerve conditions. Its potential to address multiple disorders makes it a significant focus for future research.","specificNumbers":"","methodology":"The study involved reviewing recent experiments on BPC 157's effects in rat models of various central nervous system disorders.","limitations":"The study is based on animal models, and results may not directly translate to humans. Further research is needed to confirm efficacy and safety in human subjects."},{"rthcId":"RPEP-06571","title":"Improving Fmoc Solid Phase Synthesis of Human Beta Defensin 3.","authors":"Walewska, Aleksandra; Kosikowska-Adamus, Paulina; Tomczykowska, Marta; Jaroszewski, Bartosz; Prahl, Adam; Bulaj, Grzegorz","year":2022,"journal":"International journal of molecular sciences, 23(20)","doi":"10.3390/ijms232012562","pmid":"36293413","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The optimized synthesis methods increased the yield of HBD-3 significantly, improving efficiency.","whyItMatters":"Enhancing the synthesis of HBD-3 allows for better research into its biological functions and potential medical applications.","specificNumbers":"","methodology":"The study employed Fmoc solid-phase synthesis with optimized resin and coupling reagents, and introduced a diselenide bond for improved folding.","limitations":"The study primarily focuses on synthesis methods and does not address biological testing of the synthesized peptide."},{"rthcId":"RPEP-06572","title":"Thymosin β4 Protects against Cardiac Damage and Subsequent Cardiac Fibrosis in Mice with Myocardial Infarction.","authors":"Wang, Fei; He, Yajuan; Yao, Naijuan; Ruan, Litao; Tian, Zhen","year":2022,"journal":"Cardiovascular therapeutics, 2022, 1308651","doi":"10.1155/2022/1308651","pmid":"35712678","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Adeno-associated virus delivery of thymosin β4 (AAV-Tβ4) in mice with surgically induced heart attacks significantly reduced oxidative damage, inflammation, cardiac dysfunction, and fibrosis compared to controls.\n\nAt the cellular level, thymosin β4 counteracted hydrogen peroxide-induced damage in heart muscle cells by restoring mitophagy (the cleanup of damaged mitochondria) and reducing inflammasome activation. It also inhibited the growth of cardiac myofibroblasts — the cells responsible for producing scar tissue — and blocked TGF-β1-induced activation, a key driver of fibrosis. Thymosin β4 was naturally elevated in heart attack tissue, suggesting the body attempts to use this peptide as a protective response.","whyItMatters":"Heart attacks are a leading cause of death worldwide, and the scarring that follows often leads to heart failure. Current treatments focus on restoring blood flow but do little to prevent the fibrosis that weakens the heart over time. Thymosin β4's ability to simultaneously fight inflammation, reduce oxidative damage, and block scar formation addresses multiple aspects of post-heart attack damage — making it an attractive candidate for future cardiac therapies.","specificNumbers":"","methodology":"Researchers first measured thymosin β4 levels in heart tissue from mice with acute heart attacks using qRT-PCR, immunohistochemistry, and Western blot. They then delivered exogenous thymosin β4 via intraperitoneal injection of adeno-associated virus (AAV-Tβ4) to mice with surgically induced heart attacks. Cardiac function was assessed alongside tissue staining (HE and Masson) to evaluate inflammation and fibrosis. In parallel, they tested thymosin β4's effects on isolated mouse cardiac myocytes exposed to hydrogen peroxide stress and on myofibroblasts stimulated with TGF-β1.","limitations":"This was a mouse study, and the cardiovascular system in mice differs from humans in important ways. The study did not report specific group sizes or long-term follow-up beyond the acute and fibrotic phases. The gene therapy delivery method (AAV) may not be the most practical clinical approach. No dose-response data were provided, and the exact signaling pathways require further characterization."},{"rthcId":"RPEP-06573","title":"Semaglutide and Diabetic Retinopathy Risk in Patients with Type 2 Diabetes Mellitus: A Meta-Analysis of Randomized Controlled Trials.","authors":"Wang, Feiyu; Mao, Yinjun; Wang, Hang; Liu, Yiwei; Huang, Pinfang","year":2022,"journal":"Clinical drug investigation, 42(1), 17-28","doi":"10.1007/s40261-021-01110-w","pmid":"34894326","tags":[],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Across 23 randomized controlled trials involving 22,096 patients with type 2 diabetes, semaglutide was not associated with an overall increased risk of diabetic retinopathy compared to all control groups (RR 1.14, 95% CI 0.98–1.33).\n\nHowever, the picture changed in subgroup analyses. Compared specifically to placebo, semaglutide was associated with a 24% increased risk of retinopathy (RR 1.24, 95% CI 1.03–1.50). Two patient groups faced the highest risk: those aged 60 or older (RR 1.27) and those with diabetes duration of 10+ years (RR 1.28). There were 730 total retinopathy cases — 463 in semaglutide groups and 267 in control groups.","whyItMatters":"The SUSTAIN 6 trial raised an alarm when semaglutide-treated patients developed more retinopathy complications than placebo. This meta-analysis pooling 23 trials provides the most comprehensive look at that signal. While the overall risk wasn't statistically significant, the finding that older patients and those with longer diabetes duration face elevated eye risk is clinically important — these are exactly the patients most likely to be prescribed semaglutide. It means eye monitoring should be part of semaglutide treatment planning for high-risk groups.","specificNumbers":"23 RCTs · n=22,096 · 730 DR cases · overall RR 1.14 (95% CI 0.98–1.33) · vs placebo RR 1.24 (95% CI 1.03–1.50) · age ≥60 RR 1.27 · diabetes ≥10 years RR 1.28","methodology":"Systematic review and meta-analysis of randomized controlled trials. Researchers searched electronic databases through April 2021, identified 23 RCTs reporting diabetic retinopathy events in semaglutide vs. control groups, and calculated pooled risk ratios with 95% confidence intervals using Review Manager 5.4. Subgroup analyses examined risk by comparator type, patient age, and diabetes duration.","limitations":"The overall analysis combined trials with different comparators (placebo, active drugs), which may dilute the signal. Individual trial definitions of retinopathy events may have varied. The meta-analysis relied on published trial data and could not access individual patient-level data. The mechanism behind the retinopathy signal (possibly rapid blood sugar improvement) could not be directly assessed."},{"rthcId":"RPEP-06574","title":"Wound healing mechanism of antimicrobial peptide cathelicidin-DM.","authors":"Wang, Guixi; Chen, Zhizhi; Tian, Pan; Han, Qinqin; Zhang, Jinyang; Zhang, A-Mei; Song, Yuzhu","year":2022,"journal":"Frontiers in bioengineering and biotechnology, 10, 977159","doi":"10.3389/fbioe.2022.977159","pmid":"36425652","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Cathelicidin-DM accelerated skin wound healing in mice and promoted cell proliferation and migration.","whyItMatters":"With rising antibiotic resistance, finding new treatments for chronic wounds is crucial. Cathelicidin-DM could offer a novel approach to enhance healing.","specificNumbers":"","methodology":"The study involved in vitro tests on skin cells and a mouse model to assess the effects of cathelicidin-DM on wound healing.","limitations":"The study was conducted in mice, and results may not directly translate to humans. Further clinical studies are needed."},{"rthcId":"RPEP-06575","title":"TRAF6-overexpressing dendritic cells loaded with MUC1 peptide enhance anti-tumor activity in B16-MUC1 melanoma-bearing mice.","authors":"Wang, Jingjing; Liu, Yu; Ni, Weihua; Wu, Xinjie; Zhou, Jianhong; Zhang, Zenan; Zhou, Hongyue; Zhang, Nannan; Jiang, Mengyu; Sang, Qianyu; Yuan, Hongyan; Tai, Guixiang","year":2022,"journal":"International immunopharmacology, 107, 108667","doi":"10.1016/j.intimp.2022.108667","pmid":"35255300","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"TRAF6-overexpressing dendritic cells showed increased expression of costimulatory molecules, MHC molecules, and IL-12 — all markers of enhanced immune cell maturation and Th1-promoting capacity. When pulsed with MUC1 peptide antigen and administered therapeutically to mice bearing B16-MUC1 melanoma tumors, they significantly inhibited tumor growth compared to control dendritic cells.\n\nThe anti-tumor effect was accompanied by increased MUC1-specific Th1 (helper) and Tc1 (cytotoxic/killer) T cell responses, and a decrease in regulatory T cells (Tregs) — a key population that tumors exploit to suppress immunity. This dual effect of boosting anti-tumor immunity while reducing immune suppression makes TRAF6-overexpressing DCs a particularly promising immunotherapy approach.","whyItMatters":"Dendritic cell vaccines are one of the most promising approaches in cancer immunotherapy, but their effectiveness has been limited by poor immune activation. By engineering DCs to overexpress TRAF6 — a key signaling hub for immune activation — researchers significantly enhanced the vaccine's ability to generate anti-tumor immunity. The reduction in Tregs is particularly important because these suppressive cells are a major reason why many cancer immunotherapies fail.","specificNumbers":"","methodology":"Researchers created dendritic cells overexpressing TRAF6 through gene transfer and characterized their maturation markers (costimulatory molecules, MHC, IL-12) in vitro. These DCs were pulsed with MUC1 peptide antigen and then administered to C57BL/6 mice bearing B16-MUC1 melanoma tumors (B16 melanoma cells engineered to express human MUC1). Tumor growth was monitored, and immune responses were assessed by measuring MUC1-specific Th1 and Tc1 responses and Treg levels.","limitations":"This was a mouse study using a transplanted tumor model (B16-MUC1), which does not fully capture the complexity of naturally occurring human melanoma. MUC1 was artificially expressed on mouse melanoma cells to create the model. Gene transfer to overexpress TRAF6 in dendritic cells adds manufacturing complexity for potential clinical translation. Long-term safety of TRAF6-overexpressing DCs was not assessed. The study used a single tumor model and a single antigen peptide."},{"rthcId":"RPEP-06576","title":"Soft-Shelled Turtle Peptides Extend Lifespan and Healthspan in Drosophila.","authors":"Wang, Qianqian; Zhang, Junhui; Zhuang, Jiachen; Shen, Fei; Zhao, Minjie; Du, Juan; Yu, Peng; Zhong, Hao; Feng, Fengqin","year":2022,"journal":"Nutrients, 14(24)","doi":"10.3390/nu14245205","pmid":"36558363","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Soft-shelled turtle peptide (STP) supplementation in Drosophila melanogaster produced multiple anti-aging effects:\n\n- Lifespan extension: 20.23% increase in mean lifespan for males, 9.04% for females\n- Healthspan improvements: maintained climbing ability, enhanced gut barrier integrity, improved antioxidant capacity, and increased resistance to starvation and heat stress\n- No appetite effect: daily food intake was unchanged, ruling out caloric restriction as the mechanism\n\nMechanistically, STP enhanced autophagy and reduced oxidative stress by downregulating the TOR signaling pathway. Molecular analysis showed 95.18% of identified peptide sequences could potentially inhibit TOR through hydrogen bonds, van der Waals forces, hydrophobic interactions, and electrostatic interactions.","whyItMatters":"The TOR (target of rapamycin) pathway is one of the most validated aging pathways across species — from yeast to mammals. Finding that food-derived peptides can inhibit TOR is significant because it suggests a dietary approach to targeting the same pathway that the longevity drug rapamycin targets, potentially without rapamycin's immunosuppressive side effects. While this is fruit fly research, TOR pathway biology is highly conserved in humans.","specificNumbers":"","methodology":"Drosophila melanogaster (fruit flies) were supplemented with soft-shelled turtle peptides and compared to controls. Lifespan was measured across male and female populations. Healthspan was assessed through climbing assays, gut barrier integrity (Smurf assay), and stress resistance tests (starvation and heat). Oxidative stress markers were measured. TOR pathway signaling and autophagy markers were analyzed to determine the molecular mechanism. Peptide sequences were identified and their potential TOR-binding interactions were modeled computationally.","limitations":"Drosophila (fruit flies) are useful model organisms but are extremely distant from humans. The sex difference in lifespan extension (20% in males vs. 9% in females) is notable and unexplained. The TOR-binding predictions are computational and not validated with direct binding assays. The specific peptide sequences responsible for the effect were not isolated — STP is a mixture. The dose used may not translate to achievable human dietary intake. Long-term safety in any mammalian model was not assessed."},{"rthcId":"RPEP-06577","title":"Therapeutic efficacy of topical blockade of substance P in experimental allergic red eye.","authors":"Wang, Shudan; Liu, Lingjia; Blanco, Tomas; Ge, Hongyan; Xia, Yutong; Pang, Kunpeng; Chen, Yihe; Dana, Reza","year":2022,"journal":"The ocular surface, 26, 184-190","doi":"10.1016/j.jtos.2022.08.008","pmid":"36067981","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Topical histamine induced significant ocular redness (peaking at 10 minutes) along with increased substance P levels in tears. The NK1R antagonist L-703,606 was effective in two scenarios:\n\n1. Prevention: Applied 10 minutes before histamine, it significantly reduced the ocular redness index (ORI) and suppressed the inflammatory response.\n2. Treatment: Applied at peak redness (10 minutes after histamine), it still effectively reduced ORI.\n\nIn both cases, L-703,606 suppressed conjunctival blood vessel dilation, decreased eosinophil and neutrophil infiltration, reduced inflammatory cytokine expression, and lowered substance P levels in tears.","whyItMatters":"Allergic conjunctivitis affects hundreds of millions of people worldwide and current treatments (antihistamines, mast cell stabilizers) don't work for everyone. This study reveals substance P as a key mediator of allergic eye redness and shows that blocking it with topical eye drops can both prevent and treat the condition. This could lead to a new class of eye drops targeting neuropeptide signaling for allergy-related eye conditions.","specificNumbers":"","methodology":"Allergic red eye was induced in guinea pigs using topical histamine application. A specific substance P receptor (NK1R) antagonist, L-703,606, was applied topically either 10 minutes before or 10 minutes after histamine challenge. Eye redness was quantified using the ocular redness index (ORI) from serial images over 60 minutes. Conjunctival tissues were examined histologically for blood vessel changes and immune cell infiltration. Tear fluid SP concentrations and conjunctival inflammatory cytokine levels were also measured.","limitations":"This is an animal study in guinea pigs using an acute histamine-induced model, which may not fully represent the chronic, multifactorial nature of human allergic conjunctivitis. Only one NK1R antagonist (L-703,606) was tested at one concentration. The observation period was limited to 60 minutes after induction. Potential side effects of chronic topical NK1R antagonist use on the eye were not assessed."},{"rthcId":"RPEP-06578","title":"Efficacy and safety of monoclonal antibody against calcitonin gene-related peptide or its receptor for migraine patients with prior preventive treatment failure: a network meta-analysis.","authors":"Wang, Xing; Wen, Dingke; He, Qiang; You, Chao; Ma, Lu","year":2022,"journal":"The journal of headache and pain, 23(1), 105","doi":"10.1186/s10194-022-01472-2","pmid":"36071388","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CGRP mAbs reduced monthly migraine days by an average of 1.55 days compared to receptor mAbs.","whyItMatters":"This research provides insights into effective migraine treatments for patients who have not benefited from earlier therapies, potentially improving their quality of life.","specificNumbers":"","methodology":"The study conducted a network meta-analysis of randomized clinical trials involving adult migraine patients with previous treatment failures.","limitations":"The study is limited to the data available from the included trials, which may not cover all patient demographics or treatment scenarios."},{"rthcId":"RPEP-06579","title":"Apple Polyphenols Extracts Ameliorate High Carbohydrate Diet-Induced Body Weight Gain by Regulating the Gut Microbiota and Appetite.","authors":"Wang, Xinjing; Liu, Fang; Cui, Yuan; Yin, Yan; Li, Shilan; Li, Xinli","year":2022,"journal":"Journal of agricultural and food chemistry, 70(1), 196-210","doi":"10.1021/acs.jafc.1c07258","pmid":"34935369","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Mice given APE showed significant weight reduction and improved glucose tolerance compared to those on a high carbohydrate diet.","whyItMatters":"Understanding how natural compounds like apple polyphenols can regulate appetite and gut health may lead to new strategies for managing obesity and related metabolic disorders.","specificNumbers":"","methodology":"The study involved 100 male mice divided into seven groups, fed different diets for 12 weeks, including high carbohydrate diets with varying doses of APE.","limitations":"The study was conducted in mice, which may not fully represent human responses, and long-term effects were not assessed."},{"rthcId":"RPEP-06580","title":"A Hydrogel as a Bespoke Delivery Platform for Stromal Cell-Derived Factor-1.","authors":"Wang, Yi; Penna, Vanessa; Williams, Richard J; Parish, Clare L; Nisbet, David R","year":2022,"journal":"Gels (Basel, Switzerland), 8(4)","doi":"10.3390/gels8040224","pmid":"35448125","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The hydrogel supports increased neuronal differentiation and larger graft cores without hindering growth.","whyItMatters":"This hydrogel could significantly enhance therapies for brain injuries by improving cell integration and function. It represents a promising step toward more effective regenerative treatments.","specificNumbers":"","methodology":"The researchers engineered a hydrogel that incorporates SDF-1 and tested its effects on neural progenitor cells.","limitations":"The study primarily focuses on in vitro results, which may not fully translate to in vivo applications in humans."},{"rthcId":"RPEP-06581","title":"Signaling profiles in HEK 293T cells co-expressing GLP-1 and GIP receptors.","authors":"Wang, Yu-Zhe; Yang, De-Hua; Wang, Ming-Wei","year":2022,"journal":"Acta pharmacologica Sinica, 43(6), 1453-1460","doi":"10.1038/s41401-021-00758-6","pmid":"34446852","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GIP induced cAMP accumulation while GLP-1 biased towards β-arrestin 2 recruitment.","whyItMatters":"Understanding how these receptors interact can improve diabetes treatments. It may lead to better-designed drugs that target these pathways more effectively.","specificNumbers":"","methodology":"The study involved co-expressing GLP-1 and GIP receptors in HEK 293T cells to analyze their signaling profiles.","limitations":"The study was conducted in a cell model, which may not fully replicate human physiology."},{"rthcId":"RPEP-06582","title":"Sulfonium-Tethered Peptide.","authors":"Wang, Yuena; Yin, Feng; Li, Zigang","year":2022,"journal":"Methods in molecular biology (Clifton, N.J.), 2530, 169-175","doi":"10.1007/978-1-0716-2489-0_12","pmid":"35761049","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The new methods significantly enhance peptide stability and cellular uptake.","whyItMatters":"Improving peptide stability and uptake can lead to more effective drug delivery systems. This research could pave the way for new therapeutic applications.","specificNumbers":"","methodology":"The study developed and tested various peptide synthesis methods, including macrocyclization techniques.","limitations":"The study primarily focuses on synthesis methods without extensive in vivo testing."},{"rthcId":"RPEP-06583","title":"Peptide-Calcium Chelate from Antler (Cervus elaphus) Bone Enhances Calcium Absorption in Intestinal Caco-2 Cells and D-gal-Induced Aging Mouse Model.","authors":"Wang, Zhaoguo; Zhai, Xiaorui; Fang, Jiayuan; Wu, Hongyan; Cheng, Yunyun; Gao, Yuan; Chen, Xi; Zheng, Shuo; Liu, Songcai; Hao, Linlin","year":2022,"journal":"Nutrients, 14(18)","doi":"10.3390/nu14183738","pmid":"36145113","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"From 1 gram of antler bone, 0.14 grams of calcium was extracted. The peptide-calcium chelate rate was 53.68 ± 1.80%, with glycine, proline, and glutamic acid residues in the antler bone peptides (ABPs) contributing most to calcium binding affinity. Infrared spectroscopy confirmed calcium interacted with amino nitrogen atoms and carboxyl oxygen atoms.\n\nIn Caco-2 intestinal cell monolayers, ABPs significantly increased calcium transport. In D-galactose-induced aging mice, the ABPs + antler bone calcium group showed higher serum calcium and PINP (bone formation marker), lower phosphorus, ALP, and CTX-1 (bone resorption markers), and significantly higher tibia index and tibia calcium content — demonstrating both increased bone formation and inhibited bone resorption.","whyItMatters":"Calcium supplements are widely used for osteoporosis prevention, but standard calcium salts are often poorly absorbed. Peptide-calcium chelates represent a more bioavailable form where peptides act as carriers that help calcium cross the intestinal wall. Deer antler bones, a traditional medicine ingredient in East Asia, provide both the peptide carriers and the calcium source in a single natural material — an elegant approach to calcium supplementation that could improve outcomes for age-related bone loss.","specificNumbers":"","methodology":"Antler bone calcium (AB-Ca) and bioactive peptides (ABPs) were extracted from red deer (Cervus elaphus) antler bones. Peptide-calcium chelation was characterized using mass spectrometry, Fourier transform infrared spectroscopy, and scanning electron microscopy. Calcium absorption was tested using a Caco-2 cell monolayer model. In vivo efficacy was assessed in D-galactose-induced aging mice, measuring serum calcium, phosphorus, PINP, ALP, CTX-1, and tibia calcium content and index.","limitations":"The D-galactose aging mouse model does not perfectly replicate human postmenopausal osteoporosis, which is the primary clinical target. Specific peptide sequences responsible for calcium chelation were not fully characterized. The study did not compare antler peptide-calcium chelates to standard calcium supplements (like calcium carbonate or citrate). Exact dosing and treatment duration in the mouse model were not detailed in the abstract. Human clinical validation is needed."},{"rthcId":"RPEP-06584","title":"The novel proteomic signature for cardiac allograft vasculopathy.","authors":"Wei, Dongmei; Trenson, Sander; Van Keer, Jan M; Melgarejo, Jesus; Cutsforth, Ella; Thijs, Lutgarde; He, Tianlin; Latosinska, Agnieszka; Ciarka, Agnieszka; Vanassche, Thomas; Van Aelst, Lucas; Janssens, Stefan; Van Cleemput, Johan; Mischak, Harald; Staessen, Jan A; Verhamme, Peter; Zhang, Zhen-Yu","year":2022,"journal":"ESC heart failure, 9(2), 1216-1227","doi":"10.1002/ehf2.13796","pmid":"35005846","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06585","title":"Corn peptides improved obesity-induced non-alcoholic fatty liver disease through relieving lipid metabolism, insulin resistance and oxidative stress.","authors":"Wei, Kang; Wei, Yang; Xu, Weidong; Lu, Feng; Ma, Haile","year":2022,"journal":"Food & function, 13(10), 5782-5793","doi":"10.1039/d2fo00199c","pmid":"35537139","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CPs reduced liver lipid accumulation and improved glucose tolerance in rats fed a high-fat diet.","whyItMatters":"NAFLD is a growing health concern, and finding effective treatments is crucial. This research suggests that corn peptides could be a promising option.","specificNumbers":"","methodology":"The study used SD rats to model NAFLD and LO2 cells to simulate liver conditions, assessing various health markers.","limitations":"The study was conducted in rats, and results may not directly translate to humans."},{"rthcId":"RPEP-06586","title":"ToxIBTL: prediction of peptide toxicity based on information bottleneck and transfer learning.","authors":"Wei, Lesong; Ye, Xiucai; Sakurai, Tetsuya; Mu, Zengchao; Wei, Leyi","year":2022,"journal":"Bioinformatics (Oxford, England), 38(6), 1514-1524","doi":"10.1093/bioinformatics/btac006","pmid":"34999757","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06587","title":"Thymosin α-1 Reverses M2 Polarization of Tumor-Associated Macrophages during Efferocytosis.","authors":"Wei, Yi-Ting; Wang, Xu-Ru; Yan, Chunguang; Huang, Fang; Zhang, Yunpeng; Liu, Xueming; Wen, Zhi-Fa; Sun, Xiao-Tong; Zhang, Yue; Chen, Yong-Qiang; Gao, Rong; Pan, Ning; Wang, Li-Xin","year":2022,"journal":"Cancer research, 82(10), 1991-2002","doi":"10.1158/0008-5472.CAN-21-4260","pmid":"35364609","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06588","title":"Estimated Life-Years Gained Free of New or Recurrent Major Cardiovascular Events With the Addition of Semaglutide to Standard of Care in People With Type 2 Diabetes and High Cardiovascular Risk.","authors":"Westerink, Jan; Matthiessen, Kasper Sommer; Nuhoho, Solomon; Fainberg, Udi; Lyng Wolden, Michael; Østergaard, Helena Bleken; Visseren, Frank; Sattar, Naveed","year":2022,"journal":"Diabetes care, 45(5), 1211-1218","doi":"10.2337/dc21-1138","pmid":"35263432","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Patients gained an average of 1.7 life-years free of cardiovascular events, with variations based on risk.","whyItMatters":"Understanding the benefits of semaglutide can guide treatment decisions for high-risk diabetes patients, potentially improving their quality of life.","specificNumbers":"","methodology":"The study used pooled data from two clinical trials to estimate life-years free of cardiovascular disease (CVD) with semaglutide.","limitations":"The study is based on post hoc analysis and may not account for all variables affecting cardiovascular risk."},{"rthcId":"RPEP-06589","title":"Gastrointestinal tolerability of once-weekly semaglutide 2.4 mg in adults with overweight or obesity, and the relationship between gastrointestinal adverse events and weight loss.","authors":"Wharton, Sean; Calanna, Salvatore; Davies, Melanie; Dicker, Dror; Goldman, Bryan; Lingvay, Ildiko; Mosenzon, Ofri; Rubino, Domenica M; Thomsen, Mette; Wadden, Thomas A; Pedersen, Sue D","year":2022,"journal":"Diabetes, obesity & metabolism, 24(1), 94-105","doi":"10.1111/dom.14551","pmid":"34514682","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06590","title":"Emerging Roles of Vitamin D-Induced Antimicrobial Peptides in Antiviral Innate Immunity.","authors":"White, John H","year":2022,"journal":"Nutrients, 14(2)","doi":"10.3390/nu14020284","pmid":"35057465","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Vitamin D induces the production of antimicrobial peptides that enhance antiviral immunity.","whyItMatters":"Understanding the role of Vitamin D in immunity could lead to better prevention strategies for infections. This knowledge is especially relevant in the context of ongoing viral threats like COVID-19.","specificNumbers":"","methodology":"The study reviews existing evidence on the role of Vitamin D in immune responses, focusing on antimicrobial peptides.","limitations":"The study is a review and does not present new experimental data; thus, it relies on existing literature."},{"rthcId":"RPEP-06591","title":"Research into the Bioengineering of a Novel α-Conotoxin from the Milked Venom of Conus obscurus.","authors":"Wiere, Sean; Sugai, Christopher; Espiritu, Michael J; Aurelio, Vincent P; Reyes, Chloe D; Yuzon, Nicole; Whittal, Randy M; Tytgat, Jan; Peigneur, Steve; Bingham, Jon-Paul","year":2022,"journal":"International journal of molecular sciences, 23(20)","doi":"10.3390/ijms232012096","pmid":"36292948","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The synthetic α-[P9K] conotoxin OI showed a 2.85 to 18.4 fold increase in potency.","whyItMatters":"This research could lead to the development of new pain relief medications based on conotoxins, which may offer alternatives to current treatments.","specificNumbers":"","methodology":"The study involved isolating and synthesizing conotoxins, creating analogs with mutations and modifications, and testing their effects on specific receptors.","limitations":"The study primarily focuses on in vitro assays, and results may not directly translate to clinical applications in humans."},{"rthcId":"RPEP-06592","title":"Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension.","authors":"Wilding, John P H; Batterham, Rachel L; Davies, Melanie; Van Gaal, Luc F; Kandler, Kristian; Konakli, Katerina; Lingvay, Ildiko; McGowan, Barbara M; Oral, Tugce Kalayci; Rosenstock, Julio; Wadden, Thomas A; Wharton, Sean; Yokote, Koutaro; Kushner, Robert F","year":2022,"journal":"Diabetes, obesity & metabolism, 24(8), 1553-1564","doi":"10.1111/dom.14725","pmid":"35441470","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06593","title":"First Report of Screening of Novel Angiotensin-I Converting Enzyme Inhibitory Peptides Derived from the Red Alga Acrochaetium sp.","authors":"Windarto, Seto; Lee, Meng-Chou; Nursyam, Happy; Hsu, Jue-Liang","year":2022,"journal":"Marine biotechnology (New York, N.Y.), 24(5), 882-894","doi":"10.1007/s10126-022-10152-w","pmid":"36074309","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The peptide VL-9 (sequence VGGSDLQAL), derived from the phycoerythrin protein of Acrochaetium sp. red algae, inhibited ACE with an IC50 value of 433.1 ± 1.08 µM.\n\nMolecular docking confirmed that VL-9 acts as a non-competitive inhibitor, binding ACE outside its catalytic site. This is the first report of any bioactive peptide being identified from this particular red alga species.","whyItMatters":"Synthetic ACE inhibitors are a cornerstone of blood pressure treatment but carry side effects. Finding natural ACE-inhibiting peptides in edible algae could open the door to functional foods or nutraceuticals that help manage hypertension with fewer adverse effects, while also adding commercial value to underutilized marine resources.","specificNumbers":"","methodology":"Proteins from Acrochaetium sp. were digested with several proteolytic enzymes. The resulting hydrolysates were separated using reversed-phase and strong cation exchange chromatography. The most active fraction, generated by α-chymotrypsin digestion, was sequenced and identified as the nine-residue peptide VL-9. ACE inhibitory activity was measured in vitro, and molecular docking simulations were used to model how VL-9 interacts with the enzyme.","limitations":"All experiments were conducted in vitro, so it is unknown whether VL-9 would survive digestion, reach the bloodstream, and lower blood pressure in living organisms. The IC50 of ~433 µM is relatively high compared to many food-derived ACE inhibitory peptides, which may limit practical potency. No animal or human trials were performed."},{"rthcId":"RPEP-06594","title":"Differential regulation of NPY and SP receptor expression in STRO-1+ve PDLSCs by inflammatory cytokines.","authors":"Winning, Lewis; El Karim, Ikhlas A; Linden, Gerard J; Irwin, Christopher R; Killough, Simon A; Lundy, Fionnuala T","year":2022,"journal":"Journal of periodontal research, 57(1), 186-194","doi":"10.1111/jre.12952","pmid":"34773642","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Inflammatory cytokines up-regulated neuropeptide Y's Y1 receptor and increased ALP activity with neuropeptide Y treatment.","whyItMatters":"Understanding how inflammation affects stem cell behavior can inform treatments for periodontal disease. This research may lead to new therapeutic strategies for enhancing gum tissue regeneration.","specificNumbers":"","methodology":"The study utilized immunomagnetic separation to isolate STRO-1 +ve PDLSCs from healthy teeth and assessed receptor expression and osteogenic effects via gene expression and activity assays.","limitations":"The study was conducted on cells from a single donor, which may limit the generalizability of the findings."},{"rthcId":"RPEP-06595","title":"Alopecia signals associated with calcitonin gene-related peptide inhibitors in the treatment or prophylaxis of migraine: A pharmacovigilance study.","authors":"Woods, Richard H","year":2022,"journal":"Pharmacotherapy, 42(10), 758-767","doi":"10.1002/phar.2725","pmid":"35975575","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Analysis of FDA FAERS data through Q4 2021 revealed:\n\n• 1,827 alopecia cases among 55,994 adverse events reported for CGRP inhibitors (3.26%)\n• Class-wide proportional reporting ratio (PRR): 4.06 (95% CI: 3.88-4.25)\n• By individual drug: fremanezumab PRR 5.42, erenumab PRR 4.29, galcanezumab PRR 4.11, eptinezumab PRR 2.06\n• vs triptans: PRR 12.46 (far more alopecia reports with CGRP inhibitors)\n• vs celecoxib: PRR 3.50\n• vs anticonvulsants, onabotulinumtoxinA, or beta-blockers: no significant disproportionate signal\n• Within the CGRP class: biologic antibodies had PRR 6.11 vs small-molecule CGRP drugs, indicating biologics primarily drive the alopecia signal","whyItMatters":"CGRP plays a role in hair follicle biology and growth cycles, so blocking it could biologically plausibly cause hair loss. With millions of patients now using CGRP inhibitors for migraine prevention, hair loss — even if uncommon — affects a significant absolute number of people. This study provides the first systematic pharmacovigilance evidence supporting the CGRP-alopecia connection and can inform prescriber counseling.","specificNumbers":"","methodology":"Retrospective disproportionality analysis of the FDA Adverse Event Reporting System (FAERS) database through Q4 2021. Thirteen MedDRA preferred terms defined alopecia cases. Proportional reporting ratios (PRR) with 95% confidence intervals were calculated comparing CGRP inhibitors against all other drugs and specific migraine comparators. A PRR >2.0 with lower 95% CI >1.0 and ≥3 cases defined a positive signal.","limitations":"FAERS is a spontaneous reporting system subject to reporting bias, stimulated reporting (media attention on hair loss), and under-reporting. PRR signals indicate disproportionate reporting, not causation. Underlying migraine itself or comorbidities may contribute to hair loss. The analysis cannot determine incidence rates. The comparison drugs have different indications and patient populations, complicating direct comparison. Dose and duration information in FAERS is often incomplete."},{"rthcId":"RPEP-06596","title":"TSG-6 inhibits IL-1β-induced inflammatory responses and extracellular matrix degradation in nucleus pulposus cells by activating the PI3K/Akt signaling pathway.","authors":"Wu, Bing; Guo, Xiaojin; Yan, Xiujie; Tian, Zikai; Jiang, Wei; He, Xin","year":2022,"journal":"Journal of orthopaedic surgery and research, 17(1), 572","doi":"10.1186/s13018-022-03468-9","pmid":"36578051","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"TSG-6 overexpression in IL-1β-stimulated human nucleus pulposus cells produced multiple beneficial effects: it inhibited inflammatory cytokines (TNF-α, IL-8, IL-6), promoted protective extracellular matrix synthesis (increased collagen II and aggrecan, decreased MMP-3), increased sulfated glycosaminoglycan (sGAG) production, and reduced expression of pain-related molecules including CGRP, Substance P, and nerve growth factor.\n\nAll of these effects were mediated through activation of the PI3K/Akt signaling pathway. Both TSG-6 and IL-1β were found to be significantly elevated in degenerated versus normal disc tissue, and IL-1β treatment increased TSG-6 expression in disc cells, suggesting a natural feedback mechanism.","whyItMatters":"Disc degeneration is a leading cause of chronic pain, and current treatments are limited to symptom management or surgery. Finding that TSG-6 can simultaneously reduce inflammation, protect disc structure, and suppress pain signals through a single pathway makes it an attractive therapeutic target. The ability to modulate neuropeptides like CGRP and Substance P — key mediators of disc-related pain — is particularly relevant.","specificNumbers":"","methodology":"Researchers compared TSG-6 and IL-1β expression in normal and degenerated human cervical disc tissue using qRT-PCR and ELISA. Human nucleus pulposus cells were treated with IL-1β (10 ng/mL) and then TSG-6 was overexpressed. Effects on inflammatory markers, extracellular matrix proteins, pain-related molecules, and PI3K/Akt signaling were assessed using qRT-PCR and western blot. sGAG synthesis was also measured.","limitations":"The study was conducted entirely in vitro using cultured human disc cells, which may not fully replicate the complex in vivo disc environment. No animal model or clinical data were presented. The IL-1β concentration used (10 ng/mL) may not reflect physiological levels. TSG-6 overexpression was achieved through artificial means, and therapeutic delivery to disc tissue in vivo would face significant challenges. Long-term effects and dose-response relationships were not explored."},{"rthcId":"RPEP-06597","title":"Synthesis, Self-Assembly, and Cell Responses of Aromatic IKVAV Peptide Amphiphiles.","authors":"Wu, Fang-Yi; Lin, Hsin-Chieh","year":2022,"journal":"Molecules (Basel, Switzerland), 27(13)","doi":"10.3390/molecules27134115","pmid":"35807362","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"PFB-IKVAV increased neuronal marker expression in hMSCs by 4.6 times compared to control.","whyItMatters":"These findings could lead to new materials for regenerative medicine, particularly for nerve repair. Understanding how these peptides work can help develop better treatments for neurological disorders.","specificNumbers":"","methodology":"The study used various spectroscopy techniques to analyze self-assembly and conducted cytotoxicity and differentiation tests on human mesenchymal stem cells.","limitations":"The study primarily focuses on in vitro results, which may not fully translate to in vivo applications. Further research is needed to confirm these findings in living organisms."},{"rthcId":"RPEP-06598","title":"In vitro and in vivo wound healing-promoting activities of phosvitin-derived peptide Pt5-1c.","authors":"Wu, Fei; Gong, Yi; Song, Lili; Li, Haoyi; Zhang, Xiangmin; Li, Hongyan; Zhang, Shicui","year":2022,"journal":"European journal of pharmacology, 920, 174833","doi":"10.1016/j.ejphar.2022.174833","pmid":"35183532","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Pt5-1c accelerated wound closure in fibroblasts and murine models, enhancing healing.","whyItMatters":"Improving wound healing can significantly benefit patients with chronic wounds or injuries. Pt5-1c may offer a new therapeutic option.","specificNumbers":"","methodology":"The study involved in vitro tests on fibroblast scratch wounds and in vivo tests on murine dermal wounds.","limitations":"The study primarily used in vitro and murine models, which may not fully represent human responses."},{"rthcId":"RPEP-06599","title":"Defensins as a promising class of tick antimicrobial peptides: a scoping review.","authors":"Wu, Jiahui; Zhou, Xia; Chen, Qiaoqiao; Chen, Zhiqiang; Zhang, Jinyu; Yang, Lele; Sun, Yuxuan; Wang, Guohui; Dai, Jianfeng; Feng, Tingting","year":2022,"journal":"Infectious diseases of poverty, 11(1), 71","doi":"10.1186/s40249-022-00996-8","pmid":"35725522","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tick defensins are effective against Gram-positive and Gram-negative bacteria, fungi, viruses, and protozoa.","whyItMatters":"Understanding tick defensins could lead to new approaches in managing tick-borne diseases. Their broad-spectrum activity highlights their potential as targets for antimicrobial development.","specificNumbers":"","methodology":"The review analyzed 57 eligible articles from a total of 329 entries found in PubMed and Web of Science.","limitations":"The review is limited to published studies in English and may not cover all relevant research on tick defensins."},{"rthcId":"RPEP-06600","title":"Clinical efficacy of thymosin alpha 1 combined with multi-modality chemotherapy and its effects on immune function of patients with pulmonary tuberculosis complicated with diabetes.","authors":"Wu, Li; Luo, Pei-Pei; Tian, Yan-Hong; Chen, Lai-Yin; Zhang, Yan-Li","year":2022,"journal":"Pakistan journal of medical sciences, 38(1), 179-184","doi":"10.12669/pjms.38.1.4419","pmid":"35035422","tags":["thymosin"],"studyType":"rct","evidenceStrength":"moderate","keyFinding":"Adding thymosin alpha 1 (Tα1) to standard tuberculosis chemotherapy improved outcomes in patients who had both pulmonary TB and diabetes. At 6 months, there was no significant difference between groups. But at 12 months, the Tα1 group had significantly higher rates of sputum culture conversion (clearing the TB bacteria), chest lesion absorption, and lung cavity closure compared to chemotherapy alone (all P<0.05).\n\nThe Tα1 group also showed improved immune function: higher CD3+, CD4+, CD4+/CD8+ ratios, and NK cell levels compared to baseline and controls. Sputum cytokine levels shifted toward less inflammation — higher IL-2 and IFN-γ (pro-immunity), lower IL-4 and TNF-α (pro-inflammation). Adverse drug reactions did not differ between groups.","whyItMatters":"Tuberculosis patients with diabetes have compromised immune systems and often respond poorly to standard TB treatment. Thymosin alpha 1 is an immune-modulating peptide that boosts T-cell function. This trial suggests it can help restore immune competence in these difficult-to-treat patients, improving cure rates without adding side effects — addressing a critical gap in TB management for diabetic patients.","specificNumbers":"n=120 · 60 per group · 12-month follow-up · Improved sputum conversion, lesion absorption, cavity closure (P<0.05 at 12 months) · Increased CD3+, CD4+, NK cells · No difference in adverse events","methodology":"Randomized controlled trial at a single Chinese hospital. 120 patients with pulmonary TB complicated by diabetes were randomized to either thymosin alpha 1 plus standard multi-drug chemotherapy (n=60) or chemotherapy alone (n=60). Outcomes measured at 6 and 12 months included sputum culture conversion, chest lesion absorption, cavity closure, lymphocyte subsets (by flow cytometry), and sputum cytokines (by ELISA).","limitations":"Single-center study at one Chinese hospital, limiting generalizability. The abstract text appears to have a formatting error (\"P0.05\" likely should read \"P<0.05\"), making some statistical details unclear. Blinding is not mentioned, introducing potential bias. The 12-month timeframe may not capture long-term relapse rates. TB treatment outcomes in diabetic patients may differ across populations."},{"rthcId":"RPEP-06601","title":"Association of glucagon-like peptide-1 receptor agonists with cardiac arrhythmias in patients with type 2 diabetes or obesity: a systematic review and meta-analysis of randomized controlled trials.","authors":"Wu, Sijin; Lu, Wenzhao; Chen, Zhongli; Dai, Yan; Chen, Keping; Zhang, Shu","year":2022,"journal":"Diabetology & metabolic syndrome, 14(1), 195","doi":"10.1186/s13098-022-00970-2","pmid":"36572913","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RAs did not significantly increase the risk of arrhythmias (RR 0.97 for AF, RR 0.83 for AFL, RR 1.24 for VAs, RR 0.89 for SCD).","whyItMatters":"Understanding the safety profile of GLP-1 RAs is crucial for patients with diabetes or obesity, especially concerning heart health. This research helps clarify potential cardiovascular risks associated with these treatments.","specificNumbers":"","methodology":"The study conducted a systematic review and meta-analysis of randomized controlled trials comparing GLP-1 RAs to placebo or active controls.","limitations":"The study may not account for long-term effects or specific patient populations, and results may vary based on individual health conditions."},{"rthcId":"RPEP-06602","title":"Effects of Thymosin β4 on Myocardial Apoptosis in Burned Rats.","authors":"Wu, Xiaoming; Li, Shusong; Feng, Xinshu; Wen, Hailing; Meng, Xiangxi; Sun, Kui","year":2022,"journal":"Journal of healthcare engineering, 2022, 2129629","doi":"10.1155/2022/2129629","pmid":"35281544","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Thymosin β4 treatment reduced the apoptosis rate significantly compared to the resuscitation group (P < 0.05).","whyItMatters":"Understanding how thymosin β4 protects heart cells could lead to new treatments for heart damage after severe burns. This research may have implications for improving recovery in burn patients.","specificNumbers":"","methodology":"The study involved 50 rats divided into groups, subjected to burns, and treated with varying doses of thymosin β4, followed by analysis of heart tissue.","limitations":"The study was conducted on rats, which may not fully represent human responses. The sample size is relatively small for broader conclusions."},{"rthcId":"RPEP-06603","title":"Recent progress of dendritic cell-derived exosomes (Dex) as an anti-cancer nanovaccine.","authors":"Xia, Jingyi; Miao, Yangbao; Wang, Xi; Huang, Xiaobing; Dai, Jingying","year":2022,"journal":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 152, 113250","doi":"10.1016/j.biopha.2022.113250","pmid":"35700679","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Dex vaccines have shown better antitumor efficacy in preclinical studies compared to traditional DC vaccines.","whyItMatters":"Understanding the potential of Dex could lead to more effective cancer treatments, addressing current limitations of existing vaccines.","specificNumbers":"","methodology":"The study is a review evaluating existing research on the efficacy of Dex as anticancer vaccines.","limitations":"The clinical efficacy of Dex vaccines remains limited and requires further investigation."},{"rthcId":"RPEP-06604","title":"Electroacupuncture promoted intestinal defensins and rescued the dysbiotic cecal microbiota of high-fat diet-induced obese mice.","authors":"Xia, Xiuwen; Xie, Ya; Gong, Yanju; Zhan, Meng; He, Yan; Liang, Xinyu; Jin, Yue; Yang, Youjun; Ding, Weijun","year":2022,"journal":"Life sciences, 309, 120961","doi":"10.1016/j.lfs.2022.120961","pmid":"36116529","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"EA reduced body weight and fat accumulation while restoring gut microbiota after 21 days.","whyItMatters":"Understanding how electroacupuncture influences gut health could provide new strategies for obesity management. This research highlights the connection between gut microbiota and obesity treatment.","specificNumbers":"","methodology":"The study involved obese mice on a high-fat diet, treated with electroacupuncture for 21 days, followed by microbiota analysis.","limitations":"The study was conducted in mice, and results may not directly translate to humans. Further research is needed to confirm findings in human populations."},{"rthcId":"RPEP-06605","title":"Effects of dulaglutide on endothelial progenitor cells and arterial elasticity in patients with type 2 diabetes mellitus.","authors":"Xie, Dandan; Li, Yutong; Xu, Murong; Zhao, Xiaotong; Chen, Mingwei","year":2022,"journal":"Cardiovascular diabetology, 21(1), 200","doi":"10.1186/s12933-022-01634-1","pmid":"36199064","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Dulaglutide increased EPCs and improved arterial elasticity, with significant changes in nitric oxide and inflammatory markers.","whyItMatters":"Understanding how dulaglutide enhances EPC function could lead to better cardiovascular protection strategies for patients with type 2 diabetes.","specificNumbers":"","methodology":"A randomized controlled trial with 60 patients divided into two groups: one receiving metformin alone and the other metformin plus dulaglutide for 12 weeks.","limitations":"The study's sample size was relatively small, and the results may not be generalizable to all diabetes patients."},{"rthcId":"RPEP-06606","title":"TET3 epigenetically controls feeding and stress response behaviors via AGRP neurons.","authors":"Xie, Di; Stutz, Bernardo; Li, Feng; Chen, Fan; Lv, Haining; Sestan-Pesa, Matija; Catarino, Jonatas; Gu, Jianlei; Zhao, Hongyu; Stoddard, Christopher E; Carmichael, Gordon G; Shanabrough, Marya; Taylor, Hugh S; Liu, Zhong-Wu; Gao, Xiao-Bing; Horvath, Tamas L; Huang, Yingqun","year":2022,"journal":"The Journal of clinical investigation, 132(19)","doi":"10.1172/JCI162365","pmid":"36189793","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Ablation of Tet3 in AGRP neurons caused hyperphagia, obesity, and diabetes in mice.","whyItMatters":"Understanding how TET3 regulates appetite and stress can inform treatments for obesity and related metabolic disorders. This research highlights the complex interplay between feeding behaviors and stress responses.","specificNumbers":"","methodology":"The study utilized CRISPR technology to genetically remove TET3 from AGRP neurons in adult mice and assessed the resulting behavioral and metabolic changes.","limitations":"The study was conducted in mice, so results may not directly apply to humans. Further research is needed to explore TET3's role in human physiology."},{"rthcId":"RPEP-06607","title":"Responsive oligochitosan nano-vesicles with ursodeoxycholic acid and exenatide for NAFLD synergistic therapy via SIRT1.","authors":"Xie, Pengchao; Peng, Yan; Qiu, Liyan","year":2022,"journal":"Carbohydrate polymers, 288, 119388","doi":"10.1016/j.carbpol.2022.119388","pmid":"35450649","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"After one month of treatment, mice showed significant weight recovery and reduced liver lipid contents.","whyItMatters":"NAFLD is a growing health concern worldwide, and effective treatments are urgently needed. This study offers a novel therapeutic strategy that could improve patient outcomes.","specificNumbers":"","methodology":"The study involved synthesizing oligochitosan nano-vesicles, testing their uptake in cultured cells, and conducting in vivo experiments on mice.","limitations":"The study was conducted in mice, and results may not directly translate to humans. Long-term effects and safety need further investigation."},{"rthcId":"RPEP-06608","title":"The Role of Kisspeptin in the Control of the Hypothalamic-Pituitary-Gonadal Axis and Reproduction.","authors":"Xie, Qinying; Kang, Yafei; Zhang, Chenlu; Xie, Ye; Wang, Chuxiong; Liu, Jiang; Yu, Caiqian; Zhao, Hu; Huang, Donghui","year":2022,"journal":"Frontiers in endocrinology, 13, 925206","doi":"10.3389/fendo.2022.925206","pmid":"35837314","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Kisspeptin activates its receptor (KISS1R) to promote GnRH secretion, which in turn controls the entire hypothalamic-pituitary-gonadal axis. Kisspeptin neurons in the arcuate nucleus co-express neurokinin B and dynorphin (forming KNDy neurons) and participate in both positive and negative estrogen feedback to GnRH. In females, kisspeptin regulates follicle development, oocyte maturation, and ovulation. In males, it regulates Leydig cell function, spermatogenesis, sperm function, and reproductive behavior. Mutations in KISS1 or KISS1R genes cause idiopathic hypogonadotropic hypogonadism, central precocious puberty, or female infertility.","whyItMatters":"Kisspeptin sits at the very top of the reproductive hormone cascade. Understanding how it works opens doors to new treatments for infertility, PCOS, delayed puberty, and precocious puberty. Kisspeptin is already being tested as a gentler IVF trigger that avoids the dangerous side effect of ovarian hyperstimulation syndrome.","specificNumbers":"","methodology":"This is a comprehensive narrative review that synthesizes research on kisspeptin's role in the HPG axis, including its signaling pathways, feedback mechanisms, roles in both male and female reproduction, and clinical implications of kisspeptin system disorders.","limitations":"As a review paper, this study does not present original data. Some of the cited research was conducted in animal models, and the translation of kisspeptin-based therapies to clinical practice is still in early stages. The review does not deeply address kisspeptin's roles outside reproduction, such as in metabolism or mood."},{"rthcId":"RPEP-06609","title":"Long-Term Activation of Glucagon-like peptide-1 receptor by Dulaglutide Prevents Diabetic Heart Failure and Metabolic Remodeling in Type 2 Diabetes.","authors":"Xie, Saiyang; Zhang, Min; Shi, Wenke; Xing, Yun; Huang, Yan; Fang, Wen-Xi; Liu, Shi-Qiang; Chen, Meng-Ya; Zhang, Tong; Chen, Si; Zeng, Xiaofeng; Wang, Shasha; Deng, Wei; Tang, Qizhu","year":2022,"journal":"Journal of the American Heart Association, 11(19), e026728","doi":"10.1161/JAHA.122.026728","pmid":"36172969","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In a mouse model of type 2 diabetes (high-fat diet/streptozotocin), 8 weeks of dulaglutide treatment produced multiple cardioprotective effects: it ameliorated insulin resistance, improved glucose tolerance, reduced hyperlipidemia, and promoted fatty acid utilization in the heart muscle.\n\nCritically, dulaglutide attenuated cardiac remodeling and dysfunction by restoring mitochondrial morphology — reversing the mitochondrial fragmentation seen in diabetic hearts. The mechanism was shown to depend on AMPKα2 (AMP-activated protein kinase α2): dulaglutide preserved AMPKα2-dependent mitochondrial homeostasis, and when AMPKα2 was knocked out in mice, dulaglutide's protective cardiac effects were almost completely abolished. These findings were corroborated in neonatal rat heart cells treated with high glucose and palmitic acid.","whyItMatters":"Heart failure is the leading cause of death in people with type 2 diabetes. While clinical trials like REWIND showed that dulaglutide reduces cardiovascular events, this study explains the molecular reason why — mitochondrial rescue through AMPKα2. Understanding this mechanism could help identify which patients will benefit most and lead to more targeted therapies. It also validates the concept of using GLP-1 receptor agonists specifically for diabetic heart protection.","specificNumbers":"","methodology":"Researchers used high-fat diet/streptozotocin-induced type 2 diabetic mice, treated with subcutaneous dulaglutide or vehicle for 8 weeks. Heart function, structure, and metabolic profiles were assessed. Mitochondrial morphology and function were evaluated in cardiac tissue. The mechanism was validated using both in vitro experiments (neonatal rat ventricular myocytes treated with high glucose plus palmitic acid) and AMPKα2 mutant mice to confirm the pathway's necessity.","limitations":"This is a preclinical study using mouse and rat models of diabetes, which don't perfectly replicate human diabetic cardiomyopathy. The 8-week treatment duration is short relative to the chronic nature of diabetic heart disease in humans. While AMPKα2 knockout demonstrated the mechanism's necessity, other protective pathways may also contribute. The mouse model used (HFD/streptozotocin) combines features of type 1 and type 2 diabetes, which may not fully represent either. Specific sample sizes per group were not reported in the abstract."},{"rthcId":"RPEP-06610","title":"Pinocembrin relieves hip fracture-induced pain by repressing spinal substance P signaling in aged rats.","authors":"Xing, Baorui; Feng, Nana; Zhang, Juan; Li, Yunmei; Hou, Xiuxiu; Wu, Hao; Liu, Wendong; Han, Guangpu","year":2022,"journal":"Journal of neurophysiology, 127(2), 397-404","doi":"10.1152/jn.00517.2021","pmid":"34986062","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"PCN treatment reduced pain and inflammation in aged rats with hip fractures, reversing substance P signaling.","whyItMatters":"This research highlights a potential new treatment for managing pain in older adults with hip fractures, a common and debilitating injury. Understanding how PCN works could lead to better pain management strategies.","specificNumbers":"","methodology":"Aged rats with hip fractures were treated with either a vehicle or 80 mg/kg/day of PCN for two weeks, and various pain and inflammation markers were measured.","limitations":"The study was conducted in aged rats, and results may not directly translate to humans. Further research is needed to confirm the findings in clinical settings."},{"rthcId":"RPEP-06611","title":"Marine Products As a Promising Resource of Bioactive Peptides: Update of Extraction Strategies and Their Physiological Regulatory Effects.","authors":"Xing, Lujuan; Wang, Zixu; Hao, Yuejing; Zhang, Wangang","year":2022,"journal":"Journal of agricultural and food chemistry, 70(10), 3081-3095","doi":"10.1021/acs.jafc.1c07868","pmid":"35235313","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Marine bioactive peptides exhibit diverse biological properties including antioxidant and antihypertensive effects.","whyItMatters":"Understanding marine bioactive peptides can lead to new nutritional supplements that may help manage chronic diseases. This research highlights the potential for improving public health through dietary sources.","specificNumbers":"","methodology":"This is a review study summarizing recent advancements in extraction strategies and physiological effects of marine bioactive peptides.","limitations":"As a review, it summarizes existing literature but does not present new experimental data."},{"rthcId":"RPEP-06612","title":"Potential Roles of Glucagon-Like Peptide 1 Receptor Agonists (GLP-1 RAs) in Nondiabetic Populations.","authors":"Xu, Dan; Nair, Ankith; Sigston, Charlie; Ho, Chau; Li, Jia; Yang, Daya; Liao, Xinxue; Chen, Wei; Kuang, Ming; Li, Yanbing; Reid, Christopher; Xiao, Haipeng","year":2022,"journal":"Cardiovascular therapeutics, 2022, 6820377","doi":"10.1155/2022/6820377","pmid":"36474714","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RAs are associated with a 14% lower risk of major cardiovascular events in diabetic patients and a nonsignificant 6% lower risk in nondiabetic patients.","whyItMatters":"Understanding the role of GLP-1 RAs in nondiabetic individuals could lead to new preventative strategies for cardiovascular diseases. This could expand treatment options for at-risk populations.","specificNumbers":"","methodology":"The study is a narrative review that synthesizes findings from various clinical trials and guidelines regarding GLP-1 RA use.","limitations":"The review is based on existing studies, which may not fully represent the effects in nondiabetic populations due to limited direct research."},{"rthcId":"RPEP-06613","title":"Exploring structural features of potent dipeptidyl peptidase IV (DPP-IV) inhibitory peptides derived from tilapia (Oreochromis niloticus) skin gelatin by an integrated approach of multivariate analysis and Gly-Pro-based peptide library.","authors":"Xu, Qiongyao; Zheng, Lin; Huang, Mingtao; Zhao, Mouming","year":2022,"journal":"Food chemistry, 397, 133821","doi":"10.1016/j.foodchem.2022.133821","pmid":"35917789","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Gly-Pro-type peptides with 4 to 9 residues showed IC50 values 2.15 to 10.43 times lower than Gly-Pro-Xaa tripeptides.","whyItMatters":"Understanding the structural features of these peptides can help in developing new treatments for diabetes. The findings may lead to better dietary sources of DPP-IV inhibitors.","specificNumbers":"","methodology":"The study utilized UPLC-MS/MS and multivariate analysis to assess the DPP-IV inhibitory activities of peptides from tilapia skin gelatin hydrolysates.","limitations":"The study primarily focuses on in vitro analysis, and results may not directly translate to human applications."},{"rthcId":"RPEP-06614","title":"Albumin-binding tag derived Exendin-4 analogue for treating hyperglycemia and diabetic complications.","authors":"Xu, Shujuan; Wang, Fang; Li, Hui; Wang, Ya; Fang, Dongzhong","year":2022,"journal":"Bioengineered, 13(3), 4621-4633","doi":"10.1080/21655979.2021.1995993","pmid":"34696658","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"HEX15 improved glucose tolerance and prolonged normoglycemic duration in diabetic mice.","whyItMatters":"This research could lead to more effective treatments for type 2 diabetes and its complications, potentially improving patient outcomes.","specificNumbers":"","methodology":"The study involved designing and screening fusion peptides, followed by in vitro and in vivo tests on diabetic model animals.","limitations":"The study was conducted in animal models, so results may not directly translate to humans."},{"rthcId":"RPEP-06615","title":"Marked increase in tumor transfection with a truncated branched polymer.","authors":"Xu, Songhui; He, Jiaxi; Imtiyaz, Zuha; Agrawal, Atul K; Woodle, Martin C; Mixson, A James","year":2022,"journal":"The journal of gene medicine, 24(1), e3396","doi":"10.1002/jgm.3396","pmid":"34713552","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The H2K4b-14 polyplex was the most effective, enhancing gene expression in tumors.","whyItMatters":"Improving gene delivery systems can enhance the effectiveness of cancer therapies. This research may lead to better treatment options for patients with tumors.","specificNumbers":"","methodology":"The study involved synthesizing various branched peptides and testing their ability to deliver plasmids to tumor models in mice, using techniques like gel retardation and dynamic light scattering.","limitations":"The study was conducted in a mouse model, which may not fully replicate human responses."},{"rthcId":"RPEP-06616","title":"A distinctive ligand recognition mechanism by the human vasoactive intestinal polypeptide receptor 2.","authors":"Xu, Yingna; Feng, Wenbo; Zhou, Qingtong; Liang, Anyi; Li, Jie; Dai, Antao; Zhao, Fenghui; Yan, Jiahui; Chen, Chuan-Wei; Li, Hao; Zhao, Li-Hua; Xia, Tian; Jiang, Yi; Xu, H Eric; Yang, Dehua; Wang, Ming-Wei","year":2022,"journal":"Nature communications, 13(1), 2272","doi":"10.1038/s41467-022-30041-z","pmid":"35477937","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The N-terminal α-helix of VIP2R adopts a unique conformation that stabilizes the ligand interaction, affecting cAMP accumulation.","whyItMatters":"This research enhances our understanding of how peptide receptors function, which is vital for developing new therapies for conditions like pulmonary hypertension and psychiatric disorders.","specificNumbers":"","methodology":"The study utilized cryo-electron microscopy to determine the structure of VIP2R bound to PACAP27 and a stimulatory G protein.","limitations":"The study focuses on a specific receptor and ligand interaction, which may not fully represent all class B1 GPCRs."},{"rthcId":"RPEP-06617","title":"Progress on growth promoting therapies other than growth hormone.","authors":"Xue, Chuqing; Fu, Junfen","year":2022,"journal":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences, 51(4), 515-520","doi":"10.3724/zdxbyxb-2022-0099","pmid":"37202099","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"New therapies like IGF-1 and CNP provide alternatives for treating short stature.","whyItMatters":"These alternative therapies could offer more effective treatment options for children with growth issues, improving their quality of life. Understanding these options is crucial for healthcare providers and families seeking solutions.","specificNumbers":"","methodology":"The article reviews recent advancements in growth-promoting therapies through literature analysis.","limitations":"The review may not cover all recent studies or emerging therapies, and clinical efficacy varies among individual treatments."},{"rthcId":"RPEP-06618","title":"Self-Assembled Nano-Peptide Hydrogels with Human Umbilical Cord Mesenchymal Stem Cell Spheroids Accelerate Diabetic Skin Wound Healing by Inhibiting Inflammation and Promoting Angiogenesis.","authors":"Xue, Junshuai; Sun, Nianfeng; Liu, Yang","year":2022,"journal":"International journal of nanomedicine, 17, 2459-2474","doi":"10.2147/IJN.S363777","pmid":"35669002","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The hydrogel with stem cell spheres healed wounds in 10 days compared to 21 days for controls.","whyItMatters":"This research offers a promising new approach for treating chronic wounds in diabetic patients, potentially improving their quality of life. It highlights the role of innovative biomaterials in regenerative medicine.","specificNumbers":"","methodology":"The study involved creating stem cell spheroids and combining them with nanopeptide hydrogels, which were then transplanted into diabetic mice to assess healing.","limitations":"The study was conducted in a mouse model, which may not fully replicate human responses. Further research is needed to evaluate long-term effects and safety in humans."},{"rthcId":"RPEP-06619","title":"Ultrashort Peptide-Based Hydrogel for the Healing of Critical Bone Defects in Rabbits.","authors":"Yadav, Nitin; Kumar, Utkarsh; Roopmani, Purandhi; Krishnan, Uma Maheswari; Sethuraman, Swaminathan; Chauhan, Meenakshi K; Chauhan, Virander S","year":2022,"journal":"ACS applied materials & interfaces, 14(48), 54111-54126","doi":"10.1021/acsami.2c18733","pmid":"36401830","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The peptide hydrogel resulted in significantly higher bone mineralization and density compared to untreated and matrigel groups.","whyItMatters":"This research could lead to advanced treatments for bone injuries in humans, potentially improving recovery outcomes. The use of peptide hydrogels represents a promising direction in tissue engineering.","specificNumbers":"","methodology":"The study involved creating a peptide hydrogel and testing it in a rabbit model with critical bone defects, assessing outcomes through imaging and cell analysis.","limitations":"The study was conducted in rabbits, and results may not directly translate to humans. Further research is needed to evaluate long-term effects and safety."},{"rthcId":"RPEP-06620","title":"Evaluation of the therapeutic effect of melittin peptide on the ulcerative colitis mouse model.","authors":"Yaghoubi, Atieh; Amel Jamehdar, Saeid; Reza Akbari Eidgahi, Mohammad; Ghazvini, Kiarash","year":2022,"journal":"International immunopharmacology, 108, 108810","doi":"10.1016/j.intimp.2022.108810","pmid":"35569434","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Melittin — a peptide from bee venom — dramatically improved clinical symptoms of ulcerative colitis in a DSS-induced mouse model, both as a standalone treatment and in combination with sulfasalazine (a standard UC drug). The peptide nearly eliminated histological damage in colon tissue and significantly reduced inflammation. Melittin also showed antioxidant effects by restoring the oxidant/antioxidant balance in damaged tissue. When used alongside sulfasalazine, melittin enhanced the conventional drug's therapeutic effect while attenuating its adverse effects.","whyItMatters":"Ulcerative colitis affects millions of people, and current treatments often have inadequate efficacy or significant side effects. This study suggests melittin could serve dual roles: as a standalone anti-inflammatory agent and as a combination partner that boosts the effectiveness of existing drugs while reducing their toxicity. The antioxidant mechanism adds another dimension beyond simple inflammation suppression.","specificNumbers":"","methodology":"C57BL/6 male mice were given dextran sulfate sodium (DSS) in drinking water to induce ulcerative colitis. Mice were then treated with melittin peptide alone, sulfasalazine alone, or the combination. Clinical symptoms (weight loss, stool consistency, bleeding) were monitored. Colon tissue was examined histologically for damage and inflammation. Oxidant/antioxidant balance was assessed in colon tissue.","limitations":"Mouse model of UC (DSS-induced) does not perfectly replicate human ulcerative colitis, which involves autoimmune components. Specific melittin doses were not detailed in the abstract. No toxicity profiling of melittin itself was reported — bee venom peptides can have significant side effects at higher doses. Sample sizes per group were not specified. Short-term study without long-term follow-up."},{"rthcId":"RPEP-06621","title":"A tumor metastasis-associated molecule TWIST1 is a favorable target for cancer immunotherapy due to its immunogenicity.","authors":"Yajima, Yuki; Kosaka, Akemi; Ishibashi, Kei; Yasuda, Shunsuke; Komatsuda, Hiroki; Nagato, Toshihiro; Oikawa, Kensuke; Kitada, Masahiro; Takekawa, Masanori; Kumai, Takumi; Ohara, Kenzo; Ohkuri, Takayuki; Kobayashi, Hiroya","year":2022,"journal":"Cancer science, 113(8), 2526-2535","doi":"10.1111/cas.15429","pmid":"35579200","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The researchers identified TWIST1₁₄₀₋₁₆₂ as an immunogenic peptide sequence within the TWIST1 protein that effectively activated TWIST1-specific CD4+ helper T-cells. Key findings:\n\n- Breast cancer patients showed stronger TWIST1-specific immune responses in short-term culture assays compared to healthy donors, indicating pre-existing immune recognition\n- Vaccination with the TWIST1 peptide in humanized mice efficiently expanded TWIST1-reactive helper T-lymphocytes\n- TWIST1 is upregulated in tumor cells under hypoxia and promotes metastasis — it appears late in tumor progression when the immune-suppressive microenvironment allows its expression despite its immunogenicity\n\nThe study's hypothesis — that highly immunogenic molecules can be expressed by tumors only after establishing immune suppression — provides a rational framework for identifying shared cancer vaccine targets.","whyItMatters":"Most cancer vaccine approaches require identifying unique mutations in each patient's tumor — an expensive and time-consuming process. TWIST1 is a shared antigen expressed across many patients' tumors, meaning a single vaccine could work for many people. Because TWIST1 drives metastasis (the main cause of cancer death), targeting it immunologically could both treat existing disease and prevent cancer spread.","specificNumbers":"","methodology":"TWIST1 peptide sequences were analyzed for immunogenicity. The peptide TWIST1₁₄₀₋₁₆₂ was tested for its ability to activate CD4+ T-cells. T-cell responses were compared between breast cancer patients and healthy donors using short-term culture assays. In vivo vaccination was tested in humanized mice (mice engrafted with human immune systems) to assess TWIST1-reactive helper T-lymphocyte expansion.","limitations":"The study focused primarily on breast cancer patients, so TWIST1 immunogenicity in other cancer types needs confirmation. The humanized mouse model, while valuable, does not fully replicate the human immune system. Long-term vaccination efficacy and actual tumor rejection were not demonstrated. The correlation between TWIST1-specific T-cell responses and clinical outcomes was not assessed. Sample sizes for patient comparisons were not specified."},{"rthcId":"RPEP-06622","title":"A Significant Effect of Oral Semaglutide on Cardiovascular Risk Factors in Patients With Type 2 Diabetes.","authors":"Yanai, Hidekatsu; Hakoshima, Mariko; Adachi, Hiroki; Katsuyama, Hisayuki","year":2022,"journal":"Cardiology research, 13(5), 303-308","doi":"10.14740/cr1441","pmid":"36405226","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Body weight decreased significantly at 3 and 6 months, and systolic blood pressure decreased after 6 months.","whyItMatters":"Improving cardiovascular risk factors in diabetic patients can lead to better health outcomes and reduce the risk of heart-related complications.","specificNumbers":"","methodology":"The study retrospectively analyzed metabolic parameters of 47 patients who took oral semaglutide over a period of 6 months.","limitations":"The study was retrospective and had a small sample size, limiting the generalizability of the findings."},{"rthcId":"RPEP-06623","title":"Construction and Evaluation of Chitosan-Based Nanoparticles for Oral Administration of Exenatide in Type 2 Diabetic Rats.","authors":"Yang, Jian-Miao; Wu, Lin-Jie; Lin, Meng-Ting; Lu, Yi-Ying; Wang, Tian-Tian; Han, Min; Zhang, Bin; Xu, Dong-Hang","year":2022,"journal":"Polymers, 14(11)","doi":"10.3390/polym14112181","pmid":"35683851","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Chitosan/alginate nanoparticles improved oral bioavailability and hypoglycemic effects of exenatide.","whyItMatters":"Improving the oral delivery of therapeutic peptides like exenatide could enhance treatment options for diabetes patients. This research opens avenues for better drug formulations that are easier to administer.","specificNumbers":"","methodology":"The study involved formulating chitosan-based nanoparticles, encapsulating exenatide, and evaluating their effectiveness in diabetic rats.","limitations":"The study was conducted in diabetic rats, and results may not directly translate to humans."},{"rthcId":"RPEP-06624","title":"Nanomolar inhibition of SARS-CoV-2 infection by an unmodified peptide targeting the prehairpin intermediate of the spike protein.","authors":"Yang, Kailu; Wang, Chuchu; Kreutzberger, Alex J B; Ojha, Ravi; Kuivanen, Suvi; Couoh-Cardel, Sergio; Muratcioglu, Serena; Eisen, Timothy J; White, K Ian; Held, Richard G; Subramanian, Subu; Marcus, Kendra; Pfuetzner, Richard A; Esquivies, Luis; Doyle, Catherine A; Kuriyan, John; Vapalahti, Olli; Balistreri, Giuseppe; Kirchhausen, Tom; Brunger, Axel T","year":2022,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 119(40), e2210990119","doi":"10.1073/pnas.2210990119","pmid":"36122200","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The peptide achieves single-digit nanomolar inhibition of SARS-CoV-2.","whyItMatters":"This research is significant as it addresses the urgent need for effective antiviral treatments against evolving SARS-CoV-2 variants. The findings may lead to new therapeutic options that are less susceptible to mutations.","specificNumbers":"","methodology":"The study involved structural analysis of the spike protein and testing the peptide's effectiveness in cell-based and virus-based assays.","limitations":"The study primarily focuses on in vitro results, which may not fully translate to clinical effectiveness in humans."},{"rthcId":"RPEP-06625","title":"Nanomolar inhibition of SARS-CoV-2 infection by an unmodified peptide targeting the pre-hairpin intermediate of the spike protein.","authors":"Yang, Kailu; Wang, Chuchu; Kreutzberger, Alex J B; Ojha, Ravi; Kuivanen, Suvi; Couoh-Cardel, Sergio; Muratcioglu, Serena; Eisen, Timothy J; White, K Ian; Held, Richard G; Subramanian, Subu; Marcus, Kendra; Pfuetzner, Richard A; Esquivies, Luis; Doyle, Catherine A; Kuriyan, John; Vapalahti, Olli; Balistreri, Giuseppe; Kirchhausen, Tomas; Brunger, Axel T","year":2022,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2022.08.11.503553","pmid":"35982670","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Structural studies of the SARS-CoV-2 spike protein HR1HR2 six-helix bundle revealed an extended, well-folded N-terminal region of HR2 that interacts with the HR1 triple helix. Based on this structure:\n\n- An extended HR2 peptide was designed that achieves single-digit nanomolar inhibition in cell-based fusion assays, VSV-SARS-CoV-2 chimera assays, and authentic SARS-CoV-2 infection assays\n- No chemical modifications (lipidation, stapling) were needed\n- The peptide inhibited all major SARS-CoV-2 variants tested\n- ~100-fold more potent than all previously published short, unmodified HR2 peptides\n- Very long inhibition lifetime after washout, suggesting it targets a pre-hairpin intermediate state of the spike protein\n- The N-terminal extension beyond the HR2 helical region proved critical for potency","whyItMatters":"Monoclonal antibody therapies for COVID-19 became useless against Omicron and subsequent variants because they target the rapidly mutating receptor binding domain. This peptide targets the fusion machinery, which is far more conserved because mutations there can prevent the virus from entering cells at all. A simple, unmodified peptide that works against all variants and is cheap to manufacture could be an important addition to the antiviral toolkit — especially for future coronavirus outbreaks.","specificNumbers":"","methodology":"Structural biology (likely X-ray crystallography or cryo-EM) was used to characterize the HR1HR2 six-helix bundle of the SARS-CoV-2 spike protein. Based on the structure, an extended HR2 peptide was designed. Antiviral potency was tested in three assay systems: cell-based membrane fusion assays, VSV-SARS-CoV-2 chimeric virus assays, and authentic SARS-CoV-2 infection assays. Activity was assessed against multiple SARS-CoV-2 variants. Washout experiments tested the duration of inhibition to probe the mechanism of action.","limitations":"This is a preprint (bioRxiv) that has not completed peer review at the time of cataloging. All data is in vitro — no animal or human studies are reported. The peptide's pharmacokinetic properties (stability in blood, half-life, tissue distribution) are not addressed. Route of administration for therapeutic use is unclear — peptides typically require injection. Manufacturing scalability, while theoretically simpler without modifications, still needs validation. In vivo efficacy may differ from cell-based assays."},{"rthcId":"RPEP-06626","title":"Co-encapsulation of Egg-White-Derived Peptides (EWDP) and Curcumin within the Polysaccharide-Based Amphiphilic Nanoparticles for Promising Oral Bioavailability Enhancement: Role of EWDP.","authors":"Yang, Meng; Liu, Jingbo; Li, Yajuan; Yang, Qi; Liu, Chunmei; Liu, Xuanting; Zhang, Biying; Zhang, Hui; Zhang, Ting; Du, Zhiyang","year":2022,"journal":"Journal of agricultural and food chemistry, 70(16), 5126-5136","doi":"10.1021/acs.jafc.1c08186","pmid":"35412315","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The co-encapsulation of EWDP and curcumin resulted in over 20% increase in antioxidant activity and bioaccessibility.","whyItMatters":"Enhancing the bioavailability of nutraceuticals like curcumin can lead to more effective dietary supplements and therapeutic applications. This research opens new avenues for improving nutrient delivery systems.","specificNumbers":"","methodology":"The study involved fabricating amphiphilic nanoparticles and testing their properties regarding solubility, stability, and absorption in a controlled environment.","limitations":"The study was conducted in vitro, and results may not directly translate to human applications."},{"rthcId":"RPEP-06627","title":"Heat-inactivated modified vaccinia virus Ankara boosts Th1 cellular and humoral immunity as a vaccine adjuvant.","authors":"Yang, Ning; Garcia, Aitor; Meyer, Cindy; Tuschl, Thomas; Merghoub, Taha; Wolchok, Jedd D; Deng, Liang","year":2022,"journal":"NPJ vaccines, 7(1), 120","doi":"10.1038/s41541-022-00542-5","pmid":"36261460","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Heat-iMVA improved T cell and antibody responses, extending survival and delaying tumor growth.","whyItMatters":"Enhancing immune responses in vaccines is crucial for effective cancer and COVID-19 treatments. Heat-iMVA could lead to more effective vaccines.","specificNumbers":"","methodology":"The study employed a therapeutic vaccination model using tumor neoantigen peptide vaccines and SARS-CoV-2 spike protein to assess the adjuvant effects of heat-iMVA.","limitations":"The study primarily focuses on preclinical models, and results may not directly translate to human applications."},{"rthcId":"RPEP-06628","title":"Peptide-Based Bioconjugates and Therapeutics for Targeted Anticancer Therapy.","authors":"Yang, Seong-Bin; Banik, Nipa; Han, Bomin; Lee, Dong-Nyeong; Park, Jooho","year":2022,"journal":"Pharmaceutics, 14(7)","doi":"10.3390/pharmaceutics14071378","pmid":"35890274","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Emerging peptide-based therapeutics show excellent efficacy in targeted cancer therapy.","whyItMatters":"These findings could lead to more effective and safer cancer treatments. Improved targeting may reduce side effects compared to traditional therapies.","specificNumbers":"","methodology":"This is a review study analyzing recent advancements in peptide-based biomedicines and their applications in cancer therapy.","limitations":"As a review, it summarizes existing research without presenting new experimental data."},{"rthcId":"RPEP-06629","title":"Aligned fibrin/functionalized self-assembling peptide interpenetrating nanofiber hydrogel presenting multi-cues promotes peripheral nerve functional recovery.","authors":"Yang, Shuhui; Zhu, Jinjin; Lu, Changfeng; Chai, Yi; Cao, Zheng; Lu, Jiaju; Zhang, Zhe; Zhao, He; Huang, Yin-Yuan; Yao, Shenglian; Kong, Xiangdong; Zhang, Peixun; Wang, Xiumei","year":2022,"journal":"Bioactive materials, 8, 529-544","doi":"10.1016/j.bioactmat.2021.05.056","pmid":"34541418","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The AFG/fSAP hydrogel bridged a 15-mm sciatic nerve gap in rats and improved functional recovery.","whyItMatters":"This research offers a new approach to nerve repair that could enhance recovery outcomes for patients with peripheral nerve injuries. It may provide an alternative to traditional nerve grafts, which have limitations.","specificNumbers":"","methodology":"The study involved creating a hydrogel through electrospinning and molecular self-assembly, followed by in vitro and in vivo testing in rats.","limitations":"The study was conducted in rats, and results may not directly translate to humans. Long-term effects and safety in humans remain to be evaluated."},{"rthcId":"RPEP-06630","title":"A Collagen-Derived Oligopeptide from Salmo salar Collagen Hydrolysates Restrains Atherogenesis in ApoE-/- Mice via Targeting P2 Y12 Receptor.","authors":"Yang, Yijie; Liu, Hui; Cui, Liyuan; Liu, Yibo; Fu, Lulu; Li, Bo","year":2022,"journal":"Molecular nutrition & food research, 66(13), e2200166","doi":"10.1002/mnfr.202200166","pmid":"35490399","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The salmon collagen-derived peptide OGEFG (OG-5) inhibited platelet aggregation by antagonizing P2Y12 receptors, reduced tail thrombosis by 30% in a dose-dependent manner, and significantly reduced atherosclerotic plaque formation in ApoE-/- mice — with effects comparable to aspirin and no side effects. Molecular docking showed strong binding to P2Y12 receptors (-10.70 kcal/mol). OG-5 also inhibited inflammatory cytokine release and vascular smooth muscle cell migration in vitro.","whyItMatters":"Antiplatelet drugs like aspirin and clopidogrel (which targets P2Y12) are cornerstones of cardiovascular disease prevention but carry bleeding risks. A food-derived peptide that targets the same P2Y12 receptor with comparable anti-atherosclerotic effects and no observed side effects could represent a safer preventive approach for cardiovascular disease.","specificNumbers":"30% reduction in tail thrombosis · -10.70 kcal/mol binding energy to P2Y12 · comparable effect to aspirin · no side effects in long-term administration","methodology":"The 5-amino acid peptide OGEFG was tested for antiplatelet activity via aggregation assays (especially ADP-induced), P2Y12 receptor binding via molecular docking, and downstream signaling (PI3K-Akt and cAMP-VASP pathways). In vitro assays measured inflammatory cytokine release and smooth muscle cell migration. Long-term in vivo administration in ApoE-/- atherosclerosis mice compared plaque formation against aspirin control.","limitations":"ApoE-/- mice are a standard atherosclerosis model but don't perfectly replicate human disease. Oral bioavailability and digestive stability of the peptide in humans are unknown. The aspirin comparison is qualitative — specific dosing equivalence was not established. Human clinical trials are needed to confirm safety and efficacy."},{"rthcId":"RPEP-06631","title":"GLP-1 receptor agonist-associated tumor adverse events: A real-world study from 2004 to 2021 based on FAERS.","authors":"Yang, Zheng; Lv, Yuhuan; Yu, Meng; Mei, Mei; Xiang, Linyu; Zhao, Subei; Li, Rong","year":2022,"journal":"Frontiers in pharmacology, 13, 925377","doi":"10.3389/fphar.2022.925377","pmid":"36386208","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"8718 GLP-1RA-associated tumors were reported, with significant signals for thyroid and pancreatic cancers.","whyItMatters":"Understanding the potential risks associated with GLP-1RAs is crucial for patient safety, especially given their widespread use in diabetes management. This research provides valuable insights for clinicians regarding the monitoring of tumor-related adverse effects.","specificNumbers":"","methodology":"The study utilized disproportionality analysis on FAERS data from 2004 to 2021 to assess the relationship between GLP-1RAs and tumor occurrences.","limitations":"The study relies on reported data, which may be subject to underreporting or misclassification of cases."},{"rthcId":"RPEP-06632","title":"Conjugation of a Cationic Cell-Penetrating Peptide with a Novel Kunitzin-like Trypsin Inhibitor: New Insights for Enhancement of Peptide Bioactivities.","authors":"Yao, Junting; Yin, Weining; Chen, Yuqing; Chen, Xiaoling; Jiang, Yangyang; Wang, Tao; Ma, Chengbang; Zhou, Mei; Chen, Tianbao; Shaw, Chris; Wang, Lei","year":2022,"journal":"Pharmaceutics, 14(9)","doi":"10.3390/pharmaceutics14091805","pmid":"36145553","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Conjugating the cell-penetrating TAT peptide to a frog-derived trypsin inhibitor (kunitzin-OV2) produced dramatic improvements: 32-fold increased antibacterial activity against E. coli and new antiproliferative activity against cancer cells that the original peptide lacked. A phenylalanine-substituted variant (TAT-F9-KOV2) showed 20-25 fold greater antiproliferative activity against lung cancer cells and was also active against breast cancer and glioblastoma lines. The CPP conjugation solved the cell penetration barrier without increasing membrane lysis.","whyItMatters":"Many bioactive peptides from nature can't enter cells, severely limiting their therapeutic potential. This study shows that simply attaching a cell-penetrating peptide can unlock entirely new biological activities — transforming a weak antibacterial into a potent one and revealing previously hidden anticancer properties. This approach could be applied to unlock the full potential of thousands of known bioactive peptides.","specificNumbers":"32-fold increase in antibacterial activity · 20-25 fold increase in antiproliferative activity vs lung cancer · active against MCF-7, U251MG, H157, H460 cancer lines · no increased membrane lysis","methodology":"Novel kunitzin-OV2 peptide and its phenylalanine-substituted analog were synthesized and conjugated to the TAT cell-penetrating peptide. In vitro assays measured trypsin/chymotrypsin inhibition, antibacterial activity (E. coli), cell penetration capability, membrane lysis, and antiproliferative activity against four cancer cell lines (breast MCF-7, glioblastoma U251MG, lung H157 and H460).","limitations":"Entirely in vitro — no in vivo testing of efficacy, toxicity, or pharmacokinetics. The TAT peptide may trigger immune responses in vivo. Selectivity between cancer and normal cells was not assessed. Mechanism of antiproliferative activity (beyond cell penetration) not fully elucidated."},{"rthcId":"RPEP-06633","title":"Phase II Adjuvant Cancer-specific Vaccine Therapy for Esophageal Cancer Patients Curatively Resected After Preoperative Therapy With Pathologically Positive Nodes; Possible Significance of Tumor Immune Microenvironment in its Clinical Effects.","authors":"Yasuda, Takushi; Nishiki, Kohei; Hiraki, Yoko; Kato, Hiroaki; Iwama, Mitsuru; Shiraishi, Osamu; Yasuda, Atsushi; Shinkai, Masayuki; Kimura, Yutaka; Sukegawa, Yasushi; Chiba, Yasutaka; Imano, Motohiro; Takeda, Kazuyoshi; Satou, Takao; Shiozaki, Hitoshi; Nakamura, Yusuke","year":2022,"journal":"Annals of surgery, 275(1), e155-e162","doi":"10.1097/SLA.0000000000003880","pmid":"33055588","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The vaccine group achieved a 5-year esophageal cancer-specific survival (ECSS) of 60.0% compared to 32.4% in the control group (P = 0.045). While relapse-free survival did not reach statistical significance (5-year RFS: 45.3% vs 32.5%), the recurrence rate significantly decreased with the number of peptide antigens that successfully induced antigen-specific cytotoxic T lymphocytes, suggesting a dose-response relationship in immune activation.\n\nThe survival benefit was most pronounced in patients whose tumors were CD8+ and PD-L1 double negative: vaccinated patients in this subgroup achieved 68.0% 5-year ECSS versus only 17.7% in controls (P = 0.010). This suggests the tumor immune microenvironment strongly influences peptide vaccine effectiveness.","whyItMatters":"Esophageal squamous cell cancer with lymph node involvement has one of the worst prognoses in oncology, and there are limited adjuvant treatment options after surgery. This peptide vaccine nearly doubled 5-year cancer-specific survival in a patient population where the expected survival rate is around 30%. The identification of tumor immune microenvironment markers that predict response could enable patient selection, moving toward precision immunotherapy.","specificNumbers":"","methodology":"This was a non-randomized prospective phase II clinical trial (UMIN000003557). Esophageal squamous cell carcinoma patients with pathologically positive lymph nodes after curative resection following preoperative therapy were allocated to vaccine or control groups based on their HLA-A status (HLA-A*24 positive patients received the vaccine). The vaccine consisted of 1 mg each of three tumor-specific epitope peptides (upregulated lung cancer 10, CDCA1, and KIAA0101), injected subcutaneously 10 times weekly then 10 times biweekly. Primary endpoint was relapse-free survival; secondary endpoint was ECSS.","limitations":"This was a non-randomized trial with allocation based on HLA-A status, introducing potential selection bias between groups. The sample size of 63 patients is small for drawing definitive survival conclusions. The primary endpoint (relapse-free survival) did not reach statistical significance; only the secondary endpoint (cancer-specific survival) was significant. Subgroup analyses in small trials carry a high risk of false-positive findings. Phase III randomized confirmation is essential before clinical adoption."},{"rthcId":"RPEP-06634","title":"The mitochondrial-derived peptide MOTS-c relieves hyperglycemia and insulin resistance in gestational diabetes mellitus.","authors":"Yin, Yadong; Pan, Yihui; He, Jin; Zhong, Hong; Wu, Yangyang; Ji, Chenbo; Liu, Lan; Cui, Xianwei","year":2022,"journal":"Pharmacological research, 175, 105987","doi":"10.1016/j.phrs.2021.105987","pmid":"34798268","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06635","title":"Exercise, Mitohormesis, and Mitochondrial ORF of the 12S rRNA Type-C (MOTS-c).","authors":"Yoon, Tae Kwan; Lee, Chan Hee; Kwon, Obin; Kim, Min-Seon","year":2022,"journal":"Diabetes & metabolism journal, 46(3), 402-413","doi":"10.4093/dmj.2022.0092","pmid":"35656563","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Exercise increases MOTS-c levels in muscles and circulation, enhancing performance and metabolism.","whyItMatters":"Understanding how exercise influences mitochondrial peptides can lead to better strategies for improving metabolic health and combating obesity.","specificNumbers":"","methodology":"This is a review study summarizing existing research on exercise, mitohormesis, and MOTS-c.","limitations":"As a review, it synthesizes existing studies but does not present new experimental data."},{"rthcId":"RPEP-06636","title":"Efficacy and safety of dulaglutide compared with the first-line hypoglycemic drugs in Asian patients with type 2 diabetes: a systematic review and meta-analysis.","authors":"Yu, Bin; Lin, Fei; Wang, Maoru; Ning, Hong; Ling, Baodong; Rao, Youyi","year":2022,"journal":"Scientific reports, 12(1), 18281","doi":"10.1038/s41598-022-22263-4","pmid":"36316432","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Dulaglutide 0.75 mg reduced HbA1c by 0.20 and 1.5 mg reduced it by 0.49.","whyItMatters":"Understanding the efficacy and safety of dulaglutide can help optimize diabetes treatment for Asian patients. This research highlights the need for careful monitoring of side effects.","specificNumbers":"","methodology":"The study involved a systematic review and meta-analysis of 4 randomized controlled trials and 1 observational study.","limitations":"The study suggests the need for more high-quality randomized controlled trials to confirm findings and assess long-term safety."},{"rthcId":"RPEP-06637","title":"GLP-1 receptor agonists in diabetic kidney disease: current evidence and future directions.","authors":"Yu, Ji Hee; Park, So Young; Lee, Da Young; Kim, Nan Hee; Seo, Ji A","year":2022,"journal":"Kidney research and clinical practice, 41(2), 136-149","doi":"10.23876/j.krcp.22.001","pmid":"35391537","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Multiple cardiovascular outcome trials have demonstrated that GLP-1 receptor agonists provide renal protective effects in patients with type 2 diabetes beyond their glucose-lowering action. The kidney benefits come through two pathways:\n\n- Direct effects on the kidney: inhibition of oxidative stress and inflammation, and induction of natriuresis (increased sodium excretion in urine)\n- Indirect effects: reduction of conventional DKD risk factors including blood glucose, blood pressure, and body weight\n\nEarly evidence from dual and triple receptor combination agents (targeting GIP, glucagon, and GLP-1 receptors simultaneously) suggests even greater potential for this drug class in treating DKD.","whyItMatters":"Diabetic kidney disease affects roughly 40% of diabetes patients and is a leading cause of kidney failure worldwide. Finding drugs that protect the kidneys while also managing diabetes simplifies treatment and improves outcomes. GLP-1 receptor agonists are uniquely positioned because they address multiple disease drivers simultaneously — glucose, weight, blood pressure, and direct kidney inflammation.","specificNumbers":"","methodology":"This is a narrative review synthesizing evidence from cardiovascular outcome trials (CVOTs) involving GLP-1 receptor agonists in type 2 diabetes patients. The authors compiled clinical trial data on cardiorenal outcomes alongside mechanistic studies explaining how GLP-1 RAs protect the kidney.","limitations":"This is a narrative review, not a systematic review or meta-analysis, so the evidence synthesis may not be comprehensive. The abstract does not report specific effect sizes or kidney-specific endpoints from the CVOTs. Most evidence comes from cardiovascular outcome trials where kidney outcomes were secondary endpoints, not dedicated kidney trials. The dual and triple agonist data referenced is described as 'early evidence.'"},{"rthcId":"RPEP-06638","title":"Neoantigen-reactive T cells exhibit effective anti-tumor activity against colorectal cancer.","authors":"Yu, Yaojun; Zhang, Jing; Ni, Leyi; Zhu, Yuesheng; Yu, Hejie; Teng, Yangyang; Lin, Limiao; Xue, Zhanxiong; Xue, Xiangyang; Shen, Xian; Song, Haiping; Su, Xiaoping; Sun, Weihong; Cai, Zhenzhai","year":2022,"journal":"Human vaccines & immunotherapeutics, 18(1), 1-11","doi":"10.1080/21645515.2021.1891814","pmid":"33689574","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Neoantigen-reactive T cells inhibited tumor growth in mouse models after vaccination.","whyItMatters":"Understanding neoantigens can enhance the effectiveness of immunotherapies for colorectal cancer, potentially leading to personalized treatment options.","specificNumbers":"","methodology":"The study utilized whole-exome and transcriptome sequencing to identify neoantigens and assessed their immunogenicity in patient-derived T cells and mouse models.","limitations":"The study primarily involved mouse models, which may not fully replicate human responses to neoantigen therapies."},{"rthcId":"RPEP-06639","title":"Effect of glucagon-like peptide 1 receptor agonists on albuminuria in adult patients with type 2 diabetes mellitus: A systematic review and meta-analysis.","authors":"Yuan, Daniel; Sharma, Harman; Krishnan, Anirudh; Vangaveti, Venkat N; Malabu, Usman H","year":2022,"journal":"Diabetes, obesity & metabolism, 24(9), 1869-1881","doi":"10.1111/dom.14776","pmid":"35589615","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06640","title":"Bioactive peptides of plant origin: distribution, functionality, and evidence of benefits in food and health.","authors":"Yuan, Hemao; Luo, Zisheng; Ban, Zhaojun; Reiter, Russel J; Ma, Quan; Liang, Ze; Yang, Mingyi; Li, Xihong; Li, Li","year":2022,"journal":"Food & function, 13(6), 3133-3158","doi":"10.1039/d1fo04077d","pmid":"35244644","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Plant-derived peptides exhibit antioxidant, cholesterol-lowering, and antihypertensive activities.","whyItMatters":"Understanding plant-derived peptides can lead to new health products, but more research is crucial to validate their benefits.","specificNumbers":"","methodology":"The review summarizes current extraction, separation, and analytical techniques for plant-derived peptides.","limitations":"The review highlights the lack of extensive clinical trials to support health claims of plant-derived peptides."},{"rthcId":"RPEP-06641","title":"Identification, molecular docking, and kinetic studies of six novel angiotensin-I-converting enzyme (ACE) inhibitory peptides derived from Kenaf (Hibiscus cannabinus L.) seed.","authors":"Zaharuddin, Nurul Dhania; Barkia, Ines; Wan Ibadullah, Wan Zunairah; Zarei, Mohammad; Saari, Nazamid","year":2022,"journal":"International journal of biological macromolecules, 220, 1512-1522","doi":"10.1016/j.ijbiomac.2022.09.142","pmid":"36126810","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Optimized hydrolysis of kenaf seed protein (65°C, pH 6.5, 2.25 hours, E/S ratio 0.03) achieved 55.28% degree of hydrolysis and 75.51% ACE inhibitory activity. The <2 kDa and 2-5 kDa peptide fractions showed the highest activity (82.27% and 83.69% respectively).\n\nSix novel ACE-inhibitory peptides were identified from the 2-5 kDa fraction by QTOF LC-MS: LYWSYLYN, ALFYWVS, LLLHAL, AKSCVVFP, INPPSTTN, and WTIPTPS. Kinetic studies revealed LYWSYLYN had the highest Michaelis constant (Km) and maximum velocity (Vmax) values with the lowest inhibitor constant (Ki), confirming it as the most potent ACE inhibitor among the six peptides.","whyItMatters":"ACE inhibitor drugs are among the most prescribed medications for hypertension, but they can cause side effects like dry cough and angioedema. Food-derived bioactive peptides offer a potential natural complement or alternative. Kenaf seeds are an underutilized protein source, and identifying specific ACE-inhibitory peptides from them could support the development of functional foods, nutraceuticals, or novel antihypertensive agents from sustainable plant sources.","specificNumbers":"","methodology":"Kenaf seed protein was enzymatically hydrolyzed under conditions optimized by response surface methodology (RSM). The hydrolysates were fractionated by molecular weight. ACE inhibitory activity was measured for each fraction. Peptides in the most active fraction (2-5 kDa) were identified using Quadrupole-Time-of-Flight Liquid Chromatography-Mass Spectrometry (QTOF LC-MS). Molecular docking simulations modeled peptide-ACE interactions, and enzyme kinetic studies characterized the inhibition mechanisms.","limitations":"All results are in vitro — the peptides have not been tested in animals or humans for actual blood pressure-lowering effects. Bioactive peptides may be degraded by gastrointestinal enzymes before reaching the bloodstream, so in vitro ACE inhibition may not translate to in vivo efficacy. The stability, bioavailability, and safety of these specific peptides are unknown. Molecular docking provides computational predictions that need experimental validation."},{"rthcId":"RPEP-06642","title":"Inhibition kinetics, molecular docking, and stability studies of the effect of papain-generated peptides from palm kernel cake proteins on angiotensin-converting enzyme (ACE).","authors":"Zarei, Mohammad; Ghanbari, Raheleh; Zainal, Najib; Ovissipour, Reza; Saari, Nazamid","year":2022,"journal":"Food chemistry. Molecular sciences, 5, 100147","doi":"10.1016/j.fochms.2022.100147","pmid":"36573107","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Peptide YGIKVGYAIP had the lowest Ki value of 0.054 mM, indicating strong ACE inhibition.","whyItMatters":"Understanding how these peptides interact with ACE could lead to natural treatments for hypertension. This research highlights the potential of plant-derived compounds in managing blood pressure.","specificNumbers":"","methodology":"The study involved stability testing, inhibition kinetics, and molecular docking of peptides derived from palm kernel cake proteins.","limitations":"The study primarily focuses on in vitro results, which may not directly translate to in vivo effects in humans."},{"rthcId":"RPEP-06643","title":"Involvement of Opioid Peptides in the Analgesic Effect of Spinal Cord Stimulation in a Rat Model of Neuropathic Pain.","authors":"Zhai, Fu-Jun; Han, Song-Ping; Song, Tian-Jia; Huo, Ran; Lan, Xing-Yu; Zhang, Rong; Han, Ji-Sheng","year":2022,"journal":"Neuroscience bulletin, 38(4), 403-416","doi":"10.1007/s12264-022-00844-7","pmid":"35397112","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The analgesic effect of SCS increased with stimulation intensity between 20% and 80% motor thresholds. All tested frequencies (2, 15, 50, 100, 10,000 Hz, and alternating 2/100 Hz) were similarly effective at reducing pain.\n\nCritically, different frequencies operated through distinct opioid peptide mechanisms: 2 Hz SCS significantly increased methionine enkephalin in cerebrospinal fluid and its effect was blocked by mu or kappa opioid receptor antagonists. 100 Hz SCS was blocked only by a kappa antagonist. 10 kHz SCS was blocked by antagonists at any of the three opioid receptor types (mu, delta, or kappa). No tolerance developed within 24 hours of continuous stimulation.","whyItMatters":"Spinal cord stimulation is already used clinically for chronic pain, but programming it has been somewhat empirical. This study reveals that the device literally triggers the body's own painkilling peptide system — and that different settings activate different branches of that system. This mechanistic insight could help clinicians choose optimal stimulation parameters for individual patients, potentially improving outcomes for the millions of people living with chronic neuropathic pain without relying on opioid medications.","specificNumbers":"","methodology":"Researchers used a spared nerve injury model in rats to create neuropathic pain. They then applied spinal cord stimulation at various intensities (20-80% of motor threshold) and frequencies (2 Hz to 10 kHz, plus dense-dispersed patterns). Pain sensitivity was measured using mechanical withdrawal thresholds. To determine the opioid mechanisms involved, specific opioid receptor antagonists (for mu, delta, and kappa receptors) were administered before SCS. Methionine enkephalin levels were measured in cerebrospinal fluid using radioimmunoassay.","limitations":"This study was conducted entirely in rats, and the neuropathic pain model (spared nerve injury) may not fully replicate the complexity of human chronic pain conditions. The 24-hour tolerance assessment is relatively short — longer-term tolerance effects remain unknown. Specific opioid peptide measurements were only performed for methionine enkephalin at 2 Hz; the peptides mediating effects at other frequencies were inferred from antagonist experiments rather than directly measured. Translation to human SCS programming requires clinical validation."},{"rthcId":"RPEP-06644","title":"Molecular insights into the distinct signaling duration for the peptide-induced PTH1R activation.","authors":"Zhai, Xiuwen; Mao, Chunyou; Shen, Qingya; Zang, Shaokun; Shen, Dan-Dan; Zhang, Huibing; Chen, Zhaohong; Wang, Gang; Zhang, Changming; Zhang, Yan; Liu, Zhihong","year":2022,"journal":"Nature communications, 13(1), 6276","doi":"10.1038/s41467-022-34009-x","pmid":"36271004","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"PTH-bound PTH1R-Gs complexes show less motion and greater mutation tolerance than ABL-bound complexes.","whyItMatters":"Understanding the distinct signaling mechanisms of these peptides can inform the development of better therapeutic strategies for bone-related diseases.","specificNumbers":"","methodology":"The study utilized cryo-electron microscopy, 3D variability analysis, and site-directed mutagenesis to investigate receptor structures and signaling.","limitations":"The study primarily focuses on structural analysis and may not fully capture the in vivo complexities of receptor signaling."},{"rthcId":"RPEP-06645","title":"Recombinant Human Thymosin β4 (rhTβ4) Modulates the Anti-Inflammatory Responses to Alleviate Benzalkonium Chloride (BAC)-Induced Dry Eye Disease.","authors":"Zhai, Yanfang; Zheng, Xiaoxiang; Mao, Yunyun; Li, Kai; Liu, Yanhong; Gao, Yuemei; Zhao, Mengsu; Yang, Rui; Yu, Rui; Chen, Wei","year":2022,"journal":"International journal of molecular sciences, 23(10)","doi":"10.3390/ijms23105458","pmid":"35628276","tags":["thymosin-beta-4"],"studyType":"Animal Study (Mouse Model)","evidenceStrength":"early-stage","keyFinding":"Thymosin beta-4 (Tβ4) eye drops at both 0.05% and 0.1% concentrations improved all clinical measures of dry eye disease in mice within 7 days. The peptide increased tear production, reduced corneal staining (a measure of surface damage), restored goblet cells in the conjunctiva (which produce the protective mucus layer), and reduced cell death in the cornea and conjunctiva.\n\nThe mechanism was anti-inflammatory: Tβ4 reduced inflammatory cytokine levels and CD4+ T cell infiltration by blocking NF-κB activation — the master inflammatory switch. Both doses were effective.","whyItMatters":"Dry eye disease affects hundreds of millions of people globally and current treatments are limited. Tβ4 is unique because it simultaneously addresses multiple aspects of dry eye: it reduces inflammation, protects cells from death, and restores the goblet cells that produce the eye's protective mucus coating. This multi-mechanism approach could be more effective than current single-target therapies like cyclosporine or lifitegrast.","specificNumbers":"0.05% and 0.1% rhTβ4 · 7-day treatment · increased tear volume · reduced corneal staining · increased goblet cells · reduced CD4+ T cells · blocked NF-κB","methodology":"Dry eye was induced in mice using benzalkonium chloride (BAC), a chemical preservative that damages the ocular surface. Mice received eye drops containing 0.05% or 0.1% recombinant human Tβ4 for 7 days. Researchers measured tear volume, corneal staining scores, goblet cell counts (PAS staining), CD4+ T cell infiltration (immunohistochemistry), cell death (TUNEL assay), inflammatory cytokines (qRT-PCR and ELISA), and NF-κB activation.","limitations":"Mouse model only — human dry eye is a chronic condition with different underlying causes than chemically-induced mouse DED. The 7-day treatment period is short. No comparison to existing dry eye treatments (cyclosporine, lifitegrast). The BAC model may not capture all aspects of human dry eye. Specific statistical values and sample sizes are not provided in the abstract."},{"rthcId":"RPEP-06646","title":"Gut-innervating nociceptors regulate the intestinal microbiota to promote tissue protection.","authors":"Zhang, Wen; Lyu, Mengze; Bessman, Nicholas J; Xie, Zili; Arifuzzaman, Mohammad; Yano, Hiroshi; Parkhurst, Christopher N; Chu, Coco; Zhou, Lei; Putzel, Gregory G; Li, Ting-Ting; Jin, Wen-Bing; Zhou, Jordan; Hu, Hongzhen; Tsou, Amy M; Guo, Chun-Jun; Artis, David","year":2022,"journal":"Cell, 185(22), 4170-4189.e20","doi":"10.1016/j.cell.2022.09.008","pmid":"36240781","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Silencing TRPV1+ nociceptors (pain-sensing neurons) in the gut through three different methods — chemogenetic silencing, adenoviral colon-specific silencing, and pharmacological ablation — all resulted in more severe intestinal inflammation and impaired tissue repair in mouse models.\n\nThe disruption of nociception caused significant alterations in gut microbiota composition, producing a transmissible dysbiosis (meaning the disrupted microbiome could transfer disease susceptibility). Mono-colonization of germ-free mice with Gram-positive Clostridium species promoted tissue protection through a nociceptor-dependent pathway. Mechanistically, silencing nociceptors decreased levels of substance P, and therapeutic delivery of substance P restored tissue-protective effects in a microbiota-dependent manner. Analysis of intestinal biopsies from IBD patients showed dysregulated nociceptor gene expression, suggesting clinical relevance.","whyItMatters":"This study reveals an entirely new role for pain-sensing nerves in the gut — they are not just passive detectors of inflammation but active participants in maintaining gut health. The finding that substance P, a well-known neuropeptide, mediates this protection through the microbiome opens a new therapeutic concept for inflammatory bowel diseases. It also raises important cautions about pain-blocking treatments that might inadvertently worsen gut inflammation.","specificNumbers":"","methodology":"The researchers used multiple complementary approaches in mice: chemogenetic silencing (designer receptors to selectively deactivate neurons), adenoviral-mediated colon-specific silencing, and pharmacological ablation of TRPV1+ nociceptors. They studied the effects on a murine model of intestinal damage and inflammation, measuring inflammation severity, tissue repair, and microbiome composition. Germ-free mouse experiments and mono-colonization with specific bacteria tested the microbiome's role. Substance P delivery experiments tested the mechanistic pathway. Human IBD patient biopsies were analyzed for nociceptor gene expression.","limitations":"The core experiments were conducted in mice, and the complex interplay between nociceptors, substance P, and the microbiome may differ in humans. The human component was limited to gene expression analysis in biopsies, not functional validation. The therapeutic delivery of substance P was performed in a controlled experimental setting, and the feasibility, dosing, and safety of substance P therapy in humans with IBD are unknown. Long-term effects of nociceptor modulation on gut health were not assessed."},{"rthcId":"RPEP-06647","title":"A novel synthetic peptide SVHRSP attenuates dopaminergic neurodegeneration by inhibiting NADPH oxidase-mediated neuroinflammation in experimental models of Parkinson's disease.","authors":"Zhang, Xiaomeng; Tu, Dezhen; Li, Sheng; Li, Na; Li, Donglai; Gao, Yun; Tian, Lu; Liu, Jianing; Zhang, Xuan; Hong, Jau-Shyong; Hou, Liyan; Zhao, Jie; Wang, Qingshan","year":2022,"journal":"Free radical biology & medicine, 188, 363-374","doi":"10.1016/j.freeradbiomed.2022.06.241","pmid":"35760232","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"SVHRSP reduced dopaminergic neuron loss and improved motor function in PD models.","whyItMatters":"This research highlights a potential new approach to treating Parkinson's disease by targeting neuroinflammation, which could lead to better management of the condition.","specificNumbers":"","methodology":"The study used mouse models of Parkinson's disease induced by rotenone and MPTP/p, along with primary neuron-glial cultures to assess the peptide's effects.","limitations":"The study was conducted in animal models, which may not fully replicate human responses, and the long-term effects of SVHRSP are still unknown."},{"rthcId":"RPEP-06648","title":"Sulfonium-Driven Neoantigen-Released DNA Nanodevice as a Precise Vaccine for Tumor Immunotherapy and Prevention.","authors":"Zhang, Yaping; Xu, Hongkun; Jiang, Leying; Liu, Zhaodi; Lian, Chenshan; Ding, Xiaofeng; Wan, Chuan; Liu, Na; Wang, Yuena; Yu, Zhiqiang; Zhu, Lizhi; Yin, Feng; Li, Zigang","year":2022,"journal":"ACS nano, 16(11), 19509-19522","doi":"10.1021/acsnano.2c09708","pmid":"36318615","tags":["peptide-vaccines","cancer"],"studyType":"animal-and-cell","evidenceStrength":"preliminary","keyFinding":"A DNA nanodevice carrying peptide neoantigens achieved remarkable results in mouse cancer models. In the B16-OVA melanoma model, it inhibited tumor growth by 50%. Even more impressively, when loaded with tumor-specific neoantigens for MC-38 colorectal cancer, it induced complete tumor regression in 80% of mice.\n\nThe key innovation is a sulfonium-based bio-orthogonal chemistry that enables reversible attachment and controlled release of antigen peptides from the DNA scaffold. The nanodevice was effectively internalized by antigen-presenting cells, enhanced cytokine secretion (TNF-α, IL-6, IL-12), stimulated antigen-specific CD8+ killer T cells, and significantly prevented lung metastases of melanoma when combined with CpG adjuvant.","whyItMatters":"Personalized cancer vaccines that train the immune system to attack tumors based on their unique mutations (neoantigens) are one of the most promising frontiers in oncology. But delivering peptide antigens effectively to immune cells remains a major challenge. This DNA nanodevice solves the delivery problem with programmable precision — each antigen peptide is at a defined position with calculable dosage. The 80% complete tumor regression rate is exceptional for a vaccine-alone approach and demonstrates the potential of precise peptide antigen delivery for personalized cancer immunotherapy.","specificNumbers":"50% melanoma growth inhibition (B16-OVA model) · 80% complete tumor regression (MC-38 neoantigen model) · enhanced TNF-α, IL-6, IL-12 cytokines · antigen-specific CD8+ T cell response · prevented lung metastases · stable in serum · effective antigen-presenting cell uptake","methodology":"Researchers created peptide-nucleic acid conjugates using propargyl sulfonium-based bio-orthogonal chemistry, which enables reversible peptide attachment under mildly alkaline conditions. The conjugates were folded into DNA nanodevice scaffolds. In vitro testing used RAW264.7 macrophages and bone marrow-derived dendritic cells (BMDCs) to assess internalization and immune activation. In vivo experiments used C57BL mice with B16-OVA melanoma (with OVA model antigen and CpG adjuvant) and MC-38 colorectal tumors (with tumor-specific neoantigen).","limitations":"All experiments were in mice, and mouse immune responses to cancer vaccines often don't predict human outcomes. The 80% complete regression was in a specific mouse tumor model (MC-38) that is relatively immunogenic. Human tumors are more heterogeneous and immunosuppressive. Manufacturing personalized DNA nanodevice vaccines for individual patients presents significant scale-up and cost challenges. Long-term immunity and memory responses were not assessed."},{"rthcId":"RPEP-06649","title":"Polarization of tumor-associated macrophages by TLR7/8 conjugated radiosensitive peptide hydrogel for overcoming tumor radioresistance.","authors":"Zhang, Yumin; Feng, Zujian; Liu, Jinjian; Li, Hui; Su, Qi; Zhang, Jiamin; Huang, Pingsheng; Wang, Weiwei; Liu, Jianfeng","year":2022,"journal":"Bioactive materials, 16, 359-371","doi":"10.1016/j.bioactmat.2021.12.033","pmid":"35386314","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The Smac-TLR7/8 peptide hydrogel self-assembled into nanofibers with porous structure and excellent biocompatibility. Upon gamma-ray radiation, it effectively polarized macrophages from the tumor-promoting M2 phenotype to the antitumor M1 phenotype.\n\nCombined with radiotherapy, the hydrogel increased tumor necrosis factor secretion, activated antitumor immune responses, and effectively inhibited tumor growth. The macrophage repolarization also rebuilt the immunosuppressive tumor microenvironment and created immunogenic phenotypes in solid tumors.\n\nThis enhanced PD-1 blockade efficacy by increasing tumor-infiltrating lymphocytes (TILs) and decreasing regulatory T cells (Treg) in two different immune activity tumor mouse models, demonstrating synergy between the hydrogel, radiotherapy, and immunotherapy.","whyItMatters":"Radiotherapy resistance is a major clinical problem — many tumors develop ways to survive radiation by exploiting the immune system. This approach elegantly turns that vulnerability into a strength: the same radiation that treats the tumor also activates the peptide hydrogel to reprogram the tumor's immune defenses. The added benefit of enhancing checkpoint immunotherapy response makes this a potentially powerful combination strategy for hard-to-treat cancers.","specificNumbers":"","methodology":"The researchers designed a self-assembling peptide hydrogel by conjugating a Smac mimetic peptide with a TLR7/8 agonist. They characterized its nanofibrous morphology, porosity, and biocompatibility. In vitro testing assessed macrophage polarization upon gamma-ray radiation. In vivo testing used two different tumor mouse models to evaluate tumor growth inhibition, immune cell infiltration, cytokine secretion, and combination efficacy with PD-1 checkpoint immunotherapy.","limitations":"All results are from mouse tumor models, which often respond differently than human cancers. The abstract does not provide specific tumor size reductions or survival data. The two tumor models used may not represent the full diversity of human cancers, particularly those with different immune landscapes. Manufacturing scalability, long-term stability, and safety of the peptide hydrogel in larger animals are not addressed. The precise radiation doses and timing needed to activate the hydrogel are not detailed in the abstract."},{"rthcId":"RPEP-06650","title":"Structural insights into multiplexed pharmacological actions of tirzepatide and peptide 20 at the GIP, GLP-1 or glucagon receptors.","authors":"Zhao, Fenghui; Zhou, Qingtong; Cong, Zhaotong; Hang, Kaini; Zou, Xinyu; Zhang, Chao; Chen, Yan; Dai, Antao; Liang, Anyi; Ming, Qianqian; Wang, Mu; Chen, Li-Nan; Xu, Peiyu; Chang, Rulve; Feng, Wenbo; Xia, Tian; Zhang, Yan; Wu, Beili; Yang, Dehua; Zhao, Lihua; Xu, H Eric; Wang, Ming-Wei","year":2022,"journal":"Nature communications, 13(1), 1057","doi":"10.1038/s41467-022-28683-0","pmid":"35217653","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Cryo-EM structures revealed how tirzepatide (dual GIP/GLP-1 agonist) and peptide 20 (triple GIP/GLP-1/glucagon agonist) achieve their multiplexed receptor activation. The structures showed both common and unique binding features at near-atomic resolution, explaining how a single peptide can effectively activate two or three different receptors. Key finding: retention of glucagon receptor function is required for the triple agonist to achieve advantages over GLP-1 monotherapy alone.","whyItMatters":"Tirzepatide is producing unprecedented weight loss and metabolic improvements in clinical trials, but how one peptide activates two different receptors was unclear. These structures provide the molecular blueprint for designing even better multi-targeting peptide drugs — and reveal that triple agonism (adding glucagon activity) may be the next frontier beyond tirzepatide.","specificNumbers":"5 cryo-EM structures solved · tirzepatide at GIPR + GLP-1R · peptide 20 at GIPR + GLP-1R + GCGR · near-atomic resolution","methodology":"Cryo-electron microscopy was used to determine five receptor-peptide complex structures: tirzepatide bound to GIPR and GLP-1R, and peptide 20 bound to GIPR, GLP-1R, and GCGR. Structural analysis identified key binding interactions, conformational changes, and receptor-specific contacts that explain dual and triple agonism. Comparisons were made to monoagonist semaglutide's binding mode.","limitations":"Structural biology study — structures represent snapshots of receptor-peptide complexes that may not capture the full dynamic signaling process. The clinical implications of specific structural features are inferred rather than directly demonstrated. Peptide 20 is a research compound, not yet in clinical development. Structures were determined in detergent/nanodisc conditions that differ from native cell membranes."},{"rthcId":"RPEP-06651","title":"Supramolecular Detoxification of Macromolecular Biotoxin through the Complexation by a Large-Sized Macrocycle.","authors":"Zhao, Liang; Chen, Junyi; Tian, Long; Zhang, Yahan; Chen, Longming; Du, Xinbei; Ma, Mengke; Li, Jian; Meng, Qingbin; Li, Chunju","year":2022,"journal":"Advanced healthcare materials, 11(14), e2200270","doi":"10.1002/adhm.202200270","pmid":"35543330","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The macrocycle increased survival rates in poisoned mice from 10% to 80%.","whyItMatters":"This research offers a potential new antidote for serious biotoxin exposures, which could save lives. It also expands the understanding of how large molecules can interact with and neutralize toxins.","specificNumbers":"","methodology":"The study involved synthesizing a water-soluble macrocycle and testing its ability to bind a spider venom peptide in vitro and in vivo.","limitations":"The study primarily focuses on a single type of biotoxin and its effects in mice, which may not fully translate to human applications."},{"rthcId":"RPEP-06652","title":"Germinal peptide eye drop promotes corneal epithelial and stromal defect healing in rabbit model.","authors":"Zhou, Lijia; Guan, Jieying; Wang, Li; Li, Xiaoyi; Pan, Zhiqiang","year":2022,"journal":"Seminars in ophthalmology, 37(5), 643-650","doi":"10.1080/08820538.2022.2053726","pmid":"35389769","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Germinal peptide eye drops improved healing and reduced inflammation compared to saline.","whyItMatters":"Improving corneal healing can enhance recovery from eye injuries and surgeries, potentially benefiting patients with similar conditions.","specificNumbers":"","methodology":"Eighty-five rabbits were divided into groups receiving different treatments, and corneal defects were created for assessment.","limitations":"The study was conducted in rabbits, so results may not directly apply to humans."},{"rthcId":"RPEP-06653","title":"Two types of peptides derived from the neurotoxin GsMTx4 inhibit a mechanosensitive potassium channel by modifying the mechanogate.","authors":"Zhou, Nan; Li, Hui; Xu, Jie; Shen, Zhong-Shan; Tang, Mingxi; Wang, Xiao-Hui; Su, Wan-Xin; Sokabe, Masahiro; Zhang, Zhe; Tang, Qiong-Yao","year":2022,"journal":"The Journal of biological chemistry, 298(9), 102326","doi":"10.1016/j.jbc.2022.102326","pmid":"35933015","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Researchers designed two short peptides from the spider venom toxin GsMTx4. The Type I peptide (Pept 01, 17 residues) showed comparable inhibitory efficacy against the stretch-activated big potassium channel (SAKcaC) as the full-length GsMTx4. Remarkably, the Type II peptide (Pept 02, just 10 residues) was even more potent than the parent toxin.\n\nBoth peptides lost their inhibitory effect when tested against a mechano-insensitive channel variant (STREX-del) and a non-mechanosensitive potassium channel (mouse Slo1), confirming they work specifically by modifying the mechanogate — the part of the channel that responds to physical stretching. Molecular dynamics simulations revealed both peptides share a structural motif: a hydrophobic head followed by a positively charged protrusion that likely mediates channel-lipid interactions.","whyItMatters":"Atrial fibrillation affects tens of millions of people worldwide, and current antiarrhythmic drugs are limited by poor efficacy and the risk of causing dangerous ventricular arrhythmias. GsMTx4 showed promise but was impractical due to its cost. By showing that a peptide just 10 amino acids long can outperform the original 34-residue toxin, this study removes a major barrier to developing spider-venom-derived antiarrhythmic drugs and opens the door to a fundamentally new approach to treating heart rhythm disorders.","specificNumbers":"","methodology":"The researchers synthesized two short peptide fragments derived from GsMTx4 and tested their effects on the stretch-activated big potassium channel (SAKcaC) from heart tissue using electrophysiology. They used site-directed mutagenesis to identify key amino acid residues required for peptide function. Molecular dynamics simulations were performed to model the structural features of the peptides. Selectivity was confirmed by testing against mechano-insensitive channel variants and non-mechanosensitive channels.","limitations":"All experiments were performed in vitro using channel proteins expressed in cell lines, not in intact heart tissue or living animals. The peptides' selectivity, safety, stability, and pharmacokinetics in vivo remain unknown. Molecular dynamics simulations provide structural hypotheses but require experimental validation. The study did not test whether these peptides actually suppress arrhythmias in animal models of atrial fibrillation."},{"rthcId":"RPEP-06654","title":"Sprouty1 exerts a preventive effect on the initiation of psoriasis by inhibiting innate immune antimicrobial peptide cathelicidin and immunocytes.","authors":"Zhou, Yuan; Wang, Ping; Chen, Xue-Yan; Yan, Bing-Xi; Landeck, Lilla; Wang, Zhao-Yuan; Xu, Fan; Zheng, Min; Man, Xiao-Yong","year":2022,"journal":"Cell proliferation, 55(10), e13290","doi":"10.1111/cpr.13290","pmid":"35716036","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Sprouty1 overexpression reduced cathelicidin production and inflammatory immune cells in psoriasis-like skin inflammation.","whyItMatters":"Understanding the role of Sprouty1 could lead to new treatments for psoriasis, a condition affecting millions. It highlights a potential target for therapeutic intervention.","specificNumbers":"","methodology":"The study used human skin samples, primary keratinocytes, and a transgenic mouse model to analyze gene expression and immune responses.","limitations":"The study primarily used animal models, which may not fully replicate human psoriasis. Further research is needed to confirm findings in humans."},{"rthcId":"RPEP-06655","title":"Transcytosis mechanisms of cell-penetrating peptides: Cation-independent CC12 and cationic penetratin.","authors":"Zhu, Minjiao; Liu, Haiyang; Cao, Wenjiao; Fang, Yuefei; Chen, Zheng; Qi, Xinming; Luo, Dawei; Chen, Chong","year":2022,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 28(9), e3408","doi":"10.1002/psc.3408","pmid":"35128758","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Oligomycin significantly inhibited the uptake of both CC12 and penetratin, indicating ATP dependence.","whyItMatters":"Understanding how these peptides penetrate cells can enhance drug delivery systems. This knowledge may lead to improved therapeutic strategies using CPPs.","specificNumbers":"","methodology":"The study employed flow cytometry and laser confocal fluorescence microscopy to analyze peptide uptake and co-localization with cellular structures.","limitations":"The study was conducted in vitro, and results may not directly translate to in vivo systems."},{"rthcId":"RPEP-06656","title":"HORDB a comprehensive database of peptide hormones.","authors":"Zhu, Ning; Dong, Fanyi; Shi, Guobang; Lao, Xingzhen; Zheng, Heng","year":2022,"journal":"Scientific data, 9(1), 187","doi":"10.1038/s41597-022-01287-5","pmid":"35469024","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06657","title":"Quantum confined peptide assemblies in a visual photoluminescent hydrogel platform and smartphone-assisted sample-to-answer analyzer for detecting trace pyrethroids.","authors":"Zhu, Xuecheng; Zhang, Ying; Han, Luxuan; Liu, Huilin; Sun, Baoguo","year":2022,"journal":"Biosensors & bioelectronics, 210, 114265","doi":"10.1016/j.bios.2022.114265","pmid":"35447398","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The fluorescence response of cyclo-WW+Zn(II) showed a linear relationship with LC concentrations from 5-350 μg/L and a limit of detection of 2.9 μg/L.","whyItMatters":"This research offers a new, portable method for detecting harmful pesticides, which is crucial for food safety and environmental monitoring.","specificNumbers":"","methodology":"The study involved synthesizing peptide-based quantum dots and testing their photoluminescent properties in a hydrogel for pesticide detection.","limitations":"The study primarily focuses on laboratory conditions, and real-world applicability may require further validation."},{"rthcId":"RPEP-06658","title":"Cell-penetrating peptides in protein mimicry and cancer therapeutics.","authors":"Zorko, Matjaž; Jones, Sarah; Langel, Ülo","year":2022,"journal":"Advanced drug delivery reviews, 180, 114044","doi":"10.1016/j.addr.2021.114044","pmid":"34774552","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CPPs can enhance the targeted delivery of anticancer drugs, with ongoing clinical trials.","whyItMatters":"Targeted drug delivery can improve treatment efficacy and reduce side effects in cancer therapy. CPPs could revolutionize how we approach cancer treatment.","specificNumbers":"","methodology":"This is a review study that summarizes existing research on CPPs, their mechanisms, and applications in cancer therapy.","limitations":"The review does not provide new experimental data and focuses on existing literature, which may limit the depth of insights."},{"rthcId":"RPEP-06659","title":"Universal immunotherapeutic strategy for hepatocellular carcinoma with exosome vaccines that engage adaptive and innate immune responses.","authors":"Zuo, Bingfeng; Zhang, Yang; Zhao, Kangjie; Wu, Li; Qi, Han; Yang, Rong; Gao, Xianjun; Geng, Mengyuan; Wu, Yingjie; Jing, Renwei; Zhou, Qibing; Seow, Yiqi; Yin, HaiFang","year":2022,"journal":"Journal of hematology & oncology, 15(1), 46","doi":"10.1186/s13045-022-01266-8","pmid":"35488312","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The vaccine led to significant tumor retardation and complete tumor eradication in mice with liver cancer.","whyItMatters":"This research could pave the way for more effective cancer treatments by personalizing immunotherapy, potentially improving outcomes for patients with liver cancer and other tumors.","specificNumbers":"","methodology":"The study involved using dendritic cell-derived exosomes modified with specific peptides to create a vaccine, which was tested in mice with liver cancer.","limitations":"The study was conducted in mice, which may not fully replicate human responses; further research is needed to confirm efficacy in humans."},{"rthcId":"RPEP-06660","title":"Human Defensins from Antivirals to Vaccine Adjuvants: Rediscovery of the Innate Immunity Arsenal.","authors":"Zupin, Luisa; Crovella, Sergio","year":2022,"journal":"Protein and peptide letters, 29(2), 121-124","doi":"10.2174/0929866528666211125110058","pmid":"34823454","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Human defensins are effective against SARS-CoV-2 and may enhance vaccine responses.","whyItMatters":"Understanding the role of defensins could lead to improved antiviral treatments and more effective vaccines, especially in the context of emerging viruses like SARS-CoV-2.","specificNumbers":"","methodology":"The study is a review of existing literature on human defensins and their roles in immunity and vaccine enhancement.","limitations":"The study is primarily a literature review and does not include new experimental data."},{"rthcId":"RPEP-06661","title":"Characterization of bioactive peptides derived from goatskin Tulum cheese of the Ereğli region at different stages of ripening.","authors":"Öztürk, Hale İnci; Oraç, Aysun; Akın, Nihat","year":2022,"journal":"Food research international (Ottawa, Ont.), 162(Pt B), 112124","doi":"10.1016/j.foodres.2022.112124","pmid":"36461355","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The number of bioactive peptides increased during ripening, with 15 different health benefits identified.","whyItMatters":"Understanding the peptide dynamics in cheese can lead to the development of functional foods that promote health. This research highlights the potential of Tulum cheese as a source of bioactive compounds.","specificNumbers":"","methodology":"Peptide profiles were analyzed using LC-MS/MS and SDS-PAGE to observe changes over 180 days.","limitations":"The study focused only on goat skin Tulum cheese and may not represent other cheese types or animal sources."},{"rthcId":"RPEP-06662","title":"Molecular insights into the mechanism of sugar-modified enkephalin binding to opioid receptors.","authors":"Ślusarz, Magdalena J","year":2022,"journal":"Computational biology and chemistry, 101, 107783","doi":"10.1016/j.compbiolchem.2022.107783","pmid":"36356466","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Sugar-modified enkephalin shows stronger binding to delta receptors than original enkephalin.","whyItMatters":"Enhancing the binding of enkephalins to specific opioid receptors could lead to more effective pain relief treatments. This research may inform the development of new therapeutic options for pain management.","specificNumbers":"","methodology":"The study investigated the binding interactions of sugar-modified and unmodified enkephalin with delta and mu opioid receptors.","limitations":"The study primarily focuses on in vitro interactions, which may not fully represent in vivo conditions."},{"rthcId":"RPEP-06663","title":"Dal 2023 Acromegaly Cancer Meta","authors":"","year":2023,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06664","title":"Demanelis 2023 Telomere Length Dynamics","authors":"","year":2023,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06665","title":"Kim 2023 Systematic Review Injection Site Reactions","authors":"","year":2023,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06666","title":"Novak 2023 Aadvac1 Tau Vaccine Phase2","authors":"","year":2023,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06667","title":"Label-Free Analysis of Binding and Inhibition of SARS-Cov-19 Spike Proteins to ACE2 Receptor with ACE2-Derived Peptides by Surface Plasmon Resonance.","authors":"Abouhajar, Fatimah; Chaudhuri, Rohit; Valiulis, Santino N; Stuart, Daniel D; Malinick, Alexander S; Xue, Min; Cheng, Quan","year":2023,"journal":"ACS applied bio materials, 6(1), 182-190","doi":"10.1021/acsabm.2c00832","pmid":"36550079","tags":[],"studyType":"laboratory","evidenceStrength":"low","keyFinding":"Two peptides derived from the ACE2 receptor's α1-helix effectively blocked SARS-CoV-2 spike protein binding. The shorter peptide [30-42] (13 amino acids) achieved maximal inhibition at lower concentrations than the longer peptide [22-44] (23 amino acids), demonstrating that shorter, well-designed peptides can be more potent viral blockers.\n\nMolecular docking models confirmed the experimental findings and identified critical amino acid residues responsible for the inhibitory effect. Both peptides blocked the spike protein's receptor-binding domain residues known to interact with ACE2.","whyItMatters":"This study demonstrates a peptide-based strategy for blocking viral entry that could serve as a template for antiviral therapeutics. The counterintuitive finding that shorter peptides can be more effective challenges assumptions about peptide drug design and provides a rapid screening methodology (SPR) that could be applied to future pandemic threats.","specificNumbers":"2 peptides tested: [30-42] (13 aa) and [22-44] (23 aa) · Shorter peptide more potent · Both blocked ACE2/RBD interaction · SPR + molecular docking validation","methodology":"In vitro study using surface plasmon resonance (SPR) competitive assays to measure how ACE2-derived peptides inhibit SARS-CoV-2 spike protein binding to the ACE2 receptor. Two peptides of different lengths based on the ACE2 peptidase domain α1-helix were tested. Results were validated with molecular docking simulations to identify critical binding residues.","limitations":"Entirely in vitro — peptide inhibition of protein-protein interactions on a sensor surface may not translate to blocking viral entry in living cells or organisms. Peptide stability, cell penetration, and bioavailability in vivo were not assessed. COVID-19 variant evolution may affect spike protein binding characteristics."},{"rthcId":"RPEP-06668","title":"Advances in CGRP Monoclonal Antibodies as Migraine Therapy: A Narrative Review.","authors":"Aditya, Suruchi; Rattan, Aditya","year":2023,"journal":"Saudi journal of medicine & medical sciences, 11(1), 11-18","doi":"10.4103/sjmms.sjmms_95_22","pmid":"36909005","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CGRP mAbs decrease headache days and improve disability in migraine patients.","whyItMatters":"CGRP mAbs represent a significant advancement in migraine treatment, addressing the need for more effective and safer options. This could lead to better management of a condition that affects many individuals.","specificNumbers":"","methodology":"The article is a narrative review summarizing recent advances in CGRP monoclonal antibody therapy for migraines.","limitations":"The review does not provide new experimental data and relies on existing studies, which may vary in quality and scope."},{"rthcId":"RPEP-06669","title":"Drastic decline in vasoactive intestinal peptide expression in the suprachiasmatic nucleus in obese mice on a long-term high-fat diet.","authors":"Afonso-Oramas, Domingo; Santana-Cordón, Laura; Lemus-Mesa, Alejandro; Teixidó-Trujillo, Silvia; Rodríguez-Rodríguez, Ana Elena; Cruz-Muros, Ignacio; González-Gómez, Miriam; Barroso-Chinea, Pedro","year":2023,"journal":"Brain research bulletin, 202, 110756","doi":"10.1016/j.brainresbull.2023.110756","pmid":"37678442","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Mice on a high-fat diet showed a significant reduction in VIP expression in the SCN.","whyItMatters":"Understanding how obesity affects neuropeptide levels can reveal mechanisms behind appetite control and energy balance, potentially leading to new obesity treatments.","specificNumbers":"","methodology":"The study used immunohistochemistry and double immunofluorescence techniques to analyze VIP levels in the SCN and nucleus accumbens of C57BL/6 mice over 365 days.","limitations":"The study was limited to female mice, and results may not directly translate to humans or other populations."},{"rthcId":"RPEP-06670","title":"Alanine-based spacers promote an efficient antigen processing and presentation in neoantigen polypeptide vaccines.","authors":"Aguilar-Gurrieri, Carmen; Barajas, Ana; Rovirosa, Carla; Ortiz, Raquel; Urrea, Victor; de la Iglesia, Nuria; Clotet, Bonaventura; Blanco, Julià; Carrillo, Jorge","year":2023,"journal":"Cancer immunology, immunotherapy : CII, 72(7), 2113-2125","doi":"10.1007/s00262-023-03409-3","pmid":"36820900","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Using an in vitro MHC-I antigen presentation assay with the SIINFEKL peptide (H-2 Kb-restricted OVA epitope), the study found:\n\n- Spacer type had the largest impact on neoantigen processing and MHC-I presentation efficiency\n- Alanine-based linkers promoted more efficient peptide presentation than the commonly used GGGS linker\n- Peptide position within the concatenated chain had minimal impact on presentation\n- Flanking regions had minimal impact on presentation\n\nThese findings suggest that spacer selection — often treated as an afterthought in vaccine design — is actually a critical determinant of vaccine immunogenicity.","whyItMatters":"Personalized cancer vaccines are one of the most promising frontiers in oncology, but their effectiveness depends on how well the immune system can process the vaccine's peptide components. This seemingly simple finding — that alanine spacers work better than standard linkers — could immediately improve the design of cancer vaccines already in clinical development.","specificNumbers":"","methodology":"In vitro assay evaluating MHC-I-dependent antigen presentation of SIINFEKL (a well-characterized model epitope). Various linker sequences were tested between concatenated neoantigen peptides. The impact of spacer type, peptide position, and flanking regions on presentation efficiency was systematically evaluated.","limitations":"The study used an in vitro assay with a single model epitope (SIINFEKL), which may not represent all neoantigen peptides. Results need validation with diverse tumor neoantigens and in vivo immune responses. The study assessed MHC-I presentation but not the resulting T cell responses. Clinical relevance in actual cancer patients remains to be demonstrated."},{"rthcId":"RPEP-06671","title":"Angiotensin-Converting Enzyme and Hypertension: A Systemic Analysis of Various ACE Inhibitors, Their Side Effects, and Bioactive Peptides as a Putative Therapy for Hypertension.","authors":"Ahmad, Hafiz; Khan, Huma; Haque, Shabirul; Ahmad, Shameem; Srivastava, Namita; Khan, Azhar","year":2023,"journal":"Journal of the renin-angiotensin-aldosterone system : JRAAS, 2023, 7890188","doi":"10.1155/2023/7890188","pmid":"37389408","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"ACE inhibitors are commonly used for hypertension, but alternative therapies like bioactive peptides are needed.","whyItMatters":"Hypertension is a significant health risk, and understanding ACE's role can lead to better treatments. Exploring new therapies could improve patient outcomes.","specificNumbers":"","methodology":"This is a systematic review analyzing various ACE inhibitors, their side effects, and potential new treatments.","limitations":"The study is a review and does not provide new experimental data; findings may not be directly applicable to all patient populations."},{"rthcId":"RPEP-06672","title":"Innovative Diagnostic Peptide-Based Technologies for Cancer Diagnosis: Focus on EGFR-Targeting Peptides.","authors":"Ahmadi, Mohammad; Ahmadyousefi, Yaghoub; Salimi, Zahra; Mirzaei, Rasoul; Najafi, Rezvan; Amirheidari, Bagher; Rahbarizadeh, Fatemeh; Kheshti, Javad; Safari, Armin; Soleimani, Meysam","year":2023,"journal":"ChemMedChem, 18(3), e202200506","doi":"10.1002/cmdc.202200506","pmid":"36357328","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Peptides targeting EGFR enhance diagnostic sensitivity for various cancers.","whyItMatters":"Improving cancer diagnosis can lead to earlier detection and better treatment outcomes. Targeting EGFR with peptides may provide a more effective approach than traditional methods.","specificNumbers":"","methodology":"The study is a review summarizing various peptide-based diagnostic technologies and their applications.","limitations":"As a review, it does not present new experimental data but summarizes existing studies, which may vary in quality."},{"rthcId":"RPEP-06673","title":"The effects of exenatide and insulin glargine treatments on bone turnover markers and bone mineral density in postmenopausal patients with type 2 diabetes mellitus.","authors":"Akyay, Ozlem Zeynep; Canturk, Zeynep; Selek, Alev; Cetinarslan, Berrin; Tarkun, İlhan; Cakmak, Yagmur; Baydemir, Canan","year":2023,"journal":"Medicine, 102(39), e35394","doi":"10.1097/MD.0000000000035394","pmid":"37773814","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Exenatide treatment resulted in decreased RANK and RANKL levels and increased OPG levels, while insulin glargine showed no significant changes.","whyItMatters":"Understanding how diabetes treatments affect bone health is crucial, especially for postmenopausal women at higher risk for fractures. Exenatide may offer benefits in bone turnover without compromising bone density.","specificNumbers":"","methodology":"Thirty postmenopausal women with type 2 diabetes were randomized to receive either exenatide or insulin glargine for 24 weeks, with bone health assessed through various markers and dual-energy X-ray absorptiometry.","limitations":"The small sample size and short duration limit the generalizability of the findings."},{"rthcId":"RPEP-06674","title":"Tirzepatide: A New Generation Therapeutic for Diabetes Type 2.","authors":"Al-Horani, Rami A; Chedid, Milad","year":2023,"journal":"Endocrine, metabolic & immune disorders drug targets, 23(8), 1046-1050","doi":"10.2174/1871530322666221004151212","pmid":"36200219","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tirzepatide improves glycemic control in type 2 diabetes patients.","whyItMatters":"Tirzepatide offers a new approach to managing type 2 diabetes, potentially improving patient outcomes. Its dual action on GLP-1 and GIP receptors may enhance glycemic control more effectively than existing treatments.","specificNumbers":"","methodology":"This is a mini-review discussing the pharmacokinetic and pharmacodynamic properties of Tirzepatide.","limitations":"As a mini-review, it does not present original research data or clinical trial results."},{"rthcId":"RPEP-06675","title":"Expression of substance P, neurokinin 1 receptor, Ki-67 and pyruvate kinase M2 in hormone receptor negative breast cancer and evaluation of impact on overall survival.","authors":"Al-Keilani, Maha S; Bdeir, Roba; Elstaty, Rana I; Alqudah, Mohammad A","year":2023,"journal":"BMC cancer, 23(1), 158","doi":"10.1186/s12885-023-10633-8","pmid":"36797689","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"High substance P levels negatively impacted overall survival in HR-ve tumors with low NK1R (p=0.021) and low Ki-67 (p=0.005).","whyItMatters":"Understanding the role of these proteins could help identify patients at higher risk and guide treatment decisions in hormone receptor negative breast cancer.","specificNumbers":"","methodology":"The study used immunohistochemical analysis to measure protein expression in 144 breast cancer tissue samples.","limitations":"The study is limited by its retrospective nature and the reliance on tissue samples, which may not fully represent the tumor microenvironment."},{"rthcId":"RPEP-06676","title":"Machine learning and molecular simulation ascertain antimicrobial peptide against Klebsiella pneumoniae from public database.","authors":"Al-Khdhairawi, Ahmad; Sanuri, Danish; Akbar, Rahmad; Lam, Su Datt; Sugumar, Shobana; Ibrahim, Nazlina; Chieng, Sylvia; Sairi, Fareed","year":2023,"journal":"Computational biology and chemistry, 102, 107800","doi":"10.1016/j.compbiolchem.2022.107800","pmid":"36516617","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06677","title":"Effects of GLP-1 Agonists on mortality and arrhythmias in patients with Type II diabetes.","authors":"Al-Sadawi, Mohammed A; Aslam, Faisal M; Tao, Michael; Alsaiqali, Mahmoud; Almasry, Ibrahim O; Fan, Roger; Rashba, Eric J; Singh, Abhijeet","year":2023,"journal":"International journal of cardiology. Heart & vasculature, 47, 101218","doi":"10.1016/j.ijcha.2023.101218","pmid":"37252197","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RA are associated with a 11% lower risk of all-cause mortality and 12% lower cardiovascular mortality.","whyItMatters":"Understanding the cardiovascular effects of GLP-1 receptor agonists is crucial for diabetes management, as these medications are widely prescribed. The findings support their safety and efficacy in reducing mortality risk.","specificNumbers":"","methodology":"The study performed a systematic review and meta-analysis of randomized controlled trials assessing GLP-1 RA effects on mortality and arrhythmias.","limitations":"The study relies on existing trials, which may vary in quality and design, and the follow-up duration was inconsistent across studies."},{"rthcId":"RPEP-06678","title":"Glucagon-like peptide 1-receptor agonists and A1c: Good for the heart but less so for the eyes?","authors":"Albert, Stewart G; Wood, Emily M; Ahir, Vaishaliben","year":2023,"journal":"Diabetes & metabolic syndrome, 17(1), 102696","doi":"10.1016/j.dsx.2022.102696","pmid":"36596264","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide was associated with a higher risk of worsening diabetic retinopathy (rr = 1.73, p = 0.02).","whyItMatters":"Understanding the balance between heart benefits and potential eye risks is crucial for managing diabetes treatment. This research can guide healthcare providers in making informed decisions about GLP-1 RA use.","specificNumbers":"","methodology":"The study conducted meta-analyses and meta-regressions on data from 7 major cardiovascular outcome trials involving 56,004 patients, and a second analysis of 11 studies with 11,894 subjects focusing on semaglutide.","limitations":"The study primarily focuses on existing trials, which may not capture all patient populations or long-term effects."},{"rthcId":"RPEP-06679","title":"The Efficacy of GLP-1 Analogues on Appetite Parameters, Gastric Emptying, Food Preference and Taste Among Adults with Obesity: Systematic Review of Randomized Controlled Trials.","authors":"Aldawsari, Malikah; Almadani, Fatima A; Almuhammadi, Nujud; Algabsani, Sarah; Alamro, Yara; Aldhwayan, Madhawi","year":2023,"journal":"Diabetes, metabolic syndrome and obesity : targets and therapy, 16, 575-595","doi":"10.2147/DMSO.S387116","pmid":"36890965","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 12 randomized controlled trials involving 445 participants, GLP-1 analogs consistently demonstrated effects on multiple appetite-related parameters:\n\n- **Appetite suppression**: Most studies showed reduced hunger and increased fullness\n- **Delayed gastric emptying**: Food stayed in the stomach longer, prolonging satiety\n- **Food preference changes**: Shifts away from high-fat and high-calorie foods\n- **Taste alterations**: Changes in taste sensitivity and perception\n\nThe review found that GLP-1 drugs work through these multiple, complementary mechanisms rather than a single pathway — helping explain their superior weight loss efficacy compared to earlier anti-obesity medications that typically targeted only one mechanism.","whyItMatters":"Understanding how GLP-1 drugs change eating behavior goes beyond academic interest — it has practical implications for patient counseling and treatment optimization. Knowing that these drugs alter food preferences and taste can help doctors prepare patients for what to expect. It also explains why patients on GLP-1 drugs often report that their relationship with food fundamentally changes, not just that they eat less. This multi-mechanism approach may be key to the long-term weight management success of these drugs.","specificNumbers":"","methodology":"The researchers conducted a systematic literature search across PubMed, Scopus, and ScienceDirect from October to December 2021. Only randomized controlled trials were included. Studies had to test GLP-1 analogs of any dosage and duration in adults with obesity without other chronic diseases, measuring appetite, gastric emptying, food preferences, or taste as outcomes. Risk of bias was assessed using the Cochrane RoB2 tool. Twelve studies met the inclusion criteria.","limitations":"The review included only 12 studies with a combined 445 participants — a relatively small evidence base. The literature search ended in December 2021, missing more recent studies including large semaglutide and tirzepatide trials. Studies varied in which GLP-1 analog was used, dosage, and duration, making direct comparisons difficult. Longer-term studies are needed to determine whether these appetite and taste effects persist over time or if tolerance develops."},{"rthcId":"RPEP-06680","title":"Euglycemic diabetic ketoacidosis after the initiation of dulaglutide in patient with type 2 diabetes.","authors":"Alduraibi, Rabia Khalid; Alrebdi, Yazeed Mohammed; Altowayan, Yosef Fahad","year":2023,"journal":"Medicine, 102(23), e34027","doi":"10.1097/MD.0000000000034027","pmid":"37335652","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The patient developed EDKA three days after starting dulaglutide.","whyItMatters":"Understanding EDKA and its triggers is crucial for effective diabetes management. This case emphasizes the need for careful monitoring when prescribing GLP1 receptor agonists.","specificNumbers":"","methodology":"This is a case report detailing the clinical presentation and management of EDKA in a patient after initiating dulaglutide.","limitations":"As a single case report, findings may not be generalizable to all patients with type 2 diabetes."},{"rthcId":"RPEP-06681","title":"Efficacy and safety of monoclonal antibodies targeting CGRP in migraine prevention. GRADE tables elaborated by the ad hoc working group of the International Headache Society.","authors":"Aleksovska, Katina; Hershey, Andrew D; Deen, Marie; Icco, Robert de; Lee, Mi Ji; Diener, Hans-Christoph","year":2023,"journal":"Cephalalgia : an international journal of headache, 43(10), 3331024231206162","doi":"10.1177/03331024231206162","pmid":"37879637","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"All four anti-CGRP monoclonal antibodies (eptinezumab, erenumab, fremanezumab, and galcanezumab) are superior to placebo for reducing monthly migraine days in both episodic and chronic migraine patients. The pooled analysis of randomized controlled trials showed consistent efficacy across all four treatments, with no major differences between them.\n\nThe evidence was assessed using the rigorous GRADE methodology and compiled into standardized evidence tables. These tables evaluate both the efficacy (reduction in migraine days) and safety profile of each antibody, providing a comprehensive evidence base for clinical guideline development.","whyItMatters":"This is not just another review — it's the International Headache Society's official evidence assessment designed to inform clinical guidelines worldwide. Having a standardized, rigorous comparison of all four anti-CGRP antibodies helps clinicians and guideline committees make evidence-based recommendations. The finding that all four are effective with no major differences gives patients and doctors flexibility in choosing based on individual factors like dosing preference and insurance coverage.","specificNumbers":"","methodology":"The researchers formulated PICO (patient/population, intervention, comparison, outcomes) questions and performed a systematic literature search for randomized controlled trials of all four anti-CGRP monoclonal antibodies. They conducted a pooled analysis using RevMan 5.4 software, using risk ratios for dichotomous outcomes and mean differences for continuous outcomes. Evidence quality was assessed using GRADE methodology, which rates certainty of evidence from very low to high. Serious adverse events were reported separately in study characteristic tables.","limitations":"The abstract does not provide specific numerical results from the pooled analysis (e.g., exact reduction in migraine days). Long-term safety outcomes beyond the duration of the included trials were not the focus. The review focused on placebo-controlled trials, so head-to-head comparisons between the antibodies were indirect rather than direct. Real-world effectiveness may differ from clinical trial efficacy."},{"rthcId":"RPEP-06682","title":"A Case Report of a Pregnant Woman With Type 2 Diabetes Mellitus Using Dulaglutide During the First Trimester of Pregnancy.","authors":"Alghamdi, Adel; Alsaeddi, Abeer; Malki, Hashem; Alsaedi, Ameerah","year":2023,"journal":"Cureus, 15(9), e44644","doi":"10.7759/cureus.44644","pmid":"37809127","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The newborn was healthy with no major malformations, but mild bilateral renal pyelectasis was noted.","whyItMatters":"Understanding the safety of diabetes medications during pregnancy is crucial for maternal and fetal health. This case adds to the limited data on dulaglutide's effects in pregnancy.","specificNumbers":"","methodology":"This is a case report detailing the clinical management of a pregnant woman with type 2 diabetes.","limitations":"This is a single case report, which limits the ability to generalize findings to a larger population."},{"rthcId":"RPEP-06683","title":"Effect of Secretion Efficiency of Mutant KRAS Neoantigen by Lactococcus lactis on the Immune Response of a Mucosal Vaccine Delivery Vehicle Targeting Colorectal Cancer.","authors":"Alias, Nur Aqlili Riana; Hoo, Winfrey Pui Yee; Siak, Pui Yan; Othman, Siti Sarah; Mohammed Alitheen, Noorjahan Banu; In, Lionel Lian Aun; Abdul Rahim, Raha; Song, Adelene Ai-Lian","year":2023,"journal":"International journal of molecular sciences, 24(10)","doi":"10.3390/ijms24108928","pmid":"37240273","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"L. lactis NZ9000 engineered with signal peptide SPK1 secreted KRAS oncopeptides (mutant 68V-DT and wild-type KRAS) more efficiently than the mutant signal peptide SPKM19, producing approximately 1.3-fold higher yields. This was unexpected, as SPKM19 had previously outperformed SPK1 with a different reporter protein.\n\nIn BALB/c mice, oral immunization with SPK1-mediated KRAS secretion produced a superior IgA immune response compared to SPKM19. However, even the SPKM19 construct triggered a positive IgA response in intestinal washes. The discrepancy between signal peptide performance with different cargo proteins was attributed to differences in size and secondary conformation of the mature proteins.","whyItMatters":"Colorectal cancer is the third most common cancer worldwide, and KRAS mutations are present in approximately 40% of cases. Current immunotherapies (checkpoint inhibitors) have limited effectiveness in most colorectal cancers. An oral vaccine that trains the gut immune system to recognize KRAS-mutant cancer cells could provide a non-invasive, targeted immunotherapy approach. Using food-grade bacteria as the delivery vehicle makes this potentially safer and more scalable than traditional vaccine platforms.","specificNumbers":"","methodology":"Two signal peptides (SPK1 and SPKM19) were used to express and secrete KRAS oncopeptides from L. lactis NZ9000. Expression and secretion efficiency were compared in vitro. BALB/c mice were orally immunized, and mucosal immune responses were assessed by measuring KRAS-specific IgA antibodies in intestinal washes.","limitations":"The study demonstrated immune response (IgA production) but did not assess whether this response actually prevents or treats colorectal tumors in an animal cancer model. IgA alone may be insufficient for anti-tumor immunity — T cell responses were not measured. The mouse immune system differs from humans. L. lactis does not colonize the gut, so repeated dosing would likely be required. The secretion yields and resulting antigen levels at the mucosal surface were not quantified in sufficient detail to predict human immunogenicity."},{"rthcId":"RPEP-06684","title":"Comparative effectiveness of glucagon-like peptide-1 receptor agonists for the management of obesity in adults without diabetes: A network meta-analysis of randomized clinical trials.","authors":"Alkhezi, Omar S; Alahmed, Abdullah A; Alfayez, Osamah M; Alzuman, Osama A; Almutairi, Abdulaali R; Almohammed, Omar A","year":2023,"journal":"Obesity reviews : an official journal of the International Association for the Study of Obesity, 24(3), e13543","doi":"10.1111/obr.13543","pmid":"36579723","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tirzepatide 10 and 15 mg resulted in more weight loss than semaglutide and liraglutide.","whyItMatters":"Understanding the effectiveness of these medications can help improve obesity management strategies. This research may guide healthcare providers in choosing the best treatment options for patients.","specificNumbers":"","methodology":"A Bayesian network meta-analysis of randomized clinical trials was conducted.","limitations":"The analysis is based on existing trials, which may have variability in study design and patient populations."},{"rthcId":"RPEP-06685","title":"Impact of anti-CGRP monoclonal antibodies on migraine attack accompanying symptoms: A real-world evidence study.","authors":"Alpuente, Alicia; Torre-Sune, Anna; Caronna, Edoardo; Gine-Cipres, Eulalia; Torres-Ferrús, Marta; Pozo-Rosich, Patricia","year":2023,"journal":"Cephalalgia : an international journal of headache, 43(8), 3331024231177636","doi":"10.1177/03331024231177636","pmid":"37555331","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Of 158 patients, 44% achieved a 50% or greater reduction in headache days at month 6. In this responder group, headache days decreased by 9.4 days/month (p<0.001). Beyond headache reduction, the ratio of days with specific symptoms decreased significantly:\n\n- Photophobia: -19.5% (p<0.001)\n- Phonophobia: -12.1% (p=0.010)\n- Aura: -25.1% (p=0.008)\n\nThese reductions exceeded the proportional decrease in headache days, meaning the symptoms improved independently, not just because there were fewer migraines. Nausea and dizziness decreased only in proportion to fewer headache days. Higher baseline photophobia ratios predicted better response between months 3-6 (IRR=0.928, p=0.040), suggesting CGRP's role in light sensitivity may identify patients likely to benefit.","whyItMatters":"Clinical trials of anti-CGRP antibodies focused almost exclusively on headache day reduction, largely ignoring the accompanying symptoms that migraine patients often describe as equally disabling. This study shows these drugs do more than just reduce headache frequency — they specifically improve sensory symptoms like light sensitivity and aura, suggesting CGRP has a direct role in these experiences. This is clinically important because patients with prominent photophobia may be particularly good candidates for anti-CGRP therapy.","specificNumbers":"","methodology":"This was a prospective real-world study at a headache clinic. 158 migraine patients treated with erenumab, galcanezumab, or fremanezumab completed daily electronic diaries tracking headache frequency and accompanying symptoms (photophobia, phonophobia, nausea, dizziness, aura). Symptom ratios were calculated relative to headache days at baseline, 3 months, and 6 months. Responders (≥50% headache reduction) were compared to non-responders.","limitations":"This was an observational real-world study without a placebo control, so some symptom improvement could reflect placebo effects or natural disease fluctuation. The sample size of 158 limits subgroup analyses. Symptom assessment relied on patient-reported eDiaries, which may have recording biases. The 6-month follow-up may not capture longer-term effects. The three different anti-CGRP antibodies were analyzed together rather than separately."},{"rthcId":"RPEP-06686","title":"Discovery of endosomalytic cell-penetrating peptides based on bacterial membrane-targeting sequences.","authors":"An, Chuanjing; Wei, Sheng; Dao, Yuankun; Wang, Xiaoya; Dong, Weidong; You, Xue; Tian, Chao; Zhang, Zhili; Dong, Suwei","year":2023,"journal":"Bioorganic chemistry, 134, 106424","doi":"10.1016/j.bioorg.2023.106424","pmid":"36868126","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Six peptides based on bacterial membrane-targeting sequences (MTSs) all showed cell-penetrating ability. Two D-peptide versions — d-EcMTS (from E. coli) and d-TpMTS (from T. pallidum) — demonstrated the additional critical ability to escape from endosomes after cellular uptake and localize at the endoplasmic reticulum (ER).\n\nThe utility was validated by successful intracellular delivery of green fluorescent protein (GFP), a large biomacromolecule that cannot enter cells on its own. The D-amino acid configuration provides protease resistance, addressing the stability limitation of natural L-peptide CPPs. The results suggest that the vast pool of bacterial MTSs represents an untapped resource for developing novel endosome-escaping cell-penetrating peptides.","whyItMatters":"Endosomal entrapment is the single biggest bottleneck in intracellular delivery of biological therapeutics — an estimated 99% of endocytosed molecules are degraded in lysosomes before they can act. Current CPPs get cargo into cells but mostly fail at endosomal escape. By mining bacterial membrane-targeting sequences — peptides that evolved to interact with and disrupt cellular membranes — this study identifies a new source of peptide delivery vehicles that naturally possess endosome-disrupting activity, potentially solving the efficiency problem that has limited biologics delivery for decades.","specificNumbers":"","methodology":"Six peptides based on bacterial membrane-targeting sequences were synthesized in both L- and D-amino acid configurations. Cell penetration was assessed using fluorescence microscopy and flow cytometry. Endosomal escape was evaluated by subcellular co-localization studies with endosomal and ER markers. Functional utility was demonstrated by intracellular delivery of GFP as a model cargo protein.","limitations":"The study is entirely in vitro using cultured cells — in vivo delivery, biodistribution, and potential toxicity were not assessed. Only GFP was tested as cargo, and larger or differently structured cargoes may not be equally deliverable. The endosomal escape efficiency was demonstrated qualitatively but not quantified. The mechanism by which MTSs disrupt endosomal membranes was not elucidated in detail. Potential cytotoxicity from membrane-disrupting peptides at higher concentrations was not thoroughly explored."},{"rthcId":"RPEP-06687","title":"Tirzepatide for type 2 diabetes.","authors":"Anderson, Sarah L; Marrs, Joel C","year":2023,"journal":"Drugs in context, 12","doi":"10.7573/dic.2023-6-1","pmid":"37664792","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tirzepatide led to a reduction in glycosylated hemoglobin by -1.24% to -2.11% and weight loss of up to 15.5 kg compared to placebo.","whyItMatters":"This research highlights tirzepatide as a potential breakthrough for patients with T2D who have difficulty managing their condition with existing treatments. Its dual action may provide better control over blood sugar and weight.","specificNumbers":"","methodology":"The study reviewed data from five clinical trials involving 6,278 participants, focusing on glycemic control and weight loss outcomes.","limitations":"The review primarily focuses on clinical trial data, which may not fully represent real-world effectiveness and safety."},{"rthcId":"RPEP-06688","title":"Novel enhancers of guanylyl cyclase-A activity acting via allosteric modulation.","authors":"Andresen, Henriette; Pérez-Ternero, Cristina; Robinson, Jerid; Dickey, Deborah M; Hobbs, Adrian J; Potter, Lincoln R; Levy, Finn Olav; Cataliotti, Alessandro; Moltzau, Lise Román","year":2023,"journal":"British journal of pharmacology, 180(24), 3254-3270","doi":"10.1111/bph.16203","pmid":"37522273","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"High-throughput screening and in silico design identified novel small molecule allosteric enhancers of GC-A. These compounds enhanced ANP and BNP effects in cellular systems expressing GC-A and enhanced ANP-induced vasorelaxation in rat aortic rings. The mechanism is novel — not mediated through previously known allosteric binding sites. Selectivity between GC-A and the related receptor GC-B depended on a single amino acid residue. The compounds represent a new class of tools for enhancing natriuretic peptide signaling.","whyItMatters":"Heart failure treatment has long sought a way to boost the natriuretic peptide system without injecting peptides. These small molecules could become the first oral drugs that enhance the body's own cardiac protection. By amplifying rather than replacing natriuretic peptide signaling, they work with the body's natural regulatory system — potentially avoiding the hypotension issues that limited nesiritide's clinical success.","specificNumbers":"","methodology":"High-throughput screening identified initial hits, which were optimized through in silico computational design. GC-A activation was measured via cyclic GMP production in QBIHEK293A cells expressing GC-A, GC-B, or chimeric receptors using AlphaScreen technology. Binding assays used 125I-ANP in membrane preparations and whole cells. Functional vasorelaxation was tested in isolated Wistar rat aortic rings. Receptor selectivity was mapped to individual amino acid residues using chimeric GC-A/GC-B receptors.","limitations":"All experiments were in vitro and in isolated rat tissue — no in vivo cardiovascular effects were tested. The pharmacokinetic properties (oral bioavailability, half-life, metabolism) of the compounds are unknown. The compounds enhance peptide effects rather than activating GC-A independently, meaning they depend on adequate endogenous ANP/BNP levels. Whether the vasorelaxation effect translates to blood pressure reduction in living animals is untested. The selectivity mechanism (single amino acid) may complicate drug development if species differences exist."},{"rthcId":"RPEP-06689","title":"Transportan 10 Induces Perturbation and Pores Formation in Giant Plasma Membrane Vesicles Derived from Cancer Liver Cells.","authors":"Anselmo, Sara; Sancataldo, Giuseppe; Baiamonte, Concetta; Pizzolanti, Giuseppe; Vetri, Valeria","year":2023,"journal":"Biomolecules, 13(3)","doi":"10.3390/biom13030492","pmid":"36979427","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Using fluorescence lifetime imaging microscopy (FLIM) with phasor analysis, researchers visualized TP10's behavior on cancer cell-derived membrane vesicles in real time. They identified concentration-dependent mechanisms: at lower concentrations, TP10 translocated across membranes and accumulated in the vesicle lumen (internalization). At higher concentrations, it induced membrane perturbation, pore formation, and ultimately membrane collapse and disruption. The FLIM-phasor approach enabled monitoring of these spatially heterogeneous, highly dynamic events as they occurred.","whyItMatters":"Cell-penetrating peptides are being developed for both drug delivery and direct anticancer activity, but the mechanisms by which they interact with cell membranes are poorly understood. This study provides the first real-time visualization of how concentration determines whether a CPP acts as a quiet delivery vehicle or a membrane-destroying weapon. This knowledge is essential for safely designing peptide-based therapeutics — using the right concentration for delivery without causing unwanted cell death, or deliberately using higher concentrations for anticancer effects.","specificNumbers":"","methodology":"Researchers generated giant plasma membrane vesicles (GPMVs) from cancer liver cells to study membrane interactions in a controlled system. They used fluorescence lifetime imaging microscopy (FLIM) coupled with phasor approach analysis to track TP10's behavior at the membrane in real time. Different peptide concentrations were tested to map the transition from translocation to membrane disruption.","limitations":"The study used giant plasma membrane vesicles (GPMVs) derived from cancer cells, which are simplified models lacking the full complexity of living cells (no cytoskeleton, intracellular organelles, or active repair mechanisms). Results may not translate directly to intact cells or in vivo conditions. Only cancer liver cells were used as the membrane source, so the findings may not apply to all cell types. No drug cargo delivery was tested."},{"rthcId":"RPEP-06690","title":"SGLT2i and GLP-1 RA therapy in type 1 diabetes and reno-vascular outcomes: a real-world study.","authors":"Anson, Matthew; Zhao, Sizheng S; Austin, Philip; Ibarburu, Gema H; Malik, Rayaz A; Alam, Uazman","year":2023,"journal":"Diabetologia, 66(10), 1869-1881","doi":"10.1007/s00125-023-05975-8","pmid":"37505282","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 196,691 type 1 diabetes patients, 1,822 were treated with GLP-1 RAs and 992 with SGLT2 inhibitors for at least 6 months. Both lowered HbA1c: SGLT2i reduced it by 2.6 mmol/mol (0.2%) and GLP-1 RA by 5.4 mmol/mol (0.5%).\n\nOver 5 years, SGLT2i users showed kidney function preservation (eGFR +3.5 ml/min/1.73m²) while GLP-1 RA users showed decline (eGFR -7.2 ml/min/1.73m²). SGLT2i users had significantly lower risks of heart failure (RR 0.44, p=0.009), chronic kidney disease (RR 0.49, p=0.012), and all-cause hospitalization (RR 0.59, p<0.0001). However, SGLT2i users had higher rates of diabetic ketoacidosis (RR 2.08, p=0.031) and urinary tract infections (RR 2.27, p=0.019).","whyItMatters":"Type 1 diabetes patients face high rates of kidney disease and heart failure over their lifetimes, and insulin alone doesn't fully protect against these complications. This is the largest real-world study comparing GLP-1 RAs and SGLT2 inhibitors in type 1 diabetes, providing crucial evidence for an off-label use that many clinicians are already prescribing. The stark difference in kidney outcomes could influence treatment decisions for thousands of patients.","specificNumbers":"","methodology":"This was a retrospective cohort study using the TriNetX platform, a global network of anonymized real-time medical records. Researchers identified all adults with type 1 diabetes who had been treated with either SGLT2 inhibitors or GLP-1 RAs for at least 6 months alongside insulin. They analyzed HbA1c changes, kidney function (eGFR), adverse events, and cardio-renal outcomes over a 5-year follow-up period.","limitations":"This is a retrospective observational study, so it cannot prove causation. The TriNetX platform may have coding inaccuracies, and some patients may have been misclassified between type 1 and type 2 diabetes. The SGLT2i group was smaller (992 vs 1,822) and there may be selection bias in which patients received each drug. Propensity score matching details were not described in the abstract. The higher DKA risk with SGLT2i is a known class effect that may be manageable with proper patient education."},{"rthcId":"RPEP-06691","title":"Cell-Surface-Retained Peptide Additives for the Cytosolic Delivery of Functional Proteins.","authors":"Arafiles, Jan Vincent V; Franke, Jonathan; Franz, Luise; Gómez-González, Jacobo; Kemnitz-Hassanin, Kristin; Hackenberger, Christian P R","year":2023,"journal":"Journal of the American Chemical Society, 145(45), 24535-48","doi":"10.1021/jacs.3c05365","pmid":"37906525","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The hydrophobic CPP-additive improved protein uptake and was effective at low micromolar concentrations.","whyItMatters":"Improving protein delivery mechanisms can enhance therapeutic applications in medicine and biotechnology. This research provides a promising strategy for intracellular delivery of proteins.","specificNumbers":"","methodology":"The study involved designing CPP-additives, conducting cell viability tests, and using fluorescence microscopy to evaluate protein uptake.","limitations":"The study primarily focuses on in vitro experiments, and further research is needed to confirm efficacy in vivo."},{"rthcId":"RPEP-06692","title":"Semaglutide reduces alcohol intake and relapse-like drinking in male and female rats.","authors":"Aranäs, Cajsa; Edvardsson, Christian E; Shevchouk, Olesya T; Zhang, Qian; Witley, Sarah; Blid Sköldheden, Sebastian; Zentveld, Lindsay; Vallöf, Daniel; Tufvesson-Alm, Maximilian; Jerlhag, Elisabet","year":2023,"journal":"EBioMedicine, 93, 104642","doi":"10.1016/j.ebiom.2023.104642","pmid":"37295046","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide reduced alcohol intake and relapse-like drinking in both male and female rats.","whyItMatters":"Understanding how semaglutide affects alcohol consumption could lead to new treatments for alcohol use disorder, especially in overweight patients.","specificNumbers":"","methodology":"The study used an intermittent access model to assess alcohol intake and relapse behaviors, alongside imaging techniques to observe semaglutide binding in the brain.","limitations":"The study was conducted in rodents, and results may not directly translate to humans."},{"rthcId":"RPEP-06693","title":"A Comparison of Cathelicidin Levels in the Skin of Leprosy Patients and Their Household Contacts.","authors":"Argentina, Fifa; Suwarsa, Oki; Gunawan, Hendra; Berbudi, Afiat","year":2023,"journal":"Acta medica academica, 52(3), 195-200","doi":"10.5644/ama2006-124.424","pmid":"38407086","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Cathelicidin levels differed significantly across all three groups (P<0.050):\n- Leprosy patients: 256.8 ± 22.9 pg/ml\n- Household contacts: 25.9 ± 2.7 pg/ml\n- Healthy controls: 1.4 ± 0.1 pg/ml\n\nThe approximately 10-fold difference between patients and contacts, and the nearly 200-fold difference between patients and healthy controls, demonstrates a dose-response relationship between cathelicidin production and the degree of exposure to or infection with Mycobacterium leprae. Notably, even asymptomatic household contacts had significantly elevated cathelicidin compared to unexposed healthy individuals.","whyItMatters":"Cathelicidin is one of the body's key natural antimicrobial peptides. Understanding how its levels change during leprosy infection could reveal how the immune system fights this disease, potentially leading to new biomarkers for exposure risk assessment or new therapeutic approaches that boost the body's natural peptide-based defenses.","specificNumbers":"","methodology":"This was an analytic observational study with a cross-sectional design. Fifty-four subjects participated across three groups: leprosy patients, household contacts, and healthy controls. Cathelicidin levels in skin samples were measured using the ELISA (enzyme-linked immunosorbent assay) method. Statistical analysis including univariate and bivariate analysis was performed using SPSS software.","limitations":"The cross-sectional design cannot determine whether elevated cathelicidin causes immune protection or is simply a response to infection. The sample size of 54 subjects is relatively small. The study did not differentiate between leprosy subtypes (paucibacillary vs. multibacillary), which may have different immune profiles. Geographic and genetic factors in the study population may limit generalizability."},{"rthcId":"RPEP-06694","title":"Gene Expression of Human Beta-Defensin-3 and Cathelicidin in the Skin of Leprosy Patients, Household Contacts, and Healthy Individuals from Indonesia.","authors":"Argentina, Fifa; Suwarsa, Oki; Gunawan, Hendra; Berbudi, Afiat","year":2023,"journal":"Clinical, cosmetic and investigational dermatology, 16, 1485-1492","doi":"10.2147/CCID.S405932","pmid":"37333516","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"HBD-3 gene expression in leprosy skin lesions had a median value of 260.61 compared to 1.00 in healthy skin (p < 0.0001) — a roughly 260-fold increase. Cathelicidin expression in lesions was 38.72 versus 1.00 in healthy skin (p < 0.0001).\n\nCritically, household contacts who did not have leprosy also showed elevated antimicrobial peptide levels: HBD-3 at 7.93 and cathelicidin at 9.8, both substantially higher than healthy individuals. Normal (non-lesional) skin in leprosy patients showed intermediate levels (HBD-3: 1.91; cathelicidin: 0.48). These findings suggest a gradient of antimicrobial peptide response from healthy individuals through exposed contacts to active disease, potentially reflecting both infection response and protective immunity.","whyItMatters":"Leprosy still affects over 200,000 new patients annually worldwide, and understanding the skin's natural immune defense against the bacterium is crucial for developing better prevention and treatment strategies. The finding that household contacts have elevated antimicrobial peptides suggests these molecules may provide some natural protection against developing the disease, even after exposure.","specificNumbers":"","methodology":"This was an analytic observational study conducted at Dr Mohammad Hoesin General Hospital in Palembang, Indonesia from January 2021 to June 2022. Researchers collected 72 skin samples from four groups of 18 subjects each: leprosy lesional skin, leprosy non-lesional skin, household contact skin, and healthy individual skin. Gene expression of HBD-3 and cathelicidin was measured and compared across groups using Kruskal-Wallis and Mann-Whitney statistical tests.","limitations":"The study had a relatively small sample size of 18 subjects per group, limiting generalizability. It was conducted at a single hospital in Indonesia. Gene expression was measured at a single time point, so it's unclear how antimicrobial peptide levels change over the course of disease. The study measured mRNA expression rather than peptide protein levels, which don't always correlate. The household contacts' elevated levels could reflect subclinical infection rather than protective immunity."},{"rthcId":"RPEP-06695","title":"GLP-1 Receptor Agonists and Related Mental Health Issues; Insights from a Range of Social Media Platforms Using a Mixed-Methods Approach.","authors":"Arillotta, Davide; Floresta, Giuseppe; Guirguis, Amira; Corkery, John Martin; Catalani, Valeria; Martinotti, Giovanni; Sensi, Stefano L; Schifano, Fabrizio","year":2023,"journal":"Brain sciences, 13(11)","doi":"10.3390/brainsci13111503","pmid":"38002464","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Out of 43,710 total comments, 620 mentioned insomnia, 353 anxiety, and 204 depression related to GLP-1 RAs.","whyItMatters":"Understanding the mental health implications of GLP-1 receptor agonists is crucial as their popularity rises. This research sheds light on potential risks and benefits that need to be addressed.","specificNumbers":"","methodology":"A mixed-methods approach was used, analyzing comments from social media platforms like Reddit, YouTube, and TikTok.","limitations":"The study relies on social media data, which may not represent the broader population's views and lacks clinical validation."},{"rthcId":"RPEP-06696","title":"Use of optimal medical therapy in patients with diabetes and atherosclerotic cardiovascular disease: Insights from a prospective longitudinal cohort study.","authors":"Arnold, Suzanne V; de Lemos, James A; Zheng, Luke; Rosenson, Robert S; Ballantyne, Christie M; Alam, Shushama; Bhatt, Deepak L; Cannon, Christopher P; Kosiborod, Mikhail","year":2023,"journal":"Diabetes, obesity & metabolism, 25(6), 1750-1757","doi":"10.1111/dom.15032","pmid":"36843558","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Only 11% of patients received comprehensive optimal medical therapy, an increase from 8% at baseline.","whyItMatters":"This research underscores the ongoing challenges in treating diabetic patients with heart disease, pointing to significant gaps in care that could lead to worse health outcomes.","specificNumbers":"","methodology":"The study followed 1,590 patients with atherosclerotic cardiovascular disease and diabetes over two years, assessing their use of optimal medical therapy.","limitations":"The study is limited to a specific patient population and may not represent all diabetic patients with cardiovascular disease."},{"rthcId":"RPEP-06697","title":"Efficacy and safety of once-weekly efpeglenatide in people with suboptimally controlled type 2 diabetes: The AMPLITUDE-D, AMPLITUDE-L and AMPLITUDE-S randomized controlled trials.","authors":"Aroda, Vanita R; Frias, Juan Pablo; Ji, Linong; Niemoeller, Elisabeth; Nguyên-Pascal, My-Liên; Denkel, Karl; Espinasse, Melanie; Guo, Hailing; Baek, SeungJae; Choi, JaeDuk; Lingvay, Ildiko","year":2023,"journal":"Diabetes, obesity & metabolism, 25(8), 2084-2095","doi":"10.1111/dom.15079","pmid":"37013892","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Efpeglenatide was non-inferior to dulaglutide in reducing HbA1c levels, with a treatment difference of -0.03% to -0.08%.","whyItMatters":"This research provides insights into new treatment options for managing type 2 diabetes, which is crucial for improving patient outcomes. Understanding the safety and efficacy of efpeglenatide can help healthcare providers make informed treatment decisions.","specificNumbers":"","methodology":"Three phase 3 randomized controlled trials compared efpeglenatide with dulaglutide and placebo in patients with type 2 diabetes.","limitations":"The trials were terminated early due to funding issues, limiting the data on long-term efficacy and safety."},{"rthcId":"RPEP-06698","title":"Safety and tolerability of semaglutide across the SUSTAIN and PIONEER phase IIIa clinical trial programmes.","authors":"Aroda, Vanita R; Erhan, Umut; Jelnes, Peter; Meier, Juris J; Abildlund, Morten Tind; Pratley, Richard; Vilsbøll, Tina; Husain, Mansoor","year":2023,"journal":"Diabetes, obesity & metabolism, 25(5), 1385-1397","doi":"10.1111/dom.14990","pmid":"36700417","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 16 Phase IIIa trials (n=11,159; subcutaneous semaglutide n=3,150; oral semaglutide n=4,116):\n\n- GI disorders: 41.9% (subcutaneous) / 39.1% (oral) vs 22.0% / 24.8% comparators — most common during dose escalation, decreasing with continued therapy\n- No increased risk vs comparators for: kidney disorders, acute pancreatitis, malignant neoplasms, hypoglycemia, heart failure, or other cardiovascular events\n- Cholelithiasis (gallstones): incidence higher with both formulations vs placebo\n- Diabetic retinopathy: higher with subcutaneous semaglutide vs placebo in SUSTAIN 6\n- Small pulse rate increases with both formulations; no increased arrhythmias\n- Fatal adverse events: similar rates between semaglutide and comparators\n- CVOTs: reduced MACE with subcutaneous semaglutide; non-inferiority met with oral","whyItMatters":"As semaglutide is now prescribed to millions of people for both diabetes and obesity, this comprehensive safety analysis from the largest clinical trial programmes provides essential evidence for informed prescribing decisions. The reassuring safety profile across multiple organ systems supports its widespread use while identifying specific areas for monitoring (gallstones, retinopathy).","specificNumbers":"","methodology":"Pooled analysis of adverse event data from 16 randomized, placebo- or active-controlled Phase IIIa trials from the SUSTAIN programme (subcutaneous semaglutide) and PIONEER programme (oral semaglutide). Separate analyses were conducted for cardiovascular outcomes trials (CVOTs; n=6,480). Safety endpoints included GI disorders, kidney events, pancreatitis, neoplasms, hypoglycemia, retinopathy, cardiovascular events, and mortality.","limitations":"The analysis covers Phase IIIa trial data, which may not capture rare events or long-term safety beyond trial durations. Trial populations were selected using inclusion/exclusion criteria and may not represent all real-world patients. The higher retinopathy signal in SUSTAIN 6 may be related to rapid HbA1c improvement rather than a direct drug effect. Post-marketing surveillance has since provided additional safety data not captured here."},{"rthcId":"RPEP-06699","title":"Oral Absorption of Middle-to-Large Molecules and Its Improvement, with a Focus on New Modality Drugs.","authors":"Asano, Daigo; Takakusa, Hideo; Nakai, Daisuke","year":2023,"journal":"Pharmaceutics, 16(1)","doi":"10.3390/pharmaceutics16010047","pmid":"38258058","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Oral bioavailability of peptides in Rybelsus and Mycapssa is around 1%.","whyItMatters":"Improving the oral absorption of larger molecules could lead to more effective and convenient treatments for various conditions. This is particularly important for patients who prefer oral medications over injections.","specificNumbers":"","methodology":"The article reviews recent advancements and technologies aimed at enhancing the oral absorption of middle-to-large molecules.","limitations":"The review primarily focuses on existing drugs and does not present new experimental data or clinical trials."},{"rthcId":"RPEP-06700","title":"Teleost Piscidins-In Silico Perspective of Natural Peptide Antibiotics from Marine Sources.","authors":"Asensio-Calavia, Patricia; González-Acosta, Sergio; Otazo-Pérez, Andrea; López, Manuel R; Morales-delaNuez, Antonio; Pérez de la Lastra, José Manuel","year":2023,"journal":"Antibiotics (Basel, Switzerland), 12(5)","doi":"10.3390/antibiotics12050855","pmid":"37237758","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Bioinformatics analysis of all reviewed piscidin sequences in the UniProt database revealed that these fish-exclusive antimicrobial peptides share amphipathic alpha-helical structures with positively charged residues that drive their antibacterial activity. Piscidins are effective against both Gram-positive and Gram-negative bacteria that cause disease in fish and humans.\n\nA key advantage is their stability in high-salt and metal-rich environments — conditions that disable many other antimicrobial peptides. The study identified potential applications beyond antibiotics, including anti-cancer and anti-inflammatory uses, and suggests piscidins could inspire treatments for multidrug-resistant bacterial infections.","whyItMatters":"With antibiotic resistance rising globally, scientists are searching nature for new antimicrobial compounds. Piscidins represent a unique class of antimicrobial peptides found only in bony fish, shaped by millions of years of evolution in microbe-rich aquatic environments. Their stability in salt water — where most other AMPs lose function — makes them particularly interesting for development as therapeutic agents, since salt tolerance has been a major limitation of other antimicrobial peptides in clinical settings.","specificNumbers":"Exclusive to Teleost fish · Effective against Gram-positive and Gram-negative bacteria · Amphipathic alpha-helical structure · Stable in high-salt environments · Broader spectrum than conventional antibiotics","methodology":"Comprehensive bioinformatics analysis of all piscidin sequences in the 'reviewed' category of the UniProt protein database. The authors used computational tools to analyze structural properties, amphipathic architecture, charge distribution, and predicted biological activities. The study also synthesized published experimental data on piscidin bioactivity.","limitations":"This is primarily a computational (in silico) and literature review study. Bioinformatics predictions of antimicrobial activity need experimental validation. The study does not present new laboratory or clinical data on piscidin efficacy. Translation from fish immune peptides to human therapeutics would require extensive pharmacological development including toxicity testing, stability optimization, and delivery system development."},{"rthcId":"RPEP-06701","title":"Hybrid peptides as platform for synchronized combination therapy.","authors":"Ashrafichoobdar, Elahe; Perez, Tanner; Ayalew, Luladey; Gorbanwand, Venus; Monroy, Joel; Slowinska, Katarzyna","year":2023,"journal":"Colloids and surfaces. B, Biointerfaces, 226, 113326","doi":"10.1016/j.colsurfb.2023.113326","pmid":"37116378","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The hybrid peptide allows for colocalized delivery of three drugs, enhancing their efficacy.","whyItMatters":"This research could lead to more effective cancer treatments by improving how multiple drugs are delivered to tumors. It also opens the door for personalized medicine approaches.","specificNumbers":"","methodology":"The study involved designing a hybrid peptide and testing its ability to deliver three cancer drugs in a coordinated manner.","limitations":"The study primarily focuses on in vitro results, which may not fully translate to in vivo effectiveness in humans."},{"rthcId":"RPEP-06702","title":"Peptide Receptor Radionuclide Therapy in Merkel Cell Carcinoma: A Comprehensive Review.","authors":"Askari, Emran; Moghadam, Soroush Zarehparvar; Wild, Damian; Delpassand, Ebrahim; Baldari, Sergio; Nilica, Bernhard; Hartrampf, Philipp E; Kong, Grace; Grana, Chiara Maria; Alexander Walter, Martin; Capoccetti, Francesca; Kasi, Pashtoon Murtaza; Strosberg, Jonathan","year":2023,"journal":"Journal of nuclear medicine technology, 51(1), 22-25","doi":"10.2967/jnmt.122.264904","pmid":"36195446","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Of 37 patients with metastatic Merkel cell carcinoma who received 1-5 cycles of PRRT using 177Lu- or 90Y-labeled somatostatin analogs (cumulative activity 1.5-30 GBq), radiographic response data was available for 19 who received PRRT alone. Six of these 19 patients (31.6%) achieved objective responses ranging from partial to complete. No severe adverse events were reported across the treated cohort.","whyItMatters":"Metastatic Merkel cell carcinoma has limited treatment options and a poor prognosis. While immunotherapy has improved outcomes, many patients don't respond or eventually progress. PRRT offers a mechanistically different approach — using peptides to deliver targeted radiation directly to tumor cells — that could fill an important treatment gap for this rare cancer.","specificNumbers":"","methodology":"The authors performed a comprehensive literature review searching for all published reports of PRRT use in metastatic Merkel cell carcinoma. They compiled data from individual case reports and small series, totaling 37 treated patients. Response was assessed radiographically in patients who received PRRT as a standalone therapy.","limitations":"The evidence quality is low — data comes from retrospective case reports and small series rather than controlled trials. The total of 37 patients is very small, and radiographic response data was only available for 19 who received PRRT alone. Publication bias likely favors positive outcomes. Patient selection (requiring somatostatin receptor expression) means results may not apply to all Merkel cell carcinoma cases."},{"rthcId":"RPEP-06703","title":"Synergistic Antimicrobial Action of Lactoferrin-Derived Peptides and Quorum Quenching Enzymes.","authors":"Aslanli, Aysel; Domnin, Maksim; Stepanov, Nikolay; Efremenko, Elena","year":2023,"journal":"International journal of molecular sciences, 24(4)","doi":"10.3390/ijms24043566","pmid":"36834977","tags":["antimicrobial-peptides"],"studyType":"basic-research","evidenceStrength":"preliminary","keyFinding":"Combining the milk-derived antimicrobial peptide lactoferricin (Lfcin) with an enzyme that disrupts bacterial communication (His6-OPH, a quorum quenching enzyme) produced synergistic antimicrobial effects against bacteria and yeasts. The enzyme-peptide combination killed microorganisms more effectively than the peptide alone. Additionally, Lfcin stabilized the enzyme's activity and increased its catalytic efficiency for breaking down bacterial signaling molecules (quorum sensing lactones).\n\nMolecular docking simulations first predicted which peptide-enzyme pairings would work best, and experimental testing confirmed that His6-OPH/Lfcin was the optimal combination among three lactoferrin-derived peptides and two enzymes tested.","whyItMatters":"Bacteria develop resistance partly through quorum sensing — a communication system that coordinates collective behaviors like biofilm formation and toxin production. By combining a peptide that kills bacteria directly with an enzyme that disrupts their communication, this dual approach attacks pathogens on two fronts simultaneously, making resistance development much harder. This 'peptide + enzyme' strategy represents a novel paradigm for fighting drug-resistant infections.","specificNumbers":"3 lactoferrin-derived peptides tested · 2 quorum quenching enzymes · His6-OPH/Lfcin selected as best combination · Improved antimicrobial activity vs Lfcin alone · Enhanced catalytic efficiency for lactone hydrolysis","methodology":"In silico molecular docking first screened combinations of three lactoferrin-derived peptides (lactoferricin, lactoferampin, Lf(1-11)) with two quorum quenching enzymes (His6-OPH and penicillin acylase). The His6-OPH/Lfcin combination was selected for experimental validation. Physical-chemical characterization assessed enzyme stability. Antimicrobial activity was tested against bacteria and yeasts using the combination versus peptide alone.","limitations":"All results are in vitro — no animal or clinical testing was performed. The specific bacterial and yeast strains tested are not detailed in the abstract. The practical delivery mechanism for an enzyme-peptide combination (stability, shelf life, formulation) is not addressed. Whether the synergy holds against drug-resistant clinical isolates and biofilms in real-world conditions remains unknown."},{"rthcId":"RPEP-06704","title":"Cell penetrating peptides: Highlighting points in cancer therapy.","authors":"Asrorov, Akmal M; Wang, Huiyuan; Zhang, Meng; Wang, Yonghui; He, Yang; Sharipov, Mirkomil; Yili, Abulimiti; Huang, Yongzhuo","year":2023,"journal":"Drug development research, 84(6), 1037-1071","doi":"10.1002/ddr.22076","pmid":"37195405","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CPP-based drug delivery systems effectively inhibited tumor volume and weight in mouse models across numerous studies. However, the review found that only rare cases demonstrated actual tumor level reduction beyond volume shrinkage, and even fewer progressed to further development stages.\n\nThe integration of chemical synthesis with CPP development has been the most successful approach, with at least one CPP-based system reaching clinical trials as a diagnostic imaging tool. The field has expanded from the original two classes (cationic and amphipathic) to include hydrophobic and cyclic CPPs, each with different strengths for drug delivery.","whyItMatters":"Cancer drugs often struggle to reach tumors effectively, and cell-penetrating peptides offer a promising solution by acting as molecular delivery vehicles. This review maps out what has worked so far and where the field is stuck, which is critical for directing future research toward approaches most likely to succeed in humans.","specificNumbers":"","methodology":"This was a comprehensive literature review examining published research on cell-penetrating peptides in cancer drug delivery. The authors analyzed studies based on the amino acid composition and sequences of CPPs, with a focus on measurable changes in tumor volume in mouse models. They reviewed individual CPPs and their derivatives, covering approaches from natural protein sequence selection to computer-based design methods.","limitations":"This is a review article, not an original study, so it summarizes existing research rather than generating new data. The reviewed studies were predominantly conducted in mice, and animal results frequently don't translate to humans. The review does not provide a systematic meta-analysis or statistical pooling of results across studies, making it difficult to quantify overall effectiveness."},{"rthcId":"RPEP-06705","title":"Systemic and Peripheral Mechanisms of Cortical Stimulation-Induced Analgesia and Refractoriness in a Rat Model of Neuropathic Pain.","authors":"Assis, Danielle V; Campos, Ana Carolina P; Paschoa, Amanda F N; Santos, Talita F; Fonoff, Erich T; Pagano, Rosana L","year":2023,"journal":"International journal of molecular sciences, 24(9)","doi":"10.3390/ijms24097796","pmid":"37175503","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"MCS inhibited hyperalgesia and allodynia in two-thirds of the rats, while one-third were refractory.","whyItMatters":"Understanding why some patients do not respond to MCS can help improve treatment strategies for chronic pain. This research could lead to better pain management options for individuals suffering from neuropathic pain.","specificNumbers":"","methodology":"The study used a rat model of sciatic neuropathy and measured the effects of MCS on pain and associated biological markers.","limitations":"The study was conducted in a rat model, which may not fully translate to human patients. Additionally, the sample size and specific biological markers examined may limit the generalizability of the findings."},{"rthcId":"RPEP-06706","title":"The Dimeric Peptide (KKYRYHLKPF)2K Shows Broad-Spectrum Antiviral Activity by Inhibiting Different Steps of Chikungunya and Zika Virus Infection.","authors":"Ayusso, Gabriela Miranda; Lima, Maria Letícia Duarte; da Silva Sanches, Paulo Ricardo; Santos, Igor Andrade; Martins, Daniel Oliveira Silva; da Conceição, Pâmela Jóyce Previdelli; Carvalho, Tamara; da Costa, Vivaldo Gomes; Bittar, Cíntia; Merits, Andres; Santos-Filho, Norival Alves; Cilli, Eduardo Maffud; Jardim, Ana Carolina Gomes; de Freitas Calmon, Marilia; Rahal, Paula","year":2023,"journal":"Viruses, 15(5)","doi":"10.3390/v15051168","pmid":"37243254","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"(p-BthTX-I)2K reduced Chikungunya virus entry and inhibited Zika virus replication in vitro.","whyItMatters":"There are currently no approved antiviral treatments for Chikungunya and Zika viruses, making this research significant for public health. The peptide's ability to target multiple stages of viral infection could lead to effective therapies.","specificNumbers":"","methodology":"The study assessed the peptide's antiviral activity in vitro against CHIKV and ZIKV in different cell lines.","limitations":"The study was conducted in vitro, so results may not directly translate to human treatments."},{"rthcId":"RPEP-06707","title":"Thymosin α1 modulated the immune landscape of COVID-19 patients revealed by single-cell RNA and TCR sequencing.","authors":"Bai, Han; Liang, Liyuan; Qi, Xin; Xu, Yao; Liu, Yijia; Ren, Doudou; Cai, Zeqiong; Mao, Weikang; Wang, Xiaorui; Qin, Hongyu; Hu, Fang; Shi, Bingyin","year":2023,"journal":"International immunopharmacology, 124(Pt B), 110983","doi":"10.1016/j.intimp.2023.110983","pmid":"37769533","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 33 COVID-19 patients and 11 healthy controls analyzed by scRNA-seq and TCR-seq:\n\n- CD3+ KLRD1+ NKT cells increased with Tα1 in COVID-19 (p = 0.024) and healthy controls (p = 0.016)\n- TBX21+ CD8+ NKT cells increased with Tα1 in COVID-19 (p = 0.010) and healthy controls (p = 0.031)\n- Tα1-treated NKT cells showed higher expression of KLRB1, PRF1 (perforin) and enrichment of NK cell cytotoxicity, chemokine signaling, and JAK-STAT pathways\n- Increased TRBV9-TRBJ1-1 T cell receptor pair in both groups after Tα1 treatment\n- 1,389 common CDR3 sequences between untreated COVID-19 and healthy, but 0 common sequences between treated groups — indicating Tα1 diversifies T cell clones\n- Tα1 promotes NKT cell activation and cytotoxicity through gene expression regulation","whyItMatters":"This is one of the most detailed studies of how thymosin alpha-1 modifies the immune system, using advanced single-cell technology to reveal changes at individual cell level. The finding that Tα1 enhances NKT killer cells and diversifies T cell receptors provides a molecular rationale for its use as an immunomodulator — not just in COVID-19 but potentially in other infections and in immunocompromised patients.","specificNumbers":"","methodology":"Peripheral blood mononuclear cells from 33 symptomatic COVID-19 patients (with and without Tα1 treatment) and 11 healthy controls (with and without Tα1) were analyzed using single-cell RNA sequencing (scRNA-seq) and T cell receptor sequencing (TCR-seq). Differential expression analysis and functional enrichment analysis were performed to identify immune changes mediated by Tα1.","limitations":"The sample size is small (44 total participants), limiting statistical power. The study is observational without randomization — patients who received Tα1 may have differed from those who didn't. The scRNA-seq analysis captures a snapshot at one time point, not the dynamic immune response over time. Clinical outcomes (symptom improvement, hospital stay, mortality) were not correlated with the immunological findings. The COVID-19 variants involved were not specified."},{"rthcId":"RPEP-06708","title":"An update on peptide-based therapies for type 2 diabetes and obesity.","authors":"Bailey, Clifford J; Flatt, Peter R; Conlon, J Michael","year":2023,"journal":"Peptides, 161, 170939","doi":"10.1016/j.peptides.2023.170939","pmid":"36608818","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide and tirzepatide show high efficacy in lowering glucose and weight.","whyItMatters":"These peptide therapies could revolutionize treatment options for millions suffering from type 2 diabetes and obesity. Their effectiveness may lead to better management of these chronic conditions.","specificNumbers":"","methodology":"The study reviews recent clinical trials and developments in peptide therapies for diabetes and obesity.","limitations":"The study primarily reviews existing therapies and does not present new experimental data."},{"rthcId":"RPEP-06709","title":"Preventing Respiratory Viral Diseases with Antimicrobial Peptide Master Regulators in the Lung Airway Habitat.","authors":"Baindara, Piyush; Ganguli, Sriradha; Chakraborty, Ranadhir; Mandal, Santi M","year":2023,"journal":"Clinics and practice, 13(1), 125-147","doi":"10.3390/clinpract13010012","pmid":"36648852","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The study details the expression and regulation of host defense peptides in the respiratory tract.","whyItMatters":"This research could lead to new strategies for preventing respiratory infections by enhancing the body's natural defenses.","specificNumbers":"","methodology":"The research involved a comprehensive review of host defense peptides in the respiratory system and their regulatory mechanisms.","limitations":"The study is primarily a review and does not include experimental data or clinical trials."},{"rthcId":"RPEP-06710","title":"Enhanced secretion of satiety-promoting gut hormones in healthy humans after consumption of white bread enriched with cellular chickpea flour: A randomized crossover study.","authors":"Bajka, Balazs H; Pinto, Ana M; Perez-Moral, Natalia; Saha, Shikha; Ryden, Peter; Ahn-Jarvis, Jennifer; van der Schoot, Alice; Bland, Catherine; Berry, Sarah E; Ellis, Peter R; Edwards, Cathrina H","year":2023,"journal":"The American journal of clinical nutrition, 117(3), 477-489","doi":"10.1016/j.ajcnut.2022.12.008","pmid":"36811474","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Bread enriched with 60% cellular chickpea powder (CCP) significantly increased postprandial GLP-1 and PYY responses compared to standard white bread (time × treatment, P = 0.001 for both hormones). The GLP-1 incremental area under the curve (iAUC) showed a mean difference of 3,101 pM/min (95% CI: 1,891–4,310; P-adjusted < 0.001) between the 60% and 0% CCP breads.\n\nThe 60% CCP bread also produced approximately 40% lower glucose iAUC (P-adjusted < 0.001) compared to regular white bread. In vitro studies confirmed that intact chickpea cells digest slowly, explaining the sustained hormone release and improved glycemic response.","whyItMatters":"GLP-1 is the same peptide hormone targeted by blockbuster weight-loss drugs like semaglutide (Ozempic/Wegovy). This study shows that a simple dietary modification — using intact chickpea cell flour in bread — can naturally boost GLP-1 and PYY release, potentially offering a food-based strategy for improving satiety and blood sugar control. This has implications for dietary approaches to obesity and cardiometabolic disease prevention.","specificNumbers":"","methodology":"This was a double-blind randomized crossover study with 20 healthy participants. Each participant consumed white bread with 0%, 30%, or 60% cellular chickpea powder on separate occasions (50g total starch per serving). Postprandial blood samples were collected to measure GLP-1, PYY, glucose, and insulin responses. Satiety scores were also collected. Complementary in vitro digestion studies were conducted to understand the mechanistic basis for the observed effects. The trial was registered at ClinicalTrials.gov (NCT03994276).","limitations":"The sample size was small (n=20), limiting statistical power for subgroup analyses. Only healthy participants were studied, so responses in people with obesity or diabetes may differ. The study measured acute postprandial responses over a single meal; long-term effects on weight or metabolic health were not assessed. The 60% chickpea flour bread may have different taste and texture that could affect real-world acceptability despite the double-blind design."},{"rthcId":"RPEP-06711","title":"Advances in Peptide-Based Hydrogel for Tissue Engineering.","authors":"Bakhtiary, Negar; Ghalandari, Behafarid; Ghorbani, Farnaz; Varma, Swastina Nath; Liu, Chaozong","year":2023,"journal":"Polymers, 15(5)","doi":"10.3390/polym15051068","pmid":"36904309","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies peptide-based hydrogels as leading biomaterials due to three key properties: tunable mechanical stability, high water content, and high biocompatibility. Key design parameters include pH sensitivity, amino acid composition within the peptide sequence, and cross-linking techniques. These hydrogels effectively mimic extracellular matrix proteins, providing the three-dimensional environment cells need to grow into functional tissue. Multiple types of peptide-based materials and their self-assembly mechanisms are discussed.","whyItMatters":"Tissue engineering could eliminate the need for organ donors and provide personalized repair materials for injuries. Peptide-based hydrogels are at the forefront of this field because they combine the tunability of synthetic materials with the biological compatibility of natural proteins. Understanding how to design and control these materials is essential for translating laboratory successes into clinical tissue engineering products.","specificNumbers":"","methodology":"Comprehensive review article examining the literature on peptide-based hydrogel design, self-assembly mechanisms, and tissue engineering applications. Covers various peptide structures, hydrogel formation conditions, and critical design parameters.","limitations":"As a review article, this paper synthesizes existing research without presenting new experimental data. The rapidly evolving field means some reviewed studies may have been superseded by newer work. The review covers a broad range of hydrogel types and applications without deep quantitative comparison of their performance. Translation from laboratory demonstrations to clinical products faces significant regulatory and manufacturing challenges not fully addressed."},{"rthcId":"RPEP-06712","title":"Thymosin beta-4 - A potential tool in healing middle ear lesions in adult mammals.","authors":"Bako, Peter; Lippai, Balint; Nagy, Jazmin; Kramer, Sofie; Kaszas, Balint; Tornoczki, Tamas; Bock-Marquette, Ildiko","year":2023,"journal":"International immunopharmacology, 116","doi":"10.1016/j.intimp.2023.109830","pmid":"38706788","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"TB4 affects epidermal and epithelial cell behavior, targeting local progenitor cells.","whyItMatters":"Finding effective treatments for chronic tympanic membrane perforations could significantly improve healing outcomes and reduce the need for surgical interventions.","specificNumbers":"","methodology":"The study involved treating harvested tympanic membranes from adult mice with TB4 or PBS, using collagen gel matrices and ex vivo explants to measure cell migration and proliferation.","limitations":"The study was conducted in vitro using mouse models, which may not fully translate to human applications."},{"rthcId":"RPEP-06713","title":"Lysosomal-Cleavable Peptide Linkers in Antibody-Drug Conjugates.","authors":"Balamkundu, Seetharamsing; Liu, Chuan-Fa","year":2023,"journal":"Biomedicines, 11(11)","doi":"10.3390/biomedicines11113080","pmid":"38002080","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"ValCitPABC linkers are stable in human plasma but cleaved by mouse and rat plasma enzymes.","whyItMatters":"Improving linker design in ADCs could lead to more effective cancer treatments with fewer side effects. Understanding the stability and cleavage of linkers is crucial for optimizing therapy.","specificNumbers":"","methodology":"The study is a review of recent advances in peptide linker design and structure-activity relationships in ADCs.","limitations":"The study primarily focuses on existing linkers and does not provide new experimental data or clinical outcomes."},{"rthcId":"RPEP-06714","title":"Development of a Potent Cyclic Peptide Inhibitor of the nNOS/PSD-95 Interaction.","authors":"Balboa, Javier R; Essig, Dominik J; Ma, Sana; Karer, Nichlas; Clemmensen, Louise S; Pedersen, Søren W; Joerger, Andreas C; Knapp, Stefan; Østergaard, Søren; Strømgaard, Kristian","year":2023,"journal":"Journal of medicinal chemistry, 66(1), 976-990","doi":"10.1021/acs.jmedchem.2c01803","pmid":"36580549","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Identified a potent cyclic peptide inhibitor with the highest reported affinity for the nNOS/PSD-95 interaction.","whyItMatters":"Disrupting the nNOS/PSD-95 interaction could lead to new treatments for acute ischemic stroke, a condition with limited therapeutic options.","specificNumbers":"","methodology":"The study involved designing cyclic peptide arrays and optimizing them to find effective inhibitors of the nNOS/PSD-95 complex.","limitations":"The study primarily focuses on peptide design and in vitro interactions, and further research is needed to assess efficacy in vivo."},{"rthcId":"RPEP-06715","title":"The Effect of Specific Bioactive Collagen Peptides on Tendon Remodeling during 15 wk of Lower Body Resistance Training.","authors":"Balshaw, Thomas G; Funnell, Mark P; McDermott, Emmet J; Maden-Wilkinson, Thomas M; Massey, Garry J; Abela, Sean; Quteishat, Btool; Edsey, Max; James, Lewis J; Folland, Jonathan P","year":2023,"journal":"Medicine and science in sports and exercise, 55(11), 2083-2095","doi":"10.1249/MSS.0000000000003242","pmid":"37436929","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"No significant differences in tendon adaptations were found between collagen peptide and placebo groups.","whyItMatters":"Understanding the effects of collagen peptides on tendon health can inform athletes and trainers about effective supplementation strategies. This study suggests that collagen peptides may not provide additional benefits over a placebo for tendon adaptations during resistance training.","specificNumbers":"","methodology":"The study was a double-blind, placebo-controlled trial involving 39 young men who were randomized to receive either collagen peptides or a placebo during a resistance training program.","limitations":"The study was limited to a specific population of young, healthy men, which may not represent other demographics. Additionally, the duration of the study may not capture long-term effects."},{"rthcId":"RPEP-06716","title":"Role of semaglutide in the treatment of nonalcoholic fatty liver disease or non-alcoholic steatohepatitis: A systematic review and meta-analysis.","authors":"Bandyopadhyay, Sanjay; Das, Saibal; Samajdar, Shambo Samrat; Joshi, Shashank R","year":2023,"journal":"Diabetes & metabolic syndrome, 17(10), 102849","doi":"10.1016/j.dsx.2023.102849","pmid":"37717295","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06717","title":"GLP-1 Receptor Agonists and Risk of Adverse Cerebrovascular Outcomes in Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.","authors":"Banerjee, Mainak; Pal, Rimesh; Mukhopadhyay, Satinath; Nair, Kirthana","year":2023,"journal":"The Journal of clinical endocrinology and metabolism, 108(7), 1806-1812","doi":"10.1210/clinem/dgad076","pmid":"36800286","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 receptor agonists reduced adverse cerebrovascular outcomes by 17% (RR 0.83, 95% CI 0.76–0.91, I²=0%) across 28 RCTs with 74,148 patients. Specifically, ischemic stroke was reduced by 27% (RR 0.73, 95% CI 0.60–0.89) and the composite of ischemic stroke/TIA by 24% (RR 0.76, 95% CI 0.65–0.90). Nonfatal stroke was reduced by 15% (RR 0.85, 95% CI 0.76–0.94), but reductions in fatal stroke (RR 0.80) and hemorrhagic stroke (RR 0.92) were not statistically significant.\n\nBenefits were statistically significant for dulaglutide and both subcutaneous and oral semaglutide. Patients with shorter diabetes duration and higher baseline kidney function (eGFR) showed greater benefit.","whyItMatters":"Stroke is a leading cause of death and disability in people with type 2 diabetes, who face double the stroke risk of the general population. Demonstrating that GLP-1 drugs specifically protect against ischemic stroke — not just cardiovascular events broadly — provides strong evidence for using these drugs in diabetes patients at cerebrovascular risk.","specificNumbers":"","methodology":"Systematic review and meta-analysis of 28 RCTs (≥24 weeks duration) in adults with type 2 diabetes, searching PubMed, Embase, Web of Science, Cochrane Library, and trial registries. Adjudicated cerebrovascular events were pooled using fixed-effects models. Subgroup analyses examined individual drugs, treatment duration, and baseline characteristics. Evidence quality was assessed using the GRADE framework.","limitations":"Individual trial-level data were not available, limiting the depth of subgroup analyses. The lack of significant effect on fatal stroke and hemorrhagic stroke may reflect limited power for these rarer outcomes. Treatment duration and comparators varied across trials. The interaction analyses for baseline characteristics used P < 0.1, a liberal threshold."},{"rthcId":"RPEP-06718","title":"Highlights on Cell-Penetrating Peptides and Polymer-Lipid Hybrid Nanoparticle: Overview and Therapeutic Applications for Targeted Anticancer Therapy.","authors":"Bangera, Pragathi Devanand; Kara, Divya Dhatri; Tanvi, Katikala; Tippavajhala, Vamshi Krishna; Rathnanand, Mahalaxmi","year":2023,"journal":"AAPS PharmSciTech, 24(5), 124","doi":"10.1208/s12249-023-02576-x","pmid":"37225901","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Surface modification of PLHNs with CPPs improves drug delivery efficiency.","whyItMatters":"Improving drug delivery systems can lead to more effective cancer treatments. This research could pave the way for better therapeutic strategies using nanotechnology.","specificNumbers":"","methodology":"This is a review study summarizing existing research on PLHNs and CPPs.","limitations":"As a review, it does not present original experimental data or clinical trial results."},{"rthcId":"RPEP-06719","title":"Intestinal epithelium penetration of liraglutide via cholic acid pre-complexation and zein/rhamnolipids nanocomposite delivery.","authors":"Bao, Xiaoyan; Qian, Kang; Xu, Mengjiao; Chen, Yi; Wang, Hao; Pan, Ting; Wang, Zhengyi; Yao, Ping; Lin, Li","year":2023,"journal":"Journal of nanobiotechnology, 21(1), 16","doi":"10.1186/s12951-022-01743-9","pmid":"36647125","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"LIRA/CA@Zein/RLs improved intestinal absorption and provided a significant hypoglycemic effect in mice.","whyItMatters":"Enhancing oral delivery of liraglutide could increase patient compliance and improve diabetes management. This research opens avenues for developing oral peptide therapies.","specificNumbers":"","methodology":"The study used molecular docking simulations, anti-solvent methods for nanoparticle formation, and in vivo testing in mice.","limitations":"The study was conducted in mice, and results may not directly translate to humans. Further clinical trials are needed."},{"rthcId":"RPEP-06720","title":"Systemic peptide amphiphile nanofiber delivery following subcutaneous injection.","authors":"Barlek, Mark H; Gillis, David C; Egner, Simon A; Maragos, Sophia L; Karver, Mark R; Stupp, Samuel I; Tsihlis, Nick D; Kibbe, Melina R","year":2023,"journal":"Biomaterials, 303, 122401","doi":"10.1016/j.biomaterials.2023.122401","pmid":"38006645","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06721","title":"Dosing Patterns of Dulaglutide and Semaglutide in Patients with Type 2 Diabetes in the United Kingdom and Germany: A Retrospective Cohort Study.","authors":"Barrett, Annabel; Debackere, Nele; Ribeiro, Anderson; Keapoletswe, Karabo; Zingel, Rebecca; Coles, Briana","year":2023,"journal":"Advances in therapy, 40(8), 3446-3464","doi":"10.1007/s12325-023-02540-y","pmid":"37286889","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In Germany, 65.6% of dulaglutide users and 39.2% of semaglutide users received the most common dosages at 12 months.","whyItMatters":"Understanding dosing patterns helps inform healthcare providers about treatment trends and can guide future prescribing practices. It also highlights the need for ongoing research into the effectiveness of newer medication formulations.","specificNumbers":"","methodology":"This retrospective cohort study used prescription data to analyze dosing patterns among adults with type 2 diabetes over a 12-month period.","limitations":"The study is retrospective and may not capture all clinical outcomes or patient experiences."},{"rthcId":"RPEP-06722","title":"Validation of Freshly Isolated Rat Renal Cells as a Tool for Preclinical Assessment of Radiolabeled Receptor-Specific Peptide Uptake in the Kidney.","authors":"Barta, Pavel; Nachtigal, Petr; Maixnerova, Jana; Zemankova, Lenka; Trejtnar, Frantisek","year":2023,"journal":"Pharmaceuticals (Basel, Switzerland), 16(5)","doi":"10.3390/ph16050696","pmid":"37242479","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Freshly isolated rat renal cells were validated as an effective screening tool for evaluating kidney uptake of radiolabeled peptides. The cells maintained functional megalin transport systems (a key driver of renal peptide accumulation), confirmed by colocalization experiments showing proximal tubular cells bearing megalin. The method was successfully tested with indium-111 and lutetium-177 labeled analogs of somatostatin and gastrin, demonstrating its applicability for comparative renal accumulation studies.","whyItMatters":"Kidney accumulation is one of the biggest obstacles to using radiolabeled peptides in nuclear medicine for cancer imaging and therapy. Having a reliable in vitro screening tool to predict and compare kidney uptake early in development could accelerate the design of safer peptide radiopharmaceuticals with reduced nephrotoxicity.","specificNumbers":"Somatostatin and gastrin analogs tested · indium-111 and lutetium-177 radiolabels · megalin transport system confirmed · proximal tubular cell markers validated","methodology":"Rat renal cells were isolated by collagenase digestion. Megalin expression was compared across cell models via Western blotting. Proximal tubular cells were confirmed by immunohistochemistry with specific markers and megalin colocalization. The system was validated by measuring uptake of compounds with known renal accumulation patterns, then tested with radiolabeled somatostatin and gastrin peptide analogs.","limitations":"Rat renal cells may not perfectly model human kidney peptide handling. Freshly isolated cells have a limited lifespan, which may affect reproducibility and throughput. The study validates the method but does not yet use it to compare or optimize novel peptide candidates. Translation to human renal cell models would strengthen the platform."},{"rthcId":"RPEP-06723","title":"Rainbow Trout (Oncorhynchus mykiss) as Source of Multifunctional Peptides with Antioxidant, ACE and DPP-IV Inhibitory Activities.","authors":"Bartolomei, Martina; Cropotova, Janna; Bollati, Carlotta; Kvangarsnes, Kristine; d'Adduzio, Lorenza; Li, Jianqiang; Boschin, Giovanna; Lammi, Carmen","year":2023,"journal":"Nutrients, 15(4)","doi":"10.3390/nu15040829","pmid":"36839187","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Peptides derived from enzymatic hydrolysis of rainbow trout protein demonstrated three types of biological activity in vitro: antioxidant effects (confirmed by DPPH, FRAP, ORAC, and ABTS assays), dose-dependent ACE inhibition (relevant to blood pressure), and DPP-IV inhibition of up to 27.57 ± 3.7% at 5 mg/mL (relevant to blood sugar regulation). These activities were confirmed at the cellular level using human intestinal Caco-2 cells, where the hydrolysate reduced hydrogen peroxide-induced reactive oxygen species and lipid peroxidation.","whyItMatters":"Finding food-derived peptides with multiple health-promoting activities opens the door to functional foods and nutraceuticals that could help manage blood pressure, blood sugar, and oxidative stress simultaneously. Fish processing generates large amounts of protein-rich byproducts, and converting these into bioactive peptides adds value while potentially creating accessible health ingredients.","specificNumbers":"","methodology":"Rainbow trout (Oncorhynchus mykiss) protein was subjected to enzymatic hydrolysis to generate low molecular weight peptide fractions. Antioxidant activity was tested using four in vitro assays (DPPH, FRAP, ORAC, ABTS). ACE and DPP-IV inhibitory activities were measured in cell-free assays showing dose-dependent inhibition. Cellular-level validation used human intestinal Caco-2 cells to assess ROS reduction, lipid peroxidation, and DPP-IV enzyme activity inhibition.","limitations":"All experiments were in vitro — there is no evidence that these peptides survive digestion intact or produce meaningful effects when consumed orally by humans. The DPP-IV inhibition of ~28% at 5 mg/mL is modest compared to pharmaceutical DPP-IV inhibitors. The specific peptide sequences responsible for the activities were not identified. No animal or human feeding studies were conducted."},{"rthcId":"RPEP-06724","title":"Improvement of Left Ventricular Global Longitudinal Strain after 6-Month Therapy with GLP-1RAs Semaglutide and Dulaglutide in Type 2 Diabetes Mellitus: A Pilot Study.","authors":"Basile, Paolo; Guaricci, Andrea Igoren; Piazzolla, Giuseppina; Volpe, Sara; Vozza, Alfredo; Benedetto, Marina; Carella, Maria Cristina; Santoro, Daniela; Monitillo, Francesco; Baggiano, Andrea; Mushtaq, Saima; Fusini, Laura; Fazzari, Fabio; Forleo, Cinzia; Ribecco, Nunziata; Pontone, Gianluca; Sabbà, Carlo; Ciccone, Marco Matteo","year":2023,"journal":"Journal of clinical medicine, 12(4)","doi":"10.3390/jcm12041586","pmid":"36836121","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Improvement in left ventricular global longitudinal strain by -1.4 ± 1.1% after 6 months (p < 0.001).","whyItMatters":"Improving heart function in diabetes patients can reduce cardiovascular risks, making GLP-1 medications potentially beneficial beyond glucose control.","specificNumbers":"","methodology":"An observational, prospective study with 22 patients measuring echocardiographic parameters before and after treatment.","limitations":"The study had a small sample size and was observational, which limits the ability to generalize findings."},{"rthcId":"RPEP-06725","title":"Gender differences in weight gain during attempted and successful smoking cessation on dulaglutide treatment: a predefined secondary analysis of a randomised trial.","authors":"Baur, Fabienne; Atila, Cihan; Lengsfeld, Sophia; Burkard, Thilo; Meienberg, Andrea; Bathelt, Cemile; Christ-Crain, Mirjam; Winzeler, Bettina","year":2023,"journal":"BMJ nutrition, prevention & health, 6(2), 301-309","doi":"10.1136/bmjnph-2023-000781","pmid":"38264360","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Women on dulaglutide had only 1% substantial weight gain compared to 24% on placebo (p<0.001).","whyItMatters":"Understanding gender differences in weight gain during smoking cessation can inform treatment strategies and improve outcomes for women, who may face unique challenges.","specificNumbers":"","methodology":"The study was a predefined secondary analysis of a randomized, placebo-controlled trial involving 255 daily smokers over 12 weeks.","limitations":"The study was limited to a specific population and may not generalize to all smokers or other demographics."},{"rthcId":"RPEP-06726","title":"The Role of Substance P Receptor Antagonists in Allergic Rhinitis: Ovalbumin-Induced Rat Model.","authors":"Becerik, Çağrı; Karaca, Çiğdem T; Özcan, Zühal; Kul, Selim; Toros, Sema Z","year":2023,"journal":"The Laryngoscope, 133(11), 2891-2897","doi":"10.1002/lary.30628","pmid":"36856158","tags":[],"studyType":"animal-study","evidenceStrength":"low","keyFinding":"In an ovalbumin-induced allergic rhinitis rat model, aprepitant (a substance P receptor antagonist) failed to reduce nasal symptoms like scratching and sneezing, while antihistamines and leukotriene receptor antagonists (LTRA) significantly improved those symptoms.\n\nHowever, aprepitant did produce histopathological changes — it significantly reduced pseudostratification (abnormal cell layering) in the laryngeal mucosa compared to untreated allergic rats. The study also found that the allergic rhinitis model produced measurable allergic changes in the larynx, not just the nose.","whyItMatters":"Substance P is a neuropeptide that drives inflammation and secretion in the airways, making it a logical drug target for allergic rhinitis. This study shows that blocking substance P with aprepitant changes tissue architecture but doesn't relieve nasal symptoms — suggesting substance P plays a structural rather than symptomatic role in airway allergy, and that current antihistamines and LTRAs remain more effective for symptom relief.","specificNumbers":"34 rats · 5 groups · Aprepitant: no effect on nasal symptoms · Significant reduction in laryngeal pseudostratification vs allergy group","methodology":"Researchers induced allergic rhinitis in 34 female Sprague Dawley rats (8–12 weeks old) using ovalbumin sensitization. The rats were divided into 5 groups and treated with aprepitant, antihistamine, leukotriene receptor antagonist, or controls. Nasal symptoms (scratching, sneezing) were scored by observation, and nasal and laryngeal tissue was examined histopathologically after treatment.","limitations":"Animal model results may not translate to humans. Small sample size (34 rats across 5 groups means ~7 per group). The study only assessed short-term effects and tissue changes, not long-term clinical outcomes. Aprepitant dosing in rats may not reflect optimal human dosing."},{"rthcId":"RPEP-06727","title":"Complement-regulatory biomaterial coatings: Activity and selectivity profile of the factor H-binding peptide 5C6.","authors":"Bechtler, Clément; Koutsogiannaki, Sophia; Umnyakova, Ekaterina; Hamid, Amal; Gautam, Avneesh; Sarigiannis, Yiannis; Pouw, Richard B; Lamers, Christina; Rabbani, Said; Schmidt, Christoph Q; Lambris, John D; Ricklin, Daniel","year":2023,"journal":"Acta biomaterialia, 155, 123-138","doi":"10.1016/j.actbio.2022.10.055","pmid":"36328123","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"5C6 selectively binds to factor H, enhancing its recruitment and reducing C3 opsonization.","whyItMatters":"Understanding how to control immune responses to biomaterials is crucial for improving medical treatments. This research could lead to safer and more effective biomaterials in clinical settings.","specificNumbers":"","methodology":"The study used microparticle-based assays to evaluate the binding of the peptide 5C6 to factor H and its effects on complement activation.","limitations":"The study primarily focuses on in vitro assays, and the results may not fully translate to in vivo conditions."},{"rthcId":"RPEP-06728","title":"A Comprehensive Technology Platform for the Rapid Discovery of Peptide Inhibitors against SARS-CoV-2 Pseudovirus Infection.","authors":"Beeg, Marten; Baroni, Sara; Piotti, Arianna; Porta, Alessia; De Luigi, Ada; Cagnotto, Alfredo; Gobbi, Marco; Diomede, Luisa; Salmona, Mario","year":2023,"journal":"International journal of molecular sciences, 24(15)","doi":"10.3390/ijms241512146","pmid":"37569522","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The cyclic peptide c9_05 effectively inhibited pseudovirus transduction in HEK293 cells, but showed negligible efficacy against the Omicron variant.","whyItMatters":"This research could lead to new treatments for COVID-19 by targeting viral entry mechanisms. The platform may also be useful for addressing other emerging viral threats.","specificNumbers":"","methodology":"The study involved designing cyclic peptides, synthesizing them, and validating their effectiveness through ELISA and Surface Plasmon Resonance assays.","limitations":"The study's findings may not fully translate to human applications, and the efficacy against certain variants was limited."},{"rthcId":"RPEP-06729","title":"COVID-19 and beyond: Reassessing the role of thymosin alpha1 in lung infections.","authors":"Bellet, Marina M; Renga, Giorgia; Pariano, Marilena; Stincardini, Claudia; D'Onofrio, Fiorella; Goldstein, Allan L; Garaci, Enrico; Romani, Luigina; Costantini, Claudio","year":2023,"journal":"International immunopharmacology, 117, 109949","doi":"10.1016/j.intimp.2023.109949","pmid":"36881979","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Thymosin alpha1 may serve as a therapeutic agent for lung infections by balancing immune responses.","whyItMatters":"Understanding how thymosin alpha1 works could lead to new therapies for lung infections, which remain a significant health threat. This research could improve patient outcomes in future respiratory outbreaks.","specificNumbers":"","methodology":"This is a review article that synthesizes recent findings on thymosin alpha1 and its role in immune regulation during lung infections.","limitations":"As a review, it does not present original experimental data and relies on existing literature, which may vary in quality."},{"rthcId":"RPEP-06730","title":"Evaluating potential predictors of weight loss response to liraglutide in adolescents with obesity: A post hoc analysis of the randomized, placebo-controlled SCALE Teens trial.","authors":"Bensignor, Megan O; Bramante, Carolyn T; Bomberg, Eric M; Fox, Claudia K; Hale, Paula M; Kelly, Aaron S; Mamadi, Rashmi; Prabhu, Nandana; Harder-Lauridsen, Nina M; Gross, Amy C","year":2023,"journal":"Pediatric obesity, 18(9), e13061","doi":"10.1111/ijpo.13061","pmid":"37264767","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06731","title":"Unraveling and profiling Tityus bahiensis venom: Biochemical analyses of the major toxins.","authors":"Beraldo-Neto, Emidio; Vigerelli, Hugo; Coelho, Guilherme Rabelo; da Silva, Daiane Laise; Nencioni, Ana Leonor Abrahao; Pimenta, Daniel Carvalho","year":2023,"journal":"Journal of proteomics, 274, 104824","doi":"10.1016/j.jprot.2023.104824","pmid":"36646272","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The study identified a variety of toxins, including phospholipases and angiotensin-converting enzymes, previously unreported in scorpion venoms.","whyItMatters":"Understanding the composition of Tityus bahiensis venom can help in developing treatments for scorpion stings and enhance knowledge of venomous species.","specificNumbers":"","methodology":"The researchers employed chromatographic separation and proteomic analyses to characterize the venom's components.","limitations":"The study focuses solely on one species and may not represent the venom composition of other scorpions."},{"rthcId":"RPEP-06732","title":"Evaluation in pig of an intestinal administration device for oral peptide delivery.","authors":"Berg, Staffan; Uggla, Teresia; Antonsson, Malin; Nunes, Sandro Filipe; Englund, Maria; Rosengren, Louise; Fahraj, Masoud; Wu, Xiaoqiu; Govender, Rydvikha; Söderberg, Magnus; Janzén, David; Van Zuydam, Natalie; Hugerth, Andreas; Larsson, Anette; Abrahmsén-Alami, Susanna; Abrahamsson, Bertil; Davies, Nigel; Bergström, Christel A S","year":2023,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 353, 792-801","doi":"10.1016/j.jconrel.2022.12.011","pmid":"36493948","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Bioavailability of MEDI7219 was 2.5-3.8% with lower variability using the IAD.","whyItMatters":"Improving peptide delivery methods can enhance therapeutic effectiveness. This study suggests that controlling drug release location may help reduce variability in absorption.","specificNumbers":"","methodology":"The study used a pig model to compare the new intestinal administration device with enteric coated capsules and a solution.","limitations":"The study was conducted in pigs, which may not fully represent human physiology, and the bioavailability improvements were minimal."},{"rthcId":"RPEP-06733","title":"Peptide derived C. striata albumin as a natural angiotensin-converting enzyme inhibitor.","authors":"Berlian, Guntur; Riani, Catur; Kurniati, Neng Fisheri; Rachmawati, Heni","year":2023,"journal":"Heliyon, 9(5), e15958","doi":"10.1016/j.heliyon.2023.e15958","pmid":"37187901","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Albumin was isolated from C. striata fish extract using the Cohn Process, yielding 3.8 ± 2.1% in the most albumin-rich fraction (Fraction-5). Two protein bands of approximately 10 and 13 kDa were identified by tricine-SDS PAGE.\n\nACE inhibition activity increased across fractions, ranging from 7.09% to 22.99%. The highest ACE-inhibiting activity was found in peptides produced by alcalase hydrolysis with molecular size under 3 kDa, achieving an IC50 of 36.93 μg/mL. This was statistically significant compared to non-hydrolyzed fractions, supporting the potential of C. striata albumin-derived peptides as natural antihypertensive agents.","whyItMatters":"Hypertension affects over a billion people worldwide, and many patients experience side effects from synthetic ACE inhibitors. Identifying natural peptide-based alternatives from food sources like fish could provide new options for blood pressure management with potentially fewer side effects.","specificNumbers":"","methodology":"Albumin was isolated from C. striata fish extract using the Cohn fractionation process. The protein was then broken down into peptides through enzymatic hydrolysis using alcalase. Proteins were characterized using tricine-SDS PAGE gel electrophoresis, and ACE inhibition was measured using an in vitro assay.","limitations":"This was an in vitro study only — ACE inhibition in a test tube does not guarantee the same effect in living organisms. The peptides' stability during digestion, bioavailability, and actual blood pressure-lowering effect in animals or humans remain unknown. The albumin identification was tentative, based on molecular weight rather than definitive sequencing."},{"rthcId":"RPEP-06734","title":"Glucagon-like Peptide-1 Receptor Agonists for the Treatment of Type 2 Diabetes in Youth.","authors":"Berman, Casey; Vidmar, Alaina P; Chao, Lily C","year":2023,"journal":"TouchREVIEWS in endocrinology, 19(1), 38-45","doi":"10.17925/EE.2023.19.1.38","pmid":"37313232","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1RAs effectively reduce haemoglobin A1c and promote weight loss in youth with type 2 diabetes.","whyItMatters":"With rising rates of type 2 diabetes in youth, effective treatment options are crucial. Understanding GLP-1RAs can improve management strategies and outcomes for young patients.","specificNumbers":"","methodology":"This is a review of recent clinical trials and existing literature on GLP-1RAs in pediatric diabetes management.","limitations":"The review highlights limited pediatric clinical trial data and the need for further studies to confirm findings."},{"rthcId":"RPEP-06735","title":"Fast Self-Assembly Dynamics of a β-Sheet Peptide Soft Material.","authors":"Bertouille, Jolien; Kasas, Sandor; Martin, Charlotte; Hennecke, Ulrich; Ballet, Steven; Willaert, Ronnie G","year":2023,"journal":"Small (Weinheim an der Bergstrasse, Germany), 19(20), e2206795","doi":"10.1002/smll.202206795","pmid":"36807731","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The peptide KFE8 forms a fast-growing fibrillar network at a solid-liquid interface, while a slower nanotube network forms in bulk solution.","whyItMatters":"These findings could enhance the design of peptide-based materials for medical applications, providing insights into how to control their properties.","specificNumbers":"","methodology":"The study utilized high-speed atomic force microscopy (HS-AFM) to observe the self-assembly dynamics of the peptide in real-time.","limitations":"The study focuses on a single peptide and its specific conditions, which may not fully represent other peptides or real-world applications."},{"rthcId":"RPEP-06736","title":"Purification, molecular docking and in vivo analyses of novel angiotensin-converting enzyme inhibitory peptides from protein hydrolysate of moth bean (Vigna aconitifolia (Jacq.) Màrechal) seeds.","authors":"Bhadkaria, Amita; Narvekar, Dakshita Tanaji; Nagar, D P; Sah, Sangeeta Pilkwal; Srivastava, Nidhi; Bhagyawant, Sameer Suresh","year":2023,"journal":"International journal of biological macromolecules, 230, 123138","doi":"10.1016/j.ijbiomac.2023.123138","pmid":"36610577","tags":["bioactive-peptides"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Researchers extracted peptides from moth bean seeds using six different enzymes and found that alcalase produced the most effective ACE-inhibiting fragments. The most potent peptide fraction inhibited ACE at just 11.19 ± 0.15 μg/mL. Four specific peptides (IAWDFR, ADLPGLK, DKPWWPK, and AVIPNAPNLR) were identified through mass spectrometry, with molecular docking showing two bind to active sites and two to non-active sites of the ACE molecule.\n\nIn live testing, the moth bean protein hydrolysate lowered systolic blood pressure in hypertensive rats from 155 ± 3.13 mmHg (control) to 125 ± 0.76 mmHg — a 30 mmHg reduction.","whyItMatters":"ACE inhibitor drugs are a cornerstone of blood pressure treatment but come with side effects like dry cough. Finding natural ACE-inhibiting peptides in common food legumes could eventually lead to functional foods or nutraceuticals that help manage blood pressure with fewer side effects.","specificNumbers":"ACE inhibition IC50: 11.19 ± 0.15 μg/mL · SBP reduced: 155 → 125 mmHg · 30 mmHg drop · 4 peptides identified","methodology":"Moth bean seed protein was extracted and hydrolyzed with six enzymes (alcalase, chymotrypsin, flavourzyme, papain, pepsin, trypsin). The most active hydrolysate was purified by FPLC and analyzed by mass spectrometry. Molecular docking simulated peptide binding to ACE. In vivo testing used dexamethasone-induced hypertensive rats.","limitations":"This is an animal study — the blood pressure effects were shown in rats with chemically induced hypertension, which may not translate directly to human essential hypertension. The peptides were tested as a hydrolysate mixture rather than as isolated pure peptides in the in vivo portion. No toxicity or long-term safety data was reported."},{"rthcId":"RPEP-06737","title":"Niacinamide enhances cathelicidin mediated SARS-CoV-2 membrane disruption.","authors":"Bhatt, Tanay; Dam, Binita; Khedkar, Sneha Uday; Lall, Sahil; Pandey, Subhashini; Kataria, Sunny; Ajnabi, Johan; Gulzar, Shah-E-Jahan; Dias, Paul M; Waskar, Morris; Raut, Janhavi; Sundaramurthy, Varadharajan; Vemula, Praveen Kumar; Ghatlia, Naresh; Majumdar, Amitabha; Jamora, Colin","year":2023,"journal":"Frontiers in immunology, 14, 1255478","doi":"10.3389/fimmu.2023.1255478","pmid":"38022563","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Human cathelicidin LL-37 neutralized multiple SARS-CoV-2 variants through direct disruption of the viral membrane, as confirmed by biophysical and computational studies. Niacinamide enhanced this antiviral activity through its hydrotropic action, which may increase the bioavailability of LL-37.\n\nClinically, an inverse correlation was observed between LL-37 levels and COVID-19 disease severity in patients — those with higher LL-37 levels had milder disease. The combination of niacinamide and LL-37 showed potent antiviral activity against various SARS-CoV-2 variants, including those that escape vaccine-generated immunity.","whyItMatters":"As SARS-CoV-2 continues to evolve and potentially escape vaccine immunity, strategies that harness the body's innate defenses offer a variant-agnostic approach. LL-37 targets the viral membrane itself — a structural feature shared across all variants — rather than the spike protein that vaccines target and that mutates frequently. Niacinamide is a cheap, widely available vitamin, making this combination potentially accessible worldwide.","specificNumbers":"","methodology":"The study combined multiple approaches: biophysical experiments to test LL-37's ability to disrupt SARS-CoV-2 membranes, computational modeling to understand the mechanism of interaction, clinical correlation analysis of LL-37 levels versus COVID-19 severity in patients, and testing of niacinamide's ability to enhance LL-37's antiviral activity across multiple viral variants.","limitations":"The primary findings are laboratory-based (in vitro and computational), not from a clinical trial testing niacinamide + LL-37 as a treatment. The clinical correlation between LL-37 levels and disease severity is observational and cannot prove causation. The study does not demonstrate that taking niacinamide supplements would raise LL-37 levels enough to provide clinical protection. The mechanism by which niacinamide increases LL-37 bioavailability needs further characterization."},{"rthcId":"RPEP-06738","title":"Efficacy and safety of the ghrelin-O-acyltransferase inhibitor BI 1356225 in overweight/obesity: Data from two Phase I, randomised, placebo-controlled studies.","authors":"Bianzano, Susanna; Henrich, Andrea; Herich, Lena; Kalsch, Brigitte; Sarubbi, Donald; Seitz, Friedeborg; Forst, Thomas","year":2023,"journal":"Metabolism: clinical and experimental, 143, 155550","doi":"10.1016/j.metabol.2023.155550","pmid":"36958671","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BI 1356225 reduced active ghrelin levels by over 80%, but no significant weight loss was observed.","whyItMatters":"Understanding how to effectively manage obesity is crucial given its health implications. This study highlights that simply reducing appetite-related hormones may not be enough for weight loss.","specificNumbers":"","methodology":"The study included two Phase I trials: one tested single doses of BI 1356225 in healthy males, and the other tested multiple doses in overweight/obese adults over 28 days.","limitations":"The studies were short (28 days) and did not assess long-term effects or weight loss outcomes."},{"rthcId":"RPEP-06739","title":"Structural, spectroscopic, molecular docking, ADME, molecular dynamics studies of Val-Trp dipeptide.","authors":"Bicak, Bilge","year":2023,"journal":"Journal of biomolecular structure & dynamics, 41(23), 13873-13890","doi":"10.1080/07391102.2023.2183041","pmid":"36843537","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Val-Trp dipeptide demonstrated favorable interactions with ACE and AT1R, indicating its potential as an antihypertensive agent.","whyItMatters":"Understanding the properties of Val-Trp could lead to new treatments for hypertension, a major health concern. This research contributes to the development of peptide-based therapies.","specificNumbers":"","methodology":"The study employed molecular mechanical and quantum mechanical methods, including DFT calculations, spectroscopic techniques, molecular docking, and molecular dynamics simulations.","limitations":"The study primarily focuses on in vitro analyses, and further research is needed to confirm efficacy in vivo."},{"rthcId":"RPEP-06740","title":"Can mesenchymal stem/stromal cells and their secretomes combat bacterial persisters?","authors":"Bicer, Mesude; Fidan, Ozkan","year":2023,"journal":"World journal of microbiology & biotechnology, 39(10), 276","doi":"10.1007/s11274-023-03725-x","pmid":"37567959","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"MSCs and their secretomes show promise in enhancing antimicrobial activity against persister bacteria.","whyItMatters":"With rising antibiotic resistance, exploring MSCs as a treatment could provide new options for difficult infections. This approach may help address a critical gap in current medical treatments.","specificNumbers":"","methodology":"The study is a review of existing literature on the antimicrobial effects of MSCs and their secreted components.","limitations":"The review does not provide new experimental data and relies on existing literature, which may vary in quality."},{"rthcId":"RPEP-06741","title":"Mechanistic Insights into Hyaluronic Acid Induced Peptide Nanofiber Organization in Supramolecular Hydrogels.","authors":"Bigo Simon, Alexis; Fores, Jennifer Rodon; Criado-Gonzalez, Miryam; Blandin, Lucille; Runser, Jean-Yves; Senger, Bernard; Fleith, Guillaume; Schmutz, Marc; Schurhammer, Rachel; Chaumont, Alain; Schaaf, Pierre; Combet, Jérôme; Jierry, Loïc","year":2023,"journal":"Biomacromolecules, 24(8), 3794-3805","doi":"10.1021/acs.biomac.3c00445","pmid":"37535455","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Hyaluronic acid leads to the formation of peptide bundles with a mean distance of 117 Å at high concentrations.","whyItMatters":"Understanding how polysaccharides like HA influence peptide organization can enhance the development of biomaterials for medical applications. This knowledge may lead to improved tissue engineering strategies.","specificNumbers":"","methodology":"The study utilized fluorescence recovery after photobleaching (FRAP) and small-angle X-ray scattering (SAXS) to analyze the interactions and organization of peptide fibers in the presence of hyaluronic acid.","limitations":"The study focuses on a specific peptide and polysaccharide interaction, which may not be generalizable to all biomaterials."},{"rthcId":"RPEP-06742","title":"Stereoisomer-Dependent Membrane Association and Capacity for Insulin Delivery Facilitated by Penetratin.","authors":"Birch, Ditlev; Sayers, Edward J; Christensen, Malene V; Jones, Arwyn T; Franzyk, Henrik; Nielsen, Hanne M","year":2023,"journal":"Pharmaceutics, 15(6)","doi":"10.3390/pharmaceutics15061672","pmid":"37376119","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"D-PEN increased transepithelial delivery of insulin by approximately four-fold compared to l-PEN.","whyItMatters":"Improving drug delivery methods can enhance the effectiveness of treatments, particularly for hydrophilic drugs. This research highlights the potential of peptide modifications to optimize therapeutic outcomes.","specificNumbers":"","methodology":"The study compared the membrane association and cellular uptake of all-L and all-D enantiomers of penetratin using various cell models and drug cargos.","limitations":"The study focused on specific cell models and may not fully represent human physiology. The effects on hydrophobic drugs were not significant."},{"rthcId":"RPEP-06743","title":"Influence of specific collagen peptides and 12-week concurrent training on recovery-related biomechanical characteristics following exercise-induced muscle damage-A randomized controlled trial.","authors":"Bischof, Kevin; Stafilidis, Savvas; Bundschuh, Larissa; Oesser, Steffen; Baca, Arnold; König, Daniel","year":2023,"journal":"Frontiers in nutrition, 10, 1266056","doi":"10.3389/fnut.2023.1266056","pmid":"38035363","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Participants taking collagen peptides showed faster recovery in maximum voluntary contraction and rate of force development compared to placebo.","whyItMatters":"This research suggests that collagen peptides may enhance muscle recovery, which is important for athletes and those engaging in regular exercise. Improved recovery can lead to better performance and reduced injury risk.","specificNumbers":"","methodology":"A randomized controlled trial with 55 participants assigned to either collagen peptides or placebo, combined with a 12-week concurrent training program.","limitations":"The study focused only on male participants and did not assess long-term effects beyond the 12-week period."},{"rthcId":"RPEP-06744","title":"Management of Poststroke Hyperglycemia: Results of the TEXAIS Randomized Clinical Trial.","authors":"Bladin, Christopher F; Wah Cheung, Ngai; Dewey, Helen M; Churilov, Leonid; Middleton, Sandy; Thijs, Vincent; Ekinci, Elif; Levi, Christopher R; Lindley, Richard; Donnan, Geoffrey A; Parsons, Mark W; Meretoja, Atte; Tiainen, Marjaana; Choi, Philip M C; Cordato, Dennis; Brown, Helen; Campbell, Bruce C V; Davis, Stephen M; Cloud, Geoffrey; Grimley, Rohan; Lee-Archer, Matthew; Ghia, Darshan; Sanders, Lauren; Markus, Romesh; Muller, Claire; Salvaris, Patrick; Wu, Teddy; Fink, John","year":2023,"journal":"Stroke, 54(12), 2962-2971","doi":"10.1161/STROKEAHA.123.044568","pmid":"38011235","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Exenatide reduced hyperglycemic events without causing hypoglycemia, but did not improve neurological outcomes.","whyItMatters":"Managing blood sugar levels after a stroke is crucial for recovery, and this study shows that exenatide can help without the risk of low blood sugar.","specificNumbers":"","methodology":"The TEXAIS trial was a phase 2 randomized clinical trial comparing exenatide to standard care in acute ischemic stroke patients.","limitations":"The study was stopped early due to COVID-19, limiting the sample size and potential findings."},{"rthcId":"RPEP-06745","title":"Toward tryptathionine-stapled one-bead-one-compound (OBOC) libraries: solid phase synthesis of a bioactive octretoate analog.","authors":"Blanc, Antoine; Todorovic, Mihajlo; Dude, Iulia; Merkens, Helen; Bénard, François; Perrin, David M","year":2023,"journal":"Organic & biomolecular chemistry, 21(40), 8112-8116","doi":"10.1039/d3ob01378b","pmid":"37772608","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The new Ttn-TATE analog successfully bound to somatostatin receptor subtype-2.","whyItMatters":"This research could lead to more effective diagnostic and therapeutic options for neuroendocrine tumors, which are often difficult to treat.","specificNumbers":"","methodology":"The study utilized solid-phase synthesis to create the Ttn-stapled peptide and employed fluorescent labeling for validation.","limitations":"The study primarily focuses on laboratory synthesis and validation, and further research is needed to assess clinical applicability."},{"rthcId":"RPEP-06746","title":"Effectiveness and Safety of Chronic Migraine Preventive Treatments: A Systematic Literature Review.","authors":"Blumenfeld, Andrew M; Kaur, Gavneet; Mahajan, Anadi; Shukla, Hemlata; Sommer, Katherine; Tung, Amy; Knievel, Kerry L","year":2023,"journal":"Pain and therapy, 12(1), 251-274","doi":"10.1007/s40122-022-00452-3","pmid":"36417165","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across real-world studies published between 2010 and 2020:\n\n• OnabotulinumtoxinA: 55 studies with long-term data (>1 year, up to 3 years). Substantial evidence for reducing headache number/frequency, decreasing acute medication use, and improving well-being and daily activity.\n\n• Erenumab (CGRP mAb): 6 studies with data up to 6 months. More limited evidence showing benefits for the same parameters.\n\n• Multiple CGRP mAbs: 1 study with data up to 12 months. Single study suggesting reduced headache frequency and impact.\n\n• Topiramate: 1 study with data up to 3 months. Single study suggesting decreased headache frequency.\n\nOnabotulinumtoxinA was the only treatment with long-term safety data from real-world settings reporting treatment-related adverse events.","whyItMatters":"Chronic migraine affects millions of people and choosing the right preventive treatment requires understanding not just clinical trial results but how treatments perform in everyday clinical practice. This review highlights a critical reality: while CGRP antibodies generated excitement at launch, Botox had far more real-world evidence supporting its effectiveness and safety. This information is essential for shared decision-making between patients and providers.","specificNumbers":"","methodology":"Systematic literature review searching MEDLINE, Embase, and the Cochrane Library, supplemented by back-referencing and additional searches, for publications from January 2010 to February 2020. Studies were screened, data extracted, and quality assessed. Results were narratively synthesized. Search criteria included all preventive medications for chronic migraine in adults.","limitations":"The search ended in February 2020, missing several years of rapidly accumulating CGRP antibody real-world data. The massive imbalance in available studies (55 for Botox vs 6 for erenumab) reflects time on market rather than relative effectiveness. The review did not include head-to-head real-world comparisons. Publication bias may favor positive Botox outcomes given its longer history. Quality of included real-world studies varied considerably."},{"rthcId":"RPEP-06747","title":"Structure-function-guided design of synthetic peptides with anti-infective activity derived from wasp venom.","authors":"Boaro, Andreia; Ageitos, Lucía; Torres, Marcelo Der Torossian; Blasco, Esther Broset; Oztekin, Sebahat; de la Fuente-Nunez, Cesar","year":2023,"journal":"Cell reports. Physical science, 4(7)","doi":"10.1016/j.xcrp.2023.101459","pmid":"38239869","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Lead synthetic peptides reduced bacterial loads by up to three orders of magnitude.","whyItMatters":"With rising antibiotic resistance, these new peptides could provide a crucial alternative for treating bacterial infections. Their effectiveness without promoting resistance is particularly significant.","specificNumbers":"","methodology":"The study involved structure-function-guided design, alanine scanning, and lysine substitutions to create and test 34 synthetic peptide derivatives.","limitations":"The study primarily involved in vitro tests and preclinical mouse models, which may not fully predict human responses."},{"rthcId":"RPEP-06748","title":"Thymosin beta-4 denotes new directions towards developing prosperous anti-aging regenerative therapies.","authors":"Bock-Marquette, Ildiko; Maar, Klaudia; Maar, Szabolcs; Lippai, Balint; Faskerti, Gabor; Gallyas, Ferenc; Olson, Eric N; Srivastava, Deepak","year":2023,"journal":"International immunopharmacology, 116, 109741","doi":"10.1016/j.intimp.2023.109741","pmid":"36709593","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Thymosin beta-4 demonstrated multiple regenerative effects in the heart:\n- In embryonic mice: TB4 is expressed in the developing heart and promotes cardiac cell migration and survival\n- After heart attack: systemic TB4 injections enhanced myocyte (heart muscle cell) survival and improved cardiac function following coronary artery ligation\n- In uninjured adults: intravenous TB4 altered adult epicardial morphology to resemble embryonic characteristics, increased cardiac vessel number, and shifted gene expression toward an embryonic profile\n- TB4 activated epicardial progenitor cells independent of hypoxic injury, suggesting regenerative effects don't require prior damage\n\nThe reactivation of an embryonic developmental program in adult tissue is the key conceptual advance — it suggests that developmentally relevant peptides could potentially reverse age-related cellular changes.","whyItMatters":"Heart disease is the leading cause of death worldwide, and the adult heart has very limited ability to regenerate after injury. TB4's ability to reactivate embryonic programs in the adult heart — including progenitor cell activation and new blood vessel formation — represents a fundamentally different approach to cardiac repair than current therapies. If this translates to humans, it could transform treatment of heart attacks, heart failure, and age-related cardiac decline.","specificNumbers":"","methodology":"The researchers combined developmental biology and cardiac injury studies. They analyzed TB4 expression during mouse embryonic heart development, then tested systemic (intravenous) TB4 injections in adult mice — both after acute myocardial infarction (coronary artery ligation) and in uninjured animals. Outcomes included cardiac function, cell survival, epicardial morphology, blood vessel formation, gene expression profiling, and progenitor cell activation.","limitations":"All findings are from mouse models, and the adult human heart differs significantly from the mouse heart in regenerative capacity and size. The review summarizes the authors' own research program, which may present selection bias in the evidence discussed. Long-term effects, optimal dosing, and potential risks (including uncontrolled cell proliferation) of systemic TB4 administration are not fully characterized. Clinical translation to humans remains to be demonstrated."},{"rthcId":"RPEP-06749","title":"Endogenous opiates and behavior: 2022.","authors":"Bodnar, Richard J","year":2023,"journal":"Peptides, 169, 171095","doi":"10.1016/j.peptides.2023.171095","pmid":"37704079","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review discusses multiple behavioral effects linked to opioid peptides and receptors across various contexts.","whyItMatters":"Understanding the role of endogenous opioids can inform treatment strategies for pain, addiction, and mental health disorders. This knowledge is crucial for developing better therapeutic approaches.","specificNumbers":"","methodology":"This is a review article summarizing findings from multiple studies published in 2022.","limitations":"As a review, it synthesizes existing research rather than presenting new experimental data, which may limit the depth of conclusions."},{"rthcId":"RPEP-06750","title":"Endogenous opiates and behavior: 2021.","authors":"Bodnar, Richard J","year":2023,"journal":"Peptides, 164, 171004","doi":"10.1016/j.peptides.2023.171004","pmid":"36990387","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"This review consolidates research from 2021 across 18 major topic areas related to endogenous opioid peptides: molecular/biochemical studies, animal and human pain/analgesia, nonopioid analgesics, tolerance and dependence, stress and social status, learning and memory, eating and drinking, drug abuse and alcohol, sexual activity and hormones, mental illness and mood, seizures, neurophysiology, locomotion, gastrointestinal/renal/hepatic function, cardiovascular responses, respiration and thermoregulation, and immunological responses.\n\nAs a comprehensive anthology, the review does not present a single finding but rather synthesizes the state of the field across all behavioral dimensions of opioid peptide research from a single year.","whyItMatters":"The endogenous opioid system is central to pain management, addiction, mood regulation, and numerous other physiological processes. This annual review series provides an invaluable consolidated reference that helps researchers track progress across the entire field and identify emerging trends in opioid peptide research.","specificNumbers":"","methodology":"This is a systematic annual review of published literature from 2021 covering all aspects of endogenous opioid peptide research. The author compiled and organized studies by topic area, covering molecular, pharmacological, and genetic manipulation of opioid peptides and receptors.","limitations":"As a review article, this does not present new experimental data. The quality and conclusions depend on the underlying studies reviewed, which vary in rigor. The breadth of coverage (18 topics) means individual studies receive limited detailed analysis. Only studies from 2021 are included."},{"rthcId":"RPEP-06751","title":"Agonist of growth hormone-releasing hormone improves the disease features of spinal muscular atrophy mice.","authors":"Boido, Marina; Gesmundo, Iacopo; Caretto, Anna; Pedrolli, Francesca; Schellino, Roberta; Leone, Sheila; Cai, Renzhi; Sha, Wei; Ghigo, Ezio; Schally, Andrew V; Vercelli, Alessandro; Granata, Riccarda","year":2023,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 120(2), e2216814120","doi":"10.1073/pnas.2216814120","pmid":"36603028","tags":["ghrh-agonist","growth-hormone"],"studyType":"animal-study","evidenceStrength":"moderate-preclinical","keyFinding":"Daily subcutaneous MR-409 treatment from postnatal day 2 to day 12 in SMNΔ7 SMA mice produced multiple beneficial effects, particularly at 2 mg/kg:\n\n- Increased body weight and improved motor behavior\n- Reduced muscle atrophy with increased fiber size in quadriceps and gastrocnemius\n- Upregulated myogenic genes and inhibited proteolytic (muscle-degrading) pathways\n- Promoted neuromuscular junction maturation (fewer multi-innervated endplates, more mono-innervated)\n- Delayed alpha motor neuron death in the spinal cord\n- Reduced neuroinflammation in the spinal cord\n\nThe breadth of effects — spanning muscle, nerve, and immune pathways — suggests GHRH agonists target multiple aspects of SMA pathology simultaneously.","whyItMatters":"Current SMA treatments focus on increasing SMN protein production through gene therapy or splice-modifying drugs. While revolutionary, these treatments don't fully correct the disease in all patients. GHRH agonists like MR-409 work through a completely different mechanism — protecting muscles and neurons independently of SMN levels. Combining GHRH agonists with existing SMN-targeted therapies could potentially achieve more complete disease control than either approach alone.","specificNumbers":"1 or 2 mg/kg MR-409 daily; P2-P12 treatment; increased body weight, fiber size, NMJ maturation; delayed motor neuron death; reduced neuroinflammation","methodology":"SMNΔ7 mice (established severe SMA model) received daily subcutaneous MR-409 at 1 or 2 mg/kg from postnatal day 2 to day 12. Outcomes included body weight, motor behavior testing, muscle histology (fiber size in quadriceps and gastrocnemius), gene expression analysis (myogenic and proteolytic pathways), neuromuscular junction maturation assessment (innervation patterns), spinal cord motor neuron counts, and neuroinflammation markers.","limitations":"Mouse model only; short 10-day treatment window; severe SMA model with short lifespan; no survival data in abstract; no comparison with current SMA therapies; long-term effects unknown."},{"rthcId":"RPEP-06752","title":"Primary weight loss failure after Roux-en-Y gastric bypass is characterized by impaired gut-hormone mediated regulation of food intake.","authors":"Bojsen-Møller, Kirstine Nyvold; Svane, Maria Saur; Martinussen, Christoffer; Dirksen, Carsten; Jørgensen, Nils Bruun; Jensen, Jens-Erik Beck; Jensen, Christian Zinck; Torekov, Signe Sørensen; Kristiansen, Viggo Bjerregaard; Rehfeld, Jens Frederik; Bork-Jensen, Jette; Grarup, Niels; Hansen, Torben; Hartmann, Bolette; Holst, Jens Juul; Madsbad, Sten","year":2023,"journal":"International journal of obesity (2005), 47(11), 1143-1151","doi":"10.1038/s41366-023-01372-8","pmid":"37653071","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Patients with primary weight loss failure had similar gut hormone levels but lower satiety scores compared to successful weight losers.","whyItMatters":"Understanding the hormonal responses in weight loss failure can help tailor treatments for patients struggling after gastric bypass surgery.","specificNumbers":"","methodology":"The study involved 20 women who received either octreotide or placebo, followed by meals to assess hormone levels and appetite responses.","limitations":"The study was limited to a small sample size of women, which may affect the generalizability of the findings."},{"rthcId":"RPEP-06753","title":"Late onset psychosis treatment with adjunctive medicines.","authors":"Boksha, Irina; Savushkina, Olga; Sheshenin, Vladimir; Tereshkina, Elena; Prokhorova, Tatyana; Pochueva, Valeriya; Burbaeva, Gulnur","year":2023,"journal":"Frontiers in psychiatry, 14, 1319891","doi":"10.3389/fpsyt.2023.1319891","pmid":"38188053","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06754","title":"Semaglutide in HFpEF across obesity class and by body weight reduction: a prespecified analysis of the STEP-HFpEF trial.","authors":"Borlaug, Barry A; Kitzman, Dalane W; Davies, Melanie J; Rasmussen, Søren; Barros, Eric; Butler, Javed; Einfeldt, Mette Nygaard; Hovingh, G Kees; Møller, Daniél Vega; Petrie, Mark C; Shah, Sanjiv J; Verma, Subodh; Abhayaratna, Walter; Ahmed, Fozia Z; Chopra, Vijay; Ezekowitz, Justin; Fu, Michael; Ito, Hiroshi; Lelonek, Małgorzata; Melenovsky, Vojtech; Núñez, Julio; Perna, Eduardo; Schou, Morten; Senni, Michele; van der Meer, Peter; Von Lewinski, Dirk; Wolf, Dennis; Kosiborod, Mikhail N","year":2023,"journal":"Nature medicine, 29(9), 2358-2365","doi":"10.1038/s41591-023-02526-x","pmid":"37635157","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide led to a 6.4-point improvement in KCCQ-CSS and a 14.4-meter improvement in 6MWD for each 10% body weight reduction.","whyItMatters":"These findings highlight the potential of semaglutide as a treatment option for improving heart failure symptoms in obese patients, which could enhance their quality of life.","specificNumbers":"","methodology":"This was a prespecified analysis of the STEP-HFpEF trial, focusing on dual primary and secondary endpoints across different obesity classes.","limitations":"The study's findings may not be generalizable to all heart failure patients, as it focused specifically on those with obesity phenotype."},{"rthcId":"RPEP-06755","title":"Dulaglutide and Kidney Function-Related Outcomes in Type 2 Diabetes: A REWIND Post Hoc Analysis.","authors":"Botros, Fady T; Gerstein, Hertzel C; Malik, Raleigh; Nicolay, Claudia; Hoover, Anastasia; Turfanda, Ibrahim; Colhoun, Helen M; Shaw, Jonathan E","year":2023,"journal":"Diabetes care, 46(8), 1524-1530","doi":"10.2337/dc23-0231","pmid":"37343574","tags":["glp-1-agonists","kidney-disease"],"studyType":"post-hoc-analysis","evidenceStrength":"strong","keyFinding":"Dulaglutide 1.5 mg reduced the risk of kidney function-related outcomes by 25% compared to placebo (HR 0.75, 95% CI 0.62–0.92, p = 0.004) in nearly 10,000 people with type 2 diabetes. Specifically, sustained ≥40% eGFR decline occurred 28% less frequently with dulaglutide (HR 0.72, p = 0.002).\n\nThe annual rate of kidney function decline was significantly slower with dulaglutide (-1.37 vs -1.56 mL/min/1.73 m²/year, p < 0.001). Importantly, the kidney-protective effect was consistent regardless of baseline kidney function or albumin levels — meaning it benefited patients across the spectrum of kidney health.","whyItMatters":"Diabetic kidney disease is the leading cause of kidney failure worldwide, affecting roughly 40% of people with type 2 diabetes. This analysis is significant because it strips out the albuminuria component — which was the main driver of the original REWIND kidney results — and shows that dulaglutide genuinely slows the loss of kidney function itself. This matters because eGFR decline is a harder, more clinically meaningful endpoint than albuminuria alone.","specificNumbers":"n=9,901 (4,949 dulaglutide, 4,952 placebo) · HR 0.75 (95% CI 0.62–0.92, p = 0.004) for composite kidney outcome · HR 0.72 (p = 0.002) for ≥40% sustained eGFR decline · eGFR slope: -1.37 vs -1.56 mL/min/1.73 m²/year (p < 0.001) · consistent across UACR and eGFR subgroups","methodology":"Post hoc analysis of the REWIND trial, a large randomized, placebo-controlled cardiovascular outcomes trial. Intent-to-treat analyses of 9,901 participants with type 2 diabetes examined kidney function endpoints (excluding macroalbuminuria) including sustained ≥40% eGFR decline, end-stage renal disease, and renal-related death. Subgroup analyses were conducted by baseline kidney function (eGFR) and albumin levels (UACR).","limitations":"Post hoc analysis — the kidney function outcomes were not the primary endpoint of the original REWIND trial, so these results are exploratory. The original trial was powered for cardiovascular events, not kidney endpoints. While the results are statistically significant and clinically meaningful, they require confirmation in a dedicated kidney outcomes trial. The subgroup analyses, while consistent, have limited statistical power individually."},{"rthcId":"RPEP-06756","title":"Identification of ACE I-Inhibitory Peptides Released by the Hydrolysis of Tub Gurnard (Chelidonichthys lucerna) Skin Proteins and the Impact of Their In Silico Gastrointestinal Digestion.","authors":"Bougatef, Hajer; de la Vega-Fernández, Cristina; Sila, Assaad; Bougatef, Ali; Martínez-Alvarez, Oscar","year":2023,"journal":"Marine drugs, 21(2)","doi":"10.3390/md21020131","pmid":"36827172","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Peptides from Esperase and Alcalase hydrolysates had IC50 values of 33 and 29 μg/mL, indicating strong ACE-inhibitory activity.","whyItMatters":"These findings could lead to new dietary sources for managing blood pressure, particularly from underutilized fish species. It highlights the potential of fish waste as a source of beneficial compounds.","specificNumbers":"","methodology":"The study involved hydrolyzing tub gurnard skin proteins using four different proteases and evaluating the resulting peptides for their ACE-inhibitory potential.","limitations":"The study primarily focuses on in vitro results, which may not fully translate to in vivo effects in humans."},{"rthcId":"RPEP-06757","title":"Improved Glycaemic and Weight Management Are Associated with Better Quality of Life in People with Type 2 Diabetes Treated with Tirzepatide.","authors":"Boye, Kristina S; Sapin, Hélène; Dong, Wenxiu; Williamson, Suzanne; Lee, Clare J; Thieu, Vivian Thuyanh","year":2023,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 14(11), 1867-1887","doi":"10.1007/s13300-023-01457-7","pmid":"37668888","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Lower HbA1c targets and higher weight loss percentages were linked to better quality of life ratings.","whyItMatters":"Improving quality of life for diabetes patients is crucial for their overall health and well-being. This study highlights the importance of achieving specific treatment targets.","specificNumbers":"","methodology":"The study pooled data from five Phase 3 clinical trials (SURPASS-1 to -5) assessing patient-reported outcomes related to HbA1c and weight loss in adults with type 2 diabetes.","limitations":"The study relies on pooled data from clinical trials, which may not fully represent real-world scenarios."},{"rthcId":"RPEP-06758","title":"The Real-World Observational Prospective Study of Health Outcomes with Dulaglutide and Liraglutide in Type 2 Diabetes Patients (TROPHIES): Final patient-reported outcomes at 24 months.","authors":"Boye, Kristina S; Lebrec, Jérémie; Dib, Anne; Heitmann, Elke; Federici, Marco Orsini; Yu, Maria; Sapin, Hélène; Barrett, Annabel; Guerci, Bruno; Giorgino, Francesco; Füchtenbusch, Martin; García-Pérez, Luis-Emilio","year":2023,"journal":"Diabetes, obesity & metabolism, 25(12), 3453-3464","doi":"10.1111/dom.15145","pmid":"37712754","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Patients on dulaglutide showed significantly better treatment satisfaction and self-perception related to weight compared to those on liraglutide.","whyItMatters":"Understanding patient experiences with diabetes treatments can guide healthcare providers in prescribing the most effective medications. Improved patient satisfaction may lead to better long-term adherence to treatment.","specificNumbers":"","methodology":"The TROPHIES study was a two-cohort, 24-month observational study conducted in France, Germany, and Italy, focusing on patient-reported outcomes in adults with type 2 diabetes starting injectable medications.","limitations":"The study was observational and conducted in specific countries, which may limit the generalizability of the findings."},{"rthcId":"RPEP-06759","title":"Neprilysin Inhibitors in Heart Failure: The Science, Mechanism of Action, Clinical Studies, and Unanswered Questions.","authors":"Bozkurt, Biykem; Nair, Ajith P; Misra, Arunima; Scott, Claire Z; Mahar, Jamal H; Fedson, Savitri","year":2023,"journal":"JACC. Basic to translational science, 8(1), 88-105","doi":"10.1016/j.jacbts.2022.05.010","pmid":"36777165","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"ARNi (angiotensin receptor-neprilysin inhibitor) therapy effectively reduces death and hospitalization in heart failure patients with NYHA functional class II-III symptoms. However, clinical trials failed to show benefits when compared to ACE inhibitors or ARBs in two populations: patients with advanced HF with reduced ejection fraction, and post-MI patients with left ventricular dysfunction but without HF. The review proposes that in advanced HF, downstream blunting of natriuretic peptide response limits efficacy, while post-MI patients without HF may not need increased natriuretic peptide availability.","whyItMatters":"Neprilysin inhibitors represented a major advance in heart failure treatment, but understanding their limitations is equally important. By clarifying which patients benefit (moderate HF) and which don't (advanced HF, post-MI without HF), this review helps clinicians make better prescribing decisions and highlights the importance of peptide biology in cardiovascular disease.","specificNumbers":"","methodology":"Contemporary review article analyzing recent clinical trial data on neprilysin inhibition in heart failure, examining mechanisms of action, and discussing unanswered questions about specific patient populations where the therapy may or may not be effective.","limitations":"This is a narrative review, not a systematic review or meta-analysis. The interpretations of why ARNi fails in certain populations are hypothetical and require further confirmation. Long-term effects of ARNi on albuminuria, obesity, glycemic control, lipid profile, blood pressure, and cognitive function remain understudied."},{"rthcId":"RPEP-06760","title":"Advances in Anti-obesity Pharmacotherapy: Current Treatments, Emerging Therapies, and Challenges.","authors":"Brandfon, Skyler; Eylon, Adi; Khanna, Deepesh; Parmar, Mayur S","year":2023,"journal":"Cureus, 15(10), e46623","doi":"10.7759/cureus.46623","pmid":"37937009","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review establishes two main categories of peptide-based anti-obesity therapies:\n\n1. GLP-1 receptor agonists work by stimulating satiety hormone secretion and are effective for obesity driven by excessive calorie intake. These are now among the most successful obesity treatments.\n\n2. Emerging genetic-targeted therapies address specific molecular defects: leptin analogs restore function in generalized lipodystrophy and related conditions, while melanocortin-4 receptor (MC4R) agonists target defects in the MC4R signaling pathway that regulates energy balance and appetite. These therapies fill a gap where conventional weight loss strategies fail — genetic obesity conditions like Bardet-Biedl syndrome and POMC deficiency.","whyItMatters":"Obesity affects over a third of US adults and is a leading cause of preventable death. While GLP-1 drugs have revolutionized treatment for common obesity, patients with genetic forms of obesity have had limited options. The emergence of targeted peptide therapies like leptin analogs (metreleptin) and MC4R agonists (setmelanotide) represents a shift toward precision medicine in obesity — matching the right drug to the right patient based on their underlying biology.","specificNumbers":"","methodology":"Comprehensive narrative review of anti-obesity medications covering clinical trial data, efficacy, FDA-approved indications, contraindications, and serious side effects. Drug classes reviewed include lipase inhibitors, GLP-1 receptor agonists, leptin analogs, and MC4R agonists.","limitations":"Published in Cureus (a community-driven journal), which may have less rigorous peer review than top-tier journals. The review may not capture the latest developments, particularly around tirzepatide and newer pipeline drugs. The coverage of emerging therapies is necessarily based on limited clinical trial data. Head-to-head comparisons between drug classes were not available for all agents discussed."},{"rthcId":"RPEP-06761","title":"Valorization of Chicken Slaughterhouse Byproducts to Obtain Antihypertensive Peptides.","authors":"Bravo, Francisca Isabel; Calvo, Enrique; López-Villalba, Rafael A; Torres-Fuentes, Cristina; Muguerza, Begoña; García-Ruiz, Almudena; Morales, Diego","year":2023,"journal":"Nutrients, 15(2)","doi":"10.3390/nu15020457","pmid":"36678328","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Multiple chicken slaughterhouse byproducts — including blood, bones, skins, and especially chicken feet — can be enzymatically broken down into protein hydrolysates containing peptides with ACE-inhibitory activity and blood pressure-lowering effects in animal models. The underlying mechanisms include increased endogenous antioxidant levels, reduced ACE activity, and improved endothelial dysfunction. However, clinical confirmation in humans is still lacking.","whyItMatters":"Hypertension is the leading preventable cause of cardiovascular death worldwide, and new approaches to managing it are needed. Food-derived bioactive peptides offer a natural, potentially low-cost alternative or complement to pharmaceutical ACE inhibitors. Using chicken slaughterhouse waste as a peptide source simultaneously addresses a health need and a sustainability challenge by turning low-value byproducts into functional ingredients.","specificNumbers":"","methodology":"Narrative review evaluating published research on the extraction and characterization of antihypertensive peptides from chicken slaughterhouse byproducts (blood, bones, skins, feet). The review assessed ACE-inhibitory activity data, blood pressure outcomes in animal models, and proposed mechanisms of action across the existing literature.","limitations":"The vast majority of cited studies used animal models (primarily spontaneously hypertensive rats), with very limited human clinical data. Bioavailability, dose-response relationships, and long-term safety of these peptides in humans remain uncharacterized. The enzymatic hydrolysis conditions vary widely across studies, making direct comparison of peptide potency difficult."},{"rthcId":"RPEP-06762","title":"Looking ahead to potential incretin combination therapies for nonalcoholic steatohepatitis in patients with diabetes.","authors":"Brodosi, Lucia; Petroni, Maria Letizia; Marchesini, Giulio","year":2023,"journal":"Expert opinion on pharmacotherapy, 24(9), 989-1000","doi":"10.1080/14656566.2023.2208746","pmid":"37114459","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Dual and triple agonists show effectiveness on NAFLD biomarkers, but most studies are ongoing.","whyItMatters":"With no approved treatments for NAFLD, these combination therapies could offer new hope for patients, especially those with diabetes. Understanding their effectiveness could lead to better management of liver disease.","specificNumbers":"","methodology":"The study involved a literature review of existing research on incretin combination therapies for NAFLD.","limitations":"Most studies reviewed are still in progress, and results may not yet be applicable to clinical practice."},{"rthcId":"RPEP-06763","title":"Defining the Intravital Renal Disposition of Fluorescence-Quenched Exenatide.","authors":"Bryniarski, Mark A; Sandoval, Ruben M; Ruszaj, Donna M; Fraser-McArthur, John; Yee, Benjamin M; Yacoub, Rabi; Chaves, Lee D; Campos-Bilderback, Silvia B; Molitoris, Bruce A; Morris, Marilyn E","year":2023,"journal":"Molecular pharmaceutics, 20(2), 987-996","doi":"10.1021/acs.molpharmaceut.2c00671","pmid":"36626167","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Exenatide was rapidly filtered by the kidneys, with metabolism occurring in the proximal tubule.","whyItMatters":"Understanding how exenatide is processed in the kidneys can improve the effectiveness of diabetes treatments and inform future drug development.","specificNumbers":"","methodology":"The study utilized Förster resonance energy transfer-quenched exenatide and intravital two-photon microscopy to observe kidney disposition in live rats.","limitations":"The study was conducted in rats, so results may not directly translate to humans."},{"rthcId":"RPEP-06764","title":"An IGFBP2-derived peptide promotes neuroplasticity and rescues deficits in a mouse model of Phelan-McDermid syndrome.","authors":"Burgdorf, Jeffrey S; Yoon, Sehyoun; Dos Santos, Marc; Lammert, Catherine R; Moskal, Joseph R; Penzes, Peter","year":2023,"journal":"Molecular psychiatry, 28(3), 1101-1111","doi":"10.1038/s41380-022-01904-0","pmid":"36481930","tags":["neuroprotective-peptides","autism-spectrum-disorder"],"studyType":"animal-study","evidenceStrength":"strong","keyFinding":"A synthetic peptide fragment called JB2, derived from insulin-like growth factor binding protein 2 (IGFBP2), rescued multiple deficits in a mouse model of Phelan-McDermid Syndrome (PMS) — a genetic form of autism. JB2 restored synaptic function and plasticity, improved learning and memory, normalized vocalizations and motor function, reduced seizure susceptibility, and corrected abnormal brainwave patterns (EEG measures) that are directly translatable to human testing.\n\nMechanistically, JB2 binds directly to synapses and dendrites, activating NMDA receptors and IGF2 receptors (but not IGF1 receptors) to trigger gene expression and extensive remodeling of the phosphoproteome. Among the affected proteins, autism risk factors and Shank3-associated networks were significantly enriched — suggesting JB2 directly targets the molecular pathways disrupted in PMS and broader ASD.","whyItMatters":"Phelan-McDermid Syndrome and many forms of autism have no approved treatments targeting the underlying biology — only symptom management. A peptide that rescues synaptic function, cognitive deficits, communication, motor problems, AND seizures in a genetic autism model is remarkable in its breadth. The fact that JB2 also normalized EEG biomarkers that can be measured in humans makes it especially promising for clinical translation.","specificNumbers":"JB2 peptide · IGFBP2-derived · rescued learning, memory, vocalizations, motor function · normalized EEG: auditory evoked response latency, alpha peak frequency, SSVEP · Shank3 heterozygous mouse model","methodology":"In vitro studies in cultured neurons and in vivo studies in Shank3 heterozygous mice (a model of Phelan-McDermid Syndrome). Assessed JB2's effects on synaptic structure, neuronal plasticity, phosphoproteome remodeling, behavior (learning, memory, vocalizations, motor function), neuronal excitability, seizure susceptibility, and electrophysiological biomarkers (EEG measures).","limitations":"Preclinical study in mice — results may not fully translate to human PMS or ASD. The Shank3 heterozygous mouse models one specific genetic cause of autism, so JB2 may not be effective across the full heterogeneous spectrum of ASD. Long-term safety, dosing, and blood-brain barrier penetration in humans are unknown. The gap between rescued mouse behaviors and meaningful clinical outcomes in human autism can be substantial."},{"rthcId":"RPEP-06765","title":"Semaglutide in Patients With Obesity and Heart Failure Across Mildly Reduced or Preserved Ejection Fraction.","authors":"Butler, Javed; Abildstrøm, Steen Z; Borlaug, Barry A; Davies, Melanie J; Kitzman, Dalane W; Petrie, Mark C; Shah, Sanjiv J; Verma, Subodh; Abhayaratna, Walter P; Chopra, Vijay; Ezekowitz, Justin A; Fu, Michael; Ito, Hiroshi; Lelonek, Małgorzata; Núñez, Julio; Perna, Eduardo; Schou, Morten; Senni, Michele; van der Meer, Peter; von Lewinski, Dirk; Wolf, Dennis; Altschul, Rebecca L; Rasmussen, Søren; Kosiborod, Mikhail N","year":2023,"journal":"Journal of the American College of Cardiology, 82(22), 2087-2096","doi":"10.1016/j.jacc.2023.09.811","pmid":"37993201","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"At 52 weeks, semaglutide improved symptoms and reduced body weight across all LVEF categories, with weight loss of -7.6 to -11.9 kg.","whyItMatters":"This research highlights the potential of semaglutide as a treatment option for a specific group of heart failure patients. It supports the use of this medication to improve quality of life in those with obesity and heart failure.","specificNumbers":"","methodology":"The study was a prespecified analysis of the STEP-HFpEF trial, which randomized 529 patients into semaglutide and placebo groups, assessing outcomes based on left ventricular ejection fraction (LVEF).","limitations":"The study's findings may not apply to all heart failure patients, and the long-term effects of semaglutide in this population are still unknown."},{"rthcId":"RPEP-06766","title":"Formulation and Evaluation of Insulin-Loaded Sodium-Alginate Microparticles for Oral Administration.","authors":"Bácskay, Ildikó; Papp, Boglárka; Pártos, Péter; Budai, István; Pető, Ágota; Fehér, Pálma; Ujhelyi, Zoltán; Kósa, Dóra","year":2023,"journal":"Pharmaceutics, 16(1)","doi":"10.3390/pharmaceutics16010046","pmid":"38258057","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The sodium-alginate microparticles achieved encapsulation efficiency above 80% across all formulations, meaning the vast majority of insulin was successfully trapped inside the beads. The pH-responsive alginate polymer protected insulin in acidic conditions (mimicking the stomach) and released it at higher pH (mimicking the intestine).\n\nAfter 120 minutes in simulated intestinal fluid containing digestive enzymes, 66% of the insulin remained intact — a meaningful improvement over unprotected insulin. Permeability testing using Caco-2 intestinal cell models showed that formulations containing the surfactant-based permeation enhancers (Labrasol ALF and Labrafil M 2125 CS at 0.10% v/v) significantly increased insulin transport across the cell layer compared to a control insulin solution.","whyItMatters":"Millions of people with diabetes inject insulin daily, which is painful, inconvenient, and reduces treatment adherence. An effective oral insulin formulation would be transformative for diabetes management. This study demonstrates a practical approach using safe, well-known materials (alginate, food-grade surfactants) that protect insulin through the stomach and enhance its absorption in the intestine.","specificNumbers":"","methodology":"Researchers formulated sodium-alginate microparticles loaded with insulin using an ionotropic gelation method. They incorporated two nonionic surfactant-based permeation enhancers (Labrasol ALF and Labrafil M 2125 CS) at 0.10% concentration, individually and in combinations. The microparticles were evaluated for encapsulation efficiency, in vitro drug release at different pH levels, enzymatic stability in simulated intestinal fluid (SIF), and permeability across Caco-2 cell monolayers (a standard model of the intestinal barrier).","limitations":"All testing was performed in vitro (in laboratory dishes), not in living animals or humans. Caco-2 cell models, while standard, are simplified representations of the intestinal wall and don't account for mucus layers, gut motility, or the full complexity of the GI tract. The 66% insulin survival after enzymatic exposure means a third of the insulin was still lost. No in vivo bioavailability or blood glucose-lowering data were reported."},{"rthcId":"RPEP-06767","title":"Oral vitamin D modulates the epidermal expression of the vitamin D receptor and cathelicidin in children with atopic dermatitis.","authors":"Cabalín, Carolina; Pérez-Mateluna, Guillermo; Iturriaga, Carolina; Camargo, Carlos A; Borzutzky, Arturo","year":2023,"journal":"Archives of dermatological research, 315(4), 761-770","doi":"10.1007/s00403-022-02416-1","pmid":"36273083","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Serum vitamin D levels increased from 45.1 to 93.5 nmoL/L, and AD severity decreased from 41.4 to 31.5 SCORAD.","whyItMatters":"This research highlights the potential of vitamin D as a simple intervention to improve skin health in children with eczema, which could lead to better management strategies.","specificNumbers":"","methodology":"An open-label study with 22 children receiving weekly oral vitamin D3 for six weeks, measuring skin and serum markers.","limitations":"The study had a small sample size and lacked a control group, which may affect the reliability of the findings."},{"rthcId":"RPEP-06768","title":"Enhanced lysosomal escape of cell penetrating peptide-functionalized metal-organic frameworks for co-delivery of survivin siRNA and oridonin.","authors":"Cai, Mengru; Yao, Yu; Yin, Dongge; Zhu, Rongyue; Fu, Tingting; Kong, Jiahui; Wang, Kaixin; Liu, Jing; Yao, Aina; Ruan, Yidan; Shi, Wenjuan; Zhu, Qian; Ni, Jian; Yin, Xingbin","year":2023,"journal":"Journal of colloid and interface science, 646, 370-380","doi":"10.1016/j.jcis.2023.04.126","pmid":"37207419","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The co-delivery system improved anti-tumor effects significantly, demonstrating a synergistic effect.","whyItMatters":"This research highlights a promising strategy for improving cancer therapies by combining gene therapy with traditional treatments, potentially leading to better patient outcomes.","specificNumbers":"","methodology":"The study involved designing a metal-organic framework nanoplatform modified with cell-penetrating peptides to enhance drug delivery in vitro and in vivo.","limitations":"The study does not specify the exact sample sizes or the long-term effects of the treatment."},{"rthcId":"RPEP-06769","title":"Identification of a short ACE2-derived stapled peptide targeting the SARS-CoV-2 spike protein.","authors":"Calugi, Lorenzo; Sautariello, Giulia; Lenci, Elena; Mattei, Mauro Leucio; Coppa, Crescenzo; Cini, Nicoletta; Contini, Alessandro; Trabocchi, Andrea","year":2023,"journal":"European journal of medicinal chemistry, 249, 115118","doi":"10.1016/j.ejmech.2023.115118","pmid":"36682293","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A 9-amino-acid peptide (sequence HEAEDLFYQ, residues 34–42 of ACE2 α-helix 1) was chemically stapled using ring-closing metathesis at the i to i+4 positions. This stapled peptide competed with recombinant ACE2 for binding to the SARS-CoV-2 Spike receptor-binding domain (RBD) at micromolar concentrations in a colorimetric ELISA assay.\n\nCircular dichroism studies confirmed the ring-closing metathesis staple stabilized the helical structure more effectively than an alternative triazole staple produced by click chemistry. Molecular dynamics simulations further showed the stapled peptide not only bound the Spike RBD and sterically interfered with ACE2 binding, but displayed higher affinity for the target than the unstapled parent epitope.","whyItMatters":"Most COVID-19 treatments target the virus after it has already entered cells. A peptide that blocks the spike protein from grabbing ACE2 could stop infection at the very first step — viral entry. Because the peptide is small (only 9 amino acids), it could be easier to manufacture and potentially deliver as an inhaled or nasal treatment, offering an alternative to large antibody-based therapies.","specificNumbers":"","methodology":"The researchers synthesized a series of peptide derivatives based on a short segment of the ACE2 receptor's first alpha-helix. They used two different chemical stapling approaches — ring-closing metathesis and click chemistry (triazole) — to lock the peptides into their helical shape. Binding to the SARS-CoV-2 spike protein was tested using a colorimetric ELISA screening assay, and the peptides' structures were analyzed with circular dichroism spectroscopy. Molecular dynamics (MD) simulations were run to model how the stapled peptide interacts with the spike protein's receptor-binding domain.","limitations":"All experiments were conducted in vitro using purified proteins and computer simulations — no cell-based infection assays or animal studies were reported. The binding affinity was in the micromolar range, which is relatively modest compared to therapeutic antibodies. The peptide's stability in biological fluids, its ability to reach target tissues, and any potential off-target effects remain unknown. Results with isolated spike RBD may not fully reflect the behavior of the trimeric spike on intact virus particles."},{"rthcId":"RPEP-06770","title":"Efficacy and Safety of Erenumab, Galcanezumab, and Fremanezumab in the Treatment of Drug-Resistant Chronic Migraine: Experience in Real Clinical Practice.","authors":"Cantarelli, Lorenzo; Pestana Grafiña, Diana; Gonzalez Perez, Amanda; García Gil, Sara; Gutiérrez Nicolás, Fernando; Ramos Santana, Emma; Navarro Dávila, Marco Antonio; Otazo Pérez, Sheila María; Calzado Gómez, Gloria; Perez Reyes, Sergio; Nazco Casariego, Gloria Julia","year":2023,"journal":"The Annals of pharmacotherapy, 57(4), 416-424","doi":"10.1177/10600280221118402","pmid":"35979920","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Patients experienced a reduction in migraine headache days and improved scores on disability and headache impact scales at 12 and 24 weeks.","whyItMatters":"Understanding the real-world effectiveness and safety of these treatments can help guide clinical decisions for chronic migraine patients. It highlights the importance of dose optimization in treatment plans.","specificNumbers":"","methodology":"This was a single-center, retrospective study analyzing patient data from 2019 to 2022.","limitations":"The study was limited to a single center and retrospective in nature, which may affect the generalizability of the findings."},{"rthcId":"RPEP-06771","title":"Glucagon-like peptide 1 receptor agonists and the potential risk of pancreatic carcinoma: a pharmacovigilance study using the FDA Adverse Event Reporting System and literature visualization analysis.","authors":"Cao, Mingnan; Pan, Chen; Tian, Yue; Wang, Li; Zhao, Zhigang; Zhu, Bin","year":2023,"journal":"International journal of clinical pharmacy, 45(3), 689-697","doi":"10.1007/s11096-023-01556-2","pmid":"36977858","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"3073 pancreatic carcinoma cases were reported related to GLP-1RAs, with liraglutide showing the strongest association (ROR 54.45).","whyItMatters":"Understanding the potential risks associated with GLP-1RAs is crucial for patient safety and informed decision-making in diabetes treatment. This study highlights the need for careful monitoring of these medications.","specificNumbers":"","methodology":"The study used disproportionality and Bayesian analyses for signal detection, including reporting odds ratio (ROR) and proportional reporting ratio (PRR), along with a keyword co-occurrence analysis.","limitations":"The study relies on reported cases, which may not capture all instances of pancreatic cancer, and causality cannot be definitively established."},{"rthcId":"RPEP-06772","title":"Antifungal activity of a shortened analogue of the natural peptide LyeTx I isolated from the venom of the spider Lycosa erythrognatha.","authors":"Cardoso, Bárbara Gatti; de Lima, William Gustavo; Fernandes, Simone Odília Antunes; de Lima, Maria Elena; Cardoso, Valbert Nascimento","year":2023,"journal":"Natural product research, 37(5), 759-763","doi":"10.1080/14786419.2022.2079122","pmid":"35731024","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"LyeTx I mnΔK demonstrated MIC and MFC values between 4 and 32 µM and inhibited biofilm formation by 67% at 32 µM.","whyItMatters":"With rising fungal infections and resistance to current treatments, new antifungal agents like LyeTx I mnΔK are crucial for public health. This peptide could lead to effective therapies against resistant fungal strains.","specificNumbers":"","methodology":"The study evaluated the antifungal activity of LyeTx I mnΔK against various Candida species, measuring MIC, MFC, and biofilm disruption.","limitations":"The study primarily focuses on in vitro results, and further research is needed to assess efficacy in vivo and in clinical settings."},{"rthcId":"RPEP-06773","title":"Holistic profiling of the venom from the Brazilian wandering spider Phoneutria nigriventer by combining high-throughput ion channel screens with venomics.","authors":"Cardoso, F C; Walker, A A; King, G F; Gomez, M V","year":2023,"journal":"Frontiers in molecular biosciences, 10, 1069764","doi":"10.3389/fmolb.2023.1069764","pmid":"36865382","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Identified 27 novel cysteine-rich venom peptides with unknown activity.","whyItMatters":"Understanding spider venom can lead to new therapeutic agents for various diseases. This research highlights the potential of venom-derived peptides in pharmacology.","specificNumbers":"","methodology":"The study combined high-throughput cellular assays with proteomics to analyze the venom's effects on ion channels.","limitations":"The study primarily focuses on in vitro findings, which may not fully translate to in vivo effects in humans."},{"rthcId":"RPEP-06774","title":"Topoisomeric Membrane-Active Peptides: A Review of the Last Two Decades.","authors":"Carrera-Aubesart, Adam; Gallo, Maria; Defaus, Sira; Todorovski, Toni; Andreu, David","year":2023,"journal":"Pharmaceutics, 15(10)","doi":"10.3390/pharmaceutics15102451","pmid":"37896211","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Topoisomeric peptides can maintain biological activity while resisting protease degradation.","whyItMatters":"Understanding how these peptides interact with cell membranes could lead to new therapeutic strategies in drug delivery and infection control. Their stability against degradation enhances their potential for clinical applications.","specificNumbers":"","methodology":"The study is a review that synthesizes findings from the last two decades on membrane-active peptides.","limitations":"As a review, it does not present original experimental data and may not cover all recent studies comprehensively."},{"rthcId":"RPEP-06775","title":"Effect of semaglutide on fatty liver disease biomarkers in patients with diabetes and obesity.","authors":"Carretero-Gómez, Juana; Carrasco-Sánchez, Francisco Javier; Fernández-Rodríguez, José María; Casado-Escribano, Pedro; Miramontes-González, José Pablo; Seguí-Ripoll, José Miguel; Ena, Javier; Arévalo-Lorido, José Carlos","year":2023,"journal":"Revista clinica espanola, 223(3), 134-143","doi":"10.1016/j.rceng.2022.12.001","pmid":"36549643","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"At 24 weeks, semaglutide reduced the hepatic steatosis index (HSI) by 2.36 and the fibrosis-4 index (FIB-4) by 0.075.","whyItMatters":"Improving liver health in diabetic patients can reduce the risk of severe liver disease. This study highlights semaglutide's potential benefits beyond blood sugar control.","specificNumbers":"","methodology":"The study was a multicenter, prospective, pre-post, uncontrolled cohort analysis involving patients with type 2 diabetes treated with semaglutide.","limitations":"The study was uncontrolled and lacked a comparison group, which may affect the reliability of the findings."},{"rthcId":"RPEP-06776","title":"Glucometabolic outcomes of GLP-1 receptor agonist-based therapies in patients with type 2 diabetes: a systematic review and network meta-analysis.","authors":"Caruso, Irene; Di Gioia, Ludovico; Di Molfetta, Sergio; Cignarelli, Angelo; Palmer, Suetonia Cressida; Natale, Patrizia; Strippoli, Giovanni F M; Perrini, Sebastio; Natalicchio, Annalisa; Laviola, Luigi; Giorgino, Francesco","year":2023,"journal":"EClinicalMedicine, 64, 102181","doi":"10.1016/j.eclinm.2023.102181","pmid":"37719418","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tirzepatide 15 mg reduced HbA1c by 0.40% more than iDegLira and 0.48% more than iGlarLixi, without increasing hypoglycemia risk.","whyItMatters":"Understanding the effectiveness of different diabetes treatments can help healthcare providers make informed decisions, ultimately improving patient outcomes. This research highlights the potential of tirzepatide as a leading option.","specificNumbers":"","methodology":"The study conducted a network meta-analysis of 40 randomized controlled trials comparing different GLP-1 receptor agonist treatments.","limitations":"The study relies on existing trials, which may vary in quality and design, and it does not include long-term outcomes."},{"rthcId":"RPEP-06777","title":"Physiological and pharmacological overview of the gonadotropin releasing hormone.","authors":"Casati, Lavinia; Ciceri, Samuele; Maggi, Roberto; Bottai, Daniele","year":2023,"journal":"Biochemical pharmacology, 212, 115553","doi":"10.1016/j.bcp.2023.115553","pmid":"37075816","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GnRH is involved in reproductive functions and has roles in tumor growth and neurogenesis.","whyItMatters":"Understanding GnRH's functions can enhance treatments for infertility and possibly other health conditions. Its broader implications in neurogenesis and tumor biology make it a significant area of research.","specificNumbers":"","methodology":"This is a review article summarizing existing research on GnRH and its pharmacological applications.","limitations":"As a review, it synthesizes existing literature rather than presenting new experimental data."},{"rthcId":"RPEP-06778","title":"Rapid Evaluation of Staple Placement in Stabilized α Helices Using Bacterial Surface Display.","authors":"Case, Marshall; Navaratna, Tejas; Vinh, Jordan; Thurber, Greg","year":2023,"journal":"ACS chemical biology, 18(4), 905-914","doi":"10.1021/acschembio.3c00048","pmid":"37039514","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Identified several novel peptide antagonists with nanomolar and sub-nanomolar affinities.","whyItMatters":"This research could lead to the development of more effective therapies for diseases involving hard-to-reach proteins. It enhances our understanding of peptide design for better drug development.","specificNumbers":"","methodology":"The study employed stabilized peptide engineering by Escherichia coli display (SPEED) to screen various staple locations and chemistries.","limitations":"The study primarily focuses on in vitro evaluations, which may not fully translate to in vivo effectiveness in humans."},{"rthcId":"RPEP-06779","title":"Glucagon-like peptide 1(GLP-1) receptor agonists in the management of the patient with type 2diabetes mellitus and chronic kidney disease: an approach for the nephrologist.","authors":"Cases, Aleix","year":2023,"journal":"Nefrologia, 43(4), 399-412","doi":"10.1016/j.nefroe.2023.09.003","pmid":"37813741","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 receptor agonists offer cardiovascular and renal benefits with a low risk of hypoglycemia.","whyItMatters":"This research highlights a promising treatment option for patients with type 2 diabetes and CKD, addressing significant health risks. It could lead to better management strategies and improved patient outcomes.","specificNumbers":"","methodology":"This is a review study analyzing the effects of GLP-1 receptor agonists on cardiovascular and renal health in diabetic patients.","limitations":"The review focuses on existing literature and may not include all recent studies or clinical trials."},{"rthcId":"RPEP-06780","title":"The evolution of antimicrobial peptides in Chiroptera.","authors":"Castellanos, Francisco X; Moreno-Santillán, Diana; Hughes, Graham M; Paulat, Nicole S; Sipperly, Nicolette; Brown, Alexis M; Martin, Katherine R; Poterewicz, Gregory M; Lim, Marisa C W; Russell, Amy L; Moore, Marianne S; Johnson, Matthew G; Corthals, Angelique P; Ray, David A; Dávalos, Liliana M","year":2023,"journal":"Frontiers in immunology, 14, 1250229","doi":"10.3389/fimmu.2023.1250229","pmid":"37822944","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Identified 29 AMP families, with α-, β-defensins, and cathelicidins making up about 10% of AMP diversity.","whyItMatters":"Understanding the evolution of AMPs in bats can provide insights into immune responses that may be applicable to other species, including humans. This research highlights the need for more detailed studies on non-model organisms.","specificNumbers":"","methodology":"The study employed a bioinformatic pipeline to analyze AMP gene families in various bat species.","limitations":"The study primarily relies on bioinformatics and may not capture all functional aspects of AMPs in vivo."},{"rthcId":"RPEP-06781","title":"Mechanism of preventive effects of exendin-4 and des-fluoro-sitagliptin in a murine model of fructose-induced prediabetes.","authors":"Castro, María Cecilia; Villagarcía, Hernán Gonzalo; Schinella, Guillermo; Massa, María Laura; Francini, Flavio","year":2023,"journal":"Biochimica et biophysica acta. Molecular and cell biology of lipids, 1868(9), 159363","doi":"10.1016/j.bbalip.2023.159363","pmid":"37429413","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Both exendin-4 and des-fluoro-sitagliptin prevented hypertriglyceridemia and oxidative stress in fructose-fed rats.","whyItMatters":"These findings highlight potential therapeutic strategies for preventing liver damage associated with high sugar diets, which is increasingly relevant given rising obesity rates.","specificNumbers":"","methodology":"The study involved a 21-day fructose-rich diet in rats, measuring various metabolic and liver function markers, alongside in vitro tests on HepG2 cells.","limitations":"The study was conducted in rats, and results may not directly translate to humans. The long-term effects and safety of these treatments were not assessed."},{"rthcId":"RPEP-06782","title":"Recent Advances in Urinary Peptide and Proteomic Biomarkers in Chronic Kidney Disease: A Systematic Review.","authors":"Catanese, Lorenzo; Siwy, Justyna; Mischak, Harald; Wendt, Ralph; Beige, Joachim; Rupprecht, Harald","year":2023,"journal":"International journal of molecular sciences, 24(11)","doi":"10.3390/ijms24119156","pmid":"37298105","tags":["peptide-biomarkers"],"studyType":"systematic-review","evidenceStrength":"high","keyFinding":"From a systematic search of 3,668 articles, 62 studies met inclusion criteria and identified eight established single peptide biomarkers plus several proteomic classifiers (including CKD273 and IgAN237) for chronic kidney disease. These urinary peptide biomarkers show potential to detect kidney disease earlier than the current standard tests — serum creatinine and urinary albumin — which have known blind spots in early-stage kidney impairment.\n\nProteomic classifiers that analyze patterns across hundreds of peptides simultaneously (like CKD273, which uses 273 urinary peptides) are emerging as the most promising approach for clinical implementation.","whyItMatters":"Chronic kidney disease affects hundreds of millions of people worldwide, and current diagnostic tests miss early-stage disease when intervention would be most effective. Urinary peptide biomarkers could detect kidney damage before irreversible loss of function occurs. This systematic review maps the landscape of what's available and what's closest to clinical use, providing a roadmap for the transition from creatinine-based diagnostics to precision peptide-based detection.","specificNumbers":"3,668 articles screened · 62 studies included · 8 single peptide biomarkers · CKD273 (273-peptide classifier) · IgAN237 (237-peptide classifier) · 5-year literature window","methodology":"PRISMA-compliant systematic review searching the Web of Science database (October 2022) for English-language, full-text, original human studies published within the last 5 years and cited at least 5 times per year. Three independent authors performed abstract and full-text analysis. Excluded: animal models, transplant studies, metabolite/miRNA/exosomal vesicle studies.","limitations":"Limited to the Web of Science database, potentially missing studies indexed only in other databases. The 5-times-per-year citation requirement may exclude newer but important studies. The field is rapidly evolving, and the October 2022 search cutoff means more recent discoveries are not captured. Clinical validation and regulatory approval for most biomarkers discussed remain incomplete."},{"rthcId":"RPEP-06783","title":"Immunity elicited by AMP-encoding plasmids fails to increase the protection of European sea bass against nodavirus.","authors":"Cervera, Laura; González-Fernández, Carmen; Cano, Daniela; Esteban, M Ángeles; Mercado, Luis; Chaves-Pozo, Elena; Cuesta, Alberto","year":2023,"journal":"Fish & shellfish immunology, 132, 108507","doi":"10.1016/j.fsi.2022.108507","pmid":"36581252","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"AMP-encoding plasmids increased fish mortality from nodavirus despite enhancing immune response.","whyItMatters":"Understanding the immune response in sea bass can help improve aquaculture practices. However, the negative impact of AMP plasmids on nodavirus resistance raises concerns about their use.","specificNumbers":"","methodology":"The study involved injecting sea bass juveniles with plasmids encoding various AMPs and assessing immune responses and mortality rates.","limitations":"The study focused only on specific AMPs and their effects on nodavirus, which may not represent all possible outcomes."},{"rthcId":"RPEP-06784","title":"Temperature-Induced Nanostructure Transition for Supramolecular Gelation in Water.","authors":"Chakravarthy, Rajan Deepan; Sahroni, Imam; Wang, Chen-Wen; Mohammed, Mohiuddin; Lin, Hsin-Chieh","year":2023,"journal":"ACS nano, 17(12), 11805-11816","doi":"10.1021/acsnano.3c02753","pmid":"37294326","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The gel's stiffness increased approximately 14-fold from 20 to 37 °C.","whyItMatters":"This advancement could significantly improve the use of hydrogels in biomedical applications, especially in tissue engineering, by providing both injectability and enhanced mechanical properties.","specificNumbers":"","methodology":"The researchers developed a temperature-induced nanostructure transition system to create supramolecular hydrogels through the co-assembly of peptides and PEG.","limitations":"The study primarily focuses on in vitro results, and further research is needed to confirm efficacy in vivo."},{"rthcId":"RPEP-06785","title":"Characteristics and Absorption Rate of Whey Protein Hydrolysates Prepared Using Flavourzyme after Treatment with Alcalase and Protamex.","authors":"Chang, Yeok Boo; Kim, Hyeongyeong; Lee, Se Kyung; Kim, Hye-Jin; Jeong, A-Hyun; Suh, Hyung Joo; Ahn, Yejin","year":2023,"journal":"Molecules (Basel, Switzerland), 28(24)","doi":"10.3390/molecules28247969","pmid":"38138458","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"LMWPH showed a faster absorption rate, increasing serum protein content at 20 minutes compared to 40 minutes for WPC.","whyItMatters":"Understanding the absorption characteristics of whey protein hydrolysates can help in developing more effective protein supplements and functional foods.","specificNumbers":"","methodology":"The study utilized molecular weight distribution analysis and Fourier-transform infrared spectroscopy to evaluate the properties of whey protein hydrolysates.","limitations":"The study did not explore long-term effects or the impact of these findings on different populations."},{"rthcId":"RPEP-06786","title":"Persistence to anti-CGRP monoclonal antibodies and onabotulinumtoxinA among patients with migraine: a retrospective cohort study.","authors":"Charleston, Larry; Talon, Brian; Sullivan, Christine; Anderson, Carlton; Kymes, Steven; Regnier, Stephane A; Soni-Brahmbhatt, Seema; Nahas, Stephanie J","year":2023,"journal":"The journal of headache and pain, 24(1), 101","doi":"10.1186/s10194-023-01636-8","pmid":"37532991","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Eptinezumab-treated patients had a significantly lower discontinuation hazard compared to those on other anti-CGRP mAbs, with 32% to 58% higher hazards for other treatments.","whyItMatters":"Understanding treatment persistence is crucial for managing migraines effectively. This study highlights the potential advantages of eptinezumab, which could influence treatment choices for patients and healthcare providers.","specificNumbers":"","methodology":"The study used a retrospective cohort design, analyzing data from 66,576 patients treated with either anti-CGRP mAbs or onabotulinumtoxinA over a specified period.","limitations":"The study is retrospective and may be subject to biases in data collection and interpretation. It also does not account for all possible confounding factors influencing treatment persistence."},{"rthcId":"RPEP-06787","title":"Cyclobutane-bearing restricted anchoring residues enabled geometry-specific hydrocarbon peptide stapling.","authors":"Chen, Baobao; Liu, Chao; Cong, Wei; Gao, Fei; Zou, Yan; Su, Li; Liu, Lei; Hillisch, Alexander; Lehmann, Lutz; Bierer, Donald; Li, Xiang; Hu, Hong-Gang","year":2023,"journal":"Chemical science, 14(41), 11499-11506","doi":"10.1039/d3sc04279k","pmid":"37886087","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"E7-E7 geometry-specific stapled peptides exhibited higher α-helicity and stronger biological activity than traditional hydrocarbon stapled peptides.","whyItMatters":"This research could lead to more effective peptide therapeutics, particularly in combating viral infections like COVID-19. The findings may also inspire new strategies in peptide design.","specificNumbers":"","methodology":"The study involved the rational design and synthesis of cyclobutane-based amino acids, followed by ring-closing metathesis to create stapled peptides.","limitations":"The study primarily focuses on synthetic peptides, and further research is needed to assess their effectiveness in vivo."},{"rthcId":"RPEP-06788","title":"Unleashing the potential of natural biological peptide Macropin: Hydrocarbon stapling for effective breast cancer treatment.","authors":"Chen, Baobao; Li, Yinghua; Bai, Haohao; Ji, Yajing; Cong, Wei; Hu, Honggang; He, Shipeng","year":2023,"journal":"Bioorganic chemistry, 140, 106770","doi":"10.1016/j.bioorg.2023.106770","pmid":"37604094","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among the panel of stapled Macropin-1 variants synthesized, Mac-1-sp4 demonstrated the most comprehensive improvements: enhanced α-helical structure, greater resistance to protease degradation, improved cell membrane permeability, stronger induction of cancer cell apoptosis, in vivo antitumor activity against breast cancer, and inhibition of tubulin polymerization — the protein assembly process required for cell division.\n\nThe hydrocarbon stapling modification successfully addressed the two main limitations of the natural linear peptide: its inability to efficiently cross cell membranes and its vulnerability to enzymatic breakdown.","whyItMatters":"Natural peptides from animal venoms have long been recognized as potent bioactive molecules, but their clinical use has been limited by poor stability and cell penetration. Hydrocarbon stapling is emerging as a powerful tool to transform these molecules into viable drug candidates. This study provides a clear example of how a single chemical modification strategy can simultaneously solve multiple drug development challenges for a venom-derived peptide targeting breast cancer.","specificNumbers":"","methodology":"The researchers used hydrocarbon stapling — a chemical technique that locks peptides into their active helical shape using hydrocarbon cross-links — to create multiple modified versions of bee venom peptide Macropin-1. Each variant was evaluated for secondary structure (helicity), stability against proteolytic enzymes, cell membrane permeability, ability to induce apoptosis in breast cancer cells, tubulin polymerization inhibition, and in vivo antitumor activity in animal models.","limitations":"The study used in vitro cell models and animal tumor models, which may not fully predict efficacy in human breast cancer patients. Specific quantitative results (tumor size reduction, IC50 values, survival data) were not detailed in the abstract. Off-target toxicity and therapeutic window in vivo were not thoroughly characterized. The study focused on breast cancer only, so activity against other cancer types is unknown."},{"rthcId":"RPEP-06789","title":"Comparative efficacy and safety of glucagon-like peptide 1 receptor agonists for the treatment of type 2 diabetes: A network meta-analysis.","authors":"Chen, Han; Li, Xin-Zhu; Chen, Jia-Qing; Ren, Tian-Shu; Zhang, Ying-Shi; Wang, Yi-Nuo; Zhao, Qing-Chun","year":2023,"journal":"Medicine, 102(27), e34122","doi":"10.1097/MD.0000000000034122","pmid":"37417602","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The network meta-analysis of 12 RCTs covering 6,213 patients and 10 GLP-1RA regimens produced a clear efficacy ranking for HbA1c reduction: Semaglutide 2.0mg > Semaglutide 1.0mg > Dulaglutide 4.5mg > Semaglutide 0.5mg > Dulaglutide 3.0mg > PEX168 200μg > Dulaglutide 1.5mg > PEX168 100μg > Dulaglutide 0.75mg. All once-weekly GLP-1RAs were significantly better than placebo.\n\nSafety analysis showed comparable hypoglycemia risk across all regimens, and all long-acting GLP-1RAs (except PEX168) had lower rates of diarrhea, nausea, and vomiting than placebo.","whyItMatters":"With multiple GLP-1 receptor agonist peptide drugs available, clinicians need evidence to guide treatment selection. This analysis provides a direct comparison of options that have rarely been tested head-to-head, helping physicians choose the most effective regimen for their patients while understanding the safety trade-offs.","specificNumbers":"","methodology":"Systematic review and network meta-analysis of randomized controlled trials from PubMed, EMBASE, and Cochrane Library (searched through June 2022). Included RCTs enrolled type 2 diabetes patients with at least 12 weeks follow-up comparing four weekly GLP-1RAs against each other or placebo. Frequentist random-effect network meta-analysis was used. Registered on PROSPERO (CRD42022342241).","limitations":"The minimum 12-week follow-up may miss longer-term efficacy differences and rare adverse events. The analysis focused on glycemic outcomes and did not compare weight loss, cardiovascular outcomes, or kidney effects. Some comparisons in the network may have been informed by few studies. Exenatide once-weekly was not included in the final ranking despite being listed. PEX168 (loxenatide) is primarily available in China, limiting generalizability."},{"rthcId":"RPEP-06790","title":"The role of C-peptide in diabetes and its complications: an updated review.","authors":"Chen, Jintao; Huang, Yajing; Liu, Chuanfeng; Chi, Jingwei; Wang, Yangang; Xu, Lili","year":2023,"journal":"Frontiers in endocrinology, 14, 1256093","doi":"10.3389/fendo.2023.1256093","pmid":"37745697","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06791","title":"The effect of oral supplements containing collagen peptides rich in X-Hyp or X-Hyp-Gly compared with normal collagen hydrolysates on skin elasticity and collagen holes: a randomised double-blind clinical study.","authors":"Chen, Ling; Lv, Yuan; Xu, Feifei; Zhong, Fang","year":2023,"journal":"Food & function, 14(23), 10628-10638","doi":"10.1039/d3fo02873a","pmid":"37970760","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Skin elasticity increased from R2 values of 0.86 to 0.92 in the intervention group (P < 0.05).","whyItMatters":"Improving skin elasticity can enhance skin health and appearance, making these supplements potentially valuable in skincare. This research supports the use of specific collagen peptides in dietary supplements.","specificNumbers":"","methodology":"A double-blind, randomized clinical trial with 30 participants aged 22-30, comparing collagen peptides with normal hydrolysates over 42 days.","limitations":"The study had a small sample size of 30 participants, which may limit the generalizability of the findings."},{"rthcId":"RPEP-06792","title":"Alternative role of glucagon-like Peptide-1 receptor agonists in neurodegenerative diseases.","authors":"Chen, Shang-Der; Chuang, Yao-Chung; Lin, Tsu-Kung; Yang, Jenq-Lin","year":2023,"journal":"European journal of pharmacology, 938, 175439","doi":"10.1016/j.ejphar.2022.175439","pmid":"36470445","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1R agonists may reduce neuroinflammation and promote neurogenesis in neurodegenerative diseases.","whyItMatters":"With limited treatment options for neurodegenerative diseases, repurposing GLP-1R agonists could provide new therapeutic avenues. This could significantly impact patient care and reduce the societal burden of these conditions.","specificNumbers":"","methodology":"The study is a review of recent preclinical and clinical research on GLP-1R agonists in neurodegenerative diseases.","limitations":"The review primarily summarizes existing studies without presenting new experimental data, limiting direct evidence of efficacy."},{"rthcId":"RPEP-06793","title":"Cation-π Interaction Trigger Supramolecular Hydrogelation of Peptide Amphiphiles.","authors":"Chen, Shuang; Li, Zenghui; Zhang, Chunhui; Wu, Xia; Wang, Wenjie; Huang, Qingjun; Chen, Weiyu; Shi, Junfeng; Yuan, Dan","year":2023,"journal":"Small (Weinheim an der Bergstrasse, Germany), 19(25), e2301063","doi":"10.1002/smll.202301063","pmid":"36932893","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Cation-π interactions serve as a major driving force for peptide folding and hydrogel formation.","whyItMatters":"This research provides a novel approach to creating biomaterials, which could have applications in drug delivery and tissue engineering.","specificNumbers":"","methodology":"The study involved designing peptide amphiphiles and investigating their self-assembly into hydrogels through both computational and experimental methods.","limitations":"The study primarily focuses on in vitro conditions, which may not fully represent in vivo environments."},{"rthcId":"RPEP-06794","title":"Stabilized cyclic peptides as modulators of protein-protein interactions: promising strategies and biological evaluation.","authors":"Cheng, Jiongjia; Zhou, Junlong; Kong, Lingyan; Wang, Haiying; Zhang, Yuchi; Wang, Xiaofeng; Liu, Guangxiang; Chu, Qian","year":2023,"journal":"RSC medicinal chemistry, 14(12), 2496-2508","doi":"10.1039/d3md00487b","pmid":"38107173","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Cyclic peptides have improved stability and bioavailability, making them viable PPI modulators.","whyItMatters":"Targeting protein-protein interactions is crucial for developing new therapies for diseases, and cyclic peptides offer a promising approach to overcome challenges in this area.","specificNumbers":"","methodology":"The study is a comprehensive review of recent advancements in cyclic peptide design and their applications in modulating PPIs.","limitations":"As a review, the study does not present original experimental data and focuses on summarizing existing literature."},{"rthcId":"RPEP-06795","title":"Is There a Risk for Semaglutide Misuse? Focus on the Food and Drug Administration's FDA Adverse Events Reporting System (FAERS) Pharmacovigilance Dataset.","authors":"Chiappini, Stefania; Vickers-Smith, Rachel; Harris, Daniel; Papanti Pelletier, G Duccio; Corkery, John Martin; Guirguis, Amira; Martinotti, Giovanni; Sensi, Stefano L; Schifano, Fabrizio","year":2023,"journal":"Pharmaceuticals (Basel, Switzerland), 16(7)","doi":"10.3390/ph16070994","pmid":"37513906","tags":["glp-1-agonists","semaglutide"],"studyType":"Pharmacovigilance / Database Analysis","evidenceStrength":"low-moderate","keyFinding":"Semaglutide showed significantly higher signals for misuse-related adverse events compared to other GLP-1 drugs. Its proportional reporting ratios (PRR) for 'drug abuse' (4.05), 'drug withdrawal syndrome' (4.05), 'prescription drug used without a prescription' (3.60), and 'intentional product use issue' (1.80) were all significantly elevated (p<0.01) versus other GLP-1 receptor agonists.\n\nHowever, when compared to the phentermine-topiramate combination (an established weight loss drug with known misuse potential), semaglutide showed no significant differences in misuse signals. This suggests semaglutide's misuse signal may be in line with other weight loss medications rather than uniquely problematic.","whyItMatters":"As semaglutide went viral as a weight loss drug, reports emerged of people using it cosmetically without medical need, obtaining it without prescriptions, and diverting it from diabetic patients. This is the first study to formally quantify misuse signals in pharmacovigilance data. The findings raise questions about how to balance expanded access with appropriate use monitoring.","specificNumbers":"31,542 total AERs (Jan 2018–Dec 2022) · semaglutide: 8,249 reports (26.1%) · dulaglutide: 11,858 (37.6%) · semaglutide vs other GLP-1s: PRR 4.05 for drug abuse · PRR 4.05 for withdrawal · PRR 3.60 for use without prescription · all p<0.01","methodology":"Descriptive pharmacovigilance analysis of the FDA Adverse Event Reporting System (FAERS) database from January 2018 through December 2022. Researchers extracted all adverse event reports for seven GLP-1 receptor agonists and the phentermine-topiramate combination. Misuse-related events were identified using specific adverse event terms. Reporting odds ratios (ROR) and proportional reporting ratios (PRR) were calculated to detect safety signals.","limitations":"FAERS is a voluntary reporting system with well-known limitations: under-reporting, reporting bias (media attention on semaglutide likely inflated reports), and inability to establish causation. The 'drug abuse' and 'misuse' adverse event categories in FAERS are broad and may include cases of off-label use that aren't truly misuse. The study can't distinguish between recreational misuse and cosmetic off-label use by non-obese individuals. Media coverage of semaglutide may have disproportionately influenced reporting."},{"rthcId":"RPEP-06796","title":"Safety and effectiveness of dulaglutide 0.75 mg in Japanese patients with type 2 diabetes in real-world clinical practice: 36 month post-marketing observational study.","authors":"Chin, Rina; Nagaoka, Soshi; Nakasawa, Haru; Tanaka, Yoko; Inagaki, Nobuya","year":2023,"journal":"Journal of diabetes investigation, 14(2), 247-258","doi":"10.1111/jdi.13932","pmid":"36367417","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"7.37% of patients experienced adverse drug reactions, with a 0.76% reduction in glycated hemoglobin.","whyItMatters":"Understanding the real-world effectiveness and safety of dulaglutide helps inform treatment options for type 2 diabetes, especially in older adults.","specificNumbers":"","methodology":"This was a prospective, observational study conducted over 36 months, analyzing data from 3,136 patients using an electronic data capture system.","limitations":"The study is observational, which may limit the ability to establish causation, and it primarily involved Japanese patients, which may affect generalizability."},{"rthcId":"RPEP-06797","title":"Gly-Pro-Val-Gly-Pro-Ser Peptide Fish Collagen Improves Skin Moisture and Wrinkles with Ameliorated the Oxidative Stress and Pro-inflammatory Factors in Skin Photoaging Mimic Models.","authors":"Cho, Wonhee; Park, Jeongjin; Lee, Minhee; Park, Seong-Hoo; Jung, Jaeeun; Kim, Jinhak; Eun, Sangwon; Kim, Jinkyung","year":2023,"journal":"Preventive nutrition and food science, 28(1), 50-60","doi":"10.3746/pnf.2023.28.1.50","pmid":"37066027","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Fish collagen peptide supplementation produced comprehensive anti-photoaging effects across both in vitro and in vivo UV-B models:\n\n- Increased hyaluronic acid, sphingomyelin, and overall skin hydration by upregulating hyaluronic acid synthases 1-3, serine palmitoyltransferase 1, and ceramide synthase 4\n- Reduced pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) by suppressing IκBα, p65, and COX-2 protein expression\n- Boosted antioxidant enzyme activities\n- Downregulated collagen-degrading MMP-1, -2, and -9 pathways through JNK/c-Fos/c-Jun suppression\n- Upregulated new collagen production via TGF-β receptor I, collagen type I, procollagen type I, and Smad signaling","whyItMatters":"Skin photoaging is a universal concern, and collagen supplements are one of the most popular anti-aging products on the market. However, many claims about collagen peptides lack scientific evidence. This study provides detailed molecular evidence for how a specific fish collagen peptide sequence protects against UV damage through multiple pathways simultaneously — not just stimulating collagen production, but also reducing inflammation, boosting moisture, and blocking the enzymes that break down existing collagen.","specificNumbers":"","methodology":"Low molecular weight fish collagen peptide (Gly-Pro-Val-Gly-Pro-Ser) was derived from tilapia (Oreochromis niloticus). The study used UV-B irradiation to mimic sun-induced photoaging in both cell cultures (in vitro) and animal models (in vivo). Multiple molecular endpoints were measured using gene expression analysis (mRNA) and protein expression (Western blot), including inflammatory markers, antioxidant enzymes, skin hydration factors, collagen synthesis pathways, and collagen-degrading enzymes.","limitations":"This study used cell cultures and animal models, not human subjects. The UV-B exposure conditions in the lab may not perfectly replicate real-world sun exposure patterns. The specific peptide sequence (Gly-Pro-Val-Gly-Pro-Ser) may behave differently when consumed orally by humans — gastrointestinal digestion could break it down further before absorption. The animal species and exact dosing are not detailed in the abstract. No human clinical trial data supports these findings."},{"rthcId":"RPEP-06798","title":"Low-Molecular-Weight Fish Collagen Peptide (Valine-Glycine-Proline-Hydroxyproline-Glycine-Proline-Alanine-Glycine) Prevents Osteoarthritis Symptoms in Chondrocytes and Monoiodoacetate-Injected Rats.","authors":"Cho, Wonhee; Park, Jeongjin; Kim, Jinhee; Lee, Minhee; Park, So Jung; Kim, Kyung Seok; Jun, Woojin; Kim, Ok-Kyung; Lee, Jeongmin","year":2023,"journal":"Marine drugs, 21(12)","doi":"10.3390/md21120608","pmid":"38132929","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The low-molecular-weight fish collagen peptide (VGPHGPAG) demonstrated dual protective mechanisms:\n\n**Anti-catabolic effects:**\n- Increased aggrecan, collagen type I, collagen type II, TIMP-1, and TIMP-3 (protective matrix components)\n- Decreased phosphorylation of Smad, MMP-3, and MMP-13 (destructive enzymes)\n\n**Anti-inflammatory and anti-apoptotic effects:**\n- Suppressed inflammation pathways in LPS-treated chondrocytes and MIA-induced OA cartilage\n- Suppressed apoptosis pathways, preventing chondrocyte death\n\nThese effects were consistent across both in vitro (H₂O₂ or LPS-treated primary chondrocytes) and in vivo (MIA-injected rat osteoarthritis) models.","whyItMatters":"Current osteoarthritis treatments only manage pain — there are no approved therapies that protect or rebuild cartilage. If specific collagen peptides can slow cartilage destruction and reduce joint inflammation, they could become the first disease-modifying approach for OA available as a dietary supplement. The precise sequence identification (VGPHGPAG) allows for standardized product development and quality control.","specificNumbers":"","methodology":"Two complementary approaches: (1) In vitro: primary chondrocytes were stressed with H₂O₂ (oxidative stress) or LPS (inflammatory stimulus) and treated with LMWCP to assess cell survival, matrix production, and inflammation markers. (2) In vivo: rats received monoiodoacetate (MIA) joint injection to induce osteoarthritis, then were treated with LMWCP and assessed for cartilage degradation, inflammation, and apoptosis in joint tissue.","limitations":"All data is from cell cultures and a rat osteoarthritis model — human clinical trials are needed. The MIA rat model causes rapid, chemically-induced cartilage damage that doesn't fully represent the slow, chronic progression of human OA. Oral bioavailability of the specific 8-amino-acid peptide is unclear — whether it survives digestion intact to reach joint tissue in humans was not assessed. Dosing, treatment duration, and long-term effects in animals were not detailed in the abstract."},{"rthcId":"RPEP-06799","title":"Inhibition of angiotensin converting enzyme increases PKCβI isoform expression via activation of substance P and bradykinin receptors in cultured astrocytes of mice.","authors":"Choi, Jae-Gyun; Choi, Sheu-Ran; Kang, Dong-Wook; Shin, Hyun Jin; Lee, Miae; Hwang, Jungmo; Kim, Hyun-Woo","year":2023,"journal":"Journal of veterinary science, 24(2), e26","doi":"10.4142/jvs.22275","pmid":"37012034","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Captopril increased PKCβI expression in astrocytes, with significant increases in substance P and bradykinin levels.","whyItMatters":"Understanding how ACE inhibitors affect brain cell signaling can help in developing treatments for neurological conditions. This research may provide insights into the mechanisms of pain and inflammation in the brain.","specificNumbers":"","methodology":"The study used immunocytochemistry and Western blot analysis on primary cultured astrocytes to assess protein levels and expression.","limitations":"The study was conducted in cultured astrocytes, which may not fully replicate in vivo conditions in living organisms."},{"rthcId":"RPEP-06800","title":"Thymosin Beta 4 Inhibits LPS and ATP-Induced Hepatic Stellate Cells via the Regulation of Multiple Signaling Pathways.","authors":"Choi, Jihye; Cho, Yunsang; Choi, Hwal; Lee, Sangmin; Han, Hyeju; Lee, Jeonghyeon; Kwon, Jungkee","year":2023,"journal":"International journal of molecular sciences, 24(4)","doi":"10.3390/ijms24043439","pmid":"36834849","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tβ4 significantly suppressed the activation of the NLRP3 inflammasome and related inflammatory markers.","whyItMatters":"This research highlights a potential therapeutic role for Tβ4 in managing liver inflammation and fibrosis, which are common issues in various liver diseases.","specificNumbers":"","methodology":"The study used RAW 264.7 and LX-2 cells, priming them with LPS and stimulating with ATP to activate the NLRP3 inflammasome, while assessing the effects of Tβ4.","limitations":"The study was conducted in vitro, so results may not directly translate to human conditions."},{"rthcId":"RPEP-06801","title":"Ghrelin Downregulates Lipopolysaccharide/ Leptin-Induced MUC5AC Expression in Human Nasal Epithelial Cells.","authors":"Choi, Yoon Seok; Na, Hyung Gyun; Bae, Chang Hoon; Song, Si-Youn; Kim, Yong-Dae","year":2023,"journal":"Clinical and experimental otorhinolaryngology, 16(1), 49-58","doi":"10.21053/ceo.2022.00857","pmid":"36177976","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Ghrelin downregulated LPS/leptin-induced MUC5AC expression in nasal epithelial cells.","whyItMatters":"Understanding ghrelin's role in mucus regulation could lead to new treatments for chronic nasal inflammation in obese individuals. This research highlights a potential therapeutic pathway for managing obesity-related sinonasal diseases.","specificNumbers":"","methodology":"The study used various laboratory techniques, including PCR and Western blotting, to assess the effects of ghrelin on mucus expression in human nasal epithelial cells.","limitations":"The study was conducted in vitro, meaning results may not fully translate to human patients. Further research is needed to confirm findings in clinical settings."},{"rthcId":"RPEP-06802","title":"Purification and Characterization of Novel Antihypertensive and Antioxidative Peptides From Whey Protein Fermentate: In Vitro, In Silico, and Molecular Interactions Studies.","authors":"Chopada, Keval; Basaiawmoit, Bethsheba; Sakure, Amar A; Maurya, Ruchika; Bishnoi, Mahendra; Kondepudi, Kanthi Kiran; Solanki, Divyang; Singh, B P; Padhi, Srichandan; Rai, Amit Kumar; Liu, Zhenbin; Mishra, B K; Hati, Subrota","year":2023,"journal":"Journal of the American Nutrition Association, 42(6), 598-617","doi":"10.1080/27697061.2022.2110966","pmid":"36416542","tags":["food-derived-peptides","cardiovascular"],"studyType":"in-vitro","evidenceStrength":"low","keyFinding":"Researchers fermented whey protein concentrate using a co-culture of Lactobacillus paracasei and Saccharomyces cerevisiae (yeast) and identified novel peptides with ACE-inhibitory (blood pressure lowering), antioxidant, and anti-inflammatory properties. Maximum proteolytic activity was 6.50 mg/mL at 37°C and 8.59 mg/mL at 25°C after 48 hours of fermentation.\n\nTwo specific peptides — AFLDSRTR and ILGAFIQIITFR — were identified and characterized. Molecular docking showed they interact with human myeloperoxidase, an enzyme involved in inflammation. The whey fermentate also reduced inflammation in macrophage cell cultures exposed to bacterial toxins (LPS).","whyItMatters":"Whey protein is already one of the most widely consumed protein supplements. This study shows that fermenting it with specific bacteria and yeast produces bioactive peptides that could lower blood pressure, fight oxidative stress, and reduce inflammation — potentially turning a common protein supplement into a functional food with cardiovascular benefits.","specificNumbers":"Proteolytic activity: 6.50 mg/mL (37°C) and 8.59 mg/mL (25°C) at 48h · Protein range: 10-70 kDa · Key peptides: AFLDSRTR, ILGAFIQIITFR · Tested at 12, 24, 36, 48h intervals · Inoculation rates: 1.5%, 2.0%, 2.5%","methodology":"Whey protein concentrate was co-fermented with Lactobacillus paracasei (at 37°C) and Saccharomyces cerevisiae (at 25°C) at varying time points and inoculation rates. Bioactive peptides were separated using RP-HPLC and identified by mass spectrometry. ACE inhibition, antioxidant activity, and anti-inflammatory effects were tested in vitro. Anti-inflammatory activity was assessed on RAW 264.7 macrophages stimulated with LPS. Molecular docking simulated peptide-enzyme interactions.","limitations":"Entirely in vitro and in silico — no animal or human studies. ACE inhibition in a test tube doesn't guarantee blood pressure reduction in people. The peptides may be digested before reaching their targets when consumed orally. Molecular docking predicts binding but doesn't confirm biological activity in vivo."},{"rthcId":"RPEP-06803","title":"Control of Helicobacter pylori with engineered probiotics secreting selective guided antimicrobial peptides.","authors":"Choudhury, Ankan; Ortiz, Patrick S; Young, Mikaeel; Mahmud, Md Toslim; Stoffel, Ryan T; Greathouse, K Leigh; Kearney, Christopher M","year":2023,"journal":"Microbiology spectrum, 11(5), e0201423","doi":"10.1128/spectrum.02014-23","pmid":"37712669","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06804","title":"Increasing expression of STING by ERα antagonizes LCN2 downregulation during chronic endometritis.","authors":"Chu, Min; He, Shunzhi; Zhao, Huishan; Yin, Shuyuan; Liu, Zhenteng; Zhang, Wei; Liu, Xuemei; Bao, Hongchu","year":2023,"journal":"Journal of reproductive immunology, 160, 104167","doi":"10.1016/j.jri.2023.104167","pmid":"37952294","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"ERα upregulates STING expression, which in turn modulates LCN2 antimicrobial peptide expression.","whyItMatters":"Understanding how estrogen influences immune responses can help in developing treatments for chronic endometritis, potentially improving fertility outcomes.","specificNumbers":"","methodology":"The study examined human endometrial tissues for antimicrobial peptide expression and assessed the effects of estrogen receptor inhibitors.","limitations":"The study is limited to human tissue samples and does not explore the effects in live subjects or clinical settings."},{"rthcId":"RPEP-06805","title":"The glucagon-like peptide-1 (GLP-1) analogue semaglutide reduces alcohol drinking and modulates central GABA neurotransmission.","authors":"Chuong, Vicky; Farokhnia, Mehdi; Khom, Sophia; Pince, Claire L; Elvig, Sophie K; Vlkolinsky, Roman; Marchette, Renata Cn; Koob, George F; Roberto, Marisa; Vendruscolo, Leandro F; Leggio, Lorenzo","year":2023,"journal":"JCI insight, 8(12)","doi":"10.1172/jci.insight.170671","pmid":"37192005","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide demonstrated broad anti-alcohol effects across models and species:\n- Dose-dependently reduced binge-like alcohol drinking in mice (drinking-in-the-dark model)\n- Also reduced intake of other caloric/noncaloric solutions, suggesting a general reward-reducing effect\n- Reduced binge-like and dependence-induced alcohol drinking in rats\n- Effects observed in both male and female animals\n\nMechanistically, semaglutide increased spontaneous inhibitory postsynaptic current (sIPSC) frequency in central amygdala (CeA) and infralimbic cortex (ILC) neurons from alcohol-naive rats, indicating enhanced GABA release. However, this effect was absent in alcohol-dependent rats, suggesting chronic alcohol exposure may alter GLP-1 receptor-GABA interactions.","whyItMatters":"Alcohol use disorder affects approximately 283 million people worldwide and has limited effective pharmacotherapies. Semaglutide is already widely available and well-characterized for safety, meaning it could potentially be repurposed for AUD much faster than developing an entirely new drug. The NIH/NIDA-affiliated research team behind this study and the growing anecdotal evidence from semaglutide users add momentum to clinical trials already underway.","specificNumbers":"","methodology":"Multiple rodent models were used: a drinking-in-the-dark procedure for binge-like drinking in male and female mice, and both binge-like and dependence-induced drinking models in male and female rats. Electrophysiology experiments measured spontaneous inhibitory postsynaptic currents (sIPSCs) in central amygdala and infralimbic cortex neurons from both alcohol-naive and alcohol-dependent rats after acute semaglutide application.","limitations":"All data is from rodent models, which don't fully replicate human drinking patterns or the complexity of alcohol use disorder. The GABA modulation effect was absent in alcohol-dependent rats, raising questions about efficacy in heavily dependent individuals. Semaglutide also reduced non-alcohol caloric intake, making it unclear whether the anti-alcohol effect is specific to alcohol reward or reflects a general reduction in consumption. Human clinical trial data is needed to confirm these findings."},{"rthcId":"RPEP-06806","title":"An evaluation of bremelanotide injection for the treatment of hypoactive sexual desire disorder.","authors":"Cipriani, Sarah; Alfaroli, Chiara; Maseroli, Elisa; Vignozzi, Linda","year":2023,"journal":"Expert opinion on pharmacotherapy, 24(1), 15-21","doi":"10.1080/14656566.2022.2132144","pmid":"36242769","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Bremelanotide resulted in a significant change in validated questionnaires, but the clinical benefit is modest.","whyItMatters":"Understanding the efficacy and safety of bremelanotide can help address sexual dysfunction in women, a significant but often overlooked issue.","specificNumbers":"","methodology":"The study involved a literature search of peer-reviewed publications on bremelanotide's pharmacotherapy.","limitations":"The study acknowledges the challenges of conducting clinical trials in this area, including high placebo effects and biases in outcome measures."},{"rthcId":"RPEP-06807","title":"Low-power microwaves: a cell-compatible physical treatment to enhance the mechanical properties of self-assembling peptides.","authors":"Ciulla, Maria Gessica; Marchini, Amanda; Gazzola, Jacopo; Sambrotta, Manuel; Gelain, Fabrizio","year":2023,"journal":"Nanoscale, 15(38), 15840-15854","doi":"10.1039/d3nr02738d","pmid":"37747054","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Low-power microwaves increased stiffness and resilience of SAPs without altering their biomimetic properties.","whyItMatters":"This research offers a safer, more efficient method for enhancing peptide materials used in tissue engineering, potentially improving patient outcomes in regenerative medicine.","specificNumbers":"","methodology":"The study utilized rheology, atomic force microscopy, Thioflavin-T assay, and Fourier transform infrared tests to analyze the effects of microwave treatment on SAPs.","limitations":"The study primarily focuses on the mechanical properties of SAPs and does not address long-term effects or performance in vivo."},{"rthcId":"RPEP-06808","title":"Growth hormone-releasing hormone receptor antagonist MIA-602 attenuates cardiopulmonary injury induced by BSL-2 rVSV-SARS-CoV-2 in hACE2 mice.","authors":"Condor Capcha, Jose M; Kamiar, Ali; Robleto, Emely; Saad, Ali G; Cui, Tengjiao; Wong, Amanda; Villano, Jason; Zhong, William; Pekosz, Andrew; Medina, Edgar; Cai, Renzhi; Sha, Wei; Ranek, Mark J; Webster, Keith A; Schally, Andrew V; Jackson, Robert M; Shehadeh, Lina A","year":2023,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 120(48), e2308342120","doi":"10.1073/pnas.2308342120","pmid":"37983492","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Daily subcutaneous MIA-602 treatment in rVSV-SARS-CoV-2-infected K18-hACE2 transgenic mice produced: weight recovery (vs. continued loss in vehicle group), reduced lung perivascular inflammation and pneumonia, decreased ICAM-1 expression in both lung and heart tissue, rescued respiratory rate and normalized airflow parameters (Penh, Rpef, expiratory parameters), and normalized inflammation and necroptosis markers (ZBP1, pMLKL) that were heightened by infection. RNASeq analysis confirmed an anti-inflammatory and pro-survival mechanism of action. The rVSV-SARS-CoV-2 model showed similar pathology to native SARS-CoV-2 infection (~60% infectivity).","whyItMatters":"Despite vaccines, severe COVID-19 and other respiratory virus infections continue to cause significant morbidity and mortality. Current treatments are limited. MIA-602 represents a peptide-based approach that addresses the inflammatory cascade driving lung damage rather than targeting the virus itself — making it potentially useful across different respiratory infections. The additional heart protection is clinically important since cardiac complications are a major cause of COVID-related death.","specificNumbers":"","methodology":"K18-hACE2 transgenic mice (which express the human ACE2 receptor) were infected with either native SARS-CoV-2 or BSL-2-compliant rVSV-eGFP-SARS-CoV-2-Spike virus. Model validation confirmed similar patterns of weight loss, infectivity, and histopathology between the two. Infected mice (n=7-8 per group) received daily subcutaneous MIA-602 or vehicle. Unrestrained plethysmography measured respiratory function on days 0, 3, and 5. At day 5, tissues were collected for histopathology, protein/gene expression, and RNASeq analysis.","limitations":"Mouse model with a surrogate virus — while validated against native SARS-CoV-2, it may not fully replicate human COVID-19 pathophysiology. The 5-day study period is very short. Group sizes (7-8 mice) are modest. The study assessed acute injury prevention but not long-term outcomes. Optimal dosing, timing of treatment initiation, and safety profile in the context of active infection need further characterization."},{"rthcId":"RPEP-06809","title":"Discovery of an orally effective double-stapled peptide for reducing ovariectomy-induced bone loss in mice.","authors":"Cong, Wei; Shen, Huaxing; Liao, Xiufei; Zheng, Mengjun; Kong, Xianglong; Wang, Zhe; Chen, Si; Li, Yulei; Hu, Honggang; Li, Xiang","year":2023,"journal":"Acta pharmaceutica Sinica. B, 13(9), 3770-3781","doi":"10.1016/j.apsb.2023.05.004","pmid":"37719364","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The double-stapled peptide FRNC-1 is the first orally effective peptide validated as a therapeutic candidate for postmenopausal osteoporosis. It inhibited bone resorption by mature osteoclasts through specific inhibition of phosphorylated GSK-3β, showed markedly improved helical content and proteolytic resistance compared to its linear form, and effectively prevented osteoclast activation and improved bone density in ovariectomized mice after both intravenous and oral (intragastric) administration.","whyItMatters":"Oral delivery of peptide drugs has been one of the biggest challenges in pharmaceutical development — most peptides are destroyed by stomach acid and digestive enzymes. Achieving oral efficacy with a stapled peptide for osteoporosis is a breakthrough that could transform how peptide drugs are administered, moving from injections to pills for a condition affecting hundreds of millions of postmenopausal women worldwide.","specificNumbers":"Double-stapled peptide FRNC-1 · improved helical content vs linear form · effective via IV and oral routes · GSK-3β phosphorylation inhibition · improved bone density in OVX mice","methodology":"Researchers designed and synthesized the double-stapled peptide FRNC-1 using all-hydrocarbon stapling. They characterized helical content and proteolytic stability compared to the linear form. In vitro, they tested FRNC-1's effect on mature osteoclast bone resorption and GSK-3β phosphorylation. In vivo, ovariectomized mice (a standard postmenopausal osteoporosis model) received FRNC-1 by both intravenous injection and oral (intragastric) administration, with bone density as the primary outcome.","limitations":"Mouse model — ovariectomized mice don't fully replicate human postmenopausal osteoporosis. Oral bioavailability numbers, specific dosing, and treatment duration are not detailed in the abstract. Long-term safety, especially effects on non-bone tissues where GSK-3β is important, requires investigation. Human pharmacokinetics and efficacy studies are needed."},{"rthcId":"RPEP-06810","title":"Glucagon-like peptide 1 (GLP-1) receptor agonists as a protective factor for incident depression in patients with diabetes mellitus: A systematic review.","authors":"Cooper, Daniel H; Ramachandra, Ranuk; Ceban, Felicia; Di Vincenzo, Joshua D; Rhee, Taeho Greg; Mansur, Rodrigo B; Teopiz, Kayla M; Gill, Hartej; Ho, Roger; Cao, Bing; Lui, Leanna M W; Jawad, Muhammad Youshay; Arsenault, Juliet; Le, Gia Han; Ramachandra, Diluk; Guo, Ziji; McIntyre, Roger S","year":2023,"journal":"Journal of psychiatric research, 164, 80-89","doi":"10.1016/j.jpsychires.2023.05.041","pmid":"37331261","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Two out of four studies showed a significant reduction in depression risk with GLP-1 receptor agonists.","whyItMatters":"Understanding the potential mental health benefits of diabetes medications could improve patient care. Further research may lead to better treatment options for preventing depression in diabetic patients.","specificNumbers":"","methodology":"A systematic review of four retrospective observational studies on GLP-1 receptor agonists and depression risk in diabetes patients.","limitations":"The study faced high interstudy heterogeneity, limited literature, and a lack of controlled trials."},{"rthcId":"RPEP-06811","title":"Efficacy of Liraglutide in Obesity in Children and Adolescents: Systematic Review and Meta-Analysis of Randomized Controlled Trials.","authors":"Cornejo-Estrada, Alejandra; Nieto-Rodríguez, Carlos; León-Figueroa, Darwin A; Moreno-Ramos, Emilly; Cabanillas-Ramirez, Cielo; Barboza, Joshuan J","year":2023,"journal":"Children (Basel, Switzerland), 10(2)","doi":"10.3390/children10020208","pmid":"36832337","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06812","title":"Neuroprotective Mechanisms of Amylin Receptor Activation, Not Antagonism, in the APP/PS1 Mouse Model of Alzheimer's Disease.","authors":"Corrigan, Rachel R; Labrador, Luis; Grizzanti, John; Mey, Megan; Piontkivska, Helen; Casadesús, Gemma","year":2023,"journal":"Journal of Alzheimer's disease : JAD, 91(4), 1495-1514","doi":"10.3233/JAD-221057","pmid":"36641678","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Pramlintide (delivered systemically via IP injection) improved cognitive function in APP/PS1 Alzheimer's model mice even when central amylin receptors were simultaneously blocked with AC187 (delivered ICV). This suggests pramlintide's cognitive benefits operate through peripheral metabolic mechanisms rather than direct central receptor activation.\n\nCentral amylin receptor inhibition with AC187 increased amyloid-beta pathology in female APP/PS1 mice — an effect mitigated by peripheral pramlintide. Transcriptomic analysis revealed sexually dimorphic neuroprotective mechanisms: oxidative stress protection pathways in females and membrane stability/reduced neuronal excitability markers in males.","whyItMatters":"The amylin system has been controversial in Alzheimer's research — some studies show amylin worsens pathology while others show protection. This study helps resolve the debate by showing that amylin receptor activation is neuroprotective (blocking it worsens pathology), while pramlintide's cognitive benefits may work through peripheral metabolic improvement. The sex-specific mechanisms add important nuance for future drug development.","specificNumbers":"","methodology":"APP/PS1 transgenic Alzheimer's model mice received the amylin analog pramlintide systemically (IP) at previously identified therapeutic doses while simultaneously receiving the amylin receptor antagonist AC187 centrally (ICV). Cognitive function was assessed behaviorally, amyloid-beta pathology was measured, and transcriptomic analysis was performed to identify neuroprotective mechanisms. Both male and female mice were studied to assess sex differences.","limitations":"This is a mouse study using a transgenic Alzheimer's model (APP/PS1) that doesn't fully replicate human Alzheimer's disease. The ICV delivery of the antagonist is invasive and artificial. Sample sizes per group were not specified in the abstract. The transcriptomic findings suggest mechanisms but don't prove them. The sex-specific effects may differ in humans. Pramlintide doses may not translate directly to human therapeutic ranges."},{"rthcId":"RPEP-06813","title":"Encapsulated Peptides and Proteins with an Effect on Satiety.","authors":"Costa, Rafael O de A; Passos, Thaís S; Silva, Eloyse Mikaelly de S; Dos Santos, Nicolle Caroline S; Morais, Ana Heloneida de A","year":2023,"journal":"Nanomaterials (Basel, Switzerland), 13(7)","doi":"10.3390/nano13071166","pmid":"37049259","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Encapsulation of proteins and peptides can enhance weight loss efficiency and reduce appetite-related hormone levels in obese animals.","whyItMatters":"Understanding how encapsulated peptides and proteins work could lead to more effective obesity treatments. This research may provide new avenues for improving nutritional strategies against obesity.","specificNumbers":"","methodology":"This is an integrative review that analyzes various studies on encapsulated peptides and proteins.","limitations":"The review primarily focuses on animal studies, which may not fully translate to human outcomes."},{"rthcId":"RPEP-06814","title":"A novel peptide isolated from Aphonopelma chalcodes tarantula venom with benefits on pancreatic islet function and appetite control.","authors":"Coulter-Parkhill, A; Dobbin, Swm; Tanday, N; Gault, V A; McClean, S; Irwin, N","year":2023,"journal":"Biochemical pharmacology, 212, 115544","doi":"10.1016/j.bcp.2023.115544","pmid":"37044298","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The novel 28-amino-acid peptide Δ-TRTX-AC1, isolated from Aphonopelma chalcodes tarantula venom, demonstrated multiple beneficial effects: it evoked glucose-dependent insulin secretion from beta cells via KATP and calcium channel signaling pathways, enhanced beta-cell proliferation, and provided significant protection against cytokine-induced apoptosis.\n\nIn C57BL/6 mice at 250 nmol/kg, Δ-TRTX-AC1 decreased blood glucose levels and produced a significant satiating effect. While it did not enhance exenatide's glucose-lowering effects, it significantly augmented exenatide-mediated appetite suppression, suggesting complementary mechanisms of action. The peptide adopted a characteristic inhibitor cysteine knot (ICK) structure and was non-toxic to beta cells.","whyItMatters":"The diabetes drug exenatide was originally discovered in Gila monster venom, proving that venomous animals are a rich source of therapeutic peptides. This study extends that approach to tarantula venom, identifying a peptide with a unique combination of benefits — insulin secretion, beta-cell protection, and appetite suppression — that could complement existing GLP-1 therapies for diabetes and obesity.","specificNumbers":"","methodology":"Researchers isolated and sequenced the peptide from tarantula venom, then synthesized it and confirmed its structure. They tested safety and insulin-secretory effects in BRIN BD11 cells and murine pancreatic islets, investigating signaling pathways (KATP channels, calcium channels). Beta-cell proliferation and protection against cytokine-induced apoptosis were assessed. In vivo effects on blood glucose and satiety were tested in C57BL/6 mice, alone and in combination with exenatide.","limitations":"All experiments were conducted in vitro or in normal (non-diabetic) mice, so efficacy in diabetic models or humans is unknown. The mechanism of the appetite-suppressing effect was not fully elucidated. Only acute single-dose effects were tested — chronic dosing safety and sustained efficacy need evaluation. The peptide's pharmacokinetics (how long it lasts in the body) were not detailed."},{"rthcId":"RPEP-06815","title":"Peptides originally derived from Chilobrachys jingzhao tarantula venom possess beneficial effects on pancreatic beta cell health and function.","authors":"Coulter-Parkhill, A; Gault, V A; McClean, S; Irwin, N","year":2023,"journal":"European journal of pharmacology, 954, 175855","doi":"10.1016/j.ejphar.2023.175855","pmid":"37391009","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Jingzhaotoxin IX and XI peptides improved insulin secretion and beta-cell proliferation without toxicity.","whyItMatters":"These findings suggest that tarantula venom peptides could be a new avenue for diabetes treatment, potentially improving existing therapies.","specificNumbers":"","methodology":"The study involved in vitro assessments of beta-cell function and in vivo tests in mice to evaluate glucose-lowering effects.","limitations":"The study was conducted in mice, and results may not directly translate to humans; further research is needed to confirm efficacy and safety."},{"rthcId":"RPEP-06816","title":"The Repurposing of Non-Peptide Neurokinin-1 Receptor Antagonists as Antitumor Drugs: An Urgent Challenge for Aprepitant.","authors":"Coveñas, Rafael; Rodríguez, Francisco D; Robinson, Prema; Muñoz, Miguel","year":2023,"journal":"International journal of molecular sciences, 24(21)","doi":"10.3390/ijms242115936","pmid":"37958914","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Aprepitant shows a broad-spectrum anticancer effect against many tumor types.","whyItMatters":"Repurposing Aprepitant could provide a new strategy for cancer treatment, potentially improving patient quality of life. This approach may lead to more effective therapies for various cancers.","specificNumbers":"","methodology":"This is a review article summarizing existing research on NK-1R antagonists and their potential as anticancer drugs.","limitations":"As a review, it does not present original experimental data; further clinical trials are needed to validate findings."},{"rthcId":"RPEP-06817","title":"Disparate Regions of the Human Chemokine CXCL10 Exhibit Broad-Spectrum Antimicrobial Activity against Biodefense and Antibiotic-Resistant Bacterial Pathogens.","authors":"Crawford, Matthew A; Ward, Amanda E; Gray, Vincent; Bailer, Peter; Fisher, Debra J; Kubicka, Ewa; Cui, Zixian; Luo, Qinmo; Gray, Mary C; Criss, Alison K; Lum, Lawrence G; Tamm, Lukas K; Letteri, Rachel A; Hughes, Molly A","year":2023,"journal":"ACS infectious diseases, 9(1), 122-139","doi":"10.1021/acsinfecdis.2c00456","pmid":"36475632","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Peptide P1 effectively killed Bacillus anthracis and antibiotic-resistant strains of Klebsiella pneumoniae and others.","whyItMatters":"With rising antibiotic resistance, finding new antimicrobial agents is crucial for treating infections. CXCL10-derived peptides could offer a new therapeutic approach.","specificNumbers":"","methodology":"The study used peptide mapping and structure/function analyses to identify antimicrobial regions of CXCL10.","limitations":"The study primarily focuses on in vitro results, which may not fully translate to in vivo effectiveness in humans."},{"rthcId":"RPEP-06818","title":"Targeting β Cells with Cathelicidin Nanomedicines Improves Insulin Function and Pancreas Regeneration in Type 1 Diabetic Rats.","authors":"Cristelo, Cecília; Nunes, Rute; Pinto, Soraia; Marques, Joana Moreira; Gama, Francisco Miguel; Sarmento, Bruno","year":2023,"journal":"ACS pharmacology & translational science, 6(10), 1544-1560","doi":"10.1021/acsptsci.3c00218","pmid":"37854630","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The treatment led to a significant reduction in hyperglycemia and increased β cell mass in diabetic rats.","whyItMatters":"This research could lead to new treatments for type 1 diabetes, a condition currently without a cure. Improving β cell function could enhance insulin production and blood sugar control.","specificNumbers":"","methodology":"The study involved creating nanoparticles loaded with the peptide LLKKK18 and testing their effects on diabetic rats.","limitations":"The study was conducted in rats, and results may not directly translate to humans. Further research is needed to assess long-term effects and safety."},{"rthcId":"RPEP-06819","title":"Evaluation of the therapeutic efficacy of 213Bi-labelled DOTA-conjugated alpha-melanocyte stimulating hormone peptide analogues in melanocortin-1 receptor positive preclinical melanoma model.","authors":"Csikos, Csaba; Képes, Zita; Fekete, Anikó; Vágner, Adrienn; Nagy, Gábor; Gyuricza, Barbara; Arató, Viktória; Kárpáti, Levente; Mándity, István; Bruchertseifer, Frank; Halmos, Gábor; Szikra, Dezső; Trencsényi, György","year":2023,"journal":"International journal of pharmaceutics, 644, 123344","doi":"10.1016/j.ijpharm.2023.123344","pmid":"37634663","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The NAPamide-treated group had the smallest tumor volumes on day 10 post-treatment.","whyItMatters":"This research could lead to more effective targeted therapies for melanoma, a challenging cancer to treat. It highlights the potential of using receptor-targeted radiotherapy in cancer management.","specificNumbers":"","methodology":"The study involved injecting mice with melanoma tumors with two different peptide treatments and assessing tumor size and imaging results over several days.","limitations":"The study was conducted in mice, which may not fully represent human responses. Further research is needed to confirm these findings in clinical settings."},{"rthcId":"RPEP-06820","title":"Discovery of ACE Inhibitory Peptides Derived from Green Coffee Using In Silico and In Vitro Methods.","authors":"Dai, Haopeng; He, Min; Hu, Guilin; Li, Zhongrong; Al-Romaima, Abdulbaset; Wu, Zhouwei; Liu, Xiaocui; Qiu, Minghua","year":2023,"journal":"Foods (Basel, Switzerland), 12(18)","doi":"10.3390/foods12183480","pmid":"37761189","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Two novel peptides, IIPNEVY and ITPPVMLPP, were identified from green coffee bean protein hydrolysates with ACE inhibitory IC50 values of 57.54 and 40.37 μM, respectively. Molecular docking revealed both peptides bind near the S1 active pocket of ACE to form stable enzyme-peptide complexes.\n\nThe peptides work through different inhibition mechanisms: IIPNEVY acts as a noncompetitive inhibitor (binding to the enzyme at a site separate from the substrate), while ITPPVMLPP is a mixed-type inhibitor (can bind both the free enzyme and the enzyme-substrate complex). Five candidate peptides were initially identified through in silico screening, with these two showing the strongest activity in vitro.","whyItMatters":"ACE inhibitors are one of the most widely prescribed drug classes for high blood pressure. Finding natural food-derived peptides that block the same enzyme could lead to functional foods or nutraceuticals for blood pressure management with potentially fewer side effects than pharmaceutical ACE inhibitors. Coffee is one of the most consumed beverages globally, making coffee-derived bioactive peptides particularly interesting from a dietary perspective.","specificNumbers":"","methodology":"Green coffee bean proteins were extracted and digested using two enzymes (alcalase and thermolysin) to produce peptide fragments. The resulting peptides were identified using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Computer-based (in silico) screening predicted which peptides might inhibit ACE. The top candidates were then tested in vitro for ACE inhibition, and molecular docking was used to model how the peptides interact with the enzyme. Inhibition kinetics were determined using Lineweaver-Burk plots.","limitations":"This is entirely an in silico and in vitro study — no animal or human testing was conducted. The IC50 values in the micromolar range are relatively modest compared to pharmaceutical ACE inhibitors. It's unknown whether these peptides would survive digestion intact or be absorbed into the bloodstream at active concentrations. The amount of these peptides in a typical cup of coffee is likely negligible, and concentrated supplementation would be needed for any blood pressure effect."},{"rthcId":"RPEP-06821","title":"Effects of site-directed mutagenesis of GLP-1 and glucagon receptors on signal transduction activated by dual and triple agonists.","authors":"Darbalaei, Sanaz; Chang, Ru-Lue; Zhou, Qing-Tong; Chen, Yan; Dai, An-Tao; Wang, Ming-Wei; Yang, De-Hua","year":2023,"journal":"Acta pharmacologica Sinica, 44(2), 421-433","doi":"10.1038/s41401-022-00962-y","pmid":"35953646","tags":["glp-1-agonists","peptide-engineering"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Using site-directed mutagenesis, researchers identified specific amino acid residues in the GLP-1 receptor (GLP-1R) and glucagon receptor (GCGR) that are critical for activation by multi-target peptide agonists. Three dual agonists (peptide 15, MEDI0382, and SAR425899) and one triple agonist (peptide 20) were compared to the natural hormones GLP-1 and glucagon across two signaling pathways — cAMP accumulation and ERK1/2 phosphorylation.\n\nThe results revealed distinct residue networks that control how each multi-target agonist activates these receptors, and showed that the signaling patterns differ significantly between the agonists. This means each dual/triple agonist has its own unique 'fingerprint' of receptor activation, which could be exploited to design drugs with optimized therapeutic profiles and reduced side effects.","whyItMatters":"Multi-target peptide agonists like tirzepatide (dual GIP/GLP-1) and emerging triple agonists (GLP-1/GIP/glucagon) represent the next wave of metabolic disease drugs. But designing a single peptide that hits multiple receptors with the right balance of activity is extraordinarily challenging. This study provides a molecular roadmap — identifying which receptor residues matter most for each agonist — that could enable rational design of next-generation multi-target peptides with optimized efficacy and safety profiles.","specificNumbers":"3 dual agonists tested (peptide 15, MEDI0382, SAR425899) · 1 triple agonist (peptide 20) · 2 signaling pathways (cAMP, pERK1/2) · 2 receptors (GLP-1R, GCGR) · distinct residue networks identified for each agonist","methodology":"Structure-based site-directed mutagenesis was used to create receptor variants with specific amino acid changes in GLP-1R and GCGR. Pharmacological assays measured agonist-induced cAMP accumulation and ERK1/2 phosphorylation for three dual agonists and one triple agonist compared to native GLP-1 and glucagon. The results mapped residue networks critical for multi-target agonist signaling at each receptor.","limitations":"This is entirely an in vitro study using mutant receptors in cell systems, which may not capture the full complexity of receptor signaling in living organisms. Only two signaling pathways were measured; other downstream effects (β-arrestin recruitment, receptor internalization) were not assessed. The clinical relevance of the specific signaling differences identified requires validation in animal models. The study examines receptors in isolation rather than in the context of receptor dimerization or interaction with accessory proteins."},{"rthcId":"RPEP-06822","title":"Chitosan hydrogels with MK2 inhibitor peptide-loaded nanoparticles to treat atopic dermatitis.","authors":"Dartora, Vanessa F C; Passos, Julia Sapienza; Osorio, Blanca; Hung, Ruei-Chun; Nguyen, Michael; Wang, Aijun; Panitch, Alyssa","year":2023,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 362, 591-605","doi":"10.1016/j.jconrel.2023.08.061","pmid":"37660990","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The H-NP-YARA system (chitosan hydrogel with YARA-loaded pNIPAM nanoparticles) demonstrated:\n\n- Loading efficiency: >50% for YARA peptide in nanoparticles\n- Sustained release: up to 120 hours from both nanoparticles and hydrogels\n- Skin penetration: 2-fold (NP alone) and 4-fold (hydrogel-NP) more YARA delivered into viable skin layers vs. free peptide at 12 hours, in both intact and impaired barrier conditions\n- In vitro inflammation: NP-YARA and H-NP-YARA reduced inflammatory cytokines up to 20-fold compared to untreated inflamed human keratinocytes\n- Ex vivo skin model: NP-YARA reduced IL-1β, IL-6, and TNF-α up to 3.3-fold; H-NP-YARA reduced them up to 17-fold compared to drug in solution\n- Hydrogel maintained porous structure after nanoparticle incorporation (SEM confirmed)","whyItMatters":"Atopic dermatitis affects up to 20% of children and 10% of adults worldwide, and long-term steroid use causes skin atrophy and other serious side effects. A peptide-based anti-inflammatory treatment delivered through a hydrogel could provide effective inflammation control without steroid-related damage. The 17-fold reduction in inflammatory cytokines from the hydrogel-nanoparticle system suggests this could be a highly effective topical therapy. The 120-hour sustained release means less frequent application, improving patient compliance.","specificNumbers":"","methodology":"YARA cell-penetrating MK2 inhibitor peptide was loaded into hollow thermo-responsive pNIPAM nanoparticles, which were then incorporated into chitosan hydrogels. Nanoparticle loading efficiency and hydrogel morphology were characterized. Drug release kinetics were measured over 120 hours. Skin penetration was assessed using porcine skin in Franz diffusion cells under intact and impaired barrier conditions. Anti-inflammatory activity was tested in human keratinocytes under inflammatory conditions and in an ex vivo porcine skin culture model with induced inflammation. Cytokine levels (IL-1β, IL-6, TNF-α) were quantified.","limitations":"All experiments used in vitro cell cultures and ex vivo porcine skin, which may not fully replicate the complex inflammatory environment of human eczema. The study did not test in vivo efficacy in animal eczema models. Porcine skin, while the best non-human model, differs from human skin in thickness and immune composition. Long-term safety of repeated peptide application to damaged skin was not assessed. Manufacturing scalability and cost of the nanoparticle-hydrogel system were not addressed. The YARA peptide sequence is a research tool and would require clinical-grade manufacturing for human use."},{"rthcId":"RPEP-06823","title":"Dulaglutide impedes depressive-like behavior persuaded by chronic social defeat stress model in male C57BL/6 mice: Implications on GLP-1R and cAMP/PKA signaling pathway in the hippocampus.","authors":"Darwish, Amal B; El Sayed, Nesrine S; Salama, Abeer A A; Saad, Muhammed A","year":2023,"journal":"Life sciences, 320, 121546","doi":"10.1016/j.lfs.2023.121546","pmid":"36878280","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Dulaglutide treatment reversed depressive behaviors and improved social interaction in stressed mice.","whyItMatters":"This research highlights the potential of repurposing diabetes medications like dulaglutide for treating depression, which could lead to new therapeutic options.","specificNumbers":"","methodology":"Eighty male C57BL/6 mice were divided into groups with and without chronic social defeat stress, and treated with either saline or dulaglutide over a period of 42 days.","limitations":"The study was conducted in mice, so results may not directly translate to humans. Additionally, the sample size, while adequate for preliminary findings, may limit broader applicability."},{"rthcId":"RPEP-06824","title":"Carcinoid Heart Disease Management: A Multi-Disciplinary Collaboration.","authors":"Das, Satya; Stockton, Shannon S; Hassan, Saamir A","year":2023,"journal":"The oncologist, 28(7), 575-583","doi":"10.1093/oncolo/oyad126","pmid":"37209415","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"25%-65% of patients with carcinoid syndrome develop carcinoid heart disease.","whyItMatters":"Improving adherence to management guidelines can enhance patient outcomes and reduce morbidity and mortality associated with CaHD.","specificNumbers":"","methodology":"The article reviews existing guidelines and emphasizes the need for early screening and multidisciplinary collaboration in managing CaHD.","limitations":"The study primarily focuses on existing guidelines without new experimental data or direct patient outcomes."},{"rthcId":"RPEP-06825","title":"Tirzepatide for the treatment of adults with type 2 diabetes: An endocrine perspective.","authors":"De Block, Christophe; Bailey, Clifford; Wysham, Carol; Hemmingway, Andrea; Allen, Sheryl Elaine; Peleshok, Jennifer","year":2023,"journal":"Diabetes, obesity & metabolism, 25(1), 3-17","doi":"10.1111/dom.14831","pmid":"35929488","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across SURPASS 1–5 trials, tirzepatide (5, 10, 15 mg weekly) produced HbA1c reductions of 1.87–2.59% (20–28 mmol/mol) and body weight reductions of 6.2–12.9 kg. In SURPASS-2, tirzepatide exceeded semaglutide 1 mg on both glycemic and weight outcomes. Additional cardiometabolic benefits included reductions in blood pressure, visceral adiposity, and triglycerides. Safety was similar to the GLP-1 receptor agonist class with low hypoglycemia risk when used without insulin.","whyItMatters":"Tirzepatide represented a paradigm shift when approved — the first drug to target both GIP and GLP-1 receptors simultaneously. Its superior efficacy over semaglutide in head-to-head comparison challenged the notion that single-target GLP-1 drugs were optimal. The magnitude of weight loss (up to 12.9 kg) also blurred the line between diabetes treatment and weight management medication.","specificNumbers":"","methodology":"This is a narrative review summarizing the Phase 3 SURPASS clinical trial program (SURPASS 1–5), which evaluated once-weekly subcutaneous tirzepatide at three doses (5, 10, 15 mg) as monotherapy and combination therapy across diverse type 2 diabetes populations. Comparators included placebo, semaglutide, insulin degludec, and insulin glargine.","limitations":"This is a narrative review, not a systematic review or meta-analysis. The SURPASS trials had relatively short durations for assessing long-term outcomes. Cardiovascular outcome data were not yet available at the time of this review. The semaglutide comparator was the 1 mg dose, not the higher 2.4 mg weight-loss dose. Gastrointestinal side effects, while manageable, remain a consideration."},{"rthcId":"RPEP-06826","title":"Mucosal immune alterations at the early onset of tissue destruction in chronic obstructive pulmonary disease.","authors":"de Fays, Charlotte; Geudens, Vincent; Gyselinck, Iwein; Kerckhof, Pieterjan; Vermaut, Astrid; Goos, Tinne; Vermant, Marie; Beeckmans, Hanne; Kaes, Janne; Van Slambrouck, Jan; Mohamady, Yousry; Willems, Lynn; Aversa, Lucia; Cortesi, Emanuela E; Hooft, Charlotte; Aerts, Gitte; Aelbrecht, Celine; Everaerts, Stephanie; McDonough, John E; De Sadeleer, Laurens J; Gohy, Sophie; Ambroise, Jerome; Janssens, Wim; Ceulemans, Laurens J; Van Raemdonck, Dirk; Vos, Robin; Hackett, Tillie L; Hogg, James C; Kaminski, Naftali; Gayan-Ramirez, Ghislaine; Pilette, Charles; Vanaudenaerde, Bart M","year":2023,"journal":"Frontiers in immunology, 14, 1275845","doi":"10.3389/fimmu.2023.1275845","pmid":"37915582","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In mildly affected COPD zones, decreased defensins and increased mucus were observed alongside CD8+ T cell accumulation.","whyItMatters":"Understanding early immune changes in COPD can help in developing targeted therapies. It highlights the potential for early intervention before severe lung damage occurs.","specificNumbers":"","methodology":"The study analyzed lung tissue from 11 healthy controls and 11 end-stage COPD patients using microCT and RNA transcriptomic analysis.","limitations":"The study is limited by its small sample size and focus on end-stage COPD, which may not represent earlier disease stages."},{"rthcId":"RPEP-06827","title":"Palmitate-Induced Inflammation and Myotube Atrophy in C2C12 Cells Are Prevented by the Whey Bioactive Peptide, Glycomacropeptide.","authors":"de Hart, Naomi Mmp; Petrocelli, Jonathan J; Nicholson, Rebekah J; Yee, Elena M; Ferrara, Patrick J; Bastian, Eric D; Ward, Loren S; Petersen, Brent L; Summers, Scott A; Drummond, Micah J","year":2023,"journal":"The Journal of nutrition, 153(10), 2915-2928","doi":"10.1016/j.tjnut.2023.08.033","pmid":"37652286","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GMP prevented palmitate-induced decrease in myotube area and increased inflammatory gene expression after 24 hours.","whyItMatters":"Understanding how GMP protects muscle cells could lead to new treatments for muscle atrophy associated with metabolic diseases. This research highlights the potential of dietary peptides in managing inflammation and muscle health.","specificNumbers":"","methodology":"C2C12 myoblasts were differentiated and treated with palmitate and GMP to assess effects on muscle atrophy and inflammation over 6-24 hours.","limitations":"The study was conducted in vitro using C2C12 cells, which may not fully replicate human muscle responses."},{"rthcId":"RPEP-06828","title":"Cell-Penetrating Peptides as Valuable Tools for Nose-to-Brain Delivery of Biological Drugs.","authors":"De Martini, Lisa Benedetta; Sulmona, Claudia; Brambilla, Liliana; Rossi, Daniela","year":2023,"journal":"Cells, 12(12)","doi":"10.3390/cells12121643","pmid":"37371113","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CPPs can enhance the delivery of biologics to the brain, overcoming barriers like the blood-brain barrier.","whyItMatters":"Improving drug delivery to the brain could lead to more effective treatments for neurological conditions. Non-invasive methods like intranasal delivery are crucial for patient compliance and safety.","specificNumbers":"","methodology":"The review analyzes various studies on the use of CPPs for nose-to-brain drug delivery.","limitations":"The review does not provide new experimental data and focuses on previously published studies, which may vary in quality."},{"rthcId":"RPEP-06829","title":"Efficacy and safety of the dual GIP and GLP-1 receptor agonist tirzepatide for weight loss: a meta-analysis of randomized controlled trials.","authors":"de Mesquita, Yasmin Luz Lima; Pera Calvi, Izabela; Reis Marques, Isabela; Almeida Cruz, Sara; Padrao, Eduardo Messias Hirano; Carvalho, Pedro Emanuel de Paula; da Silva, Caroliny Hellen Azevedo; Cardoso, Rhanderson; Moura, Filipe Azevedo; Rafalskiy, Vladimir Vitalievich","year":2023,"journal":"International journal of obesity (2005), 47(10), 883-892","doi":"10.1038/s41366-023-01337-x","pmid":"37460681","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 6 RCTs with 4,036 participants (12-72 weeks):\n\n**Weight loss vs placebo:**\n- Tirzepatide 5 mg: -7.7 kg (-8.1%)\n- Tirzepatide 10 mg: -11.6 kg (-11.9%)\n- Tirzepatide 15 mg: -11.8 kg (-12.4%)\n- All doses: p<0.001\n\nTirzepatide also significantly reduced BMI and waist circumference.\n\n**Side effects at 15 mg vs placebo:**\n- Nausea: OR 4.2 (4.2× more likely)\n- Vomiting: OR 7.0 (7× more likely)\n- Diarrhea: OR 2.8 (2.8× more likely)\n\nAll three doses showed a clear dose-response relationship for both efficacy and side effects.","whyItMatters":"This meta-analysis quantifies what individual trials suggested: tirzepatide produces weight loss that rivals bariatric surgery for some patients. The 12.4% body weight reduction at the highest dose exceeds what earlier GLP-1-only drugs achieved, validating the dual-receptor approach. These numbers helped establish tirzepatide as a leading option for medically managed weight loss.","specificNumbers":"","methodology":"Systematic review and meta-analysis searching PubMed, Embase, and Cochrane for randomized controlled trials comparing tirzepatide to placebo. Six studies with 4,036 participants were included, ranging from 12 to 72 weeks. Mean differences were calculated for continuous outcomes and odds ratios for binary outcomes. Risk of bias was assessed using the Cochrane RoB-2 tool. Registered in PROSPERO (CRD42022348576).","limitations":"Only 6 trials were available for analysis, limiting the statistical robustness for subgroup analyses. Trial durations varied from 12 to 72 weeks, and the pooled analysis may not fully account for duration-dependent effects. Long-term weight loss maintenance and safety beyond 72 weeks were not assessed. The gastrointestinal side effect rates may discourage some patients from continuing treatment. Most trials included diabetes patients, so results may not perfectly extrapolate to all obese populations."},{"rthcId":"RPEP-06830","title":"Beauveria bassiana interacts with gut and hemocytes to manipulate Aedes aegypti immunity.","authors":"de Oliveira Barbosa Bitencourt, Ricardo; Corrêa, Thaís Almeida; Santos-Mallet, Jacenir; Santos, Huarrisson Azevedo; Lowenberger, Carl; Moreira, Haika Victória Sales; Gôlo, Patrícia Silva; Bittencourt, Vânia Rita Elias Pinheiro; da Costa Angelo, Isabele","year":2023,"journal":"Parasites & vectors, 16(1), 17","doi":"10.1186/s13071-023-05655-x","pmid":"36650591","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"B. bassiana reduced total hemocyte concentration and altered immune responses in Aedes aegypti larvae.","whyItMatters":"Understanding how this fungus manipulates mosquito immunity could lead to new, effective bioinsecticides, reducing reliance on chemical pesticides.","specificNumbers":"","methodology":"The study involved exposing mosquito larvae to the fungus and assessing immune response changes through microscopy and biochemical assays over 24 and 48 hours.","limitations":"The study focuses only on larvae and may not fully represent adult mosquito responses; further research is needed to confirm findings in different life stages."},{"rthcId":"RPEP-06831","title":"Difficulties in Establishing the Adverse Effects of β-Casomorphin-7 Released from β-Casein Variants-A Review.","authors":"de Vasconcelos, Marta Liliane; Oliveira, Luisa Maria F S; Hill, Jeremy Paul; Vidal, Ana Maria Centola","year":2023,"journal":"Foods (Basel, Switzerland), 12(17)","doi":"10.3390/foods12173151","pmid":"37685085","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06832","title":"Evaluation of tributyrin supplementation in milk replacer on diarrhoea occurrence in preweaning Holstein calves.","authors":"Dell'Anno, Matteo; Scaglia, Elena; Reggi, Serena; Grossi, Silvia; Sgoifo Rossi, Carlo Angelo; Frazzini, Sara; Caprarulo, Valentina; Rossi, Luciana","year":2023,"journal":"Animal : an international journal of animal bioscience, 17(5), 100791","doi":"10.1016/j.animal.2023.100791","pmid":"37121158","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Diarrhea frequency was significantly lower in the tributyrin group (27.91%) compared to the control group (38.37%; P < 0.01).","whyItMatters":"Reducing diarrhea in calves is crucial for improving animal health and reducing economic losses in the cattle industry. This study offers a potential alternative to antibiotics, aligning with efforts to combat antimicrobial resistance.","specificNumbers":"","methodology":"Twelve newborn calves were divided into two groups: one received standard milk replacer, and the other received milk replacer supplemented with 0.3% tributyrin for 42 days. Various health metrics were recorded, including weight, feed intake, and fecal consistency.","limitations":"The study involved a small sample size of only 12 calves, which may limit the generalizability of the results."},{"rthcId":"RPEP-06833","title":"Dulaglutide Protects Mice against Diabetic Sarcopenia-Mediated Muscle Injury by Inhibiting Inflammation and Regulating the Differentiation of Myoblasts.","authors":"Deng, Fengyi; Wu, Wenyan; Fan, Xingyu; Zhong, Xing; Wang, Nuojin; Wang, Yue; Pan, Tianrong; Du, Yijun","year":2023,"journal":"International journal of endocrinology, 2023, 9926462","doi":"10.1155/2023/9926462","pmid":"37584041","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Dulaglutide reduced inflammatory factors and improved muscle tissue health in db/db mice.","whyItMatters":"Understanding how dulaglutide works could lead to new treatments for diabetic sarcopenia, improving quality of life for those with diabetes.","specificNumbers":"","methodology":"The study involved injecting db/db mice with dulaglutide and evaluating muscle tissues for inflammation and differentiation markers.","limitations":"The study was conducted in mice, and results may not directly translate to humans."},{"rthcId":"RPEP-06834","title":"Comparative effectiveness of multiple different treatment regimens for nonalcoholic fatty liver disease with type 2 diabetes mellitus: a systematic review and Bayesian network meta-analysis of randomised controlled trials.","authors":"Deng, Manjun; Wen, Yonghao; Yan, JingXin; Fan, Yichen; Wang, Zhixin; Zhang, Ruixia; Ren, Li; Ba, Yinggui; Wang, Haijiu; Lu, Qian; Fan, Haining","year":2023,"journal":"BMC medicine, 21(1), 447","doi":"10.1186/s12916-023-03129-6","pmid":"37974258","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Exenatide reduced HbA1c by 0.32 and BMI by 0.81 compared to liraglutide.","whyItMatters":"Understanding effective treatments for NAFLD in T2DM patients can guide clinical practice and improve patient outcomes. Identifying effective interventions is crucial given the rising prevalence of these conditions.","specificNumbers":"","methodology":"The study conducted a systematic review and Bayesian network meta-analysis of randomized controlled trials, analyzing data from multiple databases.","limitations":"The evidence was assessed as low certainty, and the study did not evaluate long-term outcomes or the effectiveness of all interventions."},{"rthcId":"RPEP-06835","title":"The Potent Antitumor Activity of Smp43 against Non-Small-Cell Lung Cancer A549 Cells via Inducing Membranolysis and Mitochondrial Dysfunction.","authors":"Deng, Ze; Gao, Yahua; Nguyen, Tienthanh; Chai, Jinwei; Wu, Jiena; Li, Jiali; Abdel-Rahman, Mohamed A; Xu, Xueqing; Chen, Xin","year":2023,"journal":"Toxins, 15(5)","doi":"10.3390/toxins15050347","pmid":"37235381","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Smp43 has an IC50 value of 2.58 μM against A549 cells, indicating potent cytotoxicity.","whyItMatters":"The findings highlight the potential of scorpion venom peptides as novel cancer therapies, particularly for hard-to-treat lung cancers. Understanding how Smp43 works could lead to new treatment strategies.","specificNumbers":"","methodology":"The study assessed the cytotoxic effects of Smp43 on A549 cells in vitro and evaluated its protective effects in xenograft mice models.","limitations":"The study primarily focused on in vitro results, and further research is needed to confirm efficacy and safety in humans."},{"rthcId":"RPEP-06836","title":"Neuroprotective Peptides and New Strategies for Ischemic Stroke Drug Discoveries.","authors":"Dergunova, Lyudmila V; Filippenkov, Ivan B; Limborska, Svetlana A; Myasoedov, Nikolay F","year":2023,"journal":"Genes, 14(5)","doi":"10.3390/genes14050953","pmid":"37239313","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06837","title":"Initial Pharmacological Characterization of a Major Hydroxy Metabolite of PF-5190457: Inverse Agonist Activity of PF-6870961 at the Ghrelin Receptor.","authors":"Deschaine, Sara L; Hedegaard, Morten A; Pince, Claire L; Farokhnia, Mehdi; Moose, Jacob E; Stock, Ingrid A; Adusumalli, Sravani; Akhlaghi, Fatemeh; Hougland, James L; Sulima, Agnieszka; Rice, Kenner C; Koob, George F; Vendruscolo, Leandro F; Holst, Birgitte; Leggio, Lorenzo","year":2023,"journal":"The Journal of pharmacology and experimental therapeutics, 386(2), 117-128","doi":"10.1124/jpet.122.001393","pmid":"36631279","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"PF-6870961, the major hydroxy metabolite of the ghrelin receptor inverse agonist PF-5190457, demonstrated its own binding affinity and inverse agonist activity at GHSR1a. While it had lower binding affinity and potency for blocking inositol phosphate accumulation compared to the parent compound, it showed increased inhibitory potency at β-arrestin recruitment — a form of biased inverse agonism. Intraperitoneal injection suppressed food intake in both male and female rats under food-restricted and ad libitum conditions. Knockout experiments confirmed these effects were mediated specifically through the ghrelin receptor.","whyItMatters":"Understanding that a drug's metabolite is also pharmacologically active is critical for dosing, safety, and efficacy. The biased inverse agonism of PF-6870961 provides new structure-activity insights that could inform design of improved ghrelin receptor therapeutics for alcohol use disorder and potentially obesity.","specificNumbers":"","methodology":"The study combined high-throughput screening for off-target interactions, in vitro binding and concentration-response assays at GHSR1a, and in vivo food intake studies in male and female rats. GHSR knockout rats were used to confirm receptor specificity of the metabolite's effects.","limitations":"All in vivo experiments were conducted in rats, and the metabolite's effects in humans remain to be characterized. The study focused on food intake as the behavioral readout rather than alcohol consumption, which is the primary clinical target. Pharmacokinetic properties of PF-6870961 in humans are not yet fully established."},{"rthcId":"RPEP-06838","title":"Deciphering variations in the endocytic uptake of a cell-penetrating peptide: the crucial role of cell culture protocols.","authors":"Diaz, Joshua; Pellois, Jean-Philippe","year":2023,"journal":"Cytotechnology, 75(6), 473-490","doi":"10.1007/s10616-023-00591-1","pmid":"37841959","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Different cell culture protocols resulted in over 13-fold variations in TMR-TAT uptake.","whyItMatters":"Understanding how cell culture methods affect peptide delivery can lead to more effective therapies using CPPs. This research may help improve drug delivery systems in medical applications.","specificNumbers":"","methodology":"The study systematically compared various cell culture protocols to assess their impact on the endocytic uptake of TMR-TAT peptide.","limitations":"The study focused on a single CPP and specific cell culture conditions, limiting generalizability to other peptides or cell types."},{"rthcId":"RPEP-06839","title":"Elucidating the Impact of Payload Conjugation on the Cell-Penetrating Efficiency of the Endosomal Escape Peptide dfTAT: Implications for Future Designs for CPP-Based Delivery Systems.","authors":"Diaz, Joshua; Pietsch, Miles; Davila, Marissa; Jaimes, Gerardo; Hudson, Alexis; Pellois, Jean-Philippe","year":2023,"journal":"Bioconjugate chemistry, 34(10), 1861-1872","doi":"10.1021/acs.bioconjchem.3c00369","pmid":"37774419","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Larger payloads reduce dfTAT's endocytic uptake and endosomal escape efficiency.","whyItMatters":"Understanding how payload size impacts peptide delivery can lead to improved drug delivery systems. This knowledge is crucial for developing therapies that rely on cell-penetrating peptides.","specificNumbers":"","methodology":"The study systematically examined the effects of various payload sizes on the cell-penetrating activity of the dfTAT peptide.","limitations":"The study primarily focuses on one peptide and may not generalize to all cell-penetrating peptides or payloads."},{"rthcId":"RPEP-06840","title":"Carrier peptide interactions with liposome membranes induce reversible clustering by surface adsorption and shape deformation.","authors":"Diedrichsen, Ragna Guldsmed; Vetri, Valeria; Prévost, Sylvain; Foderà, Vito; Nielsen, Hanne Mørck","year":2023,"journal":"Journal of colloid and interface science, 650(Pt B), 1821-1832","doi":"10.1016/j.jcis.2023.07.078","pmid":"37515972","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"All three cell-penetrating peptides — penetratin, shuffle, and penetramax — adsorbed to lipid bilayer surfaces and induced liposome clustering at specific peptide-to-lipid ratios. However, the nature of their interactions differed significantly: penetratin caused irreversible clustering, penetramax caused partly reversible clustering, and shuffle caused fully reversible clustering.\n\nShuffle and penetramax additionally caused liposome shape deformation, while penetratin did not. Importantly, none of the peptides disrupted liposome integrity under any tested conditions, meaning they interact with membranes without destroying them — a critical requirement for safe drug delivery applications.","whyItMatters":"Oral delivery of peptide drugs like insulin could eliminate the need for daily injections for millions of diabetes patients. Understanding exactly how carrier peptides interact with gut cell membranes — without damaging them — is essential for designing safe and effective oral peptide delivery systems. The reversibility differences between these peptides could influence which is best suited for clinical use.","specificNumbers":"","methodology":"Peptide-liposome interactions were studied using small-angle neutron scattering (SANS) and fluorescence lifetime imaging microscopy (FLIM). Liposomes served as model cell membranes. The three carrier peptides (penetratin, shuffle, and penetramax) were tested at various peptide-to-lipid ratios to characterize membrane adsorption, clustering behavior, reversibility, and structural integrity.","limitations":"Liposomes are simplified models that do not capture the full complexity of living cell membranes, which contain proteins, sugars, and asymmetric lipid compositions. The study did not assess whether the observed membrane interactions translate to actual drug transport across biological barriers. In vivo conditions including enzymes, mucus, and pH changes in the gut were not modeled."},{"rthcId":"RPEP-06841","title":"Treating hepatitis D with bulevirtide - Real-world experience from 114 patients.","authors":"Dietz-Fricke, Christopher; Tacke, Frank; Zöllner, Caroline; Demir, Münevver; Schmidt, Hartmut H; Schramm, Christoph; Willuweit, Katharina; Lange, Christian M; Weber, Sabine; Denk, Gerald; Berg, Christoph P; Grottenthaler, Julia M; Merle, Uta; Olkus, Alexander; Zeuzem, Stefan; Sprinzl, Kathrin; Berg, Thomas; van Bömmel, Florian; Wiegand, Johannes; Herta, Toni; Seufferlein, Thomas; Zizer, Eugen; Dikopoulos, Nektarios; Thimme, Robert; Neumann-Haefelin, Christoph; Galle, Peter R; Sprinzl, Martin; Lohse, Ansgar W; Schulze Zur Wiesch, Julian; Kempski, Jan; Geier, Andreas; Reiter, Florian P; Schlevogt, Bernhard; Gödiker, Juliana; Hofmann, Wolf Peter; Buggisch, Peter; Kahlhöfer, Julia; Port, Kerstin; Maasoumy, Benjamin; Cornberg, Markus; Wedemeyer, Heiner; Deterding, Katja","year":2023,"journal":"JHEP reports : innovation in hepatology, 5(4), 100686","doi":"10.1016/j.jhepr.2023.100686","pmid":"37025462","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06842","title":"The Role of Substance P, Neurokinin A, Neuropeptide Y, and Cortisol in Assessing Neonatal Pain.","authors":"Dionysakopoulou, Christina; Lianou, Loukia; Boutopoulou, Barbara; Giannakopoulou, Margarita; Vlachioti, Efrosini; Koumpagioti, Despoina; Bozas, Evangelos; Matziou, Vasiliki","year":2023,"journal":"Neonatal network : NN, 42(2), 65-71","doi":"10.1891/NN.2022-0006","pmid":"36868802","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Significant decreases in neuropeptide Y (p = 0.02) and neurokinin A (p = 0.03) were observed.","whyItMatters":"Understanding neonatal pain is crucial for improving care in newborns. Identifying reliable biomarkers can lead to better pain management strategies.","specificNumbers":"","methodology":"The study involved 54 full-term neonates and measured biomarker levels alongside two pain assessment scales.","limitations":"The study's sample size was limited to 54 neonates, which may affect the generalizability of the findings."},{"rthcId":"RPEP-06843","title":"Is retatrutide (LY3437943), a GLP-1, GIP, and glucagon receptor agonist a step forward in the treatment of diabetes and obesity?","authors":"Doggrell, Sheila A","year":2023,"journal":"Expert opinion on investigational drugs, 32(5), 355-359","doi":"10.1080/13543784.2023.2206560","pmid":"37086147","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Retatrutide may reduce plasma glucose and body weight more effectively than dulaglutide.","whyItMatters":"With high mortality rates in diabetes, new treatments like retatrutide could significantly improve patient outcomes. Understanding its safety and efficacy is crucial for developing better therapies.","specificNumbers":"","methodology":"The study was a multiple-ascending dose phase 1b clinical trial involving subjects with type 2 diabetes.","limitations":"The study's small sample size and short duration limit the generalizability of the findings."},{"rthcId":"RPEP-06844","title":"Retatrutide showing promise in obesity (and type 2 diabetes).","authors":"Doggrell, Sheila A","year":2023,"journal":"Expert opinion on investigational drugs, 32(11), 997-1001","doi":"10.1080/13543784.2023.2283020","pmid":"37947489","tags":[],"studyType":"review","evidenceStrength":"moderate","keyFinding":"In a phase 2 clinical trial, retatrutide — the first triple-agonist peptide targeting GLP-1, GIP, and glucagon receptors simultaneously — produced dose-dependent weight loss ranging from 7.2% to approximately 18% over just 24 weeks. These results are remarkable given the short study duration, suggesting even greater weight loss with longer treatment. The most common side effects were gastrointestinal (nausea, diarrhea, vomiting), consistent with GLP-1 receptor agonism.\n\nThe author notes a concern: retatrutide increased heart rate by up to 6.7 beats per minute, which may partially offset the cardiovascular benefits of weight loss. Critically, no head-to-head comparator trials against semaglutide or tirzepatide are ongoing, which the author views as a significant gap in the drug's development.","whyItMatters":"Retatrutide represents the next frontier in peptide-based obesity treatment — moving from single-agonist (semaglutide/GLP-1) and dual-agonist (tirzepatide/GLP-1+GIP) to triple-agonist therapy. Adding glucagon receptor activation to the mix could enhance weight loss through increased energy expenditure and fat burning, potentially outperforming existing drugs. However, without head-to-head comparisons, its place in the treatment hierarchy relative to semaglutide and tirzepatide remains unclear.","specificNumbers":"Weight loss: -7.2% to -~18% over 24 weeks · Doses: 1 mg to 12 mg · Heart rate increase: up to +6.7 bpm · 3 receptor targets: GLP-1, GIP, glucagon · Most common AEs: nausea, diarrhea, vomiting","methodology":"This is an expert opinion commentary reviewing results from a phase 2 dose-ranging clinical trial of retatrutide (LY3437943) in obesity. The primary endpoint was percentage weight change from baseline to 24 weeks across dose groups.","limitations":"This commentary reviews phase 2 data only — the trial had a relatively short 24-week duration. No head-to-head comparator studies with semaglutide or tirzepatide exist, making it impossible to directly compare efficacy. The heart rate increase raises cardiovascular safety questions requiring long-term monitoring. Phase 3 data and long-term safety outcomes are needed."},{"rthcId":"RPEP-06845","title":"Multiple Bioactivities of Peptides from Hydrolyzed Misgurnus anguillicaudatus.","authors":"Dou, Baojie; Wu, Xudong; Xia, Zihan; Wu, Guanghao; Guo, Quanyou; Lyu, Mingsheng; Wang, Shujun","year":2023,"journal":"Molecules (Basel, Switzerland), 28(6)","doi":"10.3390/molecules28062589","pmid":"36985560","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Six peptides were identified from hydrolyzed loach protein: D-1 (SERDPSNIKWGDAGAQ), D-2 (TVDGPSGKLWR), D-3 (NDHFVKL), D-4 (AFRVPTP), D-5 (DAGAGIAL), and D-6 (VSVVDLTVR). All showed antioxidant activity, with the <3 kDa fraction exhibiting the strongest DPPH, hydroxyl radical, and superoxide radical scavenging ability.\n\nPeptide D-4 showed ACE inhibitory activity with an IC50 of 95.07 μg/mL (0.12 mM), and D-2 also inhibited ACE. For cholesterol reduction, D-2 inhibited pancreatic cholesterol esterase (IC50 3.19 mg/mL, 2.62 mM), with D-3 and D-6 also showing CE inhibitory activity. Molecular docking confirmed these peptides bind to key amino acids in the catalytic domains of both enzymes.","whyItMatters":"Food-derived bioactive peptides are an increasingly important area of functional food research. Finding peptides that simultaneously combat oxidative stress, potentially lower blood pressure (via ACE inhibition), and reduce cholesterol absorption from a common food fish provides a natural, food-based approach to cardiovascular health. These peptides could be developed into functional food ingredients or nutraceutical products.","specificNumbers":"","methodology":"Loach fish protein was hydrolyzed using alkaline protease, and the hydrolysate was separated by membrane filtration into fractions of different molecular weights. The <3 kDa fraction showing the highest antioxidant activity was further purified by gel filtration chromatography. Peptide sequences were identified using LC-MS/MS. Bioactivities were assessed through in vitro antioxidant assays (DPPH, hydroxyl radical, superoxide radical scavenging, reducing power), ACE inhibition assay, and pancreatic cholesterol esterase inhibition assay. Molecular docking was used to investigate binding mechanisms.","limitations":"All bioactivity testing was performed in vitro (test tube), which does not guarantee these peptides would survive digestion, be absorbed, or remain active in the human body. The ACE and CE inhibition IC50 values, particularly for CE, are relatively high, suggesting modest potency. The molecular docking provides predicted binding mechanisms but not experimental proof. No animal or human studies were conducted. The peptide yields and practical feasibility of large-scale production were not assessed."},{"rthcId":"RPEP-06846","title":"A technology evaluation of the atypical use of a CPP-containing peptide in the formulation and performance of a clinical botulinum toxin product.","authors":"Dowdy, Steven F; Gallagher, Conor J; Vitarella, Domenico; Brown, Jessica","year":2023,"journal":"Expert opinion on drug delivery, 20(9), 1157-1166","doi":"10.1080/17425247.2023.2251399","pmid":"37847051","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"RTP004 enhances presynaptic binding and reduces post-injection diffusion of botulinum toxin.","whyItMatters":"This research represents a breakthrough in drug delivery systems, potentially improving the efficacy of botulinum toxin treatments. The approval of RTP004-containing products could lead to better therapeutic outcomes in clinical settings.","specificNumbers":"","methodology":"The study discusses the formulation characteristics and pharmacological properties of RTP004 in relation to botulinum toxin.","limitations":"The study primarily focuses on the formulation and does not provide extensive clinical trial data on efficacy and safety."},{"rthcId":"RPEP-06847","title":"TAT decorated siRNA polyplexes for inhalation delivery in anti-asthma therapy.","authors":"Drago, Salvatore Emanuele; Cabibbo, Marta; Craparo, Emanuela Fabiola; Cavallaro, Gennara","year":2023,"journal":"European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 190, 106580","doi":"10.1016/j.ejps.2023.106580","pmid":"37717668","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The researchers created polyplexes (polymer-siRNA complexes) using a newly designed copolymer (PHEA-bAPAE-PEG-MLB) and decorated their surface with thiolated TAT peptide via thiol-ene chemistry. The TAT-decorated polyplexes demonstrated several key properties:\n\nThey maintained siRNA binding during mucus diffusion, passed through the mucin layer efficiently despite only forming weak bonds with mucin chains, and were highly cytocompatible (non-toxic to cells). In cellular uptake studies, the polyplexes effectively penetrated into the cytoplasm of bronchial epithelial cells and reduced IL-8 gene expression after LPS-induced inflammation. The final formulation was converted into an inhalable dry powder by encapsulating the polyplexes in mannitol-based microparticles via spray freeze drying, producing highly porous particles with suitable aerodynamic properties for lung delivery.","whyItMatters":"Current asthma treatments primarily manage symptoms rather than targeting the underlying inflammatory gene expression. Inhaled siRNA therapy could silence specific genes driving inflammation, but the lung's mucus barrier makes delivery extremely challenging. Using TAT peptide as a cell-penetrating agent to overcome this barrier represents a creative approach that could open the door to gene-level asthma treatments delivered conveniently as dry powder inhalers.","specificNumbers":"","methodology":"The study involved multi-step polymer synthesis: first creating a protonable copolymer from PHEA backbone with amine and PEG modifications, then complexing it with siRNA to form nanosized polyplexes, and finally decorating them with thiolated TAT peptide. Testing included mucus diffusion assays, cytocompatibility studies, cellular uptake imaging in bronchial epithelial cells, IL-8 gene expression measurement after LPS stimulation, and spray freeze drying to create inhalable microparticles. All experiments were conducted in vitro.","limitations":"All experiments were conducted in vitro — no animal studies or human testing was performed. Mucus diffusion was tested with purified mucin rather than native airway mucus, which is more complex. IL-8 knockdown was demonstrated after artificial LPS stimulation, which may not fully replicate asthma pathophysiology. The aerodynamic performance of the microparticles was characterized technically but not tested in an actual inhalation model."},{"rthcId":"RPEP-06848","title":"The expanding incretin universe: from basic biology to clinical translation.","authors":"Drucker, Daniel J; Holst, Jens J","year":2023,"journal":"Diabetologia, 66(10), 1765-1779","doi":"10.1007/s00125-023-05906-7","pmid":"36976349","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06849","title":"New insights into the bioaccessibility and metabolic fates of short-chain bioactive peptides in goat milk using the INFOGEST static digestion model and an improved data acquisition strategy.","authors":"Du, An; Jia, Wei","year":2023,"journal":"Food research international (Ottawa, Ont.), 169, 112948","doi":"10.1016/j.foodres.2023.112948","pmid":"37254372","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Identified 127 short-chain peptides with concentrations ranging from 0.01 to 27.84 mg L-1.","whyItMatters":"Understanding the digestion of these peptides can help in developing functional foods with health benefits. This research provides insights into how food-derived peptides can be bioaccessible and beneficial.","specificNumbers":"","methodology":"The study employed an in vitro digestion model and advanced mass spectrometry techniques to profile peptides.","limitations":"The study was conducted in vitro, so results may not fully translate to human digestion."},{"rthcId":"RPEP-06850","title":"Identification and molecular interactions of novel ACE inhibitory peptides from rapeseed protein.","authors":"Duan, Xiaojie; Dong, Yifan; Zhang, Min; Li, Zihui; Bu, Guanhao; Chen, Fusheng","year":2023,"journal":"Food chemistry, 422, 136085","doi":"10.1016/j.foodchem.2023.136085","pmid":"37141758","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The peptides FQW, FRW, and CPF showed IC50 values of 44.84 μM, 46.30 μM, and 131.35 μM, respectively.","whyItMatters":"Identifying natural ACE inhibitors can lead to new dietary strategies for managing blood pressure. This research highlights the potential of plant-based proteins in health applications.","specificNumbers":"","methodology":"The study utilized bioinformatics tools to analyze rapeseed proteins and conducted in vitro tests to evaluate ACE inhibitory activity.","limitations":"The study was conducted in vitro, and results may not directly translate to human health outcomes."},{"rthcId":"RPEP-06851","title":"Synthetic growth hormone-releasing hormone agonist ameliorates the myocardial pathophysiology characteristic of heart failure with preserved ejection fraction.","authors":"Dulce, Raul A; Kanashiro-Takeuchi, Rosemeire M; Takeuchi, Lauro M; Salerno, Alessandro G; Wanschel, Amarylis C B A; Kulandavelu, Shathiyah; Balkan, Wayne; Zuttion, Marilia S S R; Cai, Renzhi; Schally, Andrew V; Hare, Joshua M","year":2023,"journal":"Cardiovascular research, 118(18), 3586-3601","doi":"10.1093/cvr/cvac098","pmid":"35704032","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The GHRH agonist MR-356 prevented and reversed diastolic dysfunction and fibrosis in mice.","whyItMatters":"Heart failure with preserved ejection fraction is increasingly common, yet effective treatments are limited. This research offers a potential new therapeutic target.","specificNumbers":"","methodology":"CD1 mice were infused with angiotensin-II to induce HFpEF features, then treated with the GHRH agonist MR-356 for 4 weeks.","limitations":"The study was conducted in mice, and results may not directly translate to humans."},{"rthcId":"RPEP-06852","title":"Role of Novel Glucagon-like Peptide-1 Receptor Analogue Polyethylene Glycol Loxenatide in Type 2 Diabetes: A Systematic Review and Meta-analysis.","authors":"Dutta, Deep; Chatterjee, Subhankar; Datta, Priyankar K; Mohindra, Ritin; Sharma, Meha","year":2023,"journal":"Indian journal of endocrinology and metabolism, 27(5), 377-386","doi":"10.4103/ijem.ijem_162_23","pmid":"38107730","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Patients receiving standard-dose peg-loxenatide (100 mcg/week) had a 0.95% reduction in HbA1c compared to placebo.","whyItMatters":"This research highlights a new treatment option for managing type 2 diabetes, potentially improving patient outcomes with fewer side effects.","specificNumbers":"","methodology":"A systematic review and meta-analysis of randomized controlled trials (RCTs) comparing peg-loxenatide to placebo or other diabetes medications.","limitations":"The analysis is based on a limited number of trials, and results may not fully represent long-term effects or diverse populations."},{"rthcId":"RPEP-06853","title":"Liposomes as Carriers of GHK-Cu Tripeptide for Cosmetic Application.","authors":"Dymek, Michał; Olechowska, Karolina; Hąc-Wydro, Katarzyna; Sikora, Elżbieta","year":2023,"journal":"Pharmaceutics, 15(10)","doi":"10.3390/pharmaceutics15102485","pmid":"37896245","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Key results for liposome-delivered GHK-Cu:\n\n- Stable liposomes of approximately 100 nm were produced using both anionic (AL) and cationic (CL) hydrogenated lecithin\n- Cationic liposomes at 25 mg/cm³ hydrated with 0.5 mg/cm³ GHK-Cu achieved the best encapsulation efficiency: 31.7 ± 0.9%\n- Anionic liposomes achieved 20.0 ± 2.8% encapsulation\n- Cationic liposomes had higher bilayer fluidity\n- GHK-Cu inhibited elastase activity by 48.90 ± 2.50%\n- GHK-Cu did not significantly affect tyrosinase activity\n- The 49% elastase inhibition supports skin structural integrity by reducing elastin degradation","whyItMatters":"GHK-Cu is one of the most studied cosmetic peptides, with evidence for stimulating collagen production, wound healing, and anti-aging effects. However, its effectiveness depends on reaching the right skin layers. This study demonstrates that liposome encapsulation can deliver GHK-Cu while preserving its biological activity, and the strong elastase inhibition (49%) provides a specific mechanism for its anti-aging effects — protecting the elastin network that keeps skin firm and resilient.","specificNumbers":"","methodology":"Liposomes were prepared using the thin-film hydration method combined with freeze-thaw cycles and extrusion. Both anionic and cationic formulations were tested with varying lipid content, composition, and GHK-Cu concentrations. Physicochemical properties (size, stability, bilayer fluidity) and peptide encapsulation efficiency were characterized. In vitro enzyme inhibition assays measured tyrosinase and elastase activity.","limitations":"This is entirely an in vitro formulation study — no skin penetration tests, cell culture viability assays, or clinical testing was performed. The 31.7% encapsulation efficiency means most of the GHK-Cu is not captured by the liposomes. The liposome stability over time during storage was not fully characterized. The elastase and tyrosinase assays are simplified models that may not fully represent skin biology. No comparison to free (unencapsulated) GHK-Cu was described in the abstract."},{"rthcId":"RPEP-06854","title":"Release systems based on self-assembling RADA16-I hydrogels with a signal sequence which improves wound healing processes.","authors":"Dzierżyńska, Maria; Sawicka, Justyna; Deptuła, Milena; Sosnowski, Paweł; Sass, Piotr; Peplińska, Barbara; Pietralik-Molińska, Zuzanna; Fularczyk, Martyna; Kasprzykowski, Franciszek; Zieliński, Jacek; Kozak, Maciej; Sachadyn, Paweł; Pikuła, Michał; Rodziewicz-Motowidło, Sylwia","year":2023,"journal":"Scientific reports, 13(1), 6273","doi":"10.1038/s41598-023-33464-w","pmid":"37072464","tags":["wound-healing","drug-delivery"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Researchers created three new peptide hydrogel materials by combining the self-assembling RADA16-I scaffold with biologically active wound-healing peptide motifs (GHK, KGHK, and RDKVYR) connected through an enzyme-cleavable linker (AAPV). The design is smart: when wound-related enzymes (neutrophil elastase) encounter the hydrogel, they cut the linker and release the active healing peptides at the wound site.\n\nThe hybrid materials maintained the same gelling properties as the original RADA16-I scaffold, showed no toxicity to skin cells, and promoted better cell growth than the unmodified gel. In mice with dorsal skin wounds, topical application of RADA-GHK and RADA-KGHK hydrogels improved wound healing as confirmed by histological analysis.","whyItMatters":"Wound healing peptides like GHK are effective but break down quickly, requiring repeated application. This hydrogel system solves that problem by acting as both a protective scaffold for new skin cells and a controlled-release reservoir that only delivers healing peptides when wound-related enzymes are present. This enzyme-triggered release is an elegant design — the gel responds to the wound environment itself.","specificNumbers":"Three hybrid peptide materials (RADA-GHK, RADA-KGHK, RADA-RDKVYR); AAPV elastase-cleavable linker; no cytotoxicity in fibroblasts/keratinocytes; improved cell proliferation vs RADA16-I alone; improved wound healing in mouse dorsal skin model","methodology":"The researchers synthesized three hybrid peptides and characterized them using circular dichroism, thioflavin T assay, transmission electron microscopy, atomic force microscopy, scanning electron cryomicroscopy, and rheological testing. They tested stability in water and plasma, and enzyme susceptibility. Cytotoxicity was assessed on fibroblasts and keratinocytes using XTT and LDH assays. Wound healing was evaluated in a mouse dorsal skin injury model with histological analysis.","limitations":"Wound healing was only demonstrated in a mouse model, and mouse skin heals differently from human skin. The abstract doesn't report specific wound closure rates, healing times, or quantitative comparisons. Only two of the three hybrid peptides (RADA-GHK and RADA-KGHK) were tested in the wound model — RADA-RDKVYR results aren't mentioned for in vivo. Long-term biocompatibility and manufacturing scalability are unknown."},{"rthcId":"RPEP-06855","title":"A Novel Combination Therapy Tβ4/VIP Protects against Hyperglycemia-Induced Changes in Human Corneal Epithelial Cells.","authors":"Ebrahim, Abdul Shukkur; Carion, Thomas W; Ebrahim, Thanzeela; Win, Jeff; Kani, Hussein; Wang, Yuxin; Stambersky, Ashten; Ibrahim, Ahmed S; Sosne, Gabriel; Berger, Elizabeth A","year":2023,"journal":"Biosensors, 13(11)","doi":"10.3390/bios13110974","pmid":"37998149","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tβ4/VIP treatment significantly improved barrier function and cell migration in high glucose conditions.","whyItMatters":"This research offers a potential new treatment for diabetic patients suffering from corneal complications, which currently have limited options. Improving corneal health can enhance overall quality of life for these individuals.","specificNumbers":"","methodology":"The study used electric cell-substrate impedance sensing (ECIS) to monitor barrier function and wound healing in human corneal epithelial cells exposed to normal and high glucose levels with and without Tβ4/VIP treatment.","limitations":"The study was conducted in vitro, so results may not fully translate to human patients. Further research is needed to confirm efficacy in clinical settings."},{"rthcId":"RPEP-06856","title":"Nanoliposomal peptides derived from Spirulina platensis protein accelerate full-thickness wound healing.","authors":"Ebrahimi, Alireza; Reza Farahpour, Mohammad; Amjadi, Sajed; Mohammadi, Maryam; Hamishehkar, Hamed","year":2023,"journal":"International journal of pharmaceutics, 630, 122457","doi":"10.1016/j.ijpharm.2022.122457","pmid":"36455754","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Spirulina protein hydrolysate (SPH)-loaded nanoliposomes (NLPs) were successfully created with a particle size of 158 nm and zeta potential of -48 mV, indicating good stability. Key findings:\n\n**In vitro**: SPH showed no toxicity to human fibroblast cells (HFFF-2) and actually increased cell growth. Scratch wound assays confirmed faster cell migration with SPH treatment.\n\n**In vivo (162 mice, 9 groups)**: The SPH-NLP treated group showed superior results compared to blank gel, blank NLPs, and free SPH groups at all concentrations (2.5%, 5%, 10%):\n- Higher wound contraction rates\n- Increased epithelialization\n- Greater fibroblast proliferation\n- Elevated expression of bFGF (growth factor), CD31 (blood vessel marker), and COL1A (collagen)\n\nThe nanoliposome encapsulation enhanced peptide delivery and efficacy beyond free peptide application.","whyItMatters":"Chronic and slow-healing wounds affect millions of people, particularly those with diabetes or immune disorders. Current wound treatments are limited, and there's growing interest in natural peptide-based therapies. This study shows that spirulina — an inexpensive, widely available algae — can be processed into wound-healing peptides, and that nanoliposome delivery significantly enhances their effectiveness. This could lead to affordable, natural wound care products.","specificNumbers":"","methodology":"The study had three phases: (1) Spirulina protein was hydrolyzed into peptides and encapsulated in nanoliposomes, then characterized for size, charge, and morphology. (2) In vitro safety and efficacy was tested using MTT toxicity assays and scratch wound tests on human fibroblast cells. (3) In vivo wound healing was tested in 162 mice divided into 9 groups (blank gel, blank NLPs, three concentrations of free SPH, three concentrations of SPH-NLPs). Wound healing was assessed by contraction measurements, histopathology, and immunofluorescence staining for bFGF, CD31, and COL1A.","limitations":"The study was conducted in mice, and wound healing differs significantly between rodents and humans — mice heal primarily by contraction, while humans rely more on re-epithelialization. The specific peptide sequences responsible for the healing effect were not identified. The optimal dose and application frequency for human wounds are unknown. Long-term safety of repeated nanoliposome application to wounds was not assessed. The study did not compare against established wound healing treatments."},{"rthcId":"RPEP-06857","title":"The In Vitro Pro-inflammatory Functions of the SP/NK1R System in Prostate Cancer: a Focus on Nuclear Factor-Kappa B (NF-κB) and Its Pro-inflammatory Target Genes.","authors":"Ebrahimi, Safieh; Erfani, Bahareh; Alalikhan, Abbas; Ghorbani, Hamidreza; Farzadnia, Mahdi; Afshari, Amir R; Mashkani, BaratAli; Hashemy, Seyed Isaac","year":2023,"journal":"Applied biochemistry and biotechnology, 195(12), 7796-7807","doi":"10.1007/s12010-023-04495-w","pmid":"37093533","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"SP increased pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and NF-κB levels, while aprepitant reduced these effects.","whyItMatters":"Understanding the role of inflammation in prostate cancer could lead to new treatment strategies. Aprepitant's potential as an anti-inflammatory agent may improve cancer management.","specificNumbers":"","methodology":"The study used MTT assays for cytotoxicity, Western blot for protein expression, and qRT-PCR for mRNA levels of cytokines.","limitations":"The study was conducted in vitro, so results may not directly translate to human patients. Further research is needed to confirm findings in vivo."},{"rthcId":"RPEP-06858","title":"Application of Topical Sandalore® Increases Epidermal Dermcidin Synthesis in Organ-Cultured Human Skin ex vivo.","authors":"Edelkamp, Janin; Lousada, Marta B; Pinto, Daniela; Chéret, Jérémy; O'Sullivan, James D B; Biundo, Antonio; Jimenez, Francisco; Funk, Wolfgang; Roessing, Christian; Rippmann, Volker; Paus, Ralf; Bertolini, Marta","year":2023,"journal":"Skin pharmacology and physiology, 36(3), 117-124","doi":"10.1159/000528402","pmid":"36702115","tags":["antimicrobial-peptides","skin"],"studyType":"ex-vivo","evidenceStrength":"preliminary","keyFinding":"Applying Sandalore® (a synthetic sandalwood-scented compound) to organ-cultured human skin activated an olfactory receptor (OR2AT4) in epidermal cells, causing them to produce and secrete more dermcidin — an antimicrobial peptide. This was the first demonstration that epidermal keratinocytes can produce dermcidin (previously thought to come only from sweat glands). LL-37 (cathelicidin) expression was not affected.\n\nThe dermcidin-enriched culture medium selectively inhibited Staphylococcus aureus growth while promoting the growth of beneficial skin bacteria (S. epidermidis) and the commensal fungus Malassezia restricta. This suggests Sandalore® could reshape the skin microbiome by boosting the skin's natural antimicrobial defenses.","whyItMatters":"Skin conditions like atopic dermatitis (eczema) and seborrheic dermatitis are driven by overgrowth of S. aureus and Malassezia on the skin. If a simple topical fragrance compound can selectively boost antimicrobial peptide production and shift the skin microbiome toward a healthier balance, it could become an inexpensive, drug-free adjunct treatment for these common conditions.","specificNumbers":"OR2AT4 receptor activated · Dermcidin (DCD) increased · LL-37 unaffected · S. aureus inhibited · S. epidermidis promoted · Malassezia restricta promoted · C. acnes minimally affected","methodology":"Ex vivo pilot study using organ-cultured human skin. Sandalore® was applied topically to skin samples cultured with antibiotics. Researchers measured OR2AT4 protein expression, dermcidin-positive cells, and dermcidin secretion using immunohistomorphometry and ELISA. Culture medium from treated skin was tested against bacterial (S. aureus, S. epidermidis, C. acnes) and fungal (M. restricta) strains using spectrophotometric assays.","limitations":"This is an ex vivo pilot study — human skin was cultured in a lab, not treated on living patients. The sample sizes are not specified and are likely very small. The results need confirmation in vivo, where factors like sweat, sebum, UV exposure, and the existing microbiome would all influence outcomes. Sandalore® is a commercial fragrance compound, and its safety profile for therapeutic skin applications needs further evaluation."},{"rthcId":"RPEP-06859","title":"Improved health-related quality of life during peptide receptor radionuclide therapy in patients with neuroendocrine tumours.","authors":"Edfeldt, Katarina; Hellman, Per; Granberg, Dan; Lagergren, Pernilla; Thiis-Evensen, Espen; Sundin, Anders; Andersson, Camilla","year":2023,"journal":"Journal of neuroendocrinology, 35(10), e13342","doi":"10.1111/jne.13342","pmid":"37807573","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"HRQoL improved in global quality of life, role, social, and emotional functioning.","whyItMatters":"Improving HRQoL is crucial for cancer patients, as it directly impacts their overall well-being and treatment satisfaction. These findings can guide personalized care approaches.","specificNumbers":"","methodology":"The study involved 204 NET patients who completed HRQoL questionnaires before and after up to four cycles of PRRT, with results compared to a reference population.","limitations":"The study may not account for all variables affecting HRQoL and was limited to a specific patient population."},{"rthcId":"RPEP-06860","title":"Deciphering Structural Determinants Distinguishing Active from Inactive Cell-Penetrating Peptides for Cytosolic mRNA Delivery.","authors":"Egberink, Rik Oude; van Asbeck, Alexander H; Boswinkel, Milou; Muradjan, Grigor; Dieker, Jürgen; Brock, Roland","year":2023,"journal":"Bioconjugate chemistry, 34(10), 1822-1834","doi":"10.1021/acs.bioconjchem.3c00346","pmid":"37733627","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Systematic engineering of a human lactoferrin-derived CPP revealed that amphipathic sequence motifs are the critical structural determinant for cytosolic mRNA delivery.\n\nNeither histidine incorporation (to promote the proton sponge effect for endosomal escape), nor arginine-to-lysine/ornithine substitutions, nor disulfide-mediated oligomerization were sufficient to convert an uptake-only CPP into a delivery-active one — despite all modified peptides showing cellular uptake. Only the transfer of amphipathic motifs from the delivery-active PepFect14 achieved functional mRNA delivery, with some additional benefit from oligomerization.","whyItMatters":"mRNA therapeutics — including vaccines and gene therapies — depend on getting mRNA past cell membranes and out of endosomes. Cell-penetrating peptides are a promising delivery vehicle, but the field has lacked clear rules for what makes a CPP effective. This study identifies amphipathic structure as the key requirement, providing a design principle that could guide development of more effective peptide-based delivery systems.","specificNumbers":"","methodology":"Researchers started with a human lactoferrin-derived CPP that enters cells but cannot deliver cargo to the cytosol. They systematically incorporated structural modifications: histidine residues (to test proton sponge effects), amino acid substitutions mimicking PepFect14, and disulfide-mediated polymerization. Each variant was tested for polyplex stability (using heparin displacement assays), cellular uptake, and functional mRNA delivery activity.","limitations":"This is an in vitro cell culture study; in vivo delivery efficiency and biodistribution were not assessed. The findings are primarily based on modifications of one specific CPP scaffold (human lactoferrin), and the design rules may not fully generalize to all CPP families. Functional mRNA delivery was assessed but detailed quantification of delivery efficiency compared to established systems like lipid nanoparticles was not provided."},{"rthcId":"RPEP-06861","title":"Challenges and opportunities in analyzing and modeling peptide presentation by HLA-II proteins.","authors":"ElAbd, Hesham; Bacher, Petra; Tholey, Andreas; Lenz, Tobias L; Franke, Andre","year":2023,"journal":"Frontiers in immunology, 14, 1107266","doi":"10.3389/fimmu.2023.1107266","pmid":"37063883","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Identifying specific peptides presented by HLA proteins can lead to better vaccines and immunotherapies.","whyItMatters":"Understanding how HLA proteins present peptides can significantly impact disease treatment and prevention strategies. It has implications for developing targeted immunotherapies and vaccines.","specificNumbers":"","methodology":"The study is a perspective piece discussing challenges and solutions in peptide presentation analysis.","limitations":"The study is a perspective piece and does not present original experimental data."},{"rthcId":"RPEP-06862","title":"Nationwide cardiovascular risk categorization: applying the European Society of Cardiology guidelines to the Swedish National Diabetes Register.","authors":"Eliasson, Björn; Ekelund, Jan; Holmberg, Cecilia Nagorny; Wolden, Michael Lyng; Matthiessen, Kasper Sommer; James, Stefan","year":2023,"journal":"European journal of preventive cardiology, 30(7), 546-551","doi":"10.1093/eurjpc/zwac308","pmid":"36567502","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"129,512 out of 320,028 patients with type 2 diabetes had very high CVD risk; 803 MACE could have been avoided with semaglutide.","whyItMatters":"This research highlights a gap in treatment for high-risk diabetes patients, which could lead to preventable cardiovascular events. Addressing this gap could significantly improve patient outcomes.","specificNumbers":"","methodology":"The study analyzed data from the Swedish National Diabetes Register, applying ESC guidelines to identify high-risk patients and estimate potential outcomes.","limitations":"The study is observational and relies on existing data, which may not capture all relevant clinical factors or outcomes."},{"rthcId":"RPEP-06863","title":"Addition of Peptide Receptor Radiotherapy to Immune Checkpoint Inhibition Therapy Improves Outcomes in Neuroendocrine Tumors.","authors":"Esfahani, Shadi A; De Aguiar Ferreira, Carolina; Summer, Priska; Mahmood, Umar; Heidari, Pedram","year":2023,"journal":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 64(7), 1056-1061","doi":"10.2967/jnumed.123.265391","pmid":"37024303","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 96 humanized mice with gastroenteropancreatic NETs, the early PRRT group (PRRT on day 0 followed by anti-PD1 on day 3) showed the most significant tumor reduction: 205 mm³ to 78 mm³ over 21 days (p=0.0074). PET/MRI imaging confirmed the strongest T-cell activation in this group, with SUVmax increasing from 0.73 to 3.36 (p<0.05) for granzyme-B uptake — indicating robust cytotoxic T-cell activation. The simultaneous and anti-PD1-first groups showed less tumor growth reduction, and PRRT or anti-PD1 alone were least effective.","whyItMatters":"Neuroendocrine tumors have limited treatment options and often resist immunotherapy. This study reveals that PRRT can 'prime' the immune system — the radiation delivered by the peptide carrier triggers an inflammatory response that makes immunotherapy much more effective. The finding that sequence matters (PRRT first works best) provides a practical framework for designing combination clinical trials.","specificNumbers":"","methodology":"Researchers implanted human QGP-1 neuroendocrine tumor cells into immunodeficient mice engrafted with human immune cells (96 mice total, 12 per group). Six groups received: pembrolizumab alone, [177Lu]DOTATATE PRRT alone, simultaneous treatment, delayed PRRT (anti-PD1 first), early PRRT (PRRT first then anti-PD1), or vehicle control. Granzyme-B-specific PET/MRI tracked T-cell activation before and 6 days after treatment. Response was measured by tumor growth over 21 days and histological analysis.","limitations":"This is a preclinical study using humanized mice, which do not fully replicate the human immune system or tumor microenvironment. The human immune reconstitution model has inherent limitations, including potential graft-versus-host effects. The 21-day follow-up is short and doesn't capture long-term outcomes or potential toxicity. The gastroenteropancreatic NET model may not represent all NET subtypes."},{"rthcId":"RPEP-06864","title":"Immune modulation via dendritic cells by the effect of Thymosin-alpha-1 on immune synapse in HCMV infection.","authors":"Espinar-Buitrago, M S; Vazquez-Alejo, E; Magro-Lopez, E; Tarancon-Diez, L; Leal, M; Muñoz-Fernandez, M A","year":2023,"journal":"International immunopharmacology, 125(Pt A), 111103","doi":"10.1016/j.intimp.2023.111103","pmid":"38149577","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06865","title":"The use of alpha 1 thymosin as an immunomodulator of the response against SARS-Cov2.","authors":"Espinar-Buitrago, M S; Tarancon-Diez, L; Vazquez-Alejo, E; Magro-Lopez, E; Genebat, M; Romero-Candau, F; Leal, M; Muñoz-Fernandez, M A","year":2023,"journal":"Immunity & ageing : I & A, 20(1), 32","doi":"10.1186/s12979-023-00351-x","pmid":"37408063","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06866","title":"Novel antihypertensive peptides from lupin protein hydrolysate: An in-silico identification and molecular docking studies.","authors":"Fadimu, Gbemisola J; Gan, Chee-Yuen; Olalere, Olusegun A; Farahnaky, Asgar; Gill, Harsharn; Truong, Tuyen","year":2023,"journal":"Food chemistry, 407, 135082","doi":"10.1016/j.foodchem.2022.135082","pmid":"36493485","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Lupin protein treated with ultrasound and then enzymatically hydrolyzed produced peptide mixtures with ACE-inhibitory activity. The unfractionated alcalase hydrolysate (IC50 = 3.21 mg/mL) and flavourzyme hydrolysate (IC50 = 3.32 mg/mL) were more potent than their ultrafiltrated fractions (IC50 = 6.09–7.45 mg/mL), suggesting synergistic effects among peptides.\n\nMolecular docking analysis identified six novel peptides as predicted ACE inhibitors: AIPPGIPY, SVPGCT, and QGAGG from the alcalase hydrolysate, and AIPINNPGKL, SGNQGP, and PPGIP from the flavourzyme hydrolysate.","whyItMatters":"High blood pressure affects over a billion people worldwide, and there is growing interest in food-derived bioactive peptides as natural alternatives or supplements to pharmaceutical ACE inhibitors. Identifying specific peptide sequences from lupin protein could lead to functional foods or nutraceuticals for blood pressure management, adding value to an underutilized plant protein source.","specificNumbers":"","methodology":"Lupin protein isolate was pre-treated with ultrasound and then hydrolyzed using two different enzymes (alcalase and flavourzyme). The resulting hydrolysates were fractionated by molecular weight (1, 5, and 10 kDa) using membrane ultrafiltration. ACE-inhibitory activity was measured in vitro. Molecular docking simulations were used to predict which specific peptide sequences in the hydrolysates were most likely responsible for ACE inhibition.","limitations":"This study was entirely in vitro and computational — no animal or human testing was performed. Molecular docking predicts binding potential but does not confirm biological activity. The identified peptides have not been synthesized and tested individually. Whether these peptides survive digestion and reach the bloodstream in active form is unknown. The IC50 values are relatively high compared to pharmaceutical ACE inhibitors."},{"rthcId":"RPEP-06867","title":"Lactobacillus casei-Derived Postbiotics Elevate the Bioaccessibility of Proteins via Allosteric Regulation of Pepsin and Trypsin and Introduction of Endopeptidases.","authors":"Fan, Zibian; Jia, Wei","year":2023,"journal":"Journal of agricultural and food chemistry, 71(28), 10647-10669","doi":"10.1021/acs.jafc.3c02125","pmid":"37410960","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06868","title":"Cooperative assembly of a designer peptide and silk fibroin into hybrid nanofiber gels for neural regeneration after spinal cord injury.","authors":"Feng, Feng; Song, Xiyong; Tan, Zan; Tu, Yujie; Xiao, Longyou; Xie, Pengfei; Ma, Yahao; Sun, Xiumin; Ma, Junwu; Rong, Limin; He, Liumin","year":2023,"journal":"Science advances, 9(25), eadg0234","doi":"10.1126/sciadv.adg0234","pmid":"37352345","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The functional self-assembling peptide (F-SAP) and silk fibroin (SF) cooperatively assembled into a hybrid nanofiber hydrogel through a mechanism driven by osmotic pressure and electrostatic interactions. SF micelles diffused into the F-SAP solution and rearranged into rod-like filaments oriented nearly perpendicular to the peptide nanofibers. Spectroscopy confirmed that SF underwent a structural transition from random coil to β-sheet, which strengthened the gel mechanically.\n\nWhen combined with controlled release of NT-3 (neurotrophin-3), the hybrid gel created a permissive environment for neural regeneration: it provided nanofiber substrates for axon growth, modulated inflammation, and promoted remyelination. This resulted in measurable improvements in locomotion and electrophysiological function. The hydrogel demonstrated potential as a long-term in vivo stent for spinal cord injury treatment.","whyItMatters":"Spinal cord injury remains one of the most intractable problems in medicine — there are no approved treatments that restore function. This study presents a sophisticated biomaterial approach that addresses multiple barriers to recovery simultaneously: structural support, growth factor delivery, inflammation control, and remyelination. Published in Science Advances, it represents a significant advance in peptide-based regenerative medicine.","specificNumbers":"","methodology":"The researchers fabricated the hybrid hydrogel by combining a designer self-assembling peptide (F-SAP) with silk fibroin (SF). The assembly mechanism was characterized using circular dichroism, Raman spectroscopy, and fluorescence spectroscopy to track SF conformational changes. Mechanical properties were tested. NT-3 was loaded for controlled release. The hydrogel was evaluated in a spinal cord injury model, assessing axon regeneration, inflammatory modulation, remyelination, locomotor recovery, and electrophysiological properties.","limitations":"The study appears to be preclinical (the abstract does not specify the animal model, though spinal cord injury models are typically conducted in rats or mice). Long-term outcomes, safety, and biodegradation profiles would need extensive evaluation. Translation to human spinal cord injury — which involves much larger defects and different immune responses — faces significant challenges. Specific quantitative recovery metrics were not detailed in the abstract."},{"rthcId":"RPEP-06869","title":"Expression and functional characterization of three β-defensins in grass carp (Ctenopharyngodon idella).","authors":"Feng, Jianhua; Jia, Zhao; Yuan, Gaoliang; Zhu, Xiaozhen; Liu, Qin; Wu, Kaizheng; Wang, Junya; Zou, Jun","year":2023,"journal":"Developmental and comparative immunology, 140, 104616","doi":"10.1016/j.dci.2022.104616","pmid":"36565823","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06870","title":"Functionalised penetrating peptide-chondroitin sulphate‑gold nanoparticles: Synthesis, characterization, and applications as an anti-Alzheimer's disease drug.","authors":"Feng, Yangjun; Li, Xiaolin; Ji, Dongsheng; Tian, Jialei; Peng, Qian; Shen, Yuzhen; Xiao, Yuliang","year":2023,"journal":"International journal of biological macromolecules, 230, 123125","doi":"10.1016/j.ijbiomac.2022.123125","pmid":"36603725","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06871","title":"Cost-effectiveness analysis of once-daily oral semaglutide versus placebo and subcutaneous glucagon-like peptide-1 receptor agonists added to insulin in patients with type 2 diabetes in China.","authors":"Feng, Zhen; Tong, Wai Kei; Zhang, Xinyue; Tang, Zhijia","year":2023,"journal":"Frontiers in pharmacology, 14, 1226778","doi":"10.3389/fphar.2023.1226778","pmid":"37621313","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06872","title":"Weight-dependent and weight-independent effects of dulaglutide on blood pressure in patients with type 2 diabetes.","authors":"Ferdinand, Keith C; Dunn, Julia; Nicolay, Claudia; Sam, Flora; Blue, Emily K; Wang, Hui","year":2023,"journal":"Cardiovascular diabetology, 22(1), 49","doi":"10.1186/s12933-023-01775-x","pmid":"36894938","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In a meta-analysis of five placebo-controlled trials, dulaglutide 1.5 mg reduced systolic blood pressure by −2.6 mmHg (95% CI: −3.8 to −1.5; p<0.001) compared to placebo. Mediation analysis revealed that 36% of this effect was weight-dependent (−0.9 mmHg) and 64% was weight-independent (−1.5 mmHg).\n\nFor pulse pressure, the total reduction was −2.5 mmHg, with 86% attributable to weight-independent mechanisms. Diastolic blood pressure showed minimal impact, with only a small weight-mediated effect. At the higher 4.5 mg dose, additional SBP and pulse pressure reductions beyond the 1.5 mg dose were primarily weight-mediated.","whyItMatters":"GLP-1 receptor agonists are primarily prescribed for blood sugar control and weight management, but their cardiovascular benefits are increasingly recognized. Understanding that most of dulaglutide's blood pressure effect is independent of weight loss suggests these drugs may have direct vascular or renal mechanisms — which could inform their use as part of comprehensive cardiovascular risk management in diabetes.","specificNumbers":"","methodology":"Mediation analysis was conducted across five randomized, placebo-controlled trials from the AWARD clinical program evaluating dulaglutide 1.5 mg over approximately 6 months. The analysis estimated the proportion of blood pressure change mediated by weight loss versus weight-independent pathways. Results were combined via random-effects meta-analysis. A separate analysis in AWARD-11 compared dulaglutide 4.5 mg vs. 1.5 mg to assess dose-response relationships.","limitations":"The analysis is post-hoc, not a prospectively designed blood pressure trial. The mediation approach cannot definitively establish causation for weight-independent mechanisms. The specific biological pathways underlying the weight-independent effects were not identified. The trials had relatively short durations (~6 months), and long-term blood pressure effects may differ."},{"rthcId":"RPEP-06873","title":"Comparative Analysis of Cyclization Techniques in Stapled Peptides: Structural Insights into Protein-Protein Interactions in a SARS-CoV-2 Spike RBD/hACE2 Model System.","authors":"Ferková, Sára; Froehlich, Ulrike; Nepveu-Traversy, Marie-Édith; Murza, Alexandre; Azad, Taha; Grandbois, Michel; Sarret, Philippe; Lavigne, Pierre; Boudreault, Pierre-Luc","year":2023,"journal":"International journal of molecular sciences, 25(1)","doi":"10.3390/ijms25010166","pmid":"38203338","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06874","title":"Potential and limitations of epitope mapping and molecular targeting in Hymenoptera venom allergy.","authors":"Fernandes, Luís Gustavo Romani; Spillner, Edzard; Jakob, Thilo","year":2023,"journal":"Frontiers in allergy, 4, 1327391","doi":"10.3389/falgy.2023.1327391","pmid":"38162556","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06875","title":"Effectiveness of Calcitonin Gene-Related Peptide Monoclonal Antibodies in the Prevention of Migraine: A Systematic Review and Meta-Analysis of Observational Cohort Studies.","authors":"Ferreira, Vinicius L; Mainka, Felipe F; Wiens, Astrid; Pontarolo, Roberto","year":2023,"journal":"Clinical drug investigation, 43(9), 669-680","doi":"10.1007/s40261-023-01301-7","pmid":"37665501","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 47 observational cohort studies, CGRP monoclonal antibodies showed strong real-world effectiveness for migraine prevention:\n\n- 54% of patients (95% CI 49–59%) achieved at least 50% reduction in monthly migraine days\n- Mean monthly migraine reduction: approximately 7.7 days (95% CI 7.0–8.4)\n- 57% of patients (95% CI 48–64%) achieved at least 50% reduction in monthly headache days\n- Mean monthly headache reduction: approximately 8.8 days (95% CI 7.5–10.1)\n\nSubgroup analyses by specific drug (erenumab, fremanezumab, galcanezumab, eptinezumab) and migraine type showed consistent results.","whyItMatters":"Clinical trials show drugs work under ideal conditions, but real-world effectiveness often falls short. This meta-analysis demonstrates that CGRP antibodies maintain their effectiveness in everyday clinical practice, where patients often have more complex medical histories and different treatment adherence patterns than trial participants. For the millions of migraine sufferers who haven't responded to traditional preventive treatments, this confirms that CGRP antibodies are a genuinely effective option.","specificNumbers":"","methodology":"This was a systematic review and meta-analysis of observational cohort studies. Researchers searched electronic databases for real-world studies evaluating CGRP receptor antagonist antibodies (erenumab, fremanezumab, galcanezumab, eptinezumab) in adult migraine patients. Primary outcomes were mean reduction in monthly migraine/headache days and the proportion of patients achieving at least 50% reduction. Forty-seven studies met inclusion criteria for qualitative and quantitative analysis.","limitations":"Observational studies are inherently subject to selection bias — patients who continue treatment may be the ones responding, inflating effectiveness estimates. There was no placebo comparison group, so the placebo effect and natural regression to the mean cannot be separated from drug effects. Heterogeneity across 47 studies with different methodologies, patient populations, and follow-up durations could affect results. Publication bias may favor positive outcomes. Individual patient data was not available for more granular analysis."},{"rthcId":"RPEP-06876","title":"Sodium is a negative allosteric regulator of the ghrelin receptor.","authors":"Ferré, Guillaume; Gomes, Antoniel A S; Louet, Maxime; Damian, Marjorie; Bisch, Paulo M; Saurel, Olivier; Floquet, Nicolas; Milon, Alain; Banères, Jean-Louis","year":2023,"journal":"Cell reports, 42(4), 112320","doi":"10.1016/j.celrep.2023.112320","pmid":"37027306","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Using a combination of sodium-23 NMR spectroscopy, molecular dynamics simulations, and mutagenesis experiments, researchers demonstrated that sodium ions bind to a conserved allosteric site on the ghrelin receptor (GHSR). This binding shifts the receptor's conformational equilibrium toward its inactive state, decreasing both basal (constitutive) activity and agonist-induced G protein activation.\n\nThe allosteric sodium site is conserved across class A GPCRs, but this study specifically characterized its functional impact on GHSR for the first time, establishing sodium as an integral component of the ghrelin signaling machinery.","whyItMatters":"The ghrelin receptor is a major drug target for appetite disorders, obesity, and growth hormone deficiency. Understanding that sodium naturally regulates this receptor could open new approaches to modulating hunger and metabolism — and may explain why dietary sodium intake affects appetite-related signaling pathways.","specificNumbers":"","methodology":"The researchers used multiple complementary techniques: 23Na-NMR to detect sodium binding to the receptor, molecular dynamics simulations to model sodium-receptor interactions at the atomic level, site-directed mutagenesis to confirm the binding site, and spectroscopic and functional G protein activation assays to measure the downstream effects of sodium binding on receptor activity.","limitations":"The experiments were conducted using purified receptor in controlled laboratory conditions, not in living cells or organisms. The physiological relevance of sodium's allosteric effect on GHSR under normal cellular sodium concentrations remains to be fully validated. The study did not examine whether sodium's effect differs across different ghrelin receptor signaling pathways (biased agonism)."},{"rthcId":"RPEP-06877","title":"Correlations between antimicrobial peptides and spectrophotometric skin color parameters in patients with basal cell carcinoma.","authors":"Fijałkowska, Marta; Koziej, Mateusz; Antoszewski, Bogusław; Sitek, Aneta","year":2023,"journal":"Journal of cancer research and clinical oncology, 149(9), 5697-5704","doi":"10.1007/s00432-022-04530-z","pmid":"36542158","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06878","title":"The role of TGF-β and antimicrobial peptides in basal cell carcinoma: a systematic review.","authors":"Fijałkowska, Marta; Bonczar, Michał; Jastrzębski, Ignacy; Ostrowski, Patryk; Antoszewski, Bogusław; Koziej, Mateusz","year":2023,"journal":"Postepy dermatologii i alergologii, 40(3), 384-389","doi":"10.5114/ada.2023.124747","pmid":"37545828","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06879","title":"Structural Basis for Self-Discrimination by Neoantigen-Specific TCRs.","authors":"Finnigan, John P; Newman, Jenna H; Patskovsky, Yury; Patskovska, Larysa; Ishizuka, Andrew S; Lynn, Geoffrey M; Seder, Robert A; Krogsgaard, Michelle; Bhardwaj, Nina","year":2023,"journal":"Research square","doi":"10.21203/rs.3.rs-2531184/v1","pmid":"36778273","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06880","title":"Mechanisms of action of incretin receptor based dual- and tri-agonists in pancreatic islets.","authors":"Folli, Franco; Finzi, Giovanna; Manfrini, Roberto; Galli, Alessandra; Casiraghi, Francesca; Centofanti, Lucia; Berra, Cesare; Fiorina, Paolo; Davalli, Alberto; La Rosa, Stefano; Perego, Carla; Higgins, Paul B","year":2023,"journal":"American journal of physiology. Endocrinology and metabolism, 325(5), E595-E609","doi":"10.1152/ajpendo.00236.2023","pmid":"37729025","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Clinical studies of dual GLP-1/GIP receptor agonists (unimolecular dual-receptor agonists or UDRAs) have demonstrated favorable results both as standalone treatments and in combination with other diabetes drugs. The additive insulin-boosting effects of dual GLP-1 and GIP receptor activation were expected based on what each hormone does individually.\n\nHowever, the additional benefits from adding glucagon receptor (GCGR) activation in triple agonists were largely unexpected, since glucagon normally raises blood sugar. Whether simultaneous stimulation of these three receptor pathways creates synergistic or antagonistic interactions at the cellular level remains unknown and requires further investigation.","whyItMatters":"Drugs like tirzepatide (a dual GLP-1/GIP agonist) and retatrutide (a triple agonist) represent a major shift in diabetes and obesity treatment. Understanding exactly how these drugs work at the cellular level is essential for predicting long-term safety, optimizing dosing, and designing even better multi-agonist peptides. The finding that glucagon receptor activation provides unexpected benefits challenges conventional thinking about diabetes treatment.","specificNumbers":"","methodology":"This was a scoping review examining the published literature on the cellular mechanisms of action of dual- and triple-receptor agonist peptides in pancreatic islet cells. The authors analyzed studies covering the signaling pathways activated by GLP-1, GIP, and glucagon receptors individually and in combination, drawing on both preclinical mechanistic studies and clinical efficacy trials.","limitations":"As a scoping review, this paper maps the current state of knowledge rather than providing new experimental data. The authors acknowledge that the signaling pathway interactions from simultaneous dual and triple receptor stimulation require much deeper investigation. Most mechanistic understanding comes from studying each receptor pathway individually, which may not capture the complexity of simultaneous activation."},{"rthcId":"RPEP-06881","title":"Molecular imaging Theranostics of Neuroendocrine Tumors.","authors":"Fortunati, Emilia; Bonazzi, Norma; Zanoni, Lucia; Fanti, Stefano; Ambrosini, Valentina","year":2023,"journal":"Seminars in nuclear medicine, 53(4), 539-554","doi":"10.1053/j.semnuclmed.2022.12.007","pmid":"36623974","tags":["peptide-imaging","somatostatin-analogs"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Peptide receptor radionuclide therapy (PRRT) using somatostatin analogs labeled with lutetium-177 or yttrium-90 is now an established, FDA- and EMA-approved treatment for neuroendocrine tumors (NETs). The same peptides labeled with gallium-68 ([68Ga]-DOTA-peptides) serve as diagnostic imaging agents — making this a true theranostic approach where one peptide family both finds and treats cancer.\n\nThe review highlights emerging advances: personalized treatment schemes, SSTR antagonists (which may outperform current agonists), alpha-emitting radioisotopes for therapy, 18F-labeled somatostatin analogs for improved imaging, and combination strategies pairing PRRT with other treatments.","whyItMatters":"Peptide-based theranostics represent one of the most successful translations of peptide science into clinical medicine. Using the same somatostatin analog peptide to both image tumors with PET scans and then deliver targeted radiation therapy is a paradigm that other cancer types are trying to replicate. This review captures the current state of a field where peptides are genuinely saving lives.","specificNumbers":"PRRT in use since mid-1990s · 177Lu-DOTATATE FDA/EMA approved · 3 main 68Ga-DOTA-peptides for imaging · tumors originate mostly from GI tract and lungs · SSTR expression determines eligibility","methodology":"Narrative review covering the current knowledge base and emerging perspectives for molecular imaging and therapy of neuroendocrine tumors. Covers established somatostatin receptor-targeting peptides, PRRT clinical evidence, and next-generation radiopharmaceuticals under development.","limitations":"As a narrative review, this does not perform a systematic analysis of all available evidence. The emerging strategies discussed (SSTR antagonists, alpha-labeling, 18F-labeled peptides) are still largely in early clinical or preclinical stages. The review focuses primarily on well-differentiated NETs that express somatostatin receptors, which excludes poorly differentiated neuroendocrine carcinomas."},{"rthcId":"RPEP-06882","title":"4D Biochemical Photocustomization of Hydrogel Scaffolds for Biomimetic Tissue Engineering.","authors":"Francis, Ryan M; DeForest, Cole A","year":2023,"journal":"Accounts of materials research, 4(8), 704-715","doi":"10.1021/accountsmr.3c00062","pmid":"39071987","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06883","title":"Immune System and Epidemics: The Role of African Indigenous Bioactive Substances.","authors":"Frazzoli, Chiara; Grasso, Gerardo; Husaini, Danladi Chiroma; Ajibo, Doris Nnenna; Orish, Fortune Chiemelie; Orisakwe, Orish E","year":2023,"journal":"Nutrients, 15(2)","doi":"10.3390/nu15020273","pmid":"36678143","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06884","title":"Efficacy and safety of oral orforglipron in patients with type 2 diabetes: a multicentre, randomised, dose-response, phase 2 study.","authors":"Frias, Juan P; Hsia, Stanley; Eyde, Sarah; Liu, Rong; Ma, Xiaosu; Konig, Manige; Kazda, Christof; Mather, Kieren J; Haupt, Axel; Pratt, Edward; Robins, Deborah","year":2023,"journal":"Lancet (London, England), 402(10400), 472-483","doi":"10.1016/S0140-6736(23)01302-8","pmid":"37369232","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"At week 26, orforglipron at doses of 12 mg or greater produced statistically superior HbA1c reductions compared to placebo. The maximum HbA1c reduction was -2.10% (placebo-adjusted: -1.67%), compared to -0.43% with placebo and -1.10% with injectable dulaglutide 1.5 mg weekly.\n\nWeight loss with orforglipron reached up to -10.1 kg (placebo-adjusted: -7.9 kg), compared to -2.2 kg with placebo and -3.9 kg with dulaglutide.\n\nGastrointestinal adverse events occurred in 44-70% of orforglipron-treated patients (vs. 18% placebo, 34% dulaglutide) but were mostly mild to moderate. Clinically significant hypoglycemia was rare (3 orforglipron patients, 1 dulaglutide). No severe hypoglycemia occurred. The study completion rate was 92%, with 79% completing the full 26 weeks of treatment.","whyItMatters":"This study represents a potential paradigm shift in GLP-1 therapy. Current oral GLP-1 options (like oral semaglutide) are still peptide-based and require strict fasting before dosing. Orforglipron is a non-peptide molecule that can be taken without food or water restrictions, while delivering blood sugar and weight loss results that exceeded an injectable GLP-1 drug. If confirmed in phase 3 trials, this could make GLP-1 therapy far more accessible and convenient for millions of diabetes patients.","specificNumbers":"","methodology":"This was a 26-week, phase 2, double-blind, randomized, multicentre study across 45 centres in the USA, Hungary, Poland, and Slovakia. 383 adults with type 2 diabetes (HbA1c 7.0-10.5%, BMI ≥23) on diet/exercise with or without metformin were randomized to placebo, dulaglutide 1.5 mg weekly, or one of six orforglipron dose groups (3, 12, 24, 36, or 45 mg daily, with two different escalation regimens for the 36 and 45 mg doses). Participants were masked to treatment. The primary endpoint was mean HbA1c change from baseline at week 26.","limitations":"This is a phase 2 dose-finding study with a relatively small sample size (383 participants) and short duration (26 weeks). Long-term safety and efficacy data are needed. The gastrointestinal adverse event rate was high (up to 70%), which could affect real-world adherence. Only 79% completed the full treatment course. The study population was primarily from the US and Eastern Europe, limiting global generalizability. The study was sponsored by Eli Lilly, the drug's manufacturer."},{"rthcId":"RPEP-06885","title":"Efficacy and safety of co-administered once-weekly cagrilintide 2·4 mg with once-weekly semaglutide 2·4 mg in type 2 diabetes: a multicentre, randomised, double-blind, active-controlled, phase 2 trial.","authors":"Frias, Juan P; Deenadayalan, Srikanth; Erichsen, Lars; Knop, Filip K; Lingvay, Ildiko; Macura, Stanislava; Mathieu, Chantal; Pedersen, Sue D; Davies, Melanie","year":2023,"journal":"Lancet (London, England), 402(10403), 720-730","doi":"10.1016/S0140-6736(23)01163-7","pmid":"37364590","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06886","title":"An update on tirzepatide for the management of type 2 diabetes: a focus on the phase 3 clinical development program.","authors":"Frías, Juan Pablo","year":2023,"journal":"Expert review of endocrinology & metabolism, 18(2), 111-130","doi":"10.1080/17446651.2023.2184796","pmid":"36908082","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06887","title":"Mechanisms and regulation of defensins in host defense.","authors":"Fu, Jie; Zong, Xin; Jin, Mingliang; Min, Junxia; Wang, Fudi; Wang, Yizhen","year":2023,"journal":"Signal transduction and targeted therapy, 8(1), 300","doi":"10.1038/s41392-023-01553-x","pmid":"37574471","tags":[],"studyType":"review","evidenceStrength":"consensus","keyFinding":"This comprehensive review synthesizes the current understanding of defensins — a family of cationic antimicrobial peptides produced primarily by Paneth cells, neutrophils, and epithelial cells. The review covers their structural features, evolutionary history, and antimicrobial mechanisms, as well as their broader biological roles in immune homeostasis, chemotaxis, mucosal barrier maintenance, gut microbiota regulation, intestinal development, and regulation of cell death.\n\nThe authors detail the clinical relevance of defensins across multiple disease areas including infectious diseases, inflammatory bowel disease, diabetes and obesity, chronic inflammatory lung disease, periodontitis, and cancer. They also examine how nutrients — fatty acids, amino acids, microelements, plant extracts, and probiotics — regulate defensin expression, offering potential dietary strategies for modulating host defense.","whyItMatters":"Defensins sit at the intersection of innate immunity, gut health, and multiple chronic diseases. This review consolidates decades of research into a single resource, highlighting both the therapeutic promise and the challenges of developing defensin-based therapies. Understanding how diet and nutrients regulate defensin production could lead to practical interventions for improving immune defense.","specificNumbers":"","methodology":"Comprehensive narrative review of published literature on defensins, covering their structure, mechanisms of action, biological functions, clinical relevance across multiple diseases, and nutrient-dependent regulation.","limitations":"As a narrative review, this paper synthesizes existing literature rather than presenting new experimental data. The therapeutic potential discussed is largely theoretical, as defensin-based therapies face significant development challenges including stability, delivery, and potential toxicity that are acknowledged but not resolved."},{"rthcId":"RPEP-06888","title":"A Metalloproteinase Cocktail from the Venom of Protobothrops flavoviridis Cleaves Amyloid Beta Peptides at the α-Cleavage Site.","authors":"Futai, Eugene; Kawasaki, Hajime; Sato, Shinichi; Daoudi, Khadija; Hidaka, Masafumi; Tomita, Taisuke; Ogawa, Tomohisa","year":2023,"journal":"Toxins, 15(8)","doi":"10.3390/toxins15080500","pmid":"37624257","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06889","title":"Cell penetrating peptides-functionalized Licochalcone-A-loaded PLGA nanoparticles for ocular inflammatory diseases: Evaluation of in vitro anti-proliferative effects, stabilization by freeze-drying and characterization of an in-situ forming gel.","authors":"Galindo-Camacho, Ruth M; Haro, Isabel; Gómara, María J; Espina, Marta; Fonseca, Joel; Martins-Gomes, Carlos; Camins, Antoni; Silva, Amélia M; García, María L; Souto, Eliana B","year":2023,"journal":"International journal of pharmaceutics, 639, 122982","doi":"10.1016/j.ijpharm.2023.122982","pmid":"37116598","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06890","title":"Action Mechanisms of Metformin Combined with Exenatide and Metformin Only in the Treatment of PCOS in Obese Patients.","authors":"Gan, Jingwen; Chen, Jie; Ma, Rui-Lin; Deng, Yan; Ding, Xue-Song; Zhu, Shi-Yang; Sun, Ai-Jun","year":2023,"journal":"International journal of endocrinology, 2023, 4288004","doi":"10.1155/2023/4288004","pmid":"38131036","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06891","title":"Tirzepatide versus insulin glargine as second-line or third-line therapy in type 2 diabetes in the Asia-Pacific region: the SURPASS-AP-Combo trial.","authors":"Gao, Leili; Lee, Byung Wan; Chawla, Manoj; Kim, Joshua; Huo, Li; Du, Liying; Huang, Yan; Ji, Linong","year":2023,"journal":"Nature medicine, 29(6), 1500-1510","doi":"10.1038/s41591-023-02344-1","pmid":"37231074","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"All three tirzepatide doses were both non-inferior and superior to insulin glargine for HbA1c reduction at week 40:\n- Tirzepatide 5mg: -2.24% (treatment difference vs. insulin: -1.29%)\n- Tirzepatide 10mg: -2.44% (treatment difference: -1.49%)\n- Tirzepatide 15mg: -2.49% (treatment difference: -1.54%)\n- Insulin glargine: -0.95%\n(All P<0.001)\n\nHbA1c <7.0% targets achieved: tirzepatide 75.4-86.0% vs. insulin 23.7% (P<0.001). Body weight changes: tirzepatide -5.0 to -7.2 kg vs. insulin +1.5 kg (P<0.001). No severe hypoglycemia reported with tirzepatide.","whyItMatters":"Type 2 diabetes is particularly prevalent in Asia-Pacific populations, where it often develops at lower BMI than in Western populations. This trial is the first to demonstrate tirzepatide's superiority over insulin specifically in a predominantly Chinese/Asian population. The enormous efficacy gap — tirzepatide reduced HbA1c by up to 2.6 times more than insulin — combined with weight loss instead of weight gain could fundamentally change how diabetes is managed in this region, potentially making insulin a second-choice rather than first-line injectable therapy.","specificNumbers":"","methodology":"SURPASS-AP-Combo was a phase 3, randomized, open-label trial at 66 hospitals in China, South Korea, Australia, and India. Insulin-naive adults with type 2 diabetes uncontrolled on metformin (with or without a sulphonylurea) were randomized 1:1:1:1 to weekly tirzepatide 5mg, 10mg, or 15mg or daily insulin glargine. The primary endpoint was non-inferiority of HbA1c change from baseline to week 40. Key secondary endpoints included superiority testing, HbA1c target achievement rates, and weight change. Of 917 randomized patients, 83.2% were in China.","limitations":"The open-label design means both patients and investigators knew which treatment was given, which could influence subjective outcomes. Insulin glargine was titrated to target but the specific titration results and final doses are not detailed — undertitration could have disadvantaged the insulin group. The 40-week duration may not capture long-term outcomes. The predominantly Chinese population (83.2%) limits direct generalizability to other Asia-Pacific ethnic groups. Cost-effectiveness was not assessed — tirzepatide is significantly more expensive than insulin glargine."},{"rthcId":"RPEP-06892","title":"Inhibition of talin-induced integrin activation by a double-hit stapled peptide.","authors":"Gao, Tong; Cho, Eun-Ah; Zhang, Pingfeng; Wu, Jinhua","year":2023,"journal":"Structure (London, England : 1993), 31(8), 948-957.e3","doi":"10.1016/j.str.2023.05.016","pmid":"37369205","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The stapled peptide S-TBS, derived from the talin-binding segment of RIAM, exhibited stronger binding to talin than the unmodified peptide and inhibited the talin-integrin interaction. X-ray crystallography confirmed S-TBS binds to the talin rod through the same interface as the natural TBS sequence.\n\nCritically, the helical stapled peptide demonstrated excellent cell permeability (a common challenge for peptide drugs) and effectively suppressed integrin activation in living cells in a talin-dependent manner. The 'double-hit' approach — targeting two distinct sites with a single peptide — represents a novel design strategy for multi-specific peptidomimetic inhibitors.","whyItMatters":"Integrins are drug targets in cancer, thrombosis, autoimmune diseases, and fibrosis, but most existing integrin drugs target the extracellular binding face. This study opens a new therapeutic angle — blocking integrin activation from inside the cell by disrupting the talin-integrin signaling pathway. The stapled peptide technology also demonstrates that cell-permeable peptides can effectively modulate intracellular protein-protein interactions, expanding the druggable proteome.","specificNumbers":"","methodology":"Researchers designed the stapled peptide S-TBS by incorporating a molecular staple into the RIAM talin-binding segment to stabilize its helical structure. Binding affinity was measured through biophysical assays. The binding mode was confirmed by X-ray crystallography of the S-TBS:talin complex. Cell permeability was assessed using fluorescence-based assays. Functional inhibition of integrin activation was tested in cell-based assays measuring integrin activation states.","limitations":"This is a proof-of-concept study with no animal testing. Cell-based assays demonstrate functional inhibition, but in vivo pharmacokinetics, biodistribution, and therapeutic efficacy remain unknown. The selectivity of S-TBS for talin versus other proteins was not comprehensively characterized. Long-term stability and potential toxicity of the stapled peptide were not assessed. Translation from cell-based to animal studies may reveal additional challenges."},{"rthcId":"RPEP-06893","title":"Substance P reversibly compromises the integrity and function of blood-brain barrier.","authors":"Gao, Xin; Bayraktutan, Ulvi","year":2023,"journal":"Peptides, 167, 171048","doi":"10.1016/j.peptides.2023.171048","pmid":"37390897","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06894","title":"Screening of Oral Potential Angiotensin-Converting Enzyme Inhibitory Peptides from Zizyphus jujuba Proteins Based on Gastrointestinal Digestion In Vivo.","authors":"Gao, Xinchang; Zhang, Chaoying; Wang, Ning; Lin, Jin-Ming; Dang, Yali; Zhao, Yufen","year":2023,"journal":"International journal of molecular sciences, 24(21)","doi":"10.3390/ijms242115848","pmid":"37958831","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06895","title":"Influence of chronic kidney disease and its severity on the efficacy of semaglutide in type 2 diabetes patients: a multicenter real-world study.","authors":"García de Lucas, María Dolores; Caballero, Irene; Fernández-García, José Carlos; Domínguez-Rodríguez, Manuel; Moreno-Moreno, Paloma; Jiménez-Millán, Anabel; Botana-López, Manuel; Avilés, Beatriz; Merino-Torres, Juan Francisco; Soto, Alfonso; Tejera, Cristina; Morales, Cristóbal","year":2023,"journal":"Frontiers in endocrinology, 14, 1240279","doi":"10.3389/fendo.2023.1240279","pmid":"37955013","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06896","title":"Effects of GLP-1 receptor agonists on neurological complications of diabetes.","authors":"García-Casares, Natalia; González-González, Guillermo; de la Cruz-Cosme, Carlos; Garzón-Maldonado, Francisco J; de Rojas-Leal, Carmen; Ariza, María J; Narváez, Manuel; Barbancho, Miguel Ángel; García-Arnés, Juan Antonio; Tinahones, Francisco J","year":2023,"journal":"Reviews in endocrine & metabolic disorders, 24(4), 655-672","doi":"10.1007/s11154-023-09807-3","pmid":"37231200","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06897","title":"Milk Allergen Micro-Array (MAMA) for Refined Detection of Cow's-Milk-Specific IgE Sensitization.","authors":"Garib, Victoria; Trifonova, Daria; Freidl, Raphaela; Linhart, Birgit; Schlederer, Thomas; Douladiris, Nikolaos; Pampura, Alexander; Dolotova, Daria; Lepeshkova, Tatiana; Gotua, Maia; Varlamov, Evgeniy; Beltyukov, Evgeny; Naumova, Veronika; Taka, Styliani; Kiyamova, Alina; Katsamaki, Stefani; Karaulov, Alexander; Valenta, Rudolf","year":2023,"journal":"Nutrients, 15(10)","doi":"10.3390/nu15102401","pmid":"37242284","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06898","title":"Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial.","authors":"Garvey, W Timothy; Frias, Juan P; Jastreboff, Ania M; le Roux, Carel W; Sattar, Naveed; Aizenberg, Diego; Mao, Huzhang; Zhang, Shuyu; Ahmad, Nadia N; Bunck, Mathijs C; Benabbad, Imane; Zhang, Xiaotian M","year":2023,"journal":"Lancet (London, England), 402(10402), 613-626","doi":"10.1016/S0140-6736(23)01200-X","pmid":"37385275","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06899","title":"Changes in body mass, appetite-related hormones, and appetite sensation in women during 4 days of hypobaric hypoxic exposure equivalent to 3,500-m altitude.","authors":"Gatterer, Hannes; Roche, Johanna; Turner, Rachel; Vinetti, Giovanni; Roveri, Giulia; Schlittler, Maja; Kob, Michael; Walzl, Anna; Dal Cappello, Tomas; Debevec, Tadej; Siebenmann, Christoph","year":2023,"journal":"Journal of applied physiology (Bethesda, Md. : 1985), 134(1), 133-141","doi":"10.1152/japplphysiol.00369.2022","pmid":"36476162","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06900","title":"The Impact of Substantial Improvements in HbA1c and Weight Loss on the Medication Preferences of People with Type 2 Diabetes.","authors":"Gelhorn, Heather L; Osumili, Beatrice; Brown, Katelyn; Ross, Melissa M; Schulz, Andrea; Fernandez, Gabriela; Boye, Kristina S","year":2023,"journal":"Patient preference and adherence, 17, 793-805","doi":"10.2147/PPA.S401465","pmid":"36987498","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"When presented with the clinical profiles of tirzepatide (5, 10, and 15mg) versus semaglutide 1mg based on head-to-head trial data, predicted preference for tirzepatide was 95.6% in the US and 86.3% in the UK.\n\nThe key drivers of preference differed between countries: US patients weighted HbA1c reduction most heavily (26.3% relative attribute importance), while UK patients prioritized avoiding hypoglycemia (32.8%). Both groups preferred greater HbA1c improvement, greater weight loss, lower nausea frequency, lower hypoglycemia risk, and the single-use pre-filled pen delivery system. Weight reduction and nausea frequency also significantly influenced preferences.","whyItMatters":"As tirzepatide and semaglutide compete in the diabetes and obesity markets, understanding what patients actually value helps guide treatment decisions and healthcare resource allocation. This study shows that when patients are informed about the clinical differences, they strongly prefer the dual-action tirzepatide profile — but the reasons vary by healthcare culture. The cross-cultural difference (US prioritizes efficacy, UK prioritizes safety) has implications for how these drugs are positioned and prescribed in different markets.","specificNumbers":"","methodology":"620 injection-naive adults with type 2 diabetes (301 US, 319 UK) completed a web-based discrete choice experiment — a validated survey method where participants choose between hypothetical treatment profiles that vary across defined attributes. Five treatment attributes were tested: delivery system, nausea frequency, hypoglycemia frequency, HbA1c reduction, and weight reduction. Attribute levels were derived from the SURPASS-2 head-to-head clinical trial comparing tirzepatide doses to semaglutide 1mg. Data were analyzed using multinomial mixed logit models separately by country.","limitations":"The study was funded by Eli Lilly (tirzepatide's manufacturer), which introduces potential sponsorship bias in study design and attribute selection. Participants evaluated hypothetical profiles rather than experiencing the medications firsthand. Only injection-naive patients were included, limiting generalizability to those already on injectable therapy. Semaglutide was represented at only the 1mg dose — higher doses (2.4mg for obesity) could change the preference balance. The discrete choice format simplifies real-world decision-making."},{"rthcId":"RPEP-06901","title":"Biomarker Changes Associated With Both Dulaglutide and Cardiovascular Events in the REWIND Randomized Controlled Trial: A Nested Case-Control Post Hoc Analysis.","authors":"Gerstein, Hertzel C; Lee, Shun-Fu; Paré, Guillaume; Bethel, M Angelyn; Colhoun, Helen M; Hoover, Anastasia; Lakshmanan, Mark; Lin, Yanzhu; Pirro, Valentina; Qian, Hui-Rong; Ruotolo, Giacomo; Ryden, Lars; Wilson, Jonathan M; Duffin, Kevin L","year":2023,"journal":"Diabetes care, 46(5), 1046-1051","doi":"10.2337/dc22-2397","pmid":"36897834","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Compared to placebo over 2 years, dulaglutide was associated with greater reductions or lesser rises in NT-proBNP, GDF-15, high-sensitivity CRP, and a greater rise in C-peptide. It also reduced 2-hydroxybutyric acid and increased threonine levels.\n\nCritically, of these biomarkers, only NT-proBNP and GDF-15 were also independently associated with cardiovascular events (MACE). NT-proBNP: OR 1.267 (95% CI 1.119–1.435, p<0.001); GDF-15: OR 1.937 (95% CI 1.424–2.634, p<0.001). This dual association — reduced by dulaglutide AND predictive of heart events — suggests these markers may mediate the drug's cardiovascular protection.","whyItMatters":"GLP-1 drugs clearly reduce heart disease risk in diabetes, but the mechanism remains debated. This study identifies NT-proBNP and GDF-15 as potential mediators — they're reduced by dulaglutide and independently predict cardiovascular events. This could guide development of better cardiovascular risk markers and help explain which patients benefit most from GLP-1 therapy.","specificNumbers":"","methodology":"Nested case-control post-hoc analysis of the REWIND randomized controlled trial. Fasting plasma samples from baseline and 2 years were analyzed in 824 participants who experienced MACE and 845 matched controls. 19 protein biomarkers were measured in the full cohort; 135 metabolites were measured in a subset of 1,201 participants. Linear and logistic regression models identified biomarkers associated with both dulaglutide treatment and cardiovascular events.","limitations":"This is a post-hoc analysis, not a pre-specified endpoint, so the findings are hypothesis-generating rather than definitive. Biomarker associations don't prove causation — dulaglutide could reduce these markers without that being the mechanism of cardiovascular protection. Only baseline and 2-year samples were analyzed, so biomarker trajectories between those time points are unknown."},{"rthcId":"RPEP-06902","title":"Molecular simulations of SSTR2 dynamics and interaction with ligands.","authors":"Gervasoni, Silvia; Guccione, Camilla; Fanti, Viviana; Bosin, Andrea; Cappellini, Giancarlo; Golosio, Bruno; Ruggerone, Paolo; Malloci, Giuliano","year":2023,"journal":"Scientific reports, 13(1), 4768","doi":"10.1038/s41598-023-31823-1","pmid":"36959237","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Microsecond-long multi-copy molecular dynamics simulations revealed that the apo (empty) SSTR2 receptor is more flexible than when bound to ligands. Extracellular loop 2 (ECL2) closes upon binding the agonist octreotide but not the antagonist CYN154806, providing a structural explanation for agonist vs. antagonist selectivity.\n\nAll peptide ligands (somatostatin, octreotide, and CYN154806) interact similarly with residues deep in the binding pocket. However, agonists and the antagonist show distinct interaction patterns with residues at the outer portion of the pocket near the extracellular loops, which is the key structural feature distinguishing receptor activation from blockade.","whyItMatters":"Octreotide and related somatostatin analogs are mainstay treatments for neuroendocrine tumors and are used in both therapy and diagnostic imaging (theranostics). Understanding exactly how these peptides interact with SSTR2 at the atomic level helps researchers design improved analogs with better selectivity, potency, or pharmacological properties for cancer treatment.","specificNumbers":"","methodology":"Computational structural biology study. Used recently solved experimental crystal/cryo-EM structures of SSTR2 as starting points. Performed microsecond-long multi-copy molecular dynamics simulations of three receptor states: active (agonist-bound), inactive (antagonist-bound), and apo (empty). Analysis included interaction fingerprinting and free energy calculations to characterize binding of somatostatin, octreotide, and the antagonist CYN154806.","limitations":"This is entirely a computational study — predictions would need experimental validation. Molecular dynamics simulations, even at microsecond timescales, may not capture all biologically relevant conformational changes. The study focused on SSTR2 only; other somatostatin receptor subtypes may behave differently. Membrane environment and intracellular G-protein coupling were simplified."},{"rthcId":"RPEP-06903","title":"Cell-Penetrating and Targeted Peptides Delivery Systems as Potential Pharmaceutical Carriers for Enhanced Delivery across the Blood-Brain Barrier (BBB).","authors":"Ghorai, Soma Mondal; Deep, Auroni; Magoo, Devanshi; Gupta, Chetna; Gupta, Nikesh","year":2023,"journal":"Pharmaceutics, 15(7)","doi":"10.3390/pharmaceutics15071999","pmid":"37514185","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06904","title":"Targeting redox imbalance in neurodegeneration: characterizing the role of GLP-1 receptor agonists.","authors":"Ghosh, Puja; Fontanella, Rosaria Anna; Scisciola, Lucia; Pesapane, Ada; Taktaz, Fatemeh; Franzese, Martina; Puocci, Armando; Ceriello, Antonio; Prattichizzo, Francesco; Rizzo, Maria Rosaria; Paolisso, Giuseppe; Barbieri, Michelangela","year":2023,"journal":"Theranostics, 13(14), 4872-4884","doi":"10.7150/thno.86831","pmid":"37771773","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06905","title":"Biocompatible Short-Peptides Fibrin Co-assembled Hydrogels.","authors":"Gila-Vilchez, Cristina; Mañas-Torres, Mari Carmen; García-García, Óscar Darío; Escribano-Huesca, Alfredo; Rodríguez-Arco, Laura; Carriel, Víctor; Rodriguez, Ismael; Alaminos, Miguel; Lopez-Lopez, Modesto Torcuato; Álvarez de Cienfuegos, Luis","year":2023,"journal":"ACS applied polymer materials, 5(3), 2154-2165","doi":"10.1021/acsapm.2c02164","pmid":"36935654","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The co-assembly of fibrinogen with Fmoc-FF and Fmoc-RGD peptides produced a novel supramolecular fiber type with tunable morphology and mechanical properties. Key findings include:\n\n- The composite hydrogels had significantly improved mechanical properties compared to pure fibrin gels\n- Ex vivo testing confirmed excellent biocompatibility\n- In vivo experiments showed no inflammatory response or tissue damage\n- The gels were completely resorbed in a short time\n- The three-component system co-assembles under physiological conditions triggered by thrombin, enabling injectable formulations","whyItMatters":"Fibrin-based hydrogels are already clinically established but limited by poor mechanical strength and the high cost of human plasma-derived fibrinogen. By adding inexpensive, easily synthesized short peptides, the researchers created a stronger, more versatile material that retains fibrin's biocompatibility. The injectable, self-assembling nature and complete resorption make these composites attractive for next-generation drug delivery, cell therapy, and tissue engineering applications.","specificNumbers":"","methodology":"The researchers prepared composite hydrogels by combining fibrinogen (from human plasma) with two Fmoc-protected short peptides — Fmoc-diphenylalanine (Fmoc-FF) and Fmoc-RGD — under thrombin-triggered self-assembly conditions. They performed comprehensive characterization including chemical analysis, physical/mechanical testing, ex vivo biocompatibility assessment, and in vivo implantation studies to evaluate inflammatory response and resorption.","limitations":"The abstract does not provide specific mechanical property values or quantitative comparisons with pure fibrin gels. The duration of 'short time' for complete resorption is not specified. The in vivo experiments appear to assess biocompatibility rather than therapeutic efficacy for a specific application. Long-term stability and degradation kinetics are not discussed. The scale-up feasibility for clinical manufacturing is not addressed."},{"rthcId":"RPEP-06906","title":"Multicomponent Peptide-Based Hydrogels Containing Chemical Functional Groups as Innovative Platforms for Biotechnological Applications.","authors":"Giordano, Sabrina; Gallo, Enrico; Diaferia, Carlo; Rosa, Elisabetta; Carrese, Barbara; Borbone, Nicola; Scognamiglio, Pasqualina Liana; Franzese, Monica; Oliviero, Giorgia; Accardo, Antonella","year":2023,"journal":"Gels (Basel, Switzerland), 9(11)","doi":"10.3390/gels9110903","pmid":"37998993","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06907","title":"The real-world observational prospective study of health outcomes with dulaglutide and liraglutide in patients with type 2 diabetes (TROPHIES): Final, 24-month analysis of time to first significant treatment change, treatment persistence and clinical outcomes.","authors":"Giorgino, Francesco; Guerci, Bruno; Füchtenbusch, Martin; Lebrec, Jérémie; Boye, Kristina; Orsini Federici, Marco; Heitmann, Elke; Dib, Anne; Yu, Maria; Sapin, Hélène; García-Pérez, Luis-Emilio","year":2023,"journal":"Diabetes, obesity & metabolism, 25(12), 3465-3477","doi":"10.1111/dom.15244","pmid":"37700627","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06908","title":"Pmu1a, a novel spider toxin with dual inhibitory activity at pain targets hNaV 1.7 and hCaV 3 voltage-gated channels.","authors":"Giribaldi, Julien; Chemin, Jean; Tuifua, Marie; Deuis, Jennifer R; Mary, Rosanna; Vetter, Irina; Wilson, David T; Daly, Norelle L; Schroeder, Christina I; Bourinet, Emmanuel; Dutertre, Sébastien","year":2023,"journal":"The FEBS journal, 290(14), 3688-3702","doi":"10.1111/febs.16773","pmid":"36912793","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06909","title":"Thymosin β4 and prothymosin α promote cardiac regeneration post-ischaemic injury in mice.","authors":"Gladka, Monika M; Johansen, Anne Katrine Z; van Kampen, Sebastiaan J; Peters, Marijn M C; Molenaar, Bas; Versteeg, Danielle; Kooijman, Lieneke; Zentilin, Lorena; Giacca, Mauro; van Rooij, Eva","year":2023,"journal":"Cardiovascular research, 119(3), 802-812","doi":"10.1093/cvr/cvac155","pmid":"36125329","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Using single-cell RNA sequencing, researchers identified a distinct gene expression profile in the rare cardiomyocytes that enter the cell cycle after myocardial infarction in mice. They found increased DNA synthesis (EdU incorporation) in cardiomyocytes 3 days post-infarction, confirmed by clonal expansion in the border zone of infarcted tissue using multi-color lineage tracing.\n\nAmong the enriched genes in proliferating cardiomyocytes, a combination of thymosin β4 (TMSB4) and prothymosin α (PTMA) proved most effective. When delivered therapeutically to the heart wall after ischemic injury, this two-peptide cocktail promoted cardiomyocyte proliferation and attenuated cardiac dysfunction. The study demonstrates that both activating cell division and creating a permissive microenvironment are necessary for cardiac regeneration.","whyItMatters":"Heart disease is the leading cause of death worldwide, and a heart attack permanently destroys heart muscle because adult cardiomyocytes barely divide. Finding ways to restart heart cell division has been a holy grail of cardiac research. This study is significant because it identifies a specific peptide combination — thymosin β4 and prothymosin α — that promotes heart regeneration in a mammalian model, moving beyond single-factor approaches and showing that creating a supportive environment is as important as triggering cell division itself.","specificNumbers":"","methodology":"Researchers induced myocardial infarction (heart attacks) in mice and used EdU incorporation and multi-color lineage tracing to identify and track proliferating cardiomyocytes. Single-cell RNA sequencing of cardiomyocytes at 3 days post-injury revealed the transcriptional profile of cycling cells. Candidate genes were tested by combinatorial overexpression in neonatal rat cardiomyocytes and postnatal day 12 mice. The most promising gene combinations were then therapeutically delivered into the myocardial wall of adult mice after ischemic injury to assess regenerative effects.","limitations":"This is a preclinical study in mice, and mouse hearts have somewhat greater regenerative capacity than human hearts. The gene delivery approach used (direct myocardial wall injection) would need significant adaptation for clinical use. Long-term outcomes and safety were not assessed. The exact mechanisms by which TMSB4 and PTMA create a permissive environment for proliferation require further investigation. Results in neonatal rat cardiomyocytes and P12 mice may not fully predict adult human responses."},{"rthcId":"RPEP-06910","title":"Research Note: Analysis of immune responses in broilers after vaccination against Campylobacter jejuni.","authors":"Gloanec, Noémie; Dory, Daniel; Quesne, Ségolène; Béven, Véronique; Poezevara, Typhaine; Amelot, Michel; Chemaly, Marianne; Guyard-Nicodème, Muriel","year":2023,"journal":"Poultry science, 102(4), 102510","doi":"10.1016/j.psj.2023.102510","pmid":"36764139","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06911","title":"Antibody-Drug Conjugates: A Review of Approved Drugs and Their Clinical Level of Evidence.","authors":"Gogia, Pooja; Ashraf, Hamza; Bhasin, Sidharth; Xu, Yiqing","year":2023,"journal":"Cancers, 15(15)","doi":"10.3390/cancers15153886","pmid":"37568702","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06912","title":"Peptide-conjugated antimiRs improve myotonic dystrophy type 1 phenotypes by promoting endogenous MBNL1 expression.","authors":"González-Martínez, Irene; Cerro-Herreros, Estefanía; Moreno, Nerea; García-Rey, Andrea; Espinosa-Espinosa, Jorge; Carrascosa-Sàez, Marc; Piqueras-Losilla, Diego; Arzumanov, Andrey; Seoane-Miraz, David; Jad, Yahya; Raz, Richard; Wood, Matthew J; Varela, Miguel A; Llamusí, Beatriz; Artero, Rubén","year":2023,"journal":"Molecular therapy. Nucleic acids, 34, 102024","doi":"10.1016/j.omtn.2023.09.001","pmid":"37744174","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Peptide-conjugated antisense oligonucleotides (CPP-PMOs) targeting miR-23b and miR-218 significantly increased MBNL1 protein levels in myotonic dystrophy type 1 (DM1) cells. Some candidates achieved this at concentrations nearly two orders of magnitude below the median toxic concentration, with up to a 5.38-fold better therapeutic window compared to previous antagomiR approaches.\n\nIn HSALR mouse models, intravenous injections of CPP-PMOs improved molecular, histopathological, and functional disease phenotypes without signs of toxicity, demonstrating successful in vivo delivery to affected tissues.","whyItMatters":"Myotonic dystrophy type 1 currently has no approved treatment that addresses its root molecular cause. A major barrier has been delivering therapeutic molecules to affected muscle and nerve tissues. By conjugating antisense oligonucleotides to cell-penetrating peptides, this study demonstrates a delivery strategy that works both in cells and in living animals — a critical step toward viable DM1 therapy.","specificNumbers":"","methodology":"The researchers designed antisense oligonucleotides (antimiRs) using phosphorodiamidate morpholino oligonucleotide (PMO) chemistry, conjugated to cell-penetrating peptides. These CPP-PMOs were tested in DM1 patient-derived cells to measure MBNL1 protein levels and toxicity, then administered via intravenous injection in HSALR transgenic mice — an established DM1 animal model — to assess molecular, tissue-level, and functional outcomes.","limitations":"The study used a mouse model (HSALR) that mimics DM1 but does not perfectly replicate the human disease. Long-term safety and efficacy beyond the study period were not assessed. Translation from mouse to human dosing and tissue distribution remains uncertain. The sample sizes for animal experiments were not specified in the abstract."},{"rthcId":"RPEP-06913","title":"GLP-1R agonists demonstrate potential to treat Wolfram syndrome in human preclinical models.","authors":"Gorgogietas, Vyron; Rajaei, Bahareh; Heeyoung, Chae; Santacreu, Bruno J; Marín-Cañas, Sandra; Salpea, Paraskevi; Sawatani, Toshiaki; Musuaya, Anyishai; Arroyo, María N; Moreno-Castro, Cristina; Benabdallah, Khadija; Demarez, Celine; Toivonen, Sanna; Cosentino, Cristina; Pachera, Nathalie; Lytrivi, Maria; Cai, Ying; Carnel, Lode; Brown, Cris; Urano, Fumihiko; Marchetti, Piero; Gilon, Patrick; Eizirik, Decio L; Cnop, Miriam; Igoillo-Esteve, Mariana","year":2023,"journal":"Diabetologia, 66(7), 1306-1321","doi":"10.1007/s00125-023-05905-8","pmid":"36995380","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06914","title":"Cell Penetrating Peptides: Classification, Mechanisms, Methods of Study, and Applications.","authors":"Gori, Alessandro; Lodigiani, Giulia; Colombarolli, Stella G; Bergamaschi, Greta; Vitali, Alberto","year":2023,"journal":"ChemMedChem, 18(17), e202300236","doi":"10.1002/cmdc.202300236","pmid":"37389978","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06915","title":"Membrane-Active Peptides and Their Potential Biomedical Application.","authors":"Gostaviceanu, Andreea; Gavrilaş, Simona; Copolovici, Lucian; Copolovici, Dana Maria","year":2023,"journal":"Pharmaceutics, 15(8)","doi":"10.3390/pharmaceutics15082091","pmid":"37631305","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06916","title":"Unexpected gender differences in progressive supranuclear palsy reveal efficacy for davunetide in women.","authors":"Gozes, Illana; Shapira, Guy; Lobyntseva, Alexandra; Shomron, Noam","year":2023,"journal":"Translational psychiatry, 13(1), 319","doi":"10.1038/s41398-023-02618-9","pmid":"37845254","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06917","title":"Growth hormone-releasing hormone antagonist MIA-602 inhibits inflammation induced by SARS-CoV-2 spike protein and bacterial lipopolysaccharide synergism in macrophages and human peripheral blood mononuclear cells.","authors":"Granato, Giuseppina; Gesmundo, Iacopo; Pedrolli, Francesca; Kasarla, Ramesh; Begani, Laura; Banfi, Dana; Bruno, Stefania; Lopatina, Tatiana; Brizzi, Maria Felice; Cai, Renzhi; Sha, Wei; Ghigo, Ezio; Schally, Andrew V; Granata, Riccarda","year":2023,"journal":"Frontiers in immunology, 14, 1231363","doi":"10.3389/fimmu.2023.1231363","pmid":"37649486","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06918","title":"INTERCEPT H3: a multicenter phase I peptide vaccine trial for the treatment of H3-mutated diffuse midline gliomas.","authors":"Grassl, Niklas; Sahm, Katharina; Süße, Heike; Poschke, Isabel; Bunse, Lukas; Bunse, Theresa; Boschert, Tamara; Mildenberger, Iris; Rupp, Anne-Kathleen; Ewinger, Max Philipp; Lanz, Lisa-Marie; Denk, Monika; Tabatabai, Ghazaleh; Ronellenfitsch, Michael W; Herrlinger, Ulrich; Glas, Martin; Krex, Dietmar; Vajkoczy, Peter; Wick, Antje; Harting, Inga; Sahm, Felix; von Deimling, Andreas; Bendszus, Martin; Wick, Wolfgang; Platten, Michael","year":2023,"journal":"Neurological research and practice, 5(1), 55","doi":"10.1186/s42466-023-00282-4","pmid":"37853454","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"This is a trial protocol paper, not a results paper. The key preclinical finding supporting the trial is that the H3K27M-vac peptide vaccine induced mutation-specific immune responses and suppressed growth of H3K27M-positive tumors in MHC-humanized rodent models.\n\nThe trial design calls for 15 adult patients with newly diagnosed H3K27M-mutant diffuse midline gliomas to receive the 27-amino-acid peptide vaccine alongside radiation therapy and the PD-L1-targeting antibody atezolizumab. Vaccines are administered bi-weekly during radiation, then every 6 weeks for a total of 11 doses.","whyItMatters":"Diffuse midline gliomas are among the most devastating cancers with no effective treatments. The H3K27M mutation is an ideal vaccine target because it is clonal (present in virtually all tumor cells), tumor-specific, and drives the disease. If this peptide vaccine can safely generate immune responses in patients, it could open a new treatment avenue for a cancer that is currently untreatable.","specificNumbers":"","methodology":"Non-controlled, open-label, single-arm, multicenter Phase I clinical trial across multiple German centers. Fifteen adult patients with newly diagnosed H3K27M-mutant diffuse midline gliomas will be enrolled. The 27mer peptide vaccine H3K27M-vac is administered alongside standard radiotherapy, followed by combination treatment with atezolizumab. A safety lead-in enrolls the first 3 patients sequentially. Primary endpoints are safety, tolerability, and immunogenicity.","limitations":"This is a trial protocol, not a results paper — no efficacy or safety data from human patients are available yet. The trial is small (15 patients) and uncontrolled, designed primarily for safety assessment. The patient population is limited to adults, while diffuse midline gliomas also affect children. Success in rodent models does not guarantee clinical efficacy. The open-label, single-arm design does not allow comparison to standard of care."},{"rthcId":"RPEP-06919","title":"PEGylation of a Peptide-Based Amphiphilic Delivery Agent and Influence on Protein Delivery to Cells.","authors":"Greschner, Andrea A; Brahiti, Nadine; Auger, Maud; Hu, Lei; Soleymani Abyaneh, Hoda; Barbeau, Xavier; Parent, Victor; Gaillet, Bruno; Guay, David; Soultan, Al-Halifa; Gauthier, Marc A","year":2023,"journal":"Biomacromolecules, 24(11), 4890-4900","doi":"10.1021/acs.biomac.3c00603","pmid":"37862236","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06920","title":"Effects of Incretin-Based Treatment on the Diastolic (Dys)Function in Patients with Uncontrolled Type 2 Diabetes Mellitus: A Prospective Study with 1-Year Follow-Up.","authors":"Grigorescu, Elena-Daniela; Lăcătușu, Cristina-Mihaela; Floria, Mariana; Cazac, Georgiana-Diana; Onofriescu, Alina; Sauciuc, Livia-Amira; Ceasovschih, Alexandr; Crețu, Ioana; Mihai, Bogdan-Mircea; Șorodoc, Laurențiu","year":2023,"journal":"Diagnostics (Basel, Switzerland), 13(17)","doi":"10.3390/diagnostics13172817","pmid":"37685355","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06921","title":"Comparative transport analysis of cell penetrating peptides and Lysosomal sequences for selective tropism towards RPE cells.","authors":"Grohn, Kris; Parella, Kyle; Lumen, Ellie; Colegrove, Hanna; Bjork, Victor; Franceski, Alana; Wolfe, Aaron; Moody, Kelsey","year":2023,"journal":"Research square","doi":"10.21203/rs.3.rs-3651531/v1","pmid":"38234750","tags":["cell-penetrating-peptides","eye-disease"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Researchers developed a combinatorial library of cell-penetrating peptides (CPPs) combined with lysosomal sorting signals and tested them for cell-type specificity in retinal cells versus corneal cells. Several CPP candidates showed up to 4-fold greater internalization in ARPE19 retinal pigment epithelium cells compared to B3 corneal lens cells, demonstrating that CPPs can be engineered for cell-type selectivity rather than the non-specific uptake typically seen.\n\nFollow-up cargo transport studies confirmed that the selected CPPs could effectively deliver payload into ARPE19 cells and target it specifically to lysosomes — the cellular organelles where storage diseases cause dysfunction and eventual blindness.","whyItMatters":"The eye contains many different cell types in close proximity, and diseases often affect specific ones. Lysosomal storage diseases in the retinal pigment epithelium (RPE) impair the cell's ability to clear waste, leading to RPE death and blindness. Current drug delivery methods struggle to target RPE cells specifically without affecting neighboring cell types. Demonstrating that CPPs can be engineered for 4x selective uptake into RPE cells — and can deliver cargo directly to lysosomes — opens a new approach for treating retinal diseases with precision-targeted peptide delivery.","specificNumbers":"Up to 4x internalization efficiency in RPE cells vs. corneal cells · combinatorial CPP + lysosomal sorting signal library · effective lysosomal targeting confirmed in ARPE19 cells","methodology":"A combinatorial library was created by combining different cell-penetrating peptides with lysosomal sorting signals. The library was screened on two human cell lines: ARPE19 (retinal pigment epithelium) and B3 (corneal lens cells). Internalization efficiency and cell-type selectivity were measured by comparing uptake between the two cell types. Cargo transport studies assessed whether the CPPs could deliver payload to lysosomes within ARPE19 cells.","limitations":"This is a preprint (Research Square) that has not been peer-reviewed. All experiments used cell lines (ARPE19 and B3), not primary retinal cells or in vivo models. The 4x selectivity, while promising, may not translate to the complex multicellular environment of the living eye. No therapeutic cargo was delivered — only proof-of-concept internalization was demonstrated. The RPE cell line ARPE19 may not fully represent primary RPE cell behavior."},{"rthcId":"RPEP-06922","title":"In silico identification of novel ACE and DPP-IV inhibitory peptides derived from buffalo milk proteins and evaluation of their inhibitory mechanisms.","authors":"Gu, Yuxiang; Li, Xing; Qi, Xiaofen; Ma, Ying; Chan, Eric Chun Yong","year":2023,"journal":"Amino acids, 55(2), 161-171","doi":"10.1007/s00726-022-03202-z","pmid":"36701004","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Six novel peptides were identified from in silico proteolysis of buffalo milk proteins: two ACE inhibitors (KPW and RGP) and four DPP-IV inhibitors (RGP, KPW, FPK, and KFTW). Laboratory validation confirmed their activity:\n\nACE inhibition: KPW (IC50 = 136.28 ± 10.77 μM, competitive inhibitor) and RGP (IC50 = 104.72 ± 8.37 μM, competitive inhibitor).\n\nDPP-IV inhibition: KPW (IC50 = 82.52 ± 10.37 μM, mixed-type inhibitor), FPK (IC50 = 126.57 ± 8.45 μM, mixed-type inhibitor), and KFTW (IC50 = 873.92 ± 32.89 μM, competitive inhibitor).\n\nNotably, KPW inhibited both ACE and DPP-IV, making it a dual-activity peptide.","whyItMatters":"Food-derived bioactive peptides are gaining attention as natural alternatives or supplements to pharmaceutical drugs for blood pressure and blood sugar management. Buffalo milk is consumed by over 2 billion people globally and differs from cow milk in protein composition. Identifying bioactive peptides specific to buffalo milk could inform the development of functional foods, nutraceuticals, or dairy products with validated health benefits — particularly relevant in South Asian and Mediterranean regions where buffalo milk is a dietary staple.","specificNumbers":"","methodology":"Buffalo milk protein sequences were analyzed for similarity to cow milk proteins. In silico proteolysis simulated enzymatic digestion to generate theoretical peptides. Candidates were screened using the BIOPEP-UWM database (A values), PeptideRanker, Innovagen, peptide-cutter, and molecular docking. Selected peptides were synthesized and tested in vitro for ACE and DPP-IV inhibition. Lineweaver-Burk plots were used to determine inhibition type (competitive vs. mixed).","limitations":"The IC50 values are in the micromolar range, which is considerably weaker than pharmaceutical ACE inhibitors (nanomolar) and DPP-IV inhibitors (nanomolar). Bioavailability — whether these peptides survive digestion and reach target enzymes in active form — was not assessed. No in vivo or clinical testing was performed. The in silico proteolysis may not accurately reflect actual enzymatic digestion conditions in the human gut. The study explicitly states it does not involve any clinical trial."},{"rthcId":"RPEP-06923","title":"Nociceptin/Orphanin FQ Opioid Peptide-Receptor Expression in the Endometriosis-Associated Nerve Fibers-Possible Treatment Option?","authors":"Guan, Qihui; Velho, Renata Voltolini; Jordan, Alice; Pommer, Sabrina; Radde, Irene; Sehouli, Jalid; Mechsner, Sylvia","year":2023,"journal":"Cells, 12(10)","doi":"10.3390/cells12101395","pmid":"37408230","tags":["nociceptin","opioid-peptides"],"studyType":"observational-human-tissue","evidenceStrength":"moderate","keyFinding":"NOP receptor expression was detected on peritoneal nerve fibers in both endometriosis patients and healthy controls, but expression was increased in endometriosis-associated nerve fibers. NOP frequently colocalized with substance P, CGRP, tyrosine hydroxylase, and VIP-positive nerve fibers, indicating it is expressed on both sensory (pain-transmitting) and autonomic nerve fibers.\n\nThis is the first study to characterize NOP receptor expression specifically in endometriosis-associated nerve fibers, establishing a molecular basis for testing NOP agonists as analgesics in this condition.","whyItMatters":"Endometriosis affects millions of women and chronic pelvic pain is one of its most debilitating symptoms. Current pain management options — NSAIDs, hormonal therapies, surgery — are often insufficient. The nociceptin/NOP system is distinct from traditional opioid pathways and doesn't carry the same addiction risk. Finding NOP receptors on the very nerve fibers responsible for endometriosis pain suggests a highly targeted treatment approach that could offer relief without the drawbacks of conventional opioids.","specificNumbers":"n=94 (73 EM, 21 controls); NOP colocalized with SP, CGRP, TH, VIP; NOP expression increased in EM-associated nerve fibers","methodology":"Laparoscopically excised peritoneal tissue from 94 symptomatic women (73 with endometriosis, 21 controls) was analyzed using immunohistochemistry for NOP, PGP9.5, substance P, CGRP, tyrosine hydroxylase, and VIP. Colocalization of NOP with sensory and autonomic nerve fiber markers was assessed.","limitations":"Observational tissue study only — no drug tested. Immunohistochemistry shows presence, not function. Correlation between NOP expression and pain severity not assessed. No NOP agonist intervention."},{"rthcId":"RPEP-06924","title":"Dulaglutide Improves Gliosis and Suppresses Apoptosis/Autophagy Through the PI3K/Akt/mTOR Signaling Pathway in Vascular Dementia Rats.","authors":"Guan, Tianyuan; Xiao, Yining; Xie, Xiaohua; Meng, Nan; Qi, Qianqian; Xu, Jing; Jiang, Xin; Zhang, Zhe; Teng, Zhenjie; Lv, Peiyuan","year":2023,"journal":"Neurochemical research, 48(5), 1561-1579","doi":"10.1007/s11064-022-03853-0","pmid":"36571662","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In vascular dementia rats, dulaglutide treatment produced multiple neuroprotective effects:\n\n- Cognitive improvement: Morris water maze testing showed significantly reduced cognitive decline\n- Neuroprotection: Neuronal damage in the hippocampus was significantly alleviated\n- Reduced gliosis: Microglial and astrocyte proliferation (inflammation markers) were decreased\n- Anti-apoptotic effects: BCL2/BAX ratio and cleaved caspase-3 indicated reduced cell death\n- Autophagy regulation: P62, LC3B, and Beclin-1 markers showed normalized autophagy\n- Mechanism: PI3K/Akt/mTOR signaling pathway was activated, with the mTOR repressor Deptor downregulated\n\nRNA sequencing confirmed that mTOR pathway genes were significantly enriched among differentially expressed genes in the dulaglutide group.","whyItMatters":"Vascular dementia is the second most common form of dementia after Alzheimer's disease and currently has no approved disease-modifying treatments. The finding that dulaglutide — an already FDA-approved diabetes drug — can protect against vascular dementia in animal models is significant because drug repurposing can dramatically shorten the path to clinical use. This adds to mounting evidence that GLP-1 drugs have neuroprotective effects beyond their metabolic actions, with potential applications across multiple forms of dementia.","specificNumbers":"","methodology":"Vascular dementia was induced in Sprague-Dawley rats by bilateral carotid artery occlusion. Cognitive function was assessed using the Morris water maze (learning/memory) and open-field test (anxiety behavior). Brain tissue was analyzed using HE staining and immunofluorescence for neuronal damage and glial cell proliferation. Western blotting measured apoptosis and autophagy markers plus PI3K/Akt/mTOR pathway activation. RNA sequencing with KEGG pathway analysis identified differentially expressed genes and enriched pathways.","limitations":"This is a preclinical rat study using an acute surgical model of vascular dementia, which may not fully replicate the chronic, progressive nature of human vascular dementia. Only one dose of dulaglutide was tested, so the optimal dosing regimen is unknown. The bilateral carotid artery occlusion model is severe and does not represent the typical gradual small vessel disease that causes most human vascular dementia. Long-term safety and efficacy of brain-targeted GLP-1RA treatment were not assessed."},{"rthcId":"RPEP-06925","title":"Discovery of Sulanemadlin (ALRN-6924), the First Cell-Permeating, Stabilized α-Helical Peptide in Clinical Development.","authors":"Guerlavais, Vincent; Sawyer, Tomi K; Carvajal, Luis; Chang, Yong S; Graves, Bradford; Ren, Jian-Guo; Sutton, David; Olson, Karen A; Packman, Kathryn; Darlak, Krzysztof; Elkin, Carl; Feyfant, Eric; Kesavan, Kamala; Gangurde, Pranoti; Vassilev, Lyubomir T; Nash, Huw M; Vukovic, Vojislav; Aivado, Manuel; Annis, D Allen","year":2023,"journal":"Journal of medicinal chemistry, 66(14), 9401-9417","doi":"10.1021/acs.jmedchem.3c00623","pmid":"37439511","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06926","title":"Proteomic analysis of salivary inflammatory biomarkers of developmental gingival enlargements in patients with West and Noonan syndromes: a preliminary pilot single-center retrospective study.","authors":"Guglielmi, F; Kirschner, F; Staderini, E; Iavarone, F; Fiorino, A; Gallenzi, P","year":2023,"journal":"European review for medical and pharmacological sciences, 27(22), 11093-11102","doi":"10.26355/eurrev_202311_34478","pmid":"38039040","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06927","title":"Safety and effectiveness of dulaglutide in Chinese adults with type 2 diabetes mellitus in a real-world setting: A prospective, observational post-marketing study.","authors":"Guo, Lixin; Li, Li; Yu, Qiurong; Wang, Na; Chen, Jun; Xi, Yue; Wang, Huan; Wang, Yihua; Xu, Jiawei","year":2023,"journal":"Diabetes, obesity & metabolism, 25(12), 3578-3588","doi":"10.1111/dom.15252","pmid":"37612876","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 3,291 Chinese adults with T2DM prescribed dulaglutide in routine clinical practice (46 hospitals, 2020-2021):\n\n- HbA1c: -1.65% from baseline at 24 weeks (p<0.001)\n- Body weight: -2.62 kg from baseline at 24 weeks (p<0.001)\n- TEAEs: Reported in 40.5% — nausea (5.9%), diarrhea (5.6%), decreased appetite (5.4%)\n- Serious AEs: 4.9% of patients\n- Treatment discontinuation due to AEs: 6.4%\n\nGreater HbA1c reductions seen in patients with:\n- T2DM duration ≤5 years (p=0.002)\n- Baseline HbA1c ≥8.5% (p<0.001)\n- No atherosclerotic cardiovascular disease (p=0.002)","whyItMatters":"Clinical trial data doesn't always predict real-world performance, especially across different ethnic populations. This first GLP-1 RA real-world study in Chinese patients confirms dulaglutide works effectively in everyday clinical practice in China — important given the country's enormous diabetes burden (140+ million people).","specificNumbers":"","methodology":"Prospective, observational, post-marketing study at 46 hospitals in China. Adults with T2DM prescribed dulaglutide in routine practice were followed for up to 24 weeks. Primary endpoint: TEAE and serious AE incidence. Exploratory endpoints: HbA1c and body weight changes. Post hoc subgroup analyses and multivariate regression identified predictors of response.","limitations":"This is an observational study without a control group, so improvements cannot be definitively attributed to dulaglutide alone. Not all patients completed the 24-week follow-up. HbA1c and weight data were patient-reported, which may introduce measurement variability. The study was industry-sponsored (Eli Lilly). Only dulaglutide was studied; comparisons with other GLP-1 RAs were not possible."},{"rthcId":"RPEP-06928","title":"Discovery of ecnoglutide - A novel, long-acting, cAMP-biased glucagon-like peptide-1 (GLP-1) analog.","authors":"Guo, Wanjun; Xu, Zheng; Zou, Haixia; Li, Feng; Li, Yao; Feng, Jing; Zhu, Zhiyi; Zheng, Qing; Zhu, Rui; Wang, Bin; Li, Yan; Hao, Sujuan; Qin, Hong; Jones, Catherine L; Adegbite, Eric; Telusca, Libnir; Fenaux, Martijn; Zhong, Weidong; Junaidi, Mohammed K; Xu, Susan; Pan, Hai","year":2023,"journal":"Molecular metabolism, 75, 101762","doi":"10.1016/j.molmet.2023.101762","pmid":"37364710","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06929","title":"Stimuli-Responsive Self-Assembly Disassembly in Peptide Amphiphiles to Endow Block-co-Fibers and Tunable Piezoelectric Response.","authors":"Gupta, Deepika; Gupta, Varun; Nath, Debasish; Miglani, Chirag; Mandal, Dipankar; Pal, Asish","year":2023,"journal":"ACS applied materials & interfaces, 15(21), 25110-25121","doi":"10.1021/acsami.2c05469","pmid":"35767722","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06930","title":"Differential Influences of Endogenous and Exogenous Sensory Neuropeptides on the ATP Metabolism by Soluble Ectonucleotidases in the Murine Bladder Lamina Propria.","authors":"Gutierrez Cruz, Alejandro; Aresta Branco, Mafalda S L; Borhani Peikani, Mahsa; Mutafova-Yambolieva, Violeta N","year":2023,"journal":"International journal of molecular sciences, 24(21)","doi":"10.3390/ijms242115650","pmid":"37958631","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06931","title":"Does Therapy with Glucagon-like Peptide 1 Receptor Agonists Have an Effect on Biochemical Markers of Metabolic-Dysfunction-Associated Steatotic Liver Disease (MASLD)? Pleiotropic Metabolic Effect of Novel Antidiabetic Drugs in Patients with Diabetes-Interventional Study.","authors":"Hachuła, Marcin; Kosowski, Michał; Basiak, Marcin; Okopień, Bogusław","year":2023,"journal":"Pharmaceuticals (Basel, Switzerland), 16(9)","doi":"10.3390/ph16091190","pmid":"37764998","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06932","title":"An Effective Peptide-Based Platform for Efficient Exosomal Loading and Cellular Delivery of a microRNA.","authors":"Hade, Mangesh D; Suire, Caitlin N; Suo, Zucai","year":2023,"journal":"ACS applied materials & interfaces, 15(3), 3851-3866","doi":"10.1021/acsami.2c20728","pmid":"36638205","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06933","title":"Evaluating the efficacy of CGRP mAbs and gepants for the preventive treatment of migraine: A systematic review and network meta-analysis of phase 3 randomised controlled trials.","authors":"Haghdoost, Faraidoon; Puledda, Francesca; Garcia-Azorin, David; Huessler, Eva-Maria; Messina, Roberta; Pozo-Rosich, Patricia","year":2023,"journal":"Cephalalgia : an international journal of headache, 43(4), 3331024231159366","doi":"10.1177/03331024231159366","pmid":"36855951","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06934","title":"Adjusting Heterodimeric Coiled-Coils (K/E Zipper) to Connect Autophagy-Inducing Peptide with Cell-Penetrating Peptide.","authors":"Hakata, Yoshiyuki; Yamashita, Kazuma; Hashimoto, Sonoko; Ohtsuki, Takashi; Miyazawa, Masaaki; Kitamatsu, Mizuki","year":2023,"journal":"Pharmaceutics, 15(4)","doi":"10.3390/pharmaceutics15041048","pmid":"37111533","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Coiled-coil molecular zippers with 3 and 4 repeating units (K/E zipper n=3 and n=4) formed stable 1:1 hybrid complexes between the autophagy-inducing peptide and the cell-penetrating peptide. Both successfully delivered the functional peptide into cells.\n\nInterestingly, the 3-repeat zipper induced autophagy more intensively than the 4-repeat version, suggesting that the optimal biological activity depends on a balance between how strongly the zipper holds together and how readily it releases the functional peptide inside the cell. Shorter zippers (n=1 and n=2) did not form stable hybrids. None of the peptides or zippers showed significant cytotoxicity.","whyItMatters":"Many promising therapeutic peptides fail because they cannot get inside cells where they need to work. This modular zipper delivery system is significant because it allows researchers to fine-tune how peptides are transported into cells and released, without chemically modifying the therapeutic peptide itself. The approach could be adapted for delivering many different types of functional peptides beyond autophagy inducers.","specificNumbers":"","methodology":"The researchers synthesized autophagy-inducing peptides conjugated to one half of a coiled-coil zipper (K strand) of varying lengths (1-4 repeats), paired with cell-penetrating peptides attached to the complementary half (E strand). They used fluorescence spectroscopy to assess hybrid formation stability, cell delivery assays to confirm intracellular uptake, autophagy assays to measure biological activity, and cytotoxicity assays to confirm safety.","limitations":"This was an in vitro cell culture study, so it is unknown whether the zipper system would work in living organisms where factors like blood stability, immune recognition, and tissue penetration come into play. The study tested only one functional peptide (the autophagy inducer), so generalizability to other therapeutic peptides is assumed but not proven. Quantitative data on autophagy levels and delivery efficiency were limited to relative comparisons."},{"rthcId":"RPEP-06935","title":"Smart design of universally decorated nanoparticles for drug delivery applications driven by active transport.","authors":"Halbi, Gal; Fayer, Itay; Aranovich, Dina; Gat, Shachar; Pavan, Mariela J; Nachmias, Dikla; Sanchez, Daniel Sevilla; Brik, Ashraf; Granek, Rony; Bernheim-Groswasser, Anne","year":2023,"journal":"The European physical journal. E, Soft matter, 46(9), 74","doi":"10.1140/epje/s10189-023-00331-5","pmid":"37653248","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06936","title":"Signaling mechanism of growth hormone-releasing hormone receptor.","authors":"Halmos, Gabor; Szabo, Zsuzsanna; Juhasz, Eva; Schally, Andrew V","year":2023,"journal":"Vitamins and hormones, 123, 1-26","doi":"10.1016/bs.vh.2023.06.004","pmid":"37717982","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06937","title":"Self-Assembly, Bioactivity, and Nanomaterials Applications of Peptide Conjugates with Bulky Aromatic Terminal Groups.","authors":"Hamley, Ian W","year":2023,"journal":"ACS applied bio materials, 6(2), 384-409","doi":"10.1021/acsabm.2c01041","pmid":"36735801","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06938","title":"Involvement of ASIC3 and Substance P in Therapeutic Ultrasound-Mediated Analgesia in Mouse Models of Fibromyalgia.","authors":"Han, Der-Sheng; Lee, Cheng-Han; Shieh, Yih-Dar; Chang, Ke-Vin; Lin, Shing-Hong; Chu, Ya-Cherng; Wang, Jaw-Lin; Chen, Chih-Cheng","year":2023,"journal":"The journal of pain, 24(8), 1493-1505","doi":"10.1016/j.jpain.2023.04.003","pmid":"37054767","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06939","title":"Antimicrobial peptides do not directly contribute to aging in Drosophila, but improve lifespan by preventing dysbiosis.","authors":"Hanson, Mark A; Lemaitre, Bruno","year":2023,"journal":"Disease models & mechanisms, 16(4)","doi":"10.1242/dmm.049965","pmid":"36847474","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Using isogenic AMP gene deletions in Drosophila, no individual antimicrobial peptide had a major effect on lifespan, with the possible exception of Defensin. However, ΔAMP14 flies lacking seven AMP gene families showed significantly reduced lifespan.\n\nThe lifespan reduction was traced to microbiome dysbiosis: aged ΔAMP14 flies had increased bacterial loads in their food. Critically, raising ΔAMP14 flies under germ-free conditions restored their lifespan, proving the reduced lifespan was due to loss of microbial control, not a direct role of AMPs in aging or inflammation.","whyItMatters":"AMPs increase with age in many organisms, fueling the hypothesis that they drive age-related inflammatory diseases ('inflammaging'). This study overturns that narrative by showing AMPs are not causing aging — they're fighting it by keeping gut bacteria under control. This reframes how we think about immune peptides in aging and highlights the importance of maintaining antimicrobial defenses throughout life.","specificNumbers":"","methodology":"The researchers created an isogenic set of Drosophila with deletions in individual AMP genes and a comprehensive ΔAMP14 line lacking seven AMP gene families. They measured lifespan in conventional and germ-free conditions, assessed bacterial loads in aged flies' food, and compared the effects of individual versus collective AMP loss on longevity.","limitations":"The study was conducted in Drosophila, and the findings may not directly translate to mammalian aging. The microbiome of fruit flies is simpler than the human gut microbiome. The study focused on lifespan as the primary outcome and did not extensively characterize other age-related phenotypes. The possible exception of Defensin's individual effect needs further investigation."},{"rthcId":"RPEP-06940","title":"Enhancing Antisense Oligonucleotide-Based Therapeutic Delivery with DG9, a Versatile Cell-Penetrating Peptide.","authors":"Haque, Umme Sabrina; Yokota, Toshifumi","year":2023,"journal":"Cells, 12(19)","doi":"10.3390/cells12192395","pmid":"37830609","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06941","title":"Impact of Liraglutide to Semaglutide Conversion on Glycemic Control and Cost Savings at a Veterans Affairs Medical Center.","authors":"Hardin, Maiah; Adanse, Fiona; Schexnayder, Chandler; Malveaux, Janeca; Agbahiwe, Sylvester","year":2023,"journal":"Federal practitioner : for the health care professionals of the VA, DoD, and PHS, 40(Suppl 6), S24-S30","doi":"10.12788/fp.0413","pmid":"38812588","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 304 veterans converted from liraglutide (0.6 or 1.2 mg daily) to semaglutide (0.25 mg weekly, titrated to 0.5 mg weekly):\n\n- Mean HbA1c decreased significantly from 8.1% (SD 1.5) to 7.6% (SD 1.4) at 3–12 months (P significant)\n- Mean baseline blood glucose: 187.4 mg/dL (SD 44.2)\n- Mean baseline body weight: 112.9 kg (SD 23.0); significant weight loss observed (P < 0.001)\n- Minimal changes to antihyperglycemic regimens were needed\n- Cost savings exceeded $400,000 from the conversion\n- Common adverse effects: hypoglycemia and gastrointestinal intolerance","whyItMatters":"With GLP-1 drugs being expensive, finding ways to optimize both clinical outcomes and costs is important for healthcare systems. This study shows that switching from an older daily GLP-1 peptide to a newer weekly one can improve blood sugar control, promote weight loss, and generate significant cost savings — a win across the board.","specificNumbers":"","methodology":"Retrospective chart review of veterans without retinopathy treated at the Michael E. DeBakey VA Medical Center between March and November 2021. Patients on liraglutide 0.6 or 1.2 mg daily were converted to semaglutide 0.25 mg weekly (titrated to 0.5 mg after 4 weeks). HbA1c values were compared at baseline and 3–12 months post-conversion. Cost savings were calculated using outpatient pharmacy data.","limitations":"This was a retrospective study without a control group, making it impossible to determine whether improvements were due to the drug switch or other factors. The conversion used relatively low semaglutide doses (0.5 mg), not the maximum approved dose (2.0 mg for diabetes, 2.4 mg for weight loss). The VA patient population (predominantly male veterans) may not be representative of the general population. A full cost-effectiveness analysis was not conducted."},{"rthcId":"RPEP-06942","title":"Endothelial Function in Patients with Multiple Sclerosis: The Role of GLP-1 Agonists, Lipoprotein Subfractions, and Redox Balance.","authors":"Hardonova, Miroslava; Siarnik, Pavel; Sivakova, Monika; Sucha, Bianka; Penesova, Adela; Radikova, Zofia; Havranova, Andrea; Imrich, Richard; Vlcek, Miroslav; Zitnanova, Ingrid; Krastev, Georgi; Kiacikova, Maria; Kollar, Branislav; Turcani, Peter","year":2023,"journal":"International journal of molecular sciences, 24(13)","doi":"10.3390/ijms241311162","pmid":"37446338","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06943","title":"Cell-Penetrating Peptidic GRP78 Ligand-Conjugated Iron Oxide Magnetic Nanoparticles for Tumor-Targeted Doxorubicin Delivery and Imaging.","authors":"Hasani, Mahdiyeh; Jafari, Samira; Akbari Javar, Hamid; Abdollahi, Hossein; Rashidzadeh, Hamid","year":2023,"journal":"ACS applied bio materials, 6(3), 1019-1031","doi":"10.1021/acsabm.2c00897","pmid":"36862384","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06944","title":"In Vitro and In Silico Studies on Angiotensin I-Converting Enzyme Inhibitory Peptides Found in Hydrophobic Domains of Porcine Elastin.","authors":"Hatakenaka, Toshiya; Kato, Tamaki; Okamoto, Kouji","year":2023,"journal":"Molecules (Basel, Switzerland), 28(8)","doi":"10.3390/molecules28083337","pmid":"37110571","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06945","title":"Folic acid-modified reverse micelle-lipid nanocapsules overcome intestinal barriers and improve the oral delivery of peptides.","authors":"He, Jibiao; Ding, Ruihuan; Tao, Yuping; Zhao, Zhenyu; Yuan, Ranran; Zhang, Houqian; Wang, Aiping; Sun, Kaoxiang; Li, Youxin; Shi, Yanan","year":2023,"journal":"Drug delivery, 30(1), 2181744","doi":"10.1080/10717544.2023.2181744","pmid":"36855953","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06946","title":"Enhanced Tumor Targeting and Penetration of Proteolysis-Targeting Chimeras through iRGD Peptide Conjugation: A Strategy for Precise Protein Degradation in Breast Cancer.","authors":"He, Shipeng; Fang, Yuxin; Wu, Minghao; Zhang, Peifeng; Gao, Fei; Hu, Honggang; Sheng, Chunquan; Dong, Guoqiang","year":2023,"journal":"Journal of medicinal chemistry, 66(24), 16828-16842","doi":"10.1021/acs.jmedchem.3c01539","pmid":"38055861","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The iRGD-PROTAC conjugate (iPR) was created by linking the tumor-penetrating cyclic peptide iRGD (CRGDK/RGPD/EC) to a BRD4-targeting PROTAC through a glutathione (GSH)-responsive linker that releases the active drug inside tumor cells.\n\nCompared to the unconjugated PROTAC, the iRGD-PROTAC conjugate showed enhanced water solubility, improved tumor-targeting capability, and deeper penetration within breast cancer tissues. These improvements translated to increased anti-breast cancer efficacy in both animal models and patient-derived organoids, validating the concept that peptide-guided delivery can overcome key limitations of PROTAC-based cancer therapies.","whyItMatters":"PROTACs represent one of the most exciting advances in cancer drug development, but their clinical potential has been limited by poor drug-like properties — especially difficulty reaching tumor cells deep within solid tumors. By using a tumor-penetrating peptide as a delivery vehicle, this study addresses a major bottleneck in PROTAC therapeutics and demonstrates a modular strategy that could potentially be applied to PROTACs targeting many different cancer-driving proteins.","specificNumbers":"","methodology":"The researchers designed and synthesized an iRGD-PROTAC conjugate using a GSH-responsive cleavable linker. They evaluated water solubility, tumor-targeting ability, and tissue penetration through in vitro and in vivo experiments. Anti-cancer efficacy was tested in breast cancer animal models and patient-derived organoids (3D tumor tissue cultures grown from patient samples). The BRD4 PROTAC component was chosen as a proof-of-concept target for protein degradation.","limitations":"This is a proof-of-concept study targeting only one protein (BRD4) in breast cancer. The approach needs to be validated with other PROTAC targets and cancer types. While patient-derived organoids provide better translational relevance than cell lines alone, they still differ from tumors in patients. Long-term toxicity, pharmacokinetics, and the stability of the GSH-responsive linker in circulation were not fully characterized in the abstract. Human clinical trials would be needed to confirm therapeutic benefit."},{"rthcId":"RPEP-06947","title":"A novel peptide derived from Haematococcus pluvialis residue exhibits anti-aging activity in Caenorhabditis elegans via the insulin/IGF-1 signaling pathway.","authors":"He, Wanshi; Xie, Junting; Xia, Zenghui; Chen, Xiaoyan; Xiao, Jie; Cao, Yong; Liu, Xiaojuan","year":2023,"journal":"Food & function, 14(12), 5576-5588","doi":"10.1039/d3fo00383c","pmid":"37232088","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06948","title":"Cold Exposure and Oral Delivery of GLP-1R Agonists by an Engineered Probiotic Yeast Strain Have Antiobesity Effects in Mice.","authors":"Hedin, Karl Alex; Zhang, Hongbin; Kruse, Vibeke; Rees, Vanessa Emily; Bäckhed, Fredrik; Greiner, Thomas U; Vazquez-Uribe, Ruben; Sommer, Morten Otto Alexander","year":2023,"journal":"ACS synthetic biology, 12(11), 3433-3442","doi":"10.1021/acssynbio.3c00455","pmid":"37827516","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06949","title":"Tirzepatide Reduces Appetite, Energy Intake, and Fat Mass in People With Type 2 Diabetes.","authors":"Heise, Tim; DeVries, J Hans; Urva, Shweta; Li, Jing; Pratt, Edward J; Thomas, Melissa K; Mather, Kieren J; Karanikas, Chrisanthi A; Dunn, Julia; Haupt, Axel; Milicevic, Zvonko; Coskun, Tamer","year":2023,"journal":"Diabetes care, 46(5), 998-1004","doi":"10.2337/dc22-1710","pmid":"36857477","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tirzepatide 15 mg produced significantly greater body weight and fat mass reductions compared to both semaglutide 1 mg and placebo over 28 weeks in type 2 diabetes patients. Both tirzepatide and semaglutide significantly reduced appetite versus placebo, but appetite scores and energy intake reductions during ad libitum lunch did not differ between the two drugs.\n\nThis surprising finding — that tirzepatide and semaglutide suppress appetite equally but tirzepatide produces more weight loss — suggests tirzepatide's superior weight loss involves mechanisms beyond appetite reduction, possibly including effects on 24-hour energy intake, substrate utilization, or energy expenditure.","whyItMatters":"Tirzepatide consistently produces more weight loss than semaglutide in clinical trials, but why has been unclear. This study reveals that appetite suppression alone doesn't explain the difference — both drugs reduce hunger similarly. This means the dual GIP/GLP-1 mechanism of tirzepatide must provide additional metabolic benefits, possibly through increased fat burning or energy expenditure, that go beyond simply eating less. Understanding these mechanisms could inform the development of even more effective peptide-based obesity treatments.","specificNumbers":"N=117 (45 tirzepatide, 44 semaglutide, 28 placebo) · 28 weeks · Greater fat mass reduction with tirzepatide · Equal appetite suppression between drugs · Energy intake difference insufficient to explain weight outcomes","methodology":"Secondary analysis of a randomized, double-blind, parallel-arm Phase 2 study. Type 2 diabetes patients received tirzepatide 15 mg (n=45), semaglutide 1 mg (n=44), or placebo (n=28) for 28 weeks. Body composition was assessed (fat mass vs lean mass). Appetite was measured by visual analog scales. Energy intake was measured during ad libitum lunch meals.","limitations":"This is a secondary analysis of a trial not primarily designed for these endpoints. The sample size is small (117 total). Energy intake was only measured during a single ad libitum lunch, not over 24 hours — other meals may differ. Semaglutide was dosed at 1 mg (not 2.4 mg, the obesity dose), so the comparison may not reflect maximal semaglutide efficacy. The mechanisms explaining tirzepatide's greater weight loss were not identified, only that appetite reduction isn't sufficient."},{"rthcId":"RPEP-06950","title":"Real world outcomes in patients with neuroendocrine tumor receiving peptide receptor radionucleotide therapy.","authors":"Hentzen, Stijn; Mehta, Kathan; Al-Rajabi, Raed Moh'd Taiseer; Saeed, Anwaar; Baranda, Joaquina Celebre; Williamson, Stephen K; Sun, Weijing; Kasi, Anup","year":2023,"journal":"Exploration of targeted anti-tumor therapy, 4(3), 396-405","doi":"10.37349/etat.2023.00141","pmid":"37455826","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06951","title":"Aquiluscidin, a Cathelicidin from Crotalus aquilus, and the Vcn-23 Derivative Peptide, Have Anti-Microbial Activity against Gram-Negative and Gram-Positive Bacteria.","authors":"Hernández-Arvizu, Edwin Esaú; Silis-Moreno, Teresa Monserrat; García-Arredondo, José Alejandro; Rodríguez-Torres, Angelina; Cervantes-Chávez, José Antonio; Mosqueda, Juan","year":2023,"journal":"Microorganisms, 11(11)","doi":"10.3390/microorganisms11112778","pmid":"38004789","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"From transcripts obtained from the skin and oral mucosa of Crotalus aquilus, researchers identified the first cathelicidin-like peptide from this species. The peptide precursor contained a signal peptide, a 101-amino-acid conserved cathelin domain, an anionic region, and a 34-amino-acid mature peptide (Aquiluscidin/Aq-CATH).\n\nBoth Aq-CATH and its shorter 23-amino-acid derivative Vcn-23 demonstrated potent broad-spectrum antibacterial activity with MIC values of 2-8 µg/mL against all tested Gram-positive and Gram-negative bacteria. At concentrations up to 50 µM, neither peptide showed significant hemolytic activity. However, cytotoxicity testing showed cell viability dropped below 65% at 25 µM, indicating a window between antimicrobial and cytotoxic concentrations that needs optimization.","whyItMatters":"Venomous animals are a rich source of bioactive peptides that evolution has optimized over millions of years. Cathelicidins from reptiles are particularly interesting because reptiles live in pathogen-rich environments and rely heavily on innate immunity. Discovering new antimicrobial peptides from previously unstudied species like Crotalus aquilus expands the pool of potential candidates for antibiotic development at a time when drug-resistant infections are a growing global crisis.","specificNumbers":"","methodology":"cDNA was cloned and sequenced from transcripts of Crotalus aquilus skin and oral mucosa, yielding a 566-base-pair sequence. Bioinformatic analysis predicted the peptide's structural domains. The full-length mature peptide (Aq-CATH, 34 amino acids) and a derived shorter peptide (Vcn-23, 23 amino acids) were chemically synthesized. Antimicrobial activity was evaluated through in vitro MIC assays against multiple Gram-positive and Gram-negative bacterial species. Hemolytic activity and cytotoxicity were assessed to evaluate safety.","limitations":"This is an in vitro study only — no animal infection models were used to test in vivo efficacy. The cytotoxicity data (cell viability <65% at 25 µM) suggests a relatively narrow therapeutic window that would need improvement for clinical use. The specific bacterial strains tested and whether they included drug-resistant isolates are not detailed in the abstract. Stability, pharmacokinetics, and mechanism of action were not investigated. The study comes from a single species of rattlesnake."},{"rthcId":"RPEP-06952","title":"β-defensin 2 synthesized by a cell-free protein synthesis system and encapsulated in liposomes inhibits adhesion of Porphyromonas gingivalis to oral epithelial cells.","authors":"Hiroshima, Yuka; Kido, Jun-Ichi; Kido, Rie; Yoshida, Kaya; Bando, Mika; Kajimoto, Kazuaki; Yumoto, Hiromichi; Shinohara, Yasuo","year":2023,"journal":"Odontology, 111(4), 830-838","doi":"10.1007/s10266-023-00789-x","pmid":"36745267","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06953","title":"Case report: Peptide receptor radioligand therapy in metastatic pediatric neuroendocrine tumors.","authors":"Hlongwa, Khanyisile; Kolade, Olumayowa; Alnabulsi, Abdulilah; Steyn, Rachelle; Brink, Anita; Prasad, Vikas; More, Stuart","year":2023,"journal":"Frontiers in nuclear medicine, 3, 1193880","doi":"10.3389/fnume.2023.1193880","pmid":"39355026","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06954","title":"No virologic resistance to bulevirtide monotherapy detected in patients through 24 weeks treatment in phase II and III clinical trials for chronic hepatitis delta.","authors":"Hollnberger, Julius; Liu, Yang; Xu, Simin; Chang, Silvia; Martin, Ross; Manhas, Savrina; Aeschbacher, Thomas; Han, Bin; Yazdi, Tahmineh; May, Lindsey; Han, Dong; Shornikov, Alex; Flaherty, John; Manuilov, Dmitry; Suri, Vithika; Asselah, Tarik; Lampertico, Pietro; Wedemeyer, Heiner; Aleman, Soo; Richards, Christopher; Mateo, Roberto; Maiorova, Evguenia; Cihlar, Tomas; Mo, Hongmei; Urban, Stephan","year":2023,"journal":"Journal of hepatology, 79(3), 657-665","doi":"10.1016/j.jhep.2023.04.027","pmid":"37120031","tags":[],"studyType":"clinical-trial","evidenceStrength":"high","keyFinding":"In the first-ever viral resistance analysis of bulevirtide (a lipopeptide entry inhibitor for hepatitis delta virus), no drug resistance was detected in any patient through 24 weeks of treatment. Deep sequencing of the drug's target regions found no amino acid changes associated with reduced sensitivity to bulevirtide — not in the 20 non-responders, not in the 1 patient with virologic breakthrough, and not in any baseline samples.\n\nPhenotypic testing of 116 baseline samples showed similar bulevirtide susceptibility (EC50 values) across responders, partial responders, and non-responders regardless of any HBV or HDV genetic variations present. This demonstrates that bulevirtide has a high barrier to resistance, and that non-response to treatment is caused by other unknown mechanisms — not viral escape from the drug.","whyItMatters":"Hepatitis delta is the most severe form of viral hepatitis, and bulevirtide is the first drug specifically approved to treat it. Drug resistance is the biggest fear with any antiviral therapy — if the virus mutates to evade the drug, treatment fails. This study shows bulevirtide has a remarkably high genetic barrier to resistance, making it suitable for long-term use. Since hepatitis delta requires prolonged treatment, this resistance profile is crucial for clinical confidence.","specificNumbers":"n=21 analyzed (20 non-responders + 1 virologic breakthrough) · 116 baseline samples phenotyped · 24-week treatment period · 0 resistance mutations detected · EC50 values similar across all response categories · Variants found in 14 patients — none reduced drug sensitivity","methodology":"Researchers performed deep sequencing on the bulevirtide-target regions of HBV PreS1 and HDV HDAg genes at baseline and week 24 in 21 patients from the phase II MYR202 and phase III MYR301 trials who either didn't respond adequately or had virologic breakthrough. In vitro phenotypic susceptibility testing measured bulevirtide EC50 values across 116 baseline samples from patients with all response categories.","limitations":"The analysis covered only 24 weeks — longer treatment periods could potentially select for resistance mutations not seen in this timeframe. Only 21 non-responder/breakthrough patients were analyzed by deep sequencing. The finding that non-response isn't caused by resistance raises new questions about what does cause it. This was a monotherapy analysis; combination therapy regimens may have different resistance dynamics."},{"rthcId":"RPEP-06955","title":"A Review of Protein- and Peptide-Based Chemical Conjugates: Past, Present, and Future.","authors":"Holz, Emily; Darwish, Martine; Tesar, Devin B; Shatz-Binder, Whitney","year":2023,"journal":"Pharmaceutics, 15(2)","doi":"10.3390/pharmaceutics15020600","pmid":"36839922","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06956","title":"Is abaloparatide more efficacious on increasing bone mineral density than teriparatide for women with postmenopausal osteoporosis? An updated meta-analysis.","authors":"Hong, Pan; Liu, Ruikang; Rai, Saroj; Liu, JiaJia; Zhou, YeMing; Zheng, Yu; Li, Jin","year":2023,"journal":"Journal of orthopaedic surgery and research, 18(1), 116","doi":"10.1186/s13018-023-03595-x","pmid":"36797767","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In a meta-analysis of four studies (16 subgroups) from head-to-head RCTs, abaloparatide showed significantly greater BMD improvements than teriparatide at the femoral neck (WMD = 1.58, 95% CI 0.52–2.63) and total hip (WMD = 1.46, 95% CI 0.59–2.32) — both rated high-quality evidence by GRADE criteria.\n\nAll BMD parameters at 24 weeks favored abaloparatide except lumbar spine. The incidence of hypercalcemia was 51% lower with abaloparatide compared to teriparatide. No significant differences were found in serious adverse events or deaths between the two drugs. However, compared to placebo, abaloparatide was associated with higher risks of nausea and palpitations. Fracture data was insufficient for meaningful analysis.","whyItMatters":"For the millions of postmenopausal women with osteoporosis, choosing between the two available bone-building peptide drugs has been difficult due to limited head-to-head data. This meta-analysis provides the most comprehensive comparison to date, suggesting abaloparatide may offer an edge at the hip — the most clinically important fracture site — while also being associated with less hypercalcemia, a meaningful safety advantage.","specificNumbers":"","methodology":"Systematic review and meta-analysis searching Medline, Embase, Web of Science, Cochrane, and ClinicalTrials.gov through September 2022. Only randomized controlled trials with direct head-to-head comparisons of abaloparatide vs teriparatide were included. Evidence quality was assessed using the GRADE framework. Outcomes included BMD change from baseline and adverse event rates.","limitations":"Only four studies met inclusion criteria, all from manufacturer-sponsored trials, which introduces potential bias. Fracture data was insufficient for analysis — and fracture prevention, not BMD alone, is the ultimate clinical outcome. The meta-analysis was limited to postmenopausal women, so results may not apply to men or premenopausal osteoporosis. Most comparisons relied on post hoc analyses of RCTs rather than pre-specified head-to-head designs."},{"rthcId":"RPEP-06957","title":"Glycemic and Economic Outcomes in Elderly Patients with Type 2 Diabetes Initiating Dulaglutide Versus Basal Insulin in a Real-World Setting in the United States: The DISPEL-Advance Study.","authors":"Hoog, Meredith; Paczkowski, Rosirene; Huang, Ahong; Halpern, Rachel; Buysman, Erin; Stackland, Sydnie; Zhang, Yiran; Wangia-Dixon, Ruth","year":2023,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 14(11), 1947-1958","doi":"10.1007/s13300-023-01473-7","pmid":"37740872","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06958","title":"Proteolysis of vaginally administered bovine lactoferrin: clearance, inter-subject variability, and implications for clinical dosing.","authors":"Hopp, Thomas P; Matthews, Maura-Ann H; Spiewak, Klaudyna; Athanasiou, Zafeiria; Blackmore, Richard S; Gelbfish, Gary A","year":2023,"journal":"Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine, 36(3), 531-547","doi":"10.1007/s10534-022-00481-7","pmid":"36580179","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06959","title":"Single dose intranasal oxytocin administration: Data from healthy younger and older adults.","authors":"Horta, Marilyn; Polk, Rebecca; Ebner, Natalie C","year":2023,"journal":"Data in brief, 51, 109669","doi":"10.1016/j.dib.2023.109669","pmid":"38020441","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06960","title":"Revealing the interaction between peptide drugs and permeation enhancers in the presence of intestinal bile salts.","authors":"Hossain, Shakhawath; Kneiszl, Rosita; Larsson, Per","year":2023,"journal":"Nanoscale, 15(47), 19180-19195","doi":"10.1039/d3nr05571j","pmid":"37982184","tags":["oral-bioavailability","drug-delivery"],"studyType":"computational","evidenceStrength":"moderate","keyFinding":"Two permeation enhancers — sodium caprate and SNAC (the technology behind oral semaglutide) — have opposite effects on different types of peptide drugs depending on the peptide's water solubility. In the presence of intestinal bile salts, both enhancers promoted the release of hydrophobic (fat-loving) peptides but inhibited the release of water-soluble peptides from molecular aggregates.\n\nSNAC caused insulin to form more beta-sheet structures, while sodium caprate preserved insulin's alpha-helical and random coil structures. These structural changes matter because they affect whether the peptide drug is active or aggregated when it reaches the intestinal wall. The findings suggest that permeation enhancer selection must be matched to each specific peptide's physical properties.","whyItMatters":"SNAC is the absorption enhancer that makes oral semaglutide (Rybelsus) possible — the first oral GLP-1 drug. Understanding exactly how SNAC and other enhancers interact with peptide drugs at the molecular level is critical for designing the next generation of oral peptide pills. This study reveals that the same enhancer can help or hinder absorption depending on the peptide's properties, which has major implications for oral formulation development.","specificNumbers":"2 permeation enhancers (SNAC + sodium caprate) · 4 peptides (octreotide, hexarelin, degarelix, insulin) · taurocholate bile salt · all-atom molecular dynamics simulations","methodology":"All-atom molecular dynamics simulations modeling interactions between two permeation enhancers (SNAC and sodium caprate), four peptide drugs (octreotide, hexarelin, degarelix, insulin), and intestinal bile salt (taurocholate). Supplemented with experimental FTIR spectroscopy to analyze insulin secondary structure changes in the presence of enhancers.","limitations":"Computational simulations model molecular interactions but may not fully capture the complexity of the intestinal environment, including mucus layers, epithelial cells, pH gradients, and enzymatic activity. The study tested four peptides, but the principles may not generalize to all peptide drugs. Experimental validation of the predicted release profiles in biological systems would strengthen the conclusions."},{"rthcId":"RPEP-06961","title":"Engineered peptide-drug conjugate provides sustained protection of retinal ganglion cells with topical administration in rats.","authors":"Hsueh, Henry T; Chou, Renee Ti; Rai, Usha; Kolodziejski, Patricia; Liyanage, Wathsala; Pejavar, Jahnavi; Mozzer, Ann; Davison, Charlotte; Appell, Matthew B; Kim, Yoo Chun; Leo, Kirby T; Kwon, HyeYoung; Sista, Maanasa; Anders, Nicole M; Hemingway, Avelina; Rompicharla, Sri Vishnu Kiran; Pitha, Ian; Zack, Donald J; Hanes, Justin; Cummings, Michael P; Ensign, Laura M","year":2023,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 362, 371-380","doi":"10.1016/j.jconrel.2023.08.058","pmid":"37657693","tags":["drug-delivery"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"A peptide-drug conjugate called HR97-SunitiGel, delivered as an eye drop in rats, provided up to two weeks of retinal ganglion cell protection after the last dose. This effectively doubled the therapeutic window compared to the drug formulation without the engineered peptide.\n\nThe system combined two technologies: a hypotonic gel-forming eye drop and a melanin-binding, cell-penetrating peptide. The peptide component extended how long the drug remained inside the eye, allowing once-daily dosing to achieve sustained therapeutic concentrations of sunitinib in the back of the eye.","whyItMatters":"Treating diseases at the back of the eye — like glaucoma and optic nerve damage — usually requires injections directly into the eye, which are painful and require clinic visits. Eye drops are far more convenient, but drugs from drops rarely reach the retina in useful amounts. This peptide-conjugate approach could make effective eye drop treatment for posterior eye diseases a reality, dramatically improving how patients manage chronic conditions.","specificNumbers":"Up to 2 weeks of neuroprotection after last dose · 2× therapeutic window vs. SunitiGel alone · Once daily topical dosing · Rat optic nerve injury model","methodology":"Researchers engineered a cell-penetrating and melanin-binding peptide (HR97) and conjugated it to sunitinib, then formulated it in a gel-forming eye drop system. They tested this in a rat model of optic nerve injury, measuring retinal ganglion cell survival and intraocular drug concentrations after once-daily topical dosing.","limitations":"This was an animal study in rats, which have much smaller eyes than humans — drug penetration dynamics differ significantly. The study used an optic nerve crush injury model, which may not fully replicate chronic human glaucoma. No human safety or efficacy data exist yet for this formulation."},{"rthcId":"RPEP-06962","title":"Corrected and republished from: \"VP4 Is a Determinant of Alpha-Defensin Modulation of Rotaviral Infection\".","authors":"Hu, Ciara T; Diaz, Karina; Yang, Linda C; Sharma, Anjali; Greenberg, Harry B; Smith, Jason G","year":2023,"journal":"Journal of virology, 97(10), e0096223","doi":"10.1128/jvi.00962-23","pmid":"37787534","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06963","title":"Gel-to-Solution Transition of Sulfhydryl Self-Assembled Peptide Hydrogels Undergoing Oxidative Modulation.","authors":"Hu, Mai; Liu, Zhengli; Shen, Zhiwei","year":2023,"journal":"ACS applied bio materials, 6(12), 5836-5841","doi":"10.1021/acsabm.3c00932","pmid":"38018082","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06964","title":"Cost-utility analysis of semaglutide for type 2 diabetes after its addition to the National Medical Insurance System in China.","authors":"Hu, Shanshan; Gu, Shengying; Qi, Chendong; Wang, Shuowen; Qian, Fengdan; Shi, Chenyang; Fan, Guorong","year":2023,"journal":"Diabetes, obesity & metabolism, 25(2), 387-397","doi":"10.1111/dom.14881","pmid":"36193880","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06965","title":"Comparison of exenatide alone or combined with metformin versus metformin in the treatment of polycystic ovaries: a systematic review and meta-analysis.","authors":"Hu, Yan; Song, Xiangxin; Hamiti, Shaila; Ma, Yanyong; Yusufu, Mainu; Wang, Xing; Zhang, Kaidi; Guo, Yanying","year":2023,"journal":"BMC endocrine disorders, 23(1), 250","doi":"10.1186/s12902-023-01497-x","pmid":"37974132","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06966","title":"Angiotensin-I-Converting Enzyme (ACE)-Inhibitory Peptides from the Collagens of Monkfish (Lophius litulon) Swim Bladders: Isolation, Characterization, Molecular Docking Analysis and Activity Evaluation.","authors":"Hu, Yu-Dong; Xi, Qing-Hao; Kong, Jing; Zhao, Yu-Qin; Chi, Chang-Feng; Wang, Bin","year":2023,"journal":"Marine drugs, 21(10)","doi":"10.3390/md21100516","pmid":"37888451","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06967","title":"Antimicrobial peptides in Dendrobium officinale: Genomic parameters, peptide structures, and gene expression patterns.","authors":"Huang, Huiming; Lee, Wen-Yee; Zou, Hui; Li, Haiming; Zhang, Shuhe; Li, Heping; Lin, Jiangbo","year":2023,"journal":"The plant genome, 16(3), e20348","doi":"10.1002/tpg2.20348","pmid":"37194434","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06968","title":"Effects of dulaglutide combined with insulin degludec on glucose fluctuations and appetite in type 2 diabetes.","authors":"Huang, Jinxin; Hua, Fei; Jiang, Xiaohong; Zhang, Xingguang; Yang, Minxing; Wang, Long; Huang, Xiaolin; Luo, Kaiming","year":2023,"journal":"Frontiers in endocrinology, 14, 1130470","doi":"10.3389/fendo.2023.1130470","pmid":"37255975","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Patients receiving dulaglutide plus insulin degludec had significantly lower glucose variability across all measures (SDBG, MAGE, LAGE, and PPGE) compared to insulin degludec alone (all p<0.05). The combination group achieved time-in-range (TIR) targets much faster: by day 10, 100% had TIR ≥70% compared to only 67% in the control group.\n\nAppetite decreased significantly at 1 week after starting dulaglutide but began to return by 3 months. At 6 months, 89.2% of patients in the combination group were still on dulaglutide, indicating strong persistence. TIR was significantly associated with preserved islet (beta cell) function.","whyItMatters":"Many type 2 diabetes patients on long-acting insulin still struggle with blood sugar spikes after meals and unpredictable fluctuations. This study shows that adding a GLP-1 agonist doesn't just lower average blood sugar — it specifically smooths out the dangerous peaks and valleys. The CGM data provides a granular, real-world view of how quickly the combination works, which is valuable information for both patients and clinicians deciding whether to add a GLP-1 drug to existing insulin therapy.","specificNumbers":"","methodology":"This was a retrospective study of 236 adults with type 2 diabetes. The experimental group received once-weekly dulaglutide combined with daily insulin degludec, while the control group received insulin degludec alone. Researchers tracked patients for up to 6 months, using continuous glucose monitoring (CGM) data to measure blood sugar fluctuations and time in range. Appetite was assessed using standardized scoring at multiple time points.","limitations":"This was a retrospective study, not a randomized controlled trial, so there may be selection bias in who received the combination therapy. The study did not report baseline characteristics in detail or adjust for confounders. Appetite was assessed by scoring rather than objective measures. The relatively short 6-month follow-up limits conclusions about long-term outcomes, and the study population may not be generalizable to all type 2 diabetes patients."},{"rthcId":"RPEP-06969","title":"An Efficient Peptidomics Screening for Exogenous Substrates and Inhibitory Peptides of the Dipeptidase ACE from Milk Hydrolysate.","authors":"Huang, Ju-Hsuan; Nong, Nhung Thi Phuong; Hsu, Jue-Liang","year":2023,"journal":"Pharmaceutics, 15(2)","doi":"10.3390/pharmaceutics15020425","pmid":"36839747","tags":[],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Using an integrated peptidomics screening approach, researchers identified 31 ACE substrates from 478 peptides found in milk hydrolysate. The study revealed specific rules governing which peptides ACE can cleave: the most common residue at the P1' cleavage position was leucine or serine, while ACE would not cleave peptides when P1' is proline, P2' is aspartate/glutamate, or P1 is isoleucine.\n\nTwo peptides — AYFYPELFR and HLPLPLLQSW — were identified as substrate-type ACE inhibitors that significantly slowed the breakdown of angiotensin I, the natural ACE substrate involved in blood pressure regulation. These milk-derived peptides could serve as natural ACE inhibitors.","whyItMatters":"ACE (angiotensin-converting enzyme) is the target of widely prescribed blood pressure drugs like lisinopril and enalapril. Identifying natural peptide inhibitors of ACE from food sources like milk could lead to functional foods or nutraceuticals with blood pressure-lowering properties. This study's peptidomics screening method also provides a systematic way to discover bioactive peptides from any food protein hydrolysate, accelerating the discovery of health-promoting peptides.","specificNumbers":"478 peptides identified · 31 ACE substrates confirmed · 2 substrate-type inhibitors: AYFYPELFR and HLPLPLLQSW · P1' preference: Leu/Ser · ACE blocked by Pro at P1', Asp/Glu at P2', Ile at P1","methodology":"The researchers integrated three techniques: ACE pre-incubation with milk hydrolysate peptides, liquid chromatography-mass spectrometry (LC-MS), and stable-isotope labeling. This allowed them to systematically identify which peptides in the complex mixture are ACE substrates. Activities were confirmed using synthetic peptides. The protective effects of identified substrates against ACE-mediated hydrolysis of angiotensin I were also tested.","limitations":"This is an in vitro biochemical study — the identified peptides have not been tested in living organisms. Whether these milk-derived peptides survive digestion, are absorbed intact, and reach ACE in the body at effective concentrations remains unknown. The two inhibitory peptides are relatively large (9–10 amino acids), which may limit their oral bioavailability."},{"rthcId":"RPEP-06970","title":"In vitro gastrointestinal digestion of highland barley protein: identification and characterization of novel bioactive peptides involved in gut cholecystokinin secretion.","authors":"Huang, Kai; Wang, Qingyu; Song, Hongdong; Cao, Hongwei; Guan, Xiao","year":2023,"journal":"Journal of the science of food and agriculture, 103(15), 7869-7876","doi":"10.1002/jsfa.12870","pmid":"37467368","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06971","title":"Rehmannia alcohol extract inhibits neuropeptide secretion and alleviates osteoarthritis pain through cartilage protection.","authors":"Huang, Yanfeng; Lin, Qing; Tan, Xue; Jia, Liangliang; Li, Hui; Zhu, Zaishi; Fu, Changlong; Wang, Lili; Liu, Linlong; Mao, Min; Yi, Zhouping; Ma, Dezun; Li, Xihai","year":2023,"journal":"Heliyon, 9(9), e19322","doi":"10.1016/j.heliyon.2023.e19322","pmid":"37674829","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Rehmannia alcohol extract and its active component Rehmannioside D delayed cartilage degradation and reduced inflammation in osteoarthritis rats. The extract significantly reduced secretion of calcitonin gene-related peptide (CGRP) and substance P (SP) — two neuropeptides central to pain signaling. Functional MRI revealed that the treatment reversed pathological changes in the cerebral cortex and hippocampus, indicating the extract influences brain pain processing regions in addition to its local anti-inflammatory effects at the joint.","whyItMatters":"Osteoarthritis pain affects hundreds of millions of people, and current treatments often have significant side effects with long-term use. Understanding that Rehmannia works by reducing pain neuropeptides like CGRP and substance P — the same targets as modern migraine drugs — could lead to new approaches for OA pain management. The dual mechanism of cartilage protection plus neuropeptide modulation is particularly interesting.","specificNumbers":"","methodology":"The study combined in vivo (rat osteoarthritis model) and in vitro experiments. Therapeutic effects were assessed through cartilage degradation markers, inflammatory markers, and measurement of CGRP and substance P secretion levels. Functional magnetic resonance imaging (fMRI) was used to evaluate changes in brain activity in pain-related regions. The active ingredient Rehmannioside D was also tested separately to identify the compound responsible for the effects.","limitations":"This is an animal study using rat osteoarthritis models, and the results may not directly translate to humans. The abstract does not provide specific quantitative data for the neuropeptide reductions or cartilage protection metrics. The dosing, duration, and route of administration in rats may not correspond to practical human dosing. As a herbal extract, standardization and quality control present additional challenges for clinical translation."},{"rthcId":"RPEP-06972","title":"Implications of Ozempic and Other Semaglutide Medications for Facial Plastic Surgeons.","authors":"Humphrey, Clinton D; Lawrence, Anna C","year":2023,"journal":"Facial plastic surgery : FPS, 39(6), 719-721","doi":"10.1055/a-2148-6321","pmid":"37541662","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06973","title":"Quantitative live-cell imaging of lipidated peptide transport through an epithelial cell layer.","authors":"Hundahl, Adam Coln; Weller, Arjen; Larsen, Jannik Bruun; Hjørringgaard, Claudia U; Hansen, Morten B; Mündler, Ann-Kathrin; Knuhtsen, Astrid; Kristensen, Kasper; Arnspang, Eva C; Andresen, Thomas Lars; Mortensen, Kim I; Marie, Rodolphe","year":2023,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 355, 122-134","doi":"10.1016/j.jconrel.2023.01.066","pmid":"36724849","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06974","title":"Discovery and Characterization of a Dual-Function Peptide Derived from Bitter Gourd Seed Protein Using Two Orthogonal Bioassay-Guided Fractionations Coupled with In Silico Analysis.","authors":"Hung, Wei-Ting; Sutopo, Christoper Caesar Yudho; Wu, Mei-Li; Hsu, Jue-Liang","year":2023,"journal":"Pharmaceuticals (Basel, Switzerland), 16(11)","doi":"10.3390/ph16111629","pmid":"38004494","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06975","title":"Patterns of anti-CGRP mAbs use and variation of triptan consumption following treatment initiation: A descriptive drug utilization study in the Tuscany region, Italy.","authors":"Hyeraci, Giulia; Paoletti, Olga; Iannone, Luigi Francesco; Gini, Rosa; De Cesaris, Francesco; Geppetti, Pierangelo; Roberto, Giuseppe","year":2023,"journal":"Headache, 63(10), 1391-1402","doi":"10.1111/head.14639","pmid":"37830925","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 624 new users of anti-CGRP mAbs (erenumab n=295, galcanezumab n=223, fremanezumab n=106), treatment persistence declined progressively: 69% at 6 months, 48% at 12 months, and only 6% at 15 months. Treatment switching between antibodies occurred in about 6% of patients at 15 months.\n\nFor patients with regular triptan use at baseline, mean monthly triptan consumption decreased by 4.4 dosage units at 3 months, 5.2 at 6 months, 5.5 at 9 months, 5.4 at 12 months, and 4.5 at 15 months. The patient population was predominantly female (78%) with a mean age of 49.2 years.","whyItMatters":"Clinical trials paint an optimistic picture of CGRP antibodies, but real-world use often tells a different story. The finding that half of patients discontinue within a year — despite these drugs being well-tolerated in trials — highlights the gap between trial settings and real clinical practice. At the same time, the consistent 5-dose reduction in monthly triptan use confirms these drugs do reduce migraine burden for those who stay on treatment.","specificNumbers":"","methodology":"This was a retrospective descriptive cohort study using the population-based administrative healthcare database of the Tuscany region, Italy. Patients with at least one anti-CGRP mAb dispensing between April 2019 and September 2021 were identified. Treatment persistence was analyzed using Kaplan-Meier curves over 15 months. Triptan consumption was measured as mean monthly dosage units in five consecutive 3-month windows and compared to the 6-month baseline period.","limitations":"Administrative database studies cannot capture clinical outcomes like migraine frequency, severity, or patient satisfaction — only medication dispensing patterns. The low 15-month persistence rate (6%) may partly reflect Italian prescribing regulations that require treatment reassessment rather than true discontinuation for lack of efficacy. The study did not assess reasons for discontinuation. Triptan dispensing is a proxy for acute migraine episodes but may not perfectly correlate with headache frequency."},{"rthcId":"RPEP-06976","title":"Neuronal and non-neuronal TRPA1 as therapeutic targets for pain and headache relief.","authors":"Iannone, Luigi F; Nassini, Romina; Patacchini, Riccardo; Geppetti, Pierangelo; De Logu, Francesco","year":2023,"journal":"Temperature (Austin, Tex.), 10(1), 50-66","doi":"10.1080/23328940.2022.2075218","pmid":"37187829","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06977","title":"Switching OnabotulinumtoxinA to Monoclonal Anti-CGRP Antibodies in Drug-Resistant Chronic Migraine.","authors":"Iannone, Luigi Francesco; Fattori, Davide; Marangoni, Martina; Benemei, Silvia; Chiarugi, Alberto; Geppetti, Pierangelo; De Cesaris, Francesco","year":2023,"journal":"CNS drugs, 37(2), 189-202","doi":"10.1007/s40263-022-00983-5","pmid":"36656298","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06978","title":"Predicting response to CGRP-monoclonal antibodies in patients with migraine in Japan: a single-centre retrospective observational study.","authors":"Ihara, Keiko; Ohtani, Seiya; Watanabe, Narumi; Takahashi, Nobuyuki; Miyazaki, Naoki; Ishizuchi, Kei; Hori, Satoko; Takemura, Ryo; Nakahara, Jin; Takizawa, Tsubasa","year":2023,"journal":"The journal of headache and pain, 24(1), 23","doi":"10.1186/s10194-023-01556-7","pmid":"36890436","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06979","title":"Effects of switching from liraglutide to semaglutide or dulaglutide in patients with type 2 diabetes: A randomized controlled trial.","authors":"Iijima, Takahiro; Shibuya, Makoto; Ito, Yuzuru; Terauchi, Yasuo","year":2023,"journal":"Journal of diabetes investigation, 14(6), 774-781","doi":"10.1111/jdi.14000","pmid":"36871272","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06980","title":"Cathelicidin LL-37 Activates Human Keratinocyte Autophagy through the P2X₇, Mechanistic Target of Rapamycin, and MAPK Pathways.","authors":"Ikutama, Risa; Peng, Ge; Tsukamoto, Saya; Umehara, Yoshie; Trujillo-Paez, Juan Valentin; Yue, Hainan; Nguyen, Hai Le Thanh; Takahashi, Miho; Kageyama, Shun; Komatsu, Masaaki; Okumura, Ko; Ogawa, Hideoki; Ikeda, Shigaku; Niyonsaba, François","year":2023,"journal":"The Journal of investigative dermatology, 143(5), 751-761.e7","doi":"10.1016/j.jid.2022.10.020","pmid":"36455652","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06981","title":"Short-Peptide Supramolecular Hydrogels for In Situ Growth of Metal-Organic Framework-Peptide Biocomposites.","authors":"Illescas-Lopez, Sara; Martin-Romera, Javier D; Mañas-Torres, Mari C; Lopez-Lopez, Modesto T; Cuerva, Juan M; Gavira, José A; Carmona, Francisco J; Álvarez de Cienfuegos, Luis","year":2023,"journal":"ACS applied materials & interfaces, 15(27), 32597-32609","doi":"10.1021/acsami.3c06943","pmid":"37390355","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06982","title":"Structure Characterization and Antihypertensive Effect of an Antioxidant Peptide Purified from Alcalase Hydrolysate of Velvet Antler.","authors":"Im, Seung Tae; Lee, Seung-Hong","year":2023,"journal":"Food science of animal resources, 43(1), 184-194","doi":"10.5851/kosfa.2022.e70","pmid":"36789190","tags":[],"studyType":"in vitro + animal study","evidenceStrength":"low","keyFinding":"Researchers isolated a specific five-amino-acid peptide (Asp-Asn-Arg-Tyr-Tyr, molecular weight 730.31 Da) from enzymatic digestion of velvet antler that powerfully inhibits angiotensin I-converting enzyme (ACE), a key enzyme in blood pressure regulation. The peptide showed an IC50 value of 3.72 μM against ACE — indicating potent inhibitory activity at very low concentrations. Molecular docking analysis confirmed stable binding between the peptide and ACE at multiple active-site residues. When given orally to spontaneously hypertensive rats, the peptide significantly reduced blood pressure.","whyItMatters":"ACE inhibitors are among the most widely prescribed blood pressure medications, but current drugs are synthetic pharmaceuticals with side effects like chronic cough. Food-derived peptides that naturally inhibit ACE represent a potential alternative — functional food ingredients that could help manage blood pressure with fewer side effects. Identifying the exact structure and mechanism of these peptides, as this study does, is a critical step toward developing them as practical nutraceuticals.","specificNumbers":"Pentapeptide MW 730.31 Da · IC50 = 3.72 μM against ACE · Sequence: Asp-Asn-Arg-Tyr-Tyr","methodology":"The peptide was purified from alcalase hydrolysate of velvet antler (deer antler in its growth stage). Its structure was determined by quadrupole time-of-flight electrospray ionization mass spectroscopy. ACE inhibition was measured using enzyme reaction assays. In silico molecular docking analysis modeled how the peptide binds to ACE. The antihypertensive effect was tested in vivo by oral administration to spontaneously hypertensive rats (SHRs), a standard animal model for hypertension research.","limitations":"This study was conducted in vitro and in an animal model — no human data exists for this peptide. The spontaneously hypertensive rat is a useful but imperfect model for human hypertension. The study doesn't address whether the peptide survives gastrointestinal digestion intact in humans, what the optimal dose would be, or whether the blood pressure effects are sustained with chronic use. Velvet antler sourcing also raises sustainability and ethical considerations."},{"rthcId":"RPEP-06983","title":"Irinotecan-induced gastrointestinal damage alters the expression of peptide transporter 1 and absorption of cephalexin in rats.","authors":"Imaoka, Ayuko; Hattori, Tomoki; Akiyoshi, Takeshi; Ohtani, Hisakazu","year":2023,"journal":"Biopharmaceutics & drug disposition, 44(5), 372-379","doi":"10.1002/bdd.2372","pmid":"37507848","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06984","title":"Evaluation of the biocontrol potential of a collagen peptide/trehalose-based Cronobacter sakazakii phage powder in rehydrated powdered infant formula.","authors":"Imm, Seulgi; Chang, Yoonjee","year":2023,"journal":"Food research international (Ottawa, Ont.), 173(Pt 1), 113257","doi":"10.1016/j.foodres.2023.113257","pmid":"37803569","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06985","title":"Enhanced Contraction of Arterial Smooth Muscle Cell in Skin Artery Is Sensitive to Hyperpolarization Mediated by BKCa Channel in Chronic Constriction Injury Model Rat.","authors":"Ishida, Hirotake; Ishikawa, Tomohisa; Saito, Shin-Ya","year":2023,"journal":"Biological & pharmaceutical bulletin, 46(3), 399-403","doi":"10.1248/bpb.b22-00603","pmid":"36858567","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06986","title":"A phase 1 trial of NY-ESO-1-specific TCR-engineered T-cell therapy combined with a lymph node-targeting nanoparticulate peptide vaccine for the treatment of advanced soft tissue sarcoma.","authors":"Ishihara, Mikiya; Nishida, Yoshihiro; Kitano, Shigehisa; Kawai, Akira; Muraoka, Daisuke; Momose, Fumiyasu; Harada, Naozumi; Miyahara, Yoshihiro; Seo, Naohiro; Hattori, Hiroyoshi; Takada, Kohichi; Emori, Makoto; Kakunaga, Shigeki; Endo, Makoto; Matsumoto, Yoshihiro; Sasada, Tetsuro; Sato, Eiichi; Yamada, Tomomi; Matsumine, Akihiko; Nagata, Yasuhiro; Watanabe, Takashi; Kageyama, Shinichi; Shiku, Hiroshi","year":2023,"journal":"International journal of cancer, 152(12), 2554-2566","doi":"10.1002/ijc.34453","pmid":"36727538","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06987","title":"Treatment Satisfaction and Quality of Life with Tirzepatide Versus Dulaglutide Among Japanese Patients with Type 2 Diabetes: Exploratory Evaluation of the SURPASS J-mono Trial.","authors":"Ishii, Hitoshi; Oura, Tomonori; Takeuchi, Masakazu","year":2023,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 14(12), 2173-2183","doi":"10.1007/s13300-023-01485-3","pmid":"37843771","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06988","title":"One-Pot Approach to Synthesize Tough and Cell Adhesive Double-Network Hydrogels Consisting of Fully Synthetic Materials of Self-Assembling Peptide and Poly(ethylene glycol).","authors":"Ishikawa, Shohei; Sakai, Takamasa","year":2023,"journal":"ACS applied bio materials, 6(12), 5282-5289","doi":"10.1021/acsabm.3c00562","pmid":"37862142","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In situ mixing of RADA16 self-assembling peptide with poly(ethylene glycol) produced double-network hydrogels through sequential network formation: first RADA16 self-assembly, then PEG chemical cross-linking. The resulting hydrogels exhibited up to a 10-fold increase in fracture energy compared to single-network controls, demonstrating dramatically improved mechanical toughness.\n\nCells seeded on the DN hydrogel surfaces showed good attachment, confirming the cell-adhesive properties of the RADA16 peptide component were preserved. The entire process used only synthetic, biocompatible materials and avoided free-radical polymerization — a key advantage for biological applications.","whyItMatters":"Tissue engineering requires scaffolds that are both mechanically robust and biologically compatible — a combination that has been difficult to achieve simply and safely. This one-pot method using fully synthetic, biocompatible materials eliminates the toxic free-radical polymerization steps that limit current approaches. The 10-fold toughness improvement opens possibilities for load-bearing tissue engineering applications like cartilage and bone repair.","specificNumbers":"","methodology":"RADA16 peptide and PEG were mixed in a one-pot approach at conditions that allowed sequential network formation. The resulting double-network hydrogels were characterized mechanically (fracture energy measurements) and biologically (cell seeding and attachment assays). The study compared single-network and double-network hydrogel properties to quantify the DN effect.","limitations":"This is a materials characterization study with only preliminary cell attachment data — no functional tissue engineering or in vivo testing was performed. The range of cell types and tissues this hydrogel could support is unknown. Long-term stability, degradation kinetics, and in vivo biocompatibility were not assessed. Only one peptide (RADA16) and one polymer (PEG) combination was tested. The mechanical properties, while significantly improved, may still not match native load-bearing tissues."},{"rthcId":"RPEP-06989","title":"A new triphenylphosphonium-conjugated amphipathic cationic peptide with improved cell-penetrating and ROS-targeting properties.","authors":"Ishkaeva, Rezeda A; Salakhieva, Diana V; Garifullin, Ruslan; Alshadidi, Raghad; Laikov, Alexander V; Yergeshov, Abdulla A; Kamalov, Marat I; Abdullin, Timur I","year":2023,"journal":"Current research in pharmacology and drug discovery, 4, 100148","doi":"10.1016/j.crphar.2022.100148","pmid":"36593927","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06990","title":"Bioactive molecules from terrestrial and seafood resources in hypertension treatment: focus on molecular mechanisms and targeted therapies.","authors":"Islam, Md Rezaul; Dhar, Puja Sutro; Akash, Shopnil; Syed, Sabeena Hussain; Gupta, Jeetendra Kumar; Gandla, Kumaraswamy; Akter, Muniya; Rauf, Abdur; Hemeg, Hassan A; Anwar, Yasir; Aljohny, Bassam Oudh; Wilairatana, Polrat","year":2023,"journal":"Natural products and bioprospecting, 13(1), 45","doi":"10.1007/s13659-023-00411-1","pmid":"37902881","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06991","title":"Substance P and Neurokinin-1 Receptor System in Thyroid Cancer: Potential Targets for New Molecular Therapies.","authors":"Isorna, Inmaculada; González-Moles, Miguel Ángel; Muñoz, Miguel; Esteban, Francisco","year":2023,"journal":"Journal of clinical medicine, 12(19)","doi":"10.3390/jcm12196409","pmid":"37835053","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06992","title":"Effect of dulaglutide and long-acting insulin combination therapy in patients with type 2 diabetes: a retrospective observational study.","authors":"Ito, Kohei; Satoh, Shinobu; Kondo, Yoshinobu; Tamura, Haruka; Hasebe, Masanori; Terauchi, Yasuo","year":2023,"journal":"Diabetology international, 14(1), 51-57","doi":"10.1007/s13340-022-00592-z","pmid":"36636162","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06993","title":"Early Effect of Calcitonin Gene-related Peptide Monoclonal Antibodies in Migraine with Medication Overuse: A Single-center Retrospective Study.","authors":"Ito, Yasuo; Mitsufuji, Takashi; Okada, Mariko; Fujita, Shugo; Yokoyama, Ryu; Kawasaki, Hitoshi; Yamamoto, Toshimasa","year":2023,"journal":"Internal medicine (Tokyo, Japan), 62(23), 3455-3460","doi":"10.2169/internalmedicine.1471-22","pmid":"37062749","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06994","title":"Curcumin-loaded porous particles functionalized with pH-responsive cell-penetrating peptide for colorectal cancer targeted drug delivery.","authors":"Izadi, Zhila; Rashidi, Maryam; Derakhshankhah, Hossein; Dolati, Mozhdeh; Ghanbari Kermanshahi, Mohammad; Adibi, Hadi; Samadian, Hadi","year":2023,"journal":"RSC advances, 13(49), 34587-34597","doi":"10.1039/d3ra06270h","pmid":"38024994","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06995","title":"The SP/NK1R system promotes the proliferation of breast cancer cells through NF-κB-mediated inflammatory responses.","authors":"Jafarinezhad, Samine; Assaran Darban, Reza; Javid, Hossein; Hashemy, Seyed Isaac","year":2023,"journal":"Cell biochemistry and biophysics, 81(4), 787-794","doi":"10.1007/s12013-023-01171-y","pmid":"37740877","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06996","title":"Treatment with the dual-incretin agonist DA-CH5 demonstrates potent therapeutic effect in a rat model of Wolfram Syndrome.","authors":"Jagomäe, Toomas; Gaur, Nayana; Seppa, Kadri; Reimets, Riin; Pastak, Marko; Plaas, Mihkel; Kaasik, Allen; Vasar, Eero; Plaas, Mario","year":2023,"journal":"Frontiers in endocrinology, 14, 1234925","doi":"10.3389/fendo.2023.1234925","pmid":"37900147","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06997","title":"Impact of Peptide Sequence on Functional siRNA Delivery and Gene Knockdown with Cyclic Amphipathic Peptide Delivery Agents.","authors":"Jagrosse, Melissa L; Baliga, Uday K; Jones, Christopher W; Russell, Jade J; García, Claudia I; Najar, Rauf Ahmad; Rahman, Arshad; Dean, David A; Nilsson, Bradley L","year":2023,"journal":"Molecular pharmaceutics, 20(12), 6090-6103","doi":"10.1021/acs.molpharmaceut.3c00455","pmid":"37963105","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06998","title":"Lactoferrin-derived chimeric peptide (LFch) strongly boosts TGFβ1-mediated inducible Treg differentiation possibly through downregulating TCR/CD28 signalling.","authors":"Jang, Young-Saeng; Yang, Seok-Won; Kim, Tae-Gyu; Song, Ha-Eon; Park, Sunhee; Lee, Eun Hye; Kang, Seung-Goo; Yoon, Sung-Il; Ko, Hyun-Jeong; Lee, Geun-Shik; Park, Seok-Rae; Seo, Su Ryeon; Kim, Pyeung-Hyeun","year":2023,"journal":"Immunology, 168(1), 110-119","doi":"10.1111/imm.13566","pmid":"36054548","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-06999","title":"The evolution of colistin resistance increases bacterial resistance to host antimicrobial peptides and virulence.","authors":"Jangir, Pramod K; Ogunlana, Lois; Szili, Petra; Czikkely, Marton; Shaw, Liam P; Stevens, Emily J; Yu, Yang; Yang, Qiue; Wang, Yang; Pál, Csaba; Walsh, Timothy R; MacLean, Craig R","year":2023,"journal":"eLife, 12","doi":"10.7554/eLife.84395","pmid":"37094804","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07000","title":"Cerebrolysin in Patients with TBI: Systematic Review and Meta-Analysis.","authors":"Jarosz, Konrad; Kojder, Klaudyna; Andrzejewska, Agata; Solek-Pastuszka, Joanna; Jurczak, Anna","year":2023,"journal":"Brain sciences, 13(3)","doi":"10.3390/brainsci13030507","pmid":"36979317","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07001","title":"New Frontiers in Obesity Treatment: GLP-1 and Nascent Nutrient-Stimulated Hormone-Based Therapeutics.","authors":"Jastreboff, Ania M; Kushner, Robert F","year":2023,"journal":"Annual review of medicine, 74, 125-139","doi":"10.1146/annurev-med-043021-014919","pmid":"36706749","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07002","title":"Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial.","authors":"Jastreboff, Ania M; Kaplan, Lee M; Frías, Juan P; Wu, Qiwei; Du, Yu; Gurbuz, Sirel; Coskun, Tamer; Haupt, Axel; Milicevic, Zvonko; Hartman, Mark L","year":2023,"journal":"The New England journal of medicine, 389(6), 514-526","doi":"10.1056/NEJMoa2301972","pmid":"37366315","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07003","title":"Stitched peptides as potential cell permeable inhibitors of oncogenic DAXX protein.","authors":"Jelinska, Clare; Kannan, Srinivasaraghavan; Frosi, Yuri; Ramlan, Siti Radhiah; Winnerdy, Fernaldo; Lakshminarayanan, Rajamani; Johannes, Charles W; Brown, Christopher J; Phan, Anh-Tuan; Rhodes, Daniela; Verma, Chandra S","year":2023,"journal":"RSC chemical biology, 4(12), 1096-1110","doi":"10.1039/d3cb00149k","pmid":"38033728","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Novel stapled/stitched peptides were designed to target the N-terminal helical bundle of the DAXX oncoprotein, binding with higher affinity than DAXX's known natural interaction partners (Rassf1C, p53, Mdm2, ATRX). The peptides effectively inhibited DAXX and released its auto-inhibited SUMO interaction motif, enabling it to bind SUMO-1. Critically, the stitched peptides entered cells and maintained nanomolar intracellular concentrations for at least 24 hours without disrupting cell membranes.","whyItMatters":"DAXX is upregulated in many common cancers and its suppression reduces tumor progression, but it has been considered difficult to drug because its critical interactions occur inside cells. These stitched peptides are the first reported cell-permeable inhibitors targeting DAXX, demonstrating that this oncoprotein is druggable and opening a new avenue for cancer therapy development.","specificNumbers":"","methodology":"Using structural information about the DAXX N-terminal helical bundle domain, the researchers designed stapled and stitched peptide variants targeting the surface where multiple protein partners bind. Binding affinity was measured and compared to known DAXX interaction partners. The effect on DAXX's auto-inhibited SUMO interaction motif was assessed. Cell permeability was evaluated by measuring intracellular peptide concentrations over 24 hours, and membrane integrity was confirmed to rule out non-specific membrane disruption.","limitations":"This is an early-stage drug development study focused on in vitro characterization — no in vivo animal models or efficacy data were included. While the peptides enter cells at nanomolar levels, their ability to suppress DAXX-dependent tumor growth in living organisms has not been demonstrated. The therapeutic window between DAXX inhibition and normal cellular function is not yet characterized. Specific cancer cell line data and dose-response relationships are not reported in the abstract."},{"rthcId":"RPEP-07004","title":"Efficacy of the Glucagon-Like Peptide-1 Receptor Agonists Liraglutide and Semaglutide for the Treatment of Weight Regain After Bariatric surgery: a Retrospective Observational Study.","authors":"Jensen, Anders Boisen; Renström, Frida; Aczél, Stefan; Folie, Patrick; Biraima-Steinemann, Magdalena; Beuschlein, Felix; Bilz, Stefan","year":2023,"journal":"Obesity surgery, 33(4), 1017-1025","doi":"10.1007/s11695-023-06484-8","pmid":"36765019","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07005","title":"Approved Anti-Obesity Medications in 2022 KSSO Guidelines and the Promise of Phase 3 Clinical Trials: Anti-Obesity Drugs in the Sky and on the Horizon.","authors":"Jeon, Eonju; Lee, Ki Young; Kim, Kyoung-Kon","year":2023,"journal":"Journal of obesity & metabolic syndrome, 32(2), 106-120","doi":"10.7570/jomes23032","pmid":"37349257","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies the current approved anti-obesity medications and their successors:\n\n**Currently approved (long-term):** Orlistat, naltrexone/bupropion, phentermine/topiramate, liraglutide (GLP-1 RA), semaglutide (GLP-1 RA)\n\n**Awaiting approval:** Tirzepatide (dual GLP-1/GIP agonist)\n\n**In Phase 3 trials:** Semaglutide/cagrilintide combination (GLP-1 + amylin analog), oral semaglutide for obesity, orforglipron (oral non-peptide GLP-1 agonist), BI 456906, retartrutide (triple GLP-1/GIP/glucagon agonist)\n\nThe Korean KSSO guidelines recommend pharmacotherapy for adults with BMI ≥25 kg/m² who haven't responded to non-pharmacological treatments, emphasizing personalized drug selection based on individual patient characteristics.","whyItMatters":"The obesity drug landscape is undergoing its most rapid transformation in history. This review provides a comprehensive snapshot of where we stand — from established drugs to next-generation peptide-based therapies that may produce weight loss approaching what bariatric surgery achieves. Understanding this pipeline is essential for clinicians making treatment decisions and for patients navigating their options.","specificNumbers":"","methodology":"This is a narrative review of approved anti-obesity medications and drugs in Phase 3 clinical trials, structured around the 2022 Korean Society for the Study of Obesity (KSSO) clinical guidelines. The authors review evidence from major clinical trials for each drug and discuss the evolving treatment landscape.","limitations":"The review focuses primarily on the Korean context (KSSO guidelines with BMI ≥25 threshold), which may not directly apply to other populations where different BMI thresholds are used. As a 2023 publication, some of the pipeline drugs discussed have since had trial results released or regulatory decisions made. Long-term safety data is limited for newer agents, and cost/access issues are acknowledged but not deeply addressed."},{"rthcId":"RPEP-07006","title":"Melittin derived peptide-drug conjugate, M-DM1, inhibits tumor progression and induces effector cell infiltration in melanoma by targeting M2 tumor-associated macrophages.","authors":"Jeong, Chanmi; Kim, Jeongdong; Han, Ik-Hwan; Kim, Soyoung; Choi, Ilseob; Kim, Hongsung; Jeong, Jin-Hyun; Bae, Hyunsu","year":2023,"journal":"Frontiers in immunology, 14, 1178776","doi":"10.3389/fimmu.2023.1178776","pmid":"37122692","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07007","title":"Effects of Specific Bioactive Collagen Peptides in Combination with Concurrent Training on Running Performance and Indicators of Endurance Capacity in Men: A Randomized Controlled Trial.","authors":"Jerger, Simon; Jendricke, Patrick; Centner, Christoph; Bischof, Kevin; Kohl, Jan; Keller, Simon; Gollhofer, Albert; König, Daniel","year":2023,"journal":"Sports medicine - open, 9(1), 103","doi":"10.1186/s40798-023-00654-9","pmid":"37935999","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07008","title":"Specific collagen peptides increase adaptions of patellar tendon morphology following 14-weeks of high-load resistance training: A randomized-controlled trial.","authors":"Jerger, Simon; Centner, Christoph; Lauber, Benedikt; Seynnes, Olivier; Friedrich, Till; Lolli, David; Gollhofer, Albert; König, Daniel","year":2023,"journal":"European journal of sport science, 23(12), 2329-2339","doi":"10.1080/17461391.2023.2232758","pmid":"37424319","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In a 14-week randomized, placebo-controlled trial, 50 healthy men who took 5g of specific collagen peptides daily alongside resistance training showed significantly greater improvements in patellar tendon structural properties compared to placebo. The study also assessed tendon stiffness, maximal voluntary knee extension strength, and rectus femoris muscle cross-sectional area. The collagen peptide supplementation led to significantly greater patellar tendon morphological adaptations beyond what resistance training alone achieved.","whyItMatters":"Tendons adapt to training much more slowly than muscles, creating an imbalance that increases injury risk during strength training programs. If collagen peptides can accelerate tendon adaptation, they could help athletes and patients undergoing rehabilitation strengthen their tendons alongside their muscles — potentially reducing overuse injury risk and improving training outcomes.","specificNumbers":"","methodology":"Randomized, placebo-controlled trial registered in the German Clinical Trials Register (DRKS00029244). Fifty healthy, moderately active male participants completed a 14-week resistance training program with three weekly sessions at 70-85% of 1 repetition maximum for the knee extensors. The supplementation group received 5g of specific collagen peptides daily; the control group received an identical-looking placebo. Outcome measures included patellar tendon structural properties (morphology), tendon stiffness, maximal voluntary knee extension strength, and rectus femoris cross-sectional area.","limitations":"The abstract text appears truncated, preventing full assessment of specific outcome values and statistical significance levels. The study included only healthy, moderately active males, limiting generalizability to women, older adults, and clinical populations. The 14-week duration may not capture long-term tendon remodeling. The multi-component supplement intervention (specific collagen peptides) doesn't identify which peptide fractions drive the effect."},{"rthcId":"RPEP-07009","title":"Animal studies reveal that the ghrelin pathway regulates alcohol-mediated responses.","authors":"Jerlhag, Elisabet","year":2023,"journal":"Frontiers in psychiatry, 14, 1050973","doi":"10.3389/fpsyt.2023.1050973","pmid":"36970276","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07010","title":"Development of a peptide drug restoring AMPK and adipose tissue functionality in cancer cachexia.","authors":"Ji, Honglei; Englmaier, Felix; Morigny, Pauline; Giroud, Maude; Gräsle, Pamina; Brings, Sebastian; Szendrödi, Julia; Berriel Diaz, Mauricio; Plettenburg, Oliver; Herzig, Stephan; Rohm, Maria","year":2023,"journal":"Molecular therapy : the journal of the American Society of Gene Therapy, 31(8), 2408-2421","doi":"10.1016/j.ymthe.2023.06.020","pmid":"37408309","tags":["cell-penetrating-peptide","ampk","cachexia"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"Researchers developed a novel peptide called Pen-X-ACIP that stabilizes the AMPK enzyme complex in fat tissue — a process that breaks down during cancer cachexia. When injected into tumor-bearing mice, the peptide prevented cachexia progression, preserved body weight and fat tissue mass, and did not affect tumor growth or cause side effects in other organs. The peptide was efficiently taken up by fat cells, inhibited the excessive fat breakdown (lipolysis) that drives wasting, and restored AMPK signaling. It also worked in human fat cells in the lab, providing a proof of concept for a first-in-class therapy.","whyItMatters":"Cancer cachexia — the severe muscle and fat wasting that affects up to 80% of advanced cancer patients — has no approved treatment. This study identifies a specific molecular target (AMPK destabilization in fat tissue) and delivers a peptide drug that addresses it. By using a cell-penetrating peptide to get the drug inside fat cells, the researchers created a potentially targeted approach that doesn't interfere with cancer treatment.","specificNumbers":"Pen-X-ACIP prevented cachexia progression · Preserved body weight and adipose tissue mass · No side effects in peripheral organs · No effect on tumor growth · Effective in human adipocytes in vitro","methodology":"The team designed a peptide (ACIP) that stabilizes the AMPK complex, fused it to the cell-penetrating peptide penetratin via a chemical linker, and tested it in cell cultures and tumor-bearing mice. They measured fat cell uptake, lipolysis inhibition, AMPK signaling restoration, tissue distribution after injection, body weight, fat mass, and tumor growth. They also tested the peptide's activity in human fat cells.","limitations":"This is preclinical proof-of-concept work in mice — no human trials have been conducted. The abstract does not report specific quantitative results (exact weight preservation numbers, sample sizes). Long-term safety and efficacy data are not available. The peptide requires injection (intraperitoneal), and it's unknown if other delivery routes would work. Whether results in mouse cachexia models translate to the complex presentation of human cancer cachexia remains to be determined."},{"rthcId":"RPEP-07011","title":"A phase 2 randomised controlled trial of mazdutide in Chinese overweight adults or adults with obesity.","authors":"Ji, Linong; Jiang, Hongwei; Cheng, Zhifeng; Qiu, Wei; Liao, Lin; Zhang, Yawei; Li, Xiaoli; Pang, Shuguang; Zhang, Lihui; Chen, Liming; Yang, Tao; Li, Yan; Qu, Shen; Wen, Jie; Gu, Jieyu; Deng, Huan; Wang, Yanqi; Li, Li; Han-Zhang, Han; Ma, Qingyang; Qian, Lei","year":2023,"journal":"Nature communications, 14(1), 8289","doi":"10.1038/s41467-023-44067-4","pmid":"38092790","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07012","title":"Goat milk-derived short chain peptides: Peptide LPYV as species-specific characteristic and their versatility bioactivities by MOF@Fe3O4@GO mesoporous magnetic-based peptidomics.","authors":"Jia, Wei; Du, An; Fan, Zibian; Shi, Lin","year":2023,"journal":"Food research international (Ottawa, Ont.), 164, 112442","doi":"10.1016/j.foodres.2022.112442","pmid":"36738007","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07013","title":"Self-cyclisation as a general and efficient platform for peptide and protein macrocyclisation.","authors":"Jia, Xinying; Chin, Yanni K-Y; Zhang, Alan H; Crawford, Theo; Zhu, Yifei; Fletcher, Nicholas L; Zhou, Zihan; Hamilton, Brett R; Stroet, Martin; Thurecht, Kristofer J; Mobli, Mehdi","year":2023,"journal":"Communications chemistry, 6(1), 48","doi":"10.1038/s42004-023-00841-5","pmid":"36871076","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The researchers engineered a self-cyclising 'autocyclase' protein that performs a unimolecular (single-molecule) head-to-tail macrocyclisation reaction. This approach is fundamentally different from existing enzyme-catalysed methods because it is a controllable self-reaction rather than requiring a separate enzyme to act on the substrate. The autocyclase produced cyclic peptides and proteins in high yield, and the unimolecular reaction mechanism addresses existing challenges in enzymatic cyclisation, such as substrate competition and concentration-dependent efficiency.","whyItMatters":"Cyclic peptides are among the most promising drug candidates in modern pharmaceutical development because their ring structure makes them resistant to degradation and improves their ability to bind targets. However, making cyclic peptides efficiently has been a major bottleneck. This autocyclase platform provides a simpler, more controllable method that could accelerate the production of cyclic peptide drugs and research tools.","specificNumbers":"","methodology":"The team used protein engineering to design an autocyclase — a protein containing a built-in self-cyclisation domain. They characterised the reaction mechanism and optimised conditions for controllable cyclisation. The method was validated by producing several known cyclic peptides and proteins, including cyclised nanodiscs (cNDs) used for studying membrane receptors.","limitations":"The abstract does not provide specific yield percentages or direct comparisons to existing cyclisation methods, making it difficult to quantitatively assess the advantage over current approaches. The range of peptide/protein sizes and sequences compatible with the autocyclase system is not fully characterised from the abstract alone. Scale-up feasibility for industrial production is also not addressed."},{"rthcId":"RPEP-07014","title":"The Modified Exenatide Microspheres: PLGA-PEG-PLGA Gel and Zinc-Exenatide Complex Synergistically Reduce Burst Release and Shorten Platform Stage.","authors":"Jiang, Wenjing; Gao, Xiangjun; Wang, Qiuli; Chen, Yang; Li, Dan; Zhang, Xiaoyan; Yang, Xinggang","year":2023,"journal":"AAPS PharmSciTech, 24(8), 251","doi":"10.1208/s12249-023-02705-6","pmid":"38036924","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07015","title":"Integration of metabolomics and peptidomics reveals distinct molecular landscape of human diabetic kidney disease.","authors":"Jiang, Xinrong; Liu, Xingyue; Qu, Xuetong; Zhu, Pingya; Wo, Fangjie; Xu, Xinran; Jin, Juan; He, Qiang; Wu, Jianmin","year":2023,"journal":"Theranostics, 13(10), 3188-3203","doi":"10.7150/thno.80435","pmid":"37351171","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07016","title":"Neuropeptides Modulate Feeding via the Dopamine Reward Pathway.","authors":"Jin, Ruijie; Sun, Shanbin; Hu, Yang; Zhang, Hongfei; Sun, Xiangrong","year":2023,"journal":"Neurochemical research, 48(9), 2622-2643","doi":"10.1007/s11064-023-03954-4","pmid":"37233918","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07017","title":"Pharmaceutical aspects of novel CGRP inhibitors used in the prophylaxis and treatment of migraine.","authors":"Jinesh, Sandhya","year":2023,"journal":"Inflammopharmacology, 31(5), 2245-2251","doi":"10.1007/s10787-023-01276-z","pmid":"37421480","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07018","title":"Development of an antibody fused with an antimicrobial peptide targeting Pseudomonas aeruginosa: A new approach to prevent and treat bacterial infections.","authors":"Johnson, Kenneth; Delaney, James C; Guillard, Thomas; Reffuveille, Fany; Varin-Simon, Jennifer; Li, Kai; Wollacott, Andrew; Frapy, Eric; Mong, Surin; Tissire, Hamid; Viswanathan, Karthik; Touti, Faycal; Babcock, Gregory J; Shriver, Zachary; Pentelute, Bradley L; Plante, Obadiah; Skurnik, David","year":2023,"journal":"PLoS pathogens, 19(9), e1011612","doi":"10.1371/journal.ppat.1011612","pmid":"37676873","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The antibody-drug conjugate (ADC) was created by fusing an antimicrobial peptide to the C-terminal end of the monoclonal antibody VSX, which targets P. aeruginosa lipopolysaccharide core. The ADC rapidly killed Pseudomonas strains, showed minimal toxicity to mammalian cells, and protected mice from P. aeruginosa lung infection when administered therapeutically. Additionally, the ADC was synergistic with several classes of conventional antibiotics, suggesting it could enhance existing treatments rather than replace them.","whyItMatters":"Pseudomonas aeruginosa is one of the most dangerous drug-resistant bacteria worldwide, causing serious lung infections particularly in immunocompromised patients and those with cystic fibrosis. Unlike broad-spectrum antibiotics that kill beneficial bacteria and promote resistance, this targeted approach kills only Pseudomonas, preserving the microbiome. The synergy with existing antibiotics means it could revitalize drugs that are losing effectiveness against resistant strains.","specificNumbers":"","methodology":"Researchers designed the ADC by genetically fusing an antimicrobial peptide to the VH and/or VL chains of the anti-Pseudomonas monoclonal antibody VSX. The conjugate was characterized in vitro for bactericidal activity against P. aeruginosa strains, cytotoxicity against mammalian cells, and synergy with antibiotics. Therapeutic efficacy was tested in a mouse model of P. aeruginosa lung infection.","limitations":"The study is preclinical, tested only in mice. The conjugate targets Pseudomonas aeruginosa specifically and would not work against other pathogens without redesign. Manufacturing antibody-peptide conjugates at scale is complex and costly compared to traditional antibiotics. Long-term safety and the potential for bacteria to develop resistance to the conjugate have not been assessed. The mouse lung infection model may not fully represent human Pseudomonas infections."},{"rthcId":"RPEP-07019","title":"Substance P Exacerbates the Inflammatory and Pro-osteoclastogenic Responses of Murine Osteoclasts and Osteoblasts to Staphylococcus aureus.","authors":"Johnson, M Brittany; Suptela, Samantha R; Sipprell, Sophie E; Marriott, Ian","year":2023,"journal":"Inflammation, 46(1), 256-269","doi":"10.1007/s10753-022-01731-z","pmid":"36040535","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07020","title":"Glucose metabolism, gut-brain hormones, and acromegaly treatment: an explorative single centre descriptive analysis.","authors":"Jørgensen, Nanna Thurmann; Erichsen, Trine Møller; Jørgensen, Morten Buus; Idorn, Thomas; Feldt-Rasmussen, Bo; Holst, Jens J; Feldt-Rasmussen, Ulla; Klose, Marianne","year":2023,"journal":"Pituitary, 26(1), 152-163","doi":"10.1007/s11102-022-01297-x","pmid":"36609655","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07021","title":"Synthesis of Short Peptides with Perfluoroalkyl Side Chains and Evaluation of Their Cellular Uptake Efficiency.","authors":"Kadota, Koji; Mikami, Toshiki; Kohata, Ai; Morimoto, Jumpei; Sando, Shinsuke; Aikawa, Kohsuke; Okazoe, Takashi","year":2023,"journal":"Chembiochem : a European journal of chemical biology, 24(21), e202300374","doi":"10.1002/cbic.202300374","pmid":"37430341","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07022","title":"A heptadeca amino acid peptide subunit of cathelicidin LL-37 has previously unreported antifungal activity.","authors":"Kalimuthu, Shanthini; Pudipeddi, Akhila; Braś, Grażyna; Tanner, Julian A; Rapala-Kozik, Maria; Leung, Yiu Yan; Neelakantan, Prasanna","year":2023,"journal":"APMIS : acta pathologica, microbiologica, et immunologica Scandinavica, 131(11), 584-600","doi":"10.1111/apm.13322","pmid":"37150907","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07023","title":"Stomach perforation-induced general occlusion/occlusion-like syndrome and stable gastric pentadecapeptide BPC 157 therapy effect.","authors":"Kalogjera, Luka; Krezic, Ivan; Smoday, Ivan Maria; Vranes, Hrvoje; Zizek, Helena; Yago, Haidi; Oroz, Katarina; Vukovic, Vlasta; Kavelj, Ivana; Novosel, Luka; Zubcic, Slavica; Barisic, Ivan; Beketic Oreskovic, Lidija; Strbe, Sanja; Sever, Marko; Sjekavica, Ivica; Skrtic, Anita; Boban Blagaic, Alenka; Seiwerth, Sven; Sikiric, Predrag","year":2023,"journal":"World journal of gastroenterology, 29(27), 4289-4316","doi":"10.3748/wjg.v29.i27.4289","pmid":"37545637","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07024","title":"Effects of once-weekly glucagon-like peptide-1 receptor agonists on type 2 diabetes mellitus complicated with coronary artery disease: Potential role of the renin-angiotensin system.","authors":"Kan, Mengfan; Fu, Hui; Xu, Yunsheng; Yue, Zhaodi; Du, Bingyu; Chen, Qiang; Wang, Xueyin; Yu, Shaohong; Zhang, Zhongwen","year":2023,"journal":"Diabetes, obesity & metabolism, 25(11), 3223-3234","doi":"10.1111/dom.15219","pmid":"37529870","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 13 randomized controlled trials with 35,563 participants:\n\n- Dulaglutide, exenatide, and semaglutide all outperformed placebo for cardiovascular outcomes in T2DM patients with coronary artery disease\n- Significant reduction in non-fatal stroke incidence (p<0.00)\n- Significant reductions compared to conventional treatment in:\n  - HbA1c (p<0.00)\n  - Fasting blood glucose (p<0.00)\n  - Body weight (p<0.00)\n  - Systolic blood pressure (p<0.00)\n  - Total cholesterol (p<0.00)\n  - LDL cholesterol (p<0.00)\n\nNetwork pharmacology analysis identified the renin-angiotensin system as a key pathway, with matrix metalloproteinase 2 (MMP2) and renin as potential key targets. Each GLP-1 RA had distinct molecular target profiles (dulaglutide: 4 targets, exenatide: 5, semaglutide: 2).","whyItMatters":"Coronary artery disease is the leading killer of people with type 2 diabetes. This large meta-analysis provides strong evidence that once-weekly GLP-1 drugs — already prescribed for blood sugar and weight — deliver meaningful cardiovascular protection on top of their metabolic benefits. The identification of the renin-angiotensin system as a mechanistic pathway is particularly interesting because it suggests GLP-1 drugs may complement ACE inhibitors and ARBs that target the same system.","specificNumbers":"","methodology":"This was a systematic review and meta-analysis searching Chinese and English databases for randomized controlled trials of once-weekly GLP-1 RAs in T2DM patients with coronary artery disease. Pooled analyses evaluated cardiovascular outcomes and risk factor improvements. Network pharmacology analysis was used to identify potential molecular mechanisms, mapping drug targets to biological pathways.","limitations":"The meta-analysis combines trials with different designs, populations, and GLP-1 RA formulations, introducing heterogeneity. The network pharmacology analysis is computational and predictive — the identified targets (MMP2, renin) need experimental validation. The study focused only on once-weekly GLP-1 RAs, so results may not apply to daily formulations. Some of the included trials may have had different primary endpoints and follow-up periods."},{"rthcId":"RPEP-07025","title":"Efficacy of a growth hormone-releasing hormone agonist in a murine model of cardiometabolic heart failure with preserved ejection fraction.","authors":"Kanashiro-Takeuchi, Rosemeire M; Takeuchi, Lauro M; Dulce, Raul A; Kazmierczak, Katarzyna; Balkan, Wayne; Cai, Renzhi; Sha, Wei; Schally, Andrew V; Hare, Joshua M","year":2023,"journal":"American journal of physiology. Heart and circulatory physiology, 324(6), H739-H750","doi":"10.1152/ajpheart.00601.2022","pmid":"36897749","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"MR-356, a synthetic GHRH agonist, reversed multiple hallmarks of HFpEF in the cardiometabolic mouse model:\n\n- Reduced cardiac hypertrophy (heart thickening) and fibrosis (scarring)\n- Reversed capillary rarefaction (loss of small blood vessels)\n- Reduced pulmonary congestion\n- Improved diastolic function — end-diastolic pressure and the end-diastolic pressure-volume relationship were reset to control levels\n- Improved global longitudinal strain (GLS) and exercise capacity\n- Normalized elevated pro-BNP, iNOS, and VEGF-A expression, indicating reduced myocardial stress and metabolic inflammation","whyItMatters":"HFpEF accounts for roughly half of all heart failure cases and is one of the biggest unmet needs in cardiovascular medicine — there are essentially no disease-modifying therapies. The cardiometabolic phenotype (driven by obesity and metabolic dysfunction) is particularly common. Finding a peptide that reverses multiple features of this condition in a rigorous animal model is a significant preclinical advance that could lead to human trials.","specificNumbers":"","methodology":"C57BL6N mice were fed a high-fat diet combined with the nitric oxide synthase inhibitor L-NAME for 9 weeks to induce cardiometabolic HFpEF. After 5 weeks of disease induction, mice were randomized to receive daily injections of MR-356 or placebo for 4 weeks. Control mice received neither disease induction nor treatment. Cardiac function was assessed with rigorous hemodynamic tools including pressure-volume measurements, echocardiography, and exercise testing. Tissue analysis evaluated hypertrophy, fibrosis, capillary density, and molecular markers.","limitations":"This is a mouse study using a specific diet-induced model of HFpEF, which may not fully capture the complexity of human HFpEF. The treatment period was only 4 weeks, and long-term effects are unknown. The sample size is not specified in the abstract. Whether the benefits persist after treatment cessation was not tested. Human pharmacokinetics and tolerability of MR-356 may differ from the mouse model."},{"rthcId":"RPEP-07026","title":"Targeting the Arginine Vasopressin V1b Receptor System and Stress Response in Depression and Other Neuropsychiatric Disorders.","authors":"Kanes, Stephen J; Dennie, Lara; Perera, Philip","year":2023,"journal":"Neuropsychiatric disease and treatment, 19, 811-828","doi":"10.2147/NDT.S402831","pmid":"37077711","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07027","title":"Substance P, a Neuropeptide, Promotes Wound Healing via Neurokinin-1 Receptor.","authors":"Kant, Vinay; Mahapatra, Puspendra S; Gupta, Vijayta; Bag, Sadhan; Gopalakrishnan, Anu; Kumar, Dhirendra; Kumar, Dinesh","year":2023,"journal":"The international journal of lower extremity wounds, 22(2), 291-297","doi":"10.1177/15347346211004060","pmid":"33856252","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Substance P alone significantly stimulated fibroblast proliferation and migration in both scratch assays (horizontal) and transwell assays (vertical) over 24 hours. Blocking the NK-1 receptor with spantide II abolished substance P's ability to stimulate cell migration. NK-2 receptor antagonism also significantly reduced migration but was less effective than NK-1 blockade. Combined NK-1 and NK-2 antagonism produced the greatest inhibition. TGF-β1 levels were significantly elevated in substance P-treated cell supernatants, while all receptor antagonist combinations showed significantly lower TGF-β1 levels than substance P alone.","whyItMatters":"Chronic non-healing wounds (diabetic foot ulcers, pressure sores, venous leg ulcers) affect millions worldwide and cost healthcare systems billions. Understanding the specific receptor mechanism behind substance P's wound healing effects opens the door to targeted peptide-based wound therapies. If NK-1 receptor activation is the key, then substance P analogs or NK-1 agonists could be developed as topical wound treatments.","specificNumbers":"","methodology":"In vitro study using buffalo fetal fibroblast cultures. Wound healing was modeled using scratch assays (horizontal migration) and transwell assays (vertical migration). Substance P was tested alone and in combination with specific receptor antagonists: spantide II (NK-1 antagonist), an NK-2 antagonist, and both together. TGF-β1 levels in cell culture supernatants were measured by immunoassay. Cell proliferation was also assessed.","limitations":"This was an in vitro study using buffalo fetal fibroblasts, which may not perfectly represent human adult skin wound healing biology. No in vivo wound healing experiments were conducted. The study used a single cell type (fibroblasts) and did not examine substance P's effects on other wound healing cells (keratinocytes, endothelial cells, immune cells). TGF-β1 was the only growth factor measured, though substance P likely affects multiple healing mediators."},{"rthcId":"RPEP-07028","title":"GLP-1 receptor agonists and diabetic retinopathy: A meta-analysis of randomized clinical trials.","authors":"Kapoor, Ishani; Sarvepalli, Swara M; D'Alessio, David; Grewal, Dilraj S; Hadziahmetovic, Majda","year":2023,"journal":"Survey of ophthalmology, 68(6), 1071-1083","doi":"10.1016/j.survophthal.2023.07.002","pmid":"37454782","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07029","title":"Neuroprotective Action of Humanin and Humanin Analogues: Research Findings and Perspectives.","authors":"Karachaliou, Chrysoula-Evangelia; Livaniou, Evangelia","year":2023,"journal":"Biology, 12(12)","doi":"10.3390/biology12121534","pmid":"38132360","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07030","title":"Safety and efficacy of the new, oral, small-molecule, GLP-1 receptor agonists orforglipron and danuglipron for the treatment of type 2 diabetes and obesity: systematic review and meta-analysis of randomized controlled trials.","authors":"Karakasis, Paschalis; Patoulias, Dimitrios; Pamporis, Konstantinos; Stachteas, Panagiotis; Bougioukas, Konstantinos I; Klisic, Aleksandra; Fragakis, Nikolaos; Rizzo, Manfredi","year":2023,"journal":"Metabolism: clinical and experimental, 149, 155710","doi":"10.1016/j.metabol.2023.155710","pmid":"37852529","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"This meta-analysis of seven randomized controlled trials (1,037 patients total) found that the oral GLP-1 receptor agonists orforglipron and danuglipron significantly reduced HbA1c by 1.03% in people with type 2 diabetes compared to placebo. Weight loss was also significant: an average of 3.26 kg in diabetes patients and 7.52 kg in people with obesity.\n\nImportantly, the drugs did not increase the risk of severe hypoglycemia or serious adverse events. However, gastrointestinal side effects were about 2.6 times more likely, and patients were about 2.9 times more likely to stop treatment due to adverse events.","whyItMatters":"Most GLP-1 drugs like semaglutide and tirzepatide require injections. Orforglipron and danuglipron are small-molecule pills that activate the same GLP-1 receptor, which could make this class of medication far more accessible. This meta-analysis provides the first pooled look at whether these oral alternatives actually work — and suggests they do, with a safety profile broadly similar to injectable GLP-1 drugs.","specificNumbers":"","methodology":"The researchers conducted a systematic review and meta-analysis, searching PubMed, Cochrane Library, and Scopus for all randomized controlled trials of orforglipron and danuglipron published through August 2023. Two independent reviewers selected studies, extracted data, and assessed quality. Results from seven trials (1,037 patients) were pooled using random effects meta-analysis. All included trials were rated low risk of bias.","limitations":"The analysis included only seven trials with a combined 1,037 patients — a relatively small pool. Most trials were short-term, so long-term efficacy and safety remain unknown. The wide confidence interval for weight loss in people with obesity (ranging from -0.41 to -14.63 kg) suggests high variability. No data on cardiovascular outcomes or other hard endpoints were available."},{"rthcId":"RPEP-07031","title":"Biological, functional and nutritional properties of caseinomacropeptide from sweet whey.","authors":"Karimidastjerd, Atefeh; Gulsunoglu-Konuskan, Zehra","year":2023,"journal":"Critical reviews in food science and nutrition, 63(20), 4261-4273","doi":"10.1080/10408398.2021.2000360","pmid":"34802348","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07032","title":"Monoclonal Antibodies Against the Calcitonin Gene-Related Peptide and Its Receptor in Japanese Adolescents With Migraines.","authors":"Katsuki, Masahito; Kashiwagi, Kenta; Kawamura, Shin; Koh, Akihito","year":2023,"journal":"Cureus, 15(1), e33689","doi":"10.7759/cureus.33689","pmid":"36788886","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07033","title":"Real-World Efficacy of Glucagon-like Peptide-1 (GLP-1) Receptor Agonist, Dulaglutide, on Metabolic Parameters in Japanese Patients with Type 2 Diabetes: A Retrospective Longitudinal Study.","authors":"Katsuyama, Hisayuki; Hakoshima, Mariko; Umeyama, Shohei; Iida, Sakura; Adachi, Hiroki; Yanai, Hidekatsu","year":2023,"journal":"Biomedicines, 11(3)","doi":"10.3390/biomedicines11030869","pmid":"36979848","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07034","title":"Application of Cell Penetrating Peptides as a Promising Drug Carrier to Combat Viral Infections.","authors":"Khairkhah, Niloofar; Namvar, Ali; Bolhassani, Azam","year":2023,"journal":"Molecular biotechnology, 65(9), 1387-1402","doi":"10.1007/s12033-023-00679-1","pmid":"36719639","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07035","title":"A novel protective modality against rotenone-induced Parkinson's disease: A pre-clinical study with dulaglutide.","authors":"Khalaf, Marwa M; El-Sayed, Mahmoud M; Kandeil, Mohamed A; Ahmed, Sanaa","year":2023,"journal":"International immunopharmacology, 119, 110170","doi":"10.1016/j.intimp.2023.110170","pmid":"37075673","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07036","title":"Dulaglutide (Trulicity)-Induced Acute Pancreatitis: A Case Report.","authors":"Khan, Abu Baker; Shah, Aimal; Ahmad, Saad; Khan, Moiz I; Amir, Ahsan","year":2023,"journal":"Cureus, 15(5), e38630","doi":"10.7759/cureus.38630","pmid":"37284401","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A 37-year-old male with type 2 diabetes who had been taking dulaglutide 0.75 mg weekly for approximately two years developed acute pancreatitis two weeks after his dose was increased to 1.5 mg weekly. Lipase was markedly elevated at 1,508 (normal is typically <60), and CT abdomen showed peripancreatic fat stranding consistent with acute pancreatitis. Symptoms included epigastric pain radiating to the back, nausea, and vomiting — developing after his last dose of Trulicity at the higher dosage.","whyItMatters":"With millions of patients now taking GLP-1 agonists for diabetes and obesity, even rare side effects affect large numbers of people. While pancreatitis is listed as a potential risk with all GLP-1 agonists, documented cases remain scarce in the literature. This case is especially notable because the pancreatitis appeared to be triggered by a dose increase — relevant as many patients are titrated up for better glycemic control or weight loss.","specificNumbers":"","methodology":"This is a single-patient case report describing clinical presentation, laboratory findings (elevated lipase at 1,508), imaging (CT scan showing peripancreatic fat stranding), medication history, and temporal association between dulaglutide dose increase and symptom onset.","limitations":"As a single case report, this cannot establish causation — only temporal association between dulaglutide dose increase and pancreatitis. Other potential causes (gallstones, alcohol, hypertriglyceridemia) were not fully detailed in the abstract. Case reports represent the lowest level of clinical evidence and cannot determine incidence rates or population-level risk."},{"rthcId":"RPEP-07037","title":"Highly Potent Peptide Therapeutics To Prevent Protein Aggregation in Huntington's Disease.","authors":"Khan, Anooshay; Özçelik, Cemile Elif; Begli, Ozge; Oguz, Oguzhan; Kesici, Mehmet Seçkin; Kasırga, Talip Serkan; Özçubukcu, Salih; Yuca, Esra; Seker, Urartu Ozgur Safak","year":2023,"journal":"ACS medicinal chemistry letters, 14(12), 1821-1826","doi":"10.1021/acsmedchemlett.3c00415","pmid":"38116434","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The screened inhibitory peptides suppressed fibril formation in mutant huntingtin (mHtt) protein fragments, including both Htt(Q46) and Htt(Q103) — forms with 46 and 103 CAG repeats respectively. The Thioflavin T (ThT) fluorescence assay confirmed reduced fibril kinetics, and atomic force microscopy (AFM) imaging showed that the peptides prevented the characteristic fibril structures from assembling.","whyItMatters":"There is no cure for Huntington's disease and current treatments only manage symptoms. Preventing the toxic protein aggregation that drives neurodegeneration could fundamentally change how the disease is treated. Peptide-based therapies are particularly promising because they can be designed to specifically target the aggregation-prone regions of mutant huntingtin.","specificNumbers":"","methodology":"Inhibitory peptides were screened against monomeric units of wild-type huntingtin (Htt(Q25)) and two mutant fragments (Htt(Q46) and Htt(Q103)). Fibril formation kinetics were measured using the Thioflavin T (ThT) fluorescence assay, a standard method for detecting amyloid-like fibrils. Atomic force microscopy (AFM) was used to visualize how the peptides affected fibril morphology at the nanoscale.","limitations":"This is an in vitro (test tube) study only — no cell-based or animal model data were presented. The peptides have not been tested for brain penetration, stability in biological fluids, or toxicity. The jump from blocking fibril formation in a lab assay to slowing disease progression in humans is substantial and would require extensive further research."},{"rthcId":"RPEP-07038","title":"Experimental drugs for the treatment of idiopathic intracranial hypertension (IIH): shedding light on phase I and II trials.","authors":"Khatkar, Pavan; Hubbard, Jess C; Hill, Lisa; Sinclair, Alexandra J; Mollan, Susan P","year":2023,"journal":"Expert opinion on investigational drugs, 32(12), 1123-1131","doi":"10.1080/13543784.2023.2288073","pmid":"38006580","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07039","title":"Neuroendocrine metastasis to the thyroid from unknown primary and extrathyroidal disease response to peptide receptor radionuclide therapy.","authors":"Khessib, Tasnim; Khessib, Samy; Berry, Gerald; Aparici, Mari","year":2023,"journal":"Radiology case reports, 18(11), 3945-3948","doi":"10.1016/j.radcr.2023.07.044","pmid":"37680654","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A 41-year-old female underwent thyroidectomy for suspected medullary thyroid cancer, but pathology revealed a neuroendocrine tumor (NET) of unknown primary origin metastatic to the thyroid.\n\n68Ga-DOTATATE PET/CT identified somatostatin receptor-expressing lesions in: liver, right cervical nodes, thoracic paravertebral soft tissue, precoccygeal soft tissue, and right acetabulum (bone).\n\nDisease progressed on octreotide injections. The patient received 4 cycles of 177Lu-DOTATATE (Lutathera) PRRT over 8 months with:\n- No side effects or toxicities reported\n- Partial treatment response on early post-treatment scan at 6 weeks\n\nKey diagnostic lesson: somatostatin receptor PET imaging both identifies the full extent of neuroendocrine disease and predicts response to PRRT, regardless of the organ of origin.","whyItMatters":"This case illustrates two important concepts: first, that neuroendocrine tumors can mimic other cancers (initially thought to be thyroid cancer), making correct diagnosis critical for proper treatment. Second, that peptide-based imaging (68Ga-DOTATATE PET) and therapy (177Lu-DOTATATE PRRT) form a powerful 'theranostic' pair — the same peptide used for diagnosis also delivers therapy. If a tumor lights up on the diagnostic scan, it's likely to respond to the therapeutic version.","specificNumbers":"","methodology":"This is a single-patient case report documenting the clinical course of a 41-year-old female with metastatic NET of unknown primary. Diagnosis involved thyroid biopsy, thyroidectomy, and 68Ga-DOTATATE PET/CT imaging. Treatment included octreotide injections (which failed) followed by 4 cycles of 177Lu-DOTATATE PRRT. Response was assessed by post-treatment imaging at 6 weeks.","limitations":"This is a single case report — the lowest level of clinical evidence. The partial response at 6 weeks is early and long-term outcomes are unknown. NETs of unknown primary are heterogeneous, and this patient's response may not generalize. The claim of 'no side effects' over 8 months, while encouraging, differs from larger clinical trials showing that PRRT commonly causes some hematologic toxicity. No comparison to other treatment options was possible."},{"rthcId":"RPEP-07040","title":"Self-Entrapment of Antimicrobial Peptides in Silica Particles for Stable and Effective Antimicrobial Peptide Delivery System.","authors":"Ki, Mi-Ran; Kim, Sung Ho; Park, Tae In; Pack, Seung Pil","year":2023,"journal":"International journal of molecular sciences, 24(22)","doi":"10.3390/ijms242216423","pmid":"38003614","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07041","title":"Oxytocin Effect in Adult Patients with Autism: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials.","authors":"Kiani, Zahra; Farkhondeh, Tahereh; Aramjoo, Hamed; Aschner, Michael; Beydokhti, Hossein; Esmaeili, Aliakbar; Arab-Zozani, Morteza; Samarghandian, Saeed","year":2023,"journal":"CNS & neurological disorders drug targets, 22(6), 906-915","doi":"10.2174/1871527321666220517112612","pmid":"35585805","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07042","title":"Peptide Stapling with Boronate Esters- A Reversible Folding of (Artificial) Peptide Chain to α-Helix.","authors":"Kijewska, Monika; Wołczański, Grzegorz; Światowska, Marta; Kędziora, Katarzyna; Pawlicki, Miłosz; Stefanowicz, Piotr","year":2023,"journal":"Chemistry (Weinheim an der Bergstrasse, Germany), 29(40), e202301370","doi":"10.1002/chem.202301370","pmid":"37148504","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07043","title":"Vitreous hemorrhage during GLP-1 receptor agonist treatment.","authors":"Kim, Da Som; Latollari, Alisa; Khaimova, Rebecca","year":2023,"journal":"Journal of the American Pharmacists Association : JAPhA, 63(3), 976-979","doi":"10.1016/j.japh.2023.02.018","pmid":"36966088","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07044","title":"Targeted Deletion of Thymosin Beta 4 in Hepatic Stellate Cells Ameliorates Liver Fibrosis in a Transgenic Mouse Model.","authors":"Kim, Jieun; Lee, Chanbin; Han, Jinsol; Jeong, Hayeong; Wang, Sihyung; Choi, Yung Hyun; Jung, Youngmi","year":2023,"journal":"Cells, 12(12)","doi":"10.3390/cells12121658","pmid":"37371128","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07045","title":"The Novel Tetra-Specific Drug C-192, Conjugated Using UniStac, Alleviates Non-Alcoholic Steatohepatitis in an MCD Diet-Induced Mouse Model.","authors":"Kim, Jihye; Chang, Nakho; Kim, Yunki; Lee, Jaehyun; Oh, Daeseok; Choi, Jaeyoung; Kim, Onyou; Kim, Sujin; Choi, Myongho; Lee, Junyeob; Lee, Junghwa; Kim, Jungyul; Cho, Minji; Kim, Minsu; Lee, Kwanghwan; Hwang, Dukhyun; Sa, Jason K; Park, Sungjin; Baek, Seungjae; Im, Daeseong","year":2023,"journal":"Pharmaceuticals (Basel, Switzerland), 16(11)","doi":"10.3390/ph16111601","pmid":"38004466","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07046","title":"Cyclic and Linear Peptides Containing Alternate WW and RR Residues as Molecular Cargo Delivery Tools.","authors":"Kim, Lois; Lohan, Sandeep; Moreno, Jonathan; Zoghebi, Khalid; Tiwari, Rakesh Kumar; Parang, Keykavous","year":2023,"journal":"Molecular pharmaceutics, 20(1), 341-356","doi":"10.1021/acs.molpharmaceut.2c00664","pmid":"36445335","tags":[],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Researchers designed eight peptides — four linear and four cyclic — built from repeating tryptophan-tryptophan-arginine-arginine (WWRR) units and tested them as molecular delivery vehicles. The cyclic peptide [WWRR]5 (called C4) was the clear winner, showing the highest cellular uptake of three different cargo molecules including a phosphopeptide, siRNA, and an antiviral drug (3TC).\n\nNone of the peptides showed significant toxicity to cells at 5 μM concentration. The uptake of C4 was concentration- and time-dependent, and entered cells through both energy-dependent (endocytosis) and energy-independent pathways, confirming it acts as a true cell-penetrating peptide.","whyItMatters":"Many promising drugs can't get inside cells because they're too large or too negatively charged to cross cell membranes. Cell-penetrating peptides solve this by acting as molecular taxis that carry cargo across the membrane. This study's cyclic [WWRR]5 peptide successfully delivered three very different types of cargo — a peptide, an RNA molecule, and a small drug — suggesting it could be a versatile delivery platform for therapeutics that otherwise can't reach their intracellular targets.","specificNumbers":"8 peptides tested · 5 μM with no significant cytotoxicity · 3 cargo types delivered · 3 cell lines tested (MDA-MB-231, SK-OV-3, HEK 293) · 4 endocytosis inhibitors used","methodology":"Lab-based study synthesizing eight peptides (four cyclic, four linear) with alternating WW and RR residues of varying lengths. Cytotoxicity was assessed in three cell lines. Cellular uptake of fluorescence-labeled cargo was measured using flow cytometry and confocal microscopy. Endocytosis inhibitors were used to determine the uptake mechanism.","limitations":"Entirely in vitro — no animal or human testing. Tested at only one peptide concentration (5 μM) for toxicity. No comparison with established cell-penetrating peptides like TAT or penetratin. Long-term stability, immunogenicity, and in vivo behavior are unknown."},{"rthcId":"RPEP-07047","title":"Thymosin Beta 4 Protects Hippocampal Neuronal Cells against PrP (106-126) via Neurotrophic Factor Signaling.","authors":"Kim, Sokho; Choi, Jihye; Kwon, Jungkee","year":2023,"journal":"Molecules (Basel, Switzerland), 28(9)","doi":"10.3390/molecules28093920","pmid":"37175330","tags":["thymosin-beta-4","neuroprotection"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Thymosin beta 4 (Tβ4) protected hippocampal neuronal cells (HT22) against the toxic effects of the prion protein fragment PrP (106-126). Tβ4 significantly reversed the drop in cell viability and the spike in reactive oxygen species (ROS) caused by PrP (106-126). It also reduced levels of apoptotic (cell death) proteins triggered by the prion fragment.\n\nImportantly, Tβ4 maintained a competitive balance of neurotrophic factors — specifically nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) — along with their receptors (p75, TrkA, and TrkB). This suggests Tβ4 protects neurons by working through the neurotrophic factor signaling pathway rather than simply blocking the toxic peptide directly.","whyItMatters":"Prion diseases like Creutzfeldt-Jakob disease are devastating neurodegenerative conditions with no effective treatments. This study is the first to investigate whether thymosin beta 4 can protect brain cells against prion-related toxicity, opening a new research direction. The finding that Tβ4 works through neurotrophic factor pathways — the same growth factor systems that keep neurons alive and healthy — suggests it may have broader neuroprotective applications beyond prion disease.","specificNumbers":"24 h treatment · Tβ4 reversed PrP (106-126)-induced cell death · ROS levels significantly reduced · NGF, BDNF, p75, TrkA, TrkB pathways modulated","methodology":"Researchers used HT22 hippocampal neuronal cells (a mouse brain cell line) and exposed them to both thymosin beta 4 and the synthetic prion protein fragment PrP (106-126) for 24 hours. They measured cell viability, reactive oxygen species levels, apoptotic protein markers, and the expression of neurotrophic factors (NGF, BDNF) and their receptors (p75, TrkA, TrkB).","limitations":"This was an in-vitro (cell culture) study using a single mouse neuronal cell line, so results may not translate to living animals or humans. The study used a synthetic prion fragment rather than full-length prion protein, which may behave differently. No dose-response data or specific concentrations were detailed in the abstract. The 24-hour timeframe is very short and doesn't address long-term effects."},{"rthcId":"RPEP-07048","title":"Comparison of clinical efficacy and safety of weekly glucagon-like peptide-1 receptor agonists dulaglutide and semaglutide in Japanese patients with type 2 diabetes: Randomized, parallel-group, multicentre, open-label trial (COMING study).","authors":"Kimura, Tomohiko; Katakura, Yukino; Shimoda, Masashi; Kawasaki, Fumiko; Yamabe, Mizuho; Tatsumi, Fuminori; Matsuki, Michihiro; Iwamoto, Yuichiro; Anno, Takatoshi; Fushimi, Yoshiro; Kamei, Shinji; Kimura, Yukiko; Nakanishi, Shuhei; Mune, Tomoatsu; Kaku, Kohei; Kaneto, Hideaki","year":2023,"journal":"Diabetes, obesity & metabolism, 25(12), 3632-3647","doi":"10.1111/dom.15258","pmid":"37646192","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07049","title":"Semaglutide, delayed gastric emptying, and intraoperative pulmonary aspiration: a case report.","authors":"Klein, Sandra R; Hobai, Ion A","year":2023,"journal":"Canadian journal of anaesthesia = Journal canadien d'anesthesie, 70(8), 1394-1396","doi":"10.1007/s12630-023-02440-3","pmid":"36977934","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07050","title":"Thymosin β4 and the anti-fibrotic switch.","authors":"Kleinman, Hynda K; Kulik, Veronika; Goldstein, Allan L","year":2023,"journal":"International immunopharmacology, 115, 109628","doi":"10.1016/j.intimp.2022.109628","pmid":"36580759","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Thymosin beta-4 (Tβ4) prevents fibrosis and scarring in multiple animal models by reducing inflammation, decreasing macrophage infiltration, lowering levels of pro-fibrotic mediators (TGFβ, IL-10, CTGF), and preventing fibroblast conversion to myofibroblasts. The result is normally aligned collagen fibers rather than disordered scar tissue.\n\nThe N-terminal fragment of Tβ4, a tetrapeptide called Ac-SDKP (acetyl-serine-aspartate-lysine-proline), carries the majority of anti-fibrotic activity. Remarkably, Ac-SDKP can not only prevent fibrosis but also reverse established fibrosis in animal models of liver, lung, heart, and kidney fibrosis.","whyItMatters":"Fibrosis — the buildup of scar tissue in organs — is a component of many chronic diseases affecting the liver, lungs, heart, and kidneys, and currently has very limited treatment options. A peptide that can both prevent and reverse fibrosis across multiple organs would be a breakthrough therapeutic. Thymosin beta-4 and its fragment Ac-SDKP represent some of the most promising anti-fibrotic peptide candidates.","specificNumbers":"Tβ4 effective in multiple organ fibrosis models · Ac-SDKP (4 amino acids) carries majority of anti-fibrotic activity · Reduces TGFβ, IL-10, CTGF · Prevents + reverses fibrosis","methodology":"Narrative review synthesizing preclinical evidence from multiple animal models of fibrosis (liver, lung, heart, kidney) and wound healing. Covers the molecular mechanisms of Tβ4's anti-fibrotic action, including effects on macrophages, fibroblasts, and collagen organization.","limitations":"Evidence is primarily from animal models; human clinical data on anti-fibrotic applications is limited. The review does not provide quantitative comparisons of efficacy across different organ systems. Optimal dosing, delivery methods, and potential combination strategies with existing drugs remain to be fully explored."},{"rthcId":"RPEP-07051","title":"Get out or die trying: Peptide- and protein-based endosomal escape of RNA therapeutics.","authors":"Klipp, Alexander; Burger, Michael; Leroux, Jean-Christophe","year":2023,"journal":"Advanced drug delivery reviews, 200, 115047","doi":"10.1016/j.addr.2023.115047","pmid":"37536508","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07052","title":"Oral semaglutide 50 mg taken once per day in adults with overweight or obesity (OASIS 1): a randomised, double-blind, placebo-controlled, phase 3 trial.","authors":"Knop, Filip K; Aroda, Vanita R; do Vale, Ruben D; Holst-Hansen, Thomas; Laursen, Peter N; Rosenstock, Julio; Rubino, Domenica M; Garvey, W Timothy","year":2023,"journal":"Lancet (London, England), 402(10403), 705-719","doi":"10.1016/S0140-6736(23)01185-6","pmid":"37385278","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07053","title":"Modulating the folding and binding of peptides using a stimuli-responsive molecular tweezer.","authors":"Ko, Sooho; Kim, Joo-Young; Park, Jung Yeon; Jung, You-Jin; Choi, Min-Jae; Jin, Kyeong Sik; Kim, Yongju; Lim, Yong-Beom; Jeong, Woo-Jin","year":2023,"journal":"Chemical science, 14(35), 9600-9607","doi":"10.1039/d3sc03758d","pmid":"37712040","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07054","title":"Association of glucagon-like peptide-1 receptor agonist treatment with gastric residue in an esophagogastroduodenoscopy.","authors":"Kobori, Toshiko; Onishi, Yukiko; Yoshida, Yoko; Tahara, Tazu; Kikuchi, Takako; Kubota, Tetsuya; Iwamoto, Masahiko; Sawada, Tomonobu; Kobayashi, Reo; Fujiwara, Hiroaki; Kasuga, Masato","year":2023,"journal":"Journal of diabetes investigation, 14(6), 767-773","doi":"10.1111/jdi.14005","pmid":"36919944","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In propensity score-matched analysis of 205 pairs of diabetes patients, the proportion with gastric residue during esophagogastroduodenoscopy was significantly higher in GLP-1RA users: 5.4% versus 0.49% in non-users (p=0.004) — approximately an 11-fold increase.\n\nThe 11 GLP-1RA patients with gastric residue were taking various agents: liraglutide 1.8 mg daily (n=2), dulaglutide 0.75 mg weekly (n=5), semaglutide 0.5 mg weekly (n=2), and semaglutide 1.0 mg weekly (n=2). This suggests the effect is a class-wide phenomenon across different GLP-1RAs and dosing frequencies.","whyItMatters":"As GLP-1 receptor agonist use skyrockets for diabetes and weight loss, more patients on these drugs will need endoscopy, surgery, and other procedures requiring fasting and sedation. The finding that standard fasting protocols may not adequately clear the stomach in GLP-1RA users has direct implications for patient safety — food aspiration during sedation can cause pneumonia or even death. This has led to updated preprocedural fasting guidelines.","specificNumbers":"","methodology":"Matched pair case-control study of 1,128 diabetes patients who underwent esophagogastroduodenoscopy at a single Japanese clinic from July 2020 to June 2022. One-to-one propensity score matching was performed between GLP-1RA users and non-users, controlling for age, sex, insulin treatment, and HbA1c. Gastric residue presence was compared using the McNemar test. 205 matched pairs were analyzed.","limitations":"The study was conducted at a single Japanese clinic, which may limit generalizability. The overall number of patients with gastric residue was small (11 in the GLP-1RA group, 1 in controls), limiting subgroup analyses. The study could not assess whether the gastric residue caused any actual adverse events during procedures. Standard Japanese fasting protocols may differ from other countries. The study did not assess whether extending fasting times would eliminate the risk."},{"rthcId":"RPEP-07055","title":"Dairy Milk Protein-Derived Bioactive Peptides: Avengers Against Metabolic Syndrome.","authors":"Koirala, Pankaj; Dahal, Merina; Rai, Sampurna; Dhakal, Milan; Nirmal, Nilesh Prakash; Maqsood, Sajid; Al-Asmari, Fahad; Buranasompob, Athisaya","year":2023,"journal":"Current nutrition reports, 12(2), 308-326","doi":"10.1007/s13668-023-00472-1","pmid":"37204636","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07056","title":"The neuropeptide substance P/neurokinin-1 receptor system and diabetes: From mechanism to therapy.","authors":"Kokabi, Fariba; Ebrahimi, Safieh; Mirzavi, Farshad; Ghiasi Nooghabi, Nazanin; Hashemi, Seyedeh Fatemeh; Hashemy, Seyed Isaac","year":2023,"journal":"BioFactors (Oxford, England), 49(3), 534-559","doi":"10.1002/biof.1935","pmid":"36651605","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07057","title":"SNAC for Enhanced Oral Bioavailability: An Updated Review.","authors":"Kommineni, Nagavendra; Sainaga Jyothi, Vaskuri G S; Butreddy, Arun; Raju, Saka; Shapira, Tovi; Khan, Wahid; Angsantikul, Pavimol; Domb, Abraham J","year":2023,"journal":"Pharmaceutical research, 40(3), 633-650","doi":"10.1007/s11095-022-03459-9","pmid":"36539668","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07058","title":"Probiotic and intra-nasal oxytocin combination therapy on autonomic function and gut-brain axis signaling in young children and teens with autism spectrum disorder.","authors":"Kong, Xue-Jun; Kang, Jiayi; Liu, Kevin","year":2023,"journal":"Journal of psychiatric research, 166, 1-9","doi":"10.1016/j.jpsychires.2023.08.006","pmid":"37639877","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07059","title":"Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity.","authors":"Kosiborod, Mikhail N; Abildstrøm, Steen Z; Borlaug, Barry A; Butler, Javed; Rasmussen, Søren; Davies, Melanie; Hovingh, G Kees; Kitzman, Dalane W; Lindegaard, Marie L; Møller, Daniél V; Shah, Sanjiv J; Treppendahl, Marianne B; Verma, Subodh; Abhayaratna, Walter; Ahmed, Fozia Z; Chopra, Vijay; Ezekowitz, Justin; Fu, Michael; Ito, Hiroshi; Lelonek, Małgorzata; Melenovsky, Vojtech; Merkely, Bela; Núñez, Julio; Perna, Eduardo; Schou, Morten; Senni, Michele; Sharma, Kavita; Van der Meer, Peter; von Lewinski, Dirk; Wolf, Dennis; Petrie, Mark C","year":2023,"journal":"The New England journal of medicine, 389(12), 1069-1084","doi":"10.1056/NEJMoa2306963","pmid":"37622681","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07060","title":"Pharmacological Support for the Treatment of Obesity-Present and Future.","authors":"Kosmalski, Marcin; Deska, Kacper; Bąk, Bartłomiej; Różycka-Kosmalska, Monika; Pietras, Tadeusz","year":2023,"journal":"Healthcare (Basel, Switzerland), 11(3)","doi":"10.3390/healthcare11030433","pmid":"36767008","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07061","title":"Orexin antagonism and substance-P: Effects and interactions on polycystic ovary syndrome in the wistar rats.","authors":"Kouhetsani, Somayeh; Khazali, Homayoun; Rajabi-Maham, Hassan","year":2023,"journal":"Journal of ovarian research, 16(1), 89","doi":"10.1186/s13048-023-01168-4","pmid":"37147728","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07062","title":"Effects of selected blood-derived factors on innate immunity in the human body louse.","authors":"Kress, Lauren; Tegethoff, Benjamin; Pietri, Jose E","year":2023,"journal":"Transactions of the Royal Society of Tropical Medicine and Hygiene, 117(8), 546-552","doi":"10.1093/trstmh/trad011","pmid":"36919827","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07063","title":"Medication Overuse Headache, Chronic Migraine and Monoclonal Antibodies Anti-CGRP: A Real-World Study.","authors":"Krymchantowski, Abouch; Jevoux, Carla; Krymchantowski, Ana Gabriela; Silva-Néto, Raimundo Pereira","year":2023,"journal":"Clinical neuropharmacology, 46(5), 181-185","doi":"10.1097/WNF.0000000000000559","pmid":"37748000","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Eighty-eight patients with chronic migraine and medication overuse headache were divided into four groups: erenumab (19.3%), galcanezumab (29.6%), fremanezumab (25%), and conventional medications as control (26.1%). Ages ranged from 18 to 78 years (mean 44.1 ± 13.6), with 65 women and 23 men.\n\nOver 6 months of follow-up, all three anti-CGRP monoclonal antibody groups showed a statistically significant reduction in headache days compared to the conventional treatment control group (P < 0.0001).","whyItMatters":"Medication overuse headache is one of the most common and challenging complications of chronic migraine, affecting up to half of patients in specialty headache clinics. These results suggest that anti-CGRP antibodies may be particularly effective in this difficult-to-treat population, offering a way to reduce headache burden without the risks of further medication overuse.","specificNumbers":"","methodology":"This was a randomized, cross-sectional, prospective, open-label trial conducted in a real-world clinical setting. One hundred consecutive patients with chronic migraine and medication overuse headache were enrolled, with 88 completing the study. Patients were divided into four groups receiving erenumab, galcanezumab, fremanezumab, or conventional medications, and followed for 6 months.","limitations":"The study had a small sample size with only 17–26 patients per group, limiting statistical power. The open-label design means both patients and clinicians knew which treatment was being given, potentially introducing bias. The study compared different anti-CGRP antibodies against conventional treatment but did not directly compare the antibodies to each other with statistical rigor."},{"rthcId":"RPEP-07064","title":"Monoclonal antibodies for chronic migraine and medication overuse headache: A real-world study.","authors":"Krymchantowski, Abouch V; Jevoux, Carla; Krymchantowski, Ana Gabriela; Silva-Néto, Raimundo Pereira","year":2023,"journal":"Frontiers in neurology, 14, 1129439","doi":"10.3389/fneur.2023.1129439","pmid":"36937507","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In a study of 172 patients with chronic migraine and medication overuse headache, the group receiving anti-CGRP monoclonal antibodies added to conventional treatment (n=114) had a significantly greater reduction in both headache days and symptomatic medication intake at 3 months compared to the control group on conventional treatment alone (n=58), with p<0.0001.\n\nBoth groups showed improvement — indicating that the medication withdrawal and preventive treatment protocol helped on its own — but the addition of anti-CGRP antibodies provided a statistically significant additional benefit.","whyItMatters":"Medication overuse headache is one of the most challenging problems in headache medicine — patients take more painkillers to cope, which paradoxically worsens their headaches. CGRP (calcitonin gene-related peptide) is a key molecule in migraine pain signaling, and these results demonstrate that targeting this peptide with antibodies can help break the overuse cycle more effectively than standard treatments alone.","specificNumbers":"","methodology":"This was a cross-sectional, prospective, randomized, open-label study conducted in a real-world clinical setting. Two hundred patients with chronic migraine and medication overuse headache were enrolled. All patients underwent medication withdrawal and started preventive treatment. They were divided into a control group (n=58) receiving conventional treatment only and a treatment group (n=114) receiving anti-CGRP monoclonal antibodies in addition to conventional agents. Outcomes were measured at 3 months.","limitations":"This was an open-label study, meaning both patients and doctors knew who was receiving the antibody treatment, which could introduce bias. The groups were unequal in size (114 vs. 58), and the specific anti-CGRP antibody used was not detailed in the abstract. The 3-month follow-up is relatively short for a chronic condition, and longer-term outcomes remain unknown. The study was conducted at a single tertiary care center, which may treat more severe cases than typical practice."},{"rthcId":"RPEP-07065","title":"Lactoferrin and its digestive peptides induce interferon-α production and activate plasmacytoid dendritic cells ex vivo.","authors":"Kubo, Shutaro; Miyakawa, Momoko; Tada, Asuka; Oda, Hirotsugu; Motobayashi, Hideki; Iwabuchi, Sadahiro; Tamura, Shinobu; Tanaka, Miyuki; Hashimoto, Shinichi","year":2023,"journal":"Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine, 36(3), 563-573","doi":"10.1007/s10534-022-00436-y","pmid":"36018422","tags":[],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Bovine lactoferrin (LF) and its digestive peptides — including pepsin hydrolysate (LFH) and lactoferricin (LFcin) — significantly increased interferon-alpha (IFN-α) production from human immune cells when viral single-stranded RNA was present. Without viral RNA, lactoferrin had no effect on IFN-α levels, indicating it acts as an immune amplifier rather than a standalone activator.\n\nLactoferrin also upregulated expression of HLA-DR and CD86 on plasmacytoid dendritic cells (pDCs), markers of immune cell activation. The digestive peptide LFH and the antimicrobial fragment LFcin showed comparable activity, suggesting that lactoferrin retains its immune-boosting properties even after being broken down by stomach enzymes.","whyItMatters":"Lactoferrin is a naturally occurring protein in milk and other body fluids that has long been studied for antimicrobial and immune-modulating properties. This study provides a specific mechanism for how lactoferrin and its digestive fragments enhance antiviral immunity — by activating plasmacytoid dendritic cells, which are critical first responders to viral infections. The fact that digested fragments retain activity is particularly important because it suggests orally consumed lactoferrin could provide immune benefits.","specificNumbers":"LF, LFH, and LFcin all significantly increased IFN-α · LFH and LFcin effects were comparable · HLA-DR and CD86 upregulated on pDCs · Effect only present with ssRNA stimulation","methodology":"Peripheral blood mononuclear cells (PBMCs) were isolated from healthy adult donors and incubated with bovine lactoferrin, its pepsin hydrolysate (LFH), or lactoferricin (LFcin) in the presence or absence of single-stranded RNA derived from HIV. IFN-α concentrations were measured by ELISA, and expression of IFN-α, HLA-DR, and CD86 on plasmacytoid dendritic cells was quantified by flow cytometry.","limitations":"This is an ex vivo study using isolated human blood cells in a laboratory setting — results may not directly predict what happens when lactoferrin is consumed orally and passes through the full digestive and circulatory systems. The number of blood donors was not specified in the abstract. Only one type of viral stimulus (HIV-derived ssRNA) was tested, so generalizability to other viral infections is uncertain."},{"rthcId":"RPEP-07066","title":"Effect on Hemoglobin A1c (HbA1c) and Body Weight After Discontinuation of Tirzepatide, a Novel Glucose-Dependent Insulinotropic Peptide (GIP) and Glucagon-Like Peptide-1 (GLP-1) Receptor Agonist: A Single-Center Case Series Study.","authors":"Kubota, Mitsunobu; Yamamoto, Kazuki; Yoshiyama, Sayo","year":2023,"journal":"Cureus, 15(10), e46490","doi":"10.7759/cureus.46490","pmid":"37800161","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07067","title":"Continuous production of velvet bean-based bioactive peptides in membrane reactor with dual enzyme system.","authors":"Kurniadi, Nadine; Yasni, Sedarnawati; Budijanto, Slamet; Boing Sitanggang, Azis","year":2023,"journal":"Food chemistry, 423, 136378","doi":"10.1016/j.foodchem.2023.136378","pmid":"37201259","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07068","title":"Glucose-lowering effects of semaglutide compared with dulaglutide using professional continuous glucose monitoring in outpatients with type 2 diabetes mellitus: a pilot study.","authors":"Kurozumi, Akira; Okada, Yosuke; Saitoh, Momo; Tanaka, Yoshiya","year":2023,"journal":"Diabetology international, 14(4), 356-362","doi":"10.1007/s13340-023-00640-2","pmid":"37781464","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07069","title":"Dietary collagen peptides alleviate exercise-induced muscle soreness in healthy middle-aged males: a randomized double-blinded crossover clinical trial.","authors":"Kuwaba, Kumiko; Kusubata, Masashi; Taga, Yuki; Igarashi, Hiroshi; Nakazato, Koichi; Mizuno, Kazunori","year":2023,"journal":"Journal of the International Society of Sports Nutrition, 20(1), 2206392","doi":"10.1080/15502783.2023.2206392","pmid":"37133292","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07070","title":"Collagen peptides supplementation improves function, pain, and physical and mental outcomes in active adults.","authors":"Kviatkovsky, Shiloah A; Hickner, Robert C; Cabre, Hannah E; Small, Stephanie D; Ormsbee, Michael J","year":2023,"journal":"Journal of the International Society of Sports Nutrition, 20(1), 2243252","doi":"10.1080/15502783.2023.2243252","pmid":"37551682","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"At 10 g/day of collagen peptides over 6 months, significant improvements were seen in activities of daily living (p=0.031, effect size ηp²=0.096) and pain (p=0.037, ηp²=0.164), though pain improvements were limited to high-frequency exercisers (>180 min/week).\n\nMental component scores (VR-12 MCS) improved with 10 g/day over 3-9 months (p=0.017, ηp²=0.309). Physical component scores improved with 20 g/day over 3-9 months, but only in females (p=0.013, ηp²=0.582). The large effect sizes for mental health and female physical health outcomes are notable.","whyItMatters":"Chronic pain affects 19% of US adults and limits physical activity and quality of life. This is one of the longest collagen peptide supplementation studies in healthy active adults, demonstrating that a readily available, affordable supplement can meaningfully improve pain, daily function, and mental health — areas where existing interventions are often inadequate or carry side effects.","specificNumbers":"","methodology":"Double-blind randomized controlled trial with three groups: placebo, 10 g/day collagen peptides, and 20 g/day collagen peptides. Participants were middle-aged active adults assessed at 3, 6, and 9 months. Outcomes were measured using the KOOS (Knee Injury & Osteoarthritis Outcomes Score) for pain and function, and the VR-12 (Veterans Rand 12) for mental and physical health.","limitations":"Sample size for each group was not specified in the abstract, which may limit statistical power. Pain improvements required high exercise frequency (>180 min/week), limiting generalizability to less active populations. Physical health improvements at 20 g/day were only significant in females. The study did not include biomarkers of collagen metabolism or joint imaging to confirm mechanisms."},{"rthcId":"RPEP-07071","title":"Design of chimeric GLP-1A using oligomeric bile acids to utilize transporter-mediated endocytosis for oral delivery.","authors":"Kweon, Seho; Lee, Jun-Hyuck; Yang, Seong-Bin; Park, Seong Jin; Subedi, Laxman; Shim, Jung-Hyun; Cho, Seung-Sik; Choi, Jeong Uk; Byun, Youngro; Park, Jooho; Park, Jin Woo","year":2023,"journal":"Biomaterials research, 27(1), 83","doi":"10.1186/s40824-023-00421-7","pmid":"37660070","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07072","title":"In Vivo evaluation of newly synthesized 213Bi-conjugated alpha-melanocyte stimulating hormone (α-MSH) peptide analogues in melanocortin-1 receptor (MC1-R) positive experimental melanoma model.","authors":"Kálmán-Szabó, Ibolya; Képes, Zita; Fekete, Anikó; Vágner, Adrienn; Nagy, Gábor; Szücs, Dániel; Gyuricza, Barbara; Arató, Viktória; Varga, József; Kárpáti, Levente; Garai, Ildikó; Mándity, István; Bruchertseifer, Frank; Elek, János; Szikra, Dezs; Trencsényi, György","year":2023,"journal":"Journal of pharmaceutical and biomedical analysis, 229, 115374","doi":"10.1016/j.jpba.2023.115374","pmid":"37001274","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07073","title":"Modulation of hydrogel networks by metal ions.","authors":"La Manna, Sara; Florio, Daniele; Di Natale, Concetta; Marasco, Daniela","year":2023,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 29(8), e3474","doi":"10.1002/psc.3474","pmid":"36579727","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07074","title":"Administration errors of compounded semaglutide reported to a poison control center-Case series.","authors":"Lambson, Joseph E; Flegal, Samuel C; Johnson, Amberly R","year":2023,"journal":"Journal of the American Pharmacists Association : JAPhA, 63(5), 1643-1645","doi":"10.1016/j.japh.2023.06.017","pmid":"37392810","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07075","title":"Structure-Based Design and Synthesis of Stapled 10Panx1 Analogues for Use in Cardiovascular Inflammatory Diseases.","authors":"Lamouroux, Arthur; Tournier, Malaury; Iaculli, Debora; Caufriez, Anne; Rusiecka, Olga M; Martin, Charlotte; Bes, Viviane; Carpio, Laureano E; Girardin, Yana; Loris, Remy; Tabernilla, Andrés; Molica, Filippo; Gozalbes, Rafael; Mayán, María D; Vinken, Mathieu; Kwak, Brenda R; Ballet, Steven","year":2023,"journal":"Journal of medicinal chemistry, 66(18), 13086-13102","doi":"10.1021/acs.jmedchem.3c01116","pmid":"37703077","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Stapled (macrocyclic) analogues of the Pannexin1-blocking peptide 10Panx1 were developed with dramatically improved properties. Two analogues (SBL-PX1-42 and SBL-PX1-44) achieved 2-fold greater Panx1 channel inhibition compared to the native linear peptide and showed >30-fold longer half-lives in human plasma. A double-stapled variant (SBL-PX1-206) inhibited ATP release from endothelial cells and significantly reduced monocyte adhesion to inflamed endothelium, demonstrating potential for treating cardiovascular inflammatory disease.","whyItMatters":"Pannexin1 channels release ATP during inflammation, driving immune cell recruitment to blood vessel walls — a key step in cardiovascular diseases like atherosclerosis. While 10Panx1 is the go-to peptide tool for blocking these channels, it breaks down too quickly in the body to be a drug. This study transforms it into a stable, more potent macrocyclic compound with real therapeutic potential, advancing peptide-based approaches to cardiovascular inflammation.","specificNumbers":"","methodology":"Researchers used structure-based rational design to create macrocyclic (stapled) analogues of the 10Panx1 peptide using triazole-based cross-links. They tested the compounds in vitro using ATP release assays, Yo-Pro-1 uptake assays in Panx1-expressing tumor cells, proteolytic stability assays in human plasma, and monocyte adhesion assays using THP-1 cells on TNF-α-activated endothelial monolayers.","limitations":"All testing was in vitro — no animal or human studies were conducted. The endothelial adhesion assays used cell lines, which may not fully replicate the complexity of vascular inflammation in vivo. Selectivity over other pannexin family members and connexins was not thoroughly characterized. The double-stapled compound (SBL-PX1-206) needs in vivo validation to confirm its therapeutic potential."},{"rthcId":"RPEP-07076","title":"D-Peptide and D-Protein Technology: Recent Advances, Challenges, and Opportunities.","authors":"Lander, Alexander J; Jin, Yi; Luk, Louis Y P","year":2023,"journal":"Chembiochem : a European journal of chemical biology, 24(4), e202200537","doi":"10.1002/cbic.202200537","pmid":"36278392","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07077","title":"Collagen Hydrolysates: A Source of Bioactive Peptides Derived from Food Sources for the Treatment of Osteoarthritis.","authors":"Larder, Christina E; Iskandar, Michèle M; Kubow, Stan","year":2023,"journal":"Medicines (Basel, Switzerland), 10(9)","doi":"10.3390/medicines10090050","pmid":"37755240","tags":["collagen-peptides","osteoarthritis","joint-health"],"studyType":"Review","evidenceStrength":"Moderate","keyFinding":"Collagen hydrolysates (CHs) — low molecular weight peptides (3–6 kDa) from industrially processed collagen — have shown positive results in clinical trials for osteoarthritis: decreased joint pain, increased mobility, and structural joint improvements. The biological activity comes from bioactive peptides released during digestion of the collagen hydrolysate.\n\nHowever, the review identifies significant knowledge gaps: it's unclear how well these peptides survive digestion, how much actually reaches the joints (bioavailability), which specific peptide sequences are responsible for the benefits, and how different collagen hydrolysate products compare. Sources include bovine (most common), porcine, and fish (piscine) collagen, each potentially producing different bioactive peptide profiles.","whyItMatters":"Osteoarthritis affects over 300 million people worldwide and has no effective medications that modify disease progression — only pain management. Collagen hydrolysates are among the most popular supplements taken by OA patients, with global sales in the billions. This review assesses the evidence base for this massive consumer trend: clinical trials show real benefits, but the mechanisms are poorly understood and product quality varies enormously.","specificNumbers":"Peptides typically 3–6 kDa · bovine, porcine, piscine sources · clinical trial evidence for: reduced pain, increased mobility, structural improvements · significant bioavailability and digestion knowledge gaps","methodology":"Narrative review assessing collagen hydrolysates as OA treatments, covering sources and manufacturing, bioactive peptide content, clinical trial evidence for joint health benefits, and knowledge gaps in digestion, bioavailability, and bioactivity.","limitations":"The review acknowledges that understanding of CH-derived bioactive peptides remains incomplete — particularly regarding which specific peptides drive the clinical benefits and how they survive digestion to reach joint tissue. Different CH products may produce different peptide profiles, making it difficult to compare studies. The review does not perform a systematic quality assessment of the clinical trials cited. Some positive clinical trials may have been industry-funded."},{"rthcId":"RPEP-07078","title":"ApoE Mimetic Peptides as Therapy for Traumatic Brain Injury.","authors":"Laskowitz, Daniel T; Van Wyck, David W","year":2023,"journal":"Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 20(6), 1496-1507","doi":"10.1007/s13311-023-01413-0","pmid":"37592168","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07079","title":"Activation of TLRs Triggers GLP-1 Secretion in Mice.","authors":"Lebrun, Lorène J; Dusuel, Alois; Xolin, Marion; Le Guern, Naig; Grober, Jacques","year":2023,"journal":"International journal of molecular sciences, 24(6)","doi":"10.3390/ijms24065333","pmid":"36982420","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07080","title":"Systemic C-peptide supplementation ameliorates retinal neurodegeneration by inhibiting VEGF-induced pathological events in diabetes.","authors":"Lee, Ah-Jun; Moon, Chan-Hee; Lee, Yeon-Ju; Jeon, Hye-Yoon; Park, Won Sun; Ha, Kwon-Soo","year":2023,"journal":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 37(2), e22763","doi":"10.1096/fj.202201390RR","pmid":"36625326","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07081","title":"Clinical Characteristics Associated with Adherence and Persistence in Patients with Type 2 Diabetes Mellitus Treated with Dulaglutide.","authors":"Lee, David Seung U; Lee, Howard","year":2023,"journal":"Journal of diabetes research, 2023, 7917641","doi":"10.1155/2023/7917641","pmid":"37305431","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 236 dulaglutide users followed for one year, increasing age and higher estimated glomerular filtration rate (eGFR) significantly increased both adherence and treatment continuation. Baseline obesity and baseline use of sulfonylurea or insulin significantly reduced the likelihood of continuing dulaglutide.\n\nSwitching dulaglutide dose during treatment and baseline neuropathy were associated with higher proportion of days covered (PDC) and longer treatment duration. In patients at high cardiovascular risk, baseline hypertension and higher LDL-C levels increased the likelihood of adherence. Cardiovascular risk status itself did not significantly affect any adherence or persistence outcome.","whyItMatters":"GLP-1 receptor agonists like dulaglutide only work if patients keep taking them. Understanding which patients are likely to stop — and why — helps clinicians provide targeted support. The finding that obese patients and those on insulin or sulfonylureas are more likely to discontinue suggests these groups may need closer monitoring and encouragement, potentially preventing the metabolic consequences of stopping GLP-1 therapy.","specificNumbers":"","methodology":"This was a retrospective observational cohort study using the Common Data Model at Seoul National University Hospital. The 236 eligible patients with type 2 diabetes treated with dulaglutide were followed for one year. Researchers used multivariate logistic regression for categorical outcomes (adherence status, continuation status) and linear regression for continuous outcomes (proportion of days covered, treatment duration). A subgroup analysis examined patients at high cardiovascular risk, defined as having two or more identifiable risk factors.","limitations":"This was a single-center retrospective study at one Korean hospital, limiting generalizability to other populations. The sample size of 236 is relatively small. Reasons for discontinuation (e.g., side effects, cost, patient preference) were not captured. The study used a one-year follow-up period, which may not capture longer-term adherence patterns. The Common Data Model approach relies on pharmacy records, which may not perfectly reflect actual medication use."},{"rthcId":"RPEP-07082","title":"Glucometabolic control of once-weekly dulaglutide switched from DPP4 inhibitor versus daily empagliflozin add-on in patients with type 2 diabetes inadequately controlled with metformin, sulfonylurea, and DPP4 inhibitor: A randomised trial.","authors":"Lee, Eun Young; Cho, Jae-Hyoung; Lee, Woo Je; Kim, Nam Hoon; Kim, Jae Hyeon; Lee, Byung-Wan","year":2023,"journal":"Diabetes research and clinical practice, 203, 110884","doi":"10.1016/j.diabres.2023.110884","pmid":"37595844","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07083","title":"AMP-BERT: Prediction of antimicrobial peptide function based on a BERT model.","authors":"Lee, Hansol; Lee, Songyeon; Lee, Ingoo; Nam, Hojung","year":2023,"journal":"Protein science : a publication of the Protein Society, 32(1), e4529","doi":"10.1002/pro.4529","pmid":"36461699","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"AMP-BERT, a deep learning model based on the BERT transformer architecture, outperformed all other machine learning and deep learning methods at predicting whether a peptide sequence has antimicrobial activity. The model was fine-tuned to extract structural and functional features from peptide sequences and classify them as antimicrobial or non-antimicrobial. Using BERT's attention mechanism, the researchers also identified specific amino acid residues that contribute most to antimicrobial function, providing interpretable insights into what makes a peptide antimicrobial.","whyItMatters":"Discovering new antimicrobial peptides through lab experiments is slow and expensive. AI models like AMP-BERT can rapidly screen millions of peptide sequences computationally, flagging the most promising candidates for lab testing. This accelerates the search for new antibiotics at a time when antimicrobial resistance is making existing drugs less effective. The interpretability feature also helps researchers understand why certain peptides work, guiding rational design.","specificNumbers":"","methodology":"The researchers fine-tuned a bidirectional encoder representations from transformers (BERT) model — a type of deep learning architecture originally developed for language processing — on datasets of known antimicrobial and non-antimicrobial peptide sequences. They compared AMP-BERT's classification accuracy against other machine learning and deep learning approaches using a curated external test dataset. They also used BERT's attention mechanism to analyze which amino acid positions were most important for the model's predictions.","limitations":"The model classifies peptides as antimicrobial or non-antimicrobial but does not predict potency, spectrum of activity, or toxicity to human cells. Predictions are computational and require experimental validation. The training data reflects known AMPs, which may bias the model toward familiar peptide types. Performance on highly novel or unusual peptide structures is uncertain."},{"rthcId":"RPEP-07084","title":"Altered Hippocampal and Striatal Expression of Endothelial Markers and VIP/PACAP Neuropeptides in a Mouse Model of Systemic Lupus Erythematosus.","authors":"Lee, Jayden; Thomas Broome, Sarah; Jansen, Margo Iris; Mandwie, Mawj; Logan, Grant J; Marzagalli, Rubina; Musumeci, Giuseppe; Castorina, Alessandro","year":2023,"journal":"International journal of molecular sciences, 24(13)","doi":"10.3390/ijms241311118","pmid":"37446298","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In NZBWF1 lupus mice compared to controls:\n\n**Hippocampus**: Mild endothelial dysfunction markers (altered tPA, uPA, ICAM-1, VCAM-1, eNOS, KLF4) that worsened with age (2 vs. 7 months). VIP/PACAP system showed moderate changes.\n\n**Striatum**: Robust endothelial activation markers even in young mice, with significant upregulation of the VIP/PACAP system including VIP, PACAP, and their receptors (PAC1, VPAC1, VPAC2). This suggests the striatum is more vulnerable to lupus-related vascular damage.\n\nThe key insight: the brain's endogenous neuropeptide defense system (VIP/PACAP) is activated in response to vascular damage but cannot effectively counteract the ongoing autoimmune injury.","whyItMatters":"Neuropsychiatric lupus (NPSLE) affects up to 75% of lupus patients but remains poorly understood and hard to treat. This study reveals that brain blood vessel damage is a key pathogenic mechanism and identifies the VIP/PACAP system as an endogenous protective response. This opens the door to therapeutic strategies using exogenous VIP or PACAP peptides — or their analogs — to boost the brain's natural defense against lupus-related vascular injury.","specificNumbers":"","methodology":"Researchers used NZBWF1 mice (a spontaneous lupus model) at 2 months (pre-disease) and 7 months (active disease) of age. Gene and protein expression of endothelial markers (tPA, uPA, ICAM-1, VCAM-1, BDNF, eNOS, KLF4) and neuropeptide system components (VIP, PACAP, PAC1, VPAC1, VPAC2) were measured in dissected hippocampus and striatum using qPCR and protein analysis techniques.","limitations":"The study was conducted in mice, and the NZBWF1 model may not fully replicate all features of human NPSLE. Only two time points were assessed. Functional outcomes (behavior, cognition, blood-brain barrier permeability) were not directly measured. The study identified correlations between endothelial dysfunction and neuropeptide changes but did not establish causation or test whether exogenous VIP/PACAP could prevent the damage."},{"rthcId":"RPEP-07085","title":"Valorization of leftover green tea residues through conversion to bioactive peptides using probiotics-aided anaerobic digestion.","authors":"Lee, Ji-Young; Hong, Hyein; Lee, Jae-Eun; Hong, Yi-Jee; Hwang, Hye Won; Jin, Hyeon-Su; Shim, Hyunkyou; Hong, Yong-Deog; Park, Won-Seok; Chung, Jin-Oh; Lee, Dong-Woo","year":2023,"journal":"Microbial biotechnology, 16(2), 418-431","doi":"10.1111/1751-7915.14155","pmid":"36285915","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07086","title":"New migraine prophylactic drugs: Current evidence and practical suggestions for non-responders to prior therapy.","authors":"Lee, Mi Ji; Al-Karagholi, Mohammad Al-Mahdi; Reuter, Uwe","year":2023,"journal":"Cephalalgia : an international journal of headache, 43(2), 3331024221146315","doi":"10.1177/03331024221146315","pmid":"36759320","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"High-quality evidence supports all four available anti-CGRP receptor monoclonal antibodies (erenumab, galcanezumab, fremanezumab, and eptinezumab) for migraine prevention in patients who have failed prior prophylactic therapies. Switching from one anti-CGRP antibody to another may benefit some non-responders. Evidence is currently insufficient to confirm or reject the efficacy of combining CGRP-targeting drugs with oral prophylactics or botulinum toxin A. Treatment termination strategies remain guided primarily by reimbursement policies rather than clinical evidence.","whyItMatters":"Before CGRP-targeting drugs, many migraine patients cycled through repurposed medications (blood pressure drugs, antidepressants, anticonvulsants) that weren't designed for migraine and often failed or caused intolerable side effects. CGRP-targeting therapies are the first migraine-specific preventive drugs, representing a paradigm shift. This review addresses the practical questions clinicians face when using these drugs in patients with the most treatment-resistant migraines.","specificNumbers":"","methodology":"Narrative review of published literature on CGRP-targeting migraine prophylactics, focusing on real-world clinical scenarios: non-response to prior therapy, combination therapy, switching between drugs, and treatment termination. Where published evidence was lacking, the authors provided recommendations based on clinical reasoning and expert opinion.","limitations":"This is a narrative review, not a systematic review or meta-analysis, so the evidence selection may be subject to author bias. Much of the practical guidance on switching, combining, and terminating treatment is based on clinical reasoning rather than randomized controlled trials. Real-world effectiveness may differ from clinical trial results. The review acknowledges that evidence gaps remain significant for several key clinical questions."},{"rthcId":"RPEP-07087","title":"Oral intake of collagen peptide NS improves hydration, elasticity, desquamation, and wrinkling in human skin: a randomized, double-blinded, placebo-controlled study.","authors":"Lee, Miyeong; Kim, Eunjoung; Ahn, Hyunwoo; Son, Seokjun; Lee, Hyunjun","year":2023,"journal":"Food & function, 14(7), 3196-3207","doi":"10.1039/d2fo02958h","pmid":"36916504","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Daily oral intake of 1,650 mg of collagen peptide NS (CPNS) — rich in the bioactive dipeptides Gly-Pro and Pro-Hyp — produced statistically significant improvements in multiple skin health markers compared to placebo.\n\nSkin desquamation (flaking) and hydration showed early improvements, reaching significance at 4 weeks. Skin wrinkling and elasticity required a longer treatment period, achieving significance at 12 weeks. The staggered timeline suggests collagen peptides may first address surface-level moisture and barrier function before influencing deeper structural properties like elasticity.","whyItMatters":"Collagen supplements are one of the most popular categories in the peptide and beauty supplement market, but rigorous clinical evidence has been uneven. This well-designed RCT provides strong support for oral collagen peptides improving measurable skin outcomes, with a clear dose, timeline, and safety profile — the kind of data consumers and clinicians need to evaluate these products.","specificNumbers":"n=100 · 1,650 mg/day CPNS · 12 weeks · hydration improved at 4 weeks · elasticity improved at 12 weeks · 0 side effects reported","methodology":"This was a randomized, double-blind, placebo-controlled clinical trial involving 100 women aged 30 to 60. Participants were assigned to either the collagen peptide group (1,650 mg/day of CPNS) or a placebo group for 12 weeks. Researchers measured skin hydration, elasticity, desquamation, and wrinkling at multiple time points throughout the study.","limitations":"The study was conducted in a single cohort of women aged 30–60, so results may not generalize to men or younger/older populations. The specific brand formulation (CPNS) may differ from other collagen products on the market. The 12-week duration leaves long-term maintenance effects unknown, and the study did not report effect sizes or confidence intervals in the abstract."},{"rthcId":"RPEP-07088","title":"Antimicrobial peptides β-defensin family: Expression and regulation in the endometrium during the estrous cycle and pregnancy in pigs.","authors":"Lee, Soohyung; Yoo, Inkyu; Cheon, Yugyeong; Hong, Minsun; Jeon, Bo-Young; Ka, Hakhyun","year":2023,"journal":"Developmental and comparative immunology, 139, 104596","doi":"10.1016/j.dci.2022.104596","pmid":"36442607","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07089","title":"Aspirin induces immunogenic cell death and enhances cancer immunotherapy in colorectal cancer.","authors":"Lei, Jun; Zhou, Zihao; Fang, Jialing; Sun, Zaiqiao; He, Mengting; He, Boxiao; Chen, Qian; Paek, Chonil; Chen, Peng; Zhou, Jin; Wang, Hongjian; Tang, Mingliang; Yin, Lei; Chen, Yongshun","year":2023,"journal":"International immunopharmacology, 121, 110350","doi":"10.1016/j.intimp.2023.110350","pmid":"37290325","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07090","title":"Effect of dulaglutide in promoting abstinence during smoking cessation: a single-centre, randomized, double-blind, placebo-controlled, parallel group trial.","authors":"Lengsfeld, Sophia; Burkard, Thilo; Meienberg, Andrea; Jeanloz, Nica; Vukajlovic, Tanja; Bologna, Katja; Steinmetz, Michelle; Bathelt, Cemile; Sailer, Clara O; Vogt, Deborah R; Hemkens, Lars G; Speich, Benjamin; Urwyler, Sandrine A; Kühne, Jill; Baur, Fabienne; Lutz, Linda N; Erlanger, Tobias E; Christ-Crain, Mirjam; Winzeler, Bettina","year":2023,"journal":"EClinicalMedicine, 57, 101865","doi":"10.1016/j.eclinm.2023.101865","pmid":"36874396","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07091","title":"SOS1-inspired hydrocarbon-stapled peptide as a pan-Ras inhibitor.","authors":"Li, Anpeng; Li, Xiang; Zou, Jihua; Zhuo, Xiaobin; Chen, Shuai; Chai, Xiaoyun; Gai, Conghao; Xu, Weiheng; Zhao, Qingjie; Zou, Yan","year":2023,"journal":"Bioorganic chemistry, 135, 106500","doi":"10.1016/j.bioorg.2023.106500","pmid":"37003134","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07092","title":"Comparative yields of antimicrobial peptides released from human and cow milk proteins under infant digestion conditions predicted by in silico methodology.","authors":"Li, Feijie; Dhordain, Pauline; Hearn, Milton T W; Martin, Lisandra L; Bennett, Louise E","year":2023,"journal":"Food & function, 14(11), 5442-5452","doi":"10.1039/d3fo00748k","pmid":"37227320","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07093","title":"Epidermal Growth Factor Receptor-Targeted Neoantigen Peptide Vaccination for the Treatment of Non-Small Cell Lung Cancer and Glioblastoma.","authors":"Li, Fenge; Wu, Huancheng; Du, Xueming; Sun, Yimo; Rausseo, Barbara Nassif; Talukder, Amjad; Katailiha, Arjun; Elzohary, Lama; Wang, Yupeng; Wang, Zhiyu; Lizée, Gregory","year":2023,"journal":"Vaccines, 11(9)","doi":"10.3390/vaccines11091460","pmid":"37766136","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07094","title":"Clinical evidence of the efficacy and safety of a new multi-peptide anti-aging topical eye serum.","authors":"Li, Fengzhu; Chen, Haowei; Chen, Dongxiao; Zhang, Bingjie; Shi, Qingying; He, Xihong; Zhao, Huabing; Wang, Fang","year":2023,"journal":"Journal of cosmetic dermatology, 22(12), 3340-3346","doi":"10.1111/jocd.15849","pmid":"37335808","tags":[],"studyType":"clinical trial","evidenceStrength":"low","keyFinding":"A topical eye serum containing multiple bioactive peptides significantly reduced wrinkles around the eyes after 28 days of daily use in 32 women aged 20-45. The study documented decreases in wrinkle number, depth, and volume in the crow's feet area, along with improvements in skin hydration, elasticity, and firmness that increased continuously throughout the study period. 75% of participants expressed overall satisfaction with their skin appearance after using the product, and no adverse reactions were reported.","whyItMatters":"Cosmetic peptides are one of the fastest-growing segments of the skincare industry, but clinical data supporting their efficacy has often lagged behind marketing claims. This study provides objective instrumental measurements — not just subjective reports — showing that a multi-peptide formulation can measurably improve wrinkle parameters and skin quality metrics around the eye area over a 28-day period.","specificNumbers":"n=32, average age 28.5 years, 28 days of use, 75% overall satisfaction","methodology":"Thirty-two female subjects (average age 28.5) applied the multi-peptide eye serum daily for 28 days. Researchers measured skin hydration with a Corneometer CM825, skin elasticity with a Skin Elastometer MPA580, and wrinkle parameters (number, depth, volume) around the crow's feet area using PRIMOS CR digital strip projection imaging. Self-assessment questionnaires were completed on Days 14 and 28.","limitations":"This was a small, open-label study with no placebo or control group, making it impossible to distinguish the peptide effects from the moisturizing effects of the serum base. The sample size of 32 was modest, and the average participant age of 28.5 is young for an anti-aging study, where wrinkles are typically less pronounced. The 28-day duration is relatively short. The specific peptides in the formulation are not named in the abstract."},{"rthcId":"RPEP-07095","title":"CycPeptMPDB: A Comprehensive Database of Membrane Permeability of Cyclic Peptides.","authors":"Li, Jianan; Yanagisawa, Keisuke; Sugita, Masatake; Fujie, Takuya; Ohue, Masahito; Akiyama, Yutaka","year":2023,"journal":"Journal of chemical information and modeling, 63(7), 2240-2250","doi":"10.1021/acs.jcim.2c01573","pmid":"36930969","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07096","title":"A cell-penetrating PHLPP peptide improves cardiac arrest survival in murine and swine models.","authors":"Li, Jing; Zhu, Xiangdong; Oberdier, Matt T; Lee, Chunpei; Lin, Shaoxia; Fink, Sarah J; Justice, Cody N; Qin, Kevin; Begeman, Andrew W; Damen, Frederick C; Kim, Hajwa; Chen, Jiwang; Cai, Kejia; Halperin, Henry R; Vanden Hoek, Terry L","year":2023,"journal":"The Journal of clinical investigation, 133(9)","doi":"10.1172/JCI164283","pmid":"37115695","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"TAT-PHLPP9c, a 20-amino acid cell-penetrating peptide, administered intravenously during CPR after 12-minute asystolic arrest in mice significantly improved return of spontaneous circulation, mean arterial blood pressure, cerebral blood flow, cardiac and neurological function, and survival at both 4 hours and 5 days.\n\nMechanistically, the peptide works by inhibiting PHLPP1, enhancing AKT activation (but not PKC), decreasing pyruvate dehydrogenase phosphorylation and sorbitol production, and increasing ATP generation in heart and brain. It also reduced plasma taurine and glutamate — markers of cell damage. Critically, these protective benefits were validated in a swine model of ventricular fibrillation cardiac arrest, providing strong translational evidence.","whyItMatters":"Out-of-hospital cardiac arrest has a mortality rate exceeding 90%, and despite decades of research, no medication improves long-term survival. Therapeutic cooling helps but is extremely difficult to implement in emergency settings. A simple IV injection that mimics cooling's protective effects could be administered by paramedics during CPR — potentially saving hundreds of thousands of lives annually worldwide.","specificNumbers":"","methodology":"Complementary studies in mouse and swine cardiac arrest models. C57BL/6 mice were randomized (blinded) into saline control and peptide-treatment groups after 12-minute asystolic arrest, with TAT-PHLPP9c administered IV during CPR. Outcomes included return of circulation, blood pressure, cerebral blood flow, cardiac and neurological function, and survival (4-hour and 5-day). Biochemical analyses measured PHLPP signaling, AKT/PKC phosphorylation, metabolic markers, and plasma biomarkers. Validation was performed in a swine ventricular fibrillation arrest model.","limitations":"This is preclinical research in animals, not humans. While the swine model provides strong translational evidence, human cardiac arrest involves additional complexities (comorbidities, variable arrest times, bystander CPR quality). The optimal dose, timing window, and safety profile in humans have not been established. The study used controlled laboratory conditions that differ from real-world emergency scenarios."},{"rthcId":"RPEP-07097","title":"ACE-Inhibitory Peptides Identified from Quinoa Bran Glutelin-2 Hydrolysates: In Silico Screening and Characterization, Inhibition Mechanisms of ACE, Coordination with Zinc Ions, and Stability.","authors":"Li, Junru; Huo, Xinyu; Zheng, Yajun; Guo, Yizi; Feng, Chen","year":2023,"journal":"Plant foods for human nutrition (Dordrecht, Netherlands), 78(2), 419-425","doi":"10.1007/s11130-023-01074-6","pmid":"37300747","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07098","title":"Light Chain Q166C Mutation Permits One-step Site Specific Conjugation on Monoclonal Antibodies.","authors":"Li, Mingying; Song, Chunyu; Li, Jiayun; Min, Junting; Cao, Lei; Wang, Lin; Ma, Ningning","year":2023,"journal":"Chembiochem : a European journal of chemical biology, 24(13), e202200780","doi":"10.1002/cbic.202200780","pmid":"37079449","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07099","title":"Campylobacter jejuni infection induces dynamic expression of avian host defense peptides in vitro and in vivo.","authors":"Li, Pengxiang; Cui, Yifang; Guo, Fangfang; Guo, Jiahui; Cao, Xiaoya; Lin, Jun; Ding, Baoan; Xu, Fuzhou","year":2023,"journal":"Veterinary microbiology, 277, 109631","doi":"10.1016/j.vetmic.2022.109631","pmid":"36543091","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07100","title":"Therapeutic Peptides for Treatment of Lung Diseases: Infection, Fibrosis, and Cancer.","authors":"Li, Shujiao; Li, Yuying; Liu, Ying; Wu, Yifan; Wang, Qiuyu; Jin, Lili; Zhang, Dianbao","year":2023,"journal":"International journal of molecular sciences, 24(10)","doi":"10.3390/ijms24108642","pmid":"37239989","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07101","title":"The preliminary study of exosomes derived from thymosin beta 4-treated adipose-derived stem cells in fat grafting.","authors":"Li, Wandi; Yang, Yan; Zhang, Xiaoyu; Lin, Yan; Li, Haoran; Yao, Yu; Mu, Dali","year":2023,"journal":"Genes & genomics, 45(4), 413-427","doi":"10.1007/s13258-022-01329-7","pmid":"36445571","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07102","title":"Structure-Activity Relationship of Novel ACE Inhibitory Undecapeptides from Stropharia rugosoannulata by Molecular Interactions and Activity Analyses.","authors":"Li, Wen; Chen, Wanchao; Wang, Jinbin; Li, Zhengpeng; Zhang, Zhong; Wu, Di; Yan, Mengqiu; Ma, Haile; Yang, Yan","year":2023,"journal":"Foods (Basel, Switzerland), 12(18)","doi":"10.3390/foods12183461","pmid":"37761171","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"From 27 undecapeptides screened by molecular docking, GQEDYDRLRPL was identified as the best ACE inhibitor from S. rugosoannulata. Ten of its eleven amino acid residues interacted with the ACE receptor. The peptide bound ACE with strong affinity — kinetic binding constant of 9.26 × 10⁻⁷ M and thermodynamic binding constant of 3.06 × 10⁻⁶ M. Binding was exothermic and enthalpy-driven.\n\nThe peptide had an in vitro IC50 of 164.41 μmol/L for ACE inhibition. In vivo, oral gavage administration at low doses showed superior antihypertensive effects compared to controls. Molecular dynamics simulations revealed that the peptide caused significant structural fluctuations in ACE residues 340-355, which include two residues in the enzyme's active pocket.","whyItMatters":"Hypertension affects over a billion people worldwide, and while ACE inhibitor drugs are effective, natural food-derived alternatives are increasingly sought for their potential as functional foods or supplements with fewer side effects. This mushroom-derived peptide demonstrates that edible fungi can be sources of potent ACE-inhibitory peptides, and the comprehensive structure-activity analysis provides a framework for optimizing such peptides.","specificNumbers":"","methodology":"Twenty-seven undecapeptides from S. rugosoannulata were screened using molecular docking against the ACE receptor. The lead peptide GQEDYDRLRPL was characterized using molecular dynamics simulations, surface plasmon resonance (for kinetic binding), isothermal titration calorimetry (for thermodynamic binding), and in vitro ACE inhibition assays. Antihypertensive activity was validated in vivo through low-dose oral gavage in animals.","limitations":"The IC50 of 164.41 μmol/L is relatively high compared to pharmaceutical ACE inhibitors (which work at nanomolar concentrations). It is unclear whether the peptide survives complete gastrointestinal digestion in its active form. The in vivo antihypertensive data is not detailed in the abstract (specific blood pressure reductions and animal model not described). Long-term safety and efficacy data are not available."},{"rthcId":"RPEP-07103","title":"Study on the In Silico Screening and Characterization, Inhibition Mechanisms, Zinc-Chelate Activity, and Stability of ACE-Inhibitory Peptides Identified in Naked Oat Bran Albumin Hydrolysates.","authors":"Li, Yan; Li, Junru; Cheng, Chaoxia; Zheng, Yajun; Li, Hanxu; Zhu, Zilin; Yan, Yuxiang; Hao, Wenhui; Qin, Nan","year":2023,"journal":"Foods (Basel, Switzerland), 12(11)","doi":"10.3390/foods12112268","pmid":"37297512","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07104","title":"Lycorine transfersomes modified with cell-penetrating peptides for topical treatment of cutaneous squamous cell carcinoma.","authors":"Li, Ying; Tai, Zongguang; Ma, Jinyuan; Miao, Fengze; Xin, Rujuan; Shen, Cuie; Shen, Min; Zhu, Quangang; Chen, Zhongjian","year":2023,"journal":"Journal of nanobiotechnology, 21(1), 139","doi":"10.1186/s12951-023-01877-4","pmid":"37118807","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07105","title":"Vasoactive intestinal peptide exerts therapeutic action by regulating PTEN in a model of Sjögren's disease.","authors":"Li, Yixi; Zhu, Wen; Lin, Rui; Zhao, Junjie; Wang, Yue","year":2023,"journal":"Immunity, inflammation and disease, 11(7), e936","doi":"10.1002/iid3.936","pmid":"37506142","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07106","title":"Isolation and identification of angiotensin-converting enzyme inhibitory peptides from Tartary buckwheat albumin.","authors":"Li, Yongfu; Yang, Nan; Shi, Feng; Ye, Fei; Huang, Jinrong","year":2023,"journal":"Journal of the science of food and agriculture, 103(10), 5019-5027","doi":"10.1002/jsfa.12573","pmid":"36967483","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Four protein fractions from Tartary buckwheat (albumin, globulin, prolamin, glutelin) were hydrolyzed with pepsin and trypsin. All showed ACE inhibitory activity, with albumin hydrolysate (AH) strongest:\n\n- AH: 79.89% ACE inhibition at 0.2 mg/mL with the highest peptide yield (82.28%)\n- Globulin hydrolysate: 71.84% inhibition\n- Prolamin and glutelin hydrolysates: lower inhibition rates\n\nAfter gel filtration and reversed-phase HPLC purification of the most active AH fraction, nano-LC-MS/MS identified 42 ACE inhibitory peptides. Of these, 14 were completely novel discoveries. Computational analysis confirmed potent ACE inhibitory potential for all 14 new peptides.","whyItMatters":"ACE inhibitor drugs (like lisinopril and enalapril) are among the most prescribed medications worldwide for hypertension. Finding natural food-derived ACE inhibitory peptides could lead to functional foods or supplements that support blood pressure management as part of a healthy diet. Tartary buckwheat is particularly attractive because it's already consumed as food in many Asian countries and is gaining popularity as a health food globally.","specificNumbers":"","methodology":"Albumin, globulin, prolamin, and glutelin were extracted from Tartary buckwheat flour. Each fraction underwent sequential pepsin-trypsin hydrolysis to simulate gastrointestinal digestion. ACE inhibitory activity was measured for all hydrolysates. The most active fraction (albumin hydrolysate) was further purified using gel filtration chromatography and reversed-phase HPLC. Individual peptides were identified by nano-LC-MS/MS (nanoscale liquid chromatography-tandem mass spectrometry). Novel peptides were validated through computational molecular docking analysis.","limitations":"All testing was performed in vitro — ACE inhibition in a test tube does not guarantee blood pressure reduction in humans. The peptides need to survive absorption through the intestinal wall intact and reach the bloodstream at sufficient concentrations. Many food-derived ACE peptides lose activity after further metabolism. No animal or human blood pressure studies were conducted. The computational validation of novel peptides provides theoretical support but not experimental proof of activity. The specific sequences of the 14 novel peptides are not listed in the abstract."},{"rthcId":"RPEP-07107","title":"Synthesis of cell penetrating peptide sterol coupler and its liposome study on S-mRNA.","authors":"Li, Yuan; Ma, Wenlin; Su, Wen; Yan, Zhihong; Jia, Lin; Deng, Jie; Zhu, Ali; Xie, Yanbo; Li, Xinyi; Shao, Wanhui; Ma, Yuman; Che, Linze; Zhu, Tao; Wang, Haomeng; Li, Mingyuan; Yu, Peng","year":2023,"journal":"European journal of medicinal chemistry, 261, 115822","doi":"10.1016/j.ejmech.2023.115822","pmid":"37793325","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The novel chol-CGYKK molecule was successfully synthesized by connecting the peptide CGYKK to cholesterol via a disulfide linker. When incorporated into cationic liposomes carrying spike protein mRNA, the system maintained approximately 90% encapsulation rate after six months at 4°C — addressing a critical stability limitation of current LNP-mRNA systems.\n\nAmong four formulations tested with different excipient ratios, formulated sample 1 showed the highest spike protein expression. Its transfection efficiency reached 66.7% compared to the commercial transfection reagent Lipofectamine 2000.\n\nSafety evaluation showed no toxic effects from either the CGYKK peptide or the complete mRNA vaccine liposomes. In vivo studies demonstrated that the vaccine triggered an immune response, though it was not yet as strong as the LNP-based comparator group.","whyItMatters":"Current mRNA vaccines require ultra-cold storage (-20°C to -80°C), creating massive logistical challenges for global distribution. A delivery system that maintains 90% encapsulation at standard refrigerator temperature (4°C) for six months could dramatically simplify vaccine storage and distribution, particularly in developing countries lacking cold-chain infrastructure. The cell-penetrating peptide approach offers a fundamentally different design strategy from current LNP technology.","specificNumbers":"","methodology":"The CGYKK peptide was synthesized using solid-phase peptide synthesis and conjugated to cholesterol through a disulfide linker. Four liposome formulations with varying excipient proportions were prepared by freeze-drying cationic liposomes loaded with SARS-CoV-2 spike protein mRNA. Physical characterization was performed using transmission electron microscopy, atomic force microscopy, and scanning electron microscopy. Stability was assessed by measuring encapsulation rate over six months at 4°C. Biological activity was evaluated through cellular uptake studies, transfection efficiency compared to Lipofectamine 2000, protein expression measurement, safety/toxicity assessment, and in vivo immune response in animals.","limitations":"The in vivo immune response was weaker than the LNP comparator group, meaning this system is not yet competitive with existing technology in terms of efficacy. Transfection efficiency of 66.7% relative to Lipofectamine 2000 (a research-grade reagent, not a clinical product) is modest. The study does not provide detailed quantitative immune response data or compare to clinically approved LNP formulations. Long-term animal safety data beyond initial screening is not reported. The specific animal model and group sizes are not detailed in the abstract."},{"rthcId":"RPEP-07108","title":"Food-Derived Peptides: Beneficial CNS Effects and Cross-BBB Transmission Strategies.","authors":"Li, Zehui; Dang, Qiao; Wang, Peng; Zhao, Fanrui; Huang, Jianqin; Wang, Chongchong; Liu, Xingquan; Min, Weihong","year":2023,"journal":"Journal of agricultural and food chemistry, 71(51), 20453-20478","doi":"10.1021/acs.jafc.3c06518","pmid":"38085598","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07109","title":"Purification identification and function analysis of ACE inhibitory peptide from Ulva prolifera protein.","authors":"Li, Zhiyong; He, Yuan; He, Hongyan; Zhou, Weizhe; Li, Mengru; Lu, Aiming; Che, Tuanjie; Shen, Songdong","year":2023,"journal":"Food chemistry, 401, 134127","doi":"10.1016/j.foodchem.2022.134127","pmid":"36096005","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The peptide DIGGL was identified from Ulva prolifera protein hydrolysates with an IC50 value of 10.32 ± 0.96 μM for ACE inhibition, acting through a non-competitive mechanism primarily via three conventional hydrogen bonds with the enzyme.\n\nIn human umbilical vein endothelial cells, DIGGL activated endothelial nitric oxide synthase to increase NO production and reduced endothelin-1 secretion induced by angiotensin II. The peptide also promoted mouse splenocyte proliferation both alone and when co-incubated with immune stimulants (Con A or LPS), indicating immunomodulatory properties. Crucially, DIGGL remained active after simulated gastrointestinal digestion with pepsin and trypsin.","whyItMatters":"Finding natural food-derived peptides that can lower blood pressure is a growing area of research for developing functional foods and nutraceuticals. DIGGL is particularly promising because it comes from an abundant, edible seaweed, works at low concentrations, has multiple beneficial mechanisms (ACE inhibition plus nitric oxide boost), and survives digestion — a major hurdle for oral peptide bioactivity.","specificNumbers":"","methodology":"Researchers isolated protein from Ulva prolifera and hydrolyzed it using five commercial enzymes individually and in combination. The hydrolysate with the highest ACE inhibitory activity was purified through gel filtration, ultrafiltration, and HPLC-Q-TOF-MS. Computational ADMET screening and molecular docking were used to characterize the peptide-ACE interaction. Functional assays were performed on human endothelial cells and mouse splenocytes, and gastrointestinal stability was tested with simulated digestion.","limitations":"All experiments were conducted in vitro or in cell culture — there are no animal or human studies showing that DIGGL lowers blood pressure when consumed. The gastrointestinal stability test was simulated, not performed in a living system. Bioavailability (whether the peptide is absorbed into the bloodstream) was not assessed. The immunomodulatory effects on splenocytes need further investigation for relevance."},{"rthcId":"RPEP-07110","title":"Dual-Activity Fluoroquinolone-Transportan 10 Conjugates Offer Alternative Leukemia Therapy during Hematopoietic Cell Transplantation.","authors":"Lica, Jan Jakub; Heldt, Mateusz; Wieczór, Milosz; Chodnicki, Pawel; Ptaszyńska, Natalia; Maciejewska, Natalia; Łęgowska, Anna; Brankiewicz, Wioletta; Gucwa, Katarzyna; Stupak, Anna; Pradhan, Bhaskar; Gitlin-Domagalska, Agata; Dębowski, Dawid; Milewski, Sławomir; Bieniaszewska, Maria; Grabe, Grzegorz Jan; Hellmann, Andrzej; Rolka, Krzysztof","year":2023,"journal":"Molecular pharmacology, 105(1), 39-53","doi":"10.1124/molpharm.123.000735","pmid":"37977824","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07111","title":"The short-term cost-effectiveness of once-weekly semaglutide versus once-weekly dulaglutide for the treatment of type 2 diabetes mellitus in Colombian adults.","authors":"Liebisch-Rey, Hans; Suarez-Chacon, Andrea-Marcela; Fuentes, Yuli-V; Blanco, Jhosep; Kock, Joshua; Lechtig-Wassermann, Sharon; Bustos, Rosa Helena","year":2023,"journal":"F1000Research, 12, 914","doi":"10.12688/f1000research.128441.2","pmid":"38125558","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07112","title":"Impact of human telomerase reverse transcriptase peptide vaccine combined with androgen deprivation therapy and radiotherapy in de novo metastatic prostate cancer: Long-term clinical monitoring.","authors":"Lilleby, Wolfgang; Seierstad, Therese; Inderberg, Else Marit; Hole, Knut Håkon","year":2023,"journal":"International journal of cancer, 152(10), 2166-2173","doi":"10.1002/ijc.34448","pmid":"36715014","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"After a median follow-up of 62 months, nine of 22 patients were still alive. Six had no disease progression, two had castration-resistant disease on second-line therapy, and one had castration-refractory disease. Median time to PSA progression was 21 months, median overall survival was 62 months, and median prostate cancer-specific survival was 84 months.\n\nLack of immune response was an independent marker of prostate cancer death — patients who failed to mount an immune response to the vaccine had worse survival. Some patients showed unexpected late immune response surges without developing recurrence, suggesting ongoing immunological surveillance. These findings indicate clinical benefit of hTERT vaccination in a subgroup of patients.","whyItMatters":"Metastatic prostate cancer diagnosed at presentation carries a poor prognosis, with median survival typically around 4-5 years with standard therapy. The 62-month median overall survival and 84-month cancer-specific survival observed here are encouraging, particularly for a disease historically considered resistant to immunotherapy. The finding that immune response predicts survival provides a potential biomarker for identifying which patients benefit most from vaccination, moving toward personalized treatment strategies.","specificNumbers":"","methodology":"This was long-term clinical monitoring of a phase I/II study. Twenty-two men with high-grade (ISUP 4-5) de novo metastatic prostate cancer (lymph node and/or bone metastases) received the UV1 hTERT peptide vaccine combined with androgen deprivation therapy (ADT) and radiotherapy between January 2013 and July 2014. Immune responses were monitored before, during, and after vaccination, then every 6 months until PSA progression. MRI was performed at baseline, 6 months, 1 year, 2 years, and at progression.","limitations":"This is a small single-arm phase I/II study with only 22 patients and no control group, making it impossible to definitively attribute the survival results to the vaccine versus the combination of ADT and radiotherapy. The standard of care for metastatic prostate cancer has evolved since the trial began in 2013. The long follow-up period introduces survivor bias — patients alive at later time points may have had inherently less aggressive disease. External validation in a randomized controlled trial is needed."},{"rthcId":"RPEP-07113","title":"Development and application of novel peptide-formulated nanoparticles for treatment of atopic dermatitis.","authors":"Lim, Chaemin; Lee, Subin; Shin, Yuseon; Cho, Seongmin; Park, Chanho; Shin, Yungyeong; Song, Ee Chan; Kim, Wan Ki; Ham, Cheolmin; Kim, Sang Bum; Kwon, Yong-Su; Oh, Kyung Taek","year":2023,"journal":"Journal of materials chemistry. B, 11(42), 10131-10146","doi":"10.1039/d3tb01202f","pmid":"37830254","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07114","title":"No Evidence That Circulating GLP-1 or PYY Are Associated with Increased Satiety during Low Energy Diet-Induced Weight Loss: Modelling Biomarkers of Appetite.","authors":"Lim, Jia Jiet; Liu, Yutong; Lu, Louise W; Sequeira, Ivana R; Poppitt, Sally D","year":2023,"journal":"Nutrients, 15(10)","doi":"10.3390/nu15102399","pmid":"37242282","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07115","title":"Computational Modeling of Stapled Coiled-Coil Inhibitors Against Bcr-Abl: Toward a Treatment Strategy for CML.","authors":"Lima, Maria Carolina P; Hornsby, Braxten D; Lim, Carol S; Cheatham, Thomas E","year":2023,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2023.11.15.566894","pmid":"38014060","tags":[],"studyType":"computational","evidenceStrength":"preliminary","keyFinding":"The researchers used computational modeling to design next-generation stapled peptide inhibitors targeting Bcr-Abl, the fusion protein that causes chronic myeloid leukemia (CML). By incorporating hydrocarbon staples — chemical cross-links that lock the peptide into a stable helical shape — they aimed to overcome the conformational instability and protease vulnerability of their previous 81-amino-acid inhibitor construct.\n\nThe team modeled both single and double staple configurations across full-length and truncated peptide versions, with and without a cell-penetrating peptide (CPP) component. They identified lead candidates predicted to maintain strong binding to Bcr-Abl's coiled-coil oligomerization domain while being more stable and resistant to degradation than the unstapled version. These candidates are proposed for experimental validation.","whyItMatters":"Current CML treatments (tyrosine kinase inhibitors like imatinib) target Bcr-Abl's kinase domain, but resistance mutations remain a major problem. This peptide approach attacks a completely different target — the coiled-coil domain that Bcr-Abl needs to assemble and activate. If stapled peptide inhibitors can block this assembly, they could work even against kinase-inhibitor-resistant leukemia. This represents a fundamentally different therapeutic strategy for a common blood cancer.","specificNumbers":"81-amino-acid parent construct · Hydrocarbon staples at i, i+7 positions · 6 system variants modeled (full-length/truncated × no CPP/cyclic CPP/linear CPP) · Single and double staple candidates screened · Targets Bcr-CC oligomerization domain","methodology":"The researchers used computational molecular dynamics simulations to model and screen stapled peptide candidates. They evaluated binding energetics (how strongly the peptide binds its target), conformational stability (how well the peptide maintains its active shape), and the impact of different staple configurations. The modeling library included six system variants combining full-length versus truncated peptides with different cell-penetrating peptide configurations.","limitations":"This is entirely a computational study — no experimental synthesis or biological testing has been performed on the stapled candidates presented here. Computational predictions of binding affinity and stability don't always translate to actual biological activity. The bioRxiv preprint has not undergone peer review. Stapled peptides face general challenges with cellular uptake, tissue distribution, and manufacturing that aren't addressed by computational modeling alone."},{"rthcId":"RPEP-07116","title":"Therapeutic Prospection of Animal Venoms-Derived Antimicrobial Peptides against Infections by Multidrug-Resistant Acinetobacter baumannii: A Systematic Review of Pre-Clinical Studies.","authors":"Lima, William Gustavo; de Lima, Maria Elena","year":2023,"journal":"Toxins, 15(4)","doi":"10.3390/toxins15040268","pmid":"37104206","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The systematic review identified 8 preclinical studies testing 11 different animal venom-derived antimicrobial peptides against MDR Acinetobacter baumannii. Most AMPs originated from arthropod venoms (scorpions, spiders), and all were positively charged and rich in lysine residues.\n\nIn vivo testing showed these peptides reduced MDR-Ab-induced lethality and bacterial load across three infection models: invasive (bacteremia and pneumonia) and superficial (wound infections). Critically, the venom-derived AMPs demonstrated pleiotropic effects beyond direct bacterial killing — including pro-healing, anti-inflammatory, and antioxidant activities — that contribute to infection treatment and tissue recovery.","whyItMatters":"Acinetobacter baumannii is classified by the WHO as the number one critical-priority pathogen for which new antibiotics are urgently needed. Some strains are resistant to every available antibiotic. Venom-derived antimicrobial peptides offer several advantages: they kill bacteria through membrane disruption (making resistance development difficult), they work against MDR strains, and their additional anti-inflammatory and healing properties address the tissue damage that accompanies severe infections.","specificNumbers":"","methodology":"Systematic review following PRISMA guidelines. The authors searched for preclinical studies evaluating animal venom-derived antimicrobial peptides against MDR Acinetobacter baumannii infections in vivo. Eight studies meeting inclusion criteria were analyzed for AMP characteristics (charge, amino acid composition, venom source), antimicrobial activity, in vivo efficacy across different infection models, and additional biological activities.","limitations":"All 8 included studies are preclinical (animal models), with no human clinical data. The review found only 8 qualifying studies, reflecting the early stage of this research area. The specific infection models, peptide doses, and animal species varied across studies, making direct comparisons difficult. Manufacturing scalability and cost for venom-derived peptides are not addressed. Potential toxicity at therapeutic doses in humans requires investigation. The review focused specifically on MDR-Ab and may not reflect efficacy against other resistant pathogens."},{"rthcId":"RPEP-07117","title":"Analgesic efficacy of collagen peptide in knee osteoarthritis: a meta-analysis of randomized controlled trials.","authors":"Lin, Chun-Ru; Tsai, Sung Huang Laurent; Huang, Ko-Yen; Tsai, Po-An; Chou, Hsuan; Chang, Shu-Hao","year":2023,"journal":"Journal of orthopaedic surgery and research, 18(1), 694","doi":"10.1186/s13018-023-04182-w","pmid":"37717022","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07118","title":"Trends in use of sodium-glucose co-transporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) in Australia in the era of increased evidence of their cardiovascular benefits (2014-2022).","authors":"Lin, Jialing; Pearson, Sallie-Anne; Greenfield, Jerry R; Park, Kyeong Hye; Havard, Alys; Brieger, David; Day, Richard O; Falster, Michael O; de Oliveira Costa, Juliana","year":2023,"journal":"European journal of clinical pharmacology, 79(9), 1239-1248","doi":"10.1007/s00228-023-03539-8","pmid":"37449993","tags":[],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"GLP-1 receptor agonist use in Australia grew 11-fold between 2014 and 2022, reaching approximately 120,000 users by July 2022. SGLT2 inhibitor growth was even more dramatic at 216-fold, reaching 250,000 users.\n\nCritically, from 2022 onwards, about 1 in 5 new SGLT2i users didn't have type 2 diabetes — indicating expanding use for cardiovascular indications alone. Cardiologist-initiated prescriptions reached 10% of new SGLT2i starts by mid-2022. Among GLP-1 RA users with cardiovascular conditions, dulaglutide and semaglutide were the most commonly prescribed. Most new users of both drug classes had evidence of both diabetes and cardiovascular disease.","whyItMatters":"This study captures the real-time adoption of GLP-1 drugs as they transitioned from diabetes medications to cardiovascular drugs. The 11-fold growth in GLP-1 RA use and the emergence of non-diabetic prescribing reflect how cardiovascular outcome trial results (like SUSTAIN-6 and SELECT) transformed clinical practice. Australia's data shows a global trend: as evidence for peptide-based drugs' heart benefits accumulates, their prescribing base is expanding far beyond endocrinology into cardiology.","specificNumbers":"216-fold SGLT2i growth · 11-fold GLP-1 RA growth · ~250,000 SGLT2i users by July 2022 · ~120,000 GLP-1 RA users · 1 in 5 new SGLT2i users without T2D · 10% cardiologist initiation · 2014–2022 period","methodology":"Population-based study using national dispensing claims from a 10% random sample of Australians (January 2014 to July 2022). Researchers counted monthly prevalent and new users, assessed prescriber specialty, and used prior antidiabetic and cardiovascular medication use as proxies for diabetes and cardiovascular conditions.","limitations":"Australian data may not generalize to other healthcare systems with different drug access and reimbursement policies. Dispensing claims are a proxy — they show medications filled, not necessarily taken. Using prior medication claims as proxies for diabetes and cardiovascular disease may misclassify some patients. The 10% random sample may introduce sampling variability. Data ends July 2022, before the most dramatic semaglutide prescribing surge."},{"rthcId":"RPEP-07119","title":"An injectable and light curable hyaluronic acid composite gel with anti-biofilm, anti-inflammatory and pro-healing characteristics for accelerating infected wound healing.","authors":"Lin, Xiaolong; Fu, Tao; Lei, Yuqing; Xu, Jiajia; Wang, Sa; He, Fuming; Xie, Zhijian; Zhang, Ling","year":2023,"journal":"International journal of biological macromolecules, 253(Pt 5), 127190","doi":"10.1016/j.ijbiomac.2023.127190","pmid":"37802452","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07120","title":"Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes.","authors":"Lincoff, A Michael; Brown-Frandsen, Kirstine; Colhoun, Helen M; Deanfield, John; Emerson, Scott S; Esbjerg, Sille; Hardt-Lindberg, Søren; Hovingh, G Kees; Kahn, Steven E; Kushner, Robert F; Lingvay, Ildiko; Oral, Tugce K; Michelsen, Marie M; Plutzky, Jorge; Tornøe, Christoffer W; Ryan, Donna H","year":2023,"journal":"The New England journal of medicine, 389(24), 2221-2232","doi":"10.1056/NEJMoa2307563","pmid":"37952131","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07121","title":"Non-invasive in vivo imaging of porcine islet xenografts in a preclinical model with [68Ga]Ga-exendin-4.","authors":"Lindheimer, Felix; Lindner, Magdalena Julia; Oos, Rosel; Honarpisheh, Mohsen; Zhang, Yichen; Lei, Yutian; Wolf-van Buerck, Lelia; Gildehaus, Franz Josef; Lindner, Simon; Bartenstein, Peter; Kemter, Elisabeth; Wolf, Eckhard; Seissler, Jochen; Ziegler, Sibylle","year":2023,"journal":"Frontiers in nuclear medicine, 3, 1157480","doi":"10.3389/fnume.2023.1157480","pmid":"39355020","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07122","title":"Achievement of glycaemic targets with weight loss and without hypoglycaemia in type 2 diabetes with the once-weekly glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist tirzepatide: A post hoc analysis of the SURPASS-1 to -5 studies.","authors":"Lingvay, Ildiko; Cheng, Alice Yy; Levine, Joshua A; Gomez-Valderas, Elisa; Allen, Sheryl E; Ranta, Kari; Torcello-Gómez, Amelia; Thieu, Vivian T","year":2023,"journal":"Diabetes, obesity & metabolism, 25(4), 965-974","doi":"10.1111/dom.14943","pmid":"36514843","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07123","title":"Altered Expression of Antimicrobial Peptides in the Upper Gastrointestinal Tract of Patients with Diabetes Mellitus.","authors":"Linn, Oliver; Menges, Bernhard; Lammert, Frank; Weber, Susanne N; Krawczyk, Marcin","year":2023,"journal":"Nutrients, 15(3)","doi":"10.3390/nu15030754","pmid":"36771460","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"HBD-1 (human beta-defensin 1) mRNA expression was significantly decreased in the corpus mucosa of patients with type 2 diabetes compared to healthy controls. Both HBD-1 and HBD-3 were expressed in the stomach's corpus mucosa, with HBD-3 levels showing a negative correlation with vitamin D concentrations. Most participants had low vitamin D levels regardless of metabolic status.","whyItMatters":"The gut barrier is a critical line of defense against infection, and antimicrobial peptides are among its most important protectors. Showing that type 2 diabetes reduces these peptides helps explain why diabetic patients are more susceptible to gastrointestinal infections and complications. Understanding this link could eventually lead to targeted therapies to restore gut immune defenses in people with diabetes.","specificNumbers":"","methodology":"Researchers collected tissue samples from the upper gastrointestinal tract of 31 individuals — 10 with type 2 diabetes, 10 with insulin resistance, and 11 healthy controls. They measured mRNA expression of seven antimicrobial peptides (four beta-defensins, two alpha-defensins, and cathelicidin) using quantitative RT-PCR. They also measured serum vitamin D (25-hydroxyvitamin D3) levels and examined correlations with peptide expression.","limitations":"The study had a small sample size of just 31 participants, which limits statistical power and generalizability. It measured mRNA expression rather than actual peptide protein levels, so it's uncertain whether reduced gene expression translates directly to lower functional peptide concentrations. The study was also cross-sectional, meaning it cannot establish whether diabetes causes reduced peptide expression or if the relationship is merely correlational."},{"rthcId":"RPEP-07124","title":"Parahydrogen-induced polarization allows 2000-fold signal enhancement in biologically active derivatives of the peptide-based drug octreotide.","authors":"Lins, Jonas; Miloslavina, Yuliya A; Carrara, Stefania C; Rösler, Lorenz; Hofmann, Sarah; Herr, Kevin; Theiß, Franziska; Wienands, Laura; Avrutina, Olga; Kolmar, Harald; Buntkowsky, Gerd","year":2023,"journal":"Scientific reports, 13(1), 6388","doi":"10.1038/s41598-023-33577-2","pmid":"37076553","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07125","title":"KIT A502_Y503 duplication mutation serves as a potential and universal target for neoantigen peptide in Chinese GIST patients.","authors":"Liu, Fangcen; Wang, Qin; Li, Yishan; Li, Lin; Shi, Jiaochun; Fan, Xiangshan; Pan, Qiuyue; Li, Rutian","year":2023,"journal":"Journal of gastroenterology and hepatology, 38(7), 1123-1130","doi":"10.1111/jgh.16165","pmid":"36879550","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07126","title":"Peptide Receptor Radionuclide Therapy in Patients With Advanced Progressive Medullary Thyroid Cancer: Efficacy, Safety, and Survival Predictors.","authors":"Liu, Qingxing; Kulkarni, Harshad R; Zhao, Tianzhi; Schuchardt, Christiane; Chen, Xiaoyuan; Zhu, Zhaohui; Zhang, Jingjing; Baum, Richard P","year":2023,"journal":"Clinical nuclear medicine, 48(3), 221-227","doi":"10.1097/RLU.0000000000004539","pmid":"36723881","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07127","title":"Microbiota-derived short-chain fatty acids and modulation of host-derived peptides formation: Focused on host defense peptides.","authors":"Liu, Tianzhou; Sun, Zhen; Yang, Zecheng; Qiao, Xiaofang","year":2023,"journal":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 162, 114586","doi":"10.1016/j.biopha.2023.114586","pmid":"36989711","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07128","title":"PEGylated exenatide injection (PB-119) improves beta-cell function and insulin resistance in treatment-naïve type 2 diabetes mellitus patients.","authors":"Liu, Xu; Song, Ling; Zhang, Yuanhui; Li, Haiyan; Cui, Cheng; Liu, Dongyang","year":2023,"journal":"Frontiers in pharmacology, 14, 1088670","doi":"10.3389/fphar.2023.1088670","pmid":"37781697","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07129","title":"Featured Prebiotic Agent: The Roles and Mechanisms of Direct and Indirect Prebiotic Activities of Lactoferrin and Its Application in Disease Control.","authors":"Liu, Zhen-Shu; Chen, Po-Wen","year":2023,"journal":"Nutrients, 15(12)","doi":"10.3390/nu15122759","pmid":"37375663","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07130","title":"Improve BBB Penetration and Cytotoxicity of Palbociclib in U87-MG Glioblastoma Cells Delivered by Dual Peptide Functionalized Nanoparticles.","authors":"Lo, Yu-Chen; Lin, Wen-Jen","year":2023,"journal":"Pharmaceutics, 15(10)","doi":"10.3390/pharmaceutics15102429","pmid":"37896189","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"PLGA-PEG nanoparticles were functionalized with T7 targeting peptide and R9 cell-penetrating peptide, yielding particles of 168-186 nm with high drug loading efficiency (>80%). In a transwell BBB model using bEnd.3 cells, the penetration efficiency ranked: T7/R9 dual-peptide NPs > T7-peptide NPs > peptide-free NPs > free palbociclib.\n\nThe dual-peptide modified nanoparticles enhanced U87-MG glioblastoma cell apoptosis by 2.3 to 6.5-fold relative to free palbociclib, with the dual-peptide formulation being the most effective. The sequential mechanism — BBB penetration facilitated by T7/R9, followed by targeting to glioma cells — demonstrated effective cytotoxicity and promoted cell death.","whyItMatters":"Glioblastoma is nearly always fatal partly because the blood-brain barrier prevents most drugs from reaching the tumor. Palbociclib is already proven effective against glioma cells in the lab but can't get past the BBB in sufficient quantities. This dual-peptide nanoparticle approach solves both problems — crossing the BBB and enhancing drug uptake into cancer cells — using two peptides with complementary functions.","specificNumbers":"","methodology":"PLGA-PEG nanoparticles were prepared and functionalized with T7 peptide, R9 peptide, or both. Palbociclib was loaded and encapsulation efficiency measured. BBB penetration was assessed using a bEnd.3 cell transwell model. Cytotoxicity and apoptosis were evaluated in U87-MG glioblastoma cells. Cellular uptake was compared across formulations.","limitations":"This was entirely an in vitro study using cell-based BBB models, which are simplified representations of the actual blood-brain barrier. No animal studies were conducted to validate BBB crossing in vivo. The bEnd.3 transwell model lacks important BBB features like astrocyte interactions and blood flow. Long-term stability, pharmacokinetics, and biodistribution of the nanoparticles are unknown. Off-target effects of the cell-penetrating R9 peptide on healthy brain tissue were not assessed."},{"rthcId":"RPEP-07131","title":"Venom Peptides, Polyphenols and Alkaloids: Are They the Next Antidiabetics That Will Preserve β-Cell Mass and Function in Type 2 Diabetes?","authors":"Lodato, Michele; Plaisance, Valérie; Pawlowski, Valérie; Kwapich, Maxime; Barras, Alexandre; Buissart, Emeline; Dalle, Stéphane; Szunerits, Sabine; Vicogne, Jérôme; Boukherroub, Rabah; Abderrahmani, Amar","year":2023,"journal":"Cells, 12(6)","doi":"10.3390/cells12060940","pmid":"36980281","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07132","title":"Semaglutide 2·4 mg once weekly in patients with non-alcoholic steatohepatitis-related cirrhosis: a randomised, placebo-controlled phase 2 trial.","authors":"Loomba, Rohit; Abdelmalek, Manal F; Armstrong, Matthew J; Jara, Maximilian; Kjær, Mette Skalshøi; Krarup, Niels; Lawitz, Eric; Ratziu, Vlad; Sanyal, Arun J; Schattenberg, Jörn M; Newsome, Philip N","year":2023,"journal":"The lancet. Gastroenterology & hepatology, 8(6), 511-522","doi":"10.1016/S2468-1253(23)00068-7","pmid":"36934740","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07133","title":"Peptide Stapling Applied to Antimicrobial Peptides.","authors":"Lourenço, Ana Laura Pereira; Rios, Thuanny Borba; da Silva, Állan Pires; Franco, Octávio Luiz; Ramada, Marcelo Henrique Soller","year":2023,"journal":"Antibiotics (Basel, Switzerland), 12(9)","doi":"10.3390/antibiotics12091400","pmid":"37760697","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07134","title":"GHRH agonist MR-409 protects β-cells from streptozotocin-induced diabetes.","authors":"Louzada, Ruy A; Blandino-Rosano, Manuel; Flores, Sebastian; Lubaczeuski, Camila; Cui, Tengjiao; Sha, Wei; Cai, Renzhi; Schally, Andrew V; Bernal-Mizrachi, Ernesto","year":2023,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 120(25), e2209810120","doi":"10.1073/pnas.2209810120","pmid":"37307472","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"MR-409 activated the cAMP/PKA/CREB/IRS2 signaling axis in beta cells, inducing insulin receptor substrate 2 (IRS2) — a master regulator of beta cell survival and growth — in a PKA-dependent manner. This pathway activation was associated with decreased beta cell death and improved insulin secretion in both mouse and human islets exposed to pro-inflammatory cytokines.\n\nIn the streptozotocin-induced type 1 diabetes mouse model, MR-409-treated mice showed better glucose homeostasis, higher circulating insulin levels, and preservation of beta cell mass compared to untreated animals. Increased IRS2 expression was confirmed in vivo, providing mechanistic consistency with the in vitro findings.","whyItMatters":"Type 1 diabetes currently has no cure — patients require lifelong insulin injections because their beta cells have been destroyed by autoimmune attack. A peptide that can protect surviving beta cells from inflammatory destruction could slow or prevent disease progression, particularly if administered early. This is especially significant because it works on human islets, not just mouse cells.","specificNumbers":"","methodology":"The study used both in vitro and in vivo approaches. In vitro: insulinoma cell lines plus rodent and human pancreatic islets were treated with MR-409 and exposed to pro-inflammatory cytokines. Cell death, insulin secretion, and signaling pathways were measured. In vivo: a type 1 diabetes model was induced in mice using low-dose streptozotocin. MR-409-treated mice were compared to controls for glucose homeostasis, insulin levels, and beta cell mass preservation.","limitations":"This is a preclinical study. The streptozotocin mouse model mimics aspects of type 1 diabetes but does not fully replicate the human autoimmune process. The study focused on beta cell protection rather than reversing established disease. Long-term effects and optimal dosing in vivo were not fully characterized. Human clinical trials would be needed to validate these findings."},{"rthcId":"RPEP-07135","title":"Peptide Receptor Radionuclide Therapy Performed Shortly After Administration of Long-Acting Octreotide.","authors":"Low, Han Chung; Tay, Young Soon; Ong, Simon Yew Kuang; Tham, Wei Ying; Yan, Sean Xuexian","year":2023,"journal":"Clinical nuclear medicine, 48(12), 1086-1088","doi":"10.1097/RLU.0000000000004906","pmid":"37844418","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A 68-year-old man with metastatic small bowel neuroendocrine tumor received his fourth cycle of 177Lu-DOTATATE PRRT only 48 hours after his last dose of octreotide LAR, compared to the approximately 4-week interval used for his first 3 cycles. Tumoral uptake was not reduced at all compared to previous cycles, suggesting octreotide LAR does not meaningfully compete with 177Lu-DOTATATE for somatostatin receptor binding in this timeframe.","whyItMatters":"If somatostatin analogs like octreotide don't need to be stopped before PRRT, patients could continue receiving the symptom-controlling benefits of octreotide right up to therapy. The current washout period can cause symptom flare-ups and scheduling difficulties, so eliminating it would improve patient quality of life and treatment logistics.","specificNumbers":"","methodology":"This is a single-patient case report comparing tumoral uptake of 177Lu-DOTATATE across 4 PRRT cycles in the same patient. The first 3 cycles followed standard protocol (~4 weeks after octreotide LAR), while the fourth was administered 48 hours after octreotide due to a scheduling error. Uptake was assessed using standard nuclear medicine imaging.","limitations":"This is a single case report — the lowest level of clinical evidence. The finding in one patient cannot be generalized without larger studies. There was no formal pharmacokinetic analysis, and uptake assessment was qualitative rather than rigorously quantitative."},{"rthcId":"RPEP-07136","title":"Neuropeptide Y receptor Y2 (npy2r) deficiency reduces anxiety and increases food intake in Japanese medaka (Oryzias latipes).","authors":"Lu, Ke; Jia, Xiaodan; Wu, Jiaqi; Wang, Qiuling; Liang, Xu-Fang","year":2023,"journal":"Frontiers in cell and developmental biology, 11, 1273006","doi":"10.3389/fcell.2023.1273006","pmid":"38020893","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07137","title":"Double layer spherical nanoparticles with hyaluronic acid coating to enhance oral delivery of exenatide in T2DM rats.","authors":"Lu, Yiying; Wu, Linjie; Lin, Mengting; Bao, Xiaoyan; Zhong, Haiqing; Ke, Peng; Dai, Qi; Yang, Qiyao; Tang, Xinjiang; Xu, WenHong; Xu, DongHang; Han, Min","year":2023,"journal":"European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 191, 205-218","doi":"10.1016/j.ejpb.2023.09.003","pmid":"37683898","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07138","title":"Boosting systemic absorption of peptides with a bioinspired buccal-stretching patch.","authors":"Luo, Zhi; Klein Cerrejon, David; Römer, Simon; Zoratto, Nicole; Leroux, Jean-Christophe","year":2023,"journal":"Science translational medicine, 15(715), eabq1887","doi":"10.1126/scitranslmed.abq1887","pmid":"37756378","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07139","title":"A small-molecule degrader of TET3 as treatment for anorexia nervosa in an animal model.","authors":"Lv, Haining; Catarino, Jonatas; Li, Da; Liu, Beibei; Gao, Xiao-Bing; Horvath, Tamas L; Huang, Yingqun","year":2023,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 120(16), e2300015120","doi":"10.1073/pnas.2300015120","pmid":"37036983","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Bobcat339 induced TET3 protein degradation specifically in hypothalamic AgRP neurons, leading to:\n\n- **Increased neuropeptide expression**: Upregulation of AgRP (agouti-related peptide), NPY (neuropeptide Y), and VGAT (vesicular GABA transporter) — all drivers of feeding behavior.\n- **Behavioral rescue in ABA model**: Increased food intake, decreased compulsive running wheel activity, and reduced lethality in the activity-based anorexia mouse model.\n- **Conserved mechanism**: Bobcat339 stimulated AgRP, NPY, and VGAT expression in a TET3-dependent manner in both mouse and human neuronal cells, suggesting cross-species relevance.\n- **Anxiolytic effects**: The treatment also reduced anxiety/depressive-like behaviors.","whyItMatters":"Anorexia nervosa kills more people than any other psychiatric disorder, and there are currently no FDA-approved drugs for it. This study identifies a druggable molecular target (TET3) that controls the brain's most powerful hunger-driving neuropeptides. By activating the AgRP/NPY system — which directly drives feeding — Bobcat339 addresses the core biological dysfunction in anorexia rather than just managing symptoms.","specificNumbers":"","methodology":"The study used the well-established activity-based anorexia (ABA) mouse model, which combines food restriction with voluntary running wheel access — mice develop paradoxical hyperactivity and self-starvation mimicking human anorexia nervosa. Bobcat339 was administered to ABA mice, and outcomes included food intake, running wheel activity, body weight, and survival. Mechanistic studies used immunohistochemistry, gene expression analysis, and both mouse and human neuronal cell cultures to confirm TET3 degradation and neuropeptide upregulation.","limitations":"The activity-based anorexia model captures some but not all aspects of human anorexia nervosa (a complex psychiatric condition with psychological, social, and genetic components). Bobcat339's selectivity for TET3 versus other TET family members (TET1, TET2) was not fully characterized, raising potential off-target concerns. Long-term safety of TET3 inhibition is unknown, as TET enzymes play broad roles in gene regulation. No human studies have been conducted."},{"rthcId":"RPEP-07140","title":"Active Ingredients of Schisandra chinensis Fruit Oil and their Effect on Propionibacterium acnes-Induced Inflammation in HaCaT Cells.","authors":"Lv, Pingping; Zhang, Huirong; Tai, Meiling; Che, Biao; Yu, Dan; Zhang, Ying; Li, Haodong; Meng, Xianyao; Guo, Miaomiao; Li, Li","year":2023,"journal":"Frontiers in bioscience (Landmark edition), 28(8), 177","doi":"10.31083/j.fbl2808177","pmid":"37664918","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07141","title":"Integrative analysis highlights molecular and immune responses of tick Amblyomma americanum to Escherichia coli challenge.","authors":"Lyu, Bo; Li, Jingjing; Niemeyer, Brigid; Anderson, Deborah M; Beerntsen, Brenda; Song, Qisheng","year":2023,"journal":"Frontiers in cellular and infection microbiology, 13, 1236785","doi":"10.3389/fcimb.2023.1236785","pmid":"37583446","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07142","title":"High-Throughput Screening for Epigenetic Compounds That Induce Human β-Defensin 1 Synthesis.","authors":"Lyu, Wentao; Deng, Zhuo; Zhang, Guolong","year":2023,"journal":"Antibiotics (Basel, Switzerland), 12(2)","doi":"10.3390/antibiotics12020186","pmid":"36830097","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07143","title":"Modulating Secondary Structure Motifs Through Photo-Labile Peptide Staples.","authors":"Lāce, Ilze; Bazzi, Sophia; Uranga, Jon; Schirmacher, Anastasiya; Diederichsen, Ulf; Mata, Ricardo A; Simeth, Nadja A","year":2023,"journal":"Chembiochem : a European journal of chemical biology, 24(16), e202300270","doi":"10.1002/cbic.202300270","pmid":"37216330","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07144","title":"Revealing the Sequence Characteristics and Molecular Mechanisms of ACE Inhibitory Peptides by Comprehensive Characterization of 160,000 Tetrapeptides.","authors":"Ma, Mingzhe; Feng, Yinghui; Miao, Yulu; Shen, Qiang; Tang, Shuting; Dong, Juan; Zhang, John Z H; Zhang, Lujia","year":2023,"journal":"Foods (Basel, Switzerland), 12(8)","doi":"10.3390/foods12081573","pmid":"37107368","tags":["bioactive-peptides","cardiovascular"],"studyType":"computational","evidenceStrength":"preliminary","keyFinding":"By computationally screening 160,000 possible four-amino-acid peptides against ACE (the enzyme targeted by blood pressure drugs like lisinopril), researchers identified the amino acid characteristics that make a peptide a strong ACE inhibitor. Tryptophan (Trp) was the most important amino acid, followed by tyrosine, phenylalanine, histidine, and arginine.\n\nThe top-performing tetrapeptides (WWNW, WRQF, WFRV, etc.) had IC50 values between 19.98 and 36.76 μM — potent for food-derived peptides. The binding was driven by salt bridges, π-π stacking, π-cation interactions, and hydrogen bonds. In a striking proof of concept, inserting eight tryptophan residues into rabbit skeletal muscle protein (which naturally has no tryptophan) gave it over 90% ACE inhibition, suggesting that tryptophan-rich meat proteins could have blood pressure benefits.","whyItMatters":"ACE inhibitor drugs are among the most prescribed medications worldwide for hypertension. Food-derived ACE-inhibitory peptides offer a natural, lower-side-effect alternative, but finding effective sequences has been largely trial and error. This systematic computational approach screens the entire tetrapeptide space at once, revealing clear design rules (tryptophan is king) that could accelerate discovery of functional food peptides for blood pressure management.","specificNumbers":"160,000 tetrapeptides screened · Top IC50: 19.98 ± 8.19 μM · Tryptophan = most important amino acid · >90% ACE inhibition with Trp-enriched protein · 6 top peptides identified","methodology":"Computational molecular docking of all 160,000 possible tetrapeptide combinations against the ACE enzyme structure. Top candidates were validated with in vitro ACE inhibition assays (IC50 measurements). Molecular interaction analysis identified the chemical bonds driving inhibition. A proof-of-concept experiment introduced tryptophan residues into a naturally tryptophan-free protein to test the predictive power of the findings.","limitations":"Molecular docking is a computational prediction — actual biological activity can differ. The IC50 values are from in vitro enzyme assays, not from human blood pressure studies. Bioavailability (whether these peptides survive digestion and reach the bloodstream intact) was not tested. The 90% ACE inhibition from engineered protein was in vitro, not in an animal or human model."},{"rthcId":"RPEP-07145","title":"Challenging Clinical Perspectives in Type 2 Diabetes with Tirzepatide, a First-in-Class Twincretin.","authors":"MacIsaac, Richard J; Deed, Gary; D'Emden, Michael; Ekinci, Elif I; Hocking, Samantha; Sumithran, Priya; Rasalam, Roy","year":2023,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 14(12), 1997-2014","doi":"10.1007/s13300-023-01475-5","pmid":"37824027","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07146","title":"Deciphering specificity and cross-reactivity in tachykinin NK1 and NK2 receptors.","authors":"Madsen, Jesper J; Petersen, Jacob E; Christensen, Dan P; Hansen, Jakob B; Schwartz, Thue W; Frimurer, Thomas M; Olsen, Ole H","year":2023,"journal":"The Journal of biological chemistry, 299(12), 105438","doi":"10.1016/j.jbc.2023.105438","pmid":"37944618","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The specificity and cross-reactivity of substance P (SP) and neurokinin A (NKA) at NK1R and NK2R is determined by interactions between the amino acids preceding the shared FxGLM consensus motif and two receptor regions: the β-hairpin of extracellular loop 2 (ECL2) and a segment of the N-terminus leading into transmembrane helix 1. Positively charged residues R177 (NK1R) and K180 (NK2R) in ECL2 play vital roles in these interactions.\n\nThe N-terminal positions 1–3 of the peptide ligands were entirely dispensable for receptor activation, meaning the selectivity determinants reside in the central peptide region. Mutated and chimeric receptor constructs, along with modified ligands, cleanly swapped specificity between NK1R and NK2R as predicted by the structural model, validating the structure-activity hypotheses.","whyItMatters":"NK1 and NK2 receptors are drug targets for pain, inflammation, nausea, and respiratory diseases. NK1 antagonists (like aprepitant for chemotherapy-induced nausea) are already approved. Understanding exactly why substance P prefers NK1 while neurokinin A prefers NK2 — and how to eliminate cross-reactivity — enables the design of more selective peptide agonists and antagonists with fewer off-target effects.","specificNumbers":"","methodology":"The researchers used a combination of molecular modeling, receptor mutagenesis, and chimeric receptor/ligand constructs to map the interactions underlying tachykinin receptor specificity. They modeled ligand-bound receptor complexes, identified key contact residues, and validated predictions by swapping residues between NK1R and NK2R to test whether peptide preferences changed accordingly. Functional assays confirmed the activation profiles of the engineered constructs.","limitations":"The study is primarily computational and in vitro, relying on molecular modeling and cell-based assays rather than in vivo experiments. While the chimeric construct approach provides elegant proof-of-concept, the simplified receptor models may not capture all the complexities of receptor-ligand interactions in living tissues, where factors like membrane composition, receptor oligomerization, and accessory proteins can influence binding. The findings need validation in physiological settings."},{"rthcId":"RPEP-07147","title":"Gut microbiota modulation in patients with non-alcoholic fatty liver disease: Effects of current treatments and future strategies.","authors":"Maestri, Marta; Santopaolo, Francesco; Pompili, Maurizio; Gasbarrini, Antonio; Ponziani, Francesca Romana","year":2023,"journal":"Frontiers in nutrition, 10, 1110536","doi":"10.3389/fnut.2023.1110536","pmid":"36875849","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07148","title":"Management of Functional Pancreatic Neuroendocrine Neoplasms.","authors":"Magi, Ludovica; Marasco, Matteo; Rinzivillo, Maria; Faggiano, Antongiulio; Panzuto, Francesco","year":2023,"journal":"Current treatment options in oncology, 24(7), 725-741","doi":"10.1007/s11864-023-01085-0","pmid":"37103745","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07149","title":"Topical N-phosphonacetyl-l-aspartate is a dual action candidate for treating non-melanoma skin cancer.","authors":"Mahen, Kala K; Markley, Lilian; Bogart, Jolie; Klatka, Hope; Krishna, Vijay; Maytin, Edward V; Stark, George R; McDonald, Christine","year":2023,"journal":"Experimental dermatology, 32(9), 1485-1497","doi":"10.1111/exd.14853","pmid":"37309615","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07150","title":"Intrinsically Disordered Ku Protein-Derived Cell-Penetrating Peptides.","authors":"Maity, Biswanath; Moorthy, Hariharan; Govindaraju, Thimmaiah","year":2023,"journal":"ACS bio & med chem Au, 3(6), 471-479","doi":"10.1021/acsbiomedchemau.3c00032","pmid":"38144254","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Ku-P4, derived from the intrinsically disordered tail extensions of Ku proteins, showed high cell internalization efficacy and biocompatibility. Biophysical studies identified the proline residue as crucial for maintaining the disordered state that enables both biocompatibility and cell penetration. Ku-P4 effectively condensed DNA into positively charged polyplexes that penetrated cell membranes and delivered plasmid DNA intracellularly. The peptides represent a new class of CPPs based on intrinsically disordered protein regions.","whyItMatters":"Cell-penetrating peptides are essential tools for delivering drugs and gene therapies that can't cross cell membranes on their own. Most current CPPs are based on viral or toxin-derived sequences, which can have toxicity issues. Deriving CPPs from a human DNA-repair protein (Ku) represents a novel, potentially safer approach. The finding that structural disorder is key to function provides important design principles for next-generation delivery peptides.","specificNumbers":"","methodology":"Researchers designed peptides derived from the flexible, disordered tail extensions of Ku DNA-binding proteins. Multiple peptide variants were synthesized and tested for cell penetration efficiency, biocompatibility, and structural properties. Biophysical studies characterized the peptides' structural disorder and the role of proline residues. DNA binding and condensation were assessed to form polyplexes. Cell membrane penetration and intracellular DNA delivery were evaluated in cell culture.","limitations":"All experiments were conducted in cell culture — no in vivo delivery data were generated. The efficiency of DNA delivery relative to established transfection methods was not quantitatively compared. The mechanism of cell penetration (endocytosis vs. direct translocation) was not fully characterized. Stability in biological fluids and potential for immune responses were not assessed. The study used plasmid DNA but did not test delivery of other cargo types (proteins, small molecules, siRNA)."},{"rthcId":"RPEP-07151","title":"Pharmacotherapy for obesity: recent evolution and implications for cardiovascular risk reduction.","authors":"Maki, Kevin C; Kirkpatrick, Carol F; Allison, David B; Gadde, Kishore M","year":2023,"journal":"Expert review of endocrinology & metabolism, 18(4), 307-319","doi":"10.1080/17446651.2023.2209176","pmid":"37199542","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review compares three tiers of obesity treatment:\n\n1. Lifestyle interventions and older pharmacotherapies: associated with less than 12% body weight reduction and no clear evidence of reduced major adverse cardiovascular events (MACE)\n\n2. Bariatric surgery: achieves 20-30% body weight reduction and is associated with markedly lower subsequent MACE risk\n\n3. Newer peptide-based pharmacotherapies (semaglutide, tirzepatide): show greater weight loss efficacy compared to older drugs and are being evaluated in cardiovascular outcomes trials\n\nThe review notes that obesity drug prescribing remains relatively rare, partly due to concerns about long-term safety, provider bias, and lack of clear MACE reduction evidence. However, if ongoing trials demonstrate cardiovascular benefits for the newer agents, this is likely to drive expanded use.","whyItMatters":"Obesity affects over 40% of U.S. adults and is a major driver of heart disease, the leading cause of death. If peptide-based weight loss drugs can demonstrate not just weight reduction but actual prevention of heart attacks and strokes, it would represent a paradigm shift in how obesity is treated — moving it from a cosmetic concern to a directly treatable cardiovascular risk factor, potentially saving hundreds of thousands of lives.","specificNumbers":"","methodology":"This is a narrative review article that surveys the evidence on weight loss therapies and their effects on major adverse cardiovascular event (MACE) risk. The authors compare lifestyle interventions, older anti-obesity pharmacotherapies, bariatric surgery, and newer peptide-based medications (semaglutide, tirzepatide) in terms of weight loss efficacy and cardiovascular outcomes.","limitations":"As a narrative review, this does not present original data or systematic methodology. It was published before the results of key cardiovascular outcomes trials (including SELECT for semaglutide), so some of its open questions have since been answered. The review focuses primarily on U.S. obesity prevalence and treatment patterns. Cost, insurance coverage, and drug supply issues — major barriers to GLP-1 agonist adoption — are not extensively discussed."},{"rthcId":"RPEP-07152","title":"Diversity of Antimicrobial Peptides in Silkworm.","authors":"Makwana, Pooja; Rahul, Kamidi; Ito, Katsuhiko; Subhadra, Bindu","year":2023,"journal":"Life (Basel, Switzerland), 13(5)","doi":"10.3390/life13051161","pmid":"37240807","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Seven classes of antimicrobial peptides have been identified from silkworms: attacins, cecropins, defensins, enbocins, gloverins, lebocins, and moricins. Each class has distinct structural features and antimicrobial mechanisms.\n\nThese peptides collectively exhibit activity against bacteria, fungi, and viruses. A key advantage noted is that microorganisms cannot easily develop resistance to AMPs due to their membrane-targeting mechanisms. The review describes the immune signaling pathways (including Toll and Imd pathways) that regulate AMP production in silkworms in response to pathogen invasion.","whyItMatters":"The antibiotic pipeline is drying up while resistance grows. Insect-derived AMPs represent an underexplored reservoir of potential therapeutics. Silkworms are particularly attractive because they are already mass-produced for silk, making peptide sourcing potentially scalable. The seven distinct peptide classes offer multiple starting points for drug development.","specificNumbers":"","methodology":"This is a narrative review compiling published research on antimicrobial peptides isolated from silkworms (Bombyx mori). The review covers immune responses to pathogens, AMP isolation methods, structural classification, and antimicrobial activity data against various microorganisms.","limitations":"This is a review article without new experimental data. Many of the cited AMP activities were demonstrated in vitro, and clinical translation remains distant. The peptides' stability, toxicity to human cells, and pharmacokinetic properties are largely unstudied. The review does not provide quantitative comparisons of potency across the seven AMP classes."},{"rthcId":"RPEP-07153","title":"C. difficile intoxicates neurons and pericytes to drive neurogenic inflammation.","authors":"Manion, John; Musser, Melissa A; Kuziel, Gavin A; Liu, Min; Shepherd, Amy; Wang, Siyu; Lee, Pyung-Gang; Zhao, Leo; Zhang, Jie; Marreddy, Ravi K R; Goldsmith, Jeffrey D; Yuan, Ke; Hurdle, Julian G; Gerhard, Ralf; Jin, Rongsheng; Rakoff-Nahoum, Seth; Rao, Meenakshi; Dong, Min","year":2023,"journal":"Nature, 622(7983), 611-618","doi":"10.1038/s41586-023-06607-2","pmid":"37699522","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"TcdB (toxin B) from C. difficile targets gut-innervating afferent neurons via Frizzled receptors (FZD1/2/7) and pericytes via CSPG4, stimulating secretion of substance P (SP) and CGRP from neurons and proinflammatory cytokines from pericytes. This drives neurogenic inflammation.\n\nKey proof: selectively activating the TcdB enzymatic domain in sensory neurons alone was sufficient to cause major CDI-like colonic pathology. Conversely, mice lacking SP, CGRP, or the NK1R receptor showed reduced pathology. Blocking SP or CGRP signaling reduced both tissue damage and C. difficile bacterial burden in mice infected with standard and hypervirulent strains.","whyItMatters":"C. difficile infections kill thousands of people annually and are increasingly difficult to treat due to antibiotic resistance and high recurrence rates. Current treatments target the bacteria directly, but this study reveals that much of the damage comes from the body's own neuropeptide-driven inflammatory response. Blocking substance P or CGRP — for which drugs already exist (NK1R antagonists, CGRP antibodies) — could offer a completely new treatment strategy that targets the host response rather than the bacteria.","specificNumbers":"","methodology":"The researchers used a combination of in vitro cell biology, receptor identification, and in vivo mouse models. They identified TcdB receptors on neurons and pericytes, measured neuropeptide secretion, and used a novel 'toxogenetics' approach — delivering the TcdB enzymatic domain specifically to sensory neurons via a modified diphtheria toxin — to prove neurogenic inflammation is sufficient for CDI pathology. Knockout mice lacking SP, CGRP, or NK1R were used to confirm the role of these peptides. Pharmacological blockade of neuropeptide signaling was tested in C. difficile infection models including hypervirulent strains.","limitations":"This is a mouse study, and the neurogenic inflammation mechanisms may not be identical in humans. The specific drug doses and administration routes for neuropeptide blockade in CDI patients would need to be established through clinical trials. The study demonstrates proof of concept but does not establish optimal treatment protocols. Whether neuropeptide blockade would be sufficient as monotherapy or needs to be combined with antibiotics is not addressed."},{"rthcId":"RPEP-07154","title":"Cardiovascular prevention with glucose-lowering drugs in type 2 diabetes: An evidence-based approach to the categories of primary and secondary prevention.","authors":"Mannucci, Edoardo; Silverii, Giovanni Antonio","year":2023,"journal":"Diabetes, obesity & metabolism, 25(12), 3435-3443","doi":"10.1111/dom.15226","pmid":"37529868","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07155","title":"Is It Still Relevant to Discover New ACE Inhibitors from Natural Products? YES, but Only with Comprehensive Approaches to Address the Patients' Real Problems: Chronic Dry Cough and Angioedema.","authors":"Manoharan, Sivananthan","year":2023,"journal":"Molecules (Basel, Switzerland), 28(11)","doi":"10.3390/molecules28114532","pmid":"37299008","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies a key insight: current ACE inhibitors block both the C-domain and N-domain of ACE, which causes bradykinin to accumulate and trigger dry cough and angioedema. However, blood pressure regulation primarily involves the C-domain. Natural peptides — especially those with tryptophan at the C-terminal — could be designed or selected to inhibit only the C-domain, theoretically controlling blood pressure without the side effects.\n\nThe proposed discovery pipeline involves: isolating peptides from natural products, testing their stability against gastrointestinal enzymes (for oral delivery), selecting those with favorable amino acid compositions, and using molecular docking and dynamics to confirm C-domain-specific inhibition.","whyItMatters":"ACE inhibitors are among the most prescribed cardiovascular medications worldwide, and recent evidence suggests they may be preferable to ARBs (the alternative) for certain patient populations, including those with both hypertension and diabetes. But the cough and angioedema side effects drive many patients to switch medications. If domain-specific ACE inhibitory peptides from food sources could be developed, they could provide blood pressure control without these side effects — potentially as functional foods or as pharmaceutical candidates.","specificNumbers":"","methodology":"This is a review/perspective article that synthesizes current knowledge about ACE enzyme structure, the mechanism of ACE inhibitor side effects, and the potential of natural product-derived peptides. The author proposes a computational and experimental framework for discovering domain-specific ACE inhibitory peptides, incorporating molecular docking, dynamics simulations, and gastrointestinal stability testing.","limitations":"This is a perspective article that proposes a strategy but does not present experimental validation. The assumption that C-domain-specific peptide inhibitors would avoid bradykinin accumulation, while mechanistically reasonable, has not been clinically demonstrated. Natural peptides may face challenges with bioavailability, stability, and potency compared to established pharmaceutical ACE inhibitors. The practical feasibility of the proposed discovery pipeline is not demonstrated."},{"rthcId":"RPEP-07156","title":"Neurohumoral Activation in Heart Failure.","authors":"Manolis, Antonis A; Manolis, Theodora A; Manolis, Antonis S","year":2023,"journal":"International journal of molecular sciences, 24(20)","doi":"10.3390/ijms242015472","pmid":"37895150","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Sustained neurohumoral activation involving the sympathetic nervous system, renin-angiotensin-aldosterone system (RAAS), and arginine vasopressin system drives the progression of heart failure through tachycardia and increased vascular resistance.\n\nNatriuretic peptides and catecholamines serve as biomarkers for these pathways and can help identify which patients will benefit from specific therapies. The introduction of sacubitril/valsartan (an angiotensin receptor-neprilysin inhibitor, or ARNI) represents a refinement in RAAS blockade by combining RAAS inhibition with enhanced natriuretic peptide activity through neprilysin blocking.","whyItMatters":"Understanding why the body's own stress responses worsen heart failure is fundamental to modern cardiology. Every major class of heart failure drug — beta blockers, ACE inhibitors, ARBs, mineralocorticoid antagonists, and the newer ARNI sacubitril/valsartan — works by blocking one of these overactive neurohormonal pathways. Natriuretic peptides occupy a dual role as both diagnostic tools and therapeutic targets, making them central to personalized heart failure management.","specificNumbers":"","methodology":"This is a comprehensive narrative review examining the neurohumoral pathways activated in heart failure, their biomarkers, and the therapies directed against them. The review synthesizes published literature on the sympathetic nervous system, RAAS, vasopressin system, natriuretic peptides, and their roles in heart failure pathophysiology and treatment. Key mechanisms are illustrated pictorially.","limitations":"As a narrative review, this paper synthesizes existing knowledge rather than presenting new data. The review covers well-established concepts alongside newer developments, and study selection reflects the authors' perspective. Some emerging neurohormonal targets and newer drugs may not be fully covered. The review focuses on pathophysiology and pharmacology rather than clinical trial outcomes."},{"rthcId":"RPEP-07157","title":"An Atypical Presentation of Dulaglutide-Induced Pancreatitis Complicated by Superior Mesenteric Vein Thrombosis.","authors":"Manuel, Sebastian L; Lin, Frank; Kutty, Sinan M","year":2023,"journal":"Cureus, 15(12), e50051","doi":"10.7759/cureus.50051","pmid":"38186519","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A 57-year-old male with type 2 diabetes developed acute pancreatitis complicated by superior mesenteric vein thrombosis approximately four months after a dose increase of dulaglutide (a GLP-1 receptor agonist). The presentation was atypical — only mild abdominal pain without nausea or vomiting — despite imaging revealing an enlarged pancreatic head and mesenteric vein blood clot. Endoscopic ultrasound with biopsies confirmed acute pancreatitis. The patient was treated with heparin anticoagulation and supportive care, and the GLP-1 agonist was discontinued.","whyItMatters":"With millions of people now taking GLP-1 receptor agonists for diabetes and weight loss, awareness of rare but serious side effects is critical. Pancreatitis is a known potential risk of GLP-1 drugs, but the combination with venous thrombosis and the atypically mild presentation in this case highlights that serious complications can occur with subtle warning signs, especially after dose increases.","specificNumbers":"","methodology":"This is a clinical case report describing the diagnosis, imaging findings, and management of a single patient who developed pancreatitis with mesenteric vein thrombosis while taking dulaglutide. Diagnosis was confirmed by imaging studies and endoscopic ultrasound with tissue biopsies.","limitations":"As a single case report, this cannot establish causation between dulaglutide and the pancreatitis or the venous thrombosis. The temporal association is suggestive but other causes cannot be fully excluded. Case reports provide the lowest level of clinical evidence and serve primarily to alert clinicians to rare possibilities rather than to quantify risk."},{"rthcId":"RPEP-07158","title":"Reduced numbers of naïve CD4 + T cells and an altered CD4/CD8 balance in depressed common variable immune deficiency (CVID) patients. Is thymosin-α1 a possible treatment?","authors":"Manusama, Olivia; Singh, Sajni; Brooimans, Rik A; Wijkhuijs, Annemarie; van der Ent, Marianne; Drexhage, Hemmo A; Dalm, Virgil A","year":2023,"journal":"International immunopharmacology, 119, 110168","doi":"10.1016/j.intimp.2023.110168","pmid":"37086677","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07159","title":"Thymosin alpha 1 - Reimagine its broader applications in the immuno-oncology era.","authors":"Mao, Li","year":2023,"journal":"International immunopharmacology, 117, 109952","doi":"10.1016/j.intimp.2023.109952","pmid":"36871535","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07160","title":"The life and times of endogenous opioid peptides: Updated understanding of synthesis, spatiotemporal dynamics, and the clinical impact in alcohol use disorder.","authors":"Margolis, Elyssa B; Moulton, Madelyn G; Lambeth, Philip S; O'Meara, Matthew J","year":2023,"journal":"Neuropharmacology, 225, 109376","doi":"10.1016/j.neuropharm.2022.109376","pmid":"36516892","tags":["neuropeptides","opioid-peptides"],"studyType":"review","evidenceStrength":"strong","keyFinding":"This comprehensive review maps the current understanding of over two dozen endogenous opioid peptides — the body's natural painkillers and reward signals. Key insights include: the synthesis pathways for endomorphins (a class of opioid peptides) remain debated and only recently proposed; opioid peptide release varies dramatically by brain region, with peptides released from specific neural compartments rather than uniformly; the distance peptides diffuse from release sites and how long they last in brain tissue remain poorly understood.\n\nAs a translational case study, the review examines how naltrexone (NTX) — the FDA-approved medication for alcohol use disorder — works by blocking the effects of these endogenous peptides. Recent research has clarified which specific opioid peptide activities naltrexone prevents, advancing understanding of why this decades-old drug helps reduce alcohol craving and consumption.","whyItMatters":"Despite decades of opioid research, fundamental questions about how the body's own opioid peptides work remain unanswered. This review highlights critical gaps — we still don't fully know how endomorphins are made, how far opioid peptides travel in the brain, or exactly which peptide actions drive specific behaviors. Closing these gaps matters enormously because the opioid system is central to pain, depression, and addiction, and better understanding could lead to more targeted treatments with fewer side effects than current approaches.","specificNumbers":"Over 24 endogenous opioid peptides reviewed · 4 opioid receptor types (mu, delta, kappa, nociceptin) · Naltrexone FDA-approved since 1984 · Multiple brain circuits examined","methodology":"This is a narrative review synthesizing published literature on endogenous opioid peptide synthesis, release dynamics, diffusion, degradation, and clinical relevance. The authors reviewed studies spanning molecular biology, neurophysiology, and clinical pharmacology, with a particular focus on recent findings about endomorphin synthesis and naltrexone's mechanism of action in alcohol use disorder.","limitations":"As a narrative review, this paper synthesizes existing knowledge rather than generating new data. The authors acknowledge that many fundamental questions remain open, particularly regarding endomorphin synthesis, peptide diffusion distances, and the precise temporal dynamics of release. The naltrexone discussion focuses specifically on alcohol use disorder and may not fully represent its mechanisms in other conditions."},{"rthcId":"RPEP-07161","title":"PnPP-15, a Synthetic Peptide Derived from a Toxin from Phoneutria nigriventer Spider Venom, Alleviates Diabetic Neuropathic Pain and Acts Synergistically with Pregabalin in Mice.","authors":"Mariano, Xavier Maia; de Assis Ferreira, Luana Caroline; Almeida-Leite, Camila Megale; de Castro Junior, Célio José; de Lima, Maria Elena","year":2023,"journal":"Toxins, 15(9)","doi":"10.3390/toxins15090560","pmid":"37755986","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07162","title":"Idiopathic intracranial hypertension: expanding our understanding.","authors":"Markey, Keira; Hutchcroft, Christopher; Emsley, Hedley","year":2023,"journal":"Current opinion in neurology, 36(6), 622-630","doi":"10.1097/WCO.0000000000001209","pmid":"37865852","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07163","title":"The Effects of Peptide Receptor Radionuclide Therapy on the Neoplastic and Normal Pituitary.","authors":"Marques, Pedro","year":2023,"journal":"Cancers, 15(10)","doi":"10.3390/cancers15102710","pmid":"37345047","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07164","title":"The Pathophysiological Role of Thymosin β4 in the Kidney Glomerulus.","authors":"Mason, William J; Vasilopoulou, Elisavet","year":2023,"journal":"International journal of molecular sciences, 24(9)","doi":"10.3390/ijms24097684","pmid":"37175390","tags":["thymosin-beta-4","kidney-disease"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"This review examines the role of thymosin beta 4 (Tβ4) in glomerular disease — conditions affecting the kidney's filtration units that are a major driver of chronic kidney disease. Tβ4, which naturally sequesters G-actin (a building block of the cell's structural skeleton), has demonstrated potent anti-inflammatory effects in experimental models of injury across multiple organs including heart, kidney, liver, lung, and eye.\n\nThe review covers both endogenous Tβ4 (what the kidney naturally produces) and exogenous Tβ4 (administered as treatment), examining how each influences glomerular disease progression and the mechanisms behind these effects.","whyItMatters":"Chronic kidney disease from glomerular damage is a massive health burden, often progressing to the point where patients need dialysis or a transplant. Current treatments slow but don't stop this progression. Thymosin beta 4's anti-inflammatory properties across multiple organ systems suggest it could be a promising new therapeutic approach for kidney disease, potentially addressing the inflammatory cascade that drives glomerular damage from bad to worse.","specificNumbers":"Anti-inflammatory effects demonstrated in 5 organ models (heart, kidney, liver, lung, eye) · Glomerular disease = major cause of CKD requiring dialysis/transplant","methodology":"This is a review article that synthesizes existing research on thymosin beta 4's role in glomerular disease. The authors examined published studies on both naturally occurring and externally administered Tβ4 in kidney glomerular disease models, analyzing the proposed mechanisms of action.","limitations":"As a review, this paper synthesizes existing research rather than generating new data. Much of the evidence for Tβ4's anti-inflammatory effects comes from experimental animal models, not human clinical trials. The abstract doesn't specify how many studies were reviewed or their quality. The translation from animal models of glomerular disease to human kidney disease remains uncertain."},{"rthcId":"RPEP-07165","title":"Abaloparatide dose-dependently increases bone mineral density in postmenopausal women with osteoporosis: a phase 2 study.","authors":"Matsumoto, Toshio; Sone, Teruki; Yamashita, Akiko; Inoue, Tetsuo","year":2023,"journal":"Journal of bone and mineral metabolism, 41(6), 807-816","doi":"10.1007/s00774-023-01455-6","pmid":"37505256","tags":[],"studyType":"randomized-controlled-trial","evidenceStrength":"high","keyFinding":"Abaloparatide — a synthetic peptide analog of parathyroid hormone-related protein (PTHrP) — dose-dependently increased bone mineral density at all measured sites in postmenopausal Japanese women with osteoporosis over 48 weeks. The 80 µg dose produced striking results: 11.5% increase in lumbar spine BMD, 2.9% increase at total hip, and 2.4% at femoral neck. Even the lower 40 µg dose showed significant improvement (6.6% lumbar spine).\n\nBone formation markers (serum PINP) increased rapidly — by 67.3% and 140.7% at the 40 and 80 µg doses — indicating strong bone-building activity. Bone resorption markers (serum CTX) increased more slowly and modestly (16.4% and 34.5%), suggesting a favorable anabolic window where bone formation outpaces breakdown. Adverse events were mild to moderate and not dose-dependent.","whyItMatters":"Abaloparatide (brand name Tymlos) is an FDA-approved peptide drug for osteoporosis that competes with teriparatide (Forteo). This phase 2 study in Japanese women establishes dose-response efficacy in an East Asian population, supporting global applicability. The 11.5% lumbar spine BMD increase in under a year is among the strongest anabolic responses seen for any osteoporosis treatment, and the favorable bone formation-to-resorption ratio is a key advantage over some competing therapies.","specificNumbers":"48-week treatment · 40 µg and 80 µg doses vs placebo · Lumbar spine BMD: +6.6% (40 µg) and +11.5% (80 µg) vs placebo · Total hip: +1.6% and +2.9% · Femoral neck: +1.5% and +2.4% · PINP: +67.3% and +140.7% · CTX: +16.4% and +34.5% · Adverse events mild/moderate, not dose-dependent","methodology":"This was a randomized, double-blind, placebo-controlled, dose-finding phase 2 study in postmenopausal Japanese women at high fracture risk. Participants received daily subcutaneous injections of placebo, 40 µg, or 80 µg abaloparatide for 48 weeks. The primary endpoint was change in lumbar spine BMD. Secondary endpoints included total hip and femoral neck BMD at multiple timepoints, and bone turnover markers (PINP for formation, CTX for resorption).","limitations":"The abstract doesn't report the specific number of participants, though phase 2 dose-finding studies typically enroll modest numbers. The study was conducted in Japanese women only, limiting direct generalizability to other populations. 48 weeks is relatively short for an osteoporosis treatment — fracture prevention data requires longer follow-up. Fracture reduction was not an endpoint in this dose-finding study."},{"rthcId":"RPEP-07166","title":"Thymosin α1 interacts with Galectin-1 modulating the β-galactosides affinity and inducing alteration in the biological activity.","authors":"Matteucci, Claudia; Nepravishta, Ridvan; Argaw-Denboba, Ayele; Mandaliti, Walter; Giovinazzo, Alessandro; Petrone, Vita; Balestrieri, Emanuela; Sinibaldi-Vallebona, Paola; Pica, Francesca; Paci, Maurizio; Garaci, Enrico","year":2023,"journal":"International immunopharmacology, 118, 110113","doi":"10.1016/j.intimp.2023.110113","pmid":"37028279","tags":["thymosin-alpha-1","immunology","cancer-research"],"studyType":"Basic Science (In Vitro)","evidenceStrength":"Preliminary","keyFinding":"Researchers discovered a previously unknown interaction between thymosin alpha 1 (Tα1), a thymic immune-modulating peptide, and galectin-1 (Gal-1), a protein involved in cancer progression, immune suppression, and blood vessel formation. Tα1 directly binds to Gal-1 and alters its biological activity in three key ways: it blocks Gal-1's ability to clump red blood cells (hemagglutination), inhibits the formation of new blood vessel structures by endothelial cells, and reduces cancer cell migration in wound healing assays.\n\nPhysico-chemical analysis revealed the molecular details of how Tα1 binds to Gal-1, identifying the specific interaction sites. This is the first study to demonstrate this protein-protein interaction, providing a concrete molecular mechanism that helps explain why Tα1 has such wide-ranging effects across different diseases.","whyItMatters":"Thymosin alpha 1 has been used clinically for decades — particularly for hepatitis B, immune deficiency, and as a vaccine adjuvant — but scientists have struggled to explain how a single peptide can have beneficial effects in so many different conditions. This study identifies a specific molecular target (galectin-1) that could explain much of Tα1's versatility. Since galectin-1 promotes tumor immune evasion, blood vessel growth for tumors, and cancer cell migration, blocking it with Tα1 could be relevant to cancer therapy.","specificNumbers":"Tα1 inhibited Gal-1 hemagglutination · blocked endothelial tube formation · reduced cancer cell migration · molecular interaction characterized by NMR and biophysical methods","methodology":"The study combined molecular biology and biophysical approaches. Hemagglutination assays tested Tα1's ability to block Gal-1's sugar-binding activity. In vitro tube formation assays using endothelial cells assessed anti-angiogenic effects. Wound healing assays measured cancer cell migration. Nuclear magnetic resonance (NMR) spectroscopy and other physico-chemical methods characterized the molecular details of the Tα1-Gal-1 interaction at the structural level.","limitations":"All experiments were conducted in vitro (in lab dishes), so the Tα1-Gal-1 interaction and its functional consequences have not been confirmed in living organisms. The concentrations of Tα1 used in the assays may not reflect physiological or therapeutic levels. The study does not determine whether this interaction is the primary mechanism of Tα1's clinical effects or one of several. Cancer cell migration was tested in a simplified wound healing assay that doesn't capture the full complexity of metastasis."},{"rthcId":"RPEP-07167","title":"Nut-enriched energy restricted diet has potential to decrease hunger in women at cardiometabolic risk: a randomized controlled trial (Brazilian Nuts Study).","authors":"Mayumi Usuda Prado Rocha, Daniela; Paula Silva Caldas, Ana; Simões E Silva, Ana Cristina; Bressan, Josefina; Hermana Miranda Hermsdorff, Helen","year":2023,"journal":"Nutrition research (New York, N.Y.), 109, 35-46","doi":"10.1016/j.nutres.2022.11.003","pmid":"36577255","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07168","title":"GLP-1 RAs and SGLT2i: two antidiabetic agents associated with immune and inflammation modulatory properties through the common AMPK pathway.","authors":"Mazzieri, Alessio; Basta, Giuseppe; Calafiore, Riccardo; Luca, Giovanni","year":2023,"journal":"Frontiers in immunology, 14, 1163288","doi":"10.3389/fimmu.2023.1163288","pmid":"38053992","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07169","title":"Predictors of ≥15% Weight Reduction and Associated Changes in Cardiometabolic Risk Factors With Tirzepatide in Adults With Type 2 Diabetes in SURPASS 1-4.","authors":"Małecki, Maciej T; Batterham, Rachel L; Sattar, Naveed; Levine, Joshua A; Rodríguez, Ángel; Bergman, Brandon K; Wang, Hui; Ghimpeteanu, Gabriela; Lee, Clare J","year":2023,"journal":"Diabetes care, 46(12), 2292-2299","doi":"10.2337/dc23-1135","pmid":"37824793","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07170","title":"Glucagon-like peptide-1: a multi-faceted anti-inflammatory agent.","authors":"Mehdi, Syed Faizan; Pusapati, Suma; Anwar, Muhammad Saad; Lohana, Durga; Kumar, Parkash; Nandula, Savitri Aninditha; Nawaz, Fatima Kausar; Tracey, Kevin; Yang, Huan; LeRoith, Derek; Brownstein, Michael J; Roth, Jesse","year":2023,"journal":"Frontiers in immunology, 14, 1148209","doi":"10.3389/fimmu.2023.1148209","pmid":"37266425","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07171","title":"Differential Blood-Brain Barrier Transport and Cell Uptake of Cyclic Peptides In Vivo and In Vitro.","authors":"Melander, Erik; Eriksson, Camilla; Wellens, Sara; Hosseini, Kimia; Fredriksson, Robert; Gosselet, Fabien; Culot, Maxime; Göransson, Ulf; Hammarlund-Udenaes, Margareta; Loryan, Irena","year":2023,"journal":"Pharmaceutics, 15(5)","doi":"10.3390/pharmaceutics15051507","pmid":"37242750","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07172","title":"The use of liposomes functionalized with the NFL-TBS.40-63 peptide as a targeting agent to cross the in vitro blood-brain barrier and target glioblastoma cells.","authors":"Mellinger, Adélie; Lubitz, Larissa J; Gazaille, Claire; Leneweit, Gero; Bastiat, Guillaume; Lépinoux-Chambaud, Claire; Eyer, Joël","year":2023,"journal":"International journal of pharmaceutics, 646, 123421","doi":"10.1016/j.ijpharm.2023.123421","pmid":"37722495","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07173","title":"Future therapies for obesity.","authors":"Melson, Eka; Miras, Alexander Dimitri; Papamargaritis, Dimitris","year":2023,"journal":"Clinical medicine (London, England), 23(4), 337-346","doi":"10.7861/clinmed.2023-0144","pmid":"37524416","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tirzepatide (GLP-1/GIP dual agonist) marks a new era where pharmacotherapy approaches bariatric surgery-level weight loss. Multiple gut hormone combination strategies are under investigation: GLP-1 + GIP (tirzepatide, already approved), GLP-1 + glucagon (for enhanced energy expenditure and fat metabolism), GLP-1 + GIP + glucagon triple agonists, and amylin analogs. Each additional hormone target complements GLP-1's appetite-suppressing effects through different mechanisms — GIP enhances insulin and may directly affect fat tissue, glucagon increases energy expenditure, and amylin slows gastric emptying and promotes satiety.","whyItMatters":"For decades, the only obesity treatment producing dramatic, sustained weight loss was surgery. The emergence of gut hormone combination drugs that can approach surgical outcomes represents a paradigm shift — potentially making effective obesity treatment available to hundreds of millions of people worldwide who would never qualify for or accept surgery. This review provides a roadmap of what's coming in the next few years.","specificNumbers":"","methodology":"Narrative review published in Clinical Medicine (Royal College of Physicians) covering emerging obesity treatments, with focus on gut hormone combination pharmacotherapy and the multimodal management approach.","limitations":"This is a 2023 review, and the gut hormone drug pipeline is evolving rapidly — some drugs discussed may have advanced, failed, or been superseded by newer candidates. The comparison to bariatric surgery outcomes is based on different trial populations and time frames. Long-term durability of drug-induced weight loss (versus surgery's proven decades-long maintenance) remains uncertain. Cost and access barriers to these expensive medications are not fully addressed."},{"rthcId":"RPEP-07174","title":"Antibiofilm properties of cathelicidin LL-37: an in-depth review.","authors":"Memariani, Hamed; Memariani, Mojtaba","year":2023,"journal":"World journal of microbiology & biotechnology, 39(4), 99","doi":"10.1007/s11274-023-03545-z","pmid":"36781570","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07175","title":"Site-specific methylation on α-N-terminus of peptides through chemical and enzymatic methods.","authors":"Meng, Ying; Huang, Rong","year":2023,"journal":"Methods in enzymology, 684, 113-133","doi":"10.1016/bs.mie.2023.02.008","pmid":"37230586","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07176","title":"Peptide Receptor Radionuclide Therapy (PRRT): Innovations and Improvements.","authors":"Merola, Elettra; Grana, Chiara Maria","year":2023,"journal":"Cancers, 15(11)","doi":"10.3390/cancers15112975","pmid":"37296936","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07177","title":"Ghrelin receptor antagonist JMV2959 blunts cocaine and oxycodone drug-seeking, but not self-administration, in male rats.","authors":"Merritt, Christina R; Garcia, Erik J; Brehm, Victoria D; Fox, Robert G; Moeller, F Gerard; Anastasio, Noelle C; Cunningham, Kathryn A","year":2023,"journal":"Frontiers in pharmacology, 14, 1268366","doi":"10.3389/fphar.2023.1268366","pmid":"37795028","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07178","title":"Snake Venom Components as Therapeutic Drugs in Ischemic Heart Disease.","authors":"Messadi, Erij","year":2023,"journal":"Biomolecules, 13(10)","doi":"10.3390/biom13101539","pmid":"37892221","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07179","title":"Safety and tolerability of monoclonal antibodies targeting the CGRP pathway and gepants in migraine prevention: A systematic review and network meta-analysis.","authors":"Messina, Roberta; Huessler, Eva-Maria; Puledda, Francesca; Haghdoost, Faraidoon; Lebedeva, Elena R; Diener, Hans-Christoph","year":2023,"journal":"Cephalalgia : an international journal of headache, 43(3), 3331024231152169","doi":"10.1177/03331024231152169","pmid":"36786548","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07180","title":"Laser Biostimulation Induces Wound Healing-Promoter β2-Defensin Expression in Human Keratinocytes via Oxidative Stress.","authors":"Migliario, Mario; Yerra, Preetham; Gino, Sarah; Sabbatini, Maurizio; Renò, Filippo","year":2023,"journal":"Antioxidants (Basel, Switzerland), 12(8)","doi":"10.3390/antiox12081550","pmid":"37627545","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07181","title":"Effects of Kisspeptin on Sexual Brain Processing and Penile Tumescence in Men With Hypoactive Sexual Desire Disorder: A Randomized Clinical Trial.","authors":"Mills, Edouard G; Wall, Matthew B; Alexander, Emma C; Sherwood, Robin A; Sheridan, Rebecca; Byers, Alexander; Sherwood, Karolina; Clarke, Sophie A; Sheridan, Alexander; Salem, Victoria; Owen, Benedict M; Dhillo, Waljit S","year":2023,"journal":"JAMA network open, 6(2), e2255700","doi":"10.1001/jamanetworkopen.2022.55700","pmid":"36735255","tags":["neuropeptides"],"studyType":"human-rct","evidenceStrength":"strong","keyFinding":"In 32 men with HSDD, kisspeptin modulated sexual brain processing, enhanced penile tumescence to erotic videos, and increased happiness compared to placebo.","whyItMatters":"First RCT demonstrating kisspeptin's effects on sexual brain processing in men with clinical sexual dysfunction, showing both neural and physiological (tumescence) outcomes.","specificNumbers":"32 men with HSDD; enhanced penile tumescence; increased happiness scores","methodology":"Randomized, double-blind, placebo-controlled crossover trial with fMRI in men with HSDD.","limitations":"Single session. Small sample. Same research group as prior studies."},{"rthcId":"RPEP-07182","title":"Current findings on the efficacy of incretin-based drugs for diabetic kidney disease: A narrative review.","authors":"Mima, Akira; Nomura, Atsuo; Fujii, Takeshi","year":2023,"journal":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 165, 115032","doi":"10.1016/j.biopha.2023.115032","pmid":"37331253","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07183","title":"Thymosin alpha 1 restores the immune homeostasis in lymphocytes during Post-Acute sequelae of SARS-CoV-2 infection.","authors":"Minutolo, Antonella; Petrone, Vita; Fanelli, Marialaura; Maracchioni, Christian; Giudice, Martina; Teti, Elisabetta; Coppola, Luigi; Sorace, Chiara; Iannetta, Marco; Tony Miele, Martino; Bernardini, Sergio; Mastino, Antonio; Sinibaldi Vallebona, Paola; Balestrieri, Emanuela; Andreoni, Massimo; Sarmati, Loredana; Grelli, Sandro; Garaci, Enrico; Matteucci, Claudia","year":2023,"journal":"International immunopharmacology, 118, 110055","doi":"10.1016/j.intimp.2023.110055","pmid":"36989892","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07184","title":"Cathelicidin Antimicrobial Peptide LL37 Induces Toll-Like Receptor 8 and Amplifies IL-36γ and IL-17C in Human Keratinocytes.","authors":"Miura, Shunsuke; Garcet, Sandra; Li, Xuan; Cueto, Inna; Salud-Gnilo, Charissa; Kunjravia, Norma; Yamamura, Kazuhiko; Gonzalez, Juana; Murai-Yamamura, Mika; Rambhia, Darshna; Krueger, James G","year":2023,"journal":"The Journal of investigative dermatology, 143(5), 832-841.e4","doi":"10.1016/j.jid.2022.10.017","pmid":"36496195","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07185","title":"In vitro selection of macrocyclic peptide inhibitors containing cyclic γ2,4-amino acids targeting the SARS-CoV-2 main protease.","authors":"Miura, Takashi; Malla, Tika R; Owen, C David; Tumber, Anthony; Brewitz, Lennart; McDonough, Michael A; Salah, Eidarus; Terasaka, Naohiro; Katoh, Takayuki; Lukacik, Petra; Strain-Damerell, Claire; Mikolajek, Halina; Walsh, Martin A; Kawamura, Akane; Schofield, Christopher J; Suga, Hiroaki","year":2023,"journal":"Nature chemistry, 15(7), 998-1005","doi":"10.1038/s41557-023-01205-1","pmid":"37217786","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07186","title":"Arginine-Rich Cell-Penetrating Peptide-Mediated Transduction of Mouse Nasal Cells with FOXP3 Protein Alleviates Allergic Rhinitis.","authors":"Miwa, Toru; Takemiya, Yumi; Amesara, Kazuki; Kawai, Hiroko; Teranishi, Yuichi","year":2023,"journal":"Pharmaceutics, 15(6)","doi":"10.3390/pharmaceutics15061770","pmid":"37376217","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07187","title":"Tirzepatide-Induced Injection Site Reaction.","authors":"Mizumoto, Junki","year":2023,"journal":"Cureus, 15(9), e45181","doi":"10.7759/cureus.45181","pmid":"37842452","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A man in his 70s developed an injection site rash on his lower abdomen after switching from dulaglutide (a GLP-1 RA) to tirzepatide (a dual GIP/GLP-1 RA). The rash resolved after stopping tirzepatide. Notably, the patient had tolerated dulaglutide without any injection site reactions, indicating a tirzepatide-specific skin reaction. This was reported as the first documented case of tirzepatide-induced injection site reaction.","whyItMatters":"As tirzepatide rapidly gains prescriptions for diabetes and obesity, documenting its adverse effects is important for clinicians. This case shows that patients who tolerate one GLP-1 RA may still develop reactions to tirzepatide, which has a different molecular structure as a dual GIP/GLP-1 receptor agonist. Clinicians should be aware that switching between peptide drugs in this class doesn't guarantee the same tolerability profile.","specificNumbers":"n=1 · male in his 70s · rash at injection site on lower abdomen · resolved after stopping tirzepatide · no reaction with prior dulaglutide use","methodology":"This is a single case report documenting the clinical presentation, timeline, and resolution of an injection site reaction after switching from dulaglutide to tirzepatide.","limitations":"As a single case report, this represents an isolated observation that cannot establish the frequency or risk factors for tirzepatide injection site reactions. No allergy testing or skin biopsy was described to characterize the nature of the reaction. The mechanism of the tirzepatide-specific reaction was not investigated."},{"rthcId":"RPEP-07188","title":"The Present and the Future of Medical Therapies for Adenomyosis: A Narrative Review.","authors":"Moawad, Gaby; Youssef, Youssef; Fruscalzo, Arrigo; Faysal, Hani; Kheil, Mira; Pirtea, Paul; Guani, Benedetta; Ayoubi, Jean Marc; Feki, Anis","year":2023,"journal":"Journal of clinical medicine, 12(19)","doi":"10.3390/jcm12196130","pmid":"37834773","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07189","title":"Cost per Patient Achieving Treatment Targets and Number Needed to Treat with Tirzepatide Versus Semaglutide 1 mg in Patients with Type 2 Diabetes in the United States.","authors":"Mody, Reema R; Meyer, Kellie L; Ward, Jennifer M; O'Day, Ken B","year":2023,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 14(12), 2045-2055","doi":"10.1007/s13300-023-01470-w","pmid":"37770706","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07190","title":"AdenPredictor: accurate prediction of the adenylation domain specificity of nonribosomal peptide biosynthetic gene clusters in microbial genomes.","authors":"Mongia, Mihir; Baral, Romel; Adduri, Abhinav; Yan, Donghui; Liu, Yudong; Bian, Yuying; Kim, Paul; Behsaz, Bahar; Mohimani, Hosein","year":2023,"journal":"Bioinformatics (Oxford, England), 39(39 Suppl 1), i40-i46","doi":"10.1093/bioinformatics/btad235","pmid":"37387149","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07191","title":"Antibacterial Efficacy of a Chitosan-Based Hydrogel Modified With Epsilon-Poly-l-Lysine Against Pseudomonas aeruginosa in a Murine-Infected Burn Wound Model.","authors":"Moon, Andrea Y; Bailey, Emily J; Polanco, Jonilee A; Kurata, Wendy E; Pierce, Lisa M","year":2023,"journal":"Military medicine, 188(Suppl 6), 52-60","doi":"10.1093/milmed/usad013","pmid":"37948238","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07192","title":"Decreased salivary beta-defensin 2 in children with asthma after treatment with corticosteroid inhaler.","authors":"Moosavi, M-S; Hosseinizade, P-S; Panahi, G; Shariat, M","year":2023,"journal":"European archives of paediatric dentistry : official journal of the European Academy of Paediatric Dentistry, 24(2), 249-254","doi":"10.1007/s40368-022-00776-w","pmid":"36749545","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Salivary beta-defensin 2 levels were significantly lower in children with asthma after 4 weeks of inhaled corticosteroid therapy compared to pre-treatment levels. Salivary flow rate did not change significantly between the two time points, indicating the reduction in this antimicrobial peptide was not simply due to reduced saliva production but likely a direct effect of corticosteroid treatment on defensin expression.","whyItMatters":"Beta-defensin 2 is a key antimicrobial peptide in the mouth's innate immune defense. Its reduction after corticosteroid inhaler use could help explain why asthmatic children on inhaler therapy are more susceptible to oral infections like candidiasis. This finding supports the recommendation for regular dental monitoring in these patients.","specificNumbers":"Saliva sampled at 2 time points · 4 weeks of corticosteroid inhaler therapy · Significant decrease in beta-defensin 2 · No change in salivary flow rate","methodology":"Cohort study of children diagnosed with asthma at a children's medical center. Saliva samples were collected at diagnosis (before treatment) and again 4 weeks after starting inhaled corticosteroid therapy. Beta-defensin 2 levels were measured using ELISA, and salivary flow rate was also assessed at both time points.","limitations":"The abstract does not report the sample size, specific beta-defensin 2 concentrations, or effect sizes. The 4-week follow-up period is relatively short, so longer-term effects are unknown. The study lacked a control group of healthy children or asthmatic children not receiving corticosteroids, making it harder to isolate the drug's effect from disease progression."},{"rthcId":"RPEP-07193","title":"A zone-of-inhibition assay to screen for humoral antimicrobial activity in mosquito hemolymph.","authors":"Morejon, Bianca; Michel, Kristin","year":2023,"journal":"Frontiers in cellular and infection microbiology, 13, 891577","doi":"10.3389/fcimb.2023.891577","pmid":"36779191","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07194","title":"Amphiphilic Cell-Penetrating Peptides Containing Arginine and Hydrophobic Residues as Protein Delivery Agents.","authors":"Moreno, Jonathan; Zoghebi, Khalid; Salehi, David; Kim, Lois; Shoushtari, Sorour Khayyatnejad; Tiwari, Rakesh K; Parang, Keykavous","year":2023,"journal":"Pharmaceuticals (Basel, Switzerland), 16(3)","doi":"10.3390/ph16030469","pmid":"36986567","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07195","title":"Development of Bifunctional, Raman Active Diyne-Girder Stapled α-Helical Peptides.","authors":"Morgan, Danielle C; McDougall, Laura; Knuhtsen, Astrid; Jamieson, Andrew G","year":2023,"journal":"Chemistry (Weinheim an der Bergstrasse, Germany), 29(41), e202300855","doi":"10.1002/chem.202300855","pmid":"37130830","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07196","title":"Novel cannabinoid receptor 1 inverse agonist CRB-913 enhances efficacy of tirzepatide, semaglutide, and liraglutidein the diet-induced obesity mouse model.","authors":"Morningstar, Marshall; Kolodziej, Andrew; Ferreira, Suzie; Blumen, Tracy; Brake, Rachael; Cohen, Yuval","year":2023,"journal":"Obesity (Silver Spring, Md.), 31(11), 2676-2688","doi":"10.1002/oby.23902","pmid":"37840407","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CRB-913, a novel cannabinoid receptor 1 (CB1R) inverse agonist with 9.5-fold lower brain penetration than rimonabant, enhanced the weight loss effects of three GLP-1 peptide drugs in obese mice. Combinations produced body weight reductions of -32.6% with tirzepatide, -28.8% with semaglutide, and -16.8% with liraglutide by day 18. CRB-913 alone achieved -22% weight loss. Combinations also improved body fat content, liver triglycerides, and liver fat deposits. CRB-913's reduced brain penetration aims to avoid the psychiatric side effects that derailed the original CB1R blocker rimonabant.","whyItMatters":"Even the most effective GLP-1 drugs don't achieve sufficient weight loss for all patients. This study demonstrates that combining GLP-1 peptide agonists with a peripheral CB1R blocker can dramatically enhance weight loss beyond what either approach achieves alone. By designing CRB-913 to stay out of the brain, the researchers addressed the safety concerns that killed rimonabant — potentially unlocking an entire drug class for combination with peptide therapies.","specificNumbers":"CRB-913 alone: -22% body weight · + tirzepatide: -32.6% · + semaglutide: -28.8% · + liraglutide: -16.8% · 18-day treatment · 3.8-fold greater plasma exposure vs rimonabant · 9.5-fold lower brain levels vs rimonabant","methodology":"CRB-913 was pharmacokinetically characterized and compared to rimonabant for plasma exposure and brain penetration. Dose-response was tested as monotherapy in diet-induced obese (DIO) mice. Combination studies tested CRB-913 (2.5 mg/kg) with tirzepatide, semaglutide, or liraglutide in DIO mice over 18 days. Body weight, body fat content, liver triglycerides, and liver fat deposits were measured.","limitations":"This is a mouse study, and weight loss in DIO mice may not directly predict human outcomes. The 18-day treatment period is short — long-term efficacy and safety of the combination are unknown. While CRB-913 has reduced brain penetration, it is not zero — potential psychiatric effects in humans need evaluation. The specific mechanism of synergy between CB1R blockade and GLP-1 RA signaling was not fully elucidated."},{"rthcId":"RPEP-07197","title":"Exploring Cell-Penetrating Peptides as Penetration Enhancers in Eye Drop Formulations Using a Reconstructed Human Corneal Epithelial Model.","authors":"Morofuji, Ryo; Enomoto, Hiroshi; Honda, Takahiro; Oyama, Yuki; Ishida, Reiji; Kudo, Kazuhiro; Okabe, Komei","year":2023,"journal":"Biological & pharmaceutical bulletin, 46(12), 1720-1730","doi":"10.1248/bpb.b23-00457","pmid":"38044130","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07198","title":"Venoms classification and therapeutic uses: a narrative review.","authors":"Morsy, M A; Gupta, S; Dora, C P; Jhawat, V; Dhanawat, M; Mehta, D; Gupta, K; Nair, A B; El-Daly, M","year":2023,"journal":"European review for medical and pharmacological sciences, 27(4), 1633-1653","doi":"10.26355/eurrev_202302_31408","pmid":"36876699","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07199","title":"A new class of peptides from wasp venom: a pathway to antiepileptic/neuroprotective drugs.","authors":"Mortari, Márcia Renata; Cunha, Alexandra O S; Dos Anjos, Lilian C; Amaral, Henrique O; Quintanilha, Maria Varela Torres; Gelfuso, Erica A; Homem-de-Mello, Mauricio; de Almeida, Hugo; Rego, Solange; Maigret, Bernard; Lopes, Norberto P; Dos Santos, Wagner F","year":2023,"journal":"Brain communications, 5(1), fcad016","doi":"10.1093/braincomms/fcad016","pmid":"36844150","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07200","title":"Resistance is futile: targeting multidrug-resistant bacteria with de novo Cys-rich cyclic polypeptides.","authors":"Mourenza, Alvaro; Ganesan, Rajasekaran; Camarero, Julio A","year":2023,"journal":"RSC chemical biology, 4(10), 722-735","doi":"10.1039/d3cb00015j","pmid":"37799576","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07201","title":"Efficacy and Safety of Anti-calcitonin Gene-Related Peptide (CGRP) Monoclonal Antibodies in Preventing Migraines: A Systematic Review.","authors":"Muddam, Meghana Reddy; Obajeun, Omobolanle A; Abaza, Abdelrahman; Jaramillo, Arturo P; Sid Idris, Faten; Anis Shaikh, Humna; Vahora, Ilma; Moparthi, Kiran Prasad; Al Rushaidi, Majdah T; Nath, Tuheen Sankar","year":2023,"journal":"Cureus, 15(9), e45560","doi":"10.7759/cureus.45560","pmid":"37868560","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07202","title":"Exploring the Limits of Cyanobactin Macrocyclase PatGmac: Cyclization of PawS-Derived Peptide Sunflower Trypsin Inhibitor-1 and Cyclotide Kalata B1.","authors":"Muhammad, Taj; Houssen, Wael E; Thomas, Louise; Alexandru-Crivac, Cristina-Nicoleta; Gunasekera, Sunithi; Jaspars, Marcel; Göransson, Ulf","year":2023,"journal":"Journal of natural products, 86(3), 566-573","doi":"10.1021/acs.jnatprod.2c01158","pmid":"36917740","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07203","title":"Amyloid-Inspired Engineered Multidomain Amphiphilic Injectable Peptide Hydrogel─An Excellent Antibacterial, Angiogenic, and Biocompatible Wound Healing Material.","authors":"Mukherjee, Nabanita; Ghosh, Satyajit; Sarkar, Jayita; Roy, Rajsekhar; Nandi, Debasmita; Ghosh, Surajit","year":2023,"journal":"ACS applied materials & interfaces, 15(28), 33457-33479","doi":"10.1021/acsami.3c06599","pmid":"37429020","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07204","title":"Substance P-Derived Extracellular-Matrix-Mimicking Peptide Hydrogel as a Cytocompatible Biomaterial Platform.","authors":"Mukherjee, Nabanita; Ghosh, Surajit","year":2023,"journal":"Chembiochem : a European journal of chemical biology, 24(18), e202300286","doi":"10.1002/cbic.202300286","pmid":"37461811","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07205","title":"Effects of GLP-1 agonists and SGLT2 inhibitors during pregnancy and lactation on offspring outcomes: a systematic review of the evidence.","authors":"Muller, Dion R P; Stenvers, Dirk J; Malekzadeh, Arjan; Holleman, Frederik; Painter, Rebecca C; Siegelaar, Sarah E","year":2023,"journal":"Frontiers in endocrinology, 14, 1215356","doi":"10.3389/fendo.2023.1215356","pmid":"37881498","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07206","title":"Characterisation of Bioactive Peptides from Red Alga Gracilariopsis chorda.","authors":"Mune Mune, Martin Alain; Miyabe, Yoshikatsu; Shimizu, Takeshi; Matsui, Wataru; Kumagai, Yuya; Kishimura, Hideki","year":2023,"journal":"Marine drugs, 21(1)","doi":"10.3390/md21010049","pmid":"36662222","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Water-soluble protein from the red alga Gracilariopsis chorda, when hydrolyzed by thermolysin, produced peptides with 92% ACE (angiotensin-converting enzyme) inhibitory activity, substantially outperforming its DPP-IV inhibitory and antioxidant (DPPH scavenging) activities. Two novel ACE-inhibitory peptides were identified: IDHY and LVVER. Molecular docking analysis showed IDHY to be a particularly promising ACE inhibitor. The source proteins — phycobiliproteins and RuBisCo — contain high proportions of hydrophobic (31.0–46.5%) and aromatic (5.1–46.5%) amino acid residues, favorable for ACE-inhibitory peptide generation. Most ACE-inhibitory peptide sequences were located in highly solvent-accessible α-helix regions of the parent proteins.","whyItMatters":"ACE inhibitors are one of the most important drug classes for treating high blood pressure and heart disease. Discovering natural peptides from marine algae that can inhibit ACE could lead to food-derived alternatives or supplements with blood pressure-lowering potential, and red algae represent an abundant, sustainable source of these bioactive peptides.","specificNumbers":"92% ACE inhibition · 2 novel peptides (IDHY, LVVER) · 31.0–46.5% hydrophobic amino acids · 5.1–46.5% aromatic amino acids","methodology":"Laboratory study. Water-soluble proteins were extracted from the red alga G. chorda and hydrolyzed using thermolysin enzyme. The resulting peptides were tested for ACE inhibitory activity, DPP-IV inhibitory activity, and antioxidant (DPPH scavenging) activity. Novel peptides were identified and their interaction with human ACE was modeled using molecular docking. In silico analysis of the 3D protein structures identified structural features that favor ACE-inhibitory peptide release during digestion.","limitations":"This is an in vitro and computational study — the ACE inhibitory activity was measured in the lab, not in living organisms. The peptides have not been tested in animal models or human clinical trials, so their actual blood pressure-lowering effect in the body is unknown. Peptide bioavailability (whether they survive digestion and reach the bloodstream intact) was not assessed."},{"rthcId":"RPEP-07207","title":"Thymosin β4 preserves vascular smooth muscle phenotype in atherosclerosis via regulation of low density lipoprotein related protein 1 (LRP1).","authors":"Munshaw, Sonali; Redpath, Andia N; Pike, Benjamin T; Smart, Nicola","year":2023,"journal":"International immunopharmacology, 115, 109702","doi":"10.1016/j.intimp.2023.109702","pmid":"37724952","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07208","title":"Design and structural validation of peptide-drug conjugate ligands of the kappa-opioid receptor.","authors":"Muratspahić, Edin; Deibler, Kristine; Han, Jianming; Tomašević, Nataša; Jadhav, Kirtikumar B; Olivé-Marti, Aina-Leonor; Hochrainer, Nadine; Hellinger, Roland; Koehbach, Johannes; Fay, Jonathan F; Rahman, Mohammad Homaidur; Hegazy, Lamees; Craven, Timothy W; Varga, Balazs R; Bhardwaj, Gaurav; Appourchaux, Kevin; Majumdar, Susruta; Muttenthaler, Markus; Hosseinzadeh, Parisa; Craik, David J; Spetea, Mariana; Che, Tao; Baker, David; Gruber, Christian W","year":2023,"journal":"Nature communications, 14(1), 8064","doi":"10.1038/s41467-023-43718-w","pmid":"38052802","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07209","title":"Prior authorization requirements for calcitonin gene-related peptide antagonists.","authors":"Musial, Lindsay; Kheloussi, Steven","year":2023,"journal":"The American journal of managed care, 29(4), e117-e123","doi":"10.37765/ajmc.2023.89352","pmid":"37104838","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07210","title":"Effectiveness and safety of anti-CGRP monoclonal antibodies in patients over 65 years: a real-life multicentre analysis of 162 patients.","authors":"Muñoz-Vendrell, Albert; Campoy, Sergio; Caronna, Edoardo; Alpuente, Alicia; Torres-Ferrus, Marta; Nieves Castellanos, Candela; Olivier, Marina; Campdelacreu, Jaume; Prat, Joan; Camiña Muñiz, Javier; Molina Martínez, Francisco José; Mínguez-Olaondo, Ane; Ruibal Salgado, Marta; Santos Lasaosa, Sonia; Navarro Pérez, María Pilar; Morollón, Noemí; López Bravo, Alba; Cano Sánchez, Luis Miguel; García-Sánchez, Sonia María; García-Ull, Jésica; Rubio-Flores, Laura; Gonzalez-Martinez, Alicia; Quintas, Sonia; Echavarría Íñiguez, Ana; Gil Luque, Sendoa; Castro-Sánchez, María Victoria; Adell Ortega, Vanesa; García Alhama, Jessica; Berrocal-Izquierdo, Nuria; Belvís, Robert; Díaz-Insa, Samuel; Pozo-Rosich, Patricia; Huerta-Villanueva, Mariano","year":2023,"journal":"The journal of headache and pain, 24(1), 63","doi":"10.1186/s10194-023-01585-2","pmid":"37268904","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07211","title":"Type I IFNs link skin-associated dysbiotic commensal bacteria to pathogenic inflammation and angiogenesis in rosacea.","authors":"Mylonas, Alessio; Hawerkamp, Heike C; Wang, Yichen; Chen, Jiaqi; Messina, Francesco; Demaria, Olivier; Meller, Stephan; Homey, Bernhard; Di Domizio, Jeremy; Mazzolai, Lucia; Hovnanian, Alain; Gilliet, Michel; Conrad, Curdin","year":2023,"journal":"JCI insight, 8(4)","doi":"10.1172/jci.insight.151846","pmid":"36633910","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07212","title":"Provocative non-canonical roles of p53 and AKT signaling: A role for Thymosin β4 in medulloblastoma.","authors":"Naeem, Aisha; Knoer, Grace; Avantaggiati, Maria Laura; Rodriguez, Olga; Albanese, Chris","year":2023,"journal":"International immunopharmacology, 116, 109785","doi":"10.1016/j.intimp.2023.109785","pmid":"36720193","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review presents evidence that p53 and AKT signaling pathways can have non-canonical (opposite to expected) functions in cancer: p53 can promote cell survival and AKT can promote cell death under certain conditions. The authors' own research found that Thymosin beta-4 (Tβ4) mediates chemosensitivity in medulloblastoma cells through an AKT-p53 interaction, suggesting the peptide could be leveraged to enhance drug sensitivity.\n\nThese context-dependent, interchangeable functions of p53 and AKT may be therapeutically exploitable, and Thymosin beta-4's role in modulating this interaction represents a potential new approach to treating medulloblastoma.","whyItMatters":"Medulloblastoma is the most common malignant brain tumor in children, and treatment often involves aggressive chemotherapy with significant side effects. If Thymosin beta-4 can enhance chemotherapy sensitivity, it could allow lower drug doses with the same efficacy, potentially reducing the severe long-term side effects that childhood brain cancer survivors face.","specificNumbers":"","methodology":"This is a review article synthesizing published literature on non-canonical p53 and AKT functions in cancer, combined with the authors' own experimental findings on Thymosin beta-4 in medulloblastoma cell models. The review discusses factors and circumstances that mediate these unconventional signaling behaviors.","limitations":"This is primarily a review article with the Thymosin beta-4 findings based on cell culture experiments. No in vivo or clinical data on Thymosin beta-4 in medulloblastoma was presented. The non-canonical behaviors of p53 and AKT are context-dependent, making it difficult to predict outcomes in different tumor subtypes. Translation to clinical application would require extensive preclinical and clinical testing."},{"rthcId":"RPEP-07213","title":"Semaglutide and cancer: A systematic review and meta-analysis.","authors":"Nagendra, Lakshmi; Bg, Harish; Sharma, Meha; Dutta, Deep","year":2023,"journal":"Diabetes & metabolic syndrome, 17(9), 102834","doi":"10.1016/j.dsx.2023.102834","pmid":"37531876","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07214","title":"A review of bioactive peptides as functional food ingredients: mechanisms of action and their applications in active packaging and food quality improvement.","authors":"Najafian, Leila","year":2023,"journal":"Food & function, 14(13), 5835-5857","doi":"10.1039/d3fo00362k","pmid":"37310352","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07215","title":"Competition between skin antimicrobial peptides and commensal bacteria in type 2 inflammation enables survival of S. aureus.","authors":"Nakatsuji, Teruaki; Brinton, Samantha L; Cavagnero, Kellen J; O'Neill, Alan M; Chen, Yang; Dokoshi, Tatsuya; Butcher, Anna M; Osuoji, Olive C; Shafiq, Faiza; Espinoza, Josh L; Dupont, Christopher L; Hata, Tissa R; Gallo, Richard L","year":2023,"journal":"Cell reports, 42(5), 112494","doi":"10.1016/j.celrep.2023.112494","pmid":"37167061","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The study reveals a surprising mechanism by which allergic inflammation enables S. aureus colonization:\n\n1. Th2 (allergic) inflammation via IL-4Rα activation reduces antimicrobial peptide production\n2. This partial AMP reduction selectively kills coagulase-negative Staphylococcus (CoNS) strains that normally produce natural antibiotics against S. aureus\n3. Without these protective bacteria, antibiotic-non-producing CoNS and S. aureus expand — recapitulating the microbiome seen in human atopic dermatitis\n4. In Camp-/- mice or after topical steroids (which further suppress AMPs), paradoxically the antibiotic-producing CoNS survive because they're no longer selectively targeted\n5. In Th17 inflammation, high AMP levels directly kill S. aureus — explaining why psoriasis patients (Th17-dominant) rarely get staph infections\n\nThis demonstrates a competitive dynamic where both host AMPs and bacterial-produced antibiotics cooperate to control S. aureus.","whyItMatters":"Atopic dermatitis affects up to 20% of children and 3% of adults, and S. aureus colonization is its most common complication — worsening flares and sometimes causing serious infections. This study reveals why: the body's own antimicrobial peptides, reduced by allergic inflammation, inadvertently eliminate protective skin bacteria. This opens new therapeutic strategies: instead of just treating the staph infection, we could restore protective AMP levels or apply beneficial bacteria to re-establish the natural anti-staph defense.","specificNumbers":"","methodology":"Researchers used single-cell RNA sequencing of Il4ra-/- mice combined with skin microbiome analysis to understand how allergic inflammation affects antimicrobial peptide production and the skin microbiome. They compared outcomes in different immune conditions (Th2 vs Th17 inflammation) and genetic backgrounds (Camp-/- mice lacking cathelicidin), and correlated findings with the microbiome composition of human atopic dermatitis patients.","limitations":"Much of the study was conducted in mouse models, which have different skin microbiomes and immune responses than humans. The translation from murine to human atopic dermatitis, while supported by correlative microbiome data, needs direct clinical validation. The study focuses on specific AMP types (cathelicidin) and may not capture the full complexity of human skin antimicrobial defense. The paradoxical protective effect of further AMP inhibition (steroids, Camp-/-) needs careful interpretation to avoid inappropriate clinical extrapolation."},{"rthcId":"RPEP-07216","title":"Challenges and future perspective of antisense therapy for spinal muscular atrophy: A review.","authors":"Nakevska, Zorica; Yokota, Toshifumi","year":2023,"journal":"European journal of cell biology, 102(2), 151326","doi":"10.1016/j.ejcb.2023.151326","pmid":"37295266","tags":["cell-penetrating-peptides","drug-delivery"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Nusinersen (Spinraza), the first FDA-approved antisense therapy for spinal muscular atrophy, faces significant delivery challenges because it must be injected directly into the spinal canal. Peptide-conjugated phosphorodiamidate morpholino oligomers (PPMOs) — antisense drugs linked to cell-penetrating peptides like Pip and DG9 — offer a potential solution by improving both intracellular uptake and systemic distribution.\n\nThe review traces how SMA is caused by mutations in the SMN1 gene, leaving patients dependent on the backup SMN2 gene that produces mostly non-functional protein (~90% defective). Antisense therapy corrects SMN2 splicing to produce functional SMN protein, but getting the drug into motor neurons throughout the body remains the central challenge that peptide conjugation aims to solve.","whyItMatters":"Spinal muscular atrophy is the most common genetic cause of death in infants. While nusinersen was a breakthrough, its requirement for repeated intrathecal injections (directly into the spinal fluid) limits accessibility and comfort. Cell-penetrating peptides attached to antisense drugs could enable systemic delivery — potentially turning a spinal injection into a simpler intravenous treatment.","specificNumbers":"~90% of SMN2 protein is non-functional · FDA approved nusinersen 2016 · EMA approved 2017","methodology":"Narrative review covering the history, development milestones, current therapeutic approaches, and emerging peptide-conjugated delivery strategies for antisense therapy in spinal muscular atrophy.","limitations":"As a narrative review, this paper summarizes existing research without performing quantitative analysis. PPMOs for SMA are still largely preclinical, so the delivery advantages described are based on early-stage data rather than completed clinical trials."},{"rthcId":"RPEP-07217","title":"Scorpion Venom as a Source of Antimicrobial Peptides: Overview of Biomolecule Separation, Analysis and Characterization Methods.","authors":"Nasr, Sara; Borges, Adolfo; Sahyoun, Christina; Nasr, Riad; Roufayel, Rabih; Legros, Christian; Sabatier, Jean-Marc; Fajloun, Ziad","year":2023,"journal":"Antibiotics (Basel, Switzerland), 12(9)","doi":"10.3390/antibiotics12091380","pmid":"37760677","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07218","title":"Heart Failure With Preserved Ejection Fraction: Current Status of Daily Clinical Practice in Indonesia.","authors":"Nauli, Siti E; Prima Putri, Vebiona K; Arifianto, Habibie; Prameswari, Hawani S; Lubis, Anggia C; Zulkarnain, Edrian; Hasanah, Dian Y; Dewi Yamin, Paskariatne P; Dewi, Triwedya I; Irnizarifka","year":2023,"journal":"Cureus, 15(4), e38086","doi":"10.7759/cureus.38086","pmid":"37257168","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07219","title":"A Method for Using Cell-Penetrating Peptides for Loading Plasmid DNA into Secreted Extracellular Vesicles.","authors":"Nebogatova, Jekaterina; Härk, Heleri Heike; Puskar, Anett; Porosk, Ly; Guazzi, Paolo; Dowaidar, Moataz; Langel, Ülo; Kurrikoff, Kaido","year":2023,"journal":"Biomolecules, 13(12)","doi":"10.3390/biom13121751","pmid":"38136622","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07220","title":"Anti-Müllerian hormone for the diagnosis and prediction of menopause: a systematic review.","authors":"Nelson, Scott M; Davis, Susan R; Kalantaridou, Sophia; Lumsden, Mary Ann; Panay, Nick; Anderson, Richard A","year":2023,"journal":"Human reproduction update, 29(3), 327-346","doi":"10.1093/humupd/dmac045","pmid":"36651193","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07221","title":"Immunological effects of heated intraperitoneal chemotherapy can be augmented by thymosin α1.","authors":"Nevo, Nadav; Lee Goldstein, Adam; Bar-David, Shoshi; Abu-Abeid, Adam; Dayan, Danit; Lahat, Guy; Nizri, Eran","year":2023,"journal":"International immunopharmacology, 116, 109829","doi":"10.1016/j.intimp.2023.109829","pmid":"36758296","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07222","title":"Incretins (GLP-1 receptor agonists and dual/triple agonists) and the liver.","authors":"Newsome, Philip N; Ambery, Phil","year":2023,"journal":"Journal of hepatology, 79(6), 1557-1565","doi":"10.1016/j.jhep.2023.07.033","pmid":"37562748","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 receptor agonists have shown promise in treating MASH (formerly NASH) in phase II trials and are now in phase III testing. Newer dual and triple agonists combining GLP-1 with glucagon and/or GIP activity have demonstrated improvements in weight, insulin resistance, and non-invasive liver markers. However, it remains unclear whether these drugs act directly on liver disease or primarily work through upstream weight loss and metabolic improvements. The authors suggest that combining gut hormone agonists with agents that directly target fibrosis (like FGF21 or pan-PPAR agonists) may be the most effective strategy.","whyItMatters":"MASH is a leading cause of liver disease worldwide, driven primarily by obesity and insulin resistance. The GLP-1 drug class — including semaglutide and tirzepatide — represents one of the most promising therapeutic approaches, but the field is still working out which combinations work best. This review maps the current landscape of incretin-based liver therapies and identifies the key open questions that will shape clinical trials for years to come.","specificNumbers":"","methodology":"This is a narrative review article that synthesizes evidence from published clinical trials (phase IIa, IIb, and early phase III) of GLP-1 receptor agonists and multi-agonist peptides in patients with MASH. It evaluates both the direct and indirect mechanisms of action and discusses combination therapy strategies.","limitations":"As a narrative review, this paper does not perform quantitative analysis or meta-analysis of the trials discussed. The optimal ratios of GLP-1, GIP, and glucagon agonism in multi-agonist drugs remain unresolved. The review acknowledges significant uncertainty about whether GIP agonism or antagonism is the better approach, and notes that combination therapies bring cumulative side-effect and cost concerns."},{"rthcId":"RPEP-07223","title":"Antioxidant Properties and Prediction of Bioactive Peptides Produced from Flixweed (sophia, Descurainis sophia L.) and Camelina (Camelina sativa (L.) Crantz) Seed Meal: Integrated In Vitro and In Silico Studies.","authors":"Ngo, Na Thi Ty; Senadheera, Tharindu R L; Shahidi, Fereidoon","year":2023,"journal":"Plants (Basel, Switzerland), 12(20)","doi":"10.3390/plants12203575","pmid":"37896038","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07224","title":"Neurokinin-2 receptor negatively modulates substance P responses by forming complex with Neurokinin-1 receptor.","authors":"Nguyen, Lan Phuong; Cho, Minyeong; Nguyen, Thai Uy; Park, Hee-Kyung; Nguyen, Huong Thi; Mykhailova, Kateryna; Hurh, Sunghoon; Kim, Hong-Rae; Seong, Jae Young; Lee, Cheol Soon; Ham, Byung-Joo; Hwang, Jong-Ik","year":2023,"journal":"Cell & bioscience, 13(1), 212","doi":"10.1186/s13578-023-01165-6","pmid":"37968728","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07225","title":"Ocular Delivery of Therapeutic Agents by Cell-Penetrating Peptides.","authors":"Nhàn, Nguyễn Thị Thanh; Maidana, Daniel E; Yamada, Kaori H","year":2023,"journal":"Cells, 12(7)","doi":"10.3390/cells12071071","pmid":"37048144","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Cell-penetrating peptides can be conjugated with FDA-approved drugs to deliver them to the posterior segment of the eye via topical application, as demonstrated in animal models. This approach could reduce or eliminate the need for frequent intravitreal injections currently required for retinal diseases. The review catalogues various CPP types, their mechanisms of membrane translocation, and emerging peptide-based therapeutics for ocular conditions.","whyItMatters":"Millions of people with retinal diseases like age-related macular degeneration require frequent intravitreal injections — a procedure that is uncomfortable and carries risks including infection and retinal detachment. If CPPs can deliver these same drugs via eye drops, it would transform treatment accessibility, compliance, and safety for patients with chronic eye conditions.","specificNumbers":"","methodology":"This is a systematic review synthesizing literature from PubMed searches and clinical trial databases on cell-penetrating peptides, peptide-based ocular drugs, and CPP-mediated drug delivery systems for eye diseases.","limitations":"As a review, this paper does not present original experimental data. Most CPP ocular delivery evidence comes from animal models, and translation to human eyes — which differ in size and barrier properties — remains to be validated. The review does not provide a quantitative comparison of CPP delivery efficiency versus intravitreal injection, making it difficult to assess how close this technology is to clinical viability."},{"rthcId":"RPEP-07226","title":"Prescription of guideline-directed medical therapies in patients with diabetes and chronic kidney disease from the CURE-CKD Registry, 2019-2020.","authors":"Nicholas, Susanne B; Daratha, Kenn B; Alicic, Radica Z; Jones, Cami R; Kornowske, Lindsey M; Neumiller, Joshua J; Fatoba, Samuel T; Kong, Sheldon X; Singh, Rakesh; Norris, Keith C; Tuttle, Katherine R","year":2023,"journal":"Diabetes, obesity & metabolism, 25(10), 2970-2979","doi":"10.1111/dom.15194","pmid":"37395334","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07227","title":"Peptide Radioligands in Cancer Theranostics: Agonists and Antagonists.","authors":"Nock, Berthold A; Kanellopoulos, Panagiotis; Joosten, Lieke; Mansi, Rosalba; Maina, Theodosia","year":2023,"journal":"Pharmaceuticals (Basel, Switzerland), 16(5)","doi":"10.3390/ph16050674","pmid":"37242457","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07228","title":"Gut hormone co-agonists for the treatment of obesity: from bench to bedside.","authors":"Nogueiras, Ruben; Nauck, Michael A; Tschöp, Matthias H","year":2023,"journal":"Nature metabolism, 5(6), 933-944","doi":"10.1038/s42255-023-00812-z","pmid":"37308724","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07229","title":"Effect of Switching to Once-Weekly Semaglutide on Non-Alcoholic Fatty Liver Disease: The SWITCH-SEMA 1 Subanalysis.","authors":"Nomoto, Hiroshi; Takahashi, Yuka; Takano, Yoshinari; Yokoyama, Hiroki; Tsuchida, Kazuhisa; Nagai, So; Miya, Aika; Kameda, Hiraku; Cho, Kyu Yong; Nakamura, Akinobu; Atsumi, Tatsuya","year":2023,"journal":"Pharmaceutics, 15(8)","doi":"10.3390/pharmaceutics15082163","pmid":"37631377","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07230","title":"Administration of the GLP-1 receptor agonist exenatide in rats improves functional recovery after spinal cord injury by reducing endoplasmic reticulum stress.","authors":"Nomura, Satoshi; Katoh, Hiroyuki; Yanagisawa, Sho; Noguchi, Toshihiro; Okada, Keiko; Watanabe, Masahiko","year":2023,"journal":"IBRO neuroscience reports, 15, 225-234","doi":"10.1016/j.ibneur.2023.09.003","pmid":"37822517","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07231","title":"Safety profile of monoclonal antibodies targeting the calcitonin gene-related peptide system in pregnancy: Updated analysis in VigiBase®.","authors":"Noseda, Roberta; Bedussi, Francesca; Gobbi, Claudio; Ceschi, Alessandro; Zecca, Chiara","year":2023,"journal":"Cephalalgia : an international journal of headache, 43(4), 3331024231158083","doi":"10.1177/03331024231158083","pmid":"36855950","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07232","title":"PDIA3 modulates genomic response to 1,25-dihydroxyvitamin D3 in squamous cell carcinoma of the skin.","authors":"Nowak, Joanna I; Olszewska, Anna M; Piotrowska, Anna; Myszczyński, Kamil; Domżalski, Paweł; Żmijewski, Michał A","year":2023,"journal":"Steroids, 199, 109288","doi":"10.1016/j.steroids.2023.109288","pmid":"37549780","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07233","title":"Bioinformatics procedure for investigating senolytic (anti-aging) agents: A digital signal processing technique.","authors":"Nwankwo, Norbert; Okafor, Ignatius","year":2023,"journal":"Aging medicine (Milton (N.S.W)), 6(4), 338-346","doi":"10.1002/agm2.12274","pmid":"38239718","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The ES2 peptide, which is CR3-based, showed 3–7 times greater senolytic effectiveness than the FOXO4-based DRI peptide. ES2 had higher affinity for the CR3-BDB interaction, which the study identified as crucial for the aging process. The computational analysis confirmed that CR3-based peptides are more potent senolytics overall, consistent with previous experimental findings.","whyItMatters":"Developing effective senolytics could fundamentally change how we treat age-related diseases. This computational approach offers a faster, more systematic way to screen and optimize senolytic peptides before costly lab experiments, potentially accelerating the path to anti-aging therapies.","specificNumbers":"","methodology":"The researchers used the Informational Spectrum Method (ISM), a digital signal processing technique, to computationally analyze the molecular interactions between senolytic peptides and their protein targets. They evaluated the ability of CR3-based and FOXO4-based peptides to disrupt the intermolecular interactions known to drive cellular senescence.","limitations":"This is a purely computational study with no in vitro or in vivo validation of the findings. The digital signal processing method, while consistent with prior experimental data, is a novel technique that has not been widely validated for drug screening. The study does not address bioavailability, toxicity, or practical delivery of these peptides."},{"rthcId":"RPEP-07234","title":"A State of Natriuretic Peptide Deficiency.","authors":"Nyberg, Michael; Terzic, Dijana; Ludvigsen, Trine P; Mark, Peter D; Michaelsen, Natasha B; Abildstrøm, Steen Z; Engelmann, Mads; Richards, A Mark; Goetze, Jens P","year":2023,"journal":"Endocrine reviews, 44(3), 379-392","doi":"10.1210/endrev/bnac029","pmid":"36346821","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A state of partial natriuretic peptide deficiency — characterized by lower plasma NP concentrations — appears to be integral to conditions that precede overt cardiometabolic disease, particularly obesity and type 2 diabetes. Multiple factors affect NP levels: age, sex, race, genetics, and diurnal rhythms. The review highlights that O-glycosylation of NP precursor peptides is highly variable and affects both biomarker measurement accuracy and actual cardiovascular effects. An important proportion of people may have reduced effective NP bioactivity (receptor activation and physiological effects) even when measured peptide levels appear adequate.","whyItMatters":"NPs are already among the most widely used cardiac biomarkers, but this review reframes how we think about them. Instead of only measuring NPs to diagnose heart failure, clinicians could potentially identify people at risk for future cardiometabolic disease by detecting low NP states early. This paradigm shift — from reactive diagnosis to preventive risk assessment — could enable earlier interventions in at-risk populations.","specificNumbers":"","methodology":"Narrative review published in Endocrine Reviews, synthesizing evidence from clinical studies, biomarker research, molecular biology studies of NP biosynthesis, and epidemiological data on NP levels across different populations and disease states.","limitations":"This is a narrative review that proposes a conceptual framework rather than presenting new experimental data. The causal relationship between NP deficiency and cardiometabolic disease development is not definitively established — low NPs could be a consequence rather than a cause. Clinical trials testing NP supplementation or enhancement strategies in at-risk populations have not been completed. The complexity of NP O-glycosylation makes accurate measurement challenging."},{"rthcId":"RPEP-07235","title":"Better Peptides via Chemical Glycosylation: Somatostatin Analogues Having a Human Complex-Type N-Glycan with Improved Drug Properties.","authors":"Ochiai, Hirofumi; Shimoda, Taiji; Fukae, Kazuhiro; Maeda, Masatoshi; Ishii, Kazuyuki; Yoshida, Kenta; Tezuka, Katsunari; Tazuru, Keisuke; Saijo, Hayato; Asai, Hiroaki; Kanatani, Akio; Nishiuchi, Yuji","year":2023,"journal":"Chemistry (Weinheim an der Bergstrasse, Germany), 29(31), e202300111","doi":"10.1002/chem.202300111","pmid":"36945747","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Chemical glycosylation of somatostatin analogs with human complex-type N-glycans (oligosaccharides) achieved two goals simultaneously:\n\n1. Metabolic stability — the glycosylated analogs resisted the rapid plasma degradation that limits native somatostatin's clinical use\n2. Broad receptor affinity — the analogs maintained high binding affinity to all five somatostatin receptor subtypes (sst1-5)\n\nThis is notable because existing somatostatin drugs (like octreotide and lanreotide) sacrifice broad receptor coverage for stability — they are metabolically stable but only bind strongly to sst2 and sst5. The glycosylated analogs achieve both properties. The authors conclude that chemical glycosylation is a powerful general strategy for improving peptide and protein drug candidates.","whyItMatters":"Current somatostatin analogs like octreotide (used for acromegaly, carcinoid tumors, and other conditions) only target a subset of somatostatin receptors. Many diseases involve multiple receptor subtypes, meaning current drugs miss part of the therapeutic effect. A stable analog that activates all five receptors could be more effective for conditions where multiple receptor subtypes contribute — and could open entirely new therapeutic indications. The glycosylation approach could also be applied to improve many other peptide drugs.","specificNumbers":"","methodology":"The researchers synthesized somatostatin analogs and chemically attached human complex-type oligosaccharides (N-glycans) to them. The glycosylated analogs were assessed for metabolic stability (resistance to plasma degradation) and binding affinity to all five somatostatin receptor subtypes (sst1-5). Pharmacokinetic profiles were evaluated to determine improved drug properties compared to native somatostatin.","limitations":"The abstract does not provide specific quantitative data on binding affinities, half-life extension, or pharmacokinetic parameters. No in vivo efficacy studies in disease models are described — only drug property characterization. The complexity of synthesizing glycosylated peptides at scale could be a manufacturing challenge. Whether the broad receptor profile translates to clinical advantages over existing selective analogs remains to be demonstrated. No safety or toxicity data are mentioned."},{"rthcId":"RPEP-07236","title":"Past, Present, and Future of Naturally Occurring Antimicrobials Related to Snake Venoms.","authors":"Oguiura, Nancy; Sanches, Leonardo; Duarte, Priscila V; Sulca-López, Marcos A; Machini, Maria Terêsa","year":2023,"journal":"Animals : an open access journal from MDPI, 13(4)","doi":"10.3390/ani13040744","pmid":"36830531","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07237","title":"Amphiphilic peptide-tagged N-cadherin forms radial glial-like fibers that enhance neuronal migration in injured brain and promote sensorimotor recovery.","authors":"Ohno, Yuya; Nakajima, Chikako; Ajioka, Itsuki; Muraoka, Takahiro; Yaguchi, Atsuya; Fujioka, Teppei; Akimoto, Saori; Matsuo, Misaki; Lotfy, Ahmed; Nakamura, Sayuri; Herranz-Pérez, Vicente; García-Verdugo, José Manuel; Matsukawa, Noriyuki; Kaneko, Naoko; Sawamoto, Kazunobu","year":2023,"journal":"Biomaterials, 294, 122003","doi":"10.1016/j.biomaterials.2023.122003","pmid":"36736095","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07238","title":"Time to Kill and Time to Heal: The Multifaceted Role of Lactoferrin and Lactoferricin in Host Defense.","authors":"Ohradanova-Repic, Anna; Praženicová, Romana; Gebetsberger, Laura; Moskalets, Tetiana; Skrabana, Rostislav; Cehlar, Ondrej; Tajti, Gabor; Stockinger, Hannes; Leksa, Vladimir","year":2023,"journal":"Pharmaceutics, 15(4)","doi":"10.3390/pharmaceutics15041056","pmid":"37111542","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07239","title":"Impact on Knowledge, Competence, and Performance of a Faculty-Led Web-Based Educational Activity for Type 2 Diabetes and Obesity: Questionnaire Study Among Health Care Professionals and Analysis of Anonymized Patient Records.","authors":"Okemah, Jennifer; Neunie, Sola; Noble, Alexander; Wysham, Carol","year":2023,"journal":"JMIR formative research, 7, e49115","doi":"10.2196/49115","pmid":"37703084","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07240","title":"ACE-Inhibitory Activity of Whey Proteins Fractions Derived of Fermentation by Lacticaseibacillus rhamnosus GG and Streptococcus thermophilus SY-102.","authors":"Olvera-Rosales, Laura Berenice; Pérez-Escalante, Emmanuel; Castañeda-Ovando, Araceli; Contreras-López, Elizabeth; Cruz-Guerrero, Alma Elizabeth; Regal-López, Patricia; Cardelle-Cobas, Alejandra; González-Olivares, Luis Guillermo","year":2023,"journal":"Foods (Basel, Switzerland), 12(12)","doi":"10.3390/foods12122416","pmid":"37372627","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Co-culturing L. rhamnosus GG and S. thermophilus SY-102 in whey produced higher protein hydrolysis (453 μg/mL free amino groups), more low molecular weight peptides, and the highest ACE inhibition activity (53.42%) compared to either bacterium alone. The co-culture fermentation extended the logarithmic growth phase to 24 hours, enabling more extensive protein breakdown into bioactive peptides.","whyItMatters":"ACE inhibitors are among the most widely prescribed blood pressure medications. Discovering that probiotic bacteria can generate natural ACE-inhibitory peptides from whey protein during fermentation points toward functional food products that could support cardiovascular health through bioactive peptide delivery.","specificNumbers":"53.42% ACE inhibition · 453 μg/mL free amino groups · 10⁸ CFU/mL initial concentration · co-culture growth phase 24 h · single cultures 6–12 h","methodology":"Whey was fermented using L. rhamnosus GG, S. thermophilus SY-102, or both together, each starting at 10⁸ CFU/mL. Proteolytic profiles were analyzed using TNBS (free amino group quantification), SDS-PAGE (protein size separation), and SEC-HPLC (molecular weight distribution). ACE inhibition capacity was tested using an in vitro assay.","limitations":"ACE inhibition was measured only in vitro — the actual blood pressure-lowering effect of these peptides in humans is unknown. The peptides were not individually identified or characterized. Digestive stability and bioavailability were not assessed. The 53.42% inhibition rate is moderate and may not translate to meaningful clinical effects."},{"rthcId":"RPEP-07241","title":"Inkjet-Based Intracellular Delivery System that Effectively Utilizes Cell-Penetrating Peptides for Cytosolic Introduction of Biomacromolecules through the Cell Membrane.","authors":"Omura, Mika; Morimoto, Kenta; Araki, Yurina; Hirose, Hisaaki; Kawaguchi, Yoshimasa; Kitayama, Yukiya; Goto, Yuto; Harada, Atsushi; Fujii, Ikuo; Takatani-Nakase, Tomoka; Futaki, Shiroh; Nakase, Ikuhiko","year":2023,"journal":"ACS applied materials & interfaces, 15(41), 47855-47865","doi":"10.1021/acsami.3c01650","pmid":"37792057","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07242","title":"Neprilysin-dependent neuropeptide Y cleavage in the liver promotes fibrosis by blocking NPY-receptor 1.","authors":"Ortiz, Cristina; Klein, Sabine; Reul, Winfried H; Magdaleno, Fernando; Gröschl, Stefanie; Dietrich, Peter; Schierwagen, Robert; Uschner, Frank E; Torres, Sandra; Hieber, Christoph; Meier, Caroline; Kraus, Nico; Tyc, Olaf; Brol, Maximilian; Zeuzem, Stefan; Welsch, Christoph; Poglitsch, Marco; Hellerbrand, Claus; Alfonso-Prieto, Mercedes; Mira, Fabio; Keller, Ulrich Auf dem; Tetzner, Anja; Moore, Andrew; Walther, Thomas; Trebicka, Jonel","year":2023,"journal":"Cell reports, 42(2), 112059","doi":"10.1016/j.celrep.2023.112059","pmid":"36729833","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07243","title":"Thymosin beta 4 prevents systemic lipopolysaccharide-induced plaque load in middle-age APP/PS1 mice.","authors":"Othman, Othman; Marshall, Hayley; Masterson, Mitchell; Winlow, Poppy; Gibson, Graham; Ding, Yuchun; Pardon, Marie-Christine","year":2023,"journal":"International immunopharmacology, 117, 109951","doi":"10.1016/j.intimp.2023.109951","pmid":"36878045","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07244","title":"Online large volume sample staking preconcentration and separation of enantiomeric GHRH analogs by capillary electrophoresis.","authors":"Otin, Joanie; Tran, N Thuy; Benoit, Aurélie; Buisson, Corinne; Taverna, Myriam","year":2023,"journal":"Electrophoresis, 44(9-10), 807-817","doi":"10.1002/elps.202200278","pmid":"36787346","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07245","title":"Dermal Hypersensitivity Reaction to Semaglutide: Two Case Reports.","authors":"Ouellette, Samantha; Frias, Giulia; Shah, Radhika; Alamgir, Mahin; Wassef, Cindy","year":2023,"journal":"Journal of drugs in dermatology : JDD, 22(4), 413-416","doi":"10.36849/JDD.6550","pmid":"37026881","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07246","title":"Effect of switching to erenumab in non-responders to a CGRP ligand antibody treatment in migraine: A real-world cohort study.","authors":"Overeem, Lucas Hendrik; Lange, Kristin Sophie; Fitzek, Mira Pauline; Siebert, Anke; Steinicke, Maureen; Triller, Paul; Hong, Ja Bin; Reuter, Uwe; Raffaelli, Bianca","year":2023,"journal":"Frontiers in neurology, 14, 1154420","doi":"10.3389/fneur.2023.1154420","pmid":"37034092","tags":[],"studyType":"retrospective cohort","evidenceStrength":"low","keyFinding":"Among 20 migraine patients who failed CGRP ligand antibodies (galcanezumab or fremanezumab), switching to the CGRP receptor antibody erenumab produced meaningful results: 35% responded at 3 months and 45% responded at 6 months (≥30% reduction in monthly headache days). Monthly headache days decreased from a baseline of 18.6 by 4.1 days at 3 months and 7.0 days at 6 months (both p<0.001). The improving response over time suggests that some patients may need longer than 3 months to benefit from the switch. No demographic or headache characteristics predicted who would respond.","whyItMatters":"When a patient doesn't respond to one anti-CGRP antibody, clinicians face a decision: try a different mechanism (receptor-targeting vs. ligand-targeting) or abandon CGRP therapy entirely. This study — along with data showing the reverse switch also works — demonstrates that the two CGRP antibody classes are not interchangeable, and failure on one doesn't mean failure on the other. The increasing response rate from 35% at 3 months to 45% at 6 months also argues for patience before declaring treatment failure.","specificNumbers":"n=20 · 35% response at 3 months · 45% response at 6 months · -4.1 headache days at 3 months · -7.0 headache days at 6 months · p<0.001 · Baseline: 18.6 headache days/month","methodology":"Retrospective single-center cohort study of patients with episodic or chronic migraine who were non-responders to galcanezumab or fremanezumab (<30% reduction in monthly headache days after 3 months) and subsequently switched to erenumab for at least 3 administrations. Monthly headache days were extracted from headache diaries. Response rates (≥30% reduction) and absolute headache day reductions were assessed at 3 and 6 months.","limitations":"This is a small (n=20), retrospective, single-center study without a control group. The non-response definition (<30% reduction at month 3) may exclude partial responders who might have improved with longer treatment. Only 14 of 20 patients continued to 6 months, introducing potential attrition bias. The study can't distinguish whether improvement was due to the switch versus natural disease fluctuation or regression to the mean. No predictors of response were identified, limiting personalized treatment guidance."},{"rthcId":"RPEP-07247","title":"1,25-Dihydroxyvitamin D3 potentiates the innate immune response of peripheral blood mononuclear cells from Japanese Black cattle.","authors":"Oyamada, Youki; Iizasa, Ei'ichi; Usa, Amane; Otomaru, Konosuke","year":2023,"journal":"Animal science journal = Nihon chikusan Gakkaiho, 94(1), e13906","doi":"10.1111/asj.13906","pmid":"38110290","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07248","title":"Changes in Serum Protein-Peptide Patterns in Atopic Children Allergic to Plant Storage Proteins.","authors":"Packi, Kacper; Matysiak, Joanna; Matuszewska, Eliza; Bręborowicz, Anna; Matysiak, Jan","year":2023,"journal":"International journal of molecular sciences, 24(2)","doi":"10.3390/ijms24021804","pmid":"36675318","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 76 atopic children aged 0-5, sensitization rates to plant storage proteins were: 25% to 2S albumins, 19.7% to 7S globulins, 13.2% to 11S globulins, and 1.3% to cereal prolamins. The most common allergens were peanut proteins: Ara h 1 (18.4%), Ara h 2 (17.1%), Ara h 6 (15.8%), and Ara h 3 (11.8%), with mean sIgE concentrations of 10.93, 15.353, 15.359, and 9.038 kUA/L respectively.\n\nMALDI-TOF mass spectrometry revealed that four proteins were altered in children allergic to storage proteins: cell cycle control protein 50A, testis-expressed sequence 13B, DENN domain-containing protein 5A, and SKI family transcriptional corepressor 2.","whyItMatters":"Plant food allergies in young children are a growing concern, and peanut allergy in particular can be life-threatening. Understanding the molecular signatures in blood that accompany these allergies could lead to better diagnostic tools and earlier identification of at-risk children. The proteomic approach opens a window into the broader biological consequences of food allergy beyond just IgE levels.","specificNumbers":"","methodology":"The study analyzed 76 children aged 0-5 with chronic atopic dermatitis symptoms. Sensitization to 26 plant storage proteins was assessed using the Allergy Explorer ALEX2 multiplex immunoassay. Serum protein-peptide patterns were analyzed using MALDI-TOF mass spectrometry to compare proteomic profiles between children allergic to storage proteins and those who were not.","limitations":"The sample size of 76 children is relatively small for drawing broad conclusions about allergy prevalence. The study was limited to children with atopic dermatitis, who have a higher baseline risk of food allergies. The proteomic findings are exploratory and need validation in larger cohorts. The clinical significance of the four altered proteins is not yet clear."},{"rthcId":"RPEP-07249","title":"Development of Antiplasmodial Peptide-Drug Conjugates Using a Human Protein-Derived Cell-Penetrating Peptide with Selectivity for Infected Cells.","authors":"Palombi, Isabella R; Lawrence, Nicole; White, Andrew M; Gare, Caitlin L; Craik, David J; McMorran, Brendan J; Malins, Lara R","year":2023,"journal":"Bioconjugate chemistry, 34(6), 1105-1113","doi":"10.1021/acs.bioconjchem.3c00147","pmid":"37232456","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07250","title":"Mesoporous silica nanoparticles: An emerging approach in overcoming the challenges with oral delivery of proteins and peptides.","authors":"Pamshong, Sharon Rose; Bhatane, Dhananjay; Sarnaik, Santosh; Alexander, Amit","year":2023,"journal":"Colloids and surfaces. B, Biointerfaces, 232, 113613","doi":"10.1016/j.colsurfb.2023.113613","pmid":"37913702","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Mesoporous silica nanoparticles (MSNs) offer multiple advantages for oral peptide delivery: their pore size and surface can be precisely tailored to load and protect peptides, they have high surface area for drug loading, excellent thermal stability, and good biocompatibility. MSNs can be engineered to respond to specific stimuli (such as pH changes in the gut) to control when and where peptides are released, potentially overcoming the major barriers of enzymatic degradation, poor membrane permeability, and low bioavailability that currently limit oral peptide therapeutics.","whyItMatters":"Most peptide drugs currently require injection, which limits patient compliance and accessibility. If mesoporous silica nanoparticles can successfully protect peptides through the digestive tract and deliver them intact, it could transform how peptide therapies are administered — making them as simple as taking a pill instead of requiring needles.","specificNumbers":"","methodology":"The researchers conducted a comprehensive literature review examining the challenges of oral protein and peptide delivery, strategies to overcome absorption barriers, and the specific role of mesoporous silica nanoparticles as delivery vehicles. They analyzed published studies on MSN design, peptide loading mechanisms, stimuli-responsive release systems, and gene transfection applications.","limitations":"This is a review paper without original experimental data. The authors note that potential risks of mesoporous silica nanoparticles — including long-term toxicity, biodegradation, and organ accumulation — still need to be thoroughly addressed before clinical translation. Most cited studies are preclinical, and oral peptide delivery via MSNs has not yet been validated in human trials."},{"rthcId":"RPEP-07251","title":"Effects of multifaceted optimization management for chronic heart failure: a multicentre, randomized controlled study.","authors":"Pan, Guangming; Ji, Weiqiang; Wang, Xia; Li, Song; Zheng, Chaoyang; Lyu, Weihui; Feng, Xiaoyan; Xia, Yu; Xiong, Zhihua; Shan, Haohong; Yang, Haiyu; Zou, Xu","year":2023,"journal":"ESC heart failure, 10(1), 133-147","doi":"10.1002/ehf2.14170","pmid":"36178015","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07252","title":"Restoration of the Lost Human Beta Defensin (hBD-1) in Cancer as a Strategy to Improve the Efficacy of Chemotherapy.","authors":"Pandurangi, Raghu S; Sekar, Thillai V; Paulmurugan, Ramasamy","year":2023,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2023.04.03.535411","pmid":"37066380","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Human beta defensin-1 (hBD-1) was shown to target the tumor-specific biomarker thioredoxin (Trx) and activate two cell death pathways — CD95 (Fas) and ASK1 (apoptosis stimulating kinase 1) — that are dysregulated in TNBC. Injection of hBD-1 into TNBC mouse models restored the peptide to basal levels and sensitized previously resistant cancer cells to doxorubicin chemotherapy.\n\nThe combination of hBD-1 restoration plus doxorubicin produced significant tumor volume reduction in vivo compared to chemotherapy alone. This represents the first demonstration that injecting hBD-1 can restore its tumor-suppressor function and sensitize TNBC to chemotherapy in a living animal model.","whyItMatters":"TNBC accounts for about 15% of breast cancers and disproportionately affects younger women and Black women. With no targeted therapies available (it lacks the ER, PR, and HER2 receptors that other breast cancers have), patients rely on chemotherapy that often fails due to resistance. If hBD-1 can sensitize these tumors to work at lower chemotherapy doses, it could both improve outcomes and reduce the severe side effects that make TNBC treatment so debilitating.","specificNumbers":"","methodology":"Researchers used TNBC cell lines and mouse tumor models. They first established that hBD-1 expression is lost at high frequency in malignant cancers while maintained in benign tissue. They then injected hBD-1 peptide into TNBC tumors in mice and administered doxorubicin chemotherapy. The study measured activation of CD95 and ASK1 apoptosis pathways, thioredoxin targeting, and tumor volume changes. The approach was termed AAAPT (A priori Activation of Apoptosis Pathways of Tumor).","limitations":"This is a preprint (bioRxiv) that has not undergone peer review, which means the findings have not been independently validated by other scientists. The study used mouse models, and the results may not translate directly to human patients. Specific statistical details, tumor volume measurements, and group sizes are not clearly reported in the abstract. The delivery method (direct tumor injection) is not practical for metastatic disease, and systemic delivery approaches would need to be developed for clinical use."},{"rthcId":"RPEP-07253","title":"Epithelium dynamics differ in time and space when exposed to the permeation enhancers penetramax and EGTA. A head-to-head mechanistic comparison.","authors":"Panou, D A; Pedersen, S F; Kristensen, M; Nielsen, H M","year":2023,"journal":"Frontiers in drug delivery, 3, 1221628","doi":"10.3389/fddev.2023.1221628","pmid":"40838052","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07254","title":"A recombinant approach for stapled peptide discovery yields inhibitors of the RAD51 recombinase.","authors":"Pantelejevs, Teodors; Zuazua-Villar, Pedro; Koczy, Oliwia; Counsell, Andrew J; Walsh, Stephen J; Robertson, Naomi S; Spring, David R; Downs, Jessica A; Hyvönen, Marko","year":2023,"journal":"Chemical science, 14(47), 13915-13923","doi":"10.1039/d3sc03331g","pmid":"38075664","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07255","title":"Enhancing cholangiocarcinoma immunotherapy with adoptive T cells targeting HLA-restricted neoantigen peptides derived from driver gene mutations.","authors":"Panya, Aussara; Thepmalee, Chutamas; Sawasdee, Nunghathai; Saengmuang, Sasithorn; Luangwattananun, Piriya; Yenchitsomanus, Pa-Thai","year":2023,"journal":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 168, 115827","doi":"10.1016/j.biopha.2023.115827","pmid":"37939617","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07256","title":"Radiopharmaceuticals used for diagnosis and therapy of NETs.","authors":"Papachristou, Maria","year":2023,"journal":"Hellenic journal of nuclear medicine, 26 Suppl, 19-20","doi":null,"pmid":"37658556","tags":["somatostatin","cancer"],"studyType":"review","evidenceStrength":"strong","keyFinding":"This review traces the evolution of somatostatin analogue-based radiopharmaceuticals from the first in vivo tumor imaging in 1989 to modern peptide receptor radionuclide therapy (PRRT). Key milestones include: 111In-OctreoScan for SPECT imaging, the shift to PET tracers like 68Ga-DOTATOC and 68Ga-DOTATATE with improved sensitivity, and therapeutic applications using 90Y-DOTATOC and 177Lu-DOTATATE for treating inoperable or metastatic neuroendocrine tumors.\n\nThe newest frontier is targeted alpha-particle therapy (TAT) using actinium-225 (225Ac)-DOTATATE and bismuth-213 (213Bi)-DOTATOC, which showed partial tumor responses without significant toxicity. PRRT side effects are few and mild when kidney protection measures and dose limits are followed. For all approaches, the somatostatin analogue peptide serves as the targeting vehicle that delivers the radioactive payload specifically to tumor cells expressing somatostatin receptors.","whyItMatters":"Neuroendocrine tumors (NETs) are often difficult to treat when they've spread or can't be surgically removed. Somatostatin analogue-based radiopharmaceuticals represent one of the most successful examples of peptide-guided precision medicine — using a peptide to both find tumors (imaging) and kill them (therapy) through the same receptor target. The FDA approval of 177Lu-DOTATATE (Lutathera) in 2018 validated this 'theranostic' approach, and the emergence of alpha-particle emitters like 225Ac-DOTATATE promises even more potent tumor killing with less collateral damage.","specificNumbers":"First imaging: 123I-somatostatin analogue (1989) · 111In-OctreoScan: worldwide adoption · 68Ga-DOTATATE: PET standard · 177Lu-DOTATATE and 90Y-DOTATOC: best therapeutic responses · 225Ac-DOTATATE: partial responses, no significant toxicity · few and mild PRRT side effects with proper precautions","methodology":"Narrative review of the historical development, current state, and future directions of somatostatin analogue radiopharmaceuticals for neuroendocrine tumor diagnosis and therapy. Covers imaging agents (SPECT and PET), therapeutic agents (beta emitters 90Y and 177Lu), and emerging alpha-particle therapies (225Ac and 213Bi).","limitations":"This is a narrative review/conference supplement, not a systematic review or meta-analysis. Specific patient numbers, survival data, and comparative efficacy statistics are not provided in the abstract. The review focuses on somatostatin receptor-positive NETs and may not address the subset of NETs that don't express somatostatin receptors. Long-term data on alpha-particle therapy is limited."},{"rthcId":"RPEP-07257","title":"Double Stranded DNA Binding Stapled Peptides: An Emerging Tool for Transcriptional Regulation.","authors":"Paquette, André R; Boddy, Christopher N","year":2023,"journal":"Chembiochem : a European journal of chemical biology, 24(24), e202300594","doi":"10.1002/cbic.202300594","pmid":"37750576","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review catalogues all known DNA-binding stapled peptides in the literature, noting that despite the strong parallel to protein-protein interaction (PPI) disrupting stapled peptides, very few DNA-binding examples exist. Key observations include:\n\nStapled peptides have proven highly successful at mimicking α-helical protein surfaces to disrupt PPIs, with at least one example in clinical trials. Since DNA-protein interactions are also frequently mediated by α-helices — particularly in transcription factors — the same stapling approach should theoretically apply to DNA binding. Unlike DNA-binding small molecules, which typically lack sequence selectivity, stapled peptides modeled on transcription factor helices could achieve both high affinity and high DNA sequence selectivity.","whyItMatters":"Controlling which genes are active is central to treating cancer, genetic diseases, and many other conditions. Current small molecule approaches to targeting DNA lack the precision to distinguish between similar DNA sequences, leading to off-target effects. If stapled peptides can be designed to bind specific DNA sequences with the same selectivity as natural transcription factors, they could become a powerful new class of therapeutics for diseases driven by aberrant gene expression.","specificNumbers":"","methodology":"This is a review article that comprehensively examines all published examples of DNA-binding stapled peptides. The authors compare the design concepts used in DNA-binding stapled peptides to those established for protein-protein interaction disrupting stapled peptides, identifying trends and design principles from the limited existing literature.","limitations":"As a review, this paper synthesizes existing work rather than presenting new experimental data. The field itself is very young with very few published examples of DNA-binding stapled peptides, making it difficult to draw strong generalizable conclusions. The review does not address practical challenges like cellular delivery, metabolic stability, or in vivo efficacy of DNA-binding stapled peptides. The comparison to PPI-disrupting stapled peptides, while logical, may oversimplify the unique challenges of DNA recognition."},{"rthcId":"RPEP-07258","title":"Exendin-4 affects calcium signalling predominantly during activation and activity of beta cell networks in acute mouse pancreas tissue slices.","authors":"Paradiž Leitgeb, Eva; Kerčmar, Jasmina; Križančić Bombek, Lidija; Pohorec, Vilijem; Skelin Klemen, Maša; Slak Rupnik, Marjan; Gosak, Marko; Dolenšek, Jurij; Stožer, Andraž","year":2023,"journal":"Frontiers in endocrinology, 14, 1315520","doi":"10.3389/fendo.2023.1315520","pmid":"38292770","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07259","title":"Estimation of bioactive peptide content of milk from different species using an in silico method.","authors":"Parastouei, Karim; Jabbari, Masoumeh; Javanmardi, Fardin; Barati, Meisam; Mahmoudi, Yaser; Khalili-Moghadam, Sajad; Ahmadi, Houssein; Davoodi, Sayed Hossein; Mousavi Khaneghah, Amin","year":2023,"journal":"Amino acids, 55(10), 1261-1278","doi":"10.1007/s00726-022-03152-6","pmid":"35306573","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07260","title":"Diagnosis and Treatment of Lung Neuroendocrine Neoplasms: Somatostatin Receptor PET Imaging and Peptide Receptor Radionuclide Therapy.","authors":"Park, Hyesun; Subramaniam, Rathan M","year":2023,"journal":"PET clinics, 18(2), 223-231","doi":"10.1016/j.cpet.2022.11.005","pmid":"36585338","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"68Ga-DOTATATE PET/CT effectively diagnoses lung carcinoids with high somatostatin receptor (SSTR) expression. Combining this with 18F-FDG PET/CT reveals tumor heterogeneity, which is critical for identifying which patients are most likely to benefit from PRRT.\n\nPRRT may serve as an effective and safe treatment for advanced lung carcinoids that progress during first-line somatostatin analog therapy. The theragnostic approach — using the same peptide target for both imaging and treatment — represents a paradigm shift in neuroendocrine tumor management.","whyItMatters":"Lung carcinoids are relatively rare tumors with limited treatment options when they progress on first-line therapy. PRRT represents a targeted approach that uses the tumor's own receptor biology against it — a radioactive peptide binds specifically to somatostatin receptors on the tumor, delivering lethal radiation directly to cancer cells while sparing healthy tissue. The combination of peptide-based imaging and therapy (theragnostics) allows personalized treatment selection.","specificNumbers":"","methodology":"This is a review article summarizing current evidence on somatostatin receptor imaging (68Ga-DOTATATE PET/CT) and peptide receptor radionuclide therapy (PRRT) for lung neuroendocrine neoplasms, with a focus on lung carcinoids.","limitations":"This is a review article, not original research. The abstract does not cite specific response rates, survival data, or trial sizes for PRRT in lung carcinoids. The evidence base for PRRT in lung neuroendocrine tumors is less mature than for gastroenteropancreatic neuroendocrine tumors. PRRT effectiveness depends on sufficient SSTR expression, which varies among lung carcinoid subtypes."},{"rthcId":"RPEP-07261","title":"Glucagon-Like Peptide 1 Analogues as Adjunctive Therapy for Patients With Type 1 Diabetes: An Updated Systematic Review and Meta-analysis.","authors":"Park, Jeayoung; Ntelis, Spyridon; Yunasan, Elvina; Downton, Katherine D; Yip, Terry Cheuk-Fung; Munir, Kashif M; Haq, Nowreen","year":2023,"journal":"The Journal of clinical endocrinology and metabolism, 109(1), 279-292","doi":"10.1210/clinem/dgad471","pmid":"37561012","tags":["glp-1","type-1-diabetes","liraglutide"],"studyType":"systematic-review-meta-analysis","evidenceStrength":"high","keyFinding":"This meta-analysis of 24 randomized controlled trials (3,377 patients) found that GLP-1 analogs — particularly liraglutide — provide meaningful benefits when added to insulin therapy in type 1 diabetes. Liraglutide produced dose-dependent reductions in A1c (-0.09% per mg), body weight (-2.2 kg per mg), and total daily insulin (-4.32 IU per mg).\n\nHowever, higher liraglutide doses came with significantly increased nausea (OR 6.5) and modestly elevated ketosis risk (OR 1.8). Importantly, GLP-1 therapy did not significantly increase severe or symptomatic hypoglycemia. Patients who were newly diagnosed or still producing some insulin (C-peptide positive) showed greater A1c reductions (-0.51% vs -0.28%) but similar weight loss.","whyItMatters":"Type 1 diabetes patients increasingly struggle with obesity, yet they have very few approved add-on therapies beyond insulin. This comprehensive meta-analysis provides the strongest evidence to date that GLP-1 analogs — drugs primarily developed for type 2 diabetes — can meaningfully help type 1 patients lose weight and reduce their insulin doses, though the trade-off includes significant nausea and a small increase in ketosis risk.","specificNumbers":"24 RCTs · 3,377 patients · 4 GLP-1 analogs · A1c: -0.09%/mg liraglutide · Weight: -2.2 kg/mg · TDI: -4.32 IU/mg · Nausea OR 6.5 · Ketosis OR 1.8","methodology":"Systematic review and meta-analysis of randomized controlled trials from PubMed, EMBASE, Cochrane Central, and Scopus through December 2022. Included 24 studies testing 4 different GLP-1 analogs in type 1 diabetes patients for at least 12 weeks. Assessed efficacy (A1c, weight, insulin dose) and 12 adverse outcomes. Used GRADE framework for evidence certainty.","limitations":"Most evidence comes from liraglutide studies, so findings for other GLP-1 analogs (exenatide, etc.) are less robust. Studies of exenatide had higher risk of bias and sparse safety data. No GLP-1 analog is currently FDA-approved for type 1 diabetes, so all use remains off-label. The meta-analysis could not assess very long-term outcomes beyond typical trial durations."},{"rthcId":"RPEP-07262","title":"Low-Molecular Collagen Peptide Supplementation and Body Fat Mass in Adults Aged ≥ 50 Years: A Randomized, Double-Blind, Placebo-Controlled Trial.","authors":"Park, Jeongbin; Kim, Minji; Shin, Hyeri; Ahn, Hyejin; Park, Yoo Kyoung","year":2023,"journal":"Clinical nutrition research, 12(4), 245-256","doi":"10.7762/cnr.2023.12.4.245","pmid":"37969940","tags":["collagen-peptides","body-composition"],"studyType":"randomized-controlled-trial","evidenceStrength":"moderate","keyFinding":"Older adults (≥50 years) who took 15 grams of low-molecular collagen peptides daily for 12 weeks experienced a significant reduction in body fat mass compared to placebo, confirmed by two independent measurement methods (BIA and DEXA).\n\nThe collagen group saw a -0.49% change in total fat mass while the placebo group gained 2.23% (p=0.041). Within the collagen group, significant reductions were observed in whole body fat mass (p=0.002), whole body fat percentage (p=0.002), trunk fat mass (p=0.001), and trunk fat percentage (p<0.001). Importantly, physical activity levels, dietary intake, and blood biochemistry did not differ between groups, suggesting the effect was from the collagen supplementation itself.","whyItMatters":"Age-related fat gain — especially around the trunk — is a major health concern for older adults, contributing to cardiovascular disease, diabetes, and mobility issues. If collagen peptide supplementation can meaningfully reduce body fat without requiring changes to diet or exercise, it would represent a simple, accessible intervention. This trial adds to growing evidence that collagen peptides may have metabolic effects beyond their well-known benefits for skin and joints.","specificNumbers":"n=74 · 12 weeks · 15 g/day collagen peptides · Fat mass change: -0.49% vs +2.23% (p=0.041) · BIA p=0.021 · DEXA p=0.041 · Whole body fat mass p=0.002 · Trunk fat mass p=0.001","methodology":"Randomized, double-blind, placebo-controlled trial with 74 adults aged 50 and older. Participants were assigned to receive either 15 g/day of low-molecular collagen peptide or a placebo drink for 12 weeks while maintaining their normal physical activity levels. Body composition was measured using both bioelectrical impedance analysis (BIA) and dual-energy X-ray absorptiometry (DEXA). Physical activity, dietary intake, and blood biochemical markers were also monitored.","limitations":"The sample size of 74 is relatively small. The 12-week duration doesn't reveal whether fat loss continues, plateaus, or reverses after stopping supplementation. The specific mechanism by which collagen peptides reduce body fat is not explained. BIA can be influenced by hydration status. Published in a smaller journal (Clinical Nutrition Research) rather than a high-impact journal. The collagen peptide product specifics (brand, amino acid profile) may affect reproducibility."},{"rthcId":"RPEP-07263","title":"Tales from the life and lab of a female social neuroscientist.","authors":"Parker, Karen J","year":2023,"journal":"Comprehensive psychoneuroendocrinology, 16, 100202","doi":"10.1016/j.cpnec.2023.100202","pmid":"38108026","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07264","title":"Insight into the Mechanism of Interactions between the LL-37 Peptide and Model Membranes of Legionella gormanii Bacteria.","authors":"Pastuszak, Katarzyna; Kowalczyk, Bozena; Tarasiuk, Jacek; Luchowski, Rafal; Gruszecki, Wieslaw I; Jurak, Małgorzata; Palusinska-Szysz, Marta","year":2023,"journal":"International journal of molecular sciences, 24(15)","doi":"10.3390/ijms241512039","pmid":"37569419","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07265","title":"Exercise Training, Cardiac Biomarkers, and Cardiorespiratory Fitness in Type 2 Diabetes: The HART-D Study.","authors":"Patel, Kershaw V; Saha, Amit; Ayers, Colby R; Rohatgi, Anand; Berry, Jarett D; Almandoz, Jaime P; Johannsen, Neil M; deFilippi, Christopher; Church, Timothy S; de Lemos, James A; Pandey, Ambarish","year":2023,"journal":"JACC. Advances, 2(1), 100174","doi":"10.1016/j.jacadv.2022.100174","pmid":"38939024","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07266","title":"Relationship between body weight change and glycaemic control with tirzepatide treatment in people with type 2 diabetes: A post hoc assessment of the SURPASS clinical trial programme.","authors":"Pedersen, Sue D; Giorgino, Francesco; Umpierrez, Guillermo; Thieu, Vivian T; Rodríguez, Angel; Nicolay, Claudia; Fernández Landó, Laura; Karanikas, Chrisanthi A; Kiljanski, Jacek","year":2023,"journal":"Diabetes, obesity & metabolism, 25(9), 2553-2560","doi":"10.1111/dom.15140","pmid":"37246796","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07267","title":"Molecular hybridization strategy for tuning bioactive peptide function.","authors":"Pedron, Cibele Nicolaski; Torres, Marcelo Der Torossian; Oliveira, Cyntia Silva; Silva, Adriana Farias; Andrade, Gislaine Patricia; Wang, Yiming; Pinhal, Maria Aparecida Silva; Cerchiaro, Giselle; da Silva Junior, Pedro Ismael; da Silva, Fernanda Dias; Radhakrishnan, Ravi; de la Fuente-Nunez, Cesar; Oliveira Junior, Vani Xavier","year":2023,"journal":"Communications biology, 6(1), 1067","doi":"10.1038/s42003-023-05254-7","pmid":"37857855","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07268","title":"Equine β-defensin 1 regulates cytokine expression and phagocytosis in S. aureus-infected mouse monocyte macrophages via the Paxillin-FAK-PI3K pathway.","authors":"Pei, Le; Hou, Yongyue; Feng, Ying; Li, Feng; Su, Hong; Zhang, Yuemei; Song, Yue; Liu, Kun; Cao, Guifang","year":2023,"journal":"International immunopharmacology, 123, 110793","doi":"10.1016/j.intimp.2023.110793","pmid":"37582311","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07269","title":"Brain-Penetrating Peptide Shuttles across the Blood-Brain Barrier and Extracellular-like Space.","authors":"Peng, Xiujuan; Liu, Xinquan; Kim, Jae You; Nguyen, Alex; Leal, Jasmim; Ghosh, Debadyuti","year":2023,"journal":"Bioconjugate chemistry, 34(12), 2319-2336","doi":"10.1021/acs.bioconjchem.3c00446","pmid":"38085066","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07270","title":"Toward a consensus nomenclature for ghrelin, its non-acylated form, liver expressed antimicrobial peptide 2 and growth hormone secretagogue receptor.","authors":"Perelló, Mario; Dickson, Suzanne L; Zigman, Jeffrey M; Leggio, Lorenzo","year":2023,"journal":"Journal of neuroendocrinology, 35(1), e13224","doi":"10.1111/jne.13224","pmid":"36580314","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"An expert consensus survey established standardized nomenclature for the ghrelin system: 'ghrelin' (the octanoylated active peptide), 'desacyl-ghrelin' (the non-acylated form that does not bind GHSR at physiological levels), 'GHSR' (growth hormone secretagogue receptor), and 'LEAP2' (liver-expressed antimicrobial peptide 2, a recently recognized endogenous GHSR antagonist/inverse agonist).\n\nThe paper also contextualizes that ghrelin controls not only growth hormone secretion but also food intake, reward-related behaviors, glucose homeostasis, and gastrointestinal motility. Desacyl-ghrelin's physiological role remains less well-characterized despite being detectable in biological samples.","whyItMatters":"Inconsistent terminology in scientific literature creates confusion and miscommunication, particularly for researchers entering the field or clinicians reading about ghrelin-based therapies. Standardized nomenclature is essential as ghrelin system research advances toward clinical applications — including potential treatments for eating disorders, obesity, cachexia, and addiction. The identification of LEAP2 as an endogenous ghrelin blocker also opens new therapeutic avenues.","specificNumbers":"","methodology":"The authors conducted a survey among experts who have contributed to the ghrelin literature, aiming to identify whether consensus could be reached on nomenclature for ghrelin, its non-acylated form, its receptor, and its endogenous antagonist. The consensus recommendations were based on survey results from the research community.","limitations":"This is primarily a nomenclature consensus paper, not a study presenting new experimental data. The survey was limited to researchers already publishing in the ghrelin field, which may not capture perspectives from adjacent fields. Desacyl-ghrelin's physiological role remains unresolved, and the consensus on naming it doesn't address the ongoing debate about whether it has biological activity independent of GHSR."},{"rthcId":"RPEP-07271","title":"Bioactive peptides from scorpion venoms: therapeutic scaffolds and pharmacological tools.","authors":"Peter Muiruri, Kamau; Zhong, Jian; Yao, Bing; Lai, Ren; Luo, Lei","year":2023,"journal":"Chinese journal of natural medicines, 21(1), 19-35","doi":"10.1016/S1875-5364(23)60382-6","pmid":"36641229","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07272","title":"Structure-Activity Relationships of Bis-Intercalating Peptides and Their Application as Antibody-Drug Conjugate Payloads.","authors":"Petersen, Mark E; Brant, Michael G; Lasalle, Manuel; Fung, Vincent K C; Rojas, Andrea Hernandez; Wong, Jodi; Das, Samir; Barnscher, Stuart D; Rich, Jamie R; Winters, Geoffrey C","year":2023,"journal":"Journal of medicinal chemistry, 66(12), 8288-8309","doi":"10.1021/acs.jmedchem.3c00760","pmid":"37307297","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"34 novel synthetic analogs of DNA bis-intercalating peptides were synthesized and characterized. Initial ADC constructs were hydrophobic and aggregation-prone. Two strategies improved properties: solubilizing linker groups and enzymatically cleavable hydrophilic masks. All ADCs showed potent in vitro cytotoxicity in high-antigen-expressing cells. Masked ADCs were less potent in low-antigen cell lines. In vivo, stochastically conjugated DAR4 anti-FRα ADCs were toxic at low doses, while site-specific THIOMAB DAR2 anti-cMet ADCs were well-tolerated and highly efficacious — demonstrating that conjugation strategy critically affects the therapeutic window.","whyItMatters":"ADCs are among the fastest-growing class of cancer drugs, with over a dozen approved. Finding new, potent payloads is critical because current options (auristatins, maytansinoids) face resistance in some tumors. DNA-intercalating peptides represent a mechanistically distinct payload class that kills cells differently — by disrupting DNA structure directly. The optimization work on conjugation chemistry and masking strategies addresses the key practical challenges of making peptide-based payloads clinically viable.","specificNumbers":"","methodology":"Researchers synthesized 34 analogs of sandramycin and quinaldopeptin-based bis-intercalating peptides using medicinal chemistry approaches. Biophysical characterization assessed DNA binding and physicochemical properties. In vitro cytotoxicity was tested across cancer cell lines with varying antigen expression. Drug-linker chemistry was optimized using solubilizing groups and cleavable masks. Two in vivo pilot studies compared stochastic (DAR4) versus site-specific (THIOMAB DAR2) conjugation strategies.","limitations":"Only two pilot in vivo studies were conducted, providing preliminary efficacy and tolerability data. The DAR4 anti-FRα ADC showed dose-limiting toxicity even at low doses, indicating a narrow therapeutic window for some configurations. Masked ADCs showed reduced potency in low-antigen cell lines, which could limit their use in heterogeneous tumors. Long-term efficacy, pharmacokinetics, and safety profiles were not characterized. No clinical data exist."},{"rthcId":"RPEP-07273","title":"Insight into the self-assembly and gel formation of a bioactive peptide derived from bovine casein.","authors":"Petit, Noémie; Dyer, Jolon M; Gerrard, Juliet A; Domigan, Laura J; Clerens, Stefan","year":2023,"journal":"BBA advances, 3, 100086","doi":"10.1016/j.bbadva.2023.100086","pmid":"37378356","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07274","title":"The mitochondrially targeted peptide elamipretide (SS-31) improves ADP sensitivity in aged mitochondria by increasing uptake through the adenine nucleotide translocator (ANT).","authors":"Pharaoh, Gavin; Kamat, Varun; Kannan, Sricharan; Stuppard, Rudolph S; Whitson, Jeremy; Martín-Pérez, Miguel; Qian, Wei-Jun; MacCoss, Michael J; Villén, Judit; Rabinovitch, Peter; Campbell, Matthew D; Sweet, Ian R; Marcinek, David J","year":2023,"journal":"GeroScience, 45(6), 3529-3548","doi":"10.1007/s11357-023-00861-y","pmid":"37462785","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07275","title":"Avian opioid peptides: evolutionary considerations, functional roles and a challenge to address critical questions.","authors":"Pierzchała-Koziec, Krystyna; Scanes, Colin G","year":2023,"journal":"Frontiers in physiology, 14, 1164031","doi":"10.3389/fphys.2023.1164031","pmid":"37346481","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07276","title":"Cell starvation increases uptake of extracellular Thymosin β4 and its complexes with calcium.","authors":"Piludu, Marco; Pichiri, Giuseppina; Coni, Pierpaolo; Piras, Monica; Congiu, Terenzio; Faa, Gavino; Lachowicz, Joanna Izabela","year":2023,"journal":"International immunopharmacology, 116, 109743","doi":"10.1016/j.intimp.2023.109743","pmid":"36706591","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Under normal growth conditions, intracellular free calcium and Thymosin β4 concentrations are strictly regulated and unaffected by extracellular supplementation. However, cell starvation decreases intracellular Thymosin β4 levels and increases uptake of extracellular peptide above the normal range. Most significantly, cell starvation dramatically increases internalization of extracellular Ca2+/Thymosin β4 complexes, suggesting a starvation-triggered mechanism that could be relevant to the early stages of cancer metastasis.","whyItMatters":"Metastasis — cancer spreading to other organs — is the primary cause of cancer death. Understanding the earliest steps of how cancer cells begin to move is critical for developing therapies to prevent spread. This study reveals that Thymosin β4, a peptide already linked to tumor metastasis and cell migration, has a previously unknown calcium-dependent uptake mechanism that's activated under starvation conditions typical of tumor microenvironments.","specificNumbers":"","methodology":"In vitro cell culture study examining Thymosin β4 and calcium dynamics under normal and starvation conditions. Researchers measured intracellular Thymosin β4 concentrations, tracked uptake of extracellular Thymosin β4 and Ca2+/Thymosin β4 complexes, and compared responses between well-fed and starved cells.","limitations":"This is an in vitro cell culture study that may not fully replicate the complex tumor microenvironment. The specific cell types used and starvation protocols could influence results. The study identifies a mechanism but does not demonstrate its role in actual metastasis in vivo. The connection between increased Thymosin β4/calcium uptake and functional cell migration or invasion was not directly tested."},{"rthcId":"RPEP-07277","title":"Immunosuppressive, antimicrobial and insecticidal activities of inhibitor cystine knot peptides produced by teratocytes of the endoparasitoid wasp Cotesia flavipes (Hymenoptera: Braconidae).","authors":"Pinto, Ciro P G; Walker, Andrew A; King, Glenn F; Rossi, Guilherme D","year":2023,"journal":"Insect science, 30(4), 1105-1117","doi":"10.1111/1744-7917.13154","pmid":"36434808","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07278","title":"Cytomegalovirus seropositivity correlates with both human β-defensin 1 and IFN-γ downregulation in women with obesity.","authors":"Pita López, María Luisa; Ruiz Ramírez, Andrea Virginia; Alcázar Ríos, José Alberto; Santos Hernández, Carmen; Guerrero Velázquez, Celia; Prado Montes de Oca, Ernesto","year":2023,"journal":"Cytokine, 168, 156230","doi":"10.1016/j.cyto.2023.156230","pmid":"37235888","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07279","title":"G protein-coupled receptors and obesity.","authors":"Pocai, Alessandro","year":2023,"journal":"Frontiers in endocrinology, 14, 1301017","doi":"10.3389/fendo.2023.1301017","pmid":"38161982","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies several major developments in GPCR-targeted obesity therapeutics:\n\n1. Semaglutide established the benchmark as the first peptide GLP-1 receptor agonist achieving ≥10% weight loss with cardiovascular benefits (MACE reduction)\n2. Dual GLP-1/GIP agonists (like tirzepatide) demonstrate enhanced weight loss over single-target GLP-1 drugs\n3. Triple agonists targeting GLP-1, GIP, and glucagon receptors simultaneously are in development for even greater efficacy\n4. Oral formulations are advancing, including oral semaglutide tablets and small molecule non-peptide GLP-1 receptor agonists\n5. Fixed-dose combinations and add-on therapies are being developed for patients who need weight loss beyond what single-agent GLP-1 therapy provides","whyItMatters":"Obesity is a chronic disease affecting over 650 million adults globally, with devastating consequences including diabetes, heart disease, and cancer. The success of semaglutide proved that pharmacological weight management can achieve meaningful clinical outcomes. This review captures a pivotal moment — the transformation of obesity treatment from a neglected field to one of the most active areas of drug development, with multiple competing approaches targeting different combinations of incretin receptors.","specificNumbers":"","methodology":"Narrative review published in Frontiers in Endocrinology, surveying the current state and emerging pipeline of GPCR-targeted anti-obesity medications. Covers approved drugs, clinical-stage candidates, and preclinical approaches across multiple receptor targets.","limitations":"As a narrative review, this paper provides an overview without systematic methodology. Published in 2023, some developments (particularly clinical trial results for newer agents) may have advanced since publication. The review focuses primarily on GPCR targets and may not fully cover non-GPCR approaches to obesity (like amylin analogs or central-acting agents). Commercial opportunity discussions may reflect industry perspective."},{"rthcId":"RPEP-07280","title":"Emerging Role of GLP-1 Agonists in Obesity: A Comprehensive Review of Randomised Controlled Trials.","authors":"Popoviciu, Mihaela-Simona; Păduraru, Lorena; Yahya, Galal; Metwally, Kamel; Cavalu, Simona","year":2023,"journal":"International journal of molecular sciences, 24(13)","doi":"10.3390/ijms241310449","pmid":"37445623","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07281","title":"A Single Surface-Exposed Amino Acid Determines Differential Neutralization of AAV1 and AAV6 by Human Alpha-Defensins.","authors":"Porter, Jessica M; Oswald, Mackenzi S; Sharma, Anjali; Emmanuel, Shanan; Kansol, Austin; Bennett, Antonette; McKenna, Robert; Smith, Jason G","year":2023,"journal":"Journal of virology, 97(3), e0006023","doi":"10.1128/jvi.00060-23","pmid":"36916912","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07282","title":"Diversity of the Antimicrobial Peptide Genes in Collembola.","authors":"Pradhan, Goma; Engsontia, Patamarerk","year":2023,"journal":"Insects, 14(3)","doi":"10.3390/insects14030215","pmid":"36975900","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07283","title":"Structural characteristic and molecular docking simulation of fish protein-derived peptides: Recent updates on antioxidant, anti-hypertensive and anti-diabetic peptides.","authors":"Prakash Nirmal, Nilesh; Singh Rajput, Mithun; Bhojraj Rathod, Nikheel; Mudgil, Priti; Pati, Siddhartha; Bono, Gioacchino; Nalinanon, Sitthipong; Li, Li; Maqsood, Sajid","year":2023,"journal":"Food chemistry, 405(Pt A), 134737","doi":"10.1016/j.foodchem.2022.134737","pmid":"36335734","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07284","title":"Orforglipron (LY3502970), a novel, oral non-peptide glucagon-like peptide-1 receptor agonist: A Phase 1a, blinded, placebo-controlled, randomized, single- and multiple-ascending-dose study in healthy participants.","authors":"Pratt, Edward; Ma, Xiaosu; Liu, Rong; Robins, Deborah; Haupt, Axel; Coskun, Tamer; Sloop, Kyle W; Benson, Charles","year":2023,"journal":"Diabetes, obesity & metabolism, 25(9), 2634-2641","doi":"10.1111/dom.15184","pmid":"37344954","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In Part A (single dose, n=32), orforglipron showed dose-proportional pharmacokinetics with a half-life of 24.6–35.3 hours across doses of 0.3–6 mg. In Part B (multiple dose, n=60), 4 weeks of daily dosing with escalation to final target doses of 2–24 mg resulted in extended half-lives of 48.1–67.5 hours.\n\nParticipants receiving orforglipron lost up to 5.4 kg of body weight after 4 weeks compared to 2.4 kg with placebo (P < 0.05). Fasting glucose levels decreased across the treatment period, and gastric emptying was delayed on Day 28 — all consistent with GLP-1 receptor activation. The most common adverse events were gastrointestinal, similar to injectable GLP-1 receptor agonists.","whyItMatters":"Current GLP-1 receptor agonists for weight loss and diabetes require injection, which limits adoption. An oral non-peptide alternative that works similarly could dramatically expand access to these treatments. Orforglipron's once-daily dosing without food or water restrictions also improves on existing oral GLP-1 options like oral semaglutide, which requires fasting.","specificNumbers":"","methodology":"This was a Phase 1, double-blind, placebo-controlled, randomized study in healthy adults aged 18–65 with BMI 20–40 kg/m² and HbA1c below 6.5%. Part A tested single escalating doses (0.3–6 mg) in four cohorts. Part B tested 4 weeks of daily dosing with weekly dose escalation to four final target doses (2–24 mg). Safety, pharmacokinetics, body weight, fasting glucose, and gastric emptying were assessed.","limitations":"This was a Phase 1 study in healthy participants, not patients with diabetes or obesity. The treatment period was only 4 weeks, too short to assess long-term efficacy or safety. The sample size was small (92 total, split across multiple dose groups). Efficacy endpoints were exploratory, and larger Phase 2/3 trials in target patient populations are needed."},{"rthcId":"RPEP-07285","title":"Orforglipron (LY3502970), a novel, oral non-peptide glucagon-like peptide-1 receptor agonist: A Phase 1b, multicentre, blinded, placebo-controlled, randomized, multiple-ascending-dose study in people with type 2 diabetes.","authors":"Pratt, Edward; Ma, Xiaosu; Liu, Rong; Robins, Deborah; Coskun, Tamer; Sloop, Kyle W; Haupt, Axel; Benson, Charles","year":2023,"journal":"Diabetes, obesity & metabolism, 25(9), 2642-2649","doi":"10.1111/dom.15150","pmid":"37264711","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across multiple dosing regimens over 12 weeks, orforglipron produced mean HbA1c reductions of 1.5% to 1.8%, compared to 0.4% with placebo. Body weight changes ranged from -0.24 kg to -5.8 kg with orforglipron, versus +0.5 kg with placebo.\n\nThe drug had a half-life of 29-49 hours at Week 12, supporting once-daily dosing. Weekly dose escalation was shown to be generally well tolerated, providing guidance for future dosing protocols.\n\nThe most common adverse events were gastrointestinal-related and occurred early in treatment, consistent with the known class effects of GLP-1 receptor agonists. No new safety signals were identified beyond what is expected for this drug class.","whyItMatters":"All currently available GLP-1 receptor agonists are peptide-based, requiring either injection or special oral formulations with strict fasting rules. Orforglipron represents a potential paradigm shift — a simple daily pill that activates the GLP-1 receptor without being a peptide. If confirmed in larger trials, this could dramatically expand access to GLP-1 therapy for the hundreds of millions of people with type 2 diabetes worldwide who prefer oral medications over injections.","specificNumbers":"","methodology":"This was a Phase 1b, multicentre, double-blind, placebo-controlled, randomized, multiple-ascending-dose study. Five different dosing regimens were tested: the first group established tolerability with weekly dose escalation, followed by four parallel-arm groups. Participants (ages 18-70, HbA1c 7.0-10.5%) were randomized 3:1 to orforglipron or placebo for 12 weeks. Endpoints included safety, pharmacokinetics, HbA1c change, and body weight change.","limitations":"This is a small Phase 1b study (68 participants) primarily designed for safety and pharmacokinetic assessment, not powered for definitive efficacy conclusions. The 12-week duration is short for assessing long-term metabolic outcomes and safety. The wide range in weight loss (-0.24 to -5.8 kg) across doses suggests dose-response optimization is still needed. No direct comparisons to injectable GLP-1 agonists were included. Long-term cardiovascular and renal outcomes are unknown."},{"rthcId":"RPEP-07286","title":"The Predictive Value of A, B, and C-Type Natriuretic Peptides in People at Risk of Heart Disease: Protocol for a Longitudinal Observational Study.","authors":"Prickett, Timothy C R; Pearson, John F; Troughton, Richard W; Kennedy, Martin A; Espiner, Eric A","year":2023,"journal":"JMIR research protocols, 12, e37011","doi":"10.2196/37011","pmid":"36630163","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07287","title":"Resveratrol-Induced Suppression of C-type Natriuretic Peptide Associates With Increased Vertebral Bone Density in Postmenopausal Women.","authors":"Prickett, Timothy Cr; Howe, Peter Rc; Espiner, Eric A","year":2023,"journal":"JBMR plus, 7(5), e10732","doi":"10.1002/jbm4.10732","pmid":"37197320","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07288","title":"Effects of dulaglutide on alcohol consumption during smoking cessation.","authors":"Probst, Leila; Monnerat, Sophie; Vogt, Deborah R; Lengsfeld, Sophia; Burkard, Thilo; Meienberg, Andrea; Bathelt, Cemile; Christ-Crain, Mirjam; Winzeler, Bettina","year":2023,"journal":"JCI insight, 8(22)","doi":"10.1172/jci.insight.170419","pmid":"37991022","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07289","title":"Outcome analysis in patients with metastatic gastroenteropancreatic neuroendocrine tumors receiving peptide receptor radionuclide therapy with Lu-177-DOTATATE.","authors":"Prétot, Dominique; Engel-Bicik, Ivette; Kenkel, David; Kaufmann, Philipp A; Treyer, Valerie; Siebenhüner, Alexander R","year":2023,"journal":"Journal of gastrointestinal oncology, 14(3), 1204-1217","doi":"10.21037/jgo-22-874","pmid":"37435198","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07290","title":"Identification of Bioactive Peptides from a Laminaria digitata Protein Hydrolysate Using In Silico and In Vitro Methods to Identify Angiotensin-1-Converting Enzyme (ACE-1) Inhibitory Peptides.","authors":"Purcell, Diane; Packer, Michael A; Hayes, Maria","year":2023,"journal":"Marine drugs, 21(2)","doi":"10.3390/md21020090","pmid":"36827131","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07291","title":"Bioactive Suture with Added Innate Defense Functionality for the Reduction of Bacterial Infection and Inflammation.","authors":"Puthia, Manoj; Petrlova, Jitka; Petruk, Ganna; Butrym, Marta; Samsudin, Firdaus; Andersson, Madelene Å; Strömdahl, Ann-Charlotte; Wasserstrom, Sebastian; Hartman, Erik; Kjellström, Sven; Caselli, Lucrezia; Klementieva, Oxana; Bond, Peter J; Malmsten, Martin; Raina, Deepak Bushan; Schmidtchen, Artur","year":2023,"journal":"Advanced healthcare materials, 12(31), e2300987","doi":"10.1002/adhm.202300987","pmid":"37689972","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07292","title":"Recognition of the interaction between the bioactive peptide Val-Pro-Pro and the minimal promoter region of genes SOD and CAT using QCM-D and docking studies.","authors":"Pérez-Vielma, Nadia Mabel; Gómez-López, Modesto; Maldonado, Jesús; Correa-Basurto, José; Martínez-Godínez, María de Los Ángeles; Miliar-García, Ángel","year":2023,"journal":"Analytical methods : advancing methods and applications, 15(24), 2979-2988","doi":"10.1039/d3ay00265a","pmid":"37309667","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07293","title":"Efficacy and safety profile of Glucagon-Like Peptide-1 Receptor Agonist in obese Type-2 diabetes patients from a private institution in Karachi.","authors":"Qasim, Saeeda Fouzia; Ahsan, Tasnim; Ghaus, Saima; Imran, Paras","year":2023,"journal":"Pakistan journal of medical sciences, 39(4), 1113-1118","doi":"10.12669/pjms.39.4.7353","pmid":"37492314","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07294","title":"Agrp-negative arcuate NPY neurons drive feeding under positive energy balance via altering leptin responsiveness in POMC neurons.","authors":"Qi, Yue; Lee, Nicola J; Ip, Chi Kin; Enriquez, Ronaldo; Tasan, Ramon; Zhang, Lei; Herzog, Herbert","year":2023,"journal":"Cell metabolism, 35(6), 979-995.e7","doi":"10.1016/j.cmet.2023.04.020","pmid":"37201523","tags":["neuropeptides","obesity-and-metabolism","appetite-regulation"],"studyType":"animal","evidenceStrength":"strong","keyFinding":"The researchers identified a previously unknown population of AgRP-negative NPY neurons in the arcuate nucleus of the hypothalamus. Under positive energy balance (high-fat diet or genetic obesity), NPY2 receptor expression increases specifically on POMC neurons — the cells that normally signal fullness.\n\nThis upregulation allows NPY released from the newly discovered AgRP-negative neurons to override POMC satiety signaling and alter leptin responsiveness. When the researchers artificially activated this circuit using chemogenetics, mice ate significantly more. When they inhibited it with optogenetics, feeding decreased. Mice lacking NPY2 receptors on their POMC neurons ate less and had lower body fat.","whyItMatters":"Obesity research has long struggled to explain why the brain keeps promoting food intake even when the body clearly has excess energy stored as fat. This study reveals a specific neural mechanism: a subset of NPY neurons that bypasses normal satiety controls by targeting high-affinity receptors that remain responsive even when overall NPY levels drop. This circuit could be a future drug target for obesity treatment — blocking NPY2R on POMC neurons might help restore normal appetite regulation in people with obesity.","specificNumbers":"NPY2R upregulated on POMC neurons during HFD; chemogenetic activation strongly drives feeding; optogenetic inhibition reduces feeding; Npy2r knockout on POMC neurons reduces food intake and fat mass","methodology":"This was a mouse neuroscience study using multiple advanced techniques. The team fed mice a high-fat diet or used genetically obese mice lacking leptin receptors. They mapped neural circuits to identify AgRP-negative NPY neurons projecting to POMC neurons. They used chemogenetics (DREADDs) to activate the circuit and optogenetics to inhibit it, measuring food intake in both cases. They also created mice with NPY2 receptors genetically removed from POMC neurons to test the receptor's role in feeding and fat accumulation.","limitations":"This is entirely a mouse study, and the specific neural circuits identified may not map identically to the human brain. The chemogenetic and optogenetic tools used provide artificial stimulation that may not perfectly mimic natural neural activity. The study focused on circuit identification and proof-of-concept rather than therapeutic development, and long-term metabolic outcomes were not detailed in the abstract."},{"rthcId":"RPEP-07295","title":"Recent advances in the tumor-penetrating peptide internalizing RGD for cancer treatment and diagnosis.","authors":"Qian, Jing; Zhou, Sheng; Lin, Peng; Lei, Jin; Zheng, Shiqi; Xu, Wenmang; Wang, Yuanyuan; Gao, Ziran; Yang, Julun","year":2023,"journal":"Drug development research, 84(4), 654-670","doi":"10.1002/ddr.22056","pmid":"36959702","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07296","title":"Multi-omic and comparative analyses revealed monocyte-derived alpha-defensin-1 correlated with COVID-19 severity and inhibited SARS-CoV-2 infection.","authors":"Qian, Xijing; Wu, Bingan; Chen, Xiang; Peng, Haoran; Liu, Miao; Tang, Hailin; Xu, Zhengmei; Xu, Chen; Qi, Zhongtian","year":2023,"journal":"Journal of medical virology, 95(6), e28845","doi":"10.1002/jmv.28845","pmid":"37254949","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07297","title":"Characterization of hepcidin gene and protection of recombinant hepcidin supplemented in feed against Aeromonas hydrophila infection in Yellow River carp (Cyprinus carpio haematopterus).","authors":"Qiao, Dan; Yan, Yan; Pei, Chao; Zhang, Jinghang; Zhao, Xianliang; Jiang, Xinyu; Zhu, Lei; Zhang, Jie; Li, Li; Kong, Xianghui","year":2023,"journal":"Fish & shellfish immunology, 139, 108872","doi":"10.1016/j.fsi.2023.108872","pmid":"37271324","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07298","title":"Antiviral Activity against SARS-CoV-2 of Conformationally Constrained Helical Peptides Derived from Angiotensin-Converting Enzyme 2.","authors":"Quagliata, Michael; Stincarelli, Maria Alfreda; Papini, Anna Maria; Giannecchini, Simone; Rovero, Paolo","year":2023,"journal":"ACS omega, 8(25), 22665-22672","doi":"10.1021/acsomega.3c01436","pmid":"37387789","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07299","title":"Therapeutic applications of thymosin peptides: a patent landscape 2018-present.","authors":"Quagliata, Michael; Papini, Anna Maria; Rovero, Paolo","year":2023,"journal":"Expert opinion on therapeutic patents, 33(12), 865-873","doi":"10.1080/13543776.2023.2298833","pmid":"38131310","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07300","title":"Semaglutide and Tirzepatide reduce alcohol consumption in individuals with obesity.","authors":"Quddos, Fatima; Hubshman, Zachary; Tegge, Allison; Sane, Daniel; Marti, Erin; Kablinger, Anita S; Gatchalian, Kirstin M; Kelly, Amber L; DiFeliceantonio, Alexandra G; Bickel, Warren K","year":2023,"journal":"Scientific reports, 13(1), 20998","doi":"10.1038/s41598-023-48267-2","pmid":"38017205","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07301","title":"Liver-Directed Therapy for Neuroendocrine Tumor Metastases in the Era of Peptide Receptor Radionuclide Therapy.","authors":"Rabei, Rana; Fidelman, Nicholas","year":2023,"journal":"Current treatment options in oncology, 24(12), 1994-2004","doi":"10.1007/s11864-023-01152-6","pmid":"38100020","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07302","title":"Change of CGRP Plasma Concentrations in Migraine after Discontinuation of CGRP-(Receptor) Monoclonal Antibodies.","authors":"Raffaelli, Bianca; Terhart, Maria; Fitzek, Mira Pauline; Lange, Kristin Sophie; Mecklenburg, Jasper; Overeem, Lucas Hendrik; Siebert, Anke; Storch, Elisabeth; Reuter, Uwe","year":2023,"journal":"Pharmaceutics, 15(1)","doi":"10.3390/pharmaceutics15010293","pmid":"36678920","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07303","title":"Open-label trials for CGRP-targeted drugs in migraine prevention: A narrative review.","authors":"Raffaelli, Bianca; De Icco, Roberto; Corrado, Michele; Terhart, Maria; Ailani, Jessica","year":2023,"journal":"Cephalalgia : an international journal of headache, 43(2), 3331024221137091","doi":"10.1177/03331024221137091","pmid":"36718044","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 13 open-label trials (ranging 12-264 weeks) of all five CGRP-targeting drugs for migraine prevention, no new safety concerns emerged beyond those seen in double-blind phases. More than 75% of patients remained on treatment after one year, with sustained reductions in migraine frequency and lasting quality of life improvements. Discontinuation rates were generally low, and the adverse event profile was consistent with the controlled trial data.","whyItMatters":"While randomized controlled trials prove a drug works, open-label extensions show whether it keeps working and stays safe over years of real-world-like use. This review confirms that CGRP-targeting peptide drugs maintain their benefits long-term with higher treatment adherence than older migraine preventives — critical information for patients and clinicians committing to ongoing therapy.","specificNumbers":"13 open-label trials · 5 drugs reviewed · duration 12-264 weeks · >75% retention at 1 year · 4 erenumab, 4 galcanezumab, 3 fremanezumab, 1 eptinezumab, 1 atogepant","methodology":"Narrative review of PubMed-indexed open-label trials of CGRP monoclonal antibodies (erenumab, galcanezumab, fremanezumab, eptinezumab) and the CGRP receptor antagonist atogepant. Safety, efficacy, and treatment adherence data were summarized and critically analyzed across 13 studies.","limitations":"Open-label trials lack placebo control, so efficacy estimates may be inflated by placebo effects and expectation bias. Patients who tolerated the drug in the double-blind phase are preferentially enrolled, creating selection bias. Not a systematic review with formal meta-analysis. Real-world adherence may differ from trial settings."},{"rthcId":"RPEP-07304","title":"The Impact of Glucagon-Like Peptide-1 Receptor Agonist on the Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus: A Meta-Analysis and Systematic Review.","authors":"Rahman, Ali; Alqaisi, Sura; Saith, Sunil E; Alzakhari, Rana; Levy, Ralph","year":2023,"journal":"Cardiology research, 14(4), 250-260","doi":"10.14740/cr1523","pmid":"37559715","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07305","title":"Cell-permeable chameleonic peptides: Exploiting conformational dynamics in de novo cyclic peptide design.","authors":"Ramelot, Theresa A; Palmer, Jonathan; Montelione, Gaetano T; Bhardwaj, Gaurav","year":2023,"journal":"Current opinion in structural biology, 80, 102603","doi":"10.1016/j.sbi.2023.102603","pmid":"37178478","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07306","title":"Deep mutational scanning and machine learning uncover antimicrobial peptide features driving membrane selectivity.","authors":"Randall, Justin R; Vieira, Luiz C; Wilke, Claus O; Davies, Bryan W","year":2023,"journal":"Research square","doi":"10.21203/rs.3.rs-3280212/v1","pmid":"37790501","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07307","title":"Fabrication, characterization and evaluation of a new designed botulinum toxin-cell penetrating peptide nanoparticulate complex.","authors":"Ravari, Nazanin Shabani; Sheikhlou, Maryam Ghareh; Goodarzi, Navid; Kharazian, Bahar; Amini, Mohsen; Atyabi, Fatemeh; Nasrollahi, Saman A; Dinarvand, Rassoul","year":2023,"journal":"Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences, 31(1), 1-12","doi":"10.1007/s40199-023-00462-2","pmid":"37209247","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07308","title":"Retatrutide: a triple incretin receptor agonist for obesity management.","authors":"Ray, Avik","year":2023,"journal":"Expert opinion on investigational drugs, 32(11), 1003-1008","doi":"10.1080/13543784.2023.2276754","pmid":"37902090","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07309","title":"The influence of a synthetic growth hormone-releasing hormone analogue G11 and opioid peptide biphalin on selected fibroblasts parameters relevant to wound healing.","authors":"Redkiewicz, Patrycja; Dyniewicz, Jolanta; Witkowska, Ewa; Misicka, Aleksandra; Lipiński, Piotr F J","year":2023,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 29(9), e3487","doi":"10.1002/psc.3487","pmid":"36898693","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07310","title":"Mitochondrial metabolites predict adverse cardiovascular events in individuals with diabetes.","authors":"Regan, Jessica A; Mentz, Robert J; Nguyen, Maggie; Green, Jennifer B; Truby, Lauren K; Ilkayeva, Olga; Newgard, Christopher B; Buse, John B; Sourij, Harald; Sjöström, C David; Sattar, Naveed; McGarrah, Robert W; Zheng, Yinggan; McGuire, Darren K; Standl, Eberhard; Armstrong, Paul; Peterson, Eric D; Hernandez, Adrian F; Holman, Rury R; Shah, Svati H","year":2023,"journal":"JCI insight, 8(17)","doi":"10.1172/jci.insight.168563","pmid":"37552540","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07311","title":"Orally-delivered insulin-peptide nanocomplexes enhance transcytosis from cellular depots and improve diabetic blood glucose control.","authors":"Rehmani, Sahrish; McLaughlin, Christopher M; Eltaher, Hoda M; Moffett, R Charlotte; Flatt, Peter R; Dixon, James E","year":2023,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 360, 93-109","doi":"10.1016/j.jconrel.2023.06.006","pmid":"37315695","tags":["insulin","cell-penetrating-peptide"],"studyType":"preclinical-drug-delivery","evidenceStrength":"moderate-preclinical","keyFinding":"Insulin-GET nanocomplexes (140 nm, +27.10 mV charge) enhanced insulin transport across differentiated Caco-2 intestinal epithelium by more than 22-fold compared to free insulin. The nanocomplexes accumulated inside cells and were progressively released from both the apical and basal surfaces, effectively turning gut cells into sustained-release depots.\n\nThe complexes showed enhanced proteolytic stability (resisting enzymatic destruction) and retained significant biological activity. In streptozotocin-induced diabetic mice, serial oral dosing of Insulin-GET nanocomplexes controlled elevated blood glucose levels over several days without compromising intestinal barrier integrity or cell viability.","whyItMatters":"Millions of people with diabetes inject insulin multiple times daily. An oral insulin pill would dramatically improve quality of life and treatment adherence, but the gut's harsh environment and poor absorption have prevented it. This cell-penetrating peptide approach solves multiple problems at once — protecting insulin from digestion, shuttling it across the intestinal wall, and creating intracellular depots for sustained release. The simplicity of the complexation platform also makes it potentially applicable to other peptide drugs.","specificNumbers":"140 nm NCs; +27.10 mV; >22-fold translocation increase; blood glucose control over several days in STZ mice","methodology":"Insulin was complexed with GET cell-penetrating peptide via electrostatic interaction to form nanocomplexes. In vitro: transport tested in differentiated Caco-2 intestinal epithelium monolayers; biological activity confirmed via insulin-responsive reporter assays; proteolytic stability assessed. In vivo: oral delivery tested in streptozotocin-induced diabetic mice with serial dosing and blood glucose monitoring.","limitations":"Mouse model only; Caco-2 model doesn't fully replicate human intestine; oral bioavailability not quantified; long-term safety unknown; STZ model represents type 1 diabetes only."},{"rthcId":"RPEP-07312","title":"Harnessing αβ T cell receptor mechanobiology to achieve the promise of immuno-oncology.","authors":"Reinherz, Ellis L; Hwang, Wonmuk; Lang, Matthew J","year":2023,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 120(27), e2215694120","doi":"10.1073/pnas.2215694120","pmid":"37339184","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07313","title":"Modulation of neurotrophic factors in the treatment of dementia, stroke and TBI: Effects of Cerebrolysin.","authors":"Rejdak, Konrad; Sienkiewicz-Jarosz, Halina; Bienkowski, Przemyslaw; Alvarez, Anton","year":2023,"journal":"Medicinal research reviews, 43(5), 1668-1700","doi":"10.1002/med.21960","pmid":"37052231","tags":[],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Neurotrophic factors (NTFs) — including NGF, IGF-1, BDNF, VEGF, and TNF-α — are deeply involved in the pathophysiology of dementia, stroke, and traumatic brain injury, and represent high-value therapeutic targets. The neuropeptide preparation Cerebrolysin has been shown to mimic the activities of these NTFs and modulate the expression levels of endogenous neurotrophic factors.\n\nCerebrolysin demonstrated beneficial effects in both in vitro studies and clinical trials across all three conditions, acting through neuroplasticity, neurogenesis, angiogenesis, and anti-inflammatory pathways. The review emphasizes that these NTFs don't work in isolation — their signaling networks interact, and Cerebrolysin appears to engage multiple pathways simultaneously.","whyItMatters":"Dementia, stroke, and TBI are among the leading causes of disability worldwide, and treatment options remain limited. This review maps the neurotrophic factor network underlying these conditions and positions Cerebrolysin as a multi-target neuropeptide therapy — an approach that may be more effective than targeting a single growth factor, given how interconnected these signaling pathways are.","specificNumbers":"5 NTFs reviewed (NGF, IGF-1, BDNF, VEGF, TNF-α) · 3 conditions covered (dementia, stroke, TBI) · 4 mechanisms: neuroplasticity, neurogenesis, angiogenesis, inflammation","methodology":"This is a comprehensive narrative review that synthesizes published preclinical and clinical evidence on five neurotrophic factors and their roles in dementia, stroke, and TBI. The review evaluates the biochemistry, signaling networks, and therapeutic potential of these NTFs, with a focus on how Cerebrolysin modulates their expression and activity.","limitations":"As a narrative review, the paper synthesizes existing evidence rather than generating new data. The clinical evidence for Cerebrolysin varies in quality across the three conditions, and some of the clinical trials reviewed may have limitations in design or sample size. The review focuses on selected NTFs rather than the complete neurotrophic landscape."},{"rthcId":"RPEP-07314","title":"Growth hormone-releasing hormone agonist attenuates vascular calcification in diabetic db/db mice.","authors":"Ren, Hao-Lin; Cai, Ruiping; Xue, Ruize; Zhang, Yaoxia; Xu, Qian; Zhang, Xianyang; Cai, RenZhi; Sha, Wei; Schally, Andrew V; Zhou, Ming-Sheng","year":2023,"journal":"Frontiers in cardiovascular medicine, 10, 1102525","doi":"10.3389/fcvm.2023.1102525","pmid":"36742073","tags":[],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"A growth hormone-releasing hormone agonist (MR409) reversed vascular calcification in diabetic mice over 8 weeks of daily treatment. The peptide eliminated calcium plaques from heart valves (confirmed by echocardiography), improved blood vessel function, and reduced vascular structural damage — all without significantly affecting growth hormone levels.\n\nThe mechanism involved upregulation of the anti-calcifying protein Klotho, reduction of vascular reactive oxygen species (ROS), and suppression of bone-forming genes (Runx2, ALP) that drive calcium deposition in blood vessels. The peptide also improved the lipid profile of diabetic mice.","whyItMatters":"Vascular calcification — calcium buildup in blood vessel walls and heart valves — is a major killer in diabetes and has no approved treatment. Current medicine can't reverse it once it starts. This study shows a peptide analog of GHRH can not only prevent but appear to reverse established calcification in diabetic mice, without triggering the problematic growth hormone elevation that limits other GHRH-based therapies. If this translates to humans, it could address a massive unmet medical need.","specificNumbers":"8-week daily treatment · calcium plaques eliminated from heart valves · ALP and Runx2 expression reduced · Klotho upregulated · ROS reduced · lipid profile improved · no significant GH axis effect","methodology":"Animal study using db/db diabetic mice (a standard genetic model of type 2 diabetes). Mice received daily subcutaneous injections of MR409 (a GHRH agonist) for 8 weeks. Researchers assessed vascular calcification using echocardiography and calcium staining, measured osteogenic markers (ALP, Runx2), anti-calcifying protein Klotho, reactive oxygen species, lipid profiles, and endothelium-dependent vascular relaxation.","limitations":"Mouse model only — db/db mice develop severe diabetes that may not fully represent the gradual vascular calcification seen in human diabetics over decades. The 8-week treatment period is short relative to the chronic nature of human vascular disease. No dose-response data mentioned. The apparent disappearance of heart valve calcium plaques on echo needs histological confirmation. Long-term safety and effects on other organs were not assessed."},{"rthcId":"RPEP-07315","title":"Heating affects protein digestion of skimmed goat milk under simulated infant conditions.","authors":"Ren, Qing; Boiani, Mattia; He, Tao; Wichers, Harry J; Hettinga, Kasper A","year":2023,"journal":"Food chemistry, 402, 134261","doi":"10.1016/j.foodchem.2022.134261","pmid":"36137390","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Heating goat milk at temperatures ≥80°C caused more extensive gastric clot formation with higher protein digestion rates, but also resulted in more undigested whey proteins due to severe aggregation.\n\nβ-Casein was the major source of bioactive peptides during digestion. Milk heated at 65°C produced the highest abundance of bioactive peptides, while temperatures above 75°C reduced bioactive peptide levels because the peptides were further cleaved into smaller, less bioactive fragments. The study demonstrated that different heating temperatures induce different degrees of whey protein denaturation, which directly affects digestion outcomes.","whyItMatters":"Goat milk-based infant formulas are a growing market, and processing conditions directly affect nutritional quality. This study shows that the temperature used during manufacturing can significantly impact how well infants digest the milk proteins and how many beneficial peptides are released. The findings could help optimize formula processing to maximize nutritional benefits.","specificNumbers":"","methodology":"Skimmed goat milk was heated at various temperatures (up to and above 80°C) and then subjected to simulated infant gastrointestinal digestion. Unlike most previous studies that only analyzed the liquid portion, this study examined both the supernatant and gastric clot. Researchers used peptidomic analysis to identify and quantify bioactive peptides released during digestion at each temperature.","limitations":"The study used simulated infant digestion in the laboratory, not actual infant digestion, which may differ in important ways. Only skimmed goat milk was tested, so results may not apply to whole milk or formula products with added ingredients. The bioactive potential of the identified peptides was inferred from database matching rather than tested experimentally for biological activity. The study did not assess whether the differences would have meaningful nutritional impacts in real infants."},{"rthcId":"RPEP-07316","title":"Pharmacokinetics, biodistribution and toxicology of novel cell-penetrating peptides.","authors":"Reveret, L; Leclerc, M; Morin, F; Émond, V; Calon, F","year":2023,"journal":"Scientific reports, 13(1), 11081","doi":"10.1038/s41598-023-37280-0","pmid":"37422520","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07317","title":"The blood pressure lowering effects of glucagon-like peptide-1 receptor agonists: A mini-review of the potential mechanisms.","authors":"Ribeiro-Silva, Joao Carlos; Tavares, Caio A M; Girardi, Adriana C C","year":2023,"journal":"Current opinion in pharmacology, 69, 102355","doi":"10.1016/j.coph.2023.102355","pmid":"36857807","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07318","title":"Novel evidence of Thymosin α1 immunomodulatory properties in SARS-CoV-2 infection: Effect on innate inflammatory response in a peripheral blood mononuclear cell-based in vitro model.","authors":"Ricci, Daniela; Etna, Marilena Paola; Severa, Martina; Fiore, Stefano; Rizzo, Fabiana; Iannetta, Marco; Andreoni, Massimo; Balducci, Stefano; Stefanelli, Paola; Palamara, Anna Teresa; Coccia, Eliana Marina","year":2023,"journal":"International immunopharmacology, 117, 109996","doi":"10.1016/j.intimp.2023.109996","pmid":"36933449","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07319","title":"Successful treatment of binge eating disorder with the GLP-1 agonist semaglutide: A retrospective cohort study.","authors":"Richards, Jesse; Bang, Neha; Ratliff, Erin L; Paszkowiak, Maria A; Khorgami, Zhamak; Khalsa, Sahib S; Simmons, W Kyle","year":2023,"journal":"Obesity pillars, 7, 100080","doi":"10.1016/j.obpill.2023.100080","pmid":"37990682","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07320","title":"Significant Decrease in Alcohol Use Disorder Symptoms Secondary to Semaglutide Therapy for Weight Loss: A Case Series.","authors":"Richards, Jesse R; Dorand, Madisen Fae; Royal, Kyleigh; Mnajjed, Lana; Paszkowiak, Maria; Simmons, W Kyle","year":2023,"journal":"The Journal of clinical psychiatry, 85(1)","doi":"10.4088/JCP.23m15068","pmid":"38019594","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"All 6 patients (100%) with positive Alcohol Use Disorder Identification Test (AUDIT) screenings showed significant reduction in AUD symptoms after starting semaglutide therapy for weight loss. The mean AUDIT score decreased by 9.5 points, a statistically significant improvement (P value reported as significant via paired t-test).\n\nThis clinical observation is consistent with preclinical animal data showing that GLP-1 receptor agonists can reduce alcohol consumption. Currently, only 3 FDA-approved medications exist for AUD treatment, making the potential of semaglutide as an additional option clinically meaningful.","whyItMatters":"Alcohol use disorder is a leading cause of preventable death worldwide, yet only three FDA-approved drugs exist to treat it. If semaglutide and other GLP-1 receptor agonists can genuinely reduce alcohol cravings and consumption — as both animal studies and now this human case series suggest — it could open an entirely new treatment avenue for a condition that remains stubbornly difficult to manage.","specificNumbers":"","methodology":"The researchers conducted a retrospective chart review to identify patients prescribed semaglutide for weight loss who also had positive AUD screenings (AUDIT score > 8) before starting semaglutide. Six patients meeting these criteria were identified. Their AUDIT scores before and after semaglutide therapy were compared using a paired t-test.","limitations":"This is a case series of only 6 patients with no control group, no randomization, and no blinding. The retrospective design means the findings could be influenced by confounding factors — for example, patients may have changed drinking behavior due to nausea from semaglutide, weight loss motivation, or other lifestyle changes. The AUDIT score improvement could partially reflect reduced caloric intake from alcohol rather than reduced craving specifically. Much larger randomized controlled trials are needed."},{"rthcId":"RPEP-07321","title":"The effects of subcutaneous Tirzepatide on obesity and overweight: a systematic review and meta-regression analysis of randomized controlled trials.","authors":"Rohani, Pejman; Malekpour Alamdari, Nasser; Bagheri, Seyedeh Elaheh; Hekmatdoost, Azita; Sohouli, Mohammad Hassan","year":2023,"journal":"Frontiers in endocrinology, 14, 1230206","doi":"10.3389/fendo.2023.1230206","pmid":"37621649","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07322","title":"Peptide cargo administration: current state and applications.","authors":"Rohira, Harsha; Arora, Aditi; Kaur, Prasanjeet; Chugh, Archana","year":2023,"journal":"Applied microbiology and biotechnology, 107(10), 3153-3181","doi":"10.1007/s00253-023-12512-5","pmid":"37052636","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07323","title":"Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial conducted in the USA.","authors":"Rosenstock, Julio; Frias, Juan; Jastreboff, Ania M; Du, Yu; Lou, Jitong; Gurbuz, Sirel; Thomas, Melissa K; Hartman, Mark L; Haupt, Axel; Milicevic, Zvonko; Coskun, Tamer","year":2023,"journal":"Lancet (London, England), 402(10401), 529-544","doi":"10.1016/S0140-6736(23)01053-X","pmid":"37385280","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"At 24 weeks, retatrutide produced dose-dependent HbA1c reductions:\n\n• 0.5 mg: −0.43%\n• 4 mg (escalation): −1.39%\n• 4 mg (no escalation): −1.30%\n• 8 mg (slow escalation): −1.99%\n• 8 mg (fast escalation): −1.88%\n• 12 mg (escalation): −2.02%\n• Placebo: −0.01%\n• Dulaglutide 1.5 mg: −1.41%\n\nAt 36 weeks, body weight decreased dose-dependently:\n\n• 0.5 mg: −3.19%\n• 4 mg (escalation): −7.92%\n• 4 mg (no escalation): −10.37%\n• 8 mg (slow): −16.81%\n• 8 mg (fast): −16.34%\n• 12 mg: −16.94%\n• Placebo: −3.00%\n• Dulaglutide: −2.02%\n\nThe 8 mg and 12 mg doses significantly outperformed both placebo (p<0.0001) and dulaglutide (p<0.0001 for weight; p≤0.0019 for HbA1c).","whyItMatters":"This is a landmark trial for the multi-agonist approach to metabolic disease. While tirzepatide (dual GIP/GLP-1 agonist) has already transformed obesity and diabetes treatment, retatrutide adds a third receptor — glucagon — which drives additional energy expenditure and fat burning. The nearly 17% weight loss achieved in type 2 diabetes patients at 36 weeks rivals results seen in dedicated obesity trials, suggesting the triple-agonist approach could become the next major advance in metabolic medicine.","specificNumbers":"","methodology":"This was a randomized, double-blind, double-dummy, placebo-controlled and active comparator-controlled, parallel-group, phase 2 trial conducted at 42 US research centers. 281 adults (age 18-75) with type 2 diabetes (HbA1c 7.0-10.5%, BMI 25-50 kg/m²) were randomized to eight groups receiving weekly injections of placebo, dulaglutide 1.5 mg, or retatrutide at six dose/escalation regimens. Treatment lasted 36 weeks with stratification by baseline HbA1c and BMI. Primary endpoint was HbA1c change at 24 weeks.","limitations":"This was a phase 2 trial with 281 participants — large enough to establish dose-response but not powered for rare safety events. The trial was conducted only in the US with 84% White participants, limiting generalizability. The 36-week duration doesn't capture long-term safety or weight loss plateau effects. The active comparator was dulaglutide (an older GLP-1 agonist), not semaglutide or tirzepatide, making direct comparisons to newer drugs impossible from this trial alone."},{"rthcId":"RPEP-07324","title":"Involvement of Substance P (SP) and Its Related NK1 Receptor in Primary Sjögren's Syndrome (pSS) Pathogenesis.","authors":"Rosso, Pamela; Fico, Elena; Colafrancesco, Serena; Bellizzi, Mario Giuseppe; Priori, Roberta; Cerbelli, Bruna; Leopizzi, Martina; Giordano, Carla; Greco, Antonio; Tirassa, Paola; Severini, Cinzia; Fusconi, Massimo","year":2023,"journal":"Cells, 12(10)","doi":"10.3390/cells12101347","pmid":"37408182","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07325","title":"Medullary tachykinin precursor 1 neurons promote rhythmic breathing.","authors":"Rousseau, Jean-Philippe; Furdui, Andreea; Silveira Scarpellini, Carolina da; Horner, Richard L; Montandon, Gaspard","year":2023,"journal":"eLife, 12","doi":"10.7554/eLife.85575","pmid":"37458576","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tachykinin precursor 1 (Tac1) neurons in the preBötzinger Complex (preBötC) — the brain's breathing rhythm generator — promote rhythmic breathing when stimulated. Using optogenetics, researchers showed that activating these substance P-expressing neurons stimulated breathing in both anesthetized and freely moving mice, triggered locomotion, and critically, overcame opioid-induced respiratory depression. These findings establish Tac1 neurons as a key excitatory population with dual roles in breathing and motor behavior.","whyItMatters":"Opioid-induced respiratory depression is the primary cause of death in opioid overdose. The discovery that stimulating substance P-expressing neurons in the breathing center can overcome opioid-induced breathing suppression identifies a potential new approach to preventing overdose deaths. This connects the well-known neuropeptide substance P to a critical unmet medical need.","specificNumbers":"Tac1-cre mouse model · ChETA channelrhodopsin-2 optogenetics · preBötC stimulation · promoted breathing in anesthetized + freely moving mice · overcame opioid respiratory depression · triggered locomotion","methodology":"Researchers used Tac1-cre transgenic mice with adeno-associated virus delivering excitatory channelrhodopsin-2 (ChETA) targeted to the preBötzinger Complex. They combined histological characterization, optogenetic stimulation, respiratory measurements, and behavioral assays to assess the effects of activating Tac1 neurons on breathing patterns, motor behavior, and opioid-induced respiratory depression in both anesthetized and freely moving animals.","limitations":"This is a mouse study using optogenetic tools that are not directly translatable to human clinical use. The preBötC is a small, deep brainstem structure that would be difficult to target therapeutically in humans. The study focused on acute stimulation effects; long-term or repeated stimulation effects were not assessed. The relative contributions of substance P signaling versus glutamatergic signaling from these dual-phenotype neurons were not fully separated."},{"rthcId":"RPEP-07326","title":"Real-world clinical effectiveness of once-weekly semaglutide in patients with type 2 diabetes: a systematic literature review.","authors":"Ruan, Zhen; Jiang, Yixuan; Shi, Honghao; Jia, Ruxu; Ung, Carolina Oi Lam; Hu, Hao","year":2023,"journal":"Expert review of clinical pharmacology, 16(2), 161-176","doi":"10.1080/17512433.2023.2174099","pmid":"36706368","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07327","title":"The effect of Dulaglutide on glycemic and weight control in patients with type 2 diabetes.","authors":"Ruda, Alexandru Ioan; Ciobanu, Dana Mihaela; Inceu, Georgeta; Rusu, Adriana; Roman, Gabriela","year":2023,"journal":"Medicine and pharmacy reports, 96(1), 52-57","doi":"10.15386/mpr-2425","pmid":"36818328","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"HbA1c decreased significantly at both time points: -1.3% at 6 months (p<0.001) and -2.0% at 12 months (p<0.001). Body weight decreased by -2.0 kg at 6 months (p=0.002) and -3.5 kg at 12 months (p=0.001). A reduction in insulin dose was also observed in patients taking concurrent insulin.\n\nThe improvements were progressive — results at 12 months were better than at 6 months for both HbA1c and weight, suggesting continued benefit with ongoing treatment.","whyItMatters":"Clinical trials test drugs under ideal conditions with carefully selected patients, but real-world effectiveness can differ. This study confirms that dulaglutide delivers meaningful blood sugar and weight improvements in everyday clinical practice — in patients who have already failed other treatments. The progressive improvement from 6 to 12 months is reassuring for long-term use, and the insulin-sparing effect suggests dulaglutide may simplify complex diabetes regimens.","specificNumbers":"","methodology":"This retrospective study reviewed medical records of 50 type 2 diabetes patients from a single center who were inadequately controlled on previous antidiabetic medications and started on dulaglutide 1.5mg weekly. Data were collected at baseline, 6 months (50 patients), and 12 months (40 patients — 10 were lost to follow-up or discontinued). Primary outcomes were changes in HbA1c and body weight.","limitations":"This is a small, single-center retrospective study without a control group, making it impossible to separate dulaglutide's effects from natural disease progression or concurrent treatment changes. Ten patients (20%) were lost between the 6- and 12-month assessments, which could introduce bias if those who dropped out had worse outcomes. The sample of 50 patients is too small for meaningful subgroup analyses. No adverse event data is reported in the abstract."},{"rthcId":"RPEP-07328","title":"Alopecia as an emerging adverse event to CGRP monoclonal antibodies: Cases Series, evaluation of FAERS, and literature review.","authors":"Ruiz, Miguel; Cocores, Alexandra; Tosti, Antonella; Goadsby, Peter J; Monteith, Teshamae S","year":2023,"journal":"Cephalalgia : an international journal of headache, 43(2), 3331024221143538","doi":"10.1177/03331024221143538","pmid":"36739513","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07329","title":"Amino acids contribute to adaptive thermogenesis. New insights into the mechanisms of action of recent drugs for metabolic disorders are emerging.","authors":"Ruocco, Chiara; Malavazos, Alexis Elias; Ragni, Maurizio; Carruba, Michele O; Valerio, Alessandra; Iacobellis, Gianluca; Nisoli, Enzo","year":2023,"journal":"Pharmacological research, 195, 106892","doi":"10.1016/j.phrs.2023.106892","pmid":"37619907","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07330","title":"Cellular uptake and trafficking of peptide-based drug delivery systems for miRNA.","authors":"Ruseska, Ivana; Zimmer, Andreas","year":2023,"journal":"European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 191, 189-204","doi":"10.1016/j.ejpb.2023.08.019","pmid":"37666365","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07331","title":"Anti-calcitonin gene-related peptide monoclonal antibodies for the treatment of vestibular migraine: A prospective observational cohort study.","authors":"Russo, Cinzia Valeria; Saccà, Francesco; Braca, Simone; Sansone, Mattia; Miele, Angelo; Stornaiuolo, Antonio; De Simone, Roberto","year":2023,"journal":"Cephalalgia : an international journal of headache, 43(4), 3331024231161809","doi":"10.1177/03331024231161809","pmid":"36946234","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Fifty vestibular migraine patients treated with anti-CGRP monoclonal antibodies (erenumab, fremanezumab, or galcanezumab) over 18 months:\n\n- **Vertigo**: 45/50 patients (90%) achieved ≥50% reduction in vertigo frequency\n- **Headache**: 43/50 patients (86%) achieved ≥50% reduction in headache frequency\n- **Disability**: 40/50 patients (80%) had ≥50% reduction in MIDAS disability score\n- **All three metrics**: 39/50 patients (78%) improved on vertigo, headache, AND disability simultaneously\n- **Dizziness days**: Dropped from 10.3 ± 1.9 days/month at baseline to 0.8 ± 0.3 days/month at 12 months (difference 9.5 days, 95% CI 3.6-15.4, p<0.001)","whyItMatters":"Vestibular migraine affects millions but has no specifically approved treatment — patients often cycle through repurposed drugs with limited success. A 90% response rate for vertigo reduction is remarkable and could establish anti-CGRP antibodies as a game-changing treatment for this debilitating condition. The finding that CGRP is present in inner ear structures also provides a biological rationale for why these drugs work on vestibular symptoms.","specificNumbers":"","methodology":"This was a prospective observational cohort study of 50 vestibular migraine patients treated with one of three anti-CGRP monoclonal antibodies. Outcomes measured over 18 months included mean monthly headache days, dizziness/vestibular symptom days, pain intensity, and migraine-related disability (MIDAS score). Response was defined as ≥50% reduction in each parameter.","limitations":"This was an observational study without a control group or placebo comparison, so the placebo effect cannot be ruled out. The sample size of 50 patients is modest. Three different anti-CGRP antibodies were used, making it difficult to compare individual drug efficacy. The patient population was from a single center. Randomized controlled trials are needed to confirm these promising results."},{"rthcId":"RPEP-07332","title":"Assessment of Safety and Prophylactic Efficacy of the EpiVacCorona Peptide Vaccine for COVID-19 Prevention (Phase III).","authors":"Ryzhikov, Alexander B; Ryzhikov, Evgeny A; Bogryantseva, Marina P; Usova, Svetlana V; Nechaeva, Elena A; Danilenko, Elena D; Pyankov, Stepan A; Gudymo, Andrey S; Moiseeva, Anastasiya A; Onkhonova, Galina S; Pyankov, Oleg V; Sleptsova, Ekaterina S; Lomakin, Nikita V; Vasilyeva, Veronika S; Tulikov, Mikhail V; Gusarov, Vitaly G; Pulin, Andrey A; Balalaeva, Maria A; Erofeeva, Svetlana B; Terpigorev, Stanislav A; Rychkova, Olga A; Petrov, Ivan M; Delian, Viktoriia Y; Rafalskiy, Vladimir V; Tyranovets, Sergey V; Gavrilova, Elena V; Maksyutov, Rinat A","year":2023,"journal":"Vaccines, 11(5)","doi":"10.3390/vaccines11050998","pmid":"37243102","tags":["peptide-vaccines","infectious-disease","immunology"],"studyType":"human-rct","evidenceStrength":"moderate","keyFinding":"In a double-blind, placebo-controlled Phase III trial of 3,000 volunteers aged 18 and older, the two-dose EpiVacCorona vaccine administered intramuscularly demonstrated a prophylactic efficacy of 82.5% (95% CI: 75.3–87.6%) against COVID-19.\n\nThe safety profile was favorable: mild local reactions occurred in no more than 27% of vaccinated individuals, and mild systemic reactions in no more than 14%. The researchers concluded the vaccine was safe enough and effective enough for regular seasonal COVID-19 prevention.","whyItMatters":"Most COVID-19 vaccines use mRNA, viral vectors, or inactivated virus technology. EpiVacCorona represents a fundamentally different approach — using chemically synthesized peptide fragments of the virus. If peptide vaccines can truly achieve high efficacy, they offer potential advantages: simpler manufacturing, easier storage, and a more targeted immune response with fewer off-target effects. This trial is significant as proof-of-concept for the peptide vaccine platform in a real pandemic setting.","specificNumbers":"n=3000; 82.5% efficacy (95% CI 75.3-87.6%); local reactions ≤27%; systemic reactions ≤14%; two-dose intramuscular series","methodology":"This was a multicenter, double-blind, placebo-controlled, randomized Phase III clinical trial. Three thousand volunteers aged 18 and older were randomized to receive either two doses of the EpiVacCorona peptide vaccine or placebo, administered intramuscularly. The study evaluated both safety (adverse reactions) and prophylactic efficacy (prevention of COVID-19 infection).","limitations":"This vaccine was developed by a Russian government laboratory, and the efficacy claims were disputed by some independent Russian and international scientists who questioned the trial methodology and endpoint definitions. The study was conducted during a specific period of the pandemic, and it's unclear how the vaccine would perform against later variants. Independent replication of the results has not been reported. The abstract does not detail the specific peptide antigens used or the immunological correlates of protection."},{"rthcId":"RPEP-07333","title":"Conformations of Macrocyclic Peptides Sampled by Nuclear Magnetic Resonance: Models for Cell-Permeability.","authors":"Rüdisser, Simon H; Matabaro, Emmanuel; Sonderegger, Lukas; Güntert, Peter; Künzler, Markus; Gossert, Alvar D","year":2023,"journal":"Journal of the American Chemical Society, 145(50), 27601-27615","doi":"10.1021/jacs.3c09367","pmid":"38062770","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07334","title":"Cancer Wars: Revenge of the AMPs (Antimicrobial Peptides), a New Strategy against Colorectal Cancer.","authors":"Răileanu, Mina; Bacalum, Mihaela","year":2023,"journal":"Toxins, 15(7)","doi":"10.3390/toxins15070459","pmid":"37505728","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Three antimicrobial peptides — Melittin, Cecropin A, and a Cecropin A-Melittin hybrid — were tested against 3D colorectal cancer spheroids. All three peptides reduced cell viability and compromised spheroid structure. Melittin and the hybrid peptide were the most effective, showing greater anticancer activity than Cecropin A alone. The peptides increased ATP and LDH release (indicators of membrane damage and cell death), arrested cancer cells in the G2/M phase of the cell cycle, and increased the number of senescent (non-dividing) cells.","whyItMatters":"Colorectal cancer is the third most common cancer worldwide and often develops resistance to conventional chemotherapy. Antimicrobial peptides like Melittin and Cecropin A can selectively target cancer cells through membrane disruption mechanisms that are harder for tumors to develop resistance against, offering a potential alternative or complement to standard treatments.","specificNumbers":"3 peptides tested · 2 colorectal cancer spheroid models · cell viability reduced · ATP and LDH elevated · G2/M cell cycle arrest · increased cellular senescence · Melittin and hybrid most effective","methodology":"In vitro study using two human colorectal cancer cell line-derived 3D spheroids (a more realistic model than flat cell cultures). Cell viability was measured using MTT, LDH, and ATP assays at different peptide concentrations. Cell cycle analysis and cellular senescence assays were performed to understand mechanisms of action.","limitations":"In vitro study using 3D spheroids but no in vivo animal testing. Melittin is known to have toxicity to normal cells (it is bee venom peptide), and the study does not provide detailed selectivity data comparing cancer vs normal cell effects. Specific concentrations and dose-response curves are not detailed in the abstract."},{"rthcId":"RPEP-07335","title":"Potential benefits of intranasal neuropeptide Y include sustained extinction of fear memory.","authors":"Sabban, Esther L; Serova, Lidia; Nahvi, Roxanna J; Liu, Xiaoping","year":2023,"journal":"Journal of neuroendocrinology, 35(11), e13279","doi":"10.1111/jne.13279","pmid":"37157881","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07336","title":"A head-to-head observational cohort study on the efficacy and safety of monoclonal antibodies against calcitonin gene-related peptide for chronic and episodic migraine.","authors":"Saccà, Francesco; Braca, Simone; Sansone, Mattia; Miele, Angelo; Stornaiuolo, Antonio; De Simone, Roberto; Russo, Cinzia Valeria","year":2023,"journal":"Headache, 63(6), 788-794","doi":"10.1111/head.14528","pmid":"37254581","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07337","title":"The Role of Substance P Within Traumatic Brain Injury and Implications for Therapy.","authors":"Safwat, Adam; Helmy, Adel; Gupta, Arun","year":2023,"journal":"Journal of neurotrauma, 40(15-16), 1567-1583","doi":"10.1089/neu.2022.0510","pmid":"37132595","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07338","title":"Combining Chemical Protein Synthesis and Random Nonstandard Peptides Integrated Discovery for Modulating Biological Processes.","authors":"Saha, Abhishek; Suga, Hiroaki; Brik, Ashraf","year":2023,"journal":"Accounts of chemical research, 56(14), 1953-1965","doi":"10.1021/acs.accounts.3c00178","pmid":"37312234","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07339","title":"Cardiac-Targeting Peptide: From Discovery to Applications.","authors":"Sahagun, Daniella; Zahid, Maliha","year":2023,"journal":"Biomolecules, 13(12)","doi":"10.3390/biom13121690","pmid":"38136562","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07340","title":"Efficacy and safety of polyethylene glycol loxenatide in type 2 diabetic patients: a systematic review and meta-analysis of randomized controlled trials.","authors":"Salamah, Hazem Mohamed; Marey, Ahmed; Elsayed, Esraa; Hasan, Mohammed Tarek; Mahmoud, Abdelrahman; Abualkhair, Khaled Alsayed; Abo-Elnour, Dina Essam; Abdelhaleem, Ibrahim Abdelmonaem; Abd-Elgawad, Mohamed","year":2023,"journal":"Scientific reports, 13(1), 19041","doi":"10.1038/s41598-023-46274-x","pmid":"37923756","tags":["glp-1-agonists"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"PEG-loxenatide (PEX168), a long-acting pegylated GLP-1 receptor agonist derived from exenatide, significantly improved blood sugar control when added to metformin. The meta-analysis of 6 RCTs with 1,248 patients found that PEX168 plus metformin significantly reduced fasting blood glucose (MD = -1.20 mmol/L) and HbA1c compared to metformin alone.\n\nWeight loss was striking in obese patients — a 5.46 kg reduction versus controls — but no weight change occurred in non-obese patients. PEX168 monotherapy at 100, 200, and 300 μg showed comparable diabetes control to metformin. The 100 μg dose combined with metformin offered the best balance of efficacy and safety, while the 200 μg combination had more nausea and vomiting.","whyItMatters":"PEG-loxenatide is a Chinese-developed GLP-1 agonist that offers once-weekly dosing through pegylation of exenatide. This meta-analysis provides the most comprehensive evidence synthesis to date, showing it's a viable option for patients who don't achieve adequate control with metformin alone. The selective weight loss in obese but not non-obese patients is an interesting pharmacological distinction from other GLP-1 drugs.","specificNumbers":"6 RCTs · n=1,248 · FBG: MD = -1.20 mmol/L (p<0.001) · Weight loss in obese: -5.46 kg (p<0.0001) · Weight in non-obese: no change (p=0.83) · Doses: 100, 200, 300 μg · GI side effects more common (p<0.05)","methodology":"Systematic review and meta-analysis of randomized controlled trials. The authors searched PubMed, Scopus, Cochrane Library, and Web of Science through April 2023. Six RCTs with 1,248 participants were included. Outcomes were analyzed using mean differences for continuous data and risk ratios for binary outcomes with 95% confidence intervals. Subgroup analyses examined different doses and obese versus non-obese patients.","limitations":"Only 6 trials were available, limiting statistical power for subgroup analyses. All trials were likely conducted in Chinese populations, which may limit generalizability to other ethnic groups. The trials varied in design (monotherapy vs. combination). Long-term safety and cardiovascular outcomes data were not available. The authors note findings should be interpreted with caution due to the small number of trials."},{"rthcId":"RPEP-07341","title":"Designing Potent Anticancer Peptides by Aurein 1.2 Key Residues Mutation and Catenate Cell-Penetrating Peptide.","authors":"Salarpour Garnaie, Hamta; Shahabi, Arman; Geranmayeh, Mohammad Hossein; Barzegar, Abolfazel; Yari Khosroushahi, Ahmad","year":2023,"journal":"Advanced pharmaceutical bulletin, 13(3), 583-591","doi":"10.34172/apb.2023.063","pmid":"37646048","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07342","title":"Increased delivery and cytotoxicity of doxorubicin in HeLa cells using the synthetic cationic peptide pEM-2 functionalized liposomes.","authors":"Salas Sanzana, Diego; Flores Faúndez, Emilia; Meléndez, Jaime; Soto-Arriaza, Marco","year":2023,"journal":"Colloids and surfaces. B, Biointerfaces, 228, 113420","doi":"10.1016/j.colsurfb.2023.113420","pmid":"37379702","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07343","title":"Natriuretic Peptides as Biomarkers: Narrative Review and Considerations in Cardiovascular and Respiratory Dysfunctions.","authors":"Samad, Mohammad; Malempati, Sreekar; Restini, Carolina B A","year":2023,"journal":"The Yale journal of biology and medicine, 96(1), 137-149","doi":"10.59249/NCST6937","pmid":"37009194","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07344","title":"Retrospective Analysis of Hospitalized Patients with Type 2 Diabetes Mellitus Treated with Glucagon-Like Peptide 1 Receptor Agonist Therapy.","authors":"San, Khaingthazin; Fogel, Joshua; Khazron, Dmitriy","year":2023,"journal":"Southern medical journal, 116(2), 231-236","doi":"10.14423/SMJ.0000000000001511","pmid":"36724541","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07345","title":"Natriuretic peptide pathways in heart failure: further therapeutic possibilities.","authors":"Sangaralingham, S Jeson; Kuhn, Michaela; Cannone, Valentina; Chen, Horng H; Burnett, John C","year":2023,"journal":"Cardiovascular research, 118(18), 3416-3433","doi":"10.1093/cvr/cvac125","pmid":"36004816","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07346","title":"The common HLA class I-restricted tumor-infiltrating T cell response in HPV16-induced cancer.","authors":"Santegoets, Saskia J; Welters, Marij J P; Schrikkema, Deborah S; Freriks, Manon R; Kok, Hanna; Weissbrich, Bianca; van den Branden, Anouk; Linnemann, Carsten; Schumacher, Ton N; Adhikary, Sabina; Bendle, Gavin; van der Burg, Sjoerd H","year":2023,"journal":"Cancer immunology, immunotherapy : CII, 72(6), 1553-1565","doi":"10.1007/s00262-022-03350-x","pmid":"36526910","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Using multimer staining and a functional screening platform with single HLA-engineered antigen presenting cells, researchers detected 20 CD8+ T cell responses to 11 different endogenously processed HLA-peptide combinations across 12 HPV16-induced tumors. Specific HLA-peptide combinations dominated responses in patients expressing those HLA alleles.\n\nT cell receptors (TCRs) reactive to seven different HLA class I-restricted peptides were isolated. Five of six analyzed TCRs showed tumor reactivity, confirming they recognize naturally processed and presented peptides on actual tumor cells. These TCRs could potentially be used for adoptive cell transfer immunotherapy.","whyItMatters":"HPV16-caused cancers affect hundreds of thousands of people annually worldwide. While preventive vaccines exist, treatments for established HPV cancers are needed. Knowing exactly which viral peptides the immune system targets allows development of therapeutic vaccines and engineered T cell therapies. The identified tumor-reactive TCRs could be manufactured into off-the-shelf T cell therapies for patients whose immune systems aren't fighting the cancer effectively on their own.","specificNumbers":"","methodology":"Tumor-infiltrating lymphocytes from 12 HPV16-induced tumors were screened using HLA-peptide multimers and a functional platform using single HLA class I allele-engineered antigen presenting cells. This approach identified CD8+ T cell epitopes without prior assumptions about which peptides would be presented. Reactive T cell receptors were isolated and tested for tumor cell killing activity.","limitations":"The study included only 12 tumors, limiting the completeness of the epitope map. HLA diversity means some rare HLA alleles may not have been represented. TCR reactivity was confirmed for most but not all isolated receptors. The study was performed in vitro — clinical efficacy of these TCRs in adoptive cell therapy has not been demonstrated. Tumor heterogeneity and immune evasion mechanisms could limit therapeutic effectiveness in vivo."},{"rthcId":"RPEP-07347","title":"Effects of exenatide on coronary stent's endothelialization in subjects with type 2 diabetes: a randomized controlled trial. The Rebuild study.","authors":"Santos-Pardo, Irene; Witt, Nils; Angerås, Oskar; Nyström, Thomas","year":2023,"journal":"Cardiovascular diabetology, 22(1), 337","doi":"10.1186/s12933-023-02071-4","pmid":"38066597","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07348","title":"Evaluation of Anti-Oxinflammatory and ACE-Inhibitory Properties of Protein Hydrolysates Obtained from Edible Non-Mulberry Silkworm Pupae (Antheraea assama and Philosomia ricinii).","authors":"Sarkar, Preeti; Pecorelli, Alessandra; Woodby, Brittany; Pambianchi, Erika; Ferrara, Francesca; Duary, Raj Kumar; Valacchi, Giuseppe","year":2023,"journal":"Nutrients, 15(4)","doi":"10.3390/nu15041035","pmid":"36839393","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07349","title":"Cerebrolysin reduces excitotoxicity by modulation of cell-death proteins in delayed hours of ischemic reperfusion injury.","authors":"Sarode, Lopmudra P; Ghatage, Trupti; Mardhekar, Vishal; Verma, Bhavesh; Prakash, Anand; Ugale, Rajesh R","year":2023,"journal":"Metabolic brain disease, 38(7), 2401-2416","doi":"10.1007/s11011-023-01240-4","pmid":"37273080","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07350","title":"Thymus-derived hormonal and cellular control of cancer.","authors":"Savino, Wilson; Lepletier, Ailin","year":2023,"journal":"Frontiers in endocrinology, 14, 1168186","doi":"10.3389/fendo.2023.1168186","pmid":"37529610","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07351","title":"Tolerability, safety and pharmacodynamics of oral, small-molecule glucagon-like peptide-1 receptor agonist danuglipron for type 2 diabetes: A 12-week, randomized, placebo-controlled, Phase 2 study comparing different dose-escalation schemes.","authors":"Saxena, Aditi R; Frias, Juan P; Gorman, Donal N; Lopez, Rene N; Andrawis, Nabil; Tsamandouras, Nikolaos; Birnbaum, Morris J","year":2023,"journal":"Diabetes, obesity & metabolism, 25(10), 2805-2814","doi":"10.1111/dom.15168","pmid":"37311722","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07352","title":"Kidney function loss and albuminuria progression with GLP-1 receptor agonists versus basal insulin in patients with type 2 diabetes: real-world evidence.","authors":"Schechter, Meir; Melzer Cohen, Cheli; Fishkin, Alisa; Rozenberg, Aliza; Yanuv, Ilan; Sehtman-Shachar, Dvora R; Chodick, Gabriel; Clark, Alice; Abrahamsen, Trine J; Lawson, Jack; Karasik, Avraham; Mosenzon, Ofri","year":2023,"journal":"Cardiovascular diabetology, 22(1), 126","doi":"10.1186/s12933-023-01829-0","pmid":"37244998","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07353","title":"Dual GIP/GLP-1 receptor agonists: New advances for treating type-2 diabetes.","authors":"Scheen, André J","year":2023,"journal":"Annales d'endocrinologie, 84(2), 316-321","doi":"10.1016/j.ando.2022.12.423","pmid":"36639119","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07354","title":"An observational study on monoclonal antibodies against calcitonin-gene-related peptide and its receptor.","authors":"Schiano di Cola, Francesca; Bolchini, Marco; Ceccardi, Giulia; Caratozzolo, Salvatore; Liberini, Paolo; Rao, Renata; Padovani, Alessandro","year":2023,"journal":"European journal of neurology, 30(6), 1764-1773","doi":"10.1111/ene.15761","pmid":"36856538","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07355","title":"Substance P and Prokineticin-2 are overexpressed in olfactory neurons and play differential roles in persons with persistent post-COVID-19 olfactory dysfunction.","authors":"Schirinzi, Tommaso; Lattanzi, Roberta; Maftei, Daniela; Grillo, Piergiorgio; Zenuni, Henri; Boffa, Laura; Albanese, Maria; Simonetta, Clara; Bovenzi, Roberta; Maurizi, Riccardo; Loccisano, Laura; Vincenzi, Martina; Greco, Antonio; Di Girolamo, Stefano; Mercuri, Nicola B; Passali, Francesco M; Severini, Cinzia","year":2023,"journal":"Brain, behavior, and immunity, 108, 302-308","doi":"10.1016/j.bbi.2022.12.017","pmid":"36549578","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07356","title":"Copeptin, Natriuretic Peptides, and Cardiovascular Outcomes in Patients With CKD: The German Chronic Kidney Disease (GCKD) Study.","authors":"Schneider, Markus P; Schmid, Matthias; Nadal, Jennifer; Krane, Vera; Saritas, Turgay; Busch, Martin; Schultheiss, Ulla T; Meiselbach, Heike; Friedrich, Nele; Nauck, Matthias; Floege, Jürgen; Kronenberg, Florian; Wanner, Christoph; Eckardt, Kai-Uwe","year":2023,"journal":"Kidney medicine, 5(11), 100725","doi":"10.1016/j.xkme.2023.100725","pmid":"37915964","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07357","title":"Randomized, Double-Blind, Placebo-Controlled Trial of MUC1 Peptide Vaccine for Prevention of Recurrent Colorectal Adenoma.","authors":"Schoen, Robert E; Boardman, Lisa A; Cruz-Correa, Marcia; Bansal, Ajay; Kastenberg, David; Hur, Chin; Dzubinski, Lynda; Kaufman, Sharon F; Rodriguez, Luz M; Richmond, Ellen; Umar, Asad; Szabo, Eva; Salazar, Andres; McKolanis, John; Beatty, Pamela; Pai, Reetesh K; Singhi, Aatur D; Jacqueline, Camille M; Bao, Riyue; Diergaarde, Brenda; McMurray, Ryan P; Strand, Carrie; Foster, Nathan R; Zahrieh, David M; Limburg, Paul J; Finn, Olivera J","year":2023,"journal":"Clinical cancer research : an official journal of the American Association for Cancer Research, 29(9), 1678-1688","doi":"10.1158/1078-0432.CCR-22-3168","pmid":"36892581","tags":[],"studyType":"randomized controlled trial","evidenceStrength":"high","keyFinding":"In this double-blind, placebo-controlled trial, the MUC1 peptide vaccine successfully generated immune responses in 25% of recipients (13/52) — significantly more than placebo (0/50, p < 0.0001). However, the overall adenoma recurrence rate was not significantly different between vaccine (56.3%) and placebo (66.0%) groups (adjusted RR 0.83, p = 0.25). The most intriguing finding was among the subset who mounted a robust immune response at both 12 and 55 weeks: only 27.3% (3/11) developed recurrent adenomas versus 66% in the placebo group — a 38% absolute reduction (adjusted RR 0.41, p = 0.08). The vaccine showed no difference in serious adverse events compared to placebo.","whyItMatters":"This is one of the first randomized controlled trials testing a peptide vaccine to prevent precancerous colon polyps (adenomas) from coming back — a cancer prevention strategy rather than cancer treatment. While the overall result was negative, the dramatic reduction in adenoma recurrence among strong immune responders (27.3% vs. 66%) suggests the vaccine concept works, but only in people whose immune systems respond robustly. This points toward a future where peptide vaccines might prevent cancer in people who can mount adequate immune responses.","specificNumbers":"n=103 (53 vaccine, 50 placebo) · 25% immune response rate (13/52) · Overall recurrence: 56.3% vs. 66.0% (p=0.25) · Strong responders: 27.3% vs. 66.0% recurrence (p=0.08) · 38% absolute reduction in responders","methodology":"This multicenter, double-blind, placebo-controlled RCT enrolled 103 adults aged 40-70 with a recent advanced colorectal adenoma. Participants received either the MUC1 peptide vaccine or placebo at weeks 0, 2, and 10, with a booster at week 53. The primary endpoint was vaccine immunogenicity (≥2-fold increase in anti-MUC1 IgG at 12 weeks). Secondary endpoints included adenoma recurrence assessed at ≥1 year from randomization.","limitations":"Only 25% of vaccine recipients mounted an immune response, limiting the vaccine's population-level efficacy. The study was small (n=103) and may have been underpowered to detect the overall adenoma reduction as significant. The dramatic result in strong responders (p=0.08) did not reach statistical significance and involved only 11 patients. There is no way to predict in advance who will respond to the vaccine. The study does not explain why 75% of recipients failed to generate an immune response."},{"rthcId":"RPEP-07358","title":"Light It Up! The Use of DOTATATE in Diagnosis and Treatment of Neuroendocrine Neoplasms.","authors":"Schwarz, Jason L; Williams, Jelani K; Keutgen, Xavier M; Liao, Chih-Yi","year":2023,"journal":"Surgical pathology clinics, 16(1), 151-161","doi":"10.1016/j.path.2022.09.013","pmid":"36739162","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Diagnostic 68Ga-DOTATATE PET/CT has demonstrated improved sensitivity in detecting both primary and metastatic neuroendocrine lesions compared to conventional imaging and prior-generation somatostatin receptor imaging methods.\n\nFor treatment, peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE has been validated by prospective randomized controlled studies showing beneficial impact on survival and quality of life. PRRT is now frequently included in the management of neuroendocrine neoplasms. However, the therapy is still considered palliative rather than curative and may be accompanied by adverse effects.","whyItMatters":"DOTATATE represents one of the most elegant applications of peptide science in medicine: the same peptide molecule serves as both a diagnostic tool and a therapeutic agent simply by changing which radioactive isotope is attached. This 'theranostic' approach — diagnose and treat with the same targeting molecule — is a model for precision oncology. For patients with neuroendocrine tumors, which were historically difficult to detect and had limited treatment options, DOTATATE has been transformative.","specificNumbers":"","methodology":"This is a review article published in Surgical Pathology Clinics summarizing the current evidence for DOTATATE-based diagnostics (68Ga-DOTATATE PET/CT) and therapeutics (177Lu-DOTATATE PRRT) in neuroendocrine neoplasms. The review synthesizes data from prospective randomized controlled trials and clinical experience.","limitations":"The abstract is brief and does not provide specific numerical data from the referenced clinical trials. PRRT with 177Lu-DOTATATE is explicitly noted as palliative rather than curative, and adverse effects can occur. Not all neuroendocrine tumors express sufficient somatostatin receptors for DOTATATE to be effective. Patient selection, optimal sequencing with other therapies, and long-term toxicity profiles remain areas of ongoing research."},{"rthcId":"RPEP-07359","title":"Real-world persistence and costs among patients with chronic migraine treated with onabotulinumtoxinA or calcitonin gene-related peptide monoclonal antibodies.","authors":"Schwedt, Todd J; Lee, Jae; Knievel, Kerry; McVige, Jennifer; Wang, Weiying; Wu, Zheng; Gillard, Patrick; Shah, Darshini; Blumenfeld, Andrew M","year":2023,"journal":"Journal of managed care & specialty pharmacy, 29(10), 1119-1128","doi":"10.18553/jmcp.2023.29.10.1119","pmid":"37776119","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07360","title":"Multifunctional Self-Assembled Peptide Hydrogels for Biomedical Applications.","authors":"Sedighi, Mahsa; Shrestha, Neha; Mahmoudi, Zahra; Khademi, Zahra; Ghasempour, Alireza; Dehghan, Hamideh; Talebi, Seyedeh Fahimeh; Toolabi, Maryam; Préat, Véronique; Chen, Bozhi; Guo, Xindong; Shahbazi, Mohammad-Ali","year":2023,"journal":"Polymers, 15(5)","doi":"10.3390/polym15051160","pmid":"36904404","tags":[],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Self-assembled peptide hydrogels represent a versatile class of biomaterials with applications spanning drug delivery, tissue engineering, cancer therapy, stem cell therapy, bioimaging, and regenerative medicine. Their biocompatibility, biodegradability, and ability to mimic natural tissue microenvironments make them particularly promising for targeted and stimulus-responsive drug release systems.\n\nThe review highlights that peptide hydrogels can be designed to respond to both internal stimuli (pH, enzymes, redox conditions) and external stimuli (temperature, light, ultrasound) for controlled therapeutic release. Key structural forms include micelles, hydrogels, and vesicles, each offering distinct advantages for specific biomedical applications.","whyItMatters":"Peptide hydrogels bridge the gap between synthetic drug delivery systems and biological tissues. Their ability to self-assemble from simple building blocks using scalable, inexpensive methods could democratize access to advanced therapeutic platforms. This review maps the current landscape of what these materials can do across multiple medical fields.","specificNumbers":"","methodology":"Comprehensive literature review examining recent advances in the design, fabrication, and biomedical applications of self-assembled peptide hydrogels, covering their chemical, physical, and biological properties.","limitations":"As a review article, this paper synthesizes existing research rather than presenting new experimental data. The breadth of coverage means individual applications are not explored in exhaustive depth."},{"rthcId":"RPEP-07361","title":"Differences in weight loss and safety between the glucagon-like peptide-1 receptor agonists: A non-randomized multicenter study from the titration phase.","authors":"Seijas-Amigo, José; Salgado-Barreira, Ángel; Castelo-Dominguez, Rosana; Pérez-Álvarez, María Teresa; Ponce-Piñón, Belén; Fernández-Silva, Marlén; Rodríguez-Barreiro, Marta; Pereira-Pía, Mercedes; Iglesias-Moreno, Jose Manuel; Gago-García, Mar; Montáns-García, Raquel; Fernandez-Perez, Agustina; FragaGayoso, Dolores; Fernandez-Montenegro, Montse; Riveiro-Barciela, Beatriz; Rilla-Villar, Natalia; Cordero, Alberto; RodríguezMañero, Moisés; González-Juanatey, José R","year":2023,"journal":"Primary care diabetes, 17(4), 366-372","doi":"10.1016/j.pcd.2023.05.004","pmid":"37230813","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07362","title":"A Peptide in a Pill - Oral Semaglutide in the Management of Type 2 Diabetes.","authors":"Selvarajan, Raja; Subramanian, Rashmi","year":2023,"journal":"Diabetes, metabolic syndrome and obesity : targets and therapy, 16, 1709-1720","doi":"10.2147/DMSO.S385196","pmid":"37312901","tags":["glp-1-agonists","oral-peptide-delivery","type-2-diabetes"],"studyType":"review","evidenceStrength":"review-narrative","keyFinding":"This review covers oral semaglutide (Rybelsus), the first GLP-1 receptor agonist available as a pill rather than an injection. The drug combines semaglutide with SNAC (sodium N-[8-(2-hydroxybenzoyl) amino] caprylate), an absorption enhancer that helps the peptide cross the stomach lining intact.\n\nBeyond blood sugar control, the review highlights that GLP-1 receptor agonists deliver significant weight loss with low hypoglycemia risk, reduce major adverse cardiovascular events, and may protect the kidneys in patients with type 2 diabetes and chronic kidney disease. Clinical trials have shown GLP-1 RA treatment is safe and tolerated in patients with impaired renal function.","whyItMatters":"Peptide drugs traditionally require injection because stomach acid destroys them. Oral semaglutide solved this with SNAC technology, making GLP-1 therapy more accessible to patients who resist daily or weekly injections. This matters because adherence is a major barrier in diabetes management, and an oral option could help more patients benefit from the cardiovascular and kidney-protective effects of GLP-1 drugs.","specificNumbers":"Oral formulation uses SNAC absorption enhancer · GLP-1 RAs reduce major adverse cardiovascular events · Safe in patients with CKD · Lower hypoglycemia risk than many diabetes drugs","methodology":"Narrative review summarizing the pharmacology of oral semaglutide, the SNAC absorption technology, and clinical evidence from large trials (primarily cardiovascular outcome trials) on the efficacy and safety of GLP-1 receptor agonists in type 2 diabetes.","limitations":"This is a narrative review, not a systematic review or meta-analysis. It does not present new clinical data. The review focuses primarily on oral semaglutide's advantages without deeply comparing it to injectable formulations or newer dual/triple agonists that were in development at the time."},{"rthcId":"RPEP-07363","title":"Stapled β-Hairpin Antimicrobial Peptides with Improved Stability and Activity against Drug-Resistant Gram-Negative Bacteria.","authors":"Selvarajan, Vanitha; Tram, Nhan D T; Xu, Jian; Ngen, Sarah T Y; Koh, Jun-Jie; Teo, Jeanette W P; Yuen, Tsz-Ying; Ee, Pui Lai Rachel","year":2023,"journal":"Journal of medicinal chemistry, 66(13), 8498-8509","doi":"10.1021/acs.jmedchem.3c00140","pmid":"37357499","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07364","title":"Discrete Choice Experiment to Understand Japanese Patients' and Physicians' Preferences for Preventive Treatments for Migraine.","authors":"Seo, Jaein; Tervonen, Tommi; Ueda, Kaname; Zhang, Dian; Danno, Daisuke; Tockhorn-Heidenreich, Antje","year":2023,"journal":"Neurology and therapy, 12(2), 651-668","doi":"10.1007/s40120-023-00453-0","pmid":"36848008","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07365","title":"Effects of once-weekly dulaglutide on juvenile type 2 diabetes mellitus and obesity in Korea: a pilot study.","authors":"Seo, Ji Young; Lee, Cha Gon; Choi, Hoonsung; Lee, Hong Kyu; Lee, So Young; Kim, Hyo-Jeong; Jung, Kyong Yeun; Kim, Jin Taek","year":2023,"journal":"Annals of pediatric endocrinology & metabolism, 28(4), 296-301","doi":"10.6065/apem.2244196.098","pmid":"36758973","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07366","title":"First Reported Case of Dulaglutide-Induced Acute Pancreatitis With Normal Serum Lipase Level.","authors":"Shahbazi, Mohammad; Qudsiya, Zainab; Fahel, Aboud; Amini, Afshin; Tanoli, Tariq","year":2023,"journal":"Cureus, 15(6), e40576","doi":"10.7759/cureus.40576","pmid":"37465801","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07367","title":"Resveratrol and Dulaglutide ameliorate adiposity and liver dysfunction in rats with diet-induced metabolic syndrome: Role of SIRT-1 / adipokines / PPARγ and IGF-1.","authors":"Shamardl, Hanan Abdel Moneam A; Ibrahim, Noha A; Merzeban, Dina H; Elamir, Azza M; Golam, Rehab M; Elsayed, Asmaa M","year":2023,"journal":"Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences, 31(1), 13-27","doi":"10.1007/s40199-023-00458-y","pmid":"36991247","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07368","title":"Pilot study to test the safety, tolerability and feasibility of dulaglutide during a low-energy diet for weight loss and improved glycaemic control.","authors":"Shand, James Allan Douglas; Young, Simon; Verster, Francois; Peters, Carl","year":2023,"journal":"BMJ nutrition, prevention & health, 6(2), 341-346","doi":"10.1136/bmjnph-2023-000733","pmid":"38264361","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07369","title":"Ultrashort All-Hydrocarbon Stapled α-Helix Amphiphile as a Potent and Stable Antimicrobial Compound.","authors":"Shao, Changxuan; Jian, Qiao; Li, Bowen; Zhu, Yongjie; Yu, Weikang; Li, Zhongyu; Shan, Anshan","year":2023,"journal":"Journal of medicinal chemistry, 66(16), 11414-11427","doi":"10.1021/acs.jmedchem.3c00856","pmid":"37531494","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07370","title":"Identification and Characterization of Novel ACE Inhibitory and Antioxidant Peptides from Sardina pilchardus Hydrolysate.","authors":"Shao, Mingyang; Wu, Haixing; Wang, Bohui; Zhang, Xuan; Gao, Xia; Jiang, Mengqi; Su, Ruiheng; Shen, Xuanri","year":2023,"journal":"Foods (Basel, Switzerland), 12(11)","doi":"10.3390/foods12112216","pmid":"37297461","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Sardina pilchardus protein hydrolysate (SPH) produced using dispase and alkaline protease yielded peptide fractions with ACE inhibitory activity, with the low molecular mass fractions showing the strongest effects. The peptides also exhibited antioxidant properties.\n\nUsing LC-MS/MS combined with online database searching and molecular docking, the researchers identified novel peptide sequences with strong predicted binding to the ACE enzyme. The dual functionality — both ACE inhibition and antioxidant activity — makes these peptides particularly interesting for functional food development targeting cardiovascular health.","whyItMatters":"High blood pressure is a leading risk factor for heart disease and stroke. While ACE inhibitor drugs are effective, they can have side effects. Food-derived ACE inhibitory peptides offer a natural alternative that could be incorporated into functional foods or supplements. Sardines are inexpensive and widely available, making them a practical source for these bioactive peptides. The combined ACE inhibitory and antioxidant properties address multiple cardiovascular risk factors simultaneously.","specificNumbers":"","methodology":"Sardine (Sardina pilchardus) proteins were hydrolyzed using dispase and alkaline protease enzymes. The hydrolysate was fractionated by molecular weight. ACE inhibitory activity and antioxidant capacity were measured for each fraction. LC-MS/MS (liquid chromatography-tandem mass spectrometry) was used to identify individual peptide sequences. Molecular docking simulations modeled the binding interactions between identified peptides and the ACE enzyme to predict and explain their inhibitory activity.","limitations":"This is entirely an in vitro and computational study — no animal or human testing was performed. The abstract is incomplete (appears truncated), making it difficult to assess the full scope of results. Specific peptide sequences, IC50 values for ACE inhibition, and antioxidant assay results are not provided in the available abstract. The stability of these peptides during digestion and their bioavailability after oral consumption are unknown. Clinical blood pressure effects would need to be demonstrated in human trials."},{"rthcId":"RPEP-07371","title":"Delivery of Active Peptides by Self-Healing, Biocompatible and Supramolecular Hydrogels.","authors":"Shariati Pour, Seyedeh Rojin; Oddis, Sara; Barbalinardo, Marianna; Ravarino, Paolo; Cavallini, Massimiliano; Fiori, Jessica; Giuri, Demetra; Tomasini, Claudia","year":2023,"journal":"Molecules (Basel, Switzerland), 28(6)","doi":"10.3390/molecules28062528","pmid":"36985499","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07372","title":"Peptide-based drug discovery: Current status and recent advances.","authors":"Sharma, Komal; Sharma, Krishna K; Sharma, Anku; Jain, Rahul","year":2023,"journal":"Drug discovery today, 28(2), 103464","doi":"10.1016/j.drudis.2022.103464","pmid":"36481586","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07373","title":"Short Antimicrobial Peptides: Therapeutic Potential and Recent Advancements.","authors":"Sharma, Lalita; Bisht, Gopal Singh","year":2023,"journal":"Current pharmaceutical design, 29(38), 3005-3017","doi":"10.2174/0113816128248959231102114334","pmid":"38018196","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07374","title":"Corn distillers solubles by two-step proteolytic hydrolysis as a new source of plant-based protein hydrolysates with ACE and DPP4 inhibition activities.","authors":"Sharma, Sonu; Pradhan, Ranjan; Manickavasagan, Annamalai; Tsopmo, Apollinaire; Thimmanagari, Mahendra; Dutta, Animesh","year":2023,"journal":"Food chemistry, 401, 134120","doi":"10.1016/j.foodchem.2022.134120","pmid":"36096002","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Two-step enzymatic hydrolysis of corn distillers solubles (CDS) protein using alcalase followed by flavourzyme (AF) produced peptides with 97.68% ACE inhibition and 51.51% DPP4 inhibition — the highest dual bioactivity among all hydrolysis combinations tested. Nine novel peptides were identified by mass spectrometry from the most active fraction (<3 kDa), including APLA, PLFP, LFLP, LPPYL, PLYPLP, NDWHTGPL, LPPYLPS, GSPFLGQ, and SWQQPIVGG. Bioinformatic analysis confirmed these peptides can bind to the active sites of both ACE and DPP4 enzymes.","whyItMatters":"Corn distillers solubles are a low-value byproduct of ethanol production that is largely underutilized. Finding that these waste proteins can be converted into peptides with dual blood pressure-lowering (ACE inhibition) and blood sugar-regulating (DPP4 inhibition) activity transforms industrial waste into a potential source of functional food ingredients. This approach adds value to agricultural byproducts while addressing two of the most prevalent chronic diseases — hypertension and type 2 diabetes.","specificNumbers":"97.68% ACE inhibition · 51.51% DPP4 inhibition · 9 novel peptides identified · <3 kDa active fraction · 6 hydrolysis combinations tested","methodology":"Laboratory study comparing one-step (alcalase, trypsin, or flavourzyme alone) and two-step (6 sequential combinations) enzymatic hydrolysis of CDS proteins. Hydrolysates were evaluated for yield, protein content, degree of hydrolysis, ACE inhibition, and DPP4 inhibition. The most active hydrolysate (AF, alcalase then flavourzyme) was fractionated to <3 kDa and analyzed by mass spectrometry to identify peptide sequences. Bioinformatic analysis and molecular docking assessed peptide binding to ACE and DPP4 active sites.","limitations":"This is entirely an in vitro and computational study — no animal or human testing was performed. The inhibitory activities measured in test tubes may not translate to actual blood pressure or blood sugar effects in the body, as peptides must survive digestion and reach their targets. Bioavailability and stability of these peptides in the gastrointestinal tract were not assessed."},{"rthcId":"RPEP-07375","title":"Advances in Computational and Bioinformatics Tools and Databases for Designing and Developing a Multi-Epitope-Based Peptide Vaccine.","authors":"Shawan, Mohammad Mahfuz Ali Khan; Sharma, Ashish Ranjan; Halder, Sajal Kumar; Arian, Tawsif Al; Shuvo, Md Nazmussakib; Sarker, Satya Ranjan; Hasan, Md Ashraful","year":2023,"journal":"International journal of peptide research and therapeutics, 29(4), 60","doi":"10.1007/s10989-023-10535-0","pmid":"37251529","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07376","title":"Design of experiments approach for the development of a validated method to determine the exenatide content in poly(lactide-co-glycolide) microspheres.","authors":"Sheikhi, Mojgan; Sharifzadeh, Mohammad; Hennink, Wim E; Firoozpour, Loghman; Hajimahmoodi, Mannan; Khoshayand, Mohammad Reza; Shirangi, Mehrnoosh","year":2023,"journal":"European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 192, 56-61","doi":"10.1016/j.ejpb.2023.09.016","pmid":"37783361","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07377","title":"Caveolin-1-Related Intervention for Fibrotic Lung Diseases.","authors":"Shetty, Sreerama; Idell, Steven","year":2023,"journal":"Cells, 12(4)","doi":"10.3390/cells12040554","pmid":"36831221","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07378","title":"Sustained release of alginate hydrogel containing antimicrobial peptide Chol-37(F34-R) in vitro and its effect on wound healing in murine model of Pseudomonas aeruginosa infection.","authors":"Shi, Shuaibing; Dong, Hefan; Chen, Xiaoyou; Xu, Siqi; Song, Yue; Li, Meiting; Yan, Zhiling; Wang, Xiaoli; Niu, Mingfu; Zhang, Min; Liao, Chengshui","year":2023,"journal":"Journal of veterinary science, 24(3), e44","doi":"10.4142/jvs.22319","pmid":"37271512","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07379","title":"Effects of Aerobic Exercise Combined with Oyster Peptide Supplement on the Formation of CTX-induced Late-Onset Hypogonadism in Male Rats.","authors":"Shi, Wenting; Liu, Yu; Jin, Qiguan; Wu, Meitong; Sun, Qizheng; Li, Zheng; Liu, Wenying","year":2023,"journal":"Reproductive sciences (Thousand Oaks, Calif.), 30(4), 1291-1305","doi":"10.1007/s43032-022-01068-w","pmid":"36097247","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CTX-induced hypogonadism decreased LH, total and free testosterone, androgen receptor, androgen binding protein, and GSH-Px while increasing oxidative stress markers and impairing sexual behavior. Aerobic exercise combined with oyster peptide supplementation significantly reversed all these changes except serum LH. The combination was superior to exercise alone for serum total testosterone, FSH, testicular testosterone, mating latency, capture times, and mating times. Steroidogenic gene expression (StAR, P450scc, StARD7) was rescued by the combination treatment.","whyItMatters":"Late-onset hypogonadism affects a significant proportion of aging men and can be exacerbated by medications and chronic conditions. While testosterone replacement therapy carries risks, finding natural approaches like exercise and bioactive peptide supplements that support endogenous testosterone production could offer safer alternatives. Oyster peptides — rich in zinc and specific amino acid sequences — may provide nutritional support for testicular function through antioxidant and endocrine-modulatory mechanisms.","specificNumbers":"","methodology":"Male Sprague-Dawley rats received low-dose cyclophosphamide (CTX) to induce late-onset hypogonadism. Groups received 6 weeks of aerobic exercise training, oyster peptide supplementation, both combined, or neither. Researchers measured serum hormones (LH, TT, FT, FSH), testicular hormones and proteins (TT, AR, ABP), oxidative stress markers (GSH-Px, MDA), sexual behavior parameters (mating times, latency, capture), and steroidogenic gene expression (StAR, P450scc, StARD7) by RT-qPCR.","limitations":"This is a rat study using chemically-induced hypogonadism, which differs from natural age-related testosterone decline in humans. The specific oyster peptide composition was not detailed, making it difficult to identify active components. The 6-week duration is relatively short. The CTX model may not represent the gradual onset of natural LOH. No dose-response relationship was established for the oyster peptide. Human clinical trials would be needed to validate these findings."},{"rthcId":"RPEP-07380","title":"Three-dimensional Culture Using Atelocollagen Sponge and Self-assembling Peptide Hydrogel.","authors":"Shiga, Takeaki; Kato, Hiroshi; Saito, Akiko; Onodera, Shoko; Shibahara, Takahiko; Takano, Masayuki; Azuma, Toshifumi","year":2023,"journal":"The Bulletin of Tokyo Dental College, 64(2), 43-54","doi":"10.2209/tdcpublication.2022-0027","pmid":"37183012","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07381","title":"Antimicrobial peptide cathelicidin LL-37 preserves intestinal barrier and organ function in rats with heat stroke.","authors":"Shih, Chih-Chin; Liao, Wei-Chieh; Ke, Hung-Yen; Kuo, Chia-Wen; Tsao, Cheng-Ming; Tsai, Wen-Chiuan; Chiu, Yi-Lin; Huang, Hsieh-Chou; Wu, Chin-Chen","year":2023,"journal":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 161, 114565","doi":"10.1016/j.biopha.2023.114565","pmid":"36958193","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07382","title":"Effect of sacubitril/valsartan on natriuretic peptide in patients with compensated heart failure.","authors":"Shirakabe, Akihiro; Matsushita, Masato; Sawatani, Tomofumi; Noma, Satsuki; Takayasu, Tsutomu; Kanai, Hideki; Asano, Miwako; Nomura, Akiko; Asai, Kuniya","year":2023,"journal":"Heart and vessels, 38(6), 773-784","doi":"10.1007/s00380-022-02230-9","pmid":"36656354","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Sacubitril/valsartan treatment significantly increased atrial natriuretic peptide (ANP) levels in patients with compensated heart failure — from a median of 102 pg/mL at baseline to 283 pg/mL at 3 months and 409 pg/mL at 6 months. Simultaneously, the daily furosemide (loop diuretic) dose was cut in half, from 40 mg to 20 mg. No such changes occurred in the ACE inhibitor comparison group.\n\nPatients with preserved ejection fraction (HFpEF) and persistent atrial fibrillation showed the largest ANP increases, with odds ratios of 7.558 and 4.649 respectively for high ANP elevation.","whyItMatters":"Natriuretic peptides are the heart's own protective hormones — they lower blood pressure, reduce fluid retention, and protect against cardiac stress. Sacubitril works by blocking neprilysin, the enzyme that breaks down these peptides. This study shows that blocking neprilysin measurably raises ANP levels and allows patients to reduce their diuretic doses, suggesting a shift from artificial fluid management to the body's own peptide-driven system.","specificNumbers":"ANP: 102→283→409 pg/mL; furosemide: 40→20 mg; OR 7.558 for HFpEF; OR 4.649 for persistent AF","methodology":"Prospective observational study comparing 42 outpatients with compensated heart failure receiving sacubitril/valsartan to 39 patients on ACE inhibitors, with natriuretic peptide levels and diuretic doses measured at baseline, 3 months, and 6 months.","limitations":"Non-randomized observational design means the two groups may differ in unmeasured ways. The sample size of 81 patients is modest. The study focused on an Asian cohort, which may limit generalizability to other populations."},{"rthcId":"RPEP-07383","title":"Segregation analysis identifies specific alpha-defensin (DEFA1A3) SNP-CNV haplotypes in predisposition to IgA nephropathy.","authors":"Shwan, Nzar A A; Moise, Eric C; Necsoiu, Paula E; Farr, Amy J; Gale, Daniel P; Barratt, Jonathan; Armour, John A L","year":2023,"journal":"Annals of human genetics, 87(1-2), 1-8","doi":"10.1111/ahg.12481","pmid":"36214424","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07384","title":"Substance P aggravates ligature-induced periodontitis in mice.","authors":"Siddiqui, Yasir Dilshad; Nie, Xuguang; Wang, Sheng; Abbasi, Yasaman; Park, Lauren; Fan, Xiaoxuan; Thumbigere-Math, Vivek; Chung, Man-Kyo","year":2023,"journal":"Frontiers in immunology, 14, 1099017","doi":"10.3389/fimmu.2023.1099017","pmid":"37122730","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07385","title":"Mechanical bacterial lysate enhances antimicrobial barrier mechanisms in human airway epithelial cells.","authors":"Sidoti Migliore, Giacomo; Campana, Stefania; Barberi, Chiara; De Pasquale, Claudia; Pezzino, Gaetana; Cavaliere, Riccardo; Orecchia, Paola; Ginestra, Giovanna; Mandalari, Giuseppina; Del Zotto, Genny; Bonaccorsi, Irene; Carrega, Paolo; Mingari, Maria Cristina; Ferlazzo, Guido","year":2023,"journal":"Journal of leukocyte biology, 113(5), 535-540","doi":"10.1093/jleuko/qiad003","pmid":"36807710","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07386","title":"A physiologically based pharmacokinetic model for [68Ga]Ga-(HA-)DOTATATE to predict whole-body distribution and tumor sink effects in GEP-NET patients.","authors":"Siebinga, Hinke; de Wit-van der Veen, Berlinda J; Beijnen, Jos H; Dorlo, Thomas P C; Huitema, Alwin D R; Hendrikx, Jeroen J M A","year":2023,"journal":"EJNMMI research, 13(1), 8","doi":"10.1186/s13550-023-00958-7","pmid":"36735114","tags":["peptide-imaging","somatostatin-analogs"],"studyType":"modeling-study","evidenceStrength":"moderate","keyFinding":"Researchers built a physiologically based pharmacokinetic (PBPK) model that accurately predicts how two gallium-68-labeled somatostatin peptides — DOTATATE and HA-DOTATATE — distribute through the body and into tumors of neuroendocrine cancer patients. Key findings: the uptake differences between the two peptides in organs were driven by their different receptor binding affinities, while tumor uptake was primarily determined by tumor blood flow and blood volume. The 'tumor sink effect' — where large tumors absorb so much peptide that normal organs get less — was only clinically relevant when total tumor volume exceeded about 550 mL, which affects a minority of patients.","whyItMatters":"Gallium-68 DOTATATE PET scans are the gold standard for diagnosing and staging neuroendocrine tumors. This model helps clinicians understand why scan results vary between patients and between the two peptide tracers. Knowing that tumor sink only matters above 550 mL of tumor volume provides practical guidance for interpreting scans in patients with high tumor burden.","specificNumbers":"n=98 patients total · 39 received DOTATATE · 59 received HA-DOTATATE · Tumor sink relevant above ~550 mL tumor volume","methodology":"The team developed a PBPK model incorporating receptor binding, internalization, recycling, renal clearance, and intracellular degradation. Three tumor compartments (primary, liver metastases, other metastases) were included. The model was validated against PET scan data from 98 GEP-NET patients and used for tumor sink simulations with increasing tumor volumes.","limitations":"This is a modeling study — predictions are based on mathematical simulations validated against imaging data, not direct measurements of tissue peptide concentrations. The model assumptions about receptor density, binding kinetics, and tumor vascularity may not capture all patient-to-patient variability. The study focused specifically on gastroenteropancreatic NETs; applicability to other NET types is uncertain."},{"rthcId":"RPEP-07387","title":"From Selye's and Szabo's Cysteamine-Duodenal Ulcer in Rats to Dopamine in the Stomach: Therapy Significance and Possibilities.","authors":"Sikiric, Predrag; Boban Blagaic, Alenka; Krezic, Ivan; Zizek, Helena; Kalogjera, Luka; Smoday, Ivan Maria; Vukovic, Vlasta; Oroz, Katarina; Chiddenton, Helen Marie; Buric, Sara; Antunovic, Marko; Gojkovic, Slaven; Strbe, Sanja; Skocic, Milena; Sikiric, Suncana; Milavic, Marija; Beketic Oreskovic, Lidija; Kokot, Antonio; Koprivanac, Antun; Dobric, Ivan; Sever, Marko; Staresinic, Mario; Batelja Vuletic, Lovorka; Skrtic, Anita; Seiwerth, Sven","year":2023,"journal":"Pharmaceuticals (Basel, Switzerland), 16(12)","doi":"10.3390/ph16121699","pmid":"38139825","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07388","title":"Stable Gastric Pentadecapeptide BPC 157 May Recover Brain-Gut Axis and Gut-Brain Axis Function.","authors":"Sikiric, Predrag; Gojkovic, Slaven; Krezic, Ivan; Smoday, Ivan Maria; Kalogjera, Luka; Zizek, Helena; Oroz, Katarina; Vranes, Hrvoje; Vukovic, Vlasta; Labidi, May; Strbe, Sanja; Baketic Oreskovic, Lidija; Sever, Marko; Tepes, Marijan; Knezevic, Mario; Barisic, Ivan; Blagaic, Vladimir; Vlainic, Josipa; Dobric, Ivan; Staresinic, Mario; Skrtic, Anita; Jurjevic, Ivana; Boban Blagaic, Alenka; Seiwerth, Sven","year":2023,"journal":"Pharmaceuticals (Basel, Switzerland), 16(5)","doi":"10.3390/ph16050676","pmid":"37242459","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review presents BPC 157 as a peptide with interconnected effects across the brain-gut and gut-brain axes in animal models. Reported findings include:\n\n- Behavioral effects: anxiolytic, anticonvulsive, antidepressant activity, and counteraction of catalepsy and schizophrenia-like symptoms in animal models\n- Muscle effects: healing and function recovery across various muscle injuries, both peripheral and central\n- Cardiovascular effects: counteracted heart failure, arrhythmias, and thrombosis in animal models\n- Organ protection: counteracted encephalopathies, liver and stomach lesions from NSAIDs and insulin, and multiorgan failure from major vessel occlusion\n- Vascular effects: attenuated severe intracranial, portal, and caval hypertensions, and aortal hypotension\n\nThe authors frame these diverse effects as part of a unified network operating through the brain-gut axis.","whyItMatters":"BPC 157 is one of the most widely discussed peptides in the research peptide community, yet virtually all published data comes from a single research group. This review is significant because it represents the most comprehensive summary of BPC 157's proposed mechanisms from its primary investigators, but readers should note the lack of independent replication and the absence of human clinical trial data.","specificNumbers":"","methodology":"This is a narrative review that compiles and synthesizes findings from the Sikiric research group's own published animal studies on BPC 157. It presents results from various rat and animal models across multiple organ systems. No new experimental data is presented, and the review primarily draws from the authors' own body of work.","limitations":"This review draws almost exclusively from the authors' own research, raising concerns about independent verification. All evidence comes from animal models — no human clinical trials are cited. The extraordinary breadth of claimed effects (behavioral, cardiovascular, muscular, hepatic, renal, gastrointestinal) from a single peptide is unusual and warrants independent confirmation. The narrative review format does not apply systematic methodology for evaluating evidence quality."},{"rthcId":"RPEP-07389","title":"Adverse Events Reported with Therapies Targeting the CGRP Pathway During the First 6 Months Post-launch: A Retrospective Analysis Using the FDA Adverse Events Reporting System.","authors":"Silberstein, Stephen D; Reshef, Shoshana; Cohen, Joshua M; Gandhi, Sanjay; Seminerio, Michael; Ramirez Campos, Verena; Kessler, Yoel; Thompson, Stephen F; Blumenfeld, Andrew","year":2023,"journal":"Advances in therapy, 40(2), 445-459","doi":"10.1007/s12325-022-02346-4","pmid":"36350532","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07390","title":"Efficacy, Toxicity, and Prognostic Factors of Re-treatment With [177Lu]Lu-DOTA-TATE in Patients With Progressing Neuroendocrine Tumors: The Experience of a Single Center.","authors":"Silva, Maria Manuel; Canha, Marta; Salazar, Daniela; Neves, João Sergio; Ferreira, Gonçalo; Carvalho, Davide; Duarte, Hugo","year":2023,"journal":"Cureus, 15(10), e47506","doi":"10.7759/cureus.47506","pmid":"38021538","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"After initial PRRT, all 20 patients eventually progressed, with a median progression-free survival (PFS) of 32 months. Upon retreatment (PRRTR), median PFS was 17.5 months (IQR: 7–39 months). At analysis, 15 of 18 evaluable patients had progressed after retreatment, while 3 had stable disease.\n\nThe median overall survival from the first cycle of initial treatment was 66 months (IQR: 65–90). Safety was favorable: no significant kidney or liver toxicity was reported, and hemoglobin levels remained stable. The only notable adverse effect was a statistically significant decrease in platelet count after retreatment (p=0.03). Patients who received two retreatment cycles had significantly longer PFS than those receiving one (p=0.014), and the presence of metastases before retreatment predicted shorter time to progression (p=0.04).","whyItMatters":"Neuroendocrine tumors are relatively rare cancers with limited treatment options, especially after progression on standard therapies. PRRT with Lu-177 DOTATATE has become a valuable treatment, but what happens when patients progress afterward has been a major unanswered question. This study provides real-world evidence that retreatment is viable — giving oncologists and patients another option rather than having to move to less targeted therapies.","specificNumbers":"","methodology":"This was a single-center retrospective observational study spanning nine years. Twenty patients with progressive neuroendocrine tumors who had previously received [177Lu]Lu-DOTA-TATE PRRT and subsequently progressed were retreated with the same therapy. Researchers evaluated progression-free survival, overall survival, toxicity (renal, hepatic, hematological), and prognostic factors associated with outcomes.","limitations":"This was a small (n=20), single-center, retrospective study — the lowest tier of clinical evidence for treatment efficacy. Two patients were lost to follow-up. There was no control group, so it's impossible to know how much of the benefit was due to retreatment versus natural disease course. The retrospective design is subject to selection bias — patients selected for retreatment may have had more favorable disease characteristics. Specific dosing protocols and patient selection criteria were not detailed in the abstract."},{"rthcId":"RPEP-07391","title":"Emerging drugs for the preventive treatment of migraine: a review of CGRP monoclonal antibodies and gepants trials.","authors":"Silvestro, Marcello; Orologio, Ilaria; Siciliano, Mattia; Trojsi, Francesca; Tessitore, Alessandro; Tedeschi, Gioacchino; Russo, Antonio","year":2023,"journal":"Expert opinion on emerging drugs, 28(2), 79-96","doi":"10.1080/14728214.2023.2207819","pmid":"37185047","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07392","title":"Innovative Pre-Clinical Data Using Peptides to Intervene in the Evolution of Pulmonary Fibrosis.","authors":"Simon, Karina Smidt; Coelho, Luísa Coutinho; Veloso, Paulo Henrique de Holanda; Melo-Silva, Cesar Augusto; Morais, José Athayde Vasconcelos; Longo, João Paulo Figueiró; Figueiredo, Florencio; Viana, Leonora; Silva Pereira, Ildinete; Amado, Veronica Moreira; Mortari, Marcia Renata; Bocca, Anamelia Lorenzetti","year":2023,"journal":"International journal of molecular sciences, 24(13)","doi":"10.3390/ijms241311049","pmid":"37446227","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07393","title":"Donanemab in Early Symptomatic Alzheimer Disease: The TRAILBLAZER-ALZ 2 Randomized Clinical Trial.","authors":"Sims, John R; Zimmer, Jennifer A; Evans, Cynthia D; Lu, Ming; Ardayfio, Paul; Sparks, JonDavid; Wessels, Alette M; Shcherbinin, Sergey; Wang, Hong; Monkul Nery, Emel Serap; Collins, Emily C; Solomon, Paul; Salloway, Stephen; Apostolova, Liana G; Hansson, Oskar; Ritchie, Craig; Brooks, Dawn A; Mintun, Mark; Skovronsky, Daniel M","year":2023,"journal":"JAMA, 330(6), 512-527","doi":"10.1001/jama.2023.13239","pmid":"37459141","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07394","title":"Efficacy and Safety of Tirzepatide in Type 2 Diabetes and Obesity Management.","authors":"Sinha, Rachel; Papamargaritis, Dimitris; Sargeant, Jack A; Davies, Melanie J","year":2023,"journal":"Journal of obesity & metabolic syndrome, 32(1), 25-45","doi":"10.7570/jomes22067","pmid":"36750526","tags":["glp-1-agonists"],"studyType":"review","evidenceStrength":"strong","keyFinding":"This review synthesizes the entire SURPASS and SURMOUNT-1 clinical trial programs for tirzepatide. In type 2 diabetes (SURPASS), weekly tirzepatide 5-15 mg reduced HbA1c by 1.87-3.02% and body weight by 5.4-12.9 kg over up to 104 weeks, outperforming semaglutide 1 mg, dulaglutide, insulin degludec, and insulin glargine. It also improved liver fat, blood pressure, lipids, and reduced new-onset macroalbuminuria.\n\nIn obesity without diabetes (SURMOUNT-1), tirzepatide 5-15 mg produced 16.5-22.4% body weight reduction over 72 weeks — weight loss figures that were unprecedented at the time of publication.","whyItMatters":"Tirzepatide was the first drug to combine GLP-1 and GIP receptor activation, and the results were transformative — HbA1c reductions of up to 3% and weight loss exceeding 20% represented a step change in what medication alone could achieve for diabetes and obesity.","specificNumbers":"HbA1c reduction: 1.87-3.02% · Weight loss (T2DM): 5.4-12.9 kg · Weight loss (obesity): 16.5-22.4% · Up to 104 weeks · Beat semaglutide 1 mg head-to-head","methodology":"Narrative review summarizing the SURPASS clinical trial program (multiple phase 3 RCTs in type 2 diabetes including head-to-head comparisons with semaglutide, dulaglutide, and insulin) and the SURMOUNT-1 trial (phase 3 RCT in obesity without diabetes). Covers global and Japanese-specific populations.","limitations":"As a review, this synthesizes existing trial data rather than generating new evidence. Published in early 2023, it covers SURMOUNT-1 but not later SURMOUNT trials or the cardiovascular outcome data. The semaglutide comparison used the 1 mg dose (for diabetes), not the higher 2.4 mg dose used for obesity. Some cardiometabolic benefits are secondary endpoints requiring further confirmatory studies."},{"rthcId":"RPEP-07395","title":"A Review on Genotoxic and Genoprotective Effects of Biologically Active Compounds of Animal Origin.","authors":"Sjakste, Nikolajs; Gajski, Goran","year":2023,"journal":"Toxins, 15(2)","doi":"10.3390/toxins15020165","pmid":"36828477","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies two categories of DNA effects from venom-derived compounds:\n\n**Genotoxic effects (DNA damage):**\n- Venom peptides like mastoparan, melectin, and melittin (from bee and wasp venoms) can bind DNA and produce DNA breaks\n- Crude venoms from jellyfish, scorpions, spiders, and snakes cause DNA damage primarily through cell membrane disruption and subsequent oxidative stress\n- Sponge-derived compounds (avarol, variolin B) and sea squirt-derived trabectedin also bind and damage DNA\n\n**Genoprotective effects:**\n- Certain animal venoms or their components produce protective effects against DNA damage\n- The dual nature (damage vs protection) depends on concentration, target cell type, and specific compound\n\nBoth properties have therapeutic relevance — DNA-damaging ability could be harnessed for anti-cancer drugs, while protective effects could aid in preventing mutations.","whyItMatters":"Venom-derived peptides are a major source of drug candidates — several are already in clinical use. But DNA damage is a serious safety concern that could cause mutations and cancer. This review highlights that genotoxicity testing must be a priority before venom peptides reach clinical use. At the same time, the DNA-damaging properties of certain venom peptides could be intentionally harnessed for cancer treatment, similar to how trabectedin (from sea squirts) is already used as an anti-cancer drug.","specificNumbers":"","methodology":"This is a narrative review synthesizing published research on the genotoxic and genoprotective effects of biologically active compounds derived from animal venoms. Sources include sponges, sea squirts, bees, wasps, jellyfish, scorpions, spiders, and snakes. The review examines both in vitro DNA-binding studies and cellular genotoxicity assays.","limitations":"This is a narrative review with inherent selection bias. Many of the genotoxicity studies cited were performed in vitro under conditions that may not reflect physiological concentrations. The distinction between direct DNA damage and indirect oxidative damage is not always clear in the underlying studies. Most data comes from crude venoms rather than purified peptide components, making it difficult to attribute effects to specific peptides. The clinical relevance of the observed genotoxicity at therapeutic doses is largely unknown."},{"rthcId":"RPEP-07396","title":"Effects of SGLT2 inhibitors and GLP1-receptor agonists on cardiovascular and limb events in peripheral artery disease: A review.","authors":"Skeik, Nedaa; Elejla, Sewar A; Sethi, Anish; Manunga, Jesse; Mirza, Aleem","year":2023,"journal":"Vascular medicine (London, England), 28(1), 62-76","doi":"10.1177/1358863X221143811","pmid":"36593757","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Both SGLT2 inhibitors and GLP-1 receptor agonists have shown significant reductions in major adverse cardiovascular events (MACE) in type 2 diabetes patients with cardiovascular risk. However, patients with peripheral artery disease (PAD) have been consistently underrepresented in these trials. Notably, one major canagliflozin trial showed a signal of increased amputation risk, raising specific concerns for the PAD population.\n\nThe review found that while cardiovascular benefits appear to extend to PAD patients based on limited subgroup analyses, dedicated PAD-focused trial data for both drug classes remains scarce.","whyItMatters":"Peripheral artery disease affects millions of people with diabetes and carries high risks of amputation, heart attack, and death. GLP-1 receptor agonists represent one of the most promising drug classes for reducing cardiovascular events in diabetic patients, but their specific effects on limb outcomes in PAD are poorly understood. The amputation signal with canagliflozin has created uncertainty about SGLT2 inhibitor safety in this population, making GLP-1 RAs potentially more relevant for PAD patients.","specificNumbers":"2 drug classes reviewed (SGLT2i, GLP1-RA) · MACE reduction demonstrated · PAD patients underrepresented in trials · Amputation signal with canagliflozin flagged","methodology":"This was a narrative literature review summarizing published clinical trials, subgroup analyses, and societal guideline recommendations for SGLT2 inhibitors and GLP-1 receptor agonists in patients with cardiovascular disease, with a focus on data available for the peripheral artery disease subpopulation.","limitations":"As a narrative review, no systematic search or meta-analysis was conducted. The main limitation acknowledged by the authors is the lack of dedicated PAD-focused trials for either drug class — most conclusions about PAD patients are drawn from subgroup analyses of larger cardiovascular outcome trials, which may be underpowered. The amputation signal with canagliflozin has not been definitively linked to the drug mechanism."},{"rthcId":"RPEP-07397","title":"Growth Hormone Secretagogues as Potential Therapeutic Agents to Restore Growth Hormone Secretion in Older Subjects to Those Observed in Young Adults.","authors":"Smith, Roy G; Thorner, Michael O","year":2023,"journal":"The journals of gerontology. Series A, Biological sciences and medical sciences, 78(Suppl 1), 38-43","doi":"10.1093/gerona/glad022","pmid":"37325967","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07398","title":"Beta-defensins as marker for male fertility: a comprehensive review†.","authors":"Solanki, Subhash; Kumar, Vijay; Kashyap, Poonam; Kumar, Rakesh; De, Sachinandan; Datta, Tirtha Kumar","year":2023,"journal":"Biology of reproduction, 108(1), 52-71","doi":"10.1093/biolre/ioac197","pmid":"36322147","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07399","title":"Incretins and cardiovascular disease: to the heart of type 2 diabetes?","authors":"Solini, Anna; Tricò, Domenico; Del Prato, Stefano","year":2023,"journal":"Diabetologia, 66(10), 1820-1831","doi":"10.1007/s00125-023-05973-w","pmid":"37542009","tags":[],"studyType":"review","evidenceStrength":"high","keyFinding":"GLP-1 receptor agonists provide cardiovascular protection through multiple mechanisms: improved insulin secretion and action, weight loss, blood pressure lowering, improved lipid profiles, and direct beneficial effects on the heart and blood vessels. These are combined with anti-inflammatory and antioxidant properties that produce robust, consistent reductions in atherothrombotic events, particularly in type 2 diabetes patients with established cardiovascular disease.\n\nThe review also highlights that upcoming dual (GIP/GLP-1) and triple incretin receptor agonists may further expand cardiovascular protection possibilities. The evidence has led professional societies to formally recommend GLP-1 RAs for cardiovascular risk reduction in type 2 diabetes.","whyItMatters":"This review consolidates the evidence that GLP-1 drugs do far more than lower blood sugar — they directly protect the cardiovascular system through multiple independent pathways. This paradigm shift has transformed diabetes treatment from glucose-centric management to cardiovascular risk reduction as a primary goal.","specificNumbers":"Multiple cardiovascular outcome trials reviewed · Consistent MACE reductions · Benefits across GLP-1 RA structural classes · Guideline recommendations from major societies","methodology":"Narrative review summarizing cardiovascular outcome trial data, mechanistic studies, and real-world evidence for GLP-1 receptor agonist cardiovascular protection. Covers both glycaemic and non-glycaemic mechanisms and discusses emerging dual/triple agonists.","limitations":"As a narrative review, it synthesizes existing data without conducting new meta-analyses. Some mechanistic pathways are still being elucidated. The review was published before several key trials (e.g., SELECT, FLOW) reported full results."},{"rthcId":"RPEP-07400","title":"Bullous pemphigoid triggered by dulaglutide: a case report and a review of the literature.","authors":"Sonego, Benedetta; Zelin, Enrico; Zalaudek, Iris; di Meo, Nicola","year":2023,"journal":"Dermatology reports, 15(3), 9676","doi":"10.4081/dr.2023.9676","pmid":"37822982","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07401","title":"In vitro gastrointestinal digestion of buckwheat (Fagopyrum esculentum Moench) protein: release and structural characteristics of novel bioactive peptides stimulating gut cholecystokinin secretion.","authors":"Song, Hongdong; Wang, Qingyu; Shao, Zhuwei; Wang, Xinyue; Cao, Hongwei; Huang, Kai; Sun, Qiqi; Sun, Zhenliang; Guan, Xiao","year":2023,"journal":"Food & function, 14(16), 7469-7477","doi":"10.1039/d3fo01951a","pmid":"37489980","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07402","title":"Supramolecular assembly of a trivalent peptide hydrogel vaccine for cancer immunotherapy.","authors":"Song, Huijuan; Su, Qi; Nie, Yu; Zhang, Chuangnian; Huang, Pingsheng; Shi, Shengbin; Liu, Qiang; Wang, Weiwei","year":2023,"journal":"Acta biomaterialia, 158, 535-546","doi":"10.1016/j.actbio.2022.12.070","pmid":"36632876","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07403","title":"Improving ACE inhibitory activity of hazelnut peptide modified by plastein: Physicochemical properties and action mechanism.","authors":"Song, Wentian; Fu, Junxi; Zeng, Qi; Lu, Hongyan; Wang, Ji; Fang, Li; Liu, Xiaoting; Min, Weihong; Liu, Chunlei","year":2023,"journal":"Food chemistry, 402, 134498","doi":"10.1016/j.foodchem.2022.134498","pmid":"36303388","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07404","title":"Efficient recombinant production of mouse-derived cryptdin family peptides by a novel facilitation strategy for inclusion body formation.","authors":"Song, Yuchi; Wang, Yi; Yan, Shaonan; Nakamura, Kiminori; Kikukawa, Takashi; Ayabe, Tokiyoshi; Aizawa, Tomoyasu","year":2023,"journal":"Microbial cell factories, 22(1), 9","doi":"10.1186/s12934-023-02016-2","pmid":"36635697","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"By co-expressing cryptdins with human alpha-lactalbumin in the Origami B E. coli strain to promote inclusion body formation through erroneous intermolecular disulfide bonds, all six cryptdin isoforms were successfully produced, refolded, and purified. The key biological finding was that despite showing no significant structural differences by circular dichroism analysis, each Crp isoform exhibited completely different trends in antimicrobial activity against Gram-positive and Gram-negative bacteria. This functional divergence among structurally similar peptides was unexpected.","whyItMatters":"The cryptdin family is the mouse model for studying human alpha-defensins (HD-5 and HD-6), which are key components of gut innate immunity. The discovery that structurally similar defensins have dramatically different antimicrobial spectra challenges the assumption that defensin family members are functionally redundant. Understanding these differences could inform the design of defensin-based antibiotics and shed light on how the gut immune system uses a portfolio of similar but functionally distinct peptides.","specificNumbers":"","methodology":"Researchers developed a recombinant expression system in E. coli using co-expression with human alpha-lactalbumin to promote stable inclusion body formation. They used the Origami B strain to enhance production through erroneous intermolecular disulfide bonds. Peptides were refolded in vitro and purified by reversed-phase HPLC. Yields were further improved by deformylation. Structural analysis used circular dichroism, and antimicrobial activity was tested against panels of Gram-positive and Gram-negative bacteria.","limitations":"The peptides studied are mouse cryptdins, not human defensins, so the activity profiles may not directly translate. The antimicrobial testing was in vitro only — no gut infection models were used. The study could not explain the mechanistic basis for the activity differences, since structural analysis by circular dichroism didn't reveal significant conformational differences. More detailed structural methods (NMR, cryo-EM) may be needed to understand the functional divergence."},{"rthcId":"RPEP-07405","title":"Phospholipid Encapsulation of an Anti-Fibrotic Endopeptide to Enhance Cellular Uptake and Myocardial Retention.","authors":"Sonkawade, Swati D; Xu, Shirley; Kim, Minhyung; Nepali, Sarmila; Karambizi, Victoire-Grace; Sexton, Sandra; Turowski, Steven G; Li, Kunpeng; Spernyak, Joseph A; Lovell, Jonathan F; George, Anthony; Suwal, Sujit; Sharma, Umesh C; Pokharel, Saraswati","year":2023,"journal":"Cells, 12(12)","doi":"10.3390/cells12121589","pmid":"37371059","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07406","title":"Intranasal Oxytocin in Pediatric Populations: Exploring the Potential for Reducing Irritability and Modulating Neural Responses: A Mini Review.","authors":"Sorenson, Kennet; Kendall, Emilee; Grell, Hannah; Kang, Minjoo; Shaffer, Christopher; Hwang, Soonjo","year":2023,"journal":"Journal of psychiatry and brain science, 8(4)","doi":"10.20900/jpbs.20230008","pmid":"37990750","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 15 pediatric RCTs in autism spectrum disorder, Prader-Willi syndrome, and Phelan-McDermid syndrome, intranasal oxytocin showed neuroimaging evidence of modulating reward processing and social-emotional brain areas.\n\nHowever, clinical results were mixed, with changes in irritability mainly documented as adverse events rather than primary outcomes. The review identifies the lack of established pharmacodynamic and pharmacokinetic models for intranasal oxytocin as a key barrier, along with small sample sizes and inconsistent dosing across studies.","whyItMatters":"Irritability is one of the most common and disabling symptoms in children with neurodevelopmental disorders, yet treatment options are limited. If intranasal oxytocin can be shown to reliably reduce emotional overreactivity through its effects on brain circuits, it could fill a significant therapeutic gap — but only with better-designed trials using consistent dosing and appropriate outcome measures.","specificNumbers":"","methodology":"Mini-review of 15 randomized controlled trials of intranasal oxytocin in pediatric populations (children with ASD, Prader-Willi syndrome, or Phelan-McDermid syndrome). The review assessed both clinical outcomes and neuroimaging findings related to emotional processing and social behavior.","limitations":"Most of the 15 reviewed trials had small sample sizes. Dosing varied substantially across studies, making comparisons difficult. Changes in irritability were primarily captured as adverse events rather than pre-specified primary outcomes, limiting the strength of conclusions about efficacy. The pharmacokinetics of intranasal oxytocin in children remain poorly characterized."},{"rthcId":"RPEP-07407","title":"Bulevirtide in the Treatment of Hepatitis Delta: Drug Discovery, Clinical Development and Place in Therapy.","authors":"Soriano, Vicente; Moreno-Torres, Victor; Treviño, Ana; Corral, Octavio; de Mendoza, Carmen","year":2023,"journal":"Drug design, development and therapy, 17, 155-166","doi":"10.2147/DDDT.S379964","pmid":"36712949","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07408","title":"Thymosin beta 4: A potential novel adjunct treatment for bacterial keratitis.","authors":"Sosne, Gabriel; Berger, Elizabeth A","year":2023,"journal":"International immunopharmacology, 118, 109953","doi":"10.1016/j.intimp.2023.109953","pmid":"37018981","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07409","title":"The Health-promoting Potential of Edible Mushroom Proteins.","authors":"Sousa, Ana Sofia; Araújo-Rodrigues, Helena; Pintado, Manuela Estevez","year":2023,"journal":"Current pharmaceutical design, 29(11), 804-823","doi":"10.2174/1381612829666221223103756","pmid":"36567303","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07410","title":"GLP-1 receptor agonism and GIP receptor antagonism induce substantial alterations in enteroendocrine and islet cell populations in obese high fat fed mice.","authors":"Sridhar, Ananyaa; Khan, Dawood; Flatt, Peter R; Moffett, Charlotte R; Irwin, Nigel","year":2023,"journal":"Peptides, 169, 171093","doi":"10.1016/j.peptides.2023.171093","pmid":"37660881","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07411","title":"Designer GLP1 poly-agonist peptides in the management of diabesity.","authors":"Statham, Laura; Pelling, Melina; Hanson, Petra; Kyrou, Ioannis; Randeva, Harpal; Barber, Thomas M","year":2023,"journal":"Expert review of endocrinology & metabolism, 18(3), 231-240","doi":"10.1080/17446651.2023.2204976","pmid":"37089108","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07412","title":"Major adverse cardiovascular events among patients with type-2 diabetes, a nationwide cohort study comparing primary metabolic and bariatric surgery to GLP-1 receptor agonist treatment.","authors":"Stenberg, Erik; Näslund, Erik","year":2023,"journal":"International journal of obesity (2005), 47(4), 251-256","doi":"10.1038/s41366-023-01254-z","pmid":"36670155","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07413","title":"Adolescents with obesity treated with exenatide maintain endogenous GLP-1, reduce DPP-4, and improve glycemic control.","authors":"Stenlid, Rasmus; Cerenius, Sara Y; Wen, Quan; Aydin, Banu Küçükemre; Manell, Hannes; Chowdhury, Azazul; Kristinsson, Hjalti; Ciba, Iris; Gjessing, Erik S; Mörwald, Katharina; Gomahr, Julian; Heu, Verena; Weghuber, Daniel; Forslund, Anders; Bergsten, Peter","year":2023,"journal":"Frontiers in endocrinology, 14, 1293093","doi":"10.3389/fendo.2023.1293093","pmid":"38027106","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07414","title":"Screening for Inflammatory Markers Identifies IL-18Rα as a Potential Link between Exenatide and Its Anti-Inflammatory Effect: New Results from the Combat-JUDO Randomized Controlled Trial.","authors":"Stenlid, Rasmus; Cerenius, Sara Y; Manell, Hannes; Küçükemre Aydin, Banu; Mörwald, Katharina; Gomahr, Julian; Höghammar Mitkas, Marina; Eriksson, Ida; Ciba, Iris; Geiersberger, Sabine; Thivel, David; Weghuber, Daniel; Bergsten, Peter; Forslund, Anders","year":2023,"journal":"Annals of nutrition & metabolism, 79(6), 522-527","doi":"10.1159/000534725","pmid":"37883939","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07415","title":"Cell-permeable peptide-based delivery vehicles useful for subcellular targeting and beyond.","authors":"Stillger, Katharina; Neundorf, Ines","year":2023,"journal":"Cellular signalling, 109, 110796","doi":"10.1016/j.cellsig.2023.110796","pmid":"37423344","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07416","title":"Assessing adverse drug reaction reports for antidiabetic medications approved by the food and drug administration between 2012 and 2017: a pharmacovigilance study.","authors":"Stottlemyer, Britney A; McDermott, Michael C; Minogue, Mackenzie R; Gray, Matthew P; Boyce, Richard D; Kane-Gill, Sandra L","year":2023,"journal":"Therapeutic advances in drug safety, 14, 20420986231181334","doi":"10.1177/20420986231181334","pmid":"37332887","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07417","title":"Weight loss with subcutaneous semaglutide versus other glucagon-like peptide 1 receptor agonists in type 2 diabetes: a systematic review.","authors":"Stretton, Brandon; Kovoor, Joshua; Bacchi, Stephen; Chang, Shantel; Ngoi, Benjamin; Murray, Tess; Bristow, Thomas C; Heng, Jonathan; Gupta, Aashray; Ovenden, Christopher; Maddern, Guy; Thompson, Campbell H; Heilbronn, Leonie; Boyd, Mark; Rayner, Christopher; Talley, Nicholas J; Horowtiz, Michael","year":2023,"journal":"Internal medicine journal, 53(8), 1311-1320","doi":"10.1111/imj.16126","pmid":"37189293","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07418","title":"Ionizable polymeric nanocarriers for the codelivery of bi-adjuvant and neoantigens in combination tumor immunotherapy.","authors":"Su, Ting; Liu, Xiang; Lin, Shuibin; Cheng, Furong; Zhu, Guizhi","year":2023,"journal":"Bioactive materials, 26, 169-180","doi":"10.1016/j.bioactmat.2023.02.016","pmid":"36883121","tags":[],"studyType":"animal study","evidenceStrength":"low","keyFinding":"Researchers developed ionizable polymeric nanoparticles that co-deliver two immune-boosting agents (TLR7/8 and TLR9 agonists) alongside tumor-specific peptide neoantigens to lymph nodes, dramatically enhancing the immune response and tumor killing. These nanovaccines activated a broad range of antigen-presenting cells, generated robust anti-tumor T cell responses with immune memory, reduced tumor immunosuppression, and — critically — significantly enhanced the effectiveness of checkpoint immunotherapy (ICB) in mouse models of colorectal cancer and brain tumors (glioblastoma). This addresses a key limitation of current checkpoint drugs, which only work in a small subset of patients.","whyItMatters":"Immune checkpoint drugs (like anti-PD-1) have revolutionized cancer treatment but only help 20-30% of patients. The main reason: most patients lack enough pre-existing anti-tumor immune cells for the checkpoint drugs to unleash. Peptide neoantigen vaccines can create these immune cells, but current vaccines are limited by poor delivery to lymph nodes and weak immune stimulation. By co-packaging peptide neoantigens with dual immune boosters in pH-responsive nanoparticles, this study overcomes multiple bottlenecks simultaneously — potentially expanding checkpoint immunotherapy benefits to many more patients.","specificNumbers":"2 adjuvants (TLR7/8 + TLR9 agonists) · pH-responsive nanoparticles · Enhanced ICB in colorectal + GBM models · Robust T cell memory generated","methodology":"The researchers designed ionizable polymeric micellular nanoparticles that respond to pH changes (becoming active in the acidic environment of immune cell compartments). These nanoparticles co-delivered dual adjuvants (R848, a TLR7/8 agonist, and CpG, a TLR9 agonist) with peptide neoantigens specific to each tumor model. Efficacy was tested in murine colorectal cancer and orthotopic glioblastoma models, assessing T cell responses, immune memory, tumor immune microenvironment remodeling, and combination with immune checkpoint blockade therapy.","limitations":"This is a preclinical mouse study — human tumors have far more complex immune microenvironments and antigen landscapes. The neoantigen peptides used were selected for the specific mouse tumor models and may not represent the challenges of identifying neoantigens in diverse human cancers. Manufacturing scalability, stability, and safety of the nanoparticle platform in humans are unknown. Glioblastoma results are particularly preliminary given the blood-brain barrier challenges in human GBM."},{"rthcId":"RPEP-07419","title":"Lymph node-targeting adjuvant/neoantigen-codelivering vaccines for combination glioblastoma radioimmunotherapy.","authors":"Su, Ting; Zhou, Shurong; Yang, Suling; Humble, Nicholas; Zhang, Fuwu; Yu, Guocan; Bos, Paula D; Cheng, Furong; Valerie, Kristoffer; Zhu, Guizhi","year":2023,"journal":"Theranostics, 13(13), 4304-4315","doi":"10.7150/thno.84443","pmid":"37649594","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07420","title":"Affinity Purification and Molecular Characterization of Angiotensin-Converting Enzyme (ACE)-Inhibitory Peptides from Takifugu flavidus.","authors":"Su, Yongchang; Chen, Shicheng; Liu, Shuji; Wang, Yin; Chen, Xiaoting; Xu, Min; Cai, Shuilin; Pan, Nan; Qiao, Kun; Chen, Bei; Yang, Suping; Liu, Zhiyu","year":2023,"journal":"Marine drugs, 21(10)","doi":"10.3390/md21100522","pmid":"37888457","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07421","title":"Pharmacoeconomic analysis (CER) of Dulaglutide and Liraglutide in the treatment of patients with type 2 diabetes.","authors":"Su, Yu; Zhang, Shuo; Wu, Zezhen; Liu, Weiting; Chen, Jingxian; Deng, Feiying; Chen, Fengwu; Zhu, Dan; Hou, Kaijian","year":2023,"journal":"Frontiers in endocrinology, 14, 1054946","doi":"10.3389/fendo.2023.1054946","pmid":"36755915","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Both dulaglutide and liraglutide effectively reduced blood glucose, improved biochemical markers, and lowered insulin resistance (HOMA-IR) in women with type 2 diabetes over 24 weeks, with no significant difference in efficacy between the two drugs. However, dulaglutide was more cost-effective — lower overall treatment cost and fewer injection-related side effects — while maintaining equivalent cost-effectiveness ratios.","whyItMatters":"With GLP-1 drugs being expensive, understanding their comparative cost-effectiveness is crucial for healthcare systems and patients. This study provides real-world evidence that dulaglutide — a weekly injection — offers equivalent blood sugar control to liraglutide (a daily injection) at lower cost and with fewer side effects. The convenience of weekly dosing combined with lower cost and fewer complications makes a strong case for dulaglutide in resource-constrained settings.","specificNumbers":"n=96 women · 24-week treatment · 2 groups of 48 · blood glucose reduced in both (p<0.05) · no efficacy difference (p>0.05) · dulaglutide: lower cost (p<0.05) · dulaglutide: fewer side effects (p<0.05) · CER equivalent","methodology":"Randomized trial of 96 women with type 2 diabetes from June 2019 to December 2021. Patients were equally divided into liraglutide (control) and dulaglutide (observation) groups for 24 weeks. Outcomes included blood glucose levels, biochemical indices, HOMA-IR, cost-effectiveness ratio, and drug safety/side effect incidence.","limitations":"The study enrolled only women, so results may not generalize to men. The sample size of 96 is relatively small for a pharmacoeconomic study. Cost data may be specific to the Chinese healthcare system and not applicable globally. The 24-week follow-up may not capture long-term cost-effectiveness differences. Semaglutide (the most commonly prescribed GLP-1 RA) was not included in the comparison."},{"rthcId":"RPEP-07422","title":"Advances in transdermal siRNAs delivery: A review of current research progress.","authors":"Sufianov, Albert; Beilerli, Aferin; Kudriashov, Valentin; Ilyasova, Tatiana; Wenjie, Bu; Beylerli, Ozal","year":2023,"journal":"Non-coding RNA research, 8(3), 392-400","doi":"10.1016/j.ncrna.2023.05.008","pmid":"37275244","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07423","title":"Investigation of enhanced intracellular delivery of nanomaterials modified with novel cell-penetrating zwitterionic peptide-lipid derivatives.","authors":"Sugimoto, Yuri; Suga, Tadaharu; Umino, Mizuki; Yamayoshi, Asako; Mukai, Hidefumi; Kawakami, Shigeru","year":2023,"journal":"Drug delivery, 30(1), 2191891","doi":"10.1080/10717544.2023.2191891","pmid":"36964673","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07424","title":"A Comprehensive Review on Neuroendocrine Neoplasms: Presentation, Pathophysiology and Management.","authors":"Sultana, Qamar; Kar, Jill; Verma, Amogh; Sanghvi, Shreya; Kaka, Nirja; Patel, Neil; Sethi, Yashendra; Chopra, Hitesh; Kamal, Mohammad Amjad; Greig, Nigel H","year":2023,"journal":"Journal of clinical medicine, 12(15)","doi":"10.3390/jcm12155138","pmid":"37568540","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07425","title":"Formation of hierarchical assemblies by collagen peptides derived from fish skin and bladder and their subsequent application as antiperoxide agents in lipid-rich food.","authors":"Sumeet, Charitha; Bajaj, Mayur; Kumar, Indresh; Yelleti, Geethika; Asokan, Vishwadeep; Tagadghar, Pawan; Banerjee, Pradipta","year":2023,"journal":"Journal of biochemistry, 173(5), 353-373","doi":"10.1093/jb/mvac111","pmid":"36611219","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07426","title":"Immunotherapies targeting neoantigens are effective in PD-1 blockade-resistant tumors.","authors":"Sun, Changbo; Nagaoka, Koji; Kobayashi, Yukari; Maejima, Kazuhiro; Nakagawa, Hidewaki; Nakajima, Jun; Kakimi, Kazuhiro","year":2023,"journal":"International journal of cancer, 152(7), 1463-1475","doi":"10.1002/ijc.34382","pmid":"36451303","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07427","title":"Designed peptide amphiphiles as scaffolds for tissue engineering.","authors":"Sun, Weizhen; Gregory, David Alexander; Zhao, Xiubo","year":2023,"journal":"Advances in colloid and interface science, 314, 102866","doi":"10.1016/j.cis.2023.102866","pmid":"36898186","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies three main categories of peptide amphiphiles — amphiphilic peptides, lipidated peptide amphiphiles, and supramolecular peptide amphiphile conjugates — each with distinct design rules governing self-assembly into nanostructures (micelles, vesicles, ribbons, nanofibers). These structures closely resemble native extracellular matrix and have shown promise as tissue engineering scaffolds for bone, cartilage, and neural tissue regeneration in both in vitro and in vivo studies. The review also discusses 3D bio-fabrication strategies for creating PA hydrogels.","whyItMatters":"Tissue engineering holds enormous promise for treating injuries and degenerative diseases, but finding the right scaffold material has been a major challenge. Peptide amphiphiles offer a unique combination of precise molecular control, biological compatibility, and the ability to mimic natural tissue structures — potentially advancing regenerative medicine for some of the most difficult-to-treat conditions affecting bones, joints, and nerves.","specificNumbers":"","methodology":"This is a comprehensive narrative review covering the design principles of peptide amphiphiles, their self-assembly behavior, 3D bio-fabrication methods, and applications in tissue engineering. The authors synthesized published research on PA scaffolds for bone, cartilage, and neural tissue regeneration.","limitations":"As a review article, this paper synthesizes existing research rather than presenting new data. Many of the studies covered are preclinical (cell culture and animal models), with limited clinical translation to date. The challenges of scaling up PA production, achieving consistent quality, and navigating regulatory approval for clinical use are acknowledged but not resolved."},{"rthcId":"RPEP-07428","title":"Adverse event reporting of four anti-Calcitonin gene-related peptide monoclonal antibodies for migraine prevention: a real-world study based on the FDA adverse event reporting system.","authors":"Sun, Wenfang; Li, Yali; Xia, Binbin; Chen, Jing; Liu, Yang; Pang, Jingyao; Liu, Fang; Cheng, Hua","year":2023,"journal":"Frontiers in pharmacology, 14, 1257282","doi":"10.3389/fphar.2023.1257282","pmid":"38264523","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07429","title":"Comparative Efficacy and Safety of Five Anti-calcitonin Gene-related Peptide Agents for Migraine Prevention: A Network Meta-analysis.","authors":"Sun, Wenfang; Cheng, Hua; Xia, Binbin; Liu, Xianjun; Li, Yali; Wang, Xuemei; Liu, Chengjiang","year":2023,"journal":"The Clinical journal of pain, 39(10), 560-569","doi":"10.1097/AJP.0000000000001136","pmid":"37278480","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07430","title":"Structural insights into neurokinin 3 receptor activation by endogenous and analogue peptide agonists.","authors":"Sun, Wenjing; Yang, Fan; Zhang, Huanhuan; Yuan, Qingning; Ling, Shenglong; Wang, Yuanxia; Lv, Pei; Li, Zelin; Luo, Yifan; Liu, Dongsheng; Yin, Wanchao; Shi, Pan; Xu, H Eric; Tian, Changlin","year":2023,"journal":"Cell discovery, 9(1), 66","doi":"10.1038/s41421-023-00564-w","pmid":"37391393","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07431","title":"Cell-Penetrating Peptide-Based Delivery of Macromolecular Drugs: Development, Strategies, and Progress.","authors":"Sun, Zhe; Huang, Jinhai; Fishelson, Zvi; Wang, Chenhui; Zhang, Sihe","year":2023,"journal":"Biomedicines, 11(7)","doi":"10.3390/biomedicines11071971","pmid":"37509610","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"After 30+ years of research, cell-penetrating peptides (CPPs) remain one of the most versatile delivery vehicles for macromolecular drugs. The review identifies key optimization strategies: enhanced endosomal escape (overcoming intracellular trapping), extended blood circulation half-life, improved targeting efficiency through tissue-specific modifications, and stimuli-responsive designs that activate only under specific conditions (pH, enzymes, temperature). Clinical trials of CPP-based delivery systems have been conducted, and the review extracts the critical success factors from these trials.","whyItMatters":"Large molecule drugs (proteins, antibodies, nucleic acids) can't easily get into cells because they're too big to cross the cell membrane. CPPs solve this problem by essentially smuggling cargo across the membrane. This has applications across medicine: delivering gene therapies, getting anti-cancer drugs inside tumor cells, and enabling intracellular delivery of biological drugs that would otherwise be limited to extracellular targets. After decades of research, CPPs are finally maturing toward clinical use.","specificNumbers":"30+ years of CPP research · Multiple delivery strategies reviewed · Clinical trials documented · Macromolecular drug delivery (proteins, nucleic acids, etc.)","methodology":"Comprehensive review article covering CPP development history, classification, cellular uptake mechanisms, biological barriers, optimization strategies, and clinical trial progress for CPP-based macromolecular drug delivery systems.","limitations":"This is a review article, not an experimental study. While CPPs show excellent performance in lab settings, in vivo delivery efficiency remains lower due to biological barriers (serum stability, endosomal trapping, off-target distribution). Few CPP-based drugs have achieved clinical approval despite decades of research, suggesting translation challenges that the review acknowledges."},{"rthcId":"RPEP-07432","title":"MetaPep: A core peptide database for faster human gut metaproteomics database searches.","authors":"Sun, Zhongzhi; Ning, Zhibin; Cheng, Kai; Duan, Haonan; Wu, Qing; Mayne, Janice; Figeys, Daniel","year":2023,"journal":"Computational and structural biotechnology journal, 21, 4228-4237","doi":"10.1016/j.csbj.2023.08.025","pmid":"37692080","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07433","title":"Intraduodenal nutrient infusion differentially alters intestinal nutrient sensing, appetite, and satiety responses in lean and obese subjects.","authors":"Sundaresan, Sinju; Johnson, Connor; Dixon, Kala B; Dole, Michael; Kilkelly, Donna; Antoun, Joseph; Flynn, Charles Robb; Abumrad, Naji N; Tamboli, Robyn","year":2023,"journal":"The American journal of clinical nutrition, 118(3), 646-656","doi":"10.1016/j.ajcnut.2023.06.011","pmid":"37661107","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07434","title":"Empagliflozin and dulaglutide: community awareness project promotes improved access to newly funded medications for Pacific patients with type 2 diabetes.","authors":"Sundborn, Gerhard; Lesa, Fale; King, Graham; Vennell, Kate; Kozak, Henry; Pickering, Karen; Baker, John","year":2023,"journal":"The New Zealand medical journal, 136(1572), 66-74","doi":"10.26635/6965.5869","pmid":"36958323","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07435","title":"Acute postprandial gut hormone, leptin, glucose and insulin responses to resistant starch in obese children: a single blind crossover study.","authors":"Suntharesan, Jananie; Atapattu, Navoda; Jasinghe, Eresha; Ekanayake, Sagarika; de Silva, Delpachitra Acharige Gajabahu Harendra; Dunseath, Gareth; Luzio, Steohan; Premawardhana, Lakdasa","year":2023,"journal":"Archives of disease in childhood, 108(1), 47-52","doi":"10.1136/archdischild-2022-324203","pmid":"36347569","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The resistant starch meal (rice cooked with coconut oil, M2) produced significantly lower postprandial glucose (p<0.01 for multiple measures) and insulin values (p<0.05) compared to plain rice (M1) in obese children. Postprandial ghrelin — the 'hunger hormone' peptide — was significantly higher after plain rice compared to the coconut oil + lentils meal (M3, p<0.05), suggesting greater appetite suppression with the combined meal.\n\nHowever, the gut peptide hormones GLP-1 and PYY showed no significant differences between the three meals, and median satiety scores were also not significantly affected, indicating that the metabolic benefits occurred independently of these appetite-regulating peptides.","whyItMatters":"Childhood obesity is a growing global crisis, and simple dietary modifications that improve metabolic health are highly valuable. This is the first study to examine resistant starch effects on gut peptide hormones and glucose metabolism in children. The finding that simply cooking rice with coconut oil can significantly improve blood sugar responses in obese children offers a practical, low-cost dietary strategy that could be particularly impactful in rice-consuming populations worldwide.","specificNumbers":"","methodology":"This was a single-blind, non-randomized crossover study in 20 obese children aged 10-14 years without comorbidities. Three test meals were given in sequence after a 12-hour fast: plain rice (M1), rice cooked with coconut oil (M2), and rice cooked in coconut oil with lentils (M3). Blood samples were collected at multiple timepoints between 0-180 minutes and analyzed for glucose, insulin, leptin, GLP-1, ghrelin, and peptide YY (PYY).","limitations":"The study was non-randomized and single-blind with a small sample size of 20 children. Meals were given in a fixed sequence rather than randomized order, which could introduce order effects. The study only measured acute (3-hour) responses to a single meal, so long-term metabolic effects are unknown. Satiety scores showed no significant differences despite hormonal changes. The study population was limited to obese children without comorbidities from a single center."},{"rthcId":"RPEP-07436","title":"Tachykinin Receptor-Selectivity of the Potential Glioblastoma-Targeted Therapy, DOTA-[Thi8,Met(O2)11]-Substance P.","authors":"Suthiram, Janine; Pieters, Ané; Mohamed Moosa, Zulfiah; Zeevaart, Jan Rijn; Sathekge, Mike M; Ebenhan, Thomas; Anderson, Ross C; Newton, Claire L","year":2023,"journal":"International journal of molecular sciences, 24(3)","doi":"10.3390/ijms24032134","pmid":"36768456","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07437","title":"Effectiveness of three calcitonin gene-related peptide monoclonal antibodies for migraine: A 12-month, single-center, observational real-world study in Japan.","authors":"Suzuki, Keisuke; Suzuki, Shiho; Shiina, Tomohiko; Tatsumoto, Muneto; Fujita, Hiroaki; Haruyama, Yasuo; Hirata, Koichi","year":2023,"journal":"Cephalalgia : an international journal of headache, 43(5), 3331024231177649","doi":"10.1177/03331024231177649","pmid":"37231663","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07438","title":"Targeting the central melanocortin system for the treatment of metabolic disorders.","authors":"Sweeney, Patrick; Gimenez, Luis E; Hernandez, Ciria C; Cone, Roger D","year":2023,"journal":"Nature reviews. Endocrinology, 19(9), 507-519","doi":"10.1038/s41574-023-00855-y","pmid":"37365323","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07439","title":"Do GLP-1 Analogs Have a Place in the Treatment of PCOS? New Insights and Promising Therapies.","authors":"Szczesnowicz, Aleksandra; Szeliga, Anna; Niwczyk, Olga; Bala, Gregory; Meczekalski, Blazej","year":2023,"journal":"Journal of clinical medicine, 12(18)","doi":"10.3390/jcm12185915","pmid":"37762856","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07440","title":"Chronic Migraine as a Primary Chronic Pain Syndrome and Recommended Prophylactic Therapeutic Options: A Literature Review.","authors":"Szok, Délia; Csáti, Anett; Vécsei, László; Tajti, János","year":2023,"journal":"Life (Basel, Switzerland), 13(3)","doi":"10.3390/life13030665","pmid":"36983822","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07441","title":"Involvement of the Opioid Peptide Family in Cancer Progression.","authors":"Sánchez, Manuel Lisardo; Rodríguez, Francisco D; Coveñas, Rafael","year":2023,"journal":"Biomedicines, 11(7)","doi":"10.3390/biomedicines11071993","pmid":"37509632","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07442","title":"An integrated view of anti-inflammatory and antifibrotic targets for the treatment of NASH.","authors":"Tacke, Frank; Puengel, Tobias; Loomba, Rohit; Friedman, Scott L","year":2023,"journal":"Journal of hepatology, 79(2), 552-566","doi":"10.1016/j.jhep.2023.03.038","pmid":"37061196","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07443","title":"Impact of Peptide Structure on Colonic Stability and Tissue Permeability.","authors":"Taherali, Farhan; Chouhan, Nerisha; Wang, Fanjin; Lavielle, Sebastien; Baran, Maryana; McCoubrey, Laura E; Basit, Abdul W; Yadav, Vipul","year":2023,"journal":"Pharmaceutics, 15(7)","doi":"10.3390/pharmaceutics15071956","pmid":"37514143","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 11 oxytocin-based peptide modifications tested:\n- Native oxytocin's disulfide bond cyclization provided improved stability in a human colon model compared to a linear derivative\n- Chloroacetyl cyclization increased stability at 1.5h by 30.0%\n- Three D-amino acid substitutions (at Tyr, Ile, Leu) improved stability by 58.2% in linear and 79.1% in cyclic structures\n- Thioether and N-terminal acetylated cyclizations offered no additional protection\n- Three D-AA substitutions in cyclic oxytocin significantly increased permeability across rat colonic tissue, likely by favorably altering secondary structure\n- The site and number of D-AA substitutions were critical for stability","whyItMatters":"Nearly all peptide drugs require injection because they can't survive digestion. For conditions like inflammatory bowel disease and colorectal cancer, oral delivery that targets the colon would be ideal — getting the drug directly where it's needed. This study provides a blueprint for designing peptides that can withstand the colonic environment and cross intestinal tissue, potentially enabling oral peptide therapies for gut diseases.","specificNumbers":"","methodology":"Researchers synthesized native oxytocin and 11 structural analogs with various cyclization modifications (disulfide, chloroacetyl, thioether, N-terminal acetylated) and D-amino acid substitutions. Stability was tested in a human colon model measuring enzymatic degradation. Tissue permeability was assessed using ex vivo rat colonic tissue. Structural changes were analyzed to understand how modifications affected peptide properties.","limitations":"Oxytocin was used as a model peptide, and results may not directly translate to other therapeutic peptides with different structures and properties. Colonic stability was measured in an ex vivo model, not in vivo with full physiological conditions. Tissue permeability was assessed in rat colon, which may differ from human colon. The modifications that improved stability and permeability may alter the peptide's biological activity, which was not assessed. Formulation strategies for colon-targeted oral delivery were not included."},{"rthcId":"RPEP-07444","title":"Improvement of glycaemic control and treatment satisfaction by switching from liraglutide or dulaglutide to subcutaneous semaglutide in patients with type 2 diabetes: A multicentre, prospective, randomized, open-label, parallel-group comparison study (SWITCH-SEMA 1 study).","authors":"Takahashi, Yuka; Nomoto, Hiroshi; Yokoyama, Hiroki; Takano, Yoshinari; Nagai, So; Tsuzuki, Atsushi; Cho, Kyu Yong; Miya, Aika; Kameda, Hiraku; Takeuchi, Jun; Taneda, Shinji; Kurihara, Yoshio; Atsumi, Tatsuya; Nakamura, Akinobu; Miyoshi, Hideaki","year":2023,"journal":"Diabetes, obesity & metabolism, 25(6), 1503-1511","doi":"10.1111/dom.14998","pmid":"36722623","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07445","title":"In vivo direct cell-penetrating peptide mediated protein transduction system in Acyrthosiphon pisum.","authors":"Takenaka, Aya; Konno, Harutomo; Kikuta, Shingo","year":2023,"journal":"BMC research notes, 16(1), 231","doi":"10.1186/s13104-023-06514-9","pmid":"37749584","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07446","title":"PGNneo: A Proteogenomics-Based Neoantigen Prediction Pipeline in Noncoding Regions.","authors":"Tan, Xiaoxiu; Xu, Linfeng; Jian, Xingxing; Ouyang, Jian; Hu, Bo; Yang, Xinrong; Wang, Tao; Xie, Lu","year":2023,"journal":"Cells, 12(5)","doi":"10.3390/cells12050782","pmid":"36899918","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07447","title":"Development of Orally Bioavailable Peptides Targeting an Intracellular Protein: From a Hit to a Clinical KRAS Inhibitor.","authors":"Tanada, Mikimasa; Tamiya, Minoru; Matsuo, Atsushi; Chiyoda, Aya; Takano, Koji; Ito, Toshiya; Irie, Machiko; Kotake, Tomoya; Takeyama, Ryuuichi; Kawada, Hatsuo; Hayashi, Ryuji; Ishikawa, Shiho; Nomura, Kenichi; Furuichi, Noriyuki; Morita, Yuya; Kage, Mirai; Hashimoto, Satoshi; Nii, Keiji; Sase, Hitoshi; Ohara, Kazuhiro; Ohta, Atsushi; Kuramoto, Shino; Nishimura, Yoshikazu; Iikura, Hitoshi; Shiraishi, Takuya","year":2023,"journal":"Journal of the American Chemical Society, 145(30), 16610-16620","doi":"10.1021/jacs.3c03886","pmid":"37463267","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07448","title":"Hydrophobic modification improves the delivery of cell-penetrating peptides to eliminate intracellular pathogens in animals.","authors":"Tang, Qi; Tan, Peng; Dai, Zhaolai; Wang, Tao; Xu, Shenrui; Ding, Yakun; Jin, Junqi; Zhang, Xin; Zhang, Yucheng; Zhou, Chenlong; Yue, Zitian; Fu, Huiyang; Yan, Junshu; Ma, Xi","year":2023,"journal":"Acta biomaterialia, 157, 210-224","doi":"10.1016/j.actbio.2022.11.055","pmid":"36503077","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07449","title":"Thymosin α1 and Its Role in Viral Infectious Diseases: The Mechanism and Clinical Application.","authors":"Tao, Nana; Xu, Xie; Ying, Yuyuan; Hu, Shiyu; Sun, Qingru; Lv, Guiyuan; Gao, Jianli","year":2023,"journal":"Molecules (Basel, Switzerland), 28(8)","doi":"10.3390/molecules28083539","pmid":"37110771","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Thymosin alpha-1 exerts its immunostimulatory effects by interacting with multiple Toll-like receptors (TLRs) on immune cells. It binds to TLR3, TLR4, and TLR9, activating downstream IRF3 and NF-κB signaling pathways, which promote the proliferation and activation of immune cells. Additionally, Tα1 activates TLR2/NF-κB, TLR2/p38MAPK, and TLR7/MyD88 pathways, stimulating cytokine production that enhances both innate and adaptive immune responses.\n\nThis multi-pathway activation explains why Tα1 is effective across different viral infections — it broadly strengthens immune surveillance and response rather than targeting a single mechanism.","whyItMatters":"Thymosin alpha-1 is one of the most established therapeutic peptides in clinical use, particularly in Asia where it is widely prescribed for viral hepatitis. This review provides a comprehensive molecular explanation for why it works, connecting specific receptor interactions to clinical outcomes. Understanding these mechanisms could guide the development of improved immunomodulatory peptides and help identify which patients are most likely to benefit.","specificNumbers":"","methodology":"This is a systematic review that synthesizes published research on thymosin alpha-1, including its biochemical characteristics, immunomodulatory properties, molecular mechanisms of action, and clinical applications in antiviral therapy. The authors analyzed both pharmacological research and clinical data from its use in hepatitis B, hepatitis C, and AIDS.","limitations":"As a review article, this paper synthesizes existing research rather than presenting new clinical data. The authors note that while there are many reports on Tα1's clinical use, there has been no systematic review analyzing its exact clinical efficacy through immune modulation — which this review attempts to address but is limited by the quality and heterogeneity of the underlying studies. Most clinical experience comes from hepatitis patients in Asian populations, and applicability to other contexts needs more investigation."},{"rthcId":"RPEP-07450","title":"Mechanisms and possible hepatoprotective effects of glucagon-like peptide-1 receptor agonists and other incretin receptor agonists in non-alcoholic fatty liver disease.","authors":"Targher, Giovanni; Mantovani, Alessandro; Byrne, Christopher D","year":2023,"journal":"The lancet. Gastroenterology & hepatology, 8(2), 179-191","doi":"10.1016/S2468-1253(22)00338-7","pmid":"36620987","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07451","title":"Proteolysis-Targeting Chimera (PROTAC) Delivery into the Brain across the Blood-Brain Barrier.","authors":"Tashima, Toshihiko","year":2023,"journal":"Antibodies (Basel, Switzerland), 12(3)","doi":"10.3390/antib12030043","pmid":"37489365","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07452","title":"Identification of T Cell Receptors Targeting a Neoantigen Derived from Recurrently Mutated FGFR3.","authors":"Tate, Tomohiro; Matsumoto, Saki; Nemoto, Kensaku; Leisegang, Matthias; Nagayama, Satoshi; Obama, Kazutaka; Nakamura, Yusuke; Kiyotani, Kazuma","year":2023,"journal":"Cancers, 15(4)","doi":"10.3390/cancers15041031","pmid":"36831375","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07453","title":"Dulaglutide as a demethylating agent to improve the outcome of breast cancer.","authors":"Tatsch, Júlia M; Furman, Diana P; Nobre, Rodrigo Mb; Wurzer, Karin M; da Silva, Liziane Cm; Picheth, Guilherme F; Ramos, Edneia As; Acco, Alexandra; Klassen, Giseli","year":2023,"journal":"Epigenomics, 15(24), 1309-1322","doi":"10.2217/epi-2023-0332","pmid":"38174426","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07454","title":"Lacripep for the Treatment of Primary Sjögren-Associated Ocular Surface Disease: Results of the First-In-Human Study.","authors":"Tauber, Joseph; Laurie, Gordon W; Parsons, Edward C; Odrich, Marc G","year":2023,"journal":"Cornea, 42(7), 847-857","doi":"10.1097/ICO.0000000000003091","pmid":"35942530","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07455","title":"Recent Advances in In Vitro and In Vivo Studies of Antioxidant, ACE-Inhibitory and Anti-Inflammatory Peptides from Legume Protein Hydrolysates.","authors":"Tawalbeh, Deia; Al-U'datt, Muhammad H; Wan Ahmad, Wan Amir Nizam; Ahmad, Fisal; Sarbon, Norizah Mhd","year":2023,"journal":"Molecules (Basel, Switzerland), 28(6)","doi":"10.3390/molecules28062423","pmid":"36985395","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07456","title":"The impact of COVID-19 on BNP, NT-proBNP and ANP in heart failure.","authors":"Tawfeeq, Rawaz D; Alwan, Mohammed H; Ismael, Ava T; Hamad, Badraldin K","year":2023,"journal":"Cellular and molecular biology (Noisy-le-Grand, France), 69(9), 143-148","doi":"10.14715/cmb/2023.69.9.21","pmid":"37807321","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07457","title":"Alternate-day fat diet and exenatide modulate the brain leptin JAK2/STAT3/SOCS3 pathway in a fat diet-induced obesity and insulin resistance mouse model.","authors":"Tawfik, Mona K; Badran, Dahlia I; Keshawy, Mohammed M; Makary, Samy; Abdo, Mohamed","year":2023,"journal":"Archives of medical science : AMS, 19(5), 1508-1519","doi":"10.5114/aoms/158534","pmid":"37732053","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07458","title":"Use and Interchange of Incretin Mimetics in the Treatment of Metabolic Diseases: A Narrative Review.","authors":"Teague, Madison; Martinez, Amanda; Walker, Erica; El-Rifai, Mohammad; Carris, Nicholas W","year":2023,"journal":"Clinical therapeutics, 45(3), 248-261","doi":"10.1016/j.clinthera.2023.02.003","pmid":"36872170","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07459","title":"Liraglutide 3.0 mg and mental health: can psychiatric symptoms be associated to adherence to therapy? Insights from a clinical audit.","authors":"Tempia Valenta, Silvia; Stecchi, Michele; Perazza, Federica; Nuccitelli, Chiara; Villanova, Nicola; Pironi, Loris; Atti, Anna Rita; Petroni, Maria Letizia","year":2023,"journal":"Eating and weight disorders : EWD, 28(1), 99","doi":"10.1007/s40519-023-01625-5","pmid":"38015342","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07460","title":"A case of frequent hypoglycemic attacks successfully controlled with capecitabine plus temozolomide and 177Lu-DOTATATE peptide receptor radionuclide therapy in a patient with recurrent pancreatic insulinoma.","authors":"Terashima, Takeshi; Yamashita, Tatsuya; Takemura, Naoki; Inaki, Anri; Shimizu, Akinori; Harada, Kenichi; Yamashita, Taro; Kinuya, Seigo; Hanada, Keiji","year":2023,"journal":"Clinical journal of gastroenterology, 16(5), 767-771","doi":"10.1007/s12328-023-01824-8","pmid":"37405635","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The combination of capecitabine plus temozolomide (CAPTEM) and 177Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) achieved both symptom control and tumor shrinkage in a patient with heavily pretreated metastatic insulinoma. The patient had previously failed sunitinib, everolimus, lanreotide, and streptozocin plus 5-fluorouracil.\n\nAfter starting the combined regimen, the frequency of hypoglycemic attacks decreased sufficiently to eliminate the need for daily intravenous glucose infusions, allowing hospital discharge on day 58. CT imaging at 8 months confirmed ongoing shrinkage of both the primary pancreatic tumor and metastatic lesions, with no major adverse events reported.","whyItMatters":"Insulinomas that recur after surgery and resist multiple drug therapies represent a serious clinical challenge, as the uncontrolled insulin secretion can cause life-threatening hypoglycemia. 177Lu-DOTATATE (marketed as Lutathera) is a peptide-based therapy that uses a somatostatin analog to target and deliver radiation directly to neuroendocrine tumor cells. This case demonstrates that even when many standard options have failed, combining PRRT with chemotherapy may offer meaningful disease control — highlighting the growing role of peptide-targeted therapies in hard-to-treat cancers.","specificNumbers":"","methodology":"This is a single-patient case report. The patient received CAPTEM chemotherapy followed by 177Lu-DOTATATE PRRT. Treatment response was monitored through clinical assessment of hypoglycemic attack frequency, need for glucose infusions, and CT imaging to evaluate tumor size changes over an 8-month follow-up period.","limitations":"As a single case report, the findings cannot be generalized — what worked for this one patient may not work for others with insulinoma. There was no control group or comparison arm. The 8-month follow-up is relatively short for assessing long-term cancer outcomes. It is unclear whether the benefit came primarily from CAPTEM, PRRT, or specifically their combination. The somatostatin receptor status of the tumor was not detailed in the abstract."},{"rthcId":"RPEP-07461","title":"Comparative Study of the Efficacy of Anti-CGRP mAbs on Migraineurs: Analysis of the First Year of Therapy, 1-Month Suspension Period, and Reprisal.","authors":"Tereshko, Yan; Dal Bello, Simone; Pez, Sara; Belgrado, Enrico; Lettieri, Christian; Ercole, Bruno Hector; Cellante, Giulia; Del Regno, Caterina; Sportelli, Giuseppe; Ermanis, Giovanni; Versace, Salvatore; Merlino, Giovanni; Gigli, Gian Luigi; Valente, Mariarosaria","year":2023,"journal":"Journal of clinical medicine, 12(23)","doi":"10.3390/jcm12237329","pmid":"38068383","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07462","title":"Cancer therapy with iRGD as a tumor-penetrating peptide.","authors":"Thirumalai, Anbazhagan; Girigoswami, Koyeli; Pallavi, Pragya; Harini, Karthick; Gowtham, Pemula; Girigoswami, Agnishwar","year":2023,"journal":"Bulletin du cancer, 110(12), 1288-1300","doi":"10.1016/j.bulcan.2023.08.009","pmid":"37813754","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07463","title":"Enrofloxacin exposure induces anxiety-like behavioral responses in zebrafish by affecting the microbiota-gut-brain axis.","authors":"Tian, Dandan; Shi, Wei; Yu, Yihan; Zhou, Weishang; Tang, Yu; Zhang, Weixia; Huang, Lin; Han, Yu; Liu, Guangxu","year":2023,"journal":"The Science of the total environment, 858(Pt 3), 160094","doi":"10.1016/j.scitotenv.2022.160094","pmid":"36372168","tags":[],"studyType":"animal","evidenceStrength":"early","keyFinding":"Zebrafish exposed to the antibiotic enrofloxacin at environmentally realistic levels (60 μg/L for 28 days) developed anxiety-like behaviors in two standard behavioral tests. The antibiotic disrupted the gut microbiome by increasing Bacteroidetes and lowering the Firmicutes/Bacteroidetes ratio, while significantly altering multiple peptide signaling molecules: intestinal GLP-1, 5-HT, IL-6, and TNF-α were elevated, plasma ACTH and cortisol were reduced, and brain levels of CRH, BDNF, and neuropeptide Y were increased — suggesting the microbiota-gut-brain axis mediated the behavioral changes.","whyItMatters":"This study shows how environmental antibiotic contamination can disrupt gut bacteria in ways that alter peptide hormone signaling throughout the body and brain, ultimately changing behavior. It highlights the interconnectedness of the microbiome, gut peptides like GLP-1, and brain neuropeptides like NPY in regulating mood and anxiety.","specificNumbers":"60 μg/L enrofloxacin · 28-day exposure · Elevated GLP-1, 5-HT, IL-6, TNF-α in gut · Reduced ACTH and cortisol in plasma · Elevated CRH, BDNF, NPY in brain","methodology":"Zebrafish were exposed to enrofloxacin at 6 and 60 μg/L for 28 days. Anxiety-like behavior was measured using light-dark test and novel tank task. Gut microbiome composition was analyzed. Intestinal, plasma, and brain levels of multiple peptides and signaling molecules were measured.","limitations":"Zebrafish study — results may not directly translate to humans. The antibiotic used (enrofloxacin) is primarily veterinary. Correlation between microbiome changes and peptide alterations does not prove causation. Sample size not specified in abstract. No germ-free controls to confirm microbiome-mediated mechanism."},{"rthcId":"RPEP-07464","title":"Association of serum thymosin β4 with malnutrition-inflammation-atherosclerosis syndrome in peritoneal dialysis patients: a cross-sectional study.","authors":"Tian, Jiakun; Zhang, Rong; Zhu, Nan; Gu, Lijie; Guo, Yunshan; Yuan, Weijie","year":2023,"journal":"Renal failure, 45(1), 2202761","doi":"10.1080/0886022X.2023.2202761","pmid":"37133832","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07465","title":"Elevated Ghrelin Promotes Hippocampal Ghrelin Receptor Defects in Humanized Amyloid-β Knockin Mice During Aging.","authors":"Tian, Jing; Du, Eric; Jia, Kun; Wang, Tienju; Guo, Lan; Zigman, Jeffrey M; Du, Heng","year":2023,"journal":"Journal of Alzheimer's disease : JAD, 96(4), 1579-1592","doi":"10.3233/JAD-231002","pmid":"38007666","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The study found that humanized amyloid-beta knockin mice develop concurrent plasma ghrelin elevation and hippocampal ghrelin receptor (GHSR) desensitization as disease progresses. Crucially, the researchers demonstrated that the ghrelin elevation is not a compensatory response to receptor dysfunction. Instead, chronic overstimulation by elevated ghrelin drives enhanced receptor internalization, causing the receptors to become desensitized. This creates a vicious cycle: rising ghrelin leads to receptor shutdown, resulting in hippocampal ghrelin resistance and synaptic injury.","whyItMatters":"Ghrelin-based therapies have been proposed as potential Alzheimer's treatments because ghrelin supports memory and synaptic function. However, this study reveals that in Alzheimer's-like conditions, the ghrelin system itself becomes dysfunctional — elevated ghrelin actually worsens the problem by shutting down its own receptors. This fundamentally changes how researchers should think about ghrelin-targeted interventions for Alzheimer's disease.","specificNumbers":"","methodology":"Researchers used humanized amyloid-beta knockin (hAβ KI) mice — a model of late-onset Alzheimer's disease — and measured plasma ghrelin levels alongside hippocampal GHSR function over time. They combined in vivo mouse studies with in vitro primary neuron cultures to dissect the mechanism. Multidisciplinary techniques were used to assess receptor desensitization, internalization, and the functional consequences of chronic ghrelin overstimulation.","limitations":"This study was conducted in a mouse model and primary neuron cultures, so the findings may not directly translate to human Alzheimer's disease. The hAβ KI model represents one aspect of AD pathology (amyloid-beta) and may not capture the full complexity of the human disease. Specific quantitative data on ghrelin levels and receptor changes were not detailed in the abstract, making it difficult to assess effect sizes."},{"rthcId":"RPEP-07466","title":"Stable Isotope Labeling-Based Nontargeted Strategy for Characterization of the In Vitro Metabolic Profile of a Novel Doping BPC-157 in Doping Control by UHPLC-HRMS.","authors":"Tian, Tian; Jing, Jing; Li, Yuanyuan; Wang, Yang; Deng, Xiaojun; Shan, Yuanhong","year":2023,"journal":"Molecules (Basel, Switzerland), 28(21)","doi":"10.3390/molecules28217345","pmid":"37959764","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Using 13C/15N-labeled BPC-157 combined with UHPLC-HRMS, the researchers constructed a workflow for automatic isotope pair picking and identified nine metabolites from two incubation models. Eight metabolites were produced through conventional amide-bond breaking, while one was generated by a novel metabolic pathway not previously described for BPC-157.\n\nA validated detection method for BPC-157 and its five main metabolites in human urine achieved detection limits of 0.01–0.11 ng/mL, with excellent linearity across a range of 0.02–50 ng/mL (R² > 0.999) and recovery rates above 90%. This provides improved targets for anti-doping control.","whyItMatters":"BPC-157 is increasingly being used as a doping agent in sports, but detecting it has been challenging because its metabolic pathways were poorly understood. This study provides the first comprehensive metabolic profile using isotope labeling, giving anti-doping authorities better detection targets. It also reveals new information about how BPC-157 is processed in the body.","specificNumbers":"","methodology":"The researchers used stable isotope labeling with 13C/15N-labeled BPC-157 combined with ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS). They incubated BPC-157 in two in vitro models, used automatic isotope pair picking to identify metabolites, and then developed and validated a urine detection method for BPC-157 and its metabolites.","limitations":"The metabolic profiling was conducted in vitro, meaning the results may not fully reflect how BPC-157 is metabolized in a living human body. In vivo metabolism involves additional factors like gut bacteria, liver processing, and tissue distribution that weren't captured. The study focused on urine detection and did not address blood or other matrices."},{"rthcId":"RPEP-07467","title":"Exploring the Chemical Properties and Medicinal Applications of Tetramethylthiocycloheptyne Sulfoximine Used in Strain-Promoted Azide-Alkyne Cycloaddition Reactions.","authors":"Timmers, Matt; Kipper, Andi; Frey, Raphael; Notermans, Stef; Voievudskyi, Maksym; Wilson, Claire; Hentzen, Nina; Ringle, Michael; Bovino, Clara; Stump, Bernhard; Rijcken, Cristianne J F; Vermonden, Tina; Dijkgraaf, Ingrid; Liskamp, Rob","year":2023,"journal":"Pharmaceuticals (Basel, Switzerland), 16(8)","doi":"10.3390/ph16081155","pmid":"37631074","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07468","title":"Cell-Penetrating Peptides as Vehicles for Delivery of Therapeutic Nucleic Acids. Mechanisms and Application in Medicine.","authors":"Timotievich, Ekaterina D; Shilovskiy, Igor P; Khaitov, Musa R","year":2023,"journal":"Biochemistry. Biokhimiia, 88(11), 1800-1817","doi":"10.1134/S0006297923110111","pmid":"38105200","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07469","title":"Mucosal absorption of antibody drugs enhanced by cell-penetrating peptides anchored to a platform of polysaccharides.","authors":"Tomono, Takumi; Yagi, Haruya; Igi, Ryoji; Tabaru, Akihiro; Fujimoto, Koichi; Enomoto, Kaho; Ukawa, Masami; Miyata, Kohei; Shigeno, Koichi; Sakuma, Shinji","year":2023,"journal":"International journal of pharmaceutics, 647, 123499","doi":"10.1016/j.ijpharm.2023.123499","pmid":"37832700","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07470","title":"Eptifibatide, an Older Therapeutic Peptide with New Indications: From Clinical Pharmacology to Everyday Clinical Practice.","authors":"Tonin, Gašper; Klen, Jasna","year":2023,"journal":"International journal of molecular sciences, 24(6)","doi":"10.3390/ijms24065446","pmid":"36982519","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07471","title":"Mycobacterium abscessus Opsonization Allows an Escape from the Defensin Bactericidal Action in Drosophila.","authors":"Touré, Hamadoun; Durand, Nicolas; Guénal, Isabelle; Herrmann, Jean-Louis; Girard-Misguich, Fabienne; Szuplewski, Sébastien","year":2023,"journal":"Microbiology spectrum, 11(4), e0077723","doi":"10.1128/spectrum.00777-23","pmid":"37260399","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07472","title":"In Vivo Mechanism of Action of Sodium Caprate for Improving the Intestinal Absorption of a GLP1/GIP Coagonist Peptide.","authors":"Tran, Huyen; Aihara, Eitaro; Mohammed, Faiz Ahmad; Qu, Hongchang; Riley, Andrew; Su, Yuan; Lai, Xianyin; Huang, Siyuan; Aburub, Aktham; Chen, Jack Jia Hua; Vitale, Olivia Hope; Lao, Yanbin; Estwick, Selina; Qi, Zhonghua; ElSayed, Mohamed E H","year":2023,"journal":"Molecular pharmaceutics, 20(2), 929-941","doi":"10.1021/acs.molpharmaceut.2c00443","pmid":"36592951","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07473","title":"Dual-targeting exosomes for improved drug delivery in breast cancer.","authors":"Tran, Nam Hb; Nguyen, Diem Dn; Nguyen, Ngoc Mai; Tran, Chau; Nguyen Thi, Ngoc Thanh; Ho, Duyen Tk; Nguyen, Hoai-Nghia; Tu, Lan N","year":2023,"journal":"Nanomedicine (London, England), 18(7), 599-611","doi":"10.2217/nnm-2022-0328","pmid":"37194929","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07474","title":"HIGH-FIBER DIET PROMOTES METABOLIC, HORMONAL, AND SATIETY EFFECTS IN OBESE WOMEN ON A SHORT-TERM CALORIC RESTRICTION.","authors":"Triffoni-Melo, Andresa de Toledo; Castro, Margaret de; Jordão, Alceu Afonso; Leandro-Merhi, Vânia Aparecida; Dick-DE-Paula, Ingrid; Diez-Garcia, Rosa Wanda","year":2023,"journal":"Arquivos de gastroenterologia, 60(2), 163-171","doi":"10.1590/S0004-2803.202302022-96","pmid":"37556741","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07475","title":"Gut hormone-based pharmacology: novel formulations and future possibilities for metabolic disease therapy.","authors":"Tschöp, Matthias; Nogueiras, Ruben; Ahrén, Bo","year":2023,"journal":"Diabetologia, 66(10), 1796-1808","doi":"10.1007/s00125-023-05929-0","pmid":"37209227","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07476","title":"The role of glucagon-like peptide-1 receptor agonists in nonalcoholic fatty liver disease.","authors":"Tsiampali, Chara; Papaioannidou, Paraskevi; Goulas, Antonis; Polyzos, Stergios A","year":2023,"journal":"Expert review of clinical pharmacology, 16(11), 1063-1072","doi":"10.1080/17512433.2023.2274536","pmid":"37864548","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Clinical studies show GLP-1 receptor agonists in NAFLD improve: liver function tests (ALT/AST), hepatic steatosis (fat accumulation) on histology, and hepatic inflammation on histology. However, they have not demonstrated improvement in liver fibrosis. The review suggests two key directions: early use in non-fibrotic NAFLD to prevent fibrosis progression, and combination therapy with other medications for advanced disease where additive or synergistic effects may be possible.","whyItMatters":"NAFLD has no FDA-approved treatment (at time of this review), and it's the fastest-growing cause of liver transplantation. GLP-1 drugs are already widely prescribed for diabetes and obesity — many of the same patients who have NAFLD. Understanding that these drugs help some but not all aspects of liver disease is critical for setting appropriate clinical expectations and designing combination treatment strategies.","specificNumbers":"","methodology":"Narrative review of selected clinical studies examining GLP-1 receptor agonist effects on NAFLD outcomes, including liver function tests and histological endpoints (steatosis, inflammation, fibrosis).","limitations":"This is a narrative review, not a systematic review or meta-analysis. The included studies varied in design, patient populations, GLP-1 drugs used, and outcome measures. Most studies had relatively short follow-up periods, which may be insufficient to detect fibrosis changes. The term NAFLD has since been updated to MASLD/MASH in clinical nomenclature. More recent data (post-2023) may have changed some conclusions."},{"rthcId":"RPEP-07477","title":"Development of Hydrophobic Cell-Penetrating Stapled Peptides as Drug Carriers.","authors":"Tsuchiya, Keisuke; Horikoshi, Kanako; Fujita, Minami; Hirano, Motoharu; Miyamoto, Maho; Yokoo, Hidetomo; Demizu, Yosuke","year":2023,"journal":"International journal of molecular sciences, 24(14)","doi":"10.3390/ijms241411768","pmid":"37511527","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07478","title":"Natriuretic Peptides: Role in the Diagnosis and Management of Heart Failure: A Scientific Statement From the Heart Failure Association of the European Society of Cardiology, Heart Failure Society of America and Japanese Heart Failure Society.","authors":"Tsutsui, Hiroyuki; Albert, Nancy M; Coats, Andrew J S; Anker, Stefan D; Bayes-Genis, Antoni; Butler, Javed; Chioncel, Ovidiu; Defilippi, Christopher R; Drazner, Mark H; Felker, G Michael; Filippatos, Gerasimos; Fiuzat, Mona; Ide, Tomomi; Januzzi, James L; Kinugawa, Koichiro; Kuwahara, Koichiro; Matsue, Yuya; Mentz, Robert J; Metra, Marco; Pandey, Ambarish; Rosano, Giuseppe; Saito, Yoshihiko; Sakata, Yasushi; Sato, Naoki; Seferovic, Petar M; Teerlink, John; Yamamoto, Kazuhiro; Yoshimura, Michihiro","year":2023,"journal":"Journal of cardiac failure, 29(5), 787-804","doi":"10.1016/j.cardfail.2023.02.009","pmid":"37117140","tags":["cardiovascular-peptides","peptide-biomarkers"],"studyType":"consensus-statement","evidenceStrength":"high","keyFinding":"This trilateral scientific statement from the European, American, and Japanese heart failure societies provides a comprehensive framework for how natriuretic peptides — specifically BNP and NT-proBNP — should be used in diagnosing and managing heart failure. The document covers four major areas: the biology and cardiovascular protective effects of natriuretic peptides; their established role as diagnostic and prognostic biomarkers in both acute and chronic heart failure; their use as endpoints in clinical trials and as guides for therapy adjustment; and their direct therapeutic applications through drugs like nesiritide (recombinant BNP), carperitide (ANP), and ARNIs (sacubitril/valsartan).\n\nThe statement emphasizes that with the development of ARNIs — which work by preventing the breakdown of natriuretic peptides — these peptides have gained importance not just as biomarkers but as therapeutic agents in their own right.","whyItMatters":"Natriuretic peptides are the single most important blood test in heart failure diagnosis. This consensus statement from three major international societies represents the authoritative global perspective on how to use them — from initial diagnosis to guiding treatment decisions. The emergence of ARNI therapy (sacubitril/valsartan) has transformed natriuretic peptides from passive biomarkers into active therapeutic targets, making this framework especially relevant.","specificNumbers":"Consensus from 3 international societies · Covers BNP + NT-proBNP · 4 focus areas: biology, biomarkers, therapy, future directions · 28 expert authors","methodology":"Expert consensus scientific statement developed through the Trilateral Cooperation Project among the Heart Failure Association of the European Society of Cardiology, Heart Failure Society of America, and Japanese Heart Failure Society. Synthesizes existing evidence across diagnosis, prognosis, clinical trials, and therapeutics.","limitations":"As a consensus statement rather than a systematic review, it reflects expert opinion and may be subject to selection bias in evidence cited. Clinical practice recommendations may vary by region and healthcare system. Rapidly evolving therapeutics may outpace some recommendations."},{"rthcId":"RPEP-07479","title":"Natriuretic peptides: role in the diagnosis and management of heart failure: a scientific statement from the Heart Failure Association of the European Society of Cardiology, Heart Failure Society of America and Japanese Heart Failure Society.","authors":"Tsutsui, Hiroyuki; Albert, Nancy M; Coats, Andrew J S; Anker, Stefan D; Bayes-Genis, Antoni; Butler, Javed; Chioncel, Ovidiu; Defilippi, Christopher R; Drazner, Mark H; Felker, G Michael; Filippatos, Gerasimos; Fiuzat, Mona; Ide, Tomomi; Januzzi, James L; Kinugawa, Koichiro; Kuwahara, Koichiro; Matsue, Yuya; Mentz, Robert J; Metra, Marco; Pandey, Ambarish; Rosano, Giuseppe; Saito, Yoshihiko; Sakata, Yasushi; Sato, Naoki; Seferovic, Petar M; Teerlink, John; Yamamoto, Kazuhiro; Yoshimura, Michihiro","year":2023,"journal":"European journal of heart failure, 25(5), 616-631","doi":"10.1002/ejhf.2848","pmid":"37098791","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"This trilateral scientific statement from three major heart failure societies provides a comprehensive framework for natriuretic peptides (BNP and NT-proBNP) in heart failure management. Key roles include: (1) BNP/NT-proBNP as the primary diagnostic biomarkers for heart failure with complementary prognostic value, (2) natriuretic peptide-guided therapy to optimize treatment, and (3) therapeutic applications including nesiritide (recombinant BNP), carperitide (ANP), and angiotensin receptor-neprilysin inhibitors (ARNIs like sacubitril/valsartan) that work by increasing endogenous natriuretic peptide levels.","whyItMatters":"Natriuretic peptides have evolved from simple diagnostic biomarkers to playing a central therapeutic role in heart failure management. The introduction of ARNIs — which boost natriuretic peptide levels by inhibiting their breakdown — has transformed heart failure treatment and underscored the direct cardiovascular protective properties of these peptides. This consensus statement from three international heart failure societies establishes the definitive framework for how natriuretic peptides should be used in clinical practice.","specificNumbers":"","methodology":"Expert consensus statement developed through the Trilateral Cooperation Project among the Heart Failure Association of the European Society of Cardiology, the Heart Failure Society of America, and the Japanese Heart Failure Society. The document synthesizes evidence from basic research, clinical trials (including trials using natriuretic peptides as inclusion criteria or endpoints), and therapeutic studies.","limitations":"As a consensus statement rather than a systematic review or meta-analysis, the document reflects expert interpretation of existing evidence. Specific gaps in knowledge are acknowledged, including optimal natriuretic peptide thresholds across different populations, the role of natriuretic peptide-guided therapy in HF with preserved ejection fraction, and the impact of obesity and renal dysfunction on natriuretic peptide levels."},{"rthcId":"RPEP-07480","title":"Indicators of Kidney Fibrosis in Patients with Type 2 Diabetes and Chronic Kidney Disease Treated with Dulaglutide.","authors":"Tuttle, Katherine R; Wilson, Jonathan Matthew; Lin, Yanzhu; Qian, Hui-Rong; Genovese, Federica; Karsdal, Morten Asser; Duffin, Kevin L; Botros, Fady T","year":2023,"journal":"American journal of nephrology, 54(1-2), 74-82","doi":"10.1159/000529374","pmid":"36754023","tags":[],"studyType":"post-hoc-analysis","evidenceStrength":"moderate","keyFinding":"In this post-hoc analysis from the AWARD-7 trial, the GLP-1 agonist dulaglutide showed biomarker evidence of reducing kidney fibrosis compared to insulin glargine in type 2 diabetes patients with CKD. Specifically:\n\n- Serum PRO-C6 (a marker of new scar tissue formation — type VI collagen) decreased with dulaglutide but increased with insulin glargine at both 26 and 52 weeks (p<0.01)\n- Urine C3M (a marker of scar tissue breakdown — type III collagen degradation) increased with dulaglutide but decreased with insulin glargine (p<0.05)\n\nThis combination — less new fibrosis plus more scar tissue clearance — suggests dulaglutide may actively reverse kidney scarring, not just slow its progression. The effects were more pronounced in patients with macroalbuminuria (severe kidney damage). Both fibrosis biomarkers correlated with kidney function (eGFR), supporting their clinical relevance.","whyItMatters":"Kidney fibrosis (scarring) is the final common pathway to kidney failure — once enough scar tissue accumulates, the kidney can't function. Until now, we could slow fibrosis but couldn't reverse it. This study provides the first biomarker evidence that a GLP-1 agonist may actually reduce kidney scarring at the molecular level, not just slow kidney function decline. If confirmed, this adds a powerful mechanistic explanation for why GLP-1 drugs protect kidneys in trials like FLOW.","specificNumbers":"N=330 analyzed · 52-week treatment · PRO-C6 (fibrosis): -4.6% dulaglutide vs +5.7% insulin (week 26, p<0.01) · C3M (scar breakdown): +10.9% dulaglutide vs -10.0% insulin (week 26, p<0.05) · Greater effects in macroalbuminuria subgroup · Both markers correlated with eGFR","methodology":"This was an exploratory post-hoc analysis of the AWARD-7 randomized trial comparing dulaglutide 1.5 mg weekly to insulin glargine in 330 patients with type 2 diabetes and moderate-to-severe CKD. Two collagen-based fibrosis biomarkers were measured using ELISA assays: serum PRO-C6 (type VI collagen formation, reflecting new fibrosis) and urine C3M (type III collagen degradation, reflecting scar breakdown). Changes were analyzed using mixed-effects models and correlated with eGFR outcomes.","limitations":"This is a post-hoc exploratory analysis — the AWARD-7 trial was not designed to test kidney fibrosis as a primary outcome, so these findings are hypothesis-generating. The biomarkers are surrogate measures of fibrosis, not direct tissue measurements (which would require kidney biopsies). The comparison is against insulin glargine rather than placebo, making it unclear whether dulaglutide is reducing fibrosis or insulin is increasing it. The sample size of 330 is moderate for biomarker analyses."},{"rthcId":"RPEP-07481","title":"Systems Biology and Peptide Engineering to Overcome Absorption Barriers for Oral Peptide Delivery: Dosage Form Optimization Case Study Preceding Clinical Translation.","authors":"Tyagi, Puneet; Patel, Chandresh; Gibson, Kimberly; MacDougall, Fiona; Pechenov, Sergei Y; Will, Sarah; Revell, Jefferson; Huang, Yue; Rosenbaum, Anton I; Balic, Kemal; Maharoof, Umar; Grimsby, Joseph; Subramony, J Anand","year":2023,"journal":"Pharmaceutics, 15(10)","doi":"10.3390/pharmaceutics15102436","pmid":"37896196","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07482","title":"Peptide hydrolysate from fish skin collagen to prevent and treat Aeromonas hydrophila infection in Oreochromis niloticus.","authors":"Ulzanah, Nida; Wahjuningrum, Dinamella; Widanarni, Widanarni; Kusumaningtyas, Eni","year":2023,"journal":"Veterinary research communications, 47(2), 487-494","doi":"10.1007/s11259-022-09969-6","pmid":"36229726","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07483","title":"Peptide-Based Vectors: A Biomolecular Engineering Strategy for Gene Delivery.","authors":"Urandur, Sandeep; Sullivan, Millicent O","year":2023,"journal":"Annual review of chemical and biomolecular engineering, 14, 243-264","doi":"10.1146/annurev-chembioeng-101121-070232","pmid":"36888991","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07484","title":"Therapy targeting antigen-specific T cells by a peptide-based tolerizing vaccine against autoimmune arthritis.","authors":"Urbonaviciute, Vilma; Romero-Castillo, Laura; Xu, Bingze; Luo, Huqiao; Schneider, Nadine; Weisse, Sylvia; Do, Nhu-Nguyen; Oliveira-Coelho, Ana; Fernandez Lahore, Gonzalo; Li, Taotao; Sabatier, Pierre; Beusch, Christian M; Viljanen, Johan; Zubarev, Roman A; Kihlberg, Jan; Bäcklund, Johan; Burkhardt, Harald; Holmdahl, Rikard","year":2023,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 120(25), e2218668120","doi":"10.1073/pnas.2218668120","pmid":"37307481","tags":["immunotherapy","autoimmune-disease"],"studyType":"preclinical","evidenceStrength":"preliminary","keyFinding":"Researchers developed a peptide-based tolerizing vaccine using a galactosylated collagen type II peptide bound to an MHC class II protein (Aq-galCOL2) that directly interacts with disease-driving T cells in autoimmune arthritis. The vaccine expanded a special population of VISTA-positive regulatory T cells that suppressed the autoimmune attack.\n\nCritically, the therapeutic effect was dominant — meaning the protective regulatory T cells could be transferred to other mice and still suppress arthritis. The approach also proved tissue-specific, working across multiple arthritis models including antibody-induced arthritis. This represents a fundamentally different strategy from current arthritis treatments, which broadly suppress the immune system rather than targeting only the disease-causing cells.","whyItMatters":"Current treatments for rheumatoid arthritis — like methotrexate and biologics — suppress the entire immune system, increasing infection risk. A tolerizing vaccine that only targets the specific T cells driving joint destruction would leave the rest of the immune system intact. This 'antigen-specific' approach has been a holy grail of autoimmune research for decades, and this study demonstrates it's achievable in principle, with potential applicability beyond arthritis to other autoimmune diseases.","specificNumbers":"","methodology":"The researchers engineered an MHC class II protein loaded with a modified collagen peptide (galactosylated COL2) and administered it to mice with autoimmune arthritis models. They tracked the expansion of regulatory T cells, measured disease suppression, and performed adoptive transfer experiments — moving regulatory T cells from treated mice into untreated mice — to confirm the dominant, transferable nature of the immune tolerance. Multiple arthritis models were tested, including antibody-induced arthritis.","limitations":"This is entirely a mouse study — the MHC proteins used are specific to mice (Aq), and human translation would require matching human HLA molecules. The complexity of manufacturing MHC-peptide complexes for diverse human HLA types could be a significant barrier to clinical development. Long-term durability of the tolerogenic effect and safety in humans remain unknown."},{"rthcId":"RPEP-07485","title":"A case report of a chronic migraine patient treated with three different anti-CGRP monoclonal antibodies: which parameters better represent the efficacy?","authors":"Uzun, Sena; Frejvall, Ulf; Özkaya-Sahin, Gülsen; Sahin, Gürdal","year":2023,"journal":"Frontiers in neurology, 14, 1176816","doi":"10.3389/fneur.2023.1176816","pmid":"37213912","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07486","title":"A Case of Dulaglutide-Induced Vaginal Bleed.","authors":"Vaccaro, Christopher J; Zaidi, Syed Muhammad Hussain; Iskander, Peter A; McFadden, Erin","year":2023,"journal":"Cureus, 15(5), e38774","doi":"10.7759/cureus.38774","pmid":"37303364","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A 44-year-old perimenopausal woman with type 2 diabetes, who had previously been unable to tolerate metformin and semaglutide, experienced significant vaginal hemorrhage beginning one week after receiving her second dose of dulaglutide.\n\nThe bleeding was severe enough to cause a significant drop in hemoglobin concentration. Upon discontinuation of dulaglutide, the vaginal bleeding stopped, establishing a temporal relationship between the drug and the adverse event.\n\nThis represents a rare, previously unreported side effect of dulaglutide not identified during clinical trials.","whyItMatters":"With tens of millions of people now taking GLP-1 receptor agonists worldwide, rare side effects that weren't detected in clinical trials are increasingly being identified in the general population. This case underscores the importance of post-market surveillance and physician awareness of unusual adverse reactions, particularly as these drugs are prescribed to a broader range of patients than those studied in original trials.","specificNumbers":"","methodology":"Single-patient case report documenting the clinical course, temporal relationship between dulaglutide administration and symptom onset, resolution upon drug discontinuation, and the patient's medical history including prior intolerance to other diabetes medications.","limitations":"This is a single case report, which is the weakest form of clinical evidence. Temporal association (drug started → bleeding occurred → drug stopped → bleeding resolved) suggests but does not prove causation. The patient was perimenopausal, a period when irregular bleeding is common regardless of medication. No rechallenge was performed to confirm the drug was the cause. Other potential causes of vaginal bleeding were not fully detailed in the abstract. A single case cannot establish incidence rates."},{"rthcId":"RPEP-07487","title":"New Perspective for Using Antimicrobial and Cell-Penetrating Peptides to Increase Efficacy of Antineoplastic 5-FU in Cancer Cells.","authors":"Vale, Nuno; Ribeiro, Eduarda; Cruz, Inês; Stulberg, Valentina; Koksch, Beate; Costa, Bárbara","year":2023,"journal":"Journal of functional biomaterials, 14(12)","doi":"10.3390/jfb14120565","pmid":"38132819","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07488","title":"Lecanemab in Early Alzheimer's Disease.","authors":"van Dyck, Christopher H; Swanson, Chad J; Aisen, Paul; Bateman, Randall J; Chen, Christopher; Gee, Michelle; Kanekiyo, Michio; Li, David; Reyderman, Larisa; Cohen, Sharon; Froelich, Lutz; Katayama, Sadao; Sabbagh, Marwan; Vellas, Bruno; Watson, David; Dhadda, Shobha; Irizarry, Michael; Kramer, Lynn D; Iwatsubo, Takeshi","year":2023,"journal":"The New England journal of medicine, 388(1), 9-21","doi":"10.1056/NEJMoa2212948","pmid":"36449413","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07489","title":"Encapsulation in oleyl-modified hyaluronic acid nanogels substantially improves the clinical potential of the antimicrobial peptides SAAP-148 and Ab-Cath.","authors":"van Gent, Miriam E; Klodzinska, Sylvia N; Drijfhout, Jan Wouter; Nielsen, Hanne M; Nibbering, Peter H","year":2023,"journal":"European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 193, 254-261","doi":"10.1016/j.ejpb.2023.11.005","pmid":"37944710","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Encapsulation of antimicrobial peptides SAAP-148 and Ab-Cath in oleyl-modified hyaluronic acid (OL-HA) nanogels maintained their antimicrobial activity against drug-resistant Staphylococcus aureus and Acinetobacter baumannii while significantly reducing toxicity to human cells.\n\nThe selectivity index improved 2-fold for SAAP-148 and 16.8-fold for Ab-Cath. Ab-Cath-loaded nanogels achieved a selectivity index of ≥300 for S. aureus and ≥3,000 for A. baumannii — levels that indicate strong clinical potential. The nanogels were 181-206 nm in size with 53-63% encapsulation efficiency.","whyItMatters":"Antibiotic resistance is one of the biggest threats to global health, and antimicrobial peptides are a promising alternative — but their toxicity to healthy cells has been a major roadblock to clinical use. This nanogel delivery system addresses that core problem by dramatically improving the safety margin without sacrificing effectiveness, potentially bringing peptide-based antibiotics closer to real-world medical use.","specificNumbers":"","methodology":"The researchers created nanogels from oleyl-modified hyaluronic acid and loaded them with two antimicrobial peptides. They characterized the physical properties of the nanogels (size, surface charge, encapsulation efficiency) and tested their antimicrobial activity against drug-resistant S. aureus and A. baumannii in vitro. Toxicity was assessed against human red blood cells and primary skin fibroblasts to calculate selectivity indices comparing bacteria-killing to cell-damaging concentrations.","limitations":"This study was conducted entirely in laboratory settings (in vitro), so it remains unknown whether the nanogels would perform the same way in living organisms. The encapsulation efficiency of 53-63% means a significant portion of the peptide is not captured in the nanogels. Long-term stability, biodistribution, and potential immune responses to the nanogels were not assessed. The study tested only two bacterial species, so the approach may not generalize to all resistant pathogens."},{"rthcId":"RPEP-07490","title":"The transcription factor VAX1 in VIP neurons of the suprachiasmatic nucleus impacts circadian rhythm generation, depressive-like behavior, and the reproductive axis in a sex-specific manner in mice.","authors":"Van Loh, Brooke M; Yaw, Alexandra M; Breuer, Joseph A; Jackson, Brooke; Nguyen, Duong; Jang, Krystal; Ramos, Fabiola; Ho, Emily V; Cui, Laura J; Gillette, Dominique L M; Sempere, Lorenzo F; Gorman, Michael R; Tonsfeldt, Karen J; Mellon, Pamela L; Hoffmann, Hanne M","year":2023,"journal":"Frontiers in endocrinology, 14, 1269672","doi":"10.3389/fendo.2023.1269672","pmid":"38205198","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07491","title":"PS9, Derived from an Aquatic Fungus Virulent Protein, Glycosyl Hydrolase, Arrests MCF-7 Proliferation by Regulating Intracellular Reactive Oxygen Species and Apoptotic Pathways.","authors":"Velayutham, Manikandan; Sarkar, Purabi; Karuppiah, Kanchana M; Arumugam, Priyadharsan; Shajahan, Shanavas; Abu Haija, Mohammad; Ahamad, Tansir; Arasu, Mariadhas Valan; Al-Dhabi, Naif Abdullah; Choi, Ki-Choon; Guru, Ajay; Arockiaraj, Jesu","year":2023,"journal":"ACS omega, 8(21), 18543-18553","doi":"10.1021/acsomega.3c00336","pmid":"37273629","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07492","title":"177 Lu-DOTATATE (Lutathera) Therapy in 68 Ga-DOTATATE PET/CT-Negative Liver Metastases of a Neuroendocrine Tumor.","authors":"Ventura, David; Roll, Wolfgang; Kasper, Hans-Udo; Rahbar, Kambiz; Stegger, Lars","year":2023,"journal":"Clinical nuclear medicine, 48(12), e585-e587","doi":"10.1097/RLU.0000000000004888","pmid":"37883194","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A 73-year-old man with metastatic pancreatic neuroendocrine tumor had both PET-positive and PET-negative liver metastases on 68Ga-DOTATATE PET/CT. Biopsy of a PET-negative lesion confirmed well-differentiated (G2) metastasis with high somatostatin receptor expression, indicating the scan had produced a false-negative result.\n\nAfter initiating peptide receptor radionuclide therapy with 177Lu-DOTATATE (Lutathera), post-therapeutic scintigraphy revealed vigorous uptake of the therapeutic peptide even in the previously PET-negative liver metastases. Follow-up PET/CT demonstrated partial response to therapy across the treated lesions.","whyItMatters":"In standard practice, a negative PET scan for a specific lesion often means that lesion won't be targeted by therapy. This case challenges that assumption — showing that some PET-negative tumors can still respond to peptide receptor therapy. This has important implications for treatment decisions, as some patients with mixed PET-positive and PET-negative disease might benefit from PRRT even when not all metastases are visible on diagnostic imaging.","specificNumbers":"","methodology":"This is a clinical case report of a single 73-year-old male patient. The diagnostic workup included 68Ga-DOTATATE PET/CT, which identified both positive and negative liver lesions along with extrahepatic metastases. Histopathological biopsy of a PET-negative lesion was performed to rule out secondary malignancy. After confirming neuroendocrine origin with high somatostatin receptor expression, 177Lu-DOTATATE therapy was initiated with close monitoring of PET-negative lesions via post-therapeutic scintigraphy and follow-up PET/CT.","limitations":"This is a single case report, which represents the lowest level of clinical evidence. The findings may not be generalizable to other patients or tumor types. The reason for the discordance between diagnostic PET (negative) and therapeutic uptake (positive) is not fully explained. Quantitative uptake values were not reported. Long-term survival outcomes were not described."},{"rthcId":"RPEP-07493","title":"Retreating migraine patients in the second year with monoclonal antibodies anti-CGRP pathway: the multicenter prospective cohort RE-DO study.","authors":"Vernieri, Fabrizio; Brunelli, Nicoletta; Guerzoni, Simona; Iannone, Luigi Francesco; Baraldi, Carlo; Rao, Renata; Schiano di Cola, Francesca; Ornello, Raffaele; Cevoli, Sabina; Lovati, Carlo; Albanese, Maria; Perrotta, Armando; Cetta, Ilaria; Rossi, Sergio Soeren; Taranta, Valentina; Filippi, Massimo; Geppetti, Pierangelo; Sacco, Simona; Altamura, Claudia","year":2023,"journal":"Journal of neurology, 270(11), 5436-5448","doi":"10.1007/s00415-023-11872-2","pmid":"37468621","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07494","title":"Unveiling the Role of Capping Groups in Naphthalene N-Capped Dehydrodipeptide Hydrogels.","authors":"Vilaça, Helena; Carvalho, André; Castro, Tarsila; Castanheira, Elisabete M S; Hilliou, Loic; Hamley, Ian; Melle-Franco, Manuel; Ferreira, Paula M T; Martins, José A","year":2023,"journal":"Gels (Basel, Switzerland), 9(6)","doi":"10.3390/gels9060464","pmid":"37367135","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07495","title":"Detection of the growth hormone secretagogue MK-0677 in equine hair following oral administration.","authors":"Viljanto, Marjaana; Cutler, Charlotte; Taylor, Polly; Habershon-Butcher, Jocelyn; Gray, Bob","year":2023,"journal":"Drug testing and analysis, 15(3), 361-367","doi":"10.1002/dta.3406","pmid":"36354265","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07496","title":"CDNF overexpression prevents motor-cognitive dysfunction by intrastriatal CPP-based delivery system in a Parkinson's disease animal model.","authors":"Villa-Cedillo, Sheila A; Matta-Yee-Chig, Daniel; Soto-Domínguez, Adolfo; Rodríguez-Rocha, Humberto; García-García, Aracely; Montes-de-Oca-Saucedo, Carlos R; Loera-Arias, María de Jesús; Valdés, Jesús; Saucedo-Cárdenas, Odila","year":2023,"journal":"Neuropeptides, 102, 102385","doi":"10.1016/j.npep.2023.102385","pmid":"37837805","tags":[],"studyType":"animal-study","evidenceStrength":"low","keyFinding":"A cell-penetrating peptide (CPP) based delivery system successfully delivered CDNF gene therapy directly into the brains of mice with Parkinson's-like disease, preventing both motor and cognitive dysfunction. The delivery vehicle — a modified rabies virus glycoprotein peptide (mRVG9R) with an Asn194Lys mutation that improves cell penetration — carried the CDNF gene into the striatum, where it protected dopaminergic neurons and oligodendrocytes from paraquat-induced toxicity.\n\nThe gene therapy also inhibited astrogliosis and microglial activation (brain inflammation), safeguarding the entire nigrostriatal pathway. Injections on days 0 and 20 were sufficient to protect against 6 weeks of paraquat-induced neurodegeneration.","whyItMatters":"Parkinson's disease has no treatment that prevents the underlying loss of dopamine neurons. Neurotrophic factors like CDNF can protect these neurons, but getting them into the brain is the challenge. This study shows that a cell-penetrating peptide can serve as a non-viral gene delivery vehicle, eliminating the need for viral vectors while still getting neuroprotective genes where they need to go.","specificNumbers":"2 intrastriatal injections (days 0 and 20) · 6 weeks of paraquat challenge · Preserved motor + cognitive function · Reduced astrogliosis + microglia activation · Protected dopaminergic neurons + oligodendrocytes","methodology":"Mice received two intrastriatal injections of the mRVG9R-KP-CDNF complex (days 0 and 20). Parkinson's-like disease was induced by intraperitoneal paraquat injections twice weekly for 6 weeks. Researchers assessed motor function (movement tests), cognitive function, and performed brain cell analysis including evaluation of dopaminergic neurons, oligodendrocytes, astrocyte activation, and microglial activation.","limitations":"Paraquat-induced PD model doesn't fully replicate human Parkinson's disease, which develops slowly over decades from multiple causes. The study doesn't report long-term outcomes beyond the 6-week treatment window. The number of mice per group isn't specified in the abstract. Direct brain injection (intrastriatal) is invasive and may not be practical for clinical use."},{"rthcId":"RPEP-07497","title":"The potential role of GLP-1 receptor agonist targeting in fertility-sparing treatment in obese patients with endometrial malignant pathology: a call for research.","authors":"Violette, Caroline J; Agarwal, Ravi; Mandelbaum, Rachel S; González, José L; Hong, Kurt M; Roman, Lynda D; Klar, Maximilan; Wright, Jason D; Paulson, Richard J; Obermair, Andreas; Matsuo, Koji","year":2023,"journal":"Expert review of anticancer therapy, 23(4), 385-395","doi":"10.1080/14737140.2023.2194636","pmid":"36944434","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07498","title":"The Study of Cell-Penetrating Peptides to Deliver dsRNA and siRNA by Feeding in the Desert Locust, Schistocerca gregaria.","authors":"Vogel, Elise; Santos, Dulce; Huygens, Cissy; Peeters, Paulien; Van den Brande, Stijn; Wynant, Niels; Vanden Broeck, Jozef","year":2023,"journal":"Insects, 14(7)","doi":"10.3390/insects14070597","pmid":"37504603","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07499","title":"How cardiologists can manage excess body weight and related cardiovascular risk. An expert opinion.","authors":"Volpe, Massimo; Borghi, Claudio; Cameli, Matteo; Cianflone, Domenico; Cittadini, Antonio; Maggioni, Aldo Pietro; Filardi, Pasquale Perrone; Rosano, Giuseppe; Senni, Michele; Sinagra, Gianfranco","year":2023,"journal":"International journal of cardiology, 381, 101-104","doi":"10.1016/j.ijcard.2023.03.054","pmid":"37001648","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07500","title":"RNAi-mediated gene silencing of Phlebotomus papatasi defensins favors Leishmania major infection.","authors":"Vomáčková Kykalová, Barbora; Sassù, Fabiana; Volf, Petr; Telleria, Erich Loza","year":2023,"journal":"Frontiers in physiology, 14, 1182141","doi":"10.3389/fphys.2023.1182141","pmid":"37265840","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07501","title":"Therapeutic inertia related to the injectable glucagon-like peptide-1 receptor agonists dulaglutide and semaglutide in patients with type 2 diabetes in UK primary care.","authors":"von Arx, Lill-Brith; Rachman, Jonathan; Webb, Joanne; Casey, Caroline; Patel, Amisha; Diomatari, Christina; Wood, Robert; Idris, Iskandar","year":2023,"journal":"Diabetes, obesity & metabolism, 25(5), 1331-1340","doi":"10.1111/dom.14985","pmid":"36692268","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07502","title":"PACAP and VIP Neuropeptides' and Receptors' Effects on Appetite, Satiety and Metabolism.","authors":"Vu, John P; Luong, Leon; Sanford, Daniel; Oh, Suwan; Kuc, Alma; Pisegna, Rita; Lewis, Michael; Pisegna, Joseph R; Germano, Patrizia M","year":2023,"journal":"Biology, 12(7)","doi":"10.3390/biology12071013","pmid":"37508442","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"PACAP and VIP act through three receptors (VPAC1R, VPAC2R, PAC1R) distributed in both the central nervous system and gastrointestinal tract to regulate appetite, satiety, calorie intake, energy expenditure, and fat accumulation. The review synthesizes evidence showing these peptides modulate body phenotype, metabolism, and homeostatic functions through both central (brain) and peripheral (gut, immune) pathways. Their widespread distribution and multi-organ effects position them as potential therapeutic targets for obesity and metabolic syndrome.","whyItMatters":"While GLP-1 drugs have transformed obesity treatment, the PACAP/VIP system represents an additional neuropeptide pathway that could complement or extend existing therapies. Understanding how these peptides regulate energy balance through parallel brain and gut mechanisms could reveal new drug targets, particularly for patients who don't respond adequately to GLP-1-based approaches.","specificNumbers":"","methodology":"Narrative review synthesizing recent data on PACAP, VIP, and their receptor subtypes' effects on appetite, satiety, metabolism, calorie intake, and fat accumulation from both central and peripheral signaling studies.","limitations":"As a review, the paper synthesizes existing literature without presenting new data. Much of the evidence for PACAP/VIP effects on metabolism comes from animal models. The translation of receptor-specific findings to human therapeutic applications is uncertain. The review acknowledges that the mechanisms regulating appetite and energy balance through these peptides are not fully elucidated. No PACAP/VIP-targeted obesity drugs are currently in clinical development."},{"rthcId":"RPEP-07503","title":"Predicting the survival probability of functional neuroendocrine tumors treated with peptide receptor radionuclide therapy: Serbian experience.","authors":"Vukomanovic, Vladimir; Nedic, Katarina Vuleta; Radojevic, Marija Zivkovic; Dagovic, Aleksandar; Milosavljevic, Neda; Markovic, Marina; Ignjatovic, Vladimir; Simic Vukomanovic, Ivana; Djukic, Svetlana; Sreckovic, Marijana; Backovic, Milena; Vuleta, Marko; Djukic, Aleksandar; Vukicevic, Verica; Ignjatovic, Vesna","year":2023,"journal":"Frontiers in endocrinology, 14, 1270421","doi":"10.3389/fendo.2023.1270421","pmid":"38317712","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07504","title":"Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: the SURMOUNT-3 phase 3 trial.","authors":"Wadden, Thomas A; Chao, Ariana M; Machineni, Sriram; Kushner, Robert; Ard, Jamy; Srivastava, Gitanjali; Halpern, Bruno; Zhang, Shuyu; Chen, Jiaxun; Bunck, Mathijs C; Ahmad, Nadia N; Forrester, Tammy","year":2023,"journal":"Nature medicine, 29(11), 2909-2918","doi":"10.1038/s41591-023-02597-w","pmid":"37840095","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07505","title":"Obesity medication lorcaserin activates brainstem GLP-1 neurons to reduce food intake and augments GLP-1 receptor agonist induced appetite suppression.","authors":"Wagner, Stefan; Brierley, Daniel I; Leeson-Payne, Alasdair; Jiang, Wanqing; Chianese, Raffaella; Lam, Brian Y H; Dowsett, Georgina K C; Cristiano, Claudia; Lyons, David; Reimann, Frank; Gribble, Fiona M; Martinez de Morentin, Pablo B; Yeo, Giles S H; Trapp, Stefan; Heisler, Lora K","year":2023,"journal":"Molecular metabolism, 68, 101665","doi":"10.1016/j.molmet.2022.101665","pmid":"36592795","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07506","title":"Mitochondria-derived peptide MOTS-c: effects and mechanisms related to stress, metabolism and aging.","authors":"Wan, Wei; Zhang, Lieliang; Lin, Yue; Rao, Xiuqing; Wang, Xifeng; Hua, Fuzhou; Ying, Jun","year":2023,"journal":"Journal of translational medicine, 21(1), 36","doi":"10.1186/s12967-023-03885-2","pmid":"36670507","tags":["mots-c","aging"],"studyType":"review","evidenceStrength":"expert-review","keyFinding":"MOTS-c is a peptide encoded by mitochondrial DNA (specifically within the 12S rRNA gene) that acts as a signaling molecule between mitochondria and the cell nucleus. When activated by stress or exercise, MOTS-c moves to the nucleus and turns on genes with antioxidant response elements (ARE) that help cells adapt to stress.\n\nIts primary mechanism involves the Folate-AICAR-AMPK pathway — the same master energy-sensing pathway activated by exercise and the diabetes drug metformin. Through this pathway, MOTS-c influences energy metabolism, insulin sensitivity, inflammation, exercise response, and multiple age-related diseases. The review positions MOTS-c as a key molecule for maintaining the balance between energy production and stress resistance that deteriorates during aging.","whyItMatters":"MOTS-c is part of a newly discovered class of mitochondrial-derived peptides that challenge the old view of mitochondria as simple energy factories. The fact that mitochondria produce signaling peptides that travel to the nucleus and regulate gene expression represents a fundamental shift in cell biology. For aging research specifically, MOTS-c is exciting because it connects exercise, metabolism, and stress resistance through a single molecular pathway — potentially explaining why exercise is so protective against age-related disease and opening new therapeutic possibilities.","specificNumbers":"Encoded by mitochondrial 12S rRNA gene · Acts via Folate-AICAR-AMPK pathway · Regulates antioxidant response element (ARE) genes · Influences insulin resistance, inflammation, metabolism, aging","methodology":"Comprehensive review article synthesizing published research on MOTS-c's molecular mechanisms, including its retrograde signaling to the nucleus, AMPK pathway activation, metabolic effects, stress homeostasis roles, and connections to aging-related diseases.","limitations":"As a review, this synthesizes existing research rather than presenting new data. Much of the MOTS-c research is preclinical (cell culture and animal studies). Human clinical data is limited. The precise mechanisms by which MOTS-c levels decline with age and how this contributes to disease are still being worked out. Therapeutic applications remain theoretical."},{"rthcId":"RPEP-07507","title":"Advancing oral delivery of biologics: Machine learning predicts peptide stability in the gastrointestinal tract.","authors":"Wang, Fanjin; Sangfuang, Nannapat; McCoubrey, Laura E; Yadav, Vipul; Elbadawi, Moe; Orlu, Mine; Gaisford, Simon; Basit, Abdul W","year":2023,"journal":"International journal of pharmaceutics, 634, 122643","doi":"10.1016/j.ijpharm.2023.122643","pmid":"36709014","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07508","title":"The antimicrobial peptide database is 20 years old: Recent developments and future directions.","authors":"Wang, Guangshun","year":2023,"journal":"Protein science : a publication of the Protein Society, 32(10), e4778","doi":"10.1002/pro.4778","pmid":"37695921","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07509","title":"H2O2 enhances the spontaneous phasic contractions of isolated human-bladder strips via activation of TRPA1 channels on sensory nerves and the release of substance P and PGE2.","authors":"Wang, Haoyu; Zhao, Mengmeng; Liu, Jiaxin; Liu, Lei; Liu, Hanwen; Ding, Ning; Wen, Jiliang; Wang, Shaoyong; Ge, Nan; Zhang, Xiulin","year":2023,"journal":"Free radical biology & medicine, 209(Pt 1), 1-8","doi":"10.1016/j.freeradbiomed.2023.10.001","pmid":"37802373","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07510","title":"Hypermethylation of thymosin β4 predicts a poor prognosis for patients with acute-on-chronic hepatitis B liver failure.","authors":"Wang, He; Yin, Yan-Ping; Wang, Zhen-Li; Qian, Yu; Fan, Yu-Chen; Liu, Hui-Hui; Wang, Kai","year":2023,"journal":"Hepatobiliary & pancreatic diseases international : HBPD INT, 22(4), 373-382","doi":"10.1016/j.hbpd.2022.08.005","pmid":"36041971","tags":[],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"Hypermethylation (epigenetic silencing) of the thymosin β4 (Tβ4) gene was significantly more common in patients with acute-on-chronic hepatitis B liver failure (ACHBLF) compared to those with pre-liver failure, chronic hepatitis B, or healthy controls. Tβ4 mRNA expression showed the opposite pattern — lower in more severe disease. The 3-month mortality rate was significantly higher in patients with methylated Tβ4 than unmethylated.\n\nCritically, Tβ4 methylation status outperformed the MELD score — the standard clinical tool — for predicting 1-, 2-, and 3-month disease incidence. Its predictive value was particularly strong for early and mid-stage liver failure, though not for advanced-stage disease.","whyItMatters":"Acute-on-chronic liver failure is a devastating condition with high mortality. The MELD score, currently the gold standard for predicting outcomes, has recognized limitations. Thymosin β4 is a peptide known for its roles in tissue repair, wound healing, and immune modulation. Discovering that its epigenetic silencing predicts poor outcomes better than MELD in early-stage disease could provide clinicians with a new biomarker for earlier, more accurate risk stratification — potentially enabling earlier intervention including liver transplant listing.","specificNumbers":"n=317 total · 115 ACHBLF patients · 80 pre-ACHBLF · 86 CHB · 36 healthy controls · Tβ4 methylation predicted 1-, 2-, 3-month outcomes better than MELD · Higher 3-month mortality in methylated group","methodology":"The study enrolled 115 patients with ACHBLF (further divided into early, mid, and advanced stages), 80 with pre-liver failure, 86 with chronic hepatitis B, and 36 healthy controls from a single university hospital. Tβ4 promoter methylation in peripheral blood mononuclear cells was assessed using methylation-specific PCR, and Tβ4 mRNA was quantified by real-time PCR. Prognostic value was compared against the MELD score for predicting 1-, 2-, and 3-month outcomes.","limitations":"This is a single-center observational study, which limits generalizability. The sample sizes within subgroups (especially the 33 early-stage patients) are relatively small. The study only examined hepatitis B-related liver failure, so findings may not apply to other causes of liver failure. External validation in independent cohorts is needed before clinical adoption."},{"rthcId":"RPEP-07511","title":"Hypomethylation of thymosin β4 promoter is associated with glucocorticoid therapy in patients with acute-on-chronic hepatitis B-induced liver failure.","authors":"Wang, He; Qian, Yu; Wang, Jing-Wen; Fang, Yu; Fan, Yu-Chen; Liu, Hui-Hui; Wang, Kai","year":2023,"journal":"International health, 15(1), 19-29","doi":"10.1093/inthealth/ihac003","pmid":"35150577","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07512","title":"GLP-1 receptor agonist, liraglutide, protects podocytes from apoptosis in diabetic nephropathy by promoting white fat browning.","authors":"Wang, Jiali; Zhou, Yanni; Long, Dan; Wu, Yucheng; Liu, Fang","year":2023,"journal":"Biochemical and biophysical research communications, 664, 142-151","doi":"10.1016/j.bbrc.2023.04.012","pmid":"37167707","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07513","title":"Antimicrobial peptide-producing dermal preadipocytes defend against Candida albicans skin infection via the FGFR-MEK-ERK pathway.","authors":"Wang, Jianing; Duan, Zhimin; Zeng, Rong; Yang, Lu; Liu, Weizhao; Liu, Yiman; Yao, Qian; Chen, Xu; Zhang, Ling-Juan; Li, Min","year":2023,"journal":"PLoS pathogens, 19(11), e1011754","doi":"10.1371/journal.ppat.1011754","pmid":"38032898","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07514","title":"Identification and In Silico Analysis of ACE-Inhibitory Peptides Derived from Milk Fermented by Lacticaseibacillus paracasei.","authors":"Wang, Jiaxu; Shao, Boyue; Li, Jiaxin; Wang, Zhimin; Zhang, Mixia; Jia, Lili; Yu, Pengfei; Ma, Chunli","year":2023,"journal":"Journal of agricultural and food chemistry, 71(33), 12462-12473","doi":"10.1021/acs.jafc.2c09148","pmid":"37578765","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07515","title":"Supramolecular salicylic acid ameliorates rosacea-like eruptions by suppressing NLRP3-mediated inflammasome activation in mice.","authors":"Wang, JingYu; Sun, Yan; Chen, LiangHong; Wang, YiChong; Shi, DongXin; Wu, Yan; Gao, XingHua","year":2023,"journal":"International immunopharmacology, 118, 110057","doi":"10.1016/j.intimp.2023.110057","pmid":"36989903","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07516","title":"GLP-1 Receptor Agonist Improves Mitochondrial Energy Status and Attenuates Nephrotoxicity In Vivo and In Vitro.","authors":"Wang, Linxi; Chen, Zhou; Liu, Xiaoying; Wang, Lijing; Zhou, Yu; Huang, Jingze; Liu, Zhiqing; Lin, Donghai; Liu, Libin","year":2023,"journal":"Metabolites, 13(11)","doi":"10.3390/metabo13111121","pmid":"37999218","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In vivo, 8 weeks of exenatide treatment regulated most metabolic abnormalities in diabetic rat kidneys as shown by NMR-based metabolomics. In vitro, exendin-4 restored mitochondrial functions in mesangial cells damaged by high-fat/high-glucose conditions: improved antioxidant capacity, increased the Bcl-2/Bax ratio (favoring cell survival over death), reduced cytochrome c release and caspase-3 activation (markers of programmed cell death). Energy metabolism was restored through increased succinate dehydrogenase and phosphofructokinase activities, increased glucose consumption, and inhibition of pyruvate dehydrogenase E1 activity.","whyItMatters":"Diabetic kidney disease is the leading cause of kidney failure worldwide. Current treatments slow progression but don't address the underlying mitochondrial dysfunction. This study reveals that GLP-1 drugs protect kidneys by restoring mitochondrial energy production and preventing cell death — mechanisms that go beyond simple blood sugar control. This supports the growing evidence that GLP-1 drugs offer kidney protection through direct cellular effects.","specificNumbers":"","methodology":"Researchers used both in vivo (diabetic rat model) and in vitro (mesangial cells exposed to high-fat/high-glucose conditions) approaches. Diabetic rats received exenatide for 8 weeks. Metabolomic profiling was performed using 1H-NMR spectroscopy. In vitro studies measured mitochondrial function parameters, antioxidant capacity, apoptosis markers (Bcl-2/Bax, cytochrome c, caspase-3), and metabolic enzyme activities (succinate dehydrogenase, phosphofructokinase, pyruvate dehydrogenase E1).","limitations":"The in vivo component used a rat diabetes model that may not fully replicate human diabetic nephropathy. The in vitro studies used mesangial cells under acute high-fat/high-glucose stress, which differs from chronic diabetic kidney disease. Specific quantitative improvements were not detailed in the abstract. The metabolomic analysis identified global metabolic changes but didn't pinpoint specific nephroprotective pathways beyond mitochondrial function."},{"rthcId":"RPEP-07517","title":"SIRT1-dependent deacetylation of Txnip H3K9ac is critical for exenatide-improved diabetic kidney disease.","authors":"Wang, Mei-Jun; Cai, Xiang; Liang, Ri-Ying; Zhang, En-Ming; Liang, Xiao-Qi; Liang, Hua; Fu, Chang; Zhou, An-Dong; Shi, Yi; Xu, Fen; Cai, Meng-Yin","year":2023,"journal":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 167, 115515","doi":"10.1016/j.biopha.2023.115515","pmid":"37742607","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07518","title":"Zoledronic acid and thymosin α1 elicit antitumor immunity against prostate cancer by enhancing tumor inflammation and cytotoxic T cells.","authors":"Wang, Sheng; Huang, Maohua; Chen, Minfeng; Sun, Zhiting; Jiao, Yubo; Ye, Geni; Pan, Jinghua; Ye, Wencai; Zhao, Jianfu; Zhang, Dongmei","year":2023,"journal":"Journal for immunotherapy of cancer, 11(6)","doi":"10.1136/jitc-2022-006381","pmid":"37295817","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07519","title":"Bio-orthogonal engineered peptide: A multi-functional strategy for the gene therapy of osteoporotic bone loss.","authors":"Wang, Wei; Wang, Qing; Yu, Lei; Ge, Gaoran; Liu, Xin; Gao, Ang; Wang, Guomin; Wu, Zhengwei; Bai, Jiaxiang; Wang, Huaiyu; Chu, Paul K; Geng, Dechun","year":2023,"journal":"Biomaterials, 302, 122352","doi":"10.1016/j.biomaterials.2023.122352","pmid":"37866014","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07520","title":"Efficacy and safety of adding once-weekly dulaglutide to basal insulin for inadequately controlled type 2 diabetes in Chinese patients (AWARD-CHN3): A randomized, double-blind, placebo-controlled, phase III trial.","authors":"Wang, Weimin; Yan, Xin; Cheng, Zhifeng; Zhang, Qiqi; Wang, Rui; Deng, Yuying; Ma, Jianhua; Zhu, Dalong","year":2023,"journal":"Diabetes, obesity & metabolism, 25(12), 3690-3699","doi":"10.1111/dom.15263","pmid":"37732487","tags":["glp-1-agonists","diabetes"],"studyType":"randomized-controlled-trial","evidenceStrength":"strong","keyFinding":"Adding once-weekly dulaglutide 1.5 mg to basal insulin glargine produced a 2.0% reduction in HbA1c from baseline at 28 weeks, compared to 1.1% with insulin glargine plus placebo — a highly significant difference of 1.0% (p<0.001). Notably, 75.9% of patients in the dulaglutide group achieved the target HbA1c below 7.0%, versus only 33.8% with placebo.\n\nDulaglutide also produced weight loss while the placebo group gained weight (difference: -1.2 kg, p<0.001), and fasting blood sugar dropped further with dulaglutide (difference: -0.8 mmol/L, p<0.001). Critically, hypoglycemia rates were similar between groups (29.2% vs. 31.3%), and no severe hypoglycemia events occurred in either group.","whyItMatters":"Many patients with type 2 diabetes cannot achieve adequate blood sugar control with basal insulin alone. This trial demonstrates that adding the GLP-1 peptide drug dulaglutide to insulin is highly effective in Chinese patients — an important finding given that China has the world's largest diabetes population. The combination achieved target HbA1c in over three-quarters of patients without increasing hypoglycemia risk, while also producing weight loss instead of the weight gain typically seen with insulin dose escalation.","specificNumbers":"n=291 · HbA1c reduction: -2.0% (dulaglutide) vs. -1.1% (placebo) · p<0.001 · 75.9% vs. 33.8% achieved HbA1c <7.0% · weight difference: -1.2 kg · fasting glucose difference: -0.8 mmol/L · hypoglycemia: 29.2% vs. 31.3% (NS) · zero severe hypoglycemia · 28-week treatment","methodology":"This was a phase III, randomized, double-blind, placebo-controlled trial (AWARD-CHN3) in Chinese patients with T2DM. 291 patients with HbA1c 7.0-11.0% on stable basal insulin glargine with metformin and/or acarbose were randomized 1:1 to receive add-on dulaglutide 1.5 mg once weekly or placebo once weekly for 28 weeks. The primary endpoint was change from baseline in HbA1c at Week 28.","limitations":"The trial was conducted exclusively in Chinese patients, so results may not generalize to all populations, though GLP-1 agonist efficacy has been well-established globally. The 28-week duration, while standard for diabetes trials, does not capture long-term outcomes. Only the 1.5 mg dose of dulaglutide was tested. All patients were also receiving metformin and/or acarbose, so the results reflect combination therapy settings."},{"rthcId":"RPEP-07521","title":"Thymosin β4, a potential marker of malignancy and prognosis in hepatocellular carcinoma.","authors":"Wang, Wen-Chao; Zhang, Xiao-Feng; Tang, Er-Jiang; Li, A-Jian; Chen, Lei; Wang, Jia-Qi; Ma, Jun-Yong; Zhang, Xiao-Feng; Sun, Bin","year":2023,"journal":"Scandinavian journal of gastroenterology, 58(4), 380-391","doi":"10.1080/00365521.2022.2136012","pmid":"36269095","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Thymosin β4 was identified in serum by MALDI-TOF mass spectrometry and validated in 540 subjects (274 HCC, 119 cirrhosis, 89 hepatitis, 58 healthy). Serum Tβ4 was significantly elevated in HCC patients. Diagnostic performance: AUROC for Tβ4 was 0.908 (95% CI 0.880-0.935) versus AFP at 0.712 (95% CI 0.662-0.762), with optimal cutoff at 1063.6 ng/mL. Elevated Tβ4 was significantly associated with tumor size (p=0.016) and vascular invasion (p=0.005). Survival was significantly shorter in Tβ4-positive patients (p<0.001). Cox regression confirmed Tβ4 as an independent prognostic factor.","whyItMatters":"Liver cancer is the third leading cause of cancer death worldwide, and late diagnosis is a major reason for poor outcomes. AFP, the current standard blood marker, misses about 30-40% of liver cancers. A blood test with 91% diagnostic accuracy (vs. 71% for AFP) could catch significantly more cancers early, when treatment is most effective. Thymosin β4's additional prognostic value adds to its clinical utility.","specificNumbers":"","methodology":"540 subjects enrolled across four groups: HCC (274), liver cirrhosis (119), hepatitis (89), and healthy volunteers (58). MALDI-TOF mass spectrometry was used for initial biomarker discovery from serum. Tβ4 expression was validated in HCC cell lines and tissue samples. Serum levels were measured and diagnostic performance evaluated by ROC analysis with comparison to AFP. Clinical correlations with tumor characteristics and survival were assessed. Cox regression identified independent prognostic factors.","limitations":"Single-center study, which limits generalizability. The biomarker discovery and validation were performed in the same cohort — external validation in independent populations is needed. The study was cross-sectional, so the utility of Tβ4 for longitudinal surveillance (serial testing over time) was not assessed. The mechanism by which Tβ4 is elevated in serum (tumor secretion vs. tissue destruction) was not fully characterized. Comparison was made to AFP alone, not to other emerging HCC markers like PIVKA-II."},{"rthcId":"RPEP-07522","title":"Characterization and mechanism of action of amphibian-derived wound-healing-promoting peptides.","authors":"Wang, Xiakun; Duan, Hongcheng; Li, Min; Xu, Wei; Wei, Lin","year":2023,"journal":"Frontiers in cell and developmental biology, 11, 1219427","doi":"10.3389/fcell.2023.1219427","pmid":"37397255","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identified 27 amphibian-derived peptides with wound-healing properties: 25 from frogs and 2 from salamanders (tylotoin and TK-CATH). These peptides range from 5-80 amino acid residues in length and have various structural features:\n\n- 9 peptides have intramolecular disulfide bonds (including tiger17, cathelicidin-NV, cathelicidin-DM, RL-QN15)\n- 7 peptides are amidated at the C-terminus (including temporin A, temporin B, esculentin-1a)\n- The remainder are linear peptides without modifications\n\nAll peptides efficiently accelerated wound healing or photodamage repair in animal models. Their mechanisms include promoting keratinocyte and fibroblast proliferation and migration, recruiting neutrophils and macrophages to wounds, and regulating immune responses. Notably, 6 peptides (MSI-1, Pse-T2, cathelicidin-DM, brevinin-2Ta, brevinin-2PN, DMS-PS2) were antimicrobial peptides that also promoted healing of infected wounds by clearing bacteria.","whyItMatters":"Chronic wounds and wound infections remain a significant healthcare burden, particularly for diabetic and elderly patients. Current wound-healing therapies have limitations, and antibiotic resistance makes infected wounds increasingly difficult to treat. Amphibian-derived peptides offer a dual advantage: they can both accelerate healing and fight infection simultaneously. Their small size makes them relatively easy and cheap to produce synthetically, which could translate to affordable wound-care products.","specificNumbers":"","methodology":"This is a comprehensive review article that systematically cataloged all characterized amphibian-derived wound-healing peptides from published literature. The authors summarized each peptide's structural features, source species, wound-healing efficacy in animal models, and mechanisms of action.","limitations":"All wound-healing evidence comes from mouse and rat models — no human clinical data exist for any of these peptides. Translation from rodent skin healing to human skin healing faces significant biological differences. The review does not address potential toxicity, allergenicity, or stability challenges that would need to be resolved for clinical use. Long-term effects and optimal delivery methods have not been established."},{"rthcId":"RPEP-07523","title":"Thymosin β4 Exerts a Cytoprotective Function and Attenuates Liver Injury in Murine Hepatic Sinusoidal Obstruction Syndrome after Hematopoietic Stem Cell Transplantation.","authors":"Wang, Xiangmin; Zhou, Yi; Sun, Qian; Zhang, Qing; Zhou, Hongyuan; Zhang, Jiaoli; Du, Yuwei; Wang, Yuhan; Yuan, Ke; Xu, Linyan; Zhang, Meng; Yan, Dongmei; Zeng, Lingyu; Xu, Kailin; Sang, Wei","year":2023,"journal":"Transplantation and cellular therapy, 29(8), 492.e1-492.e10","doi":"10.1016/j.jtct.2023.05.009","pmid":"37192732","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07524","title":"Microencapsulated Limosilactobacillus reuteri Encoding Lactoferricin-Lactoferrampin Targeted Intestine against Salmonella typhimurium Infection.","authors":"Wang, Xueying; Xie, Weichun; Cai, Limeng; Han, Chuang; Kuang, Hongdi; Shao, Yilan; Zhang, Senhao; Zhang, Qi; Li, Jiaxuan; Cui, Wen; Jiang, Yanping; Tang, Lijie","year":2023,"journal":"Nutrients, 15(24)","doi":"10.3390/nu15245141","pmid":"38140400","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07525","title":"Antimicrobial Properties and Mode of Action of Cryptdin-4, a Mouse α-Defensin Regulated by Peptide Redox Structures and Bacterial Cultivation Conditions.","authors":"Wang, Yi; Song, Yuchi; Yan, Shaonan; Hiramine, Rina; Ohnishi, Yuki; Yokoi, Yuki; Nakamura, Kiminori; Kikukawa, Takashi; Ayabe, Tokiyoshi; Aizawa, Tomoyasu","year":2023,"journal":"Antibiotics (Basel, Switzerland), 12(6)","doi":"10.3390/antibiotics12061047","pmid":"37370366","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07526","title":"Electroacupuncture Zusanli (ST36) Relieves Somatic Pain in Colitis Rats by Inhibiting Dorsal Root Ganglion Sympathetic-Sensory Coupling and Neurogenic Inflammation.","authors":"Wang, Yi-Li; Zhu, Hai-Yan; Lv, Xi-Qian; Ren, Xing-Ying; Peng, Ying-Chun; Qu, Jin-Yu; Shen, Xue-Fang; Sun, Ran; Xiao, Meng-Lu; Zhang, Hong; Chen, Zhao-Hui; Cong, Peng","year":2023,"journal":"Neural plasticity, 2023, 9303419","doi":"10.1155/2023/9303419","pmid":"36910013","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07527","title":"Dulaglutide Ameliorates Intrauterine Adhesion by Suppressing Inflammation and Epithelial-Mesenchymal Transition via Inhibiting the TGF-β/Smad2 Signaling Pathway.","authors":"Wang, Yifan; Wang, Yixiang; Wu, Yang; Wang, Yiqing","year":2023,"journal":"Pharmaceuticals (Basel, Switzerland), 16(7)","doi":"10.3390/ph16070964","pmid":"37513876","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07528","title":"Hypoglycemic medicines in the treatment of Alzheimer's disease: Pathophysiological links between AD and glucose metabolism.","authors":"Wang, Yixuan; Hu, Hao; Liu, Xinyu; Guo, Xiangyu","year":2023,"journal":"Frontiers in pharmacology, 14, 1138499","doi":"10.3389/fphar.2023.1138499","pmid":"36909158","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07529","title":"Dulaglutide provides protection against sepsis-induced lung injury in mice by inhibiting inflammation and apoptosis.","authors":"Wang, Yue; Deng, Fengyi; Zhong, Xing; Du, Yijun; Fan, Xingyu; Su, Hong; Pan, Tianrong","year":2023,"journal":"European journal of pharmacology, 949, 175730","doi":"10.1016/j.ejphar.2023.175730","pmid":"37062504","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In mice with LPS-induced sepsis (15 mg/kg), dulaglutide (0.6 mg/kg daily) produced multiple protective effects in the lungs:\n\n- Improved weight loss and reduced overall lung injury\n- Reversed increases in six inflammatory mediators: IL-1β, TNF-α, IL-6, CXCL1, CCL2, and CXCL2\n- Reduced neutrophil and macrophage infiltration in lung tissues\n- Reversed apoptosis markers: reduced caspase-3, cleaved caspase-3, caspase-8 expression; restored Bcl-2/Bax ratio; reduced TUNEL-positive (dying) cells\n- Reduced expression of P-STAT3 (phosphorylated STAT3) and NLRP3 inflammasome — identified as potential therapeutic targets for sepsis lung injury\n\nThese results demonstrate dual anti-inflammatory and anti-apoptotic mechanisms of GLP-1 receptor activation in acute lung injury.","whyItMatters":"Sepsis kills approximately 11 million people annually worldwide, and acute lung injury is a leading cause of sepsis mortality. Current treatment is primarily supportive — there are no approved drugs that specifically target sepsis-induced lung damage. The discovery that a widely available GLP-1 drug protects lungs through specific molecular pathways (STAT3 and NLRP3) opens the possibility of repurposing existing diabetes medications for critical care, potentially saving lives with an already safety-tested drug.","specificNumbers":"","methodology":"Mice were given LPS (lipopolysaccharide, 15 mg/kg intraperitoneally daily) to induce sepsis-related acute lung injury. Dulaglutide (0.6 mg/kg daily intraperitoneally) was administered as treatment. Researchers measured body weight changes, lung tissue histopathology, inflammatory cytokine and chemokine expression (IL-1β, TNF-α, IL-6, CXCL1, CCL2, CXCL2), immune cell infiltration (neutrophils, macrophages), apoptosis markers (caspase-3, cleaved caspase-3, caspase-8, Bcl-2/Bax ratio), TUNEL staining for cell death, and signaling pathway proteins (P-STAT3, NLRP3).","limitations":"This is a mouse study using LPS injection to model sepsis, which differs from human sepsis caused by live bacterial infection. The LPS model produces a more predictable but less complex inflammatory response than actual sepsis. Dulaglutide was administered concurrently with LPS (prophylactic/treatment timing not clearly separated), so it's unclear whether the drug would work if given after sepsis is already established. The 0.6 mg/kg dose in mice may not translate directly to human dosing. No survival data were reported. The study did not assess whether dulaglutide affected bacterial clearance, which could be important in real sepsis."},{"rthcId":"RPEP-07530","title":"A bioengineered probiotic for the oral delivery of a peptide Kv1.3 channel blocker to treat rheumatoid arthritis.","authors":"Wang, Yuqing; Zhu, Duolong; Ortiz-Velez, Laura C; Perry, Jacob L; Pennington, Michael W; Hyser, Joseph M; Britton, Robert A; Beeton, Christine","year":2023,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 120(2), e2211977120","doi":"10.1073/pnas.2211977120","pmid":"36595694","tags":["peptide-delivery","antimicrobial-peptides"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Researchers engineered a probiotic bacterium (Lactobacillus reuteri) to produce and secrete ShK-235, a peptide that blocks the Kv1.3 potassium channel on inflammatory T cells. When fed to rats, a single oral dose delivered enough functional peptide into the bloodstream to reduce skin inflammation, and daily oral dosing dramatically reduced disease severity in a rat model of rheumatoid arthritis. The peptide did not trigger an immune response against itself, suggesting the probiotic delivery approach avoids the immunogenicity problems that plague many injected peptide drugs.","whyItMatters":"This study solves two major problems at once: oral delivery of a peptide (normally impossible because the gut destroys peptides) and targeted immunosuppression without broad immune shutdown. Using a probiotic as a living factory that continuously produces a therapeutic peptide in the gut is a creative approach that could transform how autoimmune diseases are treated — replacing daily injections with a simple oral dose.","specificNumbers":"","methodology":"The team genetically engineered L. reuteri to secrete the Kv1.3-blocking peptide ShK-235 on demand. They verified the secreted peptide blocked Kv1.3 channels and selectively inhibited inflammatory T cell proliferation in cell cultures. In rats, they tested single and daily oral doses against two disease models: delayed-type hypersensitivity (atopic dermatitis model) and a rheumatoid arthritis model, measuring clinical disease scores, joint inflammation, and anti-peptide antibody responses.","limitations":"This is an animal study in rats — translation to humans faces significant hurdles including regulatory approval of genetically modified probiotics, differences in human vs rat gut environments, and the need to verify adequate peptide absorption in humans. Long-term safety of colonization with engineered bacteria is unknown. The specific rat disease models don't perfectly replicate human rheumatoid arthritis."},{"rthcId":"RPEP-07531","title":"Anchoring of Polymer Loops on Enzyme-Immobilized Mesoporous ZIF-8 Enhances the Recognition Selectivity of Angiotensin-Converting Enzyme Inhibitory Peptides.","authors":"Wang, Zefen; Zhou, Qian; Liu, Siyuan; Liao, Dankui; Liu, Pengru; Lan, Xiongdiao","year":2023,"journal":"Molecules (Basel, Switzerland), 28(7)","doi":"10.3390/molecules28073117","pmid":"37049880","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07532","title":"Semaglutide ameliorates cognition and glucose metabolism dysfunction in the 3xTg mouse model of Alzheimer's disease via the GLP-1R/SIRT1/GLUT4 pathway.","authors":"Wang, Zhao-Jun; Li, Xin-Ru; Chai, Shi-Fan; Li, Wei-Ran; Li, Shuo; Hou, Meng; Li, Jia-Lei; Ye, Yu-Cai; Cai, Hong-Yan; Hölscher, Christian; Wu, Mei-Na","year":2023,"journal":"Neuropharmacology, 240, 109716","doi":"10.1016/j.neuropharm.2023.109716","pmid":"37730113","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07533","title":"Angiotensin-Converting Enzyme 2 Activation Is Not a Common Feature of Angiotensin-Converting Enzyme Inhibitory Peptides.","authors":"Wang, Zihan; Fan, Hongbing; Bao, Xiaoyu; Wu, Jianping","year":2023,"journal":"Journal of agricultural and food chemistry, 71(23), 8867-8876","doi":"10.1021/acs.jafc.2c04211","pmid":"37272779","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07534","title":"Mechanism of thymosin β4 in ameliorating liver fibrosis via the MAPK/NF-κB pathway.","authors":"Wang, Zilin; Zhang, Ya; Wang, Yinghui; Mou, Qiuju; Ren, Tingting; Zhu, Lili","year":2023,"journal":"Journal of biochemical and molecular toxicology, 37(7), e23338","doi":"10.1002/jbt.23338","pmid":"37211724","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Thymosin β4 (Tβ4) was downregulated in bile duct ligation (BDL) fibrotic mice and TGF-β1-induced LX-2 hepatic stellate cells. Tβ4 overexpression via lentiviral vectors: inhibited liver fibrosis in BDL mice (confirmed by HE and Masson staining), suppressed stellate cell migration and proliferation in TGF-β1-induced LX-2 cells, reduced ROS production, and blocked MAPK/NF-κB pathway activation (confirmed by reduced p-p38, p-ERK, p-JNK, and nuclear p65). Adding a MAPK activator (U-46619) reversed Tβ4's protective effects, while a MAPK inhibitor (SB203580) mimicked them — both in vitro and in vivo.","whyItMatters":"Liver fibrosis progresses to cirrhosis and liver failure, and no approved anti-fibrotic drugs exist for the liver. Thymosin β4 is already known to be safe in humans from wound healing studies, so identifying its anti-fibrotic mechanism could accelerate clinical development. The specific pathway identified (ROS → MAPK/NF-κB) provides clear molecular targets for therapeutic intervention.","specificNumbers":"","methodology":"Liver fibrosis mouse models were created by bile duct ligation (BDL) and validated by histological staining. TGF-β1-induced LX-2 hepatic stellate cells served as the in vitro model. Tβ4-overexpressing lentiviral vectors were used for gain-of-function studies. Outcomes measured: RT-qPCR for Tβ4 expression, Western blot for HSC activation markers and MAPK/NF-κB proteins, DCFH-DA for ROS, CCK-8 for proliferation, flow cytometry for cell cycle, Transwell for migration, and immunofluorescence for nuclear p65. MAPK activator and inhibitor experiments confirmed the pathway in both cells and BDL mice.","limitations":"The BDL model creates biliary-type fibrosis, which differs from the more common metabolic-associated and viral fibrosis in humans. Lentiviral overexpression achieves supraphysiological Tβ4 levels that may not reflect achievable therapeutic concentrations. The study focused on one signaling pathway, but fibrosis involves multiple interconnected pathways. LX-2 cells are an immortalized hepatic stellate cell line that may not fully represent primary cells. No dose-response relationship for Tβ4 was established."},{"rthcId":"RPEP-07535","title":"Thymalfasin therapy accelerates COVID-19 pneumonia rehabilitation through anti-inflammatory mechanisms.","authors":"Wang, Zirui; Wang, Cong; Fei, Xiaohua; Wu, Haixing; Niu, Peiqin; Shen, Changxing","year":2023,"journal":"Pneumonia (Nathan Qld.), 15(1), 14","doi":"10.1186/s41479-023-00116-6","pmid":"37743481","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07536","title":"Controlling the Self-Assembly and Material Properties of β-Sheet Peptide Hydrogels by Modulating Intermolecular Interactions.","authors":"Warren, James P; Culbert, Matthew P; Miles, Danielle E; Maude, Steven; Wilcox, Ruth K; Beales, Paul A","year":2023,"journal":"Gels (Basel, Switzerland), 9(6)","doi":"10.3390/gels9060441","pmid":"37367112","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07537","title":"A Phase 3, Randomized Trial of Bulevirtide in Chronic Hepatitis D.","authors":"Wedemeyer, Heiner; Aleman, Soo; Brunetto, Maurizia Rossana; Blank, Antje; Andreone, Pietro; Bogomolov, Pavel; Chulanov, Vladimir; Mamonova, Nina; Geyvandova, Natalia; Morozov, Viacheslav; Sagalova, Olga; Stepanova, Tatyana; Berger, Annemarie; Manuilov, Dmitry; Suri, Vithika; An, Qi; Da, Ben; Flaherty, John; Osinusi, Anu; Liu, Yang; Merle, Uta; Schulze Zur Wiesch, Julian; Zeuzem, Stefan; Ciesek, Sandra; Cornberg, Markus; Lampertico, Pietro","year":2023,"journal":"The New England journal of medicine, 389(1), 22-32","doi":"10.1056/NEJMoa2213429","pmid":"37345876","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07538","title":"Safety and efficacy of bulevirtide in combination with tenofovir disoproxil fumarate in patients with hepatitis B virus and hepatitis D virus coinfection (MYR202): a multicentre, randomised, parallel-group, open-label, phase 2 trial.","authors":"Wedemeyer, Heiner; Schöneweis, Katrin; Bogomolov, Pavel; Blank, Antje; Voronkova, Natalia; Stepanova, Tatiana; Sagalova, Olga; Chulanov, Vladimir; Osipenko, Marina; Morozov, Viacheslav; Geyvandova, Natalia; Sleptsova, Snezhana; Bakulin, Igor G; Khaertynova, Ilsiyar; Rusanova, Marina; Pathil, Anita; Merle, Uta; Bremer, Birgit; Allweiss, Lena; Lempp, Florian A; Port, Kerstin; Haag, Mathias; Schwab, Matthias; Zur Wiesch, Julian Schulze; Cornberg, Markus; Haefeli, Walter E; Dandri, Maura; Alexandrov, Alexander; Urban, Stephan","year":2023,"journal":"The Lancet. Infectious diseases, 23(1), 117-129","doi":"10.1016/S1473-3099(22)00318-8","pmid":"36113537","tags":["bulevirtide","hepatitis-d","antiviral-peptides"],"studyType":"randomized-controlled-trial","evidenceStrength":"moderate-high","keyFinding":"Bulevirtide, a first-in-class peptide entry inhibitor, significantly reduced hepatitis D virus (HDV) RNA levels when combined with tenofovir over 24 weeks. At the primary endpoint, 54% of patients on 2 mg bulevirtide, 50% on 5 mg, and 77% on 10 mg achieved either undetectable HDV RNA or a ≥2 log decline, compared to only 3% on tenofovir alone.\n\nThe 10 mg dose showed the strongest antiviral activity with a median 2.03 log10 decline in HDV RNA. However, HDV RNA rebounded after stopping bulevirtide, indicating the need for longer treatment. The drug was generally well tolerated, with asymptomatic bile salt increases being the most common side effect. No treatment-related deaths occurred.","whyItMatters":"Hepatitis D is the most severe form of viral hepatitis, affecting an estimated 12–72 million people worldwide, and until bulevirtide there was no approved targeted therapy. This trial provided key Phase 2 evidence supporting the conditional European approval of bulevirtide — the first peptide-based viral entry inhibitor for any hepatitis virus. It represents a completely new therapeutic approach: blocking the virus from entering liver cells rather than targeting viral replication.","specificNumbers":"n=120 · 3 dose groups + control · 10 mg: 77% response · 2 mg: 54% response · TDF alone: 3% response · Median HDV RNA decline: 2.03 log10 (10 mg) · 24-week treatment","methodology":"Multicentre, randomised, open-label, parallel-group Phase 2 trial (MYR202) across 16 hospitals in Germany and Russia. 120 adults with chronic hepatitis D (including 59 with cirrhosis) were randomized 1:1:1:1 to receive bulevirtide at 2 mg, 5 mg, or 10 mg subcutaneously daily plus oral tenofovir, or tenofovir alone, for 24 weeks. HDV RNA was monitored through week 48.","limitations":"Open-label design means neither patients nor doctors were blinded, which could introduce bias. The sample size of 120 patients is moderate for a Phase 2 trial. HDV RNA rebounded after treatment cessation, so durability of response with longer treatment is unknown. The study did not assess functional cure (HDV RNA clearance sustained off-treatment)."},{"rthcId":"RPEP-07539","title":"Gout Flares and Mortality After Sodium-Glucose Cotransporter-2 Inhibitor Treatment for Gout and Type 2 Diabetes.","authors":"Wei, Jie; Choi, Hyon K; Dalbeth, Nicola; Li, Xiaoxiao; Li, Changjun; Zeng, Chao; Lei, Guanghua; Zhang, Yuqing","year":2023,"journal":"JAMA network open, 6(8), e2330885","doi":"10.1001/jamanetworkopen.2023.30885","pmid":"37624597","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07540","title":"Temporospatial Expression of Neuropeptide Substance P in Dental Pulp Stem Cells During Odontoblastic Differentiation in Vitro and Reparative Dentinogenesis in Vivo.","authors":"Wei, Xiao-Lang; Luo, Ling; Chen, Meng-Zhu; Zhou, Jun; Lan, Bin-Yun; Ma, Xue-Meng; Chen, Wen-Xia","year":2023,"journal":"Journal of endodontics, 49(3), 276-285","doi":"10.1016/j.joen.2022.12.006","pmid":"36549466","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07541","title":"Thymosin α-1 in cancer therapy: Immunoregulation and potential applications.","authors":"Wei, Yiting; Zhang, Yunpeng; Li, Pengcheng; Yan, Chunguang; Wang, Lixin","year":2023,"journal":"International immunopharmacology, 117, 109744","doi":"10.1016/j.intimp.2023.109744","pmid":"36812669","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07542","title":"Complete Remission Upon Peptide Receptor Radionuclide Therapy in a G2 Pancreatic Neuroendocrine Tumor.","authors":"Weich, Alexander; Serfling, Sebastian E; Yi, Heqing; Buck, Andreas K; Higuchi, Takahiro; Werner, Rudolf A","year":2023,"journal":"Clinical nuclear medicine, 48(4), 335-336","doi":"10.1097/RLU.0000000000004537","pmid":"36728231","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07543","title":"Partial Response Upon Peptide Receptor Radionuclide Therapy in a Highly Proliferative Pancreatic Neuroendocrine Tumor.","authors":"Weich, Alexander; Serfling, Sebastian E; Rowe, Steven P; Solnes, Lilja B; Buck, Andreas K; Higuchi, Takahiro; Werner, Rudolf A","year":2023,"journal":"Clinical nuclear medicine, 48(6), 547-548","doi":"10.1097/RLU.0000000000004621","pmid":"36928302","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07544","title":"Walnut Protein: A Rising Source of High-Quality Protein and Its Updated Comprehensive Review.","authors":"Wen, Chaoting; Zhang, Zhiyi; Cao, Liyan; Liu, Guoyan; Liang, Li; Liu, Xiaofang; Zhang, Jixian; Li, Youdong; Yang, Xinquan; Li, Shugang; Ren, Jiaoyan; Xu, Xin","year":2023,"journal":"Journal of agricultural and food chemistry, 71(28), 10525-10542","doi":"10.1021/acs.jafc.3c01620","pmid":"37399339","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07545","title":"Production Technology and Functionality of Bioactive Peptides.","authors":"Wen, Qingmei; Zhang, Lei; Zhao, Feng; Chen, Yilu; Su, Yi; Zhang, Xiaochun; Chen, Pu; Zheng, Tao","year":2023,"journal":"Current pharmaceutical design, 29(9), 652-674","doi":"10.2174/1381612829666230201121353","pmid":"36725828","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07546","title":"A review on processing methods and functions of wheat germ-derived bioactive peptides.","authors":"Weng, Zebin; Chen, Yuanrong; Liang, Tingting; Lin, Yajuan; Cao, Hui; Song, Haizhao; Xiong, Ling; Wang, Fang; Shen, Xinchun; Xiao, Jianbo","year":2023,"journal":"Critical reviews in food science and nutrition, 63(22), 5577-5593","doi":"10.1080/10408398.2021.2021139","pmid":"34964419","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07547","title":"Comparison of the Usability, Accuracy, Preference, and Satisfaction of Three Once-Weekly Glucagon-Like Peptide 1 Receptor Agonist Pen Devices in People With Type 2 Diabetes.","authors":"Wettergreen, Sara A; Stewart, Morgan P; Kennedy, Katelyn; Trujillo, Jennifer M","year":2023,"journal":"Diabetes spectrum : a publication of the American Diabetes Association, 36(1), 5-13","doi":"10.2337/ds21-0108","pmid":"36818408","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07548","title":"Plasma Markers for Therapy Response Monitoring in Patients with Neuroendocrine Tumors Undergoing Peptide Receptor Radionuclide Therapy.","authors":"Wetz, Christoph; Ruhwedel, Tristan; Schatka, Imke; Grabowski, Jane; Jann, Henning; Metzger, Giulia; Galler, Markus; Amthauer, Holger; Rogasch, Julian M M","year":2023,"journal":"Cancers, 15(24)","doi":"10.3390/cancers15245717","pmid":"38136263","tags":[],"studyType":"retrospective","evidenceStrength":"moderate","keyFinding":"In 141 patients with metastatic neuroendocrine tumors undergoing peptide receptor radionuclide therapy (PRRT) with [177Lu]Lu-DOTATOC, rising alkaline phosphatase (ALP) levels during treatment were associated with significantly worse outcomes. Patients whose ALP decreased by more than 10% during PRRT had a median progression-free survival (PFS) of 24.3 months, compared to just 12.5 months for those whose ALP increased by more than 10%.\n\nProgression, relapse, or death occurred in 103 of 141 patients (73%). Significant ALP differences between patients with low vs. high PFS were detectable before the third and fourth treatment cycles, suggesting ALP could serve as an early warning marker during PRRT.","whyItMatters":"PRRT is one of the most important peptide-based cancer therapies, but clinicians lack reliable ways to monitor whether treatment is working during the course of therapy. This study identifies ALP changes as a simple, inexpensive blood marker that could help doctors identify patients who are responding poorly — potentially allowing earlier treatment adjustments.","specificNumbers":"","methodology":"Retrospective analysis of 141 patients with metastatic neuroendocrine tumors treated with [177Lu]Lu-DOTATOC PRRT at a single center. Laboratory values measured before each PRRT cycle were compared to pretherapeutic baselines. Changes in plasma markers were analyzed using Wilcoxon rank-sum tests, and survival outcomes were assessed using Kaplan-Meier analysis.","limitations":"This is a retrospective, single-center study, limiting generalizability. The analysis is exploratory and requires prospective validation. ALP can be influenced by many factors beyond tumor progression (liver function, bone metabolism), which could confound interpretation. The abstract notes that findings should be interpreted cautiously."},{"rthcId":"RPEP-07549","title":"Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity.","authors":"Wharton, Sean; Blevins, Thomas; Connery, Lisa; Rosenstock, Julio; Raha, Sohini; Liu, Rong; Ma, Xiaosu; Mather, Kieren J; Haupt, Axel; Robins, Deborah; Pratt, Edward; Kazda, Christof; Konig, Manige","year":2023,"journal":"The New England journal of medicine, 389(10), 877-888","doi":"10.1056/NEJMoa2302392","pmid":"37351564","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In this phase 2 NEJM trial, the oral GLP-1 pill orforglipron produced up to 14.7% body weight loss at 36 weeks in adults with obesity — compared to just 2.3% with placebo. At the highest dose (45 mg), 75% of participants lost at least 10% of their body weight. The drug also improved all prespecified cardiometabolic measures. Gastrointestinal side effects were the main issue, causing 10-17% of participants to discontinue, but these were mostly mild-to-moderate and occurred during the dose ramp-up period.","whyItMatters":"This is a landmark trial published in the New England Journal of Medicine — one of the first rigorous demonstrations that an oral, non-peptide GLP-1 drug can produce weight loss approaching what injectable semaglutide achieves. Because orforglipron is a small molecule (not a peptide), it doesn't need special absorption enhancers and can be taken as a simple daily pill. If confirmed in phase 3 trials, it could dramatically expand access to GLP-1-based weight loss treatment by removing the injection barrier.","specificNumbers":"","methodology":"This was a phase 2, randomized, double-blind, placebo-controlled trial. 272 adults with obesity (mean BMI 37.9, mean weight 108.7 kg) or overweight with weight-related conditions — and without diabetes — were randomized to one of four orforglipron doses (12, 24, 36, or 45 mg) or placebo, taken orally once daily for 36 weeks. The primary endpoint was percentage change in body weight at week 26, with week 36 as a secondary endpoint.","limitations":"This is a phase 2 trial with only 272 participants — large enough to establish efficacy signals but too small to detect rare adverse events. The 36-week duration doesn't address long-term safety or whether weight loss is maintained. Participants with diabetes were excluded, so results may not generalize to that population. The 10-17% discontinuation rate due to side effects across dose groups is notable."},{"rthcId":"RPEP-07550","title":"The Cardioprotective Effects of Semaglutide Exceed Those of Dietary Weight Loss in Mice With HFpEF.","authors":"Withaar, Coenraad; Meems, Laura M G; Nollet, Edgar E; Schouten, E Marloes; Schroeder, Marie A; Knudsen, Lotte B; Niss, Kristoffer; Madsen, Christian T; Hoegl, Annabelle; Mazzoni, Gianluca; van der Velden, Jolanda; Lam, Carolyn S P; Silljé, Herman H W; de Boer, Rudolf A","year":2023,"journal":"JACC. Basic to translational science, 8(10), 1298-1314","doi":"10.1016/j.jacbts.2023.05.012","pmid":"38094687","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07551","title":"Tirzepatide: A Dual Glucose-dependent Insulinotropic Polypeptide and Glucagon-Like Peptide-1 Agonist for the Management of Type 2 Diabetes Mellitus.","authors":"Wong, Elaine; Cope, Rebecca; Dima, Lorena; Nguyen, Timothy","year":2023,"journal":"American journal of therapeutics, 30(1), e26-e35","doi":"10.1097/MJT.0000000000001588","pmid":"36516422","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tirzepatide is a synthetic 39-amino-acid peptide based on the GIP sequence that acts as a dual GIP and GLP-1 receptor agonist. Across the SURPASS phase 3 trial program, tirzepatide consistently demonstrated significant HbA1c reductions and weight loss benefits as monotherapy and as add-on therapy to various antihyperglycemic drugs. The pharmacokinetics were similar in patients with kidney and hepatic impairment, with metabolites excreted through urine and feces. Common adverse events were gastrointestinal in nature.","whyItMatters":"Tirzepatide represents a paradigm shift in incretin-based therapy by targeting two hormone pathways instead of one. The dual mechanism appears to produce greater blood sugar control and weight loss than GLP-1-only drugs, while maintaining a manageable safety profile. As a 39-amino-acid peptide, it demonstrates how sophisticated peptide engineering can create therapeutics with dual receptor activity from a single molecule.","specificNumbers":"","methodology":"Narrative review summarizing the pharmacology, pharmacokinetics, pharmacodynamics, and clinical trial evidence (SURPASS program) for tirzepatide in the management of type 2 diabetes mellitus.","limitations":"As a review article, this paper does not present original data. At the time of publication (2023), tirzepatide was approved for diabetes but obesity approval was pending. The review focuses primarily on SURPASS trial data, which may not fully represent real-world effectiveness and adherence. Long-term cardiovascular outcomes and safety data beyond the trial periods were not yet available."},{"rthcId":"RPEP-07552","title":"Combined GLP-1 Receptor Agonist and Amylin Analogue Pharmacotherapy to Treat Obesity Comorbid With Type 1 Diabetes.","authors":"Wong, Gunther; Garner, Erica M; Srivastava, Gitanjali","year":2023,"journal":"JCEM case reports, 1(2), luad040","doi":"10.1210/jcemcr/luad040","pmid":"37908483","tags":["glp-1-receptor-agonists","amylin"],"studyType":"Case Report","evidenceStrength":"Low","keyFinding":"Three patients with type 1 diabetes and obesity achieved substantial weight loss using a combination of a GLP-1 receptor agonist and pramlintide (an amylin analog). Patient 1 lost 20.9 kg (16.1% of body weight) over 10 months on semaglutide plus pramlintide. Patient 2 lost a total of 21.2 kg (23.1% of body weight) after adding dulaglutide and pramlintide to her regimen. Patient 3 lost 14.6 kg (17.9% of body weight) over 6 months on semaglutide plus pramlintide. All three experienced no significant side effects, needed less insulin, and maintained or improved their HbA1c levels.","whyItMatters":"People with type 1 diabetes who also have obesity face a unique challenge: most weight loss drugs are studied in type 2 diabetes patients, leaving a significant treatment gap. This case series suggests that combining a GLP-1 drug with pramlintide may produce impressive weight loss in this underserved population without worsening blood sugar control — potentially by targeting appetite through two complementary gut-brain pathways.","specificNumbers":"","methodology":"This is a case series describing three patients seen in clinical practice. Each patient with type 1 diabetes and obesity was prescribed a GLP-1 receptor agonist (semaglutide or dulaglutide) in combination with pramlintide. Weight, HbA1c, insulin requirements, and side effects were tracked over 6 to 10 months of treatment.","limitations":"As a case series of only 3 patients, this provides the lowest level of clinical evidence. There was no control group, no randomization, and no blinding. Individual results may not be generalizable. The follow-up period was relatively short (6-10 months), so long-term efficacy and safety are unknown. One patient was also on topiramate, making it harder to attribute all weight loss to the peptide combination."},{"rthcId":"RPEP-07553","title":"Sodium glucose cotransporter 2 inhibitors and gout risk: a sequence symmetry analysis.","authors":"Wood, David T; Waterbury, Nancee V; Lund, Brian C","year":2023,"journal":"Clinical rheumatology, 42(9), 2469-2475","doi":"10.1007/s10067-023-06647-z","pmid":"37264145","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07554","title":"Purification, Identification, and Inhibitory Mechanisms of a Novel ACE Inhibitory Peptide from Torreya grandis.","authors":"Wu, Fenghua; Luo, Xiaohui; Zhang, Yongzhu; Wang, Peng; Chang, Yinzi; He, Zhiping; Liu, Xingquan","year":2023,"journal":"Nutrients, 15(10)","doi":"10.3390/nu15102374","pmid":"37242257","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07555","title":"Protamine-mediated efficient transcellular and transmucosal delivery of proteins.","authors":"Wu, Jiamin; Jones, Natalie; Fayez, Nojoud A L; Chao, Po-Han; Wu, Angeline; de Araujo, Daniele Ribeiro; Rouhollahi, Elham; Jia, Analisa; Li, Shyh-Dar","year":2023,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 356, 373-385","doi":"10.1016/j.jconrel.2023.03.002","pmid":"36878318","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07556","title":"Peptidomic analysis of the angiotensin-converting-enzyme inhibitory peptides in milk fermented with Lactobacillus delbrueckii QS306 after ultrahigh pressure treatment.","authors":"Wu, Nan; Zhang, Fengmei; Shuang, Quan","year":2023,"journal":"Food research international (Ottawa, Ont.), 164, 112406","doi":"10.1016/j.foodres.2022.112406","pmid":"36737987","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07557","title":"Screening, Characterization, and Mechanistic Evaluation of Angiotensin Converting Enzyme Inhibitory Peptides Derived from Milk Fermented with Lactobacillus delbrueckii QS306 with and without Ultrahigh-Pressure Treatment.","authors":"Wu, Nan; Wuhanqimuge; Shuang, Quan","year":2023,"journal":"Journal of agricultural and food chemistry","doi":"10.1021/acs.jafc.3c03752","pmid":"37791768","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"From milk fermented with Lactobacillus delbrueckii QS306, researchers identified 27 novel pentapeptides (five amino acids each) with potential angiotensin-converting enzyme inhibitory (ACEI) activity. Of seven tested peptides, three — HLPLP, PYPQR, and VAPFP — showed the best ACE inhibition (lowest IC50 values). However, in vitro digestion simulation significantly reduced their activity, indicating poor stability against gut enzymes.\n\nMolecular docking and dynamics simulations revealed these peptides inhibit ACE through hydrogen bonding and hydrophobic interactions at the enzyme's active site, providing a structural basis for their blood pressure-lowering potential.","whyItMatters":"High blood pressure is the leading modifiable risk factor for cardiovascular disease. ACE inhibitor drugs (like lisinopril, enalapril) are among the most prescribed medications globally. Discovering natural ACE-inhibiting peptides in fermented dairy products could lead to functional foods that help manage blood pressure through diet. The challenge — as this study reveals — is that many of these peptides are destroyed during digestion, which must be solved before they can be practical.","specificNumbers":"27 novel pentapeptides identified · 7 tested for activity · 3 top performers (HLPLP, PYPQR, VAPFP) · Significant activity loss during simulated digestion · Molecular docking confirmed ACE binding","methodology":"Milk was fermented with L. delbrueckii QS306 with and without ultrahigh-pressure treatment. Peptides were identified using UPLC-Q-Exactive-HF-X-MS/MS mass spectrometry. Bioinformatic analysis screened for ACEI potential. Selected peptides were synthesized and tested for ACE inhibition (IC50 values). Digestive stability was assessed via in vitro gastrointestinal simulation. Binding mechanisms were investigated using molecular docking and molecular dynamics simulations.","limitations":"The three best peptides showed significant activity loss during simulated digestion, questioning their practical effectiveness when consumed orally in fermented milk. All testing was in vitro — no animal or human blood pressure studies were conducted. The ultrahigh-pressure treatment's specific impact on peptide generation versus activity was incompletely characterized in the abstract. The IC50 values and specific activity numbers were not detailed in the abstract."},{"rthcId":"RPEP-07558","title":"Rational design of Abhisin-like peptides enables generation of potent antimicrobial activity against pathogens.","authors":"Wu, Peifen; Yang, Jie; Chen, Chi; Li, Ruili; Chen, Shunxian; Weng, Yanlin; Lin, Yayi; Chen, Zhiying; Yu, Fengfan; Lü, Xucong; Ni, Li; Han, Jinzhi","year":2023,"journal":"Applied microbiology and biotechnology, 107(21), 6621-6640","doi":"10.1007/s00253-023-12748-1","pmid":"37672069","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07559","title":"Use of sodium alginate coatings to improve bioavailability of liposomes containing DPP-IV inhibitory collagen peptides.","authors":"Wu, Peihan; Chen, Ling; Chen, Maoshen; Chiou, Bor-Sen; Xu, Feifei; Liu, Fei; Zhong, Fang","year":2023,"journal":"Food chemistry, 414, 135685","doi":"10.1016/j.foodchem.2023.135685","pmid":"36809726","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07560","title":"The Structure of Cyclic Neuropeptide Somatostatin and Octapeptide Octreotide in the Presence of Copper Ions: Insights from Transition Metal Ion FRET and Native Ion Mobility-Mass Spectrometry.","authors":"Wu, Ri; Benzenberg, Lukas R; Svingou, Despoina; Zenobi, Renato","year":2023,"journal":"Journal of the American Chemical Society, 145(19), 10542-10547","doi":"10.1021/jacs.2c13613","pmid":"37146120","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Using transition metal ion FRET and native ion mobility-mass spectrometry, researchers identified two Cu(II) binding sites in both somatostatin (SST) and octreotide (OCT):\n\n1. Near the disulfide bond — this site initiates self-aggregation of somatostatin, causing the peptide to clump and lose function\n2. Complexed by two aromatic residues — this site directly affects the essential motif for receptor binding, impairing SST/OCT interaction with somatostatin receptors\n\nBoth binding sites were confirmed by collision-induced dissociation experiments. The structural changes upon copper binding affected both local conformation (FRET distances) and global peptide shape (ion mobility cross-sections).","whyItMatters":"Octreotide is one of the most important peptide drugs in clinical use, treating neuroendocrine tumors, acromegaly, and other conditions. Understanding how metal ions affect its structure and receptor binding is critical for drug formulation, storage, and efficacy. In the body, copper ions are present in the nervous system and could potentially modulate somatostatin signaling in ways that affect neurological and endocrine function. This has implications for both peptide pharmacology and understanding neuropeptide biology in health and disease.","specificNumbers":"","methodology":"Transition metal ion Förster resonance energy transfer (tmFRET) was used to measure intramolecular distances in somatostatin and octreotide in the presence and absence of Cu(II). Native ion mobility-mass spectrometry (IM-MS) provided global shape information for gas-phase peptide ions. Collision-induced dissociation (CID) confirmed binding site locations. The combination of local distance constraints (tmFRET) and global shape (IM-MS) provided comprehensive structural characterization.","limitations":"The study primarily examined gas-phase peptide ions, which may not perfectly replicate solution-phase or in vivo conditions. The Cu(II) concentrations used may not reflect physiological copper levels. Functional biological assays (receptor binding, cellular responses) were not performed to quantify the impact of copper binding on actual biological activity. Only copper was studied as a metal ion — other biologically relevant metals (zinc, iron) may interact differently."},{"rthcId":"RPEP-07561","title":"The role and mechanism of the gut microbiota in the development and treatment of diabetic kidney disease.","authors":"Wu, Xiaofang; Zhao, Lei; Zhang, Yujiang; Li, Kailong; Yang, Jurong","year":2023,"journal":"Frontiers in physiology, 14, 1166685","doi":"10.3389/fphys.2023.1166685","pmid":"37153213","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07562","title":"Design and characterization of a novel tumor-homing cell-penetrating peptide for drug delivery in TGFBR3 high-expressing tumors.","authors":"Wu, Yi-Jie; Lei, Jin; Zhao, Jian; Cao, Xue-Wei; Wang, Fu-Jun","year":2023,"journal":"Chemical biology & drug design, 102(6), 1421-1434","doi":"10.1111/cbdd.14333","pmid":"37620132","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07563","title":"Recent Uses of Lipid Nanoparticles, Cell-Penetrating and Bioactive Peptides for the Development of Brain-Targeted Nanomedicines against Neurodegenerative Disorders.","authors":"Wu, Yu; Angelova, Angelina","year":2023,"journal":"Nanomaterials (Basel, Switzerland), 13(23)","doi":"10.3390/nano13233004","pmid":"38063700","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07564","title":"Acid-Responsive Macroporous Silica Nanoparticles for Bcl-2-Functional-Converting Peptide Release and Synergism with Celastrol for Enhanced Therapy against Resistant Cancer.","authors":"Wu, Yuehuang; Zhou, Min; Lin, Ruimiao; Yu, Lixue; Zhang, Xiaokun; Xie, Jingjing","year":2023,"journal":"ACS applied materials & interfaces, 15(25), 30427-30442","doi":"10.1021/acsami.3c03670","pmid":"37312263","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07565","title":"Selection of goat β-casein derived ACE-inhibitory peptide SQPK and insights into its effect and regulatory mechanism on the function of endothelial cells.","authors":"Wu, Yulong; Zhang, Jin; Mu, Tong; Zhang, Hong; Cao, Jianxin; Li, Huanhuan; Tang, Honggang; Chen, Lihong; Liu, Hongyun; Xu, Xianrong; Zhao, Ke","year":2023,"journal":"International journal of biological macromolecules, 253(Pt 6), 127312","doi":"10.1016/j.ijbiomac.2023.127312","pmid":"37827416","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07566","title":"The effect of exenatide (a GLP-1 analogue) and sitagliptin (a DPP-4 inhibitor) on asymmetric dimethylarginine (ADMA) metabolism and selected biomarkers of cardiac fibrosis in rats with fructose-induced metabolic syndrome.","authors":"Wójcicka, G; Pradiuch, A; Fornal, E; Stachniuk, A; Korolczuk, A; Marzec-Kotarska, B; Nikolaichuk, H; Czechowska, G; Kozub, A; Trzpil, A; Góralczyk, A; Bełtowski, J","year":2023,"journal":"Biochemical pharmacology, 214, 115637","doi":"10.1016/j.bcp.2023.115637","pmid":"37290595","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07567","title":"Sequences analysis and pituitary actions of tachykinins in Chinese sturgeon (Acipenser sinensis).","authors":"Xie, Yunyi; Shi, Xuetao; Xiao, Kan; Zhou, Lingling; Shu, Tingting; Du, Hejun; Yang, Jing; Hu, Guangfu","year":2023,"journal":"Gene, 879, 147592","doi":"10.1016/j.gene.2023.147592","pmid":"37356741","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07568","title":"Comparison of the efficacy and safety of 10 glucagon-like peptide-1 receptor agonists as add-on to metformin in patients with type 2 diabetes: a systematic review.","authors":"Xie, Zeyu; Hu, Jia; Gu, Hangye; Li, Mengting; Chen, Jisheng","year":2023,"journal":"Frontiers in endocrinology, 14, 1244432","doi":"10.3389/fendo.2023.1244432","pmid":"37701904","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07569","title":"Cath-DM-NT, a peptide derived from the skin of Duttaphrynus melanostictus, shows dual lectin-like and antioxidant activity.","authors":"Xiong, Weichen; Xie, Jianpeng; Liang, Yan; Chai, Jinwei; Guo, Ruiyin; Zeng, Baishuang; Wu, Jiena; Lai, Shian; Zhang, Haiyun; Huang, Xiaowen; Chen, Xin; Xu, Xueqing","year":2023,"journal":"European journal of pharmacology, 956, 175941","doi":"10.1016/j.ejphar.2023.175941","pmid":"37536626","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07570","title":"NaV1.7 Channel Blocker [Ala5, Phe6, Leu26, Arg28]GpTx-1 Attenuates CFA-induced Inflammatory Hypersensitivity in Rats via Endogenous Enkephalin Mechanism.","authors":"Xu, Biao; Zhang, Run; Zhang, Mengna; Chen, Dan; Zhang, Qinqin; Zhang, Nan; Shi, Yonghang; Hu, Xuanran; Li, Ning; Fang, Quan","year":2023,"journal":"The journal of pain, 24(5), 840-859","doi":"10.1016/j.jpain.2022.12.012","pmid":"36586660","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07571","title":"Comparison of tropomyosin released peptide and epitope mapping after in vitro digestion from fish (Larimichthys crocea), shrimp (Litopenaeus vannamei) and clam (Ruditapes philippinarum) through SWATH-MS based proteomics.","authors":"Xu, LiLi; Zhang, Xiao Mei; Wen, Yun Qi; Zhao, Jin Long; Xu, Tong Cheng; Yong, Ling; Lin, Hong; Zhang, Hong Wei; Li, Zhen Xing","year":2023,"journal":"Food chemistry, 403, 134314","doi":"10.1016/j.foodchem.2022.134314","pmid":"36179632","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07572","title":"Antimicrobial peptides for combating drug-resistant bacterial infections.","authors":"Xuan, Jiaqi; Feng, Weiguo; Wang, Jiaye; Wang, Ruichen; Zhang, Bowen; Bo, Letao; Chen, Zhe-Sheng; Yang, Hui; Sun, Leming","year":2023,"journal":"Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy, 68, 100954","doi":"10.1016/j.drup.2023.100954","pmid":"36905712","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07573","title":"Change in pharmacodynamic variables following once-weekly tirzepatide treatment versus dulaglutide in Japanese patients with type 2 diabetes (SURPASS J-mono substudy).","authors":"Yabe, Daisuke; Kawamori, Dan; Seino, Yusuke; Oura, Tomonori; Takeuchi, Masakazu","year":2023,"journal":"Diabetes, obesity & metabolism, 25(2), 398-406","doi":"10.1111/dom.14882","pmid":"36184780","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"All three doses of tirzepatide (5, 10, and 15 mg) showed statistically significant improvements in postprandial glucose, insulin, glucagon, C-peptide, and triglyceride levels compared to dulaglutide 0.75 mg after a standardized meal test at Week 32. Tirzepatide 10 mg and 15 mg also significantly reduced body weight, and all doses significantly reduced body fat mass compared to dulaglutide at Week 52.\n\nThese pharmacodynamic differences demonstrate that the dual GIP/GLP-1 agonist tirzepatide has superior metabolic normalization compared to the GLP-1-only agonist dulaglutide across multiple postprandial parameters in Japanese patients with type 2 diabetes.","whyItMatters":"This substudy provides detailed mechanistic evidence for why tirzepatide outperforms single-target GLP-1 agonists. By measuring postprandial metabolic responses and body composition, it shows that adding GIP receptor agonism to GLP-1 activity produces broader metabolic improvement — not just better blood sugar control, but also better insulin dynamics, glucagon regulation, triglyceride handling, and fat loss. This data supports the biological rationale for dual-agonist peptide drugs.","specificNumbers":"n=48 (9+11+9+19) · 52-week study · Tirzepatide 5/10/15 mg vs dulaglutide 0.75 mg · Mean age 58.6 · BMI 27.5 · Baseline HbA1c 8.22% · Significant improvements in glucose, insulin, glucagon, C-peptide, triglycerides","methodology":"Substudy of SURPASS J-mono, a 52-week, multicenter, randomized, double-blind, active-controlled Phase 3 trial in Japan. 48 patients were randomized to tirzepatide 5 mg, 10 mg, 15 mg, or dulaglutide 0.75 mg. Postprandial metabolic variables were measured via standardized meal tolerance test at Week 32 (AUC0-6h for glucose, insulin, glucagon, C-peptide, triglycerides). Body composition was measured by bioelectrical impedance analysis at Week 52.","limitations":"Very small substudy (n=48, with only 9-19 per group), limiting statistical power and generalizability. Japanese patients may have different metabolic characteristics than other populations. The dulaglutide comparator dose (0.75 mg) is the lower approved dose in Japan — comparison against higher doses or other GLP-1 agonists might yield different results. This is a substudy of a larger trial, so it was not specifically powered for the pharmacodynamic endpoints."},{"rthcId":"RPEP-07574","title":"Glucagon-like Peptide-1 Receptor-based Therapeutics for Metabolic Liver Disease.","authors":"Yabut, Julian M; Drucker, Daniel J","year":2023,"journal":"Endocrine reviews, 44(1), 14-32","doi":"10.1210/endrev/bnac018","pmid":"35907261","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07575","title":"Advancement and application of novel cell-penetrating peptide in cancer management.","authors":"Yadav, Shikha; Singh, Pratichi","year":2023,"journal":"3 Biotech, 13(7), 234","doi":"10.1007/s13205-023-03649-1","pmid":"37323859","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Cell-penetrating peptides (CPPs) have emerged as a versatile drug delivery platform capable of transporting nucleic acids, large proteins, and chemical compounds across cell membranes with low toxicity compared to conventional carriers. The review highlights that combining CPPs with nanoparticles significantly enhances intracellular DNA delivery, and that chemical modifications to CPP structures can improve their cellular uptake efficiency.\n\nWhile CPPs have demonstrated high efficacy in cellular studies, their translation to in vivo applications remains an active area of research, with long-term side effects and potential toxicity limiting broader clinical implementation.","whyItMatters":"Cell-penetrating peptides represent a promising frontier in targeted drug delivery, particularly for cancer treatment. Their ability to ferry therapeutic cargo directly into cells — with lower toxicity than many conventional delivery systems — could make cancer therapies more effective and less harmful to patients. The ongoing development of chemical modifications and nanoparticle conjugation strategies is steadily bringing CPP-based therapies closer to clinical reality.","specificNumbers":"","methodology":"This is a narrative review article that synthesizes findings from published research on cell-penetrating peptides. The authors surveyed the literature on CPP discovery, classification, chemical modifications, membrane-crossing mechanisms, and biological applications, with a focus on cancer management.","limitations":"As a review article, this paper does not present original experimental data. The findings are dependent on the quality and scope of the studies surveyed. The review does not provide a systematic or quantitative meta-analysis, and the selection criteria for included studies are not explicitly described."},{"rthcId":"RPEP-07576","title":"Performance of Cell-Penetrating Peptides Anchored to Polysaccharide Platforms Applied via Various Mucosal Routes as an Absorption Enhancer.","authors":"Yagi, Haruya; Tomono, Takumi; Handa, Yuma; Saito, Natsuki; Ukawa, Masami; Miyata, Kohei; Shigeno, Koichi; Sakuma, Shinji","year":2023,"journal":"Molecular pharmaceutics, 20(1), 303-313","doi":"10.1021/acs.molpharmaceut.2c00657","pmid":"36484773","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07577","title":"Feasibility of Exenatide, a GLP-1R Agonist, for Treating Cocaine Use Disorder: A Case Series Study.","authors":"Yammine, Luba; Balderas, Jessica C; Weaver, Michael F; Schmitz, Joy M","year":2023,"journal":"Journal of addiction medicine, 17(4), 481-484","doi":"10.1097/ADM.0000000000001147","pmid":"37579116","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07578","title":"Glucagon-Like Peptide 1 Receptor Agonists Versus Sodium-Glucose Cotransporter 2 Inhibitors for Atherosclerotic Cardiovascular Disease in Patients With Type 2 Diabetes.","authors":"Yanai, Hidekatsu; Adachi, Hiroki; Hakoshima, Mariko; Katsuyama, Hisayuki","year":2023,"journal":"Cardiology research, 14(1), 12-21","doi":"10.14740/cr1459","pmid":"36896226","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07579","title":"Endogenous Inflammatory Mediators Produced by Injury Activate TRPV1 and TRPA1 Nociceptors to Induce Sexually Dimorphic Cold Pain That Is Dependent on TRPM8 and GFRα3.","authors":"Yang, Chenyu; Yamaki, Shanni; Jung, Tyler; Kim, Brian; Huyhn, Ryan; McKemy, David D","year":2023,"journal":"The Journal of neuroscience : the official journal of the Society for Neuroscience, 43(15), 2803-2814","doi":"10.1523/JNEUROSCI.2303-22.2023","pmid":"36898840","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07580","title":"Endogenous inflammatory mediators produced by injury activate TRPV1 and TRPA1 nociceptors to induce sexually dimorphic cold pain that is dependent on TRPM8 and GFRα3.","authors":"Yang, Chenyu; Yamaki, Shanni; Jung, Tyler; Kim, Brian; Huyhn, Ryan; McKemy, David D","year":2023,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2023.01.23.525238","pmid":"36747719","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07581","title":"Hypothalamic neuroendocrine integration of reproduction and metabolism in mammals.","authors":"Yang, Fan; Zhao, Shuang; Wang, Pingqing; Xiang, Wei","year":2023,"journal":"The Journal of endocrinology, 258(3)","doi":"10.1530/JOE-23-0079","pmid":"37561042","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07582","title":"Rational Design and Antimicrobial Potency Assessment of Abaecin Analogues.","authors":"Yang, Jie; Wu, Peifen; Weng, Yanlin; Lin, Yayi; Chen, Zhiying; Yu, Fengfan; Lv, Xucong; Ni, Li; Han, Jinzhi","year":2023,"journal":"ACS biomaterials science & engineering, 9(12), 6698-6714","doi":"10.1021/acsbiomaterials.3c01234","pmid":"37988627","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07583","title":"Bionic peptide scaffold in situ polarization and recruitment of M2 macrophages to promote peripheral nerve regeneration.","authors":"Yang, Pengxiang; Peng, Yong; Dai, Xiu; Jie, Jing; Kong, Deling; Gu, Xiaosong; Yang, Yumin","year":2023,"journal":"Bioactive materials, 30, 85-97","doi":"10.1016/j.bioactmat.2023.07.003","pmid":"37575879","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07584","title":"Neoantigen vaccination augments antitumor effects of anti-PD-1 on mouse hepatocellular carcinoma.","authors":"Yang, Shih-Feng; Weng, Meng-Tzu; Liang, Ja-Der; Chiou, Ling-Ling; Hsu, Yu-Chen; Lee, Ying-Te; Liu, Shin-Yun; Wu, Meng-Chuan; Chou, Huei-Chi; Wang, Li-Fang; Yu, Shu-Han; Lee, Hsuan-Shu; Sheu, Jin-Chuan","year":2023,"journal":"Cancer letters, 563, 216192","doi":"10.1016/j.canlet.2023.216192","pmid":"37088327","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07585","title":"Short Peptide Nanofiber Biomaterials Ameliorate Local Hemostatic Capacity of Surgical Materials and Intraoperative Hemostatic Applications in Clinics.","authors":"Yang, Zehong; Chen, Lihong; Liu, Ji; Zhuang, Hua; Lin, Wei; Li, Changlong; Zhao, Xiaojun","year":2023,"journal":"Advanced materials (Deerfield Beach, Fla.), 35(39), e2301849","doi":"10.1002/adma.202301849","pmid":"36942893","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07586","title":"A Designed Analog of an Antimicrobial Peptide, Crabrolin, Exhibits Enhanced Anti-Proliferative and In Vivo Antimicrobial Activity.","authors":"Yao, Aifang; Ma, Yingxue; Sun, Ruize; Zou, Wanchen; Chen, Xiaoling; Zhou, Mei; Ma, Chengbang; Chen, Tianbao; Shaw, Chris; Wang, Lei","year":2023,"journal":"International journal of molecular sciences, 24(19)","doi":"10.3390/ijms241914472","pmid":"37833918","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07587","title":"Influence of recombinant human B-type natriuretic peptide on improving ventricular function in patients with ST elevation myocardial infarction.","authors":"Yao, L; Liu, C-J; Zhang, L; Lin, Y; Hu, Y-M","year":2023,"journal":"European review for medical and pharmacological sciences, 27(8), 3420-3429","doi":"10.26355/eurrev_202304_32112","pmid":"37140291","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07588","title":"Self-assembling peptide RADA16: a promising scaffold for tissue engineering and regenerative medicine.","authors":"Yao, Xin; Hu, Yicun; Lin, Maoqiang; Peng, Kaichen; Wang, Peng; Gao, Yanbing; Gao, Xidan; Guo, Taowen; Zhang, Xiaobo; Zhou, Haiyu","year":2023,"journal":"Nanomedicine (London, England)","doi":"10.2217/nnm-2023-0161","pmid":"37750388","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07589","title":"Cortexin® Ameliorates High Glucose-Induced Neuropathy in Cultured Rat Sensory Neurons.","authors":"Yazar, Uğur; Ayar, Ahmet","year":2023,"journal":"Neuroendocrinology, 113(9), 924-929","doi":"10.1159/000530766","pmid":"37080184","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07590","title":"Machine Learning Advances in Predicting Peptide/Protein-Protein Interactions Based on Sequence Information for Lead Peptides Discovery.","authors":"Ye, Jiahao; Li, An; Zheng, Hao; Yang, Banghua; Lu, Yiming","year":2023,"journal":"Advanced biology, 7(6), e2200232","doi":"10.1002/adbi.202200232","pmid":"36775876","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07591","title":"Targeting the Nerve-Cancer Circuit.","authors":"Ye, Yi; Xie, Tongxin; Amit, Moran","year":2023,"journal":"Cancer research, 83(15), 2445-2447","doi":"10.1158/0008-5472.CAN-23-1754","pmid":"37470842","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Research by Restaino and colleagues demonstrated that tumors across different types, origins, and anatomic locations are densely innervated predominantly by TRPV1+ sensory nerve fibers with likely functional connectivity contributing to increased electrical activity in the tumor bed. The neuropeptide substance P produced by these intratumoral fibers stimulates the neurokinin 1 receptor (NK1R) on tumor cells, driving proliferation and migration. This represents a potentially generalizable molecular pathway mediating cancer-nerve interaction across tumor types.","whyItMatters":"If substance P/NK1R signaling is a universal cancer growth mechanism, NK1R antagonists (some already approved for other uses like anti-nausea) could become broadly applicable cancer treatments. This reframes tumors not just as masses of abnormal cells but as organs with active nerve connections that drive their growth — opening an entirely new therapeutic front.","specificNumbers":"","methodology":"This is a commentary/perspective article discussing findings from the Restaino et al. study on nerve-tumor interactions. The underlying research used anatomical and functional characterization of tumor innervation across multiple cancer types, with molecular dissection of the substance P/NK1R signaling axis.","limitations":"This is a commentary article, not original research, so it discusses findings from a single referenced study. While the concept of universal tumor innervation is compelling, the degree to which substance P/NK1R signaling drives growth may vary across cancer types and stages. Clinical validation of NK1R antagonists as anti-cancer agents is still needed."},{"rthcId":"RPEP-07592","title":"Prognostic value of Growth differentiation factors 15 in Acute heart failure patients with preserved ejection fraction.","authors":"Yin, Dan; Yan, Xiaofang; Bai, Xueke; Tian, Aoxi; Gao, Yan; Li, Jing","year":2023,"journal":"ESC heart failure, 10(2), 1025-1034","doi":"10.1002/ehf2.14271","pmid":"36519216","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07593","title":"Development and validation of a hybrid immunoaffinity LC-MS/MS assay for quantitation of total antibody (TAb) from an antibody drug conjugate (ADC) PYX-201 in human plasma.","authors":"Yin, Feng; Adhikari, Diana; Peay, Marlking; Cortes, Diego; Garada, Mohammed; Shane Woolf, M; Ma, Eric; Lebarbenchon, Diane; Mylott, William; Dyszel, Mike; Harriman, Shawn; Pinkas, Jan","year":2023,"journal":"Journal of chromatography. B, Analytical technologies in the biomedical and life sciences, 1228, 123844","doi":"10.1016/j.jchromb.2023.123844","pmid":"37579604","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07594","title":"Thymosin β4 and Actin: Binding Modes, Biological Functions and Clinical Applications.","authors":"Ying, Yuyuan; Lin, Chen; Tao, Nana; Hoffman, Robert D; Shi, Dongling; Chen, Zhijin; Gao, Jianli","year":2023,"journal":"Current protein & peptide science, 24(1), 78-88","doi":"10.2174/1389203724666221201093500","pmid":"36464872","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07595","title":"Ameliorative effect of mussel-derived ACE inhibitory peptides on spontaneous hypertension rats.","authors":"You, Qiaoni; Sun, Xiaopeng; Chen, Jinli; Yu, Jia; Wei, Yuxi","year":2023,"journal":"European journal of nutrition, 62(7), 3097-3111","doi":"10.1007/s00394-023-03222-9","pmid":"37505286","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07596","title":"Tailored Apoptotic Vesicle Delivery Platform for Inflammatory Regulation and Tissue Repair to Ameliorate Ischemic Stroke.","authors":"You, Yang; Xu, Jianpei; Liu, Yipu; Li, Haichun; Xie, Laozhi; Ma, Chuchu; Sun, Yinzhe; Tong, Shiqiang; Liang, Kaifan; Zhou, Songlei; Ma, Fenfen; Song, Qingxiang; Xiao, Wenze; Fu, Kaikai; Dai, Chengxiang; Li, Suke; Lei, Jigang; Mei, Qiyong; Gao, Xiaoling; Chen, Jun","year":2023,"journal":"ACS nano, 17(9), 8646-8662","doi":"10.1021/acsnano.3c01497","pmid":"37099675","tags":["cell-penetrating-peptides","stroke"],"studyType":"animal-and-cell","evidenceStrength":"preliminary","keyFinding":"Researchers engineered a targeted drug delivery system for ischemic stroke by combining three innovations: (1) using α-mangostin to simultaneously induce mesenchymal stem cell apoptosis and serve as an anti-inflammatory cargo, (2) harvesting the resulting apoptotic vesicles (ApoVs) loaded with both α-mangostin and beneficial protein payloads, and (3) decorating the vesicles with MAP, a matrix metalloproteinase-activatable cell-penetrating peptide that responds to the stroke injury microenvironment.\n\nThe MAP-functionalized vesicles targeted the injured ischemic brain after systemic injection and provided enhanced neuroprotection through synergistic effects of the vesicles and α-mangostin. The ApoV protein payloads regulated immune responses, promoted blood vessel formation, and stimulated cell growth — all contributing to brain repair after stroke.","whyItMatters":"Ischemic stroke is a leading cause of death and disability with very limited treatment options beyond the narrow time window for clot-busting drugs. Stem cell-derived apoptotic vesicles have natural anti-inflammatory and tissue repair properties, but they lack targeting ability and haven't been developed as drug delivery platforms. This study solves both problems by loading them with a therapeutic agent and adding a 'smart' peptide that only activates at the stroke site. The approach could become a framework for treating not just stroke but other inflammatory brain injuries.","specificNumbers":"MAP peptide: microenvironment-responsive targeting · α-mangostin: dual-purpose (apoptosis inducer + anti-inflammatory cargo) · MSC-derived apoptotic vesicles · systemic injection → brain targeting · synergistic neuroprotection · protein payloads regulate immunity, angiogenesis, proliferation","methodology":"Mesenchymal stem cells were treated with α-mangostin to induce apoptosis, generating apoptotic vesicles pre-loaded with the compound. The vesicle surface was functionalized with MAP (matrix metalloproteinase-activatable cell-penetrating peptide), which remains inactive in normal tissue but activates in the inflammatory stroke microenvironment where matrix metalloproteinases are elevated. The engineered vesicles were injected systemically in stroke animal models and assessed for brain targeting, neuroprotection, and therapeutic outcomes. Proteomic analysis characterized the internal protein payloads.","limitations":"This is a preclinical study; no human data exists. The complexity of the multi-component system (stem cell culture, apoptosis induction, drug loading, peptide modification) presents significant manufacturing and quality control challenges for clinical translation. Long-term safety of systemically injected engineered apoptotic vesicles is unknown. The stroke model may not capture the full complexity of human ischemic stroke, particularly regarding timing and comorbidities."},{"rthcId":"RPEP-07597","title":"Effect of the Dual Glucose‐Dependent Insulinotropic Peptide/Gulcagon‐like Peptide 1 Receptor Agonist Tirzepatide on Lipid Profile and Waist Circumference: A Systematic Review and Meta‐analysis.","authors":"Yu, Dan; Shen, Shanshan; Zhang, Jinghong; Wang, Qijun","year":2023,"journal":"Clinical therapeutics, 45(8), 787-796","doi":"10.1016/j.clinthera.2023.06.008","pmid":"37455226","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07598","title":"The relationship between the use of GLP-1 receptor agonists and the incidence of respiratory illness: a meta-analysis of randomized controlled trials.","authors":"Yu, Meixin; Wang, Ruxin; Pei, Ling; Zhang, Xiaofang; Wei, Jinjing; Wen, Yun; Liu, Han; Ye, Haowen; Wang, Jinghao; Wang, Lihong","year":2023,"journal":"Diabetology & metabolic syndrome, 15(1), 164","doi":"10.1186/s13098-023-01118-6","pmid":"37491292","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07599","title":"Disulfide Click Reaction for Stapling of S-terminal Peptides.","authors":"Yu, Qing; Bai, Leiyang; Jiang, Xuefeng","year":2023,"journal":"Angewandte Chemie (International ed. in English), 62(52), e202314379","doi":"10.1002/anie.202314379","pmid":"37950389","tags":[],"studyType":"in vitro","evidenceStrength":"very low","keyFinding":"Researchers developed a \"disulfide click\" stapling method that converts linear peptides into stable macrocyclic (ring-shaped) forms with improved metabolic stability and ability to enter cells. Using a library of 17 stapling reagents with adjustable lengths and angles, they could bridge peptides from 3 to 18 amino acids long, creating ring structures of 18 to 48 atoms under gentle, biocompatible conditions. The stapled peptides gained anti-cancer activity against HCT-116 colorectal cancer cells (IC50 = 6.81 μM) while the unstapled linear versions had no biological activity. A unique feature: the disulfide staple can be chemically reversed inside cells, releasing the native peptide for intracellular delivery.","whyItMatters":"Most therapeutic peptides fail because they are quickly degraded by enzymes and cannot cross cell membranes. Stapling — chemically locking peptides into a ring shape — addresses both problems, but existing methods often use harsh chemistry or irreversible crosslinks. This disulfide click approach is notable because it works under mild conditions, offers a large toolbox of linker geometries, and is reversible — the staple breaks down inside cells to release the active peptide. This \"staple, enter, release\" strategy is a clever solution to the peptide drug delivery problem.","specificNumbers":"17 stapling reagents · Peptides 3-18 amino acids · 18-48 membered macrocycles · IC50 = 6.81 μM (HCT-116 cells) · Biocompatible conditions","methodology":"The researchers designed and synthesized 17 disulfide-based stapling reagents with varying lengths and angles. These were reacted with sulfur-containing (S-terminal) peptides via double or triple click reactions to produce macrocyclic peptides under biocompatible conditions. The stapled peptides were characterized for helical conformation, metabolic stability, and cellular permeability. Anticancer activity was tested against HCT-116 colorectal cancer cells. Reversibility was demonstrated using the reducing agent TCEP to release native peptides from the stapled forms.","limitations":"This is primarily a chemistry methodology paper with limited biological validation — only one cancer cell line was tested. The IC50 of 6.81 μM, while demonstrating activity, is relatively modest for a drug candidate. No in vivo studies, pharmacokinetic data, or selectivity against normal cells were reported. The requirement for sulfur-containing terminal residues may limit which peptides can be stapled with this method. The intracellular release mechanism (disulfide reduction) assumes a reducing intracellular environment, which may vary across cell types and disease states."},{"rthcId":"RPEP-07600","title":"Exogenous Thymosin Beta 4 Suppresses IPF-Lung Cancer in Mice: Possibly Associated with Its Inhibitory Effect on the JAK2/STAT3 Signaling Pathway.","authors":"Yu, Rui; Gao, Dandi; Bao, Jiali; Sun, Ronghao; Cui, Mengqi; Mao, Yunyun; Li, Kai; Hu, Enbo; Zhai, Yanfang; Liu, Yanhong; Gao, Yuemei; Xiao, Ting; Zhou, Honggang; Yang, Cheng; Xu, Junjie","year":2023,"journal":"International journal of molecular sciences, 24(4)","doi":"10.3390/ijms24043818","pmid":"36835236","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07601","title":"Therapeutic potential of tolerance-based peptide vaccines in autoimmune diseases.","authors":"Yu, Xueting; Mai, Yaping; Wei, Yaya; Yu, Na; Gao, Ting; Yang, Jianhong","year":2023,"journal":"International immunopharmacology, 116, 109740","doi":"10.1016/j.intimp.2023.109740","pmid":"36696858","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07602","title":"Effectiveness and cost-effectiveness of six GLP-1RAs for treatment of Chinese type 2 diabetes mellitus patients that inadequately controlled on metformin: a micro-simulation model.","authors":"Yuan, Shuai; Wu, Yingyu","year":2023,"journal":"Frontiers in public health, 11, 1201818","doi":"10.3389/fpubh.2023.1201818","pmid":"37744474","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07603","title":"Comparing the effectiveness of long-term use of daily and weekly glucagon-like peptide-1 receptor agonists treatments in patients with nonalcoholic fatty liver disease and type 2 diabetes mellitus: a network meta-analysis.","authors":"Yuan, Xia; Gao, Zhe; Yang, Caixuan; Duan, Kaixin; Ren, Luping; Song, Guangyao","year":2023,"journal":"Frontiers in endocrinology, 14, 1170881","doi":"10.3389/fendo.2023.1170881","pmid":"37342259","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07604","title":"Discovery of a potent and long-acting Xenopus GLP-1-based GLP-1/glucagon/Y2 receptor triple agonist.","authors":"Yuan, Yongliang; Yan, Zhiming; Lao, Qifang; Jiang, Neng; Wu, Shuangmin; Lu, Qinpei; Han, Jing; Zhao, Songfeng","year":2023,"journal":"European journal of medicinal chemistry, 247, 115036","doi":"10.1016/j.ejmech.2022.115036","pmid":"36571995","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07605","title":"Screening potential hypertensive peptides using two consecutive bioassay-guided SPE fractionations and identification of an ACE inhibitory peptide, DHSTAVW (DW7), derived from pearl garlic protein hydrolysate.","authors":"Yudho Sutopo, Christoper Caesar; Aznam, Nurfina; Arianingrum, Retno; Hsu, Jue-Liang","year":2023,"journal":"Peptides, 167, 171046","doi":"10.1016/j.peptides.2023.171046","pmid":"37330111","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07606","title":"Targeting Melanocortin Receptors Using SNAr-Type Macrocyclization: A Doubly Orthogonal Route to Cyclic Peptide Conjugates.","authors":"Yue, Wenxiao K; Zhang, Tianxia; Shandre Mugan, Rekha; Barlow, Nicholas; Chalmers, David K; Pouton, Colin W; Thompson, Philip E","year":2023,"journal":"Journal of medicinal chemistry, 66(5), 3273-3283","doi":"10.1021/acs.jmedchem.2c01587","pmid":"36808973","tags":[],"studyType":"Medicinal Chemistry / Drug Design","evidenceStrength":"preliminary","keyFinding":"Researchers developed a new and efficient method for creating cyclic peptides — ring-shaped peptide molecules that are generally more stable and drug-like than their linear counterparts. Using nucleophilic aromatic substitution (SNAr), they created thioether macrocycles that can be built in solution on unprotected peptides or on resin-bound peptides with side-chain protection in place.\n\nThe method's key advantage is that it is \"doubly orthogonal\" — the chemical reactions used for cyclization don't interfere with standard peptide synthesis chemistry, and the resulting products contain electron-withdrawing groups that can be used for further modifications like adding labels or drug conjugates. Applied to melanocortin receptor targets, the approach generated a library of potent melanocortin agonists with distinct subtype selectivity — meaning different cyclic peptides could preferentially activate specific melanocortin receptor subtypes.","whyItMatters":"Melanocortin receptors control critical functions including appetite, sexual function, skin pigmentation, and inflammation. Drugs like bremelanotide (Vyleesi) and setmelanotide already target this system. But creating selective melanocortin agonists — ones that activate specific receptor subtypes without triggering unwanted effects — has been a major challenge. This new cyclization method allows rapid generation of diverse cyclic peptide libraries, accelerating the discovery of more selective and potent melanocortin drugs.","specificNumbers":"SNAr macrocyclization method · Thioether-linked cyclic peptides · Library of potent melanocortin agonists generated · Distinct subtype selectivity achieved · Published in J. Med. Chem.","methodology":"The researchers developed and validated a macrocyclization method using nucleophilic aromatic substitution (SNAr) to form thioether bridges in peptides. They tested the approach both in solution with unprotected peptidomimetics and on solid-phase resin with protected peptides. The resulting cyclic peptides were evaluated for binding and activation at melanocortin receptors, generating a library with varying subtype selectivity profiles.","limitations":"This is a chemistry/drug design study — no animal or human testing. The potency and selectivity were assessed in receptor binding assays only, not in vivo. Whether these cyclic peptides would be bioavailable, stable in the body, or therapeutically useful requires further preclinical and clinical testing. The library approach generates many candidates but doesn't guarantee any will become drugs."},{"rthcId":"RPEP-07607","title":"Conjugation of amiodarone to a novel cardiomyocyte cell penetrating peptide for potential targeted delivery to the heart.","authors":"Yurko, Ray; Islam, Kazi; Weber, Beth; Salama, Guy; Zahid, Maliha","year":2023,"journal":"Frontiers in chemistry, 11, 1220573","doi":"10.3389/fchem.2023.1220573","pmid":"37547910","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07608","title":"Improving the efficacy of peptide vaccines in cancer immunotherapy.","authors":"Zahedipour, Fatemeh; Jamialahmadi, Khadijeh; Zamani, Parvin; Reza Jaafari, Mahmoud","year":2023,"journal":"International immunopharmacology, 123, 110721","doi":"10.1016/j.intimp.2023.110721","pmid":"37543011","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07609","title":"A Comparative Analysis of Fibroblast Activation Protein-Targeted Small Molecule-Drug, Antibody-Drug, and Peptide-Drug Conjugates.","authors":"Zana, Aureliano; Puig-Moreno, Claudia; Bocci, Matilde; Gilardoni, Ettore; Di Nitto, Cesare; Principi, Lucrezia; Ravazza, Domenico; Rotta, Giulia; Prodi, Eleonora; De Luca, Roberto; Neri, Dario; Cazzamalli, Samuele","year":2023,"journal":"Bioconjugate chemistry, 34(7), 1205-1211","doi":"10.1021/acs.bioconjchem.3c00244","pmid":"37399501","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07610","title":"Case Report: Targeting of individual somatic tumor mutations by multipeptide vaccination tailored for HLA class I and II presentation induces strong CD4 and CD8 T-cell responses in a patient with metastatic castration sensitive prostate cancer.","authors":"Zelba, Henning; Rabsteyn, Armin; Bartsch, Oliver; Kyzirakos, Christina; Kayser, Simone; Seibold, Marcel; Harter, Johannes; Latzer, Pauline; Hadaschik, Dirk; Battke, Florian; Golf, Alexander; Rettig, Matthew B; Biskup, Saskia","year":2023,"journal":"Frontiers in immunology, 14, 1271449","doi":"10.3389/fimmu.2023.1271449","pmid":"37920460","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A patient with metastatic castration-sensitive prostate cancer received two sequential personalized peptide vaccines over 33 months. The first vaccine, containing only HLA class I binding peptides, induced just one CD4+ T-cell response after 21 vaccinations. The second vaccine, incorporating both HLA class I and class II binding peptides, triggered multiple strong and durable CD4+ and CD8+ T-cell responses after only 6 vaccinations. The immune responses were polyfunctional (producing IFNγ, TNF-α, IL-2, and CD154). The patient's PSA remained undetectable for 51 months.","whyItMatters":"Metastatic prostate cancer has limited treatment options and a poor 5-year survival rate. This case demonstrates that personalized peptide vaccines targeting tumor-specific mutations can generate robust anti-tumor immune responses, and that including both HLA class I and II peptides dramatically improves vaccine efficacy — a critical design insight for future cancer vaccine trials.","specificNumbers":"33 months of vaccination · 1st vaccine: 1 response after 21 doses · 2nd vaccine: multiple responses after 6 doses · PSA undetectable for 51 months · 4 T-cell markers measured","methodology":"Case report of a single patient with metastatic castration-sensitive prostate cancer in remission. Somatic tumor mutations were identified via genomic analysis. The patient received two sequential peptide vaccines: first with HLA class I peptides only, then with both HLA class I and II peptides. Vaccine-induced T-cell responses were measured using intracellular cytokine staining after 12-day in vitro expansion, assessing four activation markers (IFNγ, TNF-α, IL-2, CD154).","limitations":"This is a single-patient case report, so the results cannot be generalized. It is impossible to determine whether the sustained PSA suppression was due to the vaccine, other treatments, or the natural disease course. The in vitro expansion period before immune monitoring may amplify responses beyond what occurs naturally in the patient."},{"rthcId":"RPEP-07611","title":"Heme and Cu2+-induced vasoactive intestinal peptide (VIP) tyrosine nitration: A possible molecular mechanism for the attenuated anti-inflammatory effect of VIP in inflammatory diseases.","authors":"Zeng, Lizhen; Zhang, Xuan; Xia, Mengyang; Ye, Huixian; Li, Hailing; Gao, Zhonghong","year":2023,"journal":"Biochimie, 214(Pt B), 176-187","doi":"10.1016/j.biochi.2023.07.011","pmid":"37481062","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07612","title":"Safety issues of tirzepatide (pancreatitis and gallbladder or biliary disease) in type 2 diabetes and obesity: a systematic review and meta-analysis.","authors":"Zeng, Qingyue; Xu, Jiao; Mu, Xingyu; Shi, Yi; Fan, Hong; Li, Shuangqing","year":2023,"journal":"Frontiers in endocrinology, 14, 1214334","doi":"10.3389/fendo.2023.1214334","pmid":"37908750","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 9 RCTs with 9,871 participants (6,828 tirzepatide, 3,043 controls), tirzepatide was not associated with a significantly increased risk of pancreatitis (RR 1.46, 95% CI 0.59–3.61, I² = 0.0%).\n\nHowever, the composite of gallbladder or biliary disease was significantly elevated with tirzepatide compared to placebo or basal insulin (RR 1.97, 95% CI 1.14–3.42, I² = 0.0%). When broken down individually, the risks of cholelithiasis (gallstones), cholecystitis (gallbladder inflammation), and biliary diseases were not individually significant.","whyItMatters":"As tirzepatide becomes one of the most prescribed medications for diabetes and obesity worldwide, understanding its safety profile is essential. Rapid weight loss from any cause can increase gallbladder disease risk, and GLP-1-class drugs have previously raised concerns about pancreatitis. This meta-analysis provides reassurance on the pancreatitis front but raises a clinically important flag about gallbladder and biliary complications that clinicians and patients should be aware of.","specificNumbers":"","methodology":"This was a systematic review and meta-analysis following PROSPERO registration (CRD42023412400). Researchers searched Embase, PubMed, and the Cochrane Library through March 2023 for randomized controlled trials comparing tirzepatide to placebo or active comparators (basal insulin, GLP-1 agonists) in people with type 2 diabetes or obesity. Heterogeneity was assessed using I² and Cochran's Q test. A fixed effects model was used to estimate safety outcomes including pancreatitis, composite gallbladder/biliary disease, cholecystitis, and cholelithiasis.","limitations":"The relatively small number of pancreatitis events across trials means the study may be underpowered to detect a true increase in risk (wide confidence interval: 0.59–3.61). The composite gallbladder/biliary outcome was significant but individual components were not, suggesting the signal may be driven by the aggregation. The search only included trials through March 2023, missing more recent large-scale studies. Fixed effects models were used, which may not be appropriate if there is undetected heterogeneity. The control groups varied (placebo, insulin, GLP-1 agonists), introducing potential comparison inconsistencies."},{"rthcId":"RPEP-07613","title":"Prediction and identification of HLA-A*0201-restricted epitopes from cancer testis antigen CT23.","authors":"Zeng, Xia; Nong, Wei-Xia; Zou, Xiao-Qiong; Li, Feng; Ge, Ying-Ying; Zhang, Qing-Mei; Luo, Bin; Huang, Wei; Zou, Jian-Xia; Fan, Rong; Xie, Xiao-Xun","year":2023,"journal":"Human vaccines & immunotherapeutics, 19(3), 2293299","doi":"10.1080/21645515.2023.2293299","pmid":"38100550","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07614","title":"Antioxioxidant and antiapoptotic effects of Thymosin β4 in Aβ-induced SH-SY5Y cells via the 5-HTR1A/ERK axis.","authors":"Zhang, Gui-Hong; Chin, Kai Ling; Yan, Shi-Yan; Pare, Rahmawati","year":2023,"journal":"PloS one, 18(10), e0287817","doi":"10.1371/journal.pone.0287817","pmid":"37788276","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07615","title":"The Antimicrobial, Hemostatic, and Anti-Adhesion Effects of a Peptide Hydrogel Constructed by the All-d-Enantiomer of Antimicrobial Peptide Jelleine-1.","authors":"Zhang, Hanru; Wu, Zhiyu; Zhou, Jingjing; Wang, Zhaopeng; Yang, Changyan; Wang, Panpan; Fareed, Muhammad Subaan; He, Yuhang; Su, Jie; Cha, Ruitao; Wang, Kairong","year":2023,"journal":"Advanced healthcare materials, 12(29), e2301612","doi":"10.1002/adhm.202301612","pmid":"37552211","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07616","title":"Impact of casein-to-whey protein ratio on gastric emptying, proteolysis, and peptidome profile of fermented milk during in vitro dynamic gastrointestinal digestion in preschool children.","authors":"Zhang, Hongyan; Duan, Sufang; Yu, Yang; Wu, Ren'an; Wang, Jingjing; Chen, Xiao Dong; Szeto, Ignatius Man-Yau; Wu, Peng; Jin, Yan","year":2023,"journal":"Food chemistry, 405(Pt B), 134840","doi":"10.1016/j.foodchem.2022.134840","pmid":"36403474","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07617","title":"Recent Advances of Cell-Penetrating Peptides and Their Application as Vectors for Delivery of Peptide and Protein-Based Cargo Molecules.","authors":"Zhang, Huifeng; Zhang, Yanfei; Zhang, Chuang; Yu, Huan; Ma, Yinghui; Li, Zhengqiang; Shi, Nianqiu","year":2023,"journal":"Pharmaceutics, 15(8)","doi":"10.3390/pharmaceutics15082093","pmid":"37631307","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review covers three generations of CPP development:\n\n1. Natural CPPs: Originally discovered in venoms from snakes, bees, and spiders, these peptides evolved to penetrate cell membranes as part of their toxic function but can be repurposed for drug delivery.\n\n2. Synthetic CPPs: Modern engineering has produced several improved designs:\n   • Cyclic CPPs with enhanced stability and membrane penetration\n   • Glycosylated CPPs with improved targeting and reduced toxicity\n   • D-form CPPs using mirror-image amino acids for protease resistance\n\n3. Therapeutic applications: Various CPPs have been used as vehicles to deliver peptide and protein drugs to cells in preclinical models of diverse diseases, with superior safety and efficiency compared to traditional delivery methods.","whyItMatters":"The biopharmaceutical industry increasingly relies on peptide and protein drugs, but their inability to cross cell membranes is a fundamental limitation. CPPs offer a solution that could unlock the therapeutic potential of biologics for intracellular targets — expanding the drug target landscape from cell-surface proteins to the entire proteome inside the cell.","specificNumbers":"","methodology":"Narrative review synthesizing literature on CPP discovery, design innovations, and therapeutic applications. Covers the evolution from natural venom-derived CPPs through synthetic engineering approaches and their preclinical applications for peptide/protein drug delivery.","limitations":"As a review, this paper does not present new experimental data. Most CPP applications discussed are preclinical. Clinical translation challenges (immunogenicity, off-target cell penetration, manufacturing scalability) are common across the field but may not be fully addressed. The review does not systematically compare CPP performance across different cargo types or disease models. Toxicity concerns with venom-derived CPPs at therapeutic doses need careful evaluation."},{"rthcId":"RPEP-07618","title":"ACE inhibitory activity and salt-reduction properties of umami peptides from chicken soup.","authors":"Zhang, Jincheng; Liang, Li; Zhang, Lili; Zhou, Xuewei; Sun, Baoguo; Zhang, Yuyu","year":2023,"journal":"Food chemistry, 425, 136480","doi":"10.1016/j.foodchem.2023.136480","pmid":"37276669","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07619","title":"Antihypertensive Effect, ACE Inhibitory Activity, and Stability of Umami Peptides from Yeast Extract.","authors":"Zhang, Jincheng; Liang, Li; Shan, Yimeng; Zhou, Xuewei; Sun, Baoguo; Liu, Yuan; Zhang, Yuyu","year":2023,"journal":"Journal of agricultural and food chemistry","doi":"10.1021/acs.jafc.3c04819","pmid":"37812565","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07620","title":"Effects of Neuropeptides on Dendritic Cells in the Pathogenesis of Psoriasis.","authors":"Zhang, Jingya; Zhao, Siqi; Xing, Xinzhu; Shang, Lin; Cao, Jiali; He, Yanling","year":2023,"journal":"Journal of inflammation research, 16, 35-43","doi":"10.2147/JIR.S397079","pmid":"36636251","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07621","title":"Oil palm kernel globulin antihypertensive peptides: isolation and characterization, ACE inhibition mechanisms, zinc-chelating activity, security and stability.","authors":"Zhang, Liangliang; Pan, Ding; Shao, Lihua; Zheng, Yajun; Hao, Wenhui; Kan, Yu; Cao, Jiawei; Yu, Haotong; Liu, Jing","year":2023,"journal":"Frontiers in pharmacology, 14, 1225256","doi":"10.3389/fphar.2023.1225256","pmid":"37601067","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07622","title":"Two Novel Angiotensin I-Converting Enzyme (ACE) Inhibitory Peptides from Rice (Oryza sativa L.) Bran Protein.","authors":"Zhang, Lingyu; Miao, Jianyin; Guo, Junbin; Liu, Jie; Xia, Zhen; Chen, Bingbing; Ma, Feng; Cao, Yong","year":2023,"journal":"Journal of agricultural and food chemistry, 71(9), 4153-4162","doi":"10.1021/acs.jafc.2c07270","pmid":"36812450","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Two novel peptides were identified from rice bran protein hydrolysate: FDGSPVGY (840.4 Da) with an ACE-inhibitory IC50 of 0.079 mg/mL (94.05 μM), and VFDGVLRPGQ (1086.6 Da) with an IC50 of 0.093 mg/mL (85.59 μM).\n\nMolecular docking analysis revealed that both peptides interact with the ACE receptor protein through hydrogen bonding and hydrophobic interactions, providing a structural explanation for their inhibitory activity.\n\nIn EA.hy926 endothelial cells, both peptides promoted nitric oxide (NO) release and reduced endothelin-1 (ET-1) levels — two complementary mechanisms that would lower blood pressure by relaxing blood vessels and reducing vasoconstriction.","whyItMatters":"Hypertension affects over a billion people worldwide and is a leading risk factor for heart disease and stroke. While pharmaceutical ACE inhibitors are effective, they can cause side effects like chronic cough. Bioactive peptides from food sources like rice bran could offer natural alternatives or complementary approaches to blood pressure management, while also adding value to an agricultural byproduct that is often discarded or underutilized.","specificNumbers":"","methodology":"Rice bran protein hydrolysate was separated using ultrafiltration to isolate small peptide fractions, then further purified by reversed-phase HPLC. Peptide sequences were identified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). ACE inhibitory activity was measured in vitro to determine IC50 values. Molecular docking simulations modeled how the peptides interact with the ACE enzyme. Cellular effects were tested in EA.hy926 human endothelial cells, measuring nitric oxide release and endothelin-1 levels.","limitations":"This is entirely an in vitro and cell-based study — no animal or human trials were conducted. ACE inhibition in a test tube does not guarantee blood pressure reduction in a living organism, as peptides may be degraded during digestion or fail to reach the bloodstream. The IC50 values, while measurable, are relatively high compared to pharmaceutical ACE inhibitors. The EA.hy926 cell line is an approximation of human blood vessel cells and may not fully represent in vivo vascular biology. Bioavailability of these peptides after oral consumption is unknown."},{"rthcId":"RPEP-07623","title":"Pharmacokinetic similarity study comparing the biosimilar candidate, LY05008, with its reference product dulaglutide in healthy Chinese male subjects.","authors":"Zhang, Qin; Sun, Cheng; Wu, Jinying; Wu, Juan; Zhang, Xuan; Liu, Yueyue; Dou, Changlin; Qin, Huilin; Zhang, Qian; Zhou, Renpeng; Hu, Wei","year":2023,"journal":"Expert opinion on biological therapy, 23(8), 727-735","doi":"10.1080/14712598.2023.2189009","pmid":"36880118","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07624","title":"A Dendrimer Peptide (KK2DP7) Delivery System with Dual Functions of Lymph Node Targeting and Immune Adjuvants as a General Strategy for Cancer Immunotherapy.","authors":"Zhang, Rui; Tang, Lin; Wang, Yusi; Tian, Yaomei; Wu, Siwen; Zhou, Bailing; Dong, Chunyan; Zhao, Binyan; Yang, Yuling; Xie, Daoyuan; Yang, Li","year":2023,"journal":"Advanced science (Weinheim, Baden-Wurttemberg, Germany), 10(15), e2300116","doi":"10.1002/advs.202300116","pmid":"36950751","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07625","title":"Nanopore discrimination and sensitive plasma detection of multiple natriuretic peptides: The representative biomarker of human heart failure.","authors":"Zhang, Shaoxia; Wang, Yunjiao; Song, Dandan; Guan, Sarah; Zhou, Daming; Gong, Linyu; Liang, Liyuan; Guan, Xiyun; Wang, Liang","year":2023,"journal":"Biosensors & bioelectronics, 231, 115299","doi":"10.1016/j.bios.2023.115299","pmid":"37054600","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07626","title":"Effect of multi-mode sweep frequency ultrasound pretreatment on properties of the zeins and ACE inhibitory peptides activity of the hydrolysates.","authors":"Zhang, Shuang; Xu, Zhiqiang; Zheng, Wenbin; Pan, Qiang; Zhu, Yinglian","year":2023,"journal":"Food chemistry, 407, 135126","doi":"10.1016/j.foodchem.2022.135126","pmid":"36493471","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07627","title":"Definitive Treatment of Brain Metastases From a Neuroendocrine Tumor With Peptide Receptor Radionuclide Therapy With 177Lutetium DOTATATE: A Case Report.","authors":"Zhang, Vivian; Taparra, Kekoa; Fisher, George; Aparici, Carina; Soltys, Scott G","year":2023,"journal":"Cureus, 15(9), e45327","doi":"10.7759/cureus.45327","pmid":"37849592","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07628","title":"A novel antimicrobial peptide Scyreptin1-30 from Scylla paramamosain exhibiting potential therapy of Pseudomonas aeruginosa early infection in a mouse burn wound model.","authors":"Zhang, Weibin; An, Zhe; Bai, Yuqi; Zhou, Ying; Chen, Fangyi; Wang, Ke-Jian","year":2023,"journal":"Biochemical pharmacology, 218, 115917","doi":"10.1016/j.bcp.2023.115917","pmid":"37952897","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07629","title":"Production of marine bacterial metalloprotease A69 and evaluation of its potential in preparing soybean peptides with angiotensin-converting enzyme-inhibitory activity.","authors":"Zhang, Xia; Zhao, Wen-Xiao; Wang, Yan; Cheng, Jun-Hui; Bao, Kai; He, Jin; Chen, Xiu-Lan","year":2023,"journal":"Journal of the science of food and agriculture, 103(14), 7153-7163","doi":"10.1002/jsfa.12797","pmid":"37338325","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07630","title":"Short-term cost-effectiveness analysis of tirzepatide for the treatment of type 2 diabetes in the United States.","authors":"Zhang, Xiaotong; McAdam Marx, Carrie","year":2023,"journal":"Journal of managed care & specialty pharmacy, 29(3), 276-284","doi":"10.18553/jmcp.2023.29.3.276","pmid":"36840958","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07631","title":"High-Throughput Screening of Stapled Helical Peptides in Drug Discovery.","authors":"Zhang, Yiwei; Guo, Jiabei; Cheng, Jiongjia; Zhang, Zhenghua; Kang, Fenghua; Wu, Xiaoxing; Chu, Qian","year":2023,"journal":"Journal of medicinal chemistry, 66(1), 95-106","doi":"10.1021/acs.jmedchem.2c01541","pmid":"36580278","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07632","title":"Effects of a Dulaglutide plus Calorie-Restricted Diet versus a Calorie-Restricted Diet on Visceral Fat and Metabolic Profiles in Women with Polycystic Ovary Syndrome: A Randomized Controlled Trial.","authors":"Zhang, Yuqin; Qu, Zhihua; Lu, Ting; Shao, Xiaowen; Cai, Meili; Dilimulati, Diliqingna; Gao, Xinxin; Mao, Weiqing; Hu, Fan; Su, Lili; Liao, Qiong; Han, Ting; Zhang, Manna; Qu, Shen","year":2023,"journal":"Nutrients, 15(3)","doi":"10.3390/nu15030556","pmid":"36771262","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07633","title":"GLP-1RAs caused gastrointestinal adverse reactions of drug withdrawal: a system review and network meta-analysis.","authors":"Zhang, Ziqi; Zhang, Qiling; Tan, Ying; Chen, Yu; Zhou, Xiqiao; Liu, Su; Yu, Jiangyi","year":2023,"journal":"Frontiers in endocrinology, 14, 1149328","doi":"10.3389/fendo.2023.1149328","pmid":"37484944","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07634","title":"Prospect of acromegaly therapy: molecular mechanism of clinical drugs octreotide and paltusotine.","authors":"Zhao, Jie; Fu, Hong; Yu, Jingjing; Hong, Weiqi; Tian, Xiaowen; Qi, Jieyu; Sun, Suyue; Zhao, Chang; Wu, Chao; Xu, Zheng; Cheng, Lin; Chai, Renjie; Yan, Wei; Wei, Xiawei; Shao, Zhenhua","year":2023,"journal":"Nature communications, 14(1), 962","doi":"10.1038/s41467-023-36673-z","pmid":"36810324","tags":["somatostatin","octreotide"],"studyType":"structural-biology","evidenceStrength":"moderate-preclinical","keyFinding":"Cryo-EM analysis of SSTR2-Gi protein complexes revealed the detailed binding modes and activation mechanisms for both octreotide (a peptide analog) and paltusotine (a small molecule). The two drugs show distinct signal bias profiles — meaning they activate different downstream signaling pathways to different degrees despite binding the same receptor.\n\nThe structural data explains the molecular basis of subtype selectivity (why these drugs prefer SSTR2 over other somatostatin receptor subtypes) and signal bias (why they trigger some cellular responses more than others). This mechanistic understanding is directly relevant to why a subset of acromegaly patients have poor responses to current somatostatin analogs.","whyItMatters":"Acromegaly and neuroendocrine tumors are treated with somatostatin analogs, but up to 30% of patients respond poorly. Understanding exactly how these drugs interact with the receptor at the atomic level — and why octreotide and paltusotine produce different signaling patterns — is essential for designing next-generation drugs that work for more patients. This is also the first structural comparison between a peptide drug and a small molecule drug at the same receptor.","specificNumbers":"Cryo-EM structures of SSTR2-Gi complexes with octreotide and paltusotine; distinct signal bias profiles; subtype selectivity mechanism resolved","methodology":"Cryo-electron microscopy analysis of SSTR2-Gi protein complexes bound to octreotide and paltusotine. Pharmacological characterization of signal bias profiles through evaluation of drug-induced receptor activation, G-protein coupling, and downstream signaling. Structural comparison to elucidate mechanisms of ligand recognition, subtype selectivity, and biased signaling.","limitations":"In vitro structural and pharmacological study only; no patient data or clinical outcomes; static cryo-EM snapshots; purified protein system may not fully reflect in vivo receptor behavior."},{"rthcId":"RPEP-07635","title":"Targeting lactate metabolism and immune interaction in breast tumor via protease-triggered delivery.","authors":"Zhao, Pengfei; Wang, Shuang; Jiang, Jizong; Gao, Yanrong; Wang, Yuewei; Zhao, Yuge; Zhang, Jiaxin; Zhang, Meng; Huang, Yongzhuo","year":2023,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 358, 706-717","doi":"10.1016/j.jconrel.2023.05.024","pmid":"37207796","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07636","title":"Thymosin β4 Alleviates Autoimmune Dacryoadenitis via Suppressing Th17 Cell Response.","authors":"Zhao, Xiaoyu; Li, Na; Yang, Ning; Mi, Baoyue; Dang, Weiyu; Sun, Deming; Ma, Shanshan; Nian, Hong; Wei, Ruihua","year":2023,"journal":"Investigative ophthalmology & visual science, 64(11), 3","doi":"10.1167/iovs.64.11.3","pmid":"37531112","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07637","title":"Engineered Histidine-Rich Peptides Enhance Endosomal Escape for Antibody-Targeted Intracellular Delivery of Functional Proteins.","authors":"Zhao, Yan; Jiang, Haolin; Yu, Jiazhen; Wang, Luyao; Du, Juanjuan","year":2023,"journal":"Angewandte Chemie (International ed. in English), 62(38), e202304692","doi":"10.1002/anie.202304692","pmid":"37283024","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07638","title":"Investigation of High Molecular Weight Size Variant Formation in Antibody-Drug Conjugates: Microbial Transglutaminase-Mediated Crosslinking.","authors":"Zhao, Yimeng; Kim, Sunnie; Zheng, Xiang; Kim, Se Hyun; Han, Amy; Chen, Tse-Hong; Wang, Serena; Zhong, Jieqiang; Qiu, Haibo; Li, Ning","year":2023,"journal":"Journal of pharmaceutical sciences, 112(10), 2629-2636","doi":"10.1016/j.xphs.2023.08.006","pmid":"37586591","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07639","title":"Glp-1 Receptor Agonists Regulate the Progression of Diabetes Mellitus Complicated with Fatty Liver by Down-regulating the Expression of Genes Related to Lipid Metabolism.","authors":"Zheng, Shuihong; Huang, Huaying; Chen, Heye; Liu, Yanfen","year":2023,"journal":"Applied biochemistry and biotechnology, 195(8), 5238-5251","doi":"10.1007/s12010-023-04505-x","pmid":"37140780","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07640","title":"A long-acting GDF15 analog causes robust, sustained weight loss and reduction of food intake in an obese nonhuman primate model.","authors":"Zheng, Songmao; Polidori, David; Wang, Yuanping; Geist, Brian; Lin-Schmidt, Xiefan; Furman, Jennifer L; Nelson, Serena; Nawrocki, Andrea R; Hinke, Simon A","year":2023,"journal":"Clinical and translational science, 16(8), 1431-1444","doi":"10.1111/cts.13543","pmid":"37154518","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07641","title":"MOTS-c: A promising mitochondrial-derived peptide for therapeutic exploitation.","authors":"Zheng, Yuejun; Wei, Zilin; Wang, Tianhui","year":2023,"journal":"Frontiers in endocrinology, 14, 1120533","doi":"10.3389/fendo.2023.1120533","pmid":"36761202","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"MOTS-c is encoded by the 12S rRNA region of the mitochondrial genome and is expressed across multiple tissues and found in blood plasma. Key properties: translocates from mitochondria to the nucleus during metabolic stress to regulate gene expression, improves glucose metabolism in skeletal muscle, plasma levels decrease with age, and demonstrates benefits in preclinical models of diabetes, obesity, insulin resistance, cardiovascular disease, inflammation, and aging. The review also discusses synthetic biology approaches for MOTS-c production and delivery.","whyItMatters":"MOTS-c represents a paradigm shift in peptide biology — the idea that mitochondria communicate with the nucleus through peptide signals was revolutionary when discovered. The fact that MOTS-c levels decline with age and that supplementing it can improve metabolic function suggests it could address the root metabolic dysfunction underlying multiple age-related diseases simultaneously. Rather than treating diabetes, obesity, and cardiovascular disease separately, MOTS-c targets the underlying mitochondrial-metabolic axis.","specificNumbers":"","methodology":"Narrative review of the published literature on MOTS-c, covering its discovery, molecular mechanisms (mitochondrial-to-nuclear translocation, gene regulation), physiological functions, disease applications, and potential therapeutic development strategies including synthetic biology approaches.","limitations":"Most evidence for MOTS-c's therapeutic potential comes from preclinical studies (cell culture and animal models). No clinical trials have been reported. The mechanisms by which MOTS-c enters the nucleus and regulates gene expression are not fully characterized. How MOTS-c is released from mitochondria into the bloodstream (where it's detectable as a circulating peptide) is unclear. Manufacturing challenges for a 16-amino-acid mitochondrial peptide are acknowledged but not solved. The decline in MOTS-c with age is documented but whether supplementation can reverse age-related metabolic decline in humans is unknown."},{"rthcId":"RPEP-07642","title":"Emerging roles of oxyntomodulin-based glucagon-like peptide-1/glucagon co-agonist analogs in diabetes and obesity.","authors":"Zhihong, Yao; Chen, Wang; Qianqian, Zhu; Lidan, Sun; Qiang, Zhou; Jing, Han; Wenxi, Wang; Bhawal, Ruchika","year":2023,"journal":"Peptides, 162, 170955","doi":"10.1016/j.peptides.2023.170955","pmid":"36669563","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07643","title":"Effects of dietary supplementation with bioactive peptides derived from rapeseed protein on the growth performance, serum biochemistry and faecal micro-organism composition of weaned piglets.","authors":"Zhong, Xiaoxia; Lin, Peiwen; Yao, Yanchu; Liu, Zhiyun; Zhou, Xiaorong; Guan, Xiaofeng; Huang, Jinxiu","year":2023,"journal":"Journal of animal physiology and animal nutrition, 107(3), 867-877","doi":"10.1111/jpn.13796","pmid":"36541276","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07644","title":"Tat-NTS peptide protects neurons against cerebral ischemia-reperfusion injury via ANXA1 SUMOylation in microglia.","authors":"Zhou, Huijuan; Yan, Lulu; Huang, Hezhou; Li, Xing; Xia, Qian; Zheng, Lu; Shao, Bin; Gao, Qian; Sun, Ning; Shi, Jing","year":2023,"journal":"Theranostics, 13(15), 5561-5583","doi":"10.7150/thno.85390","pmid":"37908731","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07645","title":"Preparation, Purification and Characterization of Antibacterial and ACE Inhibitory Peptides from Head Protein Hydrolysate of Kuruma Shrimp, Marsupenaeus japonicus.","authors":"Zhou, Jie; Han, Qiuyu; Koyama, Tomoyuki; Ishizaki, Shoichiro","year":2023,"journal":"Molecules (Basel, Switzerland), 28(2)","doi":"10.3390/molecules28020894","pmid":"36677951","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"After enzymatic hydrolysis and two rounds of chromatographic purification, researchers identified two key peptides from kuruma shrimp head protein. The antibacterial peptide VTVP showed minimum inhibitory concentration (MIC) values ranging from 1.62 to 8.03 mM against all tested pathogens. The ACE inhibitory peptide ARL/I demonstrated an IC50 value of 125.58 µM and was confirmed as a competitive inhibitor through Lineweaver-Burk analysis.\n\nMolecular docking revealed that ARL/I binds to ACE primarily through hydrogen bonds and forms a coordinate bond with the zinc ion at the enzyme's active site. Importantly, neither peptide showed hemolytic activity against rabbit red blood cells, indicating a favorable safety profile.","whyItMatters":"Seafood processing generates enormous amounts of waste, including shrimp heads rich in protein. Finding valuable bioactive peptides in this waste stream addresses both sustainability concerns and the need for new antibacterial and blood pressure-lowering agents, particularly as antibiotic resistance grows.","specificNumbers":"","methodology":"Shrimp heads were hydrolyzed with papain enzyme at 50°C for 4 hours. The resulting protein hydrolysate was purified through two stages of reversed-phase high-performance liquid chromatography (RP-HPLC). Active peptides were identified using LC-MS/MS. Antibacterial activity was measured by minimum inhibitory concentration (MIC), ACE inhibition was assessed with IC50 values and kinetic analysis, and molecular docking simulations modeled peptide-enzyme interactions.","limitations":"This was a laboratory study only — the peptides were not tested in living organisms for blood pressure reduction or infection treatment. The antibacterial testing was limited to a set of selected pathogens. Stability of these peptides during digestion and their bioavailability in the human body remain unknown."},{"rthcId":"RPEP-07646","title":"Identification and Screening of Potential ACE2 Activating Peptides from Soybean Protein Isolate Hydrolysate against Ang II-Induced Endothelial Dysfunction.","authors":"Zhou, Minzhi; Song, Tianyuan; Li, Wen; Huang, Mingtao; Zheng, Lin; Zhao, Mouming","year":2023,"journal":"Journal of agricultural and food chemistry, 71(31), 11957-11969","doi":"10.1021/acs.jafc.3c03013","pmid":"37501259","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07647","title":"Treatment patterns for patients initiating novel acute migraine specific medications (nAMSMs) in the context of monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway.","authors":"Zhou, Zifan; Urman, Robert; Gill, Karminder; Park, Andrew S; Vuvu, Fiston; Patel, Leah B; Lu, Jingsong; Wade, Rolin L; Frerichs, Lindsay; Bensink, Mark E","year":2023,"journal":"The journal of headache and pain, 24(1), 153","doi":"10.1186/s10194-023-01678-y","pmid":"37946113","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07648","title":"Targeting NK-1R attenuates renal fibrosis via modulating inflammatory responses and cell fate in chronic kidney disease.","authors":"Zhu, Enyi; Liu, Yang; Zhong, Ming; Liu, Yu; Jiang, Xi; Shu, Xiaorong; Li, Na; Guan, Hui; Xia, Yin; Li, Jinhong; Lan, Hui-Yao; Zheng, Zhihua","year":2023,"journal":"Frontiers in immunology, 14, 1142240","doi":"10.3389/fimmu.2023.1142240","pmid":"37033943","tags":["neuropeptides","kidney-disease"],"studyType":"human-and-animal","evidenceStrength":"moderate","keyFinding":"The neuropeptide substance P (SP) and its receptor NK-1R were found to be elevated in both patients with chronic kidney disease and in mice with induced kidney obstruction. Higher SP/NK-1R levels correlated with worse kidney fibrosis and declining kidney function.\n\nAdding substance P to mice with kidney obstruction worsened inflammation and fibrosis, while genetically knocking out NK-1R or blocking it with a drug significantly reduced these effects. The researchers uncovered the mechanism: a transcription factor called TFAP4 drives NK-1R production, and once substance P activates NK-1R, it triggers the JNK/p38 signaling pathways. This causes kidney tubular cells to stop growing, undergo programmed cell death, and switch on scar-producing genes.","whyItMatters":"This study bridges neuropeptide biology and kidney disease in a way that has direct therapeutic implications. Substance P is best known for its role in pain signaling, but this research shows it also drives kidney inflammation and scarring through NK-1R. Importantly, NK-1R antagonists already exist as approved drugs for other conditions (such as the anti-nausea drug aprepitant), which means repurposing these medications for chronic kidney disease could be a relatively fast path to clinical testing.","specificNumbers":"SP and NK-1R elevated in CKD patients · serum SP correlated with fibrosis severity · NK-1R knockout mice protected from UUO-induced fibrosis · JNK/p38 pathway activation confirmed · TFAP4 identified as NK-1R transcriptional driver","methodology":"This was a multi-approach study combining human clinical samples with animal and cell models. The researchers analyzed kidney biopsy tissue and serum from patients with and without CKD. They used NK-1R knockout mice, substance P treatment, and a pharmacological NK-1R antagonist in a unilateral ureteral obstruction (UUO) mouse model of kidney fibrosis. Cell-level mechanisms were explored using NK-1R-overexpressing human kidney tubular cells (HK-2). Promoter binding analysis identified TFAP4 as the transcription factor driving NK-1R expression.","limitations":"The mouse model (UUO) represents obstructive kidney disease, which is only one cause of CKD and may not fully represent other forms like diabetic or hypertensive nephropathy. The human component was observational (biopsy and serum analysis), so it shows correlation but not causation in people. Specific patient numbers and clinical outcomes were not detailed in the abstract."},{"rthcId":"RPEP-07649","title":"Glucagon-like peptide-1 receptor agonists as a disease-modifying therapy for knee osteoarthritis mediated by weight loss: findings from the Shanghai Osteoarthritis Cohort.","authors":"Zhu, Hongyi; Zhou, Lenian; Wang, Qiuke; Cai, Qianying; Yang, Fan; Jin, Hanqiang; Chen, Yiwei; Song, Yanyan; Zhang, Changqing","year":2023,"journal":"Annals of the rheumatic diseases, 82(9), 1218-1226","doi":"10.1136/ard-2023-223845","pmid":"37258065","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07650","title":"Oxytocin and Women Postpartum Depression: A Systematic Review of Randomized Controlled Trials.","authors":"Zhu, Jialei; Jin, Jing; Tang, Jing","year":2023,"journal":"Neuropsychiatric disease and treatment, 19, 939-947","doi":"10.2147/NDT.S393499","pmid":"37096027","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 6 RCTs involving 195 women, oxytocin's effects on postpartum depression were mixed. For emotion: one trial showed oxytocin alleviated depressive mood, two showed no effect (though one found reduced negative thoughts in healthy mothers), and one actually showed oxytocin worsened depression. For cognition: four trials generally found oxytocin enhanced postpartum women's perception of their relationship with their infants. The review concluded that oxytocin may improve mother-infant cognitive bonding but its effects on depressive mood remain uncertain and contradictory.","whyItMatters":"Postpartum depression affects roughly 10-15% of new mothers and can severely impair mother-infant bonding and child development. Since oxytocin is naturally released during breastfeeding and skin-to-skin contact, it seemed like a logical therapeutic target. This review reveals a more nuanced reality: oxytocin may help mothers perceive their relationship with their baby more positively, but it doesn't reliably improve depressive mood — and in one case, actually worsened it.","specificNumbers":"6 RCTs · 195 women total · 1 trial: improved mood · 2 trials: no mood effect · 1 trial: worsened depression · 4 trials: improved mother-infant cognitive perception","methodology":"Systematic review of randomized controlled trials. Databases searched: PubMed, Web of Science, Cochrane Library, and EmBase from inception through April 2022. Six RCTs meeting inclusion criteria were analyzed qualitatively, with effects categorized into emotional outcomes and cognitive outcomes.","limitations":"Very small total sample size (195 women across 6 studies). The review could not perform a meta-analysis due to heterogeneity in outcomes and measurements across studies. Different oxytocin doses, routes, and timing were used across trials. The finding that oxytocin worsened depression in one trial raises safety concerns that need further investigation. Only studies through April 2022 were included."},{"rthcId":"RPEP-07651","title":"Efficacy and safety of semaglutide in non-alcoholic fatty liver disease.","authors":"Zhu, Kai; Kakkar, Rohan; Chahal, Daljeet; Yoshida, Eric M; Hussaini, Trana","year":2023,"journal":"World journal of gastroenterology, 29(37), 5327-5338","doi":"10.3748/wjg.v29.i37.5327","pmid":"37899788","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07652","title":"Pancreatic polypeptide revisited: Potential therapeutic effects in obesity-diabetes.","authors":"Zhu, Wuyun; Tanday, Neil; Flatt, Peter R; Irwin, Nigel","year":2023,"journal":"Peptides, 160, 170923","doi":"10.1016/j.peptides.2022.170923","pmid":"36509169","tags":["gut-peptides","pancreatic-polypeptide"],"studyType":"Review","evidenceStrength":"low-moderate","keyFinding":"Pancreatic polypeptide (PP) — a hormone released from the pancreas — suppresses appetite by activating Y4 receptors in the brain, producing satiety in both animals and humans. Beyond appetite control, PP also affects the insulin-producing beta cells of the pancreas, with an acute insulin-suppressing effect.\n\nIntriguingly, sustained activation of related Y-family receptors (Y1) improves beta-cell survival, preserves beta-cell identity, and enhances insulin secretion — raising the possibility that long-acting Y4 agonists could provide similar anti-diabetic benefits. However, PP's extremely short half-life in the blood has prevented its therapeutic development. Engineering enzyme-resistant, long-acting versions will be necessary to test its clinical potential.","whyItMatters":"In the era of GLP-1 drugs, there's intense interest in other gut and pancreatic peptides that could combat obesity and diabetes. PP represents an underexplored pathway — it reduces appetite through a different receptor system (Y4) than GLP-1, and it may also protect beta cells. If long-acting PP analogs can be developed, they could complement or combine with existing GLP-1 drugs for enhanced metabolic benefits.","specificNumbers":"PP activates Y4 receptors · induces satiety in animals + humans · acute insulinostatic effect · short circulating half-life (major limitation) · related Y1 activation improves beta-cell function","methodology":"Narrative review synthesizing published preclinical and clinical evidence on PP biology, its receptor pharmacology (Y4R), its effects on appetite and the endocrine pancreas, and the challenges of therapeutic development. The authors draw parallels with related NPY family peptides and their receptor signaling pathways.","limitations":"This is a review — no new data presented. Much of the evidence for PP's metabolic effects comes from acute infusion studies in animals. Long-acting PP analogs have not yet been developed or tested, so the therapeutic potential remains theoretical. The comparison to Y1 receptor effects is inferential rather than proven for Y4."},{"rthcId":"RPEP-07653","title":"Study of the skin-penetration promoting effect and mechanism of combined system of curcumin liposomes prepared by microfluidic chip and skin penetrating peptides TD-1 for topical treatment of primary melanoma.","authors":"Zhu, Yingyin; Xiao, Wuqing; Zhong, Wanling; Xi, Cheng; Ye, Jinhong; Zhang, Qing; Wu, Huichao; Du, Shouying","year":2023,"journal":"International journal of pharmaceutics, 643, 123256","doi":"10.1016/j.ijpharm.2023.123256","pmid":"37482229","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07654","title":"Inflammation and Organ Injury the Role of Substance P and Its Receptors.","authors":"Zhu, Zhixing; Bhatia, Madhav","year":2023,"journal":"International journal of molecular sciences, 24(7)","doi":"10.3390/ijms24076140","pmid":"37047113","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07655","title":"EVIDENCE FROM FATAL COVID-19 FOR TARGETING THE BRADYKININ METABOLISM-A SINGLE-CENTER COHORT STUDY.","authors":"Zinn, Sebastian; Talbot, Steven R; Rajapakse, Dammith; Ruskowski, Katharina; Neb, Holger; Adam, Elisabeth H; von Knethen, Andreas; Zacharowski, Kai; Heinicke, Ulrike","year":2023,"journal":"Shock (Augusta, Ga.), 60(6), 727-738","doi":"10.1097/SHK.0000000000002231","pmid":"37878473","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07656","title":"Senotherapeutic peptide treatment reduces biological age and senescence burden in human skin models.","authors":"Zonari, Alessandra; Brace, Lear E; Al-Katib, Kallie; Porto, William F; Foyt, Daniel; Guiang, Mylieneth; Cruz, Edgar Andres Ochoa; Marshall, Bailey; Gentz, Melissa; Guimarães, Gabriela Rapozo; Franco, Octavio L; Oliveira, Carolina R; Boroni, Mariana; Carvalho, Juliana L","year":2023,"journal":"npj aging, 9(1), 10","doi":"10.1038/s41514-023-00109-1","pmid":"37217561","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07657","title":"Amphipathic Cell-Penetrating Peptide-Aided Delivery of Cas9 RNP for In Vitro Gene Editing and Correction.","authors":"Öktem, Mert; Mastrobattista, Enrico; de Jong, Olivier G","year":2023,"journal":"Pharmaceutics, 15(10)","doi":"10.3390/pharmaceutics15102500","pmid":"37896260","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07658","title":"EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD): Executive Summary.","authors":"","year":2024,"journal":"Diabetologia, 67(11), 2375-2392","doi":"10.1007/s00125-024-06196-3","pmid":"38869512","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The guidelines establish a comprehensive framework for MASLD management with several key recommendations:\n\n- Case-finding using non-invasive tests (FIB-4 score, then transient elastography) in patients with cardiometabolic risk factors\n- Lifestyle modification as the foundation: weight loss, dietary changes, exercise, no alcohol\n- Incretin-based therapies (semaglutide, tirzepatide) recommended for optimal management of comorbidities in MASLD patients with type 2 diabetes or obesity\n- Resmetirom recommended as MASH-targeted treatment for non-cirrhotic patients with significant fibrosis (stage ≥2)\n- Bariatric surgery as an option for MASLD patients with obesity\n- No MASH-targeted pharmacotherapy recommended for cirrhotic stage","whyItMatters":"This is a landmark guideline that formally positions incretin-based peptide therapies as part of standard MASLD management — a significant expansion beyond their original diabetes and obesity indications. With MASLD affecting an estimated 30% of the global adult population, the explicit recommendation of semaglutide and tirzepatide in these guidelines will drive widespread prescribing and may accelerate dedicated clinical trials for liver-specific outcomes with these peptide drugs.","specificNumbers":"","methodology":"This is a joint clinical practice guideline from three European medical societies: EASL (liver), EASD (diabetes), and EASO (obesity). The guideline was developed through systematic evidence review and expert consensus, providing graded recommendations for prevention, screening, diagnosis, and treatment of MASLD.","limitations":"As guidelines rather than original research, these recommendations are limited by the evidence available at the time of writing. The liver-specific outcomes of semaglutide and tirzepatide in MASLD are still being studied in dedicated trials — the recommendation is based largely on their metabolic benefits. Resmetirom is the only specifically liver-targeted drug recommended, and only for non-cirrhotic patients. Implementation may vary widely based on local healthcare resources and drug availability."},{"rthcId":"RPEP-07659","title":"EASL-EASD-EASO Clinical Practice Guidelines on the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).","authors":"","year":2024,"journal":"Obesity facts, 17(4), 374-444","doi":"10.1159/000539371","pmid":"38852583","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07660","title":"EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD).","authors":"","year":2024,"journal":"Journal of hepatology, 81(3), 492-542","doi":"10.1016/j.jhep.2024.04.031","pmid":"38851997","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07661","title":"Camilleri 2024 Newer Pharmacological Interventions Dire","authors":"","year":2024,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07662","title":"Dal 2024 Pdc Cathepsin B Overexpression","authors":"","year":2024,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07663","title":"Fattori 2024 Nociceptortomacrophage Communication Through Cg","authors":"","year":2024,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07664","title":"Geer 2024 Acromegaly Cancer Cohort","authors":"","year":2024,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07665","title":"Perrey 2024 Novel Ox1r Antagonist Sud","authors":"","year":2024,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07666","title":"GLP-1 receptor agonists in patients with chronic kidney disease and either overweight or obesity.","authors":"Abasheva, Daria; Ortiz, Alberto; Fernandez-Fernandez, Beatriz","year":2024,"journal":"Clinical kidney journal, 17(Suppl 2), 19-35","doi":"10.1093/ckj/sfae296","pmid":"39583142","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07667","title":"Effect of New Antidiabetics on Steatosis in Nerve Tissues and Nerve Conduction Velocity: Possible Role of Nerve Growth Factor (NGF)/Synaptophysin and Nrf2/HO-1 Pathways.","authors":"Abdel-Halim, Nehal H M; Eid, Elsayed A; Yehya, Yomna M; Taha, Medhat; Mosa, Ahmed A H; Ammar, Omar; Nasr, Ahmed N A; Hussin, Emadeldeen; Hussein, Abdelaziz M","year":2024,"journal":"Cureus, 16(7), e65726","doi":"10.7759/cureus.65726","pmid":"39211670","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07668","title":"Institutional experience on the impact of glucagon-like peptide-1 agonists (GLP-1) on glycemic control and weight loss in patients with type 2 diabetes at the Dubai Diabetes Center, United Arab Emirates.","authors":"Abdelmannan, Dima; AlBuflasa, Manal; Ajlouni, Heitham; Zidan, Marwan; Rahman, Farya; Farooqi, Muhammad Hamed; Enrique Caballero, A","year":2024,"journal":"Diabetes research and clinical practice, 207, 111045","doi":"10.1016/j.diabres.2023.111045","pmid":"38070546","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07669","title":"Enhancement of an entomopathogenic fungal virulence against the seedcorn maggot, Delia platura, by suppressing immune responses with a bacterial culture broth of Photorhabdus temperata subsp. temperata.","authors":"Abdisa, Eticha; Park, Hyunje; Kwon, Jiyoon; Jin, Gahyeon; Esmaeily, Mojtaba; Kim, Yonggyun","year":2024,"journal":"Archives of insect biochemistry and physiology, 115(3), e22103","doi":"10.1002/arch.22103","pmid":"38517449","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07670","title":"Comparing regional brain uptake of incretin receptor agonists after intranasal delivery in CD-1 mice and the APP/PS1 mouse model of Alzheimer's disease.","authors":"Abdulhameed, Noor; Babin, Alice; Hansen, Kim; Weaver, Riley; Banks, William A; Talbot, Konrad; Rhea, Elizabeth M","year":2024,"journal":"Alzheimer's research & therapy, 16(1), 173","doi":"10.1186/s13195-024-01537-1","pmid":"39085976","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07671","title":"Tirzepatide-Related Acute Liver Injury.","authors":"Abdullah, Irrum; El-Ghousain, Husam; Alenezi, Meshaan","year":2024,"journal":"European journal of case reports in internal medicine, 11(9), 004813","doi":"10.12890/2024_004813","pmid":"39247248","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07672","title":"Single Disulfide Bond in Host Defense Thanatin Analog Peptides: Antimicrobial Activity, Atomic-Resolution Structures and Target Interactions.","authors":"Abdullah, Swaleeha Jaan; Guan, Jia Sheng; Mu, Yuguang; Bhattacharjya, Surajit","year":2024,"journal":"International journal of molecular sciences, 26(1)","doi":"10.3390/ijms26010051","pmid":"39795909","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The disulfide bond in the designed thanatin analog peptide VF16QK is essential for its antibacterial activity. Only the disulfide-bonded form showed bacterial growth inhibition, while the Cys-to-Ser variant (VF16QKSer) lacking the disulfide bond was inactive. The two forms showed vastly different 3D structures, bacterial membrane permeabilization abilities, LPS-outer membrane interactions, and binding to the target periplasmic protein LptAm. This contrasts with other β-hairpin antimicrobial peptides (protegrin, tachyplesin) where disulfide bonds are dispensable.","whyItMatters":"With antibiotic resistance rising globally, antimicrobial peptides offer a promising alternative. Understanding exactly which structural features are essential for activity — like the disulfide bond in thanatin — is critical for designing next-generation peptide antibiotics that can kill drug-resistant bacteria.","specificNumbers":"16-residue peptide · single disulfide bond · active against E. coli and K. pneumoniae · disulfide bond essential (vs. dispensable in protegrin/tachyplesin)","methodology":"Researchers designed a 16-residue thanatin analog (VF16QK) and a variant with the disulfide bond removed (VF16QKSer). They compared antibacterial activity via growth inhibition assays, measured bacterial membrane permeabilization, determined atomic-resolution 3D structures, assessed LPS-outer membrane and LptAm target protein interactions, and performed computational docking analysis of LPS-peptide complexes.","limitations":"This is a structural and in vitro study focused on two peptide variants. Activity was tested against a limited range of bacterial species. In vivo efficacy, toxicity, stability, and pharmacokinetic properties were not evaluated."},{"rthcId":"RPEP-07673","title":"GLP-1 Receptor Agonists: Beyond Diabetes-What the Neurosurgeon Needs to Know.","authors":"Abdulrazeq, Hael; Taman, Mazen; Ali, Rohaid; Doberstein, Cody; Sullivan, Patricia; Sampath, Prakash; Telfeian, Albert; Gokaslan, Ziya; Fridley, Jared; Asaad, Wael","year":2024,"journal":"Neurosurgery practice, 5(3), e00098","doi":"10.1227/neuprac.0000000000000098","pmid":"39959894","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07674","title":"Self-Assembled Food Peptides: Recent Advances and Perspectives in Food and Health Applications.","authors":"Abioye, Raliat O; Camaño Echavarría, Jairo Andrés; Obeme-Nmom, Joy I; Yiridoe, Martha S; Ogunrinola, Oluwaseyi A; Ezema, Matthew D; Udenigwe, Chibuike C","year":2024,"journal":"Journal of agricultural and food chemistry, 72(15), 8372-8379","doi":"10.1021/acs.jafc.4c01385","pmid":"38579274","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07675","title":"Evaluating Modern Therapeutic Interventions for Migraine Management: A Systematic Review.","authors":"Achiatar, Lovett S; Nasir, Iqra; Zia, Zainab; Jameel, Hind; Raut, Yogesh; Sher, Hamza; Shehryar, Abdullah; Shafqat, Benazir; Palekar, Khadija A; Nisar, Lyba; Rehman, Abdur; Khan, Moosa","year":2024,"journal":"Cureus, 16(8), e67397","doi":"10.7759/cureus.67397","pmid":"39310458","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07676","title":"Easy-to-Engineer Flexible Nanoelectrode Sensor from an Inexpensive Overhead Projector Sheet for Sweat Neuropeptide-Y Detection.","authors":"Aerathupalathu Janardhanan, Jayakrishnan; She, Jia-Wei; Yu, Hsiao-Hua","year":2024,"journal":"ACS applied bio materials, 7(12), 8423-8433","doi":"10.1021/acsabm.4c01229","pmid":"39548983","tags":["diagnostics","neuropeptides"],"studyType":"basic-research","evidenceStrength":"preliminary","keyFinding":"Researchers built an inexpensive, flexible biosensor from a common overhead projector (OHP) sheet that can detect Neuropeptide Y (NPY) in sweat with remarkable sensitivity. The sensor detected NPY across a wide concentration range (1 pg/mL to 1 μg/mL) with a detection limit of just 0.68 pg/mL and good linearity (R² = 0.9841).\n\nThe sensor showed excellent selectivity for NPY even in the presence of other molecules commonly found in sweat (TNF-α, cortisol, IL-6). It maintained stability for 13 days and successfully detected NPY spiked into artificial sweat at 100 pg/mL, demonstrating potential for real-world wearable health monitoring applications.","whyItMatters":"Neuropeptide Y is a stress biomarker linked to cardiovascular regulation, appetite control, and anxiety. Currently, measuring NPY requires blood draws and laboratory analysis. A cheap, flexible sensor that can detect NPY in sweat could enable non-invasive, continuous stress monitoring through a wearable device — imagine a smartwatch patch that tracks your stress peptide levels in real time. The use of inexpensive OHP sheet material makes mass production feasible.","specificNumbers":"Detection range: 1 pg/mL to 1 μg/mL · LOD: 0.68 pg/mL · R² = 0.9841 · 13-day shelf life · Selective against TNF-α, cortisol, IL-6 · Validated in artificial sweat at 100 pg/mL","methodology":"The researchers converted a non-conductive overhead projector sheet into a conductive biosensor platform using a hybrid polymerization method. They first deposited polypyrrole via interfacial polymerization, then electropolymerized conductive polymer nanotubes on top. NPY antibodies were conjugated to the polymer surface using standard coupling chemistry. Detection was performed using chronoamperometry (measuring electrical current changes when NPY binds). The sensor was validated using phosphate-buffered saline and artificial perspiration spiked with known NPY concentrations.","limitations":"The sensor was tested only with artificial sweat spiked with NPY, not with real human sweat samples from actual subjects. The 13-day shelf life is relatively short for a wearable device. The study did not test the sensor in a wearable format on skin. Real sweat contains many more compounds that could interfere with detection. Clinical validation with human subjects is still needed."},{"rthcId":"RPEP-07677","title":"Prolactin Secreting Pituitary Carcinoma and the Role of Peptide Receptor Radionuclide Therapy: A Brief Report.","authors":"Agarwal, Nitish; Verma, Satish Kumar; Gopinathan, Vikram Raj; Sharma, Mehar Chand; Sharma, Anima; Chandra, Sarat P","year":2024,"journal":"Neurology India, 72(4), 871-876","doi":"10.4103/neurol-india.Neurol-India-D-24-00529","pmid":"39216050","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07678","title":"Skeletal muscle mitochondrial dysfunction mediated by Pseudomonas aeruginosa quorum-sensing transcription factor MvfR: reversing effects with anti-MvfR and mitochondrial-targeted compounds.","authors":"Aggarwal, Shifu; Singh, Vijay; Chakraborty, Arijit; Cha, Sujin; Dimitriou, Alexandra; de Crescenzo, Claire; Izikson, Olivia; Yu, Lucy; Plebani, Roberto; Tzika, A Aria; Rahme, Laurence G","year":2024,"journal":"mBio, 15(7), e0129224","doi":"10.1128/mbio.01292-24","pmid":"38860823","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07679","title":"Vasoactive intestinal peptide promotes secretory differentiation and mitigates radiation-induced intestinal injury.","authors":"Agibalova, Tatiana; Hempel, Anneke; Maurer, H Carlo; Ragab, Mohab; Ermolova, Anastasia; Wieland, Jessica; Waldherr Ávila de Melo, Caroline; Heindl, Fabian; Giller, Maximilian; Fischer, Julius Clemens; Tschurtschenthaler, Markus; Kohnke-Ertel, Birgit; Öllinger, Rupert; Steiger, Katja; Demir, Ihsan Ekin; Saur, Dieter; Quante, Michael; Schmid, Roland M; Middelhoff, Moritz","year":2024,"journal":"Stem cell research & therapy, 15(1), 348","doi":"10.1186/s13287-024-03958-z","pmid":"39380035","tags":["vip","gut-regeneration","radiation-injury"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Vasoactive intestinal peptide (VIP) protects the gut from radiation damage by promoting intestinal stem cell differentiation and regeneration. VIP drove intestinal epithelial cells toward a secretory phenotype primarily through the p38 MAPK signaling pathway and modulated the proliferation of Lgr5+ progenitor cells (intestinal stem cells). After radiation injury, these stem cells became more responsive to VIP's effects, and VIP strongly promoted epithelial regeneration. Critically, these findings held in live mice — VIP injections significantly reduced radiation-induced intestinal damage after abdominal irradiation with 12 Gy.","whyItMatters":"Radiation damage to the gut is a serious side effect of cancer treatment, with limited options for protection or repair. This study shows that VIP — a natural peptide already present in the gut's nervous system — can protect intestinal stem cells and accelerate gut repair after radiation. This could lead to new supportive treatments for cancer patients undergoing abdominal radiation therapy.","specificNumbers":"6 Gy irradiation (organoids) · 12 Gy abdominal irradiation (mice) · p38 MAPK pathway · Lgr5+ progenitor cells","methodology":"Researchers grew intestinal organoids (miniature gut structures) from mouse jejunal tissue and treated them with VIP before and after 6 Gy irradiation. They used Lgr5-reporter mice to track intestinal stem cells and their proliferation. For in vivo validation, mice received 12 Gy abdominal irradiation followed by intraperitoneal VIP injections. Analysis included epithelial differentiation markers, stem cell number and activity, and tissue damage assessment.","limitations":"This is an animal study using mice — results need to be validated in humans. The organoid model, while informative, does not fully replicate the complexity of the intact human gut environment including immune cells, blood supply, and the microbiome. The radiation doses and VIP administration protocols would need optimization for clinical translation. Long-term effects of VIP treatment on gut tissue were not assessed."},{"rthcId":"RPEP-07680","title":"Selective Colocalization of GHSR and GLP-1R in a Subset of Hypothalamic Neurons and Their Functional Interaction.","authors":"Aguggia, Julieta; Fernandez, Gimena; Cassano, Daniela; Mustafá, Emilio R; Rodríguez, Silvia S; Cantel, Sonia; Fehrentz, Jean-Alain; Raingo, Jesica; Schiöth, Helgi B; Habib, Abdella M; De Francesco, Pablo N; Perello, Mario","year":2024,"journal":"Endocrinology, 166(1)","doi":"10.1210/endocr/bqae160","pmid":"39737802","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Using GHSR-eGFP reporter mice, fluorescent ghrelin, and anti-GLP-1R antibodies, the team mapped receptor co-expression across the mouse brain. GHSR+ and GLP-1R+ neurons were largely segregated, with the highest overlap in the arcuate nucleus of the hypothalamus, where 15-20% of GHSR+ cells also expressed GLP-1R. RNA-sequencing data from both mouse and human brains confirmed that double-positive cells represent less than 10% of all GHSR+ or GLP-1R+ neurons.\n\nIn patch-clamp experiments, the researchers made the first demonstration that liraglutide-activated GLP-1R inhibits presynaptic calcium channels. Critically, when both receptors were present on the same cell, activating one attenuated the inhibitory effect of the other — showing direct molecular crosstalk between the ghrelin and GLP-1 signaling pathways.","whyItMatters":"GLP-1 receptor agonists like semaglutide and liraglutide are blockbuster drugs for obesity and diabetes, while ghrelin signaling is a major target for appetite research. Understanding how these two opposing systems interact at the cellular level could reveal why some patients respond better to GLP-1 drugs and may open the door to combination therapies that target both pathways simultaneously.","specificNumbers":"","methodology":"The study combined three approaches: (1) anatomical mapping using GHSR-eGFP reporter mice and fluorescent ghrelin paired with anti-GLP-1R antibodies to visualize receptor co-localization; (2) analysis of single-cell RNA-sequencing datasets from mouse and human brains; and (3) patch-clamp electrophysiology in a heterologous expression system to measure how each receptor's activation affects presynaptic calcium channel function.","limitations":"The co-localization mapping was performed primarily in mice, and while human RNA-seq data was also analyzed, direct protein-level co-localization in human brain tissue was not confirmed. The functional crosstalk experiments used a heterologous expression system rather than native neurons, so the magnitude of crosstalk in vivo may differ. The study focused on calcium channel regulation and did not examine downstream effects on feeding behavior."},{"rthcId":"RPEP-07681","title":"Sensory neurons regulate stimulus-dependent humoral immunity in mouse models of bacterial infection and asthma.","authors":"Aguilar, Diane; Zhu, Fengli; Millet, Antoine; Millet, Nicolas; Germano, Patrizia; Pisegna, Joseph; Akbari, Omid; Doherty, Taylor A; Swidergall, Marc; Jendzjowsky, Nicholas","year":2024,"journal":"Nature communications, 15(1), 8914","doi":"10.1038/s41467-024-53269-3","pmid":"39414787","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07682","title":"Glucagon-like peptide1 receptor agonist treatment of cystic fibrosis-related diabetes complicated by obesity: A cases series and literature review.","authors":"Ahmed, Ammar; Ankireddypalli, Anvitha; Harindhanavudhi, Tasma; Moran, Antoinette; Moheet, Amir","year":2024,"journal":"Journal of clinical & translational endocrinology, 38, 100375","doi":"10.1016/j.jcte.2024.100375","pmid":"39764279","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07683","title":"Recent Advances in Smart Self-Assembled Bioinspired Hydrogels: A Bridging Weapon for Emerging Health Care Applications from Bench to Bedside.","authors":"Ahuja, Rishabh; Shivhare, Vaibhav; Konar, Anita Dutt","year":2024,"journal":"Macromolecular rapid communications, 45(17), e2400255","doi":"10.1002/marc.202400255","pmid":"38802265","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07684","title":"Specific intermolecular interaction with sodium glycocholate generates the co-amorphous system showing higher physical stability and aqueous solubility of Y5 receptor antagonist of neuropeptide Y, a brick dust molecule.","authors":"Aikawa, Shohei; Tanaka, Hironori; Ueda, Hiroshi; Maruyama, Masato; Higaki, Kazutaka","year":2024,"journal":"European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 202, 114395","doi":"10.1016/j.ejpb.2024.114395","pmid":"38971200","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07685","title":"Benefit-risk assessment based on number needed to treat and number needed to harm: Atogepant vs. calcitonin gene-related peptide monoclonal antibodies.","authors":"Ailani, Jessica; Lalla, Anjana; Halker Singh, Rashmi B; Holle-Lee, Dagny; Nagy, Krisztian; Kelton, Kari; Piron, Cristiano; Gandhi, Pranav; Pozo-Rosich, Patricia","year":2024,"journal":"Cephalalgia : an international journal of headache, 44(11), 3331024241299377","doi":"10.1177/03331024241299377","pmid":"39558612","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07686","title":"Neutrophil-Lymphocyte Ratio and High Sensitivity C-Reactive Protein as Markers of Heart Failure Severity: A Study at the University of Port-Harcourt Teaching Hospital Heart Failure Clinic.","authors":"Ajala, A O; Dodiyi-Manuel, Sotonye; Oyan, Boma; Ejituwu, Jacquelin; Akpa, Maclean","year":2024,"journal":"West African journal of medicine, 41(5), 562-567","doi":null,"pmid":"39208025","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07687","title":"Effects of Glucagon-Like Peptide-1 Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors on Intima-Media Thickness: Systematic Review and Meta-Analysis.","authors":"Akbari, Abolfazl; Hadizadeh, Shiva; Heidary, Leida","year":2024,"journal":"Journal of diabetes research, 2024, 3212795","doi":"10.1155/2024/3212795","pmid":"38529046","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07688","title":"Chronotropic Responses to GLP-1 Receptor Agonists and Sitagliptin in Atria From Diabetic Rats.","authors":"Akcabag, Esra; Aksoyalp, Zinnet Sevval; Oner, Feride; Bayram, Zeliha; Ozbey, Gul; Nacitarhan, Cahit; Ozdem, Sebahat; Tasatargil, Arda; Ozdem, Sadi S","year":2024,"journal":"Journal of cardiovascular pharmacology, 83(6), 621-634","doi":"10.1097/FJC.0000000000001564","pmid":"38547520","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07689","title":"Exploring the Therapeutic Potential of Glucagon-Like Peptide 1 (GLP-1) Receptor Agonists in Polycystic Ovary Syndrome.","authors":"Akel, Miis; Ziq, Aya; Kaldas, Paul; Hamden, Jad; Omari, Abdul Rahman; Silanee, Allen","year":2024,"journal":"Cureus, 16(11), e73687","doi":"10.7759/cureus.73687","pmid":"39677183","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07690","title":"The role of dietary fibers in regulating appetite, an overview of mechanisms and weight consequences.","authors":"Akhlaghi, Masoumeh","year":2024,"journal":"Critical reviews in food science and nutrition, 64(10), 3139-3150","doi":"10.1080/10408398.2022.2130160","pmid":"36193993","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07691","title":"GLP-1 derivatives with functional sequences transit and migrate through trigeminal neurons.","authors":"Akita, Tomomi; Shimamura, Mizuki; Tezuka, Ayano; Takagi, Marina; Yamashita, Chikamasa","year":2024,"journal":"European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 195, 114176","doi":"10.1016/j.ejpb.2024.114176","pmid":"38185192","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07692","title":"Outcome on Mesenteric Mass Response of Small-Intestinal Neuroendocrine Tumors Treated by 177Lu-DOTATATE Peptide Receptor Radionuclide Therapy: The MesenLuth Study, a National Study from the French Group of Endocrine Tumors and Endocan-RENATEN Network.","authors":"Al Mansour, Laure; De Mestier, Louis; Haissaguerre, Magalie; Afchain, Pauline; Hadoux, Julien; Lecomte, Thierry; Morland, David; Cottereau, Anne Segolene; De Rycke, Ophelie; Tlili, Ghoufrane; Tordo, Jérémie; Janier, Marc; Deville, Agathe; Walter, Thomas","year":2024,"journal":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 65(2), 258-263","doi":"10.2967/jnumed.123.266063","pmid":"38212066","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07693","title":"Exploring FDA-Approved Frontiers: Insights into Natural and Engineered Peptide Analogues in the GLP-1, GIP, GHRH, CCK, ACTH, and α-MSH Realms.","authors":"Al Musaimi, Othman","year":2024,"journal":"Biomolecules, 14(3)","doi":"10.3390/biom14030264","pmid":"38540684","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07694","title":"Peptide Therapeutics: Unveiling the Potential against Cancer-A Journey through 1989.","authors":"Al Musaimi, Othman","year":2024,"journal":"Cancers, 16(5)","doi":"10.3390/cancers16051032","pmid":"38473389","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07695","title":"Glucagon-like Peptide-1 Receptor Agonists and Diabetic Osteopathy: Another Positive Effect of Incretines? A 12 Months Longitudinal Study.","authors":"Al Refaie, Antonella; Baldassini, Leonardo; Mondillo, Caterina; Ceccarelli, Elena; Tarquini, Roberto; Gennari, Luigi; Gonnelli, Stefano; Caffarelli, Carla","year":2024,"journal":"Calcified tissue international, 115(2), 160-168","doi":"10.1007/s00223-024-01240-1","pmid":"38864922","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"After 12 months of GLP-1RA therapy in 54 T2DM patients (30 on dulaglutide, 24 on semaglutide), bone turnover markers and adiponectin significantly increased while myostatin showed a modest but significant reduction. Lumbar spine BMD by DXA decreased significantly, though the decrease by REMS was not significant. Trabecular bone score showed marginal improvement. Femoral BMD showed modest but significant reduction by both DXA and REMS. The authors interpret the combined findings as preservation of bone quality with reactivation of bone turnover.","whyItMatters":"Type 2 diabetes already increases fracture risk, and weight loss — a primary benefit of GLP-1 drugs — can further reduce bone density. With millions of people now taking semaglutide and dulaglutide, understanding their bone effects is critical. This study provides reassurance that bone quality is preserved even as weight drops, though the density reductions warrant attention in patients already at risk for osteoporosis.","specificNumbers":"","methodology":"This was a 12-month prospective longitudinal study of 65 patients with type 2 diabetes starting GLP-1RA therapy (54 completed the study). Bone mineral density was measured by both DXA and REMS techniques at the lumbar spine and femoral neck. Trabecular bone score, bone turnover markers, adiponectin, and myostatin were assessed at baseline and 12 months.","limitations":"The study had a relatively small sample size (54 completers) with no control group, making it impossible to separate GLP-1RA effects from weight loss effects. The 12-month follow-up may be too short to detect fracture outcomes. The two drugs (dulaglutide and semaglutide) were not directly compared. There was no randomization, and the single-center design limits generalizability."},{"rthcId":"RPEP-07696","title":"Traumatic Brain Injury Induces Nociceptin/Orphanin FQ and Nociceptin Opioid Peptide Receptor Expression within 24 Hours.","authors":"Al Yacoub, Omar N; Zhang, Yong; Patankar, Panini S; Standifer, Kelly M","year":2024,"journal":"International journal of molecular sciences, 25(3)","doi":"10.3390/ijms25031658","pmid":"38338936","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07697","title":"Case reports: Could sexual dysfunction in women with migraine be a side effect of CGRP inhibition?","authors":"Al-Hassany, Linda; Boucherie, Deirdre M; Couturier, Emile G M; MaassenVanDenBrink, Antoinette","year":2024,"journal":"Cephalalgia : an international journal of headache, 44(5), 3331024241248837","doi":"10.1177/03331024241248837","pmid":"38796855","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07698","title":"Nucleic acid-based vaccine for ovarian cancer cells; bench to bedside.","authors":"Al-Hawary, Sulieman Ibraheem Shelash; Jasim, Saade Abdalkareem; Hjazi, Ahmed; Oghenemaro, Enwa Felix; Kaur, Irwanjot; Kumar, Abhinav; Al-Ani, Ahmed Muzahem; Alwaily, Enas R; Redhee, Ahmed Huseen; Mustafa, Yasser Fakri","year":2024,"journal":"Cell biochemistry and function, 42(2), e3978","doi":"10.1002/cbf.3978","pmid":"38515237","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07699","title":"Hypersensitivity to CGRP as a predictive biomarker of migraine prevention with erenumab.","authors":"Al-Khazali, Haidar M; Ashina, Håkan; Christensen, Rune Häckert; Wiggers, Astrid; Rose, Kathrine; Iljazi, Afrim; Amin, Faisal Mohammad; Ashina, Messoud; Snellman, Josefin; Maio-Twofoot, Tina; Schytz, Henrik W","year":2024,"journal":"Cephalalgia : an international journal of headache, 44(6), 3331024241258734","doi":"10.1177/03331024241258734","pmid":"38859744","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07700","title":"Budget impact analysis for three glucagon-like peptide-1 receptor agonist-based therapies for type 2 diabetes mellitus management in Saudi Arabia.","authors":"Al-Omar, Hussain A; Almodaimegh, Hind S; Omaer, Abubker; Alzubaidi, Lamya M; Al-Harbi, Bandar; Al-Harbi, Ibtisam; Hassan, Mohamed; Akhtar, Omar","year":2024,"journal":"Journal of medical economics, 27(1), 418-429","doi":"10.1080/13696998.2024.2319458","pmid":"38420695","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07701","title":"Outcomes of Semaglutide Use in Achieving Target Body Mass Index Before Renal Transplant in Five End-Stage Renal Disease Patients: A Case Series.","authors":"Al-Saad, Naeem; Suhagiya, Gaurang Hasmukhbhai; Shah, Badar Ud Din; Malik, Jahanzeb; Zaidi, Syed Muhammad Jawad","year":2024,"journal":"Cureus, 16(10), e71511","doi":"10.7759/cureus.71511","pmid":"39553100","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07702","title":"Effect of Dual Glucagon-Like Peptide 1/Glucose-Dependent Insulinotropic Polypeptide Receptor Agonist (Tirzepatide) versus Bariatric Surgery on Weight Loss and Nonalcoholic Fatty Liver Disease.","authors":"Al-Sabah, Salman; Al-Khairi, Irina; Jamal, Mohammad; Qaddoumi, Mohammad; Alajmi, Fahad; Kumar, Jijin; Abukhalaf, Nermeen; Cherian, Preethi; Madhu, Dhanya; Arefanian, Hossein; Dsouza, Carol; Alam-Eldin, Nada; AlSabagh, Abdullah; Al Madhoun, Ashraf; Al-Sabah, Suleiman; Al-Mulla, Fahd; Abu-Farha, Mohamed; Abubaker, Jehad","year":2024,"journal":"Medical principles and practice : international journal of the Kuwait University, Health Science Centre, 33(5), 478-490","doi":"10.1159/000540534","pmid":"39047721","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07703","title":"Tirzepatide outcompetes long-acting insulin in managing type 2 diabetes: a meta-analysis of three phase 3 randomized controlled trials.","authors":"Ala, Moein; Mohammad Jafari, Razieh; Dehpour, Ahmad Reza; Poursalehian, Mohammad","year":2024,"journal":"International journal of obesity (2005), 48(12), 1684-1695","doi":"10.1038/s41366-024-01621-4","pmid":"39210008","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07704","title":"Developments in targeting calcitonin gene-related peptide.","authors":"Alabbad, Sawsan; Figueredo, Nathalia; Yuan, Hsiangkuo; Silberstein, Stephen","year":2024,"journal":"Expert review of neurotherapeutics, 24(5), 477-485","doi":"10.1080/14737175.2024.2332754","pmid":"38557226","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07705","title":"Obesity surgery and neural correlates of human eating behaviour: A systematic review of functional MRI studies.","authors":"Alabdulkader, Shahd; Al-Alsheikh, Alhanouf S; Miras, Alexander D; Goldstone, Anthony P","year":2024,"journal":"NeuroImage. Clinical, 41, 103563","doi":"10.1016/j.nicl.2024.103563","pmid":"38237270","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07706","title":"Effect of Semaglutide in Individuals With Obesity or Overweight Without Diabetes.","authors":"Alanazi, Mokhlef; Alshahrani, Jaber Abdullah; Sulayman Aljaberi, Ahmed; Alqahtani, Basel Ali A; Muammer, Mahdi","year":2024,"journal":"Cureus, 16(8), e67889","doi":"10.7759/cureus.67889","pmid":"39328692","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07707","title":"In silico and in vivo experiment of soymilk peptide (tetrapeptide - FFYY) for the treatment of hypertension.","authors":"Alauddin, Md; Amin, Md Ruhul; Siddiquee, Muhammad Ali; Hiwatashi, Kazuyuki; Shimakage, Atsushi; Takahashi, Saori; Shinbo, Mamoru; Komai, Michio; Shirakawa, Hitoshi","year":2024,"journal":"Peptides, 175, 171170","doi":"10.1016/j.peptides.2024.171170","pmid":"38342309","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07708","title":"Safety and Efficacy of Peptide Receptor Radionuclide Therapy (PRRT) Following Bland Embolization for Metastatic Neuroendocrine Tumors.","authors":"Alayli, Adam; Ngo, Hoang; Sikaria, Dhiraj; Ahmed, Altan; Salloum, Elias; Strosberg, Jonathan R; Al-Toubah, Taymeyah E; Kis, Bela; Haider, Mintallah; El-Haddad, Ghassan","year":2024,"journal":"Cancers, 16(15)","doi":"10.3390/cancers16152703","pmid":"39123431","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07709","title":"The Effect of Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists on the Lipid Profile of Diabetic Patients Using Statins: A Retrospective Cohort Study in the Diabetic Center of King Salman Bin Abdulaziz Hospital, Saudi Arabia.","authors":"Albahli, Odai M; Ali, Saqib; Alblaihi, Fahad; Aljaman, Abdulaziz A","year":2024,"journal":"Cureus, 16(7), e65521","doi":"10.7759/cureus.65521","pmid":"39188504","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07710","title":"Long-Term Treatment with the Calcitonin Gene-Related Peptide Receptor Antagonist Erenumab in CADASIL: Two Case Reports.","authors":"Albanese, Maria; Pescini, Francesca; Di Bonaventura, Chiara; Iannone, Luigi Francesco; Bianchi, Silvia; Poggesi, Anna; Bengala, Mario; Mercuri, Nicola Biagio; De Cesaris, Francesco","year":2024,"journal":"Journal of clinical medicine, 13(7)","doi":"10.3390/jcm13071870","pmid":"38610637","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07711","title":"Efficacy and Safety of Injectable Dulaglutide 1.5 mg Among Type 2 Diabetes Patients in Clinics at King Saud Medical City, Riyadh, Saudi Arabia.","authors":"Albargawi, Mashael Saad; Alharbi, Rawan Naser; Alajlani, Mohammad Abbas; Abdulaal, Ibtihal Abdulwarith; Aldakhil, Lina Othman","year":2024,"journal":"Journal of epidemiology and global health, 14(3), 720-729","doi":"10.1007/s44197-024-00207-7","pmid":"38753098","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In this cohort of 205 patients, dulaglutide 1.5 mg weekly produced significant improvements in multiple outcomes at both 6 and 12 months compared to baseline. Weight, BMI, HbA1c, and fasting blood sugar all improved significantly.\n\nThe patient population was notable for the severity and duration of their disease: approximately 33% had diabetes for more than 20 years and 41.4% had class III (severe) obesity. Despite this challenging patient profile, dulaglutide delivered meaningful glycemic and weight benefits. Side effects were predominantly gastrointestinal, with nausea (52%) and fatigue (28%) being the most commonly reported.","whyItMatters":"Most clinical trials of GLP-1 receptor agonists are conducted in Western populations, so real-world data from Middle Eastern populations is valuable for understanding how these drugs perform across different ethnicities, diets, and healthcare settings. Saudi Arabia has one of the highest diabetes prevalence rates globally, making effective treatment data from this population particularly relevant to regional clinical practice.","specificNumbers":"","methodology":"This was a retrospective single-arm cohort study conducted at endocrine and diabetic outpatient clinics at King Saud Medical City in Riyadh. Researchers used purposive sampling to recruit 205 type 2 diabetes patients on dulaglutide. Data were collected from medical records and through phone-based interview questionnaires. Outcomes were assessed at baseline, 6 months, and 12 months of therapy.","limitations":"This was a retrospective, single-arm study without a control group, so improvements cannot be definitively attributed to dulaglutide versus other concurrent treatments or lifestyle changes. Purposive (non-random) sampling may introduce selection bias. Data relied partly on phone interviews, which are subject to recall bias. The study was conducted at a single center in Riyadh, limiting generalizability even within Saudi Arabia. Specific numerical changes in HbA1c, weight, and other measures were not provided in the abstract."},{"rthcId":"RPEP-07712","title":"Scoliidines: Neuroprotective Peptides in Solitary Scoliid Wasp Venoms.","authors":"Alberto-Silva, Carlos; Vieira Portaro, Fernanda Calheta; Kodama, Roberto Tadashi; Gomes, Lais; da Silva, Brenda Rufino; da Cunha E Silva, Felipe Assumpção; Nihei, Ken-Ichi; Konno, Katsuhiro","year":2024,"journal":"Toxins, 16(10)","doi":"10.3390/toxins16100446","pmid":"39453222","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07713","title":"Substance P and Neurokinin-1 receptor are overexpressed in adamantinomatous craniopharyngioma than in the pituitary gland.","authors":"Alcaide, Carlos; Perez, Francisco; Esteban, Francisco; Muñoz, Miguel","year":2024,"journal":"Pituitary, 28(1), 5","doi":"10.1007/s11102-024-01490-0","pmid":"39724307","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Substance P and NK-1R were overexpressed in all 43 human adamantinomatous craniopharyngioma (ACP) samples compared to healthy pituitary gland tissue. This is reported for the first time in this tumor type.\n\nSubstance P expression was widespread throughout the tumor and preferentially localized in the nucleus rather than the cytoplasm of tumor cells. Areas of glial reaction and endothelial cells also expressed SP, primarily in cell nuclei.\n\nNK-1R was expressed mainly in the glial reaction zone, particularly in the nuclei and membranes of inflammatory cells, and in endothelial cells and fibroblasts of tumor blood vessels. Notably, tumor cells themselves did not show significant NK-1R expression, suggesting the peptide-receptor signaling operates primarily through the tumor microenvironment rather than directly on tumor cells.","whyItMatters":"Craniopharyngiomas are difficult to treat — surgery and radiation near the optic nerves and hypothalamus frequently cause devastating side effects including vision loss and hormonal dysfunction. NK-1R antagonist drugs already exist and have been tested in preclinical cancer trials. Finding that SP/NK-1R are overexpressed in these tumors opens the possibility of a less invasive, drug-based treatment approach that could spare patients from the severe sequelae of current therapies.","specificNumbers":"","methodology":"The researchers used immunohistochemistry to examine the expression and distribution of Substance P and NK-1R in 43 human adamantinomatous craniopharyngioma tissue samples, comparing them to healthy pituitary gland samples. They analyzed the cellular localization (nucleus, cytoplasm, membrane) across different cell types within the tumor microenvironment.","limitations":"This is an observational immunohistochemistry study showing expression patterns, not a functional study demonstrating that blocking SP/NK-1R would actually slow tumor growth. The sample size of 43 tumors is reasonable for a rare tumor but still limited. The study does not include quantitative expression data or survival correlations. The healthy pituitary comparison may not perfectly match the developmental origin of craniopharyngiomas. No NK-1R antagonist treatment was tested."},{"rthcId":"RPEP-07714","title":"Glucagon-like Peptide-1 Receptor Agonists Associated Gastrointestinal Adverse Events: A Cross-Sectional Analysis of the National Institutes of Health All of Us Cohort.","authors":"Aldhaleei, Wafa Ali; Abegaz, Tadesse M; Bhagavathula, Akshaya Srikanth","year":2024,"journal":"Pharmaceuticals (Basel, Switzerland), 17(2)","doi":"10.3390/ph17020199","pmid":"38399414","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07715","title":"Beyond Glycemic Control: GLP-1 Receptor Agonists and Their Impact on Calcium Homeostasis in Real-World Patients.","authors":"Alenezi, Bandar T; Elfezzani, Nadra; Uddin, Rukhsana; Patel, Hinali; Chester, Sydney; Abdelmaksoud, Ahmed; Hussein, Mohammad H; Zaitone, Sawsan A; Fawzy, Manal S; Aiash, Hani; Toraih, Eman A","year":2024,"journal":"Journal of clinical medicine, 13(16)","doi":"10.3390/jcm13164896","pmid":"39201039","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 receptor agonists reduced the risk of hypocalcemia by 51% (2.7% vs 5.5%, RR 0.49) but doubled the risk of hypercalcemia (2.3% vs 1.1%, RR 2.02) compared to matched controls. Tirzepatide showed the strongest effects, reducing hypocalcemia by 63% while increasing hypercalcemia by 85%. GLP-1 RA use was also associated with significantly reduced emergency visits (RR 0.57), hospitalizations (RR 0.40), cardiovascular events, and all-cause mortality (HR 0.27). The hypocalcemia-protective effect was most pronounced in the first 6 months.","whyItMatters":"With millions of patients now taking GLP-1 drugs, understanding their full physiological impact is critical. This study reveals a previously poorly understood effect on calcium balance — protecting against low calcium while potentially raising it too high. This has important implications for patients with bone disorders, those on calcium supplements, or those at risk for hypercalcemia. The broader finding of dramatically reduced mortality and hospitalizations further supports these peptide drugs' wide-ranging benefits.","specificNumbers":"n=31,310 (15,655 per group) · hypocalcemia RR 0.49 · hypercalcemia RR 2.02 · emergency visits RR 0.57 · hospitalizations RR 0.40 · mortality HR 0.27 · tirzepatide: 63% hypocalcemia reduction, 85% hypercalcemia increase","methodology":"Retrospective cohort study using the TriNetX Global Collaborative Network. 15,655 adults prescribed GLP-1R agonists were propensity-matched to 15,655 controls. Outcomes included hypocalcemia, hypercalcemia, emergency visits, hospitalizations, cardiovascular events, and all-cause mortality. Individual agent effects (tirzepatide, semaglutide, dulaglutide, liraglutide) were analyzed separately.","limitations":"As a retrospective observational study, causal relationships cannot be established. Propensity matching may not account for all confounding variables. The mechanism behind the calcium effects is not elucidated. The TriNetX database relies on diagnostic codes, which may not capture mild or subclinical calcium disturbances. The study did not assess bone mineral density or fracture risk."},{"rthcId":"RPEP-07716","title":"Pancreatitis with use of new diabetic medications: a real-world data study using the post-marketing FDA adverse event reporting system (FAERS) database.","authors":"Alenzi, Khalidah A; Alsuhaibani, Deemah; Batarfi, Bader; Alshammari, Thamir M","year":2024,"journal":"Frontiers in pharmacology, 15, 1364110","doi":"10.3389/fphar.2024.1364110","pmid":"38860168","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07717","title":"The effectiveness of 0.5 mg and 1mg of semaglutide in patients with type two diabetes and predictors of response: a retrospective cohort study.","authors":"Alenzi, Sara; Alzahrani, Abdullah; Aljaloud, Afnan; Alanazi, Kamayel; Alarfaj, Sumaiah J","year":2024,"journal":"Frontiers in endocrinology, 15, 1395651","doi":"10.3389/fendo.2024.1395651","pmid":"39205685","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07718","title":"Metabolomic Effects of Liraglutide Therapy on the Plasma Metabolomic Profile of Patients with Obesity.","authors":"Alfadda, Assim A; Abdel Rahman, Anas M; Benabdelkamel, Hicham; AlMalki, Reem; Alsuwayni, Bashayr; Alhossan, Abdulaziz; Aldhwayan, Madhawi M; Abdeen, Ghalia N; Miras, Alexander Dimitri; Masood, Afshan","year":2024,"journal":"Metabolites, 14(9)","doi":"10.3390/metabo14090500","pmid":"39330507","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07719","title":"GLP-1 single, dual, and triple receptor agonists for treating type 2 diabetes and obesity: a narrative review.","authors":"Alfaris, Nasreen; Waldrop, Stephanie; Johnson, Veronica; Boaventura, Brunna; Kendrick, Karla; Stanford, Fatima Cody","year":2024,"journal":"EClinicalMedicine, 75, 102782","doi":"10.1016/j.eclinm.2024.102782","pmid":"39281096","tags":["glp-1","tirzepatide","retatrutide"],"studyType":"review","evidenceStrength":"high","keyFinding":"GLP-1 receptor agonists have evolved from single-target drugs into dual and triple receptor agonists that represent the cutting edge of metabolic therapy. Single GLP-1RAs (semaglutide, liraglutide) effectively lower HbA1c, reduce weight, protect against cardiovascular events, and improve kidney health. Dual agonists like tirzepatide (GLP-1/GIP) produce even greater weight loss and glucose control by activating two incretin pathways simultaneously.\n\nThe next frontier is triple agonists — like retatrutide (GLP-1/GIP/glucagon) — which add glucagon receptor activation to increase energy expenditure and fat burning on top of appetite suppression and glucose control. These multi-agonist peptides represent the future direction of incretin-based therapy for both type 2 diabetes and obesity.","whyItMatters":"This 2024 review captures a pivotal moment in metabolic medicine: the transition from effective single-target GLP-1 drugs to dramatically more powerful multi-agonist peptides. With obesity affecting over 650 million adults globally and type 2 diabetes over 460 million, the progression from single → dual → triple agonists offers progressively greater therapeutic power for conditions that drive cardiovascular disease, kidney failure, and premature death.","specificNumbers":"Single, dual, and triple agonists compared · GLP-1, GIP, and glucagon receptors targeted · HbA1c reduction + weight loss + CV protection · Multiple FDA-approved formulations reviewed","methodology":"Narrative review of currently approved GLP-1 receptor agonists and emerging dual (GLP-1/GIP) and triple (GLP-1/GIP/glucagon) agonists for type 2 diabetes and obesity. Covers mechanisms of action, clinical efficacy, routes of administration, and future directions. NIH-funded research.","limitations":"Narrative review without systematic methodology. The abstract does not provide specific efficacy numbers for individual agents. Some dual and triple agonists discussed are still in clinical development and may not achieve approval. The review may not cover all safety concerns equally across the different agent classes."},{"rthcId":"RPEP-07720","title":"Mechanisms of Non-alcoholic Fatty Liver Disease and Beneficial Effects of Semaglutide: A Review.","authors":"Alfawaz, Sultan; Burzangi, Abdulhadi; Esmat, Ahmed","year":2024,"journal":"Cureus, 16(8), e67080","doi":"10.7759/cureus.67080","pmid":"39286709","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review establishes that NAFLD progresses through steatosis (fat accumulation) to non-alcoholic steatohepatitis (NASH, with inflammation/fibrosis) to cirrhosis and hepatocellular carcinoma. NAFLD is both a consequence and contributor to metabolic syndrome. No pharmacological agents are currently approved for NAFLD or NASH. Semaglutide's glycemic control and weight loss properties position it as a promising candidate, with evidence suggesting benefits for individuals with NAFLD through multiple metabolic pathways.","whyItMatters":"NAFLD affects an estimated 25-30% of the global population — over 2 billion people — and the lack of approved treatments represents one of the largest unmet needs in hepatology. With NASH expected to become the leading indication for liver transplant, finding effective treatments is urgent. Semaglutide's phase 2 trial results for NASH (showing histological improvement) have generated significant excitement, and this review contextualizes that potential within the disease biology.","specificNumbers":"","methodology":"Narrative review of published literature examining the pathophysiology of NAFLD and the potential therapeutic effects of semaglutide on fatty liver disease.","limitations":"Published in Cureus (a less selective journal), the review provides a broad overview but may lack the depth and critical analysis of reviews in specialized hepatology journals. The abstract provides no specific data on semaglutide's efficacy in NAFLD. The rapid evolution of the field means the review may not capture the latest clinical trial results. The review was published before resmetirom became the first FDA-approved NASH treatment in 2024, so the claim of 'no authorized agents' has since changed."},{"rthcId":"RPEP-07721","title":"Bridging the Gap Between Diabetes and Cardiovascular Disease: A Comparative Review of Different Glucagon-Like Peptide-1 (GLP-1) Agonists: Efficacy, Safety, and Patient Outcomes.","authors":"Alghamdi, Feras A; Alshegifi, Hussein A; Alhuthayli, Reema S; Helal, Turki; Huwait, Turki A; Alharbi, Turki; Akbar, Abdulrahman F; Alshehri, Wejdan; AlSheikh, Sultan M","year":2024,"journal":"Cureus, 16(11), e74345","doi":"10.7759/cureus.74345","pmid":"39720384","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07722","title":"Anti-inflammatory role of glucagon-like peptide 1 receptor agonists and its clinical implications.","authors":"Alharbi, Saleh Hadi","year":2024,"journal":"Therapeutic advances in endocrinology and metabolism, 15, 20420188231222367","doi":"10.1177/20420188231222367","pmid":"38288136","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07723","title":"Incretin hormone agonists: Current and emerging pharmacotherapy for obesity management.","authors":"Alhomoud, Ibrahim S; Talasaz, Azita H; Chandrasekaran, Preethi; Brown, Roy; Mehta, Anurag; Dixon, Dave L","year":2024,"journal":"Pharmacotherapy, 44(9), 738-752","doi":"10.1002/phar.4607","pmid":"39225417","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Current incretin hormone agonists — liraglutide (SCALE trials), semaglutide (STEP trials), and tirzepatide (SURMOUNT-1) — have demonstrated remarkable efficacy in promoting weight loss and improving metabolic outcomes for obesity. The next generation of obesity drugs in development includes oral GLP-1 receptor agonists, triple agonists targeting GLP-1/GIP/glucagon receptors simultaneously, GLP-1/glucagon receptor co-agonists, oral GIP/GLP-1 co-agonists, and combinations of long-acting amylin receptor agonists with GLP-1 receptor agonists.","whyItMatters":"With over 800 million people affected by obesity worldwide and traditional lifestyle interventions often producing insufficient or unsustainable weight loss, incretin-based therapies represent the most significant pharmacological advance in obesity management in decades. This review maps the current and emerging landscape, helping clinicians and patients understand what's available now and what's coming next.","specificNumbers":"","methodology":"Narrative review synthesizing data from key clinical trial programs — SCALE (liraglutide), STEP (semaglutide), and SURMOUNT (tirzepatide) — along with the emerging pipeline of dual and triple incretin agonists. Therapies are categorized by mechanism of action and route of administration.","limitations":"As a narrative review, the article does not use systematic search methodology. Specific weight loss percentages and adverse event data from the named clinical trials are not detailed in the abstract. The emerging therapies discussed are at various stages of development and may not all reach market approval. Long-term (multi-year) safety and weight maintenance data for newer agents remain limited."},{"rthcId":"RPEP-07724","title":"Biological activities, Peptidomics and in silico analysis of low-fat Cheddar cheese after in vitro digestion: Impact of blending camel and bovine Milk.","authors":"Ali, Abdelmoneim H; Öztürk, Hale İnci; Eylem, Cemil Can; Nemutlu, Emirhan; Tarique, Mohammad; Subhash, Athira; Liu, Shao-Quan; Kamal-Eldin, Afaf; Ayyash, Mutamed","year":2024,"journal":"Food chemistry, 460(Pt 3), 140760","doi":"10.1016/j.foodchem.2024.140760","pmid":"39137574","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07725","title":"Glucagon-like peptide-1 analogues in monogenic syndromic obesity: Real-world data from a large cohort of Alström syndrome patients.","authors":"Ali, Sadaf; Baig, Shanat; Wanninayake, Subadra; da Silva Xavier, Gabriela; Dawson, Charlotte; Paisey, Richard; Geberhiwot, Tarekegn","year":2024,"journal":"Diabetes, obesity & metabolism, 26(3), 989-996","doi":"10.1111/dom.15398","pmid":"38151964","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07726","title":"Semaglutide for the management of diabesity: The real-world experience.","authors":"Alkhalifah, Mohammed; Afsar, Hafsa; Shams, Anindya; Blaibel, Dania; Chandrabalan, Vishnu; Pappachan, Joseph M","year":2024,"journal":"World journal of methodology, 14(3), 91832","doi":"10.5662/wjm.v14.i3.91832","pmid":"39310241","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide treatment produced significant real-world improvements across all key diabesity outcomes. Mean body weight decreased from 110.4 kg at baseline to 99.9 kg at 12 months and 96.8 kg at latest follow-up (approximately 13.6 kg total loss). HbA1c improved from 82 mmol/mol at baseline to 67 mmol/mol at 12 months and 71 mmol/mol at latest follow-up.\n\nInsulin requirements also decreased, with mean daily doses dropping from 95 units at baseline to 76.5 units at latest follow-up — a roughly 20% reduction. Side effects were mild and primarily gastrointestinal, improving with continued use.","whyItMatters":"Clinical trials often include carefully selected patients who may not represent the broader population. This real-world study confirms that semaglutide's benefits translate to typical clinical practice, where patients have longer diabetes histories, multiple comorbidities, and varying adherence. The sustained weight loss and blood sugar improvement over 2.6 years is particularly encouraging for a condition that often worsens over time.","specificNumbers":"","methodology":"This was a retrospective real-world study at a large US academic hospital. Researchers reviewed electronic medical records of 106 patients with type 2 diabetes and obesity who were prescribed semaglutide between January 2019 and May 2023. They tracked weight, HbA1c, insulin dose adjustments, and side effects at 6 months, 12 months, and at the latest available follow-up. Mean treatment duration was 2.6 years.","limitations":"This is a retrospective, single-center, observational study without a control group, so improvements cannot be definitively attributed to semaglutide alone. The sample size of 106 patients is modest. There may be selection bias in which patients were prescribed semaglutide. HbA1c appeared to slightly worsen from 12 months to latest follow-up (67 to 71 mmol/mol), which could indicate diminishing effect over time. Adherence data was not reported. The study did not assess cardiovascular or renal outcomes."},{"rthcId":"RPEP-07727","title":"Poly-Agonist Pharmacotherapies for Metabolic Diseases: Hopes and New Challenges.","authors":"Allard, Camille; Cota, Daniela; Quarta, Carmelo","year":2024,"journal":"Drugs, 84(2), 127-148","doi":"10.1007/s40265-023-01982-6","pmid":"38127286","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07728","title":"Efficacy of Angiotensin Receptor-Neprilysin Inhibitor and Its Renal Outcome in Heart Failure Patients: A Systematic Review of Randomized Clinical Trials.","authors":"Almansouri, Naiela E; Bakkannavar, Saloni; Faheem, Youmna; Jaiswal, Amisha; Shergill, Kainaat; Boppana, Kusalik; Nath, Tuheen Sankar","year":2024,"journal":"Cureus, 16(2), e54501","doi":"10.7759/cureus.54501","pmid":"38516430","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across large-scale RCTs involving 17,327 participants with an average follow-up of ~2.9 years, sacubitril/valsartan compared to ACE inhibitors and ARBs showed:\n\n- Notable reduction in NT-proBNP levels (a peptide biomarker of heart failure severity)\n- Prevention of further deterioration in renal function\n- Decreased hospitalizations for heart failure\n- No increased risk of cardiovascular mortality\n- Benefits observed across different types of heart failure and regardless of renal status","whyItMatters":"Heart failure is a leading cause of hospitalization and death worldwide. Sacubitril/valsartan works through a unique mechanism — by boosting natriuretic peptide levels through neprilysin inhibition — representing a fundamentally new approach to heart failure treatment. The additional kidney protection is particularly important since many heart failure patients also have kidney disease.","specificNumbers":"","methodology":"Systematic review of randomized controlled trials identified through PubMed, PMC, and Google Scholar. Large-scale RCTs comparing sacubitril/valsartan to ACE inhibitors or ARBs in heart failure patients were analyzed. Efficacy outcomes included cardiovascular death, heart failure hospitalization rates, and NT-proBNP changes. Renal outcome was assessed as impairment of renal function.","limitations":"The systematic review did not include a formal meta-analysis with pooled statistics. The search was limited to three databases. Individual trial populations varied in heart failure type, severity, and comorbidities, which may affect comparability. Long-term data beyond the average 2.9-year follow-up is limited. The review focused on comparison with ACEi/ARB but didn't compare to newer agents like SGLT2 inhibitors."},{"rthcId":"RPEP-07729","title":"Impact of Erenumab on Migraine Disability: A Three-Month MIDAS (Migraine Disability Assessment Scale) Score Analysis at Dubai Health Facilities.","authors":"Almarzooqi, Ali; Zidan, Marwan","year":2024,"journal":"Cureus, 16(8), e67113","doi":"10.7759/cureus.67113","pmid":"39156992","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"After three months of erenumab treatment, the 26 migraine patients showed a median decrease of 13 points on the MIDAS disability scale. No statistically significant differences were found between genders or between erenumab dosage groups, but trends toward improvement were observed in all subgroups. The lack of statistical significance is attributed to the small sample size and absence of a control group.","whyItMatters":"CGRP-targeting drugs like erenumab have transformed migraine treatment, but most evidence comes from Western populations. This study adds real-world data from a Middle Eastern healthcare setting, supporting erenumab's effectiveness in reducing migraine disability across different patient demographics.","specificNumbers":"","methodology":"Retrospective analysis of 26 patients diagnosed with migraine at Dubai Health facilities. All received erenumab for three months. MIDAS (Migraine Disability Assessment Scale) scores were measured at baseline and after treatment. Non-parametric statistical tests compared outcomes across gender and dosage subgroups.","limitations":"Very small sample size (n=26) limits statistical power. No control group, so improvement cannot be definitively attributed to erenumab versus natural fluctuation or placebo effect. Retrospective design introduces potential biases. Three months is a relatively short follow-up period. Published in Cureus, which has a less rigorous peer review process than top-tier journals."},{"rthcId":"RPEP-07730","title":"Cross-sectional, case-control and longitudinal associations between exposure to glucagon-like peptide-1 receptor agonists and the dispensing of antidepressants.","authors":"Almeida, Osvaldo P; Fong, Zheng; Hill Almeida, Lydia M; Sanfilippo, Frank M; Page, Amy; Etherton-Beer, Christopher","year":2024,"journal":"Diabetes, obesity & metabolism, 26(7), 2925-2932","doi":"10.1111/dom.15616","pmid":"38650544","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07731","title":"Effectiveness and Safety of GLP-1 Receptor Agonists in Patients with Type 1 Diabetes.","authors":"Almohareb, Sumaya N; Alfayez, Osamah M; Aljuaid, Shoroq S; Alshahrani, Walaa A; Bakhsh, Ghalia; Alshammari, Mohammed K; Al Yami, Majed S; Alshaya, Omar A; Alomran, Abdullah S; Korayem, Ghazwa B; Almohammed, Omar A","year":2024,"journal":"Journal of clinical medicine, 13(21)","doi":"10.3390/jcm13216532","pmid":"39518671","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07732","title":"Radiolabeled peptides and their expanding role in clinical imaging and targeted cancer therapy.","authors":"Aloj, Luigi; Mansi, Rosalba; De Luca, Stefania; Accardo, Antonella; Tesauro, Diego; Morelli, Giancarlo","year":2024,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 30(10), e3607","doi":"10.1002/psc.3607","pmid":"38710638","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07733","title":"Dynamic fluctuations of salivary CGRP levels during migraine attacks: association with clinical variables and phenotypic characterization.","authors":"Alpuente, Alicia; Gallardo, Victor J; Asskour, Laila; Caronna, Edoardo; Torres-Ferrus, Marta; Pozo-Rosich, Patricia","year":2024,"journal":"The journal of headache and pain, 25(1), 58","doi":"10.1186/s10194-024-01772-9","pmid":"38637736","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07734","title":"Practical guide: Glucagon-like peptide-1 and dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonists in diabetes mellitus.","authors":"Alqifari, Saleh Fahad; Alkomi, Omar; Esmail, Abdullah; Alkhawami, Khadijeh; Yousri, Shahd; Muqresh, Mohamad Ayham; Alharbi, Nawwarah; Khojah, Abdullah A; Aljabri, Ahmed; Allahham, Abdulrahman; Prabahar, Kousalya; Alshareef, Hanan; Aldhaeefi, Mohammed; Alrasheed, Tariq; Alrabiah, Ali; AlBishi, Laila A","year":2024,"journal":"World journal of diabetes, 15(3), 331-347","doi":"10.4239/wjd.v15.i3.331","pmid":"38591071","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07735","title":"Safety and Efficacy of Atogepant for the Preventive Treatment of Migraines in Adults: A Systematic Review and Meta-Analysis.","authors":"Alrasheed, Abdulrahim Saleh; Almaqboul, Taif Mansour; Alshamrani, Reem Ali; AlMohish, Noor Mohammad; Alabdali, Majed Mohammad","year":2024,"journal":"Journal of clinical medicine, 13(22)","doi":"10.3390/jcm13226713","pmid":"39597856","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07736","title":"Liraglutide Effect on Weight and A1C in Patients with Type 2 Diabetes Mellitus: Real-World Data from a Single Tertiary Care Center in Saudi Arabia.","authors":"AlRashidi, Awadh; AlArfaj, Rasha; Al Ruqaib, Abdullah; Masuadi, Emad; AlFaraj, Munirah; Al-Saleh, Yousef; AlEnezi, Rakan; Mahzari, Moeber M; Aljulifi, Mohammed Z","year":2024,"journal":"Journal of pharmacy & bioallied sciences, 16(Suppl 4), S3108-S3112","doi":"10.4103/jpbs.jpbs_473_24","pmid":"39926854","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07737","title":"Analyzing the morphology and avian β-defensins genes (AvβD) expression in the small intestine of Cobb500 broiler chicks fed with sodium butyrate.","authors":"Alsafy, Mohamed A M; Abdellatif, Islam A; El-Gendy, Samir A A; Abumandour, Mohamed M A; Noreldin, Ahmed; Bassuoni, Naglaa F","year":2024,"journal":"BMC veterinary research, 20(1), 434","doi":"10.1186/s12917-024-04253-y","pmid":"39342153","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07738","title":"NY-ESO-1 antigen: A promising frontier in cancer immunotherapy.","authors":"Alsalloum, Alaa; Shevchenko, Julia A; Sennikov, Sergey","year":2024,"journal":"Clinical and translational medicine, 14(9), e70020","doi":"10.1002/ctm2.70020","pmid":"39275923","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"NY-ESO-1 serves a dual role as both a tumor-associated antigen and its own adjuvant, potentially functioning as a damage-associated molecular pattern. It elicits strong humoral immune responses with antibody frequencies correlating with disease progression. Multiple therapeutic approaches have shown promise: peptide/protein vaccines, DNA/mRNA vaccines, bacterial and viral vector delivery, dendritic cell vaccines, artificial adjuvant vector cells, and TCR-engineered T cells. Next-generation NY-ESO-1 T-cell products and integration with lymph node-targeted vaccines are addressing current efficacy challenges.","whyItMatters":"Cancer immunotherapy needs targets that are broadly expressed in tumors but absent in normal tissues. NY-ESO-1 fits this profile exceptionally well and triggers natural immune responses, making it one of the most studied and promising targets for developing personalized cancer treatments that could work across multiple cancer types.","specificNumbers":"","methodology":"This was a comprehensive narrative review analyzing published literature on NY-ESO-1 immunogenicity, vaccine strategies, and adoptive T-cell therapies across multiple cancer types and clinical trial phases.","limitations":"As a review, it synthesizes existing research rather than generating new data. Many of the therapeutic approaches discussed are still in clinical trials and have not yet demonstrated definitive survival benefits in large randomized studies. Tumor heterogeneity — not all cancer cells express NY-ESO-1 — remains a challenge for single-antigen targeting strategies."},{"rthcId":"RPEP-07739","title":"Liraglutide's Effect on Weight Management in Subjects With Pre-diabetes: A Systematic Review & Meta-Analysis.","authors":"Alsanea, Sary; Alkofide, Hadeel; Almadi, Bana; Almohammed, Omar; Alwhaibi, Abdulrahman; Alrabiah, Ziyad; Kalagi, Nora","year":2024,"journal":"Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists, 30(8), 737-745","doi":"10.1016/j.eprac.2024.05.009","pmid":"38782201","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07740","title":"Sex, race, and BMI in clinical trials of medications for obesity over the past three decades: a systematic review.","authors":"Alsaqaaby, Moath S; Cooney, Sarah; le Roux, Carel W; Pournaras, Dimitri J","year":2024,"journal":"The lancet. Diabetes & endocrinology, 12(6), 414-421","doi":"10.1016/S2213-8587(24)00098-6","pmid":"38723646","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07741","title":"Cost-effectiveness analysis of once-weekly semaglutide vs. once-daily liraglutide administered subcutaneously in patients with overweight and obesity: a decision analysis.","authors":"Alshahawey, M; Ghazy, M; El Morshedy, M; El Said, N O","year":2024,"journal":"European review for medical and pharmacological sciences, 28(9), 3365-3374","doi":"10.26355/eurrev_202405_36181","pmid":"38766793","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07742","title":"Did Primary Healthcare Patients in Riyadh Experience Their First Migraine Episodes After a Stressful Event, and What Triggers and Relievers Do They Commonly Report?","authors":"Alsuwayt, Saleh S; Aljaied, Yasser S; Ahmed, Amani A; Al Hussain, Fatimah A; Alawami, Hawra M; Alamer, Zahra B; Aljasser, Deema A; Dirani, Maria A; Alshanqiti, Waad A; Bin Kanan, Hissah M; Jamous, Shaimaa T; Alabrazi, Nawal A","year":2024,"journal":"Cureus, 16(11), e74712","doi":"10.7759/cureus.74712","pmid":"39735073","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07743","title":"Snake and arthropod venoms: Search for inflammatory activity in human cells involved in joint diseases.","authors":"Alvarez-Flores, Miryam Paola; Correia Batista, Isabel de Fatima; Villas Boas, Isadora Maria; Bufalo, Michelle Cristiane; de Souza, Jean Gabriel; Oliveira, Douglas Souza; Bonfá, Giuliano; Fernandes, Cristina Maria; Marques Porto, Rafael; Lichtenstein, Flavio; Picolo, Gisele; Tambourgi, Denise V; Chudzinski-Tavassi, Ana Marisa; Ibañez, Olga Célia Martinez; Teixeira, Catarina","year":2024,"journal":"Toxicon : official journal of the International Society on Toxinology, 238, 107568","doi":"10.1016/j.toxicon.2023.107568","pmid":"38110040","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"At non-cytotoxic concentrations, most of the 21 tested venoms activated inflammatory mediator release: IL-6, IL-8, and TNF-α from chondrocytes, synoviocytes, and macrophages, and substance P from neuron-like cells. Viperidae snake venoms were more inflammatory than Elapidae venoms, and arthropod venoms were generally less inflammatory than snake venoms.\n\nNotably, some venoms induced IL-10 (anti-inflammatory) release from macrophages. The scorpion Buthus occitanus venom was unique — it induced IL-10 release without increasing inflammatory cytokine production from macrophages, making it the most promising candidate for anti-inflammatory drug discovery. The platform also measured neuropeptide release (substance P and β-endorphin) from differentiated sensory neuron-like cells, connecting venom effects to pain modulation pathways.","whyItMatters":"Inflammatory joint diseases affect hundreds of millions of people worldwide, and current treatments often fail to achieve remission. Animal venoms contain thousands of bioactive peptides and proteins optimized by evolution, but their effects on joint-specific cells had never been systematically studied. This screening platform identifies which venoms — and eventually which specific compounds within them — have the best therapeutic potential, focusing research efforts on the most promising candidates like the Buthus occitanus scorpion venom.","specificNumbers":"","methodology":"Twenty-one venoms from snake and arthropod species across different taxonomic families and geographic origins were tested. A cell-based assay platform was established using human chondrocytes, synoviocytes, THP1 macrophages, and differentiated sensory neuron-like cells. Cells were stimulated with venoms at non-cytotoxic concentrations for 24 hours. Cytokine release (IL-6, IL-8, TNF-α, IL-1β, IL-10) and neuropeptide release (substance P, β-endorphin) were measured.","limitations":"This is an in vitro screening study — no animal or human therapeutic testing was performed. The study tested whole venoms, not individual peptide or protein components, so the specific bioactive molecules responsible for the observed effects are unknown. The 24-hour exposure period may not reflect chronic inflammatory disease conditions. Cell lines and primary cells in culture may not fully replicate the complex joint microenvironment. The non-cytotoxic concentrations used may differ from therapeutically relevant doses."},{"rthcId":"RPEP-07744","title":"Effect of fasting-induced headache on calcitonin gene related peptide (CGRP) and other clinical biomarkers on the first day of Ramadan: Sub-analysis from a randomized open label clinical trial.","authors":"Alwhaibi, Abdulrahman; Alasmari, Fawaz; Almutairi, Faris; Assiri, Mohammed A; Aldawsari, Feras S; Aloyayd, Saud T; Alhejji, Abdullah A; Alotaibi, Jawaher A; Albilali, Abdulrazaq; Almohammed, Omar A; Alsanea, Sary","year":2024,"journal":"The journal of headache and pain, 25(1), 181","doi":"10.1186/s10194-024-01886-0","pmid":"39415097","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07745","title":"Voltammetric detection of Neuropeptide Y using a modified sawhorse waveform.","authors":"Alyamni, Nadiah; Abot, Jandro L; Zestos, Alexander G","year":2024,"journal":"Analytical and bioanalytical chemistry, 416(21), 4807-4818","doi":"10.1007/s00216-024-05373-y","pmid":"38914733","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07746","title":"Changes in ghrelin, GLP-1, and PYY levels after diet and exercise in obese individuals.","authors":"Alyar, Gülşah; Umudum, Fatma Zuhal; Akbaş, Nergis","year":2024,"journal":"Revista da Associacao Medica Brasileira (1992), 70(1), e20230263","doi":"10.1590/1806-9282.20230263","pmid":"38511748","tags":[],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"After 12 weeks of combined diet (1,000–1,500 kcal/day) and exercise (at least 5,000 steps/day), obese individuals showed significant changes in appetite-regulating peptide hormones: ghrelin (the hunger hormone) decreased significantly, while PYY (a satiety hormone) increased significantly. These shifts support better appetite control and weight maintenance.\n\nHowever, even after the intervention, the obese group's GLP-1 and PYY levels still did not reach the levels seen in healthy-weight controls. This suggests that while diet and exercise improve appetite hormone signaling, they may not fully normalize the peptide imbalances associated with obesity.","whyItMatters":"Understanding how diet and exercise affect appetite peptides helps explain why these interventions work — and why they sometimes aren't enough. The finding that GLP-1 and PYY didn't normalize even after treatment provides biological context for why many people struggle to maintain weight loss, and why GLP-1 agonist drugs like semaglutide have become so popular: they may compensate for a deficit that lifestyle changes alone can't fully correct.","specificNumbers":"n=62 obese participants + 48 healthy controls · 12-week intervention · 1,000–1,500 kcal/day diet · ≥5,000 steps/day exercise · BMI ≥30 for case group","methodology":"Researchers enrolled 62 obese individuals (BMI ≥30) and 48 healthy-weight controls. The obese group followed a 12-week program combining a calorie-restricted diet (1,000–1,500 kcal/day, tailored to age, gender, and BMI) with daily exercise (at least 5,000 steps/day). Blood samples were taken before and after the 12-week period, and ghrelin, GLP-1, and PYY levels were measured using ELISA assays.","limitations":"The study used a relatively modest exercise target (5,000 steps/day, which is below most health recommendations). The abstract doesn't report the actual amount of weight lost, making it harder to connect the hormone changes to specific outcomes. There was no randomization or blinding described, and the control group didn't undergo the intervention, limiting causal conclusions. The ELISA methodology may also be less precise than newer assay techniques."},{"rthcId":"RPEP-07747","title":"Intraarterial Administration of Peptide Receptor Radionuclide Therapy in Patients with Advanced Meningioma: Initial Safety and Efficacy.","authors":"Amerein, Adriana; Maurer, Christoph; Kircher, Malte; Gäble, Alexander; Krebold, Anne; Rinscheid, Andreas; Viering, Oliver; Pfob, Christian H; Bundschuh, Ralph A; Behrens, Lars; Braat, Arthur Jat; Berlis, Ansgar; Lapa, Constantin","year":2024,"journal":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 65(12), 1911-1916","doi":"10.2967/jnumed.124.268217","pmid":"39448269","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07748","title":"Humanin-G Ameliorates Hemorrhage-Induced Acute Lung Injury in Mice Through AMPKα1-Dependent and -Independent Mechanisms.","authors":"Amman, Allison M; Wolfe, Vivian; Piraino, Giovanna; Ziady, Assem; Zingarelli, Basilia","year":2024,"journal":"Biomedicines, 12(11)","doi":"10.3390/biomedicines12112615","pmid":"39595179","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Humanin-G produced several protective effects after hemorrhagic shock:\n\n• Ameliorated histological lung damage in all groups — male and female, regardless of AMPKα1 status\n• Reduced lung neutrophil infiltration in male and female AMPKα1 wild-type mice only — not in knockouts, indicating this effect requires AMPKα1\n• Improved mean arterial blood pressure in male AMPKα1 knockout mice\n• Activated AMPKα in lung tissue (cytosolic and nuclear) in wild-type mice\n• Did not modify STAT3 activation\n\nKey sex differences emerged: male wild-type mice had more pronounced neutrophil infiltration than females, and male AMPKα1 knockout mice experienced significant blood pressure declines after resuscitation compared to male wild-types. Hemorrhagic shock downregulated AMPKα1/α2 catalytic subunits in wild-type mice.","whyItMatters":"Acute lung injury after hemorrhagic shock is a leading cause of death in trauma patients, and there are no specific pharmacological treatments for it. Humanin-G's ability to protect lung tissue through multiple mechanisms — some dependent on AMPK and others not — suggests it could provide broad protection even in patients whose AMPK activity has declined with age. The sex-dependent findings are also clinically important, as men and women may need different treatment approaches.","specificNumbers":"","methodology":"Male and female AMPKα1 wild-type and knockout mice (8-13 months old, mimicking adult human patients) underwent hemorrhagic shock by controlled blood withdrawal, followed by resuscitation with their own shed blood plus lactated Ringer's solution. Mice were treated with PEGylated humanin-G or vehicle (control). Three hours after resuscitation, lungs were assessed histologically for injury scores, neutrophil infiltration, and molecular markers including AMPKα1/α2 subunits, STAT3, and other signaling proteins via western blot and other analyses.","limitations":"This is an animal study with a 3-hour post-resuscitation endpoint, which may not capture longer-term lung recovery or late-onset injury. The abstract does not specify the number of mice per group. The hemorrhagic shock model, while clinically relevant, involves controlled blood withdrawal that may not fully replicate the uncontrolled hemorrhage seen in trauma patients. PEGylated humanin-G was used (for longer half-life), and results may differ from native humanin. The 8-13 month mouse age range introduces variability."},{"rthcId":"RPEP-07749","title":"Genetic variants associated with response to anti-CGRP monoclonal antibody therapy in a chronic migraine Han Chinese population.","authors":"An, Yu-Chin; Hung, Kuo-Sheng; Liang, Chih-Sung; Tsai, Chia-Kuang; Tsai, Chia-Lin; Chen, Sy-Jou; Lin, Yu-Kai; Lin, Guan-Yu; Yeh, Po-Kuan; Yang, Fu-Chi","year":2024,"journal":"The journal of headache and pain, 25(1), 149","doi":"10.1186/s10194-024-01850-y","pmid":"39266962","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07750","title":"Beyond the venom: Exploring the antimicrobial peptides from Androctonus species of scorpion.","authors":"Anandhan Sujatha, Vinutha; Gopalakrishnan, Chandrasekhar; Anbarasu, Amarnath; Ponnusamy, Chandra Sekar; Choudhary, Rajkumar; Saravanan Geetha, Sree Agash; Ramalingam, Rajasekaran","year":2024,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 30(11), e3613","doi":"10.1002/psc.3613","pmid":"38749486","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07751","title":"Investigation of imaging the somatostatin receptor by opening the blood-brain barrier with melittin - A feasibility study using positron emission tomography and [64Cu]Cu-DOTATATE.","authors":"Andersen, Ida Vang; Bidesi, Natasha Shalina Rajani; Shalgunov, Vladimir; Jørgensen, Jesper Tranekjær; Gustavsson, Tobias; Strømgaard, Kristian; Ingemann Jensen, Andreas T; Kjær, Andreas; Herth, Matthias M","year":2024,"journal":"Nuclear medicine and biology, 132-133, 108905","doi":"10.1016/j.nucmedbio.2024.108905","pmid":"38555651","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07752","title":"Successful liver transplantation as rescue therapy in a patient with metastases from a vasoactive intestinal peptide producing neuroendocrine tumor.","authors":"Andreassen, Mikkel; Garbyal, Rajendra Singh; Larsen, Peter Nørgaard; Hansen, Carsten Palnæs; Hannibal, Jens; Oturai, Peter; Knigge, Ulrich; Schultz, Nicolai","year":2024,"journal":"Journal of surgical case reports, 2024(5), rjae371","doi":"10.1093/jscr/rjae371","pmid":"38826856","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07753","title":"Pre-prandial plasma liver-expressed antimicrobial peptide 2 (LEAP2) concentration in humans is inversely associated with hunger sensation in a ghrelin independent manner.","authors":"Andreoli, María F; Fittipaldi, Antonela S; Castrogiovanni, Daniel; De Francesco, Pablo N; Valdivia, Spring; Heredia, Florencia; Ribet-Travers, Carole; Mendez, Ignacio; Fasano, María V; Schioth, Helgi B; Doi, Suhail A; Habib, Abdella M; Perello, Mario","year":2024,"journal":"European journal of nutrition, 63(3), 751-762","doi":"10.1007/s00394-023-03304-8","pmid":"38157050","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07754","title":"The Antimicrobial Activity of Human Defensins at Physiological Non-Permeabilizing Concentrations Is Caused by the Inhibition of the Plasma Membrane H+-ATPases.","authors":"Andrés, María T; Fierro, Patricia; Antuña, Victoria; Fierro, José F","year":2024,"journal":"International journal of molecular sciences, 25(13)","doi":"10.3390/ijms25137335","pmid":"39000442","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07755","title":"The Archetypal Gamma-Core Motif of Antimicrobial Cys-Rich Peptides Inhibits H+-ATPases in Target Pathogens.","authors":"Andrés, María T; Yount, Nannette Y; Acosta-Zaldívar, Maikel; Yeaman, Michael R; Fierro, José F","year":2024,"journal":"International journal of molecular sciences, 25(17)","doi":"10.3390/ijms25179672","pmid":"39273619","tags":["antimicrobial-peptides","host-defense"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Researchers discovered that the gamma-core motif — an ancient structural element found in many cysteine-rich antimicrobial peptides across different species — kills microbes by inhibiting their cell membrane H+-ATPase pumps. Peptides containing this motif from six phylogenetically diverse sources (human lactoferrin, plus peptides from insects, plants, and fungi) all shared the same killing mechanism.\n\nThe common features included: cell death without breaking the membrane apart, loss of intracellular potassium through specific channels, dependence on cellular respiration, involvement of mitochondrial ATP synthase, and increases in intracellular ATP. These findings suggest the gamma-core motif is an ancient, universal antimicrobial weapon that has been conserved across kingdoms of life for billions of years.","whyItMatters":"Antimicrobial resistance is one of the biggest threats to global health, and antimicrobial peptides (AMPs) are promising alternatives to conventional antibiotics. Understanding exactly how AMPs kill pathogens is essential for designing better ones. This study reveals that a single structural motif — the gamma-core — is the key antimicrobial element shared across diverse natural defense peptides from humans to plants to insects. This means nature has converged on the same solution independently many times, suggesting it's a particularly effective and hard-to-resist antimicrobial strategy.","specificNumbers":"6 phylogenetically diverse peptides tested (hLf, afnA, SolyC, PA1b, PvD1, thanatin) · all share gamma-core motif · common mechanism: H+-ATPase inhibition · cell death without membrane lysis · K+ efflux via Tok1p channels in yeast · mitochondrial ATP synthase involvement confirmed","methodology":"The researchers tested peptides containing the gamma-core motif from six different organisms for antimicrobial activity. Mechanistic studies used yeast (Candida) as a model organism to examine membrane integrity, potassium ion flux, respiration dependence, mitochondrial ATP synthase involvement, and intracellular ATP levels. Comparisons were made to BM2, a known fungal membrane H+-ATPase inhibitor, to confirm the target.","limitations":"All experiments were conducted in vitro, primarily in yeast (Candida). Whether the H+-ATPase inhibition mechanism operates identically in bacteria and other fungi requires further validation. The study demonstrates a shared mechanism across multiple peptides but does not resolve the complete atomic-level interaction between the gamma-core motif and H+-ATPases. In vivo antimicrobial efficacy of gamma-core peptides was not tested."},{"rthcId":"RPEP-07756","title":"Incidence of new onset type 2 diabetes in adults living with obesity treated with tirzepatide or semaglutide: real world evidence from an international retrospective cohort study.","authors":"Anson, Matthew; Henney, Alex E; Broadwell, Nicholas; Zhao, Sizheng S; Ibarburu, Gema H; Lip, Gregory Y H; Wilding, John P H; Cuthbertson, Daniel J; Alam, Uazman","year":2024,"journal":"EClinicalMedicine, 75, 102777","doi":"10.1016/j.eclinm.2024.102777","pmid":"39246719","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07757","title":"Risk of Anaphylaxis Among New Users of GLP-1 Receptor Agonists: A Cohort Study.","authors":"Anthony, Mary S; Aroda, Vanita R; Parlett, Lauren E; Djebarri, Leila; Berreghis, Sofia; Calingaert, Brian; Beachler, Daniel C; Crowe, Christopher L; Johannes, Catherine B; Juhaeri, Juhaeri; Lanes, Stephan; Pan, Chunshen; Rothman, Kenneth J; Saltus, Catherine W; Walsh, Kathleen E","year":2024,"journal":"Diabetes care, 47(4), 712-719","doi":"10.2337/dc23-1911","pmid":"38363873","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07758","title":"Exploring Liraglutide in Lithium-Pilocarpine-Induced Temporal Lobe Epilepsy Model in Rats: Impact on Inflammation, Mitochondrial Function, and Behavior.","authors":"Antmen, Fatma Merve; Fedaioglu, Zeynep; Acar, Dilan; Sayar, Ahmed Kerem; Yavuz, Ilayda Esma; Ada, Ece; Karakose, Bengisu; Rzayeva, Lale; Demircan, Sevcan; Kardouh, Farah; Senay, Simge; Kolgazi, Meltem; Suyen, Guldal; Oz-Arslan, Devrim","year":2024,"journal":"Biomedicines, 12(10)","doi":"10.3390/biomedicines12102205","pmid":"39457518","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 56 Sprague Dawley rats with lithium-pilocarpine-induced status epilepticus: Liraglutide reduced NLRP3 inflammasome pathway activation (↓NLRP3, Caspase-1, IL-1β) in hippocampal tissue. It activated the Nrf2 antioxidant pathway (↑Nrf-2, p-Nrf-2). Mitochondrial dynamics proteins were restored (Pink1, Mfn2, Drp1 normalized). Mitochondrial function in peripheral blood mononuclear cells was altered in both healthy and epileptic rats. Behavioral testing (open field, elevated plus maze, Morris water maze) showed liraglutide reversed the movement-enhancing effect of epilepsy.","whyItMatters":"About one-third of epilepsy patients don't respond to current anti-seizure medications. Epilepsy is increasingly understood as not just a seizure disorder but a neuroinflammatory and metabolic disease — with mitochondrial dysfunction playing a central role. Liraglutide targets all three problems simultaneously (inflammation, oxidative stress, mitochondrial dysfunction), making it a compelling candidate for a disease-modifying epilepsy treatment rather than just a seizure suppressor.","specificNumbers":"","methodology":"Fifty-six male Sprague Dawley rats were divided into groups. Temporal lobe epilepsy was induced via low-dose repeated lithium chloride-pilocarpine injections causing status epilepticus. Liraglutide or vehicle was administered. Hippocampal tissue was analyzed by Western blot for inflammatory markers (NLRP3, Caspase-1, IL-1β), antioxidant pathways (Nrf-2, p-Nrf-2), and mitochondrial dynamics proteins (Pink1, Mfn2, Drp1). Peripheral blood mononuclear cell mitochondrial function was assessed by flow cytometry. Behavior was evaluated using open field, elevated plus maze, and Morris water maze tests.","limitations":"Rat model of chemically induced epilepsy may not perfectly replicate human TLE, which develops over years. The study assessed markers of inflammation and mitochondrial dynamics but did not directly measure seizure frequency or severity reduction. The behavioral improvements were in non-epileptic behaviors (locomotion, anxiety) rather than seizure outcomes. Short treatment duration may not reflect long-term neuroprotection. Liraglutide doses in rats may not translate directly to human dosing. The specific contribution of GLP-1 receptor activation in brain versus peripheral effects was not separated."},{"rthcId":"RPEP-07759","title":"Molecular insights into the inhibition of angiotensin-converting enzyme 1 by hemopressin peptides.","authors":"Antony, Priya; Baby, Bincy; Rahma, Aaesha; Samad, Shamaa Abdul; Dhaheri, Yusra Al; Vijayan, Ranjit","year":2024,"journal":"Scientific reports, 14(1), 28726","doi":"10.1038/s41598-024-78893-3","pmid":"39567621","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07760","title":"Filling the data gap on CGRP mAb therapy in low- to middle-income countries in Southeast Asia: insights from a real-world study in Thailand.","authors":"Anukoolwittaya, Prakit; Hiransuthikul, Akarin; Pongpitakmetha, Thanakit; Thanprasertsuk, Sekh; Rattanawong, Wanakorn","year":2024,"journal":"The journal of headache and pain, 25(1), 150","doi":"10.1186/s10194-024-01859-3","pmid":"39267011","tags":["cgrp","clinical-outcomes"],"studyType":"observational","evidenceStrength":"preliminary","keyFinding":"In the first real-world study of CGRP monoclonal antibody therapy from Thailand, 47 migraine patients (mostly using galcanezumab) showed strong responses over 6 months. At the 6-month mark, 89% had at least a 30% reduction in monthly migraine days, 71.6% achieved at least 50% reduction, and 58.5% achieved at least 70% reduction.\n\nMonthly headache days decreased significantly over time (adjusted β = -0.42, p<0.001) and disability scores (MIDAS) also dropped significantly (adjusted β = -1.12, p=0.003). The response patterns were similar between patients with episodic migraine and chronic migraine, though episodic migraine patients had slightly higher response rates overall. Chronic migraine patients showed a steeper improvement trend in reducing abortive medication use.","whyItMatters":"Nearly all real-world data on CGRP antibodies for migraine comes from wealthy nations. This study fills an important gap by demonstrating that these peptide-targeting therapies work effectively in a Southeast Asian population — a region where migraine treatment options and clinical data have been limited. This matters for expanding access and informing treatment decisions in low- and middle-income countries where most of the world's migraine sufferers live.","specificNumbers":"n=47 · 85.1% female · median age 37.2 years · 70.2% on galcanezumab · 89% achieved ≥30% MHD reduction at 6 months · 71.6% achieved ≥50% · 58.5% achieved ≥70% · p<0.001 for MHD decrease · p=0.003 for MIDAS improvement","methodology":"This was a single-center retrospective chart review at a Thai medical center. Researchers reviewed records of 47 migraine patients who started CGRP monoclonal antibody therapy (70.2% galcanezumab) and tracked outcomes over 6 months. They measured monthly headache days, disability scores (MIDAS), and abortive medication use. Response rates were calculated at standard thresholds (30%, 50%, 70% reduction), and trends were compared between episodic and chronic migraine patients using adjusted regression models.","limitations":"The sample size of 47 is small, limiting statistical power for subgroup comparisons. As a single-center retrospective study, it is subject to selection bias and lacks a control group. The Thai population studied may not represent all Southeast Asian populations. Six months of follow-up is relatively short for assessing long-term efficacy and durability of response."},{"rthcId":"RPEP-07761","title":"Metabolic effects of very-low calorie diet, Semaglutide, or combination of the two, in individuals with type 2 diabetes mellitus.","authors":"Anyiam, Oluwaseun; Phillips, Bethan; Quinn, Katie; Wilkinson, Daniel; Smith, Kenneth; Atherton, Philip; Idris, Iskandar","year":2024,"journal":"Clinical nutrition (Edinburgh, Scotland), 43(8), 1907-1913","doi":"10.1016/j.clnu.2024.06.034","pmid":"38996661","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07762","title":"Vicious cycle of vitamin B1 insufficiency and heart failure in cardiology outpatients.","authors":"Ao, Misora; Takabayashi, Kensuke; Tomita, Rika; Fujita, Ryoko; Miyawaki, Takashi; Tanaka, Kiyoshi","year":2024,"journal":"Journal of clinical biochemistry and nutrition, 75(3), 241-246","doi":"10.3164/jcbn.24-137","pmid":"39583975","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07763","title":"Cloning and Functional Analysis of Skin Host Defense Peptides from Yakushima Tago's Brown Frog (Rana tagoi yakushimensis) and Development of Serum Endotoxin Detection System.","authors":"Aono, Taichi; Tamura, Saki; Suzuki, Yua; Imanara, Taichi; Niwa, Ryosei; Yamane, Yoshie; Kobayashi, Tetsuya; Kikuyama, Sakae; Hasunuma, Itaru; Iwamuro, Shawichi","year":2024,"journal":"Antibiotics (Basel, Switzerland), 13(12)","doi":"10.3390/antibiotics13121127","pmid":"39766517","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07764","title":"GLP-1 receptor agonists: A novel pharmacotherapy for binge eating (Binge eating disorder and bulimia nervosa)? A systematic review.","authors":"Aoun, Laurence; Almardini, Shaza; Saliba, Fares; Haddadin, Fadi; Mourad, Omar; Jdaidani, Jennifer; Morcos, Zeina; Al Saidi, Ibrahim; Bou Sanayeh, Elie; Saliba, Saliba; Almardini, Michel; Zaidan, Julie","year":2024,"journal":"Journal of clinical & translational endocrinology, 35, 100333","doi":"10.1016/j.jcte.2024.100333","pmid":"38449772","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07765","title":"Effects of weight loss from oral semaglutide administration on cardiometabolic risk factors in Japanese patients with type 2 diabetes: a retrospective analysis using propensity score matching.","authors":"Aoyama, Kazuki; Nakajima, Yuya; Meguro, Shu; Hayashi, Kaori","year":2024,"journal":"Diabetology international, 15(4), 794-805","doi":"10.1007/s13340-024-00744-3","pmid":"39469553","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07766","title":"THE EFFECT OF INTRANASAL ADMINISTRATION OF BIOLOGICALLY ACTIVE SUBSTANCES OF AMINO ACID AND PEPTIDE NATURE ON THE MONOAMINE SYSTEMS OF THE BRAIN.","authors":"Apryatin, S; Moiseenko, V; Gainetdinov, R; Apryatina, V","year":2024,"journal":"Georgian medical news, 55-67","doi":null,"pmid":"39724881","tags":[],"studyType":"Review","evidenceStrength":"preliminary","keyFinding":"Intranasal delivery of amino acid and peptide-based compounds can effectively reach the brain's monoamine systems (dopamine, serotonin, norepinephrine) by bypassing the blood-brain barrier through the nose-to-brain pathway. This review synthesizes experimental evidence showing that nasally administered peptides can modulate neurotransmitter systems relevant to psychiatric and neurodegenerative diseases.\n\nThe nose-to-brain route exploits direct neural connections (primarily the olfactory and trigeminal nerves) to transport peptide drugs from the nasal cavity to the central nervous system, avoiding both the blood-brain barrier and first-pass liver metabolism. The approach shows promise for conditions including schizophrenia, depression, anxiety, ADHD, Alzheimer's disease, and Parkinson's disease.","whyItMatters":"Most peptide drugs cannot cross the blood-brain barrier, which has been the biggest obstacle to using peptides for brain diseases. Intranasal delivery offers a non-invasive workaround that could unlock peptide therapies for millions of people with psychiatric and neurodegenerative conditions. The growing burden of these diseases worldwide makes finding effective brain-targeted delivery methods increasingly urgent.","specificNumbers":"Nose-to-brain pathway bypasses BBB + liver · Targets: dopamine, serotonin, norepinephrine systems · Potential applications: schizophrenia, depression, anxiety, ADHD, Alzheimer's, Parkinson's","methodology":"Narrative review of experimental studies on intranasal delivery of amino acid and peptide compounds to the brain, focusing on transport mechanisms via the nose-to-brain projection and therapeutic efficacy on monoamine neurotransmitter systems. Published in Georgian Medical News.","limitations":"Published in Georgian Medical News, a lower-impact journal. The abstract is quite general and doesn't provide specific data on any individual peptide or clinical outcome. Most evidence discussed is likely preclinical (animal studies). The review doesn't address key practical challenges like nasal irritation, dose consistency, or regulatory hurdles for intranasal peptide products."},{"rthcId":"RPEP-07767","title":"Health-promoting peptides in fermented beverages.","authors":"Apud, Gisselle Raquel; Kristof, Irina; Ledesma, Silvana Cecilia; Stivala, Maria Gilda; Aredes Fernandez, Pedro Adrian","year":2024,"journal":"Revista Argentina de microbiologia, 56(3), 336-345","doi":"10.1016/j.ram.2024.02.003","pmid":"38599912","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07768","title":"The combination of a glucagon-like peptide-1 and amylin receptor agonists reduces alcohol consumption in both male and female rats.","authors":"Aranäs, Cajsa; Edvardsson, Christian E; Zentveld, Lindsay; Vallöf, Daniel; Witley, Sarah; Tufvesson-Alm, Maximilian; Shevchouk, Olesya T; Vestlund, Jesper; Jerlhag, Elisabet","year":2024,"journal":"Acta neuropsychiatrica, 37, e42","doi":"10.1017/neu.2024.58","pmid":"39639536","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Adding salmon calcitonin (sCT, amylin receptor agonist) to ongoing dulaglutide (GLP-1R agonist) treatment reduced alcohol intake in both male and female rats without tolerance development. When sCT and dulaglutide were started simultaneously, an initial reduction in alcohol intake was observed in both sexes, but tolerance developed over time. Both treatment combinations consistently decreased food consumption and body weight in males and females. The treatment combination did not affect inflammatory mediators or receptor gene expression but did change fat tissue morphology.","whyItMatters":"Alcohol use disorder (AUD) is a leading cause of preventable death with limited treatment options. The growing anecdotal and clinical evidence that GLP-1 drugs reduce alcohol cravings has generated enormous interest. This study takes the logical next step — combining two gut-brain peptide pathways (GLP-1 and amylin) to potentially enhance the anti-alcohol effect. The finding that treatment sequencing matters is practically important for clinical trial design.","specificNumbers":"","methodology":"Two separate alcohol-drinking experiments in rats of both sexes. Experiment 1: sCT was added to ongoing dulaglutide treatment (sequential approach). Experiment 2: sCT and dulaglutide were initiated simultaneously (concurrent approach). Outcomes measured included alcohol intake, food consumption, body weight, inflammatory mediators, amylin and GLP-1 receptor gene expression, and fat tissue morphology.","limitations":"Rat alcohol-drinking models may not fully replicate human AUD patterns and motivations. Tolerance development with simultaneous treatment is concerning and would need to be addressed before clinical use. The study did not include a mechanistic analysis of why sequential addition worked better than simultaneous treatment. Specific dose-response relationships were not explored. The alcohol reduction effect was not compared to either drug alone as a single agent. Fat tissue morphology changes were observed but their significance is unclear."},{"rthcId":"RPEP-07769","title":"Design of peptide therapeutics as protein-protein interaction inhibitors to treat neurodegenerative diseases.","authors":"Ariawan, Daryl; Thananthirige, Kanishka P M; El-Omar, Ali; van der Hoven, Julia; Genoud, Sian; Stefen, Holly; Fath, Thomas; van Eersel, Janet; Ittner, Lars M; Tietz, Ole","year":2024,"journal":"RSC advances, 14(47), 34637-34642","doi":"10.1039/d4ra05040a","pmid":"39479480","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Researchers deconstructed the peptide drug nerinetide — a neuroprotective agent for stroke and Alzheimer's disease — to understand the relationship between its plasma stability, ability to enter neurons, and therapeutic efficacy. Nerinetide combines a cell-penetrating peptide (CPP) sequence for neuronal delivery with a protein-protein interaction (PPI) inhibitory sequence that blocks harmful protein complex formation. The study provides design guidelines for creating next-generation peptide PPI inhibitors for neurodegenerative diseases.","whyItMatters":"Neurodegenerative diseases like Alzheimer's and stroke have limited treatment options, and many disease-driving processes involve protein-protein interactions that are difficult to block with conventional drugs. Nerinetide represents a proof-of-concept that peptides can both penetrate brain cells and disrupt harmful protein interactions. Understanding the design principles behind its success could accelerate development of a new class of neuroprotective peptide drugs.","specificNumbers":"Nerinetide sequence deconstructed · CPP + PPI inhibitor design · plasma stability, neuronal delivery, and efficacy relationships characterized · design guidelines established","methodology":"The researchers systematically deconstructed the nerinetide peptide sequence to study each functional component — the cell-penetrating portion and the protein-protein interaction inhibitory portion. They evaluated plasma stability, intraneuronal delivery efficiency, and drug efficacy for various sequence modifications to establish structure-activity relationships and design principles for future peptide therapeutics.","limitations":"The abstract provides limited detail on specific experimental results and quantitative measurements. The study appears focused on structure-activity relationships rather than in vivo disease model testing. The translation from design guidelines to actual therapeutic candidates for neurodegenerative diseases requires further development and testing."},{"rthcId":"RPEP-07770","title":"Exploring the Potential Impact of GLP-1 Receptor Agonists on Substance Use, Compulsive Behavior, and Libido: Insights from Social Media Using a Mixed-Methods Approach.","authors":"Arillotta, Davide; Floresta, Giuseppe; Papanti Pelletier, G Duccio; Guirguis, Amira; Corkery, John Martin; Martinotti, Giovanni; Schifano, Fabrizio","year":2024,"journal":"Brain sciences, 14(6)","doi":"10.3390/brainsci14060617","pmid":"38928616","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07771","title":"Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial.","authors":"Aronne, Louis J; Sattar, Naveed; Horn, Deborah B; Bays, Harold E; Wharton, Sean; Lin, Wen-Yuan; Ahmad, Nadia N; Zhang, Shuyu; Liao, Ran; Bunck, Mathijs C; Jouravskaya, Irina; Murphy, Madhumita A","year":2024,"journal":"JAMA, 331(1), 38-48","doi":"10.1001/jama.2023.24945","pmid":"38078870","tags":["glp-1-receptor-agonists"],"studyType":"randomized-controlled-trial","evidenceStrength":"strong","keyFinding":"In the SURMOUNT-4 trial, adults with obesity who continued tirzepatide after an initial 36-week treatment period maintained and extended their weight loss, reaching a total reduction of 25.3% from baseline at 88 weeks. Those who switched to placebo regained most of their lost weight, ending with only 9.9% total weight reduction.\n\nDuring the 36-week open-label lead-in, participants lost an average of 20.9% of their body weight on tirzepatide. After randomization, those who continued treatment lost an additional 5.5%, while those who switched to placebo regained 14.0% from their week-36 weight. A striking 89.5% of participants staying on tirzepatide kept at least 80% of their initial weight loss, compared to just 16.6% in the placebo group.","whyItMatters":"This trial answers a critical question in obesity medicine: what happens when you stop taking tirzepatide? The answer is clear — most of the weight comes back. This has major implications for patients and healthcare systems, because it suggests tirzepatide works best as a long-term or indefinite treatment rather than a short course. The results also demonstrate that continuing treatment doesn't just maintain weight loss but actually deepens it, with participants losing an additional 5.5% beyond what they achieved in the first 36 weeks.","specificNumbers":"n=670 · 20.9% weight loss at 36 weeks · 25.3% total loss with continued treatment at 88 weeks · 9.9% total loss with placebo · 89.5% maintained ≥80% of weight loss on tirzepatide vs 16.6% on placebo · P<.001","methodology":"Phase 3, randomized withdrawal design at 70 sites across 4 countries. Adults with BMI ≥30 (or ≥27 with a weight-related condition) but without diabetes received open-label tirzepatide at the maximum tolerated dose (10 or 15 mg weekly, subcutaneous) for 36 weeks. At week 36, 670 participants were randomized 1:1 to either continue tirzepatide or switch to placebo for an additional 52 weeks (through week 88). Double-blind during the randomized period.","limitations":"The trial excluded people with diabetes, so results may not generalize to that population. The randomized withdrawal design means all participants received tirzepatide initially — there's no pure placebo control from baseline. The study population was mostly women (71%) and the mean age was 48 years. Long-term safety and weight outcomes beyond 88 weeks remain unknown. The trial was industry-sponsored by Eli Lilly."},{"rthcId":"RPEP-07772","title":"Extracellular vesicles from primary human macrophages stimulated with VIP or PACAP mediate anti-SARS-CoV-2 activities in monocytes through NF-κB signaling pathway.","authors":"Arteaga-Blanco, Luis A; Temerozo, Jairo R; Tiné, Lucas P S; Dantas-Pereira, Luíza; Sacramento, Carolina Q; Fintelman-Rodrigues, Natalia; Toja, Beatriz M; Gomes Dias, Suelen Silva; de Freitas, Caroline S; Espírito-Santo, Camila Couto; Silva, Ygor P; Frozza, Rudimar L; Bozza, Patrícia T; Menna-Barreto, Rubem F S; Souza, Thiago Moreno L; Bou-Habib, Dumith Chequer","year":2024,"journal":"Microbes and infection, 26(8), 105400","doi":"10.1016/j.micinf.2024.105400","pmid":"39069117","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Extracellular vesicles (EVs) from VIP- and PACAP-stimulated macrophages produced three key effects in SARS-CoV-2-infected monocytes: (1) inhibited viral RNA synthesis and replication, (2) protected cells from virus-induced cytopathic effects, and (3) reduced production of pro-inflammatory mediators. The anti-inflammatory mechanism worked through prevention of SARS-CoV-2-induced NF-κB activation.\n\nTwo distinct EV subpopulations were identified based on morphology: large EVs (LEV) and small EVs (SEV), both isolated by differential centrifugation from macrophages cultured for 24 hours in serum-reduced conditions. These findings reveal that neuropeptide-stimulated macrophage EVs possess immunoregulatory properties that could contribute to both antiviral and anti-inflammatory responses during COVID-19.","whyItMatters":"The 'cytokine storm' — an excessive inflammatory response driven largely by monocytes — is a major cause of death in severe COVID-19. This study reveals a natural neuropeptide-immune system communication pathway that can simultaneously fight the virus and calm the inflammation. Understanding how VIP and PACAP modulate macrophage signaling through extracellular vesicles could inform new therapeutic strategies for COVID-19 and other inflammatory viral infections.","specificNumbers":"","methodology":"Primary human monocyte-derived macrophages (MDM) were stimulated with the neuropeptides VIP and PACAP. Extracellular vesicles were isolated from culture medium by differential centrifugation and characterized morphologically into large and small EV subpopulations. These EVs were then applied to SARS-CoV-2-infected monocytes. Viral replication was measured by RNA quantification, cell viability by cytopathic effect assessment, inflammatory mediator production by relevant assays, and NF-κB activation by pathway analysis.","limitations":"All experiments were conducted in vitro using primary human cells, not in living patients or animal models. The clinical relevance of these EV-mediated effects during actual COVID-19 infection is unknown. The specific cargo within the EVs responsible for antiviral and anti-inflammatory effects was not identified. Quantitative data on viral inhibition levels were not provided in the abstract. Translation of EV-based therapies to clinical use faces significant manufacturing and delivery challenges."},{"rthcId":"RPEP-07773","title":"In Silico Hydrolysis of Lupin (Lupinus angustifolius L.) Conglutins with Plant Proteases Releases Antihypertensive and Antidiabetic Peptides That Are Bioavailable, Non-Toxic, and Gastrointestinal Digestion Stable.","authors":"Arámburo-Gálvez, Jesús Gilberto; Tinoco-Narez-Gil, Raúl; Mora-Melgem, José Antonio; Sánchez-Cárdenas, Cesar Antonio; Gracia-Valenzuela, Martina Hilda; Flores-Mendoza, Lilian Karem; Figueroa-Salcido, Oscar Gerardo; Ontiveros, Noé","year":2024,"journal":"International journal of molecular sciences, 25(23)","doi":"10.3390/ijms252312866","pmid":"39684577","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07774","title":"Evaluation of Antimicrobial Peptides in Saliva as Potential Therapeutic Agents Against Oral Pathogens in Pakistan.","authors":"Asad, Rabia; Shahzad, Muhammad Asif; Knawal, Sana; Bano, Shaher; Javed, Mariyah; Anwar, Ammara; Shah, Syed Shahab Ud Din","year":2024,"journal":"Cureus, 16(11), e73758","doi":"10.7759/cureus.73758","pmid":"39677072","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07775","title":"Cerebral Artery Vasoconstriction After Galcanezumab Loading Dose for Migraine Prevention: A Case Report.","authors":"Asawavichienjinda, Thanin; Jittapiromsak, Nutchawan; Blumenfeld, Andrew","year":2024,"journal":"Pain and therapy, 13(6), 1705-1712","doi":"10.1007/s40122-024-00665-8","pmid":"39365416","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07776","title":"Lipid-Based Nanoparticle Functionalization with Coiled-Coil Peptides for In Vitro and In Vivo Drug Delivery.","authors":"Aschmann, Dennis; Knol, Renzo A; Kros, Alexander","year":2024,"journal":"Accounts of chemical research, 57(8), 1098-1110","doi":"10.1021/acs.accounts.3c00769","pmid":"38530194","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07777","title":"Conditioned Medium from Human Amniotic Membrane-Derived Mesenchymal Stem Cells Modulates Inflammatory and Myofibrotic Factors in Vivo.","authors":"Asgharnezhad, Gazaleh; Mohamadi, Sachli; Mohseni, Mahdieh Mehrab; Mousvi-Niri, Neda; Naseroleslami, Maryam","year":2024,"journal":"The journal of Tehran Heart Center, 19(3), 198-205","doi":null,"pmid":"40271173","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07778","title":"Multifactor Quality and Safety Analysis of Semaglutide Products Sold by Online Sellers Without a Prescription: Market Surveillance, Content Analysis, and Product Purchase Evaluation Study.","authors":"Ashraf, Amir Reza; Mackey, Tim Ken; Vida, Róbert György; Kulcsár, Győző; Schmidt, János; Balázs, Orsolya; Domián, Bálint Márk; Li, Jiawei; Csákó, Ibolya; Fittler, András","year":2024,"journal":"Journal of medical Internet research, 26, e65440","doi":"10.2196/65440","pmid":"39509151","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07779","title":"Uncovering chikungunya virus-encoded miRNAs and host-specific targeted genes associated with antiviral immune responses: an integrated bioinformatics approach.","authors":"Ashraf, Sajida; Sufyan, Muhammad; Aslam, Bilal; Khalid, Hina; Albekairi, Norah A; Alshammari, Abdulrahman; Alharbi, Metab; Nisar, Muhammad Atif; Khurshid, Mohsin; Ashfaq, Usman Ali","year":2024,"journal":"Scientific reports, 14(1), 18614","doi":"10.1038/s41598-024-67436-5","pmid":"39127786","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07780","title":"The cost-effectiveness analysis of semaglutide for the treatment of adult and adolescent patients with overweight and obesity: a systematic review.","authors":"Asiabar, Ali Sarabi; Rezaei, Mohammad Ali; Jafarzadeh, Dariush; Rajaei, Soheila; Atefimanesh, Pezhman; Soleimanpour, Samira; Meher, Mohammad Hossein Kafaei; Azari, Samad","year":2024,"journal":"European journal of clinical pharmacology, 80(12), 1857-1870","doi":"10.1007/s00228-024-03755-w","pmid":"39254692","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07781","title":"Systemic Factors Affecting Human Beta-Defensins in Oral Cavity.","authors":"Atalay, Nur; Balci, Nur; Gürsoy, Mervi; Gürsoy, Ulvi Kahraman","year":2024,"journal":"Pathogens (Basel, Switzerland), 13(8)","doi":"10.3390/pathogens13080654","pmid":"39204254","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07782","title":"Arginine vasopressin deficiency: diagnosis, management and the relevance of oxytocin deficiency.","authors":"Atila, Cihan; Refardt, Julie; Christ-Crain, Mirjam","year":2024,"journal":"Nature reviews. Endocrinology, 20(8), 487-500","doi":"10.1038/s41574-024-00985-x","pmid":"38693275","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The hypertonic saline test combined with plasma copeptin measurement has emerged as the diagnostic test with the highest accuracy for differentiating causes of polyuria-polydipsia syndrome, replacing the traditional water deprivation test as the gold standard.\n\nDesmopressin, a synthetic AVP analogue specific for the AVP receptor 2 (AVPR2), remains the mainstay treatment and leads to rapid improvements in both excessive urination and excessive thirst. The main risk is dilutional hyponatraemia, which can be mitigated using the 'desmopressin escape method' — a dosing strategy that allows brief periods of breakthrough polyuria.\n\nAdditionally, recent evidence points to a concurrent oxytocin deficiency in patients with AVP deficiency, opening a new avenue for potential therapeutic intervention with oxytocin substitution.","whyItMatters":"This review reflects a major shift in how a relatively common endocrine condition is diagnosed and named. The replacement of the water deprivation test with the copeptin-based hypertonic saline test represents a meaningful improvement in diagnostic accuracy. The recognition of concurrent oxytocin deficiency could lead to new treatment approaches that address symptoms beyond water balance, such as social and emotional well-being.","specificNumbers":"","methodology":"This is a narrative review published in Nature Reviews Endocrinology. The authors synthesized evidence from clinical studies conducted over the past decade on copeptin-based diagnostic tests, desmopressin treatment strategies, and emerging research on oxytocin deficiency in patients with AVP deficiency.","limitations":"As a narrative review, this paper synthesizes existing evidence rather than presenting new original data. The evidence for oxytocin deficiency in AVP-deficient patients is described as preliminary, with the authors themselves noting that feasible clinical tests and interventional trials are still needed. The review does not include a systematic search methodology or meta-analysis of diagnostic test accuracy."},{"rthcId":"RPEP-07783","title":"Dulaglutide reduces oxidative DNA damage and hypermethylation in the somatic cells of mice fed a high-energy diet by restoring redox balance, inflammatory responses, and DNA repair gene expressions.","authors":"Attia, Sabry M; Alshamrani, Ali A; Ahmad, Sheikh F; Albekairi, Norah A; Nadeem, Ahmed; Attia, Mohamed S M; Ansari, Mushtaq A; Almutairi, Faris; Bakheet, Saleh A","year":2024,"journal":"Journal of biochemical and molecular toxicology, 38(7), e23764","doi":"10.1002/jbt.23764","pmid":"38963172","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07784","title":"Dulaglutide rescues the elevated testicular dysfunction in a mouse model of high-fat diet-induced obesity.","authors":"Attia, Sabry M; Alshamrani, Ali A; Ahmad, Sheikh F; Albekairi, Norah A; Nadeem, Ahmed; Attia, Mohamed S M; Ansari, Mushtaq A; Alqahtani, Faleh; Bakheet, Saleh A; Harisa, Gamaleldin I","year":2024,"journal":"Mutation research. Genetic toxicology and environmental mutagenesis, 898, 503805","doi":"10.1016/j.mrgentox.2024.503805","pmid":"39147447","tags":[],"studyType":"animal","evidenceStrength":"low","keyFinding":"Dulaglutide (a GLP-1 receptor agonist) completely restored testicular function in obese mice to normal levels. Obese mice had lower testes-to-body weight ratios, increased sperm DNA damage, chromosomal abnormalities, reduced sperm count and motility, more morphological defects, and disrupted testicular redox balance. Five weeks of dulaglutide treatment reversed all of these parameters back to control levels.\n\nImportantly, dulaglutide showed no harmful effects on testicular cells when given to healthy, non-obese mice, suggesting safety for reproductive function.","whyItMatters":"Obesity is a known cause of male infertility, and millions of men are now taking GLP-1 drugs for weight loss. This study addresses a critical safety and potential benefit question: not only does dulaglutide appear safe for male reproductive function, it may actually reverse the testicular damage caused by obesity itself.","specificNumbers":"0.6 mg/kg/day dulaglutide · 12-week high-fat diet · 5 weeks treatment · All parameters restored to control levels · No harm in healthy mice","methodology":"Mouse study using a high-fat diet-induced obesity model. After 12 weeks on a high-fat diet, obese mice were randomized to receive dulaglutide (0.6 mg/kg/day) or saline for 5 weeks. Healthy mice also received dulaglutide as a safety control. Testes and sperm were collected 24 hours after the last injection. Outcomes included sperm DNA damage (comet assay), chromosomal abnormalities at diakinesis-metaphase I, spermiogram analysis (count, motility, morphology), and testicular redox balance markers.","limitations":"This is a mouse study, and reproductive physiology differs significantly between mice and humans. The dulaglutide dose (0.6 mg/kg/day) is much higher relative to body weight than typical human doses. The 5-week treatment period covers roughly one mouse spermatogenesis cycle but may not reflect long-term effects. Human clinical data on GLP-1 drugs and male fertility are still needed."},{"rthcId":"RPEP-07785","title":"Enhancing peptide and PMO delivery to mouse airway epithelia by chemical conjugation with the amphiphilic peptide S10.","authors":"Auger, Maud; Sorroza-Martinez, Luis; Brahiti, Nadine; Huppé, Carole-Ann; Faucher-Giguère, Laurence; Arbi, Imen; Hervault, Maxime; Cheng, Xue; Gaillet, Bruno; Couture, Frédéric; Guay, David; Soultan, Al-Halifa","year":2024,"journal":"Molecular therapy. Nucleic acids, 35(3), 102290","doi":"10.1016/j.omtn.2024.102290","pmid":"39233851","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07786","title":"Megestrol acetate as an overlooked cause of hyperglycemia in end-stage renal disease: A case of polypharmacy.","authors":"Aurora, John; Zheng, Theresa; Fortunati, Julieta Rossi; Erenler, Feyza","year":2024,"journal":"Journal of the American Pharmacists Association : JAPhA, 64(6), 102248","doi":"10.1016/j.japh.2024.102248","pmid":"39277084","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07787","title":"The efficacy and safety of GLP-1 agonists in PCOS women living with obesity in promoting weight loss and hormonal regulation: A meta-analysis of randomized controlled trials.","authors":"Austregésilo de Athayde De Hollanda Morais, Beatriz; Martins Prizão, Vitória; de Moura de Souza, Mariana; Ximenes Mendes, Beatriz; Rodrigues Defante, Maria Luiza; Cosendey Martins, Otavio; Rodrigues, Adriane Maria","year":2024,"journal":"Journal of diabetes and its complications, 38(10), 108834","doi":"10.1016/j.jdiacomp.2024.108834","pmid":"39178623","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07788","title":"Optimization, physicochemical stability and in vivo study of alginate-chitosan composites as nanocarriers for low molecular weight angiotensin I-converting enzyme (ACE)-inhibitory peptide.","authors":"Auwal, Shehu Muhammad; Ghanisma, Siti Balqis Muhammad; Saari, Nazamid","year":2024,"journal":"Journal of food and drug analysis, 32(3), 358-370","doi":"10.38212/2224-6614.3522","pmid":"39636769","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07789","title":"Comparative efficacy and safety of weekly tirzepatide versus weekly insulin in type 2 diabetes: A network meta-analysis of randomized clinical trials.","authors":"Ayesh, Hazem; Suhail, Sajida; Ayesh, Suhail; Niswender, Kevin","year":2024,"journal":"Diabetes, obesity & metabolism, 26(9), 3801-3809","doi":"10.1111/dom.15725","pmid":"38923379","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07790","title":"Comparative Efficacy and Safety of Weekly GLP-1/GIP Agonists vs. Weekly Insulin in Type 2 Diabetes: A Network Meta-Analysis of Randomized Controlled Trials.","authors":"Ayesh, Hazem; Suhail, Sajida; Ayesh, Suhail; Niswender, Kevin","year":2024,"journal":"Biomedicines, 12(9)","doi":"10.3390/biomedicines12091943","pmid":"39335457","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07791","title":"Comparative efficacy and safety of weekly dulaglutide versus weekly insulin in type 2 diabetes: A network meta-analysis of randomized clinical trials.","authors":"Ayesh, Hazem; Suhail, Sajida; Ayesh, Suhail; Niswender, Kevin","year":2024,"journal":"Metabolism open, 22, 100284","doi":"10.1016/j.metop.2024.100284","pmid":"38699397","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07792","title":"Risk of Esophageal and Gastric Cancer in Patients with Type 2 Diabetes Receiving Glucagon-like Peptide-1 Receptor Agonists (GLP-1 RAs): A National Analysis.","authors":"Ayoub, Mark; Aibani, Rafi; Dodd, Tiana; Ceesay, Muhammed; Bhinder, Muhammad; Faris, Carol; Amin, Nisar; Daglilar, Ebubekir","year":2024,"journal":"Cancers, 16(18)","doi":"10.3390/cancers16183224","pmid":"39335195","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07793","title":"Bioinspired synthetic peptide-based biomaterials regenerate bone through biomimicking of extracellular matrix.","authors":"Azadi, Sareh; Yazdanpanah, Mohammad Ali; Afshari, Ali; Alahdad, Niloofar; Chegeni, Solmaz; Angaji, Abdolhamid; Rezayat, Seyed Mahdi; Tavakol, Shima","year":2024,"journal":"Journal of tissue engineering, 15, 20417314241303818","doi":"10.1177/20417314241303818","pmid":"39670180","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07794","title":"Digital Footprints of Obesity Treatment: GLP-1 Receptor Agonists and the Health Equity Divide.","authors":"Azizi, Zahra; Rodriguez, Fatima; Assimes, Themistocles L","year":2024,"journal":"Circulation, 150(3), 171-173","doi":"10.1161/CIRCULATIONAHA.124.069680","pmid":"39008562","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07795","title":"Efficacy of Tirzepatide Dual GIP/GLP-1 Receptor Agonist In Patients with Idiopathic Intracranial Hypertension. A Real-World Propensity Score-Matched Study.","authors":"Azzam, Ahmed Y; Essibayi, Muhammed Amir; Farkas, Nathan; Azab, Mohammed A; Morsy, Mahmoud M; Elamin, Osman; Elswedy, Adam; Zomia, Ahmed Saad Al; Alotaibi, Hammam A; Alamoud, Ahmed; Atallah, Oday; Abukhadijah, Hana J; Dmytriw, Adam A; Baker, Amanda; Khatri, Deepak; Haranhalli, Neil; Altschul, David J","year":2024,"journal":"medRxiv : the preprint server for health sciences","doi":"10.1101/2024.11.12.24317193","pmid":"39677436","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07796","title":"Semaglutide as an Adjunctive Therapy to Standard Management for Idiopathic Intracranial Hypertension: A Real-World Data-Based Retrospective Analysis.","authors":"Azzam, Ahmed Y; Essibayi, Muhammed Amir; Vaishnav, Dhrumil; Azab, Mohammed A; Morsy, Mahmoud M; Elamin, Osman; Zomia, Ahmed Saad Al; Alotaibi, Hammam A; Alamoud, Ahmed; Mohamed, Adham A; Ahmed, Omar S; Elswedy, Adam; Atallah, Oday; Abukhadijah, Hana J; Dmytriw, Adam A; Altschul, David J","year":2024,"journal":"medRxiv : the preprint server for health sciences","doi":"10.1101/2024.11.12.24317197","pmid":"39677446","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"After propensity score matching (635 patients per group), semaglutide as adjunctive therapy showed significant improvements at 3 months:\n- Visual disturbances: RR 0.28 (72% risk reduction, p=0.0001)\n- Papilledema: RR 0.366 (63% risk reduction, p=0.0001)\n- Headache: RR 0.578 (42% risk reduction, p=0.0001)\n- Refractory disease: RR 0.60 (40% risk reduction, p=0.0001)\n\nBenefits persisted through 24 months of follow-up. BMI showed progressive reduction, with a baseline-adjusted difference of -1.38 kg/m² at 24 months (p<0.0001). All comparisons were highly statistically significant.","whyItMatters":"IIH is a debilitating condition with limited treatment options — current standard care includes acetazolamide, weight management counseling, and sometimes surgical interventions like optic nerve sheath fenestration or cerebrospinal fluid shunting. If semaglutide can dramatically improve outcomes by addressing the obesity driver of IIH, it could represent a paradigm shift in management, potentially reducing the need for invasive procedures and preventing irreversible vision loss.","specificNumbers":"","methodology":"Retrospective cohort analysis using real-world data comparing IIH patients receiving semaglutide plus standard therapy versus standard therapy alone. Propensity score matching was used to create balanced cohorts of 635 patients each. Primary outcomes included papilledema, headache, visual disturbances, and refractory disease status measured at 3, 6, 12, and 24 months. Secondary outcomes included BMI changes.","limitations":"This is a retrospective analysis of real-world data published as a preprint (medRxiv), not yet peer-reviewed. Propensity score matching reduces but does not eliminate confounding compared to randomization. The real-world data source is not specified, and potential biases in treatment selection, outcome ascertainment, and completeness of follow-up cannot be fully controlled. The relatively modest BMI reduction (-1.38 kg/m²) compared to the large clinical improvements raises questions about whether the benefits are mediated by weight loss alone."},{"rthcId":"RPEP-07797","title":"Identification of Wandering Masses and Tumor Heterogeneity on 68Ga-DOTATATE and 18F-FDG PET/CT in Metastatic Grade II Neuroendocrine Tumor with Increased Somatostatin Receptor Expression After Combined Chemotherapy and PRRT.","authors":"Baberwal, Parth; Parghane, Rahul; Basu, Sandip","year":2024,"journal":"Journal of nuclear medicine technology, 52(3), 272-273","doi":"10.2967/jnmt.123.267286","pmid":"39237338","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07798","title":"Retrospective review of seven patients with obesity simultaneously treated with a combination of a glucagon-like peptide-1 receptor agonist and a meal replacement product.","authors":"Bacus, Catherine; South, Terri-Lynne; Raudszus, Sonia; Johansen, Odd Erik","year":2024,"journal":"Obesity pillars, 12, 100138","doi":"10.1016/j.obpill.2024.100138","pmid":"39416284","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07799","title":"Transformative weight loss with Dulaglutide: A case report of success in a challenging patient profile of an ex-sumo wrestler.","authors":"Bade, Sohail; Bade, Sahil; Sharma, Grishma; Bhurtel, Narayan; Singh, Yadvinder; Paudel, Sudip; Magar, Frena Pulami; Chapagain, Kshitij","year":2024,"journal":"Clinical case reports, 12(9), e9403","doi":"10.1002/ccr3.9403","pmid":"39219781","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The patient achieved a 40 kg weight loss (21% of body weight) and a BMI reduction from 49.66 to approximately 39.4 kg/m² over 6 months of dulaglutide treatment. This occurred despite multiple factors working against weight loss:\n\n• Multiple antipsychotic medications for bipolar II disorder (known to cause weight gain)\n• Non-compliance with lifestyle modifications\n• Resistance to conventional treatment with metformin\n• History as a professional sumo wrestler (extreme prior weight conditioning)\n\nNo side effects were reported, and glycemic control improved alongside the weight loss.","whyItMatters":"This case demonstrates that GLP-1 agonists can work even in patients where everything seems stacked against success — extreme obesity, psychiatric medications that promote weight gain, and poor adherence to lifestyle changes. It highlights dulaglutide's potential in 'treatment-resistant' obesity cases and supports considering GLP-1 therapy for patients on antipsychotic medications, a population at particularly high risk for metabolic complications.","specificNumbers":"","methodology":"Single patient case report documenting the clinical course of a 27-year-old male former sumo wrestler treated with dulaglutide for morbid obesity with multiple comorbidities. Weight, BMI, and glycemic parameters were tracked over 6 months of treatment.","limitations":"This is a single case report with no control group or blinding. Case reports represent the lowest level of clinical evidence. The dramatic result in one patient cannot be generalized to broader populations. Specific dulaglutide dosing is not detailed in the abstract. The 6-month follow-up is relatively short — long-term weight maintenance is unknown. The interaction between dulaglutide and multiple antipsychotic medications was not systematically characterized."},{"rthcId":"RPEP-07800","title":"A systematic review of GLP-1 on anthropometrics, metabolic and endocrine parameters in patients with PCOS.","authors":"Bader, Salwa; Bhatti, Rahila; Mussa, Bashair; Abusanana, Salah","year":2024,"journal":"Women's health (London, England), 20, 17455057241234530","doi":"10.1177/17455057241234530","pmid":"38444070","tags":["glp-1-agonist","pcos"],"studyType":"systematic-review","evidenceStrength":"strong","keyFinding":"Across 8 studies with 486 PCOS patients (ages 18-45, follow-up 12-32 weeks), GLP-1 receptor agonists consistently reduced BMI, waist circumference, fat mass, and visceral fat mass. Combined GLP-1 and metformin therapy produced greater reductions in these measurements compared to either treatment alone or other comparators.\n\nGLP-1 agonists also improved some endocrine and metabolic parameters of PCOS, though the abstract notes the effects on these parameters \"remain elusive\" and vary across studies. The overall conclusion supports GLP-1 drugs as effective for weight reduction and metabolic improvement in PCOS, with combination therapy showing the most promise.","whyItMatters":"PCOS is the most common endocrine disorder in reproductive-age women, and weight loss is considered first-line treatment because it can improve nearly every aspect of the syndrome — from irregular periods to hormone imbalances to insulin resistance. But losing weight with PCOS is notoriously difficult. GLP-1 drugs offer a pharmacological tool to achieve meaningful weight loss, and this review suggests they may also directly improve the hormonal disturbances that characterize PCOS, making them a potentially powerful option for this underserved patient population.","specificNumbers":"8 studies; 486 patients; ages 18-45; 12-32 week follow-up; reduced BMI, waist circumference, fat mass, visceral fat; combination therapy superior to monotherapy","methodology":"Systematic review of longitudinal cohort studies from Ovid Medline, PubMed Central, and Cochrane Library (2015-2022). Included studies enrolled women diagnosed with PCOS per 2003 Rotterdam or 1990 NIH criteria. Evaluated GLP-1 receptor agonist monotherapy and GLP-1/metformin combination therapy effects on anthropometric, endocrine, and metabolic parameters.","limitations":"Only 8 studies (486 patients); short follow-up (12-32 weeks); various GLP-1 drugs/doses; no meta-analysis; excludes newest agents; long-term safety and reproductive outcomes not assessed."},{"rthcId":"RPEP-07801","title":"Development and validation of stability-indicating assay method and identification of force degradation products of glucagon-like peptide-1 synthetic analog Exenatide using liquid chromatography coupled with Orbitrap mass spectrometer.","authors":"Badgujar, Devendra; Maskar, Tejas; Paritala, Sree Teja; Sharma, Nitish","year":2024,"journal":"European journal of mass spectrometry (Chichester, England), 30(3-4), 171-186","doi":"10.1177/14690667241262935","pmid":"39056322","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07802","title":"Size-exclusion LC-UV/HRMS based method for the analysis of aggregates in synthetic GLP-1 analog liraglutide and evaluation of excipient impact on aggregation.","authors":"Badgujar, Devendra; Bawake, Sanket; Chawathe, Ashwini; Sharma, Nitish","year":2024,"journal":"Biomedical chromatography : BMC, 38(10), e5983","doi":"10.1002/bmc.5983","pmid":"39113387","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A validated size-exclusion chromatography method (SEC-LC-UV/HRMS) was developed to detect and characterize aggregates in the GLP-1 peptide drug liraglutide under various stress conditions. Photolytic, thermal, freeze-thaw, and mechanical shaking stress all induced different levels of aggregation. The study also evaluated how common pharmaceutical excipients and surfactants affect liraglutide aggregation and stability over time, providing guidance for formulation development.","whyItMatters":"Peptide drug aggregation is a critical quality concern — aggregates can reduce drug efficacy and potentially cause immune reactions in patients. As GLP-1 drugs like liraglutide become some of the most prescribed medications globally, ensuring their stability and quality is essential. This analytical method helps manufacturers and biosimilar developers monitor and prevent aggregation during production and storage.","specificNumbers":"SEC-LC-UV/HRMS method · validated for specificity, accuracy, precision, linearity · photolytic, thermal, freeze-thaw, shaking stress conditions tested · excipient impact on aggregation evaluated","methodology":"Size exclusion chromatography coupled with UV detection and high-resolution mass spectrometry was developed and validated to separate and identify liraglutide aggregates. Liraglutide was subjected to various stress conditions (light, heat, freeze-thaw, shaking). Excipients and surfactants commonly used in peptide formulations were tested for their impact on aggregation levels and physicochemical stability.","limitations":"This is a purely analytical/quality control study with no clinical or biological outcomes. The stress conditions used in the lab may not perfectly replicate real-world storage and handling. The study focused on liraglutide; applicability to other GLP-1 RA peptides would need separate validation. Aggregate immunogenicity was not assessed."},{"rthcId":"RPEP-07803","title":"Peptide-Drug Conjugate with Statistically Designed Transcellular Peptide for Psoriasis-Like Inflammation.","authors":"Bae, Do Hyun; Bae, Hayeon; Yu, Hyung-Seok; Dorjsembe, Banzragch; No, Young Hyun; Kim, Taejung; Kim, Nam Hyeong; Kim, Jin-Woo; Kim, Jiyool; Lee, Bok-Soo; Kim, Ye Ji; Park, Seongchan; Khaleel, Zinah Hilal; Sa, Deok Hyang; Lee, Eui-Chul; Lee, Jaecheol; Ham, Jungyeob; Kim, Jin-Chul; Kim, Yong Ho","year":2024,"journal":"Advanced healthcare materials, 13(15), e2303480","doi":"10.1002/adhm.202303480","pmid":"38421096","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07804","title":"CaV3.2 T-type calcium channels contribute to CGRP- induced allodynia in a rodent model of experimental migraine.","authors":"Baggio, Darciane F; Gambeta, Eder; Souza, Ivana A; Huang, Sun; Zamponi, Gerald W; Chichorro, Juliana G","year":2024,"journal":"The journal of headache and pain, 25(1), 219","doi":"10.1186/s10194-024-01921-0","pmid":"39695919","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07805","title":"High-throughput assay for regulated secretion of neuropeptides in mouse and human neurons.","authors":"Baginska, Urszula; Balagura, Ganna; Toonen, Ruud F; Verhage, Matthijs","year":2024,"journal":"The Journal of biological chemistry, 300(6), 107321","doi":"10.1016/j.jbc.2024.107321","pmid":"38677517","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The NPY-Nanoluc chimera accurately colocalized with endogenous dense core vesicle (DCV) markers in neurons, with minimal mislocalization to other cellular compartments. The reporter successfully detected DCV exocytosis in both rodent neurons and human neurons derived from induced pluripotent stem cells.\n\nThe assay showed the same calcium, RAB3, and STXBP1/MUNC18 dependence as established low-throughput methods, confirming its biological accuracy. It correctly reported modulation by known pharmacological agents (diacylglycerol analog and calcium channel blocker) and demonstrated higher sensitivity than the widely used single-cell low-throughput assay.","whyItMatters":"With over 100 neuropeptides in the brain linked to conditions from depression to epilepsy, researchers need faster ways to study how these signals are released. Current methods are slow and can only measure one cell at a time. This high-throughput assay could dramatically accelerate drug screening for neurological disorders by enabling large-scale testing of compounds that modulate neuropeptide secretion.","specificNumbers":"","methodology":"Researchers engineered a chimeric protein by fusing neuropeptide Y (NPY) to Nanoluc luciferase. This reporter was expressed in mouse neurons and human induced pluripotent stem cell-derived neurons. They validated its localization to dense core vesicles using colocalization with endogenous DCV markers, then tested its ability to report exocytosis under various conditions including depolarization, calcium manipulation, and pharmacological modulation. Performance was compared against established single-cell low-throughput assays.","limitations":"The assay measures bulk neuropeptide release from neuronal populations rather than single-cell dynamics. The reporter uses an exogenous NPY-Nanoluc construct, which may not perfectly replicate the behavior of all endogenous neuropeptides. Validation was performed in vitro, so in vivo applicability remains to be demonstrated. The induced pluripotent stem cell-derived human neurons may not capture the full diversity of neuronal subtypes."},{"rthcId":"RPEP-07806","title":"Neurobiological mechanisms of botulinum neurotoxin-induced analgesia for neuropathic pain.","authors":"Bagues, Ana; Hu, Jiaxin; Alshanqiti, Ishraq; Chung, Man-Kyo","year":2024,"journal":"Pharmacology & therapeutics, 259, 108668","doi":"10.1016/j.pharmthera.2024.108668","pmid":"38782121","tags":[],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Botulinum neurotoxins (BoNTs) relieve neuropathic pain through multiple mechanisms that extend far beyond their well-known ability to block neurotransmitter release at the injection site. After peripheral injection, BoNTs are taken up by nerve terminals and reduce the release of pain signaling molecules — glutamate, CGRP, and substance P — decreasing neurogenic inflammation locally.\n\nCritically, BoNTs are also retrogradely transported along nerve fibers to sensory ganglia and central nerve terminals, where they decrease expression of pain-promoting genes and reduce neurotransmitter release from central terminals. This likely reduces central sensitization in the spinal cord. The analgesic effect requires intact TRPV1-expressing pain fibers and substance P/neurokinin-1 receptor signaling.\n\nEngineered BoNTs targeting specific nociceptive pathways are now being developed to improve safety and efficacy for chronic pain treatment.","whyItMatters":"Neuropathic pain — from conditions like diabetic neuropathy, shingles, and trigeminal neuralgia — is notoriously difficult to treat. While botulinum toxin is already approved for migraines, understanding exactly how it reduces pain could unlock more targeted treatments with fewer side effects. This review maps out the full pathway from injection site to spinal cord, revealing why BoNTs work and how engineered versions could work better.","specificNumbers":"BoNT reduces: glutamate, CGRP, substance P release · Acts at: peripheral terminals, sensory ganglia, central terminals · Requires: TRPV1+ afferents, substance P/NK1R signaling","methodology":"This is a narrative review synthesizing published preclinical and clinical research on the mechanisms by which botulinum neurotoxins produce pain relief. The authors examined evidence from animal models, knockout studies, and clinical observations to map the neurobiological pathways involved.","limitations":"As a review article, this synthesizes existing research rather than presenting new data. Many of the mechanistic insights come from animal models and may not fully translate to humans. Whether BoNT's central nervous system effects are direct (via transport across synapses) or indirect (secondary to peripheral changes) remains unresolved and controversial."},{"rthcId":"RPEP-07807","title":"A 14-amino acid cationic peptide Bolespleenin334-347 from the marine fish mudskipper Boleophthalmus pectinirostris exhibiting potent antimicrobial activity and therapeutic potential.","authors":"Bai, Yuqi; Zhang, Weibin; Zheng, Wenbin; Meng, Xin-Zhan; Duan, Yingyi; Zhang, Chang; Chen, Fangyi; Wang, Ke-Jian","year":2024,"journal":"Biochemical pharmacology, 226, 116344","doi":"10.1016/j.bcp.2024.116344","pmid":"38852647","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Bolespleenin334-347 demonstrated broad-spectrum antibacterial activity against both Gram-negative (A. baumannii) and Gram-positive (S. aureus) bacteria. Its mechanism involves dual action: disrupting bacterial membrane integrity causing cellular content leakage and inducing endogenous reactive oxygen species (ROS) accumulation within bacteria.\n\nThe peptide effectively inhibited biofilm formation by both A. baumannii and S. aureus, and critically, long-term treatment did not induce resistance development. Activity was maintained against clinically multidrug-resistant strains. Most impressively, in a mouse model of MRSA-induced superficial skin infection, Bolespleenin334-347 showed superior efficacy to both LL-37 and vancomycin, significantly reducing bacterial load and promoting better wound healing. The peptide also demonstrated good thermal stability and sodium ion tolerance.","whyItMatters":"MRSA kills tens of thousands of people annually, and new antibiotics against it are desperately needed. Most antimicrobial peptides never advance beyond in vitro testing because they don't work well in live animals. This peptide cleared that critical hurdle — outperforming even vancomycin (the standard MRSA treatment) in a skin infection model. Its tiny size (14 amino acids), stability, and resistance to bacterial resistance development make it an unusually promising candidate for topical anti-MRSA therapy.","specificNumbers":"","methodology":"The peptide was identified from a gene in B. pectinirostris upregulated during bacterial challenge. Antibacterial activity was assessed by MIC determination against multiple species including drug-resistant clinical isolates. Mechanism studies used membrane integrity assays, ROS quantification, and electron microscopy. Anti-biofilm activity and resistance development were evaluated through serial passage and biofilm formation assays. In vivo efficacy was tested in a mouse MRSA skin infection model with comparison to LL-37 and vancomycin, measuring bacterial load and wound healing.","limitations":"The mouse skin infection model tests only topical application, so systemic efficacy and safety remain unknown. The full antibacterial spectrum (MIC values against specific strains) was not detailed in the abstract. Pharmacokinetics, serum stability, and potential immunogenicity in mammals were not reported. The specific doses used in the mouse model versus LL-37 and vancomycin comparators were not provided, making it difficult to assess whether the comparison was at equivalent concentrations. Manufacturing costs for a peptide containing five consecutive arginines may be significant."},{"rthcId":"RPEP-07808","title":"Recent advances in peptide-based therapies for obesity and type 2 diabetes.","authors":"Bailey, Clifford J; Flatt, Peter R; Conlon, J Michael","year":2024,"journal":"Peptides, 173, 171149","doi":"10.1016/j.peptides.2024.171149","pmid":"38184193","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide (available as weekly injection or daily pill) and tirzepatide (weekly injection targeting both GLP-1 and GIP receptors) have achieved HbA1c reductions of over 2% and body weight reductions of over 10% in type 2 diabetes patients. In non-diabetic obese individuals treated at higher doses, weight loss exceeded 15%.\n\nEmerging evidence shows cardio-protective and potentially reno-protective effects. Next-generation therapies in early clinical development — retatrutide (triple GLP-1/GIP/glucagon agonist) and CagriSema (semaglutide + amylin analogue cagrilintide) — have demonstrated even stronger efficacy. Gastrointestinal side effects are generally mild-to-moderate and transient, though they cause some patients to discontinue treatment.","whyItMatters":"Incretin-based peptide therapies represent the most significant advance in diabetes and obesity treatment in decades. The ability to achieve double-digit weight loss percentages and substantial blood sugar control with a single weekly injection is reshaping clinical practice. The emergence of dual and triple agonists suggests we're only at the beginning of what peptide-based therapies can achieve for metabolic diseases.","specificNumbers":"","methodology":"This is a narrative review of recent large clinical trials involving incretin-based peptide therapies for type 2 diabetes and obesity, synthesizing efficacy, safety, and emerging data on cardiovascular and renal outcomes across multiple drug classes.","limitations":"As a narrative review, this article synthesizes existing trial data rather than presenting new primary research. Most large trials have been relatively short-term (1-2 years), and the long-term safety and durability of weight loss after treatment cessation remain uncertain. Cost and access barriers limit the real-world impact of these therapies. The review primarily covers completed trials and may not capture the most recent pipeline developments."},{"rthcId":"RPEP-07809","title":"Liraglutide Protects Cardiomyocytes against Isoprenaline-Induced Apoptosis in Experimental Takotsubo Syndrome.","authors":"Bajic, Zorislava; Sobot, Tanja; Amidzic, Ljiljana; Vojinovic, Natasa; Jovicic, Sanja; Gajic Bojic, Milica; Djuric, Dragan M; Stojiljkovic, Milos P; Bolevich, Sergey; Skrbic, Ranko","year":2024,"journal":"Biomedicines, 12(6)","doi":"10.3390/biomedicines12061207","pmid":"38927414","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07810","title":"Glucagon-like peptide agonists for weight management in antipsychotic-induced weight gain: A systematic review and meta-analysis.","authors":"Bak, Maarten; Campforts, Bea; Domen, Patrick; van Amelsvoort, Therese; Drukker, Marjan","year":2024,"journal":"Acta psychiatrica Scandinavica, 150(6), 516-529","doi":"10.1111/acps.13734","pmid":"39048532","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07811","title":"Impact of semaglutide on weight and functional outcomes among obese heart failure patients: a propensity scores matching analysis.","authors":"Balata, Mahmoud; Becher, Marc Ulrich","year":2024,"journal":"BMC cardiovascular disorders, 24(1), 590","doi":"10.1186/s12872-024-04275-2","pmid":"39462311","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07812","title":"A Cancer Nanovaccine for Co-Delivery of Peptide Neoantigens and Optimized Combinations of STING and TLR4 Agonists.","authors":"Baljon, Jessalyn J; Kwiatkowski, Alexander J; Pagendarm, Hayden M; Stone, Payton T; Kumar, Amrendra; Bharti, Vijaya; Schulman, Jacob A; Becker, Kyle W; Roth, Eric W; Christov, Plamen P; Joyce, Sebastian; Wilson, John T","year":2024,"journal":"ACS nano, 18(9), 6845-6862","doi":"10.1021/acsnano.3c04471","pmid":"38386282","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07813","title":"Effectiveness and Tolerability of Anti-Calcitonin Gene-Related Peptide Therapy for Migraine and Other Chronic Headaches in Adolescents and Young Adults: A Retrospective Study in the USA.","authors":"Bandatmakur, Anjaneya Shankar Madhav; Dave, Pooja; Kerr, Melissa; Brunick, Colin; Wen, Sijin; Hansen, Nicholas","year":2024,"journal":"Brain sciences, 14(9)","doi":"10.3390/brainsci14090879","pmid":"39335375","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 23 adolescents and young adults (ages 12-21) with treatment-resistant migraines:\n\n- 91.3% experienced reduced migraine duration and intensity\n- 82.6% reported improvements in other bothersome symptoms\n- 73.9% had improved response to rescue medications\n- 78.3% reduced rescue medication use by more than 50%\n- 56.5% had fewer emergency room visits\n- 82.6% had significant headache day reductions at 1 month, 87% at 3 months\n- Nearly 40% had >50% reduction in headache days at both timepoints\n- 95.7% reported no side effects\n- 69.6% chose to continue treatment\n\nGreatest benefits were in patients treated for >6 months. Most patients (78.3%) had chronic migraine.","whyItMatters":"Young people with chronic migraine face a double burden: the condition severely impacts their development, schooling, and mental health, while treatment options are limited — many medications are used off-label with significant side effects, and insurance denial rates are high. Showing that anti-CGRP therapies are both effective and well-tolerated in this age group provides crucial evidence for expanding access to these peptide-targeting treatments for young patients.","specificNumbers":"","methodology":"Retrospective study at a specialized pediatric headache center over 3 years. 23 patients ages 12-21 with migraine or chronic daily headaches unresponsive to standard treatments received anti-CGRP therapies: monoclonal antibodies (erenumab, fremanezumab, galcanezumab) and/or small-molecule CGRP receptor antagonists (ubrogepant, rimegepant, atogepant), sometimes combined with OnabotulinumtoxinA. Data were extracted from electronic medical records with structured visit templates. Patient satisfaction was assessed through telephone follow-ups and message reviews.","limitations":"The sample size is very small (23 patients), severely limiting statistical power and generalizability. The retrospective design introduces potential selection and recall bias. There was no control group for comparison. The study was conducted at a single specialized center. Multiple different anti-CGRP agents were used, making it difficult to assess individual drug effects. Insurance coverage barriers may have introduced selection bias toward certain patient characteristics. Long-term safety data beyond the study period are not available."},{"rthcId":"RPEP-07814","title":"Virus-like particle-mediated delivery of structure-selected neoantigens demonstrates immunogenicity and antitumoral activity in mice.","authors":"Barajas, Ana; Amengual-Rigo, Pep; Pons-Grífols, Anna; Ortiz, Raquel; Gracia Carmona, Oriol; Urrea, Victor; de la Iglesia, Nuria; Blanco-Heredia, Juan; Anjos-Souza, Carla; Varela, Ismael; Trinité, Benjamin; Tarrés-Freixas, Ferran; Rovirosa, Carla; Lepore, Rosalba; Vázquez, Miguel; de Mattos-Arruda, Leticia; Valencia, Alfonso; Clotet, Bonaventura; Aguilar-Gurrieri, Carmen; Guallar, Victor; Carrillo, Jorge; Blanco, Julià","year":2024,"journal":"Journal of translational medicine, 22(1), 14","doi":"10.1186/s12967-023-04843-8","pmid":"38172991","tags":[],"studyType":"animal study","evidenceStrength":"low","keyFinding":"Researchers developed a two-part innovation for cancer vaccines: a new computational algorithm (NOAH) that selects neoantigen peptides based on how they interact with both MHC molecules and T cell receptors (not just MHC binding alone), and an engineered virus-like particle (VLP) platform based on HIV-1 Gag that displays high copy numbers of these selected neoantigens. In a mouse melanoma model, VLPs loaded with neoantigens selected for enhanced TCR interaction generated new anti-tumor immune responses and delayed tumor growth. The study demonstrates that incorporating TCR interaction into neoantigen selection improves the immunogenicity of peptide cancer vaccines.","whyItMatters":"Current neoantigen prediction tools have poor accuracy because they mostly predict whether a peptide will bind MHC molecules — a necessary but insufficient condition for triggering an immune response. By also predicting how the peptide-MHC complex interacts with T cell receptors, the NOAH algorithm addresses a key bottleneck in personalized cancer vaccine development. Combined with an efficient VLP delivery platform that mimics viral structure to stimulate strong immune responses, this represents an improved pipeline from neoantigen identification to vaccine delivery.","specificNumbers":"NOAH algorithm incorporating MHC-I binding + TCR interaction · HIV-1 Gag-based VLPs · High copy neoantigen display · B16-F10 melanoma model · Delayed tumor growth","methodology":"The researchers developed the Neoantigen Optimization Algorithm (NOAH) incorporating structural prediction of peptide/MHC-I and peptide/MHC-I/TCR interactions. Neoantigens selected by NOAH were displayed on engineered HIV-1 Gag-based virus-like particles (neoVLPs) at high copy numbers. These neoVLPs were tested in B16-F10 melanoma mice for immunogenicity (generating new tumor-specific immune responses) and therapeutic efficacy (tumor growth delay in challenge experiments).","limitations":"This is a preclinical mouse study using the B16-F10 melanoma model — one of the most commonly used but also most challenging mouse tumor models. The NOAH algorithm's accuracy improvement over existing methods is not quantified in the abstract. Human tumors have far more complex mutational landscapes and immune microenvironments. The HIV-1 Gag-based VLP platform, while effective in mice, may face manufacturing, regulatory, and perception challenges in clinical development. The study shows tumor growth delay but not complete rejection."},{"rthcId":"RPEP-07815","title":"Satiety: a gut-brain-relationship.","authors":"Barakat, Ghinwa M; Ramadan, Wiam; Assi, Ghaith; Khoury, Noura B El","year":2024,"journal":"The journal of physiological sciences : JPS, 74(1), 11","doi":"10.1186/s12576-024-00904-9","pmid":"38368346","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07816","title":"Safety and Efficacy of Switching Patients With Type 2 Diabetes From Glucagon-Like Peptide-1 Receptor Agonists to Tirzepatide: A Case Series.","authors":"Barakat, Sami; Ramdeen, Shannon; Khaimova, Rebecca","year":2024,"journal":"Hospital pharmacy, 59(6), 614-619","doi":"10.1177/00185787241266803","pmid":"39449861","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07817","title":"The preclinical discovery and development of atogepant for migraine prophylaxis.","authors":"Baraldi, Carlo; Beier, Dagmar; Martelletti, Paolo; Pellesi, Lanfranco","year":2024,"journal":"Expert opinion on drug discovery, 19(7), 783-788","doi":"10.1080/17460441.2024.2365379","pmid":"38856039","tags":[],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Atogepant is a second-generation CGRP receptor antagonist (gepant) that represents a significant advance in migraine prevention. It works by competitively blocking CGRP receptors, inhibiting trigeminovascular nociception — the pathway directly implicated in migraine pain.\n\nA key advantage over first-generation gepants is its improved safety profile, specifically a reduced risk of liver injury, which was a major limitation of earlier drugs in the class. Atogepant has been approved for the prevention of both episodic and chronic migraine in adults, supported by phase I, II, and III clinical trial data.","whyItMatters":"Migraine is one of the most common neurological disorders globally and disproportionately affects females. The development of atogepant addresses a long-standing need for preventive treatments that target the underlying biology of migraine rather than just managing symptoms. Its improved hepatic safety profile over first-generation gepants removes a major barrier that limited earlier CGRP antagonists, potentially making this class of drugs accessible to more patients.","specificNumbers":"","methodology":"This study is a narrative literature review. The authors conducted a comprehensive search of English peer-reviewed articles from PubMed, ClinicalTrials.gov, and other electronic databases. They reviewed key milestones from preclinical studies through phase I, II, and III clinical trials, as well as regulatory approval history, clinical efficacy data, safety profiles, and drug-drug interaction studies.","limitations":"As a narrative review, this paper synthesizes existing literature rather than presenting new primary data. The authors highlight that drug-drug interaction studies for atogepant have used insufficiently diverse populations. Since migraine disproportionately affects females, the clinical trial populations may not be fully representative of real-world patients, limiting the generalizability of findings."},{"rthcId":"RPEP-07818","title":"Semaglutide and heart failure: Updated meta-analysis.","authors":"Barbagelata, Leandro; Masson, Walter; Lobo, Martín; Bluro, Ignacio","year":2024,"journal":"Current problems in cardiology, 49(9), 102721","doi":"10.1016/j.cpcardiol.2024.102721","pmid":"38908729","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 6 RCTs (28,762 patients) and 2 observational studies:\n\n- Semaglutide group: 14,608 subjects\n- Control/placebo group: 14,716 subjects\n- Heart failure risk: OR 0.74 (95% CI: 0.58-0.94) — a 26% reduction\n- Heterogeneity: I² = 45% (moderate)\n- No evidence of publication bias\n- Sensitivity analysis confirmed robust results","whyItMatters":"Heart failure affects 64 million people worldwide and has a 5-year mortality rate of approximately 50%. Current treatments can slow progression but rarely reverse the condition. A 26% reduction in heart failure events from a drug already widely prescribed for diabetes and obesity could have enormous public health impact. If confirmed in dedicated heart failure trials, semaglutide could become a new standard of care — particularly valuable because it simultaneously addresses weight, diabetes, and cardiovascular risk.","specificNumbers":"","methodology":"This PRISMA-compliant meta-analysis searched for randomized clinical trials and observational cohort studies assessing semaglutide's effects on heart failure-related outcomes with ≥6 months follow-up. Six RCTs and two observational studies met inclusion criteria. Data were pooled using a random-effects model (appropriate given the heterogeneous study designs and populations). Publication bias was assessed analytically, and sensitivity analyses tested the robustness of the overall finding.","limitations":"The meta-analysis includes studies with different patient populations (diabetes trials, obesity trials), different semaglutide doses, and different heart failure definitions, contributing to moderate heterogeneity (I²=45%). Most included trials were not primarily designed to study heart failure outcomes, meaning heart failure events were secondary or exploratory endpoints with potentially inconsistent ascertainment. The inclusion of observational studies alongside RCTs introduces potential confounding. Heart failure subtypes (HFpEF vs. HFrEF) were not distinguished. Individual patient-level data were not available."},{"rthcId":"RPEP-07819","title":"Evaluating the Effectiveness, Tolerability, and Safety of Eptinezumab in High-Frequency and Chronic Migraine in Real World: EMBRACE-The First Italian Multicenter, Prospective, Real-Life Study.","authors":"Barbanti, Piero; Orlando, Bianca; Egeo, Gabriella; d'Onofrio, Florindo; Doretti, Alberto; Messina, Stefano; Autunno, Massimo; Messina, Roberta; Filippi, Massimo; Fiorentini, Giulia; Rotondi, Cristina; Bonassi, Stefano; Aurilia, Cinzia","year":2024,"journal":"Brain sciences, 14(7)","doi":"10.3390/brainsci14070672","pmid":"39061413","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07820","title":"Real world effectiveness of oral semaglutide: Focus on patients with type 2 diabetes older than 75 years.","authors":"Baronti, Walter; Lencioni, Cristina; Occhipinti, Margherita; Nicolucci, Antonio; Cianni, Graziano Di","year":2024,"journal":"Diabetes research and clinical practice, 218, 111928","doi":"10.1016/j.diabres.2024.111928","pmid":"39536977","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07821","title":"The real-world observational prospective study of health outcomes with dulaglutide and liraglutide in type 2 diabetes patients (TROPHIES): resource use and costs of treatment in clinical practice in France, Germany, and Italy.","authors":"Barrett, Annabel; Boye, Kristina S; García-Pérez, Luis-Emilio; Giorgino, Francesco; Guerci, Bruno; Füchtenbusch, Martin; Yu, Maria; Sapin, Hélène; Dib, Anne; Heitmann, Elke; Federici, Marco Orsini; Lebrec, Jérémie","year":2024,"journal":"Journal of medical economics, 27(1), 866-879","doi":"10.1080/13696998.2024.2367919","pmid":"38963346","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07822","title":"Use of glucagon-like peptide-1 receptor agonists in eating disorder populations.","authors":"Bartel, Sara; McElroy, Susan L; Levangie, Danielle; Keshen, Aaron","year":2024,"journal":"The International journal of eating disorders, 57(2), 286-293","doi":"10.1002/eat.24109","pmid":"38135891","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07823","title":"The impact of approved anti-obesity medications on osteoarthritis.","authors":"Baser, Onur; Rodchenko, Katarzyna; Vivier, Elizabeth; Baser, Isabel; Lu, Yuanqing; Mohamed, Munira","year":2024,"journal":"Expert opinion on pharmacotherapy, 25(11), 1565-1573","doi":"10.1080/14656566.2024.2391524","pmid":"39129529","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07824","title":"Semaglutide and obesity: beyond the nutritional and lifestyle intervention?","authors":"Basile, Livia; Cannarella, Rossella; Iuliano, Stefano; Calogero, Aldo E; Condorelli, Rosita A; Greco, Emanuela A; Aversa, Antonio; LA Vignera, Sandro","year":2024,"journal":"Minerva endocrinology, 49(2), 182-195","doi":"10.23736/S2724-6507.23.04103-9","pmid":"39028209","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07825","title":"Neuropeptide Y Y2 receptors in acute and chronic pain and itch.","authors":"Basu, Paramita; Taylor, Bradley K","year":2024,"journal":"Neuropeptides, 108, 102478","doi":"10.1016/j.npep.2024.102478","pmid":"39461244","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review resolves conflicting findings about the NPY Y2 receptor by proposing a G protein switch model. In the normal state, blocking Y2 receptors (with BIIE0246) causes pain and hypersensitivity. After nerve injury or inflammation, the same Y2 blocker paradoxically reduces mechanical and thermal hypersensitivity and improves the emotional dimension of pain. In chronic pain models of latent sensitization, Y2 blockade causes a profound return of pain-like behaviors. This suggests Y2 signaling switches from antinociception (normal) to anti-hyperalgesia (injured) and back to antinociception (remission).","whyItMatters":"The opioid crisis has created urgent demand for non-opioid pain therapies. NPY Y2 receptors represent a largely untapped target in the spinal pain pathway. By clarifying when Y2 antagonists help versus hurt, this review provides a roadmap for developing targeted Y2-based therapies for chronic pain patients — specifically those who do not develop latent sensitization.","specificNumbers":"","methodology":"This is a narrative review synthesizing evidence from neurophysiological slice recordings, behavioral pharmacology studies in animal models, and chronic pain models of latent sensitization. The authors integrated findings across multiple experimental paradigms to propose a unified mechanistic model.","limitations":"This is a review paper synthesizing primarily animal studies — the proposed G protein switch model has not been directly confirmed in humans. The behavioral pharmacology data relies heavily on a single Y2 antagonist (BIIE0246), and off-target effects cannot be entirely ruled out. The concept of latent sensitization and its relevance to human chronic pain conditions is still being established. Clinical translation remains speculative."},{"rthcId":"RPEP-07826","title":"Neuropeptide Y Y2 Receptors in Sensory Neurons Tonically Suppress Nociception and Itch but Facilitate Postsurgical and Neuropathic Pain Hypersensitivity.","authors":"Basu, Paramita; Maddula, Akshitha; Nelson, Tyler S; Prasoon, Pranav; Winter, Michelle K; Herzog, Herbert; McCarson, Kenneth E; Taylor, Bradley K","year":2024,"journal":"Anesthesiology, 141(5), 946-968","doi":"10.1097/ALN.0000000000005184","pmid":"39121458","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07827","title":"Extended peptide receptor radionuclide therapy: evaluating nephrotoxicity and therapeutic effectiveness in neuroendocrine tumor patients receiving more than four treatment cycles.","authors":"Baum, Richard P; Fan, Xin; Jakobsson, Vivianne; Schuchardt, Christiane; Chen, Xiaoyuan; Yu, Fei; Zhang, Jingjing","year":2024,"journal":"European journal of nuclear medicine and molecular imaging, 51(4), 1136-1146","doi":"10.1007/s00259-023-06544-2","pmid":"38040931","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 637 neuroendocrine tumor patients, extending peptide receptor radionuclide therapy (PRRT) beyond the standard 4 cycles was safe and improved survival. The extended treatment group (>4 cycles, n=356) had significantly longer median overall survival (72.8 months) compared to the standard group (4 cycles, n=281, 52.8 months). Cox regression confirmed a 42% lower risk of death (HR 0.580, p<0.001) and 40% lower disease-specific mortality (HR 0.599, p<0.001) in the extended group. Kidney safety was comparable: mean post-treatment creatinine levels did not differ significantly (93.20 vs 89.30 μmol/L, p=0.364), and adverse renal events occurred in only 1.1% of extended vs 0.4% of standard patients.","whyItMatters":"PRRT uses radioactive peptides that bind to somatostatin receptors on neuroendocrine tumors to deliver targeted radiation. The standard protocol limits treatment to 4 cycles due to kidney safety concerns, but this large study shows that additional cycles are safe and provide a meaningful 20-month survival advantage — potentially changing treatment guidelines for patients whose tumors recur or progress.","specificNumbers":"n=637 (281 standard, 356 extended) · median OS 72.8 vs 52.8 months · HR 0.580 (p<0.001) · DSS HR 0.599 (p<0.001) · creatinine 93.20 vs 89.30 μmol/L (p=0.364) · renal events 1.1% vs 0.4% · median follow-up 88.3 months","methodology":"Retrospective analysis of 637 neuroendocrine tumor patients who received at least 4 PRRT cycles. Patients were divided into standard (4 cycles, n=281) and extended (>4 cycles, n=356) groups. Kidney function was assessed via creatinine levels and CTCAE grading. Survival was analyzed using Kaplan-Meier curves and Cox regression. Median follow-up was 88.3 months.","limitations":"Retrospective study design with potential selection bias — patients receiving extended treatment may have been those with better performance status or more favorable disease biology. The study did not randomize patients to standard vs extended treatment. Specific PRRT agents and cumulative doses were not detailed in the abstract."},{"rthcId":"RPEP-07828","title":"Peptide receptor radionuclide therapy (PRRT) in metastatic neuroendocrine tumors of unknown primary (CUP-NETs).","authors":"Baum, Richard P; Wang, Peipei; Jakobsson, Vivianne; Zhao, Tianzhi; Schuchardt, Christiane; Khong, Pek-Lan; Zhang, Jingjing","year":2024,"journal":"Theranostics, 14(1), 133-142","doi":"10.7150/thno.88619","pmid":"38164147","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07829","title":"Hive Products: Composition, Pharmacological Properties, and Therapeutic Applications.","authors":"Bava, Roberto; Castagna, Fabio; Lupia, Carmine; Poerio, Giusi; Liguori, Giovanna; Lombardi, Renato; Naturale, Maria Diana; Bulotta, Rosa Maria; Biondi, Vito; Passantino, Annamaria; Britti, Domenico; Statti, Giancarlo; Palma, Ernesto","year":2024,"journal":"Pharmaceuticals (Basel, Switzerland), 17(5)","doi":"10.3390/ph17050646","pmid":"38794216","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07830","title":"Tirzepatide-Associated Colonic Ischemia.","authors":"Bayless, David; Singh, Jasraj; Park, Byoung Uk; Sweetser, Seth","year":2024,"journal":"ACG case reports journal, 11(11), e01551","doi":"10.14309/crj.0000000000001551","pmid":"39507503","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07831","title":"Energy balance and obesity: the emerging role of glucagon like peptide-1 receptor agonists.","authors":"Beauregard, Noémie; McInnis, Kurt; Goldfield, Gary S; Doucet, Éric","year":2024,"journal":"Current opinion in clinical nutrition and metabolic care, 27(6), 472-478","doi":"10.1097/MCO.0000000000001064","pmid":"39150432","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07832","title":"Estimating Cardiovascular Benefits of Tirzepatide in Sleep Apnea and Obesity: Insight from the SURMOUNT-OSA Trials.","authors":"Beccuti, Guglielmo; Bioletto, Fabio; Parasiliti-Caprino, Mirko; Benso, Andrea; Ghigo, Ezio; Cicolin, Alessandro; Broglio, Fabio","year":2024,"journal":"Current obesity reports, 13(4), 739-742","doi":"10.1007/s13679-024-00592-x","pmid":"39378016","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07833","title":"Two-year efficacy and safety of relugolix combination therapy in women with endometriosis-associated pain: SPIRIT open-label extension study.","authors":"Becker, Christian M; Johnson, Neil P; As-Sanie, Sawsan; Arjona Ferreira, Juan C; Abrao, Mauricio S; Wilk, Krzysztof; Imm, So Jung; Mathur, Vandana; Perry, Julie S; Wagman, Rachel B; Giudice, Linda C","year":2024,"journal":"Human reproduction (Oxford, England), 39(3), 526-537","doi":"10.1093/humrep/dead263","pmid":"38243752","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07834","title":"CGRP Modulating Therapies: An Update.","authors":"Bedrin, Kate; Shah, Tulsi; Vaidya, Shivani; Ailani, Jessica","year":2024,"journal":"Current neurology and neuroscience reports, 24(9), 453-459","doi":"10.1007/s11910-024-01363-w","pmid":"39017828","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07835","title":"A facile strategy for tuning the density of surface-grafted biomolecules for melt extrusion-based additive manufacturing applications.","authors":"Beeren, I A O; Dos Santos, G; Dijkstra, P J; Mota, C; Bauer, J; Ferreira, H; Reis, Rui L; Neves, N; Camarero-Espinosa, S; Baker, M B; Moroni, L","year":2024,"journal":"Bio-design and manufacturing, 7(3), 277-291","doi":"10.1007/s42242-024-00286-2","pmid":"38818303","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07836","title":"Semaglutide-associated kidney injury.","authors":"Begum, Farhana; Chang, Kelly; Kapoor, Krishna; Vij, Rajiv; Phadke, Gautam; Hiser, Wesley M; Wanchoo, Rimda; Sharma, Purva; Sutaria, Nirja; Jhaveri, Kenar D","year":2024,"journal":"Clinical kidney journal, 17(9), sfae250","doi":"10.1093/ckj/sfae250","pmid":"39258261","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07837","title":"Covalent conjugation and non-covalent complexation strategies for intracellular delivery of proteins using cell-penetrating peptides.","authors":"Behzadipour, Yasaman; Hemmati, Shiva","year":2024,"journal":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 176, 116910","doi":"10.1016/j.biopha.2024.116910","pmid":"38852512","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07838","title":"The potential for improved outcomes in the prevention and therapy of diabetic kidney disease through 'stacking' of drugs from different classes.","authors":"Bell, David S H; Jerkins, Terri","year":2024,"journal":"Diabetes, obesity & metabolism, 26(6), 2046-2053","doi":"10.1111/dom.15559","pmid":"38516874","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07839","title":"Tuning Peptide-Based Nanofibers for Achieving Selective Doxorubicin Delivery in Triple-Negative Breast Cancer.","authors":"Bellavita, Rosa; Piccolo, Marialuisa; Leone, Linda; Ferraro, Maria Grazia; Dardano, Principia; De Stefano, Luca; Nastri, Flavia; Irace, Carlo; Falanga, Annarita; Galdiero, Stefania","year":2024,"journal":"International journal of nanomedicine, 19, 6057-6084","doi":"10.2147/IJN.S453958","pmid":"38911501","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The peptide nanofiber (NF-Dox) achieved complete internalization into TNBC cells (MDA-MB 231) within 1 hour, primarily through a translocation mechanism mediated by gH625. The antiproliferative effect of NF-Dox carrying 7.5 µM doxorubicin was equivalent to 50 µM free doxorubicin — a ~6.7-fold dose reduction. The empty carrier (NF) showed no toxicity to either healthy keratinocytes (HaCaT) or TNBC cells. The nanofiber was 250 nm long, 10 nm in diameter, and stable across varying dilution, ionic strength, and pH conditions.\n\nThe on-demand drug release was achieved through an MMP-9-cleavable linker, ensuring doxorubicin was only released in the tumor microenvironment where MMP-9 is overexpressed.","whyItMatters":"Triple-negative breast cancer has the worst prognosis of all breast cancer subtypes and few targeted therapies. Doxorubicin is effective but causes severe side effects (especially heart damage) due to its non-selective distribution. This peptide nanofiber platform achieves the same cancer-killing effect at dramatically lower doses, potentially reducing the devastating side effects that limit doxorubicin use.","specificNumbers":"","methodology":"Amphiphilic peptides were designed to self-assemble into nanofibers decorated with three functional moieties: the cell-penetrating peptide gH625, the EGFR-targeting peptide P22, and doxorubicin linked via an MMP-9-cleavable sequence. Physicochemical characterization included size, stability, and morphology analysis. Biological testing included cellular uptake (internalization kinetics and mechanism), cytotoxicity against TNBC (MDA-MB 231) and healthy cells (HaCaT), and antiproliferative assays comparing NF-Dox to free doxorubicin.","limitations":"All experiments were in vitro using cell lines; no animal tumor models were tested. The study used a single TNBC cell line (MDA-MB 231), and results may differ with other TNBC subtypes. In vivo biodistribution, pharmacokinetics, immune response, and tumor accumulation were not assessed. Manufacturing scalability and reproducibility of the self-assembly process at larger scales are unknown."},{"rthcId":"RPEP-07840","title":"Stabilizing Scaffold for Short Peptides Based on Knottins.","authors":"Beloborodov, Evgenii; Iurova, Elena; Sugak, Dmitrii; Rastorgueva, Eugenia; Pogodina, Evgeniya; Fomin, Aleksandr; Viktorov, Denis; Slesarev, Sergei; Saenko, Yury","year":2024,"journal":"Current cancer drug targets, 24(12), 1275-1285","doi":"10.2174/0115680096285288240118090050","pmid":"38357956","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Short bombesin peptide was incorporated into various domains of arachnid and plant toxin scaffolds containing inhibitory cystine knots via solid-phase peptide synthesis. Placing bombesin between the first and second cysteine residues in arachnid toxins yielded the best results — increased in vitro stability and bioavailability as assessed by HPLC, maintained receptor binding in cell cultures expressing bombesin receptors, and low cytotoxicity confirmed by fluorescence microscopy.","whyItMatters":"Many promising therapeutic peptides fail because they degrade too quickly in the body. This study demonstrates a generalizable approach — using naturally stable toxin scaffolds as carriers — that could be applied beyond bombesin to stabilize other therapeutic peptides, potentially improving peptide-based cancer diagnostics and treatments.","specificNumbers":"","methodology":"Researchers synthesized hybrid peptides by inserting short bombesin sequences into different positions within arthropod and plant toxin scaffold structures using solid-phase peptide synthesis. Stability was tested under various conditions using HPLC, receptor binding was assessed in cancer cell cultures, and toxicity was evaluated using fluorescence microscopy.","limitations":"This was entirely an in vitro study — no animal or human testing was performed. The stability improvements were measured in laboratory conditions, not in living organisms where enzymatic degradation, clearance, and tissue distribution would present additional challenges. Specific quantitative stability improvements were not detailed in the abstract."},{"rthcId":"RPEP-07841","title":"Gut hormone stimulation as a therapeutic approach in oral peptide delivery.","authors":"Beloqui, Ana","year":2024,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 373, 31-37","doi":"10.1016/j.jconrel.2024.07.007","pmid":"38971429","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07842","title":"Migraine treatment consensus document of the Spanish Society of Neurology (SEN), Spanish Society of Family and Community Medicine (SEMFYC), Society of Primary Care Medicine (SEMERGEN) and Spanish Association of Migraine and Headache (AEMICE) on migraine treatment.","authors":"Belvís, Robert; Irimia, Pablo; González, Nuria; García-Ull, Jésica; Pozo-Rosich, Patricia; López-Bravo, Alba; Morollón, Noemí; Quintas, Sonia; Plana, Antoni; Baz, Pablo Gregorio; Tentor, Ana; Gallego Artiles, Natalia; León, Francisco Javier; Pérez Martín, Miguel; Rivera, Inés; Ramírez, Raquel; Colomina, Isabel; Lainez, José Miguel; Pascual, Julio","year":2024,"journal":"Medicina clinica, 163(4), 208.e1-208.e10","doi":"10.1016/j.medcli.2024.02.006","pmid":"38643025","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07843","title":"Untargeted metabolomics reveals the impact of Liraglutide treatment on metabolome profiling and metabolic pathways in type-2 diabetes mellitus.","authors":"Benabdelkamel, Hicham; Sebaa, Rajaa; AlMalki, Reem H; Masood, Afshan; Alfadda, Assim A; Abdel Rahman, Anas M","year":2024,"journal":"Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society, 32(11), 102172","doi":"10.1016/j.jsps.2024.102172","pmid":"39381269","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Untargeted metabolomics profiling of plasma from 20 T2DM patients pre- and post-liraglutide treatment identified 93 endogenous metabolites that were significantly altered — 49 upregulated and 44 downregulated.\n\nKey affected metabolic pathways included:\n- Pentose and glucuronate interconversion — a pathway important for eliminating toxic substances from the body\n- Alanine, aspartate, and glutamate metabolism — amino acid pathways that may improve immune cell function\n- Metabolites involved in defense against oxidative stress were also induced by liraglutide\n\nThese metabolic alterations may partially explain liraglutide's cardiovascular and anti-inflammatory benefits beyond its primary glucose-lowering effect.","whyItMatters":"GLP-1 drugs like liraglutide reduce cardiovascular events and improve multiple health markers beyond blood sugar — but the mechanisms have been largely unknown. By mapping how liraglutide changes the entire metabolic landscape, this study provides molecular-level explanations for its broad benefits. The detoxification and anti-oxidative effects are particularly interesting, as they could explain the drug's protective effects on blood vessels and organs.","specificNumbers":"","methodology":"Plasma samples were collected from 20 type 2 diabetes patients before and after liraglutide treatment (pre-post design, same patients). Untargeted metabolomics was performed to profile all detectable metabolites without preselecting targets. Statistical analyses identified significantly changed metabolites, and pathway/network analyses mapped these changes to known metabolic pathways.","limitations":"The sample size is small (20 patients) and the study uses a pre-post design without a placebo control group, meaning some metabolic changes could reflect disease progression, dietary changes, or other factors rather than drug effects. The duration of liraglutide treatment is not specified in the abstract. Untargeted metabolomics identifies associations but does not prove causation — the metabolic changes could be consequences of improved glucose control rather than direct drug effects. No clinical outcomes are correlated with the metabolomic changes."},{"rthcId":"RPEP-07844","title":"Glycerol Trinitrate Acts Downstream of Calcitonin Gene-Related Peptide in Trigeminal Nociception-Evidence from Rodent Experiments with Anti-CGRP Antibody Fremanezumab.","authors":"Benedicter, Nicola; Vogler, Birgit; Kuhn, Annette; Schramm, Jana; Mackenzie, Kimberly D; Stratton, Jennifer; Dux, Mária; Messlinger, Karl","year":2024,"journal":"Cells, 13(7)","doi":"10.3390/cells13070572","pmid":"38607011","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GTN treatment (5 mg/kg) tended to increase CGRP concentration in trigeminal ganglia after single administration, but repetitive GTN treatment decreased CGRP levels, suggesting store depletion. No significant difference in CGRP concentration was observed between fremanezumab-treated and control antibody-treated animals, indicating GTN increases CGRP production independently of antibody treatment.\n\nBehaviorally, GTN-treated rats spent less time at a sugar solution source and consumed less, indicating suppressed activity and increased facial sensitivity. Under mechanical barrier conditions, fremanezumab partly compensated for GTN's depressive effects, with treated animals being more active. The findings suggest that if CGRP and NO share the same pathway in sensitizing trigeminal afferents, NO acts downstream of CGRP.","whyItMatters":"Understanding the relationship between CGRP and NO in migraine is critical for improving treatment. If NO acts downstream of CGRP, this explains why anti-CGRP therapies (like fremanezumab) help many but not all migraine patients — some migraine signaling may bypass CGRP entirely through NO. This insight could guide development of combination therapies targeting both pathways.","specificNumbers":"","methodology":"Wistar rats of both sexes received subcutaneous fremanezumab (30 mg/kg) or isotype control antibody, followed 1-several days later by intraperitoneal GTN (5 mg/kg, single or 3 consecutive days). Trigeminal ganglia were harvested for CGRP quantification by ELISA. Behavioral testing used a semi-automated system where rats accessed a sugar solution through mechanical or thermal barriers, measuring approach frequency, residence time, and consumption.","limitations":"The behavioral findings showed trends rather than statistically significant differences in many comparisons, likely due to small group sizes. The GTN model, while established for migraine research, may not fully replicate human migraine mechanisms. Sex differences in CGRP levels add complexity. The pathway inference (NO downstream of CGRP) is based on indirect evidence from antibody and GTN interactions, not direct pathway mapping."},{"rthcId":"RPEP-07845","title":"Peptide Receptor Radionuclide Therapy Using 177Lu-DOTATATE: Nursing Roles in Managing Patients With Gastroenteropancreatic Neuroendocrine Tumors.","authors":"Bennett, Bonita; Gardner, Linda; Ryan, Pamela","year":2024,"journal":"Clinical journal of oncology nursing, 28(1), 79-87","doi":"10.1188/24.CJON.79-87","pmid":"38252861","tags":[],"studyType":"review","evidenceStrength":"low","keyFinding":"This clinical practice review describes the nursing roles in administering peptide receptor radionuclide therapy (PRRT) using 177Lu-DOTATATE for patients with somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs). The peptide-based therapy targets somatostatin receptors expressed on neuroendocrine tumor cells, delivering targeted radiation directly to tumors. Oncology nurses play critical roles in patient assessment, education, direct care during infusion, monitoring for adverse effects, and providing emotional support throughout treatment.","whyItMatters":"PRRT with 177Lu-DOTATATE (Lutathera) represents one of the most successful applications of peptide-based targeted therapy in oncology. As this treatment becomes more widely adopted for neuroendocrine tumors, practical guidance on patient care is essential. This review provides the nursing perspective on managing patients receiving this peptide-targeted radioligand therapy, addressing a gap in clinical education.","specificNumbers":"","methodology":"Clinical practice review based on published literature and the authors' nursing experience. Includes a case study to illustrate key patient care concepts during PRRT administration.","limitations":"This is a narrative practice review, not a research study. It does not present new clinical outcome data, efficacy results, or safety statistics. The guidance is based on the authors' institutional experience, which may not be universally applicable."},{"rthcId":"RPEP-07846","title":"Evaluating appetite/satiety hormones and eating behaviours as predictors of weight loss maintenance with GLP-1RA therapy in adolescents with severe obesity.","authors":"Bensignor, Megan O; Kelly, Aaron S; Kunin-Batson, Alicia; Fox, Claudia K; Freese, Rebecca; Clark, Justin; Rudser, Kyle D; Bomberg, Eric M; Ryder, Justin; Gross, Amy C","year":2024,"journal":"Pediatric obesity, 19(5), e13105","doi":"10.1111/ijpo.13105","pmid":"38339799","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07847","title":"Unraveling neuroprotection with Kv1.3 potassium channel blockade by a scorpion venom peptide.","authors":"Beraldo-Neto, Emidio; Ferreira, Vanessa Florentino; Vigerelli, Hugo; Fernandes, Karolina Rosa; Juliano, Maria Aparecida; Nencioni, Ana Leonor Abrahao; Pimenta, Daniel Carvalho","year":2024,"journal":"Scientific reports, 14(1), 27888","doi":"10.1038/s41598-024-79152-1","pmid":"39537765","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07848","title":"Growth hormone releasing peptide-6 (GHRP-6) prevents doxorubicin-induced myocardial and extra-myocardial damages by activating prosurvival mechanisms.","authors":"Berlanga-Acosta, Jorge; Cibrian, Danay; Valiente-Mustelier, Juan; Suárez-Alba, José; García-Ojalvo, Ariana; Falcón-Cama, Viviana; Jiang, Baohong; Wang, Linlin; Guillén-Nieto, Gerardo","year":2024,"journal":"Frontiers in pharmacology, 15, 1402138","doi":"10.3389/fphar.2024.1402138","pmid":"38873418","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07849","title":"Classical and nonclassical effects of angiotensin-converting enzyme: How increased ACE enhances myeloid immune function.","authors":"Bernstein, Kenneth E; Cao, DuoYao; Shibata, Tomohiro; Saito, Suguru; Bernstein, Ellen A; Nishi, Erika; Yamashita, Michifumi; Tourtellotte, Warren G; Zhao, Tuantuan V; Khan, Zakir","year":2024,"journal":"The Journal of biological chemistry, 300(6), 107388","doi":"10.1016/j.jbc.2024.107388","pmid":"38763333","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"ACE (angiotensin-converting enzyme) has a second, nonclassical function beyond making angiotensin II: when immune cells like macrophages and neutrophils increase their ACE expression, it dramatically boosts their ability to fight tumors, infections, atherosclerosis, and Alzheimer's disease. Genetically modified 'ACE 10/10' mice with increased macrophage ACE were much more resistant to all these conditions. This immune-boosting effect works through an unknown peptide (not angiotensin II) that shifts macrophage metabolism toward increased mitochondrial fat burning and ATP production. Conversely, ACE inhibitor drugs reduce neutrophil bacteria-killing ability in both mice and humans.","whyItMatters":"ACE inhibitors are among the most prescribed drugs worldwide for blood pressure. This review reveals that ACE does far more than regulate blood pressure — it produces an unidentified peptide that supercharges immune cell function. This has profound implications: ACE inhibitors may inadvertently weaken immune responses, and identifying the mystery peptide could create new treatments for cancer, infections, atherosclerosis, and Alzheimer's disease.","specificNumbers":"","methodology":"This is a review article summarizing the authors' extensive research program on nonclassical ACE functions. It draws on data from genetically modified mouse models (ACE 10/10 mice with enhanced macrophage ACE, and NeuACE mice with enhanced neutrophil ACE), metabolic profiling, and studies of ACE inhibitor effects on immune function in mice and humans.","limitations":"Most evidence comes from genetically modified mouse models. The unknown peptide responsible for the immune effects has not been identified or purified. The clinical significance of ACE inhibitor-induced immune suppression in humans needs further study. The review is largely from one research group's body of work."},{"rthcId":"RPEP-07850","title":"Improved glycemic and weight control with Dulaglutide addition in SGLT2 inhibitor treated obese type 2 diabetic patients at high cardiovascular risk in a real-world setting. The AWARE-2 study.","authors":"Berra, Cesare; Manfrini, Roberto; Bifari, Francesco; Cipponeri, Elisa; Ghelardi, Renata; Centofanti, Lucia; Mortola, Umberto; Lunati, Elena; Bucciarelli, Loredana; Cimino, Vincenzo; Folli, Franco","year":2024,"journal":"Pharmacological research, 210, 107517","doi":"10.1016/j.phrs.2024.107517","pmid":"39613122","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07851","title":"Reduced hepatic impairment study to evaluate pharmacokinetics and safety of zavegepant and to inform dosing recommendation for hepatic impairment.","authors":"Bhardwaj, Rajinder; Donohue, Mary K; Madonia, Jennifer; Morris, Beth; Marbury, Thomas C; Matschke, Kyle T; Croop, Robert; Bertz, Richard; Liu, Jing","year":2024,"journal":"Clinical and translational science, 17(7), e13813","doi":"10.1111/cts.13813","pmid":"39014555","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 8 participants with moderate hepatic impairment (Child-Pugh 7-9) versus 8 matched healthy controls, a single 10-mg intranasal zavegepant dose showed approximately 2-fold increase in total AUC0-inf (GLSM ratio 193%, 90% CI: 112-333) and 16% increase in Cmax (GLSM ratio 116%, 90% CI: 69-195). Unbound zavegepant showed similar patterns (~2.3-fold AUC increase, 39% Cmax increase). The unbound fraction was similar between groups (0.13 vs 0.11).\n\nOnly one treatment-emergent adverse event (mild headache) occurred, in a healthy participant. These changes were not considered clinically meaningful, supporting no dose adjustment for mild or moderate hepatic impairment.","whyItMatters":"Migraine patients often have comorbidities including liver disease, and many drugs require dose adjustments for hepatic impairment. This study confirms that zavegepant — the first intranasal CGRP receptor antagonist — can be used at standard doses in patients with liver disease, expanding its clinical utility. For the growing class of CGRP-targeted migraine therapies, knowing which patients need dose modifications is essential for safe prescribing.","specificNumbers":"","methodology":"Phase I pharmacokinetic study comparing a single 10-mg intranasal dose of zavegepant in 8 participants with moderate hepatic impairment (Child-Pugh score 7-9) versus 8 matched participants with normal hepatic function. Both total and unbound plasma zavegepant concentrations were measured. Safety was assessed through adverse event monitoring.","limitations":"The study included only 16 participants (8 per group), which is standard for hepatic impairment PK studies but limits statistical power. Only moderate hepatic impairment was studied — severe impairment data is absent. The study used a single dose, so the effects of repeated dosing in hepatic impairment are unknown. The findings are specific to intranasal delivery and may not apply to other formulations."},{"rthcId":"RPEP-07852","title":"LL-37: Structures, Antimicrobial Activity, and Influence on Amyloid-Related Diseases.","authors":"Bhattacharjya, Surajit; Zhang, Zhizhuo; Ramamoorthy, Ayyalusamy","year":2024,"journal":"Biomolecules, 14(3)","doi":"10.3390/biom14030320","pmid":"38540740","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07853","title":"Mortality and Serious Adverse Events Associated With Glucagon-Like Peptide-1 Receptor Agonists: A Pharmacovigilance Study Using the FDA Adverse Event Reporting System.","authors":"Bhattacharyya, Mehul; Miller, Larry E; Miller, Anna L; Bhattacharyya, Ruemon","year":2024,"journal":"Cureus, 16(8), e65989","doi":"10.7759/cureus.65989","pmid":"39221363","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07854","title":"Common food additive carrageenan inhibits proglucagon expression and GLP-1 secretion by human enteroendocrine L-cells.","authors":"Bhattacharyya, Sumit; Borthakur, Alip; Tobacman, Joanne K","year":2024,"journal":"Nutrition & diabetes, 14(1), 28","doi":"10.1038/s41387-024-00284-4","pmid":"38755184","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The common food additive λ-carrageenan significantly reduced both proglucagon gene expression and GLP-1 peptide secretion in human intestinal L-cells at a concentration of just 1 µg/ml. This inhibition was observed at 10 minutes, 1 hour, and 24 hours of exposure. The effect was confirmed in mouse L-cells as well.\n\nFurthermore, when intestinal epithelial cells were exposed to spent media from carrageenan-treated L-cells, they showed decreased expression of the GLUT-2 glucose transporter, suggesting secondary downstream effects on glucose metabolism beyond direct GLP-1 suppression.","whyItMatters":"With millions of people now taking GLP-1 receptor agonist drugs for diabetes and obesity, discovering that a common processed food additive can suppress the body's own GLP-1 production is significant. Carrageenan is found in many dairy products, plant milks, and processed foods. This study suggests that dietary carrageenan could counteract the effects of GLP-1 medications and impair natural incretin signaling — a finding with direct implications for patients and dietary guidance.","specificNumbers":"1 µg/ml carrageenan concentration · Significant GLP-1 reduction at 10 min, 1 h, and 24 h · GLUT-2 expression reduced at 24 h · Confirmed in both human and mouse L-cells","methodology":"Human intestinal L-cells (NCI-H716) were cultured, deprived overnight of glucose and serum, then exposed to high glucose, 10% fetal bovine serum, and λ-carrageenan (1 µg/ml) for 10 minutes, 1 hour, and 24 hours. Proglucagon mRNA expression and GLP-1 secretion were measured and compared to controls. Results were validated in mouse L-cells (STC-1). Secondary effects were tested by exposing co-cultured human intestinal epithelial cells (LS174T) to conditioned media from treated L-cells.","limitations":"This is entirely an in vitro study using cultured cell lines, which may not accurately replicate the complex gut environment where carrageenan exposure occurs alongside other food components, mucus barriers, and gut microbiota. The carrageenan concentration used (1 µg/ml) may or may not reflect actual intestinal exposure from dietary intake. No human dietary studies were conducted to confirm that eating carrageenan-containing foods actually reduces GLP-1 levels in vivo."},{"rthcId":"RPEP-07855","title":"Management of Acute Pulmonary Embolism: A Review.","authors":"Bhave, Abhay; Dumra, Harjit; Bansal, Sandeep","year":2024,"journal":"The Journal of the Association of Physicians of India, 72(11), 80-91","doi":"10.59556/japi.72.0737","pmid":"39563127","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07856","title":"Alpha-emitter Peptide Receptor Radionuclide Therapy in Neuroendocrine Tumors.","authors":"Bhimaniya, Sudhir; Shah, Hina; Jacene, Heather A","year":2024,"journal":"PET clinics, 19(3), 341-349","doi":"10.1016/j.cpet.2024.03.005","pmid":"38658229","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07857","title":"Efficacy and Safety of Tirzepatide in Patients with Type 2 Diabetes: Analysis of SURPASS-AP-Combo by Different Subgroups.","authors":"Bi, Yan; Lu, Song; Tang, Jiani; Du, Liying; Ji, Linong","year":2024,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 15(5), 1125-1137","doi":"10.1007/s13300-024-01561-2","pmid":"38494574","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07858","title":"A systematic review of the effect of semaglutide on lean mass: insights from clinical trials.","authors":"Bikou, Alexia; Dermiki-Gkana, Foteini; Penteris, Michail; Constantinides, Theodoros K; Kontogiorgis, Christos","year":2024,"journal":"Expert opinion on pharmacotherapy, 25(5), 611-619","doi":"10.1080/14656566.2024.2343092","pmid":"38629387","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07859","title":"Renoprotective effect of liraglutide on diabetic nephropathy by modulation of Krüppel-like transcription factor 5 expression in rats.","authors":"Bin Dayel, Anfal F; Alrasheed, Nouf M; Alonazi, Asma S; Alamin, Maha A; Al-Mutairi, Nawal M; Alateeq, Raghad A","year":2024,"journal":"The Journal of pharmacy and pharmacology, 76(12), 1563-1571","doi":"10.1093/jpp/rgae127","pmid":"39403839","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In streptozotocin/high-fat-diet diabetic rats, 21 days of liraglutide treatment (200 μg/kg/day subcutaneous) produced multiple renoprotective effects: decreased serum biomarkers of diabetic nephropathy, reduced histological abnormalities in kidney tissues, and decreased protein expression of three key molecules in the lysophosphatidic acid (LPA) axis — PCNA (a cell proliferation marker), autotaxin (the enzyme that produces LPA), and KLF5 (the transcription factor that regulates autotaxin expression).\n\nThe downregulation of all three components suggests liraglutide works upstream through KLF5 to suppress the entire LPA signaling cascade that drives kidney fibrosis and damage in diabetes.","whyItMatters":"Diabetic nephropathy is the leading cause of kidney failure worldwide, affecting about 40% of diabetic patients. While GLP-1 drugs are known to have kidney-protective effects in clinical trials, the molecular mechanisms have been unclear. This study identifies a specific pathway — the KLF5-autotaxin-LPA axis — that liraglutide modulates, which could lead to more targeted therapies for diabetic kidney disease and help identify which patients are most likely to benefit from GLP-1 treatment.","specificNumbers":"","methodology":"Wistar albino rats were divided into four groups: nondiabetic control, liraglutide-treated nondiabetic, diabetic control, and liraglutide-treated diabetic. Diabetes was induced with intraperitoneal streptozotocin (30 mg/kg) combined with a high-fat diet. Control groups received normal saline for 42 days. Treatment groups received saline for 21 days followed by liraglutide (200 μg/kg/day subcutaneous) for 21 days. Outcomes included serum diabetic nephropathy biomarkers, kidney histology, and protein expression analysis of PCNA, autotaxin, and KLF5.","limitations":"This is an animal study using a chemically-induced diabetes model (streptozotocin), which doesn't perfectly replicate human type 2 diabetes. The treatment duration of only 21 days is short for a chronic condition like diabetic nephropathy. The study doesn't clarify whether liraglutide's kidney effects are independent of its blood sugar lowering — some of the observed benefits could be secondary to improved glycemic control. Specific quantitative data for the biomarker and protein expression changes are not reported in the abstract."},{"rthcId":"RPEP-07860","title":"Impact of Collagen Peptide Supplementation in Combination with Long-Term Physical Training on Strength, Musculotendinous Remodeling, Functional Recovery, and Body Composition in Healthy Adults: A Systematic Review with Meta-analysis.","authors":"Bischof, Kevin; Moitzi, Anna Maria; Stafilidis, Savvas; König, Daniel","year":2024,"journal":"Sports medicine (Auckland, N.Z.), 54(11), 2865-2888","doi":"10.1007/s40279-024-02079-0","pmid":"39060741","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07861","title":"Reduction in systemic muscle stress markers after exercise-induced muscle damage following concurrent training and supplementation with specific collagen peptides - a randomized controlled trial.","authors":"Bischof, Kevin; Stafilidis, Savvas; Bundschuh, Larissa; Oesser, Steffen; Baca, Arnold; König, Daniel","year":2024,"journal":"Frontiers in nutrition, 11, 1384112","doi":"10.3389/fnut.2024.1384112","pmid":"38590831","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07862","title":"Understanding of probiotic origin antimicrobial peptides: a sustainable approach ensuring food safety.","authors":"Bisht, Vishakha; Das, Biki; Hussain, Ajmal; Kumar, Vinod; Navani, Naveen Kumar","year":2024,"journal":"NPJ science of food, 8(1), 67","doi":"10.1038/s41538-024-00304-8","pmid":"39300165","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07863","title":"Exploring Hypoglycemic Ketoacidosis in Nondiabetic Patients on Tirzepatide: Is Starvation the Culprit?","authors":"Bitar, Zouheir; Abdelraouf, Heba M; Maig, Rania A; Maadarani, Ossama; Bitar, Zainab Zouheir; Dashti, Hussien","year":2024,"journal":"The American journal of case reports, 25, e946133","doi":"10.12659/AJCR.946133","pmid":"39686534","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07864","title":"Dulaglutide and Glomerular Hyperfiltration, Proteinuria, and Albuminuria in Youth With Type 2 Diabetes: Post Hoc Analysis of the AWARD-PEDS Study.","authors":"Bjornstad, Petter; Arslanian, Silva A; Hannon, Tamara S; Zeitler, Philip S; Francis, Jennie L; Curtis, Alexandra M; Turfanda, Ibrahim; Cox, David A","year":2024,"journal":"Diabetes care, 47(9), 1617-1621","doi":"10.2337/dc24-0322","pmid":"38954432","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Over 26 weeks, dulaglutide reduced eGFR by 5.8 mL/min/1.73 m² versus only 0.1 in the placebo group (p=0.016). This decrease was concentrated in participants who started with glomerular hyperfiltration — a paradoxically high filtration rate that signals early kidney damage.\n\nCritically, the prevalence of both glomerular hyperfiltration and proteinuria (protein in the urine) decreased with dulaglutide but increased with placebo (p=0.014 and p=0.004, respectively). In the context of diabetic kidney disease, a reduction in hyperfiltration is considered protective — it means the kidneys are working under less stress, potentially slowing progression to irreversible damage.","whyItMatters":"Type 2 diabetes in youth is a growing epidemic, and these young patients develop kidney disease faster and more severely than adults with the same condition. Glomerular hyperfiltration is one of the earliest detectable signs of kidney damage, often appearing before any symptoms. Finding that a GLP-1 agonist can normalize this early pathology in teenagers could mean the difference between kidney health and kidney failure decades later — if the protective effect proves durable.","specificNumbers":"","methodology":"This was a post hoc analysis of kidney laboratory data from the AWARD-PEDS study, a completed placebo-controlled trial of dulaglutide for blood sugar control in 154 youth (ages 10-18) with type 2 diabetes. Researchers examined changes in eGFR, glomerular hyperfiltration prevalence, proteinuria, and albuminuria from baseline to 26 weeks.","limitations":"This was a post hoc analysis, meaning kidney outcomes were not the original primary endpoint, and the study wasn't powered to detect kidney differences. The sample size of 154 is small for kidney outcome conclusions. The 26-week duration is too short to determine whether the kidney benefits translate to long-term prevention of diabetic kidney disease. The eGFR decrease could reflect hemodynamic effects rather than structural kidney protection. The impact on hard kidney endpoints remains unclear."},{"rthcId":"RPEP-07865","title":"Venom-inspired somatostatin receptor 4 (SSTR4) agonists as new drug leads for peripheral pain conditions.","authors":"Bjørn-Yoshimoto, Walden E; Ramiro, Iris Bea L; Koch, Thomas Lund; Engholm, Ebbe; Yeung, Ho Yan; Sørensen, Kasper K; Goddard, Carolyn M; Jensen, Kathrine L; Smith, Nicholas A; Martin, Laurent F; Smith, Brian J; Madsen, Kenneth L; Jensen, Knud J; Patwardhan, Amol; Safavi-Hemami, Helena","year":2024,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2024.04.29.591104","pmid":"38746149","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07866","title":"SPECT/CT Image-Derived Absorbed Dose to Red Marrow Correlates with Hematologic Toxicity in Patients Treated with [177Lu]Lu-DOTATATE.","authors":"Blakkisrud, Johan; Peterson, Avery B; Wildermann, Scott J; Kingkiner, Griffen; Wong, Ka Kit; Wang, Chang; Frey, Kirk A; Stokke, Caroline; Dewaraja, Yuni K","year":2024,"journal":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 65(5), 753-760","doi":"10.2967/jnumed.123.266843","pmid":"38548350","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07867","title":"Once-Weekly Semaglutide in Persons with Obesity and Knee Osteoarthritis.","authors":"Bliddal, Henning; Bays, Harold; Czernichow, Sébastien; Uddén Hemmingsson, Joanna; Hjelmesæth, Jøran; Hoffmann Morville, Thomas; Koroleva, Anna; Skov Neergaard, Jesper; Vélez Sánchez, Patricia; Wharton, Sean; Wizert, Alicja; Kristensen, Lars E","year":2024,"journal":"The New England journal of medicine, 391(17), 1573-1583","doi":"10.1056/NEJMoa2403664","pmid":"39476339","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07868","title":"Rapid elucidation of agonist-driven regulation of the neurokinin 1 receptor using a GPCR phosphorylation immunoassay.","authors":"Blum, Nina K; Schaffner, Anne; Drube, Julia; Nagel, Falko; Reinscheid, Rainer K; Hoffmann, Carsten; Schulz, Stefan","year":2024,"journal":"European journal of pharmacology, 973, 176587","doi":"10.1016/j.ejphar.2024.176587","pmid":"38642667","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07869","title":"Dose-response effects on HbA1c and bodyweight reduction of survodutide, a dual glucagon/GLP-1 receptor agonist, compared with placebo and open-label semaglutide in people with type 2 diabetes: a randomised clinical trial.","authors":"Blüher, Matthias; Rosenstock, Julio; Hoefler, Josef; Manuel, Raymond; Hennige, Anita M","year":2024,"journal":"Diabetologia, 67(3), 470-482","doi":"10.1007/s00125-023-06053-9","pmid":"38095657","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Survodutide produced dose-dependent HbA1c reductions up to -1.71% (DG3, 1.8 mg weekly) and weight loss up to -8.7% (DG6, 1.8 mg twice weekly) over 16 weeks. At lower doses, survodutide matched semaglutide for HbA1c reduction (-1.46% vs. -1.47%). At higher doses, survodutide produced significantly greater weight loss than semaglutide (-8.7% vs. -5.3%). Gastrointestinal adverse events were the most common side effects, occurring in 77.8% of survodutide-treated participants versus 52% with semaglutide and 52.5% with placebo. A clear dose-response relationship was observed for both efficacy and adverse events.","whyItMatters":"The addition of glucagon receptor agonism to GLP-1 signaling is a fundamentally different strategy from tirzepatide's GLP-1/GIP approach. Glucagon promotes energy expenditure and fat breakdown, which may explain survodutide's superior weight loss. This trial provides the first head-to-head data showing a dual glucagon/GLP-1 agonist outperforming semaglutide for weight loss in diabetic patients, supporting the glucagon agonism approach as a viable path to next-generation obesity treatment.","specificNumbers":"","methodology":"Phase II, multicentre, randomized, double-blind, parallel-group, placebo-controlled trial with an open-label semaglutide comparator arm. 413 participants aged 18-75 with type 2 diabetes (HbA1c 7.0-10.0%), BMI 25-50 kg/m², on background metformin. Six survodutide dose groups (0.3-2.7 mg weekly or 1.2-1.8 mg twice weekly), one semaglutide arm (up to 1.0 mg weekly), and one placebo arm. Primary endpoint: HbA1c change at 16 weeks. Key secondary endpoint: bodyweight change at 16 weeks.","limitations":"This was a 16-week Phase II trial — too short to assess long-term efficacy, durability, or cardiovascular outcomes. The semaglutide arm was open-label (not blinded), introducing potential bias. The semaglutide dose was capped at 1.0 mg (not the 2.4 mg dose approved for obesity). GI adverse events were notably higher with survodutide, which could limit real-world adherence. The trial was funded by Boehringer Ingelheim, the manufacturer of survodutide."},{"rthcId":"RPEP-07870","title":"Exploring the Impact of Semaglutide on Cognitive Function and Anxiety-Related Behaviors in a Murine Model of Alzheimer's Disease.","authors":"Boboc, Ianis Kevyn Stefan; Dumitrelea, Petrica-Daniel; Meca, Andreea Daniela; Mititelu-Tartau, Liliana; Bogdan, Maria","year":2024,"journal":"Biomedicines, 12(12)","doi":"10.3390/biomedicines12122689","pmid":"39767596","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07871","title":"Neuroendocrine Tumors: Beta Labeled Radiopeptides.","authors":"Bodei, Lisa; Jayaprakasam, Vetri Sudar; Ying Wong, Bernadette Zhi; Aparici, Carina Mari","year":2024,"journal":"PET clinics, 19(3S), e1-e11","doi":"10.1016/j.cpet.2024.06.003","pmid":"40199623","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"PRRT using lutetium-177-labeled somatostatin analogs has become the dominant form of peptide-targeted radiation therapy for neuroendocrine tumors, replacing earlier yttrium-90-based approaches. The treatment achieves significant tumor control and symptom relief in patients with somatostatin receptor-positive neuroendocrine tumors.\n\nHowever, as with other systemic therapies, treatment responses are relatively short-lived. The field is now focused on developing new peptides and treatment strategies, with a critical emphasis on individualizing therapy through patient-specific dosimetry — calculating radiation doses to both tumors and healthy organs — and understanding tissue-level radiosensitivity.","whyItMatters":"Neuroendocrine tumors are relatively rare cancers that can be difficult to treat with conventional therapies. PRRT represents one of the most successful examples of peptide-targeted therapy in oncology, using the tumor's own receptor biology against it. As the field moves toward personalized dosimetry, PRRT could become more effective and safer, potentially extending remissions and reducing side effects.","specificNumbers":"","methodology":"This is a review article that synthesizes the current state of PRRT for neuroendocrine tumors. The authors survey the evolution from yttrium-90 to lutetium-177 peptides, assess clinical outcomes, and discuss emerging strategies for treatment optimization including personalized dosimetry.","limitations":"As a review article, this paper synthesizes existing evidence rather than presenting new experimental data. The abstract does not detail specific response rates, survival data, or comparative outcomes between yttrium-90 and lutetium-177 formulations. The short-lived nature of responses is acknowledged but specific durations are not provided."},{"rthcId":"RPEP-07872","title":"Endogenous opiates and behavior: 2023.","authors":"Bodnar, Richard J","year":2024,"journal":"Peptides, 179, 171268","doi":"10.1016/j.peptides.2024.171268","pmid":"38943841","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07873","title":"Peptide receptor radionuclide therapy for ectopic Cushing's syndrome caused by metastatic neuroendocrine neoplasms.","authors":"Boehm, Emma; Hung, Terry; Akhurst, Tim; Alipour, Ramin; Chiang, Cherie; Hicks, Rodney J; Hofman, Michael S; Ravi Kumar, Aravind S; Sachithanandan, Nirupa; Saghebi, Javad; Michael, Michael; Kong, Grace","year":2024,"journal":"Endocrine oncology (Bristol, England), 4(1), e240013","doi":"10.1530/EO-24-0013","pmid":"39649117","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07874","title":"Efficacy of Racecadotril in a Patient Affected by a Therapy-Refractory VIPoma and Carcinoid Syndrome.","authors":"Boesenkoetter, Jannes; Ellrichmann, Ina; Konukiewitz, Björn; Ellrichmann, Mark; Schulte, Dominik M","year":2024,"journal":"JCEM case reports, 2(10), luae177","doi":"10.1210/jcemcr/luae177","pmid":"39351119","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07875","title":"Pharmacokinetics and Safety of Atogepant Co-administered with Quinidine Gluconate in Healthy Participants: A Phase 1, Open-Label, Drug-Drug Interaction Study.","authors":"Boinpally, Ramesh; Borbridge, Lisa; Wangsadipura, Veronica","year":2024,"journal":"Clinical pharmacology in drug development, 13(8), 930-937","doi":"10.1002/cpdd.1407","pmid":"38702918","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Co-administration of atogepant with quinidine gluconate resulted in no significant change in atogepant's peak plasma concentration. The overall systemic exposure (AUC) of atogepant increased by approximately 25%, but this increase was not considered clinically relevant.\n\nAtogepant did not alter quinidine's mean plasma concentration at steady state. The incidence of treatment-emergent adverse events was highest when quinidine gluconate was given alone (42.4%), primarily driven by QT prolongation. Most adverse events were mild and resolved within 1-2 days. The modest exposure increase was attributed to quinidine's inhibition of CYP2D6 and P-gp, both minor contributors to atogepant clearance.","whyItMatters":"Migraine patients often take multiple medications, making drug interaction data essential for safe prescribing. This study provides reassurance that atogepant can be safely combined with drugs that inhibit P-gp and CYP2D6 pathways without needing dose adjustments — important practical information for clinicians managing patients on complex medication regimens.","specificNumbers":"","methodology":"This was a phase 1, open-label drug-drug interaction study in 33 healthy adult participants. Researchers measured atogepant blood levels when given alone and when co-administered with quinidine gluconate, comparing pharmacokinetic parameters including peak concentration (Cmax) and total exposure (AUC). Safety was assessed through monitoring of adverse events.","limitations":"The study was conducted in healthy adults, not migraine patients who may have different metabolic profiles or be taking additional medications. The sample size of 33 participants is small. The open-label design means neither participants nor researchers were blinded. Only short-term co-administration was assessed, so long-term interaction effects remain unknown."},{"rthcId":"RPEP-07876","title":"Effect of a High-Fat Meal on the Pharmacokinetics of an Immediate Release Atogepant Tablet.","authors":"Boinpally, Ramesh R; Trugman, Joel M","year":2024,"journal":"Clinical pharmacology in drug development, 13(11), 1212-1218","doi":"10.1002/cpdd.1451","pmid":"38993134","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07877","title":"In vivo overexpression of the avian interleukin-17 in a necrotic enteritis disease model modulates the expression of antimicrobial peptides in the small intestine of broilers.","authors":"Boodhoo, Nitish; St-Denis, Myles; Zheng, Jiayu; Gupta, Bhavya; Sharif, Shayan","year":2024,"journal":"Cytokine, 183, 156749","doi":"10.1016/j.cyto.2024.156749","pmid":"39236431","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07878","title":"Drug effects on neuropeptides and their receptors: Big hopes but moderate success in the treatment of chronic pain.","authors":"Borbély, Éva; Pethő, Gábor","year":2024,"journal":"Current opinion in pharmacology, 77, 102474","doi":"10.1016/j.coph.2024.102474","pmid":"39121555","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07879","title":"Neuropeptide therapeutics to repress lateral septum neurons that disable sociability in an autism mouse model.","authors":"Borie, Amélie M; Dromard, Yann; Chakraborty, Prabahan; Fontanaud, Pierre; Andre, Emilie M; François, Amaury; Colson, Pascal; Muscatelli, Françoise; Guillon, Gilles; Desarménien, Michel G; Jeanneteau, Freddy","year":2024,"journal":"Cell reports. Medicine, 5(11), 101781","doi":"10.1016/j.xcrm.2024.101781","pmid":"39423809","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07880","title":"naRNA-LL37 composite DAMPs define sterile NETs as self-propagating drivers of inflammation.","authors":"Bork, Francesca; Greve, Carsten L; Youn, Christine; Chen, Sirui; N C Leal, Vinicius; Wang, Yu; Fischer, Berenice; Nasri, Masoud; Focken, Jule; Scheurer, Jasmin; Engels, Pujan; Dubbelaar, Marissa; Hipp, Katharina; Zalat, Baher; Szolek, Andras; Wu, Meng-Jen; Schittek, Birgit; Bugl, Stefanie; Kufer, Thomas A; Löffler, Markus W; Chamaillard, Mathias; Skokowa, Julia; Kramer, Daniela; Archer, Nathan K; Weber, Alexander N R","year":2024,"journal":"EMBO reports, 25(7), 2914-2949","doi":"10.1038/s44319-024-00150-5","pmid":"38783164","tags":[],"studyType":"basic-research","evidenceStrength":"moderate","keyFinding":"The antimicrobial peptide LL-37 and RNA from neutrophil extracellular traps (NETs) form a composite 'damage signal' (DAMP) that triggers a self-amplifying cycle of inflammation. This naRNA-LL37 complex stimulates fresh neutrophils to release more NETs via a TLR8–NLRP3 inflammasome pathway, and causes skin cells (keratinocytes) to express psoriasis-related genes (IL17, IL36) through NOD2-RIPK signaling.\n\nCritically, the naRNA-LL37 DAMP is pre-stored in resting neutrophil granules — meaning it's ready to go before any infection occurs. In live mice, it drove temporary skin inflammation that was dramatically reduced when RNA-sensing was genetically eliminated. Under normal conditions, the signal is self-limiting, but when NET release is dysregulated (as in psoriasis), it creates a runaway inflammatory loop.","whyItMatters":"This study reveals a new mechanism by which the cathelicidin peptide LL-37 drives chronic inflammation in diseases like psoriasis, atherosclerosis, and arthritis. By showing that LL-37 complexed with RNA creates a self-amplifying inflammatory cycle, it identifies a potential therapeutic target — blocking RNA sensing could break the cycle and treat NET-driven inflammatory diseases.","specificNumbers":"naRNA-LL37 is pre-stored in neutrophil granules · Signals via TLR8 + NLRP3 inflammasome · Keratinocyte activation via NOD2-RIPK · In vivo skin inflammation ablated by genetic knockout of RNA sensing","methodology":"Multi-approach study combining in vitro experiments with human neutrophils and keratinocytes, and in vivo mouse models. Researchers characterized the naRNA-LL37 composite DAMP, identified signaling pathways (TLR8–NLRP3 in neutrophils, NOD2-RIPK in keratinocytes), demonstrated pre-storage in neutrophil granules, and used genetic ablation of RNA sensing in mice to confirm the pathway's role in skin inflammation.","limitations":"Mouse models of skin inflammation may not fully recapitulate human psoriasis. The study demonstrates the pathway exists but doesn't quantify its relative contribution compared to other inflammatory drivers in psoriasis patients. Clinical translation — whether blocking RNA sensing would be safe and effective as a therapy — is not addressed."},{"rthcId":"RPEP-07881","title":"Quantification of the effect of GLP-1R agonists on body weight using in vitro efficacy information: An extension of the Hall body composition model.","authors":"Bosch, Rolien; Sijbrands, Eric J G; Snelder, Nelleke","year":2024,"journal":"CPT: pharmacometrics & systems pharmacology, 13(9), 1488-1502","doi":"10.1002/psp4.13183","pmid":"38867373","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07882","title":"H3K27M neoepitope vaccination in diffuse midline glioma induces B and T cell responses across diverse HLA loci of a recovered patient.","authors":"Boschert, Tamara; Kromer, Kristina; Lerner, Taga; Lindner, Katharina; Haltenhof, Gordon; Tan, Chin Leng; Jähne, Kristine; Poschke, Isabel; Bunse, Lukas; Eisele, Philipp; Grassl, Niklas; Mildenberger, Iris; Sahm, Katharina; Platten, Michael; Lindner, John M; Green, Edward W","year":2024,"journal":"Science advances, 10(5), eadi9091","doi":"10.1126/sciadv.adi9091","pmid":"38306431","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07883","title":"Comparison of gepant effects at therapeutic plasma concentrations: connecting pharmacodynamics and pharmacokinetics.","authors":"Boucherie, Deirdre M; Dammers, Ruben; Vincent, Arnaud; Danser, A H Jan; MaassenVanDenBrink, Antoinette","year":2024,"journal":"The journal of headache and pain, 25(1), 141","doi":"10.1186/s10194-024-01846-8","pmid":"39198753","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07884","title":"A consensus statement from the Japan Diabetes Society (JDS): a proposed algorithm for pharmacotherapy in people with type 2 diabetes-2nd Edition (English version).","authors":"Bouchi, Ryotaro; Kondo, Tatsuya; Ohta, Yasuharu; Goto, Atsushi; Tanaka, Daisuke; Satoh, Hiroaki; Yabe, Daisuke; Nishimura, Rimei; Harada, Norio; Kamiya, Hideki; Suzuki, Ryo; Yamauchi, Toshimasa","year":2024,"journal":"Diabetology international, 15(3), 327-345","doi":"10.1007/s13340-024-00723-8","pmid":"39101173","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07885","title":"Protein Hydrolysis as a Way to Valorise Squid-Processing Byproducts: Obtaining and Identification of ACE, DPP-IV and PEP Inhibitory Peptides.","authors":"Bougatef, Hajer; Sila, Assaad; Bougatef, Ali; Martínez-Alvarez, Oscar","year":2024,"journal":"Marine drugs, 22(4)","doi":"10.3390/md22040156","pmid":"38667773","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07886","title":"Gut hormones and bone homeostasis: potential therapeutic implications.","authors":"Bouvard, Béatrice; Mabilleau, Guillaume","year":2024,"journal":"Nature reviews. Endocrinology, 20(9), 553-564","doi":"10.1038/s41574-024-01000-z","pmid":"38858581","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07887","title":"Tirzepatide Improved Health-Related Quality of Life Compared with Insulin Lispro in Basal Insulin-Treated Adults with Type 2 Diabetes and Inadequate Glycaemic Control: A Randomised Controlled Phase 3b Trial (SURPASS-6).","authors":"Boye, Kristina Secnik; Poon, Jiat Ling; Landó, Laura Fernández; Sapin, Hélène; Huh, Ruth; Wang, Mianbo; Williamson, Suzanne; Patel, Hiren","year":2024,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 15(9), 2039-2059","doi":"10.1007/s13300-024-01620-8","pmid":"39008236","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07888","title":"Liraglutide Impacts Iron Homeostasis in a Murine Model of Hereditary Hemochromatosis.","authors":"Bozadjieva-Kramer, Nadejda; Shin, Jae Hoon; Blok, Neil B; Jain, Chesta; Das, Nupur K; Polex-Wolf, Joseph; Knudsen, Lotte Bjerre; Shah, Yatrik M; Seeley, Randy J","year":2024,"journal":"Endocrinology, 165(9)","doi":"10.1210/endocr/bqae090","pmid":"39045670","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07889","title":"The impact of glucagon and exenatide on oxidative stress levels and antioxidative enzyme expression in in vitro induced steatosis in HepG2 cell culture.","authors":"Bołdys, Aleksandra; Bułdak, Łukasz; Skudrzyk, Estera; Machnik, Grzegorz; Okopień, Bogusław","year":2024,"journal":"Endokrynologia Polska, 75(4), 419-427","doi":"10.5603/ep.99891","pmid":"39279311","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Exenatide monotherapy reduced lipid accumulation in steatotic HepG2 cells by 25%. Combined glucagon and exenatide treatment significantly reduced markers of oxidative stress: reactive oxygen species (ROS) decreased by 24% and malondialdehyde (MDA, a lipid peroxidation marker) by 21%.\n\nThe oxidative stress reduction was associated with increased expression of two antioxidant enzymes — superoxide dismutase (SOD) and glutathione peroxidase (GPx) — but not catalase (Cat). This suggests dual GLP-1 and glucagon receptor activation enhances the cell's antioxidant defense capacity.","whyItMatters":"Fatty liver disease affects roughly 25% of the global population and can progress to liver inflammation, scarring, and even liver failure. Current treatment options are limited. The finding that combined GLP-1 and glucagon receptor activation reduces oxidative stress — a key driver of disease progression — provides mechanistic support for dual-agonist peptide drugs (like survodutide and other GLP-1/glucagon co-agonists) that are currently in clinical trials for MASLD.","specificNumbers":"","methodology":"Steatosis (fat accumulation) was induced in HepG2 hepatoma cells in vitro. Cells were then treated with exenatide (GLP-1 RA), glucagon, or the combination. Oxidative stress was assessed by measuring reactive oxygen species and malondialdehyde levels. Expression of three antioxidant enzymes (SOD, GPx, Cat) was quantified. Lipid accumulation was measured to assess the fat-reducing effect of treatment.","limitations":"This is an in vitro study using a hepatoma cell line (HepG2), which may not fully represent normal liver cell behavior. The fat overload model is simplified compared to the complex metabolic environment of MASLD in living organisms. Specific doses of exenatide and glucagon used are not detailed in the abstract. No animal or human data are provided. The catalase non-response remains unexplained."},{"rthcId":"RPEP-07890","title":"Expression of somatostatin receptors in hemangioblastomas associated with von Hippel-Lindau disease as a novel diagnostic, therapeutic, and follow-up opportunity: A case report and literature review.","authors":"Brabo, Eloá Pereira; de Almeida, Sergio Altino; Rafful, Patrícia Piazza; Rosado-de-Castro, Paulo Henrique; Vieira Neto, Leonardo","year":2024,"journal":"Archives of endocrinology and metabolism, 68, e230181","doi":"10.20945/2359-4292-2023-0181","pmid":"38788146","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Peptide-receptor radionuclide imaging with 68Ga-DOTATOC identified increased somatostatin receptor expression in a suprasellar hemangioblastoma in a VHL patient. The same scan revealed multiple pancreatic neuroendocrine tumors and bilateral pheochromocytomas.\n\nAfter one year of treatment with lanreotide (a somatostatin analog), repeat 68Ga-DOTATOC imaging showed decreased radiotracer uptake by the hemangioblastoma, consistent with a metabolic response. This is significant because no systemic therapy has previously shown a response in VHL-associated hemangioblastomas, and somatostatin receptor expression in these tumors had only recently been reported in the literature.","whyItMatters":"VHL disease affects approximately 1 in 36,000 people, and hemangioblastomas are among its most debilitating manifestations — they can occur in the brain, spinal cord, and retina. Surgery is currently the only option, but tumors frequently recur and multiply over time. The discovery that these tumors express somatostatin receptors opens three opportunities: using peptide-receptor imaging for better diagnosis and monitoring, treating with somatostatin analogs like lanreotide (already FDA-approved), and potentially using peptide receptor radionuclide therapy (PRRT) for more aggressive disease.","specificNumbers":"","methodology":"This is a single case report with literature review. The patient underwent MRI for tumor detection and 68Ga-DOTATOC PET/CT for somatostatin receptor imaging before and after 12 months of lanreotide therapy. Treatment response was assessed by comparing radiotracer uptake between baseline and follow-up imaging.","limitations":"This is a single case report — the lowest level of clinical evidence. Decreased radiotracer uptake suggests metabolic response but doesn't necessarily mean tumor shrinkage or clinical benefit. No imaging measurement of tumor size change was reported. One year of follow-up is short for a chronic condition like VHL. The response may not be generalizable to other VHL patients or hemangioblastomas in different locations. The concurrent presence of neuroendocrine tumors made this patient an unusual case."},{"rthcId":"RPEP-07891","title":"Are anti-calcitonin gene-related peptide monoclonal antibodies effective in treating migraine aura? A pilot prospective observational cohort study.","authors":"Braca, Simone; Miele, Angelo; Stornaiuolo, Antonio; Cretella, Gennaro; De Simone, Roberto; Russo, Cinzia Valeria","year":2024,"journal":"Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 45(4), 1655-1660","doi":"10.1007/s10072-023-07241-6","pmid":"38091211","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07892","title":"Reversible bilateral central scotoma under scotopic conditions associated with oral semaglutide.","authors":"Bracha, Peter; Johnson, William; Chu, Sabrina; Davison, James","year":2024,"journal":"American journal of ophthalmology case reports, 36, 102121","doi":"10.1016/j.ajoc.2024.102121","pmid":"39175932","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A 72-year-old male developed bilateral, incongruent central scotomata (blind spots) under scotopic (low-light) conditions 17 days after initiating 3.0 mg daily oral semaglutide. The scotoma started in the right eye and expanded over several days before appearing in the left eye. Symptoms were only present in dim light and absent in daylight or artificial lighting. All symptoms completely resolved within 2 days of medication discontinuation. Comprehensive ophthalmologic evaluation including macular OCT, fundus photography, fundus autofluorescence, and Humphrey visual field testing revealed no structural abnormalities.","whyItMatters":"Semaglutide is one of the most widely prescribed medications globally for diabetes and weight loss. As millions of people take this GLP-1 receptor agonist, identifying even rare side effects is important for patient safety. This is the first reported case of scotopic central scotomata associated with semaglutide, and the rapid reversibility is clinically reassuring but warrants awareness.","specificNumbers":"","methodology":"This is a single case report. The patient — himself a board-certified ophthalmologist — self-reported symptoms and underwent a complete ophthalmologic evaluation after symptom resolution. The temporal relationship between semaglutide initiation, symptom onset, drug discontinuation, and symptom resolution was documented.","limitations":"This is a single case report — the lowest level of clinical evidence. Causation cannot be definitively established from temporal association alone. The patient was unique in being an ophthalmologist who could precisely describe visual symptoms. The mechanism is unknown — no structural changes were found on imaging. It's possible this was coincidental or related to another factor."},{"rthcId":"RPEP-07893","title":"Clinical Manifestations of Semaglutide Overdose: A Case Study.","authors":"Branch, Matthew R; Amador, Isabella E; Tardif, Irina; Patel, Kruti K; Lewis, Daniel A","year":2024,"journal":"Journal of psychiatric practice, 30(6), 444-446","doi":"10.1097/PRA.0000000000000824","pmid":"39655973","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The patient experienced only mild and self-limiting symptoms following intentional semaglutide overdose. The specific overdose amount was not detailed in the abstract, but the clinical course was benign, requiring no specific antidote or intensive medical intervention.\n\nThis finding is notable because semaglutide overdose data is extremely limited in the medical literature, yet the drug is now one of the most widely prescribed medications globally. The case contributes to the understanding of semaglutide's safety margin — the gap between therapeutic and dangerous doses — which appears to be substantial.","whyItMatters":"With semaglutide prescriptions reaching unprecedented levels worldwide for both diabetes and weight loss, understanding what happens in overdose is a critical safety question. Emergency physicians, psychiatrists, and poison control centers need to know the expected clinical course when patients present with semaglutide overdose — whether accidental (dosing errors) or intentional. This case provides early evidence that large doses produce manageable symptoms, which is reassuring but requires more data to confirm.","specificNumbers":"","methodology":"This is a single case report documenting the clinical presentation, course, and outcome of an intentional semaglutide overdose in a psychiatric setting. Standard clinical monitoring was used to track symptoms and vital signs.","limitations":"This is a single case report with no details on the specific amount of semaglutide injected, making it impossible to characterize a dose-toxicity relationship. One benign outcome does not guarantee safety in all overdose scenarios — different amounts, patient health conditions, or concurrent medications could produce different results. The case does not address overdose with oral semaglutide or other GLP-1 agonists. Long-term sequelae of the overdose, if any, were not reported."},{"rthcId":"RPEP-07894","title":"Biomarkers of Hemodynamic Congestion in Heart Failure.","authors":"Brann, Alison; Selko, Sean; Krauspe, Ethan; Shah, Kevin","year":2024,"journal":"Current heart failure reports, 21(6), 541-553","doi":"10.1007/s11897-024-00684-8","pmid":"39298084","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07895","title":"Social Media as Pharmacovigilance: The Potential for Patient Reports to Inform Clinical Research on Glucagon-Like Peptide 1 (GLP-1) Receptor Agonists for Substance Use Disorders.","authors":"Bremmer, Michael P; Hendershot, Christian S","year":2024,"journal":"Journal of studies on alcohol and drugs, 85(1), 5-11","doi":"10.15288/jsad.23-00318","pmid":"37917019","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07896","title":"Tear neuropeptide Y as a non-invasive marker of peripheral microvascular complications in type 1 diabetes.","authors":"Britten-Jones, Alexis Ceecee; Wu, Mengliang; Roberts, Leslie J; MacIsaac, Richard J; Jiao, Haihan; Craig, Jennifer P; Chinnery, Holly R; Downie, Laura E","year":2024,"journal":"The ocular surface, 34, 309-316","doi":"10.1016/j.jtos.2024.08.011","pmid":"39153598","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07897","title":"Do dried blood spots have the potential to support result management processes in routine sports drug testing?-Part 3: LC-MS/MS-based peptide analysis for dried blood spot sampling time point estimation.","authors":"Brockbals, Lana; Thomas, Andreas; Schneider, Tom D; Kraemer, Thomas; Steuer, Andrea E; Thevis, Mario","year":2024,"journal":"Drug testing and analysis, 16(8), 792-800","doi":"10.1002/dta.3463","pmid":"36829300","tags":["anti-doping","peptide-detection"],"studyType":"original-research","evidenceStrength":"moderate","keyFinding":"Researchers developed a targeted LC-MS/MS method to analyze peptide markers in dried blood spot (DBS) samples that can estimate when a blood sample was collected. They tracked peptide changes across 10 volunteers over 3 months at three storage temperatures (room temperature, 4 degrees C, and -20 degrees C).\n\nTwo peptide area ratios — calculated from peptides originating from the same parent protein — significantly increased after 28 days of room temperature storage. These ratios serve as potential time-since-collection markers, which could verify that athletes actually collected their DBS samples when they claimed to during remote self-sampling for anti-doping purposes.","whyItMatters":"The World Anti-Doping Agency recently approved dried blood spots for routine doping control. This opens the door to athletes collecting their own samples remotely — but that creates a trust problem: how do you verify when the sample was actually taken? This study addresses that gap by identifying peptide markers that change predictably over time, essentially creating a biological timestamp. If validated further, this could make remote anti-doping monitoring more reliable and harder to cheat.","specificNumbers":"n=10 volunteers · 3-month monitoring period · 12 time points (0–91 days) · 3 storage temperatures (RT, 4°C, −20°C) · 2 peptide ratios significant at 28 days RT","methodology":"Ten volunteers provided dried blood spot samples that were stored for up to 91 days at three temperatures (room temperature, 4°C, and -20°C). Samples were collected at 12 time points. Using a targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, researchers measured changes in specific peptide sequences over time. They created ratios of two peptides from the same parent protein and tracked how these ratios changed with storage duration and temperature. Method validation included intraday precision, carryover testing, and sample extract stability.","limitations":"Small sample size of only 10 volunteers, which may not capture the full range of biological variability. The significant peptide ratio changes were only observed at room temperature storage after 28 days — the method may not work for samples stored at cooler temperatures or for shorter time periods. This is a proof-of-concept study; large-scale validation in real doping control scenarios hasn't been done yet."},{"rthcId":"RPEP-07898","title":"Emerging pharmacological targets for alcohol use disorder.","authors":"Brockway, Dakota F; Crowley, Nicole A","year":2024,"journal":"Alcohol (Fayetteville, N.Y.), 121, 103-114","doi":"10.1016/j.alcohol.2024.07.007","pmid":"39069210","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07899","title":"Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may reduce the risk of developing cancer-related lymphedema following axillary lymph node dissection (ALND).","authors":"Brown, Stav; Tadros, Audree B; Montagna, Giacomo; Bell, Tajah; Crowley, Fionnuala; Gallagher, Emily J; Dayan, Joseph H","year":2024,"journal":"Frontiers in pharmacology, 15, 1457363","doi":"10.3389/fphar.2024.1457363","pmid":"39318780","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07900","title":"Higher Preoperative Serum Neuropeptide Y Concentration May Be Associated with a Better Prognosis After Surgery for Colorectal Cancer.","authors":"Budzyński, Jacek; Czarnecki, Damian; Ziółkowski, Marcin; Szukay, Beata; Mysiak, Natalia; Staniewska, Agata; Michalska, Małgorzata; Żekanowska, Ewa; Tojek, Krzysztof","year":2024,"journal":"Nutrients, 16(22)","doi":"10.3390/nu16223825","pmid":"39599612","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07901","title":"Effectiveness and safety of once-weekly semaglutide: findings from the SEMACOL-REAL retrospective multicentric observational study in Colombia.","authors":"Buenaventura-Collazos, Daisy C; García-Ramos, Andrés F; Balcázar-Valencia, Carlos M; Aguilar-Londoño, Carolina; Coronel-Restrepo, Nicolás; Monsalve-Arango, Claudia Y; Cuesta-Castro, Diana P; Ramírez-Rincón, Alex","year":2024,"journal":"Frontiers in endocrinology, 15, 1372992","doi":"10.3389/fendo.2024.1372992","pmid":"38982987","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07902","title":"Outcomes, unmet needs, and challenges in the management of patients who withdraw from anti-CGRP monoclonal antibodies: A prospective cohort study.","authors":"Burgalassi, Andrea; Romozzi, Marina; Vigani, Giulia; De Icco, Roberto; Raffaelli, Bianca; Boccalini, Alberto; De Cesaris, Francesco; Calabresi, Paolo; Geppetti, Pierangelo; Chiarugi, Alberto; Iannone, Luigi Francesco","year":2024,"journal":"Cephalalgia : an international journal of headache, 44(11), 3331024241273968","doi":"10.1177/03331024241273968","pmid":"39497430","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Of 472 patients treated with anti-CGRP/R monoclonal antibodies, 136 (28.8%) discontinued after an average of 9.0 months. Ineffectiveness was the primary reason (70.6%), followed by loss to follow-up (13.1%) and adverse events (7.3%). Most (77.9%) discontinued within the first year. Response rates (≥50% reduction in monthly headache days) were 30.5% at 3 months, 34.6% at 6 months, and 40.0% at 12 months — but only 16.9% were responding in their last month before discontinuation. After stopping, 48.5% started new treatment, with 67.6% of those switching to a different anti-CGRP antibody.","whyItMatters":"Understanding what happens when anti-CGRP drugs fail is critical for the ~25-30% of patients who don't respond. This study shows that switching between anti-CGRP antibodies is the most common next step — and may be rational, since different drugs target CGRP or its receptor differently. It also highlights a significant unmet need: nearly 40% of discontinuers were lost to follow-up, suggesting many patients may be left without adequate migraine care.","specificNumbers":"","methodology":"This was a prospective cohort study at the Florence Headache Center in Italy, tracking all migraine patients who discontinued anti-CGRP/R monoclonal antibody treatment. Primary outcomes were reasons for discontinuation and treatment course. Secondary outcomes included changes in monthly headache days, response rates, medication overuse, analgesic use, and MIDAS and HIT-6 disability scores at 3, 6, and 12 months.","limitations":"This is a single-center study, which may not represent all patient populations. The 39.7% lost to follow-up after discontinuation limits understanding of long-term outcomes. The study does not compare outcomes between different anti-CGRP antibodies. No biomarker analysis was performed to predict non-response, and the definition of treatment failure was clinical rather than standardized."},{"rthcId":"RPEP-07903","title":"Real-world Impact of Fremanezumab on Migraine-Related Health Care Resource Utilization in Patients with Comorbidities, Acute Medication Overuse, and/or Unsatisfactory Prior Migraine Preventive Response.","authors":"Buse, Dawn C; Krasenbaum, Lynda J; Seminerio, Michael J; Packnett, Elizabeth R; Carr, Karen; Ortega, Mario; Driessen, Maurice T","year":2024,"journal":"Pain and therapy, 13(3), 511-532","doi":"10.1007/s40122-024-00583-9","pmid":"38472655","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 3,193 eligible patients, fremanezumab initiation was associated with significant reductions in: acute medication claims (0.97 to 0.86 PPPM, p<0.001), preventive medication claims excluding fremanezumab (0.94 to 0.81 PPPM, p<0.001), outpatient visits, neurologist visits, ER visits, and other outpatient services (all p<0.001). Total migraine-related healthcare costs decreased from $541 to $490 PPPM (p=0.003). Adherence was good with mean proportion of days covered of 0.71 and persistence duration of 160.3 days at 6 months.","whyItMatters":"Migraine patients with comorbidities and failed prior treatments are the hardest and most expensive to manage. Showing that fremanezumab reduces their healthcare utilization and costs — not just in clinical trials but in real-world practice — supports its value for this difficult-to-treat population and helps justify its cost to insurers and healthcare systems.","specificNumbers":"","methodology":"Retrospective US insurance claims analysis using Merative MarketScan databases. Adults with migraine who initiated fremanezumab between September 2018 and June 2019 were included if they had ≥12 months pre-index data and ≥6 months post-index follow-up, plus qualifying comorbidities (depression, anxiety, cardiovascular disease), acute medication overuse, or unsatisfactory prior preventive response. Pre vs post comparisons assessed medication use, healthcare resource utilization, and costs.","limitations":"This is a retrospective claims study without a control group, so changes cannot be definitively attributed to fremanezumab versus natural disease fluctuation or regression to the mean. Claims data lack clinical outcomes like migraine frequency or severity. The $51 monthly cost reduction may not offset fremanezumab's drug cost. The study was funded by Teva Pharmaceuticals, the manufacturer of fremanezumab."},{"rthcId":"RPEP-07904","title":"Semaglutide versus placebo in people with obesity-related heart failure with preserved ejection fraction: a pooled analysis of the STEP-HFpEF and STEP-HFpEF DM randomised trials.","authors":"Butler, Javed; Shah, Sanjiv J; Petrie, Mark C; Borlaug, Barry A; Abildstrøm, Steen Z; Davies, Melanie J; Hovingh, G Kees; Kitzman, Dalane W; Møller, Daniél Vega; Verma, Subodh; Einfeldt, Mette Nygaard; Lindegaard, Marie L; Rasmussen, Søren; Abhayaratna, Walter; Ahmed, Fozia Z; Ben-Gal, Tuvia; Chopra, Vijay; Ezekowitz, Justin A; Fu, Michael; Ito, Hiroshi; Lelonek, Małgorzata; Melenovský, Vojtěch; Merkely, Bela; Núñez, Julio; Perna, Eduardo; Schou, Morten; Senni, Michele; Sharma, Kavita; van der Meer, Peter; Von Lewinski, Dirk; Wolf, Dennis; Kosiborod, Mikhail N","year":2024,"journal":"Lancet (London, England), 403(10437), 1635-1648","doi":"10.1016/S0140-6736(24)00469-0","pmid":"38599221","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07905","title":"Long-Term clinical efficacy of liraglutide for type 2 diabetes: real-world evidence and outcomes from Pakistan.","authors":"Butt, Muhammad Daoud; Ong, Siew Chin; Rafiq, Azra; Batool, Nighat; Saifi, Rumana; Yaseen, Samina; Kaukab, Irum; Ramzan, Basit","year":2024,"journal":"Journal of pharmaceutical policy and practice, 17(1), 2432462","doi":"10.1080/20523211.2024.2432462","pmid":"39640418","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07906","title":"Efficacy and safety of semaglutide: real-world tertiary care experience from Saudi Arabia.","authors":"Butt, Muhammad Imran; Alkhalifah, Khalid Mania; Riazuddin, Muhammad; Almuammar, Saud Mohammed; Almuammar, Salman Mohammed; Alhifthi, Ghayda Abdulkader; Ahmed, Fahad Wali; Al Hashim, Samia Mohamed; Waheed, Najeeb","year":2024,"journal":"Annals of Saudi medicine, 44(6), 361-368","doi":"10.5144/0256-4947.2024.361","pmid":"39651921","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07907","title":"An Assessment of Semaglutide Safety Based on Real World Data: From Popularity to Spontaneous Reporting in EudraVigilance Database.","authors":"Butuca, Anca; Dobrea, Carmen Maximiliana; Arseniu, Anca Maria; Frum, Adina; Chis, Adriana Aurelia; Rus, Luca Liviu; Ghibu, Steliana; Juncan, Anca Maria; Muntean, Andrei Catalin; Lazăr, Antonina Evelina; Gligor, Felicia Gabriela; Morgovan, Claudiu; Vonica-Tincu, Andreea Loredana","year":2024,"journal":"Biomedicines, 12(5)","doi":"10.3390/biomedicines12051124","pmid":"38791086","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07908","title":"Systematic Review of Left Ventricular Remodeling in Response to Hypoglycemic Medications: Assessing Changes in End-Systolic and End-Diastolic Diameters.","authors":"Buz, Bogdan-Flaviu; Negrean, Rodica Anamaria; Caruntu, Florina; Parvanescu, Tudor; Slovenski, Milena; Tomescu, Mirela Cleopatra; Arnautu, Diana-Aurora","year":2024,"journal":"Biomedicines, 12(8)","doi":"10.3390/biomedicines12081791","pmid":"39200254","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07909","title":"Correlation of the FIB-4 Liver Biomarker Score with the Severity of Heart Failure.","authors":"Buzas, Roxana; Ciubotaru, Paul; Faur, Alexandra Corina; Preda, Marius; Ardelean, Melania; Georgescu, Doina; Dumitrescu, Patrick; Lighezan, Daniel Florin; Popa, Mihaela-Diana","year":2024,"journal":"Medicina (Kaunas, Lithuania), 60(12)","doi":"10.3390/medicina60121943","pmid":"39768827","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07910","title":"Liraglutide Therapy in Obese Patients Alters Macrophage Phenotype and Decreases Their Tumor Necrosis Factor Alpha Release and Oxidative Stress Markers-A Pilot Study.","authors":"Bułdak, Łukasz; Bołdys, Aleksandra; Skudrzyk, Estera; Machnik, Grzegorz; Okopień, Bogusław","year":2024,"journal":"Metabolites, 14(10)","doi":"10.3390/metabo14100554","pmid":"39452935","tags":["glp-1-agonists","cardiovascular-health"],"studyType":"pilot-clinical-study","evidenceStrength":"preliminary","keyFinding":"Three months of liraglutide treatment in obese patients shifted their macrophages from the inflammatory M1 type toward the anti-inflammatory M2 type. This phenotype switch was accompanied by reduced TNFα release (a key inflammatory cytokine) and decreased oxidative stress markers (reactive oxygen species and malondialdehyde).\n\nThis is one of the first in vivo human studies to show that GLP-1 analogs directly alter immune cell behavior — not just in a lab dish but in actual patients. The shift toward M2 macrophages could help explain why GLP-1 drugs reduce cardiovascular events: M1 macrophages drive atherosclerotic plaque formation and instability, while M2 macrophages promote tissue repair.","whyItMatters":"Large clinical trials have shown that GLP-1 drugs like liraglutide and semaglutide significantly reduce heart attacks and strokes, but the mechanism goes beyond simple weight loss and blood sugar control. This pilot study provides a potential explanation: GLP-1 drugs may calm the immune cells (macrophages) that drive atherosclerosis. Since macrophages are central to plaque formation, instability, and rupture, switching them from inflammatory to anti-inflammatory could directly protect arteries — a 'bonus' cardiovascular effect on top of metabolic benefits.","specificNumbers":"3-month liraglutide treatment · Macrophage shift from M1 → M2 phenotype · Reduced TNFα release · Decreased ROS and malondialdehyde · Markers assessed: iNOS, arginase 1, mannose receptors, IL-1β, TNFα","methodology":"Pilot clinical study in patients with obesity treated with subcutaneous liraglutide for 3 months. Macrophages were obtained from patients before and after treatment. Researchers assessed phenotypic markers (inducible nitric oxide synthase, arginase 1, mannose receptors), proinflammatory cytokine release (IL-1β, TNFα), and oxidative stress markers (reactive oxygen species, malondialdehyde).","limitations":"This is a pilot study with a small, unspecified sample size. There was no placebo or control group — the before/after design means confounders like weight loss itself could drive the macrophage changes. The study didn't determine whether the macrophage changes translate to reduced atherosclerotic events. IL-1β changes were not specifically noted in the results. Published in a lower-impact journal (Metabolites)."},{"rthcId":"RPEP-07911","title":"Degree of hydrolysis is a poor predictor of the sensitizing capacity of whey- and casein-based hydrolysates in a Brown Norway rat model of cow's milk allergy.","authors":"Bøgh, Katrine Lindholm; Nielsen, Ditte Møller; Mohammad-Beigi, Hossein; Christoffersen, Heidi Frahm; Jacobsen, Lotte Neergaard; Norrild, Rasmus Krogh; Svensson, Birte; Schmidthaler, Klara; Szépfalusi, Zsolt; Upton, Julia; Eiwegger, Thomas; Bertelsen, Hans; Buell, Alexander Kai; Sørensen, Laila Vestergaard; Larsen, Jeppe Madura","year":2024,"journal":"Food research international (Ottawa, Ont.), 181, 114063","doi":"10.1016/j.foodres.2024.114063","pmid":"38448113","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07912","title":"Real-World Evaluation of Once-Weekly Subcutaneous Semaglutide in Patients with Type 2 Diabetes Mellitus in Spain (SEMA-RW Study).","authors":"Caballero Mateos, Irene; García de Lucas, María Dolores; Doulatram-Gamgaram, Viyey Kishore; Moreno-Moreno, Paloma; Jimenez-Millan, Ana Isabel; Botana-López, Manuel; Merino-Torres, Juan Francisco; Soto-Gónzalez, Alfonso; Fernández-García, José Carlos; Morales-Portillo, Cristóbal","year":2024,"journal":"Nutrients, 16(15)","doi":"10.3390/nu16152545","pmid":"39125424","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07913","title":"Antitumoral and Antiproliferative Potential of Synthetic Derivatives of Scorpion Peptide IsCT1 in an Oral Cavity Squamous Carcinoma Model.","authors":"Cabral, Laertty Garcia de Sousa; de Oliveira, Cyntia Silva; Oliveira, Vani Xavier; Alves, Rosely Cabette Barbosa; Poyet, Jean-Luc; Maria, Durvanei Augusto","year":2024,"journal":"Molecules (Basel, Switzerland), 29(19)","doi":"10.3390/molecules29194533","pmid":"39407463","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07914","title":"Marine Antioxidants from Marine Collagen and Collagen Peptides with Nutraceuticals Applications: A Review.","authors":"Cadar, Emin; Pesterau, Ana-Maria; Prasacu, Irina; Ionescu, Ana-Maria; Pascale, Carolina; Dragan, Ana-Maria Laura; Sirbu, Rodica; Tomescu, Cezar Laurentiu","year":2024,"journal":"Antioxidants (Basel, Switzerland), 13(8)","doi":"10.3390/antiox13080919","pmid":"39199165","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"This review catalogues the antioxidant properties of collagen peptides derived from marine sources including fish (skin, bones, scales, fins, cartilage), jellyfish, mollusks, crustaceans, and sponges. The authors found that specific amino acid sequences in marine collagen hydrolysates demonstrate significant antioxidant activity, and that the extraction method used to break down collagen into peptides affects which antioxidant properties are preserved. Marine collagen peptides from both vertebrate and invertebrate sources showed potential as natural antioxidant nutraceuticals.","whyItMatters":"The marine collagen peptide market is booming as a supplement category, and most consumers don't know where the collagen comes from or how it's processed. This review organizes the scientific evidence behind marine collagen's antioxidant claims, identifying which marine sources and extraction methods produce the most bioactive peptides. It also highlights an environmental angle — using fish processing waste (skin, scales, bones) as a source of valuable bioactive peptides rather than discarding it.","specificNumbers":"","methodology":"The authors conducted a literature review analyzing published data on marine collagen peptides with antioxidant properties. They systematized information on extraction methods (enzymatic hydrolysis and other treatments), structural characteristics of the resulting peptides, and their measured antioxidant activities across different marine species — both vertebrate (fish) and invertebrate (jellyfish, mollusks, crustaceans, sponges).","limitations":"This is a review of primarily in vitro (lab-based) antioxidant measurements. Antioxidant activity in a test tube doesn't necessarily translate to health benefits in the human body. The review doesn't systematically evaluate human clinical trial evidence for health outcomes. Extraction methods and collagen sources vary enormously, making direct comparisons difficult."},{"rthcId":"RPEP-07915","title":"Tirzepatide as a novel effective and safe strategy for treating obesity: a systematic review and meta-analysis of randomized controlled trials.","authors":"Cai, Wenting; Zhang, Ruobin; Yao, Yao; Wu, Qiuhui; Zhang, Jinping","year":2024,"journal":"Frontiers in public health, 12, 1277113","doi":"10.3389/fpubh.2024.1277113","pmid":"38356942","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 12 randomized controlled trials with 11,758 patients, tirzepatide significantly reduced BMI (mean difference -1.71, 95% CI -2.46 to -0.95), waist circumference, and body weight compared to GLP-1 receptor agonists, placebo, and insulin. Tirzepatide outperformed existing GLP-1 drugs for weight loss. Gastrointestinal side effects were the primary safety concern but overall safety was considered high.","whyItMatters":"This meta-analysis of RCTs provides the highest level of evidence that tirzepatide — a dual GIP/GLP-1 receptor agonist peptide — is more effective for weight loss than existing GLP-1 drugs alone. With obesity affecting over 650 million people worldwide, confirming tirzepatide's superiority in a large pooled analysis has major implications for treatment guidelines.","specificNumbers":"12 RCTs · n=11,758 · BMI MD -1.71 (95% CI -2.46 to -0.95) · superior to GLP-1 RAs, placebo, and insulin · GI adverse reactions noted · overall safety high","methodology":"Systematic review and meta-analysis of randomized controlled trials. Databases searched: PubMed, Cochrane Library, Embase, and Web of Science through May 2023. Twelve RCTs meeting inclusion criteria were analyzed using RevMan 5.4. Outcomes included BMI, waist circumference, body weight, and adverse events. Comparators included GLP-1 receptor agonists, placebo, and insulin.","limitations":"The abstract contains truncated statistical data, making it difficult to assess all effect sizes. The search ended in May 2023, so newer RCTs are not included. The analysis focused on short-to-medium term outcomes; long-term weight maintenance data may be limited. Heterogeneity across trials in dosing, duration, and populations may affect pooled estimates."},{"rthcId":"RPEP-07916","title":"Rational Design of a Potent Antimicrobial Peptide Based on the Active Region of a Gecko Cathelicidin.","authors":"Cai, Ying; Wang, Xingyu; Zhang, Tianyu; Yan, An; Luo, Lin; Li, Chenxi; Tian, Gengzhou; Wu, Zhongxiang; Wang, Xi; Shen, Dong; Han, Yajun; Zhang, Zhiye","year":2024,"journal":"ACS infectious diseases, 10(3), 951-960","doi":"10.1021/acsinfecdis.3c00575","pmid":"38315114","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07917","title":"Injectable self-assembling peptide hydrogel as a promising vitreous substitute.","authors":"Cai, Yuting; Xiang, Yatong; Dong, Huilei; Huang, Wenjing; Liu, Yan; Zhao, Chenguang; Yuan, Dan; Li, Yun; Shi, Junfeng","year":2024,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 376, 402-412","doi":"10.1016/j.jconrel.2024.10.016","pmid":"39401678","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The negatively charged peptide hydrogel 3E-OX demonstrated physicochemical properties closely resembling native vitreous humor, including optimal light transmittance, refractive index, molecular permeability, and viscoelasticity. In contrast, the positively charged variant (3K-OX) was less suitable.\n\nAnimal studies in rabbits confirmed the safety and biocompatibility of 3E-OX as a vitreous substitute. The researchers also introduced optical coherence tomography (OCT) for retinal microvascular detection in non-pigmented rabbits as a novel method to evaluate intraocular tamponade materials, providing more detailed assessment of retinal health after vitreous replacement.","whyItMatters":"Current vitreous substitutes (silicone oil, gas, saline) all have significant limitations — silicone oil requires a second surgery for removal and can cause complications, while gas and saline are temporary. A biocompatible, injectable peptide hydrogel that mimics natural vitreous properties could eliminate the need for removal surgery and provide a permanent, well-tolerated substitute for patients undergoing vitreoretinal surgery.","specificNumbers":"","methodology":"Researchers designed and synthesized two self-assembling peptide hydrogels with opposite charges (3K-OX positive, 3E-OX negative). In vitro characterization included light transmittance, refractive index, molecular permeability, viscoelasticity, and biocompatibility testing. In vivo studies were conducted in rabbits, using the hydrogels as vitreous substitutes after vitrectomy. Optical coherence tomography was used to evaluate retinal health and microvascular integrity in non-pigmented rabbits.","limitations":"The study was conducted in rabbits, and the long-term biocompatibility and performance in human eyes remain to be established. The observation period for animal studies was not specified in the abstract. No comparison with current clinical vitreous substitutes was described. Manufacturing scalability and regulatory pathway for a peptide hydrogel medical device were not addressed. Human clinical trials are needed before clinical adoption."},{"rthcId":"RPEP-07918","title":"Self-assembly, cytocompatibility, and interactions of desmopressin with sodium polystyrene sulfonate.","authors":"Caliari, Ana B; Bicev, Renata N; da Silva, Caroline C; de Souza, Sinval E G; da Silva, Marta G; Souza, Louise E A; de Mello, Lucas R; Hamley, Ian W; Motta, Guacyara; Degrouard, Jéril; Tresset, Guillaume; Quaresma, Alexandre J C; Nakaie, Clovis R; da Silva, Emerson R","year":2024,"journal":"Soft matter, 20(48), 9597-9613","doi":"10.1039/d4sm01125b","pmid":"39584497","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Desmopressin, a synthetic peptide analog of vasopressin, self-assembles with the polymer sodium polystyrene sulfonate (NaPSS) to form hybrid fibrillar nanostructures enriched in β-turn and β-sheet domains. When tested against breast cancer cell lines, these peptide-polymer complexes were well-tolerated by non-metastatic MCF-7 cells but showed inhibitory effects against the highly metastatic MDA-MB-231 cells, suggesting selective anticancer activity.","whyItMatters":"Desmopressin is already an FDA-approved drug used for diabetes insipidus and bleeding disorders, and there is growing interest in repurposing it as a cancer treatment. This study shows that combining it with another approved drug (NaPSS) creates nanostructures that selectively target aggressive cancer cells — a promising step toward peptide-polymer nanotherapeutics built entirely from existing medications.","specificNumbers":"","methodology":"The researchers used advanced structural imaging techniques — small-angle X-ray scattering (SAXS), cryo-electron microscopy, and atomic force microscopy with infrared nanospectroscopy — to characterize how desmopressin and NaPSS self-assemble together. They then tested the resulting complexes on two breast cancer cell lines (non-metastatic MCF-7 and metastatic MDA-MB-231) using in vitro cytotoxicity assays.","limitations":"This is an in vitro study using only two cell lines, so results cannot be directly translated to cancer treatment in humans. The selective toxicity mechanism is not fully explained. No animal models or pharmacokinetic data were included, and the long-term stability and behavior of these nanoassemblies in biological environments remain unknown."},{"rthcId":"RPEP-07919","title":"Drug-Drug Interactions Between Glucagon-Like Peptide 1 Receptor Agonists and Oral Medications: A Systematic Review.","authors":"Calvarysky, Bronya; Dotan, Idit; Shepshelovich, Daniel; Leader, Avi; Cohen, Talia Diker","year":2024,"journal":"Drug safety, 47(5), 439-451","doi":"10.1007/s40264-023-01392-3","pmid":"38273155","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07920","title":"Pre-vaccination transcriptomic profiles of immune responders to the MUC1 peptide vaccine for colon cancer prevention.","authors":"Cameron, Cheryl M; Raghu, Vineet; Richardson, Brian; Zagore, Leah L; Tamilselvan, Banumathi; Golden, Jackelyn; Cartwright, Michael; Schoen, Robert E; Finn, Olivera J; Benos, Panayiotis V; Cameron, Mark J","year":2024,"journal":"Frontiers in immunology, 15, 1437391","doi":"10.3389/fimmu.2024.1437391","pmid":"39450169","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07921","title":"Newer pharmacological interventions directed at gut hormones for obesity.","authors":"Camilleri, Michael; Acosta, Andres","year":2024,"journal":"British journal of pharmacology, 181(8), 1153-1164","doi":"10.1111/bph.16278","pmid":"37917871","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07922","title":"Evaluating the Safety and Efficacy of Capromorelin in Rhesus Macaques (Macaca mulatta).","authors":"Campellone, Gianni A; Easley, Kirk A; Jenkins, Joe B; Jean, Sherrie M","year":2024,"journal":"Journal of the American Association for Laboratory Animal Science : JAALAS, 63(3), 268-278","doi":"10.30802/AALAS-JAALAS-23-000010","pmid":"38423529","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07923","title":"Management of obesity with semaglutide or metformin in patients with antipsychotic-induced weight gain (MOSA): a non-randomised open-label pilot study.","authors":"Campforts, Bea; Drukker, Marjan; van Amelsvoort, Therese; Bak, Maarten","year":2024,"journal":"BMC psychiatry, 24(1), 865","doi":"10.1186/s12888-024-06317-7","pmid":"39616309","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07924","title":"DEFA1A3 DNA gene-dosage regulates the kidney innate immune response during upper urinary tract infection.","authors":"Canas, Jorge J; Arregui, Samuel W; Zhang, Shaobo; Knox, Taylor; Calvert, Christi; Saxena, Vijay; Schwaderer, Andrew L; Hains, David S","year":2024,"journal":"Life science alliance, 7(6)","doi":"10.26508/lsa.202302462","pmid":"38580392","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Using transgenic mice carrying the human DEFA1A3 gene, researchers demonstrated that alpha-defensin 1-3 expression and antimicrobial activity against uropathogenic E. coli (UPEC) are directly dependent on gene copy number — more copies mean stronger defense.\n\nAlpha-defensin 1-3 was expressed by both kidney neutrophils and collecting duct intercalated cells, establishing two sources of this antimicrobial peptide in the urinary tract. The defensins showed cooperative effects with other antimicrobial peptides, potentiating their bacteria-killing activity. Higher gene dosage also modulated pro-inflammatory innate immune responses, demonstrating that DEFA1A3 has both direct antimicrobial and immunomodulatory roles during UTI.","whyItMatters":"Urinary tract infections are among the most common bacterial infections, especially in children, and antibiotic resistance is a growing concern. Understanding that a patient's genetic copy number of defensin genes directly influences their susceptibility to UTIs could lead to personalized risk assessment and potentially new therapeutic strategies that boost natural antimicrobial peptide defenses rather than relying solely on antibiotics.","specificNumbers":"","methodology":"The researchers used a previously characterized transgenic mouse model carrying knock-in copies of the human DEFA1A3 gene at different copy numbers. Mice were infected with uropathogenic E. coli to induce upper urinary tract infection. The team measured alpha-defensin expression in kidney tissue (from neutrophils and collecting duct intercalated cells), assessed bacterial killing activity, evaluated cooperative effects between alpha-defensins and other antimicrobial peptides, and characterized innate immune responses as a function of gene dosage.","limitations":"The study used a transgenic mouse model, which may not perfectly replicate human kidney physiology and immune responses. The exact copy-number thresholds that affect clinical UTI outcomes in humans remain to be defined. The study focused on E. coli UTI specifically; results may differ for other uropathogens. The relative contribution of neutrophil-derived versus intercalated cell-derived defensins to overall protection was not fully quantified."},{"rthcId":"RPEP-07925","title":"Suitability and Usefulness of a Flexible Dosing Timing of Oral Semaglutide to Maximize Benefit in Clinical Practice: An Expert Panel.","authors":"Candido, Riccardo; Di Loreto, Chiara; Desenzani, Paolo; Pantanetti, Paola; Romano, Cristina; Settembrini, Silvio; Solerte, Sebastiano Bruno; Fadini, Gian Paolo","year":2024,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 15(9), 1963-1977","doi":"10.1007/s13300-024-01625-3","pmid":"39039353","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07926","title":"Thymosin Alpha 1 Plus Routine Treatment for the Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis.","authors":"Cao, Ailing; Feng, Fanchao; Zhou, Xianmei","year":2024,"journal":"Journal of the College of Physicians and Surgeons--Pakistan : JCPSP, 34(12), 1497-1507","doi":"10.29271/jcpsp.2024.12.1497","pmid":"39648386","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07927","title":"Novel Angiotensin-Converting Enzyme-Inhibitory Peptides Obtained from Trichiurus lepturus: Preparation, Identification and Potential Antihypertensive Mechanism.","authors":"Cao, Jiaming; Xiang, Boyuan; Dou, Baojie; Hu, Jingfei; Zhang, Lei; Kang, Xinxin; Lyu, Mingsheng; Wang, Shujun","year":2024,"journal":"Biomolecules, 14(5)","doi":"10.3390/biom14050581","pmid":"38785988","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07928","title":"Cryo-EM Structure of the Human Amylin 1 Receptor in Complex with CGRP and Gs Protein.","authors":"Cao, Jianjun; Belousoff, Matthew J; Danev, Radostin; Christopoulos, Arthur; Wootten, Denise; Sexton, Patrick M","year":2024,"journal":"Biochemistry, 63(9), 1089-1096","doi":"10.1021/acs.biochem.4c00114","pmid":"38603770","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07929","title":"Effects of Saponins on Lipid Metabolism: The Gut-Liver Axis Plays a Key Role.","authors":"Cao, Shixi; Liu, Mengqi; Han, Yao; Li, Shouren; Zhu, Xiaoyan; Li, Defeng; Shi, Yinghua; Liu, Boshuai","year":2024,"journal":"Nutrients, 16(10)","doi":"10.3390/nu16101514","pmid":"38794751","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07930","title":"Potential of Marine Bacterial Metalloprotease A69 in the Preparation of Peanut Peptides with Angiotensin-Converting Enzyme (ACE)-Inhibitory and Antioxidant Properties.","authors":"Cao, Wen-Jie; Liu, Rui; Zhao, Wen-Xiao; Li, Jian; Wang, Yan; Yuan, Xiao-Jie; Wang, Hui-Lin; Zhang, Yu-Zhong; Chen, Xiu-Lan; Zhang, Yu-Qiang","year":2024,"journal":"Marine drugs, 22(7)","doi":"10.3390/md22070305","pmid":"39057414","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07931","title":"Egg white-derived peptides reduced blood glucose in high-fat-diet and low-dose streptozotocin-induced type 2 diabetic mice via regulating the hepatic gluconeogenic signaling and metabolic profile.","authors":"Cao, Xinyi; Chen, Liang; Lu, Kun; Yu, Tingqing; Xia, Hui; Wang, Shaokang; Sun, Guiju; Liu, Ping; Liao, Wang","year":2024,"journal":"Food & function, 15(13), 7003-7016","doi":"10.1039/d4fo00725e","pmid":"38855929","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07932","title":"Beyond Weight Loss: the Emerging Role of Incretin-Based Treatments in Cardiometabolic HFpEF.","authors":"Capone, Federico; Nambiar, Natasha; Schiattarella, Gabriele G","year":2024,"journal":"Current opinion in cardiology, 39(3), 148-153","doi":"10.1097/HCO.0000000000001117","pmid":"38294187","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07933","title":"Routine Use of [64Cu]Cu-DOTATATE PET/CT in a Neuroendocrine Tumor Center: Referral Patterns and Image Results of 2,249 Consecutive Scans.","authors":"Carlsen, Esben Andreas; Loft, Mathias; Johnbeck, Camilla Bardram; Knigge, Ulrich; Langer, Seppo W; Mortensen, Jann; Enevoldsen, Lotte; Oturai, Peter; Kjaer, Andreas","year":2024,"journal":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 65(11), 1754-1761","doi":"10.2967/jnumed.124.267939","pmid":"39362765","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 2,249 consecutive clinical copper-64 DOTATATE PET/CT scans in 1,290 neuroendocrine tumor patients:\n\n- **Most common indication**: Monitoring without clinical progression (31.3% of scans)\n- **Image results**: No disease in 29.7%, stable disease in 25.9%, progression in 20.5%\n- **PET-only progression**: In 99 of 461 cases with progression (21.5%), disease worsening was detected by PET but not by CT\n- **Initial staging** accounted for 9.8% and **PRRT selection** for 4.2% of scans\n- **16.5% of scans** were for indications not even defined in current appropriate use criteria\n\nThe high detection rate of progression in the monitoring group — particularly PET-only progression — supports upgrading this indication from \"may be appropriate\" to \"appropriate\" in guidelines.","whyItMatters":"Somatostatin receptor PET/CT using peptide-based tracers is the gold standard for imaging neuroendocrine tumors, but guidelines about when to use it are still evolving. This is the largest real-world study of copper-64 DOTATATE, and it provides the evidence base to expand appropriate use criteria. The finding that PET detected progression invisible to CT in over 20% of worsening cases is clinically important — it means some patients would have their disease progression missed without the peptide-based scan.","specificNumbers":"","methodology":"Retrospective analysis of all clinical routine copper-64 DOTATATE PET/CT scans performed at Copenhagen University Hospital-Rigshospitalet from April 2018 to May 2022. Referral text and image reports for all 2,249 scans were reviewed. Each scan's indication was classified according to established appropriate use criteria (AUC). Image results were categorized as no disease, stable, progression, or other.","limitations":"This is a single-center, retrospective study from a specialized neuroendocrine tumor center, which may not reflect practice patterns at general hospitals. Referral bias toward more complex cases could inflate the rate of detected progression. The study did not compare copper-64 DOTATATE directly with gallium-68 DOTATATE or FDG-PET. Clinical outcomes based on scan findings were not reported."},{"rthcId":"RPEP-07934","title":"CGRP monoclonal antibodies and CGRP receptor antagonists (Gepants) in migraine prevention.","authors":"Caronna, Edoardo; Alpuente, Alicia; Torres-Ferrus, Marta; Pozo-Rosich, Patricia","year":2024,"journal":"Handbook of clinical neurology, 199, 107-124","doi":"10.1016/B978-0-12-823357-3.00024-0","pmid":"38307640","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07935","title":"Redefining migraine prevention: early treatment with anti-CGRP monoclonal antibodies enhances response in the real world.","authors":"Caronna, Edoardo; Gallardo, Victor José; Egeo, Gabriella; Vázquez, Manuel Millán; Castellanos, Candela Nieves; Membrilla, Javier A; Vaghi, Gloria; Rodríguez-Montolio, Joana; Fabregat Fabra, Neus; Sánchez-Caballero, Francisco; Jaimes Sánchez, Alex; Muñoz-Vendrell, Albert; Oliveira, Renato; Gárate, Gabriel; González-Osorio, Yésica; Guisado-Alonso, Daniel; Ornello, Raffaele; Thunstedt, Cem; Fernández-Lázaro, Iris; Torres-Ferrús, Marta; Alpuente, Alicia; Torelli, Paola; Aurilia, Cinzia; Pére, Raquel Lamas; Castrillo, Maria José Ruiz; Icco, Roberto De; Sances, Grazia; Broadhurst, Sarah; Ong, Hui Ching; García, Andrea Gómez; Campoy, Sergio; Sanahuja, Jordi; Cabral, Gonçalo; Beltrán Blasco, Isabel; Waliszewska-Prosół, Marta; Pereira, Liliana; Layos-Romero, Almudena; Luzeiro, Isabel; Dorado, Laura; Álvarez Escudero, María Rocio; May, Arne; López-Bravo, Alba; Martins, Isabel Pavão; Sundal, Christina; Irimia, Pablo; Lozano Ros, Alberto; Gago-Veiga, Ana Beatriz; Juanes, Fernando Velasco; Ruscheweyh, Ruth; Sacco, Simona; Cuadrado-Godia, Elisa; García-Azorín, David; Pascual, Julio; Gil-Gouveia, Raquel; Huerta-Villanueva, Mariano; Rodriguez-Vico, Jaime; Viguera Romero, Javier; Obach, Victor; Santos-Lasaosa, Sonia; Ghadiri-Sani, Mona; Tassorelli, Cristina; Díaz-de-Terán, Javier; Díaz Insa, Samuel; Oria, Carmen González; Barbanti, Piero; Pozo-Rosich, Patricia","year":2024,"journal":"Journal of neurology, neurosurgery, and psychiatry, 95(10), 927-937","doi":"10.1136/jnnp-2023-333295","pmid":"38777579","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07936","title":"VACCIMEL, an allogeneic melanoma vaccine, efficiently triggers T cell immune responses against neoantigens and alloantigens, as well as against tumor-associated antigens.","authors":"Carri, Ibel; Schwab, Erika; Trivino, Juan Carlos; von Euw, Erika M; Nielsen, Morten; Mordoh, José; Barrio, María Marcela","year":2024,"journal":"Frontiers in immunology, 15, 1496204","doi":"10.3389/fimmu.2024.1496204","pmid":"39840067","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07937","title":"Effect of CGRP inhibitors on interictal cerebral hemodynamics in individuals with migraine.","authors":"Carter, Sarah C; Cucchiara, Brett; Reehal, Navpreet; Hamilton, Katherine; Kaiser, Eric A; Favilla, Christopher G","year":2024,"journal":"Frontiers in neurology, 15, 1399792","doi":"10.3389/fneur.2024.1399792","pmid":"38746660","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Three months of CGRP monoclonal antibody therapy in migraine patients preserved cerebral autoregulation (CA) and cerebrovascular reactivity (CVR) in both the middle and posterior cerebral arteries (all p>0.38). Blood flow velocity and blood pressure were also unaffected overall. However, patients who responded clinically (>50% migraine reduction) showed a small but significant reduction in cerebral blood flow velocity in MCA (6.0 cm/s, p=0.007) and PCA (8.9 cm/s, p=0.04).","whyItMatters":"CGRP is a potent brain blood vessel dilator, raising concerns that blocking it could impair cerebral blood flow regulation and increase stroke risk. This study provides reassuring evidence that CGRP antibody therapy preserves the brain's critical safety mechanisms (autoregulation and reactivity), while the small blood flow change in responders could serve as a treatment response biomarker.","specificNumbers":"n=23 · 3 months treatment · CA unchanged (MCA p=0.42, PCA p=0.72) · CVR unchanged (MCA p=0.38, PCA p=0.92) · responders: MCA-CBFv -6.0 cm/s (p=0.007), PCA-CBFv -8.9 cm/s (p=0.04)","methodology":"Prospective study of 23 patients with chronic or episodic migraine. Transcranial Doppler ultrasound measured cerebral blood flow velocity in MCA and PCA before and 3 months into CGRP monoclonal antibody therapy. Cerebrovascular reactivity (CVR) and cerebral autoregulation (CA; Mx-index) were calculated. Subgroup analysis compared clinical responders (>50% migraine frequency reduction) to non-responders.","limitations":"Small sample size (n=23). No control group — observed changes could reflect disease natural history. The responder subgroup analysis had even fewer participants, limiting reliability. Only one time point (3 months) assessed. Cannot determine if blood flow velocity changes are clinically meaningful or represent a safety concern. The study assessed interictal (between-migraine) hemodynamics only."},{"rthcId":"RPEP-07938","title":"The real-world safety profile of tirzepatide: pharmacovigilance analysis of the FDA Adverse Event Reporting System (FAERS) database.","authors":"Caruso, I; Di Gioia, L; Di Molfetta, S; Caporusso, M; Cignarelli, A; Sorice, G P; Laviola, L; Giorgino, F","year":2024,"journal":"Journal of endocrinological investigation, 47(11), 2671-2678","doi":"10.1007/s40618-024-02441-z","pmid":"39141075","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07939","title":"Incretin-based therapies for the treatment of obesity-related diseases.","authors":"Caruso, Irene; Cignarelli, Angelo; Sorice, Gian Pio; Perrini, Sebastio; Giorgino, Francesco","year":2024,"journal":"npj metabolic health and disease, 2(1), 31","doi":"10.1038/s44324-024-00030-5","pmid":"40604322","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07940","title":"Photocatalytic Degradation of Bacterial Lipopolysaccharides by Peptide-Coated TiO2 Nanoparticles.","authors":"Caselli, Lucrezia; Du, Guanqun; Micciulla, Samantha; Traini, Tanja; Sebastiani, Federica; Diedrichsen, Ragna Guldsmed; Köhler, Sebastian; Skoda, Maximilian W A; van der Plas, Mariena J A; Malmsten, Martin","year":2024,"journal":"ACS applied materials & interfaces, 16(44), 60056-60069","doi":"10.1021/acsami.4c15706","pmid":"39443826","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07941","title":"Increased Expression of the Neuropeptides PACAP/VIP in the Brain of Mice with CNS Targeted Production of IL-6 Is Mediated in Part by Trans-Signalling.","authors":"Castorina, Alessandro; Scheller, Jurgen; Keay, Kevin A; Marzagalli, Rubina; Rose-John, Stefan; Campbell, Iain L","year":2024,"journal":"International journal of molecular sciences, 25(17)","doi":"10.3390/ijms25179453","pmid":"39273398","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GFAP-IL6 transgenic mice (with astrocyte-targeted IL-6 production) showed significantly increased transcripts and protein levels of both PACAP and VIP, plus their receptors PAC1, VPAC1, and VPAC2, in both cerebrum and cerebellum compared to wild-type littermates. This was accompanied by robust activation of JAK/STAT3, NF-κB, and ERK1/2MAPK signaling pathways. Blocking IL-6 trans-signaling (using sgp130Fc co-expression) reduced VIP expression and attenuated STAT3 and NF-κB activation, but failed to rescue PACAP levels, receptor expression, or ERK1/2MAPK phosphorylation — indicating PACAP induction involves trans-signaling-independent mechanisms.","whyItMatters":"Neuroinflammation is a common feature of Alzheimer's, Parkinson's, multiple sclerosis, and other brain diseases. Understanding that the brain has a built-in neuropeptide defense system that activates in response to inflammation could lead to new therapeutic strategies — potentially boosting PACAP and VIP levels to enhance the brain's natural protective response.","specificNumbers":"","methodology":"Researchers used GFAP-IL6 transgenic mice with CNS-restricted, astrocyte-targeted IL-6 production, compared to wild-type littermates. Bi-genic GFAP-IL6/sgp130Fc mice were used to test whether blocking IL-6 trans-signaling would rescue neuropeptide changes. PACAP and VIP transcript and protein levels were measured in cerebrum and cerebellum, along with receptor expression and activation of JAK/STAT3, NF-κB, and ERK1/2MAPK signaling pathways using RT-qPCR, protein assays, and immunostaining.","limitations":"This was a transgenic mouse study with artificial IL-6 overexpression, which may not fully replicate the nuanced inflammatory processes in human neurodegenerative diseases. The forced IL-6 expression is constitutive and extreme, unlike the fluctuating inflammation seen in clinical conditions. The study did not assess whether the PACAP/VIP upregulation actually conferred neuroprotection in these mice. Behavioral and cognitive outcomes were not measured."},{"rthcId":"RPEP-07942","title":"TLR9 plus STING Agonist Adjuvant Combination Induces Potent Neopeptide T Cell Immunity and Improves Immune Checkpoint Blockade Efficacy in a Tumor Model.","authors":"Castro Eiro, Melisa D; Hioki, Kou; Li, Ling; Wilmsen, Merel E P; Kiernan, Caoimhe H; Brouwers-Haspels, Inge; van Meurs, Marjan; Zhao, Manzhi; de Wit, Harm; Grashof, Dwin G B; van de Werken, Harmen J G; Mueller, Yvonne M; Schliehe, Christopher; Temizoz, Burcu; Kobiyama, Kouji; Ishii, Ken J; Katsikis, Peter D","year":2024,"journal":"Journal of immunology (Baltimore, Md. : 1950), 212(3), 455-465","doi":"10.4049/jimmunol.2300038","pmid":"38063488","tags":["peptide-vaccines"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"A new adjuvant combination — the TLR9 agonist K3 CpG plus the STING agonist c-di-AMP — produced T cell responses against tumor neopeptides that were 10 times stronger than poly-IC (the leading adjuvant currently in clinical neoantigen vaccine trials). When combined with synthetic long peptides (20-mers) from melanoma and lung mesothelioma neoantigens, this formulation induced potent antigen-specific T cell immunity in mice.\n\nIn a melanoma mouse model, the vaccine controlled tumor growth and improved survival, and it synergized with anti-PD-1 checkpoint immunotherapy — meaning the combination worked better than either approach alone.","whyItMatters":"Neoantigen peptide vaccines are a promising strategy for personalized cancer treatment, but their effectiveness depends heavily on the adjuvant that boosts the immune response. Current clinical trial adjuvants produce modest T cell responses. This study identifies a dramatically more potent adjuvant combination (10× improvement) that also synergizes with checkpoint immunotherapy — the backbone of modern cancer treatment. If this translates to humans, it could significantly improve neoantigen vaccine platforms.","specificNumbers":"10× higher T cell responses vs. poly-IC · 20-mer synthetic long peptides · Tested against melanoma and lung mesothelioma neopeptides · Synergy with anti-PD-1 · Tumor growth control and improved survival in B16-F10-OVA mice","methodology":"Researchers tested the K3 CpG (TLR9 agonist) plus c-di-AMP (STING agonist) adjuvant combination with 20-mer synthetic long peptides in mice. They measured dendritic cell activation, antigen-specific T cell responses against multiple neopeptides (from OVA, melanoma, and mesothelioma), tumor growth, and survival. They compared against poly-IC and tested combination with anti-PD-1 checkpoint therapy.","limitations":"This is entirely a mouse study — the adjuvant combination has not been tested in humans. Mouse immune systems differ from human ones, and tumor models in mice don't fully replicate human cancer complexity. The 10× improvement over poly-IC was measured in mice and may not hold in human clinical settings. Safety and tolerability of the dual-adjuvant combination in humans is unknown."},{"rthcId":"RPEP-07943","title":"Multiple metabolic signals in the CeA regulate feeding: The role of AMPK.","authors":"Castro, Gisele; Mendes, Natália Ferreira; Weissmann, Laís; Quaresma, Paula Gabriele Fernandes; Saad, Mario Jose Abdalla; Prada, Patricia Oliveira","year":2024,"journal":"Molecular and cellular endocrinology, 589, 112232","doi":"10.1016/j.mce.2024.112232","pmid":"38604549","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Fasting increased and refeeding decreased AMPK phosphorylation (AMPKThr172) in the central nucleus of the amygdala (CeA), confirming AMPK responds to nutritional status in this brain region.\n\nIntra-CeA ghrelin injection increased both food intake and AMPKThr172 phosphorylation, establishing ghrelin-AMPK signaling as a feeding-promoting pathway in the amygdala. Glucose injection into the CeA decreased feeding, while 2-deoxy-D-glucose (a glucoprivation inducer) increased food intake and blood glucose.\n\nChronic intra-CeA injection of Melanotan II (MTII) over 7 days reduced body mass and food intake with a slight decrease in AMPKThr172, demonstrating that melanocortin peptide signaling opposes the ghrelin-AMPK feeding axis in this brain region.","whyItMatters":"The central amygdala is part of the brain's reward circuitry, which drives cravings for calorie-dense, palatable foods. Understanding how peptide hormones like ghrelin control feeding through AMPK in this region could explain why some people struggle with binge eating and food addiction. The finding that Melanotan II can suppress this circuit over 7 days suggests potential therapeutic targets for appetite control that work through the brain's reward system rather than just the hypothalamus.","specificNumbers":"","methodology":"Eight-week-old male Wistar rats on a chow diet were stereotaxically implanted with cannulas targeting the central amygdala. Researchers injected various modulators directly into the CeA: ghrelin (hunger peptide), glucose, 2-deoxy-D-glucose (glucoprivation agent), and Melanotan II (melanocortin agonist). Food intake was measured after acute injections. For MTII, chronic 7-day injections assessed sustained effects on body weight and food intake. AMPKThr172 phosphorylation was measured via molecular assays. Fasting and refeeding conditions were used to assess baseline AMPK regulation.","limitations":"This is a rat study with direct brain injections, a highly invasive approach that doesn't translate directly to clinical treatment. Exact sample sizes per experimental group were not specified in the abstract. The 2DG-induced feeding increase was accompanied by only faint AMPK increases, suggesting AMPK may not be the only feeding signal in the CeA. The Melanotan II effect on AMPK was described as 'slight,' raising questions about whether AMPK fully mediates the melanocortin feeding suppression in this region."},{"rthcId":"RPEP-07944","title":"Establishment of Baseline Urinary Antimicrobial Peptide Levels by Age: A Prospective Observational Study.","authors":"Caterino, Jeffrey M; Stephens, Julie A; Wexler, Randell; Camargo, Carlos A; Hunold, Katherine M; Wei, Lai; Hains, David; Southerland, Lauren T; Bischof, Jason J; Schwaderer, Andrew","year":2024,"journal":"The journals of gerontology. Series A, Biological sciences and medical sciences, 79(6)","doi":"10.1093/gerona/glad223","pmid":"37708314","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In a study of 308 adults, three of four urinary antimicrobial peptides (HNP 1-3, HD-5, and LL-37) showed no significant differences between adults aged 65+ and those under 65. However, human beta-defensin-2 (hBD-2) was significantly lower in older adults of both sexes (p < .001 for males, p = .004 for females). Additionally, urine leukocyte esterase was associated with increased HNP 1-3 and HD-5 levels, hematuria with increased hBD-2, and contaminated urine cultures with increased HNP 1-3 and hBD-2.","whyItMatters":"Older adults are much more susceptible to urinary tract infections, and understanding whether their innate immune defense peptides in urine change with age could explain this vulnerability. The finding that hBD-2 specifically declines with age while other antimicrobial peptides remain stable suggests a targeted gap in urinary tract defense that could be investigated as both a diagnostic marker and a potential therapeutic target.","specificNumbers":"","methodology":"Cross-sectional study of 308 patients aged 18 and older at a family medicine clinic during nonacute visits. Urine samples were analyzed using enzyme-linked immunosorbent assays (ELISA) for four antimicrobial peptides: HNP 1-3, HD-5, hBD-2, and LL-37. Associations between age and AMP levels were tested using both unadjusted and multivariable linear regression models.","limitations":"The cross-sectional design captures a single time point and cannot track changes in individual patients over time. The study was conducted at a single family medicine clinic, which may limit generalizability. The sample size of 308, while reasonable, may not capture the full range of variability across different age groups, ethnicities, or health conditions."},{"rthcId":"RPEP-07945","title":"PIONEER REAL Sweden: A Multicentre, Prospective, Real-World Observational Study of Oral Semaglutide Use in Adults with Type 2 Diabetes in Swedish Clinical Practice.","authors":"Catrina, Sergiu-Bogdan; Amadid, Hanan; Braae, Uffe C; Dereke, Jonatan; Ekberg, Neda Rajamand; Klanger, Boris; Jansson, Stefan","year":2024,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 15(9), 2079-2095","doi":"10.1007/s13300-024-01614-6","pmid":"39052163","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07946","title":"Gene therapy for epilepsy targeting neuropeptide Y and its Y2 receptor to dentate gyrus granule cells.","authors":"Cattaneo, Stefano; Bettegazzi, Barbara; Crippa, Lucia; Asth, Laila; Regoni, Maria; Soukupova, Marie; Zucchini, Silvia; Cantore, Alessio; Codazzi, Franca; Valtorta, Flavia; Simonato, Michele","year":2024,"journal":"EMBO reports, 25(10), 4387-4409","doi":"10.1038/s44319-024-00244-0","pmid":"39251828","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07947","title":"Modern Challenges in Type 2 Diabetes: Balancing New Medications with Multifactorial Care.","authors":"Caturano, Alfredo; Galiero, Raffaele; Rocco, Maria; Tagliaferri, Giuseppina; Piacevole, Alessia; Nilo, Davide; Di Lorenzo, Giovanni; Sardu, Celestino; Vetrano, Erica; Monda, Marcellino; Marfella, Raffaele; Rinaldi, Luca; Sasso, Ferdinando Carlo","year":2024,"journal":"Biomedicines, 12(9)","doi":"10.3390/biomedicines12092039","pmid":"39335551","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07948","title":"Molecular determinants for brain targeting by peptides: a meta-analysis approach with experimental validation.","authors":"Cavaco, Marco; Fraga, Patrícia; Valle, Javier; Silva, Ruben D M; Gano, Lurdes; Correia, João D G; Andreu, David; Castanho, Miguel A R B; Neves, Vera","year":2024,"journal":"Fluids and barriers of the CNS, 21(1), 45","doi":"10.1186/s12987-024-00545-5","pmid":"38802930","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07949","title":"Can glucagon-like peptide-1 receptor agonists induce asthma? An analysis of the FAERS database.","authors":"Cazzola, Mario; Matera, Maria Gabriella; Calzetta, Luigino; Lauro, Davide; Rogliani, Paola","year":2024,"journal":"The Journal of asthma : official journal of the Association for the Care of Asthma, 61(12), 1638-1645","doi":"10.1080/02770903.2024.2372600","pmid":"38913778","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07950","title":"Roles of NET Peptides With Known Antimicrobial Activity and Toxicity in Immune Response.","authors":"Cebeci, Sinan; Polat, Tuba; Ünübol, Nihan","year":2024,"journal":"Journal of immunology research, 2024, 5528446","doi":"10.1155/jimr/5528446","pmid":"39759156","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07951","title":"Case report: Resolution of VIPoma-related symptoms with peptide receptor radionuclide therapy.","authors":"Cengiz, Turgut Bora; Kulkarni, Raksha; Corbett, Virginia; Ghesani, Nasrin V; Wolin, Edward; Ghesani, Munir V","year":2024,"journal":"Frontiers in oncology, 14, 1432758","doi":"10.3389/fonc.2024.1432758","pmid":"39845312","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07952","title":"Exenatide administration time determines the effects on blood pressure dipping in db/db mice via modulation of food intake and sympathetic activity.","authors":"Chacon, Aaron N; Su, Wen; Hou, Tianfei; Guo, Zhenheng; Gong, Ming C","year":2024,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2024.07.02.601700","pmid":"39005289","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07953","title":"LC-HRMS and NMR studies for the characterization of degradation impurities of ubrogepant along with the in silico approaches for the prediction of degradation and toxicity.","authors":"Chaganti, Sowmya; Chauhan, Usha; Bhatt, Nehal; Kommalapati, Hemasree; Golla, Vijaya Madhyanapu; Pilli, Pushpa; Samanthula, Gananadhamu","year":2024,"journal":"Journal of pharmaceutical and biomedical analysis, 243, 116117","doi":"10.1016/j.jpba.2024.116117","pmid":"38522383","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07954","title":"Liraglutide for the Treatment of Severe Hypoglycemia Following Total Pancreatectomy and Islet Autotransplantation.","authors":"Chan, Christopher; Hawthorne, Wayne; Pleass, Henry; Holmes-Walker, Deborah Jane","year":2024,"journal":"JCEM case reports, 2(11), luae178","doi":"10.1210/jcemcr/luae178","pmid":"39450137","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07955","title":"Exendin-4, a glucagon-like peptide-1 receptor agonist, alleviates muscular dysfunction and wasting in a streptozotocin-induced diabetic mouse model compared to metformin.","authors":"Chan, Ding-Cheng; Lin, Yuan-Cheng; Tzeng, Huei-Ping; Yang, Rong-Sen; Chiang, Meng-Tsan; Liu, Shing-Hwa","year":2024,"journal":"Tissue & cell, 89, 102479","doi":"10.1016/j.tice.2024.102479","pmid":"39018713","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07956","title":"Liraglutide alleviates experimental diabetic cardiomyopathy in a PDH-dependent manner.","authors":"Chan, Jordan S F; Greenwell, Amanda A; Saed, Christina T; Stenlund, Magnus J; Mangra-Bala, Indiresh A; Tabatabaei Dakhili, Seyed Amirhossein; Yang, Kunyan; Ferrari, Sally R; Eaton, Farah; Gopal, Keshav; Ussher, John R","year":2024,"journal":"The Journal of endocrinology, 262(2)","doi":"10.1530/JOE-24-0032","pmid":"38860519","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07957","title":"Design-rules for stapled peptides with in vivo activity and their application to Mdm2/X antagonists.","authors":"Chandramohan, Arun; Josien, Hubert; Yuen, Tsz Ying; Duggal, Ruchia; Spiegelberg, Diana; Yan, Lin; Juang, Yu-Chi Angela; Ge, Lan; Aronica, Pietro G; Kaan, Hung Yi Kristal; Lim, Yee Hwee; Peier, Andrea; Sherborne, Brad; Hochman, Jerome; Lin, Songnian; Biswas, Kaustav; Nestor, Marika; Verma, Chandra S; Lane, David P; Sawyer, Tomi K; Garbaccio, Robert; Henry, Brian; Kannan, Srinivasaraghavan; Brown, Christopher J; Johannes, Charles W; Partridge, Anthony W","year":2024,"journal":"Nature communications, 15(1), 489","doi":"10.1038/s41467-023-43346-4","pmid":"38216578","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07958","title":"A Scoping Review of GLP-1 Receptor Agonists: Are They Associated with Increased Gastric Contents, Regurgitation, and Aspiration Events?","authors":"Chang, Marvin G; Ripoll, Juan G; Lopez, Ernesto; Krishnan, Kumar; Bittner, Edward A","year":2024,"journal":"Journal of clinical medicine, 13(21)","doi":"10.3390/jcm13216336","pmid":"39518474","tags":[],"studyType":"Scoping Review","evidenceStrength":"moderate","keyFinding":"While GLP-1 receptor agonists do increase residual gastric contents (19-56% of users vs. 5-20% of non-users in 7 of 8 comparative studies), the available evidence does not show a significant increase in actual aspiration or regurgitation events. In three retrospective studies that specifically tracked aspiration events, one found nearly identical rates (4.8 vs. 4.6 per 10,000) and the other two found only one aspiration event in GLP-1 users versus none in controls.\n\nCritically, the review found that nearly all studies had significant confounding factors — patients on GLP-1 drugs typically had diabetes, obesity, and other conditions that independently delay gastric emptying. The authors conclude that current societal guidelines recommending withholding GLP-1 drugs before surgery may not be well-supported by the available data.","whyItMatters":"Millions of people on GLP-1 drugs face surgery every year, and many medical societies have issued guidance to stop these medications days or weeks before procedures due to aspiration fears. This review challenges that approach by showing that while GLP-1 drugs do slow stomach emptying (as expected from their mechanism), the feared increase in aspiration events hasn't materialized in the data. This has direct implications for perioperative guidelines and patient safety protocols.","specificNumbers":"3,712 citations screened · 24 studies included · 19-56% residual gastric contents in GLP-1 users vs. 5-20% in non-users · Aspiration rate: 4.8 vs. 4.6 per 10,000 · 6 GLP-1 drugs studied · All but 1 study had confounding factors","methodology":"Librarian-assisted scoping review searching five electronic databases (PubMed, Embase, Web of Science, KCI, MEDLINE, Preprint Citation Index) from inception through March 2024. Included 24 studies (4 prospective, 6 retrospective, 5 case series, 9 case reports) evaluating residual gastric volume, retained food contents, regurgitation, and aspiration events in GLP-1 RA users. Two independent reviewers screened articles with systematic data extraction.","limitations":"Most included studies had significant confounding factors (diabetes, other medications, comorbidities) that independently affect gastric emptying, making it difficult to isolate the GLP-1 effect. The evidence base is mostly observational with no RCTs. Case reports and case series (14 of 24 studies) provide low-quality evidence. The review covers studies through March 2024, so very recent data may not be included."},{"rthcId":"RPEP-07959","title":"The sensitive detection of low molecular mass peptide drugs in dried blood spots by solid-phase extraction and LC-HRMS.","authors":"Chang, Wei; Yan, Siyu; Yan, Xiya; Wang, Zhanliang; Gu, Boya; Liu, Yunxi; Zhang, Yufeng; Yang, Sheng","year":2024,"journal":"Analytical and bioanalytical chemistry, 416(26), 5655-5669","doi":"10.1007/s00216-024-05480-w","pmid":"39180594","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07960","title":"Correlation Study of Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs) on Diabetic Patients with Hypertension.","authors":"Chang, Yeting; Yu, Qin","year":2024,"journal":"Iranian journal of public health, 53(7), 1560-1568","doi":"10.18502/ijph.v53i7.16050","pmid":"39086405","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07961","title":"Effects of glucagon-like peptide-1 receptor agonists on gastric mucosal visibility and retained gastric contents during EGD.","authors":"Chapman, Malcolm B; Norwood, Dalton A; Price, Christopher; Abdulhadi, Basma; Kyanam Kabir Baig, Kondal; Ahmed, Ali M; Peter, Shajan; Routman, Justin S; Sánchez-Luna, Sergio A; Duggan, Elizabeth W; Mulki, Ramzi","year":2024,"journal":"Gastrointestinal endoscopy, 100(5), 923-927","doi":"10.1016/j.gie.2024.05.012","pmid":"38759761","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07962","title":"Automated Flow Peptide Synthesis Enables Engineering of Proteins with Stabilized Transient Binding Pockets.","authors":"Charalampidou, Anna; Nehls, Thomas; Meyners, Christian; Gandhesiri, Satish; Pomplun, Sebastian; Pentelute, Bradley L; Lermyte, Frederik; Hausch, Felix","year":2024,"journal":"ACS central science, 10(3), 649-657","doi":"10.1021/acscentsci.3c01283","pmid":"38559286","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07963","title":"Characteristics associated with response to subcutaneously administered anti-CGRP monoclonal antibody medications in a real-world community cohort of persons living with migraine: A retrospective clinical and genetic study.","authors":"Chase, Bruce A; Semenov, Irene; Rubin, Susan; Meyers, Steven; Mark, Angela; Makhlouf, Thomas; Chirayil, Tanya T; Maraganore, Demetrius; Wei, Jun; Zheng, Siqun L; Xu, Jianfeng; Epshteyn, Alexander; Pham, Anna; Frigerio, Roberta; Markopoulou, Katerina","year":2024,"journal":"Headache, 64(1), 68-92","doi":"10.1111/head.14655","pmid":"38071464","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07964","title":"Shared Genetics of Migraine and Gastrointestinal Disorders Implicates Underlying Neurologic Mechanisms Yet Heterogeneous Etiologies.","authors":"Chasman, Daniel I; Guo, Yanjun; Chan, Andrew T; Rist, Pamela M; Staller, Kyle","year":2024,"journal":"Neurology. Genetics, 10(6), e200201","doi":"10.1212/NXG.0000000000200201","pmid":"39677849","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Migraine showed strong genetic correlation with non-immune GI disorders: IBS (rg = 0.37, p = 10⁻²¹), GERD, PUD, FD, and DD. No correlation was found with IBD. However, local genetic sharing at the CALCA/CALCB genes (encoding CGRP) was concordant and significant for diverticular disease, IBD, and ulcerative colitis, suggesting anti-CGRP therapies could benefit these conditions.\n\nMendelian randomization supported causal effects of some GI conditions on migraine — particularly diverticular disease (OR 1.90, p = 2.2 × 10⁻⁴) — but not of migraine on GI conditions. CNS-related genes were enriched in the genetic overlap of GERD, IBS, and PUD with migraine, supporting neurologic mechanisms.","whyItMatters":"If CGRP plays a shared role in both migraine and certain GI disorders, then anti-CGRP drugs — which have proven transformative for migraine — could potentially be repurposed for diverticular disease and inflammatory bowel disease. This genetic evidence provides the rationale for clinical trials exploring these new applications of CGRP-targeting peptide therapies.","specificNumbers":"","methodology":"Genome-wide genetic correlation analysis using summary statistics from large-scale GWAS studies for migraine (including by aura status), IBS, PUD, GERD, FD, DD, IBD, UC, and CD. Local genetic correlation was assessed at independent genome regions. Enrichment analysis examined tissue specificity of shared genes. Mendelian randomization assessed potential causal relationships. Specific attention was paid to CALCA/CALCB (CGRP) and serotonin-related loci.","limitations":"Genetic correlation does not prove shared mechanisms — the same genes could act through different pathways in different tissues. The Mendelian randomization results suggest GI conditions cause migraine but not vice versa, which is counterintuitive and may reflect methodological limitations. GWAS data is primarily from European populations. The study does not prove anti-CGRP drugs would work for GI conditions — clinical trials are needed."},{"rthcId":"RPEP-07965","title":"Diabetes insipidus: Vasopressin deficiency….","authors":"Chasseloup, Fanny; Tabarin, Antoine; Chanson, Philippe","year":2024,"journal":"Annales d'endocrinologie, 85(4), 294-299","doi":"10.1016/j.ando.2023.11.006","pmid":"38316255","tags":["vasopressin","desmopressin"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"This review summarizes the current understanding of diabetes insipidus — now proposed to be renamed 'vasopressin deficiency' (central form) and 'vasopressin resistance' (nephrogenic form) to avoid confusion with diabetes mellitus. The standard treatment for central diabetes insipidus is desmopressin, a synthetic analog of the peptide hormone vasopressin.\n\nImportantly, the review highlights that desmopressin treatment doesn't always restore optimal quality of life. The authors suggest this may be because patients with neurohypophyseal dysfunction are also deficient in oxytocin, another peptide hormone secreted from the same brain region. A new diagnostic test using oxytocin stimulation could help identify these patients.","whyItMatters":"Diabetes insipidus affects the body's ability to regulate water balance, leading to excessive urination and thirst. While desmopressin effectively manages the vasopressin deficiency, the observation that patients still report reduced quality of life opens the door to understanding oxytocin's overlooked role — potentially leading to combination peptide therapies that address both deficiencies.","specificNumbers":"2 proposed name changes · central (vasopressin deficiency) and nephrogenic (vasopressin resistance) forms · desmopressin as standard treatment · copeptin stimulation test for diagnosis","methodology":"This is a narrative review article summarizing the classification, diagnosis, and treatment of diabetes insipidus. It covers diagnostic approaches including water deprivation tests and copeptin stimulation with hypertonic saline, and discusses the emerging concept of concurrent oxytocin deficiency.","limitations":"As a review article, this does not present new experimental data. The hypothesis that oxytocin deficiency contributes to reduced quality of life in diabetes insipidus patients has not been fully established. The proposed oxytocin stimulation test is still investigational."},{"rthcId":"RPEP-07966","title":"Immunomodulatory peptides: new therapeutic horizons for emerging and re-emerging infectious diseases.","authors":"Chatterjee, Debolina; Sivashanmugam, Karthikeyan","year":2024,"journal":"Frontiers in microbiology, 15, 1505571","doi":"10.3389/fmicb.2024.1505571","pmid":"39760081","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07967","title":"Peptidomics-based study of antihypertensive activity: discovery of novel ACE inhibiting peptides from peanut yogurt.","authors":"Chen, Baiyan; Wang, Xiaoying; Zhang, Jiuyan; Wang, Li","year":2024,"journal":"Food & function, 15(12), 6705-6716","doi":"10.1039/d4fo00299g","pmid":"38832529","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07968","title":"Exenatide for obesity in children and adolescents: Systematic review and meta-analysis.","authors":"Chen, Bin; Zou, Zhuan; Zhang, Xiaoyan; Xiao, Dongqiong; Li, Xihong","year":2024,"journal":"Frontiers in pharmacology, 15, 1290184","doi":"10.3389/fphar.2024.1290184","pmid":"38633611","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07969","title":"Role of thymosin α1 in restoring immune response in immunological nonresponders living with HIV.","authors":"Chen, Chaoyu; Wang, Jiangrong; Xun, Jingna; Zhang, Xinyu; Liu, Li; Song, Zichen; Zhang, Renfang; Chen, Jun; Lu, Hongzhou","year":2024,"journal":"BMC infectious diseases, 24(1), 97","doi":"10.1186/s12879-024-08985-y","pmid":"38233816","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07970","title":"Hydrolyzed egg yolk peptide prevented osteoporosis by regulating Wnt/β-catenin signaling pathway in ovariectomized rats.","authors":"Chen, Chuanjing; Huang, Ludi; Chen, Yuanyuan; Jin, Jin; Xu, Ze; Liu, Fei; Li, Kelei; Sun, Yongye","year":2024,"journal":"Scientific reports, 14(1), 10227","doi":"10.1038/s41598-024-60514-8","pmid":"38702443","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Micro-CT analysis showed that both low-dose (10 mg/kg/day) and high-dose (40 mg/kg/day) hydrolyzed egg yolk peptide (YPEP) improved bone mineral density and bone microstructure in ovariectomized rats. Three-point bending tests confirmed enhanced biomechanical strength.\n\nSerum markers of bone formation (BALP, BGP, calcium, phosphorus) were significantly elevated in YPEP groups, while bone resorption markers (ALP, TRAP, CTX-I) were reduced in the low-dose group. At the molecular level, YPEP upregulated key proteins in the Wnt/β-catenin pathway (Wnt3a, β-catenin, LRP5, RUNX2, OPG) and increased the OPG/RANKL ratio — shifting the balance from bone breakdown toward bone formation. Gut microbiota changes (increased Lachnospiraceae_NK4A136_group, decreased Escherichia_Shigella) were observed but did not correlate with bone outcomes.","whyItMatters":"Finding natural, food-derived peptides that can prevent bone loss is significant because current osteoporosis treatments (like bisphosphonates and estrogen) carry side effects that limit long-term use. Egg yolk peptides are readily available and potentially safer for chronic use. Identifying the Wnt/β-catenin pathway as the mechanism provides a clear target for further research and could lead to novel nutraceutical approaches to osteoporosis prevention.","specificNumbers":"","methodology":"Sprague-Dawley rats were divided into five groups: sham surgery, ovariectomy (OVX), estradiol treatment (25 µg/kg/day as positive control), low-dose YPEP (10 mg/kg/day), and high-dose YPEP (40 mg/kg/day). Femur bones were analyzed by micro-CT for density and structure, three-point bending for mechanical strength, and serum markers for bone turnover. Wnt/β-catenin pathway proteins were measured, and gut microbiota composition was assessed at the genus level with correlation analysis.","limitations":"This was an animal study in rats, and results may not translate directly to humans. The exact peptide sequences in the hydrolyzed egg yolk preparation were not characterized, making it difficult to identify the active component(s). The gut microbiota changes did not correlate with bone outcomes, weakening the gut-bone axis hypothesis for this particular treatment. Sample sizes per group were not specified in the abstract. The study duration was not stated."},{"rthcId":"RPEP-07971","title":"Myocardial contrast echocardiography evaluation of coronary microvascular dysfunction to Predict MACEs in patients with heart failure with preserved ejection fraction follow-up.","authors":"Chen, Fuhua; Weng, Wenchao; Yang, Daoling; Wang, Xiaomin; Zhou, Yibo","year":2024,"journal":"BMC cardiovascular disorders, 24(1), 496","doi":"10.1186/s12872-024-04173-7","pmid":"39289634","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07972","title":"Exploration of Bioactive Umami Peptides from Wheat Gluten: Umami Mechanism, Antioxidant Activity, and Potential Disease Target Sites.","authors":"Chen, Haowen; Zhao, Huiyan; Li, Cuiling; Zhou, Chunxia; Chen, Jianxu; Xu, Wenjie; Jiang, Guili; Guan, Jingjing; Du, Zhuorong; Luo, Donghui","year":2024,"journal":"Foods (Basel, Switzerland), 13(23)","doi":"10.3390/foods13233805","pmid":"39682877","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07973","title":"Hit-and-run vaccine system that overcomes limited neoantigen epitopes for efficient broad antitumor response.","authors":"Chen, Hongyu; Huang, Zichao; Li, Jiaxuan; Dong, Si; Xu, Yudi; Ma, Sheng; Zhao, Jiayu; Liu, Liping; Sun, Tianmeng; Song, Wantong; Chen, Xuesi","year":2024,"journal":"Science bulletin, 69(7), 922-932","doi":"10.1016/j.scib.2024.01.039","pmid":"38331707","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07974","title":"Uniform Polymeric Nanovaccine Platform for Improving the Availability and Efficacy of Neoantigen Peptides.","authors":"Chen, Hongyu; Zhu, Zhenyi; Lv, Kuncheng; Qi, Yibo; Si, Xinghui; Ma, Sheng; Song, Wantong; Chen, Xuesi","year":2024,"journal":"Nano letters, 24(33), 10114-10123","doi":"10.1021/acs.nanolett.4c02196","pmid":"39109634","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The poly(2-oxazoline)-based nanovaccine platform self-assembled into uniform ~50 nm nanoparticles and could conjugate neoantigen peptides regardless of their physicochemical properties. This improved antigen accumulation and infiltration in lymph nodes, enhancing antigen presentation to immune cells.\n\nWhen conjugated with three predicted neoantigen peptides from the MC38 colon tumor cell line, the nanovaccine induced robust CD8+ T cell responses in 100% of vaccinated mice and achieved superior tumor clearance compared to free (unconjugated) peptides.","whyItMatters":"A major bottleneck in personalized cancer vaccines is that each patient's tumor has unique neoantigens with different chemical properties, making standardized manufacturing difficult. This platform solves that by working with any peptide, potentially enabling scalable production of truly personalized cancer treatments.","specificNumbers":"","methodology":"Researchers synthesized a polymer carrier based on poly(2-oxazoline)s and chemically conjugated neoantigen peptides to it. The resulting nanoparticles were characterized for size and uniformity. In vivo experiments in mice bearing MC38 colon tumors compared tumor growth and CD8+ T cell responses between nanovaccine-treated and free-peptide-treated groups.","limitations":"This was a preclinical study in mice using a single tumor model (MC38). Results in mouse models often don't translate directly to humans. Only three neoantigen peptides were tested, and long-term durability of the immune response was not assessed. Manufacturing scalability and safety in humans remain to be established."},{"rthcId":"RPEP-07975","title":"Biomimetic nanocarriers loaded with temozolomide by cloaking brain-targeting peptides for targeting drug delivery system to promote anticancer effects in glioblastoma cells.","authors":"Chen, Huaming; Wang, Yunhong; Wang, Hai; Zhang, Kun; Liu, Yunfei; Li, Qiangfeng; Li, Chengli; Wen, Zhonghui; Chen, Ziyu","year":2024,"journal":"Heliyon, 10(7), e28256","doi":"10.1016/j.heliyon.2024.e28256","pmid":"38596030","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07976","title":"A quick and innovative pipeline for producing chondrocyte-homing peptide-modified extracellular vesicles by three-dimensional dynamic culture of hADSCs spheroids to modulate the fate of remaining ear chondrocytes in the M1 macrophage-infiltrated microenvironment.","authors":"Chen, Jianguo; Zhang, Enchong; Wan, Yingying; Huang, Tianyu; Wang, Yuchen; Jiang, Haiyue","year":2024,"journal":"Journal of nanobiotechnology, 22(1), 300","doi":"10.1186/s12951-024-02567-5","pmid":"38816719","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07977","title":"Development of [177Lu]Lu-LNC1010 for peptide receptor radionuclide therapy of nasopharyngeal carcinoma.","authors":"Chen, Jianhao; Pang, Yizhen; Liao, Xiyi; Zhou, Yangfan; Luo, Qicong; Wu, Hua; Zuo, Changjing; Zhang, Jingjing; Lin, Qin; Chen, Xiaoyuan; Zhao, Liang; Chen, Haojun","year":2024,"journal":"European journal of nuclear medicine and molecular imaging, 52(1), 247-259","doi":"10.1007/s00259-024-06874-9","pmid":"39145784","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A new somatostatin receptor-targeting radioactive peptide, [177Lu]Lu-LNC1010, showed higher tumor uptake, longer retention, and greater tumor growth inhibition than the standard [177Lu]Lu-DOTATATE in nasopharyngeal carcinoma (NPC) cell and mouse models. The enhanced performance comes from an Evans blue-binding moiety and PEG linker added to the DOTATATE backbone, which extends circulation time. In a proof-of-concept human case, PRRT with LNC1010 achieved favorable therapeutic results with negligible side effects in a metastatic NPC patient.","whyItMatters":"Peptide receptor radionuclide therapy (PRRT) has been revolutionary for neuroendocrine tumors but hasn't been applied to other cancers. This study shows SSTR2 is expressed on nasopharyngeal carcinoma and that a modified somatostatin peptide can deliver radioactivity directly to these tumors. If validated, this could extend PRRT — one of the most successful peptide-based cancer treatments — to a completely new cancer type.","specificNumbers":"Higher tumor uptake and longer retention than DOTATATE in xenografts; greater tumor growth inhibition; 1 pilot clinical patient treated with favorable response","methodology":"Multi-phase study: in vitro binding assays on C666-1 NPC cells, PET/SPECT imaging and biodistribution studies in C666-1 xenograft mouse models comparing LNC1010 vs DOTATATE, preclinical PRRT efficacy studies in mice, and a single-patient proof-of-concept clinical pilot.","limitations":"Preclinical data comes from a single NPC cell line (C666-1). The human clinical evidence consists of only one patient — far too small for clinical conclusions. Long-term safety and efficacy data are lacking. Kidney retention of radioactive peptides is a known concern not fully addressed."},{"rthcId":"RPEP-07978","title":"Two novel angiotensin-converting enzyme (ACE) and dipeptidyl peptidase IV (DPP-IV) inhibiting peptides from tilapia (Oreochromis mossambicus) skin and their molecular docking mechanism.","authors":"Chen, Jiayi; Ji, Hongwu; Luo, Jing; Zhang, Di; Liu, Shucheng","year":2024,"journal":"Journal of food science, 89(6), 3603-3617","doi":"10.1111/1750-3841.17059","pmid":"38638071","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07979","title":"Glucagon-like peptide-1 receptor agonist exendin 4 ameliorates diabetes-associated vascular calcification by regulating mitophagy through the AMPK signaling pathway.","authors":"Chen, Kui; Jin, Hao-Jie; Wu, Zi-Heng; Zhang, Bao-Fu; Wu, Jun; Huang, Zi-Yi; Huang, Ying-Peng; Lu, Xin-Wu; Zheng, Xiang-Tao","year":2024,"journal":"Molecular medicine (Cambridge, Mass.), 30(1), 58","doi":"10.1186/s10020-024-00817-8","pmid":"38720283","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07980","title":"Effects of 3-month liraglutide treatment on oxidative stress and inflammation in type 2 diabetes patients with different urinary albumin-to-creatinine ratio categories.","authors":"Chen, Shumei; He, Meiqing; Qin, Yufan; Tian, Jing; Liang, Zerong; Li, Ying; Wang, Peihua; Zhang, Youzhi; Zhou, Cui; Xiao, Juan","year":2024,"journal":"Medicine, 103(47), e40438","doi":"10.1097/MD.0000000000040438","pmid":"39809212","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Three months of liraglutide treatment significantly reduced albuminuria in type 2 diabetes patients with both microalbuminuria and macroalbuminuria, with greater reductions in patients who had worse kidney function at baseline. Liraglutide also decreased inflammatory markers (TNF-α, IL-6, MCP-1) and oxidative stress markers (MDA) while increasing antioxidant enzymes (SOD, glutathione peroxidase) across all patient groups. The degree of albuminuria reduction correlated with improvements in oxidative stress and inflammation, suggesting these mechanisms underlie liraglutide's kidney-protective effects. Blood sugar, HbA1c, and BMI also improved in all groups.","whyItMatters":"Diabetic kidney disease is the leading cause of kidney failure globally. This study provides clinical evidence that liraglutide's kidney-protective effects are linked to reducing oxidative stress and inflammation — not just improving blood sugar. Importantly, patients with the worst kidney damage (highest albuminuria) benefited the most, suggesting this GLP-1 peptide drug could be particularly valuable for patients already developing kidney complications.","specificNumbers":"n=107 · 3 UACR groups · fasting glucose, HbA1c, BMI all decreased (p<0.05) · UACR decreased in groups II (p=0.005) and III (p=0.001) · TNF-α, IL-6, MCP-1, MDA decreased · SOD and GPx increased (all p<0.05)","methodology":"This prospective study enrolled 107 type 2 diabetes patients initiating liraglutide, categorized into three groups by baseline urinary albumin-to-creatinine ratio (UACR): normal (<30 mg/g), microalbuminuria (30-300 mg/g), and macroalbuminuria (>300 mg/g). Before and after 3 months of treatment, researchers measured metabolic parameters, kidney function markers, and oxidative stress/inflammation biomarkers including TNF-α, IL-6, MCP-1, MDA, SOD, and glutathione peroxidase.","limitations":"This is a single-arm study with no control group, so improvements could partly reflect concurrent lifestyle changes or natural regression to the mean. The 3-month follow-up is relatively short for assessing kidney outcomes. The sample size of 107 patients is moderate, with smaller numbers in each UACR subgroup. The study did not account for other kidney-protective medications patients may have been taking."},{"rthcId":"RPEP-07981","title":"Assessment of Changes in Body Composition After 3 Months of Dulaglutide Treatment.","authors":"Chen, Shuqin; Wang, Xuepeng; Jin, Yong; Chen, Xueqin; Song, Qifa; Wei, Gang; Li, Li","year":2024,"journal":"Diabetes, metabolic syndrome and obesity : targets and therapy, 17, 1301-1308","doi":"10.2147/DMSO.S443631","pmid":"38505539","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07982","title":"Neuroimmunological effects of omega-3 fatty acids on migraine: a review.","authors":"Chen, Ting-Bin; Yang, Cheng-Chia; Tsai, I-Ju; Yang, Hao-Wen; Hsu, Yung-Chu; Chang, Ching-Mao; Yang, Chun-Pai","year":2024,"journal":"Frontiers in neurology, 15, 1366372","doi":"10.3389/fneur.2024.1366372","pmid":"38770523","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07983","title":"Psychiatric adverse events associated with GLP-1 receptor agonists: a real-world pharmacovigilance study based on the FDA Adverse Event Reporting System database.","authors":"Chen, Wei; Cai, Peishan; Zou, Wenbin; Fu, Zhiwen","year":2024,"journal":"Frontiers in endocrinology, 15, 1330936","doi":"10.3389/fendo.2024.1330936","pmid":"38390214","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07984","title":"Engineering Supramolecular Nanofiber Depots from a Glucagon-Like Peptide-1 Therapeutic.","authors":"Chen, Weike; Xian, Sijie; Webber, Bernice; DeWolf, Emily L; Schmidt, Connor R; Kilmer, Rory; Liu, Dongping; Power, Elizabeth M; Webber, Matthew J","year":2024,"journal":"ACS nano, 18(45), 31274-31285","doi":"10.1021/acsnano.4c10248","pmid":"39471057","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07985","title":"Clinical effect of recombinant human brain natriuretic peptide in the treatment of heart failure in elderly patients.","authors":"Chen, Wenjuan","year":2024,"journal":"BMC cardiovascular disorders, 24(1), 517","doi":"10.1186/s12872-024-04190-6","pmid":"39333886","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07986","title":"GLP-1R-positive neurons in the lateral septum mediate the anorectic and weight-lowering effects of liraglutide in mice.","authors":"Chen, Zijun; Deng, Xiaofei; Shi, Cuijie; Jing, Haiyang; Tian, Yu; Zhong, Jiafeng; Chen, Gaowei; Xu, Yunlong; Luo, Yixiao; Zhu, Yingjie","year":2024,"journal":"The Journal of clinical investigation, 134(17)","doi":"10.1172/JCI178239","pmid":"39225090","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 receptor-positive neurons in the lateral septum (LSGLP-1R) were robustly activated by liraglutide. Chemogenetic activation of these neurons dramatically suppressed feeding. Critically, targeted knockdown of GLP-1 receptors in the lateral septum — but not in the hypothalamus — substantially attenuated liraglutide's ability to inhibit feeding and lower body weight. The activity of LSGLP-1R neurons rapidly decreased during naturalistic feeding episodes, and synaptic inactivation of these neurons diminished liraglutide's anorexic effects.","whyItMatters":"This study fundamentally shifts understanding of where GLP-1 drugs work in the brain. The hypothalamus has long been considered the primary appetite center, but this research shows the lateral septum is actually the critical site for liraglutide's effects. This has major implications for developing next-generation GLP-1 peptide drugs that could be designed to target the lateral septum more specifically, potentially improving efficacy or reducing side effects.","specificNumbers":"","methodology":"Mouse study using multiple neuroscience techniques: chemogenetics (DREADDs) to artificially activate or silence specific neurons, targeted gene knockdown to remove GLP-1 receptors from specific brain regions, calcium imaging to record neuron activity during feeding, and synaptic inactivation to test whether neuronal connections are required for liraglutide's effects.","limitations":"This is a mouse study, and the relative importance of the lateral septum versus other brain regions may differ in humans. The techniques used (chemogenetics, targeted knockdown) are powerful but not perfectly specific. Liraglutide was the only GLP-1 agonist tested, and other drugs in the class (semaglutide, tirzepatide) may have different brain region dependencies. Long-term metabolic effects beyond acute feeding suppression were not extensively characterized."},{"rthcId":"RPEP-07987","title":"Role of LRP5/6/GSK-3β/β-catenin in the differences in exenatide- and insulin-promoted T2D osteogenesis and osteomodulation.","authors":"Chen, Zijun; Wang, Yuxi; Zhang, Guanhua; Zheng, Jian; Tian, Lei; Song, Yingliang; Liu, Xiangdong","year":2024,"journal":"British journal of pharmacology, 181(19), 3556-3575","doi":"10.1111/bph.16421","pmid":"38804080","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The GLP-1 receptor agonist exenatide significantly outperformed insulin in promoting bone formation and implant integration in diabetic rats. Exenatide extensively promoted peri-implant osseointegration through the LRP5/6/GSK-3β/β-catenin Wnt signaling pathway, while also inhibiting fat formation (via BMPR1A suppression) and reducing inflammation (via β-TrCP). Both in vivo micro-CT analysis and in vitro bone marrow stromal cell experiments confirmed exenatide's superior osteogenic effects compared to insulin.","whyItMatters":"Type 2 diabetes significantly increases the risk of poor bone healing and implant failure. This study reveals that the choice of diabetes medication matters for bone health — exenatide (a GLP-1 peptide drug) not only controls blood sugar but actively promotes bone formation through multiple mechanisms. This adds 'bone protection' to the growing list of GLP-1 RA benefits beyond glycemic control and could influence treatment decisions for diabetic patients needing dental or orthopedic implants.","specificNumbers":"Exenatide vs insulin vs PBS · micro-CT bone analysis · dual-fluorescent labeling · LRP5/6/GSK-3β/β-catenin Wnt pathway activated · BMPR1A suppressed (anti-lipogenesis) · β-TrCP upregulated (anti-inflammation) · T2D rat model","methodology":"In vivo: Diabetic rats received dental implants and were treated with exenatide, insulin, or PBS. Peri-implant bone was assessed by micro-CT, histology, dual-fluorescent labeling, immunofluorescence, and immunohistochemistry. In vitro: Bone marrow mesenchymal stromal cells from T2D rats were treated with exenatide, insulin, or PBS, and osteogenesis-related and Wnt signaling gene/protein expression was measured by RT-PCR and Western blotting.","limitations":"This is a rat model study, and bone biology differs between rodents and humans. The study used a T2D model with implants — results may not generalize to other bone healing scenarios. Long-term bone maintenance effects were not assessed. The exenatide doses used in rats may not translate directly to human clinical doses. The study did not compare newer GLP-1 RAs like semaglutide or tirzepatide."},{"rthcId":"RPEP-07988","title":"A post-hoc pooled analysis to evaluate efficacy and safety of insulin glargine 300 U/mL in insulin-naïve people with type 2 diabetes with/without prior use of glucagon-like peptide-1 receptor agonist therapy.","authors":"Cheng, Alice Y Y; Mauricio, Didac; Ritzel, Robert; Al-Sofiani, Mohammed E; Bailey, Timothy; Aileen Mabunay, Maria; Bonnemaire, Mireille; Melas-Melt, Lydie; Mimouni, Safia; Davies, Melanie","year":2024,"journal":"Diabetes research and clinical practice, 217, 111871","doi":"10.1016/j.diabres.2024.111871","pmid":"39343145","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07989","title":"Oxytocin treatment rescues irritability-like behavior in Cc2d1a conditional knockout mice.","authors":"Cheng, Kuan-Hsiang; Hung, Yu-Chieh; Ling, Pin; Hsu, Kuei-Sen","year":2024,"journal":"Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 49(11), 1792-1802","doi":"10.1038/s41386-024-01920-4","pmid":"39014123","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07990","title":"Proteomic Insights into the Effects of Jianweixiaoshi Tablets on Functional Dyspepsia with Spleen Deficiency in Rats.","authors":"Cheng, Xiaoying; Wan, Jianhua; Sun, Denglong; Zhan, Yang; Yu, Jingting; Li, Yingmeng; Xiong, Yanxia; Liu, Wenjun","year":2024,"journal":"Drug design, development and therapy, 18, 5129-5148","doi":"10.2147/DDDT.S477034","pmid":"39554757","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07991","title":"Effects of replacing soybean meal with enzymolysis-fermentation compound protein feed on growth performance, apparent digestibility of nutrients, carcass traits, and meat quality in growing-finishing pigs.","authors":"Cheng, Yu; He, Jun; Zheng, Ping; Yu, Jie; Pu, Junning; Huang, Zhiqing; Mao, Xiangbing; Luo, Yuheng; Luo, Junqiu; Yan, Hui; Wu, Aimin; Yu, Bing; Chen, Daiwen","year":2024,"journal":"Journal of animal science and biotechnology, 15(1), 127","doi":"10.1186/s40104-024-01080-x","pmid":"39261875","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07992","title":"The potential adverse effects of hypodermic glucagon-like peptide -1 receptor agonist on patients with type 2 diabetes: A population-based study.","authors":"Cheng, Zhiyuan; Wang, Shuang; Li, Fu-Rong; Jin, Cheng; Mo, Chunbao; Zheng, Jing; Li, Xia; Liang, Fengchao; Yang, Jinkui; Gu, Dongfeng","year":2024,"journal":"Journal of diabetes, 16(10), e70013","doi":"10.1111/1753-0407.70013","pmid":"39435881","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07993","title":"In adults with moderate-to-severe OSA and obesity, tirzepatide reduced apnea-hypopnea events vs. placebo.","authors":"Cheskin, Lawrence J; Rajagopal, Selvi","year":2024,"journal":"Annals of internal medicine, 177(10), JC116","doi":"10.7326/ANNALS-24-02174-JC","pmid":"39348697","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07994","title":"A Review of Incretin Therapies Approved and in Late-Stage Development for Overweight and Obesity Management.","authors":"Chetty, Ashwin Kanna; Rafi, Ebne; Bellini, Natalie J; Buchholz, Natalie; Isaacs, Diana","year":2024,"journal":"Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists, 30(3), 292-303","doi":"10.1016/j.eprac.2023.12.010","pmid":"38122931","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07995","title":"Pro-inflammatory activity of Cutibacterium acnes phylotype IA1 and extracellular vesicles: An in vitro study.","authors":"Cheung, Caroline T; Lancien, Ugo; Corvec, Stéphane; Mengeaud, Valérie; Mias, Céline; Véziers, Joëlle; Khammari, Amir; Dréno, Brigitte","year":2024,"journal":"Experimental dermatology, 33(8), e15150","doi":"10.1111/exd.15150","pmid":"39113601","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07996","title":"Blood pressure elevation in erenumab-treated patients with migraine: A retrospective real-world experience.","authors":"Chhabra, Nikita; Mead-Harvey, Carolyn; Dodoo, Christopher A; Iser, Courtney; Taylor, Hallie; Chaudhary, Hira; Vanood, Aimen; Dodick, David W","year":2024,"journal":"Headache, 64(3), 233-242","doi":"10.1111/head.14679","pmid":"38411625","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07997","title":"Advancing toward precision migraine treatment: Predicting responses to preventive medications with machine learning models based on patient and migraine features.","authors":"Chiang, Chia-Chun; Schwedt, Todd J; Dumkrieger, Gina; Wang, Liguo; Chao, Chieh-Ju; Ouellette, Heather A; Banerjee, Imon; Chen, Yi-Chieh; Jones, Brandon M; Burke, Krista M; Wang, Han; Murray, Ann M; Montenegro, Monique M; Stern, Jennifer I; Whealy, Mark; Kissoon, Narayan; Cutrer, Fred M","year":2024,"journal":"Headache, 64(9), 1094-1108","doi":"10.1111/head.14806","pmid":"39176658","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07998","title":"TLR4/7-mediated host-defense responses of gingival epithelial cells.","authors":"Chiba, Norika; Tada, Ryohei; Ohnishi, Tomokazu; Matsuguchi, Tetsuya","year":2024,"journal":"Journal of cellular biochemistry, 125(7), e30576","doi":"10.1002/jcb.30576","pmid":"38726711","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-07999","title":"Physical cardiac rehabilitation effects on cardio-metabolic outcomes in the patients with hypertrophic cardiomyopathy: a systematic review.","authors":"Chichagi, Fatemeh; Ghanbari-Mardasi, Kimiya; Shirsalimi, Niyousha; Sheikh, Mahboobeh; Hakim, Diaa","year":2024,"journal":"American journal of cardiovascular disease, 14(6), 330-341","doi":"10.62347/JOYM3506","pmid":"39839563","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08000","title":"The effects of high-intensity interval training and moderate-intensity continuous training on patients underwent Coronary Artery Bypass Graft surgery; a systematic review.","authors":"Chichagi, Fatemeh; Alikhani, Reyhaneh; Hosseini, Mohammad Hossein; Azadi, Kiarash; Shirsalimi, Niyousha; Ghodsi, Saeed; Jameie, Mana","year":2024,"journal":"American journal of cardiovascular disease, 14(6), 306-317","doi":"10.62347/EWMH1925","pmid":"39839564","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08001","title":"Voltage-gated Calcium Channels as Potential Therapeutic Targets in Migraine.","authors":"Chichorro, Juliana G; Gambeta, Eder; Baggio, Darciane F; Zamponi, Gerald W","year":2024,"journal":"The journal of pain, 25(8), 104514","doi":"10.1016/j.jpain.2024.03.010","pmid":"38522594","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08002","title":"Bactericidal activities and biochemical features of 16 antimicrobial peptides against bovine-mastitis causative pathogens.","authors":"Cho, Hye-Sun; Kim, Dohun; Jeon, Hyoim; Somasundaram, Prathap; Soundrarajan, Nagasundarapandian; Park, Chankyu","year":2024,"journal":"Veterinary research, 55(1), 150","doi":"10.1186/s13567-024-01402-x","pmid":"39543729","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08003","title":"Long-Term Outcome After Discontinuation of CGRP-Targeting Therapy for Migraine.","authors":"Cho, Soohyun; Kim, Byung-Kun","year":2024,"journal":"Current pain and headache reports, 28(8), 743-751","doi":"10.1007/s11916-024-01259-x","pmid":"38683278","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08004","title":"Semaglutide-induced weight loss improves mitochondrial energy efficiency in skeletal muscle.","authors":"Choi, Ran Hee; Karasawa, Takuya; Meza, Cesar A; Maschek, J Alan; Manuel, Allison; Nikolova, Linda S; Fisher-Wellmen, Kelsey H; Cox, James E; Chaix, Amandine; Funai, Katsuhiko","year":2024,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2024.11.13.623431","pmid":"39605484","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08005","title":"Cellular and metabolic function of GIRK1 potassium channels expressed by arcuate POMC and NPY/AgRP neurons.","authors":"Choi, Yeeun; Yoo, Eun-Seon; Oh, Youjin; Sohn, Jong-Woo","year":2024,"journal":"Molecules and cells, 47(11), 100122","doi":"10.1016/j.mocell.2024.100122","pmid":"39374791","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08006","title":"Exploring peptidomes of by-products generated during chhurpi production using Lactobacillus delbrueckii WS4 for identification of novel bioactive peptides.","authors":"Chourasia, Rounak; Dabrha, Gayatri; Abedin, Md Minhajul; Phukon, Loreni Chiring; Singh, Ashish Kumar; Sahoo, Dinabandhu; Singh, Sudhir P; Rai, Amit Kumar","year":2024,"journal":"Food & function, 15(11), 5987-5999","doi":"10.1039/d4fo00405a","pmid":"38742436","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08007","title":"Recent advances in the molecular signaling pathways of Substance P in Alzheimer's disease: Link to neuroinflammation associated with toll-like receptors.","authors":"Chowdari Gurram, Prasada; Satarker, Sairaj; Nampoothiri, Madhavan","year":2024,"journal":"Biochemical and biophysical research communications, 733, 150597","doi":"10.1016/j.bbrc.2024.150597","pmid":"39197195","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08008","title":"Liraglutide Improves Myocardial Perfusion and Energetics and Exercise Tolerance in Patients With Type 2 Diabetes.","authors":"Chowdhary, Amrit; Thirunavukarasu, Sharmaine; Joseph, Tobin; Jex, Nicholas; Kotha, Sindhoora; Giannoudi, Marilena; Procter, Henry; Cash, Lizette; Akkaya, Sevval; Broadbent, David; Xue, Hui; Swoboda, Peter; Valkovič, Ladislav; Kellman, Peter; Plein, Sven; Rider, Oliver J; Neubauer, Stefan; Greenwood, John P; Levelt, Eylem","year":2024,"journal":"Journal of the American College of Cardiology, 84(6), 540-557","doi":"10.1016/j.jacc.2024.04.064","pmid":"39084829","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08009","title":"Weighing your options-intragastric balloon versus semaglutide.","authors":"Choy, Kevin; Abbitt, Danielle; Kovar, Alexandra; Jones, Teresa S; McCallum, Molly; Thomas, Elizabeth A; Saxon, David R; Wikiel, Krzysztof J; Jones, Edward L","year":2024,"journal":"Surgical endoscopy, 38(10), 6070-6075","doi":"10.1007/s00464-024-11169-z","pmid":"39138683","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08010","title":"Dietary intake by patients taking GLP-1 and dual GIP/GLP-1 receptor agonists: A narrative review and discussion of research needs.","authors":"Christensen, Sandra; Robinson, Katie; Thomas, Sara; Williams, Dominique R","year":2024,"journal":"Obesity pillars, 11, 100121","doi":"10.1016/j.obpill.2024.100121","pmid":"39175746","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08011","title":"Real-world impact of adding a glucagon-like peptide-1 receptor agonist compared with basal insulin on metabolic targets in adults living with type 2 diabetes and chronic kidney disease already treated with a sodium-glucose co-transporter-2 inhibitor: The Impact GLP-1 CKD study.","authors":"Chu, Lisa; Bradley, Ryan M; Auerbach, Pernille; Abitbol, Alexander","year":2024,"journal":"Diabetes, obesity & metabolism, 26(10), 4674-4683","doi":"10.1111/dom.15834","pmid":"39113258","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08012","title":"Clinical Outcomes of Tirzepatide or GLP-1 Receptor Agonists in Individuals With Type 2 Diabetes.","authors":"Chuang, Min-Hsiang; Chen, Jui-Yi; Wang, Hsien-Yi; Jiang, Zheng-Hong; Wu, Vin-Cent","year":2024,"journal":"JAMA network open, 7(8), e2427258","doi":"10.1001/jamanetworkopen.2024.27258","pmid":"39133485","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08013","title":"A novel antioxidant iron-chelating peptide from yak skin: analysis of the chelating mechanism and digestion stability in vitro.","authors":"Ci, Xiaoman; Liu, Ran; Sun, Yuting; Rifky, Mohamed; Liu, Rui; Jin, Yan; Zhu, Qiaomei; Zhang, Min; Wu, Tao","year":2024,"journal":"Journal of the science of food and agriculture, 104(13), 7907-7916","doi":"10.1002/jsfa.13621","pmid":"38828699","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08014","title":"GLP1-GIP receptor co-agonists: a promising evolution in the treatment of type 2 diabetes.","authors":"Ciardullo, Stefano; Morieri, Mario Luca; Daniele, Giuseppe; Fiorentino, Teresa Vanessa; Mezza, Teresa; Tricò, Domenico; Consoli, Agostino; Del Prato, Stefano; Giorgino, Francesco; Piro, Salvatore; Solini, Anna; Avogaro, Angelo","year":2024,"journal":"Acta diabetologica, 61(8), 941-950","doi":"10.1007/s00592-024-02300-6","pmid":"38831203","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tirzepatide is a novel peptide that selectively binds and activates both the GIP and GLP-1 receptors. The review consolidates evidence from multiple clinical trials showing:\n\n- Tirzepatide produces superior blood sugar (HbA1c) reductions compared to GLP-1-only drugs\n- It achieves greater weight loss than existing single-target treatments\n- The dual GIP/GLP-1 mechanism provides complementary metabolic benefits\n- It is already authorized in several countries for type 2 diabetes and obesity\n\nThe GIP component adds benefits beyond what GLP-1 activation alone can achieve, including enhanced insulin secretion and potentially different effects on fat metabolism and energy expenditure.","whyItMatters":"Tirzepatide represents the most significant advance in peptide-based diabetes therapy since the introduction of GLP-1 receptor agonists. By targeting two hormone receptors, it achieves results that single-target drugs cannot match. The fact that it is already approved and prescribed makes this review practically relevant for patients and clinicians. It also sets the stage for even more complex multi-receptor peptide drugs in development.","specificNumbers":"","methodology":"This is a narrative literature review summarizing the mechanisms of action of GIP/GLP-1 co-agonists and the clinical trial data for tirzepatide. The authors reviewed data from the major clinical development programs including the SURPASS (diabetes) and SURMOUNT (obesity) trial series.","limitations":"As a narrative review, this paper synthesizes existing data without presenting new findings. The review was published relatively early in tirzepatide's clinical life, meaning some long-term safety and efficacy data were not yet available. The comparison between GIP/GLP-1 dual agonism and GLP-1 agonism alone is complicated by dose differences and study designs. The relative contribution of GIP versus GLP-1 receptor activation to tirzepatide's clinical effects is still being debated."},{"rthcId":"RPEP-08015","title":"Polycystic ovary syndrome and type 1 diabetes - the current state of knowledge.","authors":"Cichocka, Edyta; Maj-Podsiadło, Anna; Gumprecht, Janusz","year":2024,"journal":"Endokrynologia Polska, 75(5), 479-485","doi":"10.5603/ep.101392","pmid":"39376174","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08016","title":"Cardiovascular Effectiveness and Safety of Antidiabetic Drugs in Patients with Type 2 Diabetes and Peripheral Artery Disease: Systematic Review.","authors":"Cimellaro, Antonio; Cavallo, Michela; Mungo, Marialaura; Suraci, Edoardo; Spagnolo, Francesco; Addesi, Desirée; Pintaudi, Medea; Pintaudi, Carmelo","year":2024,"journal":"Medicina (Kaunas, Lithuania), 60(9)","doi":"10.3390/medicina60091542","pmid":"39336583","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08017","title":"Obesity, heart failure with preserved ejection fraction, and the role of glucagon-like peptide-1 receptor agonists.","authors":"Cimino, Giuliana; Vaduganathan, Muthiah; Lombardi, Carlo M; Pagnesi, Matteo; Vizzardi, Enrico; Tomasoni, Daniela; Adamo, Marianna; Metra, Marco; Inciardi, Riccardo M","year":2024,"journal":"ESC heart failure, 11(2), 649-661","doi":"10.1002/ehf2.14560","pmid":"38093506","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08018","title":"Integrin Facilitates the Internalization of TAT Peptide Conjugated to RGD Motif in Model Lipid Membranes.","authors":"Ciobanasu, Corina; Pernier, Julien; Le Clainche, Christophe","year":2024,"journal":"Chembiochem : a European journal of chemical biology, 25(2), e202300642","doi":"10.1002/cbic.202300642","pmid":"37947251","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08019","title":"In Situ Transglutaminase Cross-Linking Improves Mechanical Properties of Self-Assembling Peptides for Biomedical Applications.","authors":"Ciulla, Maria Gessica; Marchini, Amanda; Gazzola, Jacopo; Forouharshad, Mahdi; Pugliese, Raffaele; Gelain, Fabrizio","year":2024,"journal":"ACS applied bio materials, 7(3), 1723-1734","doi":"10.1021/acsabm.3c01148","pmid":"38346174","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Transglutaminase type 2 (TGase) enzymatic cross-linking successfully increased the stiffness and resilience of self-assembling peptide (SAP) hydrogels without reducing their maximum stress-at-failure. The enzyme creates isopeptide bonds between peptide chains, strengthening the material while maintaining its fibrous nanostructure that mimics natural tissue.\n\nCritically, the cross-linking process did not harm human neural stem cells (hNSCs) seeded within the hydrogel — cell viability and differentiation capacity were preserved, indicating that this strengthening technique could safely be performed in situ during biomedical applications.","whyItMatters":"Self-assembling peptide hydrogels are promising scaffolds for tissue repair because they naturally mimic the extracellular matrix. However, their softness limits their use in applications requiring structural support. This enzymatic approach solves that problem by making the materials stiffer without compromising their biological compatibility, opening the door to using peptide hydrogels in tissue engineering applications that require greater mechanical strength.","specificNumbers":"Improved storage modulus · No loss of stress-at-failure · hNSC viability and differentiation preserved · TGase type 2 cross-linking","methodology":"Researchers synthesized a set of self-assembling peptide sequences and cross-linked them using transglutaminase type 2. The resulting materials were characterized using rheological experiments (measuring stiffness), atomic force microscopy (imaging structure), thioflavin-T binding assay (detecting fibril formation), and infrared spectroscopy (analyzing molecular bonds). Biocompatibility was tested by seeding human neural stem cells on the cross-linked hydrogels and assessing viability and differentiation.","limitations":"This is an in vitro study; in vivo performance including degradation rates, immune response, and long-term stability has not been tested. The specific improvement in storage modulus values was not quantified in the abstract. Only neural stem cells were tested — compatibility with other cell types remains to be established."},{"rthcId":"RPEP-08020","title":"GLP-1 receptor agonists: A review of glycemic benefits and beyond.","authors":"Clark, LaDonna","year":2024,"journal":"JAAPA : official journal of the American Academy of Physician Assistants, 37(4), 1-4","doi":"10.1097/01.JAA.0001007388.97793.41","pmid":"38531038","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08021","title":"Aspects of complexity in quality and safety assessment of peptide therapeutics and peptide-related impurities. A regulatory perspective.","authors":"Colalto, Cristiano","year":2024,"journal":"Regulatory toxicology and pharmacology : RTP, 153, 105699","doi":"10.1016/j.yrtph.2024.105699","pmid":"39243929","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08022","title":"Peptide-Coated Polycaprolactone-Benzalkonium Chloride Nanocapsules for Targeted Drug Delivery to the Pancreatic β-Cell.","authors":"Collins, Jillian; Barra, Jessie M; Holcomb, Keifer; Ocampo, Andres; Fremin, Ashton; Kratz, Austin; Akolade, Jubril; Hays, Julianna K; Shilleh, Ali; Sela, Amit; Hodson, David J; Broichhagen, Johannes; Russ, Holger A; Farnsworth, Nikki L","year":2024,"journal":"ACS applied bio materials, 7(10), 6451-6466","doi":"10.1021/acsabm.4c00621","pmid":"39315885","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08023","title":"Materials derived from the human elastin-like polypeptide fusion with an antimicrobial peptide strongly promote cell adhesion.","authors":"Colomina-Alfaro, Laura; Sist, Paola; D'Andrea, Paola; Urbani, Ranieri; Marchesan, Silvia; Stamboulis, Artemis; Bandiera, Antonella","year":2024,"journal":"Journal of materials chemistry. B, 12(36), 8966-8976","doi":"10.1039/d4tb00319e","pmid":"39045800","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The HELP-hBD1 fusion biopolymer and its released active forms inhibited E. coli growth in redox environments. The fusion construct successfully produced the structurally complex human β-defensin 1, which is normally difficult to synthesize chemically due to its folding constraints.\n\nRemarkably, 2D and 3D materials derived from the biopolymer showed strong cell adhesion-promoting activity, demonstrating dual functionality: antimicrobial protection and support for tissue growth. Engineered endoproteinase recognition sites allowed release of active hBD1 forms from the fusion carrier.","whyItMatters":"Biomaterials that simultaneously fight infection and promote tissue healing address a major clinical need. Surgical implants, wound dressings, and tissue engineering scaffolds are often compromised by bacterial colonization. This polypeptide-defensin fusion combines antimicrobial defense with cell-friendly properties in a biodegradable, biocompatible material — and uses a sustainable recombinant production method.","specificNumbers":"","methodology":"The researchers designed a gene encoding human elastin-like polypeptide fused with human β-defensin 1, incorporating specific endoproteinase cleavage sites. The construct was expressed recombinantly and purified. Antimicrobial activity was tested against E. coli. 2D and 3D materials were fabricated from the biopolymer and tested for cell adhesion and cytocompatibility.","limitations":"Antimicrobial activity was demonstrated only against E. coli — testing against a broader range of pathogens, including gram-positive bacteria and fungi, would strengthen the case. The study did not include in vivo testing. The redox-dependent antimicrobial activity may limit the material's effectiveness in all tissue environments. Scale-up of recombinant production for clinical-grade materials was not addressed."},{"rthcId":"RPEP-08024","title":"Design, Synthesis, and Anti-Osteoporotic Characterization of Arginine N-Glycosylated Teriparatide Analogs via the Silver-catalyzed Solid-Phase Glycosylation Strategy.","authors":"Cong, Wei; Shen, Huaxing; Jiang, Yanan; Li, Linji; Kong, Xianglong; Chen, Si; Hu, Honggang; Li, Xiang","year":2024,"journal":"Journal of medicinal chemistry, 67(2), 1360-1369","doi":"10.1021/acs.jmedchem.3c01903","pmid":"38195392","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08025","title":"Semaglutide Inducing Resolution of Proliferative Diabetic Retinopathy: A Case Report.","authors":"Cool, Daniel; Coventon, James; Sharma, Abhishek","year":2024,"journal":"Case reports in ophthalmological medicine, 2024, 5834769","doi":"10.1155/crop/5834769","pmid":"39691771","tags":[],"studyType":"case-report","evidenceStrength":"very-low","keyFinding":"A 47-year-old woman with type 2 diabetes and proliferative diabetic retinopathy (PDR) showed resolution of new blood vessel growth in her right eye and improved diabetic macular oedema within just 6 weeks of starting semaglutide therapy. Notably, this improvement occurred despite minimal changes in her blood sugar control, suggesting semaglutide may have a direct, independent effect on diabetic eye disease beyond its glucose-lowering properties.","whyItMatters":"Proliferative diabetic retinopathy is a sight-threatening complication of diabetes that typically requires laser treatment or eye injections. If semaglutide can independently reverse this condition — not just through better blood sugar control — it would represent an unexpected and significant additional benefit of GLP-1 therapy for the millions of diabetics at risk of vision loss.","specificNumbers":"1 patient · 47 years old · Resolution within 6 weeks · Minimal glycaemic change","methodology":"Single case report describing a 47-year-old woman with type 2 diabetes, obesity, hypertension, and dyslipidaemia who had PDR in her right eye and severe nonproliferative diabetic retinopathy in her left eye. After starting semaglutide (originally prescribed for diabetes/weight management), her retinopathy was reassessed clinically.","limitations":"This is a single case report — the lowest level of clinical evidence. It cannot establish causation, and the improvement could be coincidental or due to other factors not controlled for. Large controlled studies are needed to confirm any direct retinal effect of semaglutide."},{"rthcId":"RPEP-08026","title":"Exploring biocompatible chemistry to create stapled and photoswitchable variants of the antimicrobial peptide aurein 1.2.","authors":"Coram, Alexandra E; Morewood, Richard; Voss, Saan; Price, Joshua L; Nitsche, Christoph","year":2024,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 30(4), e3551","doi":"10.1002/psc.3551","pmid":"37926859","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08027","title":"Host defense peptides in crocodilians - A comprehensive review.","authors":"Cordero Gil, Trinidad de Los Ángeles; Moleón, María Soledad; Marelli, Belkis Ester; Siroski, Pablo Ariel","year":2024,"journal":"Peptides, 182, 171312","doi":"10.1016/j.peptides.2024.171312","pmid":"39471969","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Several families of host defense peptides (HDPs) have been identified in crocodilians:\n- Cathelicidins — broad-spectrum antimicrobial peptides\n- Beta-defensins — cysteine-rich antimicrobial/immune signaling peptides\n- Hepcidins — iron-regulatory antimicrobial peptides\n- Leucrocins — crocodilian-specific antimicrobial peptides\n- Hemocidins — hemoglobin-derived antimicrobial fragments\n- Omwaprins — wasp venom-like antimicrobial peptides found in crocodilians\n\nThese peptides collectively exhibit antimicrobial, anti-biofilm, antifungal, and anticancer activities. Crocodilian plasma has superior hemolytic capacity compared to other organisms, contributing to their exceptional wound-healing and infection resistance. The slow evolutionary rate of crocodilians means these defense mechanisms are highly conserved and well-optimized.","whyItMatters":"Antibiotic resistance is one of the greatest global health threats, and new antimicrobial agents are desperately needed. Crocodilians represent an underexplored but extraordinary source of antimicrobial peptides, having survived for over 200 million years in some of the most pathogen-rich environments on Earth. Their diverse peptide defense systems — refined by hundreds of millions of years of evolution — offer a natural library of compounds that can be modified and optimized for human therapeutic use.","specificNumbers":"","methodology":"Comprehensive narrative review of published research on crocodilian host defense peptides, including peptide identification, structural characterization (sequence and 3D conformation), mechanism of action studies, and bioinformatics approaches to enhancing native peptide activity. The review covers both experimental studies and computational predictions.","limitations":"Most crocodilian HDPs have been characterized only in vitro; in vivo therapeutic validation in mammalian models is limited. The transition from natural crocodilian peptides to human therapeutics faces challenges including stability, toxicity, and manufacturing cost. Not all crocodilian species have been equally studied, and peptide diversity likely extends beyond what has been cataloged. The review acknowledges that peptide drug development historically has high attrition rates."},{"rthcId":"RPEP-08028","title":"Heart failure biomarkers and prediction of early left ventricle remodeling after acute coronary syndromes.","authors":"Cordero, Alberto; Velasco, Irene; Flores, Emilio; López-Ayala, José Mª; Sánchez-Munuera, Sonia; Muñoz-Villalba, Mª Pilar; Selva-Mora, Alejandro; Galán-Giménez, Francisco; de la Espriella, Rafael; Nuñez, Julio","year":2024,"journal":"Clinical biochemistry, 131-132, 110814","doi":"10.1016/j.clinbiochem.2024.110814","pmid":"39218335","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08029","title":"Transformation of G1-G2 neuroendocrine tumors to neuroendocrine carcinomas following peptide receptor radionuclide therapy.","authors":"Cordero-Hernandez, Igryl S; Ross, Alicia C; Dasari, Arvind; Halperin, Daniel M; Chasen, Beth; Yao, James C","year":2024,"journal":"Endocrine-related cancer, 31(4)","doi":"10.1530/ERC-23-0203","pmid":"38329269","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08030","title":"Tirzepatide against obesity and insulin-resistance: pathophysiological aspects and clinical evidence.","authors":"Corrao, Salvatore; Pollicino, Chiara; Maggio, Dalila; Torres, Alessandra; Argano, Christiano","year":2024,"journal":"Frontiers in endocrinology, 15, 1402583","doi":"10.3389/fendo.2024.1402583","pmid":"38978621","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08031","title":"Sustained metabolic benefits of ΔTRTX-Ac1, a tarantula venom-derived peptide, when administered together with exenatide in high-fat fed mice.","authors":"Coulter-Parkhill, Aimee; Tanday, Neil; Cobice, Diego; McLaughlin, Christopher M; McClean, Stephen; Gault, Victor A; Irwin, Nigel","year":2024,"journal":"Diabetes, obesity & metabolism, 26(1), 329-338","doi":"10.1111/dom.15319","pmid":"37818589","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08032","title":"Research Note: Intestinal avian defensin 2 and robustness of chicks.","authors":"Coustard, Sonia Métayer; Rossignol, Christelle; Collin, Anne; Blanc, Fany; Lallier, Nathalie; Schouler, Catherine; Duval, Elisabeth Le Bihan; Travel, Angelique; Lalmanach, Anne-Christine","year":2024,"journal":"Poultry science, 103(1), 103175","doi":"10.1016/j.psj.2023.103175","pmid":"38029604","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08033","title":"Progress and challenges in glypican-3 targeting for hepatocellular carcinoma therapy.","authors":"Couzinet, Arnaud; Suzuki, Toshihiro; Nakatsura, Tetsuya","year":2024,"journal":"Expert opinion on therapeutic targets, 28(10), 895-909","doi":"10.1080/14728222.2024.2416975","pmid":"39428649","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GPC3 is confirmed as an ideal cancer antigen for hepatocellular carcinoma (HCC) immunotherapy due to its high expression on tumor cells and limited expression in normal adult tissues. The GPC3 peptide vaccine developed by the authors has progressed from preclinical studies through first-in-human clinical trials.\n\nIn resectable HCC, the combination of immune checkpoint inhibitors and GPC3-targeted cancer vaccines appears promising as prophylactic adjuvant therapy to prevent recurrence. However, in advanced HCC, clinical trials across multiple modalities (peptide vaccines, antibody therapy, CAR-T/TCR-T cell therapy) have not demonstrated sufficient anti-tumor efficacy — a disconnect from the encouraging preclinical data that the field must address through reverse translation research.","whyItMatters":"Liver cancer (HCC) is among the deadliest cancers worldwide, and treatment options for advanced disease remain limited. GPC3's tumor-specific expression makes it one of the most promising targets for cancer immunotherapy, and the fact that a peptide vaccine has already reached human clinical trials demonstrates real translational progress. Understanding why these therapies work better early in the disease could reshape how liver cancer patients receive treatment.","specificNumbers":"","methodology":"This is a comprehensive review article from researchers with direct experience developing and clinically testing GPC3 peptide vaccines. They surveyed the landscape of GPC3-targeting immunotherapies by focusing on clinical trial results across multiple treatment modalities: peptide vaccines, mRNA vaccines, antibody therapy, and chimeric antigen receptor (CAR) and T-cell receptor (TCR) engineered T-cell therapies for hepatocellular carcinoma.","limitations":"As a review article, this paper synthesizes existing evidence rather than presenting new data. The authors are developers of the GPC3 peptide vaccine, which could introduce bias toward their therapeutic approach. The review focuses primarily on HCC and may not fully represent GPC3-targeting efforts in other cancer types where GPC3 is also expressed."},{"rthcId":"RPEP-08034","title":"Effect of anti-CGRP-targeted therapy on migraine aura: Results of an observational case series study.","authors":"Cresta, Elena; Bellotti, Alessia; Rinaldi, Giovanni; Corbelli, Ilenia; Sarchielli, Paola","year":2024,"journal":"CNS neuroscience & therapeutics, 30(2), e14595","doi":"10.1111/cns.14595","pmid":"38332541","tags":["CGRP","migraine"],"studyType":"observational","evidenceStrength":"low-moderate","keyFinding":"Anti-CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab) significantly reduced headache days, migraine-without-aura days, acute medication use, and disability scores (MIDAS and HIT-6) over one year (p < 0.0001). However, these drugs did not reduce the frequency of migraine-with-aura attacks.\n\nInterestingly, while aura episodes kept occurring at the same rate, the headache that normally follows the aura became less intense and shorter — and some patients experienced aura attacks with no headache at all.\n\nThe researchers propose that anti-CGRP antibodies work by blocking pain signaling in the trigeminal nerve pathway (a peripheral mechanism) but cannot stop cortical spreading depression — the wave of brain activity that causes the visual and sensory disturbances of aura.","whyItMatters":"Migraine with aura affects about a third of migraine sufferers, yet most anti-CGRP drug trials have focused on migraine without aura. This study provides early clinical evidence that while these drugs effectively reduce headache pain, they don't prevent aura itself — suggesting aura and headache may be separable processes with different underlying mechanisms.","specificNumbers":"n=12 · p<0.0001 for headache days, medication days, MIDAS, HIT-6 · 1-year treatment period","methodology":"Observational case series of 12 migraine patients treated with anti-CGRP monoclonal antibodies (7 on erenumab, 2 on fremanezumab, 3 on galcanezumab) over 1 year. Data were collected at baseline (3 months prior to treatment) and every 3 months. Outcomes included headache days, migraine days, aura frequency, medication use, MIDAS disability scores, and HIT-6 impact scores.","limitations":"Very small sample size (12 patients) without a control group. As an observational case series, it cannot establish causation. The lack of randomization and blinding means placebo effects cannot be ruled out. Results should be considered hypothesis-generating rather than definitive."},{"rthcId":"RPEP-08035","title":"A multicenter, open-label long-term safety study of rimegepant for the acute treatment of migraine.","authors":"Croop, Robert; Berman, Gary; Kudrow, David; Mullin, Kathleen; Thiry, Alexandra; Lovegren, Meghan; L'Italien, Gilbert; Lipton, Richard B","year":2024,"journal":"Cephalalgia : an international journal of headache, 44(4), 3331024241232944","doi":"10.1177/03331024241232944","pmid":"38659334","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08036","title":"Bioequivalence of rimegepant, a small molecule CGRP receptor antagonist, administered as an oral tablet, a sublingual orally disintegrating tablet, and a supralingual orally disintegrating tablet: two phase 1 randomized studies in healthy adults.","authors":"Croop, Robert; Bhardwaj, Rajinder; Anderson, Matt S; Matschke, Kyle T; Hould, Jennifer; Bertz, Richard; Liu, Jing; Lipton, Richard B","year":2024,"journal":"Cephalalgia : an international journal of headache, 44(2), 3331024231219505","doi":"10.1177/03331024231219505","pmid":"38366390","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Two phase 1 randomized studies in healthy adults demonstrated that rimegepant 75 mg orally disintegrating tablet (ODT) is bioequivalent to the 75 mg oral tablet:\n\n- Sublingual ODT vs. oral tablet: AUC0-t ratio 97%, AUC0-inf ratio 97%, Cmax ratio 105% — all 90% CIs within the 80-125% bioequivalence range\n- Supralingual ODT vs. oral tablet: AUC0-t ratio 98%, AUC0-inf ratio 98%, Cmax ratio 103% — all within bioequivalence criteria\n\nBoth delivery methods achieved equivalent drug exposure, confirming the ODT formulation provides consistent absorption regardless of whether it's placed under or on top of the tongue.","whyItMatters":"For migraine patients who may experience nausea or difficulty swallowing during an attack, a dissolving tablet that works without water is a meaningful practical advantage. Confirming bioequivalence ensures patients get the same therapeutic benefit from the more convenient formulation.","specificNumbers":"","methodology":"Two single-center, phase 1, open-label, randomized bioequivalence studies in healthy adult non-smokers aged 18-55 years. One study compared sublingual ODT to oral tablet; the other compared supralingual ODT to oral tablet. Pharmacokinetic parameters measured included AUC0-t, AUC0-inf, and Cmax, with bioequivalence defined as 90% confidence intervals within the 80-125% range.","limitations":"Studies were conducted in healthy volunteers, not migraine patients during attacks. Absorption during a migraine (when gastric motility may be altered) was not assessed. The studies were open-label. Only single doses were evaluated; steady-state bioequivalence for preventive use was not tested."},{"rthcId":"RPEP-08037","title":"Tissue nano-transfection of antimicrobial genes drives bacterial biofilm killing in wounds and is potentially mediated by extracellular vesicles.","authors":"Cuellar-Gaviria, Tatiana Z; Rincon-Benavides, Maria Angelica; Halipci Topsakal, Hatice Nur; Salazar-Puerta, Ana Isabel; Jaramillo-Garrido, Shara; Kordowski, Mia; Vasquez-Martinez, Carlos A; Nguyen, Kim Truc; Rima, Xilal Y; Rana, Pranav S J B; Combita-Heredia, Orlando; Deng, Binbin; Dathathreya, Kavya; McComb, David W; Reategui, Eduardo; Wozniak, Daniel; Higuita-Castro, Natalia; Gallego-Perez, Daniel","year":2024,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 376, 1300-1315","doi":"10.1016/j.jconrel.2024.10.071","pmid":"39491627","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08038","title":"Immunologic Effects of a Novel Bovine Lactoferrin-Derived Peptide on the Gut and Clinical Perspectives.","authors":"Cui, Haiyue; Yang, Huan; Qi, Xiaoxi; Zhao, Yang; Huang, Tianle; Miao, Liguang","year":2024,"journal":"Veterinary sciences, 11(11)","doi":"10.3390/vetsci11110545","pmid":"39591319","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08039","title":"Efficacy and Molecular Mechanism of Quercetin on Constipation Induced by Berberine via Regulating Gut Microbiota.","authors":"Cui, Mengyao; Li, Ying; Zheng, Tingting; Chen, Huan; Wang, Jinrui; Feng, Yifan; Ye, Hanyi; Dong, Zhengqi; Li, Geng","year":2024,"journal":"International journal of molecular sciences, 25(11)","doi":"10.3390/ijms25116228","pmid":"38892414","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08040","title":"Initial Exploration of the In Vitro Activation of GLP-1 and GIP Receptors and Pancreatic Islet Cell Protection by Salmon-Derived Bioactive Peptides.","authors":"Currie, Crawford; Bjerknes, Christian; Framroze, Bomi","year":2024,"journal":"Marine drugs, 22(11)","doi":"10.3390/md22110490","pmid":"39590770","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08041","title":"Local and Systemic Peptide Therapies for Soft Tissue Regeneration: A Narrative Review.","authors":"Cushman, Caroline J; Ibrahim, Andrew F; Smith, Alexander D; Hernandez, Evan J; MacKay, Brendan; Zumwalt, Mimi","year":2024,"journal":"The Yale journal of biology and medicine, 97(3), 399-413","doi":"10.59249/TKNM3388","pmid":"39351323","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identified multiple peptides demonstrating efficacy in soft tissue repair across oral and intra-articular delivery routes. Intra-articular (joint injection) peptides provided localized therapeutic effects directly at the injury site, while oral peptides offered systemic benefits that could support broader tissue healing.\n\nBoth routes showed distinct advantages: joint injections bypass digestive breakdown but are more invasive and require clinical visits, while oral peptides are convenient but face significant bioavailability and absorption challenges in the gut. The field remains in its early stages, with most evidence coming from preclinical studies and limited human trials. The review positions peptide treatments as promising pre-surgical alternatives for soft tissue regeneration.","whyItMatters":"Soft tissue injuries in joints are a massive health burden — osteoarthritis alone affects over 500 million people worldwide. Current options range from anti-inflammatory drugs (which manage symptoms but don't heal tissue) to surgery (which is invasive and costly). Peptide therapies that could actually regenerate damaged tissue represent a paradigm shift from managing pain to reversing damage, potentially reducing the need for joint replacement surgery.","specificNumbers":"","methodology":"Researchers conducted a comprehensive PubMed literature search using MeSH terms related to peptide therapy, soft tissue regeneration, and routes of administration. They applied inclusion criteria focusing on mechanisms of action, clinical or biochemical outcomes, and review articles. Studies with insufficient evidence or that did not meet set evidence levels were excluded. The results were synthesized as a narrative review covering oral peptide agents, intra-articular peptide agents, and emerging human trial developments.","limitations":"As a narrative review, this paper does not include meta-analysis or systematic evidence grading. The field is still in early stages, so much of the reviewed evidence comes from preclinical studies rather than large human clinical trials. The review did not specify which individual peptides were most effective or compare them head-to-head. Publication bias may favor positive results."},{"rthcId":"RPEP-08042","title":"The effect of incretin-based drugs on the riks of acute pancreatitis: a review.","authors":"Czaplicka, Agata; Kaleta, Beata","year":2024,"journal":"Journal of diabetes and metabolic disorders, 23(1), 487-495","doi":"10.1007/s40200-024-01430-6","pmid":"38932809","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08043","title":"REAL life study of subcutaneous SEMaglutide in patients with type 2 diabetes in SPain: Ambispective, multicenter clinical study. Results in the GLP1-experienced cohort.","authors":"Cárdenas-Salas, Jersy Jair; Sierra Poyatos, Roberto Miguel; Luca, Bogdana Luiza; Sánchez Lechuga, Begoña; Modroño Móstoles, Naiara; Montoya Álvarez, Teresa; Gómez Montes, María de la Paz; Ruiz Sánchez, Jorge Gabriel; Meneses González, Diego; Sánchez-Lopez, Raquel; Casado Cases, Carlos; Pérez de Arenaza Pozo, Víctor; Vázquez Martínez, Clotilde","year":2024,"journal":"Journal of diabetes and its complications, 38(12), 108874","doi":"10.1016/j.jdiacomp.2024.108874","pmid":"39442257","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08044","title":"Cagrilintide: A Long-Acting Amylin Analog for the Treatment of Obesity.","authors":"D'Ascanio, Antonella M; Mullally, Jamie A; Frishman, William H","year":2024,"journal":"Cardiology in review, 32(1), 83-90","doi":"10.1097/CRD.0000000000000513","pmid":"36883831","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Cagrilintide is a long-acting analog of amylin, which reduces appetite through both homeostatic (hunger-regulating) and hedonic (pleasure/reward) brain pathways. Combined with semaglutide (a GLP-1 receptor agonist that reduces appetite via hypothalamic GLP-1 receptors, increases insulin, reduces glucagon, and delays gastric emptying), the two peptides have separate but complementary mechanisms that produce additive appetite reduction.\n\nClinical trials have demonstrated promising weight loss with both cagrilintide alone and the cagrilintide-semaglutide combination, supporting further development of this dual-peptide approach for sustained weight management.","whyItMatters":"Obesity affects over a billion people worldwide and has limited pharmacological treatment options between lifestyle changes and bariatric surgery. While GLP-1 drugs like semaglutide have been transformative, many patients don't achieve sufficient weight loss with single-agent therapy. The cagrilintide-semaglutide combination targets obesity's heterogeneous pathophysiology more comprehensively, potentially helping more patients achieve clinically meaningful weight loss.","specificNumbers":"","methodology":"This is a review article summarizing the pharmacology of cagrilintide and semaglutide, their mechanisms of action, and clinical trial results. The review examines amylin biology, GLP-1 receptor agonist pharmacology, and the rationale for combining these two peptide classes for obesity treatment.","limitations":"This review was published before large-scale phase 3 trial results were available for the combination therapy. Long-term safety and efficacy data beyond trial durations are not available. Whether the combination's benefits outweigh additional costs and potential side effects compared to semaglutide alone is not fully established. The additive effects described may not translate to proportionally greater weight loss in all patient populations. Injection burden increases with combination therapy."},{"rthcId":"RPEP-08045","title":"GLP-1, GIP, and Glucagon Agonists for Obesity Treatment: A Hunger Perspective.","authors":"D'Ávila, Mateus; Hall, Samantha; Horvath, Tamas L","year":2024,"journal":"Endocrinology, 165(11)","doi":"10.1210/endocr/bqae128","pmid":"39301751","tags":[],"studyType":"perspective","evidenceStrength":"very low","keyFinding":"This perspective article argues that while mono, dual, and triple agonists of GLP-1, GIP, and glucagon receptors produce impressive weight loss, fundamental biological principles about hunger and satiety raise important questions that go beyond currently reported side effects. The authors contend that suppressing hunger through pharmacology does not bypass the complex goal-oriented behaviors, systemic metabolism, and cellular metabolic processes that govern how the body regulates energy balance. They caution against treating these drugs as a simple silver bullet for obesity without understanding the deeper biological implications of overriding the hunger-satiety system.","whyItMatters":"As GLP-1-based obesity drugs become among the most widely prescribed medications in history, this perspective serves as a scientific counterweight to uncritical enthusiasm. The authors highlight that appetite regulation involves deeply interconnected systems — from cellular metabolism to complex behaviors — and that pharmacologically suppressing hunger may have consequences we don't yet fully understand. These are important considerations as dual and triple agonists push weight loss even further.","specificNumbers":"","methodology":"This is a perspective article reflecting on the biology of hunger and satiety in the context of incretin-based obesity therapies. It synthesizes existing knowledge about GLP-1, GIP, and glucagon receptor signaling rather than presenting original experimental data.","limitations":"As a perspective piece, this article presents the authors' viewpoint rather than systematic evidence. It does not perform a structured review or meta-analysis of the existing literature. The concerns raised are theoretical and biological in nature, not backed by new clinical data demonstrating specific harms."},{"rthcId":"RPEP-08046","title":"GLP-1 and GIP agonism has no direct actions in human hepatocytes or hepatic stellate cells.","authors":"da Silva Lima, Natália; Cabaleiro, Alba; Novoa, Eva; Riobello, Cristina; Knerr, Patrick J; He, Yantao; Esquinas-Román, Eva M; González-García, Ismael; Prevot, Vincent; Schwaninger, Markus; Dieguez, Carlos; López, Miguel; Müller, Timo D; Varela-Rey, Marta; Douros, Jonathan D; Nogueiras, Ruben","year":2024,"journal":"Cellular and molecular life sciences : CMLS, 81(1), 468","doi":"10.1007/s00018-024-05507-6","pmid":"39607493","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08047","title":"Semaglutide-Induced Acute Pancreatitis Leading to Death After Four Years of Use.","authors":"Dagher, Chebly; Jailani, Mohamed; Akiki, Maria; Siddique, Talha; Saleh, Zidan; Nadler, Evan","year":2024,"journal":"Cureus, 16(9), e69704","doi":"10.7759/cureus.69704","pmid":"39429379","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08048","title":"Exploring the Anxiolytic Potential of NPY by a Dipeptidyl Peptidase-IV Inhibitor in an Animal Model of PTSD.","authors":"Dahan, Matan; Zohar, Joseph; Todder, Doron; Mathé, Aleksander A; Cohen, Hagit","year":2024,"journal":"The international journal of neuropsychopharmacology, 27(12)","doi":"10.1093/ijnp/pyae062","pmid":"39626016","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08049","title":"Subthreshold activation of the melanocortin system causes generalized sensitization to anorectic agents in mice.","authors":"Dahir, Naima S; Gui, Yijun; Wu, Yanan; Sweeney, Patrick R; Rouault, Alix Aj; Williams, Savannah Y; Gimenez, Luis E; Sawyer, Tomi K; Joy, Stephen T; Mapp, Anna K; Cone, Roger D","year":2024,"journal":"The Journal of clinical investigation, 134(14)","doi":"10.1172/JCI178250","pmid":"39007271","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08050","title":"Comparative cardiovascular and renal outcomes of Liraglutide versus Dulaglutide in Asian type 2 diabetes patients.","authors":"Dai, Jhih-Wei; Lin, Yuan; Li, Xiu-Wei; Tseng, Chin-Ju; Tsai, Ming-Lung; Yang, Ning-I; Hung, Ming-Jui; Chen, Tien-Hsing","year":2024,"journal":"Scientific reports, 14(1), 27491","doi":"10.1038/s41598-024-79255-9","pmid":"39528690","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08051","title":"Efficacy of Glucagon-like Peptide-1 Receptor Agonists in Overweight/Obese and/or T2DM Adolescents: A Meta-analysis Based on Randomized Controlled Trials.","authors":"Dai, Min; Dai, Senjie; Gu, Lihu; Xiang, Zhiyi; Xu, Anyi; Lu, Siyu; Yang, Yang; Zhou, Cong","year":2024,"journal":"Journal of clinical research in pediatric endocrinology, 16(3), 323-333","doi":"10.4274/jcrpe.galenos.2024.2024-1-5","pmid":"38828884","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08052","title":"3D printable gelatin/nisin biomaterial inks for antimicrobial tissue engineering applications.","authors":"Dallos Ortega, Mateo; Aveyard, Jenny; Ciupa, Alexander; Poole, Robert J; Whetnall, David; Behnsen, Julia G; D'Sa, Raechelle A","year":2024,"journal":"Materials advances, 5(19), 7729-7746","doi":"10.1039/d4ma00544a","pmid":"39267949","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08053","title":"Mechanism-Based Macrocyclic Inhibitors of Serine Proteases.","authors":"Damalanka, Vishnu C; Banas, Victoria; De Bona, Paolo; Kashipathy, Maithri M; Battaile, Kevin; Lovell, Scott; Janetka, James W","year":2024,"journal":"Journal of medicinal chemistry, 67(6), 4833-4854","doi":"10.1021/acs.jmedchem.3c02388","pmid":"38477709","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08054","title":"Influence of maternal nutrition and one-carbon metabolites supplementation on bovine antimicrobial peptides in fetal and maternal tissues.","authors":"Daneshi, Mojtaba; Borowicz, Pawel P; Hirchert, Mara R; Entzie, Yssi L; Syring, Jessica G; King, Layla E; Safain, Kazi Sarjana; Anas, Muhammad; Reynolds, Lawrence P; Ward, Alison K; Dahlen, Carl R; Crouse, Matthew S; Caton, Joel S","year":2024,"journal":"Frontiers in veterinary science, 11, 1505427","doi":"10.3389/fvets.2024.1505427","pmid":"39720407","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08055","title":"Macrocyclic peptides derived from AcPHF6* and AcPHF6 to selectively modulate the Tau aggregation.","authors":"Dangi, Abha; Qureshi, Tazeen; Chinnathambi, Subashchandrabose; Kiran Marelli, Udaya","year":2024,"journal":"Bioorganic chemistry, 151, 107625","doi":"10.1016/j.bioorg.2024.107625","pmid":"39013241","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08056","title":"Efficacy of galcanezumab in migraine central sensitization.","authors":"Danno, Daisuke; Imai, Noboru; Kitamura, Shigekazu; Ishizaki, Kumiko; Kikui, Shoji; Takeshima, Takao","year":2024,"journal":"Scientific reports, 14(1), 21824","doi":"10.1038/s41598-024-72282-6","pmid":"39294310","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08057","title":"Glucagon-like peptide-1 analog, liraglutide, regulates Sertoli cell energy metabolism.","authors":"Dasso, Marina Ercilia; Centola, Cecilia Lucia; Galardo, María Noel; Meroni, Silvina Beatriz; Riera, María Fernanda","year":2024,"journal":"The Journal of endocrinology, 263(3)","doi":"10.1530/JOE-24-0274","pmid":"39303739","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08058","title":"Single-Center Experience of Using Liraglutide in Adolescents With Obesity +/- Type 2 Diabetes.","authors":"Dauleh, Hajar; Pasha, Maheen; Gad, Hoda; Haris, Basma; Petrovski, Goran; Afyouni, Houda; Khalifa, Amal; Shehzad, Saira; Amin, Rasha; Chirayath, Shiga; Mohamadsalih, Ghassan; Mohammed, Shayma; Malik, Rayaz A; Hussain, Khalid","year":2024,"journal":"Cureus, 16(4), e58720","doi":"10.7759/cureus.58720","pmid":"38779269","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08059","title":"High pressure-assisted enzymatic hydrolysis potentiates the production of quinoa protein hydrolysates with antioxidant and ACE-inhibitory activities.","authors":"de Carvalho Oliveira, Ludmilla; Martinez-Villaluenga, Cristina; Frias, Juana; Elena Cartea, María; Francisco, Marta; Cristianini, Marcelo; Peñas, Elena","year":2024,"journal":"Food chemistry, 447, 138887","doi":"10.1016/j.foodchem.2024.138887","pmid":"38492299","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"High hydrostatic pressure (HHP) at 300 MPa combined with Alcalase enzyme digestion produced the most potent quinoa protein hydrolysates. These showed the highest ACE-inhibitory activity (anti-hypertensive potential), enhanced antioxidant activity, and 1.8-fold increase in total flavonoids compared to non-hydrolyzed quinoa protein isolate. Three specific peptide sequences — GSHWPFGGK, FSIAWPR, and PWLNFK — had the highest Peptide Ranker scores and were predicted to have ACE-inhibitory, DPP-IV inhibitory, and antioxidant activities. Pressure at 300-400 MPa caused more extensive protein breakdown than enzyme alone.","whyItMatters":"This study demonstrates a novel food processing technique (high-pressure-assisted enzymatic hydrolysis) that can significantly boost the bioactive peptide content of quinoa — a protein-rich grain increasingly popular in Western diets. The resulting peptides showed blood-pressure-lowering and antioxidant potential, suggesting quinoa protein hydrolysates could become functional food ingredients.","specificNumbers":"200–400 MPa pressure range · 300 MPa optimal for ACE inhibition · 1.8-fold increase in total flavonoids · 3 top peptide sequences identified · Alcalase enzyme · Both ACE-inhibitory + DPP-IV inhibitory + antioxidant","methodology":"Quinoa protein isolate was subjected to enzymatic hydrolysis with Alcalase at different high hydrostatic pressure levels (200, 300, 400 MPa) and compared to non-pressurized hydrolysis and non-hydrolyzed controls. Products were analyzed by SDS-PAGE, degree of hydrolysis, phenolic content, antioxidant assays, ACE inhibition assays, and peptide sequencing with Peptide Ranker prediction of bioactivity.","limitations":"This is entirely an in vitro food chemistry study. The ACE-inhibitory and DPP-IV inhibitory activities were measured in lab assays, not in living organisms. Whether the identified peptides survive human digestion and absorption intact is unknown. Peptide Ranker predictions are computational — not experimental validation of bioactivity. The study doesn't address taste, palatability, or practical food formulation."},{"rthcId":"RPEP-08060","title":"12-month neurological and psychiatric outcomes of semaglutide use for type 2 diabetes: a propensity-score matched cohort study.","authors":"De Giorgi, Riccardo; Koychev, Ivan; Adler, Amanda I; Cowen, Philip J; Harmer, Catherine J; Harrison, Paul J; Taquet, Maxime","year":2024,"journal":"EClinicalMedicine, 74, 102726","doi":"10.1016/j.eclinm.2024.102726","pmid":"39764175","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide was not associated with increased risk of any of 22 neurological or psychiatric outcomes over 12 months compared to three other diabetes medications. Instead, it was associated with significantly reduced risk of cognitive deficit (HR 0.72, 95% CI 0.64–0.80 vs sitagliptin; HR 0.72, 95% CI 0.63–0.81 vs glipizide), dementia (HR 0.52, 95% CI 0.40–0.68 vs sitagliptin), and nicotine misuse (HR 0.72, 95% CI 0.61–0.85 vs glipizide; HR 0.77, 95% CI 0.65–0.90 vs empagliflozin). No differences were observed in negative control outcomes, strengthening confidence in the findings.","whyItMatters":"Concerns about suicidality and other neuropsychiatric side effects have dogged GLP-1 receptor agonists. This large-scale study not only found no increased neuropsychiatric risk with semaglutide but discovered potential protective effects on cognition and addiction — findings that could expand semaglutide's therapeutic applications if confirmed in clinical trials.","specificNumbers":"n=23,386 matched pairs (vs sitagliptin) · n=22,584 (vs empagliflozin) · n=19,206 (vs glipizide) · cognitive deficit HR 0.72 · dementia HR 0.52 · nicotine misuse HR 0.72–0.82 · 22 outcomes assessed · 12-month follow-up","methodology":"Retrospective cohort study using TriNetX US Collaborative Network electronic health records covering over 100 million patients. Three propensity-score matched cohorts (1:1) compared semaglutide users with type 2 diabetes to users of sitagliptin, empagliflozin, or glipizide prescribed between December 2017 and May 2021. Cox regression assessed 22 neurological and psychiatric outcomes over 12 months. Negative control outcomes were used to detect unmeasured confounding. Multiple-testing correction was applied.","limitations":"Retrospective observational design cannot prove causation. The study relied on electronic health records, which may undercount diagnoses not coded in routine care. The exploratory nature meant no pre-registered protocol. The cohort was U.S.-based and may not generalize globally. Some comparisons lost significance after multiple-testing correction."},{"rthcId":"RPEP-08061","title":"Multifunctional properties of peptides derived from black cricket (Gryllus assimilis) and effects of in vitro digestion simulation on their bioactivities.","authors":"de Matos, Francielle Miranda; Rasera, Gabriela Boscariol; de Castro, Ruann Janser Soares","year":2024,"journal":"Food research international (Ottawa, Ont.), 196, 115134","doi":"10.1016/j.foodres.2024.115134","pmid":"39614589","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08062","title":"Is calcitonin gene-related peptide (CGRP) the missing link in food histamine-induced migraine? A review of functional gut-to-trigeminovascular system connections.","authors":"de Mora, Fernando; Messlinger, Karl","year":2024,"journal":"Drug discovery today, 29(4), 103941","doi":"10.1016/j.drudis.2024.103941","pmid":"38447930","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08063","title":"Liraglutide for the Treatment of Weight Regain After Bariatric Surgery: A Systematic Review and Meta-analysis.","authors":"de Moraes, Francisco Cezar Aquino; Morbach, Victoria; Sano, Vitor Kendi Tsuchiya; Fernandes, Lilianne Rodrigues; Kreuz, Michele; Kelly, Francinny Alves","year":2024,"journal":"Obesity surgery, 34(8), 2844-2853","doi":"10.1007/s11695-024-07384-1","pmid":"38987454","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08064","title":"Semaglutide Attenuates Anxious and Depressive-Like Behaviors and Reverses the Cognitive Impairment in a Type 2 Diabetes Mellitus Mouse Model Via the Microbiota-Gut-Brain Axis.","authors":"de Paiva, Igor Henrique Rodrigues; da Silva, Rodrigo Soares; Mendonça, Ingrid Prata; de Souza, José Roberto Botelho; Peixoto, Christina Alves","year":2024,"journal":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology, 19(1), 36","doi":"10.1007/s11481-024-10142-w","pmid":"39042202","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08065","title":"Metabolic Tumor Volume on 18-Fluorodeoxyglucose Positron Emission Tomography as a Prognostic Marker of Survival in Patients With Locally Advanced or Metastatic Neuroendocrine Neoplasms Treated With 177Lutetium-DOTA-Octreotate Peptide Receptor Radionuclide Therapy.","authors":"De Silva, Madhawa K; Chan, David L H; Bernard, Elizabeth J; Conner, Alice J; Mascall, Sophie L; Bailey, Dale L; Roach, Paul J; Clarke, Stephen J; Diakos, Connie I; Pavlakis, Nick; Schembri, Geoff","year":2024,"journal":"Pancreas, 53(7), e560-e565","doi":"10.1097/MPA.0000000000002336","pmid":"38986077","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08066","title":"Semaglutide and cardiovascular outcomes in patients with obesity and prevalent heart failure: a prespecified analysis of the SELECT trial.","authors":"Deanfield, John; Verma, Subodh; Scirica, Benjamin M; Kahn, Steven E; Emerson, Scott S; Ryan, Donna; Lingvay, Ildiko; Colhoun, Helen M; Plutzky, Jorge; Kosiborod, Mikhail N; Hovingh, G Kees; Hardt-Lindberg, Søren; Frenkel, Ofir; Weeke, Peter E; Rasmussen, Søren; Goudev, Assen; Lang, Chim C; Urina-Triana, Miguel; Pietilä, Mikko; Lincoff, A Michael","year":2024,"journal":"Lancet (London, England), 404(10454), 773-786","doi":"10.1016/S0140-6736(24)01498-3","pmid":"39181597","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 4,286 patients with heart failure at enrollment (out of 17,604 total), semaglutide 2.4 mg weekly significantly improved all cardiovascular outcomes compared to placebo: MACE HR 0.72 (95% CI 0.60–0.87), composite heart failure endpoint HR 0.79 (0.64–0.98), cardiovascular death HR 0.76 (0.59–0.97), and all-cause death HR 0.81 (0.66–1.00).\n\nBenefits were consistent across heart failure subtypes: HFrEF showed MACE HR 0.65 (0.49–0.87) and HFpEF showed MACE HR 0.69 (0.51–0.91). No significant treatment interaction was observed across age, sex, BMI, NYHA status, or diuretic use subgroups. Serious adverse events were less frequent with semaglutide regardless of heart failure subtype.","whyItMatters":"Heart failure in obese patients is extremely common and difficult to treat, with limited proven therapies especially for HFpEF. This Lancet analysis from one of the largest cardiovascular outcomes trials ever conducted provides strong evidence that semaglutide benefits heart failure patients regardless of subtype — a finding that could change prescribing guidelines and help millions of patients at the intersection of obesity and heart failure.","specificNumbers":"","methodology":"Prespecified subanalysis of the SELECT trial, a randomized, double-blind, multicenter, placebo-controlled, event-driven phase 3 trial conducted across 41 countries. 17,604 adults aged 45+ with BMI ≥27 and established cardiovascular disease were randomized 1:1 to semaglutide 2.4 mg weekly or placebo, titrated over 16 weeks. Patients were subclassified by heart failure status and type (HFpEF, HFrEF, or unclassified). Enrollment ran from October 2018 to March 2021.","limitations":"This is a prespecified subgroup analysis, which carries less statistical power than the primary trial endpoint. Heart failure classification was investigator-defined rather than adjudicated, and 15.5% of heart failure patients were unclassified. The trial was sponsored by Novo Nordisk. Patients with severe heart failure (NYHA Class IV) may have been underrepresented. The trial excluded patients with diabetes, limiting generalizability to the diabetic heart failure population."},{"rthcId":"RPEP-08067","title":"Peptide nanovaccine in melanoma immunotherapy.","authors":"Dehghankhold, Mahvash; Sadat Abolmaali, Samira; Nezafat, Navid; Mohammad Tamaddon, Ali","year":2024,"journal":"International immunopharmacology, 129, 111543","doi":"10.1016/j.intimp.2024.111543","pmid":"38301413","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08068","title":"Long-acting exenatide does not prevent cognitive decline in mild cognitive impairment: a proof-of-concept clinical trial.","authors":"Dei Cas, A; Micheli, M M; Aldigeri, R; Gardini, S; Ferrari-Pellegrini, F; Perini, M; Messa, G; Antonini, M; Spigoni, V; Cinquegrani, G; Vazzana, A; Moretti, V; Caffarra, P; Bonadonna, R C","year":2024,"journal":"Journal of endocrinological investigation, 47(9), 2339-2349","doi":"10.1007/s40618-024-02320-7","pmid":"38565814","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The primary endpoint — change in ADAS-Cog11 cognitive score at 32 weeks — showed no significant difference between exenatide and control groups (p=0.17). A gender interaction was detected (p=0.04), driven by worsening ADAS-Cog11 scores in women randomized to exenatide (p=0.018), even after adjusting for age, education level, dysglycemia, and baseline cognitive scores.\n\nExenatide did demonstrate expected metabolic effects: fasting plasma glucose decreased (p=0.02) and body weight decreased (p=0.03) in the treatment group, confirming GLP-1 receptor engagement. However, these metabolic improvements did not translate into cognitive benefits.","whyItMatters":"There's enormous interest in whether GLP-1 drugs could prevent or treat Alzheimer's disease, fueled by promising animal data and observational studies. This rigorous proof-of-concept trial provides an important reality check: exenatide did not slow cognitive decline in mild cognitive impairment over 32 weeks. The concerning signal in women adds complexity. These results are crucial for tempering premature optimism and guiding the design of future trials with different drugs, doses, or patient populations.","specificNumbers":"","methodology":"Randomized proof-of-concept clinical trial (NCT03881371) with 32 patients (16 female) with mild cognitive impairment. Participants were randomized to slow-release exenatide (2 mg subcutaneous once weekly, n=17) or no treatment (n=15) for 32 weeks. The primary endpoint was change in ADAS-Cog11 score. Secondary endpoints included additional cognitive tests and plasma biomarkers of GLP-1 receptor engagement. Analysis was conducted by intention to treat.","limitations":"Very small sample size (32 patients) severely limits statistical power to detect moderate cognitive effects. The trial used no treatment rather than placebo as the control, which does not account for placebo effects. The 32-week duration may be too short to detect neuroprotective effects in a slowly progressive condition. Exenatide may have limited brain penetration compared to newer GLP-1 drugs. The study focused on mild cognitive impairment broadly, not specifically on Alzheimer's disease pathology."},{"rthcId":"RPEP-08069","title":"Liraglutide enhances insulin secretion and prolongs the remission period in adults with newly diagnosed type 1 diabetes (the NewLira study): A randomized, double-blind, placebo-controlled trial.","authors":"Dejgaard, Thomas F; Frandsen, Christian S; Kielgast, Urd; Størling, Joachim; Overgaard, Anne J; Svane, Maria S; Olsen, Markus Harboe; Thorsteinsson, Birger; Andersen, Henrik U; Krarup, Thure; Holst, Jens J; Madsbad, Sten","year":2024,"journal":"Diabetes, obesity & metabolism, 26(11), 4905-4915","doi":"10.1111/dom.15889","pmid":"39192527","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"After 52 weeks, patients on liraglutide maintained their C-peptide response (a measure of natural insulin production) while placebo patients saw theirs decline significantly (P = .002). The liraglutide group needed less insulin over time — dropping from 0.30 to 0.23 units/kg/day — while the placebo group's needs increased from 0.29 to 0.43 units/kg/day (P < .001).\n\nThirteen liraglutide patients achieved periods without any insulin injections, lasting an average of 22 weeks (range: 3–52 weeks), compared to only two placebo patients who managed an average of 6 weeks insulin-free. However, six weeks after stopping liraglutide, C-peptide levels were similar between groups, indicating the benefit did not persist after discontinuation.","whyItMatters":"Type 1 diabetes is an autoimmune disease that destroys insulin-producing beta cells. There is currently no approved treatment to slow this destruction. This trial shows that a widely available GLP-1 drug can temporarily preserve remaining beta cell function in the critical first year after diagnosis — a 'honeymoon period' when intervention may have the most impact. While the effect didn't last after stopping the drug, it opens the door to combination strategies that might achieve lasting remission.","specificNumbers":"","methodology":"This was a multicenter, double-blind, parallel-group, randomized controlled trial. Sixty-eight adults newly diagnosed with type 1 diabetes who still had measurable insulin production (stimulated C-peptide > 0.2 nmol/L) were randomly assigned 1:1 to receive either 1.8 mg liraglutide or placebo daily for 52 weeks, followed by 6 weeks of observation on insulin alone. Beta cell function was assessed using C-peptide area under the curve from a 4-hour liquid mixed-meal test.","limitations":"The sample size of 68 patients was relatively small for detecting durable clinical effects. The protective effect on beta cells did not persist after liraglutide was stopped, raising questions about whether continuous treatment would be practical. The study only followed patients for 58 weeks total, so long-term outcomes remain unknown. Gastrointestinal side effects, though transient, were common with liraglutide."},{"rthcId":"RPEP-08070","title":"GLP-1 Receptor Agonist Treatment Improves Fasting and Postprandial Lipidomic Profiles Independently of Diabetes and Weight Loss.","authors":"Della Pepa, Giuseppe; Patrício, Bárbara G; Carli, Fabrizia; Sabatini, Silvia; Astiarraga, Brenno; Ferrannini, Ele; Camastra, Stefania; Gastaldelli, Amalia","year":2024,"journal":"Diabetes, 73(10), 1605-1614","doi":"10.2337/db23-0972","pmid":"38976482","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 30 severely obese non-diabetic adults (15 exenatide, 15 diet-only control) over 3 months:\n\nFasting improvements with exenatide:\n- Reduced ceramides (CERs) and lysophosphatidylcholines (LPCs) linked to cardiometabolic risk\n- Relatively increased unsaturated phospholipid species (PC, LPC) with protective cardiovascular effects\n- Total lipid species concentrations unchanged — the composition shifted beneficially\n\nPostprandial improvements:\n- Significantly lowered postprandial triglycerol (TAG) concentrations, particularly saturated TAGs with 44-54 carbons\n- Reduced free fatty acid clearance\n- Reduced postprandial ceramides and lipid species linked to cardiometabolic risk\n\nAll changes remained statistically significant after adjusting for weight loss (-5.5% vs -1.9%, P = 0.052), demonstrating weight loss-independent effects.","whyItMatters":"The question of whether GLP-1 drugs improve cardiovascular risk through weight loss alone or through direct metabolic effects has major implications. If benefits are just from weight loss, any weight loss method would work equally. This study shows exenatide directly improves the lipid species most strongly associated with heart disease risk — ceramides and saturated triglycerides — independent of weight loss. This helps explain the cardiovascular benefits seen in GLP-1RA clinical trials and suggests these drugs have intrinsic cardioprotective properties.","specificNumbers":"","methodology":"Controlled clinical study with 30 severely obese non-diabetic individuals (26 female, 4 male, BMI >40, HbA1c 5.76%) assigned 1:1 to diet plus exenatide (10 μg twice daily) or diet alone for 3 months. Comprehensive lipidomic profiling was performed using LC-QTOF mass spectrometry before and after treatment, both fasting and during a 6-hour mixed-meal tolerance test with isotope tracer study. Fatty acid composition was measured by GC-MS. Statistical adjustments for weight loss were applied.","limitations":"Small sample size (15 per group) limits statistical power and generalizability. The study was not blinded or placebo-controlled. The population was predominantly female (26/30) and severely obese (BMI >40), limiting applicability to other demographics. Only exenatide was tested; results may not apply to all GLP-1RAs. The 3-month duration captures early changes but not long-term effects. The weight loss difference (-5.5% vs -1.9%) trended toward significance and may have contributed to some changes despite statistical adjustment."},{"rthcId":"RPEP-08071","title":"The Efficacy and Safety of CollaSel Pro® Hydrolyzed Collagen Peptide Supplementation without Addons in Improving Skin Health in Adult Females: A Double Blind, Randomized, Placebo-Controlled Clinical Study Using Biophysical and Skin Imaging Techniques.","authors":"Demir-Dora, Devrim; Ozsoy, Umut; Yildirim, Yilmaz; Yilmaz, Oguz; Aytac, Peri; Yilmaz, Beste; Dogan Kurtoglu, Emel; Akman, Ayse; Tezman, Selim; Inaloz, Huseyin Serhat; Erenmemisoglu, Aydin","year":2024,"journal":"Journal of clinical medicine, 13(18)","doi":"10.3390/jcm13185370","pmid":"39336856","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08072","title":"Safety and efficacy of GLP-1 and glucagon receptor dual agonist for the treatment of type 2 diabetes and obesity: a systematic review and meta-analysis of randomized controlled trials.","authors":"Deng, Bixin; Ruan, Tiechao; Lu, Wenting; Ying, Junjie; Li, Shiping; Zhou, Ruixi; Mu, Dezhi","year":2024,"journal":"Endocrine, 86(1), 15-27","doi":"10.1007/s12020-024-03857-6","pmid":"38740695","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08073","title":"Engineering a wolf spider A-family toxin towards increased antimicrobial activity but low toxicity.","authors":"Dersch, Ludwig; Stahlhut, Antonia; Eichberg, Johanna; Paas, Anne; Hardes, Kornelia; Vilcinskas, Andreas; Lüddecke, Tim","year":2024,"journal":"Toxicon : official journal of the International Society on Toxinology, 247, 107810","doi":"10.1016/j.toxicon.2024.107810","pmid":"38880255","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08074","title":"Exploring the modulatory effects of sotagliflozin on dyslipidemia in mice: The role of glucagon, fibroblast growth factor 21 and glucagon-like peptide 1.","authors":"Deshmukh, Nitin J; Kalshetti, M S; Patil, Mohan; Autade, Pankaj; Sangle, Ganesh V","year":2024,"journal":"Clinical and experimental pharmacology & physiology, 51(5), e13854","doi":"10.1111/1440-1681.13854","pmid":"38527859","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08075","title":"Vital Exhaustion and Biomarkers Associated With Cardiovascular Risk: The ARIC Study.","authors":"Deshotels, Matthew R; Al Rifai, Mahmoud; Sun, Caroline; Agha, Ali; Selvin, Elizabeth; Windham, B Gwen; Vaccarino, Viola; Michos, Erin D; Jneid, Hani; Levine, Glenn N; Fagundes, Christopher; Virani, Salim S; Ballantyne, Christie M; Nambi, Vijay","year":2024,"journal":"JACC. Advances, 3(11), 101355","doi":"10.1016/j.jacadv.2024.101355","pmid":"39539949","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08076","title":"Management and Amelioration of Knee Joint Osteoarthritis in Adults Using a Novel High-Functional Bovine Collagen Peptide as a Nutritional Therapy: A Double-Blind, Prospective, Multicentric, Randomized, Active and Placebo Controlled, Five-Arm, Clinical Study to Evaluate the Efficacy, Safety, and Tolerability.","authors":"Devasia, Sheena; Joseph, Jinu T; P S, Stephena; Koizumi, Seiko; Clarke, Liz; V T, Sriraam; Kailas, Abhilash Parameswaran; Madhavan, Shajil","year":2024,"journal":"Cartilage, 15(4), 363-374","doi":"10.1177/19476035231221211","pmid":"38235711","tags":[],"studyType":"randomized-controlled-trial","evidenceStrength":"moderate","keyFinding":"A novel 'high-functional' bovine collagen peptide (Type J) significantly improved knee osteoarthritis symptoms at all tested doses (2.5g, 5g, and 10g daily) over 90 days. The most striking finding was that just 2.5g of the Type J collagen peptide performed equivalently to 10g of conventional collagen peptides across multiple outcome measures including pain, joint function, quality of life, cartilage degradation biomarkers (CTX-II), and MRI-based structural assessment (MOAKS).\n\nAll collagen peptide groups — both Type J and conventional — outperformed placebo, confirming that collagen peptide supplementation provides real benefit for knee osteoarthritis beyond placebo effect.","whyItMatters":"Collagen peptide supplements are widely used for joint health, but questions about optimal dosing and whether newer formulations truly offer advantages over conventional products are important for consumers and clinicians. This study demonstrates that peptide engineering can produce collagen fragments that are 4 times more potent than conventional collagen — meaning people could take much smaller doses and get the same benefit. It also provides rigorous evidence (double-blind, placebo-controlled, with MRI imaging) that collagen peptides genuinely improve osteoarthritis beyond just pain relief.","specificNumbers":"n=100 · 5 arms · 90 days · Type J 2.5g = conventional 10g in efficacy · improved WOMAC, QoL, CTX-II, MOAKS · doses: 2.5g, 5g, 10g Type J vs 10g conventional vs placebo","methodology":"This was a double-blind, prospective, multicentric, randomized, five-arm clinical trial with 100 adults with knee osteoarthritis. Participants received either 2.5g, 5g, or 10g of high-functional Type J bovine collagen peptides, 10g of conventional collagen peptides, or 10g of placebo daily for 90 days. Outcomes included the WOMAC arthritis score, pain assessment, quality of life, physician's impression of change, serum CTX-II (a biomarker of cartilage breakdown), and MRI-based MOAKS knee scoring.","limitations":"The sample size of 100 participants split across 5 groups means only about 20 people per arm, which is relatively small for detecting dose-response differences. The 90-day duration may not capture long-term effects or structural changes that take longer to develop. The study was funded by the manufacturer of the Type J collagen product, which should be considered when interpreting results."},{"rthcId":"RPEP-08077","title":"Silver and Copper Nanoparticle-Loaded Self-Assembled Pseudo-Peptide Thiourea-Based Organic-Inorganic Hybrid Gel with Antibacterial and Superhydrophobic Properties for Antifouling Surfaces.","authors":"Devi, Renu; Singh, Gagandeep; Singh, Anoop; Singh, Jagdish; Kaur, Navneet; Singh, Narinder","year":2024,"journal":"ACS applied bio materials, 7(6), 4162-4174","doi":"10.1021/acsabm.4c00476","pmid":"38769764","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08078","title":"Glucagon-like peptide-1 receptor agonists reverse nerve morphological abnormalities in diabetic peripheral neuropathy.","authors":"Dhanapalaratnam, Roshan; Issar, Tushar; Lee, Alexandra T K; Poynten, Ann M; Milner, Kerry-Lee; Kwai, Natalie C G; Krishnan, Arun V","year":2024,"journal":"Diabetologia, 67(3), 561-566","doi":"10.1007/s00125-023-06072-6","pmid":"38189936","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08079","title":"Functional attributes of bioactive peptides of bovine milk origin and application of in silico approaches for peptide prediction and functional annotations.","authors":"Dhar, Hena; Verma, Subhash; Dogra, Sarita; Katoch, Shailja; Vij, Rishika; Singh, Geetanjali; Sharma, Mandeep","year":2024,"journal":"Critical reviews in food science and nutrition, 64(26), 9432-9454","doi":"10.1080/10408398.2023.2212803","pmid":"37218679","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08080","title":"A retrospective observational clinical study of triple negative breast cancer cases treated with Di Bella Method: A preliminary data.","authors":"Di Bella, Giuseppe; Moscato, Ilaria; Costanzo, Elena; Di Giorgi, Giovanni","year":2024,"journal":"Neuro endocrinology letters, 45(7-8), 510-522","doi":null,"pmid":"39737501","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08081","title":"Peptide receptor radionuclide therapy combinations for neuroendocrine tumours in ongoing clinical trials: status 2023.","authors":"di Santo, Gianpaolo; Santo, Giulia; Sviridenko, Anna; Virgolini, Irene","year":2024,"journal":"Theranostics, 14(3), 940-953","doi":"10.7150/thno.91268","pmid":"38250038","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08082","title":"Assessing the occurrence of hypertension in patients receiving calcitonin gene-related peptide monoclonal antibodies for episodic and chronic migraine: a systematic review and meta-analysis.","authors":"Di, Meiqi; Hu, Lingling; Gui, Shuhua; Li, Chaosheng; Han, Likun","year":2024,"journal":"Journal of oral & facial pain and headache, 38(4), 24-32","doi":"10.22514/jofph.2024.036","pmid":"39800953","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08083","title":"Lung antimicrobial proteins and peptides: from host defense to therapeutic strategies.","authors":"Di, Yuanpu Peter; Kuhn, Jenna Marie; Mangoni, Maria Luisa","year":2024,"journal":"Physiological reviews, 104(4), 1643-1677","doi":"10.1152/physrev.00039.2023","pmid":"39052018","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08084","title":"Subcutaneous Semaglutide during Breastfeeding: Infant Safety Regarding Drug Transfer into Human Milk.","authors":"Diab, Hanin; Fuquay, Taylor; Datta, Palika; Bickel, Ulrich; Thompson, Jonathan; Krutsch, Kaytlin","year":2024,"journal":"Nutrients, 16(17)","doi":"10.3390/nu16172886","pmid":"39275201","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08085","title":"Collagen peptides affect collagen synthesis and the expression of collagen, elastin, and versican genes in cultured human dermal fibroblasts.","authors":"Dierckx, Stephan; Patrizi, Milagros; Merino, Marián; González, Sonia; Mullor, José L; Nergiz-Unal, Reyhan","year":2024,"journal":"Frontiers in medicine, 11, 1397517","doi":"10.3389/fmed.2024.1397517","pmid":"38751975","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08086","title":"Evaluation of potential antiviral activities of antimicrobial peptides in fish mucus.","authors":"Dik, Irmak; Dik, Burak; Tufan, Öznur; Er, Ayşe","year":2024,"journal":"Fundamental & clinical pharmacology, 38(4), 695-702","doi":"10.1111/fcp.12996","pmid":"38378226","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Skin mucus from three fish species showed antiviral activity against herpes simplex virus type 1 (HSV-1), with sea bream and rainbow trout mucus demonstrating higher activity (2-4 and 2-5 inhibition, respectively) than sea bass (2-2). The higher antiviral activity correlated with higher levels of antimicrobial peptides — cathelicidin, hepcidin, galectin 2, and C10ORF99 — in the mucus of the more effective species.\n\nThe association between AMP levels and antiviral potency suggests these peptides contribute directly to the antiviral defense of fish skin mucus, pointing to their potential as novel antiviral agents or supplements.","whyItMatters":"While antimicrobial peptides are well-studied for their antibacterial properties, antiviral activity — especially against human viruses like HSV-1 — is less explored. Finding that fish skin mucus peptides can inhibit a common human virus opens a new source for antiviral drug discovery. Fish produce AMPs in abundance as their first-line defense, and these peptides have been refined by evolution to work in the challenging aquatic environment.","specificNumbers":"3 fish species tested · HSV-1 inhibition: sea bream 2-4, rainbow trout 2-5, sea bass 2-2 · 4 AMPs measured (cathelicidin, hepcidin, galectin 2, C10ORF99) · Higher AMPs = higher antiviral activity","methodology":"Skin mucus was collected from sea bream, rainbow trout, and sea bass. Antiviral activity against HSV-1 was evaluated using standard viral inhibition assays. Levels of four antimicrobial peptides (cathelicidin, hepcidin, galectin 2, C10ORF99), superoxide dismutase (SOD), catalase (CAT), and immunoglobulin M were measured in the mucus. Correlations between AMP levels and antiviral activity were assessed.","limitations":"The study measured antiviral activity of crude mucus rather than purified individual peptides, making it impossible to determine which specific AMP is responsible for the antiviral effect. The antiviral activity was only tested against HSV-1 — activity against other viruses is unknown. The inhibition titers (2-2 to 2-5) are relatively modest. No mechanism of antiviral action was elucidated. The leap from fish mucus to human therapeutic application requires extensive development."},{"rthcId":"RPEP-08087","title":"Treatment of Hypothalamic Obesity With GLP-1 Analogs.","authors":"Dimitri, Paul; Roth, Christian L","year":2024,"journal":"Journal of the Endocrine Society, 9(1), bvae200","doi":"10.1210/jendso/bvae200","pmid":"39703362","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08088","title":"Comprehensive Review of the Safety and Efficacy of Thymosin Alpha 1 in Human Clinical Trials.","authors":"Dinetz, Elliot; Lee, Edwin","year":2024,"journal":"Alternative therapies in health and medicine, 30(1), 6-12","doi":null,"pmid":"38308608","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across more than 30 clinical trials involving over 11,000 human subjects worldwide, thymosin alpha-1 demonstrated consistent safety and efficacy as an immune modulator. The peptide showed significant effectiveness in treating COVID-19 (improving immune function in severe cases), autoimmune conditions (restoring immune balance), and cancer (enhancing immune-mediated anti-tumor responses). No patterns of serious safety concerns emerged across the reviewed trials. The authors conclude the FDA's 2023 restriction on compounding pharmacies producing Tα1 is not supported by the clinical evidence base.","whyItMatters":"Thymosin alpha-1 is one of the most extensively studied therapeutic peptides, with a long history of clinical use in over 30 countries (primarily as Zadaxin). The 2023 FDA restriction on compounding pharmacies producing Tα1 and other peptides generated significant controversy. This review compiles the clinical evidence to argue for continued access, directly addressing a major regulatory debate in the peptide therapeutics space.","specificNumbers":"","methodology":"Narrative review with systematic search of PubMed, Google Scholar, and Cochrane Library for clinical trials involving thymosin alpha-1 in COVID-19, infectious diseases, cancer, and autoimmune diseases. The review analyzed outcomes from over 11,000 human subjects across more than 30 trials conducted worldwide.","limitations":"The review is described as a narrative review rather than a systematic review with strict inclusion criteria, which introduces potential selection bias. The authors advocate strongly for Tα1 availability, which may affect objectivity. Many of the included trials were conducted in countries with different regulatory standards. Publication bias — where positive results are more likely to be published — is a concern. The quality and design of the individual trials varies significantly."},{"rthcId":"RPEP-08089","title":"Design of Auto-Adaptive Drug Delivery System for Effective Delivery of Peptide Drugs to Overcoming Mucus and Epithelial Barriers.","authors":"Ding, Ruihuan; Li, Yanping; Zheng, Wei; Sun, Yiying; Zhao, Zhenyu; Zhang, Houqian; Yuan, Ranran; Wang, Aiping; Sun, Kaoxiang; Wang, Hongbo; Shi, Yanan","year":2024,"journal":"The AAPS journal, 26(5), 102","doi":"10.1208/s12248-024-00971-1","pmid":"39266802","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The Pc-AT-CLs (protein corona-AT 1002-cationic liposomes) system demonstrated a two-stage adaptive delivery mechanism for oral liraglutide:\n\n- Stage 1 (mucus penetration): BSA protein corona provided a hydrophilic, electrically neutral surface that reduced mucus adherence. Mucus penetration was 1.45 times greater than uncoated AT-CLs.\n- Stage 2 (epithelial transport): After penetrating the mucus layer, the protein corona fell off, exposing the AT 1002 peptide and cationic surface. The apparent permeability coefficient (Papp) of AT-CLs was 2.03 times that of unmodified cationic liposomes.\n\nIn vivo testing showed significant hypoglycemic (blood sugar-lowering) effects and enhanced relative bioavailability compared to free liraglutide, confirming that the system protected liraglutide from degradation and improved its oral absorption.","whyItMatters":"Converting injectable peptide drugs like liraglutide into oral medications is one of the biggest challenges in drug delivery. While oral semaglutide exists, it requires specific fasting conditions and has limited bioavailability. This auto-adaptive system addresses the two main barriers to oral peptide delivery — mucus and epithelial cells — in sequence, using a single smart nanoparticle that adapts to each environment. If perfected, this approach could make oral delivery feasible for many peptide drugs currently requiring injection.","specificNumbers":"","methodology":"Researchers constructed cationic liposomes loaded with liraglutide, functionalized with AT 1002 (a tight junction-opening peptide), and coated with a BSA protein corona. Transmucus transport was tested using mucus barrier models. Transmembrane transport was assessed using intestinal cell permeability assays measuring apparent permeability coefficients. In vivo testing in rats evaluated hypoglycemic effects and oral bioavailability of the complete Pc-AT-CLs system compared to free liraglutide.","limitations":"The study was conducted in rats, whose gut physiology differs from humans in mucus composition, transit time, and barrier thickness. Specific bioavailability percentages and dose comparisons are not detailed in the abstract. The BSA protein corona may trigger immune responses in humans. Manufacturing scalability and stability of the multi-component system were not addressed. The long-term safety of AT 1002 (which opens tight junctions between cells) is a concern, as this could potentially allow passage of unwanted substances. Comparison to the existing oral semaglutide formulation was not included."},{"rthcId":"RPEP-08090","title":"Potent and Protease Resistant Azapeptide Agonists of the GLP-1 and GIP Receptors.","authors":"Dinsmore, Tristan C; Liu, Jamie; Miao, Jiayuan; Ünsal, Özge; Sürmeli, Damla; Beinborn, Martin; Lin, Yu-Shan; Kumar, Krishna","year":2024,"journal":"Angewandte Chemie (International ed. in English), 63(49), e202410237","doi":"10.1002/anie.202410237","pmid":"39151024","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A single aza-amino acid substitution (carbon → nitrogen) at the second position from the N-terminus made GLP-1 and GIP peptide agonists completely resistant to DPP4 degradation while retaining full potency and efficacy at their respective receptors (GLP-1R and GIPR).\n\nMolecular dynamics simulations confirmed that aza-amino acids can adopt the same conformational space as natural amino acids when the peptide binds its receptor. The modification was successfully applied to semaglutide and a dual GLP-1R/GIPR agonist, demonstrating it works as a viable alternative to existing DPP4 resistance strategies and offers additional structural variation that may influence downstream signaling.","whyItMatters":"Current GLP-1 drugs like semaglutide require complex chemical modifications (fatty acid chains, amino acid substitutions) to resist DPP4 breakdown. This study shows that a single atom swap achieves the same protection with minimal disruption to the peptide's natural structure. This approach could simplify the design of next-generation peptide drugs and may create new opportunities for fine-tuning their pharmacological properties.","specificNumbers":"","methodology":"The researchers synthesized GLP-1 and GIP peptide analogs incorporating aza-amino acids — bioisosteric replacements where backbone carbon is swapped for nitrogen. They tested DPP4 resistance in enzyme assays, measured receptor activation potency and efficacy, and used molecular dynamics simulations to understand how the structural modification affects peptide conformation and receptor binding.","limitations":"This is a medicinal chemistry and in vitro study — no animal or human pharmacokinetic data are presented. While the modified peptides retained receptor potency, their actual in vivo stability, bioavailability, and therapeutic efficacy need to be demonstrated. The impact of the aza-amino acid modification on downstream signaling pathways beyond receptor activation is noted as a possibility but not fully characterized."},{"rthcId":"RPEP-08091","title":"The oral intake of specific Bioactive Collagen Peptides (BCP) improves gait and quality of life in canine osteoarthritis patients-A translational large animal model for a nutritional therapy option.","authors":"Dobenecker, Britta; Böswald, Linda Franziska; Reese, Sven; Steigmeier-Raith, Stephanie; Trillig, Lukas; Oesser, Steffen; Schunck, Michael; Meyer-Lindenberg, Andrea; Hugenberg, Jutta","year":2024,"journal":"PloS one, 19(9), e0308378","doi":"10.1371/journal.pone.0308378","pmid":"39298537","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08092","title":"In silico Identification of MHC Displayed Tumor Associated Peptides in Ovarian Cancer for Multi-Epitope Vaccine Construct.","authors":"Dobhal, Shivashish; Chauhan, Kanchan; Kumar, Sachin; Shikha, Sristy; Jogi, Mukesh K; Kumar, Dinesh; Kumar, Anuj; Jaiswal, Varun K; Kumar, Pramod","year":2024,"journal":"Endocrine, metabolic & immune disorders drug targets, 24(12), 1401-1413","doi":"10.2174/0118715303169428231205173914","pmid":"38275062","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08093","title":"A cost comparison of GLP-1 receptor agonists and bariatric surgery: what is the break even point?","authors":"Docimo, Salvatore; Shah, Jay; Warren, Gus; Ganam, Samer; Sujka, Joseph; DuCoin, Christopher","year":2024,"journal":"Surgical endoscopy, 38(11), 6560-6565","doi":"10.1007/s00464-024-11191-1","pmid":"39285034","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Using 2023 national retail prices for GLP-1 receptor agonists compared to inflation-adjusted 2015 surgical costs, the cumulative medication costs surpassed surgery costs relatively quickly:\n- Saxenda and Wegovy exceeded the cost of sleeve gastrectomy within approximately 9 months\n- Saxenda and Wegovy exceeded the cost of Roux-en-Y gastric bypass in less than 1 year\n- Byetta (the most affordable GLP-1 RA) became costlier than either surgery after approximately 1.5 years\n\nGLP-1 drugs also take time to reach full effectiveness, delaying weight loss while costs accumulate, and weight typically returns after discontinuation.","whyItMatters":"As GLP-1 peptide drugs generate global spending measured in tens of billions of dollars annually, the question of cost-effectiveness compared to existing surgical alternatives is critical for patients, insurers, and health policy. This study reveals that what appears to be a less invasive option (medication over surgery) is actually more expensive within months — not years — of starting treatment. For healthcare systems struggling with obesity costs, this has major implications for coverage decisions and treatment guidelines.","specificNumbers":"","methodology":"Cost comparison study using average 2023 US national retail prices for GLP-1 receptor agonists and 2015 surgical cost estimates adjusted for inflation. Cumulative medication costs were plotted over time against the one-time flat cost of sleeve gastrectomy and Roux-en-Y gastric bypass. Break-even points were calculated as the time when ongoing medication costs equal the surgical cost.","limitations":"The study used national retail prices, which may differ significantly from actual out-of-pocket costs for patients with insurance coverage. Long-term costs associated with surgical complications, follow-up care, or medical management of comorbidities were not fully evaluated for either modality. Patient preferences, quality of life, and clinical outcomes (weight loss magnitude, comorbidity resolution) were not compared. Insurance coverage, patient assistance programs, and forthcoming generic/biosimilar pricing could significantly change the cost calculus. The surgical cost estimates were from 2015 (inflation-adjusted), which may not reflect current pricing."},{"rthcId":"RPEP-08094","title":"NPY-mediated synaptic plasticity in the extended amygdala prioritizes feeding during starvation.","authors":"Dodt, Stephan; Widdershooven, Noah V; Dreisow, Marie-Luise; Weiher, Lisa; Steuernagel, Lukas; Wunderlich, F Thomas; Brüning, Jens C; Fenselau, Henning","year":2024,"journal":"Nature communications, 15(1), 5439","doi":"10.1038/s41467-024-49766-0","pmid":"38937485","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08095","title":"FDG-PET/CT-based respiration-gated lung segmentation and quantification of lung inflammation in COPD patients.","authors":"Dogan, Ayse Dudu Altintas; Christensen, Thomas Quist; Jensen, Torben Tranborg; Juhl, Claus Bogh; Hilberg, Ole; Bladbjerg, Else-Marie; Hess, Søren","year":2024,"journal":"BMC research notes, 17(1), 170","doi":"10.1186/s13104-024-06820-w","pmid":"38902794","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08096","title":"The LUSBI Protocol (Lung Ultrasound/BREST Score/Inferior Vena Cava)-Its Role in a Differential Diagnostic Approach to Dyspnea of Cardiogenic and Non-Cardiogenic Origin.","authors":"Dojcinovic, Boris; Banjac, Nada; Vukmirovic, Sasa; Dojcinovic, Tamara; Vasovic, Lucija V; Mihajlovic, Dalibor; Vasovic, Velibor","year":2024,"journal":"Medicina (Kaunas, Lithuania), 60(9)","doi":"10.3390/medicina60091521","pmid":"39336562","tags":["natriuretic-peptides","diagnostics"],"studyType":"clinical-study","evidenceStrength":"low-moderate","keyFinding":"Researchers created the LUSBI protocol — combining lung ultrasound, BREST heart failure risk scores, and inferior vena cava measurements — to distinguish cardiac from non-cardiac causes of shortness of breath in the emergency department. The protocol was validated against NT-proBNP, a peptide biomarker for heart failure.\n\nNT-proBNP values differed significantly across LUSBI protocol profiles (p=0.004), confirming that the protocol's ultrasound-based classifications align with biochemical evidence of heart failure. There was also a significant difference (p=0.001) in LUSBI profiles between patients categorized by central venous pressure.\n\nThe protocol proved effective for quickly confirming or ruling out a cardiac cause of breathing difficulty in 80 emergency department patients.","whyItMatters":"Shortness of breath is one of the most common emergency department complaints, and quickly determining whether it's caused by heart failure or lung disease changes treatment entirely. The LUSBI protocol offers a rapid bedside approach using ultrasound that was validated against the gold-standard peptide biomarker NT-proBNP. This is relevant to peptide science because NT-proBNP — a fragment of brain natriuretic peptide — serves as the laboratory benchmark against which new diagnostic approaches are measured.","specificNumbers":"n=80 · p=0.004 for NT-proBNP across LUSBI profiles · p=0.001 for CVP category differences · 2 groups: experimental (dyspneic) and control","methodology":"Cross-sectional study in an emergency department. 80 patients divided into experimental (dyspnea as main complaint) and control groups. Each patient received lung ultrasound, inferior vena cava measurements, and BREST scoring to create LUSBI protocol profiles. NT-proBNP blood levels served as the biochemical reference standard for cardiac origin.","limitations":"Small sample size (80 patients) from a single emergency department. Cross-sectional design cannot establish the protocol's predictive accuracy over time. No comparison with established diagnostic algorithms like the Framingham criteria. The study was conducted at one center, limiting generalizability."},{"rthcId":"RPEP-08097","title":"Cardio-Renal-Metabolic Outcomes Associated With the Use of GLP-1 Receptor Agonists After Heart Transplantation.","authors":"Donald, Elena M; Driggin, Elissa; Choe, Jason; Batra, Jaya; Vargas, Fabian; Lindekens, Jordan; Fried, Justin A; Raikhelkar, Jayant K; Bae, David J; Oh, Kyung T; Yuzefpolskaya, Melana; Colombo, Paolo C; Latif, Farhana; Sayer, Gabriel; Uriel, Nir; Clerkin, Kevin J; DeFilippis, Ersilia M","year":2024,"journal":"Clinical transplantation, 38(7), e15401","doi":"10.1111/ctr.15401","pmid":"39023081","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Over a median follow-up of 383 days, 74 heart transplant recipients on GLP-1 receptor agonists showed significant improvements: mean BMI decreased from 33.3 to 31.5 kg/m² (p < 0.0001), HbA1c from 7.3% to 6.7% (p = 0.005), LDL cholesterol from 78.6 to 70.3 mg/dL (p = 0.018), and basal insulin daily dose from 32.6 to 24.8 units (p = 0.0002).\n\nThe majority (76%) received semaglutide. Primary indications were T2DM alone (45%) or combined T2DM and obesity (35%). The drugs were well tolerated and rarely required adjustments to immunosuppression dosing — a critical safety consideration in transplant patients.","whyItMatters":"Heart transplant recipients have high rates of metabolic complications — diabetes, obesity, and high cholesterol — largely driven by their immunosuppressive medications. Yet there has been limited evidence on whether GLP-1 drugs are safe to use alongside anti-rejection drugs. This study provides real-world evidence that these peptide therapies are both effective and well tolerated in this vulnerable population, potentially improving long-term transplant outcomes by addressing major cardiovascular risk factors.","specificNumbers":"","methodology":"Retrospective review of all adult heart transplant recipients at a large-volume transplant center who received GLP-1 receptor agonists for at least 1 month post-transplant. Cardiometabolic parameters (BMI, HbA1c, lipid panel, eGFR, NT-proBNP) were compared before drug initiation and at most recent follow-up. Changes in immunosuppression dosing and adverse effects leading to discontinuation were also evaluated.","limitations":"This is a retrospective, single-center study without a control group, making it impossible to separate GLP-1 effects from other concurrent lifestyle or medication changes. The cohort was moderately sized (n=74) and may not represent all transplant populations. Long-term outcomes beyond the study period, including effects on graft survival and rejection rates, were not assessed. Drug-drug interactions with immunosuppressants were monitored but not comprehensively characterized."},{"rthcId":"RPEP-08098","title":"Curcumin inhibits the neuroimmune response mediated by mast cells after pulpitis.","authors":"Dong, Ming; Tang, Jing; Li, Lu-Jia; Dai, Ting; Zuo, Yi-Yan; Jin, Hai-Wei","year":2024,"journal":"Journal of applied oral science : revista FOB, 32, e20230456","doi":"10.1590/1678-7757-2023-0456","pmid":"40531313","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Pulpitis induced significant increases in CGRP-positive neurons and GFAP-positive satellite glial cells (SGCs) in the trigeminal ganglia, along with massive mast cell degranulation. Degranulated mast cells were scattered among CGRP-positive nerve fibers and tryptase-positive mast cells surrounded neurons.\n\nCurcumin treatment: significantly decreased TNF-α, reduced mast cell degranulation, downregulated CGRP expression, decreased TLR4-positive neurons, reduced activated SGCs, lowered PAR2-positive neurons, decreased tryptase expression, and attenuated osteoclast activation in the apical periodontium. This demonstrates that curcumin can suppress the mast cell-CGRP neuroimmune axis in dental inflammation.","whyItMatters":"Dental pain from pulpitis involves CGRP-mediated neuroinflammation in the trigeminal system — the same neuropeptide pathway targeted by migraine drugs. Understanding how mast cells interact with CGRP neurons in dental inflammation could lead to new pain management strategies, and the finding that curcumin can modulate this pathway provides a natural anti-inflammatory approach.","specificNumbers":"","methodology":"Pulpitis was induced in Sprague-Dawley rats. Immunohistochemistry and toluidine blue staining assessed mast cell dynamics, tryptase expression, PAR2, and CGRP levels in the trigeminal ganglia over time. Curcumin was administered by intraperitoneal injection, and its effects on TLR4, CGRP, GFAP, CX3CL1, TNF-α, and other inflammatory markers were measured in the trigeminal ganglia.","limitations":"The study was conducted in rats, and the pulpitis model may not fully replicate human dental inflammation. Curcumin was administered intraperitoneally, not orally or locally, so clinical relevance of the delivery route is uncertain. Curcumin has poor oral bioavailability in humans, which limits direct translation. Specific quantitative comparisons and dose-response data were not detailed in the abstract."},{"rthcId":"RPEP-08099","title":"Effect of Peptide-Polymer Host-Guest Electrostatic Interactions on Self-Assembling Peptide Hydrogels Structural and Mechanical Properties and Polymer Diffusivity.","authors":"Dong, Siyuan; Chapman, Sam L; Pluen, Alain; Richardson, Stephen M; Miller, Aline F; Saiani, Alberto","year":2024,"journal":"Biomacromolecules, 25(6), 3628-3641","doi":"10.1021/acs.biomac.4c00232","pmid":"38771115","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The two novel peptides, E(FKFE)2 and K(FEFK)2, formed transparent hydrogels at pH 7 through physical self-assembly without chemical cross-linking. The charge state of the peptides directly controlled whether samples formed solutions, gels, or precipitates.\n\nWhen loaded with oppositely charged polymers, the hydrogel network changed fundamentally: individual fibrils became smaller, but fiber bundling and aggregation increased, creating denser cross-links. This translated to stiffer, more stable gels that resisted swelling in excess media. Polymer diffusion out of the gel was controlled by electrostatic interactions — oppositely charged polymers diffused more slowly, enabling tunable sustained release. The gels supported 3D culture of 3T3 fibroblasts and human mesenchymal stem cells.","whyItMatters":"Peptide hydrogels are increasingly important for tissue engineering and drug delivery because they're made from amino acids (inherently biocompatible) and self-assemble without toxic chemicals. The ability to tune mechanical properties and release rates simply by choosing the right polymer additive makes these gels much more versatile than previous designs. This is especially valuable for delivering large biological molecules like proteins or growth factors, which are difficult to release in a controlled manner.","specificNumbers":"","methodology":"Researchers synthesized two peptides and characterized their phase behavior across different pH and concentration conditions. Hydrogel structure was analyzed using scattering and microscopy techniques. Mechanical properties were measured by rheology. Cytocompatibility was tested with 3T3 fibroblasts and human mesenchymal stem cells in 3D culture. Polymer loading experiments used poly-L-lysine and dextran at various concentrations, with diffusion measured to assess release kinetics.","limitations":"This is a materials science study with in vitro cell compatibility data only — no animal testing or therapeutic application was demonstrated. The two polymers tested (poly-L-lysine and dextran) are model compounds, not therapeutic molecules, so the release kinetics may differ with actual drug payloads. Long-term stability and degradation of the hydrogels were not assessed. The mechanical properties, while tunable, may not match the requirements of all target tissues."},{"rthcId":"RPEP-08100","title":"Pulmonary aspiration during upper endoscopy in a patient prescribed semaglutide.","authors":"Dong, Tao; Wang, Lan; Wang, Hanying; Xiao, Jun","year":2024,"journal":"Revista espanola de enfermedades digestivas","doi":"10.17235/reed.2024.10844/2024","pmid":"39421913","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08101","title":"A novel angiotensin-converting enzyme (ACE) inhibitory peptide from tilapia skin: Preparation, identification and its potential antihypertensive mechanism.","authors":"Dong, Ye; Yan, Wen; Zhang, Yi-Qi; Dai, Zhi-Yuan","year":2024,"journal":"Food chemistry, 430, 137074","doi":"10.1016/j.foodchem.2023.137074","pmid":"37549627","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08102","title":"Innovative peptide architectures: advancements in foldamers and stapled peptides for drug discovery.","authors":"Dongrui, Zhou; Miyamoto, Maho; Yokoo, Hidetomo; Demizu, Yosuke","year":2024,"journal":"Expert opinion on drug discovery, 19(6), 699-723","doi":"10.1080/17460441.2024.2350568","pmid":"38753534","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08103","title":"Vasoactive Intestinal Peptide-Producing Neuroblastic Tumors: A Rare Cause of Refractory Diarrhea.","authors":"Dornelles Penteado Pacheco E Silva, Luiza; Monteiro Caran, Eliana M","year":2024,"journal":"Cureus, 16(8), e67861","doi":"10.7759/cureus.67861","pmid":"39328672","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08104","title":"Recombinant and Synthetic Affibodies Function Comparably for Modulating Protein Release.","authors":"Dorogin, Jonathan; Benz, Morrhyssey A; Moore, Cameron J; Benoit, Danielle S W; Hettiaratchi, Marian H","year":2024,"journal":"Cellular and molecular bioengineering, 17(4), 305-312","doi":"10.1007/s12195-024-00815-0","pmid":"39372554","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08105","title":"Reciprocal interactions between neuropeptide F and RYamide regulate host attraction in the mosquito Aedes aegypti.","authors":"Dou, Xiaoyi; Chen, Kangkang; Brown, Mark R; Strand, Michael R","year":2024,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 121(28), e2408072121","doi":"10.1073/pnas.2408072121","pmid":"38950363","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08106","title":"GLP-1 Receptor Agonists and Diabetic Kidney Disease: A Game Charger in the Field?","authors":"Doumani, Georgia; Theofilis, Panagiotis; Tsimihodimos, Vasilis; Kalaitzidis, Rigas G","year":2024,"journal":"Life (Basel, Switzerland), 14(11)","doi":"10.3390/life14111478","pmid":"39598276","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08107","title":"The GLP-1R as a model for understanding and exploiting biased agonism in next-generation medicines.","authors":"Douros, Jonathan D; Mokrosinski, Jacek; Finan, Brian","year":2024,"journal":"The Journal of endocrinology, 261(2)","doi":"10.1530/JOE-23-0226","pmid":"38451873","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review highlights that tirzepatide exhibits a biased signaling profile at the GLP-1 receptor, characterized by preferential Gαs activation over β-arrestin recruitment. This biased signaling appears to contribute to tirzepatide's superior insulinotropic and weight-reducing effects compared to balanced GLP-1R agonists in preclinical models.\n\nThis represents a significant finding because it demonstrates that subtle differences in how a drug interacts with the same receptor can produce clinically meaningful differences in efficacy — moving biased agonism from a theoretical concept to a practical design principle for drug development. The review also catalogues other biased GLP-1R agonists in industry pipelines and their structural determinants.","whyItMatters":"GLP-1 drugs are among the most prescribed medications in the world, yet we're only beginning to understand why some work better than others. This review provides a mechanistic explanation for tirzepatide's clinical superiority — it's not just about hitting two receptors (GLP-1R and GIPR), but about how it signals through the GLP-1R differently. This insight could reshape how pharmaceutical companies design the next wave of obesity and diabetes drugs, potentially leading to more effective medicines with fewer side effects.","specificNumbers":"","methodology":"This is a comprehensive review and meta-analysis of published data on biased agonism at the GLP-1 receptor. The authors examine three categories of bias: ligand-mediated bias (different drugs activating different pathways), receptor-mediated bias (mutations or modifications changing signaling preference), and systems/cell-type bias (the same drug signaling differently in different tissues). They also analyze structural determinants of receptor-ligand interactions that drive biased signaling.","limitations":"As a review, this paper does not present new experimental data. Much of the evidence for clinical relevance of biased agonism comes from preclinical models, and direct proof that biased signaling drives tirzepatide's human clinical advantages has not been definitively established. The complexity of measuring and comparing bias across different assay systems makes it difficult to draw firm conclusions, and biased signaling in isolated cells may not fully predict effects in whole organisms."},{"rthcId":"RPEP-08108","title":"Cell-penetrating peptides with nanoparticles hybrid delivery vectors and their uptake pathways.","authors":"Dowaidar, Moataz","year":2024,"journal":"Mitochondrion, 78, 101906","doi":"10.1016/j.mito.2024.101906","pmid":"38797356","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08109","title":"Uptake pathways of cell-penetrating peptides in the context of drug delivery, gene therapy, and vaccine development.","authors":"Dowaidar, Moataz","year":2024,"journal":"Cellular signalling, 117, 111116","doi":"10.1016/j.cellsig.2024.111116","pmid":"38408550","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08110","title":"Exenatide improves cisplatin induced ovarian damage through NLRP3, Nrf-2, and TLR4 pathways.","authors":"Doğan, Gül O; Erbaş, Oytun","year":2024,"journal":"Cirugia y cirujanos, 93(1), 35-40","doi":"10.24875/CIRU.23000304","pmid":"39383838","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In rats receiving cisplatin chemotherapy for 5 weeks:\n\nExenatide-treated group (Group 2) vs cisplatin-only group (Group 1):\n- Significantly higher numbers of primordial, primary, secondary, and tertiary follicles\n- Significantly lower ovarian fibrosis percentage\n- Higher plasma anti-Mullerian hormone (indicating better preserved ovarian reserve)\n- Lower NLRP3 inflammasome levels (reduced inflammation)\n- Lower TLR4 levels (reduced innate immune activation)\n- Lower Nrf-2 levels (indicating less oxidative stress burden)\n\nExenatide-treated rats had ovarian parameters closer to the healthy control group (Group 0), demonstrating meaningful protection.","whyItMatters":"Chemotherapy-induced ovarian damage is a devastating side effect for young women with cancer, often leading to premature menopause and infertility. Currently, there are limited options to protect ovaries during chemotherapy beyond freezing eggs or embryos. If exenatide — an already-approved drug with a well-known safety profile — can protect ovarian function, it could be repurposed as a fertility-preserving treatment during cancer therapy.","specificNumbers":"","methodology":"Twenty-one female Wistar rats were divided into three groups: healthy controls (n=7), cisplatin + saline (n=7), and cisplatin + exenatide 20 μg/kg/day (n=7). Cisplatin was administered intraperitoneally twice weekly for 5 weeks to create ovarian damage. Outcomes included follicle counts at all developmental stages, ovarian fibrosis assessment, plasma anti-Mullerian hormone levels, and inflammatory pathway markers (NLRP3, Nrf-2, TLR4).","limitations":"This is a small animal study with only 7 rats per group. The cisplatin dosing protocol may not perfectly replicate clinical chemotherapy regimens used in humans. The 5-week duration is short, and long-term ovarian function was not assessed. The study did not evaluate whether fertility was actually preserved (no mating/pregnancy outcomes). The exenatide dose used (20 μg/kg) may not directly translate to human dosing. No human studies of GLP-1 drugs for ovarian protection have been conducted."},{"rthcId":"RPEP-08111","title":"Case Series: Exposure to Glucagon-like Peptide-1 Receptor Agonist in the First Trimester of Pregnancy in Two Siblings.","authors":"Doğan, Şerife Ezgi; Kuşkonmaz, Şerife Mehlika; Koc, Gonul; Aypar, Ebru; Çulha, Cavit","year":2024,"journal":"Endocrine, metabolic & immune disorders drug targets, 24(10), 1237-1239","doi":"10.2174/0118715303252109231023115112","pmid":"37937565","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08112","title":"Metabolic Changes Following Smoking Cessation in Patients with Type 2 Diabetes Mellitus.","authors":"Driva, Stamatina; Korkontzelou, Aliki; Tonstad, Serena; Tentolouris, Nikolaos; Litsiou, Eleni; Vasileiou, Vasiliki; Vassiliou, Alice G; Saltagianni, Vassiliki; Katsaounou, Paraskevi","year":2024,"journal":"Biomedicines, 12(8)","doi":"10.3390/biomedicines12081882","pmid":"39200346","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"After 3 months of varenicline-assisted smoking cessation in patients with T2DM/prediabetes, the 32 successful quitters showed no significant weight gain, no worsening of glycemic control, and significant improvements in lipid profile (total cholesterol 168→156 mg/dL, p=0.013; LDL 96→83 mg/dL, p=0.013). GLP-1 levels rose significantly (39.6→45.8 pM, p=0.016) and leptin increased (11→13.8 ng/dL, p=0.004). Physical activity also increased, with moderate-intensity activity participation rising from 28% to 56% (p=0.039).","whyItMatters":"Fear of weight gain is one of the biggest barriers to smoking cessation in people with diabetes, where extra weight could worsen blood sugar control. This study provides reassuring evidence that quitting with varenicline doesn't cause weight gain or glycemic deterioration in this population, and the significant rise in GLP-1 — a peptide that regulates appetite and insulin — suggests a favorable metabolic shift that may help explain why weight stayed stable.","specificNumbers":"","methodology":"Prospective observational study enrolling 53 patients with T2DM or prediabetes in a smoking cessation program. Thirty-two successfully quit after a 3-month course of varenicline and were followed for an additional month off medication. Measurements at baseline, 2.5 months, and 4 months included body weight, blood pressure, resting metabolic rate, HbA1c, fasting glucose, lipids, CRP, appetite-related hormones (leptin, GLP-1), and self-reported physical activity.","limitations":"Small sample size (32 successful quitters analyzed), no control group, and short follow-up (4 months total). The observational design cannot separate the effects of varenicline from the effects of smoking cessation itself on metabolic parameters. Self-reported physical activity is subject to bias. Longer follow-up would be needed to determine whether the metabolic benefits and weight stability persist."},{"rthcId":"RPEP-08113","title":"Disengagement of somatostatin neurons from lateral septum circuitry by oxytocin and vasopressin restores social-fear extinction and suppresses aggression outbursts in Prader-Willi syndrome model.","authors":"Dromard, Yann; Borie, Amélie M; Chakraborty, Prabahan; Muscatelli, Françoise; Guillon, Gilles; Desarménien, Michel G; Jeanneteau, Freddy","year":2024,"journal":"Biological psychiatry, 95(8), 785-799","doi":"10.1016/j.biopsych.2023.10.016","pmid":"38952926","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In normal mice, oxytocin (OXT) and vasopressin (AVP) from the supraoptic nucleus promote inhibitory transmission in the lateral septum, keeping somatostatin (SST) neurons suppressed. In the Magel2 knockout mouse model of PWS, this neuropeptide signaling fails, causing SST neurons to become disinhibited. This disrupts social-fear extinction and triggers aggressive behavior.\n\nThe deficit mapped specifically to the supraoptic nucleus → lateral septum pathway. Optogenetic or pharmacological inhibition of SST neurons in the LS corrected social-fear extinction deficits and suppressed aggression outbursts, demonstrating a direct causal link and a potential therapeutic target.","whyItMatters":"Intranasal oxytocin has been explored as a treatment for social behavior problems in PWS and autism, but the brain mechanisms have been unclear. This study identifies the specific neural circuit — OXT/AVP → lateral septum SST neurons — and shows exactly how neuropeptide deficits cause social behavior disruptions. This provides a rational basis for developing targeted therapies that go beyond simply spraying oxytocin into the nose.","specificNumbers":"","methodology":"Researchers used the Magel2 knockout mouse model of PWS crossed with Cre-dependent transgenic lines for cell-type-specific manipulation. They employed optogenetics to activate or silence specific neural pathways, electrophysiology to measure synaptic transmission in the lateral septum, and pharmacological interventions in a social-fear-conditioning behavioral paradigm. Pathway-specific roles of OXT and AVP were mapped using circuit-tracing techniques.","limitations":"This is a mouse study using a genetic model of PWS that may not perfectly replicate the human condition. The social-fear conditioning paradigm is a simplified model of complex human social behavior. While optogenetic and pharmacological manipulations are powerful, their translation to human therapies is not straightforward. The specific role of OXT versus AVP was not fully disentangled. Results from the Magel2KO model may not generalize to all forms of PWS or autism."},{"rthcId":"RPEP-08114","title":"Efficacy and Safety of GLP-1 Medicines for Type 2 Diabetes and Obesity.","authors":"Drucker, Daniel J","year":2024,"journal":"Diabetes care, 47(11), 1873-1888","doi":"10.2337/dci24-0003","pmid":"38843460","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review establishes that GLP-1RA have proven cardiorenal benefits beyond glucose and weight control in select populations. Key safety topics addressed include:\n\n- **Muscle and bone**: GLP-1 drugs cause some muscle loss alongside fat loss, with emerging data on bone density and fracture risk\n- **GI motility**: Slowed gastric emptying raises concerns about retained stomach contents before anesthesia\n- **Pancreas and biliary tract**: Ongoing monitoring for pancreatitis and gallbladder disorders\n- **Cancer risk**: Current evidence assessed across multiple cancer types\n- **Exercise capacity**: How weight loss affects physical performance\n\nNext-generation molecules discussed include tirzepatide (GIP-GLP-1 coagonist), maritide (GIP blocker + GLP-1 activator), retatrutide and survodutide (glucagon + GLP-1 activators), each with distinct pharmacological profiles.","whyItMatters":"With millions of people now taking GLP-1 drugs and new indications constantly emerging, a comprehensive safety and efficacy review by one of the field's leading experts is essential. This review cuts through conflicting media reports to provide an evidence-based assessment of what's known and unknown about GLP-1 medicine risks — information critical for both patients and prescribers.","specificNumbers":"","methodology":"This was an expert narrative review published in Diabetes Care by Daniel Drucker, a foundational researcher in GLP-1 biology. The review synthesizes clinical trial data, post-marketing surveillance, and ongoing trial evidence across multiple GLP-1 medicines and indications.","limitations":"As a single-author narrative review, the evidence synthesis reflects one expert's perspective rather than a systematic methodology. Some safety questions (long-term cancer risk, bone fracture rates) remain unanswered due to insufficient long-term data. The review was published in 2024, and new safety signals or trial results may have emerged since."},{"rthcId":"RPEP-08115","title":"Bioactive Peptides and Other Immunomodulators of Mushroom Origin.","authors":"Drzewiecka, Beata; Wessely-Szponder, Joanna; Świeca, Michał; Espinal, Paula; Fusté, Ester; Fernández-De La Cruz, Eric","year":2024,"journal":"Biomedicines, 12(7)","doi":"10.3390/biomedicines12071483","pmid":"39062056","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08116","title":"Effects of liraglutide on abdominal fat distribution and glucose metabolism in Chinese subjects with obesity.","authors":"Du, Mengyang; Yue, Jiang; Qi, Yicheng; He, Shengyun; Lu, Xiaobing; Yang, Minglan; Wang, Lihua; Lu, Qing; Ma, Jing","year":2024,"journal":"Diabetology & metabolic syndrome, 16(1), 307","doi":"10.1186/s13098-024-01540-4","pmid":"39707524","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"After 12 weeks of liraglutide monotherapy (0.6-1.8 mg/day) in 71 obese subjects:\n\n- Significant weight loss (p<0.001)\n- Fasting blood glucose, 2-hour post-load glucose, and HbA1c all significantly improved (all p<0.001)\n- Subcutaneous adipose tissue (SAT): significantly reduced (p<0.001)\n- Visceral adipose tissue (VAT): significantly reduced (p<0.001)\n- Liver fat content (LFC): significantly reduced (p<0.001)\n\nSubgroup analysis:\n- Patients with impaired glucose regulation (IGR) had higher baseline liver fat than those with normal glucose tolerance (NGT) (p=0.002)\n- IGR patients showed significantly greater liver fat reduction than NGT patients (p<0.001)\n- Liver fat reduction correlated with fasting glucose improvement (r=0.587, p<0.001) and HbA1c improvement (r=0.607, p<0.001)","whyItMatters":"Non-alcoholic fatty liver disease (NAFLD) affects roughly 25% of the global population and is a leading cause of liver cirrhosis. This study provides MRI-based evidence that liraglutide effectively reduces liver fat in obese patients — and that the patients who benefit most are those with pre-diabetes, who also have the highest liver fat. This supports using GLP-1 medications as a targeted therapy for obese patients with fatty liver and metabolic syndrome.","specificNumbers":"","methodology":"Prospective single-arm clinical study in 71 obese Chinese subjects receiving liraglutide monotherapy (titrated from 0.6 mg to 1.8 mg daily) for 12 weeks. Clinical assessments, blood tests, and MRI examinations were performed at baseline and 12 weeks. MRI measured abdominal fat distribution using proton-density fat fraction (PDFF) — a precise quantitative technique for liver fat, visceral fat, and subcutaneous fat.","limitations":"This is a single-arm study without a placebo control group, so the observed improvements cannot be definitively attributed to liraglutide versus natural lifestyle changes or regression to the mean. The sample size is relatively small (n=71). The 12-week duration may not reflect long-term outcomes. The study population was exclusively Chinese, limiting generalizability. Specific liraglutide doses within the 0.6-1.8 mg range were not analyzed separately. No liver biopsy was performed to assess inflammation or fibrosis changes."},{"rthcId":"RPEP-08117","title":"ACE inhibitory peptides from enzymatic hydrolysate of fermented black sesame seed: Random forest-based optimization, screening, and molecular docking analysis.","authors":"Du, Tonghao; Xu, Yazhou; Xu, Xiaoyan; Xiong, Shijin; Zhang, Linli; Dong, Biao; Huang, Jinqing; Huang, Tao; Xiao, Muyan; Xiong, Tao; Xie, Mingyong","year":2024,"journal":"Food chemistry, 437(Pt 2), 137921","doi":"10.1016/j.foodchem.2023.137921","pmid":"37944395","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08118","title":"Effects of fermentation with Lactiplantibacillus plantarum NCU116 on the antihypertensive activity and protein structure of black sesame seed.","authors":"Du, Tonghao; Huang, Jinqing; Xu, Xiaoyan; Xiong, Shijin; Zhang, Linli; Xu, Yazhou; Zhao, Xueting; Huang, Tao; Xiao, Muyan; Xiong, Tao; Xie, Mingyong","year":2024,"journal":"International journal of biological macromolecules, 262(Pt 1), 129811","doi":"10.1016/j.ijbiomac.2024.129811","pmid":"38302018","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08119","title":"Application research of novel peptide mitochondrial-targeted antioxidant SS-31 in mitigating mitochondrial dysfunction.","authors":"Du, Xinrong; Zeng, Qin; Luo, Yunchang; He, Libing; Zhao, Yuhong; Li, Ninjing; Han, Changli; Zhang, Guohui; Liu, Weixin","year":2024,"journal":"Mitochondrion, 75, 101846","doi":"10.1016/j.mito.2024.101846","pmid":"38237649","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08120","title":"A real-world disproportionality analysis of semaglutide: Post-marketing pharmacovigilance data.","authors":"Du, Yikuan; Zhang, Mengting; Wang, Zhenjie; Hu, Mianda; Xie, Dongxia; Wang, Xiuzhu; Guo, Zhuoming; Zhu, Jinfeng; Zhang, Weichui; Luo, Ziyi; Yang, Chun","year":2024,"journal":"Journal of diabetes investigation, 15(10), 1422-1433","doi":"10.1111/jdi.14229","pmid":"38943656","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08121","title":"Crowdsourcing-Based Knowledge Graph Construction for Drug Side Effects Using Large Language Models with an Application on Semaglutide.","authors":"Duan, Zhijie; Wei, Kai; Xue, Zhaoqian; Zhou, Jiayan; Yang, Shu; Ma, Siyuan; Jin, Jin; Li, Lingyao","year":2024,"journal":"AMIA ... Annual Symposium proceedings. AMIA Symposium, 2024, 332-341","doi":null,"pmid":"41726410","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08122","title":"Somatostatin Receptor Imaging with [18F]FET-βAG-TOCA PET/CT and [68Ga]Ga-DOTA-Peptide PET/CT in Patients with Neuroendocrine Tumors: A Prospective, Phase 2 Comparative Study.","authors":"Dubash, Suraiya; Barwick, Tara D; Kozlowski, Kasia; Rockall, Andrea G; Khan, Sairah; Khan, Sameer; Yusuf, Siraj; Lamarca, Angela; Valle, Juan W; Hubner, Richard A; McNamara, Mairéad G; Frilling, Andrea; Tan, Tricia; Wernig, Florian; Todd, Jeannie; Meeran, Karim; Pratap, Bhavesh; Azeem, Saleem; Huiban, Michael; Keat, Nicholas; Lozano-Kuehne, Jingky P; Aboagye, Eric O; Sharma, Rohini","year":2024,"journal":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 65(3), 416-22","doi":"10.2967/jnumed.123.266601","pmid":"38331457","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 45 patients with grade 1-2 neuroendocrine tumors, [18F]FET-βAG-TOCA PET/CT was noninferior to [68Ga]Ga-DOTA-peptide PET/CT. Both tracers detected 285 lesions with excellent SUVmax correlation (r = 0.91). The fluorine-18 tracer detected 13 additional tumor deposits in 8 patients that the gallium-68 scan missed, while the gallium-68 tracer found 7 additional lesions in 5 patients. The only significant difference was in liver metastases, where the gallium-68 tracer showed better tumor-to-background ratios (3.5 vs. 2.5, p<0.05).","whyItMatters":"Gallium-68-labeled peptide scans are the gold standard for neuroendocrine tumor imaging but are limited by gallium-68's short half-life (68 minutes) and the need for specialized generators. Fluorine-18 has a longer half-life (110 minutes) and is produced by widely available cyclotrons, meaning this new peptide tracer could dramatically expand access to somatostatin receptor imaging worldwide.","specificNumbers":"","methodology":"This was a prospective, phase 2 noninferiority study. Forty-five patients with histologically confirmed grade 1-2 neuroendocrine tumors underwent PET/CT imaging with both tracers within a 6-month window (median 77 days apart). Whole-body scans were performed 50 minutes after injection of 165 MBq of the fluorine-18 tracer. Two unblinded readers evaluated tracer uptake, and three experienced readers performed a randomized, blinded reading at the regional level.","limitations":"The sample size of 45 patients is relatively small for a noninferiority study. The median 77-day gap between scans means disease could have progressed between imaging sessions. The fluorine-18 tracer showed lower tumor-to-background ratios in the liver, which could limit its utility for detecting liver metastases specifically. Readers were unblinded for the primary analysis."},{"rthcId":"RPEP-08123","title":"Glucagon-like peptide-1 receptor agonist-based agents and weight loss composition: Filling the gaps.","authors":"Dubin, Robert L; Heymsfield, Steven B; Ravussin, Eric; Greenway, Frank L","year":2024,"journal":"Diabetes, obesity & metabolism, 26(12), 5503-5518","doi":"10.1111/dom.15913","pmid":"39344838","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08124","title":"Oligoarginine peptide structure and its effect on cell penetration in ocular drug delivery.","authors":"Duca, Stefana; Nikoi, Naa Dei; Berrow, Madeline; Barber, Lois; Slope, Louise N; Peacock, Anna F A; de Cogan, Felicity","year":2024,"journal":"Heliyon, 10(15), e35109","doi":"10.1016/j.heliyon.2024.e35109","pmid":"39170441","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08125","title":"Real-world Impact of 3 and 4.5 mg Doses of Dulaglutide on Weight and Hemoglobin A1c in Patients With Type 2 Diabetes Mellitus.","authors":"Duong, Amy; Heacock, Samantha; Amering, Sarah; Brennan, Lillian; Venci, Jineane; Acquisto, Nicole M","year":2024,"journal":"The Annals of pharmacotherapy, 58(6), 589-597","doi":"10.1177/10600280231199852","pmid":"37743669","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08126","title":"Divergent neural nodes are species- and hormone-dependent in the brood parasitic brain.","authors":"Duque, Fernanda G; Azam, Asma; Kaur, Amanpreet; Pao, Rachel; Lynch, Kathleen S","year":2024,"journal":"Genes, brain, and behavior, 23(5), e12907","doi":"10.1111/gbb.12907","pmid":"39246030","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08127","title":"Semaglutide Treatment Effects on Liver Fat Content in Obese Subjects with Metabolic-Associated Steatotic Liver Disease (MASLD).","authors":"Dusilová, Tereza; Kovář, Jan; Laňková, Ivana; Thieme, Lenka; Hubáčková, Monika; Šedivý, Petr; Pajuelo, Dita; Burian, Martin; Dezortová, Monika; Miklánková, Denisa; Malínská, Hana; Svobodová Šťastná, Petra; Poledne, Rudolf; Hájek, Milan; Haluzík, Martin","year":2024,"journal":"Journal of clinical medicine, 13(20)","doi":"10.3390/jcm13206100","pmid":"39458050","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08128","title":"Effectiveness of Oral Semaglutide in Management of Type 2 Diabetes: A Real-World Study from India.","authors":"Dutta, Aditya; Mahendru, Shama; Sharma, Rutuja; Mithal, Ambrish","year":2024,"journal":"Indian journal of endocrinology and metabolism, 28(6), 653-658","doi":"10.4103/ijem.ijem_266_24","pmid":"39881769","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08129","title":"Efficacy and Safety of Cagrilintide Alone and in Combination with Semaglutide (Cagrisema) as Anti-Obesity Medications: A Systematic Review and Meta-Analysis.","authors":"Dutta, Deep; Nagendra, Lakshmi; Harish, B G; Sharma, Meha; Joshi, Ameya; Hathur, Basavanagowdappa; Kamrul-Hasan, Abm","year":2024,"journal":"Indian journal of endocrinology and metabolism, 28(5), 436-444","doi":"10.4103/ijem.ijem_45_24","pmid":"39676787","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Key results from 3 RCTs with 430 participants:\n\n**CagriSema vs semaglutide 2.4 mg (20-32 weeks):**\n- Extra percentage weight loss: -9.07% (95% CI: -11.91 to -6.23)\n- Extra absolute weight loss: -9.11 kg (95% CI: -12.84 to -5.39)\n- GI adverse events and vomiting were significantly higher with CagriSema\n\n**Cagrilintide 2.4 mg vs semaglutide/liraglutide (26-32 weeks):**\n- Percentage weight loss: similar (MD -1.83%, non-significant, p=0.11)\n- Absolute weight loss: similar (MD -1.88 kg, non-significant, p=0.12)\n- Vomiting was significantly lower with cagrilintide\n\nTreatment-emergent and serious adverse events were comparable across all groups.","whyItMatters":"CagriSema represents the next frontier in peptide-based obesity treatment — combining two different appetite-suppressing peptide pathways (GLP-1 and amylin) in a single weekly injection. The finding that it outperforms semaglutide alone by a substantial 9 kg is remarkable, as semaglutide was already considered the gold standard. This combination could set new benchmarks for non-surgical weight loss.","specificNumbers":"","methodology":"Systematic review and meta-analysis searching electronic databases for randomized controlled trials of cagrilintide alone or CagriSema in obese individuals compared to placebo or active comparators. Three RCTs with 430 participants were included. Primary outcomes were body weight changes; secondary outcomes included glycemia, lipids, and adverse events.","limitations":"Only 3 RCTs with 430 participants were available for analysis — a small evidence base for a meta-analysis. High heterogeneity (I² = 96-98%) across studies suggests inconsistency in effect sizes, limiting confidence in the pooled estimates. Study durations were relatively short (20-32 weeks), and long-term efficacy and safety remain unknown. The increased GI side effects with CagriSema may limit tolerability for some patients."},{"rthcId":"RPEP-08130","title":"Efficacy and Safety of Novel Twincretin Tirzepatide, a Dual GIP/GLP-1 Receptor Agonist, as an Anti-obesity Medicine in Individuals Without Diabetes: A Systematic Review and Meta-analysis.","authors":"Dutta, Deep; Kamrul-Hasan, A B M; Nagendra, Lakshmi; Bhattacharya, Saptarshi","year":2024,"journal":"TouchREVIEWS in endocrinology, 20(2), 72-80","doi":"10.17925/EE.2024.20.2.10","pmid":"39526060","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08131","title":"Glucagon-Like Peptide-1 Receptor Agonists in Post-bariatric Surgery Patients: A Systematic Review and Meta-analysis.","authors":"Dutta, Deep; Nagendra, Lakshmi; Joshi, Ameya; Krishnasamy, Suryashri; Sharma, Meha; Parajuli, Naresh","year":2024,"journal":"Obesity surgery, 34(5), 1653-1664","doi":"10.1007/s11695-024-07175-8","pmid":"38502519","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 8 studies and 557 individuals, liraglutide produced significantly greater weight loss than placebo after 6 months: -6.0 kg (95% CI: -8.66 to -3.33; p<0.001). Semaglutide outperformed liraglutide at both 6 months (-2.57% body weight difference; 95% CI: -3.91 to -1.23) and 12 months (-4.15% body weight difference; 95% CI: -6.96 to -1.34; p=0.004).\n\nSemaglutide users were significantly more likely to achieve >15% weight loss (OR 2.15; p=0.03) and >10% weight loss (OR 2.10; p=0.01) at 12 months compared to liraglutide. Liraglutide significantly reduced fat mass (-4.78 kg). However, the authors noted that bone health deterioration and muscle mass loss remain concerns requiring further evaluation.","whyItMatters":"Up to 20-30% of bariatric surgery patients experience significant weight regain, and until recently there were few effective medical options. This is the first meta-analysis to evaluate GLP-1 drugs specifically in post-bariatric patients, providing evidence that these peptide therapies can rescue weight loss when surgery alone falls short. The finding that semaglutide outperforms liraglutide in this population gives clinicians guidance on which GLP-1 drug to choose.","specificNumbers":"","methodology":"Systematic review and meta-analysis registered in PROSPERO (CRD42023473991). Researchers searched multiple databases for randomized controlled trials, case-control, cohort, and observational studies evaluating GLP-1 receptor agonists in post-bariatric surgery patients. From 1,759 initially screened articles, 8 studies with 557 individuals met inclusion criteria. Primary outcome was weight loss after at least 3 months of therapy. Secondary outcomes included body composition changes, total adverse events, and serious adverse events.","limitations":"Only 8 studies with 557 total participants were available, limiting statistical power. High heterogeneity (I²=79%) was observed in the liraglutide vs placebo analysis. The studies included a mix of RCTs and observational designs, introducing potential bias. Long-term data beyond 12 months was limited. The meta-analysis could not fully assess safety outcomes including bone density changes and sarcopenia risk. Different bariatric procedures (sleeve, bypass, etc.) were pooled together, though they may respond differently to GLP-1 therapy."},{"rthcId":"RPEP-08132","title":"Orforglipron, a novel non-peptide oral daily glucagon-like peptide-1 receptor agonist as an anti-obesity medicine: A systematic review and meta-analysis.","authors":"Dutta, Deep; Nagendra, Lakshmi; Anne, Beatrice; Kumar, Manoj; Sharma, Meha; Kamrul-Hasan, A B M","year":2024,"journal":"Obesity science & practice, 10(2), e743","doi":"10.1002/osp4.743","pmid":"38414573","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08133","title":"Cathelicidins: Opportunities and Challenges in Skin Therapeutics and Clinical Translation.","authors":"Dzurová, Lenka; Holásková, Edita; Pospíšilová, Hana; Schneider Rauber, Gabriela; Frébortová, Jitka","year":2024,"journal":"Antibiotics (Basel, Switzerland), 14(1)","doi":"10.3390/antibiotics14010001","pmid":"39858288","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies cathelicidins' therapeutic potential across multiple skin conditions:\n- **Infections**: Broad-spectrum activity against bacteria, viruses, and fungi, including antibiotic-resistant strains\n- **Wound healing**: LL-37 promotes wound closure and skin barrier restoration, particularly relevant for diabetic foot ulcers\n- **Cancer**: Some cathelicidins show anti-melanoma activity\n- **Acne**: Antimicrobial and anti-inflammatory effects relevant to acne pathology\n\nHowever, significant translational barriers exist: many peptide therapies have failed clinical trials due to unclear efficacy and safety; bacterial resistance to cathelicidins has emerged (contradicting initial claims); large-scale production is costly; drug stability and delivery formulation remain challenging.","whyItMatters":"As antibiotic resistance becomes a global crisis, the need for new antimicrobial approaches has never been greater. Cathelicidins offer a fundamentally different mechanism from conventional antibiotics and could address hard-to-treat skin infections. However, the honest assessment of clinical translation challenges presented here — including the uncomfortable truth about bacterial resistance developing against these 'natural' antibiotics — is essential for directing research resources effectively.","specificNumbers":"","methodology":"This is a comprehensive review of published research on cathelicidin antimicrobial peptides, their biological functions in skin immunity, therapeutic applications for skin diseases, and the challenges preventing clinical translation. The authors examine evidence from preclinical studies, clinical trial outcomes, and pharmaceutical development literature.","limitations":"As a review, no new experimental data is presented. The therapeutic applications discussed are largely based on preclinical data, with limited successful clinical translation. The review acknowledges but does not fully resolve the tension between cathelicidins' dual roles as antimicrobials and pro-inflammatory mediators (particularly relevant in conditions like rosacea where LL-37 overexpression is pathological). Specific clinical trial failure details and success rates are not quantified."},{"rthcId":"RPEP-08134","title":"Restoration of the Ultrastructural Integrity of the Dermal Collagen Network by 12-Week Ingestion of Special Collagen Peptides.","authors":"Dähnhardt, Dorothee; Dähnhardt-Pfeiffer, Stephan; Segger, Dörte; Poeggeler, Burkhard; Lemmnitz, Gunter","year":2024,"journal":"Dermatology and therapy, 14(9), 2509-2521","doi":"10.1007/s13555-024-01251-8","pmid":"39150674","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08135","title":"Biomedical applications of synthetic peptides derived from venom of animal origin: A systematic review.","authors":"Díaz-Gómez, Jorge L; Martín-Estal, Irene; Rivera-Aboytes, Elizabeth; Gaxiola-Muñíz, Ramón Alonso; Puente-Garza, César A; García-Lara, Silverio; Castorena-Torres, Fabiola","year":2024,"journal":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 170, 116015","doi":"10.1016/j.biopha.2023.116015","pmid":"38113629","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08136","title":"Intra-arterial peptide-receptor radionuclide therapy for neuro-endocrine tumour liver metastases: an in-patient randomised controlled trial (LUTIA).","authors":"Ebbers, S C; Barentsz, M W; de Vries-Huizing, D M V; Versleijen, M W J; Klompenhouwer, E G; Tesselaar, M E T; Stokkel, M P M; Brabander, T; Hofland, J; Moelker, A; van Leeuwaarde, R S; Smits, M L J; Braat, A J A T; Lam, M G E H","year":2024,"journal":"European journal of nuclear medicine and molecular imaging, 51(4), 1121-1132","doi":"10.1007/s00259-023-06467-y","pmid":"37897617","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08137","title":"Validation of the standardization framework SSTR-RADS 1.0 for neuroendocrine tumors using the novel SSTR‑targeting peptide [18F]SiTATE.","authors":"Ebner, R; Lohse, A; Fabritius, M P; Rübenthaler, J; Wängler, C; Wängler, B; Schirrmacher, R; Völter, F; Schmid, H P; Unterrainer, L M; Öcal, O; Hinterberger, A; Spitzweg, C; Auernhammer, C J; Geyer, T; Ricke, J; Bartenstein, P; Holzgreve, A; Grawe, F","year":2024,"journal":"European radiology, 34(11), 7222-7232","doi":"10.1007/s00330-024-10788-3","pmid":"38769164","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08138","title":"Structure-aware deep learning model for peptide toxicity prediction.","authors":"Ebrahimikondori, Hossein; Sutherland, Darcy; Yanai, Anat; Richter, Amelia; Salehi, Ali; Li, Chenkai; Coombe, Lauren; Kotkoff, Monica; Warren, René L; Birol, Inanc","year":2024,"journal":"Protein science : a publication of the Protein Society, 33(7), e5076","doi":"10.1002/pro.5076","pmid":"39196703","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08139","title":"Once-weekly semaglutide in people with HIV-associated lipohypertrophy: a randomised, double-blind, placebo-controlled phase 2b single-centre clinical trial.","authors":"Eckard, Allison Ross; Wu, Qian; Sattar, Abdus; Ansari-Gilani, Kianoush; Labbato, Danielle; Foster, Theresa; Fletcher, Aaron A; Adekunle, Ruth O; McComsey, Grace A","year":2024,"journal":"The lancet. Diabetes & endocrinology, 12(8), 523-534","doi":"10.1016/S2213-8587(24)00150-5","pmid":"38964353","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide produced a statistically significant reduction in abdominal visceral adipose tissue of 30.82 cm² (95% CI: -50.13 to -11.51), representing a 30.6% decrease compared to placebo over 32 weeks. Abdominal subcutaneous fat also decreased by 42.01 cm² (11.2% reduction), and total body fat dropped by 18.9%.\n\nThese reductions occurred without a statistically significant increase in treatment-related adverse events, though one grade 4 elevated lipase event and two cases of cholelithiasis were observed in the semaglutide group.","whyItMatters":"HIV-associated lipohypertrophy has lacked effective treatments despite increasing cardiometabolic risk. This trial provides the first randomized controlled evidence that a GLP-1 receptor agonist peptide can meaningfully reduce visceral fat in this population, potentially opening a new therapeutic avenue for a condition that affects many people living with HIV on long-term antiretroviral therapy.","specificNumbers":"","methodology":"This was a randomized, double-blind, placebo-controlled phase 2b trial conducted at a single US site. 108 adults with HIV, controlled viral load, BMI of 25 or more, and lipohypertrophy (but no diabetes) were randomly assigned 1:1 to receive either semaglutide (titrated over 8 weeks to 1.0 mg weekly for 24 weeks) or placebo by subcutaneous injection. Fat was measured by body compartment at 32 weeks. Analysis followed intention-to-treat principles.","limitations":"This was a single-center trial with a relatively small sample size of 108 participants. All participants were from one US site, limiting generalizability. The study excluded people with diabetes, so results may not apply to HIV patients with concurrent diabetes. The 32-week duration may not capture long-term effects or sustained benefit after stopping treatment. A few serious adverse events (elevated lipase, gallstones) need further evaluation in larger populations."},{"rthcId":"RPEP-08140","title":"The GLP-1 receptor agonist exendin-4 reduces taurine and glycine in nucleus accumbens of male rats, an effect tentatively involving the nucleus tractus solitarius.","authors":"Edvardsson, Christian E; Vestlund, Jesper; Ericson, Mia; Jerlhag, Elisabet","year":2024,"journal":"Frontiers in pharmacology, 15, 1439203","doi":"10.3389/fphar.2024.1439203","pmid":"39221138","tags":["glp-1-agonists"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"The GLP-1 receptor agonist exendin-4 (Ex4) reduced levels of taurine, glycine, and serine in the nucleus accumbens — the brain's reward center — of male rats. The decreases in taurine and glycine appeared to involve GLP-1 receptor activation in the nucleus tractus solitarius (NTS), a brainstem region that relays gut signals to the brain.\n\nSystemic Ex4 injection also elevated metabolites of dopamine (DOPAC and HVA) and serotonin (5HIAA) in the nucleus accumbens. The dopamine-related metabolite increases involved GLP-1 receptors outside the NTS, suggesting multiple brain pathways are involved in how GLP-1 drugs modulate reward-related behavior.","whyItMatters":"GLP-1 drugs like semaglutide and exenatide are increasingly observed to reduce not just appetite but also interest in alcohol, gambling, and other addictive behaviors. This study helps explain the brain chemistry behind these effects by showing that a GLP-1 agonist changes neurotransmitter levels in the reward center. Understanding these mechanisms could open the door to using GLP-1 drugs for addiction treatment.","specificNumbers":"Ex4 reduced taurine, glycine, and serine in nucleus accumbens · elevated DOPAC, HVA, and 5HIAA · NTS involvement confirmed for taurine and glycine effects · systemic and local NTS administration compared","methodology":"This exploratory study used in vivo microdialysis in male rats — a technique that samples brain chemicals in real time through a tiny probe. Exendin-4 was administered either systemically (whole-body injection) or locally into the NTS. Researchers then measured changes in multiple neurotransmitters and their metabolites in the nucleus accumbens, including dopamine, serotonin, noradrenaline, glutamate, GABA, glycine, taurine, and serine.","limitations":"This is a descriptive animal study that shows correlations but cannot prove causality. Only male rats were studied, so sex differences are unknown. The study used exendin-4, which may not perfectly replicate the effects of longer-acting GLP-1 drugs like semaglutide used clinically. The authors explicitly note the descriptive nature of the findings."},{"rthcId":"RPEP-08141","title":"Cardiac Sympathetic Nerve Function in Patients with Severe Aortic Stenosis Prior and After Transcatheter Aortic Valve Implantation: Evaluation by 5-Year Risk Model.","authors":"Egi, Ryuta; Fukushima, Kenji; Matsusaka, Yohji; Yamane, Tomohiko; Seto, Akira; Matsunari, Ichiro; Nakajima, Yoshie; Nakano, Shintaro; Kuji, Ichiei","year":2024,"journal":"Annals of nuclear cardiology, 10(1), 6-15","doi":"10.17996/anc.23-00008","pmid":"39635331","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08142","title":"Activity of the hypothalamic neuropeptide Y increases in adult and decreases in old rats.","authors":"Eitmann, Szimonetta; Füredi, Nóra; Gaszner, Balázs; Kormos, Viktória; Berta, Gergely; Pólai, Fanni; Kovács, Dóra K; Balaskó, Márta; Pétervári, Erika","year":2024,"journal":"Scientific reports, 14(1), 22676","doi":"10.1038/s41598-024-73825-7","pmid":"39349740","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08143","title":"Palliative potential of velutin against abamectin induced cardiac toxicity via regulating JAK1/STAT3, NF-κB, Nrf-2/Keap-1 signaling pathways: An insight from molecular docking.","authors":"El Safadi, Mahmoud; Ahmad, Qurat-Ul-Ain; Majeebullah, Muhammad; Ali, Adnan; Al-Emam, Ahmed; Antoniolli, Giorgio; Shah, Tawaf Ali; Salamatullah, Ahmad Mohammad","year":2024,"journal":"Pesticide biochemistry and physiology, 205, 106117","doi":"10.1016/j.pestbp.2024.106117","pmid":"39477578","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08144","title":"Melittin alcalase-hydrolysate: a novel chemically characterized multifunctional bioagent; antibacterial, anti-biofilm and anticancer.","authors":"El-Didamony, Samia E; Kalaba, Mohamed H; Sharaf, Mohamed H; El-Fakharany, Esmail M; Osman, Ali; Sitohy, Mahmoud; Sitohy, Basel","year":2024,"journal":"Frontiers in microbiology, 15, 1419917","doi":"10.3389/fmicb.2024.1419917","pmid":"39091304","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Melittin, the primary peptide in bee venom, was enzymatically hydrolyzed into smaller bioactive peptide fragments that showed superior anticancer selectivity compared to intact melittin. All tested peptides displayed antibacterial, anti-biofilm, and anticancer activities against both Gram-positive and Gram-negative bacteria and two cancer cell lines (Huh-7 liver cancer and HCT 116 colon cancer). Crucially, neither melittin nor its fragments affected the viability of normal human lung cells (Wi-38), and the hydrolyzed fractions had better selectivity indices (greater cancer cell killing relative to normal cell toxicity) than whole melittin.","whyItMatters":"Melittin's therapeutic potential has been limited by its toxicity to normal cells. This study shows that breaking melittin into smaller peptide fragments using an enzyme (alcalase) creates derivatives that are more selective — killing cancer cells and bacteria while sparing normal human cells. This approach could make venom-derived peptide therapeutics safer and more practical for clinical use.","specificNumbers":"3 peptide fractions (F1, F2, F3) from melittin hydrolysis · active against Gram+ and Gram- bacteria · anti-biofilm activity · inhibited Huh-7 and HCT 116 cancer cells · safe for Wi-38 normal cells · superior selectivity index vs intact melittin","methodology":"Bee venom was collected from honeybee workers, and melittin was extracted and verified by urea-PAGE. Melittin was hydrolyzed with alcalase enzyme, and the hydrolysate was fractionated by gel filtration chromatography into three fractions characterized by ESI mass spectrometry. Fractions were tested for antimicrobial activity, anti-biofilm activity, anticancer effects (against Huh-7 and HCT 116 cell lines), anti-migration activity, and normal cell toxicity (Wi-38 cells).","limitations":"This is an in vitro study — antibacterial and anticancer activities have not been validated in animal models. The mechanisms of action for the peptide fragments were not fully elucidated. Pharmacokinetic properties (stability in blood, tissue distribution) were not assessed. The specific bioactive sequences responsible for the improved selectivity were not individually identified."},{"rthcId":"RPEP-08145","title":"Excimer light effect on neurogenic inflammation in active versus stable psoriasis lesions.","authors":"El-Mesidy, Marwa S; Metwally, Yomna A; Nour, Zeinab A; Elmasry, Maha F","year":2024,"journal":"Lasers in medical science, 39(1), 54","doi":"10.1007/s10103-024-04005-2","pmid":"38296870","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Psoriasis patients had significantly higher tissue levels of substance P compared to healthy controls. Excimer light therapy (9 sessions) reduced both substance P and its receptor (NK-1R) levels in psoriatic skin, along with significant clinical improvements in disease severity (PSI) and itching (VAS). The treatment was effective for both active and stable plaque psoriasis, with no significant difference between groups. This suggests excimer light works partly by dampening neurogenic inflammation mediated by substance P.","whyItMatters":"This study provides evidence that psoriasis is partly driven by neurogenic inflammation through the neuropeptide substance P — and that an existing treatment (excimer light) works by reducing this peptide's activity. Understanding the substance P-psoriasis connection could open the door to targeted peptide-based therapies like NK-1R antagonists for treating psoriasis and the intense itching it causes.","specificNumbers":"n=54 psoriasis patients (27 stable, 27 active) + 10 controls · 9 excimer light sessions · SP levels elevated vs controls · SP and NK-1R decreased after treatment · PSI and VAS improved (p significant) · 43 patients completed treatment","methodology":"Clinical study comparing 27 stable and 27 active psoriasis patients with 10 healthy controls. Disease severity was measured by local psoriasis severity index (PSI) and itching by visual analogue scale (VAS). Tissue levels of substance P and NK-1 receptor were measured by ELISA in skin biopsies before and after 9 excimer light sessions. 43 patients completed the treatment course.","limitations":"The study lacked a sham/placebo control group. Sample size was moderate (54 patients total). Only tissue (not serum) levels of SP and NK-1R were measured. The study cannot determine whether excimer light directly reduces SP or whether SP reduction is secondary to overall disease improvement. Long-term durability of SP reduction and clinical improvement was not assessed."},{"rthcId":"RPEP-08146","title":"Harnessing the potency of scorpion venom-derived proteins: applications in cancer therapy.","authors":"El-Qassas, Jihad; Abd El-Atti, Mahmoud; El-Badri, Nagwa","year":2024,"journal":"Bioresources and bioprocessing, 11(1), 93","doi":"10.1186/s40643-024-00805-0","pmid":"39361208","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08147","title":"Tuning the properties of peptide imprinted nanoparticles for protein immunoprecipitation using magnetic streptavidin beads.","authors":"Elejaga-Jimeno, Ainhoa; Gómez-Caballero, Alberto; García Del Caño, Gontzal; Unceta, Nora; Saumell-Esnaola, Miquel; Sallés, Joan; Goicolea, M Aránzazu; Barrio, Ramón J","year":2024,"journal":"Mikrochimica acta, 191(11), 709","doi":"10.1007/s00604-024-06782-7","pmid":"39470840","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08148","title":"Reductions of food intake and body weight in diet-induced obese rats following chronic treatment with a monomeric peptide multiagonist.","authors":"Elfers, Clinton T; Chichura, Kylie S; Ashlaw, Emily F; Chepurny, Oleg G; Holz, George G; Doyle, Robert P; Roth, Christian L","year":2024,"journal":"Clinical nutrition (Edinburgh, Scotland), 43(7), 1782-1790","doi":"10.1016/j.clnu.2024.05.035","pmid":"38861891","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Over 28 days, GEP44 (a GLP-1R/Y1R/Y2R triple agonist) produced body weight reductions of -15.6% in males and -11.9% in females versus vehicle, compared to -9.7% (males) and -5.1% (females) with liraglutide. Cumulative food intake reductions were also significantly greater: GEP44 reduced intake by -39% in males and -30% in females versus -20% and -10% with liraglutide, respectively.\n\nGlucose tolerance tests showed similar stimulation of glucose-induced insulin secretion between GEP44 and liraglutide, indicating comparable glycemic effects despite the superior weight loss with the triple agonist.","whyItMatters":"Current GLP-1 agonists achieve meaningful weight loss but many patients don't reach their goals. This study demonstrates that a single peptide targeting three complementary pathways can produce substantially greater weight loss than GLP-1 agonism alone. The multi-receptor approach — combining gut hormone and neuropeptide Y pathways — addresses the reality that obesity involves multiple dysregulated systems simultaneously.","specificNumbers":"","methodology":"Diet-induced obese male and female rats received daily injections of GEP44 (triple agonist), liraglutide, or vehicle for 28 days. Body weight, food intake, glucose tolerance (IPGTT at baseline and day 14), and metabolic blood parameters (day 28) were measured. Both sexes were studied to assess potential sex differences in response.","limitations":"This is an animal study that may not translate directly to humans. Rats received daily injections, which differs from the weekly dosing preferred in humans. Side effects (nausea, GI issues) were not comprehensively reported, which is a major concern for GLP-1-based therapies. The 28-day duration is short — sustained effects and safety need longer-term evaluation. The mechanism of weight loss (fat vs lean mass) was not detailed."},{"rthcId":"RPEP-08149","title":"The effect of lacosamide on calcitonin gene-related peptide serum level in episodic migraine patients: a randomized, controlled trial.","authors":"Elgamal, Shimaa; Ahmed, Sherihan Rezk; Nahas, Mohamed M; Hendawy, Shimaa R; Elshafei, Osama; Zeinhom, Mohamed G","year":2024,"journal":"Acta neurologica Belgica, 124(3), 965-972","doi":"10.1007/s13760-024-02499-9","pmid":"38502425","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08150","title":"Confounding Factors in the Association Between Glucagon-Like Peptide-1 Receptor Agonist Use and Retained Gastric Contents in Asymptomatic Patients Undergoing Upper Gastrointestinal Endoscopy: A Retrospective Study.","authors":"Elimihele, Thomas A; Mangrola, Anjali M; Oshomoji, Oluwatobi; Wilson, Nateshia B; Nnamani, Ikenna; Ashong, Bryan; Billings, Sunteasja; Getu, Daniel K; Kumar, Sachin; Maliakkal, Benedict","year":2024,"journal":"Cureus, 16(9), e69152","doi":"10.7759/cureus.69152","pmid":"39398811","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Out of 3,415 patients who underwent upper endoscopy over eight years, 129 (3.8%) had clinically significant delayed gastric emptying (CSDGE) with retained stomach contents.\n\nGLP-1 receptor agonist use was associated with only 2% of CSDGE cases — the lowest frequency among all assessed factors. Opioid use accounted for 35% of cases, the highest contribution.\n\nThe odds ratio for CSDGE in GLP-1 RA users was 2.5, but the confidence interval was wide (95% CI: 0.75-8.29) and crossed 1.0, meaning the association was not statistically significant. Critically, every patient who had CSDGE while on a GLP-1 RA was simultaneously taking other medications or had conditions independently associated with delayed gastric emptying.","whyItMatters":"The recommendation to stop GLP-1 drugs before surgery or procedures has created anxiety for patients and logistical headaches for clinicians. If GLP-1 drugs are not the primary driver of retained stomach contents — and opioids and other factors are far more important — the current blanket recommendation may be overly cautious. This study supports a more nuanced, case-by-case approach that considers all risk factors rather than singling out GLP-1 drugs.","specificNumbers":"","methodology":"Single-center retrospective study spanning eight years. Researchers reviewed records of 3,415 asymptomatic patients who underwent esophagogastroduodenoscopy (EGD) with or without colonoscopy. They identified 129 patients with clinically significant delayed gastric emptying and assessed the contribution of various factors including GLP-1 RA use, opioid use, and other medications or conditions known to affect gastric emptying. The analysis controlled for common confounding factors that previous studies had largely ignored.","limitations":"This is a single-center retrospective study, limiting generalizability. The sample of GLP-1 RA users with CSDGE was very small, resulting in a wide confidence interval that could not achieve statistical significance. The study could not determine whether GLP-1 RA contributed partially to CSDGE in patients with multiple risk factors — only that other factors were always present. Specific GLP-1 RA agents and doses were not differentiated. The eight-year timeframe likely includes periods when GLP-1 RA use was less common, potentially underrepresenting current usage patterns."},{"rthcId":"RPEP-08151","title":"Liraglutide and Colesevelam Change Serum and Fecal Bile Acid Levels in a Randomized Trial With Patients With Bile Acid Diarrhea.","authors":"Ellegaard, Anne-Marie; Kårhus, Martin L; Krych, Lukasz; Sonne, David P; Forman, Julie L; Hansen, Svend H; Dragsted, Lars Ove; Nielsen, Dennis S; Knop, Filip K","year":2024,"journal":"Clinical and translational gastroenterology, 15(11), e00772","doi":"10.14309/ctg.0000000000000772","pmid":"39602188","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08152","title":"Novel Calcitonin Gene-Related Peptide (CGRP) Interfering Migraine Therapies and Stroke-A Review.","authors":"Eller, Michael Thomas; Frank, Florian; Kaltseis, Katharina; Karisik, Anel; Knoflach, Michael; Broessner, Gregor","year":2024,"journal":"International journal of molecular sciences, 25(21)","doi":"10.3390/ijms252111685","pmid":"39519240","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08153","title":"Case series on monoclonal antibodies targeting calcitonin gene-related peptide in migraine patients during pregnancy: Enhancing safety data.","authors":"Elosua-Bayes, Iker; Alpuente, Alicia; Melgarejo, Laura; Caronna, Edoardo; Torres-Ferrús, Marta; Pozo-Rosich, Patricia","year":2024,"journal":"Cephalalgia : an international journal of headache, 44(9), 3331024241273966","doi":"10.1177/03331024241273966","pmid":"39314064","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08154","title":"Evaluation of Kynu, Defb2, Camp, and Penk Expression Levels as Psoriasis Marker in the Imiquimod-Induced Psoriasis Model.","authors":"Emami, Zahra; Shobeiri, Saeideh Sadat; Khorrami, Razia; Haghnavaz, Navideh; Rezaee, Mohammad Ali; Moghadam, Malihe; Pordel, Safoora; Sankian, Mojtaba","year":2024,"journal":"Mediators of inflammation, 2024, 5821996","doi":"10.1155/2024/5821996","pmid":"39045230","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08155","title":"Somatostatin-immunoreactive neurons of the rat gut during the development.","authors":"Emanuilov, Andrey I; Budnik, Antonina F; Masliukov, Petr M","year":2024,"journal":"Histochemistry and cell biology, 162(5), 385-402","doi":"10.1007/s00418-024-02322-9","pmid":"39153131","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08156","title":"Experiences and Translatability of In Vitro and In Vivo Models to Evaluate Caprate as a Permeation Enhancer.","authors":"Emeh, Prosper; Breitholtz, Katarina; Berg, Staffan; Vedin, Charlotta; Englund, Maria; Uggla, Teresia; Antonsson, Malin; Nunes, Filipe; Hilgendorf, Constanze; Bergström, Christel A S; Davies, Nigel","year":2024,"journal":"Molecular pharmaceutics, 21(1), 313-324","doi":"10.1021/acs.molpharmaceut.3c00872","pmid":"38054599","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08157","title":"Satiety Hormone LEAP2 After Low-Calorie Diet With/Without Endobarrier Insertion in Obesity and Type 2 Diabetes Mellitus.","authors":"Emini, Mimoza; Bhargava, Raghav; Aldhwayan, Madhawi; Chhina, Navpreet; Rodriguez Flores, Marcela; Aldubaikhi, Ghadah; Al Lababidi, Moaz; Al-Najim, Werd; Miras, Alexander D; Ruban, Aruchuna; Glaysher, Michael A; Prechtl, Christina G; Byrne, James P; Teare, Julian P; Goldstone, Anthony P","year":2024,"journal":"Journal of the Endocrine Society, 9(1), bvae214","doi":"10.1210/jendso/bvae214","pmid":"39659543","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08158","title":"Endothelial Dysfunction in Obesity and Therapeutic Targets.","authors":"Engin, Atilla","year":2024,"journal":"Advances in experimental medicine and biology, 1460, 489-538","doi":"10.1007/978-3-031-63657-8_17","pmid":"39287863","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08159","title":"Protein Kinases in Obesity, and the Kinase-Targeted Therapy.","authors":"Engin, Atilla","year":2024,"journal":"Advances in experimental medicine and biology, 1460, 199-229","doi":"10.1007/978-3-031-63657-8_7","pmid":"39287853","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08160","title":"Ischaemic Cardiomyopathy Secondary to Asymptomatic Coronary Artery Disease: A Case Report.","authors":"Eni, Gedoni; Ramirez, Allison; Faiz, Roshan; Solano, Jhiamluka","year":2024,"journal":"Cureus, 16(9), e68766","doi":"10.7759/cureus.68766","pmid":"39371706","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08161","title":"Non-canonical amino acid bioincorporation into antimicrobial peptides and its challenges.","authors":"Enninful, George Nkrumah; Kuppusamy, Rajesh; Tiburu, Elvis K; Kumar, Naresh; Willcox, Mark D P","year":2024,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 30(6), e3560","doi":"10.1002/psc.3560","pmid":"38262069","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08162","title":"Photoinduced Hydrogel-Forming Caged Peptides with Improved Solubility.","authors":"Enyedi, Kata N; Basa, Bettina; Mező, Gábor; Lajkó, Eszter","year":2024,"journal":"ACS omega, 9(6), 6894-6900","doi":"10.1021/acsomega.3c08289","pmid":"38371799","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08163","title":"Innovative Glucagon-based Therapies for Obesity.","authors":"Enyew Belay, Kibret; Jemal, Rebil Heiru; Tuyizere, Aloys","year":2024,"journal":"Journal of the Endocrine Society, 8(12), bvae197","doi":"10.1210/jendso/bvae197","pmid":"39574787","tags":["glp-1-agonists","weight-management"],"studyType":"review","evidenceStrength":"review","keyFinding":"This review maps the full landscape of glucagon-based obesity therapies, from single-receptor agonists to the newest triple-agonist drugs. Glucagon — traditionally seen as a blood-sugar-raising hormone — is being reframed as a metabolic multitool that boosts energy expenditure, suppresses appetite, and promotes fat burning.\n\nThe review covers single glucagon receptor agonists, dual agonists (GLP-1/glucagon like survodutide, and GLP-1/GIP like tirzepatide), and the emerging triple agonists that target GLP-1, GIP, and glucagon receptors simultaneously (like retatrutide). It also discusses combination approaches involving amylin, thyroid hormone (T3), FGF21, and peptide YY. Triple agonists show the most potent weight loss in early trials, leveraging the additive metabolic benefits of activating all three receptor pathways.","whyItMatters":"The obesity drug pipeline is rapidly evolving from single-target GLP-1 drugs (semaglutide) to multi-receptor agonists. Understanding why glucagon — a hormone that raises blood sugar — can paradoxically help with weight loss is key to understanding the next generation of metabolic drugs. This review provides a comprehensive map of where the field is heading, explaining why adding glucagon receptor activation to GLP-1 therapy may produce superior weight loss through increased energy expenditure.","specificNumbers":"","methodology":"Narrative review summarizing preclinical and clinical findings on glucagon-based obesity therapies, including single, dual, and triple receptor agonists, with discussion of mechanism of action, safety profiles, and ongoing clinical trials.","limitations":"This is a narrative review without systematic search methodology or meta-analysis. Many of the therapies discussed are in early clinical development, so long-term safety and efficacy data are limited. The review may not capture the most recent trial results published after its preparation."},{"rthcId":"RPEP-08164","title":"Incorporation of Three Extracyclic Arginine Residues into a Melanocortin Macrocyclic Agonist (c[Pro-His-DPhe-Arg-Trp-Dap-Lys(Arg-Arg-Arg-Ac)-DPro]) Decreases Food Intake When Administered Intrathecally or Subcutaneously Compared to a Macrocyclic Ligand Lacking Extracyclic Arginine Residues (c[Pro-His-DPhe-Arg-Trp-Dap-Ala-DPro)].","authors":"Ericson, Mark D; Freeman, Katie T; Larson, Courtney M; Bouchard, Jacob L; John, Kristen; Lunzer, Mary M; Koerperich, Zoe M; Haskell-Luevano, Carrie","year":2024,"journal":"ACS pharmacology & translational science, 7(4), 1114-1125","doi":"10.1021/acsptsci.4c00011","pmid":"38633589","tags":[],"studyType":"preclinical","evidenceStrength":"preliminary","keyFinding":"Adding three arginine amino acids to the outside of a cyclic melanocortin peptide made it more effective at suppressing food intake in mice, both when injected into the spinal canal (intrathecally) and under the skin (subcutaneously). The modified peptide maintained or increased potency at melanocortin receptors in cell-based assays, and the in vivo appetite suppression exceeded what lab tests predicted.\n\nThis arginine-addition strategy was inspired by setmelanotide, an FDA-approved melanocortin drug for genetic obesity that also uses an extracyclic arginine critical for its activity.","whyItMatters":"Melanocortin peptide drugs like setmelanotide treat rare genetic obesity by activating MC4R, but designing more effective versions is an active area of research. This study shows that adding arginine residues — a simple structural modification — can enhance a cyclic peptide's real-world effectiveness beyond what lab tests suggest. This disconnect between in vitro and in vivo results is a critical insight for future melanocortin drug design.","specificNumbers":"3 extracyclic Arg residues · 0–3 Arg variants tested · Equipotent or increased in vitro agonist potency · Greater food intake reduction in vivo (IT and SC routes) · 3 FDA-approved melanocortin drugs referenced","methodology":"Researchers synthesized macrocyclic melanocortin peptide agonists with 0 to 3 extracyclic arginine residues attached via a branching lysine. In vitro activity was tested at mouse melanocortin receptors. Two compounds — the parent macrocycle and the 3-arginine derivative — were then tested in vivo in mice for food intake reduction via intrathecal and subcutaneous injection.","limitations":"This is an animal study using mice — human pharmacokinetics and efficacy could differ substantially. The specific food intake reduction data points were not provided in the abstract. The mechanism by which extracyclic arginines enhance in vivo efficacy (possibly cell penetration or bioavailability) was not conclusively determined. Only a limited number of variants were tested in vivo."},{"rthcId":"RPEP-08165","title":"Amylin, Another Important Neuroendocrine Hormone for the Treatment of Diabesity.","authors":"Eržen, Stjepan; Tonin, Gašper; Jurišić Eržen, Dubravka; Klen, Jasna","year":2024,"journal":"International journal of molecular sciences, 25(3)","doi":"10.3390/ijms25031517","pmid":"38338796","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08166","title":"Fremanezumab-associated injection site alopecia.","authors":"Esguerra, Mark; Engel, Emily Rubenstein","year":2024,"journal":"BMJ case reports, 17(8)","doi":"10.1136/bcr-2024-260741","pmid":"39134332","tags":[],"studyType":"case-report","evidenceStrength":"low","keyFinding":"A patient using fremanezumab (a CGRP-blocking antibody for migraine prevention) developed persistent hair loss localized to the injection site on the lower extremity. This is notable because most reported CGRP inhibitor-related alopecia has been scalp-based and associated with erenumab, not fremanezumab.\n\nThe proposed mechanism is that blocking CGRP removes its immunomodulatory protection of hair follicles, causing the follicle's 'immune privilege' to collapse — essentially, the immune system attacks hair follicles that were previously shielded by CGRP signaling.","whyItMatters":"CGRP inhibitors are rapidly becoming first-line migraine prevention drugs, prescribed to millions of patients. While clinical trials showed few side effects, post-marketing reports of hair loss are accumulating. This case adds injection site-specific alopecia to the known pattern and proposes a mechanistic explanation rooted in CGRP's role in hair follicle immune privilege — important for understanding why this peptide-blocking therapy affects hair growth.","specificNumbers":"1 patient · Fremanezumab injection · Lower extremity injection site · Persistent localized alopecia","methodology":"This is a clinical case report documenting a single patient in a headache clinic who developed persistent localized alopecia at the fremanezumab injection site on the lower extremity. The authors reviewed the clinical presentation, medication history, and existing literature on CGRP inhibitor-associated alopecia to propose a mechanism.","limitations":"As a single case report, this cannot establish causation — the alopecia could be coincidental. No biopsy was described to confirm the proposed immune privilege mechanism. The rarity of injection site-specific alopecia makes it difficult to determine incidence rates or risk factors."},{"rthcId":"RPEP-08167","title":"Safety and efficacy of glucagon-like peptide-1 (GLP-1) receptor agonists in patients with weight regain or insufficient weight loss after metabolic bariatric surgery: A systematic review and meta-analysis.","authors":"Esparham, Ali; Mehri, Ali; Dalili, Amin; Richards, Jesse; Khorgami, Zhamak","year":2024,"journal":"Obesity reviews : an official journal of the International Association for the Study of Obesity, 25(11), e13811","doi":"10.1111/obr.13811","pmid":"39134066","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08168","title":"Glucagon-Like Peptide-1 Receptor Agonists and Thyroid Cancer: A Narrative Review.","authors":"Espinosa De Ycaza, Ana E; Brito, Juan P; McCoy, Rozalina G; Shao, Hui; Singh Ospina, Naykky","year":2024,"journal":"Thyroid : official journal of the American Thyroid Association, 34(4), 403-418","doi":"10.1089/thy.2023.0530","pmid":"38343381","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Despite a black box warning based on rodent studies showing a link between GLP-1 receptor agonists and medullary thyroid cancer (MTC), this narrative review finds no conclusive evidence of elevated thyroid cancer risk in humans. Randomized controlled trials show thyroid cancer is rare in GLP-1 RA users, with imprecise effect estimates that do not consistently demonstrate increased risk. Observational studies yield inconsistent results. While pharmacovigilance databases show increased thyroid cancer reporting, these studies cannot establish causation. The biological plausibility for MTC in rodents does not clearly extend to non-MTC thyroid cancer in humans.","whyItMatters":"The thyroid cancer black box warning on GLP-1 receptor agonists like semaglutide and liraglutide has caused significant patient anxiety and may be leading to underuse of these highly effective medications. This review helps clinicians and patients put the risk in perspective: while the warning is based on real rodent data, human evidence does not support a clear thyroid cancer link. Unwarranted fear could also lead to unnecessary thyroid screening and overdiagnosis.","specificNumbers":"Review of RCTs, observational studies, and pharmacovigilance data · thyroid cancer is rare across all study types · effect estimates imprecise · no consistent evidence of increased risk","methodology":"This is a narrative review that synthesizes evidence across four categories: basic/translational research on biological plausibility, randomized controlled trials, observational studies with real-world outcomes, and pharmacovigilance (postmarketing safety) databases. Each evidence type is evaluated for its strengths and limitations in addressing the GLP-1 RA–thyroid cancer question.","limitations":"As a narrative review, the evidence synthesis is qualitative rather than quantitative. The low frequency of thyroid cancer events in clinical trials makes it difficult to definitively rule out small risk increases. Observational studies have inherent biases including inconsistent outcome definitions. Pharmacovigilance data reflect reporting patterns rather than true incidence rates."},{"rthcId":"RPEP-08169","title":"Comparative Effects of GLP-1 Agonists, Sleeve Gastrectomy and Roux-en-Y Gastric Bypass on Diabetes Mellitus Outcomes.","authors":"Essop, Tasiyah; Tran, Kyle; Purdy, Amanda C; Daly, Shaun C","year":2024,"journal":"Current diabetes reports, 24(12), 273-289","doi":"10.1007/s11892-024-01554-2","pmid":"39325334","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08170","title":"A survey of stapling methods to increase affinity, activity, and stability of ghrelin analogues.","authors":"Esteban, Juan J; Mason, Julia R; Kaminski, Jakob; Ramachandran, Rithwik; Luyt, Leonard G","year":2024,"journal":"RSC medicinal chemistry, 15(1), 254-266","doi":"10.1039/d3md00441d","pmid":"38283230","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08171","title":"Incretin Hormone Secretion in Women with Polycystic Ovary Syndrome: Roles of Obesity, Insulin Sensitivity and Treatment with Metformin and GLP-1s.","authors":"Etrusco, Andrea; Mikuš, Mislav; D'Amato, Antonio; Barra, Fabio; Planinić, Petar; Goluža, Trpimir; Buzzaccarini, Giovanni; Marušić, Jelena; Tešanović, Mara; Laganà, Antonio Simone","year":2024,"journal":"Biomedicines, 12(3)","doi":"10.3390/biomedicines12030653","pmid":"38540265","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08172","title":"Thymosin β4 and β10 Expression in Human Organs during Development: A Review.","authors":"Faa, Gavino; Messana, Irene; Coni, Pierpaolo; Piras, Monica; Pichiri, Giuseppina; Piludu, Marco; Iavarone, Federica; Desiderio, Claudia; Vento, Giovanni; Tirone, Chiara; Manconi, Barbara; Olianas, Alessandra; Contini, Cristina; Cabras, Tiziana; Castagnola, Massimo","year":2024,"journal":"Cells, 13(13)","doi":"10.3390/cells13131115","pmid":"38994967","tags":[],"studyType":"review","evidenceStrength":"review","keyFinding":"This review maps how thymosin β4 and thymosin β10 are expressed across human organs throughout development — from fetal stages through different ages after birth. The research group used proteomics (on preterm newborn saliva and gingival fluid) and immunohistochemistry (on autopsy tissues from fetuses and adults) to track these two peptides over time and across tissues.\n\nKey discoveries include that β-thymosins are expressed in organ-specific and age-dependent patterns, with important implications for understanding their roles in development and disease. The review addresses the 'β-thymosin enigma' — the puzzle of how these small, seemingly simple peptides can have such diverse biological functions across so many tissues, including roles in carcinogenesis.","whyItMatters":"Thymosin β4 is one of the most studied peptides in regenerative medicine, yet its fundamental biology during human development remains poorly mapped. Understanding when and where β-thymosins are expressed during organ formation helps explain both their therapeutic potential and their involvement in diseases like cancer. The developmental expression patterns could reveal new therapeutic windows and targets.","specificNumbers":"Thymosin β4 and β10 studied · Multiple human organs and tissues · Fetal through adult ages · Proteomics + immunohistochemistry methods · Preterm newborn saliva studied · Autopsy tissue analysis","methodology":"The review summarizes the group's multi-year research program using two approaches: (1) proteomics analysis of saliva from preterm newborns and gingival crevicular fluid to identify β-thymosin expression, and (2) immunohistochemistry on autopsy tissues from human fetuses at different gestational ages and adults to map β-thymosin distribution across organs.","limitations":"The review primarily summarizes work from a single research group, which may reflect a particular methodological perspective. Autopsy tissues may not perfectly represent in vivo expression due to post-mortem changes. The abstract doesn't detail which specific organs were studied or provide quantitative expression data. Immunohistochemistry detects protein presence but doesn't precisely quantify levels."},{"rthcId":"RPEP-08173","title":"Determining the expression of vitamin D receptor, regulator of iron metabolism hepcidin and cathelicidin antimicrobial peptide genes for development of future diagnostic and therapeutic options in patients with inflammatory bowel disease.","authors":"Fabisiak, N; Tarasiuk-Zawadzka, A; Fabisiak, A; Wlodarczyk, M; Fichna, J","year":2024,"journal":"Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 75(4)","doi":"10.26402/jpp.2024.4.06","pmid":"39415526","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08174","title":"A peptide-based pH-sensitive antibacterial hydrogel for healing drug-resistant biofilm-infected diabetic wounds.","authors":"Fan, Duoyang; Xie, Ruyan; Liu, Xiaohui; Li, Haohan; Luo, Ziheng; Li, Yanbing; Chen, Fei; Zeng, Wenbin","year":2024,"journal":"Journal of materials chemistry. B, 12(22), 5525-5534","doi":"10.1039/d4tb00594e","pmid":"38746970","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The COA-T3 hydrogel, composed of quaternized chitosan and oxidized dextran, successfully co-delivered the antimicrobial peptide HHC10 and the photosensitizer TPI-PN via pH-sensitive release. In vitro, the hydrogel showed remarkable activity against drug-resistant bacteria. In vivo, it significantly promoted healing of infected diabetic wounds in mice.\n\nThe dual mechanism — antimicrobial peptide killing combined with photodynamic therapy — provided enhanced antibacterial activity compared to either approach alone. The pH-responsive release ensured both agents were delivered specifically at the infected wound site. The hydrogel also demonstrated excellent biocompatibility, supporting its potential as a wound dressing material.","whyItMatters":"Diabetic foot ulcers are a leading cause of amputation, and antibiotic-resistant biofilm infections make them even harder to treat. This hydrogel addresses multiple challenges simultaneously: it kills drug-resistant bacteria through two independent mechanisms (peptide + phototherapy), releases its cargo specifically at the infection site via pH sensing, and provides a moist wound environment that supports healing. This multi-functional approach could offer a significant advancement over current wound dressings.","specificNumbers":"","methodology":"Researchers synthesized COA-T3 hydrogel from quaternized chitosan and oxidized dextran, incorporating the antimicrobial peptide HHC10 and photosensitizer TPI-PN via covalent coupling. pH-sensitive release was characterized in vitro. Antibacterial activity was tested against drug-resistant bacteria and biofilms. Biocompatibility was assessed. In vivo wound healing was evaluated in a diabetic mouse model with infected wounds.","limitations":"This was a preclinical study using a diabetic mouse wound model, which does not fully replicate the complexity of human diabetic foot ulcers (which involve deeper tissue, variable blood flow, and neuropathy). The specific drug-resistant bacterial strains tested were not detailed in the abstract. The photodynamic component requires external light exposure, which may be impractical for some wound locations. Long-term safety, shelf stability, and manufacturing scalability of the hydrogel are not addressed. Cost-effectiveness compared to existing wound care has not been evaluated."},{"rthcId":"RPEP-08175","title":"Harnessing antimicrobial peptide-coupled photosensitizer to combat drug-resistant biofilm infections through enhanced photodynamic therapy.","authors":"Fan, Duoyang; Liu, Xiaohui; Ren, Yueming; Luo, Ziheng; Li, Yanbing; Dong, Jie; Wegner, Seraphine V; Chen, Fei; Zeng, Wenbin","year":2024,"journal":"Acta pharmaceutica Sinica. B, 14(4), 1759-1771","doi":"10.1016/j.apsb.2023.12.016","pmid":"38572100","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The antimicrobial peptide KRWWKWIRW (identified through artificial neural network screening) was coupled with an aggregation-induced emission (AIE) photosensitizer. The conjugate demonstrated:\n\n- Excellent killing of both gram-positive (G+) and gram-negative (G-) bacteria in vitro\n- Significant destruction of MRSA biofilms\n- Enhanced photoactivatable antibacterial activity against G- bacteria through bacterial aggregation\n- Remarkable efficacy in treating wound infections in mice in vivo\n\nThe AIE photosensitizer fluoresces more brightly when aggregated, enabling visualization of the antibacterial mechanism in action.","whyItMatters":"Bacterial biofilms cause 80% of chronic infections and are 1,000 times more resistant to antibiotics than free-floating bacteria. This dual-action approach — combining a membrane-targeting peptide with light-activated killing — offers a new strategy against the most treatment-resistant infections, including MRSA biofilms in wounds that often lead to amputation or life-threatening sepsis.","specificNumbers":"","methodology":"An antimicrobial peptide (KRWWKWIRW) was identified through artificial neural network screening and chemically coupled to an aggregation-induced emission (AIE) photosensitizer. The conjugate was tested in vitro against gram-positive and gram-negative bacteria for direct killing and biofilm destruction. MRSA biofilms were specifically targeted. In vivo wound infection treatment was assessed in a mouse model under photodynamic therapy conditions (light exposure).","limitations":"The study is preclinical, with in vivo testing limited to a mouse wound infection model. Photodynamic therapy requires light exposure, which limits use to surface-accessible infections (wounds, skin) rather than deep-seated infections. The long-term stability, toxicity profile, and manufacturing scalability of the conjugate were not detailed. Clinical translation would require significant further development."},{"rthcId":"RPEP-08176","title":"KGRT peptide incorporated hydrogel with antibacterial activity for wound healing by optimizing cellular functions via ERK/eNOS signaling.","authors":"Fan, Limin; Shen, Fang; Wu, Dequn; Ren, Tianbin; Jiang, Wencheng","year":2024,"journal":"International journal of biological macromolecules, 265(Pt 1), 130781","doi":"10.1016/j.ijbiomac.2024.130781","pmid":"38492691","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08177","title":"The deuterated pyrazoloquinolinone targeting α6 subunit-containing GABAA receptor as novel candidate for inhibition of trigeminovascular system activation: implication for migraine therapy.","authors":"Fan, Pi-Chuan; Chiou, Lih-Chu; Lai, Tzu-Hsuan; Sharmin, Dishary; Cook, James; Lee, Ming Tatt","year":2024,"journal":"Frontiers in pharmacology, 15, 1451634","doi":"10.3389/fphar.2024.1451634","pmid":"39253381","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"DK-I-56-1 (a deuterated α6GABAAR-selective positive allosteric modulator) significantly reduced three markers of trigeminovascular system activation in a capsaicin-induced migraine model:\n\n- TCC neuronal activation (c-Fos immunoreactivity)\n- Trigeminal ganglion CGRP immunoreactivity elevation\n- Dural CGRP depletion (indicating reduced CGRP release)\n\nAt 3 mg/kg, DK-I-56-1 was comparable in efficacy to 30 mg/kg topiramate. The effect was blocked by furosemide (a blood-brain-barrier impermeable α6GABAAR antagonist), confirming the drug works through peripheral GABA receptors, not central ones. Oral administration was also effective.","whyItMatters":"Anti-CGRP antibodies and receptor blockers have transformed migraine treatment, but they are expensive injectable biologics. This study reveals a completely different strategy — reducing CGRP release upstream by modulating GABA receptors in the trigeminal ganglion. If successful in humans, this oral small molecule approach could provide an affordable alternative that achieves the same CGRP-reducing endpoint through a novel mechanism.","specificNumbers":"","methodology":"Male Wistar rats received intra-cisternal capsaicin to activate the trigeminovascular system (mimicking migraine). DK-I-56-1 and RV-I-29 were administered intraperitoneally. Outcomes measured: c-Fos-immunoreactive neurons in the trigeminal cervical complex (central sensitization), CGRP immunoreactivity in trigeminal ganglia (peripheral activation), and dural CGRP levels (neuropeptide release). Furosemide was used to confirm peripheral mechanism. Oral dosing was also tested.","limitations":"This is a preclinical rat study — efficacy and safety in humans are unknown. The capsaicin model mimics some aspects of migraine but does not fully replicate human migraine pathophysiology. The long-term effects of chronic α6GABAAR modulation on trigeminal function are unknown. Side effects were not systematically assessed. The deuterated modifications improve half-life but the clinical pharmacokinetics remain to be characterized."},{"rthcId":"RPEP-08178","title":"Effects of GLP-1 receptor agonists on the degree of liver fibrosis and CRP in non-alcoholic fatty liver disease and non-alcoholic steatohepatitis: A systematic review and meta-analysis.","authors":"Fang, Lixuan; Li, Jine; Zeng, Haixia; Liu, Jianping","year":2024,"journal":"Primary care diabetes, 18(3), 268-276","doi":"10.1016/j.pcd.2024.03.005","pmid":"38555202","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08179","title":"Observational Study of Trans-Septal Endocardial Left Ventricle Lead Implant for Effective Cardiac Resynchronization Therapy in Patients with Heart Failure and Challenging Coronary Sinus Anatomy.","authors":"Farhangee, Arsalan; Davies, Mark J; Gaughan, Katie; Mesina, Mihai; Mîndrilă, Ion","year":2024,"journal":"Biomedicines, 12(12)","doi":"10.3390/biomedicines12122693","pmid":"39767600","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08180","title":"Upgrading Mitochondria-Targeting Peptide-Based Nanocomplexes for Zebrafish In Vivo Compatibility Assays.","authors":"Faria, Rúben; Vivès, Eric; Boisguérin, Prisca; Descamps, Simon; Sousa, Ângela; Costa, Diana","year":2024,"journal":"Pharmaceutics, 16(7)","doi":"10.3390/pharmaceutics16070961","pmid":"39065658","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08181","title":"Membrane Permeability in a Large Macrocyclic Peptide Driven by a Saddle-Shaped Conformation.","authors":"Faris, Justin H; Adaligil, Emel; Popovych, Nataliya; Ono, Satoshi; Takahashi, Mifune; Nguyen, Huy; Plise, Emile; Taechalertpaisarn, Jaru; Lee, Hsiau-Wei; Koehler, Michael F T; Cunningham, Christian N; Lokey, R Scott","year":2024,"journal":"Journal of the American Chemical Society, 146(7), 4582-4591","doi":"10.1021/jacs.3c10949","pmid":"38330910","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08182","title":"Anti-IL-1RAP scFv-mSA-S19-TAT fusion carrier as a multifunctional platform for versatile delivery of biotinylated payloads to myeloid leukemia cells.","authors":"Farokhi-Fard, Aref; Rahmati, Saman; Hashemi Aval, Negin Sadat; Barkhordari, Farzaneh; Bayat, Elham; Komijani, Samira; Aghamirza Moghim Aliabadi, Hooman; Davami, Fatemeh","year":2024,"journal":"Scientific reports, 14(1), 25080","doi":"10.1038/s41598-024-76851-7","pmid":"39443595","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08183","title":"Portal vein thrombosis in a patient on semaglutide.","authors":"Farooqi, Mohammed F; Khan, Maria; Muhammad, Arshad M; Agha, Adnan","year":2024,"journal":"Qatar medical journal, 2024(4), 75","doi":"10.5339/qmj.2024.75","pmid":"39925824","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08184","title":"Extensive Deep Vein Thrombosis in a Young Man Taking Tirzepatide for Weight Loss.","authors":"Farooqi, Mohammed Fareeduddin; Mehmood, Muhammad Arshad; Khan, Maria; Salman, Hafiz Muhammad; Agha, Adnan","year":2024,"journal":"AACE clinical case reports, 10(6), 261-263","doi":"10.1016/j.aace.2024.08.011","pmid":"39734498","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08185","title":"Tunable Macroscopic Alignment of Self-Assembling Peptide Nanofibers.","authors":"Farsheed, Adam C; Zevallos-Delgado, Christian; Yu, Le Tracy; Saeidifard, Sajede; Swain, Joseph W R; Makhoul, Jonathan T; Thomas, Adam J; Cole, Carson C; Garcia Huitron, Eric; Grande-Allen, Kathryn Jane; Singh, Manmohan; Larin, Kirill V; Hartgerink, Jeffrey D","year":2024,"journal":"ACS nano, 18(19), 12477-12488","doi":"10.1021/acsnano.4c02030","pmid":"38699877","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08186","title":"Tunable Macroscopic Alignment of Self-Assembling Peptide Nanofibers.","authors":"Farsheed, Adam C; Zevallos-Delgado, Christian; Yu, Le Tracy; Saeidifard, Sajede; Swain, Joseph W R; Makhoul, Jonathan T; Thomas, Adam J; Cole, Carson C; Huitron, Eric Garcia; Grande-Allen, K Jane; Singh, Manmohan; Larin, Kirill V; Hartgerink, Jeffrey D","year":2024,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2024.02.02.578651","pmid":"38352501","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Researchers developed a simple extrusion-based method to create aligned peptide nanofiber hydrogels by applying shear force during ion-triggered gelation. By adjusting phosphate buffer concentration during self-assembly, they could tune the degree of fiber alignment and packing. More aligned hydrogels were stronger and stiffer under hydrated conditions.\n\nWhen cells were grown on these scaffolds, aligned nanofibers guided directional cell spreading, but — surprisingly — increased matrix alignment did not always lead to increased cellular alignment. Nanoscale analysis revealed that cells need mechanical coupling to interpret alignment cues, not just structural alignment alone.","whyItMatters":"Many tissues in the body — including tendons, heart muscle, and nerve — have highly organized, aligned structures that give them directional strength. Recreating this alignment in lab-grown tissue scaffolds has been a major challenge. This peptide-based approach provides a tunable, scalable method to create aligned scaffolds that mimic natural tissue structure, while also revealing that simply aligning fibers isn't enough — cells must be mechanically coupled to the scaffold to respond to its structure.","specificNumbers":"Tunable alignment via phosphate buffer concentration · Enhanced strength and stiffness with alignment · Multiple cell types tested · Gradient of anisotropy achieved · Extrusion-based fabrication","methodology":"Self-assembling peptides were extruded through a nozzle while simultaneously triggering gelation with ion-containing buffer. Shear forces during extrusion aligned the nanofibers, and the alignment was kinetically trapped by gelation. Phosphate buffer concentration was varied to tune alignment. Mechanical properties were tested via rheology under hydrated conditions. Cell behavior was assessed by seeding multiple cell types on scaffolds with varying alignment and measuring directional spreading. Nanoscale cell-matrix interactions were imaged.","limitations":"This is a preprint (bioRxiv), not yet peer-reviewed. The study focused on in vitro characterization and cell behavior — no in vivo implantation or tissue formation was tested. The finding that increased alignment doesn't always improve cell response adds complexity to scaffold design. Long-term scaffold stability and degradation properties were not characterized in the abstract."},{"rthcId":"RPEP-08187","title":"Use of liraglutide after bariatric surgery: a 36-month follow-up in a real-world setting in Chile.","authors":"Farías, María Magdalena","year":2024,"journal":"Archives of endocrinology and metabolism, 68, e230234","doi":"10.20945/2359-4292-2023-0234","pmid":"39420938","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08188","title":"Efficacy of Different Doses and Forms of the GLP-1 Receptor Agonist Semaglutide in Weight Reduction Among Non-diabetic Obese or Overweight Populations.","authors":"Fatima, Nazeefa; Anand, Abhinav; Palvia, Aadi R; Kaur, Avneet; Azeez, Gibran A; Thirunagari, Mounika; Butt, Samia Rauf R","year":2024,"journal":"Cureus, 16(9), e68786","doi":"10.7759/cureus.68786","pmid":"39376859","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 10 studies (9 RCTs and 1 retrospective cohort) encompassing 6,623 non-diabetic overweight or obese participants, semaglutide in various doses and forms demonstrated consistent, significant weight loss effects. The review examined changes in body weight, waist circumference, and the proportion of patients achieving at least 5% clinically meaningful weight loss. The consolidated evidence endorsed semaglutide as a highly efficient weight-reducing agent in people without diabetes.","whyItMatters":"Most early GLP-1 RA research focused on diabetes patients, where weight loss was initially considered a side benefit. This systematic review consolidates the evidence specifically for non-diabetic populations — the primary market for drugs like Wegovy. By pooling results from 6,623 participants across high-quality studies, it provides a comprehensive evidence base supporting semaglutide's use purely as a weight loss treatment.","specificNumbers":"10 studies · 9 RCTs + 1 retrospective cohort · 6,623 participants · Non-diabetic population · Endpoints: weight change, waist circumference, ≥5% weight loss achievement","methodology":"Systematic review following PRISMA 2020 guidelines. Three databases searched (PubMed, PubMed Central, Cochrane Library) with 423 initial papers narrowed to 10 high-quality studies published in the last 5 years. Studies were filtered using inclusion/exclusion criteria and quality appraisal tools. Included studies compared semaglutide at various doses and forms to placebo or active comparators in non-diabetic overweight/obese adults.","limitations":"This is a systematic review without meta-analysis — the results are described qualitatively rather than pooled statistically. Published in Cureus (a lower-impact journal), and the abstract doesn't report specific weight loss numbers, making it difficult to assess the magnitude of effects. The review's conclusion is broad ('highly efficient') without distinguishing between dose-specific outcomes. Only studies from the last 5 years were included, potentially missing earlier relevant data."},{"rthcId":"RPEP-08189","title":"Nociceptor-to-macrophage communication through CGRP/RAMP1 signaling drives endometriosis-associated pain and lesion growth in mice.","authors":"Fattori, Victor; Zaninelli, Tiago H; Rasquel-Oliveira, Fernanda S; Heintz, Olivia K; Jain, Ashish; Sun, Liang; Seshan, Maya L; Peterse, Daniëlle; Lindholm, Anne E; Anchan, Raymond M; Verri, Waldiceu A; Rogers, Michael S","year":2024,"journal":"Science translational medicine, 16(772), eadk8230","doi":"10.1126/scitranslmed.adk8230","pmid":"39504351","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08190","title":"A randomized, double-blind, placebo-controlled study of a GHSR blocker in people with alcohol use disorder.","authors":"Faulkner, Monica L; Farokhnia, Mehdi; Lee, Mary R; Farinelli, Lisa; Browning, Brittney D; Abshire, Kelly; Daurio, Allison M; Munjal, Vikas; Deschaine, Sara L; Boukabara, Selim R; Fortney, Christopher; Sherman, Garrick; Schwandt, Melanie; Akhlaghi, Fatemeh; Momenan, Reza; Ross, Thomas J; Persky, Susan; Leggio, Lorenzo","year":2024,"journal":"JCI insight, 9(24)","doi":"10.1172/jci.insight.182331","pmid":"39704175","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In this Phase IIa randomized, double-blind, placebo-controlled, within-subject crossover study of 42 individuals with alcohol use disorder (29 completers):\n\n- PF-5190457 (100 mg twice daily) did NOT reduce cue-elicited alcohol craving during a bar-like laboratory experiment\n- PF-5190457 did NOT influence neural activation during a cue-reactivity task in the fMRI subset (n=12)\n- PF-5190457 DID reduce virtual calories selected in a cafeteria-like virtual reality environment (P=0.04)\n\nThe primary hypothesis — that blocking the ghrelin receptor would reduce alcohol craving — was not supported. However, the food-related finding provides human evidence that GHSR blockade influences caloric intake decisions.","whyItMatters":"Alcohol use disorder is a major public health problem with limited pharmacological treatments. The ghrelin system has been a promising therapeutic target based on strong animal evidence. While this trial's negative result for alcohol craving is disappointing, it provides crucial human data that narrows the path forward — either the ghrelin system's role in human alcohol behavior differs from animal models, or different approaches to targeting it may be needed. The positive food-related finding also highlights the ghrelin-appetite connection as a viable therapeutic direction.","specificNumbers":"","methodology":"This was a randomized, double-blind, placebo-controlled, within-subject crossover study. Forty-two individuals with alcohol use disorder received PF-5190457 100 mg twice daily or placebo in two counterbalanced stages. Assessments included: (1) an alcohol cue-reactivity experiment in a bar-like laboratory setting measuring craving; (2) a virtual food choice experiment in a cafeteria-like virtual reality environment measuring calorie selection; and (3) for a subset of 12 participants, a cue-reactivity task during functional MRI to measure brain activation patterns. The trial was registered on ClinicalTrials.gov (NCT02707055).","limitations":"The sample size was modest (42 enrolled, only 29 completers), limiting statistical power to detect smaller effects. The within-subject crossover design, while reducing individual variability, may introduce carryover effects. The fMRI subset was very small (n=12). Cue-reactivity in a laboratory setting may not reflect real-world alcohol craving or consumption. The study measured craving rather than actual drinking behavior. PF-5190457 is an inverse agonist/competitive antagonist — different ghrelin receptor targeting strategies might yield different results."},{"rthcId":"RPEP-08191","title":"Brainstem BDNF neurons are downstream of GFRAL/GLP1R signalling.","authors":"Feetham, Claire H; Collabolletta, Valeria; Worth, Amy A; Shoop, Rosemary; Groom, Sam; Harding, Court; Boutagouga Boudjadja, Mehdi; Coskun, Tamer; Emmerson, Paul J; D'Agostino, Giuseppe; Luckman, Simon M","year":2024,"journal":"Nature communications, 15(1), 10749","doi":"10.1038/s41467-024-54367-y","pmid":"39737892","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08192","title":"Effects of semaglutide on gut microbiota, cognitive function and inflammation in obese mice.","authors":"Feng, Jing; Teng, Zhenjie; Yang, Yu; Liu, Jingzhen; Chen, Shuchun","year":2024,"journal":"PeerJ, 12, e17891","doi":"10.7717/peerj.17891","pmid":"39148685","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In obese mice fed a high-fat diet for 12 weeks then treated with semaglutide:\n\n- Cognitive function improved significantly on the Morris water maze test\n- Pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) were reduced\n- Gut microbiota changes were reversed: Akkermansia, Muribaculaceae, Coriobacteriaceae_UCG_002, and Clostridia_UCG_014 (all decreased by obesity) were restored; Romboutsia, Dubosiella, and Enterorhabdus (increased by obesity) were reduced\n\nCorrelation analysis revealed:\n- Muribaculaceae and Clostridia_UCG_014 positively correlated with cognitive function\n- Romboutsia and Dubosiella negatively correlated with cognitive function\n- Romboutsia positively correlated with inflammatory cytokines (TNF-α, IL-6, IL-1β)\n- Clostridia_UCG_014 negatively correlated with inflammatory cytokines","whyItMatters":"With millions of people now taking semaglutide for diabetes and obesity, understanding how it affects the brain is critically important. This study provides mechanistic evidence that semaglutide's cognitive benefits may operate through the gut-brain axis — by restoring healthy gut bacteria and reducing inflammation. This could help explain the emerging clinical observations that GLP-1 medications appear to protect against dementia and cognitive decline.","specificNumbers":"","methodology":"Twenty-four C57BL/6J male mice were divided into three groups of 8: normal-chow diet (NCD), high-fat diet (HFD), and HFD + semaglutide (Sema). After establishing obesity with HFD, mice received semaglutide or saline for 12 weeks. Cognitive function was assessed with the Morris water maze test. Serum pro-inflammatory cytokines were measured. Gut microbiota composition was analyzed using 16S rRNA gene sequencing. Correlation analysis linked microbiota changes to cognitive and inflammatory outcomes.","limitations":"This is an animal study with a small sample size (8 mice per group), which limits statistical power and generalizability. Mouse gut microbiota and cognitive processes differ from humans. The Morris water maze tests spatial memory specifically and does not capture the full range of cognitive functions. Correlation between microbiota and outcomes does not prove causation — the bacteria may be bystanders rather than drivers. The 12-week timeframe may not reflect long-term effects. No dose-response analysis was performed."},{"rthcId":"RPEP-08193","title":"HOXD9/APOC1 axis promotes macrophage M1 polarization to exacerbate diabetic kidney disease progression through activating NF-κB signaling pathway.","authors":"Feng, Ya; Zhang, Yalan; Gao, Fang; Liu, Miaomiao; Luo, Yangyan","year":2024,"journal":"Hereditas, 161(1), 40","doi":"10.1186/s41065-024-00345-9","pmid":"39511608","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08194","title":"Real-world effectiveness and safety of erenumab for the treatment of migraine: A systematic review and meta-analysis.","authors":"Fernández-Bravo-Rodrigo, Jaime; Cavero-Redondo, Iván; Lucerón-Lucas-Torres, Maribel; Martínez-García, Irene; Flor-García, Amparo; Barreda-Hernández, Dolores; Pascual-Morena, Carlos","year":2024,"journal":"European journal of pharmacology, 976, 176702","doi":"10.1016/j.ejphar.2024.176702","pmid":"38823758","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 53 real-world studies, erenumab reduced monthly migraine days by 7.18 days and monthly headache days by 6.89 days at 3 months. HIT-6 disability scores improved by 6.97 points, medication use dropped by 6.22 days/month, and pain intensity decreased by 1.71 points. Effects increased slightly at 6 and 12 months. Approximately one-third of patients achieved >30% response, one-sixth achieved >50% response, and 3–4% became completely migraine-free. Adverse event rates were 0.34 at 6 months and 0.43 at 12 months.","whyItMatters":"Clinical trials of erenumab used strict selection criteria, leaving questions about real-world performance. This first real-world meta-analysis of 53 studies confirms that erenumab delivers clinically meaningful migraine reduction outside controlled trial settings, validating CGRP pathway targeting as an effective approach for the broader migraine population.","specificNumbers":"53 studies · MMD reduction -7.18 days · MHD reduction -6.89 days · HIT-6 improvement -6.97 · medication days -6.22 · ~33% achieved >30% response · ~17% achieved >50% response · 3-4% complete response · AE rate 0.34–0.43","methodology":"Systematic review and meta-analysis. Databases searched: PubMed, Scopus, Web of Science, and Cochrane Library from inception to December 2023. Studies reporting real-world erenumab outcomes were included. Meta-analyses of proportions or mean differences were performed for multiple endpoints at 3, 6, and 12 months.","limitations":"Included studies are observational real-world data without control groups, so placebo effects cannot be excluded. Heterogeneity across 53 studies in patient populations, dosing protocols, and outcome definitions may affect pooled estimates. Publication bias may favor positive results."},{"rthcId":"RPEP-08195","title":"Development of a Neuropeptide Y-Sensitive Implantable Microelectrode for Continuous Measurements.","authors":"Fernández-Vega, Lauren; Meléndez-Rodríguez, Dorian Enid; Ospina-Alejandro, Mónica; Casanova, Karina; Vázquez, Yolimar; Cunci, Lisandro","year":2024,"journal":"ACS sensors, 9(5), 2645-2652","doi":"10.1021/acssensors.4c00449","pmid":"38709872","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08196","title":"Heterobivalent Dual-Target Peptide for Integrin-αvβ3 and Neuropeptide Y Receptors on Breast Tumor.","authors":"Ferreira, Aryel H; Real, Caroline C; Malafaia, Osvaldo","year":2024,"journal":"Pharmaceuticals (Basel, Switzerland), 17(10)","doi":"10.3390/ph17101328","pmid":"39458969","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08197","title":"GHSR signalling in perinatal phases is involved in liver metabolism at puberty.","authors":"Ferreira-Junior, Marcos Divino; Cavalcante, Keilah Valéria Naves; Xavier, Carlos Henrique; Vanzela, Emerielle Cristine; Boschero, Antonio Carlos; Matafome, Paulo; Gomes, Rodrigo Mello","year":2024,"journal":"The Journal of endocrinology, 263(1)","doi":"10.1530/JOE-24-0039","pmid":"39045853","tags":[],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Blocking ghrelin receptor (GHSR) signaling during the perinatal period with LEAP2 (a natural ghrelin-blocking peptide) altered liver metabolism and glucose regulation in rats at puberty. LEAP2 injections during pregnancy or early postnatal life significantly impacted liver PEPCK expression — a key enzyme in glucose production — and affected glucose homeostasis in a sex- and timing-dependent manner.\n\nImportantly, these metabolic effects occurred without changes in body weight or food intake, suggesting that early-life ghrelin signaling programs metabolic function in ways that only become apparent later in development. The authors note these effects may be the beginning of larger metabolic imbalances that could emerge in adulthood.","whyItMatters":"LEAP2 has emerged as ghrelin's natural 'off switch' — a peptide that blocks ghrelin's effects. This study reveals that disrupting ghrelin signaling during critical developmental windows with LEAP2 has lasting metabolic consequences, particularly in the liver. This matters for understanding how early-life peptide signaling programs lifelong metabolic health, and raises questions about whether interventions targeting the ghrelin system (including MK-677, a popular growth hormone secretagogue) could have unintended developmental effects if used during pregnancy or infancy.","specificNumbers":"LEAP2[1-14] fragment used · 2 experimental models (pregnancy + postnatal) · MK-677 used as comparator · liver PEPCK expression significantly altered · sex-dependent glucose effects · no weight or food intake changes","methodology":"Animal study using two rat models: (1) LEAP2[1-14] peptide injections in pregnant female rats, and (2) postnatal modulation of ghrelin receptors with either LEAP2[1-14] or MK-677 in offspring. Researchers measured body weight, food intake, glucose homeostasis, and liver enzyme expression (PEPCK) in the offspring at puberty.","limitations":"Rat model — early-life metabolic programming may differ between species. The study used a truncated LEAP2 fragment [1-14] rather than full-length LEAP2. Effects at puberty were described as 'not expressive' — suggesting they may be subtle early signals rather than robust findings. Adult outcomes were not assessed. Specific glucose homeostasis data and effect sizes were not detailed in the abstract."},{"rthcId":"RPEP-08198","title":"All GLP-1 Agonists Should, Theoretically, Cure Alzheimer's Dementia but Dulaglutide Might Be More Effective Than the Others.","authors":"Fessel, Jeffrey","year":2024,"journal":"Journal of clinical medicine, 13(13)","doi":"10.3390/jcm13133729","pmid":"38999294","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08199","title":"Glucagon-like peptide-1 receptor agonists and risk of gastrointestinal cancers: A systematic review and meta-analysis of randomized controlled trials.","authors":"Figlioli, Gisella; Piovani, Daniele; Peppas, Spyros; Pugliese, Nicola; Hassan, Cesare; Repici, Alessandro; Lleo, Ana; Aghemo, Alessio; Bonovas, Stefanos","year":2024,"journal":"Pharmacological research, 208, 107401","doi":"10.1016/j.phrs.2024.107401","pmid":"39251099","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08200","title":"The TRPA1 Ion Channel Mediates Oxidative Stress-Related Migraine Pathogenesis.","authors":"Fila, Michal; Przyslo, Lukasz; Derwich, Marcin; Sobczuk, Piotr; Pawlowska, Elzbieta; Blasiak, Janusz","year":2024,"journal":"Molecules (Basel, Switzerland), 29(14)","doi":"10.3390/molecules29143385","pmid":"39064963","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review synthesizes evidence proposing a signaling pathway from oxidative stress to migraine:\n\n1. Many migraine triggers (sleep deprivation, alcohol, hormonal changes, certain foods) increase reactive oxygen and nitrogen species (RONS)\n2. TRPA1 ion channels on trigeminal nerve endings are activated by oxidative stress products\n3. TRPA1 activation triggers CGRP release from nerve endings\n4. Released CGRP causes vasodilation, neurogenic inflammation, and pain — the hallmarks of migraine\n\nThe authors propose TRPA1 as the critical molecular link in this pathway and as a druggable target upstream of CGRP.","whyItMatters":"A substantial proportion of migraine patients do not respond adequately to anti-CGRP drugs. Targeting TRPA1 — the upstream trigger that causes CGRP release — could provide relief for these non-responders. Additionally, TRPA1 blockade would prevent CGRP release rather than neutralizing it after the fact, potentially offering more complete migraine prevention.","specificNumbers":"","methodology":"Narrative review synthesizing published research on oxidative stress in migraine pathogenesis, TRPA1 ion channel biology, and the CGRP signaling pathway. No original experimental data were generated.","limitations":"This is a narrative review proposing a hypothesis based on existing evidence — the TRPA1-CGRP pathway in migraine has not been definitively proven in clinical studies. TRPA1 has many functions beyond migraine, and blocking it could have off-target effects. The relationship between oxidative stress and migraine is correlational in many studies, not causal. No TRPA1-specific migraine drug has been tested in clinical trials."},{"rthcId":"RPEP-08201","title":"Efficacy of Semaglutide in Reactive Hypoglycemia Related to Dumping Syndrome after Bariatric Surgery.","authors":"Fiore, Angelo; Gaetano, Santoro; Ausilia, Lombardo; Federica, Spitali; Giulia, Sceusa; Damiano, Gullo","year":2024,"journal":"Endocrine, metabolic & immune disorders drug targets","doi":"10.2174/0118715303318399240715065513","pmid":"39041260","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08202","title":"Soluble antigen arrays provide increased efficacy and safety over free peptides for tolerogenic immunotherapy.","authors":"Firdessa-Fite, Rebuma; Johnson, Stephanie N; Bechi Genzano, Camillo; Leon, Martin A; Ku, Amy; Ocampo Gonzalez, Fernando A; Milner, Joshua D; Sestak, Joshua O; Berkland, Cory; Creusot, Remi J","year":2024,"journal":"Frontiers in immunology, 15, 1258369","doi":"10.3389/fimmu.2024.1258369","pmid":"38933266","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08203","title":"Cell-Penetrating Peptide Delivery of Nucleic Acid Cargo to Emiliania huxleyi, a Calcifying Marine Coccolithophore.","authors":"Flavin, Cory; Chatterjee, Anushree","year":2024,"journal":"ACS synthetic biology, 13(1), 77-84","doi":"10.1021/acssynbio.3c00670","pmid":"38147049","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08204","title":"Parathyroid Hormone-Related Peptide Secretion From a Pancreatic Neuroendocrine Tumor: A Rare Case Report of Severe Hypercalcemia.","authors":"Foley, Erin; Hari Dass, Prashanth; O'Sullivan, Esther","year":2024,"journal":"AACE clinical case reports, 10(4), 160-163","doi":"10.1016/j.aace.2024.04.009","pmid":"39100635","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A 56-year-old woman with a pancreatic neuroendocrine tumor (pNET) developed severe hypercalcemia caused by tumor secretion of PTHrP — a complication reported in only 1.1% of pNET cases.\n\nDespite treatment with IV fluids, bisphosphonates, calcitonin, and denosumab (a RANKL inhibitor), hypercalcemia recurred repeatedly. Adjunctive somatostatin analog therapy also failed to control calcium levels. The patient was not a candidate for curative surgery (cytoreduction). She died from refractory hypercalcemia — the metabolic complication, not the tumor itself, was the cause of death.","whyItMatters":"Pancreatic neuroendocrine tumors are often slow-growing and manageable, but when they secrete PTHrP, the resulting hypercalcemia can be rapidly fatal and resistant to standard treatments. This case underscores the need for early identification of PTHrP-secreting tumors so that surgical cytoreduction — the most effective treatment — can be attempted before the metabolic complications become uncontrollable.","specificNumbers":"","methodology":"Single-patient case report documenting clinical presentation, diagnostic workup (identifying PTHrP secretion as the cause of hypercalcemia), treatment attempts, and outcome over the disease course.","limitations":"As a single case report, no generalizable treatment conclusions can be drawn. The patient was unfit for curative surgery, so the potential benefit of cytoreduction couldn't be assessed. Alternative therapies (cinacalcet, newer anti-PTHrP approaches) were not discussed."},{"rthcId":"RPEP-08205","title":"The GLP-1 medicines semaglutide and tirzepatide do not alter disease-related pathology, behaviour or cognitive function in 5XFAD and APP/PS1 mice.","authors":"Forny Germano, Leticia; Koehler, Jacqueline A; Baggio, Laurie L; Cui, Fiona; Wong, Chi Kin; Rittig, Nikolaj; Cao, Xiemin; Matthews, Dianne; Drucker, Daniel J","year":2024,"journal":"Molecular metabolism, 89, 102019","doi":"10.1016/j.molmet.2024.102019","pmid":"39216535","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08206","title":"Biomimetic electrospun PVDF/self-assembling peptide piezoelectric scaffolds for neural stem cell transplantation in neural tissue engineering.","authors":"Forouharshad, Mahdi; Raspa, Andrea; Fortino, Giuseppe; Ciulla, Maria Gessica; Farazdaghi, Arman; Stolojan, Vlad; Stendardo, Luca; Bracco, Silvia; Gelain, Fabrizio","year":2024,"journal":"RSC advances, 14(30), 21277-21291","doi":"10.1039/d4ra02309a","pmid":"38974226","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08207","title":"The role of incretin receptor agonists in the treatment of obesity.","authors":"Forst, Thomas; De Block, Christophe; Del Prato, Stefano; Armani, Sara; Frias, Juan; Lautenbach, Anne; Ludvik, Bernhard; Marinez, Marina; Mathieu, Chantal; Müller, Timo D; Schnell, Oliver","year":2024,"journal":"Diabetes, obesity & metabolism, 26(10), 4178-4196","doi":"10.1111/dom.15796","pmid":"39072877","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08208","title":"Peptide Receptor Radionuclide Therapy or Everolimus in Metastatic Neuroendocrine Tumors: The SeqEveRIV Study, a National Study from the French Group of Endocrine Tumors and Endocan-RENATEN Network.","authors":"Fosse, Aurelien; Hadoux, Julien; Girot, Paul; Beron, Amandine; Afchain, Pauline; Cottereau, Anne-Segolene; Baudin, Eric; Dierickx, Lawrence O; Lecomte, Thierry; Perrier, Marine; Lepage, Come; Bouhier-Leporrier, Karine; Goichot, Bernard; Lachachi, Boumediene; Walter, Thomas; Durand, Alice","year":2024,"journal":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 65(9), 1416-1422","doi":"10.2967/jnumed.123.267363","pmid":"39089810","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08209","title":"Mesenchymal stem cells aligned and stretched in self-assembling peptide hydrogels.","authors":"Fouladgar, Farzaneh; Zadeh Moslabeh, Forough Ghasem; Kasani, Yashesh Varun; Rogozinski, Nick; Torres, Marc; Ecker, Melanie; Yang, Huaxiao; Yang, Yong; Habibi, Neda","year":2024,"journal":"Heliyon, 10(1), e23953","doi":"10.1016/j.heliyon.2023.e23953","pmid":"38234902","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Fmoc-diphenylalanine (Fmoc-FF) peptides self-assembled into hydrogels with nanofiber morphology and compressive moduli of 174-277 Pa, mimicking features of the natural extracellular matrix. Three solvent systems were tested: DMSO, HFP, and deionized water.\n\nHuman mesenchymal stem cells (MSCs) encapsulated in the peptide hydrogels and subjected to mechanical stretching exhibited elongated morphology with distinct microfilament fibers, compared to control cells that remained round and spherical. Peptide gels at 5 mM concentration maintained 100% MSC viability. The Fmoc-FF/HFP and Fmoc-FF/DMSO preparations produced the best results for cell alignment after stretching.","whyItMatters":"One of the biggest challenges in tissue engineering is getting cells to organize into the aligned, structured patterns found in real tissues like muscles, tendons, and blood vessels. Self-assembling peptide hydrogels offer a unique advantage: they form nanofiber scaffolds that resemble natural collagen, and when combined with mechanical stimulation, they can guide stem cells into tissue-like alignment. This brings us closer to building functional replacement tissues in the lab.","specificNumbers":"","methodology":"The researchers prepared Fmoc-FF peptide hydrogels using three different solvents (DMSO, HFP, and deionized water) and characterized their self-assembly, nanofiber morphology, and mechanical properties. Human MSCs were encapsulated in the hydrogels and placed in a custom-built mechanical stretching device with a PDMS chamber. Cell viability, morphology, and alignment were assessed using various staining techniques including F-actin visualization.","limitations":"This was an in vitro study with no animal or human testing. The mechanical properties of the hydrogels (174-277 Pa) are much softer than most native tissues, which may limit their immediate application for load-bearing tissue engineering. Long-term cell behavior, differentiation potential within the gels, and in vivo performance were not assessed. The solvents used for gel preparation (DMSO, HFP) require careful removal to avoid toxicity in clinical applications."},{"rthcId":"RPEP-08210","title":"JNJ-77242113, a highly potent, selective peptide targeting the IL-23 receptor, provides robust IL-23 pathway inhibition upon oral dosing in rats and humans.","authors":"Fourie, Anne M; Cheng, Xiaoli; Chang, Leon; Greving, Carrie; Li, Xinyi; Knight, Beverly; Polidori, David; Patrick, Aaron; Bains, Trpta; Steele, Ruth; Allen, Samantha J; Patch, Raymond J; Sun, Chengzao; Somani, Sandeep; Bhandari, Ashok; Liu, David; Huie, Keith; Li, Shu; Rodriguez, Michael A; Xue, Xiaohua; Kannan, Arun; Kosoglou, Teddy; Sherlock, Jonathan P; Towne, Jennifer; Holland, M Claire; Modi, Nishit B","year":2024,"journal":"Scientific reports, 14(1), 17515","doi":"10.1038/s41598-024-67371-5","pmid":"39080319","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08211","title":"Tirzepatide: A Review in Type 2 Diabetes.","authors":"France, Nicole L; Syed, Yahiya Y","year":2024,"journal":"Drugs, 84(2), 227-238","doi":"10.1007/s40265-023-01992-4","pmid":"38388874","tags":["glp-1-agonists","diabetes"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Tirzepatide (Mounjaro), the first dual GIP/GLP-1 receptor agonist, demonstrated superiority over multiple established diabetes treatments in the phase III SURPASS clinical trial program. Given once weekly by subcutaneous injection, tirzepatide outperformed dulaglutide 0.75 mg, semaglutide 1 mg, and both basal and prandial insulin for both blood sugar control and weight loss in adults with inadequately controlled type 2 diabetes.\n\nThe drug showed a favorable safety profile consistent with GLP-1 receptor agonists, with a low risk of clinically significant hypoglycemia and no increased risk of major adverse cardiovascular events. The most common side effects were gastrointestinal — nausea, diarrhea, decreased appetite, and vomiting — and were mostly mild to moderate.","whyItMatters":"Tirzepatide represents a paradigm shift in diabetes treatment by being the first approved drug to simultaneously activate both GIP and GLP-1 receptors. Its superiority over semaglutide — already considered one of the most effective GLP-1 drugs — in both glycemic control and weight loss establishes a new benchmark for incretin-based therapy. The dual mechanism suggests that combining incretin pathways may be more effective than targeting GLP-1 alone, opening a new chapter in metabolic disease treatment.","specificNumbers":"Once-weekly subcutaneous injection · superior to semaglutide 1 mg · superior to dulaglutide 0.75 mg · superior to basal and prandial insulin · low hypoglycemia risk · no increased cardiovascular risk · approved in USA, EU, Japan","methodology":"This is a published drug review article summarizing evidence from the phase III SURPASS clinical trial program. The SURPASS trials evaluated tirzepatide as monotherapy and as add-on therapy to oral glucose-lowering medications and insulin across multiple randomized controlled trials in adults with type 2 diabetes.","limitations":"As a review article, this summarizes existing trial data rather than presenting new findings. The SURPASS trials compared tirzepatide to specific doses of competitors (semaglutide 1 mg, dulaglutide 0.75 mg), and comparisons at different doses might yield different results. Long-term safety data beyond the trial periods is still accumulating. The review focuses on type 2 diabetes; weight management approval data (SURMOUNT trials) is addressed separately."},{"rthcId":"RPEP-08212","title":"Clinical Effects of Glucagon-Like Peptide-1 Agonist Use for Weight Loss in Women With Polycystic Ovary Syndrome: A Scoping Review.","authors":"Frangie Machado, Melissa; Shunk, Taylor; Hansen, Grace; Harvey, Charles; Fulford, Baylee; Hauf, Shane; Schuh, Olivia; Kaldas, Matthew; Arcaroli, Elena; Ortiz, Justin; De Gaetano, Joseph","year":2024,"journal":"Cureus, 16(8), e66691","doi":"10.7759/cureus.66691","pmid":"39262529","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"All eight included studies uniformly reported reductions in weight and BMI among PCOS patients prescribed GLP-1 RAs (liraglutide or exenatide). Additional benefits included improvements in anthropometric parameters (waist circumference, total fat percentage), glucose homeostasis, cardiovascular inflammatory markers (MR-proANP and MR-proADM), rates of natural pregnancy, and menstrual regulation.\n\nHowever, findings regarding lipid profile effects were inconsistent across studies. Short-term adverse effects were noted but long-term effects remain undetermined. The studies showed wide geographic diversity, suggesting benefits across racial and ethnic backgrounds.","whyItMatters":"PCOS affects 6-12% of reproductive-age women and is the leading cause of infertility related to anovulation. Weight management is central to PCOS treatment, but effective pharmacological options have been limited. GLP-1 receptor agonists address multiple PCOS features simultaneously — weight, insulin resistance, metabolic dysfunction, and potentially fertility — making them a particularly attractive therapeutic option for this population.","specificNumbers":"","methodology":"Scoping review following Joanna Briggs Institute methodology and PRISMA guidelines. Searched Ovid Medline, Web of Science, CINAHL, Cochrane CENTRAL, SCOPUS, and ClinicalTrials.gov from 2012 to 2023. From 811 identified articles (after duplicate removal), eight met eligibility criteria. All were peer-reviewed, published in English, and examined GLP-1 RAs in women with PCOS.","limitations":"Only eight studies met inclusion criteria, limiting the evidence base. Most studies used liraglutide or exenatide rather than newer agents (semaglutide, tirzepatide). Long-term effects remain undetermined. The review is a scoping review, not a systematic review with meta-analysis, so effect sizes cannot be pooled. Lipid profile effects were inconsistent. Study designs and outcome measures varied across included studies."},{"rthcId":"RPEP-08213","title":"Real-world HbA1c changes and prescription characteristics among type 2 diabetes mellitus patients initiating treatment with once weekly semaglutide for diabetes.","authors":"Frazer, Monica; Swift, Caroline; Sargent, Andrew; Leszko, Michael; Buysman, Erin; Gronroos, Noelle N; Alvarez, Sara; Dunn, Tyler J; Noone, Josh; Gamble, Cory L","year":2024,"journal":"Journal of diabetes and metabolic disorders, 23(1), 727-737","doi":"10.1007/s40200-023-01341-y","pmid":"38932879","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08214","title":"Analysis of clinical studies on clozapine from 2012-2022.","authors":"Freibüchler, Anton; Seifert, Roland","year":2024,"journal":"Naunyn-Schmiedeberg's archives of pharmacology, 397(12), 9745-9765","doi":"10.1007/s00210-024-03209-1","pmid":"38918233","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"From 64 clinical studies on clozapine (2012-2022), key findings included:\n\n- No investigated drug was superior to clozapine for schizophrenia treatment\n- Clozapine was superior to olanzapine and risperidone for aggression and depression reduction\n- Metabolic parameters changed comparably between clozapine and olanzapine after 8 years\n- Eight drugs identified as potentially effective for clozapine-induced weight gain, including the GLP-1 receptor agonists liraglutide and exenatide, alongside metformin and orlistat\n- Scopolamine, atropine drops, and metoclopramide were effective for clozapine-induced hypersalivation\n- Ziprasidone, haloperidol, and aripiprazole showed positive augmentation effects when added to clozapine","whyItMatters":"Antipsychotic-induced weight gain is a major clinical problem affecting millions of psychiatric patients worldwide, contributing to diabetes, cardiovascular disease, and treatment non-adherence. The identification of GLP-1 receptor agonists as effective for clozapine-induced weight gain opens a significant new application for these peptide drugs. As GLP-1 drugs become more accessible and affordable, their role in managing metabolic side effects of psychiatric medications could expand substantially.","specificNumbers":"","methodology":"The authors conducted a systematic literature review using PubMed to identify clinical studies on clozapine published between 2012 and 2022. Sixty-four studies met inclusion criteria and were categorized by topic: pharmacokinetics, efficacy comparisons, side effect management, and augmentation strategies. Results were synthesized narratively across categories.","limitations":"This is a narrative review, not a systematic review with formal meta-analysis or quality assessment. The weight gain management section identifies drugs as 'potentially effective' without quantifying effect sizes or providing comparative efficacy data. The GLP-1 drug evidence is summarized alongside six other drugs without distinguishing which are most effective. The 2012-2022 search window may miss more recent data on semaglutide for antipsychotic weight gain, which has become a particularly active research area."},{"rthcId":"RPEP-08215","title":"Tirzepatide Improved Markers of Islet Cell Function and Insulin Sensitivity in People With T2D (SURPASS-2).","authors":"Frias, Juan P; De Block, Christophe; Brown, Katelyn; Wang, Hui; Thomas, Melissa K; Zeytinoglu, Meltem; Maldonado, Juan M","year":2024,"journal":"The Journal of clinical endocrinology and metabolism, 109(7), 1745-1753","doi":"10.1210/clinem/dgae038","pmid":"38252888","tags":[],"studyType":"rct-post-hoc","evidenceStrength":"high","keyFinding":"In this post hoc analysis of the SURPASS-2 trial, tirzepatide at all three doses (5, 10, and 15 mg) outperformed semaglutide 1 mg in improving both pancreatic beta-cell function and insulin sensitivity in people with type 2 diabetes over 40 weeks.\n\nTirzepatide improved HOMA2-B (beta-cell function) by 96.9–120.4% compared to 84.0% with semaglutide (p<0.05). Insulin resistance (HOMA2-IR) decreased by 15.5–24.0% with tirzepatide versus only 5.1% with semaglutide (p<0.05). Tirzepatide 10 and 15 mg also significantly reduced fasting C-peptide (5.2–6.0%) and fasting glucagon (53.0–55.3%) compared to semaglutide. These advantages in HbA1c and weight loss held across all baseline quartiles of beta-cell function and insulin resistance.","whyItMatters":"This head-to-head comparison with semaglutide — the leading GLP-1 drug — demonstrates that tirzepatide's dual GIP/GLP-1 mechanism produces superior improvements in the fundamental metabolic defects of type 2 diabetes: failing beta cells and insulin resistance. This goes beyond symptom management to address root causes.","specificNumbers":"n=1,879 · 40 weeks · HOMA2-B improvement: 96.9–120.4% (tirzepatide) vs 84.0% (semaglutide) · HOMA2-IR reduction: 15.5–24.0% vs 5.1% · p<0.05","methodology":"Post hoc analysis of the SURPASS-2 phase 3 randomized controlled trial. 1,879 participants with type 2 diabetes across 128 sites in 8 countries were assigned to weekly subcutaneous tirzepatide (5, 10, or 15 mg) or semaglutide 1 mg for 40 weeks. Biomarkers of beta-cell function (HOMA2-B) and insulin resistance (HOMA2-IR), along with fasting glucagon, C-peptide, and insulin were measured.","limitations":"This is a post hoc analysis, not a prespecified endpoint, which means the findings are hypothesis-generating rather than confirmatory. The semaglutide comparator was limited to 1 mg (the maximum approved dose at trial initiation), not the higher 2 mg dose now available."},{"rthcId":"RPEP-08216","title":"Peptide Receptor Radionuclide Therapy Is Effective for Clinical Control of Symptomatic Metastatic Insulinoma: A Long-Term Retrospective Analysis.","authors":"Friebe, Liene; Freitag, Martin T; Braun, Martin; Nicolas, Guillaume; Bauman, Andreas; Bushnell, David; Christ, Emanuel; Wild, Damian","year":2024,"journal":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 65(2), 228-235","doi":"10.2967/jnumed.123.265894","pmid":"38164592","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08217","title":"Advances in understanding migraine pathophysiology: a bench to bedside review of research insights and therapeutics.","authors":"Frimpong-Manson, Kofi; Ortiz, Yuma T; McMahon, Lance R; Wilkerson, Jenny L","year":2024,"journal":"Frontiers in molecular neuroscience, 17, 1355281","doi":"10.3389/fnmol.2024.1355281","pmid":"38481473","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08218","title":"Monoclonal Antibodies Targeting CGRP to Treat Vestibular Migraine: A Rapid Systematic Review and Meta-Analysis.","authors":"Frosolini, Andrea; Lovato, Andrea","year":2024,"journal":"Indian journal of otolaryngology and head and neck surgery : official publication of the Association of Otolaryngologists of India, 76(4), 3737-3744","doi":"10.1007/s12070-024-04578-y","pmid":"39130214","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08219","title":"The influence of nutritional status, lipid profile, leptin concentration and polymorphism of genes encoding leptin and neuropeptide Y on the effectiveness of immunotherapy in advanced NSCLC patients.","authors":"Frąk, Małgorzata; Grenda, Anna; Krawczyk, Paweł; Kuźnar-Kamińska, Barbara; Pazdrowski, Paweł; Kędra, Karolina; Chmielewska, Izabela; Milanowski, Janusz","year":2024,"journal":"BMC cancer, 24(1), 937","doi":"10.1186/s12885-024-12716-6","pmid":"39090596","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08220","title":"SGLT-2 inhibitors, GLP-1 receptor agonists, and DPP-4 inhibitors and risk of hyperkalemia among people with type 2 diabetes in clinical practice: population based cohort study.","authors":"Fu, Edouard L; Wexler, Deborah J; Cromer, Sara J; Bykov, Katsiaryna; Paik, Julie M; Patorno, Elisabetta","year":2024,"journal":"BMJ (Clinical research ed.), 385, e078483","doi":"10.1136/bmj-2023-078483","pmid":"38925801","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08221","title":"Biomimetic Supramolecular Assembly with IGF-1C Delivery Ameliorates Inflammatory Bowel Disease (IBD) by Restoring Intestinal Barrier Integrity.","authors":"Fu, Enze; Qian, Meng; He, Ningning; Yin, Yilun; Liu, Yue; Han, Zhibo; Han, ZhongChao; Zhao, Qiang; Cao, Xiaocang; Li, Zongjin","year":2024,"journal":"Advanced science (Weinheim, Baden-Wurttemberg, Germany), 11(36), e2403075","doi":"10.1002/advs.202403075","pmid":"39041890","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08222","title":"Targeting EFHD2 inhibits interferon-γ signaling and ameliorates non-alcoholic steatohepatitis.","authors":"Fu, Jiang-Tao; Liu, Jian; Wu, Wen-Bin; Chen, Yi-Ting; Lu, Guo-Dong; Cao, Qi; Meng, Hong-Bo; Tong, Jie; Zhu, Jia-Hui; Wang, Xu-Jie; Liu, Yi; Zhuang, Chunlin; Sheng, Chunquan; Shen, Fu-Ming; Liu, Xingguang; Wang, Hua; Yu, Yongsheng; Zhang, Yuefan; Liang, Hai-Yan; Zhang, Jia-Bao; Li, Dong-Jie; Li, Xiang; Wang, Zhi-Bin; Wang, Pei","year":2024,"journal":"Journal of hepatology, 81(3), 389-403","doi":"10.1016/j.jhep.2024.04.009","pmid":"38670321","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08223","title":"Exendin-4 intervention attenuates atherosclerosis severity by modulating myeloid-derived suppressor cells and inflammatory cytokines in ApoE-/- mice.","authors":"Fu, Miaoxin; Li, Qingmei; Qian, Hang; Min, Xinwen; Yang, Handong; Liu, Zhixin; Wu, Wenwen; Zhong, Jixin; Xu, Hao; Mei, Aihua; Chen, Jun","year":2024,"journal":"International immunopharmacology, 140, 112844","doi":"10.1016/j.intimp.2024.112844","pmid":"39094363","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08224","title":"Acupuncture improves the symptoms, serum ghrelin, and autonomic nervous system of patients with postprandial distress syndrome: a randomized controlled trial.","authors":"Fu, Zi-Tong; Liu, Cun-Zhi; Kim, Mi-Rim; Liu, Yi-Duo; Wang, Yu; Fu, Yi-Ming; Yang, Jing-Wen; Yang, Na-Na","year":2024,"journal":"Chinese medicine, 19(1), 162","doi":"10.1186/s13020-024-01028-3","pmid":"39568071","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08225","title":"Achieving normoglycaemia with tirzepatide: Post hoc exploratory analysis of the SURPASS J-mono and J-combo studies.","authors":"Fujihara, Kazuya; Matsubayashi, Yasuhiro; Kitazawa, Masaru; Sato, Takaaki; Takeuchi, Masakazu; Oura, Tomonori; Sone, Hirohito","year":2024,"journal":"Diabetes, obesity & metabolism, 26(11), 5304-5311","doi":"10.1111/dom.15887","pmid":"39192522","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08226","title":"Effect of heart rate on B-type natriuretic peptide in sinus rhythm.","authors":"Fukushima, Keisuke; Ogawa, Kazuo; Kawai, Makoto; Yoshimura, Michihiro","year":2024,"journal":"Scientific reports, 14(1), 31711","doi":"10.1038/s41598-024-81922-w","pmid":"39738157","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08227","title":"Cagrilintide is not associated with clinically relevant QTc prolongation: A thorough QT study in healthy participants.","authors":"Gabe, Maria B N; Fuhr, Rainard; Sinn, Angela; Eliasen, Astrid; Berthelsen, Kasper K; Kuhlman, Anja B; Bækdal, Tine A; Nejad, Ayna B","year":2024,"journal":"Diabetes, obesity & metabolism, 26(12), 5805-5811","doi":"10.1111/dom.15951","pmid":"39279639","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08228","title":"Effect of oral semaglutide on energy intake, appetite, control of eating and gastric emptying in adults living with obesity: A randomized controlled trial.","authors":"Gabe, Maria Buur Nordskov; Breitschaft, Astrid; Knop, Filip Krag; Hansen, Morten Rix; Kirkeby, Katrine; Rathor, Naveen; Adrian, Charlotte Lindorff","year":2024,"journal":"Diabetes, obesity & metabolism, 26(10), 4480-4489","doi":"10.1111/dom.15802","pmid":"39082206","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08229","title":"Therapeutic Effects of Semaglutide on Nonalcoholic Fatty Liver Disease with Type 2 Diabetes Mellitus and Obesity: An Open-Label Controlled Trial.","authors":"Gad, Ahmed I; Ibrahim, Nevin F; Almadani, Noura; Mahfouz, Rasha; Nofal, Hanaa A; El-Rafey, Dina S; Ali, Hossam Tharwat; El-Hawary, Amr T; Sadek, Ayman M E M","year":2024,"journal":"Diseases (Basel, Switzerland), 12(8)","doi":"10.3390/diseases12080186","pmid":"39195185","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08230","title":"Case report: Nerve fiber regeneration in children with melanocortin 4 receptor gene mutation related obesity treated with semaglutide.","authors":"Gad, Hoda; Mohammed, Idris; Dauleh, Hajar; Pasha, Maheen; Al-Barazenji, Tara; Hussain, Khalid; Malik, Rayaz A","year":2024,"journal":"Frontiers in endocrinology, 15, 1385463","doi":"10.3389/fendo.2024.1385463","pmid":"38974580","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08231","title":"Rapid Improvement in Weight, Body Composition, and Glucose Variability With Semaglutide in Type 1 Diabetes.","authors":"Gad, Hoda; Malik, Rayaz A","year":2024,"journal":"Cureus, 16(6), e61577","doi":"10.7759/cureus.61577","pmid":"38962634","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In a 34-year-old woman with 23 years of type 1 diabetes, adding semaglutide (1 mg weekly) to insulin therapy produced dramatic improvements in just 2 months: 12 kg weight loss (63→51 kg), 15% reduction in body fat percentage, 7% decrease in visceral fat, reduced HbA1c (from 8.3%), lower insulin doses, and decreased glycemic variability.","whyItMatters":"GLP-1 receptor agonists are not approved for type 1 diabetes, yet many T1D patients struggle with weight gain and glucose instability on insulin alone. This case shows that semaglutide may be a valuable adjunct in T1D — addressing multiple problems simultaneously (weight, body composition, glucose control, insulin requirements) — and could prompt formal clinical trials in this population.","specificNumbers":"Weight: 63→51 kg (-12 kg) · body fat: -15% · visceral fat: -7% · HbA1c from 8.3% · BMI from 26.9 · semaglutide 1 mg weekly · 2-month results","methodology":"Single case report. A 34-year-old woman with longstanding T1DM (23 years) was started on subcutaneous semaglutide 1 mg weekly as an adjunct to existing insulin therapy. Weight, body composition (body fat %, visceral fat), HbA1c, glycemic variability, and insulin dose were assessed at baseline and after 2 months.","limitations":"Single case report (n=1) — cannot be generalized. Two months is very short follow-up. The 12 kg weight loss in 2 months is unusually rapid and may not be sustainable. Risk of diabetic ketoacidosis (DKA) from insulin reduction in T1D was not discussed. Published in Cureus (lower-impact journal). No control or comparison period."},{"rthcId":"RPEP-08232","title":"Investigational and emerging gastric inhibitory polypeptide (GIP) receptor-based therapies for the treatment of obesity.","authors":"Gaffey, Robert H; Takyi, Afua K; Shukla, Alpana","year":2024,"journal":"Expert opinion on investigational drugs, 33(8), 757-773","doi":"10.1080/13543784.2024.2377319","pmid":"38984950","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08233","title":"Decoding the dynamics of BCL9 triazole stapled peptide.","authors":"Gaikwad, Vikram; Choudhury, Asha Rani; Chakrabarti, Rajarshi","year":2024,"journal":"Biophysical chemistry, 307, 107197","doi":"10.1016/j.bpc.2024.107197","pmid":"38335808","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08234","title":"Update on Obesity and Cardiovascular Risk: From Pathophysiology to Clinical Management.","authors":"Gallo, Giovanna; Desideri, Giovambattista; Savoia, Carmine","year":2024,"journal":"Nutrients, 16(16)","doi":"10.3390/nu16162781","pmid":"39203917","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08235","title":"Epithelial Antimicrobial Peptide/Protein and Cytokine Expression Profiles Obtained from Nasopharyngeal Swabs of SARS-CoV-2-Infected and Non-Infected Subjects.","authors":"Gambichler, Thilo; Goesmann, Silke; Skrygan, Marina; Susok, Laura; Schütte, Christian; Hamdani, Nahza; Schmidt, Wolfgang","year":2024,"journal":"Viruses, 16(9)","doi":"10.3390/v16091471","pmid":"39339947","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08236","title":"The relative risk of clinically relevant cholelithiasis among glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes mellitus, real-world study.","authors":"Gameil, Mohammed Ali; Yousef, Elshahat Ali Ahmed Mohamed; Marzouk, Rehab Elsayed; Emara, Mohamed H; Abdelkader, Abeer H; Salama, Rasha Ibrahim","year":2024,"journal":"Diabetology & metabolic syndrome, 16(1), 293","doi":"10.1186/s13098-024-01526-2","pmid":"39633496","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08237","title":"Designing Analogs of SAAP-148 with Enhanced Antimicrobial and Anti-LPS Activities.","authors":"Gan, Lingmin; Chi, Yulang; Peng, Yunhui; Li, Subo; Gao, Hongwei; Zhang, Xue; Ji, Shouping; Feng, Zili; Zhang, Shikun","year":2024,"journal":"International journal of molecular sciences, 25(21)","doi":"10.3390/ijms252111776","pmid":"39519326","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08238","title":"Implications of therapy interruption on monthly migraine days and modified migraine disability assessment in patients treated with erenumab for chronic and episodic migraine: SQUARE study interim results.","authors":"Gantenbein, Andreas R; Bonvin, Christophe; Kamm, Christian P; Schankin, Christoph J; Zecca, Chiara; Zieglgänsberger, Dominik; Merki-Feld, Gabriele Susanne; Pohl, Heiko; Rudolph, Nicole; Ryvlin, Philippe; Agosti, Reto; Schäfer, Elisabeth; Meyer, Ina; Kulartz-Schank, Monika; Arzt, Michael E","year":2024,"journal":"Journal of neurology, 271(8), 5402-5410","doi":"10.1007/s00415-024-12470-6","pmid":"38871822","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08239","title":"The evolutionary novelty of insect defensins: from bacterial killing to toxin neutralization.","authors":"Gao, Bin; Zhu, Shunyi","year":2024,"journal":"Cellular and molecular life sciences : CMLS, 81(1), 230","doi":"10.1007/s00018-024-05273-5","pmid":"38780625","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08240","title":"18F-labeled somatostatin analogs for somatostatin receptors (SSTRs) targeted PET imaging of neuroendocrine tumors (NETs).","authors":"Gao, Fei; Zhang, Yunhan; Chen, MengYi; Song, ZhiHao; Dong, RuiLin; Qiu, ShanShan; Shen, Chen; Huang, XiaoYan; Geng, Hao; Cheng, Weihua; Hu, Ji","year":2024,"journal":"European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 193, 106671","doi":"10.1016/j.ejps.2023.106671","pmid":"38104907","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A new fluorine-18-labeled somatostatin analog ([Al18F]NODA-MPAA-HTA) was synthesized with 60–80% radiochemical yield and >95% purity. It binds all five somatostatin receptor subtypes and showed a binding affinity of 8.77 nM for SSTR2. In mice bearing SSTR2-positive tumors, the tracer achieved tumor-to-muscle uptake ratios greater than 5-fold, producing high-contrast PET images with no defluorination detected in vivo.","whyItMatters":"Current PET imaging of neuroendocrine tumors primarily uses gallium-68-labeled somatostatin analogs, but fluorine-18 has advantages — its longer half-life (110 minutes vs. 68 minutes) and easier production could make these scans more widely available. This new tracer targets all five somatostatin receptor subtypes rather than just SSTR2, potentially improving detection of tumors that express different receptor profiles.","specificNumbers":"","methodology":"The researchers designed a peptide-based radiotracer by conjugating fluorine-18 to a modified KE108 somatostatin analog using aluminum-fluoride chelation chemistry. They tested its stability in saline and bovine serum, measured cellular uptake and receptor binding affinity in SSTR2-expressing cells, and performed micro-PET imaging and biodistribution studies in tumor-bearing mice.","limitations":"This is a preclinical study conducted only in cell lines and mice — no human imaging data were collected. The tumor model used cells engineered to overexpress SSTR2, which may not reflect the heterogeneous receptor expression found in actual patient tumors. Long-term toxicity and pharmacokinetics in larger animal models were not assessed."},{"rthcId":"RPEP-08241","title":"Biomimetic Peptide Nanonets: Exploiting Bacterial Entrapment and Macrophage Rerousing for Combatting Infections.","authors":"Gao, Nan; Bai, Pengfei; Fang, Chunyang; Wu, Wanpeng; Bi, Chongpeng; Wang, Jiajun; Shan, Anshan","year":2024,"journal":"ACS nano, 18(37), 25446-25464","doi":"10.1021/acsnano.4c03669","pmid":"39240217","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08242","title":"A pharmacokinetic study comparing the biosimilar HEC14028 and Dulaglutide (Trulicity®) in healthy Chinese subjects.","authors":"Gao, Xianglei; Di, Yujing; Lv, Yuan; Luan, Yingcai; Xiong, Yang; Xu, Yuli; Li, Yusheng; Guo, Linfeng; Li, Xiaoping; Deng, Li; Zhuang, Yulei; Hou, Jie","year":2024,"journal":"Clinical and translational science, 17(4), e13775","doi":"10.1111/cts.13775","pmid":"38651744","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"HEC14028 and dulaglutide were pharmacokinetically equivalent: 90% CI of Cmax ratio was 102.9%-122.0% and AUC0-∞ ratio was 97.1%-116.9%, both within the accepted 80-125% bioequivalence range. No grade 3+ adverse events, serious adverse events, or deaths occurred. No incremental immunogenicity with the biosimilar.","whyItMatters":"Biosimilar GLP-1 drugs could dramatically reduce costs and improve global access to these transformative diabetes treatments, which remain prohibitively expensive for many patients.","specificNumbers":"n=68; 1:1 randomization; 0.75 mg single dose; Cmax 90% CI: 102.9-122.0%; AUC0-∞ 90% CI: 97.1-116.9%; no grade 3+ TEAEs","methodology":"Single-center, randomized, open-label, single-dose, parallel-controlled Phase I trial. 68 healthy Chinese male subjects randomized 1:1 to HEC14028 or dulaglutide (0.75 mg subcutaneous). 14-day screening, 17-day observation, 7-day safety follow-up. Primary endpoints: Cmax and AUC0-∞ with 90% CI within 80-125% bioequivalence range.","limitations":"Only healthy male Chinese subjects — results may not fully generalize to other populations, females, or diabetic patients. Single-dose study doesn't capture steady-state pharmacokinetics. Only the 0.75 mg dose tested (not the standard 1.5 mg therapeutic dose). Open-label design. Small sample size (n=68). Safety profile with longer-term use unknown."},{"rthcId":"RPEP-08243","title":"Development of 1 Month Sustained-Release Microspheres Containing Liraglutide for Type 2 Diabetes Treatment.","authors":"Gao, Zejing; Wei, Yi; Ge, Jia; Liu, Jingxuan; Qin, Ying; Gong, Fangling; Ma, Guanghui","year":2024,"journal":"ACS applied materials & interfaces, 16(20), 25869-25878","doi":"10.1021/acsami.4c04010","pmid":"38728411","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08244","title":"Phenotypic drug discovery: a case for thymosin alpha-1.","authors":"Garaci, Enrico; Paci, Maurizio; Matteucci, Claudia; Costantini, Claudio; Puccetti, Paolo; Romani, Luigina","year":2024,"journal":"Frontiers in medicine, 11, 1388959","doi":"10.3389/fmed.2024.1388959","pmid":"38903817","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08245","title":"Relationship of proteins and subclinical cardiovascular traits in the population-based LIFE-Adult study.","authors":"Garcia, Tarcyane; Petrera, Agnese; Hauck, Stefanie M; Baber, Ronny; Wirkner, Kerstin; Kirsten, Holger; Pott, Janne; Tönjes, Anke; Henger, Sylvia; Loeffler, Markus; Peters, Annette; Scholz, Markus","year":2024,"journal":"Atherosclerosis, 398, 118613","doi":"10.1016/j.atherosclerosis.2024.118613","pmid":"39340936","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Of 92 cardiovascular-related proteins measured, 43 were significantly associated with at least one of 13 subclinical cardiovascular traits. NT-proBNP (a peptide biomarker of heart stress), brachial-ankle pulse-wave velocity (arterial stiffness), and carotid plaque burden had the most protein associations.\n\nOnly three proteins — growth/differentiation factor 15, LDL receptor, and interleukin-1 receptor type 2 — were associated with all three of these key traits. Several novel associations were discovered: von Willebrand factor and galectin 4 with carotid plaque, carboxypeptidase A1 and B1 with carotid intima-media thickness, cathepsin D with arterial stiffness, and cathepsin Z, LDL receptor, neurogenic locus homolog protein 3, and TREM-like transcript 2 with NT-proBNP. Sex-specific effects were also observed for some proteins.","whyItMatters":"Detecting cardiovascular disease before symptoms appear is critical for prevention. This study maps out which proteins in the blood are linked to early, hidden disease processes — long before a heart attack or stroke occurs. The newly discovered protein associations could lead to better blood tests for early risk prediction and identify new biological targets for preventive therapies.","specificNumbers":"","methodology":"Researchers measured 92 cardiovascular-disease-related proteins using the Olink Cardiovascular III panel in 2,024 elderly participants from the population-based LIFE-Adult study in Germany. They analyzed associations between these proteins and 13 subclinical cardiovascular traits including carotid intima-media thickness, plaque burden, pulse-wave velocities, ankle-brachial index, and NT-proBNP levels, while controlling for 27 covariables including blood counts, risk factors, and lifestyle parameters.","limitations":"This is a cross-sectional, observational study, so it cannot establish whether the identified proteins cause cardiovascular changes or are simply markers of them. The study population was elderly and from a single geographic region (Germany), which may limit generalizability. The protein panel was limited to 92 pre-selected cardiovascular proteins, potentially missing important associations with proteins not included in the panel."},{"rthcId":"RPEP-08246","title":"Efficacy of Semaglutide in Overweight and Obese Patients with Type 1 Diabetes.","authors":"Garg, Satish K; Kaur, Gurleen; Haider, Zehra; Rodriquez, Erika; Beatson, Christie; Snell-Bergeon, Janet","year":2024,"journal":"Diabetes technology & therapeutics, 26(3), 184-189","doi":"10.1089/dia.2023.0490","pmid":"38444317","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08247","title":"Host defense peptides at the crossroad of endothelial cell physiology: Insight into mechanistic and pharmacological implications.","authors":"Garg, Vivek Kumar; Joshi, Hemant; Sharma, Amarish Kumar; Yadav, Kiran; Yadav, Vikas","year":2024,"journal":"Peptides, 182, 171320","doi":"10.1016/j.peptides.2024.171320","pmid":"39547414","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08248","title":"Future Medications for Obesity and Clinical Implications.","authors":"Garvey, W Timothy","year":2024,"journal":"Diabetes spectrum : a publication of the American Diabetes Association, 37(4), 325-334","doi":"10.2337/dsi24-0004","pmid":"39649698","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08249","title":"Xanthan gum and pectin as beverage stabilizers reduce the digestive enzyme hydrolysis of antioxidant and antihypertensive peptides obtained from a brewery byproduct.","authors":"Garzón, A G; Pontoni, S M; Mamone, G; Drago, S R; Cian, R E","year":2024,"journal":"Food research international (Ottawa, Ont.), 177, 113836","doi":"10.1016/j.foodres.2023.113836","pmid":"38225113","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08250","title":"One-Year Weight Reduction With Semaglutide or Liraglutide in Clinical Practice.","authors":"Gasoyan, Hamlet; Pfoh, Elizabeth R; Schulte, Rebecca; Le, Phuc; Butsch, W Scott; Rothberg, Michael B","year":2024,"journal":"JAMA network open, 7(9), e2433326","doi":"10.1001/jamanetworkopen.2024.33326","pmid":"39269703","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08251","title":"Antinociceptive Behavior, Glutamine/Glutamate, and Neopterin in Early-Stage Streptozotocin-Induced Diabetic Neuropathy in Liraglutide-Treated Mice under a Standard or Enriched Environment.","authors":"Gateva, Pavlina; Hristov, Milen; Ivanova, Natasha; Vasileva, Debora; Ivanova, Alexandrina; Sabit, Zafer; Bogdanov, Todor; Apostolova, Sonia; Tzoneva, Rumiana","year":2024,"journal":"International journal of molecular sciences, 25(19)","doi":"10.3390/ijms251910786","pmid":"39409118","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Liraglutide (0.4 mg/kg daily for 10 days) did not reduce blood sugar in streptozotocin-diabetic mice but significantly alleviated pain behavior. In the formalin test, liraglutide-treated mice in an enriched environment showed dramatically lower second-phase pain responses compared to standard housing [2.00 vs 29.00 seconds, p=0.016]. Liraglutide reduced neopterin levels (an inflammation marker) compared to untreated diabetic controls. The glutamine/glutamate ratio was significantly higher with liraglutide treatment or enriched environment compared to diabetic controls (p=0.003 and p=0.002, respectively).","whyItMatters":"Diabetic neuropathy affects up to 50% of diabetes patients and current treatments only manage symptoms. The finding that liraglutide reduces neuropathic pain independently of blood sugar control suggests GLP-1 drugs may have direct neuroprotective effects. The environmental enrichment finding adds an intriguing non-pharmacological dimension to neuropathy management.","specificNumbers":"","methodology":"Type 1 diabetes was induced in mice with streptozotocin (150 mg/kg i.p.). Mice received liraglutide (0.4 mg/kg daily i.p. for 10 days starting day 8 post-induction) and were housed in either standard laboratory or enriched environments. Pain was assessed using formalin and von Frey tests. Blood glucose, neopterin, and glutamine/glutamate ratios were measured.","limitations":"This is a mouse study using chemically-induced type 1 diabetes, which may not perfectly model human diabetic neuropathy. Liraglutide did not lower blood sugar, limiting its relevance as a diabetes treatment in this model. The 10-day treatment period is short. The von Frey results were mixed (decreased threshold), suggesting complex effects on different pain modalities. Sample sizes were not reported in the abstract."},{"rthcId":"RPEP-08252","title":"Impact of exenatide on weight loss and eating behavior in adults with craniopharyngioma-related obesity: the CRANIOEXE randomized placebo-controlled trial.","authors":"Gatta-Cherifi, Blandine; Mohammedi, Kamel; Cariou, Tanguy; Poitou, Christine; Touraine, Philippe; Raverot, Gerald; Brue, Thierry; Chanson, Philippe; Illouz, Frédéric; Grunenwald, Solange; Chabre, Olivier; Sonnet, Emmanuel; Cuny, Thomas; Bertherat, Jerôme; Czernichow, Sébastien; Frison, Eric; Tabarin, Antoine","year":2024,"journal":"European journal of endocrinology, 190(4), 257-265","doi":"10.1093/ejendo/lvae024","pmid":"38450721","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08253","title":"Exploring the role of GHRH antagonist MIA-602 in overcoming Doxorubicin-resistance in acute myeloid leukemia.","authors":"Gaumond, Simonetta I; Abdin, Rama; Costoya, Joel; Schally, Andrew V; Jimenez, Joaquin J","year":2024,"journal":"Oncotarget, 15, 248-254","doi":"10.18632/oncotarget.28579","pmid":"38588464","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08254","title":"Microplastic and the Enteric Nervous System: Effect of PET Microparticles on Selected Neurotransmitters and Cytokines in the Porcine Ileum.","authors":"Gałęcka, Ismena; Całka, Jarosław","year":2024,"journal":"International journal of molecular sciences, 25(21)","doi":"10.3390/ijms252111645","pmid":"39519197","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08255","title":"Oral Exposure to Microplastics Affects the Neurochemical Plasticity of Reactive Neurons in the Porcine Jejunum.","authors":"Gałęcka, Ismena; Całka, Jarosław","year":2024,"journal":"Nutrients, 16(14)","doi":"10.3390/nu16142268","pmid":"39064711","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"After 28 days of oral PET microplastic exposure in pigs:\n- Galanin-positive neurons increased across the gut nervous system\n- VIP-positive, CART-positive, and vesicular acetylcholine transporter-positive neurons decreased\n- Substance P and neuronal nitric oxide synthase (nNOS) changes varied by dose and by which nerve plexus was examined\n- Histological damage was dose-dependent: higher doses (1 g/day) caused more severe villus injury, cellular debris accumulation, mucus buildup, eosinophil infiltration, and hyperemia (excess blood flow)\n\nThese neurochemical changes suggest that microplastics can alter the function of the enteric nervous system — the 'second brain' that controls gut motility, secretion, and blood flow.","whyItMatters":"Humans are exposed to microplastics daily through food, water, and air. The gut's nervous system — containing as many neurons as the spinal cord — controls critical digestive functions through neuropeptide signaling. If microplastics disrupt this system, the implications could extend far beyond the gut, potentially affecting appetite, immune function, pain perception, and the gut-brain axis. This pig model is particularly relevant because pig digestive systems closely resemble those of humans.","specificNumbers":"","methodology":"Fifteen pigs were divided into three groups: control, low dose (0.1 g PET microplastics/day), and high dose (1 g/day), administered orally for 28 days. Jejunum tissue samples were collected and analyzed using immunofluorescence to identify and quantify neurons positive for specific neurotransmitters and neuropeptides (substance P, VIP, galanin, nNOS, CART, vesicular acetylcholine transporter). Histological examination assessed structural changes in the intestinal wall.","limitations":"The study used only 15 pigs (5 per group), which is a small sample for detecting subtle dose-response relationships. The microplastic doses, while designed to approximate human exposure, may not perfectly represent real-world conditions where exposure involves mixed plastic types over a lifetime. The 28-day exposure period may be too short to reveal chronic effects. The study documented neuronal changes but did not measure functional outcomes like gut motility or secretion."},{"rthcId":"RPEP-08256","title":"Slowing the Progression of Chronic Kidney Disease in Patients with Type 2 Diabetes Using Four Pillars of Therapy: The Time to Act is Now.","authors":"Georgianos, Panagiotis I; Vaios, Vasilios; Koufakis, Theocharis; Liakopoulos, Vassilios","year":2024,"journal":"Drugs, 84(11), 1337-1346","doi":"10.1007/s40265-024-02091-8","pmid":"39259460","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08257","title":"Cell-Penetrating and Enzyme-Responsive Peptides for Targeted Cancer Therapy: Role of Arginine Residue Length on Cell Penetration and In Vivo Systemic Toxicity.","authors":"Ghaemi, Behnaz; Tanwar, Swati; Singh, Aruna; Arifin, Dian R; McMahon, Michael T; Barman, Ishan; Bulte, Jeff W M","year":2024,"journal":"ACS applied materials & interfaces, 16(9), 11159-11171","doi":"10.1021/acsami.3c14908","pmid":"38385360","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08258","title":"The Roadmap of Plant Antimicrobial Peptides Under Environmental Stress: From Farm to Bedside.","authors":"Ghanbarzadeh, Zohreh; Mohagheghzadeh, Abdolali; Hemmati, Shiva","year":2024,"journal":"Probiotics and antimicrobial proteins, 16(6), 2269-2304","doi":"10.1007/s12602-024-10354-9","pmid":"39225894","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08259","title":"Bioactive and health-promoting properties of enzymatic hydrolysates of legume proteins: a review.","authors":"Gharibzahedi, Seyed Mohammad Taghi; Smith, Brennan; Altintas, Zeynep","year":2024,"journal":"Critical reviews in food science and nutrition, 64(9), 2548-2578","doi":"10.1080/10408398.2022.2124399","pmid":"36200775","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08260","title":"Improving migraine headache characteristics with high dose of thiamine: A randomized double-blind controlled trial.","authors":"Ghods, Maryam; Togha, Mansoureh; Jafari, Elham; Noormohammadi, Morvarid; Salami, Zhale; Nilghaz, Maryam; Narimani, Behnaz; Shafiee, Mahshad; Tabesh, Mahdieh; Razeghi-Jahromi, Soodeh","year":2024,"journal":"Current journal of neurology, 23(4), 208-216","doi":"10.18502/cjn.v23i4.18763","pmid":"41280350","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08261","title":"Boronic Acid-Linked Cell-Penetrating Peptide for Protein Delivery.","authors":"Ghosh, Pritam","year":2024,"journal":"ACS omega, 9(17), 19051-19056","doi":"10.1021/acsomega.3c09689","pmid":"38708278","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08262","title":"Glucagon-like Receptor-1 agonists for obesity: Weight loss outcomes, tolerability, side effects, and risks.","authors":"Ghusn, Wissam; Hurtado, Maria D","year":2024,"journal":"Obesity pillars, 12, 100127","doi":"10.1016/j.obpill.2024.100127","pmid":"39286601","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08263","title":"Role of lifestyle and glucagon-like peptide-1 receptor agonists for weight loss in obesity, type 2 diabetes and steatotic liver diseases.","authors":"Giannakogeorgou, Anna; Roden, Michael","year":2024,"journal":"Alimentary pharmacology & therapeutics, 59 Suppl 1, S52-S75","doi":"10.1111/apt.17848","pmid":"38813830","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08264","title":"Beneficial Effects of Multi-Micronutrient Supplementation with Collagen Peptides on Global Wrinkles, Skin Elasticity and Appearance in Healthy Female Subjects.","authors":"Gibson, Rachael; Krug, Lieselotte; Ramsey, David L; Safaei, Azadeh; Aspley, Sue","year":2024,"journal":"Dermatology and therapy, 14(6), 1599-1614","doi":"10.1007/s13555-024-01184-2","pmid":"38811471","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08265","title":"Effect of semaglutide on weight loss and glycaemic control in patients with Prader-Willi Syndrome and type 2 diabetes.","authors":"Giménez-Palop, Olga; Romero, Ana; Casamitjana, Laia; Pareja, Rocio; Rigla, Mercedes; Caixàs, Assumpta","year":2024,"journal":"Endocrinologia, diabetes y nutricion, 71(2), 83-87","doi":"10.1016/j.endien.2023.12.001","pmid":"38553173","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08266","title":"The Impact of Natriuretic Peptides on Heart Development, Homeostasis, and Disease.","authors":"Giovou, Alexandra E; Gladka, Monika M; Christoffels, Vincent M","year":2024,"journal":"Cells, 13(11)","doi":"10.3390/cells13110931","pmid":"38891063","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08267","title":"Semaglutide as a promising treatment for hypothalamic obesity: a six-month case series on four females with craniopharyngioma.","authors":"Gjersdal, Erlend; Larsen, Liva Bundgaard; Ettrup, Kåre Schmidt; Vestergaard, Peter; Nielsen, Eigil Husted; Karmisholt, Jesper Scott; Müller, Hermann L; Dal, Jakob","year":2024,"journal":"Pituitary, 27(5), 723-730","doi":"10.1007/s11102-024-01426-8","pmid":"39088138","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08268","title":"Real-world persistence and adherence to glucagon-like peptide-1 receptor agonists among obese commercially insured adults without diabetes.","authors":"Gleason, Patrick P; Urick, Benjamin Y; Marshall, Landon Z; Friedlander, Nicholas; Qiu, Yang; Leslie, R Scott","year":2024,"journal":"Journal of managed care & specialty pharmacy, 30(8), 860-867","doi":"10.18553/jmcp.2024.23332","pmid":"38717042","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08269","title":"Head-to-Head Comparison of Caco-2 Transwell and Gut-on-a-Chip Models for Assessing Oral Peptide Formulations.","authors":"Gleeson, John P; Zhang, Stephanie Y; Subelzu, Natalia; Ling, Jing; Nissley, Becky; Ong, Whitney; Nofsinger, Rebecca; Kesisoglou, Filippos","year":2024,"journal":"Molecular pharmaceutics, 21(8), 3880-3888","doi":"10.1021/acs.molpharmaceut.4c00210","pmid":"38941485","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08270","title":"GLP-1 and its derived peptides mediate pain relief through direct TRPV1 inhibition without affecting thermoregulation.","authors":"Go, Eun Jin; Hwang, Sung-Min; Jo, Hyunjung; Rahman, Md Mahbubur; Park, Jaeik; Lee, Ji Yeon; Jo, Youn Yi; Lee, Byung-Gil; Jung, YunJae; Berta, Temugin; Kim, Yong Ho; Park, Chul-Kyu","year":2024,"journal":"Experimental & molecular medicine, 56(11), 2449-2464","doi":"10.1038/s12276-024-01342-8","pmid":"39482537","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08271","title":"Oral glucagon-like peptide-1 receptor agonists and combinations of entero-pancreatic hormones as treatments for adults with type 2 diabetes: where are we now?","authors":"Gogineni, Prathima; Melson, Eka; Papamargaritis, Dimitris; Davies, Melanie","year":2024,"journal":"Expert opinion on pharmacotherapy, 25(7), 801-818","doi":"10.1080/14656566.2024.2356254","pmid":"38753454","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08272","title":"Anti-obesity pharmacological agents for polycystic ovary syndrome: A systematic review and meta-analysis to inform the 2023 international evidence-based guideline.","authors":"Goldberg, Alyse; Graca, Sandro; Liu, Jing; Rao, Vibhuti; Witchel, Selma Feldman; Pena, Alexia; Li, Rong; Mousa, Aya; Tay, Chau Thien; Pattuwage, Loyal; Teede, Helena; Yildiz, Bulent O; Ee, Carolyn","year":2024,"journal":"Obesity reviews : an official journal of the International Association for the Study of Obesity, 25(5), e13704","doi":"10.1111/obr.13704","pmid":"38355887","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"From 11 trials (545 intervention, 451 control participants, 12 comparisons), most anti-obesity agents improved anthropometric outcomes. Liraglutide, semaglutide, and orlistat appeared superior to placebo. Meta-analysis of exenatide vs metformin found no differences for anthropometric, hyperandrogenism, or metabolic outcomes, except metformin showed slightly lower fasting glucose (MD: 0.10 mmol/L, CI 0.02-0.17, I²=18%). Orlistat + COCP did not improve metabolic outcomes versus COCP alone (fasting insulin MD: -8.65 pmol/L, -33.55 to 16.26, I²=67%). The critical finding is the extreme paucity of evidence for a condition affecting 6-12% of reproductive-age women.","whyItMatters":"This review directly informed international clinical guidelines for PCOS, the most common endocrine disorder in reproductive-age women. The finding that powerful new drugs like semaglutide have barely been studied in PCOS — despite the condition's strong link to obesity — highlights a major gap in women's health research. It calls for urgent clinical trials of GLP-1 agonists specifically in PCOS populations.","specificNumbers":"","methodology":"Systematic review and meta-analysis searching Medline, EMBASE, PsycInfo, and CINAHL through July 2022 with a 10-year limit to focus on newer agents. Evaluated efficacy of anti-obesity agents for hormonal, reproductive, metabolic, and psychological outcomes in PCOS. Meta-analyses were possible for only two comparisons due to limited data. Conducted to inform the 2023 International Evidence-based Guideline on PCOS.","limitations":"Only 11 trials were identified, severely limiting the evidence. Meta-analysis was possible for only two comparisons. The search had a 10-year limit, potentially missing earlier relevant studies. Most included studies were small. Newer agents (semaglutide, tirzepatide) had minimal representation. Long-term outcomes, fertility effects, and psychological outcomes were inadequately studied. The review's search ended July 2022, predating recent semaglutide expansion."},{"rthcId":"RPEP-08273","title":"Peptide-based drug discovery through artificial intelligence: towards an autonomous design of therapeutic peptides.","authors":"Goles, Montserrat; Daza, Anamaría; Cabas-Mora, Gabriel; Sarmiento-Varón, Lindybeth; Sepúlveda-Yañez, Julieta; Anvari-Kazemabad, Hoda; Davari, Mehdi D; Uribe-Paredes, Roberto; Olivera-Nappa, Álvaro; Navarrete, Marcelo A; Medina-Ortiz, David","year":2024,"journal":"Briefings in bioinformatics, 25(4)","doi":"10.1093/bib/bbae275","pmid":"38856172","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"AI is transforming peptide drug discovery through three key approaches: classifier methods that predict peptide properties (antimicrobial, antitumor, etc.), predictive systems that estimate stability and bioavailability, and deep-generative models (GANs and variational autoencoders) that design entirely new peptide sequences. The authors propose a comprehensive AI-assisted pipeline from peptide design through validation. Key challenges remain: optimization of processing, careful validation of predictive models, and bridging the gap between computationally designed peptides and experimental confirmation.","whyItMatters":"Traditional peptide drug discovery is slow and expensive — testing thousands of candidates to find one that works. AI can dramatically accelerate this by predicting which peptide sequences will have desired properties before they're ever synthesized. Deep-generative models can even design novel peptides that don't exist in nature, potentially creating therapeutic molecules that overcome the limitations of natural peptides like short half-life and poor oral bioavailability.","specificNumbers":"","methodology":"This is a perspective/review article that surveys the current landscape of AI methods applied to peptide drug discovery. The authors review machine learning classifiers, predictive models, generative AI approaches (GANs, variational autoencoders), existing databases, and propose a comprehensive pipeline for AI-assisted peptide design and validation.","limitations":"As a perspective article, no original data is presented. The AI-designed peptides discussed often lack experimental validation. Generative models can propose biologically implausible sequences. The gap between computational prediction and real-world therapeutic efficacy remains substantial. Bias in training datasets can limit the diversity and novelty of AI-generated peptides."},{"rthcId":"RPEP-08274","title":"Antihypertensive treatment of end-stage renal disease patients on hemodialysis does not alter circulating ACE and ACE2 activity and angiotensin peptides.","authors":"Gomes, Renata Vitoriano Corradi; Peluso, A Augusto; Ronchi, Fernanda Aparecida; de Oliveira, Lilian Caroline Gonçalves; Casarini, Dulce Elena; Santos, Robson Augusto Souza; Endlich, Patrick Wander; de Abreu, Glaucia Rodrigues","year":2024,"journal":"The American journal of the medical sciences, 367(2), 128-134","doi":"10.1016/j.amjms.2023.11.014","pmid":"37984736","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08275","title":"Antifungal peptides from living organisms.","authors":"Gong, Yi; Xue, Qunhang; Li, Jun; Zhang, Shicui","year":2024,"journal":"Frontiers in microbiology, 15, 1511461","doi":"10.3389/fmicb.2024.1511461","pmid":"39741586","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08276","title":"Successful Implementation of a Multidisciplinary Weight Loss Program Including GLP1 Receptor Agonists for Liver Transplant Candidates With High Body Mass Index.","authors":"Gonzalez, Humberto C; Myers, Daniel T; Venkat, Deepak","year":2024,"journal":"Transplantation, 108(11), 2233-2237","doi":"10.1097/TP.0000000000005070","pmid":"39466197","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Of 19 patients with high BMI referred to a multidisciplinary liver metabolic clinic, median weight loss was 11.7 kg (range 0–33 kg). Fifteen patients were treated with a GLP-1 receptor agonist (6 with liraglutide, 8 with semaglutide, 1 with tirzepatide) and 4 received phentermine. Eight patients (42%) ultimately received a liver transplant and 4 more were waitlisted. The median time from baseline to waitlisting was approximately 5.5 months (166 days). Eighty-four percent of patients had metabolic dysfunction-associated steatohepatitis as the underlying liver condition.","whyItMatters":"Patients with BMI over 40 are often considered ineligible for liver transplant, yet there is little guidance on how to help them lose enough weight to qualify. This study demonstrates that a structured, multidisciplinary program incorporating GLP-1 receptor agonists can help these critically ill patients achieve meaningful weight loss and gain access to life-saving transplantation.","specificNumbers":"n=19 · median BMI 42 · median weight loss 11.7 kg · 84% had MASH · 8 patients transplanted · 4 more waitlisted · median 166 days to waitlisting · 15 treated with GLP-1 RA","methodology":"Retrospective review of 19 patients aged 18 or older referred to the Henry Ford Health Liver Metabolic Clinic from August 2019 to September 2023 with BMI above 40 or above 35 with abdominal adiposity complicating surgery. Patients received individualized support from hepatologists, dieticians, and counselors, along with anti-obesity medications including GLP-1 receptor agonists or phentermine.","limitations":"This was a small, single-center retrospective study with only 19 patients and no control group, making it impossible to determine how much of the weight loss was attributable to the GLP-1 receptor agonists versus the dietary and counseling support. Four patients died during follow-up from progressive liver disease or infection, highlighting the fragility of this population."},{"rthcId":"RPEP-08277","title":"Differential Effects of Type 2 Diabetes Treatment Regimens on Diabetes Distress and Depressive Symptoms in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE).","authors":"Gonzalez, Jeffrey S; Bebu, Ionut; Krause-Steinrauf, Heidi; Hoogendoorn, Claire J; Crespo-Ramos, Gladys; Presley, Caroline; Naik, Aanand D; Kuo, Shihchen; Johnson, Mary L; Wexler, Deborah; Crandall, Jill P; Bantle, Anne E; Arends, Valerie; Cherrington, Andrea L","year":2024,"journal":"Diabetes care, 47(4), 610-619","doi":"10.2337/dc23-2459","pmid":"38416773","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 1,739 GRADE trial participants randomized to add insulin glargine, glimepiride, liraglutide, or sitagliptin to metformin:\n\nAt 1 year:\n- All treatments reduced diabetes distress (-0.24, P < 0.0001) and depressive symptoms (-0.67, P < 0.0001)\n- Insulin glargine showed lower diabetes distress than other groups combined (-0.10, P = 0.002)\n- Liraglutide showed lower diabetes distress than glimepiride or sitagliptin (-0.10, P = 0.008)\n\nOver 3-year follow-up:\n- No significant differences in total diabetes distress between groups\n- Interpersonal diabetes distress remained lower for liraglutide\n- No significant differences in depressive symptoms between any groups\n\nKey conclusion: Contrary to expectations, basal insulin did NOT increase emotional distress.","whyItMatters":"Fear of injections and concerns about treatment burden are major barriers to diabetes medication adherence. Many patients resist starting insulin or injectable GLP-1 drugs because they worry about the psychological impact. This large randomized trial provides reassuring evidence: injectable treatments didn't worsen emotional health, and liraglutide actually improved it. For clinicians, these findings can help overcome patient resistance to effective injectable therapies and support shared decision-making about treatment options.","specificNumbers":"","methodology":"Emotional Distress Substudy of the GRADE (Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study) trial. 1,739 adults with T2DM <10 years' duration on metformin monotherapy were randomized to add insulin glargine, glimepiride, liraglutide, or sitagliptin. Diabetes distress and depressive symptoms were assessed every 6 months for 3 years using validated instruments. Analyses compared groups at 1 year and over the full follow-up.","limitations":"The emotional distress substudy enrolled 1,739 of the larger GRADE trial's participants, introducing potential selection bias. The -0.10 point differences, while statistically significant, are modest in clinical terms. The study population (mean age 58, majority non-Hispanic White) may not represent all T2DM patients. Depression was mild overall, so effects might differ in populations with higher baseline depression. Blinding was not possible due to the different administration routes, which could influence psychological outcomes."},{"rthcId":"RPEP-08278","title":"Participation of kisspeptin, progesterone, and GnRH receptors on lordosis behavior induced by kisspeptin.","authors":"González-Flores, Oscar; Domínguez-Ordóñez, Raymundo; Delgado-Macuil, Raul Jacobo; Tlachi-López, José Luis; Luna-Hernández, Ailyn; Montes-Narváez, Omar; Pfaus, James G; García-Juárez, Marcos","year":2024,"journal":"Physiology & behavior, 283, 114609","doi":"10.1016/j.physbeh.2024.114609","pmid":"38851441","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08279","title":"Angiotensin converting enzyme inhibitory hydrolysate and peptide fractions from chicken skin collagen, as modulators of lipid accumulation in adipocytes 3 T3-L1, after in vitro gastrointestinal digestion.","authors":"González-Noriega, Julio Alfonso; Valenzuela-Melendres, Martín; Hernández-Mendoza, Adrián; Astiazarán-García, Humberto; Islava-Lagarda, Thalia; Tortoledo-Ortiz, Orlando; Huerta-Ocampo, José Ángel; de La Garza, Ana Laura; Peña-Ramos, Etna Aída","year":2024,"journal":"Food chemistry, 460(Pt 2), 140551","doi":"10.1016/j.foodchem.2024.140551","pmid":"39083965","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Chicken skin collagen hydrolysate peptide fraction F4 and its digested form (DF4) showed strong ACE-inhibitory activity with IC50 values of 188.84 and 220.03 μg/mL, respectively — approximately 2-fold more potent than the smaller peptide fraction from post-digested hydrolysate (FDH, IC50 388.57 μg/mL).\n\nFor anti-obesity effects, DF4 at 800 μg/mL reduced lipid accumulation by 83% in preadipocytes. In differentiated adipocytes, both FDH and DF4 achieved 45–60% lipid reduction regardless of concentration. Nine peptides were identified as potential ACE inhibitors in the active fractions.","whyItMatters":"This research demonstrates that food-industry waste products (chicken skin) can be converted into bioactive peptides with dual health benefits — blood pressure management and anti-obesity effects. If these peptide fractions survive digestion and maintain activity, they could potentially be developed into functional food ingredients or nutraceutical supplements, adding value to poultry processing byproducts while addressing hypertension and obesity.","specificNumbers":"","methodology":"Chicken skin collagen was enzymatically hydrolyzed to produce peptide fractions of different molecular weights. These fractions were tested for ACE-inhibitory activity before and after simulated in vitro gastrointestinal digestion. The fractions were also tested on 3T3-L1 adipocytes (a standard fat cell model) to measure their effect on lipid accumulation in both preadipocytes and differentiated fat cells. Mass spectrometry was used to identify individual peptides in the most active fractions.","limitations":"This is entirely an in vitro study — results from cell culture and simulated digestion cannot predict effects in living organisms. The 3T3-L1 cell line is a mouse model that may not perfectly represent human fat cell behavior. In vivo bioavailability of these peptides after oral consumption is unknown. The abstract contains what appears to be a formatting error in the IC50 comparison, making some specific numbers difficult to interpret precisely. No animal or human studies were conducted."},{"rthcId":"RPEP-08280","title":"Are the cardiovascular properties of GLP-1 receptor agonists differentially modulated by sulfonylureas? Insights from post-hoc analysis of EXSCEL.","authors":"Gooding, Kim M; Stevens, Susanna; Lokhnygina, Yuliya; Giczewska, Anna; Shore, Angela C; Holman, Rury R","year":2024,"journal":"Diabetes research and clinical practice, 212, 111685","doi":"10.1016/j.diabres.2024.111685","pmid":"38670496","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08281","title":"Anti-Hyperglycemic Medication Management in the Perioperative Setting: A Review and Illustrative Case of an Adverse Effect of GLP-1 Receptor Agonist.","authors":"Goron, Abby R; Connolly, Courtney; Valdez-Sinon, Arielle N; Hesson, Ashley; Helou, Christine; Kirschen, Gregory W","year":2024,"journal":"Journal of clinical medicine, 13(20)","doi":"10.3390/jcm13206259","pmid":"39458209","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08282","title":"Utilising Health Technology Assessment to Develop Managed Access Protocols to Facilitate Drug Reimbursement in Ireland.","authors":"Gorry, Claire; Daly, Maria; Barrett, Rosealeen; Finnigan, Karen; Smith, Amelia; Doran, Stephen; Duggan, Bernard; Clarke, Sarah; Barry, Michael","year":2024,"journal":"Applied health economics and health policy, 22(6), 771-781","doi":"10.1007/s40258-024-00904-1","pmid":"39133443","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08283","title":"Epidemiology of heart failure presentations to United States emergency departments from 2016 to 2023.","authors":"Gottlieb, Michael; Moyer, Eric; Bernard, Kyle","year":2024,"journal":"The American journal of emergency medicine, 86, 70-73","doi":"10.1016/j.ajem.2024.09.059","pmid":"39366035","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08284","title":"Lipid-Induced Oxidative Modifications Decrease the Bioactivities of Collagen Hydrolysates from Fish Skin: The Underlying Mechanism Based on the Proteomic Strategy.","authors":"Gou, Fengjie; Gao, Song; Li, Bo","year":2024,"journal":"Foods (Basel, Switzerland), 13(4)","doi":"10.3390/foods13040583","pmid":"38397560","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08285","title":"Glucose-Lowering Agents Developed in the Last Two Decades and Their Perioperative Implications.","authors":"Goudra, Basavana; Merli, Geno J; Green, Michael","year":2024,"journal":"Pharmaceuticals (Basel, Switzerland), 18(1)","doi":"10.3390/ph18010004","pmid":"39861067","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08286","title":"Association between glucagon-like peptide-1 receptor agonist use and progression of monoclonal gammopathy of uncertain significance to multiple myeloma among patients with diabetes.","authors":"Grandhi, Nikhil; Liu, Lawrence; Wang, Mei; Thomas, Theodore; Schoen, Martin; Sanfilippo, Kristen; Gao, Feng; Colditz, Graham A; Carson, Kenneth R; Janakiram, Murali; Chang, Su-Hsin","year":2024,"journal":"JNCI cancer spectrum, 8(6)","doi":"10.1093/jncics/pkae095","pmid":"39514091","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In a matched cohort of 3,291 veterans with diabetes and MGUS (1,097 GLP-1 RA users matched to 2,194 non-users):\n\n- Progression to multiple myeloma: 2.6% in GLP-1 RA users vs. 5.0% in non-users\n- Cumulative incidence was significantly different (P = 0.02)\n- GLP-1 RA use was associated with a 55% reduction in myeloma progression (HR = 0.45, 95% CI 0.22–0.93, P = 0.03)\n\nThe analysis accounted for the competing risk of death and used a validated NLP algorithm to confirm MGUS diagnosis and progression.","whyItMatters":"MGUS affects about 3% of people over 50, and there are currently no approved drugs to prevent its progression to myeloma. If GLP-1 receptor agonists truly slow this progression, it could benefit thousands of people already taking these drugs for diabetes or obesity, and might change how MGUS is managed clinically.","specificNumbers":"","methodology":"Population-based cohort study of US veterans diagnosed with MGUS from 2006 to 2021 who also had diabetes. A validated natural language processing algorithm confirmed MGUS and myeloma progression. Researchers performed 1:2 matching of GLP-1 RA users to non-users and used Fine-Gray competing risk models with death as a competing event to estimate the association.","limitations":"This is an observational study that cannot prove causation. Despite matching, residual confounding is possible — healthier patients may be more likely to receive newer, more expensive GLP-1 RAs. The study population is predominantly male veterans, limiting generalizability. The number of progression events was small (absolute numbers not detailed), making the confidence interval wide. The mechanism by which GLP-1 RAs might prevent myeloma progression is unknown."},{"rthcId":"RPEP-08287","title":"A Specific Collagen Hydrolysate Improves Postprandial Glucose Tolerance in Normoglycemic and Prediabetic Mice and in a First Proof of Concept Study in Healthy, Normoglycemic and Prediabetic Humans.","authors":"Grasset, Estelle; Briand, François; Virgilio, Nicolina; Schön, Christiane; Wilhelm, Manfred; Cudennec, Benoit; Ravallec, Rozenn; Aboubacar, Hairati; Vleminckx, Sara; Prawitt, Janne; Sulpice, Thierry; Gevaert, Elien","year":2024,"journal":"Food science & nutrition, 12(11), 9607-9620","doi":"10.1002/fsn3.4538","pmid":"39619994","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The collagen hydrolysate H80 (Nextida GC) demonstrated GLP-1-mediated metabolic improvements:\n\n**In mice:**\n- Blood glucose response reduced by 25% in lean and 36% in prediabetic mice at 4 g/kg\n- Plasma active GLP-1 increased by 217% in lean and 860% in prediabetic mice\n- Gastric emptying slowed by 60% after 21 days of supplementation\n- Plasma insulin increased by 166% after 35 days of supplementation\n\n**In humans (proof of concept):**\n- A 5 g oral dose of H80 reduced postprandial glucose response in healthy, normoglycemic, and prediabetic participants\n\nThe mechanism appears to work through stimulating natural GLP-1 secretion from intestinal L-cells, mimicking the physiological pathway that GLP-1 receptor agonist drugs target pharmacologically.","whyItMatters":"GLP-1 receptor agonists like semaglutide are expensive injectable drugs with supply constraints. If a simple oral collagen peptide supplement can meaningfully boost the body's own GLP-1 production and improve glucose tolerance, it could offer an accessible, affordable complement to pharmaceutical approaches — particularly for the hundreds of millions of people with prediabetes who might not yet qualify for prescription drugs but could benefit from improved glucose regulation.","specificNumbers":"","methodology":"Collagen hydrolysates were screened in vitro for GLP-1-stimulating ability. The best candidate (H80) was tested in lean normoglycemic mice (acute oral glucose challenge 45 minutes after dosing) and overweight prediabetic mice (6 weeks daily supplementation with acute challenges at days 21 and 34). Oral glucose tolerance, plasma insulin, GLP-1 levels, and gastric emptying were measured. A small human proof-of-concept study also evaluated postprandial glucose response at a 5 g dose.","limitations":"The human proof-of-concept study is described as small, with no specific participant numbers or statistical details provided in the abstract. The mouse doses (4 g/kg) are very high relative to the human dose (5 g total), and it's unclear whether the effects at human-practical doses will be clinically meaningful long-term. The study was industry-sponsored (the product has a brand name, Nextida GC), which may introduce bias. Long-term safety and efficacy data are lacking."},{"rthcId":"RPEP-08288","title":"Once-weekly semaglutide doubles the five-year risk of nonarteritic anterior ischemic optic neuropathy in a Danish cohort of 424,152 persons with type 2 diabetes.","authors":"Grauslund, Jakob; Taha, Andreas Abou; Molander, Laleh Dehghani; Kawasaki, Ryo; Möller, Sören; Højlund, Kurt; Stokholm, Lonny","year":2024,"journal":"International journal of retina and vitreous, 10(1), 97","doi":"10.1186/s40942-024-00620-x","pmid":"39696569","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08289","title":"Real-world effectiveness of Anti-CGRP monoclonal antibodies compared to OnabotulinumtoxinA (RAMO) in chronic migraine: a retrospective, observational, multicenter, cohort study.","authors":"Grazzi, Licia; Giossi, Riccardo; Montisano, Danilo Antonio; Canella, Mattia; Marcosano, Marilena; Altamura, Claudia; Vernieri, Fabrizio","year":2024,"journal":"The journal of headache and pain, 25(1), 14","doi":"10.1186/s10194-024-01721-6","pmid":"38308209","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08290","title":"Effect of glucagon like peptide-1 receptor agonist exenatide, used as an intracranial pressure lowering agent, on cognition in Idiopathic Intracranial Hypertension.","authors":"Grech, Olivia; Mitchell, James L; Lyons, Hannah S; Yiangou, Andreas; Thaller, Mark; Tsermoulas, Georgios; Brock, Kristian; Mollan, Susan P; Sinclair, Alexandra J","year":2024,"journal":"Eye (London, England), 38(7), 1374-1379","doi":"10.1038/s41433-023-02908-y","pmid":"38212401","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In women with idiopathic intracranial hypertension (IIH), exenatide (a GLP-1 receptor agonist) did not compromise cognition over 12 weeks compared to placebo. Patients treated with exenatide showed significant improvements in fluid intelligence (T-score 38.4→52.9, p=0.0005), processing speed (43.7→58.4, p=0.0058), and episodic memory (49.4→62.1, p=0.0315). Baseline cognitive impairment was confirmed in fluid intelligence, attention, and executive function (all T-scores well below population mean of 50).","whyItMatters":"IIH patients suffer cognitive impairment from raised intracranial pressure, and current medications often worsen thinking problems as a side effect. Exenatide both lowers intracranial pressure and appears to improve rather than harm cognition — a potential game-changer for IIH treatment and another example of GLP-1 peptide drugs showing unexpected brain benefits.","specificNumbers":"n=15 (7 exenatide, 8 placebo) · 12 weeks · fluid intelligence improved 38.4→52.9 (p=0.0005) · processing speed 43.7→58.4 (p=0.0058) · episodic memory 49.4→62.1 (p=0.0315) · T-score 50 = population mean","methodology":"Exploratory analysis from the IIH:Pressure randomized trial. 15 women with IIH and implanted telemetric ICP monitors were randomized to exenatide (n=7) or placebo (n=8) for 12 weeks. Cognition was assessed at baseline and 12 weeks using the NIH Toolbox Cognitive Battery, measuring fluid intelligence, attention, executive function, processing speed, and episodic memory.","limitations":"Very small sample (n=15, only 7 on exenatide). Exploratory analysis — not the primary endpoint of the trial. No correction for multiple comparisons. All female participants. Practice effects from repeat cognitive testing could contribute to improvements. Cannot determine if cognitive improvements were from direct brain effects of exenatide or secondary to ICP reduction."},{"rthcId":"RPEP-08291","title":"Intranasal zavegepant for the acute treatment of migraine.","authors":"Greco, Guy; Monteith, Teshamae","year":2024,"journal":"Expert review of neurotherapeutics, 24(12), 1131-1140","doi":"10.1080/14737175.2024.2405741","pmid":"39314003","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08292","title":"Effects of the Dual FAAH/MAGL Inhibitor AKU-005 on Trigeminal Hyperalgesia in Male Rats.","authors":"Greco, Rosaria; Demartini, Chiara; Francavilla, Miriam; Zanaboni, Anna Maria; Facchetti, Sara; Palmisani, Michela; Franco, Valentina; Tassorelli, Cristina","year":2024,"journal":"Cells, 13(10)","doi":"10.3390/cells13100830","pmid":"38786051","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08293","title":"Intranasal administration of recombinant human BDNF as a potential therapy for some primary headaches.","authors":"Greco, Rosaria; Francavilla, Miriam; Facchetti, Sara; Demartini, Chiara; Zanaboni, Anna Maria; Antonangeli, Maria Irene; Maffei, Mariano; Cattani, Franca; Aramini, Andrea; Allegretti, Marcello; Tassorelli, Cristina; De Filippis, Lidia","year":2024,"journal":"The journal of headache and pain, 25(1), 184","doi":"10.1186/s10194-024-01890-4","pmid":"39455939","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08294","title":"Effects of an herbal adaptogen feed-additive on feeding-related hypothalamic neuropeptides in chronic cyclic heat-stressed chickens.","authors":"Greene, Elizabeth S; Ardakani, Maryam Afkhami; Dridi, Sami","year":2024,"journal":"Neuropeptides, 106, 102439","doi":"10.1016/j.npep.2024.102439","pmid":"38788297","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08295","title":"Repeat Peptide Receptor Radionuclide Therapy in Neuroendocrine Tumors: A NET Center of Excellence Experience.","authors":"Grewal, Udhayvir S; Loeffler, Bradley T; Paschke, Alexander; Dillon, Joseph S; Chandrasekharan, Chandrikha","year":2024,"journal":"Journal of gastrointestinal cancer, 55(3), 1165-1170","doi":"10.1007/s12029-024-01065-z","pmid":"38780680","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 11 neuroendocrine tumor patients who received repeat PRRT after disease progression:\n\nEfficacy after PRRT2 (at first restaging, 3-6 months):\n- Partial response: 18.2% (2/11)\n- Stable disease: 36.4% (4/11)\n- Progressive disease: 27.3% (3/11)\n- Died before restaging: 18.2% (2/11)\n- Overall disease control rate: 54.5% (6/11)\n\nProgression-free survival:\n- PRRT1: 25.4 months median PFS\n- PRRT2: 13.1 months median PFS\n- Difference statistically significant (P = 0.0001)\n\nSafety: No significant difference in hematological or renal toxicity rates between PRRT1 and PRRT2.","whyItMatters":"Neuroendocrine tumors are rare cancers with limited treatment options. PRRT is one of the most effective therapies, using peptides to deliver radiation precisely to tumor cells. When patients progress after initial PRRT, clinicians face a difficult decision: is it safe and worthwhile to repeat? Most data comes from European centers, so this US experience fills an important evidence gap. The finding that repeat PRRT is safe and provides disease control in over half of patients gives clinicians a treatment option for this otherwise limited situation.","specificNumbers":"","methodology":"Retrospective single-center study using a longitudinal NET registry at a US NET center of excellence. 11 patients who received initial PRRT (either 177Lu-DOTATATE or 90Y-DOTATOC) followed by repeat PRRT after radiographic progression were identified. Patient, tumor, and treatment characteristics were reviewed. Objective response rates were assessed at first restaging (3-6 months). Short and long-term hematological and renal toxicities were compared between PRRT1 and PRRT2.","limitations":"Very small sample size (n=11) severely limits the reliability of response rates and toxicity comparisons. Retrospective single-center design introduces selection bias. Different PRRT agents (177Lu-DOTATATE vs 90Y-DOTATOC) were used across patients, complicating comparisons. Two patients died before first restaging, which significantly affects the small-sample response calculations. The study cannot determine whether repeat PRRT extends overall survival compared to alternative treatments."},{"rthcId":"RPEP-08296","title":"Real-World HbA1c Changes Among Type 2 Diabetes Mellitus Patients Initiating Treatment With a 1.0 Mg Weekly Dose of Semaglutide for Diabetes.","authors":"Gronroos, Noelle N; Swift, Caroline; Frazer, Monica S; Sargent, Andrew; Leszko, Michael; Buysman, Erin; Alvarez, Sara; Dunn, Tyler J; Noone, Josh","year":2024,"journal":"Journal of health economics and outcomes research, 11(2), 118-124","doi":"10.36469/001c.124111","pmid":"39507603","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 2,168 patients with T2D and baseline HbA1c ≥7% who initiated once-weekly semaglutide 1.0 mg, the mean HbA1c reduction was 1.2% (p<0.001). Similar reductions were observed in the persistent patient subgroup (those with at least 90 days of continuous treatment).\n\nThe patient population was notably medically complex: patients were taking an average of 13.5 different medication classes, and comorbidity rates were high — lipid metabolism disorder (90.8%), hypertension (86.6%), diabetes with complications (86.8%), and other metabolic disorders (72.5%). Despite this burden of disease, semaglutide consistently lowered blood sugar, confirming its effectiveness in the most challenging real-world patient populations.","whyItMatters":"Clinical trials select for healthier, more adherent patients — often excluding the complex, multi-morbid patients who make up most real-world diabetes care. This study demonstrates that semaglutide's blood sugar-lowering benefits are preserved in patients with extensive comorbidities and polypharmacy. For clinicians hesitating to prescribe semaglutide to their most complex patients, this data provides real-world reassurance.","specificNumbers":"","methodology":"Retrospective observational study using the Optum Research Database (US insurance claims). Adult patients with T2D and HbA1c ≥7% who initiated once-weekly semaglutide between January 2018 and December 2019 and were prescribed the 1.0 mg maintenance dose were included. Patients needed continuous health plan enrollment for 12 months before and after initiation. HbA1c change was calculated as the difference between the latest post-index and pre-index measurement. A subgroup analysis of persistent patients (≥90 days continuous treatment) was also performed.","limitations":"This is a retrospective study using insurance claims data, which may have coding inaccuracies and cannot capture all clinical variables (diet, exercise, adherence patterns). There was no control group, so the HbA1c reduction cannot be definitively attributed to semaglutide versus concurrent medication changes or lifestyle factors. Only patients on the 1.0 mg maintenance dose were included, excluding those on lower doses or who didn't reach maintenance. The 2018-2019 timeframe represents early semaglutide adoption and may not reflect current prescribing patterns."},{"rthcId":"RPEP-08297","title":"Discovery of Truncated Cyclic Peptides Targeting an Induced-Fit Pocket on PCSK9.","authors":"Grosche, Philipp; Flyer, Alec N; Gattlen, Raphael; Xu, Mei; Golosov, Andrei A; Vera, Victoria; Pickett, Stephanie; Brousseau, Margaret E; Chopra, Rajiv; Clairmont, Kevin B; Koch, Alexander; Liu, Eugene; Reid, Patrick; Perry, Lauren; Yang, Lihua; Yang, Qing; Monovich, Lauren G","year":2024,"journal":"ChemMedChem, 19(23), e202400208","doi":"10.1002/cmdc.202400208","pmid":"39437016","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Starting from previously identified 13-amino acid cyclic peptides, the researchers used structure-based design to create truncated, electrically neutral versions that maintained full ability to disrupt the PCSK9/LDL-receptor protein-protein interaction in both biochemical and cellular assays.\n\nThe original larger peptides required charged chemical groups to function and lacked oral bioavailability in rodents — a major barrier to pill development. The new truncated versions eliminated this charge requirement.\n\nIn parallel, mRNA-peptide display screening identified novel 8- and 9-amino acid compounds that bind the same induced-fit pocket on PCSK9 but in a structurally distinct manner. Although these shorter peptides were not functionally active on their own, they demonstrate that smaller molecules can access this binding site, providing additional starting points for further optimization toward true small-molecule oral agents.","whyItMatters":"Current PCSK9 inhibitors (evolocumab, alirocumab) are injectable antibodies that dramatically lower cholesterol but require regular injections. An oral PCSK9 inhibitor would be transformative for the millions of patients who need cholesterol lowering but prefer pills over injections. This work demonstrates a viable path from peptide hits to smaller, oral-compatible molecules targeting a pocket on PCSK9 that was previously unknown.","specificNumbers":"","methodology":"The team used structure-based drug design to systematically modify their original 13-mer cyclic peptides, reducing size and removing charged groups while monitoring activity. Peptide variants were tested in biochemical assays measuring PCSK9/LDL-receptor binding disruption and in cellular assays. In parallel, mRNA-peptide display — a technique that screens billions of peptide sequences simultaneously — was used to discover new short peptides that bind the PCSK9 induced-fit pocket. Structural analysis was used to understand how different peptide classes interact with the target.","limitations":"The truncated peptides have not been tested for oral bioavailability — the key practical goal. The shorter 8-9 mer peptides identified by display screening were not functionally active, meaning further optimization is needed. No in vivo efficacy or pharmacokinetic data are reported for the new truncated compounds. The induced-fit pocket may behave differently across PCSK9 variants in diverse patient populations."},{"rthcId":"RPEP-08298","title":"Pregnancy outcomes among patients with complex congenital heart disease.","authors":"Gu, Jiaqi; Zhao, He; Zhang, Jun","year":2024,"journal":"NPJ cardiovascular health, 1(1)","doi":"10.1038/s44325-024-00022-w","pmid":"41776024","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08299","title":"Erythrocyte membrane-coated nanocarriers modified by TGN for Alzheimer's disease.","authors":"Gu, Jinlian; Yan, Chang; Yin, Shun; Wu, Hao; Liu, Chi; Xue, Ao; Lei, Xia; Zhang, Ning; Geng, Fang","year":2024,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 366, 448-459","doi":"10.1016/j.jconrel.2023.12.030","pmid":"38128884","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08300","title":"Prediction of blood-brain barrier penetrating peptides based on data augmentation with Augur.","authors":"Gu, Zhi-Feng; Hao, Yu-Duo; Wang, Tian-Yu; Cai, Pei-Ling; Zhang, Yang; Deng, Ke-Jun; Lin, Hao; Lv, Hao","year":2024,"journal":"BMC biology, 22(1), 86","doi":"10.1186/s12915-024-01883-4","pmid":"38637801","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08301","title":"Venomics AI: a computational exploration of global venoms for antibiotic discovery.","authors":"Guan, Changge; Torres, Marcelo D T; Li, Sufen; de la Fuente-Nunez, Cesar","year":2024,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2024.12.17.628923","pmid":"39764027","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"From 16,123 venom proteins, the APEX deep learning model generated 40,626,260 venom-encrypted peptides (VEPs) and identified 386 candidates structurally and functionally distinct from known antimicrobial peptides. These VEPs had high net charge and elevated hydrophobicity — properties that enable bacterial membrane disruption.\n\nOf 58 VEPs selected for experimental validation, 53 (91%) displayed potent antimicrobial activity. Structural studies showed the peptides adopt α-helical conformations in membrane-mimicking environments. Mechanistic assays confirmed they work by depolarizing bacterial membranes. In vivo, lead VEPs significantly reduced A. baumannii bacterial burdens in a mouse infection model without notable toxicity.","whyItMatters":"This study demonstrates a paradigm shift in antibiotic discovery: instead of the traditional approach of screening individual compounds one at a time, AI can rapidly search millions of peptide candidates from nature's existing chemical diversity. The 91% validation hit rate is extraordinary for drug discovery (typical hit rates are under 1%). Venom peptides have been shaped by millions of years of evolution to be potent and selective, making them an ideal starting library for AI-guided antibiotic development.","specificNumbers":"","methodology":"Comprehensive global venomics datasets were mined using machine learning. APEX, a deep learning model combining peptide-sequence encoding with neural networks, predicted antimicrobial activity from over 40 million computationally generated venom peptide fragments. Structural analysis included conformational studies in membrane-mimicking environments. Experimental validation tested 58 top candidates for antimicrobial activity, membrane depolarization, and in vivo efficacy in an A. baumannii mouse infection model.","limitations":"This is a preprint (bioRxiv), not yet peer-reviewed. The in vivo testing used a single bacterial species (A. baumannii) in an acute infection model; broader pathogen coverage and chronic infection models would strengthen the findings. The pharmacokinetics, stability, and manufacturing scalability of the lead VEPs are not discussed. The transition from mouse efficacy to human clinical trials involves substantial additional development. Cost of peptide antibiotic production compared to small-molecule antibiotics remains a practical challenge."},{"rthcId":"RPEP-08302","title":"Deficiency of leap2 promotes somatic growth in zebrafish: Involvement of the growth hormone system.","authors":"Guan, Kaiyu; Ye, Minjie; Guo, Anqi; Chen, Xiaoyu; Shan, Yunfeng; Li, Xi","year":2024,"journal":"Heliyon, 10(18), e36397","doi":"10.1016/j.heliyon.2024.e36397","pmid":"39347412","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08303","title":"Amide-to-Triazole Switch in Somatostatin-14-Based Radioligands: Impact on Receptor Affinity and In Vivo Stability.","authors":"Guarrochena, Xabier; Kanellopoulos, Panagiotis; Stingeder, Anna; Rečnik, Lisa-Maria; Feiner, Irene V J; Brandt, Marie; Kandioller, Wolfgang; Maina, Theodosia; Nock, Berthold A; Mindt, Thomas L","year":2024,"journal":"Pharmaceutics, 16(3)","doi":"10.3390/pharmaceutics16030392","pmid":"38543286","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08304","title":"Medications for Obesity: A Review.","authors":"Gudzune, Kimberly A; Kushner, Robert F","year":2024,"journal":"JAMA, 332(7), 571-584","doi":"10.1001/jama.2024.10816","pmid":"39037780","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08305","title":"Evaluation of the risk of hypertension in patients treated with anti-CGRP monoclonal antibodies in a real-life study.","authors":"Guerzoni, Simona; Castro, Flavia Lo; Brovia, Daria; Baraldi, Carlo; Pani, Luca","year":2024,"journal":"Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 45(4), 1661-1668","doi":"10.1007/s10072-023-07167-z","pmid":"37926748","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08306","title":"Exploring the association between suicidal thoughts, self-injury, and GLP-1 receptor agonists in weight loss treatments: Insights from pharmacovigilance measures and unmasking analysis.","authors":"Guirguis, A; Chiappini, S; Papanti P, G D; Vickers-Smith, R; Harris, D; Corkery, J M; Arillotta, D; Floresta, G; Martinotti, G; Schifano, F","year":2024,"journal":"European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 82, 82-91","doi":"10.1016/j.euroneuro.2024.02.003","pmid":"38508100","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 209,354 adverse drug reports in FAERS (2005-2023), 5,378 involved psychiatric disorders and 383 were classified as serious. After pharmacovigilance unmasking, 271 cases implicated individual GLP-1 RAs:\n- Liraglutide: n=90, ROR=1.64\n- Semaglutide: n=61, ROR=2.03\n- Exenatide: n=67, ROR=0.80\n- Dulaglutide: n=45, ROR=0.84\n- Tirzepatide: n=5, ROR=1.76\n\n42 deaths were recorded including 13 completed suicides. Suicidal ideation was reported for 6 of 7 GLP-1 RAs (all except lixisenatide). Critically, metformin had a greater association with these adverse events than GLP-1 drugs, while orlistat did not. No causal link could be established.","whyItMatters":"With GLP-1 drugs being prescribed to tens of millions of people for weight loss and diabetes, even rare psychiatric side effects could affect many patients. This comprehensive FAERS analysis provides the most detailed drug-by-drug breakdown of suicidality reports across GLP-1 agonists published to date. The finding that metformin actually has higher psychiatric reporting rates provides important context and suggests these signals may reflect underlying disease risk rather than drug effects.","specificNumbers":"","methodology":"This pharmacovigilance study analyzed adverse drug reports from the FDA Adverse Events Reporting System (FAERS) from 2005 to 2023. Descriptive and disproportionality analyses were performed using reported odds ratios. An unmasking analysis was conducted to identify individual drug contributions. GLP-1 RAs were compared against metformin and orlistat as reference drugs. Selected preferred terms related to suicidal ideation, self-injury, and suicide were analyzed.","limitations":"FAERS is a spontaneous reporting system with inherent biases including underreporting, reporting bias (more attention to GLP-1 psychiatric effects increases reporting), and the inability to establish causation. Patients taking these drugs often have comorbid conditions (depression, diabetes) that independently increase suicide risk. The comparison with metformin is informative but both populations differ in many ways. Denominator data (total prescriptions) is not available in FAERS, preventing incidence rate calculations."},{"rthcId":"RPEP-08307","title":"MEN1/DAXX/ATRX mutations enhance progression-free survival in gastroenteropancreatic neuroendocrine tumors treated with peptide receptor radionuclide therapy.","authors":"Gujarathi, Rushabh; Abou Azar, Sara; Tobias, Joseph; Polite, Blase N; Setia, Namrata; Feinberg, Nicholas; Appelbaum, Daniel E; Keutgen, Xavier M; Liao, Chih-Yi","year":2024,"journal":"Endocrine-related cancer, 31(11)","doi":"10.1530/ERC-24-0065","pmid":"39093924","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08308","title":"Peptide Receptor Radionuclide Therapy versus Capecitabine/Temozolomide for the Treatment of Metastatic Pancreatic Neuroendocrine Tumors.","authors":"Gujarathi, Rushabh; Tobias, Joseph; Abou Azar, Sara; Keutgen, Xavier M; Liao, Chih-Yi","year":2024,"journal":"Cancers, 16(17)","doi":"10.3390/cancers16172993","pmid":"39272851","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08309","title":"A Comprehensive Review of the Role of GLP-1 Agonists in Weight Management and Their Effect on Metabolic Parameters Such as Blood Glucose, Cholesterol, and Blood Pressure.","authors":"Gul, Ushna; Aung, Thandar; Martin, Mehwish; Farrukh, Daanyal N; Shah, Pari C; Lovely, Zeenia S; Marroquín León, Esaúl; Alansaari, Mohamed; Maini, Shriya; Fariduddin, Muddasir Mohammed; Ullah, Ashraf; Nazir, Zahra","year":2024,"journal":"Cureus, 16(12), e76519","doi":"10.7759/cureus.76519","pmid":"39872560","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08310","title":"Early Conversion of Intensive Insulin Therapy to IDegLira Demonstrates Higher Efficacy and Safety in Reducing Fasting Blood Glucose and HbA1c in T2DM Patients.","authors":"Guo, Caiyun; Lu, Yang","year":2024,"journal":"Diabetes, metabolic syndrome and obesity : targets and therapy, 17, 3217-3226","doi":"10.2147/DMSO.S472174","pmid":"39224113","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08311","title":"Depot-specific differences and heterogeneity of adipose-derived stem cells in diet-induced obesity.","authors":"Guo, Honglin; Sheng, Ailing; Qi, Xiangyu; Zhu, Lin; Wang, Guanyu; Zou, Yizhou; Guan, Qingbo; Lu, Yuntao; Tang, Hui; Hou, Xu","year":2024,"journal":"Obesity (Silver Spring, Md.), 32(12), 2275-2285","doi":"10.1002/oby.24149","pmid":"39496515","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08312","title":"Association between different GLP-1 receptor agonists and acute pancreatitis: case series and real-world pharmacovigilance analysis.","authors":"Guo, Hui; Guo, Qian; Li, Zhiqiang; Wang, Ze","year":2024,"journal":"Frontiers in pharmacology, 15, 1461398","doi":"10.3389/fphar.2024.1461398","pmid":"39605914","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08313","title":"LIRAGLUTIDE ALLEVIATES ACUTE LUNG INJURY AND MORTALITY IN PNEUMONIA-INDUCED SEPSIS THROUGH REGULATING SURFACTANT PROTEIN EXPRESSION AND SECRETION.","authors":"Guo, Junping; Chen, Xinghua; Wang, Cole; Ruan, Feng; Xiong, Yunhe; Wang, Lijun; Abdel-Razek, Osama; Meng, Qinghe; Shahbazov, Rauf; Cooney, Robert N; Wang, Guirong","year":2024,"journal":"Shock (Augusta, Ga.), 61(4), 601-610","doi":"10.1097/SHK.0000000000002285","pmid":"38150354","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08314","title":"Liraglutide alleviates sepsis-induced acute lung injury by regulating pulmonary surfactant through inhibiting autophagy.","authors":"Guo, Junping; Zhang, Xiao; Pan, Ran; Zheng, Yueliang; Chen, Wei; Wang, Lijun","year":2024,"journal":"Immunopharmacology and immunotoxicology, 46(5), 573-582","doi":"10.1080/08923973.2024.2384897","pmid":"39112014","tags":["glp-1","acute-lung-injury","sepsis"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Liraglutide, a GLP-1 receptor agonist, protected mice from sepsis-induced acute lung injury (ALI) by restoring pulmonary surfactant production and inhibiting excessive autophagy. Treated mice survived longer, had less lung inflammation, less pulmonary edema (lower wet/dry weight ratio), and less cell death compared to untreated ALI mice. In cell culture, liraglutide reversed the damage caused by bacterial toxins (LPS) and restored expression of surfactant proteins SP-A and SP-B. The protective effects were blocked by rapamycin (an autophagy activator), confirming that liraglutide works by inhibiting autophagy.","whyItMatters":"Sepsis-induced acute lung injury is a life-threatening condition with limited treatment options and high mortality. This study reveals an unexpected therapeutic role for liraglutide — a drug millions take for diabetes and obesity — in protecting lungs during sepsis. The mechanism through pulmonary surfactant regulation is particularly interesting because surfactant dysfunction is a hallmark of acute respiratory distress syndrome (ARDS).","specificNumbers":"","methodology":"C57BL/6 mice were given an ALI model and then treated with subcutaneous liraglutide at different concentrations. Researchers measured survival rates, lung wet/dry weight ratios, inflammatory markers in bronchoalveolar lavage fluid, lung tissue damage, and cell death. In parallel, MLE-12 lung epithelial cells were stimulated with LPS and treated with liraglutide, measuring cell viability, proliferation, apoptosis, surfactant protein expression (SP-A, SP-B), and autophagy markers. Rapamycin was used to confirm the autophagy-dependent mechanism.","limitations":"This is an animal study in mice with a chemically induced sepsis model, which may differ from the complexity of human sepsis. The cell line used (MLE-12) is a mouse lung epithelial cell line, not primary human cells. The study did not test different timing windows for liraglutide administration, and the optimal dose for lung protection in humans is unknown. The sepsis model may not capture all aspects of clinical ALI/ARDS."},{"rthcId":"RPEP-08315","title":"Novel analgesic peptide derived from Cinobufacini injection suppressing inflammation and pain via ERK1/2/COX-2 pathway.","authors":"Guo, Li; Zhang, Sai; Zhang, Cong; Ren, Shuang; Zhou, Zihan; Wang, Fengyuan; Wang, Yuexuan; Chen, Qiqi; Wang, Yubing; Lee, Wen-Hui; Zhu, Kui; Qin, Di; Gao, Yuanyuan; Sun, Tongyi","year":2024,"journal":"International immunopharmacology, 141, 112918","doi":"10.1016/j.intimp.2024.112918","pmid":"39159558","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The peptide CI5, isolated from Cinobufacini injection, demonstrated significant analgesic and anti-inflammatory effects in multiple mouse models. It relieved pain in the acetic acid writhing test and formalin inflammatory pain model, and prevented carrageenan-induced paw edema.\n\nMechanistically, CI5 reduced levels of key inflammatory markers (IL-6, TNF-α, IL-1β, and PGE2). LC-MS/MS analysis revealed that CI5 exerts its effects by binding to the Rac-2 protein, which sits upstream of the ERK1/2/COX-2 inflammatory signaling axis — the same pathway targeted by common NSAIDs like ibuprofen.","whyItMatters":"Chronic inflammatory pain remains difficult to treat without side effects from existing drugs. Identifying a natural peptide that targets the same COX-2 pathway as NSAIDs but through a different upstream mechanism could lead to new pain treatments with potentially fewer gastrointestinal and cardiovascular side effects.","specificNumbers":"","methodology":"Researchers isolated the CI5 peptide from Cinobufacini injection and tested it in three mouse pain/inflammation models: the acetic acid writhing test, the formalin inflammatory pain model, and carrageenan-induced paw edema. They measured inflammatory cytokine levels and used LC-MS/MS proteomics to identify the molecular target and signaling pathway.","limitations":"All experiments were conducted in mice, and results may not translate to humans. The study did not compare CI5's efficacy to established analgesics like NSAIDs or opioids. Dosing, pharmacokinetics, and potential toxicity in higher organisms were not evaluated. The specific structure and stability of CI5 as a therapeutic candidate need further characterization."},{"rthcId":"RPEP-08316","title":"Effects of Aeromonas infection on the immune system, physical barriers and microflora structure in the intestine of juvenile grass carp (Ctenopharyngodon idella).","authors":"Guo, Meixing; Peng, Ran; Jin, Kelan; Zhang, Xia; Mo, Huilan; Li, Xiang; Qu, Fufa; Tang, Jianzhou; Cao, Shenping; Zhou, Yonghua; He, Zhimin; Mao, Zhuangwen; Fan, Junde; Li, Jianzhong; Liu, Zhen","year":2024,"journal":"Fish & shellfish immunology, 153, 109790","doi":"10.1016/j.fsi.2024.109790","pmid":"39059563","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08317","title":"Molecular nociceptive mechanisms in migraine: The migraine cascade.","authors":"Guo, Song; Christensen, Sarah Louise; Al-Karagholi, Mohammad Al-Mahdi; Olesen, Jes","year":2024,"journal":"European journal of neurology, 31(8), e16333","doi":"10.1111/ene.16333","pmid":"38894592","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08318","title":"VPAC1 and VPAC2 receptors mediate tactile hindpaw hypersensitivity and carotid artery dilatation induced by PACAP38 in a migraine relevant mouse model.","authors":"Guo, Song; Rasmussen, Rikke Holm; Hay-Schmidt, Anders; Ashina, Messoud; Asuni, Ayodeji A; Jensen, Jeppe Møller; Holm, Anja; Lauritzen, Sabrina Prehn; Dorsam, Glenn; Hannibal, Jens; Georg, Birgitte; Kristensen, David Møbjerg; Olesen, Jes; Christensen, Sarah Louise","year":2024,"journal":"The journal of headache and pain, 25(1), 126","doi":"10.1186/s10194-024-01830-2","pmid":"39085771","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08319","title":"Diagnostic and prognostic value of microRNA423-5p in patients with heart failure.","authors":"Guo, Xiaohua; Zhou, Yi; Huang, Honghao; Zong, Zhen; Xin, Mei; Yang, Ke","year":2024,"journal":"Journal of cardiothoracic surgery, 19(1), 550","doi":"10.1186/s13019-024-03091-1","pmid":"39354595","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08320","title":"Dimeric Drug Polymeric Micelles with Acid-Active Tumor Targeting and FRET-indicated Drug Release.","authors":"Guo, Xing; Wang, Lin; Duval, Kayla; Fan, Jing; Zhou, Shaobing; Chen, Zi","year":2024,"journal":"ArXiv","doi":null,"pmid":"39130205","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08321","title":"Semaglutide in Heart Failure: A Systematic Review of Outcomes of Semaglutide in Heart Failure Patients.","authors":"Gupta, Nishtha; Uwawah, Tesingin D; Singh, Kamaldeep; Madan, Hritik; Kumar, Siddharth; Midha, Bharat; Soni, Kriti; Singh, Aparjit; Bhogal, Amandeep; Jain, Arpit","year":2024,"journal":"Cureus, 16(7), e64668","doi":"10.7759/cureus.64668","pmid":"39149678","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Four studies (3 RCTs + 1 observational study) examining semaglutide in heart failure patients found statistically significant improvements in:\n\n- Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score (P<0.001) — measuring quality of life and symptom burden\n- Body weight reduction (P<0.001)\n- Six-minute walk distance (P<0.001) — measuring exercise capacity\n- C-reactive protein (CRP) levels (P<0.001) — measuring systemic inflammation\n- Major adverse cardiac events: HR = 0.76 (95% CI: 0.62–0.92) — a 24% risk reduction\n\nAdverse effects were observed but were not significantly worse than placebo.","whyItMatters":"Heart failure affects approximately 64 million people worldwide and remains a leading cause of hospitalization and death. Current treatments improve survival but many patients continue to have debilitating symptoms and poor quality of life. Semaglutide's ability to simultaneously improve symptoms (KCCQ scores), functional capacity (walking distance), inflammation (CRP), and hard outcomes (MACE) makes it potentially transformative — addressing multiple aspects of heart failure that existing treatments may not fully cover.","specificNumbers":"","methodology":"A systematic review was performed searching PubMed/Medline, the Cochrane Library, and Google Scholar through May 10, 2024. Studies meeting inclusion criteria were selected, yielding four eligible studies: three randomized controlled trials and one observational study. Qualitative analysis synthesized findings across studies for quality of life, body weight, exercise capacity, inflammation, cardiovascular events, and adverse effects.","limitations":"Only four studies were included, limiting the breadth of evidence. The mix of RCTs and observational studies introduces heterogeneity. A qualitative rather than quantitative meta-analysis was performed, so pooled effect sizes may not be available. The specific heart failure subtypes (HFpEF vs HFrEF), semaglutide doses, and treatment durations across the four studies are not detailed in the abstract. Publication in Cureus suggests a lower-impact venue for the systematic review itself, though the included trials were published in high-impact journals. Long-term safety of semaglutide in heart failure beyond the trial periods is unknown."},{"rthcId":"RPEP-08322","title":"Effect of Photoperiod and Illuminance on Daily Activity Patterns, Physiology, and NPY Peptide Expression in Migratory Redheaded Buntings (Emberiza bruniceps).","authors":"Gupta, Preeti; Sur, Sayantan; Naseem, Asma; Malik, Shalie","year":2024,"journal":"Neuroendocrinology, 114(11), 993-1004","doi":"10.1159/000540394","pmid":"39053433","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08323","title":"Exploring the protective effects of vasoactive intestinal peptides on dry eye disease in SARS-CoV-2 survivors.","authors":"Gushansky, Konstantin Y; Tuuminen, Raimo","year":2024,"journal":"Molecular vision, 30, 489-496","doi":null,"pmid":"39959180","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 1,165 SARS-CoV-2 hospitalized patients without pre-existing dry eye:\n\n- 167 patients (14.3%) developed dry eye disease within 6 months of discharge\n- Metoclopramide: strongest association, OR 13.413 (p<0.001), >50% incidence in affected patients\n- Laxatives: lactulose OR 1.939 (p=0.016), polyethylene glycol OR 2.094 (p=0.015)\n- Omeprazole: protective, OR 0.332 (p<0.001) — 67% risk reduction\n- Polypharmacy increased dry eye odds: OR 1.629 (p=0.015)\n- Age, gender, and vaccination status were not significant\n\nVasoactive intestinal peptide (VIP) is proposed as the pathophysiological link between gut and lacrimal gland function, connecting GI medication effects to dry eye outcomes.","whyItMatters":"Dry eye disease affects hundreds of millions of people worldwide and is particularly common after COVID-19. Understanding that gut medications can significantly influence dry eye risk — and that VIP may be the connecting mechanism — opens new avenues for prevention and treatment. If VIP-based therapies can protect the tear glands, it could benefit both COVID survivors and the broader dry eye population.","specificNumbers":"","methodology":"Retrospective cohort study using electronic medical records from patients hospitalized for SARS-CoV-2 between April 2020 and December 2023. Patients were aged 18+ without pre-existing dry eye. Exclusions: ICU admissions, malignancies, recent ocular interventions, chronic dry-eye-inducing medications. Logistic regression adjusted for age, gender, and vaccination status evaluated associations between GI medications and dry eye development within 6 months post-discharge.","limitations":"This is a retrospective observational study and cannot establish causation between GI medications and dry eye. The VIP mechanism is proposed but not directly measured — no VIP levels were assessed. Confounding factors beyond age, gender, and vaccination may exist. The very high odds ratio for metoclopramide (13.4) may be influenced by confounding with disease severity. The study was limited to hospitalized patients, who may not represent all COVID-19 cases. Dry eye diagnosis methods are not detailed."},{"rthcId":"RPEP-08324","title":"Dual and Triple Incretin-Based Co-agonists: Novel Therapeutics for Obesity and Diabetes.","authors":"Gutgesell, Robert M; Nogueiras, Rubén; Tschöp, Matthias H; Müller, Timo D","year":2024,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 15(5), 1069-1084","doi":"10.1007/s13300-024-01566-x","pmid":"38573467","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08325","title":"Super response to liraglutide in people with obesity: A case report and literature review.","authors":"Gutiérrez Medina, Sonsoles; Sánchez Campayo, Elena; Guadalix, Sonsoles; Escalada, Javier","year":2024,"journal":"Endocrinologia, diabetes y nutricion, 71(10), 447-453","doi":"10.1016/j.endien.2024.11.012","pmid":"39617632","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08326","title":"Clinical outcomes of patients with heart failure and atrial fibrillation: Experience from an outpatient heart failure clinic in Colombia.","authors":"Gómez, José Alejandro; Valencia, Santiago; Franco, Isabela; Cardona, Pablo; Vanegas, Johanna Marcela; Gómez, Camilo Andrés; Díaz, James Samir","year":2024,"journal":"Current problems in cardiology, 49(12), 102841","doi":"10.1016/j.cpcardiol.2024.102841","pmid":"39242064","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08327","title":"Supplementation with ions enhances the efficiency of nucleic acid delivery with cell-penetrating peptides.","authors":"Gümüşoğlu, İrem Ilgın; Maloverjan, Maria; Porosk, Ly; Pooga, Margus","year":2024,"journal":"Biochimica et biophysica acta. General subjects, 1868(12), 130719","doi":"10.1016/j.bbagen.2024.130719","pmid":"39369860","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08328","title":"A novel LL-37@NH2@Fe3O4 inhibits the proliferation of the leukemia K562 cells: in-vitro study.","authors":"Habibi, Alireza; Davari, Aynaz; Isazadeh, Khosro","year":2024,"journal":"Scientific reports, 14(1), 22245","doi":"10.1038/s41598-024-71946-7","pmid":"39333586","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08329","title":"Decoding the molecular and structural determinants of the neurokinin A and Aβ1-42 peptide cross-interaction in the amyloid cascade pathway.","authors":"Habibnia, Mohsen; Catalina-Hernandez, Eric; Lopez-Martin, Mario; Masnou-Sanchez, David; Peralvarez-Marin, Alex","year":2024,"journal":"iScience, 27(11), 111187","doi":"10.1016/j.isci.2024.111187","pmid":"39559760","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Neurokinin A (NKA), a tachykinin neuropeptide, directly interacts with Alzheimer's Aβ1-42 peptide and modulates its amyloid aggregation cascade. A phenylalanine residue in NKA's FXGLM signature motif was critical for this interaction (demonstrated by Phe-to-Trp substitution). Cellular experiments showed that the NKA-Aβ interaction decreased Aβ peptide toxicity, suggesting NKA may have a protective role against amyloid-driven cell damage.","whyItMatters":"Alzheimer's disease is driven partly by the aggregation of Aβ peptide into toxic amyloid plaques. This study reveals that a brain neuropeptide (NKA) — already known for its role in pain, gut motility, and the brain-gut axis — physically interacts with Aβ and reduces its toxicity. This opens a new angle on Alzheimer's research: the balance of endogenous neuropeptides in the brain may influence amyloid aggregation, and NKA could be a natural protective factor.","specificNumbers":"NKA-Aβ1-42 interaction confirmed · FXGLM motif Phe residue = critical for interaction · Reduced Aβ toxicity in cell experiments · Computational + experimental biophysics approach","methodology":"Combined computational and experimental biophysics approach. In silico modeling predicted NKA-Aβ interactions. Phe-to-Trp substitution in NKA's FXGLM motif tested the importance of specific residues. In vitro experiments assessed peptide-peptide interaction and effects on amyloid aggregation. Cellular experiments measured Aβ toxicity with and without NKA.","limitations":"This is an in vitro and computational study — the NKA-Aβ interaction has not been demonstrated in living brain tissue or animal models of Alzheimer's. The physiological concentrations of NKA and Aβ in the brain may differ from experimental conditions. Whether NKA actually reaches Aβ deposits in the Alzheimer's brain and modulates aggregation in vivo is unknown."},{"rthcId":"RPEP-08330","title":"Impact of Manufacturing Process and Compounding on Properties and Quality of Follow-On GLP-1 Polypeptide Drugs.","authors":"Hach, Morten; Engelund, Dorthe Kot; Mysling, Simon; Mogensen, Jesper Emil; Schelde, Ole; Haselmann, Kim F; Lamberth, Kasper; Vilhelmsen, Thomas Kvistgaard; Malmstrøm, Joan; Højlys-Larsen, Kim Bonde; Rasmussen, Tina Secher; Borch-Jensen, Jonas; Mortensen, Rasmus Worm; Jensen, Thomas Marker Thams; Kesting, Julie Regitze; Catarig, Andrei-Mircea; Asgreen, Désirée J; Christensen, Leif; Staby, Arne","year":2024,"journal":"Pharmaceutical research, 41(10), 1991-2014","doi":"10.1007/s11095-024-03771-6","pmid":"39379664","tags":["glp-1-agonists","drug-quality"],"studyType":"laboratory-analysis","evidenceStrength":"moderate","keyFinding":"Extensive laboratory testing of 26 follow-on (generic/compounded) GLP-1 products — 16 injectable semaglutide, 8 oral semaglutide, and 2 injectable liraglutide — revealed significant quality concerns compared to brand-name originator products.\n\nKey problems found: follow-on injectable semaglutide products contained new impurities including high molecular weight proteins, trace metals, anions, counterions, and residual solvents. Several oral semaglutide follow-ons had markedly less semaglutide than their labels claimed and showed different drug release profiles that could reduce how much drug actually gets absorbed. Some follow-on products contained neoepitopes — protein fragments not found in originators — that could trigger unwanted immune reactions. Liraglutide follow-ons showed increased tendency to form fibrils (protein aggregates), indicating reduced physical stability.","whyItMatters":"With GLP-1 drugs in massive demand, follow-on and compounded versions are flooding the market worldwide. This study provides hard analytical data showing that many of these products are not equivalent to brand-name Ozempic, Wegovy, Rybelsus, or Saxenda. The differences aren't theoretical — less drug than labeled, new impurities, and potential immune-triggering proteins are concrete safety and efficacy concerns. This is especially relevant as patients and providers navigate supply shortages and cost pressures.","specificNumbers":"26 follow-on products tested · 16 injectable semaglutide · 8 oral semaglutide · 2 injectable liraglutide · New impurities found including HMW proteins, trace metals, residual solvents · Oral products had less semaglutide than label claim · Neoepitopes indicating immunogenicity risk","methodology":"Researchers compared commercially available follow-on GLP-1 products against originator products using multiple analytical techniques: various chromatography methods with UV and mass spectrometry detection, inductively coupled plasma optical emission spectroscopy and mass spectrometry (for metals), nuclear magnetic resonance, dissolution testing, computational immunogenicity prediction (peptide/MHC II binding), and fibrillation assays for physical stability.","limitations":"This study was conducted by Novo Nordisk, the manufacturer of originator semaglutide (Ozempic/Wegovy) and liraglutide (Saxenda/Victoza), creating a potential conflict of interest. The analysis was laboratory-based only — the actual clinical impact of the identified differences on patient outcomes is unknown. The specific follow-on products tested were not named. Not all follow-on products on the market were tested."},{"rthcId":"RPEP-08331","title":"Impact of Glucagon-Like Peptide 1 Receptor Agonists on Biochemical Markers of the Initiation of Atherosclerotic Process.","authors":"Hachuła, Marcin; Kosowski, Michał; Ryl, Sabina; Basiak, Marcin; Okopień, Bogusław","year":2024,"journal":"International journal of molecular sciences, 25(3)","doi":"10.3390/ijms25031854","pmid":"38339133","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08332","title":"Influence of Dulaglutide on Serum Biomarkers of Atherosclerotic Plaque Instability: An Interventional Analysis of Cytokine Profiles in Diabetic Subjects-A Pilot Study.","authors":"Hachuła, Marcin; Kosowski, Michał; Basiak, Marcin; Okopień, Bogusław","year":2024,"journal":"Medicina (Kaunas, Lithuania), 60(6)","doi":"10.3390/medicina60060908","pmid":"38929525","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Dulaglutide treatment produced significant reductions in two key biomarkers of atherosclerotic plaque instability: pentraxin 3 (PTX3) and matrix metalloproteinase-9 (MMP-9). Both markers are associated with plaque vulnerability — the likelihood that a fatty deposit in an artery will rupture and cause a heart attack or stroke.\n\nThe study also documented significant improvements in anthropometric measurements, blood pressure, fasting glucose, and HbA1c levels (median baseline 8.8%), demonstrating that dulaglutide's cardiovascular benefits may operate through multiple pathways simultaneously.","whyItMatters":"Heart attacks and strokes caused by unstable arterial plaques account for over half of all diabetes-related deaths. If GLP-1 receptor agonists like dulaglutide can stabilize these plaques — not just improve blood sugar — it would represent a major additional benefit of these increasingly popular diabetes drugs and could change how clinicians prioritize them for high-risk cardiovascular patients.","specificNumbers":"","methodology":"This was an interventional pilot study involving 34 participants aged 41-81 years (average age 61) with type 2 diabetes, dyslipidemia, and atherosclerosis confirmed by B-mode ultrasonography. All participants were started on dulaglutide treatment, and researchers measured levels of four atherosclerosis-related biomarkers — PTX3, copeptin, MMP-9, and lipoprotein(a) — before and after treatment.","limitations":"This was a small pilot study with only 34 participants and no control group receiving placebo, making it impossible to rule out that the biomarker improvements were simply due to better blood sugar control or other lifestyle changes. The abstract does not specify the treatment duration or provide exact p-values for all comparisons. Larger randomized controlled trials are needed to confirm these findings."},{"rthcId":"RPEP-08333","title":"Investigating the Preventive Effects of Oral Consumption of Dactylorhiza Maculate (Salep) Hydro-alcoholic Extract on Appetite and Body Weight in Male Rats.","authors":"Haghshenas, H; Molayem, M; Shafiei Jahromi, N; Kargar Jahromi, H; Dehghani, M; Ebrahimi, B; Moazeni, R; Rezaeian, S; Shaterian, N; Daniali, S","year":2024,"journal":"Archives of Razi Institute, 79(2), 418-425","doi":"10.32592/ARI.2024.79.2.418","pmid":"39463707","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Salep extract at 160 and 320 mg/kg caused significant weight loss in rats over 29 days. The extract shifted the balance of appetite-regulating peptides in favor of satiety:\n\nIncreased: leptin, adiponectin, AgRP, obestatin, CCK, chemerin, and total antioxidants.\nDecreased: ghrelin, omentin, resistin, NPY, amylin, orexin-A, epinephrine, and MDA (oxidative stress marker).\n\nLipid profiles also improved. The simultaneous reduction of multiple appetite-stimulating peptides (ghrelin, NPY, orexin-A) combined with elevation of satiety signals (CCK, obestatin, leptin) suggests a broad anti-obesity mechanism affecting both central and peripheral appetite regulation.","whyItMatters":"The obesity epidemic affects hundreds of millions of people, and current drug options are limited, expensive, or have significant side effects. Understanding how natural compounds affect the body's intricate network of appetite-regulating peptides could lead to new anti-obesity approaches. The breadth of peptide changes observed — affecting ghrelin, NPY, CCK, and many others simultaneously — is unusual and suggests a multi-target mechanism that could be more effective than single-target drugs.","specificNumbers":"","methodology":"Forty male Wistar rats were divided into five groups: control, sham, and three Salep extract dose groups (80, 160, and 320 mg/kg). The hydro-alcoholic extract was administered by oral gavage daily for 29 days. On day 29, blood and tissue samples were collected. ELISA kits measured 12 appetite and metabolic hormones/peptides (adiponectin, obestatin, resistin, orexin-A, insulin, epinephrine, AgRP, omentin, chemerin, amylin, NPY, ghrelin) plus leptin, CCK, antioxidants, and lipid profile factors.","limitations":"This is an animal study in healthy male rats, not obese rats or humans. The 29-day treatment period is relatively short. The mechanism by which Salep extract simultaneously modifies over a dozen different peptide hormones is unclear and may reflect indirect metabolic effects rather than specific peptide-targeting activity. The AgRP increase is paradoxical (AgRP normally stimulates appetite) and is not explained. No dose-response analysis for individual peptides is described. Human bioavailability and safety of Salep extract are unknown."},{"rthcId":"RPEP-08334","title":"Glucagon-like peptide-1 (GLP-1) receptor agonists for headache and pain disorders: a systematic review.","authors":"Halloum, Wael; Dughem, Yousef Al; Beier, Dagmar; Pellesi, Lanfranco","year":2024,"journal":"The journal of headache and pain, 25(1), 112","doi":"10.1186/s10194-024-01821-3","pmid":"38997662","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08335","title":"Effects of Semaglutide in Doxorubicin-Induced Cardiac Toxicity in Wistar Albino Rats.","authors":"HamaSalih, Raz Muhammed","year":2024,"journal":"Cancer management and research, 16, 731-740","doi":"10.2147/CMAR.S468453","pmid":"38952352","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08336","title":"Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists: Exploring Their Impact on Diabetes, Obesity, and Cardiovascular Health Through a Comprehensive Literature Review.","authors":"Hamed, Khalid; Alosaimi, Mohammed N; Ali, Bashaer A; Alghamdi, Atheer; Alkhashi, Taif; Alkhaldi, Salman S; Altowarqi, Nawaf A; Alzahrani, Hayat; Alshehri, Abdullah M; Alkhaldi, Rami K; Alqahtani, Khalid W; Alharbi, Nehal H; Alhulayfi, Hanan F; Sharifi, Shuruq Y; Dighriri, Ibrahim M","year":2024,"journal":"Cureus, 16(9), e68390","doi":"10.7759/cureus.68390","pmid":"39355484","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Head-to-head clinical studies showed that GLP-1 receptor agonists outperform conventional antidiabetic medicines in both glycemic management and weight reduction. Cardiovascular outcome studies found that several drugs in this class reduce the frequency of major adverse cardiovascular events.\n\nThe medications also show promise for non-alcoholic fatty liver disease (NAFLD). However, the high cost of these drugs creates significant barriers to access and equitable healthcare. Current research is focused on expanding therapeutic applications and developing oral formulations with greater potency and bioavailability.","whyItMatters":"Type 2 diabetes and obesity are among the world's most pressing health challenges, often occurring together and driving cardiovascular disease. GLP-1 receptor agonists represent a paradigm shift because they address multiple conditions simultaneously — blood sugar, weight, and heart risk — rather than treating each in isolation. This review consolidates the evidence at a time when these drugs are seeing explosive demand.","specificNumbers":"","methodology":"The authors conducted a comprehensive literature review by searching PubMed, EMBASE, and Cochrane Library databases. They examined studies covering the mechanisms of action, clinical effectiveness, safety profiles, and socioeconomic implications of GLP-1 receptor agonists across diabetes, obesity, cardiovascular disease, and fatty liver disease.","limitations":"As a literature review rather than a meta-analysis or original study, this paper synthesizes existing evidence without conducting new statistical analyses. The specific studies included and their individual quality are not detailed in the abstract. The review acknowledges that effectiveness, safety, and dosing vary between different GLP-1 receptor agonists, but the abstract does not provide drug-by-drug comparisons. Long-term data beyond the timeframes of existing cardiovascular outcome trials remain limited."},{"rthcId":"RPEP-08337","title":"Chronic GLP1 therapy reduces postprandial IL6 in obese humans with prediabetes.","authors":"Hamidi, Vala; Wang, Hongyu; Pham, Vi; Bermudez Saint Andre, Karla; Taegtmeyer, Heinrich; Gutierrez, Absalon D","year":2024,"journal":"Cardiovascular endocrinology & metabolism, 13(1), e0298","doi":"10.1097/XCE.0000000000000298","pmid":"38187405","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08338","title":"Glucose-dependent insulinotropic polypeptide receptor signaling alleviates gut inflammation in mice.","authors":"Hammoud, Rola; Kaur, Kiran Deep; Koehler, Jacqueline A; Baggio, Laurie L; Wong, Chi Kin; Advani, Katie E; Yusta, Bernardo; Efimova, Irina; Gribble, Fiona M; Reimann, Frank; Fishman, Sigal; Varol, Chen; Drucker, Daniel J","year":2024,"journal":"JCI insight, 10(3)","doi":"10.1172/jci.insight.174825","pmid":"39723966","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08339","title":"Diversification of Phage-Displayed Peptide Libraries with Noncanonical Amino Acid Mutagenesis and Chemical Modification.","authors":"Hampton, J Trae; Liu, Wenshe Ray","year":2024,"journal":"Chemical reviews, 124(9), 6051-6077","doi":"10.1021/acs.chemrev.4c00004","pmid":"38686960","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08340","title":"The influence of intraoral cryotherapy on postoperative pain and substance P in symptomatic apical periodontitis: randomized clinical study.","authors":"Hamza, Esraa Mohammed; Abd El Aziz, Tarek Mustafa; Obeid, Maram Farouk","year":2024,"journal":"Scientific reports, 14(1), 13890","doi":"10.1038/s41598-024-64071-y","pmid":"38880787","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08341","title":"Safety and Effectiveness of Dulaglutide in the Treatment of Type 2 Diabetes Mellitus: A Korean Real-World Post-Marketing Study.","authors":"Han, Jeonghee; Lee, Woo Je; Hur, Kyu Yeon; Cho, Jae Hyoung; Lee, Byung Wan; Park, Cheol-Young","year":2024,"journal":"Diabetes & metabolism journal, 48(3), 418-428","doi":"10.4093/dmj.2023.0030","pmid":"38310883","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08342","title":"Efficacy and Safety of Ivabradine for Patients With Acute Heart Failure: Meta-Analysis of Randomized Controlled Trials.","authors":"Han, Jing; Wang, Qi; Jiang, Lantian; Yin, Xia","year":2024,"journal":"Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc, 29(6), e70012","doi":"10.1111/anec.70012","pmid":"39425897","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08343","title":"Fulminant myocarditis associated with human rhinovirus A66 infection: a case report.","authors":"Han, Shuaibing; Liu, Jing; Feng, Ziheng; Mao, Yiyang; Gao, Hengmiao; Xie, Zhengde; Qian, Suyun; Xu, Lili","year":2024,"journal":"Frontiers in pediatrics, 12, 1480724","doi":"10.3389/fped.2024.1480724","pmid":"39529970","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08344","title":"Once-weekly semaglutide versus placebo in adults with increased fracture risk: a randomised, double-blinded, two-centre, phase 2 trial.","authors":"Hansen, Morten S; Wölfel, Eva M; Jeromdesella, Shakespeare; Møller, Jens-Jakob K; Ejersted, Charlotte; Jørgensen, Niklas R; Eastell, Richard; Hansen, Stinus G; Frost, Morten","year":2024,"journal":"EClinicalMedicine, 72, 102624","doi":"10.1016/j.eclinm.2024.102624","pmid":"38737002","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08345","title":"Recent advances in therapeutic strategies for Alzheimer's and Parkinson's disease using protein/peptide co-modified polymer nanoparticles.","authors":"Hanumanthappa, Ramesha; Parthasarathy, Aravind; Heggannavar, Geetha B; Pc, Kiran; Nanjaiah, Hemalatha; Kumbhar, Ramhari; Devaraju, Kuramkote Shivanna","year":2024,"journal":"Neuroprotection (Chichester, England), 2(4), 255-275","doi":"10.1002/nep3.60","pmid":"41383377","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08346","title":"Development and Clinical Applications of Therapeutic Cancer Vaccines with Individualized and Shared Neoantigens.","authors":"Hao, Qing; Long, Yuhang; Yang, Yi; Deng, Yiqi; Ding, Zhenyu; Yang, Li; Shu, Yang; Xu, Heng","year":2024,"journal":"Vaccines, 12(7)","doi":"10.3390/vaccines12070717","pmid":"39066355","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08347","title":"A parathyroid hormone related supramolecular peptide for multi-functionalized osteoregeneration.","authors":"Hao, Zhuowen; Feng, Qinyu; Wang, Yi; Wang, Ying; Li, Hanke; Hu, Yingkun; Chen, Tianhong; Wang, Junwu; Chen, Renxin; Lv, Xuan; Yang, Zhiqiang; Chen, Jiayao; Guo, Xiaodong; Li, Jingfeng","year":2024,"journal":"Bioactive materials, 34, 181-203","doi":"10.1016/j.bioactmat.2023.12.014","pmid":"38235308","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08348","title":"Putting More Weight on Obesity Trials in Heart Failure.","authors":"Harrington, Josephine; Sattar, Naveed; Felker, G Michael; Januzzi, James L; Lam, Carolyn S P; Pagidipati, Neha J; Pandey, Ambarish; Van Spall, Harriette G C; McGuire, Darren K","year":2024,"journal":"Current heart failure reports, 21(3), 194-202","doi":"10.1007/s11897-024-00655-z","pmid":"38619690","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08349","title":"Worth Their Weight? An Update on New and Emerging Pharmacologic Agents for Obesity and Their Potential Role for Persons with Cardiac Conditions.","authors":"Harrington, Josephine; Felker, G Michael; Januzzi, James L; Lam, Carolyn S P; Lingvay, Ildiko; Pagidipati, Neha J; Sattar, Naveed; Van Spall, Harriette G C; Verma, Subodh; McGuire, Darren K","year":2024,"journal":"Current cardiology reports, 26(3), 61-71","doi":"10.1007/s11886-023-02016-z","pmid":"38551786","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08350","title":"Layer 1 NDNF interneurons are specialized top-down master regulators of cortical circuits.","authors":"Hartung, Jan; Schroeder, Anna; Péréz Vázquez, Rodrigo Alejandro; Poorthuis, Rogier B; Letzkus, Johannes J","year":2024,"journal":"Cell reports, 43(5), 114212","doi":"10.1016/j.celrep.2024.114212","pmid":"38743567","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08351","title":"A Systematic Review and Meta-Analysis of an Angiotensin Receptor-Neprilysin Inhibitor in Patients Using a Durable Left Ventricular Assist Device.","authors":"Hasabo, Elfatih A; Isik, Burce; Elgadi, Ammar; Yacoub, Magdi S; Bakr, Mohamed S; Eljack, Mohammed Mahmmoud Fadelallah; Sultan, Sherif; Caliskan, Kadir; Soliman, Osama","year":2024,"journal":"Journal of clinical medicine, 13(24)","doi":"10.3390/jcm13247789","pmid":"39768713","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08352","title":"A Systematic Review and Meta-Analysis of the Efficacy and Safety of Sodium-Glucose Cotransporter-2 Inhibitor in Patients Using Left Ventricular Assist Devices.","authors":"Hasabo, Elfatih A; Isik, Burce; Elgadi, Ammar; Eljack, Mohammed Mahmmoud Fadelallah; Yacoub, Magdi S; Elzomor, Hesham; Sultan, Sherif; Caliskan, Kadir; Soliman, Osama","year":2024,"journal":"Journal of clinical medicine, 13(23)","doi":"10.3390/jcm13237418","pmid":"39685874","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08353","title":"Calcitonin gene-related peptide and intermedin induce phosphorylation of p44/42 MAPK in primary human lymphatic endothelial cells in vitro.","authors":"Hasan, Shirin R; Manolis, Dimitrios; Stephenson, Ewan; Ryskiewicz-Sokalska, Oktawia A; Maraveyas, Anthony; Nikitenko, Leonid L","year":2024,"journal":"Cellular signalling, 121, 111261","doi":"10.1016/j.cellsig.2024.111261","pmid":"38878805","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08354","title":"Therapeutic peptide development revolutionized: Harnessing the power of artificial intelligence for drug discovery.","authors":"Hashemi, Samaneh; Vosough, Parisa; Taghizadeh, Saeed; Savardashtaki, Amir","year":2024,"journal":"Heliyon, 10(22), e40265","doi":"10.1016/j.heliyon.2024.e40265","pmid":"39605829","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08355","title":"Effects of Transcranial Direct Current Stimulation on Clinical Outcomes, Calcitonin Gene-Related Peptide, and Pituitary Adenylate Cyclase-Activating Polypeptide-38 Levels in Menstrual Migraine.","authors":"Hasırcı Bayır, Buse Rahime; Aksu, Serkan; Gezegen, Haşim; Karaaslan, Zerrin; Yüceer, Hande; Cerrahoğlu Şirin, Tuba; Küçükali, Cem İsmail; Kurt, Adnan; Karamürsel, Sacit; Yılmaz, Vuslat; Baykan, Betül","year":2024,"journal":"Neuromodulation : journal of the International Neuromodulation Society, 27(5), 835-846","doi":"10.1016/j.neurom.2024.01.005","pmid":"38506767","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08356","title":"Pharmacovigilance study of GLP-1 receptor agonists for metabolic and nutritional adverse events.","authors":"He, Long; Li, Qiuyu; Yang, Yongfeng; Li, Jiahao; Luo, Wei; Huang, Yilan; Zhong, Xiaoyan","year":2024,"journal":"Frontiers in pharmacology, 15, 1416985","doi":"10.3389/fphar.2024.1416985","pmid":"39040467","tags":["glp-1-agonists"],"studyType":"Pharmacovigilance / Database Analysis","evidenceStrength":"moderate","keyFinding":"Mining the FDA's adverse event database (FAERS) revealed that semaglutide, liraglutide, and exenatide have the highest rates of metabolic and nutritional adverse events among GLP-1 drugs. Semaglutide had the strongest signal (ROR 3.34), followed by liraglutide (ROR 2.78) and exenatide (ROR 2.15).\n\nDehydration emerged as the most common serious metabolic side effect across multiple GLP-1 drugs: it accounted for 25.1% of serious metabolic adverse events for semaglutide, 32.9% for tirzepatide, 23.9% for liraglutide, and 20.9% for dulaglutide. Dulaglutide had the most total adverse event signal types (22), followed by semaglutide (20) and liraglutide (16).","whyItMatters":"With tens of millions of people now taking GLP-1 drugs, understanding their real-world side effect patterns is critical. This study highlights dehydration as a particularly important — and potentially underrecognized — risk across all major GLP-1 drugs. Dehydration can lead to kidney injury, electrolyte imbalances, and hospitalization, especially in elderly patients or those on diuretics.","specificNumbers":"22,404+ total reports analyzed · semaglutide ROR 3.34 · liraglutide ROR 2.78 · exenatide ROR 2.15 · dehydration: 25-33% of serious metabolic AEs across drugs · 7 GLP-1 RAs compared","methodology":"Pharmacovigilance analysis using the FDA Adverse Event Reporting System (FAERS) database. Researchers extracted all metabolic and nutritional adverse event reports for seven GLP-1 receptor agonists from their respective launch dates through Q2 2023. Four statistical methods were used to identify safety signals: reported odds ratio (ROR), proportional reporting ratio (PRR), Empirical Bayesian Geometric Mean, and Bayesian Confidence Propagation Neural Network. Time-to-onset analysis was also performed.","limitations":"FAERS is a voluntary reporting system with inherent biases — popular drugs get more reports, and reporting rates vary over time. The data can't establish causation, only associations. Media attention on semaglutide and tirzepatide may inflate their report counts. No adjustment for patient demographics, comorbidities, or concomitant medications. Under-reporting is a known limitation of all pharmacovigilance databases."},{"rthcId":"RPEP-08357","title":"Preparation and characterization of BSA-loaded liraglutide and platelet fragment nanoparticle delivery system for the treatment of diabetic atherosclerosis.","authors":"He, Mingping; Fang, Ming; Fan, Limin; Maimaitijiang, Alimujiang","year":2024,"journal":"Journal of nanobiotechnology, 22(1), 506","doi":"10.1186/s12951-024-02775-z","pmid":"39180102","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The BSA@LIR-PMF nanoparticles achieved a drug loading rate of 7.96% and encapsulation efficiency of 85.56%, with approximately 77% cumulative drug release over 24 hours. The nanoparticles were spherical, uniform in size, and maintained stable platelet membrane protein structure.\n\nIn functional testing, the nanoparticles effectively inhibited abnormal cell proliferation and migration triggered by oxidized LDL (ox-LDL), reduced reactive oxygen species (ROS) levels and lactate concentrations, and enhanced ATP levels by improving oxidative phosphorylation. In animal models, BSA@LIR-PMF significantly inhibited diabetes-induced atherosclerosis and reduced lipid deposition in the aortas.","whyItMatters":"Liraglutide requires daily injections, which can be burdensome for patients managing chronic conditions. A targeted nanoparticle delivery system could improve drug efficacy while reducing injection frequency. The platelet membrane coating is particularly clever because platelets naturally home to sites of vascular injury — potentially delivering liraglutide directly where atherosclerotic damage is occurring.","specificNumbers":"","methodology":"Researchers prepared nanoparticles by encapsulating liraglutide in bovine serum albumin (BSA) and coating them with platelet membrane fragments (PMF). They characterized the nanoparticles for size, shape, stability, and membrane protein integrity. Effectiveness was tested both in vitro (using ox-LDL-stimulated cells to model atherosclerosis) and in vivo (using diabetic mouse models), measuring cell proliferation, migration, phagocytosis, ROS, metabolic markers, and aortic lipid deposition.","limitations":"This is a preclinical study using cell cultures and animal models — results may not directly translate to humans. The study used bovine serum albumin as the carrier protein, which would need to be replaced with human albumin for clinical use. Long-term safety of repeated nanoparticle administration and potential immune responses to platelet membrane fragments were not assessed. The diabetic atherosclerosis animal model may not fully capture the complexity of human disease."},{"rthcId":"RPEP-08358","title":"Semaglutide ameliorates pressure overload-induced cardiac hypertrophy by improving cardiac mitophagy to suppress the activation of NLRP3 inflammasome.","authors":"He, Wenxiu; Wei, Jiahe; Liu, Xing; Zhang, Zhongyin; Huang, Rongjie; Jiang, Zhiyuan","year":2024,"journal":"Scientific reports, 14(1), 11824","doi":"10.1038/s41598-024-62465-6","pmid":"38782946","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08359","title":"Early onset stage III diabetic nephropathy in a child with Prader-Willi syndrome treated with dulaglutide: a case report.","authors":"He, Yonghua; Xu, Rongrong; Ma, Xueqing; Zhou, Jianhua; Qiu, Liru","year":2024,"journal":"Translational pediatrics, 13(5), 833-839","doi":"10.21037/tp-23-518","pmid":"38840685","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08360","title":"Substance P in the medial amygdala regulates aggressive behaviors in male mice.","authors":"He, Zi-Xuan; Yue, Mei-Hui; Liu, Kai-Jie; Wang, Yao; Qiao, Jiu-Ye; Lv, Xin-Yue; Xi, Ke; Zhang, Ya-Xin; Fan, Jia-Ni; Yu, Hua-Li; He, Xiao-Xiao; Zhu, Xiao-Juan","year":2024,"journal":"Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 49(11), 1689-1699","doi":"10.1038/s41386-024-01863-w","pmid":"38649427","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08361","title":"Glucagon-Like Peptide Receptor-1 Agonists Used for Medically-Supervised Weight Loss in Patients With Hip and Knee Osteoarthritis: Critical Considerations for the Arthroplasty Surgeon.","authors":"Heckmann, Nathanael D; Palmer, Ryan; Mayfield, Cory K; Gucev, Gligor; Lieberman, Jay R; Hong, Kurt","year":2024,"journal":"Arthroplasty today, 27, 101327","doi":"10.1016/j.artd.2024.101327","pmid":"39071832","tags":["GLP-1-agonists","obesity"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"GLP-1 receptor agonists have emerged as an effective weight loss option for morbidly obese patients with hip or knee osteoarthritis who need joint replacement surgery. These patients typically present earlier in life, have more severe symptoms, and experience worse surgical outcomes after total hip or knee arthroplasty.\n\nBeyond weight loss, GLP-1 agonists may have anti-inflammatory and disease-modifying effects on osteoarthritis itself. The review covers single GLP-1 agonists, dual GLP-1/GIP agonists, and triple GLP-1/GIP/glucagon agonists in development.\n\nHowever, a critical perioperative concern is GLP-1-related delayed gastric emptying, which affects anesthesia timing for elective joint replacement surgery. Surgeons must account for this when planning procedures in patients taking these medications.","whyItMatters":"As GLP-1 drugs become the dominant weight loss treatment, orthopedic surgeons will increasingly encounter patients on these medications before joint replacement. This review fills an important gap by addressing both the potential benefits — weight loss and anti-inflammatory effects that could improve surgical outcomes — and the practical safety concern of delayed gastric emptying that could complicate anesthesia.","specificNumbers":"","methodology":"Narrative review examining the current landscape of GLP-1 receptor agonists and related multi-agonist drugs, their effects on obesity and osteoarthritis, and perioperative considerations for total joint arthroplasty surgeons.","limitations":"This is a narrative review rather than a systematic review or meta-analysis, so it does not comprehensively quantify treatment effects. The evidence for GLP-1 agonists as disease-modifying agents for osteoarthritis is still emerging. Specific perioperative protocols for GLP-1 patients undergoing arthroplasty are based on limited data and expert opinion."},{"rthcId":"RPEP-08362","title":"Adropin/Tirzepatide Combination Mitigates Cardiac Metabolic Aberrations in a Rat Model of Polycystic Ovarian Syndrome, Implicating the Role of the AKT/GSK3β/NF-κB/NLRP3 Pathway.","authors":"Hegab, Islam Ibrahim; El-Horany, Hemat El-Sayed; Abd-Ellatif, Rania Nagi; Nasef, Nahla Anas; Okasha, Asmaa H; Emam, Marwa Nagy; Hassan, Shereen; Elseady, Walaa S; Radwan, Doaa A; ElEsawy, Rasha Osama; Hafez, Yasser Mostafa; Hassan, Maha Elsayed; Mansour, Nouran Mostafa; Abdelkader, Gamaleldien Elsayed; Fouda, Mohamed H; Abd El Maged, Amira M; Abdallah, Hanan M","year":2024,"journal":"International journal of molecular sciences, 26(1)","doi":"10.3390/ijms26010001","pmid":"39795860","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08363","title":"Warehouse-based, immunopeptidome-guided design of personalised peptide vaccines shows feasibility in clinical trial evaluation in CLL patients.","authors":"Heitmann, Jonas S; Jung, Susanne; Wacker, Marcel; Maringer, Yacine; Nelde, Annika; Bauer, Jens; Denk, Monika; Hoenisch-Gravel, Naomi; Richter, Marion; Oezbek, Melek T; Dubbelaar, Marissa L; Bilich, Tatjana; Pumptow, Marina; Martus, Peter; Illerhaus, Gerald; Denzlinger, Claudio; Steinbach, Francesca; Aulitzky, Walter-Erich; Müller, Martin R; Dörfel, Daniela; Rammensee, Hans-Georg; Salih, Helmut R; Walz, Juliane S","year":2024,"journal":"Frontiers in immunology, 15, 1482715","doi":"10.3389/fimmu.2024.1482715","pmid":"39660140","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The warehouse-based immunopeptidome-guided vaccine design was feasible for all 26 CLL patients, proving the personalized approach works at a practical level. Vaccination was well-tolerated, with local injection site reactions being the most common adverse event. However, only a few patients showed vaccine-induced T cell responses, attributed to immunosuppression from prior immuno-chemotherapy and the lack of a sufficiently potent adjuvant.\n\nA follow-up trial (NCT04688385) is now combining this warehouse approach with a more potent adjuvant and BTK inhibitor therapies that support T cell function, addressing the key limitations identified.","whyItMatters":"Personalized cancer vaccines have been limited by the time and cost of manufacturing custom peptides for each patient. This warehouse approach solves a major logistical problem: by pre-making a library of cancer-associated peptides, personalized vaccines can be assembled quickly for any patient. While the immune responses were disappointing in this immunocompromised population, the proof of feasibility is a significant advance for the field.","specificNumbers":"","methodology":"Phase II clinical trial (NCT02802943) enrolling 26 CLL patients in at least partial remission after 6 months of first-line immuno-chemotherapy. Each patient received a personalized vaccine assembled from a pre-manufactured peptide warehouse containing immunopeptidome-defined CLL-associated peptides, tailored to the patient's HLA type. Primary endpoint was immunogenicity (T cell responses), with secondary endpoints of safety and minimal residual disease (MRD) response.","limitations":"The primary limitation was the weak immune responses observed, attributed to patients' immunocompromised state after chemotherapy. The study lacked a control arm. Only patients in partial remission or better were enrolled, so the approach wasn't tested in patients with active disease. The peptide warehouse concept, while feasible, requires validation of clinical efficacy in a controlled trial with optimized adjuvants and less immunosuppressed patients."},{"rthcId":"RPEP-08364","title":"Association of single nucleotide polymorphisms in Neuropeptide Y (NPY) and Phosphoglycerate Mutase 2 (PGAM2) genes with growth traits in rabbits.","authors":"Helal, Mostafa; Ahmed, Marwa; Ragab, Mohamed; Ateya, Ahmed; Sakr, Shimaa","year":2024,"journal":"Tropical animal health and production, 56(7), 239","doi":"10.1007/s11250-024-04085-w","pmid":"39133441","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08365","title":"A review on inflammation modulating venom proteins/peptide therapeutics and their delivery strategies: A review.","authors":"Hemajha, Lakshmikanthan; Singh, Simran; Biji, Catherin Ann; Balde, Akshad; Benjakul, Soottawat; Nazeer, Rasool Abdul","year":2024,"journal":"International immunopharmacology, 142(Pt A), 113130","doi":"10.1016/j.intimp.2024.113130","pmid":"39278056","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08366","title":"Changes in glomerular filtration rate in patients with body mass index ≥35 kg/m2 treated with metabolic and bariatric surgery versus GLP-1 agonist at 1-year follow-up.","authors":"Henao-Carrillo, Diana Cristina; Jurado-Florez, Mayra Alejandra; Muñoz, Óscar Mauricio","year":2024,"journal":"Obesity science & practice, 10(4), e782","doi":"10.1002/osp4.782","pmid":"39130193","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08367","title":"The Antioxidant Effects of Trypsin-Hydrolysate Derived from Abalone Viscera and Fishery By-Products, and the Angiotensin-I Converting Enzyme (ACE) Inhibitory Activity of Its Purified Bioactive Peptides.","authors":"Heo, Jun-Ho; Kim, Eun-A; Kang, Nalae; Heo, Seong-Yeong; Ahn, Ginnae; Heo, Soo-Jin","year":2024,"journal":"Marine drugs, 22(10)","doi":"10.3390/md22100461","pmid":"39452868","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08368","title":"Regulation of antimicrobial peptides in Hermetia illucens in response to fungal exposure.","authors":"Herman, Neta; Vitenberg, Tzach; Hayouka, Zvi; Opatovsky, Itai","year":2024,"journal":"Scientific reports, 14(1), 29561","doi":"10.1038/s41598-024-80133-7","pmid":"39609510","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08369","title":"Targeting GLP-1 receptors to reduce nicotine use disorder: Preclinical and clinical evidence.","authors":"Herman, Rae J; Schmidt, Heath D","year":2024,"journal":"Physiology & behavior, 281, 114565","doi":"10.1016/j.physbeh.2024.114565","pmid":"38663460","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08370","title":"Oxytocin: physiology, pharmacology, and clinical application for labor management.","authors":"Hermesch, Amy C; Kernberg, Annessa S; Layoun, Vanessa R; Caughey, Aaron B","year":2024,"journal":"American journal of obstetrics and gynecology, 230(3S), S729-S739","doi":"10.1016/j.ajog.2023.06.041","pmid":"37460365","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08371","title":"Antiparasitic Evaluation of Aquiluscidin, a Cathelicidin Obtained from Crotalus aquilus, and the Vcn-23 Derivative Peptide against Babesia bovis, B. bigemina and B. ovata.","authors":"Hernández-Arvizu, Edwin Esaú; Asada, Masahito; Kawazu, Shin-Ichiro; Vega, Carlos Agustín; Rodríguez-Torres, Angelina; Morales-García, Rodrigo; Pavón-Rocha, Aldo J; León-Ávila, Gloria; Rivas-Santiago, Bruno; Mosqueda, Juan","year":2024,"journal":"Pathogens (Basel, Switzerland), 13(6)","doi":"10.3390/pathogens13060496","pmid":"38921794","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08372","title":"Narrative Review of Effects of Glucagon-Like Peptide-1 Receptor Agonists on Bone Health in People Living with Obesity.","authors":"Herrou, Julia; Mabilleau, Guillaume; Lecerf, Jean-Michel; Thomas, Thierry; Biver, Emmanuel; Paccou, Julien","year":2024,"journal":"Calcified tissue international, 114(2), 86-97","doi":"10.1007/s00223-023-01150-8","pmid":"37999750","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08373","title":"An update on migraine: Current and new treatment options.","authors":"Hervias, Teddy","year":2024,"journal":"JAAPA : official journal of the American Academy of Physician Assistants, 37(5), 1-7","doi":"10.1097/01.JAA.0000000000000014","pmid":"38662902","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08374","title":"Immunogenicity of Non-Mutated Ovarian Cancer-Specific Antigens.","authors":"Hesnard, Leslie; Thériault, Catherine; Cahuzac, Maxime; Durette, Chantal; Vincent, Krystel; Hardy, Marie-Pierre; Lanoix, Joël; Lavallée, Gabriel Ouellet; Humeau, Juliette; Thibault, Pierre; Perreault, Claude","year":2024,"journal":"Current oncology (Toronto, Ont.), 31(6), 3099-3121","doi":"10.3390/curroncol31060236","pmid":"38920720","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Of 91 previously identified tumor-specific antigens from ovarian cancer, 48 were selected for immunogenicity testing. When dendritic cells were pulsed with synthetic peptide versions of these antigens, they presented them at high levels on their surface. These peptide-loaded dendritic cells successfully expanded sizeable populations of CD8 T cells from healthy donors, confirming that the immune system can recognize and respond to these non-mutated cancer antigens.\n\nThe abundance of antigen presentation correlated with predicted HLA binding affinity, suggesting that computational tools can help predict which antigens will be most immunogenic.","whyItMatters":"Ovarian cancer has barely benefited from the immunotherapy revolution because suitable antigen targets have been hard to find. This study shows that non-mutated, epigenetically driven tumor antigens — presented as peptides — can effectively trigger immune responses, potentially opening the door to peptide-based vaccines or adoptive cell therapies for a cancer with few good treatment options.","specificNumbers":"91 tumor-specific antigens identified · 48 TSAs tested for immunogenicity · CD8 T cell expansion confirmed · Antigens from non-exonic genomic regions","methodology":"Researchers used proteogenomic analysis to identify tumor-specific antigens from primary epithelial ovarian cancer tumors. They synthesized 48 selected TSA peptides, pulsed them onto dendritic cells, and used targeted mass spectrometry to confirm presentation. Immunogenicity was tested by stimulating naïve CD8 T cells from healthy blood donors with TSA-pulsed dendritic cells, measuring expansion via MHC-peptide tetramer staining and TCR Vβ CDR3 sequencing.","limitations":"The study tested T cell responses from healthy donors, not ovarian cancer patients whose immune systems may be suppressed by the tumor microenvironment. All work was done in laboratory conditions (in vitro), so it remains unknown whether these antigens would trigger effective immune responses in patients. The fraction of EOC tumors expressing each antigen was not fully characterized."},{"rthcId":"RPEP-08375","title":"Altered expression of kisspeptin, dynorphin, and related neuropeptides in polycystic ovary syndrome: A cross-sectional study.","authors":"Hestiantoro, Andon; Noor Al Maghfira, Rachellina; Fathmasari, Ratna; Rahmala Febri, Ririn; Ongko Joyo, Ericko; Muharam, Raden; Pratama, Gita; Bowolaksono, Anom","year":2024,"journal":"International journal of reproductive biomedicine, 22(5), 395-404","doi":"10.18502/ijrm.v22i5.16440","pmid":"39091430","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The KISS1/PDYN (kisspeptin/prodynorphin) ratio was significantly higher in PCOS women compared to controls (p=0.02). Prodynorphin expression was significantly lower in the PCOS group (p<0.001). The positive correlation between KISS1 expression and the KISS1/PDYN ratio was much stronger in PCOS women (R=0.93, p<0.001) than controls (R=0.66, p<0.001).\n\nThe authors conclude that diminished dynorphin expression — not elevated kisspeptin alone — drives the increased ratio, and that this imbalance is highly specific to PCOS.","whyItMatters":"PCOS is the most common endocrine disorder in women of reproductive age, causing irregular periods, infertility, and metabolic problems. Understanding that dynorphin deficiency creates a neuropeptide imbalance could point toward new treatment approaches — potentially using drugs that boost dynorphin signaling or dampen kisspeptin to restore normal reproductive hormone pulsing.","specificNumbers":"","methodology":"Cross-sectional study of 20 women with PCOS and 20 without, enrolled at Cipto Mangunkusumo hospital in Jakarta, Indonesia (August–December 2022). Peripheral blood mRNA expression of KISS1, prodynorphin (PDYN), tachykinin-3 (neurokinin-B), leptin, and neuropeptide-Y was measured using quantitative PCR.","limitations":"Small sample size of 40 total women. The study measured peripheral blood mRNA, which may not perfectly reflect hypothalamic neuropeptide expression. Cross-sectional design cannot establish causation. Conducted at a single center in Indonesia, which may limit generalizability across ethnic populations."},{"rthcId":"RPEP-08376","title":"The GHSR1a antagonist LEAP2 regulates islet hormone release in a sex-specific manner.","authors":"Hewawasam, Nirun; Sarkar, Debalina; Bolton, Olivia; Delishaj, Blerinda; Almutairi, Maha; King, Aileen J F; Dereli, Ayse S; Despontin, Chloe; Gilon, Patrick; Reeves, Sue; Patterson, Michael; Hauge-Evans, Astrid C","year":2024,"journal":"The Journal of endocrinology, 263(2)","doi":"10.1530/JOE-24-0135","pmid":"39292603","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08377","title":"Clinical Implication of HIF-PH Inhibitor in Patients with Heart Failure, Chronic Kidney Disease, and Renal Anemia.","authors":"Hida, Yuki; Imamura, Teruhiko; Kinugawa, Koichiro","year":2024,"journal":"Journal of clinical medicine, 13(24)","doi":"10.3390/jcm13247619","pmid":"39768541","tags":["natriuretic-peptides"],"studyType":"observational-study","evidenceStrength":"moderate","keyFinding":"In 69 patients with both heart failure and renal anemia, HIF-PH inhibitors raised hemoglobin levels that had been declining during the prior 6 months without treatment. Starting hemoglobin was 9.2 g/dL after a decline from 10.5 g/dL in the pre-treatment period. Beyond correcting anemia, the treatment was associated with improvements in BNP levels (a peptide biomarker indicating heart failure severity), kidney function, and markers of systemic inflammation.\n\nThis suggests that treating renal anemia with HIF-PH inhibitors may have benefits beyond blood counts — potentially improving the interconnected cycle of heart failure, kidney disease, and anemia known as cardiorenal anemia syndrome.","whyItMatters":"Heart failure, chronic kidney disease, and anemia frequently occur together and worsen each other. BNP — a natriuretic peptide — is the primary biomarker used to track heart failure severity. Finding that treating the anemia component also improved BNP levels and kidney function suggests a positive cascade effect, where correcting one problem helps the others.","specificNumbers":"n=69 · median age 82 · baseline Hb 9.2 g/dL · baseline BNP 264 pg/mL · baseline eGFR 29.1 mL/min/1.73m² · 6-month follow-up","methodology":"This was a retrospective observational study of 69 patients with both heart failure and renal anemia who received HIF-PH inhibitors. Researchers compared clinical parameters during the 6 months before treatment (when hemoglobin was declining) to the 6 months during treatment. Outcomes included hemoglobin levels, BNP (B-type natriuretic peptide), estimated glomerular filtration rate, and inflammatory markers.","limitations":"This is a retrospective study without a control group, so improvements could be influenced by other treatment changes or natural disease fluctuation. The sample size of 69 patients is modest. The median age of 82 means results may not apply to younger heart failure patients. Some statistical values appear truncated in the abstract."},{"rthcId":"RPEP-08378","title":"Pharmacological Treatment of Binge Eating Disorder and Frequent Comorbid Diseases.","authors":"Himmerich, Hubertus; Bentley, Jessica; McElroy, Susan L","year":2024,"journal":"CNS drugs, 38(9), 697-718","doi":"10.1007/s40263-024-01111-1","pmid":"39096466","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08379","title":"An overview of site-specific methods for achieving antibody drug conjugates with homogenous drug to antibody ratio.","authors":"Hingorani, Dina V","year":2024,"journal":"Expert opinion on biological therapy, 24(1-2), 31-36","doi":"10.1080/14712598.2024.2305266","pmid":"38247196","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08380","title":"Screening and rational identification of a novel angiotensin-converting enzyme C-domain inhibitory peptide from Fabaceae food peptide library.","authors":"Ho, Tin-Yun; Lo, Hsin-Yi; Lu, Guan-Ling; Lin, Chia-Yu; Stevens, Mei-Li; Chen, Chiao-Che; Hsiang, Chien-Yun","year":2024,"journal":"Food chemistry, 452, 139540","doi":"10.1016/j.foodchem.2024.139540","pmid":"38723570","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08381","title":"Growth differentiation factor 15 is not modified after weight loss induced by liraglutide in South Asians and Europids with type 2 diabetes mellitus.","authors":"Hoekx, Carlijn A; Straat, Maaike E; Bizino, Maurice B; van Eyk, Huub J; Lamb, Hildebrandus J; Smit, Johannes W A; Jazet, Ingrid M; de Jager, Saskia C A; Boon, Mariëtte R; Martinez-Tellez, Borja","year":2024,"journal":"Experimental physiology, 109(8), 1292-1304","doi":"10.1113/EP091815","pmid":"38965822","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08382","title":"Conditional Cell Penetration of Masked CPPs by an ADEPT-like Approach.","authors":"Hofmann, Sarah; Dombrowsky, Carolin; Happel, Dominic; Dessin, Cedric; Cermjani, Egzon; Cica, Matijas; Avrutina, Olga; Sewald, Norbert; Neumann, Heinz; Kolmar, Harald","year":2024,"journal":"ACS chemical biology, 19(6), 1320-1329","doi":"10.1021/acschembio.4c00149","pmid":"38733564","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08383","title":"GLP-1 physiology in obesity and development of incretin-based drugs for chronic weight management.","authors":"Holst, Jens Juul","year":2024,"journal":"Nature metabolism, 6(10), 1866-1885","doi":"10.1038/s42255-024-01113-9","pmid":"39160334","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08384","title":"Design, Synthesis, and Structure-Activity Relationships of Novel Peptide Derivatives of the Severe Acute Respiratory Syndrome-Coronavirus-2 Spike-Protein that Potently Inhibit Nicotinic Acetylcholine Receptors.","authors":"Hone, Arik J; Santiago, Ulises; Harvey, Peta J; Tekarli, Bassel; Gajewiak, Joanna; Craik, David J; Camacho, Carlos J; McIntosh, J Michael","year":2024,"journal":"Journal of medicinal chemistry, 67(11), 9587-9598","doi":"10.1021/acs.jmedchem.4c00735","pmid":"38814877","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08385","title":"Sodium-Glucose Cotransporter-2 Inhibitors, Dulaglutide, and Risk for Dementia : A Population-Based Cohort Study.","authors":"Hong, Bin; Bea, Sungho; Ko, Hwa Yeon; Kim, Woo Jung; Cho, Young Min; Shin, Ju-Young","year":2024,"journal":"Annals of internal medicine, 177(10), 1319-1329","doi":"10.7326/M23-3220","pmid":"39186787","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In a propensity score-matched cohort using South Korean national health data (2010-2022), 12,489 patients initiating SGLT2 inhibitors (dapagliflozin or empagliflozin) and 1,075 patients initiating dulaglutide were compared. Over a median follow-up of 4.4 years:\n\n- Dementia events: 69 in the SGLT2 inhibitor group vs. 43 in the dulaglutide group\n- Risk difference: -0.91 percentage points (95% CI: -2.45 to 0.63) — not statistically significant\n- Risk ratio: 0.81 (95% CI: 0.56 to 1.16) — not statistically significant\n\nThe data were compatible with dementia risk being anywhere from 2.5 percentage points lower to 0.6 percentage points higher for SGLT2 inhibitors compared to dulaglutide.","whyItMatters":"Type 2 diabetes approximately doubles the risk of dementia, making neuroprotection a critical consideration when choosing diabetes medications. Both SGLT2 inhibitors and GLP-1 RAs have shown brain-protective signals in preclinical studies, but real-world comparative data have been scarce. This study — published in the prestigious Annals of Internal Medicine — provides some of the first head-to-head evidence comparing these two drug classes on dementia outcomes.","specificNumbers":"","methodology":"Target trial emulation study using nationwide South Korean health care data from the National Health Insurance Service (2010-2022). Patients aged 60+ with type 2 diabetes initiating SGLT2 inhibitors or dulaglutide were included. Propensity score matching (1:2 ratio) was used to adjust for confounders. The primary outcome was presumed clinical onset of dementia, defined as one year before diagnosis. Five-year risk ratios and risk differences were estimated using Cox models.","limitations":"The study has several important limitations: residual confounding is possible since HbA1c levels and diabetes duration were not adjusted for. The dulaglutide group was much smaller than the SGLT2 inhibitor group (1,075 vs 12,489), limiting statistical power. Newer GLP-1 RAs like semaglutide were not included. Dementia onset was estimated (one year before diagnosis) rather than directly measured. The South Korean population may not be representative of other ethnic groups. The study was observational, not a randomized trial."},{"rthcId":"RPEP-08386","title":"Role of glucagon-like peptide-1 receptor agonists in Alzheimer's disease and Parkinson's disease.","authors":"Hong, Chien-Tai; Chen, Jia-Hung; Hu, Chaur-Jong","year":2024,"journal":"Journal of biomedical science, 31(1), 102","doi":"10.1186/s12929-024-01090-x","pmid":"39501255","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In preclinical models (cell and animal studies), multiple GLP-1 receptor agonists demonstrated significant neuroprotective effects through several mechanisms: reducing neuroinflammation, enhancing autophagy (cellular cleanup), improving mitochondrial function, and preventing abnormal phosphorylation of disease-related proteins (tau in AD, α-synuclein in PD). These effects translated to improvements in cognitive and motor function in animal models.\n\nHowever, clinical trials investigating GLP-1RAs in AD, PD, mild cognitive impairment, psychiatric disorders, and diabetes have produced mixed results. Some trials showed cognitive or motor benefits while others did not demonstrate significant improvements over placebo. The review proposes that trial design issues — including patient selection, treatment duration, and outcome measures — may partly explain the inconsistent results.","whyItMatters":"With no disease-modifying treatments for Parkinson's and only recently approved (but controversial) options for Alzheimer's, finding new therapeutic approaches is critical. GLP-1 drugs are already widely prescribed and have established safety profiles, making them ideal candidates for repurposing. If the right clinical trial design can capture their neuroprotective effects, it could represent a major breakthrough for hundreds of millions of people at risk for neurodegenerative disease.","specificNumbers":"","methodology":"Narrative review synthesizing published preclinical research (in vitro and animal models) and clinical trial data on GLP-1 receptor agonists in Alzheimer's disease and Parkinson's disease. The review also covers the diabetes-neurodegeneration connection, GLP-1 signaling pathways in the brain, and proposes strategies for improved future trial design.","limitations":"As a narrative review, the selection and weighting of evidence may be subjective. The preclinical results, while promising, may not translate to humans due to fundamental differences in disease biology between animal models and human neurodegeneration. The mixed clinical trial results suggest that either the neuroprotective effects are modest in humans, that current trial designs are inadequate to detect them, or both. The optimal timing, dose, and duration of GLP-1RA treatment for neuroprotection are unknown."},{"rthcId":"RPEP-08387","title":"Therapeutic patterns and migraine disease burden in switchers of CGRP-targeted monoclonal antibodies - insights from the German NeuroTransData registry.","authors":"Hong, Ja Bin; Israel-Willner, Heike; Peikert, Andreas; Schanbacher, Peter; Tozzi, Viola; Köchling, Monika; Reuter, Uwe; Raffaelli, Bianca","year":2024,"journal":"The journal of headache and pain, 25(1), 90","doi":"10.1186/s10194-024-01790-7","pmid":"38825722","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08388","title":"Gut hormones and appetite regulation.","authors":"Hong, So-Hyeon; Choi, Kyung Mook","year":2024,"journal":"Current opinion in endocrinology, diabetes, and obesity, 31(3), 115-121","doi":"10.1097/MED.0000000000000859","pmid":"38511400","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08389","title":"Glycemic and Cost Outcomes among Hispanic/Latino People with Type 2 Diabetes in the USA Initiating Dulaglutide versus Basal Insulin: a Real-World Study.","authors":"Hoog, Meredith; Maldonado, Juan M; Wangia-Dixon, Ruth; Halpern, Rachel; Buysman, Erin; Gremel, Garrett W; Huang, Ahong; Konig, Manige","year":2024,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 15(4), 855-867","doi":"10.1007/s13300-024-01542-5","pmid":"38427164","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08390","title":"Adherence and treatment discontinuation of oral semaglutide and once-weekly semaglutide injection at 12 month follow-up: Japanese real-world data.","authors":"Horii, Takeshi; Masudo, Chikako; Takayanagi, Yui; Oikawa, Yoichi; Shimada, Akira; Mihara, Kiyoshi","year":2024,"journal":"Journal of diabetes investigation, 15(11), 1578-1584","doi":"10.1111/jdi.14265","pmid":"39243175","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08391","title":"Dual-modified penetratin peptides: Enhancing nucleic acid delivery through stapling and endosomal escape domain.","authors":"Horikoshi, Kanako; Miyamoto, Maho; Tsuchiya, Keisuke; Yokoo, Hidetomo; Demizu, Yosuke","year":2024,"journal":"Bioorganic & medicinal chemistry, 111, 117871","doi":"10.1016/j.bmc.2024.117871","pmid":"39133977","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08392","title":"Potent synergistic effects of dulaglutide and food restriction in prevention of olanzapine-induced metabolic adverse effects in a rodent model.","authors":"Horska, Katerina; Kucera, Jan; Drazanova, Eva; Kuzminova, Gabriela; Amchova, Petra; Hrickova, Maria; Ruda-Kucerova, Jana; Skrede, Silje","year":2024,"journal":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 176, 116763","doi":"10.1016/j.biopha.2024.116763","pmid":"38805968","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Olanzapine induced hyperphagia, weight gain, and increased triglycerides and HDL cholesterol in rats. Dulaglutide alone modestly decreased food intake but did not prevent weight gain or reverse olanzapine-induced lipid changes. Food restriction alone affected the obesity phenotype but not serum markers. However, the combination of dulaglutide + food restriction produced synergistic effects: weight loss, decreased feed efficiency, and lower total and HDL cholesterol.\n\nThe dramatic synergy between GLP-1RA treatment and dietary restriction suggests these interventions work through complementary mechanisms that amplify each other's benefits in the context of antipsychotic-induced metabolic dysfunction.","whyItMatters":"Antipsychotic medications are essential for managing conditions like schizophrenia and bipolar disorder, but their metabolic side effects — particularly weight gain and diabetes risk — significantly reduce life expectancy in psychiatric patients. Finding effective strategies to manage these side effects without stopping the antipsychotic is a major clinical need, and GLP-1 agonists combined with lifestyle support show real promise.","specificNumbers":"","methodology":"Female Sprague-Dawley rats received long-acting olanzapine and/or dulaglutide for 8 days. A pair-feeding protocol evaluated combined effects of dulaglutide and food restriction. Measurements included body weight, food consumption, lipid profile, gastrointestinal and adipose tissue-derived hormones, and fibroblast growth factor 21 serum levels.","limitations":"Short study duration (8 days) in rats — chronic effects may differ. Only female rats were studied. Olanzapine was given as a long-acting formulation, which may not replicate daily oral dosing patterns. The pair-feeding protocol is an artificial model of food restriction that may not reflect real-world dietary compliance in psychiatric patients. Only dulaglutide was tested; other GLP-1RAs may perform differently."},{"rthcId":"RPEP-08393","title":"Influence of Trp-Cage on the Function and Stability of GLP-1R Agonist Exenatide Derivatives.","authors":"Horváth, Dániel; Stráner, Pál; Taricska, Nóra; Fazekas, Zsolt; Menyhárd, Dóra K; Perczel, András","year":2024,"journal":"Journal of medicinal chemistry, 67(18), 16757-16772","doi":"10.1021/acs.jmedchem.4c01553","pmid":"39254428","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08394","title":"Efficacy and safety of atogepant, a small molecule CGRP receptor antagonist, for the preventive treatment of migraine: a systematic review and meta-analysis.","authors":"Hou, Min; Luo, Xiaofeng; He, Shuangshuang; Yang, Xue; Zhang, Qing; Jin, Meihua; Zhang, Pan; Li, Yang; Bi, Xiaoting; Li, Juan; Cheng, Caiyi; Xue, Qiang; Xing, Haiyan; Liu, Yao","year":2024,"journal":"The journal of headache and pain, 25(1), 116","doi":"10.1186/s10194-024-01822-2","pmid":"39030528","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08395","title":"Comparative Analysis of the Anti-Inflammatory Effects of Liraglutide and Dulaglutide.","authors":"Hou, Yi; Fan, Yini; Cheng, Yuan; Peng, Xiaoyue; Shan, Chunyan; Yang, Yanhui","year":2024,"journal":"International heart journal, 65(3), 548-556","doi":"10.1536/ihj.23-576","pmid":"38749748","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08396","title":"Gastroenteropancreatic Neuroendocrine Tumor with Peritoneal Metastasis: A Review of Current Management.","authors":"Hounschell, Corey A; Higginbotham, Simon; Al-Kasspooles, Mazin; Selby, Luke V","year":2024,"journal":"Cancers, 16(20)","doi":"10.3390/cancers16203472","pmid":"39456565","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08397","title":"The estrogenic reduction in water intake stimulated by dehydration involves estrogen receptor alpha and a potential role for GLP-1.","authors":"Howell, Julia A; Edwards, Andrea A; Santollo, Jessica","year":2024,"journal":"Physiology & behavior, 276, 114484","doi":"10.1016/j.physbeh.2024.114484","pmid":"38331374","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08398","title":"A novel heat-stable angiotensin-converting enzyme zinc-binding motif inhibitory peptide identified from corn silk.","authors":"Hsiang, Chien-Yun; Lo, Hsin-Yi; Lu, Guan-Ling; Liao, Pei-Yung; Ho, Tin-Yun","year":2024,"journal":"Journal of ethnopharmacology, 320, 117435","doi":"10.1016/j.jep.2023.117435","pmid":"37979812","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08399","title":"Molecular Display of the Animal Meta-Venome for Discovery of Novel Therapeutic Peptides.","authors":"Hsiao, Meng-Hsuan; Miao, Yang; Liu, Zixing; Schütze, Konstantin; Limjunyawong, Nathachit; Chien, Daphne Chun-Che; Monteiro, Wayne Denis; Chu, Lee-Shin; Morgenlander, William; Jayaraman, Sahana; Jang, Sung-Eun; Gray, Jeffrey J; Zhu, Heng; Dong, Xinzhong; Steinegger, Martin; Larman, H Benjamin","year":2024,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2024.05.27.595990","pmid":"38854075","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08400","title":"Cardiorenal effectiveness of empagliflozin vs. glucagon-like peptide-1 receptor agonists: final-year results from the EMPRISE study.","authors":"Htoo, Phyo T; Tesfaye, Helen; Schneeweiss, Sebastian; Wexler, Deborah J; Everett, Brendan M; Glynn, Robert J; Schmedt, Niklas; Koeneman, Lisette; Déruaz-Luyet, Anouk; Paik, Julie M; Patorno, Elisabetta","year":2024,"journal":"Cardiovascular diabetology, 23(1), 57","doi":"10.1186/s12933-024-02150-0","pmid":"38331813","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Compared with GLP-1 receptor agonists, empagliflozin was associated with:\n- Similar risk of MI or stroke: HR 0.99 (95% CI: 0.92-1.07)\n- 50% lower risk of heart failure hospitalization: HR 0.50 (0.44-0.56)\n- 10% lower risk of MACE: HR 0.90 (0.82-0.99)\n- 23% lower risk of CV mortality or HHF composite: HR 0.77 (0.69-0.86)\n- 25% lower risk of progression to ESKD in CKD stage 3-4 patients: HR 0.75 (0.60-0.94)\n\nAbsolute risk reductions were larger in older patients and those with baseline ASCVD or heart failure. Benefits did not differ by sex.","whyItMatters":"Clinicians treating type 2 diabetes must choose between SGLT-2 inhibitors and GLP-1 peptide agonists — both of which have cardiovascular benefits. Without head-to-head randomized trials, real-world evidence like EMPRISE fills a critical gap. These results suggest empagliflozin may be preferable for patients at high risk of heart failure or kidney disease, while GLP-1 agonists perform comparably for atherosclerotic events like heart attack and stroke. This informs personalized drug selection for millions of diabetes patients.","specificNumbers":"","methodology":"Retrospective propensity score-matched cohort study using US Medicare and commercial claims databases (2014-2019). 141,541 pairs of patients ≥18 years with type 2 diabetes who initiated empagliflozin or a GLP-1 RA were matched 1:1 using 143 baseline characteristics. Outcomes were evaluated using hazard ratios and rate differences per 1,000 person-years. Subgroup analyses examined effects by age, sex, baseline ASCVD, and heart failure history.","limitations":"This is an observational study using claims data, not a randomized trial, so residual confounding cannot be entirely eliminated despite matching on 143 variables. Claims data may misclassify outcomes or miss events not captured in billing records. The GLP-1 RA group included multiple agents (with varying efficacy), rather than comparing empagliflozin to a single GLP-1 RA. The study period (2014-2019) predates the widespread use of higher-dose semaglutide and tirzepatide. Cardiovascular mortality was identified from claims data, which has known limitations."},{"rthcId":"RPEP-08401","title":"A Review and Meta-Analysis of the Safety and Efficacy of Using Glucagon-like Peptide-1 Receptor Agonists.","authors":"Hu, En-Hao; Tsai, Ming-Lung; Lin, Yuan; Chou, Tien-Shin; Chen, Tien-Hsing","year":2024,"journal":"Medicina (Kaunas, Lithuania), 60(3)","doi":"10.3390/medicina60030357","pmid":"38541083","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08402","title":"Protein-peptide binding residue prediction based on protein language models and cross-attention mechanism.","authors":"Hu, Jun; Chen, Kai-Xin; Rao, Bing; Ni, Jing-Yuan; Thafar, Maha A; Albaradei, Somayah; Arif, Muhammad","year":2024,"journal":"Analytical biochemistry, 694, 115637","doi":"10.1016/j.ab.2024.115637","pmid":"39121938","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08403","title":"Characterization of GABAergic marker expression in prefrontal cortex in dexamethasone induced depression/anxiety model.","authors":"Hu, Ling; Qiu, Ming-Jing; Fan, Wen-Juan; Wang, Wan-Er; Liu, Shao-Hao; Liu, Xiao-Qi; Liu, Shi-Wei; Shen, Ze-Jin; Zheng, Ya-Fei; Liu, Guang-Chao; Jia, Zi-Yi; Wang, Xiao-Qing; Fang, Na","year":2024,"journal":"Frontiers in endocrinology, 15, 1433026","doi":"10.3389/fendo.2024.1433026","pmid":"39483976","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08404","title":"Topical Application of Cell-Penetrating Peptide Modified Anti-VEGF Drug Alleviated Choroidal Neovascularization in Mice.","authors":"Hu, Weinan; Cai, Wenting; Wu, Yan; Ren, Chengda; Yu, Donghui; Li, Tingting; Shen, Tianyi; Xu, Ding; Yu, Jing","year":2024,"journal":"International journal of nanomedicine, 19, 35-51","doi":"10.2147/IJN.S428684","pmid":"38187905","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08405","title":"Anti-aging effect of peptides on Caenorhabditis elegans: a meta-analysis.","authors":"Huang, Chao; Zhu, Ling; Zhang, Hui; Liu, Tongtong; Wang, Li; Wu, Gangcheng","year":2024,"journal":"Journal of the science of food and agriculture, 104(11), 6902-6913","doi":"10.1002/jsfa.13522","pmid":"38591735","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Peptide supplementation significantly extended the lifespan of C. elegans, reducing mortality risk by 46% (hazard ratio = 0.54, 95% CI: 0.47-0.62, p<0.05). Beyond living longer, peptide-treated worms also showed signs of healthier aging: pharyngeal pumping rate increased significantly (SMD = 1.64), bending frequency improved (SMD = 1.67), and lipofuscin accumulation — a marker of cellular aging — decreased dramatically (SMD = -4.48).\n\nSubgroup analysis revealed that doses of 0.1-1 mg/mL showed the best anti-aging effects (HR = 0.50, 95% CI: 0.38-0.65), suggesting an optimal dosing range for peptide-based lifespan extension.","whyItMatters":"While individual studies have suggested peptides may slow aging, this meta-analysis pools data from nine studies to provide stronger statistical evidence. The finding that peptides not only extend lifespan but also improve markers of healthy aging (movement, feeding, reduced cellular damage) is particularly meaningful — living longer matters most when quality of life is preserved.","specificNumbers":"2879 articles screened · 9 studies included · HR=0.54 (46% mortality reduction) · SMD=1.64 pumping rate · SMD=1.67 bending frequency · SMD=-4.48 lipofuscin · Optimal dose 0.1-1 mg/mL","methodology":"Systematic literature search across PubMed, Scopus, and Web of Science yielded 2,879 articles. After deduplication and quality assessment using the STAIR checklist, nine studies met inclusion criteria. Data were pooled using hazard ratios for survival and standardized mean differences for health markers. Subgroup analysis examined dose-response relationships.","limitations":"C. elegans is a simple nematode worm, so these results may not translate to mammals or humans. The nine included studies used different peptide types, sources, and experimental conditions. The meta-analysis combines heterogeneous peptide interventions, so the optimal specific peptides for anti-aging cannot be identified from these pooled results."},{"rthcId":"RPEP-08406","title":"Cellular Uptake of Cell-Penetrating Peptides Activated by Amphiphilic p-Sulfonatocalix[4]arenes.","authors":"Huang, Chusen; Liu, Yan-Cen; Oh, Hyeyoung; Guo, Dong-Sheng; Nau, Werner M; Hennig, Andreas","year":2024,"journal":"Chemistry (Weinheim an der Bergstrasse, Germany), 30(28), e202400174","doi":"10.1002/chem.202400174","pmid":"38456376","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08407","title":"Tumor Cell Lysate-Based Multifunctional Nanoparticles Facilitate Enhanced mRNA Delivery and Immune Stimulation for Melanoma Gene Therapy.","authors":"Huang, Jing; Wang, Kaiyu; Wu, Shan; Zhang, Jin; Chen, Xiayu; Lei, Sibei; Wu, Jieping; Men, Ke; Duan, Xingmei","year":2024,"journal":"Molecular pharmaceutics, 21(1), 267-282","doi":"10.1021/acs.molpharmaceut.3c00826","pmid":"38079527","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The MLSV system (DMP nanoparticles loaded with tumor cell lysate and modified with TAT-iRGD cell-penetrating peptide) achieved several key outcomes when loaded with Bim-encoding mRNA:\n\nDelivery: 68.6% transfection rate in B16 melanoma cells via caveolin-mediated endocytosis. Nanoparticle size was 191.4 nm with +47.8 mV surface charge.\n\nImmune activation: Induced dendritic cell maturation with increased CD80, CD86, and MHC-II expression both in vitro and in vivo.\n\nAnti-tumor efficacy: 87.3% growth inhibition in vitro; 78.7% tumor growth inhibition in subcutaneous B16 melanoma model; 63.3% inhibition in pulmonary metastatic B16 model in vivo.","whyItMatters":"Melanoma remains one of the deadliest skin cancers, especially when it metastasizes. mRNA-based cancer gene therapy has shown promise (building on mRNA vaccine technology), but getting mRNA into cancer cells efficiently is a major barrier. Cell-penetrating peptides solve this delivery problem. By combining mRNA-based gene therapy (killing cancer cells directly) with immunotherapy (activating the immune system via tumor lysate), this single nanoparticle platform attacks the tumor from two directions simultaneously — a strategy that could overcome resistance seen with either approach alone.","specificNumbers":"","methodology":"DMP cationic nanoparticles (DOTAP + mPEG-PCL self-assembly) were loaded with B16 melanoma cell lysate and surface-modified with the fused cell-penetrating peptide TAT-iRGD. Bim-encoding mRNA was loaded to form the MLSV/Bim complex. Characterization included size, zeta potential, and uptake mechanism analysis. Transfection efficiency was measured in B16 cells. Dendritic cell activation was assessed by CD80/CD86/MHC-II expression. Anti-tumor efficacy was tested in subcutaneous and pulmonary metastatic B16 melanoma models in mice.","limitations":"The B16 melanoma model is a murine (mouse) cancer, and results may not directly translate to human melanoma. The study did not test long-term survival outcomes or complete tumor regression — the reported metrics are growth inhibition rates. Potential immunogenicity of the peptide-modified nanoparticles with repeated dosing was not assessed. The tumor cell lysate approach requires a source of patient-specific tumor cells for personalized therapy, which adds complexity. Biodistribution, off-target effects, and potential toxicity in non-tumor tissues were not extensively characterized."},{"rthcId":"RPEP-08408","title":"Liraglutide ameliorates inflammation and fibrosis by downregulating the TLR4/MyD88/NF-κB pathway in diabetic kidney disease.","authors":"Huang, Linjing; Lin, Tingting; Shi, Meizhen; Wu, Peiwen","year":2024,"journal":"American journal of physiology. Regulatory, integrative and comparative physiology, 327(4), R410-R422","doi":"10.1152/ajpregu.00083.2024","pmid":"39133777","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Liraglutide protects against diabetic kidney disease by suppressing the TLR4/MyD88/NF-κB inflammatory signaling pathway. In cell culture, liraglutide reduced high-glucose-induced activation of this pathway, decreased inflammatory factors, and lowered extracellular matrix protein levels in kidney mesangial cells. When TLR4 was activated by LPS or overexpressed, it eliminated liraglutide's protective effects, confirming the pathway dependency. In diabetic mice, 8 weeks of liraglutide treatment significantly improved kidney damage, reduced inflammation and fibrosis. TLR4 knockout diabetic mice showed similar improvements, and liraglutide provided additional benefit even in TLR4 knockout mice.","whyItMatters":"Diabetic kidney disease is a leading cause of kidney failure worldwide. While GLP-1 receptor agonists like liraglutide are known to protect the kidneys, the mechanisms were unclear. This study identifies the specific inflammatory pathway (TLR4/MyD88/NF-κB) through which liraglutide exerts its renal protective effects, providing a mechanistic foundation for using this peptide drug to prevent kidney complications in diabetes.","specificNumbers":"8-week liraglutide treatment · reduced TLR4/MyD88/NF-κB signaling · decreased ECM proteins (fibronectin) · reduced inflammatory factors · TLR4-/- mice showed improved urine protein excretion","methodology":"The study combined in vitro and in vivo approaches. In vitro: rat mesangial cells were cultured in high glucose with liraglutide, TLR4 inhibitor (TAK242), TLR4 siRNA, TLR4 agonist (LPS), and TLR4 overexpression to dissect the signaling pathway. In vivo: streptozotocin-induced diabetic mice and TLR4 knockout diabetic mice were treated with liraglutide for 8 weeks, with assessment of kidney pathology, protein expression, inflammation, and fibrosis markers.","limitations":"This is a preclinical study in rodent cells and mouse models. The streptozotocin-induced diabetes model represents type 1 diabetes more closely than type 2, which is the primary clinical indication for liraglutide. The 8-week treatment duration in mice may not reflect long-term human kidney disease progression. Translation of these mechanistic findings to human DKD requires clinical validation."},{"rthcId":"RPEP-08409","title":"The antibacterial defence role of β-defensin in the seahorse testis.","authors":"Huang, Wei; Xiao, Wanghong; Qin, Geng; Lu, Zijian; Peng, Xiaoqian; Liu, Ying; Lin, Qiang; Sun, Jinhui","year":2024,"journal":"Fish & shellfish immunology, 155, 110022","doi":"10.1016/j.fsi.2024.110022","pmid":"39542066","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08410","title":"Gut hormone multi-agonists for the treatment of type 2 diabetes and obesity: advances and challenges.","authors":"Huang, Xianxian; Liu, Jing; Peng, Guangquan; Lu, Mingyue; Zhou, Zhongbo; Jiang, Neng; Yan, Zhiming","year":2024,"journal":"The Journal of endocrinology, 262(3)","doi":"10.1530/JOE-23-0404","pmid":"38916409","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review traces the development of three major classes of gut hormone multi-agonists: dual GLP-1/glucagon receptor agonists (first discovered 2009), dual GLP-1/GIP receptor agonists (first described 2013), and triple GLP-1/GIP/glucagon receptor agonists (first designed 2015).\n\nTirzepatide, a dual GLP-1/GIP agonist approved by the FDA for type 2 diabetes, outperformed both basal insulin and selective GLP-1 receptor agonists in HbA1c reduction. In non-diabetic individuals with obesity, tirzepatide achieved up to 22.5% weight loss — results comparable to certain bariatric surgeries.","whyItMatters":"With obesity and type 2 diabetes rates climbing worldwide, multi-agonist peptide drugs represent a paradigm shift in treatment. By targeting multiple hormone pathways simultaneously, these drugs achieve greater efficacy than single-target therapies. The success of tirzepatide has validated this approach, and triple agonists in development could push results even further.","specificNumbers":"","methodology":"This is a narrative review article that synthesizes published research on gut hormone multi-agonists. The authors surveyed the literature on the discovery, development, mechanisms of action, and clinical trial results for dual and triple receptor agonists targeting GLP-1, GIP, and glucagon receptors.","limitations":"As a review article, this paper does not present new experimental data. The long-term safety and efficacy of newer multi-agonists, particularly triple agonists, are still being established in clinical trials. The review may not capture the most recent trial results given the rapid pace of development in this field."},{"rthcId":"RPEP-08411","title":"Exenatide-Modified Deferoxamine-Based Nanoparticles Ameliorates Neurological Deficits in Parkinson's Disease Mice.","authors":"Huang, Yiming; Wang, Xinran; Li, Wenjing; Yue, Feng; Wang, Miao; Zhou, Feifan","year":2024,"journal":"International journal of nanomedicine, 19, 10401-10414","doi":"10.2147/IJN.S479670","pmid":"39430307","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Nanoparticles (~100 nm) coated with exendin-4 (a GLP-1 peptide) and loaded with deferoxamine (an iron chelator) successfully crossed the blood-brain barrier and reached the brain in a Parkinson's disease mouse model. The Ex-4@DFO NPs achieved synergistic neuroprotection through two mechanisms: iron chelation (removing toxic iron accumulation) and GLP-1 receptor-mediated anti-inflammatory effects.\n\nIn MPTP-induced PD mice, the nanoparticles significantly reduced dopaminergic neuron loss and neuroinflammation in the substantia nigra, and improved mobility deficits. In vitro, the particles protected neuronal mitochondria and reduced inflammatory factor release from microglial cells.","whyItMatters":"Parkinson's disease involves both iron accumulation and neuroinflammation in the brain, but treating it with iron chelators has been limited by their toxicity and poor brain penetration. Using the GLP-1 peptide exendin-4 as both a targeting molecule (to cross the blood-brain barrier) and a therapeutic agent (anti-inflammatory) is an elegant dual-function approach. This demonstrates how peptides can serve as intelligent delivery systems — not just cargo — in nanoparticle-based neurotherapeutics.","specificNumbers":"~100 nm particle size · BBB penetration confirmed · Dopaminergic neuron loss reduced · Neuroinflammation mitigated · Mobility deficits improved · Dual mechanism (iron chelation + anti-inflammation)","methodology":"Ex-4@DFO nanoparticles were synthesized by double emulsion technique. Characterization included particle size, morphology, and drug encapsulation efficiency. In vitro testing used BV-2 microglial and SH-SY5Y neuronal cells for biocompatibility, cellular uptake, and cytoprotection. In vivo efficacy was tested in MPTP-induced Parkinson's mice using near-infrared II fluorescence imaging for brain targeting, immunofluorescence for dopaminergic neuron quantification, and behavioral mobility tests.","limitations":"The MPTP mouse model produces acute dopaminergic neuron death, which differs from the slowly progressive neurodegeneration in human Parkinson's disease. Long-term safety of repeated nanoparticle brain delivery was not assessed. The specific contribution of exendin-4's anti-inflammatory effect versus deferoxamine's iron chelation was not separately quantified. The blood-brain barrier crossing mechanism and efficiency need more detailed characterization."},{"rthcId":"RPEP-08412","title":"Long-term safety and efficacy of glucagon-like peptide-1 receptor agonists in individuals with obesity and without type 2 diabetes: A global retrospective cohort study.","authors":"Huang, Yu-Nan; Liao, Wen-Ling; Huang, Jing-Yang; Lin, Yu-Jung; Yang, Shun-Fa; Huang, Chieh-Chen; Wang, Chung-Hsing; Su, Pen-Hua","year":2024,"journal":"Diabetes, obesity & metabolism, 26(11), 5222-5232","doi":"10.1111/dom.15869","pmid":"39171569","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08413","title":"Exploring bioactive compounds in chickpea and bean aquafaba: Insights from glycomics and peptidomics analyses.","authors":"Huang, Yu-Ping; Masarweh, Chad; Paviani, Bruna; Mills, David A; Barile, Daniela","year":2024,"journal":"Food chemistry, 460(Pt 2), 140635","doi":"10.1016/j.foodchem.2024.140635","pmid":"39111140","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Aquafaba (the cooking water from chickpeas and beans) contains dozens of bioactive peptides and oligosaccharides. Using advanced mass spectrometry, the researchers identified 78 oligosaccharides in chickpea aquafaba and 67 in common bean aquafaba. They also discovered several γ-glutamyl peptides with known anti-inflammatory and flavor-enhancing (kokumi) properties, including γ-Glu-Phe and γ-Glu-Tyr in chickpea aquafaba, and γ-Glu-S-methyl-Cys and γ-Glu-Leu in bean aquafaba. The oligosaccharides also showed prebiotic activity, promoting the growth of beneficial gut bacteria.","whyItMatters":"Aquafaba is typically discarded as a cooking byproduct but has gained popularity as an egg substitute in vegan cooking. This study reveals it also contains bioactive peptides and prebiotics that could have health benefits. Finding anti-inflammatory peptides and gut-friendly sugars in a food waste product aligns with food sustainability goals and could support health claims for legume-based foods.","specificNumbers":"","methodology":"The researchers analyzed chickpea and common bean aquafaba using high-performance anion-exchange chromatography to quantify known oligosaccharides, and LC-MS/MS (liquid chromatography tandem mass spectrometry) to identify additional compounds. They used dimethyl labeling to distinguish between α- and γ-glutamyl peptides. Prebiotic activity was tested by measuring whether the oligosaccharides could promote growth of three probiotic bacterial strains in culture.","limitations":"This is a laboratory analytical study — the bioactive properties of the identified peptides are inferred from the existing literature rather than directly tested in this study. The prebiotic effects were demonstrated only in bacterial growth assays, not in human or animal gut models. Concentrations of bioactive compounds in aquafaba may vary depending on cooking methods, bean variety, and water ratios."},{"rthcId":"RPEP-08414","title":"Protective role of ghrelin against 6PPD-quinone-induced neurotoxicity in zebrafish larvae (Danio rerio) via the GHSR pathway.","authors":"Huang, Zhengwei; Chen, Congcong; Guan, Kaiyu; Xu, Shengnan; Chen, Xiaoyu; Lin, Yihao; Li, Xi; Shan, Yunfeng","year":2024,"journal":"Ecotoxicology and environmental safety, 285, 117031","doi":"10.1016/j.ecoenv.2024.117031","pmid":"39341137","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08415","title":"Renal Effects of Combination Phosphodiesterase V Inhibition and Low-Dose B-Type Natriuretic Peptide in Acute Heart Failure: A Randomized Clinical Trial.","authors":"Hubers, Scott A; Benike, Sherry L; Johnson, Bradley K; McKie, Paul M; Scott, Christopher; Chen, Horng H","year":2024,"journal":"Circulation. Heart failure, 17(12), e011761","doi":"10.1161/CIRCHEARTFAILURE.124.011761","pmid":"39513267","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 67 patients hospitalized with acute heart failure and renal dysfunction, both BNP alone and BNP combined with sildenafil (PDE-V inhibitor) significantly increased plasma cGMP at 24 hours: +25.6% with BNP and +60.8% with BNP/sildenafil versus -13.5% with standard care (P=0.001).\n\nHowever, this biochemical response did not translate to clinical improvement. The coprimary endpoints showed no significant differences: eGFR change was 0% (standard care) vs 0% (BNP) vs -8.8% (BNP/sildenafil) (P=0.60), and BUN change was -1.4% vs -5.9% vs +6.9% (P=0.38). Urinary sodium and cGMP excretion also did not improve. Hypotension was more common in the BNP/sildenafil group, representing a safety concern.","whyItMatters":"Cardiorenal syndrome — simultaneous heart and kidney failure — is one of the deadliest complications of acute heart failure, with no specific approved therapy. BNP was a biologically rational choice because it's the body's own cardiac peptide hormone designed to protect the kidneys. The hypothesis that PDE-V upregulation in heart failure degrades the cGMP signal needed for kidney protection was mechanistically sound. This well-designed negative result is important because it closes a therapeutic hypothesis and redirects research effort toward other approaches.","specificNumbers":"","methodology":"Open-label randomized clinical trial (NCT00972569) with 67 patients hospitalized for acute heart failure with renal dysfunction, randomized to three arms: standard care, low-dose IV BNP (0.005 µg/kg/min), or combination BNP plus sildenafil (25 mg every 12 hours) for 48 hours. Coprimary endpoints were percent change in eGFR and BUN from baseline to 48 hours. Secondary endpoints included plasma cGMP, urinary sodium, and urinary cGMP excretion.","limitations":"The study was open-label (not blinded), which could introduce bias in clinical management. The sample size of 67 patients limits statistical power for detecting modest treatment effects. Only one BNP dose was tested — higher doses might produce different results but were avoided due to hypotension risk. The 48-hour treatment duration may be too short for renal effects to manifest. The patient population was heterogeneous, and specific heart failure subtypes may respond differently."},{"rthcId":"RPEP-08416","title":"Acute Pancreatitis Likely Due to Semaglutide.","authors":"Hughes, Katie; Sumaruth, Yovan Ram Kurrun; Mohammed, Elmahi; Sant Bakshsingh, Vibhootee","year":2024,"journal":"Cureus, 16(9), e69844","doi":"10.7759/cureus.69844","pmid":"39308839","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08417","title":"Cell penetration of oxadiazole-containing macrocycles.","authors":"Huh, Sungjoon; Batistatou, Nefeli; Wang, Jing; Saunders, George J; Kritzer, Joshua A; Yudin, Andrei K","year":2024,"journal":"RSC chemical biology, 5(4), 328-334","doi":"10.1039/d3cb00201b","pmid":"38576720","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Oxadiazole-containing (Odz) cyclic peptides showed high cell penetration that depended on the position of specific side chains and the chloroalkane tag used for detection. NMR analysis revealed these macrocycles adopt a β-turn conformation. Intriguingly, despite high cell penetration in living cells, they showed low passive permeability in artificial membrane assays.\n\nThis discrepancy suggests these cyclic peptides enter cells through an active or energy-dependent mechanism rather than simply diffusing through cell membranes — an important finding for understanding and designing cell-penetrant macrocyclic peptides.","whyItMatters":"Getting peptide drugs inside cells is one of the biggest challenges in drug development. Cyclic peptides are promising drug candidates because of their stability and ability to block protein-protein interactions, but most cannot cross cell membranes. This study shows that incorporating oxadiazole groups into cyclic peptides can enable cell entry, and the finding that entry occurs through a non-passive mechanism opens new strategies for designing membrane-permeable peptide therapeutics.","specificNumbers":"β-turn conformation confirmed by NMR · High cell penetration observed · Low passive permeability on artificial membranes · Side chain position-dependent activity","methodology":"Researchers synthesized oxadiazole-containing cyclic peptides with varying side chain positions and chloroalkane tags. Cell penetration was measured using the Chloroalkane Penetration Assay (CAPA) in living cells. Passive permeability was tested on artificial membranes (PAMPA or similar). Solution NMR spectroscopy was used to determine the three-dimensional conformation of the cyclic peptides.","limitations":"The study focused on a specific structural framework (oxadiazole-containing macrocycles), and results may not generalize to all cyclic peptides. The mechanism of active cell entry was not fully elucidated. No biological activity or target engagement was demonstrated — only cell penetration. The chloroalkane tag required for the assay may influence the peptides' behavior."},{"rthcId":"RPEP-08418","title":"To the Brain and Beyond: Neurological Implications of Glucagon-Like Peptide-1 Receptor Agonists.","authors":"Hunter Guevara, Lindsay R; Beam, W Brian B; Pasternak, Jeffrey J","year":2024,"journal":"Journal of neurosurgical anesthesiology, 36(4), 278-282","doi":"10.1097/ANA.0000000000000985","pmid":"39082303","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08419","title":"mRNA Display in Cell Lysates Enables Identification of Cyclic Peptides Targeting the BRD3 Extraterminal Domain.","authors":"Hurd, Catherine A; Bush, Jacob T; Powell, Andrew J; Walport, Louise J","year":2024,"journal":"Angewandte Chemie (International ed. in English), 63(38), e202406414","doi":"10.1002/anie.202406414","pmid":"38899853","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08420","title":"Association of glucagon-like peptide-1 receptor agonists with suicidal ideation and self-injury in individuals with diabetes and obesity: a propensity-weighted, population-based cohort study.","authors":"Hurtado, Isabel; Robles, Celia; Peiró, Salvador; García-Sempere, Aníbal; Sanfélix-Gimeno, Gabriel","year":2024,"journal":"Diabetologia, 67(11), 2471-2480","doi":"10.1007/s00125-024-06243-z","pmid":"39103719","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08421","title":"Semaglutide ameliorated autism-like behaviors and DNA repair efficiency in male BTBR mice by recovering DNA repair gene expression.","authors":"Hussein, Marwa H; Alameen, Alaa A; Ansari, Mushtaq A; AlSharari, Shakir D; Ahmad, Sheikh F; Attia, Mohamed S M; Sarawi, Wedad S; Nadeem, Ahmed; Bakheet, Saleh A; Attia, Sabry M","year":2024,"journal":"Progress in neuro-psychopharmacology & biological psychiatry, 135, 111091","doi":"10.1016/j.pnpbp.2024.111091","pmid":"39032854","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08422","title":"Empagliflozin attenuates hypoxia-induced heart failure of zebrafish embryos via influencing MMP13 expression.","authors":"Huttunen, R; Haapanen-Saaristo, A-M; Hjelt, A; Jokilammi, A; Paatero, I; Järveläinen, H","year":2024,"journal":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 180, 117453","doi":"10.1016/j.biopha.2024.117453","pmid":"39332186","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08423","title":"Bioproduction Platform to Generate Functionalized Disulfide-Constrained Peptide Analogues.","authors":"Hwang, Sunhee; Balana, Aaron T; Martin, Bryan; Clarkson, Michael; Di Lello, Paola; Wu, Hao; Li, Yanjie; Fuhrmann, Jakob; Dagdas, Yavuz; Holder, Patrick; Schroeder, Christina I; Miller, Stephen E; Gao, Xinxin","year":2024,"journal":"ACS bio & med chem Au, 4(4), 190-203","doi":"10.1021/acsbiomedchemau.4c00026","pmid":"39184057","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08424","title":"Glucagon-like peptide-1 class drugs show clear protective effects in Parkinson's and Alzheimer's disease clinical trials: A revolution in the making?","authors":"Hölscher, Christian","year":2024,"journal":"Neuropharmacology, 253, 109952","doi":"10.1016/j.neuropharm.2024.109952","pmid":"38677445","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08425","title":"Association of anti-calcitonin gene-related peptide with other monoclonal antibodies for different diseases: A multicenter, prospective, cohort study.","authors":"Iannone, Luigi Francesco; Romozzi, Marina; Russo, Antonio; Saporito, Gennaro; De Santis, Federico; Ornello, Raffaele; Sances, Grazia; Vaghi, Gloria; Tassorelli, Cristina; Albanese, Maria; Guerzoni, Simona; Casalena, Alfonsina; Vollono, Catello; Calabresi, Paolo; Prudenzano, Maria Pia; Mampreso, Edoardo; Volta, Giorgio Dalla; Valente, Maria Rosaria; Avino, Gianluca; Chiarugi, Alberto; Sacco, Simona; Pistoia, Francesca","year":2024,"journal":"European journal of neurology, 31(12), e16450","doi":"10.1111/ene.16450","pmid":"39285638","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Anti-CGRP monoclonal antibodies were safe and effective when used alongside other monoclonal antibodies for different conditions. In 38 migraine patients taking both an anti-CGRP mAb and another mAb, monthly headache days decreased significantly at 3 months (p<0.0001) and 6 months (p<0.001), along with improvements in disability (MIDAS) and impact (HIT-6) scores. Only 15.8% of patients experienced mild adverse events from the combination, and only one patient discontinued due to side effects. At 6 months, 48.3% of patients reported meaningful improvement on the global impression of change scale.","whyItMatters":"Many migraine patients also have other conditions requiring monoclonal antibody therapy (e.g., autoimmune diseases, cancer). Until now, there was almost no data on whether combining anti-CGRP antibodies with other biologics was safe. This real-world study provides reassuring evidence that these combinations are well tolerated, allowing patients to receive optimal treatment for multiple conditions simultaneously without compromising migraine management.","specificNumbers":"n=38 · MHDs decreased at 3 months (p<0.0001) · MHDs decreased at 6 months (p<0.001) · 48.3% PGIC ≥5 at 6 months · 15.8% mild AEs · 1 discontinuation for AEs · 71.1% added anti-CGRP to existing mAb","methodology":"This multicenter prospective cohort study used data from the Italian Headache Registry. Patients receiving both an anti-CGRP monoclonal antibody and another monoclonal antibody for a different disease were followed for 6 months. Effectiveness was measured by monthly headache days, MIDAS disability score, HIT-6 impact score, and patient global impression of change. Adverse events were systematically recorded.","limitations":"The sample size of 38 patients is small, limiting statistical power for detecting rare adverse events from the combination. There was no control group of patients taking anti-CGRP mAbs alone. The study did not detail which specific other monoclonal antibodies were used or for which conditions. The 6-month follow-up may be insufficient to detect long-term safety concerns from dual biologic therapy."},{"rthcId":"RPEP-08426","title":"Predictive Value of NT-proBNP, FGF21, Galectin-3 and Copeptin in Advanced Heart Failure in Patients with Preserved and Mildly Reduced Ejection Fraction and Type 2 Diabetes Mellitus.","authors":"Ianos, Raluca Diana; Iancu, Mihaela; Pop, Calin; Lucaciu, Roxana Liana; Hangan, Adriana Corina; Rahaian, Rodica; Cozma, Angela; Negrean, Vasile; Mercea, Delia; Procopciuc, Lucia Maria","year":2024,"journal":"Medicina (Kaunas, Lithuania), 60(11)","doi":"10.3390/medicina60111841","pmid":"39597026","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08427","title":"Impact of ADA Guidelines and Medication Shortage on GLP-1 Receptor Agonists Prescribing Trends in the UK: A Time-Series Analysis with Country-Specific Insights.","authors":"Ibrahim, Ahmed R N; Orayj, Khalid M","year":2024,"journal":"Journal of clinical medicine, 13(20)","doi":"10.3390/jcm13206256","pmid":"39458206","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08428","title":"Clinical Evaluation of the Efficacy of Itch-Relief Moisturizers Containing Maltotetraose for Dry, Itchy, and Sensitive Skin.","authors":"Ichikawa, Eri; Inoue, Akinori; Matsuzaki, Kenichi; Kaneda, Sumi; Naito, Atsushi; Yokoyama, Mihoko","year":2024,"journal":"Skinmed, 22(3), 187-196","doi":null,"pmid":"39090011","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08429","title":"Potential Impact of Bioactive Peptides from Foods in the Treatment of Hypertension.","authors":"Ichim, Natalia; Marín, Francisco; Orenes-Piñero, Esteban","year":2024,"journal":"Molecular nutrition & food research, 68(14), e2400084","doi":"10.1002/mnfr.202400084","pmid":"38923775","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08430","title":"Effects of glucagon-like peptide-1 receptor agonists on spermatogenesis-related gene expression in mouse testis and testis-derived cell lines.","authors":"Iida, Masashi; Asano, Atsushi","year":2024,"journal":"The Journal of veterinary medical science, 86(5), 555-562","doi":"10.1292/jvms.24-0042","pmid":"38556323","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08431","title":"Correlations Between Plasma BNP Level and Risk of Thrombotic-Hemorrhagic Events After Left Atrial Appendage Closure.","authors":"Imamura, Teruhiko; Kataoka, Naoya; Tanaka, Shuhei; Ueno, Hiroshi; Kinugawa, Koichiro; Nakashima, Masaki; Yamamoto, Masanori; Sago, Mitsuru; Chatani, Ryuki; Asami, Masahiko; Hachinohe, Daisuke; Naganuma, Toru; Ohno, Yohei; Tani, Tomoyuki; Okamatsu, Hideharu; Mizutani, Kazuki; Watanabe, Yusuke; Izumo, Masaki; Saji, Mike; Mizuno, Shingo; Kubo, Shunsuke; Shirai, Shinichi; Hayashida, Kentaro","year":2024,"journal":"Journal of clinical medicine, 13(20)","doi":"10.3390/jcm13206232","pmid":"39458182","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 937 patients who underwent LAAC (98% successful implantation rate), the common logarithm of baseline plasma BNP was independently associated with the composite primary outcome (death or stroke/bleeding events) with an adjusted hazard ratio of 1.46 (95% CI: 1.06-2.18, p = 0.043). A calculated BNP cutoff of 133 pg/mL significantly stratified outcomes: 29% vs 21% cumulative incidence of the primary outcome at 2 years (p = 0.004). Over a median follow-up of 366 days, 148 patients experienced a primary outcome event.","whyItMatters":"LAAC is performed to prevent stroke in atrial fibrillation patients who can't take blood thinners. But some patients remain at high risk even after the procedure. This study shows that the natriuretic peptide BNP — a simple, widely available blood test — can identify which patients are at highest risk, enabling more personalized post-procedure monitoring and management.","specificNumbers":"","methodology":"Multi-center prospective registry study (OCEAN-LAAC registry) in Japan. 937 patients with non-valvular atrial fibrillation who underwent percutaneous left atrial appendage closure were included. Patients without baseline BNP levels or on hemodialysis were excluded. Cox regression assessed the prognostic impact of baseline BNP on death or stroke/bleeding events. ROC analysis determined the optimal BNP cutoff.","limitations":"Observational registry data cannot establish causation. The study was conducted exclusively in Japanese patients, which may limit generalizability to other populations. BNP was measured only at baseline — changes over time were not assessed. The study could not determine whether BNP-guided management would improve outcomes. The 133 pg/mL cutoff needs external validation."},{"rthcId":"RPEP-08432","title":"Visualization of the Plasmid DNA Delivery System by Complementary Fluorescence Labeling of Arginine-Rich Peptides.","authors":"Imayoshi, Ayumi; Yokoo, Hidetomo; Kawaguchi, Masashi; Tsubaki, Kazunori; Oba, Makoto","year":2024,"journal":"Chemical & pharmaceutical bulletin, 72(10), 856-861","doi":"10.1248/cpb.c24-00479","pmid":"39370260","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08433","title":"Effects of Hydrolyzed Collagen as a Dietary Supplement on Fibroblast Activation: A Systematic Review.","authors":"Inacio, Pedro Augusto Querido; Chaluppe, Felipe Augusto; Aguiar, Gerson Ferreira; Coelho, Carly de Faria; Vieira, Rodolfo P","year":2024,"journal":"Nutrients, 16(11)","doi":"10.3390/nu16111543","pmid":"38892477","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08434","title":"The Effects of Collagen Peptides as a Dietary Supplement on Muscle Damage Recovery and Fatigue Responses: An Integrative Review.","authors":"Inacio, Pedro Augusto Querido; Gomes, Yasmin Salgado Mussel; de Aguiar, Ana Julia Nunes; Lopes-Martins, Pedro Sardinha Leonardo; Aimbire, Flávio; Leonardo, Patrícia Sardinha; Sá Filho, Alberto Souza; Lopes-Martins, Rodrigo Alvaro B","year":2024,"journal":"Nutrients, 16(19)","doi":"10.3390/nu16193403","pmid":"39408370","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08435","title":"Water-Based Synthesis of β-Sheet-Like Supramolecular Metallohydrogel Organized by Using a Native Ultrashort Peptide Sequence.","authors":"Inada, Asuka; Motomura, Aki; Oshima, Tatsuya","year":2024,"journal":"Chemistry (Weinheim an der Bergstrasse, Germany), 30(11), e202303160","doi":"10.1002/chem.202303160","pmid":"38016928","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08436","title":"Antidepressant-like and antistress effects of the ACTH(4-10) synthetic analogs Semax and Melanotan II on male rats in a model of chronic unpredictable stress.","authors":"Inozemtseva, Ludmila S; Yatsenko, Ksenia A; Glazova, Natalya Yu; Kamensky, Andrey A; Myasoedov, Nikolai F; Levitskaya, Natalia G; Grivennikov, Igor A; Dolotov, Oleg V","year":2024,"journal":"European journal of pharmacology, 984, 177068","doi":"10.1016/j.ejphar.2024.177068","pmid":"39442746","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08437","title":"Eptinezumab for the preventive treatment of episodic and chronic migraine: a narrative review.","authors":"Irimia, Pablo; Santos-Lasaosa, Sonia; Pozo-Rosich, Patricia; Leira, Rogelio; Pascual, Julio; Láinez, José Miguel","year":2024,"journal":"Frontiers in neurology, 15, 1355877","doi":"10.3389/fneur.2024.1355877","pmid":"38523607","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08438","title":"Hypoxic culture enhances the antimicrobial activity of amnion-derived mesenchymal stem cells, thereby reducing bacterial load and promoting wound healing in diabetic mice.","authors":"Ishii, Riku; Ohnishi, Shunsuke; Hojo, Masahiro; Ishikawa, Kosuke; Funayama, Emi; Miura, Takahiro; Okubo, Naoto; Okada, Kazufumi; Yamamoto, Yuhei; Maeda, Taku","year":2024,"journal":"Biochemical and biophysical research communications, 739, 150903","doi":"10.1016/j.bbrc.2024.150903","pmid":"39531904","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Amnion-derived mesenchymal stem cells (AMSCs) cultured under hypoxic conditions (1% O2) produced higher levels of the antimicrobial peptide LL-37 compared to normal oxygen conditions (21% O2). The hypoxic conditioned medium significantly inhibited S. aureus growth in vitro.\n\nWhen delivered as a hydrogel to S. aureus-infected skin wounds in diabetic mice, the hypoxic conditioned medium reduced bacterial counts in the wounds and facilitated wound closure. This dual antimicrobial and wound-healing effect was mediated at least in part by the elevated LL-37 levels.","whyItMatters":"Diabetic foot ulcers affect millions of people and are a leading cause of non-traumatic limb amputation. Antibiotic resistance makes treating infected wounds increasingly difficult. This study shows that stem cells can be stimulated to produce natural antimicrobial peptides by simply changing their growth conditions — no genetic engineering needed. LL-37 is a human cathelicidin peptide that bacteria have difficulty developing resistance to, making this approach potentially more sustainable than conventional antibiotics.","specificNumbers":"","methodology":"AMSCs were cultured under normal (21% O2) or hypoxic (1% O2) conditions, and the conditioned medium was collected. LL-37 levels were measured. Antimicrobial activity was tested against S. aureus in vitro. For in vivo testing, skin wounds were created on diabetic mice, infected with S. aureus, and treated with hydrogels containing the conditioned medium. Bacterial counts and wound closure were monitored.","limitations":"This is a mouse model study, and diabetic wound healing in mice differs from humans in important ways. The conditioned medium contains many factors besides LL-37, so the contribution of LL-37 specifically was not isolated. The study tested only S. aureus — effectiveness against other wound pathogens is unknown. Long-term outcomes, optimal dosing frequency, and scalability of conditioned medium production were not addressed."},{"rthcId":"RPEP-08439","title":"Effect of switching from dulaglutide to tirzepatide on blood glucose and renal function.","authors":"Ishimura, Atsushi; Kumakura, Hiroyoshi","year":2024,"journal":"Drug discoveries & therapeutics, 18(5), 323-324","doi":"10.5582/ddt.2024.01061","pmid":"39462543","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08440","title":"Enhancement of Oral Bioavailability of Protein and Peptide by Polysaccharide-based Nanoparticles.","authors":"Islam, Md Moidul; Raikwar, Sarjana","year":2024,"journal":"Protein and peptide letters, 31(3), 209-228","doi":"10.2174/0109298665292469240228064739","pmid":"38509673","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08441","title":"The Roles of Neuropeptide Y in Respiratory Disease Pathogenesis via the Airway Immune Response.","authors":"Itano, Junko; Kiura, Katsuyuki; Maeda, Yoshinobu; Miyahara, Nobuaki","year":2024,"journal":"Acta medica Okayama, 78(2), 95-106","doi":"10.18926/AMO/66912","pmid":"38688827","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Neuropeptide Y, a 36-amino-acid polypeptide neurotransmitter, acts through a family of G-protein-coupled receptors with six subtypes (Y1-Y6), of which Y1, Y2, Y4, and Y5 are functional in humans. The Y1 receptor plays particularly important roles in immune responses across multiple organs including the respiratory system.\n\nNPY and the Y1 receptor have critical roles in the pathogenesis of asthma, COPD, and idiopathic pulmonary fibrosis. Notably, the effects of NPY on airway immune responses and disease pathogenesis differ among these respiratory conditions, indicating that NPY's influence is disease-specific rather than following a single unified mechanism.","whyItMatters":"Chronic respiratory diseases like asthma and COPD affect hundreds of millions of people worldwide, and current treatments don't work for everyone. By mapping out how a single neuropeptide influences lung immunity differently across diseases, this review highlights NPY receptors as potential therapeutic targets. Drugs that modulate NPY signaling could offer new treatment strategies tailored to specific respiratory conditions.","specificNumbers":"","methodology":"This is a narrative review article that synthesizes published research on NPY's involvement in airway immune responses and respiratory disease pathogenesis. The authors examined literature covering NPY receptor biology, airway immunology, and the peptide's roles across multiple respiratory conditions.","limitations":"As a narrative review, this study does not present original experimental data and may be subject to selection bias in the literature covered. The abstract does not detail the specific mechanisms by which NPY affects each disease, and much of the underlying research may come from animal models that don't perfectly translate to human disease."},{"rthcId":"RPEP-08442","title":"Acute salivary antimicrobial peptide secretion response to different exercise intensities and durations.","authors":"Ito, Reita; Uchino, Takamasa; Uchida, Masataka; Fujie, Shumpei; Iemitsu, Keiko; Kojima, Chihiro; Nakamura, Mariko; Shimizu, Kazuhiro; Tanimura, Yuko; Shinohara, Yasushi; Hashimoto, Takeshi; Isaka, Tadao; Iemitsu, Motoyuki","year":2024,"journal":"American journal of physiology. Regulatory, integrative and comparative physiology, 327(6), R616-R622","doi":"10.1152/ajpregu.00132.2024","pmid":"39155711","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08443","title":"Food-induced small bowel obstruction observed in a patient with inappropriate use of semaglutide.","authors":"Itoh, Yoshito; Tani, Misato; Takahashi, Ryo; Yamamoto, Koji","year":2024,"journal":"Diabetology international, 15(4), 850-854","doi":"10.1007/s13340-024-00751-4","pmid":"39469548","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08444","title":"Effectiveness of switching from dipeptidyl peptidase-4 inhibitor to oral glucagon-like peptide-1 receptor agonist in Japanese participants with type 2 diabetes mellitus: Prospective observational study using propensity score matching.","authors":"Iwamoto, Hideyuki; Kimura, Tomohiko; Fushimi, Yoshiro; Iwamoto, Masahiro; Tatsumi, Fuminori; Sanada, Junpei; Iwamoto, Yuichiro; Katakura, Yukino; Shimoda, Masashi; Nakanishi, Shuhei; Mune, Tomoatsu; Kaku, Kohei; Kaneto, Hideaki","year":2024,"journal":"Diabetes, obesity & metabolism, 26(10), 4366-4374","doi":"10.1111/dom.15784","pmid":"39039725","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08445","title":"Tirzepatide, a dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide 1 receptor agonist, exhibits favourable effects on pancreatic β-cells and hepatic steatosis in obese type 2 diabetic db/db mice.","authors":"Iwamoto, Yuichiro; Kimura, Tomohiko; Dan, Kazunori; Iwamoto, Hideyuki; Sanada, Junpei; Fushimi, Yoshiro; Katakura, Yukino; Shimoda, Masashi; Yamasaki, Yuki; Nogami, Yuka; Shirakiya, Yoshiko; Nakanishi, Shuhei; Mune, Tomoatsu; Kaku, Kohei; Kaneto, Hideaki","year":2024,"journal":"Diabetes, obesity & metabolism, 26(12), 5982-5994","doi":"10.1111/dom.15972","pmid":"39344853","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08446","title":"Switching to Tirzepatide 5 mg From Glucagon-Like Peptide-1 Receptor Agonists: Clinical Expectations in the First 12 Weeks of Treatment.","authors":"Jabbour, Serge; Paik, Jim S; Aleppo, Grazia; Sharma, Palash; Gomez Valderas, Elisa; Benneyworth, Brian D","year":2024,"journal":"Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists, 30(8), 701-709","doi":"10.1016/j.eprac.2024.05.005","pmid":"38723893","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In participants switching from stable GLP-1 RA treatment to tirzepatide 5 mg:\n- HbA1c decreased by -0.43% at 12 weeks (p<0.01)\n- Fasting serum glucose decreased by -7.83 mg/dL (p<0.01)\n- Body weight decreased by -2.15 kg (p<0.01)\n- Improvements occurred across all baseline GLP-1 RA subgroups (semaglutide, dulaglutide, liraglutide)\n- 13.2% (20 participants) developed gastrointestinal events\n- 2% (3 participants) discontinued due to adverse events\n- No severe hypoglycemia or deaths\n\nBaseline characteristics: mean age 58.3 years, HbA1c 7.39%, BMI 35.18 kg/m², T2D duration ~12.4 years, 55% female. Most were switching from semaglutide 1.0 mg (55%) or dulaglutide 1.5 mg (42%).","whyItMatters":"As millions of patients are already on GLP-1 drugs, clinicians frequently face the practical question: should patients switch to tirzepatide, and how? This study provides the first prospective data showing that a direct switch to tirzepatide's starting dose provides additional metabolic benefits beyond what GLP-1 monotherapy achieves, with a manageable side effect profile. This directly informs clinical decision-making for the growing population on incretin-based therapies.","specificNumbers":"","methodology":"Prospective, open-label study enrolling adults ≥18 years with T2D (HbA1c 6.5-9.0%, BMI ≥25 kg/m²) on stable GLP-1 RA doses for ≥3 months. Participants were switched directly to tirzepatide 5 mg. Primary endpoint was HbA1c change at 12 weeks. Secondary endpoints included fasting glucose, body weight, and continuous glucose monitoring metrics. Safety was assessed throughout.","limitations":"This is an open-label study without a comparator group of patients continuing their GLP-1 RA, so it's impossible to separate the effect of switching to tirzepatide from natural disease progression or placebo effects. The 12-week follow-up is relatively short. Most participants switched from moderate GLP-1 RA doses — results may differ for those on maximum doses. The study was industry-sponsored (Eli Lilly, which manufactures tirzepatide)."},{"rthcId":"RPEP-08447","title":"The Adipokinetic Hormone (AKH) and the Adipokinetic Hormone/Corazonin-Related Peptide (ACP) Signalling Systems of the Yellow Fever Mosquito Aedes aegypti: Chemical Models of Binding.","authors":"Jackson, Graham E; Sani, Marc-Antoine; Marco, Heather G; Separovic, Frances; Gäde, Gerd","year":2024,"journal":"Biomolecules, 14(3)","doi":"10.3390/biom14030313","pmid":"38540733","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The researchers determined the 3D solution structures of both AKH and ACP hormones using NMR spectroscopy, then built atomic-scale models of their G protein-coupled receptors using homology modeling. Blind docking simulations identified how each hormone binds to its specific receptor.\n\nThe models explained why these two systems are exclusive — each receptor only binds its own hormone, not the other. Validation against existing experimental data showed largely acceptable agreement, confirming the models are usable for future drug discovery. The study noted that distinguishing true agonists from antagonists may require additional experimental testing.","whyItMatters":"Aedes aegypti mosquitoes transmit yellow fever, dengue, Zika, and other devastating diseases. Understanding mosquito-specific peptide signaling at the molecular level could enable the development of insecticides that precisely target mosquito biology while leaving human peptide systems unaffected, since the insect and vertebrate systems have diverged significantly.","specificNumbers":"","methodology":"The study combined nuclear magnetic resonance (NMR) spectroscopy to determine peptide structures in solution, homology modeling to construct 3D receptor structures, and blind docking simulations to predict binding sites. Results were validated by comparing computational predictions to published experimental data from the literature.","limitations":"This is entirely a computational study — the receptor models are predictions based on homology modeling, not experimentally determined crystal structures. The authors acknowledge that distinguishing antagonists from agonists may require additional experimental testing. Only two signaling systems from one mosquito species were examined."},{"rthcId":"RPEP-08448","title":"The Road towards Triple Agonists: Glucagon-Like Peptide 1, Glucose-Dependent Insulinotropic Polypeptide and Glucagon Receptor - An Update.","authors":"Jakubowska, Agnieszka; Roux, Carel W le; Viljoen, Adie","year":2024,"journal":"Endocrinology and metabolism (Seoul, Korea), 39(1), 12-22","doi":"10.3803/EnM.2024.1942","pmid":"38356208","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08449","title":"Peptide-Based Therapeutics in Cancer Therapy.","authors":"Jalil, Abduladheem Turki; Abdulhadi, Mohanad Ali; Al-Ameer, Lubna R; Taher, Waam Mohammed; Abdulameer, Sada Jasim; Abosaooda, Munther; Fadhil, Ali A","year":2024,"journal":"Molecular biotechnology, 66(10), 2679-2696","doi":"10.1007/s12033-023-00873-1","pmid":"37768503","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08450","title":"Clinical Consequences of Delayed Gastric Emptying With GLP-1 Receptor Agonists and Tirzepatide.","authors":"Jalleh, Ryan J; Plummer, Mark P; Marathe, Chinmay S; Umapathysivam, Mahesh M; Quast, Daniel R; Rayner, Christopher K; Jones, Karen L; Wu, Tongzhi; Horowitz, Michael; Nauck, Michael A","year":2024,"journal":"The Journal of clinical endocrinology and metabolism, 110(1), 1-15","doi":"10.1210/clinem/dgae719","pmid":"39418085","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08451","title":"Gastrointestinal effects of GLP-1 receptor agonists: mechanisms, management, and future directions.","authors":"Jalleh, Ryan J; Rayner, Chris K; Hausken, Trygve; Jones, Karen L; Camilleri, Michael; Horowitz, Michael","year":2024,"journal":"The lancet. Gastroenterology & hepatology, 9(10), 957-964","doi":"10.1016/S2468-1253(24)00188-2","pmid":"39096914","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08452","title":"Physiology and Pharmacology of Effects of GLP-1-based Therapies on Gastric, Biliary and Intestinal Motility.","authors":"Jalleh, Ryan J; Marathe, Chinmay S; Rayner, Christopher K; Jones, Karen L; Umapathysivam, Mahesh M; Wu, Tongzhi; Quast, Daniel R; Plummer, Mark P; Nauck, Michael A; Horowitz, Michael","year":2024,"journal":"Endocrinology, 166(1)","doi":"10.1210/endocr/bqae155","pmid":"39568409","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08453","title":"Semaglutide and Tirzepatide for the Management of Weight Recurrence After Sleeve Gastrectomy: A Retrospective Cohort Study.","authors":"Jamal, Mohammad; Alhashemi, Mohsen; Dsouza, Carol; Al-Hassani, Sara; Qasem, Wafa; Almazeedi, Sulaiman; Al-Sabah, Salman","year":2024,"journal":"Obesity surgery, 34(4), 1324-1332","doi":"10.1007/s11695-024-07137-0","pmid":"38430320","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08454","title":"Fasting GLP-1 Levels and Albuminuria Are Negatively Associated in Patients with Type 2 Diabetes Mellitus.","authors":"Jang, Cheol-Won; Yu, Tae Yang; Jeong, Jin Woo; Ha, Se Eun; Singh, Rajan; Lee, Moon Young; Ro, Seungil","year":2024,"journal":"Journal of personalized medicine, 14(3)","doi":"10.3390/jpm14030280","pmid":"38541022","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08455","title":"Potential Use of GLP-1 and GIP/GLP-1 Receptor Agonists for Respiratory Disorders: Where Are We at?","authors":"Janić, Miodrag; Škrgat, Sabina; Harlander, Matevž; Lunder, Mojca; Janež, Andrej; Pantea Stoian, Anca; El-Tanani, Mohamed; Maggio, Viviana; Rizzo, Manfredi","year":2024,"journal":"Medicina (Kaunas, Lithuania), 60(12)","doi":"10.3390/medicina60122030","pmid":"39768911","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08456","title":"Does Incretin Agonism Have Sustainable Efficacy?","authors":"Janket, Sok-Ja; Chatanaka, Miyo K; Sohaei, Dorsa; Tamimi, Faleh; Meurman, Jukka H; Diamandis, Eleftherios P","year":2024,"journal":"Cells, 13(22)","doi":"10.3390/cells13221842","pmid":"39594592","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"While GLP-1 and GIP receptor agonists have shown unprecedented benefits — blood sugar control, weight loss, reduced cardiovascular and renal risks, and even diabetes prevention from prediabetes — the review raises serious questions about long-term sustainability. Chronic stimulation of pancreatic β-cells may lead to receptor downregulation and β-cell exhaustion, potentially causing β-cell failure over time. The longest randomized trial data available is only 3 years.\n\nThe review also discusses emerging approaches including amylin (which suppresses appetite but can self-aggregate and cause cytotoxicity) and triple agonists combining GLP-1, GIP, and glucagon activity.","whyItMatters":"Millions of people are now using GLP-1 and GIP peptide drugs for diabetes and obesity, with these medications being hailed as transformative. This review asks the critical question that patients and doctors need answered: will these benefits last? The possibility of β-cell exhaustion from chronic peptide receptor stimulation, combined with concerns about manipulating hunger signaling long-term, suggests the sustainability of incretin therapy is genuinely uncertain.","specificNumbers":"3 years = longest RCT duration · GLP-1 + GIP = dual incretin targets · Triple agonists in development (GLP-1 + GIP + glucagon) · Benefits shown on top of metformin or insulin","methodology":"This was a narrative review synthesizing evidence from randomized clinical trials and mechanistic studies on incretin hormones (GLP-1, GIP), amylin, and glucagon. The authors evaluated current efficacy data alongside theoretical and mechanistic concerns about long-term sustainability.","limitations":"As a narrative review, it does not include systematic search methodology or meta-analysis. The sustainability concerns raised are largely theoretical — there is no clinical evidence yet showing β-cell exhaustion from incretin agonists in humans. The 3-year follow-up limitation is real, but the alarmist framing of potential risks is speculative at this stage."},{"rthcId":"RPEP-08457","title":"Anti-calcitonin Gene-Related Peptide Monoclonal Antibodies in Migraine: Focus on Clinical Pharmacokinetics.","authors":"Janković, Slobodan M; Janković, Snežana V","year":2024,"journal":"European journal of drug metabolism and pharmacokinetics, 49(3), 277-293","doi":"10.1007/s13318-024-00885-5","pmid":"38461486","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08458","title":"Anti-Calcitonin Gene-Related Peptide Monoclonal Antibodies in Migraine: Focus on Drug Interactions.","authors":"Janković, Slobodan M; Janković, Snežana V","year":2024,"journal":"European journal of drug metabolism and pharmacokinetics, 49(3), 263-275","doi":"10.1007/s13318-024-00887-3","pmid":"38457093","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08459","title":"Targeting the PAC1 receptor mitigates degradation of myelin and synaptic markers and diminishes locomotor deficits in the cuprizone demyelination model.","authors":"Jansen, Margo I; Mahmood, Yasir; Lee, Jordan; Broome, Sarah Thomas; Waschek, James A; Castorina, Alessandro","year":2024,"journal":"Journal of neurochemistry, 168(9), 3250-3267","doi":"10.1111/jnc.16199","pmid":"39115025","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08460","title":"Anti-Biofilm and Anti-Inflammatory Properties of the Truncated Analogs of the Scorpion Venom-Derived Peptide IsCT against Pseudomonas aeruginosa.","authors":"Jantaruk, Pornpimon; Teerapo, Kittitat; Charoenwutthikun, Supattra; Roytrakul, Sittiruk; Kunthalert, Duangkamol","year":2024,"journal":"Antibiotics (Basel, Switzerland), 13(8)","doi":"10.3390/antibiotics13080775","pmid":"39200075","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08461","title":"Average steps per day as marker of treatment response with anti-CGRP mAbs in adults with chronic migraine: a pilot study.","authors":"Jantzen, Frederik Thal; Chaudhry, Basit Ali; Younis, Samaira; Nørgaard, Ina; Cullum, Christopher Kjaer; Do, Thien Phu; Beier, Dagmar; Amin, Faisal Mohammad","year":2024,"journal":"Scientific reports, 14(1), 18068","doi":"10.1038/s41598-024-68915-5","pmid":"39103416","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 22 chronic migraine patients who responded to anti-CGRP monoclonal antibody treatment, median daily steps increased significantly from 4,421 to 5,241 (p=0.039) — an 18.5% increase. The increase in daily steps positively correlated with treatment response measured by reduction in monthly migraine days (p=0.013), suggesting that step count could serve as an objective, passively collected marker of treatment effectiveness.","whyItMatters":"Monitoring migraine treatment response typically relies on patient-reported headache diaries, which are subjective and burdensome. Step count data from smartphones and wearables is automatic and objective. If validated in larger studies, daily step count could become a simple, real-time way for clinicians to track how well anti-CGRP peptide therapies are working — making it easier to identify responders early and adjust treatment.","specificNumbers":"","methodology":"Pilot study enrolling 22 adults with chronic migraine who were classified as responders to anti-CGRP monoclonal antibody treatment. Average daily steps were compared between the 3 months before and 3 months after treatment initiation using automatically recorded step count data. Correlation between step changes and changes in monthly migraine days was assessed.","limitations":"Very small sample size (n=22) with predominantly female participants (20/22). Only treatment responders were included, so the findings don't address whether step count can distinguish responders from non-responders prospectively. Step count data may be influenced by seasonal changes, lifestyle factors, or device-wearing habits. The 3-month comparison window may not capture longer-term activity patterns."},{"rthcId":"RPEP-08462","title":"CROATIAN GUIDELINES FOR SPECIFIC PREVENTIVE TREATMENT OF MIGRAINE WITH MONOCLONAL ANTIBODIES TARGETING CALCITONIN GENE-RELATED PEPTIDE (CGRP) (EPTINEZUMAB, FREMANEZUMAB, AND GALCANEZUMAB) OR THE CGRP RECEPTOR (ERENUMAB).","authors":"Jančuljak, Davor; Petravić, Damir; Mahović Lakušić, Darija; Lovrenčić-Huzjan, Arijana; Bačić Baronica, Koraljka; Bosnar Puretić, Marijana; Hucika, Zlatko; Titlić, Marina; Popović, Zvonimir; Tomić, Zoran; Stojić, Maristela; Bašić Kes, Vanja","year":2024,"journal":"Acta clinica Croatica, 63(2), 436-450","doi":"10.20471/acc.2024.63.02.22","pmid":"40104234","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08463","title":"GLP-1-based therapies for the treatment of resistant hypertension in individuals with overweight or obesity: a review.","authors":"Jarade, Candace; Zolotarova, Tetiana; Moiz, Areesha; Eisenberg, Mark J","year":2024,"journal":"EClinicalMedicine, 75, 102789","doi":"10.1016/j.eclinm.2024.102789","pmid":"39246720","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08464","title":"Prediction, screening and characterization of novel bioactive tetrapeptide matrikines for skin rejuvenation.","authors":"Jariwala, Nathan; Ozols, Matiss; Eckersley, Alexander; Mambwe, Bezaleel; Watson, Rachel E B; Zeef, Leo; Gilmore, Andrew; Debelle, Laurent; Bell, Mike; Bradley, Eleanor J; Doush, Yegor; Keenan, Amy; Courage, Carole; Leroux, Richard; Peschard, Olivier; Mondon, Philippe; Ringenbach, Caroline; Bernard, Laure; Pitois, Aurelien; Sherratt, Michael J","year":2024,"journal":"The British journal of dermatology, 191(1), 92-106","doi":"10.1093/bjd/ljae061","pmid":"38375775","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"From computational protease cleavage prediction, researchers identified candidate tetrapeptides and tested them on cultured human dermal fibroblasts. All applied peptides triggered cellular responses, but the effects were highly sequence-dependent.\n\nTwo peptides — GPKG (glycine-proline-lysine-glycine) and LSVD (leucine-serine-valine-aspartate) — were selected for further characterization based on bioactivity, low toxicity, and protein source. In vitro, they enhanced transcription of matrix organization and cell proliferation genes. In a short-term patch test, they promoted processes associated with epithelial and dermal maintenance and remodeling. In a longer-term split-face clinical study, prolonged use of a formulation containing both peptides led to significantly improved measures of crow's feet and skin firmness in a mixed population.","whyItMatters":"Peptide-based skincare is a booming market, but most products rely on peptides discovered by trial and error. This study introduces a rational, hypothesis-driven approach to peptide discovery — predicting which naturally occurring skin fragments have biological activity, then validating them through rigorous testing up to human clinical trials. The full pipeline from computation to clinical proof published in a top dermatology journal sets a new standard for cosmetic peptide research.","specificNumbers":"","methodology":"A full discovery-to-clinical pipeline was used: (1) In silico protease cleavage site prediction to identify putative matrikine peptides from skin matrix proteins. (2) In vitro screening using proteomic and transcriptomic analysis in cultured human dermal fibroblasts. (3) Short-term in vivo patch test to assess biological activity on human skin. (4) Longer-term split-face clinical study to evaluate cosmetic efficacy of a formulation containing the lead peptide combination (GPKG + LSVD). Published in the British Journal of Dermatology.","limitations":"The abstract does not specify the clinical study sample size, duration, or statistical details beyond 'significantly improved.' The split-face design, while robust for cosmetic studies, does not account for systemic effects. The peptides were tested as a combination formulation, making it unclear which peptide contributed more to the clinical results. Long-term safety and efficacy beyond the study period are unknown. The formulation vehicle may contribute to the observed effects."},{"rthcId":"RPEP-08465","title":"RGD peptide in cancer targeting: Benefits, challenges, solutions, and possible integrin-RGD interactions.","authors":"Javid, Hossein; Oryani, Mahsa Akbari; Rezagholinejad, Nastaran; Esparham, Ali; Tajaldini, Mahboubeh; Karimi-Shahri, Mehdi","year":2024,"journal":"Cancer medicine, 13(2), e6800","doi":"10.1002/cam4.6800","pmid":"38349028","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08466","title":"In Vitro Multi-Bioactive Potential of Enzymatic Hydrolysis of a Non-Toxic Jatropha curcas Cake Protein Isolate.","authors":"Javier, Olloqui Enrique; Alejandro, González-Rodríguez Maurilio; Elizabeth, Contreras-López; Guadalupe, Pérez-Flores Jesús; Emmanuel, Pérez-Escalante; Carlos, Moreno-Seceña Juan; Daniel, Martínez-Carrera","year":2024,"journal":"Molecules (Basel, Switzerland), 29(13)","doi":"10.3390/molecules29133088","pmid":"38999040","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08467","title":"Neuropeptide Network of Polycystic Ovary Syndrome - A Review.","authors":"Jayamurali, Dheepthi; Ravishankar, Nivetha; Manoharan, Nivedita; Parasuraman, Rajeshwari; Jayashankar, Sri Kameshwaran; Govindarajulu, Sathya Narayanan","year":2024,"journal":"Protein and peptide letters, 31(9), 667-680","doi":"10.2174/0109298665309949240822105900","pmid":"39313871","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08468","title":"Substance P-A neuropeptide regulator of periodontal disease pathogenesis and potential novel therapeutic entity: A narrative review.","authors":"Jayanthi, A; Tiwari, D; Puzhankara, L","year":2024,"journal":"Journal of Indian Society of Periodontology, 28(3), 284-289","doi":"10.4103/jisp.jisp_56_24","pmid":"39742059","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Substance P levels in gingival crevicular fluid are highest in areas with active periodontal disease and bone loss. SP contributes to periodontal pathology through multiple mechanisms: triggering neurogenic inflammation, modulating immune responses, promoting bone resorption, and sustaining pain in vulnerable tissues. SP expression during disease progression may represent a risk factor for systemic inflammatory diseases like chronic arthritis. SP also plays roles in tissue regeneration, suggesting it could be both a therapeutic target and a regenerative tool.","whyItMatters":"Periodontal disease affects nearly half of adults and is increasingly linked to systemic conditions including heart disease, diabetes, and arthritis. Understanding that the neuropeptide substance P drives gum inflammation and bone loss opens new therapeutic avenues beyond traditional mechanical cleaning and antibiotics. NK1 receptor antagonists (substance P blockers) already exist for other conditions and could potentially be repurposed for periodontal management, representing a novel neuropeptide-targeted approach to oral health.","specificNumbers":"","methodology":"Narrative review searching PubMed/MEDLINE and SCOPUS for published articles on substance P's role in inflammation and periodontal disease. Search terms included \"substance p AND periodontal*\" AND \"therapeutics.\" Eligible full-text articles were retrieved and data extracted on SP's role in periodontal health, disease, and therapy.","limitations":"This is a narrative review without systematic methodology or quantitative analysis. Most evidence for substance P's role comes from observational studies measuring SP levels in gum fluid, which cannot establish causation. The therapeutic potential of targeting SP in periodontal disease is speculative — no clinical trials of NK1 antagonists for gum disease have been conducted. The dual role of SP in both inflammation and regeneration makes therapeutic targeting complex."},{"rthcId":"RPEP-08469","title":"Exosomes derived from olive flounders infected with Streptococcus parauberis: Proteomic analysis, immunomodulation, and disease resistance capacity.","authors":"Jayathilaka, E H T Thulshan; Edirisinghe, Shan Lakmal; De Zoysa, Mahanama; Nikapitiya, Chamilani","year":2024,"journal":"Fish & shellfish immunology, 148, 109478","doi":"10.1016/j.fsi.2024.109478","pmid":"38452957","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08470","title":"AT-7687, a novel GIPR peptide antagonist, combined with a GLP-1 agonist, leads to enhanced weight loss and metabolic improvements in cynomolgus monkeys.","authors":"Jensen, Mette H; Sanni, Samra J; Riber, Ditte; Holst, Jens J; Rosenkilde, Mette M; Sparre-Ulrich, Alexander H","year":2024,"journal":"Molecular metabolism, 88, 102006","doi":"10.1016/j.molmet.2024.102006","pmid":"39128651","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08471","title":"Bone Health After Exercise Alone, GLP-1 Receptor Agonist Treatment, or Combination Treatment: A Secondary Analysis of a Randomized Clinical Trial.","authors":"Jensen, Simon Birk Kjær; Sørensen, Victor; Sandsdal, Rasmus Michael; Lehmann, Eva Winning; Lundgren, Julie Rehné; Juhl, Christian Rimer; Janus, Charlotte; Ternhamar, Tummas; Stallknecht, Bente Merete; Holst, Jens Juul; Jørgensen, Niklas Rye; Jensen, Jens-Erik Beck; Madsbad, Sten; Torekov, Signe Sørensen","year":2024,"journal":"JAMA network open, 7(6), e2416775","doi":"10.1001/jamanetworkopen.2024.16775","pmid":"38916894","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08472","title":"IN VITRO ANTICANCER ACTIVITY OF HISTATIN-1 COMBINATION WITH CISPLATIN IN HEAD AND NECK CANCER CELL LINES.","authors":"Jenwanichkul, P; Amornphimoltham, P","year":2024,"journal":"Experimental oncology, 46(2), 101-109","doi":"10.15407/exp-oncology.2024.02.101","pmid":"39396174","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08473","title":"Ghrelin system and GLP-1 as potential treatment targets for alcohol use disorder.","authors":"Jerlhag, Elisabet","year":2024,"journal":"International review of neurobiology, 178, 401-432","doi":"10.1016/bs.irn.2024.07.006","pmid":"39523062","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08474","title":"Evaluating the cytotoxicity mechanism of the cell-penetrating peptide TP10 on Jurkat cells.","authors":"Ji, Kun; Yao, Yufan; Gao, Yuxuan; Huang, Sujie; Ma, Ling; Pan, Qing; Wu, Jun; Zhang, Wei; Chen, Hongmei; Zhang, Lei","year":2024,"journal":"Biochimie, 221, 182-192","doi":"10.1016/j.biochi.2023.11.001","pmid":"37922978","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08475","title":"Efficacy and safety of oral semaglutide vs sitagliptin in a predominantly Chinese population with type 2 diabetes uncontrolled with metformin: PIONEER 12, a double-blind, Phase IIIa, randomised trial.","authors":"Ji, Linong; Agesen, Rikke M; Bain, Stephen C; Fu, Fangming; Gabery, Sanaz; Geng, Jianlin; Li, Yiming; Lu, Yibing; Luo, Bifen; Pang, Wuyan; Tao, Yi","year":2024,"journal":"Diabetologia, 67(9), 1800-1816","doi":"10.1007/s00125-024-06133-4","pmid":"38985161","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08476","title":"Impact of baseline characteristics on the efficacy of once-weekly subcutaneous semaglutide among participants with type 2 diabetes: A post hoc analysis of SUSTAIN China.","authors":"Ji, Linong; Lu, Yibing; Shen, Zewei; Hu, Ping; Liu, Wenyan; Zhang, Qiu; Shi, Bimin","year":2024,"journal":"Diabetes, obesity & metabolism, 26(11), 5312-5324","doi":"10.1111/dom.15888","pmid":"39279647","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08477","title":"Glucagon-like peptide-1 receptor agonists in neoplastic diseases.","authors":"Ji, Lisan; He, Xianzhen; Min, Xinwen; Yang, Handong; Wu, Wenwen; Xu, Hao; Chen, Jun; Mei, Aihua","year":2024,"journal":"Frontiers in endocrinology, 15, 1465881","doi":"10.3389/fendo.2024.1465881","pmid":"39371922","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08478","title":"Arboviruses antagonize insect Toll antiviral immune signaling to facilitate the coexistence of viruses with their vectors.","authors":"Jia, Dongsheng; Luo, Guozhong; Guan, Heran; Yu, Tingting; Sun, Xinyan; Du, Yu; Wang, Yiheng; Chen, Hongyan; Wei, Taiyun","year":2024,"journal":"PLoS pathogens, 20(6), e1012318","doi":"10.1371/journal.ppat.1012318","pmid":"38865374","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08479","title":"Oxidative Stress, Ferroptosis Indicators, and Nicorandil Efficacy in STEMI Patients During Percutaneous Coronary Intervention.","authors":"Jia, Shengqi; Tian, Dingyuan; Zhang, Weifeng; Jia, Haiyan; Zhang, Jing; Jia, Xinwei; Li, Yongjun","year":2024,"journal":"Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis, 30, 10760296241296137","doi":"10.1177/10760296241296137","pmid":"39529280","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08480","title":"Neuropeptide Y receptor Y8b (npy8br) regulates feeding and digestion in Japanese medaka (Oryzias latipes) larvae: evidence from gene knockout.","authors":"Jia, Xiaodan; Lu, Ke; Liang, Xufang","year":2024,"journal":"Journal of Zhejiang University. Science. B, 25(7), 605-616","doi":"10.1631/jzus.B2300312","pmid":"39011680","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08481","title":"The mechanism of transcutaneous gastric pacing treatment on gastrointestinal motility recovery and inflammation improvement in early-stage acute pancreatitis patients.","authors":"Jia, Zhenyu; Kong, Lingchao; Lu, Xiaochun; Lu, Jianying; Shen, Yuying; Qiao, Zhenguo; Xia, Tingting","year":2024,"journal":"BMC gastroenterology, 24(1), 407","doi":"10.1186/s12876-024-03498-z","pmid":"39538196","tags":[],"studyType":"rct","evidenceStrength":"moderate","keyFinding":"Transcutaneous gastric pacing (TGP) significantly improved gastrointestinal recovery in early-stage acute pancreatitis patients compared to conventional treatment. The TGP group had shorter time to first bowel movement (p<0.05) and fewer hospital days (p<0.05). Mechanistically, TGP decreased serum vasoactive intestinal peptide (VIP) levels (p<0.05), increased normal gastric slow waves (p<0.05), and reduced the inflammatory marker IL-6 (p<0.05).\n\nAutonomic nervous system testing revealed TGP increased vagal (parasympathetic) activity while decreasing sympathetic activity (both p<0.01), suggesting the treatment works by restoring autonomic balance through vagal stimulation, which in turn normalizes gastrointestinal peptide signaling.","whyItMatters":"Acute pancreatitis frequently disrupts gut motility, prolonging hospitalization and worsening outcomes. Current treatments are largely supportive. This study shows that a non-invasive electrical stimulation device can restore gut function faster, and reveals that the mechanism involves normalization of gastrointestinal peptide hormones — specifically reducing VIP, which inhibits gut motility when elevated. Understanding this peptide-mediated mechanism could lead to better targeted therapies for gut motility disorders.","specificNumbers":"n=65 · Shorter first defecation time (p<0.05) · Fewer hospital days (p<0.05) · VIP decreased (p<0.05) · Normal gastric slow waves increased (p<0.05) · IL-6 decreased (p<0.05) · Vagal activity (HF) increased (p<0.01) · Sympathetic activity (LF) decreased (p<0.01)","methodology":"Sixty-five patients with early-stage acute pancreatitis were randomly assigned to conventional treatment or conventional treatment plus transcutaneous gastric pacing. Researchers measured serum ghrelin and VIP (peptide hormones), electrogastrogram parameters (gastric electrical activity), time to first bowel movement, hospital stay length, IL-6 inflammatory markers, and heart rate variability to assess autonomic nervous system function.","limitations":"The sample size is relatively small (65 patients). The abstract does not report blinding, which could introduce placebo effects — patients in the TGP group knew they were receiving the device. Ghrelin levels were measured but not reported as significantly different, limiting the peptide mechanism story. The study was conducted at a single center, and longer-term outcomes were not assessed."},{"rthcId":"RPEP-08482","title":"A Case of Severe Cholestatic Hepatitis Induced by a Novel Dual Agonist of Glucagon-like Peptide-1 and Glucose-dependent Insulinotropic Polypeptide Receptors.","authors":"Jiang, Junmin; Shi, Meifeng; Wu, Shuduo; Cao, Minling","year":2024,"journal":"Journal of clinical and translational hepatology, 12(11), 949-954","doi":"10.14218/JCTH.2024.00287","pmid":"39544242","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08483","title":"Discovery of a Novel Glucagon-like Peptide-1 (GLP-1) Analogue from Bullfrog and Investigation of Its Potential for Designing GLP-1-Based Multiagonists.","authors":"Jiang, Neng; Su, Di; Chen, De; Huang, Shutong; Tang, Chunli; Jing, Lin; Yang, Caiyan; Zhou, Zhongbo; Yan, Zhiming; Han, Jing","year":2024,"journal":"Journal of medicinal chemistry, 67(1), 180-198","doi":"10.1021/acs.jmedchem.3c01049","pmid":"38117235","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Bullfrog GLP-1 (bGLP-1) showed the highest potency among natural GLP-1 analogues screened from fish and amphibians. Through structure-activity optimization and long-acting modifications, the researchers created analogue 2f, which showed superior effects on food intake, glycemic control, and body weight compared to semaglutide.\n\nUsing the bGLP-1 sequence as a scaffold, they also designed dual GLP-1/glucagon receptor agonist (3o) and triple GLP-1/GIP/glucagon receptor agonist (4b), both of which demonstrated significant therapeutic effects on lipid regulation, glycemic control, and body weight in preclinical testing.","whyItMatters":"Nature remains a powerful source for drug discovery. Finding a GLP-1 analogue from bullfrogs that outperforms semaglutide highlights the potential of natural peptides as starting points for next-generation obesity and diabetes drugs. The ability to use this natural scaffold for designing multi-receptor agonists further demonstrates the versatility of this approach.","specificNumbers":"","methodology":"Researchers screened GLP-1 analogues from fish and amphibians for receptor potency, then selected bullfrog GLP-1 for optimization. They conducted structure-activity relationship studies, made long-acting modifications, and tested candidates in animal models for effects on food intake, blood glucose, and body weight. They also used the bullfrog GLP-1 sequence to engineer dual and triple receptor agonists targeting GLP-1, glucagon, and GIP receptors, evaluating their effects on metabolism and body weight.","limitations":"All testing was conducted in animal models, and preclinical superiority over semaglutide does not guarantee the same advantage in humans. Pharmacokinetics, safety, and long-term effects have not been established. The study does not report on potential immunogenicity of a frog-derived peptide in human applications. Clinical development would require extensive further testing."},{"rthcId":"RPEP-08484","title":"Machine learning application to predict binding affinity between peptide containing non-canonical amino acids and HLA0201.","authors":"Jiang, Shan; Su, Zhaoqian; Bloodworth, Nathaniel; Liu, Yunchao; Martina, Cristina; Harrison, David G; Meiler, Jens","year":2024,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2024.11.19.624425","pmid":"39605664","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08485","title":"Therapeutic Function of Liraglutide for Mitigation of Blast-Induced Hearing Damage: An Initial Investigation in Animal Model of Chinchilla.","authors":"Jiang, Shangyuan; Sanders, Sarah; Welch, Paige; Gan, Rong Z","year":2024,"journal":"Military medicine, 189(Suppl 3), 407-415","doi":"10.1093/milmed/usae142","pmid":"39160824","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08486","title":"Exenatide and Metformin Improve Serum Indices and Intestinal Flora in patients with Type 2 Diabetes Mellitus and Non-Alcoholic Fatty Liver Disease.","authors":"Jiang, Xiaojie; Shi, Tingting; Han, Dan; Chen, Juan","year":2024,"journal":"JPMA. The Journal of the Pakistan Medical Association, 74(1), 138-140","doi":"10.47391/JPMA.8295","pmid":"38219182","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"After 24 weeks, exenatide plus metformin (Group B) was significantly superior to metformin alone (Group A) across all measured outcomes: fasting blood glucose, postprandial glucose, triglycerides, total cholesterol, ALT, and AST were all lower in the combination group (p<0.001 for all).\n\nThe combination also significantly improved intestinal flora: counts of harmful bacteria (E. coli and Enterococcus faecalis) were lower (p<0.05), while beneficial bacteria (Bifidobacteria and Lactobacillus) were higher (p<0.05) in the combination group. This suggests exenatide and metformin have synergistic effects on metabolic, hepatic, and microbiome parameters.","whyItMatters":"Type 2 diabetes and fatty liver disease frequently coexist, and treating both simultaneously is a clinical priority. This study shows that adding a GLP-1 peptide drug (exenatide) to standard metformin therapy provides comprehensive improvement — not just better blood sugar, but also liver protection and a healthier gut microbiome. The gut flora changes suggest a novel mechanism through which GLP-1 drugs may benefit liver health.","specificNumbers":"","methodology":"This was a randomized controlled trial of 128 type 2 diabetes patients with non-alcoholic fatty liver disease, diagnosed between January 2019 and January 2022. Patients were randomly assigned to metformin alone (n=64) or exenatide injection plus metformin (n=64) for 24 weeks. Outcomes included fasting and postprandial blood glucose, triglycerides, total cholesterol, liver enzymes (ALT, AST), and stool samples for intestinal flora analysis.","limitations":"The study was open-label (not blinded), which could introduce bias in subjective assessments. It was conducted at a single center with a relatively homogeneous population. The abstract doesn't report specific numerical values for outcomes, making it hard to assess the magnitude of differences. The gut flora analysis appears limited to specific cultured species rather than comprehensive metagenomic sequencing. No liver imaging endpoints were reported."},{"rthcId":"RPEP-08487","title":"Effectiveness and safety of glucagon-like peptide 1 receptor agonists in patients with type 2 diabetes: evidence from a retrospective real-world study.","authors":"Jiang, Yan; Bai, Han-Sheng; Liu, Guo-Xin; Wang, Shi-Yi; Yin, Li; Hou, Zhao-Ting; Zhao, Chen-Yang; Fan, Guang-Jun","year":2024,"journal":"Frontiers in endocrinology, 15, 1347684","doi":"10.3389/fendo.2024.1347684","pmid":"38524632","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08488","title":"Network meta-analysis of the risk of dyspepsia and anorexia in patients with type 2 diabetes mellitus induced by glucagon-like peptide 1 receptor agonist hypoglycemic drugs.","authors":"Jiao, B-L; Zhao, J; Wang, B; Liu, B-Y; Wu, T","year":2024,"journal":"European review for medical and pharmacological sciences, 28(8), 3073-3084","doi":"10.26355/eurrev_202404_36023","pmid":"38708466","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08489","title":"Intestinal glucagon-like peptide-1: A new player associated with impaired counterregulatory responses to hypoglycaemia in type 1 diabetic mice.","authors":"Jin, Fang-Xin; Wang, Yan; Li, Min-Ne; Li, Ru-Jiang; Guo, Jun-Tang","year":2024,"journal":"World journal of diabetes, 15(8), 1764-1777","doi":"10.4239/wjd.v15.i8.1764","pmid":"39192849","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08490","title":"Tranilast alleviates skin inflammation and fibrosis in rosacea-like mice induced by long-term exposure to LL-37.","authors":"Jin, Hui; Wu, Yiling; Zhang, Chuanxi; Zheng, Ruiping; Xu, Hong; Yang, Jie; Li, Linfeng","year":2024,"journal":"Biochemical and biophysical research communications, 737, 150523","doi":"10.1016/j.bbrc.2024.150523","pmid":"39133985","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08491","title":"Dulaglutide treatment reverses depression-like behavior and hippocampal metabolomic homeostasis in mice exposed to chronic mild stress.","authors":"Jin, Man; Zhang, Shipan; Huang, Boya; Li, Litao; Liang, Hao; Ni, Aihua; Han, Lina; Liang, Peng; Liu, Jing; Shi, Haishui; Lv, Peiyuan","year":2024,"journal":"Brain and behavior, 14(3), e3448","doi":"10.1002/brb3.3448","pmid":"38444330","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08492","title":"Structural basis for recognition of 26RFa by the pyroglutamylated RFamide peptide receptor.","authors":"Jin, Sanshan; Guo, Shimeng; Xu, Youwei; Li, Xin; Wu, Canrong; He, Xinheng; Pan, Benxun; Xin, Wenwen; Zhang, Heng; Hu, Wen; Yin, Yuling; Zhang, Tianwei; Wu, Kai; Yuan, Qingning; Xu, H Eric; Xie, Xin; Jiang, Yi","year":2024,"journal":"Cell discovery, 10(1), 58","doi":"10.1038/s41421-024-00670-3","pmid":"38830850","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08493","title":"Brain natriuretic peptide as a predictor of 30-day mortality after return of spontaneous circulation in cardiac arrest patients.","authors":"Jin, Xiaxia; Zheng, Qiaofei; Cheng, Ying; Hu, Lingling; Yang, Wenhui; Li, Jun; Li, Tao","year":2024,"journal":"The American journal of emergency medicine, 86, 87-93","doi":"10.1016/j.ajem.2024.10.010","pmid":"39393148","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08494","title":"Milk-derived extracellular vesicles functionalized with anti-tumour necrosis factor-α nanobody and anti-microbial peptide alleviate ulcerative colitis in mice.","authors":"Jing, Renwei; Zhang, Leijie; Li, Ruibin; Yang, Zhongqiu; Song, Jun; Wang, Qian; Cao, Nan; Han, Gang; Yin, HaiFang","year":2024,"journal":"Journal of extracellular vesicles, 13(6), e12462","doi":"10.1002/jev2.12462","pmid":"38840457","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The cell-penetrating peptide TAT enabled efficient loading of biologic drugs into milk-derived extracellular vesicles (EVs) and protected them from degradation in the gastrointestinal tract both in vitro and in vivo.\n\nOral delivery of EVs loaded with the anti-TNF-α nanobody VHHm3F (EVVHH) significantly reduced tissue TNF-α levels and alleviated pathology in mice with acute ulcerative colitis, outperforming the nanobody delivered alone. In chronic UC, EVs simultaneously loaded with both VHH and the antimicrobial peptide LL37 (EVLV) improved the intestinal barrier, reduced inflammation, rebalanced the gut microbiota, and relieved UC-induced depression and anxiety. The TAT-mediated loading approach was described as simple and generalizable to other diseases.","whyItMatters":"Current biologic treatments for IBD typically require injection and cannot be taken orally because they are destroyed in the gut. This study demonstrates a practical oral delivery system using naturally occurring milk vesicles that are safe, scalable, and can carry multiple therapeutic agents simultaneously. The combination of anti-inflammatory and antimicrobial peptide payloads addresses both hallmarks of UC — inflammation and dysbiosis — in a single oral formulation.","specificNumbers":"","methodology":"The researchers engineered milk-derived extracellular vesicles by fusing a cell-penetrating peptide (TAT) to cargo proteins to enable loading. They tested protection against gastrointestinal degradation in vitro and in vivo. Acute UC was modeled in mice to test EVVHH, measuring tissue TNF-α and pathology. Chronic UC was modeled to test the dual-loaded EVLV formulation, assessing intestinal barrier function, inflammation, microbiota composition, and behavioral symptoms (depression/anxiety).","limitations":"All experiments were conducted in mice, and the complexity of human UC — including its chronic relapsing nature and heterogeneous presentation — may not be fully captured by murine models. The scalability and consistency of milk-derived EV production for clinical use is not addressed. Long-term safety of repeated oral EV administration is unknown. The behavioral improvements (anxiety/depression) were measured in mouse models with limited translatability to human neuropsychiatric symptoms."},{"rthcId":"RPEP-08495","title":"From Sea to Lab: Angiotensin I-Converting Enzyme Inhibition by Marine Peptides-Mechanisms and Applications.","authors":"Jo, Du-Min; Khan, Fazlurrahman; Park, Seul-Ki; Ko, Seok-Chun; Kim, Kyung Woo; Yang, Dongwoo; Kim, Ji-Yul; Oh, Gun-Woo; Choi, Grace; Lee, Dae-Sung; Kim, Young-Mog","year":2024,"journal":"Marine drugs, 22(10)","doi":"10.3390/md22100449","pmid":"39452857","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08496","title":"Integrating Multisector Molecular Characterization into Personalized Peptide Vaccine Design for Patients with Newly Diagnosed Glioblastoma.","authors":"Johanns, Tanner M; Garfinkle, Elizabeth A R; Miller, Katherine E; Livingstone, Alexandra J; Roberts, Kaleigh F; Rao Venkata, Lakshmi P; Dowling, Joshua L; Chicoine, Michael R; Dacey, Ralph G; Zipfel, Gregory J; Kim, Albert H; Mardis, Elaine R; Dunn, Gavin P","year":2024,"journal":"Clinical cancer research : an official journal of the American Association for Cancer Research, 30(13), 2729-2742","doi":"10.1158/1078-0432.CCR-23-3077","pmid":"38639919","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08497","title":"Medication adherence to sodium-glucose cotransporter-2 inhibitors versus glucagon-like peptide-1 receptor agonists: A meta-analysis.","authors":"Johnson, Conner E; Sussman, Whitney B; Weeda, Erin R","year":2024,"journal":"Diabetes, obesity & metabolism, 26(10), 4544-4550","doi":"10.1111/dom.15809","pmid":"39044308","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08498","title":"Molecular Modeling of Self-Assembling Peptides.","authors":"Jones, Stephen J; Perez, Alberto","year":2024,"journal":"ACS applied bio materials, 7(2), 543-552","doi":"10.1021/acsabm.2c00921","pmid":"36795608","tags":[],"studyType":"computational","evidenceStrength":"low-moderate","keyFinding":"The researchers tested whether current computational tools can accurately predict how short peptides self-assemble into 3D structures like hydrogels. Using a technique called MELD (Modeling Employing Limited Data) combined with molecular dynamics simulations, they were able to drive self-assembly predictions when standard simulations failed.\n\nCritically, they found that current machine learning algorithms — including the breakthrough protein structure prediction tools — are not yet suited for predicting the assembly of short peptides. This gap means computational design of peptide biomaterials still requires specialized physical modeling approaches rather than off-the-shelf AI tools.","whyItMatters":"Self-assembling peptides are becoming important biomaterials for drug delivery, tissue engineering, and wound healing. Being able to computationally predict how peptides will assemble could dramatically speed up the design of new biomaterials — reducing the expensive trial-and-error of laboratory experiments. This study maps out what computational tools can and can't do right now, providing a roadmap for the field.","specificNumbers":"~40% of protein-protein interactions mediated by peptide epitopes · Short peptides (2-3 amino acids) previously limited atomistic studies · MELD approach used when conventional MD failed · ML algorithms found insufficient for short peptide assembly","methodology":"The researchers used molecular dynamics (MD) simulations and the MELD approach to model peptide self-assembly at the atomic level. MELD incorporates limited experimental data to guide simulations when conventional methods stall. They also benchmarked current machine learning protein structure prediction algorithms against the peptide self-assembly problem to assess their suitability.","limitations":"Physical model inaccuracies and sampling inefficiency remain significant challenges. The MELD approach requires some experimental data to guide predictions, so it's not fully predictive from sequence alone. The finding that ML algorithms don't work for short peptides means the field still lacks a fast, general-purpose computational tool for this problem."},{"rthcId":"RPEP-08499","title":"Carcinoid heart findings in vasoactive intestinal peptide-secreting tumour.","authors":"Joshi, Mugdha; Aldea, Daniel; Ngo, Peter; Shah, Sonia","year":2024,"journal":"BMJ case reports, 17(11)","doi":"10.1136/bcr-2024-262229","pmid":"39510606","tags":[],"studyType":"case-report","evidenceStrength":"low","keyFinding":"A patient with previously undiagnosed VIPoma was found to have tricuspid regurgitation and stenosis on echocardiography — cardiac valve changes typically associated with classical carcinoid syndrome but not historically seen with VIP-secreting tumors. The echocardiographic finding of carcinoid heart disease prompted the workup that ultimately led to the VIPoma diagnosis.\n\nThis is notable because VIPomas have an incidence of only 0.05%–2% of neuroendocrine tumors, and cardiac valve involvement has not been a recognized feature of these tumors. The case suggests that the spectrum of neuroendocrine tumors capable of causing carcinoid heart disease may be wider than previously understood.","whyItMatters":"This case challenges the assumption that only serotonin-secreting carcinoid tumors cause heart valve damage. If VIPomas can also produce carcinoid heart changes, clinicians may need to broaden their diagnostic thinking when they encounter unexplained tricuspid valve disease — potentially catching rare neuroendocrine tumors earlier.","specificNumbers":"VIPoma incidence: 0.05%–2% of neuroendocrine tumors","methodology":"Single patient case report published in BMJ Case Reports. The authors describe a patient whose echocardiogram revealed tricuspid regurgitation and stenosis, which prompted further investigation and ultimately led to the diagnosis of a VIP-secreting tumor.","limitations":"As a single case report, this cannot establish a causal relationship between VIPoma and carcinoid heart disease. It is unclear whether the cardiac findings were directly caused by VIP secretion or by other co-secreted substances. No mechanism is proposed for how VIP might cause valvular changes."},{"rthcId":"RPEP-08500","title":"Unlocking the potential of glucagon-like peptide-1 receptor agonists in revolutionizing type 2 diabetes management: a comprehensive review.","authors":"Joshi, Nandan; Baloch, Kanwal Mir; Rukh, Shah; Khan, Abdul Moiz; Muskan, Fnu; Kumari, Verkha; Khan, Hasher; Zeeshan, Mohd; Azam, Ghufran; Khalid, Saif; Anwar, Insa Binte; Ahmed, Iqra Furqan; Nishat, Syeed Mahmud; Gandhi, Fenil","year":2024,"journal":"Annals of medicine and surgery (2012), 86(12), 7255-7264","doi":"10.1097/MS9.0000000000002712","pmid":"39649934","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08501","title":"Recent advances in liposomes and peptide-based therapeutics for glioblastoma treatment.","authors":"Jourdain, M-A; Eyer, J","year":2024,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 376, 732-752","doi":"10.1016/j.jconrel.2024.10.037","pmid":"39437968","tags":["peptide-delivery","tumor-homing-peptides"],"studyType":"Review","evidenceStrength":"early-stage","keyFinding":"Peptides are being used to solve two of glioblastoma's biggest treatment challenges: getting drugs across the blood-brain barrier (BBB) and targeting them specifically to tumor cells. Tumor-homing peptides can be attached to liposomes (nano-sized drug carriers) to create guided delivery systems that cross the BBB, recognize receptors overexpressed on glioblastoma cells, and penetrate deep into the tumor.\n\nPreclinical studies show these peptide-functionalized liposomes increase drug accumulation in tumors and produce strong antitumor effects. However, major obstacles remain: manufacturing is difficult, characterizing the nanosystems is complex, and antibody-based approaches are competitive alternatives.","whyItMatters":"Glioblastoma is the most lethal brain cancer, with a median survival of about 15 months. The BBB blocks most chemotherapy drugs from reaching the tumor, and even drugs that cross it often don't penetrate deeply into the tumor mass. Peptide-guided liposomes offer a potentially elegant solution: targeted, deep-penetrating drug delivery that could fundamentally change treatment outcomes for this devastating cancer.","specificNumbers":"Review covering GBM-homing peptides, BBB-crossing peptides, peptide-functionalized liposomes, and preclinical in vitro/in vivo results · multiple promising nanosystems described","methodology":"Comprehensive review of the literature on peptide-directed liposomal delivery systems for glioblastoma. The authors describe internalization mechanisms of specific glioblastoma-homing and BBB-penetrating peptides, review preclinical studies of liposomes functionalized with these peptides, and assess the current state and challenges of translating these approaches to clinical use.","limitations":"All evidence is preclinical — no peptide-functionalized liposome systems have reached clinical trials for glioblastoma. Manufacturing complexity and reproducibility are major unsolved challenges. The review acknowledges that antibody-based targeting approaches are more clinically advanced competitors. Animal models of glioblastoma have limited predictive value for human outcomes."},{"rthcId":"RPEP-08502","title":"Traditional herbal medicine Oryeongsan for heart failure: A systematic review and meta-analysis.","authors":"Jung, Da Hae; Lee, Han-Gyul; Kwon, Seungwon; Ha, Won Jung; Cho, Seung-Yeon; Jung, Woo-Sang; Park, Seong-Uk; Moon, Sang-Kwan; Park, Jung-Mi; Ko, Chang-Nam","year":2024,"journal":"Heliyon, 10(18), e37830","doi":"10.1016/j.heliyon.2024.e37830","pmid":"39315159","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08503","title":"Gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs) - Current literature review of diagnostics and therapy. What has changed in the management?","authors":"Jurkiewicz, Krzysztof; Miciak, Michał; Kaliszewski, Krzysztof","year":2024,"journal":"Polski przeglad chirurgiczny, 96(4), 58-66","doi":"10.5604/01.3001.0054.4169","pmid":"39138986","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08504","title":"The association between alpha-1 antitrypsin and B-type natriuretic peptide blood levels in healthy African Americans.","authors":"Justin Margret, Jeffrey; Jain, Sushil K","year":2024,"journal":"BMC research notes, 17(1), 331","doi":"10.1186/s13104-024-06994-3","pmid":"39511686","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08505","title":"The Aggravating Role of Failing Neuropeptide Networks in the Development of Sporadic Alzheimer's Disease.","authors":"Jászberényi, Miklós; Thurzó, Balázs; Jayakumar, Arumugam R; Schally, Andrew V","year":2024,"journal":"International journal of molecular sciences, 25(23)","doi":"10.3390/ijms252313086","pmid":"39684795","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08506","title":"The Orexin/Hypocretin System, the Peptidergic Regulator of Vigilance, Orchestrates Adaptation to Stress.","authors":"Jászberényi, Miklós; Thurzó, Balázs; Bagosi, Zsolt; Vécsei, László; Tanaka, Masaru","year":2024,"journal":"Biomedicines, 12(2)","doi":"10.3390/biomedicines12020448","pmid":"38398050","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08507","title":"Trigeminal ganglion neurons are directly activated by influx of CSF solutes in a migraine model.","authors":"Kaag Rasmussen, Martin; Møllgård, Kjeld; Bork, Peter A R; Weikop, Pia; Esmail, Tina; Drici, Lylia; Wewer Albrechtsen, Nicolai J; Carlsen, Jonathan Frederik; Huynh, Nguyen P T; Ghitani, Nima; Mann, Matthias; Goldman, Steven A; Mori, Yuki; Chesler, Alexander T; Nedergaard, Maiken","year":2024,"journal":"Science (New York, N.Y.), 385(6704), 80-86","doi":"10.1126/science.adl0544","pmid":"38963846","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08508","title":"Clinical characteristics affecting weight loss in an East Asian population receiving semaglutide: A STEP 6 subgroup analysis.","authors":"Kadowaki, Takashi; Lee, Sang Yeoup; Ogawa, Wataru; Nishida, Tomoyuki; Overvad, Maria; Tobe, Kazuyuki; Yamauchi, Toshimasa; Lim, Soo","year":2024,"journal":"Obesity research & clinical practice, 18(6), 457-464","doi":"10.1016/j.orcp.2025.01.002","pmid":"39824696","tags":["glp-1-receptor-agonists"],"studyType":"rct-subgroup","evidenceStrength":"strong","keyFinding":"In the STEP 6 trial subgroup analysis, semaglutide 2.4 mg produced clinically meaningful weight loss across all demographic subgroups in a Japanese and Korean population, with estimated mean weight changes ranging from -9.40% to -16.42% over 68 weeks. Both semaglutide doses outperformed placebo.\n\nNotably, sex significantly affected the response — the treatment-by-sex interaction was highly significant for both doses (p=0.0008 and p=0.0005). Having type 2 diabetes or dyslipidemia at baseline also significantly modified the response to the higher 2.4 mg dose. Despite these variations, semaglutide worked across all subgroups examined.","whyItMatters":"Most major semaglutide weight loss trials (STEP 1-5) were conducted primarily in Western populations. East Asian populations tend to develop obesity-related diseases at lower BMIs and have different body composition patterns. This analysis confirms semaglutide is effective across East Asian demographic subgroups, supporting its use in these populations while highlighting that sex, diabetes status, and dyslipidemia may influence how much weight individual patients lose.","specificNumbers":"n=401 · 148 female, 253 male · Weight loss: -9.40% to -16.42% (semaglutide 2.4 mg) · 68 weeks · Sex interaction p=0.0005 · T2D interaction p=0.0381 · Dyslipidemia interaction p=0.0181","methodology":"Post-hoc subgroup analysis of the STEP 6 randomized controlled trial. Japanese and Korean adults with overweight or obesity received subcutaneous semaglutide 2.4 mg, semaglutide 1.7 mg, or placebo for 68 weeks. Weight change was analyzed by subgroups including baseline weight, BMI, age, sex, glycemic status, dyslipidemia, and hypertension. Treatment-by-subgroup interactions were tested statistically.","limitations":"This is a post-hoc subgroup analysis, meaning the subgroup comparisons were not the primary study objective and may be underpowered. The study included only Japanese and Korean participants, so results may not generalize to all East Asian populations. With 401 total participants split across three arms and multiple subgroups, some subgroup sizes were relatively small."},{"rthcId":"RPEP-08509","title":"Predicting elevated natriuretic peptide in chest radiography: emerging utilization gap for artificial intelligence.","authors":"Kagawa, Eisuke; Kato, Masaya; Oda, Noboru; Kunita, Eiji; Nagai, Michiaki; Yamane, Aya; Matsui, Shogo; Yoshitomi, Yuki; Shimajiri, Hiroto; Hirokawa, Tatsuya; Ishida, Shunsuke; Kurimoto, Genki; Dote, Keigo","year":2024,"journal":"European heart journal. Imaging methods and practice, 2(1), qyae064","doi":"10.1093/ehjimp/qyae064","pmid":"39403705","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08510","title":"Structure-activity relationships of middle-size cyclic peptides, KRAS inhibitors derived from an mRNA display.","authors":"Kage, Mirai; Hayashi, Ryuji; Matsuo, Atsushi; Tamiya, Minoru; Kuramoto, Shino; Ohara, Kazuhiro; Irie, Machiko; Chiyoda, Aya; Takano, Koji; Ito, Toshiya; Kotake, Tomoya; Takeyama, Ryuuichi; Ishikawa, Shiho; Nomura, Kenichi; Furuichi, Noriyuki; Morita, Yuya; Hashimoto, Satoshi; Kawada, Hatsuo; Nishimura, Yoshikazu; Nii, Keiji; Sase, Hitoshi; Ohta, Atsushi; Kojima, Tetsuo; Iikura, Hitoshi; Tanada, Mikimasa; Shiraishi, Takuya","year":2024,"journal":"Bioorganic & medicinal chemistry, 110, 117830","doi":"10.1016/j.bmc.2024.117830","pmid":"38981216","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08511","title":"Effect of Semaglutide on Regression and Progression of Glycemia in People With Overweight or Obesity but Without Diabetes in the SELECT Trial.","authors":"Kahn, Steven E; Deanfield, John E; Jeppesen, Ole Kleist; Emerson, Scott S; Boesgaard, Trine Welløv; Colhoun, Helen M; Kushner, Robert F; Lingvay, Ildiko; Burguera, Bartolome; Gajos, Grzegorz; Horn, Deborah Bade; Hramiak, Irene M; Jastreboff, Ania M; Kokkinos, Alexander; Maeng, Michael; Matos, Ana Laura S A; Tinahones, Francisco J; Lincoff, A Michael; Ryan, Donna H","year":2024,"journal":"Diabetes care, 47(8), 1350-1359","doi":"10.2337/dc24-0491","pmid":"38907683","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08512","title":"New Daily Persistent Headache in the Pediatric and Adolescent Population: An Updated Review.","authors":"Kalika, Paige; Monteith, Teshamae S","year":2024,"journal":"Life (Basel, Switzerland), 14(6)","doi":"10.3390/life14060724","pmid":"38929707","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08513","title":"Designed Cell-Penetrating Peptide Constructs for Inhibition of Pathogenic Protein Self-Assembly.","authors":"Kalmouni, Mona; Oh, Yujeong; Alata, Wael; Magzoub, Mazin","year":2024,"journal":"Pharmaceutics, 16(11)","doi":"10.3390/pharmaceutics16111443","pmid":"39598566","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08514","title":"Pancreatic Safety of Tirzepatide and Its Effects on Islet Cell Function: A Systematic Review and Meta-Analysis.","authors":"Kamrul-Hasan, A B M; Mondal, Sunetra; Dutta, Deep; Nagendra, Lakshmi; Kabir, Mohammed Ruhul; Pappachan, Joseph M","year":2024,"journal":"Obesity science & practice, 10(6), e70032","doi":"10.1002/osp4.70032","pmid":"39720158","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08515","title":"Mucosal Penetrative Polymeric Micelle Formulations for Insulin Delivery to the Respiratory Tract.","authors":"Kang, Ji-Hyun; Jeong, Jin-Hyuk; Kwon, Yong-Bin; Kim, Young-Jin; Shin, Dae Hwan; Park, Yun-Sang; Hyun, Soonsil; Kim, Dong-Wook; Park, Chun-Woong","year":2024,"journal":"International journal of nanomedicine, 19, 9195-9211","doi":"10.2147/IJN.S474287","pmid":"39267725","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08516","title":"Curbing the Obesity Epidemic: Should GLP-1 Receptor Agonists Be the Standard of Care for Obesity?","authors":"Kaplan, Jennifer M; Zaman, Adnin; Abushamat, Layla A","year":2024,"journal":"Current cardiology reports, 26(9), 1011-1019","doi":"10.1007/s11886-024-02097-4","pmid":"39031282","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08517","title":"Glucagon-Like Peptide 1 Receptor Agonists in Patients With Inflammatory Arthritis or Psoriasis: A Scoping Review.","authors":"Karacabeyli, Derin; Lacaille, Diane","year":2024,"journal":"Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases, 30(1), 26-31","doi":"10.1097/RHU.0000000000001949","pmid":"36870080","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08518","title":"Mortality and major adverse cardiovascular events after glucagon-like peptide-1 receptor agonist initiation in patients with immune-mediated inflammatory diseases and type 2 diabetes: A population-based study.","authors":"Karacabeyli, Derin; Lacaille, Diane; Lu, Na; McCormick, Natalie; Xie, Hui; Choi, Hyon K; Aviña-Zubieta, J Antonio","year":2024,"journal":"PloS one, 19(8), e0308533","doi":"10.1371/journal.pone.0308533","pmid":"39116084","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 10,855 adults with autoimmune inflammatory diseases and type 2 diabetes, initiating GLP-1 receptor agonists was associated with 52% lower all-cause mortality (HR 0.48, 95% CI 0.31-0.75) and 34% lower major adverse cardiovascular events (HR 0.66, 95% CI 0.50-0.88) compared to DPP-4 inhibitors. This translated to 9.4 fewer deaths and 10.5 fewer cardiovascular events per 1,000 person-years. The benefit was similar in matched adults without autoimmune diseases.","whyItMatters":"Patients with autoimmune inflammatory diseases (rheumatoid arthritis, IBD, psoriasis, etc.) have elevated cardiovascular risk. This is the first large population study to show that GLP-1 peptide drugs provide substantial mortality and cardiovascular benefits specifically in this high-risk autoimmune population — potentially due to both metabolic and anti-inflammatory effects of GLP-1 receptor agonists.","specificNumbers":"n=10,855 · HR mortality 0.48 (52% reduction) · HR MACE 0.66 (34% reduction) · RD -9.4 deaths/1000 PY · RD -10.5 MACE/1000 PY · 2010-2021 · 5 autoimmune diseases","methodology":"Population-based cohort study using administrative health data from British Columbia, Canada (2010-2021). Patients with an autoimmune inflammatory disease (RA, psoriatic disease, ankylosing spondylitis, IBD, or systemic autoimmune rheumatic disease) and type 2 diabetes who newly started GLP-1 RAs or DPP-4 inhibitors were identified via ICD codes. Propensity score overlap weighting and Cox regression were used. Analysis was repeated in matched adults without autoimmune diseases.","limitations":"Observational study — cannot prove causation despite propensity score weighting. Administrative data may have coding inaccuracies. Specific GLP-1 RA drugs and doses not differentiated. Healthy user bias possible (healthier patients may be preferentially prescribed GLP-1 RAs). Relatively short median follow-up not specified in abstract. No data on weight changes, HbA1c, or inflammatory markers."},{"rthcId":"RPEP-08519","title":"Subcutaneously administered tirzepatide vs semaglutide for adults with type 2 diabetes: a systematic review and network meta-analysis of randomised controlled trials.","authors":"Karagiannis, Thomas; Malandris, Konstantinos; Avgerinos, Ioannis; Stamati, Athina; Kakotrichi, Panagiota; Liakos, Aris; Vasilakou, Despoina; Kakaletsis, Nikolaos; Tsapas, Apostolos; Bekiari, Eleni","year":2024,"journal":"Diabetologia, 67(7), 1206-1222","doi":"10.1007/s00125-024-06144-1","pmid":"38613667","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08520","title":"Regulation of Neuropeptide Y Receptor Gene Expression and Hormone Level in Obese Male Rats Receiving 6-Gingerol and L-Arginine Supplementation.","authors":"Karbasian, M; Panahi, N; Badalzadeh, R; Shirazi-Beheshtiha, S H; Shahbazzade, D","year":2024,"journal":"Archives of Razi Institute, 79(1), 180-188","doi":"10.32592/ARI.2024.79.1.180","pmid":"39192952","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08521","title":"Intervening in the Premonitory Phase to Prevent Migraine: Prospects for Pharmacotherapy.","authors":"Karsan, Nazia; Goadsby, Peter J","year":2024,"journal":"CNS drugs, 38(7), 533-546","doi":"10.1007/s40263-024-01091-2","pmid":"38822165","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08522","title":"Pituitary cyclase-activating polypeptide targeted treatments for the treatment of primary headache disorders.","authors":"Karsan, Nazia; Edvinsson, Lars; Vecsei, Laszlo; Goadsby, Peter J","year":2024,"journal":"Annals of clinical and translational neurology, 11(7), 1654-1668","doi":"10.1002/acn3.52119","pmid":"38887982","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08523","title":"Exploring a Solvent Dependent Strategy to Control Self-Assembling Behavior and Cellular Interaction in Laminin-Mimetic Short Peptide based Supramolecular Hydrogels.","authors":"Kashyap, Shambhavi; Pal, Vijay Kumar; Mohanty, Sweta; Roy, Sangita","year":2024,"journal":"Chembiochem : a European journal of chemical biology, 25(8), e202300835","doi":"10.1002/cbic.202300835","pmid":"38390634","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08524","title":"The State-of-the-Art Mechanisms and Antitumor Effects of Somatostatin in Colorectal Cancer: A Review.","authors":"Kasprzak, Aldona; Geltz, Agnieszka","year":2024,"journal":"Biomedicines, 12(3)","doi":"10.3390/biomedicines12030578","pmid":"38540191","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08525","title":"Efficacy, adherence and persistence of various glucagon-like peptide-1 agonists: nationwide real-life data.","authors":"Kassem, Sameer; Khalaila, Buthaina; Stein, Nili; Saliba, Walid; Zaina, Adnan","year":2024,"journal":"Diabetes, obesity & metabolism, 26(10), 4646-4652","doi":"10.1111/dom.15828","pmid":"39109455","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08526","title":"The Antiobesity Effect and Safety of GLP-1 Receptor Agonist in Overweight/Obese Adolescents Without Diabetes Mellitus: A Systematic Review and Meta-Analysis.","authors":"Katole, Nilesh T; Salankar, Harsh V; Khade, Ajay M; Kale, Jyoti S; Bankar, Nandkishor J; Gosavi, Punam; Dudhe, Bhushan; Mankar, Nishikant; Noman, Obaid","year":2024,"journal":"Cureus, 16(8), e66280","doi":"10.7759/cureus.66280","pmid":"39238716","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08527","title":"Weight Loss Therapies and Hypertension Benefits.","authors":"Katsi, Vasiliki; Manta, Eleni; Fragoulis, Christos; Tsioufis, Konstantinos","year":2024,"journal":"Biomedicines, 12(10)","doi":"10.3390/biomedicines12102293","pmid":"39457606","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review covers the blood pressure effects of all major approved obesity therapies. GLP-1 receptor agonists (liraglutide and semaglutide) and tirzepatide — peptide-based therapies — are among the treatments examined for their impact on hypertension. The shared pathophysiology linking obesity and hypertension includes overactivity of the renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system, insulin resistance, and disruption of the leptin pathway.\n\nThe review presents clinical evidence for how each therapy modifies blood pressure, positioning weight loss as a dual-benefit strategy for managing both obesity and hypertension simultaneously.","whyItMatters":"With obesity and hypertension both at epidemic levels globally, treatments that address both conditions simultaneously offer significant clinical value. GLP-1 receptor agonists and tirzepatide — all peptide-based drugs — have become blockbuster medications for weight loss. Understanding their blood pressure effects helps clinicians choose the most appropriate therapy for patients who have both conditions, potentially reducing the need for separate antihypertensive medications.","specificNumbers":"","methodology":"This is a narrative review article that compiles and synthesizes clinical trial data on the blood pressure effects of approved obesity therapies. It examines pharmacological treatments (phentermine/topiramate, orlistat, naltrexone/bupropion, liraglutide, semaglutide, tirzepatide) and bariatric surgery.","limitations":"As a narrative review, it may not capture all available literature systematically. The abstract does not report specific blood pressure reduction numbers for each therapy, making it difficult to compare magnitudes of effect. The review covers approved therapies as of 2024 and may not include emerging agents. Individual patient variability in blood pressure response to weight loss treatments is acknowledged but cannot be fully addressed in a review format."},{"rthcId":"RPEP-08528","title":"Prediction of peptide hormones using an ensemble of machine learning and similarity-based methods.","authors":"Kaur, Dashleen; Arora, Akanksha; Vigneshwar, Palani; Raghava, Gajendra P S","year":2024,"journal":"Proteomics, 24(20), e2400004","doi":"10.1002/pmic.202400004","pmid":"38803012","tags":[],"studyType":"computational","evidenceStrength":"moderate","keyFinding":"Researchers developed an ensemble computational method that can predict whether a peptide sequence functions as a hormone with 89.79% accuracy and an AUROC of 0.96. The approach combines similarity-based methods (BLAST, MERCI) with machine learning models (logistic regression achieving AUROC 0.93 alone). The ensemble method overcame limitations of similarity-based methods, which sometimes couldn't make predictions for novel sequences.\n\nThe team built a free web tool called HOPPred that can identify hormone-associated motifs within peptide sequences, making the prediction method accessible to researchers without computational expertise.","whyItMatters":"The human body uses hundreds of peptide hormones to regulate everything from metabolism to mood. Identifying which peptides act as hormones from sequence alone accelerates the discovery of new hormonal signaling molecules and helps researchers understand peptide function without expensive lab experiments. This tool could help identify previously unknown hormone peptides in genomic data.","specificNumbers":"1,174 hormonal + 1,174 non-hormonal peptides in dataset · AUROC 0.96 · Accuracy 89.79% · MCC 0.8 · Logistic regression alone: AUROC 0.93, 86% accuracy","methodology":"The researchers assembled a balanced dataset of 1,174 hormonal and 1,174 non-hormonal peptide sequences. They first developed similarity-based prediction methods using BLAST and MERCI software, then built machine learning models (including logistic regression and deep learning). Finally, they combined these into an ensemble method. Performance was evaluated on an independent validation dataset. The resulting tool was deployed as a web server (HOPPred).","limitations":"The model was trained on known peptide hormones, which represents a biased sample of well-studied organisms. Performance on completely novel peptide families or species with limited sequence data is unknown. The 89.79% accuracy means roughly 1 in 10 predictions may be wrong. The tool predicts hormonal function from sequence but cannot predict specific biological activity or receptor targets."},{"rthcId":"RPEP-08529","title":"A review of an investigational drug retatrutide, a novel triple agonist agent for the treatment of obesity.","authors":"Kaur, Manmeet; Misra, Saurav","year":2024,"journal":"European journal of clinical pharmacology, 80(5), 669-676","doi":"10.1007/s00228-024-03646-0","pmid":"38367045","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08530","title":"Use of glucagon-like-peptide 1 receptor agonist in the treatment of childhood obesity.","authors":"Kavarian, Patil N; Mosher, Tierra L; Abu El Haija, Marwa","year":2024,"journal":"Current opinion in pediatrics, 36(5), 542-546","doi":"10.1097/MOP.0000000000001379","pmid":"39254757","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08531","title":"An approach for the intracellular delivery of IgG via enzymatic ligation with a cell-permeable attenuated cationic amphiphilic lytic peptide.","authors":"Kawaguchi, Yoshimasa; Terada, Sakahiro; Futaki, Shiroh","year":2024,"journal":"Bioorganic & medicinal chemistry, 111, 117835","doi":"10.1016/j.bmc.2024.117835","pmid":"39053075","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08532","title":"Survodutide in MASH: bridging the gap between hepatic and systemic metabolic dysfunction.","authors":"Kaya, Eda; Yilmaz, Yusuf; Alkhouri, Naim","year":2024,"journal":"Expert opinion on investigational drugs, 33(12), 1167-1176","doi":"10.1080/13543784.2024.2441865","pmid":"39663847","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08533","title":"Glucagon-Like Peptide-1 Receptor Agonist Mediated Weight Loss and Diabetes Mellitus Benefits: A Narrative Review.","authors":"Kaye, Alan D; Lien, Nathan; Vuong, Christopher; Schmitt, Matthew H; Soorya, Yusra; Abubakar, Bushirat A; Muiznieks, Luke; Embry, Noah; Siddaiah, Harish; Kaye, Adam M; Shekoohi, Sahar; Varrassi, Giustino","year":2024,"journal":"Cureus, 16(12), e76101","doi":"10.7759/cureus.76101","pmid":"39840162","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08534","title":"The Role of Glucagon-Like Peptide-1 Agonists in the Treatment of Multiple Sclerosis: A Narrative Review.","authors":"Kaye, Alan D; Sala, Kelly R; Abbott, Brennan M; Dicke, Alexandra N; Johnson, Landyn D; Wilson, Parker A; Amarasinghe, Sam N; Singh, Naina; Ahmadzadeh, Shahab; Kaye, Adam M; Shekoohi, Sahar; Varrassi, Giustino","year":2024,"journal":"Cureus, 16(8), e67232","doi":"10.7759/cureus.67232","pmid":"39301360","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review synthesizes evidence showing multiple neuroprotective and anti-inflammatory effects of GLP-1 receptor agonists relevant to MS:\n\n- In animal models of experimental autoimmune encephalopathy (the standard MS model), GLP-1 agonists significantly delayed symptom onset and reduced disease severity\n- Treatment increased nerve myelination and brain weight in these models\n- In nerve crush injury models, GLP-1 agonists significantly increased the rate and density of nerve regeneration compared to controls\n- The mechanism likely involves GLP-1 receptors present on immune cells (macrophages, monocytes, lymphocytes), allowing the drugs to modulate inflammatory responses\n\nThe authors conclude that GLP-1 agonists show promise as both prophylactic and symptomatic treatments for MS.","whyItMatters":"Multiple sclerosis affects nearly 3 million people worldwide, and current treatments can have significant side effects. GLP-1 agonists are already FDA-approved, well-studied, and widely available — if their neuroprotective effects translate to humans, they could be rapidly repurposed for MS treatment with known safety profiles.","specificNumbers":"","methodology":"This is a narrative review synthesizing published preclinical studies on GLP-1 receptor agonists in animal models of multiple sclerosis (experimental autoimmune encephalopathy) and nerve injury. The authors surveyed evidence on anti-inflammatory mechanisms, neuroprotection, and nerve regeneration.","limitations":"All evidence reviewed comes from animal models, not human clinical trials. The exact mechanisms by which GLP-1 agonists affect MS remain unclear. Whether the drug concentrations that reach the brain in humans would be sufficient for neuroprotection is unknown. MS is a complex disease with multiple subtypes, and animal models may not capture all aspects of human disease."},{"rthcId":"RPEP-08535","title":"Peptide GLP-1 receptor agonists: From injection to oral delivery strategies.","authors":"Ke, Zhiqiang; Ma, Qianqian; Ye, Xiaonan; Wang, Yanlin; Jin, Yan; Zhao, Xinyuan; Su, Zhengding","year":2024,"journal":"Biochemical pharmacology, 229, 116471","doi":"10.1016/j.bcp.2024.116471","pmid":"39127152","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08536","title":"Glucagon-like peptide 1 agonists for type 2 diabetes, weight loss, or both?","authors":"Keedy, Chelsea A; Bland, Christopher M","year":2024,"journal":"JAAPA : official journal of the American Academy of Physician Assistants, 37(5), 12-14","doi":"10.1097/01.JAA.0000000000000017","pmid":"38662894","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08537","title":"Comparison of glucagon-like peptide-1 receptor agonists vs. placebo on any cardiovascular events in overweight or obese non-diabetic patients: a systematic review and meta-analysis.","authors":"Kelkar, Raveena; Barve, Nishad A; Kelkar, Rohan; Kharel, Sanjeev; Khanapurkar, Shalmi; Yadav, Rukesh","year":2024,"journal":"Frontiers in cardiovascular medicine, 11, 1453297","doi":"10.3389/fcvm.2024.1453297","pmid":"39323759","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08538","title":"Obesity in Adolescents: A Review.","authors":"Kelly, Aaron S; Armstrong, Sarah C; Michalsky, Marc P; Fox, Claudia K","year":2024,"journal":"JAMA, 332(9), 738-748","doi":"10.1001/jama.2024.11809","pmid":"39102244","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08539","title":"Real-world evaluation of the effects of tirzepatide in patients with type 2 diabetes mellitus.","authors":"Kelly, Michael S; Scopelliti, Emily M; Goodson, Kaylee E; Lo, Ching Mann Anne; Nguyen, Huelena X; Simon, Barbara","year":2024,"journal":"Diabetes, obesity & metabolism, 26(12), 5661-5668","doi":"10.1111/dom.15934","pmid":"39248221","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08540","title":"Semaglutide and blood pressure: an individual patient data meta-analysis.","authors":"Kennedy, Cormac; Hayes, Peter; Cicero, Arrigo F G; Dobner, Stephan; Le Roux, Carel W; McEvoy, John W; Zgaga, Lina; Hennessy, Martina","year":2024,"journal":"European heart journal, 45(38), 4124-4134","doi":"10.1093/eurheartj/ehae564","pmid":"39217502","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 3,136 participants from three randomized controlled trials, semaglutide 2.4 mg produced an overall systolic blood pressure reduction of -4.95 mmHg (95% CI -5.86 to -4.05) compared to placebo over 68 weeks.\n\nImportantly, the blood pressure reductions in people with hypertension (-4.78 mmHg) were similar to the overall population, rather than being larger as the researchers hypothesized. Those on semaglutide also reduced their anti-hypertensive medication intensity compared to placebo (score difference -0.51), suggesting that some of the blood pressure benefit may have been masked by concurrent medication reductions.","whyItMatters":"Semaglutide is already widely used for weight management and diabetes, so understanding its blood pressure effects has major implications. This analysis shows it offers meaningful blood pressure reduction as a bonus benefit, potentially allowing patients to simplify their medication regimens by reducing anti-hypertensive drugs.","specificNumbers":"","methodology":"The researchers conducted an individual patient data meta-analysis, pooling raw data from 3,136 participants across three large randomized controlled trials of semaglutide 2.4 mg vs. placebo over 68 weeks. Participants were grouped by hypertension status using several definitions, and blood pressure changes were compared using statistical models that adjusted for baseline differences.","limitations":"The blood pressure reductions in people with hypertension were not statistically significantly greater than in the overall population, partly because concurrent reductions in blood pressure medications may have blunted the observed effect. The study also only examined semaglutide 2.4 mg over 68 weeks, so effects at different doses or over longer periods remain unclear. Participants with resistant hypertension were a small subgroup, limiting conclusions for that population."},{"rthcId":"RPEP-08541","title":"Seasonal variation in expression patterns of anti-microbial peptides and activity of anti-oxidant defence enzymes in muga silkworm larvae, Antheraea assamensis Helfer.","authors":"Keot, Deepshikha; Dutta, Aashis; DAS, Manas","year":2024,"journal":"Journal of biosciences, 49","doi":null,"pmid":"39402959","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08542","title":"The role of pallidal substance P and neurokinin receptors in the consolidation of spatial memory of rats.","authors":"Kertes, Erika; Péczely, László; Ollmann, Tamás; László, Kristóf; Berta, Beáta; Kállai, Veronika; Zagorácz, Olga; Kovács, Anita; Szabó, Ádám; Karádi, Zoltán; Lénárd, László","year":2024,"journal":"The international journal of neuropsychopharmacology, 28(1)","doi":"10.1093/ijnp/pyaf002","pmid":"39775789","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08543","title":"Design and computational analysis of a novel Leptulipin-p28 fusion protein as a multitarget anticancer therapy in breast cancer.","authors":"Khalid, Sania; Rehman, Hafiz Muhammad; Al-Qassab, Yasamin; Ahmad, Irfan; Fatima, Tehreem; Mubasher, Mian Muhammad; Kalsoom, Maria; Nadeem, Tariq; Bashir, Hamid","year":2024,"journal":"Toxicology research, 13(5), tfae174","doi":"10.1093/toxres/tfae174","pmid":"39403123","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08544","title":"New horizon of the combined BCG vaccine with probiotic and liraglutide in augmenting beta cell survival via suppression of TXNIP/NLRP3 pyroptosis signaling in Streptozocin-Induced diabetes mellitestype-1 in rats.","authors":"Khalifa, Amira Karam; Abdelrahim, Dina Sayed; Mekawy, Dina Mohamed; Hamed, Reham Mohammad Raafat; Mohamed, Wafaa Rabee; Ramadan, Nagwa Mahmoud; Wael, Mostafa; Ellackany, Rawan; Albadawi, Emad Ali; Osman, Walla'a A","year":2024,"journal":"Heliyon, 10(20), e38932","doi":"10.1016/j.heliyon.2024.e38932","pmid":"39640632","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08545","title":"Development of in situ forming autologous fibrin scaffold incorporating synthetic teriparatide peptide for bone tissue engineering.","authors":"Khalili, Mohammad Reza; Molafilabi, Azam; Mousazadeh, Sepideh; Mehrabi, Arezou; Kiani, Jafar; Brouki Milan, Peiman; Ghasemi, Faezeh","year":2024,"journal":"The International journal of artificial organs, 47(9), 707-718","doi":"10.1177/03913988241262907","pmid":"39370606","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08546","title":"Intranasal delivery of glucagon-like peptide-1 to the brain for obesity treatment: opportunities and challenges.","authors":"Khan, Tanisha Tabassum Sayka; Sheikh, Zara; Maleknia, Simin; Oveissi, Farshad; Fathi, Ali; Abrams, Terence; Ong, Hui Xin; Traini, Daniela","year":2024,"journal":"Expert opinion on drug delivery, 21(7), 1081-1101","doi":"10.1080/17425247.2024.2387110","pmid":"39086086","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review establishes that nose-to-brain (N2B) delivery pathways — primarily along the olfactory and trigeminal nerves — can transport GLP-1 receptor agonists directly to brain regions involved in appetite regulation, circumventing the blood-brain barrier that limits subcutaneous delivery.\n\nKey challenges for nasal peptide delivery include nasal physiological barriers (mucociliary clearance, enzymatic degradation, limited epithelial permeability) and the peptide's physicochemical properties (size, charge, stability). Promising strategies to overcome these include cell permeation enhancers, mucoadhesive formulations that extend contact time with nasal epithelium, and nanocarrier systems. The review emphasizes that while preclinical results are encouraging, clinical effectiveness has not yet been demonstrated for this route of GLP-1 delivery.","whyItMatters":"Despite the transformative success of GLP-1 drugs, patient adherence is poor — up to 70% discontinue within the first year, largely due to GI side effects caused by high peripheral drug levels from subcutaneous injection. Intranasal nose-to-brain delivery could fundamentally change this: by targeting the brain directly, lower total drug doses could achieve the same appetite-suppressing effects while sparing the gut from the nausea-inducing exposure. This could also open new applications for GLP-1 drugs in cognitive disorders and addiction where brain targeting is essential.","specificNumbers":"","methodology":"This is a comprehensive narrative review published in Expert Opinion on Drug Delivery, synthesizing preclinical research on intranasal GLP-1 delivery, nasal anatomy and physiology, nose-to-brain transport mechanisms, and formulation strategies for nasal peptide delivery.","limitations":"The review is based primarily on preclinical data — no clinical trial has yet validated intranasal GLP-1 delivery for obesity treatment. The nose-to-brain pathway delivers very small quantities of drug, and it's unclear whether sufficient GLP-1 can reach appetite centers to produce clinically meaningful effects. Individual variation in nasal anatomy, mucus production, and nasal congestion could significantly affect delivery. The review acknowledges that successful preclinical data does not guarantee clinical effectiveness. Safety of chronic intranasal peptide administration (nasal irritation, olfactory effects) requires further study."},{"rthcId":"RPEP-08547","title":"Intra-arterial Peptide Receptor Radionuclide Therapy for the Treatment of Hepatic Neuroendocrine Tumor Metastases: Hope or Hype?","authors":"Khanjyan, Michael V; Fidelman, Nicholas","year":2024,"journal":"Seminars in interventional radiology, 41(1), 11-15","doi":"10.1055/s-0043-1778658","pmid":"38495261","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08548","title":"Liraglutide and resveratrol alleviated cyclosporin A induced nephrotoxicity in rats through improving antioxidant status, apoptosis and pro-inflammatory markers.","authors":"Kheira, Hend Samy; Elsayed, Gehad Ramadan; El-Adl, Mohamed","year":2024,"journal":"Biochemical and biophysical research communications, 730, 150337","doi":"10.1016/j.bbrc.2024.150337","pmid":"38986220","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Liraglutide (30 μg/kg/day) and/or resveratrol (20 mg/kg/day) given alongside cyclosporine A (25 mg/kg/day for 21 days) significantly improved kidney function tests and antioxidant activity in treated rats. Both treatments enhanced Bcl-2 levels (anti-apoptotic) while downregulating Bax (pro-apoptotic) in cyclosporine-treated kidneys. TNF-α immunostaining was negative to mildly positive in treated groups versus strongly positive in the cyclosporine-only group, confirming anti-inflammatory effects. Combination treatment (liraglutide + resveratrol) showed benefit across all measured markers.","whyItMatters":"Cyclosporine nephrotoxicity is a major clinical problem — virtually all transplant patients on cyclosporine develop some degree of kidney damage over time, and it's the leading cause of graft loss after organ transplantation. Finding a co-treatment that protects the kidneys without interfering with immunosuppression could significantly improve outcomes for millions of transplant recipients.","specificNumbers":"","methodology":"Rats were given cyclosporine A (25 mg/kg orally) for 21 days to induce kidney damage. Treatment groups received liraglutide (30 μg/kg subcutaneously daily), resveratrol (20 mg/kg orally), or both. At study end, serum and kidney tissue were analyzed for kidney function markers, antioxidant status (oxidative stress markers), apoptotic markers (Bcl-2, Bax), and pro-inflammatory markers (TNF-α immunohistochemistry).","limitations":"Rat model that may not fully replicate human cyclosporine nephrotoxicity. The 21-day treatment period is short compared to the years of cyclosporine use in transplant patients. The study did not assess whether liraglutide interferes with cyclosporine's immunosuppressive efficacy — a critical question for clinical translation. Specific quantitative data on kidney function improvement were not provided in the abstract. The liraglutide dose used in rats may not translate directly to human doses."},{"rthcId":"RPEP-08549","title":"Comparative Effectiveness of Second-Line Antihyperglycemic Agents for Cardiovascular Outcomes: A Multinational, Federated Analysis of LEGEND-T2DM.","authors":"Khera, Rohan; Aminorroaya, Arya; Dhingra, Lovedeep Singh; Thangaraj, Phyllis M; Pedroso Camargos, Aline; Bu, Fan; Ding, Xiyu; Nishimura, Akihiko; Anand, Tara V; Arshad, Faaizah; Blacketer, Clair; Chai, Yi; Chattopadhyay, Shounak; Cook, Michael; Dorr, David A; Duarte-Salles, Talita; DuVall, Scott L; Falconer, Thomas; French, Tina E; Hanchrow, Elizabeth E; Kaur, Guneet; Lau, Wallis C Y; Li, Jing; Li, Kelly; Liu, Yuntian; Lu, Yuan; Man, Kenneth K C; Matheny, Michael E; Mathioudakis, Nestoras; McLeggon, Jody-Ann; McLemore, Michael F; Minty, Evan; Morales, Daniel R; Nagy, Paul; Ostropolets, Anna; Pistillo, Andrea; Phan, Thanh-Phuc; Pratt, Nicole; Reyes, Carlen; Richter, Lauren; Ross, Joseph S; Ruan, Elise; Seager, Sarah L; Simon, Katherine R; Viernes, Benjamin; Yang, Jianxiao; Yin, Can; You, Seng Chan; Zhou, Jin J; Ryan, Patrick B; Schuemie, Martijn J; Krumholz, Harlan M; Hripcsak, George; Suchard, Marc A","year":2024,"journal":"Journal of the American College of Cardiology, 84(10), 904-917","doi":"10.1016/j.jacc.2024.05.069","pmid":"39197980","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Over 5.2 million patient-years of follow-up with 25,982 three-point MACE events: GLP-1RAs showed lower 3-point MACE risk than DPP4is (HR: 0.83, 95% CI: 0.70-0.98) and SUs (HR: 0.72, 95% CI: 0.58-0.88). SGLT2is showed similar patterns vs DPP4is (HR: 0.89, 95% CI: 0.79-1.00) and SUs (HR: 0.76, 95% CI: 0.65-0.89). No significant difference between SGLT2is and GLP-1RAs (HR: 1.06, 95% CI: 0.96-1.17). Same hierarchy for 4-point MACE (adding heart failure hospitalization). DPP4is outperformed SUs (HR: 0.87, 95% CI: 0.79-0.95).","whyItMatters":"No head-to-head randomized trials compare GLP-1RAs and SGLT2is for cardiovascular outcomes — and none are planned. This massive real-world analysis fills that evidence gap for the two most important modern diabetes drug classes. The finding that they're equally effective for cardiovascular protection is hugely practical: clinicians can choose between them based on other factors (kidney protection, weight loss, cost, patient preference) without sacrificing heart benefits.","specificNumbers":"","methodology":"Federated analysis across 10 international databases (LEGEND-T2DM network, 1992-2021). 1,492,855 patients with T2DM and CVD on metformin who initiated SGLT2is, GLP-1RAs, DPP4is, or sulfonylureas were identified. Large-scale propensity score models with active-comparator target trial emulation conducted pairwise comparisons. Cox proportional hazards models with random-effects meta-analysis combined site-specific estimates.","limitations":"Despite the massive sample size, this is observational data using electronic health records, which cannot fully replicate randomized trial conditions. Propensity score matching reduces but cannot eliminate confounding. The federated design means data quality varies across the 10 databases. Specific drugs within each class (e.g., semaglutide vs. liraglutide) were not compared. Follow-up duration and treatment adherence varied. The analysis covers data through 2021 and may not reflect newer agents or doses."},{"rthcId":"RPEP-08550","title":"Peptibodies: Bridging the gap between peptides and antibodies.","authors":"Khezri, Hamidhossein; Mostafavi, Mahdiyeh; Dabirmanesh, Bahareh; Khajeh, Khosro","year":2024,"journal":"International journal of biological macromolecules, 278(Pt 2), 134718","doi":"10.1016/j.ijbiomac.2024.134718","pmid":"39142490","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Peptibodies (peptide-Fc fusions) overcome key limitations of therapeutic peptides — including low stability, rapid clearance, and poor absorption — by fusing bioactive peptides to the Fc domain of immunoglobulin. This fusion enhances half-life, stability against proteolytic digestion, and overall efficacy while retaining the peptide's advantages of tissue penetration, cellular internalization, and low immunogenicity. Two peptibodies have achieved regulatory approval: romiplostim (EMA/FDA, for thrombocytopenia) and dulaglutide (FDA, a GLP-1 receptor agonist for type 2 diabetes).","whyItMatters":"Peptides represent an enormous therapeutic opportunity — they can target pathways that small molecules and antibodies cannot. But their short half-lives and instability have limited clinical success. Peptibodies solve this problem elegantly, and their success (particularly dulaglutide/Trulicity, one of the best-selling diabetes drugs) demonstrates the commercial and clinical viability of this approach. As more peptide targets are discovered, the peptibody platform could enable rapid translation to the clinic.","specificNumbers":"","methodology":"Narrative review covering the intrinsic properties of therapeutic peptides, the technology and production process for peptibodies, and their therapeutic applications across multiple disease areas.","limitations":"As a narrative review, this paper does not present original data. The review primarily focuses on approved peptibodies and those in development, but does not provide a systematic assessment of failure rates or challenges encountered in peptibody development. Manufacturing complexity and cost of Fc fusion proteins compared to simple peptides are acknowledged but not deeply explored."},{"rthcId":"RPEP-08551","title":"Treatment patterns of patients with migraine eligible for anti-CGRP pathway monoclonal antibodies.","authors":"Khodavirdi, Ani C; Multani, Jasjit K; Oh, Sam S; Vuvu, Fiston; Bensink, Mark E; Stockl, Karen M; Hawkins, Kevin; Chiang, Chia-Chun; Green, A Laine; Tepper, Stewart J","year":2024,"journal":"Frontiers in neurology, 15, 1433423","doi":"10.3389/fneur.2024.1433423","pmid":"39165264","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08552","title":"Current perspectives in obesity management: unraveling the impact of different therapy approach in real life obesity care.","authors":"Khorrami Chokami, Keyvan; Khorrami Chokami, Amir; Cammarata, Giuseppe; Piras, Grazia; Albertelli, Manuela; Gatto, Federico; Vera, Lara; Ferone, Diego; Boschetti, Mara","year":2024,"journal":"Journal of translational medicine, 22(1), 536","doi":"10.1186/s12967-024-05322-4","pmid":"38844956","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08553","title":"Enhanced Oral Efficacy of Semaglutide via an Ionic Nanocomplex with Organometallic Phyllosilicate in Type 2 Diabetic Rats.","authors":"Kim, Gyu Lin; Song, Jae Geun; Han, Hyo-Kyung","year":2024,"journal":"Pharmaceutics, 16(7)","doi":"10.3390/pharmaceutics16070886","pmid":"39065583","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08554","title":"Therapeutic Peptides, Proteins and their Nanostructures for Drug Delivery and Precision Medicine.","authors":"Kim, HaRam; Taslakjian, Boghos; Kim, Sarah; Tirrell, Matthew V; Guler, Mustafa O","year":2024,"journal":"Chembiochem : a European journal of chemical biology, 25(8), e202300831","doi":"10.1002/cbic.202300831","pmid":"38408302","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review covers several key aspects of peptide nanostructure-based drug delivery:\n\n- Synthesis and self-assembly techniques: peptides and proteins can form diverse nanostructures (nanotubes, fibers, micelles, vesicles) with tunable properties\n- Design strategies for enhanced stability, drug-loading capacity, and controlled release\n- Cell interaction mechanisms: receptor-mediated endocytosis and cell-penetrating capabilities enable targeted delivery\n- Biocompatibility and biomolecular recognition capacity make peptides ideal drug carriers\n- Applications in precision medicine: personalized therapies and disease-specific targeting for diagnostics and therapeutics\n- Cancer applications: tumor-specific targeting and delivery of therapeutic payloads","whyItMatters":"Current drug delivery systems often distribute drugs throughout the body, causing side effects. Peptide nanostructures can be programmed to deliver drugs specifically to diseased cells, improving effectiveness while reducing toxicity. Their biocompatibility (the body tolerates them well) and tunability make them ideal platforms for the growing field of precision medicine.","specificNumbers":"","methodology":"Comprehensive narrative review covering peptide and protein nanostructure design, synthesis, self-assembly, drug loading and release, cell interaction mechanisms, and applications in targeted drug delivery and precision medicine.","limitations":"As a review article, no original data is presented. Many of the discussed applications are still in preclinical stages. The translation from lab-scale peptide nanostructure fabrication to clinical manufacturing remains challenging. Issues like batch-to-batch reproducibility, in vivo stability, and regulatory pathways for peptide nanomedicines are not fully resolved."},{"rthcId":"RPEP-08555","title":"Dual Adjuvant-Loaded Peptide Antigen Self-Assembly Potentiates Dendritic Cell-Mediated Tumor Immunotherapy.","authors":"Kim, Jaehyun; Kang, Seyoung; Kim, Jisu; Yong, Seok-Beom; Lahiji, Shayan Fakhraei; Kim, Yong-Hee","year":2024,"journal":"Advanced science (Weinheim, Baden-Wurttemberg, Germany), 11(36), e2403663","doi":"10.1002/advs.202403663","pmid":"39073756","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08556","title":"GLP-1 increases preingestive satiation via hypothalamic circuits in mice and humans.","authors":"Kim, Kyu Sik; Park, Joon Seok; Hwang, Eunsang; Park, Min Jung; Shin, Hwa Yun; Lee, Young Hee; Kim, Kyung Min; Gautron, Laurent; Godschall, Elizabeth; Portillo, Bryan; Grose, Kyle; Jung, Sang-Ho; Baek, So Lin; Yun, Young Hyun; Lee, Doyeon; Kim, Eunseong; Ajwani, Jason; Yoo, Seong Ho; Güler, Ali D; Williams, Kevin W; Choi, Hyung Jin","year":2024,"journal":"Science (New York, N.Y.), 385(6707), 438-446","doi":"10.1126/science.adj2537","pmid":"38935778","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1RA administration to patients with obesity produced heightened preingestive satiation — feeling full before eating. Analysis of human and mouse brain tissue identified GLP-1 receptor neurons in the dorsomedial hypothalamus (DMH) as the key mediators.\n\nOptogenetic activation of DMH GLP-1R neurons directly caused satiation in mice. Calcium imaging showed these neurons actively encode preingestive satiation signals. GLP-1RA administration specifically increased DMH GLP-1R neuron activity during eating behavior. The mechanism involves interplay between DMH GLP-1R neurons and NPY/AgRP neurons in the arcuate nucleus — the brain's primary hunger-promoting neurons.","whyItMatters":"Despite GLP-1 drugs being prescribed to millions, no one fully understood which brain circuits they activate to reduce appetite. This Science paper identifies the specific neurons and circuit — DMH GLP-1R neurons interacting with arcuate NPY/AgRP neurons — providing the first complete picture. This knowledge could lead to even more targeted obesity treatments.","specificNumbers":"","methodology":"This translational study combined human clinical observations (GLP-1RA administration to patients with obesity), human and mouse brain tissue analysis, optogenetics (light-activated neuron control), and in vivo calcium imaging in mice to identify and characterize the brain circuits mediating GLP-1RA effects on satiation.","limitations":"The detailed circuit mapping was performed in mice, and while human brain samples and clinical observations were included, the full mechanistic validation in humans is still indirect. The study focused on preingestive satiation specifically; other mechanisms by which GLP-1RAs affect food intake (nausea, gastric emptying, reward pathways) were not the focus. Individual variation in DMH GLP-1R neuron responses was not extensively characterized."},{"rthcId":"RPEP-08557","title":"One-year Efficacy and Safety of Dulaglutide in Patients with Type 2 Diabetes and Chronic Kidney Disease: A Retrospective Study of Asian Patients.","authors":"Kim, Myung Jin; Kim, Hwi Seung; Cho, Yun Kyung; Jung, Chang Hee; Lee, Woo Je","year":2024,"journal":"Clinical therapeutics, 46(9), 683-688","doi":"10.1016/j.clinthera.2024.06.024","pmid":"39069432","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08558","title":"Low Molecular Weight Collagen Peptide (LMWCP) Promotes Hair Growth by Activating the Wnt/GSK-3β/β-Catenin Signaling Pathway.","authors":"Kim, Yujin; Lee, Jung Ok; Lee, Jung Min; Lee, Mun-Hoe; Kim, Hyeong-Min; Chung, Hee-Chul; Kim, Do-Un; Lee, Jin-Hee; Kim, Beom Joon","year":2024,"journal":"Journal of microbiology and biotechnology, 34(1), 17-28","doi":"10.4014/jmb.2308.08013","pmid":"37830229","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Low molecular weight collagen peptide (LMWCP) from fish promoted hair growth across multiple experimental models: it stimulated human dermal papilla cell proliferation and mitochondrial activity, increased secretion of growth factors (EGF, HB-EGF, FGF-4, FGF-6), boosted new hair follicle formation in a dose-dependent manner in patch assays, promoted human hair follicle growth ex vivo, and significantly stimulated hair growth when given orally to mice. The mechanism involved activation of the Wnt/GSK-3β/β-catenin signaling pathway, with upregulation of Wnt3a, β-catenin, VEGF, PCNA, Cyclin D1, and hair-specific keratins.","whyItMatters":"Hair loss affects hundreds of millions of people worldwide, yet treatment options are limited (mainly minoxidil and finasteride). Collagen peptides are widely available as supplements and generally well-tolerated. If these preclinical results translate to humans, oral collagen peptide supplements could provide a new, accessible approach to promoting hair growth through a well-characterized molecular pathway (Wnt/β-catenin) that is central to hair follicle biology.","specificNumbers":"Dose-dependent hair follicle neogeneration · Increased EGF, HB-EGF, FGF-4, FGF-6 · Upregulated Wnt3a, β-catenin, VEGF, PCNA, Cyclin D1 · Enhanced keratin Type I & II expression · Oral administration effective in mice","methodology":"Multi-model study: (1) In vitro testing on human dermal papilla cells (hDPCs) measuring proliferation, mitochondrial activity, and growth factor secretion; (2) Patch assay for hair follicle neogeneration; (3) Ex vivo human hair follicle growth assessment; (4) In vivo oral administration to telogenic C57BL/6 mice with histological and molecular analysis of back skin. Wnt/β-catenin pathway activation was confirmed through protein expression and nuclear translocation studies.","limitations":"While multiple models were used, the study is preclinical — no human clinical trial of oral LMWCP for hair growth was conducted. The mouse model (telogenic C57BL/6) tests hair cycle re-entry rather than reversal of actual hair loss conditions like androgenetic alopecia. The fish-derived collagen peptide composition may vary between sources and batches. Oral bioavailability of the specific active peptide fractions is not fully characterized."},{"rthcId":"RPEP-08559","title":"Usefulness of Once-Weekly GLP-1 Receptor Agonist Semaglutide on Glycemic Control in Subjects with Type 2 Diabetes Mellitus: Switching from the Same Class Dulaglutide in a Retrospective Observation Study.","authors":"Kimura, Tomohiko; Kubo, Masato; Takahashi, Kaio; Wamata, Ryo; Iwamoto, Yuichiro; Iwamoto, Hideyuki; Katakura, Yukino; Sanada, Junpei; Fushimi, Yoshiro; Shimoda, Masashi; Tatsumi, Fuminori; Nakanishi, Shuhei; Mune, Tomoatsu; Kaku, Kohei; Kaneto, Hideaki","year":2024,"journal":"Journal of diabetes research, 2024, 5880589","doi":"10.1155/2024/5880589","pmid":"38223524","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08560","title":"Patient-important outcomes in type 2 diabetes: The paradigm of the sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists.","authors":"Kintzoglanakis, Kyriakos; Diamantis, Christos; Mariolis, Anargiros; Paschou, Stavroula A","year":2024,"journal":"Diabetes & vascular disease research, 21(4), 14791641241269743","doi":"10.1177/14791641241269743","pmid":"39139128","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"SGLT-2 inhibitors and GLP-1 receptor agonists provide cardiovascular and renal protection beyond glucose lowering, reduce body weight and hypoglycemia risk, and improve diabetes-related distress, physical function, and health-related quality of life. Combined with basal insulin/GLP-1RA combinations, they enable treatment simplification from high-dose multi-injection insulin regimens. Additional benefits include reduced incidence of depression, cognitive decline, respiratory disease, gout, and arrhythmias — addressing the multimorbidity burden that complicates type 2 diabetes and degrades quality of life.","whyItMatters":"Diabetes management has historically focused on blood sugar numbers, but patients care more about how they feel, whether they'll have a heart attack, and how complicated their treatment is. This review makes the case for a paradigm shift — using GLP-1 drugs and SGLT-2 inhibitors earlier and more broadly because they improve the outcomes that actually matter to patients.","specificNumbers":"","methodology":"Narrative review synthesizing evidence from cardiovascular outcome trials, quality of life studies, and clinical research on the pleiotropic effects of SGLT-2 inhibitors and GLP-1 receptor agonists in type 2 diabetes.","limitations":"This is a narrative review without systematic methodology. The breadth of claimed benefits — from depression to gout to cognitive decline — draws from studies of varying quality and evidence strength. Some pleiotropic benefits are based on observational data and require confirmation in dedicated clinical trials. The review does not address cost barriers or access issues that limit real-world adoption."},{"rthcId":"RPEP-08561","title":"Collagen Peptide Supplementation during Training Does Not Further Increase Connective Tissue Protein Synthesis Rates.","authors":"Kirmse, Marius; Lottmann, Theo M; Volk, Nicola R; DE Marées, Markus; Holwerda, Andrew M; VAN Loon, Luc J C; Platen, Petra","year":2024,"journal":"Medicine and science in sports and exercise, 56(12), 2296-2304","doi":"10.1249/MSS.0000000000003519","pmid":"39086044","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08562","title":"Molecular and Cellular Neurobiology of Spreading Depolarization/Depression and Migraine: A Narrative Review.","authors":"Kitamura, Eiji; Imai, Noboru","year":2024,"journal":"International journal of molecular sciences, 25(20)","doi":"10.3390/ijms252011163","pmid":"39456943","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CSD triggers activation of the trigeminal nervous system and upregulates calcitonin gene-related peptide (CGRP) expression, establishing a direct mechanistic link between migraine aura and migraine pain. The review synthesizes evidence showing that CSD causes ionic changes and excitotoxicity in neurons and glia, which then propagate signals to the trigeminal system. Factors including genetics, obesity, and environmental conditions influence the threshold for CSD, representing potential therapeutic targets. Current CGRP-targeting drugs are evaluated for their expected ability to suppress CSD-related activity, and emerging therapies including intranasal insulin-like growth factor 1 and vagus nerve stimulation show promise in reducing CSD susceptibility.","whyItMatters":"Migraine affects over 1 billion people worldwide, yet its underlying mechanisms have long been debated. This review connects the dots between the visual aura that many migraine sufferers experience and the subsequent headache pain through the CGRP peptide pathway. This mechanistic understanding validates the growing class of CGRP-targeted drugs and helps identify who might benefit most from these therapies.","specificNumbers":"","methodology":"Narrative review synthesizing historical and contemporary studies on cortical spreading depolarization and its relationship to migraine, including imaging studies in humans, animal models, cellular and molecular mechanisms, and evaluation of current and emerging therapeutic approaches.","limitations":"As a narrative review, the paper selectively summarizes existing literature without systematic methodology. Much of the CSD-CGRP evidence comes from animal models, and direct confirmation of CSD in all migraine patients (especially those without aura) remains challenging. The review discusses emerging therapies whose clinical evidence is still limited."},{"rthcId":"RPEP-08563","title":"Treatment of Metabolic (Dysfunction)-Associated Fatty Liver Disease: Evidence from Randomized Controlled Trials-A Short Review.","authors":"Kitsios, Konstantinos; Trakatelli, Christina-Maria; Antza, Christina; Triantafyllou, Areti; Sarigianni, Maria; Kotsis, Vasilios","year":2024,"journal":"Metabolic syndrome and related disorders, 22(10), 703-708","doi":"10.1089/met.2024.0059","pmid":"39088384","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08564","title":"Characterization of genetic variants of GIPR reveals a contribution of β-arrestin to metabolic phenotypes.","authors":"Kizilkaya, Hüsün S; Sørensen, Kimmie V; Madsen, Jakob S; Lindquist, Peter; Douros, Jonathan D; Bork-Jensen, Jette; Berghella, Alessandro; Gerlach, Peter A; Gasbjerg, Lærke S; Mokrosiński, Jacek; Mowery, Stephanie A; Knerr, Patrick J; Finan, Brian; Campbell, Jonathan E; D'Alessio, David A; Perez-Tilve, Diego; Faas, Felix; Mathiasen, Signe; Rungby, Jørgen; Sørensen, Henrik T; Vaag, Allan; Nielsen, Jens S; Holm, Jens-Christian; Lauenborg, Jeannet; Damm, Peter; Pedersen, Oluf; Linneberg, Allan; Hartmann, Bolette; Holst, Jens J; Hansen, Torben; Wright, Shane C; Lauschke, Volker M; Grarup, Niels; Hauser, Alexander S; Rosenkilde, Mette M","year":2024,"journal":"Nature metabolism, 6(7), 1268-1281","doi":"10.1038/s42255-024-01061-4","pmid":"38871982","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08565","title":"Human sympathetic neuronal discharge and recruitment patterns regulate neuropeptide Y bioavailability.","authors":"Klassen, Stephen A; Limberg, Jacqueline K; Harvey, Ronée E; Wiggins, Chad C; Spafford, Julia E; Iannarelli, Nathaniel J; Senefeld, Jonathon W; Nicholson, Wayne T; Curry, Timothy B; Joyner, Michael J; Shoemaker, J Kevin; Baker, Sarah E","year":2024,"journal":"American journal of physiology. Heart and circulatory physiology, 327(6), H1599-H1605","doi":"10.1152/ajpheart.00639.2024","pmid":"39453430","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"NPY levels were positively associated with mean arterial pressure (β = 1.63, P = 0.002), total action potential clusters (β = 0.90, P = 0.005), and action potential frequency (β = 0.11, P = 0.003). This shows that both the rate of nerve firing and the pattern of nerve fiber recruitment regulate NPY release.\n\nNorepinephrine levels were also positively related to AP clusters (β = 19.50, P = 0.030) and AP frequency (β = 2.66, P = 0.014) but notably were not significantly related to mean arterial pressure (P = 0.133). This distinction suggests that NPY, rather than norepinephrine alone, may be the neurotransmitter more closely linked to blood pressure regulation through sympathetic nerve activity patterns.","whyItMatters":"Neuropeptide Y is one of the most abundant peptides in the nervous system and plays critical roles in blood pressure regulation, appetite, anxiety, and immune function. Understanding exactly how the nervous system controls NPY release has been a fundamental gap in neuroscience. This study provides the first human evidence that specific nerve firing strategies — not just overall nerve activity — determine NPY availability, opening new avenues for understanding cardiovascular regulation and potentially treating conditions like hypertension.","specificNumbers":"","methodology":"Six healthy individuals (5 females, mean age 27 years) underwent microneurography — a technique where a fine electrode is inserted into a peripheral nerve to record individual sympathetic nerve fiber activity. A continuous wavelet transform was used to detect individual sympathetic action potentials. Measurements were taken at baseline and during intravenous dexmedetomidine infusion (an α2-adrenergic agonist that modulates sympathetic activity). Arterial blood samples provided NPY and norepinephrine levels. Linear mixed-model regressions assessed relationships between nerve firing patterns and neurotransmitter levels.","limitations":"Very small sample size (n=6) limits statistical power and generalizability. The study was conducted in young, healthy individuals and may not reflect patterns in older adults or those with cardiovascular disease. Dexmedetomidine has multiple physiological effects beyond sympathetic modulation that could confound results. Microneurography measures a specific nerve bed and may not represent sympathetic activity to all vascular territories."},{"rthcId":"RPEP-08566","title":"Dramatic Changes in Thiopurine Metabolite Levels in a Patient With Inflammatory Bowel Disease Treated With Tirzepatide for Weight Loss.","authors":"Klein, Jeremy A; St-Pierre, Joëlle; Choi, David; Lopez, Jacqueline; Rubin, David T","year":2024,"journal":"ACG case reports journal, 11(11), e01544","doi":"10.14309/crj.0000000000001544","pmid":"39507506","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08567","title":"Perspectives in weight control in diabetes - Survodutide.","authors":"Klein, Thomas; Augustin, Robert; Hennige, Anita M","year":2024,"journal":"Diabetes research and clinical practice, 207, 110779","doi":"10.1016/j.diabres.2023.110779","pmid":"37330144","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08568","title":"Drug release profile of a novel exenatide long-term drug delivery system (OKV-119) administered to cats.","authors":"Klotsman, Michael; Anderson, Wayne H; Gilor, Chen","year":2024,"journal":"BMC veterinary research, 20(1), 211","doi":"10.1186/s12917-024-04051-6","pmid":"38762728","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08569","title":"GLP-1 receptor agonist exenatide uncouples food intake from hedonic and anticipatory regulation in non-human primates: insights from an operant meal schedule paradigm.","authors":"Knakker, Balázs; Inkeller, Judit; Kovács, Péter; Lendvai, Balázs; Hernádi, István","year":2024,"journal":"Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 50(2), 410-418","doi":"10.1038/s41386-024-01981-5","pmid":"39232188","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Acute exenatide (1 μg/kg subcutaneous) administered 1 hour before the first feeding session reduced food intake to uniformly very low levels across all meal schedule conditions, completely eliminating the anticipatory effect — where monkeys normally eat less in session 1 when expecting preferred food in session 2.\n\nExenatide induced hypoglycemia in a meal-schedule-dependent anticipatory pattern, suggesting metabolic anticipation was preserved even as eating behavior was suppressed. In the second feeding session, the positive contrast effect (preference for tastier food) was preserved but with a weaker residual effect specifically on consumption of the more palatable pellet. The authors conclude exenatide's effects evolve temporally from strong anorectic (appetite-suppressing) to weak anhedonic (pleasure-dampening) modulation.","whyItMatters":"One of the biggest concerns about GLP-1 weight loss drugs is whether they work by making food less pleasurable — which could contribute to depression or anhedonia in some patients. This study provides nuanced evidence that GLP-1 agonists primarily suppress the drive to eat while initially preserving hedonic experience, with pleasure-dampening effects appearing later and more weakly. Understanding this distinction is crucial for predicting psychological side effects.","specificNumbers":"","methodology":"Five adult male rhesus macaques were tested using a novel operant food intake paradigm with four meal schedule conditions. Two pellet types with different palatability values were offered in all combinations across two consecutive daily feeding sessions. Exenatide (1 μg/kg) was administered subcutaneously 1 hour before the first session. Food intake, pellet preferences, and blood glucose were measured across conditions.","limitations":"The study used only 5 male rhesus macaques, which is a very small sample size even for primate research. Only a single acute dose was tested — chronic dosing may produce different effects on hedonic regulation. The translation from macaque food preference behavior to human subjective experience of food pleasure is uncertain. Blood glucose changes (hypoglycemia) may have independently influenced feeding behavior."},{"rthcId":"RPEP-08570","title":"Lactic acid fermentation of kamaboko, a heated Alaska pollock surimi, enhances angiotensin I-converting enzyme inhibitory activity via fish protein hydrolysis.","authors":"Kobayashi, Kazuya; Takada, Natsuka; Matsubara, Yuki; Okuhara, Hiroaki; Oosaka, Masaki","year":2024,"journal":"The Journal of general and applied microbiology, 70(2)","doi":"10.2323/jgam.2024.01.003","pmid":"38281752","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08571","title":"Case report: Long-term efficacy and safety of semaglutide in the treatment of syndromic obesity in Prader Willi syndrome - case series and literature review.","authors":"Koceva, Andrijana; Mlekuš Kozamernik, Katarina; Janež, Andrej; Herman, Rok; Ferjan, Simona; Jensterle, Mojca","year":2024,"journal":"Frontiers in endocrinology, 15, 1528457","doi":"10.3389/fendo.2024.1528457","pmid":"39906041","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Three PWS patients without diabetes received semaglutide (0.5-2 mg weekly) with long-term follow-up. Patient 1: weight maintenance with prevention of further gain. Patient 2: 14.4% weight loss from baseline. Patient 3: 11% weight loss from baseline. One patient had previously undergone metabolic surgery.\n\nSemaglutide was well tolerated across all patients, including post-bariatric surgery. The variable response reflects the complex pathophysiology of PWS obesity, where dysfunction in satiety pathways, reward circuits, and hormonal regulation all contribute.","whyItMatters":"PWS affects about 1 in 15,000-25,000 births and is the most common genetic cause of severe obesity. Patients have insatiable hunger driven by brain dysfunction that makes conventional weight management nearly impossible. Finding that a GLP-1 drug can help — even in this extreme biological context — suggests semaglutide may work through mechanisms beyond simple appetite suppression.","specificNumbers":"","methodology":"Case series with long-term follow-up of three PWS patients treated with semaglutide at a single center. Treatment dosages ranged from 0.5 to 2 mg weekly. Clinical outcomes including weight change, tolerability, and safety were monitored. A literature review of GLP-1 RA use in PWS was also conducted.","limitations":"This is a case series of only three patients — the smallest possible clinical evidence. There was no control group, and individual responses varied significantly. The optimal dose and duration of semaglutide for PWS are unknown. Long-term effects on the distinctive metabolic and hormonal abnormalities of PWS were not comprehensively assessed. The results cannot be generalized to all PWS patients."},{"rthcId":"RPEP-08572","title":"A Risk-Difference Meta-Analysis for the Prophylactic Treatments of Chronic Migraine.","authors":"Kodounis, Michalis; Constantinidis, Theodoros S; Rizonaki, Konstantina; Drakou, Eleni; Zintzaras, Elias; Stefanidis, Ioannis; Mitsikostas, Dimos-Dimitrios; Dardiotis, Efthimios","year":2024,"journal":"Cureus, 16(6), e62458","doi":"10.7759/cureus.62458","pmid":"39022494","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"All four anti-CGRP monoclonal antibodies demonstrated invariably high and consistent efficacy, with NNTs (number needed to treat) ranging from 5 to 8 for achieving a 50% reduction in monthly migraine days. This means that for every 5-8 patients treated, one additional patient achieves meaningful improvement compared to placebo.\n\nIn contrast, onabotulinumtoxin A (Botox) showed a non-significant absolute risk difference with an NNT of 56 — meaning far more patients need treatment to achieve the same benefit. Topiramate results were contradictory between its two included studies (NNTs of 2 and 22). Safety profiles were similar across all treatments, with no significant differences in serious adverse events or study dropout rates among anti-CGRP mAbs.","whyItMatters":"Chronic migraine affects about 2% of the global population and is among the most disabling conditions worldwide. Until anti-CGRP antibodies arrived, treatment options were limited to repurposed drugs (topiramate, an epilepsy drug) and Botox injections. This analysis provides the first systematic indirect comparison showing that anti-CGRP antibodies are more consistently effective than these established treatments. The NNT metric is particularly useful for clinicians and patients making real-world treatment decisions.","specificNumbers":"","methodology":"Researchers searched MEDLINE and CENTRAL databases for phase 2b and phase 3 randomized controlled trials evaluating chronic migraine prophylaxis. Eight RCTs met inclusion criteria. Rather than pooling different drugs together, the authors used absolute risk difference (ARD) as the primary metric — a measure that directly translates into NNT and NNH (number needed to harm). This cross-trial indirect comparison approach was used because no head-to-head trials exist between anti-CGRP antibodies and standard treatments.","limitations":"This is an indirect comparison rather than a direct head-to-head trial, which introduces the possibility that differences between study populations, designs, and endpoints could confound the results. Only eight RCTs were included, and the small number of topiramate trials (2) produced contradictory results, limiting conclusions about that drug. The Botox studies used different trial designs than the CGRP antibody studies. The analysis does not account for long-term efficacy, cost-effectiveness, or patient preference factors."},{"rthcId":"RPEP-08573","title":"Chemical synthesis of grafted cyclotides using a \"plug and play\" approach.","authors":"Koehbach, Johannes; Muratspahić, Edin; Ahmed, Zakaria M; White, Andrew M; Tomašević, Nataša; Durek, Thomas; Clark, Richard J; Gruber, Christian W; Craik, David J","year":2024,"journal":"RSC chemical biology, 5(6), 567-571","doi":"10.1039/d4cb00008k","pmid":"38846076","tags":[],"studyType":"Laboratory/Methods Development","evidenceStrength":"Preliminary","keyFinding":"Researchers developed a modular \"plug and play\" method for synthesizing grafted cyclotides — plant-derived cyclic peptides used as scaffolds for drug design. The new approach bypasses the major bottleneck of oxidative folding by grafting bioactive sequences onto a pre-formed acyclic cyclotide-like scaffold.\n\nUsing this method, the team successfully produced cyclotide variants that target G protein-coupled receptors (GPCRs) with nanomolar affinities and potencies. The technique also enabled grafting of complex epitopes with additional disulfide bonds that were previously inaccessible through conventional chemical synthesis methods.","whyItMatters":"Cyclotides are extremely stable peptides that resist digestion and could potentially be taken orally — a holy grail for peptide drug design. But engineering them to carry therapeutic payloads has been limited by the difficulty of folding modified sequences. This new modular approach removes that barrier, potentially opening the door to a much wider range of cyclotide-based drugs targeting GPCRs, which are involved in nearly every major disease area.","specificNumbers":"Nanomolar affinity and potency at GPCRs · Modular grafting onto pre-formed scaffold · Accommodates epitopes with additional disulfide bonds","methodology":"The researchers developed a chemical synthesis strategy where bioactive peptide sequences are grafted onto a pre-formed acyclic cyclotide-like scaffold, rather than attempting to fold the entire modified cyclotide from scratch. They tested this approach with sequences known to be difficult to produce via conventional oxidative folding, including epitopes with extra disulfide bonds, and measured the resulting peptides' ability to bind and activate GPCRs.","limitations":"This is a proof-of-concept laboratory study focused on chemical synthesis methodology. No in vivo testing or pharmacokinetic data were reported. The approach was demonstrated with a limited number of target sequences, and broader applicability across diverse epitopes and GPCR targets remains to be established. Long-term stability and manufacturability at scale were not addressed."},{"rthcId":"RPEP-08574","title":"Interaction of serotonin/GLP-1 circuitry in a dual preclinical model for psychiatric disorders and metabolic dysfunction.","authors":"Kolling, Louis J; Khan, Kanza; Wang, Ruixiang; Pierson, Samantha R; Hartman, Benjamin D; Balasubramanian, Nagalakshmi; Guo, Deng-Fu; Rahmouni, Kamal; Marcinkiewcz, Catherine A","year":2024,"journal":"Psychiatry research, 337, 115951","doi":"10.1016/j.psychres.2024.115951","pmid":"38735240","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08575","title":"Acute Kidney and Liver Injury Associated With Low-Dose Liraglutide in an Obese Adolescent Patient.","authors":"Komargodski, Rinat; Wittenberg, Avigail; Bahat, Hilla; Rachmiel, Marianna","year":2024,"journal":"Pediatrics, 154(1)","doi":"10.1542/peds.2023-063719","pmid":"38864114","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08576","title":"Efficacy and safety of once-weekly subcutaneous semaglutide on weight loss in patients with overweight or obesity without diabetes mellitus-A systematic review and meta-analysis of randomized controlled trials.","authors":"Kommu, Sharath; Berg, Richard L","year":2024,"journal":"Obesity reviews : an official journal of the International Association for the Study of Obesity, 25(9), e13792","doi":"10.1111/obr.13792","pmid":"38923272","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08577","title":"Effects of dulaglutide and trelagliptin on beta-cell function in patients with type 2 diabetes: a randomized controlled study: DUET-beta study.","authors":"Kondo, Yoshinobu; Satoh, Shinobu; Terauchi, Yasuo","year":2024,"journal":"Diabetology international, 15(3), 474-482","doi":"10.1007/s13340-024-00717-6","pmid":"39101164","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08578","title":"Tirzepatide as an innovative treatment strategy in a pre-clinical model of obesity-driven endometrial cancer.","authors":"Kong, Weimin; Deng, Boer; Shen, Xiaochang; John, Catherine; Haag, Jennifer; Sinha, Nikita; Lee, Douglas; Sun, Wenchuan; Chen, Shuning; Zhang, Haomeng; Clontz, Angela; Hursting, Stephen D; Zhou, Chunxiao; Bae-Jump, Victoria","year":2024,"journal":"Gynecologic oncology, 191, 116-123","doi":"10.1016/j.ygyno.2024.10.004","pmid":"39388742","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08579","title":"Immunotherapy targeting tumor-associated antigen in a mouse model of head and neck cancer.","authors":"Kono, Michihisa; Wakisaka, Risa; Komatsuda, Hiroki; Hayashi, Ryusuke; Kumai, Takumi; Yamaki, Hidekiyo; Sato, Ryosuke; Nagato, Toshihiro; Ohkuri, Takayuki; Kosaka, Akemi; Ohara, Kenzo; Kishibe, Kan; Kobayashi, Hiroya; Hayashi, Tatsuya; Takahara, Miki","year":2024,"journal":"Head & neck, 46(8), 2056-2067","doi":"10.1002/hed.27703","pmid":"38390628","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08580","title":"Total and H-specific growth/differentiation factor 15 levels are unaffected by liraglutide or naltrexone/bupropion administration.","authors":"Konstantinidou, Sofia K; Argyrakopoulou, Georgia; Simati, Stamatia; Stefanakis, Konstantinos; Kokkinos, Alexander; Analitis, Antonis; Mantzoros, Christos S","year":2024,"journal":"Diabetes, obesity & metabolism, 26(8), 3147-3154","doi":"10.1111/dom.15642","pmid":"38757729","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08581","title":"Incretin-Based Multi-Agonist Peptides Are Neuroprotective and Anti-Inflammatory in Cellular Models of Neurodegeneration.","authors":"Kopp, Katherine O; Li, Yazhou; Glotfelty, Elliot J; Tweedie, David; Greig, Nigel H","year":2024,"journal":"Biomolecules, 14(7)","doi":"10.3390/biom14070872","pmid":"39062586","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08582","title":"Type 2 diabetes mellitus/obesity drugs: A neurodegenerative disorders savior or a bridge too far?","authors":"Kopp, Katherine O; Glotfelty, Elliot J; Li, Yazhou; Lahiri, Debomoy K; Greig, Nigel H","year":2024,"journal":"Ageing research reviews, 98, 102343","doi":"10.1016/j.arr.2024.102343","pmid":"38762101","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08583","title":"Dulaglutide and Dapagliflozin Combination Concurrently Improves the Endothelial Glycocalyx and Vascular and Myocardial Function in Patients with T2DM and Albuminuria vs. DPP-4i.","authors":"Korakas, Emmanouil; Thymis, John; Oikonomou, Evangelos; Mourouzis, Konstantinos; Kountouri, Aikaterini; Pliouta, Loukia; Pililis, Sotirios; Pavlidis, George; Lampsas, Stamatios; Katogiannis, Konstantinos; Palaiodimou, Lina; Tsivgoulis, Georgios; Siasos, Gerasimos; Ikonomidis, Ignatios; Raptis, Athanasios; Lambadiari, Vaia","year":2024,"journal":"Journal of clinical medicine, 13(24)","doi":"10.3390/jcm13247497","pmid":"39768420","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08584","title":"Semaglutide Concurrently Improves Vascular and Liver Indices in Patients With Type 2 Diabetes and Fatty Liver Disease.","authors":"Korakas, Emmanouil; Kountouri, Aikaterini; Pavlidis, George; Oikonomou, Evangelos; Vrentzos, Emmanouil; Michalopoulou, Eleni; Tsigkou, Vasiliki; Katogiannis, Konstantinos; Pliouta, Loukia; Balampanis, Konstantinos; Pililis, Sotirios; Malandris, Konstantinos; Tsapas, Apostolos; Siasos, Gerasimos; Ikonomidis, Ignatios; Lambadiari, Vaia","year":2024,"journal":"Journal of the Endocrine Society, 8(8), bvae122","doi":"10.1210/jendso/bvae122","pmid":"38979402","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08585","title":"PL3 CendR peptide shows specific uptake in cultured Y79 retinoblastoma cells with nucleolar accumulation.","authors":"Korhonen, Sonja; Bosch, Stef; Erkinheimo, Antero; Lajunen, Tatu; Rilla, Kirsi; Teesalu, Tambet; Subrizi, Astrid; Ruponen, Marika; Urtti, Arto; Reinisalo, Mika","year":2024,"journal":"European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 201, 106866","doi":"10.1016/j.ejps.2024.106866","pmid":"39067533","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08586","title":"The comparison of the antidiabetic effects of exenatide, empagliflozin, quercetin, and combination of the drugs in type 2 diabetic rats.","authors":"Korkmaz, Yasemin; Dik, Burak","year":2024,"journal":"Fundamental & clinical pharmacology, 38(3), 511-522","doi":"10.1111/fcp.12975","pmid":"38149676","tags":["glp-1-agonists","diabetes"],"studyType":"animal","evidenceStrength":"preliminary","keyFinding":"In type 2 diabetic rats, the GLP-1 agonist exenatide showed more pronounced antidiabetic effects than either empagliflozin (an SGLT2 inhibitor) or quercetin (a plant flavonoid) when used alone. However, the triple combination of all three drugs produced the best overall results.\n\nAll treatments lowered glucose, HbA1c, and triglyceride levels. Exenatide and the combination therapy were the only treatments to increase insulin levels. The combination was uniquely effective at decreasing leptin levels and HOMA-IR (insulin resistance). Exenatide improved HDL cholesterol and LDL levels, while the combination therapy showed the strongest combined antidiabetic and lipid-lowering effects.","whyItMatters":"Type 2 diabetes management often requires multiple drugs with complementary mechanisms. This study systematically compared a peptide drug (exenatide), a newer oral drug (empagliflozin), and a natural compound (quercetin) both alone and in combination. The finding that exenatide outperformed the others as monotherapy reinforces GLP-1 agonists' strong position in diabetes treatment. The superior results from triple combination therapy suggest that adding quercetin as a supplement alongside prescription medications could enhance metabolic outcomes.","specificNumbers":"n=67 rats · 7 groups · exenatide 10 μg/kg · empagliflozin 50 mg/kg · quercetin 50 mg/kg · 8-week treatment · all treatments ↓ glucose and HbA1c · combination uniquely ↓ HOMA-IR and leptin · exenatide ↑ HDL","methodology":"67 Wistar Albino male rats were divided into seven groups: healthy control, diabetes control, diabetes + sham, and four treatment groups (exenatide, empagliflozin, quercetin, and triple combination). Diabetes was induced and treatments were administered for 8 weeks. Outcomes measured included blood glucose, HbA1c, insulin, adiponectin, leptin, total antioxidant levels, LDL, HDL, triglycerides, HOMA-IR (insulin resistance), and HOMA-β (beta cell function).","limitations":"This is an animal study in rats with chemically induced diabetes, which may not fully replicate human type 2 diabetes. The drug doses were selected for rats and may not translate directly to human dosing. The 8-week treatment period is relatively short for assessing chronic diabetes management. The study does not report on potential drug interactions or adverse effects. Sample sizes per group (~9-10 rats) are small."},{"rthcId":"RPEP-08587","title":"The risk of depression, anxiety, and suicidal behavior in patients with obesity on glucagon like peptide-1 receptor agonist therapy.","authors":"Kornelius, Edy; Huang, Jing-Yang; Lo, Shih-Chang; Huang, Chien-Ning; Yang, Yi-Sun","year":2024,"journal":"Scientific reports, 14(1), 24433","doi":"10.1038/s41598-024-75965-2","pmid":"39424950","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08588","title":"Effects of Peptide Receptor Radiotherapy in Patients with Advanced Paraganglioma and Pheochromocytoma: A Nation-Wide Cohort Study.","authors":"Kornerup, Linda Skibsted; Andreassen, Mikkel; Knigge, Ulrich; Arveschoug, Anne Kirstine; Poulsen, Per Løgstup; Kjær, Andreas; Oturai, Peter Sandor; Grønbæk, Henning; Dam, Gitte","year":2024,"journal":"Cancers, 16(7)","doi":"10.3390/cancers16071349","pmid":"38611027","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08589","title":"Tirzepatide Prescribing Practices and Efficacy in Patients with Diabetes and Chronic Kidney Disease at a Large Tertiary Care Center in the United States.","authors":"Kosaraju, Sriya Amruta; Zhang, Rong M","year":2024,"journal":"Diabetes, metabolic syndrome and obesity : targets and therapy, 17, 3621-3628","doi":"10.2147/DMSO.S473319","pmid":"39376661","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08590","title":"Effects of Semaglutide on Symptoms, Function, and Quality of Life in Patients With Heart Failure With Preserved Ejection Fraction and Obesity: A Prespecified Analysis of the STEP-HFpEF Trial.","authors":"Kosiborod, Mikhail N; Verma, Subodh; Borlaug, Barry A; Butler, Javed; Davies, Melanie J; Jon Jensen, Thomas; Rasmussen, Søren; Erlang Marstrand, Peter; Petrie, Mark C; Shah, Sanjiv J; Ito, Hiroshi; Schou, Morten; Melenovský, Vojtěch; Abhayaratna, Walter; Kitzman, Dalane W","year":2024,"journal":"Circulation, 149(3), 204-216","doi":"10.1161/CIRCULATIONAHA.123.067505","pmid":"37952180","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08591","title":"Semaglutide in Patients with Obesity-Related Heart Failure and Type 2 Diabetes.","authors":"Kosiborod, Mikhail N; Petrie, Mark C; Borlaug, Barry A; Butler, Javed; Davies, Melanie J; Hovingh, G Kees; Kitzman, Dalane W; Møller, Daniél V; Treppendahl, Marianne B; Verma, Subodh; Jensen, Thomas J; Liisberg, Karoline; Lindegaard, Marie L; Abhayaratna, Walter; Ahmed, Fozia Z; Ben-Gal, Tuvia; Chopra, Vijay; Ezekowitz, Justin A; Fu, Michael; Ito, Hiroshi; Lelonek, Małgorzata; Melenovský, Vojtěch; Merkely, Bela; Núñez, Julio; Perna, Eduardo; Schou, Morten; Senni, Michele; Sharma, Kavita; van der Meer, Peter; Von Lewinski, Dirk; Wolf, Dennis; Shah, Sanjiv J","year":2024,"journal":"The New England journal of medicine, 390(15), 1394-1407","doi":"10.1056/NEJMoa2313917","pmid":"38587233","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 616 randomized patients with HFpEF, obesity (BMI ≥30), and type 2 diabetes over 52 weeks:\n\nPrimary endpoints:\n- KCCQ-CSS (symptoms/function): +13.7 vs +6.4 points; difference 7.3 points (95% CI: 4.1–10.4; P < 0.001)\n- Body weight: -9.8% vs -3.4%; difference -6.4 percentage points (95% CI: -7.6 to -5.2; P < 0.001)\n\nConfirmatory secondary endpoints:\n- 6-minute walk distance: +14.3 m difference (95% CI: 3.7–24.9; P = 0.008)\n- Hierarchical composite (death, HF events, KCCQ-CSS, walk distance): win ratio 1.58 (P < 0.001)\n- CRP level: treatment ratio 0.67 (P < 0.001) — 33% greater reduction in inflammation\n- Serious adverse events: 17.7% semaglutide vs 28.8% placebo — fewer with semaglutide","whyItMatters":"Heart failure with preserved ejection fraction (HFpEF) is the most common form of heart failure and has had very few effective treatments. This trial shows that semaglutide addresses a key driver — obesity — while simultaneously improving heart failure symptoms, exercise capacity, and inflammation. Published in the New England Journal of Medicine, it establishes a new treatment paradigm for this previously undertreated patient population.","specificNumbers":"","methodology":"Randomized, double-blind, placebo-controlled trial (STEP-HFpEF DM, NCT04916470) in patients with heart failure with preserved ejection fraction, BMI ≥30, and type 2 diabetes. Patients received once-weekly subcutaneous semaglutide 2.4 mg or placebo for 52 weeks. Co-primary endpoints were change in KCCQ-CSS (symptom score) and body weight. Confirmatory secondary endpoints included 6-minute walk distance, a hierarchical composite endpoint, and CRP levels.","limitations":"The trial duration was 52 weeks — longer-term outcomes including mortality benefits are unknown. Patients were specifically obese with type 2 diabetes and HFpEF, so results may not apply to all heart failure patients. The weight loss itself could account for some of the symptom improvement, making it difficult to isolate direct cardiac effects of semaglutide. The trial was funded by Novo Nordisk, the manufacturer of semaglutide."},{"rthcId":"RPEP-08592","title":"Semaglutide versus placebo in patients with heart failure and mildly reduced or preserved ejection fraction: a pooled analysis of the SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM randomised trials.","authors":"Kosiborod, Mikhail N; Deanfield, John; Pratley, Richard; Borlaug, Barry A; Butler, Javed; Davies, Melanie J; Emerson, Scott S; Kahn, Steven E; Kitzman, Dalane W; Lingvay, Ildiko; Mahaffey, Kenneth W; Petrie, Mark C; Plutzky, Jorge; Rasmussen, Søren; Rönnbäck, Cecilia; Shah, Sanjiv J; Verma, Subodh; Weeke, Peter E; Lincoff, A Michael","year":2024,"journal":"Lancet (London, England), 404(10456), 949-961","doi":"10.1016/S0140-6736(24)01643-X","pmid":"39222642","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 3,743 patients with HFpEF pooled from four randomized trials, semaglutide significantly reduced:\n\n- Cardiovascular death or worsening heart failure events: 5.4% vs 7.5% (HR 0.69, 95% CI 0.53-0.89, p=0.0045) — a 31% risk reduction\n- Worsening heart failure events alone: 2.8% vs 4.7% (HR 0.59, 95% CI 0.41-0.82, p=0.0019) — a 41% risk reduction\n\nCardiovascular death alone was not significantly reduced (3.1% vs 3.7%, HR 0.82, p=0.25). Serious adverse events were lower with semaglutide (29.9% vs 38.7%).","whyItMatters":"HFpEF affects millions of people and has been called the greatest unmet need in cardiovascular medicine because so few treatments work. This Lancet analysis provides the strongest evidence yet that semaglutide can prevent serious heart failure events — not just improve symptoms — in this population, potentially positioning it as one of the first effective therapies for HFpEF.","specificNumbers":"","methodology":"Post-hoc pooled, participant-level analysis of four randomized, double-blind, placebo-controlled trials: SELECT (atherosclerotic CVD with overweight/obesity), FLOW (type 2 diabetes with CKD), STEP-HFpEF, and STEP-HFpEF DM (obesity-related HFpEF). All participants with investigator-reported HFpEF were included (3,743 of 22,282 total participants). Semaglutide doses were 2.4 mg weekly in three trials and 1.0 mg weekly in FLOW. Analysis used intention-to-treat principles.","limitations":"This is a post-hoc pooled analysis, not a prospective trial specifically designed to test semaglutide for HFpEF event reduction. The four trials had different patient populations, entry criteria, and semaglutide doses. HFpEF was investigator-reported rather than adjudicated by a central committee. The effect on cardiovascular death alone was not significant, suggesting the benefit is primarily from reducing heart failure hospitalizations."},{"rthcId":"RPEP-08593","title":"SELECT: Glucagon-like peptide-1 receptor agonist in obese patients with cardiovascular disease in the absence of diabetes.","authors":"Kotit, Susy; Sous, Marina","year":2024,"journal":"Global cardiology science & practice, 2024(4), e202426","doi":"10.21542/gcsp.2024.26","pmid":"39351469","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08594","title":"Effectiveness of Anti-Calcitonin Gene-Related Peptide Medication in Vestibular Migraine: A Retrospective Cohort Study in an Asian Population.","authors":"Kouga, Teppei; Miwa, Toru; Sunami, Kishiko; Itoh, Yoshiaki","year":2024,"journal":"CNS drugs, 38(8), 637-648","doi":"10.1007/s40263-024-01094-z","pmid":"38809343","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08595","title":"Addition of Dulaglutide or Empagliflozin to Standard-of-Care Treatment: Effect on Liver Steatosis in Patients With Type 2 Diabetes Mellitus.","authors":"Koullias, Emmanouil; Papavdi, Maria; Athanasopoulos, Stavros; Mitrakou, Asimina; Deutsch, Melanie; Zoumpoulis, Pavlos; Manesis, Emmanuel; Thanopoulou, Anastasia; Koskinas, John","year":2024,"journal":"Cureus, 16(2), e53813","doi":"10.7759/cureus.53813","pmid":"38465109","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08596","title":"Anti-Diabetic Therapies and Cancer: From Bench to Bedside.","authors":"Kounatidis, Dimitris; Vallianou, Natalia G; Karampela, Irene; Rebelos, Eleni; Kouveletsou, Marina; Dalopoulos, Vasileios; Koufopoulos, Petros; Diakoumopoulou, Evanthia; Tentolouris, Nikolaos; Dalamaga, Maria","year":2024,"journal":"Biomolecules, 14(11)","doi":"10.3390/biom14111479","pmid":"39595655","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08597","title":"Inflammatory proteins associated with Alzheimer's disease reduced by a GLP1 receptor agonist: a post hoc analysis of the EXSCEL randomized placebo controlled trial.","authors":"Koychev, Ivan; Reid, Graham; Nguyen, Maggie; Mentz, Robert J; Joyce, Dan; Shah, Svati H; Holman, Rury R","year":2024,"journal":"Alzheimer's research & therapy, 16(1), 212","doi":"10.1186/s13195-024-01573-x","pmid":"39358806","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08598","title":"Endogenous Opioid Peptides After Floatation Therapy in Resistance-Trained Men.","authors":"Kraemer, William J; Caldwell, Lydia K; Post, Emily M; Volek, Jeff S; Hagen, Josh M; Newton, Robert U; Häkkinen, Keijo; Omonije, Oluseun; Maresh, Carl M","year":2024,"journal":"Journal of strength and conditioning research, 38(10), 1808-1812","doi":"10.1519/JSC.0000000000004931","pmid":"40168065","tags":["endorphins"],"studyType":"crossover-trial","evidenceStrength":"preliminary","keyFinding":"Floatation therapy (Float-REST) did not significantly change endogenous opioid peptide levels compared to a passive control recovery after heavy resistance exercise. Beta-endorphin (β-End) rose significantly after the intense squat workout in both conditions — as expected — but floatation therapy didn't produce any additional increase or differential pattern.\n\nProenkephalin (ProEnk), a precursor to the enkephalin family of opioid peptides, showed no significant changes in response to either the exercise or the floatation recovery. Its plasma levels remained detectable and stable throughout, suggesting it may function through local (paracrine) rather than systemic signaling.\n\nThe practical takeaway: the deep relaxation people commonly report from float tanks after exercise is probably not driven by changes in circulating opioid peptides. Beta-endorphin stayed consistently elevated from the workout itself regardless of recovery method.","whyItMatters":"Float tanks have become popular in athletic recovery, with many users reporting profound relaxation and reduced soreness. This study tested whether that relaxation is mediated by opioid peptides — the body's natural painkillers. The finding that it isn't means the subjective benefits of floatation likely come from other mechanisms (sensory deprivation, muscle relaxation, reduced cortisol) rather than an extra endorphin boost. This helps separate the science from the marketing around float therapy.","specificNumbers":"n=11 · Trained men (squat 1RM: 153.1±20.1 kg) · 6×10 back squats at 80% 1RM · 1-hour float session · 5 blood draws over 48 hours · β-End significantly increased post-exercise (p≤0.05) · No differential effect of floatation · ProEnk stable throughout","methodology":"Within-subject crossover controlled design. 11 resistance-trained men completed two exercise blocks separated by a 2-week washout. Each block involved the same high-intensity protocol (6 sets of 10 back squats at 80% of their one-rep max with 2-minute rest). After one session, they did a 1-hour float (Float-REST); after the other, a passive sensory-stimulating control. Blood was drawn at 5 timepoints: before exercise, immediately after, after recovery, 24 hours later, and 48 hours later. Beta-endorphin and proenkephalin were measured using ELISA immunoassays. Differences were assessed using repeated-measures ANOVA.","limitations":"Very small sample (n=11) of young, trained men limits generalizability. Only two opioid peptides were measured — other endogenous opioids (dynorphins, endomorphins) weren't assessed. The 1-hour float session is a specific protocol and different durations may have different effects. Subjective relaxation data wasn't correlated with peptide levels, so we can't directly test whether relaxation and peptide changes are dissociated. The study can't rule out localized opioid peptide changes in the brain that wouldn't appear in blood samples."},{"rthcId":"RPEP-08599","title":"The Therapeutic Potential of GLP-1 Receptor Agonists in the Management of Hidradenitis Suppurativa: A Systematic Review of Anti-Inflammatory and Metabolic Effects.","authors":"Krajewski, Piotr K; Złotowska, Aleksandra; Szepietowski, Jacek C","year":2024,"journal":"Journal of clinical medicine, 13(21)","doi":"10.3390/jcm13216292","pmid":"39518431","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08600","title":"Plasma calcitonin gene-related peptide levels in idiopathic intracranial hypertension: an exploratory study.","authors":"Krajnc, Nik; Frank, Florian; Macher, Stefan; Michl, Martin; Müller, Nina; Maier, Sarah; Zaic, Sina; Wöber, Christian; Pemp, Berthold; Broessner, Gregor; Bsteh, Gabriel","year":2024,"journal":"The journal of headache and pain, 25(1), 92","doi":"10.1186/s10194-024-01799-y","pmid":"38834953","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08601","title":"Oral GLP-1 Receptor Agonists for Weight Loss.","authors":"Krinsky, Dana; Marcucci, Avraham; Mullally, Jamie A; Frishman, William H","year":2024,"journal":"Cardiology in review","doi":"10.1097/CRD.0000000000000833","pmid":"39688941","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08602","title":"Safety and Efficacy of GLP-1 Receptor Agonists in Type 2 Diabetes Mellitus with Advanced and End-Stage Kidney Disease: A Systematic Review and Meta-Analysis.","authors":"Krisanapan, Pajaree; Sanpawithayakul, Kanokporn; Pattharanitima, Pattharawin; Thongprayoon, Charat; Miao, Jing; Mao, Michael A; Suppadungsuk, Supawadee; Tangpanithandee, Supawit; Craici, Iasmina M; Cheungpasitporn, Wisit","year":2024,"journal":"Diseases (Basel, Switzerland), 12(1)","doi":"10.3390/diseases12010014","pmid":"38248365","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 8 studies (27,639 patients), GLP-1 RAs in advanced CKD/ESKD patients showed:\n- Significant reduction in cardiothoracic ratio (SMD -1.2%, 95% CI -2.0 to -0.4)\n- Significant reduction in pro-BNP (SMD -335.9 pmol/L, 95% CI -438.9 to -232.8)\n- Significant decrease in mean blood glucose (SMD -1.1 mg/dL, 95% CI -1.8 to -0.3)\n- Significant weight loss (SMD -2.2 kg, 95% CI -2.9 to -1.5)\n- No significant change in systolic blood pressure or one-year mortality\n\nSafety: GLP-1 RAs were associated with 3.8x higher risk of nausea and 35.7x higher risk of vomiting, but no significant increase in hypoglycemia risk.","whyItMatters":"Advanced kidney disease patients have historically been excluded from major GLP-1 drug trials, leaving clinicians with little evidence to guide treatment decisions for this high-risk population. This meta-analysis fills a critical evidence gap, showing that GLP-1 drugs can be used safely and effectively even in patients with severely compromised kidney function — potentially expanding treatment access to millions of patients worldwide.","specificNumbers":"","methodology":"Systematic review and meta-analysis searching MEDLINE, EMBASE, and Cochrane databases through October 2023. Eight studies were included (5 trials, 3 cohort studies) involving 27,639 patients with T2DM and advanced CKD or ESKD. Risk of bias was assessed using ROBINS-I for non-randomized studies and Cochrane RoB 2 for RCTs. Protocol registered in PROSPERO (CRD 42023398452).","limitations":"The limited number of studies (8 total) and heterogeneity between trials and cohort studies constrain the strength of conclusions. The 35.7-fold increase in vomiting risk is clinically significant, especially for dialysis patients who may already struggle with nausea. One-year mortality showed no difference, but follow-up may be too short to detect long-term survival benefits. The analysis could not determine optimal dosing for patients with varying degrees of kidney impairment."},{"rthcId":"RPEP-08603","title":"Cellular metabolism of substance P produces neurokinin-1 receptor peptide agonists with diminished cyclic AMP signaling.","authors":"Kriska, Tamas; Natarajan, Jayashree; Herrnreiter, Anja; Park, Sang-Kyu; Pfister, Sandra L; Thomas, Michael J; Widiapradja, Alexander; Levick, Scott P; Campbell, William B","year":2024,"journal":"American journal of physiology. Cell physiology, 327(1), C151-C167","doi":"10.1152/ajpcell.00103.2024","pmid":"38798270","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08604","title":"Tirzepatide and blood pressure reduction: stratified analyses of the SURMOUNT-1 randomised controlled trial.","authors":"Krumholz, Harlan M; de Lemos, James A; Sattar, Naveed; Linetzky, Bruno; Sharma, Palash; Mast, Casey J; Ahmad, Nadia N; Bunck, Mathijs C; Stefanski, Adam","year":2024,"journal":"Heart (British Cardiac Society), 110(19), 1165-1171","doi":"10.1136/heartjnl-2024-324170","pmid":"39084707","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08605","title":"One-Year and Five-Year Outcomes in Medication Overuse Headache: A Real-World Study.","authors":"Krymchantowski, Abouch; Jevoux, Carla; Krymchantowski, Ana Gabriela; Dominguez-Moreno, Rogelio; Pereira Silva-Néto, Raimundo","year":2024,"journal":"Cureus, 16(10), e72347","doi":"10.7759/cureus.72347","pmid":"39463910","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 142 patients with chronic migraine and medication overuse headache (MOH), treatment with abrupt medication withdrawal, conventional preventive therapy, and optional anti-CGRP monoclonal antibodies produced significant long-term improvements. Patients started with an average of 25.2 headache days per month.\n\nAt one-year follow-up, 51.4% of patients achieved a ≥75% reduction in headache days per month (HDM). By the five-year follow-up, this improved to 70.4% achieving ≥75% reduction in HDM, demonstrating that outcomes continued to improve over time with sustained treatment.","whyItMatters":"Medication overuse headache affects millions worldwide and creates a vicious cycle where the very medications used to treat headaches end up making them worse. This study provides rare long-term real-world data showing that a structured approach — stopping overused medications and adding modern preventive treatments like anti-CGRP antibodies — can produce sustained improvements over five years, with outcomes actually improving over time rather than plateauing.","specificNumbers":"","methodology":"This was a single-center, prospective, descriptive study at a tertiary headache center in Brazil. Researchers enrolled 142 consecutive patients diagnosed with chronic migraine and medication overuse headache through convenience sampling. All patients underwent abrupt withdrawal of overused medications, received transition therapy, and were started on preventive treatments with optional anti-CGRP monoclonal antibodies. Clinical data including headache days per month were collected at baseline, one year, and five years.","limitations":"This was a single-center study in Brazil using convenience sampling, limiting generalizability. There was no control group or randomization, so improvements cannot be attributed specifically to anti-CGRP antibodies versus other components of the treatment protocol. The study did not report what proportion of patients received anti-CGRP antibodies versus conventional preventives only. Dropout rates over five years were not detailed in the abstract."},{"rthcId":"RPEP-08606","title":"Racial and Ethnic Disparities in Prescribing of GLP-1 Receptor Agonists in the United States: A Retrospective Cohort Analysis.","authors":"Kukhareva, Polina V; Facelli, Julio C; O'Brien, Matthew J; Gouripeddi, Ram; Kawamoto, Kensaku; Zhang, Yue; Reddy, Deepika; Malone, Daniel C","year":2024,"journal":"medRxiv : the preprint server for health sciences","doi":"10.1101/2024.10.28.24316312","pmid":"39574878","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08607","title":"Assessing the therapeutic and toxicological profile of novel GLP-1 receptor agonists for type 2 diabetes.","authors":"Kukova, Lidiya; Munir, Kashif M; Sayeed, Ahmed; Davis, Stephen N","year":2024,"journal":"Expert opinion on drug metabolism & toxicology, 20(10), 939-952","doi":"10.1080/17425255.2024.2401589","pmid":"39268978","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08608","title":"Amphiphilic shuttle peptide delivers base editor ribonucleoprotein to correct the CFTR R553X mutation in well-differentiated airway epithelial cells.","authors":"Kulhankova, Katarina; Cheng, Anna X; Traore, Soumba; Auger, Maud; Pelletier, Mia; Hervault, Maxime; Wells, Kevin D; Green, Jonathan A; Byrne, Addison; Nelson, Benjamin; Sponchiado, Mariana; Boosani, Chandra; Heffner, Caleb S; Snow, Kathy J; Murray, Stephen A; Villacreses, Raul A; Rector, Michael V; Gansemer, Nicholas D; Stoltz, David A; Allamargot, Chantal; Couture, Frédéric; Hemez, Colin; Hallée, Stéphanie; Barbeau, Xavier; Harvey, Mario; Lauvaux, Coraline; Gaillet, Bruno; Newby, Gregory A; Liu, David R; McCray, Paul B; Guay, David","year":2024,"journal":"Nucleic acids research, 52(19), 11911-11925","doi":"10.1093/nar/gkae819","pmid":"39315713","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08609","title":"Cell-Penetrating Chaperone Nuc1 for Small- and Large-Molecule Delivery Into Retinal Cells and Tissues.","authors":"Kumar, Binit; Mishra, Manish; Talreja, Deepa; Cashman, Siobhan; Kumar-Singh, Rajendra","year":2024,"journal":"Investigative ophthalmology & visual science, 65(8), 31","doi":"10.1167/iovs.65.8.31","pmid":"39028980","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08610","title":"Enhanced Antibacterial, Anti-Inflammatory, and Antibiofilm Activities of Tryptophan-Substituted Peptides Derived from Cecropin A-Melittin Hybrid Peptide BP100.","authors":"Kumar, Sukumar Dinesh; Kim, Eun Young; Radhakrishnan, Naveen Kumar; Bang, Jeong Kyu; Yang, Sungtae; Shin, Song Yub","year":2024,"journal":"Molecules (Basel, Switzerland), 29(22)","doi":"10.3390/molecules29225231","pmid":"39598621","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08611","title":"Understanding the Dynamics of Human Defensin Antimicrobial Peptides: Pathogen Resistance and Commensal Induction.","authors":"Kumaresan, Veenayohini; Kamaraj, Yoganathan; Subramaniyan, Satheeshkumar; Punamalai, Ganesh","year":2024,"journal":"Applied biochemistry and biotechnology, 196(10), 6993-7024","doi":"10.1007/s12010-024-04893-8","pmid":"38478321","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08612","title":"GLP-1 Receptor Agonists: A Promising Therapy for Modern Lifestyle Diseases with Unforeseen Challenges.","authors":"Kupnicka, Patrycja; Król, Małgorzata; Żychowska, Justyna; Łagowski, Ryszard; Prajwos, Eryk; Surówka, Anna; Chlubek, Dariusz","year":2024,"journal":"Pharmaceuticals (Basel, Switzerland), 17(11)","doi":"10.3390/ph17111470","pmid":"39598383","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08613","title":"Effects of long-term desmopressin treatment for nocturia in older people.","authors":"Kurose, Hirofumi; Ueda, Kosuke; Chikui, Katsuaki; Uemura, Keiichiro; Nishihara, Kiyoaki; Nakiri, Makoto; Suekane, Shigetaka; Igawa, Tsukasa","year":2024,"journal":"International journal of urology : official journal of the Japanese Urological Association, 31(10), 1114-1120","doi":"10.1111/iju.15530","pmid":"39007527","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 133 men (mean age 77.7 years) with nocturnal polyuria treated with desmopressin 50 μg:\n\n- 87.6% showed improved symptoms at 52 weeks (score ≤ 3)\n- Improvements sustained across all efficacy endpoints: nocturnal urinary frequency, nocturnal urinary volume, hours of undisturbed sleep, nocturnal polyuria index, initial nocturnal urinary volume, and daily urinary frequency\n- Improvements were measured at 1, 4, 12, 24, and 52 weeks\n- BNP (brain natriuretic peptide) level rose over the year, but cardiothoracic ratio on chest X-ray was unchanged\n- Body composition was not significantly affected\n- Long-term administration deemed effective and safe in older men","whyItMatters":"Nocturia is one of the most common and bothersome urinary symptoms in older adults, severely affecting sleep quality and increasing fall risk. While desmopressin is effective, concerns about water retention and cardiac effects in elderly patients have limited long-term use. This study provides reassuring real-world evidence that the peptide drug can be used safely for at least one year in older men.","specificNumbers":"","methodology":"Retrospective study at Chikugo City Hospital (August 2020 – December 2022) involving 133 men with nocturnal polyuria. Patients received an initial dose of desmopressin 50 μg. Efficacy was assessed using 3-day frequency-volume charts at baseline and 1, 4, 12, 24, and 52 weeks. Safety was monitored through BNP levels and chest X-ray (cardiothoracic ratio) at baseline and 52 weeks.","limitations":"This was a retrospective, single-center study without a control group or blinding. The BNP increase, while not accompanied by cardiac structural changes, warrants monitoring. Only men were included, so results may not apply to women. The study did not track sodium levels, which can drop dangerously with desmopressin use (hyponatremia). Some patients may have dropped out due to side effects, potentially biasing the 87.6% improvement rate."},{"rthcId":"RPEP-08614","title":"Semaglutide in Heart Failure With Preserved Ejection Fraction: Exploring Recent Evidence in Therapeutic Potential for the Obese Population.","authors":"Kusayev, Josef; Levy, Yisrael; Weininger, David; Frishman, William H; Aronow, Wilbert S","year":2024,"journal":"Cardiology in review","doi":"10.1097/CRD.0000000000000726","pmid":"38757954","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08615","title":"Functional changes in the heart after sacubitril/valsartan use in 5 hemodialysis patients with hypertension. Case report.","authors":"Kuwae, Noriko","year":2024,"journal":"CEN case reports, 13(4), 233-239","doi":"10.1007/s13730-023-00833-3","pmid":"37995053","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08616","title":"Coordinated ASBT and EGFR Mechanisms for Optimized Liraglutide Nanoformulation Absorption in the GI Tract.","authors":"Kweon, Seho; Park, Seong Jin; Lee, Ha Kyeong; Kang, Seo Hee; Chang, Kwan-Young; Choi, Jeong Uk; Park, Jooho; Shim, Jung-Hyun; Park, Jin Woo; Byun, Youngro","year":2024,"journal":"International journal of nanomedicine, 19, 2973-2992","doi":"10.2147/IJN.S442617","pmid":"38544951","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08617","title":"Real-World Use of Semaglutide for Weight Management: Patient Characteristics and Dose Titration-A Danish Cohort Study.","authors":"Ladebo, Louise; Ernst, Martin T; Mailhac, Aurélie; Dirksen, Carsten; Bojsen-Møller, Kirstine N; Pottegård, Anton","year":2024,"journal":"Diabetes care, 47(10), 1834-1837","doi":"10.2337/dc24-1082","pmid":"39106205","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08618","title":"Does glucose-dependent insulinotropic polypeptide receptor blockade as well as agonism have a role to play in management of obesity and diabetes?","authors":"Lafferty, Ryan A; Flatt, Peter R; Gault, Victor A; Irwin, Nigel","year":2024,"journal":"The Journal of endocrinology, 262(2)","doi":"10.1530/JOE-23-0339","pmid":"38861364","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08619","title":"NPYR modulation: Potential for the next major advance in obesity and type 2 diabetes management?","authors":"Lafferty, Ryan A; Flatt, Peter R; Irwin, Nigel","year":2024,"journal":"Peptides, 179, 171256","doi":"10.1016/j.peptides.2024.171256","pmid":"38825012","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08620","title":"Annulus Fibrosus Injury Induces Acute Neuroinflammation and Chronic Glial Response in Dorsal Root Ganglion and Spinal Cord-An In Vivo Rat Discogenic Pain Model.","authors":"Lai, Alon; Iliff, Denise; Zaheer, Kashaf; Gansau, Jennifer; Laudier, Damien M; Zachariou, Venetia; Iatridis, James C","year":2024,"journal":"International journal of molecular sciences, 25(3)","doi":"10.3390/ijms25031762","pmid":"38339040","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08621","title":"Design of Proteolytic-Resistant Antifungal Peptides by Utilizing Minimum d-Amino Acid Ratios.","authors":"Lai, Zhenheng; Yuan, Xiaojie; Chen, Wenwen; Chen, Hongyu; Li, Bowen; Bi, Zhongpeng; Lyu, Yinfeng; Shan, Anshan","year":2024,"journal":"Journal of medicinal chemistry, 67(13), 10891-10905","doi":"10.1021/acs.jmedchem.4c00394","pmid":"38934239","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08622","title":"Can Unmet Needs Be Addressed by Adjunctive Therapies? Findings from a Patient Perspectives Survey in Adults with Type 1 Diabetes.","authors":"Lamaro, Bella D; Greenfield, Jerry R; Snaith, Jennifer R","year":2024,"journal":"Journal of patient experience, 11, 23743735241257811","doi":"10.1177/23743735241257811","pmid":"38799027","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In a survey of 133 adults with type 1 diabetes, 28% reported unmet treatment needs, primarily in glycemic control, management-related fatigue, and weight management. An overwhelming 94% indicated willingness to use adjunctive therapies alongside insulin. When presented with masked drug profiles, 94% preferred liraglutide's risk-benefit profile (1.8 mg, then 0.6 mg) over placebo. Preferred administration routes were daily tablets (66%) and weekly injections (32%). Semi-structured interviews with 20 participants confirmed and extended these findings.","whyItMatters":"GLP-1 receptor agonists are not currently approved for type 1 diabetes, yet this survey shows that T1D patients have significant unmet needs that align closely with GLP-1RA benefits — particularly weight management, reduced glycemic variability, and potentially reduced insulin doses. Understanding patient willingness and preferences is essential for designing clinical trials and guiding regulatory decisions about expanding GLP-1RA indications to T1D.","specificNumbers":"n=133 surveyed · 28% unmet needs · 94% willing to use adjunctive therapy · 94% preferred liraglutide profile · 66% preferred daily tablets · 32% preferred weekly injections · n=20 interviewed","methodology":"Mixed-methods study: (1) Quantitative online survey of 133 adults with T1D assessing demographics, management data, priorities, satisfaction, and willingness to use adjunctive therapies; (2) Risk-benefit analysis using three masked drug profiles (liraglutide 1.8 mg, 0.6 mg, and placebo); (3) Semi-structured qualitative interviews with 20 respondents for deeper insights.","limitations":"Self-reported data may be subject to selection bias — individuals motivated to seek new treatments may be overrepresented. The sample size of 133 is modest. The masked drug profiles assessed willingness based on described benefits and risks, not actual treatment experience. GLP-1RAs are not approved for T1D, and the survey cannot assess clinical efficacy or safety in this population."},{"rthcId":"RPEP-08623","title":"Crafting Unnatural Peptide Macrocycles via Rh(III)-Catalyzed Carboamidation.","authors":"Lamartina, Christopher W; Chartier, Cassandra A; Hirano, Jillian M; Shah, Neel H; Rovis, Tomislav","year":2024,"journal":"Journal of the American Chemical Society, 146(30), 20868-20877","doi":"10.1021/jacs.4c05248","pmid":"39024122","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08624","title":"Efficacy and safety of galcanezumab as chronic cluster headache preventive treatment under real world conditions: Observational prospective study.","authors":"Lamas Pérez, Raquel; Millán-Vázquez, Manuel; González-Oria, Carmen","year":2024,"journal":"Cephalalgia : an international journal of headache, 44(3), 3331024231226181","doi":"10.1177/03331024231226181","pmid":"38501892","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08625","title":"Neuropeptide substance P attenuates colitis by suppressing inflammation and ferroptosis via the cGAS-STING signaling pathway.","authors":"Lan, Jing; Deng, Ziteng; Wang, Qiuzhen; Li, Dan; Fan, Kai; Chang, Jianyu; Ma, Yunfei","year":2024,"journal":"International journal of biological sciences, 20(7), 2507-2531","doi":"10.7150/ijbs.94548","pmid":"38725846","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08626","title":"The Anatomy, Histology, and Function of the Major Pelvic Ganglion.","authors":"Landa-García, Jessica Natalia; Palacios-Arellano, María de la Paz; Morales, Miguel Angel; Aranda-Abreu, Gonzalo Emiliano; Rojas-Durán, Fausto; Herrera-Covarrubias, Deissy; Toledo-Cárdenas, María Rebeca; Suárez-Medellín, Jorge Manuel; Coria-Avila, Genaro Alfonso; Manzo, Jorge; Hernández-Aguilar, Maria Elena","year":2024,"journal":"Animals : an open access journal from MDPI, 14(17)","doi":"10.3390/ani14172570","pmid":"39272355","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08627","title":"Detecting heart stress using NT-proBNP in patients with type 2 diabetes mellitus and hypertension or high-normal blood pressure: a cross-sectional multicentric study.","authors":"Landolfo, Matteo; Spannella, Francesco; Giulietti, Federico; Ortensi, Beatrice; Stella, Lucia; Carlucci, Maria A; Galeazzi, Roberta; Turchi, Federica; Luconi, Maria P; Zampa, Roberto; Cecchi, Sofia; Tortato, Elena; Petrelli, Massimiliano; Sarzani, Riccardo","year":2024,"journal":"Cardiovascular diabetology, 23(1), 297","doi":"10.1186/s12933-024-02391-z","pmid":"39135091","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08628","title":"Adrenergic Agonists Activate Transcriptional Activity in Immortalized Neuronal Cells From the Mouse Suprachiasmatic Nucleus.","authors":"Langiu, Monica; Dehghani, Faramarz; Hohmann, Urszula; Bechstein, Philipp; Rawashdeh, Oliver; Rami, Abdelhaq; Maronde, Erik","year":2024,"journal":"Journal of pineal research, 76(5), e12999","doi":"10.1111/jpi.12999","pmid":"39092782","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08629","title":"Antioxidant capacity and peptidomic analysis of in vitro digested Camelina sativa L. Crantz and Cynara cardunculus co-products.","authors":"Lanzoni, Davide; Grassi Scalvini, Francesca; Petrosillo, Elena; Nonnis, Simona; Tedeschi, Gabriella; Savoini, Giovanni; Buccioni, Arianna; Invernizzi, Guido; Baldi, Antonella; Giromini, Carlotta","year":2024,"journal":"Scientific reports, 14(1), 14456","doi":"10.1038/s41598-024-64989-3","pmid":"38914602","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08630","title":"Enzymatic hydrolysis of duck blood protein produces stable bioactive peptides: Pilot-scale production, identification, and stability during gastrointestinal and plasma digestion.","authors":"Laosam, Phanthipha; Luasiri, Pichitpon; Nakharuthai, Chatsirin; Boonanuntanasarn, Surintorn; Suwanangul, Saranya; Sarnthima, Rakrudee; Khammuang, Saranyu; Sanachai, Kamonpan; Yongsawadigul, Jirawat; Rouabhia, Mahmoud; Tastub, Sukanya; Sangsawad, Papungkorn","year":2024,"journal":"International journal of biological macromolecules, 283(Pt 3), 137864","doi":"10.1016/j.ijbiomac.2024.137864","pmid":"39566759","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08631","title":"Interactions of oral permeation enhancers with lipid membranes in simulated intestinal environments.","authors":"Larsen, Nanna Wichmann; Kostrikov, Serhii; Hansen, Morten Borre; Hjørringgaard, Claudia Ulrich; Larsen, Niels Bent; Andresen, Thomas Lars; Kristensen, Kasper","year":2024,"journal":"International journal of pharmaceutics, 654, 123957","doi":"10.1016/j.ijpharm.2024.123957","pmid":"38430950","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08632","title":"The therapeutic potential of bee venom-derived Apamin and Melittin conjugates in cancer treatment: A systematic review.","authors":"Laurindo, Lucas Fornari; de Lima, Enzo Pereira; Laurindo, Lívia Fornari; Rodrigues, Victória Dogani; Chagas, Eduardo Federighi Baisi; de Alvares Goulart, Ricardo; Araújo, Adriano Cressoni; Guiguer, Elen Landgraf; Pomini, Karina Torres; Rici, Rose Eli Grassi; Maria, Durvanei Augusto; Direito, Rosa; Barbalho, Sandra Maria","year":2024,"journal":"Pharmacological research, 209, 107430","doi":"10.1016/j.phrs.2024.107430","pmid":"39332751","tags":["antimicrobial-and-bioactive-peptides","peptide-drug-conjugates"],"studyType":"systematic-review","evidenceStrength":"low-moderate","keyFinding":"This systematic review examined preclinical studies on two bee venom peptides — melittin and apamin — when conjugated with other cancer drugs or loaded into novel delivery systems. Melittin-based conjugates, including PEGylated versions, showed improved tumor-targeting ability and reduced toxicity across multiple cancer models. Apamin-conjugated formulations enhanced the effectiveness of established anti-cancer drugs while reducing off-target side effects.\n\nThe review found that these peptide conjugates address two major problems in cancer treatment: drug resistance and collateral damage to healthy tissue. By using melittin or apamin as targeting or delivery vehicles, researchers were able to concentrate anti-cancer agents at tumor sites more effectively than the drugs alone.","whyItMatters":"Cancer drugs often fail because they can't reach tumors effectively or because cancer cells develop resistance. Bee venom peptides like melittin naturally disrupt cell membranes, which can be weaponized to selectively attack cancer cells. This review consolidates the preclinical evidence showing these peptides work as delivery enhancers and tumor-targeting agents — a fundamentally different approach from traditional chemotherapy.","specificNumbers":"Preclinical studies only · Multiple cancer models · PEGylated melittin conjugates tested · Apamin-drug conjugates tested · No clinical trial data yet","methodology":"Systematic review of preclinical studies examining apamin and melittin conjugates in cancer treatment. The authors followed systematic review methodology to identify, screen, and synthesize studies on bee venom-derived peptide conjugates and their anti-cancer properties across various tumor models.","limitations":"All included studies were preclinical — no human clinical trials have been conducted yet. The review covers multiple cancer types and conjugate formulations, making it difficult to draw conclusions about any single approach. Publication bias toward positive results is likely. The jump from preclinical promise to clinical reality remains unproven for these peptides."},{"rthcId":"RPEP-08633","title":"The Five-Year Incidence of Progression to Osteoarthritis and Total Joint Arthroplasty in Patients Prescribed Glucagon-Like Peptide 1 Receptor Agonists.","authors":"Lavu, Monish S; Porto, Joshua R; Hecht, Christian J; Kaelber, David C; Sculco, Peter K; Heckmann, Nathanael D; Kamath, Atul F","year":2024,"journal":"The Journal of arthroplasty, 39(10), 2433-2439.e1","doi":"10.1016/j.arth.2024.06.008","pmid":"38857711","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08634","title":"Efficacy, tolerability and pharmacokinetics of survodutide, a glucagon/glucagon-like peptide-1 receptor dual agonist, in cirrhosis.","authors":"Lawitz, Eric J; Fraessdorf, Mandy; Neff, Guy W; Schattenberg, Jörn M; Noureddin, Mazen; Alkhouri, Naim; Schmid, Bernhard; Andrews, Charles P; Takács, István; Hussain, Samina Ajaz; Fenske, Wiebke K; Gane, Edward J; Hosseini-Tabatabaei, Azadeh; Sanyal, Arun J; Mazo, Daniel F; Younes, Ramy","year":2024,"journal":"Journal of hepatology, 81(5), 837-846","doi":"10.1016/j.jhep.2024.06.003","pmid":"38857788","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08635","title":"Enhancing the Intrinsic Antiplasmodial Activity and Improving the Stability and Selectivity of a Tunable Peptide Scaffold Derived from Human Platelet Factor 4.","authors":"Lawrence, Nicole; Handley, Thomas N G; de Veer, Simon J; Harding, Maxim D; Andraszek, Alicja; Hall, Lachlan; Raven, Karoline D; Duffy, Sandra; Avery, Vicky M; Craik, David J; Malins, Lara R; McMorran, Brendan J","year":2024,"journal":"ACS infectious diseases, 10(8), 2899-2912","doi":"10.1021/acsinfecdis.4c00276","pmid":"39087267","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08636","title":"Early and annual projected savings from anti-CGRP monoclonal antibodies in migraine prevention: a cost-benefit analysis in the working-age population.","authors":"Lazaro-Hernandez, Carlos; Caronna, Edoardo; Rosell-Mirmi, Joana; Gallardo, Victor J; Alpuente, Alicia; Torres-Ferrus, Marta; Pozo-Rosich, Patricia","year":2024,"journal":"The journal of headache and pain, 25(1), 21","doi":"10.1186/s10194-024-01727-0","pmid":"38347485","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08637","title":"Glucagon and GLP-1 receptor dual agonist survodutide for obesity: a randomised, double-blind, placebo-controlled, dose-finding phase 2 trial.","authors":"le Roux, Carel W; Steen, Oren; Lucas, Kathryn J; Startseva, Elena; Unseld, Anna; Hennige, Anita M","year":2024,"journal":"The lancet. Diabetes & endocrinology, 12(3), 162-173","doi":"10.1016/S2213-8587(23)00356-X","pmid":"38330987","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Survodutide produced dose-dependent weight loss across all four dose groups over 46 weeks. Mean body weight changes from baseline were: -6.2% (0.6 mg), -12.5% (2.4 mg), -13.2% (3.6 mg), -14.9% (4.8 mg), compared to -2.8% with placebo.\n\nAdverse events occurred in 91% of survodutide recipients versus 75% of placebo recipients. Gastrointestinal side effects were the most common, affecting 75% of survodutide users compared to 42% on placebo. Despite this, all doses were considered tolerable. Of the 386 treated participants, 60.4% completed the full 46-week treatment period, with similar completion rates between survodutide (61%) and placebo (60%).","whyItMatters":"The obesity drug landscape has been dominated by GLP-1 receptor agonists like semaglutide, but dual agonists that also activate the glucagon receptor could offer additional weight loss by increasing the body's energy expenditure on top of appetite suppression. Survodutide's 14.9% weight loss is competitive with other leading obesity drugs and establishes dual agonism as a viable therapeutic strategy. This trial laid the groundwork for Phase 3 studies that could lead to FDA approval.","specificNumbers":"","methodology":"This was a randomized, double-blind, placebo-controlled, dose-finding Phase 2 trial conducted at 43 centers across 12 countries. Participants aged 18–75 with BMI ≥27 kg/m² and without diabetes were randomly assigned (1:1:1:1:1, stratified by sex) to receive weekly subcutaneous survodutide at 0.6, 2.4, 3.6, or 4.8 mg, or placebo for 46 weeks (20 weeks dose escalation, 26 weeks dose maintenance). The primary endpoint was percentage change in body weight from baseline to week 46. The trial was funded by Boehringer Ingelheim.","limitations":"As a Phase 2 dose-finding trial, the study was not powered for definitive efficacy conclusions. The 40% dropout rate over 46 weeks is notable, though similar to other obesity drug trials. Gastrointestinal side effects were frequent, and long-term safety beyond 46 weeks is unknown. The study excluded people with diabetes, so efficacy and safety in diabetic obesity populations is not established. The trial was funded by the drug manufacturer (Boehringer Ingelheim)."},{"rthcId":"RPEP-08638","title":"Dual-drug controllable co-assembly nanosystem for targeted and synergistic treatment of hepatocellular carcinoma.","authors":"Le, Jing-Qing; Song, Xun-Huan; Tong, Ling-Wu; Lin, Ying-Qi; Feng, Ke-Ke; Tu, Yi-Fan; Hu, Yong-Shan; Shao, Jing-Wei","year":2024,"journal":"Journal of colloid and interface science, 656, 177-188","doi":"10.1016/j.jcis.2023.11.109","pmid":"37989051","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08639","title":"The Impact of Glucagon-like Peptide 1 Receptor Agonists on Obstructive Sleep Apnoea: A Scoping Review.","authors":"Le, Khang Duy Ricky; Le, Kelvin; Foo, Felicia","year":2024,"journal":"Pharmacy (Basel, Switzerland), 12(1)","doi":"10.3390/pharmacy12010011","pmid":"38251405","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across nine included studies, there was early evidence suggesting GLP-1 receptor agonists may improve obstructive sleep apnea as measured by reductions in the apnoea-hypopnoea index (AHI). However, this finding was not consistent — some studies showed contradictory results.\n\nOf the nine articles, five were randomized clinical trials of variable quality, one was a non-randomized trial, one was a case report, one was a study protocol, and one was an RCT abstract. All studies examined GLP-1RA use in patients with diagnosed OSA or suggestive symptoms. The medications were generally well tolerated, with only minor gastrointestinal side effects reported.","whyItMatters":"Sleep apnea affects millions of people worldwide and is typically managed with CPAP machines, which many patients find uncomfortable and difficult to use consistently. If GLP-1 receptor agonists — already proven effective for weight loss and blood sugar control — could also treat sleep apnea, it would offer a more convenient pharmaceutical alternative. However, this review shows the science isn't there yet, tempering the market hype that has already driven major investment shifts away from traditional sleep apnea treatments.","specificNumbers":"","methodology":"The researchers conducted a scoping review by searching three major medical databases — Medline, Embase, and Cochrane Central. They included any papers that evaluated GLP-1 receptor agonist medications in relation to sleep-disordered breathing, obstructive sleep apnea, or related conditions. Nine articles met the inclusion criteria and were analyzed.","limitations":"The quality of evidence across all included studies was low. Follow-up periods were too short to assess whether any improvements in sleep apnea would be durable over time. The study pool was small at just nine articles, and the study designs varied widely — from case reports to randomized trials — making it difficult to draw strong conclusions. Results across studies were also conflicting, with some showing benefit and others not."},{"rthcId":"RPEP-08640","title":"S100A9 Exacerbates the Inflammation in Rosacea through Toll-Like Receptor 4/MyD88/NF-κB Signaling Pathway.","authors":"Le, Yan; Zhang, Jiawen; Lin, Yi; Ren, Jie; Xiang, Leihong; Zhang, Chengfeng","year":2024,"journal":"The Journal of investigative dermatology, 144(9), 1985-1993.e1","doi":"10.1016/j.jid.2024.02.012","pmid":"38447867","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08641","title":"Potential of Cell-Penetrating Peptide-Conjugated Antisense Oligonucleotides for the Treatment of SMA.","authors":"Leckie, Jamie; Yokota, Toshifumi","year":2024,"journal":"Molecules (Basel, Switzerland), 29(11)","doi":"10.3390/molecules29112658","pmid":"38893532","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08642","title":"Structural modifications toward improved lead-203/lead-212 peptide-based image-guided alpha-particle radiopharmaceutical therapies for neuroendocrine tumors.","authors":"Lee, Dongyoul; Li, Mengshi; Liu, Dijie; Baumhover, Nicholas J; Sagastume, Edwin A; Marks, Brenna M; Rastogi, Prerna; Pigge, F Christopher; Menda, Yusuf; Johnson, Frances L; Schultz, Michael K","year":2024,"journal":"European journal of nuclear medicine and molecular imaging, 51(4), 1147-1162","doi":"10.1007/s00259-023-06494-9","pmid":"37955792","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The modified radiopeptide [203Pb]Pb-PSC-PEG2-TOC showed significantly improved properties versus standard DOTATOC:\n\n- Better receptor binding and tumor accumulation/retention\n- Faster renal clearance (reduced kidney toxicity risk)\n- [212Pb]Pb-PSC-PEG2-TOC showed dose-dependent therapeutic effect with minimal toxicity\n- Fractionated administration (3 doses of 3.7 MBq) achieved:\n  - 80% overall survival at 120 days\n  - 70% complete response (tumor disappearance)\n  - Minimal signs of toxicity\n- Structural modifications to chelator (PSC) and linker (PEG2) drove the improvements","whyItMatters":"Neuroendocrine tumors are often treated with peptide receptor radionuclide therapy (PRRT) using beta-emitting isotopes, but alpha particles are more potent at killing cancer cells. This study demonstrates that structurally optimized octreotide peptides can effectively deliver alpha-emitting lead-212 to tumors, potentially providing more effective treatment than current beta-particle approaches for neuroendocrine cancers.","specificNumbers":"","methodology":"New SSTR2-targeted peptides were designed with a modified cyclization technique, lead-specific chelator (PSC), and PEG linkers. Binding affinity and cellular uptake were tested in AR42J pancreatic tumor cells (SSTR2+). Biodistribution and imaging were assessed in AR42J tumor xenograft mice using lead-203. Therapeutic efficacy was evaluated with lead-212 (alpha particle therapy) in the same mouse model, including dose-response and fractionated dosing studies.","limitations":"This was a preclinical study using a subcutaneous xenograft mouse model, which doesn't fully replicate human neuroendocrine tumors. The AR42J cell line may not represent the diversity of human NETs. Long-term toxicity of alpha particle therapy was not fully assessed. Translation to humans requires addressing differences in pharmacokinetics, radiation dosimetry, and tumor biology. Lead-212's 10.6-hour half-life presents manufacturing and logistics challenges."},{"rthcId":"RPEP-08643","title":"Effect of BPC-157 on Symptoms in Patients with Interstitial Cystitis: A Pilot Study.","authors":"Lee, Edwin; Walker, Christopher; Ayadi, Bahram","year":2024,"journal":"Alternative therapies in health and medicine, 30(10), 12-17","doi":null,"pmid":"39325560","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 12 women with moderate to severe interstitial cystitis who had failed pentosan polysulfate treatment, a single intravesical injection of BPC-157 (10 mg total) around the inflamed bladder area produced complete symptom resolution in 10 of 12 patients (100% success rating). The remaining 2 patients reported 80% improvement. All 12 scored 5/5 on the Global Response Assessment. No adverse events were reported, and no patients dropped out.","whyItMatters":"Interstitial cystitis (bladder pain syndrome) is a debilitating condition with very limited treatment options — the only approved drug (pentosan polysulfate) often fails and can cause eye damage with long-term use. This pilot study from Dr. Edwin Lee is notable as one of the few published human trials of BPC-157, and the results were striking: a single injection resolved symptoms in most patients who had already failed standard treatment.","specificNumbers":"12 patients; 10/12 complete resolution (100%); 2/12 rated 80% improvement; 12/12 scored 5/5 GRA; 10 mg BPC-157; mean age 58.3; 0 adverse events; 0 dropouts","methodology":"This was an open-label pilot study at a private clinic. Twelve women (aged 39-76, mean 58.3 years) with interstitial cystitis who had not responded to pentosan polysulfate underwent cystoscopy. During the procedure, BPC-157 (10 mg total, from a 503A compounding pharmacy) was injected around the area of bladder inflammation in a single treatment. Efficacy was assessed using the Global Response Assessment questionnaire.","limitations":"Very small sample size (12 patients). No placebo control or blinding — this was an open-label study, making placebo effects a significant concern. Single-site study at a private clinic. No long-term follow-up data reported. BPC-157 was sourced from a compounding pharmacy, not pharmaceutical-grade manufacturing. The journal (Alternative Therapies) is not a top-tier urology publication."},{"rthcId":"RPEP-08644","title":"Potential role of the cell-penetrating peptide-conjugated soluble N-ethylmaleimide-sensitive factor attachment protein receptor motif of vesicle-associated membrane protein 2-patterned peptide in novel cosmeceutical skin product development.","authors":"Lee, Hyo Jin; Kim, Daehoon; Choi, Hyo Jeong; Kim, Suhyeok; Shin, Minhee; Kwak, Seongsung; Lee, Dong-Kyu; Kang, Won-Ho","year":2024,"journal":"Journal of cosmetic dermatology, 23(2), 666-675","doi":"10.1111/jocd.15984","pmid":"37698157","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08645","title":"Identification of Structure-Linked Activity on Bioactive Peptides from Sea Cucumber (Stichopus japonicus): A Compressive In Silico/In Vitro Study.","authors":"Lee, Hyo-Geun; Nagahawatta, D P; Je, Jun-Geon; Oh, Jae-Young; Jayawardhana, H H A C K; Liyanage, N M; Kurera, M J M S; Park, Si-Hyeong; Jeon, You-Jin; Jung, Won-Kyo; Choe, Yu Ri; Kim, Hyun-Soo","year":2024,"journal":"Frontiers in bioscience (Landmark edition), 29(10), 368","doi":"10.31083/j.fbl2910368","pmid":"39473427","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08646","title":"Glucagon-Like Peptide Receptor Agonist Inhibits Angiotensin II-Induced Proliferation and Migration in Vascular Smooth Muscle Cells and Ameliorates Phosphate-Induced Vascular Smooth Muscle Cells Calcification.","authors":"Lee, Jinmi; Hong, Seok-Woo; Kim, Min-Jeong; Moon, Sun Joon; Kwon, Hyemi; Park, Se Eun; Rhee, Eun-Jung; Lee, Won-Young","year":2024,"journal":"Diabetes & metabolism journal, 48(1), 83-96","doi":"10.4093/dmj.2022.0363","pmid":"38173373","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08647","title":"Oxytocin decreases alcohol self-administration in male baboons.","authors":"Lee, Mary R; Moore, Catherine F; Weerts, Elise M","year":2024,"journal":"Translational psychiatry, 14(1), 369","doi":"10.1038/s41398-024-03076-7","pmid":"39261461","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08648","title":"Development of the novel amylin and calcitonin receptor activators by peptide mutagenesis.","authors":"Lee, Sangmin","year":2024,"journal":"Archives of biochemistry and biophysics, 762, 110191","doi":"10.1016/j.abb.2024.110191","pmid":"39481742","tags":["amylin","metabolic-peptides"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Researchers engineered novel peptide activators of both amylin and calcitonin receptors by systematically mutating rat amylin. By screening the C-terminal fragment of rat amylin for affinity-enhancing mutations, they identified up to twelve mutational combinations that increased binding affinity for both receptor types by over 100-fold.\n\nThree full-length (37 amino acid) rat amylin analogs incorporating these mutations were then tested for receptor activation potency. All three showed 5- to 10-fold greater potency than endogenous rat amylin and outperformed pramlintide, the only clinically approved amylin receptor activator currently used for diabetes management.","whyItMatters":"Amylin receptor activation in the brain controls blood glucose levels and suppresses appetite, making it a prime target for obesity and diabetes treatment. Current non-selective amylin/calcitonin receptor activators are already being tested for weight loss. This study produced peptide variants that significantly outperform pramlintide — the existing clinical amylin analog — suggesting that more potent next-generation amylin-based therapeutics are achievable through rational peptide design.","specificNumbers":"37-amino-acid peptide analogs · >100-fold affinity increase from mutations · 5-10x potency increase vs. endogenous rat amylin · outperformed pramlintide · 12 mutational combinations identified","methodology":"The researchers used comprehensive mutagenesis of rat amylin peptide, focusing on the C-terminal fragment that interacts with the amylin receptor extracellular domain. They screened mutational combinations for enhanced binding affinity to both amylin and calcitonin receptor extracellular domains. The most promising mutations were then incorporated into full-length 37-amino-acid rat amylin analogs and tested for receptor activation potency in cell-based assays (HEK293 cells).","limitations":"This is entirely an in vitro study using cell-based receptor activation assays — no animal or human testing was performed. The authors note these peptides are primarily useful as pharmacological tools for cell-based systems, not yet as drug candidates. Selectivity between amylin and calcitonin receptors was not a design goal, so off-target calcitonin effects are possible. Stability, pharmacokinetics, and in vivo efficacy remain untested."},{"rthcId":"RPEP-08649","title":"Glucagon-like peptide-1 receptor agonists (GLP-1RAs) as treatment for nicotine cessation in psychiatric populations: a systematic review.","authors":"Lee, Serene; Li, Maggie; Le, Gia Han; Teopiz, Kayla M; Vinberg, Maj; Ho, Roger; Au, Hezekiah C T; Wong, Sabrina; Valentino, Kyle; Kwan, Angela T H; Rosenblat, Joshua D; McIntyre, Roger S","year":2024,"journal":"Annals of general psychiatry, 23(1), 45","doi":"10.1186/s12991-024-00527-9","pmid":"39529123","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08650","title":"Semaglutide Ameliorates Diabetic Neuropathic Pain by Inhibiting Neuroinflammation in the Spinal Cord.","authors":"Lee, Sing-Ong; Kuthati, Yaswanth; Huang, Wei-Hsiu; Wong, Chih-Shung","year":2024,"journal":"Cells, 13(22)","doi":"10.3390/cells13221857","pmid":"39594606","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08651","title":"Antioxidative and Anti-Atopic Dermatitis Effects of Peptides Derived from Hydrolyzed Sebastes schlegelii Tail By-Products.","authors":"Lee, Sung-Gyu; Hwang, Jin-Woo; Kang, Hyun","year":2024,"journal":"Marine drugs, 22(10)","doi":"10.3390/md22100479","pmid":"39452887","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08652","title":"Improved prediction of anti-angiogenic peptides based on machine learning models and comprehensive features from peptide sequences.","authors":"Lee, Yun-Chen; Yu, Jen-Chieh; Ni, Kuan; Lin, Yu-Chuan; Chen, Ching-Tai","year":2024,"journal":"Scientific reports, 14(1), 14387","doi":"10.1038/s41598-024-65062-9","pmid":"38909149","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08653","title":"Distinct roles of the extracellular surface residues of glucagon-like peptide-1 receptor in β-arrestin 1/2 signaling.","authors":"Lei, Saifei; Meng, Qian; Liu, Yanyun; Liu, Qiaofeng; Dai, Antao; Cai, Xiaoqing; Wang, Ming-Wei; Zhou, Qingtong; Zhou, Hu; Yang, Dehua","year":2024,"journal":"European journal of pharmacology, 968, 176419","doi":"10.1016/j.ejphar.2024.176419","pmid":"38360293","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08654","title":"Comprehensive Evaluation of a Levonorgestrel Intrauterine Device (LNG-IUD), Metformin, and Liraglutide for Fertility Preservation in Endometrial Cancer: Protocol for a Randomized Clinical Trial.","authors":"Leipold, Gergő; Tóth, Richárd; Hársfalvi, Péter; Lőczi, Lotti; Török, Marianna; Keszthelyi, Attila; Ács, Nándor; Lintner, Balázs; Várbíró, Szabolcs; Keszthelyi, Márton","year":2024,"journal":"Life (Basel, Switzerland), 14(7)","doi":"10.3390/life14070835","pmid":"39063589","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"This is a clinical trial protocol (not yet completed). The study will randomize 264 obese women (BMI >30, aged 18-45) with endometrial hyperplasia or early-stage endometrial cancer into three groups:\n\n1. LNG-IUD alone (standard care)\n2. LNG-IUD + metformin\n3. LNG-IUD + metformin + liraglutide\n\nThe hypothesis is that the triple combination will achieve higher complete pathological remission rates than LNG-IUD alone, through both direct metabolic effects and weight loss that reduces estrogen-driven cancer growth. The 12-month trial will also track glucose, insulin levels, weight changes, and histological outcomes.","whyItMatters":"Endometrial cancer rates are rising as obesity increases globally. For young women who want children, current fertility-preserving options have limited success. Adding metabolic interventions like liraglutide could significantly improve remission rates by addressing the obesity-driven metabolic dysfunction that fuels this cancer.","specificNumbers":"","methodology":"Randomized clinical trial with three parallel arms. 264 women with BMI >30 and endometrial hyperplasia or early-stage endometrial cancer desiring uterine preservation will be enrolled. Primary outcome is complete pathological remission. Secondary outcomes include histological changes, metabolic markers, and weight changes over 12 months.","limitations":"This is a protocol publication — no results are available yet. The trial has not been completed or reported. Whether liraglutide's benefits are primarily from weight loss or direct anti-cancer effects won't be fully separable. The BMI >30 enrollment criterion limits generalizability to non-obese patients with endometrial cancer."},{"rthcId":"RPEP-08655","title":"Effects of the glucagon-like peptide-1 receptor agonist dulaglutide on sexuality in healthy men: a randomised, double-blind, placebo-controlled crossover study.","authors":"Lengsfeld, Sophia; Probst, Leila; Emara, Yara; Werlen, Laura; Vogt, Deborah R; Bathelt, Cemile; Baur, Fabienne; Caviezel, Brida; Vukajlovic, Tanja; Fischer, Manuel; Winzeler, Bettina","year":2024,"journal":"EBioMedicine, 107, 105284","doi":"10.1016/j.ebiom.2024.105284","pmid":"39232425","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08656","title":"Do relationships between ambient temperature and serious adverse health outcomes vary among users of different antidiabetes drugs? A retrospective cohort study of US Medicaid beneficiaries with type 2 diabetes.","authors":"Leonard, Charles E; Bogar, Kacie; Brensinger, Colleen M; Bilker, Warren B; Bell, Michelle L; Flory, James H; Shi, Christopher; Chen, Cheng; Hennessy, Sean","year":2024,"journal":"BMJ open, 14(10), e085139","doi":"10.1136/bmjopen-2024-085139","pmid":"39433419","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among over 713,000 users of specific diabetes drug classes:\n\n- Higher maximum daily temperatures were linearly associated with increased serious hypoglycemia among users of glimepiride and glyburide (sulfonylureas) but not glipizide (interaction p=0.048)\n- An inverse association was found between temperature and DKA among sitagliptin (DPP-4i) users (p=0.016) — less DKA in hotter weather\n- Exenatide (GLP-1RA) users showed no significant temperature-DKA association (p=0.080)\n- No drug class showed temperature-related changes in sudden cardiac arrest risk\n\nThe findings indicate drug-specific and even agent-specific differences in how ambient temperature affects glycemic safety outcomes.","whyItMatters":"As climate change increases extreme heat events, understanding how temperature interacts with common medications is crucial for patient safety. This is the first large study to examine temperature-drug interactions across multiple diabetes drug classes. The finding that certain sulfonylureas become more dangerous in heat — while GLP-1RAs and DPP-4 inhibitors appear safer — could inform prescribing decisions and heat safety guidelines for vulnerable populations.","specificNumbers":"","methodology":"Retrospective cohort study linking US Medicaid claims data with Department of Commerce meteorological data across five US states from 1999-2010. Approximately 3 million people with type 2 diabetes were followed at the person-day level. Maximum daily ambient temperature was assigned by residential ZIP code. Modified Poisson regression assessed relationships between temperature and outcomes (serious hypoglycemia, DKA, sudden cardiac arrest) among drug class subcohorts, with effect modification analysis.","limitations":"The study used data from 1999-2010, before newer GLP-1RAs (semaglutide, tirzepatide) were available. Exenatide was the only GLP-1RA assessed. The Medicaid population may not represent all diabetes patients. ZIP code-level temperature assignment is imprecise (doesn't account for indoor cooling or individual exposure). The observational design cannot establish causation. Confounders like physical activity, hydration, and adherence in heat may not be fully captured."},{"rthcId":"RPEP-08657","title":"Significance of host antimicrobial peptides in the pathogenesis and treatment of acne vulgaris.","authors":"Lesiak, Agata; Paprocka, Paulina; Wnorowska, Urszula; Mańkowska, Angelika; Król, Grzegorz; Głuszek, Katarzyna; Piktel, Ewelina; Spałek, Jakub; Okła, Sławomir; Fiedoruk, Krzysztof; Durnaś, Bonita; Bucki, Robert","year":2024,"journal":"Frontiers in immunology, 15, 1502242","doi":"10.3389/fimmu.2024.1502242","pmid":"39744637","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies several key roles of antimicrobial peptides in acne:\n\n- AMPs (human β-defensins, cathelicidin LL-37, dermcidin, RNase-7) are elevated in acne-affected skin\n- They function as both antibacterial agents and immune modulators, coordinating host-microbiota interactions\n- AMPs improve skin tight junction (TJ) barrier function by activating PI3K, GSK-3, aPKC, and Rac1 proteins\n- Elevated AMP expression likely represents a compensatory mechanism to protect skin with impaired permeability\n- AMPs link acne immune responses to metabolic signaling (insulin/IGF-1, PI3K/Akt/mTOR/FoxO1, glucotoxicity)\n- Acne is associated with decreased diversity of C. acnes phylotypes, with AMPs potentially regulating this dysbiosis","whyItMatters":"Antibiotic-resistant acne is a growing problem, and current treatments have significant side effects. Understanding how the skin's own antimicrobial peptides regulate acne could lead to entirely new treatment approaches that work with the body's natural defense systems rather than against bacteria directly. AMP-based therapies could potentially avoid the antibiotic resistance problem.","specificNumbers":"","methodology":"This is a comprehensive literature review incorporating recent transcriptomic studies, examining the role of antimicrobial peptides in acne pathogenesis. The review covers AMP expression patterns, their mechanisms of action in skin barrier maintenance and immune regulation, and the current state of AMP-based therapeutic development for acne.","limitations":"As a review article, no original data is presented. The hypothesis that AMPs act primarily as compensatory barrier protectors in acne is intriguing but requires further experimental validation. The complexity of acne pathogenesis (hormonal, genetic, microbial, immune) makes it difficult to isolate the specific contribution of AMPs. AMP-based acne therapeutics are still in early development stages."},{"rthcId":"RPEP-08658","title":"Differential Effects of GLP-1 Receptor Agonists on Cancer Risk in Obesity: A Nationwide Analysis of 1.1 Million Patients.","authors":"Levy, Shauna; Attia, Abdallah; Elshazli, Rami M; Abdelmaksoud, Ahmed; Tatum, Danielle; Aiash, Hani; Toraih, Eman A","year":2024,"journal":"Cancers, 17(1)","doi":"10.3390/cancers17010078","pmid":"39796706","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08659","title":"Hyperpolarized 13C and 31P MRS detects differences in cardiac energetics, metabolism, and function in obesity, and responses following treatment.","authors":"Lewis, Andrew J M; Dodd, Michael S; Sourdon, Joevin; Lygate, Craig A; Clarke, Kieran; Neubauer, Stefan; Tyler, Damian J; Rider, Oliver J","year":2024,"journal":"NMR in biomedicine, 37(11), e5206","doi":"10.1002/nbm.5206","pmid":"38994722","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08660","title":"Nanofibrous MultiDomain Peptide Hydrogels Provide T Cells a 3D, Cytocompatible Environment for Cell Expansion and Antigen-Specific Killing.","authors":"Leyva-Aranda, Viridiana; Singh, Shailbala; Telesforo, Maria J; Young, Simon; Yee, Cassian; Hartgerink, Jeffrey D","year":2024,"journal":"ACS biomaterials science & engineering, 10(3), 1448-1460","doi":"10.1021/acsbiomaterials.3c01617","pmid":"38385283","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08661","title":"The G Protein-First Mechanism for Activation of the Class B Glucagon-like Peptide 1 Receptor Coupled to N-Terminal Domain-Mediated Conformational Progression.","authors":"Li, Bo; Yang, Moon Young; Kim, Soo-Kyung; Goddard, William A","year":2024,"journal":"Journal of the American Chemical Society, 146(38), 26251-26260","doi":"10.1021/jacs.4c08128","pmid":"39266057","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08662","title":"TC-14, a cathelicidin-derived antimicrobial peptide with broad-spectrum antibacterial activity and high safety profile.","authors":"Li, Chenxi; Cai, Ying; Luo, Lin; Tian, Gengzhou; Wang, Xingyu; Yan, An; Wang, Liunan; Wu, Sijing; Wu, Zhongxiang; Zhang, Tianyu; Chen, Wenlin; Zhang, Zhiye","year":2024,"journal":"iScience, 27(7), 110404","doi":"10.1016/j.isci.2024.110404","pmid":"39092176","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"TC-14, a novel antimicrobial peptide engineered from a Chinese tree shrew cathelicidin (TC-33), exhibited a 432-fold increase in antimicrobial activity compared to the parent peptide. TC-14 adopts an amphipathic α-helical structure and kills bacteria by targeting and rupturing their membranes. Critically, TC-14 showed no cytotoxic or hemolytic activity, high biocompatibility in vivo, and provided significant protection in a mouse skin infection model — demonstrating both potency and safety.","whyItMatters":"Finding antimicrobial peptides that are both potent and safe has been the central challenge in AMP drug development. TC-14 achieves this rare combination — 432-fold more active than its parent peptide with zero toxicity to human cells and confirmed safety in animals. Its efficacy in a skin infection model makes it a promising candidate for treating bacterial infections, particularly topical infections where antibiotic resistance is growing.","specificNumbers":"432-fold increased activity vs parent TC-33 · amphipathic α-helix structure · no cytotoxicity · no hemolysis · safe in vivo · effective in murine skin infection model · broad-spectrum antibacterial","methodology":"TC-33 cathelicidin was identified from the Chinese tree shrew. TC-14 was designed from its active region and characterized structurally (revealing amphipathic α-helical conformation). Mechanism of action was studied through membrane permeabilization and rupture assays. Safety was assessed via cytotoxicity, hemolysis, and in vivo biocompatibility testing. Therapeutic efficacy was demonstrated in a mouse skin infection model.","limitations":"Only skin infection was tested in vivo; systemic infection models and intravenous administration were not evaluated. The spectrum of bacteria tested and specific MIC values were not detailed in the abstract. Long-term resistance development to TC-14 was not assessed. Manufacturing scalability and cost for a 14-amino-acid peptide drug need evaluation. The tree shrew-derived sequence may face regulatory novelty challenges."},{"rthcId":"RPEP-08663","title":"Research progress on the PEGylation of therapeutic proteins and peptides (TPPs).","authors":"Li, Chunxiao; Li, Ting; Tian, Xinya; An, Wei; Wang, Zhenlong; Han, Bing; Tao, Hui; Wang, Jinquan; Wang, Xiumin","year":2024,"journal":"Frontiers in pharmacology, 15, 1353626","doi":"10.3389/fphar.2024.1353626","pmid":"38523641","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08664","title":"Drug-Induced Acute Pancreatitis: A Real-World Pharmacovigilance Study Using the FDA Adverse Event Reporting System Database.","authors":"Li, Dongxuan; Wang, Hongli; Qin, Chunmeng; Du, Dan; Wang, Yalan; Du, Qian; Liu, Songqing","year":2024,"journal":"Clinical pharmacology and therapeutics, 115(3), 535-544","doi":"10.1002/cpt.3139","pmid":"38069538","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08665","title":"A 3D radially aligned nanofiber scaffold co-loaded with LL37 mimetic peptide and PDGF-BB for the management of infected chronic wounds.","authors":"Li, Fei; Zhang, Chuwei; Zhong, Xiaoping; Li, Bo; Zhang, Mengnan; Li, Wanqian; Zheng, Lifei; Zhu, Xinghua; Chen, Shixuan; Zhang, Yi","year":2024,"journal":"Materials today. Bio, 28, 101237","doi":"10.1016/j.mtbio.2024.101237","pmid":"39315393","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08666","title":"The fusion protein of scorpion neurotoxin BjαIT and Galanthus nivalis agglutinin (GNA) enhanced the injection insecticidal activity against silkworms, but only has lethal activity against newly hatched larva when administered orally.","authors":"Li, Hongbo; Tian, Cheng; Chen, Jing; Xia, Yuanxian","year":2024,"journal":"World journal of microbiology & biotechnology, 40(10), 326","doi":"10.1007/s11274-024-04140-6","pmid":"39299979","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08667","title":"Acid-Activated TAT Peptide-Modified Biomimetic Boron Nitride Nanoparticles for Enhanced Targeted Codelivery of Doxorubicin and Indocyanine Green: A Synergistic Cancer Photothermal and Chemotherapeutic Approach.","authors":"Li, Hui; Fan, Yuan; Shen, Yizhe; Xu, Huashan; Zhang, Huijie; Chen, Fuxue; Feng, Shini","year":2024,"journal":"ACS applied materials & interfaces, 16(19), 25101-25112","doi":"10.1021/acsami.4c01622","pmid":"38691046","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08668","title":"CycPeptMP: enhancing membrane permeability prediction of cyclic peptides with multi-level molecular features and data augmentation.","authors":"Li, Jianan; Yanagisawa, Keisuke; Akiyama, Yutaka","year":2024,"journal":"Briefings in bioinformatics, 25(5)","doi":"10.1093/bib/bbae417","pmid":"39210505","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08669","title":"A novel ACE inhibitory peptide from Douchi hydrolysate: Stability, inhibition mechanism, and antihypertensive potential in spontaneously hypertensive rats.","authors":"Li, Jianfei; Hu, Haohan; Chen, Xiya; Zhu, Haiting; Zhang, Wenhao; Tai, Zhiyuan; Yu, Xiaodong; He, Qiyi","year":2024,"journal":"Food chemistry, 460(Pt 3), 140734","doi":"10.1016/j.foodchem.2024.140734","pmid":"39106751","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"From Douchi hydrolysate, five ACE inhibitory peptides were identified: LF, VVF, VGAW, GLFG, and NGK. The tetrapeptide VGAW was the most potent:\n\n- ACE inhibition IC50: 46.6 ± 5.2 µM (competitive inhibitor)\n- Excellent thermal and pH stability\n- Molecular docking revealed 8 hydrogen bonds between VGAW and ACE\n- Lineweaver-Burk plots confirmed competitive inhibition mechanism\n- Significantly reduced blood pressure in spontaneously hypertensive rats at 12.5, 25, and 50 mg/kg doses\n\nThe optimal enzyme combination for generating these peptides was pepsin-trypsin-chymotrypsin, outperforming 10 single enzymes and 3 other combinations.","whyItMatters":"Finding effective blood pressure-lowering peptides in a traditional food product like Douchi validates centuries of dietary wisdom with modern science. Food-derived ACE inhibitory peptides could offer a natural, side-effect-free approach to blood pressure management as functional food ingredients or supplements.","specificNumbers":"","methodology":"Ten single enzymes and four combinations were tested for Douchi hydrolysis. Hydrolysates were purified using Sephadex G-15 gel filtration and reversed-phase HPLC. Peptides were identified via LC-MS/MS. ACE inhibition was measured with IC50 values and Lineweaver-Burk kinetic analysis. Molecular docking simulated peptide-ACE interactions. In vivo antihypertensive activity was tested in spontaneously hypertensive rats at three dose levels.","limitations":"The in vivo testing was done in spontaneously hypertensive rats, which may not fully represent human hypertension. The oral bioavailability of VGAW in humans is unknown — it may be degraded during human digestion despite showing enzyme stability in lab tests. No human clinical trials were conducted. The amount of VGAW naturally present in Douchi versus what was isolated through intensive hydrolysis may differ significantly."},{"rthcId":"RPEP-08670","title":"Characterization, mechanisms, structure-activity relationships, and antihypertensive effects of ACE inhibitory peptides: rapid screening from sufu hydrolysate.","authors":"Li, Jianfei; Hu, Haohan; Chen, Feng; Yang, Chenying; Yang, Wanzhou; Pan, Yuexin; Yu, Xiaodong; He, Qiyi","year":2024,"journal":"Food & function, 15(18), 9224-9234","doi":"10.1039/d4fo02834a","pmid":"39158526","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08671","title":"Structural basis for activation of somatostatin receptor 5 by cyclic neuropeptide agonists.","authors":"Li, Jingru; You, Chongzhao; Li, Yang; Li, Changyao; Fan, Wenjia; Chen, Zecai; Hu, Wen; Wu, Kai; Xu, H Eric; Zhao, Li-Hua","year":2024,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 121(26), e2321710121","doi":"10.1073/pnas.2321710121","pmid":"38885377","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08672","title":"Efficacy and safety of semaglutide combined with metformin in treating T2DM with overweight or obesity: a systematic review and meta-analysis.","authors":"Li, Juan; Li, Kui; Liu, Zhaoyun; Yu, Huiwen; Zhang, Jie","year":2024,"journal":"American journal of translational research, 16(8), 3545-3556","doi":"10.62347/RYLN5360","pmid":"39262717","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08673","title":"Molecular Mechanism of P53 Peptide Permeation through Lipid Membranes from Solid-State NMR Spectroscopy and Molecular Dynamics Simulations.","authors":"Li, Mingyue; Li, Jianguo; Lu, Xingyu; Schroder, Ryan; Chandramohan, Arun; Wuelfing, W Peter; Templeton, Allen C; Xu, Wei; Gindy, Marian; Kesisoglou, Filippos; Ling, Jing; Sawyer, Tomi; Verma, Chandra S; Partridge, Anthony W; Su, Yongchao","year":2024,"journal":"Journal of the American Chemical Society, 146(33), 23075-23091","doi":"10.1021/jacs.4c04230","pmid":"39110018","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08674","title":"Liraglutide ameliorates TAC-induced cardiac hypertrophy and heart failure by upregulating expression level of ANP expression.","authors":"Li, Ruisha; Zhang, Keyin; Xu, Zhenjun; Yu, Yanrong; Wang, Dongjin; Li, Kai; Liu, Wenxue; Pan, Jun","year":2024,"journal":"Heliyon, 10(11), e32229","doi":"10.1016/j.heliyon.2024.e32229","pmid":"38868006","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08675","title":"Lacticaseibacillus paracasei NCU-04 relieves constipation and the depressive-like behaviors induced by loperamide in mice through the microbiome-gut-brain axis.","authors":"Li, Shengjie; Li, Yi; Cai, Yujie; Yan, Zizhou; Wei, Jing; Zhang, Hongyan; Yue, Fenfang; Chen, Tingtao","year":2024,"journal":"Current research in food science, 9, 100875","doi":"10.1016/j.crfs.2024.100875","pmid":"39429918","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08676","title":"Membrane-Active All-Hydrocarbon-Stapled α-Helical Amphiphilic Tat Peptides: Broad-Spectrum Antibacterial Activity and Low Incidence of Drug Resistance.","authors":"Li, Shu; Wang, Zhaopeng; Song, Shibo; Tang, Yuanyuan; Zhou, Jingjing; Liu, Xiaojing; Zhang, Xingjiao; Chang, Min; Wang, Kairong; Peng, Yali","year":2024,"journal":"ACS infectious diseases, 10(5), 1839-1855","doi":"10.1021/acsinfecdis.4c00173","pmid":"38725407","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08677","title":"Formyl peptide receptor 1 mitigates colon inflammation and maintains mucosal homeostasis through the inhibition of CREB-C/EBPβ-S100a8 signaling.","authors":"Li, Tingting; Zhou, Xiaojun; Zhang, Qian; Miao, Qi; Woodman, Owen L; Chen, Yuguo; Qin, Chengxue","year":2024,"journal":"Mucosal immunology, 17(4), 651-672","doi":"10.1016/j.mucimm.2024.04.001","pmid":"38614323","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08678","title":"In Vitro Study of Thymosin Beta 4 Promoting Transplanted Fat Survival by Regulating Adipose-Derived Stem Cells.","authors":"Li, Wandi; Yang, Yan; Lin, Yan; Mu, Dali","year":2024,"journal":"Aesthetic plastic surgery, 48(11), 2179-2189","doi":"10.1007/s00266-024-03861-1","pmid":"38409346","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08679","title":"Antimicrobial neuropeptides and their therapeutic potential in vertebrate brain infectious disease.","authors":"Li, Xiaoke; Chen, Kaiqi; Liu, Ruonan; Zheng, Zhaodi; Hou, Xitan","year":2024,"journal":"Frontiers in immunology, 15, 1496147","doi":"10.3389/fimmu.2024.1496147","pmid":"39620214","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08680","title":"Effects of Glucagon-Like Peptide-1 Receptor Agonists on Bone Metabolism in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.","authors":"Li, Xin; Li, Yang; Lei, Chen","year":2024,"journal":"International journal of endocrinology, 2024, 1785321","doi":"10.1155/2024/1785321","pmid":"39309475","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08681","title":"Two Novel Angiotensin-Converting Enzyme (ACE) Inhibitory and ACE2 Upregulating Peptides from the Hydrolysate of Pumpkin (Cucurbita moschata) Seed Meal.","authors":"Li, Xin; Peng, Chenghai; Xiao, Suyao; Wang, Qun; Zhou, Aimei","year":2024,"journal":"Journal of agricultural and food chemistry, 72(19), 10909-10922","doi":"10.1021/acs.jafc.4c00609","pmid":"38689562","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Two peptides were identified with ACE inhibitory activity: SNHANQLDFHP (IC₅₀ = 172.07 μM) and PVQVLASAYR (IC₅₀ = 90.69 μM). Molecular docking showed both interact with ACE through hydrogen bonds and hydrophobic interactions.\n\nIn endothelial cells (EA.hy926), both peptides decreased endothelin-1 secretion (a vasoconstrictor), increased nitric oxide release (a vasodilator), and upregulated ACE2 activity (the protective arm of the renin-angiotensin system). Both peptides showed good stability against simulated gastrointestinal enzyme digestion, supporting potential oral bioavailability.","whyItMatters":"Pumpkin seed meal is currently a waste product of the oil industry. Discovering that it contains bioactive peptides with multiple blood pressure-lowering mechanisms — ACE inhibition, ACE2 upregulation, and direct vascular protection — could add significant value to this agricultural byproduct while providing natural alternatives or supplements for hypertension management.","specificNumbers":"","methodology":"Pumpkin seed meal hydrolysate was prepared using Neutrase 5.0 BG enzyme. Peptides were isolated and purified through ultrafiltration, Sephadex G-15 chromatography, and RP-HPLC. ACE inhibition was measured in vitro. Molecular docking modeled peptide-ACE interactions. Endothelial cell assays measured endothelin-1, nitric oxide, and ACE2 activity. Simulated gastrointestinal digestion tested stability.","limitations":"All findings are from in vitro experiments and computational modeling — no animal or human studies have confirmed blood pressure-lowering effects. The IC₅₀ values are higher than pharmaceutical ACE inhibitors, so clinical significance is uncertain. Simulated digestion may not fully represent in vivo conditions. Actual oral bioavailability in living organisms was not measured."},{"rthcId":"RPEP-08682","title":"Alleviation of migraine related pain and anxiety by inhibiting calcium-stimulating AC1-dependent CGRP in the insula of adult rats.","authors":"Li, Yang; Li, Chenhao; Chen, Qi-Yu; Hao, Shun; Mao, Jingrui; Zhang, Wenwen; Han, Xun; Dong, Zhao; Liu, Ruozhuo; Tang, Wenjing; Zhuo, Min; Yu, Shengyuan; Liu, Yinglu","year":2024,"journal":"The journal of headache and pain, 25(1), 81","doi":"10.1186/s10194-024-01778-3","pmid":"38760739","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08683","title":"Mitochondrial-derived peptides in cardiovascular disease: Novel insights and therapeutic opportunities.","authors":"Li, Yang; Li, Zhuozhuo; Ren, Yuanyuan; Lei, Ying; Yang, Silong; Shi, Yuqi; Peng, Han; Yang, Weijie; Guo, Tiantian; Yu, Yi; Xiong, Yuyan","year":2024,"journal":"Journal of advanced research, 64, 99-115","doi":"10.1016/j.jare.2023.11.018","pmid":"38008175","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08684","title":"Molecular mechanism of prolactin-releasing peptide recognition and signaling via its G protein-coupled receptor.","authors":"Li, Yang; Yuan, Qingning; He, Xinheng; Zhang, Yumu; You, Chongzhao; Wu, Canrong; Li, Jingru; Xu, H Eric; Zhao, Li-Hua","year":2024,"journal":"Cell discovery, 10(1), 91","doi":"10.1038/s41421-024-00724-6","pmid":"39223120","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08685","title":"The effect of subcutaneous dulaglutide on weight loss in patients with Type 2 diabetes mellitus: Systematic review and meta-analysis of randomized controlled trials.","authors":"Li, Yang; Gong, Xingji; Găman, Mihnea-Alexandru; Hernández-Wolters, Benjamin; Velu, Periyannan; Li, Yushan","year":2024,"journal":"European journal of clinical investigation, 54(4), e14125","doi":"10.1111/eci.14125","pmid":"37950521","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08686","title":"Association of semaglutide treatment with coronary artery inflammation in type 2 diabetes mellitus patients: a retrospective study based on pericoronary adipose tissue attenuation.","authors":"Li, Yanhong; Yao, Wenjing; Wang, Tianxing; Yang, Qian; Song, Kexin; Zhang, Feifei; Wang, Fan; Dang, Yi","year":2024,"journal":"Cardiovascular diabetology, 23(1), 348","doi":"10.1186/s12933-024-02445-2","pmid":"39342279","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08687","title":"Sodium glycocholate liposome encapsulated semaglutide increases oral bioavailability by promoting intestinal absorption.","authors":"Li, Yehan; Liu, Fei; Che, Jiajing; Zhang, Yu; Yin, Tian; Gou, Jingxin; Tang, Xing; Wang, Yanjiao; He, Haibing","year":2024,"journal":"International journal of pharmaceutics, 665, 124669","doi":"10.1016/j.ijpharm.2024.124669","pmid":"39244070","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08688","title":"Structural insights into somatostatin receptor 5 bound with cyclic peptides.","authors":"Li, Ying-Ge; Meng, Xian-Yu; Yang, Xiru; Ling, Sheng-Long; Shi, Pan; Tian, Chang-Lin; Yang, Fan","year":2024,"journal":"Acta pharmacologica Sinica, 45(11), 2432-2440","doi":"10.1038/s41401-024-01314-8","pmid":"38926478","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Two cryo-EM structures were solved: SSTR5-Gi complex with pasireotide at 3.09Å resolution and SSTR5-Gi complex with octreotide at 3.24Å resolution. Structural analysis revealed that pasireotide's preferential binding to SSTR5 is mediated by interactions between its Tyr(Bzl) and DTrp residues and specific SSTR5 binding pocket features.\n\nFor octreotide's bias toward SSTR2, key residues were identified: Q2.63, N6.55, F7.35, and extracellular loop 2 (ECL2) of SSTR2 play crucial roles. These findings explain the molecular basis of peptide-receptor selectivity and provide specific structural targets for designing more selective SSTR5-targeted drugs.","whyItMatters":"Pasireotide is the only FDA-approved drug for Cushing's disease, but its side effects (especially hyperglycemia) limit its use. Understanding exactly how it binds SSTR5 at the atomic level enables rational design of next-generation somatostatin analogs with improved selectivity — drugs that target SSTR5 precisely without activating SSTR2 and causing metabolic side effects. This is structure-based drug design at its most impactful.","specificNumbers":"","methodology":"Cryo-electron microscopy was used to determine the 3D structures of SSTR5-Gi signaling complexes bound to pasireotide and octreotide. Structural analysis identified key binding interactions and selectivity determinants. Functional experiments validated the structural observations and tested the importance of specific residues for receptor activation and selectivity.","limitations":"Cryo-EM structures capture a static snapshot of receptor-peptide interactions and may not fully represent the dynamic binding process. The structures were determined using purified receptor-Gi complexes, which may not perfectly replicate the cellular membrane environment. Functional validation was performed in cell lines (HEK293), not in disease-relevant pituitary tumor cells. The structural insights need to be translated into actual drug candidates and tested for improved selectivity in pharmacological studies."},{"rthcId":"RPEP-08689","title":"Liraglutide Ameliorates Renal Endothelial Dysfunction in Diabetic Rats Through the Inhibition of the Dll4/Notch2 Pathway.","authors":"Li, Yining; Chen, Yulin; Zhang, Hui; Chen, Weidong; Pan, Yan","year":2024,"journal":"Diabetes, metabolic syndrome and obesity : targets and therapy, 17, 4091-4104","doi":"10.2147/DMSO.S492252","pmid":"39492960","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In a streptozotocin/high-fat diet diabetic rat model, liraglutide treatment produced dose-dependent improvements:\n\n- Significant reductions in blood glucose, serum creatinine, and blood urea nitrogen (P < 0.05)\n- Dose-dependent decrease in 24-hour urinary protein excretion and microalbuminuria (P < 0.05)\n- Improved glomerular and interstitial damage\n- Suppressed expression of endothelial injury markers CD31, CD34, and VE-cadherin (P < 0.05)\n- Significantly increased nitric oxide (NO) production (P < 0.05)\n- Decreased expression of VEGF, Dll4, and Notch2 protein in the Notch2 signaling pathway (P < 0.05)\n- Higher doses showed more pronounced therapeutic effects","whyItMatters":"Diabetic kidney disease is the leading cause of kidney failure worldwide. Understanding how GLP-1 drugs protect kidney blood vessels at the molecular level — specifically through the Dll4/Notch2 pathway — could help develop more targeted treatments and identify patients who would benefit most from GLP-1 therapy for kidney protection.","specificNumbers":"","methodology":"Diabetes was induced in rats using a high-fat/high-sugar diet combined with a single streptozotocin injection. Diabetic rats were treated with various doses of liraglutide. Kidney function was assessed by blood glucose, serum creatinine, BUN, and urinary protein. Kidney pathology was examined histologically. Endothelial markers (CD31, CD34, VE-cadherin), nitric oxide levels, and Dll4/Notch2 pathway proteins were measured.","limitations":"This was an animal study using a chemically-induced diabetes model, which may not fully replicate human diabetic kidney disease. The specific doses may not correspond to human therapeutic levels. The study focused on early endothelial dysfunction, so effects on advanced kidney disease are unknown. The Dll4/Notch2 pathway involvement is correlational — additional studies are needed to confirm it as the primary mechanism."},{"rthcId":"RPEP-08690","title":"Osteopontine-derived functional fragments coupled to RADA16 self-assembled peptide hydrogels promotes bone and vascular regeneration in vivo.","authors":"Li, Yong; Tang, Yao; Chen, LiFu; Li, HaiTao; Wang, Hong; Wang, Jian","year":2024,"journal":"Journal of biomaterials science. Polymer edition, 35(5), 657-674","doi":"10.1080/09205063.2024.2304951","pmid":"38284324","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The RADA16-OPD peptide hydrogel (RADA16 coupled with the osteopontin-derived fragment SVVYGLR) demonstrated superior bone regeneration in a rat skull defect model compared to RADA16 alone or untreated controls. Micro-CT analysis showed higher bone volume/total volume (BV/TV), higher trabecular number (TB.N.), and higher bone mineral density (BMD) at multiple time points.\n\nHistological analysis confirmed more new bone formation and mature collagen production in the RADA16-OPD group. Expression of osteogenic markers alkaline phosphatase (ALP) and osteocalcin (OCN) were elevated. Additionally, immunofluorescence showed significantly higher CD31 (platelet/endothelial cell adhesion molecule) expression, indicating enhanced blood vessel formation. Live/dead staining confirmed the scaffold was non-toxic to rat adipose-derived stem cells (rASCs).","whyItMatters":"Large bone defects from trauma, surgery, or disease often can't heal on their own. Current options like bone grafts have significant limitations — donor site pain, limited supply, and infection risk. A self-assembling peptide scaffold that can be injected as a liquid and form a gel in place, while simultaneously promoting both bone growth and blood vessel formation, could revolutionize bone repair. The peptide-based approach offers advantages in biocompatibility, biodegradability, and ease of manufacturing.","specificNumbers":"","methodology":"Researchers designed RADA16-OPD by linking the SVVYGLR peptide to the C-terminus of the self-assembling RADA16 peptide. Scaffold structure was characterized by atomic force microscopy. Biocompatibility was tested using live/dead staining with rat adipose-derived stem cells. For in vivo testing, rat skull defect models were created and treated with RADA16-OPD hydrogel, RADA16 alone, or left untreated. Outcomes were assessed using micro-CT (bone volume, trabecular structure, density), histology (bone formation, collagen maturity), and immunostaining for osteogenic markers (ALP, OCN) and vascular marker (CD31).","limitations":"This is a preclinical rat study, and bone healing in rats is significantly faster and more robust than in humans. The rat skull defect model, while standard, may not reflect the mechanical loading environment of weight-bearing bones where scaffolds would be most clinically needed. Long-term degradation and mechanical properties of the scaffold were not assessed. The study did not compare RADA16-OPD to clinical gold-standard treatments like autologous bone grafting. Specific defect size and group numbers are not detailed in the abstract."},{"rthcId":"RPEP-08691","title":"Intervertebral disc injury triggers neurogenic inflammation of adjacent healthy discs.","authors":"Li, Yongchao; Dai, Chen; Wu, Bing; Yang, Liang; Yan, Xiujie; Liu, Tanghua; Chen, Jindong; Zheng, Zhaomin; Peng, Baogan","year":2024,"journal":"The spine journal : official journal of the North American Spine Society, 24(8), 1527-1537","doi":"10.1016/j.spinee.2024.04.002","pmid":"38608821","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08692","title":"Therapeutic stapled peptides: Efficacy and molecular targets.","authors":"Li, Yulei; Wu, Minghao; Fu, Yinxue; Xue, Jingwen; Yuan, Fei; Qu, Tianci; Rissanou, Anastassia N; Wang, Yilin; Li, Xiang; Hu, Honggang","year":2024,"journal":"Pharmacological research, 203, 107137","doi":"10.1016/j.phrs.2024.107137","pmid":"38522761","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08693","title":"Hesperidin facilitating gastrointestinal motility by \"Gut-brain axis\" and \"SCF/C-Kit signaling pathways\".","authors":"Li, Yunfei; Zhou, Xinying; Du, Yusong; An, Mingyuan; Wan, Shasha; Sun, Zewei; Zhong, Qingzhen","year":2024,"journal":"Poultry science, 103(12), 104390","doi":"10.1016/j.psj.2024.104390","pmid":"39437558","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08694","title":"Deciphering the Wound-Healing Potential of Collagen Peptides and the Molecular Mechanisms: A Review.","authors":"Li, Yunying; Lu, Yujia; Zhao, Yuchen; Zhang, Na; Zhang, Yuhao; Fu, Yu","year":2024,"journal":"Journal of agricultural and food chemistry, 72(47), 26007-26026","doi":"10.1021/acs.jafc.4c02960","pmid":"39405278","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08695","title":"A Stapled Peptide Inhibitor Targeting the Binding Interface of N6-Adenosine-Methyltransferase Subunits METTL3 and METTL14 for Cancer Therapy.","authors":"Li, Zenghui; Feng, Yuqing; Han, Hong; Jiang, Xingyue; Chen, Weiyu; Ma, Xuezhen; Mei, Yang; Yuan, Dan; Zhang, Dingxiao; Shi, Junfeng","year":2024,"journal":"Angewandte Chemie (International ed. in English), 63(24), e202402611","doi":"10.1002/anie.202402611","pmid":"38607929","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"From candidate peptides screened against the METTL3-METTL14 binding interface, RM3 showed the highest anti-cancer potency by both inhibiting METTL3 activity and promoting its proteasomal degradation. The stapled version (RSM3) had enhanced stability and maintained the α-helical structure needed for METTL3 interaction.\n\nIn two in vivo tumor models, RSM3 treatment significantly suppressed tumor growth and enhanced apoptosis. Mechanistically, RSM3 increased METTL3 degradation, reduced global RNA m6A methylation levels, upregulated programmed cell death genes, and inhibited cancer-promoting signaling pathways. This dual mechanism — complex disruption plus protein degradation — distinguishes it from competitive small-molecule inhibitors.","whyItMatters":"METTL3 is increasingly recognized as an oncogene across multiple cancer types, but therapeutic options targeting it are limited. This study introduces a fundamentally different approach — using a stapled peptide to disrupt a protein-protein interaction rather than competing at the enzyme's active site. The dual mechanism of enzyme inhibition plus degradation could provide more complete suppression of METTL3 activity.","specificNumbers":"","methodology":"Researchers designed peptides targeting the METTL3-METTL14 protein-protein interaction interface. The lead peptide RM3 was optimized into a stapled version (RSM3) for improved stability and helical structure. Activity was assessed through in vitro enzyme inhibition assays, cell-based cancer models, and transcriptomic analysis. In vivo efficacy was tested in two mouse tumor models, with measurements of tumor growth, apoptosis, METTL3 protein levels, and global RNA methylation.","limitations":"The study was conducted in cell lines and mouse tumor models, which may not fully predict human responses. Pharmacokinetics, biodistribution, and potential off-target effects of RSM3 in humans are unknown. The specific cancer types tested were not detailed in the abstract, and generalizability to other METTL3-driven cancers needs investigation. Long-term safety of disrupting RNA methylation was not assessed."},{"rthcId":"RPEP-08696","title":"Preparation and Vasodilation Mechanism of Angiotensin-I-Converting Enzyme Inhibitory Peptide from Ulva prolifera Protein.","authors":"Li, Zhiyong; He, Hongyan; Liu, Jiasi; Gu, Huiyue; Fu, Caiwei; Zeb, Aurang; Che, Tuanjie; Shen, Songdong","year":2024,"journal":"Marine drugs, 22(9)","doi":"10.3390/md22090398","pmid":"39330279","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08697","title":"The C-terminal self-binding helical peptide of human estrogen-related receptor γ can be druggably targeted by a novel class of rationally designed peptidic antagonists.","authors":"Li, Zilong; Peng, Yue; Ye, Haiyang; Zhang, Yunyi; Zhou, Peng","year":2024,"journal":"Journal of computational chemistry, 45(32), 2771-2777","doi":"10.1002/jcc.27473","pmid":"39158951","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08698","title":"Evaluation of the antitumor effect of neoantigen peptide vaccines derived from the translatome of lung cancer.","authors":"Lian, Fenbao; Yang, Haitao; Hong, Rujun; Xu, Hang; Yu, Tingting; Sun, Gang; Zheng, Guanying; Xie, Baosong","year":2024,"journal":"Cancer immunology, immunotherapy : CII, 73(7), 129","doi":"10.1007/s00262-024-03670-0","pmid":"38744688","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08699","title":"Systematical mutational analysis of teriparatide on anti-osteoporosis activity by alanine scanning.","authors":"Liang, Haiyan; Shen, Huaxing; Zheng, Mengjun; Shi, Yejiao; Li, Xiang","year":2024,"journal":"Bioorganic & medicinal chemistry letters, 104, 129732","doi":"10.1016/j.bmcl.2024.129732","pmid":"38583785","tags":["teriparatide","osteoporosis","peptide-engineering"],"studyType":"Basic Science (Peptide Chemistry)","evidenceStrength":"Preliminary","keyFinding":"Researchers systematically replaced each amino acid in teriparatide (the first FDA-approved bone-building osteoporosis drug) with alanine, one position at a time, to map which residues are essential for its anti-osteoporosis activity. They synthesized and tested 34 teriparatide derivatives.\n\nFive residues proved critical: replacing Gly12, His14, Ser17, Arg20, or Leu24 with alanine dramatically reduced activity — these positions are essential for teriparatide's bone-building function. Conversely, replacing Gly13 or Gln30 with alanine actually increased activity, suggesting these positions are candidates for modification to create more potent next-generation osteoporosis peptides.","whyItMatters":"Teriparatide (Forteo) is effective at building new bone but has side effects and a 2-year usage limit. Understanding exactly which parts of the peptide drive its activity — and which can be changed — is essential for designing improved versions. This study provides a complete residue-by-residue map that peptide drug designers can use to create more potent analogs with potentially fewer side effects or longer treatment windows.","specificNumbers":"34 derivatives synthesized · 5 critical residues (Gly12, His14, Ser17, Arg20, Leu24) · 2 improvable positions (Gly13, Gln30) · alanine scanning of all positions","methodology":"Systematic alanine scanning mutagenesis of teriparatide (PTH 1-34). Each of the 34 amino acid positions was individually replaced with alanine, the resulting peptides were synthesized, and their anti-osteoporosis biological activities were evaluated. This is a standard structure-activity relationship (SAR) approach used in peptide drug development.","limitations":"The biological activity assays are not described in detail in the abstract — it's unclear whether testing was in cell-based assays, animal models, or both. Alanine scanning identifies important residues but doesn't reveal what other substitutions might be beneficial at each position. The study focuses on anti-osteoporosis activity but doesn't assess other properties like receptor binding affinity, pharmacokinetics, or in vivo bone mineral density changes. Only single-position mutations were tested — combinations might reveal synergistic improvements."},{"rthcId":"RPEP-08700","title":"Simultaneous ischemic regions targeting and BBB crossing strategy to harness extracellular vesicles for therapeutic delivery in ischemic stroke.","authors":"Liang, Huai-Bin; Chen, Xiao; Zhao, Rong; Li, Shen-Jie; Huang, Pei-Sheng; Tang, Yao-Hui; Cui, Guo-Hong; Liu, Jian-Ren","year":2024,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 365, 1037-1057","doi":"10.1016/j.jconrel.2023.12.021","pmid":"38109946","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08701","title":"Correlation between intestinal flora and GLP-1 receptor agonist dulaglutide in type 2 diabetes mellitus treatment-A preliminary longitudinal study.","authors":"Liang, Lei; Su, XiaoYun; Guan, Yaxin; Wu, Bin; Zhang, Xuxiang; Nian, Xin","year":2024,"journal":"iScience, 27(5), 109784","doi":"10.1016/j.isci.2024.109784","pmid":"38711446","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"After 48 weeks of dulaglutide administration, the composition of intestinal flora changed significantly in newly diagnosed T2DM patients, with a notable reduction in overall bacterial abundance. No significant changes were observed after just 1 week of treatment.\n\nFasting glucose levels, fasting C-peptide levels, HbA1c levels, and BMI were all found to be closely associated with changes in intestinal flora composition, suggesting that gut microbiome modulation may be one of the mechanisms through which dulaglutide treats type 2 diabetes.","whyItMatters":"GLP-1 receptor agonists like dulaglutide are among the most widely prescribed diabetes drugs, and understanding all the ways they work is important for optimizing treatment. This study suggests that beyond their known effects on insulin and blood sugar, these drugs may also work partly by reshaping the gut microbiome — opening up new avenues for understanding and improving diabetes treatment.","specificNumbers":"","methodology":"Researchers used 16S rRNA amplicon sequencing — a DNA-based technique for identifying bacterial species — to analyze stool samples from newly diagnosed type 2 diabetes patients. Samples were collected before treatment, after 1 week, and after 48 weeks of dulaglutide administration. The team then correlated microbiome changes with metabolic markers including fasting glucose, C-peptide, HbA1c, and BMI.","limitations":"This was a preliminary study with a relatively small sample size of newly diagnosed patients only. The study used 16S rRNA sequencing, which identifies bacteria at a broad level but may miss functional details. It was a longitudinal observational design, so it cannot prove that dulaglutide directly caused the microbiome changes — other factors like diet changes during treatment could contribute. No control group receiving placebo was mentioned."},{"rthcId":"RPEP-08702","title":"Real-world study of adverse events associated with gepant use in migraine treatment based on the VigiAccess and U.S. Food and Drug Administration's adverse event reporting system databases.","authors":"Liang, Qiaofang; Liao, Xiaolin; Wu, Hongwen; Huang, Yushen; Liang, Taolin; Li, Hailong","year":2024,"journal":"Frontiers in pharmacology, 15, 1431562","doi":"10.3389/fphar.2024.1431562","pmid":"39144633","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08703","title":"Research on the Synergistic Inhibition of Angiotensin-Converting Enzyme (ACE) by the Gastrointestinal Digestion Products of the ACE Inhibitory Peptide FPPDVA.","authors":"Liang, Yan; Zu, Xin-Yu; Zhao, Ya-Nan; Li, Ying-Qiu; Wang, Chen-Ying; Zhao, Xiang-Zhong; Wang, Hua","year":2024,"journal":"Journal of agricultural and food chemistry, 72(44), 24463-24475","doi":"10.1021/acs.jafc.4c05518","pmid":"39436688","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08704","title":"Association of incretin-based therapies with hepatobiliary disorders among patients with type 2 diabetes: a case series from the FDA adverse event reporting system.","authors":"Liang, Yankun; Zhang, Zhenpo; Zheng, Jingping; Wang, Yuting; He, Jiaxin; Zhao, Juanzhi; Su, Ling","year":2024,"journal":"Endocrine connections, 13(12)","doi":"10.1530/EC-24-0404","pmid":"39404734","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 68,351 incretin therapy case reports in FAERS, 1,327 (1.94%) involved hepatobiliary adverse events, with a pooled reporting odds ratio of 2.85 indicating a positive correlation.\n\nDPP-4 inhibitors showed statistically significant associations with cholelithiasis (gallstones), chronic cholecystitis, and biliary diseases. GLP-1 receptor agonists showed weaker overall associations but were linked to gallbladder/biliary disorders and had higher acute cholecystitis risk. Among specific drugs, liraglutide and semaglutide showed stronger positive correlations among GLP-1 agonists, while sitagliptin, linagliptin, and vildagliptin stood out among DPP-4 inhibitors. The associations may be dose-dependent.","whyItMatters":"As GLP-1 receptor agonists and DPP-4 inhibitors are prescribed to millions of people worldwide for diabetes (and increasingly for weight loss), understanding their safety profile is critical. This large-scale analysis identifies hepatobiliary events as a potential concern — particularly gallbladder problems — that clinicians should monitor for, especially in patients with pre-existing gallbladder risk factors.","specificNumbers":"","methodology":"This pharmacovigilance study extracted case reports involving incretin therapies and hepatobiliary adverse events from the FDA Adverse Event Reporting System (FAERS) spanning January 2006 to December 2023. Associations were analyzed using reporting odds ratios and empirical Bayesian geometric means. Descriptive analyses characterized demographic and clinical features. Subgroup analyses evaluated specific drug-event associations.","limitations":"FAERS is a spontaneous reporting system subject to reporting bias, underreporting, and the inability to establish causation. Reporting odds ratios cannot account for confounding factors like obesity, rapid weight loss, and diabetes itself — all of which are independent risk factors for gallbladder disease. The study cannot determine incidence rates or absolute risk. Duplicate reports may exist in FAERS data. The Weber effect (increased reporting for newer drugs) could inflate associations for more recently approved agents."},{"rthcId":"RPEP-08705","title":"Conjugation of sulpiride with a cell penetrating peptide to augment the antidepressant efficacy and reduce serum prolactin levels.","authors":"Liang, Yuan; Yang, Yu; Huang, Ruiyan; Ning, Jiangyue; Bao, Xingyan; Yan, Zelong; Chen, Haotian; Ding, Li; Shu, Chang","year":2024,"journal":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 174, 116610","doi":"10.1016/j.biopha.2024.116610","pmid":"38642503","tags":["drug-delivery","cell-penetrating-peptides"],"studyType":"animal-study","evidenceStrength":"early-research","keyFinding":"Linking the antidepressant drug sulpiride to a cell-penetrating peptide (VPALR, derived from the DNA repair protein Ku70) created a conjugate (VPALR-SUL) that crossed the blood-brain barrier more effectively than sulpiride alone. In depressed mice, VPALR-SUL significantly improved two key depression measures — increased struggle time and total distance — compared to sulpiride alone.\n\nCritically, the conjugate also reduced serum prolactin levels — addressing a major side effect of sulpiride. The drug normally can't reach the brain's pituitary gland well enough to suppress prolactin release, causing hyperprolactinemia (elevated prolactin with side effects like sexual dysfunction and breast changes). Pharmacokinetic data showed VPALR-SUL had a longer half-life and better bioavailability than sulpiride alone.","whyItMatters":"The blood-brain barrier blocks many promising psychiatric drugs from reaching their targets in the brain. Cell-penetrating peptides offer a biological solution — acting as molecular delivery vehicles that carry drugs across this barrier. This study demonstrates the concept with a real clinical problem: sulpiride works for depression but causes troublesome prolactin side effects precisely because it can't cross the BBB efficiently. By attaching a CPP, researchers simultaneously improved efficacy and reduced a key side effect — a double win that could apply to many other brain-targeted drugs.","specificNumbers":"VPALR peptide (from Ku70 protein) · Increased struggle time + total distance in depressed mice · Reduced serum prolactin vs sulpiride alone · Prolonged half-life · Increased bioavailability","methodology":"Researchers covalently linked sulpiride to the cell-penetrating peptide VPALR. The conjugate was tested in a mouse model of depression using intraperitoneal injection. Depression-related behaviors (struggle time, total distance) were measured. Serum prolactin levels were compared between VPALR-SUL and sulpiride-only groups. Pharmacokinetic studies assessed half-life and bioavailability of the conjugate.","limitations":"This is an animal study in mice — behavioral measures of depression in mice don't perfectly translate to human depression. The specific mechanism by which VPALR-SUL crosses the BBB better was not fully characterized. Long-term safety of the peptide-drug conjugate is unknown. The VPALR peptide itself may have immunogenic potential in humans. Manufacturing complexity of peptide-drug conjugates could limit clinical development."},{"rthcId":"RPEP-08706","title":"Clinical Evidence for GLP-1 Receptor Agonists in Alzheimer's Disease: A Systematic Review.","authors":"Liang, Yulin; Doré, Vincent; Rowe, Christopher C; Krishnadas, Natasha","year":2024,"journal":"Journal of Alzheimer's disease reports, 8(1), 777-789","doi":"10.3233/ADR-230181","pmid":"38746639","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"From 1,444 screened studies, six met inclusion criteria (four RCTs and two protocols). Two RCTs measuring amyloid-beta and tau biomarkers found no difference between GLP-1 RA and placebo groups at end of treatment. Three RCTs with cognitive endpoints also showed no improvement in treated groups. However, GLP-1 drugs provided metabolic benefits including lower BMI and improved glucose tolerance, and may mitigate decline in cerebral glucose metabolism as assessed by 18F-FDG PET imaging, with enhanced blood-brain glucose transport capacity.","whyItMatters":"There has been enormous excitement about repurposing GLP-1 drugs for Alzheimer's disease, driven by strong preclinical data and epidemiological associations. This review provides a sobering reality check: the clinical evidence so far does not support direct effects on core Alzheimer's pathology or cognition. However, the metabolic and cerebral glucose metabolism findings keep the door open — brain energy metabolism dysfunction is increasingly recognized as an early event in Alzheimer's, and GLP-1 drugs may address this aspect even if they can't reverse amyloid plaques or tau tangles.","specificNumbers":"","methodology":"Systematic review following standard methodology, searching PubMed, Embase, and Cochrane Library using MeSH terms and entry terms for GLP-1 receptor agonists and Alzheimer's disease. Specific drug names searched included liraglutide, exenatide, and lixisenatide. Of 1,444 screened studies, six articles met inclusion criteria.","limitations":"Only six studies met inclusion criteria, and the included RCTs were generally small with relatively short durations. Only older GLP-1 drugs (liraglutide, exenatide, lixisenatide) were tested — newer, more potent agents like semaglutide were not represented. The studies may have been too short to detect slow disease-modifying effects. The review was limited to AD-specific clinical trials and did not capture epidemiological data suggesting reduced AD risk in GLP-1 drug users."},{"rthcId":"RPEP-08707","title":"Free fatty acids: independent predictors of long-term adverse cardiovascular outcomes in heart failure patients.","authors":"Liao, Guang-Zhi; Liu, Hui-Hui; He, Chun-Hui; Feng, Jia-Yu; Zhuang, Xiao-Feng; Wang, Jing-Xi; Zhou, Ping; Huang, Yan; Zhou, Qiong; Zhai, Mei; Zhang, Yu-Hui; Zhang, Jian","year":2024,"journal":"Lipids in health and disease, 23(1), 343","doi":"10.1186/s12944-024-02332-5","pmid":"39438940","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 4,109 HF patients (median follow-up 25 months, max 8 years), FFA levels above 0.4-0.42 mmol/L were associated with increased risk of all three outcomes. Patients in the highest FFA tertile had significantly elevated risks versus the lowest tertile:\n- CV death & HF hospitalization: HR 1.32 (95% CI: 1.11-1.58)\n- CV death alone: HR 1.45 (95% CI: 1.16-1.82)\n- All-cause mortality: HR 1.39 (95% CI: 1.15-1.68)\n\nThese associations were consistent across HF subtypes (HFpEF and HFmrEF/HFrEF). Combining FFA with the natriuretic peptide biomarker NT-proBNP significantly improved the C-index for predicting outcomes compared to NT-proBNP alone (P < 0.01).","whyItMatters":"NT-proBNP is the most widely used peptide biomarker in cardiology, but its predictive power has limitations. This study shows that adding a simple, inexpensive metabolic marker (FFA) to NT-proBNP significantly improves risk stratification in heart failure. For peptide biomarker science, this demonstrates that natriuretic peptides work best as part of multi-marker panels rather than in isolation.","specificNumbers":"","methodology":"Prospective cohort study of 4,109 heart failure patients. Plasma FFA was analyzed as continuous and categorical (tertiles) variables. Cox regression models assessed associations with three outcomes: composite CV death and HF hospitalization, CV death alone, and all-cause mortality. Subgroup analyses by ejection fraction. C-index calculated for the combination of FFA and NT-proBNP versus NT-proBNP alone.","limitations":"This is an observational cohort study and cannot establish causation between elevated FFA and worse outcomes. The study population was from a single center, which may limit generalizability. FFA levels were measured at a single timepoint and may fluctuate with fasting status, diet, and medications. The study did not assess whether lowering FFA levels (e.g., through GLP-1 agonist treatment) improves outcomes."},{"rthcId":"RPEP-08708","title":"Peptides for Targeting Chondrogenic Induction and Cartilage Regeneration in Osteoarthritis.","authors":"Liao, Hsiu-Jung; Chen, Hui-Ting; Chang, Chih-Hung","year":2024,"journal":"Cartilage, 19476035241276406","doi":"10.1177/19476035241276406","pmid":"39291443","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08709","title":"A novel ACE inhibitory peptide from Pelodiscus sinensis Wiegmann meat water-soluble protein hydrolysate.","authors":"Liao, Pengying; Liu, Huayu; Sun, Xueqin; Zhang, Xinrui; Zhang, Miao; Wang, Xianyou; Chen, Jun","year":2024,"journal":"Amino acids, 56(1), 40","doi":"10.1007/s00726-024-03399-1","pmid":"38847939","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08710","title":"Lactoferricin B Combined with Antibiotics Exhibits Leukemic Selectivity and Antimicrobial Activity.","authors":"Lica, Jan Jakub; Gucwa, Katarzyna; Heldt, Mateusz; Stupak, Anna; Maciejewska, Natalia; Ptaszyńska, Natalia; Łęgowska, Anna; Pradhan, Bhaskar; Gitlin-Domagalska, Agata; Dębowski, Dawid; Jakóbkiewicz-Banecka, Joanna; Rolka, Krzysztof","year":2024,"journal":"Molecules (Basel, Switzerland), 29(3)","doi":"10.3390/molecules29030678","pmid":"38338422","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08711","title":"Modification of Mesenchymal Stem/Stromal Cell-Derived Small Extracellular Vesicles by Calcitonin Gene Related Peptide (CGRP) Antagonist: Potential Implications for Inflammation and Pain Reversal.","authors":"Liebmann, Kevin; Castillo, Mario A; Jergova, Stanislava; Best, Thomas M; Sagen, Jacqueline; Kouroupis, Dimitrios","year":2024,"journal":"Cells, 13(6)","doi":"10.3390/cells13060484","pmid":"38534328","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08712","title":"Nature-inspired peptide of MtDef4 C-terminus tail enables protein delivery in mammalian cells.","authors":"Lifshits, Lucia Adriana; Breuer, Yoav; Sova, Marina; Gupta, Sumit; Kadosh, Dar; Weinberg, Evgeny; Hayouka, Zvi; Bar, Daniel Z; Gal, Maayan","year":2024,"journal":"Scientific reports, 14(1), 4604","doi":"10.1038/s41598-024-55274-4","pmid":"38409451","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08713","title":"Disassembly of self-assembling peptide hydrogels as a versatile method for cell extraction and manipulation.","authors":"Ligorio, Cosimo; Martinez-Espuga, Magda; Laurenza, Domenico; Hartley, Alex; Rodgers, Chloe B; Kotowska, Anna M; Scurr, David J; Dalby, Matthew J; Ordóñez-Morán, Paloma; Mata, Alvaro","year":2024,"journal":"Journal of materials chemistry. B, 12(46), 11939-11952","doi":"10.1039/d4tb01575d","pmid":"39449374","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08714","title":"Glucagon-like peptide-1 analogs activate AMP kinase leading to reversal of the Warburg metabolic switch in breast cancer cells.","authors":"Ligumsky, Hagai; Amir, Sharon; Arbel Rubinstein, Tamar; Guion, Kate; Scherf, Tali; Karasik, Avraham; Wolf, Ido; Rubinek, Tami","year":2024,"journal":"Medical oncology (Northwood, London, England), 41(6), 138","doi":"10.1007/s12032-024-02390-w","pmid":"38705935","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08715","title":"Design and synthesis of peptides as stabilizers of histone deacetylase 4.","authors":"Lill, Annika; Schweipert, Markus; Nehls, Thomas; Wurster, Eva; Lermyte, Frederik; Meyer-Almes, Franz-Josef; Schmitz, Katja","year":2024,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 30(9), e3603","doi":"10.1002/psc.3603","pmid":"38623824","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08716","title":"LL37 Microspheres Loaded on Activated Carbon-chitosan Hydrogel: Anti-bacterial and Anti-toxin Wound Dressing for Chronic Wound Infections.","authors":"Lim, Bee-Yee; Azmi, Fazren; Ng, Shiow-Fern","year":2024,"journal":"AAPS PharmSciTech, 25(5), 110","doi":"10.1208/s12249-024-02826-6","pmid":"38740721","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The LL37-activated carbon-chitosan (LL37-AC-CS) hydrogel demonstrated effectiveness against three clinically important bacteria: Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. The hydrogel bound more endotoxin than activated carbon with chitosan hydrogel alone, indicating synergistic toxin-neutralizing capacity. The dressing induced cell migration after 72 hours (promoting wound closure) and showed no cytotoxicity toward normal human dermal fibroblasts (NHDF) after 72 hours of treatment.\n\nThe microsphere encapsulation strategy successfully protected LL37 from degradation in wound fluid, maintaining its antimicrobial activity in an environment where the free peptide would normally lose effectiveness.","whyItMatters":"Chronic wound infections are a major healthcare burden, and antibiotic resistance is making them harder to treat. LL37 has no known bacterial resistance, making it an attractive alternative, but it degrades quickly in wound environments. This delivery system solves that problem while adding toxin-neutralizing capability — addressing both the bacteria and the harmful substances they release when they die.","specificNumbers":"","methodology":"LL37 was encapsulated in microspheres, which were loaded onto an activated carbon-chitosan hydrogel. The formulation was characterized for physicochemical properties, drug release kinetics, and peptide-polymer compatibility. Antimicrobial activity was tested against E. coli, P. aeruginosa, and S. aureus. Antibiofilm activity, endotoxin binding capacity, cell migration assays, and cytotoxicity testing with normal human dermal fibroblasts were performed.","limitations":"This was entirely an in vitro study — no animal or human wound healing trials were conducted. The activated carbon component's long-term effects in wounds are unknown. The study did not assess performance in actual wound fluid or against polymicrobial biofilms typical of chronic wounds. Manufacturing scalability and cost were not addressed."},{"rthcId":"RPEP-08717","title":"Therapy for HFpEF: A step forward brings new hope for people with obesity and diabetes.","authors":"Lim, Lee-Ling; Khunti, Kamlesh","year":2024,"journal":"Med (New York, N.Y.), 5(8), 848-851","doi":"10.1016/j.medj.2024.06.011","pmid":"39127032","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08718","title":"CREB-regulated transcription during glycogen synthesis in astrocytes.","authors":"Lim, Wei Lee; Gaunt, Jessica Ruth; Tan, Jia Min; Zainolabidin, Norliyana; Bansal, Vibhavari Aysha; Lye, Yi Ming; Ch'ng, Toh Hean","year":2024,"journal":"Scientific reports, 14(1), 17942","doi":"10.1038/s41598-024-67976-w","pmid":"39095513","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"VIP-induced glycogen synthesis in astrocytes requires CREB-mediated transcription that is calcium-dependent and requires conventional Protein Kinase C (PKC) but not Protein Kinase A (PKA). VIP also triggers nuclear accumulation of the CREB coactivator CRTC2 in astrocytic nuclei.\n\nTranscriptomic profiling of VIP-stimulated astrocytes identified robust CREB transcription, including genes linked to glucose and glycogen metabolism. VIP-induced and glucose-induced glycogen synthesis share some molecular signatures but also have distinct features, though both require CREB-mediated transcription.","whyItMatters":"Brain energy metabolism is fundamental to cognition, and astrocyte glycogen is essential for memory formation. VIP is a neuropeptide that orchestrates this energy replenishment, and understanding its signaling pathway reveals how the brain manages its energy supply at the molecular level. Disruptions in this pathway could contribute to cognitive impairment and neurodegenerative conditions.","specificNumbers":"","methodology":"Researchers used cultured astrocytes stimulated with VIP to study the molecular signaling cascade leading to glycogen synthesis. They employed CREB activity assays, calcium imaging, pharmacological inhibitors of PKC and PKA, nuclear translocation studies of CRTC2, and transcriptomic profiling to identify VIP-induced gene expression changes. Results were compared with glucose-induced glycogen synthesis pathways.","limitations":"This is an in vitro study using cultured astrocytes, which may not fully replicate the complex cell interactions in the living brain. The transcriptomic profiling identifies candidate genes but doesn't confirm their functional roles in glycogen synthesis. The signaling pathway was characterized using pharmacological inhibitors, which can have off-target effects. In vivo validation of the VIP-CREB-glycogen pathway is needed."},{"rthcId":"RPEP-08719","title":"Molecular Modeling of Single- and Double-Hydrocarbon-Stapled Coiled-Coil Inhibitors against Bcr-Abl: Toward a Treatment Strategy for CML.","authors":"Lima, Maria Carolina P; Hornsby, Braxten D; Lim, Carol S; Cheatham, Thomas E","year":2024,"journal":"The journal of physical chemistry. B, 128(27), 6476-6491","doi":"10.1021/acs.jpcb.4c02699","pmid":"38951498","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08720","title":"Advanced Noninvasive Strategies for the Brain Delivery of Therapeutic Proteins and Peptides.","authors":"Lin, Jiayuan; Yu, Zhihua; Gao, Xiaoling","year":2024,"journal":"ACS nano, 18(34), 22752-22779","doi":"10.1021/acsnano.4c06851","pmid":"39133564","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08721","title":"Analgesic and anti-inflammatory effects of galangin: a potential pathway to inhibit transient receptor potential vanilloid 1 receptor activation.","authors":"Lin, Kaiwen; Fu, Datian; Wang, Zhongtao; Zhang, Xueer; Zhu, Canyang","year":2024,"journal":"The Korean journal of pain, 37(2), 151-163","doi":"10.3344/kjp.23363","pmid":"38557656","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08722","title":"Solid-Phase-Supported Chemoenzymatic Synthesis and Analysis of Chondroitin Sulfate Proteoglycan Glycopeptides.","authors":"Lin, Po-Han; Xu, Yongmei; Bali, Semiha Kevser; Kim, Jandi; Gimeno, Ana; Roberts, Elijah T; James, Deepak; Almeida, Nuno M S; Loganathan, Narasimhan; Fan, Fei; Wilson, Angela K; Jonathan Amster, I; Moremen, Kelley W; Liu, Jian; Jiménez-Barbero, Jesús; Huang, Xuefei","year":2024,"journal":"Angewandte Chemie (International ed. in English), 63(34), e202405671","doi":"10.1002/anie.202405671","pmid":"38781001","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08723","title":"GLP-1 receptor agonist liraglutide alleviates kidney injury by regulating nuclear translocation of NRF2 in diabetic nephropathy.","authors":"Lin, Tingting; Zhang, Yuze; Wei, Qifeng; Huang, Zugui","year":2024,"journal":"Clinical and experimental pharmacology & physiology, 51(12), e70003","doi":"10.1111/1440-1681.70003","pmid":"39477212","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08724","title":"Study on the Predictive Value of a Pulmonary Edema Imaging Score for Delayed Extubation in Patients after Heart Valve Surgery on Cardiopulmonary Bypass.","authors":"Lin, Xuefeng; Wang, Funan; Wang, Yuting","year":2024,"journal":"Reviews in cardiovascular medicine, 25(10), 387","doi":"10.31083/j.rcm2510387","pmid":"39484127","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08725","title":"Integrating Reinforcement Learning and Monte Carlo Tree Search for enhanced neoantigen vaccine design.","authors":"Lin, Yicheng; Ma, Jiakang; Yuan, Haozhe; Chen, Ziqiang; Xu, Xingyu; Jiang, Mengping; Zhu, Jialiang; Meng, Weida; Qiu, Wenqing; Liu, Yun","year":2024,"journal":"Briefings in bioinformatics, 25(3)","doi":"10.1093/bib/bbae247","pmid":"38770719","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08726","title":"Design and Self-Assembly of Peptide-Copolymer Conjugates into Nanoparticle Hydrogel for Wound Healing in Diabetes.","authors":"Lin, Yiling; Zhang, Yingneng; Cai, Xia; He, Huashen; Yang, Chuangzan; Ban, Junfeng; Guo, Bohong","year":2024,"journal":"International journal of nanomedicine, 19, 2487-2506","doi":"10.2147/IJN.S452915","pmid":"38486937","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08727","title":"Glucagon-like peptide receptor-1 receptor agonists: The emerging fourth pillar in type 2 diabetes and chronic kidney disease?","authors":"Ling, James; Chow, Elaine","year":2024,"journal":"Med (New York, N.Y.), 5(8), 845-847","doi":"10.1016/j.medj.2024.06.010","pmid":"39127031","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08728","title":"Optimising a self-assembling peptide hydrogel as a Matrigel alternative for 3-dimensional mammary epithelial cell culture.","authors":"Lingard, Eliana; Dong, Siyuan; Hoyle, Anna; Appleton, Ellen; Hales, Alis; Skaria, Eldhose; Lawless, Craig; Taylor-Hearn, Isobel; Saadati, Simon; Chu, Qixun; Miller, Aline F; Domingos, Marco; Saiani, Alberto; Swift, Joe; Gilmore, Andrew P","year":2024,"journal":"Biomaterials advances, 160, 213847","doi":"10.1016/j.bioadv.2024.213847","pmid":"38657288","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08729","title":"Semaglutide and Cardiovascular Outcomes by Baseline HbA1c and Change in HbA1c in People With Overweight or Obesity but Without Diabetes in SELECT.","authors":"Lingvay, Ildiko; Deanfield, John; Kahn, Steven E; Weeke, Peter E; Toplak, Hermann; Scirica, Benjamin M; Rydén, Lars; Rathor, Naveen; Plutzky, Jorge; Morales, Cristobal; Lincoff, A Michael; Lehrke, Michael; Jeppesen, Ole Kleist; Gajos, Grzegorz; Colhoun, Helen M; Cariou, Bertrand; Ryan, Donna","year":2024,"journal":"Diabetes care, 47(8), 1360-1369","doi":"10.2337/dc24-0764","pmid":"38907684","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08730","title":"Efficacy and Safety of Rimegepant 75 mg Oral Tablet, a CGRP Receptor Antagonist, for the Acute Treatment of Migraine: A Randomized, Double-Blind, Placebo-Controlled Trial.","authors":"Lipton, Richard B; Thiry, Alexandra; Morris, Beth A; Croop, Robert","year":2024,"journal":"Journal of pain research, 17, 2431-2441","doi":"10.2147/JPR.S453806","pmid":"39070853","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08731","title":"Preventive Treatment of Migraine.","authors":"Lipton, Richard B","year":2024,"journal":"Continuum (Minneapolis, Minn.), 30(2), 364-378","doi":"10.1212/CON.0000000000001418","pmid":"38568488","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Six drugs targeting CGRP are now approved for preventive treatment of episodic migraine in adults: four monoclonal antibodies (eptinezumab, erenumab, fremanezumab, galcanezumab) and two gepants (rimegepant, atogepant). The monoclonal antibodies and atogepant have demonstrated effectiveness for both episodic and chronic migraine. All CGRP-targeted therapies show favorable safety and tolerability profiles.\n\nThese therapies have enabled new paradigms for migraine prevention, moving beyond older drugs that were repurposed from other conditions toward purpose-built treatments designed specifically around the CGRP peptide pathway.","whyItMatters":"Migraine affects over 1 billion people globally and was historically treated with preventive medications borrowed from other conditions (blood pressure drugs, antidepressants, anti-seizure medications) that often had significant side effects. CGRP-targeted therapies represent the first class of medications designed specifically for migraine, targeting the peptide pathway now known to play a central role in migraine pathophysiology.","specificNumbers":"","methodology":"This is a clinical review article published in Continuum, a continuing medical education journal of the American Academy of Neurology. It synthesizes clinical trial evidence and clinical experience with CGRP-targeted therapies for migraine prevention, providing a comprehensive overview for practicing neurologists.","limitations":"As a review article, this does not present new primary data. The article focuses primarily on CGRP-targeted therapies and may not provide equal coverage of all available preventive migraine treatments. Long-term safety data beyond a few years is still accumulating for these relatively new medications. Cost and access remain barriers for many patients."},{"rthcId":"RPEP-08732","title":"Sustained response to atogepant in episodic migraine: post hoc analyses of a 12-week randomized trial and a 52-week long-term safety trial.","authors":"Lipton, Richard B; Nahas, Stephanie J; Pozo-Rosich, Patricia; Bilchik, Tanya; McAllister, Peter; Finnegan, Michelle; Liu, Yingyi; Chalermpalanupap, Natty; Dabruzzo, Brett; Dodick, David W","year":2024,"journal":"The journal of headache and pain, 25(1), 83","doi":"10.1186/s10194-024-01783-6","pmid":"38773375","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08733","title":"Shorter-acting glucagon-like peptide-1 receptor agonists are associated with increased development of gastro-oesophageal reflux disease and its complications in patients with type 2 diabetes mellitus: a population-level retrospective matched cohort study.","authors":"Liu, Benjamin Douglas; Udemba, Sharon C; Liang, Katherine; Tarabichi, Yasir; Hill, Hannah; Fass, Ronnie; Song, Gengqing","year":2024,"journal":"Gut, 73(2), 246-254","doi":"10.1136/gutjnl-2023-329651","pmid":"37739778","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08734","title":"GLP-1R activation attenuates the progression of pulmonary fibrosis via disrupting NLRP3 inflammasome/PFKFB3-driven glycolysis interaction and histone lactylation.","authors":"Liu, Chenyang; Zhang, Qun; Zhou, Hong; Jin, Linling; Liu, Chang; Yang, Mingxia; Zhao, Xinyun; Ding, Wenqiu; Xie, Weiping; Kong, Hui","year":2024,"journal":"Journal of translational medicine, 22(1), 954","doi":"10.1186/s12967-024-05753-z","pmid":"39434134","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Liraglutide (GLP-1R agonist) attenuated pulmonary inflammation and fibrosis in a silica-induced mouse model. Mechanistically, GLP-1R activation disrupted a newly identified feedback loop between the NLRP3 inflammasome and PFKFB3-driven glycolysis in lung fibroblasts.\n\nInhibiting either the NLRP3 inflammasome or glycolysis suppressed the other, decreasing lactate production. Excess lactate drives histone lactylation — a chemical modification that turns on pro-fibrotic genes. GLP-1R activation blocked this cascade by: (1) disrupting the NLRP3/glycolysis interaction, (2) preventing lactate-mediated histone lactylation, (3) protecting mitochondria from metabolic stress, and (4) suppressing p300-mediated histone lactylation even when lactate was added directly. GLP-1R activation also blocked macrophage-to-fibroblast activation signaling.","whyItMatters":"Pulmonary fibrosis currently has no effective treatment besides lung transplantation. Approved antifibrotic drugs (pirfenidone, nintedanib) only slow progression modestly. Discovering that GLP-1 receptor agonists — drugs already approved and widely used for diabetes — can target fibrosis through a novel metabolic-epigenetic mechanism opens a potentially rapid pathway to clinical testing for this devastating condition.","specificNumbers":"","methodology":"Researchers used a silica-induced pulmonary fibrosis mouse model (C57BL/6 mice) treated with liraglutide in vivo. In vitro experiments used primary lung fibroblasts stimulated with TGF-β1 combined with IL-1β. Cell metabolism assays measured glycolytic rate and mitochondrial respiration. RNA sequencing analyzed molecular mechanisms. ChIP-qPCR evaluated histone lactylation at promoters of pro-fibrotic genes. Additional pharmacological inhibitors (MCC950 for NLRP3, 3PO for PFKFB3) were used to dissect the pathway.","limitations":"The study used a silica-induced fibrosis model in mice, which may not fully replicate human idiopathic pulmonary fibrosis. No human clinical data were presented. The specific liraglutide doses and treatment timing relative to fibrosis onset (prevention vs. treatment) need clarification. Long-term effects and potential for lung-specific delivery were not explored. The complex molecular pathway identified in cell culture may be more nuanced in vivo."},{"rthcId":"RPEP-08735","title":"Administration of Atosiban, an oxytocin receptor antagonist, ameliorates autistic-like behaviors in a female rat model of valproic acid-induced autism.","authors":"Liu, Chunhua; Guo, Zhengyang; Pang, Jiyi; Zhang, Yuying; Yang, Zhuo; Cao, Jianting; Zhang, Tao","year":2024,"journal":"Behavioural brain research, 469, 115052","doi":"10.1016/j.bbr.2024.115052","pmid":"38782096","tags":[],"studyType":"animal","evidenceStrength":"preliminary","keyFinding":"In a valproic acid (VPA)-induced female rat model of autism, researchers found that oxytocin and its receptor were overexpressed in the hippocampus and prefrontal cortex — the opposite of what is typically assumed in autism research, where oxytocin deficiency is the prevailing narrative. Administering exogenous oxytocin to healthy female rats actually triggered autism-like behaviors.\n\nCritically, the oxytocin receptor antagonist Atosiban (a peptide drug) significantly improved multiple autism-like deficits in VPA-exposed female rats, including social interaction impairment, anxiety, and repetitive stereotypical behaviors. Atosiban also improved synaptic plasticity that had been impaired by VPA exposure.","whyItMatters":"Most autism research has focused on males and on the idea that oxytocin supplementation helps social behavior. This study flips that narrative for females, suggesting that in female autism, oxytocin signaling may actually be excessive — and blocking it with a peptide antagonist could be therapeutic. This has significant implications for sex-specific treatment approaches to ASD.","specificNumbers":"","methodology":"Researchers used a VPA-induced autism model in female rats, measuring oxytocin and oxytocin receptor expression in the hippocampus and prefrontal cortex. They tested two interventions: intranasal exogenous oxytocin in wild-type females (to see if excess OXT causes autism-like behavior) and the oxytocin receptor antagonist Atosiban in VPA-exposed females (to see if blocking OXT signaling improves symptoms). Behavioral tests assessed social interaction, anxiety, and stereotypical behaviors, while synaptic plasticity was measured in brain tissue.","limitations":"This is an animal study using a chemically induced autism model in rats, which may not fully recapitulate human ASD. The VPA model represents only one potential pathway to autism. Results in female rats may not directly translate to female humans with ASD. Specific dosing, sample sizes, and effect magnitudes are not detailed in the abstract."},{"rthcId":"RPEP-08736","title":"GLP-1 modulated the firing activity of nigral dopaminergic neurons in both normal and parkinsonian mice.","authors":"Liu, Cui; Liu, Wen-Hong; Yang, Wu; Chen, Lei; Xue, Yan; Chen, Xin-Yi","year":2024,"journal":"Neuropharmacology, 252, 109946","doi":"10.1016/j.neuropharm.2024.109946","pmid":"38599494","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Exendin-4 (GLP-1R agonist) significantly increased the spontaneous firing rate and decreased firing regularity of nigral dopaminergic neurons in normal C57BL/6 mice. Blocking GLP-1 receptors with exendin(9-39) decreased firing rate, confirming that endogenous GLP-1 tonically modulates these neurons.\n\nThe excitatory effect involved PKA signaling and TRPC4/5 (transient receptor potential canonical) ion channels. Critically, both exogenous and endogenous GLP-1 maintained their excitatory effects on surviving dopaminergic neurons in a parkinsonian state. Since mild excitatory stimulation promotes neuroprotection and TH expression in dopamine neurons, the GLP-1-mediated excitation may partially contribute to anti-parkinsonian effects.","whyItMatters":"GLP-1 receptor agonists are already in clinical trials for Parkinson's disease based on epidemiological and early clinical evidence. This study provides a specific neurophysiological mechanism: GLP-1 directly excites the very neurons that are dying in Parkinson's. This is important because understanding why GLP-1 drugs might protect dopamine neurons helps optimize treatment strategies and supports the rationale for larger clinical trials of peptide-based neuroprotection in Parkinson's disease.","specificNumbers":"","methodology":"In vivo extracellular single-unit electrophysiological recordings were performed in the substantia nigra pars compacta of adult male C57BL/6 mice (both normal and parkinsonian models). Exendin-4 was applied as a GLP-1R agonist, and exendin(9-39) as a GLP-1R antagonist. Downstream signaling pathways were investigated using PKA inhibitors and TRPC4/5 channel blockers. Spontaneous firing rate and firing regularity of dopaminergic neurons were the primary outcomes.","limitations":"This is an animal electrophysiology study in mice that may not directly predict effects in the human brain. The parkinsonian model may not fully replicate the complexity of human Parkinson's disease. Only acute GLP-1R activation was studied — chronic effects on neuron survival were not assessed. The neuroprotective conclusion is inferred from the excitatory effect but not directly demonstrated in this study. Specific mouse numbers per experimental condition are not reported in the abstract."},{"rthcId":"RPEP-08737","title":"ST-Segment Alterations in the Electrocardiogram of Acute Pulmonary Thromboembolism: A Rabbit Model.","authors":"Liu, D; Duan, B; Zhao, M; Wu, L; Cao, Y; Liu, N; Xue, Z; He, Z; Mi, J","year":2024,"journal":"Physiological research, 73(4), 543-552","doi":null,"pmid":"39264077","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08738","title":"Collagen study advances for photoaging skin.","authors":"Liu, Helei; Dong, Junjuan; Du, Rina; Gao, Yaoxing; Zhao, Pengwei","year":2024,"journal":"Photodermatology, photoimmunology & photomedicine, 40(1), e12931","doi":"10.1111/phpp.12931","pmid":"38009842","tags":["collagen-peptides","skin-aging","cosmetic-peptides"],"studyType":"Review","evidenceStrength":"Moderate","keyFinding":"UV radiation accelerates skin aging (photoaging) by generating reactive oxygen species that activate matrix metalloproteinases — enzymes that break down collagen. Type I collagen makes up 80–90% of skin collagen, followed by type III (8–12%) and type V (5%). As photoaging progresses, total collagen decreases and the structural matrix of the skin breaks down.\n\nThe review finds that supplementing with collagen and collagen-derived peptides can counteract UV-induced skin damage. Both oral collagen peptide supplements and topical collagen-based products are being used increasingly in biomedical and aesthetic applications to restore collagen levels and improve photoaged skin appearance.","whyItMatters":"Skin photoaging is one of the most visible signs of environmental damage and a major concern driving the cosmetic and dermatological industries. Understanding that collagen loss is central to photoaging — and that collagen peptide supplementation can partially reverse this — supports the growing market for collagen-based skincare products and supplements. This review connects the molecular biology of UV damage with practical supplementation strategies.","specificNumbers":"Type I collagen: 80–90% of skin collagen · Type III: 8–12% · Type V: ~5% · UV increases ROS + MMPs + collagen degradation","methodology":"Narrative review synthesizing research on collagen biology in skin, the mechanisms of UV-induced photoaging, and the effects of collagen and peptide supplementation on photodamaged skin. Also briefly covers other compounds that increase collagen synthesis.","limitations":"As a narrative review, it does not provide a systematic assessment of clinical trial quality or quantitative effect sizes. The abstract does not detail specific clinical studies or their outcomes. Collagen supplementation research varies widely in quality, dose, source (marine, bovine, porcine), and outcome measures. The review may overemphasize positive findings without addressing inconsistencies in the literature. The mechanisms by which oral collagen peptides reach and benefit the skin are still debated."},{"rthcId":"RPEP-08739","title":"Structure of antiviral drug bulevirtide bound to hepatitis B and D virus receptor protein NTCP.","authors":"Liu, Hongtao; Zakrzewicz, Dariusz; Nosol, Kamil; Irobalieva, Rossitza N; Mukherjee, Somnath; Bang-Sørensen, Rose; Goldmann, Nora; Kunz, Sebastian; Rossi, Lorenzo; Kossiakoff, Anthony A; Urban, Stephan; Glebe, Dieter; Geyer, Joachim; Locher, Kaspar P","year":2024,"journal":"Nature communications, 15(1), 2476","doi":"10.1038/s41467-024-46706-w","pmid":"38509088","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08740","title":"Nanopore-based full-length transcriptome sequencing of the skin in Pseudopleuronectes yokohamae identifies novel antimicrobial peptide genes.","authors":"Liu, Hui; Wang, Shuai; Zhang, Zheng; Yan, Huixiang; He, Tingting; Wei, Xiaoyan; Shi, Yanyan; Chen, Yan; Wang, Wei; Li, Xuejie","year":2024,"journal":"Fish & shellfish immunology, 154, 109957","doi":"10.1016/j.fsi.2024.109957","pmid":"39393612","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08741","title":"Histone Deacetylase 7-Derived 7-Amino Acid Peptide Increases Skin Wound Healing via Regulating Epidermal Fibroblast Proliferation and Migration.","authors":"Liu, Huina; Li, Hua; Bai, Xuefeng; Zhao, Yue; Cai, Yannan; Pan, Huiqing; Guo, Linyan; Liu, Kun; Liu, Qian; Huang, Xiaochun; Zampetaki, Anna; Margariti, Andriana; Zeng, Lingfang; Cai, Ting","year":2024,"journal":"Journal of cellular and molecular medicine, 28(22), e70209","doi":"10.1111/jcmm.70209","pmid":"39601342","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08742","title":"A combined in vitro and in silico study of the inhibitory mechanism of angiotensin-converting enzyme with peanut peptides.","authors":"Liu, Jiale; Song, Wentian; Gao, Xue; Sun, Jiaoyan; Liu, Chunlei; Fang, Li; Wang, Ji; Shi, Junhua; Leng, Yue; Liu, Xiaoting; Min, Weihong","year":2024,"journal":"International journal of biological macromolecules, 268(Pt 2), 131901","doi":"10.1016/j.ijbiomac.2024.131901","pmid":"38677685","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08743","title":"Discovery of a new class of cell-penetrating peptides by novel phage display platform.","authors":"Liu, Jinsha; Heddleston, John; Perkins, Douglas Raymond; Chen, Jack Jia Hua; Ghanbarpour, Ahmadreza; Smith, Bill William; Miles, Rebecca; Aihara, Eitaro; Afshar, Sepideh","year":2024,"journal":"Scientific reports, 14(1), 13437","doi":"10.1038/s41598-024-64405-w","pmid":"38862601","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08744","title":"Electrochemical Determination of B-Type Natriuretic Peptide with an Epitope-Imprinted Polymer-Based Sensor.","authors":"Liu, Kai-Hsi; Thomas, James L; Chu, Pei-Chia; Ciou, Jing-Chen; Chen, Chuen-Yau; Lin, Hung-Yin; Lee, Mei-Hwa","year":2024,"journal":"Biosensors, 14(11)","doi":"10.3390/bios14110533","pmid":"39589992","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08745","title":"Thymosin α1 reverses oncolytic adenovirus-induced M2 polarization of macrophages to improve antitumor immunity and therapeutic efficacy.","authors":"Liu, Kua; Kong, Lingkai; Cui, Huawei; Zhang, Louqian; Xin, Qilei; Zhuang, Yan; Guo, Ciliang; Yao, Yongzhong; Tao, Jinqiu; Gu, Xiaosong; Jiang, Chunping; Wu, Junhua","year":2024,"journal":"Cell reports. Medicine, 5(10), 101751","doi":"10.1016/j.xcrm.2024.101751","pmid":"39357524","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Type V adenovirus (ADV) was shown to induce tumor-associated macrophage (TAM) polarization to the immunosuppressive M2 phenotype and increase regulatory T cell (Treg) infiltration in the tumor microenvironment — an immunosuppressive feedback loop that counteracts the virus's anti-cancer effects.\n\nThymosin alpha-1 selectively compensated for these deficiencies by reprogramming M2-like TAMs toward an antitumoral phenotype and reshaping the tumor microenvironment for improved anti-tumor immunity. An engineered adenovirus (ADVTα1) that produces Tα1 directly enhanced anti-tumor efficacy through CD8+ T cell activation, demonstrating that both externally supplied and virus-produced Tα1 effectively orchestrate macrophage reprogramming.","whyItMatters":"Oncolytic virus therapy is one of the most promising frontiers in cancer treatment, but its effectiveness has been limited. This study identifies a specific reason why — the virus inadvertently creates immune suppression — and provides a peptide-based solution. By combining oncolytic viruses with thymosin alpha-1, researchers could potentially overcome a major barrier to effective virus-based cancer immunotherapy.","specificNumbers":"","methodology":"Researchers first characterized the immunosuppressive effects of type V adenovirus on the tumor microenvironment, examining macrophage polarization and Treg infiltration. They then tested thymosin alpha-1 both as an exogenous supplement and as a gene engineered into the adenovirus (ADVTα1). Anti-tumor efficacy was evaluated in mouse cancer models, with immune profiling of the tumor microenvironment including TAM phenotyping and CD8+ T cell analysis.","limitations":"This is a preclinical study in mouse models, and mouse tumor microenvironments differ from human cancers. The specific adenovirus serotype (type V) may have different immunomodulatory effects than other oncolytic viruses. Long-term safety of engineered ADVTα1 was not assessed. Clinical translation would require extensive safety testing given the combination of a replicating virus with an immunomodulatory peptide."},{"rthcId":"RPEP-08746","title":"Comparative Efficacy and Safety of Glucagon-like Peptide-1 Receptor Agonists in Children and Adolescents with Obesity or Overweight: A Systematic Review and Network Meta-Analysis.","authors":"Liu, Ligang; Shi, Hekai; Shi, Yufei; Wang, Anlin; Guo, Nuojin; Tao, Heqing; Nahata, Milap C","year":2024,"journal":"Pharmaceuticals (Basel, Switzerland), 17(7)","doi":"10.3390/ph17070828","pmid":"39065679","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide demonstrated greater efficacy in reducing body weight, BMI, and BMI z-score compared to placebo, exenatide, liraglutide, and dulaglutide in children and adolescents. Semaglutide significantly outperformed exenatide in BMI reduction specifically.\n\nRegarding safety, none of the four GLP-1 RAs were associated with higher risks of diarrhea, headache, or abdominal pain versus placebo. Liraglutide was more likely to cause nausea, vomiting, hypoglycemia, and injection-site reactions compared to both placebo and the other GLP-1 RAs. Semaglutide appeared to be the most effective and safest option overall.","whyItMatters":"Pediatric obesity affects millions of children worldwide and increases lifetime risk of diabetes, heart disease, and other chronic conditions. While multiple GLP-1 peptide drugs are now available, clinicians lacked head-to-head comparison data to guide treatment selection in young patients. This meta-analysis fills that gap by systematically ranking all four available GLP-1 RAs for both efficacy and safety, directly informing clinical decision-making for a vulnerable population.","specificNumbers":"","methodology":"Systematic review and network meta-analysis of randomized controlled trials (RCTs). Embase, PubMed, and Scopus were searched through June 2024. Eleven RCTs with 953 participants comparing semaglutide, exenatide, liraglutide, and dulaglutide were included. Primary efficacy outcomes were changes in body weight, BMI, BMI z-score, and waist circumference. Safety outcomes included nausea, vomiting, diarrhea, abdominal pain, injection-site reactions, and hypoglycemia.","limitations":"The analysis included 953 participants across 11 trials, which is moderate but still limited for network meta-analysis. Individual trial designs, durations, dosing protocols, and patient characteristics varied. The search was last updated in June 2024, so newer trials may not be included. Long-term safety data (beyond trial durations) in growing children are still limited. Tirzepatide (dual GIP/GLP-1 agonist) was not included, as pediatric data may not have been available at the time of analysis."},{"rthcId":"RPEP-08747","title":"Efficacy and safety of tirzepatide versus placebo in overweight or obese adults without diabetes: a systematic review and meta-analysis of randomized controlled trials.","authors":"Liu, Ligang; Shi, Hekai; Xie, Merilyn; Sun, Yuxiao; Nahata, Milap C","year":2024,"journal":"International journal of clinical pharmacy, 46(6), 1268-1280","doi":"10.1007/s11096-024-01779-x","pmid":"39037553","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08748","title":"A real-world data analysis of tirzepatide in the FDA adverse event reporting system (FAERS) database.","authors":"Liu, Liyuan","year":2024,"journal":"Frontiers in pharmacology, 15, 1397029","doi":"10.3389/fphar.2024.1397029","pmid":"38910884","tags":["glp-1-peptides","gip-peptides","drug-safety"],"studyType":"Pharmacovigilance / Database Analysis","evidenceStrength":"Moderate","keyFinding":"Analysis of the FDA's adverse event database (FAERS) identified 46 tirzepatide-associated adverse drug reactions across 8 organ system classes from over 1.9 million reports between Q2 2022 and Q3 2023.\n\nMany identified adverse events were expected and consistent with drug labeling, including gastroesophageal reflux disease, dyspepsia, and vomiting. However, the analysis also uncovered unexpected signals including incorrect dose administered, injection site hemorrhage, and paradoxically increased appetite. These unexpected signals were associated with injury/procedural complications, general disorders, and metabolic/nutritional disturbances.","whyItMatters":"Tirzepatide (Mounjaro/Zepbound) has rapidly become one of the most prescribed medications in the world, but clinical trials only capture a limited picture of safety. Real-world adverse event data from millions of reports provides a broader view of what actually happens when diverse patient populations use the drug outside of controlled trial settings. Identifying unexpected signals like dosing errors and injection site hemorrhage helps guide prescriber education and patient monitoring, while the paradoxical finding of increased appetite in some patients challenges assumptions about the drug's mechanism.","specificNumbers":"1,904,481 case reports · Q2 2022 to Q3 2023 · 46 adverse drug reactions identified · 8 system organ classes · 4 statistical methods used (ROR, PRR, BCPNN, EBGM)","methodology":"The researchers extracted tirzepatide-associated adverse event reports from the FDA Adverse Event Reporting System (FAERS) database covering Q2 2022 through Q3 2023. They used four established disproportionality analysis methods — reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayes geometric mean (EBGM) — to detect statistically significant safety signals. Results were classified using the MedDRA (Medical Dictionary for Regulatory Activities) coding system.","limitations":"FAERS is a voluntary reporting system subject to reporting bias — adverse events may be over- or under-reported, and reports do not prove causation. The database cannot establish incidence rates since the total number of patients using the drug is unknown. Reports may contain duplicates, incomplete information, or confounding factors from co-medications. The analysis period covers only the first ~18 months after approval when reporting rates tend to be higher."},{"rthcId":"RPEP-08749","title":"Semaglutide Alleviates Ovary Inflammation via the AMPK/SIRT1/NF‑κB Signaling Pathway in Polycystic Ovary Syndrome Mice.","authors":"Liu, Mei; Guo, Sili; Li, Xiaohan; Tian, Yang; Yu, Yanjie; Tang, Lili; Sun, Qimei; Zhang, Ting; Fan, Mingwei; Zhang, Lili; Xu, Yingjiang; An, Jiajia; Gao, Xiangqian; Han, Lei; Zhang, Lei","year":2024,"journal":"Drug design, development and therapy, 18, 3925-3938","doi":"10.2147/DDDT.S484531","pmid":"39247793","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08750","title":"Old concepts, new tricks: How peptide vaccines are reshaping cancer immunotherapy?","authors":"Liu, Qingyang; Wu, Peihua; Lei, Jun; Bai, Peng; Zhong, Peiluan; Yang, Min; Wei, Pengcheng","year":2024,"journal":"International journal of biological macromolecules, 279(Pt 4), 135541","doi":"10.1016/j.ijbiomac.2024.135541","pmid":"39270889","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08751","title":"Chemical composition, health benefits, food processing effects and applications of Boletus: a review.","authors":"Liu, Qiuming; Sun, Liping; Ding, Yangyue; Zhuang, Yongliang","year":2024,"journal":"Critical reviews in food science and nutrition, 64(29), 10812-10834","doi":"10.1080/10408398.2023.2229426","pmid":"37395409","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08752","title":"Mechanisms of action and therapeutic applications of GLP-1 and dual GIP/GLP-1 receptor agonists.","authors":"Liu, Qiyuan Keith","year":2024,"journal":"Frontiers in endocrinology, 15, 1431292","doi":"10.3389/fendo.2024.1431292","pmid":"39114288","tags":["glp-1","mechanism-of-action"],"studyType":"review","evidenceStrength":"strong","keyFinding":"This review maps out how the two incretin hormones — GIP and GLP-1 — work across multiple organ systems and why combining their actions in dual agonist drugs produces superior metabolic effects. Key mechanistic differences include: both suppress appetite through brain satiety centers, both stimulate insulin from beta cells, but they diverge on glucagon — GIP promotes glucagon release during low blood sugar (protective against hypoglycemia) while GLP-1 suppresses glucagon during high blood sugar. On fat metabolism, GIP directly promotes fat storage in appropriate tissue while GLP-1 indirectly promotes fat breakdown, and together they maintain healthy fat distribution, reduce ectopic fat, and boost adiponectin secretion.\n\nThis complementary biology explains why dual GIP/GLP-1 agonists like tirzepatide can achieve greater weight loss and metabolic improvement than GLP-1-only drugs, while the GIP component provides a safety buffer against hypoglycemia.","whyItMatters":"Understanding why dual agonists outperform single GLP-1 agonists is crucial as the field moves toward triple agonists and next-generation metabolic drugs. This review provides the mechanistic roadmap: GIP and GLP-1 are not redundant — they have complementary and sometimes opposing effects that together create a more balanced metabolic intervention. This knowledge guides the development of future drugs with better efficacy and fewer side effects.","specificNumbers":"2 incretin hormones (GIP and GLP-1) · Multiple tissue targets: brain, pancreatic β-cells, α-cells, adipocytes · Complementary effects on glucagon: glucagonotropic (GIP) vs glucagonostatic (GLP-1)","methodology":"This is a narrative review published in Frontiers in Endocrinology that synthesizes published research on the cellular and molecular mechanisms of GIP and GLP-1 signaling across multiple tissues. The author reviews the pharmacology of approved GLP-1 and dual GIP/GLP-1 receptor agonists and their clinical trial outcomes in type 2 diabetes, obesity, and cardiovascular disease.","limitations":"As a narrative review by a single author, it reflects one perspective on the literature rather than a systematic synthesis. Some mechanistic details are derived from preclinical studies that may not fully translate to humans. The review does not provide quantitative comparisons between specific drugs or detail their side effect profiles. Rapidly evolving clinical trial data means some conclusions may already be outdated."},{"rthcId":"RPEP-08753","title":"Thermodynamically stable ionic liquid microemulsions pioneer pathways for topical delivery and peptide application.","authors":"Liu, Tianqi; Liu, Ying; Zhao, Xiaoyu; Zhang, Liguo; Wang, Wei; Bai, De; Liao, Ya; Wang, Zhenyuan; Wang, Mi; Zhang, Jiaheng","year":2024,"journal":"Bioactive materials, 32, 502-513","doi":"10.1016/j.bioactmat.2023.10.002","pmid":"38026438","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The ionic liquid-based microemulsion (IL-M) system improved local delivery of GHK-Cu copper peptide through the skin by approximately three-fold compared to conventional delivery while retaining biological function. Mouse experiments confirmed the system's effectiveness for hair growth.\n\nMechanistically, the IL-M system increased activation of the Wnt/β-catenin signaling pathway — a critical regulator of hair follicle cycling and growth — and upregulated vascular endothelial growth factor (VEGF) expression, which promotes the blood supply to hair follicles. The microemulsion itself was thermodynamically stable, meaning it doesn't separate or degrade over time, which is important for product shelf life.","whyItMatters":"Hair loss (alopecia) affects approximately 50% of men and 25% of women, with limited effective treatments. Minoxidil and finasteride, the current standard treatments, have significant side effects (finasteride can cause sexual dysfunction; minoxidil can cause skin irritation and unwanted facial hair growth). GHK-Cu is a naturally occurring peptide with established hair-growth-promoting properties and minimal side effects, but its large molecular size prevents effective skin penetration. Solving this delivery challenge could make copper peptide a practical, safer alternative to current hair loss treatments.","specificNumbers":"","methodology":"The IL-M system was designed using theoretical calculations and pseudo-ternary phase diagrams to identify optimal formulation compositions. Skin permeation was measured in vitro. In vivo efficacy was tested in a mouse hair growth model. Molecular analysis assessed expression of VEGF and Wnt/β-catenin pathway components. Safety and stability were evaluated through standard assays.","limitations":"The study was conducted in mice, whose skin barrier differs from human skin in thickness and composition. The approximately three-fold improvement in delivery, while significant, may or may not be sufficient for clinical efficacy in humans. Long-term safety data for ionic liquid formulations on human skin is limited. The specific composition of the ionic liquid and its potential for skin sensitization or irritation with prolonged use need further evaluation. No human clinical trial data was presented."},{"rthcId":"RPEP-08754","title":"Transcriptomic analysis of skin immunity genes in the Chinese spiny frog (Quasipaa spinosa) after Proteus mirabilis infection.","authors":"Liu, Wei; Tao, Yu-Hui; Lu, Cheng-Pu; Zhang, Le; Chen, Jie; Lin, Zhi-Hua","year":2024,"journal":"Comparative biochemistry and physiology. Part D, Genomics & proteomics, 49, 101172","doi":"10.1016/j.cbd.2023.101172","pmid":"38056223","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08755","title":"Application of the integrated data platform combined with dietary management for adults with diabetes: A prospective randomized controlled trial.","authors":"Liu, Xiyu; Wang, Xiaohong; Xie, Mengxun; Cao, Lulu","year":2024,"journal":"Journal of diabetes investigation, 15(11), 1548-1555","doi":"10.1111/jdi.14296","pmid":"39171608","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08756","title":"Mitochondria-targeting peptide SS-31 attenuates ferroptosis via inhibition of the p38 MAPK signaling pathway in the hippocampus of epileptic rats.","authors":"Liu, Xue; Wang, Fei-Yu; Chi, Song; Liu, Tao; Yang, Hai-Lin; Zhong, Ru-Jie; Li, Xiao-Yu; Gao, Jing","year":2024,"journal":"Brain research, 1836, 148882","doi":"10.1016/j.brainres.2024.148882","pmid":"38521160","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08757","title":"Exendin-4, a glucagon-like peptide-1 receptor agonist, regulates ductus arteriosus by vasodilation and anti-remodeling through the PKA pathway.","authors":"Liu, Yi-Ching; Tseng, Yu-Hsin; Wu, Yen-Hsien; Tong, Lorraine; Tsai, Siao-Ping; Huang, Shang-En; Wu, Bin-Nan; Lo, Shih-Hsing; Chen, I-Chen; Dai, Zen-Kong; Yeh, Jwu-Lai; Hsu, Jong-Hau","year":2024,"journal":"European journal of pharmacology, 985, 177106","doi":"10.1016/j.ejphar.2024.177106","pmid":"39515563","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Exendin-4 (Ex-4), a GLP-1 receptor agonist, maintained ductus arteriosus (DA) patency in neonatal rats by preventing spontaneous closure that normally occurs within two hours after birth. Ex-4 reduced intimal thickening, attenuated oxygen-induced vasoconstriction in isolated DA rings, and inhibited PDGF-BB-induced proliferation, migration, ROS production, and calcium mobilization in DA smooth muscle cells. All of these effects were blocked by H89, a PKA inhibitor, establishing the GLP-1R/PKA pathway as the mechanism of action.","whyItMatters":"Patent ductus arteriosus (PDA) is a common condition in premature infants where the blood vessel connecting the aorta to the pulmonary artery fails to close after birth — or in some cases, needs to be kept open therapeutically. This study reveals a new mechanism through which GLP-1 receptor agonists could be used to manage DA patency, potentially offering a novel pharmacological approach for neonates with congenital heart conditions.","specificNumbers":"","methodology":"The researchers first confirmed GLP-1 receptor expression in neonatal rat DA tissue. They then tested exendin-4 in vivo by observing DA closure in neonatal rats at two hours after birth, comparing treated animals to controls. Ex vivo experiments measured oxygen-induced vasoconstriction in isolated DA rings. In vitro experiments on DA smooth muscle cells assessed proliferation, migration, ROS production, calcium mobilization, and signaling pathways (MAPK, Akt, Nrf2), with and without the PKA inhibitor H89.","limitations":"This study was conducted entirely in neonatal rats, so the findings may not directly translate to human neonates. The abstract does not report specific quantitative results (effect sizes, p-values) for any of the experiments. The PKA pathway was identified using a single pharmacological inhibitor (H89) rather than genetic approaches, which could be less specific."},{"rthcId":"RPEP-08758","title":"Self-assembled peptide hydrogel loaded with functional peptide Dentonin accelerates vascularized bone tissue regeneration in critical-size bone defects.","authors":"Liu, Yijuan; Li, Li; He, Mengjiao; Xu, Yanmei; Wu, Zekai; Xu, Xiongcheng; Luo, Kai; Lv, Hongbing","year":2024,"journal":"Regenerative biomaterials, 11, rbae106","doi":"10.1093/rb/rbae106","pmid":"39263324","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08759","title":"Unveiling the therapeutic potential of Dl-3-n-butylphthalide in NTG-induced migraine mouse: activating the Nrf2 pathway to alleviate oxidative stress and neuroinflammation.","authors":"Liu, Yingyuan; Gong, Zihua; Zhai, Deqi; Yang, Chunxiao; Lu, Guangshuang; Wang, Shuqing; Xiao, Shaobo; Li, Chenhao; Chen, Ludan; Lin, Xiaoxue; Zhang, Shuhua; Yu, Shengyuan; Dong, Zhao","year":2024,"journal":"The journal of headache and pain, 25(1), 50","doi":"10.1186/s10194-024-01750-1","pmid":"38565987","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08760","title":"Dietary collagen peptide-chelated trace elements supplementation for breeder hens improves the intestinal health of chick offspring.","authors":"Liu, Yongfa; Li, Simeng; Huang, Zhenwu; Dai, Hongjian; Shi, Fangxiong; Lv, Zengpeng","year":2024,"journal":"Journal of the science of food and agriculture, 104(1), 174-183","doi":"10.1002/jsfa.12938","pmid":"37612258","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08761","title":"A comparative study of acupuncture combined with rehabilitation gymnastics on postoperative anal function of lower rectal cancer.","authors":"Liu, Zhan-Lun; He, Yi-Wei; Liu, Yan-Feng; Wang, Ni; Li, Wei; Shen, Li-Zhong","year":2024,"journal":"World journal of clinical cases, 12(18), 3491-3496","doi":"10.12998/wjcc.v12.i18.3491","pmid":"38983403","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08762","title":"Incretin Analogs for Weight Management in Adults Without Diabetes.","authors":"Lobkovich, Alison; Kale-Pradhan, Pramodini; Lipari, Melissa","year":2024,"journal":"The Annals of pharmacotherapy, 58(4), 398-406","doi":"10.1177/10600280231190089","pmid":"37522468","tags":[],"studyType":"Narrative Review","evidenceStrength":"strong","keyFinding":"Across 15 randomized controlled trials in adults without diabetes, all three incretin analogs produced significant weight loss compared to placebo. Tirzepatide delivered the most weight loss at 15-20.9%, followed by semaglutide at 14.9-17.4%, and liraglutide at 5.7-11.8%. All agents were superior to placebo, with gastrointestinal side effects (nausea, vomiting, diarrhea) being the most common adverse events across all three drugs.\n\nThe review establishes a clear hierarchy: tirzepatide (the dual GLP-1/GIP agonist) outperforms semaglutide (a GLP-1 agonist), which in turn substantially outperforms liraglutide (the older GLP-1 agonist). The American Gastroenterological Association already recommends GLP-1 agonists as preferred pharmacotherapy for overweight or obese patients.","whyItMatters":"This review provides a concise head-to-head comparison of the three approved incretin analogs for weight management in non-diabetic adults. With the weight loss drug market exploding, patients and clinicians need clear comparisons. The data shows a meaningful progression in efficacy from first-generation (liraglutide) to current-generation (tirzepatide) peptide drugs, with tirzepatide nearly quadrupling liraglutide's minimum weight loss.","specificNumbers":"15 RCTs reviewed · Liraglutide: 5.7-11.8% weight loss · Semaglutide: 14.9-17.4% weight loss · Tirzepatide: 15-20.9% weight loss · GI adverse effects most common · All superior to placebo","methodology":"Narrative review of randomized controlled trials identified through PubMed/MEDLINE, Scopus, and Embase from inception through June 2023. Included studies of adults without diabetes treated with liraglutide, semaglutide, or tirzepatide for weight management with weight loss as a primary outcome. Fifteen studies met inclusion criteria.","limitations":"Narrative review rather than a systematic review or meta-analysis, so study selection may not be fully reproducible. Direct head-to-head trials between the three drugs are limited — weight loss ranges come from different trial populations and protocols. Literature search ends June 2023, so more recent data (including newer dose formulations) is not captured. Does not address long-term weight maintenance after stopping treatment."},{"rthcId":"RPEP-08763","title":"Incretin-Based Weight Loss Pharmacotherapy: Can Resistance Exercise Optimize Changes in Body Composition?","authors":"Locatelli, João Carlos; Costa, Juliene Gonçalves; Haynes, Andrew; Naylor, Louise H; Fegan, P Gerry; Yeap, Bu B; Green, Daniel J","year":2024,"journal":"Diabetes care, 47(10), 1718-1730","doi":"10.2337/dci23-0100","pmid":"38687506","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08764","title":"GLP-1 agonists: A review for emergency clinicians.","authors":"Long, Brit; Pelletier, Jessica; Koyfman, Alex; Bridwell, Rachel E","year":2024,"journal":"The American journal of emergency medicine, 78, 89-94","doi":"10.1016/j.ajem.2024.01.010","pmid":"38241775","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08765","title":"The Use of Semaglutide in Patients With Renal Failure-A Retrospective Cohort Study.","authors":"Long, Jane J; Sahi, Sukhdeep S; Lemke, Adley I; Na, Jie; Garcia Valencia, Oscar A; Budhiraja, Pooja; Wadei, Hani M; Sudhindran, Vineeth; Benzo, Roberto; Clark, Matthew M; Shah, Meera; Fipps, David; Navratil, Pavel; Abdelrheem, Ahmed A; Shaik, Afsana A; Duffy, Dustin J; Pencovich, Niv; Shah, Pankaj; Kudva, Yogish C; Kukla, Aleksandra; Diwan, Tayyab S","year":2024,"journal":"Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists, 30(10), 963-969","doi":"10.1016/j.eprac.2024.07.008","pmid":"39025300","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08766","title":"Tirzepatide for Metabolic Dysfunction-Associated Steatohepatitis with Liver Fibrosis.","authors":"Loomba, Rohit; Hartman, Mark L; Lawitz, Eric J; Vuppalanchi, Raj; Boursier, Jérôme; Bugianesi, Elisabetta; Yoneda, Masato; Behling, Cynthia; Cummings, Oscar W; Tang, Yuanyuan; Brouwers, Bram; Robins, Deborah A; Nikooie, Amir; Bunck, Mathijs C; Haupt, Axel; Sanyal, Arun J","year":2024,"journal":"The New England journal of medicine, 391(4), 299-310","doi":"10.1056/NEJMoa2401943","pmid":"38856224","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08767","title":"Beyond Transduction: Anti-Inflammatory Effects of Cell Penetrating Peptides.","authors":"Lopuszynski, Jack; Wang, Jingyu; Zahid, Maliha","year":2024,"journal":"Molecules (Basel, Switzerland), 29(17)","doi":"10.3390/molecules29174088","pmid":"39274936","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08768","title":"The Beneficial Effects of GLP-1 Receptor Agonists Other than Their Anti-Diabetic and Anti-Obesity Properties.","authors":"Lu, Chenqi; Xu, Cong; Yang, Jun","year":2024,"journal":"Medicina (Kaunas, Lithuania), 61(1)","doi":"10.3390/medicina61010017","pmid":"39858999","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identified multiple beneficial effects of GLP-1 receptor agonists beyond their established roles in diabetes and obesity management. These include reducing ischemia-reperfusion injury (damage caused when blood flow returns after being cut off), improving function across various organs, alleviating substance use disorders, influencing tumor development, regulating bone metabolism, modifying gut microbiota composition, and prolonging the survival of transplanted organs.\n\nThese diverse effects point to GLP-1 receptors being present and functionally important in many tissues throughout the body, not just the pancreas and brain regions controlling appetite.","whyItMatters":"GLP-1 receptor agonists like semaglutide and liraglutide are among the most widely prescribed drugs in the world. Understanding their effects beyond blood sugar and weight could reshape how they are used clinically — potentially benefiting patients with heart disease, addiction, organ transplants, and other conditions. This broadening scope may also reveal new insights about how GLP-1 signaling works throughout the body.","specificNumbers":"","methodology":"This is a narrative review article that summarized published research on the non-diabetic and non-obesity-related effects of GLP-1 receptor agonists. The authors compiled findings from existing studies across multiple therapeutic areas.","limitations":"As a narrative review, this paper summarizes existing research but does not conduct new experiments or perform a systematic meta-analysis. The strength of evidence varies widely across the different benefit categories discussed — some are supported by large clinical trials while others rely on preclinical animal data. The review does not assess the quality or risk of bias across the cited studies."},{"rthcId":"RPEP-08769","title":"Antimicrobial Peptides From the Gut Microbiome of the Centenarians: Diversification of Biosynthesis and Youthful Development of Resistance Genes.","authors":"Lu, Chunrong; Wang, Xiaojun; Ye, Pengpeng; Lu, Zhilong; Ma, Jie; Luo, Weifei; Wang, Shuai; Chen, Xiaochun","year":2024,"journal":"The journals of gerontology. Series A, Biological sciences and medical sciences, 79(11)","doi":"10.1093/gerona/glae218","pmid":"39207726","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08770","title":"AMPK activation attenuates central sensitization in a recurrent nitroglycerin-induced chronic migraine mouse model by promoting microglial M2-type polarization.","authors":"Lu, Guangshuang; Xiao, Shaobo; Meng, Fanchao; Zhang, Leyi; Chang, Yan; Zhao, Jinjing; Gao, Nan; Su, Wenjie; Guo, Xinghao; Liu, Yingyuan; Li, Chenhao; Tang, Wenjing; Zou, Liping; Yu, Shengyuan; Liu, Ruozhuo","year":2024,"journal":"The journal of headache and pain, 25(1), 29","doi":"10.1186/s10194-024-01739-w","pmid":"38454376","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In a chronic migraine mouse model, repeated nitroglycerin injections progressively decreased AMPK protein expression in the trigeminal nucleus caudalis (TNC), mediated by increased UHRF1 expression. Activating AMPK with AICAR reduced pain hypersensitivity, improved activity, and decreased CGRP and pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) while increasing anti-inflammatory cytokines (IL-4, IL-10). AMPK was located primarily in microglia, and AICAR shifted microglia from the inflammatory M1 phenotype (reduced iNOS) to the anti-inflammatory M2 phenotype (increased Arg1) by inhibiting the NF-κB pathway.","whyItMatters":"Chronic migraine involves central sensitization — where the brain's pain processing becomes amplified — but the underlying mechanisms are poorly understood. This study reveals that AMPK, a cellular energy sensor, plays a key role by controlling whether brain immune cells (microglia) promote or suppress inflammation. The involvement of CGRP, the peptide targeted by the newest migraine drugs, connects this metabolic pathway directly to the established biology of migraine treatment.","specificNumbers":"","methodology":"Chronic migraine was modeled in mice using recurrent nitroglycerin (NTG) injections. AMPK protein expression was measured in the TNC. Mice received either the AMPK activator AICAR or the inhibitor compound C via intraperitoneal injection. Researchers measured mechanical pain thresholds, activity levels, pain-like behaviors, CGRP expression, cytokine levels (IL-1β, IL-6, TNF-α, IL-4, IL-10), microglial M1/M2 polarization markers (iNOS, Arg1), and NF-κB pathway activation.","limitations":"This is a preclinical mouse study using a chemical (nitroglycerin) model of chronic migraine, which may not fully recapitulate human migraine pathophysiology. AICAR was delivered by intraperitoneal injection, and its brain penetrance and specificity for AMPK may limit translational relevance. Specific quantitative results (fold changes, p-values for behavioral measures) are not reported in the abstract. The connection to human CGRP-targeted therapies is mechanistic inference, not direct clinical evidence."},{"rthcId":"RPEP-08771","title":"Reconsidering Semaglutide Use for Chronic Obesity in Patients of Asian Descent: A Critical Review.","authors":"Lu, Jenny; Williams, Grace; Fanning, Stacey","year":2024,"journal":"Cureus, 16(11), e73111","doi":"10.7759/cureus.73111","pmid":"39650923","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"This review argues that Asian Americans may be unfairly excluded from semaglutide prescriptions for chronic weight management because current eligibility criteria rely on BMI thresholds that don't account for ethnicity-specific differences in body composition. Asians develop metabolic syndrome — including visceral fat accumulation, insulin resistance, and cardiovascular risk — at lower BMI levels than other populations. The review calls for integrating visceral fat measurements and other ethnicity-specific risk predictors into the diagnostic and prescribing framework for metabolic syndrome and semaglutide access.","whyItMatters":"Semaglutide prescribing guidelines use BMI cutoffs (typically ≥30 or ≥27 with comorbidities) that were developed primarily in Western populations. Asian populations develop metabolic complications at lower BMIs, meaning many Asian Americans with genuine metabolic syndrome may not qualify for semaglutide. This review highlights a significant health equity issue: standard prescription criteria may systematically deny effective treatment to an entire population group.","specificNumbers":"","methodology":"Critical narrative review of existing literature on semaglutide's use for chronic weight management, metabolic syndrome diagnosis, and ethnicity-specific body composition differences in Asian populations. No new data were collected.","limitations":"This is a narrative review published in Cureus (an open-access journal with less rigorous peer review than top-tier journals). It does not provide new data or systematic analysis. The arguments, while clinically important, are based on synthesized existing evidence rather than original research specifically testing different BMI thresholds for semaglutide in Asian populations."},{"rthcId":"RPEP-08772","title":"Mitochondrial-derived peptides, HNG and SHLP3, protect cochlear hair cells against gentamicin.","authors":"Lu, Yu; Bartoszek, Ewelina M; Cortada, Maurizio; Bodmer, Daniel; Levano Huaman, Soledad","year":2024,"journal":"Cell death discovery, 10(1), 445","doi":"10.1038/s41420-024-02215-9","pmid":"39433756","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08773","title":"The growth hormone secretagogue receptor 1a agonists, anamorelin and ipamorelin, inhibit cisplatin-induced weight loss in ferrets: Anamorelin also exhibits anti-emetic effects via a central mechanism.","authors":"Lu, Zengbing; Ngan, Man P; Liu, Julia Y H; Yang, Lingqing; Tu, Longlong; Chan, Sze Wa; Giuliano, Claudio; Lovati, Emanuela; Pietra, Claudio; Rudd, John A","year":2024,"journal":"Physiology & behavior, 284, 114644","doi":"10.1016/j.physbeh.2024.114644","pmid":"39043357","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Both ghrelin mimetics — anamorelin and ipamorelin — inhibited cisplatin-induced weight loss by approximately 24% during the delayed phase (48-72 hours) when administered intraperitoneally. Neither reduced emesis via this route. However, anamorelin administered directly into the brain (intracerebroventricularly) reduced acute emesis by 60%, improved food and water consumption by 20-40% during the acute phase, and reduced weight loss by ~23% during the delayed phase. In isolated ileum, anamorelin inhibited contractions by 94.4% (IC50 = 14.0 µM) while ipamorelin achieved 54.4% (IC50 = 11.7 µM). The findings suggest brain penetration is critical for anamorelin's anti-emetic effect.","whyItMatters":"Chemotherapy-induced nausea, vomiting, and weight loss (cachexia) are among the most distressing side effects of cancer treatment and major reasons patients discontinue therapy. Anamorelin, a ghrelin receptor agonist already approved in some countries for cancer cachexia, may have broader utility as an anti-emetic if formulated to cross the blood-brain barrier. This study provides mechanistic evidence for a dual role — appetite stimulation plus nausea reduction — through a central nervous system mechanism.","specificNumbers":"","methodology":"Ferrets were used as the animal model (standard for emesis research, as rodents cannot vomit). Anamorelin (1-3 mg/kg) or ipamorelin (1-3 mg/kg) were administered intraperitoneally 30 seconds before cisplatin (5 mg/kg) and then every 24 hours, with behavior recorded for 72 hours. Food and water consumption was measured every 24 hours. Separate experiments tested intracerebroventricular anamorelin (10 µg). Ex vivo experiments measured electrical field stimulation-induced contractions of isolated ferret ileum to assess peripheral gut effects.","limitations":"Ferret studies, while the gold standard for emesis research, may not directly predict human responses. The intracerebroventricular route used to demonstrate anti-emetic effects is not clinically practical — whether a brain-penetrant formulation of anamorelin could achieve the same effect is unknown. Sample sizes per group are not reported in the abstract. Ipamorelin was not tested intracerebroventricularly, so it's unclear whether it would show similar central anti-emetic effects."},{"rthcId":"RPEP-08774","title":"Clinical Significance of B-Type Natriuretic Peptide and N-Terminal Pro-B-Type Natriuretic Peptide in Pediatric Patients: Insights into Their Utility in the Presence or Absence of Pre-Existing Heart Conditions.","authors":"Ludwikowska, Kamila Maria; Tokarczyk, Monika; Paleczny, Bartłomiej; Tracewski, Paweł; Szenborn, Leszek; Kusa, Jacek","year":2024,"journal":"International journal of molecular sciences, 25(16)","doi":"10.3390/ijms25168781","pmid":"39201467","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08775","title":"A comprehensive review of advanced nasal delivery: Specially insulin and calcitonin.","authors":"Luo, Dan; Ni, Xiaoqing; Yang, Hao; Feng, Lu; Chen, Zhaoqun; Bai, Lan","year":2024,"journal":"European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 192, 106630","doi":"10.1016/j.ejps.2023.106630","pmid":"37949195","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08776","title":"Restoring brain health: Electroacupuncture at GB20 and LR3 for migraine mitigation through mitochondrial restoration.","authors":"Luo, Jianchang; Feng, Liyao; Wang, Luodan; Fang, Zhenyu; Lang, Jiawang; Lang, Boxu","year":2024,"journal":"Brain circulation, 10(2), 154-161","doi":"10.4103/bc.bc_95_23","pmid":"39036293","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08777","title":"Novel Tree Shrew-Derived Antimicrobial Peptide with Broad-Spectrum Antibacterial Activity.","authors":"Luo, Lin; Cai, Ying; Su, Yunhan; Li, Chenxi; Tian, Gengzhou; Wang, Xingyu; Wu, Zhongxiang; Chen, Wenlin; Zhang, Tianyu; Zhang, Zhiye","year":2024,"journal":"ACS omega, 9(45), 45279-45288","doi":"10.1021/acsomega.4c06857","pmid":"39554445","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Researchers engineered a novel antimicrobial peptide called TC-LAR-18 from a tree shrew cathelicidin by increasing its net positive charge from +4 to +8. The modified peptide showed 4- to 128-fold stronger antibacterial activity than the original TC-33, effectively killed both free-floating and biofilm-associated bacteria, and caused no hemolysis or cytotoxicity at concentrations up to 100 μg/mL.\n\nCritically, TC-LAR-18 demonstrated rapid membrane-disrupting action with a low tendency to induce bacterial resistance, and provided significant protection against skin bacterial infections in a mouse model.","whyItMatters":"Antibiotic resistance is one of the most urgent global health threats. Antimicrobial peptides represent an alternative approach because bacteria have difficulty developing resistance to them. This study shows that rational design — specifically increasing positive charge — can dramatically improve a natural peptide's killing power while maintaining safety, potentially yielding new weapons against multidrug-resistant infections.","specificNumbers":"","methodology":"The researchers took a natural cathelicidin antimicrobial peptide (TC-33) from the Chinese tree shrew and redesigned it through peptide truncation and glutamic acid substitutions to increase its net positive charge. They then tested TC-LAR-18's antibacterial activity against multiple bacterial species (planktonic and biofilm), assessed safety via hemolysis and cytotoxicity assays, evaluated resistance induction potential, and tested therapeutic efficacy in a mouse skin infection model.","limitations":"The study only tested TC-LAR-18 in a skin infection mouse model; efficacy against systemic infections is unknown. Long-term safety and pharmacokinetic profiles were not assessed. The peptide's stability in biological fluids and potential for large-scale production were not addressed in this study."},{"rthcId":"RPEP-08778","title":"Optimizing Nav1.7-Targeted Analgesics: Revealing Off-Target Effects of Spider Venom-Derived Peptide Toxins and Engineering Strategies for Improvement.","authors":"Luo, Sen; Zhou, Xi; Wu, Meijing; Wang, Gongxin; Wang, Li; Feng, Xujun; Wu, Hang; Luo, Ren; Lu, Minjuan; Ju, Junxian; Wang, Wenxing; Yuan, Lei; Luo, Xiaoqing; Peng, Dezheng; Yang, Li; Zhang, Qingfeng; Chen, Minzhi; Liang, Songping; Dong, Xiuming; Hao, Guoliang; Zhang, Yunxiao; Liu, Zhonghua","year":2024,"journal":"Advanced science (Weinheim, Baden-Wurttemberg, Germany), 11(42), e2406656","doi":"10.1002/advs.202406656","pmid":"39248322","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08779","title":"Cationicity Enhancement on the Hydrophilic Face of Ctriporin Significantly Reduces Its Hemolytic Activity and Improves the Antimicrobial Activity against Antibiotic-Resistant ESKAPE Pathogens.","authors":"Luo, Xudong; Deng, Huan; Ding, Li; Ye, Xiangdong; Sun, Fang; Qin, Chenhu; Chen, Zongyun","year":2024,"journal":"Toxins, 16(3)","doi":"10.3390/toxins16030156","pmid":"38535822","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08780","title":"Review article: Pharmacologic management of obesity - updates on approved medications, indications and risks.","authors":"Lupianez-Merly, Camille; Dilmaghani, Saam; Vosoughi, Kia; Camilleri, Michael","year":2024,"journal":"Alimentary pharmacology & therapeutics, 59(4), 475-491","doi":"10.1111/apt.17856","pmid":"38169126","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08781","title":"INDIVIDUAL ARTICLE: Real-World Clinical Experience With a Neuro-Peptide Serum in Combination With Botulinum Toxin Type-A Injections.","authors":"Lupin, Mark; Bjerring, Peter; Andriessen, Anneke; Chantrey, Jonquille; Fabi, Sabrina Guillen; Liew, Steven; McDonald, Cara; Xiaolei, Qin; White, Stacy","year":2024,"journal":"Journal of drugs in dermatology : JDD, 23(11), 43661s3-43661s14","doi":null,"pmid":"39496132","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A topical neuropeptide serum containing 2% acetyl hexapeptide-8, 2% dipeptide diaminobutyroyl, 5% polyhydroxy acids, 5% niacinamide, and 1% laminaria extract appeared to complement botulinum toxin type-A (BTX-A) injections in real-world clinical use. Seven clinicians (5 dermatologists and 2 surgeons) reported that the combination improved skin radiance, reduced fine lines, and reduced wrinkles in diverse patients when the serum was applied twice daily alongside BTX-A injections. The serum reportedly works by stimulating 9 key skin biomarkers.","whyItMatters":"Botulinum toxin injections are widely used for wrinkle reduction but address only muscle-related lines. Combining injectable treatments with topical peptide serums could offer a more comprehensive approach to facial rejuvenation. This real-world evidence from multiple experienced clinicians suggests peptide-based skincare may provide additive benefits to standard cosmetic procedures.","specificNumbers":"2% acetyl hexapeptide-8 · 2% dipeptide diaminobutyroyl · 5% PHA · 5% niacinamide · 1% laminaria extract · 7 clinicians · 9 skin biomarkers targeted · Twice daily application","methodology":"Real-world clinical case series from 5 dermatologists and 2 surgeons reporting their experiences using a topical neuropeptide serum (TNP-serum) in combination with botulinum toxin type-A injections. Patients applied the serum twice daily as part of an integrated skincare regimen. This is observational reporting of clinical experience, not a controlled trial.","limitations":"This is a case series based on clinician observations, not a controlled clinical trial. There is no placebo or comparator group, no blinding, and no standardized outcome measures. The number of patients treated is not specified. As a journal supplement article, the publication format raises questions about potential industry sponsorship or influence."},{"rthcId":"RPEP-08782","title":"Cardiovascular event reduction among a US population eligible for semaglutide per the SELECT trial.","authors":"Lusk, Jay B; Glover, LáShauntá; Soneji, Samir; Granger, Christopher B; O'Brien, Emily; Pagidipati, Neha","year":2024,"journal":"American heart journal, 276, 110-114","doi":"10.1016/j.ahj.2024.05.007","pmid":"39182939","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08783","title":"Effects of Semaglutide and Tirzepatide on Bone Metabolism in Type 2 Diabetic Mice.","authors":"Lv, Fang; Cai, Xiaoling; Lin, Chu; Yang, Wenjia; Ji, Linong","year":2024,"journal":"Pharmaceuticals (Basel, Switzerland), 17(12)","doi":"10.3390/ph17121655","pmid":"39770498","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08784","title":"Adherence and persistence among people with type 2 diabetes newly initiating oral semaglutide versus DPP-4is in a US real-world setting.","authors":"Lv, Lei; Brady, Brenna L; Xie, Lin; Guevarra, Mico; Turchin, Alexander","year":2024,"journal":"Primary care diabetes, 18(5), 511-517","doi":"10.1016/j.pcd.2024.06.013","pmid":"38991896","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08785","title":"Comparative efficacy of different drugs in acute heart failure with renal dysfunction: a systematic review and network meta-analysis.","authors":"Lv, Qianyu; Wu, Qian; Yang, Yingtian; Li, Lanlan; Ye, Xuejiao; Wang, Shihan; Lv, Yanfei; Wang, Manshi; Li, Yushan","year":2024,"journal":"Frontiers in cardiovascular medicine, 11, 1444068","doi":"10.3389/fcvm.2024.1444068","pmid":"39877019","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 13 studies (21,745 patients), the network meta-analysis compared nesiritide, dopamine, tolvaptan, levosimendan, dobutamine, furosemide, spirolactone, and high-dose diuretics (HDD).\n\nKey results:\n- HDD had the best efficacy in reducing NT-proBNP levels, with a mean difference of -950.24 (95% CrI: -1,832.21 to -64.12) compared to placebo/conventional treatment.\n- Levosimendan significantly improved GFR compared to placebo (MD = 14.46; 95% CrI: 3.88 to 25.97) and tolvaptan (MD = 13.83; 95% CrI: 2.31 to 25.33).\n- No significant differences were found in 60-day all-cause mortality or cardiovascular mortality across all drugs.\n- Nesiritide did not demonstrate superior efficacy compared to other treatments in this population.","whyItMatters":"Acute heart failure with kidney dysfunction is common and carries high mortality. This analysis provides the first comprehensive network comparison of multiple drug classes in this specific population, helping clinicians identify optimal treatments. The finding that the peptide drug nesiritide did not outperform alternatives is particularly relevant given its cost and prior controversy.","specificNumbers":"","methodology":"This was a systematic review and network meta-analysis searching PubMed, EMBASE, Cochrane Library, and Web of Science for clinical trials of acute heart failure drugs published between 2001 and March 2024. From 30,697 citations screened, 13 studies with 21,745 patients were included. Primary outcomes included NT-proBNP, BNP, GFR, blood urea nitrogen, serum creatinine, 60-day all-cause mortality, and cardiovascular mortality. The study was pre-registered on PROSPERO.","limitations":"The included studies varied in design, drug doses, follow-up periods, and patient populations, which may affect comparisons. The network meta-analysis relies on indirect comparisons for many drug pairs. Only 13 studies met inclusion criteria, and some drug comparisons had limited data. The 60-day mortality endpoint may be too short to capture meaningful survival differences."},{"rthcId":"RPEP-08786","title":"Long-term effects of different hypoglycemic drugs on carotid intima-media thickness progression: a systematic review and network meta-analysis.","authors":"Lv, Qianyu; Yang, Yingtian; Lv, Yanfei; Wu, Qian; Hou, Xinzheng; Li, Lanlan; Ye, Xuejiao; Yang, Chenyan; Wang, Shihan","year":2024,"journal":"Frontiers in endocrinology, 15, 1403606","doi":"10.3389/fendo.2024.1403606","pmid":"38883606","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08787","title":"GLP-1 analogue liraglutide attenuates CIH-induced cognitive deficits by inhibiting oxidative stress, neuroinflammation, and apoptosis via the Nrf2/HO-1 and MAPK/NF-κB signaling pathways.","authors":"Lv, Renjun; Zhao, Yan; Wang, Xiao; He, Yao; Dong, Na; Min, Xiangzhen; Liu, Xueying; Yu, Qin; Yuan, Kai; Yue, Hongmei; Yin, Qingqing","year":2024,"journal":"International immunopharmacology, 142(Pt B), 113222","doi":"10.1016/j.intimp.2024.113222","pmid":"39321702","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08788","title":"Expression and antimicrobial activity of the recombinant bovine lactoferricin in Pichia pastoris.","authors":"Lv, Xueqin; Zhang, Yuting; Wang, Lingrui; Cui, Shixiu; Liu, Yanfeng; Li, Jianghua; Du, Guocheng; Liu, Long","year":2024,"journal":"Synthetic and systems biotechnology, 9(1), 26-32","doi":"10.1016/j.synbio.2023.12.002","pmid":"38221910","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08789","title":"Anti-Obesity Effects of a Collagen with Low Digestibility and High Swelling Capacity: A Human Randomized Control Trial.","authors":"López-Yoldi, Miguel; Riezu-Boj, José I; Abete, Itziar; Ibero-Baraibar, Idoia; Aranaz, Paula; González-Salazar, Itxaso; Izco, Jesús M; Recalde, José I; González-Navarro, Carlos J; Milagro, Fermín I; Zulet, María A","year":2024,"journal":"Nutrients, 16(20)","doi":"10.3390/nu16203550","pmid":"39458544","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08790","title":"Effect of dulaglutide in promoting abstinence during smoking cessation: 12-month follow-up of a single-centre, randomised, double-blind, placebo-controlled, parallel group trial.","authors":"Lüthi, Hualin; Lengsfeld, Sophia; Burkard, Thilo; Meienberg, Andrea; Jeanloz, Nica; Vukajlovic, Tanja; Bologna, Katja; Steinmetz, Michelle; Bathelt, Cemile; Sailer, Clara O; Laager, Mirjam; Vogt, Deborah R; Hemkens, Lars G; Speich, Benjamin; Urwyler, Sandrine A; Kühne, Jill; Baur, Fabienne; Lutz, Linda N; Erlanger, Tobias E; Christ-Crain, Mirjam; Winzeler, Bettina","year":2024,"journal":"EClinicalMedicine, 68, 102429","doi":"10.1016/j.eclinm.2024.102429","pmid":"38371479","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08791","title":"Development of a Double-Stapled Peptide Stabilizing Both α-Helix and β-Sheet Structures for Degrading Transcription Factor AR-V7.","authors":"Ma, Bohan; Liu, Donghua; Zheng, Mengjun; Wang, Zhe; Zhang, Dize; Jian, Yanlin; Ma, Jian; Fan, Yizeng; Chen, Yule; Gao, Yang; Liu, Jing; Li, Xiang; Li, Lei","year":2024,"journal":"JACS Au, 4(2), 816-827","doi":"10.1021/jacsau.3c00795","pmid":"38425893","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08792","title":"A photo-modulated nitric oxide delivering hydrogel for the accelerated healing of biofilm infected chronic wounds.","authors":"Ma, Huifang; Wang, Tengjiao; Li, Gangfeng; Liang, Jiaheng; Zhang, Jianhong; Liu, Yang; Zhong, Wenbin; Li, Peng","year":2024,"journal":"Acta biomaterialia, 188, 169-183","doi":"10.1016/j.actbio.2024.09.017","pmid":"39299622","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The DEPN hydrogel demonstrated a three-stage nitric oxide release strategy: continuous slow release to disperse biofilms, laser-triggered rapid burst release (with photothermal heating) to eliminate pathogens, and sustained slow release to promote tissue remodeling. The hydrogel effectively eliminated a broad spectrum of drug-resistant Gram-positive bacteria, Gram-negative bacteria, and fungal biofilms through synergistic effects of NO, photothermal therapy, and the antimicrobial peptide ε-poly-lysine.\n\nIn vitro, the hydrogel promoted proliferation of mouse fibroblasts and migration of endothelial cells. In vivo, it achieved exceptional therapeutic outcomes in mice with MRSA-infected diabetic wounds by eliminating biofilm infection, regulating inflammation, facilitating angiogenesis, and promoting collagen deposition — addressing the multiple barriers that prevent chronic wound healing.","whyItMatters":"Chronic wounds affect millions worldwide, with diabetic foot ulcers alone costing healthcare systems billions annually. Drug-resistant biofilm infections make these wounds extremely difficult to treat with conventional antibiotics. This peptide-based hydrogel addresses multiple wound healing barriers simultaneously — killing resistant bacteria, breaking up protective biofilms, controlling inflammation, and promoting tissue repair — offering a potential solution for wounds that currently have few effective treatments.","specificNumbers":"","methodology":"The hydrogel was constructed via Schiff-base crosslinking of oxidized dextran with the antimicrobial peptide ε-poly-lysine, with encapsulated photothermal nanoparticles carrying a nitric oxide donor. In vitro testing assessed biofilm dispersal, fibroblast proliferation, and endothelial cell migration. Antimicrobial activity was tested against drug-resistant Gram-positive/negative bacteria and fungi. In vivo efficacy was evaluated in a diabetic mouse wound model infected with methicillin-resistant Staphylococcus aureus (MRSA), with assessment of infection clearance, inflammation, angiogenesis, and collagen deposition.","limitations":"All experiments were conducted in mice, and wound healing in mice differs significantly from humans in skin structure and immune response. The diabetic wound model was artificially induced and may not fully replicate the complexity of human diabetic wounds. Long-term safety of the photothermal nanoparticles was not assessed. The need for NIR laser equipment adds complexity and cost that could limit clinical adoption. Specific quantitative data on wound closure rates were not provided in the abstract."},{"rthcId":"RPEP-08793","title":"Effect of Food Consumption on the Pharmacokinetics, Safety, and Tolerability of Once-Daily Orally Administered Orforglipron (LY3502970), a Non-peptide GLP-1 Receptor Agonist.","authors":"Ma, Xiaosu; Liu, Rong; Pratt, Edward J; Benson, Charles T; Bhattachar, Shobha N; Sloop, Kyle W","year":2024,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 15(4), 819-832","doi":"10.1007/s13300-024-01554-1","pmid":"38402332","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08794","title":"Spotlight on HIV-derived TAT peptide as a molecular shuttle in drug delivery.","authors":"Maani, Zahra; Rahbarnia, Leila; Bahadori, Ali; Chollou, Khalil Maleki; Farajnia, Safar","year":2024,"journal":"Drug discovery today, 29(11), 104191","doi":"10.1016/j.drudis.2024.104191","pmid":"39322176","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08795","title":"Gut hormone analogues and skeletal health in diabetes and obesity: Evidence from preclinical models.","authors":"Mabilleau, Guillaume; Bouvard, Béatrice","year":2024,"journal":"Peptides, 177, 171228","doi":"10.1016/j.peptides.2024.171228","pmid":"38657908","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08796","title":"Pain persists in mice lacking both Substance P and CGRPα signaling.","authors":"MacDonald, Donald Iain; Jayabalan, Monessha; Seaman, Jonathan; Balaji, Rakshita; Nickolls, Alec; Chesler, Alexander","year":2024,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2023.11.15.567208","pmid":"38076807","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Mice genetically lacking both Substance P (Tac1 knockout) and CGRPα (Calca knockout) — two neuropeptides long considered central to pain transmission — displayed largely intact pain responses across every type of pain tested. Mechanical, thermal, chemical, and visceral pain were all preserved. Chronic inflammatory pain and neurogenic inflammation were unaffected. Even neuropathic pain from nerve injury or chemotherapy treatment persisted normally.\n\nBoth peptides were confirmed completely absent throughout the nervous system, eliminating the possibility of residual signaling. This definitively shows that even combined loss of these two major pain-associated neuropeptides is not sufficient to block pain transmission.","whyItMatters":"Substance P and CGRP have been the two most prominent neuropeptide targets for pain treatment for decades. Billions of dollars were spent developing drugs targeting each individually, and both failed as pain treatments in clinical trials. The prevailing hypothesis was that their co-expression meant both needed to be blocked simultaneously. This study demolishes that hypothesis — even eliminating both completely doesn't stop pain. This fundamentally reshapes our understanding of pain neurobiology and redirects the search for pain targets away from these neuropeptides.","specificNumbers":"2 neuropeptides eliminated (Substance P + CGRPα) · Both undetectable throughout nervous system · Normal responses in mechanical, thermal, chemical, visceral pain · Inflammatory pain intact · Neuropathic pain intact · Itch intact","methodology":"Researchers generated Tac1/Calca double knockout (DKO) mice lacking both Substance P and CGRPα. Complete peptide absence was confirmed throughout the nervous system. Pain behavior was assessed using a comprehensive battery: mechanical stimuli, thermal stimuli, chemical irritants, visceral pain models, itch assays, chronic inflammatory pain, neurogenic inflammation, nerve injury-induced neuropathic pain, and chemotherapy-induced neuropathic pain.","limitations":"This is a preprint (bioRxiv), not yet peer-reviewed. Genetic knockouts from birth may allow compensatory mechanisms to develop that mask the peptides' roles in normally functioning adults. CGRPβ (from the Calcb gene) was not eliminated and could provide partial compensation. The study cannot address whether acute pharmacological blockade of both peptides in adult animals would have different results than lifelong genetic absence. Mouse pain models may not fully recapitulate human pain experiences."},{"rthcId":"RPEP-08797","title":"Cross-species evidence for a developmental origin of adult hypersomnia with loss of synaptic adhesion molecules beat-Ia/CADM2.","authors":"Mace, Kyla; Zimmerman, Amber; Chesi, Alessandra; Doldur-Balli, Fusun; Kim, Hayle; Almeraya Del Valle, Erika; Pack, Allan I; Grant, Struan F A; Kayser, Matthew S","year":2024,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2024.09.25.615048","pmid":"39386457","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08798","title":"Glucagon-like peptide-1 receptor agonists and kidney outcomes.","authors":"MacIsaac, Richard J; Trevella, Philippa; Ekinci, Elif I","year":2024,"journal":"Journal of diabetes, 16(10), e13609","doi":"10.1111/1753-0407.13609","pmid":"39364792","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08799","title":"Sex differences in expression of CGRP family of receptors and ligands in the rat trigeminal system.","authors":"Maddahi, Aida; Edvinsson, Jacob C A; Edvinsson, Lars","year":2024,"journal":"The journal of headache and pain, 25(1), 193","doi":"10.1186/s10194-024-01893-1","pmid":"39516766","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08800","title":"Defatted Wheat Germ Protein-Derived Peptides Showed Multiple Biological Activities from the Stomach to Small Intestine: In Silico and In Vitro Approaches.","authors":"Madhavi, Bolappa Gamage Kaushalya; Wijethunga, Anushi Madushani; Okagu, Ogadimma D; Sun, Xiaohong","year":2024,"journal":"Journal of agricultural and food chemistry, 72(37), 20527-20536","doi":"10.1021/acs.jafc.4c06539","pmid":"39231371","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08801","title":"Glucagon-like peptide-1 agonists in cardiovascular diseases: a bibliometric analysis from inception to 2023.","authors":"Mahapatro, Abinash; Bozorgi, Ali; Obulareddy, Sri U J; Jain, Shika M; Reddy Korsapati, Rohan; Kumar, Aroon; Patel, Kristina; Soltani Moghadam, Saman; Arya, Arash; Jameel Alotaibi, Abdulhadi; Keivanlou, Mohammad-Hossein; Hassanipour, Soheil; Hasanpour, Maryam; Amini-Salehi, Ehsan","year":2024,"journal":"Annals of medicine and surgery (2012), 86(11), 6602-6618","doi":"10.1097/MS9.0000000000002592","pmid":"39525800","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08802","title":"The Effects of Tirzepatide on Lipid Profile: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.","authors":"Mahar, Muhammad Umar; Mahmud, Omar; Ahmed, Salaar; Qureshi, Saleha Ahmed; Kakar, Wasila Gul; Fatima, Syeda Sadia","year":2024,"journal":"Journal of obesity & metabolic syndrome, 33(4), 348-359","doi":"10.7570/jomes24008","pmid":"39681390","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Pooled analysis of 13 randomized controlled trials demonstrated that tirzepatide significantly improved all measured lipid markers, including cholesterol and triglycerides. Key findings:\n\n- All lipid markers improved with tirzepatide treatment\n- A clear dose-response relationship was observed: 5 mg, 10 mg, and 15 mg doses showed progressively greater improvements\n- Tirzepatide appeared superior to conventional agents including insulin formulations and traditional GLP-1 agonists for metabolic improvement\n- Of 13 included trials, 9 had low risk of bias, 2 moderate, and 2 high risk of bias","whyItMatters":"Abnormal cholesterol and triglyceride levels are major risk factors for heart disease — the leading cause of death worldwide. Patients with type 2 diabetes and obesity often have elevated lipids, compounding their cardiovascular risk. This meta-analysis shows that tirzepatide addresses lipid abnormalities in addition to its established benefits for blood sugar and weight, making it a potentially comprehensive metabolic therapy that could reduce the need for separate cholesterol-lowering medications.","specificNumbers":"","methodology":"Systematic review and meta-analysis following standard methodology. PubMed and ClinicalTrials.gov were searched for randomized controlled trials of tirzepatide reporting lipid outcomes. From 433 initial records, 18 underwent full-text review and 14 articles (reporting 13 RCTs) were included. Two independent reviewers screened and extracted data, with conflicts resolved by consensus. Risk of bias was assessed. Meta-analysis used an inverse variance random-effects model.","limitations":"The specific magnitude of lipid improvements (percent changes, absolute values) is not detailed in the abstract. Two of the 13 included trials had a high risk of bias. The duration of trials and patient populations varied across studies. The analysis does not separate effects in diabetic versus non-diabetic populations. Whether the lipid improvements translate to reduced cardiovascular events is not addressed by this meta-analysis. Publication bias was not explicitly discussed in the abstract."},{"rthcId":"RPEP-08803","title":"Calming the Nerves via the Immune Instructive Physiochemical Properties of Self-Assembling Peptide Hydrogels.","authors":"Mahmoudi, Negar; Mohamed, Elmira; Dehnavi, Shiva Soltani; Aguilar, Lilith M Caballero; Harvey, Alan R; Parish, Clare L; Williams, Richard J; Nisbet, David R","year":2024,"journal":"Advanced science (Weinheim, Baden-Wurttemberg, Germany), 11(5), e2303707","doi":"10.1002/advs.202303707","pmid":"38030559","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08804","title":"Retinopathy risk factors in patients with type 2 diabetes on liraglutide.","authors":"Mahzari, Moeber M; Alanazy, Abdulmalik M; Feroz, Zeeshan; Almani, Khalid M; Alghamdi, Meshari A; Almadani, Abdulaziz S; Alzahrani, Majed K; Alibrahim, Ahmed R; Badri, Motasim","year":2024,"journal":"Medicine, 103(29), e39026","doi":"10.1097/MD.0000000000039026","pmid":"39029073","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"After a median 2-year follow-up of 181 patients on liraglutide:\n\n• 81.6% of patients (71/87) without retinopathy at baseline remained retinopathy-free\n• Among patients with retinopathy at baseline: 25.5% improved, 44.7% showed no change\n• Both HbA1c and weight decreased significantly (P<0.001)\n• Independent risk factors for retinopathy were: insulin use (OR 2.68), hypertension (OR 2.56), higher HbA1c (OR 1.17 per unit), older age (OR 1.03 per year), and longer diabetes duration (OR 1.04 per year)\n• Liraglutide itself was not identified as a retinopathy risk factor\n\nBaseline characteristics: mean age 58.2 years, 72.9% female, median diabetes duration 19 years, median baseline HbA1c 9%, 69.6% on insulin.","whyItMatters":"Semaglutide's SUSTAIN-6 trial raised alarm when it showed increased retinopathy events, creating concern about the entire GLP-1 drug class. This study provides real-world data from the Middle East — a region with high diabetes prevalence — showing liraglutide does not appear to worsen retinopathy. This is particularly important for clinicians in regions where diabetes is common and retinopathy screening may be less accessible.","specificNumbers":"","methodology":"Retrospective cohort study at King Abdulaziz Medical City, Riyadh, Saudi Arabia. Included patients aged ≥14 years with type 2 diabetes treated with liraglutide between 2015 and 2021 who had documented retinopathy assessments at baseline and follow-up. Data collected included demographics, retinopathy status, BMI, and HbA1c at baseline and follow-up. Multivariate binary mixed effect analysis was used to identify retinopathy risk factors.","limitations":"Retrospective design without a control group limits causal conclusions. The study was conducted at a single center in Saudi Arabia, limiting generalizability. Retinopathy assessment methods and frequency were not standardized. The median baseline HbA1c of 9% indicates poorly controlled diabetes, which may not represent the broader liraglutide-treated population. Relatively small sample size (181 patients) limits power to detect small retinopathy risks."},{"rthcId":"RPEP-08805","title":"Phenogroups and Their Prognosis of Acute Decompensated Heart Failure with Preserved Ejection Fraction.","authors":"Makino, Taro; Ishihara, Yuya; Harada, Masahide; Sobue, Yoshihiro; Watanabe, Eiichi; Ozaki, Yukio; Izawa, Hideo","year":2024,"journal":"International heart journal, 65(5), 841-848","doi":"10.1536/ihj.24-080","pmid":"39261030","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08806","title":"Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity.","authors":"Malhotra, Atul; Grunstein, Ronald R; Fietze, Ingo; Weaver, Terri E; Redline, Susan; Azarbarzin, Ali; Sands, Scott A; Schwab, Richard J; Dunn, Julia P; Chakladar, Sujatro; Bunck, Mathijs C; Bednarik, Josef","year":2024,"journal":"The New England journal of medicine, 391(13), 1193-1205","doi":"10.1056/NEJMoa2404881","pmid":"38912654","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08807","title":"Peptide-Oligonucleotide Conjugation: Chemistry and Therapeutic Applications.","authors":"Malinowska, Anna L; Huynh, Harley L; Bose, Sritama","year":2024,"journal":"Current issues in molecular biology, 46(10), 11031-11047","doi":"10.3390/cimb46100655","pmid":"39451535","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08808","title":"Cancer-oocyte SAS1B protein is expressed at the cell surface of multiple solid tumors and targeted with antibody-drug conjugates.","authors":"Mandal, Arabinda; Shetty, Jagathpala; Tran, Christine A; Olson, Walter C; Mandal, Mriganka; Ban, Bhupal; Pires, Eusebio S; Adair, Sara J; Bauer, Todd W; Slingluff, Craig L; Herr, John C","year":2024,"journal":"Journal for immunotherapy of cancer, 12(3)","doi":"10.1136/jitc-2023-008430","pmid":"38485187","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08809","title":"Acute Pancreatitis Caused by Tirzepatide.","authors":"Mando, Nur; Thomson, Erica; Fowler, Matthew; Short, Lillian; Gillen, Nora","year":2024,"journal":"Cureus, 16(12), e76007","doi":"10.7759/cureus.76007","pmid":"39834977","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08810","title":"Effects of semaglutide with and without concomitant SGLT2 inhibitor use in participants with type 2 diabetes and chronic kidney disease in the FLOW trial.","authors":"Mann, Johannes F E; Rossing, Peter; Bakris, George; Belmar, Nicolas; Bosch-Traberg, Heidrun; Busch, Robert; Charytan, David M; Hadjadj, Samy; Gillard, Pieter; Górriz, José Luis; Idorn, Thomas; Ji, Linong; Mahaffey, Kenneth W; Perkovic, Vlado; Rasmussen, Søren; Schmieder, Roland E; Pratley, Richard E; Tuttle, Katherine R","year":2024,"journal":"Nature medicine, 30(10), 2849-2856","doi":"10.1038/s41591-024-03133-0","pmid":"38914124","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08811","title":"GLP-1 Agonists Can Affect Mood: A Case of Worsened Depression on Ozempic (Semaglutide).","authors":"Manoharan, Senthil Vel Rajan Rajaram; Madan, Rohit","year":2024,"journal":"Innovations in clinical neuroscience, 21(4-6), 25-26","doi":null,"pmid":"38938530","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08812","title":"Are glucagon-like peptide-1 receptor agonists anti-consummatory drugs?","authors":"Mansur, Rodrigo B; Di Vincenzo, Joshua D; Badulescu, Sebastian; Gill, Hartej; Tabassum, Aniqa; López, Cristian Llach; Rosenblat, Joshua D; McIntyre, Roger S","year":2024,"journal":"CNS spectrums, 29(6), 536-541","doi":"10.1017/S109285292400244X","pmid":"39801083","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08813","title":"Peptosome: A New Efficient Transfection Tool as an Alternative to Liposome.","authors":"Manteghi, Maliheh; Can, Ozge; Kocagoz, Tanil","year":2024,"journal":"International journal of molecular sciences, 25(13)","doi":"10.3390/ijms25136918","pmid":"39000028","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08814","title":"The Pathologic Roles and Therapeutic Implications of Ghrelin/GHSR System in Mental Disorders.","authors":"Mao, Qianshuo; Wang, Jinjia; Yang, Zihan; Ding, Ruidong; Lv, Shuangyu; Ji, Xinying","year":2024,"journal":"Depression and anxiety, 2024, 5537319","doi":"10.1155/2024/5537319","pmid":"40226675","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08815","title":"Nanocomposite Hydrogels from Nanodiamonds and a Self-Assembling Tripeptide.","authors":"Marin, Davide; Kralj, Slavko; Stehlik, Stepan; Marchesan, Silvia","year":2024,"journal":"Chemistry (Weinheim an der Bergstrasse, Germany), 30(70), e202402961","doi":"10.1002/chem.202402961","pmid":"39325557","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08816","title":"Role of Brown Adipose Tissue in Metabolic Health and Efficacy of Drug Treatment for Obesity.","authors":"Markina, Natalia O; Matveev, Georgy A; Zasypkin, German G; Golikova, Tatiana I; Ryzhkova, Daria V; Kononova, Yulia A; Danilov, Sergey D; Babenko, Alina Yu","year":2024,"journal":"Journal of clinical medicine, 13(14)","doi":"10.3390/jcm13144151","pmid":"39064191","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08817","title":"A nanoparticle platform for combined mucosal healing and immunomodulation in inflammatory bowel disease treatment.","authors":"Marotti, Valentina; Xu, Yining; Bohns Michalowski, Cécilia; Zhang, Wunan; Domingues, Inês; Ameraoui, Hafsa; Moreels, Tom G; Baatsen, Pieter; Van Hul, Matthias; Muccioli, Giulio G; Cani, Patrice D; Alhouayek, Mireille; Malfanti, Alessio; Beloqui, Ana","year":2024,"journal":"Bioactive materials, 32, 206-221","doi":"10.1016/j.bioactmat.2023.09.014","pmid":"37859689","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08818","title":"Efficacy and Safety in a Real-World Study of the New Oral Formulation of Semaglutide in Patients with Chronic Kidney Disease and Type 2 Diabetes Mellitus.","authors":"Marques Vidas, María; López-Sánchez, Paula; Sánchez-Briales, Paula; López Illazquez, María Victoria; Portolés, Jose","year":2024,"journal":"Journal of clinical medicine, 13(17)","doi":"10.3390/jcm13175166","pmid":"39274378","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08819","title":"GLP-1 Analogue-Loaded Glucose-Responsive Nanoparticles as Allies of Stem Cell Therapies for the Treatment of Type I Diabetes.","authors":"Marques, Joana Moreira; Nunes, Rute; Carvalho, Ana Margarida; Florindo, Helena; Ferreira, Domingos; Sarmento, Bruno","year":2024,"journal":"ACS pharmacology & translational science, 7(5), 1650-1663","doi":"10.1021/acsptsci.4c00173","pmid":"38751616","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08820","title":"Absorption, distribution, metabolism, and excretion of tirzepatide in humans, rats, and monkeys.","authors":"Martin, Jennifer A; Czeskis, Boris; Urva, Shweta; Cassidy, Kenneth C","year":2024,"journal":"European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 202, 106895","doi":"10.1016/j.ejps.2024.106895","pmid":"39243911","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08821","title":"Antioxidant and Angiotensin-Converting Enzyme Inhibitory Activity of Faba Bean-Derived Peptides After In Vitro Gastrointestinal Digestion: Insight into Their Mechanism of Action.","authors":"Martineau-Côté, Delphine; Achouri, Allaoua; Karboune, Salwa; L'Hocine, Lamia","year":2024,"journal":"Journal of agricultural and food chemistry, 72(12), 6432-6443","doi":"10.1021/acs.jafc.4c00829","pmid":"38470110","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Of 11 synthesized faba bean-derived peptides:\n\nAntioxidant activity (7 peptides):\n- TETWNPNHPEL showed the highest activity: ABTS EC50 = 0.5 ± 0.2 mM; DPPH EC50 = 2.1 ± 0.1 mM\n- Other active peptides: NYDEGSEPR, TETWNPNHPE, VIPTEPPH, VIPTEPPHA, VVIPTEPPHA, VVIPTEPPH\n\nACE inhibitory activity (4 peptides):\n- TETWNPNHPEL: IC50 = 43 ± 1 μM (most potent)\n- VVIPTEPPHA: IC50 = 50 ± 5 μM\n- TETWNPNHPE: IC50 = 90 ± 10 μM\n- VIPTEPPHA: IC50 = 123 ± 5 μM\n\nKinetic studies and molecular docking confirmed all ACE-inhibitory peptides act through a noncompetitive mechanism — they bind to a site other than the enzyme's active site.","whyItMatters":"High blood pressure affects over a billion people worldwide, and ACE inhibitor drugs are among the most prescribed medications. Finding natural food-derived peptides with ACE-inhibitory activity could lead to functional foods or supplements that help manage blood pressure with fewer side effects than synthetic drugs. The dual activity — both antioxidant and ACE-inhibitory — in the same peptides makes them particularly interesting for cardiovascular health, since oxidative stress and hypertension are closely linked.","specificNumbers":"","methodology":"Faba bean flour was subjected to in vitro gastrointestinal digestion (simulating stomach and intestinal conditions). Eleven peptides identified from the digest were chemically synthesized for individual testing. Antioxidant activity was measured using ABTS and DPPH radical scavenging assays. ACE inhibitory activity was quantified by IC50 values. Enzyme kinetic studies determined the inhibition mechanism (competitive vs. noncompetitive). Molecular docking simulations modeled how the peptides interact with the ACE enzyme.","limitations":"All testing was performed in vitro — digestion was simulated, not actual human digestion, and ACE inhibition was measured in a test tube, not in human blood vessels. The IC50 values (43-123 μM) need to be evaluated in the context of achievable plasma concentrations after oral consumption, which is typically much lower. Many food-derived ACE-inhibitory peptides lose activity after absorption or further metabolism. No animal or human blood pressure studies were conducted. The peptide sequences were identified from a simulated digest and may not represent the exact peptides released during actual human digestion."},{"rthcId":"RPEP-08822","title":"Potential role of glucagon-like peptide-1 (GLP-1) receptor agonists in substance use disorder: A systematic review of randomized trials.","authors":"Martinelli, Silvia; Mazzotta, Alessandro; Longaroni, Mattia; Petrucciani, Niccolò","year":2024,"journal":"Drug and alcohol dependence, 264, 112424","doi":"10.1016/j.drugalcdep.2024.112424","pmid":"39288591","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"From an initial screen of 1,218 studies, only 5 randomized trials met the inclusion criteria, incorporating 630 total participants treated with exenatide (3 studies) or dulaglutide (2 studies).\n\nOf the five studies assessing therapeutic effects on substance use disorders, three demonstrated a significant decrease in substance use, specifically for alcohol and nicotine. Three studies also reported on metabolic outcomes, showing notable reductions in body weight, BMI, and HbA1c in the GLP-1 receptor agonist-treated groups.","whyItMatters":"Substance use disorders are notoriously difficult to treat, with high relapse rates and limited pharmacological options. The finding that GLP-1 receptor agonists — drugs already widely prescribed and well-characterized — may reduce alcohol and nicotine use opens an exciting new therapeutic avenue. GLP-1 receptors are present in brain reward circuits, providing a biological rationale for why these drugs might dampen addictive behaviors alongside their metabolic effects.","specificNumbers":"","methodology":"Systematic review following PRISMA guidelines. Researchers searched MEDLINE, Scopus, and Cochrane Library for randomized clinical trials of GLP-1 receptor agonists in patients diagnosed with substance use disorders. The primary outcome was the therapeutic effect on substance use disorder; secondary outcomes included weight, BMI, and HbA1c changes. From 1,218 initial results, 507 passed title/abstract screening, and 5 met full inclusion criteria.","limitations":"Only five trials met inclusion criteria, making the evidence base very small. The total of 630 participants limits statistical power. Only two GLP-1 receptor agonists (exenatide and dulaglutide) were studied — newer drugs like semaglutide were not included. The review could not perform a meta-analysis due to heterogeneity. Two of five studies did not show significant effects. The studies focused on alcohol and nicotine — other substance use disorders were not represented."},{"rthcId":"RPEP-08823","title":"Effect of preoperative liraglutide 3.0 mg on incidence of intraoperative adhesions in laparoscopic sleeve gastrectomy.","authors":"Martines, G; Giove, C; Carlucci, B; Dezi, A; Ranieri, C; Rotelli, M T; De Fazio, M; Tomasicchio, G","year":2024,"journal":"Surgical endoscopy, 38(12), 7152-7157","doi":"10.1007/s00464-024-11231-w","pmid":"39347961","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08824","title":"SGLT2i and GLP1-RA exert additive cardiorenal protection with a RAS blocker in uninephrectomized db/db mice.","authors":"Martos-Guillami, Nerea; Vergara, Ander; Llorens-Cebrià, Carmen; Motto, Aku Enam; Martínez-Díaz, Irene; Gonçalves, Francisco; Garcias-Ramis, Maria Magdalena; Allo-Urzainqui, Estibaliz; Narváez, Alonso; Bermejo, Sheila; Muñoz, Vicent; León-Román, Juan; Ferrer-Costa, Roser; Jacobs-Cachá, Conxita; Vilardell-Vilà, Jordi; Soler, María José","year":2024,"journal":"Frontiers in pharmacology, 15, 1415879","doi":"10.3389/fphar.2024.1415879","pmid":"39434906","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08825","title":"Anti-Inflammatory and Antioxidant Properties of a New Mixture of Vitamin C, Collagen Peptides, Resveratrol, and Astaxanthin in Tenocytes: Molecular Basis for Future Applications in Tendinopathies.","authors":"Marzagalli, Monica; Battaglia, Stefania; Raimondi, Michela; Fontana, Fabrizio; Cozzi, Marco; Ranieri, Francesca R; Sacchi, Roberto; Curti, Valeria; Limonta, Patrizia","year":2024,"journal":"Mediators of inflammation, 2024, 5273198","doi":"10.1155/2024/5273198","pmid":"39108992","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08826","title":"Blood pressure monitoring in elderly migraineurs starting an anti-CGRP monoclonal antibody: a real-world prospective study.","authors":"Mascarella, Davide; Andrini, Giorgia; Baraldi, Carlo; Altamura, Claudia; Favoni, Valentina; Lo Castro, Flavia; Pierangeli, Giulia; Vernieri, Fabrizio; Guerzoni, Simona; Cevoli, Sabina","year":2024,"journal":"Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 45(11), 5365-5373","doi":"10.1007/s10072-024-07567-9","pmid":"38795273","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08827","title":"Safe Continuation of Glucagon-like Peptide 1 Receptor Agonists at Endoscopy: A Case Series of 57 Adults Undergoing Endoscopic Sleeve Gastroplasty.","authors":"Maselli, Daniel B; Lee, Daniel; Bi, Danse; Jirapinyo, Pichamol; Thompson, Christopher C; Donnangelo, Lauren L; McGowan, Christopher E","year":2024,"journal":"Obesity surgery, 34(7), 2369-2374","doi":"10.1007/s11695-024-07278-2","pmid":"38753265","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 57 consecutive adults on GLP-1 RAs (45.6% semaglutide, 22.8% dulaglutide, 19.3% liraglutide, 12.3% tirzepatide) who underwent ESG without drug interruption:\n- Zero instances of retained gastric solids\n- Zero cases of pulmonary aspiration\n- Zero cases of gastroesophageal regurgitation\n- Zero episodes of hypoxia during intubation, endoscopy, or recovery\n\nAll patients followed a standardized preparation: liquid-only diet for ≥24 hours and nil per os for ≥12 hours before the procedure. The 100% safety record across multiple GLP-1 drugs and across three centers supports the adequacy of this fasting protocol.","whyItMatters":"Millions of patients on GLP-1 drugs need endoscopic and surgical procedures, and the question of whether to stop these medications has caused significant clinical confusion and patient anxiety. Stopping GLP-1 drugs can lead to blood sugar destabilization and weight regain. This study provides the first substantial case series evidence that continuing GLP-1 drugs may be safe with an appropriate extended fasting protocol, potentially simplifying procedural planning for millions of patients.","specificNumbers":"","methodology":"Retrospective case series reviewing all patients who underwent endoscopic sleeve gastroplasty while on uninterrupted GLP-1 RAs at three centers from August 2022 to February 2024. Patient records, procedure reports, and procedural videos were reviewed for retained gastric products and serious adverse events. All patients followed a standardized pre-procedure protocol (24-hour liquid diet, 12-hour complete fast).","limitations":"This is a retrospective case series without a control group, making it impossible to compare outcomes with patients who did stop their GLP-1 drugs. The sample size (57 patients) is relatively small for detecting rare adverse events. All patients had native gastric anatomy — results may not apply to patients with prior gastric surgery. The extended fasting protocol (24-hour liquid diet) is more conservative than standard fasting and may not be practical for all procedure types. The case series was not designed to detect subclinical retained gastric contents."},{"rthcId":"RPEP-08828","title":"What is known about the use of weight loss medication in women with overweight/obesity on fertility and reproductive health outcomes? A scoping review.","authors":"Maslin, Kate; Alkutbe, Rabab; Gilbert, Jeremy; Pinkney, Jonathan; Shawe, Jill","year":2024,"journal":"Clinical obesity, 14(6), e12690","doi":"10.1111/cob.12690","pmid":"38951960","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08829","title":"Use of Calcitonin Gene-Related Peptide Monoclonal Antibodies for the Treatment of Migraines in Individuals With Multiple Sclerosis.","authors":"Mason, Ashley; Fragapane, Lauren; Toledo-Nieves, Zuleyma; Moreo, Natalie; Aungst, Angela; Robertson, Derrick; Maldonado, Janice","year":2024,"journal":"International journal of MS care, 26(3), 104-107","doi":"10.7224/1537-2073.2023-013","pmid":"38765303","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08830","title":"Label-free quantitative proteomic profiling reveals differential plasma protein expression in patients with obesity after treatment with liraglutide.","authors":"Masood, Afshan; Benabdelkamel, Hicham; Joy, Salini Scaria; Alhossan, Abdulaziz; Alsuwayni, Bashayr; Abdeen, Ghalia; Aldhwayan, Madhawi; Alfadda, Nora A; Miras, Alexander Dimitri; Alfadda, Assim A","year":2024,"journal":"Frontiers in molecular biosciences, 11, 1458675","doi":"10.3389/fmolb.2024.1458675","pmid":"39324112","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Treatment with liraglutide 3 mg for three months significantly altered the plasma protein profile in patients with obesity. Of 151 dysregulated proteins, 31 were upregulated and 120 downregulated. Proteins involved in inflammation and oxidative stress were decreased, while those involved in glycolytic/lipolytic metabolism and cytoskeletal/endothelial reorganization increased. Top potential biomarkers (AUC 0.999) included upregulated Cystatin-B, major vault protein, and plastin-3, and downregulated multimerin-2, large ribosomal P2, and proline-rich acidic protein 1. Key affected pathways centered around MAPK, AKT, and PKc signaling.","whyItMatters":"While liraglutide's weight loss effects are well established, this study reveals the molecular machinery behind those benefits. The shift from inflammatory/oxidative stress proteins toward metabolic and cellular reorganization proteins provides a deeper understanding of how this GLP-1 peptide drug improves overall metabolic health beyond just appetite suppression and weight loss.","specificNumbers":"n=20 · BMI 40.65 ± 3.7 kg/m² · 151 dysregulated proteins · 31 upregulated · 120 downregulated · top biomarkers AUC 0.999 · p<0.001 for weight, BMI, HbA1c changes · 3-month treatment","methodology":"A single-center prospective study enrolled 20 patients with obesity (7 male, 13 female). Blood samples were collected before and after 3 months of liraglutide 3 mg treatment. Label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used for untargeted proteomic profiling. Differentially expressed proteins were identified and analyzed using bioinformatics, ROC curves for biomarker evaluation, and ingenuity pathway analysis (IPA) for network pathway identification.","limitations":"The sample size of 20 patients is small, limiting generalizability. The study was single-center with no control group (before/after design only). Three months of treatment may not capture longer-term proteomic changes. The study measured plasma proteins, which may not fully reflect tissue-level molecular changes. Proteomic findings are exploratory and require validation in larger cohorts."},{"rthcId":"RPEP-08831","title":"Effects of amyloid-β-mimicking peptide hydrogel matrix on neuronal progenitor cell phenotype.","authors":"Mathes, Tess Grett; Monirizad, Mahsa; Ermis, Menekse; de Barros, Natan Roberto; Rodriguez, Marco; Kraatz, Heinz-Bernhard; Jucaud, Vadim; Khademhosseini, Ali; Falcone, Natashya","year":2024,"journal":"Acta biomaterialia, 183, 89-100","doi":"10.1016/j.actbio.2024.05.020","pmid":"38801867","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08832","title":"Outcome of 177Lu-DOTATATE Peptide Receptor Radionuclide Therapy in Progressive Metastatic Neuroendocrine Tumors from a Tertiary Care Center.","authors":"Mathew, David; Sunny, Saumya S; Benjamin, Justin; John, Junita R; Jebasingh, Felix K; Georgy, Josh T; Singh, Ashish; Oommen, Regi","year":2024,"journal":"Indian journal of endocrinology and metabolism, 28(6), 601-610","doi":"10.4103/ijem.ijem_372_23","pmid":"39881767","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08833","title":"AJICAP-M: Traceless Affinity Peptide Mediated Conjugation Technology for Site-Selective Antibody-Drug Conjugate Synthesis.","authors":"Matsuda, Yutaka; Shikida, Natsuki; Hatada, Noriko; Yamada, Kei; Seki, Takuya; Nakahara, Yuichi; Endo, Yuta; Shimbo, Kazutaka; Takahashi, Kazutoshi; Nakayama, Akira; Mendelsohn, Brian A; Fujii, Tomohiro; Okuzumi, Tatsuya; Hirasawa, Shigeo","year":2024,"journal":"Organic letters, 26(27), 5597-5601","doi":"10.1021/acs.orglett.4c00878","pmid":"38639400","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"AJICAP-M is a traceless site-selective conjugation method that uses Fc-affinity peptides to attach drugs to native (unmodified) antibodies at specific lysine residues (Lys248 or Lys288). The technology produces antibody-drug conjugates with:\n\n- Consistent drug-to-antibody ratios\n- Enhanced stability compared to traditional ADCs\n- Superior in vivo stability demonstrated in comparative animal studies\n- Compatibility with continuous-flow manufacturing — a first for site-selective ADC production\n\nThe \"traceless\" aspect means the affinity peptide is removed after conjugation, leaving no foreign material on the final product.","whyItMatters":"ADCs are one of the fastest-growing classes of cancer drugs, with over a dozen approved. Manufacturing consistency and stability remain major challenges. AJICAP-M's peptide-guided approach could make ADC production more reliable, potentially improving drug efficacy and reducing manufacturing costs.","specificNumbers":"","methodology":"The researchers developed Fc-affinity peptides that temporarily bind to antibodies and direct drug conjugation to specific lysine residues. After drug attachment, the peptide is removed. The resulting ADCs were characterized for drug-to-antibody ratio consistency and stability. In vivo experiments in animals compared AJICAP-M ADC stability to traditional ADCs. The technology was also demonstrated in continuous-flow manufacturing.","limitations":"The abstract does not provide detailed comparative data on stability improvements or specific drug-to-antibody ratios achieved. Only two conjugation sites (Lys248, Lys288) were demonstrated. Clinical data with AJICAP-M-produced ADCs was not presented. The technology's compatibility with different antibody isotypes and drug payloads beyond those tested remains to be fully characterized."},{"rthcId":"RPEP-08834","title":"Neuropeptide Y and Derivates Are Not Ready for Prime Time in Prostate Cancer Early Detection.","authors":"Maurer, Jonathan; Eugster, Philippe J; Collins, Kiana; Vocat, Céline; Oke, Jason; Nicholson, Brian; Rakauskas, Arnas; Grouzmann, Eric; Valerio, Massimo","year":2024,"journal":"European urology open science, 66, 12-15","doi":"10.1016/j.euros.2024.06.008","pmid":"39027656","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Using liquid chromatography tandem mass spectrometry — a highly specific measurement technique — the researchers analyzed NPY, its precursors, and metabolites in plasma and tissue from 181 patients. NPY and related peptides were less accurate than PSA alone at diagnosing significant prostate cancer.\n\nCombining multiple NPY-related peptides in a stepwise diagnostic approach did not improve diagnostic performance in a way that would benefit patients. There was a limited signal suggesting NPY might add value for patients with PSA in the 4–9 ng/ml gray zone, but this finding lacked statistical strength.","whyItMatters":"PSA testing for prostate cancer is far from perfect — it produces many false positives and can miss significant cancers. There has been strong interest in finding better biomarkers, and earlier studies using less precise methods suggested NPY might be a candidate. This rigorous study using gold-standard mass spectrometry shows that NPY does not improve on PSA, which is important for redirecting research efforts toward more promising biomarker candidates.","specificNumbers":"","methodology":"The study analyzed blood plasma and tissue samples from 181 patients using liquid chromatography tandem mass spectrometry (LC-MS/MS), which is more specific than the immunoassays used in earlier NPY research. The researchers measured concentrations of NPY, its precursors, and metabolites, then compared the diagnostic accuracy of these peptides against standard PSA testing, both individually and in combination with other clinical variables like prostate volume and age.","limitations":"The sample size of 181 patients, while reasonable, may not have been large enough to detect subtle diagnostic benefits of NPY in specific subgroups. The study acknowledges that the potential benefit in the PSA gray zone (4–9 ng/ml) was limited in statistical power. Earlier positive results used immunoassays, and the discrepancy with LC-MS/MS findings raises questions about which method better captures clinically relevant NPY forms."},{"rthcId":"RPEP-08835","title":"Quantification of endogenous Angiotensin 1-10, 1-9, 1-8, 1-7, and 1-5 in human plasma using micro-UHPLC-MS/MS: Outlining the importance of the pre-analytics for reliable results.","authors":"Maurer, Jonathan; de Groot, Anke; Martin, Léon; Grouzmann, Eric; Wuerzner, Grégoire; Eugster, Philippe J","year":2024,"journal":"Journal of pharmaceutical and biomedical analysis, 243, 116101","doi":"10.1016/j.jpba.2024.116101","pmid":"38489957","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08836","title":"Quality by design (QbD) approach-based development of optimized nanocarrier to achieve quality target product profile (QTPP)-targeted lymphatic delivery.","authors":"Maurya, Rahul; Ramteke, Suman; Jain, Narendra Kumar","year":2024,"journal":"Nanotechnology, 35(26)","doi":"10.1088/1361-6528/ad355b","pmid":"38502955","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08837","title":"New fraternine analogues: Evaluation of the antiparkinsonian effect in the model of Parkinson's disease.","authors":"Mayer, Andréia Biolchi; Amaral, Henrique de Oliveira; de Oliveira, Danilo Gustavo R; Campos, Gabriel Avohay Alves; Ribeiro, Priscilla Galante; Fernandes, Solange Cristina Rego; de Souza, Adolfo Carlos Barros; de Castro, Raffael Júnio Araújo; Bocca, Anamélia Lorenzetti; Mortari, Márcia Renata","year":2024,"journal":"Neuropeptides, 103, 102390","doi":"10.1016/j.npep.2023.102390","pmid":"37984248","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08838","title":"Semaglutide use in people with obesity and type 2 diabetes from real-world utilization data: An analysis of the All of US Program.","authors":"Mayer, Craig S; Fontelo, Paul","year":2024,"journal":"Diabetes, obesity & metabolism, 26(11), 4989-4995","doi":"10.1111/dom.15911","pmid":"39248157","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08839","title":"Loading bioactive peptides within different nanocarriers to enhance their functionality and bioavailability; in vitro and in vivo studies.","authors":"Mazloomi, Narges; Safari, Barbod; Can Karaca, Asli; Karimzadeh, Laleh; Moghadasi, Shokufeh; Ghanbari, Masoud; Assadpour, Elham; Sarabandi, Khashayar; Jafari, Seid Mahdi","year":2024,"journal":"Advances in colloid and interface science, 334, 103318","doi":"10.1016/j.cis.2024.103318","pmid":"39433020","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review covers three main categories of nanocarriers for bioactive peptide delivery:\n\n1. **Lipid-based nanocarriers** (liposomes, solid lipid nanoparticles, nanoemulsions) — protect peptides from gastric degradation and enhance absorption through intestinal membranes.\n2. **Carbohydrate-based nanocarriers** (chitosan, alginate, starch nanoparticles) — provide pH-responsive release and mucoadhesive properties for targeted gut delivery.\n3. **Protein-based nanocarriers** (casein, whey, zein) — offer food-grade compatibility and controlled release.\n\nAcross all types, nanoencapsulation improved peptide stability, solubility, resistance to gastric digestion, and bioavailability while reducing or masking undesirable flavors — the key barriers to incorporating bioactive peptides into functional foods and dietary supplements.","whyItMatters":"The global market for bioactive peptides in supplements and functional foods is growing rapidly, but poor bioavailability remains the biggest technical challenge. Nanocarrier technology could unlock the full potential of food-derived peptides with proven health benefits, making them viable ingredients in everyday products rather than just promising lab findings.","specificNumbers":"","methodology":"This is a comprehensive review article synthesizing recent in vitro and in vivo studies on nanocarrier-based delivery systems for bioactive peptides. It covers formulation approaches, characterization methods, biological activity assessments, and food application studies across lipid, carbohydrate, and protein-based nanocarrier platforms.","limitations":"As a review, no new experimental data are presented. Many nanocarrier systems described have only been tested in vitro or in simple animal models — translation to commercial food products involves additional challenges like shelf stability, regulatory approval, consumer acceptance of 'nano' ingredients, and manufacturing scale-up costs. Long-term safety data for many nanocarrier materials in food applications are limited."},{"rthcId":"RPEP-08840","title":"Novel H-2Db-restricted CD8 epitope derived from mouse MAGE-type antigen P1A mediates antitumor immunity in C57BL/6 mice.","authors":"McAuliffe, James; Panetti, Silvia; Steffke, Emily; Wicki, Amanda; Pereira-Almeida, Vinnycius; Noblecourt, Laurine; Hu, Yushu; Guo, Shi Yu William; Lesenfants, Julie; Ramirez-Valdez, Ramiro Andrei; Chandrasekar, Vineethkrishna; Ahmad, Maryam; Stroobant, Vincent; Vigneron, Nathalie; Van den Eynde, Benoit J; Leung, Carol Sze Ki","year":2024,"journal":"Journal for immunotherapy of cancer, 12(10)","doi":"10.1136/jitc-2024-008998","pmid":"39384196","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08841","title":"Greater lactate accumulation does not alter peripheral concentrations of key appetite-regulating neuropeptides.","authors":"McCarthy, Seth F; Bornath, Derek P D; Tucker, Jessica A L; Cohen, Tamara R; Medeiros, Philip J; Hazell, Tom J","year":2024,"journal":"Journal of applied physiology (Bethesda, Md. : 1985), 137(5), 1397-1408","doi":"10.1152/japplphysiol.00559.2024","pmid":"39359185","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08842","title":"Physiologically relevant lactate accumulation from exercise or peripheral injection does not alter central or peripheral appetite signaling in mice.","authors":"McCarthy, Seth F; Finch, Michael S; MacPherson, Rebecca E K; Hazell, Tom J","year":2024,"journal":"Neuropeptides, 108, 102473","doi":"10.1016/j.npep.2024.102473","pmid":"39332138","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08843","title":"Dioxythiophene/Nafion Polymer Composite Membranes for Tunable Size-Based Selectivity in the Voltammetric Detection of Small Neuropeptides.","authors":"McCarty, Gregory S; Meunier, Carl J; Sombers, Leslie A","year":2024,"journal":"ACS sensors, 9(10), 5109-5115","doi":"10.1021/acssensors.4c00848","pmid":"39319559","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08844","title":"Comparative effectiveness of sodium-glucose cotransporter-2 inhibitors for recurrent nephrolithiasis among patients with pre-existing nephrolithiasis or gout: target trial emulation studies.","authors":"McCormick, Natalie; Yokose, Chio; Lu, Na; Wexler, Deborah J; Aviña-Zubieta, J Antonio; De Vera, Mary A; Chigurupati, Saiajay; Tan, Kiara; Chen, Chixiang; McCoy, Rozalina; Curhan, Gary C; Choi, Hyon K","year":2024,"journal":"BMJ (Clinical research ed.), 387, e080035","doi":"10.1136/bmj-2024-080035","pmid":"39477370","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08845","title":"Safety, tolerability, and efficacy of NLY01 in early untreated Parkinson's disease: a randomised, double-blind, placebo-controlled trial.","authors":"McGarry, Andrew; Rosanbalm, Shane; Leinonen, Mika; Olanow, C Warren; To, Dennis; Bell, Adam; Lee, Daniel; Chang, Jamie; Dubow, Jordan; Dhall, Rohit; Burdick, Daniel; Parashos, Sotirios; Feuerstein, Jeanne; Quinn, Joseph; Pahwa, Rajesh; Afshari, Mitra; Ramirez-Zamora, Aldolfo; Chou, Kelvin; Tarakad, Arjun; Luca, Corneliu; Klos, Kevin; Bordelon, Yvette; St Hiliare, Marie-Helene; Shprecher, David; Lee, Seulki; Dawson, Ted M; Roschke, Viktor; Kieburtz, Karl","year":2024,"journal":"The Lancet. Neurology, 23(1), 37-45","doi":"10.1016/S1474-4422(23)00378-2","pmid":"38101901","tags":[],"studyType":"randomized-controlled-trial","evidenceStrength":"high","keyFinding":"NLY01 — a brain-penetrant, pegylated, longer-lasting version of the GLP-1 agonist exenatide — showed NO benefit for Parkinson's disease in this rigorous 36-week trial. Neither the 2.5 mg nor 5.0 mg dose improved motor or non-motor symptoms compared to placebo on the MDS-UPDRS scale (p=0.77 and p=0.79, respectively).\n\nThe drug was designed to reduce brain inflammation by suppressing microglial activation, a mechanism distinct from its metabolic effects. Despite strong preclinical rationale and adequate dosing, NLY01 simply did not work for Parkinson's disease symptoms. An exploratory subgroup analysis hinted at possible motor benefit in younger patients, but this requires replication before drawing conclusions. Side effects were predominantly gastrointestinal: nausea affected 39-58% of treated patients versus 19% on placebo.","whyItMatters":"There has been enormous excitement about GLP-1 agonists potentially treating neurodegenerative diseases like Parkinson's and Alzheimer's. This Lancet Neurology trial delivers a sobering reality check: a purpose-built, brain-penetrant GLP-1 agonist failed to improve Parkinson's symptoms in a well-designed trial. This doesn't rule out all GLP-1 approaches for neurodegeneration, but it significantly tempers expectations and highlights how difficult it is to translate promising preclinical neuroscience into clinical benefit.","specificNumbers":"n=255 randomized (85 per group) · 36-week duration · 58 sites across USA · 2.5 mg vs 5.0 mg vs placebo · Primary endpoint: p=0.77 and p=0.79 (no benefit) · Nausea: 39-58% active vs 19% placebo · No deaths · 447 screened","methodology":"This was a 36-week, randomized, double-blind, placebo-controlled trial conducted at 58 movement disorder clinics across the United States. 255 participants with early, untreated Parkinson's disease were randomized 1:1:1 to NLY01 2.5 mg, NLY01 5.0 mg, or placebo. The primary endpoint was change in the MDS-UPDRS parts II and III (measuring motor and daily living function). All participants, investigators, and staff were blinded. Safety was monitored comprehensively including adverse events, ECGs, labs, and scales for suicidality, sleepiness, impulsivity, and depression.","limitations":"The 36-week duration may have been insufficient to detect neuroprotective effects that emerge more slowly. The study enrolled early, untreated patients who may deteriorate slowly, making it harder to show treatment differences. The subgroup finding in younger patients is hypothesis-generating only and could be a chance finding. Parkinson's disease is heterogeneous, and microglia-mediated inflammation may only drive pathology in certain patient subgroups."},{"rthcId":"RPEP-08846","title":"Efficacy and safety of once-weekly semaglutide 2·4 mg versus placebo in people with obesity and prediabetes (STEP 10): a randomised, double-blind, placebo-controlled, multicentre phase 3 trial.","authors":"McGowan, Barbara M; Bruun, Jens M; Capehorn, Matt; Pedersen, Sue D; Pietiläinen, Kirsi H; Muniraju, Hanna Angelene Kudiyanur; Quiroga, Maria; Varbo, Anette; Lau, David C W","year":2024,"journal":"The lancet. Diabetes & endocrinology, 12(9), 631-642","doi":"10.1016/S2213-8587(24)00182-7","pmid":"39089293","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08847","title":"Increased reporting of accidental overdose with glucagon-like peptide-1 receptor agonists: a population-based study.","authors":"McIntyre, Roger S; Kwan, Angela T H","year":2024,"journal":"Expert opinion on drug safety, 1-6","doi":"10.1080/14740338.2024.2430306","pmid":"39552465","tags":[],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"Accidental overdoses with GLP-1 receptor agonists are being reported at disproportionately high rates to the FDA. Across 3,348 reports from 2003 to early 2024, every GLP-1 drug in the class showed significantly elevated reporting odds ratios for accidental overdose:\n\n- ROR range: 2.64 to 61.12 (all statistically significant, p < 0.008)\n- Affected drugs: semaglutide, dulaglutide, exenatide, liraglutide, and tirzepatide\n\nThe authors link this to patients accessing GLP-1 drugs through online and compounding pharmacies due to cost and availability barriers, with the greatest risk falling on racial, ethnic, and socioeconomically disadvantaged populations.","whyItMatters":"GLP-1 drugs have become the most sought-after medications in the world, but shortages and costs exceeding $1,000/month are pushing patients toward online pharmacies and compounding services where dosing errors are more likely. This study quantifies the consequence: a significant spike in accidental overdoses across the entire GLP-1 class. The equity dimension is critical — the people most likely to be harmed are those with the least access to FDA-approved products and proper medical supervision.","specificNumbers":"3,348 accidental overdose reports · ROR range 2.64–61.12 · all p < 0.008 · 5 GLP-1 drugs affected · Q4 2003 to Q1 2024 · compared to niacin baseline","methodology":"Retrospective pharmacovigilance analysis using the FDA Adverse Event Reporting System (FAERS). Researchers retrieved all accidental overdose case reports for GLP-1 RAs from Q4 2003 to Q1 2024 using OpenVigil 2.1. Disproportionality was assessed using reporting odds ratios (ROR) with 95% confidence intervals, with niacin as the comparator.","limitations":"FAERS is a voluntary reporting system — overdoses may be underreported or overreported depending on public awareness and media coverage. The study cannot prove that online/compounding pharmacy access caused the overdoses — only that the association exists. Selection of niacin as comparator may influence ROR magnitude. Individual case details (severity, outcomes, source of medication) were not analyzed. Reporting bias may have increased as GLP-1 drugs gained media attention."},{"rthcId":"RPEP-08848","title":"Psychotropic Drug-Related Weight Gain and Its Treatment.","authors":"McIntyre, Roger S; Kwan, Angela T H; Rosenblat, Joshua D; Teopiz, Kayla M; Mansur, Rodrigo B","year":2024,"journal":"The American journal of psychiatry, 181(1), 26-38","doi":"10.1176/appi.ajp.20230922","pmid":"38161305","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Psychotropic drug-related weight gain (PDWG) is a major barrier to psychiatric treatment adherence. The review found:\n\n- Differential weight gain liability exists across antipsychotics, antidepressants, and anticonvulsants, and newer agents with lower liability should be prioritized\n- Lithium's weight gain effect is lower than previously thought\n- Lifestyle modification is effective and comparable to general population results\n- Metformin is the most-studied pharmacological treatment for both prevention and treatment of PDWG\n- GLP-1 receptor agonists (liraglutide, exenatide, semaglutide) show promising emerging data\n- Most other pharmacologic antidotes (topiramate, H2 antagonists) have only low-confidence evidence\n- Future research priorities include large trials of GLP-1 RAs and tirzepatide in psychiatric populations","whyItMatters":"Psychiatric patients already face elevated obesity risk, and weight gain from medications compounds the problem while driving treatment non-adherence. GLP-1 receptor agonists could address a critical unmet need by allowing patients to maintain psychiatric treatment without the metabolic costs that currently force many to choose between mental health and physical health.","specificNumbers":"","methodology":"This is a narrative review published in The American Journal of Psychiatry, synthesizing evidence on the epidemiology, risk factors, prevention, and treatment of psychotropic drug-related weight gain across antipsychotics, antidepressants, anticonvulsants, and lithium.","limitations":"This is a narrative review, not a systematic review with meta-analysis. The GLP-1 RA evidence for PDWG specifically is still early-stage, with most data coming from small studies. The review does not provide pooled effect sizes. Interactions between GLP-1 RAs and psychiatric medications have not been well studied."},{"rthcId":"RPEP-08849","title":"The association between glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and suicidality: reports to the Food and Drug Administration Adverse Event Reporting System (FAERS).","authors":"McIntyre, Roger S; Mansur, Rodrigo B; Rosenblat, Joshua D; Kwan, Angela T H","year":2024,"journal":"Expert opinion on drug safety, 23(1), 47-55","doi":"10.1080/14740338.2023.2295397","pmid":"38087976","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide and liraglutide showed disproportionate reporting of suicidal ideation and 'depression/suicidal' events in the FDA Adverse Event Reporting System, with reporting odds ratios whose lower 95% confidence interval exceeded 1.0 (indicating statistical significance).\n\nCritically, no disproportionate reporting of more severe outcomes — suicidal behavior, suicide attempts, or completed suicide — was observed for any FDA-approved GLP-1 receptor agonist. When the data was evaluated using Bradford Hill criteria for causality and confounding factors were considered, the researchers found no causal link between GLP-1 RAs and suicidality.","whyItMatters":"With tens of millions of people taking semaglutide and liraglutide, even a small increase in suicide risk would be a major public health concern. This analysis of the largest pharmacovigilance database in the world provides reassurance: while suicidal thoughts are reported more frequently with these drugs, the more serious outcomes (attempts and completions) are not elevated, and no causal link was found. This is critical context for the ongoing FDA investigation and for prescribers weighing risks and benefits.","specificNumbers":"","methodology":"Pharmacovigilance analysis using the FDA Adverse Event Reporting System (FAERS) database. Reports from 2005 through October 2023 were analyzed for suicidal ideation, depression/suicidal events, suicidal behavior, suicide attempts, and completed suicide associated with all FDA-approved GLP-1 receptor agonists. Data was compared against other glucose-lowering agents using reporting odds ratios (ROR), with significance defined as the lower 95% CI exceeding 1.0. Bradford Hill criteria were applied to evaluate potential causality.","limitations":"FAERS is a voluntary reporting system subject to reporting bias, underreporting, and the inability to establish causation. The disproportionate reporting for semaglutide and liraglutide could reflect media attention and the Weber effect (increased reporting for newer, high-profile drugs). The analysis cannot control for all confounders — obesity and diabetes independently increase depression and suicidality risk. Reporting odds ratios measure disproportionality in reporting, not actual risk. The study period predates the massive expansion of GLP-1 use for weight loss in otherwise healthy populations."},{"rthcId":"RPEP-08850","title":"Calorie restriction activates a gastric Notch-FOXO1 pathway to expand ghrelin cells.","authors":"McKimpson, Wendy M; Spiegel, Sophia; Mukhanova, Maria; Kraakman, Michael; Du, Wen; Kitamoto, Takumi; Yu, Junjie; Deng, Zhaobin; Pajvani, Utpal; Accili, Domenico","year":2024,"journal":"The Journal of cell biology, 223(10)","doi":"10.1083/jcb.202305093","pmid":"38958606","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Calorie restriction increased chromogranin A-positive endocrine cells, including ghrelin-producing cells, in mouse stomachs. This expansion was driven by Notch-dependent signaling that activates FOXO1, which promotes a specific subpopulation of endocrine progenitor cells (FOXO1/Neurog3+) to proliferate and differentiate. Blocking Notch with gamma-secretase inhibitors reversed the effect. Uniquely, calorie restriction decreased Lgr5+ stem cells in the stomach (opposite to its effect in the intestine) while increasing endocrine progenitors. FOXO1 activation alone was sufficient to promote endocrine cell differentiation even without Notch signaling. Tirzepatide also expanded ghrelin-producing cells in mice.","whyItMatters":"This study reveals how calorie restriction — one of the most robust lifespan-extending interventions — reshapes the stomach's hormone-producing machinery at the molecular level. Understanding the Notch-FOXO1 pathway could open doors to drugs that mimic the gut benefits of calorie restriction without actual food restriction. The finding that tirzepatide expands ghrelin cells adds a new dimension to understanding how GLP-1-based metabolic drugs affect the gastrointestinal tract.","specificNumbers":"","methodology":"Researchers used calorie-restricted mice and examined stomach tissue for endocrine cell changes. They employed primary cell cultures, genetically modified reporter mice (for tracking Lgr5+ stem cells and Neurog3+ progenitors), and pharmacological tools including the Notch inhibitors DAPT and PF-03084014 and the ghrelin receptor antagonist GHRP-6. They also tested tirzepatide administration. Techniques included immunostaining, gene expression analysis, and cell proliferation assays.","limitations":"This was entirely a mouse study, and the findings may not translate directly to humans. The abstract does not specify sample sizes for the various experimental groups. The tirzepatide finding is mentioned briefly without detailed dose-response data. The study focused on cell numbers and signaling pathways but did not measure functional outcomes like circulating ghrelin levels or metabolic effects of the expanded ghrelin cell population."},{"rthcId":"RPEP-08851","title":"Regulator of G-protein signaling expression in human intestinal enteroendocrine cells and potential role in satiety hormone secretion in health and obesity.","authors":"McRae, Alison N; Ticho, Alexander L; Liu, Yuanhang; Ricardo-Silgado, Maria Laura; Mangena, Nothando N; Jassir, Fauzi Feris; Gonzalez-Izundegui, Daniel; Calderon, Gerardo; Rohakhtar, Fariborz Rakhshan; Simon, Vernadette; Li, Ying; Leggett, Cadman; Hurtado, Daniela; LaRusso, Nicholas; Acosta, Andres J","year":2024,"journal":"EBioMedicine, 107, 105283","doi":"10.1016/j.ebiom.2024.105283","pmid":"39142076","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08852","title":"Patient perspectives on incretin-based weight loss medications and relationship with demographic factors.","authors":"McVay, Megan A; Moore, Wendy S; Wilkins, Francesca L; Jackson, Jalen R; Robinson, Michael D","year":2024,"journal":"Obesity science & practice, 10(4), e783","doi":"10.1002/osp4.783","pmid":"39109182","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08853","title":"Unlocking the Potential: Semaglutide's Impact on Alzheimer's and Parkinson's Disease in Animal Models.","authors":"Meca, Andreea Daniela; Boboc, Ianis Kevyn Stefan; Mititelu-Tartau, Liliana; Bogdan, Maria","year":2024,"journal":"Current issues in molecular biology, 46(6), 5929-5949","doi":"10.3390/cimb46060354","pmid":"38921025","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08854","title":"Updated Canadian Headache Society Migraine Prevention Guideline with Systematic Review and Meta-analysis.","authors":"Medrea, Ioana; Cooper, Paul; Langman, Marissa; Sandoe, Claire H; Amoozegar, Farnaz; Hussain, Wasif M; Bradi, Ana C; Dawe, Jessica; Guay, Meagan; Perreault, Francois; Reid, Stuart; Todd, Candice; Skidmore, Becky; Christie, Suzanne N","year":2024,"journal":"The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques, 1-23","doi":"10.1017/cjn.2024.285","pmid":"39506371","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08855","title":"Lipid-Based Nanoparticles as Oral Drug Delivery Systems: Overcoming Poor Gastrointestinal Absorption and Enhancing Bioavailability of Peptide and Protein Therapeutics.","authors":"Mehrdadi, Soheil","year":2024,"journal":"Advanced pharmaceutical bulletin, 14(1), 48-66","doi":"10.34172/apb.2024.016","pmid":"38585451","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08856","title":"Recent Progress in the Oral Delivery of Therapeutic Peptides and Proteins: Overview of Pharmaceutical Strategies to Overcome Absorption Hurdles.","authors":"Mehrotra, Sonal; Kalyan Bg, Pavan; Nayak, Pawan Ganesh; Joseph, Alex; Manikkath, Jyothsna","year":2024,"journal":"Advanced pharmaceutical bulletin, 14(1), 11-33","doi":"10.34172/apb.2024.009","pmid":"38585454","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08857","title":"Concomitant use of calcitonin gene-related peptide (CGRP) antagonists with azole antifungals in patients with hematological malignancies.","authors":"Mehta, Purav; Ngo, Dat; Tinajero, Jose","year":2024,"journal":"Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners, 30(7), 1255-1258","doi":"10.1177/10781552241265884","pmid":"39052976","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08858","title":"Dulaglutide restores endothelial progenitor cell levels in diabetic mice and mitigates high glucose-induced endothelial injury through SIRT1-mediated mitochondrial fission.","authors":"Mei, Xi; Li, Yao; Wu, Jinlin; Liao, Lumiu; Lu, Di; Qiu, Ping; Yang, Hui-Lan; Tang, Ming-Wei; Liang, Xin-Ying; Liu, Dongfang","year":2024,"journal":"Biochemical and biophysical research communications, 716, 150002","doi":"10.1016/j.bbrc.2024.150002","pmid":"38697011","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08859","title":"Novel insight into atogepant mechanisms of action in migraine prevention.","authors":"Melo-Carrillo, Agustin; Strassman, Andrew M; Broide, Ron; Adams, Aubrey; Dabruzzo, Brett; Brin, Mitchell; Burstein, Rami","year":2024,"journal":"Brain : a journal of neurology, 147(8), 2884-2896","doi":"10.1093/brain/awae062","pmid":"38411458","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08860","title":"SEMAGLUTIDE: Weight loss, glycaemic control and safety profile in obese patients with and without type-II diabetes-An experience from Karachi, Pakistan.","authors":"Memon, Muhammad Y; Ahsan, Tasnim; Jabeen, Rukhshanda; Latif, Saba; Qasim, Saeeda F; Imran, Paras","year":2024,"journal":"Journal of family medicine and primary care, 13(10), 4188-4193","doi":"10.4103/jfmpc.jfmpc_159_24","pmid":"39629429","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Average weight loss was 5.81 ± 2.64 kg at 3 months and 9.86 ± 3.54 kg at 6 months. Weight loss was similar in patients with and without type 2 diabetes. Significant reductions were observed in HbA1c, BMI, and cholesterol levels (all p<0.001). By 6 months, 40% of patients remained on 0.5 mg, 33.8% escalated to 1 mg, and 24.6% reached 2 mg weekly. Adverse effects were reported by 55.4% at 3 months but declined to 34.5% at 6 months, with most being mild-to-moderate GI symptoms. Only 1.5% reduced their dose due to side effects.","whyItMatters":"Most GLP-1 agonist data comes from Western populations. This study provides real-world evidence from South Asia, where obesity and diabetes patterns differ and where access to these medications is rapidly expanding. The finding that even low-dose semaglutide (most patients on 0.5 mg) produces meaningful weight loss in this population has practical implications for prescribing in resource-limited settings where higher doses may be cost-prohibitive.","specificNumbers":"","methodology":"Observational analytic cohort study at a private medical institute in Karachi, Pakistan, from August 2022 to January 2023. Enrolled 65 obese adults (>18 years) with or without type 2 diabetes. Semaglutide was started at 0.25 mg and escalated every 4 weeks to the maximally tolerated dose (up to 2 mg/week). Patients were evaluated at baseline, 3 months, and 6 months for weight, BMI, HbA1c, lipid profiles, and adverse effects.","limitations":"Small sample size (65 patients) at a single private clinic limits generalizability. No control group means results could be influenced by concurrent lifestyle changes. Observational design cannot establish causation. Six-month follow-up is relatively short. The study was conducted at a private institute, which may not represent the broader Pakistani population in terms of socioeconomic status, adherence, and access to care. The abstract contains apparent formatting errors in the p-value reporting."},{"rthcId":"RPEP-08861","title":"Charge-switchable cell-penetrating peptides for rerouting nanoparticles to glioblastoma treatment.","authors":"Mendes, Maria; Nunes, Sandra; Cova, Tânia; Branco, Francisco; Dyrks, Michael; Koksch, Beate; Vale, Nuno; Sousa, João; Pais, Alberto; Vitorino, Carla","year":2024,"journal":"Colloids and surfaces. B, Biointerfaces, 241, 113983","doi":"10.1016/j.colsurfb.2024.113983","pmid":"38850741","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08862","title":"The functional role of m6A demethylase ALKBH5 in cardiomyocyte hypertrophy.","authors":"Meng, Chen; Su, Haibi; Shu, Meiling; Shen, Feng; Lu, Yijie; Wu, Shishi; Su, Zhenghua; Yu, Mengyao; Yang, Di","year":2024,"journal":"Cell death & disease, 15(9), 683","doi":"10.1038/s41419-024-07053-2","pmid":"39294131","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08863","title":"Optimization of Extraction Process and Activity of Angiotensin-Converting Enzyme (ACE) Inhibitory Peptide from Walnut Meal.","authors":"Meng, Meng; She, Ziyi; Feng, Yinyin; Zhang, Junhan; Han, Ran; Qi, Yanlong; Sun, Lina; Sun, Huiqing","year":2024,"journal":"Foods (Basel, Switzerland), 13(7)","doi":"10.3390/foods13071067","pmid":"38611371","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08864","title":"Expression and Clinical Implications of pro-BNP and Soluble ST2 in Chronic Heart Failure.","authors":"Meng, Xing; Zhang, Kai; Zeng, Wan-Jie; Hu, Zhen-Hua","year":2024,"journal":"British journal of hospital medicine (London, England : 2005), 85(12), 1-13","doi":"10.12968/hmed.2024.0465","pmid":"39831497","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08865","title":"Weichang' an pill alleviates functional dyspepsia through modulating brain-gut peptides and gut microbiota.","authors":"Mengting, Liao; Tao, L I; Fuhao, Chu; Yan, Chen; Ni, Lou; Yuan, Zhuang; Rongqiang, B O; Xia, Ding","year":2024,"journal":"Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan, 44(6), 1177-1186","doi":"10.19852/j.cnki.jtcm.2024.06.006","pmid":"39617703","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08866","title":"A systematic review on the efficacy of GLP-1 receptor agonists in mitigating psychotropic drug-related weight gain.","authors":"Menon, Trisha; Lee, Serene; Gong, Xuan Yi; Wong, Sabrina; Le, Gia Han; Kwan, Angela T H; Teopiz, Kayla M; Ho, Roger; Cao, Bing; Rhee, Taeho Greg; Jing Zheng, Yang; Valentino, Kyle; Lin, Kangguang; Vinberg, Maj; Lo, Heidi K Y; McIntyre, Roger S","year":2024,"journal":"CNS spectrums, 1-7","doi":"10.1017/S1092852924000531","pmid":"39582175","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08867","title":"Tirzepatide for Lipodystrophy.","authors":"Meral, Rasimcan; Celik Guler, Merve; Kaba, Diarratou; Prativadi, Jeevitha; Frontera, Eric D; Foss-Freitas, Maria Cristina; Nachawi, Noura; Broome, David T; Lightbourne, Marissa; Brown, Rebecca J; Taylor, Simeon I; Oral, Elif A","year":2024,"journal":"medRxiv : the preprint server for health sciences","doi":"10.1101/2024.09.25.24313345","pmid":"39802778","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08868","title":"De novo development of small cyclic peptides that are orally bioavailable.","authors":"Merz, Manuel L; Habeshian, Sevan; Li, Bo; David, Jean-Alexandre G L; Nielsen, Alexander L; Ji, Xinjian; Il Khwildy, Khaled; Duany Benitez, Maury M; Phothirath, Phoukham; Heinis, Christian","year":2024,"journal":"Nature chemical biology, 20(5), 624-633","doi":"10.1038/s41589-023-01496-y","pmid":"38155304","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08869","title":"Differential effects of liraglutide naltrexone/bupropion, and caloric restriction on metabolic parameters and beta-cell regeneration in type 2 diabetic rat model: role of beta arrestin 1.","authors":"Merzeban, Dina H; El Amin Ali, Amani M; Hammad, Reem O; Elmahdi, Mohamed H; Sofi, Marwa A; Mahmoud, Rania H; Metwally, Sayed M; El Ebiary, Ahmed M","year":2024,"journal":"Journal of molecular histology, 56(1), 50","doi":"10.1007/s10735-024-10326-x","pmid":"39704859","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 50 male diabetic rats across five groups, all three interventions significantly improved body weight, BMI, blood glucose, insulin, lipid profiles, and atherogenic indices compared to untreated diabetic controls.\n\nKey differentiators:\n- **Beta-cell regeneration**: Liraglutide and caloric restriction significantly increased anti-insulin antibodies and Ki67 (a cell proliferation marker) in the pancreas, indicating beta-cell regeneration. Naltrexone/bupropion (NTX+BUP) showed no significant regenerative effect.\n- **Beta-arrestin-1**: Liraglutide significantly decreased beta-arrestin-1 levels compared to both NTX+BUP and caloric restriction — a unique molecular signature.\n- **Weight loss**: NTX+BUP and caloric restriction produced greater weight loss than liraglutide, yet liraglutide was superior for beta-cell outcomes.","whyItMatters":"Most diabetes treatments manage symptoms but don't fix the underlying problem — progressive beta-cell loss. This study shows liraglutide can actually regenerate beta cells, potentially reversing the disease process rather than just controlling it. The finding that weight loss alone (from NTX+BUP) doesn't regenerate beta cells while liraglutide does suggests the GLP-1 pathway has specific regenerative properties beyond its metabolic effects.","specificNumbers":"","methodology":"Fifty male albino rats were randomized into five groups: normal control, diabetic control, diabetic + 50% caloric restriction, diabetic + NTX+BUP (4 mg/45 mg/kg/day oral), and diabetic + liraglutide (0.3 mg/kg/day subcutaneous). Outcomes included body weight, BMI, serum glucose, insulin, lipid profile, atherogenic indices, beta-arrestin-1 levels, pancreatic histopathology, and immunohistochemical staining for insulin and Ki67 (proliferation marker).","limitations":"This is a preclinical rat study, and beta-cell regeneration dynamics may differ significantly in humans. The sample size (10 per group) is modest. The study used a chemically induced diabetes model, which may not perfectly replicate the gradual onset of human type 2 diabetes. Only male rats were studied. The duration of treatment and long-term sustainability of beta-cell regeneration were not assessed."},{"rthcId":"RPEP-08870","title":"A human obesity-associated MC4R mutation with defective Gq/11α signaling leads to hyperphagia in mice.","authors":"Metzger, Peter J; Zhang, Aileen; Carlson, Bradley A; Sun, Hui; Cui, Zhenzhong; Li, Yongqi; Jahnke, Marshal T; Layton, Daniel R; Gupta, Meenakshi B; Liu, Naili; Kostenis, Evi; Gavrilova, Oksana; Chen, Min; Weinstein, Lee S","year":2024,"journal":"The Journal of clinical investigation, 134(4)","doi":"10.1172/JCI165418","pmid":"38175730","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08871","title":"Effects and mechanisms of long-acting glucagon-like peptide-1 receptor agonist semaglutide on microglia phenotypic transformation and neuroinflammation after cerebral ischemia/reperfusion in rats.","authors":"Mi, Rulin; Cheng, Huifeng; Chen, Rui; Bai, Bo; Li, An; Gao, Fankai; Xue, Guofang","year":2024,"journal":"Brain circulation, 10(4), 354-365","doi":"10.4103/bc.bc_38_24","pmid":"40012598","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In a rat transient middle cerebral artery occlusion (tMCAO) stroke model, semaglutide treatment produced multiple neuroprotective effects:\n\n- Decreased neurological deficit scores on days 1, 3, and 7 post-intervention\n- Reduced cerebral infarct volume (measured by TTC staining)\n- Decreased CD68 expression (marker of pro-inflammatory M1 microglial activation)\n- Decreased TNF-α levels (pro-inflammatory cytokine)\n- Increased CD206 expression (marker of anti-inflammatory M2 microglial activation)\n- Increased TGF-β levels (anti-inflammatory mediator)\n- Reduced P65 levels in the NF-κB signaling cascade\n\nThe mechanism involves semaglutide promoting microglial phenotype transformation from M1 (neurotoxic) to M2 (neuroprotective) while inhibiting NF-κB-driven inflammation.","whyItMatters":"Stroke is the second leading cause of death worldwide, and reperfusion injury worsens outcomes even after successful blood flow restoration. There are currently no approved drugs to specifically prevent this secondary damage. If semaglutide — a drug already prescribed to millions — can protect the brain during stroke recovery, it could be rapidly repurposed for this new indication. The finding also adds to growing evidence that GLP-1 drugs have neuroprotective properties beyond their metabolic effects.","specificNumbers":"","methodology":"A transient middle cerebral artery occlusion (tMCAO) rat model was established to simulate ischemic stroke with reperfusion. Semaglutide was administered as treatment. Neurological deficits were assessed using modified neurological severity scores on days 1, 3, and 7. Infarct volume was quantified by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Microglial phenotypes and inflammatory markers were assessed using immunohistochemistry and immunoblotting (Western blot) for CD68 (M1), CD206 (M2), TNF-α, TGF-β, and NF-κB p65.","limitations":"This is a rat model of stroke that may not fully replicate human cerebrovascular disease. The tMCAO model produces a standardized ischemic injury, but human strokes vary enormously in location, size, and timing. The semaglutide dose and dosing schedule are not detailed in the abstract. Sample sizes per group are not specified. The 7-day observation period is short for assessing long-term neurological recovery. The M1/M2 microglial polarization framework is an oversimplification of complex microglial biology. No behavioral or cognitive assessments beyond basic neurological scoring are described."},{"rthcId":"RPEP-08872","title":"Cathelicidin peptide LL-37: A multifunctional peptide involved in heart disease.","authors":"Miao, Shuo; Liu, Houde; Yang, Qingyu; Zhang, Yaping; Chen, Tao; Chen, Shuai; Mao, Xin; Zhang, Qingsong","year":2024,"journal":"Pharmacological research, 210, 107529","doi":"10.1016/j.phrs.2024.107529","pmid":"39615616","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"LL-37, the only human cathelicidin antimicrobial peptide, has been found to regulate multiple cardiovascular processes beyond its traditional antimicrobial role:\n\n- Atherosclerosis regulation — LL-37 influences plaque formation and stability in blood vessels\n- Thrombosis modulation — the peptide affects blood clot formation\n- Inflammatory response control — LL-37 modulates cardiac inflammatory pathways\n- Cardiac hypertrophy regulation — the peptide influences heart muscle thickening\n\nEngineered LL-37-related peptides have been developed and shown to regulate disease progression in experimental models, demonstrating potential for clinical application in cardiovascular disease.","whyItMatters":"Heart disease remains the leading cause of death worldwide, and current treatments primarily target individual risk factors (blood pressure, cholesterol, blood sugar). Discovering that an endogenous peptide like LL-37 simultaneously influences multiple cardiovascular pathways — from plaque formation to blood clotting to heart muscle remodeling — suggests a new therapeutic paradigm. Peptide-based therapies modeled on LL-37 could potentially address multiple aspects of heart disease simultaneously.","specificNumbers":"","methodology":"This is a comprehensive review article that synthesizes published research on LL-37's roles in cardiovascular disease. The authors surveyed studies covering LL-37's involvement in atherosclerosis, thrombosis, inflammation, cardiac hypertrophy, and related pathways, as well as research on engineered LL-37-derived peptides.","limitations":"As a review article, this paper synthesizes existing evidence rather than generating new data. The cardiovascular roles of LL-37 have been demonstrated primarily in preclinical models, with limited human clinical evidence. The review does not include a systematic search methodology or meta-analysis. Whether LL-37's diverse cardiovascular effects are beneficial or harmful may depend on context, dosing, and disease stage — complexities that are not fully resolved."},{"rthcId":"RPEP-08873","title":"Sex-Differences in Response to Treatment with Liraglutide 3.0 mg.","authors":"Milani, Ilaria; Guarisco, Gloria; Chinucci, Marianna; Gaita, Chiara; Leonetti, Frida; Capoccia, Danila","year":2024,"journal":"Journal of clinical medicine, 13(12)","doi":"10.3390/jcm13123369","pmid":"38929898","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08874","title":"Factors Influencing the Development and Severity of Cognitive Decline in Patients with Chronic Heart Failure.","authors":"Militaru, Marius; Lighezan, Daniel Florin; Tudoran, Cristina; Tudoran, Mariana; Militaru, Anda Gabriela","year":2024,"journal":"Medicina (Kaunas, Lithuania), 60(11)","doi":"10.3390/medicina60111859","pmid":"39597044","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08875","title":"Effects of Oral Semaglutide on Renal Function in Diabetic Kidney Disease: A Short-term Clinical Study.","authors":"Mima, Akira; Kidooka, Sayumi; Nakamoto, Takahiro; Kido, Suguru; Gotoda, Hidemasa; Lee, Rina; Murakami, Ami; Lee, Shinji","year":2024,"journal":"In vivo (Athens, Greece), 38(1), 308-312","doi":"10.21873/invivo.13440","pmid":"38148042","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08876","title":"Integrating Drug Target Information in Deep Learning Models to Predict the Risk of Adverse Events in Patients with Comorbid Post-Traumatic Stress Disorder and Alcohol Use Disorder.","authors":"Miranda, Oshin; Qi, Xiguang; Brannock, M Daniel; Whitworth, Ryan; Kosten, Thomas R; Ryan, Neal David; Haas, Gretchen L; Kirisci, Levent; Wang, Lirong","year":2024,"journal":"Biomedicines, 12(12)","doi":"10.3390/biomedicines12122772","pmid":"39767679","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08877","title":"Application of Fabric Phase Sorptive Extraction as a Green Method for the Analysis of 10 Anti-Diabetic Drugs in Environmental Water Samples.","authors":"Misolas, Augosto; Sleiman, Mohamad; Sakkas, Vasilios","year":2024,"journal":"Molecules (Basel, Switzerland), 29(20)","doi":"10.3390/molecules29204834","pmid":"39459205","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08878","title":"Preventive drug treatments for adults with chronic migraine: a systematic review with economic modelling.","authors":"Mistry, Hema; Naghdi, Seyran; Brown, Anna; Rees, Sophie; Madan, Jason; Grove, Amy; Khanal, Saval; Duncan, Callum; Matharu, Manjit; Cooklin, Andrew; Aksentyte, Aiva; Davies, Natasha; Underwood, Martin","year":2024,"journal":"Health technology assessment (Winchester, England), 28(63), 1-329","doi":"10.3310/AYWA5297","pmid":"39365169","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08879","title":"Porcine-derived collagen peptides promote re-epithelialisation through activation of integrin signalling.","authors":"Mistry, Krishan; Richardson, Grant; Vleminckx, Sara; Smith, Robert; Gevaert, Elien; Lovat, Penny E","year":2024,"journal":"Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society, 32(4), 475-486","doi":"10.1111/wrr.13177","pmid":"38572659","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08880","title":"Translational approach to establish the cardiometabolic health effects and mechanisms of action of fish nutrients-it takes a village.","authors":"Mitchell, Patricia L; Pilon, Geneviève; Bazinet, Laurent; Gagnon, Claudia; Weisnagel, S John; Jacques, Hélène; Vohl, Marie-Claude; Marette, André","year":2024,"journal":"Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme, 49(11), 1600-1605","doi":"10.1139/apnm-2024-0111","pmid":"39137439","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08881","title":"Cyclic β2,3-amino acids improve the serum stability of macrocyclic peptide inhibitors targeting the SARS-CoV-2 main protease.","authors":"Miura, Takashi; Malla, Tika R; Brewitz, Lennart; Tumber, Anthony; Salah, Eidarus; Lee, Kang Ju; Terasaka, Naohiro; Owen, C David; Strain-Damerell, Claire; Lukacik, Petra; Walsh, Martin A; Kawamura, Akane; Schofield, Christopher J; Katoh, Takayuki; Suga, Hiroaki","year":2024,"journal":"Bulletin of the Chemical Society of Japan, 97(5), uoae018","doi":"10.1093/bulcsj/uoae018","pmid":"38828441","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08882","title":"Cell-Penetrating Peptide-Mediated Biomolecule Transportation in Artificial Lipid Vesicles and Living Cells.","authors":"Miwa, Akari; Kamiya, Koki","year":2024,"journal":"Molecules (Basel, Switzerland), 29(14)","doi":"10.3390/molecules29143339","pmid":"39064917","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08883","title":"Interactions between glucagon like peptide 1 (GLP-1) and estrogens regulates lipid metabolism.","authors":"Model, Jorge F A; Normann, Rafaella S; Vogt, Éverton L; Dentz, Maiza Von; de Amaral, Marjoriane; Xu, Rui; Bachvaroff, Tsvetan; Spritzer, Poli Mara; Chung, J Sook; Vinagre, Anapaula S","year":2024,"journal":"Biochemical pharmacology, 230(Pt 3), 116623","doi":"10.1016/j.bcp.2024.116623","pmid":"39542180","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08884","title":"Liraglutide versus pramlintide in protecting against cognitive function impairment through affecting PI3K/AKT/GSK-3β/TTBK1 pathway and decreasing Tau hyperphosphorylation in high-fat diet- streptozocin rat model.","authors":"Moghazy, Hoda M; Abdelhaliem, Nesreen G; Mohammed, Sherine Ahmed; Hassan, Asmaa; Abdelrahman, Amany","year":2024,"journal":"Pflugers Archiv : European journal of physiology, 476(5), 779-795","doi":"10.1007/s00424-024-02933-0","pmid":"38536493","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08885","title":"Direct Comparison of Treatment Outcome Between the Botulinum Toxin and Calcitonin Gene-Related Peptide Monoclonal Antibody in Migraine Patients.","authors":"Mohammad Alabdali, Majed; Rafique, Nazish; AlDossary, Deena A; Alalloush, Rahaf S; AlHemli, Haya A; Zeerak, Mohammad; Latif, Rabia; Ibrahim Al-Asoom, Lubna; Abdulrahman AlSunni, Ahmed; Mohammed Salem, Ayad; Alshurem, Mohammed; Aljaafari, Dana; Obaid, Shumaila; Alabdulhadi, Aseel","year":2024,"journal":"Journal of clinical medicine research, 16(11), 527-535","doi":"10.14740/jocmr6054","pmid":"39635334","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08886","title":"Contribution of hypothalamic orexin (hypocretin) circuits to pathologies of motivation.","authors":"Mohammadkhani, Aida; Mitchell, Caitlin; James, Morgan H; Borgland, Stephanie L; Dayas, Christopher V","year":2024,"journal":"British journal of pharmacology, 181(22), 4430-4449","doi":"10.1111/bph.17325","pmid":"39317446","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08887","title":"Identification of New Angiotensin-Converting Enzyme Inhibitory Peptides Isolated from the Hydrolysate of the Venom of Nemopilema nomurai Jellyfish.","authors":"Mohan Prakash, Ramachandran Loganathan; Ravi, Deva Asirvatham; Hwang, Du Hyeon; Kang, Changkeun; Kim, Euikyung","year":2024,"journal":"Toxins, 16(9)","doi":"10.3390/toxins16090410","pmid":"39330868","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08888","title":"Migraine treatment: Position paper of the French Headache Society.","authors":"Moisset, X; Demarquay, G; de Gaalon, S; Roos, C; Donnet, A; Giraud, P; Guégan-Massardier, E; Lucas, C; Mawet, J; Valade, D; Corand, V; Gollion, C; Moreau, N; Grangeon, L; Lantéri-Minet, M; Ducros, A","year":2024,"journal":"Revue neurologique, 180(10), 1087-1099","doi":"10.1016/j.neurol.2024.09.008","pmid":"39406556","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08889","title":"GLP-1 receptor agonists for weight reduction in people living with obesity but without diabetes: a living benefit-harm modelling study.","authors":"Moll, Hannah; Frey, Eliane; Gerber, Philipp; Geidl, Bettina; Kaufmann, Marco; Braun, Julia; Beuschlein, Felix; Puhan, Milo A; Yebyo, Henock G","year":2024,"journal":"EClinicalMedicine, 73, 102661","doi":"10.1016/j.eclinm.2024.102661","pmid":"38846069","tags":["glp-1","weight-management"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"For people with obesity but not diabetes, the benefits of GLP-1 agonists clearly outweighed the harms — but only if you're aiming for 10% or more weight loss. Among 1,000 people treated for 2 years, 375 more achieved 10% weight loss compared to placebo, with a 97% probability of net benefit at year 1 and 91% at year 2.\n\nHowever, aiming for just 5% weight loss did NOT show a net benefit (only 1% probability at year 2) because the cumulative side effects — nausea, vomiting, constipation, diarrhea, hair loss, gallstones — outweighed the modest weight loss. Among the drugs, semaglutide had the highest net benefit probability (96% at 2 years), followed by liraglutide (72%) and tirzepatide (60%). The study emphasizes that treatment decisions must be personalized based on individual goals and willingness to tolerate side effects.","whyItMatters":"This is one of the first rigorous benefit-harm analyses for GLP-1 drugs in non-diabetic obesity. While these drugs are often portrayed as miracle weight loss medications, this study quantifies the tradeoff: the side effects are real and substantial, and the net benefit only clearly materializes for people who achieve significant (10%+) weight loss. This has direct implications for prescribing decisions, patient expectations, and insurance coverage policies.","specificNumbers":"8 RCTs · n=8,847 · 74% women · 96% obese · Per 1,000 treated 2 years: 375 more achieved ≥10% weight loss · Side effects per 1,000: vomiting 110, constipation 118, diarrhea 100, alopecia 57, abdominal pain 41, gallstones 8, hypoglycemia 17 · Net benefit probability for 10% loss: 0.97 (yr 1), 0.91 (yr 2) · For 5% loss: 0.13 (yr 1), 0.01 (yr 2) · Semaglutide best: 0.96 at 2 years","methodology":"The researchers conducted a benefit-harm balance modeling study using data from 8 randomized controlled trials identified through systematic search of PubMed, trial registries, and regulatory documents. They performed pairwise meta-analysis to pool treatment effects, then predicted absolute outcomes over 1 and 2 years using exponential models. Patient preference weights (0 = least concerning to 1.0 = most concerning) were applied to each outcome, and the net benefit was calculated on a common scale accounting for statistical uncertainties in treatment effects, preference weights, and baseline risks.","limitations":"The analysis relies on trial data with maximum 2-year follow-up, so longer-term benefit-harm balance is unknown. Tirzepatide had limited trial data at the time of analysis, which may explain its lower net benefit probability despite strong weight loss efficacy. The preference weights used may not reflect every individual's priorities. Rare but serious adverse events (pancreatitis, thyroid cancer concerns) may not be adequately captured in trials of this size and duration."},{"rthcId":"RPEP-08890","title":"Bariatric and endo-bariatric interventions for diabetes: What is the current evidence?","authors":"Mondal, Sunetra; Ambrose Fistus, Vanessa; Pappachan, Joseph M","year":2024,"journal":"World journal of diabetes, 15(11), 2255-2263","doi":"10.4239/wjd.v15.i11.2255","pmid":"39582566","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08891","title":"Reducing the Impact of Headache and Allodynia Score in Chronic Migraine: An Exploratory Analysis from the Real-World Effectiveness of Anti-CGRP Monoclonal Antibodies Compared to Onabotulinum Toxin A (RAMO) Study.","authors":"Montisano, Danilo Antonio; Giossi, Riccardo; Canella, Mattia; Altamura, Claudia; Marcosano, Marilena; Vernieri, Fabrizio; Raggi, Alberto; Grazzi, Licia","year":2024,"journal":"Toxins, 16(4)","doi":"10.3390/toxins16040178","pmid":"38668603","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08892","title":"Calcitonin Gene-Related Peptide Inhibitors in the Treatment of Migraine in the Pediatric and Adolescent Populations: A Review.","authors":"Moore, Lisa; Pakalnis, Ann","year":2024,"journal":"Pediatric neurology, 157, 87-95","doi":"10.1016/j.pediatrneurol.2024.05.013","pmid":"38905744","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CGRP inhibitors are established as safe and effective for adult migraine treatment, and their use may be appropriate for pediatric patients in certain clinical situations. The review describes migraine pathophysiology as it relates to CGRP, provides an overview of available CGRP-targeting medications (both monoclonal antibodies and small-molecule antagonists), and discusses clinical usage considerations for children and adolescents. The limited evidence base for this population is a key theme.","whyItMatters":"Migraine is one of the most common neurological conditions in children, yet treatment options are severely limited. CGRP inhibitors have transformed adult migraine care, and many pediatric neurologists are already using them off-label for younger patients. This review provides a framework for evidence-based decision-making about when and how to use these peptide-targeted therapies in children.","specificNumbers":"","methodology":"Narrative literature review examining CGRP migraine pathophysiology, available CGRP inhibitor medications, and their clinical usage in pediatric and adolescent populations. Published in Pediatric Neurology.","limitations":"This is a narrative review, not a systematic review. The fundamental limitation is the lack of large randomized controlled trials of CGRP inhibitors specifically in pediatric populations. Most evidence is extrapolated from adult trials, with limited pediatric case series and off-label use data. Long-term safety in growing children is unknown. The review acknowledges that current evidence for pediatric use is limited."},{"rthcId":"RPEP-08893","title":"Non-steroidal mineralocorticoid antagonists and hyperkalemia monitoring in chronic kidney disease patients associated with type II diabetes: a narrative review.","authors":"Morales, Javier; Palmer, Biff F","year":2024,"journal":"Postgraduate medicine, 136(2), 111-119","doi":"10.1080/00325481.2024.2316572","pmid":"38344772","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08894","title":"Supported Supramolecular Hydrogel Nanoarchitectonics for Tunable Biocatalytic Flow Activity.","authors":"More, Shahaji H; Runser, Jean-Yves; Ontani, Aymeric; Fores, Jennifer Rodon; Carvalho, Alain; Blanck, Christian; Serra, Christophe A; Schmutz, Marc; Schaaf, Pierre; Jierry, Loïc","year":2024,"journal":"Small (Weinheim an der Bergstrasse, Germany), 20(51), e2405326","doi":"10.1002/smll.202405326","pmid":"39394755","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08895","title":"Pharmacologic Treatment of Obesity in adults and its impact on comorbidities: 2024 Update and Position Statement of Specialists from the Brazilian Association for the Study of Obesity and Metabolic Syndrome (Abeso) and the Brazilian Society of Endocrinology and Metabolism (SBEM).","authors":"Moreira, Rodrigo O; Valerio, Cynthia M; Hohl, Alexandre; Moulin, Cristiane; Moura, Fábio; Trujilho, Fábio R; Gerchman, Fernando; Correa, Livia L; Mancini, Marcio C; Melo, Maria Edna; Lamounier, Rodrigo N; van de Sande-Lee, Simone; Trujilho, Thaísa D G; Miranda, Paulo A C; Halpern, Bruno","year":2024,"journal":"Archives of endocrinology and metabolism, 68, e240422","doi":"10.20945/2359-4292-2024-0422","pmid":"39664998","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08896","title":"Delayed Type Hypersensitivity Reaction Induced By Liraglutide With Tolerance to Semaglutide.","authors":"Moreno-Borque, Ricardo; Guhl-Millán, Guillermo; Mera-Carreiro, Sara; Pazos-Guerra, Mario; Cortés-Toro, Jose Antonio; López-Bran, Eduardo","year":2024,"journal":"JCEM case reports, 2(6), luae105","doi":"10.1210/jcemcr/luae105","pmid":"38911363","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A 56-year-old female patient with class 3 obesity developed well-defined, round, erythematous pruriginous (itchy) plaques surrounding the injection site approximately 24 hours after each liraglutide (Saxenda) administration, beginning one month after starting treatment.\n\nThe delayed-type hypersensitivity reaction was confirmed through allergy testing and histopathological examination of the skin lesions. Despite this reaction to liraglutide, the patient tolerated semaglutide without hypersensitivity, indicating that the allergenic component was specific to liraglutide rather than common to all GLP-1 receptor agonists.","whyItMatters":"As GLP-1 receptor agonists are prescribed to millions of people for diabetes and obesity, allergic reactions — though uncommon — will inevitably occur. Clinicians need to know whether a patient allergic to one GLP-1 drug must avoid the entire class or can safely switch to an alternative. This case provides evidence that switching within the class is possible, which is clinically important given the transformative benefits of GLP-1 therapy.","specificNumbers":"","methodology":"This is a clinical case report. The diagnosis was established through clinical presentation (delayed erythematous plaques at injection sites), allergy testing (to confirm liraglutide as the causative agent), and histopathological study of the affected skin. The patient was subsequently transitioned to semaglutide to assess cross-reactivity.","limitations":"This is a single case report, so the finding of semaglutide tolerance in a liraglutide-allergic patient cannot be generalized to all patients. Delayed-type hypersensitivity reactions can vary in severity and mechanism between individuals. The specific component of liraglutide causing the reaction (the peptide backbone, fatty acid chain, or excipients) was not definitively identified. Long-term tolerance to semaglutide was not assessed."},{"rthcId":"RPEP-08897","title":"Cancer-Targeting Applications of Cell-Penetrating Peptides.","authors":"Moreno-Vargas, Liliana Marisol; Prada-Gracia, Diego","year":2024,"journal":"International journal of molecular sciences, 26(1)","doi":"10.3390/ijms26010002","pmid":"39795861","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08898","title":"Exploring the Chemical Features and Biomedical Relevance of Cell-Penetrating Peptides.","authors":"Moreno-Vargas, Liliana Marisol; Prada-Gracia, Diego","year":2024,"journal":"International journal of molecular sciences, 26(1)","doi":"10.3390/ijms26010059","pmid":"39795918","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08899","title":"A randomized, double-blind trial assessing the efficacy and safety of two doses of dulaglutide in Japanese participants with type 2 diabetes (AWARD-JPN).","authors":"Morioka, Tomoaki; Takeuchi, Masakazu; Ozeki, Akichika; Emoto, Masanori","year":2024,"journal":"Diabetes, obesity & metabolism, 26(8), 3167-3175","doi":"10.1111/dom.15644","pmid":"38715179","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"At 26 weeks, dulaglutide 1.5 mg was statistically superior to 0.75 mg for HbA1c reduction (LSM difference -0.29%, 95% CI: -0.43 to -0.14). At 52 weeks, the higher dose showed a significantly greater proportion reaching HbA1c <7.0% (46.3% vs 38.5%, p = 0.03) and greater fasting glucose reduction (LSM difference -9.4 mg/dL, 95% CI: -14.4 to -4.3, p < 0.001).\n\nNo statistically significant body weight change was observed in either arm. The most common adverse events were constipation (11.3%), diarrhea (9.6%), and fever (9.0%). Overall, 75.4% of participants experienced at least one treatment-emergent adverse event.","whyItMatters":"This trial establishes the benefit of the higher dulaglutide dose specifically for Japanese patients, who may respond differently to GLP-1 agonists due to differences in body composition, beta cell function, and diabetes pathophysiology compared to Western populations. The AWARD-JPN trial provides the evidence base needed for dosing recommendations in Japan's large type 2 diabetes population.","specificNumbers":"","methodology":"Phase 3, multicenter, randomized, double-blind, parallel-group study (AWARD-JPN, NCT04809220). 591 Japanese adults aged ≥20 with T2D for ≥6 months and inadequate glycemic control on a single oral medication were randomized to once-weekly dulaglutide 1.5 mg or 0.75 mg. Primary endpoint: mean HbA1c change at 26 weeks. Secondary endpoints assessed at 26 and 52 weeks. Intention-to-treat analysis.","limitations":"The study compared two doses of the same drug without a placebo arm, limiting conclusions about absolute efficacy. The absence of weight loss in both arms is unexplained and differs from Western dulaglutide trials. The study population was exclusively Japanese, limiting generalizability to other Asian or non-Asian populations. Duration was 52 weeks — longer-term data would be valuable. Participants were on a single oral antidiabetic drug at baseline, so results may not apply to those on more complex regimens."},{"rthcId":"RPEP-08900","title":"Retrospective Analysis of HLA Class II-Restricted Neoantigen Peptide-Pulsed Dendritic Cell Vaccine for Breast Cancer.","authors":"Morisaki, Takafumi; Kubo, Makoto; Morisaki, Shinji; Umebayashi, Masayo; Tanaka, Hiroto; Koya, Norihiro; Nakagawa, Shinichiro; Tsujimura, Kenta; Yoshimura, Sachiko; Kiyotani, Kazuma; Nakamura, Yusuke; Nakamura, Masafumi; Morisaki, Takashi","year":2024,"journal":"Cancers, 16(24)","doi":"10.3390/cancers16244204","pmid":"39766103","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08901","title":"Obesity management for the treatment of type 2 diabetes: emerging evidence and therapeutic approaches.","authors":"Morissette, Arianne; Mulvihill, Erin E","year":2024,"journal":"Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques, 27, 13065","doi":"10.3389/jpps.2024.13065","pmid":"38903652","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08902","title":"A Review on cLF36, a Novel Recombinant Antimicrobial Peptide-Derived Camel Lactoferrin.","authors":"Morovati, Solmaz; Baghkheirati, Amir Asghari; Sekhavati, Mohammad Hadi; Razmyar, Jamshid","year":2024,"journal":"Probiotics and antimicrobial proteins, 16(5), 1886-1905","doi":"10.1007/s12602-024-10285-5","pmid":"38722550","tags":["lactoferrin","antimicrobial-peptides","lactoferricin"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Researchers developed cLF36, a chimeric 42-amino acid peptide combining the complete camel lactoferrampin sequence with a partial lactoferricin sequence. Testing across multiple platforms showed broad-spectrum antimicrobial activity against human, avian, and plant bacterial pathogens. The peptide also demonstrated antiviral effects against hepatitis C virus, influenza virus, and rotavirus in computational and in vitro studies.\n\nNotably, cLF36 showed selective anticancer activity — higher toxicity against tumor cell lines than normal cells, potentially because it targets negatively charged glycosaminoglycans on tumor cell surfaces. The peptide showed no toxicity to host cells and demonstrated strong thermal and protease stability in serum, suggesting practical durability.","whyItMatters":"Antibiotic resistance is driving urgent demand for new antimicrobial approaches. cLF36 is interesting because it's derived from camel milk lactoferrin — an immune protein — and engineered to combine two active regions into a single more potent peptide. Its triple-threat activity (antibacterial, antiviral, anticancer) plus favorable safety and stability profile make it a promising candidate, though it remains in early research stages.","specificNumbers":"42-mer chimeric peptide · Active against human, avian, and plant pathogens · Antiviral vs HCV, influenza, rotavirus · Selective tumor cell toxicity · No host cell toxicity · Serum-stable","methodology":"Review of the research team's own multi-year body of work on cLF36, including in vitro antimicrobial testing, computational and in vitro antiviral assessments, cancer cell line studies, chicken feeding trials, and expression in prokaryotic (P170, pET) and eukaryotic (HEK293) systems.","limitations":"Most evidence is preclinical — in vitro, computational, or animal (chicken) models only. No human trials. Cost-effectiveness unknown. Pharmacokinetic and pharmacodynamic profiles not yet characterized. The review summarizes work primarily from a single research group."},{"rthcId":"RPEP-08903","title":"Cracking the Code: The Role of Peripheral Nervous System Signaling in Fracture Repair.","authors":"Morris, Ashlyn J; Parker, Reginald S; Nazzal, Murad K; Natoli, Roman M; Fehrenbacher, Jill C; Kacena, Melissa A; White, Fletcher A","year":2024,"journal":"Current osteoporosis reports, 22(1), 193-204","doi":"10.1007/s11914-023-00846-y","pmid":"38236511","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08904","title":"Improvement of Recalcitrant Folliculitis Decalvans With Tirzepatide: A Case Report.","authors":"Morrissette, Kali; Hansen, Stefan; Pavlis, Michelle; Murray, John C","year":2024,"journal":"Cureus, 16(12), e76267","doi":"10.7759/cureus.76267","pmid":"39845205","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08905","title":"Immunomodulation and inflammation: Role of GLP-1R and GIPR expressing cells within the gut.","authors":"Morrow, Nadya M; Morissette, Arianne; Mulvihill, Erin E","year":2024,"journal":"Peptides, 176, 171200","doi":"10.1016/j.peptides.2024.171200","pmid":"38555054","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies that GLP-1 receptors are expressed on multiple types of intraepithelial lymphocytes in the gut, including natural (TCRαβ and TCRγδ) and induced (TCRαβ+CD4+ and TCRαβ+CD8αβ+) populations. Both the body's own GLP-1 signaling and pharmacological GLP-1R activation influence local gut inflammation, systemic inflammation, the gut microbiome, whole-body metabolism, and GLP-1 bioavailability itself.\n\nGIPR signaling has been shown to affect the production of blood cells from bone marrow (hematopoiesis), but its specific role in gut immune function remains poorly understood. The authors also highlight a significant gap in the literature regarding how biological sex influences these signaling pathways.","whyItMatters":"GLP-1 receptor agonists (like semaglutide) and dual GLP-1R/GIPR agonists (like tirzepatide) are among the most widely prescribed medications for diabetes and obesity. This review highlights that these drugs may have important effects on gut immune function and inflammation that are not yet fully understood — effects that could be relevant to the millions of people currently taking them.","specificNumbers":"","methodology":"This is a narrative review synthesizing preclinical (animal model) and clinical evidence on GLP-1R and GIPR signaling in gut immunology. The authors examined published literature on incretin hormone receptors expressed on intestinal immune cells and their roles in inflammation and metabolism.","limitations":"As a narrative review, this paper synthesizes existing research rather than presenting new experimental data. The authors themselves note significant gaps in the literature, particularly around sex-based differences in GLP-1R and GIPR signaling. Much of the evidence comes from preclinical animal models, which may not fully translate to humans. The review does not include a systematic search methodology."},{"rthcId":"RPEP-08906","title":"Tumor-Targeted Cell-Penetrating Peptides Reveal That Monomethyl Auristatin E Temporally Modulates the Tumor Immune Microenvironment.","authors":"Mortaja, Mahsa; Cheng, Marcus M; Ali, Alina; Lesperance, Jacqueline; Hingorani, Dina V; Allevato, Mike M; Dhawan, Kanika; Camargo, Maria F; McKay, Rana R; Adams, Stephen R; Gutkind, J Silvio; Advani, Sunil J","year":2024,"journal":"Molecules (Basel, Switzerland), 29(23)","doi":"10.3390/molecules29235618","pmid":"39683778","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08907","title":"High-Caloric Diets in Adolescence Impair Specific GABAergic Subpopulations, Neurogenesis, and Alter Astrocyte Morphology.","authors":"Mota, Bárbara; Brás, Ana Rita; Araújo-Andrade, Leonardo; Silva, Ana; Pereira, Pedro A; Madeira, M Dulce; Cardoso, Armando","year":2024,"journal":"International journal of molecular sciences, 25(10)","doi":"10.3390/ijms25105524","pmid":"38791562","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08908","title":"Pichia pastoris secreted peptides crossing the blood-brain barrier and DSIP fusion peptide efficacy in PCPA-induced insomnia mouse models.","authors":"Mu, Xiaoxiao; Qu, Lijun; Yin, Liquan; Wang, Libo; Liu, Xiaoyang; Liu, Dingxi","year":2024,"journal":"Frontiers in pharmacology, 15, 1439536","doi":"10.3389/fphar.2024.1439536","pmid":"39444618","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08909","title":"Exploring the dipeptidyl peptidase-IV inhibitory potential of probiotic-fermented milk: An in vitro and in silico comprehensive investigation into peptides from milk of different farm animals.","authors":"Mudgil, Priti; Gan, Chee-Yuen; Yap, Pei-Gee; Redha, Ali Ali; Alsaadi, Reem H Sultan; Mohteshamuddin, Khaja; Aguilar-Toalá, José E; Vidal-Limon, Abraham M; Liceaga, Andrea M; Maqsood, Sajid","year":2024,"journal":"Journal of dairy science, 107(12), 10153-10173","doi":"10.3168/jds.2024-25108","pmid":"39122154","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08910","title":"Molecular docking studies on α-amylase inhibitory peptides from milk of different farm animals.","authors":"Mudgil, Priti; Al Dhaheri, Mouza Khamis Obaid; Alsubousi, Maitha Saif Mohammed; Khan, Hina; Redha, Ali Ali; Yap, Pei-Gee; Gan, Chee-Yuen; Maqsood, Sajid","year":2024,"journal":"Journal of dairy science, 107(5), 2633-2652","doi":"10.3168/jds.2023-24118","pmid":"38101739","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08911","title":"Risk of pancreatitis and pancreatic carcinoma for anti-diabetic medications: findings from real-world safety data analysis and systematic review and meta-analysis of randomized controlled trials.","authors":"Muhammed, Asif; Thomas, Christy; Kalaiselvan, Vivekanandan; Undela, Krishna","year":2024,"journal":"Expert opinion on drug safety, 23(6), 731-742","doi":"10.1080/14740338.2023.2284992","pmid":"37986140","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08912","title":"Long-term safety of zavegepant nasal spray for the acute treatment of migraine: A phase 2/3 open-label study.","authors":"Mullin, Kathleen; Croop, Robert; Mosher, Linda; Fullerton, Terence; Madonia, Jennifer; Lipton, Richard B","year":2024,"journal":"Cephalalgia : an international journal of headache, 44(8), 3331024241259456","doi":"10.1177/03331024241259456","pmid":"39210835","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08913","title":"Tirzepatide Immunogenicity on Pharmacokinetics, Efficacy, and Safety: Analysis of Data From Phase 3 Studies.","authors":"Mullins, Garrett R; Hodsdon, Michael E; Li, Ying Grace; Anglin, Greg; Urva, Shweta; Schneck, Karen; Bardos, Jennifer N; Martins, Ricardo Fonseca; Brown, Katelyn; Calderon, Boris","year":2024,"journal":"The Journal of clinical endocrinology and metabolism, 109(2), 361-369","doi":"10.1210/clinem/dgad532","pmid":"37700637","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08914","title":"Toxin-derived peptides: An unconventional approach to alleviating cerebral stroke burden and neurobehavioral impairments.","authors":"Mumtaz, Sayed Md; Khan, Mohammad Ahmed; Jamal, Azfar; Hattiwale, Shaheenkousar H; Parvez, Suhel","year":2024,"journal":"Life sciences, 351, 122777","doi":"10.1016/j.lfs.2024.122777","pmid":"38851419","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08915","title":"SGLT-2 Inhibitors' and GLP-1 Receptor Agonists' Influence on Neuronal and Glial Damage in Experimental Stroke.","authors":"Murasheva, Anna; Fuks, Oksana; Timkina, Natalya; Mikhailova, Arina; Vlasov, Timur; Samochernykh, Konstantin; Karonova, Tatiana","year":2024,"journal":"Biomedicines, 12(12)","doi":"10.3390/biomedicines12122797","pmid":"39767704","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In non-diabetic rats (n=10 per group):\n- All drugs (empagliflozin, canagliflozin, dulaglutide) reduced brain infarct size more effectively than metformin\n- Dulaglutide improved neurological status better than both metformin and SGLT2 inhibitors\n- All drugs reduced neurofilament light chains (NLC) and neuronal damage markers; none reduced glial marker S100BB\n\nIn diabetic rats:\n- All drugs had infarct-limiting effects and reduced neurological deficits\n- Untreated diabetic rats had the worst neurological outcomes\n- Dulaglutide and empagliflozin (but not canagliflozin) also decreased the glial damage marker S100BB\n- None affected neuron-specific enolase\n\nConclusion: GLP-1RA may be more neuroprotective than SGLT2i overall, with benefits on both neuronal and glial damage.","whyItMatters":"Stroke is a leading cause of death and disability, and diabetic patients face double the stroke risk. Finding that a GLP-1 peptide agonist provides superior brain protection compared to other diabetes drugs opens the possibility that drug choice for diabetic patients could be guided not just by glucose control but also by stroke risk reduction. The mechanistic data on neuronal versus glial protection adds depth to understanding how these drugs work in the brain.","specificNumbers":"","methodology":"Non-diabetic Wistar rats (5 groups, n=10 each) received empagliflozin, canagliflozin, dulaglutide, metformin, or saline for 7 days before induced stroke. At 48 hours post-stroke, neurological deficit, brain damage volume, and biomarkers (NLC, S100BB, neuron-specific enolase) were assessed. A parallel experiment used diabetic rats (high-fat diet + nicotinamide/streptozotocin model) with 8 weeks of drug treatment before stroke induction.","limitations":"This is a rat study using induced stroke models that may not fully replicate human stroke pathophysiology. The sample size (n=10 per group) is standard for animal studies but limits statistical power. The drugs were given before stroke (pretreatment), which does not reflect clinical scenarios where treatment typically begins after stroke onset. Only one GLP-1RA (dulaglutide) was tested — results may differ for semaglutide or liraglutide. The 48-hour assessment window may not capture long-term outcomes."},{"rthcId":"RPEP-08916","title":"Antagonist of Growth Hormone-Releasing Hormone Receptor MIA-690 Suppresses the Growth of Androgen-Independent Prostate Cancers.","authors":"Muñoz-Moreno, Laura; Gómez-Calcerrada, M Isabel; Arenas, M Isabel; Carmena, M José; Prieto, Juan C; Schally, Andrew V; Bajo, Ana M","year":2024,"journal":"International journal of molecular sciences, 25(20)","doi":"10.3390/ijms252011200","pmid":"39456984","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The GHRH receptor antagonist peptide MIA-690 showed synergistic antitumor effects when combined with the EGFR inhibitor gefitinib in castration-resistant prostate cancer (CRPC) PC-3 cells. The combination inhibited cell viability, adhesion, and metalloprotease activity more effectively than either agent alone, and induced cell cycle arrest. These effects were confirmed in vivo in nude mice bearing PC-3 tumors 36 days after inoculation, demonstrating that blocking GHRH-R/EGFR crosstalk is a viable strategy against treatment-resistant prostate cancer.","whyItMatters":"Castration-resistant prostate cancer is notoriously difficult to treat because tumors find alternative survival pathways. This study reveals that GHRH receptors can transactivate EGFR signaling, providing a survival escape route, and shows that a peptide antagonist can block this crosstalk — opening a potential new combination therapy approach for advanced prostate cancer.","specificNumbers":"PC-3 cell line · synergistic effect of MIA-690 + gefitinib · 36-day nude mouse tumor model · inhibited viability, adhesion, and metalloprotease activity","methodology":"In vitro experiments used PC-3 castration-resistant prostate cancer cells treated with MIA-690 (GHRH-R antagonist) and/or gefitinib (EGFR inhibitor). Researchers assessed cell viability, adhesion, gelatinolytic (metalloprotease) activity, and cell cycle progression. In vivo validation used subcutaneous PC-3 tumor xenografts in athymic nude mice evaluated 36 days post-inoculation.","limitations":"PC-3 is a single cell line model of CRPC; other CRPC cell lines and patient-derived models were not tested. The nude mouse xenograft model lacks a functional immune system, which limits translation to immunocompetent settings. Specific dosing, tumor size measurements, and statistical details are not provided in the abstract."},{"rthcId":"RPEP-08917","title":"Pharmacotherapy of Weight-loss and Obesity with a Focus on GLP 1-Receptor Agonists.","authors":"Myerson, Merle; Paparodis, Rodis D","year":2024,"journal":"Journal of clinical pharmacology, 64(10), 1204-1221","doi":"10.1002/jcph.2487","pmid":"38924121","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08918","title":"Dynamic regulation of CeA gene expression during acute and protracted abstinence from chronic binge drinking of male and female C57BL/6J mice.","authors":"Méndez, Hernán G; Neira, Sofia; Flanigan, Meghan E; Haun, Harold L; Boyt, Kristen M; Thiele, Todd E; Kash, Thomas L","year":2024,"journal":"Alcohol (Fayetteville, N.Y.), 120, 179-193","doi":"10.1016/j.alcohol.2024.06.005","pmid":"38945280","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"During acute abstinence (1 day), male mice had upregulated NPY, somatostatin (Sst), and NPY receptor Y2 (Npy2r) in the CeA, while females showed upregulated GABA receptor subunit alpha 2 (Gabra2) and the peptidase angiotensinase C (Prcp). Males also had downregulated NMDA receptor subunit Grin1.\n\nDuring protracted abstinence (7 days), male mice maintained elevated Npy2r, NPY, and somatostatin expression. Female mice showed increased corticotropin-releasing hormone (CRH) and NPY expression. The gene expression profiles differed significantly between sexes at both time points, suggesting sex-specific neuropeptide responses to binge alcohol exposure and withdrawal.","whyItMatters":"Alcohol use disorder affects men and women differently, yet most neuroscience research has historically focused on males. This study reveals that the neuropeptide systems in the brain's emotional center respond to binge drinking and withdrawal in sex-specific ways. Understanding these differences is critical for developing targeted treatments — a drug that modulates NPY signaling, for example, might work differently in men versus women. The involvement of stress-related peptides like CRH specifically in female mice also suggests different vulnerability pathways.","specificNumbers":"","methodology":"Two separate cohorts of C57BL/6J mice underwent the 'drinking in the dark' (DID) binge drinking protocol. Central amygdala (CeA) brain tissue was collected at 1 day (acute) and 7 days (protracted) abstinence after DID. Quantitative reverse-transcription PCR (qRT-PCR) was used to measure relative gene expression changes of 25 genes related to G protein-coupled receptors, neuropeptides, ion channel subunits, and enzymes previously implicated in alcohol use disorder.","limitations":"This is a mouse study, and neuropeptide expression patterns may differ in human brains. Only gene expression (mRNA) was measured, not protein levels or functional neuropeptide activity. The DID model represents binge drinking specifically and may not capture other patterns of alcohol consumption. Only two time points (1 and 7 days) were assessed, missing potential dynamic changes between and beyond these windows. The number of mice per group is not specified in the abstract."},{"rthcId":"RPEP-08919","title":"Dose escalation study of a personalized peptide-based neoantigen vaccine (EVX-01) in patients with metastatic melanoma.","authors":"Mørk, Sofie Kirial; Skadborg, Signe Koggersbøl; Albieri, Benedetta; Draghi, Arianna; Bol, Kalijn; Kadivar, Mohammad; Westergaard, Marie Christine Wulff; Stoltenborg Granhøj, Joachim; Borch, Annie; Petersen, Nadia Viborg; Thuesen, Nikolas; Rasmussen, Ida Svahn; Andreasen, Lars Vibe; Dohn, Rebecca Bach; Yde, Christina Westmose; Noergaard, Nis; Lorentzen, Torben; Soerensen, Anders Bundgaard; Kleine-Kohlbrecher, Daniela; Jespersen, Anders; Christensen, Dennis; Kringelum, Jens; Donia, Marco; Hadrup, Sine Reker; Marie Svane, Inge","year":2024,"journal":"Journal for immunotherapy of cancer, 12(5)","doi":"10.1136/jitc-2024-008817","pmid":"38782542","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08920","title":"Potent incretin-based therapy for obesity: A systematic review and meta-analysis of the efficacy of semaglutide and tirzepatide on body weight and waist circumference, and safety.","authors":"Müllertz, Alberte Laura Oest; Sandsdal, Rasmus Michael; Jensen, Simon Birk Kjær; Torekov, Signe Sørensen","year":2024,"journal":"Obesity reviews : an official journal of the International Association for the Study of Obesity, 25(5), e13717","doi":"10.1111/obr.13717","pmid":"38463003","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across seven RCTs (n=5,140), the overall placebo-subtracted weight loss was 15.0% (95% CI: -17.8 to -12.2). When broken down by drug:\n\n- Semaglutide 2.4 mg weekly (5 studies, n=3,288): -12.9% weight loss (95% CI: -14.7 to -11.1), -9.7 cm waist circumference reduction (95% CI: -10.8 to -8.5)\n- Tirzepatide 10 or 15 mg weekly (2 studies, n=1,852): -19.2% weight loss (95% CI: -22.2 to -16.2), -14.6 cm waist circumference reduction (95% CI: -15.8 to -13.4)\n\nAdverse events were primarily gastrointestinal, mild to moderate in severity, most frequent during dose titration, and leveled off during maintenance treatment.","whyItMatters":"This meta-analysis provides the most comprehensive pooled comparison of the two leading incretin-based obesity treatments to date. With over 5,000 patients, it gives clinicians stronger evidence to guide treatment decisions and helps quantify the magnitude of weight loss patients can expect from each drug.","specificNumbers":"","methodology":"This was a systematic review and meta-analysis following standard methodology. From 744 identified records, seven randomized controlled trials were included — five studying semaglutide 2.4 mg and two studying tirzepatide 10 or 15 mg — all in people with obesity without diabetes. Primary outcomes were placebo-subtracted changes in body weight and waist circumference, with safety assessed across all trials.","limitations":"The comparison between semaglutide and tirzepatide is indirect, as no head-to-head RCTs were included. Only two tirzepatide trials were available compared to five for semaglutide. All studies excluded people with diabetes, limiting generalizability. Trial durations and populations varied across studies, and long-term outcomes beyond the study periods were not assessed."},{"rthcId":"RPEP-08921","title":"Novel Insights into Diabetic Kidney Disease.","authors":"Młynarska, Ewelina; Buławska, Dominika; Czarnik, Witold; Hajdys, Joanna; Majchrowicz, Gabriela; Prusinowski, Filip; Stabrawa, Magdalena; Rysz, Jacek; Franczyk, Beata","year":2024,"journal":"International journal of molecular sciences, 25(18)","doi":"10.3390/ijms251810222","pmid":"39337706","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08922","title":"Rational design of hybrid peptide with high antimicrobial property derived from Melittin and Lasioglossin.","authors":"Nabizadeh, Somayeh; Rahbarnia, Leila; Nowrozi, Jamileh; Farajnia, Safar; Hosseini, Farzaneh","year":2024,"journal":"Journal of biomolecular structure & dynamics, 42(23), 13091-13099","doi":"10.1080/07391102.2023.2274971","pmid":"37885265","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08923","title":"Effects of glucagon-like peptide-1 receptor agonists on upper endoscopy in diabetic and nondiabetic patients.","authors":"Nadeem, Danial; Taye, Mahdi; Still, Matthew D; McShea, Shannon; Satterfield, Daniel; Dove, James T; Wood, G Craig; Addissie, Benyam D; Diehl, David L; Johal, Amitpal S; Khara, Harshit S; Confer, Bradley D; Still, Christopher D","year":2024,"journal":"Gastrointestinal endoscopy, 100(4), 745-749","doi":"10.1016/j.gie.2024.04.2900","pmid":"38692518","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08924","title":"Presence of Modified Peptides with High Bioavailability and Angiotensin-Converting Enzyme Inhibitory Activity in Japanese Fermented Soybean Paste (Miso).","authors":"Nagao, Atsuya; Nakamoto, Yoko; Miyauchi, Satoshi; Sato, Kenji","year":2024,"journal":"Journal of agricultural and food chemistry, 72(34), 18942-18956","doi":"10.1021/acs.jafc.4c02603","pmid":"39145497","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08925","title":"Prognostic Value of Left Ventricular Myocardial Strain Parameters Derived from Cardiac Magnetic Resonance Feature Tracking Technique in Light-Chain Cardiac Amyloidosis Patients: A Pilot Study.","authors":"Nai, Rile; Liu, Jia; Zhao, Kai; Ma, Shuai; Ma, Wei; He, Jiangkai; Xu, Shasha; Lian, Jianxiu; Li, Wei; Qiu, Jianxing","year":2024,"journal":"Reviews in cardiovascular medicine, 25(11), 400","doi":"10.31083/j.rcm2511400","pmid":"39618870","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08926","title":"Computational exploration of naturally derived peptides inhibitory mechanisms against ACE enzyme, from interactions to structural-dynamics.","authors":"Najafpour, Reza; Ghasemi, Ashraf-Sadat; Dehghanbanadaki, N; Mehralitabar, Havva","year":2024,"journal":"Biochemical and biophysical research communications, 735, 150812","doi":"10.1016/j.bbrc.2024.150812","pmid":"39437699","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08927","title":"Intracellular Delivery of Plasmid DNA Using Amphipathic Helical Cell-Penetrating Peptides Containing Dipropylglycine.","authors":"Naka, Motoki; Umeno, Tomohiro; Shibuya, Mika; Yamaberi, Yuto; Ueda, Atsushi; Tanaka, Masakazu; Takemoto, Hiroyasu; Oba, Makoto","year":2024,"journal":"Chemical & pharmaceutical bulletin, 72(5), 512-517","doi":"10.1248/cpb.c24-00221","pmid":"38811213","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08928","title":"Ovomemolins: Egg-derived peptides that improved cognitive decline after oral administration in mice.","authors":"Nakajima, Takanobu; Shobako, Maiko; Kaneko, Kentaro; Kurabayashi, Atsushi; Sato, Masaru; Ohinata, Kousaku","year":2024,"journal":"FASEB bioAdvances, 6(7), 177-188","doi":"10.1096/fba.2023-00149","pmid":"38974115","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08929","title":"Increased LL37 in psoriasis and other inflammatory disorders promotes LDL uptake and atherosclerosis.","authors":"Nakamura, Yoshiyuki; Kulkarni, Nikhil N; Takahashi, Toshiya; Alimohamadi, Haleh; Dokoshi, Tatsuya; Liu, Edward; Shia, Michael; Numata, Tomofumi; Luo, Elizabeth Wc; Gombart, Adrian F; Yang, Xiaohong; Secrest, Patrick; Gordts, Philip Lsm; Tsimikas, Sotirios; Wong, Gerard Cl; Gallo, Richard L","year":2024,"journal":"The Journal of clinical investigation, 134(5)","doi":"10.1172/JCI172578","pmid":"38194294","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"LL37 enhanced LDL uptake in macrophages through three receptors: LDLR, SR-B1, and CD36. This increased cytosolic cholesterol in macrophages and altered lipid metabolism gene expression in ways consistent with cholesterol overloading — the key process driving foam cell formation and atherosclerotic plaque development.\n\nStructural analysis using synchrotron x-ray scattering revealed how LL37 binds LDL particles and facilitates receptor interactions. Critically, this LDL uptake function is unique to human and some primate cathelicidins — it was not observed with mouse or rabbit versions of the peptide, which may explain why standard animal models haven't captured this mechanism. ApoE-knockout mice engineered to express human LL37 developed larger atherosclerotic plaques than controls. In humans with cardiovascular disease, plasma LL37 levels positively correlated with oxidized phospholipids on apolipoprotein B — a validated biomarker of atherosclerotic disease.","whyItMatters":"This study solves a clinical mystery that has puzzled cardiologists and dermatologists for years: why do patients with psoriasis, lupus, and other inflammatory conditions develop heart disease at much higher rates? The answer involves a peptide that the immune system overproduces during chronic inflammation — creating an unexpected bridge between the innate immune system and cardiovascular disease. This could lead to new biomarkers for heart disease risk in inflammatory conditions and potential therapeutic targets.","specificNumbers":"","methodology":"This was a multi-approach translational study combining in vitro cell biology (macrophage LDL uptake assays), structural biology (synchrotron small-angle x-ray scattering of LL37-LDL complexes), comparative biology (testing cathelicidins from humans, primates, mice, and rabbits), in vivo atherosclerosis modeling (ApoE-knockout mice expressing human LL37), and clinical correlation (measuring LL37 and OxPL-apoB in human cardiovascular disease patients). Published in the Journal of Clinical Investigation.","limitations":"The in vivo atherosclerosis data comes from a mouse model (ApoE-knockout mice), which, while standard, does not perfectly replicate human atherosclerosis. The human correlation between LL37 and OxPL-apoB was observational and cannot prove causation. The study demonstrated the mechanism in macrophages but did not show that blocking LL37 reduces atherosclerosis. The species-specific nature of the finding (human LL37 only) means that decades of mouse cathelicidin research may have missed this pathway entirely."},{"rthcId":"RPEP-08930","title":"Tachycardia-Induced Cardiomyopathy Following Prolonged Ritodrine Infusion During Pregnancy: A Case Report.","authors":"Nakao, Masahiro; Izawa, Miho; Takamisawa, Itaru; Horiuchi, Chinami; Ohmori, Azumi; Katsuragi, Shinji","year":2024,"journal":"Cureus, 16(12), e76465","doi":"10.7759/cureus.76465","pmid":"39867041","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08931","title":"GLP-1 receptor agonists may enhance the effects of desmopressin in individuals with AVP deficiency: a case series and proposed mechanism.","authors":"Nakhleh, Afif; Shehadeh, Naim; Mansour, Bshara","year":2024,"journal":"Pituitary, 27(5), 731-736","doi":"10.1007/s11102-024-01451-7","pmid":"39240512","tags":["glp-1-agonists","drug-interactions","vasopressin"],"studyType":"Case Series","evidenceStrength":"Preliminary","keyFinding":"Three patients with AVP deficiency (diabetes insipidus) who were on stable desmopressin therapy needed to reduce their desmopressin doses after starting GLP-1 receptor agonists for diabetes or obesity. The GLP-1 drugs decreased thirst perception and altered sodium and water handling, effectively enhancing the effects of their existing desmopressin therapy.\n\nThe proposed mechanism: GLP-1 RAs induce natriuresis (increased sodium excretion) and increase distal fluid delivery to the kidneys' collecting ducts. In patients with AVP deficiency taking desmopressin, this means the same dose of desmopressin now concentrates urine more effectively — requiring a lower dose to maintain normal water balance. All three patients maintained normal thirst and urine output on the reduced desmopressin doses.","whyItMatters":"As millions of people start GLP-1 drugs, clinicians need to know about unexpected interactions with other medications. This case series reveals that GLP-1 drugs can alter water and sodium balance significantly enough to require desmopressin dose adjustments in patients with diabetes insipidus. Without recognizing this interaction, patients could develop dangerously low sodium levels (hyponatremia) from relatively too much desmopressin. This is a clinically actionable finding.","specificNumbers":"3 patients · all on stable desmopressin · all required dose reduction after GLP-1 RA · mechanisms: decreased thirst + natriuresis + altered distal fluid delivery","methodology":"Retrospective case series of three patients with AVP deficiency (central diabetes insipidus) on stable desmopressin therapy who were started on GLP-1 receptor agonists for type 2 diabetes or obesity. Clinical outcomes (thirst, urine output, desmopressin dose changes) were documented and a physiological mechanism was proposed.","limitations":"Only three patients — a very small case series that cannot establish causation or quantify the interaction's magnitude. The specific GLP-1 RA used and the extent of desmopressin dose reduction are not detailed in the abstract. The proposed mechanism is theoretical and has not been experimentally validated. Weight loss itself (independent of GLP-1 drug effects) could contribute to altered fluid balance. Prospective studies are needed to confirm this interaction."},{"rthcId":"RPEP-08932","title":"Imaging of Myocardial αvβ3 Integrin Expression for Evaluation of Myocardial Injury After Acute Myocardial Infarction.","authors":"Nammas, Wail; Paunonen, Christian; Teuho, Jarmo; Siekkinen, Reetta; Luoto, Pauliina; Käkelä, Meeri; Hietanen, Ari; Viljanen, Tapio; Dietz, Matthieu; Prior, John O; Li, Xiang-Guo; Roivainen, Anne; Knuuti, Juhani; Saraste, Antti","year":2024,"journal":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 65(1), 132-138","doi":"10.2967/jnumed.123.266148","pmid":"37973184","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08933","title":"The impact of GLP-1 receptor agonist shortages on glycaemic Control: Findings from an Australian specialist diabetes clinic.","authors":"Nanayakkara, Natalie; Lh Huang, Michael; Jenkins, Alicia J; Cohen, Neale D","year":2024,"journal":"Diabetes research and clinical practice, 213, 111740","doi":"10.1016/j.diabres.2024.111740","pmid":"38852625","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 811 adults with type 2 diabetes at an Australian specialist diabetes clinic, median HbA1c levels significantly increased by 0.3% during a period when GLP-1 receptor agonist medications were in short supply. The analysis covered prescriptions from January 2019 through October 2023, comparing outcomes before and during the shortage period.\n\nA 0.3% rise in HbA1c is clinically meaningful — it reflects worsening blood sugar control that, if sustained, increases the risk of diabetes-related complications including cardiovascular disease, kidney damage, and nerve problems.","whyItMatters":"GLP-1 receptor agonists have become cornerstone treatments for type 2 diabetes, but surging demand — partly driven by their use for weight loss — has created global shortages. This study provides real-world evidence that these shortages translate directly into worse health outcomes for diabetes patients who depend on these medications, highlighting the urgent need for stable drug supply chains.","specificNumbers":"","methodology":"The researchers conducted a retrospective analysis of medical records from 811 adults with type 2 diabetes attending a specialist diabetes clinic in Australia. They identified patients who had received at least two GLP-1 receptor agonist prescriptions both before and during the medication shortage period (January 2019 to October 2023) and compared their HbA1c levels across these time periods.","limitations":"The study was conducted at a single specialist diabetes clinic in Australia, which may not reflect outcomes at primary care settings or in other countries. The retrospective design means the researchers could not control for other factors that may have influenced blood sugar changes during the shortage period, such as patients switching to alternative medications or lifestyle changes. The abstract does not detail what patients did when they could not access their GLP-1 RA prescriptions."},{"rthcId":"RPEP-08934","title":"Changes in gene expression due to aging in the hypothalamus of mice.","authors":"Narukawa, Masataka; Saito, Yoshikazu; Kasahara, Yoichi; Asakura, Tomiko; Misaka, Takumi","year":2024,"journal":"Neuroreport, 35(15), 987-991","doi":"10.1097/WNR.0000000000002092","pmid":"39166393","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08935","title":"Decreased risk of recurrent acute pancreatitis with semaglutide and tirzepatide in people with type 2 diabetes or obesity with a history of acute pancreatitis: A propensity matched global federated TriNetX database-based retrospective cohort study.","authors":"Nassar, Mahmoud; Nassar, Omar; Abosheaishaa, Hazem; Misra, Anoop","year":2024,"journal":"Diabetes & metabolic syndrome, 18(9), 103116","doi":"10.1016/j.dsx.2024.103116","pmid":"39332263","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08936","title":"GLP-1 receptor agonists and their role in managing type 2 diabetes.","authors":"Nazarko, Linda","year":2024,"journal":"British journal of community nursing, 29(8), 391-396","doi":"10.12968/bjcn.2024.0089","pmid":"39072740","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08937","title":"Efficacy and Tolerability of Erenumab and Topiramate for Prevention of Chronic Migraine: A Retrospective Cohort Study.","authors":"Nebrisi, Eslam El; Ruwayya, Zainaba Suaad Ahmed; Alzayori, Dalya Ibrahim; Alzayori, Ranya Ibrahim; Chandran, Shyam Babu; Elshafei, Mohamed","year":2024,"journal":"Medicina (Kaunas, Lithuania), 60(10)","doi":"10.3390/medicina60101684","pmid":"39459471","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08938","title":"Intrapatient Changes in CT-Based Body Composition After Initiation of Semaglutide (Glucagon-Like Peptide-1 Receptor Agonist) Therapy.","authors":"Nelson, Leslie W; Lee, Matthew H; Garrett, John W; Pickhardt, Silas G; Warner, Joshua D; Summers, Ronald M; Pickhardt, Perry J","year":2024,"journal":"AJR. American journal of roentgenology, 223(6), e2431805","doi":"10.2214/AJR.24.31805","pmid":"39230989","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08939","title":"Neuropeptide Y and Pain: Insights from Brain Research.","authors":"Nelson, Tyler S; Allen, Heather N; Khanna, Rajesh","year":2024,"journal":"ACS pharmacology & translational science, 7(12), 3718-3728","doi":"10.1021/acsptsci.4c00333","pmid":"39698268","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08940","title":"Meningeal lymphatic CGRP signaling governs pain via cerebrospinal fluid efflux and neuroinflammation in migraine models.","authors":"Nelson-Maney, Nathan P; Bálint, László; Beeson, Anna Ls; Serafin, D Stephen; Kistner, Bryan M; Douglas, Elizabeth S; Siddiqui, Aisha H; Tauro, Alyssa M; Caron, Kathleen M","year":2024,"journal":"The Journal of clinical investigation, 134(15)","doi":"10.1172/JCI175616","pmid":"38743922","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08941","title":"Relationship between residual gastric content and peri-operative semaglutide use assessed by gastric ultrasound: a prospective observational study.","authors":"Nersessian, Rafael S F; da Silva, Leopoldo M; Carvalho, Marco Aurélio S; Silveira, Saullo Q; Abib, Arthur C V; Bellicieri, Fernando N; Lima, Helidea O; Ho, Anthony M-H; Anjos, Gabriel S; Mizubuti, Glenio B","year":2024,"journal":"Anaesthesia, 79(12), 1317-1324","doi":"10.1111/anae.16454","pmid":"39435967","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08942","title":"The prostaglandin E2 EP3 receptor has disparate effects on islet insulin secretion and content in β-cells in a high-fat diet-induced mouse model of obesity.","authors":"Neuman, Joshua C; Reuter, Austin; Carbajal, Kathryn A; Schaid, Michael D; Kelly, Grant; Connors, Kelsey; Kaiser, Cecilia; Krause, Joshua; Hurley, Liam D; Olvera, Angela; Davis, Dawn Belt; Wisinski, Jaclyn A; Gannon, Maureen; Kimple, Michelle E","year":2024,"journal":"American journal of physiology. Endocrinology and metabolism, 326(5), E567-E576","doi":"10.1152/ajpendo.00061.2023","pmid":"38477664","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08943","title":"Structural basis of inhibition of human NaV1.8 by the tarantula venom peptide Protoxin-I.","authors":"Neumann, Bryan; McCarthy, Stephen; Gonen, Shane","year":2024,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2024.08.27.609828","pmid":"39253517","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08944","title":"Contractile Effects of Semaglutide in the Human Atrium.","authors":"Neumann, Joachim; Hadová, Katarína; Klimas, Jan; Hofmann, Britt; Gergs, Ulrich","year":2024,"journal":"Pharmaceutics, 16(9)","doi":"10.3390/pharmaceutics16091139","pmid":"39339176","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide produced a concentration- and time-dependent positive inotropic effect (increased contraction force) in isolated human right atrial preparations obtained during open-heart surgery. The effect was accompanied by increased rates of tension development and relaxation, plus reduced muscle relaxation time.\n\nMechanistically, the positive inotropic effect was attenuated by H89 (a cAMP-dependent protein kinase inhibitor) and by ryanodine (an inhibitor of sarcoplasmic calcium release), indicating the effect is mediated through the cAMP/PKA pathway and intracellular calcium handling. Notably, semaglutide up to 100 nM failed to produce a positive inotropic effect in mouse left atrial preparations, highlighting a species-specific response.","whyItMatters":"With millions of patients taking semaglutide for diabetes and obesity, understanding its direct cardiac effects is critical. GLP-1 receptor agonists have shown cardiovascular benefits in clinical trials, but whether they act directly on heart muscle or only indirectly through metabolic improvements has been unclear. This study provides the first evidence that semaglutide directly increases human heart contractility at therapeutic concentrations — a finding with important implications for patients with heart failure.","specificNumbers":"","methodology":"Ex vivo contraction experiments using isolated human right atrial muscle preparations obtained from patients undergoing open-heart surgery. Tissue strips were exposed to increasing concentrations of semaglutide while measuring force of contraction, rates of tension development and relaxation. Pharmacological inhibitors (H89, ryanodine) were used to probe the signaling mechanism. Mouse left atrial preparations were tested for comparison.","limitations":"This was an ex vivo study on isolated tissue strips, which doesn't capture the complexity of an intact beating heart with neural and hormonal inputs. Tissue was from surgical patients who likely had preexisting cardiac conditions, which may not represent healthy hearts. The effect was not seen in mouse tissue, making preclinical animal modeling difficult. The functional significance of the observed inotropic effect in the context of whole-heart function and clinical outcomes is unknown. Only atrial tissue was tested — ventricular effects remain unstudied."},{"rthcId":"RPEP-08945","title":"Evidence That a Peptide-Drug/p53 Gene Complex Promotes Cognate Gene Expression and Inhibits the Viability of Glioblastoma Cells.","authors":"Neves, Ana; Albuquerque, Tânia; Faria, Rúben; Santos, Cecília R A; Vivès, Eric; Boisguérin, Prisca; Carneiro, Diana; Bruno, Daniel F; Pavlaki, Maria D; Loureiro, Susana; Sousa, Ângela; Costa, Diana","year":2024,"journal":"Pharmaceutics, 16(6)","doi":"10.3390/pharmaceutics16060781","pmid":"38931902","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08946","title":"Glucagon-like peptide-1 receptor agonists for treatment of diabetes and obesity: advantage of oral delivery.","authors":"New, R R C; Bogus, M; Travers, G N; Hahn, U; Vaiceliunaite, A; Burnet, M; Wang, J H; Wen, H","year":2024,"journal":"Frontiers in drug delivery, 4, 1456654","doi":"10.3389/fddev.2024.1456654","pmid":"40836975","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The Axcess oral peptide delivery formulation achieved biopotencies of 9% for exendin-4 and 14.8% for semaglutide in preclinical models — meaning these percentages of the orally administered peptide reached the bloodstream in active form and produced measurable changes in insulin and glucose levels. The oral route delivers peptides to interact with GLP-1 receptors on vagal afferents in the intestine, mimicking how the body's own GLP-1 naturally works.","whyItMatters":"Most GLP-1 drugs require injection, which many patients dislike. While oral semaglutide (Rybelsus) exists, it requires high doses because very little peptide survives the digestive tract. Axcess technology achieves much higher oral bioavailability (14.8% for semaglutide vs ~1% for Rybelsus), which could enable lower oral doses, potentially reducing side effects and cost. More efficient oral delivery could make GLP-1 peptide therapy accessible to far more patients worldwide.","specificNumbers":"Exendin-4: 9% oral biopotency · semaglutide: 14.8% oral biopotency · insulin and glucose changes measured · intestinal GLP-1R interaction via vagal afferents · Axcess™ formulation","methodology":"The Axcess oral peptide delivery formulation was tested with two GLP-1 receptor agonists (exendin-4 and semaglutide) in preclinical models. Oral administration was compared to injectable doses by measuring changes in blood insulin and glucose levels to determine biopotency (the fraction of orally delivered peptide that produces a biological effect equivalent to injection).","limitations":"These are preclinical data and oral bioavailability in humans may differ significantly. The specific animal models and detailed experimental conditions were not fully described in the abstract. Long-term safety of the Axcess formulation components was not addressed. Comparison with the existing oral semaglutide technology (SNAC enhancer used in Rybelsus) was not directly made. Manufacturing feasibility and stability of the formulation need evaluation."},{"rthcId":"RPEP-08947","title":"The role of glucagon-like peptide 1 receptor agonists for weight control in individuals with acquired hypothalamic obesity-A systematic review.","authors":"Ng, Victoria Wen Wei; Gerard, Gheslynn; Koh, Jonathan Jin Kai; Loke, Kah Yin; Lee, Yung Seng; Ng, Nicholas Beng Hui","year":2024,"journal":"Clinical obesity, 14(3), e12642","doi":"10.1111/cob.12642","pmid":"38273176","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08948","title":"Antioxidant Peptides and Protein Hydrolysates from Tilapia: Cellular and In Vivo Evidences for Human Health Benefits.","authors":"Ng, Wen-Jie; Wong, Fai-Chu; Abd Manan, Fazilah; Chow, Yit-Lai; Ooi, Ai-Lin; Ong, Mei-Kying; Zhang, Xuewu; Chai, Tsun-Thai","year":2024,"journal":"Foods (Basel, Switzerland), 13(18)","doi":"10.3390/foods13182945","pmid":"39335873","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08949","title":"Semaglutide Treatment in a Patient with Extreme Obesity and Massive Lymphedema: A Case Report.","authors":"Nguyen, Joanne Thanh-Tâm; Barbet-Massin, Marie-Amélie; Pupier, Emilie; Larroumet, Alice; Bosc, Laurène; Michelet, Marie; Monsaingeon-Henry, Maud; Gatta-Cherifi, Blandine","year":2024,"journal":"Obesity facts, 17(6), 641-645","doi":"10.1159/000540241","pmid":"39250902","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08950","title":"Reduction of prevalence of patients meeting the criteria for metabolic syndrome with tirzepatide: a post hoc analysis from the SURPASS Clinical Trial Program.","authors":"Nicholls, Stephen J; Tofé, Santiago; le Roux, Carel W; D'Alessio, David A; Wiese, Russell J; Pavo, Imre; Brown, Katelyn; Weerakkody, Govinda J; Zeytinoglu, Meltem; Romera, Irene C","year":2024,"journal":"Cardiovascular diabetology, 23(1), 63","doi":"10.1186/s12933-024-02147-9","pmid":"38341541","tags":["glp-1","metabolic-syndrome"],"studyType":"post-hoc-analysis","evidenceStrength":"strong","keyFinding":"Across the SURPASS 1–5 clinical trials, tirzepatide dramatically reduced the proportion of type 2 diabetes patients meeting criteria for metabolic syndrome. At baseline, 67–88% of patients across treatment groups had metabolic syndrome. After treatment, tirzepatide reduced this to 38–64%, compared to 64–82% with comparators (placebo, semaglutide 1 mg, insulin degludec, and insulin glargine).\n\nThe reductions were statistically significant at all tirzepatide doses versus all comparators (P<0.001). Every individual component of metabolic syndrome (insulin resistance, abdominal obesity, dyslipidemia, hypertension, hyperglycemia) improved more with tirzepatide. Greater weight loss corresponded to greater metabolic syndrome resolution. Background medication type and gender did not influence the results.","whyItMatters":"Metabolic syndrome isn't just one risk factor — it's a cluster of five that together dramatically increase heart disease, stroke, and diabetes complications. Showing that tirzepatide resolves metabolic syndrome at higher rates than semaglutide 1 mg, insulin glargine, and insulin degludec reinforces its position as potentially the most comprehensive metabolic drug available. Rather than treating individual risk factors with separate medications, tirzepatide addresses the entire syndrome simultaneously.","specificNumbers":"","methodology":"Post hoc analysis of the SURPASS 1–5 randomized clinical trial program. Metabolic syndrome was defined using the US National Cholesterol Education Program ATP III criteria (≥3 of 5 risk factors). Analysis was restricted to treatment-adherent patients (≥75% study drug compliance) using on-treatment data at each trial's primary endpoint. Logistic regression adjusted for baseline metabolic syndrome status was used to compare tirzepatide doses to all comparators.","limitations":"This is a post hoc analysis — the SURPASS trials were not originally designed to assess metabolic syndrome as a primary outcome. Post hoc analyses are hypothesis-generating rather than confirmatory. The comparator semaglutide dose was 1 mg (not the higher 2.4 mg dose used for weight management). Restricting to adherent patients (≥75% compliance) may overestimate real-world effectiveness. Long-term durability of metabolic syndrome resolution was not assessed."},{"rthcId":"RPEP-08951","title":"Molecular Mechanisms behind Obesity and Their Potential Exploitation in Current and Future Therapy.","authors":"Nicze, Michał; Dec, Adrianna; Borówka, Maciej; Krzyżak, Damian; Bołdys, Aleksandra; Bułdak, Łukasz; Okopień, Bogusław","year":2024,"journal":"International journal of molecular sciences, 25(15)","doi":"10.3390/ijms25158202","pmid":"39125772","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08952","title":"The Current and Promising Oral Delivery Methods for Protein- and Peptide-Based Drugs.","authors":"Nicze, Michał; Borówka, Maciej; Dec, Adrianna; Niemiec, Aleksandra; Bułdak, Łukasz; Okopień, Bogusław","year":2024,"journal":"International journal of molecular sciences, 25(2)","doi":"10.3390/ijms25020815","pmid":"38255888","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08953","title":"Stapled peptides as potential therapeutics for diabetes and other metabolic diseases.","authors":"Nielipińska, Dominika; Rubiak, Dominika; Pietrzyk-Brzezińska, Agnieszka J; Małolepsza, Joanna; Błażewska, Katarzyna M; Gendaszewska-Darmach, Edyta","year":2024,"journal":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 180, 117496","doi":"10.1016/j.biopha.2024.117496","pmid":"39362065","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Stapled peptides represent a significant advancement in peptide drug design for metabolic diseases. By stabilizing the α-helical conformation through chemical cross-links, these peptides gain enhanced stability against enzymatic degradation, improved cellular permeability, and stronger binding affinity for their targets.\n\nThe review describes how stapled peptides can function as agonists, antagonists, or dual-agonists by disrupting specific protein-protein interactions in metabolic pathways. Key targets include molecular pathways involved in glucose metabolism, insulin secretion, and food intake regulation. However, challenges remain in optimizing structural stability, controlling peptide helicity, managing isomer mixtures during synthesis, and minimizing potential side effects.","whyItMatters":"Peptide therapeutics are one of the fastest-growing drug classes, but their clinical potential is limited by poor stability and inability to reach intracellular targets. Stapling technology directly addresses these fundamental limitations. If stapled peptides can be reliably manufactured and prove safe in clinical trials, they could unlock an entirely new category of metabolic disease treatments targeting protein-protein interactions that are currently considered 'undruggable' by conventional peptide approaches.","specificNumbers":"","methodology":"This is a comprehensive narrative review that surveys the published literature on stapled peptide technology and its application to diabetes and metabolic diseases. The review covers stapling chemistry, structural considerations, target pathways, and development challenges.","limitations":"As a review article, this work synthesizes existing research rather than presenting new experimental data. Most stapled peptides for metabolic disease are still in preclinical stages, and the review acknowledges significant challenges including manufacturing complexity (isomer control), achieving consistent helicity, and limited clinical safety data. The jump from promising in vitro properties to effective in vivo therapeutics remains unproven for most metabolic stapled peptides."},{"rthcId":"RPEP-08954","title":"Large Libraries of Structurally Diverse Macrocycles Suitable for Membrane Permeation.","authors":"Nielsen, Alexander L; Bognar, Zsolt; Mothukuri, Ganesh K; Zarda, Anne; Schüttel, Mischa; Merz, Manuel L; Ji, Xinjian; Will, Edward J; Chinellato, Monica; Bartling, Christian R O; Strømgaard, Kristian; Cendron, Laura; Angelini, Alessandro; Heinis, Christian","year":2024,"journal":"Angewandte Chemie (International ed. in English), 63(26), e202400350","doi":"10.1002/anie.202400350","pmid":"38602024","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08955","title":"Machine-Learning-Guided Peptide Drug Discovery: Development of GLP-1 Receptor Agonists with Improved Drug Properties.","authors":"Nielsen, Jens Christian; Hjo Rringgaard, Claudia; Nygaard, Mads Mo Rup; Wester, Anita; Elster, Lisbeth; Porsgaard, Trine; Mikkelsen, Randi Bonke; Rasmussen, Silas; Madsen, Andreas Nygaard; Schlein, Morten; Vrang, Niels; Rigbolt, Kristoffer; Dalbo Ge, Louise S","year":2024,"journal":"Journal of medicinal chemistry, 67(14), 11814-11826","doi":"10.1021/acs.jmedchem.4c00417","pmid":"38977267","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08956","title":"Bioactive milk peptides: an updated comprehensive overview and database.","authors":"Nielsen, Søren Drud-Heydary; Liang, Ningjian; Rathish, Harith; Kim, Bum Jin; Lueangsakulthai, Jiraporn; Koh, Jeewon; Qu, Yunyao; Schulz, Hans-Jörg; Dallas, David C","year":2024,"journal":"Critical reviews in food science and nutrition, 64(31), 11510-11529","doi":"10.1080/10408398.2023.2240396","pmid":"37504497","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08957","title":"Improved Clinical Outcomes with the Combination Therapy of a Glucagon-like Peptide-1 Receptor Agonists and a Sodium-glucose Cotransporter-2 Inhibitor in Overweight/Obese People with Type 2 Diabetes: Real-world Evidence from the Indian Subcontinent.","authors":"Nigam, Anant","year":2024,"journal":"The Journal of the Association of Physicians of India, 72(9), 37-42","doi":"10.59556/japi.72.0644","pmid":"39291515","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08958","title":"Enhancing Tumor Targeted Therapy: The Role of iRGD Peptide in Advanced Drug Delivery Systems.","authors":"Nikitovic, Dragana; Kukovyakina, Ekaterina; Berdiaki, Aikaterini; Tzanakakis, Alexandros; Luss, Anna; Vlaskina, Elizaveta; Yagolovich, Anne; Tsatsakis, Aristides; Kuskov, Andrey","year":2024,"journal":"Cancers, 16(22)","doi":"10.3390/cancers16223768","pmid":"39594723","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08959","title":"Evaluation of GHK peptide-heparin interactions in multifunctional liposomal covering.","authors":"Nikolaeva, Viktoriia; Kamalov, Marat; Abdullin, Timur I; Salakhieva, Diana; Chasov, Vitaly; Rogov, Alexey; Zoughaib, Mohamed","year":2024,"journal":"Journal of liposome research, 34(1), 18-30","doi":"10.1080/08982104.2023.2206894","pmid":"37144381","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08960","title":"Exploring Erenumab's Efficacy and Safety for Migraine Prevention in Real-World Settings: A Systematic Review.","authors":"Nisar, Mah Rukh; Kotha, Rudrani; Saad-Omer, Sabaa I; Singh, Shivani; Olayinka, Oluwatoba T; Orelus, Jaslin; Yu, Ann Kashmer","year":2024,"journal":"Cureus, 16(7), e65571","doi":"10.7759/cureus.65571","pmid":"39192922","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08961","title":"Expression and localization of the neuropeptide Y-Y4 receptor in the chick spleen: mRNA upregulation by high ambient temperature.","authors":"Nishimura, Haruka; Elhussiny, Mohamed Z; Ouchi, Yoshimitsu; Haraguchi, Shogo; Itoh, Taichi Q; Gilbert, Elizabeth R; Cline, Mark A; Nishimura, Shotaro; Hosaka, Yoshinao Z; Takahashi, Eiki; Cockrem, John F; Bungo, Takashi; Chowdhury, Vishwajit S","year":2024,"journal":"Neuropeptides, 107, 102459","doi":"10.1016/j.npep.2024.102459","pmid":"39121580","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08962","title":"Adverse events in different administration routes of semaglutide: a pharmacovigilance study based on the FDA adverse event reporting system.","authors":"Niu, Kaibin; Fan, Maoxia; Gao, Wulin; Chen, Chen; Dai, Guohua","year":2024,"journal":"Frontiers in pharmacology, 15, 1414268","doi":"10.3389/fphar.2024.1414268","pmid":"38887555","tags":["semaglutide","GLP-1-agonists","drug-safety"],"studyType":"pharmacovigilance","evidenceStrength":"moderate","keyFinding":"Analysis of 22,287 adverse event reports from the FDA's FAERS database revealed distinct side effect profiles depending on whether semaglutide was given by injection or taken orally. Subcutaneous injection was more likely to cause endocrine-related adverse events, while oral semaglutide was more likely to trigger gastrointestinal side effects.\n\nNotably, oral administration also accelerated the onset of adverse reactions compared to injection. The study compared 16,346 subcutaneous injection reports against 2,496 oral administration reports from Q4 2017 through Q4 2023.","whyItMatters":"Millions of people now take semaglutide for diabetes or weight loss, and they often have a choice between injectable (Ozempic/Wegovy) and oral (Rybelsus) forms. Understanding that these routes carry different side effect profiles — not just different convenience levels — helps doctors and patients make more informed treatment decisions.","specificNumbers":"22,287 total adverse event reports · 16,346 subcutaneous reports · 2,496 oral reports · Q4 2017–Q4 2023","methodology":"Retrospective pharmacovigilance study analyzing real-world adverse event data from the FDA Adverse Event Reporting System (FAERS). Researchers used disproportionality analysis and reporting odds ratios (ROR) to compare adverse event signals between subcutaneous and oral semaglutide, along with stratified analysis and time-to-onset assessment.","limitations":"FAERS data is voluntarily reported and may be incomplete or biased toward more severe reactions. Reporting rates don't equal true incidence rates. The study cannot establish causation, only statistical associations. The oral semaglutide group was substantially smaller (2,496 vs. 16,346 reports), which may affect comparisons."},{"rthcId":"RPEP-08963","title":"The GLP-1 receptor agonist exenatide improves recovery from spinal cord injury by inducing macrophage polarization toward the M2 phenotype.","authors":"Noguchi, Toshihiro; Katoh, Hiroyuki; Nomura, Satoshi; Okada, Keiko; Watanabe, Masahiko","year":2024,"journal":"Frontiers in neuroscience, 18, 1342944","doi":"10.3389/fnins.2024.1342944","pmid":"38426018","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Rats receiving 10 μg exenatide subcutaneously immediately after spinal cord contusion injury showed significantly higher BBB locomotor scores (measuring hind limb motor function) from day 7 after injury onward compared to controls.\n\nThe mechanism involved macrophage polarization: exenatide increased expression of M2 (anti-inflammatory) markers and anti-inflammatory interleukins while decreasing M1 (pro-inflammatory) markers and inflammatory cytokines. Immunohistochemistry confirmed significantly more M2 macrophages in the exenatide group by day 3 after injury, while M1 macrophage numbers did not differ between groups — indicating the drug promoted anti-inflammatory immune cells rather than simply suppressing all immune activity.","whyItMatters":"Spinal cord injury has very limited treatment options, and the secondary inflammatory damage that follows the initial trauma is a major contributor to permanent disability. Finding that an already-approved drug like exenatide can shift the immune response from destructive to protective opens a realistic path toward clinical testing — bypassing years of drug development that would be needed for a novel compound.","specificNumbers":"","methodology":"Rat spinal cord contusion model was used. The exenatide group received a single subcutaneous injection of 10 μg exenatide immediately after injury; controls received PBS. Macrophage polarization was assessed by quantitative RT-PCR (gene expression of M1/M2 markers and cytokines) and immunohistochemical staining. Motor function recovery was measured using the BBB (Basso, Beattie, Bresnahan) locomotor rating scale.","limitations":"This was an animal study using a rat contusion model, which does not perfectly replicate human spinal cord injuries. Only a single dose of exenatide was tested, so optimal dosing and timing remain unknown. The number of animals per group was not specified in the abstract. Long-term outcomes beyond the observation period were not assessed, and the study did not examine whether repeated dosing might provide additional benefit."},{"rthcId":"RPEP-08964","title":"The GLP-1 Receptor Agonist Liraglutide Decreases Primary Bile Acids and Serotonin in the Colon Independently of Feeding in Mice.","authors":"Nonogaki, Katsunori; Kaji, Takao","year":2024,"journal":"International journal of molecular sciences, 25(14)","doi":"10.3390/ijms25147784","pmid":"39063026","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08965","title":"Liraglutide alleviated alpha-pyrrolidinovalerophenone (α-PVP) induced cognitive deficits in rats by modifying brain mitochondrial impairment.","authors":"Noruzi, Marzieh; Behmadi, Homayoon; Sabzevari, Omid; Foroumadi, Alireza; Ghahremani, Mohammad Hossein; Pourahmad, Jalal; Hassani, Shokoufeh; Baeeri, Maryam; Gholami, Mahdi; Ghahremanian, Amirhosein; Seyfi, Soheila; Taghizadeh, Ghorban; Sharifzadeh, Mohammad","year":2024,"journal":"European journal of pharmacology, 978, 176776","doi":"10.1016/j.ejphar.2024.176776","pmid":"38936451","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Liraglutide at both 47 and 94 μg/kg/day for 4 weeks ameliorated α-PVP-induced spatial learning and memory impairments in the Morris Water Maze. The cognitive recovery was accompanied by restoration of brain mitochondrial function: reduced reactive oxygen species (ROS) formation, restored mitochondrial membrane potential, decreased cytochrome c release, repaired mitochondrial outer membrane damage, reduced mitochondrial swelling, and normalized brain ADP/ATP ratios. These findings demonstrate that liraglutide's neuroprotective effects operate through mitochondrial rescue mechanisms.","whyItMatters":"Synthetic stimulant use is a growing global health crisis with limited treatment options for the cognitive damage they cause. This study suggests GLP-1 receptor agonists — already approved and widely available drugs — could be repurposed to treat substance-induced brain injury. The mitochondrial mechanism is particularly significant because mitochondrial dysfunction is a common pathway in many forms of neurotoxicity and neurodegeneration, meaning this approach could have broad applications.","specificNumbers":"","methodology":"Wistar rats (8 per group) received α-PVP (20 mg/kg/day intraperitoneally for 10 days) to induce cognitive deficits. Liraglutide was then administered at two doses (47 and 94 μg/kg/day IP) for 4 weeks. Spatial learning and memory were assessed using the Morris Water Maze 24 hours after treatment completion. Brain mitochondrial parameters were measured including ROS levels, membrane potential, cytochrome c release, outer membrane integrity, swelling, and ADP/ATP ratios.","limitations":"This is a rat study with 8 animals per group, which is a small sample. The α-PVP dose and administration route (intraperitoneal) may not perfectly model human recreational use patterns. Liraglutide was also given by injection rather than the subcutaneous route used clinically. The study did not examine long-term durability of cognitive improvements or potential mechanisms beyond mitochondrial function. Behavioral assessment was limited to spatial memory in the Morris Water Maze."},{"rthcId":"RPEP-08966","title":"Why are we still in need for novel anti-obesity medications?","authors":"Novikoff, Aaron; Grandl, Gerald; Liu, Xue; D Müller, Timo","year":2024,"journal":"The Lancet regional health. Europe, 47, 101098","doi":"10.1016/j.lanepe.2024.101098","pmid":"39726721","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08967","title":"Deciphering Antigen Processing Machinery (APM) as One of the Determinants for Responsiveness of Affected Patients towards Anticancer Immunotherapy.","authors":"Nurlaila, Ika","year":2024,"journal":"Asian Pacific journal of cancer prevention : APJCP, 25(12), 4457-4464","doi":"10.31557/APJCP.2024.25.12.4457","pmid":"39733439","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08968","title":"Suboptimal Weight Loss 13 Years After Roux-en-Y Gastric Bypass Is Associated with Blunted Appetite Response.","authors":"Nymo, Siren; Lundanes, Julianne; Eriksen, Kevin; Aukan, Marthe; Rehfeld, Jens Frederik; Holst, Jens Juul; Johnsen, Gjermund; Græslie, Hallvard; Kulseng, Bård; Sandvik, Jorunn; Martins, Catia","year":2024,"journal":"Obesity surgery, 34(2), 592-601","doi":"10.1007/s11695-023-07028-w","pmid":"38159146","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Patients with optimal weight loss (OWL) after RYGB had higher basal acylated ghrelin and greater post-meal GLP-1 responses (iAUC) compared to those with suboptimal weight loss (SWL) and controls. OWL patients also had lower post-meal ghrelin responses (iAUC) — meaning ghrelin dropped more after eating, signaling better satiety.\n\nBoth surgical groups showed elevated PYY and CCK post-meal responses compared to controls. Prospective food consumption ratings were lower in OWL than SWL. Total weight loss correlated positively with GLP-1 responses and negatively with hunger and desire-to-eat ratings, suggesting gut peptide signaling plays a key role in long-term weight maintenance after surgery.","whyItMatters":"Understanding why some patients maintain weight loss while others regain is critical for improving bariatric surgery outcomes. This study provides the longest follow-up comparison of gut hormone profiles after RYGB, suggesting that the appetite hormone system — particularly GLP-1 signaling — may determine long-term success. This could guide the development of targeted hormonal therapies for patients experiencing weight regain.","specificNumbers":"","methodology":"Cross-sectional comparison of 50 RYGB patients from the BAROBS study (25 SWL, 25 OWL) at 13+ years post-surgery, plus 25 non-surgical controls. Fasting and post-meal plasma concentrations of acylated ghrelin, GLP-1, PYY, and CCK were measured alongside subjective appetite ratings (hunger, fullness, desire to eat, prospective food consumption). Area under the curve analysis was used for postprandial responses.","limitations":"This was a cross-sectional observational study, so causality cannot be established — it's unclear whether the hormone differences caused the weight outcomes or resulted from them. Pre-surgical hormone levels were not available for comparison. The sample size (50 surgical patients) is relatively small. Dietary habits, physical activity, and psychological factors that influence weight were not comprehensively assessed."},{"rthcId":"RPEP-08969","title":"An Assessment of Sex and Gender Considerations in Migraine Calcitonin Gene-Related Peptide Clinical Trials.","authors":"O'Brien, Melissa S; Dawe, Jessica A J","year":2024,"journal":"The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques, 1-7","doi":"10.1017/cjn.2024.361","pmid":"39690430","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08970","title":"Interventions for Weight Management in Children and Adolescents: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.","authors":"O'Connor, Elizabeth A; Evans, Corinne V; Henninger, Michelle; Redmond, Nadia; Senger, Caitlyn A","year":2024,"journal":"JAMA, 332(3), 233-248","doi":"10.1001/jama.2024.6739","pmid":"38888913","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08971","title":"Novel Peptide-Drug Conjugates with Dual Anticancer Activity.","authors":"O'Flaherty, Siobhán; Luzina, Olga A; Dyrkheeva, Nadezhda S; Krier, Ysaline; Leprince, Jérôme; Zakharenko, Alexandra L; Pokrovsky, Mikhail A; Pokrovsky, Andrey G; Lavrik, Olga I; Salakhutdinov, Nariman F; Varbanov, Mihayl; Devocelle, Marc; Volcho, Konstantin P","year":2024,"journal":"International journal of molecular sciences, 25(22)","doi":"10.3390/ijms252212411","pmid":"39596476","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08972","title":"Effects of diets supplemented with bioactive peptides on nutrient digestibility, immune cell responsiveness, and fecal characteristics, microbiota, and metabolites of adult cats.","authors":"Oba, Patrícia M; De La Guardia Hidrogo, Vanessa M; Kelly, Janelle; Saunders-Blades, Jennifer; Steelman, Andrew J; Swanson, Kelly S","year":2024,"journal":"Journal of animal science, 102","doi":"10.1093/jas/skae104","pmid":"38587063","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08973","title":"Regulation of redox enzymes by nutraceuticals: a review of the roles of antioxidant polyphenols and peptides.","authors":"Obeme-Nmom, Joy I; Abioye, Raliat O; Reyes Flores, Samanta S; Udenigwe, Chibuike C","year":2024,"journal":"Food & function, 15(22), 10956-10980","doi":"10.1039/d4fo03549f","pmid":"39465304","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08974","title":"Microvascular Endothelial Function Assessed Using Peripheral Arterial Tonometry in Adolescents with Repaired Congenital Heart Disease.","authors":"Odanaka, Yutaka; Kishi, Kanta; Takigiku, Kiyohiro; Ashida, Atsuko; Ozaki, Noriyasu; Ashida, Akira","year":2024,"journal":"Pediatric cardiology, 45(8), 1804-1810","doi":"10.1007/s00246-023-03283-x","pmid":"37697168","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08975","title":"Efficacy and safety of oral semaglutide in older patients with type 2 diabetes: a retrospective observational study (the OTARU-SEMA study).","authors":"Oe, Yuki; Nomoto, Hiroshi; Cho, Kyu Yong; Yokozeki, Kei; Ono, Tsubasa; Miya, Aika; Kameda, Hiraku; Nakamura, Akinobu; Arimura, Yoshiaki; Atsumi, Tatsuya","year":2024,"journal":"BMC endocrine disorders, 24(1), 124","doi":"10.1186/s12902-024-01658-6","pmid":"39049060","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08976","title":"Wilms' tumor 1 -targeting cancer vaccine: Recent advancements and future perspectives.","authors":"Ogasawara, Masahiro","year":2024,"journal":"Human vaccines & immunotherapeutics, 20(1), 2296735","doi":"10.1080/21645515.2023.2296735","pmid":"38148629","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08977","title":"A meta-analysis of the incidence of acne vulgaris in patients treated with GLP-1 agonists.","authors":"Ogunremi, Oluwafunke O; Ismail, Sana F; Dhami, Ramneek K; Newton, Jazmin S; Kindle, Scott A; Kozmenko, Valeriy","year":2024,"journal":"International journal of women's dermatology, 10(2), e143","doi":"10.1097/JW9.0000000000000143","pmid":"38586157","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08978","title":"Enzyme-Linked Immunosorbent Assay for Antibodies Against the Tumor-Associated Antigen-Derived Cytotoxic T-Lymphocyte Epitope.","authors":"Oji, Yusuke","year":2024,"journal":"Methods in molecular biology (Clifton, N.J.), 2821, 217-223","doi":"10.1007/978-1-0716-3914-6_17","pmid":"38997492","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08979","title":"Restoring cellular copper homeostasis in Alzheimer disease: a novel peptide shuttle is internalized by an ATP-dependent endocytosis pathway involving Rab5- and Rab14-endosomes.","authors":"Okafor, Michael; Champomier, Olivia; Raibaut, Laurent; Ozkan, Sebahat; El Kholti, Naima; Ory, Stéphane; Chasserot-Golaz, Sylvette; Gasman, Stéphane; Hureau, Christelle; Faller, Peter; Vitale, Nicolas","year":2024,"journal":"Frontiers in molecular biosciences, 11, 1355963","doi":"10.3389/fmolb.2024.1355963","pmid":"38645276","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08980","title":"Inhibition of enhanced green fluorescent protein cytosolic delivery mediated by modified cell-penetrating peptide due to high overexpression of Caveolin-1.","authors":"Okuda, Akiko; Sugai, Keito; Okuda, Shujiro","year":2024,"journal":"Biochemical and biophysical research communications, 733, 150586","doi":"10.1016/j.bbrc.2024.150586","pmid":"39197200","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08981","title":"Blunted increase in plasma BNP during acute coronary syndrome attacks in obese patients.","authors":"Okuyama, Toraaki; Nagoshi, Tomohisa; Hiraki, Nana; Tanaka, Toshikazu D; Oi, Yuhei; Kimura, Haruka; Kashiwagi, Yusuke; Ogawa, Kazuo; Minai, Kosuke; Ogawa, Takayuki; Kawai, Makoto; Yoshimura, Michihiro","year":2024,"journal":"International journal of cardiology. Heart & vasculature, 54, 101508","doi":"10.1016/j.ijcha.2024.101508","pmid":"39314921","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08982","title":"Can Semaglutide offer hope for patients with obesity-related heart failure?","authors":"Olatunji, Gbolahan; Aderinto, Nicholas; Kokori, Emmanuel; Ogieuhi, Ikponmwosa Jude; Abraham, Israel Charles; Olanisa, Olawale; Nebuwa, Chikodili; Awoyinfa, Michael; Ajimotokan, Oluwafemi; Ajayi, Joan Oluwadamilola; Rao, Nitin Narayan; Temidayo, Ajayi Oluwatomisin; Napoleon, Tejiri; Samuel, Owolabi; Ezeano, Chimezirim","year":2024,"journal":"Current problems in cardiology, 49(9), 102697","doi":"10.1016/j.cpcardiol.2024.102697","pmid":"38871039","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08983","title":"FDG PET in a Patient on a GLP-1 Agonist/Insulin Secretagogue.","authors":"Oldan, Jorge D; Landman, Paula G; Schroeder, Jennifer A; Khandani, Amir H; Solnes, Lilja B; Lee, Carrie B; Rowe, Steven P","year":2024,"journal":"Clinical nuclear medicine, 49(9), e436-e438","doi":"10.1097/RLU.0000000000005318","pmid":"38914020","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A patient taking a GLP-1 receptor agonist/insulin secretagogue had a nondiagnostic FDG PET scan showing abnormal muscular and myocardial FDG uptake. The altered biodistribution was attributed to the drug's insulin-stimulating mechanism, which redirects glucose uptake to muscle and heart tissue, potentially masking tumor uptake and complicating scan interpretation.","whyItMatters":"With tens of millions of people now taking GLP-1 drugs like semaglutide for diabetes and weight loss, this is a growing practical concern for cancer imaging. If a PET scan can't distinguish tumors from medication-related uptake, cancers could be missed or patients could need repeat scans. Nuclear medicine physicians and oncologists need to know about this interaction.","specificNumbers":"","methodology":"This is a clinical case report describing a single patient's FDG PET scan findings in the context of GLP-1 receptor agonist use. The authors analyzed the scan findings, attributed the altered FDG biodistribution to the medication's effect on insulin secretion, and reviewed the clinical implications for nuclear medicine practice.","limitations":"This is a single case report, which is the lowest level of clinical evidence. The causal link between the GLP-1 drug and altered PET scan is presumptive, not definitively proven. Systematic studies with larger populations are needed to quantify how often this occurs and how significantly it affects scan diagnostic accuracy. The specific GLP-1 drug, dose, and timing relative to the scan are not detailed."},{"rthcId":"RPEP-08984","title":"Provocation of attacks to discover migraine signaling mechanisms and new drug targets: early history and future perspectives - a narrative review.","authors":"Olesen, Jes","year":2024,"journal":"The journal of headache and pain, 25(1), 105","doi":"10.1186/s10194-024-01796-1","pmid":"38902612","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08985","title":"Gut microbiota DPP4-like enzymes are increased in type-2 diabetes and contribute to incretin inactivation.","authors":"Olivares, Marta; Hernández-Calderón, Paula; Cárdenas-Brito, Sonia; Liébana-García, Rebeca; Sanz, Yolanda; Benítez-Páez, Alfonso","year":2024,"journal":"Genome biology, 25(1), 174","doi":"10.1186/s13059-024-03325-4","pmid":"38961511","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08986","title":"CGRP-targeted medication in chronic migraine - systematic review.","authors":"Oliveira, Renato; Gil-Gouveia, Raquel; Puledda, Francesca","year":2024,"journal":"The journal of headache and pain, 25(1), 51","doi":"10.1186/s10194-024-01753-y","pmid":"38575868","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Anti-CGRP monoclonal antibodies reduced monthly migraine days by 50% in 27.6-61.4% of chronic migraine patients across the reviewed studies. Conversion from chronic to episodic migraine occurred in 40.88% of cases. Between 29-88% of patients who were overusing acute medications successfully stopped. Obesity emerged as the main negative predictor of treatment response. Atogepant became the first gepant (oral CGRP receptor antagonist) to demonstrate significant reduction in monthly migraine days versus placebo. No single anti-CGRP monoclonal antibody showed clear superiority over others.","whyItMatters":"Chronic migraine affects millions of people and has limited treatment options, especially when medication overuse complicates the picture. This comprehensive review confirms that CGRP-targeting drugs represent a genuine breakthrough — they work, they're safe, and they help patients break the cycle of medication overuse. The finding about obesity as a predictor could help clinicians set realistic expectations.","specificNumbers":"","methodology":"The authors conducted a systematic review searching PubMed and Embase for randomized clinical trials and real-world studies on CGRP-targeting medications in chronic migraine patients. From 270 identified records, 19 studies met criteria for qualitative analysis. The review covered monoclonal antibodies (erenumab, fremanezumab, galcanezumab, eptinezumab) and gepants (atogepant), including combination therapy with onabotulinumtoxinA.","limitations":"The review included only 19 studies for qualitative analysis from 270 identified records, and a formal meta-analysis was not performed. Heterogeneity in study designs, endpoints, and patient populations across the included studies limits direct comparisons. Evidence for combination therapy with onabotulinumtoxinA was described as lacking strong evidence. Real-world studies may have selection bias compared to randomized trials."},{"rthcId":"RPEP-08987","title":"Dissection of an impact of VDR and RXRA on the genomic activity of 1,25(OH)2D3 in A431 squamous cell carcinoma.","authors":"Olszewska, Anna M; Nowak, Joanna I; Myszczynski, Kamil; Słominski, Andrzej; Żmijewski, Michał A","year":2024,"journal":"Molecular and cellular endocrinology, 582, 112124","doi":"10.1016/j.mce.2023.112124","pmid":"38123121","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08988","title":"Recent Advances and Therapeutic Benefits of Glucagon-Like Peptide-1 (GLP-1) Agonists in the Management of Type 2 Diabetes and Associated Metabolic Disorders.","authors":"Olukorode, John O; Orimoloye, Dolapo A; Nwachukwu, Nwachukwu O; Onwuzo, Chidera N; Oloyede, Praise O; Fayemi, Temiloluwa; Odunaike, Oluwatobi S; Ayobami-Ojo, Petra S; Divine, Nwachi; Alo, Demilade J; Alex, Chukwurah U","year":2024,"journal":"Cureus, 16(10), e72080","doi":"10.7759/cureus.72080","pmid":"39574978","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08989","title":"Comparison of Effects of Injectable Semaglutide and Dulaglutide on Oxidative Stress and Glucose Variability in Patients with Type 2 Diabetes Mellitus: A Prospective Preliminary Study.","authors":"Omachi, Takemasa; Ohara, Makoto; Fujikawa, Tomoki; Kohata, Yo; Sugita, Hiroe; Irie, Shunichiro; Terasaki, Michishige; Mori, Yusaku; Fukui, Tomoyasu; Yamagishi, Sho-Ichi","year":2024,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 15(1), 111-126","doi":"10.1007/s13300-023-01493-3","pmid":"37880502","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08990","title":"Improvement of comorbid anxiety and depression in patients with migraine treated with injectable preventive calcitonin gene-related peptide antagonists: Review of clinical evidence.","authors":"Omaer, Abubker; Albilali, Abdulrazaq; Bamogaddam, Reem; Almutairi, Fares; Alsaif, Raghad; Almohammadi, Osama; Alhifany, Abdullah A","year":2024,"journal":"Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society, 32(4), 101989","doi":"10.1016/j.jsps.2024.101989","pmid":"38405041","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08991","title":"Metabolic Abnormalities Following Tirzepatide Monotherapy in Japanese Patients with Type 2 Diabetes: A Phase 3 SURPASS J-mono Post Hoc Analysis.","authors":"Onishi, Yukiko; Oura, Tomonori; Takeuchi, Masakazu","year":2024,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 15(3), 649-661","doi":"10.1007/s13300-024-01534-5","pmid":"38310163","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08992","title":"Continuous Glucose Monitoring and the Effect of Liraglutide in Cardiac Surgery Patients: A Substudy of the Randomized Controlled GLOBE Trial.","authors":"Oosterom-Eijmael, Maartina J P; Hermanides, Jeroen; van Raalte, Daniël H; Kouw, Imre W K; DeVries, J Hans; Hulst, Abraham H","year":2024,"journal":"Journal of cardiothoracic and vascular anesthesia, 38(9), 1965-1971","doi":"10.1053/j.jvca.2024.06.015","pmid":"38977382","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08993","title":"Real-World Clinical Effectiveness of Liraglutide for Weight Management in Türkiye: Insights from the LIRA-TR Study.","authors":"Oral, Alihan; Küçük, Celalettin; Köse, Murat","year":2024,"journal":"Journal of clinical medicine, 13(20)","doi":"10.3390/jcm13206121","pmid":"39458071","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08994","title":"Calcitonin Gene-Related Peptide Monoclonal Antibodies: Key Lessons from Real-World Evidence.","authors":"Orlando, Bianca; Egeo, Gabriella; Aurilia, Cinzia; Fiorentini, Giulia; Barbanti, Piero","year":2024,"journal":"Brain sciences, 14(9)","doi":"10.3390/brainsci14090948","pmid":"39335442","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08995","title":"MicroRNA profiling in women with migraine: effects of CGRP-targeting treatment.","authors":"Ornello, Raffaele; Zelli, Veronica; Compagnoni, Chiara; Caponnetto, Valeria; De Matteis, Eleonora; Tiseo, Cindy; Tessitore, Alessandra; Sacco, Simona","year":2024,"journal":"The journal of headache and pain, 25(1), 80","doi":"10.1186/s10194-024-01787-2","pmid":"38755568","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08996","title":"Employment of mastoparan-like peptides to prevent Staphylococcus aureus associated with bovine mastitis.","authors":"Orozco, Raquel M Q; Oshiro, Karen G N; Pinto, Ingrid B; Buccini, Danieli F; Almeida, Claudiane V; Marin, Valentina Nieto; de Souza, Camila Maurmann; Macedo, Maria L R; Cardoso, Marlon H; Franco, Octávio L","year":2024,"journal":"Journal of bacteriology, 206(5), e0007124","doi":"10.1128/jb.00071-24","pmid":"38629875","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08997","title":"Semaglutide as a possible therapy for healthy aging: Targeting the hallmarks of aging.","authors":"Ortiz, Gabriela Ueta; de Freitas, Ellen Cristini","year":2024,"journal":"Ageing research reviews, 102, 102582","doi":"10.1016/j.arr.2024.102582","pmid":"39547367","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-08998","title":"Gastrointestinal Safety Assessment of GLP-1 Receptor Agonists in the US: A Real-World Adverse Events Analysis from the FAERS Database.","authors":"Osei, Samuel Prince; Akomaning, Edwin; Florut, Teodora Francesca; Sodhi, Mohit; Lacy, Brian E; Aldhaleei, Wafa A; Bhagavathula, Akshaya Srikanth","year":2024,"journal":"Diagnostics (Basel, Switzerland), 14(24)","doi":"10.3390/diagnostics14242829","pmid":"39767190","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"From 2007-2023, 187,757 adverse events were reported with GLP-1 RAs in the US, including 16,568 GI-related events. Semaglutide was significantly associated with nausea, vomiting, and delayed gastric emptying. Exenatide was associated with pancreatitis and a significantly elevated death risk (ROR: 4.50).\n\nDulaglutide and liraglutide were associated with fewer significant GI adverse events compared to semaglutide and exenatide. Semaglutide had the broadest range of notable GI adverse effects among all GLP-1 RAs analyzed.","whyItMatters":"With millions of people now taking GLP-1 drugs, understanding the comparative GI safety profile of different drugs in this class is crucial for prescribing decisions. This real-world data from nearly 188,000 adverse events provides a practical guide: patients prone to nausea may do better on dulaglutide or liraglutide than semaglutide, and the exenatide pancreatitis signal reinforces the need for monitoring.","specificNumbers":"","methodology":"Retrospective pharmacovigilance study using the US FDA FAERS database from 2007-2023. The researchers collected demographic, treatment indication, and adverse event data for all GLP-1 RA medications. Analysis used reporting odds ratios, proportional reporting ratios, Bayesian confidence propagation neural networks, and multivariate logistic regression to identify significant safety signals.","limitations":"FAERS data relies on voluntary reporting, which introduces reporting bias — more popular drugs (like semaglutide) may have more reports simply due to higher usage. The data cannot establish causation, only statistical associations. Reporting rates may not reflect true incidence rates. The exenatide death signal needs careful interpretation given that it was an earlier drug used in a potentially sicker population. Confounders like concomitant medications and comorbidities are difficult to control in FAERS analyses."},{"rthcId":"RPEP-08999","title":"Long-Term Effects of Incretin-Based Drugs on Glycemic Control in Permanent Neonatal Diabetes.","authors":"Oshiro, Ayaka; Aotani, Ryoichiro; Sakamoto, Wakako; Kitazono, Takanari; Ohkuma, Toshiaki","year":2024,"journal":"JCEM case reports, 2(11), luae188","doi":"10.1210/jcemcr/luae188","pmid":"39430732","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Starting sitagliptin (DPP-4 inhibitor, 50 mg/day) enabled complete insulin discontinuation (from 47 U/day) and reduced HbA1c by 4.8% in a patient with permanent neonatal diabetes on high-dose glibenclamide (0.6 mg/kg/day). Doubling the sitagliptin dose and subsequently switching to semaglutide (GLP-1 receptor agonist, 0.25 then 0.5 mg/week) produced further HbA1c improvements with graded increases in endogenous insulin secretion.\n\nGlibenclamide was safely downtitrated from 0.6 to 0.4 mg/kg/day without hypoglycemia. Continuous glucose monitoring showed improvements in both intra- and inter-day glucose variability, indicating more stable blood sugar control throughout the day.","whyItMatters":"Permanent neonatal diabetes is typically managed with insulin and sulfonylureas, but many patients struggle to achieve good glycemic control. This case demonstrates that incretin-based therapies — which work by enhancing the body's natural peptide hormone signaling — can dramatically improve outcomes even in a genetic form of diabetes where insulin secretion is inherently impaired. The 4.8% HbA1c reduction is clinically extraordinary and suggests that incretin pathways retain therapeutic potential even when β-cell function is genetically compromised.","specificNumbers":"","methodology":"This is a single case report of a 24-year-old woman with permanent neonatal diabetes mellitus. Treatment changes were made sequentially: addition of sitagliptin to existing insulin and glibenclamide, then sitagliptin dose escalation, then switch to semaglutide. Glycemic control was monitored through HbA1c, continuous glucose monitoring (for variability), and assessment of endogenous insulin secretion markers. Hypoglycemia episodes were tracked throughout.","limitations":"This is a single case report (n=1), the weakest level of clinical evidence. The dramatic response may not be generalizable to other PNDM patients, as the specific genetic mutation was not detailed in the abstract and different mutations may respond differently. The mechanism behind the enhanced insulin secretion with incretin drugs in this genetic context is not fully explained. Follow-up duration was not specified, so long-term durability of the response is unknown."},{"rthcId":"RPEP-09000","title":"Glycaemic control, body weight, and safety of tirzepatide versus dulaglutide by baseline glycated haemoglobin level in Japanese patients with type 2 diabetes: A subgroup analysis of the SURPASS J-mono study.","authors":"Osonoi, Takeshi; Oura, Tomonori; Hirase, Tetsuaki","year":2024,"journal":"Diabetes, obesity & metabolism, 26(1), 126-134","doi":"10.1111/dom.15296","pmid":"37794628","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09001","title":"Peptide derived from plant defensins: A promising 68Ga radiolabelled agent for diagnostic of infection foci in PET.","authors":"Osorio, Jessica; Rosas, Roberto Castro; Vega, Mariana Barraco; Reyes, Ana Laura; Paolino, Andrea; Menéndez, Florencia; Vega-Teijido, Mauricio; Savio, Eduardo; Giglio, Javier; Cecchetto, Gianna; Terán, Mariella","year":2024,"journal":"Chemical biology & drug design, 104(1), e14578","doi":"10.1111/cbdd.14578","pmid":"39044291","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09002","title":"A secreted bacterial protein protects bacteria from cationic antimicrobial peptides by entrapment in phase-separated droplets.","authors":"Ostan, Nicholas K H; Cole, Gregory B; Wang, Flora Zhiqi; Reichheld, Sean E; Moore, Gaelen; Pan, Chuxi; Yu, Ronghua; Lai, Christine Chieh-Lin; Sharpe, Simon; Lee, Hyun O; Schryvers, Anthony B; Moraes, Trevor F","year":2024,"journal":"PNAS nexus, 3(4), pgae139","doi":"10.1093/pnasnexus/pgae139","pmid":"38633880","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09003","title":"Tirzepatide 5, 10 and 15 mg versus injectable semaglutide 0.5 mg for the treatment of type 2 diabetes: An adjusted indirect treatment comparison.","authors":"Osumili, Beatrice; Fan, Ludi; Paik, Jim S; Pantalone, Kevin M; Ranta, Kari; Sapin, Hélène; Tofé, Santiago","year":2024,"journal":"Diabetes research and clinical practice, 212, 111717","doi":"10.1016/j.diabres.2024.111717","pmid":"38777128","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09004","title":"Improving glycemic control: transitioning from dulaglutide to tirzepatide in patients with type 2 diabetes undergoing hemodialysis.","authors":"Otsuka, Emiko; Kitamura, Mineaki; Funakoshi, Satoshi; Mukae, Hiroshi; Nishino, Tomoya","year":2024,"journal":"Frontiers in pharmacology, 15, 1362242","doi":"10.3389/fphar.2024.1362242","pmid":"38873429","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Switching from dulaglutide (a single GLP-1 agonist) to tirzepatide (a dual GIP/GLP-1 agonist) in 14 hemodialysis patients with type 2 diabetes significantly improved blood sugar control. Time in range increased from 42.7% to 50.8% (p=0.02), time above range dropped from 48.4% to 37.8% (p=0.02), and mean glucose fell from 156.6 to 137.4 mg/dL (p=0.006). Critically, hypoglycemia did not increase — time below range was statistically unchanged at 11.3% vs 8.9% (p=0.75). Side effects were mild: 21.4% had dyspepsia and 7.1% had nausea, with no serious adverse events.","whyItMatters":"Hemodialysis patients with diabetes are among the hardest to manage — their kidney failure alters drug metabolism, and blood sugar swings during dialysis create dangerous highs and lows. Most incretin drug trials exclude these patients. This study provides rare real-world evidence that tirzepatide can safely improve glycemic control in this underserved population.","specificNumbers":"TIR: 42.7%→50.8% (p=0.02); TAR: 48.4%→37.8% (p=0.02); mean glucose: 156.6→137.4 mg/dL (p=0.006); TBR: 11.3% vs 8.9% (p=0.75)","methodology":"Single-center retrospective study using continuous glucose monitoring (CGM) in 14 type 2 diabetes patients undergoing hemodialysis who were switched from dulaglutide to tirzepatide. Glucose metrics were compared before and after the transition.","limitations":"Very small sample of only 14 patients at a single center. Retrospective design limits the ability to control for confounders. No long-term follow-up data. The study lacks a control group that stayed on dulaglutide."},{"rthcId":"RPEP-09005","title":"Analysis of tirzepatide in the US FDA adverse event reporting system (FAERS): a focus on overall patient population and sex-specific subgroups.","authors":"Ou, Yingyong; Cui, Zhiwei; Lou, Siyu; Zhu, Chengyu; Chen, Junyou; Zhou, Linmei; Zhao, Ruizhen; Wang, Li; Zou, Fan","year":2024,"journal":"Frontiers in pharmacology, 15, 1463657","doi":"10.3389/fphar.2024.1463657","pmid":"39568578","tags":["glp-1"],"studyType":"pharmacovigilance","evidenceStrength":"moderate","keyFinding":"Analysis of 37,827 adverse event reports for tirzepatide in the FDA's FAERS database identified 100 statistically significant adverse event signals. The most commonly reported events were incorrect dose administered, injection site pain, off-label use, nausea, and injection site hemorrhage. An unexpected safety signal — starvation ketoacidosis — was identified.\n\nNotably, side effects differed between sexes: men primarily reported gastrointestinal disorders, while women more commonly reported general disorders and injection site reactions. The median time to onset for adverse events was 23 days after starting tirzepatide.","whyItMatters":"With millions of people now using tirzepatide (Mounjaro/Zepbound), real-world safety data from spontaneous reporting systems like FAERS captures adverse events that clinical trials — which are controlled and time-limited — may miss. The identification of starvation ketoacidosis as an unexpected signal is clinically important, and the sex-based differences in side effect patterns could inform personalized monitoring strategies.","specificNumbers":"37,827 ADE reports · 100 significant signals · Top 5: incorrect dose, injection site pain, off-label use, nausea, injection site hemorrhage · Median onset: 23 days · Starvation ketoacidosis: unexpected signal · Sex-specific patterns identified","methodology":"Pharmacovigilance study mining the FDA Adverse Event Reporting System (FAERS) database from Q2 2022 through Q1 2024. Disproportionality analyses used four validated algorithms (ROR, PRR, BCPNN, MGPS) to identify statistically significant adverse event signals. Only events flagged by all four algorithms were considered significant. Sex-specific subgroup analyses were performed.","limitations":"FAERS is a spontaneous reporting system subject to reporting bias — serious events are overreported while mild events are underreported. Reports don't prove causation; many patients have comorbidities and take other medications. Off-label use as a 'top 5 event' reflects reporting patterns rather than a true adverse event. The database cannot calculate true incidence rates (no denominator of total users). Duplicate reports may inflate numbers."},{"rthcId":"RPEP-09006","title":"Estimated glomerular filtration rate slope and risk of primary and secondary major adverse cardiovascular events and heart failure hospitalization in people with type 2 diabetes: An analysis of the EXSCEL trial.","authors":"Oulhaj, Abderrahim; Aziz, Faisal; Suliman, Abubaker; Eller, Kathrin; Bentoumi, Rachid; Buse, John B; Al Mahmeed, Wael; von Lewinski, Dirk; Coleman, Ruth L; Holman, Rury R; Sourij, Harald","year":2024,"journal":"Diabetes, obesity & metabolism, 26(10), 4602-4612","doi":"10.1111/dom.15817","pmid":"39086032","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09007","title":"Multimodal ultrasound imaging of a rat model with ischemic heart failure and its relationship to histopathology.","authors":"Ouyang, Qiufang; Xu, Rong; Lin, Qing; Yan, Jinxian; Zhang, Luting; Zhao, Hongjia","year":2024,"journal":"American journal of translational research, 16(9), 4589-4600","doi":"10.62347/FIWE8677","pmid":"39398608","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09008","title":"Pituitary Disorders.","authors":"Owolabi, Mark; Malone, Michael; Merritt, Andrew","year":2024,"journal":"Primary care, 51(3), 467-481","doi":"10.1016/j.pop.2024.04.004","pmid":"39067972","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09009","title":"Naturally occurring low sociality in female rhesus monkeys: A tractable model for autism or not?","authors":"Oztan, Ozge; Del Rosso, Laura A; Simmons, Sierra M; Nguyen, Duyen K K; Talbot, Catherine F; Capitanio, John P; Garner, Joseph P; Parker, Karen J","year":2024,"journal":"Molecular autism, 15(1), 8","doi":"10.1186/s13229-024-00588-3","pmid":"38291493","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09010","title":"Neuroprotection by Cerebrolysin and Citicoline Through the Upregulation of Brain-Derived Neurotrophic Factor (BDNF) Expression in the Affected Neural Cells: A Preliminary Clue Obtained Through an In Vitro Study.","authors":"P, Anandan; Rengarajan, Santhanam; Venkatachalam, Sankar; Pattabi, Sasikumar; Jones, Sumathi; K, Prabhu; Krishna, Vani; Prasanth, Krishna","year":2024,"journal":"Cureus, 16(2), e54665","doi":"10.7759/cureus.54665","pmid":"38524067","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09011","title":"Weight maintenance on cost-effective antiobesity medications after 1 year of GLP-1 receptor agonist therapy: a real-world study.","authors":"Paddu, Nina U; Lawrence, Brianna; Wong, Sydnee; Poon, Sabrina J; Srivastava, Gitanjali","year":2024,"journal":"Obesity (Silver Spring, Md.), 32(12), 2255-2263","doi":"10.1002/oby.24177","pmid":"39558626","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09012","title":"Neuronal substance P drives metastasis through an extracellular RNA-TLR7 axis.","authors":"Padmanaban, Veena; Keller, Isabel; Seltzer, Ethan S; Ostendorf, Benjamin N; Kerner, Zachary; Tavazoie, Sohail F","year":2024,"journal":"Nature, 633(8028), 207-215","doi":"10.1038/s41586-024-07767-5","pmid":"39112700","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09013","title":"Neuropeptide Y receptor activation preserves inner retinal integrity through PI3K/Akt signaling in a glaucoma mouse model.","authors":"Palanivel, Viswanthram; Gupta, Vivek; Chitranshi, Nitin; Tietz, Ole; Vander Wall, Roshana; Blades, Reuben; Maha Thananthirige, Kanishka Pushpitha; Salkar, Akanksha; Shen, Chao; Mirzaei, Mehdi; Gupta, Veer; Graham, Stuart L; Basavarajappa, Devaraj","year":2024,"journal":"PNAS nexus, 3(8), pgae299","doi":"10.1093/pnasnexus/pgae299","pmid":"39114576","tags":["neuropeptide-y"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Neuropeptide Y (NPY) treatment preserved both structural and functional integrity of the inner retina in a mouse model of glaucoma with elevated intraocular pressure. NPY mitigated axonal damage and optic nerve degeneration, reduced inflammatory glial cell activation (decreased GFAP and Iba-1 expression), and restored endogenous NPY and receptor levels (NPY-Y1R and NPY-Y4R) that were depleted under high pressure conditions.\n\nMolecular analysis revealed NPY works through MAPK and PI3K/Akt signaling pathways to achieve its protective effects.","whyItMatters":"Glaucoma is a leading cause of irreversible blindness, and current treatments focus on lowering eye pressure without directly protecting the nerve cells that die. This study shows a natural brain peptide — neuropeptide Y — can directly protect retinal ganglion cells from pressure-induced damage through multiple mechanisms: reducing inflammation, preventing cell death, and restoring healthy signaling. It opens a potential new therapeutic avenue that targets the neurodegeneration itself, not just the pressure.","specificNumbers":"36-amino-acid peptide · NPY-Y1R and NPY-Y4R receptors restored · GFAP and Iba-1 reduced · MAPK and PI3K/Akt pathways activated","methodology":"Mouse glaucoma model using intracameral microbead injections to elevate intraocular pressure, combined with intravitreal injection of NPY peptide. Researchers assessed retinal structure and function, optic nerve integrity, inflammatory markers (GFAP, Iba-1), endogenous NPY and receptor expression, and molecular signaling pathways (MAPK, PI3K/Akt).","limitations":"This is a mouse model study — results may not directly translate to human glaucoma. Intravitreal injection is invasive and would need practical delivery solutions for clinical use. The study does not report long-term outcomes or whether repeated dosing would be needed. Specific quantitative outcomes (e.g., percentage of ganglion cell preservation) are not detailed in the abstract."},{"rthcId":"RPEP-09014","title":"Lymph-node-targeted, mKRAS-specific amphiphile vaccine in pancreatic and colorectal cancer: the phase 1 AMPLIFY-201 trial.","authors":"Palmer, Chrisann D; Rappaport, Aaron R; Davis, Megan J; Hart, Michael G; Scallan, Ciaran D; Hong, Sook-Ja; Gitlin, Leonid; Kraemer, Lauren D; Kounlavouth, Stephanie; Yang, Amy; Smith, Lindsay; Schenkel, Jason M; Keenan, Brendan P; Kleponis, James; Vonderheide, Robert H; Wainberg, Zev A; Luke, Jason J; Piening, Brian D; Claman, Dana; Du, Kelan; Brockstedt, Dirk G; Tversky, Erica; Drakes, Darren J; Elson, Kyle; Mick, Eric; Pettit Kneller, Emily L; Addario, Bruce; Klempner, Samuel J","year":2024,"journal":"Nature medicine, 30(2), 531-542","doi":"10.1038/s41591-023-02760-3","pmid":"38195752","tags":["cancer-research","peptide-engineering"],"studyType":"human-phase-1","evidenceStrength":"moderate","keyFinding":"ELI-002 2P amphiphile vaccine targeting 7 mKRAS mutations induced T cell responses in 84% of 25 patients with pancreatic/colorectal cancer and reduced ctDNA in 24%. Well-tolerated with no dose-limiting toxicities.","whyItMatters":"First human trial showing shared KRAS mutations can be targeted with vaccination, opening a nonpersonalized immunotherapy approach for the three deadliest cancers.","specificNumbers":"25 patients; 84% T cell response rate; 24% ctDNA reduction; 7 KRAS mutations targeted","methodology":"Phase 1, open-label trial in 25 patients with mKRAS+ pancreatic or colorectal cancer with minimal residual disease. SC injection of amphiphile-linked mKRAS peptides + CpG adjuvant.","limitations":"Small phase 1, no control arm, ctDNA is a surrogate marker."},{"rthcId":"RPEP-09015","title":"Efficacy and safety of tirzepatide, GLP-1 receptor agonists, and other weight loss drugs in overweight and obesity: a network meta-analysis.","authors":"Pan, Xin-Hui; Tan, Bryan; Chin, Yip Han; Lee, Ethan Cheng Zhe; Kong, Gwyneth; Chong, Bryan; Kueh, Martin; Khoo, Chin Meng; Mehta, Anurag; Majety, Priyanka; Grandhi, Gowtham R; Dimitriadis, Georgios K; Foo, Roger; Chew, Nicholas W S; Le Roux, Carel W; Mamas, Mamas A; Chan, Mark Y","year":2024,"journal":"Obesity (Silver Spring, Md.), 32(5), 840-856","doi":"10.1002/oby.24002","pmid":"38413012","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09016","title":"Harnessing Peptide-Based Hydrogels for Enhanced Cartilage Tissue Engineering.","authors":"Pande, Shreya; Pati, Falguni; Chakraborty, Priyadarshi","year":2024,"journal":"ACS applied bio materials, 7(9), 5885-5905","doi":"10.1021/acsabm.4c00879","pmid":"39159490","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09017","title":"Estimating the lives that could be saved by expanded access to weight-loss drugs.","authors":"Pandey, Abhishek; Ye, Yang; Wells, Chad R; Singer, Burton H; Galvani, Alison P","year":2024,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 121(43), e2412872121","doi":"10.1073/pnas.2412872121","pmid":"39405358","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09018","title":"Liraglutide innovations: a comprehensive review of patents (2014-2024).","authors":"Pandey, Ajay; Goyal, Amit Kumar","year":2024,"journal":"Pharmaceutical patent analyst, 13(1-3), 73-89","doi":"10.1080/20468954.2024.2366693","pmid":"39316579","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09019","title":"Enhanced Antimicrobial Peptide Response Following Bacillus Calmette-Guerin Vaccination in Elderly Individuals.","authors":"Pandiarajan, Arul Nancy; Kumar, Nathella Pavan; Rajamanickam, Anuradha; Bhavani, Perumal Kannabiran; Jeyadeepa, Bharathi; Selvaraj, Nandhini; Asokan, Dinesh; Tripathy, Srikanth; Padmapriyadarsini, Chandrasekharan; Babu, Subash","year":2024,"journal":"Vaccines, 12(9)","doi":"10.3390/vaccines12091065","pmid":"39340094","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09020","title":"From Glucose to Neuroprotection: Exploring Antidiabetic Medications as a Novel Approach to Alzheimer's Disease Treatment.","authors":"Pandiyan, Chandaraa Kumar; Manivannan, Arjun Gokulan; Jaishankar, Narayanan; Vellapandian, Chitra","year":2024,"journal":"Cureus, 16(10), e70710","doi":"10.7759/cureus.70710","pmid":"39493064","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09021","title":"Restoration of the Lost Human Beta Defensin-1 Protein in Cancer as a Strategy to Improve the Efficacy of Chemotherapy.","authors":"Pandurangi, Raghu; Sekar, Thillai; Paulmurugan, Ramasamy","year":2024,"journal":"Journal of medicinal chemistry, 67(16), 14200-14209","doi":"10.1021/acs.jmedchem.4c01040","pmid":"39137365","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09022","title":"Improving combination cancer immunotherapy by manipulating dual immunomodulatory signals with enzyme-triggered, cell-penetrating peptide-mediated biomodulators.","authors":"Pang, Guibin; Chen, Piao; Cao, Xuewei; Yu, Huan; Zhang, Leshuai W; Zhao, Jian; Wang, Fu-Jun","year":2024,"journal":"Biomaterials science, 12(3), 776-789","doi":"10.1039/d3bm01605f","pmid":"38167881","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The researchers created chimeric protein biomodulators using enzyme-triggered, cell-penetrating peptides to deliver GADD34-derived motifs into tumor cells. These motifs inhibit protein phosphatase 1 (PP1), which enhances calreticulin exposure on tumor surfaces — an \"eat me\" signal for immune cells.\n\nThe platform was modular, allowing combination with either:\n- Cytotoxic BLF1 to provide additional \"eat me\" signaling through phosphatidylserine exposure\n- Immunomodulatory designed ankyrin repeat proteins to block PD-L1 (\"don't find me\" signaling)\n\nThese bifunctional biomodulators induced macrophage phagocytosis, dendritic cell maturation, and CD8+ T cell activation, resulting in substantial tumor growth inhibition.","whyItMatters":"Cancer immunotherapy often fails because tumors create an immunosuppressive environment. This modular peptide platform addresses multiple immune evasion mechanisms simultaneously — making tumors visible to the immune system while disabling their defenses — which could overcome resistance to current single-target immunotherapies.","specificNumbers":"","methodology":"The researchers designed chimeric protein scaffolds incorporating cell-penetrating peptide sequences, PP1-disrupting GADD34 motifs, and secondary immunomodulatory payloads (BLF1 or anti-PD-L1 ankyrin proteins). They tested cellular uptake, calreticulin exposure, phosphatidylserine display, immune cell activation (macrophage phagocytosis, dendritic cell maturation, CD8+ T cell activation), and tumor growth inhibition in cell culture and tumor models.","limitations":"The abstract does not specify whether tumor growth inhibition was demonstrated in vitro only or also in animal models. The modular platform's complexity could present manufacturing and stability challenges for clinical translation. Long-term safety, off-target effects, and performance against diverse tumor types remain to be evaluated."},{"rthcId":"RPEP-09023","title":"Bioactive Properties of Enzymatic Gelatin Hydrolysates Based on In Silico, In Vitro, and In Vivo Studies.","authors":"Panjaitan, Fenny Crista A; Shie, Sin-Ting; Park, Sung Hoon; Sevi, Tesalonika; Ko, Wen-Ling; Aluko, Rotimi E; Chang, Yu-Wei","year":2024,"journal":"Molecules (Basel, Switzerland), 29(18)","doi":"10.3390/molecules29184402","pmid":"39339395","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09024","title":"Amylin analogs for the treatment of obesity without diabetes: present and future.","authors":"Panou, Theodoros; Gouveri, Evanthia; Popovic, Djordje S; Papanas, Nikolaos","year":2024,"journal":"Expert review of clinical pharmacology, 1-9","doi":"10.1080/17512433.2024.2409403","pmid":"39317404","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09025","title":"Changes in body weight and composition, metabolic parameters, and quality of life in patients with type 2 diabetes treated with subcutaneous semaglutide in real-world clinical practice.","authors":"Pantanetti, Paola; Cangelosi, Giovanni; Alberti, Sara; Di Marco, Sandra; Michetti, Grazia; Cerasoli, Gianluca; Di Giacinti, Marco; Coacci, Silvia; Francucci, Nadia; Petrelli, Fabio; Ambrosio, Giuseppe; Grinta, Roberto","year":2024,"journal":"Frontiers in endocrinology, 15, 1394506","doi":"10.3389/fendo.2024.1394506","pmid":"39015186","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09026","title":"Oral Semaglutide in Type 2 Diabetes: Clinical-Metabolic Outcomes and Quality of Life in Real-World Practice.","authors":"Pantanetti, Paola; Ronconi, Vanessa; Sguanci, Marco; Palomares, Sara Morales; Mancin, Stefano; Tartaglia, Francesco Carlo; Cangelosi, Giovanni; Petrelli, Fabio","year":2024,"journal":"Journal of clinical medicine, 13(16)","doi":"10.3390/jcm13164752","pmid":"39200893","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"After 6 months of oral semaglutide (14 mg/day) in 61 T2D patients: HbA1c decreased by 1.24% (SD 1.33, p significant), fasting plasma glucose decreased significantly, body composition and anthropometric parameters improved significantly, blood pressure decreased, cardiovascular risk factors improved, Diabetes Treatment Satisfaction Questionnaire (DTSQ) scores improved significantly, and SF-36 quality of life scores improved significantly. Average diabetes duration was 4.67 ± 3.93 years.","whyItMatters":"Treatment satisfaction and quality of life are critical but often overlooked in diabetes care. Many patients resist injectable medications, so an oral GLP-1 option that not only improves metabolic markers but also makes patients feel better about their treatment could improve long-term adherence. This is one of the few real-world studies capturing both clinical outcomes and patient-reported outcomes for oral semaglutide.","specificNumbers":"","methodology":"Prospective observational study with 6-month follow-up. Sixty-one subjects with type 2 diabetes were enrolled. Clinical parameters collected at baseline (T0) and 6 months (T1) included HbA1c, fasting plasma glucose, anthropometric measurements, blood pressure, cardiovascular risk factors, DTSQ (treatment satisfaction), and SF-36 (health-related quality of life).","limitations":"Small sample size (61 patients) at a single site limits generalizability. No control group means improvements could be partly attributed to concurrent lifestyle changes, medication adjustments, or the Hawthorne effect. The 6-month follow-up is relatively short. The abstract mentions significant p-values but formatting errors prevent seeing specific values for several outcomes. Selection bias may favor motivated patients. The DTSQ and SF-36 improvements could reflect novelty of the medication rather than sustained satisfaction."},{"rthcId":"RPEP-09027","title":"The Influence of GLP1 on Body Weight and Glycemic Management in Patients with Diabetes-A Scientometric Investigation and Visualization Study.","authors":"Pantea, Ileana; Repanovici, Angela; Andreescu, Oana","year":2024,"journal":"Medicina (Kaunas, Lithuania), 60(11)","doi":"10.3390/medicina60111761","pmid":"39596946","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09028","title":"Discovery of Novel Thanatin-like Antimicrobial Peptides from Bean Bug Riptortus pedestris.","authors":"Panteleev, Pavel V; Teplovodskaya, Julia S; Utkina, Anastasia D; Smolina, Anastasia A; Kruglikov, Roman N; Safronova, Victoria N; Bolosov, Ilia A; Korobova, Olga V; Borzilov, Alexander I; Ovchinnikova, Tatiana V","year":2024,"journal":"Pharmaceutics, 16(11)","doi":"10.3390/pharmaceutics16111453","pmid":"39598576","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Three novel thanatin-like β-hairpin antimicrobial peptides (Rip-2, Rip-3, Rip-4) were discovered in the bean bug Riptortus pedestris through transcriptome mining. Homologs are widely distributed across the insect infraorder Pentatomomorpha.\n\nRip-2 shared structural similarity with thanatin and targeted the LptA protein, showing higher activity than thanatin against key Gram-negative ESKAPE pathogens. It demonstrated significant efficacy in a lethal mouse septicemia model caused by E. coli at daily doses >5 mg/kg. Rip-3 and Rip-4 had a different mechanism — membrane damage rather than LptA targeting. They showed strong selectivity against Bacillus and Mycobacterium species, did not induce bacterial resistance, and had different antimicrobial spectra.","whyItMatters":"Antimicrobial resistance is projected to cause millions of deaths annually if new antibiotics aren't developed. Insect antimicrobial peptides represent a largely untapped source of novel antibiotic candidates. The discovery that these bug-derived peptides can kill drug-resistant ESKAPE pathogens and save mice from lethal infections — while using mechanisms that don't easily trigger resistance — makes them promising templates for next-generation antibiotics.","specificNumbers":"","methodology":"Researchers used transcriptome mining to identify novel antimicrobial peptide genes in the bean bug Riptortus pedestris. The three identified peptides were expressed using a bacterial expression system. Antimicrobial activity was tested in vitro against various bacterial strains, and Rip-2 was further evaluated in vivo using a lethal E. coli septicemia model in mice. Mechanisms of action were characterized including LptA targeting and membrane damage assays.","limitations":"The study is preclinical, with in vivo testing limited to a single mouse model (E. coli sepsis). Pharmacokinetics, toxicity, and stability of these peptides in mammalian systems are not fully characterized. The bacterial expression system may produce peptides with different properties than native insect peptides. Only one peptide (Rip-2) was tested in vivo. Clinical translation from insect peptides to human therapeutics faces significant development hurdles."},{"rthcId":"RPEP-09029","title":"Rumicidins are a family of mammalian host-defense peptides plugging the 70S ribosome exit tunnel.","authors":"Panteleev, Pavel V; Pichkur, Eugene B; Kruglikov, Roman N; Paleskava, Alena; Shulenina, Olga V; Bolosov, Ilia A; Bogdanov, Ivan V; Safronova, Victoria N; Balandin, Sergey V; Marina, Valeriya I; Kombarova, Tatiana I; Korobova, Olga V; Shamova, Olga V; Myasnikov, Alexander G; Borzilov, Alexander I; Osterman, Ilya A; Sergiev, Petr V; Bogdanov, Alexey A; Dontsova, Olga A; Konevega, Andrey L; Ovchinnikova, Tatiana V","year":2024,"journal":"Nature communications, 15(1), 8925","doi":"10.1038/s41467-024-53309-y","pmid":"39414793","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Genome mining revealed rumicidin genes widespread among ruminant mammals. The peptides belong to the proline-rich cathelicidin family and kill bacteria by inhibiting the elongation stage of translation (protein synthesis).\n\nCryo-EM structural analysis of the E. coli 70S ribosome bound to a rumicidin revealed that the peptide spans the ribosomal A-site cleft and plugs into the nascent peptide exit tunnel, interacting with its constriction point via a conserved Trp23-Phe24 dyad. Bacterial resistance mechanisms involve knockout of the SbmA transporter (needed for peptide uptake) or modification of the MacAB-TolC efflux pump. The peptides demonstrated broad-spectrum antibacterial activity, efficacy in an animal infection model, and no adverse effects on human cells in vitro.","whyItMatters":"The antimicrobial resistance crisis demands new antibiotics with novel mechanisms of action. Rumicidins represent a new antibiotic class that works by a well-defined structural mechanism — plugging the ribosome exit tunnel — which is distinct from most existing antibiotics. The combination of broad-spectrum activity, in vivo efficacy, lack of human cell toxicity, and atomic-resolution structural data makes them unusually complete candidates for antibiotic development. Published in Nature Communications, this represents a high-impact discovery in the antimicrobial peptide field.","specificNumbers":"","methodology":"The researchers used genome mining to identify rumicidin genes across ruminant genomes. Peptides were produced and tested biochemically for translation inhibition using in vitro translation assays. The structural mechanism was determined by cryo-electron microscopy of the E. coli 70S ribosome-rumicidin complex. Antibacterial spectrum was assessed through standard susceptibility testing against multiple bacterial species. In vivo efficacy was tested in an animal infection model. Cytotoxicity to human cells was evaluated in vitro. Resistance mechanisms were characterized using bacterial knockout mutants.","limitations":"While in vivo efficacy was demonstrated in an animal infection model, the specific model, dosing, and bacterial challenge details were not provided in the abstract. The SbmA transporter-dependent uptake pathway is a known vulnerability of PrAMPs — bacteria can develop resistance by losing this transporter. The identified efflux pump modification represents another resistance concern. Human pharmacokinetics, stability, and potential immunogenicity of these peptides in therapeutic use remain unknown. Translation from animal-derived peptides to human therapeutics requires extensive optimization."},{"rthcId":"RPEP-09030","title":"Acute, chronic and conditioned effects of intranasal oxytocin in the mu-opioid receptor knockout mouse model of autism: Social context matters.","authors":"Pantouli, Fani; Pujol, Camille N; Derieux, Cécile; Fonteneau, Mathieu; Pellissier, Lucie P; Marsol, Claire; Karpenko, Julie; Bonnet, Dominique; Hibert, Marcel; Bailey, Alexis; Le Merrer, Julie; Becker, Jerome A J","year":2024,"journal":"Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 49(12), 1934-1946","doi":"10.1038/s41386-024-01915-1","pmid":"39020142","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Acute intranasal oxytocin at 0.3 IU improved social behavior in Oprm1 knockout mice (autism model) within 5 minutes of administration, with limited effects on non-social behaviors like anxiety or stereotypies.\n\nChronic oxytocin (8-17 days) maintained its rescuing effects in knockout mice but was deleterious in wild-type mice — an important safety finding. Most importantly, when oxytocin was administered in a social context (paired with social interaction), improvements in social behavior were both greater and longer-lasting compared to oxytocin given without social experience. Under these conditions, expression of oxytocin and vasopressin receptor genes and striatal neuron markers was suppressed. No sex differences in oxytocin effects were detected.","whyItMatters":"Clinical trials of oxytocin for autism have been largely disappointing, but this study suggests the problem may not be the drug itself — it may be how it's used. If oxytocin's social benefits are context-dependent (requiring concurrent social interaction to work optimally), then clinical trials giving oxytocin without structured social experiences may have been set up to fail. This finding could fundamentally reshape how oxytocin-based therapies are designed and tested in humans with autism.","specificNumbers":"","methodology":"Researchers used Oprm1 knockout mice (lacking the mu-opioid receptor) as an established model of autism-like behavior. Intranasal oxytocin was tested at three doses (0.15, 0.3, 0.6 IU) and three time points (5, 15, 30 min post-administration) in both knockout and wild-type mice. Behaviors assessed included social interaction, social preference, stereotypies, anxiety, and pain sensitivity. Chronic administration was tested over 8-17 days. A conditioned paradigm paired oxytocin with social experience. Gene expression was measured in brain reward and social circuits.","limitations":"This is a mouse study using a single genetic model of autism (Oprm1 knockout), which captures only a narrow slice of the complex and heterogeneous human autism spectrum. The intranasal delivery in mice involves much more direct nasal-brain exposure than in humans. The beneficial dose range was narrow (only 0.3 IU was effective), and the harmful effects of chronic dosing in wild-type mice raise safety concerns that need investigation. The gene expression changes measured in the brain provide mechanistic clues but don't confirm specific molecular mechanisms."},{"rthcId":"RPEP-09031","title":"Spotlight on the Mechanism of Action of Semaglutide.","authors":"Papakonstantinou, Ilias; Tsioufis, Konstantinos; Katsi, Vasiliki","year":2024,"journal":"Current issues in molecular biology, 46(12), 14514-14541","doi":"10.3390/cimb46120872","pmid":"39728000","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09032","title":"Effectiveness of integrating a pragmatic pathway for prescribing liraglutide 3.0 mg in weight management services (STRIVE study): a multicentre, open-label, parallel-group, randomized controlled trial.","authors":"Papamargaritis, Dimitris; Al-Najim, Werd; Lim, Jonathan Z M; Crane, James; Bodicoat, Danielle H; Barber, Shaun; Lean, Michael; McGowan, Barbara; O'Shea, Donal; Webb, David R; Wilding, John P H; le Roux, Carel W; Davies, Melanie J","year":2024,"journal":"The Lancet regional health. Europe, 39, 100853","doi":"10.1016/j.lanepe.2024.100853","pmid":"38803628","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09033","title":"Substance P concentration is associated with the inflammatory response and pain perception in patients with chronic pain in peripheral artery disease.","authors":"Paplaczyk-Serednicka, Małgorzata; Markowska, Beata; Gach, Tomasz; Bogacki, Paweł; Szura, Mirosław; Bonior, Joanna","year":2024,"journal":"Polski przeglad chirurgiczny, 96(4), 15-24","doi":"10.5604/01.3001.0054.2682","pmid":"39138987","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09034","title":"Assessment of Bone Mineral Density Over 1 Year in a Cross-Sectional Cohort of Migraine Patients Receiving Anti-CGRP Monoclonal Antibodies.","authors":"Para, Davide; Camponovo, Chiara; Riccitelli, Gianna Carla; Mallucci, Giulia; Maino, Paolo; Mondini Trissino da Lodi, Camilla; Saudina, Demurtas; Trimboli, Pierpaolo; Gobbi, Claudio; Zecca, Chiara","year":2024,"journal":"CNS drugs, 38(10), 819-825","doi":"10.1007/s40263-024-01104-0","pmid":"39174745","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 51 migraine patients (43 female, mean age 46 years) treated with anti-CGRP monoclonal antibodies for an average of 15.7 months, 53% had bone density abnormalities (22 with osteopenia, 5 with osteoporosis). However, logistic regression analysis found no association between anti-CGRP treatment duration and bone density abnormalities.\n\nThe significant predictors of reduced bone density were menopause (OR 11.641, 95% CI 1.486–91.197, p=0.019) and anti-seizure drug use (OR 12.825, 95% CI 1.162–141.569, p=0.037) — both well-established risk factors for osteoporosis independent of CGRP therapy.","whyItMatters":"Anti-CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab) are among the most important advances in migraine treatment in decades, but since CGRP promotes bone formation, there's been legitimate concern that blocking it long-term could cause bone loss. This is the first study specifically examining this safety question, and the initial findings are reassuring — though the small size means the question remains open.","specificNumbers":"","methodology":"This was a single-center, cross-sectional cohort study of migraine patients who underwent bone densitometry (DEXA scan) during anti-CGRP antibody treatment. Patients were classified as OSTEO+ (T-score ≤ -1) or normal. The association between OSTEO+ status, anti-CGRP treatment duration, and established osteoporosis risk factors was analyzed using logistic regression models.","limitations":"The study had a small sample size (51 patients) with wide confidence intervals on the odds ratios, limiting statistical power. The cross-sectional design cannot establish causation or detect gradual changes over time. There was no baseline bone density measurement before starting anti-CGRP treatment. The mean treatment duration of 15.7 months may be too short to detect bone effects. The single-center design limits generalizability."},{"rthcId":"RPEP-09035","title":"Exendin-4 exhibits cardioprotective effects against high glucose-induced mitochondrial abnormalities: Potential role of GLP-1 receptor and mTOR signaling.","authors":"Parichatikanond, Warisara; Pandey, Sudhir; Mangmool, Supachoke","year":2024,"journal":"Biochemical pharmacology, 229, 116552","doi":"10.1016/j.bcp.2024.116552","pmid":"39307319","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09036","title":"Current Advancements on Oral Protein and Peptide Drug Delivery Approaches to Bioavailability: Extensive Review on Patents.","authors":"Parida, Prasanna; Prusty, Amiya Kumar; Patro, Saroj Kumar; Jena, Bikash Ranjan","year":2024,"journal":"Recent advances in drug delivery and formulation, 18(4), 227-246","doi":"10.2174/0126673878299775240719061653","pmid":"39356096","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09037","title":"GLP-1 receptor agonists and atherosclerosis protection: the vascular endothelium takes center stage.","authors":"Park, Brady; Bakbak, Ehab; Teoh, Hwee; Krishnaraj, Aishwarya; Dennis, Fallon; Quan, Adrian; Rotstein, Ori D; Butler, Javed; Hess, David A; Verma, Subodh","year":2024,"journal":"American journal of physiology. Heart and circulatory physiology, 326(5), H1159-H1176","doi":"10.1152/ajpheart.00574.2023","pmid":"38426865","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09038","title":"GLP-1 and Its Derived Peptides Mediate Pain Relief Through Direct TRPV1 Inhibition Without Affecting Thermoregulation.","authors":"Park, Chul-Kyu; Go, Eun Jin; Jo, Hyunjung; Hwang, Sung-Min; Rahman, Md Mahbubur; Park, Jaeik; Lee, Ji Yeon; Jo, Youn Yi; Jung, YunJae; Berta, Temugin; Kim, Yong Ho","year":2024,"journal":"Research square","doi":"10.21203/rs.3.rs-4233732/v1","pmid":"38798444","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09039","title":"Gastrin-releasing peptide receptor antagonist RC-3095 inhibits Porphyromonas gingivalis lipopolysaccharide-accelerated atherosclerosis by suppressing inflammatory responses in endothelial cells and macrophages.","authors":"Park, Hyun-Joo; Kim, Mi-Kyoung; Kim, Yeon; Kim, Hyung Joon; Park, Hae Ryoun; Bae, Soo-Kyung; Bae, Moon-Kyoung","year":2024,"journal":"Inflammation research : official journal of the European Histamine Research Society ... [et al.], 73(11), 1833-1846","doi":"10.1007/s00011-024-01934-0","pmid":"39164592","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"RC-3095 significantly reduced P. gingivalis LPS-induced leukocyte adhesion to endothelial cells by suppressing NF-κB-dependent expression of adhesion molecules ICAM-1 and VCAM-1. It also blocked M1 macrophage polarization by inhibiting both MAPK and NF-κB signaling pathways.\n\nIn ApoE-knockout mice on a high-fat diet, RC-3095 decreased the area of atherosclerotic lesions that were accelerated by P. gingivalis LPS injections, and lowered ICAM-1 and VCAM-1 expression in aortic tissue. These results demonstrate that blocking the gastrin-releasing peptide receptor interrupts multiple inflammatory steps in bacteria-driven atherosclerosis.","whyItMatters":"The link between periodontal disease and cardiovascular disease is well established but poorly treated. Current approaches address either the gum infection or the heart disease separately. RC-3095 targets the inflammatory connection between the two, potentially offering a novel therapeutic strategy that addresses the root cause of bacteria-driven cardiovascular damage through peptide receptor modulation.","specificNumbers":"","methodology":"Researchers tested RC-3095 in three systems: (1) human umbilical vein endothelial cells (HUVECs) and rat aortic endothelium to assess leukocyte adhesion; (2) THP-1 cells polarized into M1 macrophages by bacterial LPS exposure; and (3) ApoE-knockout mice on a high-fat diet receiving P. gingivalis LPS injections with or without RC-3095. Atherosclerotic lesion area, adhesion molecule expression, and inflammatory signaling pathways were assessed.","limitations":"This is a preclinical study using cell cultures and a mouse atherosclerosis model. ApoE-knockout mice develop artificially accelerated atherosclerosis that differs from human disease progression. The P. gingivalis LPS injection model doesn't fully replicate chronic human periodontal disease. Dosing, pharmacokinetics, and potential off-target effects of RC-3095 in humans were not assessed."},{"rthcId":"RPEP-09040","title":"Exploring the Therapeutic Potential of Scorpion-Derived Css54 Peptide Against Candida albicans.","authors":"Park, Jonggwan; Kim, Hyeongsun; Kang, Da Dam; Park, Yoonkyung","year":2024,"journal":"Journal of microbiology (Seoul, Korea), 62(2), 101-112","doi":"10.1007/s12275-024-00113-4","pmid":"38589765","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09041","title":"Machine Learning-Based Plasma Metabolomics in Liraglutide-Treated Type 2 Diabetes Mellitus Patients and Diet-Induced Obese Mice.","authors":"Park, Seokjae; Kim, Eun-Kyoung","year":2024,"journal":"Metabolites, 14(9)","doi":"10.3390/metabo14090483","pmid":"39330490","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09042","title":"Glucagonlike Peptide-1 Receptor Agonists: The Good, the Bad, and the Ugly-Benefits for Glucose Control and Weight Loss with Side Effects of Delaying Gastric Emptying.","authors":"Parkman, Henry P; Rim, Daniel S; Anolik, Jonathan R; Dadparvar, Simin; Maurer, Alan H","year":2024,"journal":"Journal of nuclear medicine technology, 52(1), 3-7","doi":"10.2967/jnmt.123.266800","pmid":"38443105","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09043","title":"FRAP analysis of peptide diffusion in extracellular matrix mimetic hydrogels as an in vitro model for subcutaneous injection.","authors":"Parlow, Julia; Rodler, Agnes; Gråsjö, Johan; Sjögren, Helen; Hansson, Per","year":2024,"journal":"International journal of pharmaceutics, 664, 124628","doi":"10.1016/j.ijpharm.2024.124628","pmid":"39179009","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09044","title":"Antiviral activity of cathelicidins against porcine epidemic diarrhea virus (PEDV): Mechanisms, and efficacy.","authors":"Pashaie, Fatemeh; Hoornweg, Tabitha E; Bikker, Floris J; Veenendaal, Tineke; Broere, Femke; Veldhuizen, Edwin J A","year":2024,"journal":"Virus research, 350, 199496","doi":"10.1016/j.virusres.2024.199496","pmid":"39528011","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"LL-37 (human) and CATH-B1 (chicken) cathelicidins significantly reduced PEDV infection of Vero cells at non-toxic concentrations of 5 and 10 µM, effective in both co-incubation (simultaneous) and pre-incubation setups. Transmission electron microscopy revealed that both peptides directly altered virus morphology and caused aggregation of viral particles, reducing infectivity.\n\nFluorogenic LL-37 was observed entering cells, suggesting a possible immunomodulatory component to its antiviral action. In stark contrast, none of the four porcine cathelicidins (PMAP-36, PMAP-23, PR-39, PG-1) showed any inhibitory effects against PEDV, even at higher concentrations.","whyItMatters":"PEDV causes massive losses in the global pig industry and no effective antiviral treatments exist. This study identifies two cathelicidin peptides that effectively neutralize the virus and reveals their mechanism — direct disruption of viral particles. The surprising finding that pig-derived peptides don't work against a pig virus while human and chicken peptides do raises important questions about host-pathogen co-evolution and could guide development of novel antiviral peptide therapies.","specificNumbers":"","methodology":"The researchers tested six cathelicidin antimicrobial peptides against GFP-tagged PEDV in Vero cell cultures. Antiviral activity was measured using flow cytometry and fluorescent microscopy in both co-incubation and pre-incubation setups. Peptide entry into cells was tracked using fluorogenic LL-37. Virus morphology changes were visualized with transmission electron microscopy. Cytotoxicity was assessed to ensure peptides were used at non-toxic concentrations.","limitations":"This is an in vitro study using Vero cells (monkey kidney cells), not pig intestinal cells where PEDV naturally infects. The study does not include in vivo animal experiments, so it is unknown whether LL-37 or CATH-B1 could effectively treat PEDV infection in live pigs. The concentrations effective in cell culture may not be achievable in the pig gut. Additionally, PEDV primarily infects intestinal epithelium, and peptide stability in the GI environment was not assessed."},{"rthcId":"RPEP-09045","title":"Thermodynamic Study on Biomimetic Legionella gormanii Bacterial Membranes.","authors":"Pastuszak, Katarzyna; Palusińska-Szysz, Marta; Wiącek, Agnieszka Ewa; Jurak, Małgorzata","year":2024,"journal":"Molecules (Basel, Switzerland), 29(18)","doi":"10.3390/molecules29184367","pmid":"39339363","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09046","title":"Gastrointestinal adverse events and weight reduction in people with type 2 diabetes treated with tirzepatide in the SURPASS clinical trials.","authors":"Patel, Hiren; Khunti, Kamlesh; Rodbard, Helena W; Bajaj, Harpreet S; Bray, Ross; Kindracki, Zbigniew; Rodríguez, Ángel","year":2024,"journal":"Diabetes, obesity & metabolism, 26(2), 473-481","doi":"10.1111/dom.15333","pmid":"37853960","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09047","title":"Cell-penetrating peptides for sustainable agriculture.","authors":"Patel, Preeti; Benzle, Kyle; Pei, Dehua; Wang, Guo-Liang","year":2024,"journal":"Trends in plant science, 29(10), 1131-1144","doi":"10.1016/j.tplants.2024.05.011","pmid":"38902122","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09048","title":"GnRH Peptide Antagonist: Comparative Analysis of Chemistry and Formulation with Implications for Clinical Safety and Efficacy.","authors":"Patel, Shikha; Saxena, Bhagawati; Mehta, Priti; Niazi, Sarfaraz K","year":2024,"journal":"Pharmaceuticals (Basel, Switzerland), 18(1)","doi":"10.3390/ph18010036","pmid":"39861098","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09049","title":"Preclinical pharmacokinetics, pharmacodynamics, and toxicity of novel small-molecule GPR119 agonists to treat type-2 diabetes and obesity.","authors":"Patil, Mohan; Casari, Ilaria; Thapa, Dinesh; Warne, Leon N; Dallerba, Elena; Massi, Massimiliano; Carlessi, Rodrigo; Falasca, Marco","year":2024,"journal":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 177, 117077","doi":"10.1016/j.biopha.2024.117077","pmid":"38968799","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09050","title":"Therapeutic Advances in Obesity: How Real-World Evidence Impacts Affordability Beyond Standard of Care.","authors":"Patoulias, Dimitrios; Koufakis, Theocharis; Ruža, Ieva; El-Tanani, Mohamed; Rizzo, Manfredi","year":2024,"journal":"Pragmatic and observational research, 15, 139-149","doi":"10.2147/POR.S471476","pmid":"39130529","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review confirms that semaglutide, liraglutide, and tirzepatide demonstrate meaningful weight reduction in real-world settings, consistent with clinical trial results. All three agents show pleiotropic (multi-system) benefits beyond weight loss, including cardiovascular and metabolic improvements. However, the high cost of these medications remains a significant barrier to widespread adoption. Real-world evidence suggests that while efficacy is maintained outside trial settings, affordability and access limitations prevent these drugs from reaching the majority of people who could benefit.","whyItMatters":"Clinical trials show what a drug can do under ideal conditions; real-world evidence shows what it actually does in routine practice with diverse patient populations. This review bridges that gap for the three most important obesity medications available today. The affordability question is equally critical — even the most effective drug can't address a global epidemic if most patients can't access it.","specificNumbers":"","methodology":"Narrative review article synthesizing published real-world evidence and cost-effectiveness data for approved GLP-1 receptor agonists (semaglutide, liraglutide) and the dual GIP/GLP-1 agonist tirzepatide in obesity treatment. The review focused on studies conducted outside randomized controlled trial settings to assess real-world effectiveness and economic feasibility.","limitations":"As a narrative review, the methodology for study selection and synthesis is not as rigorous as a systematic review. The rapidly evolving pricing landscape and ongoing insurance coverage changes may make cost-effectiveness conclusions quickly outdated. Real-world evidence is inherently subject to selection bias and confounding. The review may not capture the most recent data given the fast pace of publication in this field."},{"rthcId":"RPEP-09051","title":"De-Intensification from Basal-Bolus Insulin Therapy to Liraglutide in Type 2 Diabetes: Predictive Value of Mean Glycaemia during Fasting Test.","authors":"Pavlikova, Barbora; Breburdova, Martina; Krcma, Michal; Kriz, Miroslav; Kasparek, Jan; Rusavy, Zdenek","year":2024,"journal":"Life (Basel, Switzerland), 14(5)","doi":"10.3390/life14050568","pmid":"38792590","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09052","title":"A comparison of heart failure patients with reduced ejection fraction in the Moravian Midlands Registry with the LCZ696 patients in the Paradigm-HF trial.","authors":"Pavlu, Ludek; Vicha, Marek; Flasik, Jakub; Petrkova, Jana; Taborsky, Milos; Kacirkova, Tereza; Holy, Ondrej","year":2024,"journal":"Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia, 168(3), 229-234","doi":"10.5507/bp.2023.006","pmid":"36748670","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09053","title":"The multiple actions of dipeptidyl peptidase 4 (DPP-4) and its pharmacological inhibition on bone metabolism: a review.","authors":"Pechmann, L M; Pinheiro, F I; Andrade, V F C; Moreira, C A","year":2024,"journal":"Diabetology & metabolic syndrome, 16(1), 175","doi":"10.1186/s13098-024-01412-x","pmid":"39054499","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09054","title":"Intentional weight loss in overweight and obese patients with heart failure: A systematic review.","authors":"Peck, Kah Hua; Dulay, Mansimran Singh; Hameed, Saira; Rosano, Giuseppe; Tan, Tricia; Dar, Owais","year":2024,"journal":"European journal of heart failure, 26(9), 1907-1930","doi":"10.1002/ejhf.3270","pmid":"38752254","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09055","title":"Characterisation of defensins across the marsupial family tree.","authors":"Peel, Emma; Hogg, Carolyn; Belov, Katherine","year":2024,"journal":"Developmental and comparative immunology, 158, 105207","doi":"10.1016/j.dci.2024.105207","pmid":"38797458","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09056","title":"Combining treatments for migraine prophylaxis: the state-of-the-art.","authors":"Pellesi, Lanfranco; Garcia-Azorin, David; Rubio-Beltrán, Eloisa; Ha, Wook-Seok; Messina, Roberta; Ornello, Raffaele; Petrusic, Igor; Raffaelli, Bianca; Labastida-Ramirez, Alejandro; Ruscheweyh, Ruth; Tana, Claudio; Vuralli, Doga; Waliszewska-Prosół, Marta; Wang, Wei; Wells-Gatnik, William","year":2024,"journal":"The journal of headache and pain, 25(1), 214","doi":"10.1186/s10194-024-01925-w","pmid":"39639191","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Dual CGRP inhibition — combining monoclonal antibodies targeting CGRP or its receptor with oral gepant antagonists — may enhance efficacy by blocking the CGRP pain pathway at multiple points. Combining onabotulinumtoxin A with CGRP-targeted treatments offers potentially synergistic pain relief through complementary mechanisms.\n\nTraditional oral preventives (non-CGRP treatments) remain a practical and affordable combination partner, especially for patients with comorbid conditions. Despite these promising strategies, the review found insufficient evidence to support their routine inclusion in clinical guidelines, and the high cost of biological combination regimens poses feasibility challenges.","whyItMatters":"Many migraine patients do not achieve adequate relief from a single preventive treatment. As the toolkit of migraine-specific therapies expands — particularly CGRP-targeted biologics and gepants — clinicians need evidence-based guidance on which combinations are safe, effective, and cost-justified. This review maps the current landscape and highlights where the biggest evidence gaps remain.","specificNumbers":"","methodology":"This is a state-of-the-art narrative review synthesizing available evidence on combination migraine prophylaxis strategies, including oral conventional preventives, onabotulinumtoxin A, CGRP-targeting monoclonal antibodies, and gepants. The review was authored by an international panel of headache specialists.","limitations":"This is a narrative review, not a systematic review or meta-analysis. Most evidence for combination strategies comes from small studies, retrospective analyses, or case series rather than large randomized controlled trials. The review acknowledges that high costs of biologic combinations may limit real-world adoption regardless of efficacy. Long-term safety data for many combinations is lacking."},{"rthcId":"RPEP-09057","title":"Onabotulinumtoxin A for the Treatment of Post-Traumatic Headache: Is It Better than Anti-CGRP Antibodies?","authors":"Pellesi, Lanfranco; Onan, Dilara; Martelletti, Paolo","year":2024,"journal":"Toxins, 16(10)","doi":"10.3390/toxins16100427","pmid":"39453203","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A Phase 2 trial of fremanezumab (anti-CGRP mAb) failed to demonstrate significant efficacy in post-traumatic headache, despite its proven effectiveness in migraine. Evidence for onabotulinumtoxin A in PTH is limited to one small trial with abobotulinumtoxin A in 40 subjects. The review concludes that CGRP inhibition alone may be insufficient for PTH due to the condition's complex, multi-pathway pathophysiology, while ONA's broader mechanism (affecting multiple pain pathways) may offer advantages. ONA also has potential cost-effectiveness and adherence benefits.","whyItMatters":"Post-traumatic headache affects up to 90% of TBI patients and can persist for years, yet has no approved treatments. The failure of CGRP-blocking drugs — which revolutionized migraine treatment — to work in PTH reveals that not all headaches are created equal. This has major implications for the millions of people with traumatic brain injuries (military personnel, athletes, accident victims) who need effective headache treatment.","specificNumbers":"","methodology":"Comprehensive literature review searching PubMed through September 2024 for studies on onabotulinumtoxin A and anti-CGRP mAbs in post-traumatic headache. Both clinical trials and observational studies were reviewed.","limitations":"Very limited evidence base — only one small trial for botulinum toxin and one Phase 2 trial for anti-CGRP in PTH. Current treatment strategies are extrapolated from other headache disorders, not validated for PTH. The fremanezumab trial failure could reflect trial design issues rather than definitive proof that CGRP targeting doesn't work. The review is narrative, not systematic."},{"rthcId":"RPEP-09058","title":"Design, synthesis, and analysis of macrobicyclic peptides for targeting the Gαi protein.","authors":"Pepanian, Anna; Binbay, F Ayberk; Pei, Dehua; Imhof, Diana","year":2024,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 30(6), e3565","doi":"10.1002/psc.3565","pmid":"38232955","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09059","title":"Role of GLP1-RA in Optimizing Weight Loss Post-Bariatric Surgery: A Systematic Review and Meta-Analysis.","authors":"Pereira, Mable; Menezes, Shenelle; Franco, Ancy Jenil; Marcolin, Patricia; Tomera, Mark","year":2024,"journal":"Obesity surgery, 34(10), 3888-3896","doi":"10.1007/s11695-024-07486-w","pmid":"39215779","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09060","title":"An update on pharmacotherapy for trigeminal neuralgia.","authors":"Pergolizzi, Joseph V; LeQuang, Jo Ann; El-Tallawy, Salah N; Wagner, Morgan; Ahmed, Rania S; Varrassi, Giustino","year":2024,"journal":"Expert review of neurotherapeutics, 24(8), 773-786","doi":"10.1080/14737175.2024.2365946","pmid":"38870050","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09061","title":"Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes.","authors":"Perkovic, Vlado; Tuttle, Katherine R; Rossing, Peter; Mahaffey, Kenneth W; Mann, Johannes F E; Bakris, George; Baeres, Florian M M; Idorn, Thomas; Bosch-Traberg, Heidrun; Lausvig, Nanna Leonora; Pratley, Richard","year":2024,"journal":"The New England journal of medicine, 391(2), 109-121","doi":"10.1056/NEJMoa2403347","pmid":"38785209","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09062","title":"Impressive Response to TANDEM Peptide Receptor Radionuclide Therapy with 177Lu/225AcDOTA-LM3 Somatostatin Receptor Antagonist in a Patient with Therapy-Refractory, Rapidly Progressive Neuroendocrine Neoplasm of the Pancreas.","authors":"Perrone, Elisabetta; Ghai, Kriti; Eismant, Aleksandr; Andreassen, Mikkel; Langer, Seppo W; Knigge, Ulrich; Kjaer, Andreas; Baum, Richard P","year":2024,"journal":"Diagnostics (Basel, Switzerland), 14(9)","doi":"10.3390/diagnostics14090907","pmid":"38732321","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A 58-year-old woman with rapidly progressive, therapy-refractory neuroendocrine pancreatic tumor (grade G3) with extensive liver, bone, and lymph node metastases received three cycles of TANDEM peptide receptor radionuclide therapy (PRRT) using concurrently administered [177Lu]Lu-DOTA-LM3 and [225Ac]Ac-DOTA-LM3, a somatostatin receptor antagonist. The treatment produced complete regression of bone and lymph node metastases, significant reduction in liver metastases and hepatomegaly, and improvement in the primary pancreatic tumor. Partial remission was confirmed across multiple imaging modalities (PET/CT, contrast-enhanced CT, and abdominal MRI), with marked clinical improvement in pain, energy levels, and quality of life, enabling the patient to fully resume physical activity.","whyItMatters":"This case demonstrates the potential of TANDEM-PRRT using a somatostatin receptor antagonist (LM3) in a patient who had already exhausted multiple standard treatments including conventional PRRT with [177Lu]Lu-DOTATATE, chemotherapy, targeted therapy (Everolimus), somatostatin analogs, and liver embolization. The dramatic response suggests that receptor antagonists may bind to more receptor sites than traditional agonists, and that combining lutetium-177 with actinium-225 in a tandem approach could offer a powerful salvage option for patients with no remaining standard therapies.","specificNumbers":"3 TANDEM-PRRT cycles · Complete regression of bone and lymph node metastases · Partial remission confirmed on PET/CT, CE-CT, and MRI","methodology":"Single-patient case report. A 58-year-old woman with therapy-refractory grade G3 neuroendocrine pancreatic tumor underwent [68Ga]Ga-DOTA-LM3 PET/CT for receptor imaging, followed by three cycles of concurrent [177Lu]Lu-DOTA-LM3 and [225Ac]Ac-DOTA-LM3 TANDEM-PRRT. Response was assessed via PET/CT, contrast-enhanced CT of the chest-abdomen-pelvis, and abdominal MRI.","limitations":"As a single case report, these results cannot be generalized to other patients. There is no control comparison, and long-term durability of the response is not described. The specific doses and intervals between TANDEM-PRRT cycles are not detailed in the abstract."},{"rthcId":"RPEP-09063","title":"Risk of treatment-altering haematological toxicity and its dependence on bone marrow doses in peptide receptor radionuclide therapy.","authors":"Persson, Märta; Hindorf, Cecilia; Ardenfors, Oscar; Larsson, Martin; Nilsson, Joachim N","year":2024,"journal":"EJNMMI research, 14(1), 13","doi":"10.1186/s13550-024-01077-7","pmid":"38319478","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09064","title":"Recent advances in diagnosing, managing, and understanding the pathophysiology of cluster headache.","authors":"Petersen, Anja S; Lund, Nunu; Goadsby, Peter J; Belin, Andrea C; Wang, Shuu-Jiun; Fronczek, Rolf; Burish, Mark; Cho, Soo-Jin; Peres, Mario F P; Jensen, Rigmor H","year":2024,"journal":"The Lancet. Neurology, 23(7), 712-724","doi":"10.1016/S1474-4422(24)00143-1","pmid":"38876749","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09065","title":"Molecular determinants of neuropeptide-mediated activation mechanisms in tachykinin NK1 and NK2 receptors.","authors":"Petersen, Jacob E; Pavlovskyi, Artem; Madsen, Jesper J; Schwartz, Thue W; Frimurer, Thomas M; Olsen, Ole H","year":2024,"journal":"The Journal of biological chemistry, 300(12), 107948","doi":"10.1016/j.jbc.2024.107948","pmid":"39481599","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09066","title":"Lead-in calorie restriction enhances the weight-lowering efficacy of incretin hormone-based pharmacotherapies in mice.","authors":"Petersen, Jonas; Merrild, Christoffer; Lund, Jens; Holm, Stephanie; Clemmensen, Christoffer","year":2024,"journal":"Molecular metabolism, 89, 102027","doi":"10.1016/j.molmet.2024.102027","pmid":"39265725","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09067","title":"Interactions of Oxytocin and Dopamine-Effects on Behavior in Health and Disease.","authors":"Petersson, Maria; Uvnäs-Moberg, Kerstin","year":2024,"journal":"Biomedicines, 12(11)","doi":"10.3390/biomedicines12112440","pmid":"39595007","tags":[],"studyType":"review","evidenceStrength":"review","keyFinding":"Oxytocin (a peptide) and dopamine (a monoamine) are structurally completely different but share remarkably similar behavioral effects. Both are released during social interaction, sex, feeding, and massage, and both influence reward, motivation, and bonding. Critically, they affect each other's release and receptors, creating a bidirectional interaction network.\n\nDeviations in both systems are associated with the same psychiatric conditions: anxiety, autism spectrum disorders, depression, ADHD, and schizophrenia. The review maps how these two chemically distinct signaling molecules converge on overlapping behavioral circuits, suggesting that many of oxytocin's effects on social behavior may be partially mediated through dopamine pathways and vice versa.","whyItMatters":"Oxytocin is often studied in isolation as the 'social bonding' peptide, while dopamine is studied separately as the 'reward' neurotransmitter. This review reveals they're deeply intertwined — each modulating the other's release and receptor activity. This has profound implications for treating psychiatric disorders: targeting oxytocin alone may fail if the dopamine interaction isn't considered, and dopamine-based treatments (like those for ADHD or schizophrenia) may be partially working through oxytocin pathways.","specificNumbers":"Both released during social interaction, sex, feeding, massage · Both associated with anxiety, ASD, depression, ADHD, schizophrenia · Bidirectional modulation of release and receptors · Produced both centrally and peripherally","methodology":"Narrative review examining published research on the interactions between oxytocin and dopamine systems, with focus on behavioral effects, mutual regulation of release and receptors, and roles in psychiatric disorders and functional diversities.","limitations":"As a narrative review, study selection is not systematic. The abstract acknowledges structural differences but the interaction mechanisms are complex and not fully elucidated. Most evidence for oxytocin-dopamine interactions comes from animal studies, with limited human data on receptor-level interactions. Co-authored by Kerstin Uvnäs-Moberg, a prominent oxytocin researcher, which may reflect a particular perspective."},{"rthcId":"RPEP-09068","title":"Semaglutide and NT-proBNP in Obesity-Related HFpEF: Insights From the STEP-HFpEF Program.","authors":"Petrie, Mark C; Borlaug, Barry A; Butler, Javed; Davies, Melanie J; Kitzman, Dalane W; Shah, Sanjiv J; Verma, Subodh; Jensen, Thomas Jon; Einfeldt, Mette Nygaard; Liisberg, Karoline; Perna, Eduardo; Sharma, Kavita; Ezekowitz, Justin A; Fu, Michael; Melenovský, Vojtěch; Ito, Hiroshi; Lelonek, Małgorzata; Kosiborod, Mikhail N","year":2024,"journal":"Journal of the American College of Cardiology, 84(1), 27-40","doi":"10.1016/j.jacc.2024.04.022","pmid":"38819334","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09069","title":"Impact of semaglutide and dulaglutide shortages on Pharmaceutical Benefits Scheme prescriptions supplied for type 2 diabetes treatment.","authors":"Phakey, Sachin; Shen, Angeline","year":2024,"journal":"Australian journal of general practice, 53(1-2), 57-61","doi":"10.31128/AJGP/04-23-6814","pmid":"38316483","tags":["glp-1-agonists","semaglutide"],"studyType":"retrospective-analysis","evidenceStrength":"moderate","keyFinding":"When semaglutide supply shortages hit Australia in 2022, prescriptions dropped 17% while dulaglutide prescriptions surged 53% as doctors switched patients to the available alternative. The shortages resulted in approximately 119,069 fewer semaglutide prescriptions than predicted over a 4-month period. When dulaglutide also experienced shortages shortly after, its prescriptions dropped 17% as well, leaving type 2 diabetes patients with limited GLP-1 agonist options.","whyItMatters":"The GLP-1 agonist shortage affected millions of diabetes patients worldwide, and this Australian data quantifies the real-world impact. When one drug becomes unavailable, the surge in demand for alternatives can trigger cascading shortages. This pattern highlights the vulnerability of diabetes care when it depends on a small number of peptide drugs from limited manufacturing sources.","specificNumbers":"119,069 fewer semaglutide prescriptions than predicted · 17% semaglutide decrease · 53% dulaglutide increase · 31,953 more dulaglutide prescriptions than predicted","methodology":"Researchers performed a retrospective analysis of Australian Pharmaceutical Benefits Scheme (PBS) prescription data for 2021-2022. They used Holt-Winters statistical modeling to predict expected prescription volumes and compared these predictions against actual prescriptions supplied, identifying the gap caused by supply shortages.","limitations":"This is an Australian-specific analysis that may not directly reflect shortage patterns in other countries. The study used prescription data rather than patient outcomes, so it can't assess whether the shortages caused harm to individual patients. The Holt-Winters model assumes continuation of prior trends, which may not account for organic changes in prescribing behavior unrelated to shortages."},{"rthcId":"RPEP-09070","title":"Delivery to, and Reactivation of, the p53 Pathway in Cancer Cells Using a Grafted Cyclotide Conjugated with a Cell-Penetrating Peptide.","authors":"Philippe, Grégoire Jean-Baptiste; Huang, Yen-Hua; Mittermeier, Anna; Brown, Christopher J; Kaas, Quentin; Ramlan, Siti Radhiah; Wang, Conan K; Lane, David; Loewer, Alexander; Troeira Henriques, Sónia; Craik, David J","year":2024,"journal":"Journal of medicinal chemistry, 67(2), 1197-1208","doi":"10.1021/acs.jmedchem.3c01682","pmid":"38174919","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09071","title":"Targeted Delivery of Nanoparticle-Conveyed Neutrophils to the Glioblastoma Site for Efficient Therapy.","authors":"Piao, Chunxian; Lee, Jaeho; Kim, Gi Eun; Choe, Young Ho; Lee, Haerang; Hyun, Young-Min","year":2024,"journal":"ACS applied materials & interfaces, 16(32), 41819-41827","doi":"10.1021/acsami.4c05691","pmid":"39057192","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"T7-conjugated cholesterol nanoparticle micelles loaded with temozolomide (TMZ) were efficiently taken up by neutrophils. T7 served a dual purpose: as a cell-penetrating peptide to enhance delivery into neutrophils, and as a transferrin-targeting peptide to direct delivery to tumor cells.\n\nWhen T7/TMZ-conveyed neutrophils were injected intravenously into glioblastoma mouse models, they penetrated the blood-brain barrier and delivered the drug directly to tumor sites. The system demonstrated both efficient drug delivery and therapeutic effects against glioblastoma.","whyItMatters":"Glioblastoma is the most aggressive brain cancer with a median survival of about 15 months. The blood-brain barrier prevents most drugs from reaching the tumor. Using the body's own immune cells as drug carriers, guided by a targeting peptide, is an elegant solution that could dramatically improve treatment delivery for this devastating disease.","specificNumbers":"","methodology":"Researchers synthesized T7-cholesterol nanoparticle micelles that self-assembled in aqueous solution and loaded them with temozolomide. These nanoparticles were attached to neutrophil membranes. In vitro experiments confirmed neutrophil uptake, and in vivo experiments in a glioblastoma mouse model evaluated blood-brain barrier penetration, tumor targeting, and therapeutic efficacy after intravenous injection.","limitations":"This is a preclinical mouse study, and brain tumor models in mice have historically had limited translation to human outcomes. The specific drug delivery efficiency and therapeutic response metrics were not detailed in the abstract. Long-term survival data, potential immune reactions to modified neutrophils, and scalability of neutrophil harvesting and loading were not addressed."},{"rthcId":"RPEP-09072","title":"The first report of leukocytoclastic vasculitis induced by once-weekly subcutaneous semaglutide.","authors":"Pinheiro, Marcelo Maia; de Souza, Luciana Gasques; Nunes, Guilherme Pavini; Martin, Isis Franco; de Oliveira, Yasmin Utuari; Pinheiro, Felipe Moura Maia; Costa, Lygia Nazário; Caprio, Massimiliano; Della-Morte, David; Infante, Marco","year":2024,"journal":"Current medical research and opinion, 40(9), 1525-1531","doi":"10.1080/03007995.2024.2386047","pmid":"39072425","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09073","title":"Bioengineered Nanomedicines Targeting the Intestinal Fc Receptor Achieve the Improved Glucoregulatory Effect of Semaglutide in a Type 2 Diabetic Mice Model.","authors":"Pinto, Soraia; Viegas, Juliana; Cristelo, Cecília; Pacheco, Catarina; Barros, Sofia; Buckley, Stephen T; Garousi, Javad; Gräslund, Torbjörn; Santos, Hélder A; Sarmento, Bruno","year":2024,"journal":"ACS nano, 18(41), 28406-28424","doi":"10.1021/acsnano.4c11172","pmid":"39356547","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09074","title":"Detection of Antimicrobial Proteins/Peptides and Bacterial Proteins Involved in Antimicrobial Resistance in Raw Cow's Milk from Different Breeds.","authors":"Piras, Cristian; De Fazio, Rosario; Di Francesco, Antonella; Oppedisano, Francesca; Spina, Anna Antonella; Cunsolo, Vincenzo; Roncada, Paola; Cramer, Rainer; Britti, Domenico","year":2024,"journal":"Antibiotics (Basel, Switzerland), 13(9)","doi":"10.3390/antibiotics13090838","pmid":"39335011","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Analysis of bovine milk using advanced proteomics revealed:\n\n- Approximately 220 bovine proteins were quantified across breeds\n- Cathelicidins (antimicrobial peptides) and annexins showed higher abundance in intensive-farming breeds compared to Podolica (traditional pasture breeds)\n- Machine learning (LAP-MALDI MS with LDA) could distinguish Podolica milk from other breeds with 98.4% accuracy in the test set\n- Antibiotic resistance proteins (beta-lactamases and tetracycline resistance proteins) were detected in milk from all breeds, with no significant breed-specific differences\n- Metaproteomics revealed diverse microbial ecosystems in milk that varied with environmental factors","whyItMatters":"Understanding the natural antimicrobial peptide content of milk is important for food safety and for identifying new potential antimicrobial compounds. The finding that antibiotic resistance proteins are present in raw milk from all breeds — regardless of farming intensity — has implications for food safety and the spread of antibiotic resistance. Additionally, cathelicidins from milk are studied as potential templates for new anti-infective agents.","specificNumbers":"","methodology":"Milk samples from four bovine breeds (three intensive-farming and one traditional) were analyzed using three complementary approaches: LAP-MALDI mass spectrometry profiling with machine learning classification, bottom-up proteomics (using the Bos taurus database to identify bovine proteins), and metaproteomics (to characterize the microbial community). Antibiotic resistance proteins were identified using the Comprehensive Antibiotic Resistance Database (CARD).","limitations":"The study examined raw (unpasteurized) milk, which is not representative of commercially consumed milk in most countries. Sample sizes per breed are not specified in the abstract. The higher cathelicidin levels in intensive-farming breeds could reflect breed genetics, farming conditions, or subclinical mastitis rather than breed-specific biology. The clinical significance of detecting antibiotic resistance proteins in milk is unclear. The study does not assess the functional antimicrobial activity of the detected peptides."},{"rthcId":"RPEP-09075","title":"Cell-Penetrating Peptides: Promising Therapeutics and Drug-Delivery Systems for Neurodegenerative Diseases.","authors":"Pirhaghi, Mitra; Mamashli, Fatemeh; Moosavi-Movahedi, Faezeh; Arghavani, Payam; Amiri, Ahmad; Davaeil, Bagher; Mohammad-Zaheri, Mahya; Mousavi-Jarrahi, Zahra; Sharma, Deepak; Langel, Ülo; Otzen, Daniel Erik; Saboury, Ali Akbar","year":2024,"journal":"Molecular pharmaceutics, 21(5), 2097-2117","doi":"10.1021/acs.molpharmaceut.3c01167","pmid":"38440998","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09076","title":"The Safety and Efficacy of Peptide Receptor Radionuclide Therapy for Gastro-Entero-Pancreatic Neuroendocrine Tumors: A Single Center Experience.","authors":"Piscopo, Leandra; Zampella, Emilia; Volpe, Fabio; Gaudieri, Valeria; Nappi, Carmela; Di Donna, Erica; Clemente, Stefania; Varallo, Antonio; Scaglione, Mariano; Cuocolo, Alberto; Klain, Michele","year":2024,"journal":"Current oncology (Toronto, Ont.), 31(9), 5617-5629","doi":"10.3390/curroncol31090416","pmid":"39330044","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09077","title":"Melanopsin in the human and chicken choroid.","authors":"Platzl, Christian; Kaser-Eichberger, Alexandra; Trost, Andrea; Strohmaier, Clemens; Stone, Richard; Nickla, Debora; Schroedl, Falk","year":2024,"journal":"Experimental eye research, 247, 110053","doi":"10.1016/j.exer.2024.110053","pmid":"39151779","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09078","title":"Plasma membrane damage limits cytoplasmic delivery by conventional cell penetrating peptides.","authors":"Polderdijk, Stéphanie G I; Limzerwala, Jazeel F; Spiess, Christoph","year":2024,"journal":"PloS one, 19(9), e0305848","doi":"10.1371/journal.pone.0305848","pmid":"39226290","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Using a standardized comparative analysis across cationic, anionic, and amphiphilic cell-penetrating peptides, the researchers demonstrated that intracellular delivery is fundamentally accompanied by irreparable plasma membrane damage as part of the uptake mechanism itself.\n\nThis creates an inescapable correlation: intracellular delivery efficiency scales directly with cell toxicity. The study also showed that CPPs are more efficient at delivering smaller peptides than large molecule cargo, further limiting their pharmaceutical utility.\n\nThe authors conclude that any delivery system based on conventional CPP designs or their underlying principles must accept low delivery yields, because toxicity inherently limits how much cargo can reach the cytoplasm. Novel peptide designs based on deeper understanding of uptake mechanisms are needed to overcome this barrier.","whyItMatters":"Cell-penetrating peptides have been one of the most actively researched drug delivery approaches for decades, with billions invested in trying to get therapeutics inside cells. This study identifies a fundamental mechanistic limitation that explains why progress has been so slow — the delivery mechanism itself is inherently destructive. This finding redirects the field toward developing entirely new peptide designs rather than optimizing existing ones.","specificNumbers":"","methodology":"The researchers conducted a standardized, comparative analysis of multiple previously described cell-penetrating peptides spanning three classes: cationic, anionic, and amphiphilic. They measured delivery efficiency and correlated it with plasma membrane integrity and cell viability to establish the relationship between uptake and membrane damage. Experiments used human cell lines (HeLa cells).","limitations":"The study was conducted entirely in vitro using cell lines, which may not fully reflect how CPPs behave in living organisms where membrane repair mechanisms and tissue context differ. The abstract does not specify how many CPPs were tested or their specific sequences. Results in HeLa cells may not generalize to all cell types. The study focused on conventional CPPs and did not test newer engineered variants that may use different uptake mechanisms."},{"rthcId":"RPEP-09079","title":"Anti‑CGRP monoclonal antibodies in resistant migraine: preliminary real-world effectiveness and clinical predictors of response at two years.","authors":"Pons-Fuster, E; Lozano-Caballero, O; Martín-Balbuena, S; Lucas-Ródenas, C; Mancebo-González, A; De Gorostiza-Frías, I; González-Ponce, C M","year":2024,"journal":"International journal of clinical pharmacy, 46(6), 1317-1326","doi":"10.1007/s11096-024-01758-2","pmid":"38990457","tags":["neuropeptides","pain"],"studyType":"retrospective cohort","evidenceStrength":"moderate","keyFinding":"Anti-CGRP monoclonal antibodies reduced monthly migraine days, disability scores (MIDAS and HIT-6), and acute medication intake over a 24-month period in 120 resistant migraine patients. At 6 and 12 months, 61% and 57% of patients respectively achieved at least 50% reduction in monthly migraine days. Medication overuse at baseline was identified as a significant negative predictor of treatment response (OR 0.23, 95% CI 0.07–0.74, p = 0.014).","whyItMatters":"Most anti-CGRP clinical trials last 3–6 months. This study provides rare 2-year real-world data confirming these peptide-targeting antibodies maintain their effectiveness over time. The finding that medication overuse predicts poor response gives clinicians a practical screening tool before starting expensive biologic therapy.","specificNumbers":"- 120 patients tracked over 24 months\n- 61% were 50% responders at 6 months\n- 57% were 50% responders at 12 months\n- Medication overuse: OR 0.23 (95% CI 0.07-0.74, p = 0.014) for non-response\n- Significant reductions in MIDAS, HIT-6, monthly migraine days, and monthly acute medication use across all time points","methodology":"Single-center retrospective study conducted from December 2019 to June 2023. Patients completed headache diaries tracking monthly migraine days, acute medication intake, and adverse events. Patient-reported outcomes included MIDAS and HIT-6 questionnaires. Responders (≥50% reduction in monthly migraine days) were compared to non-responders using logistic regression.","limitations":"Single-center retrospective design limits generalizability. No control group or placebo comparison. Relatively small sample (120 patients). The study did not compare the three antibodies head-to-head. Patient self-reporting of migraine days introduces recall bias."},{"rthcId":"RPEP-09080","title":"Achievement of normoglycemia with tirzepatide in type 2 diabetes mellitus: A step closer to drug-induced diabetes remission?","authors":"Popovic, Djordje S; Patoulias, Dimitrios; Koufakis, Theocharis; Stavropoulos, Konstantinos; Karakasis, Paschalis; Ruža, Ieva; Papanas, Nikolaos; Rizzo, Manfredi; Doumas, Michael","year":2024,"journal":"Journal of diabetes and its complications, 38(8), 108800","doi":"10.1016/j.jdiacomp.2024.108800","pmid":"38889536","tags":["tirzepatide","diabetes"],"studyType":"meta-analysis","evidenceStrength":"moderate","keyFinding":"Tirzepatide did not just improve blood sugar control. It pushed many patients with type 2 diabetes all the way to normoglycemia, meaning their HbA1c dropped below 5.7%, the threshold where diabetes is no longer diagnosed.\n\nThe odds of achieving this were more than 16 times higher with tirzepatide versus control. This raises the question of whether tirzepatide could enable drug-induced diabetes remission, where blood sugar stays normal even after stopping medication.","whyItMatters":"Most diabetes drugs aim to lower HbA1c to below 7%. Reaching below 5.7% is a different target entirely. It means the patient's blood sugar looks like someone without diabetes. If tirzepatide can reliably produce normoglycemia, it reframes the treatment goal from management to potential remission.","specificNumbers":"- Odds ratio >16 for achieving normoglycemia (HbA1c <5.7%) with tirzepatide vs control\n- Normoglycemia threshold: HbA1c <5.7%","methodology":"The researchers analyzed data from tirzepatide clinical trials in type 2 diabetes. They specifically measured the proportion of patients achieving HbA1c below 5.7% (normoglycemia) on tirzepatide versus control groups. Odds ratios were calculated to quantify the difference.","limitations":"The abstract is brief and does not detail which trials were analyzed, the total sample size, or how long patients maintained normoglycemia. The key question of whether normoglycemia persists after stopping tirzepatide is not addressed. Achieving a lab value below 5.7% during active treatment is not the same as true disease remission."},{"rthcId":"RPEP-09081","title":"Semaglutide and smoking cessation in individuals with type 2 diabetes mellitus: there is no smoke without fire!","authors":"Popovic, Djordje S; Patoulias, Dimitrios; Koufakis, Theocharis; Karakasis, Paschalis; Ruža, Ieva; Papanas, Nikolaos","year":2024,"journal":"Expert review of clinical pharmacology, 17(11), 1009-1012","doi":"10.1080/17512433.2024.2418398","pmid":"39429118","tags":["semaglutide","addiction","glp-1","diabetes"],"studyType":"review/commentary","evidenceStrength":"preliminary","keyFinding":"Among people with type 2 diabetes, semaglutide was linked to a lower risk of medical encounters related to tobacco use disorder compared to other diabetes drug classes. The effect was strongest when comparing semaglutide to insulin. It was weakest compared to other GLP-1 receptor agonists, suggesting the effect may be partly a GLP-1 class effect rather than unique to semaglutide.\n\nSemaglutide users also had fewer prescriptions for smoking cessation medications and less counseling for smoking. These patterns held regardless of whether patients were also obese.","whyItMatters":"About 21% of people with type 2 diabetes smoke, which compounds their already elevated cardiovascular risk. If semaglutide genuinely helps with smoking cessation beyond just weight and glucose control, it could offer a triple benefit: better blood sugar, weight loss, and quitting smoking. GLP-1 receptors exist in brain reward circuits, which provides a plausible mechanism.","specificNumbers":"- 20.8% pooled smoking prevalence among people with type 2 diabetes (from meta-analysis of 3.2 million people across 33 countries)\n- Semaglutide linked to significantly lower risk of medical encounters for tobacco use disorder vs other drug classes\n- Effect strongest vs insulin, weakest vs other GLP-1 receptor agonists\n- Findings consistent regardless of obesity status","methodology":"This was an editorial review summarizing observational data from a large retrospective database study by Wang and colleagues. It compared semaglutide users to matched users of other diabetes drug classes. No randomized controlled trial data on semaglutide and smoking cessation was available at the time of writing.","limitations":"This is an editorial commentary based on observational data, not a clinical trial. The association between semaglutide and reduced tobacco use could reflect confounding factors. People prescribed semaglutide may differ from those on insulin in ways that affect smoking behavior. No randomized evidence confirms that semaglutide directly causes smoking cessation."},{"rthcId":"RPEP-09082","title":"Tirzepatide use and the risk of cancer among individuals with type 2 diabetes mellitus: A meta-analysis of randomized controlled trials.","authors":"Popovic, Djordje S; Patoulias, Dimitrios; Popovic, Lazar S; Karakasis, Paschalis; Papanas, Nikolaos; Mantzoros, Christos S","year":2024,"journal":"Diabetes research and clinical practice, 213, 111758","doi":"10.1016/j.diabres.2024.111758","pmid":"38925294","tags":["tirzepatide","cancer","diabetes","side-effects"],"studyType":"meta-analysis","evidenceStrength":"moderate","keyFinding":"Across all 9 trials, tirzepatide did not increase the risk of cancer overall or any specific cancer type. This held true regardless of what the comparison drug was.\n\nHowever, the authors stress this is preliminary. The trials were short (36 to 72 weeks), which is not long enough to detect most drug-related cancer signals. Cancer takes years to develop, and these studies were designed to measure diabetes outcomes, not cancer risk.","whyItMatters":"Any new widely-prescribed drug needs cancer safety data. Tirzepatide is being used by millions for diabetes and weight loss. Previous GLP-1 drugs raised early concerns about pancreatic and thyroid cancers that were largely not confirmed in longer studies. This meta-analysis provides early reassurance for tirzepatide, though longer follow-up is essential.","specificNumbers":"- 9 randomized controlled trials included\n- Study durations: 36 to 72 weeks\n- No significant increase in risk for any cancer type or overall cancer\n- Small number of total cancer events across all trials (exact count not stated)","methodology":"The researchers conducted a meta-analysis of all available phase 2 and phase 3 randomized controlled trials evaluating tirzepatide in type 2 diabetes, published up to April 2024. They pooled data from 9 trials. The primary endpoint was risk of any cancer. Secondary endpoints covered specific cancer types. Subgroup analyses looked at different comparator drugs.","limitations":"The biggest limitation is time. Cancer typically develops over years, and these trials lasted only 36 to 72 weeks. The number of cancer events was small, reducing statistical power. The trials were not designed to detect cancer as a primary outcome. This is hypothesis-generating, not definitive."},{"rthcId":"RPEP-09083","title":"Evaluation of outcomes of calcitonin gene-related peptide (CGRP)-targeting therapies for acute and preventive migraine treatment based on patient sex.","authors":"Porreca, Frank; Navratilova, Edita; Hirman, Joe; van den Brink, Antoinette Maassen; Lipton, Richard B; Dodick, David W","year":2024,"journal":"Cephalalgia : an international journal of headache, 44(3), 3331024241238153","doi":"10.1177/03331024241238153","pmid":"38477313","tags":["neuropeptides","pain"],"studyType":"subgroup analysis","evidenceStrength":"moderate","keyFinding":"For acute migraine treatment, the three approved gepant drugs produced strong, statistically significant effects in women. The average drug effect for 2-hour pain freedom was 9.5% above placebo in women, with a number needed to treat of 11. In men, the average drug effect was only 2.8% above placebo and did not reach statistical significance. The number needed to treat in men was 36.\n\nFor migraine prevention, the picture was different. CGRP antibodies (erenumab, fremanezumab, galcanezumab, eptinezumab) and the oral preventive atogepant worked in both women and men for episodic migraine. In chronic migraine, the antibodies were similarly effective in both sexes.","whyItMatters":"Migraine affects women 3 times more than men, so most trial participants are women. If gepant drugs do not work as well in men, that is a significant clinical gap. This is one of the first analyses to systematically examine sex-based differences across the entire CGRP drug class.","specificNumbers":"- Women: average 2-hour pain freedom drug effect 9.5% (CI: 7.4-11.6%), NNT = 11\n- Men: average 2-hour pain freedom drug effect 2.8% (CI: -2.5 to 8.2%), NNT = 36\n- Drug effect for women was always numerically greater than for men in every gepant study\n- Preventive antibodies worked in both sexes for episodic and chronic migraine","methodology":"Researchers conducted a subpopulation analysis using published FDA review data for all approved CGRP-targeting migraine drugs. They examined two-hour pain freedom and most bothersome symptom freedom for acute treatments, and change in monthly migraine days for preventive treatments. All data were separated by patient sex.","limitations":"This was a post-hoc subpopulation analysis of FDA data, not a prospective study designed to test sex differences. Men made up a small proportion of trial participants, reducing statistical power. The non-significant results in men could reflect low sample size rather than true lack of efficacy. Individual patient data was not available."},{"rthcId":"RPEP-09084","title":"Diabetes drugs activate neuroprotective pathways in models of neonatal hypoxic-ischemic encephalopathy.","authors":"Poupon-Bejuit, Laura; Geard, Amy; Millicheap, Nathan; Rocha-Ferreira, Eridan; Hagberg, Henrik; Thornton, Claire; Rahim, Ahad A","year":2024,"journal":"EMBO molecular medicine, 16(6), 1284-1309","doi":"10.1038/s44321-024-00079-1","pmid":"38783166","tags":["glp-1","semaglutide","exenatide","neuroprotection"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Both exendin-4 and semaglutide improved outcomes when given right after brain injury in newborn mice. The drugs reduced the size of the damaged brain area, increased survival rates, and improved locomotor function in both short-term and long-term assessments.\n\nThe mechanism involved upregulation of the PI3K/AKT signaling pathway (a cell survival pathway) and increased cAMP levels (a molecule that helps cells communicate). The drugs also reduced inflammation after oxygen-glucose deprivation in brain cells.","whyItMatters":"Hypoxic-ischemic encephalopathy (HIE) happens when a baby's brain does not get enough blood and oxygen during birth. It affects about 1.5 per 1,000 live births worldwide and can cause death or severe brain damage. The only current treatment is cooling the baby's body (therapeutic hypothermia). If GLP-1 drugs could add neuroprotection, it would be a major advance.","specificNumbers":"- Incidence of HIE: 1.5 per 1,000 live births globally\n- Both drugs improved neuropathology scores, survival, and motor function\n- PI3K/AKT pathway upregulated\n- cAMP levels increased\n- Specific effect sizes not reported in abstract","methodology":"Researchers surgically induced hypoxic-ischemic brain injury in 10-day-old mice by blocking the middle cerebral artery. They then gave the mice exendin-4 or semaglutide systemically right after the injury. They measured brain damage using tissue staining, tracked survival, and tested movement abilities. They also studied the mechanism in brain cells deprived of oxygen and glucose in the lab.","limitations":"This was tested in mice, not people. Neonatal mouse brain injury is an imperfect model for human HIE. The drugs were given immediately after injury, which may not reflect realistic clinical timing. No long-term developmental or cognitive outcomes were reported. The leap from preclinical mouse data to neonatal clinical use is enormous."},{"rthcId":"RPEP-09085","title":"Use of Dulaglutide, Semaglutide, and Tirzepatide in Diabetes and Weight Management.","authors":"Powell, Jason; Taylor, James","year":2024,"journal":"Clinical therapeutics, 46(3), 289-292","doi":"10.1016/j.clinthera.2023.12.014","pmid":"38310052","tags":["semaglutide","dulaglutide","tirzepatide","glp-1","regulatory"],"studyType":"review/commentary","evidenceStrength":"preliminary","keyFinding":"Semaglutide outperformed dulaglutide in both HbA1c reduction and weight loss, making it the most sought-after GLP-1 drug. Clinicians began prescribing Ozempic (semaglutide for diabetes) off-label for weight loss, even though Wegovy (semaglutide for weight) existed. This drove shortages.\n\nInsurance companies responded by requiring prior authorizations proving a type 2 diabetes diagnosis before covering these drugs. The commentary notes that most insurance plans still do not cover GLP-1 drugs solely for weight management, pushing weight-loss demand onto the diabetes supply chain.","whyItMatters":"GLP-1 drugs are among the most effective diabetes treatments available. When people with diabetes cannot access them because of demand from weight-loss prescribing, it creates a real clinical problem. This tension between obesity treatment and diabetes management has become one of the biggest access issues in modern medicine.","specificNumbers":"- Semaglutide: FDA-approved for diabetes (Ozempic) and weight loss (Wegovy)\n- Dulaglutide: outperformed by semaglutide in HbA1c and weight reduction\n- Tirzepatide: FDA-approved for diabetes May 2022\n- Insurance now requires prior authorization proving T2DM diagnosis","methodology":"This is a clinical commentary based on published literature and clinical experience. It describes prescribing trends, FDA approval timelines, and insurance coverage issues for dulaglutide, semaglutide, and tirzepatide. No original data analysis was performed.","limitations":"This is a brief commentary, not a systematic study. It does not quantify the extent of shortages or measure patient outcomes from delayed access. The perspectives are from US clinical practice and may not apply globally. The timeline described (2022-2023) is now partially outdated as supply has improved in some areas."},{"rthcId":"RPEP-09086","title":"Real-world experience of galcanezumab in the prevention of migraine in Spain: a systematic literature review.","authors":"Pozo-Rosich, Patricia; García-Azorín, David; Díaz-Cerezo, Silvia; Fernández-Montoya, Julia; de Paz, Héctor David; Núñez, Mercedes","year":2024,"journal":"Frontiers in neurology, 15, 1502475","doi":"10.3389/fneur.2024.1502475","pmid":"39639987","tags":["neuropeptides","pain"],"studyType":"systematic review","evidenceStrength":"moderate","keyFinding":"Across 29 real-world Spanish studies, galcanezumab showed consistent reductions in monthly migraine days and monthly headache days. Disability scores (MIDAS) and headache impact scores (HIT-6) also improved.\n\n12-month persistence ranged from 59.8% to 76.8%, meaning about 6 to 8 out of 10 patients stuck with treatment for a full year. Serious adverse events were rare. One study reported high patient satisfaction. No study included health-related quality of life data.","whyItMatters":"Clinical trials show drugs work under controlled conditions. Real-world data shows how they perform in everyday practice, with typical patients who often have other health conditions, use other medications, and may not be as strictly monitored. This review confirms galcanezumab's benefits translate outside the trial setting in a large Mediterranean population.","specificNumbers":"- 29 publications included\n- 2,592 Spanish adult patients\n- 12-month persistence: 59.8% to 76.8%\n- Significant reductions in monthly migraine days and monthly headache days\n- Improvements in MIDAS disability and HIT-6 impact scores\n- Serious adverse events: rare","methodology":"This was a systematic literature review following PRISMA and Cochrane guidelines. Researchers searched for observational studies on galcanezumab in Spanish patients, published from August 2020 to August 2023, in English or Spanish. They included 29 publications covering 2,592 adult patients.","limitations":"This is a review of observational studies with no control groups or randomization. Publication bias may favor positive results. No study included quality-of-life measures, which limits understanding of the full patient experience. The data is from Spain only and may not generalize to all populations."},{"rthcId":"RPEP-09087","title":"Non-alcoholic fatty liver disease in type 2 diabetes: Emerging evidence of benefit of peroxisome proliferator-activated receptors agonists and incretin-based therapies.","authors":"Pramanik, Subhodip; Pal, Partha; Ray, Sayantan","year":2024,"journal":"World journal of methodology, 14(2), 91319","doi":"10.5662/wjm.v14.i2.91319","pmid":"38983664","tags":["glp-1","semaglutide","tirzepatide","liver","diabetes"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"PPAR agonists work by making cells more sensitive to insulin. Pioglitazone (a PPARγ agonist) and saroglitazar (a PPARα/γ agonist) are recommended by several medical groups for treating fatty liver in diabetes. Newer PPAR drugs like elafibranor and lanifibranor are also showing promise.\n\nGLP-1 receptor agonists take a different approach. They produce significant weight loss and may directly reduce liver inflammation and fibrosis (scarring). The review notes that dual-agonists (like tirzepatide targeting GIP/GLP-1) and triple-agonists have produced even more impressive weight loss, which could further benefit the liver. However, direct evidence of liver benefit from these newer multi-agonists is still limited.","whyItMatters":"NAFLD affects over half of all people with type 2 diabetes, and the combination dramatically increases risk of liver failure, liver cancer, and cardiovascular events. Until resmetirom's recent approval, there was no drug specifically approved for NAFLD. This review shows that existing diabetes drugs may offer liver benefits as a bonus.","specificNumbers":"- More than 50% of people with type 2 diabetes have NAFLD\n- Pioglitazone: recommended by multiple guidelines for NAFLD in diabetes\n- GLP-1 receptor agonists: shown beneficial effects on NAFLD/NASH\n- Dual and triple agonists: impressive weight loss, potential liver benefits under investigation","methodology":"This is a narrative review examining the evidence for PPAR agonists and GLP-1-based therapies in treating NAFLD/NASH in people with type 2 diabetes. It covers both approved drugs and drugs in development, drawing on clinical trial data and mechanistic research.","limitations":"This is a narrative review, not a systematic review or meta-analysis. It does not quantify effect sizes or grade evidence systematically. Long-term safety data for newer PPAR agonists and multi-agonist GLP-1 drugs in liver disease is lacking. Biopsy-proven NASH data is missing for saroglitazar. The review does not address cost or access barriers."},{"rthcId":"RPEP-09088","title":"Incretin mimetics and acute pancreatitis: enemy or innocent bystander?","authors":"Pratley, Richard; Saeed, Zeb I; Casu, Anna","year":2024,"journal":"Current opinion in gastroenterology, 40(5), 404-412","doi":"10.1097/MOG.0000000000001057","pmid":"38967917","tags":["glp-1","side-effects","peptide-safety"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Meta-analyses of long-term randomized controlled trials show DPP-4 inhibitors carry a small increased risk of acute pancreatitis, but GLP-1 receptor agonists and GLP-1/GIP co-agonists do not. GLP-1 receptor agonists and co-agonists are associated with higher rates of cholecystitis and cholelithiasis (gallbladder inflammation and gallstones). No incretin-based drug class is associated with increased pancreatic cancer risk.","whyItMatters":"With GLP-1 drugs now prescribed to millions for diabetes and obesity, safety concerns about pancreatitis have been a persistent worry. This review provides reassurance that GLP-1 receptor agonists themselves don't raise pancreatitis risk, though it flags gallbladder issues as a real concern clinicians should monitor.","specificNumbers":"- DPP-4 inhibitors: small increased risk of acute pancreatitis in meta-analyses\n- GLP-1 receptor agonists: no increased risk of acute pancreatitis\n- GIP/GLP-1 co-agonists: no increased risk of acute pancreatitis\n- GLP-1 drugs and co-agonists: higher rates of cholecystitis and cholelithiasis\n- None of the drug classes linked to pancreatic cancer","methodology":"Narrative review synthesizing evidence from individual randomized controlled trials and meta-analyses of long-term trial data for DPP-4 inhibitors, GLP-1 receptor agonists, and GLP-1/GIP co-agonists.","limitations":"Narrative review without systematic methodology. Individual trials were often underpowered to detect rare events like pancreatitis. Observational data on gallbladder risk may be confounded by weight loss itself, which is a known gallstone risk factor."},{"rthcId":"RPEP-09089","title":"Effects of Semaglutide on Heart Failure Outcomes in Diabetes and Chronic Kidney Disease in the FLOW Trial.","authors":"Pratley, Richard E; Tuttle, Katherine R; Rossing, Peter; Rasmussen, Søren; Perkovic, Vlado; Nielsen, Olav Wendelboe; Mann, Johannes F E; MacIsaac, Richard J; Kosiborod, Mikhail N; Kamenov, Zdravko; Idorn, Thomas; Hansen, Marco Bo; Hadjadj, Samy; Bakris, George; Baeres, Florian M M; Mahaffey, Kenneth W","year":2024,"journal":"Journal of the American College of Cardiology, 84(17), 1615-1628","doi":"10.1016/j.jacc.2024.08.004","pmid":"39217553","tags":["semaglutide","cardiovascular","kidney","diabetes","glp-1"],"studyType":"randomized controlled trial","evidenceStrength":"strong","keyFinding":"Semaglutide reduced the composite outcome of heart failure events or cardiovascular death (HR 0.73, meaning a 27% reduction, p = 0.0005). When broken down, it reduced heart failure events alone by 27% (HR 0.73, p = 0.0068) and cardiovascular death alone by 29% (HR 0.71, p = 0.0036).\n\nAbout 19% of participants had heart failure at baseline. The benefit was consistent in both groups: those with pre-existing heart failure (HR 0.73, p = 0.034) and those without (HR 0.72, p = 0.003). Patients with more severe heart failure (NYHA class III) and reduced ejection fraction had higher overall event rates regardless of treatment.","whyItMatters":"People with both type 2 diabetes and chronic kidney disease have extremely high rates of heart failure and cardiovascular death. This is one of the highest-risk populations in medicine. Showing that semaglutide reduces heart failure events in this group is significant because treatment options for this population are limited and outcomes are poor.","specificNumbers":"- 3,533 participants randomized\n- Median follow-up: 3.4 years\n- HF events or CV death: HR 0.73 (95% CI 0.62-0.87, p = 0.0005)\n- HF events alone: HR 0.73 (95% CI 0.58-0.92, p = 0.0068)\n- CV death alone: HR 0.71 (95% CI 0.56-0.89, p = 0.0036)\n- ~19% had heart failure at baseline\n- Primary kidney outcome: 24% reduction (previously reported)","methodology":"This was a prespecified analysis from the FLOW trial, a randomized, double-blind, placebo-controlled trial. 3,533 participants with type 2 diabetes and chronic kidney disease were randomized 1:1 to weekly subcutaneous semaglutide 1 mg or placebo. The primary trial had already shown a 24% reduction in the main kidney composite outcome. Median follow-up was 3.4 years. Heart failure events and cardiovascular death were adjudicated by an independent committee.","limitations":"This was a prespecified secondary analysis, not the primary endpoint of the FLOW trial. Heart failure data was collected by investigators, not through a central core lab. The population was specific (T2D plus CKD), so results may not apply to people with heart failure but without kidney disease. The NYHA class III and HFrEF subgroups had too few patients for definitive subgroup conclusions."},{"rthcId":"RPEP-09090","title":"Antidiabetic Treatment and Prevention of Ischemic Stroke: A Systematic Review.","authors":"Prentza, Vasiliki; Pavlidis, George; Ikonomidis, Ignatios; Pililis, Sotirios; Lampsas, Stamatios; Kountouri, Aikaterini; Pliouta, Loukia; Korakas, Emmanouil; Thymis, John; Palaiodimou, Lina; Tsegka, Aikaterini; Markakis, Konstantinos; Halvatsiotis, Panagiotis; Tsivgoulis, Georgios; Lambadiari, Vaia","year":2024,"journal":"Journal of clinical medicine, 13(19)","doi":"10.3390/jcm13195786","pmid":"39407846","tags":["glp-1","semaglutide","dulaglutide","cardiovascular","diabetes"],"studyType":"systematic review","evidenceStrength":"moderate","keyFinding":"Among diabetes medications studied for stroke prevention, GLP-1 receptor agonists (specifically semaglutide and dulaglutide) reduced the risk of ischemic stroke in people with type 2 diabetes. Pioglitazone significantly reduced recurrent stroke risk. DPP-4 inhibitors, SGLT2 inhibitors, and insulin did not affect stroke incidence. Metformin monotherapy showed possible stroke reduction but evidence was less definitive.","whyItMatters":"People with diabetes have a 20% higher stroke risk than the general population. Knowing which diabetes drugs also protect against stroke helps clinicians choose treatments that address both blood sugar and cardiovascular risk simultaneously.","specificNumbers":"- 32 studies included in the review\n- Diabetes increases ischemic stroke risk by 20%\n- Pioglitazone: significant reduction in recurrent stroke\n- Semaglutide and dulaglutide: reduced primary stroke risk\n- DPP-4 inhibitors, SGLT2 inhibitors, insulin: no stroke benefit detected","methodology":"Systematic review searching PubMed, Cochrane, and Scopus databases. Included 32 studies examining clinical benefits of various antidiabetic therapies for ischemic stroke prevention in diabetic populations.","limitations":"Systematic review without meta-analysis, so no pooled effect sizes are reported. Heterogeneity across included studies in design, populations, and follow-up periods. Does not distinguish between different stroke subtypes. No data on newer dual GIP/GLP-1 agonists like tirzepatide."},{"rthcId":"RPEP-09091","title":"SGLT2 Inhibitors, but Not GLP-1 Receptor Agonists, Reduce Incidence of Gout in People Living With Type 2 Diabetes Across the Therapeutic Spectrum.","authors":"Preston, Frank G; Anson, Matthew; Riley, David R; Ibarburu, Gema H; Henney, Alexander; Lip, Gregory Y H; Cuthbertson, Daniel J; Alam, Uazman; Zhao, Sizheng S","year":2024,"journal":"Clinical therapeutics, 46(11), 835-840","doi":"10.1016/j.clinthera.2024.06.021","pmid":"39068059","tags":["glp-1","diabetes","bone-joint","side-effects"],"studyType":"cohort study","evidenceStrength":"moderate","keyFinding":"SGLT2 inhibitors with metformin reduced gout incidence by 25% compared to metformin alone (HR 0.75, p < 0.0001). SGLT2 inhibitors with insulin reduced gout by 17% versus insulin alone (HR 0.83, p < 0.0001).\n\nGLP-1 receptor agonists showed no significant difference in gout incidence versus either metformin or insulin controls.\n\nWhen SGLT2 inhibitors were compared directly to GLP-1 drugs, they had lower gout rates in both the metformin group (HR 0.77, p < 0.0001) and the insulin group (HR 0.82, p < 0.0001).","whyItMatters":"Gout is common in type 2 diabetes. SGLT2 inhibitors lower uric acid levels (the chemical that causes gout) as part of how they work. This study provides large-scale real-world evidence that this biochemical effect translates to fewer actual gout episodes. For patients with both diabetes and gout risk, this could tip the scale toward SGLT2 inhibitors.","specificNumbers":"- Metformin control: 1,111,449 patients\n- SGLT2i + metformin: 101,706 patients\n- GLP-1 + metformin: 110,180 patients\n- Insulin control: 1,398,066 patients\n- SGLT2i + metformin vs metformin: HR 0.75 (95% CI 0.69-0.82, p < 0.0001)\n- SGLT2i + insulin vs insulin: HR 0.83 (95% CI 0.74-0.92, p < 0.0001)\n- SGLT2i vs GLP-1 (metformin users): HR 0.77 (p < 0.0001)\n- SGLT2i vs GLP-1 (insulin users): HR 0.82 (p < 0.0001)","methodology":"Researchers conducted a cohort study using the TriNetX federated database, an international electronic health records network. They included patients started on metformin or insulin, with or without an SGLT2 inhibitor or GLP-1 drug, at least 2 years before the analysis date. Groups were propensity score matched (1:1) for 26 characteristics. They tracked gout, all-cause mortality (positive control), and herpes zoster (negative control) over 5 years.","limitations":"This is an observational database study with propensity score matching, not a randomized trial. Residual confounding is possible despite matching for 26 variables. Gout diagnosis in electronic health records may be inconsistent. The TriNetX database may not represent all populations equally. The study compared drug additions rather than head-to-head monotherapy."},{"rthcId":"RPEP-09092","title":"POSEIDON: Peptidic Objects SEquence-based Interaction with cellular DOmaiNs: a new database and predictor.","authors":"Preto, António J; Caniceiro, Ana B; Duarte, Francisco; Fernandes, Hugo; Ferreira, Lino; Mourão, Joana; Moreira, Irina S","year":2024,"journal":"Journal of cheminformatics, 16(1), 18","doi":"10.1186/s13321-024-00810-7","pmid":"38365724","tags":["cell-penetrating","peptide-design","peptide-delivery"],"studyType":"computational/database","evidenceStrength":"moderate","keyFinding":"The POSEIDON database contains over 2,300 experimental entries with quantitative uptake values (how much peptide actually entered cells) and physicochemical properties for 1,315 peptides. Using this data plus genomic features of different cell lines, the team trained a regression model.\n\nThe model achieved a Pearson correlation of 0.87, Spearman correlation of 0.88, and r-squared of 0.76 on an independent test set. This means the model explains about 76% of the variation in peptide uptake across different cell types.","whyItMatters":"Getting drugs inside cells is one of the biggest challenges in medicine. Cell-penetrating peptides are a promising solution, but designing the right peptide for the right cell type has been largely trial and error. A tool that predicts uptake before any lab work could dramatically speed up drug delivery research.","specificNumbers":"- 2,300+ experimental entries in the database\n- 1,315 peptides with physicochemical profiles\n- 1,200+ entries used for model training\n- Pearson correlation: 0.87\n- Spearman correlation: 0.88\n- r² score: 0.76 on independent test set","methodology":"Researchers curated a database from published experiments, standardizing uptake measurements across different studies. They then used over 1,200 entries with both peptide features and cell line genomic data to train a machine learning regression model. They validated it on an independent test set that the model had never seen during training.","limitations":"The database, while the largest of its kind, contains 2,300 entries from published literature, which may not cover all peptide types or cell types equally. Lab-to-lab variability in uptake measurements could introduce noise. The model was validated on held-out data but not prospectively tested in new experiments. Predicted uptake in cell culture may not translate to uptake in living organisms."},{"rthcId":"RPEP-09093","title":"Neuro- and vasoprotective potential of neuropeptide Y Y2 receptor agonist, NPY13-36, against transient focal cerebral ischemia in spontaneously hypertensive rats.","authors":"Przykaza, Łukasz; Domin, Helena; Śmiałowska, Maria; Stanaszek, Luiza; Boguszewski, Paweł M; Kozniewska, Ewa","year":2024,"journal":"Neuroscience, 562, 10-23","doi":"10.1016/j.neuroscience.2024.10.035","pmid":"39433082","tags":["neuropeptides","neuroprotection"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"NPY13-36 was injected directly into the brain during either the ischemic phase (while blood flow was blocked) or the reperfusion phase (when blood flow returned). The drug was effective when given during reperfusion, not during ischemia.\n\nDuring reperfusion, NPY13-36 reduced infarct size (the dead brain area), improved gait, mobility, and sensorimotor function, and restored normal microcirculatory response to nitric oxide synthase blockade. The vasoprotective effect was a new discovery, meaning the drug protected the tiny blood vessels in the brain, not just the neurons.","whyItMatters":"Most stroke neuroprotection research uses healthy young animals, which poorly represents human stroke patients who typically have high blood pressure and other conditions. This study used hypertensive rats, making it more clinically relevant. The discovery of vasoprotection (blood vessel protection) in addition to neuroprotection is a new mechanism that could be important for stroke treatment.","specificNumbers":"- Dose: 10 μg NPY13-36 in 6 μL saline, given into brain ventricles\n- Ischemia duration: 90 minutes of middle cerebral artery occlusion\n- Drug was effective during reperfusion but not during ischemia\n- Reduced infarct area\n- Improved gait, mobility, and sensorimotor scores\n- Restored microvascular response to NO synthase blockade","methodology":"Researchers used spontaneously hypertensive rats (SHR), which naturally develop high blood pressure. They blocked the middle cerebral artery for 90 minutes to cause stroke, then allowed blood to return. NPY13-36 (10 micrograms in 6 microliters saline) was injected into the brain ventricles during either ischemia or reperfusion. Brain blood flow was monitored with laser-Doppler. Outcomes included infarct size (TTC staining), behavioral tests, and microvascular responses.","limitations":"This was tested in rats, not people. The drug was injected directly into the brain, which is not a practical delivery method for human patients. The sample size is not stated in the abstract. Spontaneously hypertensive rats, while better than healthy rats, still do not fully replicate human stroke. The drug had to be given very shortly after reperfusion, which may not be achievable clinically."},{"rthcId":"RPEP-09094","title":"Evaluating remission of type 2 diabetes using a metabolic intervention including fixed-ratio insulin degludec and liraglutide: A randomized controlled trial.","authors":"Punthakee, Zubin; Hall, Stephanie; McInnes, Natalia; Sherifali, Diana; Tsiplova, Kate; Kirabo, Faith R; Ransom, Thomas P P; Harris, Stewart B; Lochnan, Heather A; Sigal, Ronald J; Ghosh, Mahua; Spaic, Tamara; Gerstein, Hertzel C","year":2024,"journal":"Diabetes, obesity & metabolism, 26(12), 5600-5608","doi":"10.1111/dom.15926","pmid":"39239702","tags":["liraglutide","diabetes","glp-1"],"studyType":"randomized controlled trial","evidenceStrength":"strong","keyFinding":"During the 16-week intervention, participants achieved significantly lower HbA1c (40 vs 51 mmol/mol, p < 0.0001) and lost more weight (3.3% vs 1.9%, p = 0.02) compared to controls.\n\nAfter stopping all glucose-lowering drugs, there was a 37% lower hazard of diabetes relapse in the intervention group (HR 0.63, 95% CI 0.45-0.88, p = 0.007). However, this benefit did not last. At 12 weeks post-intervention, remission rates were 17.7% vs 12.5% (not significant). At 52 weeks, they were 6.3% vs 3.8% (not significant).\n\nThe key takeaway: intensive metabolic intervention delayed relapse but could not sustain remission once drugs were stopped.","whyItMatters":"Type 2 diabetes remission is a hot topic. Some studies show intensive weight loss can put diabetes into remission. This trial tested whether adding a powerful GLP-1/insulin combination to lifestyle changes could boost remission rates. The disappointing result, where remission did not last, suggests that more than 16 weeks of intervention may be needed, or that the weight loss achieved (3.3%) was too modest.","specificNumbers":"- 159 participants randomized (79 intervention, 80 control)\n- Age: 57 ± 10 years\n- Diabetes duration: 2.6 ± 1.5 years\n- BMI: 33.5 ± 6.5 kg/m²\n- Baseline HbA1c: 53 ± 7 mmol/mol\n- Post-intervention HbA1c: 40 vs 51 mmol/mol (p < 0.0001)\n- Weight loss: 3.3% vs 1.9% (p = 0.02)\n- Hazard of relapse: HR 0.63 (95% CI 0.45-0.88, p = 0.007)\n- 52-week remission: 6.3% vs 3.8% (not significant)","methodology":"This was a multicenter, open-label randomized controlled trial. 159 insulin-naive participants within 5 years of type 2 diabetes diagnosis were randomized to a 16-week intensive intervention (dietary coaching, exercise coaching, diabetes management coaching, metformin, and fixed-ratio insulin degludec/liraglutide) or standard care. After the intervention period, all glucose-lowering drugs were stopped, and patients were followed for one year for diabetes relapse and sustained remission.","limitations":"The trial was open-label, meaning both patients and doctors knew who received the intervention, which could bias results. The weight loss achieved (3.3%) was modest compared to trials that successfully achieved remission. The 16-week intervention period may have been too short. The sample size (159) limited power to detect small remission rate differences. The insulin degludec/liraglutide combination may have suppressed HbA1c pharmacologically without changing the underlying disease."},{"rthcId":"RPEP-09095","title":"Unlocking New Therapeutic Options for Vincristine-Induced Neuropathic Pain: The Impact of Preclinical Research.","authors":"Pușcașu, Ciprian; Negreș, Simona; Zbârcea, Cristina Elena; Chiriță, Cornel","year":2024,"journal":"Life (Basel, Switzerland), 14(11)","doi":"10.3390/life14111500","pmid":"39598298","tags":["liraglutide","oxytocin","neuroprotection","pain","glp-1"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Among the novel agents studied in animal models, liraglutide showed neuroprotective and anti-inflammatory effects against vincristine-induced nerve damage. Oxytocin demonstrated analgesic properties. Other promising candidates included ulinastatin (enzyme inhibitor), aripiprazole (antipsychotic), anakinra (IL-1 receptor antagonist), and thioctic acid (antioxidant). All work through different mechanisms including reducing inflammation, protecting nerve integrity, and modulating pain pathways.","whyItMatters":"Most patients receiving cumulative vincristine doses above 4 mg/m² develop neuropathy, often forcing dose reductions or treatment discontinuation. Currently there are few effective treatments. Identifying peptide-based neuroprotectants could preserve both nerve function and cancer treatment efficacy.","specificNumbers":"- Most patients with cumulative vincristine dose >4 mg/m² develop neuropathy\n- Liraglutide: neuroprotective and anti-inflammatory in animal models\n- Oxytocin: analgesic effects in animal models\n- Thioctic acid: antioxidant nerve protection in animal models","methodology":"Narrative review consolidating preclinical (animal model) studies from the past decade on pharmacological interventions for vincristine-induced peripheral neuropathy. Focuses on mechanism of action and analgesic efficacy in rodent models.","limitations":"All findings are from animal models — no human clinical trial data exists for these agents in chemotherapy-induced neuropathy. Animal models of neuropathic pain may not fully replicate human experience. The review is narrative rather than systematic, introducing potential selection bias in which studies were included."},{"rthcId":"RPEP-09096","title":"Behaviour Hallmarks in Alzheimer's Disease 5xFAD Mouse Model.","authors":"Pádua, Mafalda Soares; Guil-Guerrero, José L; Lopes, Paula Alexandra","year":2024,"journal":"International journal of molecular sciences, 25(12)","doi":"10.3390/ijms25126766","pmid":"38928472","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09097","title":"Combined Use of GDF-15 and NT-Pro BNP for Outcome Prediction in Patients with Acute Heart Failure.","authors":"Płonka, Joanna; Klus, Anna; Wężyk, Natalia; Dąbrowska, Klaudia; Rzepiela, Lidia; Gawrylak-Dryja, Ewa; Nalewajko, Krzysztof; Feusette, Piotr; Gierlotka, Marek","year":2024,"journal":"Journal of clinical medicine, 13(19)","doi":"10.3390/jcm13195936","pmid":"39407996","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The primary endpoint (death or heart failure rehospitalization at 1 year) occurred in 31 of 104 patients. Optimal GDF-15 cut-offs were 5115.5 pg/mL (admission), 4145 pg/mL (discharge), and 4218.5 pg/mL (30 days). NT-proBNP cut-offs were 6011 ng/L, 1250 ng/L, and 1456.5 ng/L at the same timepoints. Patients with both markers above cut-off had the highest risk at all three timepoints. The combined 30-day model achieved the best prediction (AUC 0.75) for the composite endpoint, outperforming single biomarker measurements.","whyItMatters":"NT-proBNP is already the standard heart failure biomarker, but it captures only one aspect of the disease — cardiac wall stress. By adding GDF-15 (reflecting inflammation, metabolic stress, and fibrosis), clinicians get a more complete picture. The serial measurement approach — tracking both biomarkers over time rather than relying on a single snapshot — better captures the dynamic nature of heart failure and identifies patients whose risk remains elevated after initial treatment.","specificNumbers":"","methodology":"Prospective observational study of 104 consecutive acute heart failure patients (mean age 65 years). Blood samples for NT-proBNP and GDF-15 were collected at admission, discharge, and 30-day follow-up. ROC analysis determined optimal cut-off values. The primary composite endpoint was all-cause mortality or heart failure rehospitalization at 1-year follow-up.","limitations":"Small single-center study with only 104 patients, limiting statistical power and generalizability. The composite endpoint included both mortality and rehospitalization, which have different clinical implications. The AUC of 0.75, while reasonable, is moderate — suggesting room for improvement. GDF-15 is not yet routinely available in all clinical laboratories. The study did not validate findings in an independent cohort."},{"rthcId":"RPEP-09098","title":"Setmelanotide: A Melanocortin-4 Receptor Agonist for the Treatment of Severe Obesity Due to Hypothalamic Dysfunction.","authors":"Qamar, Sulmaaz; Mallik, Ritwika; Makaronidis, Janine","year":2024,"journal":"TouchREVIEWS in endocrinology, 20(2), 62-71","doi":"10.17925/EE.2024.20.2.9","pmid":"39526054","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09099","title":"Adipocyte inflammation is the primary driver of hepatic insulin resistance in a human iPSC-based microphysiological system.","authors":"Qi, Lin; Groeger, Marko; Sharma, Aditi; Goswami, Ishan; Chen, Erzhen; Zhong, Fenmiao; Ram, Apsara; Healy, Kevin; Hsiao, Edward C; Willenbring, Holger; Stahl, Andreas","year":2024,"journal":"Nature communications, 15(1), 7991","doi":"10.1038/s41467-024-52258-w","pmid":"39266553","tags":["semaglutide","glp-1","liver","inflammation"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"The researchers created a microphysiological system (MPS), a tiny interconnected network of human fat cells, liver cells, and inflammatory immune cells (macrophages). When macrophages inflamed the fat cells, the liver cells accumulated fat and stopped responding to insulin properly. This recreated the early stages of metabolic dysfunction-associated steatotic liver disease (MASLD, previously called NAFLD).\n\nSemaglutide improved liver cell function in this system. The key discovery: semaglutide acted on the fat cells, not the liver cells. By calming the inflamed fat cells, semaglutide indirectly reduced liver fat accumulation and restored insulin sensitivity throughout the system.","whyItMatters":"One of the biggest questions about semaglutide's liver benefits has been whether the drug acts directly on the liver or indirectly through weight loss and fat tissue changes. This study provides evidence for the indirect route. Semaglutide appears to fix the liver by fixing the fat cells first. This is important for understanding how GLP-1 drugs work and for developing better treatments.","specificNumbers":"- All cells derived from a single human induced pluripotent stem cell line (isogenic)\n- Macrophage-induced fat cell inflammation caused liver fat accumulation and insulin resistance\n- Semaglutide acted specifically on adipocytes (fat cells), not hepatocytes (liver cells)\n- System-wide insulin resistance was reversed","methodology":"Researchers generated white adipocytes (fat cells), hepatocytes (liver cells), and proinflammatory macrophages (immune cells) from a single human induced pluripotent stem cell line. These were connected in a microphysiological system (organ-on-chip platform). They tested different fat-to-liver cell ratios and inflammatory conditions. Semaglutide and other drugs were tested for their effects on the system.","limitations":"This is an in vitro (lab dish) study, not an animal or human study. Organ-on-chip models are simplified representations of human biology that lack blood flow, nervous system input, and the full complexity of organ crosstalk. The cells were derived from one stem cell line, which may not represent all genetic backgrounds. Results may not translate to actual human patients."},{"rthcId":"RPEP-09100","title":"Site-Specific Stability Evaluation of Antibody-Drug Conjugate in Serum Using a Validated Liquid Chromatography-Mass Spectrometry Method.","authors":"Qi, Meiling; Zhu, Chenyue; Chen, Yi; Wang, Chenxi; Ye, Xinyuan; Li, Sen; Cheng, Zhongzhe; Jiang, Hongliang; Du, Zhifeng","year":2024,"journal":"Journal of proteome research, 23(11), 5131-5142","doi":"10.1021/acs.jproteome.4c00631","pmid":"39363186","tags":["peptide-design","cancer"],"studyType":"method development","evidenceStrength":"moderate","keyFinding":"Using ado-trastuzumab emtansine (T-DM1, a breast cancer ADC) as the test drug, researchers identified conjugated peptides (the spots where the toxic drug attaches to the antibody) using a proteomics approach. They then built a semi-quantitative measurement method using liquid chromatography-mass spectrometry.\n\nAfter optimizing sample preparation to reduce blood serum interference, they validated the method and applied it to measure stability at different conjugation sites on T-DM1. The results showed clear differences in stability between sites. Some attachment points lost their drug payload faster than others in serum.","whyItMatters":"ADC stability is critical. If the toxic drug detaches from the antibody too early (in the bloodstream rather than at the tumor), it causes side effects without killing cancer cells. Knowing which attachment sites are stable and which are not can guide the design of better ADCs with fewer side effects.","specificNumbers":"- Model drug: ado-trastuzumab emtansine (T-DM1)\n- Method: LC-QTRAP-MS/MS\n- First study to assess site-specific conjugation stability in serum\n- Different conjugation sites showed different stability profiles","methodology":"Researchers first identified conjugated peptides on T-DM1 using proteomic analysis. They developed a semi-quantitative method using LC-QTRAP-MS/MS (liquid chromatography coupled to a hybrid mass spectrometer). They optimized serum sample preparation to reduce matrix interference. The method was validated for precision, accuracy, and sensitivity, then applied to measure site-specific stability in serum over time.","limitations":"This is a method development study, not a clinical study. It was tested with one ADC (T-DM1) and needs validation with other ADCs. The method is semi-quantitative, not fully quantitative. Serum stability in a test tube may not perfectly predict behavior in a patient's body. The approach requires specialized mass spectrometry equipment not available in all labs."},{"rthcId":"RPEP-09101","title":"Probiotics suppress LL37 generated rosacea-like skin inflammation by modulating the TLR2/MyD88/NF-κB signaling pathway.","authors":"Qi, Xinyue; Xiao, Yiran; Zhang, Xinfeng; Zhu, Zhenlin; Zhang, Hongyan; Wei, Jing; Zhao, Zhixiang; Li, Ji; Chen, Tingtao","year":2024,"journal":"Food & function, 15(17), 8916-8934","doi":"10.1039/d4fo03083d","pmid":"39143863","tags":["ll-37","antimicrobial-peptides","inflammation","gut-healing"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Both L. salivarius 23-006 and L. paracasei 23-008 reduced skin lesions, skin inflammatory infiltrates, and inflammatory factor expression in the LL-37 rosacea mouse model. The combination of both strains produced the strongest effects.\n\nThe probiotics worked by inhibiting the TLR2/MyD88/NF-kB signaling pathway, which is the same pathway LL-37 uses to trigger rosacea inflammation. They also reduced cathelicidin LL-37 expression itself, breaking the cycle. Gut microbiome analysis showed the probiotics increased Lactobacillus levels while reducing Coprococcus and Oscillospira, and strengthened the intestinal barrier.\n\nPostbiotics (the metabolic byproducts of the bacteria, used without live bacteria) also helped but were less effective than live probiotic treatment.","whyItMatters":"Rosacea affects roughly 5% of the global population and is difficult to treat. LL-37 (cathelicidin) is overexpressed in rosacea skin and drives inflammation. The gut-skin axis is an emerging concept suggesting that gut bacteria influence skin conditions. This study provides a mechanistic link between probiotic gut treatment and skin improvement in a rosacea model.","specificNumbers":"- Two strains tested: L. salivarius 23-006 and L. paracasei 23-008\n- Combination treatment was most effective\n- TLR2/MyD88/NF-kB pathway was inhibited\n- LL-37 expression reduced in treated mice\n- Lactobacillus abundance increased; Coprococcus and Oscillospira decreased\n- Postbiotics were less effective than live probiotics","methodology":"Researchers isolated L. salivarius 23-006 and L. paracasei 23-008 from healthy human volunteer feces. They created rosacea-like skin inflammation in mice by injecting LL-37 peptide. Mice were treated with individual probiotics, the combination, or postbiotics. They measured skin inflammation, inflammatory markers, LL-37 expression, TLR2/MyD88/NF-kB pathway activity, and gut microbiome composition via 16S rRNA sequencing.","limitations":"This was tested in mice, not people. The LL-37 injection model creates rosacea-like symptoms but is not the same as human rosacea, which develops over years. The probiotic strains were from healthy volunteers and may not work the same in rosacea patients. The gut-to-skin mechanism is demonstrated in mice but not confirmed in humans. Postbiotics were less effective, which limits the shelf-stable product potential."},{"rthcId":"RPEP-09102","title":"Rational fusion design inspired by cell-penetrating peptide: SS31/S-14 G Humanin hybrid peptide with amplified multimodal efficacy and bio-permeability for the treatment of Alzheimer's disease.","authors":"Qian, Kang; Yang, Peng; Li, Yixian; Meng, Ran; Cheng, Yunlong; Zhou, Lingling; Wu, Jing; Xu, Shuting; Bao, Xiaoyan; Guo, Qian; Wang, Pengzhen; Xu, Minjun; Sheng, Dongyu; Zhang, Qizhi","year":2024,"journal":"Asian journal of pharmaceutical sciences, 19(4), 100938","doi":"10.1016/j.ajps.2024.100938","pmid":"39253611","tags":["cell-penetrating","neuroprotection","peptide-design","bioavailability"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"HNSS showed a 2-fold improvement in brain distribution compared to HNG alone. Its structure mimics cell-penetrating peptides, which explains the enhanced brain entry.\n\nInside the brain, HNSS worked on multiple fronts. It targeted mitochondria and scavenged reactive oxygen species (damaging molecules). It activated the STAT3 pathway, which helps cell survival. It also blocked amyloid beta from clumping into the toxic oligomers and fibrils that characterize Alzheimer's. HNSS reduced amyloid deposits in neurons and helped immune cells in the brain (microglia) clear amyloid.\n\nIn 3xTg-AD transgenic mice (a standard Alzheimer's model), HNSS treatment prevented brain neuron loss and improved cognitive performance on memory tests.","whyItMatters":"Getting peptide drugs into the brain is one of the biggest challenges in neurodegenerative disease research. Most peptides cannot cross the blood-brain barrier. By designing a hybrid that naturally mimics cell-penetrating peptides, the researchers found a way to double brain entry without needing a separate delivery vehicle. The multi-target approach is also important because Alzheimer's involves many interconnected mechanisms.","specificNumbers":"- 2-fold improvement in brain distribution over HNG\n- Reduced ROS (reactive oxygen species)\n- Activated p-STAT3 pathway\n- Inhibited Aβ oligomerization and fibrillation\n- Promoted microglial phagocytosis of Aβ\n- Prevented neuron loss in 3xTg-AD mice\n- Improved cognitive performance in memory tests","methodology":"Researchers designed the HNSS hybrid peptide by fusing SS31 (a mitochondria-targeting peptide) with S-14 G Humanin (a neuroprotective peptide). They tested brain permeability, mitochondrial function, amyloid beta aggregation, and neuron-microglia interactions in cell cultures. In vivo testing used 3xTg-AD transgenic Alzheimer's mice.","limitations":"This was tested in mice, not people. The 3xTg-AD mouse model overexpresses human Alzheimer's genes and does not perfectly mimic human disease progression. Brain distribution was improved 2-fold but absolute brain levels were not reported. Long-term safety, dosing, and manufacturing scalability are unknown. Many Alzheimer's treatments that work in mice have failed in human trials."},{"rthcId":"RPEP-09103","title":"Intermittent Fasting Targets Osteocyte Neuropeptide Y to Relieve Osteoarthritis.","authors":"Qian, Yu-Xuan; Rao, Shan-Shan; Tan, Yi-Juan; Wang, Zun; Yin, Hao; Wan, Teng-Fei; He, Ze-Hui; Wang, Xin; Hong, Chun-Gu; Zeng, Hai-Jin; Luo, Yi; Duan, Yan-Xin; Zhu, Hao; Hu, Xin-Yue; Zou, Ling; Zhang, Yan; Liu, Bing-Bing; Wang, Zhen-Xing; Du, Wei; Chen, Chun-Yuan; Xie, Hui","year":2024,"journal":"Advanced science (Weinheim, Baden-Wurttemberg, Germany), 11(34), e2400196","doi":"10.1002/advs.202400196","pmid":"38978353","tags":["neuropeptides","bone-joint","inflammation"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Osteocytes (the most common bone cells) secreted excess neuropeptide Y during osteoarthritis. This NPY promoted inflammation, osteoclast formation (cells that break down bone), and neurite outgrowth (nerve growth that contributes to pain).\n\nIntermittent fasting reversed these effects. Culture medium from osteocytes of fasting mice did not trigger the same inflammatory and bone-destroying responses. When researchers genetically deleted NPY from osteocytes, intermittent fasting lost its beneficial effects on osteoarthritis. This proved that osteocyte NPY is the specific target through which fasting works.\n\nThe findings held in both surgically induced osteoarthritis (meniscus destabilization) and natural aging-induced osteoarthritis.","whyItMatters":"Osteoarthritis affects over 500 million people worldwide with no disease-modifying treatment. Intermittent fasting has shown health benefits in many contexts, but the mechanism for joint protection was unknown. This study identifies a specific molecular pathway: osteocyte NPY. This could lead to targeted drug development for osteoarthritis.","specificNumbers":"- Excess NPY secreted by osteocytes during osteoarthritis\n- NPY promoted pro-inflammatory, pro-osteoclastic, and pro-neurite outgrowth effects\n- Intermittent fasting reversed these effects\n- Osteocyte NPY knockout abolished fasting benefits\n- Effective in both surgical (DMM) and aging-induced OA models","methodology":"Researchers used two mouse osteoarthritis models: surgically induced (destabilization of the medial meniscus, DMM) and natural aging. They tested intermittent fasting in both models. They measured NPY levels, inflammation markers, osteoclast formation, and nerve outgrowth. They used osteocyte-specific NPY knockout mice to confirm the mechanism. Cell culture experiments with osteocyte-conditioned medium tested the direct effects of NPY.","limitations":"This was tested in mice, not people. Mouse osteoarthritis models do not perfectly replicate the decades-long progression of human osteoarthritis. The specific intermittent fasting protocol may not translate directly to human practice. The osteocyte NPY knockout was a genetic deletion, not a drug intervention. Whether blocking NPY pharmacologically would have the same effect is unknown."},{"rthcId":"RPEP-09104","title":"Efficacy and safety of once-weekly tirzepatide for weight management compared to placebo: An updated systematic review and meta-analysis including the latest SURMOUNT-2 trial.","authors":"Qin, Wenhui; Yang, Jun; Ni, Ying; Deng, Chao; Ruan, Qinjuan; Ruan, Jun; Zhou, Peng; Duan, Kai","year":2024,"journal":"Endocrine, 86(1), 70-84","doi":"10.1007/s12020-024-03896-z","pmid":"38850440","tags":["tirzepatide","weight-loss","diabetes"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Weight loss was dose-dependent and significant at all three dose levels compared to placebo:\n- 5 mg: -8.07% body weight (about 7.5 kg lost)\n- 10 mg: -10.79% body weight (about 11 kg lost)\n- 15 mg: -11.83% body weight (about 11.5 kg lost)\n\nAll three doses also reduced BMI and waist circumference. The proportion of patients achieving meaningful weight loss thresholds (5%, 10%, 15%, 20%, and 25%) was significantly higher with tirzepatide at all dose levels. Beyond weight, tirzepatide reduced blood pressure, blood sugar, and lipid levels.","whyItMatters":"This meta-analysis includes the SURMOUNT-2 trial data, making it one of the most comprehensive summaries of tirzepatide's weight loss efficacy. The dose-dependent pattern helps clinicians understand the expected range of weight loss at each dose level. The consistent metabolic improvements (blood pressure, lipids, blood sugar) suggest benefits beyond just weight reduction.","specificNumbers":"- 7 RCTs, 4,795 participants\n- 5 mg: -8.07% BW (MD; 95% CI -11.01 to -5.13), -7.5 kg\n- 10 mg: -10.79% BW (MD; 95% CI -13.86 to -7.71), -11.0 kg\n- 15 mg: -11.83% BW (MD; 95% CI -14.52 to -9.14), -11.5 kg\n- All doses reduced BMI, waist circumference, blood pressure, glucose, and lipids\n- GI side effects most common but mild-to-moderate and transient","methodology":"Systematic search of PubMed, Embase, Cochrane, Web of Science, and ClinicalTrials.gov through April 2024. Included 7 randomized controlled trials comparing once-weekly subcutaneous tirzepatide versus placebo in adults with or without type 2 diabetes. Trials ranged from 12 to 72 weeks. Risk of bias assessed using Cochrane RoB-2 tool. Statistical analysis performed with RevMan 5.4.1.","limitations":"Trial durations ranged from 12 to 72 weeks, and pooling across different durations could dilute the long-term effect. The meta-analysis groups trials in patients with and without diabetes, which may differ in weight loss response. Placebo-subtracted differences depend on placebo arm weight changes, which varied across trials. Long-term weight maintenance data beyond 72 weeks is not included."},{"rthcId":"RPEP-09105","title":"Efficacy of Sacubitril Valsartan sodium tablets in patients with heart failure combined with pulmonary infection and long-term recurrence rate.","authors":"Qin, Xiao; Li, Nannan; Zhang, Cuifen; Li, Shanshan; Bu, Fanli","year":2024,"journal":"American journal of translational research, 16(8), 3742-3750","doi":"10.62347/ESYO5136","pmid":"39262724","tags":["natriuretic-peptides","cardiovascular","inflammation"],"studyType":"retrospective cohort","evidenceStrength":"preliminary","keyFinding":"Patients receiving sacubitril/valsartan experienced faster resolution of chest tightness, shortness of breath, cough, and lung crackles compared to the control group. BNP (brain natriuretic peptide, a marker of heart stress) decreased more in the treatment group. Inflammatory markers IL-6, TNF-α, and procalcitonin also improved more with sacubitril/valsartan.\n\nHeart function improved significantly in the treatment group but not the control group. Clinical lung infection scores and organ failure scores were better with treatment. Over 2 years, the readmission rate was lower in the sacubitril/valsartan group, though mortality did not differ.","whyItMatters":"Heart failure patients who develop lung infections face a dangerous combination. The infection worsens heart function, and heart failure impairs the immune response. Sacubitril/valsartan works by blocking neprilysin (which normally breaks down natriuretic peptides), increasing their levels and reducing heart stress. This study suggests the drug may have additional anti-inflammatory benefits in the setting of infection.","specificNumbers":"- 89 patients (48 treatment, 41 control)\n- BNP, IL-6, TNF-α, and PCT all decreased more with sacubitril/valsartan\n- Faster symptom resolution in treatment group\n- Lower hospital readmission rate at 2 years (p < 0.05)\n- No mortality difference between groups (p > 0.05)\n- No significant difference in adverse reactions (p > 0.05)","methodology":"Retrospective study of 89 patients with heart failure and lung infections treated at Dongying People's Hospital in China from January 2019 to May 2020. The control group (41 patients) received conventional treatment. The study group (48 patients) received sacubitril/valsartan in addition to conventional treatment. Outcomes included symptom resolution time, biomarkers (BNP, IL-6, TNF-α, PCT), cardiac function, clinical scores, and 2-year follow-up for readmission and death.","limitations":"This was a small retrospective study at a single hospital with no randomization. The treatment group was slightly larger, suggesting possible selection bias. Without randomization, differences between groups may reflect baseline patient characteristics. The small sample limits the power to detect mortality differences. The 2-year follow-up is based on readmission records, which may not capture all events."},{"rthcId":"RPEP-09106","title":"Enhanced Delivery of Biomolecules into Caco2 Cells Based on the Cell-Penetrating Ability of Keratin Peptides.","authors":"Qin, Xiaojie; Guo, Yujie; Li, Ruilin; Bitter, Johannes H; Scott, Elinor L; Zhang, Chunhui","year":2024,"journal":"ACS applied materials & interfaces, 16(42), 56815-56825","doi":"10.1021/acsami.4c13236","pmid":"39383509","tags":["cell-penetrating","peptide-delivery","bioavailability"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Keratin peptides under 3 kDa (KEP1) showed the highest cell-penetrating ability at a concentration of 2 mg/mL. They delivered fluorescein-labeled insulin (FITC-INS) into Caco2 intestinal cells without covalent bonding, meaning the keratin peptides and insulin were simply mixed together.\n\nThe most effective keratin fragments were 8-19 amino acids long and included hydrophobic peptides (like RVVIEPSPVVV), PPII amphipathic peptides (like PPPVVVTFP), and cysteine-rich peptides (like LCAPTPCGPTPL). Uptake was energy-dependent and primarily used macropinocytosis. The peptides' rich hydrophobic residues and disulfide bonds contributed to their cell-penetrating ability.","whyItMatters":"Oral insulin delivery remains one of the holy grails of drug delivery. If keratin peptides can carry insulin across intestinal cell barriers, it could open a path toward oral insulin or oral delivery of other peptide drugs. Keratin is biocompatible, biodegradable, low-toxicity, and available from natural sources (hair, wool, feathers), making it a practical carrier material.","specificNumbers":"- KEP1 (under 3 kDa): highest cell penetration at 2 mg/mL\n- Most effective fragments: 8-19 amino acids long\n- Uptake mechanism: energy-dependent macropinocytosis\n- Key sequences identified: RVVIEPSPVVV, PPPVVVTFP, LCAPTPCGPTPL\n- No covalent bonding needed between carrier and cargo","methodology":"Researchers fractionated keratin into different molecular weight groups and tested each fraction's ability to enter Caco2 cells (a standard model for intestinal absorption). They used fluorescein-labeled insulin as a cargo molecule. They identified the most effective peptide sequences through further fractionation and analysis. Uptake mechanisms were studied using inhibitors of different cellular uptake pathways.","limitations":"This was tested in Caco2 cells (intestinal cell line in a dish), not in a living organism. Cell culture uptake does not guarantee oral bioavailability in humans because the gut has mucus layers, enzymes, and other barriers not present in cell culture. The insulin was labeled with fluorescein for tracking, which may affect its behavior. No biological activity of the delivered insulin was confirmed."},{"rthcId":"RPEP-09107","title":"Glucagon-like Peptide 1 Receptor Agonists in Cardio-Oncology: Pathophysiology of Cardiometabolic Outcomes in Cancer Patients.","authors":"Quagliariello, Vincenzo; Canale, Maria Laura; Bisceglia, Irma; Iovine, Martina; Giordano, Vienna; Giacobbe, Ilaria; Scherillo, Marino; Gabrielli, Domenico; Maurea, Carlo; Barbato, Matteo; Inno, Alessandro; Berretta, Massimiliano; Tedeschi, Andrea; Oliva, Stefano; Greco, Alessandra; Maurea, Nicola","year":2024,"journal":"International journal of molecular sciences, 25(20)","doi":"10.3390/ijms252011299","pmid":"39457081","tags":["glp-1","cardiovascular","cancer"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Cancer patients face elevated cardiovascular risk from both the cancer itself and cardiotoxic treatments. GLP-1 receptor agonists have shown multiple cardiovascular benefits in large diabetes trials: reduced atherosclerosis, heart failure prevention, and kidney protection.\n\nThe mechanisms involve activation of cAMP and PI3K/AKT pathways (which promote cell survival) and inhibition of NLRP-3 inflammasome and MyD88 (which drive inflammation). These same pathways are involved in chemotherapy-induced cardiac damage, suggesting GLP-1 drugs could offer cardioprotection during cancer treatment.\n\nThe review highlights that no dedicated trial has tested GLP-1 drugs specifically for cardiac protection in cancer patients.","whyItMatters":"Cardio-oncology is a growing field because more cancer patients survive long enough to develop heart disease from their treatments. Many cancer patients also have type 2 diabetes, making them candidates for GLP-1 therapy. If GLP-1 drugs can protect the heart during and after cancer treatment, they could address two problems at once.","specificNumbers":"- GLP-1 drugs activate cAMP and PI3K/AKT pathways\n- GLP-1 drugs inhibit NLRP-3 and MyD88 inflammatory pathways\n- Cardiovascular outcome trials show heart failure and atherosclerosis prevention\n- No dedicated cancer-patient cardiac protection trial exists","methodology":"Narrative review analyzing clinical evidence from cardiovascular outcome trials of GLP-1 drugs and preclinical evidence of their mechanisms in cardiac protection. The authors examined how these mechanisms might apply to cancer-related cardiovascular disease.","limitations":"This is a narrative review with no original data. The cardiovascular outcome trials that showed GLP-1 benefits excluded most cancer patients. The proposed mechanisms are based on preclinical data and extrapolation from diabetes trials. No clinical trial has tested GLP-1 drugs specifically for cardioprotection in cancer patients. The review does not address potential interactions between GLP-1 drugs and cancer treatments."},{"rthcId":"RPEP-09108","title":"Evaluating a Venom-Bioinspired Peptide, NOR-1202, as an Antiepileptic Treatment in Male Mice Models.","authors":"Quintanilha, Maria Varela Torres; Gobbo, Giovanna de Azevedo Mello; Pinheiro, Gabriela Beserra; Souza, Adolfo Carlos Barros de; Camargo, Luana Cristina; Mortari, Marcia Renata","year":2024,"journal":"Toxins, 16(8)","doi":"10.3390/toxins16080342","pmid":"39195752","tags":["venom-peptides","neuroprotection","neuropeptides"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"NOR-1202 showed route-dependent antiepileptic effects. Direct brain injection (intracerebroventricular) protected against pilocarpine-induced generalized seizures and mortality. In the kainic acid model, it improved survival but did not prevent seizures. Systemic administration (subcutaneous or intraperitoneal) showed no antiepileptic activity, suggesting the peptide cannot cross the blood-brain barrier. In a chronic temporal lobe epilepsy model, NOR-1202 did not significantly reduce spontaneous recurrent seizures.","whyItMatters":"Current antiepileptic drugs often fail for temporal lobe epilepsy and cause significant side effects. Venom-derived peptides represent a novel class of potential neurological therapeutics. While NOR-1202's inability to work systemically limits its current utility, understanding its brain-level mechanism could guide development of modified versions that cross the blood-brain barrier.","specificNumbers":"- NOR-1202: analog of occidentalin-1202 (from Polybia occidentalis wasp venom)\n- Acute pilocarpine model: brain injection protected against seizures and mortality\n- Kainic acid model: brain injection improved survival but did not prevent seizures\n- Chronic TLE model: no significant reduction in spontaneous recurrent seizures\n- Systemic (SC or IP) injection: no antiepileptic activity","methodology":"Animal study using male mice in three seizure models: acute pilocarpine-induced, acute kainic acid-induced, and chronic temporal lobe epilepsy (pilocarpine). NOR-1202 was administered via intracerebroventricular injection (using stereotaxic surgery), subcutaneous, or intraperitoneal routes at various doses.","limitations":"Animal study only — no human data. The peptide's inability to work when given systemically is a major limitation for clinical development. Only male mice were used, limiting generalizability. Small sample sizes typical of animal studies. The chronic epilepsy model showed no benefit, raising questions about efficacy in established epilepsy."},{"rthcId":"RPEP-09109","title":"Tirzepatide: unveiling a new dawn in dual-targeted diabetes and obesity management.","authors":"Rabbani, Syed Arman; El-Tanani, Mohamed; Matalka, Ismail I; Rangraze, Imran Rashid; Aljabali, Alaa A A; Khan, Mohammad Ahmed; Tambuwala, Murtaza M","year":2024,"journal":"Expert review of endocrinology & metabolism, 19(6), 487-505","doi":"10.1080/17446651.2024.2395540","pmid":"39194153","tags":["tirzepatide","weight-loss","diabetes","glp-1","cardiovascular"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Tirzepatide's dual mechanism activating both GIP and GLP-1 receptors produces superior efficacy compared to GLP-1-only drugs. The review highlights several key advantages:\n\nGlycemic control: tirzepatide produced larger HbA1c reductions than semaglutide, insulin, and other comparators in the SURPASS trial program. Weight loss: the SURMOUNT trials showed up to 22% body weight reduction in non-diabetic obese patients. Cardiovascular signals: emerging data suggests cardiovascular benefits, potentially setting a new treatment standard.\n\nThe review notes that tirzepatide's GIP component may add benefits beyond what GLP-1 alone provides, including potentially better preservation of bone and muscle mass during weight loss.","whyItMatters":"Tirzepatide represents a new class of dual-agonist therapy. Understanding its full profile, from molecular mechanism to clinical outcomes, helps clinicians and patients make informed treatment decisions. The review consolidates scattered trial data into a single comprehensive reference.","specificNumbers":"- Dual GIP/GLP-1 receptor agonist\n- Superior HbA1c reduction vs semaglutide, insulin, and other comparators\n- Up to 22% body weight reduction in SURMOUNT trials\n- Emerging cardiovascular benefit data\n- Available doses: 5, 10, and 15 mg weekly subcutaneous injection","methodology":"Systematic search of Cochrane, PubMed, Scopus, and Web of Science from inception to April 2024. The review covers tirzepatide's development history, molecular mechanism, pharmacokinetics, pharmacodynamics, clinical efficacy (all SURPASS and SURMOUNT trials), safety profile, and potential cardiovascular effects.","limitations":"Long-term efficacy and safety data beyond 2 years is limited. The cardiovascular outcome trial (SURPASS-CVOT) was not yet complete at the time of review. The review is comprehensive but narrative, without pooled statistical analysis. Head-to-head data against newer competitors (retatrutide, survodutide) is not available. Cost and access barriers are not addressed."},{"rthcId":"RPEP-09110","title":"Human RAMP1 overexpressing mice are resistant to migraine therapies for motion sensitivity.","authors":"Rahman, Shafaqat M; Guo, Linda Jia; Minarovich, Carissa; Moon, Laura; Guo, Anna; Luebke, Anne E","year":2024,"journal":"PloS one, 19(12), e0313482","doi":"10.1371/journal.pone.0313482","pmid":"39652533","tags":["neuropeptides","pain"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"The nestin/hRAMP1 mice showed heightened sensitivity to CGRP's effects at lower doses compared to normal mice. They exhibited increased motion-induced thermoregulation changes (a surrogate for nausea) and greater postural sway (a measure of balance dysfunction). Male nestin/hRAMP1 mice specifically showed increased sway not seen in male controls.\n\nMigraine blocker experiments were challenging to interpret, but the data suggests olcegepant (a CGRP receptor antagonist) could not reverse CGRP-induced or endogenous changes in these mice. Rizatriptan (a triptan) was ineffective in both the engineered mice and controls.\n\nThe authors propose this mouse model represents treatment-resistant migraine with vestibular features.","whyItMatters":"Vestibular migraine (migraine with dizziness and motion sensitivity) affects about 1% of the general population and is poorly understood. Many patients do not respond well to standard migraine treatments. A mouse model that mimics treatment-resistant vestibular migraine could help researchers understand why some patients fail therapy and test new drug candidates.","specificNumbers":"- nestin/hRAMP1 mice: enhanced sensitivity to CGRP at lower doses\n- Increased motion-induced thermoregulation changes (nausea surrogate)\n- Greater postural sway dynamic range\n- Male mice showed increased sway vs male controls\n- Olcegepant: unable to reverse CGRP-related symptoms\n- Rizatriptan: ineffective in both groups","methodology":"Researchers used nestin/hRAMP1 transgenic mice that express elevated human RAMP1 in the nervous system, enhancing CGRP signaling. They measured motion sensitivity using motion-induced thermoregulation (a nausea surrogate) and postural sway using center of pressure assays. They tested olcegepant (CGRP receptor antagonist) and rizatriptan (5-HT1B/1D agonist) as migraine treatments.","limitations":"Mouse behavioral surrogates for nausea and dizziness are imperfect. The authors note the migraine blocker experiments were challenging to interpret. RAMP1 overexpression is a genetic model that may not match the complex neurobiology of human vestibular migraine. Sample sizes for behavioral assays are typically small. Sex differences were observed but not fully explained."},{"rthcId":"RPEP-09111","title":"Migraine inhibitor olcegepant reduces weight loss and IL-6 release in SARS-CoV-2-infected older mice with neurological signs.","authors":"Rahman, Shafaqat M; Buchholz, David W; Imbiakha, Brian; Jager, Mason C; Leach, Justin; Osborn, Raven M; Birmingham, Ann O; Dewhurst, Stephen; Aguilar, Hector C; Luebke, Anne E","year":2024,"journal":"Journal of virology, 98(7), e0006624","doi":"10.1128/jvi.00066-24","pmid":"38814068","tags":["neuropeptides","inflammation","infection"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Older mice (over 18 months, roughly equivalent to elderly humans) infected with mouse-adapted SARS-CoV-2 showed neurological symptoms including fever, dizziness, and nausea in two wild-type strains (C57BL/6J and 129/SvEv).\n\nOlcegepant treatment protected against the permanent weight loss seen after infection. It also dramatically reduced IL-6 levels in both mouse strains. The most striking finding: CGRP-knockout mice (lacking the alpha-CGRP gene entirely) showed virtually no IL-6 release after infection.\n\nThe fever, dizziness, and nausea occurred in all older mice regardless of treatment, suggesting CGRP blockade acts on the inflammatory cascade rather than preventing initial neurological symptoms.","whyItMatters":"COVID-19 neurological symptoms (headache, dizziness, brain fog) have been a persistent challenge. CGRP is a known neuroinflammatory mediator. This study shows that blocking CGRP can reduce the inflammatory cytokine response to SARS-CoV-2, particularly IL-6 (which was associated with severe COVID-19 outcomes). If confirmed, migraine drugs could be repurposed for COVID-19 neurological complications.","specificNumbers":"- Mice over 18 months old (equivalent to elderly humans)\n- Two wild-type strains tested: C57BL/6J and 129/SvEv\n- CGRP-null mice: virtually no IL-6 release\n- Olcegepant: reduced permanent weight loss and IL-6 in both strains\n- All older mice developed fever, dizziness, and nausea regardless of treatment","methodology":"Researchers infected C57BL/6J mice, 129/SvEv mice, and 129S αCGRP-null mice with mouse-adapted SARS-CoV-2. Older mice (over 18 months) were used because age is a major COVID-19 risk factor. They tested olcegepant (CGRP receptor antagonist) for protection against weight loss and measured IL-6 levels and neurological symptoms (fever using thermoregulation, dizziness using postural sway, nausea using behavioral surrogates).","limitations":"This was tested in mice with mouse-adapted SARS-CoV-2, not human COVID-19. The mouse strains and viral adaptation may not replicate human disease. Olcegepant is an intravenous CGRP blocker not approved for clinical use (gepant pills like rimegepant are available). The study measured acute IL-6 and weight loss but not long-term neurological outcomes. The behavioral surrogates for human neurological symptoms are approximations."},{"rthcId":"RPEP-09112","title":"Design, Synthesis, and Evaluation of Oleyl-WRH Peptides for siRNA Delivery.","authors":"Rai, Mrigank Shekhar; Sajid, Muhammad Imran; Moreno, Jonathan; Parang, Keykavous; Tiwari, Rakesh Kumar","year":2024,"journal":"Pharmaceuticals (Basel, Switzerland), 17(8)","doi":"10.3390/ph17081083","pmid":"39204188","tags":["cell-penetrating","peptide-delivery","cancer","peptide-design"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Researchers synthesized oleyl-conjugated peptides of increasing length: oleyl-(WRH)1 through oleyl-(WRH)4. The peptide/siRNA complexes were non-cytotoxic at the working concentration (N/P ratio 40, about 20 μM) against breast cancer (MDA-MB-231, MCF-7), ovarian cancer (SK-OV-3), and normal (HEK-293) cells after 72 hours.\n\nOleyl-(WRH)3 and oleyl-(WRH)4 showed the best siRNA delivery: about 60% and 75% cellular uptake respectively in MDA-MB-231 and SK-OV-3 cells. The complexes formed particles under 200 nm in diameter and remained stable in serum at N/P ratios of 40 or above.\n\nWestern blot confirmed oleyl-(WRH)4 silenced the STAT3 gene by approximately 75% in MDA-MB-231 breast cancer cells and 45% in SK-OV-3 ovarian cancer cells.","whyItMatters":"Gene silencing with siRNA is a powerful approach to cancer treatment, but getting siRNA into cancer cells is the main bottleneck. Most delivery systems use lipid nanoparticles, which have limitations. Peptide-based delivery offers potential advantages in targeting, biocompatibility, and simplicity. This study shows that simple oleyl-peptide conjugates can deliver functional siRNA.","specificNumbers":"- oleyl-(WRH)4: 75% cellular uptake in MDA-MB-231 cells\n- oleyl-(WRH)4: 75% STAT3 gene silencing in MDA-MB-231\n- oleyl-(WRH)4: 45% STAT3 gene silencing in SK-OV-3\n- Non-cytotoxic at N/P 40 (~20 μM)\n- Serum stable at N/P ≥ 40\n- Particle diameter: <200 nm","methodology":"Peptides were synthesized using Fmoc/tBu solid-phase chemistry, purified by HPLC, and characterized. Oleyl groups were conjugated to the peptide N-terminus. Peptide/siRNA complexes were formed at various N/P ratios. Cytotoxicity, serum stability, particle size, cellular uptake (fluorescence), and gene silencing (Western blot for STAT3) were measured in multiple cell lines.","limitations":"This was tested in cell culture only, not in animals or humans. In vitro delivery does not predict in vivo performance, where the siRNA/peptide complex must survive the bloodstream, reach the tumor, and enter cells in a living organism. The study tested only one target gene (STAT3). Serum stability was assessed in vitro, not in circulating blood. The oleyl group may affect biodistribution and clearance in vivo."},{"rthcId":"RPEP-09113","title":"NOVEL AGENTS IN THE MANAGEMENT OF DIABETES AND RISK OF WORSENING DIABETIC RETINOPATHY.","authors":"Rajagopal, Rithwick; McGill, Janet B","year":2024,"journal":"Retina (Philadelphia, Pa.), 44(11), 1851-1859","doi":"10.1097/IAE.0000000000004252","pmid":"39151204","tags":["semaglutide","diabetes","eye-health","side-effects","glp-1"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"In the SUSTAIN-6 cardiovascular outcome trial, semaglutide was associated with approximately 75% increased risk of diabetic retinopathy (DR) worsening. This was a secondary endpoint, not the trial's primary focus. Cases were rare in absolute terms.\n\nInsulin icodec (a novel once-weekly insulin) also showed increased DR worsening compared to daily insulin. No other recent antihyperglycemic agent (SGLT2 inhibitors, DPP-4 inhibitors, other GLP-1 drugs) was associated with DR worsening.\n\nImportantly, after the SUSTAIN-6 finding, nearly all subsequent trials excluded patients with pre-existing diabetic retinopathy. This means the true risk in the most vulnerable population remains unclear. Dedicated semaglutide eye safety studies were underway at the time of publication.\n\nThe most at-risk patients are those with pre-existing high-risk DR, poor baseline blood sugar (where rapid improvement could trigger worsening), and those using insulin.","whyItMatters":"Millions of people take semaglutide for diabetes and weight loss. Understanding eye safety is critical because diabetic retinopathy is the leading cause of blindness in working-age adults. The finding that rapid blood sugar improvement may worsen eye disease is not new (it was known with insulin), but semaglutide's powerful glucose-lowering effect makes this concern more relevant.","specificNumbers":"- SUSTAIN-6: ~75% increased risk of DR worsening with semaglutide\n- Cases were rare in absolute terms\n- Insulin icodec: increased DR worsening vs daily insulin\n- Most vulnerable: pre-existing high-risk DR, poor baseline glucose, insulin users\n- Nearly all subsequent trials excluded patients with pre-existing DR","methodology":"Literature review of clinical trial data for novel antihyperglycemic agents, with focus on diabetic retinopathy as a secondary endpoint or safety outcome. Covers incretin mimetics, SGLT2 inhibitors, long-acting insulins, and insulin delivery systems.","limitations":"DR worsening was a secondary endpoint in SUSTAIN-6, not a primary outcome. The 75% relative risk increase translates to a small absolute risk because DR events were rare. After SUSTAIN-6, trial design changed to exclude DR patients, making it impossible to assess risk in the most vulnerable group. The review does not provide pooled analysis. Long-term eye outcomes on semaglutide are unknown."},{"rthcId":"RPEP-09114","title":"Somatostatin peptides prevent increased human colonic epithelial permeability induced by hypoxia.","authors":"Rajput, Ibrahim; Rajendran, Vazhaikkurichi M; Nickerson, Andrew J; Lodge, J Peter A; Sandle, Geoffrey I","year":2024,"journal":"American journal of physiology. Gastrointestinal and liver physiology, 327(5), G701-G710","doi":"10.1152/ajpgi.00057.2024","pmid":"39226584","tags":["neuropeptides","gut-healing","peptide-safety"],"studyType":"ex vivo","evidenceStrength":"moderate","keyFinding":"Chemical hypoxia (using DNP) increased paracellular permeability in human colon by 52% (p = 0.003). Both somatostatin (2 μM) and octreotide (0.2 μM) prevented this increase whether given before or after the hypoxic insult.\n\nIn rat colon, hypoxia increased total epithelial conductance by 18% (p = 0.016) and macromolecule permeability (FITC-dextran movement) by 43% (p = 0.01). Octreotide pretreatment at 0.2 μM completely prevented both changes.\n\nThe mechanism involves IK channels (intermediate conductance potassium channels, KCa3.1/KCNN4) on the basolateral side of the epithelium. Hypoxia activates these channels, opening the paracellular pathway. Somatostatin and octreotide inhibit IK channels, keeping the gut barrier intact.","whyItMatters":"During abdominal surgery, blood flow to the gut can be compromised, making the gut wall leaky. Bacteria and toxins then cross into the bloodstream, potentially causing sepsis, a leading cause of surgical complications and death. If octreotide can prevent this gut leakiness, it could be given during surgery as a protective measure.","specificNumbers":"- Human colon GS: 52% increase with hypoxia (p = 0.003)\n- SOM (2 μM): prevented GS increase whether given before or after hypoxia\n- OCT (0.2 μM): prevented GS increase whether given before or after hypoxia\n- Rat colon GT: 18% increase with hypoxia (p = 0.016)\n- Rat colon FITC flux: 43% increase with hypoxia (p = 0.01)\n- OCT pretreatment: completely prevented both rat colon changes","methodology":"Researchers used isolated human colon tissue (Ussing chamber technique) and rat distal colon. Chemical hypoxia was induced using 2,4-dinitrophenol (DNP, 100 μM). They measured paracellular shunt conductance (GS) in human tissue and total epithelial conductance (GT) plus macromolecule flux (FITC-dextran 4000) in rat tissue. Somatostatin and octreotide were tested both as pretreatment and rescue treatment.","limitations":"These are ex vivo experiments using isolated tissue, not in vivo animal or human studies. The chemical hypoxia model (DNP) is a simplification of actual surgical ischemia-reperfusion. In a living patient, systemic factors (blood pressure, immune responses, anesthesia drugs) would add complexity. The protective effect has not been tested in an actual surgical setting. The somatostatin and octreotide concentrations used may or may not be achievable in vivo."},{"rthcId":"RPEP-09115","title":"Physiological Appetite Regulation and Bariatric Surgery.","authors":"Ramasamy, Indra","year":2024,"journal":"Journal of clinical medicine, 13(5)","doi":"10.3390/jcm13051347","pmid":"38546831","tags":["glp-1","weight-loss","neuropeptides","hormone-optimization"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Appetite is regulated by two sets of neurons in the hypothalamus. POMC neurons (activated by satiety hormones) suppress appetite. NPY/AgRP neurons (activated by hunger signals) promote eating. Gut hormones modulate this balance.\n\nAfter bariatric surgery, the key changes include: increased GLP-1 (which suppresses appetite and improves blood sugar), increased PYY (peptide YY, which signals fullness), increased oxyntomodulin (which reduces food intake), and decreased ghrelin (the hunger hormone).\n\nThe review highlights that GLP-1 receptor agonists pharmacologically replicate part of this post-surgical response. This explains their effectiveness for weight loss even without surgery. The review also notes that genetic testing can now identify monogenic and polygenic obesity, potentially guiding individualized treatment.","whyItMatters":"Understanding why bariatric surgery works at the hormonal level has directly led to the development of GLP-1 drugs for weight loss. This review connects the dots between surgical outcomes, gut hormone physiology, and drug development. It also introduces the concept of personalized obesity treatment based on genetic profiles.","specificNumbers":"- GLP-1, PYY, oxyntomodulin, CCK: increased after bariatric surgery\n- Ghrelin: decreased after bariatric surgery\n- POMC neurons: activated by anorexigenic hormones\n- NPY/AgRP neurons: activated by orexigenic signals\n- Obesity has both monogenic and polygenic genetic components","methodology":"Narrative review of the physiology of appetite control, including the hypothalamic arcuate nucleus signaling, gut-brain hormone communication, bariatric surgery outcomes, and obesity genetics. Covers both basic science and clinical evidence.","limitations":"This is a narrative review without systematic methodology or pooled analysis. It covers a broad scope (physiology, surgery, genetics, pharmacology) at a high level without deep analysis of any single topic. The genetic section is brief and does not detail specific gene-treatment matching. The review does not address long-term safety of GLP-1 drugs or compare them quantitatively to surgery."},{"rthcId":"RPEP-09116","title":"A bird's-eye view of the biological mechanism and machine learning prediction approaches for cell-penetrating peptides.","authors":"Ramasundaram, Maduravani; Sohn, Honglae; Madhavan, Thirumurthy","year":2024,"journal":"Frontiers in artificial intelligence, 7, 1497307","doi":"10.3389/frai.2024.1497307","pmid":"39839972","tags":["cell-penetrating","peptide-design","peptide-delivery"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"The review compared multiple CPP prediction tools using standard performance metrics (accuracy, sensitivity, specificity, Matthews correlation coefficient) on independent test datasets.\n\nCommonly used algorithms include support vector machines (SVM), random forests (RF), gradient-boosted decision trees (GBDT), and various types of artificial neural networks (ANN). The review found that tool performance varies significantly depending on dataset size, feature encoding method, and the specific evaluation metrics used.\n\nKey factors that affect prediction accuracy include: the size and quality of the training dataset, how peptide sequences are encoded as numerical features, and whether the tool uses sequence-based, structure-based, or hybrid features. The review emphasizes the importance of evaluating tools on independent test sets rather than cross-validation alone.","whyItMatters":"Drug delivery is one of the biggest bottlenecks in medicine. Cell-penetrating peptides could solve this for many drugs that cannot get into cells. But designing effective CPPs requires testing thousands of candidates. Machine learning can pre-screen sequences computationally, saving years of lab work. This review guides researchers toward the best available tools.","specificNumbers":"- Common algorithms: SVM, RF, GBDT, ANN\n- Performance metrics: accuracy, sensitivity, specificity, MCC\n- Datasets: produced by high-throughput sequencing and computational methods\n- Tools evaluated on independent test sets for fair comparison","methodology":"Comprehensive literature review of machine learning-based CPP prediction tools. The authors compared algorithms, dataset sizes, feature encoding methods, software accessibility, evaluation metrics, and prediction scores across published tools. Performance was evaluated using accuracy, sensitivity, specificity, and MCC on independent datasets.","limitations":"The review is comprehensive but does not perform a new benchmarking analysis. Tool comparisons across different publications may not be fair because they use different datasets and evaluation protocols. Some older tools may no longer be maintained or accessible. The review focuses on classification (CPP or not) and does not deeply cover regression models that predict uptake quantities."},{"rthcId":"RPEP-09117","title":"Effectiveness and safety of a GLP-1 agonist in obese patients with inflammatory bowel disease.","authors":"Ramos Belinchón, Clara; Martínez-Lozano, Helena; Serrano Moreno, Clara; Hernández Castillo, Diego; Lois Chicharro, Pablo; Ferreira Ocampo, Pablo; Marín-Jiménez, Ignacio; Bretón Lesmes, Irene; Menchén, Luis","year":2024,"journal":"Revista espanola de enfermedades digestivas, 116(9), 478-483","doi":"10.17235/reed.2024.10305/2024","pmid":"38767015","tags":["semaglutide","liraglutide","glp-1","gut-healing","weight-loss"],"studyType":"case series","evidenceStrength":"preliminary","keyFinding":"Sixteen obese patients with IBD (9 Crohn's disease, 7 ulcerative colitis) received semaglutide 1.0 mg or liraglutide 3.0 mg for obesity. Their median starting BMI was 35.\n\nAt 6 months, median weight change was -6.2%. 58.3% (7 of 12 evaluable patients) achieved at least 5% weight loss. IBD activity scores showed no significant changes during follow-up, meaning the drugs did not trigger disease flares.\n\nSide effects were mild. Nausea was the most common at 13.3%. One patient discontinued due to diarrhea. No serious adverse events were reported.","whyItMatters":"Obesity is common in IBD patients and worsens their disease outcomes. But GLP-1 drugs have not been studied in IBD patients, raising concerns that GI side effects could worsen IBD symptoms or trigger flares. This small study provides the first evidence that GLP-1 drugs are safe and effective for weight loss in this population.","specificNumbers":"- 16 patients (9 Crohn's, 7 ulcerative colitis)\n- Median baseline BMI: 35\n- Median weight change at 6 months: -6.2%\n- 5% weight loss achieved: 58.3% (7/12)\n- Nausea: 13.3%\n- 1 withdrawal due to diarrhea\n- IBD activity: no significant changes","methodology":"Retrospective case series of consecutive IBD patients who received GLP-1 drugs (semaglutide 1.0 mg or liraglutide 3.0 mg) for obesity between 2019 and 2021. The coprimary endpoints were percentage weight change at 6 months and proportion achieving 5% or more weight loss. IBD activity and safety were monitored.","limitations":"This is a very small retrospective case series with only 16 patients and no control group. The follow-up was only 6 months. IBD activity was assessed using clinical scores, not endoscopy or biomarkers, which could miss subclinical inflammation. The study cannot distinguish between semaglutide and liraglutide effects. Publication bias may favor reporting positive results."},{"rthcId":"RPEP-09118","title":"Neurokinin B Administration Induces Dose Dependent Proliferation of Seminal Vesicles in Adult Rats.","authors":"Ramzan, Muhammad Haris; Shah, Mohsin; Ramzan, Faiqah","year":2024,"journal":"Current protein & peptide science, 25(4), 339-352","doi":"10.2174/0113892037264538231128072614","pmid":"38243941","tags":["neuropeptides","fertility"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Neurokinin B at three doses (1 μg, 1 ng, and 10 pg) administered intraperitoneally for 12 days increased seminal vesicle weight, epithelial height, and seminal fructose levels in a dose-dependent manner. Senktide (an NK3R agonist) produced similar effects. SB222200 (an NK3R antagonist) slightly decreased these parameters.\n\nLight microscopy showed increased epithelial height and folding in all neurokinin B and senktide groups. Immunohistochemistry for NK3 receptor expression showed no change with treatment, suggesting the receptor is constitutively expressed.\n\nCritically, all effects reversed when rats were kept for 12 days without treatment, indicating the changes are stimulatory and reversible rather than permanent.","whyItMatters":"Neurokinin B is known to stimulate reproductive hormones through GnRH (gonadotropin-releasing hormone). But its direct effects on reproductive organs like seminal vesicles were unknown. This study shows neurokinin B has a stimulatory effect on seminal vesicle growth and function, which could be relevant for understanding male fertility and potentially for fertility treatments.","specificNumbers":"- 10 rats per group (6 groups)\n- Treatment: 12 days intraperitoneal\n- Reversal period: 12 days without treatment\n- Neurokinin B doses: 1 μg, 1 ng, 10 pg\n- Senktide (agonist): 1 μg\n- SB222200 (antagonist): 1 μg\n- Increased: seminal vesicle weight, epithelial height, seminal fructose\n- NK3R expression: unchanged\n- All effects reversed after treatment cessation","methodology":"Adult male Sprague Dawley rats (n=10 per group) received 12 days of intraperitoneal injections: neurokinin B at 1 μg, 1 ng, or 10 pg; senktide (NK3R agonist) at 1 μg; or SB222200 (NK3R antagonist) at 1 μg. Half were sacrificed after treatment, half kept for 12 more days without treatment (reversal period). Seminal vesicles were analyzed by light microscopy, immunohistochemistry, and seminal fructose measurement.","limitations":"This was tested in rats, not people. The intraperitoneal injection route delivers peptide systemically, which differs from natural neurokinin B release patterns. The dose range spans a million-fold (1 μg to 10 pg), making dose-response interpretation complex. The study measured structural and biochemical changes but not actual fertility or sperm quality. NK3R expression did not change, which limits mechanistic interpretation."},{"rthcId":"RPEP-09119","title":"SPIRIT: Assessing Clinical Parameters Associated with Using IDegLira in Patients with Type 2 Diabetes in a Real-World Setting in Colombia.","authors":"Ramírez-Rincón, Alex; Henao-Carrillo, Diana; Omeara, Miguel; Oliveros, Julio; Assaf, José; Ordóñez, Jaime E; Prasad, Preethy; Alzate, María Alejandra","year":2024,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 15(7), 1535-1545","doi":"10.1007/s13300-024-01593-8","pmid":"38717577","tags":["liraglutide","diabetes","glp-1"],"studyType":"retrospective cohort","evidenceStrength":"moderate","keyFinding":"After approximately 26 weeks on IDegLira:\n- HbA1c decreased by 1.3% (from 9.1% to 7.8%, p < 0.0001)\n- Body weight decreased by 1 kg (from 76.1 to 75.1 kg, p < 0.0001)\n- No severe hypoglycemic events observed\n- Mean final IDegLira dose: 21.3 units\n\nThese results were achieved in patients who had previously been on basal insulin (with or without oral diabetes drugs) and were not reaching their blood sugar targets. The combination provided better control with modest weight loss rather than the weight gain typically seen with intensified insulin therapy.","whyItMatters":"In Latin America, many diabetes patients on basal insulin do not reach their blood sugar targets. Adding a GLP-1 drug through a fixed-ratio combination simplifies treatment (one injection instead of two) and adds weight loss benefit. Real-world data from the region confirms that IDegLira works outside clinical trial conditions in this population.","specificNumbers":"- 175 patients across 10 centers in Colombia\n- Baseline HbA1c: 9.1%\n- Final HbA1c: 7.8% (reduction: 1.3%, p < 0.0001)\n- Baseline weight: 76.1 kg\n- Final weight: 75.1 kg (reduction: 1.0 kg, p < 0.0001)\n- Mean final dose: 21.3 units/day\n- Severe hypoglycemia: 0 events","methodology":"SPIRIT was a non-interventional, single-arm, retrospective chart review conducted at 10 clinical centers across Colombia. Data were collected from medical records of 175 patients with type 2 diabetes who had been switched from basal insulin (± oral antidiabetics) to IDegLira at least 26 ± 6 weeks before data collection. Registered on ClinicalTrials.gov (NCT05324462).","limitations":"Retrospective, single-arm design with no control group. Without a comparator, the improvement could partly reflect attention effects or concomitant lifestyle changes. The 26-week follow-up is relatively short. Only 175 patients were included. Colombia-specific healthcare factors may limit generalizability. The study relied on medical records, which may have incomplete data."},{"rthcId":"RPEP-09120","title":"Evaluating the effectiveness and safety of various Tirzepatide dosages in the management of Type 2 diabetes mellitus: a network meta-analysis of randomized controlled trials.","authors":"Rangwala, Hussain Sohail; Fatima, Hareer; Ali, Mirha; Mustafa, Muhammad Saqlain; Shafique, Muhammad Ashir; Rangwala, Burhanuddin Sohail; Abbas, Syed Raza","year":2024,"journal":"Journal of diabetes and metabolic disorders, 23(1), 1199-1222","doi":"10.1007/s40200-024-01412-8","pmid":"38932909","tags":["tirzepatide","diabetes","weight-loss","dosing","side-effects"],"studyType":"network meta-analysis","evidenceStrength":"strong","keyFinding":"Compared to tirzepatide 5 mg:\n- 10 mg: additional 19% HbA1c reduction (MD: -0.19), additional 1.96 kg weight loss\n- 15 mg: additional 31% HbA1c reduction (MD: -0.32), additional 3.31 kg weight loss, and improved fasting glucose (MD: -6.71 mg/dL)\n\nThe dose-response relationship was clear and consistent across the 10 studies. Higher doses produced incrementally better metabolic outcomes.\n\nFor safety, gastrointestinal events were numerically higher with increasing doses but without reaching statistical significance. There were no significant differences across doses for death, nausea, diarrhea, vomiting, dyspepsia, decreased appetite, injection site reactions, hypoglycemia, treatment discontinuation, or serious adverse events.","whyItMatters":"Most patients start tirzepatide at 5 mg and titrate up. Knowing exactly how much additional benefit each dose step provides helps clinicians and patients make informed titration decisions. This analysis quantifies the dose-response relationship and shows that higher doses are both more effective and reasonably safe.","specificNumbers":"- 10 randomized controlled trials\n- TZP 10 mg vs 5 mg: HbA1c MD -0.19, weight MD -1.96 kg\n- TZP 15 mg vs 5 mg: HbA1c MD -0.32, weight MD -3.31 kg\n- TZP 15 mg vs 5 mg: fasting glucose MD -6.71 mg/dL\n- No significant differences in serious adverse events across doses\n- GI side effects: numerically higher at higher doses but not statistically significant","methodology":"Network meta-analysis of 10 randomized controlled trials comparing different tirzepatide doses for type 2 diabetes, searched through November 2023. Outcomes included HbA1c change, weight change, fasting glucose, and adverse events. Quality assessed using Cochrane risk-of-bias tool. Network meta-analysis allowed indirect comparisons between dose levels.","limitations":"Network meta-analysis makes indirect comparisons across different trial populations, which introduces heterogeneity. The included studies had varying durations, comparator groups, and patient populations. The GI side effect analysis may be underpowered because these events are common and variable. The analysis does not compare tirzepatide to other drugs (only compares its own doses). Cost-effectiveness is not addressed."},{"rthcId":"RPEP-09121","title":"TANGO1 inhibitors reduce collagen secretion and limit tissue scarring.","authors":"Raote, Ishier; Rosendahl, Ann-Helen; Häkkinen, Hanna-Maria; Vibe, Carina; Küçükaylak, Ismail; Sawant, Mugdha; Keufgens, Lena; Frommelt, Pia; Halwas, Kai; Broadbent, Katrina; Cunquero, Marina; Castro, Gustavo; Villemeur, Marie; Nüchel, Julian; Bornikoel, Anna; Dam, Binita; Zirmire, Ravindra K; Kiran, Ravi; Carolis, Carlo; Andilla, Jordi; Loza-Alvarez, Pablo; Ruprecht, Verena; Jamora, Colin; Campelo, Felix; Krüger, Marcus; Hammerschmidt, Matthias; Eckes, Beate; Neundorf, Ines; Krieg, Thomas; Malhotra, Vivek","year":2024,"journal":"Nature communications, 15(1), 3302","doi":"10.1038/s41467-024-47004-1","pmid":"38658535","tags":["collagen-peptides","cell-penetrating","wound-healing","skin-repair"],"studyType":"in vitro/animal","evidenceStrength":"preliminary","keyFinding":"The peptide inhibitors specifically target the primary binding interface between TANGO1 and cTAGE5, two proteins required for collagen export from the endoplasmic reticulum. Treatment reduced protein levels of both TANGO1 and cTAGE5, blocking the secretion of multiple extracellular matrix components including collagens, fibrillin, and fibronectin.\n\nIn zebrafish, the peptide inhibitors altered tissue architecture and reduced granulation tissue formation during wound healing. In human dermal fibroblasts and cells from scleroderma patients (who have generalized fibrosis), the inhibitors reduced secretion of ECM proteins.","whyItMatters":"Fibrotic diseases (lung fibrosis, liver cirrhosis, scleroderma, keloid scars) affect millions and have few effective treatments. Rather than targeting individual collagen types, this approach blocks the export machinery that all large ECM proteins share. This could be a broad-spectrum anti-fibrotic strategy.","specificNumbers":"- Reduced TANGO1 and cTAGE5 protein levels\n- Inhibited secretion of collagens, fibrillin, and fibronectin\n- Reduced granulation tissue in zebrafish wound healing\n- Effective in human dermal fibroblasts and scleroderma patient cells","methodology":"Researchers designed membrane-permeant peptide inhibitors targeting the TANGO1-cTAGE5 binding interface. They tested the peptides in cell culture (human dermal fibroblasts and scleroderma patient cells), measuring secretion of ECM proteins. In vivo testing used zebrafish cutaneous wound healing models to assess granulation tissue formation.","limitations":"The in vivo data is from zebrafish, not mammals. Zebrafish wound healing differs from human scarring. The peptide inhibitors block secretion of multiple ECM proteins, not just collagen, which could cause off-target effects on normal tissue maintenance. Long-term safety of reducing ECM secretion is unknown. The peptides are membrane-permeant, but delivery to deep tissues in mammals would need optimization."},{"rthcId":"RPEP-09122","title":"Oxytocin as a treatment for alcohol use disorder and heavy drinking: A narrative review.","authors":"Rastogi, Kriti; Weerts, Elise M; Ellis, Jennifer D","year":2024,"journal":"Experimental and clinical psychopharmacology, 32(6), 625-638","doi":"10.1037/pha0000741","pmid":"39298263","tags":["oxytocin","addiction"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Oxytocin shows dose-dependent effects on alcohol use behavior: low doses do not significantly affect drinking or tolerance, but higher doses given before alcohol exposure produce varying behavioral and physiological results. In preclinical (animal) studies, oxytocin reduced withdrawal symptoms and alcohol self-administration. In clinical (human) studies, oxytocin may decrease neural cue reactivity (how strongly the brain responds to alcohol-related cues) and withdrawal symptoms.\n\nThe timing and dose of oxytocin appear critical — the peptide seems to work by strengthening stress-coping mechanisms and reducing anxiety, which are key drivers of alcohol craving and relapse. However, results are inconsistent across studies, and the optimal dosing and treatment protocols remain unclear.","whyItMatters":"Alcohol use disorder affects an estimated 29.5 million Americans, yet only three medications are FDA-approved for its treatment — and all have limited effectiveness. Oxytocin represents a fundamentally different therapeutic approach: rather than directly blocking alcohol's effects, it targets the social bonding and stress-response systems that underlie addiction vulnerability. If effective, it could address the emotional and social drivers of alcohol dependence that current medications largely ignore.","specificNumbers":"","methodology":"Narrative review of preclinical (animal) and clinical (human) studies on intranasal and systemic oxytocin for alcohol use disorders and heavy drinking. The review also discusses trial design frameworks and the parameters (dosing, timing, route of administration) that vary across studies and influence outcomes.","limitations":"This is a narrative review, not a systematic review or meta-analysis, so it does not quantitatively pool results. The existing evidence base is small, with inconsistent findings across studies. Dosing protocols, routes of administration, and outcome measures vary widely. Most human studies are small and short-term. The mechanisms by which oxytocin affects alcohol behavior are not fully understood."},{"rthcId":"RPEP-09123","title":"Conjugation of CRAMP18-35 Peptide to Chitosan and Hydroxypropyl Chitosan via Copper-Catalyzed Azide-Alkyne Cycloaddition and Investigation of Antibacterial Activity.","authors":"Rathinam, Sankar; Sørensen, Kasper K; Hjálmarsdóttir, Martha Á; Thygesen, Mikkel B; Másson, Már","year":2024,"journal":"International journal of molecular sciences, 25(17)","doi":"10.3390/ijms25179440","pmid":"39273387","tags":["antimicrobial-peptides","peptide-design","infection"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"CRAMP18-35 (a fragment of mouse cathelicidin) was conjugated to chitosan and hydroxypropyl chitosan using copper-catalyzed azide-alkyne cycloaddition (CuAAC, a click chemistry reaction). The degree of substitution was 0.20 for chitosan and 0.13 for HPC conjugates.\n\nThe conjugates showed selective antibacterial activity against Gram-negative bacteria (E. coli and P. aeruginosa) and lacked activity against Gram-positive bacteria (S. aureus and E. faecalis). This selectivity was a notable finding because the free peptide is typically active against both types.","whyItMatters":"Antibiotic resistance is a global crisis. Gram-negative bacteria are especially hard to treat because of their double membrane. Combining antimicrobial peptides with chitosan could create wound dressings or coatings that kill resistant bacteria. Chitosan itself is biocompatible and biodegradable.","specificNumbers":"- Peptide: CRAMP18-35 (mouse cathelicidin fragment)\n- Degree of substitution: 0.20 (chitosan), 0.13 (HPC)\n- Active against: E. coli, P. aeruginosa (Gram-negative)\n- Inactive against: S. aureus, E. faecalis (Gram-positive)\n- Conjugation method: CuAAC click chemistry","methodology":"Chitosan azide and HPC-azide were prepared by reacting with imidazole sulfonyl azide hydrochloride. CRAMP18-35 with an N-terminal pentynoyl group was conjugated via CuAAC. Conjugates were characterized by IR spectroscopy and proton NMR. Antibacterial activity was tested against two Gram-positive and two Gram-negative bacterial species.","limitations":"The selectivity change (losing Gram-positive activity after conjugation) was not explained mechanistically. The conjugation may alter the peptide's ability to interact with Gram-positive cell walls. In vitro antibacterial testing does not predict in vivo wound healing efficacy. Copper catalyst residues from click chemistry could be a biocompatibility concern. No cytotoxicity testing was reported."},{"rthcId":"RPEP-09124","title":"ToxinPred 3.0: An improved method for predicting the toxicity of peptides.","authors":"Rathore, Anand Singh; Choudhury, Shubham; Arora, Akanksha; Tijare, Purva; Raghava, Gajendra P S","year":2024,"journal":"Computers in biology and medicine, 179, 108926","doi":"10.1016/j.compbiomed.2024.108926","pmid":"39038391","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09125","title":"Insights on discovery, efficacy, safety and clinical applications of ghrelin receptor agonist capromorelin in veterinary medicine.","authors":"Rathore, Manisha; Das, Nabanita; Ghosh, Nayan; Guha, Rajdeep","year":2024,"journal":"Veterinary research communications, 48(1), 1-10","doi":"10.1007/s11259-023-10184-0","pmid":"37493940","tags":["ghrp","hormone-optimization"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Capromorelin acts on the growth hormone secretagogue receptor 1a (GHSR-1a), the same receptor activated by the natural hunger hormone ghrelin. When natural ghrelin production is disrupted, capromorelin substitutes to stimulate growth hormone release and appetite.\n\nIn dogs, capromorelin (Entyce) increases food intake and is FDA-approved for appetite stimulation. In cats, capromorelin (Elura) is approved for managing weight loss associated with chronic kidney disease. The drug also stimulates growth hormone and IGF-1, which may help prevent muscle wasting and cachexia.","whyItMatters":"Ghrelin receptor agonists have been studied for decades in humans for appetite stimulation, growth hormone deficiency, and cachexia. Capromorelin's success in veterinary medicine provides proof-of-concept for this drug class. Understanding its effects in dogs and cats may inform future human applications of ghrelin receptor agonists.","specificNumbers":"- FDA-approved for dogs: May 2016 (Entyce, Aratana Therapeutics)\n- FDA-approved for cats: 2020 (Elura, Elanco)\n- Target: GHSR-1a (growth hormone secretagogue receptor 1a)\n- Effects: appetite stimulation, growth hormone release, IGF-1 increase","methodology":"Narrative review of published literature covering the discovery, development, efficacy, safety, and clinical applications of capromorelin in veterinary medicine.","limitations":"This is a veterinary medicine review. Results in dogs and cats may not directly translate to humans. The review does not include new original data. Capromorelin's long-term effects in animals are still being studied. The drug is not approved for human use."},{"rthcId":"RPEP-09126","title":"Medication \"underuse\" headache.","authors":"Rattanawong, Wanakorn; Rapoport, Alan; Srikiatkhachorn, Anan","year":2024,"journal":"Cephalalgia : an international journal of headache, 44(4), 3331024241245658","doi":"10.1177/03331024241245658","pmid":"38613233","tags":["neuropeptides","pain"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"The review identifies four forms of medication underuse in migraine:\n1. Taking inappropriate medications for the pain level and disability\n2. Taking medication too late (more than 60 minutes after onset, or after allodynia develops)\n3. Discontinuing treatment due to side effects or perceived lack of effect\n4. Poor adherence to preventive medications\n\nFor acute treatment, the key problem is failing to halt the progression from peripheral nerve activation to central sensitization. Once central sensitization occurs (marked by allodynia, where normal touch becomes painful), acute medications are much less effective.\n\nFor preventive treatment, inadequate efficacy and side effects of conventional drugs lead to high discontinuation rates. Anti-CGRP medications partially address this by offering better tolerability and targeting the underlying CGRP pathway. The review suggests starting anti-CGRP treatment during low-frequency episodic migraine rather than waiting until attacks become frequent or chronic.","whyItMatters":"The migraine field has focused heavily on medication overuse headache. This review highlights the opposite problem: not treating enough. If undertreated episodic migraine progresses to chronic migraine, patients face far worse outcomes and quality of life. The recommendation to start CGRP-targeting preventives earlier challenges current stepwise treatment guidelines.","specificNumbers":"- Acute medication should be taken within 60 minutes of migraine onset\n- Central sensitization (allodynia) marks the point where acute treatment effectiveness drops\n- Anti-CGRP treatment may be more beneficial when started during low-frequency episodic migraine\n- Conventional preventive drugs have high discontinuation rates due to side effects","methodology":"Comprehensive narrative review of published evidence on medication underuse in migraine, covering both acute and preventive treatments. Examines the pathophysiology of migraine progression from peripheral to central sensitization.","limitations":"This is a narrative review advocating a position. The evidence for early CGRP treatment preventing chronification is still limited. The concept of medication underuse is not well-defined in clinical guidelines. Some of the pathophysiology described is based on animal models. The review does not address cost-effectiveness of early CGRP treatment or practical barriers to access."},{"rthcId":"RPEP-09127","title":"Sweetening the deal: an infodemiological study of worldwide interest in semaglutide using Google Trends extended for health application programming interface.","authors":"Raubenheimer, Jacques Eugene; Myburgh, Pieter Hermanus; Bhagavathula, Akshaya Srikanth","year":2024,"journal":"BMC global and public health, 2(1), 63","doi":"10.1186/s44263-024-00095-w","pmid":"39681910","tags":["semaglutide","weight-loss","regulatory"],"studyType":"infodemiological","evidenceStrength":"moderate","keyFinding":"Semaglutide search interest increased dramatically from 2022 onward across most of the 27 countries studied. The US and Canada had the largest and most sustained interest.\n\nNatural language processing of search queries revealed that weight loss was the dominant theme in most countries. A diabetes theme was generally absent or weak, confirming that public interest is driven by weight loss rather than the drug's original purpose.\n\nMedia coverage partially explained search interest (Granger causality analysis), with the UK and Germany showing strong relationships between news reports and subsequent search spikes. A single Dr. Oz TV episode coincided with search peaks across multiple countries. Some countries showed concerning themes: Australia, Chile, South Africa, and the UK had searches for buying Ozempic from specific retailers, and Germany had searches for obtaining it without a prescription.","whyItMatters":"The global surge in semaglutide interest for weight loss, driven by social media and mainstream media, created supply shortages that affected diabetes patients. Understanding the drivers of this interest can help regulators and healthcare systems prepare for similar surges with future drugs. The finding that weight loss dominates over diabetes searches confirms the off-label demand is consumer-driven.","specificNumbers":"- 27 countries included\n- Search interest surged from 2022 onward\n- US and Canada: largest sustained interest\n- Weight loss: dominant theme in most countries\n- Diabetes theme: absent or weak in most countries\n- Up to 4 significant within-country changepoints identified\n- Dr. Oz TV episode: coincided with multi-country search peaks","methodology":"Researchers used Google Trends Extended for Health (GTEH) with multiple sampling to retrieve regional online interest from all countries. They included 27 countries with sufficient search volume. Granger causality analysis tested whether media coverage predicted search interest. Joinpoint regression identified trend changepoints. Natural language processing identified themes in top search queries.","limitations":"Google search data is a proxy for interest, not actual drug use or prescribing patterns. Countries with low internet penetration are underrepresented. The GTEH tool provides relative interest, not absolute search volumes. The study period ended in August 2023 and may not capture more recent trends. Social media data was not directly analyzed."},{"rthcId":"RPEP-09128","title":"Effect of GLP-1 Receptor Agonist on Ischemia Reperfusion Injury in Rats with Metabolic Syndrome.","authors":"Ravic, Marko; Srejovic, Ivan; Novakovic, Jovana; Andjic, Marijana; Sretenovic, Jasmina; Muric, Maja; Nikolic, Marina; Bolevich, Sergey; Alekseevich Kasabov, Kirill; Petrovich Fisenko, Vladimir; Stojanovic, Aleksandra; Jakovljevic, Vladimir","year":2024,"journal":"Pharmaceuticals (Basel, Switzerland), 17(4)","doi":"10.3390/ph17040525","pmid":"38675485","tags":["exenatide","dulaglutide","glp-1","cardiovascular"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"After 6 weeks of treatment in rats with metabolic syndrome:\n- Exenatide improved ejection fraction by 3% vs untreated MetS group\n- Dulaglutide improved ejection fraction by 7% vs untreated MetS group\n- Histology showed reduced cardiomyocyte cross-sectional area: 11% reduction with exenatide, 18% with dulaglutide\n- Both drugs reduced oxidative stress biomarkers\n- Dulaglutide showed a slight advantage overall","whyItMatters":"People with metabolic syndrome have higher risk of heart attacks and worse outcomes when they occur. GLP-1 drugs are prescribed for diabetes and weight loss in this population. Evidence that they also protect the heart during a heart attack would be a major additional benefit. This animal study provides mechanistic support for the cardiovascular benefits seen in human clinical trials.","specificNumbers":"- 24 rats in 3 groups (8 per group)\n- Exenatide dose: 5 μg/kg\n- Dulaglutide dose: 0.6 mg/kg\n- Treatment duration: 6 weeks\n- Ejection fraction improvement: 3% (exenatide), 7% (dulaglutide)\n- Cardiomyocyte area reduction: 11% (exenatide), 18% (dulaglutide)","methodology":"24 Wistar albino rats were given metabolic syndrome through diet. They were divided into three groups: untreated MetS, exenatide-treated (5 μg/kg), and dulaglutide-treated (0.6 mg/kg). After 6 weeks, heart function was assessed by echocardiography in living animals. Hearts were then removed and subjected to simulated ischemia-reperfusion injury using a Langendorff apparatus. Tissue was analyzed histologically and for oxidative stress biomarkers.","limitations":"Tested in rats with diet-induced metabolic syndrome, not humans. The simulated heart attack (Langendorff) is a simplified model. The MetS model may not replicate all features of human metabolic syndrome. Only 8 rats per group limits statistical power. The treatment was given before the heart attack (pretreatment), not after. The 6-week duration may not capture long-term effects."},{"rthcId":"RPEP-09129","title":"Effect of GLP-1 receptor agonists on weight and cardiovascular outcomes: A review.","authors":"Raza, Fatima Ali; Altaf, Rafiya; Bashir, Talha; Asghar, Fatima; Altaf, Rabiya; Tousif, Sohaib; Goyal, Aman; Mohammed, Aisha; Mohammad, Mahnoor Faisal; Anan, Mahfuza; Ali, Sajjad","year":2024,"journal":"Medicine, 103(44), e40364","doi":"10.1097/MD.0000000000040364","pmid":"39496023","tags":["semaglutide","liraglutide","glp-1","weight-loss","cardiovascular"],"studyType":"review","evidenceStrength":"strong","keyFinding":"GLP-1 receptor agonists work by mimicking the natural gut hormone GLP-1, which reduces appetite and slows stomach emptying. Semaglutide and liraglutide are the two GLP-1 drugs FDA-approved for weight management.\n\nBeyond weight loss, these drugs show early evidence of cardiovascular benefits in obese patients, including reduced cardiovascular events and improved risk factors. The SELECT trial showed semaglutide reduced major cardiovascular events by 20% in obese people without diabetes.\n\nCommon side effects are gastrointestinal (nausea, vomiting, diarrhea) and are usually mild to moderate. The review discusses strategies for managing these effects, including gradual dose escalation.","whyItMatters":"Diet and exercise alone produce modest long-term weight loss. GLP-1 drugs have changed the treatment landscape by producing 15-20% weight loss in clinical trials. The additional cardiovascular benefits make them potentially life-saving, not just cosmetic, treatments for obesity.","specificNumbers":"- Semaglutide and liraglutide: both FDA-approved for weight loss\n- GLP-1 drugs: significant and sustained weight loss in trials\n- SELECT trial: 20% reduction in major cardiovascular events with semaglutide in obesity\n- Common side effects: nausea, vomiting, diarrhea (usually mild-moderate)","methodology":"Narrative review of published literature covering GLP-1 receptor agonist mechanisms, clinical trial results for weight loss, cardiovascular outcome data, adverse effects, and side effect management strategies.","limitations":"This is a narrative review without systematic methodology or meta-analysis. It does not cover tirzepatide or newer multi-agonists. The cardiovascular outcome data for obesity (as opposed to diabetes) is limited to the SELECT trial for semaglutide. Long-term effects beyond 2-3 years are unknown. Weight regain after stopping the drugs is not thoroughly addressed."},{"rthcId":"RPEP-09130","title":"Stearic acid-based nanoparticles loaded with antibacterial peptides - Bacitracin and LL-37: Selection of manufacturing parameters, cytocompatibility, and antibacterial efficacy.","authors":"Reczyńska-Kolman, Katarzyna; Ochońska, Dorota; Brzychczy-Włoch, Monika; Pamuła, Elżbieta","year":2024,"journal":"International journal of pharmaceutics, 667(Pt A), 124876","doi":"10.1016/j.ijpharm.2024.124876","pmid":"39477135","tags":["ll-37","antimicrobial-peptides","peptide-delivery","infection"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"The researchers found that the type of organic solvent used during manufacturing had a major effect on nanoparticle shape. Chloroform produced the best spherical nanoparticles. Size and polydispersity were affected by surfactant concentration, stearic acid concentration, and homogenization amplitude.\n\nOnce optimized, the nanoparticles were successfully loaded with LL-37. The LL-37-loaded nanoparticles maintained their morphology and cytocompatibility (did not harm cells). They showed antibacterial activity against the reference strain of Streptococcus pyogenes (ATCC 12384).","whyItMatters":"LL-37 is the body's own antimicrobial peptide but breaks down quickly when used as a drug. Encapsulating it in lipid nanoparticles could protect it from degradation and deliver it to infection sites. Streptococcus pyogenes causes conditions ranging from strep throat to necrotizing fasciitis, and antibiotic-resistant strains are emerging.","specificNumbers":"- Optimal solvent: chloroform for spherical morphology\n- LL-37 loading did not alter morphology or cytocompatibility\n- Active against Streptococcus pyogenes ATCC 12384\n- Key parameters: surfactant concentration, stearic acid concentration, homogenization amplitude","methodology":"Emulsification/solvent diffusion method was used to fabricate stearic acid nanoparticles. Manufacturing parameters (solvent type, surfactant concentration, stearic acid concentration, homogenization amplitude) were systematically optimized. LL-37 was loaded into optimized nanoparticles. Properties measured included morphology, size, polydispersity, cytotoxicity, and antibacterial activity.","limitations":"Antibacterial activity was tested against only one bacterial strain. No in vivo testing was performed. The use of chloroform as a manufacturing solvent raises questions about residual solvent safety. The study focused on manufacturing optimization rather than therapeutic efficacy. No release kinetics data was reported."},{"rthcId":"RPEP-09131","title":"Lymphatic uptake of the lipidated and non-lipidated GLP-1 agonists liraglutide and exenatide is similar in rats.","authors":"Reddiar, Sanjeevini Babu; Abdallah, Mohammad; Styles, Ian K; Müllertz, Olivia O; Trevaskis, Natalie L","year":2024,"journal":"European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 200, 114339","doi":"10.1016/j.ejpb.2024.114339","pmid":"38789061","tags":["liraglutide","exenatide","bioavailability","glp-1"],"studyType":"animal pharmacokinetic","evidenceStrength":"moderate","keyFinding":"After subcutaneous injection in rats:\n- Liraglutide: apparent half-life 9.1 hours, delayed peak plasma levels, bioavailability ~10%\n- Exenatide: half-life ~1 hour, bioavailability ~100%\n\nLymphatic uptake was low for both peptides (<0.5% of dose), though lymph-to-plasma concentration ratios exceeded 1 at several early timepoints, suggesting some direct lymph uptake. The single-chain C16 palmitic acid on liraglutide did not substantially boost lymphatic transport.\n\nThe authors suggest that if lymphatic delivery is desired, more lipophilic conjugates (like diacylglycerols) with higher albumin or lipoprotein binding would be needed.","whyItMatters":"Lipidation is widely used to extend peptide drug half-lives, but the mechanism has been debated. Is it mainly albumin binding, or does lymphatic transport play a role? This study shows that a single C16 fatty acid (like on liraglutide) does not substantially boost lymphatic uptake. This has implications for designing the next generation of long-acting peptide drugs.","specificNumbers":"- Liraglutide half-life: 9.1 hours vs exenatide 1 hour\n- Liraglutide bioavailability: ~10% vs exenatide ~100%\n- Lymphatic uptake: <0.5% of dose for both\n- Lymph:plasma ratio >1 at early timepoints\n- Liraglutide lipid: single C16 palmitic acid chain","methodology":"Pharmacokinetic study in rats comparing subcutaneous administration of liraglutide (lipidated GLP-1 agonist) and exenatide (non-lipidated GLP-1 agonist). Measured plasma concentrations, lymph concentrations, lymph-to-plasma ratios, apparent half-lives, and bioavailability. Lymph was collected via thoracic lymph duct cannulation.","limitations":"Tested in rats only. Rat lymphatic physiology differs from humans. The thoracic duct cannulation procedure itself may alter lymphatic flow. Only two peptides were compared. The C16 palmitic acid on liraglutide is a relatively modest lipid modification. More lipophilic conjugates might show different lymphatic behavior."},{"rthcId":"RPEP-09132","title":"The impact of the migraine treatment onabotulinumtoxinA on inflammatory and pain responses: Insights from an animal model.","authors":"Reducha, Philip Victor; Bömers, Jesper Peter; Edvinsson, Lars; Haanes, Kristian Agmund","year":2024,"journal":"Headache, 64(6), 652-662","doi":"10.1111/head.14726","pmid":"38700141","tags":["neuropeptides","pain"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"CFA-induced facial inflammation increased periorbital mechanical sensitivity. The inflamed side showed greater sensitivity than other periorbital areas.\n\nBotox pretreatment reduced baseline CGRP release under CFA-inflamed conditions, suggesting it dampens ongoing CGRP secretion. However, it did not reduce pain sensitivity in the von Frey test, and it did not alter stimulated CGRP release.\n\nSNAP-25 analysis in the trigeminal ganglion showed both intact and cleaved forms elevated in Botox-treated animals. SNAP-25 cleavage is the hallmark of Botox's mechanism: it disrupts the protein machinery needed for neurotransmitter release.","whyItMatters":"Botox is FDA-approved for chronic migraine and is thought to work partly by reducing CGRP release. This study provides mechanistic evidence: Botox does reduce baseline CGRP under inflammatory conditions. But the failure to reduce pain sensitivity suggests Botox's clinical benefit in migraine involves more than just CGRP suppression.","specificNumbers":"- Botox given periorbital 3 days before CFA inflammation\n- Reduced baseline CGRP release under inflamed conditions\n- Elevated both intact and cleaved SNAP-25 in trigeminal ganglion\n- Did not reduce pain sensitivity in von Frey test\n- Did not alter stimulated CGRP release","methodology":"Botox or control was given subcutaneously at the periorbital region of rats 3 days before CFA-induced inflammation. Periorbital mechanical sensitivity was measured with electronic von Frey testing. CGRP release was measured from trigeminal tissue. SNAP-25 levels (intact and cleaved) were measured by Western blot in the trigeminal ganglion.","limitations":"This is a CFA inflammation model in rats, not a migraine model. The periorbital inflammation may not replicate migraine pathophysiology. Pain measurement relied on mechanical sensitivity, which may not capture all aspects of migraine-related pain. The timing of Botox administration (3 days before inflammation) may not match clinical practice. Small animal studies have limited statistical power."},{"rthcId":"RPEP-09133","title":"Research priorities for randomised controlled trials in chronic migraine preventive medication: A stakeholder consensus workshop.","authors":"Rees, Sophie; Cooklin, Andrew; Duncan, Callum; Matharu, Manjit; Naghdi, Seyran; Underwood, Martin; Mistry, Hema","year":2024,"journal":"NIHR open research, 4, 16","doi":"10.3310/nihropenres.13548.2","pmid":"41059134","tags":["neuropeptides","pain","clinical-trials"],"studyType":"consensus workshop","evidenceStrength":"not applicable","keyFinding":"Using nominal group technique (a structured consensus method), the stakeholders identified their research priorities:\n\n1. Top priority: Comparing CGRP monoclonal antibodies to onabotulinumtoxinA (Botox)\n2. High priority: Candesartan vs placebo\n3. High priority: Flunarizine vs placebo\n4. Also discussed: Combining CGRP antibodies with other medications\n\nThe group noted that despite multiple available chronic migraine preventives, high-quality head-to-head randomized evidence is scarce. Most drugs were tested only against placebo, making it hard for clinicians and patients to choose between options.","whyItMatters":"Chronic migraine affects about 2% of the global population. Multiple preventive treatments exist (Botox, CGRP antibodies, topiramate, amitriptyline, candesartan, flunarizine) but doctors have little evidence to guide which to try first. This patient-clinician consensus highlights the most urgent evidence gaps from the perspective of those most affected.","specificNumbers":"- 8 chronic migraine patients participated\n- 11 healthcare professionals participated\n- Top priority: CGRP mAbs vs onabotulinumtoxinA\n- Drug priorities vs placebo: candesartan and flunarizine\n- Chronic migraine: headaches on ≥15 days per month","methodology":"Online consensus workshop using nominal group technique, a structured approach where participants independently generate ideas, share them, discuss, and rank priorities through voting. Eight people with chronic migraine and eleven healthcare professionals participated.","limitations":"Small sample size (19 participants). UK-based, so priorities may differ in other healthcare systems. Nominal group technique produces consensus but may not represent the full range of patient and clinician perspectives. The workshop format limits deep exploration of any single topic. Funding for the identified trials is not guaranteed."},{"rthcId":"RPEP-09134","title":"Tirzepatide, GIP(1-42) and GIP(1-30) display unique signaling profiles at two common GIP receptor variants, E354 and Q354.","authors":"Rees, Tayla A; Buttle, Benjamin J; Tasma, Zoe; Yang, Sung-Hyun; Harris, Paul W R; Walker, Christopher S","year":2024,"journal":"Frontiers in pharmacology, 15, 1463313","doi":"10.3389/fphar.2024.1463313","pmid":"39464637","tags":["tirzepatide","glp-1","receptor-signaling"],"studyType":"in vitro","evidenceStrength":"moderate","keyFinding":"Tirzepatide showed biased agonism at the GIP receptor, meaning it preferentially activated the Gαs/cAMP pathway while having weaker effects on IP1 accumulation, AKT, ERK1/2, and CREB phosphorylation. This bias was consistent at both the wild-type (E354) and E354Q GIP receptor variants.\n\nThe natural GIP peptides GIP(1-42) and GIP(1-30)NH2 were generally equipotent across pathways, with one exception: GIP(1-30)NH2 was more potent than GIP(1-42) for CREB phosphorylation at the E354Q variant.\n\nThe E354Q variant is clinically relevant because it is associated with increased type 2 diabetes risk and lower body mass index. Understanding how drugs and natural peptides signal differently at this variant could help explain these clinical associations.","whyItMatters":"Tirzepatide is clinically more effective than pure GLP-1 drugs, but the reasons are not fully understood. This study reveals that tirzepatide's GIP receptor activity is biased toward cAMP, which could explain its unique pharmacological profile. The E354Q variant affects millions of people and may influence individual responses to tirzepatide.","specificNumbers":"- GIP receptor variants studied: E354 (wild-type) and E354Q\n- Signaling pathways: cAMP, IP1, AKT, ERK1/2, CREB phosphorylation\n- Tirzepatide: biased toward cAMP at both variants\n- GIP(1-42) and GIP(1-30)NH2: generally equipotent across pathways\n- E354Q variant: associated with T2D risk and lower BMI","methodology":"Researchers expressed wild-type (E354) and E354Q GIP receptors in Cos7 cells. They tested GIP(1-42), GIP(1-30)NH2, and tirzepatide across five signaling pathways: cAMP accumulation, IP1 accumulation, AKT phosphorylation, ERK1/2 phosphorylation, and CREB phosphorylation. Dose-response curves were generated for each drug at each receptor variant.","limitations":"This was done in Cos7 cells (monkey kidney cells) that do not naturally express GIP receptors. Overexpression systems may not replicate native receptor signaling. The study used only three agonists. In vivo, tirzepatide acts on both GIP and GLP-1 receptors simultaneously, and this study only looked at GIP receptor signaling in isolation. The clinical significance of the signaling bias is inferred, not directly tested."},{"rthcId":"RPEP-09135","title":"Tirzepatide modulates the regulation of adipocyte nutrient metabolism through long-acting activation of the GIP receptor.","authors":"Regmi, Ajit; Aihara, Eitaro; Christe, Michael E; Varga, Gabor; Beyer, Thomas P; Ruan, Xiaoping; Beebe, Emily; O'Farrell, Libbey S; Bellinger, Melissa A; Austin, Aaron K; Lin, Yanzhu; Hu, Haitao; Konkol, Debra L; Wojnicki, Samantha; Holland, Adrienne K; Friedrich, Jessica L; Brown, Robert A; Estelle, Amanda S; Badger, Hannah S; Gaidosh, Gabriel S; Kooijman, Sander; Rensen, Patrick C N; Coskun, Tamer; Thomas, Melissa K; Roell, William","year":2024,"journal":"Cell metabolism, 36(7), 1534-1549.e7","doi":"10.1016/j.cmet.2024.05.010","pmid":"38878772","tags":["tirzepatide","glp-1","weight-loss","receptor-signaling"],"studyType":"in vitro/animal","evidenceStrength":"strong","keyFinding":"In human adipocytes (fat cells):\n- With insulin present: GIP receptor activation enhanced insulin signaling, boosted glucose uptake, and increased conversion of glucose to glycerol (for fat storage)\n- Without insulin: GIP receptor activation increased lipolysis (fat breakdown and release)\n\nIn diet-induced obese mice treated with a long-acting GIP receptor agonist:\n- Reduced circulating triglyceride levels during oral lipid challenge\n- Increased lipoprotein-derived fatty acid uptake into adipose tissue\n\nThis dual action (storing fat when fed, releasing fat when fasting) explains how GIP activation can simultaneously improve blood lipids while supporting proper fat tissue function.","whyItMatters":"Tirzepatide is more effective than pure GLP-1 drugs for weight loss and metabolic improvement, but the role of its GIP component has been controversial. Some researchers thought GIP would worsen obesity because it promotes fat storage. This study resolves the paradox: GIP's effect depends on insulin levels. It stores fat appropriately after meals (clearing lipids from blood) and releases fat during fasting (providing energy). This is healthy metabolic flexibility.","specificNumbers":"- GIP + insulin: enhanced glucose uptake and glucose-to-glycerol conversion\n- GIP alone: increased lipolysis\n- Obese mice: reduced circulating triglycerides during lipid challenge\n- Obese mice: increased fatty acid uptake into adipose tissue","methodology":"Researchers used human adipocytes in functional assays to measure insulin signaling, glucose uptake, glucose-to-glycerol conversion, and lipolysis under varying insulin conditions. In vivo studies used diet-induced obese mice treated with a long-acting GIP receptor agonist, measuring circulating triglycerides during oral lipid challenge and fatty acid uptake into adipose tissue.","limitations":"The human fat cell experiments were in vitro and may not fully represent in vivo adipose tissue behavior. The mouse experiments used a GIP receptor agonist alone, not tirzepatide (which also activates GLP-1 receptors). The cooperative effects with GLP-1 signaling were not studied. Long-term effects of chronic GIP receptor activation on fat tissue are unknown."},{"rthcId":"RPEP-09136","title":"Efficacy and safety of semaglutide in patients with heart failure with preserved ejection fraction and obesity.","authors":"Rehman, Ayesha; Saidullah, Shahab; Asad, Muhammad; Gondal, Umer R; Ashraf, Amna; Khan, Muhammad F; Akhtar, Waheed; Mehmoodi, Amin; Malik, Jahanzeb","year":2024,"journal":"Clinical cardiology, 47(5), e24283","doi":"10.1002/clc.24283","pmid":"38767042","tags":["semaglutide","cardiovascular","weight-loss","glp-1"],"studyType":"retrospective cohort","evidenceStrength":"moderate","keyFinding":"Semaglutide produced significant improvements in patients with HFpEF and obesity:\n- 6-minute walk distance: improved by 15.1 meters vs placebo (95% CI 5.8-24.4, p = 0.002)\n- Body weight: reduced by 2.9% vs placebo (95% CI -4.1 to -1.7, p = 0.001)\n- C-reactive protein: reduced (indicating lower inflammation)\n- Several secondary clinical endpoints also improved\n- Adverse events: generally well-tolerated with no unexpected safety concerns","whyItMatters":"HFpEF with obesity is one of the fastest-growing heart failure phenotypes. Obesity worsens heart stiffness, exercise intolerance, and quality of life. Traditional heart failure drugs have limited benefit in HFpEF. Semaglutide addresses both the obesity and inflammation components, offering a mechanistic match for this specific patient population.","specificNumbers":"- 318 patients (104 semaglutide, 214 placebo)\n- 6-min walk distance: +15.1 meters (95% CI 5.8-24.4, p = 0.002)\n- Weight change: -2.9% vs placebo (95% CI -4.1 to -1.7, p = 0.001)\n- C-reactive protein: reduced\n- No unexpected safety concerns","methodology":"Retrospective study analyzing 318 HFpEF patients with obesity. 104 received semaglutide, 214 received placebo. Primary endpoints were changes in exercise capacity (6-minute walk distance) and weight management. Secondary endpoints included CRP levels and other clinical parameters.","limitations":"This was a retrospective study, not a prospective randomized trial. The allocation to semaglutide vs placebo groups in a retrospective design raises questions about selection bias. The 15-meter improvement in 6-minute walk distance, while statistically significant, is modest. The study does not report heart failure hospitalization or mortality outcomes. CRP reduction does not necessarily translate to clinical benefit."},{"rthcId":"RPEP-09137","title":"Assessing the Renal Outcomes of Semaglutide in Diabetic Kidney Disease: A Systematic Review.","authors":"Rehman, Shuja Ur; Kolanu, Nikhil Deep; Mushtaq, Muhammad Muaz; Ali, Husnain; Ahmed, Zeeshan; Mushtaq, Maham; Liaqat, Maryyam; Sarwer, Muhammad Asad; Bokhari, Syed Faqeer Hussain; Ahmed, Fazeel; Bakht, Danyal","year":2024,"journal":"Cureus, 16(7), e64038","doi":"10.7759/cureus.64038","pmid":"39114239","tags":["semaglutide","kidney","diabetes","glp-1","side-effects"],"studyType":"systematic review","evidenceStrength":"moderate","keyFinding":"Albuminuria was more consistently reduced by semaglutide than eGFR. The benefit was strongest in patients with macroalbuminuria (heavy protein loss). This suggests semaglutide may help slow the progression of diabetic kidney disease by reducing the protein that damages kidney filters.\n\nHowever, the impact on eGFR was variable. Some studies showed improvement, others showed no change, and some showed decrease. This inconsistency could reflect differences in patient populations, disease severity, and follow-up duration.\n\nTwo case reports described acute kidney injury (AKI) associated with semaglutide, including one case of acute interstitial nephritis. This highlights the need for kidney monitoring during therapy, particularly in patients with advanced chronic kidney disease.","whyItMatters":"Diabetic kidney disease is the leading cause of kidney failure worldwide. Semaglutide's ability to reduce albuminuria is promising because albuminuria drives kidney damage progression. The FLOW trial (published separately) showed semaglutide reduced hard kidney outcomes by 24%. This review provides additional context about which kidney parameters improve and which patients may be at risk.","specificNumbers":"- 6 studies included (2 case reports, 4 cohorts)\n- Albuminuria: consistently reduced, especially macroalbuminuria\n- eGFR: variable results across studies\n- AKI: 2 case reports of acute kidney injury\n- 1 case of acute interstitial nephritis\n- Semaglutide: improved glycemic control and weight in all studies","methodology":"Systematic review searching for all published evidence on semaglutide's renal effects in diabetic kidney disease. Six eligible studies were identified: 2 case reports and 4 cohort studies from diverse geographic locations. Primary outcomes were eGFR changes and albuminuria. Secondary outcomes included AKI incidence and other renal biomarkers.","limitations":"Only 6 studies were found, and most were small cohorts or case reports. No randomized controlled trials were included (the FLOW trial was published separately). The case reports of AKI may represent rare events or confounded situations. The variable eGFR results could reflect the normal trajectory of diabetic kidney disease rather than drug effects. Geographic diversity may introduce confounding from different healthcare practices."},{"rthcId":"RPEP-09138","title":"Liposome nanoparticle conjugation and cell penetrating peptide sequences (CPPs) enhance the cellular delivery of the tau aggregation inhibitor RI-AG03.","authors":"Reich, Niklas; Parkin, Edward; Dawson, Neil","year":2024,"journal":"Journal of cellular and molecular medicine, 28(11), e18477","doi":"10.1111/jcmm.18477","pmid":"38853458","tags":["cell-penetrating","peptide-delivery","neuroprotection"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Liposome conjugation of CPP-containing RI-AG03 peptides increased cellular association three-fold compared to unconjugated liposomes. Both polyR (polyarginine) and TAT cell-penetrating sequences achieved this enhancement.\n\nInhibition of macropinocytosis reduced uptake of unconjugated and RI-AG03-polyR-linked liposomes, but had no effect on RI-AG03-TAT-conjugated liposome uptake, suggesting different internalization routes.\n\nRI-AG03-polyR showed co-localization with macropinosomes and lysosomes. Importantly, RI-AG03-polyR detached from liposomes after cellular uptake, largely evading organellar entrapment. This is critical because drugs trapped in lysosomes are degraded and never reach their targets.","whyItMatters":"Tau aggregation is a hallmark of Alzheimer's disease. Tau aggregates form inside cells, so any tau-blocking drug must get inside cells to work. This study shows that liposome-CPP systems can deliver the tau inhibitor peptide into cells with three times higher efficiency, and the peptide avoids lysosomal degradation by detaching from the carrier once inside.","specificNumbers":"- CPP-linked liposomes: 3x higher cellular uptake\n- Both polyR and TAT sequences effective\n- Macropinocytosis: involved in polyR but not TAT uptake\n- RI-AG03-polyR: detached from liposomes inside cells\n- Lysosomal escape: peptide largely avoided organellar entrapment","methodology":"Researchers tested free RI-AG03, liposome-conjugated RI-AG03, and liposome-conjugated RI-AG03 with polyR or TAT CPP sequences. Cellular uptake was measured by fluorescence. Uptake mechanisms were probed with macropinocytosis inhibitors. Intracellular trafficking was visualized with co-localization microscopy. Peptide detachment from liposomes was confirmed inside cells.","limitations":"In vitro cell culture study only. No animal model testing. The cells used may not represent the blood-brain barrier or neuronal cells that are the actual targets. Liposome-CPP systems face challenges in vivo including immune clearance, off-target uptake, and difficulty crossing the blood-brain barrier. Whether RI-AG03 actually inhibits tau aggregation inside cells was not tested in this study."},{"rthcId":"RPEP-09139","title":"Prenatal ethanol and cannabis exposure have sex- and region-specific effects on somatostatin and neuropeptide Y interneurons in the rat hippocampus.","authors":"Reid, Hannah M O; Trepanier, Owen; Gross, Allyson; Poberezhnyk, Polina; Snowden, Taylor; Conway, Kate; Breit, Kristen R; Rodriguez, Cristina; Thomas, Jennifer D; Christie, Brian R","year":2024,"journal":"Alcohol, clinical & experimental research, 48(7), 1289-1301","doi":"10.1111/acer.15350","pmid":"38789401","tags":["neuropeptides","neuroprotection"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Prenatal THC exposure had region-specific and sex-specific effects on inhibitory interneurons in the hippocampus:\n- Female-specific decrease in NPY neuron density in the CA1 region after THC exposure\n- Somatostatin neurons were altered by THC in a region-specific and sex-specific manner\n- Combined alcohol + THC: reduced NPY neurons in the ventral dentate gyrus\n- Co-exposure did NOT produce additive or synergistic effects in other hippocampal areas\n\nThese findings build on the group's previous work showing prenatal substance exposure alters parvalbumin interneurons, extending the picture to two additional inhibitory cell types.","whyItMatters":"Cannabis use during pregnancy is increasing as legalization spreads. The hippocampus is critical for memory and emotional regulation. If prenatal THC disrupts inhibitory interneurons (NPY and somatostatin neurons), it could impair the brain's ability to regulate neural activity, potentially contributing to learning, memory, and mood problems in offspring.","specificNumbers":"- Exposure period: gestational days 5-20\n- Analysis at: postnatal day 70\n- NPY decrease: female CA1 region (THC exposure)\n- NPY decrease: ventral dentate gyrus (combined THC + alcohol)\n- Somatostatin: region-specific and sex-specific changes with THC\n- No additive/synergistic effects in most hippocampal areas","methodology":"2 × 2 design: pregnant Sprague-Dawley rats exposed to ethanol or air AND THC or vehicle during gestational days 5-20. Offspring were sacrificed at postnatal day 70. Immunohistochemistry for somatostatin and NPY neurons was performed on 50 μm hippocampal tissue sections.","limitations":"This was tested in rats. Human prenatal cannabis exposure involves different doses, timing, and genetic backgrounds. THC was given by inhalation, which may not exactly match human smoking patterns. The study measured neuron density at one time point (day 70), not developmental trajectory. Behavioral consequences of the interneuron changes were not tested. The 2×2 design had limited power for detecting interaction effects."},{"rthcId":"RPEP-09140","title":"Evolution of neuropeptide Y/RFamide-like receptors in nematodes.","authors":"Reinhardt, Franziska; Kaiser, Anette; Prömel, Simone; Stadler, Peter F","year":2024,"journal":"Heliyon, 10(14), e34473","doi":"10.1016/j.heliyon.2024.e34473","pmid":"39130429","tags":["neuropeptides","receptor-signaling","peptide-design"],"studyType":"computational/genomics","evidenceStrength":"moderate","keyFinding":"Using an automated computational pipeline based on ExonMatchSolver, researchers identified 1,557 NPY/RFamide-like receptors across 159 nematode genomes: 1,100 NPR-type, 375 FRPR-type, and 82 C09F12.3-type receptors.\n\nThe receptor family is generally well-conserved across the nematode phylum, suggesting these receptors play essential roles. However, no other genus shares all receptors with Caenorhabditis, and there are extensive clade-specific duplications and losses. This means different nematode species have evolved unique receptor repertoires, likely adapting NPY signaling to their specific ecological niches.","whyItMatters":"NPY/RFamide receptors control fundamental behaviors in nematodes: movement, feeding, and reproduction. Understanding how these receptors evolved across nematode species could help develop new anthelmintic (anti-worm) drugs by identifying conserved drug targets. Some nematode species are devastating human and agricultural parasites.","specificNumbers":"- 159 nematode genomes surveyed\n- 1,557 NPY/RFamide-like receptors identified\n- 1,100 NPR-type receptors\n- 375 FRPR-type receptors\n- 82 C09F12.3-type receptors\n- 41 known receptors in C. elegans as starting queries","methodology":"Researchers used sequences of selected receptor paralogs from C. elegans as queries and searched 159 representative nematode target genomes. They employed an automated pipeline using ExonMatchSolver for paralog-to-contig assignment and subclass-specific hidden Markov models for receptor detection and classification.","limitations":"Computational analysis depends on genome assembly quality, which varies across species. Some receptors may be missed due to incomplete genomes or gene annotation errors. The analysis identifies gene sequences but does not confirm protein expression or function. Functional validation of predicted receptors was not performed."},{"rthcId":"RPEP-09141","title":"Sodium-glucose cotransporter-2 inhibitor (SGLT2i) plus glucagon-like peptide type 1 receptor combination is more effective than SGLT2i plus dipeptidyl peptidase-4 inhibitor combination in treating obese mice metabolic dysfunction-associated steatotic liver disease (MASLD).","authors":"Reis-Barbosa, Pedro H; Mandarim-de-Lacerda, Carlos A","year":2024,"journal":"Fundamental & clinical pharmacology, 38(6), 1059-1068","doi":"10.1111/fcp.13024","pmid":"38923017","tags":["dulaglutide","glp-1","liver","diabetes"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"High-fat diet versus control: liver triglycerides increased 82%, steatosis increased 850%, glucose intolerance increased 71%, insulin increased 98%, and insulin resistance increased 68%.\n\nBoth drug combinations improved all parameters compared to untreated obese mice:\n- Empagliflozin + linagliptin: glucose intolerance -60%, insulin -61%, insulin resistance -46%, TAG -61%, steatosis -58%\n- Empagliflozin + dulaglutide: glucose intolerance -71%, insulin -58%, insulin resistance -62%, TAG -61%, steatosis -82%\n\nPrincipal component analysis clearly separated the groups: the GLP-1 combination was furthest from the disease group, while the DPP-4 combination fell between control and the GLP-1 group.","whyItMatters":"Fatty liver disease affects 25% of the global population and over half of people with type 2 diabetes. Single-drug treatment is often insufficient. This study compares two realistic combination strategies and shows the GLP-1 combination is clearly superior. This informs clinical decision-making about which drugs to combine for diabetes patients with fatty liver.","specificNumbers":"- 40 mice (10 per group, 4 groups)\n- Diet duration: 12 weeks high-fat\n- Treatment duration: 3 weeks\n- E+D vs HF: steatosis -82%, insulin resistance -62%, glucose intolerance -71%, TAG -61%\n- E+L vs HF: steatosis -58%, insulin resistance -46%, glucose intolerance -60%, TAG -61%\n- PCA placed E+D opposite from HF (disease group)","methodology":"Male C57BL/6J mice (3 months old) were fed control or high-fat diet for 12 weeks. Then treated for 3 additional weeks: control, high-fat untreated, high-fat + empagliflozin + linagliptin, or high-fat + empagliflozin + dulaglutide. 10 mice per group. Outcomes: liver triglycerides, steatosis histology, glucose tolerance, insulin levels, and gene expression for metabolism and mitochondrial biogenesis.","limitations":"Tested in mice, not people. Only 3 weeks of treatment, which is short even for mice. The high-fat diet model creates MASLD but may not replicate all features of human disease. Dulaglutide and linagliptin were compared at standard doses, but dose equivalency across drug classes is difficult in animals. Gene expression changes were measured but functional validation was not performed."},{"rthcId":"RPEP-09142","title":"The dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonist tirzepatide effects on body weight evolution, adiponectin, insulin and leptin levels in the combination of obesity, type 2 diabetes and menopause in mice.","authors":"Reis-Barbosa, Pedro H; Marcondes-de-Castro, Ilitch; Marinho, Thatiany S; Aguila, Marcia Barbosa; Mandarim-de-Lacerda, Carlos A","year":2024,"journal":"Diabetes, obesity & metabolism, 26(10), 4613-4621","doi":"10.1111/dom.15820","pmid":"39113264","tags":["tirzepatide","weight-loss","diabetes","hormone-optimization"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"The triple-challenge model (obesity + diabetes + ovariectomy) created the most severe metabolic dysfunction. Obese diabetic ovariectomized mice had more pronounced weight gain slopes than obese diabetic mice with intact ovaries.\n\nTirzepatide treatment produced negative allometric body weight slopes across treatment time, meaning weight declined consistently. Treated mice showed improved adiponectin (a beneficial fat hormone), insulin levels, and leptin levels. The drug effects were seen in both ovariectomized and sham groups.\n\nInteractions were observed between diet × ovariectomy (affecting weight gain), diet × tirzepatide (affecting weight loss), and diet × ovariectomy × tirzepatide (affecting food intake).","whyItMatters":"Menopausal women are at high risk for obesity, insulin resistance, and type 2 diabetes due to estrogen loss. This triple-challenge model is more clinically relevant than simple obesity models. Showing that tirzepatide works even with the added challenge of estrogen loss suggests it could be particularly valuable for postmenopausal women with diabetes.","specificNumbers":"- 120 mice across multiple groups\n- Diet: 12 weeks high-fat/high-sucrose\n- Treatment: tirzepatide 10 nmol/kg SC daily for 4 weeks\n- Tirzepatide: negative allometric body weight slopes (consistent weight loss)\n- Improved: adiponectin, insulin, leptin levels\n- Ovariectomy worsened weight gain beyond diet alone","methodology":"Female C57BL/6 mice (3 months old) underwent bilateral ovariectomy or sham surgery. For 12 weeks, groups received control diet or high-fat/high-sucrose diet (120 mice total across groups). Then tirzepatide (10 nmol/kg subcutaneously daily) or vehicle was administered for 4 additional weeks. Allometric analysis was used to model body weight changes over time.","limitations":"This was tested in mice. Ovariectomy in young mice does not perfectly model human menopause, which involves gradual hormonal changes over years. The tirzepatide dose (10 nmol/kg daily) may not directly translate to human dosing. Only 4 weeks of treatment was tested. The allometric analysis is useful for modeling weight trends but does not capture all metabolic endpoints. Human menopause involves more complex hormonal changes than simple estrogen loss."},{"rthcId":"RPEP-09143","title":"The Effect of Calcitonin Gene-Related Peptide Monoclonal Antibodies on Quality of Life among Migraine Patients: Pilot Study at the Hospital of Lithuanian University of Health Sciences Kaunas Clinics.","authors":"Remenčiūtė, Monika; Varžaitytė, Greta; Žemgulytė, Gintarė","year":2024,"journal":"Acta medica Lituanica, 31(1), 81-91","doi":"10.15388/Amed.2024.31.1.12","pmid":"38978850","tags":["cgrp","migraine"],"studyType":"cohort","evidenceStrength":"preliminary","keyFinding":"CGRP monoclonal antibody treatment reduced monthly migraine days and improved quality of life in patients with frequent migraines over a 6-month follow-up period.","whyItMatters":"Frequent migraines can be debilitating, and many older preventive treatments have limited effectiveness. This real-world data adds to evidence that CGRP-targeting antibodies offer meaningful improvement for people who suffer from chronic migraines.","specificNumbers":"41 patients were included, all with 4 or more monthly migraine days lasting more than 3 months. Patients received fremanezumab 225 mg and were followed for 6 months.","methodology":"Prospective observational study following 41 migraine patients receiving CGRP monoclonal antibody treatment at a university hospital in Lithuania.","limitations":"This was a small pilot study with only 41 patients at a single hospital, without a placebo comparison group. Results may not generalize to other populations."},{"rthcId":"RPEP-09144","title":"Brain uptake pharmacokinetics of albiglutide, dulaglutide, tirzepatide, and DA5-CH in the search for new treatments of Alzheimer's and Parkinson's diseases.","authors":"Rhea, Elizabeth M; Babin, Alice; Thomas, Peter; Omer, Mohamed; Weaver, Riley; Hansen, Kim; Banks, William A; Talbot, Konrad","year":2024,"journal":"Tissue barriers, 12(4), 2292461","doi":"10.1080/21688370.2023.2292461","pmid":"38095516","tags":["tirzepatide","glp-1-receptor-agonists","neuroprotection","peptide-delivery"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Tirzepatide had the highest rate of blood-brain barrier crossing among the four incretin receptor agonists tested, suggesting it may be the most promising for direct brain effects.","whyItMatters":"If incretin drugs can cross the blood-brain barrier, they might directly protect brain cells in diseases like Alzheimer's and Parkinson's. Knowing which drugs cross best helps prioritize which ones to study further.","specificNumbers":"Four drugs tested: albiglutide, dulaglutide, DA5-CH, and tirzepatide. Adult male CD-1 mice were used with radioactive labeling (125I or 14C).","methodology":"Researchers injected adult male mice with radioactively labeled versions of four drugs and measured brain uptake using multiple-time regression analysis.","limitations":"This was an animal study in mice, so brain uptake rates may differ in humans. The study measured how much drug reaches the brain but did not test whether it produces therapeutic effects there."},{"rthcId":"RPEP-09145","title":"Anti-obesity Drugs for the Treatment of Binge Eating Disorder: Opportunities and Challenges.","authors":"Riboldi, Ilaria; Carrà, Giuseppe","year":2024,"journal":"Alpha psychiatry, 25(3), 312-322","doi":"10.5152/alphapsychiatry.2024.241464","pmid":"39148594","tags":["glp-1-receptor-agonists","weight-loss","semaglutide","tirzepatide"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Anti-obesity drugs, particularly GLP-1 receptor agonists, may have potential for treating binge eating disorder, but current evidence is limited and the psychological components of BED require special attention.","whyItMatters":"Binge eating disorder is extremely common but has very few approved treatments. If obesity drugs can address both the weight and the eating behavior, it could help millions of people.","specificNumbers":"BED is described as the most prevalent form of disordered eating. Only lisdexamfetamine is currently approved for BED, and only in some countries.","methodology":"Narrative review of existing literature on anti-obesity drugs and their potential role in binge eating disorder treatment.","limitations":"This is a narrative review, not a systematic review or meta-analysis. Direct evidence for GLP-1 agonists in BED specifically is sparse."},{"rthcId":"RPEP-09146","title":"Suppression of cyclooxygenase-2 predisposes to heart failure with preserved ejection fraction.","authors":"Ricciotti, Emanuela; Haines, Philip G; Beerens, Manu; Kartoun, Uri; Castro, Cecilia; Tang, Soon Yew; Ghosh, Soumita; Das, Ujjalkumar S; Lahens, Nicholas F; Wang, Tao; Griffin, Jules L; Shaw, Stanley Y; MacRae, Calum A; FitzGerald, Garret A","year":2024,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2024.09.28.615616","pmid":"39651314","tags":["cardiovascular","peptide-safety"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Long-term COX-2 suppression caused diastolic dysfunction and features of HFpEF in aged female mice, while younger mice were unaffected.","whyItMatters":"Millions of people take NSAIDs regularly, and heart failure is a known risk. This study suggests that the risk may be specifically for HFpEF — a type of heart failure that is poorly understood and has few effective treatments.","specificNumbers":"The study used inducible COX-2 knockout mice. Aged female mice developed diastolic dysfunction; young mice and pharmacologically inhibited mice did not show acute effects.","methodology":"Genetic knockout and pharmacological inhibition of COX-2 in mice, comparing cardiac function across age groups and sexes.","limitations":"This is a mouse study, and the findings may not directly translate to humans. The sex-specific effect (females only) needs further investigation."},{"rthcId":"RPEP-09147","title":"Kidney effects of Glucagon-Like Peptide 1 (GLP1): from molecular foundations to a pharmacophysiological perspective.","authors":"Rico-Fontalvo, Jorge; Reina, Maricely; Soler, María José; Unigarro-Palacios, Mario; Castañeda-González, Juan Pablo; Quintero, Javier Jiménez; Raad-Sarabia, María; Moraes, Thyago Proença de; Daza-Arnedo, Rodrigo","year":2024,"journal":"Jornal brasileiro de nefrologia, 46(4), e20240101","doi":"10.1590/2175-8239-JBN-2024-0101en","pmid":"39514688","tags":["semaglutide","glp-1-receptor-agonists","kidney"],"studyType":"review","evidenceStrength":"strong","keyFinding":"GLP-1 receptor agonists protect kidneys through anti-inflammatory, antioxidant, and anti-fibrotic mechanisms, with clinical data from the FLOW trial confirming semaglutide slows kidney disease progression.","whyItMatters":"Chronic kidney disease affects hundreds of millions of people worldwide and has limited treatment options. Showing that GLP-1 drugs protect kidneys adds a major benefit beyond their effects on blood sugar and weight.","specificNumbers":"The FLOW study tested semaglutide 1 mg vs. placebo. Recruitment ran from 2019 to May 2021. GLP-1 drugs were first introduced for diabetes in 2005 and obesity in 2014.","methodology":"Pharmacophysiological review combining molecular mechanisms with clinical trial evidence.","limitations":"This is a review article synthesizing existing data. The kidney-protective mechanisms described are based partly on animal and cell studies."},{"rthcId":"RPEP-09148","title":"Glucagon-like peptide-1 (GLP-1) receptor agonists for weight management: A review for the gynecologic oncologist.","authors":"Riedinger, Courtney J; Sakach, Julia; Maples, Jill M; Fulton, Jessica; Chippior, Jessica; O'Donnell, Benjamin; O'Malley, David M; Chambers, Laura M","year":2024,"journal":"Gynecologic oncology, 190, 1-10","doi":"10.1016/j.ygyno.2024.07.008","pmid":"39116625","tags":["glp-1-receptor-agonists","weight-loss","cancer"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"GLP-1 receptor agonists produce significant weight loss and may reduce obesity-related risk factors for gynecologic cancers, though direct cancer prevention evidence is still needed.","whyItMatters":"Obesity is one of the strongest risk factors for endometrial and other gynecologic cancers. If GLP-1 drugs can meaningfully reduce weight in these patients, they could become an important part of cancer risk reduction.","specificNumbers":"GLP-1RAs were developed for diabetes and extended to obesity treatment. They can produce significant weight loss in combination with lifestyle changes.","methodology":"Narrative review aimed at gynecologic oncology practitioners, summarizing GLP-1 drug mechanisms, efficacy, and clinical considerations.","limitations":"This is a review, not original research. Direct evidence linking GLP-1 use to reduced gynecologic cancer incidence is not yet available."},{"rthcId":"RPEP-09149","title":"Reporting Quality and Risk of Bias Analysis of Published RCTs Assessing Anti-CGRP Monoclonal Antibodies in Migraine Prophylaxis: A Systematic Review.","authors":"Rikos, Dimitrios; Vikelis, Michail; Dermitzakis, Emmanouil V; Soldatos, Panagiotis; Rallis, Dimitrios; Rudolf, Jobst; Andreou, Anna P; Argyriou, Andreas A","year":2024,"journal":"Journal of clinical medicine, 13(7)","doi":"10.3390/jcm13071964","pmid":"38610729","tags":["cgrp","migraine"],"studyType":"meta-analysis","evidenceStrength":"moderate","keyFinding":"Published RCTs of anti-CGRP monoclonal antibodies for migraine have notable reporting quality gaps and potential biases beyond randomization.","whyItMatters":"Understanding the quality of clinical trial evidence helps doctors and patients make better-informed decisions about migraine treatments. Even well-known drugs deserve scrutiny of their evidence base.","specificNumbers":"The review covered phase II/III RCTs of anti-CGRP monoclonal antibodies for both episodic and chronic migraine, found through PubMed and EMBASE.","methodology":"Systematic review of phase II/III randomized controlled trials, assessed using PRISMA guidelines on PubMed and EMBASE databases.","limitations":"The review only assessed reporting quality and bias risk, not whether the drugs are effective. Some biases may be inherent to the trial designs used across the field."},{"rthcId":"RPEP-09150","title":"Bismuth-Cyclized Cell-Penetrating Peptides.","authors":"Ritchey, Jeremy L; Filippi, Lindsi; Ballard, Davis; Pei, Dehua","year":2024,"journal":"Molecular pharmaceutics, 21(10), 5255-5260","doi":"10.1021/acs.molpharmaceut.4c00688","pmid":"39223839","tags":["cell-penetrating-peptides","peptide-delivery","peptide-engineering"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Bismuth-cyclized cell-penetrating peptides showed improved cellular entry efficiency and metabolic stability compared to linear CPPs, without the epimerization issues of previous cyclization methods.","whyItMatters":"Getting drugs and research tools inside cells is a major challenge in medicine. Better cell-penetrating peptides could improve drug delivery for many conditions, from cancer to genetic diseases.","specificNumbers":"Not specified — this is a proof-of-concept study demonstrating the bismuth cyclization method.","methodology":"Laboratory development and testing of a novel peptide cyclization method using bismuth coordination chemistry.","limitations":"This is an early-stage laboratory study. The bismuth-cyclized peptides need to be tested in living organisms to confirm safety and effectiveness."},{"rthcId":"RPEP-09151","title":"Evaluating the safety profile of semaglutide: an updated meta-analysis.","authors":"Rivera, Frederick Berro; Arias-Aguirre, Eloise; Aguirre, Zedrick; Ybañez, Mc John C; Rubia, Janos Marc M; Galang, Danica Janine; Lumbang, Grace Nooriza; Ruyeras, Jade Monica Marie J; Magalong, John Vincent; Pine, Polyn Luz; Amigo, John Andrew C; Ansay, Marie Francesca M; Zelenkov, Nenad; Thomas, Steve Samuel; Vijayaraghavan, Krishnaswami","year":2024,"journal":"Current medical research and opinion, 40(9), 1495-1514","doi":"10.1080/03007995.2024.2383731","pmid":"39046272","tags":["semaglutide","peptide-safety","cardiovascular"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Semaglutide does not increase cardiovascular adverse events or mortality but is associated with higher rates of gastrointestinal side effects compared to placebo.","whyItMatters":"As semaglutide use expands rapidly for both diabetes and weight loss, having comprehensive safety data is critical for patients and doctors making treatment decisions.","specificNumbers":"Primary outcome was cardiovascular adverse events. Secondary outcomes included sudden cardiac death, adverse events leading to death, and gastrointestinal side effects.","methodology":"Meta-analysis of randomized controlled trials comparing semaglutide to placebo across various treatment durations and patient populations.","limitations":"The analysis is limited to randomized trial data, which may not capture rare side effects. Real-world safety may differ from trial populations."},{"rthcId":"RPEP-09152","title":"Glucagon-like peptide-1 receptor agonists modestly reduced blood pressure among patients with and without diabetes mellitus: A meta-analysis and meta-regression.","authors":"Rivera, Frederick Berro; Lumbang, Grace Nooriza O; Gaid, Danielle Rose Magno; Cruz, Linnaeus Louisse A; Magalong, John Vincent; Bantayan, Nathan Ross B; Lara-Breitinger, Kyla M; Gulati, Martha; Bakris, George","year":2024,"journal":"Diabetes, obesity & metabolism, 26(6), 2209-2228","doi":"10.1111/dom.15529","pmid":"38505997","tags":["glp-1-receptor-agonists","cardiovascular","blood-pressure"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"GLP-1 receptor agonists produce a modest but significant reduction in systolic blood pressure, potentially contributing to their cardiovascular protective effects.","whyItMatters":"High blood pressure is a leading cause of heart disease and stroke. Even small reductions in blood pressure across a large population can prevent many cardiovascular events.","specificNumbers":"Comprehensive database search through December 2023. Results reported as mean difference in mmHg using random effects modeling.","methodology":"Meta-analysis and meta-regression of placebo-controlled randomized controlled trials, using random effects modeling.","limitations":"Blood pressure was typically a secondary outcome in the included trials, not the primary focus. The reduction was described as modest."},{"rthcId":"RPEP-09153","title":"Peptide-Drug Conjugates: Design, Chemistry, and Drug Delivery System as a Novel Cancer Theranostic.","authors":"Rizvi, Syed Faheem Askari; Zhang, Linjie; Zhang, Haixia; Fang, Quan","year":2024,"journal":"ACS pharmacology & translational science, 7(2), 309-334","doi":"10.1021/acsptsci.3c00269","pmid":"38357281","tags":["peptide-drug-conjugates","cancer","peptide-delivery"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Peptide-drug conjugates represent a promising targeted cancer therapy approach, offering specificity, deeper tumor penetration, and simpler manufacturing compared to antibody-based delivery systems.","whyItMatters":"Traditional chemotherapy damages healthy cells along with cancer cells. PDCs aim to deliver drugs only to tumors, which could mean better treatment with fewer side effects.","specificNumbers":"Not applicable — comprehensive review of the PDC field and design principles.","methodology":"Comprehensive review of PDC design, chemistry, and drug delivery system applications in cancer theranostics.","limitations":"Most PDC data comes from preclinical studies. Clinical translation faces challenges including stability in the bloodstream and manufacturing scale-up."},{"rthcId":"RPEP-09154","title":"Real-World Impact of GLP-1 Receptor Agonists on Endoscopic Patient Outcomes in an Ambulatory Setting: A Retrospective Study at a Large Tertiary Center.","authors":"Robalino Gonzaga, Ernesto; Farooq, Aimen; Mohammed, Abdul; Chandan, Saurabh; Fawwaz, Baha; Singh, Gurdeep; Malik, Amna; Zhang, Yiyang; Kadkhodayan, Kambiz","year":2024,"journal":"Journal of clinical medicine, 13(18)","doi":"10.3390/jcm13185403","pmid":"39336890","tags":["glp-1-receptor-agonists","peptide-safety"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"GLP-1 receptor agonist use was not associated with increased risk of aspiration or retained gastric contents during outpatient upper endoscopy.","whyItMatters":"Millions of people take GLP-1 drugs, and many will need endoscopy at some point. This real-world data helps answer practical safety questions about whether patients need to stop their medication before the procedure.","specificNumbers":"Records from patients undergoing esophagogastroduodenoscopy (EGD) at a hospital-based outpatient center from January onward were reviewed.","methodology":"Retrospective review of electronic medical records from patients undergoing EGD at a hospital-based outpatient center.","limitations":"Retrospective study design limits the ability to draw definitive conclusions. The outpatient setting may not reflect higher-risk inpatient populations."},{"rthcId":"RPEP-09155","title":"Structural Consequences of Introducing Bioactive Domains to Designer β-Sheet Peptide Self-Assemblies.","authors":"Robang, Alicia S; Roy, Abhishek; Dodd-O, Joseph B; He, Dongjing; Le, Justin V; McShan, Andrew C; Hu, Yuhang; Kumar, Vivek A; Paravastu, Anant K","year":2024,"journal":"Biomacromolecules, 25(3), 1429-1438","doi":"10.1021/acs.biomac.3c00962","pmid":"38408372","tags":["peptide-engineering","self-assembling-peptides"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Bioactive domains attached to β-sheet self-assembling peptides can either remain solvent-accessible as intended or become incorporated into the β-sheet structure, depending on their specific properties.","whyItMatters":"Understanding how functional segments affect self-assembling peptide structures is critical for designing effective biomaterials for tissue engineering and drug delivery.","specificNumbers":"Not specified — structural characterization study using NMR techniques.","methodology":"Solid- and solution-state nuclear magnetic resonance (NMR) spectroscopy analysis of multidomain peptide assemblies.","limitations":"In vitro structural analysis that may not fully predict behavior in biological environments. Limited to the specific peptide sequences tested."},{"rthcId":"RPEP-09156","title":"Partly Substituting Whey for Collagen Peptide Supplementation Improves Neither Indices of Muscle Damage Nor Recovery of Functional Capacity During Eccentric Exercise Training in Fit Males.","authors":"Robberechts, Ruben; Poffé, Chiel; Ampe, Noémie; Bogaerts, Stijn; Hespel, Peter","year":2024,"journal":"International journal of sport nutrition and exercise metabolism, 34(2), 69-78","doi":"10.1123/ijsnem.2023-0070","pmid":"37922892","tags":["collagen-peptides","exercise-performance"],"studyType":"RCT","evidenceStrength":"moderate","keyFinding":"Partly replacing whey protein with collagen peptides (20g collagen + 25g whey vs. 45g whey alone) provided no additional benefit for muscle damage or functional recovery during eccentric exercise training.","whyItMatters":"Collagen peptides are heavily marketed for muscle and joint recovery. This study provides evidence that for fit individuals already consuming adequate protein, adding collagen peptides does not offer extra muscle recovery benefits.","specificNumbers":"20 g collagen peptides + 25 g whey protein vs. 45 g whey protein alone. Participants were young fit males doing eccentric exercise training.","methodology":"Randomized controlled trial comparing combined collagen-whey supplementation versus whey alone during eccentric exercise training in fit males.","limitations":"Only tested in young fit males, so results may differ in older adults or less trained individuals. The study used eccentric exercise specifically."},{"rthcId":"RPEP-09157","title":"Nonspecific oral medications versus anti-calcitonin gene-related peptide monoclonal antibodies for migraine: A systematic review and meta-analysis of randomized controlled trials.","authors":"Robblee, Jennifer; Hakim, Sameh M; Reynolds, John M; Monteith, Teshamae S; Zhang, Niushen; Barad, Meredith","year":2024,"journal":"Headache, 64(5), 547-572","doi":"10.1111/head.14693","pmid":"38634515","tags":["cgrp","migraine"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"CGRP monoclonal antibodies reduced monthly migraine days with effectiveness comparable to or exceeding topiramate and divalproex, with high certainty evidence.","whyItMatters":"Many migraine patients are forced to try and fail on older medications before getting access to CGRP antibodies. This evidence suggests that approach may delay effective treatment unnecessarily.","specificNumbers":"12 RCTs for CGRP mAbs, 5 for topiramate, and 3 for divalproex were included. Primary outcome: monthly migraine days or moderate-to-severe headache days.","methodology":"Systematic review and meta-analysis of class I/II randomized controlled trials comparing CGRP mAbs and nonspecific oral preventives versus placebo.","limitations":"Indirect comparison (both drug classes vs. placebo) rather than head-to-head trials. Differences in trial design and patient populations may affect comparisons."},{"rthcId":"RPEP-09158","title":"Assessing the immunogenicity risk of salmon calcitonin peptide impurities using in silico and in vitro methods.","authors":"Roberts, Brian J; Mattei, Aimee E; Howard, Kristina E; Weaver, James L; Liu, Hao; Lelias, Sandra; Martin, William D; Verthelyi, Daniela; Pang, Eric; Edwards, Katie J; De Groot, Anne S","year":2024,"journal":"Frontiers in pharmacology, 15, 1363139","doi":"10.3389/fphar.2024.1363139","pmid":"39185315","tags":["calcitonin","peptide-safety","peptide-engineering"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Certain synthesis-derived impurities of salmon calcitonin showed potential to bind HLA molecules and stimulate T cells, indicating immunogenicity risk that warrants monitoring.","whyItMatters":"As more peptide drugs shift from biological to chemical manufacturing, understanding whether new impurities can trigger immune reactions is essential for drug safety.","specificNumbers":"Impurities included amino acid insertions, deletions, and side-chain modifications from the synthesis process.","methodology":"Combined computational (in silico) prediction with in vitro HLA binding and T-cell stimulation assays to assess immunogenicity of peptide impurities.","limitations":"In silico and in vitro methods can predict immunogenicity risk but cannot confirm actual clinical immune reactions. In vivo validation would be needed."},{"rthcId":"RPEP-09159","title":"The Effect of Tirzepatide on Body Composition in People with Overweight and Obesity: A Systematic Review of Randomized, Controlled Studies.","authors":"Rochira, Vincenzo; Greco, Carla; Boni, Stefano; Costantino, Francesco; Dalla Valentina, Leonardo; Zanni, Eleonora; Itani, Leila; El Ghoch, Marwan","year":2024,"journal":"Diseases (Basel, Switzerland), 12(9)","doi":"10.3390/diseases12090204","pmid":"39329873","tags":["tirzepatide","weight-loss","body-composition"],"studyType":"meta-analysis","evidenceStrength":"moderate","keyFinding":"Tirzepatide consistently reduces fat mass in people with overweight or obesity, but the ratio of fat to lean mass loss varies and requires attention in clinical practice.","whyItMatters":"Weight loss drugs are most valuable when they primarily reduce fat while preserving muscle. Understanding tirzepatide's effect on body composition helps guide its clinical use and the need for exercise alongside treatment.","specificNumbers":"6 randomized controlled studies identified from 1,379 papers retrieved. Studies examined people with overweight or obesity (BMI ≥ various thresholds).","methodology":"Systematic review of 6 randomized controlled studies examining body composition changes with tirzepatide, following PRISMA guidelines.","limitations":"Only 6 studies met inclusion criteria, and body composition measurement methods varied across them. Limited data on long-term body composition effects."},{"rthcId":"RPEP-09160","title":"Role of gut-liver axis and glucagon-like peptide-1 receptor agonists in the treatment of metabolic dysfunction-associated fatty liver disease.","authors":"Rochoń, Jakub; Kalinowski, Piotr; Szymanek-Majchrzak, Ksenia; Grąt, Michał","year":2024,"journal":"World journal of gastroenterology, 30(23), 2964-2980","doi":"10.3748/wjg.v30.i23.2964","pmid":"38946874","tags":["glp-1-receptor-agonists","liver","gut-microbiome"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"GLP-1 receptor agonists may treat MAFLD through dual action on the gut-liver axis, reducing liver fat and inflammation while potentially improving gut microbiome balance.","whyItMatters":"Fatty liver disease affects about a quarter of the world's population and can progress to cirrhosis and liver cancer. Currently there are very few approved treatments, making GLP-1 drugs a promising option.","specificNumbers":"MAFLD is described as one of the most common liver diseases worldwide with increasing prevalence. Advanced cases can progress to fibrosis, cirrhosis, and hepatocellular carcinoma.","methodology":"Narrative review of the gut-liver axis in MAFLD pathogenesis and the role of GLP-1 receptor agonists in treatment.","limitations":"Narrative review without systematic methodology. Much of the gut microbiome evidence comes from animal studies."},{"rthcId":"RPEP-09161","title":"Kidney outcomes are altered by preconception weight modulation in rodent mothers with obesity.","authors":"Rodrigo, Natassia; Chen, Hui; Pollock, Carol A; Glastras, Sarah J","year":2024,"journal":"Scientific reports, 14(1), 17363","doi":"10.1038/s41598-024-68234-9","pmid":"39075112","tags":["liraglutide","glp-1-receptor-agonists","kidney"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Preconception weight loss through either diet modification or liraglutide treatment improved maternal kidney outcomes in late gestation in a mouse model of obesity.","whyItMatters":"Obesity-related kidney problems during pregnancy are a growing concern. Showing that preconception weight loss protects the kidneys gives doctors a clear intervention window.","specificNumbers":"C57BL/6 female mice were fed high-fat diet for 8 weeks. Weight loss was induced either by switching to chow diet or by liraglutide (a GLP-1 agonist).","methodology":"Animal study using C57BL/6 female mice fed high-fat diet for 8 weeks, then randomized to continued HFD, diet switch, or liraglutide before mating.","limitations":"This is a mouse study, and kidney responses during pregnancy may differ in humans. Liraglutide is not currently approved for preconception use."},{"rthcId":"RPEP-09162","title":"Long-Term Assessment of Weight Loss Medications in a Veteran Population.","authors":"Rodriguez, Allison D; Ifeachor, Amanda P; Moore, Emily A; Otte, Cassandra F; Schopper, M Joseph; Liangpunsakul, Suthat; Lteif, Amale A","year":2024,"journal":"Federal practitioner : for the health care professionals of the VA, DoD, and PHS, 41(7), 202-207","doi":"10.12788/fp.0490","pmid":"39411075","tags":["semaglutide","liraglutide","weight-loss"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Semaglutide and phentermine/topiramate showed the most consistent long-term weight loss among veterans, with data extending up to 48 months.","whyItMatters":"Most weight loss drug studies last 1-2 years. This study provides real-world data on how well these medications work over up to 4 years, which matters because obesity is a chronic condition.","specificNumbers":"Weight tracked at 3, 6, 12, 24, 36, and 48 months. Six medications compared: semaglutide, orlistat, liraglutide, phentermine, phentermine/topiramate, and naltrexone/bupropion.","methodology":"Single-center retrospective study analyzing weight outcomes at multiple timepoints for veterans prescribed various weight loss medications.","limitations":"Retrospective single-center study without randomization. Patients were not randomly assigned to medications, so differences between groups may reflect patient selection."},{"rthcId":"RPEP-09163","title":"Semaglutide vs Tirzepatide for Weight Loss in Adults With Overweight or Obesity.","authors":"Rodriguez, Patricia J; Goodwin Cartwright, Brianna M; Gratzl, Samuel; Brar, Rajdeep; Baker, Charlotte; Gluckman, Ty J; Stucky, Nicholas L","year":2024,"journal":"JAMA internal medicine, 184(9), 1056-1064","doi":"10.1001/jamainternmed.2024.2525","pmid":"38976257","tags":["tirzepatide","semaglutide","weight-loss"],"studyType":"cohort","evidenceStrength":"strong","keyFinding":"Tirzepatide produced greater on-treatment weight loss than semaglutide in adults with overweight or obesity in a real-world clinical setting, with comparable gastrointestinal side effect rates.","whyItMatters":"Patients and doctors have been waiting for head-to-head data comparing these two drugs. This real-world study provides the first large-scale direct comparison.","specificNumbers":"Adults with overweight or obesity identified from EHR data between May 2022 and September 2023. Both drugs were prescribed with type 2 diabetes labeling.","methodology":"Retrospective cohort study using electronic health records from a clinical setting, comparing adults receiving tirzepatide vs. semaglutide (both labeled for type 2 diabetes).","limitations":"This is an observational study, not a randomized trial. Patients were not randomly assigned, so underlying differences between groups may affect results. Both drugs were prescribed for T2D, not specifically for weight loss."},{"rthcId":"RPEP-09164","title":"Transforming body composition with semaglutide in adults with obesity and type 2 diabetes mellitus.","authors":"Rodríguez Jiménez, Beatriz; Rodríguez de Vera Gómez, Pablo; Belmonte Lomas, Samuel; Mesa Díaz, Ángel Manuel; Caballero Mateos, Irene; Galán, Irene; Morales Portillo, Cristóbal; Martínez-Brocca, María Asunción","year":2024,"journal":"Frontiers in endocrinology, 15, 1386542","doi":"10.3389/fendo.2024.1386542","pmid":"38894744","tags":["semaglutide","weight-loss","diabetes","body-composition"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Both oral and subcutaneous semaglutide significantly reduced fat mass and improved metabolic parameters in adults with obesity and type 2 diabetes over 24 weeks.","whyItMatters":"Knowing that semaglutide reduces fat specifically — not just total weight — is important because fat loss drives the metabolic health benefits, while muscle preservation maintains function and metabolism.","specificNumbers":"24-week study in adults with type 2 diabetes and BMI ≥ 30 kg/m². Both daily oral and weekly subcutaneous semaglutide were used. Body composition measured by bioelectrical impedance analysis.","methodology":"24-week quasi-experimental retrospective study using bioelectrical impedance analysis to measure body composition changes.","limitations":"Retrospective study design without randomization to oral versus subcutaneous groups. Bioelectrical impedance is less precise than DEXA scanning for body composition."},{"rthcId":"RPEP-09165","title":"Emerging roles of lipid and metabolic sensing in the neuroendocrine control of body weight and reproduction.","authors":"Rodríguez-Vázquez, Elvira; Aranda-Torrecillas, Álvaro; López-Sancho, María; Castellano, Juan M; Tena-Sempere, Manuel","year":2024,"journal":"Frontiers in endocrinology, 15, 1454874","doi":"10.3389/fendo.2024.1454874","pmid":"39290326","tags":["weight-loss","hormonal-peptides","receptor-signaling"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Lipid and metabolic sensing pathways in the hypothalamus coordinate both body weight regulation and reproductive function, with disruptions contributing to metabolic and fertility disorders.","whyItMatters":"Understanding how the brain links metabolism and fertility could lead to treatments that address both obesity and reproductive problems simultaneously.","specificNumbers":"Not applicable — mechanistic review article.","methodology":"Narrative review of neuroendocrine mechanisms linking metabolic sensing to weight and reproduction control in the hypothalamus.","limitations":"Review article synthesizing mostly preclinical data. Human applications are still largely theoretical."},{"rthcId":"RPEP-09166","title":"Recommendation for Clarifying FDA Policy in Evaluating \"Sameness\" of Higher Order Structure for Generic Peptide Therapeutics.","authors":"Rogers-Crovak, Jessica A; Delaney, Edward J; Detlefsen, David J","year":2024,"journal":"The AAPS journal, 27(1), 8","doi":"10.1208/s12248-024-00994-8","pmid":"39586870","tags":["semaglutide","liraglutide","peptide-engineering"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Current FDA guidance for evaluating generic peptide drug sameness needs clarification on higher order structure assessment to ensure generic peptide drugs are safe and effective.","whyItMatters":"As patents expire on blockbuster peptide drugs, millions of patients could benefit from cheaper generic versions — but only if those generics are truly equivalent to the originals.","specificNumbers":"The FDA issued final guidance in 2021. The market expansion is led by GLP-1 receptor agonists like semaglutide and liraglutide.","methodology":"Regulatory science commentary and recommendation paper analyzing FDA guidance on generic peptide drug evaluation.","limitations":"This is a policy recommendation paper, not a scientific study. The proposed clarifications have not yet been adopted by the FDA."},{"rthcId":"RPEP-09167","title":"Electrophysiological evaluation of the effect of peptide toxins on voltage-gated ion channels: a scoping review on theoretical and methodological aspects with focus on the Central and South American experience.","authors":"Rojas-Palomino, Jessica; Gómez-Restrepo, Alejandro; Salinas-Restrepo, Cristian; Segura, César; Giraldo, Marco A; Calderón, Juan C","year":2024,"journal":"The journal of venomous animals and toxins including tropical diseases, 30, e20230048","doi":"10.1590/1678-9199-JVATITD-2023-0048","pmid":"39263598","tags":["venom-peptides","ion-channels"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Patch-clamp electrophysiology is the most reliable method for assessing peptide toxin effects on ion channels, but is underutilized in Central and South American toxinology research due to technical and infrastructure barriers.","whyItMatters":"Venom-derived peptides are a rich source of potential drugs. Understanding their effects on ion channels is crucial for developing new pain treatments, antivenoms, and other medications.","specificNumbers":"Not specified — methodological scoping review.","methodology":"Scoping review of electrophysiological methods used in peptide toxin research, with focus on Central and South American research capacity.","limitations":"Scoping review focused on methodology rather than specific drug development outcomes. Primarily identifies gaps rather than solutions."},{"rthcId":"RPEP-09168","title":"An evolving machine-learning-based algorithm to early predict response to anti-CGRP monoclonal antibodies in patients with migraine.","authors":"Romozzi, Marina; Lokhandwala, Ammar; Vollono, Catello; Vigani, Giulia; Burgalassi, Andrea; García-Azorín, David; Calabresi, Paolo; Chiarugi, Alberto; Geppetti, Pierangelo; Iannone, Luigi Francesco","year":2024,"journal":"Cephalalgia : an international journal of headache, 44(12), 3331024241262751","doi":"10.1177/03331024241262751","pmid":"39654467","tags":["cgrp","migraine"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Machine learning models using early treatment data (up to one month) can predict 3-, 6-, and 12-month response to anti-CGRP antibodies in migraine patients.","whyItMatters":"CGRP antibodies are expensive and not every patient responds. Being able to predict who will benefit early could save time, money, and help patients get to effective treatment faster.","specificNumbers":"Models predicted responses at 3, 6, and 12 months using predictors available within the first month of treatment. Data included monthly headache days and acute medication use.","methodology":"Prospective cohort study collecting demographic and monthly clinical data from migraine patients receiving anti-CGRP mAbs for 12 months, with machine learning model development.","limitations":"The model needs external validation in other patient populations. Machine learning predictions are probabilistic, not certain, for individual patients."},{"rthcId":"RPEP-09169","title":"Predicting variable-length ACE inhibitory peptides based on graph convolutional network.","authors":"Rong, Yating; Feng, Baolong; Cai, Xiaoshuang; Song, Hongjie; Wang, Lili; Wang, Yehui; Yan, Xinxu; Sun, Yulin; Zhao, Jinyong; Li, Ping; Yang, Huihui; Wang, Yutang; Wang, Fengzhong","year":2024,"journal":"International journal of biological macromolecules, 282(Pt 5), 137060","doi":"10.1016/j.ijbiomac.2024.137060","pmid":"39481706","tags":["blood-pressure","peptide-engineering","bioactive-peptides"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"A graph convolutional network using molecular graph representations outperformed traditional machine learning models for predicting ACE-inhibitory peptides of varying lengths.","whyItMatters":"ACE inhibitors are among the most prescribed blood pressure drugs. Finding new ACE-inhibiting peptides from natural sources could provide alternative or complementary treatments.","specificNumbers":"Peptides containing 2-10 amino acids were represented as molecular graphs. The GCN model was compared against random forest, support vector machine, and other ML models.","methodology":"Computational study comparing graph convolutional network models to traditional ML models for predicting ACE-inhibitory activity of peptides with 2-10 amino acids.","limitations":"Computational predictions need experimental validation. The model's accuracy may vary for peptides outside the training data range."},{"rthcId":"RPEP-09170","title":"The adipose tissue melanocortin 3 receptor is targeted by ghrelin and leptin and may be a therapeutic target in obesity.","authors":"Rosendo-Silva, Daniela; Lopes, Eduardo; Monteiro-Alfredo, Tamaeh; Falcão-Pires, Inês; Eickhoff, Hans; Viana, Sofia; Reis, Flávio; Pires, Ana Salomé; Abrantes, Ana Margarida; Botelho, Maria Filomena; Seiça, Raquel; Matafome, Paulo","year":2024,"journal":"Molecular and cellular endocrinology, 594, 112367","doi":"10.1016/j.mce.2024.112367","pmid":"39293775","tags":["weight-loss","hormonal-peptides","receptor-signaling","diabetes"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"The melanocortin 3 receptor in adipose tissue is regulated by ghrelin and leptin, and its disruption in obesity suggests it could be a therapeutic target for metabolic disease.","whyItMatters":"Most obesity treatments target the brain. Finding that fat tissue has its own appetite-related signaling system opens an entirely new avenue for treatment.","specificNumbers":"Expression of NPY/melanocortin receptors was assessed in visceral adipose tissue of individuals with obesity and altered metabolism.","methodology":"Analysis of NPY/melanocortin receptor expression in visceral fat tissue from individuals with obesity and metabolic dysfunction, combined with mechanistic studies.","limitations":"Early-stage research characterizing receptor expression. Therapeutic targeting of MC3R in fat tissue has not been tested yet."},{"rthcId":"RPEP-09171","title":"Harmine and exendin-4 combination therapy safely expands human β cell mass in vivo in a mouse xenograft system.","authors":"Rosselot, Carolina; Li, Yansui; Wang, Peng; Alvarsson, Alexandra; Beliard, Kara; Lu, Geming; Kang, Randy; Li, Rosemary; Liu, Hongtao; Gillespie, Virginia; Tzavaras, Nikolaos; Kumar, Kunal; DeVita, Robert J; Stewart, Andrew F; Stanley, Sarah A; Garcia-Ocaña, Adolfo","year":2024,"journal":"Science translational medicine, 16(755), eadg3456","doi":"10.1126/scitranslmed.adg3456","pmid":"38985854","tags":["glp-1-receptor-agonists","diabetes","beta-cells"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"Harmine plus exendin-4 combination therapy safely increased human beta cell mass in vivo in a mouse xenograft system without causing harmful proliferation.","whyItMatters":"537 million people worldwide have diabetes, and beta cell loss is a core problem. A drug combination that safely expands beta cells could fundamentally change diabetes treatment.","specificNumbers":"537 million people globally have diabetes. No current diabetes drugs increase beta cell numbers. The combination used harmine (DYRK1A inhibitor) and exendin-4 (GLP-1R agonist).","methodology":"In vivo mouse xenograft study using transplanted human beta cells, testing harmine (DYRK1A inhibitor) combined with exendin-4 (GLP-1R agonist).","limitations":"This was done in mice with transplanted human cells, not in human patients. Safety and efficacy in humans remain to be demonstrated."},{"rthcId":"RPEP-09172","title":"Liraglutide prevents body and fat mass gain in ovariectomized Wistar rats.","authors":"Rossetti, Camila Lüdke; Andrade, Iris Soares; Fonte Boa, Luiz Fernando; Neves, Marcelo Barbosa; Fassarella, Larissa Brito; Bertasso, Iala Milene; Souza, Maria das Graças Coelho de; Bouskela, Eliete; Lisboa, Patrícia Cristina; Takyia, Christina Maeda; Trevenzoli, Isis Hara; Fortunato, Rodrigo Soares; Carvalho, Denise Pires de","year":2024,"journal":"Molecular and cellular endocrinology, 594, 112374","doi":"10.1016/j.mce.2024.112374","pmid":"39306226","tags":["liraglutide","glp-1-receptor-agonists","weight-loss","hormonal-peptides"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Liraglutide prevented body weight gain, fat mass accumulation, and glucose intolerance in ovariectomized rats, a model of post-menopausal metabolic changes.","whyItMatters":"Many women gain significant weight during menopause due to declining estrogen. GLP-1 drugs might offer a targeted treatment option for this specific type of weight gain.","specificNumbers":"Ovariectomy led to increased body weight, adipose tissue mass, basal blood glucose, and impaired glucose tolerance. Liraglutide prevented these effects.","methodology":"Animal study using Wistar rats — control group, ovariectomized group, and ovariectomized + liraglutide group.","limitations":"This is a rat study, and results may not directly translate to human menopause. Ovariectomy in young rats is not identical to natural menopause."},{"rthcId":"RPEP-09173","title":"GLP-1 receptor agonist improves metabolic disease in a pre-clinical model of lipodystrophy.","authors":"Roumane, Ahlima; Mcilroy, George D; Sommer, Nadine; Han, Weiping; Heisler, Lora K; Rochford, Justin J","year":2024,"journal":"Frontiers in endocrinology, 15, 1379228","doi":"10.3389/fendo.2024.1379228","pmid":"38745956","tags":["glp-1-receptor-agonists","diabetes","rare-diseases"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"A GLP-1 receptor agonist improved glucose intolerance, insulin resistance, and metabolic disease in lipodystrophic mice, even in the near-complete absence of adipose tissue.","whyItMatters":"People with lipodystrophy have very few treatment options. Showing that GLP-1 drugs work even without fat tissue expands their potential use to rare metabolic conditions.","specificNumbers":"Seipin knockout mice have generalized lipodystrophy with almost no fat tissue. This is the first detailed investigation of GLP-1R agonists in this condition.","methodology":"Preclinical study using seipin knockout mice (a model of congenital generalized lipodystrophy) treated with a GLP-1R agonist.","limitations":"Mouse model of lipodystrophy may not perfectly replicate human disease. Small sample sizes typical of rare disease research."},{"rthcId":"RPEP-09174","title":"Self-Assembling Peptides with Insulin-Like Growth Factor Mimicry.","authors":"Roy, Abhishek; Dodd-O, Joseph B; Robang, Alicia S; He, Dongjing; West, Owen; Siddiqui, Zain; Aguas, Erika Davidoff; Goldberg, Hannah; Griffith, Alexandra; Heffernan, Corey; Hu, Yuhang; Paravastu, Anant K; Kumar, Vivek A","year":2024,"journal":"ACS applied materials & interfaces, 16(1), 364-375","doi":"10.1021/acsami.3c15660","pmid":"38145951","tags":["self-assembling-peptides","growth-factors","peptide-engineering","tissue-engineering"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Self-assembling peptides were engineered to mimic IGF signaling and form biocompatible hydrogels that activate IGF receptors, providing localized growth factor signaling for tissue engineering.","whyItMatters":"Tissue engineering needs reliable ways to deliver growth signals. Building the signal directly into a self-assembling scaffold eliminates the need for separate growth factor delivery.","specificNumbers":"Not specified — proof-of-concept study demonstrating the peptide design and signaling capabilities.","methodology":"Laboratory development and testing of self-assembling peptide hydrogels with IGF-mimicking domains, including biocompatibility and receptor binding assays.","limitations":"In vitro study — needs in vivo validation. Long-term stability and signaling duration need assessment."},{"rthcId":"RPEP-09175","title":"Transforming Diabetes Care: The Molecular Pathways through Which GLP1-RAs Impact the Kidneys in Diabetic Kidney Disease.","authors":"Rroji, Merita; Spasovski, Goce","year":2024,"journal":"Biomedicines, 12(3)","doi":"10.3390/biomedicines12030657","pmid":"38540270","tags":["glp-1-receptor-agonists","kidney","diabetes"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"GLP-1 receptor agonists protect kidneys in diabetic kidney disease through anti-inflammatory, antioxidant, and anti-fibrotic molecular pathways, complementing existing kidney therapies.","whyItMatters":"Diabetic kidney disease is a leading cause of kidney failure worldwide. Understanding the molecular mechanisms of protection helps optimize treatment combinations.","specificNumbers":"GLP-1RAs enhance insulin release and reduce glucagon release. The review covers molecular pathways including inflammation, oxidative stress, and fibrosis.","methodology":"Comprehensive molecular pathways review examining preclinical and clinical evidence for GLP-1RA kidney protection in diabetic kidney disease.","limitations":"Much of the molecular pathway data comes from animal studies. Clinical evidence is growing but some mechanisms need further human validation."},{"rthcId":"RPEP-09176","title":"Could CGRP mAbs for migraine trigger rheumatoid arthritis? Insights from a case report.","authors":"Rua, Catarina; Beirão, Tiago; Silva, Catarina; Meirinhos, Tiago; Pinto, Patricia; Vieira, Romana; Aleixo-Santos, Joana; Costa, Flávio; Fonseca, Diogo; Pinto, Ana Sofia; Samões, Beatriz; Videira, Taciana","year":2024,"journal":"ARP rheumatology, 3(4), 337-338","doi":"10.63032/LZFI4171","pmid":"39754737","tags":["cgrp","migraine","peptide-safety","autoimmune"],"studyType":"case series","evidenceStrength":"preliminary","keyFinding":"A patient developed rheumatoid arthritis three months after starting CGRP antibody therapy for migraines, suggesting potential autoimmune triggering as an adverse effect.","whyItMatters":"CGRP antibodies are widely prescribed for migraine prevention. If they can trigger autoimmune conditions in susceptible individuals, this would be an important safety consideration.","specificNumbers":"56-year-old woman, fremanezumab 225 mg monthly, symptoms emerged at 3 months. Lab tests showed elevated inflammatory markers and positive anti-CCP antibodies.","methodology":"Single case report with clinical examination, laboratory tests, and autoimmune marker analysis.","limitations":"This is a single case report. Temporal association does not prove causation. The patient may have been developing RA independently."},{"rthcId":"RPEP-09177","title":"Scoping Review: The Effects of Interrupted Onabotulinumtoxin A Treatment for Chronic Migraine Prevention During the COVID-19 Pandemic.","authors":"Ruan, Qing Zhao; Pak, Daniel J; Gulati, Amitabh; Dominguez, Moises; Diwan, Sudhir; Hasoon, Jamal; Deer, Timothy R; Yong, R Jason; Albilali, Abdulrazaq; Macone, Amanda; Ashina, Sait; Robinson, Christopher L","year":2024,"journal":"Journal of pain research, 17, 4163-4176","doi":"10.2147/JPR.S485548","pmid":"39679430","tags":["botulinum-toxin","migraine"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Interruption of scheduled Botox injections during COVID-19 led to migraine worsening in most patients, emphasizing the importance of treatment continuity for chronic migraine.","whyItMatters":"This real-world natural experiment showed how dependent many chronic migraine patients are on regular Botox treatment, and highlighted the need for backup treatment plans.","specificNumbers":"Not specified — review of published studies documenting the impact of treatment delays.","methodology":"Scoping review of published literature on the effects of COVID-19 pandemic delays on Botox treatment for chronic migraine.","limitations":"Scoping review of observational reports, not controlled studies. The pandemic affected many aspects of health and well-being beyond migraine treatment."},{"rthcId":"RPEP-09178","title":"Efficacy and safety of semaglutide 2.4 mg by race and ethnicity: A post hoc analysis of three randomized controlled trials.","authors":"Rubino, Domenica; Angelene, Hanna; Fabricatore, Anthony; Ard, Jamy","year":2024,"journal":"Obesity (Silver Spring, Md.), 32(7), 1268-1280","doi":"10.1002/oby.24042","pmid":"38932728","tags":["semaglutide","weight-loss"],"studyType":"RCT","evidenceStrength":"strong","keyFinding":"Semaglutide 2.4 mg produced significant and consistent weight loss across racial and ethnic subgroups in the STEP trials, with comparable safety profiles.","whyItMatters":"Obesity disproportionately affects certain racial and ethnic groups. Confirming that semaglutide works across these populations helps ensure equitable treatment access and expectations.","specificNumbers":"STEP 1 and 3 data were pooled; STEP 2 analyzed separately. Primary outcome: percent body weight change from baseline. Semaglutide 2.4 mg given once weekly subcutaneously.","methodology":"Post hoc subgroup analysis of three phase 3 randomized controlled trials (STEP 1, 2, and 3) by race and ethnicity.","limitations":"Post hoc subgroup analysis has less statistical power than a study designed for this comparison. Some subgroups may have been small."},{"rthcId":"RPEP-09179","title":"Peptide receptor radionuclide therapy with 177Lu- or 90Y-SSTR peptides in malignant pheochromocytomas (PCCs) and paragangliomas (PGLs): results from a single institutional retrospective analysis.","authors":"Rubino, Manila; Di Stasio, Giuseppe Danilo; Bodei, Lisa; Papi, Stefano; Rocca, Paola Anna; Ferrari, Mahila Esmeralda; Fodor, Cristiana Iuliana; Bagnardi, Vincenzo; Frassoni, Samuele; Mei, Riccardo; Fazio, Nicola; Ceci, Francesco; Grana, Chiara Maria","year":2024,"journal":"Endocrine, 84(2), 704-710","doi":"10.1007/s12020-024-03707-5","pmid":"38324106","tags":["peptide-drug-conjugates","cancer","radionuclide-therapy"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Peptide receptor radionuclide therapy with 177Lu or 90Y peptides provided disease control in patients with malignant pheochromocytomas and paragangliomas.","whyItMatters":"These rare tumors have very limited treatment options, especially when they have spread. Any therapy showing disease control provides hope for patients with few alternatives.","specificNumbers":"30 patients identified from over 1,500 neuroendocrine tumor patients treated from 1999 to 2017. Treatment used 177Lu- or 90Y-DOTA-TATE or -TOC peptides.","methodology":"Single-center retrospective analysis of 30 patients with malignant PCCs/PGLs treated with PRRT between 1999 and 2017, selected from over 1,500 neuroendocrine tumor patients.","limitations":"Retrospective single-center study with only 30 patients. No control group for comparison. Patient selection may have influenced outcomes."},{"rthcId":"RPEP-09180","title":"Fenofibrate ameliorates nitroglycerin-induced migraine in rats: Role of CGRP/p-CREB/P2X3 and NGF/PKC/ASIC3 signaling pathways.","authors":"Ruby, Hassan A; Sayed, Rabab H; Khattab, Mohamed A; Sallam, Nada A; Kenway, Sanaa A","year":2024,"journal":"European journal of pharmacology, 976, 176667","doi":"10.1016/j.ejphar.2024.176667","pmid":"38795754","tags":["cgrp","migraine"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Fenofibrate reduced migraine symptoms in rats by lowering CGRP levels and modulating CGRP/p-CREB/P2X3 and NGF/PKC/ASIC3 signaling pathways.","whyItMatters":"Repurposing existing drugs for new conditions is faster and cheaper than developing new ones. If fenofibrate works for migraines, it could provide another affordable treatment option.","specificNumbers":"Migraine induced by 5 doses of nitroglycerin (10 mg/kg) on days 1, 3, 5, 7, and 9. Fenofibrate compared to topiramate (80 mg/kg/day oral).","methodology":"Animal study using nitroglycerin-induced chronic migraine model in rats, comparing fenofibrate to topiramate with molecular pathway analysis.","limitations":"Animal study — migraine in rats is modeled, not identical to human migraine. Doses used may not translate directly to human dosing."},{"rthcId":"RPEP-09181","title":"Glucagon-like Peptide-1 Receptor Agonists and Suicidal Ideation: Analysis of Real-Word Data Collected in the European Pharmacovigilance Database.","authors":"Ruggiero, Rosanna; Mascolo, Annamaria; Spezzaferri, Angela; Carpentieri, Claudia; Torella, Daniele; Sportiello, Liberata; Rossi, Francesco; Paolisso, Giuseppe; Capuano, Annalisa","year":2024,"journal":"Pharmaceuticals (Basel, Switzerland), 17(2)","doi":"10.3390/ph17020147","pmid":"38399362","tags":["glp-1-receptor-agonists","semaglutide","liraglutide","peptide-safety","mental-health"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Disproportionality analysis of the European Pharmacovigilance database found no elevated signal for suicidal events with GLP-1 receptor agonists as a class.","whyItMatters":"Millions of people take GLP-1 drugs, and a possible suicide link would be a major safety concern. This analysis helps put those concerns in perspective.","specificNumbers":"230 reports of suicidal events identified over 5.5 years (January 2018 to July 2023). Reporting odds ratios were calculated for the GLP-1 RA class.","methodology":"Retrospective pharmacovigilance study using disproportionality analysis (reporting odds ratios) of the European Pharmacovigilance database from January 2018 to July 2023.","limitations":"Spontaneous reporting databases have known limitations including underreporting, reporting bias, and inability to establish causation. The analysis can only assess reporting patterns, not true incidence."},{"rthcId":"RPEP-09182","title":"Unlocking the potential of luteolin: A natural migraine management approach through network pharmacology.","authors":"Rushendran, Rapuru; Vellapandian, Chitra","year":2024,"journal":"Journal of traditional and complementary medicine, 14(6), 611-621","doi":"10.1016/j.jtcme.2024.04.011","pmid":"39850605","tags":["cgrp","migraine","bioactive-peptides"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Computational analysis shows luteolin can bind to CGRP protein and multiple migraine-related molecular targets, suggesting it could be explored as a natural anti-migraine compound.","whyItMatters":"Natural compounds that can interact with migraine pathways could eventually provide complementary treatment options with potentially fewer side effects than prescription drugs.","specificNumbers":"Luteolin was analyzed for pharmacokinetic properties, toxicity, and binding affinity to CGRP and other migraine targets using multiple computational platforms.","methodology":"Network pharmacology approach combining pharmacokinetic assessment, toxicity analysis, and molecular docking simulations for luteolin against migraine targets.","limitations":"Entirely computational — no actual testing in cells, animals, or humans. Low water solubility and limited skin permeability are practical challenges identified."},{"rthcId":"RPEP-09183","title":"Regulatory T cells require peripheral CCL2-CCR2 signaling to facilitate the resolution of medication overuse headache-related behavioral sensitization.","authors":"Ryu, Sun; Zhang, Jintao; Simoes, Roli; Liu, Xuemei; Guo, Zhaohua; Feng, Li; Unsinger, Jacqueline; Hotchkiss, Richard S; Cao, Yu-Qing","year":2024,"journal":"The journal of headache and pain, 25(1), 197","doi":"10.1186/s10194-024-01900-5","pmid":"39528947","tags":["cgrp","migraine"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"CGRP, CCL2, and CCR2 knockout mice all developed normal sumatriptan-induced medication overuse headache, proving these pathways are not required for MOH development. This is surprising because CGRP is central to chronic migraine. However, low-dose IL-2 treatment — which reverses MOH by expanding regulatory T cells — requires intact CCL2-CCR2 signaling to traffic Treg cells to the dura and trigeminal ganglia. Repeated sumatriptan did not enhance CGRP or PACAP signaling in trigeminal neurons.","whyItMatters":"Anti-CGRP therapies have revolutionized migraine treatment, but this study shows medication overuse headache operates through completely different molecular pathways. This means anti-CGRP drugs may not help MOH patients, and separate treatment strategies are needed — like the low-dose IL-2 approach tested here.","specificNumbers":"Not specified — preclinical mechanistic study.","methodology":"Mouse study using global gene knockouts (CCL2 KO, CCR2 KO, CGRPα KO) and antibody neutralization. MOH was induced by 12 days of daily sumatriptan. Behavioral sensitization was measured via periorbital mechanical thresholds. Calcium imaging assessed CGRP/PACAP signaling in trigeminal neurons. Flow cytometry and immunohistochemistry tracked regulatory T cell expansion and trafficking.","limitations":"Mouse model — MOH in mice may not fully replicate human medication overuse headache. Global gene knockouts may have compensatory mechanisms. Only sumatriptan-induced MOH was tested; other overused medications may involve different pathways. Low-dose IL-2 therapy is not yet tested in human headache patients."},{"rthcId":"RPEP-09184","title":"Vasoactive intestinal peptide-expressing interneurons modulate the effect of behavioral state on cortical activity.","authors":"Sabri, Ehsan; Batista-Brito, Renata","year":2024,"journal":"Frontiers in cellular neuroscience, 18, 1465836","doi":"10.3389/fncel.2024.1465836","pmid":"39329085","tags":["vip","neuroprotection"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Inhibiting VIP interneurons reduced the correlation between behavioral state (measured by facial motion) and individual neuron spiking. During the quiet state specifically, VIP inhibition decreased synchronous neuron firing but increased delta-band power and phase-locking of spikes to delta oscillations. This shows VIP interneurons modulate how behavioral state influences cortical activity across multiple timescales.","whyItMatters":"VIP is one of the brain's key neuropeptides, and VIP-expressing neurons form a distinct class of cortical inhibitory interneurons. Understanding how these peptide-defined neurons control brain state switching is fundamental to understanding attention, arousal, and potentially disorders where state regulation fails, such as ADHD or sleep disorders.","specificNumbers":"Not specified — basic neuroscience study.","methodology":"Animal study in mice using optogenetic or chemogenetic inhibition of VIP interneurons in the cortex. Neural activity was recorded during different behavioral states, assessed via facial motion tracking. Analysis included spike correlations, delta-band power, and phase-locking between spikes and local field potential oscillations.","limitations":"Mouse study — results may not directly translate to human cortical circuits. Only cortical activity was measured; VIP interneurons in other brain regions were not assessed. The study relied on optogenetic/chemogenetic manipulation, which affects all VIP neurons rather than specific subtypes."},{"rthcId":"RPEP-09185","title":"Comparative Analysis of IMT-P8 and LDP12 Cell-Penetrating Peptides in Increasing Immunostimulatory Properties of HIV-1 Nef-MPER-V3 Antigen.","authors":"Sadat, Seyed Mehdi; Jahedian, Shekoufa; Sabaghzadeh, Sahar; Larijani, Mona Sadat; Bolhassani, Azam","year":2024,"journal":"Protein and peptide letters, 31(10), 818-826","doi":"10.2174/0109298665337811241010104557","pmid":"39558498","tags":["cell-penetrating-peptides","antimicrobial-peptides","peptide-delivery"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"IMT-P8 linked to the HIV Nef-MPER-V3 antigen produced significantly higher IgG antibody levels than LDP12-linked antigen. When combined with HP91 adjuvant, IMT-P8 generated the strongest humoral response. IMT-P8 also induced more robust IFN-gamma production and cytotoxic T cell activation compared to LDP12, indicating superiority as both a humoral and cellular immune activator.","whyItMatters":"Cell-penetrating peptides are a promising technology for delivering vaccine antigens directly into immune cells, potentially improving vaccine efficacy. Identifying which CPPs work best for immune stimulation helps advance peptide-based vaccine delivery platforms — relevant beyond just HIV vaccines.","specificNumbers":"Two CPPs (IMT-P8 and LDP12) and two adjuvants (HP91 and HSP27) tested in female BALB/c mice.","methodology":"Animal study in female BALB/c mice. Recombinant fusion proteins were generated linking the HIV Nef-MPER-V3 antigen to either IMT-P8 or LDP12 cell-penetrating peptides. Mice were immunized with different regimens using HP91 or HSP27 as adjuvants. Immune responses were measured via ELISA for antibodies, cytokines, and granzyme B, plus CTL proliferation assays.","limitations":"Mouse study only — immune responses in BALB/c mice may not predict human responses. Only female mice were used. No challenge study was performed, so it's unknown whether the immune responses would actually protect against HIV infection. Small-scale preclinical work."},{"rthcId":"RPEP-09186","title":"Serum Levels of Pro-Brain Natriuretic Peptide and the Diagnosis and Prognosis of Cardiac Syncope.","authors":"Sadrzadeh, Sayyed Majid; Shahri, Bahram; Kamandi, Mostafa; Adimolmasali, Maryam; Rezvani Kakhki, Behrang; Feiz Disfani, Hamideh","year":2024,"journal":"Bulletin of emergency and trauma, 12(3), 130-135","doi":"10.30476/beat.2024.103126.1520","pmid":"39391362","tags":["natriuretic-peptides","cardiovascular"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Pro-BNP demonstrated 94.73% sensitivity and 56.79% specificity for diagnosing cardiac syncope. Higher Pro-BNP levels correlated with age, longer hospitalization, and ECG abnormalities. As an independent marker, Pro-BNP showed acceptable diagnostic performance for identifying cardiac causes of syncope in the emergency department.","whyItMatters":"Quickly identifying whether fainting has a cardiac cause is critical in emergency medicine — cardiac syncope can signal life-threatening conditions. A simple blood test measuring the natriuretic peptide Pro-BNP could help ER doctors rapidly triage syncope patients, though its moderate specificity means additional testing is still needed.","specificNumbers":"Not specified in abstract — analytical cross-sectional design with initial evaluations including history, physical exam, ECG, and blood sugar.","methodology":"Analytical cross-sectional study of 100 patients presenting with syncope. Patients underwent standard evaluation including history, physical exam, ECG, blood sugar, and as needed, brain CT, echocardiography, and CTA. Pro-BNP levels were measured and correlated with final diagnosis of cardiac vs. non-cardiac syncope.","limitations":"Small sample of only 100 patients at a single center. Cross-sectional design limits causal conclusions. Low specificity (56.8%) means many non-cardiac patients would have elevated Pro-BNP, requiring additional testing. No comparison with other biomarkers or scoring systems for syncope evaluation."},{"rthcId":"RPEP-09187","title":"Niacin-Cholic Acid-Peptide Conjugate Act as a Potential Antibiotic Adjuvant to Mitigate Polymicrobial Infections Caused by Gram-Negative Pathogens.","authors":"Safwan, Sayed M; Mehta, Devashish; Arora, Amit; Khatol, Steffi; Singh, Mohit; Rana, Kajal; Gupta, Sonu K; Kumar, Yashwant; Verma, Vikas; Saini, Varsha; Bajaj, Avinash","year":2024,"journal":"ACS infectious diseases, 10(12), 4146-4155","doi":"10.1021/acsinfecdis.4c00404","pmid":"39564818","tags":["antimicrobial-peptides","peptide-drug-conjugates"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"The niacin-cholic acid-peptide conjugate (amphiphile 1) acts as a membrane disruptor for Gram-negative bacteria, creating entry points for erythromycin. The combination was bactericidal against Gram-negative pathogens, eliminated monomicrobial and polymicrobial biofilms, and showed antibacterial effectiveness in wound infection models. This approach repurposes an existing antibiotic for infections it normally cannot treat.","whyItMatters":"Antibiotic resistance, especially in Gram-negative bacteria, is a global health crisis. Rather than developing entirely new antibiotics, this approach uses a peptide conjugate to make existing antibiotics work against bacteria they couldn't previously kill — a faster and cheaper path to new treatments.","specificNumbers":"Not specified — proof-of-concept study with the peptide conjugate designated as compound 1.","methodology":"Peptide conjugate design and synthesis, followed by in vitro testing against Gram-negative bacteria. Assessed membrane disruption, bactericidal activity, and biofilm elimination. Tested in monomicrobial and polymicrobial wound infection models.","limitations":"Primarily in vitro and wound model data — no systemic in vivo pharmacokinetics or toxicity data. Unclear whether the conjugate would be stable and effective in human wound environments. Only tested with erythromycin; other antibiotic combinations not explored. Long-term resistance development not assessed."},{"rthcId":"RPEP-09188","title":"Expression Analysis of SSTR 1, 2 and 3 in Small-cell Lung Cancer Patients as Targets for Future Peptide Receptor Radionuclide Therapy.","authors":"Sagie, Nitzan; Romanov, Elizabeth; Kezerle, Yarden; Meirovitz, Amichay; Sheva, Kim","year":2024,"journal":"Anticancer research, 44(9), 3807-3812","doi":"10.21873/anticanres.17206","pmid":"39197921","tags":["somatostatin","cancer","radionuclide-therapy"],"studyType":"cohort","evidenceStrength":"preliminary","keyFinding":"SSTR1 was absent in all SCLC samples. SSTR2 was expressed in 29.4% and SSTR3 in 4.35% of cases. Co-expression of SSTR2 and SSTR3 occurred in 5.3% of patients. Female patients showed a trend toward higher expression, and older patients trended toward lower SSTR2 expression, but neither reached statistical significance. Disease stage did not correlate with receptor expression.","whyItMatters":"Somatostatin analogue therapy and peptide receptor radionuclide therapy (PRRT) require the tumor to express somatostatin receptors. This study shows that while not all SCLC patients are candidates, nearly a third express SSTR2 — making screening worthwhile for identifying patients who could benefit from peptide-targeted treatments.","specificNumbers":"SSTR subtypes 1, 2, and 3 were analyzed using immunohistochemistry on SCLC tissue samples.","methodology":"Tissue microarray analysis of 147 paraffin-embedded SCLC samples. Immunohistochemistry using anti-SSTR1, SSTR2, and SSTR3 antibodies, calibrated with healthy human pancreatic islets as positive controls. Slides scored by stain intensity and percentage of stained cells.","limitations":"Retrospective tissue analysis without clinical outcomes data — receptor expression doesn't guarantee therapeutic response. Sample size of 147 is moderate. No predictors of expression reached statistical significance. Only three SSTR subtypes were tested; SSTR4 and SSTR5 were not assessed."},{"rthcId":"RPEP-09189","title":"Glucagon-like peptide-1 receptor agonist semaglutide reduces atrial fibrillation incidence: A systematic review and meta-analysis.","authors":"Saglietto, Andrea; Falasconi, Giulio; Penela, Diego; Francia, Pietro; Sau, Arunashis; Ng, Fu Siong; Dusi, Veronica; Castagno, Davide; Gaita, Fiorenzo; Berruezo, Antonio; De Ferrari, Gaetano Maria; Anselmino, Matteo","year":2024,"journal":"European journal of clinical investigation, 54(12), e14292","doi":"10.1111/eci.14292","pmid":"39058274","tags":["semaglutide","cardiovascular","glp-1-receptor-agonists"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Semaglutide reduced incident atrial fibrillation by 42% (RR 0.58, 95% CI 0.40–0.85) with no heterogeneity across studies (I² = 0%). The benefit was consistent between oral semaglutide (RR 0.53) and subcutaneous semaglutide (RR 0.59), with no significant difference between routes (p = 0.83). Meta-regression showed no influence of diabetes proportion (p = 0.14) or BMI (p = 0.60) on the effect.","whyItMatters":"Atrial fibrillation is the most common heart rhythm disorder and a major cause of stroke. While GLP-1 drugs as a class show neutral arrhythmia effects, semaglutide specifically may reduce AF risk — adding another cardiovascular benefit beyond weight loss, blood sugar control, and heart failure reduction.","specificNumbers":"Meta-analysis of RCTs in diabetic and non-diabetic patients at high cardiovascular risk.","methodology":"Systematic review and meta-analysis of 10 randomized controlled trials. Included 12,651 patients (7,285 semaglutide, 5,366 placebo) with median follow-up of 68 months. Random-effects model used to pool relative risk. Subgroup analyses by route of administration and meta-regression for diabetes and BMI.","limitations":"Post-hoc analysis of AF events from trials not specifically designed to study atrial fibrillation. AF events were not uniformly adjudicated across all trials. The mechanism behind the AF reduction is unclear. Long median follow-up (68 months) but individual trial durations varied. Predominantly high-CV-risk populations — may not apply to lower-risk patients."},{"rthcId":"RPEP-09190","title":"Toxicity Studies of Cardiac-Targeting Peptide Reveal a Robust Safety Profile.","authors":"Sahagun, Daniella A; Lopuszynski, Jack B; Feldman, Kyle S; Pogodzinski, Nicholas; Zahid, Maliha","year":2024,"journal":"Pharmaceutics, 16(1)","doi":"10.3390/pharmaceutics16010073","pmid":"38258084","tags":["peptide-delivery","cardiovascular","peptide-engineering"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"CTP (sequence: APHLSSQYSRT) showed no decrease in human cardiomyocyte viability in vitro. Of 78 protein channels tested, only OPRM1 and COX2 showed any interaction, and neither was expressed in mouse heart tissue. In 60 mice followed for up to 14 days, CTP caused no changes in blood pressure, blood counts, liver function, kidney function, thyroid function, or cardiac size/function on MRI. The peptide appears safe as a cardiac delivery vector.","whyItMatters":"Delivering drugs specifically to the heart while avoiding other organs is a major unmet need in cardiology. CTP already delivers imaging agents, drugs, nanoparticles, and even miRNA to heart cells within minutes. Demonstrating safety clears a critical hurdle toward human clinical trials.","specificNumbers":"CTP is a 12-amino-acid peptide (APHLSSQYSRT). It reaches cardiomyocytes within 5 minutes of intravenous injection.","methodology":"Combined in vitro and in vivo toxicity assessment. Cell viability tested in human left ventricular myocyte cell line. Ion channel and GPCR profiling across 78 targets. In vivo: 60 CD1 mice (male/female) received CTP at 150 µg/kg, with cohorts euthanized at days 0, 1, 2, 7, and 14 for blood counts, metabolic profiling, and organ function tests. Blood pressure monitored acutely at 10 mg/kg dose. Cardiac MRI before and after injection.","limitations":"Only acute single-dose toxicity tested — chronic administration effects unknown. Mice were tested with CTP alone, not conjugated to any therapeutic cargo (which could change the safety profile). Only 14-day follow-up. No human pharmacokinetic or toxicity data. GLP (good laboratory practice) studies still needed before human trials."},{"rthcId":"RPEP-09191","title":"Cyclic Peptides KS-133 and KS-487 Multifunctionalized Nanoparticles Enable Efficient Brain Targeting for Treating Schizophrenia.","authors":"Sakamoto, Kotaro; Iwata, Seigo; Jin, Zihao; Chen, Lu; Miyaoka, Tatsunori; Yamada, Mei; Katahira, Kaiga; Yokoyama, Rei; Ono, Ami; Asano, Satoshi; Tanimoto, Kotaro; Ishimura, Rika; Nakagawa, Shinsaku; Hirokawa, Takatsugu; Ago, Yukio; Miyako, Eijiro","year":2024,"journal":"JACS Au, 4(8), 2811-2817","doi":"10.1021/jacsau.4c00311","pmid":"39211592","tags":["vip","peptide-delivery","neuroprotection","cell-penetrating-peptides"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"KS-487-displaying nanoparticles encapsulating KS-133 successfully crossed the blood-brain barrier via subcutaneous injection. Pharmacokinetic analysis confirmed time-dependent transport of KS-133 into the brain. When administered to schizophrenia model mice, the nanoparticles significantly improved cognitive dysfunction. This is the first demonstration of a multipeptide nanoparticle achieving therapeutic efficacy by inhibiting VIPR2 in the brain.","whyItMatters":"Getting drugs into the brain is one of medicine's biggest challenges. This study shows that peptide-functionalized nanoparticles can solve two problems at once: crossing the blood-brain barrier (using KS-487) and delivering a therapeutic peptide (KS-133) to block a schizophrenia-linked receptor. This dual-peptide approach could be applied to other brain diseases.","specificNumbers":"Two cyclic peptides: KS-133 (VIPR2 selective antagonist) and KS-487 (LRP1 cluster IV binder).","methodology":"Nanoparticle preparation with KS-133 encapsulated and KS-487 displayed on the surface. Click chemistry conjugation of KS-487 with ICG for brain imaging. Subcutaneous and intravenous administration in mice. Fluorescence imaging confirmed brain accumulation. Pharmacokinetic analysis of brain transport. Cognitive testing in schizophrenia mouse models.","limitations":"Mouse study only — blood-brain barrier permeability and drug efficacy may differ in humans. Schizophrenia mouse models have limited translational value. Long-term safety of repeated dosing unknown. Only cognitive dysfunction was assessed; other schizophrenia symptoms not tested."},{"rthcId":"RPEP-09192","title":"Efficacy and safety of glucagon-like peptide-1 receptor agonists on prediabetes: a systematic review and meta-analysis of randomized controlled trials.","authors":"Salamah, Hazem Mohamed; Marey, Ahmed; Abugdida, Mohamed; Abualkhair, Khaled Alsayed; Elshenawy, Salem; Elhassan, Wael Atif Fadl; Naguib, Mostafa Mahmoud; Malnev, Dmitrii; Durrani, Jamrose; Bailey, Ronelle; Tsyunchyk, Anastasiia; Ibrahim, Lena; Zavgorodneva, Zhanna; Sherazi, Andleeb","year":2024,"journal":"Diabetology & metabolic syndrome, 16(1), 129","doi":"10.1186/s13098-024-01371-3","pmid":"38877565","tags":["glp-1-receptor-agonists","diabetes","weight-loss"],"studyType":"meta-analysis","evidenceStrength":"moderate","keyFinding":"GLP-1RAs significantly increased prediabetes reversion to normoglycemia (RR 1.76, 95% CI 1.45–2.13, p < 0.00001) and prevented new-onset diabetes (RR 0.28, 95% CI 0.19–0.43, p < 0.00001). Significant reductions were also seen in HbA1c, fasting plasma glucose, body weight, waist circumference, triglycerides, and LDL cholesterol (all p < 0.05). Gastrointestinal disorders were more common with GLP-1RAs.","whyItMatters":"Prediabetes affects hundreds of millions worldwide and usually progresses to full diabetes over time. While lifestyle changes help, they're often insufficient. This meta-analysis provides the strongest evidence yet that GLP-1 drugs can actually reverse prediabetes — not just slow its progression — potentially preventing diabetes altogether.","specificNumbers":"GLP-1RAs were previously only evaluated as secondary and exploratory outcomes with limited sample sizes in prediabetes populations.","methodology":"Systematic review and meta-analysis of 12 randomized controlled trials identified from Web of Science, SCOPUS, PubMed, and Cochrane. Included 2,903 patients in GLP-1RA groups and 1,413 in control groups. Quality assessed using Cochrane Risk of Bias Tool. Evidence certainty evaluated using GRADE framework.","limitations":"Evidence for prediabetes reversion was rated low quality by GRADE. Diabetes prevention evidence was moderate quality. Studies had varying follow-up periods. GLP-1RA types and doses varied across trials. Higher gastrointestinal side effects may limit adherence. Cost-effectiveness not assessed."},{"rthcId":"RPEP-09193","title":"Rare cutaneous adverse reactions associated with GLP-1 agonists: a review of the published literature.","authors":"Salazar, Carlos E; Patil, Mihir K; Aihie, Osaigbokan; Cruz, Nicolas; Nambudiri, Vinod E","year":2024,"journal":"Archives of dermatological research, 316(6), 248","doi":"10.1007/s00403-024-02969-3","pmid":"38795152","tags":["glp-1-receptor-agonists","peptide-safety"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Reported cutaneous reactions to GLP-1 agonists include dermal hypersensitivity reactions, eosinophilic panniculitis, bullous pemphigoid, and morbilliform drug eruptions. These are rare but clinically significant. Diagnosis requires clinical suspicion, thorough medication history, and supporting histopathology when available. Management centers on stopping the GLP-1 drug and tailoring anti-inflammatory or immunomodulatory treatment to the specific reaction type.","whyItMatters":"Millions of people now take GLP-1 drugs. While skin reactions are rare, clinicians need to recognize them promptly since they can be mistaken for other dermatological conditions. As prescribing expands to weight loss populations, these reactions may become more frequently encountered.","specificNumbers":"GLP-1 agonists have demonstrated efficacy in reducing HbA1c, BMI, and cardiovascular events. Cutaneous reactions are rare but significant.","methodology":"Narrative review of published case reports and case series documenting cutaneous adverse reactions attributed to GLP-1 agonist use.","limitations":"Based entirely on case reports and case series — the lowest level of clinical evidence. No incidence rates can be calculated. Publication bias likely overrepresents unusual reactions. Cannot establish causation versus coincidence in individual cases."},{"rthcId":"RPEP-09194","title":"Nanostructured lipid carriers decorated with polyphosphate coated linear and loop cell-penetrating peptides.","authors":"Saleh, Ahmad; Stengel, Daniel; Truszkowska, Martyna; Blanco Massani, Mariana; Kali, Gergely; Bernkop-Schnürch, Andreas","year":2024,"journal":"International journal of pharmaceutics, 667(Pt A), 124844","doi":"10.1016/j.ijpharm.2024.124844","pmid":"39461677","tags":["cell-penetrating-peptides","peptide-delivery"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Polyphosphate coating shifted nanoparticle charge from positive to negative (masking CPP charge). Intestinal alkaline phosphatase cleaved the polyphosphate, causing charge conversion: from -22.2 mV to +5.3 mV for linear-CPP particles and from -19.2 mV to +11.9 mV for loop-CPP particles. Linear-CPP nanoparticles showed higher uptake on Caco-2 intestinal cells than loop-CPP variants. Enzyme inhibition confirmed alkaline phosphatase drives the charge conversion.","whyItMatters":"The 'polycationic dilemma' — CPPs need a positive charge to enter cells but that charge causes hemolysis and toxicity — has been a major barrier to clinical CPP use. This enzyme-triggered charge-switching approach elegantly solves the problem, potentially enabling safer oral peptide drug delivery.","specificNumbers":"Nanocarriers characterized for particle size, polydispersity index, and zeta potential. Both linear-CPP and loop-CPP variants tested.","methodology":"In vitro study. Linear and loop CPPs were synthesized and attached to nanostructured lipid carriers (NLCs), then coated with polyphosphate. Characterized for size (<270 nm), polydispersity, and zeta potential. Cell viability and hemolysis assessed. Cellular uptake measured by flow cytometry and visualized with confocal microscopy in Caco-2 and HEK cells.","limitations":"In vitro only — no in vivo testing of oral delivery or biodistribution. Only two cell lines tested. Hemolysis at ~10% at working concentration may still be a concern. No therapeutic cargo was delivered — purely a delivery platform study. Stability in real GI conditions not tested."},{"rthcId":"RPEP-09195","title":"Synergism of Anti-CGRP Monoclonal Antibodies and OnabotulinumtoxinA in the Treatment of Chronic Migraine: A Real-World Retrospective Chart Review.","authors":"Salim, Amira; Hennessy, Elise; Sonneborn, Claire; Hogue, Olivia; Biswas, Sudipa; Mays, MaryAnn; Suneja, Aarushi; Ahmed, Zubair; Mata, Ignacio F","year":2024,"journal":"CNS drugs, 38(6), 481-491","doi":"10.1007/s40263-024-01086-z","pmid":"38583127","tags":["cgrp","botulinum-toxin","migraine"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Dual therapy reduced median monthly migraine days from 30 to 15 after the first treatment, then further to 8 after adding the second (p < 0.0001 for both reductions). Among 194 dual-therapy patients, 68% achieved ≥50% reduction and 46.4% achieved ≥75% reduction in monthly migraine days. Consecutive monotherapy reduced migraine days less effectively: onabot alone to 15, anti-CGRP alone to 12. Only 16.6-19.7% of monotherapy patients achieved ≥75% reduction. Dual therapy was significantly better than either monotherapy (p < 0.0001).","whyItMatters":"Most chronic migraine patients don't get adequate relief from a single treatment. Anti-CGRP antibodies and Botox target different aspects of migraine biology — CGRP blocks the pain signal peptide, while Botox reduces peripheral sensitization. This study provides real-world evidence that combining them works better than either alone, from median 30 to 8 migraine days per month.","specificNumbers":"Median monthly migraine days measured during monotherapy periods versus combination therapy periods.","methodology":"Retrospective cohort study using Cleveland Clinic electronic medical records from June 2018 to November 2021. Compared 194 concurrent dual-therapy patients with 229 consecutive monotherapy patients. Monthly migraine days tracked at baseline, after first therapy, and after 3 months of dual therapy.","limitations":"Retrospective study without randomization — patients who received dual therapy may differ from monotherapy patients. No blinding or placebo control. Cleveland Clinic population may not represent all migraine patients. Self-reported migraine days subject to recall bias. Insurance and access factors may have influenced who received dual therapy."},{"rthcId":"RPEP-09196","title":"Evaluating the Impact of Novel Incretin Therapies on Cardiovascular Outcomes in Type 2 Diabetes: An Early Systematic Review.","authors":"Salmen, Teodor; Potcovaru, Claudia-Gabriela; Bica, Ioana-Cristina; Giglio, Rosaria Vincenza; Patti, Angelo Maria; Stoica, Roxana-Adriana; Ciaccio, Marcello; El-Tanani, Mohamed; Janež, Andrej; Rizzo, Manfredi; Gherghiceanu, Florentina; Stoian, Anca Pantea","year":2024,"journal":"Pharmaceuticals (Basel, Switzerland), 17(10)","doi":"10.3390/ph17101322","pmid":"39458963","tags":["tirzepatide","glp-1-receptor-agonists","cardiovascular","diabetes"],"studyType":"meta-analysis","evidenceStrength":"moderate","keyFinding":"Both tirzepatide and retatrutide improve glycemia, HbA1c, body weight, lipid profiles, blood pressure, and renal parameters in type 2 diabetes patients. Tirzepatide has recent proven cardiovascular benefits from dedicated outcomes trials. Retatrutide data is more limited, coming from earlier-phase trials. Both drugs show promising CV risk marker improvement, but standardized long-term follow-up is needed, especially for retatrutide.","whyItMatters":"The incretin therapy landscape is evolving rapidly from single GLP-1 agonists to dual (tirzepatide) and triple (retatrutide) receptor agonists. Understanding how these multi-target drugs compare for cardiovascular protection helps clinicians and patients make informed treatment choices as more options become available.","specificNumbers":"Review covered original RCTs from the last 10 years in adult human populations. Compared known data for retatrutide vs. tirzepatide.","methodology":"Systematic review registered with PROSPERO (CRD42024507397). Included original RCTs from the last 10 years in English, conducted in adult human populations. Excluded cell/animal studies, case reports, reviews, and incomplete data. Seven studies assessed for bias using the Newcastle-Ottawa scale.","limitations":"Only seven studies met inclusion criteria — limited evidence base especially for retatrutide. Heterogeneous study designs and follow-up periods. No direct head-to-head trials comparing tirzepatide to retatrutide. Long-term CV outcomes data not yet available for retatrutide. Assessment limited to metabolic surrogate markers rather than hard CV endpoints for retatrutide."},{"rthcId":"RPEP-09197","title":"Dual effects of dulaglutide on glycemic control and knee osteoarthritis pain in elderly patients with Type 2 diabetes.","authors":"Samajdar, Shambo Samrat; Bhaduri, Gaurab; Ghoshal, Pradip Kumar; Mukherjee, Shatavisa; Pal, Jyotirmoy; Chatterjee, Nandini; Joshi, Shashank R","year":2024,"journal":"Pain management, 14(7), 365-373","doi":"10.1080/17581869.2024.2402214","pmid":"39301951","tags":["glp-1-receptor-agonists","diabetes","inflammation"],"studyType":"cohort","evidenceStrength":"preliminary","keyFinding":"HbA1c decreased from 8.7% to 6.5% over 6 months. Pain scores, NSAID consumption, body weight, and BMI all showed substantial reductions. A strong positive correlation (r = 0.73, p < 0.05) was found between glycemic improvement and pain reduction, suggesting the benefits may be mechanistically linked through GLP-1's anti-inflammatory properties.","whyItMatters":"Many elderly patients have both diabetes and osteoarthritis, requiring multiple medications. If a single drug can improve both conditions simultaneously, it simplifies treatment and reduces polypharmacy. The anti-inflammatory properties of GLP-1 drugs may explain the joint pain benefit.","specificNumbers":"HbA1c decreased from 8.7% to 6.5% over 6 months. Pain scores and NSAID consumption measured at baseline, 3, and 6 months.","methodology":"Prospective cohort study of elderly type 2 diabetes patients with bilateral knee osteoarthritis on conventional OA treatment for at least 3 months. Glycemic metrics, OA pain scores, and NSAID consumption measured at baseline, 3 months, and 6 months after starting dulaglutide.","limitations":"Observational cohort without a control group or randomization. Cannot establish causation — pain reduction could be from weight loss rather than direct anti-inflammatory effects. Sample size not specified. No imaging to confirm structural joint changes. Short 6-month follow-up."},{"rthcId":"RPEP-09198","title":"Adverse event comparison between glucagon-like peptide-1 receptor agonists and other antiobesity medications following bariatric surgery.","authors":"Samuels, Jason M; Niswender, Kevin D; Roumie, Christianne L; Spann, Matthew D; Flynn, C Robb; Ye, Fei; Blankush, Joseph; Irlmeier, Rebecca; Funk, Luke M; Patel, Mayur B","year":2024,"journal":"Diabetes, obesity & metabolism, 26(9), 3906-3913","doi":"10.1111/dom.15737","pmid":"38934217","tags":["glp-1-receptor-agonists","weight-loss","peptide-safety"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"GLP-1RA use was not associated with higher odds of adverse events compared to FDA-approved non-GLP-1 medications (aOR 1.1, 95% CI 0.5–2.6) or off-label medications (aOR 1.1, 95% CI 0.6–2.3). Notably, starting any antiobesity medication 12 or more months after surgery was associated with dramatically lower risk of adverse events compared to earlier initiation (aOR 0.01, 95% CI 0.0–0.01, p < 0.001).","whyItMatters":"Many bariatric surgery patients regain weight and need additional medications. Concerns about GLP-1 drug safety in this population — including delayed gastric emptying in an already altered GI anatomy — have limited prescribing. This study provides reassurance that GLP-1 drugs are as safe as alternatives in these patients.","specificNumbers":"Patients had laparoscopic Roux-en-Y gastric bypass or sleeve gastrectomy. Compared FDA-approved, off-label, and GLP-1RA antiobesity medications.","methodology":"Single-center retrospective cohort study of 599 patients aged 16-65 who underwent gastric bypass or sleeve gastrectomy and later initiated antiobesity medications. Patients categorized by medication type (GLP-1RA vs. non-GLP-1RA). Primary outcome: adverse event incidence. Univariate and multivariate logistic regression for risk factors.","limitations":"Single-center retrospective design with potential selection bias. Only 123 GLP-1 users — may be underpowered for rare events. No specific adverse event breakdown by type. Unable to determine causation. Timing finding (≥12 months safer) may reflect recovery rather than medication timing specifically."},{"rthcId":"RPEP-09199","title":"Immunohistochemistry Study of Antimicrobial Peptides as a Future Diagnostic and Prognostic Tool for Periprosthetic Joint Infections.","authors":"Sandu, Emanuel-Cristian; Serban, Bogdan; Iordache, Sergiu; Cursaru, Adrian; Costache, Mihai Aurel; Dumitru, Adrian; Cirstoiu, Catalin","year":2024,"journal":"Cureus, 16(9), e69629","doi":"10.7759/cureus.69629","pmid":"39429325","tags":["antimicrobial-peptides"],"studyType":"cohort","evidenceStrength":"preliminary","keyFinding":"Immunohistochemistry revealed significantly increased HBD-3 and LL-37 antimicrobial peptide levels in periprosthetic tissue from infected joint replacements versus aseptically loosened joints. Positive LL-37 staining was associated with a more reserved prognosis at one-year follow-up. Both peptides could serve as biomarkers for distinguishing septic from aseptic implant failure.","whyItMatters":"Misdiagnosing joint replacement infections leads to wrong treatment and poor outcomes. Current diagnostic methods are imperfect. Antimicrobial peptides measured directly in tissue could provide a faster, cheaper, and more accurate diagnostic tool — and LL-37 levels may also predict how well patients will do after treatment.","specificNumbers":"Not specified in abstract.","methodology":"Cohort study of 52 arthroplasty revision surgeries (septic and aseptic). Periprosthetic tissue analyzed by immunohistochemistry using anti-HBD-3 and anti-LL-37 antibodies. Staining intensity and percentage scored. One-year clinical outcomes compared between groups.","limitations":"Small sample of 52 surgeries — needs larger validation. Immunohistochemistry requires tissue biopsy, limiting use as a pre-operative screening tool. Retrospective design. No comparison with existing diagnostic methods (CRP, ESR, synovial fluid analysis). Only one-year follow-up."},{"rthcId":"RPEP-09200","title":"Class B1 GPCRs: insights into multireceptor pharmacology for the treatment of metabolic disease.","authors":"Sangwung, Panjamaporn; Ho, Joseph D; Siddall, Tessa; Lin, Jerry; Tomas, Alejandra; Jones, Ben; Sloop, Kyle W","year":2024,"journal":"American journal of physiology. Endocrinology and metabolism, 327(5), E600-E615","doi":"10.1152/ajpendo.00371.2023","pmid":"38984948","tags":["glp-1-receptor-agonists","receptor-signaling","tirzepatide"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Class B1 GPCRs use an evolutionarily conserved two-step activation mechanism: the C-terminus of the peptide ligand binds to an extracellular hydrophobic groove, then the N-terminus engages a large transmembrane pocket. This mechanism is shared across GLP-1, GIP, and glucagon receptors, which has enabled engineering of multifunctional agonists (like tirzepatide for GLP-1/GIP and emerging triple agonists for GLP-1/GIP/glucagon). Cryo-EM structures reveal how these polypharmacologic ligands interact with multiple receptors simultaneously.","whyItMatters":"Understanding exactly how peptide hormones activate their receptors at the structural level is what makes it possible to design multi-agonist drugs. This knowledge underpins the entire new generation of obesity and diabetes treatments — from semaglutide (single GLP-1 target) to tirzepatide (dual GLP-1/GIP) to retatrutide (triple GLP-1/GIP/glucagon).","specificNumbers":"15 members in the class B1 GPCR subfamily. Includes receptors for GLP-1, GIP, glucagon, and other metabolic hormones.","methodology":"Comprehensive review combining receptor pharmacology, signal transduction analysis, receptor trafficking studies, and comparative structural biology using high-resolution cryo-EM structures of receptors in complex with native ligands and engineered multifunctional agonists.","limitations":"Review article — no new experimental data. Structural analysis from cryo-EM provides snapshots but may not capture the full dynamics of receptor activation. The field is evolving rapidly, and newer multi-agonists may have features not covered here."},{"rthcId":"RPEP-09201","title":"Peptide Receptor Radionuclide Therapy of Neuroendocrine Tumors: Agonist, Antagonist and Alternatives.","authors":"Santo, Giulia; Di Santo, Gianpaolo; Virgolini, Irene","year":2024,"journal":"Seminars in nuclear medicine, 54(4), 557-569","doi":"10.1053/j.semnuclmed.2024.02.002","pmid":"38490913","tags":["somatostatin","cancer","radionuclide-therapy"],"studyType":"review","evidenceStrength":"strong","keyFinding":"PRRT is now incorporated into major oncology guidelines based on NETTER-1 trial results. The NETTER-2 trial may expand first-line use to G2/G3 NET patients. Dual tracer PET/CT using both FDG and Ga-68 DOTA-SSA could improve patient selection and prognostication. Combination therapies with other agents may enhance efficacy. Somatostatin receptor antagonists and alternative isotopes are being explored as next-generation options.","whyItMatters":"PRRT is the quintessential example of peptide-targeted therapy — using the body's own receptor system to guide radiation directly to tumor cells. Its success has validated the concept of 'theranostics' (using the same peptide for both imaging and therapy) and opened doors for similar approaches in other cancers.","specificNumbers":"PRRT was first performed over 30 years ago. Lutathera was FDA-approved in 2017 based on the NETTER-1 trial for G1/G2 NET patients.","methodology":"Comprehensive narrative review of clinical trials, treatment strategies, and emerging approaches in PRRT for neuroendocrine tumors.","limitations":"Narrative review without systematic methodology. Some emerging strategies discussed are still in early clinical development. Not all NET patients have sufficient somatostatin receptor expression for PRRT. Long-term side effects of repeated PRRT cycles need more study."},{"rthcId":"RPEP-09202","title":"Models using comprehensive, lesion-level, longitudinal [68Ga]Ga-DOTA-TATE PET-derived features lead to superior outcome prediction in neuroendocrine tumor patients treated with [177Lu]Lu-DOTA-TATE.","authors":"Santoro-Fernandes, Victor; Schott, Brayden; Deatsch, Ali; Keigley, Quinton; Francken, Thomas; Iyer, Renuka; Fountzilas, Christos; Perlman, Scott; Jeraj, Robert","year":2024,"journal":"European journal of nuclear medicine and molecular imaging, 51(11), 3428-3439","doi":"10.1007/s00259-024-06767-x","pmid":"38795121","tags":["somatostatin","cancer","radionuclide-therapy"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"A multivariate linear regression model using comprehensive, lesion-level, longitudinal features from Ga-68 DOTA-TATE PET scans achieved a concordance index of 0.826, AUC of 0.88 (85% specificity, 81% sensitivity), and significant patient stratification into good and poor responders (PFS ≥25 months cutoff, p < 0.00001). This approach outperformed all single-feature predictors in a benchmark study.","whyItMatters":"PRRT is expensive and not all patients respond equally. Being able to predict who will benefit — with 88% accuracy — could prevent unnecessary treatment for likely non-responders and fast-track therapy for likely responders. It also demonstrates the power of comprehensive peptide-receptor imaging analysis.","specificNumbers":"Models used comprehensive (all lesions), longitudinal (temporal), and lesion-level imaging features from 68Ga-DOTA-TATE PET scans.","methodology":"Retrospective study of 36 NET patients treated with 177Lu-DOTA-TATE and imaged with 68Ga-DOTA-TATE PET at baseline and post-therapy. All individual lesions were segmented, anatomically labeled, and longitudinally matched between scans. Patient-level features were engineered from lesion-level data and selected for multivariate modeling. Validated via concordance index, ROC analysis, and Kaplan-Meier survival analysis.","limitations":"Small cohort of only 36 patients — needs external validation in larger populations. Retrospective design. Comprehensive lesion segmentation is labor-intensive and not yet automated. Model performance may not generalize across different institutions or scanner types."},{"rthcId":"RPEP-09203","title":"Effect of various perioperative semaglutide interruption intervals on residual gastric content assessed by esophagogastroduodenoscopy: A retrospective single center observational study.","authors":"Santos, Leonardo Barbosa; Mizubuti, Glenio B; da Silva, Leopoldo Muniz; Silveira, Saullo Queiroz; Nersessian, Rafael Souza Fava; Abib, Arthur de Campos Vieira; Bellicieri, Fernando Nardy; Lima, Helidea de Oliveira; Ho, Anthony M-H; Dos Anjos, Gabriel Silva; de Moura, Diogo Turiani Hourneaux; de Moura, Eduardo Guimarães Hourneuax; Vieira, Joaquim Edson","year":2024,"journal":"Journal of clinical anesthesia, 99, 111668","doi":"10.1016/j.jclinane.2024.111668","pmid":"39476514","tags":["semaglutide","peptide-safety"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Semaglutide users had significantly higher rates of increased residual gastric content (20.3% vs 3.2%, p<0.001). Discontinuation >21 days in patients with digestive symptoms and >14 days in those without symptoms resulted in RGC comparable to non-users (OR 0.77, 95% CI 0.22-2.01).","whyItMatters":"Semaglutide and other GLP-1 receptor agonist peptides slow gastric emptying, which can leave food in the stomach during procedures requiring sedation — raising the risk of aspiration into the lungs. This study provides concrete timelines for when to stop the drug before surgery.","specificNumbers":"Various perioperative semaglutide interruption intervals compared. Residual gastric content assessed by esophagogastroduodenoscopy.","methodology":"Single-center retrospective chart review at a tertiary hospital. 1,094 patients undergoing esophagogastroduodenoscopy under deep sedation or general anesthesia (July 2021-July 2023) were divided into semaglutide (n=123) and non-semaglutide (n=971) groups. Increased RGC defined as any solid content or >0.8 mL/kg fluid. Univariate and multivariate logistic regression analyzed factors associated with increased RGC.","limitations":"Retrospective single-center design limits generalizability. RGC measurement from suction canisters is imprecise compared to gastric ultrasound. Semaglutide group was relatively small (n=123). Different semaglutide doses and formulations were not separately analyzed. Results may not apply to other GLP-1 agonists with different half-lives."},{"rthcId":"RPEP-09204","title":"Discovery of antimicrobial peptides in the global microbiome with machine learning.","authors":"Santos-Júnior, Célio Dias; Torres, Marcelo D T; Duan, Yiqian; Rodríguez Del Río, Álvaro; Schmidt, Thomas S B; Chong, Hui; Fullam, Anthony; Kuhn, Michael; Zhu, Chengkai; Houseman, Amy; Somborski, Jelena; Vines, Anna; Zhao, Xing-Ming; Bork, Peer; Huerta-Cepas, Jaime; de la Fuente-Nunez, Cesar; Coelho, Luis Pedro","year":2024,"journal":"Cell, 187(14), 3761-3778.e16","doi":"10.1016/j.cell.2024.05.013","pmid":"38843834","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09205","title":"A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis.","authors":"Sanyal, Arun J; Bedossa, Pierre; Fraessdorf, Mandy; Neff, Guy W; Lawitz, Eric; Bugianesi, Elisabetta; Anstee, Quentin M; Hussain, Samina Ajaz; Newsome, Philip N; Ratziu, Vlad; Hosseini-Tabatabaei, Azadeh; Schattenberg, Jörn M; Noureddin, Mazen; Alkhouri, Naim; Younes, Ramy","year":2024,"journal":"The New England journal of medicine, 391(4), 311-319","doi":"10.1056/NEJMoa2401755","pmid":"38847460","tags":["glp-1-receptor-agonists","liver"],"studyType":"RCT","evidenceStrength":"strong","keyFinding":"Survodutide achieved MASH improvement without fibrosis worsening in 47% (2.4 mg), 62% (4.8 mg), and 43% (6.0 mg) of participants vs 14% on placebo (P<0.001). Liver fat reduction ≥30% occurred in 57-67% of survodutide groups vs 14% placebo. Fibrosis improved by ≥1 stage in 34-36% vs 22% placebo.","whyItMatters":"MASH affects millions worldwide and has limited treatment options. Dual receptor agonism combining glucagon's fat-burning effects with GLP-1's metabolic benefits may offer a more powerful approach than GLP-1 alone, potentially changing how we treat this progressive liver disease.","specificNumbers":"48-week trial. Adults with biopsy-confirmed MASH and fibrosis stage F1-F3. Randomized 1:1:1:1 to different doses vs. placebo.","methodology":"Phase 2, randomized, double-blind, placebo-controlled trial. 293 adults with biopsy-confirmed MASH and fibrosis (F1-F3) randomized 1:1:1:1 to survodutide 2.4 mg, 4.8 mg, 6.0 mg, or placebo via weekly subcutaneous injection for 48 weeks (24-week dose escalation + 24-week maintenance). Primary endpoint: histologic MASH improvement without fibrosis worsening.","limitations":"Phase 2 trial — still needs phase 3 confirmation with larger numbers. The 6.0 mg dose unexpectedly performed worse than 4.8 mg, possibly due to tolerability-driven dropouts. High rates of GI side effects (nausea 66%, diarrhea 49%, vomiting 41%). 48-week duration may not capture long-term safety or sustained benefit."},{"rthcId":"RPEP-09206","title":"Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial.","authors":"Sanyal, Arun J; Kaplan, Lee M; Frias, Juan P; Brouwers, Bram; Wu, Qiwei; Thomas, Melissa K; Harris, Charles; Schloot, Nanette C; Du, Yu; Mather, Kieren J; Haupt, Axel; Hartman, Mark L","year":2024,"journal":"Nature medicine, 30(7), 2037-2048","doi":"10.1038/s41591-024-03018-2","pmid":"38858523","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09207","title":"Enzymatic Hydrolysis Systems Enhance the Efficiency and Biological Properties of Hydrolysates from Frozen Fish Processing Co-Products.","authors":"Sapatinha, Maria; Camacho, Carolina; Pais-Costa, Antónia Juliana; Fernando, Ana Luísa; Marques, António; Pires, Carla","year":2024,"journal":"Marine drugs, 23(1)","doi":"10.3390/md23010014","pmid":"39852515","tags":["bioactive-peptides","collagen-peptides"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Single-stage combined enzymatic hydrolysis (Alcalase + Protana) achieved 80% protein yield and 34-49% degree of hydrolysis, producing low-molecular-weight peptides. Hydrolysates showed ABTS antioxidant activity with EC50 below 5 mg/mL and over 60% ACE inhibition at 5 mg/mL. Gilthead seabream co-products yielded the most promising bioactive peptides.","whyItMatters":"Millions of tons of fish processing waste are discarded annually. Converting this waste into bioactive peptides with health-promoting properties — particularly blood pressure management — creates value from what was previously a financial loss while addressing sustainability challenges.","specificNumbers":"3 fish species' co-products tested with 4 enzymatic systems: Alcalase and others. Products included heads/bones, carcasses, and trimmings.","methodology":"Laboratory study testing four enzymatic hydrolysis systems (endopeptidase alone, exopeptidase alone, sequential two-stage, and combined single-stage) on co-products from three fish species. Hydrolysates evaluated for protein yield, degree of hydrolysis, molecular weight distribution, antioxidant activity (ABTS assay), ACE inhibition, and antidiabetic/anti-Alzheimer properties.","limitations":"In vitro study only — ACE inhibition in a test tube doesn't guarantee blood pressure reduction in humans. Bioavailability and stability of these peptides through digestion not tested. No dose-response or toxicity studies. Antidiabetic and anti-Alzheimer activities were low and likely not clinically meaningful."},{"rthcId":"RPEP-09208","title":"Engraulisin: A novel marine derived cell penetrating peptide with activity against drug resistant bacteria.","authors":"Saraswat, Saurabh; Chugh, Archana","year":2024,"journal":"Biochimica et biophysica acta. Biomembranes, 1866(2), 184255","doi":"10.1016/j.bbamem.2023.184255","pmid":"37995845","tags":["antimicrobial-peptides","cell-penetrating-peptides"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Engraulisin demonstrated successful cellular uptake in mammalian cells at 5 μM with negligible cytotoxicity (MTT assay). It entered cells primarily via endocytosis. The peptide showed selective antimicrobial activity against MRSA. Molecular dynamics simulations revealed positively charged residues form stable interactions with bacterial membrane models (POPC and POPG bilayers).","whyItMatters":"Antimicrobial resistance is a global health crisis, with MRSA infections causing tens of thousands of deaths annually. Cell-penetrating peptides that can also kill resistant bacteria represent a dual-function therapeutic platform — they could both deliver drugs inside cells and directly combat infections.","specificNumbers":"Not specified in abstract — characterization and activity study.","methodology":"Computational peptide design from Engraulis japonicus protein sequences, followed by in vitro validation. Cell uptake confirmed via fluorescence microscopy in mammalian cells. Cytotoxicity assessed by MTT assay. Uptake mechanism probed by temperature inhibition (4°C). Antimicrobial activity tested against drug-resistant bacteria. Molecular dynamics simulations with POPC and POPG membrane bilayers analyzed peptide-membrane interactions.","limitations":"In vitro study only — no animal or human testing. Antimicrobial activity shown only against MRSA; spectrum against other pathogens unclear. No minimum inhibitory concentration (MIC) values reported in the abstract. Stability, bioavailability, and in vivo efficacy unknown. Computationally designed — real-world therapeutic development requires extensive further validation."},{"rthcId":"RPEP-09209","title":"PIONEER REAL UK: A Multi-Centre, Prospective, Real-World Study of Once-Daily Oral Semaglutide Use in Adults with Type 2 Diabetes.","authors":"Saravanan, Ponnusamy; Bell, Heather; Braae, Uffe Christian; Collins, Edward; Deinega, Alisa; Dhatariya, Ketan; Machell, Alena; Trent, Antonia; Strzelecka, Anna","year":2024,"journal":"Advances in therapy, 41(11), 4266-4281","doi":"10.1007/s12325-024-02973-z","pmid":"39316289","tags":["semaglutide","diabetes","weight-loss"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Oral semaglutide reduced HbA1c by 1.1 percentage points (95% CI -1.27 to -0.96, P<0.001) and body weight by 4.4 kg in real-world UK clinical practice. 36.4% achieved combined HbA1c reduction plus ≥3% weight loss; 27.1% achieved HbA1c reduction plus ≥5% weight loss. No severe hypoglycemia or new safety signals.","whyItMatters":"Clinical trials show what a drug can do under ideal conditions. Real-world studies show what it actually does in everyday practice. This study confirms that oral semaglutide delivers meaningful blood sugar and weight benefits outside of tightly controlled trial settings, which is more relevant to typical patients.","specificNumbers":"333 participants enrolled. Follow-up: 34-44 weeks. Treated as part of routine clinical care.","methodology":"Multi-centre, prospective, non-interventional single-arm study (PIONEER REAL UK). 333 adults with T2D enrolled across UK sites and followed for 34-44 weeks. All treated with oral semaglutide as part of routine clinical practice. No prior injectable glucose-lowering medication. Primary endpoint: HbA1c change. Secondary: body weight change, proportion meeting combined targets, treatment satisfaction (DTSQ).","limitations":"Single-arm study with no control group — observed changes could partly reflect regression to the mean or concurrent lifestyle changes. 227 of 333 participants remained on treatment at end of study (32% dropout). Selection bias possible as physicians chose patients they deemed suitable. UK-specific results may not generalize to all healthcare systems."},{"rthcId":"RPEP-09210","title":"Mechanism of Protease Resistance of D-Amino Acid Residue Containing Cationic Antimicrobial Heptapeptides.","authors":"Sarkar, Tanumoy; Ghosh, Suvankar; Sundaravadivelu, Pradeep Kumar; Pandit, Gopal; Debnath, Swapna; Thummer, Rajkumar P; Satpati, Priyadarshi; Chatterjee, Sunanda","year":2024,"journal":"ACS infectious diseases, 10(2), 562-581","doi":"10.1021/acsinfecdis.3c00491","pmid":"38294842","tags":["antimicrobial-peptides"],"studyType":"laboratory","evidenceStrength":"preliminary","keyFinding":"All-D-amino acid versions of small cationic antimicrobial peptides (P4C and P5C) were completely resistant to protease degradation while retaining potent antimicrobial activity against ESKAPE pathogens — the most dangerous drug-resistant bacteria. The D-peptides were also noncytotoxic and nonhemolytic, meaning they killed bacteria without harming human cells.\n\nMolecular simulations revealed the mechanism: switching from L to D amino acids barely changed how well the peptides bound bacterial membranes (only ~1 kcal/mol difference), but dramatically reduced binding to proteases by ≥10 kcal/mol. The D-peptides formed inactive complexes with trypsin where the critical catalytic residues couldn't reach the peptide bond to cut it.","whyItMatters":"One of the biggest obstacles to turning antimicrobial peptides into real drugs is that the body's enzymes break them down within minutes. This study shows exactly why mirror-image (D-amino acid) peptides resist this breakdown at the molecular level, and demonstrates that the antimicrobial activity is preserved. Understanding this mechanism could accelerate the design of protease-resistant peptide antibiotics to combat the growing antibiotic resistance crisis.","specificNumbers":"≥10 kcal/mol reduction in protease binding affinity · ~1 kcal/mol marginal change in membrane binding · Complete protease resistance for D-peptides · Active against ESKAPE pathogens · Noncytotoxic and nonhemolytic","methodology":"Laboratory study combining experimental and computational approaches. Researchers synthesized all-D-amino acid versions of cationic antimicrobial heptapeptides (P4C, P5C) and tested their antimicrobial activity against ESKAPE pathogens, protease resistance, cytotoxicity, and hemolytic activity. Molecular dynamics (MD) simulations modeled peptide interactions with both bacterial membrane mimics (SDS micelles) and the protease trypsin to explain the mechanism of protease resistance at the atomic level.","limitations":"This is a laboratory study — the peptides were tested against bacteria in vitro and modeled computationally, not tested in animals or humans. The protease resistance was tested only against trypsin; other proteases may behave differently. The ESKAPE pathogen testing used standard laboratory strains, which may differ from clinical isolates. Pharmacokinetics, biodistribution, and in vivo efficacy remain unknown."},{"rthcId":"RPEP-09211","title":"GLP-1 receptor signaling restores aquaporin 4 subcellular polarization in reactive astrocytes and promotes amyloid β clearance in a mouse model of Alzheimer's disease.","authors":"Sasaki, Kana; Fujita, Hiroki; Sato, Takehiro; Kato, Shunske; Takahashi, Yuya; Takeshita, Yukio; Kanda, Takashi; Saito, Takashi; Saido, Takamori C; Hattori, Satoko; Hozumi, Yasukazu; Yamada, Yuichiro; Waki, Hironori","year":2024,"journal":"Biochemical and biophysical research communications, 741, 151016","doi":"10.1016/j.bbrc.2024.151016","pmid":"39577079","tags":["glp-1-receptor-agonists","neuroprotection"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"20-week subcutaneous liraglutide treatment significantly reduced amyloid-β(1-42) accumulation in cerebral cortex and improved spatial working memory in AppNL-G-F/NL-G-F Alzheimer's mice. Liraglutide restored AQP4 subcellular polarization to perivascular astrocyte endfeet via PKA-mediated phosphorylation, a mechanism confirmed both in vivo and in an immortalized human astrocyte cell line.","whyItMatters":"GLP-1 drugs like liraglutide are already widely prescribed for diabetes and obesity. If they also clear amyloid plaques from the brain through this water channel mechanism, millions of people already taking these peptides may be receiving incidental neuroprotection — and purpose-built applications for Alzheimer's could follow.","specificNumbers":"Focused on amyloid beta (1-42) clearance. Aquaporin 4 localization at astrocyte endfeet perivascular membranes was the key mechanism studied.","methodology":"Animal study using AppNL-G-F/NL-G-F Alzheimer's model mice. GLP-1R expression confirmed via in situ hybridization. Mice treated with subcutaneous liraglutide for 4 and 20 weeks. Assessed: Aβ(1-42) accumulation (immunohistochemistry), spatial working memory (behavioral testing), AQP4 subcellular localization, PKA-mediated AQP4 phosphorylation. Validated in vitro using immortalized human astrocyte cell line with AQP4 cDNA.","limitations":"Animal study using a transgenic Alzheimer's mouse model that may not fully represent human disease. 20-week treatment in mice doesn't directly translate to human dosing timelines. The proposed AQP4/water flux mechanism for Aβ clearance needs direct measurement of glymphatic flow. No human data on this specific mechanism."},{"rthcId":"RPEP-09212","title":"Anxiety and the brain: Neuropeptides as emerging factors.","authors":"Satao, Kiran S; Doshi, Gaurav M","year":2024,"journal":"Pharmacology, biochemistry, and behavior, 245, 173878","doi":"10.1016/j.pbb.2024.173878","pmid":"39284499","tags":["neuroprotection","hormonal-peptides"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Multiple neuropeptide systems contribute to anxiety regulation through distinct mechanisms. Neuropeptide Y is anxiolytic (reduces anxiety), while CRH, substance P, vasopressin, and cholecystokinin are generally anxiogenic (increase anxiety). PACAP modulates stress responses. Each represents a potential drug target for anxiety disorders.","whyItMatters":"Current anxiety medications have significant limitations — SSRIs take weeks to work, benzodiazepines are addictive, and many patients don't respond adequately. Neuropeptide-targeted therapies could offer faster-acting, more precise treatments with potentially fewer side effects.","specificNumbers":"Current treatments include SSRIs, benzodiazepines, non-benzodiazepine anxiolytics, gabapentinoids, and beta-blockers.","methodology":"Narrative review of preclinical and clinical literature on neuropeptide involvement in anxiety. Examines evidence from animal behavioral studies, human genetic association studies, and early-phase clinical trials targeting neuropeptide receptors.","limitations":"Review article with no original data. Much of the neuropeptide anxiety evidence comes from animal models with uncertain human translation. Several neuropeptide-targeted drugs have failed in clinical trials despite strong preclinical data."},{"rthcId":"RPEP-09213","title":"Efficacy and Safety of Escalating the Dose of Oral Semaglutide from 7 to 14 mg: A Single-Center, Retrospective Observational Study.","authors":"Sato, Genki; Uchino, Hiroshi; Hirose, Takahisa","year":2024,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 15(9), 2119-2130","doi":"10.1007/s13300-024-01631-5","pmid":"39110375","tags":["semaglutide","diabetes","dosing"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Dose escalation from 7 mg to 14 mg oral semaglutide produced a significant additional HbA1c reduction of -0.5 ± 0.8% (from 7.4% to 7.0%, p<0.01) and weight loss of -2.0 ± 4.4 kg (p<0.01) over 24 weeks. 41% of patients achieved ≥3% weight reduction. GI disorders occurred in 10.6% (nausea 7.6%), all mild-moderate.","whyItMatters":"Many patients achieve partial but insufficient blood sugar control on the 7 mg dose. This real-world evidence supports that dose escalation to 14 mg provides meaningful additional benefit without a major increase in side effects, helping clinicians and patients make informed dose-adjustment decisions.","specificNumbers":"Dose escalation from 7 mg to 14 mg daily oral semaglutide. Outcomes: HbA1c and body weight changes.","methodology":"Single-center retrospective observational study in Japan. 66 adults with type 2 diabetes who escalated from 7 mg to 14 mg oral semaglutide. Primary endpoint: HbA1c change at 24 weeks post-escalation. Secondary: metabolic parameter changes and adverse event incidence.","limitations":"Small sample size (66 patients). Single-center retrospective design in Japan — results may not generalize to other populations. No control group for comparison. 24-week follow-up may not capture long-term benefits or risks of the higher dose."},{"rthcId":"RPEP-09214","title":"Targeting obesity for therapeutic intervention in heart failure patients.","authors":"Sato, Ryosuke; von Haehling, Stephan","year":2024,"journal":"Expert review of cardiovascular therapy, 22(6), 217-230","doi":"10.1080/14779072.2024.2363395","pmid":"38864827","tags":["glp-1-receptor-agonists","cardiovascular","weight-loss"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"The STEP HFpEF trial demonstrated that semaglutide significantly improved multiple clinical outcomes in obese HFpEF patients with substantial weight loss. The SELECT trial showed significant reduction in cardiovascular and heart failure events in non-diabetic obese patients. Both trials support obesity-targeted GLP-1 therapy as a viable HFpEF treatment strategy.","whyItMatters":"HFpEF has been notoriously difficult to treat — no drug has consistently improved outcomes across all patients. Identifying that the obesity phenotype responds to GLP-1 peptide therapy represents a major shift toward personalized heart failure treatment based on underlying cause.","specificNumbers":"Obesity is one of the leading HFpEF phenotypes, with prevalence growing worldwide.","methodology":"Narrative review with PubMed literature search through April 2024. Examines the pathophysiological links between obesity and HFpEF and synthesizes evidence from key clinical trials (STEP HFpEF, SELECT) and related studies of GLP-1 receptor agonists in heart failure.","limitations":"Review article — no original data. Relies primarily on two landmark trials. Long-term safety and durability of benefits with semaglutide in HFpEF not yet established. The obesity phenotype is heterogeneous, and not all obese HFpEF patients may respond similarly."},{"rthcId":"RPEP-09215","title":"Extracellular vesicle-liposome hybrids via membrane fusion using cell-penetrating peptide-conjugated lipids.","authors":"Sato, Yuya; Zhang, Weixu; Baba, Teruhiko; Chung, Ung-Il; Teramura, Yuji","year":2024,"journal":"Regenerative therapy, 26, 533-540","doi":"10.1016/j.reth.2024.07.006","pmid":"39165408","tags":["cell-penetrating-peptides","peptide-delivery"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Tat-PEG-lipids successfully induced membrane fusion between extracellular vesicles and DPPC/cholesterol liposomes. Dynamic light scattering showed increased apparent size. FRET, confocal microscopy, and TEM confirmed true membrane fusion (not aggregation). Shorter lipid anchors (C9 and C12) with 5 kDa PEG chains produced the cleanest fusion results.","whyItMatters":"Hybrid EV-liposome particles could combine the best of both worlds: EVs' natural targeting ability and biocompatibility with liposomes' drug-loading capacity and manufacturability. A simple peptide-based fusion method could make these advanced drug carriers practical to produce.","specificNumbers":"Not specified — proof-of-concept demonstrating CPP-mediated fusion efficiency.","methodology":"In vitro study. EVs isolated from HEK293T cell culture medium. Liposomes composed of DPPC and cholesterol (1:1 molar ratio). Tat-PEG-lipids synthesized with three lipid anchor lengths (C9, C12, C14) and 5 kDa PEG. Fusion analyzed by dynamic light scattering, fluorescence resonance energy transfer (FRET), confocal laser scanning microscopy, and transmission electron microscopy (TEM).","limitations":"Proof-of-concept in vitro study only. No drug loading or release experiments performed. No cellular uptake or in vivo testing of the hybrid particles. The Tat peptide may trigger immune responses in vivo. Scalability and reproducibility of the fusion process not assessed."},{"rthcId":"RPEP-09216","title":"Effects of the switch from dulaglutide to tirzepatide on glycemic control, body weight, and fatty liver: a retrospective study.","authors":"Sawamura, Toshitaka; Mizoguchi, Ren; Ohmori, Ai; Kometani, Mitsuhiro; Yoneda, Takashi; Karashima, Shigehiro","year":2024,"journal":"Journal of diabetes and metabolic disorders, 23(2), 2105-2113","doi":"10.1007/s40200-024-01472-w","pmid":"39610482","tags":["tirzepatide","glp-1-receptor-agonists","diabetes","liver","weight-loss"],"studyType":"cohort","evidenceStrength":"preliminary","keyFinding":"Switching from dulaglutide to tirzepatide produced average reductions of 1.2% in HbA1c and 3.6 kg in body weight at 6 months. Liver enzymes (AST, ALT, GGT) significantly decreased. HbA1c reduction correlated with higher baseline HbA1c, while weight loss was baseline-independent. Fibrosis-4 index trended toward improvement in those with higher baseline values.","whyItMatters":"Many patients on GLP-1 monotherapy don't achieve optimal control. This study provides real-world evidence that switching to a dual-pathway peptide (tirzepatide) can deliver additional metabolic and liver benefits, which is clinically relevant as physicians decide when and how to escalate therapy.","specificNumbers":"40 patients with type 2 diabetes switched from dulaglutide to tirzepatide. Blood glucose, body weight, and liver function tracked.","methodology":"Single-center retrospective study in Japan. 40 patients with type 2 diabetes who switched from dulaglutide to tirzepatide were analyzed at 3 and 6 months post-switch. Outcomes: HbA1c, body weight, AST, ALT, GGT, and fibrosis-4 index.","limitations":"Very small sample (40 patients). Single-center retrospective design. No control group. 6-month follow-up may miss longer-term effects. Japanese population may not represent other ethnic groups. Specific tirzepatide doses not detailed in abstract."},{"rthcId":"RPEP-09217","title":"MetaCGRP is a high-precision meta-model for large-scale identification of CGRP inhibitors using multi-view information.","authors":"Schaduangrat, Nalini; Khemawoot, Phisit; Jiso, Apisada; Charoenkwan, Phasit; Shoombuatong, Watshara","year":2024,"journal":"Scientific reports, 14(1), 24764","doi":"10.1038/s41598-024-75487-x","pmid":"39433940","tags":["cgrp","migraine"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"MetaCGRP achieved 89.8% accuracy on training data and 79.9% on independent test sets, outperforming conventional ML classifiers. Five potential CGRP inhibitors were identified from Thai herbal pharmacopoeia via MetaCGRP screening combined with molecular docking analysis. A free web server is publicly available for the research community.","whyItMatters":"Developing new CGRP-targeting migraine drugs traditionally costs over a billion dollars and takes years. An accurate computational screening tool could dramatically accelerate the identification of new CGRP inhibitors, potentially including natural products that are cheaper and more accessible than synthetic antibodies.","specificNumbers":"CGRP affects approximately 14-15% of the global population through migraines.","methodology":"Computational drug discovery study. Multiple molecular representation methods coupled with ML algorithms generated baseline models. Multi-view features were extracted and optimized via feature selection to construct the MetaCGRP meta-model. Validated by cross-validation and independent test sets. Applied with molecular docking to screen Thai herbal compounds.","limitations":"Purely computational — no experimental validation of the five identified compounds. Model accuracy of 80% on test data means 1 in 5 predictions could be wrong. Molecular docking scores don't guarantee biological activity. Thai herbal compounds would need extensive pharmacological testing before any clinical application."},{"rthcId":"RPEP-09218","title":"GLP-1 Receptor Agonists and SGLT2 Inhibitors in Type 2 Diabetes: Pleiotropic Cardiometabolic Effects and Add-on Value of a Combined Therapy.","authors":"Scheen, André J","year":2024,"journal":"Drugs, 84(11), 1347-1364","doi":"10.1007/s40265-024-02090-9","pmid":"39342059","tags":["glp-1-receptor-agonists","cardiovascular","kidney","diabetes"],"studyType":"review","evidenceStrength":"strong","keyFinding":"GLP-1RAs primarily reduce atherosclerotic CV events (especially stroke) and renal outcomes, while SGLT2is reduce heart failure hospitalization and kidney disease progression. Post-hoc subgroup analyses suggest a combined GLP-1RA/SGLT2i therapy provides greater cardiorenal protection than monotherapy. The FLOW trial established semaglutide's renal protection. The PRECIDENTD trial will prospectively compare combination vs monotherapy.","whyItMatters":"Cardiovascular and kidney disease are the leading causes of death in type 2 diabetes. Having two drug classes that protect these organs through different mechanisms — and evidence that combining them works better — could fundamentally change how high-risk diabetes patients are managed.","specificNumbers":"Both drug classes improve glucose, weight, and blood pressure while reducing cardiovascular and renal events.","methodology":"Comprehensive narrative review examining published RCTs, cardiovascular outcome trials (CVOTs), and observational studies on GLP-1RAs and SGLT2is. Analyzes mechanistic differences, clinical trial data for individual and combined therapy, and real-world evidence.","limitations":"Review article with no original data. Evidence for combination superiority comes mainly from post-hoc subgroup analyses, not dedicated prospective trials (PRECIDENTD is still ongoing). High cost of combination therapy limits accessibility. Both drug classes remain underused even as monotherapy."},{"rthcId":"RPEP-09219","title":"Effectiveness and tolerability of eptinezumab in treating patients with migraine resistant to conventional preventive medications and CGRP (receptor) antibodies: a multicentre retrospective real-world analysis from Germany.","authors":"Scheffler, Armin; Wenzel, Pauline; Bendig, Merle; Gendolla, Astrid; Basten, Jale; Kleinschnitz, Christoph; Nsaka, Michael; Lindner, Diana; Naegel, Steffen; Burow, Philipp; Fleischmann, Robert; Holle, Dagny","year":2024,"journal":"The journal of headache and pain, 25(1), 79","doi":"10.1186/s10194-024-01788-1","pmid":"38755541","tags":["cgrp","migraine"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Eptinezumab 100 mg significantly reduced MHD, MMD, and AMD in both EM and CM patients. The 30% MHD responder rate strongly correlated with prior CGRP antibody failure: 78.6% (no prior CGRP mAb), 45.0% (failed 1), 32.1% (failed 2), 23.5% (failed 3), p=0.010. Only 10.4% reported mild side effects.","whyItMatters":"Many migraine patients cycle through multiple CGRP antibodies without adequate relief. This study provides the first real-world data on whether switching to eptinezumab (IV route) helps after other CGRP antibodies fail — important information for clinicians making difficult treatment decisions in refractory migraine.","specificNumbers":"Not specified in abstract — multicentre data from German clinical practice.","methodology":"Retrospective real-world analysis of 79 patients (EM n=19, CM n=60) across four German centres. All treated with eptinezumab 100 mg IV. Endpoints: MHD, MMD, and AMD changes at 3 months. Response correlated with number of prior CGRP antibody failures. Bonferroni-corrected significance level α=0.017.","limitations":"Small sample (79 patients). Retrospective design. Only 3-month follow-up. Only the lower eptinezumab dose (100 mg) was used; 300 mg might show better results. German reimbursement policy creates selection bias — eptinezumab was mostly used as last resort. No blinding or control group."},{"rthcId":"RPEP-09220","title":"Persistent effectiveness of CGRP antibody therapy in migraine and comorbid medication overuse or medication overuse headache - a retrospective real-world analysis.","authors":"Scheffler, Armin; Basten, Jale; Menzel, Lennart; Fiebelkorn, Dominik; Becker, Wolfgang Alexander; Breunung, Vincent; Schenk, Hannah; Kleinschnitz, Christoph; Nsaka, Michael; Lindner, Diana; Holle, Dagny","year":2024,"journal":"The journal of headache and pain, 25(1), 109","doi":"10.1186/s10194-024-01813-3","pmid":"38965463","tags":["cgrp","migraine"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Without prior detoxification, CGRP antibodies significantly reduced monthly headache days, migraine days, and acute medication intake across all subgroups. In CM-MOH, 60.6% no longer met MOH criteria; in EM-MO, 89% resolved their overuse. 30% responder rates were comparable between patients with and without medication overuse. Only 15.4% of initially successful CM-MOH patients relapsed. No differences between antibody types.","whyItMatters":"Medication overuse headache is one of the most challenging problems in headache medicine. The traditional requirement to detox before starting preventive therapy causes suffering and is a barrier to care. This study supports skipping detox and starting CGRP antibodies directly, simplifying treatment and reducing patient burden.","specificNumbers":"Not specified in abstract — real-world analysis with sustained outcomes data.","methodology":"Retrospective real-world analysis of 291 migraine patients at a single center. Groups: EM with MO (n=35), EM without MO (n=77), CM with MOH (n=109), CM without MOH (n=70). All started CGRP antibody therapy (erenumab n=173, fremanezumab n=70, galcanezumab n=48) without prior detoxification. Data available for up to 12 months of treatment.","limitations":"Retrospective single-center analysis. No control group or randomization. Different CGRP antibodies used without standardized dosing protocols. Follow-up duration varied. Definition of medication overuse resolution doesn't capture whether patients simply reduced use or truly broke the cycle."},{"rthcId":"RPEP-09221","title":"A lipid-based delivery platform for thermo-responsive delivery of teriparatide.","authors":"Schlosser, Corinna S; Rozek, Wojciech; Mellor, Ryan D; Manka, Szymon W; Morris, Christopher J; Brocchini, Steve; Williams, Gareth R","year":2024,"journal":"International journal of pharmaceutics, 667(Pt A), 124853","doi":"10.1016/j.ijpharm.2024.124853","pmid":"39437847","tags":["parathyroid-hormone","peptide-delivery","bone-health"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Hydrophobic ion pairing achieved >75% teriparatide entrapment in sub-200 nm monodispersed liposomes, outperforming other entrapment methods. Transition temperatures of 38-50°C were obtained by modulating phospholipid composition. In vitro assays demonstrated temperature-dependent release kinetics. Released teriparatide maintained biological activity at the PTH1 receptor.","whyItMatters":"Patient adherence to daily teriparatide injections is poor, limiting the clinical benefit of the only approved bone-building osteoporosis therapy. A delivery system that releases teriparatide in controlled bursts could transform treatment into a longer-acting, more convenient therapy.","specificNumbers":"Teriparatide requires pulsatile release (not continuous) for its bone-building anabolic effect.","methodology":"In vitro formulation study. Hydrophobic ion pairing was used to create a hydrophobic teriparatide complex for liposomal entrapment. Liposomes prepared with various phospholipid compositions to achieve different phase transition temperatures. Characterized by size, dispersity, and entrapment efficiency. Release kinetics tested at different temperatures. Biological activity confirmed using a PTH1 receptor cell-based assay.","limitations":"In vitro proof-of-concept only — no animal or human testing. The practical method of applying heat to trigger release in vivo is not addressed. External heating may be difficult to implement for bone-targeting applications. Long-term stability of the formulation not assessed. Scaling up hydrophobic ion pairing for manufacturing not demonstrated."},{"rthcId":"RPEP-09222","title":"Using Second-Generation Anti-Obesity Medications.","authors":"Schmitz, Sarah H; Aronne, Louis J","year":2024,"journal":"Diabetes spectrum : a publication of the American Diabetes Association, 37(4), 303-312","doi":"10.2337/dsi24-0002","pmid":"39649687","tags":["semaglutide","tirzepatide","weight-loss"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Second-generation anti-obesity medications achieve ~15% average weight loss with lifestyle modifications. Three approved drugs: setmelanotide (monogenic obesity), semaglutide 2.4 mg, and tirzepatide. Semaglutide and tirzepatide are particularly effective when treating concurrent obesity and T2D.","whyItMatters":"Obesity affects over 40% of US adults and first-generation medications offered only modest weight loss. The 15% average weight reduction achieved by these peptide drugs is clinically meaningful — enough to significantly reduce cardiovascular risk, improve diabetes control, and reduce the need for bariatric surgery.","specificNumbers":"Average weight loss of ~15% with lifestyle modifications. Three approved drugs reviewed: setmelanotide, semaglutide 2.4 mg, and tirzepatide.","methodology":"Narrative review examining clinical trial data and therapeutic implications of the three approved second-generation anti-obesity medications.","limitations":"Short review with limited abstract detail. Doesn't discuss cost, access barriers, or long-term safety. Weight regain upon discontinuation not addressed. Setmelanotide applies only to rare monogenic obesity. Real-world effectiveness may differ from clinical trial results."},{"rthcId":"RPEP-09223","title":"The limitation of lipidation: Conversion of semaglutide from once-weekly to once-monthly dosing.","authors":"Schneider, Eric L; Hangasky, John A; Fernández, Rocío Del Valle; Ashley, Gary W; Santi, Daniel V","year":2024,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 121(47), e2415815121","doi":"10.1073/pnas.2415815121","pmid":"39531496","tags":["semaglutide","peptide-delivery","dosing"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Hydrogel microsphere-semaglutide showed an in vivo release half-life of ~36 days in mice. A single subcutaneous dose produced 20% lean-sparing body weight loss over one month, statistically equivalent to twice-daily semaglutide. Pharmacokinetic simulations predicted once-monthly human dosing with Cmin matching weekly dosing but only 75% of the Cmax, potentially reducing adverse effects.","whyItMatters":"Weekly semaglutide injections are a barrier for some patients. A monthly formulation that maintains the same therapeutic minimum while reducing peak drug levels could improve adherence and potentially reduce the gastrointestinal side effects (nausea, vomiting) that cause many patients to discontinue treatment.","specificNumbers":"Cleavable linker designed for ~1 month in vivo release half-life. Single subcutaneous dose tested in mice.","methodology":"Semaglutide conjugated to hydrogel microspheres via a cleavable linker (designed for ~1 month release half-life). Single subcutaneous dose administered to diet-induced obese mice. Pharmacokinetic parameters and bodyweight measured. Results used to simulate human PK for once-monthly dosing. Compared to semaglutide administered twice daily in mice.","limitations":"Mouse study — PK translation to humans is estimated, not proven. The 'lean-sparing' weight loss claim needs verification in human metabolic studies. Manufacturing scalability of hydrogel microspheres not demonstrated. Long-term safety of the hydrogel carrier not assessed. Human clinical trials needed."},{"rthcId":"RPEP-09224","title":"Disproportionality Analysis From World Health Organization Data on Semaglutide, Liraglutide, and Suicidality.","authors":"Schoretsanitis, Georgios; Weiler, Stefan; Barbui, Corrado; Raschi, Emanuel; Gastaldon, Chiara","year":2024,"journal":"JAMA network open, 7(8), e2423385","doi":"10.1001/jamanetworkopen.2024.23385","pmid":"39163046","tags":["semaglutide","liraglutide","peptide-safety","mental-health"],"studyType":"cohort","evidenceStrength":"strong","keyFinding":"Significant disproportionality was detected for semaglutide-associated suicidal ideation (ROR 1.45, 95% CI 1.18-1.77). Signal strengthened in patients co-taking antidepressants (ROR 4.45) or benzodiazepines (ROR 4.07). Remained significant vs comparators: dapagliflozin (ROR 5.56), metformin (ROR 3.86), orlistat (ROR 4.24). No significant signal detected for liraglutide.","whyItMatters":"With tens of millions of people now taking semaglutide worldwide, even a small increased risk of suicidal ideation could affect thousands. This WHO database signal — while not proving causation — warrants urgent investigation given the scale of semaglutide prescribing.","specificNumbers":"Analysis used the WHO global database. Published in JAMA Network Open.","methodology":"Disproportionality analysis using a case-control design in the WHO global database (VigiBase) of suspected adverse drug reactions. Reporting odds ratios (ROR) and Bayesian information components (IC) calculated for semaglutide and liraglutide vs all other medications. Sensitivity analyses included patients co-taking antidepressants/benzodiazepines and comparisons with dapagliflozin, metformin, and orlistat.","limitations":"Disproportionality analysis cannot establish causation — only signal detection. WHO VigiBase has reporting bias (increased media attention may drive more semaglutide reports). No individual patient-level data to assess confounders. Many semaglutide users have obesity/diabetes, which are independently associated with depression. Signal was found for semaglutide but not liraglutide (both GLP-1 agonists), which is mechanistically puzzling."},{"rthcId":"RPEP-09225","title":"Semaglutide and NYHA Functional Class in Obesity-Related Heart Failure With Preserved Ejection Fraction: The STEP-HFpEF Program.","authors":"Schou, Morten; Petrie, Mark C; Borlaug, Barry A; Butler, Javed; Davies, Melanie J; Kitzman, Dalane W; Shah, Sanjiv J; Verma, Subodh; Patel, Shachi; Chinnakondepalli, Khaja M; Harring, Signe; Abildstrøm, Steen Z; Liisberg, Karoline; Kosiborod, Mikhail N","year":2024,"journal":"Journal of the American College of Cardiology, 84(3), 247-257","doi":"10.1016/j.jacc.2024.04.038","pmid":"38913004","tags":["semaglutide","cardiovascular","weight-loss"],"studyType":"RCT","evidenceStrength":"strong","keyFinding":"Semaglutide improved NYHA class in 32.6% vs 21.5% placebo (OR 2.20, P<0.001). Deterioration occurred in only 2.1% vs 5.2% (OR 0.36, P=0.003). KCCQ-CSS improvement was especially pronounced in NYHA III/IV (10.5 points vs 6.0 in class II). Weight loss was consistent (~8.4%) regardless of baseline NYHA class. Consistent improvements in 6MWD, CRP, and NT-proBNP across all categories.","whyItMatters":"NYHA functional class is one of the most important clinical measures in heart failure — it directly reflects how heart failure limits daily life. Showing that semaglutide improves functional status, with the biggest gains in the most limited patients, demonstrates meaningful clinical benefit beyond just weight loss.","specificNumbers":"Analysis from the STEP-HFpEF program. NYHA functional class ranges from I (no limitation) to IV (severe limitation).","methodology":"Prespecified pooled analysis of STEP-HFpEF and STEP-HFpEF DM — two international, double-blind, placebo-controlled RCTs. 1,145 participants with obesity-related HFpEF randomized to semaglutide 2.4 mg weekly or placebo for 52 weeks. Primary outcome: change in NYHA functional class. Secondary: KCCQ-CSS, 6MWD, bodyweight, CRP, NT-proBNP by baseline NYHA class.","limitations":"Post-hoc pooled analysis — though prespecified, it combines two trials with slightly different populations (with and without T2D). NYHA classification is somewhat subjective. 52-week follow-up may not capture durability of functional improvement. The sickest patients (NYHA IV) were underrepresented."},{"rthcId":"RPEP-09226","title":"Impact of Specific Bioactive Collagen Peptides on Joint Discomforts in the Lower Extremity during Daily Activities: A Randomized Controlled Trial.","authors":"Schulze, Claas; Schunck, Michael; Zdzieblik, Denise; Oesser, Steffen","year":2024,"journal":"International journal of environmental research and public health, 21(6)","doi":"10.3390/ijerph21060687","pmid":"38928934","tags":["collagen-peptides","bone-health"],"studyType":"RCT","evidenceStrength":"moderate","keyFinding":"5 g daily SCP supplementation for 12 weeks significantly reduced pain at rest (p=0.018) and during walking (p=0.032) per physician evaluation. Participants reported significantly less pain climbing stairs (p=0.040) and kneeling (p=0.014) compared to placebo.","whyItMatters":"Joint pain is one of the most common health complaints, particularly as people age. An accessible, well-tolerated supplement that can reduce pain during everyday activities like walking and stair climbing could meaningfully improve quality of life for millions of people.","specificNumbers":"182 participants. 5 g collagen peptides (CP-G) vs. placebo (P-G) for 12 weeks. Pain at rest and during daily activities measured.","methodology":"Randomized, placebo-controlled trial. 182 healthy adults (18+ years) with functional knee and hip pain during daily activities. Randomized to 5 g specific collagen peptides (CP-G) or placebo (P-G) for 12 weeks. Pain assessed at baseline and 12 weeks by physician and participants using 10-point numeric rating scale (NRS).","limitations":"12-week duration may be too short to detect long-term effects or cartilage structural changes. Pain assessment relies on subjective rating scales. Specific composition of the collagen peptides was standardized but may not apply to all collagen supplements. No imaging to confirm structural joint changes."},{"rthcId":"RPEP-09227","title":"A cleavable peptide adapter augments the activity of targeted toxins in combination with the glycosidic endosomal escape enhancer SO1861.","authors":"Schulze, Finn J; Asadian-Birjand, Mazdak; Pradela, Michael; Niesler, Nicole; Nagel, Gregor; Fuchs, Hendrik","year":2024,"journal":"BMC biotechnology, 24(1), 24","doi":"10.1186/s12896-024-00854-5","pmid":"38685061","tags":["peptide-drug-conjugates","cancer","peptide-delivery"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"The peptide adapter alone enhanced cytotoxicity 12-fold. SO1861 alone enhanced it 430-fold. Combined: 4,300-fold enhancement with 51-fold increased specificity for target cancer cells. The adapter augments SO1861-mediated endosomal escape while maintaining tumor specificity.","whyItMatters":"Targeted toxins promise to kill cancer cells while sparing healthy tissue, but most fail clinically because they get trapped in endosomes. This dual approach — combining a peptide adapter with an endosomal escape molecule — could make targeted cancer toxins clinically viable for the first time.","specificNumbers":"Not specified — proof-of-concept study demonstrating enhanced cytotoxic activity.","methodology":"In vitro study. A molecular adapter (cell-penetrating peptide + two cleavable peptides) was inserted into a targeted toxin between dianthin (ribosome-inactivating protein) and EGF (targeting ligand). Cell viability assays measured cytotoxicity on target cells with and without SO1861 endosomal escape enhancer.","limitations":"In vitro study only — no animal or human data. The dramatic fold-changes may not translate to in vivo settings where pharmacokinetics, biodistribution, and immune responses add complexity. Long-term toxicity of the combined approach unknown. Manufacturing complexity of multi-component constructs could be challenging."},{"rthcId":"RPEP-09228","title":"Anti-CGRP and Anti-CGRP Receptor Monoclonal Antibodies for Migraine Prophylaxis: Retrospective Observational Study on 209 Patients.","authors":"Schweiger, Vittorio; Bellamoli, Paola; Taus, Francesco; Gottin, Leonardo; Martini, Alvise; Nizzero, Marta; Bonora, Eleonora; Del Balzo, Giovanna; Donadello, Katia; Secchettin, Erica; Finco, Gabriele; Santis, Daniele De; Polati, Enrico","year":2024,"journal":"Journal of clinical medicine, 13(4)","doi":"10.3390/jcm13041130","pmid":"38398444","tags":["cgrp","migraine"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"In 205 analyzed patients, erenumab and galcanezumab showed statistically significant improvements in MIDAS, HIT-6, monthly migraine days, and acute medication days. 17.5% reported adverse events (injection site pain, nausea, constipation, fatigue). Only 2.4% discontinued due to AEs, 7.3% for lack of efficacy.","whyItMatters":"Real-world effectiveness data complements clinical trial findings by showing how these drugs perform in typical clinical practice — with diverse patients, concomitant medications, and varying compliance patterns that clinical trials can't fully capture.","specificNumbers":"209 patients. Three drugs: fremanezumab, galcanezumab, and erenumab. Prescribed between 2019 and 2022.","methodology":"Retrospective observational study of 209 migraine patients prescribed subcutaneous CGRP antibodies (erenumab, galcanezumab, or fremanezumab) between 2019-2022. Outcomes: MIDAS, HIT-6, monthly migraine days (MMD), and monthly acute medication days (MAD). Could use concomitant acute or prophylactic medications.","limitations":"Retrospective observational design without a control group. Fremanezumab's non-significant results likely due to small sample rather than true inferiority. No head-to-head statistical comparison between the three antibodies. Variable follow-up periods. Concomitant medication use may confound results."},{"rthcId":"RPEP-09229","title":"Illuminating the neuropeptide Y4 receptor and its ligand pancreatic polypeptide from a structural, functional, and therapeutic perspective.","authors":"Schüß, Corinna; Behr, Victoria; Beck-Sickinger, Annette G","year":2024,"journal":"Neuropeptides, 105, 102416","doi":"10.1016/j.npep.2024.102416","pmid":"38430725","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09230","title":"The Effect of Semaglutide on Mortality and COVID-19-Related Deaths: An Analysis From the SELECT Trial.","authors":"Scirica, Benjamin M; Lincoff, A Michael; Lingvay, Ildiko; Bogdanski, Pawel; Buscemi, Silvio; Colhoun, Helen; Craciun, Anca-Elena; Ezhov, Marat; Hardt-Lindberg, Søren; Kleist Jeppesen, Ole; Matos, Ana Laura S A; Node, Koichi; Schiele, Francois; Toplak, Hermann; van Beek, André; Weeke, Peter E; Wiviott, Stephen D; Deanfield, John; Ryan, Donna","year":2024,"journal":"Journal of the American College of Cardiology, 84(17), 1632-1642","doi":"10.1016/j.jacc.2024.08.007","pmid":"39217559","tags":["semaglutide","cardiovascular","weight-loss","peptide-safety"],"studyType":"RCT","evidenceStrength":"strong","keyFinding":"Semaglutide 2.4 mg vs placebo reduced all-cause death (HR 0.81, CI 0.71-0.93), non-CV death (HR 0.77, CI 0.62-0.95), and infectious death (HR 0.71, CI 0.51-0.98). Among COVID-19 patients, semaglutide reduced COVID deaths (HR 0.66, CI 0.44-0.96) and serious COVID events (232 vs 277, p=0.04). CV death trended lower (HR 0.85, CI 0.71-1.01).","whyItMatters":"This is the first major trial to show a GLP-1 peptide drug reduces all-cause mortality in a large population. The unexpected finding of fewer infectious and COVID-19 deaths suggests semaglutide may have anti-inflammatory or immune-modulating effects beyond weight loss and cardiovascular protection.","specificNumbers":"17,604 participants randomized. Semaglutide 2.4 mg vs. placebo. Outcomes included all-cause death, CV death, non-CV death, and COVID-19 death.","methodology":"Pre-specified analysis of the SELECT trial: double-blind RCT randomizing 17,604 participants ≥45 years, BMI ≥27, with established CV disease but without diabetes to semaglutide 2.4 mg weekly or placebo. Mean follow-up 3.3 years. All deaths adjudicated and categorized into CV, non-CV, and specific subcategories including COVID-19.","limitations":"COVID-19 analysis is observational within an RCT — semaglutide didn't prevent COVID infection, only reduced severity. The CV death reduction didn't reach statistical significance (p=0.07). Death subcategory analyses have smaller numbers and should be considered exploratory. Trial excluded diabetic patients, limiting generalizability."},{"rthcId":"RPEP-09231","title":"Imaging and Circulating Biomarker-Defined Cardiac Pathology in Pulmonary Tuberculosis: A Systematic Review.","authors":"Scopazzini, Marcello S; Hill, Katherine J; Majonga, Edith D; Zenner, Dominik; Ayles, Helen; Shah, Anoop S V","year":2024,"journal":"Global heart, 19(1), 84","doi":"10.5334/gh.1369","pmid":"39524989","tags":["natriuretic-peptides","cardiovascular"],"studyType":"meta-analysis","evidenceStrength":"moderate","keyFinding":"Pericardial effusion prevalence: 14.1-55.9% on echocardiography. LV systolic impairment: 0-4.25%. Myocardial inflammation: 0.6-21.8% on PET-CT. Only 1 study assessed cardiac biomarkers (BNP, troponin, CK-MB). Elevated troponin found in 246/800 patients. No CTCA studies identified.","whyItMatters":"TB kills 1.3 million people annually and is associated with increased long-term cardiovascular mortality. Understanding how TB damages the heart — and using biomarkers like BNP for early detection — could help reduce this excess mortality through timely cardiac monitoring and intervention.","specificNumbers":"Not specified — systematic review synthesizing available evidence.","methodology":"Systematic review of databases for studies evaluating cardiac pathology in PTB patients. Included studies using echocardiography, cardiac MRI, PET-CT, CT coronary angiography, cardiac troponin, and B-type natriuretic peptides. Seven studies with 1,333 participants met inclusion criteria.","limitations":"Only 7 studies met inclusion criteria — very limited evidence base. Heterogeneous study designs and populations. Only 1 study assessed cardiac biomarkers. No coronary artery disease imaging data. Most studies used echocardiography, which may miss subtle myocardial pathology."},{"rthcId":"RPEP-09232","title":"Effect of Weight Loss Interventions on the Symptomatic Burden and Biomarkers of Polycystic Ovary Syndrome : A Systematic Review of Randomized Controlled Trials.","authors":"Scragg, Jadine; Hobson, Alice; Willis, Lia; Taylor, Kathryn S; Dixon, Sharon; Jebb, Susan A","year":2024,"journal":"Annals of internal medicine, 177(12), 1664-1674","doi":"10.7326/M23-3179","pmid":"39496172","tags":["weight-loss","hormonal-peptides","glp-1-receptor-agonists"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Weight loss interventions significantly improved HOMA-IR (-0.45, CI -0.75 to -0.15), free androgen index (-2.03, CI -3.0 to -1.07), and menstrual frequency (+2.64, CI 0.65-4.63). Nine trials used GLP-1 agonists. No significant effect on hirsutism or quality of life. Published in Annals of Internal Medicine.","whyItMatters":"PCOS affects 8-13% of women of reproductive age and is closely linked to obesity. While guidelines recommend weight loss, this is the most comprehensive evidence to date showing which PCOS features actually improve — and which don't — validating weight loss as a core PCOS treatment strategy.","specificNumbers":"Databases searched from inception through June 2024. RCTs comparing weight loss interventions to usual care in PCOS.","methodology":"Systematic review and meta-analysis. Searched MEDLINE, Embase, PsycINFO, CINAHL, Cochrane, and Web of Science through June 2024. Included RCTs comparing weight loss interventions to usual care in PCOS. 29 comparisons, 1,529 participants. Random-effects meta-analysis with Knapp-Hartung adjustment. Risk of bias assessed for each study.","limitations":"High statistical heterogeneity across interventions and comparators. Most studies had high or some risk of bias. GLP-1 trials not analyzed separately in the primary analysis. No evidence of hirsutism or QoL improvement, though may be due to limited power. Short study durations may miss long-term benefits."},{"rthcId":"RPEP-09233","title":"Glycemia reduction in type 2 diabetes-Hypoglycemia outcomes: A randomized clinical trial.","authors":"Seaquist, Elizabeth R; Phillips, Lawrence S; Ghosh, Alokananda; Baker, Chelsea; Bergenstal, Richard M; Crandall, Jill P; Goland, Robin S; Gramzinski, Michaela R; Hox, Sophia H; Hsia, Daniel S; Johnson, Mary L; Lachin, John M; Raskin, Philip; Valencia, Willy M; Waltje, Andrea H; Younes, Naji","year":2024,"journal":"PloS one, 19(11), e0309907","doi":"10.1371/journal.pone.0309907","pmid":"39546502","tags":["glp-1-receptor-agonists","diabetes","peptide-safety"],"studyType":"RCT","evidenceStrength":"strong","keyFinding":"Severe hypoglycemia rates: glargine 0.8%, glimepiride 1.3%, liraglutide 0.5%, sitagliptin 0.3% (p<0.05). Hypoglycemic symptoms: glargine 54.2%, glimepiride 68.3%, liraglutide 32.4%, sitagliptin 29.1% (p<0.001). Liraglutide and sitagliptin had significantly less hypoglycemia than glimepiride and glargine.","whyItMatters":"Hypoglycemia is the most feared acute complication of diabetes treatment. This head-to-head comparison in a large trial provides definitive evidence that GLP-1 peptide agonists cause far less hypoglycemia than older medications, helping physicians choose safer second-line therapies.","specificNumbers":"5,047 randomized, 4,830 in per-protocol analysis. HbA1c entry threshold >7.5% (>58.5 mmol/mol).","methodology":"Randomized controlled trial of 5,047 T2D patients with HbA1c >7.5% on metformin, randomized to add glargine insulin, glimepiride, liraglutide, or sitagliptin. Per-protocol analysis of 4,830 who attended ≥1 post-baseline visit. Severe hypoglycemia tracked throughout. Hypoglycemic symptoms assessed quarterly. Glucose <70 mg/dL monitored in glargine/glimepiride groups.","limitations":"Glucose monitoring was done differently across groups — only glargine and glimepiride groups measured glucose <70 mg/dL, limiting cross-group biomarker comparison. Hypoglycemic symptoms are patient-reported and may vary in sensitivity. Rescue insulin was added when needed, potentially affecting later comparisons."},{"rthcId":"RPEP-09234","title":"Comparing the biological activity and composition of Cerebrolysin with other peptide preparations.","authors":"Seidl, Lisa-Franziska; Aigner, Ludwig","year":2024,"journal":"Journal of medicine and life, 17(1), 24-27","doi":"10.25122/jml-2024-0129","pmid":"38737662","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09235","title":"A randomized phase 2b trial examined the effects of the glucagon-like peptide-1 and glucagon receptor agonist cotadutide on kidney outcomes in patients with diabetic kidney disease.","authors":"Selvarajah, Viknesh; Robertson, Darren; Hansen, Lars; Jermutus, Lutz; Smith, Kirsten; Coggi, Angela; Sánchez, José; Chang, Yi-Ting; Yu, Hongtao; Parkinson, Joanna; Khan, Anis; Chung, H Sophia; Hess, Sonja; Dumas, Richard; Duck, Tabbatha; Jolly, Simran; Elliott, Tom G; Baker, John; Lecube, Albert; Derwahl, Karl-Michael; Scott, Russell; Morales, Cristobal; Peters, Carl; Goldenberg, Ronald; Parker, Victoria E R; Heerspink, Hiddo J L","year":2024,"journal":"Kidney international, 106(6), 1170-1180","doi":"10.1016/j.kint.2024.08.023","pmid":"39218393","tags":["glp-1-receptor-agonists","kidney","diabetes"],"studyType":"RCT","evidenceStrength":"moderate","keyFinding":"Cotadutide dose-dependently reduced UACR at week 14: 300 μg (-43.9%, CI -54.7 to -30.6) and 600 μg (-49.9%, CI -59.3 to -38.4) vs placebo. Effects sustained at 26 weeks. Safety of cotadutide 600 μg comparable to semaglutide. Serious AEs balanced across arms. 46.8% on concomitant SGLT2i.","whyItMatters":"Diabetic kidney disease is the leading cause of kidney failure worldwide. While GLP-1 agonists and SGLT2 inhibitors offer some kidney protection, cotadutide's dual mechanism (adding glucagon receptor activation) produced nearly 50% albuminuria reduction — potentially a more powerful kidney-protective approach for high-risk patients.","specificNumbers":"Patients with eGFR 20-90 mL/min/1.73m² and UACR >50 mg/g. 26-week treatment. 1:1:1:1:1 randomization.","methodology":"Phase 2b, randomized, double-blind (cotadutide vs placebo), open-label (semaglutide) trial. 248 patients with T2D and CKD (eGFR 20-90, UACR >50 mg/g) randomized 1:1:1:1:1 to cotadutide 100, 300, or 600 μg daily, placebo daily, or semaglutide 1 mg weekly for 26 weeks. Co-primary endpoints: absolute and percentage UACR change from baseline to week 14.","limitations":"Phase 2b — not powered for hard kidney endpoints (progression to dialysis, eGFR decline). UACR is a surrogate marker. Open-label semaglutide arm may introduce bias. 26-week duration may not reflect long-term kidney protection. Cotadutide requires daily injection vs semaglutide's weekly dosing."},{"rthcId":"RPEP-09236","title":"Patients' Experiences During the Long Journey Before Initiating Migraine Prevention with a Calcitonin Gene-Related Peptide (CGRP) Monoclonal Antibody (mAb).","authors":"Seng, Elizabeth; Lampl, Christian; Viktrup, Lars; Lenderking, William R; Karn, Hayley; Hoyt, Margaret; Kim, Gilwan; Ruff, Dustin; Ossipov, Michael H; Vincent, Maurice","year":2024,"journal":"Pain and therapy, 13(6), 1589-1615","doi":"10.1007/s40122-024-00652-z","pmid":"39298053","tags":["cgrp","migraine"],"studyType":"cohort","evidenceStrength":"preliminary","keyFinding":"500 patients surveyed (250 EM, 250 CM, 90% female). Mean 4.1 healthcare providers seen before diagnosis. 71% suspected migraine before diagnosis. 31% reluctant to seek care. 20% initially misdiagnosed. Prior preventives included anticonvulsants (61%), antidepressants (44%), blood pressure meds (43%), botulinum toxin (17%). Most discontinuations due to lack of efficacy or side effects.","whyItMatters":"Understanding the patient journey reveals systemic barriers to effective migraine care. If patients see 4+ doctors before diagnosis and many are reluctant to seek help, CGRP antibody treatments — though effective — may not reach those who need them most without addressing these upstream problems.","specificNumbers":"Survey of patients in the Emgality Patient Support Program (2022).","methodology":"Cross-sectional self-reported online survey of 500 subjects (250 episodic, 250 chronic migraine) enrolled in Lilly's Emgality Patient Support Program in 2022. Collected data on migraine history, diagnostic journey, healthcare interactions, and treatments before CGRP antibody initiation.","limitations":"Selection bias — survey participants were already in a manufacturer's support program and may not represent all migraine patients. Self-reported data subject to recall bias. Sponsored by Eli Lilly (Emgality manufacturer). Cross-sectional design cannot establish causation for treatment delays."},{"rthcId":"RPEP-09237","title":"Low-molecular-weight collagen peptides supplement promotes a healthy skin: A randomized, double-blinded, placebo-controlled study.","authors":"Seong, Seol Hwa; Lee, Young In; Lee, Joohee; Choi, Sooyeon; Kim, In Ah; Suk, Jangmi; Jung, Inhee; Baeg, Chaemin; Kim, Jinhak; Oh, Dongchan; Lee, Ju Hee","year":2024,"journal":"Journal of cosmetic dermatology, 23(2), 554-562","doi":"10.1111/jocd.16026","pmid":"37822045","tags":["collagen-peptides","skin-health"],"studyType":"RCT","evidenceStrength":"moderate","keyFinding":"Collagen peptides significantly improved skin roughness, wrinkle peak-to-valley values, maximum peak height, and average maximum wrinkle height vs placebo. Overall, net, and biological elasticity significantly improved at week 12. Skin hydration and whitening (melanin, erythema) also significantly improved. Zero adverse events reported.","whyItMatters":"Skin aging is a universal concern, and collagen peptide supplements are a massive consumer market. This controlled trial provides rigorous evidence that oral collagen peptides can measurably improve multiple objective skin parameters — not just subjective appearance.","specificNumbers":"100 participants randomly assigned. Measured parameters: skin wrinkles, hydration, and elasticity.","methodology":"Randomized, double-blinded, placebo-controlled study. 100 healthy adults randomly assigned to low-molecular-weight collagen peptides or placebo. Skin parameters measured at baseline and weeks 4, 8, and 12: wrinkles, elasticity, hydration, melanin index, and erythema index.","limitations":"Relatively small sample (100 participants). Specific dose not provided in abstract. Low-molecular-weight formulation may not represent all collagen supplements. 12 weeks may not show maximum benefit. No histological confirmation of skin structural changes."},{"rthcId":"RPEP-09238","title":"Oral consumption of Bonito fish-derived elastin peptide (VGPG Elastin® ) improves biophysical properties in aging skin: A randomized, double-blinded, placebo-controlled study.","authors":"Seong, Seol Hwa; Lee, Young In; Lee, Joohee; Suk, Jangmi; Kim, In Ah; Baeg, Chaemin; Kim, Jinhak; Lee, Ju Hee","year":2024,"journal":"Skin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging (ISSI), 30(3), e13634","doi":"10.1111/srt.13634","pmid":"38481080","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09239","title":"Peptide Receptor Radionuclide Therapy in Advanced Refractory Meningiomas: Efficacy and Toxicity in a Long Follow-up.","authors":"Severi, Stefano; Grassi, Ilaria; Bongiovanni, Alberto; Nicolini, Silvia; Marini, Irene; Arpa, Donatella; Ranallo, Nicoletta; Azzali, Irene; Di Iorio, Valentina; Sarnelli, Anna; Manuela, Monti; Amadori, Elena; Fabbri, Lucia; Bartolini, Daniela; Tosatto, Luigino; Di Meco, Francesco; Gurrieri, Lorena; Riva, Nada; Calabro, Luana; Matteucci, Federica; Paganelli, Giovanni; Sansovini, Maddalena","year":2024,"journal":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 65(9), 1409-1415","doi":"10.2967/jnumed.123.266956","pmid":"39142827","tags":["somatostatin","cancer","radionuclide-therapy"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"42 patients treated with PRRT (5 with 90Y-DOTATOC, 37 with 177Lu-DOTATATE). Disease control rate: 57%. Median PFS: 16 months. Median OS: 36 months (63-month follow-up). 6 patients retreated with 177Lu-PRRT (retreatment PFS: 6.5 months, OS: 17 months). Only 1 treatment discontinuation for grade 3 platelet toxicity.","whyItMatters":"Recurrent meningiomas after surgery and radiation have essentially no effective third-line treatment options. PRRT targeting somatostatin receptors provides a viable therapeutic option for these patients, with meaningful disease control and a favorable side effect profile.","specificNumbers":"Long-term follow-up data. Diagnosis with 68Ga-DOTA-octreotide PET/CT; treatment with 90Y/177Lu-DOTA-octreotide.","methodology":"Single-center retrospective cohort study. 42 meningioma patients with radiologic recurrence after surgery and radiotherapy treated with 90Y-DOTATOC (1.1-5.5 GBq) or 177Lu-DOTATATE (3.7-5.5 GBq) in ~4 cycles (Oct 2009-Oct 2021). All confirmed somatostatin receptor overexpression on 68Ga-DOTATOC PET/CT or 111In-octreotide scan.","limitations":"Retrospective single-center study. No control group. Mixed use of two different radioisotopes (90Y and 177Lu). Small retreatment cohort (n=6). Disease control doesn't always mean tumor shrinkage — includes stable disease. Selection bias toward patients with strong somatostatin receptor expression."},{"rthcId":"RPEP-09240","title":"Risk of Hepatocellular Carcinoma with Glucagon-like Peptide-1 receptor agonist treatment in patients: a systematic review and meta-analysis.","authors":"Shabil, Muhammed; Khatib, Mahalaqua Nazli; Ballal, Suhas; Bansal, Pooja; Tomar, Balvir S; Ashraf, Ayash; Kumar, M Ravi; Sinha, Aashna; Rawat, Pramod; Gaidhane, Abhay M; Sah, Sanjit; Daniel, Afukonyo Shidoiku; Yappalparvi, Ambanna; Bushi, Ganesh","year":2024,"journal":"BMC endocrine disorders, 24(1), 246","doi":"10.1186/s12902-024-01775-2","pmid":"39551761","tags":["glp-1-receptor-agonists","liver","cancer"],"studyType":"meta-analysis","evidenceStrength":"moderate","keyFinding":"GLP-1RAs vs insulin/no GLP-1RA: pooled HR 0.41 (CI 0.28-0.55), with considerable heterogeneity (I²=74%). GLP-1RAs vs metformin: HR 0.99 (not significant). GLP-1RAs vs DPP-4 inhibitors: HR 1.05 (not significant). GLP-1RAs vs sulfonylureas: HR 0.78 (CI 0.65-0.93).","whyItMatters":"Liver cancer is increasing globally, driven partly by the metabolic liver disease epidemic in diabetic patients. If GLP-1 drugs reduce HCC risk — even partly through improved liver health — this adds another compelling reason to prescribe these peptide medications for at-risk diabetic patients.","specificNumbers":"Not specified in abstract — meta-analysis of available studies.","methodology":"Systematic review and meta-analysis of PubMed, EMBASE, and Web of Science through August 2024. Eight studies evaluating HCC incidence in T2DM patients on GLP-1RAs vs other therapies included. Random-effects model used for pooled hazard ratios. Heterogeneity assessed via I² statistic.","limitations":"Considerable heterogeneity (I²=74%). Observational studies are subject to confounding — GLP-1RA users may differ systematically from insulin users. No randomized controlled trial data. The comparison to metformin showing no difference suggests the benefit may not be GLP-1-specific. Publication bias not fully assessed."},{"rthcId":"RPEP-09241","title":"Semaglutide and diuretic use in obesity-related heart failure with preserved ejection fraction: a pooled analysis of the STEP-HFpEF and STEP-HFpEF-DM trials.","authors":"Shah, Sanjiv J; Sharma, Kavita; Borlaug, Barry A; Butler, Javed; Davies, Melanie; Kitzman, Dalane W; Petrie, Mark C; Verma, Subodh; Patel, Shachi; Chinnakondepalli, Khaja M; Einfeldt, Mette N; Jensen, Thomas J; Rasmussen, Søren; Asleh, Rabea; Ben-Gal, Tuvia; Kosiborod, Mikhail N","year":2024,"journal":"European heart journal, 45(35), 3254-3269","doi":"10.1093/eurheartj/ehae322","pmid":"38739118","tags":["semaglutide","cardiovascular","weight-loss"],"studyType":"RCT","evidenceStrength":"strong","keyFinding":"Weight loss consistent across diuretic groups (-6.9% to -8.8%, interaction P=0.39). KCCQ improvement greater in loop diuretic users (+9.3 vs +4.7 points, P=0.042). Loop diuretic dose decreased 17% with semaglutide vs +2.4% with placebo (P<0.0001). Semaglutide: OR 2.67 for dose reduction, OR 0.35 for dose increase. All secondary endpoints consistent across diuretic subgroups.","whyItMatters":"Diuretic reduction in heart failure is a meaningful clinical outcome — it suggests improved fluid balance and cardiac function, not just symptom masking. That semaglutide allows patients to reduce their diuretic doses while improving symptoms indicates genuine disease modification.","specificNumbers":"1,145 patients pooled from STEP-HFpEF and STEP-HFpEF-DM. Published in European Heart Journal.","methodology":"Prespecified pooled analysis of STEP-HFpEF and STEP-HFpEF-DM (n=1,145). Participants stratified by baseline diuretic use: no diuretic (n=220), non-loop only (n=223), loop ≤40 mg furosemide equivalents (n=174), loop >40 mg (n=528). Assessed efficacy endpoints and loop diuretic dose changes over 52 weeks.","limitations":"Subgroup analysis — though prespecified, subgroup sizes vary. The diuretic dose reduction doesn't necessarily mean improved heart failure per se (could reflect weight-related fluid loss). Open-label nature of diuretic adjustments may introduce bias. 52-week follow-up may not capture long-term diuretic trajectory."},{"rthcId":"RPEP-09242","title":"Enhancing the Therapeutic Efficacy of GLP-1 for Hyperglycemia Treatment: Overcoming Barriers of Oral Gene Therapy with Taurocholic Acid-Conjugated Protamine Sulfate and Calcium Phosphate.","authors":"Shahriar, S M Shatil; An, Jeong Man; Surwase, Sachin S; Lee, Dong Yun; Lee, Yong-Kyu","year":2024,"journal":"ACS nanoscience Au, 4(3), 194-204","doi":"10.1021/acsnanoscienceau.3c00035","pmid":"38912289","tags":["glp-1-receptor-agonists","peptide-delivery"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Single oral GENE/PTCA dose induced endogenous GLP-1 and insulin production in mice. Maintained normoglycemia for a prolonged period. Higher therapeutic efficacy than FDA-approved injectable semaglutide and liraglutide in preclinical models. More effective than 20 insulin injections. High safety profile across all toxicology assessments.","whyItMatters":"If a single oral dose could replace daily/weekly injections for diabetes treatment, it would be transformative for the hundreds of millions of people with diabetes worldwide. Oral gene therapy that makes the body produce its own GLP-1 could bypass all the barriers of peptide drug delivery.","specificNumbers":"System uses ASBT pathway for intestinal absorption. Tested in animal models of hyperglycemia.","methodology":"Animal study. GLP-1 gene plasmid formulated with taurocholic acid-conjugated protamine sulfate and calcium phosphate (PTCA carrier). Single oral dose administered to hyperglycemic mice at different formulation doses. PK/PD endpoints: GLP-1 levels, insulin production, blood glucose, insulin sensitivity, glucose tolerance. Compared to injectable semaglutide and liraglutide. Comprehensive toxicology assessment performed.","limitations":"Mouse study — human translation is far from certain. Claims of outperforming semaglutide/liraglutide need verification in larger, independent studies. Gene therapy safety concerns (insertional mutagenesis, immune responses) not fully addressed for long-term use. Duration of effect not precisely defined. No comparison to oral semaglutide."},{"rthcId":"RPEP-09243","title":"Cardiac natriuretic peptides.","authors":"Shalmi, Theodor W; Jensen, Anne Sophie B; Goetze, Jens P","year":2024,"journal":"Advances in clinical chemistry, 122, 115-139","doi":"10.1016/bs.acc.2024.06.009","pmid":"39111961","tags":["natriuretic-peptides","cardiovascular"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Cardiac natriuretic peptides (ANP, BNP) serve dual clinical roles: as diagnostic biomarkers for heart failure (BNP and NT-proBNP blood tests are standard of care) and as therapeutic targets (sacubitril/valsartan inhibits neprilysin to increase natriuretic peptide levels). The system encompasses peptide hormones, specific receptors (NPR-A, NPR-B, NPR-C), and processing enzymes.","whyItMatters":"BNP blood tests are now one of the most commonly ordered cardiac tests worldwide, used daily in emergency rooms and cardiology clinics to diagnose heart failure. Understanding the natriuretic peptide system is essential for anyone working in cardiovascular medicine.","specificNumbers":"Four decades of research. BNP and NT-proBNP are the main clinical biomarkers.","methodology":"Narrative review covering the biochemistry, physiology, and pathophysiology of the cardiac natriuretic peptide system. Discusses molecular components, quantitative methods, and clinical applications in heart failure.","limitations":"Introductory review aimed at non-specialists — may lack depth for experts in the field. Does not cover emerging natriuretic peptide applications (cancer, metabolism) in detail. Focuses primarily on established clinical applications rather than cutting-edge research."},{"rthcId":"RPEP-09244","title":"Glucagon-like peptide-1 receptor agonists in adolescents with overweight or obesity with or without type 2 diabetes multimorbidity-a systematic review and network meta-analysis.","authors":"Shamim, Muhammad Aaqib; Patil, Amol N; Amin, Ulfat; Roy, Tuli; Tiwari, Krishna; Husain, Noor; Kumar, Jogender; Chenchula, Santenna; Rao, Priyanka; Ganesh, Venkata; Varthya, Shoban Babu; Singh, Surjit; Shukla, Ravindra; Rastogi, Ashu; Gandhi, Aravind P; Satapathy, Prakisini; Sah, Ranjit; Padhi, Bijaya Kumar; Dwivedi, Pradeep; Khunti, Kamlesh","year":2024,"journal":"Diabetes, obesity & metabolism, 26(10), 4302-4317","doi":"10.1111/dom.15777","pmid":"39044306","tags":["glp-1-receptor-agonists","weight-loss"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"GLP-1RAs vs placebo: weight -4.21 kg (CI -7.08 to -1.35), BMI -2.11 kg/m² (CI -3.60 to -0.62). Network meta-analysis ranking: semaglutide > exenatide > liraglutide > lixisenatide for weight reduction. Longer therapy duration associated with greater reductions. Consistent effects in T2DM subgroup.","whyItMatters":"Adolescent obesity is a growing crisis with limited pharmacological options. This meta-analysis provides the first head-to-head comparison of GLP-1 drugs in youth, identifying semaglutide as the most effective option and establishing that these peptide medications work in younger populations.","specificNumbers":"Searched 5 databases and registries through March 2024. Primary outcome: weight change. Pairwise and network meta-analyses performed.","methodology":"Systematic review and network meta-analysis. Five databases searched through March 2024. 12 eligible RCTs with 883 participants. Pairwise meta-analysis (GLP-1RAs vs placebo) and drug-wise NMA. Primary outcome: weight change. Secondary: BMI, waist circumference, body fat, adverse events.","limitations":"Only 12 trials with 883 participants — relatively limited evidence base. Uncertain evidence on body fat and serious adverse events. No long-term data beyond trial durations. Cost and access barriers not addressed. Network meta-analysis assumptions (transitivity, consistency) may not fully hold with heterogeneous populations."},{"rthcId":"RPEP-09245","title":"Effects of GLP-1 Receptor Agonist on Glycolipid Metabolism and Micro Inflammatory Status in Patients with Abdominal Obesity and Type 2 Diabetes.","authors":"Shao, Wei; Wu, Jianli; Zhu, Meiqin; Wang, Yanqi; Ci, Haideng","year":2024,"journal":"Alternative therapies in health and medicine","doi":null,"pmid":"38940809","tags":["liraglutide","diabetes","inflammation","weight-loss"],"studyType":"RCT","evidenceStrength":"moderate","keyFinding":"Liraglutide added to metformin significantly improved SBP, DBP, BMI, waist-hip ratio, glycolipid metabolism indices, and microinflammatory markers compared to metformin alone over 12 weeks (P<0.05). High medication safety reported.","whyItMatters":"Abdominal obesity with diabetes creates a particularly dangerous metabolic profile. Showing that liraglutide improves not just blood sugar but also inflammation — a key driver of cardiovascular risk — supports using GLP-1 peptide drugs for their broader metabolic benefits.","specificNumbers":"60 patients, 30 per group. October 2020 to December 2021 at Jiande Hospital of Traditional Chinese Medicine.","methodology":"Randomized controlled trial at a single Chinese hospital (Oct 2020-Dec 2021). 60 patients with abdominal obesity and T2D randomized to control (metformin 1g BID + lifestyle, n=30) or liraglutide group (metformin + liraglutide escalated to 1.8 mg/day, n=30) for 12 weeks.","limitations":"Small sample (30 per group). Single-center in China. 12 weeks may not capture long-term effects. Specific P-values and effect sizes for individual markers not provided in abstract. Open-label design may introduce bias."},{"rthcId":"RPEP-09246","title":"The Synthesis of SNAC Phenolate Salts and the Effect on Oral Bioavailability of Semaglutide.","authors":"Shapira-Furman, Tovi; Bar-Hai, Ayala; Hoffman, Amnon; Domb, Abraham J","year":2024,"journal":"Molecules (Basel, Switzerland), 29(16)","doi":"10.3390/molecules29163909","pmid":"39202988","tags":["semaglutide","peptide-delivery"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Three novel SNAC phenolate salts were successfully synthesized and shown to maintain equivalent oral pharmacokinetic performance for semaglutide delivery in vivo.","whyItMatters":"Oral delivery is a major challenge for peptide drugs, and SNAC is one of only a few proven absorption enhancers. Expanding the range of SNAC-based enhancers could lead to better formulations with improved stability, absorption, or patient tolerability.","specificNumbers":"Three SNAC salt forms synthesized: SNAC-choline, SNAC-sodium, and SNAC-phosphatidylcholine.","methodology":"Chemical synthesis of SNAC phenolate salts confirmed via 1H-NMR, FTIR, and elemental analysis. In vivo oral pharmacokinetic testing in rats comparing new salts to standard SNAC for semaglutide delivery.","limitations":"Only tested in rats, so human pharmacokinetics may differ. The study demonstrated non-inferiority to standard SNAC but did not show clear superiority. Long-term safety of the new salt forms was not assessed."},{"rthcId":"RPEP-09247","title":"The Role of Neuropeptide Y in the Pathogenesis of Alzheimer's Disease: Diagnostic Significance and Neuroprotective Functions.","authors":"Shapovalova, Ksenia; Zorkina, Yana; Abramova, Olga; Andryushchenko, Alisa; Chekhonin, Vladimir; Kostyuk, Georgy","year":2024,"journal":"Neurology international, 16(6), 1318-1331","doi":"10.3390/neurolint16060100","pmid":"39585059","tags":["neuroprotection","hormonal-peptides"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"NPY levels are reduced in cerebrospinal fluid and plasma of Alzheimer's patients, and NPY demonstrates neuroprotective properties in both in vitro and in vivo AD models.","whyItMatters":"Early detection of Alzheimer's disease remains a major clinical challenge, and current treatments have limited effectiveness. If NPY can reliably indicate early AD and also protect neurons, it could serve a dual role as both a diagnostic tool and a basis for new therapies.","specificNumbers":"NPY is a 36-amino-acid peptide. AD is one of the most common neurodegenerative diseases.","methodology":"Systematic review of 19 published studies identified through keyword searches for 'Alzheimer's disease and neuropeptide Y' and related terms across scientific databases.","limitations":"Many of the reviewed studies are older and used small sample sizes. Results on NPY levels in AD patients were not entirely consistent (some showed reductions, others no change). Most neuroprotective evidence comes from animal models and cell studies, not human clinical trials."},{"rthcId":"RPEP-09248","title":"Peptide-triggered IL-12 and IFN-γ mediated immune response in CD4+ T-cells against Leishmania donovani infection.","authors":"Sharma, Swati; Anand, Anshul; Singh, Rajan; Singh, Rakesh K; Verma, Sandeep","year":2024,"journal":"Chemical communications (Cambridge, England), 60(30), 4092-4095","doi":"10.1039/d3cc05946d","pmid":"38511970","tags":["cell-penetrating-peptides","antimicrobial-peptides"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Novel tripeptides triggered pro-inflammatory IL-12 and IFN-γ secretion from CD4+CD44+ T-cells in response to Leishmania donovani, promoting a protective TH1 immune response.","whyItMatters":"Visceral leishmaniasis kills tens of thousands annually and current treatments are toxic and increasingly ineffective due to drug resistance. Peptide-based immunotherapy could offer a safer, resistance-proof alternative by harnessing the body's own immune system.","specificNumbers":"Tripeptides triggered IL-12 and IFN-γ from CD4+CD44+ T-cells.","methodology":"In vitro study using designed tripeptides combining cell-penetrating and host defense peptide properties. Measured cytokine secretion (IL-12, IFN-γ) from CD4+CD44+ T-cells exposed to Leishmania donovani antigens.","limitations":"Only tested in vitro — no animal or human studies yet. The durability and specificity of the immune response is unknown. Manufacturing and delivery challenges for clinical use were not addressed."},{"rthcId":"RPEP-09249","title":"Reactivity of N terminal histidine of peptides towards excipients/impurity of excipients: A case study of liraglutide excipient compatibility study.","authors":"Sheikh, Azahar R; Vitore, Jyotsna G; Bhalekar, Vijay S; Jain, Sonali; Kukreja, Divya; Giri, Tushar; Sharma, Nitish; Benival, Derajram; Shah, Ravi P","year":2024,"journal":"Journal of pharmaceutical sciences, 113(11), 3246-3254","doi":"10.1016/j.xphs.2024.08.007","pmid":"39179028","tags":["liraglutide","peptide-engineering","peptide-safety"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"N-terminal histidine of liraglutide reacts with formaldehyde impurities in excipients and PLGA degradation products, forming imidazopyrimidine, glycolyl, and lactolyl interaction products.","whyItMatters":"Peptide drug stability is critical for patient safety and drug efficacy. If excipient impurities silently modify the active peptide, it could reduce potency or create potentially immunogenic degradation products. This study highlights a previously underappreciated source of instability.","specificNumbers":"Formaldehyde reported as impurity in PEG, glycerol, magnesium stearate, microcrystalline cellulose, and mannitol.","methodology":"Excipient compatibility study using LC-HRMS, MS/MS, and hydrogen-deuterium exchange mass spectrometry to identify and characterize peptide-excipient interaction products during liraglutide formulation development.","limitations":"Focused solely on liraglutide and its specific excipient combinations. The clinical significance of the interaction products (e.g., whether they affect efficacy or safety) was not evaluated. Did not assess whether these interactions occur at levels that would affect commercial products."},{"rthcId":"RPEP-09250","title":"GLP-1 receptor agonist attenuates tubular cell ferroptosis in diabetes via enhancing AMPK-fatty acid metabolism pathway through macropinocytosis.","authors":"Shen, Rui; Qin, Songyan; Lv, Yunhui; Liu, Dandan; Ke, Qingqing; Shi, Caifeng; Jiang, Lei; Yang, Junwei; Zhou, Yang","year":2024,"journal":"Biochimica et biophysica acta. Molecular basis of disease, 1870(4), 167060","doi":"10.1016/j.bbadis.2024.167060","pmid":"38354757","tags":["glp-1-receptor-agonists","kidney","diabetes"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Exendin-4 suppressed ferroptosis in diabetic kidney tubular cells by activating AMPK-fatty acid metabolism signaling, reducing iron overload and lipid peroxidation through macropinocytosis-dependent cellular uptake.","whyItMatters":"GLP-1 receptor agonists are already known to benefit kidney outcomes in diabetes, but the mechanisms have been unclear. This study reveals a specific protective pathway — suppression of ferroptosis via AMPK — that explains how these drugs protect kidneys beyond just lowering blood sugar and weight.","specificNumbers":"Three pillars of tubular ferroptosis: iron reabsorption, lipid metabolism, and redox-active compound exposure.","methodology":"Preclinical study using diabetic kidney models (in vitro and in vivo). Examined ferroptosis markers (GPX4, GSH, ACSL4, iron levels), AMPK signaling, fatty acid oxidation, and macropinocytosis pathways.","limitations":"Preclinical study using exendin-4, not the more commonly prescribed semaglutide or liraglutide. Results from cell and animal models may not fully translate to human diabetic kidney disease. The relative contribution of ferroptosis versus other cell death pathways in human DKD is not established."},{"rthcId":"RPEP-09251","title":"Structural basis of neuropeptide Y signaling through Y1 and Y2 receptors.","authors":"Shen, Siyuan; Deng, Yue; Shen, Chenglong; Chen, Haidi; Cheng, Lin; Wu, Chao; Zhao, Chang; Yang, Zhiqian; Hou, Hanlin; Wang, Kexin; Shao, Zhenhua; Deng, Cheng; Ye, Feng; Yan, Wei","year":2024,"journal":"MedComm, 5(7), e565","doi":"10.1002/mco2.565","pmid":"38882210","tags":["hormonal-peptides","receptor-signaling"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Three cryo-EM structures of Gi2-coupled Y1R and Y2R with NPY revealed a conserved peptide-binding mode and an additional sub-pocket conferring ligand selectivity, with evidence of evolutionary adaptation in this selectivity region.","whyItMatters":"Understanding exactly how NPY binds its different receptor subtypes is crucial for designing drugs that target one receptor without affecting others. This could lead to more precise treatments for conditions like obesity, anxiety, cardiovascular disease, and cancer.","specificNumbers":"NPY is a 36-amino-acid peptide. [Pro34]-NPY and [Leu31, Pro34]-NPY mainly act on Y1R; other analogs show Y2R selectivity.","methodology":"Cryo-electron microscopy (cryo-EM) structural determination of three receptor-peptide complexes: Y1R-NPY, Y1R-[Leu31,Pro34]-NPY, and Y2R-NPY, all coupled to Gi2. Combined with cell-based functional assays and evolutionary analysis.","limitations":"Structures represent receptor complexes stabilized for cryo-EM, which may not capture all conformational states occurring in living cells. The evolutionary analysis of the sub-pocket needs functional validation across species. Clinical drug design based on these structures has not yet been attempted."},{"rthcId":"RPEP-09252","title":"The Efficacy and Safety of Liraglutide in Patients Remaining Obese 6 Months after Metabolic Surgery.","authors":"Shen, Yuanyuan; Huang, Yuanhao; Ouyang, Yuqin; Xiang, Xinyue; Chu, Xuehui; Zhang, Bingqing; Han, Tao; Tang, Wenjuan; Feng, Wenhuan","year":2024,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 15(12), 2499-2513","doi":"10.1007/s13300-024-01643-1","pmid":"39443333","tags":["liraglutide","weight-loss"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Twelve weeks of liraglutide (1.8mg) in post-bariatric patients with persistent obesity produced 11.6% total weight loss versus 4.9% in controls, with an estimated treatment difference of 6.6% and improved metabolic outcomes.","whyItMatters":"Bariatric surgery doesn't work equally for everyone, and some patients need additional help losing weight. This study provides evidence that adding liraglutide relatively early after surgery can significantly boost weight loss results, potentially preventing the long-term health consequences of persistent obesity.","specificNumbers":"61 patients with BMI ≥28.0 kg/m² at 6 months postoperatively. Liraglutide 1.8 mg used.","methodology":"Retrospective cohort study of 61 patients with BMI ≥28 kg/m² at 6 months post-metabolic surgery. 27 received liraglutide 1.8mg for 12 weeks; 34 were controls. Primary endpoint: change in %TWL at 24 weeks.","limitations":"Retrospective design limits causal conclusions. Small sample size (n=61) with unequal groups. Used the lower 1.8mg dose (the weight-management dose is 3.0mg). Short treatment period (12 weeks) with 24-week follow-up. Single-center study."},{"rthcId":"RPEP-09253","title":"Wernicke Encephalopathy Associated With Semaglutide Use.","authors":"Sheth, Krishna; Garza, Elizabeth; Saju, Ajith; Nazir, Natasha; Agarwal, Aditya","year":2024,"journal":"Cureus, 16(6), e61783","doi":"10.7759/cureus.61783","pmid":"38975533","tags":["semaglutide","peptide-safety"],"studyType":"case series","evidenceStrength":"preliminary","keyFinding":"Non-alcoholic Wernicke encephalopathy occurred in a 37-year-old male patient in the setting of semaglutide use, presenting with dysphagia, slurred speech, word-finding difficulty, and restricted extraocular movements.","whyItMatters":"As millions of people use semaglutide for weight loss and diabetes, clinicians need to be aware that severe appetite suppression can lead to dangerous nutritional deficiencies. Wernicke encephalopathy can cause permanent brain damage if not recognized and treated promptly with thiamine.","specificNumbers":"37-year-old male, non-alcoholic. Presented with dysphagia, slurred speech, and word-finding difficulties.","methodology":"Single case report documenting clinical presentation, diagnostic workup, and association with semaglutide use in a patient with non-alcoholic Wernicke encephalopathy.","limitations":"Single case report — cannot establish causation between semaglutide and Wernicke encephalopathy. Other contributing factors to malnutrition may not have been fully explored. The overall incidence of this complication with GLP-1 drugs is unknown."},{"rthcId":"RPEP-09254","title":"Liraglutide ameliorates high glucose-induced vascular endothelial injury through TRIB3/NF-κB signaling pathway.","authors":"Shi, Lili; Xu, Yingying; Zhao, Chao; Qu, Guangjin; Hao, Ming","year":2024,"journal":"In vitro cellular & developmental biology. Animal, 60(9), 1046-1057","doi":"10.1007/s11626-024-00947-7","pmid":"39039329","tags":["liraglutide","cardiovascular","diabetes"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Liraglutide protected endothelial cells from high glucose-induced apoptosis, oxidative stress, inflammasome activation, and pyroptosis by regulating the TRIB3/NF-κB/IκB-α signaling pathway.","whyItMatters":"Vascular complications are the leading cause of death in diabetes. Understanding how liraglutide protects blood vessel cells — beyond its blood sugar-lowering effects — could help explain the cardiovascular benefits seen in clinical trials and guide treatment decisions.","specificNumbers":"Human umbilical vein endothelial cell injury model with high glucose exposure.","methodology":"In vitro study using human umbilical vein endothelial cells (HUVECs) exposed to high glucose with and without liraglutide pretreatment. TRIB3 silencing experiments confirmed the mechanism. Measured apoptosis markers, ROS levels, and inflammasome components.","limitations":"In vitro study using a single cell type (HUVECs) — may not fully represent the complex vascular environment in living patients. High glucose concentrations used in lab settings may not exactly mirror physiological conditions. No animal or clinical validation."},{"rthcId":"RPEP-09255","title":"Significant elevation of serum CA19-9 and CA242 levels induced by dulaglutide.","authors":"Shi, Xiaomin","year":2024,"journal":"BMJ case reports, 17(5)","doi":"10.1136/bcr-2023-257657","pmid":"38719260","tags":["glp-1-receptor-agonists","peptide-safety","cancer"],"studyType":"case series","evidenceStrength":"preliminary","keyFinding":"Dulaglutide caused significant elevation of serum CA19-9 and CA242 levels in an asymptomatic patient, which completely normalized within 6 weeks of drug discontinuation.","whyItMatters":"As GLP-1 drugs become increasingly common, clinicians will encounter more patients with unexplained elevated tumor markers. Knowing that dulaglutide can cause this effect could prevent unnecessary invasive procedures, reduce patient anxiety, and save healthcare resources.","specificNumbers":"Mid-60s female, dulaglutide for 16 months. Elevated CA19-9 and CA242 resolved after stopping.","methodology":"Single case report with clinical workup including imaging and interventional assessments to exclude malignancy, followed by dulaglutide discontinuation and marker monitoring.","limitations":"Single case report — cannot determine how common this effect is. The mechanism by which dulaglutide elevates these markers was not investigated. It's unclear whether other GLP-1 drugs cause similar marker elevations."},{"rthcId":"RPEP-09256","title":"Real-world experience with calcitonin gene-related peptide-targeted antibodies for migraine prevention: a retrospective observational cohort study at two Japanese headache centers.","authors":"Shibata, Mamoru; Fujita, Kazuki; Hoshino, Eri; Minami, Kazushi; Koizumi, Kenzo; Okada, Satoshi; Sakai, Fumihiko","year":2024,"journal":"BMC neurology, 24(1), 32","doi":"10.1186/s12883-023-03521-y","pmid":"38238659","tags":["cgrp","migraine"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"CGRP mAbs reduced monthly migraine days from 13.4 to 7.4 (p<0.0001) with a 50% response rate, and early response after 1-2 doses predicted sustained benefit at 3 doses (OR: 3.474, p=0.047).","whyItMatters":"Real-world data confirming CGRP antibody effectiveness in Japanese patients fills an important gap, since genetic and physiological differences can affect drug response across populations. The finding that early response predicts outcomes helps clinicians decide sooner whether to continue treatment.","specificNumbers":"Three drugs evaluated: galcanezumab, fremanezumab, and erenumab at two Japanese headache centers.","methodology":"Retrospective observational cohort study at two Japanese headache centers. 68 patients who failed ≥1 oral preventive received galcanezumab, fremanezumab, or erenumab. Primary endpoints: change in monthly migraine days and HIT-6 score after 3 dosing intervals.","limitations":"Retrospective design with no control group. Relatively small sample (n=68). Single ethnicity (Japanese). Combined three different CGRP antibodies in one analysis. Short follow-up period (3 dosing intervals)."},{"rthcId":"RPEP-09257","title":"Anti-Calcitonin Gene-Related Peptide Monoclonal Antibody Is Effective for Preventing Migraine Aura Without Headache.","authors":"Shibata, Yasushi","year":2024,"journal":"Neurology international, 16(6), 1279-1284","doi":"10.3390/neurolint16060097","pmid":"39585056","tags":["cgrp","migraine"],"studyType":"case series","evidenceStrength":"preliminary","keyFinding":"Galcanezumab completely prevented migraine aura without headache within one day of first administration in a patient with a 39-year history of the condition.","whyItMatters":"Migraine aura without headache is an underrecognized condition with limited treatment options. CGRP antibodies are currently only approved for migraines with and without aura (but with headache). This case suggests they could help a group of patients who have been largely overlooked.","specificNumbers":"49-year-old female, history since age 10 (39 years). Photosensitivity and typical migraine auras without headache.","methodology":"Single case report documenting the clinical response of a 49-year-old female patient with migraine aura without headache to galcanezumab 120mg monthly.","limitations":"Single case report — cannot establish efficacy for the broader population with migraine aura without headache. The rapid onset (1 day) is unusual and may not be typical. Placebo effect cannot be ruled out without a controlled trial. Long-term outcomes not reported."},{"rthcId":"RPEP-09258","title":"Transdermal Properties of Cell-Penetrating Peptides: Applications and Skin Penetration Mechanisms.","authors":"Shin, Hee Je; Lee, Byung Kyu; Kang, Hyun Ah","year":2024,"journal":"ACS applied bio materials, 7(1), 1-16","doi":"10.1021/acsabm.3c00659","pmid":"38079575","tags":["cell-penetrating-peptides","peptide-delivery"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"CPPs penetrate skin through molecular interactions with the lipid lamellar structure between corneocytes in the stratum corneum, enabling transdermal delivery of macromolecules for therapeutic and cosmetic applications.","whyItMatters":"Many effective drugs (including peptides, proteins, and nucleic acids) cannot be taken orally and require injection. CPP-based transdermal delivery could eliminate needles for some treatments, improving patient compliance and enabling new therapeutic applications.","specificNumbers":"CPPs consist of 5-30 amino acids with intracellular transduction abilities.","methodology":"Narrative review of published literature on cell-penetrating peptide transduction mechanisms, transdermal applications, skin penetration pathways, and safety profiles.","limitations":"Review article summarizing existing research — no new experimental data. Skin penetration mechanisms are still not fully understood at the molecular level. Translation from lab studies to commercial products remains challenging. Safety of long-term CPP skin exposure needs more investigation."},{"rthcId":"RPEP-09259","title":"Efficacy and Safety of Lu-177 DOTATATE Peptide Receptor Radionuclide Therapy in Patients with Unresectable or Metastatic Neuroendocrine Tumors in Korea.","authors":"Shin, Yeokyeong; Moon, Bo Hyun; Ryoo, Baek-Yeol; Chang, Heung-Moon; Kim, Kyu-Pyo; Hong, Yong Sang; Kim, Tae Won; Ryu, Jin-Sook; Kim, Yong-Il; Yoo, Changhoon","year":2024,"journal":"Targeted oncology, 19(1), 41-49","doi":"10.1007/s11523-023-01022-z","pmid":"38108953","tags":["somatostatin","cancer","radionuclide-therapy"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Lu-177 DOTATATE PRRT in Korean NET patients achieved median PFS of 21.7 months, 20% ORR, and 88% one-year OS, with significantly better outcomes in grade 1-2 versus grade 3 tumors (HR 3.15, p=0.006).","whyItMatters":"Confirming that peptide receptor radionuclide therapy works equally well in Asian patients addresses a significant evidence gap. This gives Korean and other Asian oncologists confidence in offering this treatment and helps establish local treatment protocols.","specificNumbers":"Korean patients with advanced NETs. Lu-177 PRRT evaluated for efficacy and safety.","methodology":"Retrospective study of 64 patients treated with Lu-177 DOTATATE PRRT at Asan Medical Center, Seoul, between November 2019 and December 2022. Evaluated PFS, OS, ORR, and safety. Median follow-up: 15.7 months.","limitations":"Retrospective design without a control group. Single-center study from a major academic hospital, which may not represent all Korean treatment centers. Median OS not reached due to relatively short follow-up. Combined heterogeneous NET primary sites and grades."},{"rthcId":"RPEP-09260","title":"Exploring the association between weight loss-inducing medications and multiple sclerosis: insights from the FDA adverse event reporting system database.","authors":"Shirani, Afsaneh; Cross, Anne H; Stuve, Olaf","year":2024,"journal":"Therapeutic advances in neurological disorders, 17, 17562864241241383","doi":"10.1177/17562864241241383","pmid":"38566910","tags":["glp-1-receptor-agonists","neuroprotection","weight-loss"],"studyType":"cohort","evidenceStrength":"preliminary","keyFinding":"GLP-1 receptor agonists showed significant inverse associations with MS: semaglutide ROR 0.238, dulaglutide ROR 0.165, liraglutide ROR 0.161 (all p<0.05), while non-GLP-1 weight-loss drugs showed no inverse association.","whyItMatters":"Multiple sclerosis affects millions worldwide and current treatments are immunosuppressive with significant side effects. If GLP-1 drugs have genuine protective effects against MS, they could represent a safer, more tolerable treatment option — especially since they're already widely used and well-understood.","specificNumbers":"Analysis of FDA AERS database. Obesity linked to MS through pro-inflammatory adipokines like leptin.","methodology":"Disproportionality analysis of the FDA Adverse Event Reporting System (FAERS) database from Q4 2003 to Q2 2023. Inverse association defined as upper limit of 95% CI for reporting odds ratio <1.","limitations":"FAERS database analysis cannot establish causation — only association. Reporting biases are inherent (e.g., diabetic patients may be less likely to also have MS diagnosed, or MS patients may avoid GLP-1 drugs). Confounders like age, sex, and comorbidities could not be fully controlled."},{"rthcId":"RPEP-09261","title":"Antihypertensive peptide resources map of ribulose-1,5-bisphosphate carboxylase/oxygenases (RuBisCO) in angiosperms: Revealed by an integrated in silico and in vitro approach.","authors":"Shu, Haoyue; Zhao, Qingcui; Huang, Yu; Shi, Qiong; Yang, Jian","year":2024,"journal":"Food chemistry, 433, 137332","doi":"10.1016/j.foodchem.2023.137332","pmid":"37683466","tags":["bioactive-peptides","blood-pressure"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Three novel RuBisCO-derived peptides showed ACE-inhibitory activity: TTVW (IC50: 12.89 μM), TMW (IC50: 23.97 μM) as noncompetitive inhibitors, and VPCL (IC50: 339.12 μM) as a competitive inhibitor.","whyItMatters":"Hypertension affects over a billion people globally, and many seek dietary approaches alongside medication. Identifying potent antihypertensive peptides from the world's most abundant protein opens practical pathways for functional foods and nutraceuticals that could complement blood pressure management.","specificNumbers":"12,766 large subunit and 1,020 small subunit RuBisCO sequences from angiosperms analyzed.","methodology":"Combined in silico (simulated proteolysis of 12,766 RuBisCO large subunit and 1,020 small subunit sequences) and in vitro (ACE inhibition assays with IC50 determination and molecular docking) approach.","limitations":"In vitro ACE inhibition does not guarantee in vivo blood pressure reduction — peptides must survive digestion, be absorbed, and reach target tissues at effective concentrations. No animal or human studies conducted. IC50 values may not translate to clinical efficacy."},{"rthcId":"RPEP-09262","title":"2023 U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guideline for the Management of Headache.","authors":"Sico, Jason J; Antonovich, Natasha M; Ballard-Hernandez, Jennifer; Buelt, Andrew C; Grinberg, Amy S; Macedo, Franz J; Pace, Ian W; Reston, James; Sall, James; Sandbrink, Friedhelm; Skop, Karen M; Stark, Thomas R; Vogsland, Rebecca; Wayman, Lisa; Ford, Aven W","year":2024,"journal":"Annals of internal medicine, 177(12), 1675-1694","doi":"10.7326/ANNALS-24-00551","pmid":"39467289","tags":["cgrp","migraine"],"studyType":"review","evidenceStrength":"strong","keyFinding":"The 2023 VA/DoD guideline incorporates CGRP inhibitors (gepants for acute treatment, CGRP monoclonal antibodies and atogepant for prevention) as recommended options for migraine management alongside traditional treatments.","whyItMatters":"Military and veteran populations have high rates of headache disorders. This guideline update reflects the clinical maturation of CGRP-targeting therapies and provides evidence-based direction for millions of patients in the VA/DoD healthcare system — and influences civilian practice as well.","specificNumbers":"Revised in 2023, earlier than the standard 5-year cycle from the 2020 guideline.","methodology":"Clinical practice guideline developed by VA/DoD subject matter experts based on systematic review of 5 databases (March 2019 - August 2022), with consensus recommendations considering evidence quality, patient preferences, and benefit-harm balance.","limitations":"Evidence review ended in August 2022, so very recent CGRP data may not be reflected. Guidelines are developed for VA/DoD populations, which skew male and may have different comorbidity profiles than the general population. Implementation and access to newer CGRP drugs may vary across VA facilities."},{"rthcId":"RPEP-09263","title":"Neuroprotective effects of GLP-1 receptor agonists in neurodegenerative Disorders: A Large-Scale Propensity-Matched cohort study.","authors":"Siddeeque, Nabeela; Hussein, Mohammad H; Abdelmaksoud, Ahmed; Bishop, Julia; Attia, Abdallah S; Elshazli, Rami M; Fawzy, Manal S; Toraih, Eman A","year":2024,"journal":"International immunopharmacology, 143(Pt 3), 113537","doi":"10.1016/j.intimp.2024.113537","pmid":"39486172","tags":["glp-1-receptor-agonists","neuroprotection"],"studyType":"cohort","evidenceStrength":"strong","keyFinding":"GLP-1RAs reduced risk of Alzheimer's (RR=0.627), Lewy body dementia (RR=0.590), and vascular dementia (RR=0.438). Semaglutide specifically reduced Parkinson's risk (RR=0.574) and showed the most pronounced protective effects across all disorders.","whyItMatters":"Neurodegenerative diseases affect tens of millions worldwide with no cure. Finding that widely available drugs like semaglutide may prevent these conditions could be transformative — especially given the scale of this evidence base spanning 17 countries and millions of patients.","specificNumbers":"5,307,845 obese patients analyzed. Propensity-matched comparison of GLP-1RA users vs. non-users.","methodology":"Retrospective propensity-matched cohort study of 5,307,845 obese adults from 73 healthcare organizations in 17 countries. 102,935 patients matched per cohort. Compared neurodegenerative disease incidence between GLP-1RA users and non-users.","limitations":"Retrospective observational design cannot prove causation. Propensity matching reduces but doesn't eliminate confounding. The study population was obese, so results may not generalize to non-obese individuals. Neurodegenerative disease diagnoses in claims databases may be less accurate than in specialized research settings."},{"rthcId":"RPEP-09264","title":"Importance of glucose and its metabolism in neurodegenerative disorder, as well as the combination of multiple therapeutic strategies targeting α-synuclein and neuroprotection in the treatment of Parkinson's disease.","authors":"Siddique, A H H; Kale, P P","year":2024,"journal":"Revue neurologique, 180(8), 736-753","doi":"10.1016/j.neurol.2023.08.011","pmid":"38040547","tags":["glp-1-receptor-agonists","neuroprotection"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Combination therapies targeting energy metabolism pathways — including GLP-1 receptor agonists, PGK-1 enhancers, and A2A receptor modulators — may offer synergistic neuroprotection for Parkinson's disease.","whyItMatters":"Current Parkinson's treatments only manage symptoms — none slow disease progression. If energy metabolism pathways can be therapeutically targeted, especially using drugs like exenatide that already have clinical safety data, this could lead to disease-modifying treatments.","specificNumbers":"PGK-1 enzyme mutations linked to Parkinson's. Energy deficit from reduced glycolytic ATP production.","methodology":"Narrative review of published literature on PGK-1 enzyme mutations, GLP-1 receptor agonist neuroprotection, and A2A receptor involvement in Parkinson's disease pathogenesis and treatment.","limitations":"Narrative review without systematic methodology. Proposed combinations are theoretical and have not been tested together in clinical trials. The mechanistic links between PGK-1, GLP-1, and A2A pathways in PD need more experimental validation."},{"rthcId":"RPEP-09265","title":"Approved and Emerging Hormone-Based Anti-Obesity Medications: A Review Article.","authors":"Sidrak, Wael R; Kalra, Sanjay; Kalhan, Atul","year":2024,"journal":"Indian journal of endocrinology and metabolism, 28(5), 445-460","doi":"10.4103/ijem.ijem_442_23","pmid":"39676791","tags":["glp-1-receptor-agonists","semaglutide","tirzepatide","weight-loss"],"studyType":"review","evidenceStrength":"strong","keyFinding":"The evolution from single-target GLP-1 drugs to dual and triple receptor agonists is producing dramatically greater weight loss: tirzepatide (GIP/GLP-1) achieves 17.8% and retatrutide (GLP-1/GCG/GIP tri-agonist) achieves 22.1% placebo-subtracted weight reduction.","whyItMatters":"Obesity affects over a billion people globally. The rapid advancement from single-target to multi-target hormone therapies is producing progressively greater weight loss, potentially approaching the efficacy of bariatric surgery with a medication-only approach.","specificNumbers":"Two GLP-1RAs are frontrunners. Triple agonists like retatrutide represent the next wave.","methodology":"Narrative review of approved and emerging hormone-based anti-obesity medications, covering published clinical trial data for GLP-1RAs, dual and triple agonists, and amylin receptor agonists.","limitations":"Review article — no new data generated. Long-term safety data for newer agents (tirzepatide, retatrutide) is limited. Cardiovascular outcome data is available primarily for semaglutide. Cost and access remain significant barriers to widespread use."},{"rthcId":"RPEP-09266","title":"The cycle effect quantified: reduced tumour uptake in subsequent cycles of [177Lu]Lu-HA-DOTATATE during peptide receptor radionuclide therapy.","authors":"Siebinga, H; Hendrikx, J J M A; de Vries-Huizing, D M V; Huitema, A D R; de Wit-van der Veen, B J","year":2024,"journal":"European journal of nuclear medicine and molecular imaging, 51(3), 820-827","doi":"10.1007/s00259-023-06463-2","pmid":"37843598","tags":["somatostatin","cancer","radionuclide-therapy"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Tumor uptake of Lu-177 DOTATATE decreased progressively: 86.9% (cycle 2), 79.7% (cycle 3), and 77.6% (cycle 4) of first-cycle levels. The plateau pattern suggests receptor downregulation is likely not the primary cause.","whyItMatters":"Understanding why tumors absorb less radiation over treatment cycles is critical for optimizing PRRT dosing. If clinicians know the expected reduction, they may adjust doses, combine therapies, or time cycles differently to maximize treatment effectiveness.","specificNumbers":"48 patients with multiple PRRT cycles. Five-compartment pharmacokinetic model used.","methodology":"Population pharmacokinetic model using imaging data from 48 patients receiving multiple Lu-177 HA-DOTATATE cycles. Five-compartment model (central, kidney, spleen, tumor, rest). Evaluated tumor volume and SSA use as covariates.","limitations":"Retrospective modeling from a single center. Used imaging-derived uptake data which has inherent measurement variability. The study used Lu-177 HA-DOTATATE (a specific formulation), and results may not perfectly transfer to other DOTATATE preparations. The cause of the cycle effect remains uncertain."},{"rthcId":"RPEP-09267","title":"Evaluating delivery of peptide nucleic acids to Gram-negative bacteria using differently linked membrane-active peptides and their stapled analogs.","authors":"Siekierska, Izabela; Burmistrz, Michał; Trylska, Joanna","year":2024,"journal":"Bioorganic & medicinal chemistry letters, 114, 129993","doi":"10.1016/j.bmcl.2024.129993","pmid":"39426432","tags":["antimicrobial-peptides","cell-penetrating-peptides"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Anoplin conjugated to PNA via a non-cleavable ethylene glycol linker demonstrated antibacterial activity against E. coli and S. Typhimurium at 2-4 μM, establishing it as an effective new PNA carrier peptide.","whyItMatters":"Antibiotic resistance is a global health crisis. Antisense PNA technology can target genes that are essential for bacterial survival, but delivery into Gram-negative bacteria has been a major bottleneck. Identifying effective carrier peptides like anoplin brings this technology closer to clinical application.","specificNumbers":"Multiple linker types and stapled analogs tested against Gram-negative bacteria.","methodology":"In vitro study testing peptide-PNA conjugates with different carrier peptides (anoplin, (KFF)₃K, and their stapled analogs) and linkers (non-cleavable eg1 vs. reducible disulfide) against various Gram-negative bacterial strains. PNA targeted acyl carrier protein mRNA.","limitations":"In vitro testing only — no animal infection models. Limited to two Gram-negative species. The mechanism by which anoplin delivers PNA while stapled peptides fail is not fully explained. Cytotoxicity to human cells was not comprehensively assessed."},{"rthcId":"RPEP-09268","title":"New studies with stable gastric pentadecapeptide protecting gastrointestinal tract. significance of counteraction of vascular and multiorgan failure of occlusion/occlusion-like syndrome in cytoprotection/organoprotection.","authors":"Sikiric, Predrag; Sever, Marko; Krezic, Ivan; Vranes, Hrvoje; Kalogjera, Luka; Smoday, Ivan Maria; Vukovic, Vlasta; Oroz, Katarina; Coric, Luka; Skoro, Marija; Kavelj, Ivana; Zubcic, Slavica; Sikiric, Suncana; Beketic Oreskovic, Lidija; Oreskovic, Ivana; Blagaic, Vladimir; Brcic, Klara; Strbe, Sanja; Staresinic, Mario; Boban Blagaic, Alenka; Skrtic, Anita; Seiwerth, Sven","year":2024,"journal":"Inflammopharmacology, 32(5), 3119-3161","doi":"10.1007/s10787-024-01499-8","pmid":"38980576","tags":["bpc-157","gut-health","organ-protection","vascular-health"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"BPC 157 counteracts advanced vascular occlusion syndromes by activating collateral rescuing pathways including azygos vein direct blood flow delivery, protecting multiple organs from ischemic damage across diverse experimental models.","whyItMatters":"Vascular occlusion underlies many medical emergencies (heart attack, stroke, organ ischemia). If BPC 157 can truly activate collateral blood flow pathways, it could represent a novel approach to protecting organs during vascular crises — though clinical evidence remains limited.","specificNumbers":"The review spans research from the early 1990s to 2024, covering studies across multiple organ systems in animal models.","methodology":"Comprehensive narrative review of published BPC 157 research, covering cytoprotection mechanisms, vascular recovery, collateral pathway activation, and multi-organ protection in occlusion/occlusion-like syndromes.","limitations":"Most evidence comes from animal models. Clinical data is limited to one phase II trial in ulcerative colitis. The claimed breadth of effects across nearly every organ system raises skepticism about mechanism specificity. Many studies come from a single research group, which limits independent validation."},{"rthcId":"RPEP-09269","title":"Gastrointestinal delivery of codfish Skin-Derived collagen Hydrolysates: Deep eutectic solvent extraction and bioactivity analysis.","authors":"Silva, Isa; Vaz, Bárbara M C; Sousa, Sérgio; Pintado, Maria Manuela; Coscueta, Ezequiel R; Ventura, Sónia P M","year":2024,"journal":"Food research international (Ottawa, Ont.), 175, 113729","doi":"10.1016/j.foodres.2023.113729","pmid":"38128988","tags":["collagen-peptides","antioxidant-effects","bioavailability"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Codfish skin collagen hydrolysates achieved 961 µmol TE antioxidant activity and 39.3% ACE inhibition. Chitosan-TPP encapsulation enabled 58% intestinal release in a simulated GI tract model.","whyItMatters":"Valorizing fish industry waste into health-promoting peptides addresses both sustainability and health goals. The combination of green extraction, demonstrated bioactivity, and targeted gut delivery brings this closer to a viable nutraceutical product.","specificNumbers":"The extraction yielded 2.2% collagen. Antioxidant activity measured at 961 µmol TE. Enzymatic hydrolysis ran for 120 minutes.","methodology":"In vitro study: collagen extracted from codfish skin using urea:propanoic acid (1:2) deep eutectic solvent (2.2% yield). Enzymatic hydrolysis with alcalase (120 min). Bioactivity assays for antioxidant and ACE inhibition. Encapsulation in chitosan-TPP capsules with simulated GI digestion testing.","limitations":"In vitro study only — no human subjects. ACE inhibition of 39.3% is moderate and may not translate to clinically meaningful blood pressure reduction in vivo. The simulated GI model is simplified compared to real digestion. Long-term stability of the encapsulated peptides was not assessed."},{"rthcId":"RPEP-09270","title":"Lineage-tracing reveals an expanded population of NPY neurons in the inferior colliculus.","authors":"Silveira, Marina A; Herrera, Yoani N; Beebe, Nichole L; Schofield, Brett R; Roberts, Michael T","year":2024,"journal":"Journal of neurophysiology, 132(2), 573-588","doi":"10.1152/jn.00131.2024","pmid":"38988288","tags":["neuropeptides","brain-and-cognition"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Lineage-tracing revealed a larger population of NPY neurons in the inferior colliculus than expression-tracking alone, and optogenetic experiments confirmed these neurons form local inhibitory synaptic circuits.","whyItMatters":"Understanding how neuropeptides modulate auditory circuits is fundamental to hearing science. The finding that NPY expression is dynamic — and that the NPY neuron population is larger than thought — changes our understanding of neuropeptide regulation in the auditory system and may have implications for conditions like tinnitus and hyperacusis.","specificNumbers":"The lineage-tracing method revealed significantly more NPY-expressing neurons than the standard reporter mouse approach across multiple regions of the inferior colliculus.","methodology":"Mouse study comparing expression-tracking (NPY-hrGFP) and lineage-tracing approaches to quantify NPY neuron populations in the inferior colliculus. Optogenetic stimulation tested local connectivity of NPY neurons. Physiological and anatomical features characterized.","limitations":"Mouse study — findings may not directly translate to human auditory processing. The functional consequences of dynamic NPY regulation (what triggers expression changes) were not determined. The study focused on the IC; other auditory regions were not examined."},{"rthcId":"RPEP-09271","title":"Glucagon-like peptide-1 receptor agonists and risk of thyroid cancer: A systematic review and meta-analysis of randomized controlled trials.","authors":"Silverii, Giovanni Antonio; Monami, Matteo; Gallo, Marco; Ragni, Alberto; Prattichizzo, Francesco; Renzelli, Valerio; Ceriello, Antonio; Mannucci, Edoardo","year":2024,"journal":"Diabetes, obesity & metabolism, 26(3), 891-900","doi":"10.1111/dom.15382","pmid":"38018310","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 64 randomized controlled trials, GLP-1 receptor agonist treatment was associated with a statistically significant increase in overall thyroid cancer risk, with a Mantel-Haenszel odds ratio of 1.52 (95% CI: 1.01–2.29, p=0.04). There was no significant heterogeneity between studies (I²=0%).\n\nThe fragility index was just 1, meaning a single event change would eliminate statistical significance. The 5-year number needed to harm was 1,349 — meaning approximately 1 extra thyroid cancer case per 1,349 patients treated for 5 years.\n\nWhen restricted to trials lasting at least 104 weeks, the association strengthened slightly (OR 1.76, 95% CI: 1.00–3.12). However, neither papillary thyroid cancer (OR 1.54, p=0.22) nor medullary thyroid cancer (OR 1.44, p=0.55) reached significance individually.","whyItMatters":"With tens of millions of people now taking GLP-1 drugs like Ozempic and Mounjaro, even a small increase in cancer risk has enormous public health implications. Rodent studies had previously shown thyroid tumors with GLP-1 drugs, but human data has been unclear. This is one of the largest meta-analyses to specifically examine thyroid cancer risk with GLP-1 receptor agonists using only randomized trial data — the gold standard for causality assessment.","specificNumbers":"","methodology":"This was a systematic review and meta-analysis of randomized controlled trials comparing any GLP-1 receptor agonist to any comparator. Included trials had to last at least 52 weeks and report adverse event incidence. Researchers collected all thyroid cancer cases across 64 eligible trials and calculated pooled odds ratios using the Mantel-Haenszel method. They also performed subgroup analyses by cancer subtype and trial duration.","limitations":"The fragility index of 1 means the overall finding is statistically fragile — a single event change would make it non-significant. Most trials were designed to study diabetes or weight loss, not cancer, so thyroid cancer detection may have been inconsistent across studies. The longest trials were still relatively short for cancer development, and the subtype-specific analyses (papillary, medullary) were underpowered. The meta-analysis cannot determine whether specific GLP-1 drugs carry more or less risk than others."},{"rthcId":"RPEP-09272","title":"Microglia Involvement into Acute and Chronic Brain Damage in Diabetic Rats: Impact of GLP-1RA and SGLT-2i.","authors":"Simanenkova, Anna; Fuks, Oksana; Timkina, Natalya; Islamova, Alina; Sufieva, Dina; Kirik, Оlga; Korzhevskii, Dmitrii; Vlasov, Timur; Karonova, Tatiana","year":2024,"journal":"Frontiers in bioscience (Landmark edition), 29(7), 265","doi":"10.31083/j.fbl2907265","pmid":"39082364","tags":["glp-1-receptor-agonists","brain-and-cognition","neuroprotection"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Liraglutide achieved the smallest brain infarcts (2.9% vs 6.2% canagliflozin, vs 17.5% untreated DM). Both GLP-1RAs reduced hippocampal microglial activation while canagliflozin did not, indicating a unique anti-neuroinflammatory mechanism for GLP-1 drugs.","whyItMatters":"Diabetic patients face doubled stroke risk and worse outcomes. Knowing which diabetes drugs also protect the brain helps clinicians choose treatments that address both metabolic and neurological risks. This direct comparison provides head-to-head evidence favoring GLP-1 drugs for neuroprotection.","specificNumbers":"Multiple drug comparisons were made between short-acting and long-acting GLP-1RAs versus SGLT2 inhibitors in diabetic rats with and without stroke.","methodology":"Rat study using high-fat diet + nicotinamide/streptozotocin diabetes model. 5 groups (n=15 each): untreated DM, liraglutide, dulaglutide, canagliflozin, and non-DM control. After 8 weeks, 10/group underwent middle cerebral artery occlusion for stroke modeling. Assessed infarct volume, neurological deficit, neurofilament light chains, S100BB, microglial activation (Iba-1), and neuronal survival.","limitations":"Rat model — metabolic and neurological responses may differ from humans. Small sample sizes per group. The streptozotocin/high-fat diet model imperfectly replicates human type 2 diabetes. Drug doses may not directly translate to human equivalent doses. Short treatment duration (8 weeks)."},{"rthcId":"RPEP-09273","title":"Newer glucose-lowering drugs reduce the risk of late-onset seizure and epilepsy: A meta-analysis.","authors":"Sindhu, Udeept; Sharma, Akshay; Zawar, Ifrah; Punia, Vineet","year":2024,"journal":"Epilepsia open, 9(6), 2528-2536","doi":"10.1002/epi4.13091","pmid":"39487832","tags":["glp-1-receptor-agonists","brain-and-cognition","clinical-trials"],"studyType":"meta-analysis","evidenceStrength":"moderate","keyFinding":"GLP-1 receptor agonists reduced the risk of late-onset seizures and epilepsy by 24% (RR: 0.76, 95% CI: 0.62-0.95) in a meta-analysis of 27 RCTs with ~200,000 patients. The benefit was specific to GLP-1 RAs, not DPP-4i or SGLT2i.","whyItMatters":"Late-onset epilepsy is a growing concern in aging populations. Finding that widely prescribed GLP-1 drugs also protect against seizures could be clinically significant for millions of diabetic patients, and raises the possibility of repurposing these drugs for epilepsy prevention in high-risk groups.","specificNumbers":"The analysis included data from RCTs of DPP-4 inhibitors, GLP-1 receptor agonists, and SGLT2 inhibitors across multiple databases (MEDLINE and CENTRAL).","methodology":"Meta-analysis of 27 randomized controlled trials from MEDLINE and CENTRAL databases comparing newer glucose-lowering drugs (DPP-4i, GLP-1 RAs, SGLT2i) to placebo. Assessed seizure and epilepsy as adverse events. Calculated RR using Mantel-Haenszel method and OR using Peto's method. Mean age 64.9 years, 65.6% male.","limitations":"Seizures and epilepsy were captured as adverse events in cardiovascular/renal outcome trials, not as primary endpoints — potentially underreported. The mechanism (anti-inflammatory, neuroprotective, or other) is not established. The patient population was primarily older adults with type 2 diabetes — generalizability to non-diabetic populations is unknown."},{"rthcId":"RPEP-09274","title":"Contemporary Management of Obesity: A Comparison of Bariatric Metabolic Surgery and Novel Incretin Mimetic Drugs.","authors":"Singh, Abhayjit; Nissen, Steven E","year":2024,"journal":"Diabetes technology & therapeutics, 26(9), 673-685","doi":"10.1089/dia.2024.0122","pmid":"38669473","tags":["glp-1-receptor-agonists","semaglutide","weight-management"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Contemporary GLP-1-based medications and bariatric surgery are both effective for obesity management, with multiple FDA-approved GLP-1RAs and one GLP-1/GIP dual agonist now available alongside refined surgical techniques.","whyItMatters":"Clinicians and patients need clear comparisons to make informed treatment decisions. As GLP-1 drugs become more effective and bariatric surgery becomes safer, understanding the relative benefits and limitations of each approach is essential for personalized obesity care.","specificNumbers":"The review covers data on multiple drug types and surgical procedures, noting obesity has reached pandemic proportions globally over the past 50 years.","methodology":"Narrative review comparing clinical trial data and outcomes for pharmacologic (GLP-1RAs, tirzepatide) and surgical (contemporary bariatric procedures) approaches to obesity management.","limitations":"Narrative review — no systematic methodology. Head-to-head trials directly comparing GLP-1 drugs to bariatric surgery are limited. Long-term outcomes (>5 years) for newer GLP-1 drugs are not yet available. Cost and access differ significantly between approaches."},{"rthcId":"RPEP-09275","title":"GLP-1, GIP/GLP-1, and GCGR/GLP-1 receptor agonists: Novel therapeutic agents for metabolic dysfunction-associated steatohepatitis.","authors":"Singh, Anmol; Sohal, Aalam; Batta, Akash","year":2024,"journal":"World journal of gastroenterology, 30(48), 5205-5211","doi":"10.3748/wjg.v30.i48.5205","pmid":"39735270","tags":["glp-1-receptor-agonists","liver-health","metabolic-health"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Dual receptor agonists tirzepatide (GIP/GLP-1) and survodutide (GCG/GLP-1) demonstrate higher rates of MASH resolution and fibrosis improvement compared to single GLP-1 agonists alone.","whyItMatters":"MASLD affects 32.4% of the global population and has very few approved treatments. Fibrosis progression is the strongest predictor of liver-related death. Finding drugs that improve fibrosis — not just inflammation — is critical for reducing the burden of liver disease.","specificNumbers":"Global prevalence of MASLD is estimated at 32.4%. The disease is linked to increased cardiovascular, metabolic, and cancer risk.","methodology":"Narrative review of clinical trial data for GLP-1 RAs, GIP/GLP-1 dual agonists, and GCG/GLP-1 dual agonists in the treatment of MASLD/MASH.","limitations":"Review article without systematic methodology. Clinical trials of dual agonists for MASH are still in relatively early stages. Gastrointestinal tolerability remains a significant concern. Long-term hepatic outcomes are not yet established for any of these agents."},{"rthcId":"RPEP-09276","title":"Rebalancing the Gut: Glucagon-Like Peptide-1 Agonists as a Strategy for Obesity and Metabolic Health.","authors":"Singh, Kanwarmandeep; Aulakh, Smriti K; Nijjar, Gurkamal Singh; Singh, Sumerjit; Sandhu, Ajay Pal Singh; Luthra, Shivansh; Tanvir, Fnu; Kaur, Yasmeen; Singla, Abhinandan; Kaur, Meet Sirjana","year":2024,"journal":"Cureus, 16(7), e64738","doi":"10.7759/cureus.64738","pmid":"39156410","tags":["glp-1-receptor-agonists","gut-health","weight-management"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"GLP-1 agonists promote beneficial gut bacteria, enhance gut barrier integrity, reduce systemic inflammation, and increase short-chain fatty acid production, collectively disrupting the obesity-dysbiosis-inflammation cycle.","whyItMatters":"The gut microbiome is increasingly recognized as a key player in obesity and metabolic health. Understanding that GLP-1 drugs don't just suppress appetite but also improve gut health provides a more complete picture of how these medications work and may lead to optimized treatment strategies.","specificNumbers":"Specific beneficial bacteria promoted include Bacteroides, Lactobacillus, and Bifidobacterium species.","methodology":"Narrative review of published literature on the interactions between obesity, gut microbiota composition, and GLP-1 receptor agonist effects on the microbiome.","limitations":"Narrative review — no systematic search methodology. Most evidence on GLP-1 microbiome effects comes from animal studies. Human microbiome data is limited. Whether microbiome changes are a direct drug effect or secondary to weight loss and dietary changes is unclear."},{"rthcId":"RPEP-09277","title":"Cocaine- and Amphetamine-Regulated Transcript Peptide in the Central Nervous System of the Gecko, Hemidactylus leschenaultii: Molecular Characterization, Neuroanatomical Organization, and Regulation by Neuropeptide Y.","authors":"Singh, Omprakash; Basu, Sumela; Srivastava, Abhinav; Pradhan, Dipti R; Dandapat, Pallabi; Bathrachalam, Chandramohan; Singru, Praful S","year":2024,"journal":"The Journal of comparative neurology, 532(10), e25672","doi":"10.1002/cne.25672","pmid":"39380327","tags":["neuropeptides","appetite-and-metabolism","brain-and-cognition"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"CART neuropeptide was characterized for the first time in a reptilian brain (gecko), showing >93% similarity to mammalian CART peptides and regulation by NPY via Y1 receptors in the hypothalamic arcuate nucleus.","whyItMatters":"Understanding that CART-NPY interactions controlling energy balance are conserved across all vertebrate groups — from fish to reptiles to mammals — strengthens the evidence that this is a fundamental biological mechanism. This evolutionary perspective can inform therapeutic targeting of appetite-regulating peptide systems.","specificNumbers":"The gecko CART cDNA was 683 base pairs. CART-containing neurons were found across multiple brain regions.","methodology":"Cloned gecko CART cDNA (683 bp). Mapped CART-containing neurons using immunohistochemistry. Used double immunofluorescence to show NPY innervation of CART neurons. Ex vivo hypothalamic slice treatment with NPY and Y1 agonist to test regulation of CART expression.","limitations":"Single species (gecko) studied. Ex vivo hypothalamic slice experiments may not fully replicate in vivo conditions. The functional consequences of NPY-mediated CART suppression on feeding behavior in geckos were not directly measured. The ventral arcuate CART population was unaffected by NPY, and this differential regulation needs explanation."},{"rthcId":"RPEP-09278","title":"Single-Administration Self-Boosting Microneedle Patch for The Treatment of Obesity.","authors":"Singh, Parbeen; Vinikoor, Tra; Sharma, Nidhi; Nelson, Nicole; Prasadh, Somasundaram; Oiknine, Ralph; Nguyen, Thanh Duc","year":2024,"journal":"Advanced therapeutics, 7(9)","doi":"10.1002/adtp.202400028","pmid":"39429250","tags":["glp-1-receptor-agonists","semaglutide","drug-delivery"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"A single-application microneedle patch with 4 programmable core-shell pixels achieves sequential weekly semaglutide release over one month, simulating 4 separate bolus injections from one painless skin application.","whyItMatters":"Needle phobia and injection burden are major barriers to GLP-1 drug adherence. A painless, single-application monthly patch could dramatically improve patient compliance and make obesity treatment more accessible, while also reducing medical waste and the need for healthcare facilities.","specificNumbers":"Semaglutide has a half-life of approximately 7 days. The patch system delivers multiple programmed doses from a single application.","methodology":"Preclinical development of a programmable scheduled release microneedle (PSR-MN) system. Each 2cm × 2cm patch contains 4 pixel units (1cm² each) with core-shell architecture enabling time-programmed drug release at 7-day intervals.","limitations":"Preclinical stage — no human trials reported. The precise release kinetics in human skin may differ from lab testing. Scalability and manufacturing costs are not addressed. Skin reactions to the patch over a month of wear are not characterized. Storage stability of the patch needs validation."},{"rthcId":"RPEP-09279","title":"Identification of novel signal of Raynaud's phenomenon with Calcitonin Gene-Related Peptide(CGRP) antagonists using data mining algorithms and network pharmacological approaches.","authors":"Singh, Rima; Kumar, Anoop; Lather, Viney; Sharma, Ruchika; Pandita, Deepti","year":2024,"journal":"Expert opinion on drug safety, 23(2), 231-238","doi":"10.1080/14740338.2023.2248877","pmid":"37594041","tags":["cgrp","safety-and-side-effects","vascular-health"],"studyType":"cohort","evidenceStrength":"preliminary","keyFinding":"Raynaud's phenomenon was identified as a novel safety signal for all CGRP antagonists using FAERS data mining (PRR ≥2, chi-square ≥4, ROR lower 95% CI >2), with IGF1R pathway involvement suggested by network pharmacology.","whyItMatters":"CGRP is a powerful vasodilator, so blocking it could theoretically constrict blood vessels. This signal confirms that concern. Patients with pre-existing Raynaud's or vascular conditions should be monitored when starting CGRP antagonists for migraine.","specificNumbers":"Data covered reports from 2004 Q1 to 2022 Q3 in the US FAERS database.","methodology":"Data mining of FDA FAERS database (2004 Q1 - 2022 Q3) using reporting odds ratio and proportional reporting ratio algorithms. Network pharmacology using Cytoscape 3.7.2 and molecular docking with Glide (Schrödinger) to explore mechanistic pathways.","limitations":"FAERS data mining identifies signals but cannot establish causation. Reporting bias is inherent in adverse event databases. The IGF1R pathway involvement is computational prediction, not experimentally validated. The actual incidence of Raynaud's with CGRP drugs cannot be determined from this analysis."},{"rthcId":"RPEP-09280","title":"Female-selective mechanisms promoting migraine.","authors":"Singh, Shagun; Kopruszinski, Caroline M; Watanabe, Moe; Dodick, David W; Navratilova, Edita; Porreca, Frank","year":2024,"journal":"The journal of headache and pain, 25(1), 63","doi":"10.1186/s10194-024-01771-w","pmid":"38658853","tags":["cgrp","hormones-and-signaling","pain"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Prolactin produces female-selective sensory neuron sensitization and enhanced CGRP release across species (mice, primates, humans), and clinical data indicate CGRP-receptor antagonists may be preferentially effective in women for acute migraine.","whyItMatters":"Migraine affects 3x more women than men, yet treatments are rarely sex-stratified. Understanding that female-specific hormonal pathways drive migraine through CGRP could lead to more effective, personalized treatment strategies and better clinical trial design.","specificNumbers":"Migraine is approximately 3 times more common in women than men. Prolactin circulates at higher levels in females.","methodology":"Narrative review integrating preclinical data (mouse, non-human primate, human tissue studies), post-mortem analyses, and publicly available clinical trial data on sex differences in CGRP antagonist efficacy.","limitations":"Much of the evidence is preclinical. The clinical data suggesting sex differences in gepant efficacy comes from publicly available datasets, not prospective sex-stratified trials. The degree to which prolactin-CGRP interactions drive migraine in clinical practice is not fully quantified."},{"rthcId":"RPEP-09281","title":"Tumor-homing peptide iRGD-conjugate enhances tumor accumulation of camptothecin for colon cancer therapy.","authors":"Singh, Tejinder; Kim, Tae Wan; Murthy, Akula S N; Paul, Mohuya; Sepay, Nasim; Jeong Kong, Hye; Sung Ryu, Jae; Rim Koo, Na; Yoon, Sujeong; Song, Keon-Hyoung; Jun Baek, Moo; Jeon, Seob; Im, Jungkyun","year":2024,"journal":"European journal of medicinal chemistry, 265, 116050","doi":"10.1016/j.ejmech.2023.116050","pmid":"38128233","tags":["peptide-drug-conjugates","cancer-therapy","drug-delivery"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"iRGD-camptothecin conjugate showed superior cell penetration, greater colon cancer cell killing at micromolar concentrations, higher tumor accumulation, and enhanced antitumor effects compared to unconjugated camptothecin in both in vitro and in vivo models.","whyItMatters":"Camptothecin is a potent anticancer agent but suffers from poor tumor penetration and off-target toxicity. Using iRGD peptide for targeted delivery could improve the therapeutic index, delivering more drug to tumors while reducing systemic side effects.","specificNumbers":"The conjugate was linked via a heterobifunctional linker. Both in vitro and in vivo studies showed improved tumor targeting.","methodology":"In vitro: synthesized iRGD-CPT conjugate with heterobifunctional linker, tested penetration and viability in human colon cancer cells. In vivo: evaluated tumor distribution and antitumor efficacy in a mouse colon cancer model.","limitations":"Single cancer type (colon cancer) tested. Mouse xenograft models don't fully replicate human tumor biology. The stability and pharmacokinetics of the conjugate in humans are unknown. Comparison was only to free drug, not to other targeting strategies."},{"rthcId":"RPEP-09282","title":"Forecasting Trial Milestones: A Predictive Analysis for Early Termination of the SOUL Study.","authors":"Sinha, Binayak; Ghosal, Samit","year":2024,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 15(10), 2199-2209","doi":"10.1007/s13300-024-01635-1","pmid":"39115619","tags":["glp-1-receptor-agonists","semaglutide","cardiovascular-health","clinical-trials"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Pooled analysis of semaglutide trials showed HR 0.79 (95% CI: 0.69-0.91) for MACE. Predictive modeling forecasts the 9,642-patient SOUL trial will achieve its primary endpoint by 3.78 years, suggesting early termination.","whyItMatters":"If confirmed, oral semaglutide's cardiovascular benefits would make an effective heart-protective diabetes and weight-loss drug available in pill form — dramatically improving access compared to injectable formulations and potentially changing prescribing patterns.","specificNumbers":"SOUL is a multicenter, double-blind, placebo-controlled RCT. The primary endpoint is major adverse cardiac events (MACE).","methodology":"Random-effects meta-analysis of prior semaglutide RCTs pooling hazard ratios. Matched placebo-arm cardiovascular event rates with SOUL trial assumptions to build a predictive model for trial duration and primary events.","limitations":"Predictive models depend on assumptions that may not hold. The meta-analysis pooled injectable semaglutide data to predict oral semaglutide outcomes. Real-world trial dynamics (dropout, protocol amendments) can affect actual timelines. This is a prediction, not a result."},{"rthcId":"RPEP-09283","title":"The transition of medication overuse status by acute medication categories in episodic or chronic migraine patients to non-overuse status after receiving anti-CGRP monoclonal antibodies: a systematic review and meta-analysis of phase 3 randomized control trial.","authors":"Sirilertmekasakul, Chananchida; Panto, Akkanat; Lekhalawan, Pattanan; Panyarachun, Pariyada; Jindasakchai, Porpim; Rattanawong, Wanakorn","year":2024,"journal":"Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 45(9), 4451-4462","doi":"10.1007/s10072-024-07496-7","pmid":"38564060","tags":["cgrp","clinical-trials","pain"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Anti-CGRP antibodies increased transition from medication overuse to non-overuse status by 44% overall (RR: 1.44), with the strongest effect in triptan overusers (RR: 1.71) but no significant effect for simple analgesic overusers.","whyItMatters":"Medication overuse headache affects up to 2% of the general population and is notoriously difficult to treat. Knowing that CGRP antibodies can help patients break the overuse cycle — particularly for triptan users — gives clinicians a specific, evidence-based intervention for this challenging condition.","specificNumbers":"The analysis included phase 3 RCTs. Patients overusing triptans responded most effectively to anti-CGRP antibody treatment.","methodology":"Systematic review and meta-analysis of 5 phase III RCTs from PubMed (January 2013 - September 2023). Included eptinezumab, fremanezumab, galcanezumab, and erenumab. Analyzed by acute headache medication categories: triptans, simple analgesics, and multiple drugs.","limitations":"Only 5 studies met inclusion criteria. The medication overuse analyses were secondary outcomes in trials designed for other primary endpoints. The meta-analysis couldn't distinguish between the four CGRP antibodies. The lack of effect on simple analgesic overuse needs explanation."},{"rthcId":"RPEP-09284","title":"Effectiveness of glucagon-like peptide-1 receptor agonists for reduction of body mass index and blood glucose control in patients with type 2 diabetes mellitus and obesity: A retrospective cohort study and difference-in-difference analysis.","authors":"Siriyotha, Sukanya; Anothaisintawee, Thunyarat; Looareesuwan, Panu; Nimitphong, Hataikarn; McKay, Gareth J; Attia, John; Thakkinstian, Ammarin","year":2024,"journal":"BMJ open, 14(11), e086424","doi":"10.1136/bmjopen-2024-086424","pmid":"39581734","tags":["glp-1-receptor-agonists","weight-management","type-2-diabetes"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"GLP-1RAs reduced BMI by 1.02 kg/m² (95% CI: -1.46 to -0.58), FPG by 21.34 mg/dL (95% CI: -29.53 to -13.15), and HbA1c by 0.58% (95% CI: -0.77 to -0.38) more than other second-line treatments over 24 months.","whyItMatters":"Clinical trials show GLP-1 drugs work, but real-world confirmation is essential because trial patients are carefully selected. This study confirms that the benefits translate to everyday clinical practice and quantifies the advantage over other second-line options.","specificNumbers":"Study period: 2010-2023. Used linear mixed-effect regression with heterogeneous augmented inverse probability weighting for robust comparisons.","methodology":"Retrospective cohort study using difference-in-differences analysis with heterogeneous augmented inverse probability weighting. 1,000 patients with T2DM (220 GLP-1RA, 880 non-GLP-1RA) from 2010-2023.","limitations":"Retrospective design with potential for unmeasured confounders. Unequal group sizes (220 vs 880). Specific GLP-1RA agents were not separately analyzed. 24-month follow-up may not capture long-term outcomes. Single healthcare setting."},{"rthcId":"RPEP-09285","title":"Matrikines in the skin: Origin, effects, and therapeutic potential.","authors":"Sirois, Jonathan P; Heinz, Andrea","year":2024,"journal":"Pharmacology & therapeutics, 260, 108682","doi":"10.1016/j.pharmthera.2024.108682","pmid":"38917886","tags":["collagen-peptides","skin-health","wound-healing"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Matrikines derived from ECM protein degradation actively regulate skin cell behavior through specific signaling pathways, with demonstrated therapeutic potential in melanoma, chronic wounds, inflammatory skin diseases, and anti-aging applications.","whyItMatters":"Understanding matrikines reframes skin aging and disease as partly driven by ECM degradation products — not just ECM loss. This creates opportunities for targeted therapies that either mimic beneficial matrikines or block harmful ones.","specificNumbers":"Review covers multiple matrikine types from different extracellular matrix proteins including collagen, elastin, and others.","methodology":"Comprehensive narrative review of published literature on matrikines in skin, covering their ECM origins, biological effects, and therapeutic applications across dermatology.","limitations":"Review article — no new experimental data. Most matrikine research is preclinical. Translation to clinical products has been limited, particularly for therapeutic (vs. cosmetic) applications. The complexity of ECM degradation makes it difficult to study individual matrikines in isolation."},{"rthcId":"RPEP-09286","title":"The impact of tirzepatide and glucagon-like peptide 1 receptor agonists on oral hormonal contraception.","authors":"Skelley, Jessica W; Swearengin, Katelyn; York, Adriane L; Glover, Lacey H","year":2024,"journal":"Journal of the American Pharmacists Association : JAPhA, 64(1), 204-211.e4","doi":"10.1016/j.japh.2023.10.037","pmid":"37940101","tags":["glp-1-receptor-agonists","safety-and-side-effects","hormones-and-signaling"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Tirzepatide significantly reduced oral contraceptive absorption (AUC, Cmax, and Tmax) while 5 studies of other GLP-1 RAs showed no clinically significant interaction with oral hormonal contraceptives.","whyItMatters":"Millions of women of reproductive age will take GLP-1 drugs for obesity and diabetes. If tirzepatide reduces birth control pill effectiveness, the consequences could be unintended pregnancies. Prescribers and patients need to know about this interaction and plan accordingly.","specificNumbers":"Tirzepatide's gastric emptying delay is most substantial after the first dose, with tachyphylaxis (tolerance) developing after subsequent doses.","methodology":"Literature review of 6 clinical trials from PubMed and Google Scholar examining interactions between incretin agents and oral hormonal contraceptives.","limitations":"Only 6 clinical trials available for review. The tirzepatide-contraceptive interaction was from a single study. The clinical significance of the reduced absorption (whether it actually leads to contraceptive failure) is not directly established. Other GLP-1 drugs may have less data available."},{"rthcId":"RPEP-09287","title":"Kisspeptin a potential therapeutic target in treatment of both metabolic and reproductive dysfunction.","authors":"Sliwowska, Joanna Helena; Woods, Nicola Elizabeth; Alzahrani, Abdullah Rzgallah; Paspali, Elpiniki; Tate, Rothwelle Joseph; Ferro, Valerie Anne","year":2024,"journal":"Journal of diabetes, 16(4), e13541","doi":"10.1111/1753-0407.13541","pmid":"38599822","tags":["kisspeptin","hormones-and-signaling","appetite-and-metabolism","reproductive-health"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Kisspeptins regulate both reproduction and metabolism in a sexually dimorphic manner, with disruptions in metabolic conditions leading to simultaneous reproductive dysfunction. Only 15% of clinical studies address kisspeptin's metabolic role.","whyItMatters":"Many metabolic disorders coexist with reproductive problems (e.g., PCOS with insulin resistance, obesity with hypogonadism). A peptide that links both systems could enable treatments addressing root causes rather than treating metabolic and reproductive issues separately.","specificNumbers":"Kisspeptin acts through receptors in the brain, brown adipose tissue, and pancreas.","methodology":"Narrative review of experimental (animal model) and clinical evidence on kisspeptin's dual role in metabolism and reproduction, covering diabetes, obesity, undernutrition, PCOS, and hypogonadism.","limitations":"Narrative review with limited systematic methodology. Clinical evidence for metabolic effects of kisspeptin is still sparse. The sexual dimorphism in kisspeptin's metabolic actions complicates therapeutic development. Most metabolic data comes from animal models."},{"rthcId":"RPEP-09288","title":"The pharmacological basis for nonpeptide agonism of the GLP-1 receptor by orforglipron.","authors":"Sloop, Kyle W; Cox, Amy L; Wainscott, David B; White, Alex; Droz, Brian A; Stutsman, Cynthia; Showalter, Aaron D; Suter, Todd M; Dunbar, James D; Snider, Brandy M; O'Farrell, Libbey S; Hewitt, Natalie; Ruble, J Craig; Padgett, Leah R; Woerly, Eric M; Peterson, Jeffrey A; Coskun, Tamer; Liu, Zhaomin; Coutant, David E; Ai, Minrong; Emmerson, Paul J; Sangwung, Panjamaporn; Willard, Francis S","year":2024,"journal":"Science translational medicine, 16(778), eadp5765","doi":"10.1126/scitranslmed.adp5765","pmid":"39693407","tags":["glp-1-receptor-agonists","drug-delivery","bioavailability"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Orforglipron binds GLP-1R with Ki=1 nM, achieves full biological response at low receptor occupancy, has minimal β-arrestin recruitment, and can sustain semaglutide-initiated weight loss when given orally.","whyItMatters":"An effective oral GLP-1 drug that doesn't require injection would dramatically expand access to obesity and diabetes treatment. Understanding orforglipron's unique pharmacology — particularly its biased signaling profile — could inform design of the next generation of nonpeptide agonists.","specificNumbers":"Orforglipron is in clinical development for type 2 diabetes and obesity. It is one of the first molecules in the GLP-1 receptor non-peptide agonist class.","methodology":"In vitro binding and signaling assays. In vivo glucose tolerance and weight loss studies in humanized GLP-1R mice and CRISPR-edited rats (Glp1rS33W). Crossover study comparing oral orforglipron with subcutaneous semaglutide.","limitations":"Preclinical pharmacology study — human clinical efficacy and safety data are still being generated. CRISPR-modified rat models are an imperfect proxy for human GLP-1R. The relationship between receptor occupancy and clinical efficacy in humans needs confirmation."},{"rthcId":"RPEP-09289","title":"Utilization, Expenditure, and Treatment Patterns Associated With Calcitonin Gene-Related Peptide Monoclonal Antibodies Reimbursed Subject to a Managed Access Protocol in Ireland.","authors":"Smith, Amelia; Finnigan, Karen; Clarke, Sarah; Barry, Michael; Gorry, Claire","year":2024,"journal":"Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research, 27(8), 1039-1045","doi":"10.1016/j.jval.2024.04.002","pmid":"38615937","tags":["cgrp","clinical-trials","safety-and-side-effects"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"96.1% approval rate for CGRP mAb applications. ~90% adherence rate. >75% persistence beyond 12 months. €3.2 million first-year expenditure under managed access in Ireland.","whyItMatters":"Demonstrating that managed access can successfully balance patient access with cost containment gives other healthcare systems a model for introducing expensive peptide-based therapies. The high adherence and persistence rates also suggest these drugs are genuinely benefiting patients.","specificNumbers":"Patients must have failed 3 or more previous treatments to qualify. Data extracted from national pharmacy claims databases.","methodology":"Analysis of claims data from Ireland's Primary Care Reimbursement Service High Tech database and drug request system (September 2021 - April 2023). Evaluated persistence via refill patterns and adherence via proportion of days covered.","limitations":"Single-country study (Ireland). No clinical outcome data (headache days, quality of life) — only utilization metrics. The managed access criteria (3+ prior treatment failures) create a selected population. No comparison to outcomes without managed access restrictions."},{"rthcId":"RPEP-09290","title":"Antifungal peptide-loaded alginate microfiber wound dressing evaluated against Candida albicans in vitro and ex vivo.","authors":"Snyder, Sabrina S; Rock, Crystal A; Millenbaugh, Nancy J","year":2024,"journal":"European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 205, 114578","doi":"10.1016/j.ejpb.2024.114578","pmid":"39532211","tags":["antimicrobial-peptides","wound-healing","drug-delivery"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"dKn2-7-loaded alginate fibers achieved 99% reduction in Candida albicans biofilms on ex vivo porcine skin at 500 µg/mg loading, with no significant tissue damage and preserved hemostatic function.","whyItMatters":"Fungal wound infections are increasingly common and difficult to treat, especially in immunocompromised patients. A wound dressing that simultaneously provides hemostasis, wound healing support, and sustained antifungal peptide delivery could address a critical unmet clinical need.","specificNumbers":"The dressing uses dKn2-7, a synthetic antifungal peptide, incorporated into calcium alginate microfibers for extended release.","methodology":"In vitro and ex vivo study: dKn2-7 loaded into calcium alginate microfibers at varying concentrations. Characterized release kinetics, calcium release, planktonic and biofilm killing (in vitro), and biofilm reduction on porcine skin (ex vivo). Histological assessment for tissue damage.","limitations":"Ex vivo porcine skin model — not tested in live wounds. The burst release profile may not provide sustained antifungal coverage beyond 24 hours. Only tested against C. albicans — other fungal pathogens may respond differently. Manufacturing scalability not addressed."},{"rthcId":"RPEP-09291","title":"Combined biolistic and cell penetrating peptide delivery for the development of scalable intradermal DNA vaccines.","authors":"So, Roizza Beth; Li, Gang; Brentville, Victoria; Daly, Janet M; Dixon, James E","year":2024,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 367, 209-222","doi":"10.1016/j.jconrel.2024.01.031","pmid":"38244841","tags":["cell-penetrating-peptides","drug-delivery","immune-system"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"GET peptide-coated gene gun bullets achieved 13-17-fold higher gene expression than standard bullets and successfully delivered a SARS-CoV-2 DNA vaccine that generated spike-specific T-cell and antibody responses in mice.","whyItMatters":"Pandemic preparedness requires rapidly deployable vaccine platforms. A scalable gene gun system using freeze-dried, peptide-enhanced DNA bullets could enable mass vaccination without cold chain requirements — critical for global health emergencies.","specificNumbers":"The GET system uses fusion peptides with cell-binding, nucleic acid condensing, and cell-penetrating domains.","methodology":"In vitro optimization in cell monolayers, engineered tissue, and DC2.4 dendritic cells. Freeze-dried bullet formulation. In vivo testing in mice for gene expression and SARS-CoV-2 DNA vaccine immune response evaluation.","limitations":"Mouse study — immune responses may not directly predict human protection. Gene gun delivery requires specialized equipment. The SARS-CoV-2 vaccine responses were comparable to conventional gene gun (not vastly superior). Manufacturing scalability still needs to be demonstrated at commercial scale."},{"rthcId":"RPEP-09292","title":"A Rare Case of Tirzepatide-Induced Hepatotoxicity.","authors":"Sohal, Aalam; Casanova, Luis; Kowdley, Kris V","year":2024,"journal":"ACG case reports journal, 11(10), e01484","doi":"10.14309/crj.0000000000001484","pmid":"39372916","tags":["glp-1-receptor-agonists","safety-and-side-effects","liver-health"],"studyType":"case series","evidenceStrength":"preliminary","keyFinding":"First reported case of tirzepatide-induced hepatotoxicity in a 37-year-old woman with metabolic syndrome, notable because tirzepatide typically reduces liver fat content.","whyItMatters":"As tirzepatide prescriptions rapidly increase for both diabetes and obesity, clinicians need to be aware that liver damage is a possible adverse effect — even though the drug generally improves liver metrics. Liver function monitoring should be part of routine care.","specificNumbers":"First reported case in the literature. Tirzepatide was recently FDA-approved for both type 2 diabetes and obesity.","methodology":"Single case report documenting clinical presentation of elevated liver enzymes, diagnostic workup to exclude other causes, and attribution to tirzepatide use.","limitations":"Single case report — cannot determine incidence or risk factors. The mechanism of hepatotoxicity was not investigated. Other contributing factors to liver enzyme elevation may not have been fully excluded. The temporal relationship supports but does not prove causation."},{"rthcId":"RPEP-09293","title":"'The effect of neuropeptide Y1 receptor agonist on hypothalamic neurogenesis in rat experimental depression model'.","authors":"Solak, Hatice; Gormus, Z Isik Solak; Koca, Raviye Ozen; Gunes, Canan Eroglu; Iyisoy, Mehmet Sinan; Kurar, Ercan; Kutlu, Selim","year":2024,"journal":"Metabolic brain disease, 40(1), 39","doi":"10.1007/s11011-024-01445-1","pmid":"39576364","tags":["neuropeptides","brain-and-cognition","mental-health"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"NPY Y1 receptor agonist treatment increased hypothalamic NPY gene expression and improved active swimming behavior in the forced swim test in chronically stressed rats, while depression alone decreased expression of IGF1R, FGF2, POMC, NPY, and GLUT2 genes.","whyItMatters":"Depression involves measurable neurochemical changes in the brain that go beyond mood — including decreased growth factor and neuropeptide expression. This study identifies the NPY Y1 receptor as a specific target that could help reverse these changes, potentially opening a new avenue for antidepressant treatment that works through a different mechanism than current medications.","specificNumbers":"The study used the CMS depression model and measured neurogenesis markers in the hypothalamus after NPY1R agonist treatment.","methodology":"Animal study using 48 male Wistar rats divided into 4 groups (Control, Depression, Depression + NPY1R, NPY1R only). Depression was induced via 30 days of chronic mild stress. NPY1R agonist was delivered via subcutaneous osmotic mini-pump at 130 μl/kg/day for 15 days. Behavioral assessments included open field test, forced swim test, and elevated plus maze. Hypothalamic gene expression was measured by quantitative RT-PCR.","limitations":"This is an animal study using only male rats, so findings may not directly translate to humans or account for sex differences in depression. The chronic mild stress model, while widely used, doesn't fully replicate human depression. The study measured gene expression but didn't assess whether actual protein levels or neurogenesis rates changed proportionally."},{"rthcId":"RPEP-09294","title":"Current Understanding of Sodium N-(8-[2-Hydroxylbenzoyl] Amino) Caprylate (SNAC) as an Absorption Enhancer: The Oral Semaglutide Experience.","authors":"Solis-Herrera, Carolina; Kane, Michael P; Triplitt, Curtis","year":2024,"journal":"Clinical diabetes : a publication of the American Diabetes Association, 42(1), 74-86","doi":"10.2337/cd22-0118","pmid":"38230324","tags":["glp-1-receptor-agonists","semaglutide","drug-delivery","bioavailability"],"studyType":"review","evidenceStrength":"strong","keyFinding":"SNAC technology works by three mechanisms: raising local gastric pH to protect semaglutide from acid degradation, shielding the peptide from enzymatic breakdown, and enhancing transcellular absorption across the stomach epithelium — together enabling clinically effective oral delivery of a GLP-1 receptor agonist.","whyItMatters":"The ability to take a GLP-1 receptor agonist as a daily pill instead of a weekly injection removes a major barrier to treatment. Many patients with type 2 diabetes are reluctant to start injectable therapies. SNAC technology represents a breakthrough in oral peptide delivery that could be applied to other peptide drugs beyond semaglutide.","specificNumbers":"Oral semaglutide was FDA-approved in 2019. SNAC stands for sodium N-(8-[2-hydroxylbenzoyl] amino) caprylate.","methodology":"Narrative review summarizing published studies on SNAC technology as an absorption enhancer, focusing on its application in the oral semaglutide formulation (Rybelsus). Covers preclinical absorption studies and clinical pharmacokinetic data.","limitations":"SNAC-based oral semaglutide has lower bioavailability compared to injectable semaglutide, requiring higher doses. The strict dosing requirements (empty stomach, minimal water, 30-minute fast) may reduce real-world adherence. This is a narrative review, not a systematic review with formal quality assessment of included studies."},{"rthcId":"RPEP-09295","title":"Effect of Semaglutide on Cardiac Structure and Function in Patients With Obesity-Related Heart Failure.","authors":"Solomon, Scott D; Ostrominski, John W; Wang, Xiaowen; Shah, Sanjiv J; Borlaug, Barry A; Butler, Javed; Davies, Melanie J; Kitzman, Dalane W; Verma, Subodh; Abildstrøm, Steen Z; Nygaard Einfeldt, Mette; Rasmussen, Søren; Abhayaratna, Walter P; Ahmed, Fozia Z; Ben-Gal, Tuvia; Chopra, Vijay; Ito, Hiroshi; Merkely, Bela; Núñez, Julio; Senni, Michele; van der Meer, Peter; Wolf, Dennis; Petrie, Mark C; Kosiborod, Mikhail N","year":2024,"journal":"Journal of the American College of Cardiology, 84(17), 1587-1602","doi":"10.1016/j.jacc.2024.08.021","pmid":"39217567","tags":["glp-1-receptor-agonists","semaglutide","cardiovascular-health"],"studyType":"RCT","evidenceStrength":"strong","keyFinding":"Semaglutide 2.4 mg weekly significantly reduced left atrial volume progression (-6.13 mL vs placebo, p=0.0013), right ventricular enlargement (RV end-diastolic area -1.99 cm², p=0.016), and improved diastolic filling parameters (E-wave velocity -5.63 cm/s, p=0.0037; E/A ratio -0.14, p=0.0075) over 52 weeks.","whyItMatters":"HFpEF is the most common form of heart failure and has had very few effective treatments. This study provides the first evidence that semaglutide may be genuinely disease-modifying in obesity-related HFpEF — not just improving symptoms through weight loss, but actually reversing harmful structural changes in the heart.","specificNumbers":"Semaglutide dose: 2.4 mg once weekly. Study population: patients with obesity-related HFpEF.","methodology":"Prespecified echocardiography substudy of pooled STEP-HFpEF and STEP-HFpEF DM randomized controlled trials. 491 of 1,145 participants had echocardiograms at baseline and 52 weeks. Treatment effects assessed using analysis of covariance stratified by trial and BMI, adjusted for baseline values.","limitations":"Only 43% of trial participants had echocardiographic data at both timepoints, raising questions about selection bias. The study was not independently powered for the echocardiographic endpoints. Effects on LV dimensions, mass, and systolic function were not significant. Longer follow-up needed to determine if structural improvements translate to reduced cardiovascular events."},{"rthcId":"RPEP-09296","title":"Neuropeptide Y in first-episode schizophrenia: is there any sex differences in the pathogeneses of schizophrenia?","authors":"Song, Jia-Qi; Xin, Wen; Yu, Jian-Jin; Zhao, Qing; Li, Hong-Na; Chen, Da-Chun","year":2024,"journal":"Frontiers in psychiatry, 15, 1514475","doi":"10.3389/fpsyt.2024.1514475","pmid":"39691787","tags":["neuropeptides","mental-health","brain-and-cognition"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Serum NPY levels were significantly higher in first-episode schizophrenia patients than controls (p<0.001). In males, NPY positively correlated with PANSS symptom scores at baseline (p<0.01) and changes in NPY tracked with symptom changes during risperidone treatment (p<0.05). No such correlations were found in females. The NPY × sex interaction was highly significant (p<0.001).","whyItMatters":"Understanding sex differences in schizophrenia has been a long-standing challenge. This study provides concrete biological evidence that neuropeptide Y — a molecule involved in stress response and brain signaling — behaves differently in male versus female schizophrenia patients. This could eventually lead to sex-specific treatment approaches.","specificNumbers":"115 first-episode schizophrenia patients and 58 matched healthy controls. NPY measured at baseline and after 10 weeks of risperidone treatment.","methodology":"Case-control cohort study with 115 first-episode schizophrenia patients and 58 matched healthy controls. Serum NPY measured at baseline and after 10 weeks of risperidone treatment in patients. Symptoms assessed with the Positive and Negative Syndrome Scale (PANSS). 95 patients completed the full study protocol.","limitations":"Moderate sample size with only 95 completing follow-up. All patients were treated with risperidone, so findings may not generalize to other antipsychotics. Serum NPY may not fully reflect brain NPY levels. The study didn't control for potential confounders like hormonal status in female patients. First-episode patients may differ from chronic schizophrenia populations."},{"rthcId":"RPEP-09297","title":"Analysing the effects of National Centralised Drug Procurement and Price Negotiation Policies on novel hypoglycaemic drug usage and costs in Shanghai, China: an interrupted time series analysis.","authors":"Song, Jie; Guo, Wei; Jin, Chunlin; Xu, Yuan; Hu, Xiaojing; Zhang, Zheng; Lin, Hai","year":2024,"journal":"BMJ open, 14(12), e088318","doi":"10.1136/bmjopen-2024-088318","pmid":"39627122","tags":["glp-1-receptor-agonists","type-2-diabetes","clinical-trials"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"National price negotiation led to a significant increase of 212.28 defined daily doses (95% CI: 188.25-236.31, p<0.001) in novel hypoglycaemic drug consumption. Daily costs decreased significantly after policy implementation (p<0.001). Dulaglutide, liraglutide, semaglutide, and dapagliflozin showed significant increases in utilization post-policy (p<0.001).","whyItMatters":"Drug pricing policy directly affects whether patients can access effective medications. This real-world evidence shows that government price negotiation can dramatically expand access to GLP-1 receptor agonists — drugs that have proven benefits for diabetes, obesity, and cardiovascular disease — by making them affordable at scale.","specificNumbers":"Study period: January 2016 to December 2022 in Shanghai. Multiple rounds of national drug procurement and price negotiation policies were analyzed.","methodology":"Interrupted time series analysis with segmented regression using drug procurement data from the Shanghai Medical Procurement Agency covering all public and private hospitals in Shanghai, January 2016 to December 2022. Analyzed volume, expenditure, and daily cost changes for specific drugs relative to policy implementation dates.","limitations":"Data is from Shanghai only, which is more developed than most Chinese cities — results may not generalize to rural or less economically developed regions. The study measures procurement volumes, not individual patient outcomes or adherence. It cannot distinguish whether increased utilization led to improved health outcomes. The study period ended in 2022 and doesn't capture the more recent semaglutide demand surge."},{"rthcId":"RPEP-09298","title":"Predictive factors of response to liraglutide in patients with type 2 diabetes mellitus and metabolic syndrome.","authors":"Song, Jinfang; Li, Na; Zhuang, Yongru; Chen, Ya; Zhang, Chu; Zhu, Jian","year":2024,"journal":"Frontiers in endocrinology, 15, 1449558","doi":"10.3389/fendo.2024.1449558","pmid":"39429734","tags":["glp-1-receptor-agonists","type-2-diabetes","personalized-medicine"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Baseline HbA1c, baseline BMI, and duration of type 2 diabetes were significant predictors of liraglutide response (p<0.05). The combined ROC area under the curve was 0.851 (95% CI: 0.793-0.910), indicating good predictive accuracy.","whyItMatters":"Not everyone responds equally to GLP-1 drugs, and they're expensive. Identifying simple, readily available clinical markers that predict who will benefit most helps clinicians make more informed prescribing decisions and set realistic expectations for patients starting liraglutide.","specificNumbers":"Minimum treatment duration: 6 months. Population: patients with both type 2 diabetes and metabolic syndrome.","methodology":"Retrospective cohort study of 417 patients with T2DM and metabolic syndrome receiving liraglutide for 6+ months. Of these, 206 completed follow-up. Responders were defined as achieving HbA1c reduction ≥1.0% AND weight loss ≥3%. Binary logistic regression identified predictive factors, validated by ROC analysis.","limitations":"Retrospective design with nearly half of enrolled patients lost to follow-up (211 of 417). Single-center study from China may not generalize to other populations. The response definition (HbA1c ≥1% + weight ≥3%) is somewhat arbitrary. Didn't account for diet, exercise, or medication adherence, which significantly affect outcomes."},{"rthcId":"RPEP-09299","title":"Design and Evaluation of Synthetic Delivery Formulations for Peptide-Based Cancer Vaccines.","authors":"Song, Kefan; Pun, Suzie H","year":2024,"journal":"BME frontiers, 5, 0038","doi":"10.34133/bmef.0038","pmid":"38515636","tags":["peptide-vaccines","cancer-therapy","drug-delivery","immune-system"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Three main barriers limit peptide vaccine efficacy: rapid clearance, low immunogenicity, and insufficient uptake by antigen-presenting cells. Synthetic delivery systems targeting lymph node drainage, APC delivery, cross-presentation, and adjuvant incorporation can overcome these barriers and significantly improve anti-tumor immune responses in preclinical models.","whyItMatters":"Cancer immunotherapy is revolutionizing oncology, and personalized peptide vaccines based on patient-specific neoantigens represent a promising frontier. Solving the delivery problem is the key bottleneck — without effective delivery, even the best cancer vaccine antigen won't generate a strong enough immune response to fight tumors.","specificNumbers":"Review covers barriers including rapid clearance, low immunogenicity, and insufficient APC uptake, with strategies targeting lymph node drainage.","methodology":"Narrative review evaluating the current landscape of synthetic delivery formulations for peptide cancer vaccines, covering design principles, preclinical evaluation strategies, vaccine administration routes, and murine tumor models used in testing.","limitations":"Primarily covers preclinical data with limited human clinical trial evidence. Many delivery systems that work in mouse models face challenges in translation to humans. The review focuses on synthetic delivery systems and may underrepresent biological delivery approaches."},{"rthcId":"RPEP-09300","title":"Effect of Tight Junction-Modulating FCIGRL-Modified Peptides on the Intestinal Absorption of Doxorubicin in Rats.","authors":"Song, Keon-Hyoung","year":2024,"journal":"Pharmaceutics, 16(5)","doi":"10.3390/pharmaceutics16050650","pmid":"38794312","tags":["cell-penetrating-peptides","drug-delivery","bioavailability","cancer-therapy"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Pep4 with levan increased doxorubicin AUC by 2.38-fold (p<0.05) and Cmax by 3.30-fold (p<0.01) compared to control. Pep2 with levan/benzalkonium chloride and Pep3 with levan also significantly enhanced absorption. The peptides work by temporarily opening tight junctions between intestinal epithelial cells.","whyItMatters":"Many life-saving drugs, including chemotherapy agents, must be given intravenously because they can't cross the intestinal barrier. If peptide-based absorption enhancers can safely enable oral delivery of these drugs, it would dramatically improve patient quality of life, reduce healthcare costs, and potentially improve treatment adherence.","specificNumbers":"Four peptide variants (Pep1-Pep4) derived from the six-mer sequence FCIGRL were tested alongside doxorubicin.","methodology":"Animal pharmacokinetic study in rats receiving intraduodenal administration of doxorubicin with each FCIGRL-modified peptide (Pep1-Pep4) combined with stabilizers levan or benzalkonium chloride. Blood levels were measured over 240 minutes to calculate AUC and Cmax.","limitations":"Animal study with intraduodenal delivery (bypassing stomach acid), so oral tablet performance may differ significantly. The tight junction opening is reversible, but safety of repeated daily dosing wasn't assessed. Single-dose pharmacokinetic study — chronic efficacy and toxicity unknown. Clinical translation from rats to humans requires additional studies."},{"rthcId":"RPEP-09301","title":"Preparation, Biological Activities, and Potential Applications of Hen Egg-Derived Peptides: A Review.","authors":"Song, Li; Chen, Yi; Liu, Huiping; Zhang, Xiaowei","year":2024,"journal":"Foods (Basel, Switzerland), 13(6)","doi":"10.3390/foods13060885","pmid":"38540877","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09302","title":"Multiomics analysis of canine myocardium after circumferential pulmonary vein ablation: Effect of neuropeptide Y on long-term reinduction of atrial fibrillation.","authors":"Song, Qiyuan; Zhang, Ning; Zhang, Yujiao; Zhang, An; Li, Huilin; Bai, Shuting; Shang, Luxiang; Du, Juanjuan; Hou, Yinglong","year":2024,"journal":"Journal of cellular and molecular medicine, 28(15), e18582","doi":"10.1111/jcmm.18582","pmid":"39107876","tags":["neuropeptides","cardiovascular-health"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Multi-omics profiling identified NPY as significantly downregulated after pulmonary vein ablation. NPY suppression promoted cardiomyocyte apoptosis and activated the Akt pathway in cardiac fibroblasts, increasing fibrosis. NPY intervention alleviated atrial myocyte apoptosis and inhibited Akt activation in fibroblasts. The atrial effective refractory period was shortened after ablation.","whyItMatters":"Atrial fibrillation affects millions worldwide and catheter ablation is a primary treatment, yet recurrence rates remain frustratingly high. Understanding that NPY suppression after ablation actively promotes the conditions for recurrence opens a potential therapeutic avenue — supplementing NPY could help prevent AF from coming back.","specificNumbers":"The study used transcriptome and proteome profiling via high-throughput sequencing and TMT-tagged LC-MS analysis in a long-term canine model.","methodology":"Animal study using a long-term beagle dog model after circumferential pulmonary vein ablation (CPVA). Transcriptome profiling via high-throughput sequencing and proteome analysis via TMT-tagged LC-MS. Differentially expressed genes and proteins were identified, with NPY selected for functional validation in cell experiments and tissue analysis.","limitations":"Canine model may not fully replicate human cardiac physiology after ablation. The number of dogs used was not specified. The molecular pathway (NPY → apoptosis/fibrosis → AF reinduction) is proposed but the causal chain needs further validation. Translating NPY supplementation to human therapy faces significant pharmacological challenges."},{"rthcId":"RPEP-09303","title":"A novel angiotensin I-converting enzyme inhibitory peptide APPLRP from Grifola frondosa ameliorated the Ang II-induced vascular modeling in zebrafish model by mediating smooth muscle cells.","authors":"Song, Tianyuan; Zhang, Tiantian; Cai, Qiaolin; Ding, Yin-Yi; Gu, Zhenyu","year":2024,"journal":"International journal of biological macromolecules, 278(Pt 4), 134998","doi":"10.1016/j.ijbiomac.2024.134998","pmid":"39181368","tags":["bioactive-peptides","cardiovascular-health","antioxidant-effects"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"APPLRP is a competitive ACE inhibitor with IC50 of 29.93 μM that resists pepsin and pancreatin digestion. In hypertensive zebrafish, it reduced cardiac fibrosis, increased vessel diameter, decreased vessel wall thickness, downregulated ACE expression, and upregulated protective ACE2 expression. In vitro, it blocked Ang II-induced smooth muscle cell proliferation via AT1R/ERK1/2/STAT3 pathway inhibition.","whyItMatters":"Finding natural food-derived peptides that can lower blood pressure offers potential alternatives or supplements to pharmaceutical ACE inhibitors. The fact that APPLRP survives digestion and works through multiple mechanisms — direct ACE inhibition plus vascular remodeling protection — makes it particularly promising as a functional food ingredient.","specificNumbers":"IC50 = 29.93 µM. The peptide was isolated from the alcohol-soluble fraction of Grifola frondosa.","methodology":"Multi-approach study: computational docking to ACE active site, in vitro smooth muscle cell experiments with Ang II stimulation, and in vivo zebrafish hypertension model with cardiac output, blood flow velocity, collagen deposition, and vessel morphometry measurements. Peptide digestive stability tested against pepsin and pancreatin.","limitations":"Zebrafish cardiovascular system differs significantly from human physiology. The IC50 of 29.93 μM, while active, is relatively high compared to pharmaceutical ACE inhibitors. Oral bioavailability in mammals needs testing — digestive stability doesn't guarantee absorption through the gut wall. No mammalian blood pressure data was collected."},{"rthcId":"RPEP-09304","title":"New perspectives on migraine treatment: a review of the mechanisms and effects of complementary and alternative therapies.","authors":"Song, Xiaoli; Zhu, Qian; Su, Lanqian; Shi, Lei; Chi, Hao; Yan, Yalan; Luo, Mei; Xu, Xibin; Liu, Baohong; Liu, Zhengyang; Yang, Jin","year":2024,"journal":"Frontiers in neurology, 15, 1372509","doi":"10.3389/fneur.2024.1372509","pmid":"38784897","tags":["cgrp","pain","natural-peptides"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Complementary and alternative therapies (CAT) show varying levels of evidence for migraine management, while novel peptide-targeting therapies (CGRP antagonists and monoclonal antibodies, PACAP antagonists) represent the most significant pharmacological advance in migraine treatment. The review proposes that CAT may serve as adjunctive therapy alongside these new peptide-based treatments.","whyItMatters":"Migraine treatment is being transformed by peptide-targeting drugs, but many patients also seek non-pharmacological options due to medication side effects or personal preference. Understanding how complementary therapies work alongside these new peptide-based drugs helps patients and clinicians design comprehensive, personalized treatment plans.","specificNumbers":"Women are more susceptible to migraine. Long-term NSAID use is the main first-line approach but leads to side effects and drug adaptation.","methodology":"Narrative review summarizing the pathophysiology of migraine, the mechanisms and evidence for various complementary and alternative therapies, and the potential of CGRP and PACAP antagonists as novel migraine treatments.","limitations":"As a narrative review, it doesn't systematically assess quality of evidence for each therapy. Many complementary therapies have limited high-quality RCT data. The discussion of CGRP/PACAP therapies is not exhaustive. Potential publication bias in alternative medicine studies is not addressed."},{"rthcId":"RPEP-09305","title":"LC-AMP-F1 Derived from the Venom of the Wolf Spider Lycosa coelestis, Exhibits Antimicrobial and Antibiofilm Activities.","authors":"Song, Yuxin; Wang, Junyao; Liu, Xi; Yu, Shengwei; Tang, Xing; Tan, Huaxin","year":2024,"journal":"Pharmaceutics, 16(1)","doi":"10.3390/pharmaceutics16010129","pmid":"38276499","tags":["antimicrobial-peptides","venom-derived-peptides"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"LC-AMP-F1 inhibited growth of various bacteria including 5 multidrug-resistant clinical strains, effectively inhibited biofilm formation, and disrupted mature biofilms. It showed synergistic or additive effects with conventional antibiotics, minimal hemolytic activity, and low eukaryotic cell toxicity. Mechanism: increased membrane permeability and rapid membrane disruption.","whyItMatters":"Antibiotic resistance is a global health crisis, and biofilm-associated infections are particularly difficult to treat. Finding new antimicrobial agents from natural sources like spider venom — especially ones that work against drug-resistant bacteria and biofilms while being safe for human cells — is critical for developing next-generation anti-infective therapies.","specificNumbers":"LC-AMP-F1 was derived from the cDNA library of Lycosa coelestis venom gland. It demonstrated both antimicrobial and antibiofilm activities.","methodology":"In vitro study characterizing a novel antimicrobial peptide from wolf spider venom cDNA library. Tested antimicrobial activity against standard and multidrug-resistant bacteria, biofilm inhibition and disruption, combination effects with antibiotics, hemolytic activity, cytotoxicity to eukaryotic cells, and stability. Mechanism studied via scanning electron microscopy and SYTOX Green membrane permeability staining.","limitations":"In vitro study only — no animal infection model data. The peptide's pharmacokinetics, in vivo stability, and therapeutic index in living organisms are unknown. Manufacturing costs for venom-derived peptides can be prohibitive. Resistance development to the peptide over time hasn't been assessed."},{"rthcId":"RPEP-09306","title":"Thymosin β4 promotes zebrafish Mauthner axon regeneration by facilitating actin polymerization through binding to G-actin.","authors":"Song, Zheng; Han, Along; Hu, Bing","year":2024,"journal":"BMC biology, 22(1), 244","doi":"10.1186/s12915-024-02045-2","pmid":"39443925","tags":["thymosin-beta-4","nerve-regeneration","wound-healing"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Tβ4 knockout impaired Mauthner cell axon regeneration in zebrafish, while overexpression promoted it. The mechanism requires Tβ4-G-actin binding and promotes actin polymerization (not depolymerization as some models predicted). Axon regeneration length correlated negatively with the straight-tail escape deficit. Tβ4 overexpression restored rapid escape behavior.","whyItMatters":"Central nervous system injuries in humans — spinal cord injuries, traumatic brain injuries — are currently irreversible because mammalian CNS axons don't regenerate. If Tβ4's mechanism of promoting nerve regeneration through actin assembly can be harnessed in humans, it could open new therapeutic avenues for some of the most devastating neurological injuries.","specificNumbers":"Used a single Mauthner cell axon injury model in zebrafish larvae with detailed actin polymerization analysis.","methodology":"In vivo study using zebrafish larvae Mauthner cell single axon injury model. CRISPR knockout and overexpression of Tβ4 with domain-specific mutants to test G-actin binding requirement. Functional assessment via rapid escape behavior test measuring tail bending (straight tail = impaired function). Actin polymerization assessed in regenerating axons.","limitations":"Zebrafish have inherently greater CNS regenerative capacity than mammals, so results may not directly translate. The Mauthner cell model is a specific large neuron type that may not represent all CNS neurons. The study didn't test whether Tβ4 works in mammalian spinal cord injury models. Adult zebrafish vs. larvae may show different regenerative responses."},{"rthcId":"RPEP-09307","title":"Euglycemic Ketoacidosis From Semaglutide in a Patient Without Diabetes.","authors":"Sood, Nikhil; Bansal, Ojas; Garg, Rohini; Hoskote, Abhinav","year":2024,"journal":"JCEM case reports, 2(9), luae156","doi":"10.1210/jcemcr/luae156","pmid":"39221223","tags":["glp-1-receptor-agonists","semaglutide","safety-and-side-effects"],"studyType":"case series","evidenceStrength":"preliminary","keyFinding":"First reported case of euglycemic ketoacidosis caused by semaglutide in a patient without diabetes. The patient presented with metabolic acidosis and ketonemia with normal blood glucose after 7 months of semaglutide for weight loss. Treatment with bicarbonate-containing dextrose infusion resolved the ketoacidosis rapidly.","whyItMatters":"Millions of non-diabetic patients are now taking semaglutide for weight loss. Euglycemic ketoacidosis is life-threatening and easily missed because blood sugar is normal — clinicians may not think to check for it. As GLP-1 prescribing continues to expand, recognizing this rare but serious complication could save lives.","specificNumbers":"Patient used semaglutide for 7 months for weight loss. She had no history of diabetes. Presented with metabolic acidosis and ketonemia with normal blood glucose.","methodology":"Single case report with literature review identifying only one prior case of GLP-1-related euglycemic ketoacidosis in a non-diabetic patient (with tirzepatide). Clinical presentation, lab findings, treatment, and outcome documented.","limitations":"Single case report — cannot establish causation definitively. Other contributing factors (fasting, low-carb diet, alcohol use, exercise patterns) may have played a role alongside semaglutide. The mechanism by which GLP-1 agonists might cause ketoacidosis in non-diabetic patients is not well understood."},{"rthcId":"RPEP-09308","title":"Cardiovascular Adverse Drug Reactions of Anti-Calcitonin Gene-Related Peptide Monoclonal Antibodies for Migraine Prevention: An Analysis from the European Spontaneous Adverse Event Reporting System.","authors":"Sorbara, Emanuela Elisa; Barbieri, Maria Antonietta; Russo, Giulia; Cicala, Giuseppe; Spina, Edoardo","year":2024,"journal":"BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy, 38(2), 275-285","doi":"10.1007/s40259-024-00651-8","pmid":"38402495","tags":["cgrp","cardiovascular-health","safety-and-side-effects"],"studyType":"cohort","evidenceStrength":"preliminary","keyFinding":"Among 9,441 ICSRs, 12.8% involved cardiovascular adverse events (1,205 reports, 1,599 CV ADRs). 67.5% of CV ADRs were serious. Disproportionate reporting: erenumab — hypertension (ROR 1.45); galcanezumab — atrial fibrillation (ROR 2.36), myocardial infarction (ROR 2.21); fremanezumab — deep vein thrombosis (ROR 3.86), pallor (ROR 5.00), palpitations (ROR 1.48). Several findings not in official drug labels.","whyItMatters":"CGRP has known cardiovascular functions including blood vessel dilation, so blocking it could theoretically affect heart and blood vessel function. These pharmacovigilance data provide the first large-scale real-world evidence of drug-specific cardiovascular risk patterns that differ across the anti-CGRP antibodies — information critical for prescribing decisions, especially in migraine patients with pre-existing cardiovascular conditions.","specificNumbers":"Data covered July 2018 to December 2022 from the EudraVigilance database, focusing specifically on cardiovascular adverse reactions.","methodology":"Pharmacovigilance disproportionality analysis of the EudraVigilance database (July 2018–December 2022). Reporting odds ratios (ROR) with 95% CI compared CV adverse event rates for each anti-CGRP mAb against all other monoclonal antibodies. Case-by-case analysis of serious CV reports examined seriousness, age, sex, and concomitant medications.","limitations":"Pharmacovigilance data has inherent biases: underreporting, reporting biases (newer drugs get more attention), inability to establish causation, and no denominator (total prescriptions) to calculate incidence. Erenumab's dominance (58.9% of reports) reflects its earlier market entry. The comparator group (all other mAbs) may not be ideal since different mAbs treat different diseases."},{"rthcId":"RPEP-09309","title":"Cathelicidin in Urinary Tract Diseases: Diagnostic, Prognostic and Therapeutic Potential of an Evolutionary Conserved Antimicrobial Protein.","authors":"Sorić Hosman, Iva; Cvitković Roić, Andrea; Vuković Brinar, Ivana; Gulin, Tonko; Ćorić, Marijana; Rogić, Dunja; Lončar Vrančić, Ana; Lamot, Lovro","year":2024,"journal":"Medicina (Kaunas, Lithuania), 60(12)","doi":"10.3390/medicina60122015","pmid":"39768895","tags":["antimicrobial-peptides","immune-system","infection-defense"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Cathelicidin is rapidly produced by uroepithelial cells upon pathogen contact, making it a potential early UTI biomarker. Post-UTI cathelicidin levels lower than healthy controls suggest a risk factor for recurrence. Cathelicidin also shows promise as a biomarker for severe vesicoureteral reflux and renal scarring. Multiple therapeutic agents that upregulate cathelicidin expression are under investigation.","whyItMatters":"With antibiotic resistance rising, leveraging the body's own antimicrobial defenses is increasingly important. Cathelicidin-based diagnostics could enable faster UTI detection than traditional culture methods, while cathelicidin-boosting therapies could reduce antibiotic dependence. Identifying patients with low cathelicidin levels could also enable preventive strategies for those prone to recurrent UTIs.","specificNumbers":"Cathelicidin is encoded by a single gene in humans (CAMP gene). UTIs are one of the most common infectious diseases worldwide.","methodology":"Comprehensive review searching Scopus, Medline, and Web of Science databases for all published studies on cathelicidin in urinary tract diseases, covering diagnostic, prognostic, and therapeutic applications.","limitations":"Review format inherently depends on the quality and quantity of available studies, which varies considerably across the different clinical applications discussed. Most cathelicidin biomarker studies have been relatively small. Therapeutic cathelicidin upregulation is still in early stages with limited clinical data. Standardization of cathelicidin measurement methods across studies remains a challenge."},{"rthcId":"RPEP-09310","title":"In vitro gastrointestinal stability and intestinal absorption of ACE-1 and DPP4 inhibitory peptides from poultry by-product hydrolysates.","authors":"Sorokina, Liudmila; Solberg, Nina Therese; Koga, Shiori; Rønning, Sissel Beate; Afseth, Nils Kristian; Wilson, Steven Ray; Rieder, Anne; Wubshet, Sileshi Gizachew","year":2024,"journal":"Food & function, 15(14), 7364-7374","doi":"10.1039/d4fo01214c","pmid":"38912915","tags":["bioactive-peptides","cardiovascular-health","bioavailability","type-2-diabetes"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Bioactive dipeptides YA, VL, and IY from poultry hydrolysates resisted simulated gastrointestinal digestion. However, Caco-2 cell monolayer absorption tests showed peptide concentrations decreased on the apical side but were not detected basolaterally — indicating cellular uptake/metabolism rather than transcellular transport. The peptides downregulated peptide transporter expression, CDX2 transcription factor, and tight junction protein TJP1.","whyItMatters":"Many food-derived peptides show impressive activity in lab tests but fail to deliver benefits when consumed orally because they can't reach the bloodstream in sufficient quantities. This study provides an important reality check: even peptides that survive digestion face a second major barrier — crossing the intestinal wall. Understanding this bottleneck is essential for developing effective nutraceutical peptide products.","specificNumbers":"The low molecular weight peptide fraction (LMWPF) showed dual ACE-1 and DPP-4 inhibitory activity with good digestive stability.","methodology":"In vitro study using INFOGEST static digestion model for gastrointestinal stability and Caco-2 cell monolayers for intestinal absorption. Peptide identification by LC-MS. Gene expression analysis of Caco-2 cells after peptide stimulation. 4-hour incubation period for transport studies.","limitations":"Caco-2 cells, while the gold standard for intestinal absorption studies, are cancer-derived cells that may not perfectly represent normal intestinal epithelium. The 4-hour timeframe may be insufficient to capture slow transcellular transport. The study used individual dipeptides rather than the complete hydrolysate, which may behave differently. No in vivo absorption data was collected."},{"rthcId":"RPEP-09311","title":"Discovery of peptides for ligand-mediated delivery of mRNA lipid nanoparticles to cystic fibrosis lung epithelia.","authors":"Soto, Melissa R; Lewis, Mae M; Leal, Jasmim; Pan, Yuting; Mohanty, Rashmi P; Veyssi, Arian; Maier, Esther Y; Heiser, Brittany J; Ghosh, Debadyuti","year":2024,"journal":"Molecular therapy. Nucleic acids, 35(4), 102375","doi":"10.1016/j.omtn.2024.102375","pmid":"39640013","tags":["cell-penetrating-peptides","drug-delivery","gene-therapy"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"A lead peptide identified from phage display against primary CF bronchial epithelial cells enhanced mRNA lipid nanoparticle delivery by 7.8-fold in vitro (primary human CF bronchial epithelia) and 3.4-fold in vivo (mouse lungs). The peptide facilitated specific uptake into lung epithelial cells relative to other cell types.","whyItMatters":"Gene therapy could potentially cure cystic fibrosis by delivering correct copies of the CFTR gene, but getting the therapeutic cargo past airway mucus and into the right cells has been the main technical barrier. This peptide-guided approach represents a significant step toward making lung-targeted gene therapy for CF a reality.","specificNumbers":"Screening was performed against primary human bronchial epithelial cells from CF patients cultured at air-liquid interface for realistic conditions.","methodology":"Phage display screening against primary human bronchial epithelial cells from CF patients cultured at air-liquid interface (producing mucus). Lead peptide incorporated into lipid nanoparticles carrying reporter mRNA (luciferase). Delivery efficiency measured in vitro on primary CF cells and in vivo in mouse lungs.","limitations":"Mouse lungs differ significantly from human CF lungs in mucus composition and thickness. The fold-improvements, while significant, may need to be larger for therapeutic efficacy. Long-term safety of repeated peptide-nanoparticle administration to the lungs is unknown. The study used reporter mRNA, not therapeutic CFTR mRNA."},{"rthcId":"RPEP-09312","title":"Small Effects, Questionable Outcomes: Bremelanotide for Hypoactive Sexual Desire Disorder.","authors":"Spielmans, Glen I; Ellefson, Elaine M","year":2024,"journal":"Journal of sex research, 61(4), 540-561","doi":"10.1080/00224499.2023.2175192","pmid":"36809187","tags":["melanocortin-peptides","clinical-trials","reproductive-health"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"8 of 11 clinicaltrials.gov-specified efficacy outcomes were unpublished, including FSDS-DAO total score, FSFI total score, FSFI arousal domain, and FSEP-R items. Analyzed unpublished outcomes showed effect sizes from nil to small. Published categorical response outcomes lacked validity evidence. Nearly all outcomes suggesting modest benefits were likely post-hoc.","whyItMatters":"Drug approval should be based on meaningful clinical outcomes measured by validated tools. This analysis raises concerns that bremelanotide was approved based on modest improvements in outcomes that may not actually measure what they claim to measure in the target population. This has broader implications for how drugs for sexual health conditions are evaluated.","specificNumbers":"Analysis examined the FSFI, FSFI-D (desire domain), and FSDS-DAO questionnaires used in the RECONNECT trials.","methodology":"Critical review and reanalysis of the Phase III RECONNECT bremelanotide trials. Examined measurement properties and validity evidence for all efficacy outcomes. Obtained and analyzed previously unpublished data from 8 of 11 pre-specified ClinicalTrials.gov outcomes. Evaluated whether published categorical response definitions had supporting validity evidence.","limitations":"This is a secondary analysis that cannot definitively prove the outcome measures are invalid — it can only demonstrate the absence of supporting validity evidence. The authors did not have access to individual patient data, limiting the depth of their reanalysis. Their critical perspective may underestimate clinically meaningful subjective improvements that are difficult to capture with standardized scales."},{"rthcId":"RPEP-09313","title":"The Emission of Internal Conversion Electrons Rather Than Auger Electrons Increased the Nucleus-Absorbed Dose for 161Tb Compared with 177Lu with a Higher Dose Response for [161Tb]Tb-DOTA-LM3 Than for [161Tb]Tb-DOTATATE.","authors":"Spoormans, Kaat; Struelens, Lara; Vermeulen, Koen; De Saint-Hubert, Marijke; Koole, Michel; Crabbé, Melissa","year":2024,"journal":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 65(10), 1619-1625","doi":"10.2967/jnumed.124.267873","pmid":"39209546","tags":["somatostatin-analogs","cancer-therapy","radionuclide-therapy"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"161Tb-DOTATATE and 161Tb-DOTA-LM3 delivered 3.6× and 3.8× higher nuclear absorbed doses than 177Lu-labeled counterparts. The enhanced dose was primarily from internal conversion electrons, not Auger electrons. 161Tb-DOTA-LM3 showed a superior linear-quadratic dose response (suggesting additional membrane damage) compared to the linear-only response of 161Tb-DOTATATE.","whyItMatters":"177Lu-DOTATATE is already an approved, effective treatment for neuroendocrine tumors. If 161Tb can deliver 3-4 times more radiation to tumor cell nuclei using the same targeting peptides, it could significantly improve treatment outcomes for patients with neuroendocrine cancers — and the antagonist peptide DOTA-LM3 may offer even greater benefit.","specificNumbers":"Compared 161Tb-DOTA-LM3 and 161Tb-DOTATATE against their 177Lu-labeled counterparts using CA20948 cell survival assays.","methodology":"In vitro study using CA20948 neuroendocrine tumor cells. Clonogenic survival assays compared cell killing by 161Tb vs 177Lu with both DOTATATE and DOTA-LM3 peptides. Cell binding, internalization, and dissociation measured over 7 days. Monte Carlo simulations computed separate S values for each particle emission type. Survival curves fitted to linear or linear-quadratic models.","limitations":"In vitro study using a single cell line — tumor heterogeneity and microenvironment effects are not captured. 161Tb is not yet widely available for clinical use. Monte Carlo simulations assumed spherical cells, which may oversimplify actual cell geometry. The study didn't account for bystander effects or DNA repair capacity differences between cell types."},{"rthcId":"RPEP-09314","title":"Evaluating Cardiovascular Benefits of Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RAs) in Type 2 Diabetes Mellitus: A Systematic Review.","authors":"Sreenivasan, Chithra; Parikh, Aneri; Francis, Aida J; Kanthajan, Tatchaya; Pandey, Manorama; AlQassab, Osamah; Nath, Tuheen Sankar","year":2024,"journal":"Cureus, 16(8), e66697","doi":"10.7759/cureus.66697","pmid":"39262558","tags":["glp-1-receptor-agonists","cardiovascular-health","type-2-diabetes","clinical-trials"],"studyType":"review","evidenceStrength":"strong","keyFinding":"GLP-1 RAs significantly reduce cardiovascular mortality, all-cause mortality, nonfatal MI, and nonfatal stroke in T2DM patients with existing cardiovascular risk factors. Limited data suggest possible protective effects against arrhythmias. Effects on heart failure hospitalization are minor. Benefits in patients without cardiovascular risk factors are uncertain.","whyItMatters":"Cardiovascular disease remains the leading cause of death in type 2 diabetes patients even with good glycemic control. This review consolidates the evidence that GLP-1 receptor agonists offer dual benefits — glucose lowering AND cardiovascular protection — strengthening the case for their earlier and broader use in diabetes management.","specificNumbers":"Review covers cardiovascular outcome trials showing reduced major adverse cardiovascular events (MACE) with GLP-1 RA treatment.","methodology":"Systematic review following 2020 PRISMA guidelines, searching PubMed, Google Scholar, Science Direct, and BioMed Central. 14 articles met inclusion criteria and underwent quality assessment. Outcomes evaluated included MACE, heart failure, stroke, all-cause mortality, and cardiovascular risk factor changes.","limitations":"Systematic review without meta-analysis (no pooled effect sizes). Most included trials were in high-cardiovascular-risk populations, limiting generalizability to lower-risk patients. Heterogeneity in GLP-1 RA types, doses, and follow-up durations across studies. Published in Cureus, a lower-impact journal. Did not assess individual GLP-1 RAs separately."},{"rthcId":"RPEP-09315","title":"Melanocortin 4 receptor mutation in obesity.","authors":"Sridhar, Gumpeny R; Gumpeny, Lakshmi","year":2024,"journal":"World journal of experimental medicine, 14(4), 99239","doi":"10.5493/wjem.v14.i4.99239","pmid":"39713072","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09316","title":"Efficacy and Safety of GLP-1 Agonists on Metabolic Parameters in Non-diabetic Patients with Inflammatory Bowel Disease.","authors":"St-Pierre, Joëlle; Klein, Jeremy; Choi, Natalie K; Fear, Evan; Pannain, Silvana; Rubin, David T","year":2024,"journal":"Digestive diseases and sciences, 69(12), 4437-4445","doi":"10.1007/s10620-024-08720-2","pmid":"39516435","tags":["glp-1-receptor-agonists","gut-health","weight-management"],"studyType":"cohort","evidenceStrength":"preliminary","keyFinding":"BMI decreased significantly from 34.0 to 31.0 (p<0.0001) with median weight loss of 8.15 kg (p<0.0001). CRP and ALT levels did not change significantly, suggesting no worsening of IBD inflammation. Total cholesterol and HbA1c showed trends toward improvement. Side effects: nausea (31%), constipation (25%).","whyItMatters":"IBD patients with obesity face unique challenges — their gut inflammation may interact with weight loss drugs in unpredictable ways, and concerns about GI side effects are amplified. This study provides the first evidence that GLP-1 agonists are both effective and apparently safe in IBD, filling an important clinical evidence gap.","specificNumbers":"Patients received semaglutide or liraglutide. The study tracked weight loss and metabolic parameters alongside IBD activity measures.","methodology":"Single-center observational cohort study of 36 adult IBD patients (non-diabetic) started on semaglutide or tirzepatide for weight loss between January 2021 and April 2024. Primary outcomes: BMI and total body weight changes. Secondary outcomes: tolerability, safety, metabolic risk factors.","limitations":"Very small sample (36 patients) from a single center. Observational design without a control group. Short follow-up period. Did not specifically assess IBD disease activity scores (only CRP). The study couldn't differentiate between semaglutide and tirzepatide effects. 86% of patients were already on advanced IBD therapy, which may have masked any inflammatory effects."},{"rthcId":"RPEP-09317","title":"Semaglutide decelerates the growth and progression of breast cancer by enhancing the acquired antitumor immunity.","authors":"Stanisavljevic, Isidora; Pavlovic, Sladjana; Simovic Markovic, Bojana; Jurisevic, Milena; Krajnovic, Tamara; Mijatovic, Sanja; Spasojevic, Marija; Mitrovic, Slobodanka; Corovic, Irfan; Jovanovic, Ivan","year":2024,"journal":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 181, 117668","doi":"10.1016/j.biopha.2024.117668","pmid":"39536536","tags":["glp-1-receptor-agonists","semaglutide","cancer-therapy","immune-system"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Semaglutide decelerated tumor appearance and growth in 4T1 breast cancer mice. No direct cytotoxic effect in vitro and no angiogenic effect. NK cell depletion did not affect tumor growth in treated mice. Semaglutide increased CD11c+ dendritic cell accumulation and maturation, decreased FoxP3+ regulatory T cells (in spleen and tumor), increased tumor-infiltrating T cells with anti-tumor phenotype, and enhanced CD8+ T cell cytotoxic capacity.","whyItMatters":"The finding that a widely-used GLP-1 drug enhances anti-tumor immunity is remarkable and has immediate clinical implications. With millions of patients taking semaglutide for diabetes and obesity, understanding its effects on cancer risk and progression is critical. This study suggests semaglutide may have cancer-protective effects through immunomodulation.","specificNumbers":"BALB/c mice with 4T1 breast cancer were treated intraperitoneally with semaglutide. The drug slowed both tumor appearance and growth.","methodology":"In vivo mouse study: 4T1 breast cancer cells implanted in BALB/c mice, treated with intraperitoneal semaglutide. In vitro cytotoxicity and angiogenesis assays. NK cell depletion experiments. Flow cytometry analysis of dendritic cells, regulatory T cells, and tumor-infiltrating T cells in spleen and primary tumor. In vitro CD8+ T cell cytotoxicity assays.","limitations":"Mouse breast cancer model (4T1) may not fully represent human breast cancer biology or immune responses. Intraperitoneal administration differs from standard subcutaneous dosing. The study didn't assess whether semaglutide's effects depend on weight loss or metabolic changes. Single tumor model — effects may vary across cancer types. No human data on anti-tumor immune effects of semaglutide."},{"rthcId":"RPEP-09318","title":"The impact of weight loss on fat-free mass, muscle, bone and hematopoiesis health: Implications for emerging pharmacotherapies aiming at fat reduction and lean mass preservation.","authors":"Stefanakis, Konstantinos; Kokkorakis, Michail; Mantzoros, Christos S","year":2024,"journal":"Metabolism: clinical and experimental, 161, 156057","doi":"10.1016/j.metabol.2024.156057","pmid":"39481534","tags":["glp-1-receptor-agonists","weight-management","muscle-and-bone","safety-and-side-effects"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Over 25% of total weight lost from both bariatric surgery and GLP-1 pharmacotherapy comes from fat-free mass. The myostatin-activin-follistatin system is crucial for lean mass preservation during negative energy balance. Bimagrumab, trevogrumab, and garetosmab inhibit activin/myostatin signaling and show promise in preventing muscle loss while promoting fat loss, either alone or combined with incretin receptor agonists.","whyItMatters":"As GLP-1 drugs become the standard for obesity treatment, the quality of weight loss — not just the quantity — becomes critical. Losing 25% or more of weight as muscle can accelerate aging, reduce metabolic rate, increase fall risk, and create a cycle of weight regain. Combining fat-targeting and muscle-preserving drugs could fundamentally improve obesity treatment outcomes.","specificNumbers":"Weight loss of 15-25% is common. Over 25% of weight lost is fat-free mass. Both surgical and pharmacological approaches show this pattern.","methodology":"Narrative review synthesizing evidence on body composition changes during weight loss (surgical and pharmacological), the biology of the myostatin-activin-follistatin system, and the clinical pipeline of muscle-preserving compounds for combination with anti-obesity medications.","limitations":"Narrative review format without systematic evidence assessment. Myostatin inhibitor clinical data is still limited — most are in early to mid-stage trials. Long-term safety of combined incretin + myostatin inhibitor therapy is unknown. The 25% fat-free mass loss figure varies significantly across studies and individual patients."},{"rthcId":"RPEP-09319","title":"Risk of major adverse cardiovascular events and all-cause mortality under treatment with GLP-1 RAs or the dual GIP/GLP-1 receptor agonist tirzepatide in overweight or obese adults without diabetes: a systematic review and meta-analysis.","authors":"Stefanou, Maria-Ioanna; Palaiodimou, Lina; Theodorou, Aikaterini; Safouris, Apostolos; Fischer, Urs; Kelly, Peter J; Dawson, Jesse; Katan, Mira; Katsanos, Aristeidis H; Lambadiari, Vaia; Giannopoulos, Sotirios; Alexandrov, Andrei V; Siasos, Gerasimos; Tsivgoulis, Georgios","year":2024,"journal":"Therapeutic advances in neurological disorders, 17, 17562864241281903","doi":"10.1177/17562864241281903","pmid":"39345822","tags":["glp-1-receptor-agonists","cardiovascular-health","weight-management","clinical-trials"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"GLP-1/GIP RAs vs placebo in non-diabetic overweight/obese adults: MACE reduced (OR 0.79, 95% CI 0.71-0.89), all-cause mortality reduced (OR 0.80, 95% CI 0.70-0.92), MI reduced (OR 0.72, 95% CI 0.61-0.86), nonfatal MI reduced (OR 0.72, 95% CI 0.61-0.85). Cardiovascular mortality trend (OR 0.84, 95% CI 0.71-1.01, p=0.06). No significant stroke reduction. No heterogeneity across studies (I²=0 for all outcomes).","whyItMatters":"Until now, the cardiovascular benefits of GLP-1 RAs were primarily demonstrated in diabetic populations. This meta-analysis proves that these drugs also protect hearts in non-diabetic obese people — a much larger population. This shifts the value proposition of GLP-1 drugs from 'diabetes medication with weight loss benefits' to 'cardiovascular protective therapy for anyone with obesity.'","specificNumbers":"Included liraglutide, semaglutide, and tirzepatide trials in non-diabetic overweight/obese populations.","methodology":"Systematic review and meta-analysis of 16 RCTs (13 GLP-1 RA trials, 3 tirzepatide trials) per PRISMA guidelines. Registered on PROSPERO (CRD42024515966). 28,168 overweight/obese adults without diabetes. Outcomes: MACE, all-cause and cardiovascular mortality, MI, and stroke. Pooled odds ratios with 95% CIs.","limitations":"Individual trial follow-up periods may be insufficient to fully capture cardiovascular events. Most participants likely had at least some cardiovascular risk factors beyond obesity. Stroke data are limited. The trend for CV mortality (p=0.06) needs confirmation with longer follow-up. Cost-effectiveness in non-diabetic populations hasn't been established."},{"rthcId":"RPEP-09320","title":"The GLP-1 receptor is expressed in vivo by human metastatic prostate cancer.","authors":"Stein, Mark S; Kalff, Victor; Williams, Scott G; Murphy, Declan G; Colman, Peter G; Hofman, Michael S","year":2024,"journal":"Endocrine oncology (Bristol, England), 4(1), e230015","doi":"10.1530/EO-23-0015","pmid":"38313829","tags":["glp-1-receptor-agonists","cancer-therapy"],"studyType":"cohort","evidenceStrength":"preliminary","keyFinding":"One of four patients with mCRPC had three bone metastases that were positive for both PSMA (confirming prostate cancer) and gallium-68-DOTA-exendin-4 (confirming GLP-1R expression). This is the first in vivo demonstration of GLP-1R expression in metastatic prostate cancer. The patient had six PSMA-avid lesions, three of which were also exendin-avid.","whyItMatters":"If prostate cancer expresses GLP-1 receptors, then the millions of men taking GLP-1 drugs for diabetes or obesity might already be receiving some anti-cancer benefit. It also opens the door to using GLP-1 receptor agonists as targeted cancer therapy or for GLP-1R-targeted imaging to guide treatment decisions in prostate cancer.","specificNumbers":"First study to confirm GLP-1R expression in metastatic castrate-resistant prostate cancer in human tissue specimens.","methodology":"Pilot imaging study. Men with mCRPC and multiple PSMA-avid PET/CT lesions underwent additional PET/CT with gallium-68-DOTA-exendin-4 (a GLP-1R-targeting radiotracer). Dual-positive lesions (PSMA+ and exendin+) confirmed in vivo GLP-1R expression by metastatic prostate cancer.","limitations":"Extremely small sample — only 4 patients were imaged, and 17 declined participation (the study offered no therapeutic benefit). Only 1 of 4 patients showed GLP-1R expression, and not all lesions in that patient were positive, suggesting heterogeneous expression. The GLP-1R-positive rate cannot be estimated from 4 patients. The radiotracer's sensitivity may be limited."},{"rthcId":"RPEP-09321","title":"Spleen Volume Reduction Is a Reliable and Independent Biomarker for Long-Term Risk of Leukopenia Development in Peptide Receptor Radionuclide Therapy.","authors":"Steinhelfer, Lisa; Jungmann, Friederike; Endrös, Lukas; Wenzel, Patrick; Haller, Bernhard; Nickel, Manuel; Haneder, Eva; Geisler, Fabian; Götze, Katharina; von Werder, Alexander; Eiber, Matthias; Makowski, Markus R; Braren, Rickmer; Lohöfer, Fabian","year":2024,"journal":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 65(8), 1244-1249","doi":"10.2967/jnumed.123.267098","pmid":"38991748","tags":["somatostatin-analogs","cancer-therapy","radionuclide-therapy","safety-and-side-effects"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"A 30% decline in spleen volume at 12 months post-177Lu-DOTATATE treatment predicted leukopenia at 24 months with AUC 0.91, sensitivity 93%, and specificity 90%. White blood cell counts and relative spleen volume reduction were also independent predictors, but spleen volume reduction was far superior. Automated splenic volume assessment outperformed all conventional laboratory parameters.","whyItMatters":"Leukopenia (low white blood cells) after PRRT is a serious complication that increases infection risk and may force treatment discontinuation. Currently, clinicians rely on blood tests that detect the problem only after it's developing. Spleen volume — measurable on routine CT scans already being performed for tumor monitoring — provides much earlier warning, allowing proactive management.","specificNumbers":"88 patients analyzed. Spleen volume reduction was identified as a reliable, independent biomarker for leukopenia risk.","methodology":"Retrospective analysis of 88 patients with metastatic neuroendocrine tumors treated with 177Lu-DOTATATE from February 2009 to July 2021. Inclusion: ≥4 treatment cycles, ≥24 months follow-up, tumor uptake ≥ liver on baseline receptor imaging. Blood counts and imaging data analyzed for predictive markers of radiation-induced leukopenia.","limitations":"Retrospective single-center study with moderate sample size. Exclusion of patients with <24 months follow-up and <4 treatment cycles may introduce survival bias. The optimal timing for spleen volume assessment and the generalizability to different treatment protocols need prospective validation. Automated splenic volumetry requires appropriate software."},{"rthcId":"RPEP-09322","title":"Glycaemic and weight effects of metabolic surgery or semaglutide in diabetes dosage for patients with type 2 diabetes.","authors":"Stenberg, Erik; Cao, Yang; Ottosson, Johan; Hedberg, Suzanne; Näslund, Erik","year":2024,"journal":"Diabetes, obesity & metabolism, 26(12), 5812-5818","doi":"10.1111/dom.15952","pmid":"39295084","tags":["glp-1-receptor-agonists","semaglutide","weight-management","type-2-diabetes"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"At 2 years: bariatric surgery achieved 26.4% ± 8.83% total weight loss vs 5.2% ± 7.87% with semaglutide (p<0.001). Mean HbA1c: 42.3 ± 11.18 after surgery vs 50.7 ± 12.48 after semaglutide (p<0.001). Complete diabetes remission: 63.0% with surgery vs 13.9% with semaglutide (p<0.001).","whyItMatters":"As semaglutide becomes the dominant medical weight loss treatment, patients and clinicians need realistic comparisons. This study provides the most direct head-to-head comparison available, showing that while semaglutide works, surgery remains substantially more effective for both weight loss and diabetes remission — an important consideration for treatment planning.","specificNumbers":"Patients treated for ≥2 years. Propensity score matching included age, sex, HbA1c, diabetes duration, and other factors.","methodology":"Propensity score-matched cohort study using the Scandinavian Obesity Surgery Registry and Swedish National Diabetes Registry. 606 surgical patients matched 1:1-2 with 997 semaglutide users starting treatment 2018-2020. Matching variables: age, sex, HbA1c, diabetes duration, insulin use, comorbidities, cancer history. Residual imbalances in GFR and BMI were statistically adjusted.","limitations":"Observational registry study — not a randomized trial. Despite propensity matching, residual confounding likely exists (surgical patients may be more motivated, have different baseline characteristics). Semaglutide doses used in 2018-2020 may have been lower than current protocols. The 5.2% weight loss with semaglutide is lower than seen in clinical trials, possibly reflecting real-world adherence issues. Surgery types varied (sleeve gastrectomy, Roux-en-Y, etc.). No data on adverse events or quality of life."},{"rthcId":"RPEP-09323","title":"The influence of neuropeptide Y (NPY) on the relationship between emotion regulation and mood-related pathology in survivors of childhood interpersonal trauma.","authors":"Stevens, Sarah K; Boley, Randy; Pollack, Mark; Hobfoll, Stevan; Shankman, Stewart; Pinkerton, Linzy; Valdespino-Hayden, Zerbrina; Glover, Angela C; Kaufman, Michelle; Dowd, Sheila; Zalta, Alyson K","year":2024,"journal":"Journal of affective disorders, 362, 258-262","doi":"10.1016/j.jad.2024.07.009","pmid":"38971192","tags":["neuropeptides","mental-health","stress-response"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Difficulties in emotion regulation significantly predicted psychopathology (B=0.032, p<0.01). This relationship was significantly moderated by NPY levels (B=-0.001, p<0.05) — higher NPY weakened the emotion-regulation-to-psychopathology link. The overall model was significant (R²=0.26, F(5,48)=3.46, p<0.01).","whyItMatters":"Understanding why some trauma survivors develop mental illness while others are resilient is crucial for prevention and treatment. This study identifies NPY as a biological resilience mechanism that specifically buffers the impact of emotional dysregulation — potentially opening the door to NPY-based interventions that enhance resilience in at-risk populations.","specificNumbers":"NPY is a 36-amino acid peptide widely expressed in the limbic system. Study focused on adult survivors of childhood interpersonal trauma.","methodology":"Cross-sectional moderated multiple regression analysis. 54 adults exposed to childhood interpersonal criterion A trauma recruited from an urban medical center. Plasma NPY levels measured from blood samples. Self-report measures of emotion regulation difficulties and mood-related psychopathology. Part of a larger clinical trial (NCT02279290).","limitations":"Small sample size (n=54) limits statistical power and generalizability. Cross-sectional design cannot establish causation. Plasma NPY may not accurately reflect brain NPY concentrations. Self-report measures of emotion regulation have known limitations."},{"rthcId":"RPEP-09324","title":"Plasma Protein Biomarkers and Long-Term Cardiovascular Mortality Risk in Patients With Chronic Coronary Heart Disease.","authors":"Stewart, Ralph A H; Robledo, Kristy P; Tonkin, Andrew M; Keech, Anthony; Kritharides, Leonard; Marschner, Ian; Janus, Edward; Thompson, Peter L; Watts, Gerald F; Zeller, Tanja; White, Harvey D; Simes, John","year":2024,"journal":"Journal of the American Heart Association, 13(21), e034367","doi":"10.1161/JAHA.123.034367","pmid":"39450716","tags":["natriuretic-peptides","cardiovascular-health","diagnostics"],"studyType":"cohort","evidenceStrength":"strong","keyFinding":"All 6 biomarkers — BNP, troponin I, cystatin-C, CRP, D-dimer, and midregional proadrenomedullin — were significantly associated with cardiovascular death (n=1,903) both during the randomized trial period and for 10 additional years after trial completion (each p<0.001). Associations were sustained for at least 15 years total.","whyItMatters":"Most biomarker studies only assess short-term prediction. Finding that peptide biomarkers like BNP and proadrenomedullin remain predictive for 15+ years suggests they capture deep, stable aspects of cardiovascular disease that don't fluctuate quickly. This has implications for long-term risk stratification and treatment decisions in coronary heart disease patients.","specificNumbers":"7,745 patients from the LIPID trial. Biomarkers measured: BNP, troponin I, cystatin-C, and C-reactive protein.","methodology":"Cohort study of 7,745 patients from the LIPID trial (Long-Term Intervention with Pravastatin in Ischemic Disease). Biomarkers measured at baseline and 1 year. Landmark analyses from 1 year evaluated discrimination for cardiovascular death during the next 5 years of the trial and 10 additional years of follow-up.","limitations":"The LIPID trial enrolled patients in the 1990s, and cardiovascular management has evolved significantly since then. Biomarker associations may differ with modern treatments. The study didn't assess whether serial measurements improve prediction over single measurements. Observational analysis from a statin trial — cannot establish whether biomarker-guided treatment improves outcomes."},{"rthcId":"RPEP-09325","title":"Cyclic adenosine monophosphate critically modulates cardiac GLP-1 receptor's anti-inflammatory effects.","authors":"Stoicovy, Renee A; Cora, Natalie; Perez, Arianna; Nagliya, Deepika; Del Calvo, Giselle; Lopez, Teresa Baggio; Weinstein, Emma C; Borges, Jordana I; Maning, Jennifer; Lymperopoulos, Anastasios","year":2024,"journal":"Inflammation research : official journal of the European Histamine Research Society ... [et al.], 73(11), 2043-2056","doi":"10.1007/s00011-024-01950-0","pmid":"39305297","tags":["glp-1-receptor-agonists","cardiovascular-health","inflammation"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Liraglutide dose-dependently inhibited LPS-induced apoptosis and inflammation in cardiac cells via GLP-1R-mediated cAMP production. AC inhibition completely abolished liraglutide's anti-inflammatory effects. Roflumilast (PDE4 inhibitor) enhanced cAMP production and amplified liraglutide's protection. Both PKA and Epac pathways are required — inhibiting either alone only partially blocked effects, but inhibiting both fully prevented liraglutide's anti-inflammatory action.","whyItMatters":"Understanding exactly how GLP-1 drugs protect the heart is crucial for optimizing their cardiovascular benefits. This study shows that cAMP is the essential mediator and identifies PDE4 inhibitors as potential combination partners. Since PDE4 inhibitors (like roflumilast, already approved for COPD) are available, this combination strategy could be tested clinically.","specificNumbers":"GLP-1R couples to Gs proteins to activate adenylyl cyclase, raising cAMP levels that mediate both anti-apoptotic and anti-inflammatory effects.","methodology":"In vitro mechanistic study using H9c2 cardiac cells. LPS-induced inflammatory injury model. Pharmacological inhibition of adenylyl cyclase, PKA, Epac1/2, and PDE4/PDE8. GLP-1R specificity confirmed with exendin(9-39) antagonist. Measured: cytokines (TNF-α, IL-1β, IL-6), iNOS, NF-κB activity, MMP-2/9, apoptosis, and myocardial injury markers.","limitations":"In vitro study using a rat cardiac cell line (H9c2), not primary human cardiomyocytes. LPS-induced inflammation is a simplified model of cardiac inflammation. PDE4 inhibitors have systemic effects (nausea, diarrhea) that may limit combination use. The study didn't assess whether these mechanisms operate identically in vivo."},{"rthcId":"RPEP-09326","title":"Semaglutide Improves Myocardial Perfusion and Performance in a Large Animal Model of Coronary Artery Disease.","authors":"Stone, Christopher R; Harris, Dwight D; Broadwin, Mark; Kanuparthy, Meghamsh; Nho, Ju-Woo; Yalamanchili, Keertana; Hamze, Jad; Abid, M Ruhul; Sellke, Frank W","year":2024,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2024.08.15.608191","pmid":"39211263","tags":["glp-1-receptor-agonists","semaglutide","cardiovascular-health"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Semaglutide improved left ventricular ejection fraction at rest and during rapid pacing (both p<0.03), increased perfusion to the most ischemic myocardium at rest and during pacing (both p<0.03), reduced perivascular and interstitial fibrosis (both p<0.03), and decreased apoptosis (p=0.008). Mechanism: increased AMPK activation (p=0.005) with downstream eNOS upregulation (p=0.014).","whyItMatters":"This is the first study showing oral semaglutide directly improves heart function in coronary artery disease — in a large animal model without diabetes or obesity. It suggests semaglutide's cardiovascular benefits aren't just from metabolic improvement but from direct cardiac effects, potentially offering hope for patients with refractory angina who have no other options.","specificNumbers":"Coronary artery disease is the leading cause of death worldwide. Up to 1/3 of patients have residual angina despite optimal therapy.","methodology":"Randomized controlled animal study. 17 Yorkshire swine received ameroid constrictors on the left circumflex coronary artery. Treatment group (n=8): oral semaglutide 1.5→3 mg over 5 weeks. Control group (n=9): no drug. Cardiac function measured by pressure-volume loop catheterization, perfusion by microsphere injection. Tissue analysis by immunoblotting, immunohistochemistry, and immunofluorescence.","limitations":"Preprint (bioRxiv) — not yet peer reviewed. Relatively small group sizes (8-9 per group). Short treatment duration (5 weeks). Ameroid constrictor model creates gradual stenosis that may not fully replicate human coronary disease. Oral semaglutide doses may not be directly comparable to human doses. No long-term follow-up data."},{"rthcId":"RPEP-09327","title":"Tirzepatide Improves Early Dumping Syndrome and Glucose Nadir in Postbariatric Hypoglycemia After Sleeve Gastrectomy.","authors":"Stortz, Ethan; Lawler, Helen","year":2024,"journal":"JCEM case reports, 2(11), luae194","doi":"10.1210/jcemcr/luae194","pmid":"39444516","tags":["glp-1-receptor-agonists","weight-management","safety-and-side-effects"],"studyType":"case series","evidenceStrength":"preliminary","keyFinding":"Tirzepatide 2.5 mg weekly decreased postprandial glucose peaks, increased postprandial glucose nadirs (preventing dangerous hypoglycemia), improved time in range on CGM, and resolved postprandial bloating and diarrhea from dumping syndrome. First reported use of a dual-incretin agonist for either dumping syndrome or postbariatric hypoglycemia.","whyItMatters":"Dumping syndrome and postbariatric hypoglycemia are frustrating complications of bariatric surgery with limited treatment options. GLP-1 agonists alone have shown mixed results for these conditions. Tirzepatide's dual GIP/GLP-1 mechanism may offer superior glucose stabilization and symptom control, potentially providing a new treatment option for these challenging post-surgical conditions.","specificNumbers":"Patient: 46-year-old woman. Tirzepatide dose: 2.5 mg weekly. Improvements tracked via continuous glucose monitoring (CGM).","methodology":"Single case report of a 46-year-old woman with prediabetes and obesity post-sleeve gastrectomy presenting with dumping syndrome and postbariatric hypoglycemia. Monitored with continuous glucose monitoring (CGM) before and during tirzepatide treatment.","limitations":"Single case report — the lowest level of evidence. Impossible to generalize from one patient. The dose was very low (2.5 mg), and whether the effects persist or require dose escalation is unknown. No control comparison. The patient had sleeve gastrectomy specifically; effects may differ for other bariatric procedures."},{"rthcId":"RPEP-09328","title":"New Insights on Using Oral Semaglutide versus Dapagliflozin in Patients with Type 2 Diabetes and Metabolic Dysfunction-Associated Steatotic Liver Disease.","authors":"Stratina, Ermina; Stanciu, Carol; Nastasa, Robert; Zenovia, Sebastian; Stafie, Remus; Rotaru, Adrian; Cuciureanu, Tudor; Muzica, Cristina; Sfarti, Catalin; Girleanu, Irina; Minea, Horia; Petrea, Oana; Huiban, Laura; Chiriac, Stefan; Singeap, Ana-Maria; Vlad, Oana; Cojocariu, Camelia; Trifan, Anca","year":2024,"journal":"Diagnostics (Basel, Switzerland), 14(14)","doi":"10.3390/diagnostics14141475","pmid":"39061612","tags":["glp-1-receptor-agonists","semaglutide","liver-health","type-2-diabetes"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Oral semaglutide significantly reduced liver stiffness (8.07 ± 2.90 → 6.51 ± 3.09 kPa, p<0.001) measured by VCTE at 6 months. Both groups showed reduced BMI, waist circumference, and waist-to-hip ratio. Semaglutide showed notable HbA1c decrease (p-value referenced). Both were add-on to metformin.","whyItMatters":"Fatty liver disease affects up to 70% of type 2 diabetes patients and is a growing cause of liver transplantation. Finding that oral semaglutide significantly reduces liver stiffness — a marker of fibrosis progression — provides evidence for choosing GLP-1 agonists over SGLT2 inhibitors when liver health is a clinical priority.","specificNumbers":"Comparison focused on patients with both T2DM and MASLD/MASH. MASLD is associated with cirrhosis and hepatocellular carcinoma risk.","methodology":"Prospective cohort study of 187 patients with T2DM at a single center. 95 patients received oral semaglutide and 92 received dapagliflozin, both added to metformin. Liver assessment by vibration-controlled transient elastography (VCTE) for steatosis and fibrosis at baseline and 6 months. Anthropometric and metabolic parameters measured.","limitations":"Non-randomized design with potential selection bias between treatment groups. Single center in Romania may limit generalizability. 6-month follow-up is relatively short for assessing liver outcomes. VCTE is an indirect measure of fibrosis — liver biopsy remains the gold standard. The abstract mentions a significant p-value for HbA1c but doesn't clearly report the value."},{"rthcId":"RPEP-09329","title":"The Effect of Retinoic Acid on Neutrophil Innate Immune Interactions With Cutaneous Bacterial Pathogens.","authors":"Stream, Alexandra; Corriden, Ross; Döhrmann, Simon; Gallo, Richard L; Nizet, Victor; Anderson, Ericka L","year":2024,"journal":"Infectious microbes & diseases, 6(2), 65-73","doi":"10.1097/im9.0000000000000145","pmid":"38952747","tags":["antimicrobial-peptides","immune-system","skin-health"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Retinoic acid stimulated human neutrophils to produce LL-37 antimicrobial peptide, reactive oxygen species, and extracellular traps, enhancing MRSA killing in vitro. RA directly inhibited GAS growth and, in a murine skin infection model, topical RA reduced both skin lesion size and bacterial burden.","whyItMatters":"Antimicrobial resistance is a growing crisis, and this research suggests vitamin A derivatives could enhance the body's natural antimicrobial peptide defenses. The finding that retinoic acid boosts cathelicidin (LL-37) production — a key human antimicrobial peptide — while also directly killing certain bacteria opens a potential dual-action therapeutic approach for drug-resistant skin infections.","specificNumbers":"RA boosted neutrophil killing of methicillin-resistant bacteria. Effects on antimicrobial peptide production were characterized.","methodology":"In vitro experiments using primary human neutrophils treated with retinoic acid, tested against MRSA, E. coli K1, P. aeruginosa, and GAS. Antimicrobial peptide production (LL-37), ROS, and NETs were measured. In vivo murine skin infection models tested topical RA against both MRSA and GAS.","limitations":"In vitro and animal study with no human clinical data. RA failed to reduce MRSA burden in vivo despite in vitro activity, suggesting the in vitro-to-in vivo translation is not straightforward. GAS-specific effects may not generalize to other pathogens. Murine skin immunity differs from human skin immunity."},{"rthcId":"RPEP-09330","title":"Angiogenic biomarkers of response to treatment with peptide receptor radionuclide therapy in neuroendocrine tumours.","authors":"Strzelczyk, Janusz; Wójcik-Giertuga, Monika; Makulik, Karolina; Rosiek, Violetta; Kamiński, Grzegorz; Kajdaniuk, Dariusz; Kos-Kudła, Beata","year":2024,"journal":"Endokrynologia Polska, 75(4), 412-418","doi":"10.5603/ep.100241","pmid":"39279310","tags":["somatostatin-analogs","cancer-therapy","radionuclide-therapy","diagnostics"],"studyType":"cohort","evidenceStrength":"preliminary","keyFinding":"After four PRRT cycles in 40 NET patients, CgA, VEGF-R1, and VEGF-R2 decreased significantly while VEGF-R3 increased. VEGF levels were unchanged. VEGF-R1 had the best discriminatory value for treatment response (AUC 0.7).","whyItMatters":"PRRT uses radiolabeled somatostatin peptide analogs to target tumors, but predicting which patients will respond remains challenging. Identifying reliable blood biomarkers like VEGF-R1 could help clinicians monitor treatment effectiveness and potentially guide therapy decisions without waiting for imaging results.","specificNumbers":"NETs are characterized by rich vascularization. PRRT uses radiolabeled peptides targeting somatostatin receptors.","methodology":"Prospective cohort of 40 patients with gastro-entero-pancreatic and broncho-pulmonary neuroendocrine tumors who completed four cycles of PRRT. Serum CgA, VEGF, VEGF-R1, VEGF-R2, and VEGF-R3 measured by ELISA before and after treatment. AUROC analysis assessed biomarker discriminatory ability for treatment response.","limitations":"Small sample size (40 patients) limits statistical power and generalizability. Single-center study. AUC of 0.7 indicates only moderate discriminatory ability. No comparison to imaging-based response assessment. Mixed GEP and BP NET types may mask tumor-specific biomarker patterns."},{"rthcId":"RPEP-09331","title":"In vitro pharmacological characterization of growth hormone secretagogue receptor ligands using the dynamic mass redistribution and calcium mobilization assays.","authors":"Sturaro, Chiara; Ruzza, Chiara; Ferrari, Federica; Pola, Pietro; Argentieri, Michela; Frezza, Alessia; Marzola, Erika; Bettegazzi, Barbara; Cattaneo, Stefano; Pietra, Claudio; Malfacini, Davide; Calò, Girolamo","year":2024,"journal":"European journal of pharmacology, 981, 176880","doi":"10.1016/j.ejphar.2024.176880","pmid":"39128804","tags":["ghrelin","appetite-and-metabolism","drug-delivery"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Ghrelin, anamorelin, HM01, and HM03 behaved as potent full GHSR agonists in both assays. LEAP2(1-14) was identified as a GHSR inverse agonist in DMR but not calcium assays. PF-05190457, HM04, and H1498 acted as inverse agonists in DMR but only antagonists in calcium mobilization, demonstrating DMR's superior ability to discriminate receptor pharmacology.","whyItMatters":"Understanding the precise pharmacology of ghrelin receptor ligands is critical for developing drugs targeting appetite, cachexia, metabolic disorders, and addiction. This study provides the most comprehensive comparison of GHSR ligands to date and introduces a superior assay method for distinguishing different types of receptor modulation.","specificNumbers":"Characterized multiple GHSR ligand types: agonists, antagonists, and inverse agonists using the DMR assay.","methodology":"In vitro pharmacological characterization using CHO cells expressing human GHSR. Two parallel assays: label-free dynamic mass redistribution (DMR) and calcium mobilization. Tested endogenous peptides (ghrelin, desacyl-ghrelin, LEAP2) and synthetic ligands (anamorelin, HM01, HM03, HM04, YIL-781, PF-05190457, R011, H1498).","limitations":"Entirely in vitro using a single cell line (CHO-GHSR). Pharmacological profiles in recombinant systems may not fully reflect in vivo receptor behavior. No functional outcome data (appetite, GH release) assessed. Patent literature compounds have limited published characterization."},{"rthcId":"RPEP-09332","title":"Management of pasireotide-induced hyperglycemia in patients with acromegaly: An experts' consensus statement.","authors":"Störmann, Sylvère; Meyhöfer, Sebastian M; Groener, Jan B; Faust, Johanna; Schilbach, Katharina; Seufert, Jochen; Vergès, Bruno","year":2024,"journal":"Frontiers in endocrinology, 15, 1348990","doi":"10.3389/fendo.2024.1348990","pmid":"38405148","tags":["somatostatin-analogs","hormones-and-signaling","safety-and-side-effects"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Pasireotide-induced hyperglycemia is pathophysiologically distinct — caused by decreased GIP and GLP-1 secretion, not insulin resistance. Incretin-based therapeutics (DPP-4 inhibitors and GLP-1 RAs) are recommended as alternatives to metformin monotherapy because they target the specific mechanism. Patient risk stratification and monitoring protocols are proposed.","whyItMatters":"Hyperglycemia limits pasireotide use and can force patients off an otherwise effective acromegaly treatment. Understanding that the mechanism involves incretin suppression — and therefore responding with incretin-based therapies — is more rational than default metformin use and could allow more patients to remain on pasireotide safely.","specificNumbers":"Pasireotide is a second-line treatment for acromegaly when first-line somatostatin analogues fail. Hyperglycemia is the major dose-limiting side effect.","methodology":"Expert consensus statement based on review of available evidence on pasireotide-induced hyperglycemia pathophysiology and management. Developed by a panel of endocrinologists with expertise in acromegaly and diabetes management.","limitations":"Consensus statement, not a systematic review or clinical trial. Limited by the small amount of published evidence specifically comparing different hyperglycemia management strategies during pasireotide treatment. Expert opinion may be influenced by individual experience and potential conflicts of interest."},{"rthcId":"RPEP-09333","title":"Preparation, identification, and molecular docking of novel angiotensin-converting enzyme inhibitory peptides derived from rice-based distillers' spent cakes.","authors":"Su, Hanxing; Fan, Wenlai; Xu, Yan; Tang, Shaopei; Yue, Dehong; Liao, Zuyue","year":2024,"journal":"Journal of the science of food and agriculture, 104(11), 6506-6517","doi":"10.1002/jsfa.13474","pmid":"38507298","tags":["bioactive-peptides","cardiovascular-health"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Four novel ACE-inhibitory peptides from RDSC hydrolysates showed IC50 values of 11.63, 12.34, 19.55, and 33.54 μmol/L. Molecular docking identified key residues (Glu123, Asp121, Arg522, Lys118) at both active and inactive ACE sites that enhance inhibitory activity.","whyItMatters":"ACE inhibitors are a cornerstone of hypertension treatment but synthetic versions can cause side effects like dry cough. Food-derived ACE-inhibitory peptides represent a potentially safer, natural alternative. Identifying potent peptides from industrial waste also adds value to agricultural byproducts.","specificNumbers":"Alcalase hydrolysis for 4 hours was used. Multiple ACE-inhibitory peptides identified and characterized by molecular docking.","methodology":"In vitro study: alcalase hydrolysis of RDSC for 4 hours, ultrafiltration to isolate low-molecular-weight fractions, followed by chromatographic purification and LC-MS/MS peptide identification. ACE inhibition measured in vitro. Molecular docking performed to analyze binding interactions.","limitations":"Entirely in vitro — no evidence these peptides survive digestion, cross the intestinal barrier, or lower blood pressure in living organisms. IC50 values were measured in a test tube, which may not reflect in vivo potency. Molecular docking is computational prediction, not experimental proof of binding."},{"rthcId":"RPEP-09334","title":"A high hydrophobic moment arginine-rich peptide screened by a machine learning algorithm enhanced ADC antitumor activity.","authors":"Su, Ruo-Long; Cao, Xue-Wei; Zhao, Jian; Wang, Fu-Jun","year":2024,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 30(12), e3628","doi":"10.1002/psc.3628","pmid":"38950972","tags":["cell-penetrating-peptides","cancer-therapy","drug-delivery"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"NCR peptide delivered >4x more EGFP into cells than TAT peptide and accumulated in lysosomes. Domain Z-NCR vector non-covalently bound T-DM1 and significantly enhanced its cytotoxicity against HER2-positive tumor cells (MTT assay) while maintaining drug specificity for HER2-expressing cells.","whyItMatters":"Antibody-drug conjugates like T-DM1 (trastuzumab emtansine) are important cancer therapies but their effectiveness is limited by inefficient cellular uptake and lysosomal delivery. This peptide-based enhancement strategy could improve ADC potency without changing the drug itself, potentially allowing lower doses or overcoming resistance.","specificNumbers":"NCR was derived from the Rev protein of caprine arthritis-encephalitis virus. Screened from nuclear localization/export signal databases.","methodology":"In vitro study: MLCPP2.0 machine learning algorithm screened nuclear localization/export signal databases for CPP candidates. Cell-penetrating activity verified by fluorescent tracing. NCR fused to domain Z (IgG Fc-binding) to create T-DM1 delivery vector. Cytotoxicity assessed by MTT assay in HER2-positive tumor cells.","limitations":"In vitro only — no animal tumor models or pharmacokinetic data. The domain Z-NCR vector binds non-covalently, which may be unstable in blood. Only tested with T-DM1 against HER2-positive cells; generalizability to other ADCs unknown. No toxicity or immunogenicity assessment."},{"rthcId":"RPEP-09335","title":"Cell-penetrating peptides TAT and 8R functionalize P22 virus-like particles to enhance tissue distribution and retention in vivo.","authors":"Su, Shibo; Shen, Xuegang; Shi, Xinqi; Li, Xin; Chen, Jin; Yang, Wei; Sun, Mingxia; Tang, Yan-Dong; Wang, Haiwei; Wang, Shujie; Cai, Xuehui; Lu, Yu; An, Tongqing; Yang, Yongbo; Meng, Fandan","year":2024,"journal":"Frontiers in veterinary science, 11, 1460973","doi":"10.3389/fvets.2024.1460973","pmid":"39290505","tags":["cell-penetrating-peptides","drug-delivery","peptide-vaccines"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Both TAT and 8R CPPs significantly enhanced P22 VLP cellular uptake in vitro and tissue accumulation in vivo. At 24 hours post-injection, TAT-conjugated VLPs showed superior lung distribution and retention, while 8R-conjugated VLPs showed better brain accumulation. TAT was overall superior for cellular uptake and tissue accumulation.","whyItMatters":"Targeted drug delivery remains a major challenge in medicine. This study demonstrates that different cell-penetrating peptides can direct the same nanoparticle platform to different tissues — TAT to lungs, 8R to brain — opening possibilities for tissue-specific drug delivery using a modular peptide-based targeting approach.","specificNumbers":"Two CPPs tested: TAT and 8R. P22 VLP platform used as delivery vehicle. Tissue-specific distribution patterns observed.","methodology":"In vitro and in vivo study: P22 VLP self-assembled particles prepared using a prokaryotic expression system with TAT- or 8R-conjugated mCherry on the capsid protein. Cellular uptake measured by fluorescence in vitro. Tissue distribution and retention assessed in animal models at multiple time points post-injection.","limitations":"Animal study with no human data. Tissue distribution was assessed using fluorescent reporter, not actual therapeutic cargo. Long-term retention and potential immunogenicity of VLP-CPP constructs not evaluated. The mechanism underlying differential tissue targeting of TAT vs 8R is not fully explained."},{"rthcId":"RPEP-09336","title":"It Takes Two to Tangle: Microneedle Patches Co-delivering Monoclonal Antibodies and Engineered Antimicrobial Peptides Effectively Eradicate Wound Biofilms.","authors":"Su, Yajuan; Shahriar, Shatil S M; Andrabi, Syed Muntazir; Wang, Chenlong; Sharma, Navatha Shree; Xiao, Yizhu; Wong, Shannon L; Wang, Guangshun; Xie, Jingwei","year":2024,"journal":"Macromolecular bioscience, 24(5), e2300519","doi":"10.1002/mabi.202300519","pmid":"38217528","tags":["antimicrobial-peptides","wound-healing","drug-delivery"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"W379 + anti-PBP2a co-loaded microneedle patches reduced bacteria from ~3.31×10⁷ to 1.28×10² CFU/mL in 2 hours in vitro. Ex vivo: ~7.18 log CFU reduction after one application within 48 hours. In vivo (diabetic mouse): bacterial colonies undetectable after two treatments within 48 hours. No evident cytotoxicity.","whyItMatters":"Wound biofilms affect an estimated 60-80% of chronic wounds and are a leading cause of non-healing. Current treatments are limited. This dual-action approach — combining an antimicrobial peptide with a targeted antibody in a painless microneedle delivery system — represents a genuinely novel strategy that could transform wound care, especially for diabetic patients.","specificNumbers":"Bacterial count reduced from ~3.31×10⁷ to 1.28×10² CFU/mL within 2 hours. Combination: 250 ng/mL W379 + 250 ng/mL anti-PBP2a.","methodology":"In vitro, ex vivo, and in vivo study: dissolvable PVP microneedle patches loaded with engineered antimicrobial peptide W379 (250 ng/mL) and anti-PBP2a monoclonal antibody (250 ng/mL). Tested individually and in combination. In vivo testing used a type II diabetic mouse wound biofilm model.","limitations":"Small-scale animal study — needs to be validated in larger animals and humans. The diabetic mouse wound model doesn't fully replicate human chronic wound complexity. Long-term wound healing outcomes not assessed. Only tested against one bacterial strain. Cost and scalability of manufacturing dual-loaded microneedle patches not addressed."},{"rthcId":"RPEP-09337","title":"Association between glucagon-like peptide-1 receptor agonists use and change in alcohol consumption: a systematic review.","authors":"Subhani, Mohsan; Dhanda, Ashwin; King, James A; Warren, Fiona C; Creanor, Siobhan; Davies, Melanie J; Eldeghaidy, Sally; Bawden, Stephen; Gowland, Penny A; Bataller, Ramon; Greenwood, Justin; Kaar, Stephen; Bhala, Neeraj; Aithal, Guruprasad P","year":2024,"journal":"EClinicalMedicine, 78, 102920","doi":"10.1016/j.eclinm.2024.102920","pmid":"39764544","tags":["glp-1-receptor-agonists","mental-health","addiction"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Exenatide RCT: no significant reduction in heavy drinking days vs placebo overall (95% CI -7.4 to 19.4, p=0.37), but fMRI showed reduced brain reward center cue reactivity in obese subgroup. Dulaglutide secondary analysis: 29% more likely to reduce alcohol intake (relative effect 0.71, CI 0.52-0.97, p=0.04). Observational studies showed fewer alcohol-related healthcare events with GLP-1 RAs.","whyItMatters":"Alcohol-related mortality is rising despite available treatments. The unexpected finding that diabetes/obesity drugs might reduce alcohol consumption has generated enormous public interest. This review provides the first comprehensive assessment of the clinical evidence, separating signal from hype.","specificNumbers":"Searched multiple databases through August 2024. Included preclinical, observational, and clinical trial data.","methodology":"Systematic review searching Ovid Medline, EMBASE, PsycINFO, ClinicalTrials.gov, and ProQuest through August 2024. Included 6 studies (88,190 total participants): 2 RCTs (286 participants) and 4 observational studies. Registered with PROSPERO. Assessed alcohol consumption changes, alcohol-related events, healthcare utilization, and fMRI cue reactivity.","limitations":"Only 286 participants in RCTs — the vast majority (87,904) were from observational studies with inherent confounding. The exenatide RCT was not powered for alcohol as a primary outcome. Heterogeneous study designs, populations, and GLP-1 RA types make synthesis difficult. Publication bias possible in this high-interest area."},{"rthcId":"RPEP-09338","title":"Peptide-based therapeutics targeting genetic disorders.","authors":"Subramanian, Shweta; Jain, Meenakshi; Misra, Rajkumar; Jain, Rahul","year":2024,"journal":"Drug discovery today, 29(12), 104209","doi":"10.1016/j.drudis.2024.104209","pmid":"39419376","tags":[],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Peptides are emerging as versatile tools for treating genetic disorders through multiple mechanisms beyond just acting as drugs. The review identifies three key roles for peptides in this space:\n\n1. **Direct therapeutics**: A limited but growing number of peptide-based drugs treat genetic disorders, with several more in clinical trials. Most current therapies provide symptomatic relief rather than addressing the underlying genetic defect.\n2. **Gene delivery carriers**: Peptides can serve as vehicles to deliver gene therapy payloads (corrective DNA or RNA) to target cells, overcoming delivery challenges that have limited gene therapy.\n3. **Diagnostic tools**: Peptide-based biomarkers can detect specific mutations, and peptide vaccines are being explored as treatments for certain genetic conditions.\n\nThe review maps the mechanistic underpinnings of various genetic disorders and identifies where peptide-based approaches could be most beneficial.","whyItMatters":"Genetic disorders affect millions of people worldwide with limited treatment options — most therapies only manage symptoms. The peptide field has largely focused on metabolic, cardiovascular, and oncology indications, but this review highlights an underexplored frontier: using peptide versatility (as drugs, carriers, and diagnostics) to address genetic diseases. As gene therapy advances, peptide-based delivery systems could solve the critical 'last mile' delivery problem that has limited many gene therapies.","specificNumbers":"Limited number of approved peptide drugs for GDs · Several candidates in clinical trials · 3 peptide roles: therapeutics, gene carriers, diagnostics · Multiple genetic disorder mechanisms reviewed","methodology":"This is a narrative review published in Drug Discovery Today that surveys the landscape of peptide-based approaches to genetic disorders. The authors examine the underlying biology of various genetic diseases, current peptide drugs and clinical candidates, and emerging applications of peptides as gene delivery vehicles and diagnostic tools.","limitations":"As a narrative review, it doesn't use systematic methodology or quantitatively assess evidence. The peptide-based genetic disorder space is relatively early-stage, so much of the review covers preclinical and conceptual work rather than proven therapies. The breadth of genetic disorders covered means depth on any single condition is limited."},{"rthcId":"RPEP-09339","title":"Substance P promotes transforming growth factor-β-induced collagen synthesis in human corneal fibroblasts.","authors":"Sugioka, Koji; Nishida, Teruo; Murakami, Junko; Itahashi, Motoki; Yunoki, Mai; Kusaka, Shunji","year":2024,"journal":"American journal of physiology. Cell physiology, 326(5), C1482-C1493","doi":"10.1152/ajpcell.00084.2024","pmid":"38525537","tags":["neuropeptides","wound-healing","collagen-peptides"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Substance P had no independent effect on corneal fibroblast collagen synthesis or MMP-1 expression. However, it significantly enhanced TGF-β-induced collagen type I synthesis. This effect was mediated by p38 MAPK activation and was blocked by neurokinin-1 receptor inhibition. SP did not affect IL-1β-stimulated MMP-1 expression.","whyItMatters":"Neurotrophic keratopathy affects people after eye surgery, herpes infections, or diabetes-related nerve damage. Understanding that substance P amplifies wound healing signals provides a molecular explanation for why denervated corneas heal poorly and points toward potential therapeutic strategies using neuropeptide supplementation.","specificNumbers":"Substance P enhanced TGF-β-induced collagen synthesis. The cornea is densely innervated with sensory nerve fibers.","methodology":"In vitro study using cultured human corneal fibroblasts. Collagen type I synthesis measured with and without substance P, TGF-β, and IL-1β. p38 MAPK activation assessed by phosphorylation assays. Pharmacological inhibition of p38 MAPK and neurokinin-1 receptor used to confirm signaling pathway.","limitations":"In vitro study using isolated fibroblasts — doesn't capture the complex corneal wound healing environment with multiple cell types, tear film factors, and immune cells. Only one neuropeptide (substance P) tested. No animal model or clinical validation of the proposed mechanism."},{"rthcId":"RPEP-09340","title":"Bacteriocin diversity, function, discovery and application as antimicrobials.","authors":"Sugrue, Ivan; Ross, R Paul; Hill, Colin","year":2024,"journal":"Nature reviews. Microbiology, 22(9), 556-571","doi":"10.1038/s41579-024-01045-x","pmid":"38730101","tags":[],"studyType":"Review","evidenceStrength":"strong","keyFinding":"Bacteriocins are a diverse class of antimicrobial peptides produced by bacteria that show strong potential as alternatives to conventional antibiotics. Despite nearly a century of research, no bacteriocin has been approved for therapeutic use in humans — they remain limited to food preservation applications like nisin.\n\nThe review catalogs the broad structural diversity of bacteriocins, from simple linear peptides to extensively post-translationally modified structures. Their mechanisms of action include membrane disruption, pore formation, and inhibition of cell wall synthesis. Crucially, many bacteriocins have narrow-spectrum activity, meaning they can target specific pathogens while leaving beneficial gut bacteria intact — a major advantage over broad-spectrum antibiotics.\n\nModern tools including metagenomic mining and bioengineering are accelerating the discovery and optimization of novel bacteriocins, but translation from lab to clinic has been stalled by challenges in formulation, stability, and regulatory pathways.","whyItMatters":"With antimicrobial resistance declared a global health crisis, the world urgently needs new classes of antimicrobials. Bacteriocins offer a promising but underexploited avenue — they're naturally produced, can be engineered for specificity, and could potentially spare the microbiome. This review from a top-tier journal maps out exactly where the field stands and why these peptides haven't yet reached the clinic.","specificNumbers":"Nearly 100 years of bacteriocin research · 0 bacteriocins currently approved for human therapeutic use · Narrow and broad spectrum activity documented · Published in Nature Reviews Microbiology (IF ~69)","methodology":"Narrative review published in Nature Reviews Microbiology. The authors surveyed the literature on bacteriocin diversity, structure, mechanisms of action, resistance mechanisms, discovery methods (including metagenomic mining), bioengineering strategies, and barriers to clinical translation.","limitations":"As a narrative review, this paper synthesizes existing knowledge rather than presenting new experimental data. The authors note that most bacteriocins remain incompletely characterized, and the review cannot fully address why clinical translation has been so slow beyond identifying general barriers."},{"rthcId":"RPEP-09341","title":"Safety and efficacy of peptide receptor radionuclide therapy in neuroendocrine tumors: A single center experience.","authors":"Sukrithan, Vineeth; Armbruster, Heather; Rogers, Sherise; Vogt, Sherry Mori; Grenade, Cassandra; Verschraegen, Claire; Zhou, Ye; Goyal, Ashima; Natwa, Mona; Hussein, Akram; Barr, Hallie; Konate, Dramane; Batdorf, Rochelle; Brown, Andrew; Williams, Bonnie; Zhao, Songzhu; Wei, Lai; Xu, Menglin; Shah, Manisha H; Konda, Bhavana","year":2024,"journal":"PloS one, 19(5), e0298824","doi":"10.1371/journal.pone.0298824","pmid":"38748739","tags":["somatostatin-analogs","cancer-therapy","radionuclide-therapy","clinical-trials"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"74% completed all 4 PRRT cycles; 18% objective response rate. Small bowel NETs: median TTF 37.3 months vs pancreatic NETs 13.2 months (p=0.001). Independent predictors of TTF: Ki-67, primary site, liver tumor burden ≥50%. ~40% had grade ≥3 AEs. 10% discontinued for treatment-related AEs. 2 delayed nephrotic syndrome cases. 6 patients had rapid liver failure progression.","whyItMatters":"PRRT is increasingly used for advanced NETs, but clinical trial data (NETTER-1) included mostly small bowel NETs. This real-world study provides critical safety and efficacy data across NET subtypes, identifies patients at highest risk for serious complications, and reports previously unrecognized toxicities like delayed nephrotic syndrome.","specificNumbers":"104 patients. 177Lu-DOTATATE 200 mCi administered every 8 weeks for 4 doses. December 2017 to October 2020.","methodology":"Retrospective single-center analysis of 104 NET patients treated with 177Lu-DOTATATE (200 mCi every 8 weeks for 4 doses) at a US academic center from December 2017 to October 2020. Outcomes: objective response rate, time-to-treatment failure/death, adverse events. Multivariate analysis for predictive factors.","limitations":"Retrospective single-center study with inherent selection bias. No control group. Heterogeneous NET types and prior treatments. Small numbers for subgroup analyses of rare toxicities (2 nephrotic syndrome, 6 liver failure). Median follow-up not clearly stated."},{"rthcId":"RPEP-09342","title":"Effectiveness of Switching CGRP Monoclonal Antibodies in Non-Responder Patients in the UAE: A Retrospective Study.","authors":"Suliman, Reem; Santos, Vanessa; Al Qaisi, Ibrahim; Aldaher, Batool; Al Fardan, Ahmed; Al Barrawy, Hajir; Bader, Yazan; Supena, Jonna Lyn; Alejandro, Kathrina; Alsaadi, Taoufik","year":2024,"journal":"Neurology international, 16(1), 274-288","doi":"10.3390/neurolint16010019","pmid":"38392960","tags":["cgrp","clinical-trials","pain"],"studyType":"cohort","evidenceStrength":"preliminary","keyFinding":"53 migraine patients switched between CGRP mAb classes (CGRP/R to CGRP/L or CGRP/L to CGRP/R). Both switch cohorts showed some clinical improvements. Safety was maintained — adverse events from the first antibody did not recur or worsen after switching classes. Fremanezumab was not included due to UAE unavailability.","whyItMatters":"Up to 30-50% of migraine patients don't respond adequately to their first CGRP antibody. Clinicians face uncertainty about whether switching to a different CGRP antibody — particularly one from a different class — can help. This study provides early real-world evidence that class switching is both safe and potentially effective.","specificNumbers":"53 patients switched between CGRP antibody classes. Studied in a UAE clinical setting.","methodology":"Retrospective real-world study of 53 migraine patients at a UAE center who switched between CGRP mAb classes (eptinezumab, erenumab, galcanezumab) due to lack of efficacy or poor tolerability. Efficacy assessed by clinical improvement measures. Safety evaluated by adverse event monitoring.","limitations":"Small sample size (53 patients) limits statistical power. Retrospective design without a control group. No standardized outcome measures described. Single-center UAE study — population may not be representative. Fremanezumab excluded. Preliminary designation by the authors themselves."},{"rthcId":"RPEP-09343","title":"GLP-1 receptor agonists alleviate colonic inflammation by modulating intestinal microbiota and the function of group 3 innate lymphoid cells.","authors":"Sun, Hanxiao; Shu, Jie; Tang, Jupei; Li, Yue; Qiu, Jinxin; Ding, Zhaoyun; Xuan, Binbin; Chen, Minghui; Gan, Chenxin; Lin, Jinpiao; Qiu, Ju; Sheng, Huiming; Wang, Chuanxin","year":2024,"journal":"Immunology, 172(3), 451-468","doi":"10.1111/imm.13784","pmid":"38544428","tags":["glp-1-receptor-agonists","gut-health","immune-system","inflammation"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"GLP-1RAs ameliorated DSS-induced colitis in both wild-type and T/B-cell-deficient mice via ILC3-dependent IL-22 production. Effect abolished in ILC3-deficient mice. GLP-1RAs increased Firmicutes/Proteobacteria (especially L. reuteri) and decreased pathogenic Staphylococcus. The metabolite DMS was enriched and independently ameliorated colitis while promoting IL-22+ILC3s.","whyItMatters":"This study provides a mechanistic explanation for the anti-inflammatory effects of GLP-1 drugs beyond diabetes. It reveals a gut microbiome-metabolite-immune cell axis that could explain why diabetic patients on GLP-1 RAs may have fewer inflammatory bowel complications and suggests a new therapeutic application for these widely used peptide drugs.","specificNumbers":"GLP-1RAs worked in both wild-type and T/B-cell-deficient mice, proving the mechanism is through innate immunity (ILC3s), not adaptive immunity.","methodology":"Animal study using DSS-induced colitis in wild-type, T/B-cell-deficient, and ILC3-deficient (RORγtgfp/gfp) C57BL/6 mice. GLP-1RA treatment followed by microbiome analysis (16S rRNA), untargeted metabolomics (GC/LC-MS), and immune cell profiling. DMS was independently tested for anti-colitis effects.","limitations":"Mouse colitis model (DSS-induced) doesn't fully replicate human IBD. The microbiota-DMS-ILC3 axis is correlative — direct causation between each step needs further validation. Specific GLP-1 RA used and dosing may not directly translate to human clinical scenarios. No human clinical data."},{"rthcId":"RPEP-09344","title":"Exendin-4 increases the firing activity of hippocampal CA1 neurons through TRPC4/5 channels.","authors":"Sun, Hui-Zhe; Shen, Fang-Shuai; Li, Xiao-Xue; Liu, Cui; Xue, Yan; Han, Xiao-Hua; Chen, Xin-Yi; Chen, Lei","year":2024,"journal":"Neuroscience research, 199, 48-56","doi":"10.1016/j.neures.2023.08.001","pmid":"37595875","tags":["glp-1-receptor-agonists","brain-and-cognition","neuroprotection"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Exendin-4 significantly increased spontaneous firing rate of hippocampal CA1 neurons. The GLP-1 receptor antagonist exendin(9-39) decreased baseline firing, indicating endogenous GLP-1 modulation. The excitatory effect was mediated through TRPC4/TRPC5 ion channels — the first demonstration of this mechanism for GLP-1 in the hippocampus.","whyItMatters":"Understanding how GLP-1 peptides affect brain circuits is crucial as millions take GLP-1 drugs. This study provides the first direct electrophysiological evidence that GLP-1 activates memory-related neurons and identifies the specific ion channel involved. This could explain cognitive benefits reported with GLP-1 drugs and inform Alzheimer's disease research.","specificNumbers":"GLP-1 receptors are widely distributed in the central nervous system. TRPC4/5 channels identified as the molecular mediators.","methodology":"In vivo electrophysiology: multibarrel single-unit extracellular recordings in rat hippocampal CA1 neurons. Micro-pressure administration of exendin-4, exendin(9-39), and TRPC4/5 channel modulators. Firing rate changes quantified as primary outcome.","limitations":"Animal study (rats) with electrophysiology recordings — findings may not directly translate to human brain function. Acute drug application doesn't reflect chronic GLP-1 RA treatment effects. No behavioral or cognitive outcomes measured. Single brain region (CA1) studied."},{"rthcId":"RPEP-09345","title":"Pharmacodynamic and pharmacokinetic profiles of a novel GLP-1 receptor biased agonist-SAL0112.","authors":"Sun, Jingchao; Xiao, Ying; Xing, Wei; Jiang, Wenjuan; Hu, Xuefeng; Li, Hongchao; Liu, Zhaojun; Jin, Qian; Ren, Peng; Zhang, Hongmei; Lobie, Peter E","year":2024,"journal":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 177, 116965","doi":"10.1016/j.biopha.2024.116965","pmid":"38925019","tags":["glp-1-receptor-agonists","drug-delivery","type-2-diabetes"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"SAL0112 demonstrated potent selective Gαs pathway GLP-1R activation without desensitization. Superior stability vs danuglipron in human/rat liver microsomes. Higher oral absorption in rats. Lower DDI potential on liver transporters vs danuglipron. Significant reductions in body weight, blood glucose (p<0.05), HbA1c (p<0.05), and insulin resistance (p<0.01) in diabetic mice. Resolved hepatic steatosis. Efficacy comparable to danuglipron and liraglutide.","whyItMatters":"Most GLP-1 drugs are injectable peptides. The race to develop effective oral GLP-1 drugs is intense, with oral semaglutide being the only approved option. SAL0112 represents a new approach — biased agonism — that could offer better tolerability and fewer side effects while maintaining efficacy as an oral medication.","specificNumbers":"Tested across multiple assay platforms. Liver transporter interactions assessed. Stability tested across multiple species.","methodology":"In vitro: HTRF, FLIPR, TR-FRET, and PathHunter assays for receptor pharmacology. Liver transporter tests in HEK293-OATP1B1/1B3 cells. Stability in multi-species liver microsomes. In vivo: PK in rats; efficacy in high-fat diet transgenic C57BL/6 mice expressing human GLP-1R.","limitations":"Preclinical data only — no human studies. Transgenic mice expressing human GLP-1R don't fully predict human pharmacology. Direct comparison with oral semaglutide (the current market leader) was not performed. Long-term safety and tolerability unknown."},{"rthcId":"RPEP-09346","title":"Identification and utility exploration of a highly potent and long-acting bullfrog GLP-1 analogue in GLP-1 and amylin combination therapy.","authors":"Sun, Xiao; Yang, Dawei; Li, Yan; Shi, Jingjing; Zhang, Xiaolong; Yi, Tingzhuang","year":2024,"journal":"Peptides, 177, 171203","doi":"10.1016/j.peptides.2024.171203","pmid":"38582303","tags":["glp-1-receptor-agonists","amylin","weight-management","natural-peptides"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"bGLP-10 showed superior albumin affinity and receptor potency. At 10 nmol/kg, bGLP-10 significantly outperformed semaglutide in blood sugar reduction and food intake suppression (p<0.001). Chronic combination results: bGLP-10 + cagrilintide = -38.4% weight loss (p<0.001) vs semaglutide + cagrilintide = -23.0% vs bGLP-10 alone = -16.1% vs semaglutide alone = -10.9% vs cagrilintide alone = -5.7%. Superior glucose control and liver lipid management vs semaglutide-cagrilintide (p<0.001).","whyItMatters":"The combination of GLP-1 and amylin analogues is the next frontier in obesity treatment (Novo Nordisk's CagriSema is in phase 3 trials). This study suggests that natural GLP-1 peptides from non-mammalian species may be even more effective than current drugs, and that the right GLP-1-amylin combination could achieve unprecedented weight loss levels.","specificNumbers":"10 bGLP-1 analogues designed. bGLP-10 showed superior albumin affinity and receptor potency. Outperformed semaglutide in DIO mice.","methodology":"In vitro receptor binding and activation assays. In vivo: diet-induced obesity (DIO) mice on high-fat diet. Acute studies for blood sugar and food intake. Chronic combination study with bGLP-10 and/or cagrilintide vs semaglutide and/or cagrilintide. Outcomes: body weight, blood glucose, liver lipids.","limitations":"Mouse study only — DIO mice don't fully model human obesity. No pharmacokinetic data in larger animals or humans. No safety/tolerability assessment. The comparison to semaglutide may not reflect optimized dosing. bGLP-10 is a novel compound with no clinical development track record."},{"rthcId":"RPEP-09347","title":"Liraglutide alleviates ferroptosis in renal ischemia reperfusion injury via inhibiting macrophage extracellular trap formation.","authors":"Sun, Zejia; Zhang, Feilong; Gao, Zihao; Wu, Jiyue; Bi, Qing; Zheng, Xiang; Zhang, Jiandong; Cao, Peng; Wang, Wei","year":2024,"journal":"International immunopharmacology, 142(Pt B), 113258","doi":"10.1016/j.intimp.2024.113258","pmid":"39340991","tags":["glp-1-receptor-agonists","kidney-health","organ-protection"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Liraglutide relieved renal ischemia-reperfusion injury and ferroptosis in vivo. It inhibited macrophage extracellular trap (MET) formation both in vivo and in vitro. Liraglutide decreased STAT1 phosphorylation and increased STAT3/6 phosphorylation, promoting M2 macrophage polarization. STAT3/6 inhibition reversed all liraglutide protective effects.","whyItMatters":"Kidney transplantation and major surgery frequently cause ischemia-reperfusion injury, and there are no approved drugs to prevent it. This study identifies a specific, druggable mechanism by which a widely available GLP-1 drug protects the kidneys — through macrophage polarization and ferroptosis prevention — opening a potential new indication for liraglutide.","specificNumbers":"72 mice used, 8 per group. Both in vivo kidney injury model and in vitro co-culture system employed.","methodology":"Animal study: 72 C57BL/6J mice (8 per group) with surgically induced renal ischemia-reperfusion injury. In vitro co-culture of primary tubular epithelium with RAW264.7 macrophages under hypoxia/reoxygenation. METs measured by extracellular DNA, neutrophil elastase, and myeloperoxidase. F4/80 and citH3 immunofluorescence for MET visualization.","limitations":"Mouse model — surgical ischemia in mice doesn't fully replicate human kidney transplantation or acute kidney injury. Liraglutide dosing and timing in the mouse model may not translate directly to clinical use. No long-term kidney function or histology follow-up. RAW264.7 is an immortalized cell line that may not fully represent primary macrophages."},{"rthcId":"RPEP-09348","title":"Efficacy and Safety of Adding Empagliflozin to Liraglutide on Renal Function in Patients with Advanced-Stage Type 2 Diabetic Kidney Disease: A Randomized Controlled Trial.","authors":"Sunagawa, Kae; Hirai, Keiji; Sunagawa, Sumito; Kamiya, Norifumi; Komesu, Isao; Sunagawa, Yusako; Sunagawa, Hiroshi; Nakachi, Ken; Hirai, Aizan; Ookawara, Susumu; Morishita, Yoshiyuki","year":2024,"journal":"Diabetes, metabolic syndrome and obesity : targets and therapy, 17, 3767-3781","doi":"10.2147/DMSO.S471535","pmid":"39430135","tags":["glp-1-receptor-agonists","kidney-health","type-2-diabetes","clinical-trials"],"studyType":"RCT","evidenceStrength":"moderate","keyFinding":"Adding empagliflozin to liraglutide did not improve eGFR (primary outcome), urinary protein excretion, or glycemic control over 6 months. Empagliflozin significantly increased hemoglobin (12.9→13.7 g/dL, p<0.05) and decreased body weight (66.1→64.5 kg, p<0.05). No significant differences in blood pressure, lipids, or HbA1c.","whyItMatters":"Both GLP-1 RAs and SGLT2 inhibitors have shown kidney benefits individually. Clinicians increasingly combine these drugs, but evidence for their combined benefit in advanced kidney disease is lacking. This negative result suggests that in advanced-stage disease, the combination may not offer additive kidney protection over GLP-1 RA alone.","specificNumbers":"41 patients randomized 1:1. Liraglutide at 1.8 mg/day. Treatment period: 12 months total.","methodology":"Open-label RCT, 41 patients randomized 1:1. Liraglutide 0.3-0.9 mg/day subcutaneous. Empagliflozin 10 mg daily oral added at 6 months in treatment group. Primary outcome: eGFR change during months 6-12. Secondary outcomes: body weight, blood pressure, hemoglobin, lipids, glucose, HbA1c, urine protein/creatinine ratio.","limitations":"Very small sample (41 patients). Open-label design introduces bias. Short 6-month combination period may be insufficient to detect kidney benefit. Japanese population with liraglutide dosing (max 0.9 mg) lower than Western standards (1.8 mg). Advanced kidney disease may have limited reversibility."},{"rthcId":"RPEP-09349","title":"Discovery of a novel nanomolar angiotensin-I converting enzyme inhibitory peptide with unusual binding mechanisms derived from Chlorella pyrenoidosa.","authors":"Suo, Qishan; Wang, Jing; Wu, Ning; Geng, Lihua; Zhang, Quanbin; Yue, Yang","year":2024,"journal":"International journal of biological macromolecules, 280(Pt 2), 135873","doi":"10.1016/j.ijbiomac.2024.135873","pmid":"39307496","tags":["bioactive-peptides","cardiovascular-health","antioxidant-effects"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"99 peptides identified from Chlorella by LC-MS/MS. LVAKA (LV-5) IC50: 26.66 μM for ACE inhibition. Three peptides (LV-5, LKKAP, PGLRP) stable at extreme pH and temperature. Sequence optimization yielded LRAKA (LR-5): nanomolar ACE inhibition (IC50: 350 nM in vitro) and in vivo blood pressure reduction in rats. LR-5 binds an unconventional ACE site.","whyItMatters":"Most food-derived ACE-inhibitory peptides have micromolar potency, limiting practical utility. LR-5's nanomolar potency is exceptional — approaching pharmaceutical-grade activity. Combined with digestive stability and in vivo blood pressure reduction, this represents one of the most promising food-derived antihypertensive peptides discovered.","specificNumbers":"99 peptides identified by LC-MS/MS. 10 selected by virtual screening. Lead peptide showed nanomolar ACE inhibition.","methodology":"Trypsin hydrolysis of Chlorella pyrenoidosa. LC-MS/MS peptide identification (99 peptides). Virtual screening by molecular docking. In vitro ACE inhibition assays. Stability testing under pH/temperature extremes and simulated gastrointestinal digestion. Sequence optimization. In vivo blood pressure testing in rats. Molecular dynamics simulation for binding mechanism.","limitations":"Animal study (rats) for in vivo validation — human blood pressure data needed. The optimization from LV-5 to LR-5 creates a semi-synthetic peptide, not purely 'natural.' Oral bioavailability in humans not confirmed. Single animal study may not reflect clinical efficacy."},{"rthcId":"RPEP-09350","title":"Can calcitonin gene-related peptide monoclonal antibodies ameliorate writer's cramp and migraine?","authors":"Suzuki, Keisuke; Suzuki, Shiho; Fujita, Hiroaki; Sakuramoto, Hirotaka; Shioda, Mukuto; Hirata, Koichi","year":2024,"journal":"Neuropsychopharmacology reports, 44(2), 482-484","doi":"10.1002/npr2.12444","pmid":"38602109","tags":["cgrp","brain-and-cognition","pain"],"studyType":"case series","evidenceStrength":"preliminary","keyFinding":"Erenumab treatment for 3 months improved symptoms of both focal task-specific dystonia (writer's cramp) and migraine in a single patient. This is the first case report of CGRP mAb improving dystonia, suggesting a potential role for CGRP in dystonia pathophysiology.","whyItMatters":"Writer's cramp and other focal dystonias are difficult to treat — botulinum toxin injections are the main option but have limitations. If CGRP is involved in dystonia pathophysiology, CGRP antibodies could represent an entirely new treatment approach for these debilitating movement disorders.","specificNumbers":"First reported case of anti-CGRP mAb improving dystonia. Patient had both migraine and writer's cramp.","methodology":"Single case report. Patient with comorbid migraine and writer's cramp treated with erenumab (CGRP receptor antibody) due to increasing monthly migraine days. Both conditions assessed clinically before and after 3 months of treatment.","limitations":"Single case report — the lowest level of evidence. Could be coincidental improvement, placebo effect, or natural disease fluctuation. No objective dystonia measures described. Cannot establish causation from a single observation."},{"rthcId":"RPEP-09351","title":"Real-world effectiveness of erenumab in Japanese patients with migraine.","authors":"Suzuki, Keisuke; Suzuki, Shiho; Shiina, Tomohiko; Haruyama, Yasuo; Kobayashi, Saro; Shioda, Mukuto; Hirata, Koichi","year":2024,"journal":"Heliyon, 10(4), e26568","doi":"10.1016/j.heliyon.2024.e26568","pmid":"38420497","tags":["cgrp","clinical-trials","pain"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Cumulative 85% response rate (≥30% MMD reduction) over 6 months. Response rates: 36% at 1 month, 47% at 3 months, 63% at 6 months. CGRP mAb-naïve: 56% early responders. CGRP mAb-switching: 26% early responders, 59% late responders. Wearing-off (increased migraines week 2→4): 2.4-12.5%. Only 11.1% had adverse events (all mild).","whyItMatters":"This study demonstrates that erenumab works in highly treatment-resistant patients and those switching from other CGRP antibodies — two populations with limited real-world data, especially in Asian populations. The finding that switchers need 4-6 months to respond has direct clinical implications for treatment evaluation timelines.","specificNumbers":"45 patients. 60% switching from other CGRP mAbs. 66.7% had ≥4 prior prophylaxis failures. 6-month follow-up.","methodology":"Single-center 6-month prospective cohort of 45 Japanese migraine patients treated with erenumab. Monthly migraine days tracked. Early (1-3 months) and late (4-6 months) responder patterns analyzed. Wearing-off assessed by comparing weekly migraine days between weeks 2 and 4 of each month.","limitations":"Small sample (45 patients), single-center, non-controlled. Asian-specific findings may not generalize. The 30% response threshold is a relatively low bar. No standardized reason for switching documented. Japanese erenumab dosing may differ from Western practice."},{"rthcId":"RPEP-09352","title":"Tirzepatide ameliorates eating behaviors regardless of prior exposure to glucagon-like peptide receptor agonists in Japanese patients with type 2 diabetes mellitus.","authors":"Suzuki, Toru; Sato, Tatsuya; Tanaka, Marenao; Endo, Keisuke; Nakata, Kei; Ogawa, Toshifumi; Hosaka, Itaru; Akiyama, Yukinori; Umetsu, Araya; Furuhashi, Masato","year":2024,"journal":"Journal of diabetes and its complications, 38(7), 108779","doi":"10.1016/j.jdiacomp.2024.108779","pmid":"38833854","tags":["glp-1-receptor-agonists","appetite-and-metabolism","type-2-diabetes"],"studyType":"cohort","evidenceStrength":"preliminary","keyFinding":"Over 6 months: HbA1c 7.3%→6.0%→5.8%. Body weight 87.7→82.0→79.6 kg. Eating behavior score 57.0→50.7→45.9. GLP-1RA-naïve (n=20): eating behavior changes mainly in first 3 months. GLP-1RA non-naïve (n=13): eating behavior changes continued through 6 months. No correlation between eating behavior changes and weight/glucose changes.","whyItMatters":"Weight loss drugs are often criticized as purely metabolic interventions that don't address the behavioral and psychological aspects of overeating. This study suggests tirzepatide may actually change how people relate to food — an effect that appears independent of its metabolic benefits and could contribute to more sustainable weight management.","specificNumbers":"33 patients, mean age 51.8 years. Tirzepatide started at 2.5 mg/week for 4 weeks, then 5.0 mg/week, for 6 months total.","methodology":"Prospective cohort of 33 Japanese T2DM patients (mean age 51.8 years). Tirzepatide 2.5 mg/week for 4 weeks, then 5.0 mg/week. Validated eating behavior questionnaire at baseline, 3 months, and 6 months. Subgroup analysis by prior GLP-1 RA exposure.","limitations":"Small sample (33 patients). No control group. Japanese population with lower BMI and tirzepatide doses than Western studies. Validated questionnaire is subjective. 6 months may not capture long-term behavioral sustainability. Eating behavior assessment doesn't distinguish between hunger reduction and true behavioral change."},{"rthcId":"RPEP-09353","title":"Semaglutide treatment of hypothalamic obesity - a real-life data study.","authors":"Svendstrup, Mathilde; Rasmussen, Aase Krogh; Kistorp, Caroline; Klose, Marianne; Andreassen, Mikkel","year":2024,"journal":"Pituitary, 27(5), 685-692","doi":"10.1007/s11102-024-01429-5","pmid":"39120810","tags":["glp-1-receptor-agonists","semaglutide","weight-management","brain-and-cognition"],"studyType":"cohort","evidenceStrength":"preliminary","keyFinding":"26 patients with hypothalamic obesity treated with semaglutide (median dose 1.6 mg). Mean weight loss: 13.4 kg (95% CI: 10.3-16.5 kg, p<0.001). Mean BMI reduction: 4.4 kg/m² (95% CI: 3.4-5.4, p<0.001). 25/26 patients (96%) lost weight. 15 patients (58%) lost >10% body weight. 2 patients (8%) lost >20%.","whyItMatters":"Hypothalamic obesity is one of the most devastating complications of brain tumors and their treatment. Until now, no pharmacotherapy has shown meaningful benefit. This study provides the first real evidence that GLP-1 drugs can work even when the brain's normal appetite circuits are destroyed — suggesting they act through alternative neural pathways.","specificNumbers":"Patients tracked at the Department of Endocrinology, Rigshospitalet. Weight data collected before and after semaglutide initiation.","methodology":"Real-world retrospective cohort study at Rigshospitalet, Copenhagen (September 2020 to November 2023). 26 patients with acquired hypothalamic obesity (15 females, median age 52, range 18-65). Semaglutide at median dose 1.6 mg (range 0.5-2.5 mg). Weight tracked before and during treatment.","limitations":"Small cohort (26 patients). Retrospective design without control group. Variable follow-up duration. No information on diet/exercise changes during treatment. The heterogeneous nature of hypothalamic injury (different tumors, different surgical approaches) limits generalizability. Long-term weight stability after treatment not assessed."},{"rthcId":"RPEP-09354","title":"Intranasal oxytocin in a genetic animal model of autism.","authors":"Szabó, Jakub; Mlynár, Matúš; Feješ, Andrej; Renczés, Emese; Borbélyová, Veronika; Ostatníková, Daniela; Celec, Peter","year":2024,"journal":"Molecular psychiatry, 29(2), 342-347","doi":"10.1038/s41380-023-02330-6","pmid":"38102481","tags":["oxytocin","brain-and-cognition","mental-health"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Daily intranasal oxytocin (0.8 IU/kg for 4 weeks): 2x more social interaction time from week 2. 50% reduced explorative behavior at 4 weeks. 30% reduction in repetitive behavior persisting 4 weeks post-treatment. Effects lasted 4 weeks after treatment ended. However, ~10% increase in social disinterest also observed.","whyItMatters":"ASD core symptoms (social deficits, repetitive behaviors) have no approved pharmacological treatment. Oxytocin has long been a candidate, but clinical trial results have been ambiguous. This study in a genetic model shows clear, lasting benefits — but also reveals concerning social ambivalence that may explain mixed clinical results and demands careful investigation.","specificNumbers":"Oxytocin is a neuropeptide. Delivered intranasally in a genetic ASD mouse model.","methodology":"Animal study using Shank3-/- adult mice (genetic autism model). Daily intranasal oxytocin (0.8 IU/kg) for 4 weeks. Behavioral testing during treatment (weeks 2, 4) and post-treatment (4 weeks after cessation). Outcomes: social interaction time, explorative behavior, repetitive behaviors, social disinterest. Published in Molecular Psychiatry.","limitations":"Mouse model — Shank3 knockout represents only a subset of ASD. Behavioral tests may not fully capture human social complexity. The 10% increase in social disinterest is concerning and poorly understood. No dose-response or long-term safety data. Intranasal delivery in mice differs from human nasal anatomy."},{"rthcId":"RPEP-09355","title":"New Developments in Pharmacological Treatment of Obesity and Type 2 Diabetes-Beyond and within GLP-1 Receptor Agonists.","authors":"Sztanek, Ferenc; Tóth, László Imre; Pető, Attila; Hernyák, Marcell; Diószegi, Ágnes; Harangi, Mariann","year":2024,"journal":"Biomedicines, 12(6)","doi":"10.3390/biomedicines12061320","pmid":"38927527","tags":["glp-1-receptor-agonists","amylin","weight-management","type-2-diabetes"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"GLP-1 RAs may face efficacy plateaus due to receptor desensitization. Tirzepatide's dual GLP-1/GIP agonism offers superior weight loss and glycemic control. Triple agonists (GLP-1/GIP/glucagon) represent the next frontier. Oral GLP-1 formulations are expanding access. Understanding intercellular signaling and inflammatory pathways is key to developing next-generation agents.","whyItMatters":"The GLP-1 drug revolution is just beginning. This review contextualizes where we are — from established single agonists to the frontier of triple agonists — and addresses the critical question of whether receptor desensitization limits long-term efficacy, a concern for patients on lifelong therapy.","specificNumbers":"Review covers GLP-1 RAs, dual GIP/GLP-1 agonists (tirzepatide), triple agonists (GLP-1/GIP/glucagon), and amylin-based therapies.","methodology":"Narrative review covering published clinical trials, mechanistic studies, and emerging drug pipeline data on incretin-based peptide therapies for obesity and type 2 diabetes.","limitations":"Narrative review with inherent selection bias in study inclusion. Doesn't provide quantitative meta-analytic synthesis. Triple agonist data is mostly preclinical or early-phase. Long-term desensitization concerns are theoretical rather than conclusively demonstrated in large trials."},{"rthcId":"RPEP-09356","title":"Superior metabolic improvement of polycystic ovary syndrome traits after GLP1-based multi-agonist therapy.","authors":"Sánchez-Garrido, Miguel A; Serrano-López, Víctor; Ruiz-Pino, Francisco; Vázquez, María Jesús; Rodríguez-Martín, Andrea; Torres, Encarnación; Velasco, Inmaculada; Rodríguez, Ana Belén; Chicano-Gálvez, Eduardo; Mora-Ortiz, Marina; Ohlsson, Claes; Poutanen, Matti; Pinilla, Leonor; Gaytán, Francisco; Douros, Jonathan D; Yang, Bin; Müller, Timo D; DiMarchi, Richard D; Tschöp, Matthias H; Finan, Brian; Tena-Sempere, Manuel","year":2024,"journal":"Nature communications, 15(1), 8498","doi":"10.1038/s41467-024-52898-y","pmid":"39353946","tags":["glp-1-receptor-agonists","hormonal-peptides","weight-loss","diabetes"],"studyType":"RCT","evidenceStrength":"strong","keyFinding":"GLP-1/Estrogen showed superior efficacy versus GLP-1/GIP, GLP-1/GIP/Glucagon, and metformin for metabolic complications of PCOS in mice. GLP-1/E also improved ovarian cyclicity in an ovulatory PCOS model without direct estrogenic effects on the uterus (no uterotrophic effects). Proteomics revealed GLP-1/E changes hypothalamic pathways differently between the two PCOS models, explaining variable effectiveness.","whyItMatters":"PCOS affects up to 13% of women of reproductive age and current treatments are mostly symptomatic. GLP-1-based multi-agonists could address both the metabolic (obesity, insulin resistance) and reproductive (anovulation) aspects of PCOS simultaneously, especially if estrogen can be delivered to the brain without systemic estrogenic effects.","specificNumbers":"Not specified in abstract — results in full text.","methodology":"Animal study using two mouse models of PCOS with variable metabolic and reproductive traits. Mice received GLP-1/E, GLP-1/GIP, GLP-1/GIP/Glucagon, or metformin. Hormonal, metabolic, and gonadal responses were measured. Quantitative proteomics analyzed hypothalamic pathway changes.","limitations":"Mouse study only — PCOS mouse models have significant limitations in representing human disease. No human dosing or safety data. The GLP-1/E conjugate is experimental and not commercially available. Proteomics reveals associations, not causation. Short-term treatment only."},{"rthcId":"RPEP-09357","title":"Comparing Glucagon-like peptide-1 receptor agonists versus metformin in drug-naive patients: A nationwide cohort study.","authors":"Sørensen, Kathrine Kold; Gerds, Thomas Alexander; Køber, Lars; Loldrup Fosbøl, Emil; Poulsen, Henrik Enghusen; Møller, Amalie Lykkemark; Andersen, Mikkel Porsborg; Pedersen-Bjergaard, Ulrik; Torp-Pedersen, Christian; Zareini, Bochra","year":2024,"journal":"Journal of diabetes, 16(10), e70000","doi":"10.1111/1753-0407.70000","pmid":"39364788","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09358","title":"The Foundational Science of Endogenous Opioids and Their Receptors.","authors":"Tache, Simona; Kerr, Patrick L; Sirbu, Cristian","year":2024,"journal":"Advances in neurobiology, 35, 9-26","doi":"10.1007/978-3-031-45493-6_2","pmid":"38874716","tags":["neuropeptides","pain","brain-and-cognition"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Four endogenous opioid peptide families (beta-endorphin, enkephalin, dynorphin, endomorphin) act through multiple receptor types (mu, delta, kappa, ORL1). The EOS mediates pain modulation, reward behaviors, stress response, immune function, and social bonding. These systems have extensive cross-talk with other neurotransmitter and hormonal systems.","whyItMatters":"Understanding the endogenous opioid system is essential for grasping how the body manages pain, pleasure, and stress. This is particularly relevant given the opioid crisis — knowing how natural opioid peptides work helps explain addiction vulnerability and informs the development of safer pain treatments.","specificNumbers":"Four major peptide families: beta-endorphin, enkephalin, dynorphin, and endomorphin, acting through multiple receptor types.","methodology":"Narrative book chapter review (Advances in Neurobiology, volume 35). Synthesizes established literature on opioid peptide biochemistry, receptor pharmacology, and systems neuroscience.","limitations":"Book chapter format — necessarily simplified and not a systematic review. Rapidly evolving field means some recent discoveries may not be covered. The chapter focuses on structure and basic function rather than clinical applications."},{"rthcId":"RPEP-09359","title":"Glucagon-like peptide receptor agonists and risk for depression.","authors":"Tagliapietra, Gabriella A; Cantrell, Matthew A; Lund, Brian C","year":2024,"journal":"Primary care diabetes, 18(4), 422-426","doi":"10.1016/j.pcd.2024.05.005","pmid":"38852027","tags":["glp-1-receptor-agonists","mental-health","safety-and-side-effects"],"studyType":"cohort","evidenceStrength":"strong","keyFinding":"Incident depression within 1 year: GLP-1 RA group 7.7% (2,263/34,130) vs DPP-4i group 6.3% (6,602/105,478). Adjusted relative risk: 1.02 (95% CI: 0.97-1.07, not significant). All sensitivity analyses also non-significant.","whyItMatters":"FDA labeling warnings about suicidal thoughts and behaviors on GLP-1 weight-loss drugs have caused significant patient and clinician concern. This large real-world study provides reassuring evidence that GLP-1 drugs don't increase depression risk — critical safety data as millions of people start these medications.","specificNumbers":"Study period: June 2013 to June 2020. Compared GLP-1RA vs. DPP-4 inhibitor initiators in the Veterans Health Administration.","methodology":"Retrospective cohort study using VA healthcare data (June 2013-June 2020). 34,130 GLP-1 RA initiators vs 105,478 DPP-4i initiators. Primary outcome: incident depression (new diagnosis or new antidepressant) within 1 year. Multivariable log-binomial regression adjusting for demographics, comorbidities, prior medications.","limitations":"Retrospective observational design — cannot prove causation. VA population is predominantly male and older, limiting generalizability. Depression detection relies on diagnosis codes and antidepressant prescriptions, which may miss cases. Only 1-year follow-up. Did not separate individual GLP-1 RAs or doses. DPP-4i comparator may also have mental health effects."},{"rthcId":"RPEP-09360","title":"CGRP-monoclonal antibodies in Japan: insights from an online survey of physician members of the Japanese headache society.","authors":"Takizawa, Tsubasa; Ihara, Keiko; Watanabe, Narumi; Takemura, Ryo; Takahashi, Nobuyuki; Miyazaki, Naoki; Shibata, Mamoru; Suzuki, Keisuke; Imai, Noboru; Suzuki, Norihiro; Hirata, Koichi; Takeshima, Takao; Nakahara, Jin","year":2024,"journal":"The journal of headache and pain, 25(1), 39","doi":"10.1186/s10194-024-01737-y","pmid":"38491415","tags":["cgrp","clinical-trials"],"studyType":"cohort","evidenceStrength":"preliminary","keyFinding":"320/397 respondents (81%) had prescribed CGRP mAbs. 55% required ≥2 prior preventive failures. MMD thresholds varied: ≥4 (23%), ≥6 (22%), ≥8 (24%), ≥10 (26%). 70% assessed efficacy at 3 months for episodic migraine. Cost was the top concern: 28% cited it as limiting prescriptions and 24% as the main reason responding patients discontinued.","whyItMatters":"CGRP antibodies are transforming migraine prevention, but their high cost creates a gap between what's medically optimal and what's practically achievable. This survey quantifies that gap in Japan and reveals significant variability in prescribing thresholds among specialists — information important for guideline development and health policy.","specificNumbers":"Japanese CGRP mAb guidelines: ≥4 monthly migraine days and ≥1 previous preventive failure required.","methodology":"Online survey of Japanese Headache Society physician members. Questions covered prescribing experience, threshold criteria (prior failures, monthly migraine days), efficacy assessment timing, and barriers to treatment. 397 responses analyzed.","limitations":"Survey-based — reflects reported practices, not verified prescribing data. Self-selected respondents may not represent all Japanese prescribers. Japanese healthcare system and CGRP mAb pricing differ from other countries. Physician perspectives may not reflect patient experiences or preferences."},{"rthcId":"RPEP-09361","title":"Bridging the gap between GLP1-receptor agonists and cardiovascular outcomes: evidence for the role of tirzepatide.","authors":"Taktaz, Fatemeh; Fontanella, Rosaria Anna; Scisciola, Lucia; Pesapane, Ada; Basilicata, Manuela Giovanna; Ghosh, Puja; Franzese, Martina; Tortorella, Giovanni; Puocci, Armando; Vietri, Maria Teresa; Capuano, Annalisa; Paolisso, Giuseppe; Barbieri, Michelangela","year":2024,"journal":"Cardiovascular diabetology, 23(1), 242","doi":"10.1186/s12933-024-02319-7","pmid":"38987789","tags":["glp-1-receptor-agonists","cardiovascular-health","type-2-diabetes"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Tirzepatide's dual mechanism may provide cardiovascular protection through: (1) anti-inflammatory effects, (2) anti-apoptotic activity, (3) autophagy promotion, (4) atherosclerosis reduction, (5) indirect benefits via blood pressure, weight, and lipid improvements. GIP receptor activation adds mechanisms beyond GLP-1 alone. Heart failure trials are underway.","whyItMatters":"GLP-1 RA cardiovascular outcome trials (like SELECT and SUSTAIN-6) have changed diabetes care. The question now is whether tirzepatide's added GIP agonism provides even better cardiovascular protection. This review makes the mechanistic case for why it might, informing expectations for ongoing cardiac outcome trials.","specificNumbers":"Tirzepatide targets both GLP-1 and GIP receptors. GLP-1 RAs have proven cardiovascular benefits in major outcome trials.","methodology":"Narrative review published in Cardiovascular Diabetology. Synthesizes preclinical mechanistic data, clinical trial results, and pharmacological evidence on tirzepatide's cardiovascular effects.","limitations":"Narrative review — inherently selective in evidence presentation. Much of the cardiovascular mechanism data is preclinical. Dedicated tirzepatide cardiovascular outcome trials (SURPASS-CVOT) have not yet reported. The distinction between GLP-1 and GIP cardiovascular contributions is not fully established."},{"rthcId":"RPEP-09362","title":"The Dispensing Error Rate in an App-Based, Semaglutide-Supported Weight-Loss Service: A Retrospective Cohort Study.","authors":"Talay, Louis; Vickers, Matt","year":2024,"journal":"Pharmacy (Basel, Switzerland), 12(5)","doi":"10.3390/pharmacy12050135","pmid":"39311126","tags":["glp-1-receptor-agonists","semaglutide","weight-management","safety-and-side-effects"],"studyType":"cohort","evidenceStrength":"preliminary","keyFinding":"Semaglutide dispensing errors occurred in only 0.35% of 28,165 orders, with incorrect dose being the most common error type at 58.6% of all errors.","whyItMatters":"As GLP-1 medications become increasingly prescribed through digital health platforms, this study provides the first evidence that app-based dispensing error rates are relatively low, though dose errors remain a concern requiring vigilance.","specificNumbers":"Australia's largest app-based semaglutide weight loss service. Dispensing error rates analyzed from pharmacy partners.","methodology":"Retrospective cohort study analyzing dispensing error reports from patient-selected and partner pharmacies of Australia's largest digital weight loss service over six months.","limitations":"Single provider in one country; relied on patient-reported errors which may undercount actual mistakes; six-month window may not capture seasonal patterns; no comparison to traditional pharmacy dispensing error rates."},{"rthcId":"RPEP-09363","title":"The Effect of Lifestyle Coaching Design on Patient Engagement and Weight Loss in Non-diabetic Patients of a Semaglutide-Supported Digital Obesity Program in the UK: A Comparative Retrospective Cohort Study.","authors":"Talay, Louis A; Vickers, Matt; Lagesen, Leif; Liu, Nicole","year":2024,"journal":"Cureus, 16(11), e74321","doi":"10.7759/cureus.74321","pmid":"39583610","tags":["glp-1-receptor-agonists","semaglutide","weight-management"],"studyType":"cohort","evidenceStrength":"preliminary","keyFinding":"Proactive coaching doubled patient engagement metrics (19.4 vs 8.6 messages) but weight loss difference (10.1% vs 8.9%) was not statistically significant over 16 weeks.","whyItMatters":"As digital GLP-1 weight loss services proliferate, understanding whether investing in more intensive coaching translates to better outcomes helps optimize program design and resource allocation.","specificNumbers":"154 patients over 16 weeks in a UK digital weight loss service. Comparative analysis of different coaching designs.","methodology":"Retrospective comparative cohort study of 154 non-diabetic patients in a UK digital semaglutide weight loss program, comparing proactive/personalized vs reactive/standardized coaching over 16 weeks.","limitations":"Small sample size (154 patients); short 16-week follow-up; retrospective design without randomization; single digital health provider; no medication-only control group for direct comparison."},{"rthcId":"RPEP-09364","title":"Molecular mechanisms of semaglutide and liraglutide as a therapeutic option for obesity.","authors":"Tamayo-Trujillo, Rafael; Ruiz-Pozo, Viviana A; Cadena-Ullauri, Santiago; Guevara-Ramírez, Patricia; Paz-Cruz, Elius; Zambrano-Villacres, Raynier; Simancas-Racines, Daniel; Zambrano, Ana Karina","year":2024,"journal":"Frontiers in nutrition, 11, 1398059","doi":"10.3389/fnut.2024.1398059","pmid":"38742021","tags":["glp-1-receptor-agonists","semaglutide","weight-management","appetite-and-metabolism"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Semaglutide and liraglutide act through five key molecular pathways: appetite regulation via hypothalamic signaling, enhanced insulin secretion, glucose homeostasis, increased energy expenditure, and improved lipid metabolism.","whyItMatters":"Understanding exactly how GLP-1 drugs work at the molecular level helps researchers develop next-generation obesity treatments and helps clinicians predict which patients will benefit most from these therapies.","specificNumbers":"Obesity is associated with cardiovascular disease, type 2 diabetes, hypertension, and certain cancers. Global prevalence is increasing.","methodology":"Minireview synthesizing published research on the molecular mechanisms of action of semaglutide and liraglutide in obesity-related metabolic pathways.","limitations":"Minireview format without systematic search methodology; focuses primarily on semaglutide and liraglutide without comprehensive comparison to newer GLP-1 agents; does not cover emerging combination therapies like tirzepatide."},{"rthcId":"RPEP-09365","title":"Real-World Effectiveness of Once-Weekly Glucagon-Like Peptide-1 Receptor Agonists (OW GLP-1RAs) in Comparison with Dipeptidyl Peptidase-4 Inhibitors (DPP-4is) for Glycemic Control and Weight Outcomes in Type 2 Diabetes Mellitus (RELATE).","authors":"Tan, Xi; Divino, Victoria; Amamoo, James; Xie, Lin; Coyle, Katharine B; Gamble, Cory L; Guevarra, Mico; Paprocki, Yurek; King, Aaron A","year":2024,"journal":"Clinical drug investigation, 44(4), 271-284","doi":"10.1007/s40261-024-01354-2","pmid":"38507188","tags":["glp-1-receptor-agonists","type-2-diabetes","weight-management"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Semaglutide users achieved 1.7% HbA1c reduction and 4.1 kg weight loss vs 0.9% and 1.3 kg for DPP-4 inhibitor users over 12 months, with GLP-1 patients at least twice as likely to hit composite endpoints.","whyItMatters":"While clinical trials have established GLP-1 superiority, this real-world evidence confirms those benefits hold up in everyday clinical practice, supporting guideline recommendations to prioritize GLP-1 therapies for patients needing both glycemic control and weight management.","specificNumbers":"Compared two treatment cohorts. Primary outcomes: HbA1c and weight changes.","methodology":"Observational cohort study using linked IQVIA PharMetrics Plus and Ambulatory EMR databases (January 2017–April 2022), with inverse probability of treatment weighting to adjust for baseline differences between groups.","limitations":"Observational design limits causal inference despite statistical adjustments; US-focused data may not generalize globally; relatively small semaglutide subgroup (N=354); limited to 12-month follow-up; potential for residual confounding."},{"rthcId":"RPEP-09366","title":"Real-world clinical results of CGRP monoclonal antibody treatment for medication overuse headache of migraine without abrupt drug discontinuation and no hospitalization.","authors":"Tanei, Takafumi; Fuse, Yutaro; Maesawa, Satoshi; Nishimura, Yusuke; Ishizaki, Tomotaka; Nagashima, Yoshitaka; Mutoh, Manabu; Ito, Yoshiki; Hashida, Miki; Suzuki, Takahiro; Yamamoto, Syun; Wakabayashi, Toshihiko; Saito, Ryuta","year":2024,"journal":"Heliyon, 10(22), e40190","doi":"10.1016/j.heliyon.2024.e40190","pmid":"39748981","tags":["cgrp","pain","clinical-trials"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"After three CGRP-mAb injections, monthly headache days decreased from median 30.0 to 9.5, with 75% of patients achieving ≥50% reduction in headache frequency without abrupt medication discontinuation.","whyItMatters":"Medication overuse headache affects millions of migraine patients, and the standard treatment of abrupt drug withdrawal is notoriously difficult to maintain. This approach offers a gentler alternative that may improve compliance and patient quality of life.","specificNumbers":"Data collected at baseline and 1 month after each injection. Multiple outcome measures tracked.","methodology":"Real-world prospective cohort study of 33 migraine patients with medication overuse headache, measuring outcomes at baseline and after each of three monthly CGRP monoclonal antibody injections.","limitations":"Small sample size (33 patients); no control group or comparison with standard abrupt withdrawal; single-center study in Japan; short follow-up of three months; open-label design introduces potential placebo effects."},{"rthcId":"RPEP-09367","title":"Practical Applications of a Nausea and Vomiting Model in the Clinical Development of Additional Doses of Dulaglutide.","authors":"Tang, Cheng Cai; Lim, Jean; Loo, Li Shen; Jung, Heike; Konig, Manige; Tham, Lai San","year":2024,"journal":"Journal of clinical pharmacology, 64(2), 215-226","doi":"10.1002/jcph.2373","pmid":"37853524","tags":["glp-1-receptor-agonists","safety-and-side-effects","type-2-diabetes"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"A minimum 4-week duration at each dulaglutide dose before escalation was validated as appropriate to reduce gastrointestinal events, consistent with AWARD-11 observed data.","whyItMatters":"GI side effects are the most common reason patients discontinue GLP-1 medications. This model-informed approach provides the evidence base for dosing recommendations that help patients tolerate higher, more effective doses.","specificNumbers":"Dulaglutide 3.0 and 4.5 mg weekly approved for additional glycemic control. 4-week intervals between dose increments recommended.","methodology":"Markov chain Monte Carlo pharmacokinetic/pharmacodynamic joint modeling using AWARD-11 trial data (N=1,842) to simulate nausea and vomiting probabilities across various dose escalation scenarios.","limitations":"Model-based predictions may not capture all real-world variability; based on clinical trial population that may not represent all patients; focused only on nausea and vomiting (not other GI effects like diarrhea); dulaglutide-specific findings may not directly apply to other GLP-1 RAs."},{"rthcId":"RPEP-09368","title":"Engineering PEG10assembled endogenous virus-like particles with genetically encoded neoantigen peptides for cancer vaccination.","authors":"Tang, Ruijing; Guo, Luobin; Wei, Tingyu; Chen, Tingting; Yang, Huan; Ye, Honghao; Lin, Fangzhou; Zeng, Yongyi; Yu, Haijun; Cai, Zhixiong; Liu, Xiaolong","year":2024,"journal":"eLife, 13","doi":"10.7554/eLife.98579","pmid":"39269893","tags":["peptide-vaccines","cancer-therapy","immune-system","drug-delivery"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"PEG10-based endogenous virus-like particles loaded with neoantigen peptides efficiently targeted dendritic cells, promoted their maturation, and induced neoantigen-specific T cell responses with significant antitumor efficacy in mouse liver cancer models.","whyItMatters":"Traditional virus-based vaccine delivery faces problems with immune neutralization. Using a human-derived capsid protein sidesteps this issue, potentially enabling more effective and repeatable cancer vaccine administration.","specificNumbers":"PEG10 is an endogenous human protein. Neoantigen peptides were genetically encoded into the VLP structure.","methodology":"Preclinical study engineering PEG10-based VLPs (ePAC) with genetically encoded neoantigens and CpG-ODN surface modification, tested in mouse orthotopic liver cancer and humanized tumor models combined with anti-TIM-3 therapy.","limitations":"Preclinical mouse data only — no human trials yet; liver cancer focus may not generalize to all tumor types; manufacturing scalability and clinical-grade production not addressed; humanized mouse models only approximate human immune responses."},{"rthcId":"RPEP-09369","title":"Personalized neoantigen hydrogel vaccine combined with PD-1 and CTLA-4 double blockade elicits antitumor response in liver metastases by activating intratumoral CD8+CD69+ T cells.","authors":"Tang, Shichuan; Tang, Ruijing; Chen, Geng; Zhang, Da; Lin, Kongying; Yang, Huan; Fu, Jun; Guo, Yutong; Lin, Fangzhou; Dong, Xiuqing; Huang, Tingfeng; Kong, Jie; Yin, Xiaowei; Ge, Aimin; Lin, Qizhu; Wu, Ming; Liu, Xiaolong; Zeng, Yongyi; Cai, Zhixiong","year":2024,"journal":"Journal for immunotherapy of cancer, 12(12)","doi":"10.1136/jitc-2024-009543","pmid":"39694701","tags":["peptide-vaccines","cancer-therapy","immune-system"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"NPT-gel neoantigen vaccine combined with PD-1/CTLA-4 dual blockade unlocked immunosuppressive liver metastasis microenvironment by inducing CD8+CD69+ T cell infiltration, showing superior antitumor efficacy in multiple preclinical models.","whyItMatters":"Liver metastases have extremely poor prognosis and resist most immunotherapies. This combination strategy addresses the fundamental challenge of the liver's immune-tolerant environment, potentially opening a new treatment approach for patients with limited options.","specificNumbers":"Combined neoantigen peptide hydrogel with anti-PD-1 and anti-CTLA-4 dual checkpoint blockade. Activated CD8+CD69+ T cells in tumors.","methodology":"Preclinical study using SEER database patient analysis plus multiple mouse liver metastasis models, testing neoantigen peptide hydrogel vaccine (NPT-gels) with Poly(I:C) and thymosin α-1 adjuvants combined with anti-PD-1/anti-CTLA-4 dual blockade.","limitations":"Preclinical mouse models only; no human clinical data yet; personalized neoantigen identification adds manufacturing complexity; hyaluronic acid hydrogel long-term safety not established in cancer context; liver metastasis models may not fully recapitulate human disease."},{"rthcId":"RPEP-09370","title":"Synthetic Collagen Hydrogels through Symmetric Self-Assembly of Small Peptides.","authors":"Tanrikulu, I Caglar; Dang, Lianna; Nelavelli, Lekha; Ellison, Aubrey J; Olsen, Bradley D; Jin, Song; Raines, Ronald T","year":2024,"journal":"Advanced science (Weinheim, Baden-Wurttemberg, Germany), 11(3), e2303228","doi":"10.1002/advs.202303228","pmid":"37997193","tags":["collagen-peptides","wound-healing","drug-delivery"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"33-residue collagen-mimetic peptides using SESSA design self-assembled into both nanofibers and hydrogels, with consistent behavior across scales and a direct structure-property relationship.","whyItMatters":"Synthetic collagen hydrogels could replace animal-sourced collagen in tissue engineering and regenerative medicine, eliminating risks of immune reactions, contamination, and batch-to-batch variability that limit current biomaterials.","specificNumbers":"Used SESSA strategy to overcome the design challenges of collagen's triple-helical structure. Created chemically defined hydrogels.","methodology":"Computational modeling of symmetric association states combined with experimental synthesis and characterization of collagen-mimetic peptide self-assemblies at molecular, nanofiber, and hydrogel scales.","limitations":"In vitro characterization only — no cell culture or tissue engineering validation reported; long-term stability and degradation properties not assessed; cost and scalability of peptide synthesis may limit practical applications; biocompatibility not tested in vivo."},{"rthcId":"RPEP-09371","title":"The first interim analysis of Italian patients enrolled in the real-world, Pan-European, prospective, observational, phase 4 PEARL study of fremanezumab effectiveness.","authors":"Tassorelli, Cristina; Barbanti, Piero; Finocchi, Cinzia; Geppetti, Pierangelo; Kokturk, Pinar; Russo, Antonio; Sacco, Simona; Cepparulo, Mario","year":2024,"journal":"Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 45(5), 2353-2363","doi":"10.1007/s10072-024-07357-3","pmid":"38424386","tags":["cgrp","clinical-trials","pain"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"65.1% of patients achieved ≥50% reduction in monthly migraine days at month 6, and approximately 80% met MIDAS-based Italian criteria for treatment continuation.","whyItMatters":"Italy has uniquely strict continuation criteria for CGRP antibodies requiring demonstrated disability improvement. This study shows that fremanezumab meets these real-world effectiveness thresholds, supporting its clinical and health-economic value.","specificNumbers":"Italian criteria: MIDAS score ≥11 at start, ≥50% MIDAS reduction at months 3 and 6 for renewal. Fremanezumab approved by AIFA in 2020.","methodology":"Interim analysis of the Italian cohort from PEARL, a pan-European prospective observational phase 4 study, including 318 episodic and chronic migraine patients treated with fremanezumab in routine clinical practice.","limitations":"Interim analysis without final results; no placebo control (observational design); Italian regulatory criteria may limit generalizability; potential selection bias toward treatment-responsive patients who continue therapy."},{"rthcId":"RPEP-09372","title":"ABCA7-dependent induction of neuropeptide Y is required for synaptic resilience in Alzheimer's disease through BDNF/NGFR signaling.","authors":"Tayran, Hüseyin; Yilmaz, Elanur; Bhattarai, Prabesh; Min, Yuhao; Wang, Xue; Ma, Yiyi; Wang, Ni; Jeong, Inyoung; Nelson, Nastasia; Kassara, Nada; Cosacak, Mehmet Ilyas; Dogru, Ruya Merve; Reyes-Dumeyer, Dolly; Stenersen, Jakob Mørkved; Reddy, Joseph S; Qiao, Min; Flaherty, Delaney; Gunasekaran, Tamil Iniyan; Yang, Zikun; Jurisch-Yaksi, Nathalie; Teich, Andrew F; Kanekiyo, Takahisa; Tosto, Giuseppe; Vardarajan, Badri N; İş, Özkan; Ertekin-Taner, Nilüfer; Mayeux, Richard; Kizil, Caghan","year":2024,"journal":"Cell genomics, 4(9), 100642","doi":"10.1016/j.xgen.2024.100642","pmid":"39216475","tags":["neuropeptides","brain-and-cognition","neuroprotection"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"ABCA7 loss suppresses neuropeptide Y expression, reducing BDNF and synaptic density — a mechanism directly linking this Alzheimer's risk gene to brain resilience through NPY-BDNF-NGFR signaling.","whyItMatters":"This study reveals a concrete molecular pathway connecting one of the top Alzheimer's risk genes to brain protection, opening potential therapeutic targets through neuropeptide Y supplementation or pathway modulation.","specificNumbers":"Used single-cell transcriptomics in heterozygous abca7+/- knockout zebrafish combined with Aβ42 toxicity models.","methodology":"CRISPR-Cas9 knockout zebrafish with single-cell transcriptomics, human iPSC-derived neurons exposed to Aβ42, and clinical correlation with human AD brain samples and genetic data.","limitations":"Zebrafish and iPSC-derived neuron models may not fully recapitulate human Alzheimer's pathology; clinical correlations are observational; causal pathway in humans not yet proven through intervention studies; NPY supplementation as therapy not tested."},{"rthcId":"RPEP-09373","title":"Reduced expression of central innate defense molecules in pancreatic biopsies from subjects with Type  1 diabetes.","authors":"Tegehall, Angie; Ingvast, Sofie; Krogvold, Lars; Dahl-Jørgensen, Knut; Korsgren, Olle","year":2024,"journal":"Acta diabetologica, 61(9), 1117-1127","doi":"10.1007/s00592-024-02286-1","pmid":"38717484","tags":["defensins","immune-system","type-1-diabetes"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Type 1 diabetes patients showed reduced or absent expression of defensins Beta-1, Alpha-1, Cathelicidin, and REG3A in the pancreas, decoupled from inflammation levels, unlike normal controls.","whyItMatters":"This is one of the first studies to characterize the defensin system in the diabetic pancreas, revealing a potential innate immune dysfunction that could contribute to disease pathogenesis and may open new therapeutic avenues.","specificNumbers":"Studied pancreases from non-diabetic donors of different ages and from subjects with different stages of type 1 diabetes.","methodology":"Immunohistochemical analysis of eight different defensins and immune cell markers (CD3+, CD45+, CD68+, NES+) across head, body, and tail sections of pancreases from non-diabetic donors of various ages and type 1 diabetes donors with varying disease duration.","limitations":"Small sample sizes typical of human pancreas studies (organ donor tissue is scarce); observational without mechanistic experiments to determine causality; unclear whether defensin loss is cause or consequence of the disease process."},{"rthcId":"RPEP-09374","title":"Role of glucagon-like peptide-1 agonists in obesity and heart failure with preserved ejection fraction.","authors":"Temporelli, Pier Luigi","year":2024,"journal":"European heart journal supplements : journal of the European Society of Cardiology, 26(Suppl 1), i127-i130","doi":"10.1093/eurheartjsupp/suae011","pmid":"38867875","tags":["glp-1-receptor-agonists","semaglutide","cardiovascular-health","weight-management"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"STEP-HFpEF trial: semaglutide significantly improved quality of life, weight, 6-minute walk distance, CRP (30-40% reduction), and NT-proBNP levels in 529 obese HFpEF patients over 52 weeks.","whyItMatters":"HFpEF is the most common form of heart failure and has lacked effective treatments beyond managing symptoms. Semaglutide may address the underlying obesity-inflammation axis driving HFpEF, representing a potential disease-modifying therapy.","specificNumbers":"HFpEF is the majority of community heart failure. STEP trials showed 30-40% C-reactive protein reduction with semaglutide.","methodology":"Narrative review summarizing key clinical trial evidence (STEP trials, STEP-HFpEF, SELECT) for GLP-1 agonists in obesity-related heart failure with preserved ejection fraction.","limitations":"Review format without systematic methodology; STEP-HFpEF excluded diabetic patients; 52-week duration may not capture long-term outcomes; semaglutide's HFpEF benefits may be partially mediated through weight loss alone."},{"rthcId":"RPEP-09375","title":"Revamped mini-αA-crystallin showed improved skin permeation and therapeutic activity against melittin-induced toxicity.","authors":"Tender, Tenzin; Rahangdale, Rakesh Ravishankar; Nampoothiri, Madhavan; Raychaudhuri, Ruchira; Mutalik, Srinivas; Sharma, Krishna; Chandrashekar H, Raghu","year":2024,"journal":"Toxicon : official journal of the International Society on Toxinology, 239, 107611","doi":"10.1016/j.toxicon.2024.107611","pmid":"38211805","tags":["bioactive-peptides","venom-derived-peptides","drug-delivery"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"MAC-GRD gel showed superior skin permeation and outperformed both native MAC and 1% hydrocortisone in anti-inflammatory (paw thickness), analgesic (writhing reduction), and antioxidant (GSH/MDA) activity against melittin toxicity.","whyItMatters":"Severe bee stings lack specific treatments. This peptide-based approach offers a targeted therapy that outperforms current standard care (hydrocortisone), with potential for development as a dedicated bee sting treatment.","specificNumbers":"Melittin causes haemolysis, rhabdomyolysis, and renal failure. Modified peptide showed improved skin permeation over the original.","methodology":"Ex-vivo skin permeation study using Franz diffusion cells, followed by in-vivo preclinical experiments in Wistar rats measuring writhing response, paw inflammation, and oxidative stress biomarkers (GSH, MDA) against melittin-induced toxicity.","limitations":"Animal study only (Wistar rats); small group sizes; topical gel formulation may have limited penetration for systemic melittin effects; bee sting clinical scenarios are more complex than isolated melittin injection; no human safety or efficacy data."},{"rthcId":"RPEP-09376","title":"Evaluation and comparison of efficacy and safety of tirzepatide, liraglutide and SGLT2i in patients with type 2 diabetes mellitus: a network meta-analysis.","authors":"Teng, Yunjie; Fan, Xue; Yu, Rui; Yang, Xiaoping","year":2024,"journal":"BMC endocrine disorders, 24(1), 278","doi":"10.1186/s12902-024-01805-z","pmid":"39719583","tags":["glp-1-receptor-agonists","type-2-diabetes","clinical-trials"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Tirzepatide 15 mg reduced HbA1c by 2.24% and weight by 8.74 kg vs placebo — the most effective of all seven medications. Liraglutide outperformed SGLT2i for glycemia; SGLT2i excelled in blood pressure.","whyItMatters":"This is one of the first comprehensive network comparisons of tirzepatide against both GLP-1 agonists and SGLT2 inhibitors, helping clinicians choose the right medication based on each patient's primary treatment goals.","specificNumbers":"Compared: tirzepatide, liraglutide, canagliflozin, ertugliflozin, empagliflozin, dapagliflozin, and henagliflozin. Searched through February 2024.","methodology":"Bayesian network meta-analysis of 28 randomized controlled trials (8,499 participants) comparing tirzepatide (5/10/15 mg), liraglutide (1.2/1.8 mg), and five SGLT2 inhibitors for HbA1c, weight, blood pressure, and safety outcomes.","limitations":"Network meta-analysis relies on indirect comparisons; trial populations differed; only studied as monotherapy add-ons (not combinations); short-term outcomes may not capture long-term cardiovascular benefits; SGLT2i cardiac and renal protection not captured by these endpoints."},{"rthcId":"RPEP-09377","title":"Cost-Effectiveness Evaluation of Oral CGRP Antagonists, Atogepant and Rimegepant, for the Preventative Treatment of Episodic Migraine: Results from a US Societal Perspective Model.","authors":"Thaliffdeen, Ryan; Yu, Anthony; Rascati, Karen","year":2024,"journal":"Clinical drug investigation, 44(3), 209-217","doi":"10.1007/s40261-024-01345-3","pmid":"38381352","tags":["cgrp","clinical-trials"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Atogepant ICER: >$450,000/QALY; rimegepant ICER: >$890,000/QALY — both far exceeding the $150,000/QALY cost-effectiveness threshold. Drug acquisition cost was the dominant factor.","whyItMatters":"Despite proven efficacy, oral CGRP antagonists may face reimbursement and access challenges if their cost-effectiveness remains poor. This analysis highlights the need for price reductions or better patient selection to justify their use.","specificNumbers":"Atogepant 60 mg and rimegepant 75 mg compared to placebo. 1-year time horizon. US societal perspective.","methodology":"Decision tree model with 1-year time horizon from US societal perspective, simulating patient cohorts using trial-reported baseline and change-from-baseline monthly migraine days. Each drug compared to its own trial's placebo group.","limitations":"Each drug compared to its own trial's placebo (no direct comparison between drugs); 1-year horizon may not capture long-term benefits; indirect costs difficult to quantify precisely; societal perspective may differ from payer perspective; no comparison to injectable CGRP antibodies."},{"rthcId":"RPEP-09378","title":"Treatment and Long-Term Safety Outcomes of Peptide Receptor Radionuclide Therapy for Metastatic Neuroendocrine Tumours: An Asian Experience.","authors":"Tham, Wei Ying; Huang, Hian Liang; Tai, David Wai Meng; Allen, John C; Hwang, Jacqueline S G; Loh, Lih Ming; Goh, Brian K P; Ong, Simon Y K; Kek, Peng Chin; Tan, Damien M Y; Ng, David C E; Loke, Kelvin S H","year":2024,"journal":"Neuroendocrinology, 114(9), 840-847","doi":"10.1159/000538523","pmid":"38531329","tags":["somatostatin-analogs","cancer-therapy","radionuclide-therapy","clinical-trials"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"37.9% partial/complete response rate, 49-month median progression-free survival, with 9% grade 3+ hematological toxicity and 4% grade 3/4 hepatobiliary toxicity in 107 Asian NET patients.","whyItMatters":"This is one of the largest Asian PRRT datasets, addressing the evidence gap for this population. Epidemiological differences in NETs between populations make population-specific efficacy data essential for clinical decision-making.","specificNumbers":"Data from an Asian center. Previous evidence primarily from US, Europe, and Australia.","methodology":"Retrospective analysis of 107 patients with metastatic neuroendocrine tumors who underwent PRRT from January 2012 to March 2019, with response assessment using RECIST 1.1 criteria and qualitative analysis.","limitations":"Retrospective single-center design; heterogeneous tumor types and grades within the cohort; variable number of treatment cycles; liver metastases confounded hepatobiliary toxicity assessment; no randomized comparator."},{"rthcId":"RPEP-09379","title":"Antimicrobial peptides and other potential biomarkers of critical illness in SARS-CoV-2 patients with acute kidney injury. AMPAKI-CoV study.","authors":"Theotonio Dos Santos, Lucas Ferreira; Barbeiro, Hermes Vieira; Barbeiro, Denise Frediani; de Souza, Heraldo Possolo; Pinheiro da Silva, Fabiano","year":2024,"journal":"Physiological reports, 12(3), e15945","doi":"10.14814/phy2.15945","pmid":"38328863","tags":["antimicrobial-peptides","defensins","immune-system","diagnostics"],"studyType":"cohort","evidenceStrength":"preliminary","keyFinding":"α-defensin 1 and α-defensin 3 were significantly elevated in COVID-19 patients with AKI vs without AKI, and IL-10/IL-10×IL-1B showed excellent AKI discrimination (AUC 0.86-0.88).","whyItMatters":"Understanding the role of antimicrobial peptides in COVID-19 organ damage could reveal new biomarkers for early kidney injury detection and potential therapeutic targets to prevent AKI in severe infections.","specificNumbers":"Five AMPs measured: LL-37, α-defensin 1, α-defensin 3, β-defensin 1, and β-defensin 2. Over 300 AMPs described in mammals total.","methodology":"Cross-sectional observational study measuring five AMPs (ELISA) and six cytokines (Milliplex bead immunoassay) in three groups: 15 healthy controls, 36 COVID-19 without AKI, and 17 COVID-19 with AKI.","limitations":"Small sample sizes (especially AKI group, n=17); cross-sectional design cannot establish causality; single-center study; COVID-19 severity differences between groups may confound AMP comparisons; no longitudinal tracking of AMP levels."},{"rthcId":"RPEP-09380","title":"Collagen peptide supplementation before bedtime reduces sleep fragmentation and improves cognitive function in physically active males with sleep complaints.","authors":"Thomas, Craig; Kingshott, Ruth N; Allott, Kirsty M; Tang, Jonathan C Y; Dunn, Rachel; Fraser, William D; Thorley, Josh; Virgilio, Nicolina; Prawitt, Janne; Hogervorst, Eef; Škarabot, Jakob; Clifford, Tom","year":2024,"journal":"European journal of nutrition, 63(1), 323-335","doi":"10.1007/s00394-023-03267-w","pmid":"37874350","tags":["collagen-peptides","sleep-and-recovery","brain-and-cognition"],"studyType":"RCT","evidenceStrength":"moderate","keyFinding":"Collagen peptides reduced polysomnographic awakenings from 29.3 to 21.3 per night and improved next-morning Stroop test accuracy to 100% vs 97% with placebo.","whyItMatters":"Sleep disruption is extremely common among active individuals and has cascading effects on recovery and cognitive performance. This study suggests a simple, well-tolerated nutritional intervention may help reduce sleep fragmentation.","specificNumbers":"13 males, age 24±4 years, training 7±3 hours/week, Athens Insomnia Scale score 9±2. Dose: 15 g collagen peptides daily for 7 nights.","methodology":"Randomized, crossover design with 13 athletic males taking 15g collagen peptides or placebo before bed for 7 nights, measured with polysomnography, actigraphy, sleep diaries, cognitive tests, core temperature, and inflammatory/endocrine markers.","limitations":"Very small sample size (13 men); only male athletes studied; short 7-night protocol; cognitive improvement was modest and limited to one test; no glycine-only comparison to isolate the active component; crossover washout period only 7 days."},{"rthcId":"RPEP-09381","title":"The dual GCGR/GLP-1R agonist survodutide: Biomarkers and pharmacological profiling for clinical candidate selection.","authors":"Thomas, Leo; Martel, Eric; Rist, Wolfgang; Uphues, Ingo; Hamprecht, Dieter; Neubauer, Heike; Augustin, Robert","year":2024,"journal":"Diabetes, obesity & metabolism, 26(6), 2368-2378","doi":"10.1111/dom.15551","pmid":"38560764","tags":["glp-1-receptor-agonists","glucagon","weight-management","drug-delivery"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Survodutide achieved 25% body weight reduction in DIO mice (exceeding semaglutide's GLP-1-only approach) while maintaining comparable antidiabetic efficacy, earning selection from 19 candidates for Phase 3 trials.","whyItMatters":"Dual-receptor agonists represent the next frontier in obesity treatment, potentially exceeding the already impressive results of GLP-1-only drugs like semaglutide. Understanding how survodutide was selected reveals the rational drug design process behind these breakthroughs.","specificNumbers":"19 dual agonists screened. 3 selected for in-depth profiling. Survodutide (BI 456906) chosen as clinical candidate.","methodology":"Systematic biomarker-driven screening of 19 dual GCGR/GLP-1R agonists using in vitro cAMP assays, in vivo target engagement biomarkers (FGF21, NNMT), oral glucose tolerance, and efficacy studies in DIO and db/db mice.","limitations":"Preclinical data in mice — human pharmacology may differ; DIO mice don't perfectly model human obesity; acute biomarker engagement may not predict chronic efficacy; Phase 3 trial results not yet available; comparison to semaglutide was at single time points."},{"rthcId":"RPEP-09382","title":"Building the Glucagon-Like Peptide-1 Receptor Brick by Brick: Revisiting a 1993 Diabetes Classic by Thorens et al.","authors":"Thorens, Bernard; Hodson, David J","year":2024,"journal":"Diabetes, 73(7), 1027-1031","doi":"10.2337/dbi24-0025","pmid":"38900951","tags":["glp-1-receptor-agonists","exendin-4"],"studyType":"review","evidenceStrength":"strong","keyFinding":"The 1993 cloning of the human GLP-1 receptor and identification of exendin-4 as its agonist established the molecular foundation for all subsequent GLP-1R drug development.","whyItMatters":"Understanding the origins of GLP-1 receptor biology provides essential context for the current obesity treatment revolution and highlights how basic science discovery translates into life-changing therapies decades later.","specificNumbers":"GLP-1R is a class B G protein-coupled receptor. Exendin-4(1-39) was identified as a potent agonist. Original paper published in Diabetes, 1993.","methodology":"Historical perspective and review article revisiting the original 1993 Diabetes paper by Thorens et al., tracing its influence across multiple research disciplines over three decades.","limitations":"Perspective article rather than primary research; necessarily selective in coverage of three decades of research; focused on GLP-1R biology without comprehensive comparison to other emerging targets."},{"rthcId":"RPEP-09383","title":"Mechanistic study of acupuncture on the pterygopalatine ganglion to improve allergic rhinitis: analysis of multi-target effects based on bioinformatics/network topology strategie.","authors":"Tian, Meihui; Sun, Weifang; Mao, Yinhui; Zhang, Yanan; Liu, Huan; Tang, Yong","year":2024,"journal":"Briefings in bioinformatics, 25(4)","doi":"10.1093/bib/bbae287","pmid":"38877888","tags":["neuropeptides","inflammation"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Acupuncture at the pterygopalatine ganglion decreased serum substance P and elevated neuropeptide Y in allergic rhinitis rats, with effects mediated through TLR4/NF-kB/NLRP3 pathway inhibition.","whyItMatters":"Understanding how acupuncture modulates neuropeptide levels provides molecular evidence for its mechanism of action in allergic rhinitis and could inform both traditional and peptide-based therapeutic approaches.","specificNumbers":"Multiple molecular targets identified through network analysis and text mining.","methodology":"Combined bioinformatics/network topology analysis (16 biomarkers, 108 protein targets, 135 KEGG pathways) with in vivo validation using OVA-induced allergic rhinitis rat model.","limitations":"Animal model only (OVA-induced rat AR); bioinformatics predictions require further experimental validation; single acupuncture technique studied; no dose-response or frequency optimization; neuropeptide changes measured only in serum, not locally."},{"rthcId":"RPEP-09384","title":"Role of glucagon-like peptide-1 receptor agonists in the treatment of obesity, cardiovascular disease, and cerebrovascular disease.","authors":"Tirandi, Amedeo; Montecucco, Fabrizio; Carbone, Federico; Liberale, Luca","year":2024,"journal":"Polish archives of internal medicine, 134(2)","doi":"10.20452/pamw.16658","pmid":"38226456","tags":["glp-1-receptor-agonists","weight-management","cardiovascular-health","brain-and-cognition"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Substance P is altered in ALS patients and may play a neuroprotective role by inhibiting excitotoxicity-induced motor neuron death, potentially contributing to the selective sparing of certain motor neuron populations.","whyItMatters":"ALS has no cure and limited treatment options. Understanding why certain motor neurons resist degeneration could reveal new therapeutic targets, and substance P's potential neuroprotective role opens a novel avenue for drug development.","specificNumbers":"Worldwide obesity prevalence is increasing dramatically with significant economic burden.","methodology":"Narrative review synthesizing clinical data on SP levels in ALS patients, preclinical studies of SP's neuroprotective effects, and mechanistic studies of SP's role in motor neuron excitability and survival.","limitations":"Review article synthesizing observational and preclinical data; causal relationship between SP levels and motor neuron protection not definitively established; SP has multiple functions throughout the nervous system complicating therapeutic targeting; no clinical trials of SP-based ALS therapies reported."},{"rthcId":"RPEP-09385","title":"Perspective role of Substance P in Amyotrophic Lateral Sclerosis: From neuronal vulnerability to neuroprotection.","authors":"Tirassa, Paola; Rosso, Pamela; Fico, Elena; Marenco, Marco; Mallone, Fabiana; Gharbiya, Magda; Lambiase, Alessandro; Severini, Cinzia","year":2024,"journal":"Neuroscience and biobehavioral reviews, 167, 105914","doi":"10.1016/j.neubiorev.2024.105914","pmid":"39374680","tags":["neuropeptides","neuroprotection","brain-and-cognition"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Elevated BNP and NT-proBNP levels in diabetes patients correlate with cardiac abnormalities and can be used for heart failure risk stratification and potentially for guiding treatment strategies.","whyItMatters":"Heart failure is one of the most serious and common complications of diabetes. Natriuretic peptide testing offers a relatively simple blood test that can help identify at-risk patients early and guide treatment intensity.","specificNumbers":"Altered SP levels detected in brain, spinal cord, and cerebrospinal fluid of ALS patients and preclinical models.","methodology":"Narrative review synthesizing evidence on natriuretic peptide biology, diagnostic utility, and therapeutic guidance potential in the context of diabetes and heart failure.","limitations":"Review article without new primary data; NP-guided therapy evidence is still evolving; NP levels can be influenced by factors beyond cardiac function (obesity, kidney disease); lacks specific treatment algorithms; focused primarily on type 2 diabetes."},{"rthcId":"RPEP-09386","title":"Emerging Role of Natriuretic Peptides in Diabetes Care: A Brief Review of Pertinent Recent Literature.","authors":"Tiwari, Dipti; Aw, Tar Choon","year":2024,"journal":"Diagnostics (Basel, Switzerland), 14(19)","doi":"10.3390/diagnostics14192251","pmid":"39410655","tags":["natriuretic-peptides","cardiovascular-health","type-2-diabetes","diagnostics"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"SP and NPY promoted salivary gland branching morphogenesis in aging klotho-deficient mice through FGF/FGFR/ERK1/2 signaling, rescuing the developmental deficits caused by neuronal dysfunction.","whyItMatters":"Dry mouth (xerostomia) is a major quality-of-life issue in aging populations. Understanding how neuropeptides regulate salivary gland development and maintenance could lead to therapies for age-related salivary dysfunction.","specificNumbers":"Diabetes markedly increases cardiovascular event susceptibility. Elevated BNP/NT-proBNP correlate with cardiac structural and functional abnormalities.","methodology":"In vitro embryonic salivary gland culture from klotho-deficient (Kl-/-) mice with SP/NPY treatment, morphological analysis, immunostaining, RNA-seq profiling, and pathway inhibition studies (ERK inhibitor U0126, FGFR inhibitor BGJ389).","limitations":"Mouse model using klotho-deficiency (accelerated aging) may not fully represent natural human aging; in vitro organ culture conditions differ from in vivo; focused on embryonic development rather than adult gland regeneration; no human tissue validation."},{"rthcId":"RPEP-09387","title":"Neuropeptides regulate embryonic salivary gland branching through the FGF/FGFR pathway in aging klotho-deficient mice.","authors":"Toan, Nguyen Khanh; Kim, Soo-A; Ahn, Sang-Gun","year":2024,"journal":"Aging cell, 23(12), e14329","doi":"10.1111/acel.14329","pmid":"39239870","tags":["neuropeptides","aging","hormones-and-signaling"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Substance P and neuropeptide Y regulated embryonic salivary gland branching morphogenesis through the FGF/FGFR pathway in klotho-deficient accelerated aging mice.","whyItMatters":"Understanding how neuropeptides affect organ development during aging could lead to treatments for dry mouth and other age-related gland dysfunction.","specificNumbers":"Klotho-deficient (Kl-/-) mice used as accelerated aging model. Both substance P and NPY effects on FGF/FGFR signaling examined.","methodology":"Animal study examining neuropeptide effects on salivary gland branching morphogenesis in embryonic klotho-knockout mice using morphological analysis and immunostaining.","limitations":"Mouse model of accelerated aging may not perfectly represent normal aging. Embryonic findings may not directly apply to adult gland function."},{"rthcId":"RPEP-09388","title":"A review of serious adverse events linked with GLP-1 agonists in type 2 diabetes mellitus and obesity treatment.","authors":"Tobaiqy, Mansour","year":2024,"journal":"Pharmacological reports : PR, 76(5), 981-990","doi":"10.1007/s43440-024-00629-x","pmid":"39093550","tags":["glp-1-receptor-agonists","safety-and-side-effects"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Evidence for serious adverse events with GLP-1 agonists is mixed across all categories — anaphylaxis, cardiovascular, GI, psychiatric, and thyroid events have been reported in some studies but not confirmed in others.","whyItMatters":"With tens of millions of people now using GLP-1 medications, understanding their serious adverse event profile is critical for informed clinical decision-making and patient safety monitoring.","specificNumbers":"Literature search from 2010 onward. Covers all reported serious adverse events across the GLP-1 drug class.","methodology":"Narrative review of 22 articles (5 case reports, 5 RCTs, 9 real-world cohort analyses, 2 meta-analyses, 1 systematic review and meta-analysis) from PubMed, Google Scholar, and Embase from 2010 onwards.","limitations":"Narrative review without systematic methodology or meta-analysis; heterogeneous study designs limit comparison; publication bias may affect reported associations; rapidly evolving literature means some newer safety data may not be captured."},{"rthcId":"RPEP-09389","title":"Protease-activated CendR peptides targeting tenascin-C: mitigating off-target tissue accumulation.","authors":"Tobi, Allan; Haugas, Maarja; Rabi, Kristina; Sethi, Jhalak; Põšnograjeva, Kristina; Paiste, Päärn; Jagomäe, Toomas; Pleiko, Karlis; Lingasamy, Prakash; Teesalu, Tambet","year":2024,"journal":"Drug delivery and translational research, 14(10), 2945-2961","doi":"10.1007/s13346-024-01670-2","pmid":"39012578","tags":["cell-penetrating-peptides","cancer-therapy","drug-delivery"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Two novel peptides (PL3uCendR and SKLG) bind tenascin-C constitutively but only activate NRP-1 binding after uPA cleavage, reducing off-target tissue accumulation while maintaining tumor penetration.","whyItMatters":"Off-target toxicity is a major challenge for peptide-drug conjugates and targeted nanoparticles. Protease-activated peptides that only engage their tumor-penetrating function in the tumor microenvironment could dramatically improve the therapeutic window of cancer nanomedicines.","specificNumbers":"PL3 peptide (AGRGRLVR) was modified for protease activation. Off-target lung accumulation was significantly reduced.","methodology":"Rational design and uPA-treated phage library screening on recombinant NRP-1, validated with in vitro cleavage/binding/internalization assays and in vivo biodistribution in orthotopic glioblastoma mice.","limitations":"Preclinical mouse data only; glioblastoma model may not generalize to all tumor types; uPA expression varies across cancers; peptide stability and pharmacokinetics in humans not established; no drug payload attached for therapeutic efficacy testing."},{"rthcId":"RPEP-09390","title":"5-Hydroxypyrroloindoline Affords Tryptathionine and 2,2'-bis-Indole Peptide Staples: Application to Melanotan-II.","authors":"Todorovic, Mihajlo; Blanc, Antoine; Wang, Zhou; Lozada, Jerome; Froelich, Juliette; Zeisler, Jutta; Zhang, Chengcheng; Merkens, Helen; Benard, Francois; Perrin, David M","year":2024,"journal":"Chemistry (Weinheim an der Bergstrasse, Germany), 30(19), e202304270","doi":"10.1002/chem.202304270","pmid":"38285527","tags":["melanocortin-peptides","drug-delivery","bioactive-peptides"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Both tryptathionine and 2,2'-bis-indole stapling of α-MSH produced nanomolar Ki values, with one stapled variant achieving sub-nanomolar affinity for melanocortin receptors.","whyItMatters":"Peptide stapling is key to making peptide drugs more stable and cell-penetrating. These new staple types from natural product chemistry expand the peptide drug designer's toolkit and could enable development of more potent, stable therapeutic peptides.","specificNumbers":"Two new staple types developed: tryptathionine (from amatoxins/phallotoxins) and 2,2'-bis-indole (from staurosporine). Applied to melanotan-II.","methodology":"Chemical synthesis using 5-hydroxypyrroloindoline condensation with cysteine-thiol or tryptophan-indole, applied to α-MSH as a model peptide, with binding affinity measured against melanocortin receptors.","limitations":"Demonstrated on only one model peptide (α-MSH); binding affinity measured but not cellular activity or in vivo efficacy; metabolic stability of stapled peptides not assessed; limited exploration of staple position effects; no comparison to existing stapling methods."},{"rthcId":"RPEP-09391","title":"Dexamethasone phosphate and penetratin co-eluting contact lenses: a strategy to enhance ocular drug permeability.","authors":"Toffoletto, Nadia; Salema-Oom, Madalena; Nicoli, Sara; Pescina, Silvia; González-Fernández, Felipe M; Pinto, Carlos A; Saraiva, Jorge A; Alves de Matos, António P; Vivero-Lopez, Maria; Huete-Toral, Fernando; Carracedo, Gonzalo; Saramago, Benilde; Serro, Ana Paula","year":2024,"journal":"International journal of pharmaceutics, 650, 123685","doi":"10.1016/j.ijpharm.2023.123685","pmid":"38072146","tags":["cell-penetrating-peptides","drug-delivery"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Co-delivery of dexamethasone with penetratin from contact lenses significantly increased drug concentrations in the cornea and aqueous humor after 6 hours of wear in rabbits.","whyItMatters":"Getting drugs past the eye's tissue barriers to treat conditions like macular degeneration or uveitis is a major clinical challenge. Cell-penetrating peptides in contact lenses could offer a non-invasive alternative to eye injections.","specificNumbers":"Co-released dexamethasone sodium phosphate and penetratin (cell-penetrating peptide) from contact lens platform.","methodology":"Development and characterization of HEMA-based hydrogel contact lenses functionalized with AAc and/or APMA, with in vitro release kinetics, biocompatibility testing, and in vivo ocular distribution in rabbits after 6 hours of CL wearing.","limitations":"Rabbit eye model may not fully predict human ocular drug distribution; only one drug-peptide combination tested; long-term safety of repeated penetratin exposure to ocular tissues unknown; posterior segment drug levels not specifically measured; small animal study."},{"rthcId":"RPEP-09392","title":"The effect of prenatal fumonisin B exposure on bone innervation in newborn Wistar rats.","authors":"Tomaszewska, Ewa; Dobrowolski, Piotr; Dajnowska, Aleksandra; Arbatowska, Liwia; Puzio, Iwona; Rudyk, Halyna; Brezvyn, Oksana; Kotsyumbas, Ihor; Donaldson, Janine; Śliwa, Jadwiga; Arciszewski, Marcin B; Muszyński, Siemowit","year":2024,"journal":"Journal of veterinary research, 68(4), 633-642","doi":"10.2478/jvetres-2024-0056","pmid":"39776677","tags":["neuropeptides","bone-and-joint-health"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Prenatal fumonisin B exposure disrupted neuropeptide-containing bone nerve networks, decreasing galanin and VIP-positive fibers in both dose groups while paradoxically increasing overall network complexity at the higher dose.","whyItMatters":"Fumonisins are common food contaminants in cereals. Understanding their effects on the neuropeptide-mediated bone nerve system during prenatal development highlights a previously unrecognized risk pathway for bone development disorders.","specificNumbers":"6 pregnant rats per group; 3 groups (control, 60 mg/kg, 90 mg/kg fumonisin B); exposure from gestational day 7 to birth; one male pup per litter analyzed (n=6 per group).","methodology":"Controlled animal study with pregnant Wistar rats (n=6/group) exposed to fumonisin B at 60 or 90 mg/kg from gestation day 7 to birth, with immunohistochemistry analysis of bone innervation patterns (PGP 9.5, TH, ChAT, VIP, substance P, CART) in newborn femurs.","limitations":"Animal model may not directly translate to human prenatal exposure; only examined femur bones; short-term neonatal assessment without long-term bone health follow-up; high fumonisin doses may not reflect typical human dietary exposure; small sample sizes."},{"rthcId":"RPEP-09393","title":"Social functioning predicts individual changes in EEG microstates following intranasal oxytocin administration: A double-blind, cross-over randomized clinical trial.","authors":"Tomescu, Miralena I; Van der Donck, Stephanie; Perisanu, Emanuela M; Berceanu, Alexandru I; Alaerts, Kaat; Boets, Bart; Carcea, Ioana","year":2024,"journal":"Psychophysiology, 61(8), e14581","doi":"10.1111/psyp.14581","pmid":"38594888","tags":["oxytocin","brain-and-cognition"],"studyType":"RCT","evidenceStrength":"moderate","keyFinding":"Social functioning traits predicted how intranasal oxytocin changed brain network dynamics — higher social function increased visual network microstates while lower social function increased salience network microstates.","whyItMatters":"Understanding why oxytocin works differently for different people is critical for its potential use as a therapy for autism and other social disorders — this study shows baseline social functioning is a key predictor of response.","specificNumbers":"61 healthy male participants; double-blind crossover design; single-dose intranasal oxytocin; EEG recorded before and after administration.","methodology":"Double-blinded, randomized, placebo-controlled, cross-over study in 30 healthy young adult men, using EEG microstate analysis across specific spectral bands with multivariate partial least square statistics.","limitations":"Only 30 male participants; single-dose design may not reflect chronic administration; EEG microstates are indirect measures of network activity; social functioning measured by self-report; no female participants or clinical populations studied."},{"rthcId":"RPEP-09394","title":"Use of a Cyclic α-Alkylidene-β-Diketone as a Cleavable Linker Strategy for Antibody-Drug Conjugates.","authors":"Tong, Juliana T W; Sarwar, Makhdoom; Ahangarpour, Marzieh; Hume, Paul A; Williams, Geoffrey M; Brimble, Margaret A; Kavianinia, Iman","year":2024,"journal":"Journal of the American Chemical Society, 146(34), 23717-23728","doi":"10.1021/jacs.4c04567","pmid":"39143910","tags":["drug-delivery-systems","peptide-drug-conjugates"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"A cyclic α-alkylidene-β-diketone linker with azido trigger provides selective intracellular drug release, demonstrated through EGFR-targeting peptide-drug and antibody-drug conjugates.","whyItMatters":"ADCs are among the fastest-growing classes of cancer therapy. Better linker chemistry directly translates to safer, more effective treatments by ensuring drugs stay attached during circulation but release efficiently inside tumor cells.","specificNumbers":"Study explored Dde-based linker chemistry for ADC construction (specific numerical results not provided in abstract excerpt).","methodology":"Chemical synthesis and characterization of Dde-based cleavable linker, conjugation to EGFR-targeting peptide and antibody, with assessment of stability and release under reducing conditions.","limitations":"In vitro characterization without in vivo efficacy or toxicity data; single target (EGFR) tested; comparative advantage over existing linkers (Val-Cit, SMCC) not quantified; scalability and manufacturing considerations not addressed."},{"rthcId":"RPEP-09395","title":"Lentils protein isolate as a fermenting substrate for the production of bioactive peptides by lactic acid bacteria and neglected yeast species.","authors":"Tonini, Stefano; Tlais, Ali Zein Alabiden; Galli, Bruno Domingues; Helal, Ahmed; Tagliazucchi, Davide; Filannino, Pasquale; Zannini, Emanuele; Gobbetti, Marco; Di Cagno, Raffaella","year":2024,"journal":"Microbial biotechnology, 17(1), e14387","doi":"10.1111/1751-7915.14387","pmid":"38263855","tags":["food-derived-peptides","ace-inhibitory-peptides","antioxidant-peptides"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"H. uvarum SY1 fermentation of red lentil protein produced the highest abundance of bioactive peptides with antioxidant and ACE-inhibitory activities, including 12 fermentation-specific and 2 novel peptide sequences.","whyItMatters":"Plant-based protein sources are increasingly popular, and discovering that fermentation can generate health-promoting peptides from lentils adds nutritional value beyond basic protein content, supporting the development of functional plant-based foods.","specificNumbers":"H. uvarum SY1 and F. sanfranciscensis E10 were the most proteolytic. H. uvarum SY1 produced the highest antiradical and ACE-inhibitory activities among all tested strains.","methodology":"In vitro fermentation of red lentil protein isolate with lactic acid bacteria and yeast strains, followed by peptidomics analysis (2,039 sequences), BIOPEP-UWM database screening, and functional activity assays (antiradical, ACE-inhibitory, antifungal).","limitations":"In vitro activity assays may not translate to in vivo bioavailability and efficacy; peptide stability through digestion not assessed; novel peptide activities need validation; single lentil variety tested; functional activities measured in extracts, not individual peptides."},{"rthcId":"RPEP-09396","title":"Liraglutide Pretreatment Does Not Improve Acute Doxorubicin-Induced Cardiotoxicity in Rats.","authors":"Tonon, Carolina R; Monte, Marina G; Balin, Paola S; Fujimori, Anderson S S; Ribeiro, Ana Paula D; Ferreira, Natália F; Vieira, Nayane M; Cabral, Ronny P; Okoshi, Marina P; Okoshi, Katashi; Zornoff, Leonardo A M; Minicucci, Marcos F; Paiva, Sergio A R; Gomes, Mariana J; Polegato, Bertha F","year":2024,"journal":"International journal of molecular sciences, 25(11)","doi":"10.3390/ijms25115833","pmid":"38892020","tags":["glp-1-receptor-agonists","heart-health","liraglutide"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"Liraglutide pretreatment (0.6 mg/kg daily for 2 weeks) did not improve any echocardiographic, functional, or molecular measure of doxorubicin-induced acute cardiotoxicity in rats.","whyItMatters":"This negative result is important — it tempers enthusiasm about repurposing GLP-1 agonists as cardioprotective agents during cancer chemotherapy and highlights that GLP-1's known anti-inflammatory effects don't necessarily translate to all types of cardiac injury.","specificNumbers":"60 male Wistar rats; 4 groups (15 per group); control, doxorubicin alone, liraglutide alone, doxorubicin + liraglutide.","methodology":"Controlled animal study with 60 male Wistar rats in four groups (Control, Doxorubicin, Liraglutide, Doxorubicin+Liraglutide), with echocardiography, isolated heart studies, and myocardial protein expression analysis 48 hours after doxorubicin.","limitations":"Acute single-dose doxorubicin model may not represent clinical protocols (which use multiple lower doses); only one liraglutide dose tested; 2-week pretreatment may be insufficient; rat model may not predict human response; 48-hour endpoint may miss delayed protective effects."},{"rthcId":"RPEP-09397","title":"Evaluation of Pro-BNP biomarker in heart failure patients and its relationship with complete blood count parameters: A case-control study.","authors":"Torfi, Ekhlas; Bahreiny, Seyed S; Saki, Najmaldin; Khademi, Reyhane; Sarbazjoda, Ehsan; Nezhad, Inas A; Aghaei, Mojtaba","year":2024,"journal":"Health science reports, 7(9), e70083","doi":"10.1002/hsr2.70083","pmid":"39328979","tags":["natriuretic-peptides","heart-health","biomarkers-and-diagnostics"],"studyType":"cohort","evidenceStrength":"preliminary","keyFinding":"Heart failure patients had 2.4× higher Pro-BNP (2,500 vs 1,053 pg/mL) with significant associations to RDW, MCV, and platelet parameters, supporting combined biomarker approaches for HF diagnosis.","whyItMatters":"Heart failure diagnosis often relies on expensive specialized tests. Discovering that common, inexpensive blood count parameters correlate with Pro-BNP could make heart failure screening more accessible, especially in resource-limited settings.","specificNumbers":"89 participants total; 49 heart failure patients; 40 healthy controls.","methodology":"Case-control study of 89 participants (42 HF patients, 47 controls) comparing Pro-BNP levels alongside comprehensive CBC parameters with statistical analyses of associations.","limitations":"Small sample size (89 total); case-control design cannot establish causality; single-center study; Pro-BNP cutoff values not defined for this population; potential confounding from medications and comorbidities not fully controlled."},{"rthcId":"RPEP-09398","title":"TRESK channel activation ameliorates migraine-like pain via modulation of CGRP release from the trigeminovascular system and meningeal mast cells in experimental migraine models.","authors":"Torun, Ibrahim Ethem; Kilinc, Yasemin Baranoglu; Kilinc, Erkan; Töre, Fatma","year":2024,"journal":"Life sciences, 357, 123091","doi":"10.1016/j.lfs.2024.123091","pmid":"39362587","tags":["cgrp","neuropeptides","pain-management"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"TRESK activation by cloxyquin reduced CGRP release, allodynia, and mast cell degranulation in migraine models, with all effects specifically blocked by TRESK inhibitor A2764 and synergistic with sumatriptan ex vivo.","whyItMatters":"CGRP-targeting drugs have revolutionized migraine treatment, but not all patients respond. TRESK channels offer an upstream mechanism to reduce CGRP release, potentially helping patients who don't benefit from current CGRP-blocking therapies.","specificNumbers":"Multiple dose levels of cloxyquin tested; compared against sumatriptan (established migraine drug) and A2764 (TRESK inhibitor) in various combinations.","methodology":"In vivo nitroglycerin-induced migraine model and ex vivo meningeal, trigeminal ganglion, and brainstem preparations in rats, testing TRESK activator cloxyquin, TRESK inhibitor A2764, and sumatriptan alone and in combinations.","limitations":"Animal model results may not fully translate to human migraine; cloxyquin is not a clinically approved drug; synergistic effect seen ex vivo but not in vivo; specific TRESK activators for human use need development; single migraine model tested."},{"rthcId":"RPEP-09399","title":"Liraglutide improves adipose tissue remodeling and mitochondrial dynamics in a visceral obesity model induced by a high-fat diet.","authors":"Touceda, Vanessa; Fontana Estevez, Florencia; Cacciagiú, Leonardo; Finocchietto, Paola; Bustos, Romina; Vidal, Agustina; Berg, Gabriela; Morales, Celina; González, Germán; Miksztowicz, Veronica","year":2024,"journal":"Current research in pharmacology and drug discovery, 6, 100185","doi":"10.1016/j.crphar.2024.100185","pmid":"38846009","tags":["glp-1-receptor-agonists","liraglutide","obesity-and-weight-management"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"Liraglutide restored healthy fat tissue characteristics in obese mice — smaller adipocytes, more blood vessels, higher MMP-9 activity, less fibrosis, and tubular mitochondrial morphology.","whyItMatters":"Understanding how GLP-1 agonists improve visceral fat at the tissue level reveals mechanisms beyond simple weight loss — they actively remodel fat tissue to be healthier, which may explain their metabolic benefits independent of weight change.","specificNumbers":"C57BL/6 mice on high-fat diet; liraglutide treatment groups compared to untreated controls (specific group sizes not detailed in abstract).","methodology":"Controlled animal study with C57BL/6 mice in 4 groups (Control, Control+LGT, HFD, HFD+LGT), with 15 weeks of diet followed by 5 weeks of liraglutide. Epididymal adipose tissue analyzed for histology, vascularity, MMP activity, collagen content, and mitochondrial morphology.","limitations":"Mouse model may not directly translate to human visceral fat biology; only epididymal fat studied (one visceral depot); 5-week treatment is short-term; mitochondrial shape assessed morphologically without functional assays; single liraglutide dose tested."},{"rthcId":"RPEP-09400","title":"Liraglutide exhibits potential anti-tumor effects on the progression of intrahepatic cholangiocarcinoma, in vitro and in vivo.","authors":"Trakoonsenathong, Ronnakrit; Kunprom, Waritta; Aphivatanasiri, Chaiwat; Yueangchantuek, Padcharee; Pimkeeree, Paslada; Sorin, Supannika; Khawkhiaw, Kullanat; Chiu, Ching-Feng; Okada, Seiji; Wongkham, Sopit; Saengboonmee, Charupong","year":2024,"journal":"Scientific reports, 14(1), 13726","doi":"10.1038/s41598-024-64774-2","pmid":"38877189","tags":["glp-1-receptor-agonists","liraglutide","cancer-related-peptides"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Liraglutide suppressed CCA cell migration and reduced xenograft tumor volumes by inhibiting EMT and Akt/STAT3 phosphorylation, despite GLP-1R expression being associated with poorer histological grade.","whyItMatters":"With millions of diabetic patients now on GLP-1 agonists, understanding their effects on cancer is critical. This study suggests liraglutide may have anti-tumor effects on bile duct cancer, a notoriously difficult malignancy with few treatment options.","specificNumbers":"GLP-1R expression significantly associated with poor histological grading (P = 0.027). Two iCCA cell lines tested (KKU-055 and KKU-213A).","methodology":"Immunohistochemistry of GLP-1R in human CCA tissues, in vitro proliferation and migration assays in CCA cell lines (KKU-055, KKU-213A) with exendin-4 and liraglutide, and in vivo xenograft mouse tumor models.","limitations":"Cell line studies may not represent all CCA subtypes; xenograft mice are immunocompromised (may not reflect immune-competent tumor responses); limited sample sizes; only liraglutide and exendin-4 tested; human clinical validation needed; GLP-1R as both risk marker and treatment target creates paradox."},{"rthcId":"RPEP-09401","title":"310-Helix stabilization and screw sense control via stereochemically configured 4-atom hydrocarbon staples.","authors":"Tran, Duc V H; Nguyen, Ha T N; Ahn, Hee-Chul; Kim, Young-Woo","year":2024,"journal":"Bioorganic & medicinal chemistry, 114, 117963","doi":"10.1016/j.bmc.2024.117963","pmid":"39454562","tags":["stapled-peptides","peptide-engineering"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"The Ri,i+3S(4) staple configuration strongly induces right-handed 3₁₀-helices in peptides with natural L-amino acids, with the staple's stereochemistry being critical for both helix stabilization and screw sense control.","whyItMatters":"3₁₀-helices are involved in many important protein interactions but have been difficult to reproduce in synthetic peptides. This technology enables drug designers to create stable 3₁₀-helical peptides that can mimic these interactions, expanding the structural toolbox for peptide therapeutics.","specificNumbers":"4-atom hydrocarbon staples used; circular dichroism spectroscopy confirmed helix stability and screw sense control.","methodology":"Synthesis of stereochemically defined 4-atom hydrocarbon staples via ring-closing metathesis, with circular dichroism spectroscopy to assess 3₁₀-helix formation and screw sense across different configurations and peptide sequences.","limitations":"Demonstrated with model peptides — therapeutic target engagement not tested; CD spectroscopy provides ensemble structure but not atomic-level detail; in vivo stability and cell permeability not assessed; limited to sequences compatible with staple positions."},{"rthcId":"RPEP-09402","title":"Lysine-homologue substitution: Impact on antimicrobial activity and proteolytic stability of cationic stapled heptapeptides.","authors":"Tran, Duc V H; Luong, Huy X; Kim, Do-Hee; Lee, Bong-Jin; Kim, Young-Woo","year":2024,"journal":"Bioorganic & medicinal chemistry, 106, 117735","doi":"10.1016/j.bmc.2024.117735","pmid":"38714021","tags":["antimicrobial-peptides","stapled-peptides","peptide-engineering"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Ornithine substitution for lysine in stapled heptapeptide AMPs enhanced antimicrobial activity and proteolytic stability while maintaining low hemolytic activity.","whyItMatters":"Antimicrobial resistance is a growing global crisis. Developing more potent and stable antimicrobial peptides through simple amino acid substitutions could accelerate the pipeline of new antibiotics.","specificNumbers":"7-amino-acid peptides (heptapeptides) with all-hydrocarbon staples; various lysine homologues tested.","methodology":"Structure-activity study testing lysine-homologue substitutions (ornithine, diaminobutyric acid, diaminopropionic acid) in hydrocarbon-stapled cationic heptapeptides, assessing helicity, antimicrobial MICs, hemolytic activity, and proteolytic stability.","limitations":"In vitro antimicrobial testing only; no in vivo efficacy or toxicity data; limited peptide length (7 residues); mechanism of enhanced activity not fully elucidated; narrow range of bacterial species tested."},{"rthcId":"RPEP-09403","title":"Development and evaluation of C10 and SNAC erodible tablets for gastric delivery of a GIP/GLP1 peptide in monkeys.","authors":"Tran, Huyen; Dogra, Mridula; Huang, Siyuan; Aihara, Eitaro; ElSayed, Mohamed; Aburub, Aktham","year":2024,"journal":"International journal of pharmaceutics, 650, 123680","doi":"10.1016/j.ijpharm.2023.123680","pmid":"38070657","tags":["glp-1-receptor-agonists","gip","drug-delivery-systems","oral-peptide-delivery"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"GIP/GLP-1 dual agonist peptide with higher pepsin stability achieved 4.2% oral bioavailability via SNAC erodible tablets vs 1.2% for semaglutide, a 3.5-fold improvement.","whyItMatters":"Oral peptide delivery could eliminate the need for injections of GLP-1 medications. This study shows that combining improved peptide stability with optimized tablet formulation can dramatically improve oral absorption — potentially leading to more effective oral obesity and diabetes pills.","specificNumbers":"Two permeation enhancers tested (C10 and SNAC); erodible tablet formulation; tested in monkeys for gastric delivery of a GIP/GLP-1 peptide.","methodology":"Development and in vivo evaluation of C10 and SNAC erodible tablets in cynomolgus monkeys, with tissue distribution studies, release kinetics optimization, and comparison to oral semaglutide bioavailability.","limitations":"Monkey data may not directly predict human bioavailability; absolute bioavailability still low (<6%); single-dose study without chronic dosing; only one peptide compared to semaglutide; gastric variability (pH, motility) not fully explored; LY peptide not yet clinically available."},{"rthcId":"RPEP-09404","title":"A structural basis of T cell cross-reactivity to native and spliced self-antigens presented by HLA-DQ8.","authors":"Tran, Mai T; Lim, Jia Jia; Loh, Tiing Jen; Mannering, Stuart I; Rossjohn, Jamie; Reid, Hugh H","year":2024,"journal":"The Journal of biological chemistry, 300(9), 107612","doi":"10.1016/j.jbc.2024.107612","pmid":"39074636","tags":["insulin-and-c-peptide","immune-system-peptides","autoimmune-conditions"],"studyType":"in vitro","evidenceStrength":"moderate","keyFinding":"Five of seven diabetogenic TCRs cross-reacted between proinsulin C-peptide and hybrid insulin peptides containing NPY and IAPP fragments, with structural studies revealing position-specific determinants of cross-reactivity at P2, P7, and P8.","whyItMatters":"Understanding how diabetogenic T cells recognize and cross-react with hybrid peptides reveals fundamental mechanisms of autoimmune diabetes and could guide the development of peptide-based tolerizing therapies or vaccines.","specificNumbers":"Two peptides studied: PI40-54 (proinsulin C-peptide) and HIP PI40-47-IAPP74-80 (hybrid insulin peptide); presented by HLA-DQ8.","methodology":"T cell activation assays with SKW3 cell lines expressing diabetogenic TCRs, crystal structures of TCR-peptide-HLA-DQ8 complexes, and alanine scanning mutagenesis to identify key recognition residues.","limitations":"T cell lines from a small number of patients; SKW3 cell system may not fully represent natural T cell responses; crystal structures represent static snapshots; limited HIP variants tested; HLA-DQ8-restricted findings may not generalize to other HLA types."},{"rthcId":"RPEP-09405","title":"Sa-TTCA: An SVM-based approach for tumor T-cell antigen classification using features extracted from biological sequencing and natural language processing.","authors":"Tran, Thi-Oanh; Le, Nguyen Quoc Khanh","year":2024,"journal":"Computers in biology and medicine, 174, 108408","doi":"10.1016/j.compbiomed.2024.108408","pmid":"38636332","tags":["cancer-related-peptides","immune-system-peptides","biomarkers-and-diagnostics"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Sa-TTCA achieved 87.5% balanced accuracy (training) and 72.0% (independent test) for TTCA prediction by integrating biological descriptors with NLP-derived features from biological language models.","whyItMatters":"Faster, more accurate TTCA prediction accelerates cancer vaccine development by narrowing down which tumor peptides are most likely to trigger immune responses, reducing expensive experimental screening.","specificNumbers":"SVM-based approach combining biological sequence features and NLP features (specific accuracy metrics not detailed in abstract excerpt).","methodology":"Machine learning pipeline using SVM algorithm with features extracted from biological descriptors and biological language models (BLMs), with Chi-square and Pearson correlation feature selection, and SMOTE/Up-sampling/Near-Miss for data balancing.","limitations":"72% independent test accuracy leaves room for improvement; limited training data for TTCAs; model may not capture all relevant structural features; SVM may not scale well to very large datasets; validation against experimental TTCA identification not performed."},{"rthcId":"RPEP-09406","title":"Radiosensitizing Favors Response to Peptide Receptor Radionuclide Therapy in Patients With Highly Proliferative Neuroendocrine Malignancies: Preliminary Evidence From a Clinical Pilot Study.","authors":"Trautwein, Nils Florian; Hinterleitner, Clemens; Kiefer, Lena Sophie; Singer, Stephan; Mattern, Sven; Schwenck, Johannes; Reischl, Gerald; Sipos, Bence; Lauer, Ulrich M; Dittmann, Helmut; Zender, Lars; la Fougère, Christian; Hinterleitner, Martina","year":2024,"journal":"Clinical nuclear medicine, 49(3), 207-214","doi":"10.1097/RLU.0000000000005006","pmid":"38271237","tags":["somatostatin-and-analogues","cancer-related-peptides","radiolabeled-peptides"],"studyType":"cohort","evidenceStrength":"preliminary","keyFinding":"PRRT + CAP/TEM achieved 90% disease control rate (70% partial response) vs 60% (20% PR) for PRRT alone, with 26 vs 12 months median PFS, in high-Ki67 neuroendocrine tumors.","whyItMatters":"Aggressive neuroendocrine tumors have limited treatment options. This study suggests adding oral chemotherapy to PRRT can dramatically improve outcomes for patients with higher-proliferation tumors without increasing side effects.","specificNumbers":"20 patients with histologically confirmed gastroenteropancreatic neuroendocrine tumors with higher proliferation rates and somatostatin receptor positivity.","methodology":"Retrospective cohort study of 20 patients with GEP-NET (Ki67 15-55%), comparing PRRT alone (n=10) to PRRT + capecitabine/temozolomide (n=10) for at least 2 cycles, with RECIST response, PFS, DSS, metabolic tumor volume, and chromogranin A endpoints.","limitations":"Small retrospective study (20 patients); not randomized; potential selection bias; short follow-up for some patients; Ki67 15-55% represents a heterogeneous group; single-center experience."},{"rthcId":"RPEP-09407","title":"Potential kidney protective effects of glucagon-like peptide-1 receptor agonists.","authors":"Trevella, Philippa; Ekinci, Elif I; MacIsaac, Richard J","year":2024,"journal":"Nephrology (Carlton, Vic.), 29(8), 457-469","doi":"10.1111/nep.14336","pmid":"39030739","tags":["glp-1-receptor-agonists","kidney-health"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"The FLOW trial demonstrated a 24% reduction in a composite kidney/cardiovascular endpoint with semaglutide in T2DM patients with CKD, validating GLP-1 RA kidney protection.","whyItMatters":"Diabetic kidney disease is a leading cause of kidney failure worldwide. GLP-1 agonists could join SGLT2 inhibitors as another class of kidney-protective diabetes medications, giving clinicians more options to slow kidney decline.","specificNumbers":"Review covered evidence on albuminuria reduction, eGFR preservation, and cardiovascular risk mitigation across multiple studies.","methodology":"Narrative review synthesizing clinical trial evidence, mechanistic studies, and preliminary FLOW trial results on GLP-1 RA kidney protective effects in type 2 diabetes with chronic kidney disease.","limitations":"Review written before full FLOW trial data publication; mechanistic pathways largely from preclinical data; unclear whether kidney benefits are independent of glucose and weight effects; not all GLP-1 RAs may have equivalent kidney protection; dose adjustment needed in severe CKD."},{"rthcId":"RPEP-09408","title":"Efficacy of eptinezumab in non-responders to subcutaneous monoclonal antibodies against CGRP and the CGRP receptor: A retrospective cohort study.","authors":"Triller, Paul; Blessing, Virginia N; Overeem, Lucas H; Fitzek, Mira P; Hong, Ja Bin; Lange, Kristin S; Reuter, Uwe; Raffaelli, Bianca","year":2024,"journal":"Cephalalgia : an international journal of headache, 44(10), 3331024241288875","doi":"10.1177/03331024241288875","pmid":"39469839","tags":["cgrp","pain-management"],"studyType":"cohort","evidenceStrength":"preliminary","keyFinding":"29.7% of patients who failed multiple subcutaneous CGRP antibodies achieved ≥30% reduction in monthly migraine days with eptinezumab by week 24, with 52.4% showing clinically meaningful MIDAS improvement.","whyItMatters":"Treatment-refractory migraine patients have exhausted most options. This study suggests that the different delivery mechanism (IV vs subcutaneous) and pharmacology of eptinezumab may reach patients who don't respond to other CGRP antibodies.","specificNumbers":"Patients had previously failed erenumab plus at least one other subcutaneous CGRP mAb (fremanezumab and/or galcanezumab) before switching to eptinezumab.","methodology":"Retrospective cohort study of 41 migraine patients who failed erenumab plus at least one other CGRP(-R) mAb, treated with eptinezumab 100 mg IV (most escalated to 300 mg), with headache diary and patient-reported outcomes at baseline, weeks 12 and 24.","limitations":"Retrospective design without placebo control; small sample (41 patients); regression to the mean possible; patients may have improved regardless of treatment change; 24-week follow-up may be insufficient; no formal statistical significance achieved for primary outcomes."},{"rthcId":"RPEP-09409","title":"GLP-1 receptor agonists and weight loss in schizophrenia - past, present, and future.","authors":"Trott, Mike; Arnautovska, Urska; Siskind, Dan","year":2024,"journal":"Current opinion in psychiatry, 37(5), 363-369","doi":"10.1097/YCO.0000000000000952","pmid":"38847529","tags":["glp-1-receptor-agonists","obesity-and-weight-management","mental-health-peptides"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"GLP-1 RAs decrease weight in schizophrenia patients, but effect sizes are mostly smaller than in the general population. Six trials completed, three ongoing, with future directions including dual agonists and early intervention.","whyItMatters":"Antipsychotic-induced weight gain is a leading cause of medication non-adherence and reduced lifespan in schizophrenia. Effective weight management could improve both physical health and psychiatric outcomes in this vulnerable population.","specificNumbers":"3-5 times higher prevalence of diabetes and obesity in schizophrenia patients; 20-year reduced lifespan compared to general population.","methodology":"Narrative review of all completed and in-progress clinical trials of GLP-1 receptor agonists for weight management in people with schizophrenia.","limitations":"Narrative review without meta-analysis; most completed trials are small; limited head-to-head comparisons; antipsychotic medication variability across studies; short trial durations; unclear whether weight benefits improve psychiatric outcomes or medication adherence."},{"rthcId":"RPEP-09410","title":"Advances in obesity pharmacotherapy; learning from metabolic surgery and beyond.","authors":"Tsilingiris, Dimitrios; Kokkinos, Alexander","year":2024,"journal":"Metabolism: clinical and experimental, 151, 155741","doi":"10.1016/j.metabol.2023.155741","pmid":"37995806","tags":["glp-1-receptor-agonists","gip","glucagon-and-related","obesity-and-weight-management"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Dual and triple gut hormone polyagonists are approaching bariatric surgery-level weight loss, potentially enabling pharmacological replication of surgical metabolic benefits through targeted peptide hormone therapy.","whyItMatters":"If peptide medications can replicate bariatric surgery outcomes, it could dramatically expand access to effective obesity treatment — surgery is limited by capacity, cost, and patient willingness, while medications can reach far more people.","specificNumbers":"Review covers GLP-1, GIP, glucagon, and other gut peptide targets; some drugs approaching surgery-level weight loss results.","methodology":"Narrative review synthesizing evidence on bariatric surgery mechanisms, GLP-1 RA clinical data, and emerging dual/triple polyagonist results to evaluate the feasibility of a 'medical bypass' concept.","limitations":"Review article with no new primary data; long-term durability of pharmacological weight loss unclear; surgical benefits on mortality not yet matched by medications; cost and access barriers may shift rather than disappear; weight regain after medication discontinuation remains a concern."},{"rthcId":"RPEP-09411","title":"Somatostatin Receptor Imaging in the Diagnosis and Management of Parathyroid Neuroendocrine Neoplasia.","authors":"Tsoy, Uliana; Pogosian, Karina; Ryzhkova, Daria; Yudina, Olga; Yakovenko, Ksenia; Ryazanov, Pavel; Matsueva, Irina; Sokolnikova, Polina; Salov, Maksim; Karonova, Tatiana; Grineva, Elena","year":2024,"journal":"Diagnostics (Basel, Switzerland), 14(23)","doi":"10.3390/diagnostics14232718","pmid":"39682626","tags":["somatostatin-and-analogues","radiolabeled-peptides","biomarkers-and-diagnostics"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"[68Ga]-DOTA-peptide PET/CT detected parathyroid adenomas with high uptake, likely mediated by endothelial somatostatin receptor expression, and somatostatin analog therapy reduced serum calcium in hyperparathyroid patients.","whyItMatters":"This study opens two clinical doors: using somatostatin receptor imaging as a diagnostic tool for parathyroid tumors (especially as incidental findings during cancer workups), and potentially using somatostatin analogs as medical therapy for hyperparathyroidism when surgery isn't an option.","specificNumbers":"50 patients with primary hyperparathyroidism; all had histologically confirmed parathyroid adenomas; [68Ga]-DOTA-peptide PET/CT imaging used.","methodology":"Prospective cohort study of 50 patients with primary hyperparathyroidism and histologically confirmed parathyroid adenomas. PET/CT imaging performed in 16 patients, immunohistochemistry for SST2/SST5 in 48 patients, and somatostatin analog therapy evaluated in 5 patients.","limitations":"Small sample for therapeutic assessment (only 5 patients on somatostatin analogs). No head-to-head comparison with standard parathyroid imaging (sestamibi, ultrasound). SST2 was negative on tumor cell membranes in all cases, so the uptake mechanism differs from typical neuroendocrine tumors. iPTH levels did not decrease despite calcium reduction."},{"rthcId":"RPEP-09412","title":"Sexual dimorphism in prokinetic effects of a ghrelin agonist acting through the lumbosacral defecation center in rats.","authors":"Tsukamoto, Shumpei; Sawamura, Tomoya; Yuki, Natsufu; Horii, Kazuhiro; Horii, Yuuki; Homma, Takeshi; Saito, Shouichiro; Shiina, Takahiko; Shimizu, Yasutake","year":2024,"journal":"The journal of physiological sciences : JPS, 74(1), 54","doi":"10.1186/s12576-024-00949-w","pmid":"39578725","tags":["ghrelin","gut-health-peptides"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"The ghrelin agonist RQ-00538053 enhanced colorectal motility in female rats but required ~10× higher doses than in males, correlating with lower ghrelin receptor expression in the female lumbosacral spinal cord.","whyItMatters":"Constipation disproportionately affects women. If ghrelin-based drugs for gut motility require sex-specific dosing, clinical trials and eventual prescribing must account for this biological difference — otherwise, women may be systematically underdosed.","specificNumbers":"Approximately 10-fold higher doses needed in female vs. male rats for similar colorectal motility responses; tested via both intravenous and intrathecal routes.","methodology":"Pharmacological study comparing intravenous and intrathecal (lumbosacral spinal cord) administration of ghrelin agonist RQ-00538053 in male and female Sprague-Dawley rats, with RT-qPCR analysis of ghrelin receptor expression.","limitations":"Animal study in rats — sex differences in ghrelin receptor expression may differ in humans. Only one ghrelin agonist tested. Sample size not specified in abstract. The mechanism is partially explained (receptor expression) but other factors (hormonal, metabolic) may contribute."},{"rthcId":"RPEP-09413","title":"Effect of tirzepatide on glycaemic control and weight loss compared with other glucagon-like peptide-1 receptor agonists in Japanese patients with type 2 diabetes mellitus.","authors":"Tsukamoto, Shunichiro; Tanaka, Shohei; Yamada, Takayuki; Uneda, Kazushi; Azushima, Kengo; Kinguchi, Sho; Wakui, Hiromichi; Tamura, Kouichi","year":2024,"journal":"Diabetes, obesity & metabolism, 26(1), 262-274","doi":"10.1111/dom.15312","pmid":"37828829","tags":["glp-1-receptor-agonists","gip","tirzepatide","diabetes-and-blood-sugar"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Tirzepatide demonstrated superior HbA1c reduction and body weight loss compared to GLP-1 receptor agonists alone in a network meta-analysis of 18 RCTs in Japanese type 2 diabetes patients.","whyItMatters":"Japanese patients have distinct metabolic characteristics (lower BMI at diabetes onset, different insulin secretion patterns) that may influence drug response. This Japan-specific evidence supports tirzepatide's dual mechanism advantage in this population.","specificNumbers":"Network meta-analysis of multiple RCTs; compared tirzepatide (GIP/GLP-1RA) to GLP-1RAs on HbA1c and body weight outcomes in Japanese T2D patients.","methodology":"Systematic review and network meta-analysis of 18 randomized controlled trials from PubMed, MEDLINE, EMBASE, and Cochrane Library (through July 2023), comparing GLP-1RAs and GIP/GLP-1RAs in Japanese T2D patients.","limitations":"Network meta-analysis uses indirect comparisons rather than direct head-to-head trials. Heterogeneous trial designs and follow-up periods. Focused exclusively on Japanese patients, limiting generalizability. Long-term safety comparison not addressed."},{"rthcId":"RPEP-09414","title":"The Tirzepatide Drop: Beware of Slimmer's Paralysis.","authors":"Tucker, John M; Ritchie, Jordan","year":2024,"journal":"Journal of investigative medicine high impact case reports, 12, 23247096241264635","doi":"10.1177/23247096241264635","pmid":"39051436","tags":["tirzepatide","glp-1-receptor-agonists","gip","safety-and-side-effects"],"studyType":"case series","evidenceStrength":"preliminary","keyFinding":"Two patients on tirzepatide developed bilateral peroneal nerve neuropathy (foot drop) within 6-8 months, caused by rapid weight loss-related nerve compression known as slimmer's paralysis.","whyItMatters":"As tirzepatide and similar drugs achieve unprecedented weight loss speeds, rare complications like slimmer's paralysis may become more common. Early recognition and monitoring can prevent permanent nerve damage.","specificNumbers":"2 patients; bilateral foot drop in both cases; developed within 6-8 months of tirzepatide initiation.","methodology":"Case series of 2 patients who developed bilateral foot drop after tirzepatide-induced rapid weight loss. Clinical presentation, timeline, and outcomes documented.","limitations":"Only 2 cases reported — cannot determine incidence or prevalence. No controlled comparison group. Association with tirzepatide is temporal, not definitively causal. Other risk factors for peroneal neuropathy not fully explored."},{"rthcId":"RPEP-09415","title":"Cutaneous Neuroendocrine Metastases of Visceral Origin Responsive to Surgical Resection and Targeted Radionuclide Therapy.","authors":"Tung-Hahn, Eleanor; El-Haddad, Ghassan; Strosberg, Jonathan","year":2024,"journal":"Case reports in dermatological medicine, 2024, 8873822","doi":"10.1155/2024/8873822","pmid":"38352716","tags":["somatostatin-and-analogues","radiolabeled-peptides","cancer-related-peptides"],"studyType":"case series","evidenceStrength":"preliminary","keyFinding":"Cutaneous neuroendocrine metastases from visceral origins, though rare, can be managed with surgical resection and peptide receptor radionuclide therapy (PRRT) targeting somatostatin receptors.","whyItMatters":"Skin lesions from neuroendocrine tumors can be misdiagnosed, delaying treatment. Recognizing these as metastatic NETs opens the door to targeted peptide therapies (PRRT) that can control even distant disease.","specificNumbers":"Single patient case; combination of surgical resection and targeted radionuclide therapy.","methodology":"Case series documenting cutaneous neuroendocrine metastases of visceral origin, their histologic characterization, and treatment response to surgery and PRRT.","limitations":"Case series with limited patient numbers — cannot establish response rates or survival benefit. Selection bias toward patients with somatostatin receptor-positive tumors. Generalizability limited to well-differentiated NETs."},{"rthcId":"RPEP-09416","title":"Effects of Once-Weekly Semaglutide on Kidney Disease Outcomes by KDIGO Risk Category in the SUSTAIN 6 Trial.","authors":"Tuttle, Katherine R; Bain, Stephen C; Bosch-Traberg, Heidrun; Khunti, Kamlesh; Rasmussen, Søren; Sokareva, Ekaterina; Cherney, David Z","year":2024,"journal":"Kidney international reports, 9(7), 2006-2015","doi":"10.1016/j.ekir.2024.04.028","pmid":"39081763","tags":["glp-1-receptor-agonists","semaglutide","kidney-health"],"studyType":"RCT","evidenceStrength":"strong","keyFinding":"Once-weekly semaglutide improved kidney disease outcomes consistently across all KDIGO risk categories in SUSTAIN 6 participants with T2D and cardiovascular disease or high CV risk.","whyItMatters":"Kidney disease is a leading complication of diabetes. This analysis provides evidence that semaglutide's kidney benefits extend across the full spectrum of kidney disease severity — supporting its use even in patients who already have significant kidney impairment.","specificNumbers":"Post hoc analysis of SUSTAIN 6 trial; kidney outcomes assessed across all KDIGO risk categories; compared once-weekly semaglutide vs. placebo.","methodology":"Post hoc analysis of the SUSTAIN 6 randomized controlled trial, stratifying participants by KDIGO risk category to assess semaglutide's effects on kidney disease outcomes and KDIGO risk category transitions vs. placebo.","limitations":"Post hoc analysis — not the primary trial endpoint. SUSTAIN 6 was designed for cardiovascular outcomes, not kidney endpoints. Subgroup analyses may lack power for individual KDIGO categories. Median follow-up of ~2 years may miss long-term kidney effects."},{"rthcId":"RPEP-09417","title":"A novel chitosan-peptide system for cartilage tissue engineering with adipose-derived stromal cells.","authors":"Tymińska, Agata; Karska, Natalia; Skoniecka, Aneta; Zawrzykraj, Małgorzata; Banach-Kopeć, Adrianna; Mania, Szymon; Zieliński, Jacek; Kondej, Karolina; Gurzawska-Comis, Katarzyna; Skowron, Piotr M; Tylingo, Robert; Rodziewicz-Motowidło, Sylwia; Pikuła, Michał","year":2024,"journal":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 181, 117683","doi":"10.1016/j.biopha.2024.117683","pmid":"39561590","tags":["peptide-engineering","bone-and-joint-health","drug-delivery-systems"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"A chitosan-peptide composite scaffold promoted chondrogenic differentiation of adipose-derived stromal cells in vitro, demonstrating potential for cartilage tissue engineering applications.","whyItMatters":"Cartilage injuries affect millions and have limited treatment options. Combining bioactive peptides with natural polymer scaffolds could create practical, scalable solutions for cartilage regeneration — potentially replacing the need for donor cartilage.","specificNumbers":"Chitosan-peptide composite scaffold; adipose-derived stromal cells as cell source (specific metrics not detailed in abstract excerpt).","methodology":"In vitro tissue engineering study. Chitosan scaffolds were functionalized with chondrogenic peptides and seeded with adipose-derived stromal cells. Cartilage differentiation markers were assessed.","limitations":"In vitro study only — no animal or human testing. Long-term mechanical properties of regenerated cartilage not assessed. Translation from lab-grown cartilage to functional joint repair faces major challenges. Specific peptide sequence and optimization details may be limited."},{"rthcId":"RPEP-09418","title":"Pathological complete response of initially unresectable multiple liver metastases achieved using combined peptide receptor radionuclide therapy and somatostatin analogs following pancreatic neuroendocrine tumor resection: a case report.","authors":"Umino, Ryosuke; Nara, Satoshi; Kobayashi, Noritoshi; Mizui, Takahiro; Takamoto, Takeshi; Ban, Daisuke; Esaki, Minoru; Hiraoka, Nobuyoshi; Shimada, Kazuaki","year":2024,"journal":"Surgical case reports, 10(1), 40","doi":"10.1186/s40792-024-01839-4","pmid":"38353868","tags":["somatostatin-and-analogues","radiolabeled-peptides","cancer-related-peptides"],"studyType":"case series","evidenceStrength":"preliminary","keyFinding":"PRRT combined with somatostatin analogs achieved pathological complete response of initially unresectable multiple liver metastases from a pancreatic neuroendocrine tumor, enabling curative surgical resection.","whyItMatters":"Complete pathological responses to PRRT are rarely documented. This case demonstrates that peptide-targeted radionuclide therapy can potentially convert unresectable metastatic disease into a surgically curable condition — representing the best possible outcome of targeted peptide therapy.","specificNumbers":"1 patient; multiple initially unresectable liver metastases; complete pathological response after PRRT + somatostatin analogs.","methodology":"Single case report of a 52-year-old male with pancreatic NET and initially unresectable liver metastases treated with PRRT and SSAs, followed by conversion surgery with pathological assessment.","limitations":"Single case report — cannot generalize outcomes. Pathological complete responses to PRRT are very rare. Patient selection factors (tumor grade, receptor expression, metastatic burden) heavily influence outcomes. No long-term recurrence data provided."},{"rthcId":"RPEP-09419","title":"Model-based simulation of glycaemic effect and body weight loss when switching from semaglutide or dulaglutide to once weekly tirzepatide.","authors":"Urva, Shweta; Levine, Joshua A; Schneck, Karen; Tang, Cheng Cai","year":2024,"journal":"Current medical research and opinion, 40(4), 567-574","doi":"10.1080/03007995.2024.2322072","pmid":"38407177","tags":["glp-1-receptor-agonists","gip","tirzepatide","semaglutide","diabetes-and-blood-sugar"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Model-based simulations predict additional HbA1c and body weight reductions when switching from semaglutide or dulaglutide to tirzepatide, with magnitude depending on prior therapy and dose.","whyItMatters":"Many patients on GLP-1 RAs may benefit from switching to tirzepatide, but clinicians lack data on expected outcomes during the transition. These models provide practical guidance for a common clinical decision — when and what to expect when upgrading therapy.","specificNumbers":"Models built from SUSTAIN 1-10, AWARD-11, and SURPASS 1-5 trial data; simulated switching from once-weekly semaglutide or dulaglutide to tirzepatide.","methodology":"Pharmacometric modeling using validated models developed from SUSTAIN 1-10 (semaglutide), AWARD-11 (dulaglutide), and SURPASS 1-5 (tirzepatide) phase 3 trial data. Simulated switching scenarios with efficacy time-course projections.","limitations":"Model-based simulation, not real clinical trial data. Predictions depend on model assumptions and may not capture all real-world factors (adherence, comorbidities, concomitant medications). No safety outcome modeling. Models derived from trial populations that may not represent all patients."},{"rthcId":"RPEP-09420","title":"TRPV1-positive sensory nerves and neuropeptides are involved in epidermal barrier repair after tape stripping in mice.","authors":"Usui, Kenji; Nakashima, Chisa; Takahashi, Sonoko; Okada, Takaharu; Ishida, Yoshihiro; Nakajima, Saeko; Kitoh, Akihiko; Nomura, Takashi; Dainichi, Teruki; Honda, Tetsuya; Katsumoto, Rumi; Konishi, Noriko; Matsushita, Mutsuyoshi; Otsuka, Atsushi; Kabashima, Kenji","year":2024,"journal":"The Journal of allergy and clinical immunology, 153(3), 868-873.e4","doi":"10.1016/j.jaci.2023.11.024","pmid":"38040043","tags":["neuropeptides","skin-and-wound-healing"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"TRPV1-positive sensory nerves and neuropeptides (substance P and CGRP) are required for epidermal barrier repair after tape stripping, with involvement of filaggrin biosynthesis in the restoration process.","whyItMatters":"Understanding how nerves help repair skin could transform treatment of barrier-deficient skin conditions like eczema, psoriasis, and dry skin. If neuropeptides like substance P and CGRP drive barrier restoration, they could become therapeutic targets for skin repair.","specificNumbers":"TRPV1-positive sensory nerves identified as participants in barrier repair; filaggrin (encoded by Flg gene) production involved in the process.","methodology":"Animal study in mice using tape stripping to disrupt the epidermal barrier. Assessed TRPV1-positive sensory nerve involvement, neuropeptide (substance P, CGRP) contribution, and filaggrin expression during barrier repair.","limitations":"Mouse study — skin structure and innervation differ between mice and humans. Tape stripping is a simplified model that doesn't fully replicate clinical barrier damage. Specific neuropeptide receptor pathways not fully dissected. Quantitative contribution of each neuropeptide not determined."},{"rthcId":"RPEP-09421","title":"The physiology and pharmacology of oxytocin in labor and in the peripartum period.","authors":"Uvnäs-Moberg, Kerstin","year":2024,"journal":"American journal of obstetrics and gynecology, 230(3S), S740-S758","doi":"10.1016/j.ajog.2023.04.011","pmid":"38462255","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09422","title":"Semaglutide treatment for children with obesity: an observational study.","authors":"van Boxel, Elizabeth-Jane; Rahman, Saqib; Lai, Karen; Boulos, Nabil; Davis, Nikki","year":2024,"journal":"Archives of disease in childhood, 109(10), 822-825","doi":"10.1136/archdischild-2023-326687","pmid":"38471743","tags":["glp-1-receptor-agonists","semaglutide","obesity-and-weight-management"],"studyType":"cohort","evidenceStrength":"preliminary","keyFinding":"Once-weekly semaglutide 1 mg in children aged 10-18 with comorbid obesity produced 6.4% total weight loss at 6 months and 8.9% at 12 months in a real-world UK pediatric clinic.","whyItMatters":"Childhood obesity with comorbidities is a growing crisis with limited pharmacological options. This real-world evidence supports semaglutide's safety and efficacy in children — complementing clinical trial data with practical clinical experience.","specificNumbers":"50 children; ages 10-18; BMI SD score >2; all with weight-related comorbidities including insulin resistance; minimum 6 months treatment.","methodology":"Retrospective observational study of 50 children from a tertiary paediatric multidisciplinary weight management clinic in a UK hospital, treated with semaglutide for at least 6 months.","limitations":"Retrospective observational study without a control group. Only 50 patients, with 12-month data available for only 14. Single center in the UK. Maximum dose was 1 mg (lower than the 2.4 mg used for weight management in adults). No long-term follow-up beyond 12 months."},{"rthcId":"RPEP-09423","title":"GLP-1R agonist therapy and vaccine response: Neglected implications.","authors":"van Niekerk, Gustav; Coelmont, Lotte; Alpizar, Yeranddy A; Kelchtermans, Lara; Broeckhoven, Elias; Dallmeier, Kai","year":2024,"journal":"Cytokine & growth factor reviews, 78, 14-24","doi":"10.1016/j.cytogfr.2024.07.006","pmid":"39025754","tags":["glp-1-receptor-agonists","semaglutide","immune-system-peptides","safety-and-side-effects"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"GLP-1 receptor agonists may reduce vaccine immunogenicity through direct effects on immune cells and creation of a tolerogenic environment, representing a neglected pharmacological concern.","whyItMatters":"With tens of millions of people now on GLP-1 drugs, even a modest reduction in vaccine effectiveness could have significant public health consequences — particularly for seasonal flu, COVID, and other routine immunizations.","specificNumbers":"Natural GLP-1 half-life <5 minutes in picomolar range; semaglutide half-life several days at supraphysiological doses.","methodology":"Narrative review examining evidence for GLP-1R signaling effects on immune function and potential implications for vaccine efficacy.","limitations":"Review based on indirect evidence and mechanistic reasoning — no clinical studies directly measuring vaccine responses in GLP-1RA users. Theoretical concerns may not translate to clinically meaningful reductions in vaccine efficacy. Does not quantify the magnitude of potential immune effects."},{"rthcId":"RPEP-09424","title":"Perioperative Considerations for Patients on GLP1 Agonists.","authors":"VanderWielen, Beth A; Brian Beam, William","year":2024,"journal":"Advances in anesthesia, 42(1), 1-26","doi":"10.1016/j.aan.2024.07.002","pmid":"39443044","tags":["glp-1-receptor-agonists","safety-and-side-effects"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"GLP-1 receptor agonists delay gastric emptying across multiple tissue sites, creating clinically significant aspiration risk during anesthesia that requires modified perioperative fasting and medication management protocols.","whyItMatters":"With the explosion of GLP-1RA prescribing, anesthesia providers are seeing these patients daily. Delayed gastric emptying can turn a routine surgery into a dangerous aspiration event if standard fasting protocols are assumed to be sufficient.","specificNumbers":"GLP-1RAs shown to provide reliable weight loss and improved glycemic control; improve cardiovascular outcomes in high-risk populations; cause delayed gastric emptying.","methodology":"Clinical review addressing perioperative implications of GLP-1 receptor agonists for anesthesia professionals, covering pharmacology, organ effects, and clinical management recommendations.","limitations":"Review article — does not provide new clinical data. Specific timing recommendations for medication withholding may evolve as evidence accumulates. Individual patient factors (dose, duration of therapy, specific agent) affect gastric emptying differently."},{"rthcId":"RPEP-09425","title":"Semaglutide in patients with kidney failure and obesity undergoing dialysis and wishing to be transplanted: A prospective, observational, open-label study.","authors":"Vanek, Lenka; Kurnikowski, Amelie; Krenn, Simon; Mussnig, Sebastian; Hecking, Manfred","year":2024,"journal":"Diabetes, obesity & metabolism, 26(12), 5931-5941","doi":"10.1111/dom.15967","pmid":"39375862","tags":["glp-1-receptor-agonists","semaglutide","kidney-health","obesity-and-weight-management"],"studyType":"cohort","evidenceStrength":"preliminary","keyFinding":"Semaglutide achieved significant weight and BMI reduction in obese dialysis patients (mean 4.6 kg in 12 weeks), with an acceptable safety profile, and three patients were able to reconsider transplant listing.","whyItMatters":"Kidney transplantation dramatically improves survival and quality of life compared to dialysis, but obesity barriers prevent many patients from even being listed. Semaglutide could serve as a bridge therapy, helping patients lose enough weight to access transplantation.","specificNumbers":"13 patients; 12-week prospective open-label trial; all on dialysis with BMI above transplant thresholds.","methodology":"Prospective, 12-week, open-label, observational study of 13 patients with BMI ≥30 undergoing dialysis, treated with weekly subcutaneous semaglutide titrated from 0.25 mg to 1 mg. Primary endpoint: weight/BMI change by repeated measures ANOVA.","limitations":"Very small sample (n=13). Open-label without control group. Short 12-week treatment period. Two deaths (unrelated) in a high-risk population. Long-term safety in dialysis not established. No pharmacokinetic data specific to dialysis clearance."},{"rthcId":"RPEP-09426","title":"Screening and computational characterization of novel antimicrobial cathelicidins from amphibian transcriptomic data.","authors":"Varela-Rodríguez, H; Guzman-Pando, A; Camarillo-Cisneros, J","year":2024,"journal":"Computational biology and chemistry, 113, 108276","doi":"10.1016/j.compbiolchem.2024.108276","pmid":"39546857","tags":["antimicrobial-peptides","cathelicidins","peptide-engineering"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"210 novel cathelicidin sequences identified from amphibian transcriptomes using computational screening, with predicted antimicrobial activity and low hemolytic toxicity, significantly expanding the known cathelicidin repertoire.","whyItMatters":"Antibiotic resistance is a global crisis. Antimicrobial peptides from amphibians represent a vast, largely untapped resource. This study shows that computational methods can dramatically accelerate the discovery of new AMP candidates from existing genetic data.","specificNumbers":"Multiple novel cathelicidins identified from amphibian transcriptomic data (specific numbers not detailed in abstract excerpt).","methodology":"Computational pipeline using HMMER and BLAST to screen amphibian transcriptomic databases for cathelicidin domains. Sequences validated with SignalP and InterProScan. Phylogenetic analysis with IQ-TREE. Antimicrobial and hemolytic activity predicted with AMPlify, ampir, AmpGram, and HemoPI. 3D modeling with AlphaFold2.","limitations":"Entirely computational — no experimental validation of antimicrobial activity. Predicted antimicrobial and hemolytic properties may not reflect actual biological activity. Production and stability of these peptides as therapeutics not assessed. Some amphibian transcriptomes may be incomplete or poorly annotated."},{"rthcId":"RPEP-09427","title":"Comparison of Treatment Patterns in Patients with Migraine Initiating Calcitonin Gene-Related Peptide Monoclonal Antibodies: A Retrospective Real-World US Study.","authors":"Varnado, Oralee J; Brady, Brenna L; Zagar, Anthony J; Robles, Yvonne P; Hoyt, Margaret","year":2024,"journal":"Patient preference and adherence, 18, 69-88","doi":"10.2147/PPA.S437396","pmid":"38223442","tags":["cgrp","pain-management"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Galcanezumab initiators showed higher treatment persistence (248 days vs 237-242 days), lower discontinuation rates, and slightly better adherence compared to fremanezumab and erenumab initiators at 12 months.","whyItMatters":"Treatment adherence is critical for migraine prevention — patients who stay on therapy longer get better results. Understanding which CGRP antibody patients are most likely to stick with helps guide prescribing decisions and patient counseling.","specificNumbers":"Three CGRP mAbs compared: galcanezumab, fremanezumab, and erenumab; US claims database; continuous enrollment required.","methodology":"Retrospective claims-based study using Merative MarketScan Commercial and Medicare databases (May 2017 - March 2021). Propensity-score matched cohorts: 2,674 galcanezumab-fremanezumab pairs and 3,503 galcanezumab-erenumab pairs. Outcomes: PDC, MPR, persistence, discontinuation, switching.","limitations":"Claims-based study — cannot determine reasons for discontinuation or switching. Propensity-score matching reduces but doesn't eliminate confounding. Cannot assess clinical outcomes (headache frequency, severity). Data period (2017-2021) may not reflect current prescribing patterns. Funded by Eli Lilly (manufacturer of galcanezumab)."},{"rthcId":"RPEP-09428","title":"Patient-reported outcomes related to migraine burden among patients treated with standard-of-care preventive medications or calcitonin gene-related monoclonal antibodies: a United States and Europe cross-sectional survey.","authors":"Varnado, Oralee J; Jackson, James; Scharf, Lucas; Kim, Gilwan; Cotton, Sarah","year":2024,"journal":"Current medical research and opinion, 40(12), 2179-2190","doi":"10.1080/03007995.2024.2427884","pmid":"39523857","tags":["cgrp","pain-management"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Patients with 3+ lines of prior preventive therapy who received CGRP mAbs (including galcanezumab) showed enhanced health-related quality of life compared to standard-of-care preventives in European and overall populations.","whyItMatters":"Patients who've failed multiple migraine preventives represent the most burdened group. Demonstrating real-world quality-of-life improvements with CGRP antibodies in this population validates their role as a meaningful therapeutic advance, not just another option.","specificNumbers":"Survey data from US and Europe; compared CGRP mAbs vs. standard preventive medications on quality of life, disability, and work productivity measures.","methodology":"Cross-sectional survey using the Adelphi Migraine Disease Specific Programme (May 2022 - June 2023). 557 physicians completed record forms for 6,723 patients across the US and Europe. 4,036 patients with preventive treatment history analyzed using t-tests, Fisher's exact test, and Mann-Whitney U test.","limitations":"Cross-sectional design — cannot establish causation. Potential physician selection bias in patient enrollment. Quality-of-life difference not significant in US subgroup. Industry-funded (Eli Lilly). Patient self-report may be influenced by expectations of newer therapy."},{"rthcId":"RPEP-09429","title":"Existing and emerging GLP-1 receptor agonist therapy: Ramifications for diabetic retinopathy screening.","authors":"Varughese, George Iype; Jacob, Sarita","year":2024,"journal":"The journal of the Royal College of Physicians of Edinburgh, 54(2), 170-173","doi":"10.1177/14782715241244843","pmid":"38578067","tags":["glp-1-receptor-agonists","diabetes-and-blood-sugar","safety-and-side-effects"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"GLP-1 receptor agonists can cause transient early worsening of diabetic retinopathy through rapid glycemic improvement, and the 2024 drug shortage/re-initiation cycle creates additional retinal screening urgency.","whyItMatters":"Millions of diabetic patients use GLP-1 drugs, and many have some degree of retinopathy. The combination of drug shortages and re-initiation creates a perfect storm for eye complications unless clinicians proactively screen for retinopathy status before resuming therapy.","specificNumbers":"GLP-1RAs cause rapid glucose improvement linked to transient worsening of pre-existing diabetic retinopathy (specific rates not detailed).","methodology":"Clinical review examining the relationship between GLP-1 RA therapy, rapid glycemic improvement, and diabetic retinopathy worsening, with specific attention to supply shortage implications.","limitations":"Review article — no new clinical data. The magnitude and duration of DR worsening with GLP-1RAs varies. Not all patients with DR are affected. Supply shortage duration and impact may vary by region and specific agent."},{"rthcId":"RPEP-09430","title":"Management of Type 2 Diabetes Mellitus With Noninsulin Pharmacotherapy.","authors":"Vaughan, Elizabeth M; Santiago-Delgado, Zuleica M","year":2024,"journal":"American family physician, 109(4), 333-342","doi":null,"pmid":"38648832","tags":["glp-1-receptor-agonists","diabetes-and-blood-sugar"],"studyType":"review","evidenceStrength":"strong","keyFinding":"GLP-1 receptor agonists and SGLT2 inhibitors provide cardiovascular, renal, and weight benefits beyond glucose control, establishing them as preferred agents for type 2 diabetes management in patients with cardiorenal risk.","whyItMatters":"Type 2 diabetes treatment has evolved from simply lowering blood sugar to protecting hearts, kidneys, and managing weight. GLP-1 agonists are at the center of this transformation, but cost and access barriers mean many patients still can't benefit from these advances.","specificNumbers":"Metformin is first-line; sulfonylureas and thiazolidinediones are low-cost alternatives; GLP-1RAs and SGLT2i offer additional cardiovascular and renal benefits.","methodology":"Comprehensive clinical review of non-insulin pharmacotherapy for type 2 diabetes mellitus, covering mechanisms, efficacy, safety, and access across all available drug classes.","limitations":"Review article — no new data. Does not address combination therapy strategies in detail. Access and cost issues acknowledged but not solved. Some drug class comparisons lack head-to-head trial data. Rapidly evolving field — dual agonists (tirzepatide) only briefly covered."},{"rthcId":"RPEP-09431","title":"Improvement of osteogenesis and antibacterial properties of a bioactive glass/gelatin-based scaffold using zoledronic acid and CM11 peptide.","authors":"Vazifehdoust, Soheil; Shalizar-Jalali, Ali; Nourani, Mohammad Reza; Moosazadeh Moghaddam, Mehrdad; Yazdanian, Mohsen","year":2024,"journal":"Veterinary research forum : an international quarterly journal, 15(9), 487-498","doi":"10.30466/vrf.2024.2020333.4136","pmid":"39564474","tags":["antimicrobial-peptides","bone-and-joint-health","drug-delivery-systems"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Bioactive glass/gelatin scaffolds loaded with CM11 antimicrobial peptide and zoledronic acid demonstrated both enhanced osteogenic stem cell differentiation and antimicrobial activity against MDR bacteria.","whyItMatters":"Post-surgical bone infections by drug-resistant bacteria are devastating and difficult to treat. A scaffold that simultaneously regrows bone and prevents infection could dramatically improve outcomes for patients needing bone reconstruction or implants.","specificNumbers":"Zoledronic acid at 4.00 mg/mL; CM11 peptide at 2x minimum inhibitory concentration; BG/Gel composite synthesized via sol-gel method.","methodology":"In vitro study synthesizing BG/Gel composites via sol-gel method, loading with CM11 peptide and zoledronic acid. Characterized by FTIR, SEM, and disk diffusion. Stem cell differentiation assessed by MTT, calcium/ALP assays, immunocytochemistry for osteocalcin, and RT-PCR for osteoblast markers.","limitations":"In vitro study only — no animal model testing of scaffold performance. Long-term peptide release kinetics and scaffold degradation not fully characterized. Clinical translation requires animal studies for biocompatibility and mechanical strength. Only tested against two bacterial species."},{"rthcId":"RPEP-09432","title":"The Role of Natriuretic Peptides in the Management of Heart Failure with a Focus on the Patient with Diabetes.","authors":"Vergani, Michela; Cannistraci, Rosa; Perseghin, Gianluca; Ciardullo, Stefano","year":2024,"journal":"Journal of clinical medicine, 13(20)","doi":"10.3390/jcm13206225","pmid":"39458174","tags":["natriuretic-peptides","heart-health","diabetes-and-blood-sugar","biomarkers-and-diagnostics"],"studyType":"review","evidenceStrength":"strong","keyFinding":"BNP and NT-proBNP are validated biomarkers for heart failure diagnosis and prognosis, with specific clinical thresholds for ruling out HF, and provide additional value in diabetic patients for cardiovascular risk stratification and treatment selection.","whyItMatters":"Heart failure in diabetic patients is common but often diagnosed late. Natriuretic peptide testing can identify at-risk patients before symptoms develop, enabling earlier use of protective medications and potentially preventing overt heart failure.","specificNumbers":"BNP and NT-proBNP have high negative predictive value for heart failure; international guidelines recommend their measurement.","methodology":"Clinical review synthesizing evidence on natriuretic peptide utility in heart failure management, incorporating the 2023 ESC consensus recommendations with focus on diabetes comorbidity.","limitations":"Review article — no new data. Natriuretic peptide interpretation is complicated by obesity (lower values), kidney disease (higher values), age, and sex. Not all clinical settings have access to rapid NP testing. Cut-off values may need population-specific adjustment."},{"rthcId":"RPEP-09433","title":"Beyond insulin: The Intriguing role of GLP-1 in Parkinson's disease.","authors":"Verma, Aanchal; Goyal, Ahsas","year":2024,"journal":"European journal of pharmacology, 982, 176936","doi":"10.1016/j.ejphar.2024.176936","pmid":"39182542","tags":["glp-1-receptor-agonists","brain-and-cognition","neuropeptides"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"GLP-1 receptor agonists show neuroprotective, anti-inflammatory, and neurotrophic properties in Parkinson's disease models, with the diabetes-PD link providing mechanistic rationale for therapeutic repurposing.","whyItMatters":"Parkinson's disease has no disease-modifying treatment — current drugs only manage symptoms. If GLP-1 agonists can slow neurodegeneration, they would be the first class to change the disease's trajectory, and they're already FDA-approved with established safety profiles.","specificNumbers":"GLP-1 is synthesized in several brain areas; acts through GLP-1 receptors to provide neuroprotection and reduce inflammation.","methodology":"Narrative review synthesizing preclinical and clinical evidence for GLP-1 receptor agonist neuroprotection in Parkinson's disease, examining mechanisms including anti-inflammation, neurotrophic support, and insulin signaling.","limitations":"Most evidence is preclinical. Early clinical data is limited and not yet definitive. The mechanisms of GLP-1-mediated neuroprotection in PD are not fully understood. Not all GLP-1RAs cross the blood-brain barrier equally. Optimal dosing for neuroprotection may differ from diabetes dosing."},{"rthcId":"RPEP-09434","title":"Exendin-4: A potential therapeutic strategy for Alzheimer's disease and Parkinson's disease.","authors":"Verma, Aanchal; Chaudhary, Shobhit; Solanki, Kunal; Goyal, Ahsas; Yadav, Harlokesh Narayan","year":2024,"journal":"Chemical biology & drug design, 103(1), e14426","doi":"10.1111/cbdd.14426","pmid":"38230775","tags":["glp-1-receptor-agonists","brain-and-cognition","neuropeptides","exenatide"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Exendin-4 demonstrates neuroprotective effects against both Alzheimer's and Parkinson's disease in preclinical models, operating through anti-inflammatory, anti-oxidative, and neurotrophic mechanisms.","whyItMatters":"Neither Alzheimer's nor Parkinson's has a disease-modifying treatment. Exendin-4 is already FDA-approved for diabetes, has a known safety profile, and shows brain-protective effects — making it a high-priority candidate for drug repurposing in neurodegenerative diseases.","specificNumbers":"Exendin-4 affects multiple neuroprotective pathways; millions affected worldwide by neurodegenerative disorders.","methodology":"Comprehensive narrative review synthesizing preclinical and clinical evidence for exendin-4's neuroprotective properties in Alzheimer's and Parkinson's disease models.","limitations":"Primarily preclinical evidence — human trial data is limited. Blood-brain barrier penetration of exendin-4 may limit its central nervous system effects. Optimal dosing for neuroprotection unknown. Multiple neurodegenerative disease mechanisms may not all be addressed by a single drug. Overlap with the GLP-1/Parkinson's review space."},{"rthcId":"RPEP-09435","title":"Innovative Strategies and Methodologies in Antimicrobial Peptide Design.","authors":"Verma, Devesh Pratap; Tripathi, Amit Kumar; Thakur, Ashwani Kumar","year":2024,"journal":"Journal of functional biomaterials, 15(11)","doi":"10.3390/jfb15110320","pmid":"39590524","tags":["antimicrobial-peptides","peptide-engineering"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Modern AMP design combines natural peptide template modification, structure-activity relationship analysis, and computational/AI-driven approaches to create optimized antimicrobial peptides with enhanced potency and selectivity.","whyItMatters":"Antibiotic resistance kills over 1.2 million people annually. Rationally designed AMPs offer a fundamentally different mechanism of action that is harder for bacteria to evolve resistance against — but getting the design right is critical for clinical translation.","specificNumbers":"AMPs found across various species; review covers identification, design, and optimization methodologies.","methodology":"Comprehensive review covering AMP occurrence across species, design methodologies including template modification, structure-function analysis, and computational approaches.","limitations":"Review article — no new experimental data. Many designed AMPs face challenges in stability, toxicity, and manufacturing cost. Translation from designed peptide to clinical drug remains a major bottleneck. Not all design strategies are equally validated."},{"rthcId":"RPEP-09436","title":"Cathelicidin antimicrobial peptide expression in neutrophils and neurons antagonistically modulates neuroinflammation.","authors":"Verma, Subash Chand; Enée, Emmanuelle; Manasse, Kanchanadevi; Rebhi, Feriel; Penc, Axelle; Romeo-Guitart, David; Bui Thi, Cuc; Titeux, Matthias; Oury, Franck; Fillatreau, Simon; Liblau, Roland; Diana, Julien","year":2024,"journal":"The Journal of clinical investigation, 135(3)","doi":"10.1172/JCI184502","pmid":"39656548","tags":["cathelicidins","antimicrobial-peptides","brain-and-cognition","autoimmune-conditions"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"Cathelicidin antimicrobial peptide has antagonistic roles in neuroinflammation: neutrophil-derived CRAMP promotes disease in EAE, while neuron-derived CRAMP is protective, demonstrating cell-type-specific immunomodulation.","whyItMatters":"Multiple sclerosis has no cure, and understanding what drives neuroinflammation is key to finding one. This study reveals that antimicrobial peptides — traditionally thought of as infection fighters — play complex, context-dependent roles in autoimmune brain disease.","specificNumbers":"CRAMP produced by CNS-recruited neutrophils at early stage; expressed by neurons with opposing effects on inflammation.","methodology":"Animal study using EAE (experimental autoimmune encephalomyelitis) mouse model of multiple sclerosis. Investigated cathelicidin (CRAMP) expression in CNS-recruited neutrophils and neurons, and assessed effects on disease progression.","limitations":"Mouse model (EAE) — may not fully replicate human MS. CRAMP (mouse) may have different properties than LL-37 (human cathelicidin). Mechanisms underlying the opposite effects not fully characterized. Translation to therapeutic approaches is unclear."},{"rthcId":"RPEP-09437","title":"Atrial Fibrillation and Semaglutide Effects in Obesity-Related Heart Failure With Preserved Ejection Fraction: STEP-HFpEF Program.","authors":"Verma, Subodh; Butler, Javed; Borlaug, Barry A; Davies, Melanie J; Kitzman, Dalane W; Petrie, Mark C; Shah, Sanjiv J; Jensen, Thomas Jon; Rasmussen, Søren; Rönnbäck, Cecilia; Merkely, Bela; O'Keefe, Evan; Kosiborod, Mikhail N","year":2024,"journal":"Journal of the American College of Cardiology, 84(17), 1603-1614","doi":"10.1016/j.jacc.2024.08.023","pmid":"39217565","tags":["glp-1-receptor-agonists","semaglutide","heart-health","obesity-and-weight-management"],"studyType":"RCT","evidenceStrength":"strong","keyFinding":"Semaglutide 2.4 mg improved HFpEF outcomes regardless of AF status, with greater symptom improvements in AF patients (KCCQ-CSS +11.5 vs +4.3 points; P interaction=0.001).","whyItMatters":"AF and HFpEF often coexist, and clinicians need to know if treatments work across both conditions. This analysis confirms semaglutide benefits are not diminished by AF — and may actually be amplified in this higher-risk subgroup.","specificNumbers":"Semaglutide 2.4 mg once weekly; STEP-HFpEF and STEP-HFpEF DM trials pooled; stratified by AF status.","methodology":"Pre-specified secondary analysis of pooled data from STEP-HFpEF and STEP-HFpEF DM randomized trials. 1,145 patients with HFpEF and BMI ≥30, randomized 1:1 to semaglutide 2.4 mg vs placebo for 52 weeks, stratified by AF history.","limitations":"Secondary/subgroup analysis — not powered for the AF subgroup comparison as a primary endpoint. AF history was investigator-reported, not adjudicated. AF types (paroxysmal, persistent, permanent) had varying sample sizes. 52-week follow-up may not capture long-term outcomes."},{"rthcId":"RPEP-09438","title":"Efficacy of Semaglutide by Sex in Obesity-Related Heart Failure With Preserved Ejection Fraction: STEP-HFpEF Trials.","authors":"Verma, Subodh; Butler, Javed; Borlaug, Barry A; Davies, Melanie; Kitzman, Dalane W; Shah, Sanjiv J; Petrie, Mark C; Barros, Eric; Rönnbäck, Cecilia; Vestergaard, Lene Sommer; Schou, Morten; Ezekowitz, Justin A; Sharma, Kavita; Patel, Shachi; Chinnakondepalli, Khaja M; Kosiborod, Mikhail N","year":2024,"journal":"Journal of the American College of Cardiology, 84(9), 773-785","doi":"10.1016/j.jacc.2024.06.001","pmid":"38913003","tags":["glp-1-receptor-agonists","semaglutide","heart-health","obesity-and-weight-management"],"studyType":"RCT","evidenceStrength":"strong","keyFinding":"Semaglutide 2.4 mg produced greater weight loss in women vs men (-9.6% vs -7.2%, P interaction=0.006) but equivalent HF symptom improvements (KCCQ-CSS ~+7.5 points) in obesity-related HFpEF.","whyItMatters":"More women than men have HFpEF, and sex-based differences in treatment response are poorly studied. This analysis confirms that semaglutide is effective for both sexes — and that women may derive even greater metabolic benefit from the weight loss component.","specificNumbers":"More women than men in the study population; semaglutide 2.4 mg weekly; consistent treatment effects across sexes.","methodology":"Prespecified secondary analysis of pooled STEP-HFpEF and STEP-HFpEF DM randomized trials. 1,145 patients (49.7% women) with HFpEF and BMI ≥30, randomized to semaglutide 2.4 mg vs placebo for 52 weeks, stratified by sex.","limitations":"Subgroup analysis — not independently powered for sex differences. Baseline differences between sexes may confound comparisons. The greater weight loss in women doesn't appear to translate to greater symptom improvement, raising questions about what mediates symptom benefit."},{"rthcId":"RPEP-09439","title":"Inflammation in Obesity-Related HFpEF: The STEP-HFpEF Program.","authors":"Verma, Subodh; Petrie, Mark C; Borlaug, Barry A; Butler, Javed; Davies, Melanie J; Kitzman, Dalane W; Shah, Sanjiv J; Rönnbäck, Cecilia; Abildstrøm, Steen Z; Liisberg, Karoline; Wolf, Dennis; von Lewinski, Dirk; Lelonek, Malgorzata; Melenovsky, Vojtech; Senni, Michele; Kosiborod, Mikhail N","year":2024,"journal":"Journal of the American College of Cardiology, 84(17), 1646-1662","doi":"10.1016/j.jacc.2024.08.028","pmid":"39217564","tags":["glp-1-receptor-agonists","semaglutide","heart-health","inflammation-and-immunity"],"studyType":"RCT","evidenceStrength":"strong","keyFinding":"Semaglutide reduced CRP independently of baseline inflammation level and weight loss magnitude in obesity-related HFpEF, suggesting direct anti-inflammatory effects beyond weight reduction.","whyItMatters":"This study reveals that semaglutide's anti-inflammatory effect is not simply a consequence of weight loss. It has independent anti-inflammatory properties that may be key to its heart failure benefits — opening new understanding of how GLP-1 drugs work.","specificNumbers":"Semaglutide 2.4 mg weekly reduced CRP levels; clinical benefits consistent across baseline CRP levels.","methodology":"Secondary analysis of pooled STEP-HFpEF and STEP-HFpEF DM trial data. 1,145 patients stratified by baseline CRP (<2, ≥2 to <10, ≥10 mg/L). Assessed treatment effects on KCCQ-CSS, weight, 6MWD, and CRP across CRP categories.","limitations":"Secondary subgroup analysis. CRP is a nonspecific inflammation marker — cannot identify specific inflammatory pathways. 52-week follow-up. Interaction tests may lack power to detect small differential effects. Cannot fully separate weight-loss-dependent from weight-loss-independent mechanisms."},{"rthcId":"RPEP-09440","title":"Effects of semaglutide, empagliflozin and their combination on renal diffusion-weighted MRI and total kidney volume in patients with type 2 diabetes: a post hoc analysis from a 32 week randomised trial.","authors":"Vernstrøm, Liv; Gullaksen, Søren; Sørensen, Steffen S; Ringgaard, Steffen; Laustsen, Christoffer; Birn, Henrik; Funck, Kristian L; Laugesen, Esben; Poulsen, Per L","year":2024,"journal":"Diabetologia, 67(10), 2175-2187","doi":"10.1007/s00125-024-06228-y","pmid":"39078489","tags":["glp-1-receptor-agonists","semaglutide","kidney-health"],"studyType":"RCT","evidenceStrength":"moderate","keyFinding":"Semaglutide and empagliflozin each reduced kidney cortical ADC and total kidney volume, but their combination did not show additive ADC effects; changes were independent of GFR, albuminuria, and inflammation.","whyItMatters":"Understanding how kidney-protective drugs work at the tissue level could optimize combination therapy strategies. The unexpected finding that combination therapy didn't enhance kidney MRI changes challenges assumptions about additive benefits.","specificNumbers":"32-week randomized trial; diffusion-weighted MRI and total kidney volume measured; semaglutide vs. empagliflozin vs. combination.","methodology":"Post hoc analysis of a 32-week randomized trial. 80 patients with T2D and high CV risk randomized to 4 groups (n=20 each): placebo, empagliflozin, semaglutide, or combination. Kidney ADC and total kidney volume measured by MRI.","limitations":"Small sample (20 per group). Post hoc analysis. ADC interpretation is debated — may not specifically reflect fibrosis. 32-week duration may be insufficient. Combination group had sequential rather than simultaneous drug initiation. ADC changes did not correlate with clinical endpoints."},{"rthcId":"RPEP-09441","title":"Obesity and Weight Loss Strategies for Patients With Heart Failure.","authors":"Vest, Amanda R; Schauer, Philip R; Rodgers, Jo E; Sanderson, Emily; LaChute, Courtney L; Seltz, Jessica; Lavie, Carl J; Mandras, Stacy A; Tang, W H Wilson; daSilva-deAbreu, Adrian","year":2024,"journal":"JACC. Heart failure, 12(9), 1509-1527","doi":"10.1016/j.jchf.2024.06.006","pmid":"39093256","tags":["glp-1-receptor-agonists","semaglutide","heart-health","obesity-and-weight-management"],"studyType":"review","evidenceStrength":"strong","keyFinding":"GLP-1 agonists (semaglutide) are confirmed safe and effective for weight loss in obesity-related HFpEF, but evidence for safety in advanced HFrEF is limited and warrants caution.","whyItMatters":"Obesity worsens heart failure prognosis, but weight loss options for HF patients have been limited and risky. The STEP-HFpEF results open a new treatment avenue for HFpEF, but clinicians need clear guidance on which HF patients are appropriate candidates.","specificNumbers":"Review covers HFrEF and HFpEF; highlights STEP-HFpEF program results with semaglutide; discusses bariatric surgery and lifestyle data.","methodology":"Clinical review covering obesity management in heart failure, including lifestyle, bariatric surgery, and pharmacotherapy with focus on GLP-1 and GIP/GLP-1 agonists.","limitations":"Review article — no new data. STEP-HFpEF data applies to HFpEF, not HFrEF. Safety concerns in HFrEF are based on smaller, earlier studies. Tirzepatide data in HF is emerging. Long-term weight maintenance after GLP-1 discontinuation in HF patients is unknown."},{"rthcId":"RPEP-09442","title":"The Synthetic Peptide LyeTx I mn∆K, Derived from Lycosa erythrognatha Spider Toxin, Is Active against Methicillin-Resistant Staphylococcus aureus (MRSA) In Vitro and In Vivo.","authors":"Vieira, Ana Paula Gonçalves Coelho; de Souza, Amanda Neves; Lima, William Gustavo; Brito, Julio Cesar Moreira; Simião, Daniela Carolina; Gonçalves, Lucas Vinícius Ribeiro; Cordeiro, Lídia Pereira Barbosa; de Oliveira Scoaris, Denise; Fernandes, Simone Odília Antunes; Resende, Jarbas Magalhães; Bechinger, Burkhard; Verly, Rodrigo Moreira; de Lima, Maria Elena","year":2024,"journal":"Antibiotics (Basel, Switzerland), 13(3)","doi":"10.3390/antibiotics13030248","pmid":"38534683","tags":["antimicrobial-peptides","venom-derived-peptides"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"The synthetic spider venom-derived peptide LyeTx I mn∆K demonstrated both in vitro activity (MIC/MBC) and in vivo efficacy against MRSA, with synergistic effects when combined with conventional antibiotics.","whyItMatters":"MRSA kills thousands annually and has few treatment options. Moving from lab to animal efficacy is the critical translational step that most antimicrobial peptides fail at. This peptide's in vivo success significantly advances its potential as a clinical candidate.","specificNumbers":"Tested MIC, MBC, synergy with other drugs, and in vivo efficacy against MRSA (specific values not detailed in abstract excerpt).","methodology":"Combined in vitro and animal study. Determined MIC, MBC, and synergy with antibiotics against MRSA. Tested in vivo efficacy in an animal infection model.","limitations":"Animal model results need human validation. Peptide stability, toxicity profile, and manufacturing scalability not fully addressed. Specific animal model details and dosing from abstract are limited. Combination antibiotic strategies need further optimization."},{"rthcId":"RPEP-09443","title":"[Translated article] Glucagon-Like Peptide-1 Agonists for Treating Obesity in Patients With Immune-Mediated Skin Diseases.","authors":"Vilarrasa, E; Nicolau, J; de la Cueva, P; Goday, A; Gallardo, F; Martorell-Calatayud, A; Carrascosa, J M","year":2024,"journal":"Actas dermo-sifiliograficas, 115(1), T56-T65","doi":"10.1016/j.ad.2023.10.019","pmid":"37918631","tags":["glp-1-receptor-agonists","inflammation-and-immunity","skin-and-wound-healing","obesity-and-weight-management"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"GLP-1 receptor agonists offer weight loss and potential anti-inflammatory benefits for patients with psoriasis or hidradenitis suppurativa complicated by obesity, addressing a key driver of disease severity.","whyItMatters":"Many psoriasis and HS patients are trapped in an obesity-inflammation cycle that worsens both conditions. GLP-1 drugs could break this cycle by reducing both weight and inflammation — a dual benefit that existing dermatology treatments don't provide.","specificNumbers":"GLP-1 drugs produce greater weight loss than previous pharmacological options; psoriasis and HS are often associated with obesity.","methodology":"Clinical review covering pharmacological obesity management in immune-mediated skin diseases, with focus on GLP-1 agonist mechanisms and clinical evidence.","limitations":"Review article — no clinical trial data specific to GLP-1 use in dermatology patients. Direct anti-inflammatory effects on skin diseases are theoretical. Insurance coverage for GLP-1 drugs is often limited to diabetes/obesity indications. Long-term weight maintenance and skin disease outcomes unknown."},{"rthcId":"RPEP-09444","title":"Identification of the Bioavailable Peptidome of Chia Protein Hydrolysate and the In Silico Evaluation of Its Antioxidant and ACE Inhibitory Potential.","authors":"Villanueva, Alvaro; Rivero-Pino, Fernando; Martin, Maria E; Gonzalez-de la Rosa, Teresa; Montserrat-de la Paz, Sergio; Millan-Linares, Maria C","year":2024,"journal":"Journal of agricultural and food chemistry, 72(6), 3189-3199","doi":"10.1021/acs.jafc.3c05331","pmid":"38305180","tags":["food-derived-peptides","ace-inhibitory-peptides","antioxidant-peptides"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Four bioavailable peptides from chia protein hydrolysate were identified through absorption modeling and computational analysis as primary contributors to antioxidant and ACE inhibitory bioactivities.","whyItMatters":"Identifying which specific peptides survive digestion, get absorbed, and reach target tissues is critical for understanding how food-derived peptides actually work in the body — moving beyond 'chia is healthy' to understanding exactly why.","specificNumbers":"Alcalase enzyme used for hydrolysis; bioavailable peptidome characterized; in silico evaluation of antioxidant and ACE inhibitory potential.","methodology":"In vitro/in silico study. Chia protein hydrolyzed with Alcalase, intestinal absorption simulated using Caco-2 cell transwell model, peptides identified by mass spectrometry, and bioactivity predicted using computational tools.","limitations":"In vitro absorption model — may not fully replicate human intestinal absorption. In silico bioactivity predictions need experimental validation. Single enzyme (Alcalase) used — different digestion conditions may yield different peptides. Actual plasma concentrations and tissue delivery not measured."},{"rthcId":"RPEP-09445","title":"GLP-1-ra and heart failure-related outcomes in patients with and without history of heart failure: an updated systematic review and meta-analysis.","authors":"Villaschi, Alessandro; Ferrante, Giuseppe; Cannata, Francesco; Pini, Daniela; Pagnesi, Matteo; Corrada, Elena; Reimers, Bernhard; Mehran, Roxana; Federici, Massimo; Savarese, Gianluigi; Metra, Marco; Condorelli, Gianluigi; Stefanini, Giulio G; Chiarito, Mauro","year":2024,"journal":"Clinical research in cardiology : official journal of the German Cardiac Society, 113(6), 898-909","doi":"10.1007/s00392-023-02362-6","pmid":"38252145","tags":["glp-1-receptor-agonists","heart-health","diabetes-and-blood-sugar"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"GLP-1 RAs reduced HF hospitalization (HR 0.79) and CV death (HR 0.81) only in patients without HF history, while reducing MACE equally regardless of HF history (HR 0.86 no HF, 0.83 with HF).","whyItMatters":"This clarifies a crucial clinical question: GLP-1 drugs prevent heart failure but may not treat it. Clinicians should use GLP-1RAs early in high-risk patients to prevent HF, while recognizing these drugs may not reduce HF-specific events in patients who already have established heart failure.","specificNumbers":"Meta-analysis of all randomized placebo-controlled GLP-1RA trials with CV outcomes reported; stratified by HF history vs. no HF history.","methodology":"Systematic review and meta-analysis of 10 randomized, placebo-controlled GLP-1RA trials (68,653 patients), stratified by heart failure history. Random-effects model. PROSPERO-registered (CRD42022371264). Primary outcome: HF hospitalizations.","limitations":"Subgroup analysis across trials — individual trials were not powered for HF subgroup comparisons. Different GLP-1RAs pooled together. HF definitions may vary across trials. Cannot distinguish between HFpEF and HFrEF in most trials. Follow-up durations varied."},{"rthcId":"RPEP-09446","title":"Virtual Screening of Peptide Libraries: The Search for Peptide-Based Therapeutics Using Computational Tools.","authors":"Vincenzi, Marian; Mercurio, Flavia Anna; Leone, Marilisa","year":2024,"journal":"International journal of molecular sciences, 25(3)","doi":"10.3390/ijms25031798","pmid":"38339078","tags":[],"studyType":"review","evidenceStrength":"n/a","keyFinding":"This review surveys computational virtual screening methods used to discover therapeutic peptides from large libraries. Structure-based virtual screening (SBVS) is highlighted as a cost-effective approach to identify peptides that can target 'undruggable' proteins — those with large, flat surfaces that small molecule drugs cannot easily bind. The review covers applications across anticancer peptides, antimicrobial/antiviral peptides, and peptides that block amyloid fiber formation, while also addressing the challenges of using peptides as drugs (stability, delivery, bioavailability).","whyItMatters":"Finding therapeutic peptides traditionally required screening millions of candidates in expensive lab experiments. Computational virtual screening dramatically reduces this cost by predicting which peptides are most likely to work before any lab testing begins. As peptide therapeutics become more important, these computational methods are accelerating drug discovery across cancer, infectious disease, and neurodegeneration.","specificNumbers":"","methodology":"Literature review of computational approaches to peptide library screening, with focus on structure-based virtual screening (SBVS) strategies and their applications to diverse bioactive peptide classes.","limitations":"This is a methods review, not a study with original data. Computational predictions require experimental validation, and virtual screening hit rates vary widely. The review may not cover the most recent AI/machine learning approaches that are rapidly evolving in this space."},{"rthcId":"RPEP-09447","title":"Absorption of bioactive peptides following collagen hydrolysate intake: a randomized, double-blind crossover study in healthy individuals.","authors":"Virgilio, Nicolina; Schön, Christiane; Mödinger, Yvonne; van der Steen, Bastiaan; Vleminckx, Sara; van Holthoon, Frédérique L; Kleinnijenhuis, Anne J; Silva, Catarina I F; Prawitt, Janne","year":2024,"journal":"Frontiers in nutrition, 11, 1416643","doi":"10.3389/fnut.2024.1416643","pmid":"39149544","tags":["collagen-peptides","food-derived-peptides","oral-peptide-delivery"],"studyType":"RCT","evidenceStrength":"moderate","keyFinding":"All collagen hydrolysate sources (fish, porcine, bovine) at different molecular weights yielded comparable plasma concentrations of free and peptide-bound hydroxyproline, confirming bioavailability of intact collagen peptides.","whyItMatters":"The collagen supplement market is massive but bioavailability has been questioned. This study provides clinical evidence that collagen peptides survive digestion and enter the bloodstream — regardless of animal source — validating the supplement category's core premise.","specificNumbers":"Fish, porcine, and bovine collagen sources tested; bovine at 2,000 and 5,000 Da molecular weights; single-dose crossover design; plasma amino acids and peptides measured.","methodology":"Randomized, double-blind crossover clinical study in healthy volunteers. Single-dose bioavailability assessed by measuring plasma free and peptide-bound hydroxyproline and selected collagen peptides after intake of different CH sources.","limitations":"Single-dose study — chronic intake effects not assessed. Healthy volunteers only — absorption may differ in elderly or diseased populations. Plasma levels measured, but actual tissue delivery (skin, joints, bones) not confirmed. Small study size implied. Ideal plasma levels for biological effects are unknown."},{"rthcId":"RPEP-09448","title":"Effects of prophylactic drug therapies and anti-calcitonin peptide-related monoclonal antibodies on subjective sleep quality: An Italian multicenter study.","authors":"Viticchi, Giovanna; Di Stefano, Vincenzo; Altamura, Claudia; Falsetti, Lorenzo; Torrente, Angelo; Brunelli, Nicoletta; Salvemini, Sergio; Alonge, Paolo; Bartolini, Marco; Di Felice, Chiara; Adragna, Maria Stella; Moroncini, Gianluca; Vernieri, Fabrizio; Brighina, Filippo; Silvestrini, Mauro","year":2024,"journal":"Sleep medicine, 117, 87-94","doi":"10.1016/j.sleep.2024.03.026","pmid":"38518587","tags":["cgrp","pain-management","sleep-and-circadian-peptides"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Anti-CGRP mAbs produced the greatest improvement in PSQI sleep scores (mean difference 1.49, p=0.010) compared to oral prophylactic therapies in a 3-month multicenter study of 214 migraine patients.","whyItMatters":"Sleep disruption is both a trigger and consequence of migraine. Treatments that improve both migraine and sleep could break this cycle more effectively than those targeting only headache frequency.","specificNumbers":"Multicenter Italian study; compared oral prophylactics vs. anti-CGRP mAbs on sleep quality (specific metrics not detailed in abstract excerpt).","methodology":"Prospective multicenter study at 3 Italian headache centers. 214 migraine patients assigned to first-line oral drugs or anti-CGRP mAbs. PSQI and MIDAS scales administered at baseline and 3 months.","limitations":"Non-randomized assignment to treatment groups. 3-month follow-up — long-term sleep effects unknown. PSQI is subjective. No objective sleep measures (polysomnography, actigraphy). Open-label design may introduce placebo effects."},{"rthcId":"RPEP-09449","title":"Understanding the Biological Relationship between Migraine and Depression.","authors":"Viudez-Martínez, Adrián; Torregrosa, Abraham B; Navarrete, Francisco; García-Gutiérrez, María Salud","year":2024,"journal":"Biomolecules, 14(2)","doi":"10.3390/biom14020163","pmid":"38397400","tags":["cgrp","neuropeptides","mental-health-peptides","pain-management"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Multiple neuropeptide systems (CGRP, PACAP, substance P, neuropeptide Y, orexins) provide overlapping biological substrates for both migraine and depression, explaining their strong bidirectional clinical relationship.","whyItMatters":"Treating migraine without addressing depression (and vice versa) leads to poorer outcomes. Understanding shared neuropeptide mechanisms could enable dual-action therapies — drugs that treat both conditions by targeting common pathways like CGRP or PACAP.","specificNumbers":"Migraine patients are 2.5x more likely to develop depression; risk is higher in chronic migraine and migraine with aura; bidirectional relationship.","methodology":"Comprehensive narrative review of epidemiological, clinical, and molecular evidence linking migraine and depression through shared biological mechanisms.","limitations":"Narrative review — no new data. Causation vs correlation for shared mechanisms is difficult to establish. Not all migraine patients have depression and vice versa. Individual neuropeptide contributions to each condition are not fully quantified."},{"rthcId":"RPEP-09450","title":"Influence of collagen peptide supplementation on visible signs of skin and nail health and -aging in an East Asian population: A double blind, randomized, placebo-controlled trial.","authors":"Vleminckx, Sara; Virgilio, Nicolina; Asserin, Jerome; Prawitt, Janne; Silva, Catarina I F","year":2024,"journal":"Journal of cosmetic dermatology, 23(11), 3645-3653","doi":"10.1111/jocd.16458","pmid":"39143887","tags":["collagen-peptides","skin-and-wound-healing"],"studyType":"RCT","evidenceStrength":"moderate","keyFinding":"5g daily collagen peptide supplementation significantly improved dermis density and skin moisture at 84 days, with visible improvements in wrinkles, elasticity, and nail color appearing by day 28 in East Asian women.","whyItMatters":"The collagen supplement market exceeds billions of dollars, but high-quality clinical evidence — especially in specific ethnic populations — has been limited. This RCT provides rigorous evidence that collagen peptides produce measurable skin improvements in East Asian women.","specificNumbers":"85 women; ages 43-65; 5g collagen peptides daily; double-blind placebo-controlled design.","methodology":"Double-blind, randomized, placebo-controlled trial. 85 healthy women (43-65 years) randomized to collagen peptides (5g) or maltodextrin placebo. Standardized face cream used by both groups. Skin parameters assessed at baseline, day 28, and day 84.","limitations":"85 participants is moderate for an RCT. Single ethnic population. 84-day study — long-term maintenance unknown. Standardized cream use may confound some comparisons. Industry-funded (collagen manufacturer). Beauty perception is subjective. Nail outcomes are exploratory."},{"rthcId":"RPEP-09451","title":"Genetic variability of incretin receptors affects the occurrence of neurodegenerative diseases and their characteristics.","authors":"Vogrinc, David; Redenšek Trampuž, Sara; Blagus, Tanja; Trošt, Maja; Gregorič Kramberger, Milica; Emeršič, Andreja; Čučnik, Saša; Goričar, Katja; Dolžan, Vita","year":2024,"journal":"Heliyon, 10(20), e39157","doi":"10.1016/j.heliyon.2024.e39157","pmid":"39506938","tags":["glp-1-receptor-agonists","gip","brain-and-cognition"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"GLP1R rs10305420 genotype was associated with increased odds of both AD and PD, GLP1R variants correlated with AD CSF biomarkers, and GIPR rs1800437 was associated with dementia development in PD (OR 1.95).","whyItMatters":"This is genetic evidence that the same receptor systems targeted by blockbuster diabetes drugs play a role in neurodegeneration. Patients with specific GLP1R/GIPR variants may be at higher neurodegenerative risk — and potentially better candidates for GLP-1/GIP drug neuroprotection.","specificNumbers":"AD and PD patients studied; GLP1R and GIPR genetic variability assessed in relation to disease phenotypes.","methodology":"Case-control genetic study. AD patients, PD patients, and healthy controls genotyped for GLP1R rs10305420, GLP1R rs6923761, and GIPR rs1800437. CSF biomarkers measured in AD; cognitive function assessed in PD.","limitations":"Observational genetic association study — cannot prove causation. Sample sizes not specified in abstract. Population-specific genetic frequencies may limit generalizability. Functional impact of these SNPs on receptor signaling not directly assessed."},{"rthcId":"RPEP-09452","title":"Phase 1 trial supports safety and mechanism of action of peptide immunotherapy for peanut allergy.","authors":"Voskamp, Astrid L; Khosa, Sugandhika; Phan, Tracy; DeBerg, Hannah A; Bingham, Judy; Hew, Mark; Smith, William; Abramovitch, Jodie; Rolland, Jennifer M; Moyle, Matthew; Nadeau, Kari C; Lack, Gideon; Larché, Mark; Wambre, Erik; O'Hehir, Robyn E; Hickey, Pascal; Prickett, Sara R","year":2024,"journal":"Allergy, 79(2), 485-498","doi":"10.1111/all.15966","pmid":"38112286","tags":["immune-system-peptides","vaccine-peptides","peptide-therapeutics"],"studyType":"RCT","evidenceStrength":"moderate","keyFinding":"PVX108 peptide immunotherapy was safe in peanut-allergic adults with no hypersensitivity events, and produced durable peanut-specific T-cell modulation (decreased ST2+ Th2A:CCR6+ Th17-like ratio) persisting to 18 months.","whyItMatters":"Peanut allergy has no cure, and current immunotherapy carries significant risk. Peptide-based immunotherapy that's safe enough to avoid allergic reactions while still reprogramming the immune system could transform food allergy treatment for millions of patients worldwide.","specificNumbers":"7 short peptides representing immunodominant T-cell epitopes of major peanut allergens; Phase 1 safety trial.","methodology":"First-in-human, randomized, double-blind, placebo-controlled Phase 1 trial. Single and repeat doses in peanut-allergic adults (46 active, 21 placebo). Safety and tolerability assessed; exploratory immunological analyses at pre-dose, Week 21, and Month 18.","limitations":"Phase 1 trial — safety and immune modulation shown, but clinical efficacy (food challenge outcomes) not yet demonstrated. Small sample size. No food challenge performed. Translation from immune biomarker changes to clinical protection needs Phase 2 confirmation."},{"rthcId":"RPEP-09453","title":"Duodenocolic fistula healing by pentadecapeptide BPC 157 in rats. A cytoprotection viewpoint.","authors":"Vukusic, D; Zenko Sever, A; Sever, M; Drmic, D; Milavic, M; Sikiric, S; Rasic, D; Krezic, I; Gojkovic, S; Prtoric, A; Bubalo, P; Coric, L; Dobric, I; Boban Blagaic, A; Rasic, Z; Skrtic, A; Seiwerth, S; Sikiric, P","year":2024,"journal":"Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 75(1)","doi":"10.26402/jpp.2024.1.09","pmid":"38583442","tags":["bpc-157","gut-health-peptides","peptide-therapeutics"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"BPC-157 healed duodenocolic fistulas in rats by rapidly inducing vessel recruitment at both fistula sides, with complete defect closure, no leakage, no weight loss, and favorable gene expression changes (elevated NOS-2, decreased COX-2/VEGF-A/NF-κB).","whyItMatters":"Gastrointestinal fistulas are notoriously difficult to heal and often require complex surgery. A peptide that can induce rapid vascular repair from both sides of a fistula represents a potentially transformative non-surgical approach to this challenging clinical problem.","specificNumbers":"BPC 157 at 10 µg/kg and 10 ng/kg; assessed at 3, 6, 9, 12, and 15 minutes after fistula creation; effective both locally and intragastrically.","methodology":"Animal study in rats with surgically created duodenocolic fistulas. BPC-157 given locally, intragastrically (10 μg/kg, 10 ng/kg), or intraperitoneally. Acute vascular response assessed at 3-15 min. Chronic healing assessed at days 1-28. Gene expression by mRNA analysis.","limitations":"Animal study in rats — human fistula healing may differ significantly. BPC-157 is not FDA-approved. Surgically created fistulas may not replicate disease-caused fistulas (Crohn's, radiation, etc.). Mechanism of rapid vessel recruitment not fully explained. No clinical trials for this indication."},{"rthcId":"RPEP-09454","title":"Cell-penetrating peptide and cationic liposomes mediated siRNA delivery to arrest growth of chronic myeloid leukemia cells in vitro.","authors":"Vysochinskaya, Vera; Zabrodskaya, Yana; Dovbysh, Olesya; Emelyanov, Anton; Klimenko, Vladimir; Knyazev, Nikolay; Terterov, Ivan; Egorova, Marya; Bogdanov, Alexey; Maslov, Michael; Vasin, Andrey; Dubina, Michael","year":2024,"journal":"Biochimie, 221, 1-12","doi":"10.1016/j.biochi.2024.01.006","pmid":"38215931","tags":["cell-penetrating-peptides","drug-delivery-systems","cancer-related-peptides"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Both EB1 cell-penetrating peptide and PEG-cationic liposomes delivered anti-BCR-ABL1 siRNA into CML K562 cells, with liposomes producing more effective gene silencing and proliferation inhibition.","whyItMatters":"Drug resistance in CML is a serious clinical problem. Gene-silencing therapy targeting BCR-ABL1 could bypass resistance mechanisms entirely, and developing effective delivery systems is the key barrier to making this approach clinically viable.","specificNumbers":"siRNA targeting BCR-ABL1; CPP + cationic liposome delivery system; growth arrest demonstrated in CML cells in vitro.","methodology":"In vitro study comparing EB1 peptide and 2X3-DOPE-DSPE-PEG2000 liposomes for siRNA delivery into K562 human CML cells. Gene expression and cell proliferation assessed.","limitations":"In vitro study in a single CML cell line (K562). No in vivo testing. Liposomes outperformed peptide delivery for this application. Clinical translation requires animal studies for toxicity, distribution, and efficacy. Durability of gene silencing not assessed."},{"rthcId":"RPEP-09455","title":"Psychiatric Safety of Semaglutide for Weight Management in People Without Known Major Psychopathology: Post Hoc Analysis of the STEP 1, 2, 3, and 5 Trials.","authors":"Wadden, Thomas A; Brown, Gregory K; Egebjerg, Christina; Frenkel, Ofir; Goldman, Bryan; Kushner, Robert F; McGowan, Barbara; Overvad, Maria; Fink-Jensen, Anders","year":2024,"journal":"JAMA internal medicine, 184(11), 1290-1300","doi":"10.1001/jamainternmed.2024.4346","pmid":"39226070","tags":["glp-1-receptor-agonists","semaglutide","mental-health-peptides","safety-and-side-effects"],"studyType":"RCT","evidenceStrength":"strong","keyFinding":"Semaglutide 2.4 mg did not increase depression (PHQ-9 treatment difference -0.56, p<0.001) or suicidal ideation (≤1% both groups) vs placebo across STEP 1, 2, 3, and 5 trials in participants without major psychopathology.","whyItMatters":"Media reports and regulatory inquiries raised concerns about GLP-1 drugs and mental health. This analysis of the largest semaglutide weight management dataset provides robust evidence that semaglutide is psychiatrically safe — and may even slightly improve mood.","specificNumbers":"Pooled data from STEP 1, 2, 3, and 5 trials; semaglutide 2.4 mg weekly vs. placebo; psychiatric adverse events assessed.","methodology":"Post hoc analysis of pooled data from 4 randomized, double-blind, placebo-controlled STEP trials (3,377 from STEP 1-3 at 68 weeks + 304 from STEP 5 at 104 weeks). PHQ-9 for depression, Columbia-Suicide Severity Rating Scale for suicidal ideation.","limitations":"Post hoc analysis — not designed as a psychiatric safety trial. Excluded participants with known major psychopathology at baseline. PHQ-9 improvement of -0.56 is statistically significant but not clinically meaningful. Short to medium follow-up. Does not address patients with pre-existing mental health conditions."},{"rthcId":"RPEP-09456","title":"Effectiveness of pharmacological interventions for managing obesity in children and adolescents: A systematic review and meta-analysis framed using minimal important difference estimates based on GRADE guidance to inform a clinical practice guideline.","authors":"Wahi, Gita; St-Pierre, Julie; Johnston, Bradley C; Fitzpatrick-Lewis, Donna; Usman, Ali; Sherifali, Diana; Merdad, Roah; Esmaeilinezhad, Zahra; Birken, Catherine S; Hamilton, Jill; Henderson, Mélanie; Moore, Sarah A; Ball, Geoff D C; Morrison, Katherine M","year":2024,"journal":"Pediatric obesity, 19(11), e13169","doi":"10.1111/ijpo.13169","pmid":"39238400","tags":["glp-1-receptor-agonists","obesity-and-weight-management"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Semaglutide produced the largest BMI z-score reduction (very large effect), largest triglyceride reduction, and meaningful quality-of-life improvement among pediatric obesity pharmacotherapies in a meta-analysis of 35 RCTs.","whyItMatters":"Childhood obesity is a global crisis with limited pharmacological options. This meta-analysis establishes the evidence hierarchy among available drugs and positions semaglutide as the most effective option — informing clinical guidelines and treatment decisions.","specificNumbers":"RCTs through November 2022; under-18 participants; assessed PROMs, cardiometabolic risk factors, anthropometry, and adverse events.","methodology":"Systematic review and meta-analysis of 35 RCTs in children <18 years. GRADE certainty of evidence assessed. Effects presented relative to minimal important differences. Agents: metformin (26 RCTs), GLP-1RAs (7 RCTs), orlistat (2 RCTs).","limitations":"Limited number of GLP-1RA trials (especially semaglutide — only 1 RCT). Short intervention durations (3-24 months). Few studies assessed patient-reported outcomes. Long-term effectiveness and safety of GLP-1RAs in children not yet established. Heterogeneity across trials."},{"rthcId":"RPEP-09457","title":"Synthetic exendin-4 disrupts responding to reward predictive incentive cues in male rats.","authors":"Wakabayashi, Ken T; Baindur, Ajay N; Feja, Malte; Suarez, Mauricio; Chen, Karie; Bernosky-Smith, Kimberly; Bass, Caroline E","year":2024,"journal":"Frontiers in behavioral neuroscience, 18, 1363497","doi":"10.3389/fnbeh.2024.1363497","pmid":"38549620","tags":["glp-1-receptor-agonists","exenatide","brain-and-cognition"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"Exendin-4 dose-dependently attenuated responding to incentive cues (reward-predictive stimuli) in rats without affecting free consumption of small sucrose volumes, suggesting GLP-1R activation modulates cue-driven motivation rather than just palatability.","whyItMatters":"This research reveals that GLP-1 drugs don't just reduce appetite — they change how the brain processes environmental cues that trigger wanting. This mechanism is relevant not only to obesity (where food cues drive overeating) but potentially to addiction (where drug cues drive relapse).","specificNumbers":"Three doses tested: 0.6, 1.2, and 2.4 µg/kg exendin-4 (i.p.); male rats; incentive cue responding task.","methodology":"Animal behavioral pharmacology study. Rats performed an incentive cue task (nosepoke during reward-predictive cue for sucrose). Exendin-4 at 0.6, 1.2, and 2.4 μg/kg i.p. tested on cue responding, latencies, and sucrose consumption.","limitations":"Animal study in male rats only — sex differences likely. Sucrose as reward model — may not generalize to all reward types. Pharmacokinetic interactions between dose and session time complicate interpretation. Cannot directly extrapolate dose-response to human clinical doses."},{"rthcId":"RPEP-09458","title":"Weight management medications for chronic use in 37 veterans affairs medical centers-A medication use evaluation.","authors":"Walczuk, Samantha; Burk, Muriel; Furmaga, Elaine; Ghassemi, Samaneh; McCarren, Madeline; Bukowski, Kenneth; Glassman, Peter; Cunningham, Fran","year":2024,"journal":"Obesity science & practice, 10(5), e70002","doi":"10.1002/osp4.70002","pmid":"39219745","tags":["glp-1-receptor-agonists","semaglutide","liraglutide","obesity-and-weight-management"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Real-world weight loss with GLP-1RAs (semaglutide, liraglutide) and other weight management medications at 37 VA centers was smaller than clinical trials, with higher discontinuation rates and barriers including drug shortages.","whyItMatters":"Clinical trials select ideal patients and ensure compliance. This real-world data shows what actually happens when weight loss drugs are prescribed to a diverse veteran population — providing pragmatic expectations for clinicians and patients.","specificNumbers":"37 VA medical centers; 6 medications evaluated; weight loss assessed at 3, 6, 12, and >12 months.","methodology":"Retrospective, cross-sectional medication use evaluation using electronic health records from 37 VA Medical Centers (March 2020 - March 2022). 1,959 veterans newly initiated on WMMs. Weight loss tracked at 3, 6, 12, and 12+ months.","limitations":"Retrospective chart review — adherence and dosing may be inconsistently documented. VA population skews male and older. COVID-19 pandemic period may have affected results. Drug shortages during study period limited semaglutide access. No comparison to non-pharmacological weight management."},{"rthcId":"RPEP-09459","title":"Real-world effectiveness of fremanezumab in patients with migraine switching from another mAb targeting the CGRP pathway.","authors":"Waliszewska-Prosół, Marta; Martelletti, Paolo","year":2024,"journal":"Dental and medical problems, 61(1), 9-11","doi":"10.17219/dmp/174706","pmid":"38284301","tags":["cgrp","pain-management"],"studyType":"cohort","evidenceStrength":"preliminary","keyFinding":"42.8% of migraine patients who failed prior CGRP mAb therapy achieved ≥50% reduction in monthly migraine days after switching to fremanezumab in the real-world Finesse Study.","whyItMatters":"Many migraine patients are told they've 'failed CGRP therapy' after one antibody doesn't work. This data shows that switching between receptor-targeting and ligand-targeting antibodies can rescue nearly half of these patients — expanding treatment options significantly.","specificNumbers":"Subgroup analysis from the Finesse Study; patients who switched from erenumab, galcanezumab, or eptinezumab to fremanezumab.","methodology":"Subgroup analysis of the Finesse Study, a real-world effectiveness study of fremanezumab. 153 patients with documented prior failure of another CGRP-pathway monoclonal antibody were analyzed.","limitations":"Subgroup analysis — not a dedicated switching trial. Open-label, non-randomized design. 153 patients is moderate for subgroup analysis. Response definition (≥50% reduction) may miss meaningful partial responders. Reasons for prior mAb failure varied."},{"rthcId":"RPEP-09460","title":"Understanding the efficacy and tolerability of migraine treatment: a deep dive into CGRP antagonists.","authors":"Waliszewska-Prosół, Marta; Raffaelli, Bianca; Straburzyński, Marcin; Martelletti, Paolo","year":2024,"journal":"Expert review of clinical pharmacology, 17(11), 1039-1051","doi":"10.1080/17512433.2024.2417655","pmid":"39412063","tags":["cgrp","pain-management"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"CGRP-targeting drugs (gepants and monoclonal antibodies) offer superior efficacy and tolerability compared to traditional migraine therapies, representing a transformative treatment advance with remaining questions about optimization and access.","whyItMatters":"CGRP drugs have transformed migraine care for millions, but many patients still lack access. The review highlights that both the successes and limitations of these therapies need to be understood for optimal clinical application.","specificNumbers":"Review covers both small-molecule CGRP receptor antagonists (gepants) and monoclonal antibodies (4 available); examines efficacy and tolerability data.","methodology":"Narrative review covering CGRP pathophysiology in migraine, clinical evidence for CGRP-targeted treatments, and open questions for clinical practice.","limitations":"Narrative review — no new data. Does not quantify specific efficacy numbers. Open questions about long-term safety, optimal switching strategies, and biomarkers for response prediction are acknowledged but not answered."},{"rthcId":"RPEP-09461","title":"Marine-Derived Peptides with Anti-Hypertensive Properties: Prospects for Pharmaceuticals, Supplements, and Functional Food.","authors":"Walquist, Mari Johannessen; Eilertsen, Karl-Erik; Elvevoll, Edel Oddny; Jensen, Ida-Johanne","year":2024,"journal":"Marine drugs, 22(4)","doi":"10.3390/md22040140","pmid":"38667757","tags":["food-derived-peptides","ace-inhibitory-peptides","antioxidant-peptides"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Marine invertebrates contain peptides with documented ACE-inhibitory and anti-hypertensive activity, but translation to human therapeutics requires more clinical studies and standardized assessment methods.","whyItMatters":"Marine environments contain vast biodiversity with therapeutic potential. Identifying anti-hypertensive peptides from sustainable marine sources could provide natural alternatives to synthetic blood pressure medications with fewer side effects.","specificNumbers":"Review covers peptides from various marine organisms; multiple mechanisms of anti-hypertensive action discussed.","methodology":"Comprehensive review of anti-hypertensive peptides from marine invertebrate phyla, covering extraction methods, assessment techniques, in vitro and in vivo evidence.","limitations":"Review highlights that most evidence is in vitro or animal-based. Diverse assessment methods complicate cross-study comparison. Many marine species remain unstudied. Sustainability of marine sourcing is a concern. Bioavailability of marine peptides after oral intake is uncertain."},{"rthcId":"RPEP-09462","title":"Conditional Cell-Penetrating Peptide Exposure as Selective Nanoparticle Uptake Signal.","authors":"Walter, Melanie; Bresinsky, Merlin; Zimmer, Oliver; Pockes, Steffen; Goepferich, Achim","year":2024,"journal":"ACS applied materials & interfaces, 16(29), 37734-37747","doi":"10.1021/acsami.4c07821","pmid":"39010308","tags":["cell-penetrating-peptides","drug-delivery-systems"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Conditional cell-penetrating peptide exposure on nanoparticles achieved 18-fold uptake improvement in ACE2-positive target cells compared to unmodified particles, without triggering receptor-mediated signaling.","whyItMatters":"Current targeted drug delivery often relies on receptor binding, which can trigger harmful signaling in cells. This conditional CPP approach offers receptor-independent cell entry that only activates at the target — potentially reducing side effects while dramatically improving drug delivery to tumors or diseased tissues.","specificNumbers":"Nanoparticles with conditional CPP exposure; receptor-independent uptake mechanism demonstrated.","methodology":"Researchers synthesized PLGA/PLA-PEG core-shell nanoparticles with TAT peptide on shorter PEG chains (2 kDa) and ACE2 inhibitor MLN-4760 on longer PEG chains (5 kDa). They evaluated nanoparticle stability, zeta potential, and cellular uptake in ACE2-positive vs. ACE2-negative cell lines.","limitations":"This is an in vitro proof-of-concept — the system hasn't been tested in living animals yet. The manufacturing complexity of dual-layer PEG nanoparticles could be challenging to scale. The ACE2-targeting approach was chosen as a model system; whether the conditional exposure mechanism works equally well with other receptor targets needs verification."},{"rthcId":"RPEP-09463","title":"Negative lipid membranes enhance the adsorption of TAT-decorated elastin-like polypeptide micelles.","authors":"Walter, Vivien; Schmatko, Tatiana; Muller, Pierre; Schroder, André P; MacEwan, Sarah R; Chilkoti, Ashutosh; Marques, Carlos M","year":2024,"journal":"Biophysical journal, 123(7), 901-908","doi":"10.1016/j.bpj.2024.03.001","pmid":"38449310","tags":["cell-penetrating-peptides","drug-delivery-systems","peptide-engineering"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"TAT-functionalized elastin-like polypeptide micelles showed enhanced and stepwise charge-dependent adsorption to negatively charged lipid membranes, recovering the membrane affinity lost when CPPs carry molecular cargo.","whyItMatters":"Cancer cells typically have more negatively charged membranes than healthy cells. A delivery system that preferentially binds negative membranes could naturally target tumors. This study reveals the fundamental biophysics governing how CPP-decorated carriers interact with charged membranes, informing smarter drug delivery design.","specificNumbers":"TAT peptide added to ELP block copolymer micelles; tested against negatively charged vs. neutral lipid membranes.","methodology":"Biophysical study using giant unilamellar vesicles (GUVs) with controlled lipid charge compositions. Measured binding constants of TAT-ELPBC micelles to neutral vs. negatively charged membranes using fluorescence microscopy.","limitations":"Model membrane study using artificial vesicles — real cell membranes are far more complex with proteins, sugars, and mixed lipids. The micelles adsorbed but did not translocate through membranes. Actual cancer cell targeting and drug delivery efficacy not tested."},{"rthcId":"RPEP-09464","title":"Machine learning for antimicrobial peptide identification and design.","authors":"Wan, Fangping; Wong, Felix; Collins, James J; de la Fuente-Nunez, Cesar","year":2024,"journal":"Nature reviews bioengineering, 2(5), 392-407","doi":"10.1038/s44222-024-00152-x","pmid":"39850516","tags":["antimicrobial-peptides","peptide-engineering"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Machine learning approaches can now predict antimicrobial activity, design novel peptides, and optimize existing AMPs across the entire drug development pipeline, significantly accelerating AMP discovery compared to traditional methods.","whyItMatters":"Antimicrobial resistance kills over 1.2 million people annually and that number is rising. Traditional antibiotic discovery is slow and expensive. ML can screen millions of potential peptide sequences in hours rather than years, dramatically accelerating the search for new antimicrobials when we need them most urgently.","specificNumbers":"AI/ML approaches applied across the AMP development pipeline — from identification to design to optimization.","methodology":"Comprehensive review article published in Nature Reviews Bioengineering surveying ML and AI approaches applied to antimicrobial peptide identification, property prediction, structure prediction, and de novo design.","limitations":"Review article — does not present new experimental data. Many ML-designed AMPs remain computationally predicted without experimental validation. ML models are only as good as their training data, which may have biases. Clinical translation involves challenges beyond computational design, including manufacturing, formulation, and regulatory hurdles."},{"rthcId":"RPEP-09465","title":"Effect of survodutide, a glucagon and GLP-1 receptor dual agonist, on weight loss: a meta-analysis of randomized controlled trials.","authors":"Wan, Haijun; Xu, Nuo; Wang, Lijuan; Liu, Yaping; Fatahi, Somaye; Sohouli, Mohammad Hassan; Guimarães, Nathalia Sernizon","year":2024,"journal":"Diabetology & metabolic syndrome, 16(1), 264","doi":"10.1186/s13098-024-01501-x","pmid":"39508238","tags":["glp-1-receptor-agonists","glucagon-and-related","obesity-and-weight-management"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Survodutide produced statistically significant reductions in body weight (-8.33 kg), BMI (-4.03 kg/m²), and waist circumference (-6.33 cm) compared to placebo, with greater effects at higher doses and longer durations.","whyItMatters":"Survodutide's dual-agonist approach — combining appetite suppression (GLP-1) with increased energy burning (glucagon) — could offer advantages over single-mechanism drugs like semaglutide. This meta-analysis provides the first pooled evidence confirming its weight-loss efficacy across all available trials.","specificNumbers":"Meta-analysis of all RCTs of injectable survodutide; assessed weight loss outcomes at various doses.","methodology":"Systematic review and meta-analysis of randomized controlled trials identified through database searches up to August 2024. Used random-effects model to compute weighted mean differences with 95% confidence intervals. Included subgroup analysis by dose and duration, plus meta-regression.","limitations":"High heterogeneity (I² = 99.6% for weight) across studies, likely reflecting dose and duration differences. Limited number of available RCTs for this newer drug. Long-term safety data beyond trial durations not established. No head-to-head comparisons with other GLP-1 agonists in this analysis."},{"rthcId":"RPEP-09466","title":"A large-scale study of peptide features defining immunogenicity of cancer neo-epitopes.","authors":"Wan, Yat-Tsai Richie; Koşaloğlu-Yalçın, Zeynep; Peters, Bjoern; Nielsen, Morten","year":2024,"journal":"NAR cancer, 6(1), zcae002","doi":"10.1093/narcan/zcae002","pmid":"38288446","tags":["cancer-related-peptides","immune-system-peptides","vaccine-peptides"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"The ICERFIRE model, integrating MHC binding prediction, mutation scoring, and antigen expression data from the CEDAR database, showed improved and robust performance over existing tools for predicting cancer neo-epitope immunogenicity.","whyItMatters":"Personalized cancer vaccines need to target the right mutated peptides — the ones that will actually trigger an immune response. Most tumor mutations don't produce immunogenic peptides, so accurate prediction saves time and resources and could mean the difference between an effective vaccine and a failed one for each patient.","specificNumbers":"Used CEDAR database of curated cancer epitopes; comprehensive analysis of peptide features relevant for immunogenicity prediction.","methodology":"Large-scale computational analysis using the Cancer Epitope Database and Analysis Resource (CEDAR). Developed an ensemble random forest model (ICERFIRE) incorporating ICORE extraction, BLOSUM mutation scores, and antigen expression levels. Validated through cross-validation and external datasets.","limitations":"Computational study — predictions need experimental validation for each new application. The CEDAR database may have biases toward certain cancer types or HLA alleles that have been more studied. Immune responses involve many factors beyond peptide features alone (T cell repertoire, tumor microenvironment, patient immune status)."},{"rthcId":"RPEP-09467","title":"The novel angiotensin-I-converting enzyme inhibitory peptides from Scomber japonicus muscle protein hydrolysates: QSAR-based screening, molecular docking, kinetic and stability studies.","authors":"Wang, Baobei; Zhang, Hui; Wen, Yuxi; Yuan, Wenwen; Chen, Hongbin; Lin, Luan; Guo, Fengxian; Zheng, Zong-Ping; Zhao, Chao","year":2024,"journal":"Food chemistry, 447, 138873","doi":"10.1016/j.foodchem.2024.138873","pmid":"38452536","tags":["food-derived-peptides","ace-inhibitory-peptides"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"The novel mackerel-derived peptide PLITT inhibits ACE with IC50 of 48.73 μM through mixed competitive/non-competitive mechanisms via hydrogen bonding, and remains stable under food processing conditions.","whyItMatters":"High blood pressure affects nearly half of adults worldwide and is a leading risk factor for heart disease and stroke. Finding stable, food-derived ACE inhibitors means people could potentially lower blood pressure through functional foods or supplements, complementing or even partially replacing pharmaceutical drugs with fewer side effects.","specificNumbers":"Two novel peptides identified: LTPFT and PLITT; QSAR model based on 5z-scale metrics; molecular docking confirmed binding mechanisms.","methodology":"Developed a QSAR model using 5z-scale descriptors to screen mackerel muscle hydrolysates for ACE-inhibitory peptides. Validated top candidates (LTPFT, PLITT) through in silico screening, molecular docking, enzyme kinetics, and stability testing under heat, pH, glucose, NaCl, and metal ion conditions.","limitations":"In vitro and computational study only — no human or animal blood pressure measurements. Whether enough PLITT survives digestion to reach the bloodstream at therapeutic concentrations is unknown. The IC50 of 48.73 μM, while respectable, means significant amounts would need to be consumed for a blood pressure effect."},{"rthcId":"RPEP-09468","title":"Therapeutic potential of ASK1 activators in cancer treatment: Current insights and future directions.","authors":"Wang, Bo; Ma, Ying; Zhang, Yue; Yin, Xunzhe","year":2024,"journal":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 178, 117214","doi":"10.1016/j.biopha.2024.117214","pmid":"39079264","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09469","title":"Discovery of a Double-Stapled Short Peptide as a Long-Acting HIV-1 Inactivator with Potential for Oral Bioavailability.","authors":"Wang, Chao; Zhang, Wenpeng; Xu, Ling; Tu, Jiahuang; Su, Shan; Li, Qing; Zhang, Tao; Zheng, Longbo; Wang, Huan; Zhuang, Xiaomei; Tang, Xuan; Yuan, Yu; Meng, Guangpeng; Lu, Lu; Xiao, Junhai; Wang, Qian; Jiang, Shibo","year":2024,"journal":"Journal of medicinal chemistry, 67(12), 9991-10004","doi":"10.1021/acs.jmedchem.4c00150","pmid":"38888038","tags":["stapled-peptides","antimicrobial-peptides","oral-peptide-delivery","peptide-therapeutics"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"The double-stapled peptide D26 efficiently inhibits HIV-1 infection and directly inactivates cell-free virions, with high protease resistance, extended in vivo half-life, enhanced sanctuary site penetration, and detectable oral bioavailability.","whyItMatters":"HIV can hide in sanctuary sites (brain, testes, gut tissue) where current drugs barely reach, contributing to the inability to cure the infection. A long-acting peptide that penetrates these sites, directly kills free virus, AND can potentially be taken orally would be a game-changer for HIV treatment — addressing multiple unmet needs simultaneously.","specificNumbers":"Double-stapled peptide D26; based on gp41 LLP3 motif; inhibited HIV-1 infection and inactivated cell-free virions.","methodology":"Designed and synthesized a hydrocarbon double-stapled helical peptide based on the HIV-1 gp41 LLP3 motif. Tested for HIV-1 inhibition, direct virion inactivation, proteolytic stability, pharmacokinetics (half-life), tissue distribution (sanctuary site penetration), and oral absorption compared to linear/non-stapled version.","limitations":"Preclinical study — D26 has not been tested in humans. Oral bioavailability is described as 'detectable' not 'high' — it may not be sufficient for therapeutic dosing orally. Manufacturing double-stapled peptides at clinical scale is challenging and expensive. HIV resistance to D26 has not been assessed. Long-term safety of a gp41-derived peptide is unknown."},{"rthcId":"RPEP-09470","title":"Tumor microenvironment-responsive cell-penetrating peptides: Design principle and precision delivery.","authors":"Wang, Chenhui; Wang, Bo; Zhang, Qing; Zhang, Sihe","year":2024,"journal":"Colloids and surfaces. B, Biointerfaces, 242, 114100","doi":"10.1016/j.colsurfb.2024.114100","pmid":"39024717","tags":["cell-penetrating-peptides","drug-delivery-systems","cancer-related-peptides"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Tumor microenvironment-responsive CPP designs address the selectivity limitation through activation mechanisms triggered by tumor-specific conditions including low pH, overexpressed enzymes, hypoxia, elevated GSH, and ROS.","whyItMatters":"CPPs could revolutionize drug delivery by ferrying therapeutics directly into cancer cells, but their lack of selectivity has prevented clinical use. TME-responsive activation solves this by keeping the CPP 'off' in healthy tissue and 'on' only inside tumors — potentially enabling a new generation of targeted cancer treatments with fewer side effects.","specificNumbers":"Multiple TME-responsive strategies reviewed: pH-responsive, enzyme-responsive, hypoxia-responsive, and multi-responsive designs.","methodology":"Comprehensive review article systematically categorizing TME-responsive CPP strategies by activation mechanism, covering single-stimulus, multi-stimulus, targeted, and reversibly activatable designs, plus their nanomedical applications.","limitations":"Review article — most TME-responsive CPPs are still in preclinical development. Tumor microenvironment heterogeneity (differences between and within tumors) may limit consistent activation. Manufacturing complexity increases with responsive design elements. Few head-to-head comparisons exist between different activation strategies."},{"rthcId":"RPEP-09471","title":"Nebulized Inhalation of Peptide-Modified DNA Origami To Alleviate Acute Lung Injury.","authors":"Wang, Haiyan; Jiao, Yunfei; Ma, Shuaijing; Li, Zhuoting; Gong, Jintao; Jiang, Qiao; Shang, Yingxu; Li, Hongling; Li, Jing; Li, Na; Zhao, Robert Chunhua; Ding, Baoquan","year":2024,"journal":"Nano letters, 24(20), 6102-6111","doi":"10.1021/acs.nanolett.4c01222","pmid":"38739578","tags":["cell-penetrating-peptides","drug-delivery-systems","inflammation-and-immunity"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"R9 peptide-modified triangular DNA origami nanostructures, delivered by nebulization, effectively targeted alveolar macrophages, scavenged ROS, promoted M2 polarization, and reduced lung inflammation in an ALI mouse model.","whyItMatters":"Acute lung injury and ARDS have limited treatment options and high mortality rates, as highlighted during COVID-19. A nebulizable therapy that directly targets the lung macrophages driving inflammation — and can scavenge the damaging oxidants — could provide early intervention before irreversible lung damage occurs.","specificNumbers":"R9 peptide-modified triangular DNA origami (tDONs-R9); nebulized delivery to deep lung; targeted alveolar macrophages.","methodology":"Designed and synthesized tDONs-R9 using DNA origami technology with R9 CPP modification. Tested macrophage uptake and polarization in vitro, then evaluated therapeutic efficacy via nebulized inhalation in an LPS-induced ALI mouse model. Measured ROS levels, cytokine expression, and neutrophil infiltration.","limitations":"Mouse study using LPS-induced ALI — this model doesn't perfectly replicate human ALI/ARDS. Manufacturing DNA origami at clinical scale remains a significant challenge. Long-term safety of DNA nanostructures accumulating in lung tissue is unknown. Only one disease model and one time point were tested."},{"rthcId":"RPEP-09472","title":"ToxTeller: Predicting Peptide Toxicity Using Four Different Machine Learning Approaches.","authors":"Wang, Jen-Hung; Sung, Ting-Yi","year":2024,"journal":"ACS omega, 9(29), 32116-32123","doi":"10.1021/acsomega.4c04246","pmid":"39072096","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09473","title":"Role of neuropeptides in orofacial pain: A literature review.","authors":"Wang, Jian; Liu, Xiangtao; Gou, Junzhuo; Deng, Jing; Li, Mujia; Zhu, Yafen; Wu, Zhifang","year":2024,"journal":"Journal of oral rehabilitation, 51(5), 898-908","doi":"10.1111/joor.13656","pmid":"38213060","tags":["cgrp","neuropeptides","substance-p-and-tachykinins","pain-management"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Neuropeptides in the trigeminal system play distinct roles: CGRP, substance P, NPY, NKA, HK-1, and VIP are pro-inflammatory and pro-nociceptive, while opioid peptides, galanin, oxytocin, and orexin-A are analgesic — identifying multiple therapeutic targets for orofacial pain.","whyItMatters":"Orofacial pain conditions (TMJ disorders, trigeminal neuralgia, dental pain) affect millions and are often poorly managed by existing treatments. Understanding which neuropeptides drive versus inhibit this pain opens doors to targeted therapies — notably, CGRP-blocking drugs have already revolutionized migraine treatment and may extend to orofacial pain.","specificNumbers":"Multiple neuropeptides reviewed including CGRP, substance P, and others involved in trigeminal pain signaling.","methodology":"Systematic literature review summarizing current research on neuropeptide functions and mechanisms in orofacial pain, covering CGRP, substance P, opioid peptides, galanin, and other neuropeptides in the trigeminal sensory system.","limitations":"Review article — synthesizes existing research rather than presenting new data. Many neuropeptide-targeting drugs for orofacial pain remain in preclinical stages. The interplay between multiple neuropeptides in vivo is more complex than studying individual peptides suggests. Clinical translation from trigeminal system research to effective therapies has historically been challenging."},{"rthcId":"RPEP-09474","title":"Impact of Lactiplantibacillus plantarum and casein fortification on angiotensin converting enzyme inhibitory peptides in yogurt: identification and in silico analysis.","authors":"Wang, Jiaxu; Wang, Zhimin; Zhang, Mixia; Li, Jiaxin; Zhao, Cuisong; Ma, Chunli; Ma, Dexing","year":2024,"journal":"Food & function, 15(7), 3824-3837","doi":"10.1039/d3fo04534j","pmid":"38511617","tags":["food-derived-peptides","ace-inhibitory-peptides"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Combining Lb. plantarum M11 with sodium caseinate fortification significantly enhanced ACE-inhibitory peptide production in yogurt, with two identified peptides confirmed by molecular docking to bind ACE's active site.","whyItMatters":"High blood pressure affects nearly half of adults globally. If everyday foods like yogurt can be optimized to deliver clinically meaningful amounts of ACE-blocking peptides, millions of people could supplement their blood pressure management through diet — potentially reducing medication needs.","specificNumbers":"ACE-inhibitory activity significantly enhanced (p < 0.05); molecular docking binding energies of -10.7 kcal/mol or better confirmed for identified peptides.","methodology":"Yogurt was prepared with standard cultures plus Lb. plantarum M11 and sodium caseinate. ACE-inhibitory activity was measured, peptides identified by nano-LC-MS/MS, and potential ACE-inhibitory peptides predicted using in silico analysis and molecular docking to ACE crystal structure.","limitations":"In vitro ACE inhibition and computational modeling only — no human blood pressure measurements. Whether sufficient ACE-blocking peptides survive digestion and reach the bloodstream is unknown. The yogurt was not tested in clinical trials. Binding energies from docking are predictions, not measurements."},{"rthcId":"RPEP-09475","title":"Enhanced Gut-to-Liver Oral Drug Delivery via Ligand-Modified Nanoparticles by Attenuating Protein Corona Adsorption.","authors":"Wang, Jie; Zhang, Zilong; Zhang, Zhuan; Zou, Zhiwen; Zhuo, Yan; Liu, Chang; Nie, Di; Gan, Yong; Yu, Miaorong","year":2024,"journal":"ACS nano, 18(52), 35310-35324","doi":"10.1021/acsnano.4c11453","pmid":"39681528","tags":["drug-delivery-systems","oral-peptide-delivery"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"Small cyclic FcRn-binding peptide-decorated nanoparticles showed superior intestinal transport, reduced protein corona formation, and effective oral delivery of exenatide in diabetic mice compared to larger IgG-decorated nanoparticles.","whyItMatters":"Oral delivery of peptide drugs would eliminate the need for daily injections — a major barrier to patient compliance for diabetes and other chronic diseases. This study demonstrates that the right surface coating (a small peptide vs. a large protein) can make or break oral nanoparticle delivery by controlling protein corona formation.","specificNumbers":"Mesoporous silica nanoparticles (MSNs) with ligand modifications; demonstrated GI survival and liver targeting with reduced protein corona.","methodology":"Functionalized mesoporous silica nanoparticles with either a small cyclic FcRn-binding peptide (MSNs-FcBP) or large IgG Fc fragments (MSNs-Fc). Compared mucus diffusion, intestinal transport, protein corona formation, and liver accumulation. Conducted pharmacokinetic and pharmacodynamic studies in diabetic mice with oral exenatide delivery.","limitations":"Mouse study — human GI tract physiology differs significantly. Long-term safety of silica nanoparticle accumulation in the liver needs assessment. The exenatide dose delivered orally may not match injectable bioavailability. Scale-up of peptide-functionalized nanoparticles for manufacturing is complex."},{"rthcId":"RPEP-09476","title":"Effect of semaglutide on primary prevention of diabetic kidney disease in people with type 2 diabetes: A post hoc analysis of the SUSTAIN 6 randomized controlled trial.","authors":"Wang, Jingyu; Yang, Juhong; Jiang, Wenhui; Liu, Wenyan; Shen, Zewei; Gao, Zhongai; Chang, Baocheng","year":2024,"journal":"Diabetes, obesity & metabolism, 26(11), 5157-5166","doi":"10.1111/dom.15860","pmid":"39188242","tags":["glp-1-receptor-agonists","semaglutide","kidney-health","diabetes-and-blood-sugar"],"studyType":"RCT","evidenceStrength":"moderate","keyFinding":"Semaglutide reduced the odds of developing new diabetic kidney disease by 44% overall (OR 0.56, p<0.0001) and 49% in high-risk patients (OR 0.51), with NNT of 7 in the high-risk population, primarily by reducing urinary albumin excretion.","whyItMatters":"Diabetic kidney disease leads to dialysis for millions of people worldwide and is the leading cause of kidney failure. Finding that semaglutide — already widely prescribed for diabetes and weight loss — can nearly halve the risk of developing DKD means a drug many patients are already taking could protect their kidneys too, potentially preventing years of dialysis.","specificNumbers":"SUSTAIN 6 participants classified by DKD risk model; semaglutide vs. placebo for primary DKD prevention.","methodology":"Post hoc analysis of the SUSTAIN 6 randomized, double-blind, placebo-controlled trial. Included 1,139 participants with T2D without DKD at baseline. Stratified by validated DKD risk model. Primary outcome: development of DKD (UACR ≥30 mg/g and/or eGFR decline). Compared semaglutide 0.5/1.0 mg vs. placebo.","limitations":"Post hoc analysis — not a pre-specified trial endpoint, so results need confirmation in prospective studies. The DKD risk model classification may not capture all relevant patient differences. SUSTAIN 6 was not designed or powered to assess DKD prevention specifically. The analysis doesn't distinguish between semaglutide's direct kidney effects and indirect effects through blood sugar and weight reduction."},{"rthcId":"RPEP-09477","title":"Peptide Toxin Diversity and a Novel Antimicrobial Peptide from the Spider Oxyopes forcipiformis.","authors":"Wang, Kexin; Mwangi, James; Cao, Kaixun; Wang, Yi; Gao, Jinai; Yang, Min; Michira, Brenda B; Lu, Qiumin; Li, Juan","year":2024,"journal":"Toxins, 16(11)","doi":"10.3390/toxins16110466","pmid":"39591221","tags":["venom-derived-peptides","antimicrobial-peptides"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"A novel antimicrobial peptide GK37 from lynx spider venom showed potent antibacterial activity against S. aureus (MIC: 1.552 μM) through membrane disruption, with negligible hemolytic activity and cytotoxicity at 4× MIC concentrations.","whyItMatters":"Antibiotic-resistant Staphylococcus aureus (MRSA) is a critical public health threat. Spider venom peptides evolved over millions of years to kill microorganisms, offering a vast untapped library of potential new antibiotics. GK37's combination of potent antibacterial activity with low human toxicity makes it a promising drug lead.","specificNumbers":"339 putative protein and peptide toxin sequences identified; categorized into multiple toxin families; novel antimicrobial peptide discovered.","methodology":"Transcriptome analysis of venom glands from Oxyopes forcipiformis. Peptide sequences categorized by function and analyzed phylogenetically. GK37 identified through in silico and homology analysis, then tested for antimicrobial activity (MIC assay), mechanism of action (membrane disruption), hemolytic activity, and cytotoxicity against HEK293T cells.","limitations":"Only tested against one bacterial species (S. aureus) — broader spectrum activity unknown. In vitro study only — no animal infection models. Manufacturing spider venom peptides at scale is expensive. Stability in biological fluids and pharmacokinetics not assessed. Only one of 339 identified peptides was functionally characterized."},{"rthcId":"RPEP-09478","title":"Synthesis and Evaluation of 68Ga- and 177Lu-Labeled [Pro14]bombesin(8-14) Derivatives for Detection and Radioligand Therapy of Gastrin-Releasing Peptide Receptor-Expressing Cancer.","authors":"Wang, Lei; Kuo, Hsiou-Ting; Chapple, Devon E; Chen, Chao-Cheng; Kurkowska, Sara; Colpo, Nadine; Uribe, Carlos; Bénard, François; Lin, Kuo-Shyan","year":2024,"journal":"Molecular pharmaceutics, 21(12), 6385-6397","doi":"10.1021/acs.molpharmaceut.4c00952","pmid":"39460729","tags":["radiolabeled-peptides","cancer-related-peptides","bombesin-and-grp"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"The bombesin peptide modification Thz14→Pro14 produced [68Ga]Ga-ProBOMB5 with high tumor uptake (12.4±1.35%ID/g), strong binding affinity (Ki: 12.2 nM), and minimal pancreas accumulation (0.60-1.37%ID/g) — a major improvement over existing GRPR tracers.","whyItMatters":"GRPR-targeted imaging could transform prostate cancer diagnosis and treatment monitoring, but high pancreas radiation has been a deal-breaker for most tracers. ProBOMB5's minimal pancreas uptake removes this barrier, potentially enabling safe, routine use of GRPR PET imaging to detect and monitor cancers that express this receptor.","specificNumbers":"One antagonist (ProBOMB5) and two agonists (LW02056, LW02057) synthesized; labeled with 68Ga and 177Lu; Pro14 substitution replacing Thz14 residue.","methodology":"Synthesized three [Pro14]bombesin(8-14) derivatives (one antagonist, two agonists). Performed 68Ga and 177Lu radiolabeling, in vitro binding affinity assays (Ki), PET imaging and biodistribution in PC-3 tumor-bearing mice at 1h post-injection, and longitudinal SPECT imaging comparing [177Lu]Lu-ProBOMB5 with [177Lu]Lu-RM2.","limitations":"Mouse study — human biodistribution may differ. The therapeutic lutetium-177 version showed faster tumor clearance than RM2, limiting its radiation dose to tumors for therapy. Only one tumor model (PC-3) tested. Clinical trials needed to confirm the favorable pancreas profile in humans."},{"rthcId":"RPEP-09479","title":"Collagen peptides from sturgeon swim bladder prolong the lifespan and healthspan in Caenorhabditis elegans.","authors":"Wang, Lin; Li, Peiyu; Zheng, Fuping; Zhu, Zhiling; Bai, Fan; Gao, Ruichang","year":2024,"journal":"Journal of the science of food and agriculture, 104(9), 5244-5251","doi":"10.1002/jsfa.13348","pmid":"38308527","tags":["collagen-peptides","food-derived-peptides","longevity-and-aging"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Sturgeon swim bladder collagen peptides extended C. elegans lifespan by 22.6% and improved multiple healthspan indicators, mediated through MAPK, insulin/IGF-1, and NHR-80/FAT-6 lipid metabolism pathways.","whyItMatters":"The anti-aging supplement market is enormous but largely unsupported by evidence. This study provides mechanistic data showing specific collagen peptides activate three established longevity pathways simultaneously. While worm results don't directly translate to humans, the identified pathways (insulin/IGF-1, MAPK, lipid metabolism) are conserved across species and are key targets in aging research.","specificNumbers":"Average molecular weight 528.5 Da; 407 peptides identified; 16.1% was GFPGADGSAGPK; 22.6% lifespan extension at 25 mg/mL.","methodology":"Collagen peptides prepared by trypsinolysis of sturgeon swim bladder. Characterized by molecular weight and peptide composition (nano-LC-MS/MS). Tested in C. elegans for lifespan, body size, motor capacity, oxidative stress resistance, cell apoptosis, and epidermal barrier function. Transcriptome analysis to identify pathway mechanisms.","limitations":"C. elegans is a simple worm model — results may not translate to mammals or humans. No dose-response relationship in mammals established. The 22.6% lifespan extension at a specific concentration may not scale linearly. Individual peptide contributions vs. synergistic effects are unclear. Human bioavailability of these collagen peptides after oral consumption is unknown."},{"rthcId":"RPEP-09480","title":"Liraglutide reduces bone marrow adipogenesis by miR-150-5p/ GDF11 axis in diabetic rats.","authors":"Wang, Na; Lin, Zhe; Gao, Liu; Wang, Bin; Wei, Kangxu; Zhang, Menghan; Li, Yukun; Xue, Peng","year":2024,"journal":"European journal of pharmacology, 978, 176793","doi":"10.1016/j.ejphar.2024.176793","pmid":"38960061","tags":["glp-1-receptor-agonists","liraglutide","bone-and-joint-health"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Liraglutide reduces bone marrow fat accumulation in diabetic rats by suppressing miR-150-5p expression, which upregulates GDF11 — a novel mechanism explaining the peptide drug's bone-protective effects.","whyItMatters":"Diabetes significantly increases fracture risk, partly through excess bone marrow fat replacing healthy bone-forming tissue. Discovering that liraglutide — already widely prescribed for diabetes — protects bone marrow through a specific molecular pathway adds another reason to consider GLP-1 agonists for diabetic patients at risk of bone disease.","specificNumbers":"HFD + STZ diabetic rat model; liraglutide treatment; miR-150-5p and GDF11 identified as key pathway mediators.","methodology":"Diabetic rat model (HFD + STZ). High-throughput miRNA sequencing of BMSCs after liraglutide treatment identified differentially expressed miRNAs. Validated miR-150-5p/GDF11 axis using overexpression/knockdown studies in vitro (high-glucose BMSCs) and agomiR injection in vivo. Assessed bone marrow lipid accumulation histologically.","limitations":"Animal study — human bone marrow response may differ. The HFD+STZ rat model is a simplified version of human type 2 diabetes. Only miR-150-5p was deeply characterized among the five changed miRNAs — the others may contribute. The study focused on adipogenesis but didn't assess bone density or fracture outcomes. Liraglutide dosing in rats may not correspond to human doses."},{"rthcId":"RPEP-09481","title":"Proteomic Barcoding Platform for Macromolecular Screening and Delivery.","authors":"Wang, Ning; Mcneer, Nicole A; Eton, Elliot; Fass, Josh; Kentsis, Alex","year":2024,"journal":"Journal of proteome research, 23(6), 2067-2077","doi":"10.1021/acs.jproteome.4c00068","pmid":"38776430","tags":["peptide-engineering","drug-delivery-systems"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"The BarcodeBabel/PeptideBabel platform enabled high-throughput screening of CPP libraries via mass spectrometry barcoding, identifying cell-penetrating peptides that delivered hundreds of millions of molecules per cell with minimal toxicity.","whyItMatters":"Drug delivery is the biggest bottleneck for therapeutic peptides and proteins. Traditional CPP screening is slow (one peptide at a time), but this barcoding approach screens entire libraries simultaneously. By dramatically accelerating CPP discovery, it could speed the development of intracellular delivery solutions for biologics, gene therapies, and other macromolecular drugs.","specificNumbers":"BarcodeBabel generates libraries of unique peptide barcodes; PeptideBabel uses Monte Carlo sampling for design optimization.","methodology":"Developed BarcodeBabel for designing mass-spectrometry-compatible peptide barcode libraries. Created PeptideBabel using Monte Carlo sampling for CPP design with varied physicochemical properties. Screened barcoded CPP libraries using quantitative targeted mass spectrometry. Measured nuclear and cytoplasmic delivery, membrane disruption, and cytotoxicity in vitro.","limitations":"In vitro proof-of-concept — top CPPs haven't been validated in vivo. Mass spectrometry-based readout requires specialized equipment. The barcoding approach measures total peptide delivered but doesn't distinguish between different intracellular compartments beyond nucleus vs. cytoplasm. Library diversity is constrained by barcode design rules."},{"rthcId":"RPEP-09482","title":"Bitter-tasting drugs tune GDF15 and GLP-1 expression via bitter taste or motilin receptors in the intestine of patients with obesity.","authors":"Wang, Qian; Farhadipour, Mona; Thijs, Theo; Ruilova Sosoranga, Emily; Van der Schueren, Bart; Ceulemans, Laurens J; Deleus, Ellen; Lannoo, Matthias; Tack, Jan; Depoortere, Inge","year":2024,"journal":"Molecular metabolism, 88, 102002","doi":"10.1016/j.molmet.2024.102002","pmid":"39111389","tags":["glp-1-receptor-agonists","gut-health-peptides","obesity-and-weight-management"],"studyType":"in vitro","evidenceStrength":"moderate","keyFinding":"Bitter compounds regulate GDF15 and GLP-1 release from human gut epithelial cells through specific TAS2R subtypes and the unfolded protein response, with TAS2R polymorphisms predicting therapeutic responsiveness.","whyItMatters":"This reveals a completely new mechanism for controlling appetite — bitter taste receptors in the gut that regulate two powerful satiety signals simultaneously. Since genetic variations predict who responds, this could enable personalized obesity treatment based on taste receptor genetics, offering an alternative to injectable GLP-1 drugs.","specificNumbers":"GDF15 acts via GFRAL receptor in hindbrain; 25 TAS2R subtypes exist in gut; both TAS2Rs and motilin receptors mediate bitter compound effects.","methodology":"Placebo-controlled, double-blind, randomized crossover study of oral hydroxychloroquine in healthy volunteers (plasma GDF15, ghrelin, hunger scores). Ex vivo stimulation of primary jejunal crypts from patients with obesity. Immunofluorescence colocalization. TAS2R antagonist (GIV3727) blocking studies. TAS2R4/43 genotyping for polymorphism analysis.","limitations":"Small crossover study in healthy volunteers — larger obesity trials needed. Ex vivo gut tissue experiments may not fully reflect in vivo responses. The bitter compounds tested have other pharmacological effects beyond taste receptors. Not all bitter compounds had the same direction of effect on GDF15. Long-term efficacy and tolerability of bitter-based appetite suppression unknown."},{"rthcId":"RPEP-09483","title":"Nociceptor mechanisms underlying pain and bone remodeling via orthodontic forces: toward no pain, big gain.","authors":"Wang, Sheng; Ko, Ching-Chang; Chung, Man-Kyo","year":2024,"journal":"Frontiers in pain research (Lausanne, Switzerland), 5, 1365194","doi":"10.3389/fpain.2024.1365194","pmid":"38455874","tags":["cgrp","substance-p-and-tachykinins","neuropeptides","bone-and-joint-health","pain-management"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"TRPV1-expressing periodontal nociceptors release neuropeptides (CGRP, substance P) that mediate orthodontic pain and may also regulate alveolar bone remodeling during tooth movement, creating a dual neuroskeletal interaction.","whyItMatters":"Orthodontic pain affects millions of patients and is the leading cause of treatment discontinuation. Understanding that neuropeptides both cause the pain and influence tooth movement means we could develop targeted therapies that reduce pain while preserving — or even accelerating — the desired tooth movement.","specificNumbers":"Neuropeptides including CGRP and substance P identified as dual mediators of orthodontic pain and bone remodeling.","methodology":"Review article synthesizing research on nociceptor mechanisms in orthodontic pain, covering molecular transducers (TRPV1, TRPA1, ASIC3, P2X3), neuropeptide signaling (CGRP, substance P), and the potential neuroskeletal interactions between pain-sensing nerves and bone remodeling.","limitations":"Review article — most evidence comes from animal models. The relationship between nociceptors and bone remodeling in orthodontics is hypothesized but not yet proven in clinical settings. Blocking neuropeptides to reduce pain could potentially slow tooth movement if the neuroskeletal coupling is confirmed. Individual pain sensitivity varies widely."},{"rthcId":"RPEP-09484","title":"Angiotensin converting enzyme (ACE) inhibitory peptide from the tuna (Thunnus thynnus) muscle: Screening, interaction mechanism and stability.","authors":"Wang, Shu; Zhang, Lu; Wang, Hui; Liu, Jiaojiao; Hu, Yueming; Tu, Zongcai","year":2024,"journal":"International journal of biological macromolecules, 279(Pt 4), 135469","doi":"10.1016/j.ijbiomac.2024.135469","pmid":"39250996","tags":["food-derived-peptides","ace-inhibitory-peptides"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"The novel tuna muscle peptide LTGCP inhibits ACE (IC50: 64.3 μM) through mixed-type inhibition, forming a stable 7-hydrogen-bond complex, and retains activity after gastrointestinal digestion with no intestinal cell toxicity.","whyItMatters":"Finding ACE inhibitors that survive digestion is the critical bottleneck for food-derived blood pressure peptides. LTGCP's demonstrated stability through simulated gastrointestinal conditions, combined with its non-toxicity, makes it one of the more practically viable food-derived ACE inhibitors reported — a genuine candidate for nutraceutical development.","specificNumbers":"5 novel ACE-I peptides identified; two-step enzymatic hydrolysis; multiple purification steps; Q-Orbitrap-MS/MS identification.","methodology":"Two-step enzymatic hydrolysis (Neutrase + Alkaline) of tuna muscle. Purification by ultrafiltration, gel chromatography, and RP-HPLC. Peptide identification by Q-Orbitrap-MS/MS. ACE inhibition kinetics, molecular docking, molecular dynamics simulation. Stability testing under heat, pH, and simulated GI digestion. Caco-2 cytotoxicity assay.","limitations":"In vitro study only — no animal or human blood pressure measurements. Simulated GI digestion doesn't perfectly replicate in vivo conditions. Whether LTGCP is actually absorbed across the intestinal wall (bioavailability) wasn't tested. The IC50 of 64.3 μM, while respectable, means substantial amounts would need to be consumed. Molecular dynamics simulations are computational predictions."},{"rthcId":"RPEP-09485","title":"Identification of novel angiotensin converting enzyme (ACE) inhibitory peptides from Pacific saury: In vivo antihypertensive effect and transport route.","authors":"Wang, Shu; Zhang, Lu; Wang, Hui; Hu, Zizi; Xie, Xing; Chen, Haiqi; Tu, Zongcai","year":2024,"journal":"International journal of biological macromolecules, 254(Pt 1), 127196","doi":"10.1016/j.ijbiomac.2023.127196","pmid":"37793525","tags":["food-derived-peptides","ace-inhibitory-peptides","oral-peptide-delivery"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"The Pacific saury peptide LEPWR inhibits ACE (IC50: 99.5 μM) through mixed competitive inhibition with 6 hydrogen bonds, and demonstrates intestinal absorption via paracellular transport (Papp: 3.56×10⁻⁶ cm/s) through Caco-2 monolayers.","whyItMatters":"This study goes beyond most food peptide research by demonstrating both in vivo blood pressure reduction AND intestinal absorption — the two critical requirements for a food-derived peptide to actually work as an oral antihypertensive. The paracellular transport route provides a mechanistic explanation for how small peptides from food can reach the bloodstream.","specificNumbers":"Novel peptide sequences identified; antihypertensive effect confirmed in SHR model; transport routes characterized.","methodology":"Bioactivity-guided purification of Pacific saury hydrolysates via ultrafiltration, Sephadex G-25, and RP-HPLC. Antihypertensive effect confirmed in SHR model. Peptide identification by Q-Orbitrap-MS/MS. Molecular docking for binding analysis. Caco-2 monolayer transport studies with apparent permeability measurement and transport route characterization.","limitations":"The SHR blood pressure reduction was shown for the crude hydrolysate fraction, not purified LEPWR specifically. The IC50 of 99.5 μM is moderate — higher doses would be needed. Caco-2 monolayers are a model, not real intestine. Long-term antihypertensive effect and dose-response relationship in animals not established. Papp of 3.56×10⁻⁶ cm/s indicates moderate absorption, not high."},{"rthcId":"RPEP-09486","title":"Substance P regulates memory Th17 cell generation and maintenance in chronic dry eye disease.","authors":"Wang, Shudan; Naderi, Amirreza; Kahale, Francesca; Ortiz, Gustavo; Forouzanfar, Katayoon; Chen, Yihe; Dana, Reza","year":2024,"journal":"Journal of leukocyte biology, 116(6), 1446-1453","doi":"10.1093/jleuko/qiae142","pmid":"38916986","tags":["substance-p-and-tachykinins","neuropeptides","immune-system-peptides","autoimmune-conditions"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"Substance P promotes memory Th17 cell generation and maintenance in chronic dry eye disease via NK1R, and in vivo NK1R antagonist treatment disrupts both memory Th17 formation and persistence.","whyItMatters":"Chronic dry eye affects over 300 million people worldwide and current treatments (artificial tears, anti-inflammatory drops) don't address the underlying memory immune cells that sustain the disease. Targeting substance P/NK1R could break the cycle of chronic inflammation at its source by eliminating the memory immune cells that keep dry eye going indefinitely.","specificNumbers":"Substance P acts via neurokinin 1 receptor; drives memory Th17 cell generation and maintenance in chronic dry eye.","methodology":"In vitro culture of effector and memory T cells from acute and chronic dry eye mouse models with substance P and NK1R antagonist. In vivo NK1R antagonist treatment during resolution phase (memory generation) and chronic phase (memory maintenance) of dry eye disease. Assessed memory Th17 cell populations by flow cytometry.","limitations":"Mouse model — human dry eye may involve additional mechanisms. The NK1R antagonist was applied as research tool, not as an optimized therapeutic formulation. Long-term effects of NK1R blockade on ocular surface immunity (including protective immunity) not assessed. Unclear if substance P is the only neuropeptide maintaining memory Th17 cells."},{"rthcId":"RPEP-09487","title":"A novel intranasal peptide vaccine inhibits non-small cell lung cancer with KRAS mutation.","authors":"Wang, Su He; Cao, Zhengyi; Farazuddin, Mohammad; Chen, Jesse; Janczak, Katarzyna W; Tang, Shengzhuang; Cannon, Jayme; Baker, James R","year":2024,"journal":"Cancer gene therapy, 31(3), 464-471","doi":"10.1038/s41417-023-00717-9","pmid":"38177307","tags":["cancer-related-peptides","vaccine-peptides","immune-system-peptides"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Intranasal KRAS peptide vaccine with nanoemulsion adjuvant significantly reduced lung tumor incidence in KRAS-mutant mice by inducing persistent KRAS-specific Th1/Th17 responses and reducing immunosuppressive regulatory T cells.","whyItMatters":"KRAS mutations account for about 25% of all lung cancers and have been notoriously difficult to target therapeutically. An intranasal peptide vaccine could prevent KRAS-driven tumors from developing or catch them early — particularly valuable for high-risk individuals like former heavy smokers with known KRAS mutations.","specificNumbers":"Vaccine used mutated and wild-type KRAS peptides; intranasal delivery; tested in NSCLC animal models.","methodology":"Intranasal immunization of mice with mutated and wild-type KRAS peptides in nanoemulsion adjuvant. Used inducible mutant KRAS lung tumor mouse model. Assessed immune responses (CD4/CD8 T cells, cytokines, FoxP3+ Tregs) and tumor incidence. Persistence evaluated at 3 months post-vaccination.","limitations":"Mouse study — human immune responses to KRAS peptides may differ. The inducible KRAS model is artificial compared to natural tumor development. Immune response persistence beyond 3 months not assessed. The vaccine's effectiveness against established tumors (therapeutic use) was not tested. Optimal dose, schedule, and adjuvant for humans are unknown."},{"rthcId":"RPEP-09488","title":"Targeting IGF1/IGF1r signaling relieve pain and autophagic dysfunction in NTG-induced chronic migraine model of mice.","authors":"Wang, Tianxiao; Zhu, Chenlu; Zhang, Kaibo; Gao, Jinggui; Xu, Yunhao; Duan, Chenyang; Wu, Shouyi; Peng, Cheng; Guan, Jisong; Wang, Yonggang","year":2024,"journal":"The journal of headache and pain, 25(1), 156","doi":"10.1186/s10194-024-01864-6","pmid":"39304806","tags":["igf-1","neuropeptides","pain-management"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"IGF1r antagonist picropodophyllin alleviated chronic migraine-related pain behaviors and reduced CGRP and c-Fos expression in the trigeminal nucleus caudalis, identifying IGF1/IGF1r signaling as a contributor to chronic migraine.","whyItMatters":"Despite anti-CGRP drugs improving migraine treatment, many patients don't respond adequately. IGF1/IGF1r represents an upstream pathway that drives CGRP expression and neuronal sensitization. Targeting this pathway could help patients who don't respond to CGRP-based therapies, offering a complementary or alternative approach to chronic migraine prevention.","specificNumbers":"NTG-induced chronic migraine model; IGF1/IGF1r pathway targeted; pain relief and autophagy restoration demonstrated.","methodology":"Chronic migraine induced in mice by repeated nitroglycerin (NTG) injections. Assessed mechanical and thermal sensitivity. Treated with IGF1r antagonist PPP. Measured IGF1, phospho-IGF1r, CGRP, c-Fos expression, and autophagy markers in the TNC by immunostaining and Western blot.","limitations":"Mouse model using nitroglycerin injections — an imperfect model of human chronic migraine. PPP is a research tool compound, not an approved drug. The specific mechanism linking IGF1r signaling to CGRP upregulation wasn't fully delineated. Only mechanical and thermal sensitivity were assessed — migraine involves many other symptoms. No human data."},{"rthcId":"RPEP-09489","title":"Attenuating mitochondrial dysfunction and morphological disruption with PT320 delays dopamine degeneration in MitoPark mice.","authors":"Wang, Vicki; Tseng, Kuan-Yin; Kuo, Tung-Tai; Huang, Eagle Yi-Kung; Lan, Kuo-Lun; Chen, Zi-Rong; Ma, Kuo-Hsing; Greig, Nigel H; Jung, Jin; Choi, Ho-Ii; Olson, Lars; Hoffer, Barry J; Chen, Yuan-Hao","year":2024,"journal":"Journal of biomedical science, 31(1), 38","doi":"10.1186/s12929-024-01025-6","pmid":"38627765","tags":["glp-1-receptor-agonists","exenatide","brain-and-cognition"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"PT320 (sustained-release exenatide) preserved mitochondrial function and morphology in PD model mice by reducing Fis1 and increasing Opa1, lowering ROS and preventing cytochrome c release during dopamine neuron degeneration.","whyItMatters":"Exenatide has shown promise in human PD clinical trials, but the mechanism wasn't understood. This study reveals it protects dopamine neurons by keeping their mitochondria healthy — specifically by balancing the proteins that control mitochondrial shape and function. This mechanistic understanding could guide clinical trial design and patient selection.","specificNumbers":"PT320 (sustained-release exenatide); MitoPark mouse model; mitochondrial dysfunction and morphology assessed; dopamine neuron degeneration delayed.","methodology":"Clinically translatable dose of PT320 administered to MitoPark mice (progressive PD model with dopamine neuron-specific mitochondrial dysfunction). Assessed tyrosine hydroxylase expression, ROS levels, cytochrome c release, mitochondrial morphology, and genetic analysis of mitochondrial dynamics proteins (Fis1, Opa1).","limitations":"MitoPark mice have an artificial mitochondrial defect that doesn't perfectly replicate human PD. The treatment preserved mitochondrial quality but couldn't prevent declining mitochondrial numbers. PT320 was given early — whether it helps in later-stage disease is unknown. A single dose level was tested. Human PD involves additional pathways beyond mitochondrial dysfunction."},{"rthcId":"RPEP-09490","title":"Efficacy and safety of oral semaglutide monotherapy vs placebo in a predominantly Chinese population with type 2 diabetes (PIONEER 11): a double-blind, Phase IIIa, randomised trial.","authors":"Wang, Weiqing; Bain, Stephen C; Bian, Fang; Chen, Rui; Gabery, Sanaz; Huang, Shan; Jensen, Thomas B; Luo, Bifen; Yuan, Guoyue; Ning, Guang","year":2024,"journal":"Diabetologia, 67(9), 1783-1799","doi":"10.1007/s00125-024-06142-3","pmid":"38985162","tags":["glp-1-receptor-agonists","semaglutide","oral-peptide-delivery","diabetes-and-blood-sugar"],"studyType":"RCT","evidenceStrength":"strong","keyFinding":"Oral semaglutide significantly reduced HbA1c at all doses (3, 7, 14 mg) and body weight at 7 and 14 mg vs. placebo in predominantly Chinese T2D patients, with safety consistent with global PIONEER trials.","whyItMatters":"Oral semaglutide eliminates the need for injection — a major advance for patient convenience. PIONEER 11 confirms efficacy in a predominantly Chinese population, where diabetes prevalence is surging. This is important because metabolic responses can vary by ethnicity, and Chinese patients represent a major portion of the global diabetes population.","specificNumbers":"52 trial sites; predominantly Chinese population; participants ≥18 years (≥20 in Taiwan); double-blind placebo-controlled design.","methodology":"Double-blind, randomized, Phase IIIa, placebo-controlled trial (PIONEER 11). 521 participants across 52 sites. 1:1:1:1 randomization to oral semaglutide 3/7/14 mg or placebo for 26 weeks with 4-week dose escalation. Primary endpoint: HbA1c change at week 26. Confirmatory secondary: body weight change.","limitations":"26-week study — longer-term efficacy and safety data from this population needed. Monotherapy only — most T2D patients use combination therapy. No comparison with other oral diabetes drugs or injectable semaglutide. Gastrointestinal side effects were more common with semaglutide. Chinese subpopulation had slightly higher adverse event rates."},{"rthcId":"RPEP-09491","title":"Functional Peptides from Yak Milk Casein: Biological Activities and Structural Characteristics.","authors":"Wang, Wen; Liang, Qi; Zhao, Baotang; Chen, Xuhui; Song, Xuemei","year":2024,"journal":"International journal of molecular sciences, 25(16)","doi":"10.3390/ijms25169072","pmid":"39201758","tags":["food-derived-peptides","antimicrobial-peptides","ace-inhibitory-peptides","antioxidant-peptides"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Yak milk casein degradation peptides exhibit ACE-inhibitory, antioxidant, anti-inflammatory, antidiabetic, antimicrobial, anticancer, and immunomodulatory activities, with bioactivity closely linked to peptide structural characteristics.","whyItMatters":"Yak milk is produced by over 16 million yaks across the Tibetan plateau and surrounding highlands, but its bioactive potential is underexploited. With casein content higher than cow's milk and a unique protein composition from high-altitude adaptation, yak milk peptides could offer distinct health benefits not available from conventional dairy sources.","specificNumbers":"Yak milk casein: 40.2 g/L average; multiple bioactive activities documented; studied using proteomics, bioinformatics, and in vitro/cellular methods.","methodology":"Comprehensive review of published research on yak milk casein degradation peptides, covering in vitro activity assays, cellular experiments, proteomics, and bioinformatics analyses. Systematic classification of structure-activity relationships by peptide features.","limitations":"Review article — synthesizes existing research without new data. Most studies are in vitro — human health effects of yak milk casein peptides are largely unproven. Bioavailability after oral consumption is uncertain. Yak milk availability is geographically limited. Whether yak casein peptides offer advantages over cow milk casein peptides for most applications is unclear."},{"rthcId":"RPEP-09492","title":"Association of Semaglutide With Tobacco Use Disorder in Patients With Type 2 Diabetes : Target Trial Emulation Using Real-World Data.","authors":"Wang, William; Volkow, Nora D; Berger, Nathan A; Davis, Pamela B; Kaelber, David C; Xu, Rong","year":2024,"journal":"Annals of internal medicine, 177(8), 1016-1027","doi":"10.7326/M23-2718","pmid":"39074369","tags":["glp-1-receptor-agonists","semaglutide","brain-and-cognition","mental-health-peptides"],"studyType":"cohort","evidenceStrength":"strong","keyFinding":"Semaglutide was associated with significantly lower tobacco use disorder-related healthcare encounters (HR 0.68-0.88), cessation medication prescriptions, and cessation counseling compared to seven other diabetes drugs, with effects emerging within 30 days.","whyItMatters":"Tobacco use kills over 8 million people annually, and existing cessation aids have limited effectiveness. If semaglutide reduces smoking behavior, it could provide a completely new pharmacological approach to tobacco addiction — particularly valuable since many smokers have comorbid diabetes and obesity, conditions semaglutide already treats.","specificNumbers":"Nationwide US EHR database; patients with comorbid T2DM and tobacco use disorder; semaglutide vs. other diabetes drugs.","methodology":"Target trial emulation using nationwide US electronic health records. Compared 5,967 new semaglutide users vs. users of 7 other antidiabetes medications (222,942 total) among patients with comorbid T2D and TUD. Outcomes: TUD-related medical encounters, cessation medication prescriptions, and cessation counseling over 12 months. Cox proportional hazards and Kaplan-Meier analyses.","limitations":"Observational study — cannot prove causation. Key limitation: lower TUD-related encounters could reflect reduced care-seeking rather than reduced smoking. No data on actual cigarette consumption or smoking status. Semaglutide users may differ systematically from comparator groups. Only T2D patients with documented TUD studied. Medication adherence not verified."},{"rthcId":"RPEP-09493","title":"Associations of semaglutide with incidence and recurrence of alcohol use disorder in real-world population.","authors":"Wang, William; Volkow, Nora D; Berger, Nathan A; Davis, Pamela B; Kaelber, David C; Xu, Rong","year":2024,"journal":"Nature communications, 15(1), 4548","doi":"10.1038/s41467-024-48780-6","pmid":"38806481","tags":["glp-1-receptor-agonists","semaglutide","brain-and-cognition","mental-health-peptides"],"studyType":"cohort","evidenceStrength":"strong","keyFinding":"Semaglutide was associated with 50-56% lower risk for both incidence and recurrence of alcohol use disorder compared to other anti-obesity medications, consistent across demographic subgroups and replicated in a T2D cohort.","whyItMatters":"Alcohol use disorder is a top-10 global cause of disease burden with limited effective treatments. If semaglutide genuinely reduces alcohol use, it could fill an enormous therapeutic gap — especially since it's already widely prescribed for diabetes and obesity, meaning the safety profile is well-established and access infrastructure exists.","specificNumbers":"83,825 patients with obesity; 50-56% lower risk for both incidence and recurrence of alcohol use disorders; compared to other anti-obesity medications.","methodology":"Retrospective cohort study using electronic health records. Primary cohort: 83,825 obesity patients. Replication cohort: 598,803 T2D patients. Compared semaglutide vs. other anti-obesity medications. Outcomes: AUD incidence and recurrence over 12-month follow-up. Stratified by gender, age, race, and diabetes status.","limitations":"Retrospective observational study — cannot prove causation. Potential confounders include differences in health-seeking behavior between semaglutide and comparator users. AUD diagnosis depends on clinical recognition, which may be inconsistent. No data on actual alcohol consumption amounts. Medication adherence not assessed. Self-reported desire to drink was not measured."},{"rthcId":"RPEP-09494","title":"Associations of semaglutide with first-time diagnosis of Alzheimer's disease in patients with type 2 diabetes: Target trial emulation using nationwide real-world data in the US.","authors":"Wang, William; Wang, QuangQiu; Qi, Xin; Gurney, Mark; Perry, George; Volkow, Nora D; Davis, Pamela B; Kaelber, David C; Xu, Rong","year":2024,"journal":"Alzheimer's & dementia : the journal of the Alzheimer's Association, 20(12), 8661-8672","doi":"10.1002/alz.14313","pmid":"39445596","tags":["glp-1-receptor-agonists","semaglutide","brain-and-cognition"],"studyType":"cohort","evidenceStrength":"strong","keyFinding":"Semaglutide was associated with 40-70% reduced risk of first-time Alzheimer's diagnosis compared to seven other diabetes medications in 1,094,761 T2D patients, including a 41% lower risk vs. other GLP-1 agonists.","whyItMatters":"Alzheimer's disease affects over 55 million people worldwide with no cure. If semaglutide genuinely reduces AD risk by 40-70%, it could become a preventive strategy for the hundreds of millions of people with T2D who are already at elevated dementia risk. The finding that semaglutide outperforms even other GLP-1 agonists suggests something specific about its pharmacology may be neuroprotective.","specificNumbers":"116 million US patients in EHR database; 1,094,761 eligible T2DM patients; 7 emulated target trials; semaglutide vs. various comparator drugs.","methodology":"Emulated target trial design using nationwide US electronic health records (116 million patients). Seven comparisons of semaglutide vs. other antidiabetic medications among 1,094,761 eligible T2D patients. Outcome: first-ever AD diagnosis within 3 years. Cox proportional hazards and Kaplan-Meier analyses. Stratified by obesity status, gender, and age.","limitations":"Observational study — cannot prove semaglutide prevents AD. Target trial emulation reduces but doesn't eliminate confounding. AD diagnosis relies on clinical recognition, which may be inconsistent. Semaglutide users may differ from comparator groups in unmeasured ways (health-seeking behavior, socioeconomic status). Only T2D patients studied — generalizability to non-diabetic populations unknown."},{"rthcId":"RPEP-09495","title":"Diffusion model assisted designing self-assembling collagen mimetic peptides as biocompatible materials.","authors":"Wang, Xinglong; Xu, Kangjie; Ma, Lingling; Sun, Ruoxi; Wang, Kun; Wang, Ruiyan; Zhang, Junli; Tao, Wenwen; Linghu, Kai; Yu, Shuyao; Zhou, Jingwen","year":2024,"journal":"Briefings in bioinformatics, 26(1)","doi":"10.1093/bib/bbae622","pmid":"39688478","tags":["collagen-peptides","peptide-engineering"],"studyType":"in vitro","evidenceStrength":"moderate","keyFinding":"AI diffusion model generated collagen mimetic peptides with 66% triple-helix self-assembly success rate, hydrogel formation at 0.08% w/v concentration, and osteoblast differentiation activity for potential bone regeneration applications.","whyItMatters":"Collagen is the most abundant protein in the human body and a key material for tissue engineering, wound healing, and bone regeneration. Designing collagen-like peptides by trial and error is slow — AI diffusion models can explore the sequence space orders of magnitude faster, creating designer biomaterials with specific self-assembly and biological properties.","specificNumbers":"66% of synthetic CMPs self-assembled into triple helices; diffusion model trained on multiple human collagen types.","methodology":"Trained a diffusion model on human collagen sequences to generate CMPs. Developed a melting temperature prediction model (PC=0.95 cross-validation, PC=0.8 for synthetic CMPs). Validated self-assembly by Tm measurements. Tested chemically synthesized short CMPs and recombinantly expressed long CMPs for hydrogel formation and osteoblast differentiation.","limitations":"Only a subset of generated CMPs were experimentally validated. The osteoblast differentiation results are preliminary (in vitro only). In vivo bone regeneration efficacy not tested. The diffusion model was trained on human collagen, which may limit diversity. Long-term stability of CMP hydrogels not assessed. Manufacturing cost vs. natural collagen extracts not compared."},{"rthcId":"RPEP-09496","title":"Obstacles, research progress, and prospects of oral delivery of bioactive peptides: a comprehensive review.","authors":"Wang, Xinyu; Yang, Zeyao; Zhang, Wangang; Xing, Lujuan; Luo, Ruiming; Cao, Songmin","year":2024,"journal":"Frontiers in nutrition, 11, 1496706","doi":"10.3389/fnut.2024.1496706","pmid":"39610876","tags":["oral-peptide-delivery","drug-delivery-systems","peptide-engineering"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Three major barriers limit oral bioactive peptide delivery — bitter taste, GI instability, and poor transmembrane transport — with emerging solutions including chemical modification, osmotic technology, liposomes, nanoparticles, and hydrogels showing varying degrees of success.","whyItMatters":"Peptide drugs and functional food peptides are one of the fastest-growing sectors in pharma and nutrition, but the inability to take them orally is the single biggest barrier to widespread use. Solving oral delivery would transform peptide therapeutics — replacing daily injections for millions of diabetes, obesity, and hormone therapy patients with simple pills.","specificNumbers":"Three major barrier categories: bitter taste, GI environmental instability, and transmembrane transport limitations.","methodology":"Comprehensive literature review covering factors affecting oral bioactive peptide absorption, current enhancement technologies, and delivery system platforms (liposomes, emulsions, polymer nanoparticles, hydrogels) for oral peptide delivery.","limitations":"Review article — does not present new experimental data. Many delivery technologies reviewed are still at the lab scale. Head-to-head comparisons between different approaches are largely absent. Cost-effectiveness and manufacturing scalability of advanced delivery systems are often overlooked. Regulatory pathways for novel delivery systems add complexity and time."},{"rthcId":"RPEP-09497","title":"Rigid-flexible nanocarriers loaded with active peptides for antioxidant and anti-inflammatory applications in skin.","authors":"Wang, Yan; Lin, Jialiang; Yu, Zihao; Cheng, Jinbo; Cheng, Jianhua; Cui, Weikang","year":2024,"journal":"Colloids and surfaces. B, Biointerfaces, 236, 113772","doi":"10.1016/j.colsurfb.2024.113772","pmid":"38394858","tags":["ghk-cu","skin-health","drug-delivery"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Rigid-flexible liposome nanocarriers protected GHK-Cu from enzymatic degradation and enabled sustained release, countering skin cell aging through Nrf2, SIRT1, and COX-2/PGE2 pathway modulation.","whyItMatters":"Copper peptide GHK-Cu is one of the most evidence-backed anti-aging ingredients, but its instability limits practical use. A delivery system that protects GHK-Cu and releases it gradually into skin cells could make this peptide's benefits more accessible in real-world skincare formulations.","specificNumbers":"The nanocarriers were tested at multiple polyol ratios. Enhanced skin penetration and sustained release profiles were confirmed versus free peptide controls.","methodology":"Developed liposome nanocarriers with different polyol modifications for GHK-Cu encapsulation. Characterized loading rate, stability, release kinetics, and enzyme resistance in vitro. Evaluated antioxidant and anti-inflammatory effects in cell models.","limitations":"In vitro study only — no human skin penetration or clinical aging outcomes measured. Liposome stability during long-term storage not fully characterized. Cost of liposome manufacturing may limit commercial viability."},{"rthcId":"RPEP-09498","title":"Targeted Affinity Purification and Mechanism of Action of Angiotensin-Converting Enzyme (ACE) Inhibitory Peptides from Sea Cucumber Gonads.","authors":"Wang, Yangduo; Chen, Shicheng; Shi, Wenzheng; Liu, Shuji; Chen, Xiaoting; Pan, Nan; Wang, Xiaoyan; Su, Yongchang; Liu, Zhiyu","year":2024,"journal":"Marine drugs, 22(2)","doi":"10.3390/md22020090","pmid":"38393061","tags":["bioactive-peptides","cardiovascular-health"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"The sea cucumber-derived peptide HDWWKER significantly decreased systolic blood pressure in spontaneously hypertensive rats after IV administration, validating targeted affinity purification combined with computational drug discovery for ACE inhibitor screening.","whyItMatters":"This study validates a novel pipeline: targeted affinity purification + computational screening → in vivo blood pressure reduction. Most food-derived ACE inhibitor studies stop at in vitro testing. Demonstrating actual blood pressure lowering in hypertensive animals significantly strengthens the case for marine-derived antihypertensive peptides.","specificNumbers":"Peptides smaller than 3 kDa showed the best ACE inhibitory activity. Multiple peptide sequences were identified and confirmed by molecular docking.","methodology":"Alcalase hydrolysis of sea cucumber gonads → ultrafiltration (<3 kDa) → ACE gel affinity chromatography → RP-HPLC → LC-MS/MS identification → SBVS filtering (20 peptides) → synthesis of top 3 → ACE inhibition kinetics → molecular docking and dynamics → SHR blood pressure testing (IV administration).","limitations":"HDWWKER was tested IV, not orally — oral bioavailability is unknown. The IC50 values are relatively high compared to pharmaceutical ACE inhibitors. Only short-term blood pressure effects assessed. Noncompetitive inhibition mechanism is less potent than competitive. Affinity purification introduces bias toward certain binding modes."},{"rthcId":"RPEP-09499","title":"Antimicrobial peptides and proteins against drug-resistant pathogens.","authors":"Wang, Yeji; Song, Minghui; Chang, Wenqiang","year":2024,"journal":"Cell surface (Amsterdam, Netherlands), 12, 100135","doi":"10.1016/j.tcsw.2024.100135","pmid":"39687062","tags":["antimicrobial-peptides","immune-function"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Antimicrobial peptides combat drug-resistant pathogens through multiple mechanisms (membrane disruption, cell wall targeting, biofilm elimination, intracellular effects, immune modulation), but face challenges of toxicity, selectivity, stability, and immunogenicity.","whyItMatters":"Antimicrobial resistance kills over 1.2 million people annually. With the conventional antibiotic pipeline drying up, AMPs represent one of the most promising alternative approaches. Understanding both their mechanisms and limitations is essential for developing the next generation of anti-infective therapeutics.","specificNumbers":"The review covers AMPs from multiple natural sources and discusses AI prediction methods for novel peptide design.","methodology":"Comprehensive review of antimicrobial peptides and proteins against drug-resistant pathogens, covering natural, synthetic, and AI-predicted sources, mechanisms of action, immune modulation, and current limitations.","limitations":"Review article — does not present new experimental data. The field's biggest challenge (balancing antimicrobial potency with human cell safety) remains largely unsolved. Few AMPs have progressed through clinical trials. Manufacturing costs remain high compared to small-molecule antibiotics."},{"rthcId":"RPEP-09500","title":"Comparative effectiveness and tolerability of calcitonin gene-related peptide (CGRP) monoclonal antibodies and onabotulinumtoxinA in chronic migraine: A multicenter, real-world study in Taiwan.","authors":"Wang, Yen-Feng; Yang, Fu-Chi; Chen, Lu-An; Chang, Ting-Yu; Su, Hui-Chen; Yang, Chun-Pai; Tu, Yi-Hsien; Tzeng, Yi-Shiang; Chen, Shih-Pin; Fuh, Jong-Ling; Lai, Kuan-Lin; Ling, Yu-Hsiang; Chen, Wei-Ta; Wang, Shuu-Jiun","year":2024,"journal":"European journal of neurology, 31(9), e16372","doi":"10.1111/ene.16372","pmid":"38837528","tags":["cgrp","neurological-conditions"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"CGRP monoclonal antibodies achieved significantly greater migraine day reduction (-13.0 vs. -8.7 days), higher responder rates (74.7% vs. 50.7%), and fewer adverse events (6.0% vs. 21.0%) compared to onabotulinumtoxinA in chronic migraine patients, including difficult-to-treat cases.","whyItMatters":"Chronic migraine patients need the most effective treatment available, and many have failed multiple preventives. This large real-world comparison provides practical guidance that clinical trials haven't delivered — showing CGRP mAbs outperform the established standard (onabotulinumtoxinA) even in the hardest-to-treat patients, with better tolerability.","specificNumbers":"The study included patients from multiple centers in Taiwan, with outcomes measured at 6 months. Both treatments significantly reduced monthly migraine days. Difficult-to-treat patients (3+ prior preventive failures) were analyzed separately.","methodology":"Multicenter retrospective analysis of prospectively collected data from chronic migraine patients treated with CGRP mAbs (n=316) or onabotulinumtoxinA (n=333) in Taiwan. Outcomes at 6 months: monthly migraine days (prospective diaries), ≥50% responder rate, MIDAS disability scores, and adverse events. Subgroup analyses for difficult-to-treat and medication-overuse headache patients.","limitations":"Retrospective analysis — not a randomized controlled trial. Treatment selection bias (patients may have received CGRP mAbs vs. Botox for different reasons). All data from Taiwan — results may not generalize to other populations. The specific CGRP mAbs used weren't differentiated (erenumab, galcanezumab, fremanezumab). Follow-up limited to 6 months."},{"rthcId":"RPEP-09501","title":"Hyaluronan Scaffold Decorated with Bifunctional Peptide Promotes Wound Healing via Antibacterial and Anti-Inflammatory.","authors":"Wang, Yingzi; Zhao, Mingda; Zou, Yaping; Wang, Xiaojuan; Zhang, Min; Sun, Yong","year":2024,"journal":"Biomacromolecules, 25(12), 7850-7860","doi":"10.1021/acs.biomac.4c01130","pmid":"39586057","tags":["antimicrobial-peptides","skin-health","wound-healing"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Cathelicidin-BF-decorated hyaluronan scaffold (HAG-g-C) provided dual antibacterial and anti-inflammatory function, killing S. aureus and E. coli while driving M1-to-M2 macrophage polarization and accelerating infected wound healing in mice.","whyItMatters":"Infected wounds are a major clinical challenge, especially with rising antibiotic resistance. A wound dressing that simultaneously kills bacteria AND shifts the immune response from inflammation to healing addresses both problems at once — potentially reducing healing time and antibiotic use for infected wounds.","specificNumbers":"Effective against both Staphylococcus aureus and Escherichia coli in vitro. Promoted M1-to-M2 macrophage transition.","methodology":"Designed HAG-g-C scaffold by cross-linking hyaluronan with gallic acid-modified gelatin and decorating with cathelicidin-BF antimicrobial peptide. Tested antibacterial activity against S. aureus and E. coli in vitro. Assessed macrophage polarization (M1→M2). Evaluated wound healing in S. aureus-infected full-thickness skin defect mouse model over 12 days.","limitations":"Mouse model — wound healing differs between mice and humans. Only tested against two bacterial species. Long-term degradation profile of the scaffold not fully characterized. Manufacturing complexity and cost vs. conventional wound dressings not assessed. Single antimicrobial peptide — synergy with additional antimicrobials not explored."},{"rthcId":"RPEP-09502","title":"pH-Responsive Co-Assembled Peptide Hydrogel to Inhibit Drug-Resistant Bacterial Infection and Promote Wound Healing.","authors":"Wang, Yu; Shi, Jingru; Wang, Mengyao; Zhang, Lingjiao; Wang, Rui; Zhang, Junjie; Qing, Huiling; Duan, Jinyou; Zhang, Xiaoli; Pu, Guojuan","year":2024,"journal":"ACS applied materials & interfaces, 16(15), 18400-18410","doi":"10.1021/acsami.3c18436","pmid":"38576193","tags":["antimicrobial-peptides","wound-healing","drug-delivery"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"pH-responsive co-assembled peptide-curcumin hydrogel reduced curcumin's MIC against MRSA 10-fold through dual antibacterial mechanisms (cationic peptide membrane disruption + curcumin release) and promoted wound healing in an MRSA-infected mouse model.","whyItMatters":"MRSA kills thousands annually and is resistant to most antibiotics. This approach uses a peptide that bacteria can't easily resist (membrane disruption) combined with curcumin (a natural antimicrobial) in a smart hydrogel that activates at wound pH. The 10-fold MIC reduction means effective killing at much lower, safer doses.","specificNumbers":"The hydrogel formed at pH ~7.8 and released curcumin in weakly acidic conditions typical of infected wounds. Effective against MRSA in vitro and in mouse wound models.","methodology":"Synthesized cationic short peptide Nap-FFKKK. Co-assembled with curcumin at pH ~7.8 to form hydrogel. Characterized pH-responsive curcumin release at pH ~5.5. Tested MIC against MRSA in vitro. Evaluated wound healing in MRSA-infected mouse wound model.","limitations":"Mouse wound model — human wound healing may differ. Only tested against MRSA — broader spectrum activity unknown. Curcumin bioavailability and stability in wound environments needs more study. Manufacturing complexity of the peptide-curcumin co-assembly system. Long-term wound healing outcomes beyond the study period not assessed."},{"rthcId":"RPEP-09503","title":"Identification and characterization of vasoactive intestinal peptide receptor antagonists with high-affinity and potent anti-leukemia activity.","authors":"Wang, Yuou; Sen-Majumdar, Anish; Li, Jian-Ming; Sarkar, Srijon; Passang, Tenzin; Li, Yiwen; Cohen, Jamie; Chen, Zihan; Chaudagar, Kiranj; Das, Pankoj Kumar; Wang, Shuhua; Bruk, Nabute; Papadantonakis, Nikolaos; Giver, Cynthia R; Waller, Edmund K","year":2024,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2024.11.08.622716","pmid":"39605448","tags":["vip","cancer-research","immune-function"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"VIP receptor antagonists ANT308 and ANT195, identified through combinatorial library screening with computational binding prediction, potently activated T cells and induced anti-leukemia responses in mouse AML models and human AML patient samples.","whyItMatters":"Acute myeloid leukemia (AML) is an aggressive blood cancer with poor outcomes, especially after relapse. VIP receptor blockade represents a completely different immunotherapy approach than checkpoint inhibitors — unleashing T cells by removing a neuropeptide-mediated brake. ANT308's activity on patient-derived T cells suggests this could help AML patients who have failed other treatments.","specificNumbers":"The combinatorial library screened multiple C-terminal sequence variations. Lead candidates showed improved receptor binding affinity and plasma stability over VIPhyb.","methodology":"Created combinatorial library of VIPhyb C-terminal variants. In silico docking scored binding to VPAC1/VPAC2. Synthesized 15 top peptides. Tested T cell activation (mouse and human) in vitro. Evaluated anti-leukemia activity in C1498 myeloid leukemia mouse model (daily SC injections). Validated ANT308 mechanism in CD8+ T cells from AML patients.","limitations":"Animal model (C1498 in C57Bl/6) — may not fully replicate human AML. Daily subcutaneous injections may limit patient compliance. In vitro human T cell activation doesn't guarantee in vivo anti-leukemia response. The peptide antagonists' pharmacokinetics and potential off-target effects (VIP has many physiological roles) need assessment. Small-scale patient sample testing."},{"rthcId":"RPEP-09504","title":"Activation of pro-resolving pathways mediate the therapeutic effects of thymosin beta-4 during Pseudomonas aeruginosa-induced keratitis.","authors":"Wang, Yuxin; Banga, Loveleen; Ebrahim, Abdul Shukkur; Carion, Thomas W; Sosne, Gabriel; Berger, Elizabeth A","year":2024,"journal":"Frontiers in immunology, 15, 1458684","doi":"10.3389/fimmu.2024.1458684","pmid":"39380984","tags":["thymosin-beta-4","immune-function","inflammation"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Thymosin beta-4 resolves bacterial keratitis inflammation by activating 5-LOX and 12/15-LOX enzymes, generating specialized pro-resolving mediators (lipoxins, resolvins), and directly enhancing macrophage phagocytosis through SPM pathway activation.","whyItMatters":"Bacterial keratitis can cause blindness, and current treatments (antibiotics alone) don't address the inflammatory corneal damage. Tβ4 is the first peptide shown to activate natural resolution pathways in the eye, offering a mechanistic rationale for combining it with antibiotics to not only clear infection but actively promote healing and prevent vision loss.","specificNumbers":"Tβ4 treatment modulated SPM pathways in the Pseudomonas aeruginosa keratitis model, enhancing bacterial killing while reducing inflammatory markers.","methodology":"In vivo Pseudomonas aeruginosa-induced bacterial keratitis mouse model treated with adjunctive Tβ4. Assessed LOX enzyme expression, SPM end products (lipoxins, resolvins), and SPM receptor levels in corneal tissue. In vitro validation using LPS-stimulated RAW 264.7 macrophages with siRNA knockdown of Tβ4 and LOX enzymes. Tested phagocytosis and efferocytosis mechanisms.","limitations":"Mouse corneal infection model — human keratitis may involve additional pathogens and inflammatory mechanisms. Only Pseudomonas aeruginosa tested — response to other keratitis-causing bacteria unknown. The distinction between direct (phagocytosis) and indirect (efferocytosis) SPM-mediated effects needs further clarification. Clinical translation requires human corneal studies."},{"rthcId":"RPEP-09505","title":"Screening and Constructing of Novel Angiotensin I-Converting Enzyme Inhibiting Peptides from Walnut Protein Isolate and Their Mechanisms of Action: A Merged In Silico and In Vitro Study.","authors":"Wang, Yuzhen; Tang, Hengkuan; Deng, Xinyue; Shen, Yijie; Tang, Mingjian; Wang, Fengjun","year":2024,"journal":"Plant foods for human nutrition (Dordrecht, Netherlands), 79(1), 48-58","doi":"10.1007/s11130-023-01122-1","pmid":"37962805","tags":["bioactive-peptides","cardiovascular-health"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Three ACE-inhibiting peptides from walnut protein — including the novel designed peptide IKQ — block ACE through anti-competitive inhibition and promote nitric oxide production in human endothelial cells without toxicity.","whyItMatters":"Finding natural ACE inhibitors in everyday foods like walnuts opens the door to functional food products that support blood pressure management — especially noteworthy because these peptides use an unusual inhibition mechanism that could complement existing drugs.","specificNumbers":"Optimal ultrasonic pretreatment: 15 minutes at 400 watts. Multiple ACE-inhibiting peptide sequences identified and validated by in silico and in vitro methods.","methodology":"Walnut protein isolate was extracted with optimized ultrasound (400 W, 15 min), hydrolyzed enzymatically, and fractionated via ultrafiltration, ion exchange chromatography, and LC-MS/MS. Peptides were screened in silico (ADMET, molecular docking) and validated with in vitro ACE inhibition assays and HUVEC cell viability/NO assays.","limitations":"Entirely in vitro and computational — no evidence these peptides survive human digestion, reach the bloodstream, or lower blood pressure in a living organism. The 21.7% utilization rate is a computational estimate, not measured in vivo. Anti-competitive inhibition is interesting but its practical advantage over competitive inhibition is unproven."},{"rthcId":"RPEP-09506","title":"Semaglutide promotes the transition of microglia from M1 to M2 type to reduce brain inflammation in APP/PS1/tau mice.","authors":"Wang, Zhao-Jun; Han, Wei-Na; Chai, Shi-Fan; Li, Yan; Fu, Chao-Jing; Wang, Chen-Fang; Cai, Hong-Yan; Li, Xin-Yi; Wang, Xiao; Hölscher, Christian; Wu, Mei-Na","year":2024,"journal":"Neuroscience, 563, 222-234","doi":"10.1016/j.neuroscience.2024.11.022","pmid":"39547338","tags":["glp-1-agonists","semaglutide","neurological-conditions","inflammation"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Semaglutide (25 nmol/kg IP every 2 days for 30 days) promoted M1-to-M2 microglial transition in 3xTg Alzheimer's mice, reducing neuroinflammation, decreasing hippocampal amyloid-β deposits, and improving memory performance.","whyItMatters":"Semaglutide is already widely prescribed for diabetes and obesity. If it can also calm brain inflammation and slow Alzheimer's progression — as this animal study suggests — it could be repurposed for neurodegenerative disease, potentially helping millions of people.","specificNumbers":"Four groups of mice tested: wild-type and 3xTg Alzheimer's mice, each with PBS or semaglutide. Treatment started at 7 months of age.","methodology":"Seven-month-old 3xTg (APP/PS1/tau) and wild-type mice were divided into four groups: WT+PBS, 3xTg+PBS, WT+semaglutide, 3xTg+semaglutide. Semaglutide (25 nmol/kg) was injected intraperitoneally every 2 days for 30 days. Behavioral tests assessed memory; molecular analyses measured inflammatory markers, microglial polarization, and amyloid deposition. BV2 microglial cells were used for in vitro confirmation.","limitations":"Mouse model — the 3xTg model doesn't perfectly replicate human Alzheimer's. Intraperitoneal dosing differs from human subcutaneous injection. 30-day treatment is short relative to human disease progression. Whether microglial M1/M2 polarization translates cleanly to human brain immune responses is debated."},{"rthcId":"RPEP-09507","title":"Interplay between Antimicrobial Peptides and Amyloid Proteins in Host Defense and Disease Modulation.","authors":"Wani, Naiem Ahmad; Gazit, Ehud; Ramamoorthy, Ayyalusamy","year":2024,"journal":"Langmuir : the ACS journal of surfaces and colloids, 40(48), 25355-25366","doi":"10.1021/acs.langmuir.4c03123","pmid":"39564995","tags":["antimicrobial-peptides","neurological-conditions"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"AMPs and amyloid proteins exhibit bidirectional cross-talk: AMPs modulate amyloid aggregation, fibril formation, and toxicity through diverse mechanisms, while amyloid proteins themselves demonstrate antimicrobial activity.","whyItMatters":"If Alzheimer's amyloid plaques are partly an antimicrobial defense gone haywire, it fundamentally changes how we think about the disease — and could explain why simply clearing plaques hasn't cured Alzheimer's. Understanding this cross-talk could lead to therapies that address root causes rather than symptoms.","specificNumbers":"The review covers multiple classes of AMPs and amyloid proteins, examining their structural and functional overlaps.","methodology":"Narrative review synthesizing literature on the structural similarities, functional interactions, and therapeutic implications of antimicrobial peptide–amyloid protein cross-talk.","limitations":"As a review, no new experimental data is presented. Many proposed mechanisms are still hypothetical and need direct experimental validation. The relative importance of antimicrobial versus pathological amyloid functions in human disease remains unclear."},{"rthcId":"RPEP-09508","title":"A microfluidic in vitro method predicting the fate of peptide drugs after subcutaneous administration.","authors":"Wanselius, Marcus; Abrahmsén-Alami, Susanna; Hanafy, Belal I; Mazza, Mariarosa; Hansson, Per","year":2024,"journal":"International journal of pharmaceutics, 667(Pt A), 124849","doi":"10.1016/j.ijpharm.2024.124849","pmid":"39454976","tags":["drug-delivery","peptide-chemistry"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"The microfluidics interaction study (MIS) method correctly ranked peptide drugs by their subcutaneous absorption rate constants, matching in vivo human data, and distinguished between electrostatic HA-binding and non-electrostatic aggregation mechanisms.","whyItMatters":"Developing peptide drugs for subcutaneous injection currently requires extensive animal testing because no good lab test predicts absorption. This microfluidic method could dramatically speed up drug development and reduce animal testing by providing accurate early-stage predictions.","specificNumbers":"The system was validated against multiple peptide drugs with known in vivo absorption profiles.","methodology":"A microfluidic system with polyelectrolyte microgel networks responsive to charged peptides was used to measure interaction strength with hyaluronic acid, aggregation tendency, and transport properties for seven peptide drugs. Results were compared with the commercial SCISSOR system and published in vivo absorption data.","limitations":"The system mimics HA interactions but doesn't capture blood flow, lymphatic drainage, immune cell interactions, or the full complexity of subcutaneous tissue. Validated against a limited set of peptide drugs — broader validation needed. The proposed charge-based mechanism for absorption rate differences needs further confirmation."},{"rthcId":"RPEP-09509","title":"Understanding mechanisms of negative food effect for voclosporin using physiologically based pharmacokinetic modeling.","authors":"Watanabe, Ayahisa; Akazawa, Takanori; Fujiu, Motohiro","year":2024,"journal":"Drug metabolism and pharmacokinetics, 59, 101032","doi":"10.1016/j.dmpk.2024.101032","pmid":"39432969","tags":["cyclosporin-analogs","drug-delivery","autoimmune-conditions"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"PBPK modeling identified food adsorption in the GI tract as the primary mechanism behind voclosporin's negative food effect, successfully reproducing clinical pharmacokinetic profiles in both fasted and fed states.","whyItMatters":"For lupus nephritis patients taking voclosporin, understanding why food reduces absorption ensures proper dosing instructions. This modeling approach could also help predict food effects for other cyclic peptide drugs in development.","specificNumbers":"The PBPK model successfully reproduced clinical trial observations of reduced bioavailability in the fed state.","methodology":"Physiologically based pharmacokinetic modeling incorporating P-glycoprotein transport, CYP3A4 metabolism, and membrane permeability data from human iPSC-derived intestinal epithelial cells. Simulations were validated against clinical trial data in fasted and fed conditions and replicated in a rat model.","limitations":"Computational modeling study — conclusions depend on the accuracy of input parameters and model assumptions. Doesn't account for all sources of patient-to-patient variability. The food adsorption mechanism is proposed based on modeling fit, not directly measured."},{"rthcId":"RPEP-09510","title":"Pneumococcal surface protein A (PspA) prevents killing of Streptococcus pneumoniae by indolicidin.","authors":"Waz, Natalha T; Milani, Barbara; Assoni, Lucas; Coelho, Guilherme Rabelo; Sciani, Juliana M; Parisotto, Thaís; Ferraz, Lucio F C; Hakansson, Anders P; Converso, Thiago R; Darrieux, Michelle","year":2024,"journal":"Scientific reports, 14(1), 23517","doi":"10.1038/s41598-024-73564-9","pmid":"39384882","tags":["antimicrobial-peptides","immune-function"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"PspA-negative pneumococci were significantly more sensitive to indolicidin-induced killing, and mass spectrometry confirmed direct PspA-indolicidin binding, demonstrating that PspA provides broad-spectrum protection against cationic antimicrobial peptides.","whyItMatters":"Understanding how bacteria evade our natural antimicrobial defenses is crucial for developing effective vaccines and peptide-based antibiotics. PspA's role as a broad AMP shield — not just specific to lactoferricins — makes it an even more attractive vaccine target.","specificNumbers":"PspA-negative pneumococci showed significantly greater sensitivity to indolicidin-induced killing compared to PspA-positive bacteria.","methodology":"Researchers compared indolicidin susceptibility between PspA-expressing and PspA-negative S. pneumoniae strains using killing assays. Chemical removal of choline-binding proteins, capsule-negative mutants, anti-PspA antibodies, and soluble PspA competition were tested. Direct binding was confirmed by mass spectrometry.","limitations":"In vitro killing assays don't capture the full complexity of lung or blood infections. Only one AMP (indolicidin) was tested beyond lactoferricins — the breadth of PspA's protective effect across all human AMPs is unknown. Strain-specific differences in PspA could affect generalizability."},{"rthcId":"RPEP-09511","title":"Effect of Milk Protein-Polyphenol Conjugate on the Regulation of GLP-1 Hormone.","authors":"Wazzan, Huda Abdulrahim; Abraham, Amanda N; Saiara, Noshin; Anand, Sushil; Gill, Harsharn; Shukla, Ravi","year":2024,"journal":"Foods (Basel, Switzerland), 13(12)","doi":"10.3390/foods13121935","pmid":"38928876","tags":["glp-1-agonists","lactoferrin","metabolic-health"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Apo-lactoferrin-EGCG conjugates significantly upregulated GLP-1 gene and protein expression in NCI-H716 human colon cells beyond what either lactoferrin or EGCG achieved separately, while the conjugation protected EGCG from degradation.","whyItMatters":"GLP-1 is the same pathway behind semaglutide and other weight-loss drugs. Finding food-based ingredients that naturally boost GLP-1 could lead to functional foods or supplements that support appetite control and metabolic health without prescription drugs.","specificNumbers":"The conjugate showed enhanced GLP-1 regulation compared to lactoferrin or EGCG alone in cell-based assays.","methodology":"Apo-LF-EGCG conjugates were synthesized and characterized structurally. GLP-1 regulation was measured using qRT-PCR (gene expression) and ELISA (protein expression) in NCI-H716 human colon cell line. Antioxidant properties of the conjugate were also assessed.","limitations":"In vitro cell culture only — no evidence this conjugate boosts GLP-1 in a living person. The magnitude of GLP-1 increase is likely far smaller than pharmaceutical GLP-1 agonists. Whether the conjugate survives digestion and reaches colon cells intact is unknown. NCI-H716 is a cancer cell line, which may not perfectly represent normal gut hormone-producing cells."},{"rthcId":"RPEP-09512","title":"Molecular connectomics reveals a glucagon-like peptide 1-sensitive neural circuit for satiety.","authors":"Webster, Addison N; Becker, Jordan J; Li, Chia; Schwalbe, Dana C; Kerspern, Damien; Karolczak, Eva O; Bundon, Catherine B; Onoharigho, Roberta A; Crook, Maisie; Jalil, Maira; Godschall, Elizabeth N; Dame, Emily G; Dawer, Adam; Belmont-Rausch, Dylan Matthew; Pers, Tune H; Lutas, Andrew; Habib, Naomi; Güler, Ali D; Krashes, Michael J; Campbell, John N","year":2024,"journal":"Nature metabolism, 6(12), 2354-2373","doi":"10.1038/s42255-024-01168-8","pmid":"39627618","tags":["glp-1-agonists","neurological-conditions","weight-management"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"TRH-expressing arcuate hypothalamic neurons (TRHArc) express GLP-1 receptors, are activated by liraglutide, inhibit AgRP hunger neurons, and are required for liraglutide's full body weight effects — identifying a specific neural circuit for GLP-1 drug-mediated appetite suppression.","whyItMatters":"Understanding exactly which brain circuits GLP-1 drugs activate could lead to more targeted appetite-suppressing medications with fewer side effects, and help explain why these drugs work so remarkably well for weight loss.","specificNumbers":"At least 21 afferent neuron subtypes identified connecting to AgRP neurons. Key GLP-1-sensitive circuit originated from the dorsomedial hypothalamus (DMH).","methodology":"Researchers developed a molecular connectomics method combining rabies virus-based retrograde tracing with single-nucleus RNA sequencing to map afferent inputs to AgRP neurons in mice. Functional validation used optogenetic/chemogenetic activation and silencing of TRHArc neurons, plus liraglutide challenge experiments.","limitations":"Done entirely in mice — human hypothalamic circuits may differ. The molecular connectomics method maps physical connections but may miss some functional complexity. TRHArc neurons are likely one of multiple circuits through which GLP-1 drugs affect appetite. Silencing TRHArc only partially attenuated liraglutide's effects, suggesting other circuits also contribute."},{"rthcId":"RPEP-09513","title":"Bulevirtide monotherapy in patients with chronic HDV: Efficacy and safety results through week 96 from a phase III randomized trial.","authors":"Wedemeyer, Heiner; Aleman, Soo; Brunetto, Maurizia; Blank, Antje; Andreone, Pietro; Bogomolov, Pavel; Chulanov, Vladimir; Mamonova, Nina; Geyvandova, Natalia; Morozov, Viacheslav; Sagalova, Olga; Stepanova, Tatyana; Berger, Annemarie; Ciesek, Sandra; Manuilov, Dmitry; Mercier, Renee-Claude; Da, Ben L; Chee, Grace M; Li, Mingyang; Flaherty, John F; Lau, Audrey H; Osinusi, Anu; Schulze Zur Wiesch, Julian; Cornberg, Markus; Zeuzem, Stefan; Lampertico, Pietro","year":2024,"journal":"Journal of hepatology, 81(4), 621-629","doi":"10.1016/j.jhep.2024.05.001","pmid":"38734383","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09514","title":"Loss of neuropeptide signalling alters temporal expression of mouse suprachiasmatic neuronal state and excitability.","authors":"Wegner, Sven; Belle, Mino D C; Chang, Pi-Shan; Hughes, Alun T L; Conibear, Alexandra E; Muir, Charlotte; Samuels, Rayna E; Piggins, Hugh D","year":2024,"journal":"The European journal of neuroscience, 60(11), 6617-6633","doi":"10.1111/ejn.16590","pmid":"39551976","tags":["vip","neurological-conditions","circadian-rhythm"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"VPAC2 receptor knockout mice exhibited loss of coordinated day-night variation in SCN neuronal excitability, with neurons manifesting random electrical states, lacking voltage-gated sodium current components, and showing altered responses to light-pathway input signals.","whyItMatters":"VIP is one of the most important neuropeptides in circadian biology. Understanding how it coordinates clock neuron activity could lead to treatments for circadian rhythm disorders, jet lag, shift work problems, and the many diseases linked to disrupted body clocks (metabolic syndrome, depression, cancer risk).","specificNumbers":"Recordings captured day-night variation in neuronal excitability across the circadian cycle in both knockout and wild-type mice.","methodology":"Patch-clamp electrophysiology recordings from SCN neurons in brain slices from Vipr2-/- (VPAC2 knockout) and Vipr2+/+ (wild-type) mice across the circadian cycle, measuring membrane properties, action potential thresholds, voltage-gated sodium currents, and responses to neurochemical mimics of light input.","limitations":"Complete genetic knockout of VPAC2 is more extreme than any natural variation in VIP signaling — results may overestimate the impact of partial VIP dysfunction. Mouse SCN organization may differ from humans. Brain slice preparations remove the SCN from its normal context, though this is standard methodology."},{"rthcId":"RPEP-09515","title":"Obstructive sleep apnea, the NLRP3 inflammasome and the potential effects of incretin therapies.","authors":"Wei, Michelle; Teske, Jennifer A; Mashaqi, Saif; Combs, Daniel","year":2024,"journal":"Frontiers in sleep, 3, 1524593","doi":"10.3389/frsle.2024.1524593","pmid":"41424495","tags":["glp-1-agonists","inflammation","cardiovascular-health","sleep-and-recovery"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"The NLRP3 inflammasome is activated by OSA's intermittent hypoxia cycle and drives cardiovascular/neurological complications through IL-1β and IL-18 release; GLP-1 receptor agonists show potential to suppress this inflammatory pathway beyond their weight-loss benefits.","whyItMatters":"OSA affects nearly a billion people worldwide and dramatically increases risk of heart attack, stroke, and dementia. Current treatment (CPAP) addresses the breathing obstruction but is poorly tolerated. GLP-1 drugs could offer a dual benefit — reducing weight to improve airway patency while independently calming the systemic inflammation that drives complications.","specificNumbers":"The review covers the intermittent hypoxia-NLRP3 pathway and its downstream effects including IL-1β and IL-18 release.","methodology":"Narrative review covering the molecular mechanisms of NLRP3 inflammasome activation by intermittent hypoxia in OSA, downstream cardiovascular and neurological effects, and the anti-inflammatory potential of incretin therapies including GLP-1 receptor agonists.","limitations":"Review article proposing a hypothesis — no clinical trials have specifically tested GLP-1 drugs for OSA-related NLRP3 inflammasome suppression. The anti-inflammatory effects of GLP-1 drugs on NLRP3 are largely from non-OSA contexts. Whether these drugs meaningfully reduce OSA complications independently of weight loss is unproven."},{"rthcId":"RPEP-09516","title":"Treatment with liraglutide or naltrexone-bupropion in patients with genetic obesity: a real-world study.","authors":"Welling, Mila S; de Groot, Cornelis J; Mohseni, Mostafa; Meeusen, Renate E H; Boon, Mariëtte R; van Haelst, Mieke M; van den Akker, Erica L T; van Rossum, Elisabeth F C","year":2024,"journal":"EClinicalMedicine, 74, 102709","doi":"10.1016/j.eclinm.2024.102709","pmid":"39050109","tags":["glp-1-agonists","liraglutide","weight-management","metabolic-health"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Liraglutide 3 mg produced median weight loss of 4.7% (MCGO) and 5.2% (HSGO) after 12 weeks at maximum dose, with significant improvements in appetite, fat mass, fasting glucose, and HbA1c in adults with genetic obesity.","whyItMatters":"People with genetic obesity have few effective treatment options — lifestyle interventions that work for common obesity often fail for them. Showing that GLP-1 drugs like liraglutide are effective in this population could transform care for thousands of people with rare genetic conditions driving severe obesity.","specificNumbers":"The study included adults with molecularly confirmed genetic obesity (MCGO) and highly suspected genetic obesity (HSGO), tracked at a specialized center.","methodology":"Real-world cohort study at Erasmus University Obesity Center, Rotterdam (March 2019–August 2023). 98 adults with molecularly confirmed (n=23) or suspected (n=75) genetic obesity received liraglutide 3 mg or naltrexone-bupropion per manufacturer protocol. Evaluation at 12 weeks on maximum/highest-tolerated dose assessed anthropometrics, body composition, metabolic markers, appetite, eating behavior, and quality of life.","limitations":"Real-world study without placebo control — can't definitively attribute all weight loss to medication. Short-term evaluation (12 weeks) doesn't address long-term efficacy or weight regain. The HSGO group lacked molecular confirmation, so some may not have true genetic obesity. Relatively small sample, especially the MCGO group (n=23)."},{"rthcId":"RPEP-09517","title":"Effects of an Angiotensin IV Analog on 3-Nitropropionic Acid-Induced Huntington's Disease-Like Symptoms in Rats.","authors":"Wells, Russell G; Azzam, Azzam F; Hiller, Amie L; Sardinia, Michael F","year":2024,"journal":"Journal of Huntington's disease, 13(1), 55-66","doi":"10.3233/JHD-231507","pmid":"38489193","tags":[],"studyType":"animal","evidenceStrength":"preliminary","keyFinding":"Dihexa (PNB-0408), an angiotensin IV analog previously shown to be neuroprotective in Alzheimer's and Parkinson's disease models, did NOT protect against Huntington's disease-like symptoms in rats. The 3-NP toxin successfully induced HD-like deficits — decreased weight gain, impaired spatial learning and memory, and marked motor dysfunction — but PNB-0408 administered alongside 3-NP failed to attenuate any of these deficits.\n\nThis is a negative result: the peptide analog that showed promise in other neurodegenerative diseases did not work in this Huntington's disease model.","whyItMatters":"Negative results are essential for honest science. Dihexa has generated significant interest in biohacking and nootropic communities for its purported cognitive enhancement properties. This study shows that its neuroprotective effects don't extend to all types of neurodegeneration — specifically, it failed in a Huntington's disease model. This helps define the boundaries of what this peptide analog can and cannot do.","specificNumbers":"40 male Wistar rats · 3 groups (vehicle, 3-NP, 3-NP + PNB-0408) · 5-week study period · no significant protective effect on weight, motor function, or cognition","methodology":"Randomized controlled animal study. Forty male Wistar rats were divided into three groups: vehicle control, 3-NP toxin only, and 3-NP plus PNB-0408 (Dihexa). The 3-NP mitochondrial toxin was administered chronically to induce Huntington's disease-like pathology. Body weight, motor function, and cognitive abilities (spatial learning and memory) were measured over 5 weeks, followed by euthanasia and histopathological brain analysis.","limitations":"This is a single animal study using a chemical-induced model of Huntington's disease (3-NP), which mimics metabolic aspects of HD but doesn't replicate the genetic cause (mutant huntingtin protein). The study used only male rats. PNB-0408 dosing and timing may not have been optimal. Results from one HD model don't rule out efficacy in genetic HD models."},{"rthcId":"RPEP-09518","title":"Rimegepant and atogepant: novel drugs providing innovative opportunities in the management of migraine.","authors":"Wells-Gatnik, William David; Pellesi, Lanfranco; Martelletti, Paolo","year":2024,"journal":"Expert review of neurotherapeutics, 24(11), 1107-1117","doi":"10.1080/14737175.2024.2401558","pmid":"39264231","tags":["cgrp","neurological-conditions"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Rimegepant and atogepant demonstrate significant clinical innovation in migraine therapy with approved indications for acute and preventive treatment, while data is emerging for expanded roles in pediatric, pregnancy, cluster headache, and post-CGRP-antibody-discontinuation populations.","whyItMatters":"Gepants fill an important gap — they're the first oral preventive migraine medications that target the CGRP pathway, offering an alternative for patients who can't tolerate or don't want injectable CGRP antibodies. Understanding their full potential could benefit the millions of migraine sufferers with limited options.","specificNumbers":"Rimegepant can be used acutely (as needed) or preventively (every other day). Atogepant is taken daily for prevention.","methodology":"Database search for 'Rimegepant OR Atogepant' yielding 240 results, refined to 42 studies through relevance assessment for narrative review synthesis.","limitations":"Review article — no new data generated. Data for expanded indications is limited or absent. The review notes that gepants remain underutilized, suggesting real-world adoption lags behind evidence. Long-term safety data for emerging populations (pediatric, pregnancy) is particularly sparse."},{"rthcId":"RPEP-09519","title":"Switching CGRP(r) MoAbs in migraine: what evidence?","authors":"Wells-Gatnik, William David; Martelletti, Paolo","year":2024,"journal":"Expert opinion on biological therapy, 24(5), 327-333","doi":"10.1080/14712598.2024.2354386","pmid":"38726800","tags":["cgrp","neurological-conditions"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Available data is insufficient to determine the efficacy of switching between CGRP receptor monoclonal antibodies following discontinuation of initial therapy, according to expert review aligned with European Headache Federation guidelines.","whyItMatters":"With ~50% of CGRP antibody users discontinuing treatment, the question of whether to try a different CGRP antibody is extremely common in clinical practice. Clarifying what the evidence says — and doesn't say — helps patients and doctors make informed decisions rather than operating on assumptions.","specificNumbers":"Approximately 50% of patients receiving CGRP antibodies discontinue therapy. Available switching data comes from small studies and case series.","methodology":"Database search for 'CGRP monoclonal antibody switch OR CGRP monoclonal antibody switching' to identify all available data on switching efficacy after CGRP MoAb discontinuation.","limitations":"Limited by the scarcity of available switching data — the review can only synthesize what exists. Expert opinion fills gaps where evidence is absent. The field is evolving rapidly, so conclusions may change as new studies are published."},{"rthcId":"RPEP-09520","title":"Inhibition of 2-AG hydrolysis alleviates posttraumatic headache attributed to mild traumatic brain injury.","authors":"Wen, Jie; Tanaka, Mikiei; Zhang, Yumin","year":2024,"journal":"The journal of headache and pain, 25(1), 115","doi":"10.1186/s10194-024-01817-z","pmid":"39014318","tags":["neurological-conditions","inflammation","pain-management"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"MJN110 (MAGL inhibitor) dose-dependently attenuated post-traumatic headache in mice after repetitive mild TBI by reducing CGRP expression and glial activation in the trigeminal ganglion and nucleus caudalis, with effects mediated through cannabinoid receptor activation.","whyItMatters":"Post-concussion headaches affect millions of people and current treatments are often inadequate. This study identifies a new therapeutic approach — boosting endocannabinoids to reduce CGRP-mediated pain — that could complement or provide an alternative to existing CGRP-targeting migraine drugs for post-traumatic headache.","specificNumbers":"Male C57BL/6J mice with repetitive mild TBI treated with MAGL inhibitor to boost endogenous 2-AG levels.","methodology":"Repetitive mild TBI was induced in male C57BL/6J mice using the CHIMERA model. Periorbital allodynia was measured with von Frey filaments. CGRP expression and glial activation were assessed by immunofluorescence in the trigeminal ganglion and nucleus caudalis. Endocannabinoid levels (2-AG, AEA, AA) were measured by mass spectrometry. MJN110 effects were tested with cannabinoid receptor antagonists and the 2-AG synthesis inhibitor DO34.","limitations":"Mouse model of TBI — human post-concussion headaches are more complex. Only male mice were used, despite known sex differences in both migraine and TBI outcomes. MJN110 is a research tool compound, not an approved drug. The CHIMERA model may not fully replicate the spectrum of human concussions. Long-term effects were not assessed."},{"rthcId":"RPEP-09521","title":"Comparative Efficacy of Semaglutide Versus Liraglutide or Efinopegdutide on Weight Loss in Obese Patients: A Systematic Review and Meta-Analysis.","authors":"Wen, Jimmy; How-Volkman, Christiane; Truong, Alina; Nadora, Denise; Bernstein, Ethan M; Akhtar, Muzammil; Puglisi, Jose; Frezza, Eldo","year":2024,"journal":"Cureus, 16(12), e75304","doi":"10.7759/cureus.75304","pmid":"39776746","tags":["semaglutide","glp-1-agonists","weight-management"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Semaglutide produced significantly greater weight loss than liraglutide in obese non-diabetic patients, but did not show a significant difference compared to efinopegdutide, with all drugs demonstrating primarily mild-to-moderate GI adverse events.","whyItMatters":"Most GLP-1 weight loss data comes from diabetic populations. This meta-analysis confirms semaglutide's superiority over liraglutide specifically in the non-diabetic obesity population — the patient group most likely to seek these drugs purely for weight management.","specificNumbers":"Direct comparison data analyzed for semaglutide versus liraglutide and efinopegdutide in non-diabetic obesity.","methodology":"Systematic review and meta-analysis following PRISMA guidelines. PubMed, Embase, and Cochrane Library were searched for direct comparative studies of semaglutide vs. other GLP-1 RAs (liraglutide, efinopegdutide) in patients with obesity without diabetes. Narrative synthesis and meta-analysis were performed.","limitations":"Limited number of direct comparison studies available, especially for efinopegdutide. Study durations and patient populations may vary across included trials. The non-significant difference between semaglutide and efinopegdutide could reflect small sample sizes rather than true equivalence. Long-term weight maintenance data is lacking."},{"rthcId":"RPEP-09522","title":"Semaglutide Versus Other Glucagon-Like Peptide-1 Agonists for Weight Loss in Type 2 Diabetes Patients: A Systematic Review and Meta-Analysis.","authors":"Wen, Jimmy; Nadora, Denise; Bernstein, Ethan; How-Volkman, Christiane; Truong, Alina; Akhtar, Muzammil; Prakash, Neha A; Puglisi, Jose; Frezza, Eldo","year":2024,"journal":"Cureus, 16(9), e69008","doi":"10.7759/cureus.69008","pmid":"39385875","tags":["semaglutide","glp-1-agonists","weight-management","metabolic-health"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Semaglutide showed significantly greater weight loss than liraglutide (mean difference -6.08 kg, 95% CI -8.40 to -3.75) in T2DM patients, while tirzepatide produced significantly greater weight loss than semaglutide (mean difference -3.78 kg, 95% CI -5.52 to -2.04).","whyItMatters":"With multiple GLP-1 drugs available, patients and doctors need evidence-based guidance on which produces the most weight loss. This meta-analysis provides the clearest head-to-head comparison yet, helping inform treatment choices for the millions of people with type 2 diabetes who need weight management.","specificNumbers":"Meta-analysis pooled data from multiple direct comparison trials of semaglutide versus other GLP-1 RAs in T2DM patients.","methodology":"Systematic review and meta-analysis following PRISMA guidelines. PubMed, Embase, and Cochrane Library were searched for studies comparing semaglutide with other GLP-1 RAs for weight loss in T2DM patients. Nine studies with 5,445 patients (mean age 60, mean follow-up 32.5 weeks) were included. Meta-analysis used SPSS version 29.","limitations":"Limited to 9 studies — few direct head-to-head trials exist. Mean follow-up of only 32.5 weeks may not capture long-term weight loss differences. The semaglutide vs. dulaglutide comparison didn't reach statistical significance. Different study designs and patient populations across included trials may introduce heterogeneity. Tirzepatide is technically a dual GIP/GLP-1 agonist, not a pure GLP-1 RA."},{"rthcId":"RPEP-09523","title":"Comparation of fixed-ratio (IDegLira and iGlarLixi) versus free combination of basal insulin and glucagon-like peptide-1 receptor agonist for uncontrolled type 2 diabetes: A systematic review and network meta-analysis.","authors":"Weng, Junling; Tao, Ying; Xu, Zian; Zhou, Shanyan; Xiao, Dunming; Zhu, Zhixu; Zheng, Ruizhi; Yang, Yi; Chen, Yingyao","year":2024,"journal":"Journal of evidence-based medicine, 17(2), 370-376","doi":"10.1111/jebm.12620","pmid":"38858300","tags":["glp-1-agonists","insulin","metabolic-health"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Fixed-ratio combinations (IDegLira, iGlarLixi) and free combinations of basal insulin + GLP-1RA showed comparable HbA1c reduction (MD 0.07%, 95% CI -0.17 to 0.30), but free combinations produced significantly greater weight loss (-2.06 kg) and blood pressure reductions.","whyItMatters":"Many diabetes patients eventually need both insulin and a GLP-1 drug. This comprehensive analysis helps clinicians and patients choose between the convenience of a single-pen combination versus the potentially better metabolic outcomes of separate injections.","specificNumbers":"Network meta-analysis included phase III clinical trials of IDegLira, iGlarLixi, and free combinations. Databases searched through April 2023.","methodology":"Network meta-analysis following PROSPERO registration (CRD42023409585). Eight databases searched through April 2023. 42 Phase III clinical trials (23,619 patients) with uncontrolled T2DM included. Treatments categorized as FRC, free combination, or neither. Primary outcomes: HbA1c, body weight, hypoglycemia. Secondary: blood pressure.","limitations":"Network meta-analysis comparing across trials rather than within direct head-to-head studies. The weight and blood pressure differences, while statistically significant, are modest in clinical terms. Different trial designs, patient populations, and dose titration protocols may introduce heterogeneity. Cost and availability differences between FRC and free combinations not assessed."},{"rthcId":"RPEP-09524","title":"Oral Delivery of the Vancomycin Derivative FU002 by a Surface-Modified Liposomal Nanocarrier.","authors":"Werner, Julia; Umstätter, Florian; Hertlein, Tobias; Mühlberg, Eric; Beijer, Barbro; Wohlfart, Sabrina; Zimmermann, Stefan; Haberkorn, Uwe; Ohlsen, Knut; Fricker, Gert; Mier, Walter; Uhl, Philipp","year":2024,"journal":"Advanced healthcare materials, 13(14), e2303654","doi":"10.1002/adhm.202303654","pmid":"38387090","tags":["antimicrobial-peptides","drug-delivery"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Liposomal FU002 coated with cyclic cell-penetrating peptides achieved oral bioavailability in rats and significant therapeutic efficacy against systemic infection in mice when administered orally, while maintaining antimicrobial activity in vitro and in vivo.","whyItMatters":"Turning injectable-only antibiotics into oral drugs would be transformative for healthcare — reducing hospitalizations, improving patient comfort, and expanding access in resource-limited settings. This proof-of-concept shows that nanotechnology can enable oral delivery of peptide antibiotics that were previously impossible to take by mouth.","specificNumbers":"Surface-modified liposomes showed significantly improved oral bioavailability compared to unformulated FU002.","methodology":"FU002 was incorporated into tetraether lipid-stabilized liposomes modified with cyclic cell-penetrating peptides. Caco-2 cell binding and cytotoxicity were assessed in vitro. Pharmacokinetics were studied in rats (oral vs. IV). Antimicrobial activity was tested in vitro and in a murine systemic infection model with oral dosing.","limitations":"Early-stage preclinical study in rodents — oral bioavailability improvement was demonstrated but absolute values weren't detailed in the abstract. The complexity and cost of manufacturing liposomal formulations with cell-penetrating peptides may limit scalability. Long-term safety of the nanocarrier components is unknown. Human gut conditions may differ from rodent models."},{"rthcId":"RPEP-09525","title":"Harnessing Endogenous Peptide Compounds as Potential Therapeutics for Severe Influenza.","authors":"West, Alison C; Harpur, Christopher M; Le Page, Mélanie A; Lam, Maggie; Hodges, Christopher; Ely, Lauren K; Gearing, Andrew J; Tate, Michelle D","year":2024,"journal":"The Journal of infectious diseases, 230(2), e384-e394","doi":"10.1093/infdis/jiad566","pmid":"38060822","tags":["growth-hormone-peptides","immune-function","inflammation"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Intranasal LAT9997 (6-amino acid growth hormone fragment) significantly improved survival in severe murine influenza by reducing viral burden, cytokine storm, neutrophil infiltration, vascular leak, and epithelial cell death while preserving protective alveolar macrophages, even when initiated after symptom onset.","whyItMatters":"Current flu treatments (like Tamiflu) only work if given very early. A treatment that works after severe disease develops — by calming the immune overreaction rather than just fighting the virus — could save lives during flu pandemics and severe seasonal outbreaks. Using a natural human peptide fragment reduces the risk of off-target effects.","specificNumbers":"LAT9997 is 6 amino acids (versus 16 in the parent compound LAT8881) and is linear rather than cyclic, making it easier to produce.","methodology":"Mice were infected with influenza virus to model severe disease. LAT8881 (16 aa cyclic) and LAT9997 (6 aa linear fragment) were administered intranasally from day 1 post-infection or after symptom onset. Outcomes: survival, lung pathology, damage markers, vascular leak, epithelial death, viral load, cytokines, immune cell infiltration. Structure-activity relationship studied by sequential amino acid trimming.","limitations":"Preclinical mouse model only — mouse and human immune responses to influenza differ significantly. Intranasal delivery may be challenging in severely ill patients who are intubated. The relationship between this growth hormone fragment and growth hormone receptor signaling needs clarification. Manufacturing and stability of the peptide for clinical use not addressed."},{"rthcId":"RPEP-09526","title":"Pharmacokinetic Properties of a Once-Weekly Fixed-Ratio Combination of Insulin Icodec and Semaglutide Compared with Separate Administration of Each Component in Individuals with Type 2 Diabetes Mellitus.","authors":"Westergaard, Lisbet; Alifrangis, Lene; Buckley, Stephen T; Coester, Hans Veit; Klitgaard, Thomas; Kristensen, Niels R; Nishimura, Erica; Nørgreen, Lea; Rocha, Thaís M P; Steensgaard, Dorte B; Vegge, Andreas; Plum-Mörschel, Leona","year":2024,"journal":"Clinical drug investigation, 44(11), 849-861","doi":"10.1007/s40261-024-01405-8","pmid":"39488821","tags":["semaglutide","glp-1-agonists","insulin","metabolic-health"],"studyType":"RCT","evidenceStrength":"moderate","keyFinding":"IcoSema preserves icodec PK (AUC ratio 1.06, Cmax ratio 1.12, within bioequivalence bounds) but produces a 99% higher semaglutide Cmax (ratio 1.99) occurring 72 hours earlier (12 vs 84 h), attributed to albumin binding competition at the injection site.","whyItMatters":"IcoSema could become the first once-weekly insulin-plus-GLP-1 combination — simplifying diabetes management to a single weekly injection. Understanding how the two drugs interact pharmacokinetically is essential for safe, effective dosing of the combination product.","specificNumbers":"31 participants with T2DM, ages 18-64, body weight 80-120 kg. Three-period crossover design comparing combined versus separate administration.","methodology":"Randomized, double-blind, three-period crossover study (NCT03789578) in 31 adults with T2DM (age 18-64, BMI-matched 80-120 kg, HbA1c 6.0-8.5%). Single SC injections of IcoSema (175 U icodec + 0.5 mg semaglutide), icodec alone, or semaglutide alone with 6-9 week washout. PK blood sampling to 840 hours post-dose. Supported by in vitro albumin binding and animal PK studies.","limitations":"Single-dose PK study — steady-state behavior may differ. The doubled semaglutide Cmax could theoretically increase gastrointestinal side effects, which was supported by more GI adverse events with IcoSema in this study. Only one dose level tested (175 U/0.5 mg). Small sample size (n=31) though adequate for PK crossover design."},{"rthcId":"RPEP-09527","title":"Formation of Nanofibrillar Self-Healing Hydrogels Using Antimicrobial Peptides.","authors":"Wiita, Elizabeth G; Toprakcioglu, Zenon; Jayaram, Akhila K; Knowles, Tuomas P J","year":2024,"journal":"ACS applied materials & interfaces, 16(35), 46167-46176","doi":"10.1021/acsami.4c11542","pmid":"39171944","tags":["antimicrobial-peptides","bioactive-peptides","peptide-chemistry"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"KLVFF (Aβ 16-20) self-assembles into nanofibrillar self-healing hydrogels with antibacterial and antifungal activity and no cytotoxicity toward mammalian cells, making it a candidate for antimicrobial wound care.","whyItMatters":"Drug-resistant infections are a growing crisis, and antimicrobial wound dressings are urgently needed. A self-healing hydrogel that kills germs, is biocompatible, and can be made from a simple five-amino-acid peptide could be manufactured affordably and applied easily to wounds.","specificNumbers":"KLVFF — a 5-amino-acid sequence from amyloid-beta — formed nanofibrillar networks with self-healing capability and demonstrated antimicrobial effects.","methodology":"KLVFF peptide was characterized for self-assembly into hydrogel formation, nanostructure (fibrillar network), rheological properties (self-healing, shear-thinning), antimicrobial activity (antibacterial and antifungal assays), and biocompatibility (cytotoxicity against mammalian cells).","limitations":"In vitro study only — no animal wound healing data. The specific antimicrobial spectrum and potency (minimum inhibitory concentrations) aren't detailed in the abstract. Long-term stability and degradation of the hydrogel in a wound environment are unknown. Manufacturing scale-up not addressed."},{"rthcId":"RPEP-09528","title":"Suppressed thyroid stimulating hormone levels after initiation of a subcutaneous glucagon-like peptide-1 receptor agonist in a post-thyroidectomy patient managed with levothyroxine case report.","authors":"Wilcox, Lauren; Van Dril, Elizabeth","year":2024,"journal":"Journal of the American Pharmacists Association : JAPhA, 64(6), 102185","doi":"10.1016/j.japh.2024.102185","pmid":"38992739","tags":["glp-1-agonists","thyroid-health"],"studyType":"case series","evidenceStrength":"preliminary","keyFinding":"Subcutaneous semaglutide initiation caused TSH suppression in a post-thyroidectomy patient on stable levothyroxine replacement, necessitating a 25% levothyroxine dose reduction after 5 years of stable dosing.","whyItMatters":"Millions of people take both levothyroxine and GLP-1 drugs. If semaglutide alters thyroid hormone requirements — whether through weight loss, absorption changes, or direct effects — patients on thyroid replacement need closer monitoring to avoid hyperthyroid symptoms or osteoporosis risk from excess thyroid hormone.","specificNumbers":"Single patient case — TSH suppressed after GLP-1 RA initiation in a patient previously stable on levothyroxine after thyroidectomy.","methodology":"Single case report documenting the temporal relationship between semaglutide initiation/titration and TSH suppression in a post-thyroidectomy patient. Thyroid function tests and levothyroxine dosing history were reviewed.","limitations":"Single case report — cannot establish causation. The TSH change could be coincidental or multifactorial. The relative contribution of weight loss versus absorption changes versus direct GLP-1 effects cannot be distinguished. No population-level data to estimate how common this interaction is."},{"rthcId":"RPEP-09529","title":"Role of innate host defense proteins in oral cancerogenesis.","authors":"Winter, Jochen; Jepsen, Søren","year":2024,"journal":"Periodontology 2000, 96(1), 203-220","doi":"10.1111/prd.12552","pmid":"38265172","tags":["antimicrobial-peptides","cancer-research","immune-function"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Antimicrobial polypeptides LL-37 and human defensins, along with S100 proteins and alarmins, can promote oral tumorigenesis through direct growth receptor binding and indirect tumor-promoting gene induction, potentially linking chronic periodontitis to oral squamous cell carcinoma.","whyItMatters":"Periodontitis affects nearly half of adults and oral cancer is the most common oral malignancy. Understanding that the body's own antimicrobial peptides — meant to fight infection — can inadvertently promote cancer reveals a molecular mechanism linking these two diseases and could lead to new prevention strategies.","specificNumbers":"Periodontitis is highly prevalent and oral squamous cell carcinomas are the most common oral malignant lesions.","methodology":"Narrative review synthesizing evidence on how innate host defense molecules (cathelicidin LL-37, defensins, S100 proteins, alarmins) participate in oral cancer development in the context of chronic periodontal inflammation.","limitations":"Review article without new experimental data. The causal links between AMP elevation, periodontitis, and oral cancer are largely associative and mechanistically plausible rather than definitively proven in humans. Individual AMP contributions are difficult to isolate in the complex oral inflammatory environment."},{"rthcId":"RPEP-09530","title":"Small Spleen Peptides (SSPs) Shape Dendritic Cell Differentiation through Modulation of Extracellular ATP Synthesis Profile.","authors":"Wixler, Viktor; Leite Dantas, Rafael; Varga, Georg; Boergeling, Yvonne; Ludwig, Stephan","year":2024,"journal":"Biomolecules, 14(4)","doi":"10.3390/biom14040469","pmid":"38672485","tags":["bioactive-peptides","immune-function","autoimmune-conditions"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Small spleen peptides (thymosins/Tβ4) transform dendritic cells into tolerogenic cells by modulating extracellular ATP synthesis and degradation profiles, with the adenosine receptor mediating the tolerogenic phenotype, and in vivo administration inhibits psoriatic skin inflammation.","whyItMatters":"Current autoimmune treatments often broadly suppress the immune system, increasing infection risk. These spleen-derived peptides offer a more elegant approach — reprogramming specific immune cells toward tolerance rather than blanket suppression. If developed therapeutically, they could treat autoimmune diseases with fewer side effects.","specificNumbers":"SSPs maintained tolerogenic DC function even in the presence of pro-inflammatory TNFα. Regulatory T cell induction was confirmed.","methodology":"SSP composition was analyzed (thymosins identified as primary constituents). Real-time extracellular ATP levels were measured in dendritic cells under tolerogenic vs. immunogenic stimulation. Recombinant thymosin peptides were compared to SSPs for arthritis inhibition. Adenosine receptor involvement was tested pharmacologically. In vivo efficacy assessed in psoriatic skin inflammation model.","limitations":"The natural SSP extract outperformed recombinant peptides, suggesting unknown synergistic components — making therapeutic development more complex. Mouse models of psoriasis don't perfectly replicate human disease. The specific thymosin peptides and their optimal ratios for therapeutic effect are not yet defined. Long-term effects of tolerance induction not assessed."},{"rthcId":"RPEP-09531","title":"Pharmacokinetics of collagen dipeptides (Gly-Pro and Pro-Hyp) and tripeptides (Gly-Pro-Hyp) in rats.","authors":"Won, Jihyun; Kang, Juhyung; Noh, Keumhan; Chung, Hee-Chul; Kang, Wonku","year":2024,"journal":"Journal of food science, 89(1), 701-709","doi":"10.1111/1750-3841.16871","pmid":"38051020","tags":["collagen-peptides","drug-delivery"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"First individual PK profiling of collagen peptides shows Gly-Pro-Hyp has 4.4% oral bioavailability and Pro-Hyp has 19.3%, with flip-flop kinetics indicating transporter-mediated absorption and double-peak patterns suggesting multiple absorption sites.","whyItMatters":"Millions of people take collagen supplements, but the fundamental question of how much actually reaches the bloodstream was unanswered until now. This study provides the first rigorous pharmacokinetic data for individual collagen peptides, showing that absorption is low and peptide-specific — information essential for rational dosing.","specificNumbers":"IV dose: 5 mg/kg. Oral dose: 100 mg/kg. Oral bioavailability ranged from ~18% to ~39%. Pro-Hyp showed highest absorption.","methodology":"Rats received individual collagen peptides (Gly-Pro-Hyp, Pro-Hyp, Gly-Pro) via IV (5 mg/kg) and intragastric (100 mg/kg) routes. Plasma levels and urinary excretion were measured by LC-MS/MS. Pharmacokinetic parameters including absolute oral bioavailability, Cmax, Tmax, and elimination rates were calculated.","limitations":"Rat pharmacokinetics — human absorption may differ significantly due to differences in gut transporters, pH, and transit time. Individual peptides were given in isolation, while collagen supplements contain complex mixtures where peptides may compete for transporters. The doses used (100 mg/kg oral) are high relative to typical human supplement doses. The biological significance of the small absorbed fraction is not addressed."},{"rthcId":"RPEP-09532","title":"Central glucagon-like peptide 1 receptor activation inhibits Toll-like receptor agonist-induced inflammation.","authors":"Wong, Chi Kin; McLean, Brent A; Baggio, Laurie L; Koehler, Jacqueline A; Hammoud, Rola; Rittig, Nikolaj; Yabut, Julian M; Seeley, Randy J; Brown, Theodore J; Drucker, Daniel J","year":2024,"journal":"Cell metabolism, 36(1), 130-143.e5","doi":"10.1016/j.cmet.2023.11.009","pmid":"38113888","tags":["glp-1-agonists","inflammation","neurological-conditions"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"GLP-1R activation attenuates TLR agonist-induced TNF-α through central neuronal GLP-1Rs (not hematopoietic or endothelial), requiring α1-adrenergic, δ-opioid, and κ-opioid receptor signaling, and protects against polymicrobial sepsis through the same neuronal pathway.","whyItMatters":"This fundamentally changes our understanding of how GLP-1 drugs reduce inflammation — they work through the brain, not the immune system. This 'gut-brain-immune' axis could explain why GLP-1 drugs reduce cardiovascular events, and opens the door to new anti-inflammatory strategies that leverage brain-immune communication.","specificNumbers":"GLP-1R activation attenuated plasma TNFα and other inflammatory markers in response to TLR agonists. Central blockade eliminated the anti-inflammatory effect.","methodology":"Multiple TLR agonists were used to induce inflammation. Bone marrow chimeras determined whether GLP-1R effects were hematopoietic vs. non-hematopoietic. Neuronal GLP-1R requirement was tested with neuronal-specific knockouts. Pharmacological antagonists identified downstream adrenergic and opioid receptor involvement. Efficacy was validated in a cecal slurry polymicrobial sepsis model.","limitations":"Mouse study — human brain-immune circuits may differ. The relative contribution of this neuronal pathway versus other GLP-1R-mediated anti-inflammatory mechanisms in clinical settings is unknown. The specific brain regions mediating the effect are not fully mapped. Whether this mechanism contributes to the cardiovascular benefits seen in GLP-1 drug clinical trials remains speculative."},{"rthcId":"RPEP-09533","title":"A Modified Cell-Penetrating Peptide Enhances Insulin and Oxytocin Delivery across an RPMI 2650 Nasal Epithelial Cell Barrier In Vitro.","authors":"Wong, Sara; Brown, Alexander D; Abrahams, Abigail B; Nurzak, An Nisaa; Eltaher, Hoda M; Sykes, David A; Veprintsev, Dmitry B; Fone, Kevin C F; Dixon, James E; King, Madeleine V","year":2024,"journal":"Pharmaceutics, 16(10)","doi":"10.3390/pharmaceutics16101267","pmid":"39458599","tags":["insulin","oxytocin","drug-delivery"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"PLR enhanced insulin transcytosis across RPMI 2650 human nasal epithelial cells by 7.8-fold at 2:1 insulin/PLR molar ratio (p<0.05), with each PLR domain (membrane docking, uptake, endosomal escape) contributing to the enhancement.","whyItMatters":"Needle-free delivery of peptide drugs would be transformative — especially for insulin, which currently requires injection for systemic delivery. Nasal delivery also offers a direct route to the brain, which could benefit oxytocin-based therapies for neuropsychiatric conditions. PLR's ability to enhance transport without cellular damage makes it a practical delivery platform.","specificNumbers":"GET system enhanced transport of both insulin and oxytocin across nasal epithelial barriers compared to unassisted controls.","methodology":"RPMI 2650 human nasal epithelial cells cultured at air-liquid interface served as a nasal barrier model. PLR (P21-LK15-8R, 44 residues) was tested with insulin (51 residues, negative charge) and oxytocin (9 residues, positive charge) at various molar ratios. Transcytosis was measured over 6 hours. Individual PLR domains were tested to establish structure-function relationships.","limitations":"In vitro only — the RPMI 2650 cell model doesn't fully replicate the human nasal environment (mucus, mucociliary clearance, enzymes). The 7.8-fold enhancement is relative to baseline, and absolute transport percentages aren't provided. No in vivo nasal delivery data. Ciliotoxicity and long-term safety not assessed. Oxytocin enhancement was less impressive, suggesting the approach is cargo-dependent."},{"rthcId":"RPEP-09534","title":"Impact of GLP-1 Receptor Agonist Use in Patients With Steatotic Liver Disease and Type 2 Diabetes: A Retrospective Cohort Study.","authors":"Wood, Marci; Kennedy, Amanda G; Khan, Sidra; Hitt, Juvena R; Davis, Kayla; Reddy, Sheela S; Gilbert, Matthew P","year":2024,"journal":"Journal of pharmacy practice, 37(6), 1297-1302","doi":"10.1177/08971900241253661","pmid":"38720191","tags":["glp-1-agonists","metabolic-health","liver-health"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Patients treated with GLP-1 RAs showed less liver fibrosis progression (by FIB-4 score) compared to untreated controls in a retrospective cohort of 242 T2DM patients with steatotic liver disease, though differences were modest.","whyItMatters":"Fatty liver disease affects roughly 25% of the global population and is even more common in diabetes. Few approved treatments exist for liver fibrosis. If GLP-1 drugs — already widely used for diabetes — also slow liver scarring, it provides a compelling additional reason to choose them as first-line diabetes therapy in patients with fatty liver disease.","specificNumbers":"Retrospective study period: January to December 2021. Compared GLP-1 RA users to non-users among patients with T2DM and NAFLD/NAFL/NASH.","methodology":"Retrospective cohort study of adult patients with T2DM and NAFLD/NAFL/NASH (Jan-Dec 2021). Excluded: hepatitis B/C, pioglitazone use. 79 GLP-1 RA users compared to 163 controls. Primary outcome: change in FIB-4 score. Secondary: NAFLD Fibrosis Score (NFS). Follow-up labs 3-15 months after baseline.","limitations":"Retrospective, non-randomized design — patients who received GLP-1 RAs may differ systematically from controls. Small sample size and short follow-up (3-15 months). FIB-4 is an indirect surrogate for fibrosis, not direct liver biopsy measurement. The baseline GLP-1 RA group had higher NFS, suggesting potentially more advanced disease. Confounding by other medications, lifestyle changes, and weight loss not fully controlled."},{"rthcId":"RPEP-09535","title":"Identification of human host factors required for beta-defensin-2 expression in intestinal epithelial cells upon a bacterial challenge.","authors":"Wozniak, Weronika; Sechet, Emmanuel; Kwon, Yong-Jun; Aulner, Nathalie; Navarro, Lionel; Sperandio, Brice","year":2024,"journal":"Scientific reports, 14(1), 15442","doi":"10.1038/s41598-024-66568-y","pmid":"38965312","tags":["antimicrobial-peptides","gut-health","immune-function"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Whole-genome RNAi screen in intestinal epithelial cells identified 57 confirmed host factors controlling HBD2 expression upon bacterial challenge, including TLR5-MYD88 signaling, novel epigenetic regulators, and the IBD-associated transcription factor GATA6.","whyItMatters":"In an era of antibiotic resistance, boosting the body's own antimicrobial peptide production is an attractive therapeutic strategy. This study maps the complete regulatory network for intestinal defensin expression, revealing druggable targets — especially relevant for conditions like inflammatory bowel disease where defensin production is often impaired.","specificNumbers":"Multiple host factors identified as required for beta-defensin-2 expression in response to bacterial challenge.","methodology":"Genome-wide siRNA screen in human intestinal epithelial cells challenged with bacteria. Duplicate screening identified 79 genes promoting and 110 genes inhibiting HBD2 expression. 57 hits were confirmed through counter-screening and validation, with functional characterization of selected factors.","limitations":"In vitro screen using immortalized intestinal epithelial cells — may not fully capture the complexity of defensin regulation in the intact gut with its multiple cell types, microbiome, and immune system interactions. siRNA knockdown may have off-target effects. Validation was performed on a subset of hits."},{"rthcId":"RPEP-09536","title":"Initiating GLP-1 Therapy in Combination with FreeStyle Libre Provides Greater Benefit Compared with GLP-1 Therapy Alone.","authors":"Wright, Eugene E; Roberts, Gregory J; Chuang, Joyce S; Nabutovsky, Yelena; Virdi, Naunihal; Miller, Eden","year":2024,"journal":"Diabetes technology & therapeutics, 26(10), 754-762","doi":"10.1089/dia.2024.0015","pmid":"38669474","tags":["glp-1-agonists","metabolic-health"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Initiating GLP-1 RA therapy with FreeStyle Libre produced 0.70% greater HbA1c reduction at 6 months compared to GLP-1 RA alone in matched cohorts (-2.43% vs. -1.73%, p<0.001) among adults with T2D and baseline HbA1c ≥8%.","whyItMatters":"This suggests that combining drug therapy with glucose monitoring technology produces better outcomes than either alone. For the millions starting GLP-1 drugs, adding a CGM could substantially amplify their benefits — potentially reducing diabetes complications and healthcare costs.","specificNumbers":"Significant additional HbA1c reduction in the GLP-1+FSL group versus GLP-1-only group, measured from real-world electronic health records.","methodology":"Real-world retrospective cohort using Optum's Market Clarity linked EHR-claims database (2018-2022). Adults with T2D and HbA1c ≥8% starting first GLP-1 RA. GLP-1+FSL group (n=478) acquired FSL within ±30 days of first GLP-1. 1:5 matched to GLP-1-only controls (n=2,390) on insulin therapy, age, sex, baseline HbA1c, and GLP-1 type. HbA1c change at 6 months.","limitations":"Retrospective observational design — patients who adopt both GLP-1 and CGM may be more health-motivated than those choosing only one. Selection bias cannot be fully eliminated by matching. The study captures only 6-month outcomes. The mechanism of benefit (behavioral change from CGM data) is assumed but not measured. Only FreeStyle Libre was studied — other CGM systems may differ."},{"rthcId":"RPEP-09537","title":"The first bioactive (angiotensin-converting enzyme-inhibitory) peptide isolated from pearl matrix protein.","authors":"Wu, Chaoyi; Yin, Zehui; Wang, Yayu; Chen, Xinjiani; Li, Bailei; Wang, Qin; Yao, Liping; Zhang, Zhen; Liu, Xiaojun; Zhang, Rongqing","year":2024,"journal":"Heliyon, 10(7), e28060","doi":"10.1016/j.heliyon.2024.e28060","pmid":"38560194","tags":["bioactive-peptides","cardiovascular-health"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"KKCHFWPFPW (MW 1417.5 Da, pI 9.31) from Pinctada fucata pearl matrix competitively inhibits ACE with IC50 of 4.17 μM, confirmed by Lineweaver-Burk plot analysis and molecular docking simulations.","whyItMatters":"This discovery adds pearls to the growing list of unexpected natural sources of bioactive peptides. While the practical applications are still far off, it demonstrates that traditional remedies sometimes contain genuine pharmacological compounds waiting to be discovered with modern analytical tools.","specificNumbers":"Peptide KKCHFWPFPW: molecular weight 1417.5 Da, isoelectric point 9.31. First ACE-inhibiting peptide from pearl matrix.","methodology":"Pearl matrix protein from Pinctada fucata was processed and peptides identified by quadrupole time-of-flight mass spectrometry. ACE inhibition was quantified by HPLC (IC50 determination). Inhibition kinetics analyzed by Lineweaver-Burk plots. Molecular docking simulations (Maestro 2022-1 Glide) characterized the peptide-ACE binding interaction.","limitations":"In vitro study only — no evidence the peptide survives digestion or reaches the bloodstream. The IC50 of 4.17 μM is moderate compared to pharmaceutical ACE inhibitors. Pearl protein is not a practical food source for most people. The molecular docking is computational prediction, not experimentally confirmed binding. No cell or animal studies."},{"rthcId":"RPEP-09538","title":"Personalized neoantigen cancer vaccines: current progression, challenges and a bright future.","authors":"Wu, Da-Wei; Jia, Shuo-Peng; Xing, Shu-Jun; Ma, Hai-Lan; Wang, Xin; Tang, Qi-Yu; Li, Zi-Wei; Wu, Qing; Bai, Min; Zhang, Xin-Yong; Fu, Xiao-Feng; Jia, Ming-Ming; Tang, Yu; Chen, Li; Li, Ning","year":2024,"journal":"Clinical and experimental medicine, 24(1), 229","doi":"10.1007/s10238-024-01436-7","pmid":"39325256","tags":["bioactive-peptides","cancer-research","immune-function"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Of 199 neoantigen vaccine clinical trials, peptide vaccines dominate (64.8%), delivery platforms are shifting toward DC systems (16.1%) and LNP/LPX (11%), most trials are Phase I (59.8%), and combination with immune checkpoint inhibitors is the primary development strategy.","whyItMatters":"Personalized cancer vaccines represent one of the most promising frontiers in oncology — targeting each patient's unique tumor mutations. This comprehensive landscape analysis helps researchers, investors, and patients understand where the field stands and where it's heading.","specificNumbers":"Review covers clinical trials globally from the Trialtrove database, spanning multiple vaccine platforms and cancer types.","methodology":"Retrospective analysis of the Trialtrove database for all personalized neoantigen vaccine clinical trials initiated through December 2022. Analyzed by phase, sponsor type, host country, treatment modality, combination strategy, delivery platform, and cancer type.","limitations":"Database analysis can't assess trial quality or results — only counts and characteristics. Many trials are early-phase with unknown outcomes. The rapid pace of the field means the landscape may have changed significantly since the December 2022 cutoff. Peptide vaccine dominance by count may not reflect clinical efficacy rankings."},{"rthcId":"RPEP-09539","title":"Validity of Plasma Neuropeptide Y in Combination with Clinical Factors in Predicting Neuralgia Following Herpes Zoster.","authors":"Wu, Dan; Li, Fang; Yang, Feifei; Liu, Jun","year":2024,"journal":"International journal of general medicine, 17, 4805-4814","doi":"10.2147/IJGM.S480411","pmid":"39440102","tags":["neuropeptides","pain-management","neurological-conditions"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Low plasma NPY levels independently predicted PHN development in 182 herpes zoster patients, and combining NPY with clinical factors (age, pain severity, rash area) improved predictive accuracy from AUC 0.804 to 0.873.","whyItMatters":"PHN causes chronic debilitating pain that's extremely difficult to treat once established. Being able to predict which shingles patients will develop PHN could allow doctors to intervene early with aggressive pain management and potentially prevent the condition from becoming chronic.","specificNumbers":"182 patients studied between February 2022 and December 2023. Plasma NPY combined with clinical factors for prediction model.","methodology":"Prospective cohort study (Feb 2022-Dec 2023). 182 herpes zoster patients and 38 healthy controls. NPY, BDNF, and NGF measured within 3 days of healing. 59 patients developed PHN. Logistic regression identified independent predictors. AUC analysis compared clinical factors alone vs. combined with NPY levels.","limitations":"Single-center study with moderate sample size (182 patients). NPY levels were measured at one time point — serial measurements might improve prediction. The optimal NPY cutoff for clinical decision-making is not established. Other biomarkers beyond NPY, BDNF, and NGF may also contribute to prediction. Whether early intervention guided by NPY testing actually prevents PHN requires a separate interventional study."},{"rthcId":"RPEP-09540","title":"Association of glucagon-like peptide receptor 1 agonist therapy with the presence of gastric contents in fasting patients undergoing endoscopy under anesthesia care: a historical cohort study.","authors":"Wu, Fei; Smith, Matthew R; Mueller, Ariel L; Klapman, Seth A; Everett, Lucinda L; Houle, Timothy; Kuo, Braden; Hobai, Ion A","year":2024,"journal":"Canadian journal of anaesthesia = Journal canadien d'anesthesie, 71(7), 958-966","doi":"10.1007/s12630-024-02719-z","pmid":"38485835","tags":["glp-1-agonists","gut-health"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"GLP-1 agonist therapy was associated with an adjusted odds ratio of 5.8 (95% CI 1.7-19.3, p=0.004) for residual gastric contents in fasting patients, with 19% of GLP-1 users showing visible food at endoscopy versus 5% of controls.","whyItMatters":"With millions of people now taking GLP-1 drugs, this is a critical safety signal for anesthesia and procedural medicine. Retained gastric contents during sedation can lead to aspiration pneumonia — a potentially fatal complication. Patients and providers need to be aware that standard fasting guidelines may not be sufficient for GLP-1 drug users.","specificNumbers":"90 procedures in GLP-1 users compared to matched controls. Study period: 2019-2023.","methodology":"Historical cohort study reviewing EGD records (2019-2023). 90 procedures in patients on GLP-1 agonists (GLP group) compared to 102 procedures in patients who started GLP-1 therapy within 1,000 days after their EGD (control). Excluded: emergent procedures, combined EGD/colonoscopy, known gastroparesis, previous gastric surgery. Confounder-adjusted generalized linear mixed effect model.","limitations":"Retrospective design with relatively small sample sizes. The control group (future GLP-1 users) may differ from the GLP group in ways that affect gastric emptying. Documentation of gastric contents may vary by endoscopist. The fasting duration was comparable but specific timing of last GLP-1 dose was not captured. The study cannot establish how long before a procedure GLP-1 drugs should be held."},{"rthcId":"RPEP-09541","title":"Development of a synthetic relaxin-3/INSL5 chimeric peptide ligand for NanoBiT complementation binding assays.","authors":"Wu, Hongkang; Hoare, Bradley L; Handley, Thomas N G; Akhter Hossain, Mohammed; Bathgate, Ross A D","year":2024,"journal":"Biochemical pharmacology, 224, 116238","doi":"10.1016/j.bcp.2024.116238","pmid":"38677442","tags":["relaxin","gut-health","neurological-conditions"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"SmBiT-conjugated R3/I5 chimeric peptide binds LgBiT-RXFP3 and LgBiT-RXFP4 with nanomolar affinity and minimal non-specific binding, enabling robust saturation and competition binding assays from whole cells and frozen membranes without ligand separation.","whyItMatters":"Drug discovery for RXFP3 (anxiety, eating disorders) and RXFP4 (irritable bowel, colonic dysmotility) has been stalled by inadequate tools. This assay system removes a major bottleneck, enabling high-throughput screening that could accelerate the development of new treatments for these conditions.","specificNumbers":"Chimeric peptide designed to interact with both RXFP3 (brain/anxiety) and RXFP4 (gut/motility) receptors.","methodology":"Solid-phase peptide synthesis of R3/I5 chimeric peptide and SmBiT-PEG12-R3/I5 conjugate. Stable HEK293T cell lines expressing LgBiT-RXFP3 and LgBiT-RXFP4 were generated and validated for signaling. NanoBiT complementation binding assays were optimized for kinetic, saturation, and competition binding in whole-cell and membrane formats.","limitations":"The assay system was developed and validated in HEK293T cells overexpressing tagged receptors — binding characteristics may differ in native tissues. The R3/I5 chimeric peptide activates both RXFP3 and RXFP4, so receptor-specific selectivity must come from the test compounds, not the tracer. In vivo validation of compounds identified through this screen remains necessary."},{"rthcId":"RPEP-09542","title":"Lactoferricin, an antimicrobial motif derived from lactoferrin with food preservation potential.","authors":"Wu, Jiajia; Zang, Mingwu; Wang, Shouwei; Qiao, Xiaoling; Zhao, Bing; Bai, Jing; Zhao, Yan; Shi, Yuxuan","year":2024,"journal":"Critical reviews in food science and nutrition, 64(25), 9032-9044","doi":"10.1080/10408398.2023.2207650","pmid":"37158176","tags":["lactoferrin","antimicrobial-peptides"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"43 new lactoferricin variants were identified from mammalian lactoferrins across six taxonomic families (Primates, Rodentia, Artiodactyla, Perissodactyla, Pholidota, Carnivora), expanding the known LFcin family and its food preservation potential.","whyItMatters":"Antimicrobial resistance and consumer demand for natural food preservatives are both driving the search for new antimicrobial solutions. Lactoferricins — natural peptides from milk — could address both needs: fighting drug-resistant pathogens while serving as clean-label food preservatives.","specificNumbers":"LFcin shows significantly better antimicrobial activity than its parent protein lactoferrin across a variety of bacteria and fungi.","methodology":"Sequence and structural similarity searches of protein databases to identify novel lactoferricin sequences from mammalian lactoferrins. Comprehensive review of LFcin sequences, structures, antimicrobial activities, structural/functional motifs, and food preservation applications.","limitations":"Bioinformatic identification of new variants requires experimental validation of antimicrobial activity. Most food preservation studies use bovine or human LFcin — the other 43 variants are largely uncharacterized. Practical challenges like peptide stability in food matrices, cost of production, and regulatory approval for food use are not addressed in detail."},{"rthcId":"RPEP-09543","title":"Cell-penetrating peptides for transmucosal delivery of proteins.","authors":"Wu, Jiamin; Roesger, Sophie; Jones, Natalie; Hu, Che-Ming J; Li, Shyh-Dar","year":2024,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 366, 864-878","doi":"10.1016/j.jconrel.2024.01.038","pmid":"38272399","tags":["bioactive-peptides","drug-delivery","peptide-chemistry"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"CPPs are a versatile platform for enhancing protein permeation across multiple mucosal barriers, with route-specific optimization needed to address the distinct structural and physicochemical challenges of nasal, buccal, sublingual, and oral mucosa.","whyItMatters":"Eliminating the need for injections would transform how protein drugs are delivered — improving patient comfort, compliance, and accessibility. CPPs represent one of the most promising approaches to achieve this, and understanding which routes work best for which drugs is critical for advancing the technology.","specificNumbers":"Review covers four mucosal routes (nasal, buccal, sublingual, oral) and their distinct barrier properties affecting CPP-mediated delivery.","methodology":"Comprehensive review examining the structural and physicochemical attributes of nasal, buccal, sublingual, and oral mucosal barriers, recent CPP development for protein delivery across each barrier, and challenges for clinical translation.","limitations":"Review article — no new experimental data. CPP-mediated delivery faces significant challenges including peptide stability, formulation complexity, dose variability, and the gap between in vitro and in vivo performance. Regulatory pathways for CPP-drug conjugates are still undefined. Safety concerns about chronic mucosal exposure to CPPs are not fully resolved."},{"rthcId":"RPEP-09544","title":"A General and Convenient Peptide Self-Assembling Mechanism for Developing Supramolecular Versatile Nanomaterials Based on The Biosynthetic Hybrid Amyloid-Resilin Protein.","authors":"Wu, Junjun; Zhou, Lin; Peng, Hu; Wang, Zhaojun; Wang, Zhaoshi; Keasling, Jay D; Liu, Shike; Zhou, Guanghong; Ding, Shijie; Wang, Qiong; Wang, Xuejian; Chen, Xinxiu; Lang, Yifei; Xia, Mo; Guan, Xin; Dong, Mingsheng; Zhou, Jingwen; Chen, Jian","year":2024,"journal":"Advanced materials (Deerfield Beach, Fla.), 36(4), e2304364","doi":"10.1002/adma.202304364","pmid":"37885340","tags":["bioactive-peptides","peptide-chemistry"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Ure2 amyloidogenic peptide-resilin hybrid proteins self-assemble into supramolecular hydrogels with simultaneous wet adhesion, self-healing, rapid gelation, cell growth promotion, and hemostasis, outperforming commercial counterparts in tissue engineering and wound healing applications.","whyItMatters":"Most biomaterials excel at one property but sacrifice others. This single-protein material breaks that trade-off by combining structural order (amyloid) with disorder (resilin), creating a material that could simplify wound care, tissue engineering, and surgical applications — with one material replacing multiple commercial products.","specificNumbers":"The strategy worked with multiple diverse proteins, each retaining function within the hydrogel network.","methodology":"Biosynthetic hybrid proteins combining Ure2 amyloidogenic peptide sequences with resilin elastomeric polypeptide were expressed, purified, and characterized for self-assembly behavior, mechanical properties, adhesion, self-healing, and biological activity. Performance was tested in vitro (cell adhesion, proliferation, differentiation) and in vivo (tissue engineering, cosmetic, hemostasis applications).","limitations":"Long-term biocompatibility and degradation in vivo need further study. Manufacturing scale-up of biosynthetic proteins may be challenging and costly. The comparison to commercial products may not reflect all clinical scenarios. Regulatory approval pathway for a novel protein biomaterial would be lengthy."},{"rthcId":"RPEP-09545","title":"Semaglutide May Ameliorate Fibrosis and Inhibit Epithelial-Mesenchymal Transition in Intrauterine Adhesion Models.","authors":"Wu, Luming; Zhan, Yue; Wang, Yiqing","year":2024,"journal":"International journal of molecular sciences, 25(11)","doi":"10.3390/ijms25116196","pmid":"38892384","tags":["semaglutide","glp-1-agonists"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Semaglutide significantly reduced fibrosis markers (ACTA2, COL1A1, FN), inflammatory cytokines (TNF-α, IL-6, NF-κB), and epithelial-mesenchymal transition markers (vimentin, E-cadherin, N-cadherin) in both TGF-β1-induced endometrial cell and surgically-induced mouse models of intrauterine adhesions.","whyItMatters":"Intrauterine adhesions affect an estimated 20% of women who undergo uterine procedures. Finding that a widely available, well-characterized drug like semaglutide has anti-fibrotic and anti-inflammatory effects in the uterus could provide a new treatment option for a condition with limited therapeutic choices.","specificNumbers":"Three semaglutide dose levels tested in animal models. Cell models showed dose-dependent effects on EMT markers after 48-hour treatment.","methodology":"In vitro: human endometrial epithelial cells were stimulated with TGF-β1 and co-cultured with different semaglutide concentrations for 48h. In vivo: IUA was induced in mice by mechanical curettage plus inflammatory stimulation; three semaglutide doses were injected subcutaneously daily for 2 weeks. RT-qPCR, Western blotting, HE staining, Masson staining, and ELISA were used for analysis.","limitations":"Preclinical study — no human clinical data for IUA treatment with semaglutide. The mouse IUA model doesn't perfectly replicate human disease. Daily SC injection for 2 weeks is a short treatment period. GLP-1 receptor expression in human endometrial tissue needs confirmation. Fertility outcomes were not assessed."},{"rthcId":"RPEP-09546","title":"A β-Lactamase Responsive Peptide Inhibits MRSA Infection through Self-Assembled Nanonet.","authors":"Wu, Minghao; Li, Yuting; Shen, Huaxing; Zhang, Yanan; Cong, Wei; Hu, Xiaochun; Shi, Yejiao; Hu, Honggang","year":2024,"journal":"Advanced healthcare materials, 13(31), e2402453","doi":"10.1002/adhm.202402453","pmid":"39118587","tags":["antimicrobial-peptides","drug-delivery"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"BLAP responds specifically to MRSA-secreted β-lactamase by assembling in situ into nanofibrous networks that physically trap the bacteria, preventing host cell invasion and significantly reducing infection and abscess formation in mice.","whyItMatters":"MRSA kills tens of thousands of people annually and is resistant to nearly all β-lactam antibiotics. By using the very enzyme that confers resistance as the trigger for a bacteria-trapping mechanism, this approach turns MRSA's greatest strength into its downfall — a fundamentally new strategy for combating drug-resistant infections.","specificNumbers":"BLAP specifically activated by β-lactamase secreted by MRSA, forming nanonets that trapped and killed drug-resistant bacteria.","methodology":"BLAP was designed with a self-assembling peptide sequence responsive to β-lactamase cleavage, inspired by human defensin-6's nanonet formation. In vitro testing confirmed β-lactamase-triggered assembly, nanonet formation around MRSA, and prevention of host cell invasion. In vivo efficacy was tested by intramuscular BLAP injection in mice with MRSA infection.","limitations":"Early-stage preclinical study — efficacy in humans is unproven. BLAP works by physically trapping bacteria rather than killing them, so it may need to be combined with immune clearance or other antimicrobials. Not all MRSA strains produce the same levels of β-lactamase. Manufacturing and stability of the peptide for clinical use not addressed. Only tested against one bacterial species."},{"rthcId":"RPEP-09547","title":"Screening and molecular dynamics simulation of ACE inhibitory tripeptides derived from milk fermented with Lactobacillus delbrueckii QS306.","authors":"Wu, Nan; Li, Puyu; Shuang, Quan; Wuhanqimuge","year":2024,"journal":"Food & function, 15(5), 2655-2667","doi":"10.1039/d3fo03320a","pmid":"38362628","tags":["bioactive-peptides","cardiovascular-health"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Three ACE-inhibiting tripeptides (WRP IC50 46.7 μM, YRP IC50 89.6 μM, WSR IC50 300.1 μM) were identified from fermented milk, with molecular dynamics confirming stable enzyme binding for WRP.","whyItMatters":"Rather than just observing that fermented dairy lowers blood pressure, this study pinpoints the specific peptides responsible and maps exactly how they interact with ACE, opening the door to targeted functional food development.","specificNumbers":"WRP: IC50 46.707 μM. WSR: IC50 300.121 μM. YRP: IC50 89.555 μM. 16 stable tripeptides initially screened from fermented milk proteome.","methodology":"Proteomics identified peptides in fermented milk before and after ultra-high pressure treatment. Sixteen stable tripeptides were screened via activity prediction, PeptideCutter analysis, and hydrophobicity. ACE inhibition was tested in vitro; molecular dynamics simulation confirmed binding stability.","limitations":"This is an in vitro and computational study — it does not prove these peptides lower blood pressure in living organisms. Real-world bioavailability after full human digestion remains unconfirmed, and the peptide concentrations achievable through normal dairy consumption are unknown."},{"rthcId":"RPEP-09548","title":"Functionalized lipid nanoparticles modulate the blood-brain barrier and eliminate α-synuclein to repair dopamine neurons.","authors":"Wu, Xiaomei; Yuan, Renxiang; Xu, Yichong; Wang, Kai; Yuan, Hong; Meng, Tingting; Hu, Fuqiang","year":2024,"journal":"Asian journal of pharmaceutical sciences, 19(2), 100904","doi":"10.1016/j.ajps.2024.100904","pmid":"38601010","tags":["glp-1-agonists","exenatide","neurological-conditions","drug-delivery"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Borneol-functionalized lipid nanoparticles delivered exenatide across the BBB at 4.21× the rate of conventional LNPs, reducing α-synuclein to 51.85% and increasing dopamine to 1.85× in Parkinson's disease mice.","whyItMatters":"Parkinson's disease currently has no disease-modifying treatments — only symptom management. If exenatide can be reliably delivered to the brain via nanoparticles, it could become the first therapy to actually slow or halt disease progression.","specificNumbers":"Nanoparticles achieved brain penetration with BBB-targeting functions. α-synuclein was eliminated and dopamine neurons were repaired in Parkinson's mice.","methodology":"Researchers fabricated multi-functional LNPs with BBB-targeting, permeability-enhancing (borneol), and responsive-release functions. Tested in 15-month-old C57BL/6 Parkinson's model mice using immunofluorescence, behavioral testing, and immunohistochemistry.","limitations":"Mouse study only — the human blood-brain barrier is more restrictive, and mouse Parkinson's models don't fully replicate human disease complexity. Nanoparticle manufacturing scalability, long-term safety, and regulatory hurdles remain significant obstacles before clinical use."},{"rthcId":"RPEP-09549","title":"Efficacy and safety of GLP-1 receptor agonists combined with SGLT-2 inhibitors in elderly patients with type 2 diabetes: a meta-analysis.","authors":"Wu, Yaping; Yang, Zhenxing; Cao, Qingqing","year":2024,"journal":"American journal of translational research, 16(11), 6852-6866","doi":"10.62347/MCEE4840","pmid":"39678621","tags":["glp-1-agonists","metabolic-health"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"GLP-1RA + SGLT-2i combination therapy in elderly T2DM patients reduced HbA1c by an additional 0.26%, improved eGFR, lowered LDL by 0.56 mmol/L, raised HDL by 0.18 mmol/L, and reduced systolic BP by 3.15 mmHg — all without increased adverse events.","whyItMatters":"Elderly diabetes patients are typically underrepresented in clinical trials, yet they carry the highest cardiovascular and renal risk. This meta-analysis specifically confirms that the most promising modern drug combination works effectively and safely in this vulnerable population.","specificNumbers":"Meta-analysis of RCTs through May 2024 showing improvements in HbA1c, body weight, and blood pressure with the combination.","methodology":"Systematic review and meta-analysis of 15 randomized controlled trials (11,679 patients) from Web of Science, Cochrane Library, Embase, and PubMed through May 2024. Analyzed using RevMan 5.3 software.","limitations":"The definition of 'elderly' varied across included trials, and long-term outcomes beyond trial periods weren't assessed. The number of RCTs specifically targeting elderly populations remains limited. Individual drug combinations within the classes may differ in effect."},{"rthcId":"RPEP-09550","title":"Liraglutide, a glucagon-like peptide-1 receptor agonist, inhibits bone loss in an animal model of osteoporosis with or without diabetes.","authors":"Wu, Zongyi; Deng, Wei; Ye, Yiming; Xu, Jie; Han, Deyu; Zheng, Yu; Zheng, Qun","year":2024,"journal":"Frontiers in endocrinology, 15, 1378291","doi":"10.3389/fendo.2024.1378291","pmid":"38868747","tags":["liraglutide","glp-1-agonists","bone-health"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Across 17 animal studies, liraglutide improved bone imaging parameters, bone pathology, and bone maximum load while favorably altering bone metabolism markers, working through Wnt, AMPK/PGC1α, and OPG/RANKL/RANK pathways.","whyItMatters":"Osteoporosis and diabetes frequently coexist, especially in older adults. If liraglutide directly strengthens bone in addition to controlling blood sugar, it could become a dual-purpose treatment — and the bone benefits may extend to non-diabetic osteoporosis patients as well.","specificNumbers":"Improved bone mineral density, bone-related imaging parameters, and serum bone metabolism markers in both diabetic and non-diabetic osteoporosis models.","methodology":"Systematic review and meta-analysis of 17 animal studies from 8 databases (searched through April 2024). Risk of bias assessed using CAMARADES 10-item checklist; data analyzed with RevMan 5.3.","limitations":"All evidence comes from animal models — rodent bone biology differs from humans. Study quality was moderate (average 5.47/10), and many studies lacked blinding and sample size calculations. Human clinical trials specifically measuring bone outcomes with liraglutide are still needed."},{"rthcId":"RPEP-09551","title":"Experimental colonization with H. hepaticus, S. aureus and R. pneumotropicus does not influence the metabolic response to high-fat diet or incretin-analogues in wildtype SOPF mice.","authors":"Wunderlich, Margit; Miller, Manuel; Ritter, Bärbel; Le Gleut, Ronan; Marchi, Hannah; Majzoub-Altweck, Monir; Knerr, Patrick J; Douros, Jonathan D; Müller, Timo D; Brielmeier, Markus","year":2024,"journal":"Molecular metabolism, 87, 101992","doi":"10.1016/j.molmet.2024.101992","pmid":"39019114","tags":["glp-1-agonists","liraglutide","gut-health"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Colonization with H. hepaticus, S. aureus, and R. pneumotropicus did not alter HFD-induced body weight gain, food intake, body composition, glycemic control, or responsiveness to liraglutide or MAR709 in C57BL/6J mice.","whyItMatters":"This study validates the reliability of GLP-1 drug research conducted in pathogen-free mice. It removes a potential confounder that could have questioned whether positive preclinical results translate to real-world conditions where organisms naturally harbor infections.","specificNumbers":"Compared pathogen-colonized versus pathogen-free C57BL/6J mice. Tested both liraglutide and MAR709 (GLP-1/GIP co-agonist).","methodology":"Male C57BL/6J mice were experimentally infected with three common pathogens vs. specific-pathogen-free (SOPF) controls. Fed high-fat diet for 26 weeks, then treated daily for 6 days with liraglutide or MAR709. Body weight, food intake, body composition, and glycemic control compared.","limitations":"Only three specific pathogens were tested — this doesn't capture the full microbiome complexity of wild or 'dirty' mice. Only male mice were used. Drug treatment was only 6 days, which may not reveal long-term pathogen-drug interactions."},{"rthcId":"RPEP-09552","title":"Cathelicidin LL-37 promotes wound healing in diabetic mice by regulating TFEB-dependent autophagy.","authors":"Xi, Liuqing; Du, Juan; Xue, Wen; Shao, Kan; Jiang, Xiaohong; Peng, Wenfang; Li, Wenyi; Huang, Shan","year":2024,"journal":"Peptides, 175, 171183","doi":"10.1016/j.peptides.2024.171183","pmid":"38423213","tags":["ll-37-cathelicidin","antimicrobial-peptides","wound-healing"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"LL-37 accelerated diabetic wound healing by activating TFEB nuclear translocation, which upregulated autophagy markers ATG5, ATG7, and BECN1. Blocking autophagy or TFEB reversed LL-37's healing effects.","whyItMatters":"Diabetic wound healing is one of the most costly and common complications of diabetes, often leading to amputation. Understanding that LL-37 works through autophagy opens up new therapeutic approaches — either LL-37-based wound treatments or drugs that activate the same TFEB/autophagy pathway.","specificNumbers":"LL-37 activated TFEB and downstream autophagy markers. Blocking autophagy reduced LL-37's healing benefits in diabetic wound models.","methodology":"Full-thickness wound closure model in diabetic mice treated with LL-37 and/or autophagy inhibitor 3-MA. In vitro keratinocyte migration assays under high glucose conditions. TFEB activation measured by western blot and immunofluorescence; TFEB knockdown confirmed mechanism.","limitations":"Mouse study — diabetic mouse wounds differ from human chronic diabetic ulcers, which involve more complex vascular and neuropathic factors. The relative contribution of autophagy versus LL-37's antimicrobial and anti-inflammatory activities wasn't fully quantified."},{"rthcId":"RPEP-09553","title":"Tirzepatide's role in targeting adipose tissue macrophages to reduce obesity-related inflammation and improve insulin resistance.","authors":"Xia, Yin; Jin, Jing; Sun, Yaqin; Kong, Xiaocen; Shen, Ziyang; Yan, Rengna; Huang, Rong; Liu, Xiaomei; Xia, Wenqing; Ma, Jingjing; Zhu, Xudong; Li, Qian; Ma, Jianhua","year":2024,"journal":"International immunopharmacology, 143(Pt 2), 113499","doi":"10.1016/j.intimp.2024.113499","pmid":"39471690","tags":["tirzepatide","glp-1-agonists","inflammation","metabolic-health"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Tirzepatide (1.2 mg/kg twice weekly for 12 weeks) significantly reduced M1 adipose tissue macrophage infiltration, lowered inflammatory cytokines, and improved insulin sensitivity in obese mice through ERK pathway modulation and M1 macrophage apoptosis.","whyItMatters":"Fat tissue inflammation is increasingly recognized as the bridge between obesity and type 2 diabetes. If tirzepatide directly resolves this inflammation — rather than just causing weight loss — it addresses the root metabolic dysfunction, which could explain its remarkable clinical results.","specificNumbers":"Tirzepatide shifted ATM populations from M1 (inflammatory) to M2 (anti-inflammatory) phenotype with corresponding changes in cytokine profiles.","methodology":"High-fat diet-induced obese mouse models treated with tirzepatide 1.2 mg/kg twice weekly for 12 weeks. Assessed adipose tissue macrophage phenotype (M1/M2), inflammatory cytokine levels, ERK pathway activity, macrophage apoptosis, and insulin sensitivity markers.","limitations":"Mouse study — human adipose tissue inflammation is more complex. Difficult to separate the direct anti-inflammatory effects from indirect benefits of weight loss. The 12-week timeframe may not capture long-term immune adaptations."},{"rthcId":"RPEP-09554","title":"Antimicrobial Potential of Scorpion-Venom-Derived Peptides.","authors":"Xia, Zhiqiang; Xie, Lixia; Li, Bing; Lv, Xiangyun; Zhang, Hongzhou; Cao, Zhijian","year":2024,"journal":"Molecules (Basel, Switzerland), 29(21)","doi":"10.3390/molecules29215080","pmid":"39519721","tags":["antimicrobial-peptides","venom-derived-peptides"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Scorpion venom-derived peptides (both DBPs and NDBPs) demonstrate broad-spectrum antimicrobial activity against bacteria, fungi, and parasites, with rapid killing action and low propensity for resistance development.","whyItMatters":"Antibiotic resistance is projected to cause 10 million deaths annually by 2050. Scorpion venom peptides represent a largely untapped natural reservoir of antimicrobial compounds that work through fundamentally different mechanisms than conventional antibiotics, potentially bypassing existing resistance.","specificNumbers":"Review covers AMPs from multiple scorpion species with broad antibacterial spectrum and rapid action.","methodology":"Comprehensive literature review covering the molecular diversity, structural classification, antimicrobial mechanisms, and pharmaceutical potential of scorpion venom-derived antimicrobial peptides.","limitations":"Most scorpion venom antimicrobial peptides have only been studied in vitro. Major challenges remain for clinical development including toxicity to human cells, stability in the body, manufacturing costs, and delivery methods."},{"rthcId":"RPEP-09555","title":"Scorpion Venom Antimicrobial Peptide Derivative BmKn2-T5 Inhibits Enterovirus 71 in the Early Stages of the Viral Life Cycle In Vitro.","authors":"Xia, Zhiqiang; Wang, Huijuan; Chen, Weilie; Wang, Aili; Cao, Zhijian","year":2024,"journal":"Biomolecules, 14(5)","doi":"10.3390/biom14050545","pmid":"38785952","tags":["antimicrobial-peptides","venom-derived-peptides","immune-function"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"BmKn2-T5 inhibited EV71 dose-dependently in vitro, acting at early stages of the viral cycle. It also suppressed DENV, ZIKV, and HSV-1 replication, suggesting a shared early-stage viral target.","whyItMatters":"There is no approved antiviral for EV71, which causes significant childhood illness and occasional deaths. A peptide that blocks early viral entry could be developed into a broad-spectrum antiviral, potentially covering multiple unrelated viruses.","specificNumbers":"BmKn2-T5 inhibited EV71 when applied during early stages of infection in cell culture models.","methodology":"In vitro antiviral testing of BmKn2 and 5 derivatives against EV71 in cell cultures. Time-of-drug-addition experiments identified the affected viral life cycle stage. Cytotoxicity assessed. Cross-tested against dengue, Zika, and HSV-1.","limitations":"In vitro study only — cell culture antiviral activity doesn't guarantee effectiveness in animals or humans. The exact molecular target on the viruses hasn't been identified. Stability, delivery, and safety in vivo are unknown."},{"rthcId":"RPEP-09556","title":"Angiotensin-I-converting enzyme inhibitory peptides from eel (Anguilla japonica) bone collagen: preparation, identification, molecular docking, and protective function on HUVECs.","authors":"Xiang, Huan; Huang, Hui; Shao, Yanqiu; Hao, Shuxian; Li, Laihao; Wei, Ya; Chen, Shengjun; Zhao, Yongqiang","year":2024,"journal":"Frontiers in nutrition, 11, 1462656","doi":"10.3389/fnut.2024.1462656","pmid":"39703330","tags":["collagen-peptides","bioactive-peptides","cardiovascular-health"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Seven novel ACE inhibitory peptides were identified from eel bone collagen hydrolysates, with GPPGPPGL (IC50 535.84 μM) competitively binding ACE's S2 pocket. GPPGPPGL also increased nitric oxide and decreased endothelin-1 in HUVECs.","whyItMatters":"Finding ACE-inhibiting peptides that also promote blood vessel health offers dual cardiovascular benefits. Using eel bone waste as a source adds economic value to aquaculture byproducts while potentially creating functional food ingredients.","specificNumbers":"Multiple ACE-inhibiting peptide sequences identified from eel bone collagen. Molecular docking confirmed binding to ACE active site. HUVEC protection demonstrated against angiotensin II damage.","methodology":"Eel bone collagen hydrolyzed by alcalase and separated by ultrafiltration. 615 peptides identified via nano-HPLC-MS/MS; 7 ACE-inhibitory peptides screened through molecular docking. Kinetic analysis confirmed competitive inhibition. Vascular effects tested in HUVEC cell culture.","limitations":"In vitro study only — ACE inhibition in a test tube doesn't guarantee blood pressure lowering in humans. The IC50 of 535.84 μM is relatively high compared to pharmaceutical ACE inhibitors. Bioavailability after oral digestion is unknown."},{"rthcId":"RPEP-09557","title":"Two novel angiotensin I-converting enzyme inhibitory peptides from garlic protein: In silico screening, stability, antihypertensive effects in vivo and underlying mechanisms.","authors":"Xiang, Lu; Zheng, Zhenjia; Guo, Xiaojing; Bai, Ruoxi; Zhao, Renjie; Chen, Haihua; Qiu, Zhichang; Qiao, Xuguang","year":2024,"journal":"Food chemistry, 435, 137537","doi":"10.1016/j.foodchem.2023.137537","pmid":"37797452","tags":["bioactive-peptides","cardiovascular-health"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"MGR (IC50 4.50 μM) and HDCF (IC50 26.38 μM) from garlic protein competitively inhibited ACE, survived gastrointestinal digestion, and lowered blood pressure in spontaneously hypertensive rats through renin-angiotensin system modulation.","whyItMatters":"These are exceptionally potent food-derived ACE inhibitors — MGR's IC50 of 4.50 μM approaches pharmaceutical-grade potency. Combined with gastrointestinal stability and demonstrated in vivo efficacy, these garlic peptides are strong candidates for functional food development.","specificNumbers":"MGR: IC50 4.50 μM. HDCF: IC50 26.38 μM. Both competitive inhibitors. Both stable through simulated digestion. Both lowered blood pressure in SHR rats.","methodology":"In silico screening of garlic protein hydrolysates followed by ACE inhibition assays. Stability tested under heat, pH extremes, and simulated digestion. In vivo antihypertensive effects tested in spontaneously hypertensive rats with single and continuous dosing. Mechanisms explored via renin-angiotensin system, renal/cardiac pathology, and endothelial function markers.","limitations":"Animal study using spontaneously hypertensive rats, which don't perfectly model human hypertension. The doses used in rats may not translate directly to achievable concentrations from dietary garlic consumption. Human clinical trials are needed."},{"rthcId":"RPEP-09558","title":"Programming peptide-oligonucleotide nano-assembly for engineering of neoantigen vaccine with potent immunogenicity.","authors":"Xiang, Zhichu; Lu, Jianhua; Rao, Shangrui; Fu, Chenxing; Yao, Yuying; Yi, Yongdong; Ming, Yang; Sun, Weijian; Guo, Weisheng; Chen, Xiaoyuan","year":2024,"journal":"Theranostics, 14(6), 2290-2303","doi":"10.7150/thno.93395","pmid":"38646651","tags":["bioactive-peptides","cancer-research","immune-function"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Cationic module-programmed neoantigen peptides self-assembled with CpG into carrier-free nanoparticles that drove potent neoantigen-specific T-cell responses. Combined with anti-PD-1, they achieved significant inhibition or complete regression of melanoma and MC-38 colon tumors.","whyItMatters":"Personalized cancer vaccines are one of the most promising frontiers in immunotherapy, but manufacturing complexity limits their clinical adoption. A carrier-free system that self-assembles from simple peptide modification dramatically simplifies production while maintaining strong anti-tumor immunity.","specificNumbers":"Carrier-free nanoassembly platform co-delivered neoantigens and CpG adjuvant. Anti-tumor efficacy demonstrated in animal cancer models.","methodology":"Neoantigen peptides were N-terminally modified with a cationic module and co-assembled with CpG oligonucleotide. Nanoparticle formation, lymph node delivery, T-cell activation, and anti-tumor efficacy tested in mouse melanoma and MC-38 colon tumor models, alone and combined with anti-PD-1.","limitations":"Mouse study only — human immune responses to neoantigen vaccines can differ significantly. The self-assembly approach needs to be validated across diverse neoantigen sequences. Manufacturing scalability for personalized neoantigen identification and production hasn't been addressed."},{"rthcId":"RPEP-09559","title":"Bioactive peptides as a novel strategy to prevent alcoholic liver injury.","authors":"Xiao, Chuqiao; Li, Xiang-Guang; Zhao, Mouming","year":2024,"journal":"Advances in food and nutrition research, 110, 243-274","doi":"10.1016/bs.afnr.2024.04.003","pmid":"38906588","tags":["bioactive-peptides","liver-health"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Food-derived bioactive peptides from multiple protein sources demonstrate hepatoprotective activity against alcoholic liver injury through antioxidant, anti-inflammatory, and anti-apoptotic pathways in preclinical studies.","whyItMatters":"Alcoholic liver disease affects millions globally and has limited treatment options. Natural, food-derived peptides that protect liver cells could become safe dietary supplements or functional foods for at-risk populations.","specificNumbers":"Multiple food sources reviewed: milk, soy, fish, and other proteins. Multiple protective mechanisms identified.","methodology":"Comprehensive literature review covering bioactive peptide sources, preparation strategies (enzymatic hydrolysis), hepatoprotective mechanisms, and structure-activity relationships for liver protection against alcohol damage.","limitations":"Most evidence comes from in vitro and animal studies. No human clinical trials demonstrating that consuming these peptides prevents or treats alcoholic liver disease have been reported. The doses needed for liver protection may not be achievable through normal food consumption."},{"rthcId":"RPEP-09560","title":"Milk Exosome-Liposome Hybrid Vesicles with Self-Adapting Surface Properties Overcome the Sequential Absorption Barriers for Oral Delivery of Peptides.","authors":"Xiao, Peifu; Wang, Hanxun; Liu, Hongbing; Yuan, Haoyang; Guo, Chen; Feng, Yupeng; Qi, Pan; Yin, Tian; Zhang, Yu; He, Haibing; Tang, Xing; Gou, Jingxin","year":2024,"journal":"ACS nano, 18(32), 21091-21111","doi":"10.1021/acsnano.4c02560","pmid":"39099105","tags":["drug-delivery","bioactive-peptides"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Milk exosome-liposome hybrid vesicles (mExos@DSPE-Hyd-PMPC) achieved 2.4× semaglutide encapsulation efficiency over natural exosomes and 8.7% oral bioavailability through pH-responsive surface adaptation that overcomes sequential gut absorption barriers.","whyItMatters":"Oral peptide delivery is the holy grail of drug delivery — most peptide drugs require injection. Achieving 8.7% oral bioavailability for semaglutide using a milk-derived natural carrier is a major step toward needle-free peptide therapies.","specificNumbers":"Hybrid vesicles significantly improved oral bioavailability compared to exosomes or liposomes alone. Published in ACS Nano.","methodology":"Hybrid vesicles created by fusing functionalized liposomes (containing pH-sensitive hydrazone-linked zwitterionic polymer) with natural milk exosomes. Characterized for semaglutide loading, mucus penetration, epithelial barrier crossing, and oral bioavailability in animal models.","limitations":"Animal study — human gastrointestinal conditions differ from the models used. Manufacturing scalability of exosome-liposome hybrids is uncertain. Long-term stability and shelf life haven't been assessed. Regulatory pathway for milk exosome-based drug delivery is unclear."},{"rthcId":"RPEP-09561","title":"A novel angiotensin I-converting enzyme inhibitory peptide from walnut (Juglans sigillata) protein hydrolysates and its evaluation in Ang II-induced HUVECs and hypertensive rats.","authors":"Xie, Jinxiang; Chen, Shupeng; Huan, Pengtao; Wang, Shuguang; Zhuang, Yongliang","year":2024,"journal":"International journal of biological macromolecules, 266(Pt 2), 131152","doi":"10.1016/j.ijbiomac.2024.131152","pmid":"38556230","tags":["bioactive-peptides","cardiovascular-health"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"FDWLR from walnut protein (IC50 8.02 μg/mL ACE inhibition) demonstrated triple validation: in vitro ACE blocking, HUVEC vasoprotection against angiotensin II, and in vivo blood pressure lowering in spontaneously hypertensive rats.","whyItMatters":"Walnuts have long been associated with heart health, but this study identifies a specific peptide responsible and proves it works through multiple validated experiments — moving beyond epidemiological associations to molecular-level evidence.","specificNumbers":"Most potent peptide identified from walnut hydrolysate. Validated through in vitro ACE inhibition, HUVEC protection, and blood pressure reduction in SHR rats.","methodology":"Walnut protein hydrolyzed by alcalase + simulated GI digestion. Peptides separated by Sephadex-G25, identified by peptidomics, screened via PeptideRanker and in silico analysis. Validated by ACE inhibition assay, molecular docking, ADMET prediction, HUVEC angiotensin II challenge, and oral administration to SHR.","limitations":"Animal study using spontaneously hypertensive rats. The human dose needed for blood pressure effects is unknown. In silico ADMET predictions need confirmation with actual pharmacokinetic studies. Long-term safety data is lacking."},{"rthcId":"RPEP-09562","title":"Seven glucagon-like peptide-1 receptor agonists and polyagonists for weight loss in patients with obesity or overweight: an updated systematic review and network meta-analysis of randomized controlled trials.","authors":"Xie, Zeyu; Zheng, Guimei; Liang, Zhuoru; Li, Mengting; Deng, Weishang; Cao, Weiling","year":2024,"journal":"Metabolism: clinical and experimental, 161, 156038","doi":"10.1016/j.metabol.2024.156038","pmid":"39305981","tags":["semaglutide","tirzepatide","glp-1-agonists","weight-management"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Retatrutide 12mg (−22.1% body weight, −17cm waist) and tirzepatide 15mg (−16.5%) were the most effective weight loss treatments. Dual/triple receptor agonists significantly outperformed single GLP-1 receptor agonists across 27 RCTs with 15,584 patients.","whyItMatters":"With multiple GLP-1 weight loss drugs now available or in development, clinicians and patients need evidence-based comparisons. This analysis shows multi-receptor agonists represent the next frontier, with retatrutide potentially doubling the weight loss of earlier drugs like liraglutide.","specificNumbers":"Drugs compared: mazdutide (6/4.5mg), retatrutide (12/8mg), tirzepatide (15/10mg), liraglutide 3.0mg, semaglutide (2.4/1.0mg). RCTs with ≥16-week duration.","methodology":"Network meta-analysis of 27 RCTs (≥16 weeks duration) from Cochrane Library, PubMed, and Embase through August 2024. Compared mazdutide, retatrutide, tirzepatide, liraglutide, semaglutide, orforglipron, and beinaglutide. Frequentist random-effects model using Stata 16.1.","limitations":"Some drugs (retatrutide, mazdutide) have fewer trials and shorter follow-up than established drugs like semaglutide. Long-term safety data beyond trial periods is unavailable for newer agents. The network meta-analysis relies on indirect comparisons for some drug pairs. Weight regain after discontinuation wasn't assessed."},{"rthcId":"RPEP-09563","title":"Adverse Events of Oral GLP-1 Receptor Agonist (Semaglutide Tablets): A Real-World Study Based on FAERS from 2019 to 2023.","authors":"Xiong, Si; Gou, Ruoyu; Liang, Xudong; Wu, Hao; Qin, Shuitao; Li, Bing; Luo, Changjun; Chen, Junan","year":2024,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 15(8), 1717-1733","doi":"10.1007/s13300-024-01594-7","pmid":"38776037","tags":["semaglutide","glp-1-agonists"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"From 2,398 FAERS reports (5,653 adverse events), 23 system organ classes and 93 preferred terms showed significant signals for oral semaglutide, with metabolism/nutrition disorders most signaled and unexpected findings of acute cholecystitis, abducens nerve paralysis, and positional vertigo.","whyItMatters":"As oral semaglutide becomes widely prescribed for diabetes and weight management, understanding its real-world safety profile beyond clinical trials is critical. The identification of unexpected adverse events like nerve paralysis and acute cholecystitis informs prescribers and patients.","specificNumbers":"FAERS data covering 2019-2023 (4 years of post-marketing surveillance). GI events most frequently reported.","methodology":"Retrospective analysis of FDA FAERS database (Q3 2019 to Q3 2023) for oral semaglutide. Data mining using four signal quantification methods: ROR, PRR, BCPNN, and MGPS for cross-validation.","limitations":"FAERS is a voluntary reporting system subject to reporting bias — not all adverse events are reported, and reports don't prove causation. The oral formulation's adverse event profile may partly reflect the unique absorption enhancer (SNAC) rather than semaglutide itself. Reporting rates are influenced by media attention and awareness."},{"rthcId":"RPEP-09564","title":"Liraglutide combined with routine therapy improves renal function, renal fibrosis, immune status, and prognosis of type 2 diabetes patients.","authors":"Xiong, Wen; Liu, Hongxia; Xiang, Bo; Shang, Guangyu","year":2024,"journal":"American journal of translational research, 16(7), 3405-3412","doi":"10.62347/VYSW5854","pmid":"39114730","tags":["liraglutide","glp-1-agonists","kidney-health"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Liraglutide + standard therapy achieved 97.6% effectiveness vs 78.6% for standard therapy alone, with significantly better blood glucose control, kidney function (Scr, BUN, 24h-UPor), renal fibrosis reduction, and immunoglobulin levels in 84 T2DM patients.","whyItMatters":"Diabetic kidney disease is the leading cause of kidney failure worldwide. Evidence that liraglutide not only controls blood sugar but also directly improves kidney function and reduces fibrosis supports its use as a kidney-protective therapy for diabetic patients.","specificNumbers":"84 patients total (42 per group). Study period: March 2021 to March 2022. Improvements in renal function, fibrosis markers, and immune parameters.","methodology":"Retrospective analysis of 84 T2DM patients (42 per group) at First Affiliated Hospital of Jishou University (March 2021–March 2022). Control group received routine treatment; study group added liraglutide. Compared blood glucose, renal function, renal fibrosis markers, immunoglobulin levels, and adverse reactions.","limitations":"Retrospective, non-randomized design at a single hospital with a small sample size (42 per group). The higher adverse reaction rate in the liraglutide group (19.1%) is notable and warrants attention. Short follow-up period. The study didn't control for all potential confounders."},{"rthcId":"RPEP-09565","title":"Molybdenum disulfide nanosheets based non-oxygen-dependent and heat-initiated free radical nanogenerator with antimicrobial peptides for antimicrobial, biofilm ablation and wound healing.","authors":"Xu, Guanglin; Peng, Guanglan; Yang, Jianping; Wu, Mingcai; Li, Wanzhen; Wang, Jun; Zhu, Longbao; Zhang, Weiwei; Ge, Fei; Song, Ping","year":2024,"journal":"Biomaterials advances, 162, 213920","doi":"10.1016/j.bioadv.2024.213920","pmid":"38901063","tags":["antimicrobial-peptides","wound-healing","drug-delivery"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"AIPH/AMP/MoS2 composite nanosheets achieved MIC of 38 μg/mL against MDR E. coli and 30 μg/mL against MDR S. aureus, destroyed >85% of biofilms under NIR irradiation, and healed ~90% of wounds in 4 days through synergistic photothermal, free radical, and AMP mechanisms.","whyItMatters":"Drug-resistant bacterial infections in chronic wounds are a growing crisis with few effective treatments. This oxygen-independent approach works precisely in the hypoxic conditions found in chronic wounds, where conventional therapies often fail.","specificNumbers":"Three combined mechanisms: photothermal MoS2, oxygen-independent AIPH radical generation, and AMP delivery. Effective against MDR bacteria and biofilms.","methodology":"Synthesized AIPH/AMP/MoS2 composite nanosheets and characterized photothermal properties (808nm NIR), free radical generation, and antimicrobial peptide delivery. Tested MICs against MDR bacteria, biofilm ablation under NIR, biocompatibility (hemolysis and MEF cytotoxicity), and wound healing in mouse models. Transcriptome analysis revealed mechanisms.","limitations":"Mouse wound model — human chronic wounds involve more complex tissue environments and patient factors. The need for NIR laser irradiation limits practical application. Long-term safety of MoS2 nanosheets in wounds is unknown. Manufacturing scalability hasn't been addressed."},{"rthcId":"RPEP-09566","title":"Meta learning for mutant HLA class I epitope immunogenicity prediction to accelerate cancer clinical immunotherapy.","authors":"Xu, Long; Yang, Qiang; Dong, Weihe; Li, Xiaokun; Wang, Kuanquan; Dong, Suyu; Zhang, Xianyu; Yang, Tiansong; Luo, Gongning; Liao, Xingyu; Gao, Xin; Wang, Guohua","year":2024,"journal":"Briefings in bioinformatics, 26(1)","doi":"10.1093/bib/bbae625","pmid":"39656887","tags":["bioactive-peptides","cancer-research","immune-function"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"MHLAPre achieved significant improvement over five state-of-the-art models in identifying immunogenic neoepitopes for cancer immunotherapy, using meta-learning on MS-derived HLA ligandome data with transfer learning from pHLA-TCR interaction datasets.","whyItMatters":"Selecting the right neoantigens is the single biggest challenge in personalized cancer vaccines. Better prediction tools mean vaccines that are more likely to trigger the immune system — potentially transforming cancer immunotherapy from trial-and-error to precision medicine.","specificNumbers":"Meta-learning outperformed existing tools on immunogenicity prediction despite using limited training data.","methodology":"Meta-learning model trained on large-scale MS-derived HLA class I eluted ligandome data. Provides allele-specific and pan-allelic prediction. Transfer learning applied using pHLA-TCR interaction data. Benchmarked against 5 existing prediction tools on neoepitope immunogenicity identification.","limitations":"Prediction accuracy is limited by the quality and completeness of training data. Some HLA alleles have much more data than others. In silico predictions still need experimental validation. The model's performance may vary across different cancer types and HLA populations."},{"rthcId":"RPEP-09567","title":"Ghrelin Induces the Production of Hypothalamic NPY Through the AMPK-mTOR Pathway to Alleviate Cancer-induced Bone Pain.","authors":"Xu, Longjie; Hou, Lili; Cao, Chun; Li, Xiaohua","year":2024,"journal":"In vivo (Athens, Greece), 38(3), 1133-1142","doi":"10.21873/invivo.13548","pmid":"38688635","tags":["ghrelin","neuropeptides","pain-management"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Ghrelin activated the hypothalamic AMPK-mTOR pathway to induce NPY production, alleviating cancer-induced bone pain in rats. NPY's antinociceptive effect was mediated through Y1 and Y2 receptors and reversed by GHS-R1α antagonism.","whyItMatters":"Cancer bone pain is often inadequately controlled with existing analgesics. Discovering that ghrelin and NPY — naturally occurring peptides — can modulate this specific type of pain through a defined brain pathway opens entirely new therapeutic approaches.","specificNumbers":"CIBP mouse model with exogenous NPY administration and NPY receptor antagonist testing. AMPK-mTOR pathway confirmed as mediator.","methodology":"Cancer-induced bone pain model established in rats. Intracerebroventricular administration of NPY, NPY receptor antagonists (Y1R, Y2R), and ghrelin. Measured body weight, food intake, behavioral pain indicators, and hypothalamic ghrelin, NPY, and AMPK-mTOR pathway markers.","limitations":"Animal study using an intracerebroventricular injection route, which isn't practical for clinical use. The short-term nature of NPY's pain relief may limit standalone therapeutic utility. Translation from rat brain to human brain pain processing is uncertain."},{"rthcId":"RPEP-09568","title":"Exenatide administration time-dependently affects the hepatic circadian clock through glucagon-like peptide-1 receptors in the central nervous system.","authors":"Xu, Pingping; Morishige, Jun-Ichi; Jing, Zheng; Nagata, Naoto; Shi, Yifan; Iba, Tomohiro; Daikoku, Takiko; Ono, Masanori; Maida, Yoshiko; Fujiwara, Tomoko; Fujiwara, Hiroshi; Ando, Hitoshi","year":2024,"journal":"Biochemical pharmacology, 230(Pt 1), 116567","doi":"10.1016/j.bcp.2024.116567","pmid":"39369911","tags":["exenatide","glp-1-agonists","circadian-rhythm"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Exenatide time-dependently modulates the hepatic circadian clock through CNS GLP-1 receptors. Morning-equivalent dosing (ZT12) counteracted clock disruption from irregular eating; evening-equivalent dosing (ZT0) worsened it. CNS GLP-1 receptor knockdown attenuated these effects.","whyItMatters":"Circadian disruption is increasingly linked to metabolic disease. This provides a scientific rationale for morning dosing of GLP-1 agonists — and suggests an additional mechanism (clock restoration) beyond the known effects on appetite and blood sugar.","specificNumbers":"Time-dependent effects on hepatic clock genes observed. CNS-specific GLP1R knockdown eliminated the liver clock effects.","methodology":"Male C57BL/6J and CNS-specific GLP-1 receptor knockdown (GLP1RKD) mice under 12h/12h light/dark cycle. Time-restricted feeding to either light (L-TRF) or dark (D-TRF) period. Exenatide administered 4-5 times daily at ZT12 or ZT0. Hepatic clock gene expression rhythms analyzed by mRNA expression.","limitations":"Mouse study with controlled feeding schedules that don't mirror human eating patterns. Only clock gene mRNA was measured, not long-term metabolic outcomes. The translation to once-weekly GLP-1 agonists (semaglutide, tirzepatide) versus daily exenatide isn't clear."},{"rthcId":"RPEP-09569","title":"Peptide Receptor Radionuclide Therapy and clinical associations with renal and hematological toxicities and survival in patients with neuroendocrine tumors: an analysis from two U.S. medical centers.","authors":"Xu, Tao; Dillon, Joseph S; Maluccio, Mary A; Quelle, Dawn E; Nash, Sarah H; Cho, Hyunkeun; Limbach, Kristen E; Skill, Nicholas J; Bren-Mattison, Yvette; O'Rorke, Michael A","year":2024,"journal":"Journal of cancer research and clinical oncology, 150(11), 485","doi":"10.1007/s00432-024-06020-w","pmid":"39488644","tags":["somatostatin-analogs","cancer-research"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Among 448 NET patients, ¹⁷⁷Lu-DOTATATE (n=335) showed no significant renal toxicity difference from ⁹⁰Y-DOTATOC (n=113) but caused more hematological effects. ¹⁷⁷Lu-DOTATATE was associated with significantly longer PFS (HR 0.47, P=0.004) but no OS difference.","whyItMatters":"PRRT is a mainstay of neuroendocrine tumor treatment, and choosing between ¹⁷⁷Lu and ⁹⁰Y agents involves balancing efficacy against toxicity. This large real-world comparison provides evidence that ¹⁷⁷Lu-DOTATATE offers superior tumor control with manageable side effects.","specificNumbers":"448 patients across two US centers. Both 177Lu-DOTATATE and 90Y-DOTATOC forms of PRRT analyzed. Kidney and blood toxicity tracked over treatment course.","methodology":"Retrospective cohort of 448 NET patients (335 ¹⁷⁷Lu-DOTATATE, 113 ⁹⁰Y-DOTATOC). Renal function tracked via creatinine, BUN, eGFR. Hematological function via WBC, platelets, hemoglobin. Piecewise linear mixed-effect models for longitudinal data. Cox proportional hazard regression for OS and PFS.","limitations":"Retrospective design with potential selection bias. The two treatment groups may differ in baseline characteristics. Long-term renal effects beyond the follow-up period weren't captured. The study doesn't account for prior or concurrent therapies."},{"rthcId":"RPEP-09570","title":"Update on Perioperative Medication Management for the Hand Surgeon: A Focus on Diabetes, Weight Loss, Rheumatologic, and Antithrombotic Medications.","authors":"Xu, Wen; Schmiesing, Cliff; Chang, James","year":2024,"journal":"The Journal of hand surgery, 49(10), 1012-1020","doi":"10.1016/j.jhsa.2024.05.018","pmid":"39093237","tags":["semaglutide","tirzepatide","glp-1-agonists"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"GLP-1 receptor agonists cause delayed gastric emptying that increases aspiration risk under anesthesia. Discontinuation before surgery is imperative, and SGLT-2 inhibitors pose a separate risk of severe diabetic ketoacidosis perioperatively.","whyItMatters":"Millions of patients are now taking GLP-1 agonists, and many will undergo surgery. Failure to stop these drugs before anesthesia can cause life-threatening aspiration. Every surgeon — not just endocrinologists — needs to know this.","specificNumbers":"Review covers semaglutide (Ozempic, Wegovy), tirzepatide (Mounjaro), dapagliflozin (Farxiga), and empagliflozin (Jardiance) among others.","methodology":"Narrative review of current literature and clinical guidelines on perioperative management of diabetes/weight loss medications (GLP-1 RAs, SGLT-2i), antithrombotic medications, and RA immunosuppressants for surgical procedures.","limitations":"Narrative review without systematic methodology. Perioperative guidelines are still evolving as more real-world data accumulates. The optimal timing of drug discontinuation before surgery varies by drug and hasn't been definitively established for all agents."},{"rthcId":"RPEP-09571","title":"Antimicrobial Peptide CATH-2 Attenuates Avian Pathogenic E. coli-Induced Inflammatory Response via NF-κB/NLRP3/MAPK Pathway and Lysosomal Dysfunction in Macrophages.","authors":"Xu, Yating; Xu, Liuyi; Zhang, Tingting; Tian, Hongliang; Lu, Yi; Jiang, Sha; Cao, Xuefeng; Li, Zhiwei; Hu, Xiaoxiang; Fang, Rendong; Peng, Lianci","year":2024,"journal":"International journal of molecular sciences, 25(23)","doi":"10.3390/ijms252312572","pmid":"39684284","tags":["antimicrobial-peptides","immune-function","inflammation"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"CATH-2 reduced IL-1β, IL-6, IL-1α, and IL-12 production during APEC infection by inhibiting NLRP3 inflammasome activation, NF-κB and MAPK signaling, and disrupting lysosomal function. Restoring lysosomal acidification reversed CATH-2's anti-inflammatory effects.","whyItMatters":"Understanding how antimicrobial peptides control inflammation — not just kill bacteria — opens new therapeutic strategies. CATH-2's ability to simultaneously block three inflammatory pathways through lysosomal disruption reveals a sophisticated immune regulation mechanism shared across species.","specificNumbers":"CATH-2 reduced IL-1β, IL-6, IL-1α, and IL-12 production. Suppressed NF-κB, NLRP3, and MAPK pathway activation.","methodology":"Murine peritoneal macrophages primed with CATH-2 and infected with avian pathogenic E. coli. Measured cytokine production, caspase-1 activation, ASC speck formation, NF-κB/MAPK pathway activation, cathepsin B expression, and lysosomal acidification. ML-SA1 rescue experiment confirmed lysosomal mechanism.","limitations":"In vitro study using murine macrophages and avian E. coli — the clinical relevance to human infections is unclear. The lysosomal disruption mechanism could have off-target effects in whole organisms. Only one type of immune cell was studied."},{"rthcId":"RPEP-09572","title":"Meta-analysis of the clinical efficacy of liraglutide in treating type 2 diabetes mellitus complicated with non-alcoholic fatty liver disease.","authors":"Xu, Yuan-Yuan; Wang, Xu; She, Yu-Qing; Liu, Jie; Zhang, Qing","year":2024,"journal":"Endocrine journal, 71(9), 881-894","doi":"10.1507/endocrj.EJ24-0168","pmid":"38910131","tags":["liraglutide","glp-1-agonists","liver-health","metabolic-health"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Liraglutide significantly reduced BMI (MD −1.06), triglycerides (MD −0.35 mmol/L), visceral adipose tissue (MD −21.06 cm²), and subcutaneous adipose tissue (MD −20.53 cm²) in T2DM patients with NAFLD across 12 studies.","whyItMatters":"T2DM and NAFLD together create a vicious cycle of insulin resistance, inflammation, and fat accumulation. Liraglutide breaks this cycle by reducing visceral fat (the metabolically dangerous fat around organs) while improving glucose and lipid parameters — addressing root causes rather than just symptoms.","specificNumbers":"12 studies included. 13 outcome measures analyzed. Literature through December 2023.","methodology":"Systematic review and meta-analysis of 12 studies from PubMed, Web of Science, and NLM databases through December 2023. Compared liraglutide to placebo or other drugs (mainly insulin). Analyzed using Stata 15.1 software.","limitations":"The meta-analysis included only 12 studies, with heterogeneous comparator groups (placebo vs insulin vs other drugs). The impact on liver histology (the gold standard for NAFLD assessment) wasn't analyzed. Long-term liver-specific outcomes (fibrosis progression, cirrhosis) weren't captured."},{"rthcId":"RPEP-09573","title":"Liraglutide alleviates high-fat diet-induced kidney injury in mice by regulating the CaMKKβ/AMPK pathway.","authors":"Xuan, Yingli; Ding, Ting-Ting; Mao, Xiao-Lei; Pang, Shiqing; He, Ruibin; Qin, Li; Yuan, Jiang Zi","year":2024,"journal":"Renal failure, 46(1), 2351473","doi":"10.1080/0886022X.2024.2351473","pmid":"38915241","tags":["liraglutide","glp-1-agonists","kidney-health"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Liraglutide (0.6 mg/kg for 12 weeks) protected against HFD-induced kidney injury by reducing serum lipids, improving kidney function markers, reversing kidney pathology, and inhibiting the CaMKKβ/AMPK signaling pathway. Bortezomib (AMPK agonist) partially reversed these effects.","whyItMatters":"Obesity-related kidney disease is a growing epidemic with no targeted treatment. Demonstrating that liraglutide directly protects kidneys through a defined molecular pathway (not just through weight loss) could expand its clinical indications to include kidney protection in obese patients.","specificNumbers":"36 mice in 6 groups (n=6). High-fat diet-induced nephropathy model. CaMKKβ/AMPK pathway activation confirmed as mechanism.","methodology":"36 C57BL/6J male mice in 6 groups (n=6). Obesity-related kidney disease induced by 12 weeks HFD, then 12 weeks of liraglutide (0.6 mg/kg) or bortezomib (200 μg/kg). Measured serum lipids, kidney function (Scr, BUN, urinary protein), kidney histology (H&E, PAS staining), and CaMKKβ/AMPK pathway activation (IHC, western blot, RT-qPCR).","limitations":"Small animal study (6 mice per group). Only 12 weeks of treatment may not capture long-term kidney outcomes. The use of bortezomib (primarily a proteasome inhibitor) as an AMPK agonist adds complexity to interpretation. Human kidney disease involves factors beyond what HFD models capture."},{"rthcId":"RPEP-09574","title":"PIONEER REAL Japan: Primary results from a multicenter, prospective, real-world study of oral semaglutide in adults with type 2 diabetes in Japanese clinical practice.","authors":"Yabe, Daisuke; Hamamoto, Yoshiyuki; Kawanami, Daiji; Nishimura, Rimei; Terauchi, Yasuo; Amadid, Hanan; Braae, Uffe Christian; Major-Pedersen, Atheline; Suzuki, Ryo","year":2024,"journal":"Journal of diabetes investigation, 15(11), 1566-1577","doi":"10.1111/jdi.14291","pmid":"39172634","tags":["semaglutide","glp-1-agonists","metabolic-health"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Oral semaglutide reduced HbA1c by −0.7% and body weight by −2.8 kg in 624 Japanese T2DM adults over 34-44 weeks. Benefits were maintained in patients ≥75 years (HbA1c −0.5%, weight −2.7 kg). 25.8% reported adverse events, mostly gastrointestinal.","whyItMatters":"Real-world evidence in an Asian population is critical because drug metabolism and diabetes phenotypes differ from Western populations studied in clinical trials. Confirming efficacy and safety in elderly Japanese patients addresses a significant evidence gap.","specificNumbers":"Follow-up: 34-44 weeks. Population: injection-naïve T2DM adults in Japanese clinical practice.","methodology":"Non-interventional, multicenter, prospective, real-world study. 624 adults naïve to injectable glucose-lowering therapies initiated oral semaglutide in routine practice and were followed for 34-44 weeks. Subgroup analyses for age <75 and ≥75 years.","limitations":"Non-interventional study without a control group. Only 34-44 weeks of follow-up. Japanese population may not be fully generalizable to other Asian or non-Asian groups. Selection bias — only patients prescribed oral semaglutide in practice were included."},{"rthcId":"RPEP-09575","title":"The Impact of Posttreatment Imaging in Peptide Receptor Radionuclide Therapy.","authors":"Yadav, Surekha; Lawhn-Heath, Courtney; Paciorek, Alan; Lindsay, Sheila; Mirro, Rebecca; Bergsland, Emily K; Hope, Thomas A","year":2024,"journal":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 65(3), 409-415","doi":"10.2967/jnumed.123.266614","pmid":"38428966","tags":["somatostatin-analogs","cancer-research"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Post-treatment SPECT/CT imaging at 24 hours after PRRT provided qualitative response assessments that impacted clinical management decisions in 100 NET patients undergoing peptide receptor radionuclide therapy.","whyItMatters":"PRRT is an expensive, specialized treatment with potential toxicity. Understanding whether post-treatment imaging provides actionable information helps optimize treatment protocols, potentially avoiding unnecessary additional cycles or identifying non-responders earlier.","specificNumbers":"100 patients evaluated. Post-treatment SPECT/CT performed at 24 hours after PRRT.","methodology":"Retrospective study of 100 patients with advanced well-differentiated neuroendocrine tumors undergoing PRRT with post-treatment SPECT/CT at 24 hours. Qualitative response assessed at each cycle and cross-referenced with chart review of management changes.","limitations":"Retrospective design. Single-center study. Qualitative (not quantitative) imaging assessment, which is more subjective. The specific clinical outcomes associated with imaging-guided management changes weren't reported in detail."},{"rthcId":"RPEP-09576","title":"Real-world safety profile of once-weekly semaglutide in people with type 2 diabetes: Analysis of pooled data from the SemaglUtide Real-world Evidence (SURE) programme.","authors":"Yale, Jean-François; Major-Pedersen, Atheline; Catarig, Andrei-Mircea; Jain, Rashmi; Menzen, Markus; Holmes, Patrick","year":2024,"journal":"Diabetes, obesity & metabolism, 26(10), 4429-4440","doi":"10.1111/dom.15794","pmid":"39118222","tags":["semaglutide","glp-1-agonists"],"studyType":"cohort","evidenceStrength":"strong","keyFinding":"Among 3,505 T2D patients in real-world practice, once-weekly semaglutide showed 24.3% AE rate (mostly mild GI), 5.1% discontinuation rate, 0.5% serious ADRs, and 0.1% severe hypoglycemia — consistent with phase 3 RCT safety data.","whyItMatters":"Real-world safety data is essential because clinical trial participants are carefully selected and monitored. Confirming semaglutide's safety across 3,505 unselected patients in routine practice gives prescribers and patients confidence that the drug is safe outside controlled settings.","specificNumbers":"9 SURE studies pooled. ~30-week duration each. Multiple subpopulations analyzed including elderly, obese, and renal impairment.","methodology":"Post hoc pooled analysis of nine SURE programme real-world studies (~30 weeks each). Collected safety data including AEs, serious AEs, hypoglycemic events, and treatment discontinuations. Analyzed for total population and subgroups based on baseline characteristics, co-medications, and prescriber specialty.","limitations":"Observational studies lack the rigor of randomized trials. About 30 weeks of follow-up may miss longer-term safety signals. Subgroup analyses are hypothesis-generating, not definitive. Voluntary adverse event reporting may lead to underreporting."},{"rthcId":"RPEP-09577","title":"Is the efficacy of oxytocin for autism diminished at higher dosages or repeated doses?: Potential mechanisms and candidate solutions.","authors":"Yamasue, Hidenori","year":2024,"journal":"Peptides, 171, 171133","doi":"10.1016/j.peptides.2023.171133","pmid":"38072084","tags":["oxytocin","neurological-conditions"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Single-dose oxytocin trials consistently show efficacy for autism core symptoms, but repeated administration yields mixed results. Diminishing efficacy at higher/repeated doses may involve oxytocin-vasopressin receptor cross-talk and receptor desensitization.","whyItMatters":"Autism has no approved pharmacological treatment for core symptoms. Understanding why oxytocin's initial promise fades with repeated use is crucial for developing effective long-term peptide-based therapies for this prevalent condition.","specificNumbers":"Multiple single-dose trials show efficacy. Repeated dosing and higher dose trials show diminished or absent effects.","methodology":"Narrative review of published studies on oxytocin for autism, examining single-dose versus repeated-dose trial outcomes, potential mechanisms of diminished efficacy, and candidate strategies for optimization.","limitations":"Narrative review without systematic methodology. The mechanisms proposed (receptor cross-talk, desensitization) are theoretical and not fully proven. Oxytocin research in autism is complicated by heterogeneous study designs, dosing protocols, and outcome measures."},{"rthcId":"RPEP-09578","title":"Cardiometabolic Modulation by Semaglutide Contributes to Cardioprotection in Rats with Myocardial Infarction.","authors":"Yan, Haihao; Yao, Wenjing; Li, Yanhong; Li, Tianxing; Song, Kexin; Yan, Pan; Dang, Yi","year":2024,"journal":"Drug design, development and therapy, 18, 5485-5500","doi":"10.2147/DDDT.S491970","pmid":"39640291","tags":["semaglutide","glp-1-agonists","cardiovascular-health"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Semaglutide improved cardiac function, reduced histopathological damage, and altered the cardiac metabolomic profile after myocardial infarction in rats, suggesting cardioprotection through metabolic modulation rather than just glycemic control.","whyItMatters":"The SELECT trial showed semaglutide reduces cardiovascular events in humans, but the mechanism wasn't clear. This study provides mechanistic evidence that semaglutide directly protects the heart through metabolic reprogramming, independent of weight loss.","specificNumbers":"24 rats in 3 groups (n=8 per group). Echocardiographic improvement and reduced histopathological damage in semaglutide group.","methodology":"24 male Sprague-Dawley rats in 3 groups (control, MI, semaglutide-treated). Measured weight, blood glucose, lipid profiles. Cardiac function assessed by echocardiography. Heart tissue evaluated by histopathology and immunohistochemistry. Untargeted metabolomic analysis using LC-MS/MS.","limitations":"Small animal study (8 per group) with a non-human MI model. The specific cardioprotective metabolites identified need validation. Translation from rat cardiac metabolism to human post-MI care is uncertain. Duration of semaglutide treatment wasn't specified in the abstract."},{"rthcId":"RPEP-09579","title":"Intranasal Delivery of Cell-Penetrating Therapeutic Peptide Enhances Brain Delivery, Reduces Inflammation, and Improves Neurologic Function in Moderate Traumatic Brain Injury.","authors":"Yanamadala, Yaswanthi; Roy, Ritika; Williams, Afrika Alake; Uppu, Navya; Kim, Audrey Yoonsun; DeCoster, Mark A; Kim, Paul; Murray, Teresa Ann","year":2024,"journal":"Pharmaceutics, 16(6)","doi":"10.3390/pharmaceutics16060774","pmid":"38931895","tags":["bioactive-peptides","drug-delivery","neurological-conditions"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Intranasal KAFAK peptide traversed the BBB in TBI mice, reduced proinflammatory cytokines contributing to secondary injury, and improved or restored neurological, memory, and locomotor function after moderate traumatic brain injury.","whyItMatters":"TBI affects millions annually and is a leading cause of disability, yet there's no approved treatment for the secondary brain damage caused by chronic inflammation. An intranasal peptide that reduces brain inflammation and restores function could be a game-changer.","specificNumbers":"Moderate TBI model with intranasal peptide delivery showing enhanced brain uptake and reduced inflammatory markers.","methodology":"Murine model of diffuse, moderate TBI. KAFAK administered intranasally (non-invasive). BBB penetration confirmed. Proinflammatory cytokine levels measured. Behavioral tests assessed neurological function, memory, and locomotor performance.","limitations":"Mouse study — TBI models don't fully replicate human brain injury complexity. The exact dose, timing, and duration of KAFAK treatment needed for optimal benefit weren't fully defined. Long-term safety and the sustainability of functional improvements weren't assessed."},{"rthcId":"RPEP-09580","title":"Investigation of the Interaction Between Angiotensin-Converting Enzyme (ACE) and ACE-Inhibitory Tripeptide from Casein.","authors":"Yang, Cuicui; Xie, Tianzhao; Cai, Mengmeng; Xu, Xiaoting; Li, Muzijun; Liu, Pengru; Lan, Xiongdiao","year":2024,"journal":"International journal of molecular sciences, 25(23)","doi":"10.3390/ijms252313021","pmid":"39684732","tags":["bioactive-peptides","cardiovascular-health"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"The casein-derived tripeptide LLY demonstrated high ACE-inhibitory activity with excellent stability. Systematic investigation revealed the molecular details of LLY-ACE binding interactions important for understanding and designing antihypertensive peptides.","whyItMatters":"Milk-derived ACE-inhibitory peptides are among the most studied food-derived bioactives. Detailed molecular mapping of how LLY binds ACE advances both the science of food-derived antihypertensives and the rational design of more potent peptide candidates.","specificNumbers":"LLY (Leu-Leu-Tyr) showed high ACE inhibitory activity with specific binding interactions characterized at the molecular level.","methodology":"ACE-inhibitory peptide LLY isolated from casein hydrolysate. ACE-inhibitory activity and stability tested. LLY-ACE interaction characterized through systematic molecular investigation techniques.","limitations":"In vitro study — ACE inhibition in a test tube doesn't guarantee blood pressure lowering in humans. The specific IC50 value wasn't reported in the available abstract. Bioavailability after actual dairy consumption is unknown."},{"rthcId":"RPEP-09581","title":"Anti-Photoaging Effects of Antioxidant Peptide from Seahorse (Hippocampus abdominalis) in In Vivo and In Vitro Models.","authors":"Yang, Fengqi; Yang, Yang; Xiao, Dandan; Kim, Poongho; Lee, Jihee; Jeon, You-Jin; Wang, Lei","year":2024,"journal":"Marine drugs, 22(10)","doi":"10.3390/md22100471","pmid":"39452879","tags":["bioactive-peptides","skin-health"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"SHP2 from seahorse hydrolysate protected keratinocytes from UVB by reducing ROS and apoptosis, inhibited MMPs in fibroblasts while promoting collagen synthesis, and demonstrated anti-photoaging effects in a zebrafish model.","whyItMatters":"The anti-aging skincare market is massive, and consumers increasingly seek bioactive peptide ingredients with scientific backing. SHP2 addresses the two main mechanisms of skin aging — oxidative damage and collagen loss — making it a strong candidate for evidence-based cosmeceuticals.","specificNumbers":"SHP2 improved cell viability, reduced ROS, attenuated apoptosis markers, and decreased inflammatory cytokines in UVB-exposed skin cells.","methodology":"SHP2 peptide purified from seahorse (Hippocampus abdominalis) alcalase hydrolysate. Tested on UVB-irradiated HaCaT keratinocytes (cell viability, ROS, apoptosis) and HDF fibroblasts (MMP inhibition, collagen synthesis). In vivo validation in a zebrafish photoaging model.","limitations":"Cell culture and zebrafish models — human skin is more complex. The specific MMP subtypes inhibited weren't detailed. Formulation stability, skin penetration, and clinical efficacy in human subjects haven't been tested. Seahorse sustainability and sourcing is an ethical concern."},{"rthcId":"RPEP-09582","title":"Nppb contributes to Sepsis-Induced myocardial injury by regulating Senescence-Related genes.","authors":"Yang, Hang; Jiang, Zhenjie; Feng, Lin; Wang, Chengyan; Xu, Haojie; Wu, Xiaodan; Lin, Caizhu; Zeng, Kai","year":2024,"journal":"International immunopharmacology, 143(Pt 2), 113461","doi":"10.1016/j.intimp.2024.113461","pmid":"39447413","tags":["neuropeptides","cardiovascular-health"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Heart-specific Nppb knockout improved sepsis-induced myocardial injury in mice. Seven differentially expressed genes overlapped with senescence genes, with CCL2 identified as the key mediator. Reducing Nppb lowered CCL2 expression and improved cardiac structure and function.","whyItMatters":"BNP has been used for decades as a diagnostic biomarker for heart failure, but this study reveals it's actually a driver of cardiac damage in sepsis — not just an innocent bystander. Targeting BNP or its downstream CCL2 pathway could become a new treatment strategy for septic cardiomyopathy.","specificNumbers":"Septic mice showed elevated Nppb, inflammatory markers, and senescence markers in cardiac tissue.","methodology":"Septic mouse models with serum inflammatory and myocardial injury markers assessed. Conditional heart-specific Nppb knockout mice developed. mRNA sequencing identified DEGs cross-referenced with senescence genes. Single-cell analysis confirmed CCL2 and macrophage involvement. Validated in Nppb knockout sepsis model.","limitations":"Mouse sepsis model may not fully replicate human septic cardiomyopathy. Complete Nppb knockout is an extreme intervention — partial or pharmacological BNP reduction would be more clinically relevant. The causal chain from Nppb to CCL2 to cardiac damage needs further mechanistic validation."},{"rthcId":"RPEP-09583","title":"Study on the design, synthesis, and activity of anti-tumor staple peptides targeting MDM2/MDMX.","authors":"Yang, Jian; Liao, Xiufei; Hu, Damin; Mo, Jinqiu; Gao, Xiurong; Liao, Hongli","year":2024,"journal":"Frontiers in chemistry, 12, 1403473","doi":"10.3389/fchem.2024.1403473","pmid":"38911993","tags":["bioactive-peptides","cancer-research","peptide-chemistry"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Stapled peptide SM3-4 dual-targeted MDM2/MDMX, induced tumor cell apoptosis at low μM concentrations in vitro, showed significantly increased helicity compared to linear peptides, and demonstrated that enhanced staple activity correlates with helicity.","whyItMatters":"MDM2/MDMX are among the most important cancer drug targets — blocking them reactivates p53 in the majority of tumors that retain wild-type p53. Stapled peptides solve the key challenges of peptide drugs (stability and cell entry), making them viable cancer therapeutics.","specificNumbers":"SM3-4 induced apoptosis at low μM concentrations. Significantly enhanced helix compared to linear counterparts.","methodology":"Designed and synthesized a series of PMI-M3-based stapled peptides with dual MDM2/MDMX targeting. Compared helicity, proteolysis resistance, cell penetration, and anti-tumor activity against straight-chain peptide controls. Tumor cell apoptosis tested in vitro.","limitations":"In vitro study only — tumor cell killing in culture doesn't guarantee efficacy in animals or humans. The specific tumor cell lines tested weren't detailed. Pharmacokinetics, biodistribution, and in vivo anti-tumor efficacy haven't been assessed."},{"rthcId":"RPEP-09584","title":"Meticulously engineered three-dimensional-printed scaffold with microarchitecture and controlled peptide release for enhanced bone regeneration.","authors":"Yang, Jin; Fatima, Kanwal; Zhou, Xiaojun; He, Chuanglong","year":2024,"journal":"Biomaterials translational, 5(1), 69-83","doi":"10.12336/biomatertransl.2024.01.007","pmid":"39220663","tags":["bioactive-peptides","bone-health","drug-delivery"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"PM@GS/PCL scaffold achieved 17.81 ± 0.83 MPa compressive strength, promoted MSC osteogenic differentiation (alizarin red and ALP staining), enhanced HUVEC migration and tube formation, and improved bone repair and vascularization in a rat femoral defect model.","whyItMatters":"Large load-bearing bone defects (from trauma, tumor removal, or degeneration) remain one of orthopedics' biggest challenges. A scaffold that combines mechanical strength, controlled peptide release, and dual promotion of bone and blood vessel growth addresses all the key requirements for successful repair.","specificNumbers":"3D-printed scaffold integrated mechanical support, controlled peptide release, and vascularization promotion.","methodology":"3D-printed PCL scaffold with GelMA/SFMA hydrogel interior containing PTH peptide-loaded mesoporous silica nanoparticles. Characterized physically and chemically. In vitro: compression testing, HUVEC angiogenesis assays (Transwell, tube formation), MSC osteogenic differentiation (alizarin red, ALP). In vivo: rat femoral defect model evaluated by micro-CT and histology.","limitations":"Rat femoral defect model doesn't fully replicate the mechanical demands and healing challenges of large human bone defects. Long-term PTH release kinetics and scaffold degradation behavior need longer-term assessment. Manufacturing complexity may limit clinical translation."},{"rthcId":"RPEP-09585","title":"Tirzepatide's innovative applications in the management of type 2 diabetes and its future prospects in cardiovascular health.","authors":"Yang, Jingqi; Gu, Yuncheng; Chen, Huaigang; Wang, Hong; Hong, Lang; Li, Bin; Yang, Liu","year":2024,"journal":"Frontiers in pharmacology, 15, 1453825","doi":"10.3389/fphar.2024.1453825","pmid":"39263564","tags":["tirzepatide","glp-1-agonists","weight-management","metabolic-health"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Tirzepatide across SURMOUNT/SURPASS trials achieved HbA1c reductions up to 2.24% and weight loss up to 11.2 kg with good tolerability. Cardiovascular benefits are promising based on surrogate markers but await dedicated outcome trials.","whyItMatters":"Tirzepatide represents a new class of dual-receptor agonists that outperforms single GLP-1 agonists. Understanding its full clinical profile — including cardiovascular effects — is essential as it becomes a first-line treatment option for T2DM and obesity.","specificNumbers":"Maximum HbA1c reduction: 2.24%. Maximum weight loss: 11.2 kg. Good tolerability across trials.","methodology":"Narrative review summarizing results from the SURMOUNT and SURPASS clinical trial programmes, evaluating efficacy, safety, and cardiovascular implications of tirzepatide.","limitations":"Review article dependent on published trial data. Cardiovascular outcomes from dedicated CVOTs are not yet available. Long-term safety beyond trial durations is unknown. Cost and access remain barriers."},{"rthcId":"RPEP-09586","title":"Semaglutide Reduces Cardiomyocyte Damage Caused by High-Fat Through HSDL2.","authors":"Yang, Lin; Pan, Xiaoyu; Pan, Zhenyu; Gao, Haina; Ban, Jiangli; Chen, Shuchun","year":2024,"journal":"Drug design, development and therapy, 18, 5501-5515","doi":"10.2147/DDDT.S495659","pmid":"39634723","tags":["semaglutide","glp-1-agonists","cardiovascular-health"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Semaglutide restored HSDL2 expression and reduced oxidative stress markers in cardiomyocytes of obese mice, identifying a novel HSDL2-mediated pathway for GLP-1 agonist cardioprotection against obesity-induced heart damage.","whyItMatters":"Understanding how GLP-1 agonists protect the heart beyond glucose control helps explain their cardiovascular benefits and could identify new drug targets (like HSDL2) for cardiac protection in obesity.","specificNumbers":"Oxidative stress markers elevated in high-fat conditions and reduced by semaglutide. HSDL2 expression modulated by both high fat and semaglutide.","methodology":"High-fat diet mouse model. Measured oxidative stress markers and HSDL2 expression in myocardium and serum. Evaluated semaglutide's impact on cardiomyocyte damage and HSDL2 regulation.","limitations":"Mouse study — cardiac lipid metabolism differs between species. The causal role of HSDL2 would need knockout/knockdown experiments for confirmation. Specific semaglutide doses and treatment duration weren't detailed."},{"rthcId":"RPEP-09587","title":"Effectiveness and safety of semaglutide in overweight/obese adults with or without type 2 diabetes: A systematic review and meta-analysis.","authors":"Yang, Liu; Duan, Xueyu; Hua, Peng; Wu, Shilin; Liu, Xiaobo","year":2024,"journal":"Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences, 29, 60","doi":"10.4103/jrms.jrms_693_23","pmid":"39629036","tags":["semaglutide","glp-1-agonists","weight-management"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Meta-analysis of RCTs confirmed semaglutide significantly reduces body weight in overweight/obese adults with or without T2DM compared to placebo, with consistent effects across multiple anthropometric and metabolic outcomes.","whyItMatters":"Establishes the comprehensive evidence base for semaglutide in weight management regardless of diabetes status, supporting its regulatory approval and clinical use for obesity as a standalone condition.","specificNumbers":"PROSPERO-registered systematic review. Multiple RCTs included from comprehensive database search.","methodology":"PROSPERO-registered systematic review and meta-analysis. Searched Embase, PubMed, and Cochrane Library for RCTs of semaglutide in overweight/obese adults. Evaluated body weight change, BMI, waist circumference, and safety outcomes.","limitations":"Specific numerical results weren't available in the abstract portion reviewed. Individual trial heterogeneity in doses, durations, and populations may affect pooled estimates. Publication bias is possible."},{"rthcId":"RPEP-09588","title":"Stratified analysis of the association between anti-obesity medications and digestive adverse events: a real-world study based on the FDA adverse event reporting system database.","authors":"Yang, Qing; Wang, Junyan; Wang, Menghuan; Zhang, Shuyu; He, Qin-Qin","year":2024,"journal":"BMC pharmacology & toxicology, 25(1), 64","doi":"10.1186/s40360-024-00789-9","pmid":"39267168","tags":["glp-1-agonists","weight-management","gut-health"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Stratified FAERS analysis revealed distinct digestive adverse event profiles across anti-obesity medication classes, providing the first comprehensive cascading analysis of GI safety for weight loss drugs including GLP-1 agonists.","whyItMatters":"GI side effects are the most common reason patients discontinue anti-obesity medications. A comparative analysis across drug classes helps clinicians choose the best option for patients with existing digestive conditions or GI sensitivity.","specificNumbers":"Comprehensive FAERS analysis across multiple anti-obesity drug classes. Stratified by specific digestive adverse event types.","methodology":"Real-world pharmacovigilance study using the FDA Adverse Event Reporting System (FAERS). Stratified analysis of digestive system adverse events across all classes of anti-obesity medications with cascading comparison.","limitations":"FAERS data is voluntary and subject to reporting bias. Cannot establish causation. Different drugs have different market penetration and reporting awareness. Time periods of availability differ across drug classes."},{"rthcId":"RPEP-09589","title":"Tirzepatide shows neuroprotective effects via regulating brain glucose metabolism in APP/PS1 mice.","authors":"Yang, Shaobin; Zhao, Xiaoqian; Zhang, Yimeng; Tang, Qi; Li, Yanhong; Du, Yaqin; Yu, Peng","year":2024,"journal":"Peptides, 179, 171271","doi":"10.1016/j.peptides.2024.171271","pmid":"39002758","tags":["tirzepatide","glp-1-agonists","neurological-conditions"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Tirzepatide (10 nmol/kg, once weekly for 8 weeks) showed neuroprotective effects in APP/PS1 Alzheimer's mice by regulating brain glucose metabolism, demonstrating the therapeutic potential of dual GLP-1/GIP receptor agonism for neurodegeneration.","whyItMatters":"Alzheimer's disease has almost no effective treatments. If tirzepatide can restore brain glucose metabolism — a fundamental deficiency in AD — it could slow disease progression. The dual GLP-1/GIP activation may provide greater brain benefits than single-receptor drugs.","specificNumbers":"10 nmol/kg tirzepatide once-weekly for 8 weeks. Significant improvements in learning and memory tests in APP/PS1 mice.","methodology":"APP/PS1 transgenic Alzheimer's disease model mice treated with tirzepatide (10 nmol/kg i.p., once weekly, 8 weeks). Brain glucose metabolism assessed alongside neuroprotective markers.","limitations":"APP/PS1 mice don't fully replicate human Alzheimer's disease. The specific molecular pathways between dual receptor activation and glucose metabolism improvement weren't fully defined. Only one dose was tested. Translation to human AD treatment is uncertain."},{"rthcId":"RPEP-09590","title":"Real world study of GLP-1 receptor agonists in overweight or obese type 2 diabetes by using repeated measurement analysis of variance.","authors":"Yang, Wanying; Zhou, Xiangming; Miao, Yuanyuan; Wang, Lu; Zhao, Yunhui; Ke, Tingyu; Ban, Lili","year":2024,"journal":"Medicine, 103(32), e38879","doi":"10.1097/MD.0000000000038879","pmid":"39121301","tags":["semaglutide","glp-1-agonists","metabolic-health"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"GLP-1 receptor agonists combined with metformin produced statistically significant improvements in HbA1c, fasting glucose, and BMI at 6 and 12 months compared to metformin alone, with comparable safety profiles.","whyItMatters":"Most type 2 diabetes patients begin treatment with metformin alone. This real-world evidence supports adding GLP-1 drugs earlier in treatment for overweight patients, showing meaningful improvements in both blood sugar and weight that persist over a year.","specificNumbers":"Outcomes measured at baseline, 3 months, and 6 months. Significant improvements in HbA1c, fasting glucose, and BMI with combination therapy.","methodology":"Real-world cohort study comparing metformin alone (n=35) versus metformin plus dulaglutide or semaglutide (n=32) in overweight/obese type 2 diabetes patients from July 2021 to June 2022, using repeated measures ANOVA.","limitations":"Small sample size (67 total). Non-randomized real-world design. Dulaglutide and semaglutide were grouped together rather than compared separately. Metformin dosing may have varied. Single-center study limits generalizability."},{"rthcId":"RPEP-09591","title":"Weight reduction and the risk of gallbladder and biliary disease: A systematic review and meta-analysis of randomized clinical trials.","authors":"Yang, Wenjia; Wu, Han; Cai, Xiaoling; Lin, Chu; Luo, Yingying; Hu, Suiyuan; Li, Zonglin; Jiao, Ruoyang; Bai, Shuzhen; Liu, Geling; Yang, Xiaolin; Ji, Linong","year":2024,"journal":"Obesity reviews : an official journal of the International Association for the Study of Obesity, 25(6), e13725","doi":"10.1111/obr.13725","pmid":"38346789","tags":["glp-1-agonists","weight-management"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Weight management strategies were associated with a 36% increased risk of gallbladder/biliary disease (OR 1.361, 95% CI 1.147-1.614), including increased risks of gallstones, cholecystitis, and cholecystectomy. GLP-1 receptor agonists specifically showed elevated risk.","whyItMatters":"As potent GLP-1 drugs produce larger weight losses in more patients, gallbladder complications may become a growing clinical concern. This meta-analysis quantifies the risk and highlights the need for monitoring, especially with higher-dose treatments.","specificNumbers":"RCTs with ≥12-week duration included. Significant increase in gallbladder/biliary events with weight loss. Risk proportional to weight reduction magnitude.","methodology":"Systematic review and meta-analysis of randomized controlled trials with at least 12 weeks duration comparing anti-obesity medications to placebo or bariatric surgery to less intensive weight management strategies.","limitations":"Some included trials had short follow-up. Individual risk factors for gallbladder disease (age, sex, baseline BMI) were not fully disaggregated. Different weight loss mechanisms may carry different risk profiles. Could not determine optimal monitoring strategies."},{"rthcId":"RPEP-09592","title":"Clinical Pharmacokinetics of Semaglutide: A Systematic Review.","authors":"Yang, Xi-Ding; Yang, Yong-Yu","year":2024,"journal":"Drug design, development and therapy, 18, 2555-2570","doi":"10.2147/DDDT.S470826","pmid":"38952487","tags":["semaglutide","glp-1-agonists","drug-delivery"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Semaglutide has a predictable pharmacokinetic profile with a long half-life supporting once-weekly subcutaneous dosing. Oral semaglutide exposure is affected by food and dosing conditions, but neither form requires dose adjustment for renal or hepatic impairment.","whyItMatters":"Understanding semaglutide's pharmacokinetics helps clinicians optimize dosing, counsel patients on proper oral administration, and predict how the drug will behave in patients with different body weights or organ impairment.","specificNumbers":"Subcutaneous: ~1 week half-life, 1-3 day Tmax. Oral: ~1% bioavailability, requires fasting. Population PK parameters across multiple subgroups.","methodology":"Systematic review of 17 studies from PubMed and Embase reporting semaglutide pharmacokinetic parameters (AUC, Cmax, time to Cmax, half-life, and clearance) in healthy and diseased populations.","limitations":"Limited data on the effect of body weight on exposure. Pharmacokinetic studies may not capture real-world variability in absorption. Oral semaglutide data is more limited than subcutaneous. Does not address pharmacokinetics of higher doses used for weight management."},{"rthcId":"RPEP-09593","title":"Mechanism of Peptide Self-assembly and Its Study in Biomedicine.","authors":"Yang, Xinyue; Ma, Li; Lu, Kui; Zhao, Dongxin","year":2024,"journal":"The protein journal, 43(3), 464-476","doi":"10.1007/s10930-024-10200-5","pmid":"38676873","tags":["bioactive-peptides","peptide-chemistry"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Peptide self-assembly is driven by hydrogen bonding, hydrophobic interactions, electrostatic forces, and π-π stacking, producing diverse nanostructures with broad biomedical applications including drug delivery systems and hydrogels.","whyItMatters":"Self-assembling peptides represent a growing platform for drug delivery and regenerative medicine. Understanding the assembly mechanisms helps researchers design better peptide-based therapeutics and biomaterials.","specificNumbers":"Four main assembly forces reviewed. Applications spanning drug delivery, tissue engineering, wound healing, and biosensing.","methodology":"Narrative review covering the mechanisms, classifications, and biomedical applications of peptide self-assembly, with focus on hydrogel formation.","limitations":"Review article providing a broad overview rather than systematic analysis. Limited discussion of clinical translation challenges such as scalability, stability, and regulatory pathways. Does not quantify efficacy of specific applications."},{"rthcId":"RPEP-09594","title":"Comparison of changes in adipokine and inflammatory cytokine levels in patients with newly diagnosed type 2 diabetes treated with exenatide, insulin, or pioglitazone: A post-hoc study of the CONFIDENCE trial.","authors":"Yang, Xubin; Deng, Hongrong; Lv, Jing; Chen, Xueyan; Zeng, Longyi; Weng, Jianping; Liang, Hua; Xu, Wen","year":2024,"journal":"Heliyon, 10(1), e23309","doi":"10.1016/j.heliyon.2023.e23309","pmid":"38169889","tags":["exenatide","glp-1-agonists","inflammation","metabolic-health"],"studyType":"RCT","evidenceStrength":"moderate","keyFinding":"Exenatide significantly decreased IL-1β and IFN-γ levels over 48 weeks, while insulin increased both markers. The anti-inflammatory effect of exenatide was independent of changes in weight, waist circumference, and HbA1c, and was associated with improved insulin resistance.","whyItMatters":"Chronic low-grade inflammation drives many complications of type 2 diabetes. This large RCT shows that exenatide has anti-inflammatory properties beyond blood sugar control — a benefit that insulin and pioglitazone do not share, potentially favoring GLP-1 drugs as first-line therapy.","specificNumbers":"416 patients from 25 centers. 48-week intervention. Three treatment arms compared for adipokine and inflammatory cytokine changes.","methodology":"Post-hoc analysis of the CONFIDENCE trial: 416 newly diagnosed T2DM patients from 25 centers randomized to 48-week treatment with exenatide, insulin, or pioglitazone. Adipokines (leptin, FGF21) and inflammatory cytokines (IL-1β, IFN-γ) measured at baseline and study end.","limitations":"Post-hoc analysis — adipokine changes were not the primary trial endpoint. Chinese population only, limiting generalizability. Exenatide is an older, less potent GLP-1 agonist; newer drugs like semaglutide may show different patterns. 32% dropout rate over 48 weeks."},{"rthcId":"RPEP-09595","title":"First real-world study on the effectiveness and tolerability of rimegepant for acute migraine therapy in Chinese patients.","authors":"Yang, Zhao; Wang, Xiaodan; Niu, Mengyue; Wei, Qiao; Zhong, Huizhu; Li, Xiaoyan; Yuan, Weihong; Xu, Wenli; Zhu, Shuo; Yu, Shengyuan; Liu, Jun; Yan, Jianzhou; Kang, Wenyan; Huang, Peijian","year":2024,"journal":"The journal of headache and pain, 25(1), 160","doi":"10.1186/s10194-024-01873-5","pmid":"39333875","tags":["CGRP-peptides","neurological-conditions"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Rimegepant significantly reduced moderate-to-severe migraine pain and improved functional ability in Chinese patients, with effectiveness observed as early as 30 minutes and sustained through 48 hours. Only 6% experienced mild adverse events.","whyItMatters":"Most rimegepant clinical data comes from Western populations. This first prospective real-world study in Chinese patients confirms the drug's effectiveness and tolerability in an East Asian population, supporting its broader global use.","specificNumbers":"This was a prospective real-world study — specific response rates were measured but the abstract focuses on the study design as a first-of-its-kind investigation.","methodology":"Single-arm, prospective, real-world study of 133 enrolled participants (99 analyzed). Patients self-reported pain intensity, functional ability, and symptoms at predose and 0.5, 1, 2, 24, and 48 hours postdose via digital platform. Subgroups included prior nonresponders (n=30) and rimegepant+eptinezumab combination (n=23).","limitations":"Single-arm design with no placebo control. Single attack evaluated per patient. Relatively small sample size. Self-reported outcomes may introduce bias. Registered retrospectively on ClinicalTrials.gov."},{"rthcId":"RPEP-09596","title":"Biodirected Screening and Preparation of Larimichthys crocea Angiotensin-I-Converting Enzyme-Inhibitory Peptides by a Combined In Vitro and In Silico Approach.","authors":"Yang, Zhizhi; Wang, Changrong; Huang, Baote; Chen, Yihui; Liu, Zhiyu; Chen, Hongbin; Chen, Jicheng","year":2024,"journal":"Molecules (Basel, Switzerland), 29(5)","doi":"10.3390/molecules29051134","pmid":"38474646","tags":["bioactive-peptides","cardiovascular-health"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Six novel ACE-inhibitory peptides were identified from yellow croaker protein with IC50 values ranging from 0.63 to 10.26 μM. Three peptides (IPYADFK, FYEPFM, NWPWMK) maintained activity after simulated gastrointestinal digestion.","whyItMatters":"Finding potent natural ACE inhibitors from food sources could lead to functional foods or nutraceuticals that help manage blood pressure with fewer side effects than pharmaceutical drugs.","specificNumbers":"Multiple ACE-inhibitory peptides were identified from Larimichthys crocea protein using the combined computational and experimental pipeline.","methodology":"Combined in silico hydrolysis, QSAR modeling, LC-MS/MS identification, inhibition kinetics, and molecular docking to screen, identify, and validate ACE-inhibitory peptides from Larimichthys crocea protein.","limitations":"In vitro and in silico study only — no animal or human testing. Gastrointestinal simulation may not fully replicate real digestion. Bioavailability after absorption is unknown. Practical application as food product not yet developed."},{"rthcId":"RPEP-09597","title":"Marine peptides as potential anti-aging agents: Preparation, characterization, mechanisms of action, and future perspectives.","authors":"Yao, Wanzi; Zhang, Yifeng; Zhang, Gaiping","year":2024,"journal":"Food chemistry, 460(Pt 1), 140413","doi":"10.1016/j.foodchem.2024.140413","pmid":"39033641","tags":["bioactive-peptides","anti-aging","collagen-peptides"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Marine peptides target multiple aging mechanisms simultaneously — oxidative stress reduction, inflammation modulation, mitochondrial repair, autophagy induction, and longevity pathway regulation — making them promising multi-target anti-aging agents.","whyItMatters":"As the global population ages, finding safe, natural compounds that target multiple aging pathways is increasingly important. Marine peptides offer a largely untapped reservoir of bioactive molecules that could complement existing anti-aging strategies.","specificNumbers":"The review covers multiple marine sources and preparation methods, synthesizing evidence from numerous studies on anti-aging mechanisms.","methodology":"Narrative review examining the sources, preparation methods, physicochemical properties, and anti-aging mechanisms of marine-derived peptides.","limitations":"Review article without systematic methodology. Most evidence from in vitro and animal studies. Challenges of stability, bioavailability, and scalability not fully addressed. Clinical human data largely absent."},{"rthcId":"RPEP-09598","title":"Research Progress of Food-Derived Antihypertensive Peptides in Regulating the Key Factors of the Renin-Angiotensin System.","authors":"Yao, Xinyu; Cao, Xinyi; Chen, Liang; Liao, Wang","year":2024,"journal":"Nutrients, 17(1)","doi":"10.3390/nu17010097","pmid":"39796531","tags":["bioactive-peptides","cardiovascular-health"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Food-derived antihypertensive peptides target at least four key points in the renin-angiotensin system: ACE inhibition (most studied), renin inhibition, AT1 receptor blockade/downregulation, and ACE2 activation — offering multi-target blood pressure management potential.","whyItMatters":"Hypertension affects over a billion people worldwide. Food-derived peptides could offer a safer, more natural complement or alternative to pharmaceutical blood pressure drugs, with fewer side effects and the potential for multi-target activity.","specificNumbers":"Review covers the full renin-angiotensin system pathway and emerging AI methods for peptide identification from food proteins.","methodology":"Narrative review summarizing research on food protein-derived antihypertensive peptides, organized by their mechanisms of action within the renin-angiotensin system.","limitations":"Narrative review without systematic methodology. Most antihypertensive peptides tested only in vitro or animal models. Bioavailability and clinical efficacy in humans remain largely unproven. Regulatory pathway for food-derived peptide health claims is unclear."},{"rthcId":"RPEP-09599","title":"Exploring the antioxidant properties of semaglutide: A comprehensive review.","authors":"Yaribeygi, Habib; Maleki, Mina; Forouzanmehr, Behina; Kesharwani, Prashant; Jamialahmadi, Tannaz; Karav, Sercan; Sahebkar, Amirhossein","year":2024,"journal":"Journal of diabetes and its complications, 38(12), 108906","doi":"10.1016/j.jdiacomp.2024.108906","pmid":"39549371","tags":["GLP-1-receptor-agonists","semaglutide","oxidative-stress"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Semaglutide demonstrates antioxidant properties through multiple molecular pathways, suggesting its clinical benefits in diabetes extend beyond glucose lowering to include direct protection against oxidative damage in various tissues.","whyItMatters":"If semaglutide fights both hyperglycemia and oxidative stress simultaneously, it provides dual protection against diabetic complications — a benefit that many traditional diabetes drugs do not offer. This may partly explain the drug's cardiovascular and renal benefits seen in large clinical trials.","specificNumbers":"Review covers multiple studies demonstrating semaglutide's antioxidant effects across various tissues and disease models.","methodology":"Comprehensive narrative review of published preclinical and clinical studies examining semaglutide's antioxidant mechanisms and their potential clinical significance.","limitations":"Most antioxidant evidence comes from animal and cell studies. The relative contribution of antioxidant effects versus other mechanisms to clinical outcomes in humans is unclear. Exact molecular pathways still being elucidated."},{"rthcId":"RPEP-09600","title":"Suppression of B-type natriuretic peptide gene expression in cardiomyocytes under anoxic conditions.","authors":"Yasutake, Rei; Nagoshi, Tomohisa; Yoshii, Akira; Takahashi, Hirotake; Oi, Yuhei; Kimura, Haruka; Kashiwagi, Yusuke; Tanaka, Toshikazu D; Tanaka, Yoshiro; Yoshimura, Michihiro","year":2024,"journal":"Peptides, 182, 171316","doi":"10.1016/j.peptides.2024.171316","pmid":"39490746","tags":["cardiovascular-health","natriuretic-peptides"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"BNP mRNA levels were substantially reduced in cardiomyocytes after 8+ hours of complete anoxia (95% N₂/5% CO₂), contrasting with the increase seen under hypoxia. Reoxygenation restored and significantly increased BNP expression by 24 hours, in an NHE1-dependent manner.","whyItMatters":"BNP is used clinically to assess heart failure severity. This finding reveals that in the most severely oxygen-deprived areas of a heart attack, BNP may actually be suppressed — meaning clinicians might underestimate cardiac damage if relying solely on BNP levels.","specificNumbers":"BNP mRNA levels were substantially reduced after exposure to 95% N2/5% CO2 anoxic conditions in neonatal rat cardiomyocytes.","methodology":"In vitro study exposing neonatal rat cardiomyocytes to anoxia (95% N₂/5% CO₂ airtight chamber) and measuring BNP mRNA levels at multiple time points, with NHE1 pathway modulation using aldosterone and NHE1 inhibitors.","limitations":"Used neonatal rat cardiomyocytes, which may differ from adult human heart cells. In vitro anoxia conditions may not perfectly replicate in vivo cardiac ischemia. Single-cell-type study does not account for the complex cardiac microenvironment."},{"rthcId":"RPEP-09601","title":"Reprint of: Impact of a pharmacist-led weight management service in a cardiology clinic.","authors":"Yates, Madison; Supple, Megan; Maccia, Melissa","year":2024,"journal":"Journal of the American Pharmacists Association : JAPhA, 64(4S), 102157","doi":"10.1016/j.japh.2024.102157","pmid":"39127937","tags":["GLP-1-receptor-agonists","weight-management","cardiovascular-health"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"100% of 31 completers achieved ≥5% weight loss at 6 months, with mean weight loss of 12.6%. Cardiometabolic markers also improved: HbA1c -0.6%, LDL -18 mg/dL, triglycerides -29 mg/dL, systolic BP -9 mmHg.","whyItMatters":"Cardiology patients with obesity face compounded cardiovascular risk. This study shows that pharmacist-led GLP-1 management can deliver meaningful weight loss plus improvements in multiple cardiac risk factors — a model that could expand access to these treatments.","specificNumbers":"The study evaluated outcomes from a pharmacist-managed service using GLP-1 RAs in a cardiology clinic population.","methodology":"Single-center, prospective, pre-post analysis of adults with BMI ≥30 (or ≥27 with comorbidity) managed by a clinical pharmacist using GLP-1 RAs (semaglutide or liraglutide) with lifestyle counseling in a cardiology clinic, March 2022 to March 2023.","limitations":"No control group — cannot separate drug effects from pharmacist intervention and lifestyle changes. High dropout: only 31 of 59 starters completed 6 months. Single-center study. Selection bias from insurance coverage requirement (only patients with coverage for Wegovy/Saxenda)."},{"rthcId":"RPEP-09602","title":"Structure-Based Design of Bicyclic Helical Peptides That Target the Oncogene β-Catenin.","authors":"Yeste-Vázquez, Alejandro; Paulussen, Felix M; Wendt, Mathias; Klintrot, Rasmus; Schulte, Clemens; Wallraven, Kerstin; van Gijzel, Lieke; Simeonov, Boris; van der Gaag, Maurice; Gerber, Alan; Maric, Hans M; Hennig, Sven; Grossmann, Tom N","year":2024,"journal":"Angewandte Chemie (International ed. in English), 63(47), e202411749","doi":"10.1002/anie.202411749","pmid":"39167026","tags":["peptide-drug-design","cancer-research"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"A bicyclic stitched peptide with unprecedented crosslink architecture was designed to bind β-catenin, with the binding mode confirmed by crystal structure and cell-based activity reaching single-digit micromolar inhibition.","whyItMatters":"β-catenin is implicated in colorectal, breast, liver, and many other cancers but has resisted drug development for decades. These smaller peptide inhibitors represent a potential breakthrough for targeting this challenging oncogene.","specificNumbers":"The bicyclic peptides are considerably smaller than previous β-catenin inhibitors while maintaining high binding affinity.","methodology":"Structure-based design starting from the Axin α-helical binding motif, followed by sequence maturation, bicyclization with novel crosslink architecture, X-ray crystallography to confirm binding, and cell-based assay validation.","limitations":"Early-stage drug design — demonstrated binding and cell-based activity but no in vivo testing. Cell penetration and metabolic stability need further optimization. Single-digit micromolar potency may need improvement for therapeutic use."},{"rthcId":"RPEP-09603","title":"Liraglutide ameliorates diabetic kidney disease by modulating gut microbiota and L-5-Oxoproline.","authors":"Yi, Bo; Su, Ke; Cai, Yu-Li; Chen, Xiao-Ling; Bao, Yan; Wen, Zhong-Yuan","year":2024,"journal":"European journal of pharmacology, 983, 176905","doi":"10.1016/j.ejphar.2024.176905","pmid":"39154828","tags":["GLP-1-receptor-agonists","liraglutide","kidney-function","gut-health"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Liraglutide improved gut microbiota diversity (increased Simpson index, P=0.035), boosted beneficial bacteria like Clostridium and Oscillospira, increased serum L-5-Oxoproline, and reduced ectopic lipid deposition in kidney tubules through SREBP1/FAS pathway suppression.","whyItMatters":"Diabetic kidney disease is the leading cause of kidney failure worldwide. This study reveals a novel gut-kidney axis mechanism for liraglutide's renoprotective effects, opening potential new therapeutic strategies targeting gut microbiota and metabolites.","specificNumbers":"Liraglutide decreased serum L-5-Oxoproline levels and reduced ectopic lipid deposition in renal tubules of diabetic rats.","methodology":"Diabetic kidney disease rat model (Sprague-Dawley rats on high-fat diet + streptozotocin + uninephrectomy) treated with liraglutide 0.4 mg/kg/day. Multi-omics analysis of gut microbiome, serum metabolites, and kidney pathology. In vitro validation with HK-2 kidney cells exposed to high glucose/palmitate and L-5-Oxoproline.","limitations":"Animal study — gut microbiome and metabolite responses may differ in humans. The DKD rat model (high-fat diet + STZ + nephrectomy) is artificial. Specific bacterial strains responsible for 5-OP production were not definitively identified. No human clinical validation."},{"rthcId":"RPEP-09604","title":"Intranasal oxytocin as a treatment for anxiety and autism: From subclinical to clinical applications.","authors":"Yin, Hailian; Jiang, Meiyun; Han, Tao; Xu, Xiaolei","year":2024,"journal":"Peptides, 176, 171211","doi":"10.1016/j.peptides.2024.171211","pmid":"38579916","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09605","title":"Thymosin β4 Regulates the Differentiation of Thymocytes by Controlling the Cytoskeletal Rearrangement and Mitochondrial Transfer of Thymus Epithelial Cells.","authors":"Ying, Yuyuan; Tao, Nana; Zhang, Fengjie; Wen, Xunuo; Zhou, Meiru; Gao, Jianli","year":2024,"journal":"International journal of molecular sciences, 25(2)","doi":"10.3390/ijms25021088","pmid":"38256161","tags":["thymosin-beta-4","immune-function"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Thymosin β4 primarily regulates microfilament formation and mitochondrial transfer in thymic epithelial cells, influencing the differentiation of double-negative (CD4⁻CD8⁻) and CD4 single-positive (CD3⁺TCRβ⁺CD4⁺CD8⁻) thymocytes through F-actin aggregation.","whyItMatters":"Understanding how thymosin β4 controls thymus function could lead to therapies that slow or reverse age-related thymic shrinkage, potentially rejuvenating the aging immune system and improving T cell production in elderly individuals.","specificNumbers":"The study demonstrated that Thymosin β4 regulated both cytoskeletal dynamics and mitochondrial transfer in TECs to support thymocyte differentiation.","methodology":"In vitro study using H&E staining, immunofluorescence, transmission electron microscopy, RT-qPCR, flow cytometry, cytoskeletal immunolabeling, and mitochondrial immunolabeling to assess Tβ4's effects on thymic epithelial cell structure and thymocyte development.","limitations":"In vitro study — the complex thymic microenvironment in living organisms may produce different results. The exact signaling pathway from Tβ4 to F-actin to mitochondrial transfer needs further elucidation. No in vivo aging model tested."},{"rthcId":"RPEP-09606","title":"Clinical Efficacy and Safety of Anti-Obesity Medications Among Adult East Asian People with Obesity: A Systematic Literature Review and Indirect Treatment Comparison.","authors":"Yokote, Koutaro; Ota, Riku; Wada, Shogo; Matsuda, Hiroyuki; Filomeno, Ronald","year":2024,"journal":"Advances in therapy, 41(9), 3452-3470","doi":"10.1007/s12325-024-02941-7","pmid":"39039386","tags":["GLP-1-receptor-agonists","weight-management","tirzepatide"],"studyType":"meta-analysis","evidenceStrength":"moderate","keyFinding":"Semaglutide (STEP 6) significantly reduced body weight and cardiometabolic risk factors (HbA1c, cholesterol, blood pressure) in Japanese and South Korean patients with obesity. Mazindol also reduced weight and cholesterol in Japan. Direct comparison was not feasible due to study heterogeneity.","whyItMatters":"East Asians face higher obesity-related health risks at lower BMI levels than Western populations, making effective anti-obesity treatments particularly important in this group. This review establishes the evidence base for the two most relevant medications.","specificNumbers":"Asians have higher obesity-related comorbidity risk at lower BMI compared to Europeans; the review highlights this disparity in available drug evidence.","methodology":"Systematic literature review of Embase, MEDLINE, and ICHUSHI databases for RCTs of semaglutide or mazindol in East Asian adults with obesity. Indirect treatment comparison (ITC) feasibility was assessed based on heterogeneity of effect modifiers and study design variations.","limitations":"Only 2 studies met inclusion criteria, severely limiting analysis. Semaglutide and mazindol could not be directly compared. English and Japanese language restriction may have excluded some studies. No data on newer GLP-1 agonists (tirzepatide) in East Asian populations at time of review."},{"rthcId":"RPEP-09607","title":"Efficacy and safety of switching from a dipeptidyl peptidase-4 inhibitor to oral semaglutide in Japanese patients with type 2 diabetes mellitus.","authors":"Yoneda, Chihiro; Kobayashi, Junji; Kuribayashi, Nobuichi","year":2024,"journal":"Diabetology international, 15(3), 569-576","doi":"10.1007/s13340-024-00734-5","pmid":"39101186","tags":["GLP-1-receptor-agonists","semaglutide","diabetes"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Switching from DPP-4i to oral semaglutide reduced mean HbA1c from 7.8% to 7.0% (P significant) and decreased body weight (P significant). 95.6% improved in either HbA1c or weight. Greater HbA1c reduction correlated with greater weight loss (r=0.480, P<0.001). 20% discontinued within 6 months.","whyItMatters":"DPP-4 inhibitors are the backbone of Japanese diabetes treatment but often provide insufficient control. This study shows oral semaglutide can be a practical step-up that improves both blood sugar and weight without requiring injections.","specificNumbers":"68 Japanese patients were studied after switching from DPP-4 inhibitors to oral semaglutide, with improvements in both HbA1c and body weight.","methodology":"Single-center retrospective study of 68 Japanese T2D patients switched from DPP-4 inhibitors to oral semaglutide for ≥6 months without changes to other oral hypoglycemics. Outcomes: HbA1c and body weight changes.","limitations":"Retrospective, single-center, no control group. Cannot separate drug switch effect from regression to mean. 20% dropout introduces survival bias. No long-term follow-up beyond 6 months. Non-obese older patients had highest discontinuation, suggesting limited utility in this subgroup."},{"rthcId":"RPEP-09608","title":"Effects of exposure to the neonicotinoid pesticide clothianidin on α-defensin secretion and gut microbiota in mice.","authors":"Yonoichi, Sakura; Hara, Yukako; Ishida, Yuya; Shoda, Asuka; Kimura, Mako; Murata, Midori; Nunobiki, Sarika; Ito, Makiko; Yoshimoto, Ayano; Mantani, Youhei; Yokoyama, Toshifumi; Hirano, Tetsushi; Ikenaka, Yoshinori; Yokoi, Yuki; Ayabe, Tokiyoshi; Nakamura, Kiminori; Hoshi, Nobuhiko","year":2024,"journal":"The Journal of veterinary medical science, 86(3), 277-284","doi":"10.1292/jvms.23-0514","pmid":"38267031","tags":["bioactive-peptides","gut-health","immune-function"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Clothianidin exposure suppressed α-defensin (Crp1) secretion from Paneth cells in mice, leading to reduced fecal and cecal Crp1 levels, gut dysbiosis, and loss of short-chain fatty acid-producing bacteria. The suppression occurred at the secretion level, not the production level.","whyItMatters":"Neonicotinoids are among the most widely used pesticides globally, and residues are found in common foods. If they suppress gut defensin secretion in humans as well, this could contribute to gut microbiome disruption and associated health problems in the general population.","specificNumbers":"Cryptdin-1 (Crp1, a major mouse α-defensin) levels were significantly lower in feces and cecal contents of clothianidin-exposed mice compared to controls.","methodology":"Subchronic clothianidin exposure in mice with immunostaining of Paneth cells (jejunum and ileum), measurement of fecal and cecal cryptdin-1 levels, and 16S rRNA sequencing of gut microbiota composition.","limitations":"Mouse study — mouse defensins (cryptdins) differ structurally from human α-defensins (HD5, HD6). Exposure levels may not match typical human dietary intake. Mechanism of secretion suppression not fully elucidated. No human epidemiological data to confirm relevance."},{"rthcId":"RPEP-09609","title":"The coming of age of cyclic peptide drugs: an update on discovery technologies.","authors":"You, Sophia; McIntyre, Glen; Passioura, Toby","year":2024,"journal":"Expert opinion on drug discovery, 19(8), 961-973","doi":"10.1080/17460441.2024.2367024","pmid":"38872502","tags":["drug-discovery","peptide-engineering"],"studyType":"review","evidenceStrength":"n/a-review","keyFinding":"Cyclic peptide drug discovery has reached a turning point. For decades, cyclic peptide drugs came almost exclusively from natural products (compounds found in nature). But in recent years, display screening technologies — particularly phage display and mRNA display — have matured enough that the first de novo (designed-from-scratch) cyclic peptide drugs discovered through these methods have reached the market.\n\nCyclic peptides occupy a unique therapeutic sweet spot: they can hit a broader range of protein targets than traditional small-molecule drugs, while also being potentially capable of oral availability and cell penetration — two properties that most peptide drugs lack. However, significant technical challenges remain, particularly in engineering membrane permeability and oral bioavailability for intracellular targets.","whyItMatters":"Most peptide drugs require injection, which limits their use. Cyclic peptides — peptides bent into a ring shape — have the rare potential to be taken as pills and to enter cells. This review documents a major milestone: the field has moved from purely academic to producing FDA-approved drugs from display screening, marking cyclic peptides as one of the most promising frontiers in pharmaceutical development.","specificNumbers":"Two decades of display technology development · First de novo display-derived cyclic peptides reaching market · Many more in clinical trials · Broader target range than small molecules","methodology":"Expert review article surveying the clinical landscape for cyclic peptide drugs, comparing natural product-derived versus display-derived discovery approaches, and assessing the technical challenges remaining in the field.","limitations":"As a review, no new experimental data is presented. The assessment of the field's maturity and remaining challenges reflects the authors' expert perspective. Specific clinical pipeline data may have changed since publication."},{"rthcId":"RPEP-09610","title":"Treatment Outcome After Switching From Galcanezumab to Fremanezumab in Patients With Migraine.","authors":"Youn, Michelle Sojung; Kim, Namoh; Lee, Mi Ji; Kim, Manho","year":2024,"journal":"Journal of clinical neurology (Seoul, Korea), 20(3), 300-305","doi":"10.3988/jcn.2023.0311","pmid":"38713076","tags":["CGRP-peptides","neurological-conditions"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Among galcanezumab non-responders, 71.4% achieved a treatment response after switching to fremanezumab, demonstrating that response to one anti-CGRP antibody is independent of response to another.","whyItMatters":"Many migraine patients give up on CGRP antibodies after failing one. This study suggests switching to a different CGRP antibody — even one targeting the same molecule — can still provide relief, offering a simpler treatment step before changing drug classes entirely.","specificNumbers":"The study tracked outcomes for patients switched between the two CGRP-targeting monoclonal antibodies.","methodology":"Prospective registry-based cohort study at a single university hospital, tracking patients who received galcanezumab for at least 3 months before switching to fremanezumab for another 3+ months. Response was defined as a 50% or greater reduction in moderate-to-severe headache days.","limitations":"Very small sample size (21 patients) from a single center. No control group or blinding, so placebo effects and natural disease fluctuation cannot be ruled out. Only studied switching in one direction (galcanezumab to fremanezumab)."},{"rthcId":"RPEP-09611","title":"Development of stapled NONO-associated peptides reveals unexpected cell permeability and nuclear localisation.","authors":"Young, Reginald; Huang, Tiancheng; Luo, Zijie; Tan, Yaw Sing; Kaur, Amandeep; Lau, Yu Heng","year":2024,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 30(5), e3562","doi":"10.1002/psc.3562","pmid":"38148630","tags":["peptide-drug-design","cancer-research"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Stapled peptides derived from IGFBP-3 and NONO dimerization sequences demonstrated unexpected cell permeability and preferential nuclear localization, despite only modest binding affinity to the NONO dimer.","whyItMatters":"Cell permeability and nuclear targeting are two of the biggest hurdles in peptide drug development. Finding peptides that achieve both naturally opens a new path for designing drugs against nuclear cancer targets like NONO.","specificNumbers":"Stapled peptides achieved both cell penetration and nuclear localization — properties rarely seen together in designed peptides.","methodology":"In vitro study using multiple peptide stapling chemistries (Pd-catalyzed cross-coupling, cysteine arylation, cysteine alkylation) to create macrocyclic helical peptides. Cell permeability and nuclear localization assessed via live confocal microscopy with dye-labeled peptides.","limitations":"NONO binding was modest and could not be saturated. No functional anticancer activity demonstrated. Only tested in cell culture — no animal or clinical data. Nuclear localization mechanism not fully understood."},{"rthcId":"RPEP-09612","title":"Molecular farming expression of recombinant fusion proteins applied to skincare strategies.","authors":"Yu, Guangdong; Zhao, Wengang; Wang, Yunpeng; Xu, Nuo","year":2024,"journal":"PeerJ, 12, e17957","doi":"10.7717/peerj.17957","pmid":"39308805","tags":["bioactive-peptides","collagen-peptides"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Fusing EGF with cell-penetrating peptides in plant expression systems is a feasible strategy for producing transdermal skincare proteins, though clinical efficacy data is still lacking.","whyItMatters":"Bioactive peptides for skincare are expensive to manufacture. Plant-based production could make effective peptide skincare products more affordable and accessible while also being more environmentally sustainable.","specificNumbers":"Review covers multiple expression strategies in Arabidopsis thaliana for producing skincare-relevant fusion proteins.","methodology":"Narrative literature review examining molecular farming expression strategies, fusion protein design combining EGF with cell-penetrating peptides, and transdermal delivery approaches for skincare.","limitations":"This is a review with no original experimental data. Most discussed applications are theoretical or at early research stages. Plant-to-commercial scaling challenges are acknowledged but not resolved. Clinical data on skin effects of plant-produced fusion proteins is essentially nonexistent."},{"rthcId":"RPEP-09613","title":"PD-1 inhibitor combined with SBRT, GM-CSF, and thymosin alpha-1 in metastatic breast cancer: A case report and literature review.","authors":"Yu, Jiamin; Wang, Qiang; Wang, Lijun; Zong, Dan; He, Xia","year":2024,"journal":"Medicine, 103(34), e39271","doi":"10.1097/MD.0000000000039271","pmid":"39183403","tags":["thymosin-alpha-1","immune-function","cancer-research"],"studyType":"case series","evidenceStrength":"preliminary","keyFinding":"The combination of PD-1 inhibitor, SBRT, GM-CSF, and thymosin alpha-1 produced a 78.97% regression in the target lesion and 56.73% regression in non-irradiated observed lesions (abscopal effect) in a patient with treatment-resistant mTNBC.","whyItMatters":"Triple-negative breast cancer with metastases has very few effective treatment options. This case demonstrates that combining immune-boosting peptides like thymosin alpha-1 with immunotherapy and targeted radiation may overcome treatment resistance, especially through abscopal effects on distant tumors.","specificNumbers":"48-year-old female patient who had not responded to multiple lines of therapy including surgery, chemotherapy, and radiotherapy.","methodology":"Single case report from a clinical trial combining stereotactic body radiotherapy (SBRT), PD-1 inhibitor immunotherapy, GM-CSF, and thymosin alpha-1. Response assessed using RECIST v1.1 criteria after 2 treatment cycles.","limitations":"Single case report — the weakest form of clinical evidence. One dramatic response does not prove the regimen works for other patients. No control group, blinding, or statistical analysis possible. The clinical trial is ongoing and broader results are needed."},{"rthcId":"RPEP-09614","title":"ToxGIN: an In silico prediction model for peptide toxicity via graph isomorphism networks integrating peptide sequence and structure information.","authors":"Yu, Qiule; Zhang, Zhixing; Liu, Guixia; Li, Weihua; Tang, Yun","year":2024,"journal":"Briefings in bioinformatics, 25(6)","doi":"10.1093/bib/bbae583","pmid":"39530430","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09615","title":"Laser Acupuncture versus Liraglutide in Treatment of Obesity: A Multi-Institutional Retrospective Cohort Study.","authors":"Yu, Wen-Lin; Liao, Yu-Ning; Yang, Tsung-Hsien; Yang, Ching-Wei; Kao, Ting-I; Lee, Pai-Wei; Hsu, Chiu-Yi; Huang, Jhen-Ling; Huang, Yu-Tung; Chen, Hsing-Yu","year":2024,"journal":"Healthcare (Basel, Switzerland), 12(13)","doi":"10.3390/healthcare12131279","pmid":"38998814","tags":["GLP-1-receptor-agonists","liraglutide","weight-management"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Laser acupuncture users lost an average of 5.82 kg versus 2.38 kg with liraglutide over 180 days, with the difference remaining significant after adjusting for baseline differences.","whyItMatters":"GLP-1 receptor agonists like liraglutide are widely used for weight management, but not all patients respond well or tolerate side effects. Understanding how these peptide drugs compare to alternative approaches helps inform treatment decisions.","specificNumbers":"Data from 2013-2018 analyzed with primary outcomes measured at 180 days post-treatment.","methodology":"Multi-institutional retrospective cohort study using the Chang Gung Research Database (2013-2018). Compared 173 laser acupuncture users with 572 liraglutide users. Primary outcomes: body weight and BMI changes at 180 days. Secondary outcomes: proportion achieving 5%, 10%, and 15% weight loss. Statistical adjustments made for baseline differences.","limitations":"Retrospective design with significant self-selection bias — patients choosing acupuncture versus medication likely differ in motivation, lifestyle, and other factors. No randomization or blinding. Database study lacks detailed clinical context such as diet, exercise, and compliance. Liraglutide dosing details not specified. The liraglutide doses used (2013-2018) may not reflect current optimal protocols."},{"rthcId":"RPEP-09616","title":"Effect of glucagon-like peptide-1 receptor agonists on prostate cancer: A review.","authors":"Yu, Xu; Liu, Jie","year":2024,"journal":"Medicine, 103(41), e39956","doi":"10.1097/MD.0000000000039956","pmid":"39465848","tags":["GLP-1-receptor-agonists","cancer-research"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"GLP-1 receptors are expressed in prostate cancer tissue, and preclinical evidence suggests GLP-1 receptor agonists may inhibit prostate cancer growth, though clinical evidence is limited.","whyItMatters":"With millions of men now using GLP-1 peptide drugs for diabetes and weight loss, understanding whether these drugs influence prostate cancer risk is a critical safety and public health question — especially since prostate cancer is the most common cancer in men.","specificNumbers":"GLP-1R is widely expressed across various cell types and tissues, including prostate cells.","methodology":"Narrative literature review examining GLP-1 receptor expression in prostate cancer and the effects of GLP-1 receptor agonists on prostate cancer biology and clinical outcomes.","limitations":"Narrative review without systematic methodology or meta-analysis. Most evidence is preclinical (cell and animal studies). Observational cancer data is confounded by diabetes and obesity themselves being independent cancer risk factors. No randomized trial data specifically evaluating prostate cancer outcomes."},{"rthcId":"RPEP-09617","title":"Loss of Function of Vasoactive-intestinal Peptide Alters Sex Ratio and Reduces Male Reproductive Fitness in Zebrafish.","authors":"Yu, Yang; Tanaka, Sakura; Wong, Ten-Tsao; Zohar, Yonathan; Zmora, Nilli","year":2024,"journal":"Endocrinology, 165(8)","doi":"10.1210/endocr/bqae082","pmid":"38984720","tags":["VIP","neuropeptides","reproductive-health"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"VIPa knockout males had 70% fewer spermatids, 80% reduced fertilization capacity, 50% lower sperm motility, and near-absent sexual motivation due to downregulation of androgen synthesis enzymes and decreased 11-ketotestosterone production.","whyItMatters":"VIP exists in human testes too. Understanding its role in testosterone production and male fertility in animal models could eventually inform approaches to male infertility and hormonal regulation in humans.","specificNumbers":"vipa-/- males were severely subfertile, and offspring sex ratio was significantly female-biased.","methodology":"Gene knockout zebrafish model (vipa-/-) compared with wild-type males. Assessed testicular development, sperm count, fertilization rates, sperm motility, sexual behavior, gene expression of androgen synthesis enzymes, and hormone levels.","limitations":"Zebrafish reproduction differs significantly from mammalian reproduction — zebrafish have external fertilization and different sex determination mechanisms. VIP roles may not translate directly to humans. The knockout eliminates VIP entirely, which differs from more subtle variations that might occur naturally."},{"rthcId":"RPEP-09618","title":"Molecular dynamics-guided optimization of BGM0504 enhances dual-target agonism for combating diabetes and obesity.","authors":"Yuan, Jiandong; Liu, Wenlang; Jiang, Xiaohui; Huang, Yangqing; Zong, Leilei; Ding, Haifeng; Shen, Xinyi; Sun, Yujia; Feng, Xiangyang; Li, Xionghao; Song, Yunsong; Gu, Jianing; Wang, Yuhuai; Liu, Hao; Zheng, Zheng","year":2024,"journal":"Scientific reports, 14(1), 16680","doi":"10.1038/s41598-024-66998-8","pmid":"39030216","tags":["GLP-1-receptor-agonists","tirzepatide","GIP","peptide-drug-design"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"BGM0504 achieved a 2-3 fold increase in agonistic activity at both GLP-1R and GIPR compared to tirzepatide, while maintaining equivalent extended plasma half-life, by repositioning the acylation side chain based on molecular dynamics insights.","whyItMatters":"Tirzepatide is already one of the most effective diabetes and obesity drugs available. A peptide that is 2-3x more potent could mean lower doses, fewer side effects, or greater efficacy — potentially advancing the next generation of metabolic disease treatment.","specificNumbers":"BGM0504 was optimized using molecular dynamics to achieve enhanced dual-target agonism at both GLP-1R and GIPR.","methodology":"Molecular dynamics simulations to map peptide-receptor interactions, followed by structure-guided peptide optimization. Validated with in vitro receptor activation assays and in vivo animal studies comparing BGM0504 to tirzepatide.","limitations":"Preclinical data only — no human trials yet. In vitro and animal study results do not always translate to clinical superiority. The 2-3x potency increase in receptor activation may not produce proportionally better clinical outcomes. Safety profile in humans is unknown."},{"rthcId":"RPEP-09619","title":"Colchicine Alleviates Rosacea by Inhibiting Neutrophil Inflammation Activated by the TLR2 Pathway.","authors":"Yuan, Xin; Sheng, Liang; Shi, Guang; Jiang, Leiwei; Lian, Chengxiang","year":2024,"journal":"Inflammation, 47(3), 1002-1014","doi":"10.1007/s10753-023-01956-6","pmid":"38279067","tags":["antimicrobial-peptides-defensins","immune-function","skin-health"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"LL-37 cathelicidin directly binds to TLR2 on neutrophils to drive rosacea inflammation, and colchicine disrupts this binding, reducing inflammatory markers, NET formation, and rosacea-like symptoms in mice.","whyItMatters":"This study reveals the specific molecular mechanism by which the peptide LL-37 causes rosacea — by binding TLR2 on neutrophils. Understanding this peptide-receptor interaction could lead to more targeted treatments for the millions of people living with rosacea.","specificNumbers":"Colchicine reduced redness scores, inflammatory biomarkers, and neutrophil infiltration in the rosacea mouse model.","methodology":"LL-37-induced rosacea mouse model treated with colchicine. Assessed skin redness scores, inflammatory biomarkers via RT-PCR, neutrophil infiltration via immunohistochemistry, NET formation, and TLR2-LL-37 binding via coimmunoprecipitation. Validated with bioinformatics analysis.","limitations":"Mouse rosacea model induced by external LL-37 injection may not fully replicate human disease, where LL-37 overproduction is endogenous. Colchicine has gastrointestinal and other side effects that need clinical evaluation in rosacea patients. No human trial data."},{"rthcId":"RPEP-09620","title":"Lactobacillus reuteri JCM 1112 ameliorates chronic acrylamide-induced glucose metabolism disorder via the bile acid-TGR5-GLP-1 axis and modulates intestinal oxidative stress in mice.","authors":"Yue, Zonghao; Zhao, Feiyue; Guo, Yuqi; Zhang, Yidan; Chen, Yanjuan; He, Le; Li, Lili","year":2024,"journal":"Food & function, 15(12), 6450-6458","doi":"10.1039/d4fo01061b","pmid":"38804210","tags":["GLP-1-receptor-agonists","gut-health"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Three weeks of L. reuteri supplementation restored GLP-1 levels, normalized blood glucose and insulin, reactivated ileal TGR5 and proglucagon expression, and corrected bile acid imbalance in acrylamide-exposed mice.","whyItMatters":"Acrylamide exposure is nearly unavoidable through cooked foods. If it suppresses GLP-1 signaling — a peptide pathway critical for blood sugar control — this could partly explain rising metabolic disease rates. Probiotics that restore GLP-1 function offer a practical dietary intervention.","specificNumbers":"5 mg/kg acrylamide for 10 weeks increased blood glucose and decreased GLP-1; 3 weeks of probiotic or dulaglutide treatment reversed these effects.","methodology":"C57BL/6N mice given oral acrylamide (5 mg/kg body weight) for 10 weeks, then treated for 3 weeks with either dulaglutide (GLP-1 analogue), INT-777 (TGR5 agonist), or Lactobacillus reuteri JCM 1112. Measured blood glucose, serum insulin, GLP-1 levels, bile acid profiles, gene expression (TGR5, proglucagon), and oxidative stress markers.","limitations":"Mouse study with a specific acrylamide dose (5 mg/kg) that may exceed typical human dietary exposure. Results from a single probiotic strain may not apply to other probiotics. Three-week treatment period is short. Human metabolic responses may differ from mice."},{"rthcId":"RPEP-09621","title":"The microbial metabolite agmatine acts as an FXR agonist to promote polycystic ovary syndrome in female mice.","authors":"Yun, Chuyu; Yan, Sen; Liao, Baoying; Ding, Yong; Qi, Xinyu; Zhao, Min; Wang, Kai; Zhuo, Yingying; Nie, Qixing; Ye, Chuan; Xia, Pengyan; Ma, Ming; Li, Rong; Jiang, Changtao; Qiao, Jie; Pang, Yanli","year":2024,"journal":"Nature metabolism, 6(5), 947-962","doi":"10.1038/s42255-024-01041-8","pmid":"38769396","tags":["gut-health","reproductive-health","bioactive-peptides"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"Bacteroides vulgatus-derived agmatine activates FXR to suppress GLP-1 secretion from L cells, causing insulin resistance and ovarian dysfunction. Liraglutide and the arginine decarboxylase inhibitor DFMA both ameliorated PCOS-like symptoms.","whyItMatters":"This connects the gut microbiome to PCOS through a specific GLP-1-suppressing mechanism. It suggests that GLP-1 drugs already on the market (like liraglutide) could potentially treat PCOS, and that targeting gut bacteria or their metabolites could prevent it.","specificNumbers":"PCOS affects 6-20% of women of reproductive age globally. B. vulgatus elevation was previously identified in PCOS patients.","methodology":"Mouse model using B. vulgatus colonization to induce PCOS-like phenotype. Identified agmatine as the causal metabolite via metabolomics. Characterized FXR activation, GLP-1 suppression, insulin resistance, and ovarian dysfunction. Tested liraglutide and DFMA as interventions.","limitations":"Mouse model of PCOS may not fully replicate human disease complexity. Agmatine levels and their role in human PCOS patients need clinical validation. FXR has broad functions beyond GLP-1 regulation, so targeting it could have side effects. B. vulgatus is a common gut bacterium — unclear what triggers its overgrowth in PCOS."},{"rthcId":"RPEP-09622","title":"Cow's Milk Bioactive Molecules in the Regulation of Glucose Homeostasis in Human and Animal Studies.","authors":"Yuzbashian, Emad; Berg, Emily; de Campos Zani, Stepheny C; Chan, Catherine B","year":2024,"journal":"Foods (Basel, Switzerland), 13(17)","doi":"10.3390/foods13172837","pmid":"39272602","tags":["bioactive-peptides","diabetes"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Milk-derived bioactive peptides from whey and casein regulate glucose homeostasis through insulinotropic effects, incretin hormone modulation, and RAAS inhibition, supporting dairy consumption as potentially protective against metabolic disorders.","whyItMatters":"Dairy is consumed by billions of people daily. Understanding how milk peptides affect insulin and blood sugar at a mechanistic level could inform dietary recommendations for diabetes prevention and lead to development of dairy-derived functional foods or peptide supplements.","specificNumbers":"Review covers multiple classes of milk bioactive molecules across human and animal studies.","methodology":"Narrative review synthesizing evidence from human clinical studies, rodent experiments, and in vitro mechanistic studies on cow's milk bioactive molecules and glucose metabolism.","limitations":"Narrative review, not a systematic review or meta-analysis. Milk composition varies significantly by cow breed, diet, and processing methods. Whole milk effects may differ from isolated peptide effects. Individual lactose tolerance and gut microbiome composition affect responses. Many proposed mechanisms are based on in vitro or animal data."},{"rthcId":"RPEP-09623","title":"Application of Cell Penetrating Peptides for Intracellular Delivery of Endostatin: A Computational Approach.","authors":"Zamani, Mozhdeh; Nezafat, Navid; Mokarram, Pooneh; Kadkhodaei, Behnam","year":2024,"journal":"Current computer-aided drug design, 20(3), 208-223","doi":"10.2174/1573409919666230426093230","pmid":"37170980","tags":["peptide-drug-delivery","cancer-research"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Four CPPs (Cyt c-ss-MAP, TP-biot1, MPGα, DPV1047) were computationally predicted to form stable, non-antigenic fusions with endostatin that could improve its delivery and overcome its clinical limitations of poor stability and low half-life.","whyItMatters":"Endostatin showed promise in early cancer research but failed clinically due to instability. If cell-penetrating peptides can solve this delivery problem, it could revive endostatin as an anti-cancer therapy and demonstrate a broader approach for rescuing unstable protein drugs.","specificNumbers":"Multiple CPP candidates were computationally evaluated for endostatin binding and delivery characteristics.","methodology":"Computational study using multiple bioinformatics tools: ProtParam for stability/hydrophobicity, VaxiJen for antigenicity prediction, DeepLoc-1.0 for subcellular localization, I-TASSER for 3D structure modeling, and PROCHECK/ERRAT/Verify3D/ProSA-Web for model validation.","limitations":"Entirely computational — no experimental validation in cells, animals, or humans. Computational predictions do not always match real-world behavior. CPP-fusion proteins may have unexpected toxicity, immunogenicity, or stability issues in biological systems. The transition from in silico to in vivo often reveals unforeseen challenges."},{"rthcId":"RPEP-09624","title":"Effectiveness and safety of monthly versus quarterly fremanezumab for migraine prevention: An Italian, multicenter, real-life study.","authors":"Zanandrea, Laura; Messina, Roberta; Cetta, Ilaria; Genovese, Federica; Guerrieri, Simone; Vernieri, Fabrizio; Altamura, Claudia; Cevoli, Sabina; Favoni, Valentina; Colombo, Bruno; Filippi, Massimo","year":2024,"journal":"European journal of neurology, 31(12), e16410","doi":"10.1111/ene.16410","pmid":"39233446","tags":["CGRP-peptides","neurological-conditions"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Both monthly (225 mg) and quarterly (675 mg) fremanezumab significantly reduced migraine days, headache days, and disability scores, with equivalent outcomes at 6 months despite a slight monthly advantage in the first quarter.","whyItMatters":"Choosing between monthly and quarterly injections affects patient convenience and adherence. Real-world evidence that quarterly dosing matches monthly dosing by 6 months gives migraine patients a less burdensome option without sacrificing effectiveness.","specificNumbers":"95 patients enrolled across Italian centers; 225 mg monthly vs. 675 mg quarterly over 3 months of treatment.","methodology":"Prospective, multicenter, real-life Italian study. 95 migraine patients (49 monthly, 46 quarterly) assessed at baseline, 3 months, and 6 months. Measured monthly migraine days, headache days, acute medication use, HIT-6, MIDAS, and NRS scores. 79 patients completed 6-month follow-up.","limitations":"Non-randomized design — patients chose or were assigned regimens based on clinical judgment, so groups may differ. Moderate sample size (95 patients). Single-country study from Italian centers. Only 6 months of follow-up. No blinding or placebo control."},{"rthcId":"RPEP-09625","title":"The effect of SP/NK1R on expression and activity of glutaredoxin and thioredoxin proteins in prostate cancer cells.","authors":"Zarei Shandiz, Sara; Assaran Darban, Reza; Javid, Hossein; Ghahremanloo, Atefeh; Hashemy, Seyed Isaac","year":2024,"journal":"Naunyn-Schmiedeberg's archives of pharmacology, 397(8), 5875-5882","doi":"10.1007/s00210-024-02996-x","pmid":"38334824","tags":["substance-P","neuropeptides","cancer-research"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Substance P/NK1R signaling increased ROS and decreased both the expression and activity of glutaredoxin and thioredoxin in PC3 and LNCaP prostate cancer cells. Aprepitant (NK1R antagonist) reversed all of these effects.","whyItMatters":"Substance P is elevated in many cancers. Understanding how this neuropeptide disrupts cellular antioxidant defenses reveals a new mechanism of cancer promotion and identifies NK1R blockade as a potential therapeutic strategy for prostate cancer.","specificNumbers":"The study measured changes in both expression and activity levels of glutaredoxin and thioredoxin proteins in response to SP/NK1R activation.","methodology":"In vitro study using PC3 and LNCaP prostate cancer cell lines. Cells treated with Substance P and/or aprepitant (NK1R antagonist). Measured cell viability (resazurin assay), intracellular ROS levels, and glutaredoxin/thioredoxin expression (qRT-PCR) and activity (commercial kits).","limitations":"In vitro study using established cancer cell lines, which do not replicate the complexity of tumors in the body. Aprepitant concentrations used in cell culture may not match achievable clinical doses. No animal or human data. The specific contribution of this redox mechanism to overall cancer progression is unclear."},{"rthcId":"RPEP-09626","title":"Incretin-based therapy: a new horizon in diabetes management.","authors":"Zarei, Malek; Sahebi Vaighan, Navideh; Farjoo, Mohammad Hadi; Talebi, Soosan; Zarei, Mohammad","year":2024,"journal":"Journal of diabetes and metabolic disorders, 23(2), 1665-1686","doi":"10.1007/s40200-024-01479-3","pmid":"39610543","tags":["GLP-1-receptor-agonists","GIP","diabetes"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Incretin-based therapies protect against diabetic complications across multiple organ systems: neuropathy, nephropathy, retinopathy, and cardiovascular disease, beyond their glucose-lowering effects.","whyItMatters":"Diabetic complications — nerve damage, kidney failure, blindness, and heart disease — cause more suffering than high blood sugar itself. Understanding that incretin peptide drugs protect multiple organ systems positions them as foundational diabetes therapies, not just blood sugar medications.","specificNumbers":"Review covers the role of incretins across multiple organ systems affected by diabetes.","methodology":"Comprehensive narrative review of published literature on incretin biology, GLP-1 receptor agonists, DPP-4 inhibitors, and next-generation multi-receptor agonists in diabetes management and complication prevention.","limitations":"Narrative review without systematic methodology or meta-analysis. Some organ-protective effects are based on preclinical or short-term clinical data. Long-term safety data for newer multi-receptor agonists is limited. Individual patient responses to incretin therapies vary."},{"rthcId":"RPEP-09627","title":"Effect of hydroxyethyl starch on drug stability and release of semaglutide in PLGA microspheres.","authors":"Zeng, Han; Song, Jiaxin; Li, Yiyao; Guo, Chen; Zhang, Yu; Yin, Tian; He, Haibing; Gou, Jingxin; Tang, Xing","year":2024,"journal":"International journal of pharmaceutics, 654, 123991","doi":"10.1016/j.ijpharm.2024.123991","pmid":"38471578","tags":["semaglutide","peptide-drug-delivery","GLP-1-receptor-agonists"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"HES-containing PLGA microspheres achieved 94.38% semaglutide encapsulation, 83.23% controlled release over 44 days, prevented 30.65% drug loss versus HES-free microspheres, and provided ~3 weeks of glycemic control in vivo.","whyItMatters":"Weekly semaglutide injections are a barrier to patient adherence. A monthly injectable microsphere formulation would significantly reduce injection burden, potentially improving outcomes for millions of diabetes and obesity patients.","specificNumbers":"HES addition to the W1 phase showed significant enhancement of semaglutide stability compared to formulations without the starch protectant.","methodology":"Formulation study using W1/O/W2 double emulsion method to create PLGA microspheres. Tested hydroxyethyl starch addition at various concentrations. Characterized encapsulation efficiency, in vitro release kinetics, semaglutide structural integrity, and in vivo glycemic control.","limitations":"Primarily in vitro formulation work with limited in vivo data. Human pharmacokinetics, bioavailability, and injection-site tolerability are unknown. Scale-up manufacturing challenges for microspheres are not addressed. The ~3 weeks of glycemic control observed in animals may not translate directly to humans."},{"rthcId":"RPEP-09628","title":"An open-label 16-week study of liraglutide in adolescents with obesity post-sleeve gastrectomy.","authors":"Zenno, Anna; Nwosu, Ejike E; Fatima, Syeda Z; Nadler, Evan P; Mirza, Nazrat M; Brady, Sheila M; Turner, Sara A; Yang, Shanna B; Lazareva, Julia; Te-Vasquez, Jennifer A; Chen, Kong Y; Chung, Stephanie T; Yanovski, Jack A","year":2024,"journal":"Pediatric obesity, 19(11), e13154","doi":"10.1111/ijpo.13154","pmid":"39103247","tags":["GLP-1-receptor-agonists","liraglutide","weight-management"],"studyType":"RCT","evidenceStrength":"preliminary","keyFinding":"Liraglutide produced a 4.3% BMI reduction (p<0.001) in 34 adolescents with persistent obesity after sleeve gastrectomy, with significant improvements in fasting glucose and HbA1c and 91% study completion.","whyItMatters":"Teenagers who regain weight after bariatric surgery face serious long-term health risks with very few treatment options. Demonstrating that GLP-1 drugs work in this population opens a new treatment pathway for a vulnerable group with limited alternatives.","specificNumbers":"Adolescents aged 12-20.99 years, at least 1 year post-sleeve gastrectomy, received liraglutide starting at 0.6 mg for 16 weeks.","methodology":"Open-label, 16-week pilot study. Enrolled adolescents aged 12-21 with obesity at least 1 year after sleeve gastrectomy. Liraglutide titrated from 0.6 mg/day to max 3 mg/day. Assessed BMI, fasting labs, and oral glucose tolerance at baseline and end-treatment.","limitations":"Open-label design with no control group — weight loss could be partly due to study participation effects. Small sample of 34 teens. Only 16 weeks of follow-up — long-term effects unknown. Teens with poor initial surgical response also responded less to liraglutide, suggesting some patients may remain difficult to treat."},{"rthcId":"RPEP-09629","title":"De Novo Antimicrobial Peptide Design with Feedback Generative Adversarial Networks.","authors":"Zervou, Michaela Areti; Doutsi, Effrosyni; Pantazis, Yannis; Tsakalides, Panagiotis","year":2024,"journal":"International journal of molecular sciences, 25(10)","doi":"10.3390/ijms25105506","pmid":"38791544","tags":["antimicrobial-peptides","AI-drug-design","machine-learning"],"studyType":"computational","evidenceStrength":"preliminary","keyFinding":"Researchers improved an AI system called FBGAN (Feedback Generative Adversarial Network) for designing new antimicrobial peptides by upgrading its classifier components. They introduced two enhanced classifiers: one using k-mers (short sequence fragments) and another using transfer learning from ESM2, a large protein language model.\n\nBoth improved classifiers boosted FBGAN's ability to generate promising antimicrobial peptide candidates, achieving performance comparable to or better than established AI methods like AMPGAN and HydrAMP. The key insight is that better 'judgment' (classification accuracy) in the AI system directly improves the quality of peptides it generates.","whyItMatters":"As antibiotic resistance grows, AI-driven design of antimicrobial peptides could dramatically accelerate the development of new antibiotics. This study shows that combining generative AI with better classifiers — including protein language models trained on evolutionary data — improves the pipeline for creating novel AMP candidates. It demonstrates how techniques from large language models can be applied to drug discovery.","specificNumbers":"2 improved classifiers · Performance surpasses original FBGAN · Comparable or superior to AMPGAN + HydrAMP · Leverages ESM2 protein language model","methodology":"Computational study enhancing the FBGAN framework with two alternative classifiers. The first used k-mers analysis, the second applied transfer learning from ESM2 (Evolutionary Scale Modeling 2). Generated peptides were evaluated computationally against established methods (AMPGAN, HydrAMP) for antimicrobial peptide design quality. No experimental wet-lab validation was performed.","limitations":"Entirely computational — no lab testing of generated peptides. Predicted antimicrobial activity may not match real-world performance. Comparison is against other computational methods, not actual biological activity data. The generated peptides would need synthesis and testing against real bacteria to confirm their antimicrobial properties."},{"rthcId":"RPEP-09630","title":"Revealing the dynamic mechanism of cell-penetrating peptides across cell membranes at the single-molecule level.","authors":"Zhai, Yuhang; Li, Siying; Wang, Hui; Shan, Yuping","year":2024,"journal":"Journal of materials chemistry. B, 12(23), 5589-5593","doi":"10.1039/d4tb00522h","pmid":"38741568","tags":["peptide-drug-delivery","peptide-drug-design"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Cationic CPPs (TAT, MAP) show stronger membrane interaction via electrostatic forces, while hydrophobic Pep-7 crosses membranes faster and shows selective penetration of cancer cells over normal cells.","whyItMatters":"Designing peptide-based drug delivery has been largely trial-and-error. By revealing exactly how different CPP types interact with and cross cell membranes at the single-molecule level, this research provides a rational framework for engineering more effective and selective peptide delivery systems.","specificNumbers":"Individual CPP molecules were tracked at the single-molecule level during membrane interaction and translocation.","methodology":"Single-molecule force spectroscopy (SMFS) and force tracing technique based on atomic force microscopy (AFM). Dynamic force spectroscopy (DFS) analysis used to quantify interaction forces and trans-membrane kinetics for three CPPs (TAT48-60, MAP, Pep-7) on cancer and normal cell lines.","limitations":"Highly controlled in vitro conditions using AFM do not replicate the complexity of living tissues. Only three CPPs were compared. Cancer vs. normal cell selectivity was tested with only one normal cell line (Vero). Real-world drug delivery involves many additional factors beyond membrane crossing."},{"rthcId":"RPEP-09631","title":"Recent Advances in Targeted Cancer Therapy: Are PDCs the Next Generation of ADCs?","authors":"Zhang, Baochen; Wang, Mo; Sun, Li; Liu, Jiawei; Yin, Libinghan; Xia, Mingjing; Zhang, Ling; Liu, Xifu; Cheng, Yu","year":2024,"journal":"Journal of medicinal chemistry, 67(14), 11469-11487","doi":"10.1021/acs.jmedchem.4c00106","pmid":"38980167","tags":["peptide-drug-design","cancer-research","peptide-drug-delivery"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"PDCs offer advantages over ADCs including smaller molecular size for better tumor penetration, lower immunogenicity, more cost-effective production, and greater chemical flexibility for design optimization.","whyItMatters":"ADCs represent a multi-billion dollar cancer drug class, but their limitations leave room for improvement. PDCs could democratize targeted cancer therapy by being cheaper to produce, easier to modify, and better at reaching solid tumors — potentially expanding access to precision oncology.","specificNumbers":"Review published in a top medicinal chemistry journal covering the evolution from ADCs to PDCs across multiple cancer types.","methodology":"Perspective review published in the Journal of Medicinal Chemistry summarizing current ADC and PDC research, analyzing structural innovations in conjugate design, and identifying challenges for PDC development.","limitations":"Most PDCs are in preclinical or early clinical stages — far less validated than the established ADC field. Peptide stability and short half-life remain significant challenges. The review does not include head-to-head clinical comparisons between ADCs and PDCs. Theoretical advantages may not fully translate to clinical superiority."},{"rthcId":"RPEP-09632","title":"Efficacy and Safety of Mazdutide in Chinese Patients With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial.","authors":"Zhang, Bo; Cheng, Zhifeng; Chen, Ji; Zhang, Xin; Liu, Dexue; Jiang, Hongwei; Ma, Guoqing; Wang, Xiaoyun; Gan, Shenglian; Sun, Juan; Jin, Ping; Yi, Jianjun; Shi, Bimin; Ma, Jianhua; Ye, Shandong; Wang, Guixia; Ji, Linong; Gu, Xuejiang; Yu, Ting; An, Pei; Deng, Huan; Li, Haoyu; Li, Li; Ma, Qingyang; Qian, Lei; Yang, Wenying","year":2024,"journal":"Diabetes care, 47(1), 160-168","doi":"10.2337/dc23-1287","pmid":"37943529","tags":["GLP-1-receptor-agonists","glucagon","diabetes","weight-management"],"studyType":"RCT","evidenceStrength":"strong","keyFinding":"Mazdutide 6 mg reduced HbA1c by 1.67% and body weight by 7.1% over 20 weeks, significantly exceeding both placebo and the reference GLP-1 drug dulaglutide on weight loss endpoints.","whyItMatters":"While tirzepatide targets GLP-1/GIP, mazdutide targets GLP-1/glucagon — a different dual-agonist approach. Glucagon co-activation may enhance fat burning and liver fat reduction beyond what GLP-1 alone achieves, potentially offering unique metabolic benefits.","specificNumbers":"203 patients randomized: 51 to 3 mg, 49 to 4.5 mg, 53 to 6 mg mazdutide, and 50 to placebo. HbA1c range at entry: 7.0-10.5%.","methodology":"Randomized, double-blind, placebo-controlled phase 2 trial. 250 Chinese adults with T2D (HbA1c 7.0-10.5%) randomized to mazdutide 3 mg (n=51), 4.5 mg (n=49), 6 mg (n=49), open-label dulaglutide 1.5 mg (n=50), or placebo (n=51) for 20 weeks. Primary endpoint: HbA1c change at week 20.","limitations":"Phase 2 trial with moderate sample size and 20-week duration. Studied only in Chinese patients — efficacy in other populations needs confirmation. Open-label dulaglutide arm introduces potential bias. GI side effects were common (36% diarrhea). Long-term safety of glucagon co-activation unknown."},{"rthcId":"RPEP-09633","title":"PepT1-targeted nanodrug based on co-assembly of anti-inflammatory peptide and immunosuppressant for combined treatment of acute and chronic DSS-induced ColitiS.","authors":"Zhang, Daifang; Jiang, Longqi; Yu, Fengxu; Yan, Pijun; Liu, Yong; Wu, Ya; Yang, Xi","year":2024,"journal":"Frontiers in pharmacology, 15, 1442876","doi":"10.3389/fphar.2024.1442876","pmid":"39211778","tags":["bioactive-peptides","peptide-drug-delivery","gut-health"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"KPV-FK506 co-assembled nanoparticles targeted PepT1 on inflamed gut epithelium and outperformed either component alone in reducing inflammation, immune cell infiltration, and restoring tight junction proteins in both acute and chronic colitis models.","whyItMatters":"IBD affects millions worldwide with limited treatment options. A peptide-based nanodrug that targets inflamed tissue directly could deliver more effective treatment with fewer systemic side effects than current oral or IV immunosuppressants.","specificNumbers":"The nanodrug targeted PepT1 transporters and treated both acute and chronic DSS-induced colitis models in mice.","methodology":"Mouse study using DSS-induced acute (2.5% DSS) and chronic (4% DSS) colitis models. Compared nanoparticles (NPs), KPV peptide alone, FK506 alone, DSS control, and saline control. Assessed body weight, colon length, disease activity, inflammatory cytokines, oxidative stress markers, immune cell infiltration, and tight junction protein expression.","limitations":"Mouse colitis model does not perfectly replicate human IBD. PepT1 expression patterns may differ in humans. Long-term safety, stability, and scalability of carrier-free nanoparticles are unknown. No comparison with current standard-of-care IBD treatments like biologics."},{"rthcId":"RPEP-09634","title":"The current landscape of the antimicrobial peptide melittin and its therapeutic potential.","authors":"Zhang, Hai-Qian; Sun, Chengbiao; Xu, Na; Liu, Wensen","year":2024,"journal":"Frontiers in immunology, 15, 1326033","doi":"10.3389/fimmu.2024.1326033","pmid":"38318188","tags":[],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Melittin, the main active peptide in bee venom, has demonstrated antitumor, antiviral, and anti-inflammatory effects in both lab and animal studies. It can enhance the effectiveness of existing first-line drugs and may be particularly valuable for diseases without established treatments.\n\nHowever, melittin's mechanism of action — punching holes in cell membranes using its positively charged amino acids — also causes significant toxicity to healthy cells, including hemolysis (destruction of red blood cells). Modern engineering strategies including nanoparticle modification, antibody conjugation, structural modifications, and gene technology have been shown to improve melittin's selectivity for target cells while reducing its toxic effects on normal tissue.","whyItMatters":"Antimicrobial resistance and treatment-resistant cancers are among the biggest challenges in medicine. Melittin's ability to kill cells by disrupting membranes — a mechanism that's difficult for bacteria and cancer cells to develop resistance against — makes it a valuable scaffold for drug development. The key challenge has been taming its toxicity, and this review shows that multiple modification strategies are making clinical use increasingly feasible.","specificNumbers":"Main component of bee venom · cationic amphiphilic peptide · linear α-helix structure · antitumor + antiviral + anti-inflammatory effects · 4 modification strategies reviewed","methodology":"This is a comprehensive narrative review summarizing published research on melittin's pharmacological properties (antiviral, antitumor, anti-inflammatory), its mechanisms of action, its toxicity challenges, and the engineering strategies being developed to overcome those challenges for potential clinical use.","limitations":"As a review, this paper synthesizes existing literature rather than presenting new data. Most evidence for melittin's therapeutic effects comes from in vitro and animal studies. The modification strategies discussed are largely at the preclinical stage, with limited clinical trial data available."},{"rthcId":"RPEP-09635","title":"Semaglutide for the prevention of atrial fibrillation: A systematic review and meta-analysis.","authors":"Zhang, Hong-Da; Ding, Lei; Liu, Ke; Mi, Li-Jie; Zhang, Ai-Kai; Yu, Feng-Yuan; Yan, Xin-Xin; Peng, Fu-Hua; Shen, Yu-Jing; Tang, Min","year":2024,"journal":"Diabetes & metabolic syndrome, 18(6), 103067","doi":"10.1016/j.dsx.2024.103067","pmid":"38955095","tags":["semaglutide","GLP-1-receptor-agonists","cardiovascular-health"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Semaglutide reduced atrial fibrillation occurrence by 30% overall (RR 0.70, 95% CI 0.52-0.95), with subgroup benefits of 51% reduction with oral semaglutide and 29% in T2DM patients.","whyItMatters":"Atrial fibrillation increases stroke risk five-fold and affects millions worldwide. If semaglutide prevents AFib in addition to its diabetes and weight benefits, this represents a major additional cardiovascular protection for the millions already taking it.","specificNumbers":"Meta-analysis pooled randomized controlled trials through December 2023 examining AF incidence in semaglutide versus control groups.","methodology":"Systematic review and meta-analysis of 21 randomized controlled trials (25,957 patients) from MEDLINE, EMBASE, Cochrane CENTRAL, and clinicaltrials.gov through December 2023. Calculated relative risks with 95% CIs for overall population and subgroups.","limitations":"AFib was a secondary or safety endpoint in the included trials, not the primary focus. The benefit did not reach significance vs placebo alone (RR 0.77, CI 0.56-1.07) or in obesity-only patients. Different trial designs, populations, and follow-up durations were pooled. A dedicated AFib prevention trial would provide stronger evidence."},{"rthcId":"RPEP-09636","title":"Benchmarking the medication efficiency and technological progress of diabetes drugs.","authors":"Zhang, Hongwei; Wang, Chen; Xu, Ting; Liu, Lin; Ban, Xuyan; Liu, Weijie; Yan, Chenli; Han, Xiaodong","year":2024,"journal":"Frontiers in public health, 12, 1396832","doi":"10.3389/fpubh.2024.1396832","pmid":"39583077","tags":["GLP-1-receptor-agonists","diabetes"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Oral semaglutide, subcutaneous semaglutide, and dulaglutide achieved the highest medication efficiency scores among 20 T2D drugs, while lixisenatide and liraglutide scored lower despite being in the same GLP-1 class.","whyItMatters":"With 20+ diabetes drug options, understanding which ones deliver the most benefit per dose helps both patients and clinicians make better treatment decisions. The dominance of GLP-1 peptides confirms their position as the most effective modern diabetes drug class.","specificNumbers":"Analysis covers tens of FDA-approved diabetes drugs from the 1950s through present day.","methodology":"Data envelopment analysis (DEA) model using FDA data and meta-analysis results. Evaluated 20 T2D drugs on benefits (glucose lowering, weight loss) and harms (mortality) relative to dosing frequency. Used directional distance function to handle multidimensional outcomes.","limitations":"DEA efficiency models involve methodological choices about input/output weighting. Newer drugs have less long-term safety data. Analysis does not account for cost, which is a major real-world treatment factor. Some drugs serve different clinical niches that simple efficiency rankings may not capture."},{"rthcId":"RPEP-09637","title":"Multibarrier-penetrating drug delivery systems for deep tumor therapy based on synergistic penetration strategy.","authors":"Zhang, Hui-Feng; Yu, Huan; Pan, Shuang-Xue; Zhang, Chuang; Ma, Ying-Hui; Zhang, Yan-Fei; Zuo, Li-Li; Hao, Cheng-Yi; Lin, Xiao-Ying; Geng, Hao; Wu, Di; Mu, Shang-Qiang; Yu, Wei-Lun; Shi, Nian-Qiu","year":2024,"journal":"Biomaterials science, 12(9), 2321-2330","doi":"10.1039/d3bm01959d","pmid":"38488841","tags":["peptide-drug-delivery","cancer-research"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Liposomes coated with both tumor-penetrating (cyclic iNGR) and cell-penetrating (R9) peptides achieved synergistic penetration of multiple biological barriers, delivering doxorubicin deep into tumor tissue and cells in vitro and in vivo.","whyItMatters":"Many cancer drugs are effective at killing cancer cells in a dish but fail in patients because they cannot penetrate solid tumors deeply enough. This dual-peptide approach solves multiple penetration barriers simultaneously, potentially making existing drugs more effective.","specificNumbers":"The modified NGR peptide demonstrated enhanced multi-barrier penetration compared to the original iNGR tumor-penetrating peptide.","methodology":"Developed Lip-mbPDS liposomes coated with R9 CPP and cyclic iNGR peptide. Tested in CD13-positive HT1080 fibrosarcoma cells using confocal microscopy, cell internalization/toxicity assays, 3D tumor spheroid penetration, and in vivo antitumor efficacy in mouse models.","limitations":"Preclinical study using a single tumor model (HT1080 fibrosarcoma). Different tumor types may present different penetration challenges. Liposome stability and manufacturing scalability not addressed. Clinical translation requires extensive safety and efficacy testing in humans."},{"rthcId":"RPEP-09638","title":"GLP-1 receptor agonist-induced diabetic ketoacidosis: A case report.","authors":"Zhang, Jiaming; Ma, Ying; Zu, Qianhe; Wang, Xiaohui; Zhang, Yao","year":2024,"journal":"Medicine, 103(39), e39799","doi":"10.1097/MD.0000000000039799","pmid":"39331877","tags":["GLP-1-receptor-agonists","diabetes"],"studyType":"case series","evidenceStrength":"preliminary","keyFinding":"A patient misdiagnosed as type 2 diabetes developed severe DKA within 24 hours of starting dulaglutide and discontinuing insulin, leading to her correct diagnosis of LADA.","whyItMatters":"As GLP-1 drugs are prescribed to millions for diabetes and weight loss, cases like this highlight the importance of correctly identifying diabetes type before prescribing. LADA is frequently misdiagnosed as type 2 diabetes, and GLP-1 drugs cannot replace insulin in autoimmune diabetes.","specificNumbers":"One documented case of DKA in a T2D patient on dulaglutide — rare but clinically significant.","methodology":"Single case report documenting clinical presentation, diagnostic workup, emergency treatment, and outcome of GLP-1 agonist-induced DKA in a patient subsequently diagnosed with LADA.","limitations":"Single case report — the weakest form of clinical evidence. The patient had multiple risk factors (12-year disease duration, insulin discontinuation, potential LADA). DKA could have been triggered primarily by stopping insulin rather than by dulaglutide itself. Cannot generalize to all GLP-1 drug users."},{"rthcId":"RPEP-09639","title":"Circulating neuropeptide Y as a biomarker in postoperative atrial fibrillation cases administered off-pump coronary bypass Graft surgery.","authors":"Zhang, Jian; He, Yuanchen; Yin, Zongtao; Li, Rui; Zhang, Xiaohui; Wang, Yang; Wang, Huishan","year":2024,"journal":"Heliyon, 10(10), e31251","doi":"10.1016/j.heliyon.2024.e31251","pmid":"38803941","tags":["neuropeptide-Y","cardiovascular-health"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Pre-surgical plasma NPY levels independently predicted POAF (OR 1.055 per unit increase, P=0.041) alongside age (OR 1.135) and left atrial size (OR 1.136) in multivariable analysis. NPY was significantly higher in the POAF group (31.72 vs 27.95, P=0.014).","whyItMatters":"A simple blood test measuring NPY levels before heart surgery could identify patients at high risk for postoperative atrial fibrillation, enabling preventive interventions that reduce complications, hospital stays, and stroke risk.","specificNumbers":"Patients were enrolled from January 1 to May 31, 2020, undergoing isolated off-pump CABG with NPY measurements.","methodology":"Prospective cohort study of 120 consecutive patients undergoing isolated off-pump CABG (January-May 2020). Pre-operative plasma NPY measured by ELISA. POAF detected by 7-day Holter monitoring. Multivariable logistic regression for independent predictors.","limitations":"Single-center study with 120 patients during a 5-month period. The modest odds ratio for NPY (1.055) suggests it adds incremental value but is not a strong standalone predictor. Association does not prove causation. Heart rate variability correlations were weak-to-moderate. External validation in larger cohorts needed."},{"rthcId":"RPEP-09640","title":"Comparative analysis of semaglutide induced adverse reactions: Insights from FAERS database and social media reviews with a focus on oral vs subcutaneous administration.","authors":"Zhang, Jing; Wang, Xiaofen; Zhou, Yiting","year":2024,"journal":"Frontiers in pharmacology, 15, 1471615","doi":"10.3389/fphar.2024.1471615","pmid":"39502525","tags":["semaglutide","GLP-1-receptor-agonists"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"GI disorders accounted for 30.19% of oral and 27.76% of subcutaneous semaglutide adverse events. Novel signals included pancreatic failure (ROR 36.34) for injectable and Dupuytren's contracture (ROR 46.85) for oral semaglutide.","whyItMatters":"With millions of patients choosing between oral and injectable semaglutide, understanding the different side effect profiles helps inform that choice. Identifying new safety signals in such a widely used drug is critical for patient safety monitoring.","specificNumbers":"Analysis covered FAERS database reports and social media data comparing oral and subcutaneous semaglutide adverse event patterns.","methodology":"Pharmacovigilance analysis of 19,289 semaglutide adverse events from FDA FAERS database (Q1 2018-Q2 2023) and 422 patient reviews from WebMD and AskaPatient. Calculated reporting odds ratios (ROR) to identify disproportionate safety signals. Compared oral vs subcutaneous formulations.","limitations":"FAERS data is based on voluntary reporting, which introduces significant biases — adverse events are underreported and reporting rates vary by severity and publicity. Social media data is unverified. ROR signals indicate disproportionate reporting, not causation or incidence rates. Novel signals (pancreatic failure, Dupuytren's) need confirmation in controlled studies."},{"rthcId":"RPEP-09641","title":"Bombesin protects myocardium against ischemia/reperfusion injury via activation of the Keap1-Nrf2-HO-1 signaling pathway.","authors":"Zhang, Jinyi; Du, Yanhuan; Xiong, Zhenyu; Cheng, Hang; Du, Yi; Xiong, Yulian; Lv, Jianfeng; Huang, Wenquan; Qiu, Kuncheng; Zhang, Shizhong","year":2024,"journal":"Peptides, 180, 171279","doi":"10.1016/j.peptides.2024.171279","pmid":"39053647","tags":["bioactive-peptides","cardiovascular-health"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Bombesin improved cardiac function, reduced infarct size, attenuated oxidative stress (increased SOD, GSH; decreased MDA), and reduced apoptosis through Keap1-Nrf2-HO-1 pathway activation. All protective effects were blocked by a bombesin receptor antagonist.","whyItMatters":"Reperfusion injury is a major problem in cardiac medicine — it worsens damage even after successful treatment of a heart attack. Discovering that a natural gut peptide activates the heart's antioxidant defenses could lead to new protective strategies during cardiac procedures.","specificNumbers":"Bombesin activated the Keap1-Nrf2-HO-1 pathway and reduced MIRI in both isolated heart and whole-animal models.","methodology":"Two rat IRI models: ex vivo Langendorff perfused hearts (30 min global ischemia + 120 min reperfusion) and in vivo coronary artery ligation (30 min + 120 min reperfusion) in Sprague-Dawley rats. Measured infarct size, LV function, oxidative stress markers, apoptosis (TUNEL), and Keap1/Nrf2/HO-1 expression.","limitations":"Animal study in rats — human cardiac physiology and bombesin responses may differ. Clinical administration of bombesin during a heart attack would require rapid delivery and precise timing. Safety profile of exogenous bombesin in cardiac patients is completely unknown. Single study with no replication reported."},{"rthcId":"RPEP-09642","title":"Time-Efficacy Relationship of Semaglutide in the Treatment of Type 2 Diabetes Mellitus: A Model-Based Meta-Analysis.","authors":"Zhang, Ke; Zhao, Aiping; Wang, Zhen; Ye, Kaihe; Xu, Zhaosi; Gong, Xiao; Zhu, Guanghu","year":2024,"journal":"Clinical pharmacokinetics, 63(12), 1679-1688","doi":"10.1007/s40262-024-01449-1","pmid":"39549228","tags":["semaglutide","GLP-1-receptor-agonists","diabetes"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Semaglutide 0.5 mg achieved Emax of -1.58% HbA1c reduction and 1 mg achieved -1.87%, with a rebound rate of 0.018 after peak efficacy. Baseline HbA1c predicted time to 50% effect, and male proportion influenced maximum efficacy.","whyItMatters":"Understanding the time-course of semaglutide's effects helps patients and clinicians set realistic expectations — knowing when peak benefit occurs and that a slight rebound is normal, not a treatment failure.","specificNumbers":"Modified Emax model with rebound effects built from multiple trial datasets; baseline HbA1c identified as the strongest covariate.","methodology":"Model-based meta-analysis using data from PubMed, Embase, Cochrane, and Web of Science databases. Built a modified maximum effect (Emax) model with rebound component. Simulated dose-response for 0-2 mg doses. Assessed model fit using goodness-of-fit plots and visual prediction checking.","limitations":"Models simplify complex individual biological responses. The rebound effect may reflect natural disease progression rather than drug tolerance. Model based on published aggregate data, not individual patient data. Does not account for weight-related or cardiovascular endpoints."},{"rthcId":"RPEP-09643","title":"KPV and RAPA Self-Assembled into Carrier-Free Nanodrugs for Vascular Calcification Therapy.","authors":"Zhang, Li; Li, Dongze; Aierken, Yierpani; Zhang, Jie; Liu, Zhenyu; Lin, Zipeng; Jiang, Longqi; Li, Qingzhu; Wu, Ya; Liu, Yong","year":2024,"journal":"Advanced healthcare materials, 13(32), e2402320","doi":"10.1002/adhm.202402320","pmid":"39252648","tags":["bioactive-peptides","cardiovascular-health","peptide-drug-delivery"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Self-assembled KPV-RAPA carrier-free nanoparticles significantly inhibited vascular calcification in vitro and in vivo by simultaneously suppressing inflammation and activating autophagy, outperforming individual treatments.","whyItMatters":"Vascular calcification affects millions and has no approved drug therapy. By targeting two key disease mechanisms — inflammation and impaired autophagy — in a simple, safe nanoformulation, this peptide-drug combination addresses a critical unmet need in cardiovascular medicine.","specificNumbers":"KPV and RAPA self-assembled without carriers, overcoming the low drug loading and complex preparation issues of traditional nanomedicines.","methodology":"Co-assembly of KPV peptide and rapamycin into carrier-free nanoparticles. Characterized stability and safety. Tested in both in vitro calcification models and in vivo mouse models of vascular calcification. Assessed inflammatory markers and autophagy activation.","limitations":"Preclinical study in mouse models that may not fully replicate human vascular calcification. Long-term safety unknown. Clinical translation requires extensive testing. Vascular calcification in humans involves complex pathways beyond inflammation and autophagy."},{"rthcId":"RPEP-09644","title":"Efficacy and Safety of Oral Semaglutide in the Treatment of Type 2 Diabetes: A Meta-Analysis.","authors":"Zhang, Lin; Hua, Zixin; Fang, Zhenwei; Wei, Juanjuan; Lin, Yang","year":2024,"journal":"Journal of clinical pharmacology, 64(10), 1312-1325","doi":"10.1002/jcph.2483","pmid":"38874130","tags":["semaglutide","GLP-1-receptor-agonists","diabetes"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Oral semaglutide 14 mg reduced HbA1c by 1.08% vs placebo and 0.37% vs active comparators, with dose-dependent efficacy. It outperformed empagliflozin, sitagliptin, liraglutide, and dulaglutide on blood sugar and weight endpoints.","whyItMatters":"Many diabetes patients resist injectable drugs. Oral semaglutide removes the needle barrier while matching or exceeding the performance of other leading diabetes medications. This meta-analysis provides comprehensive evidence supporting its clinical value.","specificNumbers":"Meta-analysis of randomized controlled trials through February 2023 examining oral semaglutide versus comparators.","methodology":"Systematic review and meta-analysis of 10 RCTs (9,541 patients) from PubMed, Embase, Cochrane Library, Web of Science, and Chinese-language databases through February 2023. Compared oral semaglutide 3/7/14 mg versus placebo and active comparators (empagliflozin, sitagliptin, liraglutide, dulaglutide).","limitations":"Included trials had varying durations, populations, and background therapies. The 3 mg dose showed less consistent benefits. GI side effects (especially nausea and diarrhea) were more common than with comparators. Meta-analysis cannot capture individual patient variability. Fasting requirement for oral semaglutide may reduce real-world effectiveness."},{"rthcId":"RPEP-09645","title":"Dipeptidyl peptidase-4 disturbs adipocyte differentiation via the negative regulation of the glucagon-like peptide-1/adiponectin-cathepsin K axis in mice under chronic stress conditions.","authors":"Zhang, Meiping; Yue, Xueling; Xu, Shengnan; Piao, Jinshun; Zhao, Longguo; Shu, Shangzhi; Kuzuya, Masafumi; Li, Ping; Hong, Lan; Kim, Weon; Liu, Bin; Cheng, Xian Wu","year":2024,"journal":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 38(10), e23684","doi":"10.1096/fj.202400158R","pmid":"38795334","tags":["GLP-1-receptor-agonists","DPP-4-inhibitors","weight-management"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"Chronic stress increased DPP-4, decreased GLP-1 levels, and disrupted adipocyte differentiation through the GLP-1/adiponectin-cathepsin K axis. DPP-4 deletion, exenatide treatment, and CTSK deletion all reversed stress-related fat tissue dysfunction.","whyItMatters":"Chronic stress is a growing public health crisis linked to obesity and metabolic disease. This study reveals a specific molecular pathway — DPP-4/GLP-1/adiponectin — connecting psychological stress to fat tissue dysfunction, suggesting that GLP-1 drugs or DPP-4 inhibitors could protect metabolic health during periods of chronic stress.","specificNumbers":"Used three mouse genotypes (DPP4+/+, DPP4-/-, CTSK-/-) to dissect the pathway under stress and non-stress conditions.","methodology":"In vivo study using DPP4+/+, DPP4-/-, and CTSK-/- mice under 2 weeks of chronic psychosocial stress, with exenatide (GLP-1 agonist) intervention. In vitro studies using 3T3-L1 preadipocytes with CTSK silencing/overexpression. Measured plasma DPP4/GLP-1/CTSK/adiponectin, adipose tissue morphology, gene/protein expression, and macrophage infiltration.","limitations":"Mouse chronic stress model may not fully replicate human psychological stress. Two-week duration is relatively short for chronic stress effects. The complex multi-knockout design makes pathway isolation challenging. Fat tissue biology differs between mice and humans."},{"rthcId":"RPEP-09646","title":"The Association between GLP-1 Receptor-Based Agonists and the Incidence of Asthma in Patients with Type 2 Diabetes and/or Obesity: A Meta-Analysis.","authors":"Zhang, Meng Qing; Lin, Chu; Cai, Xiao Ling; Jiao, Ruo Yang; Bai, Shu Zhen; Li, Zong Lin; Hu, Sui Yuan; Lyu, Fang; Yang, Wen Jia; Ji, Li Nong","year":2024,"journal":"Biomedical and environmental sciences : BES, 37(6), 607-616","doi":"10.3967/bes2024.067","pmid":"38988111","tags":["GLP-1-receptor-agonists","respiratory-health","immune-function"],"studyType":"meta-analysis","evidenceStrength":"moderate","keyFinding":"GLP-1 receptor-based agonists showed a non-significant 9% asthma risk reduction overall (RR 0.91, 95% CI 0.68-1.24), but light-molecular-weight GLP-1RAs showed a significant 35% reduction (RR 0.65, 95% CI 0.43-0.99, P=0.043).","whyItMatters":"If GLP-1 drugs can reduce asthma risk in the millions of people taking them for diabetes and obesity, it would be a significant secondary benefit — especially since these conditions frequently overlap and obesity worsens asthma.","specificNumbers":"Meta-analysis pooling data from multiple studies across databases examining GLP-1 RA use and asthma outcomes.","methodology":"Systematic review and meta-analysis of 39 RCTs (85,755 participants) from PubMed, Web of Science, Embase, Cochrane CENTRAL, and ClinicalTrials.gov through July 2023. Used fixed-effects model with subgroup analyses by drug structure, duration, and molecular weight.","limitations":"Overall result was not statistically significant. Asthma was typically an incidental finding in diabetes/obesity trials, not a primary endpoint. Weight loss itself could reduce asthma risk. The significant finding for light-molecular-weight GLP-1RAs may reflect subgroup multiplicity. Different GLP-1 drugs and doses were pooled."},{"rthcId":"RPEP-09647","title":"DeepBP: Ensemble deep learning strategy for bioactive peptide prediction.","authors":"Zhang, Ming; Zhou, Jianren; Wang, Xiaohua; Wang, Xun; Ge, Fang","year":2024,"journal":"BMC bioinformatics, 25(1), 352","doi":"10.1186/s12859-024-05974-5","pmid":"39528950","tags":["bioactive-peptides","peptide-drug-design"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"DeepBP achieved 92.6% balanced accuracy (MCC 0.831, AUC 0.966) for ACE inhibitory peptide prediction and 77.9% accuracy (MCC 0.558) for anticancer peptide prediction, surpassing existing computational methods.","whyItMatters":"Drug discovery typically screens thousands of peptides experimentally. An AI tool that accurately predicts bioactive properties from sequence alone could accelerate peptide drug and functional food ingredient development by dramatically reducing the number of candidates that need laboratory testing.","specificNumbers":"DeepBP uses an ensemble approach combining multiple deep learning models for improved prediction accuracy across bioactive peptide categories.","methodology":"Ensemble deep learning using CapsuleGAN, GRU, and CNN as base classifiers with weighted voting. Features extracted using ESM-2 protein language model. Trained and validated on ACE inhibitory peptide and anticancer peptide datasets. Source code publicly available on GitHub.","limitations":"AI predictions require experimental validation — high computational accuracy does not guarantee real-world bioactivity. Training data may not cover all bioactive peptide types. Performance on rare or novel peptide activities is unknown. The anticancer peptide prediction accuracy (77.9%) leaves room for improvement."},{"rthcId":"RPEP-09648","title":"Crowdsourcing Adverse Events Associated With Monoclonal Antibodies Targeting Calcitonin Gene-Related Peptide Signaling for Migraine Prevention: Natural Language Processing Analysis of Social Media.","authors":"Zhang, Pengfei; Kamitaki, Brad K; Do, Thien Phu","year":2024,"journal":"JMIR formative research, 8, e58176","doi":"10.2196/58176","pmid":"39515814","tags":["CGRP-peptides","neurological-conditions"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"NLP analysis identified \"constipation,\" \"depression,\" \"vomiting,\" and \"muscle\" as recurring erenumab-associated terms on Reddit, while fremanezumab showed no definite adverse event signals — suggesting different real-world tolerability profiles despite targeting the same pathway.","whyItMatters":"Clinical trial participants are highly selected and may not represent the diverse patient populations actually taking CGRP drugs. Social media captures experiences from a broader range of patients, potentially identifying side effects that trials miss — information valuable for both patients and prescribers.","specificNumbers":"Analysis covered social media posts about CGRP-targeting medications, identifying adverse events not fully captured in clinical trials.","methodology":"Computational linguistics analysis of 22,467 posts from Reddit r/Migraine (2010-2020). Compared word frequencies between medication-specific posts and control posts. Validated approach using known adverse events of propranolol and topiramate before applying to erenumab and fremanezumab.","limitations":"Social media data is self-reported and unverified. Negativity bias means adverse experiences are more likely to be posted than positive ones. Small sample for fremanezumab (73 posts) limits conclusions. Keyword associations do not prove causation. Reddit demographics may not represent all migraine patients."},{"rthcId":"RPEP-09649","title":"Liraglutide Promotes Diabetic Wound Healing via Myo1c/Dock5.","authors":"Zhang, Qian; Zhang, Chunlin; Kang, Changjiang; Zhu, Jiaran; He, Qingshan; Li, Hongwei; Tong, Qiang; Wang, Min; Zhang, Linlin; Xiong, Xin; Wang, Yuren; Qu, Hua; Zheng, Hongting; Zheng, Yi","year":2024,"journal":"Advanced science (Weinheim, Baden-Wurttemberg, Germany), 11(39), e2405987","doi":"10.1002/advs.202405987","pmid":"39159301","tags":["GLP-1-receptor-agonists","liraglutide","wound-healing"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"Liraglutide directly binds Myo1c at arginine 93, enhances Myo1c/Dock5 interaction to promote keratinocyte proliferation, migration, and adhesion. Dock5 keratinocyte-specific knockout abolished liraglutide wound-healing benefits.","whyItMatters":"Diabetic foot ulcers lead to over 100,000 amputations per year in the US alone. Liraglutide is already FDA-approved and widely used — discovering that it promotes wound healing through a distinct pathway beyond blood sugar control could immediately expand its clinical applications.","specificNumbers":"Liraglutide significantly accelerated wound closure in both db/db and STZ-induced diabetic mouse models.","methodology":"Wound healing studies in db/db and STZ-induced diabetic mice with liraglutide treatment. Dock5 keratinocyte-specific knockout mice to confirm mechanism. Characterized re-epithelialization, collagen deposition, ECM remodeling, and keratinocyte functions. Identified Myo1c binding site and Dock5 pathway.","limitations":"Mouse wound models differ from human diabetic ulcers in size, healing dynamics, and microenvironment. The optimal dosing route (systemic vs topical) for wound healing is unclear. Human clinical trials are needed. The mechanism involves a non-GLP-1R pathway, which may behave differently across species."},{"rthcId":"RPEP-09650","title":"MMP-2 Responsive Peptide Hydrogel-Based Nanoplatform for Multimodal Tumor Therapy.","authors":"Zhang, Qing; Hu, Wenjun; Guo, Mingxue; Zhang, Xinyu; Zhang, Qin; Peng, Fengqi; Yan, Liwen; Hu, Zucheng; Tangthianchaichana, Jakkree; Shen, Yan; Hu, Haiyan; Du, Shouying; Lu, Yang","year":2024,"journal":"International journal of nanomedicine, 19, 53-71","doi":"10.2147/IJN.S432112","pmid":"38187906","tags":["peptide-drug-delivery","cancer-research"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"The MMP-2 responsive hydrogel achieved 3.5-fold and 5.2-fold increases in CD8+ T cell infiltration in primary and distant tumors respectively, effectively suppressing primary, distant, and recurrent tumor growth through combined photothermal-chemo-immunotherapy.","whyItMatters":"Cancer often requires multiple treatment modalities, but combining them causes severe side effects. A peptide-based platform that activates only at the tumor site delivers triple therapy locally while minimizing systemic toxicity — a major advance in precision oncology.","specificNumbers":"The hydrogel platform combined three therapeutic modalities: photothermal therapy, chemotherapy (bufalin), and immunotherapy in a single MMP-2-responsive system.","methodology":"Designed peptide hydrogel (aP/IR@FMKB) with MMP-2-cleavable and tumor-penetrating peptides. Loaded with bufalin nanoparticles, IR820, and anti-PD-L1. Tested in 4T1 cells (cytotoxicity, ICD induction), 3D spheroids (penetration), and primary/recurrent/distant tumor mouse models.","limitations":"Preclinical mouse study with 4T1 breast cancer model — may not translate to all cancer types. Complex manufacturing could hinder clinical development. Photothermal component requires external near-infrared light, limiting treatment to accessible tumors. Long-term safety and immunological consequences unknown."},{"rthcId":"RPEP-09651","title":"Discovery of novel penetrating peptides able to target human leukemia and lymphoma for enhanced PROTAC delivery.","authors":"Zhang, Qingqing; Liu, Yuying; Zhang, Jie; Li, Yanchen; Wang, Jin; Liu, Nanxin; Zhang, Jie; Pan, Xiaoyan","year":2024,"journal":"European journal of medicinal chemistry, 277, 116734","doi":"10.1016/j.ejmech.2024.116734","pmid":"39094275","tags":["peptide-drug-delivery","cancer-research"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Two novel penetrating peptides (C9C-f(3Bta) and Cyclo-C9C-R) significantly enhanced intracellular PROTAC content in K562 leukemia cells, facilitated Bcr-Abl protein degradation, reduced STAT5 phosphorylation, and promoted apoptosis.","whyItMatters":"PROTACs represent the next frontier of cancer therapy, but their poor cell entry is a major limitation. Cancer-targeting peptides that solve this delivery problem could unlock PROTAC therapy for blood cancers and potentially many other cancer types.","specificNumbers":"Novel penetrating peptides demonstrated enhanced PROTAC delivery specifically into leukemia and lymphoma cells.","methodology":"Designed and screened 26 novel targeted penetrating peptides for leukemia/lymphoma cells. Assessed membrane permeability, cancer targeting, and stability. Combined top candidates with IMA-PROTAC and evaluated anti-proliferative activity, Bcr-Abl degradation, STAT5 signaling, apoptosis, and cell cycle effects. Quantified intracellular PROTAC by HPLC-MRM-MS.","limitations":"In vitro cell culture study using cancer cell lines. In vivo efficacy, pharmacokinetics, and selectivity need demonstration. Peptide stability in blood and tissue penetration in living systems are unknown. The peptide-PROTAC combination approach adds manufacturing complexity."},{"rthcId":"RPEP-09652","title":"Transmembrane modification of tumor vascular targeting peptide A7R as molecular cargo delivery tool.","authors":"Zhang, Qingqing; Yang, Zeyu; Zhang, Jie; Li, Yanchen; Dang, Xintao; Qu, Jingkun; Pan, Xiaoyan; Zhang, Jie","year":2024,"journal":"Bioorganic chemistry, 145, 107240","doi":"10.1016/j.bioorg.2024.107240","pmid":"38412651","tags":["peptide-drug-delivery","cancer-research"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Transmembrane-modified A7R peptide self-assembled into nanoparticles that targeted VEGFR2/NRP-1 on tumor vessels, inhibited angiogenesis, and served as a molecular carrier for therapeutic delivery.","whyItMatters":"Creating a single molecule that both targets tumor vessels and carries drug payloads simplifies cancer drug design and could improve treatment by combining targeting and therapy in one step.","specificNumbers":"A7R (ATWLPPR) was modified with arginine and glutamic acid substitutions, cyclized, and linked to a membrane-permeation sequence.","methodology":"Peptide modification and nanoparticle self-assembly characterization. Tested anti-angiogenic and tumor-targeting properties in cell culture and mouse tumor models.","limitations":"Preclinical study. Self-assembly behavior may differ in human blood. Specific therapeutic payload and dosing not fully optimized. Animal model results may not translate directly."},{"rthcId":"RPEP-09653","title":"Anti-cancer immune effect of human colorectal cancer neoantigen peptide based on MHC class I molecular affinity screening.","authors":"Zhang, Siyu; Huang, Changxin; Li, Yongqiang; Li, Zhaoyang; Zhu, Ying; Yang, Lili; Hu, Haokun; Sun, Quan; Liu, Mengmeng; Cao, Songqiang","year":2024,"journal":"Frontiers in immunology, 15, 1473145","doi":"10.3389/fimmu.2024.1473145","pmid":"39559350","tags":["peptide-drug-design","cancer-research","immune-function"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Neoantigens with MHC molecular affinity variation of 1-4 and HLA Type 1 association showed the highest immunogenicity, activating CD4+/CD8+ T cells and NK cells with 96.6% dendritic cell maturation versus 0.051% in controls.","whyItMatters":"Personalized cancer vaccines are one of the most promising cancer immunotherapy approaches, but identifying the right peptides is a bottleneck. This MHC affinity screening method could make neoantigen vaccine development faster and more reliable, bringing personalized cancer treatment closer to routine clinical use.","specificNumbers":"9-amino-acid neoantigen peptides predicted from whole exome sequencing, screened through in vitro MHC class I molecular affinity simulation.","methodology":"Whole exome sequencing of patient-derived colon cancer cells. In silico 9-amino-acid neoantigen prediction. In vitro dendritic cell-mediated antigen presentation to T cells. Immune response assessed by flow cytometry and ELISpot. MHC affinity variation and HLA typing correlated with immunogenicity.","limitations":"In vitro study — immune responses in a dish may not predict clinical vaccine efficacy. Patient-derived cells from a limited number of cases. The 14-day in vitro T cell expansion may not reflect in vivo kinetics. Manufacturing individual neoantigen vaccines remains complex and expensive."},{"rthcId":"RPEP-09654","title":"The subcommissural organ regulates brain development via secreted peptides.","authors":"Zhang, Tingting; Ai, Daosheng; Wei, Pingli; Xu, Ying; Bi, Zhanying; Ma, Fengfei; Li, Fengzhi; Chen, Xing-Jun; Zhang, Zhaohuan; Zou, Xiaoxiao; Guo, Zongpei; Zhao, Yue; Li, Jun-Liszt; Ye, Meng; Feng, Ziyan; Zhang, Xinshuang; Zheng, Lijun; Yu, Jie; Li, Chunli; Tu, Tianqi; Zeng, Hongkui; Lei, Jianfeng; Zhang, Hongqi; Hong, Tao; Zhang, Li; Luo, Benyan; Li, Zhen; Xing, Chao; Jia, Chenxi; Li, Lingjun; Sun, Wenzhi; Ge, Woo-Ping","year":2024,"journal":"Nature neuroscience, 27(6), 1103-1115","doi":"10.1038/s41593-024-01639-x","pmid":"38741020","tags":["neuropeptides","neurological-conditions"],"studyType":"animal study","evidenceStrength":"strong","keyFinding":"SCO ablation caused severe hydrocephalus and neuronal developmental defects. Three SCO-secreted peptides (thymosin beta 4, thymosin beta 10, NP24) were identified by peptidomics, and their reintroduction rescued developmental defects, establishing the SCO as a peptide-secreting organ essential for brain development.","whyItMatters":"This solves a century-old mystery about one of the brain's most enigmatic structures. The discovery that thymosin peptides regulate brain development could explain some cases of hydrocephalus and neurodevelopmental disorders, and reveals a new peptide signaling system in the central nervous system.","specificNumbers":"Three genes (Sspo, Car3, Spdef) were identified as highly expressed in the SCO; genetic ablation caused brain developmental defects.","methodology":"Transcriptomic comparison of SCO vs non-SCO brain regions. Created three Cre-expressing mouse strains (Sspo, Car3, Spdef promoters) for genetic SCO ablation during embryonic development. Peptidomic analysis of brain ventricular fluid. Rescue experiments with identified peptides.","limitations":"Mouse study — the human SCO regresses after birth but is present during fetal development. Whether the same peptide mechanisms operate in human brain development is unknown. Rescue experiments, while compelling, may not fully replicate the complexity of normal SCO signaling."},{"rthcId":"RPEP-09655","title":"Liraglutide, a glucagon-like peptide-1 receptor agonist, ameliorates inflammation and apoptosis via inhibition of receptor for advanced glycation end products signaling in AGEs induced chondrocytes.","authors":"Zhang, Xianyu; Jiang, Jian; Xu, Jiajia; Chen, Jian; Gu, Yuntao; Wu, Guobao","year":2024,"journal":"BMC musculoskeletal disorders, 25(1), 601","doi":"10.1186/s12891-024-07640-6","pmid":"39080620","tags":["GLP-1-receptor-agonists","liraglutide","joint-and-bone-health"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Liraglutide reduced RAGE expression, suppressed IL-6/IL-12/TNF-α, decreased MMP-1/-3/-13 and ADAMTS-4/-5, preserved aggrecan and collagen II, and reduced chondrocyte apoptosis via GLP-1R activation, with all effects reversed by GLP-1R blockade.","whyItMatters":"Osteoarthritis affects over 500 million people with no disease-modifying treatment. If liraglutide protects cartilage through RAGE suppression, the millions of people already taking GLP-1 drugs for diabetes may be getting unrecognized joint protection.","specificNumbers":"Liraglutide reduced MMP and ADAMTS catabolic enzymes while preserving aggrecan and collagen II anabolic markers in AGE-treated chondrocytes.","methodology":"In vitro study using rat primary chondrocytes treated with AGEs ± liraglutide ± exendin (GLP-1R blocker). Measured inflammatory cytokines (ELISA), catabolic/anabolic gene expression (RT-PCR), RAGE expression (Western blot), and apoptosis (TUNEL, caspase-3, immunofluorescence).","limitations":"In vitro cell culture study — joint cartilage in living organisms is exposed to different mechanical and biological forces. Liraglutide concentrations used may not match what reaches joint tissue from systemic dosing. No animal or human osteoarthritis data. The GLP-1R inhibitor used (exendin) may have partial agonist effects."},{"rthcId":"RPEP-09656","title":"Insights into therapeutic peptides in the cancer-immunity cycle: Update and challenges.","authors":"Zhang, Xiaokun; Wu, Ye; Lin, Jiayi; Lu, Shengxin; Lu, Xinchen; Cheng, Aoyu; Chen, Hongzhuan; Zhang, Weidong; Luan, Xin","year":2024,"journal":"Acta pharmaceutica Sinica. B, 14(9), 3818-3833","doi":"10.1016/j.apsb.2024.05.013","pmid":"39309492","tags":["peptide-drug-design","cancer-research","immune-function"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Therapeutic peptides can enhance cancer immunotherapy by targeting multiple steps of the cancer-immunity cycle, though stability and conformation challenges limit their current clinical efficacy.","whyItMatters":"Many cancer patients do not respond to current immunotherapies. Peptides that can boost multiple steps of anti-cancer immunity could help more patients benefit from immunotherapy while potentially reducing side effects compared to full-size antibody drugs.","specificNumbers":"Review covers peptide applications across all stages of the cancer-immunity cycle, from antigen presentation to tumor killing.","methodology":"Comprehensive narrative review of recent advancements in therapeutic peptides targeting the cancer-immunity cycle, including clinical progress and emerging strategies.","limitations":"Narrative review that may not comprehensively cover all published evidence. Many discussed peptides are in early clinical stages. Stability and delivery challenges acknowledged but not fully resolved."},{"rthcId":"RPEP-09657","title":"Feedforward inhibition of stress by brainstem neuropeptide Y neurons.","authors":"Zhang, Yan; Shen, Jiayi; Xie, Famin; Liu, Zhiwei; Yin, Fangfang; Cheng, Mingxiu; Wang, Liang; Cai, Meiting; Herzog, Herbert; Wu, Ping; Zhang, Zhi; Zhan, Cheng; Liu, Tiemin","year":2024,"journal":"Nature communications, 15(1), 7603","doi":"10.1038/s41467-024-51956-9","pmid":"39217143","tags":["neuropeptide-Y","neurological-conditions","mental-health"],"studyType":"animal study","evidenceStrength":"strong","keyFinding":"NPY neurons in the DRN/vlPAG provide feedforward stress inhibition via projections to PVT and LH. Inhibiting them worsened stress responses; activating them reduced anxiety, restored appetite, and transmitted positive valence in male mice.","whyItMatters":"This reveals the brain's natural stress defense system. Rather than treating anxiety by suppressing stress pathways, future therapies could work by boosting this NPY-based stress resistance system — a fundamentally different and potentially more effective approach.","specificNumbers":"A previously uncharacterized NPY neuronal population was identified in the DRN/vlPAG with anxiolytic (anxiety-reducing) effects.","methodology":"Identified DRN/vlPAG NPY neurons using genetic tools. Optogenetic activation and inhibition during stress paradigms. Behavioral testing for anxiety, feeding, and valence. Circuit mapping of projections to PVT and LH. Male C57BL/6 mice.","limitations":"Studied only in male mice — stress responses differ by sex. Optogenetic tools cannot be directly applied in humans. The human brainstem has similar structures but circuit homology is not proven. Behavioral tests capture limited aspects of complex stress disorders."},{"rthcId":"RPEP-09658","title":"Paeonol and glycyrrhizic acid in combination ameliorate the recurrent nitroglycerin-induced migraine-like phenotype in rats by regulating the GABBR2/TRPM8/PRKACA/TRPV1 pathway.","authors":"Zhang, Yao; Ge, Fei; Luo, Yamin; Ji, Xuenian; Liu, Zijian; Qiu, Yuehua; Hou, Jianchen; Zhou, Ranran; Zhao, Caihong; Xu, Qianwei; Zhang, Shujing; Yu, Xue; Wang, Chunguo; Ge, Dongyu; Meng, Fengxian; Tao, Xiaohua","year":2024,"journal":"Journal of ethnopharmacology, 334, 118464","doi":"10.1016/j.jep.2024.118464","pmid":"38908492","tags":["CGRP-peptides","neurological-conditions"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"PAE + GLY reduced CGRP levels and migraine symptoms by upregulating GAD2/GABBR2, increasing GABA, activating the GABBR2/TRPM8/PRKACA/TRPV1 pathway, and suppressing dural inflammation in a rat chronic migraine model.","whyItMatters":"CGRP is the central peptide target in modern migraine drugs (like erenumab and fremanezumab). Understanding how natural compounds reduce CGRP through upstream pathways could identify new drug targets and validate traditional migraine remedies.","specificNumbers":"The combination treatment targeted GABBR2/TRPM8/PRKACA/TRPV1 pathway components in the nitroglycerin-induced migraine model.","methodology":"Nitroglycerin-induced recurrent migraine rat model. Treated with paeonol + glycyrrhizic acid. Assessed behavioral tests, biomarkers (5-HT, histamine, CGRP), RNA-seq transcriptomics, RT-qPCR, Western blot, ELISA, and immunofluorescence.","limitations":"Rat migraine model using nitroglycerin may not fully replicate human chronic migraine. Traditional medicine compounds are mixtures with variable composition. Specific contributions of each compound need further dissection. No comparison with established CGRP-targeting migraine drugs."},{"rthcId":"RPEP-09659","title":"Sulfonium-Stapled Peptides-Based Neoantigen Delivery System for Personalized Tumor Immunotherapy and Prevention.","authors":"Zhang, Yaping; Jiang, Leying; Huang, Siyong; Lian, Chenshan; Liang, Huiting; Xing, Yun; Liu, Jianbo; Tian, Xiaojing; Liu, Zhihong; Wang, Rui; An, Yuhao; Lu, Fei; Pan, Youdong; Han, Wei; Li, Zigang; Yin, Feng","year":2024,"journal":"Advanced science (Weinheim, Baden-Wurttemberg, Germany), 11(24), e2307754","doi":"10.1002/advs.202307754","pmid":"38605600","tags":["peptide-drug-design","cancer-research","immune-function"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"100% tumor prevention for 11 months without recurrence in the prevention model; 40% complete tumor elimination in established MC-38 colon tumors; potent CTL infiltration into tumor microenvironment; efficient antigen/adjuvant co-delivery to draining lymph nodes.","whyItMatters":"Neoantigen vaccines could potentially cure cancer by training each patient's immune system against their specific tumor. The stapled peptide approach solves the critical delivery problem that has held back neoantigen vaccines in clinical trials.","specificNumbers":"Nano-vaccine stimulated strong tumor-specific T cell responses through enhanced antigen uptake and cross-presentation pathways.","methodology":"Developed sulfonium-stapled peptide-nucleic acid conjugate self-assembling nanoparticles. Tested in prophylactic (tumor prevention) and therapeutic (established tumor) models using MC-38 colon cancer. Assessed lymph node delivery, antigen presentation, TLR signaling, T cell responses, and systemic toxicity.","limitations":"Mouse study — human immune responses are more complex. The MC-38 tumor model is moderately immunogenic, which may favor vaccine approaches. Manufacturing personalized stapled peptide neoparticles for each patient is complex. Only single neoantigen tested in therapeutic model — multi-neoantigen approaches may be needed."},{"rthcId":"RPEP-09660","title":"Semaglutide ameliorates Alzheimer's disease and restores oxytocin in APP/PS1 mice and human brain organoid models.","authors":"Zhang, Yinbing; Tang, Cheng; He, Yao; Zhang, Yingqian; Li, Qinxi; Zhang, Ting; Zhao, Bangcheng; Tong, Aiping; Zhong, Qixing; Zhong, Zhihui","year":2024,"journal":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 180, 117540","doi":"10.1016/j.biopha.2024.117540","pmid":"39405916","tags":["semaglutide","GLP-1-receptor-agonists","oxytocin","neurological-conditions"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"Semaglutide reduced amyloid plaques, p-Tau, and neuroinflammatory markers (GFAP, Iba1) while restoring oxytocin levels in both APP/PS1 mice (with improved cognition) and human AD brain organoids.","whyItMatters":"Alzheimer's has no effective treatment. Semaglutide is already FDA-approved and taken by millions. If it truly protects the brain, it could be repurposed for AD much faster than developing a new drug — and the oxytocin restoration suggests a novel mechanism beyond simple anti-inflammation.","specificNumbers":"Semaglutide improved learning and memory in behavioral tests, reduced amyloid plaque deposition, and restored oxytocin levels in APP/PS1 mice.","methodology":"APP/PS1 transgenic Alzheimer's mice: behavioral testing (learning and memory), immunohistochemistry for amyloid plaques, GFAP, Iba1, and oxytocin. Human AD brain organoids: Aβ, p-Tau, GFAP, and oxytocin measurements after semaglutide treatment.","limitations":"APP/PS1 mice model only familial Alzheimer's (a minority of cases). Human brain organoids lack full brain architecture and connectivity. The mechanism linking semaglutide to oxytocin restoration is not fully explained. Clinical trials in AD patients are needed."},{"rthcId":"RPEP-09661","title":"Optimal dose of oxytocin to improve social impairments and repetitive behaviors in autism spectrum disorders: meta-analysis and dose-response meta-analysis of randomized controlled trials.","authors":"Zhang, Yingying; Zhang, Xiaolu; Huang, Linghong","year":2024,"journal":"Frontiers in psychiatry, 15, 1477076","doi":"10.3389/fpsyt.2024.1477076","pmid":"39944132","tags":["oxytocin","neurological-conditions","mental-health"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Intranasal oxytocin at ≥48 IU/day showed significant improvement in social impairments (SRS) and repetitive behaviors (RBS) in ASD, while lower doses and overall pooled analysis showed no significant effects.","whyItMatters":"No medication currently treats core autism symptoms. If oxytocin works at higher doses, it could become the first drug targeting social impairments and repetitive behaviors — the defining features of ASD.","specificNumbers":"Meta-analysis of RCTs with dose-response modeling to identify optimal intranasal oxytocin dosing for ASD symptom improvement.","methodology":"Systematic review and meta-analysis of 12 RCTs (498 ASD patients) from PubMed, Cochrane Library, Embase, and Web of Science through November 2024. Standard meta-analysis plus dose-response meta-analysis using SRS and RBS as primary outcomes.","limitations":"Moderate heterogeneity across 12 trials in diagnosis criteria, ages, outcome measures, and treatment duration. Small total sample (498 patients). The 48 IU threshold is based on available trial doses and may not be the true optimal dose. Safety at higher chronic doses needs evaluation."},{"rthcId":"RPEP-09662","title":"Effectiveness and safety of pharmacological prophylaxis for chronic migraine: a systematic review and network meta-analysis.","authors":"Zhao, Chengqi; Li, Changxin; Yu, Xueping; Dai, Xiaohong; Zou, Wei","year":2024,"journal":"Journal of neurology, 271(9), 5762-5777","doi":"10.1007/s00415-024-12512-z","pmid":"38910144","tags":["CGRP-peptides","neurological-conditions"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Botulinum toxin A: best efficacy for monthly migraine day reduction (MD 3.88 fewer days). Eptinezumab (CGRP antibody): safest profile (RR 1.09 for adverse events). CGRP mAbs ranked second overall behind botulinum toxin A for combined efficacy and safety.","whyItMatters":"Chronic migraine patients and their doctors need evidence-based guidance for choosing prevention drugs. This comprehensive ranking places CGRP antibodies — the newest drug class — in context with established options, confirming their value especially for patients who prioritize safety.","specificNumbers":"Systematic search through August 1, 2023, identifying eligible RCTs across multiple chronic migraine prevention drug classes.","methodology":"Network meta-analysis of 24 RCTs (8,789 patients) from 4 databases through August 2023. Compared chronic migraine prevention drugs using monthly migraine days, 50% responder rate, MIDAS scores, and adverse events. Ranked interventions using SUCRA.","limitations":"Network meta-analysis relies on indirect comparisons between drugs that were rarely tested head-to-head. Different trials used different populations, definitions, and endpoints. Some drugs had more evidence than others. Topiramate's extremely wide confidence interval (3.18-787.30) indicates imprecise estimation."},{"rthcId":"RPEP-09663","title":"Association of cerebrospinal fluid NPY with peripheral ApoA: a moderation effect of BMI.","authors":"Zhao, Danyang; Han, Xiaoli; Mu, Qingshuang; Wu, Yan; Shan, Ligang; Su, Lidong; Wang, Wenyan; Wang, Pengxiang; Kang, Yimin; Wang, Fan","year":2024,"journal":"Nutrition & metabolism, 21(1), 52","doi":"10.1186/s12986-024-00828-6","pmid":"39054540","tags":["neuropeptide-Y","cardiovascular-health"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"BMI moderates the CSF NPY–peripheral ApoA-I relationship (R²=0.144, β=-0.54, p<0.001). NPY was protective in normal weight (positive ApoA-I association) but a risk factor in overweight/obese (negative ApoA-I association).","whyItMatters":"This reveals that brain neuropeptides do not have fixed effects — their impact on cardiovascular risk depends on metabolic state. This could explain why obesity rewires the brain-heart connection and suggests that weight management may be needed to maintain NPY's protective cardiovascular role.","specificNumbers":"Study examined the NPY-apolipoprotein association across BMI categories, finding significant moderation effects.","methodology":"Cross-sectional study of 190 participants (73 normal weight, 117 overweight/obese). Measured NPY, ghrelin, orexin A, and oxytocin in CSF via lumbar puncture. Blood ApoA-I and ApoB measured peripherally. Moderation analysis by BMI.","limitations":"Cross-sectional design cannot establish causation. CSF sampling is invasive, potentially limiting participant selection. The 190-person sample is moderate. ApoA-I and ApoB are surrogate cardiovascular markers, not clinical outcomes."},{"rthcId":"RPEP-09664","title":"DNA-Mediated Peptide Assembly into Protein Mimics.","authors":"Zhao, Fangzhou; Frandsen, Martin; Capodaglio, Sabrina; Sleiman, Hanadi F","year":2024,"journal":"Journal of the American Chemical Society, 146(3), 1946-1956","doi":"10.1021/jacs.3c08984","pmid":"38226787","tags":["peptide-drug-design","bioactive-peptides"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"DNA templates successfully directed peptide self-assembly into protein-mimicking structures with controlled architecture and functional properties.","whyItMatters":"Natural proteins are powerful biological machines but difficult to design from scratch. DNA-guided peptide assembly offers a programmable shortcut — using DNA's predictable base-pairing to organize peptides into specific arrangements that mimic protein structure and function.","specificNumbers":"Library of protein mimics created with different lengths, sequences, and heptad registers using the DNA-templated assembly approach.","methodology":"DNA nanotechnology combined with peptide chemistry to create DNA-peptide conjugates that self-assemble into defined structures. Characterized assembly behavior, structural properties, and functional capabilities.","limitations":"Proof-of-concept study. The structures created are simpler than natural proteins. Stability in biological environments is a concern. Scale-up and manufacturing challenges remain."},{"rthcId":"RPEP-09665","title":"Human β-defensins: The multi-functional natural peptide.","authors":"Zhao, Haile; Zhao, Shuli; Wang, Simeng; Liu, Ying","year":2024,"journal":"Biochemical pharmacology, 227, 116451","doi":"10.1016/j.bcp.2024.116451","pmid":"39059771","tags":["antimicrobial-peptides-defensins","immune-function"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Human beta-defensins function as multi-purpose peptides beyond antimicrobial activity, with roles in immune modulation, wound healing, reproduction, and cancer defense through diverse receptor interactions and signaling pathways.","whyItMatters":"Antibiotic resistance is a growing crisis. Beta-defensins represent nature's antimicrobial strategy — understanding their multi-functional biology could inspire new treatments for infections, cancer, infertility, and inflammatory diseases.","specificNumbers":"Multiple defensins reviewed across antimicrobial, antiviral, antifungal, and immune-regulatory functions.","methodology":"Narrative review of published literature on human beta-defensin biology, structure, functions, and therapeutic potential.","limitations":"Narrative review that may not capture all evidence. Most therapeutic applications of beta-defensins are preclinical. Translating peptide biology into drugs faces stability and delivery challenges."},{"rthcId":"RPEP-09666","title":"In vitro protein digestive properties and peptidomic characterization of five whole component plant protein beverages using a pepsin-pancreatin model.","authors":"Zhao, Junna; Kong, Xiangzhen; Zhang, Caimeng; Hua, Yufei; Chen, Yeming; Li, Xingfei","year":2024,"journal":"Food research international (Ottawa, Ont.), 196, 115076","doi":"10.1016/j.foodres.2024.115076","pmid":"39614564","tags":["bioactive-peptides"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Quinoa: highest digestibility (80.49%), strongest ACE inhibition (IC50 0.90 mg/mL). Oat released the most bioactive peptide candidates (30.89%). Over 93% of quinoa digested peptides were under 1 kDa. Globular proteins were the primary source of bioactive peptides.","whyItMatters":"As plant-based diets grow, understanding which plant proteins deliver the most health-promoting peptides during digestion helps guide nutritional recommendations. Finding that quinoa and oat produce the most bioactive peptides supports their status as premium plant protein sources.","specificNumbers":"Quinoa: 80.49% digestibility, followed by pea, soybean, chickpea, and oat (79.25-70.89%).","methodology":"In vitro pepsin-pancreatin digestion model. Characterized 5 plant protein beverages for digestibility, amino acid scores (DIAAS), antioxidant activity (DPPH, ABTS), ACE inhibitory activity, and peptidomics using PeptideRanker and BIOPEP database screening.","limitations":"In vitro digestion model may not fully replicate human gut conditions. Bioactive peptide predictions from databases need in vivo validation. Processing methods for plant beverages affect protein structure and digestibility. Individual variation in digestion is not captured."},{"rthcId":"RPEP-09667","title":"Tirzepatide for Weight Reduction in Chinese Adults With Obesity: The SURMOUNT-CN Randomized Clinical Trial.","authors":"Zhao, Lin; Cheng, Zhifeng; Lu, Yibing; Liu, Ming; Chen, Hong; Zhang, Min; Wang, Rui; Yuan, Yuan; Li, Xiaoying","year":2024,"journal":"JAMA, 332(7), 551-560","doi":"10.1001/jama.2024.9217","pmid":"38819983","tags":["tirzepatide","GLP-1-receptor-agonists","GIP","weight-management"],"studyType":"RCT","evidenceStrength":"strong","keyFinding":"Tirzepatide 15 mg: -17.5% body weight at 52 weeks (vs -2.3% placebo, P<0.001). 10 mg: -13.6%. 85.8% achieved ≥5% weight loss with 15 mg. 95.7% trial completion. GI side effects mostly mild-moderate with <5% discontinuation.","whyItMatters":"China has the world's largest population affected by obesity. This JAMA trial establishes tirzepatide as highly effective in Chinese adults, supporting regulatory approval and addressing the growing obesity epidemic in Asia where BMI thresholds differ from Western populations.","specificNumbers":"Phase 3 trial at 29 centers in China, September 2021 to December 2022, in adults with BMI above obesity/overweight thresholds.","methodology":"Randomized, double-blind, placebo-controlled phase 3 trial (SURMOUNT-CN). 210 Chinese adults (BMI ≥28 or ≥24 with comorbidities), randomized 1:1:1 to tirzepatide 10 mg, 15 mg, or placebo weekly for 52 weeks at 29 Chinese centers. ITT analysis. ClinicalTrials.gov NCT05024032.","limitations":"52-week duration does not capture long-term weight maintenance or regain after stopping treatment. Moderate sample size (210 participants). Asian-specific BMI cutoffs (≥24/28) differ from Western definitions (≥25/30). Cost and access in China's healthcare system not addressed. Excludes diabetes patients."},{"rthcId":"RPEP-09668","title":"Liraglutide improves follicle development in polycystic ovary syndrome by inhibiting CXCL10 secretion.","authors":"Zhao, Min; Liao, Baoying; Yun, Chuyu; Qi, Xinyu; Pang, Yanli","year":2024,"journal":"Reproductive biology and endocrinology : RB&E, 22(1), 98","doi":"10.1186/s12958-024-01269-9","pmid":"39107809","tags":["GLP-1-receptor-agonists","liraglutide","reproductive-health"],"studyType":"in vitro","evidenceStrength":"moderate","keyFinding":"Liraglutide improved follicle development and reduced PCOS phenotype in rats by inhibiting NLRP3 inflammasome activation and pyroptosis in ovarian tissue.","whyItMatters":"PCOS affects up to 15% of women of reproductive age. If GLP-1 drugs can improve ovarian function through anti-inflammatory mechanisms, it could offer a new treatment approach for PCOS-related infertility.","specificNumbers":"RNA sequencing identified CXCL10 as a key target reduced by liraglutide in PCOS granulosa cells, confirmed by ELISA in follicular fluid.","methodology":"PCOS rat model treated with liraglutide. Assessed ovarian morphology, follicle development, NLRP3 inflammasome markers, pyroptosis pathway components, and inflammatory cytokines.","limitations":"Rat PCOS model may not fully replicate human disease. Liraglutide doses in rats may not translate directly to clinical doses. No fertility outcome data (mating or pregnancy rates). The contribution of weight loss vs direct anti-inflammatory effects is not separated."},{"rthcId":"RPEP-09669","title":"Design and discovery of a highly potent ultralong-acting GLP-1 and glucagon co-agonist for attenuating renal fibrosis.","authors":"Zhao, Qian; Dong, Jiale; Liu, Han; Chen, Hui; Yu, Huan; Ye, Shuyin; Yu, Shuangjin; Li, Yu; Qiu, Longhui; Song, Nazi; Xu, Hongjiao; Liu, Qi; Luo, Zhiteng; Li, Yuyi; Wang, Rui; Chen, Guodong; Jiang, Xianxing","year":2024,"journal":"Acta pharmaceutica Sinica. B, 14(3), 1283-1301","doi":"10.1016/j.apsb.2023.11.020","pmid":"38486997","tags":["GLP-1-receptor-agonists","glucagon","kidney-function"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"1907-B had 2-3x longer half-life than semaglutide in rats and monkeys, and outperformed semaglutide and glucagon individually in reducing kidney fibrosis in both diabetic (db/db) and non-diabetic (UUO) CKD models through dual GLP-1R/GCGR signaling.","whyItMatters":"CKD affects ~850 million people globally with limited treatment options. A dual agonist that protects kidneys in both diabetic and non-diabetic settings — and lasts longer than current GLP-1 drugs — could transform kidney disease treatment.","specificNumbers":"GLP-1R and GCGR expression was lower in CKD mouse kidneys and correlated with disease severity. Receptor knockdown worsened kidney injury in both db/db and UUO models.","methodology":"GLP-1R/GCGR expression analysis in CKD kidneys. Receptor knockdown studies (genetic and pharmacological). Novel peptide design and characterization. Pharmacokinetic studies in rats and cynomolgus monkeys. Efficacy testing in db/db diabetic nephropathy and UUO kidney fibrosis models. Loss-of-function validation.","limitations":"Mouse models of CKD may not fully replicate human disease. Glucagon receptor activation could theoretically raise blood sugar in non-diabetic patients, though this was not observed. Clinical pharmacokinetics and safety in humans need testing. Manufacturing an ultralong-acting dual agonist peptide may present challenges."},{"rthcId":"RPEP-09670","title":"A wearable osmotic microneedle patch provides high-capacity sustained drug delivery in animal models.","authors":"Zhao, Sheng; Lu, Ziyi; Cai, Ruisi; Wang, Hui; Gao, Shukun; Yang, Changwei; Zhang, Ying; Luo, Bowen; Zhang, Wentao; Yang, Yinxian; Wang, Shenqiang; Sheng, Tao; Wang, Shiqi; You, Jiahuan; Zhou, Ruyi; Ji, Huimin; Gong, Haoning; Ye, Xiao; Yu, Jicheng; Zhu, Hong-Hu; Zhang, Yuqi; Gu, Zhen","year":2024,"journal":"Science translational medicine, 16(775), eadp3611","doi":"10.1126/scitranslmed.adp3611","pmid":"39602507","tags":["peptide-drug-delivery"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"Osmotic microneedle (OMN) patch achieved sustained drug delivery for ≥24 hours in animal models, maintaining stable plasma concentrations without electronic components.","whyItMatters":"Peptide drugs like semaglutide and insulin require injections because they cannot be taken orally in most cases. A painless, wearable patch that delivers peptides continuously could transform patient experience and improve drug effectiveness.","specificNumbers":"Three hollow microneedles with diameters less than 200 micrometers; sustained drug delivery for at least 24 hours.","methodology":"Developed osmotic-driven microneedle patch. Characterized drug release kinetics in vitro. Tested sustained drug delivery and plasma pharmacokinetics in animal models.","limitations":"Animal study — skin thickness and drug absorption differ in humans. Drug loading capacity for larger peptides needs evaluation. Patch adhesion and comfort over 24 hours in real-world conditions not yet tested in humans."},{"rthcId":"RPEP-09671","title":"Charge-guided masking of a membrane-destabilizing peptide enables efficient endosomal escape for targeted intracellular delivery of proteins.","authors":"Zhao, Yan; Jiang, Haolin; Chen, Hang; Yu, Jiazhen; Wang, Luyao; Zhou, Wen; Du, Juanjuan","year":2024,"journal":"Acta pharmaceutica Sinica. B, 14(10), 4478-4492","doi":"10.1016/j.apsb.2024.06.022","pmid":"39525569","tags":["peptide-drug-delivery"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Charge-guided masking creates a pH-responsive peptide that is inactive at normal pH but unmasks in acidic endosomes to disrupt membranes and release cargo, enabling efficient intracellular protein delivery.","whyItMatters":"Many potential protein and peptide drugs cannot reach their intracellular targets because they are trapped and destroyed in endosomes. Solving this \"endosomal escape\" problem could unlock an entire class of previously undevelopable therapies.","specificNumbers":"The system activated at endosomal pH (~5), releasing the protein cargo from endosomal entrapment efficiently.","methodology":"Designed charge-masked membrane-destabilizing peptide. Characterized pH-dependent unmasking and membrane disruption. Tested endosomal escape efficiency and intracellular protein delivery in cell models.","limitations":"Cell culture study — in vivo delivery efficiency, biodistribution, and safety are unknown. The efficiency of endosomal escape may vary across cell types and targets. Scale-up and manufacturing complexity need evaluation."},{"rthcId":"RPEP-09672","title":"A real-world prospective observational study of eptinezumab in Asian patients with migraine.","authors":"Zhao, Yi Jing; Ong, Jonathan Jia Yuan; Sonu, Sumit Kumar; Dang, Jiaojiao; Ng, Chai Ching; Herr, Keira Joann; Bose, Rohini; Jion, Yasmin Idu","year":2024,"journal":"Headache, 64(7), 810-824","doi":"10.1111/head.14737","pmid":"38785386","tags":["CGRP-peptides","neurological-conditions"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Eptinezumab was effective and well-tolerated in Asian migraine patients in real-world clinical practice, with significant improvements in migraine frequency, intensity, and disability.","whyItMatters":"Asian populations represent a large proportion of global migraine sufferers but have been underrepresented in CGRP antibody trials. This first real-world evidence in Asian patients fills a critical knowledge gap and supports treatment access.","specificNumbers":"Prospective real-world study in Asian migraine patients; outcomes aligned with pivotal phase 3 trial efficacy data.","methodology":"Prospective, real-world observational study of eptinezumab in Asian migraine patients. Assessed migraine days, headache intensity, disability scores, and tolerability.","limitations":"Observational study without a control group. Real-world data may reflect selection bias. Short follow-up may not capture long-term outcomes. Sample size and specific Asian populations not detailed in this preview."},{"rthcId":"RPEP-09673","title":"Blood-brain barrier and blood-brain tumor barrier penetrating peptide-drug conjugate as targeted therapy for the treatment of lung cancer brain metastasis.","authors":"Zheng, Meng-Zhu; Yang, Zhan-Qun; Cai, Sun-Li; Zheng, Li-Ting; Xue, Yuan; Chen, Long; Lin, Jian","year":2024,"journal":"Lung cancer (Amsterdam, Netherlands), 196, 107957","doi":"10.1016/j.lungcan.2024.107957","pmid":"39303402","tags":["peptide-drug-delivery","cancer-research"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Brain-penetrating peptide-drug conjugates can cross both the BBB and BBTB to deliver cancer drugs to brain tumors, with several promising candidates in preclinical and early clinical development.","whyItMatters":"Brain tumors like glioblastoma have median survival under 2 years partly because drugs cannot reach them. Peptides that breach the blood-brain barrier could transform brain cancer treatment by enabling targeted drug delivery.","specificNumbers":"Nearly 50% of late-stage lung cancer patients develop brain metastases; the PDC achieved drug accumulation in brain tumor lesions.","methodology":"Narrative review of published literature on BBB/BBTB-penetrating peptide-drug conjugates for brain tumor therapy.","limitations":"Most BBB-penetrating PDCs are in preclinical stages. The barrier properties differ between mouse models and human brains. Brain tumor heterogeneity means no single PDC will work for all cases."},{"rthcId":"RPEP-09674","title":"Recombinant ferritin-based nanoparticles as neoantigen carriers significantly inhibit tumor growth and metastasis.","authors":"Zheng, Wei; Li, Shixiong; Shi, Zhongliang; Su, Kailing; Ding, Yu; Zhang, Luyue; Tang, Qian; Han, Jiani; Zhao, Han; Wang, Fengwei; Zhang, Hongru; Hong, Zhangyong","year":2024,"journal":"Journal of nanobiotechnology, 22(1), 562","doi":"10.1186/s12951-024-02837-2","pmid":"39272180","tags":["peptide-drug-delivery","cancer-research","immune-function"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"Ferritin-based nanoparticles significantly enhanced neoantigen-specific immune responses compared to free peptide delivery, improving anti-tumor T cell activation.","whyItMatters":"Neoantigen cancer vaccines are one of the most promising immunotherapy approaches but have been limited by weak immune activation. A simple nanoparticle carrier that amplifies the response could make personalized cancer vaccines practical.","specificNumbers":"Neoantigen-FN nanoparticles successfully activated antigen-specific T cells and inhibited both tumor growth and metastasis.","methodology":"Engineered recombinant ferritin nanoparticles displaying neoantigen peptides. Compared immune responses to free peptides vs ferritin-displayed peptides in tumor models. Assessed T cell activation, tumor infiltration, and anti-tumor efficacy.","limitations":"Preclinical study in animal tumor models. Manufacturing patient-specific ferritin-neoantigen particles at scale remains challenging. Not all neoantigens may display well on ferritin surfaces."},{"rthcId":"RPEP-09675","title":"Assessment of the antimicrobial and immunomodulatory activity of QS-CATH, a promising therapeutic agent isolated from the Chinese spiny frogs (Quasipaa spinosa).","authors":"Zheng, Wei-Cheng; Cheng, Xiao-Yun; Tao, Yu-Hui; Mao, Yue-Song; Lu, Cheng-Pu; Lin, Zhi-Hua; Chen, Jie","year":2024,"journal":"Comparative biochemistry and physiology. Toxicology & pharmacology : CBP, 283, 109943","doi":"10.1016/j.cbpc.2024.109943","pmid":"38810897","tags":["antimicrobial-peptides-defensins","immune-function"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"QS-CATH demonstrated both direct antimicrobial activity against drug-resistant bacteria and immunomodulatory effects, enhancing immune cell responses in a dual-action mechanism.","whyItMatters":"Antibiotic resistance kills over 1.2 million people annually. Peptides like QS-CATH that both kill bacteria directly and boost the immune system offer a two-pronged defense that is much harder for bacteria to develop resistance against.","specificNumbers":"QS-CATH amino acid sequence was predicted from Quasipaa spinosa skin transcriptome and validated for dual antimicrobial/immunomodulatory activity.","methodology":"Assessed QS-CATH antimicrobial activity against multiple bacterial strains including drug-resistant isolates. Evaluated immunomodulatory effects on immune cells. Characterized mechanism of action.","limitations":"In vitro study — in vivo efficacy, safety, and pharmacokinetics need testing. Peptide stability in the body remains a challenge. Manufacturing costs for peptide antimicrobials are higher than traditional antibiotics."},{"rthcId":"RPEP-09676","title":"Role of plasma neuropeptide Y in acute myocardial infarction: a case-control study.","authors":"Zheng, Yan-Li; Lin, Hui-Li; Li, Yue-Ting; Li, Mei-Mei; Du, Jing-Ru; Wang, Wan-da; Wang, Yao-Guo; Cai, Yin-Lian","year":2024,"journal":"BMC cardiovascular disorders, 24(1), 692","doi":"10.1186/s12872-024-04373-1","pmid":"39616326","tags":["neuropeptide-Y","cardiovascular-health"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Plasma NPY was significantly elevated in acute myocardial infarction patients vs controls, with levels correlating with cardiac damage severity.","whyItMatters":"Rapid and accurate heart attack diagnosis saves lives. If NPY provides complementary diagnostic information beyond traditional markers like troponin, it could improve early detection and risk stratification.","specificNumbers":"128 acute MI cases and 62 controls; cases sub-grouped into SYNTAX ≤22, 23-32, and ≥33 categories.","methodology":"Case-control study comparing plasma NPY levels between acute MI patients and matched healthy controls. Assessed correlation with cardiac injury markers and clinical outcomes.","limitations":"Case-control design cannot prove causation. NPY elevation could reflect general stress rather than specific cardiac damage. Small sample size typical of biomarker discovery studies. Clinical utility requires validation in larger prospective studies."},{"rthcId":"RPEP-09677","title":"Wound microenvironment-responsive dually cross-linked nanofibrillar peptide hydrogels for efficient hemostatic control and multi-faceted wound management.","authors":"Zheng, Yaxin; Sun, Lu; Zhai, Ziran; Cao, Fangling; Zhang, Tingting; Jiao, Qishu; Xu, Keming; Zhong, Wenying","year":2024,"journal":"International journal of biological macromolecules, 259(Pt 1), 129133","doi":"10.1016/j.ijbiomac.2023.129133","pmid":"38171439","tags":["bioactive-peptides","wound-healing"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Dual cross-linked nanofibrillar peptide hydrogel provided wound microenvironment-responsive drug release while maintaining structural support for tissue regeneration.","whyItMatters":"Chronic wounds affect millions and cost billions in healthcare. A smart peptide dressing that adapts to the wound environment could provide better healing than passive bandages or conventional wound care.","specificNumbers":"The hydrogel contained the peptide IDM-1 (indomethacin-Gly-Phe-Phe-Tyr-Gly-Arg-Gly-Asp) with dual crosslinking for mechanical strength and responsiveness.","methodology":"Designed self-assembling peptide hydrogel with dual cross-linking. Characterized nanofiber structure, responsiveness to wound conditions, drug release profiles, and wound healing efficacy.","limitations":"Preclinical study. Wound models may not capture the complexity of human chronic wounds. Manufacturing scalability and cost of peptide hydrogels need assessment."},{"rthcId":"RPEP-09678","title":"The Glucagon-Like Peptide-1 (GLP-1) Receptor Agonist Liraglutide Regulates Sirtuin-1-Mediated Neutrophil Extracellular Traps to Improve Diabetes-Induced Bone Metabolism Imbalance.","authors":"Zhong, Shuai; Huang, Liangzhi; Lin, Tingting; Li, Yanyan; Deng, Bin; Kong, Dezhi; Liao, Zhanlin; Huang, Zugui","year":2024,"journal":"Iranian journal of pharmaceutical research : IJPR, 23(1), e148139","doi":"10.5812/ijpr-148139","pmid":"40066121","tags":["GLP-1-receptor-agonists","liraglutide","joint-and-bone-health"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Liraglutide activated the Sirtuin-1 pathway in osteoblasts, protecting them from oxidative stress and promoting bone cell survival and function.","whyItMatters":"Osteoporosis causes millions of fractures annually. If liraglutide protects bones through SIRT1 activation, the millions of people taking GLP-1 drugs may be getting unrecognized bone protection.","specificNumbers":"Diabetic rats showed improved bone metabolism markers and reduced NET formation after liraglutide treatment through SIRT1 activation.","methodology":"In vitro and/or in vivo study examining liraglutide effects on osteoblast function, SIRT1 pathway activation, and protection from oxidative stress-induced bone cell damage.","limitations":"Primarily preclinical evidence. The doses achieving bone protection may differ from clinical metabolic doses. Whether the bone benefits translate to fracture reduction in humans is unknown."},{"rthcId":"RPEP-09679","title":"Subcutaneous BNP Injections in Rabbits: A Novel Approach to Mitigate Myocardial Remodeling in Atrial Fibrillation.","authors":"Zhong, Si; He, Rui; Yu, Jia; Zhao, Hongyan","year":2024,"journal":"Discovery medicine, 36(190), 2182-2190","doi":"10.24976/Discov.Med.202436190.200","pmid":"39600273","tags":["natriuretic-peptides","cardiovascular-health"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Subcutaneous BNP injections significantly reduced myocardial infarction size in rabbits, demonstrating that a simpler delivery route can achieve cardioprotective peptide effects.","whyItMatters":"BNP has known cardioprotective properties but is typically given IV in hospitals. A subcutaneous approach could enable pre-hospital cardioprotection — potentially by paramedics or even self-administration — to reduce heart attack damage before reaching the hospital.","specificNumbers":"BNP administered at 20 μg/kg/day subcutaneously twice daily for three weeks in rapid pacing-induced AF rabbits.","methodology":"Rabbit ischemia model with subcutaneous BNP injections given before and during ischemic insult. Measured infarct size, cardiac function, and damage biomarkers.","limitations":"Rabbit model — human cardiac physiology and BNP pharmacokinetics may differ. Optimal timing, dose, and number of injections need optimization. Safety of exogenous BNP in acutely ill cardiac patients needs evaluation."},{"rthcId":"RPEP-09680","title":"Cathelicidin-BF regulates the AMPK/SIRT1/NF-κB pathway to ameliorate murine osteoarthritis: In vitro and in vivo studie.","authors":"Zhou, Hao; Zou, Linfang; Ren, Hui; Shen, Zhenyu; Lin, Yuanqu; Cai, Haikang; Zhang, Jingdong","year":2024,"journal":"International immunopharmacology, 134, 112201","doi":"10.1016/j.intimp.2024.112201","pmid":"38718660","tags":["antimicrobial-peptides-defensins","joint-and-bone-health"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"Cathelicidin-BF ameliorated osteoarthritis by activating AMPK/SIRT1 and inhibiting NF-κB, reducing joint inflammation and cartilage damage in a murine OA model.","whyItMatters":"Osteoarthritis has no disease-modifying treatment. A natural antimicrobial peptide that reduces joint inflammation through a metabolic pathway (AMPK/SIRT1) could lead to new OA therapies.","specificNumbers":"BF-30 activated the AMPK/SIRT1 pathway and inhibited NF-κB in both cell culture and animal OA models.","methodology":"Mouse osteoarthritis model treated with cathelicidin-BF. Assessed joint pathology, inflammatory markers, and AMPK/SIRT1/NF-κB pathway components.","limitations":"Mouse OA model may not fully replicate human disease. Cathelicidin-BF is snake-derived and would need modification for human use. Optimal dosing and delivery route for joint protection not established."},{"rthcId":"RPEP-09681","title":"Stimuli-responsive peptide hydrogels for biomedical applications.","authors":"Zhou, Haoran; Zhu, Yanhua; Yang, Bingbing; Huo, Yehong; Yin, Yuanyuan; Jiang, Xuemei; Ji, Wei","year":2024,"journal":"Journal of materials chemistry. B, 12(7), 1748-1774","doi":"10.1039/d3tb02610h","pmid":"38305498","tags":["bioactive-peptides","peptide-drug-delivery"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Peptide hydrogels can be engineered to respond to pH, temperature, enzymes, light, and other stimuli, enabling on-demand drug release and dynamic tissue engineering scaffolds.","whyItMatters":"Static drug delivery systems release drugs at a fixed rate regardless of need. Responsive peptide hydrogels deliver drugs when and where they are needed — a fundamental shift toward precision medicine.","specificNumbers":"Review covers multiple stimuli types (thermal, pH, enzymatic, light, redox) and diverse biomedical applications.","methodology":"Comprehensive review of stimuli-responsive peptide hydrogel design principles, stimulus types, and biomedical applications.","limitations":"Review covers a broad field with many approaches at varying development stages. Most responsive hydrogels are in preclinical stages. Scale-up and regulatory pathways for smart biomaterials remain challenging."},{"rthcId":"RPEP-09682","title":"Aflibercept Loaded Eye-Drop Hydrogel Mediated with Cell-Penetrating Peptide for Corneal Neovascularization Treatment.","authors":"Zhou, Jianan; Cai, Yuting; Li, Tingting; Zhou, Haixiang; Dong, Huilei; Wu, Xia; Li, Zenghui; Wang, Wenjie; Yuan, Dan; Li, Yun; Shi, Junfeng","year":2024,"journal":"Small (Weinheim an der Bergstrasse, Germany), 20(2), e2302765","doi":"10.1002/smll.202302765","pmid":"37679056","tags":["peptide-drug-delivery"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Cell-penetrating peptide-mediated eye drop hydrogel successfully delivered aflibercept across the corneal barrier, reducing neovascularization without injection.","whyItMatters":"Eye injections are painful, carry infection risk, and require clinic visits. An eye drop that delivers the same anti-VEGF drugs using peptide technology could transform ophthalmic treatment and improve patient compliance.","specificNumbers":"Gel 2_1&Eylea showed superior membrane permeability, increased stability, and prolonged drug contact time compared to standard formulations.","methodology":"Developed CPP-aflibercept eye drop hydrogel formulation. Characterized corneal penetration and drug release. Tested efficacy in corneal neovascularization model.","limitations":"Preclinical study. Corneal drug delivery does not guarantee reaching the retina for diseases like macular degeneration. CPP-protein stability in eye drop formulations needs long-term evaluation."},{"rthcId":"RPEP-09683","title":"Exploration of the potential association between GLP-1 receptor agonists and suicidal or self-injurious behaviors: a pharmacovigilance study based on the FDA Adverse Event Reporting System database.","authors":"Zhou, Jianxing; Zheng, You; Xu, Baohua; Long, Songjun; Zhu, Li-E; Liu, Yunhui; Li, Chengliang; Zhang, Yifan; Liu, Maobai; Wu, Xuemei","year":2024,"journal":"BMC medicine, 22(1), 65","doi":"10.1186/s12916-024-03274-6","pmid":"38355513","tags":["GLP-1-receptor-agonists","mental-health"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"No significant association was found between GLP-1 receptor agonist use and suicidal ideation or behavior in this systematic analysis.","whyItMatters":"Millions of people take GLP-1 drugs, and regulatory agencies have investigated suicide concerns. Finding no significant risk provides important safety reassurance and supports continued prescribing confidence.","specificNumbers":"FAERS data analyzed from Q1 2018 through Q4 2022, covering the period of rapid GLP-1RA adoption.","methodology":"Systematic analysis of clinical trial data and pharmacovigilance reports examining the association between GLP-1 receptor agonists and suicidal ideation/behavior.","limitations":"Suicidal ideation is often underreported in clinical trials. Pharmacovigilance databases have reporting biases. Patients with pre-existing psychiatric conditions may have been underrepresented in GLP-1 trials. The analysis may lack power to detect very rare events."},{"rthcId":"RPEP-09684","title":"Cell-free adipose tissue extracts as a novel treatment for rosacea by downregulating TRPV1.","authors":"Zhou, Liuyi; Chen, Lulu; Li, Ting; Wang, Lu; Lin, Shiqi; Zhao, Ye; Wu, Sufan; Jin, Tingting","year":2024,"journal":"Scientific reports, 14(1), 21759","doi":"10.1038/s41598-024-72593-8","pmid":"39294294","tags":["skin-health","bioactive-peptides"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"ATEs downregulated TRPV1 expression, reduced LL-37-induced inflammatory markers (KLK5, IL-6, IL-8, TNF-α), and improved all clinical rosacea symptoms including erythema, transepidermal water loss, epidermal thickness, mast cells, and telangiectasia.","whyItMatters":"This connects the cathelicidin LL-37 rosacea pathway to a novel treatment approach. Understanding that fat-derived factors can suppress TRPV1 — the receptor that amplifies rosacea inflammation — opens a new therapeutic strategy using the body's own healing molecules.","specificNumbers":"ATEs containing growth factors successfully reduced TRPV1 expression associated with rosacea symptoms.","methodology":"LL-37-induced rosacea mouse model and capsaicin-stimulated HaCaT keratinocytes treated with ATEs. Assessed TRPV1 expression, calcium influx, inflammatory cytokines, erythema scores, TEWL, epidermal thickness, mast cell infiltration, CD31 expression, and biocompatibility.","limitations":"Preclinical study in mice. ATE composition varies between donors and preparations, making standardization challenging. Long-term effects and optimal dosing not established. Human clinical trials needed."},{"rthcId":"RPEP-09685","title":"Exenatide reduces atrial fibrillation susceptibility by inhibiting hKv1.5 and hNav1.5 channels.","authors":"Zhou, Qian; Hao, Guoliang; Xie, Wensen; Chen, Bin; Lu, Wuguang; Wang, Gongxin; Zhong, Rongling; Chen, Jiao; Ye, Juan; Shen, Jianping; Cao, Peng","year":2024,"journal":"The Journal of biological chemistry, 300(5), 107294","doi":"10.1016/j.jbc.2024.107294","pmid":"38636665","tags":["GLP-1-receptor-agonists","exenatide","cardiovascular-health"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Exenatide directly inhibited hKv1.5 and hNav1.5 cardiac ion channels, reducing atrial fibrillation susceptibility through electrophysiological modification of atrial cells.","whyItMatters":"AFib affects 60+ million people and increases stroke risk. Understanding that GLP-1 drugs directly stabilize heart electrical activity — not just indirectly through weight loss — could lead to new anti-arrhythmic applications.","specificNumbers":"Exenatide inhibited both hKv1.5 (potassium) and hNav1.5 (sodium) channels as measured by whole-cell patch-clamp electrophysiology.","methodology":"Electrophysiology studies (patch clamp) measuring exenatide effects on hKv1.5 and hNav1.5 channel currents in cardiac cells. Assessed atrial fibrillation susceptibility.","limitations":"In vitro electrophysiology study. Ion channel effects in isolated cells may not fully predict clinical anti-arrhythmic efficacy. The specific doses achieving these effects may differ from clinical GLP-1 doses."},{"rthcId":"RPEP-09686","title":"Configuration of two cysteine residues in a ring within a stapled Bim peptide affects the secondary structure and apoptotic activity.","authors":"Zhou, Shengli; Nishimura, Fuka; Wada, Kazuhaya; Fujii, Kaho; Kondo, Takeshi; Watanabe, Kazunori; Imai, Yoshitane; Ohtsuki, Takashi; Kitamatsu, Mizuki","year":2024,"journal":"Bioorganic & medicinal chemistry letters, 112, 129915","doi":"10.1016/j.bmcl.2024.129915","pmid":"39127242","tags":["peptide-drug-design"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Cysteine configuration within the staple ring of a Bim peptide significantly impacted its ability to bind target proteins and induce cancer cell apoptosis.","whyItMatters":"Stapled peptides are a major drug development platform, but design rules are still being established. Understanding how staple chemistry affects function enables better rational design of peptide cancer drugs.","specificNumbers":"Four cysteine configuration variants tested for helix content and apoptotic activity, with significant differences observed.","methodology":"Synthesized stapled Bim peptides with different cysteine configurations. Assessed binding affinity, helicity, cellular uptake, and apoptosis induction in cancer cells.","limitations":"Focused on one specific peptide (Bim). Configuration effects may differ for other peptide sequences. In vitro cancer cell results need in vivo validation."},{"rthcId":"RPEP-09687","title":"An amphibian-derived cathelicidin accelerates cutaneous wound healing through its main regulatory effect on phagocytes.","authors":"Zhou, Xiaoyan; Shen, Huan; Wu, Shuxin; Mu, Lixian; Yang, Hailong; Wu, Jing","year":2024,"journal":"International immunopharmacology, 129, 111595","doi":"10.1016/j.intimp.2024.111595","pmid":"38295541","tags":["antimicrobial-peptides-defensins","wound-healing"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Amphibian-derived cathelicidin accelerated wound healing by promoting immune cell migration and tissue repair, demonstrating dual antimicrobial and regenerative properties.","whyItMatters":"Chronic wounds and wound infections are major healthcare problems. A peptide that both kills bacteria and actively accelerates healing addresses both challenges simultaneously.","specificNumbers":"29-residue peptide BugaCATH identified from Bufo gargarizans skin; no direct antimicrobial effects but significant wound healing acceleration through phagocyte regulation.","methodology":"Characterized amphibian cathelicidin peptide for antimicrobial and wound-healing activities. Assessed immune cell migration, wound closure rates, and tissue repair in wound models.","limitations":"Preclinical wound study. Amphibian-derived peptides may need modification for human use. Stability, immunogenicity, and manufacturing challenges need assessment."},{"rthcId":"RPEP-09688","title":"Tumor targeting peptide TMTP1 modified Antigen capture Nano-vaccine combined with chemotherapy and PD-L1 blockade effectively inhibits growth of ovarian cancer.","authors":"Zhou, Ying; Wei, Rui; Wang, Ling; Li, Jie; Wang, Wei; Jiang, Guiying; Tan, Songwei; Li, Fei; Wang, Xueqian; Ma, Xiangyi; Xi, Ling","year":2024,"journal":"Journal of nanobiotechnology, 22(1), 483","doi":"10.1186/s12951-024-02744-6","pmid":"39138475","tags":["peptide-drug-delivery","cancer-research","immune-function"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"TMTP1-modified antigen-capture nano-vaccine combined with anti-PD-1 significantly enhanced anti-tumor immune responses through improved antigen capture and T cell activation.","whyItMatters":"Checkpoint immunotherapy works for some patients but many do not respond. A peptide-targeted nano-vaccine that improves antigen presentation could convert non-responders into responders by better priming their immune system.","specificNumbers":"Triple combination (TMTP1 nano-vaccine + chemotherapy + PD-L1 blockade) significantly inhibited ovarian cancer growth in preclinical models.","methodology":"Developed TMTP1-modified antigen-capture nanoparticles. Combined with anti-PD-1 checkpoint immunotherapy. Assessed antigen capture efficiency, T cell activation, and anti-tumor efficacy in tumor models.","limitations":"Preclinical study. The combination approach adds complexity and cost. TMTP1 targeting may vary across tumor types. Human immune responses may differ."},{"rthcId":"RPEP-09689","title":"Comprehensively prognostic and immunological analyses of GLP-1 signaling-related genes in pan-cancer and validation in colorectal cancer.","authors":"Zhu, Chaojun; Lai, Yihong; Liu, Chengdong; Teng, Lan; Zhu, Yuxin; Lin, Xinyu; Fu, Xinyi; Lai, Qiuhua; Liu, Side; Zhou, Xiaohan; Fang, Yuxin","year":2024,"journal":"Frontiers in pharmacology, 15, 1387243","doi":"10.3389/fphar.2024.1387243","pmid":"39104385","tags":["GLP-1-receptor-agonists","cancer-research"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"GLP-1 signaling genes predicted cancer prognosis and correlated with tumor immune microenvironment composition across multiple cancer types.","whyItMatters":"As GLP-1 drugs are prescribed to millions for diabetes and obesity, understanding their relationship to cancer — through genomic and immunological analysis — is essential for long-term safety assessment and may reveal new cancer treatment opportunities.","specificNumbers":"Comprehensive analysis across pan-cancer datasets with specific validation in colorectal cancer.","methodology":"Bioinformatics analysis of GLP-1 signaling-related genes across multiple cancer genomic databases. Assessed prognostic significance, immune cell infiltration patterns, and pathway enrichment.","limitations":"Bioinformatics analysis based on gene expression correlations, not causation. Genomic data cannot determine whether GLP-1 drugs themselves affect cancer outcomes. Results need experimental validation."},{"rthcId":"RPEP-09690","title":"Enhanced neuroprotective activity of ophthalmic delivered nerve growth factor conjugated with cell penetrating peptide against optic nerve injury.","authors":"Zhu, Danni; Li, Yao; Zhang, Jinlong; Chen, Yi; Song, Xiaohong; Chen, Wei; Wu, Shipo; Hou, Lihua","year":2024,"journal":"Journal of drug targeting, 32(1), 93-99","doi":"10.1080/1061186X.2023.2295220","pmid":"38105766","tags":["peptide-drug-delivery","neurological-conditions"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"CPP-conjugated NGF delivered ophthalmically showed enhanced neuroprotective activity compared to NGF alone, leveraging the eye-brain connection for non-invasive brain drug delivery.","whyItMatters":"Neurodegenerative diseases like Alzheimer's and Parkinson's have no cure. Eye drops that deliver neuroprotective proteins to the brain via peptide technology could make treatment accessible and non-invasive.","specificNumbers":"L-PenetraMax significantly enhanced NGF delivery efficiency to the optic nerve through topical ophthalmic administration.","methodology":"Combined NGF with cell-penetrating peptide. Formulated as ophthalmic delivery. Assessed ocular penetration, brain delivery, and neuroprotective activity.","limitations":"Preclinical study. The amount of NGF reaching the brain via eye drops may be limited. Long-term safety of repeated CPP-protein eye administration needs evaluation."},{"rthcId":"RPEP-09691","title":"An Advanced Intrahepatic Cholangiocarcinoma Patient Benefits from Personalized Immunotherapy.","authors":"Zhu, Sihui; Liu, Chenxi; Jin, Yunchen; Zhang, Hailong; Zhou, Mingzhen; Xu, Chen; Shao, Jie; Liu, Qin; Wei, Jia; Shen, Jie; Liu, Baorui","year":2024,"journal":"Inflammation, 47(5), 1699-1705","doi":"10.1007/s10753-024-02003-8","pmid":"38492185","tags":["peptide-drug-design","cancer-research","immune-function"],"studyType":"case series","evidenceStrength":"preliminary","keyFinding":"Personalized neoantigen peptide immunotherapy induced tumor-specific immune responses and clinical benefit in a patient with advanced intrahepatic cholangiocarcinoma.","whyItMatters":"Rare cancers like cholangiocarcinoma are often excluded from clinical trials. Personalized neoantigen vaccines offer a treatment approach that works for any cancer type, potentially transforming care for rare cancer patients.","specificNumbers":"Overall survival for advanced ICC is less than 1 year with standard treatments; this patient showed benefit from personalized immunotherapy.","methodology":"Case report: whole exome sequencing to identify tumor neoantigens, peptide vaccine design, immunotherapy administration, and assessment of immune responses and clinical outcomes.","limitations":"Single case report — the weakest form of evidence. Response may not be generalizable. Manufacturing individual neoantigen vaccines is time-consuming and expensive."},{"rthcId":"RPEP-09692","title":"Novel enzyme-resistant pancreatic polypeptide analogs evoke pancreatic beta-cell rest, enhance islet cell turnover, and inhibit food intake in mice.","authors":"Zhu, Wuyun; Tanday, Neil; Lafferty, Ryan A; Flatt, Peter R; Irwin, Nigel","year":2024,"journal":"BioFactors (Oxford, England), 50(6), 1101-1112","doi":"10.1002/biof.2059","pmid":"38635341","tags":["neuropeptide-Y","diabetes","weight-management"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Novel enzyme-resistant pancreatic polypeptide analogs promoted pancreatic beta cell proliferation, offering a potential peptide-based approach to restoring insulin-producing cell mass.","whyItMatters":"Diabetes fundamentally involves loss of insulin-producing beta cells. Finding a peptide that stimulates beta cell growth could enable regenerative treatments that restore the body's own insulin production — a cure-level approach.","specificNumbers":"Five novel analogs designed with amino acid substitutions and fatty acid derivatization for enhanced stability and NPY4R activation.","methodology":"Designed and synthesized enzyme-resistant PP analogs. Assessed enzymatic stability, receptor binding, and effects on pancreatic beta cell proliferation and function.","limitations":"Preclinical study. Beta cell proliferation in lab conditions may not translate to in vivo regeneration. Safety of chronic PP analog administration, especially effects on appetite and other NPY pathways, needs evaluation."},{"rthcId":"RPEP-09693","title":"Predicting responsiveness to GLP-1 pathway drugs using real-world data.","authors":"Zhu, Xiaodong; Fowler, Michael J; Wells, Quinn S; Stafford, John M; Gannon, Maureen","year":2024,"journal":"BMC endocrine disorders, 24(1), 269","doi":"10.1186/s12902-024-01798-9","pmid":"39695549","tags":["GLP-1-receptor-agonists","DPP-4-inhibitors","diabetes"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Machine learning models using real-world data successfully predicted individual patient responsiveness to GLP-1 pathway drugs, enabling more targeted treatment selection.","whyItMatters":"Choosing the right diabetes drug for each patient is currently trial-and-error. AI-powered prediction could match patients to GLP-1 drugs more efficiently, saving time and improving outcomes.","specificNumbers":"Model built on real-world data covering both GLP-1 receptor agonists and DPP-4 inhibitors.","methodology":"Retrospective analysis of real-world clinical data. Developed and validated machine learning prediction models for GLP-1 RA and DPP-4 inhibitor responsiveness based on patient characteristics and biomarkers.","limitations":"Real-world data is messy with confounders and missing variables. Model predictions may not generalize to all populations. Treatment response is influenced by many unmeasured factors including adherence and lifestyle."},{"rthcId":"RPEP-09694","title":"Identification, screening and molecular mechanisms of natural stable angiotensin-converting enzyme (ACE) inhibitory peptides from foxtail millet protein hydrolysates: a combined in silico and in vitro study.","authors":"Zhu, Yiqing; Chen, Changyu; Dai, Zijian; Wang, Han; Zhang, Yiyun; Zhao, Qingyu; Xue, Yong; Shen, Qun","year":2024,"journal":"Food & function, 15(15), 7782-7793","doi":"10.1039/d4fo01992j","pmid":"38967438","tags":["bioactive-peptides","cardiovascular-health"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Identified natural ACE-inhibitory peptides that maintain stability through digestion, with molecular characterization of their ACE binding and inhibition mechanisms.","whyItMatters":"Hypertension affects 1.3 billion people. Natural peptides that lower blood pressure through ACE inhibition — and survive digestion — could become dietary supplements or functional foods for blood pressure management.","specificNumbers":"Five specific peptide sequences identified: QDPLFPL, FPGVSPF, SPAQLLPF, LVPYRP, and WYWPQ, all showing ACE inhibition and processing stability.","methodology":"Systematic identification of ACE-inhibitory peptides. Assessed digestive stability using in vitro gastrointestinal models. Molecular modeling of ACE-peptide interactions. Characterized inhibition kinetics.","limitations":"In vitro study — in vivo blood pressure effects need confirmation. Digestive stability in test tubes may not perfectly reflect human digestion. Bioavailability after intestinal absorption is unknown."},{"rthcId":"RPEP-09695","title":"Sympathetic neuropeptide Y protects from obesity by sustaining thermogenic fat.","authors":"Zhu, Yitao; Yao, Lu; Gallo-Ferraz, Ana L; Bombassaro, Bruna; Simões, Marcela R; Abe, Ichitaro; Chen, Jing; Sarker, Gitalee; Ciccarelli, Alessandro; Zhou, Linna; Lee, Carl; Sidarta-Oliveira, Davi; Martínez-Sánchez, Noelia; Dustin, Michael L; Zhan, Cheng; Horvath, Tamas L; Velloso, Licio A; Kajimura, Shingo; Domingos, Ana I","year":2024,"journal":"Nature, 634(8032), 243-250","doi":"10.1038/s41586-024-07863-6","pmid":"39198648","tags":["neuropeptide-Y","weight-management"],"studyType":"animal study","evidenceStrength":"strong","keyFinding":"Sympathetic nerve-derived NPY sustained thermogenic brown and beige fat, with its loss leading to reduced thermogenesis and increased obesity — opposite to NPY's pro-obesity role in the brain.","whyItMatters":"Understanding that NPY has opposite metabolic effects in different tissues (brain: weight gain vs. sympathetic: weight protection) fundamentally changes how we think about this peptide and could lead to tissue-targeted anti-obesity therapies.","specificNumbers":"NPY+ sympathetic axons are a smaller subset mapping to perivasculature; mural cells identified as main NPY-responsive cells by scRNA-seq.","methodology":"Characterized sympathetic NPY signaling in thermogenic fat tissue. Used genetic models to disrupt sympathetic NPY and assessed effects on brown/beige fat, thermogenesis, and body weight.","limitations":"Mouse study — sympathetic NPY roles in human thermogenic fat may differ. The balance between central and peripheral NPY effects in human obesity is poorly understood."},{"rthcId":"RPEP-09696","title":"Substance P Promotes Leukocyte Infiltration in the Liver and Lungs of Mice with Sepsis: A Key Role for Adhesion Molecules on Vascular Endothelial Cells.","authors":"Zhu, Zhixing; Chambers, Stephen; Bhatia, Madhav","year":2024,"journal":"International journal of molecular sciences, 25(12)","doi":"10.3390/ijms25126500","pmid":"38928206","tags":["substance-P","neuropeptides","immune-function"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"Substance P promoted leukocyte infiltration into liver and lungs during acute pancreatitis in mice, revealing a neuropeptide-mediated mechanism for multi-organ damage.","whyItMatters":"Acute pancreatitis kills thousands annually from organ failure, and there is no specific treatment to prevent multi-organ damage. Identifying Substance P as a driver of distant organ injury reveals a druggable target — NK1R blockers like aprepitant are already available.","specificNumbers":"SP upregulated both ICAM1 and VCAM1 on vascular endothelial cells in the liver and lungs, promoting leukocyte infiltration.","methodology":"Mouse model of acute pancreatitis. Assessed Substance P levels, NK1R signaling, leukocyte infiltration in liver and lungs, organ damage markers, and inflammation.","limitations":"Mouse pancreatitis model may not fully replicate human disease severity. The contribution of Substance P relative to other inflammatory mediators is unclear. Clinical translation requires testing NK1R blockade in pancreatitis patients."},{"rthcId":"RPEP-09697","title":"Oral Delivery of Liraglutide-Loaded Zein/Eudragit-Chitosan Nanoparticles Provides Pharmacokinetic and Glycemic Outcomes Comparable to Its Subcutaneous Injection in Rats.","authors":"Ziebarth, Jeferson; da Silva, Letícia Marina; Lorenzett, Ariane Krause Padilha; Figueiredo, Ingrid Delbone; Carlstrom, Paulo Fernando; Cardoso, Felipe Nunes; de Freitas, André Luiz Ferreira; Baviera, Amanda Martins; Mainardes, Rubiana Mara","year":2024,"journal":"Pharmaceutics, 16(5)","doi":"10.3390/pharmaceutics16050634","pmid":"38794296","tags":["GLP-1-receptor-agonists","liraglutide","peptide-drug-delivery"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Zein/Eudragit-chitosan nanoparticles protected liraglutide from gastric degradation, provided sustained oral delivery, and achieved effective glycemic control in animal models.","whyItMatters":"Liraglutide injection is a barrier to patient adherence. An oral nanoparticle formulation could make this effective GLP-1 drug as easy as taking a pill, dramatically expanding its use.","specificNumbers":"Oral nanoparticle formulation achieved comparable pharmacokinetic and glycemic outcomes to subcutaneous injection in diabetic rats.","methodology":"Formulated liraglutide-loaded zein/Eudragit nanoparticles coated with chitosan. Characterized particle size, encapsulation, release kinetics, acid stability, and in vivo glycemic control.","limitations":"Animal study — human GI conditions and absorption may differ. Bioavailability compared to injection needs quantification. Manufacturing scalability and cost of nanoparticles need assessment."},{"rthcId":"RPEP-09698","title":"Visual stimulation and brain-derived neurotrophic factor (BDNF) have protective effects in experimental autoimmune uveoretinitis.","authors":"Zloh, Miloslav; Kutilek, Patrik; Hejda, Jan; Fiserova, Ivana; Kubovciak, Jan; Murakami, Masaaki; Stofkova, Andrea","year":2024,"journal":"Life sciences, 355, 122996","doi":"10.1016/j.lfs.2024.122996","pmid":"39173995","tags":["BDNF","neuropeptides","immune-function"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Visual stimulation increased retinal BDNF levels and provided neuroprotective effects against retinal cell degeneration.","whyItMatters":"Retinal degeneration causes irreversible blindness. A non-invasive, non-pharmacological approach to boosting neuroprotective BDNF could complement existing treatments and be accessible to anyone.","specificNumbers":"12 hours/day high-contrast visual stimulation from days 1-14 post-immunization reduced EAU clinical scores and inflammatory markers.","methodology":"Retinal degeneration model with visual stimulation intervention. Measured BDNF levels, retinal cell survival, and functional outcomes.","limitations":"The degree of protection may be modest compared to drug interventions. Optimal stimulation parameters need optimization. Long-term effects of chronic visual stimulation unknown."},{"rthcId":"RPEP-09699","title":"Ultrasound-Responsive HBD Peptide Hydrogel with Antibiofilm Capability for Fast Diabetic Wound Healing.","authors":"Zong, Lanlan; Teng, Runxin; Zhang, Huiqi; Liu, Wenshang; Feng, Yu; Lu, Zhengmao; Zhou, Yuxiao; Fan, Zhen; Li, Meng; Pu, Xiaohui","year":2024,"journal":"Advanced science (Weinheim, Baden-Wurttemberg, Germany), 11(42), e2406022","doi":"10.1002/advs.202406022","pmid":"39248340","tags":["bioactive-peptides","wound-healing","antimicrobial-peptides-defensins"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"Ultrasound-responsive HBD hydrogel achieved on-demand biofilm disruption and peptide release, clearing wound infections and accelerating tissue healing.","whyItMatters":"Biofilm-infected chronic wounds are extremely difficult to treat and cost billions in healthcare. A smart hydrogel that breaks biofilms and delivers antimicrobial peptides on demand could transform chronic wound management.","specificNumbers":"HBD peptide derived from von Willebrand Factor self-assembled into angiogenic nanoparticles with antibiofilm capability when activated by ultrasound.","methodology":"Developed ultrasound-responsive hydrogel with HBD peptide. Tested antibiofilm capability under ultrasound activation. Assessed wound healing in infected wound models.","limitations":"Preclinical wound study. Ultrasound equipment is needed at the wound site. Long-term HBD stability in the hydrogel needs evaluation."},{"rthcId":"RPEP-09700","title":"Angiotensin I and II Stimulate Cell Invasion of SARS-CoV-2: Potential Mechanism via Inhibition of ACE2 Arm of RAS.","authors":"Zorad, S; Skrabanova, M; Zilkova, M; Cente, M; Turic Csokova, N; Kovacech, B; Cizkova, D; Filipcik, P","year":2024,"journal":"Physiological research, 73(1), 27-35","doi":null,"pmid":"38466002","tags":["cardiovascular-health","immune-function"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Both angiotensin I and angiotensin II stimulated SARS-CoV-2 cell invasion, suggesting endogenous peptide hormones can facilitate viral entry via the ACE2 pathway.","whyItMatters":"Understanding why cardiovascular patients fare worse with COVID-19 has been a major question. This study shows that elevated angiotensin levels — common in hypertension — may directly help the virus enter cells.","specificNumbers":"Low and moderate concentrations of Ang I and Ang II stimulated pseudovirus entry into both HEK-ACE2 and Vero E6 cells.","methodology":"Cell-based viral invasion assays testing the effect of angiotensin I and II on SARS-CoV-2 entry. Assessed ACE2 pathway involvement and potential mechanisms.","limitations":"In vitro cell study. Angiotensin levels in patients are influenced by many factors. The clinical significance of this mechanism relative to other COVID risk factors is unclear."},{"rthcId":"RPEP-09701","title":"Interplay between cannabinoids and the neuroimmune system in migraine.","authors":"Zorrilla, Erik; Della Pietra, Adriana; Russo, Andrew F","year":2024,"journal":"The journal of headache and pain, 25(1), 178","doi":"10.1186/s10194-024-01883-3","pmid":"39407099","tags":["CGRP","Neuropeptides"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"The endocannabinoid system and CGRP signaling share neuroimmune pathways in migraine, with cannabinoids capable of modulating CGRP release and neuroinflammation.","whyItMatters":"Many migraine patients use cannabis alongside or instead of conventional medications. Understanding how cannabinoids affect CGRP — the key migraine peptide — is essential for informed treatment decisions and potential drug development.","specificNumbers":"No specific clinical trial numbers reported — this is a mechanistic review of preclinical and translational evidence.","methodology":"Narrative review of published literature on cannabinoid-CGRP interactions in migraine neurobiology.","limitations":"Narrative review. Most cannabinoid-CGRP interaction data is preclinical. Clinical evidence for cannabis in migraine is limited. Cannabis composition and dosing variability make research challenging."},{"rthcId":"RPEP-09702","title":"Anti-CGRP mAbs for the Preventive Treatment of Migraine: An Overview Review and a Cost Saving Analysis in the Global Scenario.","authors":"Zovi, Andrea; Lasala, Ruggero; Ferrara, Francesco; Langella, Roberto; Vitiello, Antonio; Sabbatucci, Michela; Musazzi, Umberto Maria","year":2024,"journal":"Hospital pharmacy, 59(2), 165-172","doi":"10.1177/00185787231196763","pmid":"38450361","tags":["CGRP","Neuropeptides"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"All four anti-CGRP mAbs are effective for migraine prevention with good safety profiles, and real-world data largely confirms clinical trial results with additional long-term insights.","whyItMatters":"With four CGRP antibodies available, patients and clinicians need comprehensive comparisons to make informed treatment choices. This review provides the most complete picture available.","specificNumbers":"No specific efficacy percentages reported in the available abstract. The study compared performance across different anti-CGRP monoclonal antibodies in the global market.","methodology":"Overview review synthesizing clinical trial data, systematic reviews, meta-analyses, and real-world evidence for erenumab, fremanezumab, galcanezumab, and eptinezumab.","limitations":"Overview review cannot replace systematic comparison with meta-analysis. Head-to-head trials between CGRP antibodies are limited. Real-world data has inherent selection and confounding biases."},{"rthcId":"RPEP-09703","title":"Intranasal administration of dextran-pramlintide polyelectrolyte complex-coated nanoemulsions improves cognitive impairments in a mouse model of Alzheimer's disease.","authors":"Zuglianello, Carine; França, Angela P; de Souza, Bruna S; Agnes, Jonathan P; Prediger, Rui D; Lemos-Senna, Elenara","year":2024,"journal":"International journal of biological macromolecules, 281(Pt 1), 136158","doi":"10.1016/j.ijbiomac.2024.136158","pmid":"39362444","tags":["Amylin analogues","Peptide delivery systems"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Dextran-pramlintide nanoparticles delivered via intranasal route achieved nose-to-brain pramlintide delivery, demonstrating a non-invasive peptide brain delivery approach.","whyItMatters":"Amylin and its analogs show promise for neurodegenerative diseases, but brain delivery is a major hurdle. Intranasal nanoparticles could make brain-targeted amylin therapy as simple as a nasal spray.","specificNumbers":"Specific dosing and cognitive test scores were not detailed in the available abstract portion.","methodology":"Formulated pramlintide in dextran polyelectrolyte complex-coated nanoparticles. Characterized particle properties, stability, and nasal permeation. Assessed nose-to-brain delivery.","limitations":"Preliminary delivery study. The amount of pramlintide reaching the brain via nasal route may be limited. Long-term safety of nasal nanoparticle administration needs evaluation."},{"rthcId":"RPEP-09704","title":"Pollen-Food Allergy Syndrome: From Food Avoidance to Deciphering the Potential Cross-Reactivity between Pru p 3 and Ole e 7.","authors":"Álvarez, Paula; Aguado, Rocío; Molina, Juan; Trujillo-Aguilera, Antonio; Villalba, Mayte; Díaz-Perales, Araceli; Oeo-Santos, Carmen; Chicano, Eduardo; Blanco, Nadine; Navas, Ana; Ruiz-León, Berta; Jurado, Aurora","year":2024,"journal":"Nutrients, 16(17)","doi":"10.3390/nu16172869","pmid":"39275185","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09705","title":"In vitro cellular uptake and insulin secretion studies on INS-1E cells of exendin-4-loaded self-nanoemulsifying drug delivery systems.","authors":"Çelik Tekeli, Merve; Yalçın, Yaprak; Verdi, Hasibe; Aktaş, Yeşim; Çelebi, Nevin","year":2024,"journal":"Pharmaceutical development and technology, 29(10), 1101-1110","doi":"10.1080/10837450.2024.2423823","pmid":"39474799","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Exendin-4 loaded in SNEDDS and exendin-4/chymostatin SNEDDS (with an enzyme inhibitor for additional protection) were tested on INS-1E rat pancreatic beta cells:\n\n- At low glucose (2.8 mM): Ex-4 SNEDDS increased insulin levels 2.21-fold and ex-4/chym SNEDDS increased them 2.17-fold compared to control\n- At high glucose (16.7 mM): Both formulations also increased insulin levels compared to control\n- Cell viability increased at higher dilution ratios, indicating safety at appropriate concentrations\n- Cellular uptake studies showed SNEDDS delivered cargo to cell nuclei (visualized with coumarin-6), while free solution only reached the cell cytoplasm — demonstrating superior intracellular delivery","whyItMatters":"Converting injectable peptide drugs to oral forms remains a major pharmaceutical challenge. Exendin-4 (marketed as exenatide/Byetta) must be injected twice daily, limiting patient compliance. SNEDDS offer several practical advantages: they protect peptides from stomach acid and enzymes, are simple to manufacture at scale, and reduce food-related absorption variability. The demonstration of enhanced intracellular delivery (reaching the nucleus vs. just the cytoplasm) is particularly significant and could improve the biological effectiveness of orally delivered peptides.","specificNumbers":"","methodology":"Researchers formulated exendin-4 and exendin-4/chymostatin in self-nanoemulsifying drug delivery systems. Cytotoxicity was assessed via cell viability assays on INS-1E rat pancreatic beta cells at various dilution ratios. Insulin secretion was measured after incubating cells with the formulations at low (2.8 mM) and high (16.7 mM) glucose concentrations. Cellular uptake was visualized using fluorescent coumarin-6-loaded SNEDDS and confocal microscopy, comparing intracellular distribution of SNEDDS-delivered versus free coumarin-6.","limitations":"All experiments were conducted in vitro using a rat beta cell line (INS-1E), which may not represent human pancreatic beta cell behavior. No in vivo oral bioavailability data was generated — the critical test of whether SNEDDS can deliver exendin-4 through the actual gut environment. The chymostatin enzyme inhibitor adds complexity and potential safety concerns for human use. Specific insulin secretion values at high glucose concentrations were not clearly stated in the abstract. Long-term stability of the exendin-4 SNEDDS formulation was not characterized."},{"rthcId":"RPEP-09706","title":"Revolutionizing migraine management: advances and challenges in CGRP-targeted therapies and their clinical implications.","authors":"Özge, A; Baykan, B; Bıçakçı, Ş; Ertaş, M; Atalar, A Ç; Gümrü, S; Karlı, N","year":2024,"journal":"Frontiers in neurology, 15, 1402569","doi":"10.3389/fneur.2024.1402569","pmid":"38938785","tags":[],"studyType":"review","evidenceStrength":"moderate","keyFinding":"This comprehensive review examines the paradigm shift in migraine treatment driven by therapies targeting calcitonin gene-related peptide (CGRP) — a neuropeptide central to migraine pathophysiology. CGRP monoclonal antibodies (for prevention) and gepants (small molecule CGRP receptor antagonists, for both acute and preventive use) have demonstrated strong efficacy and tolerability in clinical trials. The review highlights that despite these advances, significant barriers persist: misdiagnosis, medication overuse headaches, high costs, limited long-term safety data, and restricted access to specialist care, particularly in developing countries like Turkiye.","whyItMatters":"Migraine affects 14.1% of the world's population and has historically been undertreated and misunderstood. For decades, migraine treatments were borrowed from other conditions — blood pressure drugs, antidepressants, anti-seizure medications. CGRP-targeted therapies represent the first class of treatments designed specifically for migraine based on its underlying biology. This review contextualizes how these peptide-based treatments have transformed the field while honestly addressing the barriers to global access.","specificNumbers":"14.1% global prevalence of migraine","methodology":"This is a narrative review examining migraine pathophysiology, the role of CGRP in trigeminovascular activation, clinical trial data for CGRP monoclonal antibodies and gepants, pharmacokinetic and pharmacodynamic profiles, safety and tolerability data, and real-world treatment barriers. The authors provide strategic recommendations for improving migraine care, with particular focus on Turkiye and developing nations.","limitations":"As a narrative review, this article does not employ systematic review methodology or meta-analysis. The strategic recommendations are specifically tailored to Turkiye and developing countries, which may limit direct applicability to other healthcare systems. The review acknowledges the limited availability of long-term efficacy data for CGRP-targeted therapies."},{"rthcId":"RPEP-09707","title":"A case control study investigating the methylation levels of GHRL and GHSR genes in alcohol use disorder.","authors":"Özkan-Kotiloğlu, Selin; Kaya-Akyüzlü, Dilek; Güven, Emine; Doğan, Özlem; Ağtaş-Ertan, Ece; Özgür-İlhan, İnci","year":2024,"journal":"Molecular biology reports, 51(1), 663","doi":"10.1007/s11033-024-09585-4","pmid":"38771494","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09708","title":"Antimicrobial Peptides and Their Anti-Leishmanial Efficacies on Leishmania tropica Promastigotes In vitro.","authors":"Ünübol, Nihan; Çavuş, İbrahim; Polat, Tuba; Kurt, Özgür; Özbilgin, Ahmet; Kocagöz, Tanıl","year":2024,"journal":"Turkiye parazitolojii dergisi, 48(3), 135-141","doi":"10.4274/tpd.galenos.2024.48658","pmid":"39373586","tags":["antimicrobial-peptides","cathelicidins"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Rationally designed cathelicidin-like helical peptides demonstrated superior anti-leishmanial activity against L. tropica promastigotes compared to natural cathelicidin peptides in vitro.","whyItMatters":"Leishmaniasis affects millions worldwide, and first-line drugs are losing effectiveness due to resistance. Antimicrobial peptides offer a fundamentally different killing mechanism — membrane disruption — that's much harder for parasites to evolve resistance against.","specificNumbers":"Cathelicidin AMPs tested against L. tropica promastigotes (specific concentrations and kill rates not detailed in abstract excerpt).","methodology":"In vitro study designing cathelicidin-like helical peptides (CLHPs) and testing their efficacy against Leishmania tropica promastigotes, with comparison to natural cathelicidin antimicrobial peptides.","limitations":"In vitro study only — no animal model testing. Only tested against promastigote form (the extracellular stage), not the clinically relevant intracellular amastigote form. Cytotoxicity to human cells not fully characterized. Scale-up and delivery challenges not addressed."},{"rthcId":"RPEP-09709","title":"Human β-defensin 2: a connection between infections and allergic skin diseases.","authors":"Štrajtenberger, Maja; Stipić-Marković, Asja; Barac, Ema; Artuković, Marinko; Lugović-Mihić, Liborija","year":2024,"journal":"Acta dermatovenerologica Alpina, Pannonica, et Adriatica, 33(3), 135-139","doi":null,"pmid":"39324351","tags":["defensins","antimicrobial-peptides","immune-system","skin-health"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"HBD2 promotes mast cell activation and degranulation, linking antimicrobial defense to allergic reactions. Elevated serum HBD2 found in atopic dermatitis, psoriasis, and chronic spontaneous urticaria. CSU patients with angioedema have higher HBD2 than those without. HBD2 is produced by keratinocytes, epithelial cells, and macrophages in response to microorganisms or pro-inflammatory cytokines.","whyItMatters":"Understanding how antimicrobial peptides like HBD2 trigger allergic responses explains why skin infections often worsen allergic diseases. This dual-function concept could lead to new therapeutic strategies — either dampening HBD2's allergic effects while preserving antimicrobial function, or using HBD2 levels as a biomarker to guide treatment decisions in skin diseases.","specificNumbers":"HBD-2 is produced by epithelial cells, keratinocytes, and macrophages in response to microbial exposure or pro-inflammatory cytokines.","methodology":"Narrative review of published literature on human β-defensin 2 in dermatological and allergic conditions, covering its production, antimicrobial functions, role in mast cell activation, and clinical associations with skin diseases.","limitations":"Narrative review without systematic methodology. Limited data on HBD2 skin expression levels in allergic diseases (most studies measure serum levels). The causal relationship between elevated HBD2 and allergic disease is not established — HBD2 elevation could be a consequence rather than a cause. Published in a regional dermatology journal with potentially limited peer review scope."},{"rthcId":"RPEP-09710","title":"Pharmacological Treatment of Obesity in Older Adults.","authors":"Žižka, Ondřej; Haluzík, Martin; Jude, Edward B","year":2024,"journal":"Drugs & aging, 41(11), 881-896","doi":"10.1007/s40266-024-01150-9","pmid":"39514148","tags":["GLP-1-receptor-agonists","weight-management","anti-aging"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"GLP-1 drugs are effective for weight management in older adults but require careful monitoring for sarcopenia and bone loss, with exercise and nutrition strategies to mitigate risks.","whyItMatters":"Older adults are the fastest-growing demographic taking GLP-1 drugs. Understanding how to maximize weight-loss benefits while protecting muscle and bone health is critical for safe prescribing in this population.","specificNumbers":"Review covers obesity in adults aged 65 and older, examining effects on comorbidities, quality of life, and life expectancy.","methodology":"Narrative review of pharmacological obesity treatment in older adult populations, focusing on GLP-1 receptor agonists.","limitations":"Narrative review. Clinical trial data in older adults may be limited as many trials have age restrictions. Individual variability in aging is high."},{"rthcId":"RPEP-09711","title":"Barr 2025 Orexin Antagonism Opioid Use Disorder","authors":"","year":2025,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09712","title":"Carvas 2025 Cagrilintide Lowers Bodyweight Through","authors":"","year":2025,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09713","title":"Chen 2025 Ai Optimized Pdc Linkers","authors":"","year":2025,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09714","title":"Chen 2025 Peptide Therapeutics Alzheimers Delivery","authors":"","year":2025,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09715","title":"Cummings 2025 Alzheimers Pipeline Review","authors":"","year":2025,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09716","title":"Fda Orphan Drug Designation","authors":"","year":2025,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09717","title":"Fda Rdea Rare Disease Guidance","authors":"","year":2025,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09718","title":"Gupta 2025 Long Covid Viral Persistence Review","authors":"","year":2025,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09719","title":"Gupta 2025 Mechanistic Insights Long Covid","authors":"","year":2025,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09720","title":"Lian 2025 Convergence Of Plasmiddriven Virulence","authors":"","year":2025,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09721","title":"Movahednasab 2025 Glp1based Therapies For Type","authors":"","year":2025,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09722","title":"Paoletti 2025 Pharmacokinetic Considerations For Gonadotropi","authors":"","year":2025,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09723","title":"Peptide Rare Disease Fda Approvals","authors":"","year":2025,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09724","title":"Recover 2025 Long Covid Proinflammatory Exhaustion","authors":"","year":2025,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09725","title":"Wang 2025 A Novel Antimicrobial Peptide","authors":"","year":2025,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09726","title":"Comparative Efficacy of Tirzepatide vs. Semaglutide in Reducing Body Weight in Humans: A Systematic Review and Meta-Analysis of Clinical Trials and Real-World Data.","authors":"Aamir, Ahmad Bin; Latif, Rabia; Alqoofi, Jood Faisal; Almarzoq, Fatimah Abdulkarim; Fallatah, Joory Osamah; Hassan, Ghala Abdullah; Saab, Fatimah Abbas Abdullah Al Abu","year":2025,"journal":"Journal of clinical medicine research, 17(5), 285-296","doi":"10.14740/jocmr6231","pmid":"40503067","tags":["Tirzepatide","Semaglutide","GLP-1 receptor agonists","GIP analogues"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Tirzepatide produced significantly greater body weight reduction than semaglutide in both clinical trial and real-world data, confirming the superior efficacy of dual GLP-1/GIP agonism for weight loss.","whyItMatters":"Patients and clinicians need direct comparisons to make informed treatment choices. This comprehensive analysis provides the strongest evidence yet that tirzepatide outperforms semaglutide for weight loss.","specificNumbers":"751 studies were initially identified, then filtered by eligibility criteria. Specific weight loss differences between the drugs were analyzed but exact numbers were not provided in the available abstract.","methodology":"Systematic review and meta-analysis of clinical trials and real-world studies comparing tirzepatide and semaglutide for body weight reduction. Published in 2025.","limitations":"Indirect comparisons dominate — few true head-to-head RCTs exist. Real-world data has confounding factors. Different doses of each drug were compared across studies. Patient populations may differ between tirzepatide and semaglutide studies."},{"rthcId":"RPEP-09727","title":"The Effect of Semaglutide and GLP-1 RAs on Risk of Nonarteritic Anterior Ischemic Optic Neuropathy.","authors":"Abbass, Nadia J; Nahlawi, Raya; Shaia, Jacqueline K; Allan, Kevin C; Kaelber, David C; Talcott, Katherine E; Singh, Rishi P","year":2025,"journal":"American journal of ophthalmology, 274, 24-31","doi":"10.1016/j.ajo.2025.02.025","pmid":"40015592","tags":["GLP-1 receptor agonists","Semaglutide"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Study evaluated the association between semaglutide/GLP-1 RA use and NAION risk using large-scale clinical data, addressing a flagged safety signal for this rare eye condition.","whyItMatters":"NAION can cause permanent vision loss. With millions taking GLP-1 drugs, even a small increase in NAION risk would affect thousands of people. Clarifying this safety signal is critical.","specificNumbers":"Patients aged 12 and older were included. The study used the TriNetX network, which covers millions of U.S. health records. Exact event rates not detailed in available abstract.","methodology":"Large-scale analysis of clinical data examining the association between GLP-1 receptor agonist use and NAION incidence in patients with T2DM and/or obesity.","limitations":"NAION is extremely rare, limiting statistical power even in large datasets. Diabetes and obesity themselves are NAION risk factors, confounding the analysis. Observational data cannot prove causation."},{"rthcId":"RPEP-09728","title":"Glucagon-like peptide-1 receptor analogues and beyond: emerging obesity pharmacotherapies.","authors":"Abburi, Kaivalya; Melson, Eka; Miras, Alexander D; Papamargaritis, Dimitris","year":2025,"journal":"Panminerva medica, 67(3), 138-154","doi":"10.23736/S0031-0808.25.05339-X","pmid":"40728225","tags":["GLP-1 receptor agonists","Semaglutide","Tirzepatide"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"The obesity drug pipeline has expanded beyond single GLP-1 agonists to include dual agonists, triple agonists, and amylin combinations that promise 20-25%+ weight loss.","whyItMatters":"Current GLP-1 drugs achieve ~15-17% weight loss. Next-generation peptide drugs targeting multiple receptors could achieve 25%+ weight loss — approaching bariatric surgery results without surgery.","specificNumbers":"Bariatric surgery achieves about 20–30% sustained weight loss. Specific drug weight loss percentages are covered in the full review.","methodology":"Narrative review of emerging obesity pharmacotherapies with focus on peptide-based dual and triple receptor agonists and combination strategies.","limitations":"Many drugs reviewed are still in clinical trials. Long-term safety data is limited for newer agents. Greater weight loss may come with increased side effects. Cost and access remain major barriers."},{"rthcId":"RPEP-09729","title":"Interest in Treatment with GLP-1 Receptor Agonists for the Management of Insufficient Weight Loss or Weight Regain After Bariatric Surgery.","authors":"Abdallah, Hussein; Klink, Wissam Hadi; Derienne, Joseph; Voican, Cosmin; Perlemuter, Gabriel; Courie, Rodi; Dagher, Ibrahim; Tranchart, Hadrien","year":2025,"journal":"Obesity surgery, 35(10), 4286-4291","doi":"10.1007/s11695-025-08210-y","pmid":"40913138","tags":["GLP-1 receptor agonists"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"GLP-1 receptor agonists consistently produce meaningful additional weight loss in bariatric surgery patients with insufficient weight loss or weight regain.","whyItMatters":"Bariatric surgery failure or weight regain affects hundreds of thousands of patients with limited treatment options. GLP-1 drugs offer a non-surgical rescue strategy.","specificNumbers":"100 patients were included, with 96 having undergone sleeve gastrectomy. Specific weight loss data from GLP-1 treatment was analyzed but not detailed in available abstract.","methodology":"Review of clinical studies examining GLP-1 RA use in post-bariatric surgery patients with insufficient weight loss or weight regain.","limitations":"Most studies are observational or small trials. Optimal timing, dose, and duration of GLP-1 therapy after surgery are not established. Insurance coverage for GLP-1 drugs post-surgery varies."},{"rthcId":"RPEP-09730","title":"Omarigliptin/shikonin combination alleviates cyclosporine-induced nephrotoxicity: The role of sirtuin 1, glucagon-like peptide-1, HMGB1/RAGE/TLR4 signaling, and p38/ERK/JNK MAPKs.","authors":"Abdallah, Marwa H; Atia, Hanan Abdelmawgoud; Elariny, Hemat A; Khalifa, Amany M; Saleh, Asmaa; Kabel, Ahmed M","year":2025,"journal":"Human & experimental toxicology, 44, 9603271251394693","doi":"10.1177/09603271251394693","pmid":"41172611","tags":["DPP-4 inhibitors","GLP-1 receptor agonists"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Omarigliptin/shikonin combination protected against cyclosporine nephrotoxicity by preserving GLP-1 signaling, reducing inflammation, and mitigating oxidative stress in kidney tissue.","whyItMatters":"Cyclosporine kidney damage limits its long-term use in transplant patients. If DPP-4 inhibitors can protect kidneys through GLP-1 preservation, transplant patients could use cyclosporine more safely for longer.","specificNumbers":"Specific dose levels and kidney function measurements were analyzed but not detailed in the available abstract.","methodology":"Animal study testing omarigliptin (DPP-4 inhibitor) and shikonin combination in cyclosporine-induced nephrotoxicity model. Assessed kidney function, GLP-1 levels, inflammatory markers, and oxidative stress.","limitations":"Animal study. Combination therapy adds complexity. The specific contributions of omarigliptin vs shikonin need dissection. Human translation requires clinical trials in transplant patients."},{"rthcId":"RPEP-09731","title":"Scorpion venom as a natural peptide source for innovative therapeutic solutions: A comprehensive review of its potential in emerging medical frontiers.","authors":"Abdallnasser Amen, Radwa; Atef Essmat, Rawan; Farid, Alyaa; Abdel-Rahman, Mohamed A; El-Sherif, Ahmed A; Zhang, Yonghong","year":2025,"journal":"Toxicon : official journal of the International Society on Toxinology, 268, 108603","doi":"10.1016/j.toxicon.2025.108603","pmid":"41033582","tags":["Antimicrobial peptides","Peptide drug development"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Scorpion venom contains diverse bioactive peptides with anticancer, antimicrobial, analgesic, and anti-inflammatory properties, with several candidates advancing toward clinical development.","whyItMatters":"Nature has spent millions of years optimizing venom peptides to affect biological targets. Harnessing these natural molecules could provide entirely new classes of drugs for cancer, infections, and pain — conditions where current treatments fall short.","specificNumbers":"No specific clinical trial numbers — this is a review of the breadth of therapeutic applications across the field.","methodology":"Comprehensive review of scorpion venom peptide characterization, mechanisms of action, and therapeutic applications across multiple disease areas.","limitations":"Most scorpion venom peptides are in early development. Venom peptides may have toxicity issues. Manufacturing synthetic versions at scale is challenging. Moving from venom characterization to clinical drugs takes years."},{"rthcId":"RPEP-09732","title":"Liraglutide orchestrates ferroptosis defense against murine cisplatin acute kidney injury: NRF2 activation via both KEAP1-dependent and -independent mechanisms is essential for SLC7A11/GPX4 renoprotection.","authors":"Abdel Razek, Nermeen S; Nassar, Noha N; Sayed, Rabab H; El-Sahar, Ayman E; Abdallah, Dalaal M","year":2025,"journal":"Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS), 92, 127755","doi":"10.1016/j.jtemb.2025.127755","pmid":"40972223","tags":["Liraglutide","GLP-1 receptor agonists"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Liraglutide protected against cisplatin-induced acute kidney injury by orchestrating ferroptosis defense, including enhanced antioxidant defenses and reduced iron accumulation.","whyItMatters":"Cisplatin kidney damage limits cancer treatment. If liraglutide can protect kidneys during chemotherapy, cancer patients on GLP-1 drugs for diabetes or obesity may have a built-in advantage, and liraglutide could be specifically added as a kidney protector during chemo.","specificNumbers":"Specific dose and kidney function measurements were analyzed but not detailed in available abstract.","methodology":"Mouse model of cisplatin-induced acute kidney injury treated with liraglutide. Assessed kidney function, ferroptosis markers (iron, lipid peroxidation, GPX4), antioxidant defenses, and kidney histology.","limitations":"Mouse study. Cisplatin doses in mice may not match human chemotherapy protocols. The interaction between liraglutide and cisplatin anticancer efficacy needs evaluation — kidney protection must not compromise cancer treatment."},{"rthcId":"RPEP-09733","title":"Neuroprotective Effects of Liraglutide and/or Rivastigmine Combination on the Rat Hippocampus.","authors":"Abdel-Aal, Raafat A; Hareedy, Mohammad Salem; Badary, Dalia M; Abdelnabi, Sara; Hussein, Abeer M R","year":2025,"journal":"Drug development research, 86(7), e70160","doi":"10.1002/ddr.70160","pmid":"41000001","tags":["Liraglutide","GLP-1 receptor agonists"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Liraglutide and rivastigmine combination provided enhanced neuroprotection compared to either drug alone in a rat neurodegeneration model.","whyItMatters":"Alzheimer's treatments have limited efficacy. Combining a GLP-1 drug with existing Alzheimer's medication could provide synergistic brain protection that neither achieves alone.","specificNumbers":"Liraglutide was given at 300 µg/kg daily and rivastigmine at 1 mg/kg daily, each for 6 weeks. AlCl₃ was given at 75 mg/kg for 60 days to induce the disease model.","methodology":"Rat model of neurodegeneration treated with liraglutide, rivastigmine, or combination. Assessed cognitive function, brain damage markers, and neuroprotective outcomes.","limitations":"Rat study. Human Alzheimer's is more complex than animal models. Optimal dosing of the combination needs determination. Drug interactions need safety evaluation."},{"rthcId":"RPEP-09734","title":"Unraveling the impact of semaglutide in a diabetic rat model of testicular dysfunction: Insights into spermatogenesis pathways and miRNA-148a-5p.","authors":"Abdel-Wahab, Basel A; El-Shoura, Ehab A M; Habeeb, Mohammed S; Aldabaan, Nayef A; Ahmed, Yasmine H; Zaafar, Dalia","year":2025,"journal":"Steroids, 213, 109537","doi":"10.1016/j.steroids.2024.109537","pmid":"39551458","tags":["Semaglutide","GLP-1 receptor agonists"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Semaglutide improved sperm parameters, reproductive hormones, and testicular histology in diabetic rats by reducing oxidative stress and inflammation.","whyItMatters":"Diabetes-related male infertility affects millions. If GLP-1 drugs protect testicular function alongside metabolic benefits, diabetic men on these drugs may preserve fertility better.","specificNumbers":"28 adult male rats were divided into 4 groups (7 per group). Specific testicular function measurements were analyzed but not detailed in the available abstract.","methodology":"Diabetic rat model treated with semaglutide. Assessed sperm count, motility, morphology, reproductive hormones, testicular histology, oxidative stress, and inflammatory markers.","limitations":"Rat study. Human male reproductive responses to GLP-1 drugs may differ. Effects of weight loss vs direct GLP-1R activation on testes are not separated."},{"rthcId":"RPEP-09735","title":"Ameliorative effect of GLP1 agonist on vascular calcification in normoglycemic aged rat aorta via miR34a/SIRT6/NRF2/HO-1 signalling pathway.","authors":"Abdelfattah, Amira Mohammed; Abdelnour, Hanim M; Askar, Eman M; Abdelhamid, Amira Mohamed; Elgarhi, Reham I","year":2025,"journal":"European journal of pharmacology, 1001, 177741","doi":"10.1016/j.ejphar.2025.177741","pmid":"40383222","tags":["Liraglutide","GLP-1 receptor agonists"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Liraglutide ameliorated vascular calcification in both normoglycemic and diabetic rat models, demonstrating direct vascular protection independent of glycemic control.","whyItMatters":"Vascular calcification has no treatment. Showing that liraglutide directly protects blood vessels — even without diabetes — suggests GLP-1 drugs could be used to treat or prevent vascular calcification in any patient.","specificNumbers":"Young rats were 3–4 months old, compared to aged rats. Specific calcification measurements and pathway expression levels were analyzed but not fully detailed in the available abstract.","methodology":"Vascular calcification models in both normoglycemic and diabetic rats. Treated with liraglutide. Assessed vascular calcium content, vessel function, and calcification markers.","limitations":"Rat model. Human vascular calcification involves different pathologies (atherosclerotic vs medial). Optimal dosing for anti-calcification effect not established."},{"rthcId":"RPEP-09736","title":"Unveiling the Therapeutic Potential of Dulaglutide in Mitigating Tacrolimus-Induced Nephrotoxicity Through Targeting the miR-22/HMGB-1/TLR4/MyD88/NF-κB Trajectory.","authors":"Abdelhady, Rasha; Arab, Hany H; Fakhr Eldeen, Rasha R; Shalaby, Heba Nasr; Nawwar, Dalia A; Elhemely, Mai Abdallah; Sayed, Rabab H","year":2025,"journal":"Archiv der Pharmazie, 358(4), e3127","doi":"10.1002/ardp.202500023","pmid":"40205909","tags":["Dulaglutide","GLP-1 receptor agonists"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Dulaglutide mitigated tacrolimus-induced nephrotoxicity by reducing inflammation, oxidative stress, and fibrosis, supporting GLP-1R activation as a renoprotective strategy during immunosuppression.","whyItMatters":"Chronic kidney damage limits how long transplant patients can use immunosuppressants. GLP-1 kidney protection could extend transplant organ survival by allowing safer long-term immunosuppression.","specificNumbers":"Specific dosing and kidney function markers were analyzed but not fully detailed in the available abstract.","methodology":"Animal model of tacrolimus-induced nephrotoxicity treated with dulaglutide. Assessed kidney function, histology, inflammatory markers, oxidative stress, and fibrosis.","limitations":"Animal study. Interaction between dulaglutide and tacrolimus immunosuppressive efficacy needs evaluation. Transplant patient populations may have additional complicating factors."},{"rthcId":"RPEP-09737","title":"Glucagon-like Peptide-1 Receptor Agonists in Heart Failure: Mechanisms, Evidence and Identifying Optimal Candidates.","authors":"Abdelhamid, Magdy; Abdrabou, Mostafa M; Faris, Emanuel; El Kafas, Sameh; Hosny, Mohamed; Hassan, Ahmed","year":2025,"journal":"Cardiac failure review, 11, e28","doi":"10.15420/cfr.2025.17","pmid":"41234532","tags":["GLP-1 receptor agonists"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"GLP-1 drugs benefit heart failure through multiple mechanisms: direct cardiac protection, anti-inflammation, improved cardiac metabolism, weight loss, and vascular function improvement.","whyItMatters":"Heart failure is a leading cause of hospitalization and death. GLP-1 drugs are proving to be among the most important new heart failure treatments, especially for the common but hard-to-treat HFpEF subtype.","specificNumbers":"Specific trial results are discussed in the full review. Cardiovascular outcome trials initially showed positive signals for heart benefits.","methodology":"Review of mechanisms and clinical evidence for GLP-1 receptor agonists in heart failure management.","limitations":"Some mechanistic evidence is preclinical. Heart failure subtypes may respond differently to GLP-1 drugs. The relative contribution of weight loss vs direct cardiac effects is debated."},{"rthcId":"RPEP-09738","title":"Harnessing GLP-1 Receptor Agonists for Obesity Treatment: Prospects and Obstacles on the Horizon.","authors":"Abdelrahman, Riad Mohammed; Musa, Taha Hussein; Arbab, Ismail Adam; Suliman, Mohsen Hussein; Ahmed, Eltieb Omer; Mohamed, Asma Noureldaim; Musa, Hassan Hussein; Jalal, Mohammed; Gasmallah, Sahar Ibrahim","year":2025,"journal":"Journal of obesity, 2025, 9919810","doi":"10.1155/jobe/9919810","pmid":"41333115","tags":["GLP-1 receptor agonists","Semaglutide","Liraglutide","Tirzepatide"],"studyType":"review","evidenceStrength":"strong","keyFinding":"GLP-1 drugs are highly effective for obesity but face challenges including weight regain on discontinuation, cost barriers, GI side effects, and counterfeit drug risks.","whyItMatters":"GLP-1 drugs could help the 650+ million people with obesity worldwide, but only if the barriers of cost, access, tolerability, and long-term treatment sustainability are addressed.","specificNumbers":"Three FDA-approved GLP-1 drugs for obesity: liraglutide, semaglutide, and tirzepatide. Additional agents are used off-label.","methodology":"Comprehensive review of GLP-1 RA obesity treatment evidence, emerging agents, and current obstacles to widespread implementation.","limitations":"Review reflects a rapidly evolving landscape — new drugs and pricing changes may alter conclusions. Different healthcare systems face different access challenges. Long-term safety data continues to accumulate."},{"rthcId":"RPEP-09739","title":"Tirzepatide associated autoimmune encephalitis: A case report.","authors":"Abdi, Asad; Ariaei, Armin; Hemasian, Helia; Shahabi, Shahab; Sina, Farzad","year":2025,"journal":"Journal of the American Pharmacists Association : JAPhA, 65(5), 102474","doi":"10.1016/j.japh.2025.102474","pmid":"40609684","tags":["Tirzepatide","GLP-1 receptor agonists"],"studyType":"case series","evidenceStrength":"preliminary","keyFinding":"Case report of autoimmune encephalitis temporally associated with tirzepatide use — one of the first reported serious neurological autoimmune events linked to GLP-1/GIP agonism.","whyItMatters":"As tirzepatide is prescribed to millions, even rare but serious adverse events become important. Autoimmune encephalitis is treatable if caught early, so awareness of this potential association is critical.","specificNumbers":"One 18-year-old patient. No prior risk factors for autoimmune conditions.","methodology":"Single case report documenting clinical presentation, diagnostic workup, temporal association with tirzepatide, treatment, and outcome.","limitations":"Single case report — the weakest form of evidence. Temporal association does not prove causation. The patient may have had predisposing autoimmune factors. Autoimmune encephalitis can occur without drug triggers."},{"rthcId":"RPEP-09740","title":"Efficacy and safety of retatrutide, a novel GLP-1, GIP, and glucagon receptor agonist for obesity treatment: a systematic review and meta-analysis of randomized controlled trials.","authors":"Abdrabou Abouelmagd, Alaa; Abdelrehim, Amro Mamdouh; Bashir, Mohamed Nabih; Abdelsalam, Fares; Marey, Ahmed; Tanas, Yousef; Abuklish, Duha Milad; Belal, Mohamed Mohamed","year":2025,"journal":"Proceedings (Baylor University. Medical Center), 38(3), 291-303","doi":"10.1080/08998280.2025.2456441","pmid":"40291085","tags":["GLP-1 receptor agonists","GIP analogues","Glucagon"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Retatrutide achieved up to ~24% weight loss as a triple GLP-1/GIP/glucagon agonist, with acceptable safety and metabolic benefits beyond what dual agonists provide.","whyItMatters":"24% weight loss approaches bariatric surgery results without surgery. If retatrutide proves safe in larger trials, it could become the most effective non-surgical obesity treatment ever developed.","specificNumbers":"Databases searched through May 2024. Specific weight loss percentages and number of included trials were analyzed but not detailed in available abstract.","methodology":"Review of retatrutide clinical trial data, triple receptor mechanism, efficacy and safety outcomes.","limitations":"Phase 2 data showed the 24% weight loss; phase 3 results still pending. GI side effects may be more common with triple agonism. Glucagon activation raises theoretical concerns about blood sugar in some patients. Long-term safety unknown."},{"rthcId":"RPEP-09741","title":"Glycemic and non-glycemic benefits of initial triple therapy versus sequential add-on therapy in patients with new-onset diabetes: results from the EDICT study.","authors":"Abdul-Ghani, Muhammad; Puckett, Curtiss; Abdelgani, Siham; Merovci, Aurora; Lavrynenko, Olga; Adams, John; Triplitt, Curtis; DeFronzo, Ralph A","year":2025,"journal":"BMJ open diabetes research & care, 13(2)","doi":"10.1136/bmjdrc-2025-004981","pmid":"40288809","tags":["Exenatide","GLP-1 receptor agonists"],"studyType":"RCT","evidenceStrength":"moderate","keyFinding":"Initial triple therapy including exenatide provided superior glycemic control and non-glycemic benefits (weight, blood pressure) compared to sequential add-on therapy in type 2 diabetes.","whyItMatters":"Delaying effective treatment allows diabetes to progressively damage beta cells. Starting with triple therapy including a GLP-1 drug may preserve beta cell function and achieve better long-term outcomes.","specificNumbers":"29 patients received initial triple therapy. Both groups maintained good blood sugar control for 6 years. Specific cIMT and liver fat measurements were compared.","methodology":"Comparative study of initial triple therapy (including exenatide) versus sequential add-on in patients with type 2 diabetes. Assessed HbA1c, body weight, blood pressure, and metabolic parameters.","limitations":"Study design and duration vary. Triple therapy is more complex and expensive. Patient adherence to three drugs from the start may be challenging. Long-term outcomes need confirmation."},{"rthcId":"RPEP-09742","title":"Effects of Ghrelin Hormone on Alzheimer's and Parkinson's Disease: A Systematic Review of the Existing Literature.","authors":"Abdulazeez, Yousif; Utami, Rifka Nurul; Al-Jamal, Khuloud T; Mok, Zi Hong","year":2025,"journal":"ACS chemical neuroscience, 16(21), 4159-4171","doi":"10.1021/acschemneuro.5c00683","pmid":"41128636","tags":["Ghrelin & growth hormone secretagogues","Neuropeptides"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Ghrelin consistently showed neuroprotective effects in AD and PD studies: reduced neuroinflammation, oxidative stress, and pathological protein aggregation, with improved cognitive and motor outcomes.","whyItMatters":"Neurodegenerative diseases have limited treatments. Ghrelin is a natural peptide with multi-target neuroprotective effects that could be developed into a new therapeutic approach for AD and PD.","specificNumbers":"The review distinguishes between acylated ghrelin (AG), which activates brain receptors, and unacylated ghrelin (UAG), which does not have these brain effects.","methodology":"Systematic review of published studies on ghrelin's effects in Alzheimer's and Parkinson's disease, covering preclinical and clinical evidence.","limitations":"Most evidence is preclinical. Clinical data is limited. Ghrelin has effects on appetite and growth hormone that may cause unwanted side effects. Optimal dosing for neuroprotection is unknown."},{"rthcId":"RPEP-09743","title":"Safety and Efficacy of Semaglutide in Patients With Chronic Kidney Disease, With or Without Type 2 Diabetes: A Systematic Review and Meta-Analysis.","authors":"Abdullah, Ali; Sagreeka, F N U; Aniket, Gurdas Alias; Lal, Rohan; Geeta, F N U; Bai, Anusha; Ahmed, Ghazi Uddin; Raza, Ahmed Asad; Shaikh, Varisha Fatima; Sanaullah, Owais; Sabahat, Syeda Elezeh; Ghori, Ahzam Khan; Bhutto, Seema Habib; Tesfaye, Mahir","year":2025,"journal":"Endocrinology, diabetes & metabolism, 8(6), e70136","doi":"10.1002/edm2.70136","pmid":"41276951","tags":["Semaglutide","GLP-1 receptor agonists"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Semaglutide demonstrated safety and efficacy in CKD patients with and without diabetes, showing metabolic benefits and kidney-protective effects in this high-risk population.","whyItMatters":"CKD patients have the highest cardiovascular risk and limited treatment options. Confirming semaglutide is safe and beneficial in CKD expands its use to a population that needs it most.","specificNumbers":"Over 500 million people globally have chronic kidney disease. This meta-analysis included both diabetic and non-diabetic CKD populations.","methodology":"Analysis of semaglutide safety and efficacy data in patients with chronic kidney disease, comparing outcomes in diabetic and non-diabetic CKD populations.","limitations":"Analysis details not fully available from abstract. CKD severity stages and specific kidney outcomes need examination. Drug dosing may need adjustment in severe CKD."},{"rthcId":"RPEP-09744","title":"Structures, Interactions, and Antimicrobial Activity of the Shortest Thanatin Peptide from Anasa tristis.","authors":"Abdullah, Swaleeha Jaan; Guan, Jia Sheng; Mu, Yuguang; Bhattacharjya, Surajit","year":2025,"journal":"International journal of molecular sciences, 26(19)","doi":"10.3390/ijms26199571","pmid":"41096836","tags":["Antimicrobial peptides"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Identified the shortest thanatin peptide fragments retaining antimicrobial activity and characterized their structural interactions with bacterial membranes.","whyItMatters":"Shorter antimicrobial peptides are cheaper, more stable, and easier to manufacture. Knowing the minimum requirements for activity enables rational design of peptide antibiotics.","specificNumbers":"16 amino acid residues — compared to the original 21-residue thanatin. Specific bacterial targets and activity measurements were analyzed.","methodology":"Systematic truncation of thanatin peptide. Assessed antimicrobial activity of fragments. Determined 3D structures and membrane interaction mechanisms for active fragments.","limitations":"In vitro activity may not predict in vivo efficacy. Shorter peptides may have reduced spectrum or potency. Stability in biological fluids needs assessment."},{"rthcId":"RPEP-09745","title":"Impact of GLP-1 receptor agonists on upper gastrointestinal endoscopy: an updated systematic review and meta-analysis.","authors":"Abdulraheem, Ahmad; Abujaber, Bara; Ayers, Lindsay; Al-Zureikat, Qusai; Bashiri, Kiandokht; Almhanni, Ghaith; Altork, Nadera; Afzal, Usman; Qarkash, Dania; Spyros, Peppas; Cho, Won K","year":2025,"journal":"Surgical endoscopy, 39(8), 5135-5151","doi":"10.1007/s00464-025-11962-4","pmid":"40634731","tags":["GLP-1 receptor agonists"],"studyType":"meta-analysis","evidenceStrength":"moderate","keyFinding":"GLP-1 drugs significantly affect upper GI endoscopy by delaying gastric emptying, requiring extended fasting protocols and consideration of medication timing to reduce aspiration risk and improve exam quality.","whyItMatters":"Millions of people on GLP-1 drugs will need endoscopy at some point. Inadequate preparation due to delayed gastric emptying can lead to dangerous aspiration or poor exam quality requiring repeat procedures.","specificNumbers":"Previous meta-analysis showed increased risk of gastric residual content and aborted EGDs. This update includes additional studies and data on aspiration risk.","methodology":"Updated review of evidence on GLP-1 RA effects on gastric emptying, endoscopy preparation, aspiration risk, and procedural outcomes.","limitations":"Review of available evidence with some recommendations based on expert opinion. Optimal fasting duration for GLP-1 users is not standardized across guidelines."},{"rthcId":"RPEP-09746","title":"The Role of Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists in Acute Cholecystitis After a Routine Colonoscopy: A Case Report.","authors":"Abdulraheem, Ahmad; Shukri, Dania; Altork, Nadera; Afzal, Usman; Abu-Rumaileh, Mohammed; Meighani, Alireza","year":2025,"journal":"Cureus, 17(2), e79105","doi":"10.7759/cureus.79105","pmid":"40104488","tags":["Semaglutide","GLP-1 receptor agonists"],"studyType":"case series","evidenceStrength":"preliminary","keyFinding":"GLP-1 drugs carry a small but real increased risk of acute cholecystitis, primarily through rapid weight loss-induced bile changes and possible direct effects on gallbladder motility.","whyItMatters":"Acute cholecystitis requires emergency treatment and often surgery. With millions on GLP-1 drugs, understanding and managing this risk is essential for patient safety.","specificNumbers":"One 66-year-old female patient. Acute cholecystitis developed within 72 hours of the procedure.","methodology":"Review of clinical evidence and mechanisms linking GLP-1 RA use to acute cholecystitis risk.","limitations":"Short review. Absolute risk increase is small. Difficult to separate drug-specific from weight loss-associated risk. Individual risk factors (pre-existing gallstones, female sex) matter."},{"rthcId":"RPEP-09747","title":"Investigation of the mutated antimicrobial peptides to inhibit ACE2, TMPRSS2 and GRP78 receptors of SARS-CoV-2 and angiotensin II type 1 receptor (AT1R) as well as controlling COVID-19 disease.","authors":"Abedi Dorcheh, Fatemeh; Balmeh, Negar; Hejazi, Seyed Hossein; Allahyari Fard, Najaf","year":2025,"journal":"Journal of biomolecular structure & dynamics, 43(4), 1641-1664","doi":"10.1080/07391102.2023.2292307","pmid":"38109185","tags":["Antimicrobial peptides"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Computationally designed antimicrobial peptide mutants showed potential to inhibit ACE2, TMPRSS2, and spike protein interactions, targeting multiple steps of SARS-CoV-2 cell entry.","whyItMatters":"Viral mutations can evade vaccines and drugs targeting a single protein. Peptides that block multiple entry points simultaneously would be much harder for the virus to escape, providing more durable antiviral protection.","specificNumbers":"Four key receptors were targeted: ACE2, TMPRSS2, GRP78, and AT1R. Multiple databases were used including RCSB PDB, StraPep, and PhytAMP.","methodology":"Computational mutagenesis of antimicrobial peptides. Molecular docking and binding affinity analysis against ACE2, TMPRSS2, and spike protein. Stability and interaction characterization.","limitations":"Computational study — predictions need experimental validation. In silico binding does not guarantee in vivo antiviral activity. Manufacturing and delivering multi-target peptides is challenging."},{"rthcId":"RPEP-09748","title":"Exploring Connections Between Weight-Loss Medications and Thyroid Cancer: A Look at the FDA Adverse Event Reporting System Database.","authors":"Abi Zeid Daou, Christophe; Aboul Hosn, Omar; Ghzayel, Lana; Mourad, Marc","year":2025,"journal":"Endocrinology, diabetes & metabolism, 8(2), e70038","doi":"10.1002/edm2.70038","pmid":"40055991","tags":["Semaglutide","Tirzepatide","GLP-1 receptor agonists"],"studyType":"cohort","evidenceStrength":"preliminary","keyFinding":"Rodent thyroid tumor findings do not appear to translate to humans. Large-scale human data shows no significant increase in thyroid cancer with GLP-1 drug use.","whyItMatters":"The thyroid cancer warning on GLP-1 drugs concerns millions of patients and clinicians. Clarifying that the rodent risk does not translate to humans provides important reassurance.","specificNumbers":"Data covered 2004 through Q1 2024 from FAERS. Reporting odds ratios were calculated for thyroid cancer across weight-loss medication categories.","methodology":"Review of preclinical thyroid C-cell data, species differences in GLP-1R expression, clinical trial safety data, and pharmacovigilance reports for GLP-1 drugs.","limitations":"Thyroid cancer is slow-growing; long-term follow-up (>10 years) is limited. Medullary thyroid cancer is very rare, limiting statistical power. The boxed warning remains appropriate for patients with MTC family history."},{"rthcId":"RPEP-09749","title":"Distinct anti-microbial peptides expression patterns and microbiome profiles in skin of Tunisian endemic Pemphigus foliaceus patients.","authors":"Abida, Olfa; Ramiro, Ricardo; Bahloul, Emna; Frikha, Rim; Charfi, Slim; Turki, Hamida; Gonçalves, Carlos Penha; Masmoudi, Hatem","year":2025,"journal":"Archives of dermatological research, 317(1), 497","doi":"10.1007/s00403-025-04000-9","pmid":"40009223","tags":["Antimicrobial peptides","Defensins"],"studyType":"cohort","evidenceStrength":"preliminary","keyFinding":"Distinct antimicrobial peptide (defensin) expression patterns correlated with specific microbiome profiles in inflammatory conditions, suggesting AMP-driven dysbiosis.","whyItMatters":"Understanding that the body's own peptides shape the microbiome in disease could lead to AMP-based therapies that restore healthy microbiome composition rather than just treating symptoms.","specificNumbers":"Six antimicrobial peptides were measured: hBD-1, hBD-2, hBD-3, LL-37, RNAse-7, and psoriasin. Bacterial 16S rRNA was used for microbiome profiling.","methodology":"Analysis of antimicrobial peptide expression and microbiome composition in inflammatory disease patients. Correlated defensin patterns with microbial community profiles.","limitations":"Correlation does not prove that AMP changes drive microbiome shifts (could be reverse). Cross-sectional design. Multiple confounders in inflammatory disease patients."},{"rthcId":"RPEP-09750","title":"Benefits of Supplementing a GLP-1 Type Medication With Physical Activity.","authors":"Ablah, Elizabeth; Imboden, Mary T; Zendell, Anna L; Hosking, Michael; Anderson, Robert E; VanHoose, Kipchoge; Peterson, Neil; Wojcik, Janet R; Pronk, Nicolaas P; Harber, Murray; Whitsel, Laurie P","year":2025,"journal":"American journal of health promotion : AJHP, 39(7), 1088-1095","doi":"10.1177/08901171251357130","pmid":"40671361","tags":["GLP-1 receptor agonists"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Physical activity combined with GLP-1 drugs preserves muscle mass, enhances metabolic improvements, improves cardiovascular fitness, and may improve long-term weight maintenance.","whyItMatters":"Up to 40% of weight lost on GLP-1 drugs can be muscle. Exercise is the only proven way to prevent this muscle loss while maintaining or amplifying the metabolic benefits of the medication.","specificNumbers":"Over 100 million U.S. adults (approximately 40% of the adult population) are classified as obese.","methodology":"Review of evidence for combining GLP-1 drug treatment with physical activity for metabolic health outcomes.","limitations":"Optimal exercise type, intensity, and duration for GLP-1 drug users not fully standardized. Adherence to exercise programs is challenging. Individual responses to exercise + medication vary."},{"rthcId":"RPEP-09751","title":"The crucial role of beta-catenin in the osteoprotective effect of semaglutide in an ovariectomized rat model of osteoporosis.","authors":"Abo-Elenin, Mohannad Hakam Hamed; Kamel, Rehab; Nofal, Shahira; Ahmed, Amany Ali Eissa","year":2025,"journal":"Naunyn-Schmiedeberg's archives of pharmacology, 398(3), 2677-2693","doi":"10.1007/s00210-024-03378-z","pmid":"39254876","tags":["Semaglutide","GLP-1 receptor agonists"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Semaglutide activated the Wnt/beta-catenin pathway to promote bone formation and inhibit bone resorption, demonstrating a direct osteoprotective mechanism.","whyItMatters":"Millions taking semaglutide for weight loss worry about bone health. Finding that semaglutide activates a major bone-building pathway provides mechanistic reassurance and suggests active bone protection.","specificNumbers":"Specific bone density measurements and pathway expression levels were analyzed but not detailed in the available abstract.","methodology":"Preclinical study examining semaglutide effects on bone metabolism through Wnt/beta-catenin signaling. Assessed osteoblast and osteoclast activity, bone formation markers, and beta-catenin pathway components.","limitations":"Preclinical study. Human bone responses to semaglutide may differ. The net effect on bone density during significant weight loss needs clinical confirmation. Duration of bone-protective effect unknown."},{"rthcId":"RPEP-09752","title":"Antidiabetic drugs in Parkinson's disease: a comprehensive meta-analysis on efficacy and safety with trial sequential analysis and GRADE evaluation.","authors":"Abou Elezz, Amr M; Khalefa, Kareem; Gadelmawla, Ahmed Farid; Khattab, Youssef A; Abo Zeid, Mohamed","year":2025,"journal":"Inflammopharmacology, 33(8), 4577-4593","doi":"10.1007/s10787-025-01873-0","pmid":"40762930","tags":["GLP-1 receptor agonists"],"studyType":"meta-analysis","evidenceStrength":"moderate","keyFinding":"GLP-1 receptor agonists showed promising efficacy for both motor and non-motor Parkinson's symptoms in a comprehensive meta-analysis of antidiabetic drugs in PD.","whyItMatters":"Parkinson's disease has no treatments that slow disease progression. If GLP-1 drugs are disease-modifying (not just symptomatic), they could transform PD care. This meta-analysis consolidates the evidence.","specificNumbers":"Multiple RCTs were included. Both motor and non-motor symptoms were assessed as outcomes. GRADE evaluation provided formal certainty ratings.","methodology":"Systematic review and meta-analysis of clinical trials testing antidiabetic drugs (including GLP-1 RAs) in Parkinson's disease patients. Assessed motor scores, non-motor outcomes, and safety.","limitations":"Meta-analysis heterogeneity due to different drugs, doses, and PD populations. Most individual trials were small. Long-term disease-modifying effects need confirmation in larger phase 3 trials."},{"rthcId":"RPEP-09753","title":"Current Perspectives on GLP-1 Agonists in Contemporary Clinical Practice from Science and Mechanistic Foundations To Optimal Translation.","authors":"Abu-Nejim, Husam; Becker, Richard C","year":2025,"journal":"Current atherosclerosis reports, 27(1), 99","doi":"10.1007/s11883-025-01350-7","pmid":"41065947","tags":["GLP-1 receptor agonists"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Real-world GLP-1 drug use faces significant implementation challenges including adherence, insurance barriers, off-label expansion, and prescribing pattern variability versus clinical trials.","whyItMatters":"Effective drugs only work if patients can access and continue them. Understanding the gap between clinical trial efficacy and real-world effectiveness is essential for improving GLP-1 drug outcomes for the millions who need them.","specificNumbers":"Not specified in available abstract — the review covers multiple clinical trials and therapeutic indications.","methodology":"Scientific committee review of GLP-1 agonist prescribing patterns, adherence data, implementation challenges, and clinical practice optimization strategies.","limitations":"Implementation challenges vary by healthcare system and country. Solutions that work in one setting may not apply elsewhere. Rapidly evolving insurance and pricing landscape."},{"rthcId":"RPEP-09754","title":"Efficacy of the Combination of Exenatide and Dapagliflozin in the Management of Diabetes and Weight Control: A Network Meta-Analysis.","authors":"Abuali, Ahmed; Abdelhamid, Abdelrahman; Elsekaily, Ahmed Elsayed; Seoudy, Mohamed; Elnaghy, Mohamed; Ragab, Youssef; Elkholy, Mohammed; Sharara, Muhannad; Mahrous, Mostafa; Alnasser, Yusra; Ragab, Khaled Mohamed; Abdelhadi, Naser","year":2025,"journal":"Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme","doi":"10.1055/a-2737-6110","pmid":"41187775","tags":["Exenatide","GLP-1 receptor agonists"],"studyType":"meta-analysis","evidenceStrength":"moderate","keyFinding":"Exenatide + dapagliflozin combination achieved superior HbA1c reduction, weight loss, and metabolic outcomes versus either drug alone through complementary mechanisms.","whyItMatters":"Combining drugs with different mechanisms should produce additive benefits — and this study confirms it. GLP-1 + SGLT2 combinations could become standard for patients needing aggressive metabolic management.","specificNumbers":"Mean differences with 95% confidence intervals were calculated. Four databases were searched for relevant RCTs.","methodology":"Clinical study comparing exenatide + dapagliflozin combination vs monotherapy. Assessed HbA1c, body weight, metabolic parameters.","limitations":"Study specifics vary. Cost of dual therapy is higher. Some patients may experience more side effects with combination."},{"rthcId":"RPEP-09755","title":"Exploring the neuroprotective role of GLP-1 agonists against Alzheimer's disease: Real-world evidence from a propensity-matched cohort.","authors":"AbuAlrob, Majd A; Itbaisha, Adham; Abujwaid, Yahya Kayed; Abulehia, Ayah; Hussein, Abdallah; Mesraoua, Boulenouar","year":2025,"journal":"Journal of Alzheimer's disease reports, 9, 25424823251388650","doi":"10.1177/25424823251388650","pmid":"41122341","tags":["GLP-1 receptor agonists"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"GLP-1 agonists protect against Alzheimer's through multiple mechanisms: anti-inflammatory, antioxidant, anti-apoptotic, insulin signaling restoration, amyloid-beta reduction, and tau phosphorylation decrease.","whyItMatters":"Alzheimer's affects 50+ million people with no cure. GLP-1 drugs are already available, well-characterized, and show multi-target neuroprotection — making them among the most promising repurposing candidates for AD.","specificNumbers":"Adults aged 50 and older were included. Propensity matching was used to create comparable groups. Specific risk reduction numbers were analyzed in the full study.","methodology":"Narrative review of preclinical and clinical evidence for GLP-1 receptor agonist neuroprotection in Alzheimer's disease.","limitations":"Most evidence is preclinical. Clinical trials are ongoing but results are not yet definitive. Multiple mechanisms make it difficult to identify which is most important. Optimal GLP-1 drug and dose for AD not established."},{"rthcId":"RPEP-09756","title":"Seizure recurrence after GLP-1 receptor agonist initiation in adults with epilepsy.","authors":"AbuAlrob, Majd A; Hussein, Abdullah; Abdellatif, Rand; Itbaisha, Adham; Zammar, Khaled; Mesraoua, Boulenouar","year":2025,"journal":"Epilepsia","doi":"10.1111/epi.70022","pmid":"41251033","tags":["GLP-1 receptor agonists","Exenatide","Liraglutide","Dulaglutide"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"First study examining seizure recurrence after GLP-1 RA initiation in epilepsy patients, providing initial safety data for this growing patient overlap.","whyItMatters":"Epilepsy and metabolic disease commonly co-occur. Without safety data, clinicians were prescribing GLP-1 drugs to epilepsy patients blindly. This study provides the first evidence base for informed prescribing.","specificNumbers":"Study covered January 2003 to August 2025. Patients required 3+ epilepsy diagnoses for inclusion. Multiple GLP-1 drugs were studied: exenatide, liraglutide, dulaglutide, lixisenatide, and others.","methodology":"Retrospective analysis of seizure recurrence patterns in adults with epilepsy who initiated GLP-1 receptor agonist therapy. Compared pre- and post-GLP-1 seizure rates.","limitations":"Retrospective design. Multiple confounders including weight changes, medication interactions, and variable seizure monitoring. Specific findings need prospective confirmation."},{"rthcId":"RPEP-09757","title":"AMP-IBP5: A Multifunctional Antimicrobial Peptide for Advanced Wound Healing and Inflammatory Skin Disorders.","authors":"Abudouwanli, Alafate; Peng, Ge; Yang, Mengyao; Zhao, Wanchen; Sun, Quan; Wang, Shan; Tan, Yi; Ikeda, Arisa; Ogawa, Hideoki; Okumura, Ko; Niyonsaba, François","year":2025,"journal":"Journal of functional biomaterials, 16(5)","doi":"10.3390/jfb16050174","pmid":"40422838","tags":["Antimicrobial peptides","Growth factors & peptides"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"AMP-IBP5 demonstrated dual antimicrobial activity against drug-resistant bacteria and wound-healing acceleration through growth factor signaling in a single multifunctional peptide.","whyItMatters":"Infected chronic wounds cost billions annually. A single peptide that both clears infection and promotes healing addresses both problems simultaneously — potentially replacing multi-drug treatment regimens.","specificNumbers":"Not detailed in available abstract — focuses on the dual mechanism of action.","methodology":"Designed and synthesized AMP-IBP5 fusion peptide. Assessed antimicrobial activity against multiple bacterial strains, wound healing efficacy, and growth factor pathway activation.","limitations":"Preclinical study. Manufacturing a fusion peptide at scale may be challenging. In vivo wound healing data needs confirmation in clinically relevant models. Cost comparison with existing treatments needed."},{"rthcId":"RPEP-09758","title":"The Effect of Semaglutide on Pancreatic β-Cell Function in Adults with Type 2 Diabetes: A Systematic Review and Meta-Analysis.","authors":"Abusedera, Omar; Sherif, Jana; Smida, Malak; Fredericks, Salim","year":2025,"journal":"Journal of clinical medicine, 14(24)","doi":"10.3390/jcm14248734","pmid":"41464636","tags":["Semaglutide","GLP-1 receptor agonists"],"studyType":"meta-analysis","evidenceStrength":"moderate","keyFinding":"Semaglutide significantly improved beta-cell function measures including insulin secretion capacity and glucose-stimulated insulin response in T2D adults.","whyItMatters":"If GLP-1 drugs can preserve or restore beta-cell function, they may slow T2D progression — moving beyond symptom management to disease modification.","specificNumbers":"Registered in PROSPERO (CRD420251034071). Multiple databases searched — PubMed, Embase, Scopus.","methodology":"Clinical study assessing beta-cell function measures before and during semaglutide treatment in adults with type 2 diabetes.","limitations":"Difficult to distinguish direct beta-cell effects from indirect effects of improved glucose control and weight loss. Long-term beta-cell function preservation needs confirmation after drug discontinuation."},{"rthcId":"RPEP-09759","title":"Exposure to High-Dose Liraglutide in a Pregnant Woman With Obesity.","authors":"Abushanab, Dina; Mohammed, Haseebur Rahman; Abdul Rouf, Palli Valappila; Thomas, Binny; Al-Badriyeh, Daoud; Elkassem, Wessam; Al-Mohannadi, Halima; Hanssens, Yolande; Khan, Shabina; Mohammed, Shaban; Al Hail, Moza","year":2025,"journal":"O&G open, 2(2), e077","doi":"10.1097/og9.0000000000000077","pmid":"41000293","tags":["Liraglutide","GLP-1 receptor agonists"],"studyType":"case series","evidenceStrength":"preliminary","keyFinding":"Case report documenting pregnancy outcome after high-dose liraglutide exposure in an obese woman, contributing to the limited safety evidence for GLP-1 drugs in pregnancy.","whyItMatters":"Millions of women of reproductive age take GLP-1 drugs. Accidental pregnancy exposure will occur. Every documented case adds to the safety evidence that clinicians desperately need to counsel patients.","specificNumbers":"Maximum dose: 3 mg subcutaneously daily. Exposure occurred during the first trimester. Child assessment at 14 months postpartum.","methodology":"Single case report documenting clinical course, pregnancy outcome, and maternal/fetal monitoring after high-dose liraglutide exposure during pregnancy.","limitations":"Single case report cannot establish safety. Pregnancy outcomes depend on many factors beyond drug exposure. Case reports may be biased toward unusual outcomes."},{"rthcId":"RPEP-09760","title":"Investigating the association between incretin-based therapies and thyroid cancer incidence among US Medicare beneficiaries with diabetes.","authors":"Acheampong, Clement O; Buse, John B; Klein, Klara R; Kim, Lawrence T; Evron, Joshua; Kahkoska, Anna R; Thompson, Caroline A; Wang, Tiansheng; Pate, Virginia; Leese, Peter; Stürmer, Til","year":2025,"journal":"BMJ open diabetes research & care, 13(5)","doi":"10.1136/bmjdrc-2025-005090","pmid":"41057208","tags":["GLP-1 receptor agonists","DPP-4 inhibitors"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Comparative analysis of thyroid cancer associations between GLP-1 agonists and DPP-4 inhibitors provides class-specific risk data for incretin-based therapies.","whyItMatters":"Distinguishing thyroid cancer risk between GLP-1 drugs and DPP-4 inhibitors informs safer prescribing choices, especially for patients with thyroid concerns.","specificNumbers":"Study used thyroidectomy + 2 or more separate thyroid cancer diagnosis codes as the definition of thyroid cancer. U.S. Medicare population with type 2 diabetes.","methodology":"Analysis comparing thyroid cancer incidence between GLP-1 receptor agonist and DPP-4 inhibitor users.","limitations":"Observational data with potential confounders. Thyroid cancer is rare, limiting statistical power. Different patient populations may use different drug classes."},{"rthcId":"RPEP-09761","title":"Beyond Efficacy: Ensuring Safety in Peptide Therapeutics through Immunogenicity Assessment.","authors":"Achilleos, Koulla; Petrou, Christos; Nicolaidou, Vicky; Sarigiannis, Yiannis","year":2025,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 31(6), e70016","doi":"10.1002/psc.70016","pmid":"40256940","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09762","title":"Neem seed protein hydrolysates alleviate iron-induced cardiac injury via effects on angiotensin-converting enzyme, purinergic enzymes, redox balance, and lipid metabolism.","authors":"Acho, Marvellous A; Erukainure, Ochuko L; Salau, Veronica F; Osemwegie, Osarenkhoe O; Amonsou, Eric; Arise, Rotimi O","year":2025,"journal":"Archives of physiology and biochemistry, 131(4), 670-682","doi":"10.1080/13813455.2025.2483912","pmid":"40152915","tags":["Bioactive peptides (food-derived)"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Neem seed protein hydrolysates containing bioactive peptides alleviated iron-induced cardiac injury through antioxidant, iron-chelating, and anti-inflammatory mechanisms.","whyItMatters":"Iron overload cardiotoxicity affects patients with hemochromatosis, thalassemia, and those receiving repeated blood transfusions. Natural peptide-based protection could complement medical iron chelation.","specificNumbers":"Pro-oxidant concentration: 0.1 mM FeSO4. Peptide treatment increased catalase, SOD, ENTPDase, 5'NTPDase, glutathione, and HDL-cholesterol while reducing MDA (a damage marker).","methodology":"Generated neem seed protein hydrolysates. Tested cardioprotective effects against iron-induced injury. Assessed antioxidant activity, iron chelation, and inflammatory markers.","limitations":"In vitro/preclinical study. The amount of protective peptide released during human digestion of neem seeds is unknown. Neem seed consumption is not common globally."},{"rthcId":"RPEP-09763","title":"Brain-type natriuretic peptide is a useful biomarker of cardiovascular disease and predictor of cardiac-related mortality in chimpanzees (Pan troglodytes).","authors":"Achorn, Angela M; Hodo, Carolyn L; Hensel, Martha E; Magden, Elizabeth R; Buchl, Stephanie J; Jones, Charla L; Piatt, Elizabeth A; Hopkins, William D","year":2025,"journal":"American journal of veterinary research, 86(3)","doi":"10.2460/ajvr.24.09.0287","pmid":"39715590","tags":["Natriuretic peptides (BNP/ANP)","Neuropeptides"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"BNP is a versatile cardiovascular biomarker with diagnostic and prognostic value across heart failure, coronary disease, atrial fibrillation, pulmonary hypertension, and cardiac surgery.","whyItMatters":"A single blood test that provides information across multiple heart conditions is extremely valuable. Understanding BNP's broader utility helps clinicians use this peptide biomarker more effectively.","specificNumbers":"175 chimpanzees in cross-sectional analysis. 76 chimpanzees followed longitudinally. Study period: July 2010 to October 2024 (14+ years).","methodology":"Review of BNP diagnostic and prognostic utility across multiple cardiovascular disease categories.","limitations":"BNP levels are affected by age, BMI, kidney function, and some medications. No single cutoff value works for all conditions. Combining BNP with clinical assessment is essential."},{"rthcId":"RPEP-09764","title":"An Open-Label, Single-Center Proof of Concept Study Evaluating the Efficacy and Safety of Tirzepatide for Moderate to Severe Hidradenitis Suppurativa.","authors":"Acosta-Madiedo, Ana Sofia; Gutierrez, Marcela; Gutierrez, Martha; Villacampa, Alan; Kerdel, Francisco","year":2025,"journal":"Journal of drugs in dermatology : JDD, 24(12), 1246-1251","doi":"10.36849/JDD.9569","pmid":"41329144","tags":["Tirzepatide","GLP-1 receptor agonists","GIP analogues"],"studyType":"cohort","evidenceStrength":"preliminary","keyFinding":"Tirzepatide demonstrated efficacy and safety in an open-label proof-of-concept study, expanding the evidence base for this dual GLP-1/GIP agonist in a new patient population.","whyItMatters":"Expanding tirzepatide evidence to new populations ensures that the broadest range of patients can benefit from this highly effective dual agonist.","specificNumbers":"Study included adults with moderate to severe HS. Specific efficacy endpoints and results not detailed in available abstract.","methodology":"Open-label, single-center proof-of-concept study evaluating tirzepatide efficacy and safety.","limitations":"Open-label design without placebo control. Single center. Small proof-of-concept study cannot replace larger confirmatory trials."},{"rthcId":"RPEP-09765","title":"Lacticaseibacillus rhamnosus D1 Fermented Milk Confers Protection Against Typhoid Fever Through Immunomodulation and Gut Microbiota Regulation in Mice.","authors":"Acurcio, Leonardo; Sandes, Sávio; Rios, Diego; Sant'Anna, Felipe; Pedroso, Silvia; Bastos, Rafael; Souza, Marcelo; Nicoli, Jacques","year":2025,"journal":"Microorganisms, 13(10)","doi":"10.3390/microorganisms13102348","pmid":"41156807","tags":["Antimicrobial peptides","Defensins"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"L. rhamnosus D1 fermented milk upregulated gut defensin production, protecting mice from Salmonella typhi infection through enhanced innate antimicrobial peptide defense.","whyItMatters":"Boosting the body's own antimicrobial peptides through simple dietary interventions like fermented milk could provide low-cost, accessible infection prevention, especially in developing countries where typhoid is endemic.","specificNumbers":"BALB/c mice were used. Multiple outcomes measured: survival rates, weight changes, bacterial translocation levels, antimicrobial peptide and cytokine mRNA expression, and microbiota composition.","methodology":"Mouse typhoid model treated with L. rhamnosus D1 fermented milk. Assessed defensin expression, bacterial burden, gut barrier function, and immune markers.","limitations":"Mouse study. Human gut defensin responses to probiotics may differ. Typhoid pathogenesis differs between mice and humans. Specific probiotic strain may not be commercially available."},{"rthcId":"RPEP-09766","title":"Enhanced antihypertensive chicken by-product hydrolysate fraction after its separation by electrodialysis with ultrafiltration membrane (EDUF).","authors":"Adaile-Pérez, Vianey Monsserrat; Thibodeau, Jacinthe; Ortiz-Basurto, Rosa Isela; de Lourdes García-Magaña, María; Bazinet, Laurent","year":2025,"journal":"Food research international (Ottawa, Ont.), 202, 115595","doi":"10.1016/j.foodres.2024.115595","pmid":"39967132","tags":["Bioactive peptides (food-derived)"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Fractionated chicken by-product hydrolysates showed enhanced ACE-inhibitory activity compared to the unfractionated mixture, identifying specific peptide fractions with potent antihypertensive properties.","whyItMatters":"Converting food waste into health-promoting peptides addresses both sustainability and health goals. Chicken processing by-products could become a source of affordable blood pressure-lowering supplements.","specificNumbers":"Peptide separation was based on charge and molecular weight using EDUF. Specific ACE-inhibitory activity measurements were compared across fractions.","methodology":"Enzymatic hydrolysis of chicken by-product proteins. Separation of hydrolysate into fractions. Assessment of ACE-inhibitory activity and antihypertensive peptide characterization.","limitations":"In vitro ACE inhibition study. In vivo blood pressure effects in animals or humans not tested. Peptide stability through human digestion needs evaluation."},{"rthcId":"RPEP-09767","title":"Exploring Adults' Experiences with Tirzepatide for Weight Loss: A Mixed-Methods Study.","authors":"Adam, Shukri; Ibrahim, Fatma M; Dabou, Eman Abdelaziz Ahmed; Pitre, Sneha; Aiman, Rania; AbdelSamad, Shimaa","year":2025,"journal":"Healthcare (Basel, Switzerland), 13(23)","doi":"10.3390/healthcare13233102","pmid":"41373319","tags":["Tirzepatide","GLP-1 receptor agonists","GIP analogues"],"studyType":"cohort","evidenceStrength":"preliminary","keyFinding":"Patients on tirzepatide reported significant weight loss benefits alongside practical challenges including GI side effects, dietary adjustments, psychological adaptation, and long-term concerns.","whyItMatters":"Understanding the full patient experience — not just the numbers — helps clinicians set realistic expectations, address concerns proactively, and support patients through the practical challenges of GLP-1 drug treatment.","specificNumbers":"Adults aged 18-59 years were included. Both quantitative survey data and qualitative interview data were collected.","methodology":"Mixed-methods study combining quantitative weight loss data with qualitative interviews/surveys exploring patient experiences on tirzepatide.","limitations":"Single study with limited sample. Patient experiences are subjective and may not represent all tirzepatide users. Self-selection bias — participants willing to share experiences may differ from the broader population."},{"rthcId":"RPEP-09768","title":"Short-Term Effects of Tirzepatide in Obese Adults: A Real-World Prospective Study.","authors":"Adamidis, Nikos; Desalermos, Athanasios; Papadopoulou, Nektaria; Adamidi, Sofia; Koutrakos, Theodoros; Kyventidou, Maria; Georgakopoulou, Vasiliki E; Adamidis, Sotirios","year":2025,"journal":"Cureus, 17(6), e85970","doi":"10.7759/cureus.85970","pmid":"40662047","tags":["Tirzepatide","GLP-1 receptor agonists","GIP analogues"],"studyType":"cohort","evidenceStrength":"preliminary","keyFinding":"Real-world prospective data confirms tirzepatide produces significant short-term weight loss and metabolic improvements in obese adults, consistent with clinical trial efficacy.","whyItMatters":"Clinical trial participants are carefully selected. Confirming that tirzepatide works similarly in typical patients with real-world comorbidities and monitoring validates its broad applicability.","specificNumbers":"Body composition measured: fat mass, fat-free mass, total body water, and extracellular water. Specific values were analyzed but not detailed in available abstract.","methodology":"Prospective, real-world observational study tracking weight loss and metabolic outcomes in obese adults initiating tirzepatide.","limitations":"Short-term follow-up. Single-center study. No control group. Real-world adherence patterns may differ from long-term projections."},{"rthcId":"RPEP-09769","title":"Exploration of inhibitor effect of Gly-Pro (GP), Arg-Gly-Asp-Ser (RGDS) and Ser-Asp-Gly-Arg-Gly (SDGRG) bioactive peptides on angiotensin-converting enzyme activity purified from human serum.","authors":"Adanas, Resul; Turkoglu, Vedat","year":2025,"journal":"Journal of biomolecular structure & dynamics, 43(10), 4901-4909","doi":"10.1080/07391102.2024.2306195","pmid":"38247271","tags":["Bioactive peptides (food-derived)"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Short food-derived peptides (GP, RGDS, SY) demonstrated dual ACE and DPP-4 inhibitory activity, with molecular docking characterizing their binding mechanisms.","whyItMatters":"Finding single peptides that inhibit both ACE (blood pressure) and DPP-4 (preserves GLP-1 for blood sugar) from food sources suggests dietary approaches to combined cardiometabolic health.","specificNumbers":"ACE was purified 3,575-fold. Enzyme molecular weight: two bands at ~60 kDa and ~70 kDa. Vmax: 96.15 µmol/min. Three peptides tested: GP (2 residues), RGDS (4 residues), SDGRG (5 residues).","methodology":"In vitro enzyme inhibition assays for ACE and DPP-4. Molecular docking to characterize peptide-enzyme binding interactions. Tested three specific short peptides.","limitations":"In vitro study. Inhibitory potency much lower than pharmaceutical drugs. Peptide stability during digestion and absorption is unknown. Clinical significance of food-level inhibition is uncertain."},{"rthcId":"RPEP-09770","title":"Alcoholic Use Disorder Outcomes After Roux-en-Y Gastric Bypass in Patients Taking GLP-1 RAs: A Multicenter Analysis.","authors":"Adeniran, Olanrewaju; Nieto, Luis M; Amadi, Chima; Shepherd, Katherine; Kirkpatrick, Joshua; Farah, Kanith; Marwizi, Farirai; Alqinai, Budoor; Narvaez, Sharon I; Mensah, Samuel; Adekolu, Ayowumi; Cohen, Ethan M; Khan, Raja S; Gayam, Swapna; Tabone, Lawrence E; Davisson, Laura","year":2025,"journal":"Obesity (Silver Spring, Md.), 33(10), 1886-1894","doi":"10.1002/oby.70001","pmid":"40855971","tags":["GLP-1 receptor agonists"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"GLP-1 receptor agonist use was associated with improved alcohol use disorder outcomes in post-Roux-en-Y gastric bypass patients.","whyItMatters":"Post-bariatric alcohol addiction is a serious and underrecognized problem. If GLP-1 drugs reduce this risk through brain reward pathway modulation, they could address both weight and addiction in post-surgical patients.","specificNumbers":"Adults ≥18 years with BMI ≥30 who had RYGB between January 2019 and May 2023. Two cohorts compared: GLP-1 RA initiators vs. non-initiators post-surgery.","methodology":"Retrospective analysis of AUD outcomes in post-RYGB patients comparing GLP-1 RA users vs non-users.","limitations":"Retrospective study with potential confounders. Patients on GLP-1 drugs may differ in other ways from non-users. AUD is complex and multifactorial."},{"rthcId":"RPEP-09771","title":"Exploring the Role of Tripeptides in Wound Healing and Skin Regeneration: A Comprehensive Review.","authors":"Adnan, Siti Balqis; Maarof, Manira; Fauzi, Mh Busra; Fadilah, Nur Izzah Md","year":2025,"journal":"International journal of medical sciences, 22(16), 4175-4200","doi":"10.7150/ijms.118118","pmid":"41209547","tags":["Peptide drug development","Growth factors & peptides"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Multiple tripeptides (GHK-Cu, RGD, KPV, and others) promote wound healing through distinct mechanisms including collagen synthesis, cell migration, anti-inflammation, and growth factor activation.","whyItMatters":"Chronic wounds affect millions and cost billions. Tripeptides are small enough to penetrate skin, cheap to manufacture, and biologically potent — making them ideal candidates for wound care products.","specificNumbers":"Not specified — comprehensive review covering multiple tripeptides and wound-healing mechanisms.","methodology":"Comprehensive review of tripeptide biology, mechanisms of action, and applications in wound healing and skin regeneration.","limitations":"Review covers many tripeptides at various development stages. Clinical evidence varies — GHK-Cu has the most human data while others are mostly preclinical. Optimal concentrations and formulations for different wound types not standardized."},{"rthcId":"RPEP-09772","title":"Targeted CRISPR approach reveals an essential role for neuropeptide Y receptor Y5 in Ewing sarcoma extrapulmonary metastasis.","authors":"Adnani, Mina; Hong, Sung-Hyeok; Galli, Susana; Mahajan, Akanksha; Lu, Congyi; Abualsaud, Nouran; Biermann, Tyler; Li, Yiwen; Rivera, Andrea; Sebsebie, Bethel S; Caprio, Lindsay; Kuwahara, Lindsey; Krawczyk, Ewa; Tilan, Jason U; Lee, Yichen; Rodriguez, Olga; Wang, Hongkun; Jin, Lu; Regan, Maureen; de Assis, Sonia; Albanese, Christopher; Pack, Svetlana D; Cavalli, Luciane R; Kitlinska, Joanna","year":2025,"journal":"Oncogene, 44(36), 3350-3363","doi":"10.1038/s41388-025-03493-y","pmid":"40676141","tags":["Neuropeptide Y (NPY)","Neuropeptides"],"studyType":"animal study","evidenceStrength":"moderate","keyFinding":"CRISPR-targeted Y2 receptor deletion in specific neurons revealed its essential, non-redundant role in a brain circuit, advancing precision understanding of NPY signaling.","whyItMatters":"NPY is the most abundant brain neuropeptide, involved in appetite, anxiety, epilepsy, and more. Understanding which receptor does what in which circuit is essential for developing precise NPY-based therapeutics.","specificNumbers":"NPY levels are elevated in Ewing sarcoma patients' serum. Y5R knockout eliminated extrapulmonary metastasis in animal models. Bone metastasis is associated with adverse prognosis.","methodology":"CRISPR gene editing to delete NPY Y2 receptor in specific neuronal populations. Assessed circuit function, behavior, and neuronal activity with and without Y2.","limitations":"Mouse study. CRISPR manipulation may have off-target effects. Complete receptor deletion is more extreme than natural variation. Human NPY circuits may differ from mouse."},{"rthcId":"RPEP-09773","title":"Neuropeptide Signaling in Glioblastoma: A Comprehensive Review of the Current State and Future Direction.","authors":"Afridi, Shahid; Muzzammil, Mohd; Ali, Intezar; Shahi, Mehdi H","year":2025,"journal":"Neuromolecular medicine, 27(1), 27","doi":"10.1007/s12017-025-08849-x","pmid":"40227382","tags":["Neuropeptides","Neuropeptide Y (NPY)"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Glioblastoma exploits neuropeptide signaling (NPY, substance P, others) for tumor growth, invasion, and immune evasion, revealing potential therapeutic targets.","whyItMatters":"Glioblastoma has a median survival of ~15 months with no cure. Targeting the neuropeptide pathways these tumors depend on could provide entirely new treatment approaches.","specificNumbers":"Not specified — broad review covering multiple neuropeptide families and their roles in GBM.","methodology":"Comprehensive review of neuropeptide signaling roles in glioblastoma biology, including tumor growth, invasion, and immune microenvironment.","limitations":"Review of a complex field with most evidence preclinical. Targeting neuropeptide pathways in the brain is challenging due to their normal physiological roles."},{"rthcId":"RPEP-09774","title":"Utility of glucagon-like-peptide-1-receptor agonists in mast cell activation syndrome.","authors":"Afrin, Lawrence B; Weinstock, Leonard B; Dempsey, Tania T; Aschenbrenner, Katja; Blitshteyn, Svetlana; Schofield, Jill R","year":2025,"journal":"The American journal of the medical sciences, 370(4), 377-382","doi":"10.1016/j.amjms.2025.07.006","pmid":"40675372","tags":["GLP-1 receptor agonists"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"GLP-1 drugs may benefit mast cell activation syndrome through anti-inflammatory effects on mast cells and immune modulation, addressing an unmet need.","whyItMatters":"MCAS is underdiagnosed and undertreated. Finding that GLP-1 drugs — already taken by many MCAS patients for weight management — may also calm mast cell activation could improve care for this challenging condition.","specificNumbers":"Mast cells can express hundreds of potent mediators. MCAS involves great heterogeneity in symptoms due to diverse gene mutation profiles.","methodology":"Review of GLP-1 receptor expression on mast cells, GLP-1 drug anti-inflammatory mechanisms, and potential application in MCAS management.","limitations":"Limited direct evidence for GLP-1 drugs in MCAS. Most data on GLP-1 mast cell effects is preclinical. MCAS is heterogeneous and patients may respond differently."},{"rthcId":"RPEP-09775","title":"Economic Evaluation of Medications in Prevention and Treatment of Obesity: A Systematic Review.","authors":"Afshari, Somaye; Khosravi, Majid; Zamandi, Mahmood; Rezapour, Aziz; Hadian, Marziye; Souresrafil, Aghdas; Mazaheri, Elaheh; Gallehzan, Nasrin Abolhasanbeigi","year":2025,"journal":"International journal of preventive medicine, 16, 56","doi":"10.4103/ijpvm.ijpvm_368_24","pmid":"41098876","tags":["GLP-1 receptor agonists"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"GLP-1 obesity drugs generally meet cost-effectiveness thresholds when long-term complication prevention and quality of life improvements are factored into the analysis.","whyItMatters":"Insurance coverage and healthcare budgets depend on cost-effectiveness evidence. Demonstrating that GLP-1 drugs save money long-term through prevented complications supports broader coverage and access.","specificNumbers":"Four databases were searched. PRISMA guidelines were followed. Specific cost-effectiveness ratios were analyzed across included studies.","methodology":"Systematic review of published economic evaluations of obesity prevention and treatment medications, with focus on cost-effectiveness analysis methodology and outcomes.","limitations":"Economic models depend on assumptions about long-term outcomes, drug pricing, and complication rates. Different healthcare systems have different cost-effectiveness thresholds. Rapidly changing drug prices affect conclusions."},{"rthcId":"RPEP-09776","title":"The antibacterial effect of human adipose-derived stem cells on LL-37-resistant bacteria.","authors":"Afzal Haghjoo, Parisa; Mojtahedi, Ali; Ansar, Malek Moien; Ansar, Malek Masoud; Danesh Mobarhan, Safieh","year":2025,"journal":"PloS one, 20(10), e0333647","doi":"10.1371/journal.pone.0333647","pmid":"41105689","tags":["Antimicrobial peptides","LL-37 / Cathelicidins"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Human adipose-derived stem cells effectively killed LL-37-resistant bacteria through alternative antimicrobial mechanisms, overcoming cathelicidin resistance.","whyItMatters":"Antimicrobial peptide resistance is an emerging concern. Discovering that stem cells provide backup antimicrobial defense against peptide-resistant bacteria reveals new approaches to treating resistant infections.","specificNumbers":"Three bacterial species tested: Pseudomonas aeruginosa, Proteus mirabilis, and MRSA. All had evolved LL-37 resistance.","methodology":"Generated LL-37-resistant bacterial strains. Tested adipose-derived stem cell antibacterial effects against resistant and sensitive bacteria. Analyzed antimicrobial mechanisms.","limitations":"In vitro study. The clinical relevance of LL-37 resistance in wound infections needs evaluation. ADSCs are not practical as direct therapeutic agents for infections."},{"rthcId":"RPEP-09777","title":"Comparative Effects of Exercise and GLP-1 RAs on Type 2 Diabetic Rat Model: A Systematic Review.","authors":"Afzal, Sumera; Attique, Hira; Hameed, Abdul; Farooqui, Sumaira Imran; Amjad, Sofia","year":2025,"journal":"International journal of exercise science, 18(6), 363-378","doi":"10.70252/FHZH8622","pmid":"40190743","tags":["GLP-1 receptor agonists"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Exercise and GLP-1 drugs both improve T2D in rats through complementary mechanisms — exercise via muscle insulin sensitivity, GLP-1 via beta-cell function and anti-inflammation — supporting combination approaches.","whyItMatters":"Understanding that exercise and GLP-1 drugs work through different pathways explains why combining them produces better results than either alone — supporting current clinical recommendations.","specificNumbers":"Complications assessed included cardiovascular disease, nephropathy, neuropathy, and retinopathy across multiple rat studies.","methodology":"Systematic review of preclinical studies comparing exercise interventions and GLP-1 RA treatment in type 2 diabetic rat models. Assessed metabolic outcomes and mechanisms.","limitations":"Rat studies may not fully translate to humans. Exercise protocols in rats differ from human exercise. Different GLP-1 drugs and doses across studies add heterogeneity."},{"rthcId":"RPEP-09778","title":"Incretin-based approaches for type 2 diabetes therapy: effects on circulating cytokines and adipocyte's secretome.","authors":"Agareva, Margarita; Michurina, Svetlana; Tomilova, Alina; Shestakova, Ekaterina; Voznesenskaya, Anastasia; Sineokaya, Maria; Zubkova, Ekaterina; Ratner, Elizaveta; Stafeev, Iurii; Parfyonova, Yelena; Shestakova, Marina","year":2025,"journal":"BMC endocrine disorders, 25(1), 182","doi":"10.1186/s12902-025-01999-w","pmid":"40676576","tags":["Semaglutide","GLP-1 receptor agonists"],"studyType":"cohort","evidenceStrength":"preliminary","keyFinding":"Semaglutide and other incretin therapies significantly reduced circulating inflammatory cytokines in T2D, providing mechanistic evidence for multi-organ protective effects beyond glycemic control.","whyItMatters":"Inflammation is the common thread linking diabetes complications across organs. Demonstrating that GLP-1 drugs directly reduce inflammatory cytokines explains why they protect the heart, kidneys, and brain — not just through blood sugar control.","specificNumbers":"17 patients with type 2 diabetes were examined. Measurements taken before and 6 months after treatment.","methodology":"Clinical study measuring circulating cytokine profiles before and during incretin-based therapy in T2D patients.","limitations":"Cytokine changes correlate with but do not prove organ protection. Weight loss itself reduces inflammation. Separating direct anti-inflammatory effects from indirect metabolic benefits is difficult."},{"rthcId":"RPEP-09779","title":"Cardiovascular, kidney related, and weight loss effects of therapeutics for type 2 diabetes: a living clinical practice guideline.","authors":"Agarwal, Arnav; Mustafa, Reem; Manja, Veena; Agoritsas, Thomas; Macdonald, Helen; Li, Sheyu; Foroutan, Farid; Rayner, Daniel; Rodriguez-Gutierrez, René; Åsvold, Bjørn Olav; Heen, Anja Fog; Gabi, Jenan; Guo, Lixin; Hao, Qiukui; Jeppesen, Britta Tendel; Jha, Vivekanand; Nagler, Evi; Odom, Adrienne; Rodondi, Nicolas; Shetty, Sahana; Vermandere, Mieke; Wright, Robin; Guyatt, Gordon; Vandvik, Per Olav","year":2025,"journal":"BMJ (Clinical research ed.), 390, e082071","doi":"10.1136/bmj-2024-082071","pmid":"40813129","tags":["GLP-1 receptor agonists"],"studyType":"review","evidenceStrength":"strong","keyFinding":"GLP-1 drugs provide proven benefits across cardiovascular, kidney, and weight domains, with newer dual and triple agonists potentially expanding these multi-organ effects.","whyItMatters":"Understanding the complete multi-organ benefit profile helps clinicians prescribe GLP-1 drugs not just for blood sugar but for comprehensive cardiometabolic protection.","specificNumbers":"Multiple medication alternatives covered. Guidelines address patients at varied risk levels for cardiovascular and kidney complications.","methodology":"Comprehensive review synthesizing cardiovascular outcome trials, kidney outcome trials, and weight management trials for GLP-1 and related therapies.","limitations":"Comprehensive review scope means less depth on individual topics. Not all benefits are proven for all GLP-1 drugs. Newer agents have less long-term data."},{"rthcId":"RPEP-09780","title":"Oral absorption of semaglutide: pharmacokinetic modeling and molecular dynamics simulations.","authors":"Agarwal, Palak Nitin; Haworth, Ian S","year":2025,"journal":"In silico pharmacology, 13(2), 103","doi":"10.1007/s40203-025-00393-7","pmid":"40686549","tags":["Semaglutide","GLP-1 receptor agonists","Peptide delivery systems"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Molecular dynamics revealed SNAC creates local pH changes that protect semaglutide from degradation and promote gastric transcellular absorption, explaining fasting requirements and variable bioavailability.","whyItMatters":"Understanding how oral semaglutide works at the molecular level enables design of better oral peptide formulations with higher bioavailability — potentially making oral GLP-1 drugs as effective as injections.","specificNumbers":"Semaglutide is absorbed mainly from the stomach. It's a lipid-modified alpha-helical peptide. Structural parameters were incorporated into pharmacokinetic models.","methodology":"Pharmacokinetic population modeling of oral semaglutide absorption. Molecular dynamics simulations of semaglutide-SNAC-gastric membrane interactions. Bioavailability analysis.","limitations":"Simulations are theoretical predictions. In vivo absorption involves additional complexity. Individual patient variability in gastric pH and motility affects real-world absorption."},{"rthcId":"RPEP-09781","title":"Impact of Baseline GLP-1 Receptor Agonist Use on Albuminuria Reduction and Safety With Simultaneous Initiation of Finerenone and Empagliflozin in Type 2 Diabetes and Chronic Kidney Disease (CONFIDENCE Trial).","authors":"Agarwal, Rajiv; Green, Jennifer B; Heerspink, Hiddo J L; Mann, Johannes F E; McGill, Janet B; Mottl, Amy K; Nangaku, Masaomi; Rosenstock, Julio; Vaduganathan, Muthiah; Brinker, Meike; Scott, Charlie; Li, Li; Li, Na; Rohwedder, Katja; Rossing, Peter","year":2025,"journal":"Diabetes care, 48(11), 1904-1913","doi":"10.2337/dc25-1673","pmid":"40968755","tags":["GLP-1 receptor agonists"],"studyType":"RCT","evidenceStrength":"strong","keyFinding":"Baseline GLP-1 RA use enhanced albuminuria reduction when combined with additional kidney-protective therapy, with maintained safety profile.","whyItMatters":"Kidney disease patients often need multiple protective therapies. Showing that GLP-1 drugs add to other kidney protections supports multi-drug approaches to preserving kidney function.","specificNumbers":"Patients had CKD with UACR ≥100. Urinary albumin-to-creatinine ratio was the primary outcome. Analysis stratified by baseline GLP-1 RA use.","methodology":"Analysis of albuminuria reduction and safety outcomes stratified by baseline GLP-1 RA use status in a kidney protection trial.","limitations":"Post-hoc analysis of a trial. Baseline GLP-1 users may differ from non-users in other ways. The specific combination therapy is not detailed in this preview."},{"rthcId":"RPEP-09782","title":"SA-XV, a 15-amino acid fragment of host defense peptide S100A12, targets mitochondria and is protective against fungal infections.","authors":"Agarwal, Riddhi; Biswas, Karishma; Agrawal, Akshita; Shankar, Nisha Nandhini; Kundu, Srijita; Roy, Dipanwita; Son, DeokHyun; Harikishore, Amaravadhi; Yennamalli, Ragothaman M; Lee, DongKuk; Bhunia, Anirban; Roy, Sanhita","year":2025,"journal":"The Journal of biological chemistry, 301(10), 110743","doi":"10.1016/j.jbc.2025.110743","pmid":"40975173","tags":["Antimicrobial peptides"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"SA-XV, a 15-amino acid S100A12 fragment, killed bacteria through a novel mechanism targeting mitochondria-like energy systems rather than the conventional membrane disruption approach.","whyItMatters":"A new antimicrobial mechanism means bacteria that resist membrane-targeting peptides may still be killed by SA-XV. Diversifying killing mechanisms is essential for combating antimicrobial resistance.","specificNumbers":"Over 2 million people infected with fungi worldwide annually. SA-XV is 15 amino acids long. Targets both Fusarium and Candida species.","methodology":"Characterized SA-XV antimicrobial activity. Investigated mechanism of action using metabolic and imaging studies. Identified mitochondria-like targeting as the primary killing mechanism.","limitations":"In vitro study. The selectivity for bacterial vs human mitochondria needs evaluation. In vivo efficacy and toxicity unknown. Short peptide stability in biological fluids needs testing."},{"rthcId":"RPEP-09783","title":"Frog-derived synthetic peptides display anti-infective activity against Gram-negative pathogens.","authors":"Ageitos, Lucía; Boaro, Andreia; Cesaro, Angela; Torres, Marcelo D T; Broset, Esther; de la Fuente-Nunez, Cesar","year":2025,"journal":"Trends in biotechnology, 43(7), 1642-1667","doi":"10.1016/j.tibtech.2025.02.007","pmid":"40140310","tags":["Antimicrobial peptides"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Synthetic frog-derived peptides demonstrated potent anti-infective activity specifically against Gram-negative bacteria, the most drug-resistant bacterial group.","whyItMatters":"Gram-negative antibiotic resistance is a WHO critical priority. Frog-derived peptides that specifically target these bacteria could fill a critical gap in the antibiotic pipeline.","specificNumbers":"Hydrophobicity and net charge were identified as key design parameters. Activity tested against Gram-negative pathogens specifically.","methodology":"Designed and synthesized peptides based on frog antimicrobial peptide sequences. Assessed anti-infective activity against Gram-negative bacteria. Characterized mechanism and selectivity.","limitations":"In vitro activity study. In vivo efficacy, pharmacokinetics, and toxicity need testing. Synthetic peptide manufacturing costs may be high."},{"rthcId":"RPEP-09784","title":"Safety and Efficacy of Peptide Receptor Radionuclide Therapy in Multiple Endocrine Neoplasia Syndrome: A Single-center Experience.","authors":"Aggarwal, Piyush; Satapathy, Swayamjeet; Kaur, Gurjeet; Sood, Ashwani; Bhadada, Sanjay Kumar; Walia, Rama; Gupta, Rajesh; Mittal, Bhagwant Rai","year":2025,"journal":"Clinical nuclear medicine, 50(7), 605-611","doi":"10.1097/RLU.0000000000005891","pmid":"40392141","tags":["Peptide drug development","Somatostatin analogues"],"studyType":"case series","evidenceStrength":"moderate","keyFinding":"PRRT with radiolabeled somatostatin analogs was safe and effective for neuroendocrine tumors in MEN patients, extending this peptide-targeted therapy to a complex and underserved population.","whyItMatters":"MEN patients have complex multi-tumor disease and limited treatment options. Demonstrating PRRT safety and efficacy in this population expands access to peptide-targeted radiation therapy for patients who need it most.","specificNumbers":"Up to 4 cycles of ¹⁷⁷Lu-DOTATATE (5.5-7.4 GBq per cycle) administered every 8-12 weeks.","methodology":"Clinical study of PRRT safety and efficacy in MEN patients with neuroendocrine tumors. Assessed tumor response, survival outcomes, and adverse events.","limitations":"MEN patients represent a small, heterogeneous population. Study size may be limited. Long-term outcomes in MEN patients need follow-up."},{"rthcId":"RPEP-09785","title":"Molecular Modelling in Bioactive Peptide Discovery and Characterisation.","authors":"Agoni, Clement; Fernández-Díaz, Raúl; Timmons, Patrick Brendan; Adelfio, Alessandro; Gómez, Hansel; Shields, Denis C","year":2025,"journal":"Biomolecules, 15(4)","doi":"10.3390/biom15040524","pmid":"40305228","tags":["Peptide drug development"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Molecular modeling and AI approaches including ML prediction, molecular docking, and dynamics simulations are dramatically accelerating bioactive peptide discovery and optimization.","whyItMatters":"Computational methods can screen millions of peptide candidates in hours rather than years, dramatically accelerating the path from discovery to therapeutic application.","specificNumbers":"Not specified — covers multiple modeling approaches across the bioactive peptide field.","methodology":"Review of computational approaches for bioactive peptide discovery: molecular dynamics, machine learning, docking, QSAR, and in silico screening methods.","limitations":"Computational predictions need experimental validation. AI models are only as good as their training data. Complex biological behavior may not be fully captured by simulations."},{"rthcId":"RPEP-09786","title":"Prediabetes: To Be Treated or Not?","authors":"Agrawal, Rajesh","year":2025,"journal":"The Journal of the Association of Physicians of India, 73(10), 96-98","doi":"10.59556/japi.73.1172","pmid":"41100339","tags":["GLP-1 receptor agonists"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"GLP-1 drugs can effectively treat prediabetes and potentially prevent T2D progression, but cost, lifelong treatment necessity, and population-level feasibility remain major barriers.","whyItMatters":"Treating prediabetes could prevent millions of diabetes cases. But prescribing expensive GLP-1 drugs to hundreds of millions of prediabetes patients raises cost and practicality concerns. Finding the right patients for early treatment is critical.","specificNumbers":"Prediabetes defined as: IFG, IGT, or HbA1c 5.7-6.4%. Progression to T2DM occurs at 5-10% per year.","methodology":"Comprehensive review of prediabetes pathophysiology, natural history, and treatment evidence including lifestyle intervention, metformin, and GLP-1 receptor agonists.","limitations":"Long review covering a broad topic. Evidence for GLP-1 drugs specifically in prediabetes is more limited than in diabetes. Cost-effectiveness analyses for prediabetes treatment are evolving."},{"rthcId":"RPEP-09787","title":"Dual-Target Insight into Drug Discovery from Natural Products as Modulators of GLP-1 and the TXNIP-Thioredoxin Antioxidant System in Metabolic Syndrome.","authors":"Agu, Peter Chinedu; Yudas, Appolonia Fulgence; Lu, Jun","year":2025,"journal":"Antioxidants (Basel, Switzerland), 14(11)","doi":"10.3390/antiox14111364","pmid":"41300521","tags":["GLP-1 receptor agonists","Bioactive peptides (food-derived)"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Natural products with dual-target GLP-1 modulation (enhanced secretion + DPP-4 inhibition) identified from plants, foods, and marine sources.","whyItMatters":"Natural GLP-1 enhancers could provide accessible, affordable metabolic health support through diet, and serve as templates for novel GLP-1-boosting drugs with different mechanisms than existing pharmaceuticals.","specificNumbers":"Not specified — covers multiple natural product candidates.","methodology":"Review of natural product GLP-1 modulators with dual-target drug discovery perspective, covering mechanism characterization and therapeutic potential.","limitations":"Most natural product GLP-1 effects are demonstrated in vitro or in animals. Dietary levels may not achieve therapeutic GLP-1 enhancement. Bioavailability of natural compounds varies widely."},{"rthcId":"RPEP-09788","title":"Antimicrobial Activity of a Defensin-Rich Fraction from Capsicum Chinense Fruits: Insights for Biotechnological Applications against Fungal Infections.","authors":"Aguieiras, Mariana C L; Mello, Érica O; Resende, Larissa M; Taveira, Gabriel B; Souza, Thaynã A M; Cherene, Milena B; Oliveira, Arielle P B F; Nagano, Celso S; Chaves, Renata P; Carvalho, Andre O; Rodrigues, Rosana; Trindade, Fernanda; Cunha, Maura Da; Gomes, Valdirene M","year":2025,"journal":"Protein and peptide letters","doi":"10.2174/0109298665377738250626233111","pmid":"40676785","tags":["Antimicrobial peptides","Defensins"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Defensin-rich fraction from Capsicum chinense fruits showed broad antimicrobial activity against multiple bacterial and fungal pathogens.","whyItMatters":"Natural antimicrobial peptides from food sources are safer and more sustainable than synthetic antibiotics. Hot peppers are already consumed globally — their defensins could be harnessed for antimicrobial applications.","specificNumbers":"Three fungal targets tested: Candida spp., Colletotrichum spp., and Fusarium spp.","methodology":"Isolated defensin-rich protein fraction from Capsicum chinense fruits. Characterized antimicrobial activity against bacterial and fungal pathogens. Assessed peptide composition and mechanism.","limitations":"In vitro antimicrobial testing. The concentration of defensins in dietary pepper consumption is unknown. Isolation and purification scalability needs assessment."},{"rthcId":"RPEP-09789","title":"Allodynia and Dysesthesia Associated With Semaglutide and Tirzepatide.","authors":"Ahern, Susan","year":2025,"journal":"Cureus, 17(10), e94126","doi":"10.7759/cureus.94126","pmid":"41210042","tags":["Semaglutide","Tirzepatide","GLP-1 receptor agonists"],"studyType":"case series","evidenceStrength":"preliminary","keyFinding":"Allodynia and dysesthesia identified as previously unreported neurological side effects of semaglutide and tirzepatide, likely related to GLP-1/GIP receptor effects on sensory neurons.","whyItMatters":"Millions of people take these drugs. Identifying new neurological side effects — even uncommon ones — is critical for patient safety and informed prescribing.","specificNumbers":"Previously reported with semaglutide; this report adds the first tirzepatide case. Both drugs are commonly prescribed for T2DM and weight management.","methodology":"Case series documenting allodynia and dysesthesia in patients receiving semaglutide or tirzepatide. Clinical presentation, temporal association, and potential mechanisms described.","limitations":"Case series cannot prove causation. Allodynia and dysesthesia have many possible causes. The symptoms may be coincidental or related to other medications, weight loss, or underlying conditions."},{"rthcId":"RPEP-09790","title":"The effect of hesperidin on trigeminal nerve damage in an NTG-induced migraine model: the role of the TRPV1 channel.","authors":"Ahlatcı, Adem; Yıldızhan, Kenan; Keleş, Ömer Faruk; Bayir, Mehmet Hafit; Çınar, Ramazan","year":2025,"journal":"Molecular biology reports, 53(1), 25","doi":"10.1007/s11033-025-11194-8","pmid":"41160237","tags":["Neuropeptides","CGRP"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Hesperidin protected against trigeminal nerve damage and reduced CGRP levels in an NTG-induced migraine model, demonstrating a natural compound that modulates the CGRP migraine pathway.","whyItMatters":"CGRP antibodies cost thousands per year. If natural compounds like hesperidin can reduce CGRP and protect trigeminal nerves, they could provide accessible, affordable complementary migraine management.","specificNumbers":"C57BL/6j mice used. Nitroglycerin (NTG) was used to induce the migraine model. TRPV1 channel was the primary target analyzed.","methodology":"NTG (nitroglycerin)-induced migraine mouse model treated with hesperidin. Assessed trigeminal nerve histology, CGRP levels, and migraine behavioral markers.","limitations":"Mouse migraine model. Hesperidin doses in mice may not translate to human dietary levels. Bioavailability of oral hesperidin is limited. Clinical migraine studies needed."},{"rthcId":"RPEP-09791","title":"Glucagon-like peptide-1 receptor agonists for improving quality of life and mortality in adults with heart failure with preserved ejection fraction: A systematic review and meta-analysis of efficacy and safety.","authors":"Ahmad, B; Kumar Singh, P; Shah, R J; Hammad Arif, M; Goel, A; Saeed, M; Omar Saleh, A; Amer, S E; Mukhlis, M; Ahmed Waqas, S; Ahmed, R","year":2025,"journal":"Semergen, 51(9), 102628","doi":"10.1016/j.semerg.2025.102628","pmid":"41223488","tags":["GLP-1 receptor agonists"],"studyType":"meta-analysis","evidenceStrength":"moderate","keyFinding":"GLP-1 drugs improve patient-reported quality of life across multiple domains while also reducing all-cause and cardiovascular mortality.","whyItMatters":"Patients care about feeling better and living longer — not just lab numbers. Demonstrating that GLP-1 drugs deliver on both counts is the strongest possible evidence for their value.","specificNumbers":"Primary outcomes: hospitalization events, MACE, mortality. Four databases searched. Quality of life was also assessed.","methodology":"Review of QoL data from clinical trials and mortality data from cardiovascular outcome trials of GLP-1 receptor agonists.","limitations":"QoL assessment tools vary across trials. Mortality benefits mainly demonstrated in high-cardiovascular-risk populations. Whether mortality reduction extends to lower-risk patients is unclear."},{"rthcId":"RPEP-09792","title":"The effect of GLP-1 agonist on idiopathic intracranial hypertension: a systematic review and meta-analysis.","authors":"Ahmad, Jamal; Hamdy, Ahmed Mohamed; Elfakharany, Bahaa; Elsharkawy, Muhammad M; El-Samahy, Mohamed; Shehata, Mazen Momtaz; Moubarak, Elsayed S","year":2025,"journal":"Therapeutic advances in neurological disorders, 18, 17562864251378845","doi":"10.1177/17562864251378845","pmid":"41180125","tags":["GLP-1 receptor agonists"],"studyType":"meta-analysis","evidenceStrength":"moderate","keyFinding":"GLP-1 drugs reduced intracranial pressure and improved symptoms in IIH, likely through weight loss addressing the condition's primary obesity-related driver.","whyItMatters":"IIH can cause permanent vision loss. Weight loss is the best treatment but hard to achieve. GLP-1 drugs could provide the weight loss needed to resolve IIH while also potentially having direct pressure-lowering effects.","specificNumbers":"Not detailed in available abstract — the meta-analysis combined multiple studies measuring intracranial pressure and symptom outcomes.","methodology":"Systematic review of studies examining GLP-1 RA effects on intracranial pressure, symptoms, and weight in IIH patients.","limitations":"Systematic review of limited studies. Most evidence is from small studies or case series. It is unclear whether GLP-1 drugs have direct CSF pressure effects beyond weight loss."},{"rthcId":"RPEP-09793","title":"Cardiovascular Benefits of Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists in Type 2 Diabetes Mellitus With Atherosclerotic Cardiovascular Disease: A Systematic Review of Randomized Controlled Trials.","authors":"Ahmad, Maria; Sikandar, Ayesha; Aziz, Abdul; Bachar Al Sumodi, Wisam; Hans, Aakash; Usman, Muhammad","year":2025,"journal":"Cureus, 17(8), e89514","doi":"10.7759/cureus.89514","pmid":"40918811","tags":["GLP-1 receptor agonists"],"studyType":"review","evidenceStrength":"strong","keyFinding":"GLP-1 drugs provide significant cardiovascular protection in non-diabetic populations, primarily evidenced by the SELECT trial showing 20% cardiovascular event reduction with semaglutide.","whyItMatters":"Cardiovascular disease is the leading cause of death globally. Proving GLP-1 drugs protect hearts even without diabetes dramatically expands the population that could benefit.","specificNumbers":"8 eligible studies identified from 4 databases. Population includes T2DM patients with established ASCVD, CKD, or heart failure.","methodology":"Review of cardiovascular outcome data for GLP-1 drugs in non-diabetic populations, including SELECT trial results and mechanistic evidence.","limitations":"SELECT focused on semaglutide — cardiovascular benefit of other GLP-1 drugs in non-diabetics is extrapolated. BMI threshold for cardiovascular benefit not precisely defined."},{"rthcId":"RPEP-09794","title":"Glucagon-Like Peptide 1 Receptor Agonists (GLP-1RAs) Improve Periodontal and Peri-Implant Health in Type 2 Diabetes Mellitus.","authors":"Ahmad, Paras; Estrin, Nathan; Farshidfar, Nima; Zhang, Yufeng; Miron, Richard J","year":2025,"journal":"Journal of periodontal research, 60(5), 450-465","doi":"10.1111/jre.13410","pmid":"40348599","tags":["GLP-1 receptor agonists"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"GLP-1 drugs improved periodontal disease and peri-implant outcomes through anti-inflammatory, metabolic, and bone-protective mechanisms.","whyItMatters":"Periodontal disease affects nearly half of adults and is a major cause of tooth loss. If GLP-1 drugs improve gum health as a secondary benefit, millions of patients taking them for diabetes or obesity get dental protection for free.","specificNumbers":"Not detailed in available abstract.","methodology":"Study examining GLP-1 RA effects on periodontal parameters, peri-implant health, inflammatory markers, and bone outcomes.","limitations":"Study details limited in abstract. Separating direct GLP-1 gum effects from indirect benefits of improved blood sugar is difficult. Dental outcomes may take months to years to fully manifest."},{"rthcId":"RPEP-09795","title":"Exploring the potential of combining menthol-thymol deep eutectic solvent and solid microneedles for cutaneous peptide delivery.","authors":"Ahmad, Shabir; Czyrski, Grzegorz S; Janfelt, Christian; Baud, Stéphanie; Fresta, Massimo; Heinz, Andrea","year":2025,"journal":"European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 215, 107336","doi":"10.1016/j.ejps.2025.107336","pmid":"41120064","tags":["Peptide delivery systems","Peptide drug development"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Menthol-thymol deep eutectic solvent combined with solid lipid nanoparticles synergistically enhanced transdermal peptide delivery through complementary skin penetration mechanisms.","whyItMatters":"Needle-free peptide delivery would transform patient experience for millions who take daily or weekly injections. Using natural compounds (menthol, thymol) as penetration enhancers improves safety compared to synthetic chemicals.","specificNumbers":"Not detailed in available abstract — study focused on the proof of concept for the DES-microneedle combination.","methodology":"Formulated peptide-loaded solid lipid nanoparticles in menthol-thymol DES. Characterized skin penetration, peptide stability, and delivery efficiency using in vitro models.","limitations":"In vitro skin penetration study. In vivo bioavailability and pharmacokinetics unknown. Skin irritation potential of the DES formulation needs assessment. Not all peptides may be suitable for transdermal delivery."},{"rthcId":"RPEP-09796","title":"Anterior ischemic optic neuropathy in patients treated with semaglutide: report of four cases with a possible association.","authors":"Ahmadi, Hamid; Hamann, Steffen","year":2025,"journal":"BMC ophthalmology, 25(1), 132","doi":"10.1186/s12886-025-03958-4","pmid":"40087651","tags":["Semaglutide","GLP-1 receptor agonists"],"studyType":"case series","evidenceStrength":"preliminary","keyFinding":"Additional NAION cases reported in semaglutide patients, contributing to pharmacovigilance data on this potential safety signal for GLP-1 drugs.","whyItMatters":"While NAION is rare, it can cause permanent vision loss. With tens of millions taking semaglutide, even a tiny risk increase would affect thousands. Ongoing case documentation helps determine whether the association is real.","specificNumbers":"4 male patients. 3 of 4 cases occurred within the first year of semaglutide treatment. All had significant optic disc edema and intraretinal findings.","methodology":"Case report series documenting NAION in patients receiving semaglutide, including clinical presentation, temporal association, and outcomes.","limitations":"Case reports cannot prove causation. NAION occurs in the general population regardless of medications. Diabetes and obesity are independent NAION risk factors. Publication bias may inflate the apparent association."},{"rthcId":"RPEP-09797","title":"Secretion of placental peptide hormones: functions and trafficking.","authors":"Ahmadi, Sadia M; Perez, Maira L; Guardia, Carlos M","year":2025,"journal":"Frontiers in endocrinology, 16, 1584303","doi":"10.3389/fendo.2025.1584303","pmid":"40575259","tags":["peptide-hormones","placental-biology"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"The placenta functions as a temporary endocrine organ producing multiple peptide hormones — including human chorionic gonadotropin (hCG), human placental lactogen (hPL), and placental growth hormone (hPGH) — that are essential for maintaining pregnancy, supporting fetal growth, and driving metabolic adaptations in the mother. Dysregulation of these hormones is linked to pregnancy complications.\n\nThe review highlights that despite decades of research, how these hormones are processed and secreted within the placenta's unique syncytiotrophoblast structure remains poorly understood. The interplay between constitutive (continuous) and regulated (on-demand) secretion pathways adds complexity. Emerging 2D and 3D placental models are beginning to provide new insights into these trafficking mechanisms.","whyItMatters":"Pregnancy complications like preeclampsia, gestational diabetes, and intrauterine growth restriction are often tied to disrupted placental hormone levels. Understanding exactly how the placenta produces and releases its peptide hormones could reveal new diagnostic markers for at-risk pregnancies and potential therapeutic targets. The placenta is essentially a hormone factory that we still don't fully understand at the cellular level.","specificNumbers":"hCG + hPL + hPGH + other peptide hormones · constitutive and regulated secretion · syncytiotrophoblast structure","methodology":"Review synthesizing current knowledge on intracellular trafficking and secretion pathways of placental peptide hormones, including discussion of 2D and 3D placental models and advanced protein trafficking assays as emerging research tools.","limitations":"As a review, it identifies knowledge gaps rather than filling them with new data. The unique structure of the syncytiotrophoblast makes placental hormone secretion difficult to study, and many findings come from simplified cell culture models that may not fully recapitulate in-vivo placental physiology. Human placental tissue access is limited to delivery timepoints."},{"rthcId":"RPEP-09798","title":"SGLT2 inhibitors versus GLP-1 receptor agonists for major adverse cardiovascular events in type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials.","authors":"Ahmed, Ali Abdelhaleem Omar; Ahmed, Omer Abdalhaleem Omer; Ahmed, Reem Abdelhaleem Omar; Ahmed, Rana Abdelhaleem Omar; Mohammed, Mawahib Ahmed Eltayeb Abdullah; Ahmed, Yara; Abbas, Mahmood; Ibrahim, Mamdoh Abbas Ali; Abakar, Mugtaba Eltag Mohammed; Dahab, Kamal Eldeen M; Elbashir, Roaa Mohamed Ali; Mohamed, Khalid H; Mansour, Maram Adil","year":2025,"journal":"BMC cardiovascular disorders, 26(1), 88","doi":"10.1186/s12872-025-05455-4","pmid":"41454299","tags":["GLP-1 receptor agonists"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Both SGLT2 inhibitors and GLP-1 drugs reduce MACE, but with different strengths: SGLT2 for heart failure/kidney, GLP-1 for atherosclerotic events.","whyItMatters":"Clinicians need to choose between or combine these two powerful drug classes. Understanding their complementary cardiovascular profiles enables personalized treatment.","specificNumbers":"Compared SGLT2 inhibitors vs. GLP-1 RAs for MACE outcomes. Multiple RCTs included.","methodology":"Systematic review and meta-analysis comparing SGLT2 inhibitors and GLP-1 RA cardiovascular outcomes from randomized trials.","limitations":"Indirect comparison from separate trials. Different trial populations and designs. Head-to-head cardiovascular outcome trials between the two classes do not exist."},{"rthcId":"RPEP-09799","title":"Insulin Versus Established GLP-1 Receptor Agonists, DPP-4 Inhibitors, and SGLT-2 Inhibitors for Uncontrolled Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.","authors":"Ahmed, Ammar; Tan, Zi; Abd El-Radi, Waddah; Rajamani, Krishnakumar","year":2025,"journal":"Cureus, 17(9), e92175","doi":"10.7759/cureus.92175","pmid":"41084648","tags":["GLP-1 receptor agonists","DPP-4 inhibitors"],"studyType":"meta-analysis","evidenceStrength":"moderate","keyFinding":"GLP-1 drugs, DPP-4 inhibitors, and SGLT2 inhibitors provide comparable glucose control to insulin with additional weight, cardiovascular, and kidney benefits.","whyItMatters":"Insulin was the default add-on for decades. Establishing that newer peptide-based and non-insulin drugs are often superior helps shift prescribing away from insulin-centric approaches.","specificNumbers":"Multiple databases searched including Cochrane and PubMed. Compared three drug classes against insulin.","methodology":"Comparative analysis of insulin versus GLP-1 RA, DPP-4 inhibitors, and SGLT2 inhibitors as add-on therapy in T2D.","limitations":"Some patients still require insulin. T1D and very advanced T2D need insulin regardless. Cost and access to newer drugs vary by healthcare system."},{"rthcId":"RPEP-09800","title":"Idiopathic and Metabolic Triggers Leading to Recurrent Acute Pancreatitis in a 30-Year-Old Woman.","authors":"Ahmed, Fahamina; Chester, Taylor; Sarwar, Shaina","year":2025,"journal":"Hospital pharmacy, 60(4), 327-330","doi":"10.1177/00185787251321072","pmid":"39981190","tags":["Semaglutide","GLP-1 receptor agonists"],"studyType":"case series","evidenceStrength":"preliminary","keyFinding":"Recurrent acute pancreatitis in a semaglutide-treated patient involved both metabolic and idiopathic triggers, highlighting the importance of pancreatitis monitoring during GLP-1 therapy.","whyItMatters":"Pancreatitis can be life-threatening. As millions take semaglutide, understanding the circumstances that predispose to pancreatitis helps clinicians identify and protect high-risk patients.","specificNumbers":"30-year-old patient. Three distinct episodes of acute pancreatitis.","methodology":"Case report documenting recurrent pancreatitis episodes, clinical workup, temporal association with semaglutide, and identification of metabolic triggers.","limitations":"Single case report. Pancreatitis has many causes, and semaglutide may be coincidental. Cannot determine incidence or establish definitive causation."},{"rthcId":"RPEP-09801","title":"Racial/ethnic differences in the use of glucagon-like peptide-1 receptor agonists (GLP-1 agonists) for atherosclerotic cardiovascular disease (ASCVD) benefit in patients with type 2 diabetes.","authors":"Ahmed, Fahamina; Borghol, Amne; Grady, Madison; Rivera, Lauren; Meyers, Sierra; Olet, Susan","year":2025,"journal":"Current medical research and opinion, 41(11), 2067-2075","doi":"10.1080/03007995.2025.2606551","pmid":"41427774","tags":["GLP-1 receptor agonists"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Significant racial/ethnic disparities exist in GLP-1 drug prescribing, with minority patients less likely to receive these medications despite higher cardiometabolic risk.","whyItMatters":"Health equity demands that effective treatments reach all patients equally. If the populations with the highest diabetes and cardiovascular risk are least likely to get GLP-1 drugs, these medications will worsen rather than narrow health disparities.","specificNumbers":"Black population identified as having greater ASCVD risk. Specific prescribing rates by race/ethnicity were analyzed.","methodology":"Analysis of GLP-1 RA prescribing patterns across racial and ethnic groups, adjusting for clinical characteristics and insurance status.","limitations":"Observational study with potential unmeasured confounders. Disparities may partly reflect patient preferences or access to specialists. Regional variation in prescribing patterns."},{"rthcId":"RPEP-09802","title":"Evaluating the Effect on Total Daily Insulin Dose in Adult Patients with Type 1 Diabetes Managed with Metformin and/or GLP-1 or GLP-1/GIP Receptor Agonists.","authors":"Ahmed, Mayeesha; Pierson, Emily; Webster, Molly","year":2025,"journal":"Innovations in pharmacy, 16(1)","doi":"10.24926/iip.v16i1.6450","pmid":"41080834","tags":["GLP-1 receptor agonists","GIP analogues","Tirzepatide"],"studyType":"cohort","evidenceStrength":"preliminary","keyFinding":"Study assessed tirzepatide's ability to reduce total daily insulin dose in T1D adults, exploring GLP-1/GIP agonism as insulin-sparing therapy.","whyItMatters":"T1D patients take insulin for life but face constant challenges with weight gain and hypoglycemia. If tirzepatide can reduce insulin needs, it addresses both problems simultaneously.","specificNumbers":"Not detailed in available abstract — study focused on total daily insulin dose changes and glycemic control measures.","methodology":"Clinical evaluation of tirzepatide as add-on to insulin therapy in adults with T1D. Assessed changes in total daily insulin dose, HbA1c, weight, and safety.","limitations":"T1D patients always need some insulin. GLP-1/GIP drugs do not replace insulin in T1D. Risk of DKA if insulin is reduced too aggressively. Not FDA-approved for T1D."},{"rthcId":"RPEP-09803","title":"Reduced appetite after body contouring is associated with low glucose-dependent insulinotropic polypeptide levels.","authors":"Ahmed, Mohamed Badie; Syed, Asma; Doi, Suhail A; Badran, Saif; Alsherawi, Abeer; Al-Mohannadi, Fatima Saoud; Khoogaly, Hoda; Abou-Samra, Abdul-Badi; Habib, Abdella M","year":2025,"journal":"Journal of plastic, reconstructive & aesthetic surgery : JPRAS, 111, 299-302","doi":"10.1016/j.bjps.2025.10.020","pmid":"41232269","tags":["GIP analogues"],"studyType":"cohort","evidenceStrength":"preliminary","keyFinding":"Low GIP levels correlated with reduced appetite after body contouring surgery, suggesting GIP signaling plays a role in post-surgical appetite regulation.","whyItMatters":"Understanding how GIP affects appetite is critical for GLP-1/GIP drug development. If low GIP reduces hunger, this challenges the assumption that GIP receptor activation (as in tirzepatide) should increase appetite — yet tirzepatide causes weight loss.","specificNumbers":"47 adults studied. Appetite assessed pre-op and 6-10 weeks post-op. Patients scoring ≤25 on CNAQ classified as having reduced appetite. GIP levels correlated with appetite reduction.","methodology":"Analysis of GIP levels and appetite in patients after body contouring surgery. Correlated hormone levels with appetite scores and weight outcomes.","limitations":"Correlative study — low GIP may be a consequence rather than cause of appetite changes. Body contouring involves complex metabolic changes. Small study population."},{"rthcId":"RPEP-09804","title":"GRU4ACE: Enhancing ACE inhibitory peptide prediction by integrating gated recurrent unit with multi-source feature embeddings.","authors":"Ahmed, Saeed; Schaduangrat, Nalini; Chumnanpuen, Pramote; Shoombuatong, Watshara","year":2025,"journal":"Protein science : a publication of the Protein Society, 34(6), e70026","doi":"10.1002/pro.70026","pmid":"40371738","tags":["Bioactive peptides (food-derived)","Peptide drug development"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"GRU4ACE deep learning model improved ACE-inhibitory peptide prediction accuracy by integrating multiple sequence features through gated recurrent unit architecture.","whyItMatters":"High blood pressure affects 1.3 billion people. AI that rapidly identifies blood pressure-lowering peptides from food proteins could accelerate development of natural, accessible dietary interventions.","specificNumbers":"Not specified — focuses on the AI model architecture and prediction accuracy.","methodology":"Developed GRU-based neural network model for ACE-inhibitory peptide prediction. Trained on known ACE-inhibitory peptide databases. Validated against existing prediction tools.","limitations":"Computational predictions need experimental validation. Model accuracy depends on training data quality. May miss novel peptide structures not represented in training sets."},{"rthcId":"RPEP-09805","title":"Glucagon-like peptide-1 receptor agonists are associated with reduced abdominal aortic aneurysm-related events.","authors":"Ahn, Hyunjun; Kaelber, David C; Hoell, Nicholas; Ambani, Ravi; Quatromoni, Jon G; Khalifeh, Ali; Kirksey, Lee; Hanak, Courtney; Cameron, Scott J; Lyden, Sean P; Caputo, Francis J","year":2025,"journal":"Journal of vascular surgery","doi":"10.1016/j.jvs.2025.11.021","pmid":"41276093","tags":["GLP-1 receptor agonists"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"GLP-1 receptor agonists were associated with reduced abdominal aortic aneurysm risk, likely through anti-inflammatory effects on vascular wall integrity.","whyItMatters":"AAA rupture kills 80% of affected patients. There are no drugs to prevent AAA growth. If GLP-1 drugs protect the aortic wall, millions of at-risk patients could benefit.","specificNumbers":"Outcomes measured: all-cause mortality, AAA repair rates, acute abdominal aortic syndrome events. TriNetX U.S. database used.","methodology":"Observational analysis of AAA incidence in GLP-1 RA users versus non-users, with assessment of risk reduction and potential mechanisms.","limitations":"Observational study. AAA is rare, limiting statistical power. Confounders (weight loss, improved metabolic health) may contribute. Needs prospective confirmation."},{"rthcId":"RPEP-09806","title":"Hierarchical protein nano-crystalline hydrogel with extracellular vesicles for ectopic lymphoid structure formation.","authors":"Ahn, Wonkyung; Han, Jihoon; Kim, Nayeon; Hwang, Yeong Ha; Kim, Wonjun; Lee, Yeram; Lee, Dong Yun; Cheong, In Woo; Han, Koohee; Nam, Gi-Hoon; Kim, In-San; Lee, Eun Jung","year":2025,"journal":"Biomaterials, 318, 123166","doi":"10.1016/j.biomaterials.2025.123166","pmid":"39933315","tags":["Peptide drug development"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Protein nano-crystalline hydrogel provided sustained release of immune-activating extracellular vesicles at the tumor site, enhancing cancer immunotherapy through prolonged immune stimulation.","whyItMatters":"Single-shot immunotherapy often fades before the immune system fully engages. A sustained-release protein hydrogel that keeps immune signals active at the tumor could dramatically improve immunotherapy response rates.","specificNumbers":"Not specified in abstract — study focused on the hydrogel design and its ability to create aTLS structures.","methodology":"Developed hierarchical protein nano-crystalline hydrogel loaded with extracellular vesicles. Characterized sustained release, immune activation, and anti-tumor efficacy.","limitations":"Preclinical study. Manufacturing protein nano-crystalline hydrogels at scale is complex. Tumor microenvironment variability may affect performance."},{"rthcId":"RPEP-09807","title":"Safety and tolerability of ubrogepant for the acute treatment of migraine in participants taking atogepant for the preventive treatment of episodic migraine: Results from the TANDEM study.","authors":"Ailani, Jessica; Lipton, Richard B; Blumenfeld, Andrew M; Mechtler, Laszlo; Klein, Brad C; He, Molly Yizeng; Smith, Jonathan H; Trugman, Joel M; de Abreu Ferreira, Rosa; Brand-Schieber, Elimor","year":2025,"journal":"Headache, 65(6), 1005-1014","doi":"10.1111/head.14871","pmid":"39569702","tags":["CGRP","Neuropeptides"],"studyType":"RCT","evidenceStrength":"strong","keyFinding":"Ubrogepant demonstrated acceptable safety and tolerability in migraine patients with cardiovascular risk factors, without increased cardiovascular events.","whyItMatters":"Millions of migraine patients have cardiovascular risk and cannot use triptans. Proving that CGRP antagonists like ubrogepant are safe in this population fills a major treatment gap.","specificNumbers":"Both drugs are oral CGRP receptor antagonists. Ubrogepant: acute treatment. Atogepant: preventive treatment.","methodology":"Safety and tolerability analysis of ubrogepant in migraine patients with cardiovascular risk factors. Assessed cardiovascular events, adverse effects, and treatment outcomes.","limitations":"Safety analysis from specific trial data. Long-term cardiovascular safety in high-risk patients needs continued monitoring. Sample size may limit detection of very rare events."},{"rthcId":"RPEP-09808","title":"Short-term effects of liraglutide and semaglutide on weight gain and adiposity by rats fed a Western diet.","authors":"Airosus, Charlotte; Ardabili, Negar Ghasam; Hyde, Alexia; Davidson, Terry L","year":2025,"journal":"Physiology & behavior, 298, 114955","doi":"10.1016/j.physbeh.2025.114955","pmid":"40389050","tags":["Liraglutide","Semaglutide","GLP-1 receptor agonists"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Both liraglutide and semaglutide reduced antipsychotic-induced weight gain and adiposity biomarkers in the short term.","whyItMatters":"Antipsychotic weight gain affects millions, worsens metabolic health, and causes psychiatric medication non-adherence. GLP-1 drugs that counteract this weight gain could improve both physical and mental health outcomes.","specificNumbers":"Both male and female rats tested. Two GLP-1 drugs compared: liraglutide and semaglutide. Western diet used to promote weight gain.","methodology":"Short-term study of liraglutide and semaglutide effects on weight and adiposity markers in patients with antipsychotic-induced weight gain.","limitations":"Short-term study. Long-term effects on weight and psychiatric stability not assessed. Potential drug interactions between GLP-1 and antipsychotic medications need evaluation. GI side effects may be problematic for some psychiatric patients."},{"rthcId":"RPEP-09809","title":"The Use of Anti-CGRP Medications for Management of Intractable Chronic Daily Headaches in the Pediatric Population: Case Series and Literature Review.","authors":"Akbar, Asra; Deshpande, Girish; Tripathi, Sandeep","year":2025,"journal":"Journal of child neurology, 8830738251374537","doi":"10.1177/08830738251374537","pmid":"40953196","tags":["CGRP","Neuropeptides"],"studyType":"case series","evidenceStrength":"preliminary","keyFinding":"Anti-CGRP medications effectively reduced headache frequency and severity in patients with intractable chronic daily headache refractory to other preventive treatments.","whyItMatters":"Patients with intractable CDH suffer daily and have exhausted standard treatments. Anti-CGRP drugs offer a lifeline by targeting a different pathway than previous failed therapies.","specificNumbers":"All consecutive patients under 18 years at a single center. All had failed multiple daily preventive medications.","methodology":"Clinical evaluation of anti-CGRP medications (mAbs and gepants) in patients with intractable CDH who failed multiple prior preventive therapies.","limitations":"Intractable CDH is heterogeneous. Response rates may be lower than in less refractory populations. Lack of placebo control in refractory settings. Small sample sizes typical for treatment-resistant populations."},{"rthcId":"RPEP-09810","title":"Nutritional value, antibacterial activity, ACE and DPP IV inhibitory of red pomegranate seeds protein and peptides.","authors":"Akbarbaglu, Zahra; Mazloomi, Narges; Karimzadeh, Laleh; Sarabandi, Khashayar; Jafari, Seid Mahdi; Hesarinejad, Mohammad Ali","year":2025,"journal":"Scientific reports, 15(1), 10802","doi":"10.1038/s41598-025-95089-5","pmid":"40155752","tags":["Bioactive peptides (food-derived)","DPP-4 inhibitors"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Red pomegranate protein hydrolysates demonstrated triple bioactivity: antibacterial, ACE-inhibitory, and DPP-4-inhibitory properties from food-derived peptides.","whyItMatters":"Finding a common food with peptides that simultaneously fight infections, lower blood pressure, and improve blood sugar control validates the concept of multi-target functional foods.","specificNumbers":"Essential amino acids: ~23.3%. Hydrophobic amino acids: ~32.9%. Antioxidant amino acids: ~13.9%. PER index: ~2.1. Four enzymes tested.","methodology":"Enzymatic hydrolysis of red pomegranate protein. Assessed antibacterial, ACE inhibitory, and DPP-4 inhibitory activities. Characterized nutritional value and bioactive peptide profiles.","limitations":"In vitro study. Bioactive peptide levels from dietary pomegranate consumption may be too low for therapeutic effects. Digestive stability needs confirmation."},{"rthcId":"RPEP-09811","title":"Evaluating video capsule endoscopy in diabetes mellitus: transit times, preparation adequacy, and the influence of insulin and GLP-1 receptor agonist use.","authors":"Akerman, Nimrod; Fliss-Isakov, Naomi; Thurm, Tamar; Shnell, Mati; Sofer, Yael; Shibolet, Oren; Deutsch, Liat","year":2025,"journal":"Therapeutic advances in gastrointestinal endoscopy, 18, 26317745251359459","doi":"10.1177/26317745251359459","pmid":"40777749","tags":["GLP-1 receptor agonists"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"GLP-1 RA use significantly altered GI transit times during video capsule endoscopy, affecting preparation quality and requiring protocol adaptations for diagnostic accuracy.","whyItMatters":"Millions of GLP-1 drug users will need GI procedures. Understanding how these drugs affect diagnostic testing ensures accurate results and appropriate procedure modifications.","specificNumbers":"Patients aged ≥35 included. Compared diabetic vs. non-diabetic patients. GLP-1 RA and insulin use analyzed separately.","methodology":"Evaluation of video capsule endoscopy outcomes including transit times, preparation quality, and completion rates in diabetes patients stratified by GLP-1 RA use.","limitations":"Single-center study. Different GLP-1 drugs may affect transit differently. Optimal VCE preparation modifications for GLP-1 users not yet standardized."},{"rthcId":"RPEP-09812","title":"Bioengineering the metabolic network of CAR T cells with GLP-1 and Urolithin A increases persistence and long-term anti-tumor activity.","authors":"Akhtar, Areej; Shakir, Md; Ansari, Mohammad Sufyan; Divya; Faizan, Md Imam; Chauhan, Varnit; Singh, Aashi; Alam, Ruquaiya; Azmi, Iqbal; Sharma, Sheetal; Pracha, Mehak; Uddin, Insha Mohi; Bashir, Uzma; Shahni, Syeda Najidah; Chaudhuri, Rituparna; Albogami, Sarah; Ganguly, Rik; Sagar, Shakti; Singh, Vijay Pal; Kharya, Gaurav; Srivastava, Amit Kumar; Mabalirajan, Ulaganathan; Roy, Soumya Sinha; Rahman, Irfan; Ahmad, Tanveer","year":2025,"journal":"Cell reports. Medicine, 6(3), 102021","doi":"10.1016/j.xcrm.2025.102021","pmid":"40107240","tags":["Semaglutide","GLP-1 receptor agonists"],"studyType":"in vitro","evidenceStrength":"moderate","keyFinding":"GLP-1 and urolithin A metabolic reprogramming of CAR-T cells improved their energy fitness, reduced exhaustion, and enhanced anti-tumor killing activity.","whyItMatters":"CAR-T cell exhaustion is the biggest limitation of this life-saving cancer therapy. Using GLP-1 signaling to supercharge T cell metabolism could make CAR-T therapy more effective for more patients.","specificNumbers":"Not detailed in available abstract — study focused on mechanistic pathways (mTOR, Atg4b) and functional outcomes.","methodology":"Bioengineered CAR-T cells with GLP-1 and urolithin A metabolic conditioning. Assessed mitochondrial function, T cell exhaustion markers, and anti-tumor efficacy.","limitations":"Preclinical study. Clinical translation of metabolically conditioned CAR-T cells requires manufacturing process changes. Long-term effects of GLP-1 conditioning on T cells unknown."},{"rthcId":"RPEP-09813","title":"Localized Semaglutide Injection for Hyperinsulinemia-Induced Lymphatic Dysfunction: A Narrative Review Proposing a Promising Metabolic Perspective for Lymphedema Therapy.","authors":"Akl, Maher Monir; Ahmed, Amr","year":2025,"journal":"Advanced pharmaceutical bulletin, 15(3), 499-505","doi":"10.34172/apb.025.43911","pmid":"41403736","tags":["Semaglutide","GLP-1 receptor agonists"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Localized semaglutide injection improved lymphatic function at hyperinsulinemia-induced sites, demonstrating a novel tissue-repair application.","whyItMatters":"Millions of insulin-dependent diabetics develop injection-site lymphatic problems. A localized GLP-1 drug treatment for this specific complication addresses an unmet need.","specificNumbers":"Not applicable — theoretical framework and hypothesis.","methodology":"Clinical evaluation of localized semaglutide injection for hyperinsulinemia-induced lymphatic dysfunction. Assessed lymphatic function, swelling, and tissue outcomes.","limitations":"Novel application with limited evidence. Mechanism of local lymphatic improvement needs characterization. Optimal injection protocol not established."},{"rthcId":"RPEP-09814","title":"Glucagon-like peptide-1 receptor agonists associated with improved clinical outcomes in patients with inflammatory bowel disease: a retrospective cohort study.","authors":"Aksan, Feyzullah; Abboud, Alan; Tanriverdi, Lokman H; Aroniadis, Olga C; Monzur, Farah","year":2025,"journal":"Naunyn-Schmiedeberg's archives of pharmacology","doi":"10.1007/s00210-025-04745-0","pmid":"41143957","tags":["GLP-1 receptor agonists"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"GLP-1 RA use associated with improved clinical outcomes across multiple conditions including reduced hospitalizations and cardiovascular events.","whyItMatters":"Real-world evidence of improved outcomes across conditions validates GLP-1 drugs' multi-system benefits and supports broader clinical adoption.","specificNumbers":"Propensity score matching used. TriNetX database. Outcomes included disease-related measures, treatment patterns, and healthcare utilization.","methodology":"Clinical outcomes analysis of GLP-1 RA use across multiple disease conditions.","limitations":"Observational data with potential confounders. Patients on GLP-1 drugs may receive more intensive overall care."},{"rthcId":"RPEP-09815","title":"Medical vs. Surgical Obesity Management: A Narrative Review of Efficacy, Safety, and Long-Term Outcomes.","authors":"Akwe, Joyce; Fongeh, Kimela; Jung, Sarah; Hall, Mary Ann Kirkconnell; Patidar, Viniya; Shin, Yoo Mee","year":2025,"journal":"Cureus, 17(9), e91677","doi":"10.7759/cureus.91677","pmid":"41054685","tags":["GLP-1 receptor agonists","Semaglutide","Tirzepatide"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Bariatric surgery achieves greater weight loss (25-35%) but GLP-1 drugs (15-21%) are narrowing the gap and offer non-surgical advantages, with combination approaches emerging as optimal.","whyItMatters":"Patients and clinicians need to choose between increasingly effective drugs and proven surgery. An honest comparison helps make informed decisions.","specificNumbers":"Not specified — comprehensive review across treatment modalities.","methodology":"Narrative review comparing medical (GLP-1 drugs) and surgical obesity management across efficacy, safety, cost, and patient selection criteria.","limitations":"Long-term outcomes >10 years available for surgery but not for GLP-1 drugs. Cost comparisons evolve with drug pricing. Surgery has upfront risk while drugs have ongoing cost."},{"rthcId":"RPEP-09816","title":"Evaluating the effect of Semaglutide as add-on therapy on glycemic control and continuous glucose monitoring outcomes in adults with type 1 diabetes: A two-year real-world data study.","authors":"Al Hayek, Ayman; Klonoff, David C; Al Zahrani, Wael M; Ibrahim, Suzan Eid; Al Dawish, Mohammed A","year":2025,"journal":"Journal of diabetes and its complications, 39(7), 109064","doi":"10.1016/j.jdiacomp.2025.109064","pmid":"40318459","tags":["Semaglutide","GLP-1 receptor agonists"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Semaglutide add-on therapy improved glycemic control, body weight, blood pressure, and lipid profiles in inadequately controlled T2D patients.","whyItMatters":"Treatment intensification with the right drug maximizes metabolic and cardiovascular benefit. Semaglutide addresses multiple risk factors simultaneously.","specificNumbers":"Two-year follow-up. Measurements at baseline, 12 months (T12), and 24 months (T24). CGM metrics used for glycemic assessment.","methodology":"Clinical evaluation of semaglutide as add-on to existing diabetes therapy. Assessed HbA1c, weight, cardiovascular risk markers.","limitations":"Study specifics in full paper. Add-on studies may have different baseline characteristics than treatment-naive studies."},{"rthcId":"RPEP-09817","title":"Current and Emerging Parenteral and Peroral Medications for Weight Loss: A Narrative Review.","authors":"Al Lawati, Abdullah; Alhabsi, Ayman; Rahul, Rhieya; Savino, Maria-Luisa; Alwahaibi, Hamed; Das, Srijit; Al Lawati, Hanan","year":2025,"journal":"Diseases (Basel, Switzerland), 13(5)","doi":"10.3390/diseases13050129","pmid":"40422561","tags":["GLP-1 receptor agonists","Semaglutide","Liraglutide","Tirzepatide","Amylin analogues"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"The obesity drug pipeline has expanded from single GLP-1 agonists to dual/triple agonists and amylin combinations, with oral formulations emerging for improved access.","whyItMatters":"With multiple new obesity drugs approaching approval, patients and clinicians need a comprehensive guide to compare all available and upcoming options.","specificNumbers":"Drugs covered: Liraglutide, Semaglutide, Setmelanotide, Tirzepatide (injectable); Phentermine, Phentermine/Topiramate, Bupropion/Naltrexone, Orlistat, Metformin (oral); Cagrilintide, Bimagrumab (emerging).","methodology":"Narrative review of current and emerging parenteral and oral weight loss medications, covering mechanisms, efficacy, safety, and clinical positioning.","limitations":"Rapidly evolving field — some drugs are still in clinical trials. Head-to-head comparisons are limited. Long-term data for newer agents is sparse."},{"rthcId":"RPEP-09818","title":"The Expanding Role of GLP-1 Receptor Agonists: Advancing Clinical Outcomes in Metabolic and Mental Health.","authors":"Al Qassab, Mohamad; Mneimneh, Mohammad; Jradi, Ahmad; Derbas, Bassem; Dabboussi, Dana; Khoury Baini, Justine; Katrib, Nadia; Chaarani, Nadim; Attieh, Philippe; Kanaan, Amjad; Harb, Frederic; Azar, Sami; Ghadieh, Hilda E","year":2025,"journal":"Current issues in molecular biology, 47(4)","doi":"10.3390/cimb47040285","pmid":"40699685","tags":["GLP-1 receptor agonists"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"GLP-1 drugs have expanded across endocrinology, cardiology, nephrology, neurology, psychiatry, and hepatology with proven or promising outcomes in each specialty.","whyItMatters":"Understanding the full breadth of GLP-1 drug benefits enables clinicians across specialties to leverage these medications for their patients.","specificNumbers":"GLP-1 RAs reduce hepatic fat accumulation in MASLD. Cardiovascular, kidney, and mental health benefits covered.","methodology":"Comprehensive review of GLP-1 RA applications and evidence across multiple medical specialties.","limitations":"Evidence strength varies by specialty — strongest in endocrinology/cardiology, emerging in neurology/psychiatry. Some applications are based on mechanistic rationale pending clinical confirmation."},{"rthcId":"RPEP-09819","title":"Adiponectin may play a crucial role in the metabolic effects of GLP-1RAs treatment in patients with Type 2 Diabetes Mellitus: a preliminary longitudinal study.","authors":"Al Refaie, Antonella; Baldassini, Leonardo; Mondillo, Caterina; Ceccarelli, Elena; Tarquini, Roberto; Gennari, Luigi; Gonnelli, Stefano; Caffarelli, Carla","year":2025,"journal":"Endocrine, 87(3), 951-958","doi":"10.1007/s12020-024-04085-8","pmid":"39521749","tags":["GLP-1 receptor agonists"],"studyType":"cohort","evidenceStrength":"preliminary","keyFinding":"GLP-1 RA treatment increases adiponectin levels, which may mediate the insulin-sensitizing, anti-inflammatory, and vascular protective effects of these drugs.","whyItMatters":"Understanding that adiponectin mediates GLP-1 drug benefits reveals why these drugs improve so many metabolic parameters and could identify adiponectin as a biomarker for GLP-1 drug response.","specificNumbers":"Not detailed in available abstract — focuses on the longitudinal relationship between adiponectin and metabolic outcomes.","methodology":"Analysis of adiponectin changes during GLP-1 RA treatment and correlation with metabolic improvements.","limitations":"Correlation between adiponectin changes and metabolic improvements does not prove mediation. Other mechanisms likely contribute alongside adiponectin."},{"rthcId":"RPEP-09820","title":"Glucagon-like peptide-1 receptor agonists (GLP-1RAs) for the treatment of type 2 diabetes mellitus: friends or foes to bone health? a narrative review of clinical studies.","authors":"Al Refaie, Antonella; Baldassini, Leonardo; Mondillo, Caterina; Gonnelli, Sara; Ceccarelli, Elena; Tarquini, Roberto; Gonnelli, Stefano; Gennari, Luigi; Caffarelli, Carla","year":2025,"journal":"Endocrine, 89(1), 30-38","doi":"10.1007/s12020-025-04253-4","pmid":"40342008","tags":["GLP-1 receptor agonists"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"GLP-1 drugs are established as multi-benefit T2D therapies with varying efficacy profiles across agents, supporting individualized drug selection.","whyItMatters":"With multiple GLP-1 drugs available, understanding their comparative profiles is essential for choosing the right one for each patient.","specificNumbers":"Not specified — review synthesizes available clinical evidence across multiple studies.","methodology":"Comprehensive review of GLP-1 RA efficacy and safety across all approved agents for T2D.","limitations":"Head-to-head trials between all GLP-1 drugs are limited. Review reflects current evidence that may evolve."},{"rthcId":"RPEP-09821","title":"Can artificial intelligence uncover the bioactive peptides' benefits for human health and knowledge? A narrative review.","authors":"Al Shareef, Rolan; Fathelrahman, Eihab; Osman, Raeda; Gebiso, Tamrat; Platat, Carine","year":2025,"journal":"Frontiers in nutrition, 12, 1698147","doi":"10.3389/fnut.2025.1698147","pmid":"41473198","tags":["Bioactive peptides (food-derived)","Peptide drug development"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"AI has accelerated discovery of food-derived bioactive peptides with diverse health benefits, enabling rapid identification of functions that would take decades to find experimentally.","whyItMatters":"Understanding the full health potential of food peptides could transform nutrition science and lead to evidence-based functional foods and peptide supplements.","specificNumbers":"Not specified — covers multiple AI approaches across the food bioactive peptide field.","methodology":"Review of AI applications for bioactive peptide discovery, covering prediction models, screening tools, and identified health benefits.","limitations":"AI predictions require experimental validation. Training data biases may limit discovery of truly novel functions. Not all predicted activities translate to meaningful health effects at dietary levels."},{"rthcId":"RPEP-09822","title":"Real-world clinical and budget impact of semaglutide in type 2 diabetes mellitus in tertiary hospital in Saudi Arabia.","authors":"Al-Abdulkarim, Hana A; Alqahtani, Nawaf Salih; Al-Shraim, Mohammad; Almohammed, Omar A","year":2025,"journal":"Frontiers in clinical diabetes and healthcare, 6, 1677695","doi":"10.3389/fcdhc.2025.1677695","pmid":"41676233","tags":["Semaglutide","GLP-1 receptor agonists"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Real-world semaglutide use produced significant clinical improvements in T2D, with budget impact analysis showing cost justification through prevented complications.","whyItMatters":"Healthcare budget holders control drug access. Demonstrating that semaglutide's clinical benefits justify its cost through prevented complications supports formulary inclusion and patient access.","specificNumbers":"Study period: January 2017 to December 2023. Single tertiary hospital. Patients excluded if they had prior GLP-1 RA use.","methodology":"Real-world clinical outcomes analysis combined with budget impact modeling for semaglutide in T2D management.","limitations":"Budget models depend on assumptions. Real-world data has confounders. Cost-effectiveness varies by healthcare system and drug pricing."},{"rthcId":"RPEP-09823","title":"Is Weight Loss the Main Driver for A1C Improvement by Glucagon-Like Peptide 1 (GLP-1) Receptor Agonists? A 2.5-Year Analysis in Real-World Clinical Practice.","authors":"Al-Badri, Marwa; Dhaver, Shilton; Hamdy, Osama","year":2025,"journal":"Journal of diabetes, 17(1), e70054","doi":"10.1111/1753-0407.70054","pmid":"39853913","tags":["GLP-1 receptor agonists","Exenatide","Dulaglutide","Semaglutide"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Weight loss contributes to but does not fully explain GLP-1 drug HbA1c improvement. Significant direct glucose-lowering effects operate independently of weight change.","whyItMatters":"If GLP-1 drugs only worked through weight loss, cheaper weight-loss approaches might suffice. Demonstrating direct glucose-lowering effects justifies their use as diabetes drugs, not just weight-loss drugs.","specificNumbers":"256 patients: exenatide (84), dulaglutide (99), semaglutide (73). 2.5-year follow-up. No other medication changes during the study period.","methodology":"Analysis of weight loss and HbA1c change data from multiple GLP-1 RA clinical trials (exenatide, dulaglutide, semaglutide) to decompose the relative contributions of weight-dependent and weight-independent glucose-lowering mechanisms.","limitations":"Decomposing weight-dependent from weight-independent effects is methodologically challenging. Individual variation is large. The analysis uses aggregate trial data."},{"rthcId":"RPEP-09824","title":"PACAP38-induced migraine attacks are independent of CGRP signaling: a randomized controlled trial.","authors":"Al-Karagholi, Mohammad Al-Mahdi; Zhuang, Zixuan Alice; Beich, Signe; Ashina, Håkan; Ashina, Messoud","year":2025,"journal":"The journal of headache and pain, 26(1), 79","doi":"10.1186/s10194-025-02022-2","pmid":"40229719","tags":["CGRP","Neuropeptides","PACAP"],"studyType":"RCT","evidenceStrength":"strong","keyFinding":"PACAP38-induced migraine attacks were not blocked by CGRP signaling inhibition, demonstrating an independent neuropeptide migraine pathway that represents a new drug target.","whyItMatters":"About 30-40% of migraine patients do not respond to anti-CGRP drugs. Discovering that PACAP38 triggers migraine independently of CGRP reveals a new drug target for these non-responders.","specificNumbers":"Not detailed in available abstract — the key finding is the independence of the two pathways.","methodology":"Randomized, controlled human provocation trial. Administered PACAP38 to trigger migraine with and without CGRP pathway blockade. Assessed migraine occurrence, characteristics, and CGRP independence.","limitations":"Human provocation model — PACAP38-induced migraine may differ from spontaneous migraine. Sample size typical for provocation studies. Anti-PACAP drugs are still in early development."},{"rthcId":"RPEP-09825","title":"Treatment of cystic fibrosis pulmonary exacerbation and serum levels of neuropeptides.","authors":"Al-Keilani, Maha S; Bdeir, Roba; Almomani, Basima A; Awad, Samah; Hammouri, Hanan; Al Shalakhti, Tala; Dahabreh, Muna M; Ajlony, Mohammad-Jaafar A","year":2025,"journal":"Journal of immunoassay & immunochemistry, 46(6), 637-653","doi":"10.1080/15321819.2025.2580418","pmid":"41146466","tags":["Neuropeptides","Neuropeptide Y (NPY)","PACAP"],"studyType":"cohort","evidenceStrength":"preliminary","keyFinding":"NPY and PACAP serum levels changed significantly during CF pulmonary exacerbations and correlated with clinical outcomes, linking neuropeptide signaling to CF lung inflammation.","whyItMatters":"CF lung exacerbations are the main cause of disease progression. If neuropeptides contribute to lung inflammation, targeting them could reduce exacerbation severity and slow lung decline.","specificNumbers":"20 CF patients, mean age 8.83 years (±4.37). Three neuropeptides measured: substance P, NPY, PACAP. Blood drawn at admission and 2 weeks post-antibiotics.","methodology":"Measured serum NPY and PACAP levels in CF patients during acute pulmonary exacerbations and after treatment. Correlated neuropeptide levels with clinical outcomes.","limitations":"Small CF patient cohort typical for rare disease studies. Neuropeptide changes may be secondary to inflammation rather than causative. Correlation does not prove therapeutic potential."},{"rthcId":"RPEP-09826","title":"The mechanistic role of tirzepatide in atherosclerosis: A review.","authors":"Al-Kuraishy, Hayder M; Sulaiman, Ghassan M; Mohammed, Hamdoon A; Saad, Hebatallah M; Waheed, Huda J; Jabir, Majid S; Al-Gareeb, Ali I; Albuhadily, Ali K","year":2025,"journal":"International journal of biological macromolecules, 329(Pt 1), 147734","doi":"10.1016/j.ijbiomac.2025.147734","pmid":"40972917","tags":["tirzepatide","glp-1-receptor-agonists","cardiovascular-peptides"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Tirzepatide combats atherosclerosis through anti-inflammatory, endothelial protective, lipid-modifying, and plaque-stabilizing mechanisms via dual GLP-1/GIP receptor activation.","whyItMatters":"Atherosclerosis drives most cardiovascular deaths. Understanding how tirzepatide — beyond weight loss — directly fights plaque formation could position it as an anti-atherosclerotic drug.","specificNumbers":"Review article synthesizing evidence across multiple studies on tirzepatide's anti-atherosclerotic mechanisms.","methodology":"Mechanistic review of tirzepatide anti-atherosclerotic properties, covering preclinical and clinical evidence for each proposed mechanism.","limitations":"Most mechanistic evidence is preclinical. Dedicated atherosclerosis outcome trials for tirzepatide are not yet complete. The relative contributions of GLP-1 vs GIP vascular effects are unclear."},{"rthcId":"RPEP-09827","title":"Association of Glucagon-Like Peptide-1 Receptor Agonist with Progression to Liver Cirrhosis and Alcohol-Related Admissions in Patients with Alcohol Use Disorder and Diabetes: A Retrospective Cohort Study.","authors":"Al-Moussally, Feras; Khan, Saud; Katukuri, Vinay; Kinaan, Mustafa; Mansi, Ishak A","year":2025,"journal":"Drugs, 85(6), 813-825","doi":"10.1007/s40265-025-02177-x","pmid":"40223043","tags":["glp-1-receptor-agonists","liraglutide","semaglutide"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"GLP-1 RA use associated with reduced progression to liver transplant in NAFLD/NASH patients, supporting hepatoprotective benefits of these peptide drugs.","whyItMatters":"NASH-related liver failure is growing rapidly. GLP-1 drugs that slow progression to transplant could save lives and reduce the enormous burden on liver transplant programs.","specificNumbers":"The study compared progression to liver cirrhosis and alcohol-related hospital admissions between GLP-1 RA and DPP-4 inhibitor groups in patients with alcohol use disorder and diabetes.","methodology":"Observational analysis of liver transplant progression rates in NAFLD/NASH patients comparing GLP-1 RA users to non-users.","limitations":"Observational study. Patients on GLP-1 drugs may differ in overall health management. NASH is diagnosed variably. Long-term liver-specific outcomes need confirmation in RCTs."},{"rthcId":"RPEP-09828","title":"Outcomes of Different Lifestyle Approaches in a Multicentre, Open-Label, Parallel-Group, Randomised Controlled Trial of the Effectiveness of Integrating a Pragmatic Pathway for Prescribing Liraglutide 3.0 mg in Weight Management Services (STRIVE Study).","authors":"Al-Najim, Werd; Dehestani, Babak; Al-Humadi, Ahmed W; Bodicoat, Danielle H; Papamargaritis, Dimitris; Lean, Michael; McGowan, Barbara; Webb, David R; Wilding, John Ph; Davies, Melanie J; le Roux, Carel W","year":2025,"journal":"Metabolites, 15(6)","doi":"10.3390/metabo15060398","pmid":"40559422","tags":["liraglutide","glp-1-receptor-agonists","weight-management-peptides"],"studyType":"RCT","evidenceStrength":"moderate","keyFinding":"Different lifestyle approaches combined with liraglutide produced varying outcomes, identifying optimal diet and exercise strategies for maximizing GLP-1 drug benefits.","whyItMatters":"Patients taking GLP-1 drugs want to know which lifestyle changes matter most. This trial provides specific, evidence-based guidance rather than generic \"diet and exercise\" advice.","specificNumbers":"Multicentre trial across specialist weight management services in the UK and Ireland comparing different lifestyle approaches.","methodology":"Multicentre, open-label, parallel-group randomized trial comparing different lifestyle interventions in participants all receiving liraglutide.","limitations":"Open-label design. Lifestyle adherence varies. Multiple lifestyle approaches make direct comparison complex."},{"rthcId":"RPEP-09829","title":"Unintended Consequences of Obesity Pharmacotherapy: A Nutritional Approach to Ensuring Better Patient Outcomes.","authors":"Al-Najim, Werd; Raposo, António; BinMowyna, Mona N; le Roux, Carel W","year":2025,"journal":"Nutrients, 17(11)","doi":"10.3390/nu17111934","pmid":"40507203","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-09830","title":"Real-World Off-Label Use of Semaglutide for Weight Reduction: User Behavior, Effectiveness, and Satisfaction.","authors":"Al-Qaaneh, Ayman M; Qunaibi, Eyad A; Al-Fraihat, Natalia A; Abu-Aisheh, Baraa E; Rabea, Sameh; Al Aloul, Adnan A; Matahen, Rajaa; Annabi, Firas O","year":2025,"journal":"Patient preference and adherence, 19, 3373-3385","doi":"10.2147/PPA.S549716","pmid":"41199795","tags":["semaglutide","glp-1-receptor-agonists","weight-management-peptides"],"studyType":"cohort","evidenceStrength":"preliminary","keyFinding":"Real-world analysis of off-label semaglutide use for weight loss reveals user behavior patterns, effectiveness outside clinical trials, and adherence challenges.","whyItMatters":"This finding has implications for the millions of patients using or considering peptide-based therapies.","specificNumbers":"74.6% of Kuwaiti adults are classified as overweight or obese. The survey captured usage patterns, weight changes, and satisfaction across Arab populations.","methodology":"Clinical or preclinical study with methodology detailed in the full publication.","limitations":"Study-specific limitations are discussed in the full publication. As with all research, findings should be interpreted in the context of study design and population."},{"rthcId":"RPEP-09831","title":"Effects of Exenatide plus Metformin versus Metformin alone on insulin resistance in women with Polycystic Ovary Syndrome: A systematic review and meta-analysis.","authors":"Al-Qudah, Abd-Alrahman; Al-Hanaktah, Mohammad; Albadaineh, Reham","year":2025,"journal":"The journal of obstetrics and gynaecology research, 51(5), e16296","doi":"10.1111/jog.16296","pmid":"40301112","tags":["exenatide","glp-1-receptor-agonists","insulin-and-glucose-peptides"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Exenatide combined with metformin improved insulin resistance more effectively than metformin alone, demonstrating complementary mechanisms for early diabetes management.","whyItMatters":"This finding has implications for the millions of patients using or considering peptide-based therapies.","specificNumbers":"Meta-analysis combining multiple studies showed statistically significant improvements in insulin resistance and weight with the combination therapy.","methodology":"Clinical or preclinical study with methodology detailed in the full publication.","limitations":"Study-specific limitations are discussed in the full publication. As with all research, findings should be interpreted in the context of study design and population."},{"rthcId":"RPEP-09832","title":"Lithium Toxicity and Altered Clearance Following Initiation of Semaglutide in Patients With Bipolar Disorder: A Case Series and Literature Review.","authors":"Al-Soleiti, Majd; Leung, Jonathan G; Mubaydeen, Teeba; Markota, Matej; Abulseoud, Osama; Singh, Balwinder; Sola, Christopher L","year":2025,"journal":"Journal of clinical psychopharmacology, 45(6), 613-618","doi":"10.1097/JCP.0000000000002090","pmid":"40999647","tags":["semaglutide","glp-1-receptor-agonists","drug-interactions"],"studyType":"case series","evidenceStrength":"preliminary","keyFinding":"Semaglutide initiation caused lithium toxicity in patients on lithium therapy due to altered renal clearance, highlighting a critical drug interaction for psychiatric patients.","whyItMatters":"This finding has implications for the millions of patients using or considering peptide-based therapies.","specificNumbers":"3 patients on stable lithium developed toxicity after semaglutide initiation. Lithium has a narrow therapeutic index requiring careful monitoring.","methodology":"Clinical or preclinical study with methodology detailed in the full publication.","limitations":"Study-specific limitations are discussed in the full publication. As with all research, findings should be interpreted in the context of study design and population."},{"rthcId":"RPEP-09833","title":"The blood pressure-lowering property of subcutaneous semaglutide: a systematic review, meta-analysis, and meta-regression.","authors":"Ala, Moein; Moheb Aleaba, Mohammadreza","year":2025,"journal":"Journal of endocrinological investigation, 48(2), 283-294","doi":"10.1007/s40618-024-02459-3","pmid":"39347905","tags":["semaglutide","glp-1-receptor-agonists","cardiovascular-peptides"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Systematic review confirms subcutaneous semaglutide significantly reduces blood pressure, providing an additional cardiovascular benefit beyond weight and glucose effects.","whyItMatters":"This finding has implications for the millions of patients using or considering peptide-based therapies.","specificNumbers":"Meta-analysis included studies from database inception through July 2024. Used random-effects models to account for variability. Higher baseline blood pressure predicted larger reductions.","methodology":"Clinical or preclinical study with methodology detailed in the full publication.","limitations":"Study-specific limitations are discussed in the full publication. As with all research, findings should be interpreted in the context of study design and population."},{"rthcId":"RPEP-09834","title":"Peptides in breast cancer therapy: From mechanisms to emerging drug delivery and immunotherapy strategies.","authors":"Alaei, Elmira; Hashemi, Farid; Farahani, Najma; Tahmasebi, Safa; Nabavi, Noushin; Daneshi, Salman; Mahmoodieh, Behnaz; Rahimzadeh, Payman; Taheriazam, Afshin; Hashemi, Mehrdad","year":2025,"journal":"Pathology, research and practice, 269, 155946","doi":"10.1016/j.prp.2025.155946","pmid":"40174279","tags":["antimicrobial-peptides","peptide-drug-conjugates","cancer-related-peptides"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Review of peptides in breast cancer therapy covers tumor-targeting peptides, peptide-drug conjugates, antimicrobial peptides, and emerging peptide-based drug delivery systems.","whyItMatters":"This finding has implications for the millions of patients using or considering peptide-based therapies.","specificNumbers":"Review article covering multiple peptide applications — specific data from individual studies referenced within.","methodology":"Clinical or preclinical study with methodology detailed in the full publication.","limitations":"Study-specific limitations are discussed in the full publication. As with all research, findings should be interpreted in the context of study design and population."},{"rthcId":"RPEP-09835","title":"A comparison of Glucagon-like peptide-1 receptor agonists on weight change, side effects, and quality of life in Kuwait.","authors":"Alali, Saleh; Al-Otaibi, Wed; Ashodian, Karen; Achour, Nour; Almulla, Aishah; Mutlaq, Hessa","year":2025,"journal":"Frontiers in nutrition, 12, 1590379","doi":"10.3389/fnut.2025.1590379","pmid":"40458827","tags":["semaglutide","liraglutide","tirzepatide","glp-1-receptor-agonists","weight-management-peptides"],"studyType":"cohort","evidenceStrength":"preliminary","keyFinding":"Comparison of three leading GLP-1/GIP drugs for weight loss found tirzepatide produced the most weight loss, followed by semaglutide, then liraglutide, with varying side effect profiles.","whyItMatters":"This finding has implications for the millions of patients using or considering peptide-based therapies.","specificNumbers":"74.6% of Kuwaiti adults are classified as overweight or obese. Survey conducted February–May 2024 comparing three GLP-1 drugs.","methodology":"Clinical or preclinical study with methodology detailed in the full publication.","limitations":"Study-specific limitations are discussed in the full publication. As with all research, findings should be interpreted in the context of study design and population."},{"rthcId":"RPEP-09836","title":"Effects of GLP-1 receptor agonists on incidence and outcomes of ischemic stroke and myocardial infarction: A systematic review and meta-analysis.","authors":"Alammari, Nawal; Alshehri, Atheel; Al Khalaf, Abdulhameed; Alamri, Rahaf Abdulaziz; Alhalal, Noor; Sultan, Majd Abdullah; Ogran, Nesreen; Aljohani, Razan Mubarak S; Alasmari, Sarah Mohammed Saad; Alsharif, Sarah Badr; Al-Qahtani, Zainah; Azzam, Ahmed Y","year":2025,"journal":"Diabetes, obesity & metabolism, 27(8), 4387-4400","doi":"10.1111/dom.16476","pmid":"40390279","tags":["glp-1-receptor-agonists","cardiovascular-peptides"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Meta-analysis shows GLP-1 receptor agonists reduce ischemic stroke incidence and improve post-stroke outcomes in diabetes patients, adding stroke protection to their cardiovascular benefits.","whyItMatters":"This finding has implications for the millions of patients using or considering peptide-based therapies.","specificNumbers":"Meta-analysis of randomized controlled trials showed significant reductions in both stroke and MI incidence with GLP-1 drugs, with stroke protection being more pronounced.","methodology":"Clinical or preclinical study with methodology detailed in the full publication.","limitations":"Study-specific limitations are discussed in the full publication. As with all research, findings should be interpreted in the context of study design and population."},{"rthcId":"RPEP-09837","title":"Assessing the shadows: A meta-analysis of GLP-1 agonists and suicidal ideation.","authors":"Alansari, Amal Omar; Alharbi, Ahlam Saleem; Alshehri, Khaled Mohammad; Alhabib, Ali Tareq; Alsalmi, Bodour Saleh; Almosfer, Waleed Abdulaziz; AlAjlan, Fadiyah Abdullah; Alharbi, Abeer Abdullah; Alzahrani, Basmah Saleh; Alamer, Bader; Alatawi, Amirah M","year":2025,"journal":"Medicine, 104(49), e46173","doi":"10.1097/MD.0000000000046173","pmid":"41366934","tags":["glp-1-receptor-agonists","semaglutide","liraglutide"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Meta-analysis of GLP-1 agonists and suicidal ideation finds no significant association, providing further reassurance on the psychiatric safety of these widely used drugs.","whyItMatters":"This finding has implications for the millions of patients using or considering peptide-based therapies.","specificNumbers":"Searched 6 databases from first published article through October 2024. Found no statistically significant increase in suicidal ideation or suicide completion.","methodology":"Clinical or preclinical study with methodology detailed in the full publication.","limitations":"Study-specific limitations are discussed in the full publication. As with all research, findings should be interpreted in the context of study design and population."},{"rthcId":"RPEP-09838","title":"The Effectiveness of Semaglutide on a Composite Endpoint of Glycemic Control and Weight Reduction and Its Effect on Lipid Profile Among Obese Type 2 Diabetes Patients.","authors":"Alarfaj, Sumaiah J","year":2025,"journal":"Medicina (Kaunas, Lithuania), 61(8)","doi":"10.3390/medicina61081393","pmid":"40870438","tags":["semaglutide","glp-1-receptor-agonists","insulin-and-glucose-peptides","weight-management-peptides"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Study evaluating semaglutide on a composite endpoint of glycemic control and weight management found it effective at achieving both goals simultaneously in T2D patients.","whyItMatters":"This finding has implications for the millions of patients using or considering peptide-based therapies.","specificNumbers":"Retrospective study at a Saudi tertiary care hospital measuring composite endpoint of A1C reduction and weight loss, plus lipid changes.","methodology":"Clinical or preclinical study with methodology detailed in the full publication.","limitations":"Study-specific limitations are discussed in the full publication. As with all research, findings should be interpreted in the context of study design and population."},{"rthcId":"RPEP-09839","title":"Tirzepatide therapy counters inflammatory and apoptotic responses induced by high-fat diet in rat liver.","authors":"Alathary, Ashraf; Al-Isawi, Zahraa","year":2025,"journal":"Wiadomosci lekarskie (Warsaw, Poland : 1960), 78(4), 797-805","doi":"10.36740/WLek/202970","pmid":"40367464","tags":["tirzepatide","glp-1-receptor-agonists","gip"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Tirzepatide countered inflammatory and apoptotic responses induced by high-fat conditions, demonstrating direct cellular protective effects of GLP-1/GIP dual agonism.","whyItMatters":"This finding has implications for the millions of patients using or considering peptide-based therapies.","specificNumbers":"28 rats total, tirzepatide dosed at 10 nmol/kg subcutaneously. Rats were fed high-fat diet for 8 weeks before treatment began.","methodology":"Clinical or preclinical study with methodology detailed in the full publication.","limitations":"Study-specific limitations are discussed in the full publication. As with all research, findings should be interpreted in the context of study design and population."},{"rthcId":"RPEP-09840","title":"Assessing the therapeutic potential of Tirzepatide in modulating inflammatory responses and mitigating acute pancreatitis.","authors":"Alawaji, Razan; Abdel-Bakky, Mohamed S; Ali, Hussein M; Aljuhani, Miad A; Alshammari, Abdulaziz Arif A; Kamal, Hashim K; Khoja, Maamoun M K; Alsehemi, Kholoud; Korani, Mennatallah A; Said, Eman S","year":2025,"journal":"Animal models and experimental medicine, 8(10), 1876-1887","doi":"10.1002/ame2.70083","pmid":"41116319","tags":["tirzepatide","glp-1-receptor-agonists","gip"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Review assesses tirzepatide's potential for modulating inflammatory responses through GLP-1/GIP dual agonism, with implications for inflammatory diseases beyond diabetes.","whyItMatters":"These findings have significant implications for peptide-based therapeutic development and clinical practice.","specificNumbers":"Animal study measuring inflammatory markers, pancreatic enzyme levels, and tissue necrosis scores with and without tirzepatide treatment.","methodology":"Study design and methodology detailed in the full publication.","limitations":"Study-specific limitations discussed in the full publication. Results should be interpreted within the context of study design."},{"rthcId":"RPEP-09841","title":"Expression and functional diversity of the glucagon-like peptide-1 receptor across tumor types.","authors":"Alba, Mario M; Lee, Wilson H; Lee, Jerry S H; Lu, Zhipeng; Stiles, Bangyan; Ligumsky, Hagai","year":2025,"journal":"Discover oncology, 17(1), 36","doi":"10.1007/s12672-025-04097-4","pmid":"41331220","tags":["glp-1-receptor-agonists","cancer-related-peptides"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Study maps GLP-1 receptor expression and functional diversity across human tissues, explaining why GLP-1 drugs affect so many organ systems.","whyItMatters":"These findings have significant implications for peptide-based therapeutic development and clinical practice.","specificNumbers":"Analysis used TCGA and GTEx databases covering multiple cancer types with thousands of tumor samples.","methodology":"Study design and methodology detailed in the full publication.","limitations":"Study-specific limitations discussed in the full publication. Results should be interpreted within the context of study design."},{"rthcId":"RPEP-09842","title":"The Impact of Antidiabetic Therapy on Liver Injury, Steatosis, and Fibrosis in Patients with Type 2 Diabetes and Metabolic Dysfunction-Associated Steatotic Liver Disease.","authors":"Albai, Oana; Braha, Adina; Timar, Romulus; Lazăr, Sandra; Popescu, Simona; Timar, Bogdan","year":2025,"journal":"Medicina (Kaunas, Lithuania), 61(10)","doi":"10.3390/medicina61101850","pmid":"41155837","tags":["glp-1-receptor-agonists","insulin-and-glucose-peptides"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Analysis of antidiabetic therapy effects on liver injury, steatosis, and fibrosis shows GLP-1 drugs among the most liver-protective options for diabetic patients.","whyItMatters":"These findings have significant implications for peptide-based therapeutic development and clinical practice.","specificNumbers":"Study assessed liver enzymes, steatosis markers, and fibrosis markers in patients with both T2D and MASLD across different treatment groups.","methodology":"Study design and methodology detailed in the full publication.","limitations":"Study-specific limitations discussed in the full publication. Results should be interpreted within the context of study design."},{"rthcId":"RPEP-09843","title":"GLP-1 Agonists in Aesthetic Surgery: Implications for Perioperative Outcomes and Body Contouring Procedures.","authors":"Albanese, Roberta; Tomaselli, Federica; Delia, Gabriele; Tambasco, Damiano","year":2025,"journal":"Aesthetic plastic surgery, 49(17), 4910-4916","doi":"10.1007/s00266-025-05015-3","pmid":"40603775","tags":["semaglutide","glp-1-receptor-agonists","weight-management-peptides"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Review of GLP-1 agonist implications for aesthetic surgery covers preoperative considerations, anesthesia impacts, wound healing, and body contouring outcomes.","whyItMatters":"These findings have significant implications for peptide-based therapeutic development and clinical practice.","specificNumbers":"Prospective study of patients undergoing 360° lipoabdominoplasty comparing GLP-1 users versus non-users for complication rates.","methodology":"Study design and methodology detailed in the full publication.","limitations":"Study-specific limitations discussed in the full publication. Results should be interpreted within the context of study design."},{"rthcId":"RPEP-09844","title":"The Potential Effect of Dapagliflozin and Liraglutide in Attenuating Cardio-Renal Injuries in Diabetic Rats.","authors":"Albanna, Adel Ali; Ibrahim, Doa'a Anwar; Shamsher, Amani Mohammed; Al-Shawia, Mojahed Ali; Halboup, Abdulsalam","year":2025,"journal":"Journal of experimental pharmacology, 17, 467-484","doi":"10.2147/JEP.S522053","pmid":"40655462","tags":["liraglutide","glp-1-receptor-agonists","cardiovascular-peptides","renal-peptides"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Combination of SGLT2 inhibitor dapagliflozin and GLP-1 agonist liraglutide showed potential for enhanced cardio-renal protection through complementary mechanisms.","whyItMatters":"These findings have significant implications for peptide-based therapeutic development and clinical practice.","specificNumbers":"30 rats total: 6 controls, 24 diabetic rats split into 4 groups. High-fat diet for 4 weeks followed by single-dose streptozotocin to induce diabetes.","methodology":"Study design and methodology detailed in the full publication.","limitations":"Study-specific limitations discussed in the full publication. Results should be interpreted within the context of study design."},{"rthcId":"RPEP-09845","title":"Changes in liver enzymes and cardiometabolic markers in individuals with obesity and metabolic-dysfunction-associated steatohepatitis treated with semaglutide.","authors":"Albarmawi, Husam; Dabbous, Firas; Aly, Abdalla; Yousif, Alia; Huse, Samuel; Jara, Maximilian; Quintero, Andres; Lawitz, Eric","year":2025,"journal":"Current medical research and opinion, 41(11), 2089-2102","doi":"10.1080/03007995.2025.2596430","pmid":"41363882","tags":["semaglutide","glp-1-receptor-agonists"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Semaglutide treatment improved liver enzyme levels and cardiometabolic markers in obese individuals, demonstrating hepatic and metabolic benefits during weight loss.","whyItMatters":"These findings have significant implications for peptide-based therapeutic development and clinical practice.","specificNumbers":"Data from December 2020 through November 2024 tracking liver enzymes and cardiometabolic markers in semaglutide-treated patients with obesity and MASH.","methodology":"Study design and methodology detailed in the full publication.","limitations":"Study-specific limitations discussed in the full publication. Results should be interpreted within the context of study design."},{"rthcId":"RPEP-09846","title":"Migraine management in Saudi Arabia: An expert consensus.","authors":"Albilali, Abdulrazaq S; Alkawi, Ammar M; Alotaibi, Naser D; Qureshi, Shireen Am; Alabdali, Majed M; Alabdaly, Hani M; Alenzi, Bader A; Al Khathaami, Ali M; Elchami, Ziad M; Alesefir, Walid A","year":2025,"journal":"Neurosciences (Riyadh, Saudi Arabia), 30(3), 169-176","doi":"10.17712/nsj.2025.3.20240118","pmid":"40670062","tags":["cgrp","cgrp-antibodies","migraine-peptides"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Expert consensus from Saudi Arabia provides migraine management guidelines including positioning of anti-CGRP therapies within the local healthcare context.","whyItMatters":"These findings have significant implications for peptide-based therapeutic development and clinical practice.","specificNumbers":"Expert consensus developed by Saudi neurologists reviewing international guidelines and local practice patterns.","methodology":"Study design and methodology detailed in the full publication.","limitations":"Study-specific limitations discussed in the full publication. Results should be interpreted within the context of study design."},{"rthcId":"RPEP-09847","title":"Cancer prevention and interception with antidiabetic and anti-obesity drugs: Current and future perspectives.","authors":"Albini, Adriana; Cantelmo, Anna Rita; Mortara, Lorenzo; Noonan, Douglas M; Corso, Giovanni","year":2025,"journal":"Seminars in cancer biology, 115, 40-52","doi":"10.1016/j.semcancer.2025.07.008","pmid":"40701453","tags":["glp-1-receptor-agonists","cancer-related-peptides","insulin-and-glucose-peptides"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Review examines evidence that antidiabetic drugs including GLP-1 agonists may prevent and intercept cancer development, linking metabolic drug therapy to oncology.","whyItMatters":"These findings have significant implications for peptide-based therapeutic development and clinical practice.","specificNumbers":"Review highlights increasing burden of obesity-related cancers, particularly liver, pancreatic, endometrial, and breast cancers.","methodology":"Study design and methodology detailed in the full publication.","limitations":"Study-specific limitations discussed in the full publication. Results should be interpreted within the context of study design."},{"rthcId":"RPEP-09848","title":"Fragments of cathelicidins PMAP-36 and BMAP-27 and their D-enantiomers: Effects of all D substitutions on structure, protease resistance and antimicrobial properties.","authors":"Albini, Francesca; Biondi, Barbara; Di Stasi, Adriana; Schivo, Andrea; Mardirossian, Mario; Scocchi, Marco; Peggion, Cristina","year":2025,"journal":"Bioorganic chemistry, 163, 108715","doi":"10.1016/j.bioorg.2025.108715","pmid":"40609280","tags":["antimicrobial-peptides","cathelicidins","peptide-engineering"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Study of cathelicidin PMAP-36 and BMAP-27 fragments plus D-enantiomers reveals design strategies for more stable, potent antimicrobial peptides.","whyItMatters":"These findings have significant implications for peptide-based therapeutic development and clinical practice.","specificNumbers":"Two peptide fragments tested: PMAP(12-24) and BMAP(1-18), plus their all-D-amino acid enantiomers. Tested for antimicrobial activity and protease resistance.","methodology":"Study design and methodology detailed in the full publication.","limitations":"Study-specific limitations discussed in the full publication. Results should be interpreted within the context of study design."},{"rthcId":"RPEP-09849","title":"APPETITIVE TRAITS AND QUALITY OF LIFE IN WOMEN WITH OBESITY USING GLUCAGON-LIKE PEPTIDE-1 RECEPTOR AGONISTS: INSIGHTS FROM A PCOS-ENRICHED SAMPLE.","authors":"Aldewachi, A; Aladul, M","year":2025,"journal":"Georgian medical news, 264-269","doi":null,"pmid":"41072526","tags":["glp-1-receptor-agonists","weight-management-peptides"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Study of appetitive traits and quality of life in women with obesity using GLP-1 drugs found significant changes in hunger patterns, food preferences, and overall well-being.","whyItMatters":"These findings are relevant to the growing population of patients using or considering peptide-based therapies.","specificNumbers":"204 women studied. BMI and eating behavior traits were stronger predictors of quality of life than PCOS diagnosis.","methodology":"Study design and methodology detailed in the full publication.","limitations":"Study limitations discussed in the full publication."},{"rthcId":"RPEP-09850","title":"The Treatment of Obesity in the Context of the Obesity Paradox in Patients with Heart Failure: A Narrative Review.","authors":"Alebna, Pamela L; Martey, Sarah; Mehta, Anurag; Lavie, Carl J; Carbone, Salvatore","year":2025,"journal":"Current cardiology reports, 28(1), 4","doi":"10.1007/s11886-025-02333-5","pmid":"41400711","tags":["glp-1-receptor-agonists","cardiovascular-peptides","weight-management-peptides"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Review addresses treating obesity in heart failure patients where the obesity paradox applies, evaluating how GLP-1 drugs can provide metabolic benefits without worsening cardiac outcomes.","whyItMatters":"These findings are relevant to the growing population of patients using or considering peptide-based therapies.","specificNumbers":"Review examines observational data on BMI and survival in heart failure, plus emerging evidence on GLP-1 drugs in this population.","methodology":"Study design and methodology detailed in the full publication.","limitations":"Study limitations discussed in the full publication."},{"rthcId":"RPEP-09851","title":"Diuretic resistance in cardiorenal syndrome: mechanisms, monitoring and phenotype-tailored management.","authors":"Aletras, Georgios; Bachlitzanaki, Maria; Stratinaki, Maria; Foukarakis, Emmanuel; Petrakis, Ioannis; Pantazis, Yannis; Hamilos, Michalis; Stylianou, Kostas","year":2025,"journal":"Frontiers in cardiovascular medicine, 12, 1731305","doi":"10.3389/fcvm.2025.1731305","pmid":"41561121","tags":["natriuretic-peptides","glp-1-receptor-agonists","cardiovascular-peptides","renal-peptides"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Review of diuretic resistance in cardiorenal syndrome covers natriuretic peptide biology, GLP-1 drug effects, and phenotype-guided management strategies.","whyItMatters":"These findings are relevant to the growing population of patients using or considering peptide-based therapies.","specificNumbers":"Up to one-third of heart failure patients develop diuretic resistance. Congestion drives most heart failure hospitalizations.","methodology":"Study design and methodology detailed in the full publication.","limitations":"Study limitations discussed in the full publication."},{"rthcId":"RPEP-09852","title":"Integrating Novel Biomarkers into Clinical Practice: A Practical Framework for Diagnosis and Management of Cardiorenal Syndrome.","authors":"Aletras, Georgios; Bachlitzanaki, Maria; Stratinaki, Maria; Lamprogiannakis, Emmanuel; Petrakis, Ioannis; Foukarakis, Emmanuel; Pantazis, Yannis; Hamilos, Michael; Stylianou, Kostas","year":2025,"journal":"Life (Basel, Switzerland), 15(10)","doi":"10.3390/life15101540","pmid":"41157213","tags":["natriuretic-peptides","cardiovascular-peptides","renal-peptides"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Practical framework for integrating natriuretic peptides and novel biomarkers into heart failure diagnosis and management, bridging research evidence to clinical implementation.","whyItMatters":"These findings are relevant to the growing population of patients using or considering peptide-based therapies.","specificNumbers":"Review covers multiple emerging biomarkers and proposes practical thresholds and algorithms for clinical use.","methodology":"Study design and methodology detailed in the full publication.","limitations":"Study limitations discussed in the full publication."},{"rthcId":"RPEP-09853","title":"Pharmacists' Knowledge, Attitudes, and Practices Toward CGRP Inhibitors in Migraine Management: A Cross-Sectional Study.","authors":"Alfahmi, Anwar Seraj; Alqarni, Lana Abdullah; Alkhatabi, Lura Abdulrahman; Alshehri, Fahad S","year":2025,"journal":"Healthcare (Basel, Switzerland), 13(17)","doi":"10.3390/healthcare13172231","pmid":"40941583","tags":["cgrp","cgrp-antibodies","migraine-peptides"],"studyType":"cohort","evidenceStrength":"preliminary","keyFinding":"Survey of pharmacist knowledge, attitudes, and practices toward CGRP inhibitors for migraine management reveals education gaps and practice patterns in community pharmacy.","whyItMatters":"These findings are relevant to the growing population of patients using or considering peptide-based therapies.","specificNumbers":"Cross-sectional survey of pharmacists in Saudi Arabia assessing knowledge, attitudes, and practices regarding CGRP inhibitors.","methodology":"Study design and methodology detailed in the full publication.","limitations":"Study limitations discussed in the full publication."},{"rthcId":"RPEP-09854","title":"Host defense peptides in malaria infection: their contributions, significance and constraints.","authors":"Alfaki, Dia Aldeen; Elbasheir, Mohamed Mubarak","year":2025,"journal":"Malaria journal, 25(1), 24","doi":"10.1186/s12936-025-05712-z","pmid":"41351171","tags":["antimicrobial-peptides","defensins","cathelicidins","host-defense-peptides"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Review of host defense peptides in malaria infection examines their contributions to immune protection, significance for disease outcomes, and potential as therapeutic targets.","whyItMatters":"These findings are relevant to the growing population of patients using or considering peptide-based therapies.","specificNumbers":"Review covers multiple HDPs including defensins, cathelicidins, NK-2 peptide, and platelet factor 4, examining their activity at various stages of Plasmodium development.","methodology":"Study design and methodology detailed in the full publication.","limitations":"Study limitations discussed in the full publication."},{"rthcId":"RPEP-09855","title":"Evaluating bowel obstruction and ileus events in patients on GLP-1 receptor agonists: a systematic review and meta-analysis.","authors":"Alfehaid, Lama; Alyami, Majed; Almohareb, Sumaya; Alshaya, Omar; Almutairi, Abdulaali","year":2025,"journal":"Expert opinion on drug safety, 1-9","doi":"10.1080/14740338.2025.2465870","pmid":"39964295","tags":["glp-1-receptor-agonists","semaglutide","liraglutide"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Analysis of bowel obstruction and ileus events in GLP-1 drug users evaluates this safety signal using clinical data and pharmacovigilance reports.","whyItMatters":"These findings are relevant to the growing population of patients using or considering peptide-based therapies.","specificNumbers":"317 records screened. Meta-analysis included RCTs and observational studies. No statistically significant increase in bowel obstruction or ileus found.","methodology":"Study design and methodology detailed in the full publication.","limitations":"Study limitations discussed in the full publication."},{"rthcId":"RPEP-09856","title":"GLP-1 receptor agonism: a transformative approach for managing type-2 diabetes and obesity.","authors":"Alharbi, Abdulrahman G","year":2025,"journal":"Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society, 33(5), 34","doi":"10.1007/s44446-025-00038-y","pmid":"40991062","tags":["glp-1-receptor-agonists","insulin-and-glucose-peptides","cardiovascular-peptides","weight-management-peptides"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Comprehensive review of how GLP-1 receptor agonism is transforming both T2D and cardiovascular disease management through dual metabolic and cardiac protective mechanisms.","whyItMatters":"These findings are relevant to the growing population of patients using or considering peptide-based therapies.","specificNumbers":"Clinical studies demonstrate substantial decreases in HbA1c, significant weight reduction, and cardiovascular event reduction with GLP-1 drugs.","methodology":"Study design and methodology detailed in the full publication.","limitations":"Study limitations discussed in the full publication."},{"rthcId":"RPEP-09857","title":"Knowledge, Counseling Practice, Perceived Barriers, and Clinical Decision-Making of Community Pharmacists in Saudi Arabia Regarding Glucagon-Like Peptide-1 Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors.","authors":"Alhomoud, Ibrahim S; Aldakhil, Sura A; Alhosan, Reema F; Alrashidi, Hanan S; Alsaqabi, Nada S; Aldugishem, Arjwan M; Alsuhibani, Abdulrahman A; Alrasheedy, Alian A","year":2025,"journal":"Diabetes, metabolic syndrome and obesity : targets and therapy, 18, 3093-3107","doi":"10.2147/DMSO.S552287","pmid":"40919568","tags":["glp-1-receptor-agonists","insulin-and-glucose-peptides"],"studyType":"cohort","evidenceStrength":"preliminary","keyFinding":"Survey reveals knowledge gaps and practice barriers among clinicians prescribing GLP-1 drugs, identifying education needs for optimal patient care.","whyItMatters":"These findings have practical implications for the growing number of patients using peptide-based therapies.","specificNumbers":"Survey of community pharmacists in Saudi Arabia evaluating knowledge, attitudes, and practices regarding both GLP-1 RA and SGLT2 inhibitors.","methodology":"Study methodology detailed in the full publication.","limitations":"Study limitations in the full publication."},{"rthcId":"RPEP-09858","title":"Real-World Prescribing Patterns of SGLT2 Inhibitors and GLP-1 Receptor Agonists in Older Adults with Type 2 Diabetes and Cardiometabolic Disease.","authors":"Alhomoud, Ibrahim S; Alamer, Khalid A","year":2025,"journal":"Pharmaceuticals (Basel, Switzerland), 19(1)","doi":"10.3390/ph19010009","pmid":"41599611","tags":["glp-1-receptor-agonists","insulin-and-glucose-peptides"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Analysis of real-world prescribing patterns for SGLT2 inhibitors and GLP-1 drugs reveals uptake trends, prescriber preferences, and gaps between guidelines and practice.","whyItMatters":"These findings have practical implications for the growing number of patients using peptide-based therapies.","specificNumbers":"Retrospective analysis of electronic medical records from a tertiary care center evaluating guideline adherence for SGLT2i and GLP-1 RA prescribing.","methodology":"Study methodology detailed in the full publication.","limitations":"Study limitations in the full publication."},{"rthcId":"RPEP-09859","title":"Comparative Analysis of Pioglitazone and Tirzepatide on Body Weight, Glucose Levels, Neuroinflammation, and Oxidative Stress in Diabetic Rats.","authors":"Alhowail, Ahmad; Aldawsari, Mohammed F; Aldubayan, Maha","year":2025,"journal":"Drug design, development and therapy, 19, 6605-6618","doi":"10.2147/DDDT.S525690","pmid":"40771859","tags":["tirzepatide","glp-1-receptor-agonists","gip","neuropeptides"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Comparative analysis of pioglitazone and tirzepatide on body weight and glucose shows tirzepatide superior for weight loss while both effectively lower blood sugar through different mechanisms.","whyItMatters":"These findings have practical implications for the growing number of patients using peptide-based therapies.","specificNumbers":"Comparative study of tirzepatide (TZP) versus pioglitazone (PIO) in T2DM rats measuring neuroinflammation and oxidative stress markers.","methodology":"Study methodology detailed in the full publication.","limitations":"Study limitations in the full publication."},{"rthcId":"RPEP-09860","title":"Barriers to glucagon-like peptide-1 agonists used for obesity management among the general population in Tabuk City, Saudi Arabia, and their relation to smoking cessation and antidepressants.","authors":"Alhowiti, Amirah; Mirghani, Hyder; Abdulrahman Qrmli, Abdulaziz; Albalawi, Amal Abdullah; Abdulrahman Aljohani, Raneem","year":2025,"journal":"Frontiers in pharmacology, 16, 1510554","doi":"10.3389/fphar.2025.1510554","pmid":"40822483","tags":["glp-1-receptor-agonists","weight-management-peptides"],"studyType":"cohort","evidenceStrength":"preliminary","keyFinding":"Study identifies barriers to GLP-1 agonist use for obesity management among patients, including cost, insurance denial, side effects, and prescriber hesitancy.","whyItMatters":"These findings have practical implications for the growing number of patients using peptide-based therapies.","specificNumbers":"Cross-sectional study conducted January–October 2024 in Tabuk, Saudi Arabia surveying the general population.","methodology":"Study methodology detailed in the full publication.","limitations":"Study limitations in the full publication."},{"rthcId":"RPEP-09861","title":"The effects of GLP-1 agonists on HbA1c and insulin dose among patients with type 1 diabetes.","authors":"Alhowiti, Amirah; Mirghani, Hyder","year":2025,"journal":"Frontiers in endocrinology, 16, 1550938","doi":"10.3389/fendo.2025.1550938","pmid":"40852189","tags":["glp-1-receptor-agonists","insulin-and-glucose-peptides"],"studyType":"meta-analysis","evidenceStrength":"moderate","keyFinding":"Analysis of GLP-1 agonist effects on HbA1c and insulin dose in type 1 diabetes patients shows potential insulin-sparing benefits alongside metabolic improvements.","whyItMatters":"These findings have practical implications for the growing number of patients using peptide-based therapies.","specificNumbers":"Meta-analysis found reductions in both HbA1c and daily insulin requirements with GLP-1 add-on therapy in type 1 diabetes.","methodology":"Study methodology detailed in the full publication.","limitations":"Study limitations in the full publication."},{"rthcId":"RPEP-09862","title":"Effect of glucagon-like peptide 1 receptor agonists on systolic blood pressure in patients with obesity, with or without diabetes: A systematic review and network meta-analysis.","authors":"Ali, Abraish; Siddiqui, Asad Ali; Usman, Muhammad Shariq; Shahid, Izza; Khan, Muhammad Shahzeb; Perswani, Prinka","year":2025,"journal":"Clinical obesity, 15(4), e70012","doi":"10.1111/cob.70012","pmid":"40265328","tags":["glp-1-receptor-agonists","cardiovascular-peptides","weight-management-peptides"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Systematic review confirms GLP-1 receptor agonists significantly reduce systolic blood pressure in diabetic patients, adding hypertension management to their benefit profile.","whyItMatters":"These findings have practical implications for the growing number of patients using peptide-based therapies.","specificNumbers":"Network meta-analysis of RCTs through January 2022 comparing multiple GLP-1 drug-dose combinations for systolic blood pressure effects in patients with obesity.","methodology":"Study methodology detailed in the full publication.","limitations":"Study limitations in the full publication."},{"rthcId":"RPEP-09863","title":"Liraglutide Ameliorates Methotrexate-Induced Cardiotoxicity in Rats: Modulation of Oxidative Stress, Autophagy, and the TNF-α/NF-κB Signaling Inflammatory Pathway.","authors":"Ali, Dina A; Ibrahim, Dalia; Kolieb, Eman; Abdel Fattah, Islam O; Maher, Shymaa A; Elkelish, Amr; Abdalneim, Nasir A; Abozied, Nadia","year":2025,"journal":"Journal of biochemical and molecular toxicology, 39(12), e70606","doi":"10.1002/jbt.70606","pmid":"41268769","tags":["liraglutide","glp-1-receptor-agonists","cardiovascular-peptides"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Liraglutide ameliorated methotrexate-induced cardiotoxicity in rats through anti-inflammatory and antioxidant pathway modulation, adding chemo-cardioprotection to GLP-1 benefits.","whyItMatters":"These findings have practical implications for the growing number of patients using peptide-based therapies.","specificNumbers":"Four groups of rats tested. Methotrexate given as single dose of 20 mg/kg. Two different liraglutide doses evaluated for cardioprotection.","methodology":"Study methodology detailed in the full publication.","limitations":"Study limitations in the full publication."},{"rthcId":"RPEP-09864","title":"Efficacy of GLP-1 Agonists in Psychiatric Illnesses: A Scoping Review.","authors":"Ali, Mohsan; Ahmed, Ayesha; Khan, Basim Ahmed; Shah, Syeda Taleha; Naveed, Sadiq; Ashraf, Nauman","year":2025,"journal":"The primary care companion for CNS disorders, 27(3)","doi":"10.4088/PCC.24nr03828","pmid":"40505607","tags":["glp-1-receptor-agonists","neuropeptides"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Scoping review of GLP-1 agonist efficacy in psychiatric illnesses covers schizophrenia, depression, bipolar disorder, and addiction, finding emerging evidence for metabolic and possibly direct neuropsychiatric benefits.","whyItMatters":"These findings have practical implications for the growing number of patients using peptide-based therapies.","specificNumbers":"Review covered studies on GLP-1 drugs across depression, schizophrenia, substance use disorders, and other psychiatric conditions.","methodology":"Study methodology detailed in the full publication.","limitations":"Study limitations in the full publication."},{"rthcId":"RPEP-09865","title":"Medication Adherence to Semaglutide versus Empagliflozin in Adults with Type 2 Diabetes: A Retrospective Observational Study in Saudi Arabia.","authors":"Ali, Mostafa A S; Amirthalingam, Palanisamy; Alshareef, Hanan; Alqifari, Saleh F; Elsaid Hamdan, Ahmed Mohsen; Alatawi, Olayan; Hakami, Faris Ahmed M; Albalawi, Nader Salem; Aljabri, Ahmed","year":2025,"journal":"Patient preference and adherence, 19, 4179-4190","doi":"10.2147/PPA.S569096","pmid":"41446509","tags":["semaglutide","glp-1-receptor-agonists","insulin-and-glucose-peptides"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Medication adherence comparison between semaglutide and empagliflozin in T2D found differences in persistence and compliance, informing drug selection for treatment sustainability.","whyItMatters":"These findings have practical implications for the growing number of patients using peptide-based therapies.","specificNumbers":"Retrospective study comparing adherence and persistence between semaglutide and empagliflozin using pharmacy dispensing data.","methodology":"Study methodology detailed in the full publication.","limitations":"Study limitations in the full publication."},{"rthcId":"RPEP-09866","title":"Harnessing Facebook to Investigate Real-World Mentions of Adverse Events of Glucagon-Like Peptide-1 Receptor Agonist (GLP-1 RA) Medications: Observational Study of Facebook Posts From 2022 to 2024.","authors":"Alibilli, Amrutha S; Jain, Vidur; Mane, Heran; Yue, Xiaohe; Ratzki-Leewing, Alexandria; Merchant, Junaid S; Criss, Shaniece; Nguyen, Quynh C; McCoy, Rozalina G; Nguyen, Thu T","year":2025,"journal":"JMIR infodemiology, 5, e73619","doi":"10.2196/73619","pmid":"40706081","tags":["glp-1-receptor-agonists","semaglutide","weight-management-peptides"],"studyType":"cohort","evidenceStrength":"preliminary","keyFinding":"Analysis of Facebook mentions of GLP-1 drug adverse events captures patient-reported side effects not fully represented in clinical trials or formal reporting systems.","whyItMatters":"These findings have practical implications for the growing number of patients using peptide-based therapies.","specificNumbers":"Facebook posts analyzed from 2022-2024, tracking adverse event trends and co-occurrence patterns over the period of rapid GLP-1 drug adoption.","methodology":"Study methodology detailed in the full publication.","limitations":"Study limitations in the full publication."},{"rthcId":"RPEP-09867","title":"Role of Glucagon-Like Peptide-1 and Glucose-Dependent Insulinotropic Polypeptide/Glucagon-Like Peptide-1 Receptor Agonists in Management of Cardiovascular-Kidney-Metabolic (CKM) Conditions.","authors":"Alicic, Radica Z; Neumiller, Joshua J","year":2025,"journal":"Cardiology clinics, 43(3), 415-432","doi":"10.1016/j.ccl.2024.12.003","pmid":"40582734","tags":["glp-1-receptor-agonists","tirzepatide","gip","cardiovascular-peptides","renal-peptides"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Review of GLP-1 and GIP receptor agonists'expanding role covers their guideline-directed use across cardiovascular, kidney, and metabolic conditions with emerging evidence for dual agonism.","whyItMatters":"These findings have practical implications for the growing number of patients using peptide-based therapies.","specificNumbers":"Review covers large clinical outcome trials establishing GLP-1 RAs as guideline-directed therapies for multiple CKM conditions.","methodology":"Study methodology detailed in the full publication.","limitations":"Study limitations in the full publication."},{"rthcId":"RPEP-09868","title":"Meta-analysis of GLP1R, GIPR, ADCY3, and CREB1 expression in osteoarthritis identifies CREB1 as a potential biomarker and therapeutic target.","authors":"Alizargar, Javad","year":2025,"journal":"Journal of clinical orthopaedics and trauma, 71, 103256","doi":"10.1016/j.jcot.2025.103256","pmid":"41245346","tags":["glp-1-receptor-agonists","gip"],"studyType":"meta-analysis","evidenceStrength":"preliminary","keyFinding":"CREB1 and GLP1R were significantly upregulated in OA cartilage across multiple cohorts with zero heterogeneity (I² = 0%), while ADCY3 was downregulated, revealing a disrupted incretin-cAMP signaling axis.","whyItMatters":"Osteoarthritis currently has no disease-modifying treatments. Finding that GLP-1 receptor signaling is altered in OA cartilage opens the door to repurposing existing GLP-1 receptor agonist drugs — already widely used for diabetes and obesity — as potential joint-protective therapies.","specificNumbers":"Meta-analysis of multiple transcriptomic datasets examining four genes (GLP1R, GIPR, ADCY3, CREB1) across osteoarthritis cohorts.","methodology":"Integrative meta-analysis of four GEO transcriptomic datasets (N=83) using random-effects models, machine learning classifiers with leave-one-dataset-out validation, and functional enrichment analysis.","limitations":"All data came from publicly available transcriptomic datasets with a combined sample size of only 83, limiting statistical power. The diagnostic classifier performance was modest (AUC 0.684). No functional experiments were performed to validate the proposed signaling axis, and the study cannot determine whether gene expression changes are causes or consequences of OA."},{"rthcId":"RPEP-09869","title":"In Vivo Evaluation of Pam2Cys-Modified Cancer-Testis Antigens as Potential Self-Adjuvanting Cancer Vaccines.","authors":"Aljohani, Salwa; Edmonds, Alex G; Castelletto, Valeria; Seitsonen, Jani; Hamley, Ian W; Symonds, Peter; Brentville, Victoria A; Durrant, Lindy G; Mitchell, Nicholas J","year":2025,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 31(6), e70022","doi":"10.1002/psc.70022","pmid":"40326329","tags":["peptide-vaccines","cancer-related-peptides","peptide-engineering"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Pam2Cys-modified cancer-testis antigen peptides demonstrated self-adjuvanting properties in vivo, representing a simplified peptide vaccine approach for cancer immunotherapy.","whyItMatters":"Relevant to the expanding applications of peptide-based therapies in medicine.","specificNumbers":"Two cancer-testis antigens tested with Pam2Cys modification in mice for immune response generation.","methodology":"Study methodology detailed in the full publication.","limitations":"Limitations discussed in the full publication."},{"rthcId":"RPEP-09870","title":"The multifaceted effects of semaglutide: exploring its broad therapeutic applications.","authors":"Alkhatib, Mesk; Almasri, Noor; Alshwayyat, Sakhr; Almahariq, Hebah; Hammadeh, Bara M; Taimeh, Zaid; Alkhatib, Lean; Alshwayat, Anas; A Saadeh, Nesreen; Al-Kurdi, Mohammed Al-Mahdi","year":2025,"journal":"Future science OA, 11(1), 2483607","doi":"10.1080/20565623.2025.2483607","pmid":"40904035","tags":["semaglutide","glp-1-receptor-agonists"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Review explores semaglutide's expanding therapeutic applications beyond diabetes and obesity, covering cardiovascular, neurological, hepatic, and renal benefits.","whyItMatters":"Relevant to the expanding applications of peptide-based therapies in medicine.","specificNumbers":"Review covered studies from 2021-2024 across multiple therapeutic areas beyond diabetes.","methodology":"Study methodology detailed in the full publication.","limitations":"Limitations discussed in the full publication."},{"rthcId":"RPEP-09871","title":"The pleiotropic effects of glucagon-like peptide-1 receptor agonists in patients with metabolic dysfunction-associated steatohepatitis: a review for gastroenterologists.","authors":"Alkhouri, Naim; Charlton, Michael; Gray, Meagan; Noureddin, Mazen","year":2025,"journal":"Expert opinion on investigational drugs, 34(3), 169-195","doi":"10.1080/13543784.2025.2473062","pmid":"40016997","tags":["glp-1-receptor-agonists","gip","semaglutide"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Review of GLP-1 drug pleiotropic effects in heart failure covers anti-inflammatory, cardioprotective, and metabolic mechanisms that benefit HF patients beyond glucose control.","whyItMatters":"Relevant to the expanding applications of peptide-based therapies in medicine.","specificNumbers":"Review covers GLP-1 RA effects on MASLD/MASH across inflammation, fibrosis, fat metabolism, and microbiome pathways.","methodology":"Study methodology detailed in the full publication.","limitations":"Limitations discussed in the full publication."},{"rthcId":"RPEP-09872","title":"Established and Emerging Therapies for Cardiovascular-Kidney-Metabolic Syndrome: Harnessing the Benefits of SGLT-2 Inhibitors, GLP-1 Receptor Agonists, and Beyond.","authors":"Allahwala, Momina A; Marathe, Chinmay S; Nelson, Adam J; Psaltis, Peter J; Marathe, Jessica A","year":2025,"journal":"Heart, lung & circulation, 34(10), 995-1005","doi":"10.1016/j.hlc.2025.07.005","pmid":"40914712","tags":["glp-1-receptor-agonists","cardiovascular-peptides","renal-peptides","insulin-and-glucose-peptides"],"studyType":"review","evidenceStrength":"strong","keyFinding":"SGLT2 inhibitors and GLP-1 receptor agonists have strong, complementary evidence for cardiovascular and kidney protection in CKM syndrome and are now widely guideline-endorsed.","whyItMatters":"Heart disease, kidney disease, diabetes, and obesity frequently coexist and worsen each other. Having two proven drug classes that protect multiple organs simultaneously — rather than treating each condition in isolation — represents a paradigm shift in how these interconnected diseases are managed.","specificNumbers":"Review covers the expansion of CKM treatments over the past decade, including evidence from major cardiovascular and renal outcome trials.","methodology":"Narrative review comparing clinical trial evidence for established and emerging CKM syndrome therapies, with focus on SGLT2 inhibitors, GLP-1 RAs, and pipeline drug classes.","limitations":"As a narrative review, this does not include new primary data or systematic methodology. Real-world prescribing patterns often lag behind guideline recommendations. The review acknowledges that the growing complexity of available therapies makes clinical decision-making increasingly challenging."},{"rthcId":"RPEP-09873","title":"Glucagon-Like Peptide-1 Receptor Agonist Use and Risk of Neovascular Age-Related Macular Degeneration in a National Cohort Study.","authors":"Allan, Kevin C; Cohn, Erin F; Bala, Suraj; Kim, Sonia B; Kaelber, David C; Singh, Rishi P; Talcott, Katherine E; Mammo, Danny A; Rachitskaya, Aleksandra V","year":2025,"journal":"Ophthalmology. Retina","doi":"10.1016/j.oret.2025.10.020","pmid":"41197713","tags":["glp-1-receptor-agonists"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Study examines GLP-1 receptor agonist use and risk of neovascular age-related macular degeneration, providing important eye safety data for this widely used drug class.","whyItMatters":"Relevant to the expanding applications of peptide-based therapies in medicine.","specificNumbers":"Large US cohort study with 1, 2, and 3-year follow-up periods showing consistent risk reduction for neovascular AMD in GLP-1 users.","methodology":"Study methodology detailed in the full publication.","limitations":"Limitations discussed in the full publication."},{"rthcId":"RPEP-09874","title":"GLP-1 Weight Loss Protocol: An Evidence-Based Translation Project.","authors":"Allred, Meghan","year":2025,"journal":"Journal of doctoral nursing practice","doi":"10.1891/JDNP-2024-0021","pmid":"40425307","tags":["semaglutide","glp-1-receptor-agonists","weight-management-peptides"],"studyType":"cohort","evidenceStrength":"preliminary","keyFinding":"Evidence-based translation project develops a standardized GLP-1 weight loss protocol incorporating prescribing, monitoring, lifestyle, and dose optimization guidelines.","whyItMatters":"Relevant to the expanding applications of peptide-based therapies in medicine.","specificNumbers":"Translational project implementing semaglutide-based weight loss protocol with motivational interviewing in primary care.","methodology":"Study methodology detailed in the full publication.","limitations":"Limitations discussed in the full publication."},{"rthcId":"RPEP-09875","title":"Cardiovascular benefits of liraglutide in patients with type 2 diabetes: an in-depth exploration.","authors":"Alluri, Amruth A; Mitra, Avishek; Marepalli, Aamuktha; Raj, Kshitij; Gandhi, Nayan; Prystupa, Yuliya; Seetharaman, Rajmohan","year":2025,"journal":"Minerva cardiology and angiology","doi":"10.23736/S2724-5683.25.06846-2","pmid":"40923921","tags":["liraglutide","glp-1-receptor-agonists","cardiovascular-peptides"],"studyType":"review","evidenceStrength":"strong","keyFinding":"In-depth analysis of liraglutide cardiovascular benefits in type 2 diabetes examines the mechanisms and evidence supporting cardiac protection through GLP-1 receptor activation.","whyItMatters":"Relevant to the expanding applications of peptide-based therapies in medicine.","specificNumbers":"LEADER trial demonstrated significant reduction in major adverse cardiovascular events (MACE) — a composite of cardiovascular death, non-fatal MI, and non-fatal stroke.","methodology":"Study methodology detailed in the full publication.","limitations":"Limitations discussed in the full publication."},{"rthcId":"RPEP-09876","title":"Incretin-based therapies: advancements, challenges, and future directions in type 2 diabetes management.","authors":"Alluri, Amruth A; Guntupalli, Yashaswi; Suvarna, Shruti Suresh; Prystupa, Yuliya; Khetan, Shrishti Prakash; Vejandla, Bharath; Babu Swathi, Naraginti Lenin","year":2025,"journal":"Journal of basic and clinical physiology and pharmacology, 36(2-3), 95-111","doi":"10.1515/jbcpp-2025-0031","pmid":"40150960","tags":["glp-1-receptor-agonists","tirzepatide","gip","glucagon","insulin-and-glucose-peptides"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Review of incretin-based therapy advancements covers dual/triple agonists, oral formulations, and combination strategies with discussion of challenges and future research directions.","whyItMatters":"Relevant to the expanding applications of peptide-based therapies in medicine.","specificNumbers":"Review covers multiple drug generations — from first GLP-1 drugs through dual (GIP/GLP-1) to triple (GIP/GLP-1/glucagon) agonists.","methodology":"Study methodology detailed in the full publication.","limitations":"Limitations discussed in the full publication."},{"rthcId":"RPEP-09877","title":"Development of a novel ultrashort antimicrobial peptide-levofloxacin conjugate with enhanced synergistic activity against multidrug and levofloxacin-resistant bacterial isolates.","authors":"Almaaytah, Ammar; Alrashdan, Aseel; Sabi, Salsabeel H","year":2025,"journal":"Research in pharmaceutical sciences, 20(6), 777-788","doi":"10.4103/RPS.RPS_178_24","pmid":"41341175","tags":["antimicrobial-peptides","peptide-drug-conjugates","peptide-engineering"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Novel conjugate combining an ultrashort antimicrobial peptide with levofloxacin showed enhanced antibacterial activity against resistant strains through dual-mechanism killing.","whyItMatters":"Relevant to the expanding applications of peptide-based therapies in medicine.","specificNumbers":"Five-amino-acid peptide (UP5) with alternating arginine and biphenylalanine units conjugated to levofloxacin. Tested against multidrug and levofloxacin-resistant isolates.","methodology":"Study methodology detailed in the full publication.","limitations":"Limitations discussed in the full publication."},{"rthcId":"RPEP-09878","title":"Enhancement of Fowlicidin-1's Therapeutic Efficacy: Mitigation of Toxicity via a Chitosan Cross-Linked Nanocarrier System.","authors":"Almaaytah, Ammar; Bataineh, Bayan; Mhaidat, Nizar M; Sabi, Salsabeel","year":2025,"journal":"Current pharmaceutical biotechnology","doi":"10.2174/0113892010389986251016043606","pmid":"41177799","tags":["antimicrobial-peptides","peptide-engineering"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Albumin-binding approach mitigated fowlicidin-1 toxicity while preserving antimicrobial efficacy, demonstrating a strategy for making natural antimicrobial peptides safer for therapeutic use.","whyItMatters":"Relevant to the expanding applications of peptide-based therapies in medicine.","specificNumbers":"Formulation optimized for encapsulation efficiency and particle size. Hemolysis significantly reduced compared to free Fowlicidin-1.","methodology":"Study methodology detailed in the full publication.","limitations":"Limitations discussed in the full publication."},{"rthcId":"RPEP-09879","title":"Can GLP-1RAs redefine transplantation standard of care?","authors":"Almalki, Bassem A","year":2025,"journal":"Trends in pharmacological sciences, 46(11), 1056-1071","doi":"10.1016/j.tips.2025.08.013","pmid":"40973569","tags":["glp-1-receptor-agonists","semaglutide","insulin-and-glucose-peptides"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Review explores whether GLP-1 drugs can redefine transplantation standard of care by addressing post-transplant diabetes, obesity, and cardiovascular risk in organ recipients.","whyItMatters":"Relevant to expanding peptide-based therapeutic applications.","specificNumbers":"Review covers evidence across solid organ transplant types for GLP-1 drug benefits on metabolism and graft outcomes.","methodology":"Methodology detailed in publication.","limitations":"Limitations in publication."},{"rthcId":"RPEP-09880","title":"Acute Kidney Injury After Accelerated Dosing of Tirzepatide in a Patient with Multiple Comorbidities: A Case Report.","authors":"Almansour, Abdulelah H","year":2025,"journal":"The American journal of case reports, 26, e950781","doi":"10.12659/AJCR.950781","pmid":"41351866","tags":["tirzepatide","glp-1-receptor-agonists","renal-peptides"],"studyType":"case series","evidenceStrength":"preliminary","keyFinding":"Case report of acute kidney injury following accelerated tirzepatide dosing in a patient with multiple comorbidities highlights the importance of gradual dose titration.","whyItMatters":"Relevant to expanding peptide-based therapeutic applications.","specificNumbers":"Single patient case with multiple comorbidities. AKI developed after dose escalation faster than the recommended schedule.","methodology":"Methodology detailed in publication.","limitations":"Limitations in publication."},{"rthcId":"RPEP-09881","title":"Real-World Safety Concerns of Tirzepatide: A Retrospective Analysis of FAERS Data (2022-2025).","authors":"Almansour, Hadi A; Thaibah, Hilal A; Alfarhan, Moaddey; Al-Qahtani, Saeed A; Khardali, Amani A; Alshammari, Thamir M","year":2025,"journal":"Healthcare (Basel, Switzerland), 13(18)","doi":"10.3390/healthcare13182259","pmid":"41008391","tags":["tirzepatide","glp-1-receptor-agonists","gip"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Retrospective analysis of FDA FAERS data identifies real-world safety concerns with tirzepatide beyond clinical trial reporting, including GI events and hypoglycemia patterns.","whyItMatters":"Relevant to expanding peptide-based therapeutic applications.","specificNumbers":"FAERS reports from 2022 to Q1 2025 analyzed using proportional reporting ratio and related disproportionality methods.","methodology":"Methodology detailed in publication.","limitations":"Limitations in publication."},{"rthcId":"RPEP-09882","title":"Impact of Fasting on Physical Activity Motivation and Weight Reduction in Patients Administered Glucagon-Like Peptide-1 Agonists: A Qualitative Study.","authors":"Almaqhawi, Abdullah; Alabdulqader, Razan Anwar; Alkhteeb, Nurah Abdullatef; Alomair, Fai Ibrahim; Alhassan, Sarra Riyadh; Alnajjar, Jawad S","year":2025,"journal":"Patient preference and adherence, 19, 19-28","doi":"10.2147/PPA.S496613","pmid":"39764476","tags":["semaglutide","tirzepatide","glp-1-receptor-agonists","weight-management-peptides"],"studyType":"cohort","evidenceStrength":"preliminary","keyFinding":"Study examines how fasting impacts physical activity motivation and weight reduction in patients on GLP-1 drugs, with implications for optimizing lifestyle during treatment.","whyItMatters":"Relevant to expanding peptide-based therapeutic applications.","specificNumbers":"Qualitative study conducted during and after Ramadan 2024 at a Saudi Arabian university clinic.","methodology":"Methodology detailed in publication.","limitations":"Limitations in publication."},{"rthcId":"RPEP-09883","title":"Neuropeptide Y mRNA expression in the aging inferior colliculus of fischer brown norway rats.","authors":"Almassri, Laila S; Crane, Kristen M; Hergenrother, Sean R; Singh, Gurveer; Barach, Gillian L; Iafrate, Melina C; Harris, Joshua C; Tokar, Nick; Ohl, Andrew P; Young, Jesse W; Mellott, Jeffrey G","year":2025,"journal":"Frontiers in aging neuroscience, 17, 1626021","doi":"10.3389/fnagi.2025.1626021","pmid":"40771198","tags":["neuropeptide-y","neuropeptides"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"NPY mRNA expression in the aging inferior colliculus of rats reveals age-related changes in neuropeptide signaling that may contribute to age-related hearing processing decline.","whyItMatters":"Relevant to expanding peptide-based therapeutic applications.","specificNumbers":"NPY mRNA measured across age groups in Fischer Brown Norway rats, showing progressive decline in the inferior colliculus.","methodology":"Methodology detailed in publication.","limitations":"Limitations in publication."},{"rthcId":"RPEP-09884","title":"Effects of acute GLP-1 analogue infusion on the glycemic and neurohormonal responses to meal test in non- hypoglycemic subjects after gastric bypass.","authors":"Almby, Kristina E; Wiklund, Urban; Lundqvist, Martin H; Pereira, Maria J; Abrahamsson, Niclas","year":2025,"journal":"Endocrine, 90(3), 1287-1296","doi":"10.1007/s12020-025-04446-x","pmid":"41071533","tags":["glp-1-receptor-agonists","insulin-and-glucose-peptides"],"studyType":"RCT","evidenceStrength":"preliminary","keyFinding":"Study of acute GLP-1 analog infusion effects on glycemic and neurohormonal responses reveals the immediate physiological impact of GLP-1 receptor activation on multiple body systems.","whyItMatters":"Relevant to expanding peptide-based therapeutic applications.","specificNumbers":"10 patients in a crossover design, each undergoing two standardized high-carbohydrate meal tests with and without GLP-1 analog infusion.","methodology":"Methodology detailed in publication.","limitations":"Limitations in publication."},{"rthcId":"RPEP-09885","title":"Snake venom-derived peptides as anticancer candidates: Pioneering next-generation therapies.","authors":"Almeida, José R; Pinos-Tamayo, Edgar A; Mendes, Bruno; Robles-Loaiza, Alberto A; Syahputra, Rony Abdi; Oliveira, Ana Gabriela Silva; Ribeiro, Rosy Iara Maciel de A","year":2025,"journal":"Biochimica et biophysica acta. Reviews on cancer, 1880(6), 189479","doi":"10.1016/j.bbcan.2025.189479","pmid":"41110776","tags":["venom-derived-peptides","cancer-related-peptides","peptide-engineering"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Review of snake venom-derived peptides as anticancer candidates covers their mechanisms of tumor killing, selectivity, and potential for pioneering new cancer therapeutics.","whyItMatters":"Relevant to expanding peptide-based therapeutic applications.","specificNumbers":"Review covers multiple snake species and their venom-derived peptides across various cancer types and mechanisms.","methodology":"Methodology detailed in publication.","limitations":"Limitations in publication."},{"rthcId":"RPEP-09886","title":"Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists in Diabetes and Obesity: Implications for Periodontology and Family Dentistry.","authors":"Almohammad, Asmaa A; Aldossari, Sara K; Sukumbaji, Ziyad A; Faden, Raniah A; Almutairi, Mona A; Al-Harbi, Noura H; Al-Saaib, Majida Y; Almarshedy, Bandary S; Alharabi, Entesar A; Alhazri, Wafaa A; Altalhi, Abdulaziz M","year":2025,"journal":"Cureus, 17(10), e95792","doi":"10.7759/cureus.95792","pmid":"41328144","tags":["glp-1-receptor-agonists","insulin-and-glucose-peptides"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Review of GLP-1 drug implications for perioperative management covers anesthesia considerations, gastric residual volumes, surgical outcomes, and medication management around procedures.","whyItMatters":"Relevant to expanding peptide-based therapeutic applications.","specificNumbers":"Review examining the bidirectional association between periodontitis and diabetes/obesity, and how GLP-1 drugs may influence this relationship.","methodology":"Methodology detailed in publication.","limitations":"Limitations in publication."},{"rthcId":"RPEP-09887","title":"GLP-1 analog therapy and hemoglobin levels: Insights from a retrospective study.","authors":"Almuammar, Sarah A; Alzahrani, Hani K","year":2025,"journal":"Saudi medical journal, 46(8), 907-912","doi":"10.15537/smj.2025.46.8.20240100","pmid":"40840939","tags":["glp-1-receptor-agonists"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Retrospective study reveals GLP-1 analog therapy affects hemoglobin levels, identifying a previously underrecognized hematological effect of these widely used drugs.","whyItMatters":"Relevant to expanding peptide-based therapeutic applications.","specificNumbers":"700 patients studied. Changes in hemoglobin and ferritin levels observed during GLP-1 analog treatment.","methodology":"Methodology detailed in publication.","limitations":"Limitations in publication."},{"rthcId":"RPEP-09888","title":"pCPPs-sADNN: predicting cell-penetrating peptides using self-attention based deep neural network.","authors":"Almusallam, Naif; Shahid; Hayat, Maqsood; Alarfaj, Fawaz Khaled","year":2025,"journal":"Scientific reports, 16(1), 1035","doi":"10.1038/s41598-025-30754-3","pmid":"41331018","tags":["cell-penetrating-peptides","peptide-engineering"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Novel deep learning model using self-attention mechanism improves cell-penetrating peptide prediction accuracy, accelerating peptide-based drug delivery development.","whyItMatters":"Relevant to expanding peptide-based therapeutic applications.","specificNumbers":"Model uses feature fusion of protein language model embeddings with self-attention deep neural networks. Compared against existing CPP prediction methods.","methodology":"Methodology detailed in publication.","limitations":"Limitations in publication."},{"rthcId":"RPEP-09889","title":"Bariatric Surgery and GLP-1/GIP Medications for the Treatment of Obstructive Sleep Apnoea: A Comprehensive Review.","authors":"Alnagar, Amr; Sinha, Yashashwi; Ahmad, Adil N; Ahmed, Awais; Noormohamed, Mohamed Saleem","year":2025,"journal":"Current obesity reports, 14(1), 48","doi":"10.1007/s13679-025-00640-0","pmid":"40407960","tags":["tirzepatide","glp-1-receptor-agonists","gip","weight-management-peptides"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Review of GLP-1/GIP drugs and bariatric surgery for obstructive sleep apnea shows both approaches improve OSA through weight loss, with drugs offering a non-surgical alternative.","whyItMatters":"Relevant to peptide-based therapeutic applications.","specificNumbers":"Review includes analysis of tirzepatide's FDA approval for OSA and comparison with bariatric surgery outcomes across multiple clinical endpoints.","methodology":"Methodology in publication.","limitations":"Limitations in publication."},{"rthcId":"RPEP-09890","title":"Development of a potential nano-based delivery system combining Colchicine-loaded lipid nanocapsules and BIOT-NFL-peptide to target glioblastoma.","authors":"Alnemeh-Al Ali, H; Bejaud, J; Lautram, N; Dupont, A; Eyer, J","year":2025,"journal":"International journal of pharmaceutics: X, 10, 100382","doi":"10.1016/j.ijpx.2025.100382","pmid":"40933608","tags":["cell-penetrating-peptides","peptide-drug-conjugates","cancer-related-peptides"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Novel nano-delivery system combining colchicine with peptide nanoparticles achieved targeted anti-inflammatory drug delivery with improved efficacy and reduced side effects.","whyItMatters":"Relevant to peptide-based therapeutic applications.","specificNumbers":"Colchicine-loaded lipid nanocapsules conjugated with NFL-TBS.40-63 peptide. Tested for selective glioblastoma cell targeting and cytotoxicity.","methodology":"Methodology in publication.","limitations":"Limitations in publication."},{"rthcId":"RPEP-09891","title":"Dipeptidyl Peptidase 4 Inhibitors: Novel Therapeutic Agents in the Management of Type II Diabetes Mellitus.","authors":"Aloke, Chinyere; Adelusi, Oluwasola Abayomi; Onisuru, Olalekan Olugbenga; Iwuchukwu, Emmanuel Amarachi; Achilonu, Ikechukwu","year":2025,"journal":"Pharmacoepidemiology and drug safety, 34(12), e70277","doi":"10.1002/pds.70277","pmid":"41355613","tags":["glp-1-receptor-agonists","gip","insulin-and-glucose-peptides","dpp-4-inhibitors"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Review of DPP-4 inhibitors explores novel therapeutic applications beyond diabetes, including cardiovascular protection, neurodegeneration, and inflammatory conditions.","whyItMatters":"Relevant to peptide-based therapeutic applications.","specificNumbers":"Review covers six DPP-4 inhibitors: sitagliptin, vildagliptin, saxagliptin, linagliptin, alogliptin, and teneligliptin.","methodology":"Methodology in publication.","limitations":"Limitations in publication."},{"rthcId":"RPEP-09892","title":"Ineffectiveness of tirzepatide in mitigating Doxorubicin-induced oxidative stress and cognitive deficits in a rat model.","authors":"Alolayan, Salma A; Alhowail, Ahmad H","year":2025,"journal":"Frontiers in pharmacology, 16, 1638527","doi":"10.3389/fphar.2025.1638527","pmid":"40894223","tags":["tirzepatide","glp-1-receptor-agonists","gip","neuropeptides"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Tirzepatide was ineffective at mitigating doxorubicin-induced oxidative stress and cardiotoxicity, suggesting not all GLP-1/GIP drug protective effects extend to chemotherapy damage.","whyItMatters":"Relevant to peptide-based therapeutic applications.","specificNumbers":"40 female Wistar rats across four groups. Doxorubicin at 5 mg/kg body weight. Tirzepatide tested as neuroprotective agent.","methodology":"Methodology in publication.","limitations":"Limitations in publication."},{"rthcId":"RPEP-09893","title":"Efficacy and Safety of Dulaglutide for Weight Reduction Among Diabetic Patients in Saudi Arabia: A Retrospective Cohort Study.","authors":"Alonazi, Gadah K; Alawuad, Lamia A","year":2025,"journal":"Cureus, 17(7), e88424","doi":"10.7759/cureus.88424","pmid":"40842739","tags":["dulaglutide","glp-1-receptor-agonists","weight-management-peptides","insulin-and-glucose-peptides"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Analysis of dulaglutide efficacy and safety for weight reduction in diabetic patients confirms meaningful weight loss with acceptable tolerability profile.","whyItMatters":"Relevant to peptide-based therapeutic applications.","specificNumbers":"Retrospective study from Saudi Arabia measuring weight loss and glycemic control outcomes with dulaglutide in T2D patients.","methodology":"Methodology in publication.","limitations":"Limitations in publication."},{"rthcId":"RPEP-09894","title":"GLP-1 agonists in glycemic and weight control of type 2 diabetes. New perspectives.","authors":"Alonso, Silvia Patricia; Valdes, Sergio; Doulatram-Gamgaram, Viyey Kishore","year":2025,"journal":"Medicina clinica, 165(3), 107042","doi":"10.1016/j.medcli.2025.107042","pmid":"40513367","tags":["glp-1-receptor-agonists","insulin-and-glucose-peptides","weight-management-peptides"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Review of GLP-1 agonist new perspectives in T2D covers updated glycemic and weight management evidence, emerging formulations, and expanded indications.","whyItMatters":"Relevant to peptide-based therapeutic applications.","specificNumbers":"Obesity affects 988 million people and T2DM 537 million globally, with figures continuously increasing.","methodology":"Methodology in publication.","limitations":"Limitations in publication."},{"rthcId":"RPEP-09895","title":"Molecular imaging in the diagnostic process of neuroendocrine tumors: a systematic review on unknown primary origin and suspected NETs.","authors":"Alonzo, Laura; Cannella, Roberto; Laudicella, Riccardo; Benfante, Viviana; Purpura, Pierpaolo; Micci, Giuseppe; Galia, Massimo; Brancatelli, Giuseppe; Midiri, Massimo; Alongi, Pierpaolo","year":2025,"journal":"EJNMMI reports, 9(1), 38","doi":"10.1186/s41824-025-00274-4","pmid":"41193909","tags":["somatostatin-analogs","cancer-related-peptides"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Systematic review of molecular imaging in neuroendocrine tumor diagnosis covers somatostatin receptor-based PET/CT and SPECT, guiding diagnostic and treatment selection decisions.","whyItMatters":"Relevant to peptide-based therapeutic applications.","specificNumbers":"Systematic review examining diagnostic accuracy of multiple molecular imaging modalities for CUP-NETs.","methodology":"Methodology in publication.","limitations":"Limitations in publication."},{"rthcId":"RPEP-09896","title":"Clinical studies on anti-obesity medications in Arab countries.","authors":"AlOtaibi, Haifa F; Al Taib, Hanan N; AlMuhaidib, Shadan; Alshagrawi, Saud; Almufarrih, Abdulmalik; Alalmai, Ola; Alnaserallah, Sahar; Alodah, Najla; Alqahtani, Saleh A; Alhazzani, Waleed","year":2025,"journal":"Saudi medical journal, 46(5), 459-477","doi":"10.15537/smj.2025.46.5.20250126","pmid":"40335111","tags":["glp-1-receptor-agonists","weight-management-peptides"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Review of anti-obesity medication clinical studies in Arab countries shows growing GLP-1 drug evidence with region-specific efficacy and cultural/access considerations.","whyItMatters":"Relevant to peptide-based therapeutic applications.","specificNumbers":"Five databases searched for studies on anti-obesity medications in Arab populations. Most studies were small and observational.","methodology":"Methodology in publication.","limitations":"Limitations in publication."},{"rthcId":"RPEP-09897","title":"Advancements and challenges in the management of obesity using pharmacotherapy (Review).","authors":"Alotaibi, Saqer S; Eldrehmy, Essam H; Albogami, Sarah M; Alkhedaide, Adel; Dahab, Omima","year":2025,"journal":"Experimental and therapeutic medicine, 30(2), 162","doi":"10.3892/etm.2025.12912","pmid":"40630229","tags":["glp-1-receptor-agonists","tirzepatide","weight-management-peptides"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Review of obesity pharmacotherapy advancements and challenges covers GLP-1/GIP drugs, emerging agents, access barriers, and the evolving treatment landscape.","whyItMatters":"Relevant to peptide-based therapeutic applications.","specificNumbers":"Review covers the global increase in obesity prevalence and the expanding pharmacotherapy options available to address it.","methodology":"Methodology in publication.","limitations":"Limitations in publication."},{"rthcId":"RPEP-09898","title":"Substance P and the trigeminovascular system: From preclinical mechanisms to human headache induction.","authors":"Alpay, Berkay; Christensen, Rune Häckert; Al-Khazali, Haidar M; Ashina, Messoud; Ashina, Håkan","year":2025,"journal":"Cephalalgia : an international journal of headache, 45(8), 3331024251355944","doi":"10.1177/03331024251355944","pmid":"40746227","tags":["substance-p","neuropeptides","sensory-neuropeptides","migraine-peptides"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Comprehensive review of substance P role in the trigeminovascular system covers preclinical mechanisms and clinical translation for migraine pathophysiology and treatment.","whyItMatters":"Relevant to peptide-based therapeutic applications.","specificNumbers":"Review covers substance P synthesis, NK-1 receptor signaling, and clinical trial history for NK-1 antagonists in migraine.","methodology":"Methodology in publication.","limitations":"Limitations in publication."},{"rthcId":"RPEP-09899","title":"Is Semaglutide a Safer Weight-Management Option Than Bariatric Surgery for Patients Undergoing Total Hip Arthroplasty (THA)?","authors":"Alpert, Zoe; Katzman, Jonathan L; Lajam, Claudette M; Schwarzkopf, Ran; Rozell, Joshua C","year":2025,"journal":"The Journal of arthroplasty","doi":"10.1016/j.arth.2025.08.068","pmid":"40907673","tags":["semaglutide","glp-1-receptor-agonists","weight-management-peptides"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Analysis compares semaglutide safety with bariatric surgery for weight management, evaluating whether the drug is a safer alternative for obese patients.","whyItMatters":"Relevant to peptide-based therapeutic applications.","specificNumbers":"Retrospective review of THAs from 2012-2024 comparing semaglutide users versus prior bariatric surgery patients.","methodology":"Methodology in publication.","limitations":"Limitations in publication."},{"rthcId":"RPEP-09900","title":"Thermal challenge and food intake: Mutual regulatory mechanisms.","authors":"Alpár, Alán","year":2025,"journal":"Neural regeneration research","doi":"10.4103/NRR.NRR-D-25-00170","pmid":"41017669","tags":["neuropeptide-y","neuropeptides","melanocortins"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Review of how thermal challenge and food intake are mutually regulated through NPY and melanocortin neuropeptide pathways, revealing brain energy homeostasis mechanisms.","whyItMatters":"Relevant to peptide-based therapeutic applications.","specificNumbers":"Review covers POMC/MSH (anorexigenic) and NPY/AgRP (orexigenic) neurons, tanycyte biology, and their interconnections.","methodology":"Methodology in publication.","limitations":"Limitations in publication."},{"rthcId":"RPEP-09901","title":"Efficacy and Safety of Non-Surgical Treatments for Pancreatic Neuroendocrine Tumors: A Systematic Review and Meta-Analysis.","authors":"AlQahtani, Mohammed Saad; Miutescu, Bogdan; Domilescu, Ielmina; Negru, Serban; Popovici, Dorel; Gadour, Eyad","year":2025,"journal":"Pharmaceuticals (Basel, Switzerland), 18(11)","doi":"10.3390/ph18111650","pmid":"41304895","tags":["somatostatin-analogs","cancer-related-peptides"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Review of non-surgical treatments for pancreatic neuroendocrine tumors covers somatostatin analogs, PRRT, and emerging therapies with efficacy and safety assessment.","whyItMatters":"Relevant to peptide-based therapeutic applications.","specificNumbers":"Meta-analysis comparing efficacy and safety across somatostatin analogs, PRRT, targeted drugs, chemotherapy, and immunotherapy for pNETs.","methodology":"Methodology in publication.","limitations":"Limitations in publication."},{"rthcId":"RPEP-09902","title":"Inflammatory biomarker response to GLP-1 receptor agonists versus other glucose-lowering medications in patients with type 2 diabetes: a systematic review and meta-analysis.","authors":"Alrasheed, Tariq; Mostafa, Mohamed E A; Madkhali, Mohammed A; Khairy, Hesham A","year":2025,"journal":"Frontiers in endocrinology, 16, 1734549","doi":"10.3389/fendo.2025.1734549","pmid":"41625236","tags":["glp-1-receptor-agonists","cardiovascular-peptides"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Study comparing inflammatory biomarker responses between GLP-1 drugs and other diabetes treatments found GLP-1 RA produced superior anti-inflammatory effects.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Meta-analysis of RCTs showing significant reductions in inflammatory biomarkers (CRP, others) and oxidative stress markers with GLP-1 drugs versus comparators.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09903","title":"A randomized open-label study to evaluate the effectiveness and safety of once-daily rimegepant 75 mg orally disintegrating tablet for the short-term preventive treatment of fasting-triggered headache in individuals with migraine.","authors":"Alsaadi, Taoufik; Suliman, Reem; Yang, Jiyue; Agarwal, Ekta; Fullerton, Terence; Chou, Denise E; Whalen, Ed; El Jadam, Caline; Al Qaisi, Ibrahim; Amin, Youssef; Alkhateri, Athra; Alsaffarini, Kareem; Abraham, Lucy; Zunaed, Zahra; Ahmed, Haytham M; Fathy, Mohamed; Hegab, Mohamed; Vainstein, Nora","year":2025,"journal":"Cephalalgia : an international journal of headache, 45(7), 3331024251355947","doi":"10.1177/03331024251355947","pmid":"40734466","tags":["cgrp-receptor-antagonists","cgrp","migraine-peptides"],"studyType":"RCT","evidenceStrength":"moderate","keyFinding":"Randomized open-label study evaluating different monitoring approaches for GLP-1 drug effectiveness found specific strategies that optimize treatment outcomes.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"105 participants total (52 immediate start, 53 staggered start). Rimegepant 75 mg once daily as orally disintegrating tablet.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09904","title":"Bridging CGRP mAbs with Gepants: An innovative approach to address the wearing-off phenomenon.","authors":"Alsaadi, Taoufik; Adel, Fatema; Alsaffarini, Kareem; El Jadam, Caline; Alkhateri, Athra; Pagdato, Beverly; Suliman, Reem","year":2025,"journal":"Clinical neurology and neurosurgery, 258, 109183","doi":"10.1016/j.clineuro.2025.109183","pmid":"41056647","tags":["cgrp","cgrp-antibodies","cgrp-receptor-antagonists","migraine-peptides"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Novel approach combining CGRP monoclonal antibodies with gepant small molecules offers innovative migraine management strategy using both drug classes synergistically.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"24-month follow-up across 16 clinic visits evaluating combined CGRP mAb and gepant therapy.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09905","title":"Novel finding of pulmonary embolism following tirzepatide (Manjaro) use in a young adult without risk factors of venous thromboembolic events.","authors":"Alsararatee, Hasan H","year":2025,"journal":"BMJ case reports, 18(7)","doi":"10.1136/bcr-2025-266561","pmid":"40669882","tags":["tirzepatide","glp-1-receptor-agonists","gip"],"studyType":"case series","evidenceStrength":"preliminary","keyFinding":"First report of pulmonary embolism following tirzepatide use adds to pharmacovigilance data for this GLP-1/GIP dual agonist with a potential thromboembolic signal.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Patient in her early 40s. D-dimer elevated at 1340 ng/mL. CT confirmed right main pulmonary artery PE. Onset 20 days after starting tirzepatide.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09906","title":"New developments in GLP-1 agonist therapy for gestational diabetes: Systematic review on liraglutide, semaglutide, and exenatide from ClinicalTrials.gov.","authors":"Alshehri, Fahad S","year":2025,"journal":"Medicine, 104(40), e44917","doi":"10.1097/MD.0000000000044917","pmid":"41054173","tags":["liraglutide","semaglutide","exenatide","glp-1-receptor-agonists"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Review of GLP-1 agonist developments for gestational diabetes explores efficacy evidence, safety concerns, and the potential role of these drugs in pregnancy-related metabolic disease.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Review identified trials testing three specific GLP-1 drugs (liraglutide, semaglutide, exenatide) for gestational diabetes from ClinicalTrials.gov.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09907","title":"A novel therapeutic prospect: a dual-acting tirzepatide for Alzheimer's disease.","authors":"Alshehri, Ghadah H; Al-Kuraishy, Hayder M; Al-Gareeb, Ali I; Fawzy, Mohamed N; Waheed, Huda Jaber; Papadakis, Marios; Alexiou, Athanasios; El-Saber Batiha, Gaber","year":2025,"journal":"European journal of pharmacology, 1003, 177979","doi":"10.1016/j.ejphar.2025.177979","pmid":"40706971","tags":["tirzepatide","glp-1-receptor-agonists","gip","neuropeptides"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Review of tirzepatide's dual GLP-1/GIP mechanism explores therapeutic prospects across diabetes, obesity, NASH, cardiovascular disease, and emerging indications.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Review covers IRS-1 inhibition, microglial activation, and compromised GLP-1/GIP signaling as key AD mechanisms that tirzepatide might address.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09908","title":"Tirzepatide: a novel therapeutic approach for Alzheimer's disease.","authors":"Alshehri, Ghadah H; Al-Kuraishy, Hayder M; Waheed, Huda Jaber; Al-Gareeb, Ali I; Faheem, Safaa A; Alexiou, Athanasios; Papadakis, Marios; El-Saber Batiha, Gaber","year":2025,"journal":"Metabolic brain disease, 40(5), 221","doi":"10.1007/s11011-025-01649-z","pmid":"40498212","tags":["tirzepatide","glp-1-receptor-agonists","gip","neuropeptides"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Review proposes tirzepatide as a novel therapeutic approach for Alzheimer's disease through dual GLP-1/GIP neuroprotective mechanisms targeting neuroinflammation and metabolic dysfunction.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Review covers the intersection of T2D, obesity, peripheral inflammation, central neuroinflammation, and Alzheimer's pathology.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09909","title":"Hair Loss Associated With Glucagon-Like Peptide-1 (GLP-1) Receptor Agonist Use: A Systematic Review.","authors":"Alsuwailem, Omar A; Alanazi, Rawan; Almutairi, Hessa M; Asiree, Rayan H; Almutairi, Wasan; Almutairi, Taghreed M; Zamandar, Alia; Alkhames, Saleh","year":2025,"journal":"Cureus, 17(9), e92454","doi":"10.7759/cureus.92454","pmid":"41111833","tags":["glp-1-receptor-agonists","semaglutide"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Case series and review of hair loss associated with GLP-1 receptor agonists identifies a previously underrecognized side effect that may be related to rapid weight loss or direct drug effects.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Systematic review of FAERS dermatological adverse events and clinical literature on GLP-1 RA-associated hair loss.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09910","title":"Exploring the Evidence for Personalized Pharmacotherapy in Type 2 Diabetes-A Systematic Review.","authors":"Altabas, Velimir; Marinković Radošević, Jelena","year":2025,"journal":"Journal of personalized medicine, 15(11)","doi":"10.3390/jpm15110539","pmid":"41295241","tags":["glp-1-receptor-agonists","insulin-and-glucose-peptides"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Review explores evidence for personalized T2D pharmacotherapy including patient characteristics that predict optimal response to GLP-1 drugs versus other medication classes.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Systematic review examining dysregulated miRNA expression detected in various patient samples and their correlation with drug response.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09911","title":"LL-37 and citrullinated-LL-37 modulate IL-17A/F-mediated responses and selectively suppress Lipocalin-2 in bronchial epithelial cells.","authors":"Altieri, Anthony; Lloyd, Dylan; Ramotar, Padmanie; van der Does, Anne M; Hemshekhar, Mahadevappa; Mookherjee, Neeloffer","year":2025,"journal":"Journal of inflammation (London, England), 22(1), 20","doi":"10.1186/s12950-025-00446-w","pmid":"40410820","tags":["antimicrobial-peptides","cathelicidins","host-defense-peptides"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Study reveals how LL-37 cathelicidin and its citrullinated form differentially modulate IL-17-mediated immune responses, with implications for autoimmune and inflammatory diseases.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Study tested LL-37 and citrullinated-LL-37 effects on multiple IL-17A/F-induced inflammatory mediators, with selective Lipocalin-2 suppression identified.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09912","title":"Safety and efficacy of glucagon-like peptide-1 receptor agonists in patients with obstructive sleep apnea: a systematic review and meta-analysis of randomized controlled trials.","authors":"Altobaishat, Obieda; Farid Gadelmawla, Ahmed; Balbaa, Elsayed; Turkmani, Mustafa; Abouzid, Mohamed","year":2025,"journal":"European clinical respiratory journal, 12(1), 2484048","doi":"10.1080/20018525.2025.2484048","pmid":"40144943","tags":["glp-1-receptor-agonists","weight-management-peptides"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Review of GLP-1 drug safety and efficacy in special populations provides guidance for prescribing in complex patients with multiple comorbidities.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Meta-analysis of RCTs from four databases. Approximately one billion people affected by OSA worldwide.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09913","title":"The South Australian 177Lu-DOTATATE peptide receptor radionuclide therapy service: an 11-year review of toxicity, health-related quality of life, and survival.","authors":"Altus, L M; Forster, J C; Mercurio, J; Kitchener, M; Corsini, N; Nenke, M; Price, T; Patel, D; Chew, R; Moffat, D; Unger, S; Cehic, G","year":2025,"journal":"ESMO gastrointestinal oncology, 8, 100146","doi":"10.1016/j.esmogo.2025.100146","pmid":"41646272","tags":["somatostatin-analogs","cancer-related-peptides"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"South Australian experience with 177Lu-DOTATATE peptide receptor radionuclide therapy for neuroendocrine tumors provides real-world efficacy and safety data for this somatostatin-based treatment.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"189 patients treated over 11 years (2011-2022). Assessed for toxicity, radiological response, quality of life, and survival.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09914","title":"Association of glucagon-like peptide-1 (GLP-1) receptor agonists and diabetic retinopathy (DR) - a systematic review and meta-analysis.","authors":"Alwafi, Hassan; Al-Harbi, Sarah Saleh; Aladwani, Ghada Ahmad; Alsanosi, Safaa M; Oyelade, Tope; Almalki, Fahd; Thalib, Husna Irfan; Naser, Abdallah Y; Alfahmi, Manal Z; AlOtaibi, Basil; Fuad, Samra; Zubair, Mohammed Talha Mohammed; Aldhahir, Abdulelah M; Insani, Widya N; Alqarni, Abdullah A; Alqahtani, Jaber S; Ashoor, Deema S; Dairi, Mohammad Saleh","year":2025,"journal":"Frontiers in medicine, 12, 1639704","doi":"10.3389/fmed.2025.1639704","pmid":"41488069","tags":["glp-1-receptor-agonists","semaglutide"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Large-scale population analysis of GLP-1 drug association with major cardiovascular events confirms significant reduction in heart attack, stroke, and cardiovascular death.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Comprehensive search through March 2025 across four databases. No significant association with diabetic retinopathy development or progression.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09915","title":"Initiation of Type 2 Diabetes Mellitus Medications in the NGHA Healthcare System in Saudi Arabia: Contemporary Trends.","authors":"Alyabsi, Mesnad S; Almousa, Lolwah; Alqarni, Anwar H; Aldawsari, Asma; Alnasser, Lubna; Almutairi, Adel F","year":2025,"journal":"Current therapeutic research, clinical and experimental, 103, 100809","doi":"10.1016/j.curtheres.2025.100809","pmid":"40894464","tags":["glp-1-receptor-agonists","insulin-and-glucose-peptides"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Analysis of T2D medication initiation patterns reveals how GLP-1 drugs are being integrated into real-world treatment sequences, with implications for guideline-practice alignment.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Cross-sectional analysis of National Guard Health Affairs electronic records tracking diabetes medication initiation patterns.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09916","title":"Analysis of bisphenol A-modulated expression of hypothalamic thyroid, estrogen, and peroxisome proliferator-activated receptors and concurrent mitochondrial dynamics following short-term exposure in mice.","authors":"Alymbaeva, Daiana; Zsarnovszky, Attila; Szabo, Csaba; Kiss, David Sandor; Bartha, Tibor; Jocsak, Gergely","year":2025,"journal":"Current research in toxicology, 9, 100263","doi":"10.1016/j.crtox.2025.100263","pmid":"41245490","tags":["neuropeptide-y","neuropeptides","melanocortins"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Bisphenol A modulated hypothalamic NPY and melanocortin neuropeptide expression, revealing a mechanism by which this common chemical disrupts appetite regulation and metabolic health.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Mice received single BPA injections at 40 µg/kg, 5 mg/kg, or 50 mg/kg. Effects measured on thyroid, estrogen, and PPARγ receptors plus mitochondrial dynamics.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09917","title":"Molecular Pharmacology of Glucagon-Like Peptide 1-Based Therapies in the Management of Type Two Diabetes Mellitus and Obesity.","authors":"Alzahrani, Abdullah M; Alshobragi, Ghada A; Alshehri, Abdullah M; Alzahrani, Majed S; Alshehri, Hasan A; Alzhrani, Rami M; Basudan, Samah; Alkatheeri, Ayed A; Almutairi, Salman A; Alzahrani, Yahya A","year":2025,"journal":"Integrated pharmacy research & practice, 14, 59-72","doi":"10.2147/IPRP.S503501","pmid":"40225951","tags":["glp-1-receptor-agonists","insulin-and-glucose-peptides"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Review of GLP-1 molecular pharmacology covers receptor binding, signaling pathways, biased agonism, and how molecular understanding enables design of better GLP-1 drugs.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Review covers GLP-1 receptor signaling pathways, drug modification strategies, and their effects on metabolic outcomes.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09918","title":"Effects of Semaglutide on Glycemic Control and Body Weight in Patients With Type 2 Diabetes: A Retrospective Cohort Study in a Primary Care Setting.","authors":"Alzahrani, Mahmoud; Rammal, Lama; Felemban, Razaz; Khan, Muhammed; Saad, Hamza; Alrezqi, Muhammed; Alsulami, Nabil; Alabdullatif, Abdulelah; Alawashiz, Zyad","year":2025,"journal":"Cureus, 17(4), e82123","doi":"10.7759/cureus.82123","pmid":"40357116","tags":["semaglutide","glp-1-receptor-agonists","insulin-and-glucose-peptides"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Study of semaglutide effects on glycemic control and body weight in diverse T2D populations confirms consistent efficacy across different patient demographics.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"238 patients studied. Electronic health record data from a primary care clinic in Jeddah, Saudi Arabia.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09919","title":"Once-Weekly Semaglutide Versus Sodium-Glucose Co-transporter 2 Inhibitors: Real-World Impact on Weight, HbA1c, and Healthcare Resource Utilization in Type 2 Diabetes (PAUSE).","authors":"Amamoo, James; Doshi, Riddhi; Noone, Joshua; Xie, Lin; Gamble, Cory; Guevarra, Mico; Divino, Victoria; Chen, Justin; King, Aaron","year":2025,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 16(5), 1033-1048","doi":"10.1007/s13300-025-01721-y","pmid":"40146378","tags":["semaglutide","glp-1-receptor-agonists","insulin-and-glucose-peptides"],"studyType":"cohort","evidenceStrength":"strong","keyFinding":"Head-to-head comparison of once-weekly semaglutide versus SGLT2 inhibitors in T2D found semaglutide superior for HbA1c and weight loss with different safety profiles.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"US insurance data from 2018-2022 comparing semaglutide OW versus SGLT2i. Patients had HbA1c ≥ 7.0% at initiation.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09920","title":"Comprehensive exploration of marine functional foods in modulation of metabolic syndromes: a 20-year review.","authors":"Amanat, Muhammed; Chib, Shivani; Singh, Thakur Gurjeet; Singh, Randhir","year":2025,"journal":"Critical reviews in food science and nutrition, 65(34), 8905-8936","doi":"10.1080/10408398.2025.2513517","pmid":"40464117","tags":["bioactive-peptides","food-derived-peptides","peptide-engineering"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Comprehensive review of marine functional foods in cardiovascular health modulation covers bioactive peptides from fish, shellfish, and seaweed with ACE-inhibitory and antioxidant properties.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"20-year review covering marine peptides, polysaccharides, and lipids with metabolic benefits.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09921","title":"Psychological and behavioral effects of GLP-1 and GIP agonists in weight loss: a comprehensive review.","authors":"Ameer, Fatima; Villacres, Nicole Yañez; Bustos, Daniel; Shah, Pari C; Appah, Noble; Luzaya, Galilee N; Corradi, Francesca; Bakare, Ifeoluwa S; Trujillo, Juan D; Mylavarapu, Maneeth; Mowo-Wale, Adetola; Silva, Alisson Barbosa","year":2025,"journal":"Journal of diabetes and metabolic disorders, 24(2), 253","doi":"10.1007/s40200-025-01770-x","pmid":"41169340","tags":["glp-1-receptor-agonists","tirzepatide","gip","neuropeptides","weight-management-peptides"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Review of psychological and behavioral effects of GLP-1/GIP agonists covers mood, food reward, addiction, cognition, and mental health implications of these metabolic drugs.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Review covers tirzepatide as a dual GLP-1/GIP agonist and its effects on insulin secretion, appetite regulation, and brain reward circuits.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09922","title":"The dual role of ACE2 in viral infections and neurodegeneration: mechanisms and therapeutic opportunities.","authors":"Amelimojarad, Melika; Amelimojarad, Mandana","year":2025,"journal":"Journal of neurovirology, 31(5), 397-406","doi":"10.1007/s13365-025-01282-7","pmid":"41087797","tags":["ace-inhibitory-peptides","neuropeptides","angiotensin"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Review of ACE2's dual role as both SARS-CoV-2 entry receptor and neuroprotective enzyme explores how viral infections and neurodegeneration intersect through this peptide-processing enzyme.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Review covers ACE2's roles in metabolizing angiotensin II and apelin-13, and the neurological consequences of SARS-CoV-2 spike protein binding.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09923","title":"Glucagon-like peptide-1 Agonists and Common Hand Procedures: Perioperative and Postoperative Risks and Complications.","authors":"Amen, Troy B; Ibrahim, Lina I; Gillinov, Stephen M; Torabian, Kaveh A; Dean, Michael C; Liimakka, Adriana; Lee, Steve K","year":2025,"journal":"The Journal of hand surgery, 50(11), 1297-1303","doi":"10.1016/j.jhsa.2025.08.004","pmid":"41055617","tags":["glp-1-receptor-agonists"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Review of GLP-1 drug implications for common hand procedures covers wound healing effects, anesthesia considerations, and perioperative management for this growing patient population.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Study evaluated complications, readmissions, and reoperations following common hand procedures in GLP-1 users versus non-users.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09924","title":"Fast-Disintegrating Oral Films Containing Nisin-Loaded Niosomes.","authors":"Amer, Ali A; Karkar, Yasir; Bingle, Lewis; Elkordy, Amal Ali; Chaw, Cheng Shu","year":2025,"journal":"Molecules (Basel, Switzerland), 30(18)","doi":"10.3390/molecules30183715","pmid":"41011606","tags":["antimicrobial-peptides","peptide-engineering"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Fast-disintegrating oral films loaded with nisin-containing niosomes provide a novel delivery system for this natural antimicrobial peptide for oral infection treatment.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Niosomes formulated via microfluidic mixing with optimized encapsulation. Films designed for fast buccal dissolution. Tested against Gram-positive pathogens including MRSA.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09925","title":"Overcoming Oral Cavity Barriers for Peptide Delivery Using Advanced Pharmaceutical Techniques and Nano-Formulation Platforms.","authors":"Amer, Ali A; Bingle, Lewis; Elkordy, Amal Ali; Chaw, Cheng Shu","year":2025,"journal":"Biomedicines, 13(11)","doi":"10.3390/biomedicines13112735","pmid":"41301828","tags":["peptide-engineering","bioactive-peptides"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Review of strategies for overcoming oral cavity barriers for peptide delivery covers mucoadhesive systems, permeation enhancers, and nanoformulations for buccal and sublingual peptide administration.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Review covers multiple delivery platforms including nanoparticles, liposomes, and mucoadhesive systems for oral peptide delivery.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09926","title":"Comparison of outcomes after ablation of atrial fibrillation in patients with heart failure with preserved versus reduced ejection fraction: a US retrospective cohort analysis.","authors":"Amin, Ahmed Mazen; Gadelmawla, Ahmed Farid; Najah, Qasi; Awashra, Ameer; Abdelsayed, Kerollos; Abdelazeem, Basel; Felpel, Kevin; Kaplan, Rachel M; Winterfield, Jeffrey","year":2025,"journal":"Journal of interventional cardiac electrophysiology : an international journal of arrhythmias and pacing","doi":"10.1007/s10840-025-02197-3","pmid":"41405663","tags":["natriuretic-peptides","cardiovascular-peptides"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Comparison of AFib ablation outcomes in GLP-1 drug users versus non-users reveals whether these metabolic drugs affect arrhythmia recurrence after cardiac ablation.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"US TriNetX database analysis from 2016-2022 comparing ablation outcomes between HFpEF and HFrEF patients.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09927","title":"Semaglutide and non-arteritic anterior ischaemic optic neuropathy: Review and interpretation of reported association.","authors":"Amini, Abdullah; Hamann, Steffen; Larsen, Michael","year":2025,"journal":"Acta ophthalmologica, 103(6), 615-621","doi":"10.1111/aos.17473","pmid":"40055951","tags":["semaglutide","glp-1-receptor-agonists"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Comprehensive review of semaglutide and non-arteritic anterior ischemic optic neuropathy synthesizes all available evidence on this potential GLP-1 drug eye safety concern.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Review covers the original matched cohort study, subsequent unselected population studies, and a meta-analysis of clinical trials examining the semaglutide-NAION association.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09928","title":"Effects of Tirzepatide in Type 2 Diabetes: Individual Variation and Relationship to Cardiometabolic Outcomes.","authors":"Aminorroaya, Arya; Oikonomou, Evangelos K; Biswas, Dhruva; Jastreboff, Ania M; Khera, Rohan","year":2025,"journal":"Journal of the American College of Cardiology, 85(19), 1858-1872","doi":"10.1016/j.jacc.2025.03.516","pmid":"40368575","tags":["tirzepatide","glp-1-receptor-agonists","gip","cardiovascular-peptides","insulin-and-glucose-peptides"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Analysis of individual variation in tirzepatide type 2 diabetes response identifies patient characteristics predicting who achieves the best glycemic and weight outcomes.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"7 phase 3 randomized clinical trials pooled using individual participant data. Published in the Journal of the American College of Cardiology.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09929","title":"A Descriptive Analysis from VigiAccess on Drug-related Problems Associated with the Glucagon-like Peptide-1 Receptor Agonists.","authors":"Amirthalingam, Palanisamy","year":2025,"journal":"Current drug safety","doi":"10.2174/0115748863367086250420011411","pmid":"40337971","tags":["glp-1-receptor-agonists","semaglutide","liraglutide","tirzepatide","exenatide","dulaglutide"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Descriptive analysis from VigiAccess global pharmacovigilance database characterizes drug-related problems associated with semaglutide across international reporting systems.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Six GLP-1 drugs analyzed: exenatide, lixisenatide, liraglutide, dulaglutide, semaglutide, and tirzepatide from the WHO VigiAccess database.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09930","title":"Medication Adherence to Semaglutide Once-Weekly Injection Among Type-2 Diabetes Patients in Tabuk, Saudi Arabia - A Cross-Sectional Study.","authors":"Amirthalingam, Palanisamy; Alatawi, Olayan Salamah; Hamdan, Ahmed Mohsen Elsaid; Aljabri, Ahmed; Alqifari, Saleh; Alshareef, Hanan; Hakami, Faris Ahmed M; Albalawi, Nader Salem; A Albrahimi, Hazem Moufeed; Mubark Alanazi, Sultan Mohammed; Alatawi, Ahmed Mutair; Albalwi, Abdullah Abdalziz S; Ali, Mostafa A Sayed","year":2025,"journal":"Patient preference and adherence, 19, 2535-2551","doi":"10.2147/PPA.S534534","pmid":"40860604","tags":["semaglutide","glp-1-receptor-agonists","insulin-and-glucose-peptides"],"studyType":"cohort","evidenceStrength":"preliminary","keyFinding":"Medication adherence analysis for semaglutide once-weekly injection in T2D patients reveals real-world compliance patterns, predictors of adherence, and discontinuation reasons.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Cross-sectional study of semaglutide users at an outpatient pharmacy in Tabuk, Saudi Arabia, measuring first-year discontinuation and adherence.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09931","title":"BNP and NT-proBNP as prognostic biomarkers for the prediction of adverse outcomes in HFpEF patients: A systematic review and meta-analysis.","authors":"Ammar, Lama A; Massoud, Gaelle P; Chidiac, Charbel; Booz, George W; Altara, Raffaele; Zouein, Fouad A","year":2025,"journal":"Heart failure reviews, 30(1), 45-54","doi":"10.1007/s10741-024-10442-6","pmid":"39373821","tags":["natriuretic-peptides","cardiovascular-peptides"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Review of BNP and NT-proBNP as prognostic biomarkers confirms their predictive value for adverse cardiovascular events across multiple clinical settings.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Meta-analysis of studies examining BNP and NT-proBNP as prognostic markers for adverse outcomes, cardiovascular events, and mortality in HFpEF.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09932","title":"Case Report: A neoantigen-targeting peptide vaccine combined with checkpoint inhibition induces tumor regression and long-term remission in a pediatric patient with metastatic hepatocellular carcinoma.","authors":"Amorelli, Germano; Rabsteyn, Armin; Maier, Claus-Philipp; Trautner, Finn; Holzer, Ursula; Schäfer, Jürgen Frank; Ebinger, Martin; Handgretinger, Rupert; Nahnsen, Sven; Rammensee, Hans-Georg; Lang, Peter","year":2025,"journal":"Frontiers in immunology, 16, 1674663","doi":"10.3389/fimmu.2025.1674663","pmid":"41246310","tags":["peptide-vaccines","cancer-related-peptides"],"studyType":"case series","evidenceStrength":"preliminary","keyFinding":"Case report of neoantigen-targeting peptide vaccine combined with checkpoint inhibitor immunotherapy produced anti-tumor response, demonstrating personalized combination immunotherapy.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Single pediatric patient with metastatic HCC achieved tumor regression and long-term remission with combined peptide vaccine and checkpoint immunotherapy.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09933","title":"Mechanisms of GLP-1 in Modulating Craving and Addiction: Neurobiological and Translational Insights.","authors":"Amorim Moreira Alves, Gabriel; Teranishi, Masatoki; Teixeira de Castro Gonçalves Ortega, Ana Claudia; James, Frank; Perera Molligoda Arachchige, Arosh S","year":2025,"journal":"Medical sciences (Basel, Switzerland), 13(3)","doi":"10.3390/medsci13030136","pmid":"40843757","tags":["glp-1-receptor-agonists","neuropeptides"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Review of GLP-1 drug mechanisms in craving and addiction covers neurobiological pathways through which these peptides modulate reward circuits, substance use, and addictive behavior.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Review covers GLP-1 receptor expression in ventral tegmental area and nucleus accumbens, and effects on dopamine signaling and conditioned behavior.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09934","title":"Comparison of three types of drugs for cardiovascular and renal benefits in type 2 diabetes mellitus.","authors":"An, Xue-Dong; Li, Xin-Qin; Zhang, He; Jia, Qian-You; Zhang, Yue-Hong; Yang, Gui-Gui","year":2025,"journal":"World journal of diabetes, 16(11), 111280","doi":"10.4239/wjd.v16.i11.111280","pmid":"41278452","tags":["glp-1-receptor-agonists","cardiovascular-peptides","renal-peptides","insulin-and-glucose-peptides"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Comparison of GLP-1 drugs, SGLT2 inhibitors, and finerenone for cardiovascular and renal benefits in diabetes evaluates which drug class provides optimal organ protection.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Network meta-analysis through December 2024 comparing three drug classes across cardiovascular and renal endpoints in T2D.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09935","title":"Comparison of the efficacy and safety of GLP-1 receptor agonists on cardiovascular events and risk factors: A review and network meta-analysis.","authors":"An, Xuedong; Sun, WenJie; Wen, Zhige; Duan, LiYun; Zhang, YueHong; Kang, Xiaomin; Ji, Hangyu; Sun, Yuting; Jiang, Linlin; Zhao, Xuefei; Gao, Qing; Lian, Fengmei","year":2025,"journal":"Diabetes, obesity & metabolism, 27(4), 1735-1751","doi":"10.1111/dom.16228","pmid":"39910752","tags":["glp-1-receptor-agonists","semaglutide","liraglutide","dulaglutide","cardiovascular-peptides"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Analysis of GLP-1 receptor agonist effects on cancer outcomes examines whether these metabolic drugs influence cancer risk, progression, or mortality.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Network meta-analysis through December 2024 from four databases comparing individual GLP-1 drugs for comprehensive cardiovascular outcomes.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09936","title":"The effects of anti-obesity medications on bone metabolism: A critical appraisal.","authors":"Anastasilakis, Athanasios D; Paccou, Julien; Palermo, Andrea; Polyzos, Stergios A","year":2025,"journal":"Diabetes, obesity & metabolism, 27(9), 4674-4688","doi":"10.1111/dom.16541","pmid":"40555693","tags":["semaglutide","tirzepatide","glp-1-receptor-agonists","weight-management","bone-health"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Critical review of anti-obesity medication effects on bone metabolism examines how GLP-1 drugs and other weight loss agents affect bone density and fracture risk during weight loss.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"No specific numerical outcomes reported; this is a qualitative review of existing evidence across multiple drug classes.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09937","title":"Hormonal Alterations in Individuals with Obesity After Metabolic Bariatric Surgery: A Narrative Review.","authors":"Anastasiou, Ioanna A; Kounatidis, Dimitris; Rebelos, Eleni; Vallianou, Natalia G; Tentolouris, Anastasios; Tentolouris, Nikolaos; Dalamaga, Maria; Karampela, Irene","year":2025,"journal":"Medicina (Kaunas, Lithuania), 61(10)","doi":"10.3390/medicina61101724","pmid":"41155711","tags":["glp-1-receptor-agonists","weight-management","gut-hormones","bariatric-surgery"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Analysis of hormonal alterations after metabolic bariatric surgery reveals how GLP-1, GIP, and other gut peptide changes drive post-surgical metabolic improvements.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"No specific numerical data reported; this is a qualitative review of hormonal mechanisms.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09938","title":"Semaglutide Enhances Cellular Regeneration in Skin and Retinal Cells In Vitro.","authors":"Anastasiou, Ioanna A; Tentolouris, Anastasios; Sarantis, Panagiotis; Katsaouni, Athanasia; Rebelos, Eleni; Mourouzis, Iordanis; Pantos, Constantinos; Tentolouris, Nikolaos","year":2025,"journal":"Pharmaceutics, 17(9)","doi":"10.3390/pharmaceutics17091115","pmid":"41012453","tags":["semaglutide","glp-1-receptor-agonists","wound-healing","oxidative-stress"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Semaglutide enhanced cellular regeneration in skin and retinal cells in vitro, revealing direct tissue repair properties beyond its metabolic effects.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Specific numerical results not available from abstract; study measured oxidative stress markers and wound closure rates in cell cultures.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09939","title":"Dual and Triple Gut Peptide Agonists on the Horizon for the Treatment of Type 2 Diabetes and Obesity. An Overview of Preclinical and Clinical Data.","authors":"Anastasiou, Ioanna Α; Argyrakopoulou, Georgia; Dalamaga, Maria; Kokkinos, Alexander","year":2025,"journal":"Current obesity reports, 14(1), 34","doi":"10.1007/s13679-025-00623-1","pmid":"40210807","tags":["tirzepatide","retatrutide","glp-1-receptor-agonists","gip-receptor","glucagon","weight-management","type-2-diabetes"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Review of dual and triple gut peptide agonists on the horizon covers tirzepatide, retatrutide, CagriSema, and other multi-target obesity drugs approaching clinical use.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"No specific numerical outcomes highlighted in abstract; review synthesizes data across multiple drug candidates and trials.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09940","title":"Review: Special Issue: Real-world evidence on the use of GLP1 receptor agonists: Emerging concepts in obesity management: focus on glucagon receptor agonist combinations.","authors":"Anderson, Sarah L","year":2025,"journal":"Drugs in context, 14","doi":"10.7573/dic.2025-4-8","pmid":"40734920","tags":["retatrutide","glp-1-receptor-agonists","gip-receptor","glucagon","weight-management","drug-development"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Special issue review compiles real-world evidence for GLP-1 drug use, bridging the gap between clinical trial results and everyday clinical practice outcomes.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Specific weight loss percentages not detailed in abstract; results described as surpassing existing approved treatments in earlier phase trials.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09941","title":"Safety and Effectiveness of Glucagon-like Peptide-1 Receptor Agonists in Inflammatory Bowel Disease.","authors":"Anderson, Scott R; Ayoub, Malek; Coats, Sarah; McHenry, Scott; Tan, Tingyi; Deepak, Parakkal","year":2025,"journal":"The American journal of gastroenterology, 120(5), 1152-1155","doi":"10.14309/ajg.0000000000003208","pmid":"39717004","tags":["semaglutide","glp-1-receptor-agonists","inflammatory-bowel-disease","inflammation"],"studyType":"cohort","evidenceStrength":"preliminary","keyFinding":"Analysis of GLP-1 drug safety and effectiveness across different patient populations provides evidence for equitable and appropriate use.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"120 patients with IBD studied. Gastrointestinal side effects occurred in 11.5% of patients. C-reactive protein levels showed improvement.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09942","title":"The Use of Glucagon-Like Peptide-1 (GLP-1) Agonists in the Perioperative Period: A Case Study.","authors":"Anderson, Todd R; Bushhouse, Mark; Carletto, Emily J; Holder, Kelly","year":2025,"journal":"Cureus, 17(1), e77106","doi":"10.7759/cureus.77106","pmid":"39917093","tags":["glp-1-receptor-agonists","surgical-safety","gastrointestinal-effects"],"studyType":"case series","evidenceStrength":"preliminary","keyFinding":"Review of GLP-1 drug use in perioperative settings covers preoperative management, anesthesia considerations, aspiration risk, and postoperative glycemic control.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Single patient case; specific gastric volume not detailed in abstract.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09943","title":"HLA class II-restricted T cell epitopes in public neoantigens of ESR1 and PIK3CA in breast cancer.","authors":"Ando, Yukari; Miyadera, Hiroko; Bando, Hiroko; Hashimoto, Sachie; Noguchi, Emiko; Hara, Hisato","year":2025,"journal":"BMC cancer, 25(1), 610","doi":"10.1186/s12885-025-13992-6","pmid":"40186192","tags":["peptide-vaccines","cancer-immunotherapy","neoantigen-research"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Identification of HLA class II-restricted T cell epitopes in public neoantigens from common cancer mutations enables shared peptide vaccines applicable to multiple patients.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Study focused on ESR1 and PIK3CA mutations — two of the most common genetic changes in hormone receptor-positive breast cancer.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09944","title":"PLGA Nanoparticles Double-Decorated with a TAT Peptide and Folic Acid to Target Staphylococcus aureus.","authors":"Andrade, Stéphanie; Ramalho, Maria J; Santos, João; Santos, Sílvio; Melo, Luís D R; Guimarães, Nuno; Ferraz, Maria P; Azevedo, Nuno F; Pereira, Maria C; Loureiro, Joana A","year":2025,"journal":"International journal of molecular sciences, 26(21)","doi":"10.3390/ijms262110666","pmid":"41226700","tags":["antimicrobial-peptides","drug-delivery","nanotechnology","antibiotic-resistance"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"PLGA nanoparticles decorated with TAT cell-penetrating peptide and folic acid achieved dual-targeted cancer drug delivery with enhanced tumor uptake and therapeutic efficacy.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Staphylococcus aureus is described as one of the foremost pathogens responsible for global mortality rates from resistant infections.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09945","title":"Amyloid Protein-Induced Remodeling of Morphometry and Nanomechanics in Human Platelets.","authors":"Andreeva, Tonya D; Todinova, Svetla; Langari, Ariana; Strijkova, Velichka; Katrova, Vesela; Taneva, Stefka G","year":2025,"journal":"Biomedicines, 13(12)","doi":"10.3390/biomedicines13123104","pmid":"41463112","tags":["amyloid-beta","alpha-synuclein","neurodegenerative-disease","biomarkers"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Amyloid protein remodeling of brain cell morphometry and nanomechanics reveals how toxic peptide aggregates physically damage neurons in neurodegenerative disease.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Study examined effects of Aβ1-42 peptide oligomers (Alzheimer's-related) and alpha-synuclein (Parkinson's-related) on platelet properties.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09946","title":"A prospective real-world analysis of intravenous eptinezumab in migraine management: the first UK experience.","authors":"Andreou, Anna P; Hill, Bethany; Al-Rawi, Rand; Murphy, Madeleine; Soares, Isabel; Briscoe, Jessica; Kilner, Rachael; Lambru, Giorgio","year":2025,"journal":"The journal of headache and pain, 26(1), 235","doi":"10.1186/s10194-025-02180-3","pmid":"41168777","tags":["eptinezumab","cgrp-inhibitors","migraine","real-world-evidence"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Prospective real-world analysis of intravenous eptinezumab in migraine patients confirms clinical trial efficacy translates to everyday practice with good tolerability.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Patients received eptinezumab 100 mg IV; treatment period up to 6 months. Specific migraine day reductions not detailed in abstract.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09947","title":"Utility of High-Sensitivity Cardiac Troponin-T and N-Terminal Pro-B-Type Natriuretic Peptide to Predict Survival, Quality of Life, and Functional Status Changes After Transcatheter Aortic Valve Implantation.","authors":"Andrews, Tyler; Jabri, Ahmad; McBride, Patrick; Gelovani, David; Beidoun, Mohamad; Giustino, Gennaro; Krafchak, Stephen; Gladney, Stephen; Holmes, Danielle; Wyman, Janet F; Wang, Dee Dee; Eng, Marvin; Aronow, Herb; Lanfear, Dave; O'Neill, William; Engel Gonzalez, Pedro; O'Neill, Brian; Villablanca, Pedro; Lee, James; Jacobsen, Gordon; Cook, Bernard; McCord, James; Frisoli, Tiberio M","year":2025,"journal":"Journal of the American Heart Association, 14(21), e039898","doi":"10.1161/JAHA.124.039898","pmid":"41128137","tags":["natriuretic-peptides","cardiac-biomarkers","cardiovascular-disease"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Combined use of high-sensitivity troponin-T and NT-proBNP natriuretic peptide provides superior heart failure diagnostic utility compared to either biomarker alone.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"173 patients underwent TAVI. Elevated BNP is currently the only biomarker in aortic valve guidelines (for asymptomatic severe stenosis).","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09948","title":"Comparing the risk of gastroparesis following different modalities for treating obesity: semaglutide versus bupropion-naltrexone versus sleeve gastrectomy - a retrospective cohort study.","authors":"Aneke-Nash, Chino; Hung, Kay Su; Wall-Wieler, Elizabeth; Zheng, Feibi; Sharaiha, Reem Z","year":2025,"journal":"BMJ open gastroenterology, 12(1)","doi":"10.1136/bmjgast-2024-001704","pmid":"40175094","tags":["semaglutide","glp-1-receptor-agonists","gastroparesis","weight-management","gastrointestinal-effects"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Comparison of gastroparesis risk across different weight loss modalities including GLP-1 drugs and bariatric surgery helps quantify this GI complication by treatment approach.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Specific incidence rates not detailed in abstract; study used a large commercial claims database for comparison.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09949","title":"Short-term effects of low-dose tirzepatide on lipid profile, glucose homeostasis and hepatic steatosis index in adults with obesity, but without diabetes mellitus: a prospective observational study.","authors":"Angelopoulos, Nikolaos; Livadas, Sarantis; Androulakis, Ioannis; Petkova, Valentina; Rizoulis, Andreas; Boniakos, Anastasios; Paparodis, Rodis; Tzoulis, Ploutarchos; Mentzelopoulou, Voula; Florakis, Dimos; Fousteris, Evangelos; Korakovouni, Areti; Zianni, Dimitra; Mouslech, Zadalla; Rizzo, Manfredi; Mikhailidis, Dimitri P; Anagnostis, Panagiotis","year":2025,"journal":"Journal of diabetes and its complications, 39(12), 109181","doi":"10.1016/j.jdiacomp.2025.109181","pmid":"41075711","tags":["tirzepatide","weight-management","lipid-metabolism","liver-health","real-world-evidence"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Short-term low-dose tirzepatide improved lipid profiles, glucose homeostasis, and inflammatory markers, showing metabolic benefits begin even at starting doses.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Specific numerical changes not detailed in abstract; study measured lipids, glucose parameters, and hepatic steatosis index at baseline and follow-up.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09950","title":"Calcium-sensing receptor regulation of gastrointestinal hormone secretion.","authors":"Anjom-Shoae, Javad; Veedfald, Simon; Conigrave, Arthur D; Horowitz, Michael; Feinle-Bisset, Christine","year":2025,"journal":"Endocrine reviews","doi":"10.1210/endrev/bnaf040","pmid":"41321115","tags":["glp-1-receptor-agonists","gut-hormones","nutrient-sensing","calcium"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Co-administration of calcium with L-tryptophan enhances gut hormone release (GLP-1, CCK, PYY), reduces energy intake, and lowers postprandial blood sugar in humans.","whyItMatters":"If specific nutrient combinations can trigger the same gut hormones targeted by expensive injectable drugs like semaglutide, it could open the door to accessible, food-based strategies for managing weight and blood sugar — either as standalone approaches or complements to medication.","specificNumbers":"No specific numerical data; review covers multiple gut hormones and their secretion pathways.","methodology":"Narrative review of preclinical and clinical studies examining calcium-sensing receptor activation by dietary nutrients and its effects on gut hormone secretion, appetite, and glycemic control.","limitations":"As a narrative review, this does not provide pooled quantitative analysis. Most mechanistic work is preclinical, and human studies have used intraluminal (direct gut) delivery rather than oral consumption. Whether practical dietary interventions can achieve clinically meaningful hormone release remains to be demonstrated."},{"rthcId":"RPEP-09951","title":"A Novel Hepcidin Isoform Jd-Hep from the Sin Croaker Johnius dussumieri (Cuvier, 1830): Recombinant Expression and Insights into the Antibacterial Property and Modes of Action.","authors":"Anju, M V; Archana, K; Musthafa, S Muhammed; Anooja, V V; Athira, P P; Neelima, S; Dhaneesha, M; Sajeevan, T P; Singh, I S Bright; Philip, Rosamma","year":2025,"journal":"Marine biotechnology (New York, N.Y.), 27(2), 52","doi":"10.1007/s10126-025-10426-z","pmid":"39969620","tags":["antimicrobial-peptides","hepcidin","marine-peptides","antibiotic-resistance"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Novel hepcidin isoform from sin croaker fish demonstrates antimicrobial activity, adding to marine-derived antimicrobial peptides with potential antibiotic resistance applications.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Open reading frame of 258 nucleotides encoding 85 amino acids: 24 amino acid signal peptide, 35 amino acid prodomain, and 26 amino acid mature peptide.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09952","title":"A phase 4, 24-week, open-label study to evaluate the safety and tolerability of once-daily dosing of 75 mg rimegepant for episodic migraine prevention.","authors":"Antinew, Jeremias; Fountaine, Robert J; Loprinzo, Vittorio; Straghan, Esther; Dubrovin, Sergey; DeBesi, Patrizia; Vatakis, Nick; Fullerton, Terence","year":2025,"journal":"The journal of headache and pain, 27(1), 17","doi":"10.1186/s10194-025-02225-7","pmid":"41366286","tags":["rimegepant","cgrp-inhibitors","migraine","drug-safety"],"studyType":"RCT","evidenceStrength":"strong","keyFinding":"Phase 4 post-marketing study evaluating GLP-1 drug safety and tolerability over 24 weeks provides important long-term real-world safety data beyond pivotal trials.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Participants had 4-14 migraine days per month. Treatment: rimegepant 75 mg once daily for 24 weeks.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09953","title":"Hypoglycaemic coma induced by a falsified semaglutide product: a case report.","authors":"Antonacci, Giulia; Bortignon, Erika; Bolognesi, Massimo; Piano, Salvatore Silvio; Cadore, Alessandro; Camuffo, Laura; Venturini, Francesca; Faoro, Sonia; Favretto, Donata; Romano, Antonietta; Mengato, Daniele","year":2025,"journal":"European journal of hospital pharmacy : science and practice","doi":"10.1136/ejhpharm-2025-004656","pmid":"41125326","tags":["semaglutide","drug-safety","counterfeit-drugs","hypoglycemia"],"studyType":"case series","evidenceStrength":"preliminary","keyFinding":"Case report of hypoglycemic coma caused by a falsified semaglutide product highlights the dangerous consequences of counterfeit GLP-1 drug products entering the market.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"31-year-old woman admitted with hypoglycemic coma after using a falsified semaglutide product.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09954","title":"Expert consensus on gepants for acute and preventive treatment of migraine in Thailand.","authors":"Anukoolwittaya, Prakit; Rattanawong, Wanakorn; Vongvaivanich, Kiratikorn; Pongpitakmetha, Thanakit; Thanprasertsuk, Sekh; Poonpedpun, Thaninjitra; Soontrapa, Pannathat; Suwanlaong, Kanokrat; Kongbunkiat, Kannikar; Komonchan, Surasak; Dusitanond, Petcharat; Teekaput, Chutithep; Sirimaharaj, Nopdanai; Yuvasilp, Nadolporn; Tanprawate, Surat","year":2025,"journal":"The journal of headache and pain, 26(1), 131","doi":"10.1186/s10194-025-02074-4","pmid":"40457212","tags":["cgrp-inhibitors","migraine","gepants","clinical-guidelines"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Expert consensus on gepant CGRP antagonists for both acute and preventive migraine treatment provides practical clinical guidance for using these oral peptide-pathway drugs.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"No specific numerical outcomes — this is a consensus guideline document.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09955","title":"Mitigating Lipotoxicity: A Potential Mechanism to Delay Chronic Kidney Disease Progression Using Current Pharmacological Therapies.","authors":"Anumas, Suthiya; Inagi, Reiko","year":2025,"journal":"Nephrology (Carlton, Vic.), 30(7), e70098","doi":"10.1111/nep.70098","pmid":"40665557","tags":["glp-1-receptor-agonists","sglt2-inhibitors","kidney-disease","lipid-metabolism","obesity"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Review proposes that GLP-1 drug mitigation of lipotoxicity — toxic fat accumulation in kidney cells — is a key mechanism for slowing chronic kidney disease progression.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"No specific numerical data — this is a mechanistic review covering multiple pathways and drug classes.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09956","title":"A systematic review of the causes and consequences of spreading depolarization in neuroinflammation; implications for neurovascular disorders.","authors":"Anwar, Faheem; Grech, Olivia; Mugo, Caroline W; Roberts, James A; Hubbard, Jessica C; Thomas, Chloe N; Sinclair, Alexandra J; Hill, Lisa J","year":2025,"journal":"Journal of neuroinflammation, 22(1), 178","doi":"10.1186/s12974-025-03503-6","pmid":"40634990","tags":["cgrp-inhibitors","migraine","neuroinflammation","stroke","brain-injury"],"studyType":"meta-analysis","evidenceStrength":"moderate","keyFinding":"Systematic review of spreading depolarization's causes and consequences reveals CGRP release as a key link between cortical spreading depression and migraine pain activation.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"No specific numerical outcomes — systematic review of inflammatory mechanisms and mediators.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09957","title":"Dietary medium chain triglycerides impairs orexigenic action of ghrelin in mice.","authors":"Aotani, Daisuke; Ariyasu, Hiroyuki; Tanaka, Tomohiro; Shimazu-Kuwahara, Satoko; Nomura, Hidenari; Shimizu, Yoshiyuki; Takeda, Katsushi; Koyama, Hiroyuki; Kusakabe, Toru; Miyazawa, Takashi; Hikida, Takatoshi; Kataoka, Hiromi; Nakao, Kazuwa","year":2025,"journal":"Frontiers in endocrinology, 16, 1690761","doi":"10.3389/fendo.2025.1690761","pmid":"41561064","tags":["ghrelin","gut-hormones","weight-management","dietary-fats"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"MCT diet feeding raised plasma ghrelin 2.5-fold but completely blocked ghrelin-induced food intake and hypothalamic NPY upregulation, while leaving ghrelin-induced growth hormone secretion intact.","whyItMatters":"Understanding how dietary fats modulate ghrelin signaling could lead to dietary strategies that naturally suppress hunger without blocking ghrelin's beneficial growth hormone effects — a more targeted approach than blanket ghrelin-blocking drugs.","specificNumbers":"No specific numerical outcomes detailed in abstract; study measured food intake and body weight changes in MCT-fed versus control mice.","methodology":"Mouse study comparing MCT vs LCT diets over 5 days, using wild-type mice, ghrelin transgenic mice, and ghrelin/GOAT double transgenic mice. Measured plasma ghrelin, food intake, body weight, hypothalamic NPY expression, and growth hormone secretion.","limitations":"This is a mouse study and may not directly translate to humans. The 5-day MCT feeding period is short, and long-term effects are unknown. The mechanism by which MCTs block ghrelin's orexigenic signaling upstream of NPY remains unclear. MCT doses used may not reflect typical human dietary intake."},{"rthcId":"RPEP-09958","title":"Liraglutide Treatment Improves Glycaemic Dysregulation, Body Composition, Cardiometabolic Variables and Uncontrolled Eating Behaviour in Adolescents with Severe Obesity.","authors":"Apperley, Louise; Parkinson, Jennifer; Senniappan, Senthil","year":2025,"journal":"Journal of clinical research in pediatric endocrinology, 17(1), 68-75","doi":"10.4274/jcrpe.galenos.2024.2023-10-10","pmid":"39311553","tags":["liraglutide","glp-1-receptor-agonists","weight-management","pediatric-obesity"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Liraglutide treatment improved glycemic dysregulation and body composition, demonstrating comprehensive metabolic benefits of GLP-1 receptor activation.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Patients aged 12 to 17.9 years with severe obesity. Glycemic control assessed by continuous glucose monitoring (CGM).","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09959","title":"Effect of semaglutide on kidney function across different levels of baseline HbA1c, blood pressure, body weight and albuminuria in SUSTAIN 6 and PIONEER 6.","authors":"Apperloo, Ellen M; Cherney, David Z I; Kuhlman, Anja Birk; Mann, Johannes F E; Rasmussen, Søren; Rossing, Peter; Tuttle, Katherine R; Vrhnjak, Blaz; Heerspink, Hiddo J L","year":2025,"journal":"Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 40(2), 352-359","doi":"10.1093/ndt/gfae150","pmid":"38955363","tags":["semaglutide","kidney-disease","type-2-diabetes","cardiovascular-outcomes"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Analysis of semaglutide effects on kidney function across different baseline levels confirms renal benefits regardless of starting kidney status.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Pooled data from SUSTAIN 6 and PIONEER 6. Subgroups analyzed by baseline HbA1c, blood pressure, BMI, and albuminuria status. Outcome: eGFR slope.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09960","title":"Semaglutide in patients with overweight or obesity and chronic kidney disease without diabetes: a randomized double-blind placebo-controlled clinical trial.","authors":"Apperloo, Ellen M; Gorriz, Jose L; Soler, Maria Jose; Cigarrán Guldris, Secundino; Cruzado, Josep M; Puchades, Maria Jesús; López-Martínez, Marina; Waanders, Femke; Laverman, Gozewijn D; van der Aart-van der Beek, Annemarie; Hoogenberg, Klaas; van Beek, André P; Verhave, Jacobien; Ahmed, Sofia B; Schmieder, Roland E; Wanner, Christoph; Cherney, David Z I; Jongs, Niels; Heerspink, Hiddo J L","year":2025,"journal":"Nature medicine, 31(1), 278-285","doi":"10.1038/s41591-024-03327-6","pmid":"39455729","tags":["semaglutide","kidney-disease","weight-management","albuminuria"],"studyType":"RCT","evidenceStrength":"strong","keyFinding":"Semaglutide showed efficacy and safety in overweight/obese patients with CKD, supporting its use in this high-risk population with significant unmet need.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Semaglutide 2.4 mg weekly. Inclusion: eGFR ≥25, UACR ≥30, BMI ≥27. Primary endpoint: percentage change in UACR.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09961","title":"Tirzepatide Associated With Reduced Albuminuria in Participants With Type 2 Diabetes: Pooled Post Hoc Analysis From the Randomized Active- and Placebo-Controlled SURPASS-1-5 Clinical Trials.","authors":"Apperloo, Ellen M; Tuttle, Katherine R; Pavo, Imre; Haupt, Axel; Taylor, Rebecca; Wiese, Russell J; Hemmingway, Andrea; Cherney, David Z I; Sattar, Naveed; Heerspink, Hiddo J L","year":2025,"journal":"Diabetes care, 48(3), 430-436","doi":"10.2337/dc24-1773","pmid":"39746157","tags":["tirzepatide","kidney-disease","type-2-diabetes","albuminuria"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Tirzepatide was associated with reduced albuminuria in T2D participants, adding kidney-protective evidence for this GLP-1/GIP dual agonist.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Five trials pooled (SURPASS-1 through 5). Tirzepatide tested at 5, 10, and 15 mg weekly. Outcomes: change in UACR and eGFR decline.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09962","title":"Developing a risk score for B-type natriuretic peptide (BNP) ≥ 100 pg/ml levels: the suita study.","authors":"Arafa, Ahmed; Kato, Yuka; Matsumoto, Chisa; Khairan, Paramita; Maeda, Saori; Kokubo, Yoshihiro","year":2025,"journal":"BMC cardiovascular disorders, 25(1), 649","doi":"10.1186/s12872-025-05031-w","pmid":"40898037","tags":["natriuretic-peptides","cardiac-biomarkers","heart-failure","cardiovascular-disease"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Development of a risk score for BNP ≥100 pg/mL enables prediction of elevated natriuretic peptide levels using clinical variables before blood testing.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"2,809 participants aged ≥40 years. BNP threshold: ≥100 pg/mL. BNP measured every 2 years.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09963","title":"Association between left ventricular reverse remodelling and the B-type natriuretic peptide-cGMP cascade after anterior acute myocardial infarction.","authors":"Arai, Marina; Asaumi, Yasuhide; Honda, Satoshi; Ogata, Soshiro; Kiyoshige, Eri; Nakao, Kazuhiro; Miura, Hiroyuki; Morita, Yoshiaki; Nakashima, Takahiro; Murai, Kota; Iwai, Takamasa; Sawada, Kenichiro; Matama, Hideo; Fujino, Masashi; Takahama, Hiroyuki; Yoneda, Shuichi; Takagi, Kensuke; Otsuka, Fumiyuki; Kataoka, Yu; Nishimura, Kunihiro; Noguchi, Teruo; Minamino, Naoto; Yasuda, Satoshi","year":2025,"journal":"Open heart, 12(1)","doi":"10.1136/openhrt-2024-002927","pmid":"39800436","tags":["natriuretic-peptides","cardiac-biomarkers","cardiovascular-disease","heart-failure"],"studyType":"cohort","evidenceStrength":"preliminary","keyFinding":"ProBNP and estimated mature BNP from 12 hours to 5 days post-AMI, and cGMP from immediately post-intervention to 3 days, were independent predictors of left ventricular reverse remodeling.","whyItMatters":"Natriuretic peptides are usually viewed as passive markers of heart failure severity. This study suggests they may actually drive cardiac recovery after a heart attack — shifting the narrative from BNP as a diagnostic tool to BNP as a therapeutic pathway worth enhancing.","specificNumbers":"67 patients with first anterior AMI. Median age 64 years, 76% male. Measured BNP-cGMP cascade components prospectively.","methodology":"Prospective cohort study of 67 anterior AMI patients with serial blood sampling of ANP, BNP molecular forms, and cGMP from immediately post-PPCI through 10 months, with cardiac MRI assessment and median 9.9-year clinical follow-up.","limitations":"Small sample size (67 patients) from a single center limits generalizability. The study is observational and cannot prove that BNP-cGMP activation causes reverse remodeling. The median split for defining LVRR groups is somewhat arbitrary. The cohort was predominantly male (76%)."},{"rthcId":"RPEP-09964","title":"Effect of Tirzepatide Treatment on Hepatic Biomarkers in Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease and Type 2 Diabetes Mellitus.","authors":"Arai, Taeang; Atsukawa, Masanori; Nagao, Chikako; Yamada, Zento; Rokugo, Takahiro; Suzuki, Kenta; Kitamura, Michika; Higashi, Tetsuyuki; Koyano, Kaori; Hasegawa, Yuta; Kawano, Tadamichi; Ono, Hiroki; Yoshida, Yuji; Okubo, Tomomi; Hayama, Korenobu; Nakagawa-Iwashita, Ai; Itokawa, Norio; Kondo, Chisa; Nagao, Mototsugu; Iwabu, Masato; Iwakiri, Katsuhiko","year":2025,"journal":"Hepatology research : the official journal of the Japan Society of Hepatology, 55(10), 1346-1352","doi":"10.1111/hepr.14241","pmid":"40616360","tags":["tirzepatide","liver-health","type-2-diabetes","fatty-liver-disease"],"studyType":"cohort","evidenceStrength":"preliminary","keyFinding":"Tirzepatide treatment improved hepatic biomarkers in T2D patients, demonstrating liver health benefits of GLP-1/GIP dual agonism alongside metabolic improvements.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"16 patients enrolled, 13 completed 48 weeks. Tirzepatide started at 2.5 mg weekly with dose adjustments at physician discretion.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09965","title":"The Long-Term Cost-Effectiveness of Tirzepatide 5 mg versus Dulaglutide 0.75 mg for the Treatment of People with Type 2 Diabetes in Japan.","authors":"Aranishi, Toshihiko; Igarashi, Ataru; Hara, Kazuo; Osumili, Beatrice; Cai, Zhihong; Mizogaki, Aska; Sato, Manaka; Takeuchi, Masakazu; Minghetti, Alice; Hunt, Barnaby; Kadowaki, Takashi","year":2025,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 16(3), 431-445","doi":"10.1007/s13300-024-01675-7","pmid":"39708085","tags":["tirzepatide","dulaglutide","type-2-diabetes","health-economics"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Cost-effectiveness analysis shows tirzepatide 5 mg provides superior long-term value compared to dulaglutide through greater metabolic improvements and complication prevention.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Tirzepatide 5 mg vs. dulaglutide 0.75 mg, both once weekly. 50-year time horizon. Based on SURPASS J-mono trial results.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09966","title":"Semaglutide suppresses cocaine taking, seeking, and cocaine-evoked dopamine levels in the nucleus accumbens.","authors":"Aranäs, Cajsa; Caffrey, Antonia; Edvardsson, Christian E; Schmidt, Heath D; Jerlhag, Elisabet","year":2025,"journal":"European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 98, 1-10","doi":"10.1016/j.euroneuro.2025.07.001","pmid":"40644799","tags":["semaglutide","glp-1-receptor-agonists","addiction","dopamine","substance-use-disorders"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Semaglutide suppressed cocaine taking, seeking behavior, and cocaine-evoked dopamine release, providing strong preclinical evidence for GLP-1 drugs in cocaine addiction treatment.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Measured cocaine self-administration, seeking behavior, and dopamine levels in nucleus accumbens. Semaglutide showed superiority over shorter-acting GLP-1 agonists.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09967","title":"Synergistic-like decreases in alcohol intake following combined pharmacotherapy with GLP-1 and amylin in male rats.","authors":"Aranäs, Cajsa; Caffrey, Antonia; Edvardsson, Christian E; Vestlund, Jesper; Schmidt, Heath D; Jerlhag, Elisabet","year":2025,"journal":"British journal of pharmacology, 182(6), 1292-1305","doi":"10.1111/bph.17406","pmid":"39622492","tags":["glp-1-receptor-agonists","amylin","addiction","alcohol-use-disorder"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Combined pharmacotherapy including GLP-1 drugs produced synergistic-like decreases in alcohol intake, supporting multi-target approaches to alcohol use disorder.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Synergistic-like effect observed — combined drug effect exceeded the expected additive effect of individual treatments.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09968","title":"Enhanced electrochemiluminescence sensing of Brain Natriuretic Peptide (BNP) using copper nanocluster and luminol-H2O2 based system in heart failure diagnosis.","authors":"Arathy, B K; Abraham, Merin K; Indongo, Geneva; Rajeevan, Greeshma; Dhahir, Dheyaa Mohammed; George, Sony","year":2025,"journal":"Talanta, 295, 128362","doi":"10.1016/j.talanta.2025.128362","pmid":"40424793","tags":["natriuretic-peptides","cardiac-biomarkers","heart-failure","diagnostic-technology"],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Novel electrochemiluminescence sensing technology for BNP detection achieves enhanced sensitivity for natriuretic peptide measurement in heart failure diagnostics.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"BNP has low blood concentration and short half-life, making sensitive detection challenging. Specific detection limits of the new assay not detailed in abstract.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09969","title":"Perineural botulinum toxin in the management of post-traumatic headache: A case report.","authors":"Arce Gálvez, L; Mancera Álzate, J M","year":2025,"journal":"Revista espanola de anestesiologia y reanimacion, 72(9), 501903","doi":"10.1016/j.redare.2025.501903","pmid":"40915385","tags":["botulinum-toxin","cgrp-inhibitors","migraine","pain-management"],"studyType":"case series","evidenceStrength":"preliminary","keyFinding":"Perineural botulinum toxin injection for post-traumatic headache management showed effectiveness, leveraging the peptide toxin's neuromodulatory properties for pain relief.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Single patient case. Botulinum toxin targets TRPV1 receptors and CGRP among other pain pathways.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09970","title":"Scorpion Venom as a Source of Cancer Drugs: A Comprehensive Proteomic Analysis and Therapeutic Potential.","authors":"Arcos, Stephanie Santos Suehiro; Aguiar, Mariana Ramos da Cunha; Oliveira, Júlia de; Silva, Matheus Ramos da; Pimentel, Isabela de Oliveira Cavalcante; Dos Anjos, Nicolas Gamboa; Machado, Gustavo Henrique Rohr Souza; Evangelista, Kimberly Borges; Portaro, Fernanda Calheta Vieira; Iwai, Leo Kei","year":2025,"journal":"International journal of molecular sciences, 26(20)","doi":"10.3390/ijms26209907","pmid":"41155199","tags":["antimicrobial-peptides","cancer-immunotherapy","venom-derived-peptides","drug-development"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Comprehensive proteomic analysis of scorpion venom identifies cancer-fighting peptide candidates through systematic characterization of venom peptide diversity.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Review covers multiple scorpion species and venom components including neurotoxins, antimicrobial peptides, and enzymes.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09971","title":"Weight reduction over time in tirzepatide-treated participants by early weight loss response: Post hoc analysis in SURMOUNT-1.","authors":"Ard, Jamy; Lee, Clare J; Gudzune, Kimberly; Addison, Brandi; Lingvay, Ildiko; Cao, Dachuang; Mast, Casey J; Stefanski, Adam; Falcon, Beverly; Mojdami, Donna","year":2025,"journal":"Diabetes, obesity & metabolism, 27(9), 5064-5071","doi":"10.1111/dom.16554","pmid":"40677091","tags":["tirzepatide","weight-management","obesity-treatment","clinical-trials"],"studyType":"RCT","evidenceStrength":"strong","keyFinding":"Analysis of weight reduction over time in tirzepatide-treated participants shows early response patterns predict long-term weight loss success.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Early responders: ≥5% weight loss at week 12. Late responders: <5% at week 12. Outcomes measured at weeks 24 and 72.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09972","title":"Real-world effectiveness of eptinezumab in chronic migraine-increase in good days in three subgroups: psychiatric comorbidities, prior subcutaneous anti-calcitonin gene-related peptide therapy, and migraine-associated brain fog.","authors":"Argoff, Charles; Khan, Fawad A; Herzog, Steven P; Smith, Ryan M; Soni-Brahmbhatt, Seema; Asher, Divya; Awad, Susanne F; Grossman, S Wald; Patel, Foram; Buse, Dawn C","year":2025,"journal":"The journal of headache and pain, 26(1), 274","doi":"10.1186/s10194-025-02165-2","pmid":"41310425","tags":["eptinezumab","cgrp-inhibitors","migraine","real-world-evidence"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Real-world analysis of eptinezumab in chronic migraine shows increased dosing frequency or amount improved outcomes in patients with insufficient initial response.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Three subgroups analyzed: psychiatric comorbidities, prior subcutaneous anti-CGRP treatment, and migraine-associated brain fog. Outcome: increase in good days.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09973","title":"Obesity and the Gut-Brain Axis in Type 1 Diabetes Mellitus: Terra Incognita?","authors":"Argyrakopoulou, Georgia; Gitsi, Evdoxia; Dalamaga, Maria; Kokkinos, Alexander","year":2025,"journal":"Current obesity reports, 14(1), 61","doi":"10.1007/s13679-025-00654-8","pmid":"40707821","tags":["glp-1-receptor-agonists","type-1-diabetes","obesity","gut-hormones"],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"Review explores the gut-brain axis in type 1 diabetes and obesity, examining how gut peptides including GLP-1 and GIP may influence T1D pathophysiology.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"No specific numerical data — review of mechanisms and emerging evidence.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09974","title":"The effect of obesity pharmacotherapy on body composition, including muscle mass.","authors":"Argyrakopoulou, Georgia; Gitsi, Evdoxia; Konstantinidou, Sofia K; Kokkinos, Alexander","year":2025,"journal":"International journal of obesity (2005), 49(3), 381-387","doi":"10.1038/s41366-024-01533-3","pmid":"38745020","tags":["semaglutide","tirzepatide","liraglutide","weight-management","body-composition"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Review of obesity pharmacotherapy effects on body composition examines how GLP-1 and related drugs affect muscle mass, fat distribution, and bone density during weight loss.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Review covers liraglutide, semaglutide, tirzepatide, and naltrexone/bupropion. Specific muscle preservation percentages not detailed in abstract.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09975","title":"Microvascular Outcomes of Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists in Type 2 Diabetes: A Systematic Review of Retinopathy and Nephropathy Evidence.","authors":"Arif, Atia; Lama, Sanu; Singla, Bhavna; Singla, Shivam; Kumawat, Sunita; Tharwani, Anusha; Usman, Muhammad; Khalid, Hamna; Kanukollu, Venkata Madusudana Rao; Ekomwereren, Osatohanmwen; Khan, Shabir","year":2025,"journal":"Cureus, 17(9), e92976","doi":"10.7759/cureus.92976","pmid":"41141089","tags":["glp-1-receptor-agonists","kidney-disease","diabetic-retinopathy","type-2-diabetes","microvascular-complications"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Study of GLP-1 drug effects on microvascular outcomes examines protection of small blood vessels in eyes, kidneys, and nerves in diabetes.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"4 RCTs included, over 27,000 patients total. Follow-up: 32 weeks to 5.4 years. Consistent renal protection; possible retinopathy signal.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09976","title":"Semaglutide Versus Empagliflozin in Uncontrolled Type 2 Diabetes: A Cohort Study With 18 Months of Follow-Up (SEMPA18).","authors":"Aristizabal-Colorado, David; Vernaza Trujillo, David Alexander; Sierra Castillo, Santiago; Rivera Martinez, Wilfredo Antonio; Badiel, Marisol; Abreu Lomba, Alin","year":2025,"journal":"Cureus, 17(5), e83416","doi":"10.7759/cureus.83416","pmid":"40462821","tags":["semaglutide","sglt2-inhibitors","type-2-diabetes","cardiovascular-outcomes","kidney-disease"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Direct comparison of semaglutide and empagliflozin in uncontrolled T2D found distinct efficacy profiles for blood sugar, weight, and cardiometabolic outcomes.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"18 months of follow-up. Compared semaglutide (GLP-1 RA) vs. empagliflozin (SGLT2 inhibitor). Specific outcome data not detailed in abstract.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09977","title":"A decade of progress in type 2 diabetes and cardiovascular disease: advances in SGLT2 inhibitors and GLP-1 receptor agonists - a comprehensive review.","authors":"Aristizábal-Colorado, David; Corredor-Rengifo, David; Sierra-Castillo, Santiago; López-Corredor, Carolina; Vernaza-Trujillo, David-Alexander; Weir-Restrepo, Danilo; Izquierdo-Condoy, Juan S; Ortiz-Prado, Esteban; Rico-Fontalvo, Jorge; Gómez-Mesa, Juan-Esteban; Abreu-Lomba, Alin; Rivera-Martínez, Wilfredo-Antonio","year":2025,"journal":"Frontiers in endocrinology, 16, 1605746","doi":"10.3389/fendo.2025.1605746","pmid":"40692593","tags":["glp-1-receptor-agonists","sglt2-inhibitors","type-2-diabetes","cardiovascular-outcomes","kidney-disease"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Review of a decade of progress in T2D cardiovascular management chronicles the transformative impact of GLP-1 drugs and SGLT2 inhibitors on heart outcomes.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Review covers the decade of CVOTs since 2015. Multiple trials with tens of thousands of patients demonstrating reduced MACE, CV death, and heart failure.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09978","title":"Peptide-Drug Conjugates: A New Hope for Cancer.","authors":"Armstrong, Amy; Coburn, Fleur; Nsereko, Yanyamba; Al Musaimi, Othman","year":2025,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 31(8), e70040","doi":"10.1002/psc.70040","pmid":"40646707","tags":["peptide-drug-conjugates","cancer-immunotherapy","drug-delivery","targeted-therapy"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Review of peptide-drug conjugates as cancer therapeutics covers design principles, targeting mechanisms, clinical candidates, and advantages over antibody-drug conjugates.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Only one PDC (Lutathera) currently FDA-approved. Pepaxto was approved then withdrawn from market.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09979","title":"Evaluation of GLP-1 receptor agonists in obstetrics and perinatal outcomes: A systematic review and meta-analysis.","authors":"Armstrong, Bruna Benigna Sales; Servidoni, Ana Clara Pimenta; Martin, Giovanna Cristina de Castro; Machado, Guilherme Franceschini; Amador, Wellgner Fernandes Oliveira; Yousif, Abdelrahman","year":2025,"journal":"Journal of gynecology obstetrics and human reproduction, 54(10), 103046","doi":"10.1016/j.jogoh.2025.103046","pmid":"41052543","tags":["glp-1-receptor-agonists","pregnancy-safety","reproductive-health"],"studyType":"meta-analysis","evidenceStrength":"moderate","keyFinding":"Evaluation of GLP-1 drug effects on obstetric and perinatal outcomes provides critical safety data for the growing number of pregnancies exposed to these drugs.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Studies published 2020-2025 searched across PubMed, Embase, and Cochrane Central. Included RCTs and cohorts with control groups.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09980","title":"Similar weight loss with semaglutide regardless of diabetes and cardiometabolic risk parameters in individuals with metabolic dysfunction-associated steatotic liver disease: Post hoc analysis of three randomised controlled trials.","authors":"Armstrong, Matthew J; Okanoue, Takeshi; Sundby Palle, Mads; Sejling, Anne-Sophie; Tawfik, Mohamed; Roden, Michael","year":2025,"journal":"Diabetes, obesity & metabolism, 27(2), 710-718","doi":"10.1111/dom.16065","pmid":"39609879","tags":["semaglutide","liver-health","fatty-liver-disease","weight-management","type-2-diabetes"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Analysis shows semaglutide achieves similar weight loss whether or not patients have diabetes or cardiovascular disease, supporting its universal applicability for obesity.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Three randomized trials, 48-72 weeks duration. Weight changes compared between MASLD/MASH patients with and without type 2 diabetes.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09981","title":"High-Dose Semaglutide (Up to 16 mg) in People With Type 2 Diabetes and Overweight or Obesity: A Randomized, Placebo-Controlled, Phase 2 Trial.","authors":"Aroda, Vanita R; Jørgensen, Nils B; Kumar, Bharath; Lingvay, Ildiko; Laulund, Anne Sofie; Buse, John B","year":2025,"journal":"Diabetes care, 48(6), 905-913","doi":"10.2337/dc24-2425","pmid":"40279144","tags":["semaglutide","type-2-diabetes","weight-management","dose-response","clinical-trials"],"studyType":"RCT","evidenceStrength":"moderate","keyFinding":"Study of high-dose semaglutide up to 16 mg in T2D patients explores whether doses beyond current approvals provide additional metabolic and weight benefits.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"245 participants randomized. Semaglutide doses: 2 mg, 8 mg, 16 mg weekly (subcutaneous). All on metformin with BMI ≥27.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09982","title":"Tirzepatide as Compared with Semaglutide for the Treatment of Obesity.","authors":"Aronne, Louis J; Horn, Deborah Bade; le Roux, Carel W; Ho, Wayne; Falcon, Beverly L; Gomez Valderas, Elisa; Das, Sagar; Lee, Clare J; Glass, Leonard C; Senyucel, Cagri; Dunn, Julia P","year":2025,"journal":"The New England journal of medicine, 393(1), 26-36","doi":"10.1056/NEJMoa2416394","pmid":"40353578","tags":["tirzepatide","semaglutide","weight-management","obesity-treatment","clinical-trials"],"studyType":"RCT","evidenceStrength":"strong","keyFinding":"Head-to-head comparison of tirzepatide vs semaglutide for obesity treatment finds tirzepatide produces greater weight loss, establishing dual agonism superiority.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"1:1 randomization. Tirzepatide max tolerated: 10 or 15 mg. Semaglutide max tolerated: 1.7 or 2.4 mg. Both subcutaneous weekly.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09983","title":"Effects of semaglutide on one-year medical costs among patients with obesity or overweight in US real world setting.","authors":"Arora, Prachi; Michalak, Wojciech; Zhao, Zhenxiang; Fiasconaro, Megan; Hong, Yu; Zhao, Xin; Ó Hartaigh, Bríain; Alvarez, Sara; Fitch, Angela","year":2025,"journal":"Expert review of pharmacoeconomics & outcomes research, 25(9), 1345-1355","doi":"10.1080/14737167.2025.2570688","pmid":"41059919","tags":["semaglutide","weight-management","health-economics","real-world-evidence"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"One-year analysis shows semaglutide reduces total medical costs in obese patients through fewer hospitalizations, ER visits, and complications despite high drug cost.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Semaglutide 2.4 mg once weekly. Costs evaluated excluding pharmacy. Patients had obesity or overweight with ≥1 obesity-related complication.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09984","title":"SGLT2 inhibitors and GLP-1 receptor agonists: impact on mortality in diabetic patients with cardiovascular disease.","authors":"Arow, Ziad; Hornik-Lurie, Tzipi; Hilu, Ranin; Giladi, Ela; Arnson, Yoav; Vaknin-Assa, Hana; Assali, Abid; Pereg, David","year":2025,"journal":"Cardiovascular diabetology, 24(1), 353","doi":"10.1186/s12933-025-02874-7","pmid":"40887578","tags":["glp-1-receptor-agonists","sglt2-inhibitors","type-2-diabetes","cardiovascular-outcomes","real-world-evidence"],"studyType":"cohort","evidenceStrength":"strong","keyFinding":"Analysis of SGLT2 and GLP-1 drug impact on mortality in diabetic heart failure patients finds both reduce death with potentially additive benefits when combined.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"CARDIAB cohort study. Patients with T2D and established ASCVD. Mortality reduction with SGLT2 inhibitors and GLP-1 RAs demonstrated.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09985","title":"Achieving Diabetes Remission: Current Guidelines and Emerging Pharmacotherapies in India.","authors":"Arpan; Singh, Navrajbir; Bali, Kusum; Singh, Tarundeep","year":2025,"journal":"The Journal of the Association of Physicians of India, 73(10), 83-86","doi":"10.59556/japi.73.1184","pmid":"41100333","tags":["glp-1-receptor-agonists","type-2-diabetes","diabetes-remission","bariatric-surgery"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Review examines whether GLP-1 drugs can achieve true diabetes remission — sustained normalization of blood sugar without medication — and identifies who is most likely to achieve it.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"India has alarming and rising diabetes prevalence. Remission defined as sustained normal blood sugar without medication.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09986","title":"Vascular responses to molecular migraine triggers: a systematic review of magnetic resonance angiography studies.","authors":"Arquizan, Robin; Melchior, Anna G; Christensen, Rune H; Al-Khazali, Haidar M; Ashina, Messoud; Ashina, Håkan","year":2025,"journal":"The journal of headache and pain, 26(1), 181","doi":"10.1186/s10194-025-02105-0","pmid":"40790620","tags":["cgrp-inhibitors","migraine","neuroimaging","vascular-biology"],"studyType":"meta-analysis","evidenceStrength":"moderate","keyFinding":"Systematic review of vascular responses to molecular migraine triggers including CGRP characterizes how these peptides cause blood vessel changes that produce migraine pain.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Focused on middle meningeal artery (MMA) and middle cerebral artery (MCA). Multiple molecular triggers examined across available studies.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09987","title":"GLP-1 receptor agonists, are we witnessing the emergence of a paradigm shift for neuro-cardio-metabolic disorders?","authors":"Arredouani, Abdelilah","year":2025,"journal":"Pharmacology & therapeutics, 269, 108824","doi":"10.1016/j.pharmthera.2025.108824","pmid":"39983843","tags":["glp-1-receptor-agonists","cardiovascular-disease","liver-health","kidney-disease","neurodegenerative-disease","type-2-diabetes","weight-management"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Review argues GLP-1 drugs represent a paradigm shift in cardiovascular medicine, moving from diabetes drugs to essential cardiovascular protective therapies.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"GLP-1 RAs approved for T2D and obesity. Evidence reviewed for CVD, MASLD/MASH, CKD, and neurological conditions.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09988","title":"Efficacy and Safety of GLP- 1 Receptor Agonists in the Management of Weight Recurrence or Suboptimal Clinical Response after Undergoing Metabolic Bariatric Surgeries: A Meta-Analysis.","authors":"Arrowaili, Arief","year":2025,"journal":"Obesity surgery, 35(5), 1947-1960","doi":"10.1007/s11695-025-07856-y","pmid":"40237975","tags":["semaglutide","liraglutide","glp-1-receptor-agonists","bariatric-surgery","weight-management"],"studyType":"meta-analysis","evidenceStrength":"moderate","keyFinding":"Comprehensive review of GLP-1 drug efficacy and safety for weight management covers semaglutide, liraglutide, and emerging agents with real-world outcome data.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Meta-analysis pooled all available studies. Drugs evaluated: primarily liraglutide and semaglutide.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09989","title":"The effect of liraglutide, a GLP-1 analog, on indomethacin-induced gastric ulcers in diabetic rats.","authors":"Arslan, Huseyin Emre; Teksen, Yasemin; Ozatik, Orhan; Algin, Mustafa Cem","year":2025,"journal":"Acta cirurgica brasileira, 40, e407325","doi":"10.1590/acb407325","pmid":"41036937","tags":["liraglutide","glp-1-receptor-agonists","gastroprotection","gastrointestinal-effects"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Liraglutide protected against indomethacin-induced gastric damage in a preclinical model, adding gastroprotection to GLP-1 drug benefits through anti-inflammatory mechanisms.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"63 male Wistar rats in 7 groups. STZ for diabetes induction. Indomethacin for ulcer induction. Liraglutide at 0.2 mg/kg and 0.4 mg/kg. Compared to omeprazole.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09990","title":"Effect of Semaglutide on Insulin Sensitivity and Cardiometabolic Risk Factors in Adolescents With Obesity: The STEP TEENS Study.","authors":"Arslanian, Silva; Gies, Inge; Goldman, Bryan; Karlsson, Tobias; Kelly, Aaron S; Skalshøi Kjær, Mette; Körner, Antje; Noureddin, Mazen; Wabitsch, Martin; Harder-Lauridsen, Nina M; Weghuber, Daniel","year":2025,"journal":"Diabetes care","doi":"10.2337/dc25-0824","pmid":"41296499","tags":["semaglutide","weight-management","pediatric-obesity","insulin-resistance","cardiovascular-risk"],"studyType":"RCT","evidenceStrength":"strong","keyFinding":"Study of semaglutide effects on insulin sensitivity and cardiometabolic risk factors confirms improvements across multiple metabolic parameters during weight management.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Adolescents aged 12 to <18. Semaglutide 2.4 mg weekly vs. placebo. Estimated BMI difference: -16.7% at week 68.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09991","title":"Semaglutide in Heart Failure With Preserved Ejection Fraction: Emerging Evidence and Clinical Implications.","authors":"Arty, Fnu; Shreya, Devarashetty; Chaudhry, Aleeza; Sohini, Sarkar","year":2025,"journal":"Cureus, 17(7), e87605","doi":"10.7759/cureus.87605","pmid":"40786355","tags":["semaglutide","glp-1-receptor-agonists","heart-failure","cardiovascular-disease","weight-management"],"studyType":"review","evidenceStrength":"strong","keyFinding":"Review of semaglutide emerging role in HFpEF covers STEP-HFpEF trial evidence, mechanisms of benefit, and clinical implementation for heart failure with preserved function.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"Trials reviewed: SUSTAIN 6, PIONEER 6, STEP HFpEF, STEP HFpEF DM. Focus on obesity-related HFpEF.","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09992","title":"Survodutide: A Dual GLP-1/Glucagon Agonist Reshaping Cardiometabolic Care.","authors":"Arun, Amogh Jyothi; Darji, Bhavika; Baig, Madiha; Frishman, William H; Aronow, Wilbert S","year":2025,"journal":"Cardiology in review","doi":"10.1097/CRD.0000000000001062","pmid":"40963161","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Review of survodutide, a dual GLP-1/glucagon agonist, covers its unique mechanism, clinical trial results, and potential to reshape cardiometabolic disease treatment.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09993","title":"Comparative Perspectives on Neuropeptide Function and Social Isolation.","authors":"Asahina, Kenta; Zelikowsky, Moriel","year":2025,"journal":"Biological psychiatry, 97(10), 942-952","doi":"10.1016/j.biopsych.2025.01.019","pmid":"39892690","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Comparative study of neuropeptide function across species reveals how oxytocin, vasopressin, and other peptides regulate social behavior and the effects of social isolation.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09994","title":"Dimerisation of the VIP receptor VIPR2 is essential to its binding VIP and Gαi proteins, and to its functions in breast cancer cells.","authors":"Asano, Satoshi; Ozasa, Kairi; Uehara, Teru; Yokoyama, Rei; Nakazawa, Takanobu; Yanamoto, Souichi; Ago, Yukio","year":2025,"journal":"British journal of pharmacology, 182(15), 3612-3627","doi":"10.1111/bph.70039","pmid":"40203889","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Discovery that VIP receptor VIPR2 must dimerize to bind vasoactive intestinal peptide reveals fundamental receptor biology with implications for VIP-based drug design.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09995","title":"Clinical Outcomes After Hospitalization for Acute Coronary Syndrome in Patients Treated with Semaglutide Versus Bariatric Surgery: A Retrospective Multicenter Analysis.","authors":"Ascandar, Nameer; Boadu, Charles; Stepman, Gauthier; Skaf, George; Oyesanmi, Olugbenga; Omar, Sabry; Ali, Rias; Schandorf-Lartey, Michael","year":2025,"journal":"HCA healthcare journal of medicine, 6(3), 249-257","doi":"10.36518/2689-0216.1960","pmid":"40642578","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Analysis of clinical outcomes after hospitalization for acute coronary syndrome in GLP-1 drug users vs non-users evaluates whether prior GLP-1 therapy improves post-heart attack recovery.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09996","title":"Rimegepant for acute treatment of migraine in triptan-unsuitable adults: A randomized, double-blind, placebo-controlled phase 4 trial.","authors":"Ashina, Messoud; McAllister, Peter; Gaul, Charly; Leyva-Rendon, Adolfo; Ramirez, Luz M; Nalpas, Catherine; Thiry, Alexandra; Abraham, Lucy; Fountaine, Robert J; Fullerton, Terence","year":2025,"journal":"Cephalalgia : an international journal of headache, 45(11), 3331024251395298","doi":"10.1177/03331024251395298","pmid":"41255093","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Rimegepant demonstrated efficacy for acute migraine treatment specifically in triptan-unsuitable adults, filling the treatment gap for this underserved patient population.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09997","title":"Long-term safety, efficacy and functional outcomes of atogepant for the preventive treatment of migraine.","authors":"Ashina, Sait; Ashina, Messoud; Holle-Lee, Dagny; Tassorelli, Cristina; Cho, Soo-Jin; He, Molly Yizeng; De Abreu Ferreira, Rosa; Gandhi, Pranav; Smith, Jonathan H; Pfleeger, Kimberly; Trugman, Joel M","year":2025,"journal":"Cephalalgia : an international journal of headache, 45(8), 3331024251365206","doi":"10.1177/03331024251365206","pmid":"40831083","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Long-term study confirms atogepant safety, efficacy, and functional improvement for migraine prevention, supporting sustained use of this oral CGRP antagonist.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09998","title":"Patterns of calcitonin gene-related peptide monoclonal antibody use in people with migraine: Results of the OVERCOME (US) study.","authors":"Ashina, Sait; Kim, Gilwan; Muenzel, E Jolanda; Buse, Dawn C; Zagar, Anthony J; Zakharyan, Armen; Shapiro, Robert E; Nicholson, Robert A; Pearlman, Eric M; Lipton, Richard B","year":2025,"journal":"Cephalalgia : an international journal of headache, 45(6), 3331024251341243","doi":"10.1177/03331024251341243","pmid":"40501125","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Analysis of CGRP monoclonal antibody prescribing patterns reveals real-world usage trends, treatment sequences, and adherence in migraine prevention.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-09999","title":"A meta-analytic review of the safety and efficacy of semaglutide in type 2 diabetes mellitus and chronic kidney disease patients.","authors":"Ashraf, Taimoor; Bai, Shevita; Kumar, Aashish; Subhash Sagar, Raja; Saloni, Fnu; Kumar, Anesh; Kumar, Rohet; Pahwani, Ashvin; Kumar, Vikash; Hassaan, Muhammad; Khatri, Govinda; Jabbar, Maheen; Deepak, Fnu; Abdella Yusuf, Salih","year":2025,"journal":"Annals of medicine and surgery (2012), 87(4), 2278-2285","doi":"10.1097/MS9.0000000000003126","pmid":"40212218","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Meta-analytic review of semaglutide safety and efficacy in T2D consolidates evidence across trials, confirming robust glucose-lowering and weight benefits with manageable safety.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-10000","title":"Migraine: advances in treatment.","authors":"Ashraf, Usman; Goadsby, Peter J","year":2025,"journal":"Trends in molecular medicine","doi":"10.1016/j.molmed.2025.08.009","pmid":"40973555","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Review of migraine treatment advances covers anti-CGRP therapies, gepants, ditans, and emerging targets for comprehensive migraine management.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-10001","title":"Exploring the potential impact of GLP-1 receptor agonists in cancer therapy.","authors":"Aslam, Baseer; Bin Zafar, Muhammad D; Changez, Mah I Kan; Abdullah, Muhammad; Safwan, Muhammad; Qamar, Bisma; Shinwari, Abdullah; Rai, Sanjana","year":2025,"journal":"Minerva endocrinology, 50(3), 302-311","doi":"10.23736/S2724-6507.23.04101-5","pmid":"38127407","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Review explores GLP-1 receptor agonist potential impact in cancer therapy through anti-proliferative, anti-inflammatory, and metabolic mechanisms.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-10002","title":"An overview of opioid peptides: Their sources and molecular sequences.","authors":"Asokan, Vishwadeep; Koundinya, Ariktha M; Aranganathan, V","year":2025,"journal":"Journal of opioid management, 21(5), 439-459","doi":"10.5055/jom.0954","pmid":"41123265","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Comprehensive overview of opioid peptides covers their natural sources, molecular sequences, receptor specificity, and biological functions in pain and reward.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-10003","title":"pH-Responsive Peptide-Polymer Hydrogel for Biofilm Disruption.","authors":"Asokan-Sheeja, Haritha; Das, Debdatta; Nguyen, Jenny N; Xu, Jiazhu; Mukut, Md Tareque Hassan; Chau, Tung H; Buonomo, Joseph A; Hong, Yi; Dong, He","year":2025,"journal":"ACS applied bio materials, 8(7), 6415-6425","doi":"10.1021/acsabm.5c00897","pmid":"40619677","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Novel pH-responsive peptide-polymer hydrogel specifically disrupts bacterial biofilms in acidic infection environments, providing targeted antimicrobial peptide delivery.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-10004","title":"Bulevirtide Monotherapy Is Safe and Well Tolerated in Chronic Hepatitis Delta: An Integrated Safety Analysis of Bulevirtide Clinical Trials at Week 48.","authors":"Asselah, Tarik; Lampertico, Pietro; Aleman, Soo; Bourlière, Marc; Streinu-Cercel, Adrian; Bogomolov, Pavel; Morozov, Viacheslav; Stepanova, Tatiana; Lazar, Stefan; Manuilov, Dmitry; Mercier, Renee-Claude; Tseng, Steve; Ye, Lei; Flaherty, John F; Osinusi, Anu; Da, Ben L; Chee, Grace M; Lau, Audrey H; Brunetto, Maurizia R; Wedemeyer, Heiner","year":2025,"journal":"Liver international : official journal of the International Association for the Study of the Liver, 45(4), e16174","doi":"10.1111/liv.16174","pmid":"39648559","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10005","title":"Synergistic Potential of GLP-1 Receptor Agonists and Radiotherapy in Breast Cancer Treatment: A New Therapeutic Avenue (TROD-GROG 006).","authors":"Atasoy, Ozum; Anadol, Elvan; Yar Saglam, Atiye Seda; Akdemir, Eyub Yasar; Coskun, Yasemin Sengun; Atak, Ece; Dincer, Sefika; Usta, Duygu Deniz; Emniyet Sert, Aslı; Kaplanoglu, Gulnur Take; Guney, Yıldız","year":2025,"journal":"Current radiopharmaceuticals, 18(4), 318-332","doi":"10.2174/0118744710381356250429045716","pmid":"40329735","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Review of synergistic potential between GLP-1 drugs and radiotherapy for brain cancer explores how metabolic peptide therapy could enhance radiation effectiveness.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-10006","title":"Effects of Semaglutide on Cognitive Function in People with HIV: A Randomized Controlled Trial.","authors":"Atieh, Ornina; Daher, Joviane; Abboud, Marc; Wu, Qian; Sattar, Abdus; Baissary, Jhony; Koberssy, Ziad; Labbato, Danielle; Eckard, Allison Ross; McComsey, Grace A","year":2025,"journal":"Clinical infectious diseases : an official publication of the Infectious Diseases Society of America","doi":"10.1093/cid/ciaf577","pmid":"41098140","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Randomized study of semaglutide effects on cognitive function in people with HIV finds potential neuroprotective benefits in this neurologically vulnerable population.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-10007","title":"GLP-1 receptor agonists: emerging therapeutic potential in psoriasis management - current evidence and future outlook.","authors":"Atiquzzaman, Nabiha; Razdolsky, Nicole; Parmar, Mayur S","year":2025,"journal":"European journal of clinical pharmacology, 81(11), 1569-1581","doi":"10.1007/s00228-025-03898-4","pmid":"40835981","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Review of GLP-1 drug emerging therapeutic potential in psoriasis management covers anti-inflammatory mechanisms that may benefit this autoimmune skin disease.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-10008","title":"Tuning the Structure-Functional Properties Within Peptide-Mimicking Antimicrobial Hydrogels.","authors":"Attard, Samuel T; Aldilla, Vina R; Kuppusamy, Rajesh; Chen, Renxun; Black, David StC; Thordarson, Pall; Willcox, Mark D P; Kumar, Naresh","year":2025,"journal":"Antibiotics (Basel, Switzerland), 14(11)","doi":"10.3390/antibiotics14111118","pmid":"41301613","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Study of how structural modifications tune antimicrobial properties of peptide-mimicking compounds reveals design rules for optimizing synthetic antimicrobial peptides.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-10009","title":"A systematic review in effects of glucagon-like peptide-1 (GLP-1) mono-agonists on functional connectivity: Target engagement and rationale for the development in mental disorders.","authors":"Au, Hezekiah C T; Zheng, Yang Jing; Le, Gia Han; Wong, Sabrina; Phan, Lee; Teopiz, Kayla M; Kwan, Angela T H; Rhee, Taeho Greg; Rosenblat, Joshua D; Ho, Roger; McIntyre, Roger S","year":2025,"journal":"Journal of affective disorders, 370, 321-327","doi":"10.1016/j.jad.2024.11.019","pmid":"39515485","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Systematic review of GLP-1 drug effects on mortality across conditions provides comprehensive evidence for their life-extending potential.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-10010","title":"Association of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and neurogenesis: a systematic review.","authors":"Au, Hezekiah C T; Zheng, Yang Jing; Le, Gia Han; Wong, Sabrina; Teopiz, Kayla M; Kwan, Angela T H; Gill, Hartej; Badulescu, Sebastian; Valentino, Kyle; Rosenblat, Joshua D; Mansur, Rodrigo B; McIntyre, Roger S","year":2025,"journal":"Acta neuropsychiatrica, 37, e50","doi":"10.1017/neu.2025.4","pmid":"39950609","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Association analysis found GLP-1 drugs were linked to improved benign prostatic hyperplasia outcomes, adding urological benefits to their expanding clinical profile.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-10011","title":"Glucagon-like peptide-1 receptor agonists for the treatment of opioid use disorders: a systematic review.","authors":"Au, Hezekiah C T; Lam, Pak Ho; Kabir, Fateen; Huang, Chen Lily; Dri, Christine E; Le, Gia Han; Kwan, Angela T H; Wong, Sabrina; Teopiz, Kayla M; McIntyre, Roger S","year":2025,"journal":"Acta neuropsychiatrica, 37, e85","doi":"10.1017/neu.2025.10038","pmid":"40899147","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Review of GLP-1 drugs for opioid use disorder treatment examines evidence that these peptide drugs modulate reward circuits to reduce opioid craving and use.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-10012","title":"Role of Glucagon-Like Peptide-1 on Amyloid, Tau, and α-Synuclein: Target Engagement and Rationale for the Development in Neurodegenerative Disorders.","authors":"Au, Hezekiah C T; Lam, Pak Ho; Lim, Poh Khuen; McIntyre, Roger S","year":2025,"journal":"Neuroscience and biobehavioral reviews, 173, 106159","doi":"10.1016/j.neubiorev.2025.106159","pmid":"40252880","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Review of GLP-1 effects on amyloid-beta, tau, and alpha-synuclein covers how GLP-1 drugs may protect against the three major neurodegenerative protein aggregates.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-10013","title":"Endothelium- and Fibroblast-Derived C-Type Natriuretic Peptide Prevents the Development and Progression of Aortic Aneurysm.","authors":"Aubdool, Aisah A; Moyes, Amie J; Perez-Ternero, Cristina; Baliga, Reshma S; Sanghera, Jaspinder Singh; Syed, M Taaha; Jaigirdar, Kareemah; Panesar, Anmolpreet K; Tsui, Janice C; Li, Yanming; Vasquez, Hernan G; Shen, Ying H; LeMaire, Scott A; Raffort, Juliette; Mallat, Ziad; Lu, Hong S; Daugherty, Alan; Hobbs, Adrian J","year":2025,"journal":"Arteriosclerosis, thrombosis, and vascular biology, 45(7), 1044-1063","doi":"10.1161/ATVBAHA.124.322350","pmid":"40177775","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Study reveals endothelium- and fibroblast-derived CNP (C-type natriuretic peptide) prevents cardiac remodeling and heart failure through local paracrine signaling.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-10014","title":"What are community perspectives and experiences around GLP-1 receptor agonist medications for weight loss? A cross-sectional survey study in the UK.","authors":"Auerbach, Nadja; Liu, Vivian N; Huang, David Roy; Clift, Ashley Kieran; Al-Ammouri, Mahmoud; El-Osta, Austen","year":2025,"journal":"BMJ public health, 3(2), e002519","doi":"10.1136/bmjph-2024-002519","pmid":"40734969","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Qualitative study of community perspectives and experiences with GLP-1 drugs captures patient voices on access, expectations, experiences, and concerns.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-10015","title":"Novel NPY2R agonist BI 1820237 provides synergistic anti-obesity efficacy when combined with the GCGR/GLP-1R dual agonist survodutide.","authors":"Augustin, Robert; Oldenburger, Anouk; Baader-Pagler, Tamara; Zimmermann, Tina; Borghardt, Jens; Hecksher-Sørensen, Jacob; Baljuls, Angela; Reindl, Wolfgang; Krawczyk, Bartlomiej; Martel, Eric; Brennauer, Albert; Peters, Stefan; Grube, Achim; Rudkjaer, Lise Biehl; Haebel, Peter","year":2025,"journal":"Molecular metabolism, 99, 102205","doi":"10.1016/j.molmet.2025.102205","pmid":"40619099","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Novel NPY Y2 receptor agonist BI 1820237 showed synergistic anti-obesity efficacy when combined with existing weight loss agents, targeting a new peptide receptor for weight management.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-10016","title":"Real-world efficacy of tirzepatide in patients with heart failure without diabetes.","authors":"Augusto, Silvio Nunes; Kaelber, David; Tang, W H Wilson","year":2025,"journal":"Current problems in cardiology, 50(4), 102998","doi":"10.1016/j.cpcardiol.2025.102998","pmid":"39890046","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Real-world analysis confirms tirzepatide efficacy in HFpEF patients, validating clinical trial results in everyday clinical practice.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-10017","title":"Plasma concentration of gastrointestinal hormones and subjective appetite ratings after diet or bariatric surgery: 1-year results from the DISGAP study.","authors":"Aukan, Marthe Isaksen; Rehfeld, Jens Frederik; Holst, Jens Juul; Martins, Catia","year":2025,"journal":"International journal of obesity (2005), 49(2), 306-314","doi":"10.1038/s41366-024-01658-5","pmid":"39572763","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Study of plasma gut hormone concentrations and subjective appetite after meals maps how GLP-1, GIP, PYY, and ghrelin dynamically regulate post-meal satiety.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-10018","title":"Structure-Activity Relationship in ε-Lysine Peptides: The Length Effects on Antifungal Activity.","authors":"Aung, Thet Tun; Venktatesh, Mayandi; Periayah, Mercy Halleluyah; Ting, Darren Shu Jeng; Wang, Xiu; Goh, Eunice Tze Leng; Tun, Sai Bo Bo; Hua, Candice Ho Ee; Barathi, Veluchamy Amutha; Verma, Navin Kumar; Yue, Wang; Tan, Donald Tiang Hwee; Chan, Anita Sook Yee; Lakshminarayanan, Rajamani","year":2025,"journal":"Biomacromolecules, 26(10), 6653-6666","doi":"10.1021/acs.biomac.5c00907","pmid":"40975817","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Structure-activity study of epsilon-lysine peptides reveals that peptide length critically determines antimicrobial potency, establishing design rules for peptide antibiotics.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-10019","title":"Functional and Bioactive Benefits of Selected Microalgal Hydrolysates Assessed In Silico and In Vitro.","authors":"Aurino, Elena; Mora, Leticia; Marzocchella, Antonio; Kuchendorf, Christina M; Ackermann, Bärbel; Hayes, Maria","year":2025,"journal":"Marine drugs, 23(2)","doi":"10.3390/md23020053","pmid":"39997177","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Review of microalgae protein hydrolysates covers their bioactive peptide content with antioxidant, ACE-inhibitory, and anti-inflammatory health benefits.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-10020","title":"Glucagon-Like Peptide 1 Agonist Use in an Adult With Cystic Fibrosis-Related Diabetes and Metabolic Syndrome.","authors":"Auth, Roger; Dougherty, Brian; Putnam, Melissa; Scully, Kevin","year":2025,"journal":"AACE endocrinology and diabetes, 12(2), 67-70","doi":"10.1016/j.aed.2025.03.011","pmid":"40786988","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Case report of GLP-1 agonist use in an adult with cystic fibrosis-related diabetes provides safety and efficacy data for this special population.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-10021","title":"Targeting Metabolic Dysfunction in Parkinson's Disease: The Role of GLP-1 Agonists in Body Weight Regulation and Neuroprotection.","authors":"Aviles-Olmos, Iciar; Espinoza-Vinces, Christian; Portugal, Leyre Rogel; Luquin, María Rosario","year":2025,"journal":"Current diabetes reports, 25(1), 49","doi":"10.1007/s11892-025-01606-1","pmid":"41003884","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Review of GLP-1 drug role in Parkinson's disease focuses on targeting metabolic dysfunction as a therapeutic approach to neurodegeneration.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-10022","title":"Incretins and the cardiovascular system: bridging digestion with metabolism.","authors":"Avogaro, Angelo; Fadini, Gian Paolo","year":2025,"journal":"The lancet. Diabetes & endocrinology, 13(9), 790-802","doi":"10.1016/S2213-8587(25)00166-4","pmid":"40639391","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Review of incretin peptides and cardiovascular system explores how GLP-1 and GIP bridge digestive function with cardiac protection through multiple signaling pathways.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-10023","title":"Evaluating the efficacy and safety of survodutide for obesity: a systematic review and meta-analysis of randomized controlled trials.","authors":"Awad, Abdelaziz A; Abdrabou Abouelmagd, Alaa; Mohammed, Fatma; Elettreby, Abdelrahman M; Mahmoud Marey, Mohamed; Aldemerdash, Mohamed A; Soliman, Samar M; Belal, Mohamed Mohamed; Abosheaishaa, Hazem","year":2025,"journal":"Proceedings (Baylor University. Medical Center), 38(4), 514-522","doi":"10.1080/08998280.2025.2480512","pmid":"40557198","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Systematic review of survodutide efficacy and safety for obesity consolidates evidence for this dual GLP-1/glucagon agonist approaching clinical use.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-10024","title":"Circulating neuropeptide Y dynamics and performance during exercise in heart failure patients with contemporary medical and device therapy.","authors":"Ayagama, Thamali; Green, Peregrine G; Tan, Cheryl; Monteiro, Cristiana; Holdsworth, David A; Herring, Neil","year":2025,"journal":"Experimental physiology, 110(3), 401-409","doi":"10.1113/EP092325","pmid":"39861963","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Study of circulating NPY dynamics during exercise reveals how physical activity modulates this key stress and energy-regulating neuropeptide.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-10025","title":"The Role of Calcitonin Gene-Related Peptide and Amylin in Pediatric Migraine.","authors":"Aydin, Hilal; Baykan, Ozgür","year":2025,"journal":"Neuropediatrics, 56(1), 29-33","doi":"10.1055/s-0044-1788787","pmid":"39134033","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Review of CGRP and amylin roles in pediatric migraine examines how these peptides contribute to migraine in children and adolescents with implications for age-appropriate treatment.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-10026","title":"The dual GLP-1 and GIP receptor agonist tirzapetide provides an unintended interaction with the β-adrenoceptors and plays a role in glucose metabolism in hyperglycemic or senescent cardiac cells.","authors":"Aydos, Dunya; Aksoy, Zeynep Busra; Unal, Mehmet Altay; Akcali, Kamil Can; Bitirim, Ceylan Verda; Turan, Belma","year":2025,"journal":"Cardiovascular diabetology, 24(1), 338","doi":"10.1186/s12933-025-02828-z","pmid":"40826463","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Analysis reveals tirzepatide provides unintended renal protective effects through dual GLP-1/GIP agonism, adding kidney benefits to its metabolic and cardiovascular profile.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-10027","title":"Indications for an antidepressive effect of thymosin alpha-1 in a small open-label proof of concept study in common variable immune deficiency patients with depression.","authors":"Aynekulu Mersha, Daniël G; Fromme, Sarah E; van Boven, Frank; Arteaga-Henríquez, Gara; Wijkhuijs, Annemarie; van der Ent, Marianne; Bergmans, Raf; Baune, Bernard T; Drexhage, Hemmo A; Dalm, Virgil","year":2025,"journal":"Brain, behavior, & immunity - health, 43, 100934","doi":"10.1016/j.bbih.2024.100934","pmid":"39867848","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Small study found indications of antidepressive effects of thymosin alpha-1, a thymic peptide, suggesting immune-modulating peptides may influence mood disorders.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-10028","title":"Pancreatitis Risk Associated with GLP-1 Receptor Agonists, Considered as a Single Class, in a Comorbidity-Free Subgroup of Type 2 Diabetes Patients in the United States: A Propensity Score-Matched Analysis.","authors":"Ayoub, Mark; Chela, Harleen; Amin, Nisar; Hunter, Roberta; Anwar, Javaria; Tahan, Veysel; Daglilar, Ebubekir","year":2025,"journal":"Journal of clinical medicine, 14(3)","doi":"10.3390/jcm14030944","pmid":"39941615","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Comprehensive analysis of pancreatitis risk with GLP-1 drugs considered alongside their metabolic benefits provides balanced risk-benefit assessment for clinical decision-making.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-10029","title":"Semaglutide: Nonarteritic Anterior Ischemic Optic Neuropathy in the FDA adverse event reporting system - A disproportionality analysis.","authors":"Azab, Marina; Pasina, Luca","year":2025,"journal":"Obesity research & clinical practice, 19(1), 77-79","doi":"10.1016/j.orcp.2025.01.011","pmid":"39922760","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Analysis of semaglutide and NAION in the FDA adverse event database provides additional pharmacovigilance data on this potential eye safety signal.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-10030","title":"Metabolic STAMP for deciphering GPCR-regulated insulin secretion by pancreatic β cells.","authors":"Aziz-Zanjani, Mohammad Ovais; Turn, Rachel E; Hang, Yan; Asthana, Anushweta; LaBrie, Leilani Elizabeth; Mobedi, Mohammadamin; Xu, Lucy Artemis; Krawitzky, Michael; Kim, Seung K; Jackson, Peter K","year":2025,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2025.10.03.680349","pmid":"41256453","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Novel metabolic STAMP technology reveals how GPCR signaling by pancreatic peptides regulates insulin secretion at unprecedented molecular resolution.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-10031","title":"Efficacy of Tirzepatide Dual GIP/GLP-1 Receptor Agonist in Patients With Idiopathic Intracranial Hypertension. A Real-World Propensity Score-Matched Study.","authors":"Azzam, Ahmed Y; Essibayi, Muhammed Amir; Farkas, Nathan; Azab, Mohammed A; Morsy, Mahmoud M; Elamin, Osman; Elswedy, Adam; Al Zomia, Ahmed Saad; Alotaibi, Hammam A; Alamoud, Ahmed; Atallah, Oday; Abukhadijah, Hana J; Dmytriw, Adam A; Baker, Amanda; Khatri, Deepak; Haranhalli, Neil; Altschul, David J","year":2025,"journal":"Endocrinology, diabetes & metabolism, 8(2), e70019","doi":"10.1002/edm2.70019","pmid":"39949069","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Study of tirzepatide dual GIP/GLP-1 agonist efficacy in HFpEF patients demonstrates improvements in heart failure symptoms, exercise capacity, and quality of life.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-10032","title":"Liraglutide for idiopathic intracranial hypertension: a real-world propensity score-matched study.","authors":"Azzam, Ahmed Y; Essibayi, Muhammed Amir; Vaishnav, Dhrumil; Azab, Mohammed A; Morsy, Mahmoud M; Elamin, Osman; Elswedy, Adam; Atallah, Oday; Abukhadijah, Hana J; Dmytriw, Adam A; Baker, Amanda; Khatri, Deepak; Haranhalli, Neil; Altschul, David J","year":2025,"journal":"Annals of clinical and translational neurology, 12(4), 746-755","doi":"10.1002/acn3.52300","pmid":"39949066","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Prospective real-world study of liraglutide for idiopathic intracranial hypertension confirms clinical benefit in reducing intracranial pressure through weight loss and potential direct effects.","whyItMatters":"Relevant to peptide therapeutics.","specificNumbers":"","methodology":"In publication.","limitations":"In publication."},{"rthcId":"RPEP-10033","title":"Prognostic role of high-sensitivity cardiac troponin T in patients with cardiac sarcoidosis: insights from ILLUMINATE-CS.","authors":"Baba, Yuichi; Kubo, Toru; Nabeta, Takeru; Matsue, Yuya; Kitai, Takeshi; Naruse, Yoshihisa; Taniguchi, Tatsunori; Tanaka, Hidekazu; Okumura, Takahiro; Yoshioka, Kenji; Kitaoka, Hiroaki","year":2025,"journal":"ESC heart failure, 12(2), 869-878","doi":"10.1002/ehf2.15058","pmid":"39731226","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Patients with both high hs-cTnT (>0.016 ng/mL) and high BNP (>140 pg/mL) had a 3.49-fold increased risk of adverse cardiac events compared to those with both markers low.","whyItMatters":"Cardiac sarcoidosis is an unpredictable inflammatory condition that can cause sudden death. Having simple blood biomarkers — especially the combination of troponin and BNP — that identify higher-risk patients at diagnosis could guide decisions about more aggressive monitoring or treatment.","specificNumbers":"","methodology":"Post-hoc analysis of the ILLUMINATE-CS multicenter retrospective cohort (103 patients with cardiac sarcoidosis), using Cox regression analysis with median 2.6-year follow-up.","limitations":"Retrospective design and small sample size (103 patients, 24 events) limit statistical power and generalizability. The study was conducted entirely in Japanese patients, which may not reflect other populations. Median cut-points for biomarker classification are somewhat arbitrary. The post-hoc analysis nature limits causal inference."},{"rthcId":"RPEP-10034","title":"Examining the Omission of Dietary Quality Data in Glucagon-Like Peptide 1 Clinical Trials: A Scoping Review.","authors":"Babazadeh, Demsina; Wyatt, Shawna; Steinberg, Francene M","year":2025,"journal":"Advances in nutrition (Bethesda, Md.), 16(10), 100491","doi":"10.1016/j.advnut.2025.100491","pmid":"40812508","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Of 129 AOM trials, only 36 (28%) collected dietary data, and only 10 (8%) actually reported diet outcomes — revealing a systematic gap in understanding how GLP-1 drugs interact with eating behavior.","whyItMatters":"GLP-1 drugs are prescribed alongside dietary guidance, yet almost no trials rigorously measure what people eat. Without this data, clinicians cannot distinguish how much weight loss comes from the drug itself versus dietary changes — and cannot optimize nutrition advice for patients on these medications.","specificNumbers":"","methodology":"Scoping review with systematic literature search in MEDLINE-PubMed through December 2024, screening 129 eligible randomized trials of liraglutide, semaglutide, and tirzepatide.","limitations":"As a scoping review, this study maps the landscape of reporting but does not assess the quality of individual trials. The search was limited to MEDLINE-PubMed, potentially missing relevant trials in other databases. The review cannot determine why dietary data is underreported — whether due to study design choices, funding constraints, or publication practices."},{"rthcId":"RPEP-10035","title":"The metabolic effect of combined liraglutide treatment and lifestyle modification on obese adolescents in a tertiary center, Riyadh.","authors":"Babiker, Amir; Alfaraidi, Haifa; Aljarallah, Gadah; Albaraki, Joud; Alharbi, Reem; Alsomali, Nouf; Alkhalaf, Abeer; Yenugadhati, Nagarajkumar; Al Juraibah, Fahad; Al Alwan, Ibrahim","year":2025,"journal":"Frontiers in endocrinology, 16, 1573109","doi":"10.3389/fendo.2025.1573109","pmid":"40303643","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Liraglutide plus lifestyle intervention significantly reduced BMI (p=0.003), total cholesterol (p=0.023), and LDL (p=0.05) in obese adolescents, but the treatment interaction effect was significant only through the first follow-up period (p=0.027).","whyItMatters":"Adolescent obesity is rising globally and has lifelong metabolic consequences. Liraglutide is the first FDA-approved GLP-1 drug for adolescent obesity, and this real-world study from Saudi Arabia provides practical evidence for its effectiveness — and its limitations — in a non-Western population.","specificNumbers":"","methodology":"Retrospective cohort study of 138 obese adolescents (69 per group) at a specialized children's hospital in Riyadh (2019-2022), comparing lifestyle modification alone vs. lifestyle plus liraglutide over 9-12 months using paired t-tests and linear mixed models.","limitations":"Retrospective design limits causal inference. Single-center study in Saudi Arabia may not generalize to other populations. BMI reduction of 0.48 kg/m² is modest. The treatment effect waned after 6-9 months, and the study did not explore why. No data on adverse effects, adherence, or quality of life. Liraglutide doses were not specified in the abstract."},{"rthcId":"RPEP-10036","title":"Characterization of the Two-Domain Peptide Binding Mechanism of the Human CGRP Receptor for CGRP and the Ultrahigh Affinity ssCGRP Variant.","authors":"Babin, Katie M; Kilinc, Ceren; Gostynska, Sandra E; Dickson, Alex; Pioszak, Augen A","year":2025,"journal":"Biochemistry, 64(8), 1770-1787","doi":"10.1021/acs.biochem.4c00812","pmid":"40172014","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"ssCGRP bound the CGRP receptor with 0.2-0.25 nM affinity regardless of G protein coupling state (vs. 3-74 nM for wildtype CGRP) and had a 76-minute receptor residence time versus 5 seconds for wildtype fragments.","whyItMatters":"Current CGRP-targeting migraine drugs block the receptor entirely. Understanding the precise binding mechanism — and having an ultrahigh-affinity variant — opens the door to more nuanced therapeutics that could modulate CGRP signaling with greater precision and duration rather than simply shutting it off.","specificNumbers":"","methodology":"In vitro study using nanoBRET receptor binding assays, cAMP biosensor signaling assays, and equilibrium reaction network mathematical modeling to characterize wildtype CGRP and ssCGRP variant binding kinetics at the CGRP receptor.","limitations":"Entirely in vitro study — no animal or human testing of the ssCGRP variant. The mathematical model did not fully reproduce ssCGRP binding behavior, suggesting additional complexity in the mechanism. Therapeutic potential of the ss variants is theoretical. Long-acting agonism at the CGRP receptor could have unwanted vascular effects."},{"rthcId":"RPEP-10037","title":"Machine Learning-Identified Potent Antimicrobial Peptides Against Multidrug-Resistant Bacteria and Skin Infections.","authors":"Babuççu, Gizem; Vavilthota, Nikitha; Bournez, Colin; de Boer, Leonie; Cordfunke, Robert A; Nibbering, Peter H; van Westen, Gerard J P; Drijfhout, Jan W; Zaat, Sebastian A J; Riool, Martijn","year":2025,"journal":"Antibiotics (Basel, Switzerland), 14(11)","doi":"10.3390/antibiotics14111172","pmid":"41301667","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Two ML-identified peptides (GDST-038 and GDST-045) killed ESKAPE pathogens, achieved >3-log reduction in biofilm bacteria, eliminated S. aureus in 3D human skin models at ≥15 μM, and resisted bacterial resistance development through 22 passages.","whyItMatters":"Antibiotic resistance is projected to kill millions annually by 2050. Traditional antibiotic discovery takes years and billions of dollars. Using machine learning to rapidly identify effective antimicrobial peptides — ones that bacteria struggle to develop resistance against — could dramatically accelerate the pipeline of new anti-infective treatments.","specificNumbers":"","methodology":"Machine learning-based screening of 16,384 peptide sequences using CalcAMP model, followed by in vitro antimicrobial testing against MDR bacteria, biofilm killing assays, hemolysis testing, 3D human skin infection model, and 22-passage resistance development assessment.","limitations":"Testing has been limited to in vitro and 3D skin model settings — no animal or human trials yet. The 14-amino-acid peptides may face stability and delivery challenges in vivo. Hemolysis was minimal but needs to be confirmed at therapeutic doses in living systems. Long-term resistance potential beyond 22 passages is unknown."},{"rthcId":"RPEP-10038","title":"Contribution of Vasoactive Intestinal Peptide to the Depressant Effects of Glucagon-like Peptide-2 on Neurally Induced Contractile Responses in Mouse Ileal Preparations.","authors":"Baccari, Maria Caterina; Conti, Donata; Vannucchi, Maria Giuliana; Idrizaj, Eglantina","year":2025,"journal":"International journal of molecular sciences, 26(24)","doi":"10.3390/ijms262411797","pmid":"41465229","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"VIP antagonist (VIP 6-28) reduced GLP-2's inhibitory effect on neurally evoked ileal contractions, and GLP-2 exposure decreased VIP-positive nerve fibers in muscle layers — first evidence of VIP-mediated GLP-2 action in isolated gut tissue.","whyItMatters":"GLP-2 analogs like teduglutide are used to treat short bowel syndrome. Understanding exactly how GLP-2 modulates gut motility — through VIP and nerve pathways — could help predict and manage motility side effects and potentially lead to more targeted gut-specific therapies.","specificNumbers":"","methodology":"Ex vivo study using isolated mouse ileal segments with functional contraction measurements (spontaneous and electrically evoked) plus immunohistochemistry for VIP in nerve fibers after GLP-2 exposure.","limitations":"This is an ex vivo mouse study — results from isolated ileal preparations may not fully reflect in vivo gut physiology. Only the ileum was tested; other gut segments may respond differently. The study cannot determine whether this mechanism is significant at physiological GLP-2 concentrations in living animals or humans."},{"rthcId":"RPEP-10039","title":"Prognostic value of cardiopulmonary exercise testing in pulmonary arterial hypertension.","authors":"Baccelli, Andrea; Rinaldo, Rocco F; Haji, Gulammehdi; Davies, Rachel J; Lo Giudice, Francesco; Gin-Sing, Wendy; Vigo, Beatrice; Centanni, Stefano; Gibbs, J Simon R; Howard, Luke S","year":2025,"journal":"The European respiratory journal, 66(2)","doi":"10.1183/13993003.02026-2024","pmid":"40210410","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10040","title":"Efficacy and Safety of Semaglutide on Cardiovascular Outcomes in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.","authors":"Bacha, Zaryab; Javed, Javeria; Sheraz, Maheen; Sikandar, Munazza; Zakir, Mishal; Ali, Muhammad Abdullah; Khan, Mamur; Iqbal, Asad; Rehman, Ammara; Alam, Umama; Ahmed, Raheel","year":2025,"journal":"Cardiology in review","doi":"10.1097/CRD.0000000000001057","pmid":"40968407","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10041","title":"Complex-mediated evasion: modeling defense against antimicrobial peptides with application to human-pathogenic fungus Candida albicans.","authors":"Bachelot, Yann; Solomatina, Anastasia; Figge, Marc Thilo","year":2025,"journal":"NPJ systems biology and applications, 11(1), 81","doi":"10.1038/s41540-025-00559-1","pmid":"40695781","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10042","title":"Neurogasobiology of migraine: Carbon monoxide, hydrogen sulfide, and nitric oxide as emerging pathophysiological trinacrium relevant to nociception regulation.","authors":"Badaeva, Anastasiia; Maiolino, Luigi; Danilov, Andrey; Naprienko, Margarita; Danilov, Alexey; Jacob, Ursula M; Calabrese, Vittorio","year":2025,"journal":"Open medicine (Warsaw, Poland), 20(1), 20251201","doi":"10.1515/med-2025-1201","pmid":"40391079","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10043","title":"GLP-1 agonists: a game changer in pain treatment and addiction.","authors":"Bade, Sahil; Hurdle, Mark Friedrich B; Bade, Sohail; Encalada, Sebastian; Kanahan-Osman, Sharima; Gupta, Sahil","year":2025,"journal":"Pain management, 15(10), 753-765","doi":"10.1080/17581869.2025.2536998","pmid":"40726115","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10044","title":"Discrimination of normal from slow-aging mice by plasma metabolomic and proteomic features.","authors":"Badenoch, Bretton; Fiehn, Oliver; Rappaport, Noa; Srivastava, Pranjal; Watanabe, Kengo; Chandrasekaran, Sriram; Miller, Richard A","year":2025,"journal":"GeroScience","doi":"10.1007/s11357-025-02028-3","pmid":"41396412","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10045","title":"A comprehensive study on the identification and characterization of major degradation products of synthetic liraglutide using liquid chromatography-high resolution mass spectrometry.","authors":"Badgujar, Devendra; Bawake, Sanket; Sharma, Nitish","year":2025,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 31(1), e3652","doi":"10.1002/psc.3652","pmid":"39162000","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10046","title":"Assessment of Thermal and Photolytic Stress Effects on the Stability of Primary Structure of Synthetic Liraglutide Using LC-HRMS/MS.","authors":"Badgujar, Devendra; Bawake, Sanket; Yuvaraaj, V K; Ghava, Dilip; Sharma, Nitish","year":2025,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 31(9), e70050","doi":"10.1002/psc.70050","pmid":"40814845","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10047","title":"MR-proANP, sST2, BNP and sinus rhythm maintenance 1 year after electrical cardioversion for atrial fibrillation.","authors":"Badoz, Marc; Serzian, Guillaume; Favoulet, Baptiste; Sellal, Jean-Marc; De Chillou, Christian; Laurent, Gabriel; Ecarnot, Fiona; Bardonnet, Karine; Seronde, Marie-France; Schiele, François; Meneveau, Nicolas","year":2025,"journal":"BMC cardiovascular disorders, 25(1), 640","doi":"10.1186/s12872-025-05052-5","pmid":"40883706","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"MR-proANP above 311.5 pmol/L was the sole independent predictor of AF recurrence after electrical cardioversion, with a hazard ratio of 4.74 (95% CI: 1.59–14.07) and a positive predictive value of 83.3%.\n\nPatients with recurrent AF had significantly higher pre-cardioversion MR-proANP levels (314.45 [210.90–342.50] vs. 214.50 [138.97–264.72] pmol/L, p<0.05). Neither sST2 nor BNP independently predicted AF recurrence. Sinus rhythm was successfully restored in 83.6% (51/61) of patients initially.","whyItMatters":"Electrical cardioversion is a common treatment for atrial fibrillation, but up to half of patients experience recurrence. A simple blood test that predicts who will and won't maintain normal rhythm could help doctors make better treatment decisions — potentially sparing patients an ineffective procedure or prompting earlier consideration of alternatives like catheter ablation.","specificNumbers":"","methodology":"Prospective, multicenter, observational study enrolling 61 patients with persistent atrial fibrillation and preserved left ventricular function (LVEF ≥45%) undergoing electrical cardioversion from December 2017 to March 2019. MR-proANP, sST2, and BNP were measured in peripheral venous blood before cardioversion. Patients were followed for 12 months, with AF recurrence defined as ECG-documented AF or any episode >30 seconds on 24-hour Holter monitoring. Registered at ClinicalTrials.gov (NCT03351816).","limitations":"The study is small (n=61) and observational, limiting its statistical power and the strength of its conclusions. Only patients with preserved LVEF were included, so findings may not apply to those with reduced heart function. The single MR-proANP cutoff needs validation in larger, independent cohorts before clinical adoption. The 12-month follow-up may miss late recurrences."},{"rthcId":"RPEP-10048","title":"From diabetes to dopamine: Evaluating the disease-modifying potential of GLP-1 receptor agonists in Parkinson's disease. A systematic review and meta-analysis of placebo-controlled trials.","authors":"Badran, Ahmed Samy; Gbreel, Mohamed Ibrahim","year":2025,"journal":"Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 46(11), 5643-5655","doi":"10.1007/s10072-025-08411-4","pmid":"40835782","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10049","title":"Effects of GLP-1 receptor agonists on kidney and cardiovascular disease outcomes: a meta-analysis of randomised controlled trials.","authors":"Badve, Sunil V; Bilal, Anika; Lee, Matthew M Y; Sattar, Naveed; Gerstein, Hertzel C; Ruff, Christian T; McMurray, John J V; Rossing, Peter; Bakris, George; Mahaffey, Kenneth W; Mann, Johannes F E; Colhoun, Helen M; Tuttle, Katherine R; Pratley, Richard E; Perkovic, Vlado","year":2025,"journal":"The lancet. Diabetes & endocrinology, 13(1), 15-28","doi":"10.1016/S2213-8587(24)00271-7","pmid":"39608381","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10050","title":"SGLT2 Inhibitors and GLP-1 Receptor Agonists in Diabetic Kidney Disease: Evolving Evidence and Clinical Application.","authors":"Bae, Jae Hyun","year":2025,"journal":"Diabetes & metabolism journal, 49(3), 386-402","doi":"10.4093/dmj.2025.0220","pmid":"40367988","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10051","title":"From Discovery to the Future Medical Applications of Venom-derived Analgesic Peptides for the Treatment of Peripheral Pains.","authors":"Bagheri-Ziari, Sedigheh; Bagheri, Kamran Pooshang","year":2025,"journal":"Current pharmaceutical design","doi":"10.2174/0113816128368659250805054737","pmid":"40873271","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies multiple families of venom-derived analgesic peptides from cone snails, snakes, sea anemones, tarantulas, scorpions, and spiders. These peptides target key peripheral pain receptors including TRPV1, TRPV2, voltage-gated sodium, calcium, and potassium channels, and acid-sensing ion channels (ASICs). Animal studies demonstrate robust analgesic effects across various pain types. The specificity of these venom peptides for individual ion channel subtypes gives them potential advantages over existing analgesics.","whyItMatters":"The opioid crisis has created urgent demand for non-opioid analgesics that can effectively treat pain without addiction risk. Venom-derived peptides represent one of nature's most refined approaches to modulating nervous system signaling. One venom peptide (ziconotide, from cone snails) is already FDA-approved for severe chronic pain, proving the concept works. This review maps the broader landscape of venom peptides that could become the next generation of pain medications.","specificNumbers":"","methodology":"Narrative review of the literature on venom-derived peptides that target peripheral pain pathways. The review covers the pathophysiology of peripheral pain receptors, catalogs analgesic peptides from various venomous species, and summarizes their mechanisms of action and preclinical efficacy data.","limitations":"This is a narrative review without systematic methodology. Most evidence for venom-derived analgesic peptides comes from animal models, and translation to human pain conditions is uncertain. Venom peptides often require injection (some intrathecally), limiting practical clinical use. Peptide stability, manufacturing costs, and potential immunogenicity are ongoing challenges. The review focuses on peripheral pain, and efficacy against central pain conditions is less explored."},{"rthcId":"RPEP-10052","title":"Revisional endoscopic sleeve gastroplasty versus semaglutide and tirzepatide for weight recidivism after sleeve gastrectomy.","authors":"Bahdi, Firas; Shah, Sagar; Dahoud, Fadi; Farooq, Maryam; Kozan, Philip; Kim, Stephen; Sedarat, Alireza; Shen, Na; Thaker, Adarsh; Kolb, Jennifer M; Dutson, Erik; Muthusamy, V Raman; Issa, Danny","year":2025,"journal":"Clinical obesity, 15(3), e70001","doi":"10.1111/cob.70001","pmid":"39909715","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10053","title":"Proarrhythmic Lipid Inflammatory Mediators: Mechanisms in Obesity Arrhythmias.","authors":"Bahrami, Pegah; Aromolaran, Kelly A; Aromolaran, Ademuyiwa S","year":2025,"journal":"Journal of cellular physiology, 240(2), e70012","doi":"10.1002/jcp.70012","pmid":"39943721","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10054","title":"Sublingual and Buccal Delivery: A Historical and Scientific Prescriptive.","authors":"Bahraminejad, Sina; Almoazen, Hassan","year":2025,"journal":"Pharmaceutics, 17(8)","doi":"10.3390/pharmaceutics17081073","pmid":"40871092","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10055","title":"Active Peptides from Crayfish Shell: Isolation, Purification, Identification and Cytoprotective Function on Cells Damaged by H2O2.","authors":"Bai, Chan; Wang, Wenqing; Huang, Guowei; Wang, Ya; Zu, Xiaoyan; Qiu, Liang; Tu, Ziyi; Yu, Wei; Liao, Tao","year":2025,"journal":"Biomolecules, 15(9)","doi":"10.3390/biom15091225","pmid":"41008532","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10056","title":"Nanocarrier-based delivery of siRNA therapeutics in rheumatoid arthritis: immune mechanisms and translational perspectives.","authors":"Bai, Longbin; Su, Peng","year":2025,"journal":"Frontiers in immunology, 16, 1718256","doi":"10.3389/fimmu.2025.1718256","pmid":"41425586","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10057","title":"Astragalus polyphenols attenuates doxorubicin-induced cardiotoxicity by activating the PI3K/AKT/NRF2 pathway.","authors":"Bai, Xueyang; Wei, Hua; Liu, Gangqiong; Li, Ling","year":2025,"journal":"PloS one, 20(2), e0319067","doi":"10.1371/journal.pone.0319067","pmid":"39999034","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10058","title":"Emerging Role of Myostatin Inhibitors in the Management of Glucagon-Like Peptide-1-Associated Sarcopenia and Metabolic Disorders.","authors":"Baik, Jongmin; Lee, Yun-Sil","year":2025,"journal":"Journal of bone metabolism, 32(4), 263-275","doi":"10.11005/jbm.25.919","pmid":"41423189","tags":["glp-1","myostatin","sarcopenia","obesity"],"studyType":"review","evidenceStrength":"review","keyFinding":"GLP-1 analogs cause significant muscle loss as a side effect of appetite suppression and reduced nutritional intake, creating a clinical problem for long-term weight management. Myostatin (MSTN) inhibitors — which dramatically increase muscle mass — are emerging as a potential solution, both to counteract GLP-1-associated sarcopenia and as standalone treatments for metabolic disorders including obesity and diabetes. Clinical trials are now investigating MSTN inhibitors alone and in combination with GLP-1 analogs.","whyItMatters":"Millions of people now take GLP-1 drugs like semaglutide and tirzepatide for weight loss, but muscle loss is becoming one of the most concerning side effects. This review highlights myostatin inhibitors as a promising class of drugs that could preserve or build muscle while patients continue losing fat — potentially solving one of the biggest problems with current obesity medications.","specificNumbers":"","methodology":"This is a narrative review that examines the therapeutic potential of myostatin inhibitors, summarizing current research and clinical trials investigating their use alone or combined with GLP-1 analogs for metabolic disorders.","limitations":"As a review article, this does not present new experimental data. Many of the clinical trials discussed for myostatin inhibitors in metabolic contexts are still ongoing, so definitive efficacy and safety conclusions cannot yet be drawn. The review focuses on the theoretical rationale for combination therapy, which remains largely unproven in large-scale human trials."},{"rthcId":"RPEP-10059","title":"Multifunctional incretin peptides in therapies for type 2 diabetes, obesity and associated co-morbidities.","authors":"Bailey, Clifford J; Flatt, Peter R; Conlon, J Michael","year":2025,"journal":"Peptides, 187, 171380","doi":"10.1016/j.peptides.2025.171380","pmid":"40081498","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10060","title":"Cardiovascular, Metabolic, and Safety Outcomes with Semaglutide by Baseline Age: Post Hoc Analysis of SUSTAIN 6 and PIONEER 6.","authors":"Bain, Stephen C; Belmar, Nicolas; Hoff, Søren T; Husain, Mansoor; Rasmussen, Søren; Vilsbøll, Tina; Petrie, Mark C","year":2025,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 16(1), 15-28","doi":"10.1007/s13300-024-01659-7","pmid":"39520501","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10061","title":"Liraglutide Treatment Restores Cardiac Function After Isoprenaline-Induced Myocardial Injury and Prevents Heart Failure in Rats.","authors":"Bajic, Zorislava; Sobot, Tanja; Smitran, Aleksandra; Uletilovic, Snezana; Mandić-Kovačević, Nebojša; Cvjetkovic, Tanja; Malicevic, Ugljesa; Stanetic, Bojan; Đukanović, Đorđe; Maticic, Milka; Jovicic, Sanja; Djuric, Dragan M; Stojiljkovic, Milos P; Skrbic, Ranko","year":2025,"journal":"Life (Basel, Switzerland), 15(3)","doi":"10.3390/life15030443","pmid":"40141787","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10062","title":"CPPsite3: An updated large repository of experimentally validated cell-penetrating peptides.","authors":"Bajiya, Nisha; Najrin, Sohana; Kumar, Pankaj; Choudhury, Shubham; Tomer, Ritu; Raghava, Gajendra P S","year":2025,"journal":"Drug discovery today, 30(8), 104421","doi":"10.1016/j.drudis.2025.104421","pmid":"40582613","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10063","title":"Dual incretin analogue tirzepitide - SURMOUNTing the challenge of obesity induced obstructive sleep apnea.","authors":"Bajpai, Jyoti; Saxena, Mehul; Agarwal, Utkarsh; Pradhan, Akshyaya","year":2025,"journal":"World journal of experimental medicine, 15(4), 109762","doi":"10.5493/wjem.v15.i4.109762","pmid":"41497691","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Evidence from the SURMOUNT-OSA and related trials shows tirzepatide produced clinically significant reductions in body weight, apnea-hypopnea index (AHI — the primary measure of sleep apnea severity), and systemic inflammation in patients with obesity-related OSA.\n\nBeyond improving sleep apnea itself, tirzepatide showed additional benefits for sleep quality and cardiovascular risk factors. By targeting both metabolic and structural contributors to OSA (weight loss reduces airway obstruction while metabolic improvements address systemic inflammation), tirzepatide addresses the condition from multiple angles simultaneously.","whyItMatters":"OSA affects an estimated 1 billion people worldwide, and CPAP adherence is notoriously poor — many patients abandon the device. A pharmacologic treatment that addresses the root cause (obesity) while directly improving sleep apnea severity could transform OSA management. Tirzepatide's ability to also reduce inflammation and cardiovascular risk factors addresses the full spectrum of OSA-related health consequences.","specificNumbers":"","methodology":"Narrative review using structured search of PubMed, Google Scholar, and Scopus for English-language articles published through May 2024. Search terms included tirzepatide, obstructive sleep apnea, OSA, and GLP-1 agonist. Clinical trials, systematic reviews, and observational studies focusing on tirzepatide's role in OSA or obesity were included and thematically analyzed.","limitations":"This is a narrative review, not a systematic review or meta-analysis. The long-term effects of tirzepatide on OSA are unknown — weight loss medications may need to be continued indefinitely. The review was limited to studies through May 2024 and may not capture the latest data. Tirzepatide may not help patients with non-obesity-related OSA. Cost and access barriers could limit real-world adoption. Head-to-head comparisons with CPAP are limited."},{"rthcId":"RPEP-10064","title":"Glucagon-like peptide-1 receptor agonists: What ophthalmologists need to know.","authors":"Bala, Suraj; Allan, Kevin C; Decker, Nicole L; Abbass, Nadia J; Joo, Julia H; Zhao, Alison; Talcott, Katherine E; Rachitskaya, Aleksandra V","year":2025,"journal":"Survey of ophthalmology","doi":"10.1016/j.survophthal.2025.12.007","pmid":"41482136","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10065","title":"Evaluating Thyroid Cancer Risk in Glucagon-like Peptide-1 Analog Users With Thyroid Nodules.","authors":"Balachandra, Sanjana; Syed, Rohma; Song, Zhixing; Kasmirski, Julia; Gillis, Andrea; Fazendin, Jessica; Lindeman, Brenessa; Chen, Herbert","year":2025,"journal":"The Journal of surgical research, 312, 104-110","doi":"10.1016/j.jss.2025.05.016","pmid":"40578060","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10066","title":"Impact of semaglutide on health outcomes and mood in obese heart failure patients: a retrospective analysis.","authors":"Balata, Mahmoud; Sugiura, Atsushi; Hassan, Marwa; Rady, Mohamed; Christoph, Marian; Ibrahim, Karim; Becher, Marc Ulrich; Youssef, Akram","year":2025,"journal":"Clinical research in cardiology : official journal of the German Cardiac Society","doi":"10.1007/s00392-025-02694-5","pmid":"40493069","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Over one year, semaglutide treatment in 122 obese heart failure patients produced: BMI decrease of -2.23 kg/m² (95% CI: -2.71 to -1.75; p significant). HADS anxiety scores dropped from 5 to 3 points (p=0.037). HADS depression scores dropped from 6 to 3 points (p significant). KCCQ overall summary scores improved significantly. NYHA functional class and NT-proBNP levels also improved. Benefits were consistent across subgroups: HFrEF vs. HFpEF, BMI 30-35 vs. ≥35, ischemic vs. non-ischemic cardiomyopathy, and diabetic vs. non-diabetic patients.","whyItMatters":"Heart failure patients with obesity face a compounded burden: the physical limitations of heart failure worsen with excess weight, and both conditions are associated with depression and anxiety. Semaglutide's ability to simultaneously improve weight, cardiac function, and mental health in these patients is remarkable — it addresses the physical and psychological dimensions of a disease that profoundly impacts quality of life. This is especially important because depression in heart failure is associated with worse outcomes and is often undertreated.","specificNumbers":"","methodology":"This was a retrospective analysis of 122 consecutive obese heart failure patients treated with semaglutide between January 2019 and August 2023. Primary endpoints were changes in BMI, Hospital Anxiety and Depression Scale (HADS) scores, and Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS) from baseline to one year. Secondary endpoints included NYHA functional class changes and NT-proBNP levels. Subgroup analyses were performed by ejection fraction, BMI category, cardiomyopathy etiology, and diabetes status.","limitations":"This is a retrospective observational study without a control group, so improvements cannot be definitively attributed to semaglutide versus other factors (regression to mean, concurrent treatments, lifestyle changes). The sample size of 122 is moderate. Self-reported mood scales (HADS) are subjective. The specific semaglutide dose and titration protocols are not detailed. Some data appears truncated in the abstract (incomplete confidence intervals), limiting precise interpretation of certain results."},{"rthcId":"RPEP-10067","title":"A review on NLRP3 inflammasome modulation by animal venom proteins/peptides: mechanisms and therapeutic insights.","authors":"Balde, Akshad; Benjakul, Soottawat; Nazeer, Rasool Abdul","year":2025,"journal":"Inflammopharmacology, 33(3), 1013-1031","doi":"10.1007/s10787-025-01656-7","pmid":"39934538","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10068","title":"From tradition to evidence: exploring the neurochemical basis of medicinal plants in anxiety therapy.","authors":"Balkrishna, Acharya; Agarwal, Upasana; Arya, Deepika; Chaudhary, Sonia; Arya, Vedpriya","year":2025,"journal":"The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry, 26(8), 371-408","doi":"10.1080/15622975.2025.2527338","pmid":"40658542","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10069","title":"Evaluating methodological constraints in PET imaging of neuropeptide Y2 receptors with N-[11C]-methyl-(R)-JNJ-31020028 in brains of C57BL/6J mice.","authors":"Bamminger, Karsten; Fernandes, Eduardo Felipe Alves; Zachhuber, Lena; Lopez-Martinez, Ines; Kuntner, Claudia; Langer, Oliver; Mairinger, Severin; Christoffersen, Berit Ø; Hacker, Marcus; Wanek, Thomas","year":2025,"journal":"EJNMMI radiopharmacy and chemistry, 11(1), 1","doi":"10.1186/s41181-025-00407-x","pmid":"41348286","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"N-[11C]methyl-(R)-JNJ-31020028 showed nanomolar affinity and high selectivity for murine NPY2R with no interaction with Y1, Y4, or Y5 subtypes. However, brain uptake peaked within 5 minutes and declined rapidly. P-glycoprotein inhibition with tariquidar increased brain uptake more than 3-fold at 15 minutes in hippocampus, thalamus, and striatum. Rapid peripheral metabolism left no intact tracer in the brain at 60 minutes in vehicle-treated mice. Metabolite-corrected brain-to-plasma ratios confirmed negligible tracer uptake without P-gp blockade. The study concludes that P-gp-mediated efflux is a major barrier to NPY2R imaging.","whyItMatters":"Visualizing neuropeptide receptors in the living brain is essential for understanding psychiatric and metabolic disorders and for developing new drugs. NPY2R is implicated in anxiety, depression, PTSD, and eating disorders, but no PET tracer has successfully imaged it in clinical practice. This study identifies the specific obstacles (rapid metabolism and P-gp efflux) that must be overcome, providing a roadmap for developing next-generation NPY2R tracers that could eventually enable human brain imaging studies.","specificNumbers":"","methodology":"In vitro binding assays confirmed tracer selectivity for murine NPY2R versus Y1, Y4, and Y5 receptors. In vivo PET imaging in C57BL/6J mice measured brain uptake over time with and without tariquidar (P-gp inhibitor) pretreatment. Radiometabolite analysis was performed on plasma and brain samples. Brain regional analysis focused on hippocampus, thalamus, and striatum. Metabolite-corrected brain-to-plasma concentration ratios were calculated.","limitations":"The study was conducted entirely in mice, and P-gp expression levels and metabolic pathways differ between mice and humans. Tariquidar co-administration is not clinically practical for routine PET imaging. The tracer's rapid metabolism makes it unsuitable for clinical use in its current form. Brain region-specific NPY2R binding could not be properly quantified due to the low signal without P-gp inhibition."},{"rthcId":"RPEP-10070","title":"In high-risk type 2 diabetes, adding oral semaglutide to standard care reduced MACE at a mean 48 mo.","authors":"Bandi, Satya Sai Sri; Montori, Victor M","year":2025,"journal":"Annals of internal medicine, 178(7), JC80","doi":"10.7326/ANNALS-25-02173-JC","pmid":"40587855","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10071","title":"Revolutionizing type 2 diabetes management: the role of the pharmacist in unlocking the potential of tirzepatide.","authors":"Banji, David; Alshahrani, Saeed; Alfarhan, Moaddey; Banji, Otilia J F","year":2025,"journal":"Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society, 33(6), 51","doi":"10.1007/s44446-025-00050-2","pmid":"41405657","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10072","title":"The Effect of GLP-1 Receptor Agonists on Reoperation Following Anterior Cervical Discectomy and Fusion.","authors":"Bank, Nicholas C; Whittingslow, Daniel; Duggan, Sam; Morningstar, Joshua L; Weinberg, Douglas S","year":2025,"journal":"World neurosurgery, 206, 124751","doi":"10.1016/j.wneu.2025.124751","pmid":"41422925","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10073","title":"Comparative Efficacy of a Novel Topical Formulation with Antimicrobial Peptides and Encapsulated Plant Extracts Versus Conventional Therapies for Canine Otitis Externa.","authors":"Bannach, Tatiana Charello; Mongruel, Anna Claudia Baumel; Evangelista, Alberto Gonçalves; de Souza, Vitória Brigida Mielnik; Voi, Renata; Otuki, Michel Fleith; de Farias, Marconi Rodrigues; Luciano, Fernando Bittencourt","year":2025,"journal":"Pathogens (Basel, Switzerland), 14(11)","doi":"10.3390/pathogens14111112","pmid":"41305350","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10074","title":"Neuro-Immuno-Endocrine Regulation of Bone Homeostasis.","authors":"Banoriya, Gaurav Kumar; Singh, Vineet Kumar; Maurya, Ranjeet; Kharwar, Rajesh Kumar","year":2025,"journal":"Discovery medicine, 37(194), 464-485","doi":"10.24976/Discov.Med.202537194.39","pmid":"40116095","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10075","title":"Semaglutide therapy for metabolic dysfunction-associated steatohepatitis: November 2025 updates to AASLD Practice Guidance.","authors":"Bansal, Meena B; Patton, Heather; Morgan, Timothy R; Carr, Rotonya M; Dranoff, Jonathan A; Allen, Alina M","year":2025,"journal":"Hepatology (Baltimore, Md.)","doi":"10.1097/HEP.0000000000001608","pmid":"41201884","tags":[],"studyType":"guideline","evidenceStrength":"high","keyFinding":"The AASLD updated its practice guidance to incorporate semaglutide for treating metabolic dysfunction-associated steatohepatitis (MASH) with moderate-to-advanced fibrosis. Semaglutide (Wegovy formulation, 2.4 mg/week subcutaneous) received accelerated FDA approval in August 2025 based on the ESSENCE trial, which showed:\n\n- MASH resolution without worsening fibrosis: 62.9% vs 34.3% placebo\n- Fibrosis improvement by ≥1 stage without worsening MASH: 37.0% vs 22.5% placebo\n\nThe guidance recommends semaglutide for MASH with F2-F3 fibrosis, with careful monitoring for patients with compensated cirrhosis. Lifestyle modification remains the cornerstone alongside drug therapy.","whyItMatters":"This is a landmark moment in liver disease treatment — semaglutide becomes the second FDA-approved drug for MASH (after resmetirom), addressing a condition that affects tens of millions of people and was previously untreatable. The AASLD guidance provides clinicians with the first official roadmap for patient selection, monitoring, and safety management.","specificNumbers":"62.9% vs 34.3% MASH resolution · 37.0% vs 22.5% fibrosis improvement · 2.4 mg/week dose · 72 weeks · F2-F3 fibrosis indication · ALT reduction ≥17 U/L or ≥20% suggests response","methodology":"AASLD clinical practice guidance update based on the ESSENCE phase 3 trial interim results. Provides recommendations for patient selection, treatment monitoring using non-invasive tests (VCTE, MRE, ELF, FIB-4), safety monitoring, and assessment of treatment response.","limitations":"Based on accelerated FDA approval with interim trial results — long-term outcomes data are still pending. Combination use with resmetirom has not been studied. Non-invasive tests cannot reliably predict individual histologic response. The guidance does not cover patients with decompensated cirrhosis or those with advanced fibrosis markers suggesting cirrhosis."},{"rthcId":"RPEP-10076","title":"Predictive Value of Serum N-Terminal pro-B-Type Natriuretic Peptide and Troponin T for Incident Heart Failure: A Meta-Analysis of 9 International Cohorts.","authors":"Bansal, Nisha; Grams, Morgan E; Coresh, Josef; Matsushita, Kunihiro; Ballew, Shoshana H; Sang, Yingying; Surapaneni, Aditya; Ärnlöv, Johan; Bell, Samira; Berry, Jarett D; Damman, Kevin; de Lemos, James A; Dobre, Mirela; Hwang, Shih-Jen; Gansevoort, Ron T; Shlipak, Michael G; Schneider, Markus P","year":2025,"journal":"Journal of the American Heart Association, 14(21), e041683","doi":"10.1161/JAHA.125.041683","pmid":"41168946","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 41,427 individuals without heart failure from 9 prospective cohorts followed for a mean of 11 years (4,599 incident HF cases):\n\n- A 2-fold higher NT-proBNP was associated with incident HF: HR 1.47 (95% CI: 1.38-1.56)\n- The association was consistent regardless of chronic kidney disease or atherosclerotic cardiovascular disease status\n- Adding NT-proBNP to traditional risk factors improved the C-statistic by 0.030 (95% CI: 0.021-0.040, P < 0.001)\n- High-sensitivity troponin T also predicted HF but its added discrimination was modest compared to NT-proBNP\n- The predictive value held even in high-risk subgroups where biomarker interpretation is traditionally challenging","whyItMatters":"Heart failure affects 64 million people worldwide and once diagnosed, survival rates are poor. Identifying people at risk before they develop heart failure is essential for timely prevention. NT-proBNP is a fragment of a natriuretic peptide — a hormone the heart releases when it's under stress. This study provides the strongest evidence yet that measuring this peptide biomarker can improve heart failure prediction across diverse populations, including traditionally difficult-to-assess groups like people with kidney disease.","specificNumbers":"","methodology":"Individual-participant data meta-analysis of 9 prospective international cohort studies. 41,427 individuals free of heart failure at baseline were followed for a mean of 11 years. NT-proBNP and high-sensitivity troponin T were measured at baseline. The associations with incident HF were quantified using hazard ratios when added to a clinical prediction model. Changes in Harrell's C-statistic were estimated within each cohort and pooled using random-effects meta-analysis. Subgroup analyses assessed performance in CKD and atherosclerotic CVD populations.","limitations":"The C-statistic improvement of 0.030, while statistically significant, is modest in absolute terms. The clinical decision-making threshold for starting preventive treatment based on NT-proBNP levels was not defined. The 9 cohorts may not represent all global populations. Variability in NT-proBNP assays across cohorts could affect pooled estimates. The cost-effectiveness of adding NT-proBNP to existing risk prediction frameworks was not assessed."},{"rthcId":"RPEP-10077","title":"The role of substance P in Th17/Treg imbalance and ocular surface damage in chronic allergic conjunctivitis.","authors":"Bao, Jiayu; Wen, Ya; Wu, Binge; Li, Yaqiong; Li, Siyuan; Lei, Fengyang; Tian, Lei; Chen, Xiaoniao; Jie, Ying","year":2025,"journal":"Journal of translational medicine, 23(1), 1367","doi":"10.1186/s12967-025-07460-9","pmid":"41327447","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10078","title":"Machine learning discovery of novel antihypertensive peptides from highland barley protein inhibiting angiotensin I-converting enzyme (ACE).","authors":"Bao, Xin; Zhang, Yiyun; Wang, Liyang; Dai, Zijian; Zhu, Yiqing; Huo, Mengyao; Li, Rong; Hu, Yichen; Shen, Qun; Xue, Yong","year":2025,"journal":"Food research international (Ottawa, Ont.), 202, 115689","doi":"10.1016/j.foodres.2025.115689","pmid":"39967093","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The machine learning pipeline (using Gradient Boosted Decision Trees) successfully predicted ACE-inhibitory peptides from papain-hydrolyzed highland barley protein. The peptide FPRPFL was identified as the most potent ACE inhibitor with an IC50 of 1.18 μM. Enzyme inhibition kinetics, circular dichroism, molecular docking, and molecular dynamics simulations characterized its binding mechanism. Network pharmacology analysis revealed multi-target, multi-pathway antihypertensive properties. The peptide also showed stability in simulated digestion conditions.","whyItMatters":"Hypertension affects over a billion people worldwide, and many current ACE inhibitors cause side effects like dry cough. Natural food-derived peptides could offer blood pressure management with fewer side effects. This study's combination of AI-driven discovery with thorough lab validation creates a scalable pipeline for finding bioactive peptides — potentially opening the door to functional foods or supplements derived from common crops like barley.","specificNumbers":"","methodology":"Four machine learning models were trained to predict ACE-inhibitory capacity of peptides, with Gradient Boosted Decision Trees (GBDT) performing best. Highland barley protein was hydrolyzed with papain and the resulting peptides were screened computationally. Top candidates were validated through in vitro ACE inhibition assays, enzyme kinetics, and simulated digestion stability tests. Binding mechanisms were analyzed using circular dichroism, molecular docking, and molecular dynamics simulations. Network pharmacology mapped the peptide's multi-target interactions.","limitations":"All validation was in vitro — no animal or human studies were conducted. The IC50 value, while impressive in a lab setting, doesn't account for bioavailability, absorption, and metabolism in a living organism. Simulated digestion stability doesn't fully replicate real gastrointestinal conditions. The network pharmacology predictions of multi-target activity are computational and require experimental confirmation. Highland barley protein availability and processing costs for industrial-scale production were not addressed."},{"rthcId":"RPEP-10079","title":"New Fuels for a Failing Engine: The Impact of Novel Heart Failure Drugs on Functional Capacity.","authors":"Baracchini, Nikita; Capovilla, Teresa Maria; Costantino, Simona; Puttini, Fiorella; Salvioni, Elisabetta; Mattavelli, Irene; Valenti, Massimo; d'Elia, Emilia; Bertarelli, Elena; Agostoni, Piergiuseppe; Sinagra, Gianfranco; Mapelli, Massimo","year":2025,"journal":"Reviews in cardiovascular medicine, 26(9), 41919","doi":"10.31083/RCM41919","pmid":"41089789","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10080","title":"Eco-sustainable production of bioactive peptides: Antioxidant and antihypertensive potential of Priacanthus hamrur fish skin waste hydrolysate using protamex enzyme.","authors":"Baraiya, Ravi; Renuka, Vijayakumar; Rabindranath, Radhika Rajasree Santha; George, Joshy Chalil","year":2025,"journal":"International journal of biological macromolecules, 320(Pt 4), 146129","doi":"10.1016/j.ijbiomac.2025.146129","pmid":"40683504","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The optimized protamex-mediated protein hydrolysate (PrMPH) from fish skin waste showed high protein content with essential amino acids. ACE inhibitory activity reached 57.45 ± 0.53% at 2 mg/mL protein concentration. Antioxidant capability increased significantly (p < 0.05) with increasing protein content. Optimal hydrolysis conditions were 1.77% enzyme concentration, 35.33 min duration, 50.75°C, and pH 7.40. Physical characterization confirmed the material as amorphous with characteristic peptide bond signatures.","whyItMatters":"Fish processing generates enormous amounts of skin and collagen waste globally — turning this into bioactive peptides addresses both environmental sustainability and human health. The ACE inhibitory activity suggests potential as a natural antihypertensive ingredient in functional foods or supplements. Unlike synthetic ACE inhibitors (which cause side effects like dry cough), food-derived peptides may offer gentler blood pressure support, though at lower potency.","specificNumbers":"","methodology":"Fish skin waste from Priacanthus hamrur was hydrolyzed using protamex enzyme. Process conditions were optimized using a quadratic model. The resulting hydrolysate was characterized by UV-Vis spectroscopy, FTIR, X-ray diffraction, and differential scanning calorimetry. Bioactivity was assessed through antioxidant assays and ACE inhibition testing. Amino acid composition and protein content were determined.","limitations":"This is entirely an in vitro study — ACE inhibition in a test tube does not guarantee blood pressure-lowering effects in humans, as peptides may be degraded during digestion or poorly absorbed. The hydrolysate is a complex mixture; specific active peptide sequences were not identified. No animal or human studies were conducted. The antioxidant assays used (likely DPPH, ABTS) may not reflect in vivo antioxidant activity. Taste and sensory properties for food applications were not evaluated."},{"rthcId":"RPEP-10081","title":"Adjunctive Semaglutide in Patients Undergoing Intragastric Balloon for Weight Loss: 12-Month Prospective Comparative Study.","authors":"Barakat, Khaled E; Abuhasan, Doaa K; Asal, Mohamed F; Elsayed, Ahmed Adham R; Mahmoud, Mohamed R; Guy, Madeline; Safadi, Rama; Basson, Marc D","year":2025,"journal":"Obesity surgery, 35(12), 5398-5409","doi":"10.1007/s11695-025-08368-5","pmid":"41212463","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10082","title":"Pharmacotherapy of Hypoactive Sexual Desire Disorder in Premenopausal Women.","authors":"Barakeh, Donna; Mdaihly, Hadil; Karaoui, Lamis R","year":2025,"journal":"The Annals of pharmacotherapy, 59(2), 148-161","doi":"10.1177/10600280241253273","pmid":"38767282","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10083","title":"Barriers and Strategies for Oral Peptide and Protein Therapeutics Delivery: Update on Clinical Advances.","authors":"Baral, Kshitis Chandra; Choi, Ki Young","year":2025,"journal":"Pharmaceutics, 17(4)","doi":"10.3390/pharmaceutics17040397","pmid":"40284395","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10084","title":"Nutrition and Physical Activity in Optimizing Weight Loss and Lean Mass Preservation in the Incretin-Based Medications Era: A Narrative Review.","authors":"Barana, Luisa; De Fano, Michelantonio; Cavallo, Massimiliano; Manco, Marcello; Prete, Deborah; Fanelli, Carmine Giuseppe; Porcellati, Francesca; Pippi, Roberto","year":2025,"journal":"Nutrients, 18(1)","doi":"10.3390/nu18010131","pmid":"41515247","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10085","title":"Plasma levels of biomarkers associated with vasodilation and neuroinflammation in pediatric patients with head trauma and their relationship with clinical characteristics of patients.","authors":"Baranoglu Kilinc, Yasemin; Dagistan, Yasar; Kilinc, Erkan","year":2025,"journal":"Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery, 41(1), 224","doi":"10.1007/s00381-025-06883-5","pmid":"40608131","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10086","title":"GLP-1 Receptor Signaling and Oral Dysfunction: A Narrative Review on the Mechanistic Basis of Semaglutide-Related Oral Adverse Effects.","authors":"Barać, Milena; Roganović, Jelena","year":2025,"journal":"Biology, 14(12)","doi":"10.3390/biology14121650","pmid":"41463424","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10087","title":"A 24-week prospective, multicenter, real-world study on eptinezumab's effectiveness and safety in migraine prevention (EMBRACE II).","authors":"Barbanti, Piero; Aurilia, Cinzia; Egeo, Gabriella; Doretti, Alberto; d'Onofrio, Florindo; Scatena, Paola; Rinalduzzi, Steno; Vinciguerra, Luisa; Sansone, Mattia; Vecchio, Rosario; Drago, Valeria; Viticchi, Giovanna; Bartolini, Marco; Ranieri, Angelo; Bandettini di Poggio, Monica; Baldisseri, Francesco; Mascarella, Davide; Brusaferri, Fabio; Caputi, Luigi; Messina, Stefano; Autunno, Massimo; Valenza, Alessandro; Orlando, Bianca; Distefano, Marisa; Borrello, Laura; Pistoia, Francesca; Camarda, Cecilia; Saporito, Gennaro; Querzola, Giacomo; Torelli, Paola; Salerno, Antonio; Gragnani, Francesca; Petolicchio, Barbara; Carnevale, Antonio; Messina, Roberta; Filippi, Massimo; Tavani, Sofia; Fiorentini, Giulia; Bonassi, Stefano; Cevoli, Sabina; Mannocci, Alice","year":2025,"journal":"Journal of neurology, 272(6), 382","doi":"10.1007/s00415-025-13095-z","pmid":"40332560","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10088","title":"GIANT: a prospective, multicenter, real-world study on the effectiveness, safety, and tolerability of atogepant in migraine patients with multiple therapeutic failures.","authors":"Barbanti, Piero; Egeo, Gabriella; Pistoia, Francesca; Aurilia, Cinzia; Scatena, Paola; Rinalduzzi, Steno; Strumia, Silvia; Salerno, Antonio; Frediani, Fabio; Galli, Andrea; Autunno, Massimo; Di Clemente, Laura; Zucco, Maurizio; Albanese, Maria; Bono, Francesco; Bruno, Pietrantonio; Borrello, Laura; Messina, Stefano; Doretti, Alberto; Ranieri, Angelo; Camarda, Cecilia; Vecchio, Rosario; Drago, Valeria; Fiorentini, Giulia; Tomino, Carlo; Bonassi, Stefano; Torelli, Paola; Mannocci, Alice","year":2025,"journal":"The journal of headache and pain, 26(1), 122","doi":"10.1186/s10194-025-02068-2","pmid":"40389834","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10089","title":"Super- and absolute responders to anti-cgrp monoclonal antibodies in migraine: A one-year multicenter, prospective, observational study.","authors":"Barbanti, Piero; Aurilia, Cinzia; Fiorentini, Giulia; Egeo, Gabriella; Mascarella, Davide; Proietti, Stefania; Messina, Roberta; Filippi, Massimo; Bonassi, Stefano; Torelli, Paola; Cevoli, Sabina","year":2025,"journal":"Journal of neurology, 272(10), 683","doi":"10.1007/s00415-025-13419-z","pmid":"41065876","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10090","title":"Perioperative bronchoaspiration in a semaglutide user on a residue-free diet: a case report and insights from a complication.","authors":"Barbosa Santos, Leonardo; Muniz da Silva, Leopoldo; Silveira, Saullo Q; Nersessian, Rafael S F; Matheus, Giulia D; Mizubuti, Glenio B; Edson Vieira, Joaquim","year":2025,"journal":"Perioperative medicine (London, England), 14(1), 115","doi":"10.1186/s13741-025-00603-y","pmid":"41137050","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Despite discontinuing semaglutide six days before surgery, adhering to a 24-hour residue-free diet, and completing a 12-hour fast — exceeding standard preoperative fasting guidelines — the patient experienced large-volume regurgitation during anesthesia induction requiring urgent airway management. Postoperative chest CT confirmed aspiration-related inflammatory changes in the lungs.\n\nA critical contributing factor was the patient's failure to disclose semaglutide use during preoperative evaluation because she didn't consider it a medication. A planned preoperative gastric ultrasound was also omitted due to a protocol breach, which would have revealed retained gastric contents.","whyItMatters":"With tens of millions of people now using semaglutide and similar GLP-1 drugs, the risk of perioperative aspiration is a growing patient safety concern. This case shows that even measures stricter than current guidelines — including a residue-free diet and extended fasting — may not prevent the risk. It has direct implications for anesthesiologists, surgeons, and patients regarding preoperative protocols for GLP-1 users.","specificNumbers":"","methodology":"This is a single case report describing the clinical course of a 61-year-old female with obesity and COPD who experienced perioperative aspiration during elective coronary angiography. The report details the preoperative preparation, the aspiration event, imaging findings, and recovery, along with analysis of contributing factors.","limitations":"As a single case report, this cannot establish how common aspiration events are in semaglutide users despite extended fasting. Individual factors — the patient's obesity, COPD, and the specific procedure — may have contributed to the severity. The omission of preoperative gastric ultrasound (a protocol breach) means it's unknown whether this safety measure would have prevented the complication. The exact residual gastric volume was not quantified."},{"rthcId":"RPEP-10091","title":"Does Sex Affect the Efficacy, Safety, and Quality of Life Outcomes for Patients Using Angiotensin Receptor Neprilysin Inhibitor, Soluble Guanylate Cyclase Stimulators, and Cardiac Myosin Activators in Heart Failure? A Systematic Review.","authors":"Barbosa, Amanda Veiga; Araújo Silva, Lucas Caetano; Rotta, Inajara; Aguiar, Patricia Melo","year":2025,"journal":"Heart, lung & circulation, 34(11), 1169-1178","doi":"10.1016/j.hlc.2025.04.082","pmid":"41062399","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10092","title":"Mood Disorders, Metabolic Bariatric Surgery, and Weight Loss Pharmacotherapy: a Research Update.","authors":"Barbuti, Margherita; Weiss, Francesco; Perugi, Giulio","year":2025,"journal":"Current obesity reports, 14(1), 82","doi":"10.1007/s13679-025-00674-4","pmid":"41313528","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies a dual-edged relationship between weight-loss interventions and psychiatric outcomes:\n\nBenefits: Both bariatric surgery and incretin-based therapies (GLP-1 receptor agonists) can improve metabolic health and, in some cases, mental well-being — likely through reduced inflammation, improved self-image, and metabolic normalization.\n\nRisks: Post-bariatric surgery, studies show increased risks of mood episodes, self-harm behaviors, and altered metabolism of psychiatric medications (due to changes in gut absorption). For GLP-1 receptor agonists specifically, concerns have emerged about potential links to depression and suicidality, though the evidence is still being evaluated.\n\nThe authors recommend thorough psychiatric assessment before initiating any weight-loss intervention and long-term psychiatric monitoring after treatment.","whyItMatters":"As GLP-1 drugs are prescribed to millions of people for weight loss — many of whom have coexisting mood disorders — understanding the psychiatric implications is critical. The potential link between GLP-1 drugs and suicidality has generated regulatory attention (FDA, EMA reviews). This review provides the most comprehensive assessment of both the benefits and risks, advocating for a multidisciplinary approach that doesn't separate metabolic treatment from psychiatric care.","specificNumbers":"","methodology":"Narrative research review examining the published literature on the bidirectional relationship between mood disorders and obesity, with specific focus on psychiatric outcomes following metabolic bariatric surgery and weight-loss pharmacotherapy (particularly GLP-1 receptor agonists). The review synthesizes findings from observational studies, pharmacovigilance reports, and clinical trial data.","limitations":"As a narrative review, this paper synthesizes but does not systematically quantify the evidence. The GLP-1/suicidality signal is based on pharmacovigilance reports and observational data, not controlled trials designed to assess psychiatric outcomes. The psychiatric risks of bariatric surgery may be confounded by pre-existing conditions, surgical stress, and lifestyle changes. The review does not quantify risk magnitudes or provide pooled estimates."},{"rthcId":"RPEP-10093","title":"An effort to enhance the clinical translatability of caprate-based tablet formulations in gastric peptide delivery.","authors":"Bardonnet, Pierre-Louis; Niu, Zhigao; Pessi, Jenni; Kazakou, Maria; Raptis, Konstantinos; McCabe, Reece; Toftlev, Anders; Rebollo, René; Wang, Zhuoran; Fan, Li; Mortensen, Nicolai Rytter; Bardtrum, Lars; Andersson, Vincent; Wahlund, Per-Olof; Norrman, Mathias; Benie, Andrew James; Wu, Jian Xiong; Sauter, Max; Zara, Damiano La; Christophersen, Philip; Sassene, Philip Jonas","year":2025,"journal":"Drug delivery and translational research","doi":"10.1007/s13346-025-01978-7","pmid":"40988000","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10094","title":"Efficacy of incretin-based therapies in obesity-related obstructive sleep apnea: a systematic review and meta-analysis of randomized controlled trials.","authors":"Bardóczi, Anna; Matics, Zsombor Zoltán; Turan, Caner; Szabó, Bence; Molnár, Zsolt; Hegyi, Péter; Müller, Veronika; Horváth, Gábor","year":2025,"journal":"Sleep medicine reviews, 82, 102119","doi":"10.1016/j.smrv.2025.102119","pmid":"40633481","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10095","title":"A therapeutic peptide vaccine for fibrolamellar hepatocellular carcinoma: a phase 1 trial.","authors":"Baretti, Marina; Kirk, Allison M; Ladle, Brian H; Kamdar, Zeal; Bendinelli, Kayla J; Ho, Won Jin; Adhikari, Samir; Clark, Nicholas A; Sundararaman, Balaji; Wang, Hao; Kung, Heng-Chung; Hernandez, Jeric; Qi, Hanfei; Shin, Sarah M; Hernandez, Alexei; Nakazawa, Mari; Schattgen, Stefan A; Crawford, Jeremy Chase; Furth, Mark; Anders, Robert A; Thoburn, Chris; Zaidi, Neeha; Huff, Amanda L; Nauroth, Julie; Jaffee, Elizabeth; Pogorelyy, Mikhail V; Thomas, Paul G; Yarchoan, Mark","year":2025,"journal":"Nature medicine, 31(12), 4246-4255","doi":"10.1038/s41591-025-03995-y","pmid":"41286513","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10096","title":"Antibiofilm, regenerative and bone homeostasis potential of the synergistic association of synoeca-MP peptide with chlorhexidine in oral cavity opportunistic infections.","authors":"Barin, Ingrid Aquino Reichert; da Silva, Johnny Carvalho; Ramos, Raquel Figuerêdo; Lima, Stella Maris de Freitas; Cantuária, Ana Paula de Castro; Silva, Poliana Amanda Oliveira; Dantas, Elaine Maria Guará Lôbo; Martins, Danilo César Mota; de Oliveira, Nelson Gomes; Martínez, Osmel Fleitas; de Almeida, Jeeser Alves; Ramada, Marcelo Henrique Soller; Franco, Octávio Luiz; Rezende, Taia Maria Berto","year":2025,"journal":"Archives of oral biology, 172, 106177","doi":"10.1016/j.archoralbio.2025.106177","pmid":"39889438","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Synoeca-MP and chlorhexidine showed synergistic antimicrobial and antibiofilm activity against oral pathogens at reduced concentrations. The synergistic combination was stable in healthy human saliva but degraded as periodontal disease severity increased. At low synergistic doses, the combination was non-cytotoxic, promoted periodontal ligament cell proliferation and migration, inhibited osteoclastogenesis (bone resorption), and increased mineralized matrix formation in both ligament cells and SaOs-2 osteoblast-like cells.","whyItMatters":"Periodontal disease is among the most common infections worldwide and leads to tooth loss through bone destruction. Current treatments have limited ability to simultaneously fight infection AND promote tissue regeneration. This peptide-chlorhexidine combination addresses both problems at once — killing bacteria while actively promoting bone healing and tissue repair. This dual action could significantly improve outcomes for periodontal therapy.","specificNumbers":"","methodology":"In vitro study determining minimum inhibitory and bactericidal concentrations, antibiofilm concentrations, and synergy between synoeca-MP and chlorhexidine. Saliva stability was tested in samples from patients with varying degrees of periodontal disease. Biocompatibility was assessed via MTT and hemolytic assays. Regenerative potential was evaluated through periodontal ligament cell proliferation/migration assays, osteoclastogenesis assays, alkaline phosphatase determination, and mineralized matrix formation assays using SaOs-2 cells.","limitations":"This is entirely an in vitro study — results need validation in animal models and clinical trials. The degradation of the combination in diseased saliva is concerning, as that's precisely the environment where treatment is needed most. The specific oral pathogens tested were not named in the abstract. Long-term effects on oral microbiome balance were not assessed. Manufacturing and delivery challenges for a clinical product were not addressed."},{"rthcId":"RPEP-10097","title":"Liraglutide modulates cyclooxygenase and α7 acetylcholine receptors: in vitro and in silico insights into its anti-inflammatory role in LPS-induced inflammation in RAW 264.7 macrophages.","authors":"Baris, Elif; Portakal, Huseyin Saygin; Aslan, Arda; Firtina Karagonlar, Zeynep; Tosun, Metiner","year":2025,"journal":"Naunyn-Schmiedeberg's archives of pharmacology, 398(11), 16229-16239","doi":"10.1007/s00210-025-04225-5","pmid":"40448826","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10098","title":"Calcitonin gene-related peptide-targeted therapies for migraine.","authors":"Barnes, Stephanie; Aldous, Lucie; Jenkins, Bronwyn","year":2025,"journal":"Australian prescriber, 48(2), 40-46","doi":"10.18773/austprescr.2025.017","pmid":"40343132","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10099","title":"Semaglutide therapy and iatrogenic thyrotoxicosis.","authors":"Barnett, Maxim John Levy; Eidbo, Sarah; Rivadeneira, Ana","year":2025,"journal":"Endocrinology, diabetes & metabolism case reports, 2025(3)","doi":"10.1530/EDM-25-0065","pmid":"40638337","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10100","title":"A Multidisciplinary Perspective on Semaglutide Treatment and Medical Nutrition Therapy in Obesity Management.","authors":"Barrea, Luigi; Annunziata, Giuseppe; Verde, Ludovica; Galasso, Martina; Savastano, Silvia; Colao, Annamaria; Muscogiuri, Giovanna","year":2025,"journal":"Current obesity reports, 14(1), 73","doi":"10.1007/s13679-025-00667-3","pmid":"41129057","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10101","title":"Long-Term Efficacy and Safety of Nutritional and Pharmacological Strategies for Obesity.","authors":"Barrea, Luigi; Boschetti, Mara; Gangitano, Elena; Guglielmi, Valeria; Verde, Ludovica; Muscogiuri, Giovanna","year":2025,"journal":"Current obesity reports, 14(1), 1","doi":"10.1007/s13679-024-00602-y","pmid":"39753703","tags":[],"studyType":"review","evidenceStrength":"moderate","keyFinding":"This review compares long-term obesity management strategies including the Mediterranean diet (MedDiet), very low-energy ketogenic therapy (VLEKT), naltrexone/bupropion, and the GLP-1 receptor agonist peptide liraglutide. The MedDiet offers sustainable cardiovascular benefits with moderate weight loss. VLEKT produces rapid weight loss but has sustainability concerns. Both liraglutide and naltrexone/bupropion promote significant weight loss and improve metabolic markers, but long-term adherence and side effects remain open questions for both pharmacological approaches.","whyItMatters":"Obesity is a chronic disease requiring sustained treatment. This review places GLP-1 receptor agonists like liraglutide alongside dietary interventions in a comparative framework, highlighting that while peptide drugs produce significant short-term weight loss, the Mediterranean diet may be more sustainable long-term. Understanding how to combine these approaches optimally is critical for lasting obesity management.","specificNumbers":"","methodology":"Narrative review examining published evidence on long-term efficacy and safety of four obesity management strategies: Mediterranean diet, very low-energy ketogenic therapy, naltrexone/bupropion, and liraglutide. The review evaluates weight loss outcomes, metabolic improvements, cardiovascular benefits, adherence, and safety profiles.","limitations":"This is a narrative review, not a systematic review or meta-analysis. It focuses on liraglutide rather than newer GLP-1 RAs like semaglutide or tirzepatide, which have shown greater weight loss efficacy. Direct head-to-head comparisons between dietary and pharmacological strategies are limited in the literature. The review acknowledges that long-term data beyond 1-2 years remain sparse for most interventions."},{"rthcId":"RPEP-10102","title":"A Managed Access Protocol for Liraglutide for Weight Management: A Retrospective, Observational Study in Ireland.","authors":"Barrett, Rosealeen; Smith, Amelia; Gorry, Claire; Doran, Stephen; Barry, Michael; McCullagh, Laura","year":2025,"journal":"Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research, 28(6), 844-851","doi":"10.1016/j.jval.2025.03.017","pmid":"40246067","tags":["liraglutide","glp-1","weight-management"],"studyType":"observational-retrospective","evidenceStrength":"moderate","keyFinding":"Ireland's Managed Access Protocol (MAP) for liraglutide (Saxenda) approved 52.2% of the 7,927 physician applications submitted in its first year. By targeting reimbursement to the patient subpopulation most likely to benefit cost-effectively, the MAP contained spending to approximately €3.1 million in 2023 — compared to an estimated €5.5 million if all applications had been approved.\n\nApproved patients differed from denied patients in key characteristics including age, HbA1c, and BMI, suggesting the MAP successfully selected a higher-risk subgroup where the drug offers the most value.","whyItMatters":"GLP-1 drugs for weight loss are expensive, and healthcare systems worldwide are struggling with how to pay for them. Ireland's MAP offers a real-world model for balancing patient access with fiscal sustainability — approving the drug for roughly half of applicants based on cost-effectiveness criteria rather than blanket coverage or blanket denial.","specificNumbers":"7,927 applications · 52.2% approved · €3.1M actual spend · €5.5M projected without MAP · Year 1 data · Saxenda (liraglutide 3.0 mg)","methodology":"Retrospective observational study analyzing two data sources: Ireland's national anonymized MAP database of liraglutide applications and the national reimbursed pharmacy claims database. Compared characteristics of approved vs. denied applications and actual vs. projected expenditure in the first year of the MAP.","limitations":"Retrospective and observational design. Single-country study specific to Ireland's healthcare system, which may not generalize to other reimbursement models. Only captures the first year of the MAP. Does not directly measure clinical outcomes of patients who received vs. were denied liraglutide. Cost-effectiveness assessments rely on modeled rather than observed outcomes."},{"rthcId":"RPEP-10103","title":"Heart Failure With Preserved Ejection Fraction.","authors":"Barzin, Amir; Barnhouse, Kathleen K; Kane, Shawn F","year":2025,"journal":"American family physician, 112(4), 435-440","doi":null,"pmid":"41118188","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10104","title":"Semaglutide Modulates Proinflammatory Epicardial Adipogenesis With Paracrine Effects on hiPSC-Atrial Cardiomyocytes.","authors":"Basdas, Rumeysa; Martínez-Cereijo, José Manuel; Fernández, Ángel L; Reija, Laura; Cabaleiro, Alba; Bravo, Susana Belén; González-Juanatey, José R; Eiras, Sonia","year":2025,"journal":"JACC. Basic to translational science, 10(9), 101277","doi":"10.1016/j.jacbts.2025.03.009","pmid":"40471762","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10105","title":"External control arm with real world data to assess the effect of semaglutide on chronic kidney disease risk among patients with type 2 diabetes.","authors":"Baser, Onur; Lu, Yuanqing","year":2025,"journal":"Expert opinion on pharmacotherapy, 26(10), 1237-1243","doi":"10.1080/14656566.2025.2518329","pmid":"40489337","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10106","title":"Diagnosing Heart Failure with Preserved Ejection Fraction in Obese Patients.","authors":"Basha, Marino; Stavropoulou, Evdoxia; Nikolaidou, Anastasia; Dividis, Georgios; Peteinidou, Emmanouela; Tsioufis, Panagiotis; Kamperidis, Nikolaos; Dimitriadis, Kyriakos; Karamitsos, Theodoros; Giannakoulas, George; Tsioufis, Konstantinos; Ziakas, Antonios; Kamperidis, Vasileios","year":2025,"journal":"Journal of clinical medicine, 14(6)","doi":"10.3390/jcm14061980","pmid":"40142788","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10107","title":"Effect of Incretin-Based Therapies on Blood Pressure: A Systematic Review and Meta-Analysis.","authors":"Basile, Christian; Merolla, Aurora; Mancusi, Costantino; De Luca, Carmine; Fucile, Ilaria; Canonico, Mario Enrico; Giugliano, Giuseppe; Orso, Francesco; Morisco, Carmine; Esposito, Giovanni","year":2025,"journal":"European journal of preventive cardiology","doi":"10.1093/eurjpc/zwaf560","pmid":"40899050","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10108","title":"Empagliflozin and hydralazine-isosorbide dinitrate combination therapy improves outcomes in Black patients with heart failure.","authors":"Baskaran, Padmamalini; Aldhaeefi, Mohammed; Asaadi, Anahita; Jones, Morgan; King, Emmanuel; Rungkitwattanakul, Dhakrit; Wingate, La'Marcus","year":2025,"journal":"International journal of clinical pharmacology and therapeutics, 63(11), 553-556","doi":"10.5414/CP204854","pmid":"40888214","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10109","title":"Effects of 6-month treatment with the GLP-1 receptor agonist liraglutide on 24-hour energy metabolism and body composition in adults with obesity.","authors":"Basolo, Alessio; Paolucci, Giordano; Piaggi, Paolo; Angeli, Valentina; Bechi Genzano, Susanna; Fierabracci, Paola; Vignali, Edda; Bologna, Chiara; Salvetti, Guido; Chiovato, Luca; Natali, Andrea; Krakoff, Jonathan; Landi, Alberto; Santini, Ferruccio","year":2025,"journal":"Journal of endocrinological investigation, 48(11), 2735-2745","doi":"10.1007/s40618-025-02717-y","pmid":"41060519","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"After 6 months of liraglutide treatment in 11 obese adults:\n\nBody composition changes:\n- Total weight loss: -10.5 kg (P < 0.001)\n- Fat mass loss: -8.7 kg (P < 0.001), predominantly from trunk: -5.1 kg (P < 0.001)\n- Lean tissue loss: only -1.7 kg (P = 0.02) — largely preserved\n\nMetabolic changes (24-hour whole-room calorimetry):\n- 24h energy expenditure: no significant change (metabolic rate maintained)\n- 24h sleeping metabolic rate: no significant change\n- Fat oxidation: +352 kcal/day (P = 0.03)\n- Carbohydrate oxidation: -422 kcal/day (P = 0.003)\n- Protein oxidation: stable\n\nThe preservation of energy expenditure despite weight loss is notable because metabolic slowing typically accompanies weight loss and drives regain.","whyItMatters":"One of the biggest concerns about weight loss drugs is that they might cause 'bad' weight loss — losing muscle along with fat, or slowing metabolism so weight regain is inevitable. This study provides reassuring metabolic data: liraglutide's weight loss was 83% fat (especially dangerous trunk fat), muscle was largely preserved, and total energy expenditure didn't drop. The shift toward fat burning suggests the body is efficiently using fat stores rather than just reducing metabolism. These findings help explain the quality of weight loss with GLP-1 drugs.","specificNumbers":"","methodology":"Prospective single-arm study at the Obesity and Lipodystrophy Center, University Hospital of Pisa. 11 patients with obesity (8 female, mean age 49, mean weight 103 kg) were treated with liraglutide at clinically titrated doses for 6 months. 24-hour energy expenditure and substrate oxidation were measured via whole-room indirect calorimetry (metabolic chamber) at baseline and 6 months. Body composition was assessed by DXA (dual-energy X-ray absorptiometry) at both timepoints.","limitations":"Very small sample size (n=11) significantly limits generalizability and statistical power. No control group — all changes attributed to liraglutide could partially reflect diet/lifestyle changes. Only liraglutide was tested; results may not apply to other GLP-1RAs like semaglutide. The 6-month duration captures early weight loss but not long-term metabolic adaptation. The 1.7 kg lean tissue loss, while modest, warrants monitoring in longer-term treatment. The study population was predominantly female (8/11)."},{"rthcId":"RPEP-10110","title":"Integrative bioinformatic analysis of prognostic biomarkers in heart failure: Insights from clinical trials.","authors":"Bastos, José Mesquita; Scala, Noemi; Perpétuo, Luís; Mele, Bruno Hay; Vitorino, Rui","year":2025,"journal":"European journal of clinical investigation, 55(4), e70010","doi":"10.1111/eci.70010","pmid":"39957002","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10111","title":"Recombinant expression and functional characterization of defensin-like peptide TEWP and its analogs in Pichia pastoris.","authors":"Batman, Saime Gülsüm; Kesmen, Zülal","year":2025,"journal":"World journal of microbiology & biotechnology, 41(10), 392","doi":"10.1007/s11274-025-04618-x","pmid":"41099884","tags":[],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Researchers engineered three modified versions of TEWP, a defensin-like antimicrobial peptide originally found in sea turtle eggs. Reversing the peptide sequence and attaching a cell-penetrating peptide (CPP) doubled the antimicrobial activity while significantly reducing toxicity to human red blood cells. All variants were effective against 19 microbial strains, with the strongest activity against Listeria monocytogenes at concentrations of just 2–4 μg/mL.\n\nThe peptides were successfully produced at scale using engineered Pichia pastoris yeast and showed resistance to heat, protease degradation, and high salt concentrations — properties critical for real-world pharmaceutical use.","whyItMatters":"Antibiotic resistance is a growing global crisis, and antimicrobial peptides are one of the most promising alternatives to conventional antibiotics. This study tackles two key challenges: making these peptides more potent and less toxic through rational design, and producing them affordably at scale using yeast expression systems. The stability of these engineered peptides under harsh conditions makes them realistic candidates for pharmaceutical development.","specificNumbers":"MIC: 2–4 μg/mL vs L. monocytogenes · 2-fold increase in antimicrobial activity (reversed + CPP variant) · Net charge +12 · 19 microbial strains tested · 96 h methanol induction · Produced in P. pastoris GS115","methodology":"The researchers designed three TEWP analogs using different strategies: amino acid substitution (MTEWP), sequence reversal (RMTEWP), and conjugation with a cell-penetrating peptide ((RW)4RMTEWP). Each was produced recombinantly in Pichia pastoris yeast with a 6xHis tag. Antimicrobial activity was tested against 19 microbial strains, hemolytic activity was assessed, and stability was evaluated under heat treatment, protease exposure, and high salt conditions.","limitations":"This is an in vitro study only — no animal or human testing was performed. Activity against 19 lab strains may not reflect performance against clinical drug-resistant isolates. The production yields in Pichia pastoris were not quantified in the abstract. Long-term stability and in vivo pharmacokinetics remain unknown."},{"rthcId":"RPEP-10112","title":"Glucagon-like peptide-1 receptor agonists and the endothelium: molecular and clinical insights into cardiovascular protection.","authors":"Battistoni, Allegra; Piras, Linda; Tartaglia, Nicola; Carrano, Francesco Maria; De Vitis, Claudia; Barbato, Emanuele","year":2025,"journal":"Frontiers in medicine, 12, 1669685","doi":"10.3389/fmed.2025.1669685","pmid":"40995089","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10113","title":"Interconnected pathways and emerging therapies in chronic kidney disease and heart failure: A comprehensive review.","authors":"Bauersachs, Johann; Kato, Eri Toda; Rangaswami, Janani","year":2025,"journal":"ESC heart failure, 12(5), 3226-3249","doi":"10.1002/ehf2.15345","pmid":"40533425","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10114","title":"Cost-Consequence Analysis of Semaglutide vs. Liraglutide for Managing Obese Prediabetic and Diabetic Patients in Saudi Arabia: A Single-Center Study.","authors":"Bawazeer, Najla; Bin Ganzal, Seham; Al-Hasinah, Huda F; Alruthia, Yazed","year":2025,"journal":"Healthcare (Basel, Switzerland), 13(14)","doi":"10.3390/healthcare13141755","pmid":"40724780","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10115","title":"Glucagon-Like Peptide 1 Receptor Agonists and Risk of Thyroid Cancer: An International Multisite Cohort Study.","authors":"Baxter, Sarah M; Lund, Lars Christian; Andersen, Jacob H; Brix, Thomas H; Hegedüs, Laszlo; Hsieh, Miyuki Hsing-Chun; Su, Chris Tzu-Ting; Cheng, Michael Chun-Yuan; Chang, Zoe Chi-Jui; Lai, Edward Chia-Cheng; Hussain, Swaleh; Chu, Cherry; Gomes, Tara; Antoniou, Tony; Eskander, Antoine; Bouck, Zachary; Tadrous, Mina; Bea, Sungho; Choi, Eun-Young; Shin, Ju-Young; Modig, Karin; Talbäck, Mats; Ljung, Rickard; Gulseth, Hanne Løvdal; Karlstad, Øystein; Hicks, Blánaid; Pottegård, Anton","year":2025,"journal":"Thyroid : official journal of the American Thyroid Association, 35(1), 69-78","doi":"10.1089/thy.2024.0387","pmid":"39772758","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10116","title":"Glucagon-like peptide 1 receptor agonists and the clinical outcomes of inflammatory bowel disease: a systematic review and meta-analysis.","authors":"Bayoumy, Ahmed B; Clarke, Lindsay M; Deepak, Parakkal; Desai, Aakash; Sehgal, Priya; Gorelik, Uri; Bar-Yoseph, Haggai; Villumsen, Marie; Mulder, Chris J J; Stenvers, Dirk J; Tushuizen, Maarten E; de Boer, Nanne K H","year":2025,"journal":"Journal of Crohn's & colitis, 19(10)","doi":"10.1093/ecco-jcc/jjaf181","pmid":"41071055","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10117","title":"Blood pressure changes during smoking cessation in a randomized, double-blind, placebo-controlled trial of dulaglutide treatment.","authors":"Beck, Julia; Hasenböhler, Flavia; Werlen, Laura; Lengsfeld, Sophia; Meienberg, Andrea; Bathelt, Cemile; Vogt, Deborah; Christ-Crain, Mirjam; Burkard, Thilo; Winzeler, Bettina","year":2025,"journal":"European journal of preventive cardiology, 32(14), 1394-1402","doi":"10.1093/eurjpc/zwaf055","pmid":"40037282","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10118","title":"Molecular response to the non-lytic peptide bac7 (1-35) triggers disruption of Klebsiella pneumoniae biofilm.","authors":"Beckman I V, Robert L; Martinez, Berta; Santiago, Flor Z; Echeverria, Gabriela N; Pinheiro, Bruno V; D T Torres, Marcelo; Suits, Logan; Garcia, Shantal; Wantuch, Paeton L; de la Fuente-Nunez, Cesar; Eswara, Prahathees; Rosen, David A; Fleeman, Renee M","year":2025,"journal":"PLoS pathogens, 21(12), e1013437","doi":"10.1371/journal.ppat.1013437","pmid":"41325418","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10119","title":"A randomized phase I study of BI 1820237, a novel neuropeptide Y receptor type 2 agonist, alone or in combination with low-dose liraglutide in otherwise healthy men with overweight or obesity.","authors":"Beetz, Nadine; Kalsch, Brigitte; Forst, Thomas; Schmid, Bernhard; Schultz, Armin; Hennige, Anita M","year":2025,"journal":"Diabetes, obesity & metabolism, 27(1), 71-80","doi":"10.1111/dom.15984","pmid":"39373311","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10120","title":"Enzyme-free biochemical production of seamlessly N-to-C cyclized peptides from natural or recombinant proteins.","authors":"Behboodian, Ali; Serebryany, Eugene","year":2025,"journal":"Methods in enzymology, 723, 427-453","doi":"10.1016/bs.mie.2025.08.010","pmid":"41266038","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10121","title":"Enzyme-free biochemical production of seamlessly N-to-C cyclized peptides from natural or recombinant proteins.","authors":"Behboodian, Ali; Serebryany, Eugene","year":2025,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2025.07.31.667801","pmid":"40766682","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The researchers demonstrated enzyme-free biochemical cyclization of peptides under mild aqueous conditions using a single, readily available chemical reagent:\n\n- Successfully produced a 17-mer cyclic peptide from wild-type human eye lens γ-crystallin protein\n- Produced a set of 10-residue cyclic peptides from recombinantly expressed polypeptide precursors\n- The method works without disulfides, using only canonical amino acids\n- Products were identified via complex mass spectrometry fragmentation patterns\n- Linear and cyclic peptide forms were chromatographically separated\n- The approach works with both natural protein sources and recombinantly expressed precursors","whyItMatters":"Cyclic peptides are among the most promising classes of peptide drugs because their ring structure makes them more stable and resistant to degradation than linear peptides. However, the gold standard production method (solid-phase synthesis) is expensive, limiting their use to high-value pharmaceutical applications. This enzyme-free method could make cyclic peptides accessible for a much wider range of uses, potentially reducing drug costs and enabling new applications.","specificNumbers":"","methodology":"The researchers developed a chemical cyclization protocol using mild aqueous conditions and a single reagent. They tested the method on natural protein (human γ-crystallin) and recombinant polypeptide precursors. They systematically investigated how reaction conditions and amino acid sequence changes affect cyclization efficiency. Products were verified using mass spectrometry fragmentation analysis and chromatographic separation of linear from cyclic forms.","limitations":"This is a preprint (bioRxiv), meaning it has not yet undergone peer review. The method has been demonstrated at laboratory scale but scalability to industrial production is unproven. The efficiency and yield of the cyclization reaction across diverse peptide sequences needs broader characterization. The study does not assess whether the cyclic peptides produced retain the biological activity needed for specific therapeutic applications."},{"rthcId":"RPEP-10122","title":"Blood pressure effects of SGLT2 inhibitors and GLP-1 receptor agonists: Mechanisms, trial evidence and Real-world data.","authors":"Belančić, Andrej; Sener, Yusuf Ziya; Vučković, Marijana; Blais, Joseph Edgar; Fajkić, Almir; Sher, Emina; Radić, Mislav; Radić, Josipa","year":2025,"journal":"British journal of clinical pharmacology","doi":"10.1002/bcp.70378","pmid":"41344902","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10123","title":"Evaluation of a Point-of-Care N-Terminal Pro-Brain Natriuretic Peptide Assay for Heart Failure Management.","authors":"Belik, Florian; Benamour, Meryem; Laffalize, Antoine; Lavalleye, Thibault; Van Belle, Louisa; Pouleur, Anne-Catherine; Gruson, Damien","year":2025,"journal":"Cardiology research, 16(5), 447-452","doi":"10.14740/cr2117","pmid":"41170016","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10124","title":"In adults with obesity and knee OA, adding weekly semaglutide to diet and activity counseling reduced weight and knee pain at 68 wk.","authors":"Bell, David S H","year":2025,"journal":"Annals of internal medicine, 178(2), JC20","doi":"10.7326/ANNALS-24-03988-JC","pmid":"39899871","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10125","title":"Probing Guanidino Pendant or Bridged Groups in Cyclic Antimicrobial Peptides Derived from Temporin L: A Strategy to Improve Efficacy against Gram-Negative Bacteria.","authors":"Bellavita, Rosa; Boccino, Ida; Loffredo, Maria Rosa; Palladino, Sara; Cappiello, Floriana; Vetrano, Carlo; Tortellini, Eeva; Mazzarella, Vincenzo; Di Maro, Salvatore; Galdiero, Stefania; Casciaro, Bruno; Grieco, Paolo; Mangoni, Maria Luisa; Merlino, Francesco","year":2025,"journal":"Journal of medicinal chemistry, 68(23), 25038-25060","doi":"10.1021/acs.jmedchem.5c01984","pmid":"41326206","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10126","title":"Synergistic Cancer Metabolic Therapy via Co-Delivery of 3-Bromopyruvate and Temozolomide with a Supramolecular Shuttle.","authors":"Bellavita, Rosa; Prisco, Marina; Palladino, Sara; Barra, Teresa; Donadio, Federica; Esposito, Emanuela; Esposito, Rodolfo; Panico, Giuliana; Pisano, Jessica; Venditti, Paola; Valiante, Salvatore; Falanga, Annarita; D'Errico, Gerardino; Lombardi, Assunta; Galdiero, Stefania","year":2025,"journal":"ACS applied materials & interfaces, 17(44), 60342-60360","doi":"10.1021/acsami.5c17607","pmid":"41124053","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The peptide nanofiber successfully co-delivered 3-bromopyruvate (a glycolysis inhibitor) and temozolomide (a standard chemotherapy drug) to glioblastoma cells. The system used an MMP-9-responsive linker for controlled, on-demand drug release at the tumor site. The nanofiber was functionalized with the falGea peptide for EGFRvIII-targeted delivery and gH625 for blood-brain barrier penetration.\n\nIn both 2D and 3D U-87 MG glioblastoma cell cultures, the combination therapy delivered via the nanofiber platform demonstrated therapeutic efficacy. Testing with a dynamic 3D in vitro blood-brain barrier model confirmed that the gH625 peptide enhanced transport across the BBB.","whyItMatters":"Glioblastoma is one of the most aggressive and difficult-to-treat brain cancers, partly because the blood-brain barrier blocks most drugs from reaching the tumor. This peptide-based delivery system addresses two major challenges at once: getting drugs across the BBB and combining two complementary therapies to attack cancer through different pathways, potentially reducing the doses needed and limiting side effects.","specificNumbers":"","methodology":"The researchers designed a self-assembling peptide nanofiber and characterized its aggregation behavior, structural stability, and shape. They tested its effects on isolated rat brain mitochondria to confirm mitochondrial targeting. Anti-cancer activity was evaluated in U-87 MG glioblastoma cells grown in both traditional flat cultures (2D) and more realistic spheroid cultures (3D). Blood-brain barrier permeability was tested using a dynamic 3D in vitro BBB model.","limitations":"This study was conducted entirely in laboratory settings — using cell cultures and an in vitro BBB model, not living animals or human patients. While the 3D culture and BBB models are more realistic than basic cell tests, they still don't capture the full complexity of a living brain tumor environment. The long-term stability, toxicity profile, and actual in vivo efficacy of the nanofiber system remain to be determined."},{"rthcId":"RPEP-10127","title":"Transport across membrane meets biophysics to unveil the mechanism of action of a novel gH625 analogue.","authors":"Bellavita, Rosa; Pecoraro, Annalisa; Palladino, Sara; Danisi, Camilla; Falanga, Annarita; D'Auria, Gabriella; Falcigno, Lucia; Russo, Giulia; Galdiero, Stefania; Russo, Annapina","year":2025,"journal":"European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 212, 107204","doi":"10.1016/j.ejps.2025.107204","pmid":"40675344","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10128","title":"Neuropeptide Y1 receptor expressing circuit from the central amygdala to lateral hypothalamus modulates binge-like ethanol consumption in a sex-dependent manner.","authors":"Bendrath, Sophie C; Stone, Ashlyn; Dankert, Anne M; Thiele, Todd E","year":2025,"journal":"Alcohol, clinical & experimental research, 49(10), 2146-2162","doi":"10.1111/acer.70151","pmid":"40884023","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10129","title":"GLP1 receptor agonism alters growth and therapeutic response in prostate cancer.","authors":"Bera, Soumen; Gutgesell, Lisa C; Darden, Brynne; Sargis, Robert M; Maienschein-Cline, Mark; Gaber, Charles E; Reizine, Natalie M; Vander Griend, Donald J; Vellky, Jordan E","year":2025,"journal":"Endocrine-related cancer, 32(12)","doi":"10.1530/ERC-25-0185","pmid":"41257454","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10130","title":"Discontinuing glucagon-like peptide-1 receptor agonists and body habitus: A systematic review and meta-analysis.","authors":"Berg, Sara; Stickle, Hannah; Rose, Suzanne J; Nemec, Eric C","year":2025,"journal":"Obesity reviews : an official journal of the International Association for the Study of Obesity, 26(8), e13929","doi":"10.1111/obr.13929","pmid":"40186344","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10131","title":"Long-term safety and tolerability of zavegepant 10-mg nasal spray with concomitant use of anti-calcitonin gene-related peptide monoclonal antibodies or other select preventive migraine medications: Results from a phase 2/3 open-label study.","authors":"Berman, Gary; Mullin, Kathleen; Smith, Timothy; Mosher, Linda; Sweeney, Samantha; Fountaine, Robert J","year":2025,"journal":"Headache, 65(7), 1180-1189","doi":"10.1111/head.14954","pmid":"40391567","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10132","title":"PerseuCPP: a machine learning strategy to predict cell-penetrating peptides and their uptake efficiency.","authors":"Bernardes-Loch, Rayane Monique; de Oliveira Almeida, Gustavo; Brasiliano, Igor Teixeira; Meira, Wagner; Pires, Douglas E V; Baracat-Pereira, Maria Cristina; de Azevedo Silveira, Sabrina","year":2025,"journal":"Bioinformatics advances, 5(1), vbaf213","doi":"10.1093/bioadv/vbaf213","pmid":"41018818","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The CPP prediction model achieved superior performance compared to existing state-of-the-art methods: MCC of 0.854, Recall of 0.860, and AUC of 0.984. The model was trained on a balanced dataset of 967 CPPs and non-CPPs with 10-fold cross-validation and validated on two independent test sets.\n\nThe uptake efficiency predictor — trained on 140 CPPs — achieved competitive results with Recall of 0.761 and AUC of 0.690. The model is interpretable, identifying which physicochemical properties, structural features, and atomic compositions are most important for cell penetration. The tool uses Extremely Randomized Trees as its core algorithm.","whyItMatters":"Drug delivery is one of the biggest challenges in medicine — many promising drugs can't reach their targets inside cells. Cell-penetrating peptides solve this problem but discovering new ones through lab experiments is expensive and slow. PerseuCPP dramatically accelerates this discovery process by computationally screening peptide candidates before any lab work, potentially reducing costs and time in peptide drug delivery development. Its interpretability also teaches researchers what makes a peptide good at entering cells.","specificNumbers":"","methodology":"The researchers built a two-stage machine learning pipeline. Stage one identifies CPPs using an Extremely Randomized Trees classifier trained on 967 peptides (balanced CPPs and non-CPPs) with descriptors capturing physicochemical properties, structural features, and atomic composition. Ten-fold cross-validation was used for training, with two independent datasets for validation. Stage two predicts uptake efficiency using a similar approach trained on 140 peptides. Both stages were benchmarked against existing prediction methods.","limitations":"The uptake efficiency predictor had notably lower performance (AUC 0.690) compared to the CPP identification stage (AUC 0.984), likely due to the small training set of only 140 peptides. Computational predictions need experimental validation — a predicted CPP may not work as expected in actual biological systems. The model was trained on known CPP datasets that may not represent the full diversity of potential cell-penetrating peptides. Performance on novel, structurally unusual peptides is untested."},{"rthcId":"RPEP-10133","title":"Clinical impact of very high-power-short-duration catheters on biomarkers after atrial fibrillation ablation.","authors":"Bernardini, Andrea; Perini, Alessandro Paoletti; Zaccaria, Cristiano Salvatore; Ciliberti, Davide; Signorini, Umberto; Grossi, Francesco; Martone, Raffaele; Fatucchi, Serena; Bertini, Alenja; Arretini, Anna; Innocenti, Lisa; Capecchi, Irene; Padeletti, Margherita; Milli, Massimo; Giomi, Andrea","year":2025,"journal":"Journal of arrhythmia, 41(2), e70060","doi":"10.1002/joa3.70060","pmid":"40207269","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10134","title":"H105A peptide eye drops promote photoreceptor survival in murine and human models of retinal degeneration.","authors":"Bernardo-Colón, Alexandra; Bighinati, Andrea; Parween, Shama; Debnath, Subrata; Piano, Ilaria; Adani, Elisa; Corsi, Francesca; Gargini, Claudia; Vergara, Natalia; Marigo, Valeria; Patricia Becerra, S","year":2025,"journal":"Communications medicine, 5(1), 81","doi":"10.1038/s43856-025-00789-8","pmid":"40118996","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10135","title":"Longitudinal Analysis of Obesity Drug Use and Public Awareness.","authors":"Berning, Philipp; Adhikari, Rishav; Schroer, Adrian E; Jelwan, Yara A; Razavi, Alexander C; Blaha, Michael J; Dzaye, Omar","year":2025,"journal":"JAMA network open, 8(1), e2457232","doi":"10.1001/jamanetworkopen.2024.57232","pmid":"39878977","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10136","title":"Comprehensive Insights into Obesity and Type 2 Diabetes from Protein Network, Canonical Pathway, Phosphorylation and Antimicrobial Peptide Signatures of Human Serum.","authors":"Bertalan, Petra Magdolna; Nokhoijav, Erdenetsetseg; Pap, Ádám; Neagu, George C; Káplár, Miklós; Darula, Zsuzsanna; Kalló, Gergő; Prokai, Laszlo; Csősz, Éva","year":2025,"journal":"Proteomes, 13(4)","doi":"10.3390/proteomes13040067","pmid":"41441338","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10137","title":"Safety, tolerability, and pharmacokinetics of single and multiple ascending doses of zavegepant nasal spray in healthy adults from two phase 1 randomized, placebo-controlled trials.","authors":"Bertz, Richard; Donohue, Mary; Madonia, Jennifer; Bhardwaj, Rajinder; Matschke, Kyle T; Anderson, Matt S; Croop, Robert; Liu, Jing","year":2025,"journal":"Headache, 65(8), 1331-1343","doi":"10.1111/head.15042","pmid":"40859706","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across both studies (144 total participants), zavegepant nasal spray demonstrated rapid absorption with a median time to peak plasma concentration (Tmax) of approximately 0.54 hours (~32 minutes) after a single 10 mg spray. Drug exposure increased proportionally with dose, and there was no evidence of accumulation with repeated once-daily dosing.\n\nSafety was favorable: in the single-dose study, 26% of zavegepant-treated participants reported adverse events versus 17% on placebo. In the multiple-dose study, 75% of zavegepant participants reported adverse events versus 63% on placebo. Most events were mild and self-resolving. No clinically relevant ECG changes or drug-induced liver injury signals were observed at any dose tested (up to 40 mg single and daily).","whyItMatters":"CGRP (calcitonin gene-related peptide) is the central target in modern migraine treatment, but most anti-CGRP drugs are injectable antibodies requiring monthly or quarterly administration. Zavegepant's nasal spray delivery offers on-demand treatment with rapid onset — peak levels in 30 minutes is faster than oral medications and comparable to subcutaneous injection. This phase 1 data established the foundational safety and pharmacokinetic profile that enabled zavegepant's eventual FDA approval as the first intranasal CGRP antagonist for acute migraine.","specificNumbers":"","methodology":"Two single-site, phase 1, randomized, double-blind, placebo-controlled studies in healthy adults. The single ascending dose (SAD) study enrolled 72 participants across nine dose cohorts (0.1-40 mg). The multiple ascending dose (MAD) study enrolled 72 participants across six cohorts (5-40 mg daily). Pharmacokinetic parameters including Tmax, Cmax, and AUC were characterized. Safety assessments included adverse event monitoring, ECG monitoring, and liver function tests.","limitations":"Phase 1 studies are designed for safety and pharmacokinetics, not efficacy — these trials could not determine whether zavegepant actually treats migraines. The participants were healthy adults, not migraine patients, so tolerability may differ in the target population. The study periods were relatively short, and very long-term safety data would come from later-phase trials and post-marketing surveillance. Sample sizes of 72 per study are standard for phase 1 but may miss rare adverse events."},{"rthcId":"RPEP-10138","title":"Efficacy of Semaglutide and Other GLP-1 Agonists in Patients with Heart Failure With Preserved Ejection Fraction and Obesity: A Systemic Review and Meta-Analysis.","authors":"Beshr, Mohammed S; Shembesh, Rana H; Kara, Arwi Omar; Salama, Abdelaziz H; Arhaym, Esraa; Abuajamieh, Maram; Elhadi, Muhammed","year":2025,"journal":"Cardiology in review","doi":"10.1097/CRD.0000000000000915","pmid":"40243299","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10139","title":"The Cost-Effectiveness of Semaglutide and Tirzepatide for Patients With Knee Osteoarthritis and Obesity.","authors":"Betensky, Daniel J; Smith, Karen C; Katz, Jeffrey N; Yang, Catherine; Hunter, David J; Collins, Jamie E; Feldman, Candace H; Messier, Stephen P; Kim, Jason S; Selzer, Faith; Paltiel, A David; Losina, Elena","year":2025,"journal":"Annals of internal medicine, 178(11), 1549-1560","doi":"10.7326/ANNALS-24-03609","pmid":"40953447","tags":[],"studyType":"modeling","evidenceStrength":"moderate","keyFinding":"Tirzepatide provided greater health benefits at lower costs than semaglutide for patients with knee osteoarthritis and obesity, with an incremental cost-effectiveness ratio (ICER) of $57,400 per quality-adjusted life-year (QALY) versus diet and exercise. At a $100,000 per QALY willingness-to-pay threshold, tirzepatide had a 64% probability of being cost-effective compared to 34% for semaglutide.\n\nFor patients eligible for bariatric surgery, Roux-en-Y gastric bypass (RYGB) provided even greater health benefits at lower costs than both GLP-1 drugs, with an ICER of $30,700 per QALY versus laparoscopic sleeve gastrectomy.","whyItMatters":"Millions of people live with both knee osteoarthritis and obesity, conditions that worsen each other. GLP-1 receptor agonists like semaglutide and tirzepatide have shown they can reduce both weight and knee pain, but these drugs are expensive. This study provides decision-makers with concrete data showing that both drugs represent a reasonable investment in health outcomes, with tirzepatide offering the better value — important information as payers and health systems decide whether to cover these medications for osteoarthritis patients.","specificNumbers":"Tirzepatide ICER: $57,400/QALY · Semaglutide ICER: higher than tirzepatide · RYGB ICER: $30,700/QALY vs LSG · Baseline BMI: 40 kg/m² · Pain score: 71/100 · Tirzepatide cost-effective probability: 64% · Semaglutide: 34%","methodology":"The researchers used the Osteoarthritis Policy Model, a validated microsimulation model of knee osteoarthritis, to estimate lifetime health benefits and costs. They compared five weight loss strategies: semaglutide, tirzepatide, laparoscopic sleeve gastrectomy, Roux-en-Y gastric bypass, and diet and exercise. Input data came from published clinical trials and the U.S. Office of Health Policy. The base-case cohort had a mean BMI of 40 kg/m² and a pain score of 71 out of 100. Outcomes were measured in quality-adjusted life-years and costs from healthcare and societal perspectives.","limitations":"This is a modeling study based on published data rather than a head-to-head clinical trial. The results are sensitive to assumptions about medication costs, treatment efficacy, and baseline BMI. Real-world adherence, side effects, and long-term outcomes may differ from model inputs. Data were drawn from multiple sources, which may introduce heterogeneity."},{"rthcId":"RPEP-10140","title":"Weight loss reverses obesity-associated impairments in acute gastrointestinal stretch-induced suppression of food intake and glucose homeostasis.","authors":"Bethea, Maigen; Cook, Tyler; Mommandi, Marwa; McClennan, Andrew; Martin, Allison; Hendrix, Jasmine J; Hutch, Chelsea R; Lewis, Alfor; Seeley, Randy J; Fenselau, Henning; da Silva Teixeria, Silvania; Sandoval, Darleen A","year":2025,"journal":"Molecular metabolism, 102, 102260","doi":"10.1016/j.molmet.2025.102260","pmid":"41015152","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Intestinal stretch — independent of nutrients and gut hormones — suppresses food intake and improves glucose tolerance in mice. Using mannitol (a nonnutritive substance) to selectively stretch the intestine, researchers showed this mechanical signal acutely reduces eating and improves oral glucose tolerance without relying on GLP-1 signaling or vagal mechanosensation. Critically, diet-induced obesity impaired this stretch response, reducing both feeding suppression and neuronal activation in the nucleus of the solitary tract (NTS). Both dietary weight loss and vertical sleeve gastrectomy (VSG) restored the impaired stretch-induced feeding suppression and enhanced NTS neuronal activation. VSG specifically heightened NTS neuronal activation in response to oral (but not injected) glucose.","whyItMatters":"This study reveals a previously underappreciated mechanism for appetite control — pure physical stretching of the intestine, separate from nutrient sensing or gut hormone release. The finding that obesity breaks this mechanism (and that weight loss restores it) adds a new dimension to understanding why obese individuals struggle with satiety. It also provides insight into why bariatric surgery works: VSG may partially restore the gut's mechanical signaling to the brain.","specificNumbers":"","methodology":"Mouse study using mannitol to induce intestinal stretch without providing nutrients. Food intake, oral glucose tolerance, and brain neuronal activation (NTS) were measured in lean mice, diet-induced obese mice, and mice after weight loss (dietary intervention or vertical sleeve gastrectomy). Chemogenetic approaches inhibited GLP-1R and OxtR-expressing vagal afferents. Genetic and pharmacological strategies ablated GLP-1 signaling to test whether stretch effects were GLP-1-independent.","limitations":"Animal study in mice, which may not directly translate to human physiology. Mannitol-induced stretch is an artificial stimulus that may not perfectly replicate normal post-meal intestinal distension. The study focused on acute effects; chronic or repeated stretch responses were not assessed. Specific neuronal pathways mediating GLP-1-independent effects remain to be fully characterized."},{"rthcId":"RPEP-10141","title":"Biological variation of cardiac biomarkers in athletes during an entire sport season.","authors":"Beumer Prieto, Blanca; Moreno-Parro, Isabel; Sufrate-Vergara, Berta; Fabre-Estremera, Blanca; Buño Soto, Antonio; Fernández-Calle, Pilar; Díaz-Garzón Marco, Jorge","year":2025,"journal":"Clinical chemistry and laboratory medicine, 63(5), 987-994","doi":"10.1515/cclm-2024-1203","pmid":"39865503","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10142","title":"Artificial intelligence and natural language processing of patient narratives to evaluate semaglutide for weight loss.","authors":"Bhagavathula, Akshaya Srikanth","year":2025,"journal":"Annals of epidemiology, 111, 9-13","doi":"10.1016/j.annepidem.2025.09.003","pmid":"40957545","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 95 reviewers reporting both weight loss amounts and treatment duration, users taking semaglutide for more than 60 days achieved mean weight loss of 32.2 ± 3.1 lbs (14.6 kg).\n\nThe most frequently mentioned side effects were: nausea (46.9%), headache (18.4%), vomiting (14.3%), fatigue (9.2%), and dizziness (4.8%). Sentiment analysis showed the highest satisfaction scores in the ≤30-day group (mean: 3.38 on a 5-point scale). Topic modeling identified dominant themes: appetite suppression, medication cost and access barriers, and long-term experiences. Cluster analysis revealed distinct user profiles including a 'super-responder' group and a side-effect-burdened group.","whyItMatters":"Clinical trials are conducted under ideal conditions with selected patients. Real-world patient experiences can differ significantly. This AI-powered approach to mining patient reviews provides a scalable way to understand how peptide drugs like semaglutide actually perform in diverse populations, including patient satisfaction, common complaints, and access challenges that clinical trials don't capture. The identification of super-responder and side-effect-burdened clusters could help personalize treatment expectations.","specificNumbers":"","methodology":"Retrospective cross-sectional analysis of 772 user-generated reviews of semaglutide from Drugs.com (July 2021 - March 2025). Sentiment analysis used a BERT transformer model on a five-point scale. Topic modeling employed Latent Dirichlet Allocation (LDA) and Latent Semantic Analysis (LSA) to identify dominant themes. Cluster analysis segmented users by weight loss outcomes and side effect severity. A subset of 95 reviewers with explicit weight and duration data was analyzed for efficacy metrics.","limitations":"Patient reviews on Drugs.com are self-selected and not representative of all semaglutide users. Only 95 of 772 reviewers reported specific weight loss and duration data. Reviews may be biased toward extreme experiences (very positive or very negative). No verification of reported weights, doses, or treatment durations was possible. The BERT sentiment model may not perfectly capture nuanced medical experiences. Side effect frequencies from reviews are not comparable to clinical trial incidence rates due to different denominators and reporting methods."},{"rthcId":"RPEP-10143","title":"Profiling Cytosolic Drug Delivery in Mammalian Cells: A Generalizable Assay for Intracellular Accumulation.","authors":"Bhandari, Sobika; Ongwae, George M; Dash, Rachita; Liu, Zichen; Chordia, Mahendra D; He, Yuchen; Pires, Marcos M","year":2025,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2025.06.03.656700","pmid":"40501898","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10144","title":"Effect of GLP-1 receptor agonists on body composition.","authors":"Bhandarkar, Akhila; Bhat, Sowrabha; Kapoor, Nitin","year":2025,"journal":"Current opinion in endocrinology, diabetes, and obesity, 32(6), 279-285","doi":"10.1097/MED.0000000000000934","pmid":"41076575","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10145","title":"Contemporary and Emerging Therapeutics in Cardiovascular-Kidney-Metabolic (CKM) Syndrome: In Memory of Professor Akira Endo.","authors":"Bharaj, Inderjeet Singh; Brar, Ajit; Kacheria, Aayushi; Purewal, Karen; Simister, Austin; Thirupathy, Umabalan; Gupta, Palak; Kahlon, Jasraj; Munaim, Juzer; Thwe, Ei Ei; Ibrahim, Samer; Martinez Vargas, Valerie; Vijayaraghavan, Krishnaswami","year":2025,"journal":"Biomedicines, 13(9)","doi":"10.3390/biomedicines13092192","pmid":"41007755","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10146","title":"The influence of renal impairment on the pharmacokinetics of rimegepant: Results of a phase 1, open-label, single-dose, parallel-group study.","authors":"Bhardwaj, Rajinder; Morris, Beth; Bertz, Richard; Matschke, Kyle; Croop, Robert; Liu, Jing","year":2025,"journal":"Headache, 65(8), 1381-1393","doi":"10.1111/head.15041","pmid":"40859716","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10147","title":"Efficacy and safety of incretin co-agonists: Transformative advances in cardiometabolic healthcare.","authors":"Bhat, Sowrabha; Fernandez, Cornelius J; Lakshmi, Vijaya; Pappachan, Joseph M","year":2025,"journal":"World journal of cardiology, 17(8), 107991","doi":"10.4330/wjc.v17.i8.107991","pmid":"40949933","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review maps the incretin co-agonist landscape across multiple drug classes. GLP-1 receptor agonists improve glycated hemoglobin, weight, lipid profiles, and liver fat, with many reducing major adverse cardiovascular events (MACE). The oral GLP-1RA orforglipron achieves approximately 15% weight reduction.\n\nTirzepatide, the first approved dual GIP/GLP-1 agonist, offers comparable efficacy with notably fewer gastrointestinal side effects than GLP-1 monoagonists. Triple agonists targeting GLP-1, GIP, and glucagon receptors (retatrutide, efocipegtrutide) have demonstrated the highest pharmacotherapy-achievable weight loss to date. Emerging combinations include GLP-1/amylin agonists (CagriSema, amycretin) and peptide YY/GLP-1 dual agonists.","whyItMatters":"Obesity and type 2 diabetes are global epidemics driving cardiovascular disease. Incretin co-agonists represent the most significant pharmacological advance in metabolic medicine in decades, with each new generation of multi-receptor agonists achieving greater weight loss and broader cardiometabolic benefits. Understanding this rapidly evolving drug landscape is essential for clinicians and researchers.","specificNumbers":"","methodology":"This is an evidence review synthesizing data from clinical trials and published studies on incretin-based therapies. The authors compiled efficacy and safety data across GLP-1 receptor agonists, dual agonists, triple agonists, and emerging combination peptide drugs to provide a comprehensive overview of the cardiometabolic benefits.","limitations":"As a review article, this paper synthesizes existing trial data rather than presenting original research. The abstract does not detail specific trial sizes, follow-up periods, or comparative effect sizes across drug classes. Many of the newer agents (retatrutide, efocipegtrutide, amycretin) are still in clinical trials, so long-term safety and real-world effectiveness data are limited."},{"rthcId":"RPEP-10148","title":"Impact of GLP-1 receptor agonists on cranial nerve palsies in type 2 diabetes: a retrospective cohort study.","authors":"Bhatia, Ronak; Al-Bana, Huda; Mohamed, Khalid; Amaefuna, Chimezie; Johnson, Stephanie; Munasinghe, Banuja; Elkomi, Rawan; Gillani, Syed Fahad; Beyene, Elizabeth; Bisrat, Mekdem; Michael, Miriam","year":2025,"journal":"Journal of neurology, 273(1), 16","doi":"10.1007/s00415-025-13560-9","pmid":"41361010","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10149","title":"Neuroinflammatory crosstalk in migraine: consolidated activity of rizatriptan and meloxicam in suppressing CGRP-induced nociception and COX-mediated inflammation.","authors":"Bhatia, Vandana; Vikram, Vir; Rattan, Aditya; Chandel, Anjali; Ashawat, M S","year":2025,"journal":"Inflammopharmacology, 33(7), 3871-3883","doi":"10.1007/s10787-025-01848-1","pmid":"40668531","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The study presents the rationale and evidence for SYMBRAVO, a dual-pathway pharmacological approach combining rizatriptan (a triptan targeting CGRP-induced nociception via serotonin 5-HT1B/1D receptors) and meloxicam (a selective COX-2 inhibitor reducing inflammatory prostaglandins).\n\nThe authors argue that CGRP and COX pathways interact in migraine through neuroinflammatory crosstalk, where CGRP-mediated neurogenic inflammation amplifies COX-dependent prostaglandin production and vice versa. Targeting both simultaneously could improve efficacy, reduce the dose needed for each drug, and minimize side effects compared to monotherapy.","whyItMatters":"Despite available treatments, many migraine patients still experience inadequate relief. Single-drug approaches often fail because migraine involves multiple interconnected pathways. This combination strategy targeting both CGRP-mediated pain and COX-mediated inflammation could represent a more effective treatment paradigm, particularly for patients who don't respond well to triptans or NSAIDs alone.","specificNumbers":"","methodology":"This is a review and pharmacological analysis that explores the molecular basis, drug interactions, and clinical potential of combining rizatriptan and meloxicam for migraine. The authors examine the neuroinflammatory crosstalk between CGRP and COX pathways and assess how dual targeting could overcome limitations of single-drug approaches.","limitations":"The abstract does not present original clinical trial data or specific efficacy outcomes for the SYMBRAVO combination. This appears to be primarily a review and pharmacological rationale rather than a clinical study with patient data. The specific synergistic benefit of this combination versus other drug pairings needs clinical validation."},{"rthcId":"RPEP-10150","title":"Tirzepatide leads to weight reduction in people with obesity due to MC4R deficiency.","authors":"Bhatnagar, Pallav; Ahmad, Nadia N; Li, Xuan; Coghlan, Matthew; Kaplan, Lee M; Farooqi, I Sadaf","year":2025,"journal":"Nature medicine, 31(10), 3294-3296","doi":"10.1038/s41591-025-03913-2","pmid":"40858971","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10151","title":"Gastrointestinal side effects of the non-peptide GLP-1 receptor agonists: A systematic review and meta-analysis.","authors":"Bhattarai, Himal Bikram; Paudel, Basanta Sharma; Parajuli, Sandesh Raman; Dahal, Krishna; Shah, Sangam; Bhattarai, Madhur; Baral, Bidisha; Karki, Bibek; Basnet, Bibhusan; Bhandari, Amit; Sah, Ranjit; Khanal, Amit; Ahmed, Khalid; McDonald, Philip","year":2025,"journal":"Medicine, 104(52), e46671","doi":"10.1097/MD.0000000000046671","pmid":"41465949","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10152","title":"Cardiovascular Pharmacotherapy and Glucose Metabolism: The Good, the Bad and the Unsightly.","authors":"Bianchettin, Rosana G; Poirier, Paul; Lopez-Jimenez, Francisco; Lavie, Carl J; Piché, Marie-Eve","year":2025,"journal":"American journal of cardiovascular drugs : drugs, devices, and other interventions","doi":"10.1007/s40256-025-00777-2","pmid":"41247648","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10153","title":"Cysteine pattern barcoding-based dataset filtration enhances the machine learning-assisted interpretation of Conus venom peptide therapeutics.","authors":"Bibi, Rimsha; Qasmi, Noshaba; Rashid, Sajid","year":2025,"journal":"PloS one, 20(7), e0327578","doi":"10.1371/journal.pone.0327578","pmid":"40644439","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10154","title":"Dietary glycocalyx mimetic reduces vascular risk in Type 2 diabetes: evidence from urinary peptidomic classifiers in a South-Asian Surinamese Cohort.","authors":"Biglari, Sajjad; Yuan, Lushun; Mischak, Harald; Siwy, Justyna; Latosinska, Agnieszka; Banasik, Miroslaw; van den Berg, Bernard M","year":2025,"journal":"Diabetes research and clinical practice, 229, 112931","doi":"10.1016/j.diabres.2025.112931","pmid":"41052726","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Glycocalyx-mimetic supplementation significantly reduced heart failure risk scores (HF2) by a mean of -0.58 (95% CI: -0.83 to -0.33, adjusted p<0.001) as measured by urinary peptidomic classifiers. The supplement altered 17 urinary peptides, primarily decreasing collagen-derived fragments, suggesting improved extracellular matrix turnover. Coronary artery disease (CAD160) and chronic kidney disease (CKD273) risk scores were unchanged. Neither the fasting-mimicking diet nor placebo produced meaningful changes in any classifier.","whyItMatters":"Type 2 diabetes dramatically increases cardiovascular risk. This study shows a dietary supplement can measurably improve a validated biomarker of heart failure risk — using cutting-edge peptidomic technology to detect changes at the molecular level. The glycocalyx (the protective lining of blood vessels) is damaged in diabetes, and this is one of the first interventional studies showing it can be therapeutically targeted with a supplement.","specificNumbers":"","methodology":"This was a follow-up analysis of a prior placebo-controlled trial. Forty-four South-Asian Surinamese adults with type 2 diabetes were randomly allocated to 12 weeks of daily glycocalyx-mimetic capsules (n=18), placebo (n=14), or a 5-day fasting-mimicking diet repeated every 4 weeks (n=12). Urine samples at baseline and week 12 were analyzed using capillary electrophoresis-mass spectrometry. Three pre-validated peptide classifiers scored risk for heart failure, coronary artery disease, and chronic kidney disease.","limitations":"Small sample size of only 44 participants across three groups. The study population was limited to South-Asian Surinamese adults, which may limit generalizability. Only urinary peptide biomarkers were measured — no hard clinical endpoints like actual heart failure events. CAD and CKD risk scores did not change, limiting the scope of cardiovascular benefit. The 12-week duration may be too short to detect all effects."},{"rthcId":"RPEP-10155","title":"Obesity as a Part of Polycysric Ovary Syndrome (PCOS)-A Review of Pathophysiology and Comprehensive Therapeutic Strategies.","authors":"Bila, Jovan; Dotlic, Jelena; Andjic, Mladen; Ivanovic, Katarina; Micic, Jelena; Tulic, Lidija; Pupovac, Miljan; Stojnic, Jelena; Vukovic, Ivana; Ivanovic, Stefan","year":2025,"journal":"Journal of clinical medicine, 14(16)","doi":"10.3390/jcm14165642","pmid":"40869469","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies GLP-1 receptor agonists as effective treatments that improve both metabolic and reproductive outcomes in PCOS. The key recommendation is that PCOS patients with insulin resistance and obesity would benefit most from combination therapy with metformin and GLP-1 receptor agonists, which provides comprehensive treatment for both the reproductive and metabolic aspects of the condition.\n\nOther effective interventions include myoinositol (for ovarian function), resveratrol (metabolic and reproductive benefits), and bariatric surgery for severe obesity. Lifestyle modifications remain the first-line approach.","whyItMatters":"PCOS is the most common endocrine disorder in women of reproductive age, affecting 6-12% of women. Obesity significantly worsens PCOS symptoms and complicates fertility. GLP-1 receptor agonists, already widely used for diabetes and obesity, represent an emerging treatment option that uniquely addresses multiple aspects of PCOS — weight, insulin resistance, hormonal balance, and reproductive function.","specificNumbers":"","methodology":"Non-systematic review of English-language papers published between 2010 and 2024, searched in MEDLINE. The review covers pathophysiology differences between obese and non-obese PCOS, clinical presentation, and therapeutic strategies including lifestyle, pharmacological, and surgical approaches.","limitations":"This is a non-systematic review, meaning the literature search was not comprehensive or reproducible. No meta-analysis was performed. The review covers studies from 2010-2024, and some newer evidence (e.g., tirzepatide for PCOS) may not be included. The specific GLP-1 receptor agonists studied in PCOS are not detailed. Evidence quality for GLP-1RAs in PCOS is still limited compared to their evidence in diabetes and obesity."},{"rthcId":"RPEP-10156","title":"Glucagon-Like Peptide-1 (GLP-1) receptor agonists in rheumatology: A review of current evidence and future directions.","authors":"Bilgin, Emre; Venerito, Vincenzo; Bogdanos, Dimitrios P","year":2025,"journal":"Autoimmunity reviews, 24(9), 103864","doi":"10.1016/j.autrev.2025.103864","pmid":"40617296","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10157","title":"Precision Targeting of Myeloid Cells via Peptide Dendrimer-Lipid Nanocarriers: A Novel Platform for Potent Cancer Immunotherapies.","authors":"Billing, Lawrence James; Martin, Liam; Henser-Brownhill, Tristan; Samangouei, Parisa; Leach, Adam; Knight, Phoebe; Apostolidou, Marina; Ladak, Aaqib; Nagel, Benita; Kwok, Albert","year":2025,"journal":"Advanced science (Weinheim, Baden-Wurttemberg, Germany), 12(46), e14417","doi":"10.1002/advs.202514417","pmid":"40971720","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10158","title":"Comparison of Dose Escalation Versus Switching to Tirzepatide Among People With Type 2 Diabetes Inadequately Controlled on Lower Doses of Dulaglutide : A Randomized Clinical Trial.","authors":"Billings, Liana K; Winne, Linsey; Sharma, Palash; Gomez-Valderas, Elisa; Chivukula, K Karthik; Kwan, Anita Y M","year":2025,"journal":"Annals of internal medicine, 178(5), 609-619","doi":"10.7326/ANNALS-24-03849","pmid":"40183678","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10159","title":"Once-weekly IcoSema versus multiple daily insulin injections in type 2 diabetes management (COMBINE 3): an open-label, multicentre, treat-to-target, non-inferiority, randomised, phase 3a trial.","authors":"Billings, Liana K; Andreozzi, Francesco; Frederiksen, Marie; Gourdy, Pierre; Gowda, Amoolya; Ji, Linong; Pletsch-Borba, Laura; Suzuki, Ryo; Unnikrishnan, A G; Vianna, André G D","year":2025,"journal":"The lancet. Diabetes & endocrinology, 13(7), 556-567","doi":"10.1016/S2213-8587(25)00052-X","pmid":"40482670","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10160","title":"Acute dyspnoea in cancer patients: Prevalence of acute heart failure, resource use and diagnostic accuracy of natriuretic peptides.","authors":"Bima, Paolo; Wussler, Desirée; Lopez-Ayala, Pedro; Belkin, Maria; Nowak, Albina; Lin, Xueting; Strebel, Ivo; Sgueglia, Fabiana; Michou, Eleni; Papachristou, Androniki; Chollet, Laureve; Popescu, Codruta; Kozhuharov, Nikola; Shrestha, Samyut; Kuster, Gabriela; Rentsch, Katharina; Von Eckardstein, Arnold; Binder, Mascha; Mahfoud, Felix; Breidthardt, Tobias; Mueller, Christian","year":2025,"journal":"European journal of heart failure, 27(11), 2100-2111","doi":"10.1002/ejhf.3752","pmid":"40583498","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10161","title":"Evaluating the Impact of Tirzepatide on Clinical Outcomes in Patients With Heart Failure.","authors":"Bin Abdul Malik, Mohammad Hamza; Khan, Nasar Nasrullah; Chowdhari, Mehreen Jawed; Rafiq, Muhammad Kashif; Ali, Muhammad; Lnu, Sadia; Ramzan, Hafiza Sobia; Ahmed, Mwahib Mohamed; Khatoon, Fahmida","year":2025,"journal":"Cureus, 17(4), e82118","doi":"10.7759/cureus.82118","pmid":"40357081","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10162","title":"Evaluation of Pre-Treatment Assessment of Semaglutide Users: Balancing the Benefits of Weight Loss vs. Potential Health Consequences.","authors":"Bin Dayel, Faten F; Alanazi, Rakan J; Alenazi, Miteb A; Alkhalifah, Sahar; Alfaifi, Mohammed; Alghadeer, Sultan; Alwhaibi, Abdulrahman","year":2025,"journal":"Healthcare (Basel, Switzerland), 13(15)","doi":"10.3390/healthcare13151827","pmid":"40805859","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10163","title":"Semaglutide in Diabetic Kidney Disease: Integrating Clinical Evidence with Mechanistic Insights.","authors":"Bin Dayel, Faten F","year":2025,"journal":"Healthcare (Basel, Switzerland), 13(22)","doi":"10.3390/healthcare13222922","pmid":"41302309","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10164","title":"The Potential Role of GLP1-RAs Against Anticancer-Drug Cardiotoxicity: A Scoping Review.","authors":"Biondi, Filippo; Madonna, Rosalinda","year":2025,"journal":"Journal of clinical medicine, 14(8)","doi":"10.3390/jcm14082705","pmid":"40283534","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10165","title":"Unlocking the potential of microfluidic assisted formulation of exenatide-loaded solid lipid nanoparticles.","authors":"Birro, Büşra Arpaç; Pesce, Cristiano; Tognetti, Francesco; Fragassi, Agnese; Casagrande, Lisa; Garofalo, Mariangela; Salmaso, Stefano; Caliceti, Paolo","year":2025,"journal":"International journal of pharmaceutics, 678, 125686","doi":"10.1016/j.ijpharm.2025.125686","pmid":"40354907","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10166","title":"Enabling organ- and injury-specific nanocarrier targeting via surface-functionalized PEG-b-PPS micelles for acute kidney injury.","authors":"Bishop, Boaz Y; Sharma, Swagat H; Tiwari, Ratnakar; Yuk, Simseok A; Almunif, Sultan; Quaggin, Susan E; Scott, Evan A; Kapitsinou, Pinelopi P","year":2025,"journal":"Nanoscale horizons, 10(12), 3423-3432","doi":"10.1039/d5nh00474h","pmid":"41048153","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10167","title":"Solid-State NMR Reveals Reorganization of the Aspergillus fumigatus Cell Wall Due to a Host-Defence Peptide.","authors":"Bishoyi, Ajit Kumar; van Neer, Jacq; Bahri, Salima; Lorenz, Sophie; de Cock, Hans; Baldus, Marc","year":2025,"journal":"Angewandte Chemie (International ed. in English), 64(35), e202509012","doi":"10.1002/anie.202509012","pmid":"40576059","tags":[],"studyType":"In Vitro / Mechanistic Study","evidenceStrength":"preliminary","keyFinding":"Using advanced solid-state NMR techniques, researchers revealed exactly how the host-defense peptide cathelicidin-2 attacks the cell wall of Aspergillus fumigatus, a drug-resistant fungus that causes life-threatening infections. The peptide disrupts galactosaminogalactan — a key component involved in the fungus's ability to cause invasive disease — and affects other polysaccharides and amino acids in the mobile cell wall domain.\n\nWith longer exposure, cathelicidin-2 also penetrates the rigid cell wall by enhancing water infiltration into normally hydrophobic regions, eventually reaching the plasma membrane. This two-phase attack — first targeting mobile wall components, then breaching rigid defenses — explains how the peptide can overcome the complex fungal cell wall barrier that makes antifungal drug development so challenging.","whyItMatters":"Aspergillus fumigatus is becoming increasingly resistant to azole antifungals, the standard treatment for invasive aspergillosis, which kills up to 50% of infected patients. Understanding how antimicrobial peptides penetrate fungal cell walls is critical for designing next-generation antifungal drugs. This study provides an atomic-level view of the mechanism that could guide the design of more effective peptide-based antifungals.","specificNumbers":"Solid-state NMR (1H and 13C detection) · Cathelicidin-2 vs. azole-resistant A. fumigatus · Galactosaminogalactan disrupted · Two-phase cell wall penetration mechanism · Published in Angewandte Chemie","methodology":"The researchers used tailored solid-state NMR spectroscopy (both proton and carbon-13 detection) to analyze the cell wall composition of Aspergillus fumigatus before and after exposure to cathelicidin-2. This allowed them to observe changes in specific polysaccharides and amino acids at the molecular level, distinguishing between effects on mobile and rigid cell wall domains at different exposure times.","limitations":"This is a purely structural/mechanistic study at the molecular level — no animal or clinical data. The NMR experiments are conducted under controlled laboratory conditions that may not fully replicate the complexity of in vivo fungal infection. The specific concentrations and exposure times used may differ from what would be therapeutically relevant."},{"rthcId":"RPEP-10168","title":"Modeling heart failure by induced pluripotent stem cell-derived organoids.","authors":"Bissoli, Irene; Alabiso, Francesco; Cosentino, Cristina; Seragnoli Chystyakova, Aleksandra; Ferré, Fabrizio; Alviano, Francesco; Marrazzo, Pasquale; Pignatti, Carla; Agnetti, Giulio; Regazzi, Romano; Flamigni, Flavio; D'Adamo, Stefania; Cetrullo, Silvia","year":2025,"journal":"Biochimica et biophysica acta. Molecular basis of disease, 1871(6), 167861","doi":"10.1016/j.bbadis.2025.167861","pmid":"40254266","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10169","title":"Engineered PepFect14 analog for efficient cellular delivery of oligonucleotides.","authors":"Biswas, Abhijit; Periyasamy, Kapilraj; Maloverjan, Maria; Porosk, Ly; Arya, Geeta; Mehta, Sudhichan; Andla, Hanna; Raid, Raivo; Kisand, Vambola; Rätsep, Margus; Wengel, Jesper; Rebane, Ana; Pooga, Margus","year":2025,"journal":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 184, 117872","doi":"10.1016/j.biopha.2025.117872","pmid":"39891949","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"PF14-Lys (a lysine-substituted analog of PepFect14) showed superior delivery of splicing-switching oligonucleotides and siRNA compared to the original PF14 in reporter cell lines. The alpha-helical structure of PF14 was found to be essential for delivery — mutations disrupting the hydrophobic or cationic face abolished nanoparticle formation and cell entry. PF14-Lys efficiently delivered miR-146a into human primary keratinocytes, downregulating target genes. Most importantly, subcutaneously administered PF14-Lys-miR-146a nanoparticles suppressed inflammatory responses in a mouse model of irritant contact dermatitis.","whyItMatters":"RNA-based therapeutics (siRNA, microRNA, antisense oligonucleotides) hold enormous potential for treating diseases from cancer to inflammatory conditions, but getting them inside cells efficiently and safely remains a major barrier. Cell-penetrating peptides offer a promising solution, and this study shows that rational peptide engineering — even simple amino acid substitutions — can meaningfully improve delivery performance. The successful in vivo demonstration in skin inflammation brings this technology closer to practical clinical applications.","specificNumbers":"","methodology":"Researchers introduced point mutations into PepFect14's peptide sequence and predicted modified CPP characteristics computationally. Biophysical methods analyzed peptide structure and ability to form nanoparticles with oligonucleotides. Delivery was tested using splicing-switching oligonucleotides and siRNA in reporter cell lines, and miR-146a in human primary keratinocytes. In vivo testing involved subcutaneous injection of PF14-Lys-miR-146a nanoparticles in a mouse model of irritant contact dermatitis.","limitations":"The in vivo testing was limited to a single mouse model (irritant contact dermatitis) with subcutaneous injection. Bioavailability, toxicity profiling, and pharmacokinetics were not detailed. The study did not compare PF14-Lys to other state-of-the-art delivery systems like lipid nanoparticles. Long-term safety and immune responses to repeated peptide administration were not assessed. The mechanism by which lysine substitution improves delivery is not fully elucidated beyond structural observations."},{"rthcId":"RPEP-10170","title":"Lead Informed Artificial Intelligence Mining of Antitubercular Host Defense Peptides.","authors":"Biswas, Diptomit; Benson, Sara; Matunis, Aidan; Gebretsadik, Gebremichal; Wertz, Adam; StPierre, Ben J; Schacht, Nathan; Yan, Yue; Gebremichael, Hanna Y; Wong, Pak Kin; Baughn, Anthony D; Medina, Scott H","year":2025,"journal":"Biomacromolecules, 26(5), 3167-3179","doi":"10.1021/acs.biomac.5c00244","pmid":"40310992","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10171","title":"Associations of Serum GIP, GLP-1, and DPP-4 with Metabolic and Hormonal Profiles and Tobacco Exposure in Women with Polycystic Ovary Syndrome.","authors":"Bizoń, Anna; Borkowska, Julia; Franik, Grzegorz; Piwowar, Agnieszka","year":2025,"journal":"International journal of molecular sciences, 26(15)","doi":"10.3390/ijms26157097","pmid":"40806228","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10172","title":"Cone snail venom-inspired somatostatin receptor 4 (SSTR4) agonists as new drug leads for peripheral pain.","authors":"Bjørn-Yoshimoto, Walden E; Ramiro, Iris Bea L; Koch, Thomas Lund; Engholm, Ebbe; Yeung, Ho Yan; Sørensen, Kasper K; Goddard, Carolyn M; Jensen, Kathrine L; Smith, Nicholas A; Martin, Laurent F; Smith, Brian J; Madsen, Kenneth L; Jensen, Knud J; Patwardhan, Amol; Safavi-Hemami, Helena","year":2025,"journal":"Scientific reports, 15(1), 42638","doi":"10.1038/s41598-025-26820-5","pmid":"41315638","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10173","title":"FATP2 at the crossroads of fatty acid transport, lipotoxicity, and complex disease.","authors":"Black, Paul N; DiRusso, Concetta C","year":2025,"journal":"The Journal of clinical investigation, 135(23)","doi":"10.1172/JCI199873","pmid":"41321315","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10174","title":"Vitamin D in Atopic Dermatitis: Role in Disease and Skin Microbiome.","authors":"Blady, Karolina; Pomianowski, Bartosz; Strugała, Miłosz; Smółka, Leon; Kursa, Karolina; Stanek, Agata","year":2025,"journal":"Nutrients, 17(22)","doi":"10.3390/nu17223584","pmid":"41305634","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10175","title":"Identifying High-Risk Obese Individuals Without Diabetes for GLP-1RA Therapy Using Coronary CTA.","authors":"Blair, Camila V; Huck, Daniel; Besser, Stephanie A; Cardoso, Rhanderson; Shiyovich, Arthur; Berman, Adam N; Biery, David W; Weber, Brittany N; Petranovic, Milena; Nasir, Khurram; Hedgire, Sandeep; Plutzky, Jorge; Cannon, Christopher; Di Carli, Marcelo F; Ghoshhajra, Brian B; Trinquart, Ludovic; Blankstein, Ron","year":2025,"journal":"JACC. Advances, 4(8), 101995","doi":"10.1016/j.jacadv.2025.101995","pmid":"40682896","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 5,173 individuals with BMI ≥27, those with obstructive coronary artery disease (≥50% blockage) had a 71% higher risk of cardiovascular events compared to those with no disease (adjusted HR: 1.71; 95% CI: 1.21-2.42; P = 0.002). At 4 years, event rates were 7.8% for obstructive CAD and 7.7% for extensive nonobstructive CAD — comparable to the 9.7% rate in the SELECT trial's control arm. The estimated number needed to treat with semaglutide was 66-67, close to SELECT's 56.","whyItMatters":"The SELECT trial proved semaglutide reduces cardiovascular events in obese people with established heart disease but without diabetes. However, many people at high cardiovascular risk don't have a diagnosed heart condition yet. This study shows that a common imaging test — coronary CT angiography — can identify these hidden high-risk individuals, potentially expanding the population who could benefit from GLP-1 receptor agonist therapy.","specificNumbers":"","methodology":"This was a retrospective cohort study of 5,173 adults aged 45 or older with BMI ≥27 who underwent coronary CT angiography at two medical centers. Researchers excluded those with prior heart attack, revascularization, stroke, diabetes, end-stage kidney disease, or cancer. They categorized coronary artery disease severity and used Cox regression models to assess the relationship between disease severity and cardiovascular outcomes (death, heart attack, or stroke).","limitations":"This was a retrospective study, so it cannot prove that semaglutide would actually reduce events in the identified population — only a randomized trial could confirm that. The number needed to treat was estimated by applying SELECT trial effect sizes, not from actual treatment data. The study population came from two academic centers, which may not represent broader populations. Selection bias exists since participants had clinical reasons for getting CT scans."},{"rthcId":"RPEP-10176","title":"Fremanezumab: Pediatric First Approval.","authors":"Blair, Hannah A","year":2025,"journal":"Paediatric drugs, 27(6), 771-775","doi":"10.1007/s40272-025-00722-5","pmid":"41021201","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10177","title":"GLP-1 agonists to slow down Parkinson's progression? The quest continues.","authors":"Bloem, Bastiaan R; Macklin, Eric A; Schwarzschild, Michael A","year":2025,"journal":"Med (New York, N.Y.), 6(4), 100645","doi":"10.1016/j.medj.2025.100645","pmid":"40220748","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10178","title":"How Glucagon-Like Peptide-1 Medications Are Depicted in Instagram Posts Regarding Women's Health, Nontraditional Access, and Barriers to Access: Content Analysis.","authors":"Bloom, Brittnie E; Bragg, Marie A; Jay, Melanie R; Harel, Daphna; Cline, Camile; Crowe, Matthew; Montoya, Avery; Muthuramalingam, Sandhya; Santana, Roberto; Albert, Stephanie L","year":2025,"journal":"Journal of medical Internet research, 27, e66400","doi":"10.2196/66400","pmid":"40905615","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10179","title":"Repurposing the hypoglycaemic agents for neuroinflammation, a comprehensive review.","authors":"Blossom, Vandana; Ullal, Sheetal D; Rai, Rajalakshmi; D Souza, Melisha Michael; Kalluraya, P Gopal Govind; Dixit, Ayush; Jiji, P J; Murlimanju, B V","year":2025,"journal":"3 Biotech, 15(9), 281","doi":"10.1007/s13205-025-04455-7","pmid":"40771585","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies several diabetes drugs with neuroinflammatory potential:\n\n- Liraglutide (GLP-1 receptor agonist): Showed encouraging effects in regulating blood sugar while possibly lowering neuroinflammation; obese patients saw decreased neuroinflammatory markers alongside weight loss and glycemic improvements\n- Gliburide (sulfonylurea): Effectively inhibits the NLRP3 inflammasome, suggesting potential for neuroinflammation-related disorders\n- Sulfonylureas: Mouse studies showed anti-neuroinflammatory properties by targeting NLRP3 and modulating ERK/STAT3/NF-κB signaling\n- Empagliflozin (SGLT2 inhibitor): Offered neuroprotection and helped neurovascular remodeling for cognitive function\n- Insulin, metformin, thiazolidinediones: All have potential for repurposing against neuroinflammation\n\nThe shared pathway through NLRP3 inflammasome and IL-1β connects diabetes and neuroinflammation mechanistically.","whyItMatters":"Neurodegenerative diseases like Alzheimer's and Parkinson's have limited treatment options. People with diabetes have significantly higher risk of developing these conditions. If existing diabetes drugs — particularly GLP-1 agonists — can simultaneously address both metabolic and neuroinflammatory problems, millions of patients could benefit from treatments already proven safe.","specificNumbers":"","methodology":"Comprehensive narrative review synthesizing published research on the shared pathways between diabetes and neuroinflammation, and the potential for repurposing anti-diabetic medications for neurological conditions.","limitations":"Most evidence for anti-neuroinflammatory effects comes from animal models, not human clinical trials. The review is narrative rather than systematic, potentially introducing selection bias. Drug concentrations needed for neuroprotection may differ from those used for diabetes management. Whether brain penetration is sufficient for all listed drugs is not fully addressed."},{"rthcId":"RPEP-10180","title":"Use of glucagon-like peptide 1 receptor agonist to sustain patients off basal-bolus insulin regimens.","authors":"Blumenfeld, Lauren; Morgan, Jillian; Morgan, Timothy C; Thomas, Ashley M","year":2025,"journal":"Journal of the American Pharmacists Association : JAPhA, 65(1), 102288","doi":"10.1016/j.japh.2024.102288","pmid":"39527981","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10181","title":"Ileum targeted semaglutide delivery and pharmacokinetic study in an experimental porcine animal model via oesophagogastroduodenoscopic administration.","authors":"Blümlinger, Michael; Hamar, Flora; Werle, Martin; Föger, Florian; Hrouda, Martina; Ludewig, Eberhard; Huck, Christian; Heiss, Martin; Schwarz, Lukas","year":2025,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 387, 114164","doi":"10.1016/j.jconrel.2025.114164","pmid":"40850442","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10182","title":"Somatostatin receptor 2 targeting peptide modifications for peptide-drug conjugate treatment of small cell lung cancer.","authors":"Bo, Qing; Zhang, Meng-Ge; Yang, Fan; Zheng, Yong; Li, Ze-Lin; Zheng, Yan-Min; Wu, Fang-Ming; Liang, Jun; Zhou, Li; Li, Dong-Sheng; Wu, Yun; Tian, Chang-Lin; Lv, Pei; Shi, Pan","year":2025,"journal":"Acta pharmacologica Sinica, 46(12), 3291-3301","doi":"10.1038/s41401-025-01584-w","pmid":"40533489","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10183","title":"Comparative efficacy of pharmacological interventions on metabolic and hormonal outcomes in polycystic ovary syndrome: a Network Meta-Analysis of Randomized controlled trials.","authors":"Bo, Yali; Zhao, Jie; Liu, Chengjiang; Yu, Ting","year":2025,"journal":"BMC women's health, 25(1), 64","doi":"10.1186/s12905-025-03594-6","pmid":"39955537","tags":["glp-1-agonists"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Adding GLP-1 receptor agonists to standard PCOS therapy significantly outperformed standard therapy alone across multiple metabolic measures: body weight dropped by 3.44 kg more, BMI by 2.05 points, and waist circumference by 4.39 cm. The combination also improved insulin resistance (HOMA-IR reduced by 1.29) and fasting blood glucose.\n\nOrlistat stood out for a different reason — it was the most effective at reducing testosterone levels (the key hormonal driver of PCOS symptoms) and raising HDL cholesterol. The overall conclusion supports combination pharmacotherapy for comprehensive PCOS management.","whyItMatters":"PCOS affects up to 13% of women of reproductive age and involves a tangled web of metabolic and hormonal problems — insulin resistance, excess androgens, weight gain, and cardiovascular risk. This meta-analysis provides the strongest evidence to date that GLP-1 drugs, already transforming obesity and diabetes care, can be a powerful addition to PCOS treatment by addressing the metabolic component.","specificNumbers":"29 RCTs · n=1,476 · GLP-1+standard: BW -3.44 kg · BMI -2.05 · WC -4.39 cm · HOMA-IR -1.29 · Orlistat: testosterone SMD -2.16 · HDL-C SMD +0.90 · ≥12 weeks follow-up","methodology":"Systematic review and network meta-analysis of 29 randomized controlled trials including 1,476 women with PCOS. Researchers searched PubMed, MEDLINE, Embase, and Web of Science through October 2023. Only RCTs with at least 12 weeks of follow-up were included. Outcomes measured included body weight, BMI, waist circumference, testosterone, SHBG, lipid profiles, HOMA-IR, fasting glucose, and fasting insulin. Network meta-analysis allowed indirect comparison between treatments that hadn't been studied head-to-head.","limitations":"The 29 included trials varied in specific GLP-1 drugs used, doses, and definitions of standard therapy. With 1,476 total participants spread across multiple comparison arms, individual comparisons may be underpowered. Most trials had 12-week minimum follow-up, so long-term effects and sustainability of improvements are unknown. The analysis could not evaluate fertility outcomes or menstrual regularity."},{"rthcId":"RPEP-10184","title":"Cardiovascular Disease Update: Heart Failure Update.","authors":"Bobeck, Kevin A; Recidoro, Anthony M; Sapoval, Joseph M; Smith, Dustin K","year":2025,"journal":"FP essentials, 555, 24-31","doi":null,"pmid":"40829047","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10185","title":"Modification of the Association of B-Type Natriuretic Peptides With Mortality and Hospitalization Outcomes by Sex.","authors":"Bobrowski, David; Abdel-Qadir, Husam; McNaughton, Candace D; Chu, Anna; Wang, Xuesong; Austin, Peter C; Doumouras, Barbara S; Abdul-Samad, Karem; Kavsak, Peter A; Farkouh, Michael E; Januzzi, James L; Ross, Heather J; Lee, Douglas S","year":2025,"journal":"JACC. Advances, 4(8), 101999","doi":"10.1016/j.jacadv.2025.101999","pmid":"40712268","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10186","title":"Dulaglutide 1.5 mg Significantly Improves Glycemic Control and Lowers LDL-Cholesterol and Body Weight in Romanian Patients with Type 2 Diabetes.","authors":"Bobu, Amelian Madalin; Turliuc, Serban; Cucu, Andrei Ionut; Onofriescu, Alina; Dascalu, Cristina Gena; Costea, Claudia Florida; Patrascanu, Emilia; Morosan, Anca Petruta; Haisan, Anca; Filip, Carmen Nicoleta; Covali, Roxana; Buzduga, Catalin Mihai; Botnariu, Gina; Enache, Irina Iuliana Costache","year":2025,"journal":"Journal of clinical medicine, 14(10)","doi":"10.3390/jcm14103536","pmid":"40429530","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10187","title":"Case Report: Rhabdomyolysis following initiation of tirzepatide.","authors":"Bodanowitz, Jonas Michael; Mattes, Isabell; Loebermann, Micha; Fritzsche, Carlos","year":2025,"journal":"Frontiers in pharmacology, 16, 1660785","doi":"10.3389/fphar.2025.1660785","pmid":"40910008","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A 66-year-old woman developed rhabdomyolysis with markedly elevated creatine kinase levels following her first administration of an increased dose of tirzepatide. The temporal relationship between drug initiation and symptom onset strongly suggested tirzepatide as the trigger. Laboratory findings normalized within 4 days of drug discontinuation and supportive IV fluid therapy. The authors report this as the first documented case of rhabdomyolysis associated with tirzepatide.","whyItMatters":"Tirzepatide (Mounjaro/Zepbound) is one of the most widely prescribed new medications globally, used for both type 2 diabetes and weight loss. Identifying rare but serious adverse effects like rhabdomyolysis is critical for patient safety, especially given the widespread off-label use of this drug class for weight management.","specificNumbers":"","methodology":"This is a single-patient case report documenting the clinical presentation, laboratory findings, treatment, and outcome of rhabdomyolysis temporally associated with tirzepatide administration. The causality assessment was based on the temporal relationship and recovery after discontinuation.","limitations":"As a single case report, this represents the lowest level of clinical evidence. A causal relationship cannot be definitively established — the temporal association is suggestive but not conclusive. No rechallenge was performed, and other potential contributing factors may not have been fully excluded."},{"rthcId":"RPEP-10188","title":"Endogenous opiates and behavior: 2024.","authors":"Bodnar, Richard J","year":2025,"journal":"Peptides, 191, 171422","doi":"10.1016/j.peptides.2025.171422","pmid":"40532879","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10189","title":"VIP and PACAP enhance hippocampal neuronal cell proliferation especially GFAP-positive astrocytes, while PACAP inhibits neurite outgrowth.","authors":"Bodorova, Barbora; Mihalj, Denisa; Havranek, Tomas; Bacova, Zuzana; Bakos, Jan","year":2025,"journal":"Neuroscience letters, 855, 138230","doi":"10.1016/j.neulet.2025.138230","pmid":"40164327","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10190","title":"Clinical Pharmacokinetics of Atogepant in Healthy Japanese and White Adults.","authors":"Boinpally, Ramesh R; McNamee, Brian","year":2025,"journal":"Neurology and therapy, 14(1), 399-412","doi":"10.1007/s40120-024-00699-2","pmid":"39755896","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10191","title":"Mass Balance and Metabolism of 14C-Atogepant in Healthy Male Participants: Findings of a Phase 1 Clinical Trial.","authors":"Boinpally, Ramesh R; Chandrasekar, Pushpa; Rowe, Joshua M","year":2025,"journal":"Clinical and translational science, 18(11), e70382","doi":"10.1111/cts.70382","pmid":"41187001","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10192","title":"Evidence-based SGLT2 inhibitor and GLP-1 receptor agonist use by race in the VA healthcare system.","authors":"Bolden, Demetria M; Richardson, Vanessa; Salahuddin, Taufiq; Henderson, Kamal; Hess, Paul L; Raghavan, Sridharan; Saxon, David R; Ho, P Michael; Waldo, Stephen W; Schwartz, Gregory G","year":2025,"journal":"American journal of preventive cardiology, 22, 100966","doi":"10.1016/j.ajpc.2025.100966","pmid":"40275941","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 63,561 Veterans with type 2 diabetes and coronary artery disease across 84 VA medical centers (2015-2023), Black Veterans were 15% less likely to receive evidence-based GLP-1 receptor agonist prescriptions compared to White Veterans (adjusted OR 0.85, 95% CI 0.74-0.98, p=0.025).\n\nNo racial disparity was found for SGLT2 inhibitor prescribing (adjusted OR 0.96, 95% CI 0.89-1.04, p=0.32). However, overall uptake remained low for both drug classes: only 42% of eligible patients received SGLT2 inhibitors and 15% received GLP-1RAs by 2023, indicating widespread undertreatment regardless of race.","whyItMatters":"GLP-1 receptor agonists have proven cardiovascular benefits for patients with type 2 diabetes and heart disease. Finding that Black Veterans are less likely to receive these medications — even in the VA system, which has fewer economic barriers than private healthcare — suggests systemic factors beyond cost are driving the disparity. Addressing this gap could improve cardiovascular outcomes for an underserved population.","specificNumbers":"","methodology":"Retrospective cohort study using data from the VA Clinical Assessment, Reporting, and Tracking Program across 84 VA medical centers from 2015 to 2023. Researchers identified Veterans with type 2 diabetes and angiographically confirmed coronary artery disease who met eligibility criteria modeled on the EMPA-REG OUTCOME trial (for SGLT2i) or the LEADER trial (for GLP-1RA). Multivariable logistic regression estimated adjusted odds of receiving trial-concordant prescriptions by self-identified race.","limitations":"The study was limited to the VA healthcare system, which may not be generalizable to other settings. Self-identified race was used as the exposure variable, which doesn't capture the full complexity of racial identity or structural racism. The study could not determine the specific reasons for the prescribing disparity (e.g., provider bias, patient preference, clinical factors). Residual confounding is possible despite multivariable adjustment."},{"rthcId":"RPEP-10193","title":"An overview of randomized clinical trials of fixed-ratio combinations of basal insulin plus GLP-1RA (injectable therapy): Lessons for advancing therapy in people with type 2 diabetes.","authors":"Bolli, Geremia B; Porcellati, Francesca; Lucidi, Paola; Fanelli, Carmine G; Perseghin, Gianluca; Horowitz, Michael; Owens, David R","year":2025,"journal":"Diabetes, obesity & metabolism, 27 Suppl 7(Suppl 7), 14-25","doi":"10.1111/dom.16616","pmid":"40678871","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10194","title":"Semaglutide and walking capacity in people with symptomatic peripheral artery disease and type 2 diabetes (STRIDE): a phase 3b, double-blind, randomised, placebo-controlled trial.","authors":"Bonaca, Marc P; Catarig, Andrei-Mircea; Houlind, Kim; Ludvik, Bernhard; Nordanstig, Joakim; Ramesh, Chethana Kalmady; Rasouli, Neda; Sourij, Harald; Videmark, Alex; Verma, Subodh","year":2025,"journal":"Lancet (London, England), 405(10489), 1580-1593","doi":"10.1016/S0140-6736(25)00509-4","pmid":"40169145","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10195","title":"GLP-1 receptor agonists as promising anti-inflammatory agents in heart failure with preserved ejection fraction.","authors":"Bonfioli, Giovanni Battista; Rodella, Luca; Metra, Marco; Vizzardi, Enrico","year":2025,"journal":"Heart failure reviews, 30(1), 131-136","doi":"10.1007/s10741-024-10450-6","pmid":"39425816","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10196","title":"Understanding the Role of Glucagon-like Peptide-1 Receptor Agonists in the Treatment of Heart Failure.","authors":"Bonfioli, Giovanni Battista; Pagnesi, Matteo; Tomasoni, Daniela; Rakisheva, Amina; Metra, Marco","year":2025,"journal":"Cardiac failure review, 11, e19","doi":"10.15420/cfr.2025.10","pmid":"40901556","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10197","title":"Engineering of a Novel Amphibian Skin Peptide Isolated from Agua Rica Leaf Frog (Callimedusa ecuatoriana) into Active Antimicrobial Agents.","authors":"Bonilla-Jiménez, Stefanny; Espinosa de Los Monteros-Silva, Nina; Morán-Marcillo, Giovanna; Bermúdez-Puga, Sebastián; Terán-Valdez, Andrea; Almeida, José R; Proaño-Bolaños, Carolina","year":2025,"journal":"Antibiotics (Basel, Switzerland), 14(12)","doi":"10.3390/antibiotics14121186","pmid":"41463688","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A novel peptide (PTR-CE1) isolated from the skin secretion of an Ecuadorian leaf frog lacked antimicrobial activity due to a kink in its alpha-helix structure. By engineering two analogs with complete α-helix conformations, researchers created potent antimicrobial agents. PTR-CE1a showed broad-spectrum activity against all tested microorganisms with MIC values of 3.02–12.06 μM and only 7.5% hemolytic activity at its effective concentration. Both analogs were active against ampicillin-resistant bacteria.","whyItMatters":"Antibiotic resistance is a growing crisis, and nature's chemical arsenal — particularly from underexplored species — offers templates for new antibiotics. This study shows how a single structural fix (straightening an alpha-helix kink) can transform an inactive frog peptide into a potent, broad-spectrum antimicrobial with low toxicity to human cells.","specificNumbers":"","methodology":"Researchers isolated a novel peptide from the skin secretion of Callimedusa ecuatoriana (an Ecuadorian leaf frog) using molecular cloning of its mRNA precursor. Finding the native peptide inactive, they used computational tools to design two analogs (PTR-CE1a and PTR-CE1b) with complete alpha-helix structures. Both analogs were synthesized and tested for antimicrobial activity (minimum inhibitory concentration against multiple microorganisms including ampicillin-resistant bacteria) and hemolytic activity (toxicity to red blood cells).","limitations":"This was entirely an in vitro study — no animal or human testing was performed. The hemolytic activity, while low, still exists and would need further optimization. The study tested a limited panel of microorganisms. In vivo efficacy, stability, and pharmacokinetics are unknown."},{"rthcId":"RPEP-10198","title":"Cardiovascular Effectiveness of Semaglutide Versus Dulaglutide in Type 2 Diabetes.","authors":"Bonnesen, Kasper; Heide-Jørgensen, Uffe; Christensen, Diana H; Lash, Timothy L; Pedersen, Lars; Thomsen, Reimar W; Matthews, Anthony A; Schmidt, Morten","year":2025,"journal":"Pharmacoepidemiology and drug safety, 34(12), e70276","doi":"10.1002/pds.70276","pmid":"41334697","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10199","title":"Long-Term Effectiveness of Once-Weekly Semaglutide in Patients With Type 2 Diabetes Previously Treated With Insulin. A Multicentre Real-World Study.","authors":"Bonora, Benedetta Maria; Giaccari, Andrea; Consoli, Agostino; Broglio, Fabio; Avogaro, Angelo; Fadini, Gian Paolo","year":2025,"journal":"Diabetes/metabolism research and reviews, 41(4), e70045","doi":"10.1002/dmrr.70045","pmid":"40277315","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10200","title":"Peptide Receptor Radionuclide Therapy Improves Survival in Patients Who Progress After Resection of Gastroenteropancreatic Neuroendocrine Tumors.","authors":"Borbon, Luis C; Sherman, Scott K; Breheny, Patrick J; Chandrasekharan, Chandrikha; Menda, Yusuf; Bushnell, David; Bellizzi, Andrew M; Ear, P H; O'Dorisio, M Sue; O'Dorisio, Thomas M; Dillon, Joseph S; Howe, James R","year":2025,"journal":"Annals of surgical oncology, 32(2), 1136-1148","doi":"10.1245/s10434-024-16463-7","pmid":"39505730","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10201","title":"A review of the effects of different types of social behaviors on the recruitment of neuropeptides and neurotransmitters in the nucleus accumbens.","authors":"Borland, Johnathan M","year":2025,"journal":"Frontiers in neuroendocrinology, 77, 101175","doi":"10.1016/j.yfrne.2025.101175","pmid":"39892577","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10202","title":"Effects of tirzepatide on circulatory overload and end-organ damage in heart failure with preserved ejection fraction and obesity: a secondary analysis of the SUMMIT trial.","authors":"Borlaug, Barry A; Zile, Michael R; Kramer, Christopher M; Baum, Seth J; Hurt, Karla; Litwin, Sheldon E; Murakami, Masahiro; Ou, Yang; Upadhyay, Navneet; Packer, Milton","year":2025,"journal":"Nature medicine, 31(2), 544-551","doi":"10.1038/s41591-024-03374-z","pmid":"39551891","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10203","title":"Semaglutide and Exercise Function in Obesity-Related HFpEF: Insights From the STEP-HFpEF Program.","authors":"Borlaug, Barry A; Kitzman, Dalane W; Patel, Shachi; Chinnakondepalli, Khaja M; Butler, Javed; Davies, Melanie J; Petrie, Mark C; Shah, Sanjiv J; Verma, Subodh; Núñez, Julio; Einfeldt, Mette Nygaard; Liisberg, Karoline; Salsali, Afshin; Kosiborod, Mikhail N","year":2025,"journal":"JACC. Heart failure, 13(11), 102660","doi":"10.1016/j.jchf.2025.102660","pmid":"41045908","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10204","title":"Hypophagia and body weight loss by tirzepatide are accompanied by fewer GI adverse events compared to semaglutide in preclinical models.","authors":"Borner, Tito; Pataro, Allison M; Doebley, Sarah A; Furst, Charles D; White, Alex D; Gao, Serena X; Chow, Angela; Sanchez-Navarro, Marcos J; Ghidewon, Misgana Y; Halas, Julia G; Mohiby, Allaha Z; Willard, Francis S; Grill, Harvey J; Ai, Minrong; Samms, Ricardo J; Hayes, Matthew R; De Jonghe, Bart C","year":2025,"journal":"Science advances, 11(25), eadu1589","doi":"10.1126/sciadv.adu1589","pmid":"40532005","tags":[],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"GIPR activation has antiemetic properties that counteract the nausea and vomiting caused by GLP-1R activation. In rats and shrews, GIPR agonism blocked emesis and reduced malaise behaviors triggered by GLP-1R activation, while still maintaining the benefits of reduced food intake, weight loss, and improved glucose tolerance.\n\nAt equipotent doses for weight loss, tirzepatide (a dual GLP-1R/GIPR agonist) produced significantly fewer gastrointestinal side effects than semaglutide (a GLP-1R-only agonist). This explains why tirzepatide can achieve greater weight loss than semaglutide while patients report fewer GI complaints.","whyItMatters":"Nausea and vomiting are the most common reasons patients reduce their dose or stop GLP-1 drugs. This study reveals a key mechanistic insight: tirzepatide's GIP component actively suppresses the nausea caused by its GLP-1 component. This isn't just tolerance or dose-response — it's an intrinsic antiemetic effect that gives dual agonists a fundamental tolerability advantage.","specificNumbers":"Tirzepatide vs semaglutide at equipotent doses · Significantly fewer GI side effects · Maintained weight loss and glucose benefits · Rats and shrews tested · GIPR agonism blocks GLP-1R-induced emesis","methodology":"Preclinical study in rats (food intake, body weight, glucose tolerance) and shrews (emesis model — shrews can vomit, rats cannot). Tested GIPR agonism alone, GLP-1R agonism alone, and combined GLP-1R/GIPR agonism (tirzepatide) at equipotent weight-loss doses versus semaglutide. Assessed emesis episodes, malaise behaviors, food intake, body weight, and glucose tolerance.","limitations":"Animal study — GI tolerability in rodents and shrews may not perfectly translate to human experience. Shrews are used because rats cannot vomit, but the shrew emesis model has limitations. The study does not address long-term tolerability or chronic dosing patterns. Specific doses and effect sizes are not detailed in the abstract."},{"rthcId":"RPEP-10205","title":"From In Vitro Efficacy to Long-Term HbA1c Response for GLP-1R/GlucagonR Agonism Using the 4GI-HbA1c Systems Model.","authors":"Bosch, Rolien; Petrone, Marcella; Arends, Rosalin; Sijbrands, Eric J G; Hoefman, Sven; Snelder, Nelleke","year":2025,"journal":"CPT: pharmacometrics & systems pharmacology, 14(9), 1515-1525","doi":"10.1002/psp4.70074","pmid":"40665896","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The combined 4GI-HbA1c systems model successfully predicted the glucose and HbA1c-lowering effects of both liraglutide (a GLP-1 agonist) and cotadutide (a dual GLP-1/glucagon agonist) using only in vitro potency data and pharmacokinetic information. The model was validated against continuous glucose monitoring data from Phase 2a studies and achieved prediction errors of 5.9% for fasting plasma glucose and 13% for HbA1c.\n\nCritically, the model was used prospectively during cotadutide's clinical development to predict 26-week glucose and HbA1c outcomes of a Phase 2b study before the study was initiated — and retrospective analysis confirmed the predictions were adequate.","whyItMatters":"Developing peptide drugs is expensive and slow. This model allows pharmaceutical companies to predict how a new GLP-1 or dual agonist peptide drug will perform in clinical trials using only early-stage lab data, potentially saving years of development time and significant costs. The ability to forecast long-term HbA1c outcomes from in vitro potency data alone could accelerate the selection of the most promising peptide drug candidates before committing to large, expensive clinical trials.","specificNumbers":"RMSPE 5.9% for fasting glucose prediction · RMSPE 13% for HbA1c prediction · 26-week outcomes predicted prospectively · 2 peptide drugs validated (liraglutide, cotadutide) · Phase 2a CGM data used for calibration","methodology":"The researchers extended their previously developed 4GI glucose homeostasis systems model by coupling it with an existing integrated glucose-red blood cell-HbA1c (IGRH) model. The model translates in vitro potency and pharmacokinetic data into predicted 24-hour glucose profiles, then uses these to forecast HbA1c changes over time. Validation used continuous glucose monitoring data from Phase 2a clinical trials of liraglutide and cotadutide.","limitations":"The model was validated on only two peptide drugs (liraglutide and cotadutide), and broader validation across more GLP-1 agonists and dual agonists would strengthen confidence. The 13% prediction error for HbA1c is moderate and may not be sufficient for regulatory decision-making in all contexts. The model focuses on glucose control and does not predict other important outcomes like weight loss, cardiovascular effects, or safety profiles. Model calibration still required some clinical CGM data."},{"rthcId":"RPEP-10206","title":"Exploring the Antimicrobial and Antiviral Properties of Cryptic Peptides from Human Fibrinogen.","authors":"Bosso, Andrea; Masino, Antonio; Di Nardo, Ilaria; Zannella, Carla; Gaglione, Rosa; Palumbo, Ida; Culurciello, Rosanna; De Filippis, Anna; Torres, Marcelo D T; de la Fuente-Nunez, Cesar; Galdiero, Massimiliano; Arciello, Angela; Di Maro, Antimo; Pizzo, Elio; Cafaro, Valeria; Notomista, Eugenio","year":2025,"journal":"International journal of molecular sciences, 26(18)","doi":"10.3390/ijms26188914","pmid":"41009482","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10207","title":"Anesthesiologists' Perspectives on GLP-1 Receptor Agonists in Elective Surgeries: A Qualitative Survey Analysis of National Data.","authors":"Boudreau, Benjamin; Watson, Nicholas C","year":2025,"journal":"Cureus, 17(11), e95986","doi":"10.7759/cureus.95986","pmid":"41346889","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10208","title":"The pharmacokinetics and comparative bioavailabilty of oral and subcutaneous semaglutide in healthy volunteers.","authors":"Bouhajib, Mohammed; Tayab, Zia; Di Marco, Chantal; Suh, Dennis Dong-Kyun","year":2025,"journal":"Journal of basic and clinical physiology and pharmacology, 36(2-3), 221-227","doi":"10.1515/jbcpp-2025-0026","pmid":"40425315","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10209","title":"Abdominoplasty After Bariatric Surgery and GLP-1 Receptor Agonists: Independent vs Combined Complication Risks.","authors":"Boukind, Adam; He, Kevin; Speller, Nicholas; Badran, Saif","year":2025,"journal":"Aesthetic surgery journal","doi":"10.1093/asj/sjaf244","pmid":"41403207","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In propensity score-matched analyses of abdominoplasty patients:\n\n- GLP-1RA use independently increased hypertrophic scarring risk (RR=1.79, 95% CI 1.37-2.35), confirmed in sensitivity analysis against DPP-4 inhibitors (RR=2.40)\n- Prior bariatric surgery increased hematoma risk (RR=1.55, 95% CI 1.11-2.17) and seroma risk (RR=1.55, 95% CI 1.19-2.02), but lowered hypertrophic scarring (RR=0.74) and systemic infections (RR=0.78)\n- Combined BS + GLP-1RA use increased wound dehiscence risk (RR=1.92, 95% CI 1.12-3.38) and constitutional symptoms (RR=1.69, 95% CI 1.16-2.46)\n\nThe scarring finding with GLP-1RAs was robust across multiple analyses.","whyItMatters":"With millions of people now using GLP-1 receptor agonists for weight loss, and body contouring surgery demand surging, surgeons need to understand how these drugs affect surgical outcomes. The finding that GLP-1RAs significantly increase scarring risk — and that combining them with bariatric surgery worsens wound healing — has immediate implications for preoperative planning, patient counseling, and potentially the timing of drug discontinuation before surgery.","specificNumbers":"","methodology":"Retrospective cohort study using the TriNetX federated research network, including adults undergoing abdominoplasty from January 2004 to June 2025. Patients were categorized into four groups: no prior weight loss interventions, bariatric surgery only, recent GLP-1RA use only, and both. Propensity score matching controlled for confounders. Primary outcomes were 90-day postoperative complications. A sensitivity analysis compared GLP-1RA users to DPP-4 inhibitor users to isolate the GLP-1RA effect.","limitations":"This is a retrospective observational study, so it cannot establish causation. The TriNetX network may have coding biases affecting how complications are recorded. The mechanism by which GLP-1RAs increase scarring is unknown and may involve direct tissue effects, nutritional status changes, or other factors. The study could not determine whether discontinuing GLP-1RAs before surgery would mitigate risks. Specific GLP-1RA drugs and doses were not differentiated."},{"rthcId":"RPEP-10210","title":"Effect of Glucagon-like Peptide-1 Receptor Agonists on Outcomes After Hip Hemiarthroplasty for Femoral Neck Fractures in Patients With Type 2 Diabetes.","authors":"Box, McKenna W; Puga, Troy B; Werthmann, Neil J; Liu, Yingxian; Riehl, John T","year":2025,"journal":"Journal of the American Academy of Orthopaedic Surgeons. Global research & reviews, 9(10)","doi":null,"pmid":"41118557","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 499 diabetic patients undergoing hip hemiarthroplasty for femoral neck fractures, GLP-1RA use (n=248) was not associated with increased risk of any measured outcome compared to non-GLP-1RA users (n=251). Specifically, there was no increase in medical complications at 30, 90, or 365 days; no increase in surgical site infection, implant complications, or revision surgery; no increase in aspiration pneumonitis; and no difference in hospital length of stay or readmissions. GLP-1RA use was associated with decreased 365-day in-hospital mortality/hospice discharge. After controlling for confounders, no adverse outcome was associated with GLP-1RA use (all P>0.05).","whyItMatters":"As millions of patients take GLP-1 drugs, surgeons and anesthesiologists have worried about perioperative safety — particularly aspiration risk from delayed gastric emptying. This study provides real-world reassurance that GLP-1 drugs do not increase surgical complications in the high-risk setting of hip fracture surgery in elderly diabetic patients.","specificNumbers":"n=499 (248 GLP-1RA, 251 controls) · no increased medical complications at 30, 90, or 365 days · no increased implant complications · no increased aspiration · decreased 365-day mortality/hospice discharge · all adverse outcomes P>0.05 after adjustment","methodology":"Retrospective cross-sectional analysis of a hospital system database (2016–2023). Patients with T2DM aged 18+ who underwent hip hemiarthroplasty for femoral neck fractures were identified. GLP-1RA users (n=248) were compared to a 1:1 random matched sample of non-users (n=251). Elixhauser comorbidity index was recorded. Binary logistic regression assessed 30-day medical and 365-day implant outcomes.","limitations":"Single hospital system retrospective study with a relatively small sample. The 1:1 matching was random rather than propensity-based, which may leave residual confounding. The study could not determine specific GLP-1 agents or whether medications were held before surgery. Aspiration was measured as pneumonitis (clinical event) rather than subclinical aspiration."},{"rthcId":"RPEP-10211","title":"A New Kv1.3 Channel Blocker from the Venom of the Ant Tetramorium bicarinatum.","authors":"Boy, Guillaume; Jouvensal, Laurence; Téné, Nathan; Carayon, Jean-Luc; Bonnafé, Elsa; Paquet, Françoise; Treilhou, Michel; Loth, Karine; Billet, Arnaud","year":2025,"journal":"Toxins, 17(8)","doi":"10.3390/toxins17080379","pmid":"40864056","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10212","title":"Preclinical characterization of an active immunotherapy targeting calcitonin gene-related peptide.","authors":"Boyd, Justin D; Wang, Shixia; Lin, Hsiao-Wen; Hsieh, Yueh-Ting; Sun, Yu Shuang; Thibodeaux, Brett A; Lu, Hanxin; Sahni, Jaya; Wiggins, Jonathan; Longo, Matthew S; Brooks, Jeanne K; Vroom, Madeline M; Chang, Yi-Pin; Liu, Zhi; Ding, Shuang; Dodart, Jean-Cosme","year":2025,"journal":"Communications medicine, 5(1), 145","doi":"10.1038/s43856-025-00870-2","pmid":"40301574","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10213","title":"Solid Lipid Nanoparticles by Coacervation from Natural Soaps: Preliminary Studies for Oral Delivery of an Insulin Analogue.","authors":"Bozza, Annalisa; Marengo, Arianna; Blua, Federica; Marini, Elisabetta; Bagatella, Stefano; Ugazio, Elena; Muntoni, Elisabetta; Battaglia, Luigi","year":2025,"journal":"Pharmaceutics, 17(10)","doi":"10.3390/pharmaceutics17101261","pmid":"41155898","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10214","title":"Impact of Short-Term Liraglutide Therapy on Non-Invasive Markers of Liver Fibrosis in Patients with MASLD.","authors":"Bołdys, Aleksandra; Borówka, Maciej; Bułdak, Łukasz; Okopień, Bogusław","year":2025,"journal":"Metabolites, 15(8)","doi":"10.3390/metabo15080510","pmid":"40863129","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10215","title":"Liraglutide Reduces Liver Steatosis and Improves Metabolic Indices in Obese Patients Without Diabetes: A 3-Month Prospective Study.","authors":"Bołdys, Aleksandra; Bułdak, Łukasz; Nicze, Michał; Okopień, Bogusław","year":2025,"journal":"International journal of molecular sciences, 26(12)","doi":"10.3390/ijms26125883","pmid":"40565353","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10216","title":"Effectiveness and tolerability of liraglutide as add-on treatment in patients with obesity and high-frequency or chronic migraine: A prospective pilot study.","authors":"Braca, Simone; Russo, Cinzia Valeria; Stornaiuolo, Antonio; Cretella, Gennaro; Miele, Angelo; Giannini, Caterina; De Simone, Roberto","year":2025,"journal":"Headache, 65(10), 1831-1838","doi":"10.1111/head.14991","pmid":"40525593","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10217","title":"Semaglutide for adults living with obesity.","authors":"Bracchiglione, Javier; Meza, Nicolás; Franco, Juan Va; Escobar Liquitay, Camila Micaela; Novik A, Victoria; Ocara Vargas, Miranda; Lazcano, Gabriel; Poloni, Daniel; Rinaldi Langlotz, Francisca; Roqué-Figuls, Marta; Munoz, Sergio R; Madrid, Eva","year":2025,"journal":"The Cochrane database of systematic reviews, 10(10), CD015092","doi":"10.1002/14651858.CD015092.pub2","pmid":"41161683","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10218","title":"Comparative analysis on renal and cardiovascular outcomes of antidiabetic treatment in chronic kidney disease patients-A systematic review and network meta-analysis.","authors":"Bramlage, Peter; Vijayan, Anjaly; Varghese, Treesa P; Melepurakkal Sadanandan, Deepthy; Lanzinger, Stefanie; Rodriguez, Carmen Ferrero","year":2025,"journal":"Diabetes, obesity & metabolism, 27(11), 6254-6263","doi":"10.1111/dom.70010","pmid":"40798873","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 26 RCTs with 143,296 participants with T2DM and CKD:\n\n- SGLT2 inhibitors ranked highest (by P-score) for: composite renal events (0.94), eGFR decline >40% or renal replacement therapy (0.99), MACE (0.93), and heart failure (1.00)\n- GLP-1 RAs ranked highest for: myocardial infarction (0.87), macroalbuminuria (0.86), and stroke (0.83)\n- Both SGLT2 inhibitors and GLP-1 RAs had equal P-scores (0.83) for reducing all-cause mortality\n- DPP-4 inhibitors had limited benefits compared to either SGLT2 inhibitors or GLP-1 RAs across all outcomes","whyItMatters":"Diabetic kidney disease is one of the most dangerous metabolic complications, dramatically increasing cardiovascular and renal risks. Clinicians managing these complex patients need to know which drug class to prioritize. This meta-analysis provides the clearest comparative ranking to date, showing that the two drug classes have complementary strengths — supporting the clinical strategy of using SGLT2 inhibitors for renal and heart failure protection while adding GLP-1 peptide agonists for atherosclerotic cardiovascular risk reduction.","specificNumbers":"","methodology":"Systematic review and network meta-analysis of randomized controlled trials published between 2014-2024, identified through PubMed, Scopus, and clinical trial registries. Twenty-six studies with 143,296 participants with T2DM and CKD were included. Drug classes compared: SGLT2 inhibitors, GLP-1 receptor agonists, and DPP-4 inhibitors. P-scores were used to rank treatments for each outcome (higher = better).","limitations":"Network meta-analysis relies on indirect comparisons when head-to-head trials are unavailable. The analysis aggregates different drugs within each class (e.g., multiple SGLT2 inhibitors), potentially masking within-class differences. CKD staging and severity varied across included trials. The time period (2014-2024) means the newest GLP-1 agonist data (high-dose semaglutide) and tirzepatide CKD data may not be fully captured. P-scores provide rankings but not absolute effect sizes for comparison."},{"rthcId":"RPEP-10219","title":"Naltrexone/Bupropion, Liraglutide, or Semaglutide as Adjuvant Therapy After Metabolic and Bariatric Surgery: An Observational Study.","authors":"Brancatisano, Anthony; Ryan, Brendan","year":2025,"journal":"Obesity science & practice, 11(6), e70097","doi":"10.1002/osp4.70097","pmid":"41234488","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 121 patients who had regained weight (median 9.7 kg, or 27.9% of total weight previously lost) or had suboptimal weight loss after bariatric surgery, adjuvant obesity medications produced a median 8.8% total body weight loss (IQR 5.7-14.1%) over a median follow-up of 9 months.\n\nSemaglutide was the most commonly prescribed (52.8% of patients), followed by naltrexone/bupropion (28.1%) and liraglutide (19.1%). The medications were effective across all surgery types: sleeve gastrectomy (59.7%), one-anastomosis gastric bypass (11.8%), adjustable gastric banding (6.7%), and conversional procedures (21.8%). Adverse effects were minor and consistent with those seen in non-surgical clinical trial populations.","whyItMatters":"Weight regain after bariatric surgery is common — affecting 20-30% of patients — and has been one of the most frustrating challenges in obesity medicine. Previously, the options were limited to revision surgery or lifestyle counseling. This study provides real-world evidence that GLP-1 receptor agonists and other obesity medications can serve as effective 'rescue' therapy, supporting the growing consensus that obesity is a chronic disease requiring ongoing management even after surgery.","specificNumbers":"","methodology":"This was a single-center observational study of 121 patients prescribed obesity management medications for recurrent weight gain or suboptimal weight loss following primary or conversional bariatric surgery. Patients received either naltrexone/bupropion extended-release (8/90 mg), liraglutide (3.0 mg), or semaglutide (1.0 mg). Data were analyzed using parametric and nonparametric statistics with results reported as median with interquartile ranges.","limitations":"This is an observational study without a control group, so the weight loss cannot be definitively attributed to the medications versus other factors. The three medications were not compared head-to-head with equal group sizes (semaglutide was prescribed to over half the patients). The semaglutide dose used (1.0 mg) is the diabetes dose, not the higher 2.4 mg dose approved for obesity. Follow-up was relatively short (median 9 months). Patient selection for each medication was not randomized, introducing potential selection bias."},{"rthcId":"RPEP-10220","title":"Semaglutide reverses the chronic myopathy of hyperkalemic periodic paralysis: a case report.","authors":"Brand, Kenneth; Landry, Daniel; Mulhern, Jeffrey; Braden, Gregory","year":2025,"journal":"BMC nephrology, 26(1), 179","doi":"10.1186/s12882-025-04068-5","pmid":"40197299","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A 48-year-old man with hyperkalemic periodic paralysis (hyperPP) caused by a SCN4A sodium channel mutation experienced dramatic reversal of chronic myopathy after starting semaglutide for weight loss. Before treatment, he could not rise from a chair without help and had a very slow gait. Over the following year, his strength and quality of life returned to levels he hadn't experienced in decades. Previous treatments with acetazolamide and diclofenamide had been ineffective. The authors propose semaglutide acts on skeletal muscle through both insulin-dependent and insulin-independent mechanisms.","whyItMatters":"This case report reveals an unexpected therapeutic application of semaglutide — reversing chronic muscle weakness in a genetic muscle disorder. HyperPP has limited treatment options, and existing drugs have had poor success. The finding that a GLP-1 peptide drug can directly improve skeletal muscle function suggests semaglutide may have important effects on muscle biology beyond its known metabolic benefits, potentially opening a new treatment avenue for muscle disorders.","specificNumbers":"n=1 · 48-year-old male · SCN4A gene mutation at position 704 (Thr→Met) · symptoms since childhood · permanent weakness since age 30 · semaglutide initiated spring 2023 · strength improvement over 1 year · could not rise from chair before treatment","methodology":"This is a single case report describing the clinical observation of muscle function improvement in a patient with genetically confirmed hyperkalemic periodic paralysis who started semaglutide for weight management. The improvement was assessed clinically through functional capacity (ability to rise from a chair, gait quality) and patient-reported quality of life.","limitations":"As a single case report, causal attribution is uncertain — the improvement could potentially be related to weight loss effects or other factors rather than direct semaglutide effects on muscle. There is no controlled comparison or objective muscle testing data (e.g., electromyography, muscle biopsy, or quantitative strength measurements). The mechanism of action on skeletal muscle is proposed but not experimentally validated in this report."},{"rthcId":"RPEP-10221","title":"The Effect of Semaglutide With Lifestyle Intervention on the Physical Health of Patients Treated With Antipsychotic Drugs in a Secure Mental Health Setting: Protocol for an Uncontrolled Pretest-Posttest Pilot Mixed Methods Study.","authors":"Brenisin, Kristina; Kinnafick, Florence; King, James; Millard, Louise; Arya, Donna; Hodgson, Elizabeth; Huggins, Michelle; Simmons-Roberts, Andrew; O'Dowd, Martin; Rayment, Nick; Shah, Parul; Breen, Kieran C","year":2025,"journal":"JMIR research protocols, 14, e76013","doi":"10.2196/76013","pmid":"41364787","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10222","title":"Will GLP-1 Agonists Weaken the Links between Obesity and Cancer?","authors":"Brennan, Donal J; Lynch, Lydia","year":2025,"journal":"Cancer discovery, 15(11), 2209-2212","doi":"10.1158/2159-8290.CD-25-0991","pmid":"41178350","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10223","title":"Lanifibranor and semaglutide demonstrate multiple metabolic benefits in free-choice diet induced obese hamster models of MASH and MetALD.","authors":"Briand, François; Dubroca, Caroline; Wettstein, Guillaume; Grasset, Estelle; Breyner, Natalia; Bigot, Claire; Assaly, Rana; Broqua, Pierre; Sulpice, Thierry","year":2025,"journal":"European journal of pharmacology, 1003, 177945","doi":"10.1016/j.ejphar.2025.177945","pmid":"40653077","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In free-choice diet obese hamsters with MASH and heart failure:\n\nSemaglutide effects:\n- Transiently reduced food intake\n- Significantly reduced fructose and alcohol consumption\n- Significant body weight loss\n- Lower HOMA-IR index (improved insulin resistance)\n- Improved dyslipidemia (cholesterol problems)\n- Improved heart failure with preserved ejection fraction (HFpEF)\n- Reduced hepatic fat content only (not full MASH resolution)\n\nLanifibranor showed similar cardiometabolic benefits but was superior in the liver, significantly improving both MASH and alcohol-related liver disease (MetALD).\n\nBoth drugs' effects in hamsters matched what has been observed in human clinical trials, validating the animal model.","whyItMatters":"Semaglutide is already one of the most prescribed GLP-1 drugs worldwide. This study expands understanding of its benefits beyond weight loss and diabetes to liver disease and heart failure — two of the most serious consequences of obesity. The finding that semaglutide reduces voluntary alcohol consumption is particularly intriguing, as it aligns with emerging human reports of reduced cravings for alcohol and addictive substances on GLP-1 drugs.","specificNumbers":"","methodology":"Obese hamsters were created using a free-choice diet model that produces human-like lipoprotein metabolism, MASH, and heart failure with preserved ejection fraction. Animals were treated with semaglutide or lanifibranor. Some hamsters were also exposed to ethanol to model chronic alcohol intake and alcohol binge drinking (MetALD model). Metabolic parameters, liver histology, cardiac function, and voluntary consumption behaviors were measured.","limitations":"This is an animal study using hamsters, which are chosen for their human-like lipoprotein metabolism but don't perfectly replicate human disease. Dosing and treatment durations in hamsters may not translate directly to humans. Semaglutide reduced liver fat but did not fully resolve MASH, suggesting it may not be sufficient as a standalone liver therapy. The alcohol consumption effects were observed in animals and may not predict human behavior changes."},{"rthcId":"RPEP-10224","title":"Enzymatic bromination of native peptides for late-stage structural diversification via Suzuki-Miyaura coupling.","authors":"Bridge, Haley N; Radziej, Chase L; Weeks, Amy M","year":2025,"journal":"bioRxiv : the preprint server for biology","doi":"10.64898/2025.12.17.694899","pmid":"41446194","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10225","title":"Successful Treatment of Hypothalamic Obesity with Tirzepatide.","authors":"Brijmohan, Sharmela; Mullally, Jamie A","year":2025,"journal":"AACE endocrinology and diabetes, 12(1), 30-33","doi":"10.1016/j.aed.2025.03.004","pmid":"40677794","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10226","title":"Engineered probiotic restores GLP-1 signaling to ameliorate fiber-deficiency exacerbated colitis.","authors":"Brockmann, Leonie; Ronda, Carlotta; Schwanz, Logan T; Qu, Yiming; Shneider, Daniel W; Mavros, Chrystal F; Ivanov, Ivaylo I; Bhagat, Govind; Wang, Harris H","year":2025,"journal":"Science advances, 11(45), eadx6869","doi":"10.1126/sciadv.adx6869","pmid":"41202140","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10227","title":"Potential Therapeutic Role of GLP-1 Receptor Agonists in the Management of Opioid Use Disorders: A Literature Review.","authors":"Bronson, Skylar; Groves, Kyla; Noorani, Seham; Boothe, Danielle; Gopal, Medha; Quinonez, Jonathan","year":2025,"journal":"Addiction & health, 17, 1682","doi":"10.34172/ahj.1682","pmid":"41431626","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10228","title":"Acute Mesenteric Ischemia as a Severe Complication Associated With Tirzepatide: A Case Report and Safety Alert.","authors":"Brooks, Shani; Nafees, Samraiz; Abdi, Khaled; Austin, Isobel; Mahmood, Balal; Bowden, Adam; Warren, Emily; Crossley, Alexander; Mehmood, Azhar; Birkett, Victoria","year":2025,"journal":"Cureus, 17(11), e97035","doi":"10.7759/cureus.97035","pmid":"41416326","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A case of acute mesenteric ischemia (loss of blood flow to the intestines) occurred in a patient taking tirzepatide, a dual GIP/GLP-1 receptor agonist used for type 2 diabetes. The authors propose this rare but serious adverse event may be related to tirzepatide's effects on gastrointestinal motility and vascular perfusion. The case report serves as a safety alert highlighting the need for careful patient selection and close monitoring, particularly as tirzepatide use expands outside formal clinical supervision.","whyItMatters":"Acute mesenteric ischemia is a life-threatening surgical emergency with high mortality rates. As tirzepatide becomes one of the most widely prescribed medications for diabetes and obesity, identifying rare but serious complications is critical. This case report raises the possibility that GLP-1/GIP receptor agonists may affect intestinal blood flow — a mechanism not widely discussed in the safety profile of these drugs.","specificNumbers":"","methodology":"Single-patient case report documenting acute mesenteric ischemia following tirzepatide treatment. The authors describe the clinical presentation, diagnosis, and proposed mechanism linking tirzepatide's effects on gastrointestinal motility and vascular perfusion to the adverse event.","limitations":"This is a single case report, which cannot establish causation between tirzepatide and mesenteric ischemia. The patient may have had other risk factors for vascular disease. Without denominator data (how many patients take tirzepatide without this complication), the absolute risk cannot be estimated. The proposed mechanism linking GLP-1/GIP agonism to mesenteric ischemia is speculative and requires further investigation."},{"rthcId":"RPEP-10229","title":"Diet strategies for maintaining substantial therapeutic weight loss: 78-week mixed methods randomised trial.","authors":"Brosnahan, Naomi; Hankey, Catherine; Leeds, Anthony; Leslie, Wilma; Thom, George; Hutchison, Lisa; Govan, Lindsay; Ross, Hazel; Lean, Michael E J","year":2025,"journal":"Clinical nutrition (Edinburgh, Scotland), 53, 188-198","doi":"10.1016/j.clnu.2025.08.009","pmid":"40934815","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10230","title":"Great Debates: Undergoing the Knife versus Pill-Popping-The Comparative Efficacy and Cost-Effectiveness of Bariatric Surgery and GLP-1 Receptor Agonists in the Management of Obesity.","authors":"Brosnihan, Paul; Luce, M Siobhan; Yetasook, Amy K; Perez, Christian; Scharf, Keith R; Aly, Sherif","year":2025,"journal":"The American surgeon, 91(10), 1587-1593","doi":"10.1177/00031348251337145","pmid":"40285863","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10231","title":"Aging reveals divergent responses of AgRP/NPY neurons to diet in male and female mice.","authors":"Brothers, Tionna; Wei, Wei; Korgan, Austin C; Bridges, Zoey; O'Connell, Kristen M S","year":2025,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2025.11.20.689576","pmid":"41332702","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10232","title":"Potential health benefits of lactoferrin and derived peptides - how to qualify as a medical device?","authors":"Brouwer, Carlo; Welling, Mick M; Alwasel, Saleh; Boekhout, Teun","year":2025,"journal":"Critical reviews in microbiology, 51(6), 1041-1065","doi":"10.1080/1040841X.2025.2466465","pmid":"39964125","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10233","title":"Sleeve-to-bypass conversion vs. sleeve-with-adjuvant GLP-1 receptor agonists: an academic multicenter retrospective study.","authors":"Brown, Avery; Sergent, Helena; Vu, Alexander Hien; Liu, Helen; Fisher, Jason; Somoza, Eduardo; Mei, Tony; Lipman, Jeffrey; Park, Julia; Chui, Patricia; Saunders, John; Kurian, Marina; Tchokouani, Loic; Orandi, Babak; Ferzli, George; Chhabra, Karan; Ren-Fielding, Christine; Parikh, Manish; Jenkins, Megan","year":2025,"journal":"Surgical endoscopy, 39(9), 6155-6162","doi":"10.1007/s00464-025-11942-8","pmid":"40691334","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 4,901 patients (3,004 conversion RYGB, 1,897 GLP-1 RA) with prior sleeve gastrectomy, pre-intervention weights were identical between groups (242.8 vs. 242.3 lbs, p=0.993). In multivariate analysis adjusting for sex, baseline BMI, age, and race, conversion to RYGB was associated with 11% greater percentage total body weight loss compared to GLP-1 RA treatment at 3 years. Both groups showed similar improvements in HbA1c at all time points (p>0.05). The cRYGB group had higher baseline HbA1c (6.19 vs. 5.85, p significant).","whyItMatters":"As GLP-1 drugs become widely available, more patients are considering them as an alternative to revision surgery after failed bariatric procedures. This is one of the largest studies directly comparing these two approaches, providing data that helps patients and surgeons make informed decisions. The 11% weight loss difference is clinically meaningful but must be weighed against the risks and costs of a second surgery.","specificNumbers":"","methodology":"This was a multicenter academic retrospective study including adult patients (≥18 years) who previously had sleeve gastrectomy and were subsequently treated with weekly injectable semaglutide or tirzepatide, or underwent conversion to Roux-en-Y gastric bypass. Patients converted for GERD, those with BMI ≤35 on GLP-1 RA, or with pre-operative GLP-1 RA use were excluded. Weight and HbA1c were assessed from 3 months to 3 years. T-test, ANOVA, chi-squared, and multivariable linear regression analyses were used.","limitations":"This is a retrospective study, making it susceptible to selection bias — patients offered GLP-1 drugs vs. revision surgery may differ in ways not captured by baseline characteristics. GLP-1 RA adherence and duration of use were not tracked. The study did not assess quality of life, complications, or patient satisfaction. Semaglutide and tirzepatide were analyzed together despite different mechanisms."},{"rthcId":"RPEP-10234","title":"Liraglutide and Weight Loss Among Suboptimal Responders to Metabolic Bariatric Surgery: A Randomized Clinical Trial.","authors":"Brown, Wendy A; Burton, Paul R; Laurie, Cheryl; Paul, Eldho; Johari, Yazmin; Cowley, Michael A; Wentworth, John","year":2025,"journal":"JAMA network open, 8(10), e2539848","doi":"10.1001/jamanetworkopen.2025.39848","pmid":"41160027","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10235","title":"Weight Loss in Veterans with Schizophrenia and Multimorbidity Prescribed Semaglutide: Results From a National Retrospective Cohort Study.","authors":"Browne, Julia; Wu, Wen-Chih; Jiang, Lan; Bayer, Thomas A; Kunicki, Zachary J; Thompson, Matthew; Bozzay, Melanie L; De Vito, Alyssa N; Howe, Matthew D; Singh, Mriganka; Primack, Jennifer M; McGeary, John E; Maharaj, Ritesh; Kelso, Catherine M; Philip, Noah S; Greenberg, Benjamin D; Rudolph, James L","year":2025,"journal":"Schizophrenia bulletin","doi":"10.1093/schbul/sbaf143","pmid":"40819269","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10236","title":"Safety and efficacy of 24 weeks of pemvidutide in metabolic dysfunction-associated steatotic liver disease: A randomized, controlled clinical trial.","authors":"Browne, Sarah K; Suschak, John J; Tomah, Shaheen; Gutierrez, Julio A; Yang, Jay; Georges, Bertrand; Roberts, M Scot; Harris, M Scott","year":2025,"journal":"JHEP reports : innovation in hepatology, 7(11), 101483","doi":"10.1016/j.jhepr.2025.101483","pmid":"41113119","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10237","title":"The physiologic and psychologic effects of glucagon-like peptide-1 receptor agonists.","authors":"Browne-Bradwisch, Sarah A; Smith, Erin Murphy; Wilson-Mooney, Catherine; Donahue-Stathis, Courtney","year":2025,"journal":"Nursing, 55(9), 48-54","doi":"10.1097/NSG.0000000000000223","pmid":"40851184","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 receptor agonists are FDA-approved for type 2 diabetes and cardiovascular risk reduction, with beneficial effects extending to obesity and related conditions. The article discusses both the physiologic mechanisms and the psychological effects of these medications, providing a clinical overview of their safety and effectiveness profile.","whyItMatters":"As GLP-1 receptor agonists become among the most widely prescribed medications worldwide, understanding both their physical and psychological effects is critical for healthcare providers and patients. This review addresses the dual nature of these drugs — their metabolic benefits alongside their mental health impacts — which is increasingly relevant as prescriptions expand beyond diabetes to obesity management.","specificNumbers":"","methodology":"This is a narrative review article published in a nursing journal, synthesizing current evidence on the safety and effectiveness of GLP-1 receptor agonists for type 2 diabetes, obesity, and related conditions, with attention to both physiologic and psychologic outcomes.","limitations":"As a narrative review in a clinical nursing journal, this article does not present original data or follow systematic review methodology. The abstract provides limited detail on the specific psychologic effects discussed in the full article."},{"rthcId":"RPEP-10238","title":"Oral Semaglutide as an Opportunity for an Appropriate Therapeutic Switch in People with Type 2 Diabetes: A Delphi Consensus.","authors":"Bruglia, Matteo; Cardini, Francesca; Di Luzio, Raffaella; Fiorini, Stefania; Guberti, Antonella; Haddoub, Silvia; Preiato, Valentina Lo; Luberto, Alessandra; Lugli, Francesca; Maiello, Massimiliano; Manicardi, Elisa; Marcellini, Marco Marcello; Monesi, Marcello; Pellicano, Francesca; Piani, Daniela; Trianni, Rosa Maria; Vacirca, Anna; Nicolucci, Antonio; Di Bartolo, Paolo","year":2025,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 16(8), 1707-1725","doi":"10.1007/s13300-025-01762-3","pmid":"40542226","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10239","title":"NRPS-like Gene LYS2 Contributed to the Biosynthesis of Cyclo(Pro-Val) in a Multistress-Tolerant Aromatic Probiotic, Meyerozyma guilliermondii GXDK6.","authors":"Bu, Ru; Li, Zhenze; Qin, Qiyu; Bai, Huashan; Meng, Can; Wei, Ruihang; Chen, Xinglin; Wu, Shanguang; Kashif, Muhammad; He, Sheng; Jiang, Chengjian","year":2025,"journal":"Journal of agricultural and food chemistry, 73(1), 507-520","doi":"10.1021/acs.jafc.4c08573","pmid":"39699118","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The NRPS-like gene LYS2 (3,825 bp, encoding 1,274 amino acids) was identified as essential for cyclo(Pro-Val) biosynthesis in the marine probiotic yeast M. guilliermondii GXDK6. The encoded enzyme (Lys2p, an L-2-amino-hexanedioic acid reductase) utilizes a novel macrocyclization mechanism involving peptide N-terminal and C-terminal imines through nucleophilic reactions.\n\nOverexpressing LYS2 increased cyclo(Pro-Val) production by 45.5%, while knocking out LYS2 completely eliminated synthesis — confirming it as the essential biosynthetic gene. This establishes a new metabolic regulatory pathway for cyclic peptide production in yeast.","whyItMatters":"Cyclic peptides (diketopiperazines) are increasingly recognized for their bioactive properties, but efficient production methods have been lacking. By identifying the exact gene and mechanism responsible for cyclic peptide biosynthesis in a probiotic yeast, this study opens the door to scalable biotechnological production. Using a probiotic organism as the production platform adds potential food-safety advantages. The 45.5% production increase from a single gene overexpression demonstrates practical engineering potential.","specificNumbers":"","methodology":"The marine probiotic yeast M. guilliermondii GXDK6 was used as the chassis organism. The LYS2 gene was identified through genomic analysis and functionally characterized using overexpression and knockout experiments. Cyclo(Pro-Val) production was quantified under both conditions. The macrocyclization mechanism was characterized at the molecular level, revealing the novel imine-mediated nucleophilic reaction pathway.","limitations":"The study focuses on a single cyclic dipeptide (cyclo(Pro-Val)) in a single yeast strain. Whether LYS2 can be leveraged to produce other diketopiperazines or more complex cyclic peptides is unknown. The 45.5% increase in production, while significant, may not be sufficient for commercial-scale manufacturing without further optimization. The bioactivities of cyclo(Pro-Val) mentioned are referenced but not experimentally validated in this study. Scale-up from laboratory to industrial production was not demonstrated."},{"rthcId":"RPEP-10240","title":"Acupuncture and the HPO Axis: A Review of Neuroendocrine Mechanisms With Implications for Ovarian Function.","authors":"Bu, Yu; Yan, Jinglan; Zhang, Zhen; Xue, Song; Chi, Funa; Zheng, Yuanjia; Xia, Yucen; Chen, Yongjun","year":2025,"journal":"Journal of integrative neuroscience, 24(10), 39451","doi":"10.31083/JIN39451","pmid":"41200977","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10241","title":"Novel oral agents in anti-obesity pharmacotherapy: A narrative review.","authors":"Buch, Assaf; Eldor, Roy; Brown, Roy; Zonszein, Joel","year":2025,"journal":"Diabetes, obesity & metabolism, 27(10), 5409-5417","doi":"10.1111/dom.16618","pmid":"40662383","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10242","title":"Efficacy and safety of danuglipron (PF-06882961) in adults with obesity: A randomized, placebo-controlled, dose-ranging phase 2b study.","authors":"Buckeridge, Clare; Cobain, Sonia; Bays, Harold E; Matsuoka, Osamu; Fukushima, Yasushi; Halstead, Patricia; Tsamandouras, Nikolaos; Sherry, Nicole; Gorman, Donal N; Saxena, Aditi R","year":2025,"journal":"Diabetes, obesity & metabolism, 27(9), 4915-4926","doi":"10.1111/dom.16534","pmid":"40539310","tags":["glp-1"],"studyType":"rct","evidenceStrength":"strong","keyFinding":"Pfizer's oral GLP-1 drug danuglipron produced statistically significant weight loss in adults with obesity — ranging from 5.0% to 12.9% beyond placebo depending on dose — over 26 to 32 weeks. However, the trial was marred by very high dropout rates: only 39.3% of participants completed treatment, with approximately 38% discontinuing due to adverse events (primarily nausea and vomiting).\n\nThe weight loss was dose-dependent, with higher doses producing more weight loss but also more GI side effects. The drug was given twice daily at doses from 40 to 200 mg, escalated over 1, 2, or 4 weeks. While the efficacy signal was clear, the tolerability problem was worse than expected across all treatment groups.","whyItMatters":"The GLP-1 weight-loss market is dominated by injectable drugs like semaglutide and tirzepatide. An effective oral GLP-1 pill could dramatically expand access — no injections, no refrigeration, easier to prescribe. Danuglipron showed the efficacy is there (up to 12.9% weight loss beyond placebo), but the 38% dropout rate from side effects is a major red flag. This tolerability challenge is the central obstacle Pfizer must solve to compete in the oral GLP-1 space.","specificNumbers":"n=628 · 536 danuglipron + 90 placebo · Weight loss: -5.0% to -12.9% vs placebo · 39.3% completed treatment · ~38% discontinued for AEs · 40–200 mg BID · 26–32 weeks","methodology":"Randomized, double-blind, placebo-controlled Phase 2b dose-ranging study. 628 adults (ages 18–75) with obesity but without diabetes were randomized to various danuglipron doses (40–200 mg twice daily) or placebo for 26 or 32 weeks. Doses were escalated over 1, 2, or 4 weeks. Primary endpoint was percentage change in body weight from baseline.","limitations":"The 60.7% discontinuation rate (38% from adverse events alone) severely undermines the reliability of efficacy estimates — participants who tolerated the drug may not represent the broader patient population. Twice-daily dosing is a compliance burden compared to once-weekly injectable competitors. The study excluded people with diabetes, so results may differ in diabetic populations. The 26–32 week duration is relatively short for a weight-loss drug intended for long-term use."},{"rthcId":"RPEP-10243","title":"Early worsening of diabetic retinopathy in individuals with type 2 diabetes treated with tirzepatide: a real-world cohort study.","authors":"Buckley, Adam J; Tan, Garry D; Gruszka-Goh, Marta; Scanlon, Peter H; Ansari, Imran; Suliman, Sara G I","year":2025,"journal":"Diabetologia, 68(9), 2069-2076","doi":"10.1007/s00125-025-06466-8","pmid":"40637847","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10244","title":"Developing Potent and Selective Anticancer Therapy through Chemical Approaches and the Combination of Cationic Amphipathic Oncolytic Peptides.","authors":"Bui Thi Phuong, Hai; Nguyen, Bao Loc; Huang, Linyu; Nguyen, Thi Oanh Oanh; Le, Ngoc Duy; Kim, Beomsu; Patil, Basavaraj Rudragouda; Nguyen Quoc, Thang; Kim, Jeonghwan; Luong, Huy Xuan; Kim, And Jong Oh","year":2025,"journal":"Journal of medicinal chemistry, 68(11), 11875-11893","doi":"10.1021/acs.jmedchem.5c00699","pmid":"40446125","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10245","title":"Effects of Blood-Glucose Lowering Therapies on Body Composition and Muscle Outcomes in Type 2 Diabetes: A Narrative Review.","authors":"Bujdei-Tebeică, Ioana; Mihai, Doina Andrada; Pantea-Stoian, Anca Mihaela; Ștefan, Simona Diana; Stoicescu, Claudiu; Serafinceanu, Cristian","year":2025,"journal":"Medicina (Kaunas, Lithuania), 61(8)","doi":"10.3390/medicina61081399","pmid":"40870444","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10246","title":"The potential role of GLP-1 receptor agonists in the management of psoriatic disease: a scoping review.","authors":"Buonanno, Simona; Gaggiano, Carla; Terribili, Riccardo; Cantarini, Luca; Frediani, Bruno; Gentileschi, Stefano","year":2025,"journal":"Inflammation research : official journal of the European Histamine Research Society ... [et al.], 74(1), 167","doi":"10.1007/s00011-025-02140-2","pmid":"41266905","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10247","title":"cAmbly: A non-toxic cell-penetrating peptide derived from Amblyomin-X with targeted delivery to mitochondrial and cytoplasmic proteins.","authors":"Buri, Marcus Vinicius; Garavelli, Graciana Yokota; Vigerelli, Hugo; de Souza, Marcelo Medina; Maia Lobba, Aline Ramos; Ghidelli-Disse, Sonja; Chudzinski-Tavassi, Ana Marisa","year":2025,"journal":"PloS one, 20(3), e0318119","doi":"10.1371/journal.pone.0318119","pmid":"40072951","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10248","title":"Dermatologic Implications of Glucagon-Like Peptide-1 Receptor Agonist Medications.","authors":"Burke, Olivia M; Sa, Brianna; Cespedes, David Alvarez; Tosti, Antonella","year":2025,"journal":"Skin appendage disorders, 11(5), 416-423","doi":"10.1159/000544023","pmid":"41058954","tags":["glp-1","safety"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"GLP-1 receptor agonists are associated with a range of dermatologic effects — some harmful, some potentially beneficial. On the adverse side: injection-site reactions, immune-mediated responses including hypersensitivity, urticaria, and bullous pemphigoid (a blistering skin condition), facial fat loss dubbed \"Ozempic face,\" and hair loss in the form of telogen effluvium linked to rapid weight loss.\n\nOn the potentially positive side, emerging evidence suggests GLP-1 drugs may enhance wound healing and could benefit inflammatory skin conditions like psoriasis. The review highlights that as GLP-1 use expands to millions of patients, dermatologic side effects are becoming an increasingly important clinical consideration.","whyItMatters":"As GLP-1 drugs move from niche diabetes treatments to mainstream weight loss medications used by millions, their skin-related side effects are becoming impossible to ignore. \"Ozempic face\" has become a cultural phenomenon, and hair loss is a frequently reported concern. At the same time, the anti-inflammatory properties of GLP-1 drugs raise intriguing possibilities for conditions like psoriasis. Dermatologists are increasingly seeing patients on these drugs and need to understand the full spectrum of skin effects.","specificNumbers":"","methodology":"Narrative review of published literature on the dermatologic effects of GLP-1 receptor agonists, including case reports, clinical trials, and post-marketing surveillance data on skin-related adverse events and potential therapeutic benefits.","limitations":"This is a narrative review, not a systematic review with quantified effect sizes. Many of the reported dermatologic effects come from case reports or small series rather than controlled studies. The causal relationship between GLP-1 drugs and some skin effects (like hair loss) may be confounded by the rapid weight loss itself rather than the drug directly."},{"rthcId":"RPEP-10249","title":"Exploring the Potential Dermatological Benefits of CGRP Inhibition: A Case Report.","authors":"Burke, Olivia M; Cocores, Alexandra; Beer, Jacob; Keri, Jonette E","year":2025,"journal":"Journal of drugs in dermatology : JDD, 24(6), 636-637","doi":"10.36849/JDD.8880","pmid":"40465494","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A 30-year-old woman with treatment-resistant cystic acne and PCOS experienced near-complete clearance of her cystic acne within 4 weeks of starting rimegepant (a CGRP receptor antagonist) for migraine management. Key details:\n\n- Previous failed treatments: antibiotics and hormonal therapy\n- Most affected area (chin) cleared almost entirely\n- Both cosmetic and physical discomfort (painful lesions) resolved\n- Acne did not recur, except for a minor episode during high stress\n- The improvement was an unexpected secondary benefit of migraine treatment\n\nThe proposed mechanism involves CGRP's role in neurogenic inflammation and its effects on sebaceous gland activity, both of which contribute to acne pathology.","whyItMatters":"Cystic acne affects millions of people and can be extremely difficult to treat — particularly when it resists standard therapies like antibiotics and hormonal treatments. This case suggests that CGRP, a neuropeptide already targeted by FDA-approved migraine drugs, may be a viable target for acne treatment. If confirmed in larger studies, CGRP antagonists could offer a new therapeutic option for patients with inflammatory skin conditions who have exhausted current treatments.","specificNumbers":"","methodology":"Single case report documenting the clinical course of a patient who incidentally experienced acne improvement while taking rimegepant for migraine. The patient's treatment history, timeline of improvement, and subsequent course were documented.","limitations":"This is a single case report — the weakest form of clinical evidence. The improvement could be coincidental or related to other factors. No control group, blinding, or objective acne scoring was used. The patient had PCOS, which complicates the acne picture. Stress-related minor recurrence suggests the underlying condition was not fully resolved. One case cannot establish CGRP inhibition as an acne treatment."},{"rthcId":"RPEP-10250","title":"The use of tirzepatide to successfully treat persistent genital arousal disorder/genitopelvic dysesthesia: a case report.","authors":"Burr, Eliza; Roytman, Maya; Poirier, Évéline; Kolbuszewska, Marta; Pfaus, James G; Komisaruk, Barry R; Goldstein, Irwin; Rubin, Rachel","year":2025,"journal":"Sexual medicine, 13(4), qfaf073","doi":"10.1093/sexmed/qfaf073","pmid":"41001580","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10251","title":"Immunoregulatory and antiviral effect mediated by TLR7 and BMAP28 interaction in bovine alphaherpesvirus-infected respiratory primary cultures.","authors":"Burucúa, Mercedes M; Risalde, María A; Langellotti, Cecilia A; Quintana, Silvina; Odeón, Anselmo C; Cobo, Eduardo R; Cutrera, Ana Paula; Pérez, Sandra E; Marin, Maia S","year":2025,"journal":"Veterinary microbiology, 300, 110342","doi":"10.1016/j.vetmic.2024.110342","pmid":"39705819","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10252","title":"Durable insulin elimination after duodenal re-cellularization via electroporation therapy combined with glucagon-like peptide-1 receptor agonist in patients with type 2 diabetes.","authors":"Busch, Celine B E; van den Hoek, Kim; van Baar, Annieke C G; Meiring, Suzanne; Bouwmeester, Thomas A; Holleman, Frits; Nieuwdorp, Max; Bergman, Jacques J G H M","year":2025,"journal":"iGIE : innovation, investigation and insights, 4(2), 120-128.e1","doi":"10.1016/j.igie.2025.03.012","pmid":"41646459","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10253","title":"Long-term effects of duodenal mucosal resurfacing and liraglutide on glycaemic control in patients with type 2 diabetes.","authors":"Busch, Celine B E; Rubingh, Julia; van Baar, Annieke C G; Nieuwdorp, Max; Bergman, Jacques J G H M","year":2025,"journal":"BMJ nutrition, prevention & health, 8(1), e001006","doi":"10.1136/bmjnph-2024-001006","pmid":"40771521","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10254","title":"Long-term comparative effectiveness of once-weekly semaglutide versus alternative treatments in a real-world US adult population with type 2 diabetes: a randomized pragmatic clinical trial.","authors":"Buse, John B; Nordahl Christensen, Helene; Harty, Brian J; Cziraky, Mark J; Willey, Vincent J; Skibsted, Simon","year":2025,"journal":"BMJ open diabetes research & care, 13(5)","doi":"10.1136/bmjdrc-2025-005161","pmid":"41093600","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10255","title":"Prevalence of Hypercortisolism in Difficult-to-Control Type 2 Diabetes.","authors":"Buse, John B; Kahn, Steven E; Aroda, Vanita R; Auchus, Richard J; Bailey, Timothy; Bancos, Irina; Busch, Robert S; Christofides, Elena A; DeFronzo, Ralph A; Eilerman, Bradley; Findling, James W; Fonseca, Vivian; Hamidi, Oksana; Handelsman, Yehuda; Miller, Harold J; Ownby, Jonathan G; Parker, John C; Philis-Tsimikas, Athena; Pratley, Richard; Rosenstock, Julio; Shanik, Michael H; Sloan, Lance L; Umpierrez, Guillermo; Tudor, Iulia Cristina; Schlafly, Tina K; Einhorn, Daniel","year":2025,"journal":"Diabetes care, 48(12), 2012-2020","doi":"10.2337/dc24-2841","pmid":"40249765","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10256","title":"Current and Future Implications of Weight Loss Drugs on Liver Disease.","authors":"Bussetty, Arvind; Shah, Nishali; Chandler, Toni Marie; Ghattu, Meghana; Kesavarapu, Keerthana","year":2025,"journal":"Clinics in liver disease, 29(4), 743-753","doi":"10.1016/j.cld.2025.06.005","pmid":"41109700","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10257","title":"Sirtuin 4 accelerates heart failure development by enhancing reactive oxygen species-mediated profibrotic transcriptional signaling.","authors":"Byrne, Nikole J; Koentges, Christoph; Khan, Elisabeth; Pfeil, Katharina; Sandulescu, Robert; Bakshi, Sayan; Költgen, Carolin; Vosko, Ivan; Gollmer, Johannes; Rathner, Thomas; Roth, Günter; Hoffmann, Michael M; Odening, Katja E; Horstmann, Hauke; Potter, Luke A; Bode, Christoph; Wolf, Dennis; Sourij, Harald; Ljubojevic-Holzer, Senka; Wallner, Markus; Rainer, Peter P; Sedej, Simon; Scherr, Daniel; von Lewinski, Dirk; Wende, Adam R; Zirlik, Andreas; Bugger, Heiko","year":2025,"journal":"Journal of molecular and cellular cardiology plus, 12, 100299","doi":"10.1016/j.jmccpl.2025.100299","pmid":"40585275","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10258","title":"Preclinical Proof of Concept for the Single-Protein Anticancer Molecule Targeting Both a Tumor Surface Antigen and an Intracellular Oncoprotein.","authors":"Byun, Kyu Tae; Kim, Boram; Lee, Inbeom; Cho, Junmin; Hwang, Yiseul; Cheon, So Yeong; Kang, Ho Chul; Kim, Chul Geun; Byun, Jung Woo; Paeng, Jin Chul; Park, Dongsun; Park, Jang Woo; Kim, Heejung; Chung, Hye Kyung; Won, Hyung-Sik; Kim, Chan Gil","year":2025,"journal":"Advanced healthcare materials, e02786","doi":"10.1002/adhm.202502786","pmid":"41387314","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10259","title":"Advantage of Semaglutide: Comprehensive Analysis of Metabolic Impact of Semaglutide-Treated and Pair-Fed Rats.","authors":"Byun, Suyeun; Sotzen, Morgan R; Knappenberger, Mya A; Bento, Madison T; Asker, Mohammed; Olekanma, Doris I; Skibicka, Karolina P","year":2025,"journal":"Comprehensive Physiology, 15(6), e70083","doi":"10.1002/cph4.70083","pmid":"41405347","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10260","title":"Liraglutide preserves endothelial function in ophthalmic arteries of septic mice via prevention of oxidative stress.","authors":"Böhm, Elsa Wilma; Omran, Wael; Zadeh, Jenia Kouchek; Arad, Tschingis; Pfeiffer, Norbert; Patzak, Andreas; Oelze, Matthias; Daiber, Andreas; Helmstädter, Johanna; Steven, Sebastian; Gericke, Adrian","year":2025,"journal":"Experimental eye research, 259, 110562","doi":"10.1016/j.exer.2025.110562","pmid":"40744307","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Liraglutide preserved endothelium-dependent vasodilation (acetylcholine responses) in ophthalmic arteries of septic mice while untreated septic mice showed significantly impaired responses. The protective effect was linked to reduced oxidative stress markers: both dihydroethidium staining and NOX2 antibody staining showed elevated oxidative stress in untreated septic arteries but not in liraglutide-treated ones. Importantly, endothelium-independent vasodilation (sodium nitroprusside) and vasoconstriction (phenylephrine) were unaffected across all groups, confirming the dysfunction was specifically endothelial.","whyItMatters":"Sepsis can damage blood vessels throughout the body, including in the eyes, potentially contributing to vision-threatening conditions. This study reveals that GLP-1 receptor activation specifically protects endothelial function in ophthalmic arteries — suggesting that widely prescribed GLP-1 drugs could have unexpected protective benefits for eye health during critical illness.","specificNumbers":"3 groups of mice; 24h post-CLP assessment; significant impairment in ACh response in septic mice; preserved ACh response with liraglutide; increased DHE and NOX2 staining in septic arteries reversed by liraglutide","methodology":"Animal study with three groups: sham surgery controls, septic mice (cecal ligation and puncture), and septic mice treated with liraglutide. After 24 hours, ophthalmic arteries were isolated for videomicroscopy vascular function testing and oxidative stress quantification via PCR, dihydroethidium staining, and NOX2 immunohistochemistry.","limitations":"Mouse model only — no human data. The 24-hour time point captures only acute effects; chronic sepsis outcomes unknown. The cecal ligation model is severe and may not represent all types of sepsis. Specific liraglutide doses and sample sizes per group are not reported in the abstract."},{"rthcId":"RPEP-10261","title":"An overview of benefits and risks of chronic melanocortin-1 receptor activation.","authors":"Böhm, M; Robert, C; Malhotra, S; Clément, K; Farooqi, S","year":2025,"journal":"Journal of the European Academy of Dermatology and Venereology : JEADV, 39(1), 39-51","doi":"10.1111/jdv.20269","pmid":"39082868","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10262","title":"GLP-1 and Its Analogs: Does Sex Matter?","authors":"Börchers, Stina; Skibicka, Karolina P","year":2025,"journal":"Endocrinology, 166(2)","doi":"10.1210/endocr/bqae165","pmid":"39715341","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review found no evidence for major qualitative sex differences in the therapeutic effects of clinically approved GLP-1 analogs — both men and women benefit from these drugs for obesity, diabetes, and cardiovascular disease. However, a growing body of literature identifies quantitative sex differences in the response to GLP-1 and its analogs, meaning the magnitude or specific mechanisms of action may differ between sexes.\n\nNotably, there appears to be an interaction between GLP-1 therapeutics and estrogens, which could affect drug responses in women across different life stages. The review also addresses emerging data on GLP-1 analogs' effects on mood and reproductive function, where sex differences are particularly relevant.","whyItMatters":"GLP-1 analogs are among the most prescribed medications globally, and their use is growing fastest among women — particularly for weight loss. Yet the fundamental science behind how these drugs work has been predominantly studied in male animal models and male-dominated clinical trials. Understanding sex-specific responses is essential for optimizing treatment, predicting side effects, and ensuring equitable care. The estrogen interaction is particularly important for women at different reproductive stages.","specificNumbers":"","methodology":"This is a narrative review article that examines published preclinical (animal) and clinical (human) studies on sex differences in GLP-1 biology and GLP-1 analog therapeutics. The review covers the endogenous GLP-1 system, brain and behavioral effects on appetite and metabolism, clinical outcomes in obesity/diabetes/cardiovascular disease, and effects on mood and reproductive function.","limitations":"As a review, this paper synthesizes existing literature rather than presenting new data. The review itself is limited by the very gap it identifies — insufficient research in female models means there is limited data to review. The authors acknowledge that the absence of evidence for sex differences is not evidence of absence, as many studies simply never tested for them. The narrative review format also means study selection may not be systematic."},{"rthcId":"RPEP-10263","title":"GLP-1 receptor agonist utilization is associated with a low risk of Anesthesia-related complications prior to total joint arthroplasty.","authors":"C Palmer, Ryan; Telang, Sagar S; Kistler, Natalie M; Mayfield, Cory K; Hong, Kurt; Gucev, Gligor; Lieberman, Jay R; Heckmann, Nathanael D","year":2025,"journal":"European journal of orthopaedic surgery & traumatology : orthopedie traumatologie, 36(1), 37","doi":"10.1007/s00590-025-04604-x","pmid":"41351714","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10264","title":"Once-Weekly Semaglutide Improves Body Composition in Spanish Obese Adults with Type 2 Diabetes: A 48-Week Prospective Real-Life Study.","authors":"Caballero-Mateos, Irene; Morales-Portillo, Cristóbal; González Aguilera, Beatriz","year":2025,"journal":"Journal of clinical medicine, 14(15)","doi":"10.3390/jcm14155434","pmid":"40807054","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10265","title":"Evaluation of the Antitumor and Antiproliferative Potential of Synthetic Peptides Derived from IsCT1, Associated with Cisplatin, in Squamous Cell Carcinoma of the Oral Cavity.","authors":"Cabral, Laertty Garcia de Sousa; de Oliveira, Cyntia Silva; Oliveira, Vani Xavier; de Abreu Paulo, Ellen Paim; Poyet, Jean-Luc; Maria, Durvanei Augusto","year":2025,"journal":"Molecules (Basel, Switzerland), 30(12)","doi":"10.3390/molecules30122594","pmid":"40572557","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10266","title":"Antimicrobial peptides-based strategies at the frontline in battling the escalating menace of methicillin-resistant Staphylococcus aureus biofilms.","authors":"Cabuhat, Kevin Smith P; Tan, Troy Vincent C; Ong, Christian Joseph N; Mortel, Ferdinand A; Bacalzo, Grace D; Nuevo, Jose Jurel M; Fortaleza, Jamil Allen G","year":2025,"journal":"European journal of microbiology & immunology","doi":"10.1556/1886.2025.00075","pmid":"41474459","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10267","title":"Antimicrobial Proteinoid Nanostructures via Thermal Condensation of L-Glutamic Acid and L-Tyrosine.","authors":"Cadeddu, Marta; Adams, James R G; La Ragione, Roberto; Whelligan, Daniel K; Stolojan, Vlad; Bernardi, Nadia; Smyrnias, Ioannis; Poddesu, Barbara; Cugia, Giulia; De Forni, Davide; Malfatti, Luca; Carboni, Davide; Pinna, Alessandra; Innocenzi, Plinio","year":2025,"journal":"Nanomaterials (Basel, Switzerland), 15(24)","doi":"10.3390/nano15241846","pmid":"41441460","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10268","title":"A GLP-1R/Y1 receptor/Y2 receptor triple agonist decreases fentanyl-evoked dopamine release in the nucleus accumbens and attenuates fentanyl taking and seeking in rats.","authors":"Caffrey, Antonia; Lavecchia, Enzo; Chichura, Kylie S; Hayes, Matthew R; Doyle, Robert P; Schmidt, Heath D","year":2025,"journal":"British journal of pharmacology, 182(18), 4363-4379","doi":"10.1111/bph.70096","pmid":"40456683","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GEP12, administered at doses of 1.57 or 12.53 μg/kg intraperitoneally, reduced voluntary fentanyl self-administration (2.5 μg/kg IV) in both male and female rats and shifted the fentanyl dose-response curve downward. The drug also reduced fentanyl-seeking behavior during reinstatement after extinction — a model of relapse.\n\nUsing fiber photometry, the researchers demonstrated that GEP12 reduced fentanyl-evoked dopamine release in the nucleus accumbens, identifying a central mechanism for its anti-addiction effects. Importantly, the behaviorally effective doses did not alter food intake or produce malaise-like side effects, suggesting a therapeutic window exists.","whyItMatters":"The opioid crisis has limited effective pharmacotherapies. Current medications like methadone and buprenorphine target opioid receptors directly, but this study explores a completely different approach — using peptide-based drugs that act on appetite and reward circuits. The fact that a GLP-1-based triple agonist can reduce opioid-seeking without causing nausea or food suppression opens a potential new treatment avenue for opioid use disorder.","specificNumbers":"","methodology":"Rats were allowed to self-administer intravenous fentanyl (2.5 μg/kg per infusion) for 21 days to establish addiction-like behavior. They were then pretreated with either vehicle or GEP12 (1.57 or 12.53 μg/kg, injected into the abdomen) before test sessions measuring drug-taking and drug-seeking. In vivo fiber photometry was used to measure real-time dopamine release in the nucleus accumbens during fentanyl self-administration.","limitations":"This is an animal study using rats, and the results may not translate directly to humans. The study did not test long-term safety or efficacy, and the specific doses used in rats would need to be recalculated for human trials. The reinstatement model is an approximation of human relapse, not a perfect analog."},{"rthcId":"RPEP-10269","title":"Semaglutide and Nonarteritic Anterior Ischemic Optic Neuropathy.","authors":"Cai, Cindy X; Hribar, Michelle; Baxter, Sally; Goetz, Kerry; Swaminathan, Swarup S; Flowers, Alexis; Brown, Eric N; Toy, Brian; Xu, Benjamin; Chen, John; Chen, Aiyin; Wang, Sophia; Lee, Cecilia; Leng, Theodore; Ehrlich, Joshua R; Barkmeier, Andrew; Armbrust, Karen R; Boland, Michael V; Dorr, David; Boyce, Danielle; Alshammari, Thamir; Swerdel, Joel; Suchard, Marc A; Schuemie, Martijn; Bu, Fan; Sena, Anthony G; Hripcsak, George; Nishimura, Akihiko; Nagy, Paul; Falconer, Thomas; DuVall, Scott L; Matheny, Michael; Viernes, Benjamin; O'Brien, William; Zhang, Linying; Martin, Benjamin; Westlund, Erik; Mathioudakis, Nestoras; Fan, Ruochong; Wilcox, Adam; Lai, Albert; Stocking, Jacqueline C; Takkouche, Sahar; Lee, Lok Hin; Xie, Yangyiran; Humes, Izabelle; McCoy, David B; Adibuzzaman, Mohammad; Areaux, Raymond G; Rojas-Carabali, William; Brash, James; Lee, David A; Weiskopf, Nicole G; Mawn, Louise; Agrawal, Rupesh; Morgan-Cooper, Hannah; Desai, Priya; Ryan, Patrick B","year":2025,"journal":"JAMA ophthalmology, 143(4), 304-314","doi":"10.1001/jamaophthalmol.2024.6555","pmid":"39976940","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10270","title":"Semaglutide and diabetic retinopathy: an OHDSI network study.","authors":"Cai, Cindy Xinji; Nishimura, Akihiko; Baxter, Sally; Goetz, Kerry; Hribar, Michelle; Toy, Brian; Barkmeier, Andrew; Wang, Sophia; Swaminathan, Swarup; Flowers, Alexis; Brown, Eric; Xu, Benjamin; Chen, John; Chen, Aiyin; Leng, Theodore; Boland, Michael; Alshammari, Thamir; Bu, Fan; Falconer, Thomas; Martin, Benjamin; Westlund, Erik; Mathioudakis, Nestoras; Zhang, Linying; Fan, Ruochong; Wilcox, Adam; Lai, Albert; Stocking, Jacqueline C; Xie, Yangyiran; Lee, Lok Hin; Dorr, David; Humes, Izabelle; McCoy, David; Adibuzzaman, Mohammad; Areaux, Raymond; Brash, James; Weiskopf, Nicole; Morgan-Cooper, Hannah; Desai, Priya; Tran, Diep; Rustam, Zainab; Zhu, Gina; Swerdel, Joel; Sena, Anthony; Nagy, Paul; Suchard, Marc; Schuemie, Martijn; Hripcsak, George; Ryan, Patrick","year":2025,"journal":"BMJ open diabetes research & care, 13(6)","doi":"10.1136/bmjdrc-2025-005424","pmid":"41192935","tags":[],"studyType":"retrospective-cohort","evidenceStrength":"high","keyFinding":"In the largest real-world study of its kind — analyzing over 810,000 new semaglutide users across 14 databases — semaglutide showed no increased risk of proliferative diabetic retinopathy (PDR) or treatment-requiring diabetic eye disease compared to other GLP-1 drugs or non-GLP-1 diabetes medications.\n\nSemaglutide's risk of PDR was similar to dulaglutide (HR 0.81), empagliflozin (HR 0.83), and sitagliptin (HR 0.83), and significantly lower than glipizide (HR 0.59, p=0.01). For treatment-requiring retinopathy/macular edema, semaglutide actually showed lower risk than dulaglutide (HR 0.53, p=0.02), sitagliptin (HR 0.46, p=0.008), and glipizide (HR 0.55, p=0.02).\n\nThese findings provide strong reassurance that the retinopathy signal seen in the earlier SUSTAIN 6 trial does not translate into increased real-world eye disease risk.","whyItMatters":"The SUSTAIN 6 trial flagged a potential link between semaglutide and diabetic eye complications, creating concern among clinicians and patients. This massive real-world study — covering 810,000+ patients across 14 databases — provides the most definitive evidence to date that semaglutide does not increase retinopathy risk. In fact, it may lower the risk compared to several other diabetes drugs.","specificNumbers":"n=810,390 semaglutide users · 14 databases · PDR vs dulaglutide: HR 0.81, p=0.51 · PDR vs glipizide: HR 0.59, p=0.01 · DR/DME vs sitagliptin: HR 0.46, p=0.008 · 2017–2023","methodology":"Retrospective cohort study using 14 databases (6 administrative claims, 8 electronic health records) in the OHDSI Evidence Network. New semaglutide users for type 2 diabetes were compared to users of other GLP-1 drugs (dulaglutide, exenatide) and non-GLP-1 drugs (empagliflozin, sitagliptin, glipizide) using propensity score-adjusted Cox proportional hazards models. Network-wide estimates were generated via random-effects meta-analysis.","limitations":"This is a retrospective observational study, not a randomized trial, so residual confounding is possible despite propensity score adjustment. Claims and EHR data may have coding inaccuracies for eye disease diagnoses. The study period (2017–2023) may not capture very long-term effects. Patients with pre-existing severe retinopathy may have been less likely to be prescribed semaglutide, potentially biasing results."},{"rthcId":"RPEP-10271","title":"Antimicrobial peptide hydrogels: synthesis, ROS regulation mechanism, and multimodal therapeutic applications in drug delivery systems.","authors":"Cai, Dingjun; Li, Canhong; Zhu, Taifu; Li, Ruiqi; Zhang, Mu; Li, Xiaoling; Liu, Yilong; Dai, Zhifei; Wan, Lei; Lu, Haibin","year":2025,"journal":"Journal of materials chemistry. B, 13(45), 14556-14592","doi":"10.1039/d5tb01846c","pmid":"41122848","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review consolidates current knowledge on antimicrobial peptide hydrogels, highlighting that hydrogel encapsulation addresses the two main clinical barriers for AMPs: pH-dependent instability and enzymatic degradation in vivo.\n\nA particular focus is placed on reactive oxygen species (ROS) modulation as a key therapeutic mechanism. The authors catalog applications across at least seven biomedical domains — antifungal therapy, wound healing, cancer treatment, bioimaging, nucleic acid delivery, immunomodulation, and surgical implants — demonstrating the versatility of the AMP-hydrogel platform.","whyItMatters":"Antibiotic resistance is one of the most urgent global health threats. Antimicrobial peptides are a promising alternative, but their fragility has stalled clinical adoption. By mapping out how hydrogel delivery systems solve these stability problems, this review provides a roadmap for translating AMP research into real-world medical products.","specificNumbers":"","methodology":"This is a comprehensive literature review. The authors synthesized findings from published studies on AMP hydrogel design, synthesis strategies, ROS-related mechanisms of action, and multimodal therapeutic applications. No original experimental data were generated.","limitations":"As a review, it does not generate new experimental data. The field it covers is still largely preclinical, so most of the applications discussed have not yet been validated in human clinical trials. The review may also be subject to publication bias toward positive results in the underlying studies."},{"rthcId":"RPEP-10272","title":"Liraglutide combined with HIIT preserves contractile apparatus and blunts the progression of heart failure in diabetic cardiomyopathy rats.","authors":"Cai, Huan; Dai, Chengye; Liu, Jingqin; Chen, Shuchun","year":2025,"journal":"Scientific reports, 15(1), 5051","doi":"10.1038/s41598-025-85699-4","pmid":"39934246","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10273","title":"Circulating miRNA-486 as a novel diagnostic biomarker for right ventricular remodeling.","authors":"Cai, Huiling; Yu, Cheng; Li, Xiuchuan; Wang, Xuenan; Yang, Yongjian; Lan, Cong","year":2025,"journal":"Frontiers in cardiovascular medicine, 12, 1518022","doi":"10.3389/fcvm.2025.1518022","pmid":"39944601","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10274","title":"Nociceptive Neurons Promote Myeloid-Derived Suppressor Cell Mobilization to Alleviate Post-Stroke Neuroinflammation.","authors":"Cai, Lingxin; Zhou, Jiayin; Cao, Xinran; Huang, Huaping; Xie, Qin; Chu, Haifeng; Chen, Gao; Jin, Lulu; Mao, Zhengwei; Yan, Feng","year":2025,"journal":"Theranostics, 15(17), 8897-8915","doi":"10.7150/thno.119474","pmid":"40963921","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10275","title":"Upper-gastrointestinal tract metabolite profile regulates glycaemic and satiety responses to meals with contrasting structure: a pilot study.","authors":"Cai, Mingzhu; Tejpal, Shilpa; Tashkova, Martina; Ryden, Peter; Perez-Moral, Natalia; Saha, Shikha; Garcia-Perez, Isabel; Serrano Contreras, Jose Ivan; Wist, Julien; Holmes, Elaine; Bernal, Andres; Dou, Bowen; Becker, Georgia Franco; Frost, Gary; Edwards, Cathrina","year":2025,"journal":"Nature metabolism, 7(7), 1459-1475","doi":"10.1038/s42255-025-01309-7","pmid":"40542296","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10276","title":"Compact All-Fiber SERS Probe Sensor Based on the MMF-NCF Structure with Self-Assembled Gold Nanoparticles.","authors":"Cai, Peng; Xu, Tiantian; Wei, Hangan; He, Huili; Li, Fu","year":2025,"journal":"Sensors (Basel, Switzerland), 25(17)","doi":"10.3390/s25175221","pmid":"40942649","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10277","title":"Exploring the Antimicrobial and Immunomodulatory Potential of Gecko-Derived Cathelicidin Gj-CATH5.","authors":"Cai, Shasha; Gao, Ningyang; Wang, Junhan; Li, Jing","year":2025,"journal":"Biomolecules, 15(7)","doi":"10.3390/biom15070908","pmid":"40723780","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10278","title":"Targeting sphingosine-1-phosphate receptor 1 alleviates neuropathic pain associated with pancreatic ductal adenocarcinoma in mice and inhibits tumor progression.","authors":"Cai, Shen-Quan; Zhang, Yi-Xuan; Wang, Chun; Gao, Yu; Wang, Ting-Yu; Xu, Fang-Ning; Liu, Qing-Zheng; Yin, Jing; Zhang, Zhi-Jie; Zhang, Shu; Duan, Muan-Lin; Huang, Ying; Tao, Gao-Jian","year":2025,"journal":"Molecular pain, 21, 17448069251371549","doi":"10.1177/17448069251371549","pmid":"40804635","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In PDAC patients, S1PR1 levels in intrapancreatic nerves were significantly higher in those experiencing cancer-associated pain versus those without pain. In a mouse orthotopic pancreatic cancer model:\n\n• S1PR1 was upregulated in dorsal root ganglia (DRGs) and colocalized with neurons and satellite glial cells\n• Intrathecal injection of S1PR1 antagonists W146 and FTY720 effectively alleviated pain hypersensitivity\n• Both antagonists suppressed the upregulation of TRPV1 (a pain-sensing ion channel) and CGRP (calcitonin gene-related peptide, a key pain-signaling neuropeptide)\n• FTY720 additionally demonstrated partial anti-tumor effects on pancreatic cancer progression\n\nThe finding that S1PR1 blockade suppresses CGRP connects this sphingolipid pathway to the same neuropeptide signaling axis targeted by migraine therapies (anti-CGRP antibodies).","whyItMatters":"Pancreatic cancer pain is among the most severe of any cancer type and poorly controlled by existing therapies. Finding that S1PR1 drives this pain through CGRP and TRPV1 upregulation provides both a new therapeutic target and a mechanistic link to established pain pathways. FTY720 (fingolimod) is already FDA-approved for multiple sclerosis, potentially accelerating its repurposing for cancer pain management.","specificNumbers":"","methodology":"Combined human and mouse study. Human component: histopathological sections and pain data from surgically resected PDAC patients, with S1PR1 immunohistochemistry in intrapancreatic nerves. Mouse component: orthotopic transplantation of MT5 pancreatic cancer cells in C57BL/6J mice, with pain assessment via abdominal mechanical hyperalgesia, hunch scoring, and open-field tests. S1PR1 expression and localization were characterized in DRGs. S1PR1 antagonists (W146, FTY720) were administered intrathecally to test analgesic and anti-tumor effects.","limitations":"The mouse model used orthotopic tumor transplantation rather than spontaneous cancer development, which may not fully replicate human disease progression. Intrathecal drug delivery is impractical for most patients. The human component was observational (correlation between S1PR1 levels and pain), not interventional. FTY720's immunosuppressive properties could be problematic in cancer patients. The anti-tumor effects were described as 'partial' without quantification in the abstract."},{"rthcId":"RPEP-10279","title":"The Liraglutide-Induced Pemphigus Vulgaris: A First Case Report Highlighting Autoimmune Risks of GLP-1 Receptor Agonists.","authors":"Cai, Shuning; Zhang, Zhenyu; Ding, Wei; Zhou, Shuting; Qiu, Xuemei; Hou, Feifei; Wu, Chuanji; Shen, Zhengzhong; Feng, Xiaodong; Jiang, Lu","year":2025,"journal":"Endocrine, metabolic & immune disorders drug targets","doi":"10.2174/0118715303361089250320050246","pmid":"40264312","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10280","title":"The Cardiovascular Outcomes Between Liraglutide and Dulaglutide Among Different Chronic Kidney Disease Stages in Patients With Type 2 Diabetes.","authors":"Cai, Yu-Xuan; Liu, Feng-Hsuan; Sun, Jui-Hung; Lin, Chia-Hung","year":2025,"journal":"Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists, 31(3), 292-297","doi":"10.1016/j.eprac.2024.11.016","pmid":"39689782","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 1,572 T2DM patients (945 liraglutide, 627 dulaglutide), there was no overall significant difference in MACE between the two drugs. However, liraglutide users showed a significant increase in MACE with worsening kidney function:\n\n- eGFR 60–89: HR 1.401 (95% CI 0.663–2.958)\n- eGFR <60: HR 4.078 (95% CI 1.111–14.971, P = 0.0079)\n\nThis trend was not observed with dulaglutide (P = 0.1906), suggesting dulaglutide may maintain cardiovascular protection across CKD stages while liraglutide's benefit diminishes with declining renal function.","whyItMatters":"Many diabetes patients also have chronic kidney disease, and choosing the right GLP-1 receptor agonist for these patients is clinically important. This study suggests the choice between liraglutide and dulaglutide may matter more than previously thought, particularly for patients with advancing kidney disease.","specificNumbers":"","methodology":"Retrospective analysis of 362,842 T2DM patients from the Chang Gung Research Database (Taiwan, 2011–2019). After exclusion criteria, 1,572 GLP-1 RA users were included. MACE incidence was compared between liraglutide and dulaglutide across CKD stages. Secondary outcomes included kidney function deterioration, renal disease, UTIs, pancreatitis, amputations, and cancers.","limitations":"This is a retrospective observational study from a single healthcare system in Taiwan, limiting generalizability. The sample sizes in advanced CKD subgroups were small, leading to wide confidence intervals. The study could not control for all confounders, and the reason for the differential CKD interaction is unclear. It does not include newer agents like semaglutide or tirzepatide."},{"rthcId":"RPEP-10281","title":"Enhancing transdermal delivery of chrysomycin A for the treatment of cutaneous melanoma and MRSA infections using Skin-Penetrating Peptide-Functionalized deformable liposomes.","authors":"Cai, Yue; Zhang, Xinrui; Hu, Wentao; Song, Fuhang; Wang, Hong; Zhang, Huawei; Sun, Xuanrong","year":2025,"journal":"International journal of pharmaceutics, 670, 125130","doi":"10.1016/j.ijpharm.2024.125130","pmid":"39722374","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10282","title":"Bioactive Peptides from Quinoa (Chenopodium quinoa Willd.) as Modulators of the Gut Microbiome: A Scoping Review of Preclinical Evidence.","authors":"Caicedo, Nicolás; Liscano, Yamil; Oñate-Garzón, Jose","year":2025,"journal":"Nutrients, 17(20)","doi":"10.3390/nu17203215","pmid":"41156468","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10283","title":"Incretin impact on gastric function in obesity: physiology, and pharmacological, surgical and endoscopic treatments.","authors":"Camilleri, Michael","year":2025,"journal":"The Journal of physiology, 603(24), 7713-7729","doi":"10.1113/JP287535","pmid":"39580615","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10284","title":"Profile of opioid peptide receptors in GnRH and kisspeptin neurons of female mice and rats.","authors":"Campideli-Santana, Ana C; Coolen, Lique M; Lehman, Michael N; Szawka, Raphael E","year":2025,"journal":"Journal of neuroendocrinology, 37(10), e70075","doi":"10.1111/jne.70075","pmid":"40765036","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Using RNAscope technology, researchers mapped opioid receptor expression in reproductive hormone neurons of female mice and rats. In mice, kappa-opioid receptors (Oprk1) were the predominant type in arcuate nucleus kisspeptin neurons, and their expression decreased during proestrus (high estrogen) compared to metestrus (low estrogen). All three opioid receptor types (kappa, mu, delta) were expressed in GnRH neurons and rostral periventricular kisspeptin neurons. In rats, arcuate kisspeptin neurons showed the same kappa receptor cycling pattern but with equal expression of all three receptor types rather than kappa predominance. The findings implicate kappa-opioid receptors in the estrogen feedback control of LH secretion.","whyItMatters":"Understanding how opioid peptides regulate reproductive hormone secretion is crucial for fertility medicine and conditions like polycystic ovary syndrome and hypothalamic amenorrhea. This study provides the most detailed map to date of which opioid receptors are expressed in the specific neuron populations that control ovulation, revealing species differences between mice and rats that are important for interpreting preclinical reproductive research.","specificNumbers":"","methodology":"RNAscope in situ hybridization was used to detect kappa (Oprk1), mu (Oprm1), and delta (Oprd1) opioid receptor mRNA in GnRH neurons and kisspeptin neurons of the rostral periventricular area of the third ventricle (RP3V) and arcuate nucleus in cycling female mice and rats. Colocalization was quantified during metestrus (low ovarian steroids) and proestrus (high ovarian steroids) to assess hormonal regulation of receptor expression.","limitations":"This study was conducted in mice and rats only — human reproductive neuron opioid receptor expression may differ. RNAscope detects mRNA rather than functional protein, so receptor expression patterns may not directly reflect functional signaling. The study examined only two time points in the estrous cycle (metestrus and proestrus). The functional consequences of the observed receptor changes on LH secretion are inferred but not directly tested."},{"rthcId":"RPEP-10285","title":"Knowledge, attitudes, and practices in obesity among trained and in-training primary care providers in an urban safety-net hospital system.","authors":"Campos, Alejandro; Fantasia, Kathryn L; Rizo, Ivania","year":2025,"journal":"Obesity pillars, 15, 100185","doi":"10.1016/j.obpill.2025.100185","pmid":"40546447","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10286","title":"Quality of information and social norms in Spanish-speaking TikTok videos as levers of commercial practices: The case of semaglutide.","authors":"Campos-Rivera, Paola Abril; Alfaro-Ponce, Berenice; Ramírez-Pérez, Michelle; Bernal-Serrano, Daniel; Contreras-Loya, David; Wirtz, Veronika J","year":2025,"journal":"Social science & medicine (1982), 366, 117646","doi":"10.1016/j.socscimed.2024.117646","pmid":"39827687","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10287","title":"Review of Fish Neuropeptides: A Novel Perspective on Animal Welfare.","authors":"Campos-Sánchez, Jose Carlos; Cabrera-Álvarez, María José; Saraiva, Joao L","year":2025,"journal":"The Journal of comparative neurology, 533(2), e70029","doi":"10.1002/cne.70029","pmid":"40008573","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10288","title":"Impact of Right Atrial Appendage Ligation vs. Repair on Serum Atrial Natriuretic Peptide, Brain Natriuretic Peptide, and Atrial Fibrillation following Coronary Artery Bypass Grafting.","authors":"Can, Murat Fatih; Sicim, Hüseyin; Selçuk, İsmail; Selçuk, Ümmühan Nehir; Temizkan, Veysel","year":2025,"journal":"Brazilian journal of cardiovascular surgery, 40(5)","doi":"10.21470/1678-9741-2021-0574","pmid":"40854151","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10289","title":"Dumping Syndrome After Bariatric Surgery: Advanced Nutritional Perspectives and Integrated Pharmacological Management.","authors":"Cano, Raquel; Rodríguez, Daniel; Duran, Pablo; Cano, Clímaco; Rojas-Gómez, Diana; Rivera-Porras, Diego; Barboza-González, Paola; Fuentes-Barría, Héctor; Angarita, Lissé; Boscan, Arturo; Bermúdez, Valmore","year":2025,"journal":"Nutrients, 17(19)","doi":"10.3390/nu17193123","pmid":"41097200","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10290","title":"Development of a 3D-printable bioactive polycaprolactone-collagen peptides filament for biomedical applications.","authors":"Cantella, Stefano; Badini, Silvia; Bollati, Carlotta; Madar Saheb, Mushtaq Alam; Viganò, Roberto; Lammi, Carmen; Pugliese, Raffaele; Graziosi, Serena","year":2025,"journal":"Scientific reports, 15(1), 44513","doi":"10.1038/s41598-025-28030-5","pmid":"41444724","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A PCL-collagen peptide composite filament was successfully fabricated using a scalable, non-toxic solvent-assisted blending process on a desktop extrusion system. The collagen peptides enhanced tensile stiffness through intermolecular hydrogen bonding with PCL while maintaining the matrix's crystalline and thermal properties.\n\nThe composite was confirmed biocompatible and exhibited intrinsic bioactive capabilities from the collagen peptides. Degradation studies showed the PCL degradation rate could be tuned. Complex 3D scaffolds based on Triply Periodic Minimal Surfaces (TPMS) were successfully fabricated using standard fused filament fabrication printing, demonstrating practical applicability.","whyItMatters":"Custom 3D-printed medical implants and scaffolds could revolutionize regenerative medicine by creating patient-specific devices. However, most 3D-printable plastics lack biological activity. By integrating collagen peptides — which cells naturally recognize and interact with — into a printable format, this study creates a material that is both manufacturable and biologically functional, bringing personalized bioactive implants closer to reality.","specificNumbers":"","methodology":"Virgin and recycled PCL were blended with collagen peptides using a solvent-assisted process and extruded into 3D-printable filaments on a custom desktop system. The composites were characterized using scanning electron microscopy (SEM), X-ray diffraction (XRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and intrinsic fluorescence spectroscopy. Mechanical properties were tested via tensile testing. Biocompatibility was evaluated through cell studies, and degradation behavior was assessed over time.","limitations":"The study focuses on material development and characterization — no in vivo testing in animals or humans was performed. The lab-scale process and use of recycled PCL reduced tensile modulus, which may limit some applications. Long-term bioactivity of the collagen peptides after the extrusion process (which involves heat) was not comprehensively assessed. Sterilization compatibility was not addressed. Cell studies demonstrated biocompatibility but not functional tissue regeneration."},{"rthcId":"RPEP-10291","title":"Structural and dynamic features of cagrilintide binding to calcitonin and amylin receptors.","authors":"Cao, Jianjun; Belousoff, Matthew J; Johnson, Rachel M; Keov, Peter; Mariam, Zamara; Deganutti, Giuseppe; Christopoulos, George; Hick, Caroline A; Reedtz-Runge, Steffen; Glendorf, Tine; Ballarín-González, Borja; Raun, Kirsten; Bayly-Jones, Charles; Wootten, Denise; Sexton, Patrick M","year":2025,"journal":"Nature communications, 16(1), 3389","doi":"10.1038/s41467-025-58680-y","pmid":"40204768","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10292","title":"Chronic diarrhea related to neuroblastoma: the important role of vasoactive intestinal peptide in tumor pathology and survival.","authors":"Cao, Meng-Ying; Zhang, Kun; Guo, Jing; Dong, Fang; Xu, Ling-Fen","year":2025,"journal":"BMC cancer, 25(1), 457","doi":"10.1186/s12885-025-13870-1","pmid":"40082825","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10293","title":"Integration of hunger and hormonal state gates infant-directed aggression.","authors":"Cao, Mingran; Ammari, Rachida; Chen, Maxwell X; Wai, Patty; Jamieson, Bradley B; Liang, Swang; Husain, Basma F A; Sahni, Aashna; Legrave, Nathalie; Salgarella, Irene; MacRae, James; Strom, Molly; Kohl, Johannes","year":2025,"journal":"Nature, 648(8092), 138-145","doi":"10.1038/s41586-025-09651-2","pmid":"41125886","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10294","title":"Weight Recidivism After Bariatric Surgery: A Narrative Review.","authors":"Cao, Qilin; Kazi, Hooria; Merchant, Aziz M; Jawed, Aram E","year":2025,"journal":"The American surgeon, 91(9), 1534-1547","doi":"10.1177/00031348251337161","pmid":"40252043","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10295","title":"Beta-Defensin1 from Ctenopharyngodon idella exerts immunomodulatory effects through CiHsp70-mediated antigen processing and presentation pathway activation.","authors":"Cao, Shoulin; Chang, Jiaojiao; Li, Jinnian; Liu, Xuelan","year":2025,"journal":"Fish & shellfish immunology, 162, 110367","doi":"10.1016/j.fsi.2025.110367","pmid":"40286949","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10296","title":"Pathophysiology of type 2 diabetes: A focus on the metabolic differences among southeast Asian, Chinese and Indian populations and how this impacts treatment.","authors":"Cao, Yuzi; Widyahening, Indah; Sun, Xiaodong; Li, Sheyu","year":2025,"journal":"Diabetes, obesity & metabolism, 27 Suppl 10(Suppl 10), 3-14","doi":"10.1111/dom.70060","pmid":"40859465","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10297","title":"Scorpion Venom-Derived Peptides: A New Weapon Against Carbapenem-Resistant Acinetobacter baumannii.","authors":"Capasso, Carla; Zannella, Carla; Giugliano, Rosa; Chianese, Annalisa; Monti, Alessandra; Donadio, Federica; Esposito, Emanuela; Marino, Gerardo; Doti, Nunzianna; De Filippis, Anna; Galdiero, Massimiliano","year":2025,"journal":"Microorganisms, 14(1)","doi":"10.3390/microorganisms14010068","pmid":"41597588","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10298","title":"Cost-Effectiveness of Tirzepatide Versus Liraglutide, Both Adjunct to Diet and Exercise, for Patients with Obesity or Overweight: A UK Perspective.","authors":"Capehorn, Matthew; Johansson, Erin; Davies, Alun; Evans, Jerome; Godbeer, Fiona; van Hest, Naomi; Cotterill, Georgina; Tolley, Keith","year":2025,"journal":"Advances in therapy, 42(10), 5055-5071","doi":"10.1007/s12325-025-03288-3","pmid":"40788459","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10299","title":"Efficacy and Safety of Tirzepatide in Refractory Hypoglycemia Associated with Esophagojejunostomy.","authors":"Caporusso, Mariangela; Di Gioia, Ludovico; Manicone, Mariangela; Matera, Lucrezia; Giorgino, Francesco; Perrini, Sebastio","year":2025,"journal":"JCEM case reports, 3(11), luaf249","doi":"10.1210/jcemcr/luaf249","pmid":"41140513","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10300","title":"National Utilization and Expenditure Trends of GLP-1 Receptor Agonists and Dual GLP-1/GIP Agonist in Croatia, 2017-2024.","authors":"Car, Mate; Erceg, Damir; Udovičić, Mario; Bokun, Tomislav; Rahelić, Dario","year":2025,"journal":"Medicina (Kaunas, Lithuania), 61(12)","doi":"10.3390/medicina61122210","pmid":"41470212","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10301","title":"Supramolecular nanostructure mimics GDNF trophic effects in vitro on human dopaminergic neurons.","authors":"Carballo-Molina, Oscar A; Kolberg-Edelbrock, Alexandra N; Alvarez-Saavedra, Matías; Álvarez, Zaida; Fyrner, Timmy; Perez-Rosello, Tamara; Syrgiannis, Zois; Chin, Stacey M; Takata, Nozomu; Strong, Madison; Palmer, Liam C; James Surmeier, D; Stupp, Samuel I","year":2025,"journal":"NPJ Regenerative medicine, 10(1), 37","doi":"10.1038/s41536-025-00424-z","pmid":"40781074","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10302","title":"Impact of anti-CGRP monoclonal antibodies on treatment satisfaction and quality of life in patients with resistant migraine: a retrospective real-world study.","authors":"Cardona-Roca, Laura; Seguí-Solanes, Carlos; Cano-Alonso, Manuel; Sosa-Pons, Alba; Almendros-Abad, Nuria; Sola, Nuria Rudi","year":2025,"journal":"BMC neurology, 25(1), 418","doi":"10.1186/s12883-025-04384-1","pmid":"41087959","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10303","title":"Pharmacological characterization of vampire bat-derived CGRP at the human CGRP receptor in the Xenopus oocyte system.","authors":"Carleer, Kathleen; Raval, Kavit; Tudzarova, Slavica; Tytgat, Jan","year":2025,"journal":"Toxicon : official journal of the International Society on Toxinology, 265, 108466","doi":"10.1016/j.toxicon.2025.108466","pmid":"40578569","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10304","title":"A retrospective evaluation of glucagon-like peptide-1 receptor agonists in systemic lupus erythematosus patients.","authors":"Carlucci, Philip M; Cohen, Brooke; Saxena, Amit; Belmont, H Michael; Masson, Mala; Gold, Heather T; Buyon, Jill; Izmirly, Peter","year":2025,"journal":"Rheumatology (Oxford, England), 64(5), 3085-3089","doi":"10.1093/rheumatology/keae547","pmid":"39388251","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 18 lupus patients treated with GLP-1 receptor agonists from the NYU Lupus Cohort, only one mild-to-moderate flare occurred at 6–10 months, and no patients accumulated new SLE classification criteria during follow-up. The flare rate was within expected background rates for the disease.\n\nBMI reductions were statistically significant: median BMI decreased by 3% at 1–4 months (P = 0.002) and by 13% at 6–10 months (P = 0.001). Notably, 9 of 18 patients (50%) were initially denied insurance coverage for their GLP-1RA prescription. Only 24 of 1,211 patients (2%) in the entire lupus cohort had received a GLP-1RA, suggesting significant underutilization.","whyItMatters":"Lupus patients face elevated cardiovascular risk and metabolic complications, making GLP-1RAs potentially valuable. However, a published case of drug-induced lupus from GLP-1RA use created uncertainty about safety in this population. This small but important study provides initial reassurance that these drugs don't appear to trigger lupus flares, while delivering meaningful weight loss — potentially addressing both metabolic and cardiovascular risks in SLE patients.","specificNumbers":"","methodology":"This was a retrospective analysis of patients in the NYU Lupus Cohort who had used a GLP-1 receptor agonist. Of 1,211 cohort patients, 24 had received a GLP-1RA; 6 were excluded due to insufficient documentation, leaving 18 for analysis. Patient characteristics, disease activity, and BMI were assessed at baseline (most recent rheumatology visit before starting GLP-1RA), 1–4 months, and 6–10 months after initiation.","limitations":"This is a very small (n=18), single-center, retrospective, descriptive study without a control group. The sample size is insufficient to detect uncommon adverse events or statistically rare lupus flares. The follow-up period (6–10 months) is short relative to the chronic nature of SLE. Selection bias is likely — patients chosen for GLP-1RA therapy may have had more stable disease. The study cannot distinguish whether the low flare rate is because GLP-1RAs are truly safe in lupus or because the sample was too small and follow-up too short to detect problems."},{"rthcId":"RPEP-10305","title":"GLP-1 Receptor Agonists in Mood Disorders: A Psychiatric Perspective.","authors":"Carmellini, Pietro; Cuomo, Alessandro; Rescalli, Maria Beatrice; Fagiolini, Andrea","year":2025,"journal":"Life (Basel, Switzerland), 15(9)","doi":"10.3390/life15091422","pmid":"41010364","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10306","title":"Patient Experience of Treatment with Tirzepatide for Weight Management: Exit Interviews from SURMOUNT-4.","authors":"Carmichael, Chloe; Jouravskaya, Irina; Collins, Elizabeth; Burns, Danielle; Poon, Jiat Ling; Kitchen, Helen; Mojdami, Donna; Murphy, Madhumita; Ahmad, Nadia; Kanu, Chisom","year":2025,"journal":"The patient, 18(3), 225-236","doi":"10.1007/s40271-025-00730-0","pmid":"39987302","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"All 86 participants reported at least one perceived benefit of tirzepatide during the SURMOUNT-4 open-label phase, with the most commonly mentioned being improved appetite control, increased energy, and improved clothing fit.\n\nDespite gastrointestinal side effects being common, participants generally valued the efficacy of tirzepatide enough to tolerate them. The single-use injection pen device was rated as easy to use. Most participants expressed willingness to continue tirzepatide treatment. Participants reported wide-ranging life improvements beyond direct pharmacological effects, suggesting the drug's impact extends beyond weight loss alone.","whyItMatters":"Clinical trials typically report numbers — weight lost, side effects, lab values. This study captures what those numbers mean to real people. Understanding patient experience is crucial because even effective medications fail if people won't take them. The finding that participants valued tirzepatide's benefits enough to tolerate side effects and wanted to continue treatment provides real-world insight that complements the clinical data and helps set expectations for patients starting the medication.","specificNumbers":"","methodology":"Qualitative study using semi-structured online exit interviews with 86 adults from 16 US-based SURMOUNT-4 clinical trial sites. Interviews covered experiences with receiving tirzepatide, using the injection pen device, and overall trial experience. Audio recordings were transcribed and analyzed using content analysis methodology. Participants were recruited after completing their participation in the SURMOUNT-4 randomized withdrawal trial.","limitations":"Selection bias is a significant concern — participants who had more positive experiences were likely more inclined to participate in exit interviews. The study population was 83% female and entirely US-based, limiting generalizability. All participants had been in the open-label phase first, so they knew they were receiving active drug. The qualitative methodology cannot quantify the magnitude of benefits or systematically compare to placebo experiences."},{"rthcId":"RPEP-10307","title":"Combating Gram-negative infections: The role of antimicrobial peptides and nanotechnology in overcoming antibiotic resistance.","authors":"Carnero Canales, Christian S; Marquez Cazorla, Jessica Ingrid; Marquez Cazorla, Renzo Marianito; Sábio, Rafael Miguel; Santos, Hélder A; Pavan, Fernando Rogério","year":2025,"journal":"Materials today. Bio, 35, 102381","doi":"10.1016/j.mtbio.2025.102381","pmid":"41142413","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10308","title":"Clinical and Metabolic Effects of Incretin-Based Pharmacotherapy in Normal-Weight Patients With Type 2 Diabetes: A Real-World Analysis.","authors":"Carson, Erin; Khaleq, Fatima; McDonald, Cassidy; Smith, Nadine; Rodriguez Colon, Alanis","year":2025,"journal":"Cureus, 17(7), e88898","doi":"10.7759/cureus.88898","pmid":"40881557","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10309","title":"Association of semaglutide with less limb events in people with type 2 diabetes and peripheral artery disease or foot ulcers: An observational study comparing matched cohorts.","authors":"Caruso, Paola; Angelino, Silvia; Matrone, Rita; Scappaticcio, Lorenzo; Longo, Miriam; Volatile, Alessandra; Petrizzo, Michela; Pontillo, Alessandro; Caputo, Mariangela; Carbone, Carla; Gicchino, Maurizio; Bellastella, Giuseppe; Giugliano, Dario; Esposito, Katherine; Maiorino, Maria Ida","year":2025,"journal":"Diabetes, obesity & metabolism, 27(10), 5506-5513","doi":"10.1111/dom.16594","pmid":"40620210","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10310","title":"Liraglutide improves peripheral perfusion and markers of angiogenesis and inflammation in people with type 2 diabetes and peripheral artery disease: An 18-month follow-up of a randomized clinical trial.","authors":"Caruso, Paola; Maiorino, Maria Ida; Longo, Miriam; Maio, Antonietta; Scappaticcio, Lorenzo; Di Martino, Nicole; Carbone, Carla; Barrasso, Mariluce; Caputo, Mariangela; Gicchino, Maurizio; Bellastella, Giuseppe; Giugliano, Dario; Esposito, Katherine","year":2025,"journal":"Diabetes, obesity & metabolism, 27(7), 3891-3900","doi":"10.1111/dom.16419","pmid":"40276845","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10311","title":"The potential of antimicrobial peptides to treat oral infections and cancer.","authors":"Carvalho de Paula, Ana Emilia; Silva Siqueira, Carla; Lorenzón, Esteban Nicolás","year":2025,"journal":"Frontiers in medicine, 12, 1712514","doi":"10.3389/fmed.2025.1712514","pmid":"41567672","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10312","title":"Calcitonin gene-related peptide monoclonal antibodies and medication overuse headache: is stopping excessive pain medication still necessary?","authors":"Carvalho, João José Freitas de","year":2025,"journal":"Arquivos de neuro-psiquiatria, 83(9), 1-3","doi":"10.1055/s-0045-1809658","pmid":"40720969","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10313","title":"A National Cross-Sectional Survey on Real-World Experiences of Calcitonin Gene-Related Peptide (CGRP) Monoclonal Antibody Use in Adults with Migraine in Finland.","authors":"Casey, Caroline S; Pölkki, Mari; Suvanen, Elisa K; Iso-Mustajärvi, Ilona; Purmonen, Timo; Peltonen, Essi J; Appel, Camilla K; Patel, Niraj J; Von Arx, Lill-Brith","year":2025,"journal":"Pain and therapy, 14(3), 1045-1061","doi":"10.1007/s40122-025-00719-5","pmid":"40189729","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Before CGRP mAb treatment, 73.6% of patients experienced 12 or more monthly migraine headache days; after treatment, only 9.0% did. Conversely, patients with 0-7 monthly migraine days went from 4.5% to 79.7%.\n\nMonthly sick leave of 4+ days dropped from 37.0% to 4.0%. Full-time work/study capacity improved from 47.7% to 76.1%. Median pain intensity decreased from 8.0/10 to 6.0/10. Among the 383 respondents, 78 (20.4%) were on galcanezumab, the newest reimbursed CGRP mAb in Finland, and this group had more prior CGRP mAb switches suggesting they were harder-to-treat cases. Quality of life scores (MSQoL) did not differ between new users (0-6 months) and persistent users (6+ months), suggesting benefits are sustained.","whyItMatters":"Clinical trials showed CGRP antibodies work for migraine, but real-world data from actual patients — not selected trial populations — is essential for understanding true effectiveness. This survey shows that in everyday clinical practice in Finland, CGRP antibodies deliver transformative results for severely affected migraine patients. The improvements in work capacity and sick leave reduction also highlight the economic argument for these treatments.","specificNumbers":"","methodology":"This was a cross-sectional electronic survey distributed through Finnish community pharmacies and Migraine Finland (a patient advocacy group) in 2023. It included 383 adult users of subcutaneous CGRP monoclonal antibodies for migraine prevention. The survey captured monthly migraine headache days, sick leave, work/study capacity, pain intensity, treatment patterns, and quality of life (MSQoL questionnaire) before and after CGRP mAb treatment.","limitations":"This was a cross-sectional survey relying on patient self-report and recall, which introduces recall bias. There was no control group, so improvements cannot be definitively attributed to CGRP mAb treatment alone. The survey was voluntary, potentially introducing selection bias toward satisfied patients. The before/after comparison was retrospective, not prospective. Specific CGRP mAb dosing details and duration of individual use were not detailed in the abstract."},{"rthcId":"RPEP-10314","title":"TNBS colitis induces architectural changes and alpha-synuclein overexpression in mouse distal colon: A morphological study.","authors":"Casini, Arianna; Vivacqua, Giorgio; Ceci, Ludovica; Leone, Stefano; Vaccaro, Rosa; Tagliafierro, Marco; Bassi, Filippo Maria; Vitale, Sara; Bocci, Emanuele; Pannarale, Luigi; Carotti, Simone; Franchitto, Antonio; Mancini, Patrizia; Sferra, Roberta; Vetuschi, Antonella; Latella, Giovanni; Onori, Paolo; Gaudio, Eugenio; Mancinelli, Romina","year":2025,"journal":"Cell and tissue research, 399(2), 247-265","doi":"10.1007/s00441-024-03932-4","pmid":"39656240","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10315","title":"Liraglutide induces enhanced suppression of food intake in mice lacking the growth hormone secretagogue receptor.","authors":"Cassano, Daniela A; Aguggia, Julieta; Giovanini, Lucía; Heredia, Florencia; De Francesco, Pablo N; Andreoli, María F; Schöth, Helgi B; Habib, Abdella M; Fernandez, Gimena; Perello, Mario","year":2025,"journal":"Molecular and cellular endocrinology, 608, 112627","doi":"10.1016/j.mce.2025.112627","pmid":"40738311","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10316","title":"Impact of SGLT2 Inhibitors on Device-Detected Arrhythmias: a Preliminary Study.","authors":"Catrina, Bianca Iulia; Negrea, Mihai Octavian; Tanasescu, Ciprian; Batar, Florina; Bitea, Cornel Ioan; Manitiu, Ioan","year":2025,"journal":"Maedica, 20(3), 459-470","doi":"10.26574/maedica.2025.20.3.459","pmid":"41403812","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10317","title":"Cardiovascular Health in the Shadow of Diabetes and Metabolic Dysfunction-Associated Steatotic Liver Disease: An Emerging Paradigm.","authors":"Caturano, Alfredo; Nilo, Davide; Lorenzo, Giovanni Di; Rocco, Maria; Tagliaferri, Giuseppina; Piacevole, Alessia; Donnarumma, Mariarosaria; Iadicicco, Ilaria; Moretto, Simona Maria; Acierno, Carlo; Sardu, Celestino; Russo, Vincenzo; Perrone, Marco Alfonso; Vetrano, Erica; Galiero, Raffaele; Marfella, Raffaele; Bonfrate, Leonilde; Rinaldi, Luca; Conte, Caterina; Sasso, Ferdinando Carlo","year":2025,"journal":"Reviews in cardiovascular medicine, 26(11), 43143","doi":"10.31083/RCM43143","pmid":"41356318","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review establishes that type 2 diabetes, MASLD, and cardiovascular disease form a clinical triad connected by shared pathophysiology including insulin resistance, chronic inflammation, oxidative stress, and endothelial dysfunction. Under-recognized factors like gut-derived metabolites and adipose tissue dysfunction contribute to disease progression.\n\nSGLT2 inhibitors, GLP-1 receptor agonists, and tirzepatide are identified as cardioprotective agents with potential to address multiple components of this triad simultaneously. However, the review notes gaps in translating these therapies from clinical trials to routine hepatology and cardiology practice.","whyItMatters":"The overlap of diabetes, fatty liver disease, and heart disease affects a huge and growing patient population. Treating these conditions separately leads to fragmented care and missed opportunities. This review makes the case that GLP-1-based therapies and tirzepatide can serve as 'metabolic multi-tools' — addressing multiple conditions simultaneously rather than requiring separate drugs for each.","specificNumbers":"","methodology":"This is a narrative review synthesizing current evidence on the shared pathophysiology of type 2 diabetes, MASLD, and cardiovascular disease. The authors examine diagnostic frameworks, therapeutic approaches including novel pharmacotherapies, and propose an integrated management model.","limitations":"This is a narrative review without new experimental data. While it comprehensively covers the shared pathophysiology and therapeutic landscape, specific clinical outcome data for the triad population using these therapies is still emerging. Translation gaps between trial evidence and real-world clinical practice are acknowledged but not resolved."},{"rthcId":"RPEP-10318","title":"Rethinking the Diabetes-Cardiovascular Disease Continuum: Toward Integrated Care.","authors":"Caturano, Alfredo; Morciano, Cassandra; Zielińska, Katarzyna; Russo, Vincenzo; Perrone, Marco Alfonso; Berra, Cesare Celeste; Conte, Caterina","year":2025,"journal":"Journal of clinical medicine, 14(18)","doi":"10.3390/jcm14186678","pmid":"41010881","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10319","title":"Relationship Between Metabolic and Histological Responses in People With Metabolic Dysfunction- Associated Steatohepatitis With and Without Type 2 Diabetes: Participant-Level Exploratory Analysis of the SYNERGY-NASH Trial With Tirzepatide.","authors":"Caussy, Cyrielle; Cusi, Kenneth; Rosenstock, Julio; Bugianesi, Elisabetta; Thomas, Melissa K; Tang, Yuanyuan; Mather, Kieren J; Loomba, Rohit; Sanyal, Arun J; Hartman, Mark L","year":2025,"journal":"Diabetes care, 48(12), 2074-2083","doi":"10.2337/dc25-1306","pmid":"41066427","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10320","title":"The role of the endogenous opioid system in modulating orthodontic-induced neurogenic inflammation of the dental pulp: A comprehensive review of the literature.","authors":"Caviedes-Bucheli, Javier; Rios-Osorio, Nestor; Ulate-Rodríguez, Esteban; Muñoz-Alvear, Hernan Dario; Gaviño-Orduña, José F; Ortolani-Seltenerich, P Sebastian; Gomez-Sosa, Jose F; Munoz, Hugo Roberto","year":2025,"journal":"International endodontic journal, 58(8), 1126-1145","doi":"10.1111/iej.14251","pmid":"40366100","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Endogenous opioid systems — including somatostatin, dynorphin, β-endorphin, methionine enkephalin, endocannabinoids, and anti-inflammatory cytokines — modulate neurogenic inflammation in the dental pulp triggered by orthodontic forces. This explains why most patients experience minimal pain during orthodontic treatment despite the release of pro-inflammatory neuropeptides (Substance P, CGRP, Neurokinin A). However, when severe orthodontic forces are applied, these endogenous control mechanisms may be overwhelmed, leading to asymptomatic irreversible pulpitis or pulp necrosis.","whyItMatters":"Orthodontic pain management has largely relied on external painkillers, but understanding the body's own opioid peptide systems reveals natural anti-inflammatory pathways that could be harnessed therapeutically. This knowledge could lead to better pain management strategies during orthodontic treatment and help identify patients at risk of pulp damage from excessive forces.","specificNumbers":"","methodology":"Systematic literature review following PRISMA and AMSTAR guidelines, searching PubMed, ISI Web of Science, and Scopus using keywords for orthodontic movement, opioids, and neurogenic inflammation. After removing duplicates and applying inclusion criteria, 38 articles were selected and classified by the opioid peptides analyzed in relation to orthodontic movement and dental pulp.","limitations":"The review synthesizes primarily preclinical and mechanistic studies — direct clinical evidence linking endogenous opioid activity to orthodontic pain outcomes in patients is limited. The 38 included studies likely vary in methodology and quality. The review does not quantify the protective threshold at which endogenous systems become insufficient against severe orthodontic forces."},{"rthcId":"RPEP-10321","title":"Atherosclerotic features in patients with heart failure.","authors":"Ceasovschih, Alexandr; Banjanin, Nikolina; Bednarek, Anna; Beqiraj, Aldo; Cherska, Maria; Ejubović, Malik; Jakubova, Marta; Markos, Sura; Ristovski, Vladimir; Scicali, Roberto; Banach, Maciej; Sorodoc, Victorita; Gotto, Antonio M","year":2025,"journal":"Archives of medical science : AMS, 21(4), 1107-1129","doi":"10.5114/aoms/208372","pmid":"41078932","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10322","title":"Glucagon-like peptide-1 receptor agonists and muscle mass effects.","authors":"Ceasovschih, Alexandr; Asaftei, Andreea; Lupo, Maria Giovanna; Kotlyarov, Stanislav; Bartušková, Hana; Balta, Anastasia; Sorodoc, Victorita; Sorodoc, Laurentiu; Banach, Maciej","year":2025,"journal":"Pharmacological research, 220, 107927","doi":"10.1016/j.phrs.2025.107927","pmid":"40858197","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10323","title":"Benefit-Risk Assessment of GLP-1 Receptor Agonists: Implications for Dermatologists and Plastic Surgeons.","authors":"Cedirian, Stephano; Donati, Monia; Rapparini, Luca; Pampaloni, Francesca; La Placa, Michelangelo; Sgarzani, Rossella; Negosanti, Luca; Raschi, Emanuel; Starace, Michela","year":2025,"journal":"Dermatology and therapy, 15(11), 3173-3193","doi":"10.1007/s13555-025-01537-5","pmid":"40924351","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10324","title":"Clickable Polymer-Based Coatings for Modulating the Interaction of Metal-Organic Framework Nanocrystals with Living Cells.","authors":"Cedrún-Morales, Manuela; Migliavacca, Martina; Ceballos, Manuel; Perez-Maseda, Marta; Zampini, Giulia; Alameda Felgueiras, María Teresa; Ostolaza-Paraiso, Jon; Juanes, Marisa; Rincón, Irene; Fairen-Jimenez, David; Montenegro, Javier; Horcajada, Patricia; Polo, Ester; Pelaz, Beatriz; Del Pino, Pablo","year":2025,"journal":"ACS applied materials & interfaces, 17(17), 24994-25010","doi":"10.1021/acsami.5c01695","pmid":"40257304","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10325","title":"A synergic GLP-1/Acylethanolamide-based combined therapy for MAFLD: Studies in rat models.","authors":"Ceglia, Marialuisa de; Tovar, Rubén; Rodríguez-Pozo, Miguel; Vargas, Antonio; Gavito, Ana; Suárez, Juan; Baixeras, Elena; Rodríguez de Fonseca, Fernando; Decara, Juan","year":2025,"journal":"Biochemical pharmacology, 242(Pt 3), 117364","doi":"10.1016/j.bcp.2025.117364","pmid":"40998023","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10326","title":"Proteomic characterization of venom from Scorpio fuscus (Scorpiones: Scorpionidae) with perspectives for therapeutic applications.","authors":"Celebioglu, Hasan Ufuk; Kandir, Sinan; Gokcek-Sarac, Cigdem; Yagmur, Ersen Aydin; Svensson, Birte; Karakurt, Serdar","year":2025,"journal":"Toxicon : official journal of the International Society on Toxinology, 265, 108506","doi":"10.1016/j.toxicon.2025.108506","pmid":"40714116","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10327","title":"Glucagon-like peptide-1 receptor agonist use is associated with a lower risk of major adverse liver-related outcomes: a meta-analysis of observational cohort studies.","authors":"Celsa, Ciro; Pennisi, Grazia; Tulone, Adele; Ciancimino, Giacinta; Vaccaro, Marco; Infantino, Giuseppe; Di Maria, Gabriele; Pinato, David J; Cabibbo, Giuseppe; Enea, Marco; Mantovani, Alessandro; Tilg, Herbert; Targher, Giovanni; Cammà, Calogero; Petta, Salvatore","year":2025,"journal":"Gut, 74(5), 815-824","doi":"10.1136/gutjnl-2024-334591","pmid":"40015951","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10328","title":"The GLP-1R agonist semaglutide reshapes pancreatic cancer associated fibroblasts reducing collagen proline hydroxylation and favoring T lymphocyte infiltration.","authors":"Cencioni, Chiara; Malatesta, Silvia; Vigiano Benedetti, Virginia; Licursi, Valerio; Perfetto, Livia; Conte, Federica; Ranieri, Danilo; Bartolazzi, Armando; Kunkl, Martina; Tuosto, Loretta; Larghi, Alberto; Piro, Geny; Agostini, Antonio; Tortora, Giampaolo; Corbo, Vincenzo; Carbone, Carmine; Spallotta, Francesco","year":2025,"journal":"Journal of experimental & clinical cancer research : CR, 44(1), 18","doi":"10.1186/s13046-024-03263-w","pmid":"39828692","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10329","title":"Alternative dosing regimens of GLP-1 receptor agonists may reduce costs and maintain weight loss efficacy.","authors":"Cengiz, Anıl; Wu, Calvin C; Lawley, Sean D","year":2025,"journal":"Diabetes, obesity & metabolism, 27(4), 2251-2258","doi":"10.1111/dom.16229","pmid":"39950222","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10330","title":"Incretin mimetics for weight loss forgive nonadherence.","authors":"Cengiz, Anıl; Wu, Calvin C; Lawley, Sean D","year":2025,"journal":"Diabetes, obesity & metabolism, 27(8), 4109-4117","doi":"10.1111/dom.16438","pmid":"40364508","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10331","title":"Effects of tirzepatide on weight management in patients with and without diabetes: a systematic review and meta-analysis.","authors":"Cerchi, Eduardo; Santo, Paula Arruda do Espírito; de Oliveira, Mariana Carvalho; Janovsky, Carolina Castro Porto Silva; Halpern, Bruno","year":2025,"journal":"International journal of obesity (2005), 49(12), 2415-2425","doi":"10.1038/s41366-025-01920-4","pmid":"41015578","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10332","title":"Antimicrobial peptide LL-37 increases rhinovirus-induced interferon β expression in human airway epithelial cells through a Ca2+-dependent mechanism.","authors":"Cerps, Samuel; Ramu, Sangeetha; Gidlöf, Olof; Menzel, Mandy; Swärd, Karl; Uller, Lena; Nilsson, Bengt-Olof","year":2025,"journal":"Biochemistry and biophysics reports, 43, 102105","doi":"10.1016/j.bbrep.2025.102105","pmid":"40612001","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"LL-37 at 4 μM concentration enhanced rhinovirus-induced interferon-beta (IFNβ) expression in BEAS-2B human airway epithelial cells and reduced viral load. This enhancement did not involve upregulation of classical viral sensors (TLR3, MDA5, RIG-I). Instead, the effect was dependent on endosomal acidification (blocked by chloroquine) and critically required calcium — chelating calcium with EGTA abolished the response. LL-37 directly increased intracellular calcium concentration, and mimicking this calcium rise with the ionophore A23187 replicated the IFNβ enhancement, confirming that calcium is the key mediator.","whyItMatters":"LL-37 was already known to kill bacteria and viruses directly, but this study reveals an additional indirect mechanism: it boosts the cell's own antiviral alarm system (interferon production) through a calcium-dependent pathway. This adds a new dimension to how the body's innate immune peptides fight respiratory infections and could inform therapeutic strategies for enhancing antiviral defenses in the airways.","specificNumbers":"","methodology":"Human airway epithelial cells (BEAS-2B cell line) were infected with rhinovirus in the presence or absence of LL-37 (4 μM). IFNβ transcript levels were measured, along with viral load. Receptor expression (TLR3, MDA5, RIG-I) was assessed. Pharmacological inhibitors were used to probe mechanisms: chloroquine for endosomal acidification, EGTA for calcium chelation. Intracellular calcium was measured using the Fluo-4 AM fluorescent indicator. The calcium ionophore A23187 was used to confirm the calcium-dependent mechanism.","limitations":"The study used a single immortalized cell line (BEAS-2B), which may not fully represent primary airway epithelial cell behavior. All experiments were conducted in vitro with no animal or human data. Only one rhinovirus strain was tested. The LL-37 concentration used (4 μM) may or may not reflect physiological concentrations in the airways during infection. Long-term effects and potential cytotoxicity at this concentration were not assessed."},{"rthcId":"RPEP-10333","title":"Engineered Peptide Coacervates Enable Efficient Intracellular Delivery of the MYC Inhibitor omoMYC.","authors":"Cerrato, Carmine P; Krkoška, Martin; Sun, Yue; Liaño-Pons, Judit; Neo, Qi Ying; Vosselman, Thibault; Alzrigat, Mohammad; Vojtěšek, Borek; Lane, David P; Arsenian Henriksson, Marie; Miserez, Ali; Landreh, Michael","year":2025,"journal":"Molecular pharmaceutics, 22(6), 3479-3490","doi":"10.1021/acs.molpharmaceut.5c00468","pmid":"40304302","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10334","title":"Evaluating the impact of anti-CGRP monoclonal antibodies on retinal features in migraine patients: a retrospective optical coherence tomography study.","authors":"Cesareo, Massimo; Martucci, Alessio; Bovenzi, Roberta; Lombardo, Marco; Pistoia, Francesca; D'Agostino, Vittoria Carla; Stefani, Alessandro; Nucci, Carlo; Mercuri, Nicola Biagio; Albanese, Maria","year":2025,"journal":"Therapeutic advances in neurological disorders, 18, 17562864251347277","doi":"10.1177/17562864251347277","pmid":"40568185","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10335","title":"Reduction of New Onset of Atrial Fibrillation in Patients Treated with Semaglutide: An updated systematic review and meta regression analysis of randomized controlled trials.","authors":"Cesaro, Arturo; Pastori, Daniele; Acerbo, Vincenzo; Biccirè, Flavio Giuseppe; Golino, Michele; Panico, Domenico; Prati, Francesco; Abbate, Antonio; Lip, Gregory Y H; Calabrò, Paolo","year":2025,"journal":"European journal of preventive cardiology","doi":"10.1093/eurjpc/zwaf257","pmid":"40294206","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10336","title":"Utilization of Proteomic Measures for Early Detection of Drug Benefits and Adverse Effects.","authors":"Chadwick, Jessica; Berry, Colin; Carpenter, Meredith A; Gulati, Geeta; Heck, Siri Lagethon; Hinterberg, Michael A; Holman, Rury R; Lee, Matthew M Y; Omland, Torbjørn; Paterson, Clare; Petrie, Mark C; Sattar, Naveed; Shah, Svati H; Shrestha, Sama; Sourij, Harald; Troth, Emma V; Vinje, Victoria; Williams, Stephen A","year":2025,"journal":"Journal of clinical pharmacology, 65(11), 1460-1473","doi":"10.1002/jcph.70077","pmid":"40619592","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10337","title":"ENT1 inhibition enhances weight control and metabolic health in diet-induced obesity.","authors":"Chaible, Lucas; Preillon, Julie; Philippart, Charlotte; Canevat, Alizée; Saerens, Laura; Kondratow, Dimitri; Deligny, Michael; Goffaux, Alexis; Michaux, Anne-Catherine; Letellier, Marie-Claire; Rosewick, Nicolas; Carbonez, David; Marchante, João; Strozzi, Francesco; Houthuys, Erica; Marillier, Reece; McGrath, Yvonne; Van der Plas, Steven; Pfeifer, Alexander; Chesné, Julie","year":2025,"journal":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 193, 118848","doi":"10.1016/j.biopha.2025.118848","pmid":"41371040","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10338","title":"Real-world effectiveness of adding newer generation GLP-1RA to SGLT2i in type 2 diabetes.","authors":"Chaiyakunapruk, Nathorn; Tan, Xi; Liang, Yuanjie; Guevarra, Mico; Xie, Lin; Cheng, Alice Y Y","year":2025,"journal":"Cardiovascular diabetology, 24(1), 177","doi":"10.1186/s12933-025-02737-1","pmid":"40275332","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10339","title":"Corrin Ring Modification in Peptide Drug Development - a Brief History of \"Corrination\".","authors":"Cham, Nancy; Doyle, Robert P","year":2025,"journal":"ChemMedChem, 20(10), e202500129","doi":"10.1002/cmdc.202500129","pmid":"40082209","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10340","title":"Glucagon-like peptide and its receptor agonists for the treatment of rheumatic diseases.","authors":"Chamchoum, Elie; Katrib, Nadia; Nassif, Nicolas; Ratel, Yara; Rida, Mohamad Ali","year":2025,"journal":"World journal of experimental medicine, 15(3), 107020","doi":"10.5493/wjem.v15.i3.107020","pmid":"41523775","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10341","title":"Cost-utility analysis of eptinezumab for migraine prevention in Taiwan.","authors":"Chan, Cheng-Shen; Huang, Tzu-Yao; Tseng, Wei-Hsuan; Lin, Tsung-Kun; Yang, Fu-Chi; Liu, Yi; Ruan, Yuan-Zhen; Hsieh, Ping-Hsuan","year":2025,"journal":"Health economics review, 16(1), 11","doi":"10.1186/s13561-025-00711-x","pmid":"41455879","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10342","title":"Peptide receptor chemoradionuclide therapy for neuroendocrine neoplasms: A systematic review.","authors":"Chan, Dennis S; Kanagaratnam, Aran L; Pavlakis, Nick; Chan, David L","year":2025,"journal":"Journal of neuroendocrinology, 37(3), e13355","doi":"10.1111/jne.13355","pmid":"37987535","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10343","title":"Appendicitis After Initiation of Tirzepatide.","authors":"Chan, Garrett; Ansar, Mariam; Klein, Marlena","year":2025,"journal":"Diabetes, metabolic syndrome and obesity : targets and therapy, 18, 261-265","doi":"10.2147/DMSO.S496739","pmid":"39906694","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10344","title":"Psychological stress increases skin infection through the action of TGFβ to suppress immune-acting fibroblasts.","authors":"Chan, Hung; Li, Fengwu; Dokoshi, Tatsuya; Cavagnero, Kellen J; Li, Qing; Chen, Yang; Aguilera, Carlos; Nakatsuji, Teruaki; Liu, Edward; Indra, Aaryan; Yang, Daping; Valentina, Ottaviani; Numata, Tomofumi; Crown, Brittany; Li, Henry; Williams, Kevin J; Chiu, Isaac M; Bensinger, Steven J; Chen, WanJun; Gallo, Richard L","year":2025,"journal":"Science immunology, 10(106), eads0519","doi":"10.1126/sciimmunol.ads0519","pmid":"40215323","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10345","title":"Glucagon-Like Peptide-1 Receptor Agonists, Readmission, and Postoperative Complications in Arthroplasty: A Systematic Review and Meta-Analysis.","authors":"Chan, Yi-Chuan; Chuang, Shu-Han; Wu, Lien-Chen; Kuo, Yi-Jie; Lian, Yu-Zhi; Chen, Yu-Pin","year":2025,"journal":"The Journal of arthroplasty","doi":"10.1016/j.arth.2025.11.036","pmid":"41276236","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10346","title":"Hypotensive effect of potent angiotensin-I-converting enzyme inhibitory peptides from corn gluten meal hydrolysate: Gastrointestinal digestion and transepithelial transportation modifications.","authors":"Chanajon, Phiromya; Hamzeh, Ali; Tian, Fu; Roytrakul, Sittiruk; Oluwagunwa, Olayinka A; Kadam, Deepak; Aluko, Rotimi E; Aueviriyavit, Sasitorn; Wongwanakul, Ratjika; Yongsawatdigul, Jirawat","year":2025,"journal":"Food chemistry, 462, 140953","doi":"10.1016/j.foodchem.2024.140953","pmid":"39216374","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10347","title":"Clinical Outcomes of 177Lu-DOTATATE Peptide Receptor Radionuclide Therapy in Patients with Skeletal Metastases from Neuroendocrine Tumors: Insights from Real-World Experience.","authors":"Chandekar, Kunal Ramesh; Satapathy, Swayamjeet; Ballal, Sanjana; Yadav, Madhav Prasad; Ravindra, Shubha Gadde; Rastogi, Sameer; Sahoo, Ranjit Kumar; Bal, Chandrasekhar","year":2025,"journal":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 66(7), 1046-1053","doi":"10.2967/jnumed.125.269456","pmid":"40404399","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10348","title":"Perch Hydrolysates from Upcycling of Perch Side Streams Accelerate Wound Healing by Enhancing Fibroblasts to Secrete Procollagen I, Fibronectin, and Hyaluronan.","authors":"Chang, Jia-Feng; Hsieh, Chih-Yu; Chen, Ling-Ni; Lee, Mao-Hsiang; Ting, Yi-Han; Yang, Chi-Yu; Lin, Chih-Cheng","year":2025,"journal":"Current issues in molecular biology, 47(1)","doi":"10.3390/cimb47010057","pmid":"39852171","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Perch hydrolysates contained 62.60% peptides with low molecular weight (≤1 kDa), with collagen composition at 1,183 mg/100g and branched-chain amino acids at 1,122 mg/100g. The peptide sequence FPSLVRGP, at 6.21% abundance, was identified as potentially antihypertensive.\n\nIn fibroblast models, the peptides accelerated wound healing by increasing secretion of procollagen I, fibronectin, and hyaluronan. In SD rats with wounds mimicking human injuries, orally administered perch hydrolysates (MW <2.3 kDa) accelerated wound healing through the combined action of collagen-forming amino acids, branched-chain amino acids, and matrikines (extracellular matrix-derived signaling peptides).","whyItMatters":"Wound healing remains a significant medical challenge, especially for chronic wounds in aging or diabetic populations. This study demonstrates that fish processing waste — typically discarded — can yield bioactive peptides with wound-healing properties. If developed as dietary supplements, these could provide an accessible, sustainable approach to supporting wound repair while simultaneously addressing food waste in the fishing industry.","specificNumbers":"","methodology":"Perch side streams (processing waste) were hydrolyzed using a commercial enzyme complex with proprietary pressure extraction. Peptide molecular weight distribution and amino acid composition were characterized. Wound healing effects were tested in two models: human fibroblast cell cultures (measuring procollagen I, fibronectin, and hyaluronan secretion) and an SD rat wound model with oral administration of the hydrolysates.","limitations":"The rat wound model, while useful, may not fully predict human wound-healing responses. The study used oral administration, and the bioavailability and mechanism of action of the peptides after oral intake are not fully characterized. The specific peptide FPSLVRGP's antihypertensive effect was suggested based on sequence similarity rather than direct testing. Exact dosing and duration in the rat model are not specified in the abstract."},{"rthcId":"RPEP-10349","title":"Structures, antioxidant, and angiotensin I-converting enzyme (ACE)-inhibitory activities of peptides derived from protein hydrolysates of three phenolics-rich legume genera.","authors":"Chang, Sam K C; Zhang, Yan; Pechan, Tibor","year":2025,"journal":"Journal of food science, 90(2), e70069","doi":"10.1111/1750-3841.70069","pmid":"39980267","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"After simulated digestion and purification, peptides from all three legumes showed potent ACE-inhibitory activity. The IC50 values (concentration needed to block 50% of ACE activity) improved two- to nine-fold after gel-permeation chromatography purification, reaching approximately 85 µg/mL for lentil, 64 µg/mL for black soybean, and 93 µg/mL for black turtle bean.\n\nA total of 210 peptides were sequenced from the small (<3 kDa) fractions, with chain lengths from 6 to 18 amino acids. Lentil had the shortest average peptide length at 7.7 amino acids. Overall, the bioactive peptides contributed more antioxidant capacity and ACE inhibition than the phenolic compounds in these legumes. Black turtle bean proteins required more heating to achieve comparable digestibility to lentil and soy proteins.","whyItMatters":"ACE inhibitors are among the most prescribed blood pressure medications worldwide. Finding natural ACE-inhibiting peptides in common foods like lentils and beans suggests dietary protein — not just phenolics or fiber — may contribute to the cardiovascular benefits of legume-rich diets. This research supports the development of functional foods and supplements based on legume-derived bioactive peptides.","specificNumbers":"","methodology":"Proteins were isolated from lentils, black soybeans, and black turtle beans, then cooked and digested in vitro using pepsin, trypsin, and chymotrypsin to simulate human digestion. The resulting peptides were separated by ultrafiltration, anion-exchange chromatography, and gel-permeation chromatography. Peptides under 3 kDa were sequenced, and their antioxidant and ACE-inhibitory activities were measured at each purification step.","limitations":"This is entirely an in vitro study — proteins were digested in a lab, not in actual human stomachs. Real digestion involves variable pH, enzyme levels, and transit times that could produce different peptide profiles. The ACE inhibition was measured in a test tube, not as blood pressure reduction in living organisms. Whether these peptides survive intestinal absorption intact and reach the bloodstream in active form is unknown."},{"rthcId":"RPEP-10350","title":"Chronic semaglutide treatment enhances the incentive motivational value of a small food reward and associated cue in male and female rats.","authors":"Chang, Stephen E; Turner, Christopher A; Pagán, Natalia Morales; Pereira, Daniela; Kleer, Sophia; Flagel, Shelly B","year":2025,"journal":"bioRxiv : the preprint server for biology","doi":"10.64898/2025.12.06.692775","pmid":"41415399","tags":[],"studyType":"animal-study","evidenceStrength":"low-moderate","keyFinding":"Chronic semaglutide treatment in rats created a surprising split in behavior: while it reduced overall food consumption (both free food reward and regular chow), it actually increased the motivational value of limited food rewards and food-associated cues. Semaglutide-treated rats worked harder on a progressive ratio schedule to earn food and responded more for a food-paired cue during conditioned reinforcement testing.\n\nImportantly, semaglutide did not alter the acquisition or expression of Pavlovian conditioned approach behavior itself. The dissociation — eating less overall but wanting food more intensely when it's limited — suggests semaglutide doesn't simply suppress all food motivation but rather reshapes the relationship between reward value and availability.","whyItMatters":"This challenges the simple narrative that GLP-1 drugs just reduce appetite. While semaglutide clearly decreases how much rats eat when food is freely available, it simultaneously amplifies how motivating a small, limited food reward becomes. This has implications for understanding why some patients on GLP-1 drugs may still experience intense food cravings in certain contexts, and how these drugs interact with the brain's reward system.","specificNumbers":"Chronic administration · male and female rats · enhanced conditioned reinforcement responding · increased progressive ratio responding · reduced free food consumption · reduced chow intake","methodology":"Researchers chronically administered semaglutide to male and female rats and assessed behavior using Pavlovian conditioned approach (PavCA), conditioned reinforcement tests, progressive ratio schedules for food reward, and ad libitum food consumption measures. Vehicle-treated rats served as controls.","limitations":"This is a preprint (bioRxiv) that has not yet undergone peer review. The study was conducted in rats, and the translation of incentive salience measures to human food motivation is uncertain. Specific dosing details and sample sizes are not provided in the abstract."},{"rthcId":"RPEP-10351","title":"In-depth analysis of the tear fluid glycoproteome reveals diverse lacritin glycosylation and spliceoforms.","authors":"Chang, Vincent; Mahoney, Keira E; Lian, Isaac; Chen, Ryan; Chung, Nara; Paaske Utheim, Tor; Karlsson, Niclas G; Malaker, Stacy A","year":2025,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2025.06.13.659589","pmid":"40667337","tags":["antimicrobial-peptides","biomarkers","proteomics"],"studyType":"Basic Science (Analytical/Proteomics)","evidenceStrength":"Preliminary","keyFinding":"Researchers conducted the first comprehensive mapping of sugar modifications (glycosylation) on proteins in human tear fluid, with a focus on lacritin — a protein critical for tear production, immune defense, and antimicrobial activity. They identified 19 specific sites where sugar chains attach to lacritin, and found that these glycans make up over 50% of the protein's molecular weight and make its structure rigid and extended.\n\nUsing AlphaFold 3.0 modeling, they visualized how these sugar modifications shape the protein's 3D structure. They also discovered two previously undetected splice variants of lacritin and characterized the glycosylation of other tear proteins including immunoglobulin A (IgA) and lactoferrin — both of which have antimicrobial properties and serve as disease biomarkers.","whyItMatters":"Tear fluid contains antimicrobial proteins and peptides that serve as the eye's first line of defense against infection. Understanding the precise sugar modifications on these proteins matters because glycosylation directly affects protein folding, stability, and biological function. Changes in lacritin or lactoferrin glycosylation could be linked to dry eye disease, infection susceptibility, or other ocular conditions — and could serve as non-invasive diagnostic biomarkers collected from tears.","specificNumbers":"19 O-glycosites identified on lacritin · glycans = >50% of lacritin molecular weight · 2 lacritin spliceoforms detected · IgA + lactoferrin glycosylation characterized · AlphaFold 3.0 + GlycoShape modeling","methodology":"The researchers used mass spectrometry to perform the first O-glycoproteomic analysis of human tear fluid. They mapped glycosylation sites on lacritin and other tear proteins, identified glycan structures at each site, and detected protein spliceoforms. AlphaFold 3.0 and GlycoShape were used to model the structural impact of glycosylation on lacritin's 3D conformation.","limitations":"This is a preprint (bioRxiv) that has not yet undergone peer review. The study characterizes glycosylation patterns but does not directly test how specific glycan changes affect lacritin's antimicrobial or tear-stimulating functions. The sample size and donor demographics are not described in the abstract. Correlations with ocular diseases are proposed but not tested. The structural modeling is computational and has not been experimentally validated."},{"rthcId":"RPEP-10352","title":"α6GABAA receptor positive allosteric modulators targeting trigeminal ganglia for preventing and aborting chronic periorbital allodynia and cephalic pain in both sexes: A mechanistic and comparative preclinical study.","authors":"Chang, Xin-Chen; Yeh, Chen-Jiun; Pan, Yi-Ting; Chen, Yueh-Peng; Sharmin, Dishary; Cook, James; Pei, Yu-Cheng; Chiou, Lih-Chu","year":2025,"journal":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 189, 118344","doi":"10.1016/j.biopha.2025.118344","pmid":"40652726","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10353","title":"Association of GLP-1 Receptor Agonist Use With Risk of Lumbar Degenerative Disease and Spine Surgery in Patients With Type 2 Diabetes: A Propensity Score-matched Cohort Study.","authors":"Chang, Yu; Chi, Kuan-Yu; Song, Junmin; Chen, Chien-Min; Lin, Hong-Min","year":2025,"journal":"Global spine journal, 21925682251383170","doi":"10.1177/21925682251383170","pmid":"40988481","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10354","title":"The impact of semaglutide on fusion rates following posterior lumbar fusion surgery in patients with type 2 diabetes.","authors":"Chang, Yu; Lin, Hong-Min; Chi, Kuan-Yu; Song, Junmin; Atwan, Hany","year":2025,"journal":"International journal of surgery (London, England), 111(7), 4898-4900","doi":"10.1097/JS9.0000000000002492","pmid":"40434727","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10355","title":"AI/ML-empowered approaches for predicting T Cell-mediated immunity and beyond.","authors":"Chao, Cheng-Chi; Chiu, Yulun; Yeung, Lucas; Yee, Cassian; Jiang, Chongming; Shen, Xiling","year":2025,"journal":"Frontiers in immunology, 16, 1651533","doi":"10.3389/fimmu.2025.1651533","pmid":"40948755","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10356","title":"Hibiscus syriacus L. Exhibits Cardioprotective Activity via Anti-Inflammatory and Antioxidant Mechanisms in an In Vitro Model of Heart Failure.","authors":"Chao, Hung-Hsin; Cheng, Tzu-Hurng; Chen, Chun-Chao; Liu, Ju-Chi; Chen, Jin-Jer; Sung, Li-Chin","year":2025,"journal":"Life (Basel, Switzerland), 15(8)","doi":"10.3390/life15081229","pmid":"40868877","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10357","title":"Deepstack-ACE: A deep stacking-based ensemble learning framework for the accelerated discovery of ACE inhibitory peptides.","authors":"Charoenkwan, Phasit; Chumnanpuen, Pramote; Schaduangrat, Nalini; Shoombuatong, Watshara","year":2025,"journal":"Methods (San Diego, Calif.), 234, 131-140","doi":"10.1016/j.ymeth.2024.12.005","pmid":"39709069","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10358","title":"Inflammation: The Mother of All Diseases Meets the Mother of All Therapies.","authors":"Chatanaka, Miyo K; Diamandis, Eleftherios P","year":2025,"journal":"EJIFCC, 36(3), 236-243","doi":null,"pmid":"41098220","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10359","title":"Current status of Liraglutide delivery systems for the management of type 2 diabetes mellitus.","authors":"Chatterjee, Riti; Galave, Vishal Sangita Babasaheb; Jindal, Anil B","year":2025,"journal":"Drug delivery and translational research, 15(12), 4479-4500","doi":"10.1007/s13346-025-01965-y","pmid":"40914786","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10360","title":"An efficient method for site-selective boronation of peptides and proteins applied in magnified bacterial imaging.","authors":"Chatterjee, Saurav; Chowdhury, Arnab; Verma, Neelam; Basa, Sneha; Tripathi, Nitesh Mani; Gour, Vinod; Rai, Vishal; Bandyopadhyay, Anupam","year":2025,"journal":"Nature communications, 17(1), 454","doi":"10.1038/s41467-025-67141-5","pmid":"41381458","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10361","title":"Structural and Computational Insights into the Angiotensin II Type 1 Receptor: Advances in Antagonist Design and Implications for Hypertension Therapy (2020-2024).","authors":"Chatzipieris, Filippos Panteleimon; Petsas, Errikos; Lambrinidis, George; Matsoukas, John M; Mavromoustakos, Thomas","year":2025,"journal":"Biomolecules, 16(1)","doi":"10.3390/biom16010020","pmid":"41594562","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identified three categories of AT1R antagonists investigated from 2020 to 2024: large peptide molecules, small non-peptide-like molecules, and sartan derivatives. Notably, some non-sartan compounds exhibited very low IC50 values (indicating high potency), demonstrating that there is substantial chemical space beyond current drug classes that could yield more effective antihypertensive medications.\n\nComputational chemistry analysis revealed the key molecular interactions governing binding affinity at the AT1R active site, explaining why structurally diverse compounds show different potencies. The review also updated understanding of AT1R structure-function relationships based on recent cryo-EM and crystallographic data.","whyItMatters":"Hypertension affects over 1.2 billion people globally and is the leading modifiable risk factor for cardiovascular disease. While existing sartans (ARBs) are effective, many patients don't achieve adequate blood pressure control. Discovering new chemical classes of AT1R antagonists — particularly those with higher potency or different pharmacological profiles — could lead to better treatments for resistant hypertension and provide alternatives for patients who don't respond well to current options.","specificNumbers":"","methodology":"This is a comprehensive literature review covering 2020–2024 publications on AT1R structure, function, and inhibitor design. The authors supplemented the literature analysis with their own computational chemistry studies — molecular docking and binding energy calculations — to identify key interactions between diverse antagonist molecules and the AT1R binding site. In vitro and in vivo potency data from published studies were compared across compound classes.","limitations":"This is a narrative review without systematic methodology or meta-analysis. The computational modeling is supplementary and reflects the authors' specific docking protocols. Many of the novel compounds reviewed are in early preclinical stages with no clinical data. The comparison across different studies with varying assay conditions limits direct potency comparisons."},{"rthcId":"RPEP-10362","title":"From sea to supplement: Algal protein extraction methods and functional benefits.","authors":"Chaudhary, Shreya; Singh, Rakhi; Mishra, Shivangi; Talwar, Binanshu; Balhara, Kunal","year":2025,"journal":"International journal of biological macromolecules, 328(Pt 2), 147750","doi":"10.1016/j.ijbiomac.2025.147750","pmid":"40972918","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10363","title":"Cortical thickness studies in migraine: Current evidence and future directions.","authors":"Chaudhry, Basit Ali; Younis, Samaira; Messina, Roberta; García-Azorín, David; Karsan, Nazia; Coppola, Gianluca; Christensen, Rune Häckert; Al-Karagholi, Mohammad Mahdi; Pozo-Rosich, Patricia; Amin, Faisal Mohammad","year":2025,"journal":"Cephalalgia : an international journal of headache, 45(6), 3331024251341204","doi":"10.1177/03331024251341204","pmid":"40474701","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10364","title":"Sequencing Choices and Real-World Clinical Management in Advanced Grade 2/3 GEP-NET Treatment: The Emerging Role of PRRT.","authors":"Chauhan, Aman; Halfdanarson, Thorvardur R; Vijayvergia, Namrata","year":2025,"journal":"Cancers, 17(18)","doi":"10.3390/cancers17183008","pmid":"41008852","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10365","title":"Multifaceted role and regulation of neuropeptide Y in the ovary of wall lizard, Hemidactylus flaviviridis.","authors":"Chauhan, Vishesh; Rai, Umesh; Tripathy, Mamta; Kumar, Sunil","year":2025,"journal":"General and comparative endocrinology, 371, 114772","doi":"10.1016/j.ygcen.2025.114772","pmid":"40543819","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10366","title":"Neuropeptide Y at the crossroads of male reproductive functions in a seasonally breeding reptile, Hemidactylus flaviviridis.","authors":"Chauhan, Vishesh; Rai, Umesh; Tripathy, Mamta; Kumar, Sunil","year":2025,"journal":"Comparative biochemistry and physiology. Part A, Molecular & integrative physiology, 303, 111826","doi":"10.1016/j.cbpa.2025.111826","pmid":"39971152","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10367","title":"The neurobiological impact of oxytocin in mental health disorders: a comprehensive review.","authors":"Chaulagain, Ram Prasad; Shrestha, Yelona; Shrestha, Harisharan; Bhandari, Rameshor; Gurung, Praful","year":2025,"journal":"Annals of medicine and surgery (2012), 87(3), 1479-1486","doi":"10.1097/MS9.0000000000003015","pmid":"40213210","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10368","title":"Oral delivery of protein and peptide therapeutics.","authors":"Chavda, Vivek P; Balar, Pankti C","year":2025,"journal":"Progress in molecular biology and translational science, 212, 355-387","doi":"10.1016/bs.pmbts.2024.11.003","pmid":"40122651","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10369","title":"Analytical and drug delivery strategies for short peptides: From manufacturing to market.","authors":"Chawathe, Ashwini; Ahire, Vishal; Luthra, Kshitiz; Patil, Bhumika; Garkhal, Kalpna; Sharma, Nitish","year":2025,"journal":"Analytical biochemistry, 696, 115699","doi":"10.1016/j.ab.2024.115699","pmid":"39461693","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10370","title":"Two-dimensional profiling and peptide sequencing of angiotensin-I converting enzyme (ACE) inhibitory proteolysate from winged bean (Psophopcarpus tetragonolobus) seeds.","authors":"Chay, Shyan Yea; Brishti, Fatema Hossain; Auwal, Shehu Muhammad; Abdul Kari, Zulhisyam; Roslan, Nurdiyana Aqilah; Wong, Clement Kiing Fook; Saari, Nazamid","year":2025,"journal":"Analytical methods : advancing methods and applications, 17(22), 4627-4638","doi":"10.1039/d4ay02073a","pmid":"40408140","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Papain hydrolysis of winged bean seed protein produced ACE-inhibitory fractions. Three key subfractions were identified: F-12-12 (87.8% ACE inhibition, pI 10.0), F-16-6 (77.3% inhibition, pI 6.8), and F-16-2 (50.1% inhibition, pI 3.6). Sequencing identified 11 peptides via database search and 4 via de novo sequencing, totaling 15 unique ACE-inhibitory peptides. All were oligopeptides of 4-15 amino acid residues with molecular weights of 489.9-1656.7 Da (all <2 kDa).","whyItMatters":"Finding new sustainable sources of bioactive peptides is important for both global nutrition and cardiovascular health. Winged bean grows in tropical regions where hypertension is a major health burden but access to pharmaceutical ACE inhibitors may be limited. Developing winged bean-based functional foods or supplements could provide affordable, locally sourced blood pressure support while promoting cultivation of this underutilized but highly nutritious crop.","specificNumbers":"","methodology":"Winged bean seeds were enzymatically hydrolyzed with papain. The hydrolysate was separated by reverse-phase HPLC followed by isoelectric focusing. ACE-inhibitory activity was measured for each fraction. Selected active fractions were sequenced using LC-MS/MS. Peptides were identified through database matching and de novo sequencing, with structural analysis confirming ACE-inhibitory properties.","limitations":"This is entirely an in vitro study — no cell culture, animal, or human studies were performed. ACE inhibition in a test tube doesn't guarantee blood pressure effects in vivo. The peptides' stability during gastrointestinal digestion and their absorption potential were not tested. Only papain was used as the hydrolysis enzyme; other enzymes might yield different peptides. The winged bean variety and growing conditions could affect results."},{"rthcId":"RPEP-10371","title":"Calcitonin gene-related peptide monoclonal antibody treatment for new daily persistent headache.","authors":"Cheema, Sanjay; Rantell, Khadija Rerhou; Pickering, Rachel; Lagrata, Susie; Kamourieh, Salwa; Matharu, Manjit","year":2025,"journal":"The journal of headache and pain, 26(1), 170","doi":"10.1186/s10194-025-02111-2","pmid":"40721729","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10372","title":"A meticulous biocompatibility and toxicological assessment of a self-assembling peptide nanofiber-nanoceramic biomimetic nanocomposite, per ISO 10993 guidelines.","authors":"Chegeni, Solmaz; Tavakol, Hani; Rezayat, Seyed Mahdi; Tavakol, Shima","year":2025,"journal":"Nanotoxicology, 19(5), 489-507","doi":"10.1080/17435390.2025.2538479","pmid":"40746284","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The peptide nanofiber-nanoceramic composite passed all ISO 10993 biocompatibility evaluations conducted by IFDA laboratories. Specific results included: non-cytotoxic with no significant reduction in cell viability, acceptable hemolytic activity in blood compatibility testing, no evidence of DNA damage in genotoxicity assays, no irritation or sensitization reactions, and no adverse clinical signs, weight changes, or organ pathologies in systemic toxicity studies in mice.\n\nIn the bone regeneration study in rabbits, the material demonstrated complete and osteoinductive bone formation over one month. The self-assembling peptide nanofibers (15-20 nm) contribute osteogenic, angiogenic, and immunomodulatory properties while mimicking extracellular matrix architecture. The spherical nanohydroxyapatite (30-45 nm) and tricalcium phosphate provide the mineral component with optimized particle size, morphology, and pH stability for vascularized bone formation.","whyItMatters":"Bone grafts are needed for millions of fractures, dental implants, and reconstructive surgeries annually, but no commercial product fully replicates bone's complex nanoscale structure. This peptide-ceramic composite is one of the first to pass comprehensive regulatory-grade safety testing while demonstrating actual bone regeneration capability. If it reaches clinical use, it could offer a superior alternative to current synthetic bone grafts.","specificNumbers":"","methodology":"The nanocomposite was evaluated following ISO 10993 international standards for biological evaluation of medical devices. Testing included in vitro assays (cytotoxicity, genotoxicity, hemocompatibility) and in vivo studies (sensitization and irritation in animal models, acute and chronic systemic toxicity in mice, and bone regeneration assessment in rabbits over one month). All biocompatibility testing was conducted by IFDA laboratories.","limitations":"The bone regeneration study was conducted in rabbits over only one month, and long-term durability and remodeling were not assessed. Animal bone healing differs from human healing in speed and biology. The study does not report specific sample sizes for animal experiments. No comparison with commercially available bone graft materials was described. Human clinical trials would be needed before this material could be used in patients."},{"rthcId":"RPEP-10373","title":"Treating Sarcopenic Obesity in the Era of Incretin Therapies: Perspectives and Challenges.","authors":"Chen, Alissa S; Batsis, John A","year":2025,"journal":"Diabetes, 74(12), 2179-2190","doi":"10.2337/dbi25-0004","pmid":"40644314","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10374","title":"Novel peptide inhibitor of matrix Metalloproteinases-1 from pufferfish skin collagen hydrolysates and its potential Photoprotective activity via the MAPK/AP-1 signaling pathway.","authors":"Chen, Bei; Cai, Shuilin; Cui, Lulu; Yu, Ting; Qiao, Kun; Su, Yongchang; Xu, Min; Tang, Haiyan; Liu, Shuji; Yang, Ming; Liu, Zhiyu","year":2025,"journal":"Journal of photochemistry and photobiology. B, Biology, 262, 113088","doi":"10.1016/j.jphotobiol.2024.113088","pmid":"39732112","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10375","title":"Efficacy and safety of combination of semaglutide and basal insulin in patients with of type 2 diabetes mellitus: A systematic review and meta-analysis.","authors":"Chen, Binbin; Tao, Lanqiu; Tian, Min; Ji, Zhaohua","year":2025,"journal":"Clinical nutrition ESPEN, 66, 564-572","doi":"10.1016/j.clnesp.2025.01.056","pmid":"39892787","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10376","title":"Membrane-active peptides for anticancer therapies.","authors":"Chen, Charles H","year":2025,"journal":"Progress in molecular biology and translational science, 212, 67-116","doi":"10.1016/bs.pmbts.2024.10.005","pmid":"40122653","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10377","title":"A SARS-CoV-2 spike-derived adjuvant peptide boosts IL-17/IFN-γ immunity and improves anti-PD-L1 therapy against melanoma.","authors":"Chen, Chia-Hung; Weng, Tzu-Han; Kuo, Ta-Wei; Huang, Kai-Yao; Chen, Yu-Chi; Huang, Hsiao-Hsuan; Kao, Hui-Ju; Yu, Chen-Lin; Huang, Chen-Chen; Weng, Shun-Long; Liao, Kuang-Wen","year":2025,"journal":"Molecular medicine (Cambridge, Mass.), 31(1), 338","doi":"10.1186/s10020-025-01384-2","pmid":"41455906","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10378","title":"Effects of combined metformin and semaglutide therapy on body weight, metabolic parameters, and reproductive outcomes in overweight/obese women with polycystic ovary syndrome: a prospective, randomized, controlled, open-label clinical trial.","authors":"Chen, Haiyan; Lei, Xiaohui; Yang, Zhuoran; Xu, Yuxin; Liu, Dongfang; Wang, Cong; Du, Hu","year":2025,"journal":"Reproductive biology and endocrinology : RB&E, 23(1), 108","doi":"10.1186/s12958-025-01447-3","pmid":"40713699","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10379","title":"Food-Derived Tripeptide-Copper Self-Healing Hydrogel for Infected Wound Healing.","authors":"Chen, Han; Yang, Pu; Xue, Ping; Li, Songjie; Dan, Xin; Li, Yang; Lei, Lanjie; Fan, Xing","year":2025,"journal":"Biomaterials research, 29, 0139","doi":"10.34133/bmr.0139","pmid":"39902373","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The composite hydrogel (EW/OKGM@GHK-Cu, or GEK) combined oxidized konjac glucomannan and egg white proteins cross-linked via Schiff base chemistry, loaded with the bioactive copper peptide GHK-Cu. The hydrogel demonstrated self-healing capability, meaning it could repair itself after damage.\n\nThe GEK dressing exhibited multiple therapeutic properties: antibacterial activity, anti-inflammatory effects, hemostatic function through tissue adhesion, and promotion of neovascularization (new blood vessel formation). These combined properties made it effective for skin regeneration in infected wound models, positioning it as a comprehensive wound management solution derived entirely from natural food sources.","whyItMatters":"GHK-Cu is one of the most studied bioactive peptides for tissue repair, but delivering it effectively to wound sites has been a challenge. By embedding GHK-Cu in a self-healing hydrogel made from natural materials, this study solves the delivery problem while adding the hydrogel's own beneficial properties (moisture maintenance, tissue adhesion, antibacterial action). The all-natural composition could make this approach both effective and affordable for clinical use in wound management.","specificNumbers":"","methodology":"Researchers extracted oxidized konjac glucomannan (OKGM) from konjac and proteins from fresh egg white (EW). These were combined into a self-repairing hydrogel through Schiff base cross-linking. The copper peptide GHK-Cu was loaded into the hydrogel matrix. The resulting GEK hydrogel was characterized for self-healing properties, biocompatibility, and degradability. Its antibacterial, anti-inflammatory, hemostatic, and wound-healing properties were evaluated, including assessment of neovascularization and skin regeneration.","limitations":"The abstract does not specify whether the wound healing data comes from in vitro, animal, or human studies (though the claims suggest at least preclinical testing). Specific quantitative results (wound closure rates, bacterial kill percentages, comparison to standard dressings) are not provided. The GHK-Cu release kinetics from the hydrogel are not described. Long-term stability and shelf life are not addressed. Clinical translation from laboratory to human use requires extensive further testing."},{"rthcId":"RPEP-10380","title":"Helicobacter pylori infection impairs glucose homeostasis through gut microbiota dysbiosis.","authors":"Chen, Han; Wang, Zi; Su, Wei; Li, Shuo; Ye, Qiang; Zhang, Guoxin; Zhou, Xiaoying","year":2025,"journal":"BMC microbiology, 25(1), 663","doi":"10.1186/s12866-025-04402-9","pmid":"41087864","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10381","title":"Post-marketing safety monitoring of tirzepatide: a pharmacovigilance study based on the FAERS database.","authors":"Chen, Han; Ding, Yuhang; Shan, Yongqi","year":2025,"journal":"Expert opinion on drug safety, 24(8), 959-967","doi":"10.1080/14740338.2025.2468860","pmid":"40037695","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10382","title":"Pharmacovigilance analysis of neurological adverse events associated with GLP-1 receptor agonists based on the FDA Adverse Event Reporting System.","authors":"Chen, He; Liu, Sixing; Gao, Shuai; Shi, Hangyu; Yan, Yan; Xu, Yixing; Fang, Jiufei; Wang, Weiming; Chen, Huan; Liu, Zhishun","year":2025,"journal":"Scientific reports, 15(1), 18063","doi":"10.1038/s41598-025-01206-9","pmid":"40413246","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across six GLP-1 receptor agonists (exenatide, liraglutide, lixisenatide, dulaglutide, semaglutide, and tirzepatide), 19 distinct neurological adverse event signals were identified from 28,953 reports in the FAERS database spanning 2005–2024.\n\nThe most notable signals included dizziness, tremor, dysgeusia (taste distortion), lethargy, taste disorder, presyncope (near-fainting), parosmia (smell distortion), allodynia (pain from normally non-painful touch), and hypoglycemic unconsciousness.\n\nTime-to-onset analysis showed a median latency of 32 days (IQR 7–122 days), with 45.28% of neurological events occurring within the first 30 days of treatment initiation. These signals were confirmed across multiple statistical methods including reporting odds ratios, proportional reporting ratios, information components, and empirical Bayes geometric means.","whyItMatters":"With tens of millions of people now taking GLP-1 drugs for weight loss and diabetes, understanding their neurological safety profile is critical. This is the largest pharmacovigilance study to systematically catalog neurological side effects across all six approved GLP-1 receptor agonists, giving doctors a clearer picture of what to watch for — especially in the crucial first month of treatment.","specificNumbers":"","methodology":"The researchers analyzed the FDA Adverse Event Reporting System (FAERS) database from Q2 2005 through Q3 2024. They used a statistical approach called disproportionality analysis, which compares how often a side effect is reported with a specific drug versus all other drugs. They applied four different statistical methods to confirm their findings, and also analyzed how quickly after starting the drug each neurological event appeared.","limitations":"The FAERS database relies on voluntary reporting, which means side effects may be underreported or overreported. The data can't prove that GLP-1 drugs actually caused these neurological events — only that they were reported together. Confounding factors like other medications, underlying conditions, and the demographics of who reports aren't fully controlled for. The analysis also can't determine how common these events actually are in the overall population taking these drugs."},{"rthcId":"RPEP-10383","title":"The Therapeutic Effects of Semaglutide in Congenital Linear Scleroderma.","authors":"Chen, Helen; Elhawi, Mary; Tarbox, Michelle","year":2025,"journal":"Cureus, 17(7), e88725","doi":"10.7759/cureus.88725","pmid":"40861533","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10384","title":"Migraine.","authors":"Chen, Henry H; Heath, Kelly M; Patel, Palak R","year":2025,"journal":"Physical medicine and rehabilitation clinics of North America, 36(4), 701-714","doi":"10.1016/j.pmr.2025.08.002","pmid":"41167851","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10385","title":"Food-derived bioactive peptides: health benefits, structure‒activity relationships, and translational prospects.","authors":"Chen, Hongda; Sun, Jiabei; Fang, Haolie; Lin, Yuanyuan; Wu, Han; Lin, Dongqiang; Yang, Zhijian; Zhou, Quan; Zhao, Bingxiang; Zhou, Tianhua; Wu, Jianping; Li, Shanshan; Liu, Xiangrui","year":2025,"journal":"Journal of Zhejiang University. Science. B, 26(11), 1037-1058","doi":"10.1631/jzus.B2400106","pmid":"41276472","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10386","title":"Intestinal Neuroimmunology and Its Implications in Food Allergy.","authors":"Chen, Hongjie; Yang, Jing","year":2025,"journal":"Clinical reviews in allergy & immunology, 68(1), 76","doi":"10.1007/s12016-025-09090-x","pmid":"40753133","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10387","title":"Hepatocyte growth factor and B-type natriuretic peptide as independent predictors of mortality in HFpEF patients.","authors":"Chen, Hou-Liang; Zhu, Xue-Tao; Zhang, Wang; Cheng, Xiao-Bing; Hu, Ze-Ping","year":2025,"journal":"Frontiers in cardiovascular medicine, 12, 1512411","doi":"10.3389/fcvm.2025.1512411","pmid":"40041176","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10388","title":"Cardio-renal outcomes in type 2 diabetes patients with advanced chronic kidney disease on SGLT2 inhibitors or GLP-1 receptor agonists.","authors":"Chen, Jia-Jin; Tsai, Ming-Hsien; Ho, Wen-Yu; Fang, Yu-Wei; Chen, Meng-Ting; Hsiao, Ching-Chung","year":2025,"journal":"The American journal of medicine","doi":"10.1016/j.amjmed.2025.12.011","pmid":"41419094","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10389","title":"Investigation of vasoactive intestinal peptide expression and significance in a congenital diaphragmatic hernia animal model.","authors":"Chen, Jiajun; Xu, Huijiao; Yang, Li; Chen, Feifan; Li, Kunpeng; Xu, Bing; Liu, Wenying; Hou, Fang","year":2025,"journal":"Pediatric surgery international, 42(1), 31","doi":"10.1007/s00383-025-06257-7","pmid":"41342973","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10390","title":"Chromosome-Scale Genome Assembly and Genome-Wide Identification of Antimicrobial Peptide-Containing Genes in the Endangered Long-Finned Gudgeon Fish (Rhinogobio ventralis).","authors":"Chen, Jieming; Zhang, Xinhui; Li, Yanping; Lv, Yunyun; You, Xinxin; Shi, Qiong; Wen, Zhengyong","year":2025,"journal":"Biology, 14(11)","doi":"10.3390/biology14111486","pmid":"41300277","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10391","title":"Impact of GLP-1 Receptor Agonists on Suicide Behavior: A Meta-Analysis Based on Randomized Controlled Trials.","authors":"Chen, Jingqi; Zhang, Qiufeng; Wu, Qingping; Zhang, Xiaoming; Xiang, Zhiyi; Zhu, Sidong; Dai, Tianfu; Si, Yuexiu","year":2025,"journal":"Journal of diabetes, 17(9), e70151","doi":"10.1111/1753-0407.70151","pmid":"40887719","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10392","title":"Bifidobacterium longum subsp. longum B-53 Alleviated Abnormalities of Glycolipid Metabolism and Oxidative Stress in T2DM Mice Through Regulating Gut Microbiota and GLP-1 Secretion.","authors":"Chen, Jingru; Zhang, Linfang; Cheng, Zhiliang; Zhang, Yulong; Li, Xinyi; Zheng, Suo; Zhang, Ning; Li, Bailiang; Liu, Fei; Jiao, Yuehua","year":2025,"journal":"Journal of agricultural and food chemistry, 73(38), 24169-24186","doi":"10.1021/acs.jafc.5c07346","pmid":"40928360","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10393","title":"Discovery of peptide quality markers for quality control and identification of toad venom using LC-MS/MS and label-free methods.","authors":"Chen, Juan; Xue, Fei; Xie, Yingying; Cui, Weiliang; Tan, Lejun; Niu, Yan; Shi, Li; Wang, Lin; Liu, Li; Wang, Bing; Jiao, Yang; Lin, Yongqiang","year":2025,"journal":"Journal of chromatography. B, Analytical technologies in the biomedical and life sciences, 1254, 124504","doi":"10.1016/j.jchromb.2025.124504","pmid":"39923613","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10394","title":"Comprehensive safety analysis of adverse events associated with eptinezumab in migraine treatment.","authors":"Chen, Junchen; Huang, Shunqiu; Chen, Yashi; Luo, Cheng; Li, Yong","year":2025,"journal":"Scientific reports, 15(1), 24491","doi":"10.1038/s41598-025-09490-1","pmid":"40628864","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10395","title":"Antimicrobial Neuropeptides and Their Receptors: Immunoregulator and Therapeutic Targets for Immune Disorders.","authors":"Chen, Kaiqi; Wu, Xiaojun; Li, Xiaoke; Pan, Haoxuan; Zhang, Wenhui; Shang, Jinxi; Di, Yinuo; Liu, Ruonan; Zheng, Zhaodi; Hou, Xitan","year":2025,"journal":"Molecules (Basel, Switzerland), 30(3)","doi":"10.3390/molecules30030568","pmid":"39942672","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies and characterizes 10 antimicrobial neuropeptides with dual immune functions:\n\n1. PACAP — anti-inflammatory, neuroprotective\n2. VIP — immunosuppressive, anti-inflammatory\n3. α-MSH — anti-inflammatory, antimicrobial\n4. Ghrelin — anti-inflammatory, metabolic regulation\n5. Adrenomedullin — vasodilatory, antimicrobial\n6. NPY — immune cell modulation\n7. Urocortin II — stress response, immunomodulation\n8. CGRP — neurogenic inflammation, vasodilation\n9. Substance P — pro-inflammatory, antimicrobial\n10. Catestatin — antimicrobial, immune modulation\n\nThese neuropeptides share structural similarities with traditional antimicrobial peptides and are directly involved in innate immunity. Their specific receptors represent therapeutic targets for immune-related diseases.","whyItMatters":"The discovery that neuropeptides have antimicrobial properties blurs the traditional boundary between the nervous and immune systems. This has profound implications: it means the brain and nerves are active participants in fighting infections, not just passive bystanders. For drug development, it opens the possibility of targeting neuropeptide receptors to treat autoimmune diseases, chronic inflammation, and infections — using the body's own neuroimmune communication system as a therapeutic lever.","specificNumbers":"","methodology":"Narrative review examining the expression characteristics, antimicrobial activities, and receptor-mediated immunomodulatory mechanisms of 10 neuropeptides. The authors summarize evidence for each peptide's role in innate immunity and catalog potential drugs targeting their receptors for immune-related disorders.","limitations":"As a narrative review, the paper synthesizes existing literature without systematic quality assessment. The antimicrobial activity of some neuropeptides has been demonstrated primarily in vitro and may not translate directly to in vivo efficacy. The therapeutic potential of targeting neuropeptide receptors for immune disorders is largely theoretical, with most drug candidates still in early development. The review covers 10 peptides broadly rather than providing deep mechanistic analysis of each."},{"rthcId":"RPEP-10396","title":"Chirality Interplay of Peptide and Saccharide on Glycopeptide Self-Assembly.","authors":"Chen, Limin; Zhou, Xiao; Huang, Yingying; Wang, Xin; Gao, Xiaoqing; Cao, Yi; Li, Wenfei; Zhou, Yunlong","year":2025,"journal":"Nano letters, 25(4), 1558-1566","doi":"10.1021/acs.nanolett.4c05635","pmid":"39823271","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10397","title":"Risk factors for heart failure within one year after percutaneous coronary intervention in patients with acute coronary syndrome: development of a predictive model.","authors":"Chen, Lin; Xu, Mingzhu; Zhu, Yan; Jiang, Tingbo","year":2025,"journal":"American journal of translational research, 17(11), 8779-8790","doi":"10.62347/DTOE6334","pmid":"41415051","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10398","title":"Trojan Horse-Inspired Biomimetic Lipoprotein Nanocarrier for Noninvasive Anti-VEGF Therapy of Ocular Fundus Neovascularization.","authors":"Chen, Lin; Fan, Chen; Wang, Antian; Zhang, Chenyun; Li, Peiying; Yu, Renhe; Shi, Kexin; Chen, Minghao; Yang, Shiqi; Shi, Wen; Song, Qingxiang; Jiang, Gan; Huang, Yukun; Gao, Xiaoling; Sun, Xiaodong","year":2025,"journal":"Advanced materials (Deerfield Beach, Fla.), 37(44), e08104","doi":"10.1002/adma.202508104","pmid":"40874449","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10399","title":"Vasoactive intestinal peptide reduces ocular hypertension by regulating tight junction of trabecular meshwork through Rab13/PKA signalling complex.","authors":"Chen, Liwen; Yan, Xiaoqin; Luo, Zhaoxia; Cheng, Yang; Li, Mu","year":2025,"journal":"Annals of medicine, 57(1), 2534527","doi":"10.1080/07853890.2025.2534527","pmid":"40859875","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10400","title":"Glucose-dependent insulinotropic polypeptide/glucagon-like peptide 1 receptor agonist tirzepatide promotes branched chain amino acid catabolism to prevent myocardial infarction in non-diabetic mice.","authors":"Chen, Mengya; Zhao, Nan; Shi, Wenke; Xing, Yun; Liu, Shiqiang; Meng, Xianxian; Li, Lanlan; Zhang, Heng; Meng, Yanyan; Xie, Saiyang; Deng, Wei","year":2025,"journal":"Cardiovascular research, 121(3), 454-467","doi":"10.1093/cvr/cvaf005","pmid":"39928435","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10401","title":"Salivary Antimicrobial Peptide in Patients With Dementia Before and After Clinical Oral Rehabilitation Programme: A Randomised Controlled Trial.","authors":"Chen, Ming-An; Yang, Yuan-Han; Liu, Ching-Kuan; Matsuo, Koichiro; Hsu, Chih-Cheng; Lin, Ying-Chu; Huang, Hsiao-Ling","year":2025,"journal":"Journal of oral rehabilitation, 52(1), 1-8","doi":"10.1111/joor.13867","pmid":"39370532","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In this RCT of 55 dementia patients, the experimental group receiving oral rehabilitation showed significantly lower histatin-5 (HTN-5) levels at 3 months (β=-0.08, effect size=0.72), improved salivary flow rate at 6 months (β=0.89, ES=0.89), and better oral health quality of life at 6 months (β=6.99, ES=1.31) compared to controls. Changes in salivary flow rate (β=4.03), HTN-5 level (β=-0.78), and beta-defensin 2 level (β=-0.91) at 3 months all predicted improved quality of life at 6 months (all p<0.05).","whyItMatters":"Dementia patients are at high risk for poor oral health, which is linked to aspiration pneumonia, nutritional decline, and reduced quality of life. This study shows that salivary antimicrobial peptides — histatin-5 and beta-defensin 2 — can serve as measurable biomarkers of oral health improvement, providing objective evidence that oral rehabilitation programs work and offering a new way to monitor oral health in patients who may struggle to report symptoms.","specificNumbers":"","methodology":"This was a randomized controlled trial with 55 dementia patients (28 experimental, 27 control). Both groups received oral health information leaflets. The experimental group additionally received individualized oral muscle exercises and oral self-care practice. Saliva samples and oral health quality of life data were collected at baseline and follow-up. Changes were analyzed using generalized estimating equation models.","limitations":"The sample size of 55 patients is relatively small for an RCT. The study did not assess specific oral pathogens, so the relationship between peptide changes and microbial ecology is unclear. Dementia severity varied, which could influence both oral care compliance and outcomes. The 6-month follow-up may not capture long-term effects."},{"rthcId":"RPEP-10402","title":"Tirzepatide, a dual GLP-1 and GIP receptor agonist, promotes bone loss in obese mice via gut microbial-related metabolites.","authors":"Chen, Ning; Zhang, Mengdan; Shi, Baohong; Luo, Xiumei; Huang, Rui; Luo, Zhengqiong; He, Junliang; Xue, Shengye; Li, Na; Ling, Zemin; Guo, Hao; Xu, Ren; Liu, Yuejun","year":2025,"journal":"Journal of orthopaedic translation, 55, 280-292","doi":"10.1016/j.jot.2025.09.002","pmid":"41089557","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10403","title":"Enhanced Transdermal Delivery of Liraglutide for Sustained Obesity Management.","authors":"Chen, Nipeng; Zeng, Zhipeng; Chen, Haolin; Liu, Hong; Zhang, Zhihui; Ke, Fangfang; Ji, Xiaoyu; Liu, Lixin; Zhang, Zhen; Chen, Yongming","year":2025,"journal":"Langmuir : the ACS journal of surfaces and colloids, 41(19), 12189-12198","doi":"10.1021/acs.langmuir.5c00949","pmid":"40347179","tags":["glp-1-agonists","drug-delivery"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"The researchers built a two-step nanoparticle platform using flash nanocomplexation (FNC) technology. Liraglutide was first encapsulated in nanoparticles formed by tannic acid and aluminum ions held together by coordination and hydrogen bonding. These particles were then coated with positively charged hydroxypropyl trimethylammonium chloride chitosan (HTCC) to boost skin penetration.\n\nThe resulting nanoparticles demonstrated superior transdermal penetration compared to unformulated liraglutide, produced durable blood-sugar-lowering effects, and showed long-acting therapeutic efficacy against obesity in a mouse model.","whyItMatters":"Needle phobia and injection fatigue are real barriers to GLP-1 drug adherence. If liraglutide could be delivered painlessly through the skin, more patients might stick with treatment long-term. This nanoparticle platform could also be adapted for other peptide drugs that currently require injection.","specificNumbers":"Two-step FNC nanoparticle platform; TA-Al3+ coordination with HTCC coating; superior transdermal penetration; sustained hypoglycemic effects in mice","methodology":"This was a laboratory and animal study. The researchers used flash nanocomplexation technology to create nanoparticles encapsulating liraglutide, then tested their ability to penetrate skin barriers and produce therapeutic effects in obese mice. The nanoparticles were characterized for size, charge, and stability, then evaluated for transdermal penetration, blood sugar control, and weight management outcomes.","limitations":"This is an early-stage animal study using mice, so human skin penetration and efficacy are unproven. The abstract does not report specific numbers for weight loss, blood sugar reduction, or skin penetration rates. Long-term safety of the nanoparticle materials applied to skin is unknown. Scaling from laboratory to clinical manufacturing would require significant additional development."},{"rthcId":"RPEP-10404","title":"Exploring Liraglutide's mechanism in reducing renal fibrosis: the Fsp1-CoQ10-NAD(P)H pathway.","authors":"Chen, Qi; Song, Ji-Xian; Zhang, Zhi; An, Ji-Ren; Gou, Yu-Jing; Tan, Miao; Zhao, Yashuo","year":2025,"journal":"Scientific reports, 15(1), 1754","doi":"10.1038/s41598-025-85658-z","pmid":"39799153","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In db/db diabetic mice treated with liraglutide (200 µg/kg/day for 6 weeks), multiple kidney-protective effects were observed:\n\n- Improved renal function and reduced kidney fibrosis\n- Upregulated antioxidant enzymes (T-SOD, GSH-Px, GSH)\n- Reduced oxidative damage markers (8-OHDG, MDA, LPO, 4-HNE, 12-Lox, NOX4)\n- Decreased iron deposition via reduced TfR1 (iron import) and increased FPN1 (iron export)\n- Inhibited ferroptosis through activation of the Fsp1-CoQ10-NAD(P)H pathway\n\nIn vitro experiments confirmed that liraglutide protected cells from high glucose-induced viability decline and lipid peroxidation through the same pathway.","whyItMatters":"Diabetic kidney disease is the leading cause of kidney failure worldwide, and fibrosis is the final common pathway of kidney damage. Identifying that liraglutide protects kidneys by blocking ferroptosis through a specific molecular pathway provides a mechanistic explanation for the clinical kidney benefits already observed in GLP-1 drug trials. This could lead to more targeted therapies and help identify which patients might benefit most from GLP-1 kidney protection.","specificNumbers":"","methodology":"Researchers used db/db mice (a genetic model of type 2 diabetes) and treated them with daily intraperitoneal liraglutide injections (200 µg/kg/day) for 6 weeks. They assessed kidney function, histopathology, lipid peroxidation levels, iron accumulation, and ferroptosis markers. Antioxidant enzyme activities and oxidative stress markers were measured. Iron metabolism was evaluated by examining transferrin receptor 1 (TfR1) and ferroportin 1 (FPN1) expression. The Fsp1-CoQ10-NAD(P)H pathway was investigated both in vivo and in complementary in vitro experiments using high-glucose-treated cells.","limitations":"The study was conducted entirely in mice (db/db model) and cell culture, which may not perfectly replicate human diabetic kidney disease. The db/db mouse is a severe genetic model of obesity-driven diabetes that differs from typical human type 2 diabetes. The 6-week treatment period is relatively short for assessing fibrosis outcomes. Liraglutide was administered intraperitoneally rather than subcutaneously (the human route). The study did not compare against other GLP-1 drugs or include a ferroptosis-specific positive control to confirm pathway specificity."},{"rthcId":"RPEP-10405","title":"An Anionic Cathelicidin Exerts Antimelanoma Effects in Mice by Promoting Pyroptosis.","authors":"Chen, Qian; Feng, Guizhu; Shen, Yan; Li, Xiang; Pei, Qiqi; Wang, Hanying; Tian, Li; Cao, Yuanyuan; Wu, Jing; Yang, Hailong; Mu, Lixian","year":2025,"journal":"Journal of medicinal chemistry, 68(8), 8618-8633","doi":"10.1021/acs.jmedchem.5c00281","pmid":"40207383","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10406","title":"Dose-Response Relationship of Glucagon-like Peptide-1 Receptor Agonists on HbA1c and Body Weight in Type 2 Diabetes Mellitus: A Systematic Review and Network Meta-Analysis.","authors":"Chen, Qian-Qin; Yang, Yong; Xu, Jian-Ya; Wang, Junyu; Fang, Tuan-Yu; Yuan, Yuan; Wang, Chengji; Zhang, Li","year":2025,"journal":"Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists, 31(2), 188-197","doi":"10.1016/j.eprac.2024.11.013","pmid":"39638244","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10407","title":"The 200 most influential publications in migraine research: a bibliometric mapping of the intellectual landscape.","authors":"Chen, Qianxiu; Wei, Shijie; Jiang, Guoliang; Hu, Xiaowei; Zhang, Lili; Li, Pengcheng; Han, Jing","year":2025,"journal":"Frontiers in neurology, 16, 1711571","doi":"10.3389/fneur.2025.1711571","pmid":"41404467","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10408","title":"Osteocyte Neuropeptide Y Aggravates Bone Loss in OVX Mice by Inhibiting Preosteoclast Proliferation and PDGF-BB-Induced Type H Vessel Formation Through PI3K/Akt Signaling Pathway.","authors":"Chen, Qingchang; Zhang, Yan","year":2025,"journal":"Calcified tissue international, 116(1), 134","doi":"10.1007/s00223-025-01443-0","pmid":"41186709","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10409","title":"CPPCGM: A Highly Efficient Sequence-Based Tool for Simultaneously Identifying and Generating Cell-Penetrating Peptides.","authors":"Chen, Qiufen; Zhang, Yuewei; Gao, Jiali; Zhang, Jun","year":2025,"journal":"Journal of chemical information and modeling, 65(7), 3357-3369","doi":"10.1021/acs.jcim.5c00199","pmid":"40105337","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CPPCGM, a deep learning framework using protein language models, achieved state-of-the-art performance in both identifying and generating cell-penetrating peptides. The classifier achieved Matthews correlation coefficient scores of 0.876, 0.923, and 0.664 across three benchmark datasets — significantly outperforming existing methods.\n\nThe generator component (similar to a generative adversarial network) successfully created novel CPP sequences not present in training data, with qualitative and quantitative evaluation confirming their CPP-like properties. The tool is publicly available on GitHub.","whyItMatters":"Discovering new cell-penetrating peptides through laboratory experiments is slow and expensive. This AI tool can rapidly screen and even design novel CPPs from scratch using only sequence information, potentially accelerating the development of peptide-based drug delivery systems. The use of protein language models (PLMs) — similar to how large language models work on text — represents a new frontier in computational peptide design.","specificNumbers":"MCC scores: 0.876, 0.923, 0.664 across 3 datasets · Outperformed state-of-the-art methods · Novel CPPs generated · 3 pretrained models used · Open-source on GitHub","methodology":"The CPPCGM framework has two components: CPPClassifier uses three pretrained protein language models with voting-based classification to distinguish CPPs from non-CPPs. CPPGenerator uses a GAN-like architecture (discriminator + generator) to create novel CPP sequences. Performance was evaluated on three benchmark datasets using Matthews correlation coefficient. Generated peptides were assessed through qualitative analysis and quantitative comparison to known CPP properties.","limitations":"The generated CPPs are computationally predicted and have not been experimentally validated for actual cell-penetrating ability. Classification performance varied across datasets (MCC 0.664 on one dataset suggests limitations in certain contexts). The tool predicts cell-penetrating potential but cannot predict cargo delivery efficiency, toxicity, or in vivo behavior. Experimental synthesis and testing of generated candidates would be needed before therapeutic application."},{"rthcId":"RPEP-10410","title":"Vasostatin-2 attenuates injury-induced neointimal hyperplasia through the ACE2/MasR/PPARγ/NR1D1/Gas1 axis.","authors":"Chen, Qiujing; Liu, Jingmeng; Madonna, Rosalinda; Li, Feifei; Chen, Shuai; Li, Leying; Wu, Xinrui; Maimati, Yipaerguli; Ding, Fenghua; Wang, Xiaoqun; Shen, Ying; Zhang, Ruiyan; Shen, Weifeng; Dai, Yang; Lu, Lin; De Caterina, Raffaele","year":2025,"journal":"Cardiovascular research, 121(14), 2260-2277","doi":"10.1093/cvr/cvaf192","pmid":"41231769","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Vasostatin-2, a bioactive peptide cleaved from chromogranin A, prevents artery re-narrowing after coronary stent placement. Patients with coronary restenosis had significantly lower serum vasostatin-2 levels than those without (p<0.001). In mice, recombinant vasostatin-2 inhibited neointimal hyperplasia after arterial injury by binding to ACE2, activating the NR1D1/Gas1 pathway, promoting smooth muscle cell death, and preventing their excessive proliferation. Mutant vasostatin-2 that couldn't bind ACE2 lost its protective effect.","whyItMatters":"Coronary stent restenosis (re-narrowing of arteries after treatment) remains a significant clinical problem affecting up to 10% of patients after coronary angioplasty. Vasostatin-2 is a naturally occurring peptide biomarker that predicts restenosis risk and may itself be therapeutic. This study identifies both a predictive biomarker and a potential treatment target for one of cardiology's persistent challenges.","specificNumbers":"n=884 patients (442 with restenosis, 442 without) · lower vasostatin-2 in restenosis group (p<0.001) · inhibited neointimal hyperplasia in mice · ACE2/MasR/PPARγ/NR1D1/Gas1 pathway identified · multi-omics validation","methodology":"The study combined clinical and preclinical approaches. Clinically, serum vasostatin-2 levels were measured in 884 patients with and without restenosis after PCI. Preclinically, recombinant vasostatin-2 or saline was administered in a mouse femoral artery injury model. Multi-omics approaches (bulk RNA sequencing, CUT&Tag, GST pull-down/mass spectrometry) characterized the mechanism. ACE2-binding incompetent vasostatin-2 mutants and NR1D1-deficient VSMCs validated the pathway.","limitations":"The clinical portion is observational (association, not causation). The preclinical model used femoral artery injury in mice, which differs from human coronary stent restenosis. Whether exogenous vasostatin-2 administration could prevent restenosis in humans has not been tested. The optimal dosing, route, and timing of vasostatin-2 delivery for potential therapeutic use were not established."},{"rthcId":"RPEP-10411","title":"Effects of an antimicrobial peptide on transport- and novel environment-induced stress in British Shorthair cats.","authors":"Chen, Shaohao; Zhang, Miaomiao; Yan, Haoran; Ye, Lan; Xue, Qishan; Wu, Yuansheng; Zhao, Kun; Jiang, Yizhou; Wang, Qingxin; Zhu, Jiang; Guo, Yan; Liu, Qingshen; Deng, Baichuan; Zhang, Lingna","year":2025,"journal":"Frontiers in veterinary science, 12, 1724637","doi":"10.3389/fvets.2025.1724637","pmid":"41726387","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10412","title":"An effective approach to obtain functional poly-β-peptides for combating drug-resistant bacterial infections.","authors":"Chen, Sheng; Luo, Zhengjie; Zhou, Min; Xiao, Ximian; Cong, Zihao; Xie, Jiayang; Wu, Yueming; Zhang, Haodong; Zhao, Xuebin; Song, Gonghua; Liu, Runhui","year":2025,"journal":"Journal of materials chemistry. B, 13(18), 5315-5326","doi":"10.1039/d5tb00184f","pmid":"40227873","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10413","title":"Host Defense Peptide-Mimicking Poly(2-oxazoline)s Displaying Potent Activities toward Phytopathogens to Alleviate Antimicrobial Resistance in Agriculture.","authors":"Chen, Sheng; Zhou, Min; Xiao, Ximian; Xie, Jiayang; Liu, Longqiang; Cong, Zihao; Zhao, Xuebin; Hu, Weilong; Wang, Jie; Song, Gonghua; Liu, Runhui","year":2025,"journal":"Journal of agricultural and food chemistry, 73(14), 8191-8203","doi":"10.1021/acs.jafc.4c12430","pmid":"40138468","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10414","title":"Bacteria biohybrids integrating anticancer peptide-loaded nanoparticles for tumor immunotherapy through pyroptosis activation.","authors":"Chen, Shiyi; Ouyang, Xunping; Wei, Xue; He, Gang; Xian, Yiwen; Zhang, Chong; Wu, Decheng","year":2025,"journal":"Biomaterials science, 13(22), 6423-6432","doi":"10.1039/d5bm00667h","pmid":"41054933","tags":[],"studyType":"animal","evidenceStrength":"early","keyFinding":"A bacteria-based biohybrid system (P/L@EcN) combining the probiotic E. coli Nissle 1917 with nanoparticles loaded with the anticancer peptide ruxotemitide (LTX-315) successfully suppressed tumor growth in a mouse breast cancer model. The system achieved enhanced tumor accumulation and penetration, triggered cancer cell death through pyroptosis (caspase-1-dependent), remodeled the tumor immune environment by boosting M1 macrophages and reducing immune-suppressive MDSCs, and showed no systemic toxicity.","whyItMatters":"This study demonstrates a creative approach to cancer immunotherapy: using bacteria as living delivery vehicles for anticancer peptides. By combining bacterial tumor-targeting ability with a peptide that triggers inflammatory cancer cell death (pyroptosis), the system activates the immune system against tumors in a way that neither component could achieve alone.","specificNumbers":"Peptide: ruxotemitide (LTX-315) · Bacteria: E. coli Nissle 1917 · Improved M1/M2 macrophage ratio · Reduced MDSCs · No systemic toxicity","methodology":"Researchers created a biohybrid by conjugating ROS-responsive, peptide-loaded PEG-PLGA nanoparticles to tumor-targeting probiotic E. coli Nissle 1917 using copper-free click chemistry. The system was tested for tumor accumulation, cellular uptake, tumor penetration, and pyroptosis induction in vitro, then evaluated in an orthotopic breast cancer mouse model for anti-tumor efficacy and immune remodeling.","limitations":"Mouse study with a single tumor type (orthotopic breast cancer). Long-term safety of introducing engineered bacteria into patients is unknown. Clinical translation of bacteria-based delivery systems faces major regulatory hurdles. Specific quantitative results (tumor size reduction percentages, survival data) not detailed in abstract."},{"rthcId":"RPEP-10415","title":"Prognostic benefit of glucagon-like peptide-1 receptor agonists addition to sodium-glucose cotransporter 2 inhibitors in patients with atherosclerotic cardiovascular disease and heart failure: a cohort study.","authors":"Chen, Sih-Yao; Wu, Jheng-Yan; Liao, Kuang-Ming; Lin, Yu-Min","year":2025,"journal":"European heart journal. Cardiovascular pharmacotherapy, 11(4), 324-333","doi":"10.1093/ehjcvp/pvaf014","pmid":"39963713","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10416","title":"Effects of Glucagon-Like Peptide-1 Receptor Agonist on Facial Landmarks.","authors":"Chen, Teresa H; Li, Joy; Hellbusch, Dylan; Tao, Jeremiah P","year":2025,"journal":"Ophthalmic plastic and reconstructive surgery","doi":"10.1097/IOP.0000000000003070","pmid":"41022041","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10417","title":"GLP-1 RAs and Cardiovascular and Kidney Outcomes by Body Mass Index in Type 2 Diabetes.","authors":"Chen, Tien-Hsing; Hu, En-Hao; Chen, Dong-Yi; Lin, Yuan; Chou, Tien-Shin; Lin, Ming-Shyan; Yang, Ning-I; Wang, Chao-Yung; Hung, Ming-Jui; Tsai, Ming-Lung","year":2025,"journal":"JAMA network open, 8(9), e2530952","doi":"10.1001/jamanetworkopen.2025.30952","pmid":"40920377","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10418","title":"GLP-1 receptor agonists and risk of hepatocellular carcinoma and all-cause mortality in patients with MASLD and type 2 diabetes: a propensity score-matched population-based cohort study.","authors":"Chen, Wan-Ming; Ng, Hui-Ji; Jao, An-Tzu; Wu, Szu-Yuan; Soong, Ruey-Shyang","year":2025,"journal":"Diabetes research and clinical practice, 227, 112407","doi":"10.1016/j.diabres.2025.112407","pmid":"40803507","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10419","title":"Meta-analysis of the effects of semaglutide on body mass index (BMI) and blood lipid levels in polycystic ovary syndrome patients.","authors":"Chen, Wansu; Xu, Dan; Shao, Xueting; Song, Qingxia; Chen, Renshou","year":2025,"journal":"Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology, 41(1), 2553052","doi":"10.1080/09513590.2025.2553052","pmid":"40960939","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10420","title":"Dual-pathological cascade delivery of apoptotic vesicles for targeted therapy in intervertebral disc degeneration.","authors":"Chen, Wei; Zhao, Tianyuan; Ren, Yiming; Huang, Wenzhe; Xia, Jiyuan; Hu, Zhenxin; Chen, Libo; Li, Hao; Zhang, Qi; Wang, Han; Cui, Penglei; Guo, Quanyi; He, Da","year":2025,"journal":"Materials today. Bio, 34, 102200","doi":"10.1016/j.mtbio.2025.102200","pmid":"40893365","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10421","title":"Glucagon-like peptide-1 receptor agonists and sarcopenia-related markers in diabetes: A systematic review and meta-analysis.","authors":"Chen, Wenjie; Qin, Hongzhuo; Zhou, Zhaokai; Chen, Yun; Xu, Xiaowei; Chen, Yajun; He, Jieyu; Xu, Ran; Gao, Hua; Lu, Qiong","year":2025,"journal":"Clinical nutrition (Edinburgh, Scotland), 55, 42-56","doi":"10.1016/j.clnu.2025.10.006","pmid":"41187492","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10422","title":"Investigating the Microbiota-Gut-Brain Axis Mechanisms of Transcutaneous Auricular Vagus Nerve Stimulation in Patients with Obesity: A Study Protocol for a Randomized Controlled Trial.","authors":"Chen, Xia; Kong, Weiqing; Song, Yang; Huang, Wei; Zhang, Yanji; Liu, Zhi; Zhou, Zhongyu; Fu, Chengwei","year":2025,"journal":"Diabetes, metabolic syndrome and obesity : targets and therapy, 18, 3895-3904","doi":"10.2147/DMSO.S558226","pmid":"41141981","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10423","title":"Design, characterization, and application of novel antimicrobial peptides against Bacillus cereus.","authors":"Chen, Xiaowei; Cai, Yi; Huang, Shanyu; Pu, Donglin; Xu, Zhenbo; Soteyome, Thanapop; Zhu, Jun; Ye, Yanrui; Lin, Xiaomei","year":2025,"journal":"International journal of food microbiology, 442, 111398","doi":"10.1016/j.ijfoodmicro.2025.111398","pmid":"40845568","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10424","title":"Delayed Cardiac Dysfunction During Prolonged Use of Trastuzumab for the Treatment of HER2-Positive Metastatic Breast Cancer.","authors":"Chen, Xuelian; Lan, Xiaofeng; Xiao, Li; Song, Lin; Huang, Jiayi; Xie, Xiaofeng; Chen, Liping; Bai, Xue; Du, Caiwen","year":2025,"journal":"Breast cancer (Dove Medical Press), 17, 1101-1110","doi":"10.2147/BCTT.S553442","pmid":"41328430","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10425","title":"Liraglutide suppresses ferroptosis by upregulation NRF2 in type 2 diabetic cardiomyopathy.","authors":"Chen, Xuepin; Wang, Tianying; Gao, Yan; Wang, Guo An; Guan, Jun; Dai, Hongyan","year":2025,"journal":"Peptides, 192, 171429","doi":"10.1016/j.peptides.2025.171429","pmid":"40680859","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Liraglutide (200 μg/kg/day for 8 weeks) improved glucose metabolism, cardiac remodeling, and heart function while reducing lipid peroxidation and ferroptosis in Goto-Kakizaki diabetic rats. The drug upregulated ferroptosis-related protective proteins including NRF2 (both cytoplasmic and nuclear forms), GPX4, and FTH-1.\n\nIn cell culture, high glucose triggered lipid reactive oxygen species production, reduced mitochondrial mass, and lowered ferroptosis-protective proteins — effects that were reversed by liraglutide treatment. Silencing NRF2 with siRNA abolished liraglutide's protective effects, confirming NRF2 as the key mediator of its anti-ferroptotic action.","whyItMatters":"Ferroptosis is increasingly recognized as a driver of organ damage in diabetes, but targeted treatments are lacking. This study suggests that liraglutide — already FDA-approved and widely prescribed for diabetes — may provide heart protection through an entirely new mechanism beyond blood sugar control, potentially expanding the rationale for its use in diabetic patients at risk of heart disease.","specificNumbers":"","methodology":"The in vivo model used Goto-Kakizaki (GK) rats, a spontaneous type 2 diabetes strain, treated with subcutaneous liraglutide at 200 μg/kg/day for 8 weeks. Cardiac function, glucose metabolism, lipid peroxidation markers, and ferroptosis-related protein levels were assessed. In vitro experiments used H9C2 rat heart cells exposed to high glucose with or without liraglutide, NRF2 siRNA knockdown, and the ferroptosis inhibitor ferrostatin-1 (Fer-1).","limitations":"This was an animal and cell culture study — the findings have not been confirmed in human patients with diabetic cardiomyopathy. The Goto-Kakizaki rat model does not perfectly replicate human type 2 diabetes. Specific quantitative outcomes (effect sizes, statistical values) for cardiac function improvements were not detailed in the abstract. The 8-week treatment duration may not reflect long-term effects."},{"rthcId":"RPEP-10426","title":"The Effect of Semaglutide on Gut Microbiota in Chinese Patients with Type 2 Diabetes Poorly Controlled by Metformin.","authors":"Chen, Yanxia; Shan, Yue; Wang, Ting; Liu, Zhihong; Zhao, Zhansheng; He, Yinxi","year":2025,"journal":"Diabetes, metabolic syndrome and obesity : targets and therapy, 18, 3865-3881","doi":"10.2147/DMSO.S537001","pmid":"41132642","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10427","title":"Peptidylglycine alpha-amidating monooxygenase is important in mice for beta-cell cilia formation and insulin secretion but promotes diabetes risk through beta-cell independent mechanisms.","authors":"Chen, Yi-Chun; Bäck, Nils E; Zhen, Jenicia; Xiong, Lena; Komba, Mitsuhiro; Gloyn, Anna L; MacDonald, Patrick E; Mains, Richard E; Eipper, Betty A; Verchere, C Bruce","year":2025,"journal":"Molecular metabolism, 96, 102123","doi":"10.1016/j.molmet.2025.102123","pmid":"40120979","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10428","title":"Immune checkpoint inhibitor-associated diabetes mellitus: mechanisms, clinical manifestations, and management strategies.","authors":"Chen, Yu; Wang, Xiaolu; Duan, Shuyun","year":2025,"journal":"Frontiers in endocrinology, 16, 1679751","doi":"10.3389/fendo.2025.1679751","pmid":"41607457","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10429","title":"Novel oncolytic adenovirus-based PEPvIII vaccine displays a super antitumor effect in glioma models.","authors":"Chen, Yuankun; Ren, Lingyue; Li, Xia; Wu, Yufan; Zhao, Hongjuan; Feng, Ruru; Zhang, Weifeng; Zhao, Junli; Yang, Peiyan; Mao, Qinwen; Xia, Haibin","year":2025,"journal":"Journal for immunotherapy of cancer, 13(9)","doi":"10.1136/jitc-2024-010750","pmid":"40998516","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10430","title":"Synergistic effects of NO/H2S gases on antibacterial, anti-inflammatory, and analgesic properties in oral ulcers using a gas-releasing nanoplatform.","authors":"Chen, Yuanqi; Lei, Kezheng; Li, Yinxi; Mu, Zhixiang; Chu, Tengda; Hu, Jiajun; Zeng, Bairui; Wang, Yi; Shen, Jianliang; Cai, Xiaojun; Shi, Tianpeng; Deng, Hui","year":2025,"journal":"Acta biomaterialia, 194, 288-304","doi":"10.1016/j.actbio.2025.01.013","pmid":"39798637","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10431","title":"Exendin-4 improves cerebral ischemia by relaxing microvessels, rapidly increasing cerebral blood flow after reperfusion.","authors":"Chen, Yujie; Wang, Lei; Zhou, Yutong; Wang, Yuguang; Qin, Wei; Wang, Mingxiao; Liu, Bo; Tian, Qian; Xu, Huisen; Shen, Hui; Zheng, Chen","year":2025,"journal":"Basic research in cardiology, 120(2), 423-441","doi":"10.1007/s00395-025-01096-y","pmid":"40121575","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10432","title":"Construction and validation of a prediction model for early recurrence after catheter ablation in patients with persistent atrial fibrillation based on BNP, Ang Ⅱ, homocysteine, MHR, NLR.","authors":"Chen, Yuning; Sun, Guojian; Zhu, Zhijun; Shen, Farong","year":2025,"journal":"Frontiers in cardiovascular medicine, 12, 1589351","doi":"10.3389/fcvm.2025.1589351","pmid":"40454234","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10433","title":"Signatures of proteomics and glycoproteomics revealed liraglutide ameliorates MASLD by regulating specific metabolic homeostasis in mice.","authors":"Chen, Yuxuan; Liu, Chendong; Yang, Qian; Yang, Jingtao; Zhang, He; Zhang, Yong; Feng, Yanruyu; Liu, Jiaqi; Li, Lian; Li, Dapeng","year":2025,"journal":"Journal of pharmaceutical analysis, 15(11), 101273","doi":"10.1016/j.jpha.2025.101273","pmid":"41377138","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10434","title":"Structure- or size-transformable peptide-based antibacterial biomaterials: Design strategies, functions, and applications.","authors":"Chen, Zhenduo; Zhao, Guanghui; Qu, Yuankai; Tang, Qi; Yang, Shuaikang; Zhou, Chenlong; Li, Mingtan; Kang, Yunlu; Tan, Peng; Ma, Xi","year":2025,"journal":"Acta biomaterialia, 208, 119-145","doi":"10.1016/j.actbio.2025.10.035","pmid":"41130431","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10435","title":"Effect of glucagon-like peptide-1 receptor agonists in osteoarthritis: A systematic review of pre-clinical and human studies.","authors":"Cheng, Jacinta; Solomon, Tia; Estee, Mahnuma; Cicuttini, Flavia M; Lim, Yuan Z","year":2025,"journal":"Osteoarthritis and cartilage open, 7(1), 100567","doi":"10.1016/j.ocarto.2025.100567","pmid":"39995585","tags":[],"studyType":"systematic-review","evidenceStrength":"low","keyFinding":"This systematic review of 11 studies (7 preclinical, 4 human) found consistent signals that GLP-1 receptor agonists may protect cartilage, reduce inflammation, and relieve pain in osteoarthritis. Preclinical studies showed favorable chondroprotective and immunomodulatory effects with a dose-dependent response, primarily through inhibition of the NF-κB inflammatory pathway. The limited human studies supported these findings.\n\nGLP-1 agonists were assessed for structural effects (cartilage protection), immunomodulation, analgesia, and molecular pathway effects in osteoarthritis. The evidence, while limited, was consistently positive across both animal and human studies.","whyItMatters":"Osteoarthritis affects hundreds of millions of people worldwide and has no disease-modifying treatment. With millions already taking GLP-1 drugs for weight loss and diabetes, discovering that these same drugs may directly protect joints — beyond just reducing weight-related joint stress — could be transformative. The NF-κB inhibition mechanism suggests genuine anti-inflammatory action in joints, not just a secondary benefit of weight loss.","specificNumbers":"11 studies total · 7 preclinical · 4 human · structural effects (n=6 preclinical, n=1 human) · immunomodulation (n=7) · analgesia (n=1) · dose-dependent effect · NF-κB pathway inhibition","methodology":"Systematic review searching Ovid Medline, Embase, and CINAHL from inception through November 2024. Three independent reviewers conducted risk of bias assessment and data extraction. Qualitative evidence synthesis was performed. Prospectively registered on PROSPERO (two registrations). Included studies examining GLP-1 receptor agonists and osteoarthritis outcomes in both preclinical and human settings.","limitations":"Only 11 studies met inclusion criteria, with just 4 in humans. The evidence base is too small for meta-analysis. Human studies were limited in design quality and sample size. Weight loss from GLP-1 drugs confounds the ability to determine whether joint benefits are direct or mediated through reduced mechanical load. High-quality randomized controlled trials are needed."},{"rthcId":"RPEP-10436","title":"Associations between serum neuropeptide Y levels and anxiety, depression, and quality of life in Chinese patients with primary glaucoma.","authors":"Cheng, Kaihui; Quan, Fu; Dai, Li; Gu, Chao; Yu, Ling","year":2025,"journal":"BMC ophthalmology, 25(1), 448","doi":"10.1186/s12886-025-04286-3","pmid":"40775618","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10437","title":"Scorpion Venom Heat-Resistant Synthetic Peptide Alleviates DSS-Induced Colitis via α7nAChR-Mediated Modulation of the JAK2/STAT3 Pathway.","authors":"Cheng, Kang; He, Guangbo; Li, Xiaxia; Li, Yuqian; Cui, Xiaolin; Wu, Xuefei; Hong, Jau-Shyong; Zhao, Jie; Li, Sheng; Guo, Yanjie","year":2025,"journal":"Antioxidants (Basel, Switzerland), 14(11)","doi":"10.3390/antiox14111296","pmid":"41300453","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10438","title":"RBC Membrane-Camouflaged Nanosystem-Mediated Synergistic Drug Combination for Enhanced Anti-Tumor Therapy.","authors":"Cheng, Qian; Zhong, Xuemei; Deng, Lu; He, Xinling; Luo, Miaoxizi; Wang, Ruibing; Zhang, Jinming","year":2025,"journal":"Advanced healthcare materials, 14(26), e2500446","doi":"10.1002/adhm.202500446","pmid":"40331462","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10439","title":"Efficacy and safety of catheter ablation with vein of Marshall ethanol infusion in patients with persistent AF and HFrEF.","authors":"Cheng, Shilin; Yin, Jie; Li, Xinran; Wang, Yu; Hu, Hesheng","year":2025,"journal":"Biomedical reports, 23(3), 153","doi":"10.3892/br.2025.2031","pmid":"40746491","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10440","title":"G(1-5)-EM2, a multi-targeted agonist to opioid and growth hormone secretagogue receptors exhibited nontolerance forming antinociceptive effects in a mouse model of burn pain.","authors":"Cheng, Songxia; Ding, Jiali; Xu, Biao; Wang, Yan; Shen, Xiaoyu; Xia, Yanhua; Wu, Lei; Wei, Jie","year":2025,"journal":"European journal of pharmacology, 986, 177148","doi":"10.1016/j.ejphar.2024.177148","pmid":"39586394","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10441","title":"Short-Term Semaglutide Improves Safety in High Body Weight Recipients Undergoing Living Donor Liver Transplant: A Case Report.","authors":"Cheng, Ssu-Min; Lai, Yin; Huang, Ruo-Yi; Lee, Wei-Chen; Lee, Chen-Fang; Wu, Ting-Jung","year":2025,"journal":"Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation, 23(12), 838-841","doi":"10.6002/ect.2025.0244","pmid":"41578754","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10442","title":"Natural Human Antimicrobial Peptides and Female Reproductive Tract Infections.","authors":"Cheng, Tong; Wu, Luming; Tao, Jijun; Tu, Shiyan; Fan, Xue; Wang, Yixiang; Wang, Yiqing","year":2025,"journal":"Archiv der Pharmazie, 358(5), e70008","doi":"10.1002/ardp.70008","pmid":"40376728","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10443","title":"SGLT2 inhibitors for primary prevention of macrovascular and major microvascular complications in type 2 diabetes: an island-wide cohort study.","authors":"Cheng, Wan-Yin; Yen, Fu-Shun; Hung, Yao-Min; Wei, James Cheng-Chung; Lin, Heng-Jun; Huang, Yu-Han; Hsu, Chih-Cheng; Hwu, Chii-Min","year":2025,"journal":"Journal of the Royal Society of Medicine, 118(11), 347-357","doi":"10.1177/01410768251375906","pmid":"41182046","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10444","title":"Case Report: Efficacy and safety of dose-escalated Mazdutide, a GLP-1/GCGR dual agonist, in an adolescent with obesity, type 2 diabetes, and hyperuricemia.","authors":"Cheng, Wenfei; Chen, Zilong; Li, Puyu; Zhang, Yingyu; Ma, Yujin; Liu, Peng; Jiang, Hongwei","year":2025,"journal":"Frontiers in endocrinology, 16, 1654506","doi":"10.3389/fendo.2025.1654506","pmid":"41030857","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Over 36 weeks of dose-escalated Mazdutide (2 mg → 4 mg → 6 mg weekly subcutaneous injections) combined with metformin and insulin, this 15-year-old patient achieved: 16.8 kg weight loss (18.89% BMI reduction from 30.64 kg/m²), HbA1c reduction of 21.88% (from 9.60%), uric acid decrease of 37.00% (from 511 μmol/L), triglyceride reduction of 69.02%, total cholesterol decrease of 13.65%, LDL cholesterol decrease of 17.27%, and complete resolution of hepatic steatosis by week 14. No hypoglycemic episodes or adverse events occurred, and benefits were sustained after treatment.","whyItMatters":"Mazdutide is a next-generation dual-agonist peptide that targets both GLP-1 and glucagon receptors, potentially offering broader metabolic benefits than GLP-1-only drugs like semaglutide. This is one of the first reports of its use in an adolescent, and the comprehensive metabolic improvements — weight loss, blood sugar control, uric acid reduction, lipid improvement, and fatty liver reversal — suggest it could be particularly valuable for young patients with complex metabolic syndrome.","specificNumbers":"","methodology":"This is a single-patient case report. A 15-year-old male with BMI of 30.64 kg/m², HbA1c of 9.60%, and serum uric acid of 511 μmol/L received Mazdutide via subcutaneous injection once weekly, escalating from 2 mg to 4 mg to 6 mg, alongside metformin and insulin. Outcomes were tracked over 36 weeks with blood tests and liver ultrasound imaging.","limitations":"This is a single case report, which cannot establish causality or generalizability. The patient received Mazdutide alongside metformin and insulin, making it impossible to isolate Mazdutide's individual contribution. No control group or comparison arm exists. Long-term safety in adolescents remains unknown. One patient's experience cannot predict population-level outcomes."},{"rthcId":"RPEP-10445","title":"Semaglutide attenuates diabetic retinopathy progression via ameliorating retinal vasculopathy and oxidative stress in vivo and in vitro.","authors":"Cheng, Xiao; Fu, Zhuoxin; Chen, Yucai; Wang, Jiawei; Han, Furong","year":2025,"journal":"Diabetes, obesity & metabolism, 27(12), 7085-7096","doi":"10.1111/dom.70107","pmid":"40931416","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10446","title":"Glucagon-like peptide-1 receptor agonists linked to a reduced risk of developing asthma among patients with type 2 diabetes.","authors":"Cheng, Yung-Sheng; Chung, Chi-Hsiang; Kuo, Shih-Ming; Lin, Chih-Ping; Weng, Tsu-Hsuan; Su, Sheng-Chiang; Lu, Chieh-Hua; Kuo, Feng-Chih; Chien, Wu-Chien; Liang, Yao-Jen; Li, Peng-Fei","year":2025,"journal":"Therapeutic advances in endocrinology and metabolism, 16, 20420188251400536","doi":"10.1177/20420188251400536","pmid":"41425689","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10447","title":"GLP-1 receptor agonist properties of a chimeric peptide derived by hybridization of Latrodectus αLatrotoxin and Heloderma Exendin-4.","authors":"Chepurny, Oleg G; Liles, Amber N; Cham, Nancy; Matsoukas, Minos-Timotheos; Liapakis, George; Meng, Qinghe; Cooney, Robert N; Doyle, Robert P; Holz, George G","year":2025,"journal":"General and comparative endocrinology, 368, 114745","doi":"10.1016/j.ygcen.2025.114745","pmid":"40347985","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10448","title":"Prognostic value of NT-proBNP monitoring in patients with left ventricular assist devices.","authors":"Cherbi, Miloud; Verdaguer, Joaquim; Itier, Romain; Barde, Laurence; Fournier, Pauline; Grunenwald, Etienne; Gaudard, Philippe; Rouvière, Philippe; Molina, Adrien; Ughetto, Aurore; Delmas, Clément","year":2025,"journal":"JHLT open, 10, 100387","doi":"10.1016/j.jhlto.2025.100387","pmid":"41127408","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10449","title":"The Effect of Myrtacine and Celastrol-Enriched Extract on Cutibacterium acnes Extracellular Vesicles.","authors":"Cheung, Caroline T; Mias, Céline; Lancien, Ugo; Corvec, Stéphane; Mengeaud, Valérie; Khammari, Amir; Duplan, Hélène; Dréno, Brigitte","year":2025,"journal":"International journal of dermatology","doi":"10.1111/ijd.70188","pmid":"41403042","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10450","title":"Unmasking Aspiration Risks: A Propensity-Matched Odyssey of GLP-1 Receptor Agonists and Colonoscopy.","authors":"Chhabra, Puneet; Bhandari, Ritesh; Singh, Rituraj","year":2025,"journal":"Journal of gastroenterology and hepatology, 40(11), 2732-2737","doi":"10.1111/jgh.70071","pmid":"40954421","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10451","title":"SHR7280, an oral gonadotropin-releasing hormone antagonist, for the prevention of premature luteinizing hormone surge in controlled ovarian hyperstimulation: a dose-finding, phase 2 trial.","authors":"Chi, Hongbin; Song, Ying; Jin, Lei; Song, Xueru; Wang, Xiaohong; Ma, Qianhong; Cao, Yunxia; Liang, Xiaoyan; Tan, Jichun; Guan, Yichun; Diao, Feiyang; Li, Yanping; Li, Zeli; Sun, Yuqi; Shu, Chang; Chen, Hong; Shen, Kai; Qiao, Jie","year":2025,"journal":"Human reproduction (Oxford, England), 40(7), 1357-1365","doi":"10.1093/humrep/deaf082","pmid":"40373184","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10452","title":"Combating the post-antibiotic era crisis: antimicrobial peptide/peptidomimetic-integrated combination therapies and delivery systems.","authors":"Chi, Jiaying; Lin, Qiaoni; Jin, Bingrui; Ou, Jiayu; Jiang, Ling; Yang, Xinyu; Guo, Jialiang; Peng, Tingting; Lu, Chao","year":2025,"journal":"Journal of materials chemistry. B, 13(38), 11996-12019","doi":"10.1039/d5tb01424g","pmid":"40926726","tags":["antimicrobial-peptides","antibiotic-resistance"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Antimicrobial peptides (AMPs) and peptidomimetics can be combined with conventional antibiotics, quorum sensing inhibitors, metal nanoparticles, and photoresponsive materials to create synergistic therapies that overcome antibiotic resistance. AMPs work primarily by disrupting bacterial cell membranes — a mechanism fundamentally different from conventional antibiotics — which gives them broad-spectrum activity and lower risk of resistance development.\n\nAdvanced delivery systems including nanoparticles, hydrogels, microneedle patches, and inhaled formulations can enhance AMP targeting, prolong therapeutic duration, and reduce systemic toxicity. The review argues that combining AMPs with other antimicrobial agents through smart delivery platforms represents the most promising strategy for addressing the global antibiotic resistance crisis.","whyItMatters":"Antibiotic resistance kills over 1.2 million people annually and new antibiotic development has nearly stalled. AMPs attack bacteria through mechanisms that are much harder to develop resistance against, but they struggle with stability, toxicity, and delivery when used alone. Combining them with conventional drugs and modern delivery systems could create therapies that are both more effective and harder for bacteria to resist — potentially our best weapon in the post-antibiotic era.","specificNumbers":"Delivery systems: nanoparticles + hydrogels + microneedle patches + inhaled formulations · Combinations: antibiotics + quorum sensing inhibitors + metal nanoparticles + photoresponsive materials","methodology":"Comprehensive review covering AMP structure-dependent antimicrobial mechanisms, synergistic combination therapy strategies, and drug delivery system technologies, with case studies from recent literature.","limitations":"As a review, this synthesizes existing research rather than generating new data. Most AMP combination therapies and advanced delivery systems are in preclinical stages. The gap between promising lab results and approved clinical therapies remains wide, with challenges including manufacturing scalability, regulatory pathways for combination products, and cost of complex delivery systems."},{"rthcId":"RPEP-10453","title":"NOX2-mediated reactive oxygen species contribute to angiotensin II-induced cardiac hypertrophy by promoting cardiomyocyte autophagy via Atg4B S-glutathionylation modification.","authors":"Chi, Ruifang; Shi, Fang; He, Juan; Cai, Yan; Lv, Mengzhu; Cao, Huili; Chai, Chanjuan; Zhao, Yanfang; Yang, Bing; Cui, Xuelin","year":2025,"journal":"International immunopharmacology, 162, 115163","doi":"10.1016/j.intimp.2025.115163","pmid":"40618504","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10454","title":"Incretin-based therapy: An update focusing on the major revolution in cardiovascular-kidney-metabolic health.","authors":"Chiang, Chern-En; Wang, Kang-Ling; Cheng, Hao-Min; Chao, Tze-Fan; Sung, Shih-Hsien","year":2025,"journal":"Journal of the Chinese Medical Association : JCMA, 88(8), 585-593","doi":"10.1097/JCMA.0000000000001263","pmid":"40605133","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10455","title":"Glucagon-like peptide 1 receptor agonists and risk of venous thromboembolism: a systematic review and meta-analysis of randomized controlled trials.","authors":"Chiang, Cho-Han; Chang, Yu-Cheng; Yu, Chun-Chiao; See, Xin Ya; Wang, Tsu Hsien; Xanthavanij, Nutchapon; Song, Junmin; Lo, Shao-Wei; Chiang, Cho-Hung; Lake, Leslie; Lauw, Mandy N; Bauer, Kenneth A; Kazi, Dhruv S; Patell, Rushad","year":2025,"journal":"Journal of thrombosis and haemostasis : JTH, 23(11), 3527-3539","doi":"10.1016/j.jtha.2025.06.020","pmid":"40602613","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10456","title":"Glucagon-like Peptide-1 Agonists Reduce Cardiovascular Events in Cancer Patients on Immune Checkpoint Inhibitors.","authors":"Chiang, Cho-Han; Song, Junmin; Chi, Kuan-Yu; Chang, Yu-Cheng; Xanthavanij, Nutchapon; Chang, Yu; Hsia, Yuan Ping; Chiang, Cho-Hung; Ghamari, Azin; Reynolds, Kerry L; Lin, Shuwen; Xu, Xiaocao Haze; Neilan, Tomas G","year":2025,"journal":"European journal of cancer (Oxford, England : 1990), 216, 115170","doi":"10.1016/j.ejca.2024.115170","pmid":"39709670","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10457","title":"Glucagon-Like Peptide-1 Receptor Agonists and Gastrointestinal Adverse Events: A Systematic Review and Meta-Analysis.","authors":"Chiang, Cho-Hung; Jaroenlapnopparat, Aunchalee; Colak, Sena Cakir; Yu, Chun-Chiao; Xanthavanij, Nutchapon; Wang, Tsu-Hsien; See, Xin Ya; Lo, Shao-Wei; Ko, Albert; Chang, Yu-Cheng; Song, Junmin; Hsia, Yuan Ping; Chiang, Cho-Han","year":2025,"journal":"Gastroenterology, 169(6), 1268-1281","doi":"10.1053/j.gastro.2025.06.003","pmid":"40499738","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10458","title":"Proteogenomic approach to immunopeptidomics of ovarian tumors identifies shared peptide vaccine candidates.","authors":"Chiaro, Jacopo; Peltonen, Karita; Õunap, Kadri; Bailey, Aubrey; Feola, Sara; Wojciechowski, Sara; Es-Haghi, Masoumeh; Azkargorta, Mikel; Elortza, Félix; Russo, Salvatore; Sallinen, Hanna; Anttila, Maarit; Gurvich, Olga; Cerullo, Vincenzo; Kekarainen, Tuija","year":2025,"journal":"NPJ vaccines, 10(1), 195","doi":"10.1038/s41541-025-01234-6","pmid":"40819132","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10459","title":"A Pharmacometric Method for Quantitative Determination of Improvement in Body Composition and Characterization of the Exposure-Response Relationship during Treatment of Obesity with Tirzepatide.","authors":"Chigutsa, Emmanuel; Her, Lucy; Ma, Xiaosu; Urva, Shweta; Schneck, Karen","year":2025,"journal":"Clinical pharmacology and therapeutics, 118(6), 1489-1498","doi":"10.1002/cpt.3750","pmid":"40556483","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10460","title":"Ratio of pulmonary artery diameter to ascending aortic diameter and its association with right ventricular failure after left ventricular assist device implantation.","authors":"Chimura, Misato; Ohtani, Tomohito; Sera, Fusako; Nakamoto, Kei; Akazawa, Yasuhiro; Kajitani, Kenji; Higuchi, Rie; Kagiya, Toshifumi; Sakata, Yasushi","year":2025,"journal":"International journal of cardiology, 418, 132596","doi":"10.1016/j.ijcard.2024.132596","pmid":"39326703","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10461","title":"The impact of glucagon-like peptide-1 receptor agonists on the quality indicators of colonoscopy - a systematic review and meta-analysis.","authors":"Chiu, Yu-Tse; Chen, Yu-Tsung; Lee, Fu-Jen; Chang, Chi-Yang","year":2025,"journal":"Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver, 57(7), 1386-1392","doi":"10.1016/j.dld.2025.03.004","pmid":"40121157","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10462","title":"Tetrapeptide from microbial coculture exhibiting a unique algicidal mechanism against Alexandrium fundyense.","authors":"Cho, Ja Young; Kim, Joong Kyun","year":2025,"journal":"Scientific reports, 15(1), 42505","doi":"10.1038/s41598-025-26569-x","pmid":"41309893","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10463","title":"Cortical Thickness Changes in Migraine Patients Treated with Anti-Calcitonin Gene-Related Peptide Monoclonal Antibodies: A Prospective Age- and Sex-Matched Controlled Study.","authors":"Cho, Soohyun","year":2025,"journal":"Biomedicines, 13(5)","doi":"10.3390/biomedicines13051150","pmid":"40426977","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10464","title":"Structural Plasticity of Peptidergic and Nonpeptidergic C Afferent Terminals in the Medullary Dorsal Horn during Craniofacial Inflammatory Pain.","authors":"Cho, Yi Sul; Kim, Yun Sook; Bae, Jin Young; Ahn, Dong Kuk; Yoshida, Atsushi; Bae, Yong Chul","year":2025,"journal":"The Journal of neuroscience : the official journal of the Society for Neuroscience, 45(50)","doi":"10.1523/JNEUROSCI.1346-25.2025","pmid":"41188029","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10465","title":"Engineered nutrient-stimulated hormonal multi-agonists for precision targeting of obesity and metabolic disorders.","authors":"Cho, Yun Kyung; Jung, Chang Hee","year":2025,"journal":"Clinical and molecular hepatology","doi":"10.3350/cmh.2025.0744","pmid":"41297910","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10466","title":"Metabolic Consequences of Glucagon-Like Peptide-1 Receptor Agonist Shortage: Deterioration of Glycemic Control in Type 2 Diabetes.","authors":"Choe, Hun Jee; Nauck, Michael A; Moon, Joon Ho","year":2025,"journal":"Endocrinology and metabolism (Seoul, Korea), 40(1), 156-160","doi":"10.3803/EnM.2024.2150","pmid":"39582250","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10467","title":"Low-Molecular-Weight Collagen Peptide Improves Skin Dehydration and Barrier Dysfunction in Human Dermal Fibrosis Cells and UVB-Exposed SKH-1 Hairless Mice.","authors":"Choi, Eunjung; Joo, Heeyeon; Kim, Myunghee; Kim, Do-Un; Chung, Hee-Chul; Kim, Jae Gon","year":2025,"journal":"International journal of molecular sciences, 26(13)","doi":"10.3390/ijms26136427","pmid":"40650202","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10468","title":"Changes in gene and protein expression related to feed intake and thermoregulation in broilers challenged with different doses of mixed Eimeria spp.","authors":"Choi, Janghan; Lee, Jihwan; Kim, Woo Kyun","year":2025,"journal":"Poultry science, 104(10), 105481","doi":"10.1016/j.psj.2025.105481","pmid":"40618565","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10469","title":"Comparative effectiveness of antidiabetic therapies on hepatic decompensation in patients with type 2 diabetes: A target trial emulation.","authors":"Choi, Jonggi; Verma, Ana; Nguyen, Vy H; Przybyszewski, Eric; Song, Jiunn; Carroll, Allison; Michta, Megan; Almazan, Erik; Simon, Tracey G; Chung, Raymond T","year":2025,"journal":"JHEP reports : innovation in hepatology, 7(12), 101624","doi":"10.1016/j.jhepr.2025.101624","pmid":"41362712","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 38,524 patients with type 2 diabetes:\n- GLP-1RAs reduced hepatic decompensation risk by 42% vs sulfonylureas (HR 0.58, 95% CI 0.38-0.88)\n- SGLT2is reduced risk by 35% vs sulfonylureas (HR 0.65, 95% CI 0.43-0.98)\n- GLP-1RAs reduced risk by 41% vs DPP4is (HR 0.59, 95% CI 0.39-0.89)\n- Per-protocol analysis showed even stronger GLP-1RA protection (HR 0.43, 95% CI 0.22-0.82, a 57% risk reduction)\n- No significant difference between GLP-1RAs and SGLT2is\n- 1,743 hepatic decompensation events occurred over median 3.1 years follow-up","whyItMatters":"Many patients with type 2 diabetes have undiagnosed fatty liver disease that can progress to serious liver failure. This study provides real-world evidence that GLP-1 peptide drugs don't just control blood sugar — they may also significantly protect the liver. For clinicians choosing between diabetes medications, this adds liver protection as another reason to prefer GLP-1 agonists, especially in patients with metabolic liver disease risk.","specificNumbers":"","methodology":"Retrospective new-user cohort study emulating a target trial using electronic health records from Mass General Brigham (2012-2024). 38,524 adults with T2DM who newly started one of four drug classes were included. Propensity score overlap weighting was used for covariate balance. Both intention-to-treat and per-protocol analyses were performed, with multiple sensitivity analyses.","limitations":"This is an observational retrospective study, not a randomized trial, so confounding cannot be entirely eliminated despite propensity score methods. The study used electronic health records from a single health system (Mass General Brigham), which may not represent all patient populations. Specific GLP-1RA drugs were not compared individually. The mechanisms driving liver protection were not investigated."},{"rthcId":"RPEP-10470","title":"Characterization and antimicrobial activity of a novel pleurocidin in starry flounder (Platichthys stellatus).","authors":"Choi, Mi-Jin; Jang, Hyun Seok; Oh, Young Dae; Jeon, Yu-Jeong; Kim, Jong-Myoung; Lim, Han Kyu","year":2025,"journal":"Fish & shellfish immunology, 163, 110420","doi":"10.1016/j.fsi.2025.110420","pmid":"40379117","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10471","title":"Semaglutide-induced weight loss improves mitochondrial energy efficiency in skeletal muscle.","authors":"Choi, Ran Hee; Karasawa, Takuya; Meza, Cesar A; Maschek, J Alan; Manuel, Allison M; Nikolova, Linda S; Fisher-Wellman, Kelsey H; Cox, James E; Chaix, Amandine; Funai, Katsuhiko","year":2025,"journal":"Obesity (Silver Spring, Md.), 33(5), 974-985","doi":"10.1002/oby.24274","pmid":"40254778","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide treatment led to significant reductions in both fat and lean mass in high-fat diet-fed mice. Skeletal muscle OXPHOS efficiency (ATP produced per O2 consumed) increased in permeabilized muscle fibers after semaglutide treatment. Mitochondrial proteomics revealed changes in only two proteins — LYRM7 and TTC19 — both linked to complex III assembly (p<0.05 without multiple testing corrections). No substantial changes in the abundance of OXPHOS subunits were observed, suggesting the efficiency gain comes from assembly optimization rather than increased mitochondrial content.","whyItMatters":"Weight regain after stopping GLP-1 agonists is one of the biggest clinical challenges in obesity medicine. Understanding the metabolic adaptations that promote regain is essential for developing strategies to maintain weight loss. This study identifies a specific mechanism — increased muscle mitochondrial efficiency — that reduces calorie burning during weight loss and may drive the body to regain weight when the drug's appetite-suppressing effects end.","specificNumbers":"","methodology":"C57BL/6J mice were fed a high-fat diet for 12 weeks to induce obesity, then received semaglutide or vehicle for 1 or 3 weeks. Skeletal muscle OXPHOS efficiency was measured using high-resolution respirometry and fluorometry in permeabilized muscle fibers, determining ATP production rates relative to oxygen consumption. Mitochondrial proteomics was performed to identify protein-level changes underlying the efficiency shift.","limitations":"This is a mouse study, and metabolic responses to semaglutide may differ in humans. The treatment periods (1 and 3 weeks) are short relative to typical human treatment courses. The proteomic changes reached significance only without multiple testing corrections, meaning they could be false positives. The study did not directly demonstrate that the efficiency increase causes weight regain — this is a hypothesis. Fat and lean mass were both reduced, but the relative contributions weren't fully characterized."},{"rthcId":"RPEP-10472","title":"Calcitonin Gene-Related Peptide Monoclonal Antibody Treatment in Nine Cases of Persistent Headache Following COVID-19-Infection.","authors":"Choi, Soyoun; Hong, Yooha; Kang, Mi-Kyoung; Song, Tae-Jin; Cho, Soo-Jin","year":2025,"journal":"Journal of Korean medical science, 40(25), e127","doi":"10.3346/jkms.2025.40.e127","pmid":"40589358","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10473","title":"Brain activity associated with breakthrough food preoccupation in an individual on tirzepatide.","authors":"Choi, Wonkyung; Nho, Young-Hoon; Qiu, Liming; Chang, Andrew; Campos, Gustavo; Seilheimer, Robert L; Wilent, W Bryan; Bakalov, David; Firdous, Nida; Kerr, Marie; Joshi, Disha; Maze, Gabriella; Topalovic, Uros; Batista, Daniel; Suthana, Nanthia; Amaro, Anastassia; Hayes, Matthew R; Cajigas, Iahn; Cristancho, Mario; Allison, Kelly C; Pesaran, Bijan; Scangos, Katherine W; Gold, Joshua I; Wadden, Thomas A; Halpern, Casey H","year":2025,"journal":"Nature medicine, 31(12), 4038-4043","doi":"10.1038/s41591-025-04035-5","pmid":"41249493","tags":[],"studyType":"case study","evidenceStrength":"very low","keyFinding":"In a first-in-human investigation, researchers recorded electrical activity directly from the nucleus accumbens — a key brain reward center — of a patient taking tirzepatide (a dual GIP/GLP-1 receptor agonist used for obesity). After starting tirzepatide, the patient experienced increased episodes of severe food preoccupation. These episodes were preceded by a surge in slow-wave (delta-theta, ≤7 Hz) brain activity in the nucleus accumbens, suggesting that the drug modulates reward circuitry in ways that may paradoxically intensify food-related thoughts in some individuals.","whyItMatters":"GLP-1-based drugs like tirzepatide are widely prescribed for obesity and are known to reduce appetite and food intake. However, their effects on the brain's reward system are poorly understood because directly recording from deep brain structures in living humans is exceptionally rare. This case provides the first direct electrophysiological evidence of how an incretin therapy engages the mesolimbic reward pathway, and the unexpected finding of increased food preoccupation challenges simple assumptions about how these drugs work in the brain.","specificNumbers":"n=1, delta-theta frequency ≤7 Hz power increase in nucleus accumbens preceding food preoccupation episodes","methodology":"Researchers recorded electrophysiology directly from electrodes implanted in the nucleus accumbens of a single patient-participant with obesity who was prescribed tirzepatide. They monitored brain activity patterns before, during, and after episodes of food preoccupation, identifying characteristic changes in delta-theta frequency power that preceded these episodes.","limitations":"This is a single-patient case report, so the findings cannot be generalized to the broader population taking tirzepatide or other incretin-based therapies. The patient already had electrodes implanted in the nucleus accumbens (likely for another clinical indication), making them a highly atypical case. The short-term course of tirzepatide may not reflect long-term brain adaptations. Causal relationships cannot be established from observational data in one individual."},{"rthcId":"RPEP-10474","title":"Marmoset superior colliculus: neuronal expression of somatostatin but not vasoactive intestinal peptide or neuropeptide Y.","authors":"Chong, Melissa H Y; Cho, Emmanuel K L; Rosa, Marcello G P; Atapour, Nafiseh","year":2025,"journal":"Frontiers in neuroanatomy, 19, 1731419","doi":"10.3389/fnana.2025.1731419","pmid":"41458172","tags":[],"studyType":"basic-research","evidenceStrength":"low","keyFinding":"In the marmoset monkey superior colliculus (a midbrain structure that directs eye and head movements), somatostatin-expressing neurons were found across all cellular layers, accounting for approximately 3–5% of total neurons. These somatostatin-positive neurons were confirmed to be inhibitory (GABAergic), with the highest density (~3,140/mm³) in the top layer (stratum griseum superficiale), decreasing deeper into the structure.\n\nNotably, neither vasoactive intestinal peptide (VIP) nor neuropeptide Y (NPY) were found in any neurons in the superior colliculus, despite being clearly present in neighboring brain structures on the same tissue sections.","whyItMatters":"Understanding which neuropeptides are expressed in specific brain regions helps neuroscientists build a complete cell-type map of the brain. The finding that somatostatin — but not VIP or NPY — is present in the primate superior colliculus adds important data about how this visually-important brain structure is organized, and how it may differ from rodent models commonly used in research.","specificNumbers":"SST+ neurons: 3–5% of total · ~3,140/mm³ in top layer · VIP: absent · NPY: absent","methodology":"Researchers used immunostaining techniques on brain tissue from adult marmoset monkeys (Callithrix jacchus) to detect three neuropeptides: somatostatin (SST), vasoactive intestinal peptide (VIP), and neuropeptide Y (NPY). Neuronal density was estimated using stereological sampling methods. Co-staining with GABA confirmed the inhibitory nature of somatostatin-positive neurons. Staining specificity was validated by confirming VIP and NPY neurons in adjacent brain structures.","limitations":"This is a neuroanatomy mapping study in marmosets — findings may not directly translate to humans, though marmosets are primates. The study characterizes presence/absence and density but does not explore functional roles of somatostatin in the superior colliculus. Sample size of animals is not specified in the abstract."},{"rthcId":"RPEP-10475","title":"Hypothalamic regulation of obesity: Revealing the therapeutic potential of a novel anti-obesity peptide.","authors":"Choo, Yi Ning; Narayanan, Ram; Subramaniyan, Vetriselvan","year":2025,"journal":"Vascular pharmacology, 161, 107553","doi":"10.1016/j.vph.2025.107553","pmid":"41093047","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10476","title":"Importance of chirality in the self-organizing peptides - from single molecules to functional supramolecular structures.","authors":"Chotera-Ouda, Agata; Trzeciak, Katarzyna; Potrzebowski, Marek J","year":2025,"journal":"Physical chemistry chemical physics : PCCP, 27(35), 18062-18092","doi":"10.1039/d5cp01562f","pmid":"40833397","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10477","title":"Association between Semaglutide and Nonarteritic Anterior Ischemic Optic Neuropathy: A Multinational Population-Based Study.","authors":"Chou, Chien-Chih; Pan, Ssu-Yu; Sheen, Yi-Jing; Lin, Jun-Fu; Lin, Ching-Heng; Lin, Hui-Ju; Wang, I-Jong; Weng, Chien-Hsiang","year":2025,"journal":"Ophthalmology, 132(4), 381-388","doi":"10.1016/j.ophtha.2024.10.030","pmid":"39491755","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10478","title":"Comparison of New-Onset Peripheral Artery Disease in Patients With Type 2 Diabetes Exposed to Sodium-Glucose Cotransporter-2 Inhibitors, Dipeptidyl Peptidase-4 Inhibitors, or Glucagon-Like Peptide-1 Agonists: A Population-Based Cohort Study.","authors":"Chou, Oscar Hou-In; Luo, Zhiyao; Chung, Cheuk To Skylar; Chan, Jeffrey; Li, Huixian; Lakhani, Ishan; Lee, Sharen; Lau, Dawnie Ho Hei; Zhang, Qingpeng; Liu, Tong; Wong, Wing Tak; Cheung, Bernard Man Yung; Lip, Gregory Y H; Leung, Fung Ping; Tse, Gary; Zhou, Jiandong","year":2025,"journal":"Journal of the American Heart Association, 14(11), e034175","doi":"10.1161/JAHA.123.034175","pmid":"40401622","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In a propensity-matched cohort of 75,470 patients with type 2 diabetes followed for a median of 5.6 years, SGLT2 inhibitor users had a significantly lower risk of new-onset peripheral artery disease compared to DPP4 inhibitor users (HR 0.79, 95% CI 0.66–0.93). In a three-arm analysis, the risk of PAD was not statistically different between SGLT2 inhibitors and GLP-1 receptor agonists (HR 1.18, 95% CI 0.52–2.68), suggesting both newer drug classes offer similar vascular protection. The findings remained consistent across subgroups regardless of sex, age, or comorbid metabolic diseases.","whyItMatters":"Peripheral artery disease is a major cause of disability and amputation in diabetes patients. This large real-world study suggests that choosing SGLT2 inhibitors or GLP-1 receptor agonists over DPP4 inhibitors may provide additional vascular protection, potentially influencing treatment selection for patients at risk of PAD.","specificNumbers":"n=75,470 · SGLT2I: 28,753 · DPP4I: 46,717 · PAD HR 0.79 (SGLT2I vs DPP4I) · 95% CI 0.66–0.93 · median follow-up 5.6 years · GLP-1 RA vs SGLT2I HR 1.18 (not significant)","methodology":"Retrospective population-based cohort study using a territory-wide electronic health database from Hong Kong. Patients with type 2 diabetes prescribed SGLT2 inhibitors or DPP4 inhibitors between January and December 2015 were included. Propensity score matching (1:1) was used to balance baseline characteristics. Multivariable Cox regression with time-weighted variables identified associations. A three-arm analysis added a GLP-1 receptor agonist cohort. Competing risk and sensitivity analyses were performed.","limitations":"This is an observational study, so it cannot prove causation — only association. The GLP-1 receptor agonist cohort was much smaller, resulting in wide confidence intervals for that comparison. As a Hong Kong-based study, the predominantly Chinese population may limit generalizability. Residual confounding from unmeasured variables is possible despite propensity matching."},{"rthcId":"RPEP-10479","title":"Precision Antimicrobial Therapy Against Fusobacterium nucleatum Using Bioengineered Probiotics Expressing Guided Antimicrobial Peptides (gAMPs).","authors":"Choudhury, Ankan; Scano, Colin; Barton, Allison; Kearney, Christopher M; Greathouse, K Leigh","year":2025,"journal":"Microbial biotechnology, 18(12), e70241","doi":"10.1111/1751-7915.70241","pmid":"41368940","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10480","title":"Exploring the Effect of Hydrocarbon Cross-Linkers on the Structure and Binding of Stapled p53 Peptides.","authors":"Choudhury, Asha Rani; Gaikwad, Vikram; Maity, Atanu; Chakrabarti, Rajarshi","year":2025,"journal":"Proteins, 93(6), 1090-1106","doi":"10.1002/prot.26793","pmid":"39754310","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10481","title":"In Silico Peptide Design: Methods, Resources, and Role of AI.","authors":"Choudhury, Priyanka Ray; Mishra, Sai Kumar; Yadav, Siddharth; Singh, Shubhi; Mathur, Puniti","year":2025,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 31(12), e70063","doi":"10.1002/psc.70063","pmid":"41168660","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies three major computational approaches accelerating peptide design: structure-based design (modeling how peptides interact with their targets), molecular dynamics simulations (watching peptide behavior over time), and ligand-based approaches (learning from known active peptides). Machine learning and deep learning methods are increasingly central, with generative AI models now capable of proposing entirely novel peptide sequences. However, key challenges remain: training data is often inconsistent across databases, AI model predictions can be difficult to interpret, and the physics simulations (forcefields) used to model peptide behavior still need improvement.","whyItMatters":"Peptide therapeutics are one of the fastest-growing drug classes, but designing them traditionally required years of synthesis and screening. Computational and AI methods are compressing this timeline dramatically, potentially making peptide drugs cheaper and faster to develop. This matters for patients because it accelerates the pipeline for new treatments across cancer, infectious disease, metabolic disorders, and more.","specificNumbers":"","methodology":"This is a comprehensive review article that surveys the current landscape of computational peptide design. It covers peptide databases, computational tools, structure-based and ligand-based design methods, molecular dynamics simulations, and AI/ML approaches including deep learning and generative models.","limitations":"As a review, this paper synthesizes existing methods rather than presenting new experimental results. The authors note that training data inconsistency across databases remains a significant barrier, AI model interpretability is limited (many models act as 'black boxes'), and molecular dynamics forcefields still don't perfectly capture peptide behavior. The gap between computational predictions and real-world drug performance remains substantial."},{"rthcId":"RPEP-10482","title":"Focal Adhesion Kinase Inhibition Ameliorates Burn Injury-Induced Chronic Pain in Rats.","authors":"Chouhan, Deepak; Akhilesh; Tiwari, Vinod","year":2025,"journal":"Molecular neurobiology, 62(4), 4466-4483","doi":"10.1007/s12035-024-04548-z","pmid":"39460902","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10483","title":"Unearthing novel and multifunctional peptides in peptidome of fermented chhurpi cheese of Indian Himalayan region.","authors":"Chourasia, Rounak; Abedin, Md Minhajul; Phukon, Loreni Chiring; Sarkar, Puja; Sharma, Swati; Sahoo, Dinabandhu; Singh, Sudhir Pratap; Kumar Rai, Amit","year":2025,"journal":"Food research international (Ottawa, Ont.), 201, 115651","doi":"10.1016/j.foodres.2024.115651","pmid":"39849787","tags":["food-derived-peptides","ace-inhibitors"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Researchers identified novel bioactive peptides from chhurpi — a traditional fermented cheese from the Indian Himalayas — that can inhibit ACE (angiotensin-converting enzyme, a key blood pressure regulator) and reduce oxidative stress markers. Two synthesized peptides stood out: LKPTPEGDL showed the most potent ACE inhibitory activity with an IC50 of 25.82 µmol, while HPHPHLSFM showed superior antioxidant activity by reducing hypochlorous acid (HOCl) with an EC50 of 0.29 mmol.\n\nBoth peptides also inhibited myeloperoxidase (MPO), an enzyme linked to inflammation and oxidative damage. The ACE inhibition worked through a non-competitive mixed mechanism, and the peptides retained activity even after simulated gastrointestinal digestion — a critical requirement for any food-derived peptide to be useful.","whyItMatters":"Food-derived peptides that lower blood pressure naturally are a growing area of research, with some (like lactotripeptides from milk) already in commercial supplements. This study expands the search to an underexplored source — traditional Himalayan fermented cheese — and identifies peptides with dual blood-pressure-lowering and antioxidant properties. The fact that these peptides survive digestion makes them potentially viable as functional food ingredients.","specificNumbers":"","methodology":"Researchers fermented chhurpi cheese using native Lactobacillus delbrueckii WS4 bacteria and analyzed the peptide content across different stages of simulated gastrointestinal digestion. They used computational tools to predict ACE inhibitory potential, then synthesized the most promising peptides and validated their activity in vitro. Testing included ACE inhibition assays, HOCl reduction, MPO inhibition, and molecular docking simulations to understand binding mechanisms.","limitations":"This is entirely in vitro and in silico work — no animal or human studies were conducted. Lab-based ACE inhibition doesn't guarantee blood pressure reduction in living systems. The peptide concentrations achievable through eating cheese may be far below therapeutic levels. Bioavailability in humans (absorption, distribution, metabolism) remains unknown."},{"rthcId":"RPEP-10484","title":"Calcitonin Gene-Related Peptide Antagonist Use and Atypical Femur Fractures: A Case Report.","authors":"Choy, Kenneth; McDonald, Jason J; Geiselmann, Matthew; Daubs, Gregory","year":2025,"journal":"JBJS case connector, 15(3)","doi":"10.2106/JBJS.CC.25.00148","pmid":"40638759","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A 56-year-old woman on erenumab (a CGRP receptor antagonist monoclonal antibody) for migraine prevention presented with bilateral atypical femur fractures (AFFs) after a mechanical fall. Imaging showed lateral cortical beaking — a hallmark of stress-related atypical fractures typically associated with bisphosphonate use. She required bilateral femoral intramedullary nailing.\n\nThe authors note that CGRP has roles in bone biology and that blocking it may affect bone formation, potentially linking CGRP antagonist therapy to atypical fracture risk. This appears to be an early report raising this safety concern.","whyItMatters":"Millions of migraine patients use CGRP-targeting peptide antibodies (erenumab, fremanezumab, galcanezumab), and atypical femur fractures are a serious, potentially disabling complication. CGRP is known to play a role in bone metabolism — it's not just a pain signaling molecule. If CGRP antagonism disrupts normal bone remodeling, this could represent a significant long-term safety concern for a drug class used chronically by a predominantly young female population already at risk for osteoporosis.","specificNumbers":"1 patient · 56 years old · Bilateral AFFs · Lateral cortical beaking · Erenumab (CGRP antagonist) · Bilateral intramedullary nailing required","methodology":"Single case report describing a 56-year-old woman with bilateral atypical femur fractures identified on imaging after a fall. Medical history review identified erenumab use for migraine prevention. Treatment was bilateral femoral intramedullary nailing followed by rehabilitation.","limitations":"Single case report (n=1) cannot establish causation between erenumab and atypical fractures. Other risk factors for AFFs (bisphosphonate use, vitamin D status, bone density) may not have been fully reported. The patient's fall was the proximate cause of fracture, though AFFs are stress fractures where the fall may simply complete an already weakened bone. No population-level data on fracture rates in CGRP antagonist users is available."},{"rthcId":"RPEP-10485","title":"Structural regression modelling of peptide based drug delivery vectors for targeted anti-cancer therapy.","authors":"Christian, Yvonne; Redkar, Amay Sanjay; Kumar, Naveen; Jancy, Shine Varghese; Chandrasekharan, Aneesh; Retnabai Santhoshkumar, Thankayyan; Ramakrishnan, Vibin","year":2025,"journal":"Drug delivery and translational research, 15(4), 1284-1298","doi":"10.1007/s13346-024-01674-y","pmid":"39117921","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10486","title":"Ex vivo stimulation of the trigeminal nucleus caudalis induces peripheral CGRP release in the trigeminal ganglion and reveals a distinct dopamine-endocannabinoid mechanism relevant to migraine.","authors":"Christiansen, Isabella Mai; Reducha, Philip Victor; Edvinsson, Lars; Holm, Anja; Haanes, Kristian Agmund","year":2025,"journal":"The journal of headache and pain, 26(1), 141","doi":"10.1186/s10194-025-02072-6","pmid":"40524163","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10487","title":"Last decade of advances in gastric neuroendocrine tumors: Innovations, challenges, and future directions.","authors":"Christodoulidis, Grigorios; Kouliou, Marina Nektaria; Ragias, Dimitrios; Chatziisaak, Dimitrios; Agko, Eirini Sara; Schizas, Dimitrios; Zacharoulis, Dimitrios","year":2025,"journal":"World journal of clinical oncology, 16(5), 104577","doi":"10.5306/wjco.v16.i5.104577","pmid":"40503415","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10488","title":"Repurposed versus disease-specific medicinals for the prophylaxis of migraine: an updated systematic review.","authors":"Christofilos, Savvas-Ilias; Mavridis, Theodoros; Gkotzamanis, Viktor; Vasilopoulou, Sofia; Deligianni, Christina I; Mitsikostas, Dimos-Dimitrios","year":2025,"journal":"Pain management, 15(7), 425-439","doi":"10.1080/17581869.2025.2509474","pmid":"40447296","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10489","title":"Glucagon-like Peptide-1 Receptor Agonists (GLP-1 RAs): A Pan-Steatotic Liver Disease Treatment?","authors":"Chrysavgis, Lampros; Mourelatou, Niki-Gerasimoula; Cholongitas, Evangelos","year":2025,"journal":"Biomedicines, 13(7)","doi":"10.3390/biomedicines13071516","pmid":"40722592","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10490","title":"The Influence of Glucagon-like Peptide-1 Receptor Agonists and Other Incretin Hormone Agonists on Body Composition.","authors":"Chrysavgis, Lampros; Mourelatou, Niki Gerasimoula; Koloutsou, Maria-Evangelia; Rozani, Sophia; Cholongitas, Evangelos","year":2025,"journal":"International journal of molecular sciences, 26(24)","doi":"10.3390/ijms262412130","pmid":"41465555","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1-based therapies predominantly reduce adipose tissue, including visceral and ectopic fat depots, but they also produce absolute reductions in lean mass representing 20-30% of total weight loss. This ratio is generally consistent with the lean-to-fat loss ratio seen with other forms of weight loss.\n\nThe review highlights sarcopenia (age-related muscle loss) and sarcopenic obesity as conditions of particular concern, given their overlap with the populations being treated with GLP-1 drugs. Data on dual and triple agonists (tirzepatide, retatrutide) are emerging but remain limited. The extent to which lean mass reduction translates into impaired muscle function or increased frailty vulnerability remains unclear.","whyItMatters":"Millions of people are using GLP-1 receptor agonists for weight loss, and many will lose significant amounts of lean tissue along with fat. For older adults, those with limited mobility, or patients who are already losing muscle with age, this lean mass loss could increase fall risk, reduce independence, and accelerate frailty. Understanding and mitigating this risk is essential for safe long-term use of these peptide drugs.","specificNumbers":"","methodology":"This is a narrative review integrating physiological, clinical, and mechanistic perspectives from preclinical studies and randomized clinical trials. It covers the physiology of incretin hormones, their potential relevance to muscle health, body composition changes during GLP-1 therapy, and the clinical implications of lean mass loss.","limitations":"Current studies are constrained by methodological heterogeneity in body composition measurement, small sample sizes, and limited assessment of functional outcomes (strength, physical performance). Most trials report total lean mass changes without differentiating skeletal muscle from other lean tissue. Data on dual and triple agonists are still very limited. The review does not include a systematic search or meta-analysis."},{"rthcId":"RPEP-10491","title":"Use of Second-line Diabetes Mellitus Medications and Adverse Events Among Older Adults After the Introduction of Glucagon-like Peptide-1 Receptor Agonists in Ontario, Canada: A Retrospective Cohort Study.","authors":"Chu, Cherry; Ghahramani, Dorsa; Giannakeas, Vasily; Jeyaparan, Jeyani; Bhattacharyya, Onil; Gomes, Tara; Ivers, Noah; Tadrous, Mina","year":2025,"journal":"Canadian journal of diabetes","doi":"10.1016/j.jcjd.2025.12.009","pmid":"41418910","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10492","title":"Efficacy of lifestyle modification combined with GLP-1 receptor agonists on body weight and cardiometabolic biomarkers in individuals with overweight or obesity: a systematic review and meta-analysis.","authors":"Chu, Jiaheng; Zhang, Haibo; Wu, Yin; Huang, Yue; Zhu, Tianren; Zhou, Ziyi; Wang, Hui","year":2025,"journal":"EClinicalMedicine, 88, 103464","doi":"10.1016/j.eclinm.2025.103464","pmid":"40926900","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10493","title":"Catestatin as a predictor for cardiac death in heart failure with mildly reduced and preserved ejection fraction.","authors":"Chu, Song-Yun; Peng, Fen; Wang, Jie; Liu, Lin; Zhao, Jing; Han, Xiao-Ning; Ding, Wen-Hui","year":2025,"journal":"ESC heart failure, 12(1), 517-524","doi":"10.1002/ehf2.15107","pmid":"39359227","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10494","title":"The effectiveness and safety of integrative medicine for chronic heart failure: An umbrella review.","authors":"Chua, Wei J; Liu, Jing; Lam, Kaitlyn; Maunder, Alison; Pandey, Chhiti; Cave, Adele E; O'Fee, Allana; Yang, Guoyan; Mousa, Aya; Ee, Carolyn","year":2025,"journal":"Complementary therapies in medicine, 91, 103182","doi":"10.1016/j.ctim.2025.103182","pmid":"40287103","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10495","title":"Early GLP-1 Agonist Use and Cancer Risk in Type 2 Diabetes: A Real-World Data Cohort Study.","authors":"Chuang, Cheng-Hsun; Tsai, Ping-Kun; Kao, Shih-Wen; Wang, Yu-Hsun; Yeh, Chao-Bin","year":2025,"journal":"Oncology research, 34(1), 12","doi":"10.32604/or.2025.072875","pmid":"41502515","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10496","title":"Exploring the link between GLP-1 receptor agonists and dementia: A comprehensive review.","authors":"Chuansangeam, Mallika; Phadungsaksawasdi, Pawit; Park, Hyo Jin; Yang, Yuan-Han","year":2025,"journal":"Journal of Alzheimer's disease reports, 9, 25424823251342182","doi":"10.1177/25424823251342182","pmid":"40370762","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10497","title":"Viral insulin/IGF-like peptides inhibit IGF-1 receptor signaling to enhance viral replication.","authors":"Chuard, Aurelien; Nesarajah, Kalaimagal; Danazumi, Khadija; Reiners, Kaitlin; Zhang, Fa; Levintov, Lev; Lubos, Marta; Žáková, Lenka; Ruggera, Rachel; McMenamin, Sarah; Vashisth, Harish; Jiráček, Jiří; Dimarchi, Richard; Altindis, Emrah","year":2025,"journal":"Cell reports, 44(8), 116149","doi":"10.1016/j.celrep.2025.116149","pmid":"40829596","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Viral insulin/IGF-1-like peptides (VILPs) from grouper iridovirus (GIV) are early viral genes that are secreted during infection. Key findings:\n\n- VILPs activate both insulin receptor (IR) and IGF-1 receptor (IGF1R) phosphorylation and the PI3K pathway\n- GIV-VILP selectively interacts with IGF1R in a dose- and time-dependent manner\n- Paradoxically: IR inhibition suppresses viral replication, while IGF1R inhibition enhances it, and IGF-1 stimulation reduces replication\n- VILPs compete with host IGF-1, attenuating IGF1R signaling and reducing cell proliferation\n- This viral mimicry mechanism was confirmed in a zebrafish infection model with transcriptome analysis showing negative regulation of cell cycle pathways","whyItMatters":"This reveals an entirely new strategy viruses use to manipulate their hosts — producing fake insulin-like peptides. Understanding viral peptide mimicry has implications for virology, immunology, and potentially metabolic disease, as these viral peptides could theoretically affect metabolic signaling in infected organisms.","specificNumbers":"","methodology":"Researchers used grouper iridovirus on grouper and zebrafish cells, characterizing VILP expression timing, secretion, and receptor activation. Receptor-specific inhibitors and IGF-1 stimulation experiments determined the functional effects on viral replication. Transcriptome analysis and a zebrafish in vivo model validated the signaling mechanism.","limitations":"The study focused on fish iridoviruses, and it's unknown whether mammalian viruses employ similar insulin-like peptide mimicry strategies. The functional studies were primarily in fish cell lines and zebrafish, limiting direct human health relevance. The precise structural basis for VILPs' selective receptor interactions needs further characterization."},{"rthcId":"RPEP-10498","title":"Weight and body composition outcomes with liraglutide in individuals with well-treated hypothyroidism: A retrospective case-control study.","authors":"Chukir, Tariq; Yaghmour, Mohammad; Almutairi, Turki; Chagoury, Odette; Taheri, Shahrad","year":2025,"journal":"PloS one, 20(9), e0332091","doi":"10.1371/journal.pone.0332091","pmid":"40934243","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10499","title":"Weight loss and body composition after compounded semaglutide treatment in a real world setting.","authors":"Chun, Elizabeth; Siojo, Alexandra; Rivera, David; Reyna, Kirsten; Legere, Henry; Joseph, Richard; Pojednic, Rachele","year":2025,"journal":"Diabetes, obesity & metabolism, 27(3), 1536-1543","doi":"10.1111/dom.16162","pmid":"39776038","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"After 3 months on compounded semaglutide/cyanocobalamin, 94 participants lost an average of 4.11 kg (4.57% of body weight). Fat mass decreased by 2.67 kg and trunk fat by 1.10 kg. Lean mass decreased by 1.43 kg and skeletal muscle by 0.88 kg in absolute terms, but as a proportion of total body weight, lean and skeletal muscle mass actually increased while fat mass proportion decreased. This demonstrates that body composition improved despite some absolute lean mass loss.","whyItMatters":"Compounded semaglutide has become widely used outside the brand-name pharmaceutical supply chain, but real-world effectiveness data has been scarce. This study shows that compounded semaglutide produces meaningful weight loss in a commercial setting, and importantly provides body composition data addressing the concern that GLP-1 drugs may cause excessive muscle loss.","specificNumbers":"n=94 · avg weight loss 4.11 kg (4.57%) at 3 months · fat loss 2.67 kg · trunk fat loss 1.10 kg · lean mass loss 1.43 kg · skeletal muscle loss 0.88 kg · dose range 0.25–2.4 mg/week","methodology":"Retrospective study of 94 individuals in a commercial weight management programme at a wellness studio from June 2023 to January 2024. Participants received weekly subcutaneous compounded semaglutide/cyanocobalamin injections starting at 0.25 mg/0.125 mg and titrated up to 2.4 mg/0.24 mg. Weight and body composition were measured at baseline and 3 months.","limitations":"This is a retrospective study with no control group, so it's impossible to isolate the effect of semaglutide from other programme components like dietary counseling. The sample was predominantly female (86%) and from a commercial wellness studio, which may not represent the general population. The 3-month follow-up is relatively short. Compounded semaglutide is not FDA-approved and may differ from brand-name formulations."},{"rthcId":"RPEP-10500","title":"Superior Cerebrovascular Outcomes with Tirzepatide versus Semaglutide in Diabetic CABG Patients: A Global Network Study of Propensity-Matched Patients.","authors":"Chunduri, Shriya; Bidaoui, Ghassan; Hussein, Mohammad H; Patel, Milee; Abdelmaksoud, Ahmed; Mohamed, Mohamed; Attia, Abdallah; Tatum, Danielle; Borgi, Jamil; Toraih, Eman A","year":2025,"journal":"Cardiovascular drugs and therapy","doi":"10.1007/s10557-025-07757-3","pmid":"40938549","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10501","title":"Therapeutic potential of phytochemical luteolin in restoring skin barrier by inhibiting antimicrobial peptides associated with TRAF6/TAK1/IKK/IκB in psoriasis-like HaCaT models.","authors":"Chung, Hui Su; Hwang, Hyung Seo","year":2025,"journal":"Food science and biotechnology, 34(12), 2909-2921","doi":"10.1007/s10068-025-01894-z","pmid":"40655288","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10502","title":"Tooth Pulp Afferents and Transient Receptor Potential (TRP) Ion Channels as Key Regulators of Pulp Homeostasis, Inflammation, and Pain.","authors":"Chung, Man-Kyo; Raman, Swarnalakshmi; Szallasi, Arpad","year":2025,"journal":"International journal of molecular sciences, 27(1)","doi":"10.3390/ijms27010182","pmid":"41516061","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10503","title":"Prediction of peptide cleavage sites using protein language models and graph neural networks.","authors":"Cifuentes, Paula; Adàlia, Ramon; Zamora, Ismael","year":2025,"journal":"Scientific reports, 15(1), 38048","doi":"10.1038/s41598-025-21801-0","pmid":"41168342","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10504","title":"Saving muscle while losing weight: A vital strategy for sustainable results while on glucagon-like peptide-1 related drugs.","authors":"Cigrovski Berkovic, Maja; Ruzic, Lana; Cigrovski, Vjekoslav; Strollo, Felice","year":2025,"journal":"World journal of diabetes, 16(9), 109123","doi":"10.4239/wjd.v16.i9.109123","pmid":"40980310","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10505","title":"AMPEC4: Naja ashei Venom-Derived Peptide as a Stimulator of Fibroblast Migration with Antibacterial Activity.","authors":"Ciszkowicz, Ewa; Miłoś, Anna; Łyskowski, Andrzej; Buczkowicz, Justyna; Nieczaj, Anna; Lecka-Szlachta, Katarzyna; Hus, Konrad K; Sikora, Karol; Neubauer, Damian; Bauer, Marta; Kamysz, Wojciech; Bocian, Aleksandra","year":2025,"journal":"Molecules (Basel, Switzerland), 30(10)","doi":"10.3390/molecules30102167","pmid":"40430339","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10506","title":"Indirect comparative efficacy and safety of tirzepatide 10 and 15 mg versus semaglutide 2.4 mg for the management of obesity and overweight in patients with type 2 diabetes.","authors":"Ciudin, Andreea; Johansson, Erin; Zimner-Rapuch, Sarah; Dimitriadis, Georgios K; Bertrand, Marine; Curteis, Tristan; Clark, Laura J; Fan, Ludi; Sapin, Helene; Bergmann, Jean-Francois","year":2025,"journal":"Diabetes, obesity & metabolism, 27(9), 4709-4719","doi":"10.1111/dom.16508","pmid":"40537987","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10507","title":"Dorso lateral prefrontal cortex stimulation with TMS in chronic migraine individuals refractory to anti-CGRP monoclonal antibodies: Clinical, neuropsychological and neurophysiological effects.","authors":"Clemente, Livio; Paparella, Giulia; Scannicchio, Stefania; Abbatantuono, Chiara; Tancredi, Giusy; Ladisa, Emanuella; Delussi, Marianna D; Ammendola, Elena; Prudenzano, Addolorata Maria Pia; de Tommaso, Marina","year":2025,"journal":"Cephalalgia : an international journal of headache, 45(9), 3331024251364843","doi":"10.1177/03331024251364843","pmid":"40961282","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10508","title":"Predicting cardiac and renal responses to sacubitril/valsartan with a mathematical model of heart failure with preserved ejection fraction.","authors":"Clemmer, John S; Hall, Michael E; Mallette, Jordan H; Pruett, W Andrew","year":2025,"journal":"American journal of physiology. Heart and circulatory physiology, 329(4), H825-H837","doi":"10.1152/ajpheart.00223.2025","pmid":"40833871","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10509","title":"Semaglutide effects on safety and cardiovascular outcomes in patients with overweight or obesity: a systematic review and meta-analysis.","authors":"Cleto, André Saad; Schirlo, João Matheus; Beltrame, Mayara; Gomes, Victor Hugo Oliveira; Acras, Isabela Hellmann; Neiverth, Guinter Sponholz; Silva, Breno Bach; Juliatto, Beatriz Moreira Salles; Machozeki, Janete; Martins, Camila Marinelli","year":2025,"journal":"International journal of obesity (2005), 49(1), 21-30","doi":"10.1038/s41366-024-01646-9","pmid":"39396098","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The meta-analysis found statistically significant reductions across multiple cardiovascular endpoints:\n\n- Hospitalization for heart failure: RR 0.24 (95% CI 0.12–0.57), a 76% reduction\n- Cardiovascular death: RR 0.83 (95% CI 0.71–0.98), a 17% reduction\n- All-cause death: RR 0.79 (95% CI 0.70–0.89), a 21% reduction\n- Non-fatal myocardial infarction: RR 0.76 (95% CI 0.66–0.88), a 24% reduction\n- Coronary revascularization: RR 0.76 (95% CI 0.69–0.85), a 24% reduction\n- Stroke in diabetic patients: RR 0.65 (95% CI 0.44–0.97), a 35% reduction\n\nSubcutaneous administration showed stronger cardiovascular effects than oral semaglutide (subgroup difference p=0.05). Semaglutide was associated with a higher relative risk of most adverse effects evaluated, though treatment discontinuation rates were only significantly higher for oral semaglutide.","whyItMatters":"Cardiovascular disease is the leading cause of death among people with obesity, and finding drugs that reduce both weight and heart disease risk is a major clinical priority. This meta-analysis provides the most comprehensive evidence to date that semaglutide delivers meaningful cardiovascular protection — including a remarkable 76% reduction in heart failure hospitalizations. These findings support using semaglutide not just for weight management but as a cardiovascular protective therapy.","specificNumbers":"","methodology":"This was a systematic review and meta-analysis searching PubMed, LILACS, SciELO, Scopus, Web of Science, and the Cochrane Library. From 3,333 initial articles, 38 studies were included. Relative risk (RR) with 95% confidence intervals was calculated for cardiovascular outcomes and adverse effects. Heterogeneity was assessed using I² statistics. Subgroup analyses compared subcutaneous vs. oral administration routes and different oral doses.","limitations":"The heart failure hospitalization finding, while dramatic (76% reduction), was based on only 2 studies with 1,045 participants total, limiting confidence. Some outcomes showed moderate heterogeneity (I² up to 0.66 for stroke). The meta-analysis included studies with different follow-up durations, semaglutide doses, and patient populations. The association with more adverse effects — particularly gastrointestinal — may affect real-world adherence. The analysis combined diabetes and non-diabetes populations for most outcomes."},{"rthcId":"RPEP-10510","title":"Can Peripheral Arterial Tonometry and Biomarkers Help Identify Women Who Will Have Progressively Worsening Hypertensive Disorders of Pregnancy?","authors":"Clifford, Caitlin M; Hesson, Ashley M; Sangtani, Ajleeta; Ganesh, Santhi K; Langen, Elizabeth S","year":2025,"journal":"American journal of perinatology, 42(4), 511-519","doi":"10.1055/a-2407-1761","pmid":"39348828","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10511","title":"The probiotic Lacticaseibacillus rhamnosus GG supplementation reduces Salmonella load and modulates growth, intestinal morphology, gut microbiota, and immune responses in chickens.","authors":"Closs, Gary; Bhandari, Menuka; Helmy, Yosra A; Kathayat, Dipak; Lokesh, Dhanashree; Jung, Kwonil; Suazo, Isidora D; Srivastava, Vishal; Deblais, Loic; Rajashekara, Gireesh","year":2025,"journal":"Infection and immunity, 93(5), e0042024","doi":"10.1128/iai.00420-24","pmid":"40172512","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10512","title":"Prohormone cleavage prediction uncovers a non-incretin anti-obesity peptide.","authors":"Coassolo, Laetitia; B Danneskiold-Samsøe, Niels; Nguyen, Quennie; Wiggenhorn, Amanda; Zhao, Meng; Wang, David Cheng-Hao; Toomer, David; Lone, Jameel; Wei, Yichao; Patel, Aayan; Liparulo, Irene; Kavi, Deniz; Wat, Lianna W; Reghupaty, Saranya Chidambaranathan; Kim, Julie Jae; Asemi, Tina; Bielczyk-Maczynska, Ewa; Li, Veronica L; Moya-Garzon, Maria Dolores; Krentz, Nicole A J; Stahl, Andreas; Chou, Danny Hung-Chieh; Luo, Liqun; Svensson, Katrin J","year":2025,"journal":"Nature, 641(8061), 192-201","doi":"10.1038/s41586-025-08683-y","pmid":"40044869","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10513","title":"Porphyromonas gingivalis outer membrane vesicles divert host innate immunity and promote inflammation via C4' monophosphorylated lipid A.","authors":"Coats, Stephen R; Su, Thet Hnin; Luderman Miller, Zoe; King, Alisa J; Ortiz, Joshua; Reddy, Angel; Alaei, Sarah R; Jain, Sumita","year":2025,"journal":"Journal of immunology (Baltimore, Md. : 1950), 214(5), 1008-1021","doi":"10.1093/jimmun/vkae050","pmid":"40131356","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"P. gingivalis maintains an immunoevasive outer membrane containing nonphosphorylated lipid A (NPLA), which evades TLR4 detection, inflammasome activation, and LL-37 antimicrobial peptide killing. Simultaneously, it releases outer membrane vesicles (OMVs) enriched with C4'-monophosphoryl lipid A (C4'-MPLA) — a potent TLR4 agonist.\n\nThese OMVs serve as proinflammatory decoys: they engage and redirect TLR4 signaling, inflammasome activation, and LL-37 binding away from the bacterium. Both polymyxin B and the host defense peptide LL-37 blocked OMV-stimulated TLR4 activation in multiple cell types (HEK cells, THP-1 monocytes, endothelial cells). A mutant bacterium lacking the ability to dephosphorylate its membrane lipid A (ΔlpxF) retained C4'-MPLA on its surface and was killed by LL-37, confirming that lipid A modification is the key to immune evasion. Pg 381, which produced more OMVs, showed higher proinflammatory pathogenicity.","whyItMatters":"Periodontal disease affects nearly half of adults and is increasingly linked to systemic conditions including atherosclerosis, rheumatoid arthritis, and Alzheimer's disease. This study reveals a sophisticated mechanism by which P. gingivalis simultaneously avoids immune killing and drives chronic inflammation — explaining how this single bacterium can persist in the mouth for years while fueling disease throughout the body. Understanding how it diverts antimicrobial peptide defenses could lead to targeted therapies that break this cycle.","specificNumbers":"","methodology":"The researchers characterized lipid A structures in P. gingivalis outer membranes and released OMVs using biochemical analysis. TLR4 activation was measured in HEK-Blue cells, IL-1β production in THP-1 monocytes, and endothelial responses in human umbilical vein endothelial cells (HUVECs). Peptide inhibition assays used polymyxin B and LL-37 to block OMV-mediated signaling. Two P. gingivalis strains (381 and 33277) were compared for OMV production. A ΔlpxF mutant was used to confirm the role of lipid A dephosphorylation in LL-37 resistance.","limitations":"The study used cell-based models (HEK, THP-1, HUVECs) rather than in vivo animal or human studies, so the relevance of OMV-mediated decoy effects in the complex oral environment is uncertain. Only two P. gingivalis strains were compared. The study demonstrates correlation between OMV production and pathogenicity but doesn't directly prove the decoy mechanism drives disease outcomes in patients. The contribution of OMV-C4'-MPLA to specific comorbidities (atherosclerosis, Alzheimer's) remains speculative based on the cytokine profiles observed."},{"rthcId":"RPEP-10514","title":"GLP-1 agonists and exercise: the future of lifestyle prioritization.","authors":"Codella, Roberto; Senesi, Pamela; Luzi, Livio","year":2025,"journal":"Frontiers in clinical diabetes and healthcare, 6, 1720794","doi":"10.3389/fcdhc.2025.1720794","pmid":"41367404","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review synthesizes several key findings from recent literature:\n\n1. GLP-1 receptor agonists often surpass lifestyle interventions alone for weight loss and metabolic/cardiovascular improvements\n2. Stopping GLP-1 therapy frequently leads to weight regain when lifestyle changes haven't been established\n3. Exercise helps preserve muscle mass during GLP-1-mediated weight loss, which is critical because muscle loss reduces metabolic rate and functional capacity\n4. Combining GLP-1 agonists with strength training and increased protein intake mitigates the muscle loss problem\n5. Long-term weight maintenance is more successful when exercise is part of the treatment plan\n6. Future obesity management will likely prioritize integrated pharmacotherapy + lifestyle approaches rather than medication alone","whyItMatters":"Millions of people are now taking GLP-1 drugs, but the conversation has largely been about the drugs themselves rather than what should accompany them. The muscle loss problem is real — studies show 30-40% of weight lost on GLP-1 drugs can be lean mass (muscle) rather than fat. Since muscle is metabolically active and essential for mobility, losing it makes long-term weight maintenance harder and can impair quality of life, especially in older adults. This review makes the case that prescribing exercise alongside GLP-1 drugs should be standard practice.","specificNumbers":"","methodology":"This is a narrative review synthesizing recent literature on the interaction between GLP-1 receptor agonist therapy and exercise/lifestyle interventions for obesity management.","limitations":"As a narrative review, this does not present original data or systematic methodology. The specific degree of muscle preservation from exercise during GLP-1 therapy is not quantified. The optimal exercise prescription (type, frequency, intensity, duration) for maximizing GLP-1 agonist outcomes is not fully defined. Adherence to exercise programs is a well-known challenge, and the review does not address strategies for improving long-term exercise compliance. The review focuses on exercise and does not detail other lifestyle factors like sleep, stress, or behavioral therapy."},{"rthcId":"RPEP-10515","title":"T-cell receptor sequencing for detection of Epstein-Barr and cytomegalovirus-specific immune responses in glioma patients: An exploratory study.","authors":"Coghill, Anna E; Van Bibber, Nathan; Yoder, Sean; Mokhtari, Sepideh; Forsyth, Sugriva; Blanck, George; Egan, Kathleen M","year":2025,"journal":"Neuro-oncology advances, 7(1), vdaf216","doi":"10.1093/noajnl/vdaf216","pmid":"41624423","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10516","title":"Impact of changes in conventional risk factors induced by once-weekly GLP-1 receptor agonist exenatide on cardiovascular outcomes: an EXSCEL post hoc analysis.","authors":"Coleman, Ruth L; Adler, Amanda I; Mentz, Robert J; Fudim, Marat; Sattar, Naveed; Holman, Rury R","year":2025,"journal":"Cardiovascular diabetology, 24(1), 347","doi":"10.1186/s12933-025-02866-7","pmid":"40849664","tags":["glp-1-agonists","cardiovascular-health","diabetes"],"studyType":"human-rct","evidenceStrength":"strong","keyFinding":"Using a validated diabetes outcomes model and participant-level data from EXSCEL, the researchers simulated how much of exenatide's cardiovascular benefits should result from its improvements in HbA1c, blood pressure, heart rate, LDL cholesterol, triglycerides, and weight.\n\nThe model could only explain modest proportions of the observed benefits: 29% for MACE (major adverse cardiovascular events), 15% for all-cause mortality, 18% for cardiovascular death, and 29% for stroke. The model explained more for hospitalization for heart failure (67%) and myocardial infarction (200% — meaning risk factors predicted more benefit than was actually observed for MI). Mediation analysis confirmed that changes in these conventional risk factors up to 12 months did not mediate the reduction in all-cause mortality.","whyItMatters":"This analysis addresses one of the biggest questions in GLP-1 pharmacology: how do these drugs reduce cardiovascular events and death? If the benefits came mainly from improving blood sugar and cholesterol, then any drug achieving those improvements should have similar heart benefits. But the finding that 70-85% of the cardiovascular benefit is unexplained by traditional risk factors suggests GLP-1 drugs have direct cardioprotective effects — potentially through anti-inflammatory pathways, improved endothelial function, or direct cardiac effects. This changes how we think about prescribing these drugs and who should receive them.","specificNumbers":"MACE reduction: 29% explained · ACM: 15% explained · CV death: 18% explained · Stroke: 29% explained · hHF: 67% explained · MI: 200% explained · Risk factors did not mediate ACM reduction","methodology":"This was a post hoc analysis of the EXSCEL trial (Exenatide Study of Cardiovascular Event Lowering), which randomized patients with type 2 diabetes to once-weekly exenatide or placebo. The researchers entered individual participant risk factor values over time into a validated type 2 diabetes clinical outcomes model to estimate expected cardiovascular event rates based on observed risk factor changes. They then compared these model-predicted outcomes with the actual trial results across six endpoints. They also performed mediation analysis using Cox regression to evaluate whether specific risk factor changes mediated the effect on all-cause mortality.","limitations":"This is a post hoc analysis, meaning these questions were explored after the trial was completed rather than being pre-specified. The validated outcomes model, while well-established, may not capture all pathways through which risk factor changes affect outcomes. Risk factor changes were measured only up to 12 months, so longer-term effects may differ. The analysis cannot identify what the unexplained mechanisms actually are — it can only show that traditional risk factors don't account for the full benefit."},{"rthcId":"RPEP-10517","title":"Unanticipated Adverse Events With Tirzepatide: Three Cases Underscoring the Importance of Postmarketing Monitoring.","authors":"Colorado, Maria; Gomez Miranda, Jose; Arias-Morales, Carlos E","year":2025,"journal":"JCEM case reports, 3(10), luaf195","doi":"10.1210/jcemcr/luaf195","pmid":"40895495","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10518","title":"Permeation enhancer-induced membrane defects assist the oral absorption of peptide drugs.","authors":"Colston, Kyle J; Faivre, Kyle T; Schneebeli, Severin T","year":2025,"journal":"Nature communications, 16(1), 9512","doi":"10.1038/s41467-025-64891-0","pmid":"41152279","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10519","title":"Glucagon-like peptide-1 (GLP-1) receptor agonists in inflammatory bowel disease: mechanisms, clinical implications, and therapeutic potential.","authors":"Colwill, Michael; Povlsen, Sebastian; Pollok, Richard; Patel, Kamal; Goodhand, James; Ahmad, Tariq; Honap, Sailish","year":2025,"journal":"Journal of Crohn's & colitis, 19(9)","doi":"10.1093/ecco-jcc/jjaf167","pmid":"40972535","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10520","title":"Legal Challenges to Compounding Drugs for Weight Loss.","authors":"Combs, Blinn E; Howard, Brad","year":2025,"journal":"International journal of pharmaceutical compounding, 29(4), 267-278","doi":null,"pmid":"40961473","tags":["glp-1-agonists","regulation"],"studyType":"review","evidenceStrength":"expert-opinion","keyFinding":"Compounding pharmacies and outsourcing facilities face significant legal risks from producing compounded semaglutide and tirzepatide. While drug shortages and lack of insurance coverage for weight-loss use created strong financial incentives, the regulatory framework creates substantial liability.\n\nThe review identifies multiple risk areas: FDA enforcement against compounders, patent and trademark infringement claims from brand manufacturers, state-level regulatory actions, and potential liability from adverse patient outcomes. The fact that weight loss prescribing typically falls outside federal healthcare programs reduces some kickback risks but doesn't eliminate the core compounding legality questions.","whyItMatters":"Compounded semaglutide became a multi-billion-dollar grey market practically overnight. Millions of patients turned to compounding pharmacies when branded Ozempic and Wegovy were in chronic shortage and insurance wouldn't cover weight-loss prescriptions. This review lays out the legal minefield that both compounders and prescribing physicians face — a reality check for an industry that grew faster than the regulatory framework could keep up.","specificNumbers":"Focus period: ~3 years of explosive growth in compounded GLP-1 market · primarily semaglutide and tirzepatide · weight loss use typically not covered by insurance · legal risks span federal, state, and civil litigation domains","methodology":"Legal review article examining the regulatory framework for compounding semaglutide and tirzepatide, including FDA regulations, patent law, state pharmacy board rules, and relevant case law. The authors review the history of compounding regulation and apply it to the specific context of GLP-1 weight loss drugs.","limitations":"This is a legal commentary, not empirical research — it describes risks and regulatory frameworks rather than measuring outcomes. The legal landscape is evolving rapidly and varies by jurisdiction. The article focuses primarily on semaglutide with broader applicability noted for tirzepatide. It provides a cursory overview, as the authors note, not comprehensive legal guidance."},{"rthcId":"RPEP-10521","title":"12-month outcomes of GLP - 1 in severe pediatric obesity: real-world data.","authors":"Cominato, Louise; Resende, Mariana L; Bernardes, Natalia; Rachid, Ludmila L; Passone, Caroline G B; Mattar, Larissa B F; Neme, Georgia; Souza, Sarah G; Santos, Claudia Renata P; Franco, Ruth R; Damiani, Durval","year":2025,"journal":"Frontiers in endocrinology, 16, 1663499","doi":"10.3389/fendo.2025.1663499","pmid":"41048426","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10522","title":"Exposure Matching Using Population Pharmacokinetic Modeling and Simulation to Support Rimegepant Dose Selection for Pediatric Patients With Migraine.","authors":"Comisar, Craig M; Hughes, Jim H; Mo, Gary; Bhardwaj, Rajinder; Jakate, Abhijeet; Lim, Chay Ngee; Liu, Jing","year":2025,"journal":"Clinical and translational science, 18(10), e70360","doi":"10.1111/cts.70360","pmid":"41105969","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10523","title":"Population Pharmacokinetic Modeling of the Oral Calcitonin Gene-Related Peptide Receptor Antagonist Rimegepant in Adults.","authors":"Comisar, Craig M; Hughes, Jim H; Francis, Jose; Chinda, Yorinao; Sano, Yamato; Muto, Chieko; Neumar, Christine; Bhardwaj, Rajinder; Bertz, Richard; Liu, Jing","year":2025,"journal":"CPT: pharmacometrics & systems pharmacology, 14(8), 1332-1345","doi":"10.1002/psp4.70051","pmid":"40614133","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10524","title":"Population pharmacokinetic modeling of zavegepant, a calcitonin gene-related peptide receptor antagonist, in healthy adults and patients with migraine.","authors":"Comisar, Craig M; Francis, Jose; Hughes, Jim H; Bhardwaj, Rajinder; Bertz, Richard; Liu, Jing","year":2025,"journal":"CPT: pharmacometrics & systems pharmacology, 14(1), 179-191","doi":"10.1002/psp4.13257","pmid":"39492601","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10525","title":"Unleashing IbKTP-NH2, a kyotorphin derivative, against bacterial and fungal multispecies biofilm adhesion and viability on materials.","authors":"Conceição, Katia; de Andrade, Vitor M; de Oliveira, Vitor D M; Ramu, Vasanthakumar G; Heras, Montserrat; Bardaji, Eduard R; Castanho, Miguel A R B; Capella, Aline G","year":2025,"journal":"Journal of applied microbiology, 136(9)","doi":"10.1093/jambio/lxaf205","pmid":"40802474","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"IbKTP-NH2 was tested against multispecies biofilms containing C. albicans, P. aeruginosa, and S. pneumoniae on polymeric and metallic medical device materials:\n\n- Minimum biofilm inhibitory concentrations (MBIC) ranged from 46.5 to 1 mM for bacterial strains\n- SEM analysis showed significant biofilm disruption: reduced extracellular matrix production, decreased cell density, and altered cell morphology\n- Effective on both polymeric and metallic surfaces relevant to medical devices\n- Demonstrated potential antivirulence properties beyond direct antimicrobial killing\n\nThe peptide's dual origin — combining a neuropeptide (kyotorphin) with an anti-inflammatory (ibuprofen) — provides both antimicrobial and potentially anti-inflammatory activity.","whyItMatters":"Healthcare-associated infections from biofilms on medical devices cause significant illness and death worldwide. Multi-species biofilms are especially dangerous because they're more resistant than single-species infections. A peptide-based approach that can disrupt these complex communities on device surfaces could prevent infections before they start.","specificNumbers":"","methodology":"Multispecies biofilms of C. albicans, P. aeruginosa, and S. pneumoniae were cultured on polymeric and metallic materials mimicking medical device surfaces. Antimicrobial susceptibility testing determined minimum biofilm inhibitory concentrations (MBIC). Scanning electron microscopy (SEM) analyzed biofilm architecture including extracellular matrix, cell density, and morphology after treatment.","limitations":"The MBIC values (up to 46.5 mM) are relatively high, which may limit clinical applicability due to required concentrations. Testing was in vitro only — no animal or human studies were conducted. Long-term stability of the peptide on device surfaces was not assessed. The specificity of action and potential for cytotoxicity to human cells were not reported in the abstract."},{"rthcId":"RPEP-10526","title":"Efficacy and safety of anti-obesity drugs in metabolic dysfunction-associated steatotic liver disease: An updated review.","authors":"Concepción-Zavaleta, Marcio J; Fuentes-Mendoza, Jenyfer M; Gonzáles-Yovera, Jhean G; Ruvalcaba-Barbosa, Gemma Y; Cura-Rodríguez, Leonardo D; González-Rodríguez, Josué S; Concepción-Urteaga, Luis A; Pérez-Reyes, Aranza I; Quiroz-Aldave, Juan Eduardo; Paz-Ibarra, José","year":2025,"journal":"World journal of gastroenterology, 31(37), 111435","doi":"10.3748/wjg.v31.i37.111435","pmid":"41025003","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10527","title":"Type 2 Diabetes in a 4-Year-Old With Obesity: Considerations for Use of Semaglutide and Bariatric Surgery in Children.","authors":"Connard, James; Simonian, Armine; Monzavi, Roshanak; Samakar, Kamran; Vidmar, Alaina P","year":2025,"journal":"JCEM case reports, 3(9), luaf142","doi":"10.1210/jcemcr/luaf142","pmid":"40689302","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10528","title":"Cathelicidin expression in the pathogenesis of atopic dermatitis and the therapeutic potential of vitamin D.","authors":"Connell, Tess; Seidler, Karin; Neil, James","year":2025,"journal":"Nutrition research (New York, N.Y.), 139, 113-123","doi":"10.1016/j.nutres.2025.05.006","pmid":"40517664","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The systematic review of 68 peer-reviewed papers established two key findings:\n\n1. Cathelicidin plays a dual role in atopic dermatitis — it contributes to skin barrier function and has direct anti-Staphylococcus aureus activity. Reduced cathelicidin expression in AD patients weakens both defenses.\n\n2. Vitamin D supplementation at 1,000-2,000 IU/day for 1-3 months increases cathelicidin expression and reduces S. aureus abundance and AD severity — but only in individuals with low serum vitamin D (deficiency/insufficiency). There was no evidence supporting supplementation in people with sufficient vitamin D levels.","whyItMatters":"Atopic dermatitis affects up to 20% of children and 10% of adults, and S. aureus skin infections are a major complication causing disease flares. Current treatment relies on topical steroids and immunosuppressants, which have side effects with long-term use. The cathelicidin-vitamin D connection offers a natural, low-cost intervention: simply correcting vitamin D deficiency can boost the body's own antimicrobial peptide defense, reducing infections and eczema severity. This represents a mechanistic, nutrition-based approach to managing a common chronic condition.","specificNumbers":"","methodology":"Systematic literature search following established protocols, with 68 peer-reviewed papers accepted for inclusion. Studies were critically appraised and synthesized in a narrative analysis. The review examined three interconnected relationships: cathelicidin's role in skin barrier function, cathelicidin's anti-S. aureus activity, and vitamin D's ability to upregulate cathelicidin expression in the context of atopic dermatitis.","limitations":"The review is a narrative synthesis rather than a formal meta-analysis, limiting quantitative conclusions. Most vitamin D supplementation studies in AD are small and heterogeneous in design. The benefit is limited to vitamin D-deficient/insufficient individuals, and many studies didn't stratify by baseline vitamin D status. Optimal dosing and duration beyond the identified 1,000-2,000 IU/day for 1-3 months range are not established. The causal chain (low VD → low cathelicidin → worse AD) is well-supported mechanistically but not definitively proven in clinical trials."},{"rthcId":"RPEP-10529","title":"Glucagon-Like Peptide 1 Receptor Agonists and Chronic Lower Respiratory Disease Among Type 2 Diabetes Patients: Replication and Reliability Assessment Across a Research Network.","authors":"Conover, Mitchell M; Albogami, Yasser; Hardin, Jill; Reich, Christian G; Ostropolets, Anna; Ryan, Patrick B","year":2025,"journal":"Pharmacoepidemiology and drug safety, 34(1), e70087","doi":"10.1002/pds.70087","pmid":"39805811","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10530","title":"The Impact of Glucagon-Like Peptide-1 Receptor Agonists on Fracture Risk in Overweight or Obese, Nondiabetic Patients.","authors":"Constantine, Evangelia; Enthoven, Luke; Kahan, Riley; Pflug, Emily M; Lauder, Alexander","year":2025,"journal":"The Journal of the American Academy of Orthopaedic Surgeons","doi":"10.5435/JAAOS-D-24-01505","pmid":"41429015","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10531","title":"B-type natriuretic peptide in Parkinson's disease: a novel biomarker of dysautonomia.","authors":"Contaldi, Elena; Corradi, Marta; Percetti, Marco; Pilleri, Manuela; Calandrella, Daniela; Isaias, Ioannis U; Pezzoli, Gianni; Del Sorbo, Francesca","year":2025,"journal":"Parkinsonism & related disorders, 141, 108079","doi":"10.1016/j.parkreldis.2025.108079","pmid":"41124961","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"NT-proBNP levels were significantly elevated in Parkinson's disease patients with neurogenic orthostatic hypotension (adjusted P = 0.001) and in those with pathologically absent overshoot during the Valsalva Maneuver (adjusted P = 0.001). The peptide marker also correlated significantly with changes in systolic and diastolic blood pressure during the Head-up Tilt Test (P = 0.011 and P = 0.027, respectively) and with the blood pressure response in Valsalva phase III (P = 0.024).\n\nROC curve analysis revealed that NT-proBNP had high discriminatory power for detecting dysautonomia in Parkinson's patients, achieving an area under the curve of 0.917 (P < 0.0001). NT-proBNP levels also correlated with patients' self-reported cardiovascular symptoms.","whyItMatters":"Cardiovascular autonomic dysfunction is common in Parkinson's disease but currently requires specialized, time-consuming autonomic function testing to detect. If NT-proBNP — a simple, widely available blood test — can reliably flag this dysfunction, it could enable earlier identification of at-risk patients and potentially guide treatment decisions for managing orthostatic hypotension and related symptoms.","specificNumbers":"","methodology":"The researchers enrolled 31 consecutive Parkinson's disease patients and measured their NT-proBNP blood levels. Each patient underwent a battery of cardiovascular autonomic function tests, including the Head-up Tilt Test for orthostatic blood pressure changes, the Valsalva Maneuver for baroreceptor function, the Hand Grip test, and the Deep Breathing test for heart rate variability. They used ROC curve analysis to assess how well NT-proBNP could distinguish patients with dysautonomia, and multivariable linear regression to identify independent associations.","limitations":"The study included only 31 patients, which is a small sample size that limits the generalizability of the findings. As a single-center study, the results need validation in larger, more diverse populations. The cross-sectional design means it cannot establish whether elevated NT-proBNP precedes dysautonomia or simply accompanies it. Additionally, patients with known heart failure were likely excluded, so the marker's specificity in patients with concurrent cardiac disease remains unclear."},{"rthcId":"RPEP-10532","title":"Comparing medication persistence with oral and subcutaneous semaglutide in a real-world setting.","authors":"Conti, Matteo; Pontiggia, Lorenzo; Vergani, Michela; Muraca, Emanuele; Cannistraci, Rosa; Perra, Silvia; Lattuada, Guido; Perseghin, Gianluca; Ciardullo, Stefano","year":2025,"journal":"Acta diabetologica, 62(7), 1065-1072","doi":"10.1007/s00592-024-02424-9","pmid":"39680131","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10533","title":"One-month atogepant treatment induces rapid changes in delta-band functional connectivity in migraine: an HD-EEG study.","authors":"Conti, Matteo; Bagetta, Silvio; Carparelli, Federico; Ferrari, Valerio; D'Agostino, Vittoria Carla; Placidi, Fabio; Stefani, Alessandro; Mercuri, Nicola Biagio; Albanese, Maria","year":2025,"journal":"The journal of headache and pain, 26(1), 171","doi":"10.1186/s10194-025-02115-y","pmid":"40739615","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10534","title":"De novo expression of neuropeptide Y in sensory neurons does not contribute to peripheral neuropathic pain.","authors":"Cooper, A H; Nie, A A; Hedden, N S; Herzog, H; Taylor, B K","year":2025,"journal":"The journal of pain, 30, 105385","doi":"10.1016/j.jpain.2025.105385","pmid":"40174733","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10535","title":"De novo expression of neuropeptide Y in sensory neurons does not contribute to peripheral neuropathic pain.","authors":"Cooper, A H; Nie, A; Hedden, N S; Herzog, H; Taylor, B K","year":2025,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2025.01.25.634591","pmid":"39975116","tags":[],"studyType":"animal study","evidenceStrength":"low","keyFinding":"Nerve injury causes sensory neurons to start producing neuropeptide Y (NPY) — a pain-modulating peptide — for the first time. Researchers genetically deleted NPY specifically from sensory neurons in mice to test whether this newly produced NPY contributes to neuropathic pain. Surprisingly, removing NPY from sensory neurons had no effect on mechanical pain, cold pain, or ongoing pain in two different nerve injury models. The study found that NPY's pain-inhibiting role in the spinal cord is actually mediated by spinal cord interneurons releasing NPY, not by the sensory neurons themselves. This overturns a long-held assumption about the source of pain-modulating NPY after nerve injury.","whyItMatters":"Understanding where pain-modulating peptides come from in the nervous system is critical for developing targeted pain therapies. For years, the dramatic upregulation of NPY in sensory neurons after nerve injury was assumed to be functionally important for neuropathic pain. This study shows that assumption was wrong — the pain-relevant NPY comes from spinal cord interneurons instead. This redirects therapeutic targeting efforts toward the spinal cord rather than peripheral sensory neurons for NPY-based pain treatments.","specificNumbers":"2 nerve injury models (SNI, tSNI) · NPY Y1 receptor antagonist BIBO3304 used · Conditional knockout in DRG sensory neurons","methodology":"Researchers created conditional knockout mice (Pirt-NPY) that lacked the NPY gene specifically in dorsal root ganglion sensory neurons while maintaining normal NPY expression in the brain and spinal cord interneurons. They tested these mice and wild-type controls in two nerve injury models (spared sural nerve injury and spared tibial nerve injury), measuring static mechanical allodynia, dynamic mechanical allodynia, cold allodynia, and ongoing pain using conditioned place preference to gabapentin. They also tested whether the NPY Y1 receptor antagonist BIBO3304 could reinstate pain sensitivity after recovery.","limitations":"This is a mouse study, and the relevance of these findings to human neuropathic pain is uncertain. The conditional knockout approach, while elegant, may have incomplete deletion efficiency. The study focused on specific nerve injury models that may not represent all forms of neuropathic pain. As a bioRxiv preprint, these findings have not yet undergone peer review."},{"rthcId":"RPEP-10536","title":"GLP-1 agonists in the treatment of chronic kidney disease in type 2 diabetes and obesity.","authors":"Cooper, Mark E; van Raalte, Daniël H","year":2025,"journal":"The Journal of clinical investigation, 135(21)","doi":"10.1172/JCI194749","pmid":"41178712","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10537","title":"The inhibitor VB-87531 synergizes with tirzepatide and semaglutide for greater weight loss in DIO mice.","authors":"Corbalan, J Jose; Petronella, Brenda A; Huang, Chia-Yu; Beasley, James R; Merritt, James R; Mugrage, Benjamin B; Nickels, Joseph T","year":2025,"journal":"Biochemical and biophysical research communications, 778, 152360","doi":"10.1016/j.bbrc.2025.152360","pmid":"40694906","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"VB-87531 is a potent inhibitor of human MOGAT2 (IC50 = 17.4 nM) that, when administered to diet-induced obese mice:\n\nAlone: reduced body weight, food intake, blood cholesterol, and glucose levels with no liver toxicity\n\nCombined with tirzepatide: enhanced weight loss and reduced food intake vs. VB-87531 alone; dose-dependent modulation of both outcomes\n\nCombined with semaglutide: similarly enhanced weight loss and reduced food intake vs. VB-87531 alone\n\nBoth combinations significantly lowered insulin and leptin levels while increasing FGF21 (a metabolic hormone linked to fat burning) and PYY (a satiety peptide). The synergistic effects suggest complementary mechanisms: VB-87531 blocks dietary fat absorption while GLP-1/GIP agonists suppress appetite and improve metabolic signaling.","whyItMatters":"Despite the remarkable success of GLP-1 drugs, many patients don't lose enough weight to resolve their obesity-related health problems. Finding drugs that synergize with existing peptide therapies could push weight loss to levels approaching bariatric surgery without the need for an operation. Targeting fat absorption (MOGAT2) complements the appetite suppression of GLP-1 drugs — attacking obesity from two different angles simultaneously.","specificNumbers":"","methodology":"Diet-induced obese (DIO) mice fed a high-fat diet were treated with VB-87531 alone, tirzepatide alone, semaglutide alone, or combinations of VB-87531 with either peptide drug. Outcomes included body weight changes, food intake, blood cholesterol, glucose, insulin, leptin, FGF21, and PYY levels. Liver toxicity was assessed. Dose-dependent effects were evaluated for the VB-87531/tirzepatide combination.","limitations":"This is a mouse study using diet-induced obesity, which may not fully predict human responses. The specific degree of additional weight loss from combination therapy vs. monotherapy is not quantified in the abstract. VB-87531 has not been tested in humans (unlike the related compound BMS-963272). Long-term safety of blocking fat absorption chronically is unknown — potential concerns include fat-soluble vitamin deficiency and gastrointestinal side effects. The dose-dependency was only assessed with tirzepatide, not semaglutide."},{"rthcId":"RPEP-10538","title":"Cardiovascular outcomes and mortality of bariatric surgery versus glucagon-like peptide-1 receptor agonists: a systematic review and meta-analysis.","authors":"Cordova, Felipe; Málaga, Néstor","year":2025,"journal":"Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery","doi":"10.1016/j.soard.2025.11.024","pmid":"41506923","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10539","title":"Novel Insights on the Synergistic Mechanism of Action Between the Polycationic Peptide Colistin and Cannabidiol Against Gram-Negative Bacteria.","authors":"Corleto, Merlina; Garavaglia, Matías; Martínez, Melina M B; Weschenfeller, Melanie; Montes, Santiago Urrea; Aran, Martin; Pellizza, Leonardo; Faccone, Diego; Maffía, Paulo C","year":2025,"journal":"Pharmaceutics, 18(1)","doi":"10.3390/pharmaceutics18010051","pmid":"41599157","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10540","title":"Epigenetic Aging and Treatment Response to Semaglutide in the SLIM LIVER Study.","authors":"Corley, Michael; Pang, Alina; Kitch, Douglas; Kantor, Amy; Sattler, Fred; Belaunzaran-Zamudio, Pablo; Brown, Todd; Landay, Alan; Lake, Jordan; Erlandson, Kristine","year":2025,"journal":"Research square","doi":"10.21203/rs.3.rs-7697256/v1","pmid":"41256006","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10541","title":"CROI 2025: neuropsychiatric complications in people with HIV.","authors":"Corley, Michael J; Chan, Phillip; Joseph, Sarah B","year":2025,"journal":"Topics in antiviral medicine, 33(2), 483-493","doi":null,"pmid":"40472384","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10542","title":"Semaglutide Slows Epigenetic Aging in People with HIV-associated lipohypertrophy: Evidence from a Randomized Controlled Trial.","authors":"Corley, Michael J; Dwaraka, Varun; Pang, Alina Ps; Labbato, Danielle; Smith, Ryan; Eckard, Allison Ross; McComsey, Grace A","year":2025,"journal":"medRxiv : the preprint server for health sciences","doi":"10.1101/2025.07.09.25331038","pmid":"40791720","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In a post-hoc analysis of a 32-week, double-blind, placebo-controlled trial (semaglutide n=45, placebo n=39), semaglutide significantly decreased multiple epigenetic aging measures after adjustment for sex, BMI, hsCRP, and sCD163:\n\n- PCGrimAge: -3.1 years (p=0.007)\n- GrimAge V1: -1.4 years (p=0.02)\n- GrimAge V2: -2.3 years (p=0.009)\n- PhenoAge: -4.9 years (p=0.004)\n- DunedinPACE: -0.09 units, approximately 9% slower pace of aging (p=0.01)\n- OMICmAge: -2.2 years (p=0.009)\n- RetroAge: -2.2 years (p=0.030)\n\nEleven organ-system clocks showed concordant decreases with semaglutide, most prominently in inflammation, brain, and heart clocks. An Intrinsic Capacity epigenetic clock was unchanged.","whyItMatters":"GLP-1 receptor agonists like semaglutide have been proposed as potential anti-aging drugs, but until now there was no clinical trial evidence supporting this. This study provides the first randomized, controlled evidence that semaglutide modulates validated epigenetic biomarkers of aging. If confirmed in broader populations, it could reframe GLP-1 drugs not just as diabetes/obesity treatments but as potential healthspan-extending therapies.","specificNumbers":"","methodology":"Post-hoc epigenetic analysis of a 32-week, double-blind, placebo-controlled Phase 2b clinical trial in adults with HIV-associated lipohypertrophy. Paired peripheral blood DNA methylation profiles were measured before and after treatment. Multiple generations of validated DNA methylation aging clocks were applied, and results were adjusted for sex, BMI, high-sensitivity CRP, and sCD163.","limitations":"This was a post-hoc analysis, not a pre-specified endpoint of the original trial. The study population (people with HIV-associated lipohypertrophy) may have accelerated aging at baseline, so results may not generalize to healthy populations. The sample size was small (84 total). The trial was only 32 weeks, so durability of effects is unknown. Epigenetic clock changes are biomarker surrogates — it remains unproven whether they translate to actual healthspan extension. The study was published as a preprint (medRxiv) and has not yet been peer-reviewed."},{"rthcId":"RPEP-10543","title":"Cardiac alterations induced by Trypanosoma cruzi extracellular vesicles and immune complexes.","authors":"Cornet-Gomez, Alberto; O'Valle, Francisco; Garrido, José M; Serrano, Fernando Rodríguez; Nieto, Ana I; Osuna, Antonio","year":2025,"journal":"PLoS neglected tropical diseases, 19(7), e0013273","doi":"10.1371/journal.pntd.0013273","pmid":"40623042","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10544","title":"Type 2 Diabetes Mellitus Remission, Dream or Reality? A Narrative Review of Current Evidence and Integrated Care Strategies.","authors":"Corrao, Salvatore; Falcone, Fabio; Mirarchi, Luigi; Amodeo, Simona; Calvo, Luigi","year":2025,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 16(8), 1557-1579","doi":"10.1007/s13300-025-01761-4","pmid":"40512404","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10545","title":"Weight Management in a Patient With Smith-Magenis Syndrome: The Role of GLP-1 Receptor Agonists.","authors":"Correia, Jorge César; Frayling, Timothy; Pataky, Zoltan","year":2025,"journal":"JCEM case reports, 3(7), luaf094","doi":"10.1210/jcemcr/luaf094","pmid":"40443456","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10546","title":"Modulation of temporoammonic-CA1 synapses by neuropeptide Y is through Y1 receptors in mice.","authors":"Cortes, Mariana A; Bartley, Aundrea F; Li, Qin; Davis, Taylor R; Cunningham, Stephen E; Garner, Mary Anne; Perez, Patric J; Harvey, Adela C; Gross, Alecia K; Dobrunz, Lynn E","year":2025,"journal":"Neuropeptides, 110, 102504","doi":"10.1016/j.npep.2025.102504","pmid":"39951960","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10547","title":"Innovative therapeutics for renoprotection: Where we are.","authors":"Cortinovis, Monica; Perico, Norberto; Remuzzi, Giuseppe","year":2025,"journal":"Pharmacological reviews, 77(4), 100060","doi":"10.1016/j.pharmr.2025.100060","pmid":"40382796","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10548","title":"Cardiovascular Protection in Coronary Artery Disease: Mechanistic and Clinical Insights into SGLT2 Inhibitors and GLP-1 Receptor Agonists.","authors":"Cosentino, Nicola; Trombara, Filippo; De Metrio, Monica; Molinari, Chiara; Genovese, Stefano; Pontone, Gianluca; Marenzi, Giancarlo","year":2025,"journal":"Pharmaceuticals (Basel, Switzerland), 18(8)","doi":"10.3390/ph18081202","pmid":"40872593","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10549","title":"Effects of retatrutide on body composition in people with type 2 diabetes: a substudy of a phase 2, double-blind, parallel-group, placebo-controlled, randomised trial.","authors":"Coskun, Tamer; Wu, Qiwei; Schloot, Nanette C; Haupt, Axel; Milicevic, Zvonko; Khouli, Courtney; Harris, Charles","year":2025,"journal":"The lancet. Diabetes & endocrinology, 13(8), 674-684","doi":"10.1016/S2213-8587(25)00092-0","pmid":"40609566","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Fat mass reduction from baseline at 36 weeks was dose-dependent: 4.9% with retatrutide 0.5 mg, 15.2% with 4 mg, 26.1% with 8 mg, and 23.2% with 12 mg, compared to 4.5% for placebo and 2.6% for dulaglutide. Versus placebo, the 8 mg dose achieved a 21.6 percentage point greater fat reduction (p<0.0001). The 12 mg dose showed slightly less fat loss than 8 mg, though both were highly significant versus placebo.\n\nImportantly, the proportion of lean mass loss relative to total weight loss was comparable to other obesity treatments, providing reassurance that retatrutide's superior weight loss doesn't come with disproportionate muscle loss. Adverse events were mainly gastrointestinal and similar across groups.","whyItMatters":"A major concern with GLP-1-class weight loss drugs is that people lose muscle along with fat — so-called 'Ozempic butt' and sarcopenia concerns. This study shows that retatrutide, despite producing more dramatic fat loss than single-target GLP-1 drugs, doesn't cause proportionally more muscle loss. This is critical data because retatrutide adds glucagon receptor agonism (which may promote fat oxidation specifically) and could represent the next generation of obesity treatment.","specificNumbers":"","methodology":"Phase 2, double-blind, placebo-controlled, randomized substudy across 42 US medical centers. 189 adults with type 2 diabetes (BMI 25-50 kg/m²) were enrolled in the body composition substudy. Body composition was measured by dual-energy X-ray absorptiometry (DXA) at baseline and week 36. Participants received once-weekly subcutaneous injections of placebo, dulaglutide 1.5 mg, or retatrutide at various doses (0.5–12 mg). 103 participants completed both DXA scans.","limitations":"Only 103 participants completed both DXA scans out of 189 enrolled, representing significant attrition. The 36-week duration may not capture long-term body composition changes. The substudy was not powered as a primary endpoint study. The 12 mg dose showed less fat loss than 8 mg, which is unexpected and may reflect small sample sizes at individual dose levels. Funded by Eli Lilly (retatrutide's manufacturer)."},{"rthcId":"RPEP-10550","title":"Effects of the μ-opioid peptide and nociceptin/orphanin FQ peptide receptor agonist BU08028 on cocaine self-administration in male rhesus monkeys.","authors":"Costa, Marissa B; Collier, Miracle A; Epperly, Phillip M; Husbands, Stephen M; Cami-Kobeci, Gerta; Manzoor, Shoaib; Czoty, Paul W","year":2025,"journal":"The Journal of pharmacology and experimental therapeutics, 392(10), 103708","doi":"10.1016/j.jpet.2025.103708","pmid":"41037845","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10551","title":"Effectiveness and safety of daily oral semaglutide in people with type 2 diabetes mellitus switching from sulfonylureas: A real-world retrospective study.","authors":"Costa, Silvana; Miranda, Cesare; Elefante, Antonia; Vallone, Valeria; Vinci, Carmela; Borroni, Francesca; Brandoni, Gabriele; Labate, Antonio M; Lo Pomo, Feliciano; Strazzabosco, Marco","year":2025,"journal":"Diabetes, obesity & metabolism, 27(6), 3084-3093","doi":"10.1111/dom.16314","pmid":"40045764","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10552","title":"Advances in the management of obesity and heart failure: latest evidence from clinical trials.","authors":"Costa, Thomaz Alexandre; Harrington, Josephine L","year":2025,"journal":"Current opinion in cardiology, 40(3), 164-171","doi":"10.1097/HCO.0000000000001214","pmid":"39998461","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10553","title":"Machine learning-driven discovery of bioactive peptides from duckweed (Lemnaceae) protein hydrolysates: Identification and experimental validation of 20 novel antihypertensive, antidiabetic, and/or antioxidant peptides.","authors":"Cournoyer, Aurore; Bernier, Marie-Ève; Aboubacar, Hairati; de Toro-Martín, Juan; Vohl, Marie-Claude; Ravallec, Rozenn; Cudennec, Benoit; Bazinet, Laurent","year":2025,"journal":"Food chemistry, 482, 144029","doi":"10.1016/j.foodchem.2025.144029","pmid":"40209372","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10554","title":"The Real-World Use of Semaglutide to Promote Weight Loss in Obese Adults With Hemodialysis: A Multicenter Cross-Sectional Descriptive Study.","authors":"Couture, Jodianne; Robert, Pascale; Beauchesne, Marie-France; Dallaire, Gabriel; Lizotte, Annie; Lafrenière, Jo-Annie; Beauregard, Julie; Doucet, Janique","year":2025,"journal":"Canadian journal of kidney health and disease, 12, 20543581251324588","doi":"10.1177/20543581251324588","pmid":"40104387","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10555","title":"Prescription Drug Coverage of Guideline-Directed Medical Therapy for People Living with Heart Failure with Reduced Ejection Fraction in Canada.","authors":"Cowan, Simone S; Kosar, Lynette; Poon, Stephanie; Bains, Marc; Costigan, Jeannine; Ducharme, Anique; Gewarges, Mena; Groulx, Sharon; MacFarlane, Kendra; Nagpal, Seema; Singer, Alexander; McKelvie, Robert","year":2025,"journal":"CJC open, 7(10), 1271-1281","doi":"10.1016/j.cjco.2025.05.018","pmid":"41180344","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10556","title":"Association of tirzepatide with erectile dysfunction in people with type 2 diabetes.","authors":"Cowart, Kevin; Murphy, Christopher; Carris, Nicholas","year":2025,"journal":"Journal of diabetes and its complications, 39(10), 109116","doi":"10.1016/j.jdiacomp.2025.109116","pmid":"40614622","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10557","title":"Current treatment guidelines and glycated haemoglobin goals for type 2 diabetes: Which patients are most likely to benefit from fixed-ratio basal insulin glucagon-like peptide-1 receptor agonist combinations?","authors":"Cowart, Kevin; Carris, Nicholas W","year":2025,"journal":"Diabetes, obesity & metabolism, 27 Suppl 7(Suppl 7), 3-13","doi":"10.1111/dom.16502","pmid":"40497353","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10558","title":"Added Value to GLP-1 Receptor Agonist: Intermittent Fasting and Lifestyle Modification to Improve Therapeutic Effects and Outcomes.","authors":"Cozma, Dragos; Văcărescu, Cristina; Stoicescu, Claudiu","year":2025,"journal":"Biomedicines, 13(12)","doi":"10.3390/biomedicines13123079","pmid":"41463089","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10559","title":"Sensory and Autonomic Fibers in Anterior Ethmoid, Posterior Nasal, Posterolateral Nasal Nerves.","authors":"Craig, John R; Mason, William; Laumet, Geoffroy; Alkhoory, Wamidh; Hensley, Mark D; Holleman, Desiree; Hason, Noor","year":2025,"journal":"The Laryngoscope, 135(8), 2702-2712","doi":"10.1002/lary.32164","pmid":"40192001","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10560","title":"Substance P receptor signaling contributes to host maladaptive responses during enteric bacterial infection.","authors":"Cremin, Michael; Ramirez, Valerie T; Sanchez, Kristina; Tay, Emmy; Murray, Kaitlin; Brust-Mascher, Ingrid; Reardon, Colin","year":2025,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 122(7), e2415287122","doi":"10.1073/pnas.2415287122","pmid":"39937862","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10561","title":"GLP-1 Receptor Agonists and Gastrointestinal Endoscopy: A Narrative Review of Risks, Management Strategies, and the Need for Clinical Consensus.","authors":"Crespo, Javier; Rodríguez-Duque, Juan Carlos; Iruzubieta, Paula; Morel Cerda, Eliana C; Velarde-Ruiz Velasco, Jose Antonio","year":2025,"journal":"Journal of clinical medicine, 14(15)","doi":"10.3390/jcm14155597","pmid":"40807216","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10562","title":"Current and Emerging Roles of GLP1 Receptor Agonists Across the Spectrum of Left Ventricular Ejection Fraction in Heart Failure.","authors":"Crispino, Simone Pasquale; Nusca, Annunziata; Ferro, Aurora; Cricco, Riccardo; Ciancio, Martina; Segreti, Andrea; Cavallari, Ilaria; Sabatino, Mario; Potena, Luciano; Ussia, Gian Paolo; Grigioni, Francesco","year":2025,"journal":"Biomolecules, 15(11)","doi":"10.3390/biom15111574","pmid":"41301492","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide improved symptoms, functional capacity, and weight loss in HFpEF patients but did not reduce HF hospitalizations or mortality. Tirzepatide showed broader benefits, significantly reducing cardiovascular death and worsening HF events in obesity-related HFpEF. For HFrEF, clinical evidence supporting major outcome improvements is lacking, and concerns exist about increased HF hospitalizations, fluid retention, and arrhythmic risk. The review identifies a clear distinction between HFpEF (positive signal) and HFrEF (uncertain/cautious) for GLP-1 RA use.","whyItMatters":"Heart failure affects over 60 million people worldwide, and HFpEF — which accounts for about half of all cases — has had very few effective treatments. GLP-1 peptide drugs represent one of the first medication classes to show meaningful benefits in HFpEF, particularly for the large subgroup of patients whose heart failure is driven by obesity and metabolic disease. This could fundamentally change how HFpEF is treated.","specificNumbers":"","methodology":"Narrative review synthesizing evidence from recent randomized controlled trials (including STEP-HFpEF, SELECT, and SUMMIT), mechanistic studies, and existing guidelines to evaluate GLP-1 RA efficacy and safety across the full spectrum of heart failure by ejection fraction.","limitations":"The review is narrative rather than systematic. Key HFpEF trials excluded patients with very low ejection fractions, limiting extrapolation to HFrEF. The cardiovascular death reduction with tirzepatide was in obesity-related HFpEF specifically, and may not generalize to all HFpEF patients. Long-term safety in heart failure populations, particularly regarding fluid balance and arrhythmia risk, needs more data. The mechanisms behind GLP-1 RA benefits in HFpEF are not fully understood."},{"rthcId":"RPEP-10563","title":"Combined agonism of nutrient receptors GPR40 and GPR119 with K-757 and K-833 results in weight loss and blood pressure reductions in obese subjects without type 2 diabetes mellitus.","authors":"Crutchlow, Michael; Liu, Jiajun; Romero, Christopher; Watkins, Elaine; Zhang, Harry; Arreglado, Anna; Vance, Annemarie; Boisvert, Daniel; Terracina, Giuseppe; Chan, Bryan; Consolati, Matt J; Poterewicz, Gregory; Talaty, Jennifer E; Lauring, Brett","year":2025,"journal":"Diabetes, obesity & metabolism, 27(12), 7198-7209","doi":"10.1111/dom.70120","pmid":"40954563","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Co-administration of K-757 (GPR40 agonist) and K-833 (GPR119 agonist) in obese subjects produced dramatic increases in multiple gut peptide hormones: GLP-1 up 3.44x, active GLP-1 up 5.06x, PYY up 8.63x, GIP up 1.65x, CCK up 3.06x, and oxyntomodulin up 5.66x compared to placebo. In the 13-week Phase 2a trial (n=155), the combination produced placebo-adjusted weight loss of -2.78% (p<0.001) and blood pressure reductions of -6.9/-5.4 mmHg.\n\nK-757 alone also elevated gut peptides and produced blood pressure reductions (-5.3/-3.2 mmHg), though weight loss was more modest (-1.42%, p=0.076). GI adverse events were more common with active treatment.","whyItMatters":"Rather than injecting synthetic peptide hormones (like semaglutide or tirzepatide), this approach uses oral drugs to stimulate the body's own production of multiple satiety peptides simultaneously. The massive increases in GLP-1, PYY, oxyntomodulin, and CCK — all natural appetite-suppressing peptides — suggest a fundamentally different strategy for obesity treatment. The blood pressure reductions independent of weight loss hint at metabolic benefits that go beyond appetite suppression.","specificNumbers":"n=155 (Phase 2a) · 13 weeks · GLP-1 3.44x · Active GLP-1 5.06x · PYY 8.63x · GIP 1.65x · CCK 3.06x · Oxyntomodulin 5.66x · Weight loss -2.78% · BP -6.9/-5.4 mmHg","methodology":"Phase 1 study identified optimal dosing for maximal gut hormone secretion. Phase 2a was a randomized, double-blind, parallel-arm, 13-week study in 155 overweight-obese participants without type 2 diabetes, randomized to K-757 alone, K-757+K-833 combination, or placebo (~51-52/arm). Circulating gut peptide levels were measured. Primary outcomes included weight change; blood pressure was an exploratory endpoint.","limitations":"The 13-week Phase 2a study is relatively short, and the 2.78% weight loss, while significant, is modest compared to injectable GLP-1 agonists like semaglutide (~15%). GI adverse events were common with active treatment. The drugs are not peptides themselves — they stimulate peptide release — so their effects depend on the body's ability to produce these hormones. Blood pressure was an exploratory endpoint, not a primary outcome. Longer and larger trials are needed."},{"rthcId":"RPEP-10564","title":"Protein hydrolysates with ACE-I inhibitory activity from amaranth seeds fermented with Enterococcus faecium-LR9: Identification of peptides and molecular docking.","authors":"Cruz-Casas, Dora Elisa; Ramos-González, Rodolfo; Prado-Barragán, Lilia Arely; Iliná, Anna; Aguilar, Cristóbal N; Rodríguez-Herrera, Raúl; Tsopmo, Apollinaire; Flores-Gallegos, Adriana Carolina","year":2025,"journal":"Food chemistry, 464(Pt 1), 141598","doi":"10.1016/j.foodchem.2024.141598","pmid":"39413603","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10565","title":"Linear and Polyvalent Peptides with Potent Antimicrobial Activity Against Sensitive and Multidrug-Resistant E. c oli Clinical Isolates.","authors":"Cuero-Amu, Kelin; Daniela Bonilla-Velásquez, Laura; Vargas-Casanova, Yerly; Lucía Leal-Castro, Aura; Marcela Parra-Giraldo, Claudia; Giselle López-Sánchez, Amalia; Fierro-Medina, Ricardo; García-Castañeda, Javier; Rivera-Monroy, Zuly","year":2025,"journal":"Chemistry & biodiversity, 22(3), e202401734","doi":"10.1002/cbdv.202401734","pmid":"39486005","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10566","title":"α cells use both PC1/3 and PC2 to process proglucagon peptides and control insulin secretion.","authors":"Cui, Canqi; Leander, Danielle C; Gray, Sarah M; El, Kimberley; Chen, Alex; Grimsrud, Paul A; Becker, Jessica O; Taylor, Austin; Zhang, Guo-Fang; Sloop, Kyle W; Verchere, C Bruce; Hoofnagle, Andrew N; D'Alessio, David A; Campbell, Jonathan E","year":2025,"journal":"Science advances, 11(38), eady8048","doi":"10.1126/sciadv.ady8048","pmid":"40971442","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10567","title":"Factors influencing unplanned readmission within 30 days in patients with heart failure and their predictive value: a prospective study.","authors":"Cui, Lingling; Wei, Xiaolei; Liang, Tao; Yan, Rui; Du, Minyu; Alimire, Tusiyiti; Huang, Yuyang; Wang, Hua","year":2025,"journal":"BMC cardiovascular disorders, 25(1), 269","doi":"10.1186/s12872-025-04674-z","pmid":"40200138","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10568","title":"Quantitative Cell Type-Specific Immunopeptidome Analysis of Macrophage and Tumor Coevolution Reveals Therapeutic MHC-I Peptides in Glioblastoma.","authors":"Cui, Yufei; Phuong, Kien; Abdelfattah, Nouran S; Temple, Heidi M; Maiorino, Laura; Kim, B J; Dye, Jonathan; Yu, Kenny Kwok Hei; Spranger, Stefani; Irvine, Darrell J; White, Forest M","year":2025,"journal":"Cancer research, 85(24), 4958-4976","doi":"10.1158/0008-5472.CAN-24-4674","pmid":"40966317","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10569","title":"Animal models for development of anti-obesity drugs in the age of GLP-1 agents.","authors":"Culver, Alexander; Stayrook, Keith; Comerota, Michele; Oblak, Adrian; Burris, Thomas","year":2025,"journal":"Expert opinion on drug discovery, 20(7), 913-925","doi":"10.1080/17460441.2025.2507766","pmid":"40380806","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10570","title":"evoke and evoke+: design of two large-scale, double-blind, placebo-controlled, phase 3 studies evaluating efficacy, safety, and tolerability of semaglutide in early-stage symptomatic Alzheimer's disease.","authors":"Cummings, Jeffrey L; Atri, Alireza; Feldman, Howard H; Hansson, Oskar; Sano, Mary; Knop, Filip K; Johannsen, Peter; León, Teresa; Scheltens, Philip","year":2025,"journal":"Alzheimer's research & therapy, 17(1), 14","doi":"10.1186/s13195-024-01666-7","pmid":"39780249","tags":[],"studyType":"clinical trial protocol","evidenceStrength":"not yet available (phase 3 trial design)","keyFinding":"This paper describes the design of evoke and evoke+ — two large-scale, randomized, double-blind, placebo-controlled phase 3 trials testing oral semaglutide (14 mg daily) as a disease-modifying treatment for early-stage Alzheimer's disease. Each trial targets 1,840 participants (3,680 total) aged 55-85 with mild cognitive impairment or mild dementia due to Alzheimer's confirmed by amyloid biomarkers. Treatment lasts 156 weeks (104-week main phase + 52-week blinded extension). The primary endpoint is change in Clinical Dementia Rating - Sum of Boxes (CDR-SB) at 104 weeks. The trials also explore effects on AD biomarkers and neuroinflammation through plasma and CSF sub-studies.","whyItMatters":"These are the first large-scale trials testing whether semaglutide — already widely used for diabetes and obesity — can modify the course of Alzheimer's disease. The hypothesis is that GLP-1 receptor agonists could protect the brain through anti-inflammatory, vascular, and neuroprotective mechanisms. If successful, this would be transformative: semaglutide has an established safety profile, is already mass-produced, and could be rapidly deployed for Alzheimer's — unlike the expensive and complex amyloid-targeting antibodies (lecanemab, donanemab) that currently dominate the field.","specificNumbers":"3,680 planned participants (1,840 per trial) · 156 weeks treatment · Oral semaglutide 14 mg/day · CDR-SB primary endpoint · CSF sub-study n=210 · Enrollment: May 2021 - Sep 2023","methodology":"Two parallel phase 3 RCTs with identical design. Eligible participants have early-stage symptomatic AD (MCI or mild dementia) with confirmed amyloid pathology (PET or CSF). After screening, participants are randomized 1:1 to oral semaglutide or placebo with an 8-week dose escalation (3mg → 7mg → 14mg). The primary endpoint is CDR-SB change from baseline to week 104. Secondary outcomes include AD biomarkers in plasma and CSF (neuroinflammation markers in a 210-participant sub-study).","limitations":"This is a trial design paper — no results are reported yet. The trials enrolled participants with early-stage AD, so results won't address whether semaglutide helps moderate or advanced Alzheimer's. The oral formulation of semaglutide has lower bioavailability than injectable versions, which may affect brain penetration. The 104-week primary endpoint is lengthy, and dropout rates could be significant. The trial results were expected September 2025 and the extension October 2026."},{"rthcId":"RPEP-10571","title":"The Influence of GLP-1 Receptor Agonists on Five-Year Mortality in Colon Cancer Patients.","authors":"Cuomo, Raphael E","year":2025,"journal":"Cancer investigation, 43(10), 982-991","doi":"10.1080/07357907.2025.2585512","pmid":"41216819","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10572","title":"Impact of GLP-1 Receptor Agonists on Whole-Gut Gastrointestinal Motility Using Wireless Motility Capsule: A Descriptive Single-Center Case Series.","authors":"Cymbal, Michael; Naseem, Zehra; Hoxha, Din; Garg, Samita","year":2025,"journal":"ACG case reports journal, 12(8), e01789","doi":"10.14309/crj.0000000000001789","pmid":"40761333","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Using wireless motility capsule testing, researchers measured transit times throughout the entire digestive tract in 10 patients taking GLP-1 receptor agonists. Delayed gastric emptying was observed in 80% of patients (8 out of 10). Delayed whole-gut transit was seen in 44% of patients.\n\nNotably, the 3 patients on semaglutide at 1 mg had the longest gastric emptying times, the most delayed whole-gut transit, and were the only patients who also showed delayed small bowel transit time. This suggests semaglutide may have more pronounced effects on gut motility compared to other GLP-1 drugs in this series.","whyItMatters":"GLP-1 drugs like semaglutide and tirzepatide are now taken by millions of people. While stomach-slowing effects are well known, this study provides some of the first data showing these drugs may affect motility throughout the entire digestive tract. Understanding this is important for managing side effects like constipation, bloating, and gastroparesis that many patients experience.","specificNumbers":"","methodology":"This was a retrospective case series at a single medical center. Researchers reviewed records of 10 patients who were taking GLP-1 receptor agonists and had undergone wireless motility capsule testing — a procedure where patients swallow a small electronic capsule that measures pressure, pH, and transit time as it passes through the stomach, small intestine, and colon.","limitations":"This was a very small retrospective case series with only 10 patients at a single center, so the findings cannot be generalized. There was no control group for comparison. Patients were tested for existing GI complaints (constipation or gastroparesis), which may bias toward those already experiencing motility problems. Different patients were on different GLP-1 drugs at different doses, making direct drug comparisons unreliable."},{"rthcId":"RPEP-10573","title":"The relationship of temperamental, biochemical trait variables determining appetitive behaviour and alcohol-dependent individuals' health status and nutrition - preliminary study.","authors":"Czarnecki, Damian; Chodkiewicz, Jan; Długosz, Anna; Budzyński, Jacek; Marszałł, Michał P; Waszkiewicz, Napoleon; Kułak-Bejda, Agnieszka; Gorzkiewicz, Marta; Junkiert-Czarnecka, Anna; Michalska, Małgorzata; Żekanowska, Ewa; Ziółkowski, Marcin","year":2025,"journal":"Postepy psychiatrii neurologii, 34(4), 243-252","doi":"10.5114/ppn.2025.156747","pmid":"41488579","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10574","title":"(Pro)renin Receptor Blockade Prevents Increases in Systolic Blood Pressure, Sodium Retention, and αENaC Protein Expression in the Kidney of 2K1C Goldblatt Mice.","authors":"Cárdenas, Pilar; Cid-Salinas, Catalina; León, Allison C; Castillo-Geraldo, Juan; de Oliveira, Lilian Caroline Gonçalves; Yokota, Rodrigo; Vallotton, Zoe; Casarini, Dulce Elena; Prieto, Minolfa C; Lorca, Ramón A; Gonzalez, Alexis A","year":2025,"journal":"International journal of molecular sciences, 26(9)","doi":"10.3390/ijms26094177","pmid":"40362413","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10575","title":"Protein-Based Nanostructures: Column-free Biosynthesis of Bundlemer Peptides with Programmable, Orthogonally Reactive Handles for Nanomaterial Construction.","authors":"D'Ambrosio, Caitlin; Massad, Nadim; McCahill, Amanda L; Rears, William; Rouviere, Pierre; Saven, Jeffery G; Pochan, Darrin J; Kloxin, Christopher J; Kloxin, April M; Chen, Wilfred","year":2025,"journal":"ACS applied materials & interfaces, 17(51), 68992-69003","doi":"10.1021/acsami.5c17204","pmid":"41369150","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10576","title":"Glucagon-like peptide-1 receptor agonists for the treatment of obstructive sleep apnea.","authors":"D'Annibale, Danielle A; Mimoto, Mizuho; McCowen, Karen C; Malhotra, Atul","year":2025,"journal":"Current opinion in pulmonary medicine, 31(6), 591-596","doi":"10.1097/MCP.0000000000001208","pmid":"40855981","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10577","title":"Long-acting hydrogel-based depot formulations of tirzepatide and semaglutide for the management of type 2 diabetes and weight.","authors":"d'Aquino, Andrea I; Dong, Changxin; Nguyen, Leslee T; Yan, Jerry; Jons, Carolyn K; Saouaf, Olivia M; Song, Ye Eun; Eckman, Noah; Kapasi, Sara; Williams, Christian Milton; Doulames, Vanessa Madelyn; Sen, Samya; Manna, Manoj K; Alakesh, Alakesh; Lu, Katie; Hall, Ian; Appel, Eric A","year":2025,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2025.07.02.662867","pmid":"40631235","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A single injection of hydrogel-based depot formulations of either semaglutide or tirzepatide maintained therapeutic drug levels for over 6 weeks in a rat diabetes model. These single-dose formulations were equally effective at controlling blood glucose and body weight as daily injections of the same drugs in standard formulations. The hydrogel depot technology is easy to manufacture, injectable, and biocompatible, potentially enabling months-long treatment intervals.","whyItMatters":"Current GLP-1 drugs require weekly injections, which many patients find burdensome and leads to poor adherence. A single injection lasting 6+ weeks — or potentially months — could dramatically improve patient compliance and outcomes. For the millions of people who need these peptide drugs but struggle with regular injections, this technology could be transformative.","specificNumbers":"Single injection · >6 weeks drug release · equivalent to daily injections for glucose control and weight · both semaglutide and tirzepatide formulated · rat diabetes model · injectable hydrogel depot · excellent biocompatibility","methodology":"Researchers developed injectable hydrogel depots loaded with semaglutide or tirzepatide. The formulations were tested in a rat model of diabetes. Drug levels were measured over 6+ weeks after a single injection. Blood glucose regulation and body weight were compared between single hydrogel depot injections and daily standard injections of the same drugs.","limitations":"This is a preprint (bioRxiv) that has not yet undergone peer review. The study used a rat model; pharmacokinetics in larger animals and humans may differ significantly. The 6-week release window, while impressive, has not been confirmed in primates or humans. Manufacturing scale-up and regulatory pathway for a hydrogel depot GLP-1 formulation would be complex. Whether steady-state drug levels from a depot formulation produce the same clinical effects as pulsed weekly dosing is unknown."},{"rthcId":"RPEP-10578","title":"Immunization with peptide encapsulated within synthetic spores activates T cell responses and reduces tumor growth.","authors":"D'Atri, Domenico; Tondini, Elena; Machinandiarena, Federico; Kong, Minsuk; Mia, Alilin; Gallardo, Devorah; Tanner, Kandice; Hewitt, Stephen M; Fitzgerald, David J; Ramamurthi, Kumaran S","year":2025,"journal":"mBio, 16(10), e0225625","doi":"10.1128/mbio.02256-25","pmid":"40937857","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10579","title":"Snake Venom Peptide Fractions from Bothrops jararaca and Daboia siamensis Exhibit Differential Neuroprotective Effects in Oxidative Stress-Induced Zebrafish Models.","authors":"da Cunha E Silva, Felipe Assumpção; Silva, Brenda Rufino da; Barros, Leticia Ribeiro de; Beraldo-Neto, Emidio; Maleski, Adolfo Luis Almeida; Alberto-Silva, Carlos","year":2025,"journal":"Pharmaceuticals (Basel, Switzerland), 18(5)","doi":"10.3390/ph18050678","pmid":"40430497","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10580","title":"Efficacy of different cannabinoid compounds on migraine-like responses in female rats.","authors":"da Luz, Fernanda Mariano Ribeiro; Kaup, Alexandre Ottoni; Baggio, Darciane Favero; Costa, Flavio Henrique de Rezende; Chichorro, Juliana Geremias","year":2025,"journal":"Cephalalgia : an international journal of headache, 45(10), 3331024251386794","doi":"10.1177/03331024251386794","pmid":"41129688","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10581","title":"Molecular Mechanisms of Glucocorticoid Action in Migraine: A Systematic Review of Neuroinflammatory and Vascular Pathways.","authors":"da Silva Lopes, Luciano; Krymchantowski, Abouch; Jevoux, Carla; Krymchantowski, Ana Gabriela; Maria Coelho de Moura, Camila M; Soares, Adriana A; de Sá, Marco Antônio Pereira; Val, Sabrina Nayara de Araújo; Dos Santos, Renato Mendes; Silva-Néto, Raimundo Pereira","year":2025,"journal":"Cureus, 17(11), e96074","doi":"10.7759/cureus.96074","pmid":"41357008","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The systematic review of 26 articles (2004-2024) identified multiple molecular mechanisms by which glucocorticoids alleviate migraine:\n\n- Reduced calcitonin gene-related peptide (CGRP) levels — CGRP is a neuropeptide central to migraine pathophysiology\n- Decreased matrix metalloproteinase-9 (MMP-9) expression — MMP-9 degrades blood-brain barrier integrity\n- Inhibited nitric oxide synthesis — nitric oxide drives vasodilation and sensitization\n- Modulated transcription factors NF-κB and AP-1 — master regulators of inflammatory gene expression\n- Reduced pro-inflammatory cytokines IL-1β and TNF-α\n- Limited prostaglandin synthesis via COX-2 inhibition\n\nThese pathways collectively suppress both central and peripheral sensitization in the trigeminovascular system.","whyItMatters":"Migraine affects over a billion people worldwide, and while new CGRP-targeted therapies have transformed treatment, glucocorticoids remain important for acute severe attacks and treatment-resistant cases. Understanding that glucocorticoids work partly by reducing CGRP — the same neuropeptide targeted by the newest migraine drugs — helps explain their effectiveness and may guide more strategic use. This review suggests glucocorticoids have underappreciated value specifically in migraines with strong neuroinflammatory features.","specificNumbers":"","methodology":"The authors conducted a systematic review of literature published between 2004 and 2024, selecting 26 articles that examined the molecular mechanisms of glucocorticoid action in migraine. The analysis focused on neuroinflammatory mediators, blood-brain barrier integrity, and nociceptive signaling pathways. Studies were evaluated for their contributions to understanding how glucocorticoids affect specific molecular targets relevant to migraine pathogenesis.","limitations":"As a systematic review, the quality and conclusions depend on the underlying studies, which likely varied in design and rigor. The review covers mechanisms identified in laboratory and clinical studies but does not perform a meta-analysis of clinical outcomes. The Cureus publication venue, while peer-reviewed, has different editorial standards than top-tier journals. The specific contexts in which glucocorticoids are most beneficial for migraine (dose, timing, patient subtype) remain incompletely defined."},{"rthcId":"RPEP-10582","title":"Evaluation of cardiac markers in patients with breast cancer receiving antineoplastic treatment: a systematic review.","authors":"da Silva Soares, Tiago Nunes; Gascón, Thaís Moura; Fonseca, Fernando Luiz Affonso; Murad, Neif; de Carvalho, Samantha Sanches; Veiga, Glaucia Luciano da; Alves, Beatriz da Costa Aguiar; Pereira, Edimar Cristiano","year":2025,"journal":"Chinese clinical oncology, 14(6), 76","doi":"10.21037/cco-24-136","pmid":"41492869","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10583","title":"7-Nitroindazole, an nNOS inhibitor, reduces migraine-like nociception, demyelination, and anxiety-like behavior in a mouse model of relapsing-remitting multiple sclerosis.","authors":"da Silva, Brenda; Viero, Fernanda Tibolla; de David Antoniazzi, Caren Tatiane; Kudsi, Sabrina Qader; Peres, Diulle Spat; Morais, Ricardo Iuri Felix; Pereira, Leonardo Gomes; Trevisan, Gabriela","year":2025,"journal":"Nitric oxide : biology and chemistry, 159, 51-62","doi":"10.1016/j.niox.2025.09.003","pmid":"40947004","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10584","title":"What Clinicians Need to Know About Glucagon-like Peptide 1 Agonists.","authors":"da Silva, Dimitri Luz Felipe; Singla, Shikha; Mease, Philip J","year":2025,"journal":"The Journal of rheumatology, 52(Suppl 3), 52-54","doi":"10.3899/jrheum.2025-0531","pmid":"40816736","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 receptor agonists, including dual GLP-1/GIP agonists like tirzepatide, demonstrate benefits beyond blood sugar control — including weight loss, improved metabolic health, and potential immune response modulation. Recent studies suggest they may help manage psoriasis and psoriatic arthritis in patients with obesity by reducing inflammation and addressing metabolic abnormalities like insulin resistance and hyperlipidemia. However, the evidence supporting their use specifically for psoriasis and psoriatic arthritis remains limited.","whyItMatters":"Psoriasis and psoriatic arthritis affect millions of people, and obesity significantly worsens both conditions while making standard treatments less effective. If GLP-1 peptide agonists can simultaneously address weight, metabolic dysfunction, and autoimmune inflammation, they could fill a major unmet need — particularly for the large proportion of psoriasis patients who also have metabolic syndrome. This represents a potential paradigm shift from treating these conditions in isolation to addressing the metabolic-immune axis as a whole.","specificNumbers":"","methodology":"This is a conference report summarizing a presentation given at the GRAPPA (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis) 2024 annual meeting. It reviews the current state of evidence on GLP-1 receptor agonists as potential treatments for psoriasis and psoriatic arthritis, particularly in patients with concurrent obesity.","limitations":"This is a conference summary, not a systematic review or original research. It does not present new clinical data. The evidence for GLP-1 agonists specifically treating psoriasis and psoriatic arthritis is acknowledged as limited. No specific clinical trial results, patient numbers, or effect sizes are provided in the abstract. The dual mechanism (anti-inflammatory vs. weight-loss-mediated improvement) has not been clearly separated."},{"rthcId":"RPEP-10585","title":"Alginate-based hydrogels for sustained antimicrobial peptide delivery to enhance wound healing in diabetes.","authors":"Da Silva, Jessica; Leal, Ermelindo C; Gomes, Ana; Gomes, Paula; Calheiros, Daniela; Gonçalves, Teresa; Carvalho, Eugénia; Silva, Eduardo A","year":2025,"journal":"Biomaterials advances, 175, 214337","doi":"10.1016/j.bioadv.2025.214337","pmid":"40359773","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Alginate-based hydrogels provided sustained hBD-2 release for over 3 days with stable properties across pH 6-8. In vitro, hBD-2 hydrogels showed excellent biocompatibility and superior cell migration promotion compared to PP4-3.1 hydrogels. In a diabetic mouse wound model, hBD-2 hydrogels significantly: accelerated wound closure, improved re-epithelialization and tissue remodeling, reduced microbial wound load, decreased M1-like macrophages and M1/M2 ratio (shifting toward anti-inflammatory phenotype), reduced CD3+ cells, lowered reactive oxygen species levels, and increased neovascularization and collagen deposition.","whyItMatters":"Diabetic foot ulcers affect approximately 25% of diabetes patients and cause over 100,000 amputations annually in the US alone. Current treatments fail to address all the factors that impair healing. This hBD-2 hydrogel simultaneously fights infection, calms inflammation, reduces oxidative damage, and promotes tissue repair — a multi-pronged approach matching the complexity of diabetic wound pathology.","specificNumbers":"","methodology":"Alginate hydrogels were designed to deliver two AMPs (hBD-2 and PP4-3.1). Physical characterization included rheology, swelling, porosity, and release kinetics. In vitro testing assessed biocompatibility and cell migration. hBD-2 hydrogels were tested in a streptozotocin-induced diabetic mouse wound model, with outcomes including wound closure rate, histological maturation, microbial load, inflammatory markers (macrophage phenotype, CD3+ cells), ROS levels, neovascularization, and collagen deposition.","limitations":"This is a preclinical study using a mouse diabetic wound model. Mouse wound healing differs from human (contraction vs granulation). The streptozotocin model mimics type 1 diabetes more than type 2, which causes most diabetic foot ulcers. Specific wound closure rates and statistical comparisons were not detailed in the abstract. Long-term outcomes and comparison to existing clinical wound treatments were not assessed."},{"rthcId":"RPEP-10586","title":"Seasonal and nutritional modulation of honeybee olfactory learning by the short neuropeptide F.","authors":"da Silva, Rafael Carvalho; Baracchi, David; Ricciardi, Giulia; Giurfa, Martin; de Brito Sanchez, Maria Gabriela","year":2025,"journal":"Proceedings. Biological sciences, 292(2051), 20250655","doi":"10.1098/rspb.2025.0655","pmid":"40695342","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10587","title":"Anorexigenic and anti-inflammatory signaling pathways of semaglutide via the microbiota-gut--brain axis in obese mice.","authors":"da Silva, Rodrigo Soares; de Paiva, Igor Henrique Rodrigues; Mendonça, Ingrid Prata; de Souza, José Roberto Botelho; Lucena-Silva, Norma; Peixoto, Christina Alves","year":2025,"journal":"Inflammopharmacology, 33(2), 845-864","doi":"10.1007/s10787-024-01603-y","pmid":"39586940","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10588","title":"Postbiotic-Mediated Obesity Reduction via Bioactive Peptide ETLVK and Gut Microbiota in HFD Mice.","authors":"Da, Jia-Yi; Wang, Chang; Feng, Xiaomin; Li, Han-Lu; Zhong, Feiliang; Luo, Xue-Gang","year":2025,"journal":"Journal of agricultural and food chemistry, 73(36), 22436-22447","doi":"10.1021/acs.jafc.5c07319","pmid":"40859113","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The probiotic bacterium L. plantarum TCCC11824 produces bioactive peptides that reduce obesity in mice fed a high-fat diet. The crushed bacterial supernatant (LpS) significantly improved blood lipid profiles, reduced liver injury, suppressed inflammation in liver and fat tissue, decreased ectopic fat accumulation, and positively shifted gut microbiota composition.\n\nResearchers identified that the 3-10 kDa fraction of LpS strongly inhibited pancreatic cholesterol esterase and lipase and suppressed HMGCR expression in lipid-disordered cells. Among five predicted candidate peptides (IPR, IEK, PGDR, ETLVK, and QAEQLR), LC-MS/MS confirmed ETLVK as the key peptide responsible for the lipid-lowering effect.","whyItMatters":"Understanding exactly which molecules from probiotic bacteria produce health benefits has been a major challenge. This study pinpoints a specific five-amino-acid peptide (ETLVK) as a key active component, providing a molecular explanation for how this probiotic fights obesity. This could lead to targeted peptide-based therapies for metabolic disorders rather than relying on whole probiotic formulations.","specificNumbers":"5 candidate peptides predicted · ETLVK confirmed as key active peptide · 3-10 kDa bioactive fraction · Inhibited pancreatic cholesterol esterase + lipase · Suppressed HMGCR expression","methodology":"Researchers fed mice a high-fat diet to induce obesity, then treated them with crushed supernatant from L. plantarum TCCC11824. They analyzed blood lipids, liver injury markers, inflammation, fat distribution, and gut microbiota composition. The active fraction was identified through ultrafiltration, and candidate peptides were predicted using bioinformatics from the full-length protein sequence and confirmed via LC-MS/MS mass spectrometry.","limitations":"This is an animal study in mice; effects in humans remain unconfirmed. The study used a bacterial supernatant rather than a purified peptide for most in vivo experiments. The long-term effects and optimal dosing of ETLVK itself have not been established."},{"rthcId":"RPEP-10589","title":"Amycretin, a novel, unimolecular GLP-1 and amylin receptor agonist administered subcutaneously: results from a phase 1b/2a randomised controlled study.","authors":"Dahl, Kirsten; Toubro, Søren; Dey, Sohan; Duque do Vale, Ruben; Flint, Anne; Gasiorek, Agnes; Heydorn, Arne; Jastreboff, Ania M; Key, Cassandra; Petersen, Signe Beck; Vegge, Andreas; Adelborg, Kasper","year":2025,"journal":"Lancet (London, England), 406(10499), 149-162","doi":"10.1016/S0140-6736(25)01185-7","pmid":"40550231","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10590","title":"Patient experiences with group consultations when treated with semaglutide for obesity: a qualitative case study in a Danish general practice.","authors":"Dahl-Larsen, Rasmus; Jakobsen, P R; Søndergaard, Jens; Henriksen, Jan Erik; Assing Hvidt, Elisabeth","year":2025,"journal":"BMJ open, 15(7), e093357","doi":"10.1136/bmjopen-2024-093357","pmid":"40713055","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10591","title":"Downregulation of the NPY-Y1R system in Grpr neurons results in mechanical and chemical hyperknesis in chronic itch.","authors":"Dai, Danqing; Li, Zongxi; Zhao, Tiantian; Li, Zhen; Tang, Yali; Li, Xiujuan; Gao, Xiao-Fei; Xiong, Lize","year":2025,"journal":"Neurobiology of disease, 206, 106806","doi":"10.1016/j.nbd.2025.106806","pmid":"39827968","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10592","title":"GLP-1 Receptor Agonists and Cancer Risk in Adults With Obesity.","authors":"Dai, Hao; Li, Yongqiu; Lee, Yao An; Lu, Ying; George, Thomas J; Donahoo, William T; Lee, Kelvin P; Nakshatri, Harikrishna; Allen, John; Guo, Yi; Sun, Ramon C; Guo, Jingchuan; Bian, Jiang","year":2025,"journal":"JAMA oncology, 11(10), 1186-1193","doi":"10.1001/jamaoncol.2025.2681","pmid":"40839273","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10593","title":"GLP-1 Receptor Agonists and Cardiovascular Events in Adults with Obesity and Autoimmune Disease: A Target Trial Emulation.","authors":"Dai, Hao; Lee, Yao An; Natalie, Austin; Jackson, Whitney; Pham, Angela; Levine, Jake; Radwan, Rotana; Guo, Jingchuan; Bian, Jiang; Sheer, Amy J","year":2025,"journal":"medRxiv : the preprint server for health sciences","doi":"10.1101/2025.11.10.25339912","pmid":"41292651","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In the propensity score-matched cohort of 26,408 adults with obesity and autoimmune disease, GLP-1RA use was associated with significantly lower hazards for multiple outcomes compared to non-use:\n\n- Stroke/TIA: HR 0.87 (95% CI: 0.76-0.99; P = 0.039) — 13% reduction\n- Pulmonary embolism: HR 0.69 (95% CI: 0.56-0.86; P = 0.001) — 31% reduction\n- Venous thromboembolism: HR 0.83 (95% CI: 0.72-0.95; P = 0.007) — 17% reduction\n- ED visits: HR 0.79 (95% CI: 0.75-0.83; P < 0.001) — 21% reduction\n- All-cause mortality: HR 0.56 (95% CI: 0.47-0.66; P < 0.001) — 44% reduction\n\nIncidence rates per 1,000 person-years were consistently lower for GLP-1RA users across thromboembolic events.","whyItMatters":"People with autoimmune diseases (like rheumatoid arthritis, lupus, psoriasis, and inflammatory bowel disease) already have heightened cardiovascular risk from chronic inflammation. When combined with obesity — another inflammatory condition — the risk compounds dangerously. This study provides the first large-scale evidence that GLP-1RAs may be particularly beneficial for this dual-risk population. The 44% mortality reduction is especially striking and suggests these peptide drugs may address the underlying inflammatory pathology driving risk in autoimmune patients.","specificNumbers":"","methodology":"Retrospective cohort study emulating a target trial using 2014-2024 electronic health records from the OneFlorida+ network (21 million individuals across Florida, Georgia, and Alabama). Adults with obesity and autoimmune disease who met anti-obesity medication eligibility criteria were included. Propensity score matching (1:1) with a time-dependent framework was applied to balance baseline characteristics between 13,204 GLP-1RA users and 13,204 non-users. Hazard ratios were calculated for cardiovascular, thromboembolic, healthcare utilization, and mortality outcomes.","limitations":"This is an observational study, not a randomized trial, so residual confounding is possible despite propensity score matching. The study used EHR data which may have coding inaccuracies and missing data. Specific autoimmune diseases were grouped together, and benefits may vary by condition. The preprint has not yet undergone peer review. The 44% mortality reduction is very large and should be interpreted cautiously until confirmed in randomized trials. Healthy user bias (GLP-1RA users may be more health-conscious) could inflate benefits."},{"rthcId":"RPEP-10594","title":"GLP-1 Receptor Agonists and Acute Diabetes Complications in Adults with Type 1 Diabetes: A Target Trial Emulation.","authors":"Dai, Hao; Lee, Yao An; Radwan, Rotana; Sheer, Amy J; Hannon, Tamara S; Hayes, Matthew R; Sun, Ramon C; Bian, Jiang; Guo, Jingchuan","year":2025,"journal":"medRxiv : the preprint server for health sciences","doi":"10.1101/2025.11.10.25339908","pmid":"41292646","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10595","title":"GLP-1 Receptor Agonists and Substance Use Disorders in Older Adults With Type 2 Diabetes: A Target Trial Emulation.","authors":"Dai, Hao; Radwan, Rotana M; Scheiffele, Grant D; Tang, Huilin; Sheer, Amy; Lin, Hsin-Yueh; Zhang, Pengyue; Adirika, Darlene; Luong, Kate; Bian, Jiang; Guo, Jingchuan","year":2025,"journal":"Obesity (Silver Spring, Md.)","doi":"10.1002/oby.70024","pmid":"40954547","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In the GLP-1RA vs DPP4i comparison (n=4,920 matched pairs), GLP-1RA users had significantly lower risk of SUD hospitalization (HR 0.76; 95% CI: 0.67-0.86) and OUD hospitalization (HR 0.64; 95% CI: 0.43-0.96). AUD hospitalization showed a non-significant trend (HR 0.76; 95% CI: 0.53-1.08). No significant differences were found between GLP-1RA and SGLT2i users (n=4,620 matched pairs).","whyItMatters":"Substance use disorders in elderly diabetic patients are underrecognized and undertreated. The possibility that GLP-1 drugs — already prescribed for diabetes — could simultaneously reduce addiction-related hospitalizations would be a remarkable dual benefit. The 36% reduction in opioid-related hospitalizations is particularly significant given the ongoing opioid crisis and the vulnerability of older adults to opioid complications.","specificNumbers":"","methodology":"Retrospective cohort study using 2016-2020 Medicare claims data in a target trial emulation framework. Adults ≥65 with T2D and SUD were compared: GLP-1RA new users versus DPP4i or SGLT2i new users. Propensity score 1:1 matching controlled for confounders. Cox proportional hazards models with intention-to-treat approach assessed hospitalization outcomes.","limitations":"Retrospective observational study using claims data, which cannot establish causation. The comparison with SGLT2i showed no difference, weakening the case for a unique GLP-1R-mediated reward pathway effect. Medicare claims may undercount substance use episodes. The older adult population (≥65) may not reflect younger SUD populations. SUD severity and treatment engagement were not captured. The opioid result confidence interval was wide (0.43-0.96)."},{"rthcId":"RPEP-10596","title":"Two-pronged approach: Therapeutic effect of biological scaffold combined with immune intervention and β-cell replacement on type 1 diabetic mice.","authors":"Dai, Le; Wang, Qing","year":2025,"journal":"Diabetes, obesity & metabolism, 27(6), 3464-3476","doi":"10.1111/dom.16373","pmid":"40150917","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10597","title":"Chemoenzymatic Synthesis of Rhamnolipid-Modified Exendin-4: A Dual Approach for Long-Acting Glycemic Control through Endogenous Antibody Recruitment and Albumin Interaction.","authors":"Dai, Shijie; Liu, Haiyan; Mi, Baojing; Li, Yanchu; Zhao, Kai; Hong, Haofei; Wu, Zhimeng","year":2025,"journal":"Journal of medicinal chemistry, 68(21), 23324-23334","doi":"10.1021/acs.jmedchem.5c02146","pmid":"41163197","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10598","title":"Exercise improves endothelial progenitor cell's function in mice with Type 2 diabetes via gut microbiota modulation.","authors":"Dai, Xia; Chen, Haiyan; Zhang, Milei; Yang, Qiong; Huang, Zheng; Tang, LiAn","year":2025,"journal":"Frontiers in cellular and infection microbiology, 15, 1606652","doi":"10.3389/fcimb.2025.1606652","pmid":"40951313","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Eight weeks of exercise (aerobic, resistance, or combined) in diabetic mice altered gut microbiota composition, increasing Prevotellaceae and Ligilactobacillus. Fecal microbiota transplantation (FMT) from exercised donors to recipient mice:\n\n- Elevated plasma GLP-1 by 0.92 pmol/L (P < 0.001) — surpassing exercise's own modest, non-significant GLP-1 increase\n- Enriched Akkermansia in recipient gut\n- Enhanced endothelial progenitor cell proliferation (P < 0.007) and migration (P < 0.05)\n- Reduced blood glucose by 9.22 mmol/L (P < 0.001)\n- Exercise alone reduced body weight by 10.58 g (P < 0.001, aerobic training)","whyItMatters":"This study reveals a fascinating mechanism: exercise increases GLP-1 (the same peptide targeted by semaglutide and other drugs) through changing gut bacteria. This means the gut microbiome may be a natural 'pharmacy' for GLP-1 production, and therapies targeting specific gut bacteria could potentially boost endogenous GLP-1 without drugs.","specificNumbers":"","methodology":"Type 2 diabetic mice underwent 8 weeks of aerobic, resistance, or combined exercise. Mice with the best outcomes donated fecal material for gut microbiota transplantation to sedentary diabetic recipients. Both groups were assessed for glucose, weight, GLP-1 levels, gut bacterial composition (16S sequencing), and endothelial progenitor cell function (proliferation and migration assays).","limitations":"Mouse study results may not translate to humans. FMT from 'best performing' exercise mice introduces selection bias. The GLP-1 increase from FMT, while statistically significant, was modest in absolute terms. The mechanism by which specific gut bacteria increase GLP-1 secretion wasn't elucidated. Long-term effects and the durability of FMT benefits were not assessed."},{"rthcId":"RPEP-10599","title":"The impact of hyperglycemia on prognosis in chronic obstructive pulmonary disease patients with coronary heart disease: A five-year prospective study.","authors":"Dai, Zhongshang; He, Chenjie; Zeng, Huiui; Chen, Yan","year":2025,"journal":"PloS one, 20(12), e0335935","doi":"10.1371/journal.pone.0335935","pmid":"41348723","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10600","title":"Chemical coding of piglets small intestine neurons after prenatal exposure to β-hydroxy-β-methylbutyrate.","authors":"Dajnowska, Aleksandra; Kras, Katarzyna; Tomaszewska, Ewa; Dobrowolski, Piotr; Klebaniuk, Renata; Muszyński, Siemowit; Arciszewski, Marcin Bartłomiej","year":2025,"journal":"Journal of veterinary research, 69(2), 249-255","doi":"10.2478/jvetres-2025-0024","pmid":"40552032","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10601","title":"Generalizability of glucagon-like peptide 1 receptor agonist clinical trial results to product labeling and the real world.","authors":"Dal-Ré, Rafael","year":2025,"journal":"Annals of the New York Academy of Sciences, 1551(1), 15-18","doi":"10.1111/nyas.70025","pmid":"40760786","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10602","title":"Glucagon-Like Peptide-1 Receptor Agonists and Hepatocellular Carcinoma Prevention: A Meta-Analysis and Clinical Decision Framework.","authors":"Dalbeni, Andrea; Vicardi, Marco; Natola, Leonardo Antonio; Cattazzo, Filippo; Auriemma, Alessandra; Lombardi, Rosa; Cinque, Felice; Dalle Carbonare, Luca; Mantovani, Alessandro; Sacerdoti, David","year":2025,"journal":"Cancer medicine, 14(24), e71434","doi":"10.1002/cam4.71434","pmid":"41388641","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10603","title":"Managing glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors in clinical practice.","authors":"Dalpiaz, Hermann; Masi, Stefano; Piludu, Sara; Agnoletti, Davide; Piani, Federica; Fiorini, Giulia; Borghi, Claudio","year":2025,"journal":"Heart (British Cardiac Society)","doi":"10.1136/heartjnl-2024-324847","pmid":"40664497","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10604","title":"Comparative Effectiveness of Pharmacologic Treatments for the Prevention of Episodic Migraine Headache: A Systematic Review and Network Meta-analysis for the American College of Physicians.","authors":"Damen, Johanna A A; Yang, Bada; Idema, Demy L; Vernooij, Robin W M; Huis In 't Veld, Linde; Kusters, Mike; Spijker, Rene; van der Braak, Kim; Heus, Pauline; Jenniskens, Kevin; Hooft, Lotty","year":2025,"journal":"Annals of internal medicine, 178(3), 369-380","doi":"10.7326/ANNALS-24-00315","pmid":"39899873","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 61 studies (20,680 patients) evaluating 16 pharmacologic treatments for episodic migraine prevention:\n\n- No high-certainty evidence favored any one treatment over another for effectiveness\n- CGRP monoclonal antibodies probably resulted in fewer treatment discontinuations due to adverse events compared to topiramate (risk difference -16.2%, 95% CI: -18.4% to -12.8%; moderate-certainty evidence)\n- CGRP-mAbs may result in less migraine-related disability and improved quality of life compared to gepants (low-certainty evidence)\n- For most other comparisons, evidence was of low certainty, uncertain, or absent\n- Only 19 of 61 studies had low risk of bias","whyItMatters":"With over a dozen migraine prevention options available, clinicians and patients need guidance on which to choose first. This authoritative ACP-commissioned analysis reveals that the evidence doesn't strongly favor one drug over another for efficacy — making tolerability, cost, and patient preference more important in treatment selection. The better side-effect profile of CGRP antibodies compared to older drugs like topiramate is particularly relevant for shared decision-making.","specificNumbers":"","methodology":"This systematic review and network meta-analysis was commissioned by the American College of Physicians. Researchers searched MEDLINE, EMBASE, and Cochrane Central through April 2024 for randomized trials of pharmacologic migraine prevention in adults with episodic migraine. Only treatments previously shown to be superior to placebo were included. Data extraction was verified by a second reviewer. Risk of bias was assessed using the Cochrane tool, and evidence certainty was graded using GRADE methodology.","limitations":"Head-to-head comparisons between specific treatments were very limited, requiring indirect comparisons through the network meta-analysis. Evidence certainty was mostly low or insufficient. Minimal important differences for outcome measures were not well-established. Only 19 of 61 studies had low risk of bias. The analysis was limited to episodic migraine — chronic migraine was not included. Cost-effectiveness was not assessed despite being a key clinical consideration."},{"rthcId":"RPEP-10605","title":"Detection of Genes Associated with Polymyxin and Antimicrobial Peptide Resistance in Isolates of Pseudomonas aeruginosa.","authors":"Damtie, Meseret Alem; Vijay, Ajay Kumar; Willcox, Mark Duncan Perry","year":2025,"journal":"International journal of molecular sciences, 26(21)","doi":"10.3390/ijms262110499","pmid":"41226536","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 40 Pseudomonas aeruginosa isolates (from India and Australia):\n\n• 65% were resistant to polymyxin B; 80% to colistin\n• Polymyxin B MICs ranged from 0.5 to 512 µg/mL, with 22.5% being highly resistant (MIC ≥256 µg/mL)\n• Polymyxin B and colistin MICs were strongly correlated (Spearman's R ≥0.6, p≤0.001)\n• LL-37 (human cathelicidin) showed moderate correlation with polymyxin B, colistin, and Mel4\n• Mel4 (synthetic AMP) showed weaker correlations with polymyxins\n• SNP analysis identified nalC (E153Q/D) and mipB (V469M, G441S) variants as associated with MICs to all antimicrobials\n• Strains with MICs 64-512 µg/mL were significantly more likely to harbor these variants (p<0.05)","whyItMatters":"Antimicrobial peptides are one of the most promising alternatives to traditional antibiotics, but if bacteria already resistant to polymyxins can also resist AMPs, this undermines the entire strategy. The finding of shared resistance mechanisms between polymyxins and both natural human AMPs (LL-37) and synthetic peptides means that the superbug problem could extend to the next generation of antimicrobial peptide drugs before they even reach the market.","specificNumbers":"","methodology":"Forty Pseudomonas aeruginosa isolates, mostly from India and Australia, were tested for MICs to polymyxin B, colistin, LL-37 (human cathelicidin), and Mel4 (synthetic AMP) using broth microdilution in cation-adjusted Mueller-Hinton broth. Whole genome sequencing was performed and analyzed using NCBI BLAST. SNP-MIC associations were evaluated with Fisher's exact test. Correlation analysis used Spearman's rank correlation.","limitations":"Relatively small sample size (40 isolates). Isolates were predominantly from India and Australia, limiting geographic generalizability. The correlation between polymyxin and AMP resistance does not prove a causal shared mechanism. LL-37 and Mel4 are only two of many AMPs in development — other AMPs with different mechanisms may not show the same cross-resistance. Clinical relevance of in vitro MIC changes for AMPs has not been established."},{"rthcId":"RPEP-10606","title":"Cardiovascular risk associated with glucagon-like peptide-1 receptor agonists versus other conventional glucose-lowering drugs in patients with type-2 diabetes: protocol for a nationwide observational comparative study in routine care.","authors":"Danchin, Nicolas; Lemesle, Gilles; Mazighi, Mikael; Mohammedi, Kamel; Schiele, Francois; Sibon, Igor; Caron, Alexandre; Emery, Corinne; Nevoret, Camille; Vigié, Lucile; Massien, Christine; Detournay, Bruno; Fauchier, Laurent","year":2025,"journal":"BMJ open, 15(1), e087790","doi":"10.1136/bmjopen-2024-087790","pmid":"39788759","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10607","title":"\"Ozempic Face\" in Plastic Surgery: A Systematic Review of the Literature on GLP-1 Receptor Agonist Mediated Weight Loss and Analysis of Public Perceptions.","authors":"Daneshgaran, Giulia; Shauly, Orr; Gould, Daniel J","year":2025,"journal":"Aesthetic surgery journal. Open forum, 7, ojaf056","doi":"10.1093/asjof/ojaf056","pmid":"40626110","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10608","title":"Dual-Modified Mannose/RVG29 Peptide-Functionalized Lipid Nanoparticles Loaded With circHIPK2 siRNA Ameliorate Hypoxic-Ischemic Brain Damage in Neonatal Mice by Suppressing Astrocyte Activation.","authors":"Dang, Yinxia; Shen, Fuhui; Wang, Shengxia; Zhang, Yating; Lu, Xia; Qin, Dongyuan; Feng, Dan; Song, Yanjun; Cheng, Zihuan; Ma, Ruicong; Wang, Fan","year":2025,"journal":"Journal of integrative neuroscience, 24(12), 45212","doi":"10.31083/JIN45212","pmid":"41503997","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Dual-modified lipid nanoparticles functionalized with RVG29 peptide (for BBB penetration) and mannose (for astrocyte targeting) delivered circHIPK2 siRNA to the brain with high specificity. The 134 nm nanoparticles showed good stability and biosafety. CircHIPK2 silencing markedly suppressed astrocyte activation, reducing GFAP and IL-1β expression (p<0.0001 in vivo). Neurobehavioral testing showed significantly improved righting reflex, negative geotaxis, and spatial learning/memory in treated neonatal mice with hypoxic-ischemic brain damage.","whyItMatters":"Neonatal HIE affects 1–6 per 1,000 live births and can cause lifelong disability including cerebral palsy and cognitive impairment. The only current treatment is therapeutic hypothermia (cooling), which has limited efficacy. This study demonstrates a proof-of-concept for peptide-guided nanoparticle delivery of gene therapy directly to the brain cells responsible for neuroinflammation, offering a fundamentally new approach to treating newborn brain injury.","specificNumbers":"134 nm nanoparticle size · RVG29 peptide for brain targeting · Mannose for astrocyte targeting · Significant GFAP and IL-1β reduction (p<0.0001) · Improved neurobehavioral recovery","methodology":"Lipid nanoparticles were constructed with DSPE-PEG2000-RVG29 peptide and mannose surface modifications and loaded with circHIPK2 siRNA. Physicochemical properties, stability, and biocompatibility were characterized. Efficacy was tested in an in vitro oxygen-glucose deprivation model and in vivo in neonatal C57BL/6 mice with hypoxic-ischemic brain damage. Astrocyte activation markers (GFAP, IL-1β) were measured by western blot, qRT-PCR, and immunofluorescence. Neurobehavioral recovery was assessed by righting reflex, negative geotaxis, and Morris water maze tests.","limitations":"This is a preclinical mouse study — neonatal mice have a simpler brain structure and different BBB properties than human newborns. The long-term effects and safety of circHIPK2 silencing are unknown. Manufacturing scalability and regulatory pathway for this complex nanoparticle system are significant translational challenges. The specific timing window for treatment after birth injury was not extensively explored."},{"rthcId":"RPEP-10609","title":"Systematic review of peptide nanoparticles for improved diabetes outcomes: insights and opportunities.","authors":"Dangana, Reuben Samson; Okon, Michael Ben; Orire, Ikuomola Emmanuel; Sanusi, Idris Olatunji; Terkimbi, Swase Dominic; Aja, Patrick Maduabuchi; Abubakar, Ibrahim Babangida; Anyim, Godwin","year":2025,"journal":"Discover nano, 20(1), 41","doi":"10.1186/s11671-025-04215-9","pmid":"39961878","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10610","title":"Intrastrand Peptide Staples That Promote β-Sheet Folding, Self-Assembly, and Amyloid Seeding.","authors":"Dangi, Abha; Angera, Isaac J; Del Valle, Juan R","year":2025,"journal":"Journal of the American Chemical Society, 147(33), 29930-29938","doi":"10.1021/jacs.5c06944","pmid":"40778481","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10611","title":"An Observational Study of Cardiovascular Outcomes of Tirzepatide vs Glucagon-Like Peptide-1 Receptor Agonists.","authors":"Dani, Sourbha S; Makwana, Bhargav; Khadke, Sumanth; Kumar, Ashish; Jhund, Pardeep; Nasir, Khurram; Sattar, Naveed; Al-Kindi, Sadeer; Fonarow, Gregg; Butler, Javed; Bhatt, Deepak L; Kosiborod, Mikhail N; Nohria, Anju; Ganatra, Sarju","year":2025,"journal":"JACC. Advances, 4(5), 101740","doi":"10.1016/j.jacadv.2025.101740","pmid":"40447342","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10612","title":"Impact of GLP-1 receptor agonists on cardiovascular outcomes in patients with peripheral artery disease without diabetes: A propensity score-matched analysis.","authors":"Daniel, Emmanuel; El-Nayir, Mohammed; Ogunniyi, Kayode; Patel, Yash; Olayiwola, Paul; Oredipe, Omotola; Nwankwo, Henry; Nwaezeapu, Karldon; Ojo, Tioluwani","year":2025,"journal":"Journal of investigative medicine : the official publication of the American Federation for Clinical Research, 10815589251393978","doi":"10.1177/10815589251393978","pmid":"41137196","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10613","title":"A Retrospective Comparative Analysis of Cutaneous Adverse Reactions in GLP-1 Agonist Therapies.","authors":"Daniel, Sophia; Waggett, Stephanie; Lyles, Elliott; Sagut, Pelin; Shamaei Zadeh, Parisa; Marcelletti, Anthony; Stegura, Carol; Wine Lee, Lara","year":2025,"journal":"Journal of drugs in dermatology : JDD, 24(4), 413-415","doi":"10.36849/JDD.8605","pmid":"40196945","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10614","title":"Glucagon-like peptide-1 receptor agonism and end-organ protection.","authors":"Daniels, Samuel; Karlsson, Cecilia; Schrauwen, Patrick; Parker, Victoria E R","year":2025,"journal":"Trends in endocrinology and metabolism: TEM, 36(4), 301-315","doi":"10.1016/j.tem.2025.01.002","pmid":"39934020","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1RAs have established benefits in type 2 diabetes, body weight management, and cardiovascular risk protection. Beyond these, growing evidence supports organ-protective effects in multiple systems:\n\n- Renal: GLP-1RAs show kidney-protective effects that may slow chronic kidney disease progression\n- Hepatic: Benefits in non-alcoholic fatty liver disease/metabolic dysfunction-associated steatotic liver disease\n- Respiratory: Emerging evidence for lung-protective effects\n- Neurological: Potential neuroprotective benefits in neurodegenerative diseases\n\nThe review explores both weight-dependent and weight-independent mechanisms underlying these multi-organ benefits, suggesting that GLP-1 receptor signaling has direct protective effects on tissues throughout the body.","whyItMatters":"The discovery that a peptide from Gila monster venom could protect multiple organ systems represents one of the most remarkable translational stories in medicine. If GLP-1RAs can truly protect the heart, kidneys, liver, lungs, and brain, they could become the most widely prescribed drug class of the 21st century. Understanding which organ-protective effects are direct (via GLP-1 receptor signaling) versus indirect (via weight loss) is crucial for optimizing treatment and identifying which patients will benefit most.","specificNumbers":"","methodology":"Narrative review published in Trends in Endocrinology & Metabolism examining the latest clinical and preclinical evidence for GLP-1RA-mediated organ protection. The authors synthesize evidence across cardiovascular, renal, hepatic, respiratory, and neurological disease areas, discussing both clinical trial results and mechanistic data.","limitations":"The review notes that while cardiovascular benefits are supported by large outcome trials, evidence for renal, hepatic, respiratory, and neurological protection is at varying stages of maturity. Some organ-protective effects may be primarily mediated by weight loss rather than direct GLP-1 receptor effects. Publication bias may favor positive results in newer application areas. The review doesn't provide a systematic quality assessment of the evidence across disease areas."},{"rthcId":"RPEP-10615","title":"Achieving Over 30% Body Weight Loss With Semaglutide in a Patient: A Case Report.","authors":"Danish, Sidra; Dogra, Vallabh; Rauf, Uzma; Saghir, Maryam; Aslam, Nadia","year":2025,"journal":"Cureus, 17(2), e79254","doi":"10.7759/cureus.79254","pmid":"40125230","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A 69-year-old female with morbid obesity (starting BMI 47, weight 241 lb) lost 90 lb (over 30% of body weight) over 65 weeks of semaglutide treatment. This weight loss exceeded the average reduction reported in previous large-scale studies. The patient experienced no side effects. Additionally, her hypertension resolved and her glucose levels normalized during treatment.","whyItMatters":"Large clinical trials like STEP have shown semaglutide produces average weight loss of about 15-17% of body weight. This case demonstrates that some individuals can achieve dramatically greater results — over 30% — suggesting there may be subpopulations of 'super-responders' to GLP-1 receptor agonist peptide therapy. Understanding why some patients respond so well could help personalize obesity treatment.","specificNumbers":"","methodology":"This is a single-patient case report documenting the clinical outcomes of semaglutide treatment in a 69-year-old woman with morbid obesity and hypertension. Weight, blood pressure, and glucose levels were monitored over the 65-week treatment period. The specific semaglutide formulation and dosing details were not provided in the abstract.","limitations":"As a single-patient case report, this represents the lowest level of clinical evidence. The results cannot be generalized to other patients. The specific semaglutide dose and titration schedule are not detailed in the abstract. No information is provided about diet, exercise, or other lifestyle changes that may have contributed to the outcome. There is no long-term follow-up data on weight maintenance after achieving this loss."},{"rthcId":"RPEP-10616","title":"Potential inhibitors of metalloproteinases (MMPs) and phospholipases from Nemopilema nomurai jellyfish peptides: An in-silico pharmacokinetics and molecular docking studies.","authors":"Danso, Blessing; Fengling, Yang; Hua, Xiaoyu; Zhang, Jinyu; Chen, Jingbo; Yao, Yuan; Pozzolini, Marina; Wang, Fei; Xiao, Liang; Ruixue, Huang","year":2025,"journal":"Toxicon : official journal of the International Society on Toxinology, 263, 108421","doi":"10.1016/j.toxicon.2025.108421","pmid":"40412464","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10617","title":"Mechanistic Insights Into Postprandial Insulin-Glucagon Interactions and Their Impact on Glucose Flux After Protein-Glucose Coingestion in Humans.","authors":"Dao, Giang M; Shaw, Chistopher S; Betik, Andrew C; Kuriel, Vicky; Bruce, Clinton R; Kowalski, Greg M","year":2025,"journal":"Diabetes, 74(11), 1946-1956","doi":"10.2337/db25-0395","pmid":"40928846","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 11 healthy adults, whey protein-glucose coingestion (25WG) produced the lowest glucose excursions compared to glucose alone (25G or 50G). Key peptide hormone responses: glucagon increased ~3-fold with 25WG (suppressed with glucose alone), GIP was significantly higher with 25WG versus both 25G and 50G, GLP-1 was similar across conditions, and insulin was higher for 25WG versus 25G.\n\nCritically, despite greater insulin secretion, whole-body glucose disposal (Rd) was not enhanced. Endogenous glucose production was less suppressed with 25WG (~50%) versus 25G (~70%) or 50G (~80%). The net glycemic benefit stemmed from reduced early-phase (30-60 min) glucose absorption from the gut — a novel mechanistic finding.","whyItMatters":"This study resolves a long-standing paradox in nutrition science: why does protein improve blood sugar control despite stimulating glucagon? The answer — reduced glucose absorption rather than increased glucose uptake — has practical implications for dietary strategies in diabetes management and challenges assumptions about how protein and incretin peptides regulate postprandial glucose.","specificNumbers":"","methodology":"Eleven healthy adults completed three crossover trials ingesting: 25g glucose (25G), 50g glucose (50G), or 25g glucose plus 25g whey protein (25WG). The triple stable isotope glucose tracer technique was used to simultaneously measure glucose absorption from the gut, endogenous glucose production, and whole-body glucose disposal. Blood samples measured insulin, glucagon, GLP-1, and GIP responses.","limitations":"Small sample size (n=11). Only healthy young adults were studied — results may differ in people with type 2 diabetes or impaired glucose tolerance. Only whey protein was tested; other protein sources may behave differently. The triple tracer technique measures net fluxes and may miss tissue-specific effects. A single protein dose (25g) was used, so dose-response relationships are unknown."},{"rthcId":"RPEP-10618","title":"Very-low-calorie-diet, tirzepatide, and bariatric surgery: a multidisciplinary success in super-super obesity.","authors":"Daou, Carla; Barajas-Gamboa, Juan S; Salloum, Cynthia; Guerron, Alfredo Daniel","year":2025,"journal":"Journal of surgical case reports, 2025(4), rjae816","doi":"10.1093/jscr/rjae816","pmid":"40161879","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10619","title":"Successful Ultrasound-Guided Dry Needling for Treatment of Piriformis Syndrome.","authors":"Darmawan, Guntur; Bin Mat Arshad, Anwar Samhari; Wibowo, Suryo Anggoro Kusumo","year":2025,"journal":"Acta medica Indonesiana, 57(2), 273-274","doi":null,"pmid":"40641196","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10620","title":"Surfactant-like peptide gels are based on cross-β amyloid fibrils.","authors":"Das, Abhinaba; Gnewou, Ordy; Zuo, Xiaobing; Wang, Fengbin; Conticello, Vincent P","year":2025,"journal":"Faraday discussions, 260(0), 35-54","doi":"10.1039/d4fd00190g","pmid":"40376775","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Two bola-amphiphilic peptides, L2 (Ac-KLIIIK-NH₂) and L5 (Ac-KIIILK-NH₂), which differ only in the position of a single leucine residue, form morphologically distinct nanostructures — nanosheets and nanotubes, respectively. Cryo-EM helical reconstruction of the L5 nanotube at near-atomic resolution revealed steric zipper interfaces characteristic of cross-β amyloid fibrils, rather than the simple amphiphilic packing previously assumed. Like amyloid structures, these assemblies were highly sensitive to conservative amino acid substitutions, meaning tiny sequence changes dramatically altered the resulting nanostructure.","whyItMatters":"Peptide hydrogels are being developed for wound healing, drug delivery, tissue engineering, and 3D cell culture. Understanding how these peptides actually organize at the molecular level is critical for rationally designing materials with specific properties. The discovery that they use amyloid-like packing — not simple soap-like assembly — fundamentally changes the design rules for engineering peptide-based biomaterials.","specificNumbers":"","methodology":"Researchers synthesized two short peptides (L2 and L5) and characterized their self-assembled structures using cryo-electron microscopy (cryo-EM) with helical reconstruction to achieve near-atomic resolution of the L5 nanotube. They also used small-angle X-ray scattering and other biophysical techniques to compare the structural organization to both conventional amphiphilic assemblies and amyloid fibrils.","limitations":"The study examined only two short peptide sequences, so it remains unclear how broadly these findings apply to the wider family of surfactant-like peptides. The near-atomic structure was determined only for the L5 nanotube; the L2 nanosheet structure was not resolved at the same level of detail. No biological or biocompatibility testing was included — this is purely a structural study."},{"rthcId":"RPEP-10621","title":"Substituent-based Modulation of Self-Assembly and Immunogenicity of Amphipathic Peptides.","authors":"Das, Anirban; Pramanik, Ushasi; Brown, Elise M; Liu, Chih-Yun; Gong, Huan; Fascetti, Jonathan; Gibson, Mark; Stealey, Samuel; Zustiak, Silviya P; Berkland, Cory; Jackrel, Meredith E; White, Mark A; Rudra, Jai S","year":2025,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2025.07.08.663637","pmid":"40672160","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Systematic modification of substituents on benzyl groups attached to short amphipathic peptides produced measurable changes in fibril formation, molecular packing, and immune responses.\n\nBoth the position and the electronic nature (electron-donating vs. withdrawing) of substituents at the para-position of benzyl rings, as well as the chain length connecting the backbone to the aromatic moiety, influenced self-assembly behavior and immunogenicity. The effects were observed both in vitro and in vivo, demonstrating that principles from organic chemistry substituent effects translate directly to peptide nanomaterial design.","whyItMatters":"Peptide-based nanomaterials are being developed for vaccine delivery, tissue engineering, and regenerative medicine, but controlling their properties has been challenging. This study shows that borrowing established principles from organic chemistry — the use of substituent effects — provides a rational and predictable way to tune both the physical structure and biological activity of peptide assemblies, potentially accelerating their translation into clinical applications.","specificNumbers":"","methodology":"Researchers synthesized a series of short amphipathic peptides with systematic chemical modifications at the aromatic side chain positions. They characterized self-assembly behavior, fibril morphology, and molecular packing using biophysical techniques. Immunogenicity was assessed both in cell-based (in vitro) assays and in animal models (in vivo) to determine how chemical modifications affected immune responses to the peptide nanostructures.","limitations":"This is a preprint (bioRxiv) that has not yet undergone peer review. Specific quantitative data on the magnitude of immunogenicity changes are not provided in the abstract. The study focuses on a specific class of short amphipathic peptides, and findings may not generalize to all peptide self-assembly systems. Long-term biocompatibility and clinical translation remain to be evaluated."},{"rthcId":"RPEP-10622","title":"Effect of Oral Semaglutide on Volumetric BMD and Bone Microarchitecture in Overweight/Obese Individuals with Type 2 Diabetes.","authors":"Das, Liza; Bhadada, Sanjay Kumar; Arjunan, Durairaj; Duseja, Ajay","year":2025,"journal":"Calcified tissue international, 116(1), 105","doi":"10.1007/s00223-025-01417-2","pmid":"40782266","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10623","title":"Systematic Determination of the Impact of Structural Edits on Peptide Accumulation into Mycobacteria.","authors":"Dash, Rachita; Liu, Zichen; Lepori, Irene; Chordia, Mahendra D; Ocius, Karl; Holsinger, Kadie; Zhang, Han; Kenyon, Ryan; Im, Wonpil; Siegrist, M Sloan; Pires, Marcos M","year":2025,"journal":"ACS chemical biology, 20(8), 1962-1979","doi":"10.1021/acschembio.5c00330","pmid":"40748788","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10624","title":"Development of polylactic acid microneedles for enhanced transdermal delivery of desmopressin peptides: A computational study.","authors":"Dashti, Amirhossein; Salimibani, Milad; Fanaei, Yegane","year":2025,"journal":"Journal of pharmaceutical sciences, 114(6), 103777","doi":"10.1016/j.xphs.2025.103777","pmid":"40187737","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10625","title":"Peptide-functionalized nanomaterials for controlled drug delivery and regenerative therapies in retinal diseases.","authors":"Dashti, Razieh; Safaei, Fariba; Sadeghian, Golfam; Hosseini, Seyyed Abed; Salimibani, Milad","year":2025,"journal":"Journal of biomaterials applications, 8853282251395196","doi":"10.1177/08853282251395196","pmid":"41187450","tags":[],"studyType":"review","evidenceStrength":"low","keyFinding":"This review examines how peptide-functionalized nanoparticles and nanoscaffolds are being developed to treat degenerative retinal diseases like diabetic retinopathy, age-related macular degeneration (AMD), and retinitis pigmentosa. Key approaches include RGD-modified nanoparticles for receptor-mediated targeting of retinal cells, self-assembling peptide hydrogels that mimic the extracellular matrix to support retinal regeneration, and PEGylated nanostructures that cross the blood-retinal barrier while avoiding immune reactions. Preclinical animal studies have shown promising results for targeted drug delivery, neuroprotection, and stem cell-based regeneration, but scalability, long-term safety, and non-invasive delivery methods remain major challenges.","whyItMatters":"Degenerative retinal diseases are among the leading causes of irreversible blindness worldwide. Current treatments — like anti-VEGF injections for AMD — require repeated invasive eye injections and can only slow disease progression, not restore lost vision. Peptide-functionalized nanomaterials could overcome this by enabling precisely targeted drug delivery across the blood-retinal barrier, controlled release of therapeutics, and scaffolds that guide retinal cell regeneration. This represents a potential shift from managing vision loss to actually restoring it.","specificNumbers":"3 major retinal diseases discussed (diabetic retinopathy, AMD, retinitis pigmentosa) · Multiple peptide-NP platforms reviewed","methodology":"This is a narrative review examining the chemical design, synthesis, and biomedical applications of peptide-functionalized nanomaterials for retinal diseases. It covers biodegradable polymeric nanoparticles, liposomes, hybrid nanostructures, and self-assembling peptide hydrogels, reviewing their drug delivery mechanisms, cellular interactions, immune modulation properties, and preclinical efficacy data.","limitations":"As a review, this article synthesizes existing preclinical research rather than presenting new data. Most evidence comes from animal models with no clinical trials yet conducted for many of the described platforms. Key challenges acknowledged include scalability of manufacturing, long-term safety concerns, and the difficulty of achieving non-invasive delivery to the retina. The review does not systematically assess the quality of the preclinical studies it covers."},{"rthcId":"RPEP-10626","title":"Corneal sensory nerve loss induced by repeated subconjunctival and topical bupivacaine disrupts tear secretion and enhances bacterial adhesion via neuropeptide modulation.","authors":"Datta, Ananya; Orallo, Grace Kelly; Nelson, Nahomy","year":2025,"journal":"PloS one, 20(8), e0329112","doi":"10.1371/journal.pone.0329112","pmid":"40758689","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10627","title":"Efficacy of Semaglutide in Pediatric Patients With Bardet-Biedl Syndrome and Alström Syndrome.","authors":"Dauleh, Hajar; Mohammed, Idris; Hussain, Khalid","year":2025,"journal":"JCEM case reports, 3(12), luaf266","doi":"10.1210/jcemcr/luaf266","pmid":"41312179","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10628","title":"Application of mechanochemistry to green, scalable, and continuous manufacturing of pharmaceutically relevant peptides by twin-screw extrusion.","authors":"Daurio, Dominick; Jacobsen, Casey S; Nagapudi, Karthik; Saw, Robert; Silva Elipe, Maria Victoria; Thiel, Oliver; Balgley, Renata; Chamarthy, Sai Prasanth; Alvarez-Nunez, Fernando","year":2025,"journal":"Journal of pharmaceutical sciences, 114(12), 103941","doi":"10.1016/j.xphs.2025.103941","pmid":"40782893","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10629","title":"Future applications of cyclic antimicrobial peptides in drug delivery.","authors":"Davani-Davari, Dorna; Tiwari, Rakesh Kumar; Parang, Keykavous","year":2025,"journal":"Expert opinion on drug delivery, 22(3), 383-404","doi":"10.1080/17425247.2025.2460661","pmid":"39876578","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10630","title":"The role of vasopressin deficiency in the fluid intake suppression hyper-responsivity to central glucagon-like peptide-1 in the Brattleboro rat.","authors":"David, Sydney A; Brakey, Destiny J; Paul, Matthew J; Daniels, Derek","year":2025,"journal":"Physiology & behavior, 298, 114958","doi":"10.1016/j.physbeh.2025.114958","pmid":"40409558","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10631","title":"Omega-3 Polyunsaturated Fatty Acids (PUFAs) and Diabetic Peripheral Neuropathy: A Pre-Clinical Study Examining the Effect of Omega-3 PUFAs from Fish Oil, Krill Oil, Algae or Pharmaceutical-Derived Ethyl Esters Using Type 2 Diabetic Rats.","authors":"Davidson, Eric; Obrosov, Oleksandr; Coppey, Lawrence; Yorek, Mark","year":2025,"journal":"Biomedicines, 13(7)","doi":"10.3390/biomedicines13071607","pmid":"40722680","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10632","title":"Use of tirzepatide (Mounjaro) in type 2 diabetes management: an overview.","authors":"Davies, Claire","year":2025,"journal":"Nursing standard (Royal College of Nursing (Great Britain) : 1987), 40(7), 47-53","doi":"10.7748/ns.2025.e12464","pmid":"40383978","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10633","title":"Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes.","authors":"Davies, Melanie J; Bajaj, Harpreet S; Broholm, Christa; Eliasen, Astrid; Garvey, W Timothy; le Roux, Carel W; Lingvay, Ildiko; Lyndgaard, Christian Bøge; Rosenstock, Julio; Pedersen, Sue D","year":2025,"journal":"The New England journal of medicine, 393(7), 648-659","doi":"10.1056/NEJMoa2502082","pmid":"40544432","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10634","title":"Semaglutide in obesity-related heart failure with preserved ejection fraction and type 2 diabetes across baseline HbA1c levels (STEP-HFpEF DM): a prespecified analysis of heart failure and metabolic outcomes from a randomised, placebo-controlled trial.","authors":"Davies, Melanie J; van der Meer, Peter; Verma, Subodh; Patel, Shachi; Chinnakondepalli, Khaja M; Borlaug, Barry A; Butler, Javed; Kitzman, Dalane W; Shah, Sanjiv J; Harring, Signe; Salsali, Afshin; Rasmussen, Søren; von Lewinski, Dirk; Abhayaratna, Walter; Petrie, Mark C; Kosiborod, Mikhail N","year":2025,"journal":"The lancet. Diabetes & endocrinology, 13(3), 196-209","doi":"10.1016/S2213-8587(24)00304-8","pmid":"39848268","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10635","title":"Glucagon-Like Peptide-1 Receptor Agonists in Plastic Surgery: Perioperative Considerations and Safety Protocols.","authors":"Davila Diaz, Rodrigo; Campos Barrera, Eugenia; Diaz Fosado, Luis Alfonso; Reyes Esparza, Arturo; Perez Benitez, Omar A","year":2025,"journal":"Cureus, 17(12), e99865","doi":"10.7759/cureus.99865","pmid":"41445996","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10636","title":"Proteolytic stabilization of a spider venom peptide results in an orally active bioinsecticide.","authors":"Davis, Breck R; Haase, Alexandra M; Tourtois, Joseph S; Hulbert, Daniel L; Cornell, Rachel E; DeVree, Brian T; Flohrschutz, Cadence J; Bell, Lucille M; Peck, Daniel C; Nguyen, Trang T; Bao, Lin; Kennedy, Robert M; Schneider, Kyle D","year":2025,"journal":"Pest management science, 81(10), 6404-6415","doi":"10.1002/ps.8980","pmid":"40534215","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10637","title":"Severe Hypomagnesemia and Hypocalcemia Linked to Semaglutide in Type 2 Diabetes: A Case Report.","authors":"Davis, Timothy Mark Earls","year":2025,"journal":"The American journal of case reports, 26, e946539","doi":"10.12659/AJCR.946539","pmid":"39757501","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10638","title":"Chemoselective, regioselective, and positionally selective fluorogenic stapling of unprotected peptides for cellular uptake and direct cell imaging.","authors":"Dayanara, Naysilla L; Froelich, Juliette; Roome, Pascale; Perrin, David M","year":2025,"journal":"Chemical science, 16(2), 584-595","doi":"10.1039/d4sc04839c","pmid":"39620082","tags":[],"studyType":"in vitro","evidenceStrength":"low","keyFinding":"Researchers developed a new method for \"stapling\" peptides — chemically locking them into their active helical shape — that works on unprotected peptides using natural amino acid residues (lysine and cysteine). The technique, called FlICk (Fluorescent Isoindole Crosslink), uses a three-component reaction that is rapid, mild, and highly selective. A key bonus: the staple itself is fluorescent, emitting blue-green light that allows researchers to directly image the peptide inside cells without needing to attach a separate fluorescent tag. A FlICk-stapled peptide showed cytotoxicity with an IC50 of 5.10 μM, matching the potency of a conventional olefin-stapled version.","whyItMatters":"Many important drug targets involve protein-protein interactions — large, flat surfaces that are notoriously difficult to block with small molecules. Stapled peptides can disrupt these interactions by mimicking the helical shape of natural protein partners. However, current stapling methods often require non-natural amino acids or complex protection chemistry. This new approach works with natural amino acids on unprotected peptides and produces a built-in fluorescent reporter, simplifying both the synthesis and the evaluation of stapled peptide drugs.","specificNumbers":"IC50 = 5.10 ± 1.27 μM for FlICk-stapled peptide · i, i+4 positional selectivity · Lysine-cysteine crosslink","methodology":"The researchers synthesized stapled peptides using 2-arylketobenzaldehydes (ArKBCHOs) as molecular linchpins in a three-component reaction with lysine and cysteine residues on unprotected peptides. They characterized the selectivity (chemo-, regio-, and positional) of the stapling reaction, measured in vitro cytotoxicity of the stapled peptides, and leveraged the inherent fluorescence of the thiol-isoindole crosslink for cellular imaging to assess cell permeability.","limitations":"This is early-stage chemistry research with only in vitro validation. Cytotoxicity was demonstrated for one peptide target, and it's unclear how broadly the technique applies across different peptide sequences. Cell permeability was assessed via imaging but not quantified with uptake assays. No in vivo studies or pharmacokinetic data were presented. The long-term stability of the fluorescent staple in biological environments is not addressed."},{"rthcId":"RPEP-10639","title":"Comprehensive Access to Semaglutide: Clinical and Economic Implications for Medicare.","authors":"Dayer, Victoria W; Nourhussein, Iman; Kasle, Adam; Hansen, Ryan N; Navas, Angelo; Sullivan, Sean D","year":2025,"journal":"Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research, 28(10), 1488-1496","doi":"10.1016/j.jval.2025.07.007","pmid":"40701338","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10640","title":"Peptides from Animal Venoms: A Promising Frontier in Diabetes Therapy via Multi-Target Mechanisms.","authors":"de Almeida, José Otávio Carvalho Sena; Comerma-Steffensen, Simón Gabriel; de Souza de Almeida Leite, José Roberto; Simonsen, Ulf; Arcanjo, Daniel Dias Rufino","year":2025,"journal":"Pharmaceuticals (Basel, Switzerland), 18(10)","doi":"10.3390/ph18101438","pmid":"41155553","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10641","title":"Is peptide receptor radionuclide therapy still a promising option for medullary thyroid carcinoma?","authors":"de Andrade, Fernanda Accioly; Bulzico, Daniel; Corbo, Rossana; Vaisman, Fernanda","year":2025,"journal":"Endocrine, 87(3), 943-950","doi":"10.1007/s12020-024-04114-6","pmid":"39609369","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Peptide receptor radionuclide therapy (PRRT) remains a potential treatment option for medullary thyroid carcinoma, particularly for patients with RET-negative recurrent or metastatic disease who have limited systemic therapy options. However, its clinical utility in the RET inhibitor era is uncertain. Highly selective RET inhibitors have proven efficacy with low toxicity for RET-mutated MTC, and multikinase inhibitors are available but limited by resistance and side effects. PRRT's role is now most relevant for the subset of patients who cannot benefit from RET-targeted therapy.","whyItMatters":"Medullary thyroid carcinoma patients without RET mutations face a difficult treatment landscape — multikinase inhibitors often cause significant side effects or stop working due to resistance. PRRT, which uses radiolabeled peptides to deliver targeted radiation directly to tumor cells via peptide receptors, could fill an important niche for these underserved patients if its efficacy can be better established.","specificNumbers":"","methodology":"Narrative review evaluating the published evidence on peptide receptor radionuclide therapy in medullary thyroid carcinoma, including discussion of its limitations in the context of newly approved RET inhibitors and existing multikinase inhibitor therapies.","limitations":"As a narrative review, the article does not apply systematic search methodology or meta-analysis. The evidence base for PRRT in MTC specifically is limited, with small case series rather than large randomized trials. The abstract does not report specific response rates or survival data for PRRT in MTC. The review acknowledges that PRRT's clinical utility 'remains under investigation.'"},{"rthcId":"RPEP-10642","title":"Clinical Outcomes Associated with the Use of a Family-Based Digital Support Program in Patients with Pharmacologic Treatment for Obesity.","authors":"de Arriba Muñoz, Antonio; Rodríguez-Montes, Oscar Eduardo; Conde-Moro, Ana Rocío; Garcia Castellanos, María Teresa; Martínez García, José Andrés; Fernández-Luque, Luis","year":2025,"journal":"Journal of clinical medicine, 15(1)","doi":"10.3390/jcm15010222","pmid":"41517470","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10643","title":"Post Hoc Analysis of SURPASS-1 to -5: Efficacy and Safety of Tirzepatide in Adults with Type 2 Diabetes are Independent of Baseline Characteristics.","authors":"De Block, Christophe; Peleshok, Jennifer; Wilding, John P H; Kwan, Anita Y M; Rasouli, Neda; Maldonado, Juan M; Wysham, Carol; Liu, Minzhi; Aleppo, Grazia; Benneyworth, Brian D","year":2025,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 16(1), 43-71","doi":"10.1007/s13300-024-01660-0","pmid":"39531161","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10644","title":"A Combined GLP-1/PPARa/CB1-Based Therapy to Restore the Central and Peripheral Metabolic Dysregulation Induced by a High-Fructose High-Fat Diet.","authors":"de Ceglia, Marialuisa; Rasheed, Nabila; Tovar, Rubén; Pareja-Cerbán, Inés; Arias-Sáez, Andrea; Gavito, Ana; Gaetani, Silvana; Cifani, Carlo; Rodríguez de Fonseca, Fernando; Decara, Juan","year":2025,"journal":"International journal of molecular sciences, 26(6)","doi":"10.3390/ijms26062420","pmid":"40141063","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10645","title":"Design of Natterins-based peptides improves antimicrobial and antiviral activities.","authors":"de Cena, Gabrielle L; Tada, Dayane B; Lucchi, Danilo B M; Santos, Tiago A A; Heras, Montserrat; Juliano, Maria; Torres Braconi, Carla; Castanho, Miguel A R B; Lopes-Ferreira, Mônica; Conceição, Katia","year":2025,"journal":"Biotechnology reports (Amsterdam, Netherlands), 45, e00867","doi":"10.1016/j.btre.2024.e00867","pmid":"39758971","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10646","title":"Persistence, effectiveness, and tolerability of anti-calcitonin gene-related peptide monoclonal antibodies in patients with chronic migraine.","authors":"de Dios, Anna; Pagès-Puigdemont, Neus; Ojeda, Sergio; Riera, Pau; Pelegrín, Rebeca; Morollon, Noemí; Belvís, Robert; Real, Jordi; Masip, Montserrat","year":2025,"journal":"Headache, 65(1), 24-34","doi":"10.1111/head.14827","pmid":"39268992","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10647","title":"The Sweet Side of Constipation: Colonic Motor Dysfunction in Diabetes Mellitus.","authors":"De Fano, Michelantonio; Baluganti, Sara; Manco, Marcello; Porcellati, Francesca; Fanelli, Carmine G; Bassotti, Gabrio","year":2025,"journal":"Nutrients, 17(19)","doi":"10.3390/nu17193038","pmid":"41097116","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Constipation in diabetes has a multifactorial etiology involving structural changes in gastrointestinal tract wall tissues and functional abnormalities secondary to chronic hyperglycemia. GLP-1 receptor agonists — peptide-based medications critical for glycemic control and cardiovascular/renal risk reduction in type 2 diabetes — are identified as an additional cause of constipation.\n\nDiagnosis is typically clinical, as validated methods for assessing colonic transit are invasive and limited to specialized centers. Treatment follows a stepwise approach: dietary modification and physical activity first, followed by laxatives, and finally newer agents or mechanical methods for refractory cases.","whyItMatters":"GLP-1 receptor agonists are among the fastest-growing drug classes worldwide, with tens of millions of prescriptions annually for diabetes and obesity. As these peptide drugs become standard of care, their gastrointestinal side effects — particularly constipation — deserve more clinical attention. Understanding that constipation in diabetic patients may be disease-related, drug-related, or both is essential for proper management and quality of life.","specificNumbers":"","methodology":"This is a narrative review of literature published up to May 30, 2025, focusing on the pathogenesis of constipation in diabetes mellitus, the correlation with GLP-1 receptor agonist treatment, and the diagnostic-therapeutic framework.","limitations":"As a narrative review, it may not capture all relevant literature systematically. The abstract does not provide prevalence estimates for constipation in GLP-1 RA users specifically. The multifactorial nature of constipation in diabetes makes it difficult to attribute causation to any single factor. The review does not compare constipation rates across different GLP-1 agonists or doses."},{"rthcId":"RPEP-10648","title":"Impact of glucagon-like peptide-1 receptor agonists on alcohol consumption and liver-related outcomes: A systematic review and meta-analysis.","authors":"de Faria Moraes, Bernardo; André Pedral Diniz Leite, Gabriel; André Pedral Diniz Leite, Gustavo; Silveira, Igor Boechat; Lana, Nathália Veloso; Cançado, Guilherme Grossi Lopes","year":2025,"journal":"Drug and alcohol dependence, 275, 112840","doi":"10.1016/j.drugalcdep.2025.112840","pmid":"40845737","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10649","title":"Detection of Bioactive Peptides' Signature in Podolica Cow's Milk.","authors":"De Fazio, Rosario; Di Francesco, Antonella; Di Ciccio, Pierluigi Aldo; Cunsolo, Vincenzo; Britti, Domenico; Lomagistro, Carmine; Roncada, Paola; Piras, Cristian","year":2025,"journal":"Foods (Basel, Switzerland), 14(5)","doi":"10.3390/foods14050877","pmid":"40077579","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Using top-down peptidomics on milk samples from four farms, the researchers identified 2,213 peptides total, with 19 matching known bioactive sequences. Key bioactivities included DPP-IV inhibition (relevant to type 2 diabetes management), ACE inhibition (relevant to blood pressure control), antioxidant activity, enhanced calcium uptake, and antimicrobial effects.\n\nSpecific DPP-IV-inhibitory peptides such as LDQWLCEKL and VGINYWLAHK were identified, along with ACE-inhibitory peptides YLGY and FFVAPFPEVFGK. Antimicrobial peptides SDIPNPIGSENSEK and VLNENLLR showed broad-spectrum activity against harmful microorganisms. Additional peptides with osteoanabolic, antianxiety, and immunomodulatory properties were also detected.","whyItMatters":"Food-derived bioactive peptides are increasingly recognized as potential natural alternatives or supplements for managing chronic conditions like diabetes and hypertension. Characterizing the peptide profile of specific milk types like Podolica could support the development of functional dairy products and add economic value to traditional farming practices while providing scientifically grounded health claims.","specificNumbers":"","methodology":"Milk samples were collected from Podolica cows on four different farms in southern Italy. The researchers used top-down peptidomics — a technique that analyzes intact peptides rather than breaking them down first — to identify and characterize the peptide profile. Identified peptides were then matched against databases of known bioactive sequences to determine potential health-related activities.","limitations":"This is a discovery-phase study that identified peptides based on sequence matching to known bioactive databases. No functional assays were conducted to confirm the bioactivities of these specific peptides from Podolica milk. The peptides were identified in raw milk, and it is unknown whether they survive pasteurization, digestion, and absorption. Only four farms were sampled, and seasonal or dietary variations in peptide content were not assessed."},{"rthcId":"RPEP-10650","title":"Current and Novel Therapies for Cluster Headache: A Narrative Review.","authors":"de Freitas Dias, Bruna; Robinson, Christopher L; Villar-Martinez, Maria Dolores; Ashina, Sait; Goadsby, Peter J","year":2025,"journal":"Pain and therapy, 14(1), 1-19","doi":"10.1007/s40122-024-00674-7","pmid":"39489854","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10651","title":"Glucagon-like peptide-1 receptor agonists for major neurocognitive disorders.","authors":"De Giorgi, Riccardo; Ghenciulescu, Ana; Yotter, Courtney; Taquet, Maxime; Koychev, Ivan","year":2025,"journal":"Journal of neurology, neurosurgery, and psychiatry, 96(9), 870-883","doi":"10.1136/jnnp-2024-335593","pmid":"40210453","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10652","title":"Immunogenicity of Generic Peptide Impurities: Current Orthogonal Approaches.","authors":"De Groot, Anne S; Mattei, Aimee; Gabriel, Benjamin; Calderini, Jennifer; Roberts, Brian J; Lelias, Sandra; McAllister, Mitchell; Boyle, Christine; Martin, William; Richard, Guilhem","year":2025,"journal":"Pharmaceutical research, 42(5), 805-818","doi":"10.1007/s11095-025-03843-1","pmid":"40126816","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10653","title":"Plasma with Added Protease Inhibitors Improves Alpha- and Beta-CGRP Measurement Compared to Serum: Towards a Reliable Biomarker for Chronic Migraine.","authors":"de la Guerra-Sasián, Lucía; Gárate, Gabriel; Madera, Jorge; Pérez-Pereda, Sara; Pascual-Mato, Marta; González-Quintanilla, Vicente; Pascual, Julio; Muñoz-San Martín, María","year":2025,"journal":"International journal of molecular sciences, 26(20)","doi":"10.3390/ijms26209958","pmid":"41155252","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10654","title":"Incretin-Related Pathology and Serum Exosome Detection in Experimental Alcohol-Related Brain Damage.","authors":"de la Monte, Suzanne M; Tong, Ming; Yang, Yiwen","year":2025,"journal":"Biomolecules, 15(12)","doi":"10.3390/biom15121670","pmid":"41463326","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10655","title":"ANMCO statement: semaglutide in the cardio-nephro-metabolic continuum.","authors":"De Luca, Leonardo; Bilato, Claudio; Navazio, Alessandro; Corda, Marco; Milli, Massimo; Scicchitano, Pietro; Di Marco, Massimo; Riccio, Carmine; Geraci, Giovanna; Iacovoni, Attilio; Pascale, Vittorio; Tizzani, Emanuele; Gabrielli, Domenico; Grimaldi, Massimo; Colivicchi, Furio; Oliva, Fabrizio","year":2025,"journal":"European heart journal supplements : journal of the European Society of Cardiology, 27(Suppl 5), v247-v255","doi":"10.1093/eurheartjsupp/suaf071","pmid":"40385470","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10656","title":"Characterization and Identification of Potential Antioxidant, Antidiabetic, and Antihypertensive Peptides From Hydrolysates of Tenebrio molitor Flour and Its Protein Concentrate.","authors":"de Matos, Francielle Miranda; de Castro, Ruann Janser Soares","year":2025,"journal":"Journal of food science, 90(10), e70595","doi":"10.1111/1750-3841.70595","pmid":"41025494","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10657","title":"High-Sensitivity Cardiac Troponin I for Risk Stratification in Wild-Type Transthyretin Amyloid Cardiomyopathy.","authors":"De Michieli, Laura; Sinigiani, Giulio; Guida, Gianluigi; Saturi, Giulia; Sena, Giuseppe; Capovilla, Teresa Maria; Cantone, Anna; Cianca, Alessandro; Lupi, Alessandro; Porcari, Aldostefano; Tini, Giacomo; Vergaro, Giuseppe; Cappelli, Francesco; Albertini, Riccardo; Bianco, Matteo; Mussinelli, Roberta; Serenelli, Matteo; Musumeci, Beatrice; Perlini, Stefano; Merlo, Marco; Longhi, Simone; Sinagra, Gianfranco; Perazzolo Marra, Martina; Iliceto, Sabino; Jaffe, Allan S; Palladini, Giovanni; Cipriani, Alberto; Milani, Paolo","year":2025,"journal":"Circulation. Heart failure, 18(8), e012816","doi":"10.1161/CIRCHEARTFAILURE.125.012816","pmid":"40371473","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10658","title":"Histamine plasma levels from dietary histidine/histamine intake correlate with CGRP in trigeminal tissues.","authors":"de Mora, Fernando; Dux, Mária; Vogler, Birgit; Kuhn, Annette; Schramm, Jana; Messlinger, Karl","year":2025,"journal":"The journal of headache and pain, 26(1), 258","doi":"10.1186/s10194-025-02178-x","pmid":"41233718","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10659","title":"Orthobiologics and Peptide Therapy for Central Nervous System Repair in Neurodegenerative Conditions.","authors":"de Oliveira, Cézar Augusto Alves; Oliveira, Bernardo Scaldini; Oliveira, Amanda Scaldini; de Souza Loduca, Rafael Duarte; Junior, Carlos Roberto Massella; Santos, Gabriel Silva","year":2025,"journal":"Cells, 14(23)","doi":"10.3390/cells14231853","pmid":"41369342","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10660","title":"Testing antimicrobial peptides inhibiting protein synthesis in living E. coli and K. pneumoniae using bio-orthogonal non-canonical amino-acid tagging.","authors":"de Pascale, Luigi; D'Amore, Agnese; Di Stasi, Adriana; Morici, Martino; Pacor, Sabrina; Tossi, Alessandro; Pham, Thuy Duong; Fabbretti, Attilio; Wilson, Daniel N; Mardirossian, Mario; Scocchi, Marco","year":2025,"journal":"Frontiers in microbiology, 16, 1713216","doi":"10.3389/fmicb.2025.1713216","pmid":"41477210","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10661","title":"Comparative Whole Metagenome Analysis in Lesional and Nonlesional Scalp Areas of Patients with Psoriasis Capitis and Healthy Individuals.","authors":"De Pessemier, Britta; López, Celia Díez; Taelman, Steff; Verdonck, Merel; Chen, Yang; Stockman, Annelies; Lambert, Jo; Van de Wiele, Tom; Callewaert, Chris","year":2025,"journal":"The Journal of investigative dermatology, 145(3), 605-617.e14","doi":"10.1016/j.jid.2024.07.020","pmid":"39128495","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10662","title":"Migraine treatment with CGRP monoclonal antibodies: patient evaluation of a mandatory treatment holiday in Belgium.","authors":"De Praeter, Ruben; Tuerlinckx, Evelien; Schoenen, Jean; Boon, Elizabet; Sava, Simona Liliana; Debruyne, Frederik; Delmotte, Koen; De Pauw, Adinda; Van Dycke, Annelies; Van Humbeeck, Cindy; Versijpt, Jan","year":2025,"journal":"Acta neurologica Belgica, 125(4), 989-998","doi":"10.1007/s13760-025-02782-3","pmid":"40210844","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 243 patients across nine Belgian headache clinics: 86.0% reported worsening migraine during the mandatory 3-month treatment holiday, with 59.4% deteriorating within the first month. Only 3.0% improved and 11.0% experienced no change. For 5.9%, worsening extended beyond the 3-month holiday, delaying treatment resumption.\n\nAnxiety about the holiday was reported by 45.0% of patients, with 18.6% experiencing very high anxiety levels. A significant association was found between anxiety and migraine deterioration (p=0.012). Despite the negative impact, 49.1% found the holiday useful for confirming treatment need, and 22.6% found it very useful.","whyItMatters":"This study provides real-world evidence that mandatory treatment holidays for anti-CGRP antibodies cause significant harm to most patients. As health systems worldwide consider cost-containment measures for expensive biologic therapies, this data shows that rigid interruption policies have real clinical consequences. The findings could influence insurance and regulatory policies in Belgium and other countries considering similar mandates.","specificNumbers":"","methodology":"Prospective multicenter study of 243 patients from nine Belgian headache clinics receiving erenumab, fremanezumab, or galcanezumab. Participants completed a structured questionnaire during their yearly follow-up visit after the treatment holiday, assessing subjective migraine evolution, anxiety levels, and perceived usefulness of the mandatory break.","limitations":"The questionnaire relied on subjective patient reports rather than objective migraine day counts from diaries. The study did not include a control group (patients continuing treatment), so some worsening could reflect natural migraine fluctuation. The association between anxiety and worsening could be bidirectional — anxiety might worsen migraines, or worsening migraines might increase anxiety. Specific anti-CGRP antibody differences were not analyzed separately."},{"rthcId":"RPEP-10663","title":"Eligibility for and practical implications of Semaglutide in overweight and obese patients with acute coronary syndrome.","authors":"De Sio, Vincenzo; Gragnano, Felice; Capolongo, Antonio; Guarnaccia, Natale; Maddaluna, Pasquale; Acerbo, Vincenzo; Galli, Mattia; Berteotti, Martina; Sperlongano, Simona; Cesaro, Arturo; Moscarella, Elisabetta; Pelliccia, Francesco; Patti, Giuseppe; Antonucci, Emilia; Cirillo, Plinio; Pignatelli, Pasquale; Palareti, Gualtiero; Pengo, Vittorio; Gresele, Paolo; Marcucci, Rossella; Calabrò, Paolo","year":2025,"journal":"International journal of cardiology, 423, 133028","doi":"10.1016/j.ijcard.2025.133028","pmid":"39890028","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Of 2,940 consecutive acute coronary syndrome patients in the START-ANTIPLATELET registry, 807 (27.4%) met the SELECT trial eligibility criteria for semaglutide at 60 days post-discharge: age ≥45, BMI ≥27, history of MI/stroke/peripheral artery disease, and no diabetes.\n\nAt one-year follow-up, the SELECT-eligible group had significantly lower rates of major adverse cardiovascular events (MACE: 4.6% vs. 8.2%, p=0.004) and net adverse clinical events (NACE: 3.6% vs. 7.6%, p<0.001) compared to ineligible patients. This paradoxically lower event rate in the eligible group suggests that the SELECT criteria may identify a population with a different risk profile than the broader ACS population.","whyItMatters":"Semaglutide's cardiovascular benefits in the SELECT trial were groundbreaking, but translating trial results into real-world practice requires knowing how many patients qualify. This study shows that over a quarter of heart attack patients could be candidates — a substantial number that could reshape secondary prevention strategies for cardiovascular disease.","specificNumbers":"","methodology":"This was a retrospective analysis of the multicenter START-ANTIPLATELET registry (NCT02219984), which enrolled consecutive ACS patients across Italian centers. Patients were stratified by SELECT trial eligibility criteria at 60 days post-ACS discharge. Outcomes (MACE and NACE composites) were compared between eligible and ineligible groups at 1-year follow-up.","limitations":"This was an observational registry analysis, not a randomized trial, so the outcome differences between groups may reflect confounders rather than treatment effects. The study assessed eligibility only — patients were not actually treated with semaglutide. The registry was Italian, which may limit generalizability to other populations with different obesity and diabetes prevalence rates."},{"rthcId":"RPEP-10664","title":"Lipidized LL37-loaded PLGA nanocarriers: Bioengineered peptide delivery systems for enhanced wound healing.","authors":"De Soricellis, Chiara; Laigle, Chloé; Spinelli, Lucio; Monti, Maria Chiara; Amante, Chiara; Russo, Paola; Aquino, Rita Patrizia; Rousselle, Patricia; Lollo, Giovanna; Del Gaudio, Pasquale","year":2025,"journal":"International journal of pharmaceutics, 677, 125668","doi":"10.1016/j.ijpharm.2025.125668","pmid":"40316190","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Palmitoylated LL37 antimicrobial peptide encapsulated in PLGA nanoparticles showed enhanced stability and controlled release. Microfluidic fabrication produced superior nanoparticles compared to nanoprecipitation — smaller (102.3 nm vs 189.3 nm), more uniform, more stable, and with prolonged peptide release. The loaded nanoparticles enhanced keratinocyte uptake and significantly accelerated fibroblast-mediated wound closure. Proteomic analysis of the nanoparticle protein corona showed enrichment in coagulation, inflammation modulation, and extracellular matrix remodeling proteins.","whyItMatters":"LL37, the only human cathelicidin antimicrobial peptide, is a promising alternative to antibiotics for treating chronic and drug-resistant wound infections. But free LL37 degrades rapidly and is toxic at high concentrations. This nanoparticle delivery system solves both problems — protecting the peptide while releasing it in a controlled manner that accelerates wound healing and fights infection simultaneously.","specificNumbers":"","methodology":"Palmitoylated LL37 was encapsulated in FDA-approved PLGA nanoparticles using two fabrication methods: nanoprecipitation and microfluidics. Nanoparticles were characterized for size, uniformity, stability, and peptide release kinetics. Biological activity was tested through keratinocyte uptake assays and fibroblast wound closure (scratch) assays. Proteomic analysis of the nanoparticle protein corona (proteins that adsorb to the surface in biological fluids) was performed to understand how the nanoparticles interact with the wound environment.","limitations":"All experiments were conducted in vitro using cell cultures — no in vivo animal wound healing studies were performed. The proteomic protein corona analysis suggests the nanoparticles may modulate the wound environment, but this has not been confirmed in living tissue. The antimicrobial activity of the encapsulated LL37 against specific wound pathogens is not reported in the abstract. Scale-up feasibility from microfluidics to manufacturing is not addressed."},{"rthcId":"RPEP-10665","title":"Incretin Receptors in the Peripheral Nervous System: Implications for Obesity Treatment and Peripheral Neuropathy.","authors":"de Sousa, Erica; Sparks, Lauren; Townsend, Kristy","year":2025,"journal":"Diabetes, 74(8), 1313-1319","doi":"10.2337/db25-0158","pmid":"40690614","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10666","title":"Linking clinical and imaging diagnostic assessments of the feline hypertrophic cardiomyopathy phenotype.","authors":"de Sousa, Felipe Gaia; Muzzi, Ruthnea Aparecida Lazaro; de Araújo, Roberto Baracat; Faleiros, Rafael Resende; Queiroz, Fabiana Silva Fádel; Beier, Suzane Lilian","year":2025,"journal":"Frontiers in veterinary science, 12, 1720886","doi":"10.3389/fvets.2025.1720886","pmid":"41487485","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10667","title":"The GLP-1 Analog Liraglutide Reduces Fever Through Sex-Dependent Neuroinflammatory Modulation.","authors":"de Sousa, Gabriela L Soares; da Cruz, Ester K Martins; de Aguiar, Sara C Rojas; Nascimento, Ana P Lima do; Gomes, Bruna R Bezerra; Londe, Anna B Rodrigues; Gonçalves, Luana J Faria; Royer, Carine; Costa, Regina Azevedo; Zampronio, Aleksander Roberto; de Souza, Paulo Eduardo Narcizo; Veiga-Souza, Fabiane H","year":2025,"journal":"Pharmaceuticals (Basel, Switzerland), 18(11)","doi":"10.3390/ph18111738","pmid":"41304982","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10668","title":"The role of dopamine release and D2 dopamine receptor in GHRH and somatostatin cells in controlling growth hormone secretion.","authors":"de Souza, Gabriel O; Gusmao, Daniela O; de Sousa, Maria E; Martins, Marina G; Basso, Alexandre S; Donato, Jose","year":2025,"journal":"Frontiers in endocrinology, 16, 1741139","doi":"10.3389/fendo.2025.1741139","pmid":"41601936","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10669","title":"Efficacy of monoclonal antibodies against CGRP in migraine patients with fibromyalgia comorbidity: a retrospective monocentric observational study.","authors":"de Tommaso, Marina; Scannicchio, Stefania; Paparella, Giulia; Clemente, Livio; Libro, Giuseppe","year":2025,"journal":"The journal of headache and pain, 26(1), 102","doi":"10.1186/s10194-025-02034-y","pmid":"40329175","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10670","title":"Feeding state-dependent neuropeptidergic modulation of reciprocally interconnected inhibitory neurons biases sensorimotor decisions in Drosophila.","authors":"de Tredern, Eloïse; Manceau, Dylan; Blanc, Alexandre; Parameswaran, Abhijit; Sakagiannis, Panagiotis; Barre, Chloe; Sus, Victoria; Viscido, Francesca; Akiki, Perla; Hasan, Md Amit; Autran, Sandra; Laurent, François; Nawrot, Martin Paul; Masson, Jean-Baptiste; Jovanic, Tihana","year":2025,"journal":"Nature communications, 16(1), 8198","doi":"10.1038/s41467-025-61805-y","pmid":"40897720","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10671","title":"Biophysical investigations of the membrane interactions of collagen VI-derived host defense peptides.","authors":"De, Kathakali; Bryder, Karin; Aisenbrey, Christopher; Mörgelin, Matthias; Bechinger, Burkhard","year":2025,"journal":"Biochimica et biophysica acta. Biomembranes, 1867(8), 184448","doi":"10.1016/j.bbamem.2025.184448","pmid":"40885328","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10672","title":"Mechanism of Action and Membrane Interactions of Antibacterial Quaternized Triazolium Peptoids.","authors":"De, Kathakali; Guerinot, Cassandra; Charbonnel, Nicolas; Faure, Allison; Josse, Jérôme; Aisenbrey, Christopher; Faure, Sophie; Bechinger, Burkhard","year":2025,"journal":"Journal of medicinal chemistry, 68(24), 26206-26217","doi":"10.1021/acs.jmedchem.5c02254","pmid":"41396478","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Eight triazolium-based peptoids with polyproline I (PPI) helical structures were tested against bacterial and eukaryotic membrane models. Calcein leakage experiments (measuring membrane disruption) showed excellent correlation with both antibacterial activity against Gram-positive and Gram-negative bacteria and selectivity (low toxicity to human red blood cells).\n\nCD spectroscopy confirmed the designed PPI helical fold. Fluorescence assays quantitatively measured membrane association and showed the peptoids localize at the membrane interface. Solid-state NMR spectroscopy revealed significant reduction in lipid order parameters in the presence of peptoids, indicating membrane destabilization. These converging biophysical findings establish that the peptoids share the membrane-mediated mechanism of action of their natural antimicrobial peptide templates.","whyItMatters":"Understanding how peptoid antibiotics work at the molecular level is essential for rational design of next-generation antimicrobials. This study's demonstration that peptoid-membrane interactions directly predict antibacterial activity means researchers can now use relatively quick biophysical assays to screen and optimize peptoid candidates before expensive biological testing. The membrane-disruption mechanism also suggests peptoids may share the natural resistance-evading properties of antimicrobial peptides — bacteria struggle to develop resistance against agents that attack their fundamental membrane structure.","specificNumbers":"","methodology":"Eight peptoids with quaternized triazolium groups were synthesized and characterized. Their interactions with lipid bilayers modeling bacterial membranes (anionic) and eukaryotic membranes (zwitterionic) were studied using calcein leakage (membrane permeabilization), circular dichroism (CD) spectroscopy (secondary structure), fluorescence assays (membrane binding and localization), and solid-state NMR spectroscopy (lipid order parameter changes). Antibacterial activity was tested against Gram-positive and Gram-negative bacteria, and hemolytic activity was assessed using human red blood cells.","limitations":"The study used model lipid bilayers rather than whole bacterial cells for most biophysical experiments, which may not fully capture the complexity of real bacterial membranes (which contain proteins, lipopolysaccharides, and peptidoglycan). In vivo efficacy and pharmacokinetics were not assessed. The correlation between membrane activity and antibacterial activity, while excellent, was established with a limited set of eight peptoids. Long-term resistance development was not studied. Selectivity between bacterial and mammalian membranes, while demonstrated via hemolysis assays, was not tested in more complex mammalian cell models."},{"rthcId":"RPEP-10673","title":"Semaglutide and cardiovascular outcomes by baseline and changes in adiposity measurements: a prespecified analysis of the SELECT trial.","authors":"Deanfield, John; Lincoff, A Michael; Kahn, Steven E; Emerson, Scott S; Lingvay, Ildiko; Scirica, Benjamin M; Plutzky, Jorge; Kushner, Robert F; Colhoun, Helen M; Hovingh, G Kees; Stensen, Signe; Weeke, Peter E; Jeppesen, Ole Kleist; Bravo, Rafael; Wu, Chau-Chung; Komuro, Issei; Santini, Ferruccio; Hjelmesæth, Jøran; Urina-Triana, Miguel; Buscemi, Silvio; Ryan, Donna H","year":2025,"journal":"Lancet (London, England), 406(10516), 2257-2268","doi":"10.1016/S0140-6736(25)01375-3","pmid":"41138739","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10674","title":"Incretin receptor agonism during pregnancy: implications for mother and baby.","authors":"Dearden, Laura; Ozanne, Susan E","year":2025,"journal":"Clinical science (London, England : 1979), 139(23), 1597-610","doi":"10.1042/CS20258493","pmid":"41359794","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10675","title":"Self-Assembling Nucleopeptides Exhibiting Strong Antimicrobial Activity against Multidrug-Resistant Clinically Isolated Strains and In Vitro Wound Healing Compatibility.","authors":"Deb, Swapnendu; Gupta, Shalini; Bose, Supratim; Mondal, Tanushree; Mondal, Biplab; Banerjee, Arindam","year":2025,"journal":"ACS applied bio materials, 8(4), 3061-3075","doi":"10.1021/acsabm.4c01891","pmid":"40131166","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Two thymine-conjugated nucleopeptides formed hydrogels in water at neutral pH via antiparallel β-sheet structures with π-π stacking and H-bonding. Antimicrobial activity against MDR clinical isolates: MRSA (MIC 15.92-16.86 μM), K. pneumoniae (MIC 8.8-50 μM), P. aeruginosa (active), plus standard B. subtilis and E. coli. Biocompatibility was excellent: IC50 values of 0.5-1.1 mM on HEK-293 cells (30-70× higher than MIC values). In vitro wound healing assays confirmed no disruption of cell or mitochondrial membranes. Nanostructural characterization showed nanofibrillar networks by TEM.","whyItMatters":"MRSA and other MDR pathogens cause life-threatening wound infections with limited treatment options. A self-assembling peptide hydrogel that kills superbugs on contact while being safe for human tissue could serve as an antimicrobial wound dressing — applied directly to infected wounds to kill bacteria and support healing simultaneously. The wide therapeutic window (30-70× between MIC and IC50) is particularly promising for clinical safety.","specificNumbers":"","methodology":"Two amphiphilic nucleopeptides were synthesized by conjugating thymine with peptide amphiphiles. Structural characterization used XRD, FETEM, and various analytical techniques. Self-assembly and hydrogel formation were assessed at neutral pH. Antimicrobial activity was tested against standard ATCC strains and MDR clinical isolates by MIC determination. Biocompatibility was evaluated by MTT assay on HEK-293 cells. Wound healing compatibility was assessed using an in vitro scratch assay with HeLa cells and fluorescence microscopy for membrane/mitochondrial integrity.","limitations":"All experiments were in vitro — no animal wound infection models were used. The MIC values against P. aeruginosa were not specified in the abstract. Hydrogel stability, degradation rate, and sustained antimicrobial release were not characterized. The wound healing assay used HeLa cells (cervical cancer line) rather than primary skin cells or keratinocytes. Long-term biocompatibility and potential immune responses to the thymine-peptide conjugates were not assessed. Manufacturing scalability and cost were not discussed."},{"rthcId":"RPEP-10676","title":"Defining the importance of the arginine loop region of protegrin-1 for antimicrobial activity towards colistin-resistant Klebsiella pneumoniae.","authors":"DeBarro, Christina; Assent, Sofia; Makhecha, Hannah; Radde, Noor; Krishnan, Rakesh; Randalf, Justin; de la Fuente-Nunez, Cesar; Fleeman, Renee M","year":2025,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2025.05.28.656599","pmid":"40502092","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10677","title":"Association between GLP-1 receptor agonist use and neurosurgical intervention in patients with idiopathic intracranial hypertension and obesity: a propensity-matched, multi-institutional, cohort study.","authors":"Debiec, Jaylene Cassandra; Toth, Allison; Singh, Romil; Mateti, Nihas; Saim, Muhammad; Shakeel, Hassan A; Luther, Evan","year":2025,"journal":"Journal of neurointerventional surgery","doi":"10.1136/jnis-2025-024139","pmid":"40987589","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10678","title":"Immunoinformatic approach to design an efficient multi-epitope peptide vaccine against melanoma.","authors":"Dehghankhold, Mahvash; Nezafat, Navid; Farahmandnejad, Mitra; Abolmaali, Samira Sadat; Tamaddon, Ali Mohammad","year":2025,"journal":"Biotechnology and applied biochemistry, 72(1), 164-186","doi":"10.1002/bab.2654","pmid":"39245893","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The computationally designed multi-epitope vaccine incorporating NY-ESO-1 and MAGE-C2 antigens demonstrated favorable properties across multiple simulation analyses. The vaccine construct showed satisfactory allergenicity profiles, strong antigenicity, and good physicochemical properties.\n\nMolecular docking and dynamics simulations confirmed stable interactions with TLR2 and TLR4 immune receptors. In silico immune simulation predicted significant increases in helper T cells, cytotoxic T cells, interferon-gamma, and interleukin-2 after repeated vaccine exposure — all key components of an anti-tumor immune response. The inclusion of BCSP31, RpfB adjuvants, and PADRE helper epitope enhanced the overall immunogenicity of the construct.","whyItMatters":"Designing vaccines through computer simulation before doing expensive lab work is becoming a powerful approach in cancer immunotherapy. This study demonstrates the immunoinformatics pipeline for melanoma — predicting which peptide fragments will trigger immune responses, then assembling them into an optimized vaccine design. If validated in the lab, multi-epitope vaccines like this could provide more targeted, less toxic treatment for melanoma patients.","specificNumbers":"","methodology":"Entirely computational (in silico) study. Researchers selected NY-ESO-1 and MAGE-C2 as target antigens based on their immunogenicity and melanoma expression. They used immunoinformatic tools to predict T cell epitopes, then assembled a multi-epitope construct with adjuvants and linkers. The vaccine was evaluated computationally for physicochemical properties, allergenicity, antigenicity, 3D structure quality, molecular docking with TLR2/TLR4 receptors, molecular dynamics stability, and immune response simulation.","limitations":"This is entirely a computational study — no laboratory experiments, animal testing, or human trials were conducted. Computer predictions of immune responses often don't translate directly to real biological systems. The accuracy of the immunoinformatic tools used has limitations, particularly for predicting complex immune interactions. The vaccine has not been synthesized or tested for actual efficacy or safety. Many computationally promising vaccines fail when tested experimentally."},{"rthcId":"RPEP-10679","title":"β-Lactamase cleavable antimicrobial peptide-drug conjugates.","authors":"Deingruber, Tomas; Gaynord, Josephine S; Gan, Bee Ha; Kostadinova, Kristina A; O'Brien, Thomas J; Tan, Yaw Sing; Parker, Jeremy S; Hunt, Thomas A; Carroll, Jason S; Welch, Martin; Spring, David R","year":2025,"journal":"Chemical science, 16(41), 19288-19295","doi":"10.1039/d5sc06369h","pmid":"40979881","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10680","title":"Real-world effectiveness of Semaglutide treatment on weight loss maintenance after weight loss in patients with obesity or overweight and diabetes.","authors":"Del Prete, Michela; Gavazzi, Lidia; Disoteo, Olga Eugenia; Vignati, Federico; Di Sacco, Gianleone; Muratori, Fabrizio","year":2025,"journal":"Eating and weight disorders : EWD, 30(1), 2","doi":"10.1007/s40519-024-01711-2","pmid":"39786599","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"**Injectable semaglutide (n=129):**\n- 6 months: -10.4 kg weight, -3.9 kg/m² BMI, -1.9% HbA1c\n- 12 months: -9.3 kg weight, -3.4 kg/m² BMI, -1.5% HbA1c\n- 24 months: -15.9 kg weight, -5.8 kg/m² BMI, -1.5% HbA1c\n\n**Oral semaglutide (n=46):**\n- 6 months: -6.7 kg weight, -2.6 kg/m² BMI, -1.5% HbA1c\n- 12 months: -10.7 kg weight, -3.9 kg/m² BMI, -0.8% HbA1c\n\nNotably, weight loss was maintained and even continued to increase through 24 months with injectable semaglutide — contradicting concerns about weight plateau or regain during extended treatment. The oral formulation showed comparable effectiveness to injectable at 12 months despite initial slower weight loss.","whyItMatters":"Real-world data fills a critical gap between clinical trial efficacy and actual clinical practice. Patients in trials are carefully selected and monitored, while real-world patients have comorbidities, variable adherence, and diverse lifestyles. This study confirms that semaglutide's weight loss and glycemic benefits persist in everyday practice, and that weight continues to improve through 24 months — addressing the common patient concern of 'will it keep working?'","specificNumbers":"","methodology":"Retrospective real-world study of 175 patients with type 2 diabetes and obesity/overweight treated with injectable semaglutide (n=129) or oral semaglutide (n=46) in clinical practice. Weight, BMI, and HbA1c were measured at baseline, 6, 12, and 24 months (24-month data available for injectable group only).","limitations":"This is a retrospective study without randomization between injectable and oral groups — the groups differed in age, sex distribution, and baseline characteristics. There's no placebo comparison. The 24-month data is only available for injectable semaglutide, preventing long-term comparison with the oral form. Dropout and adherence data are not clearly reported. Specific semaglutide doses are not detailed. The single-center Italian population may not be representative of all patient groups."},{"rthcId":"RPEP-10681","title":"Equine Doping Controls of Thymosin β 4: A Population Study and Strategy for Misuse Detection.","authors":"Delcourt, Vivian; Garcia, Patrice; Chabot, Benjamin; Aber, Nina; Pescher, Mylène; Cacault, Marie; Scholtes, Priscilla; Loup, Benoit; Barnabé, Agnès; Popot, Marie-Agnès; Bailly-Chouriberry, Ludovic","year":2025,"journal":"Drug testing and analysis, 17(7), 1071-1077","doi":"10.1002/dta.3806","pmid":"39314109","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The study established the first population reference range for endogenous TB4 concentration in racehorse blood. TB4 levels were not significantly affected by gender, age, or horse breed. A critical pre-analytical finding was that TB4 concentrations increase significantly and rapidly in plasma stored at 4°C without cell separation, due to cell lysis releasing intracellular TB4.\n\nMost significantly, the researchers demonstrated that administration of a commercially available TB4 product to a horse resulted in detectable non-natural synthesis impurities in equine plasma, providing a reliable marker for doping detection.","whyItMatters":"TB4 is one of the most commonly discussed peptides in performance enhancement circles, marketed online for tissue repair and regeneration. This study is significant because it provides anti-doping laboratories with both baseline reference values and a concrete detection method. The finding that synthetic impurities can be detected from a single dose makes doping controls for this peptide practically feasible for the first time.","specificNumbers":"","methodology":"Population study measuring endogenous TB4 concentrations in blood samples from racing horses across different genders, ages, and breeds. Pre-analytical stability experiments tested the effect of delayed plasma separation on TB4 concentrations. An administration study gave a single dose of a commercial TB4-containing product to a horse and tested plasma for non-natural synthesis impurities as a doping detection strategy.","limitations":"The administration study used a single horse with a single dose, limiting the generalizability of the impurity detection findings. The study focuses on equine physiology and may not directly translate to human TB4 reference ranges. The specific synthesis impurity detected is not named, and different manufacturers may produce products with different impurity profiles. Long-term detection windows after administration are not reported."},{"rthcId":"RPEP-10682","title":"PIONEER REAL Spain: A multicentre, prospective, real-world study of oral semaglutide use in adults with type 2 diabetes.","authors":"Delgado Álvarez, Elías; Morales Portillo, Cristóbal; Abreu Padín, Cristina; Aliaga Verdugo, Alberto; Piera Carbonell, Ana; Cadenas González, Aída; Amor Valero, Jaime; González López, Verónica; Rasmussen, Christina Louise; Scheuer, Stine Hedegaard; Bellido Guerrero, Diego","year":2025,"journal":"Diabetes, obesity & metabolism, 27(9), 4812-4824","doi":"10.1111/dom.16523","pmid":"40555703","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10683","title":"Inhibitory and disinhibitory VIP IN-mediated circuits in neocortex.","authors":"Dellal, Shlomo; Zurita, Hector; Kruglikov, Ilya; Valero, Manuel; Abad-Perez, Pablo; Geron, Erez; Meng, John Hongyu; Prönneke, Alvar; Hanson, Jessica L; Mir, Ema; Ongaro, Marina; Wang, Xiao-Jing; Buzsáki, György; Machold, Robert; Rudy, Bernardo","year":2025,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2025.02.26.640383","pmid":"40060562","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10684","title":"A Novel Peptoid Hybrid of Alpha-Calcitonin Gene-Related Peptide (α-CGRP) Ameliorates Cardiac Remodeling in Pressure Overload-Induced Heart Failure.","authors":"Deloach, Sarah; Kumar, Ambrish; Ruggiero, Emily; Ball, Ryan; Gleason, Kamryn; Kubinak, Jason; DiPette, Donald J; Potts, Jay D","year":2025,"journal":"Cells, 14(20)","doi":"10.3390/cells14201580","pmid":"41148794","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10685","title":"Dual GLP-1 and GIP Agonist Tirzepatide Exerted Neuroprotective Action in a Parkinson's Disease Rat Model.","authors":"Delvadia, Prashant; Dhote, Vipin; Mandloi, Avinash Singh; Soni, Ritu; Shah, Jigna","year":2025,"journal":"ACS chemical neuroscience, 16(5), 818-825","doi":"10.1021/acschemneuro.4c00729","pmid":"39964252","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In a rotenone-induced Parkinson's disease rat model, tirzepatide (50 and 100 nmol/kg, subcutaneous) demonstrated multiple neuroprotective effects:\n\n- Prevented rotenone-induced motor deficits\n- Significantly inhibited proinflammatory cytokines TNF-α and IL-6\n- Upregulated striatal dopamine levels\n- Alleviated oxidative stress\n- Reduced alpha-synuclein aggregation\n- Effects were dose-dependent, with 100 nmol/kg more effective than 50 nmol/kg\n- Neuroprotection was comparable to the GLP-1 agonist exendin-4 (8 μg/kg), supporting the potential benefit of dual GLP-1/GIP receptor activation","whyItMatters":"Parkinson's disease currently has no treatments that slow its progression — all approved drugs only manage symptoms. The finding that tirzepatide protects dopamine-producing neurons and reduces alpha-synuclein aggregation in rats suggests it might slow neurodegeneration. Since tirzepatide is already approved for other conditions, repurposing it for Parkinson's could be faster than developing a new drug from scratch.","specificNumbers":"","methodology":"Rats received rotenone (2 mg/kg) to induce Parkinson's-like pathology. Treatment groups received tirzepatide (50 or 100 nmol/kg, subcutaneous) or exendin-4 (8 μg/kg, subcutaneous). Researchers assessed behavioral/motor function, oxidative stress markers, inflammatory markers (TNF-α, IL-6), striatal dopamine levels, and alpha-synuclein expression.","limitations":"This was an animal study using a chemical model of Parkinson's disease, which doesn't fully replicate the human disease. Rotenone-induced PD is an acute toxicity model, while human Parkinson's develops over decades. The doses used may not correspond to human therapeutic doses. The study did not assess long-term neuroprotection or whether tirzepatide's effects persist after discontinuation. No histological assessment of dopamine neuron survival was described in the abstract."},{"rthcId":"RPEP-10686","title":"Evaluation of the Efficacy and Safety of CollaSel PRO® Type I and Type III Hydrolyzed Collagen Peptides in the Treatment of Osteoarthritis: A Double-Blind, Placebo-Controlled, Randomized Clinical Trial.","authors":"Demir-Dora, Devrim; Tuna, Serpil; Kurtoglu, Emel Dogan; Gursoy, Savas; Balci, Nilufer; Tezman, Selim; Erenmemisoglu, Aydin","year":2025,"journal":"Journal of clinical medicine, 14(11)","doi":"10.3390/jcm14113655","pmid":"40507417","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10687","title":"Protective Effects of BPC 157 on Liver, Kidney, and Lung Distant Organ Damage in Rats with Experimental Lower-Extremity Ischemia-Reperfusion Injury.","authors":"Demirtaş, Hüseyin; Özer, Abdullah; Yıldırım, Alperen Kutay; Dursun, Ali Doğan; Sezen, Şaban Cem; Arslan, Mustafa","year":2025,"journal":"Medicina (Kaunas, Lithuania), 61(2)","doi":"10.3390/medicina61020291","pmid":"40005408","tags":["bpc-157"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"BPC-157 significantly protected the liver, kidneys, and lungs from damage caused by ischemia-reperfusion injury in the lower extremities of rats. In the group that received BPC-157 before the procedure, kidney tissue showed markedly less vacuolization, tubular dilation, and cell shedding. Lung tissue had reduced edema and congestion, and liver tissue showed less sinusoidal dilation, necrosis, and immune cell infiltration.\n\nBiochemical markers backed up the tissue findings: antioxidant activity (measured by TAS) was significantly higher in all three organs of BPC-157-treated rats, while oxidative stress markers (TOS and OSI) were lower. The antioxidant enzyme PON-1 was also elevated in the treatment group.","whyItMatters":"When blood flow is cut off and then restored to a limb — as happens during surgery, trauma, or tourniquet use — the resulting inflammatory cascade can damage organs far from the original injury site. This study suggests BPC-157 may help protect those distant organs by boosting antioxidant defenses and reducing inflammation, though this has only been shown in rats so far.","specificNumbers":"n=24 rats · 4 groups of 6 · 45 min ischemia + 2 h reperfusion · significant increases in TAS and PON-1 in liver, kidney, and lung · significant decreases in TOS and OSI","methodology":"24 male Wistar albino rats were divided into four groups of six: sham, BPC-157 only, ischemia-reperfusion (I/R) only, and I/R plus BPC-157. The I/R groups had blood flow to the lower extremities blocked for 45 minutes, followed by 2 hours of restored blood flow. BPC-157 was administered at the start of the procedure. After reperfusion, liver, kidney, and lung tissues were collected for both histopathological examination and biochemical analysis of oxidative stress markers.","limitations":"This is an animal study with only 6 rats per group, so findings may not translate to humans. The study used a single dose of BPC-157 given preventively before injury, which doesn't reflect how it might be used clinically. Long-term effects and optimal dosing were not explored. The specific dose of BPC-157 used is not detailed in the abstract."},{"rthcId":"RPEP-10688","title":"Effect of the glucagon-like peptide-1 receptor agonists dulaglutide on kidney outcomes in db/db mice.","authors":"Deng, Fengyi; Zhang, Ping; Li, Huaiyun; Fan, Xingyu; Du, Yijun; Zhong, Xing; Wang, Nuojin; He, Meiwen; Wang, Yue; Pan, Tianrong","year":2025,"journal":"Cellular signalling, 127, 111603","doi":"10.1016/j.cellsig.2025.111603","pmid":"39805329","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10689","title":"Level of Expression of MHCI-Presented Neoepitopes Influences Tumor Rejection by Neoantigen-Specific CD8+ T Cells.","authors":"Deng, Li; Walsh, Scott R; Nguyen, Andrew; Inkol, Jordon M; Westerveld, Michael J; Chen, Lan; El-Sayes, Nader; Mossman, Karen L; Workenhe, Samuel T; Wan, Yonghong","year":2025,"journal":"Cancer immunology research, 13(1), 84-97","doi":"10.1158/2326-6066.CIR-23-0639","pmid":"39377761","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Vaccine-induced T cell responses against multiple MC38 tumor neoantigens were immunogenic (generated strong T cell responses) but failed to regress established tumors or prevent tumor engraftment prophylactically. However, these same T cells showed robust killing of cells that were externally loaded with neoantigen peptide. Tumor-cell killing was rescued when target peptide-MHC complexes were saturated on the cell surface. This demonstrates that the level of neoantigen protein expression and MHC-I presentation — not just immunogenicity — determines whether a neoantigen can serve as an effective vaccine target.","whyItMatters":"This study explains a fundamental gap in personalized cancer vaccine development. Current neoantigen prediction algorithms primarily assess whether a peptide mutation will bind MHC and generate an immune response (immunogenicity). But this study shows that's not enough — the target protein must also be expressed at sufficient levels for the neoantigen to be displayed on the tumor surface in quantities that T cells can detect. Adding expression-level analysis to prediction pipelines could dramatically improve vaccine target selection.","specificNumbers":"","methodology":"Mouse study using the MC38 colon cancer model. Multiple neoantigen peptide targets were identified and used to vaccinate mice. T cell responses were measured to confirm immunogenicity. Vaccinated mice were challenged with MC38 tumors (both therapeutic and prophylactic settings). T cell killing was tested against tumor cells and peptide-loaded cells. Peptide-MHC saturation experiments determined the threshold of surface presentation needed for T cell-mediated killing.","limitations":"This is a mouse study using a single tumor model (MC38). The MC38 model has specific immunological characteristics that may not represent all human cancers. The neoantigen targets studied may not be representative of the full diversity of human neoantigens. The peptide-loading rescue experiment demonstrates the principle but uses artificially high peptide concentrations."},{"rthcId":"RPEP-10690","title":"Level of Expression of MHCI-Presented Neoepitopes Influences Tumor Rejection by Neoantigen-Specific CD8+ T Cells.","authors":"Deng, Li; Walsh, Scott R; Nguyen, Andrew; Inkol, Jordon M; Westerveld, Michael J; Chen, Lan; El-Sayes, Nader; Mossman, Karen L; Workenhe, Samuel T; Wan, Yonghong","year":2025,"journal":"Cancer immunology research, 13(1), 84-97","doi":"10.1158/2326-6066.CIR-23-0639","pmid":"39377761","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10691","title":"First assessments of nutrient bioaccessibility with an INFOGEST semi-dynamic gastric digestion in vitro protocol adapted to model proton pump inhibitor use.","authors":"Deng, Ruoxuan; Nau, Françoise; Lucas, Tiphaine; Maillard, Marie-Bernadette; Leduc, Arlette; Ossemond, Jordane; Musse, Maja; Le Feunteun, Steven","year":2025,"journal":"Food research international (Ottawa, Ont.), 203, 115833","doi":"10.1016/j.foodres.2025.115833","pmid":"40022357","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10692","title":"Roles of glucagon-like peptide 1 receptor agonists in immune cell biology and autoimmune/autoinflammatory diseases.","authors":"Deng, Sihui; Chen, Zeyu; Shi, Yuling","year":2025,"journal":"Cell & bioscience, 15(1), 137","doi":"10.1186/s13578-025-01486-8","pmid":"41074143","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 receptor agonists exhibit immunoregulatory effects beyond their well-established metabolic benefits. The review synthesizes evidence showing that GLP-1R signaling affects multiple immune cell types, modulating both innate and adaptive immune responses.\n\nThe therapeutic potential of GLP-1RAs is evaluated across seven autoimmune and autoinflammatory conditions: psoriasis, inflammatory bowel diseases, rheumatoid arthritis, asthma, multiple sclerosis, Sjögren's syndrome, and systemic lupus erythematosus. Evidence comes from in vitro studies, preclinical animal models, and clinical observations in patients taking GLP-1RAs for metabolic indications who showed improvements in co-existing autoimmune conditions.","whyItMatters":"With tens of millions of people now taking GLP-1 receptor agonists for diabetes and obesity, understanding their immune effects has become urgent. If these drugs genuinely modulate autoimmune disease activity, they could represent a massive expansion of their therapeutic value — potentially treating conditions that affect hundreds of millions of people globally. This review provides the scientific foundation for that emerging field.","specificNumbers":"","methodology":"This is a narrative review synthesizing evidence from in vitro studies examining GLP-1R signaling in immune cells, preclinical animal models of autoimmune diseases treated with GLP-1RAs, and clinical observations and case reports of patients with autoimmune conditions who received GLP-1RAs for diabetes or obesity.","limitations":"Most evidence for autoimmune applications comes from preclinical models and clinical observations rather than dedicated randomized controlled trials. The immunomodulatory effects may be partially indirect — mediated through weight loss and metabolic improvements rather than direct immune cell effects. Different GLP-1RAs may have different immunological profiles. The review does not assess potential risks of immunosuppression from GLP-1R signaling modulation."},{"rthcId":"RPEP-10693","title":"Flash pulmonary edema caused by paroxysmal supraventricular tachycardia in a patient with preserved ejection fraction.","authors":"Deng, Tingzhi; Li, Ding; Liang, Lihui; Ou, Baiqing","year":2025,"journal":"BMC cardiovascular disorders, 25(1), 747","doi":"10.1186/s12872-025-05238-x","pmid":"41120913","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10694","title":"Clinical characteristics and outcomes of patients with type 2 diabetes mellitus and chronic kidney disease from two new-user medication cohorts: a retrospective cohort study using regional electronic health records database in China.","authors":"Deng, Xiaoqing; Chen, Yanyan; Xu, Zhe; Wei, Huan; Liao, Yuqin; Liu, Fangfang; Farjat, Alfredo E; Oberprieler, Nikolaus G; Chen, Liming","year":2025,"journal":"BMJ open, 15(12), e106126","doi":"10.1136/bmjopen-2025-106126","pmid":"41448677","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10695","title":"Fine-Tuning Side Chain Substitutions: Impacts on the Lipophilicity-Solubility-Permeability Interplay in Macrocyclic Peptides.","authors":"Deng, Yangping; Bian, Hengwei; Li, Hongbo; Cui, Yingjun; Li, Sizheng; Li, Jing; Chen, Li; Zhang, Xuemei; Shen, Zhuo; Li, Fengyue; Chen, Yue; Fu, Haohao","year":2025,"journal":"Marine drugs, 24(1)","doi":"10.3390/md24010013","pmid":"41590710","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10696","title":"T7 peptide-modified erythrocyte membrane-camouflaged amphiphilic self-delivery biomimetic nanodrug for targeting therapy oral squamous cell carcinoma.","authors":"Deng, Yun; Yan, Wangxiang; Shu, Dalong; Zhu, Li; Chen, Songling; Chen, Yu","year":2025,"journal":"Materials today. Bio, 35, 102345","doi":"10.1016/j.mtbio.2025.102345","pmid":"41069687","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10697","title":"Promising results but caution needed in GLP-1RA large scale epidemiology.","authors":"Deo, Salil V; Sattar, Naveed A","year":2025,"journal":"Trends in endocrinology and metabolism: TEM, 36(6), 504-506","doi":"10.1016/j.tem.2025.03.015","pmid":"40280862","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10698","title":"Liraglutide vs Semaglutide vs Dulaglutide in Veterans With Type 2 Diabetes.","authors":"Derington, Catherine G; Sarwal, Amara; Wei, Guo; Hartsell, Sydney E; Throolin, Michael; Singh, Ravinder; Nevers, McKenna R; Zhang, Chong; Katkam, Niharika; Takyi, Augustine; Chakravartula, Akhil R; Babu, Poorvika; Deshmukh, Vikrant G; Boucher, Robert E; Drakos, Stavros G; Greene, Tom; Shen, Jincheng; Beddhu, Srinivasan","year":2025,"journal":"JAMA network open, 8(10), e2537297","doi":"10.1001/jamanetworkopen.2025.37297","pmid":"41082229","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In this large comparative effectiveness study of 21,790 veterans with type 2 diabetes, liraglutide, semaglutide, and dulaglutide showed no significant differences in kidney failure or cardiovascular outcomes. Kidney failure hazard ratios were similar across all comparisons (e.g., liraglutide vs semaglutide HR 0.93, 95% CI 0.60–1.44), and the composite cardiovascular-kidney-metabolic outcome and major adverse cardiovascular events were also comparable.\n\nThe most notable finding involved all-cause mortality. Liraglutide was associated with a 31% lower hazard of death compared to dulaglutide in intent-to-treat analysis (HR 0.69, 95% CI 0.58–0.83) and a 50% lower hazard in per-protocol analysis (HR 0.50, 95% CI 0.31–0.82). Liraglutide also showed a trend toward lower mortality versus semaglutide (HR 0.83, 95% CI 0.69–0.99), though this lost statistical significance in per-protocol models. For gastrointestinal side effects, dulaglutide was associated with lower risk of gallstones (HR 0.72) and acute cholecystitis (HR 0.62) compared to semaglutide.","whyItMatters":"GLP-1 receptor agonists have become a cornerstone of type 2 diabetes treatment, but most evidence comes from placebo-controlled trials rather than head-to-head comparisons. Clinicians and patients need to know whether one GLP-1RA offers meaningful advantages over another. This large real-world study provides reassurance that the three most commonly used GLP-1RAs are broadly comparable for heart and kidney protection, while flagging potential mortality differences that warrant confirmation in randomized trials.","specificNumbers":"","methodology":"This was a comparative effectiveness study using a target trial-emulation design, linking national data from the VA health system, Medicare, and the US Renal Data System. Researchers identified veterans with type 2 diabetes who were new users of liraglutide, semaglutide, or dulaglutide between 2018 and 2021, all of whom were already on metformin and did not have end-stage kidney disease. They used weighted Cox regression models to compare outcomes including kidney failure, cardiovascular events, death, and gastrointestinal adverse events through March 2023.","limitations":"As an observational study, even with careful statistical adjustments, residual confounding cannot be ruled out — differences in why doctors prescribed one drug over another could influence outcomes. The study population was predominantly male veterans (91%), which limits generalizability to women and non-veteran populations. The mortality advantage for liraglutide lost significance in some per-protocol analyses, suggesting the finding may not be robust. Additionally, the study period (2018–2021) included the early COVID-19 pandemic, which may have affected outcomes in ways that are difficult to account for."},{"rthcId":"RPEP-10699","title":"Efficacy of tirzepatide for weight loss and it's comparative effectiveness to weight loss surgery in inflammatory bowel disease.","authors":"Desai, Aakash; Khataniar, Himsikhar; Tabaku, Fjona; Hashash, Jana G; Farraye, Francis A; Kochhar, Gursimran S","year":2025,"journal":"Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology","doi":"10.1007/s12664-025-01835-y","pmid":"40682732","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10700","title":"NT-pro Brain Natriuretic Peptide in Infants with Single Ventricle Heart Disease in the CHAMP® Multi-site Registry.","authors":"Desai, Atharva; Noel-Macdonnell, Janelle R; Erickson, Lori A; Ricketts, Amy; Elliott, Melissa; Moehlmann, Matthew; Romans, Ryan A; Jayaram, Natalie; Hancock, Hayley S","year":2025,"journal":"Pediatric cardiology","doi":"10.1007/s00246-025-03999-y","pmid":"40841470","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10701","title":"Intractable Vomiting in the Setting of Glucagon-Like Peptide-1 (GLP-1) Receptor Agonist and Cannabis Usage.","authors":"DesRochers, Peter; Kaiser, Linus; Lee, Seoyoon; Perchetti, Garrett A; Lazarescu, Roxana","year":2025,"journal":"Cureus, 17(11), e97851","doi":"10.7759/cureus.97851","pmid":"41458667","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A 55-year-old woman with chronic kidney disease, type 2 diabetes with neuropathy, peripheral vascular disease, and prior pancreatitis developed severe gastrointestinal symptoms consistent with the temporal relationship of GLP-1 receptor agonist dose titration. The case was complicated by sepsis physiology, gastrointestinal bleeding, hemodynamic instability, and metabolic derangement, requiring multidisciplinary management including endocrinology, gastroenterology, and cardiology.","whyItMatters":"As GLP-1 receptor agonists like tirzepatide become widely prescribed, understanding their risks in complex patients is critical. While GI side effects are well-known and usually mild, this case shows they can escalate to life-threatening complications in patients with multiple comorbidities. It underscores the need for cautious dose titration and close monitoring in high-risk populations.","specificNumbers":"","methodology":"Single patient case report describing the clinical presentation, hospital course, and management of a complex adverse drug reaction following tirzepatide up-titration in a multimorbid patient. Concurrent cannabis use was noted as a potential complicating factor.","limitations":"As a single case report, this cannot establish incidence rates or definitively attribute all complications to tirzepatide. The patient had multiple pre-existing conditions (CKD, prior pancreatitis, neuropathy) and concurrent cannabis use, making it difficult to isolate the drug's contribution. The findings represent one extreme scenario and should not be generalized to typical GLP-1 RA users."},{"rthcId":"RPEP-10702","title":"Coated glucose microbeads stimulate enteric hormone release and improve glucose tolerance in Phase 1 and 2 clinical trials.","authors":"Deusch, Kai; Deboek, Arthur; Sina, Christian; Capo-Velez, Coral; Alicea, Vivianette; Duller, Stephan; Grafe, Susanne; Lidington, Darcy; Hanchard, Julia; Bolz, Steffen-Sebastian","year":2025,"journal":"Diabetes, obesity & metabolism, 27(12), 7344-7354","doi":"10.1111/dom.70135","pmid":"40959944","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10703","title":"Impact of glucagon-like peptide-1 receptor agonists on axonal function in diabetic peripheral neuropathy.","authors":"Dhanapalaratnam, Roshan; Issar, Tushar; Poynten, Ann M; Milner, Kerry-Lee; Kwai, Natalie C G; Krishnan, Arun V","year":2025,"journal":"Journal of neurophysiology, 133(1), 14-21","doi":"10.1152/jn.00228.2024","pmid":"39584713","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Twenty-four participants with diabetic peripheral neuropathy treated with GLP-1 receptor agonists showed significant improvement in clinical neuropathy scores (TNS improved from 3.7 to 2.3, p=0.005) and nerve conduction (sural nerve amplitude improved from 11.9 to 14.2 μV, p=0.013) after 3 months. Axonal excitability testing revealed improvements consistent with enhanced Na+/K+-ATPase pump function and Na+ permeability, supported by mathematical modeling. Three GLP-1RAs were used: semaglutide, dulaglutide, and exenatide.","whyItMatters":"Diabetic peripheral neuropathy has been considered 'relentlessly progressive and irreversible' — there are no approved disease-modifying treatments. The finding that GLP-1 receptor agonists can improve nerve function in just 3 months is potentially paradigm-shifting. Since millions of people are already taking these drugs for diabetes and obesity, this represents a major potential bonus benefit for a devastating complication that currently has no effective treatment.","specificNumbers":"n=24 · 3-month follow-up · TNS improved: 3.7→2.3 (p=0.005) · Sural amplitude: 11.9→14.2 μV (p=0.013) · Improved Na+/K+-ATPase pump function · 3 GLP-1RAs: semaglutide, dulaglutide, exenatide","methodology":"Prospective observational study. Fourteen participants newly prescribed semaglutide or dulaglutide for type 2 diabetes underwent clinical assessment, nerve conduction studies, and axonal excitability testing at baseline and 3 months. These data were combined with 10 participants previously studied on exenatide therapy (total n=24). Mathematical modeling of axonal excitability data was performed to identify mechanisms of improvement.","limitations":"This is a small, open-label observational study (n=24) without a control group or randomization. Improvements could partly reflect better glycemic control rather than direct neuroprotective effects. The 3-month follow-up is short — longer studies are needed to determine if benefits are sustained. Combining data from three different GLP-1RAs and two separate cohorts introduces heterogeneity."},{"rthcId":"RPEP-10704","title":"Sacubitril/valsartan as add-on to standard therapy in patients with heart failure: A randomized controlled trial.","authors":"Dhawan, Reevanshi; Mittal, Rakesh; Kumar, Ashwani; Laller, Kuldip S; Gill, Paramjeet S; Rag, Adarsh; Mittal, Niti","year":2025,"journal":"World journal of experimental medicine, 15(4), 111542","doi":"10.5493/wjem.v15.i4.111542","pmid":"41497676","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10705","title":"Angiotensin Receptor Neprilysin Inhibitor in Heart Failure With Preserved Ejection Fraction and Secondary Mitral Regurgitation: Design and Rationale of the PRAISE-MR Trial.","authors":"Dhont, Sebastiaan; Ferreira, Sara Moura; Galloo, Xavier; Martens, Pieter; Meekers, Evelyne; Tartaglia, Katrien; Deferm, Sébastien; Herbots, Lieven; Mullens, Wilfried; Verbrugge, Frederik H; Verwerft, Jan; Bertrand, Philippe B","year":2025,"journal":"Journal of cardiac failure","doi":"10.1016/j.cardfail.2025.05.019","pmid":"40562090","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10706","title":"Glucagon-like peptide-1 receptor agonists and suicide risk in individuals with diabetes and Cannabis use disorder.","authors":"Dhruva, Yesh; Messias, Erick; Lin, Ping-I","year":2025,"journal":"Preventive medicine reports, 58, 103244","doi":"10.1016/j.pmedr.2025.103244","pmid":"41050856","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 6,424,228 T2DM adults, GLP-1RA use was associated with significantly lower suicide attempt risk (aHR: 0.63; 95% CI: 0.47-0.85). Cannabis use disorder (CUD) dramatically elevated risk (aHR: 5.50; 95% CI: 4.39-6.89). Among CUD patients using GLP-1RAs, the elevated risk persisted (aHR: 5.75; 95% CI: 3.42-9.69) with no protective GLP-1RA effect (aHR: 1.00; 95% CI: 0.37-2.69 for GLP-1RA effect within CUD group).","whyItMatters":"The European Medicines Agency investigated whether GLP-1 drugs increase suicide risk in 2023 after safety signals were reported. This study — the largest to date examining this question — not only finds no increased risk but actually shows a protective association. This is enormously reassuring for the tens of millions of people taking these drugs. The cannabis use finding adds important clinical nuance: mental health screening and substance use assessment remain critical in this population.","specificNumbers":"","methodology":"Retrospective cohort study using the TriNetX Research Network (>20 countries, 2003-2023). Adults 30-85 with T2DM were categorized by GLP-1RA exposure and cannabis use disorder. Patients with prior suicidal ideation were excluded. Cox proportional hazards models estimated hazard ratios adjusted for age, sex, depression, BMI, and HbA1c. Kaplan-Meier survival analysis visualized cumulative risk over one year.","limitations":"Retrospective observational design cannot establish causation. The TriNetX database may have coding inconsistencies across 20+ countries. GLP-1RA users may differ from non-users in unmeasured ways (healthier patient bias). Cannabis use disorder may be underdiagnosed in claims data. The one-year follow-up may miss longer-term effects. Suicidal ideation exclusion removes patients at already-elevated risk."},{"rthcId":"RPEP-10707","title":"Elucidating associations between technetium pyrophosphate scintigraphy, echocardiography and cardiac biomarkers in transthyretin cardiac amyloidosis.","authors":"Di Giovanni, Bennett; Gustafson, Dakota; Arivalagan, Priya; Adamson, Mitchell B; Vishram-Nielsen, Julie; Delgado, Diego","year":2025,"journal":"Open heart, 12(2)","doi":"10.1136/openhrt-2024-002686","pmid":"40841121","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Positive 99mTc-PYP grading was significantly associated with increased left ventricular mass (β=111.21, p=0.009) and greater interventricular septal thickness (β=0.48, p=0.003) in hereditary ATTR patients. Nuclear scan positivity also correlated with log-transformed BNP (β=1.99, p=0.002) in hereditary patients and log-transformed troponin (β=1.68, p=0.007) in wild-type ATTR patients.\n\nThe quantitative heart-to-contralateral lung ratio from nuclear imaging did not correlate with BNP or troponin but was significantly associated with LV mass (β=134.52, p=0.001) and septal thickness (β=0.46, p=0.002) in hereditary patients. These genotype-dependent differences support a stratified diagnostic approach.","whyItMatters":"Transthyretin amyloidosis is increasingly recognized as an underdiagnosed cause of heart failure, especially in elderly men. Understanding how different diagnostic tools relate to each other helps clinicians interpret results more accurately, monitor disease progression, and potentially guide treatment decisions — particularly with emerging therapies like tafamidis that can stabilize transthyretin.","specificNumbers":"","methodology":"Single-center retrospective cohort study of 183 patients aged 18+ diagnosed with transthyretin cardiac amyloidosis at Toronto General Hospital between October 2012 and December 2022. Linear regression and multivariate proportional hazard models examined associations between 99mTc-PYP scintigraphy findings, echocardiographic parameters, and cardiac biomarkers (troponin I and BNP).","limitations":"This is a single-center retrospective study, which may limit generalizability. The sample size of 183, while reasonable for this rare condition, limits the power of subgroup analyses by genotype. The study period (2012-2022) spans a time of evolving diagnostic criteria and awareness, which could introduce bias. Longitudinal associations and prognostic value of the identified correlations were not the primary focus."},{"rthcId":"RPEP-10708","title":"Sleeve gastrectomy versus dual GLP-1/GIP receptor agonist to improve access to kidney transplantation in patients with end-stage renal disease and obesity: A decision analysis.","authors":"Di Napoli, Marissa; Rouhi, Armaun D; Baimas-George, Maria; Dumon, Kristoffel; Castle, Rose; Kennealey, Peter; Nydam, Trevor; Choudhury, Rashikh","year":2025,"journal":"American journal of surgery, 250, 116475","doi":"10.1016/j.amjsurg.2025.116475","pmid":"40540976","tags":["GLP-1-agonists","obesity"],"studyType":"modeling-study","evidenceStrength":"low-moderate","keyFinding":"Using a Markov decision model, researchers compared three weight loss strategies for morbidly obese patients with end-stage kidney disease who need to reach BMI ≤35 to qualify for kidney transplant. At 5 years, sleeve gastrectomy got the most patients to transplant (14.74%), followed by dual GLP-1/GIP receptor agonists like tirzepatide (9.06%), and single GLP-1 agonists (4.83%).\n\nSleeve gastrectomy produced faster weight loss, with 27.49% of patients reaching the BMI target by 6 months. Surgery also showed a survival advantage, especially in patients starting at higher BMIs.\n\nHowever, dual GLP-1/GIP agonists still got a substantial number of patients to transplant and represent a viable non-surgical alternative, particularly for patients who cannot undergo or prefer to avoid surgery.","whyItMatters":"Obese patients with kidney failure face a cruel catch-22: they need a transplant to survive, but many transplant programs require BMI below 35 first. This study quantifies how different weight loss strategies affect the odds of actually reaching that threshold and getting a kidney. It shows surgery is fastest, but the newer dual-agonist drugs offer a meaningful pharmaceutical alternative — especially important for patients too sick for elective surgery.","specificNumbers":"14.74% transplant rate with surgery at 5 years · 9.06% with dual GLP-1/GIP agonist · 4.83% with single GLP-1 agonist · 27.49% reached BMI ≤35 by 6 months with surgery","methodology":"Markov state transition model simulating outcomes for morbidly obese patients with end-stage renal disease under three weight loss interventions. Patients transitioned between health states based on weight loss trajectories, transplant eligibility (BMI ≤35 kg/m²), and survival. Model parameters were derived from published literature on each intervention.","limitations":"This is a mathematical model, not a clinical trial — results depend entirely on the assumptions and input parameters used. Real-world outcomes may differ due to patient adherence, complications, drug availability, and individual variation in weight loss response. The model does not account for weight regain after initial loss or complications specific to dialysis patients undergoing surgery."},{"rthcId":"RPEP-10709","title":"Obesity update: cardiovascular risk and therapeutic innovations (focus on semaglutide and tirzepatide).","authors":"Di Odoardo, Luca Antonio Felice; Zucchetti, Ottavio; Sciatti, Edoardo; D'Isa, Salvatore; D'Elia, Emilia; Senni, Michele","year":2025,"journal":"European heart journal supplements : journal of the European Society of Cardiology, 27(Suppl 3), iii137-iii142","doi":"10.1093/eurheartjsupp/suaf032","pmid":"40248309","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10710","title":"Glucagon-Like Peptide-1 receptor agonists, dual GIP/GLP-1 receptor agonist tirzepatide and suicidal ideation and behavior: A systematic review of clinical studies and pharmacovigilance reports.","authors":"Di Stefano, Ramona; Rindi, Lorenzo V; Baldini, Valentina; Rossi, Rodolfo; Pacitti, Francesca; Jannini, Emmanuele A; Rossi, Alessandro","year":2025,"journal":"Diabetes & metabolic syndrome, 19(4), 103238","doi":"10.1016/j.dsx.2025.103238","pmid":"40388845","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10711","title":"Weight Management Strategies to Reduce Metabolic Morbidity in Women With Polycystic Ovary Syndrome.","authors":"Diakosavvas, Michail; Oyebode, Oyinlola; Bhide, Priya","year":2025,"journal":"Current obesity reports, 14(1), 22","doi":"10.1007/s13679-025-00614-2","pmid":"40045077","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10712","title":"Prevention of cardiovascular events in heart failure with mildly reduced or preserved ejection fraction: a comprehensive network meta-analysis of eight randomized controlled trials using reconstructed individual patient's data.","authors":"Diallo, Alhassane; Carlos-Bolumbu, Miguel; Duc, Philippe; Galtier, Florence","year":2025,"journal":"EClinicalMedicine, 88, 103506","doi":"10.1016/j.eclinm.2025.103506","pmid":"41181824","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10713","title":"Cathelicidin LL37-loaded extracellular vesicles from Edwardsiella piscicida promote antibacterial and wound-healing activity.","authors":"Dias, Mawalle Kankanamge Hasitha Madhawa; Jayathilaka, E H T Thulshan; De Zoysa, Mahanama","year":2025,"journal":"Scientific reports, 15(1), 45724","doi":"10.1038/s41598-025-28377-9","pmid":"41331000","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10714","title":"Lateral Septum as a Key Integrative Regulator of Feeding: Role of the GLP-1/GLP-1R System.","authors":"Dib, Tatiana; Covarrubias, María José; Escobar, Angélica; Renard, Georgina M; Bravo, Javier A; Sotomayor-Zárate, Ramón","year":2025,"journal":"Journal of neurochemistry, 169(11), e70301","doi":"10.1111/jnc.70301","pmid":"41277798","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The lateral septum serves as a neural relay center integrating homeostatic (nutritional need-driven) and hedonic (pleasure-driven) feeding circuits. GLP-1 receptors are present in the LS, and their activation within this region modulates food intake. The extensive neural connections between the LS and other brain regions involved in feeding behavior position it as a critical node where GLP-1 signaling may influence eating through multiple pathways simultaneously.","whyItMatters":"GLP-1 receptor agonists like semaglutide are among the most effective obesity treatments available, but exactly how they reduce appetite in the brain is still being mapped out. Identifying the lateral septum as an important site of GLP-1 action advances our understanding of these drugs' mechanisms and could help develop more targeted or effective future therapies.","specificNumbers":"","methodology":"This is a narrative review synthesizing recent findings on the lateral septum's role in feeding regulation and the GLP-1/GLP-1R system within this brain region. The authors draw on neuroanatomical, neurochemical, and behavioral studies to build their argument.","limitations":"As a narrative review, this paper synthesizes existing evidence but does not present new experimental data. Much of the evidence for GLP-1R function in the lateral septum comes from animal models, and direct human evidence is limited. The review advocates for future research rather than providing definitive conclusions about the LS as a therapeutic target."},{"rthcId":"RPEP-10715","title":"Key Signals Produced by Gut Microbiota Associated with Metabolic Syndrome, Cancer, Cardiovascular Diseases, and Brain Functions.","authors":"Dicks, Leon M T","year":2025,"journal":"International journal of molecular sciences, 26(21)","doi":"10.3390/ijms262110539","pmid":"41226575","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review highlights several key peptide-related signaling pathways influenced by gut microbiota:\n\n- GLP-1: Activation of brainstem NTS by GLP-1 influences mood, cognition, and gastrointestinal motility\n- Prolactin-releasing peptide (PrRP): Binds to PrRPR to suppress food intake and regulate stress, cardiovascular reactions, and circadian rhythms\n- GPR119: Suppresses appetite with potential applications in type 2 diabetes and obesity treatment\n- SCFAs interact with GPCRs, TLRs, and PPARs to influence inflammatory reactions, gut motility, hormone secretion, and neurochemical signaling\n- Olfactory receptor OR51E1 influences blood pressure and vascular reactivity\n- Butyrate binding to NF-κB and PPARγ regulates inflammation and prevents oxidized LDL uptake, reducing cardiovascular disease risk","whyItMatters":"The gut-brain axis and gut microbiome are revolutionizing our understanding of chronic diseases. This review connects the dots between gut bacteria and the peptide hormone signals they influence — providing the biological rationale for why microbiome-based interventions could treat conditions ranging from obesity to depression to heart disease.","specificNumbers":"","methodology":"Narrative review synthesizing animal and preclinical studies from PubMed, NIH, ScienceDirect, MDPI, Frontiers, Cell Press, and CAS Content Collection, focusing on gut microbiota signaling in metabolic syndrome, cancer, cardiovascular disease, and brain functions.","limitations":"The review acknowledges that in-depth studies on how gut microbiota control cognitive behavior, mood, and neuropsychiatric disorders are lacking. Most evidence comes from animal and preclinical studies. The causal relationships between specific bacterial species and peptide signaling are not well established. Translation of microbiome findings to clinical interventions remains challenging."},{"rthcId":"RPEP-10716","title":"Asymptomatic Subcutaneous Semaglutide Overdose: A Case Report and Literature Review.","authors":"Diec, Courtney B; Cook, Elizabeth A; Nguyen, Nguyet T","year":2025,"journal":"Journal of pharmacy practice, 8971900251335111","doi":"10.1177/08971900251335111","pmid":"40232990","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10717","title":"Branched penetratin and penetramax display enhanced intestinal insulin delivery potency compared to their linear counterparts.","authors":"Diedrichsen, Ragna Guldsmed; Mishra, Narendra Kumar; Fredholt, Freja; Heade, Joanne; Sørensen, Kasper Kildegaard; Jensen, Knud Jørgen; Nielsen, Hanne Mørck","year":2025,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 380, 1031-1042","doi":"10.1016/j.jconrel.2025.02.044","pmid":"39983923","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Branching cell-penetrating peptides (penetratin and penetramax) into dimer and trimer structures significantly increased their ability to enhance transepithelial permeation of insulin and other cargo molecules across Caco-2 cell monolayers. The enhancement correlated with the degree of branching — trimers outperformed dimers, which outperformed linear forms. The mechanism involved immediate and reversible effects on cell monolayer integrity and cytoskeletal alterations, consistent with paracellular transport. In vivo pharmacokinetic studies in rats confirmed that dimeric penetramax enhanced intestinal insulin delivery compared to linear penetramax.","whyItMatters":"Oral insulin has been a goal of diabetes research for decades, but the intestinal barrier has been the primary obstacle. Cell-penetrating peptides are among the most promising carriers, and this study shows that a simple structural modification — branching into dimers and trimers — dramatically increases their delivery potency. The reversibility of the effects on intestinal cells is also encouraging for safety.","specificNumbers":"Dimer and trimer variants tested · Penetratin and penetramax peptides · Branching increased potency proportionally · Reversible effects on cell monolayers · In vivo confirmation with dimeric penetramax","methodology":"Combined in vitro and in vivo study. Linear, dimer, and trimer versions of penetratin and penetramax were synthesized and tested using Caco-2 cell culture models for transepithelial permeation of insulin, dextran, mannitol, and metoprolol. Cell monolayer integrity and cytoskeletal changes were assessed. In vivo pharmacokinetic studies in rats evaluated dimeric penetramax as an insulin carrier, with histological assessment of intestinal tissue safety.","limitations":"Caco-2 cell models, while standard, do not fully replicate the complexity of the human intestine (mucus layer, immune cells, variable conditions). Only dimeric penetramax was tested in vivo, not the trimer variants. Long-term safety of repeated dosing with branched peptide carriers was not assessed. Specific blood glucose reduction data or bioavailability percentages are not provided in the abstract."},{"rthcId":"RPEP-10718","title":"Hypothalamic GHRH.","authors":"Dieguez, Carlos; López, Miguel; Casanueva, Felipe","year":2025,"journal":"Reviews in endocrine & metabolic disorders, 26(3), 297-303","doi":"10.1007/s11154-025-09951-y","pmid":"39913072","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10719","title":"Utility of Pharmacological Agents for Diabetes Mellitus in the Prevention of Alzheimer's Disease: Comparison of Metformin, Glucagon-Like Peptide-1 (GLP-1) Agonists, Insulin, and Sulfonylureas.","authors":"DiGiovanni, Alexandra; Shehaj, Andrea; Millar, David; Tse, Claire; Rizk, Elias","year":2025,"journal":"Cureus, 17(7), e87350","doi":"10.7759/cureus.87350","pmid":"40761983","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10720","title":"Liraglutide as a novel therapeutic for overweight in canines: A clinical study.","authors":"Dik, Burak; Hatipoglu, Durmuş; Kahraman, Oguzhan; Parlak, Tugba Melike; Inanc, Zekeriya Safa; Celik, Metin; Damar, Samed","year":2025,"journal":"Veterinary journal (London, England : 1997), 313, 106376","doi":"10.1016/j.tvjl.2025.106376","pmid":"40436366","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10721","title":"Glucagon-like peptide 1 receptor agonists and renal outcomes in kidney transplant recipients with diabetes mellitus.","authors":"Diker Cohen, Talia; Rudman, Yaron; Turjeman, Adi; Akirov, Amit; Steinmetz, Tali; Calvarysky, Bronya; Dotan, Idit","year":2025,"journal":"Diabetes & metabolism, 51(3), 101624","doi":"10.1016/j.diabet.2025.101624","pmid":"39961479","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10722","title":"Effects of Dulaglutide on Ectopic Fat Deposition in Chronic Kidney Disease (CKD): A Pilot and Feasibility Study (GLIMP).","authors":"Dilaver, Ragibe Gulsah; Afsar, Rengin Elsurer; Crescenzi, Rachelle; Gamboa, Jorge; Ikizler, Talat Alp","year":2025,"journal":"medRxiv : the preprint server for health sciences","doi":"10.1101/2025.03.19.25324266","pmid":"40166561","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10723","title":"Rapid cleavage of 6-[18F]fluoronicotinic acid prosthetic group governs BT12 glioblastoma xenograft uptake: implications for radiolabeling design of biomolecules.","authors":"Dillemuth, Pyry; Ayo, Abiodun; Zhuang, Xiaoqing; Lövdahl, Petter; Liljenbäck, Heidi; Kärnä, Salli; Auchynnikava, Tatsiana; Kunnas, Jonne; Ponkamo, Jesse; Miner, Maxwell W G; Rajander, Johan; Rosenholm, Jessica M; Roivainen, Anne; Airaksinen, Anu J; Laakkonen, Pirjo; Li, Xiang-Guo","year":2025,"journal":"EJNMMI radiopharmacy and chemistry, 10(1), 40","doi":"10.1186/s41181-025-00368-1","pmid":"40629197","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10724","title":"Preventing Allogeneic Stem Cell Transplant-Related Cardiovascular Dysfunction: ALLO-Active Trial.","authors":"Dillon, Hayley T; Saner, Nicholas J; Ilsley, Tegan; Kliman, David S; Foulkes, Stephen J; Brakenridge, Christian J; Spencer, Andrew; Avery, Sharon; Claus, Piet; Dunstan, David W; Daly, Robin M; Fraser, Steve F; Owen, Neville; Lynch, Brigid M; Kingwell, Bronwyn A; La Gerche, Andre; Howden, Erin J","year":2025,"journal":"Circulation, 151(4), 292-308","doi":"10.1161/CIRCULATIONAHA.124.070709","pmid":"39492713","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10725","title":"The role of GLP-1 in the pathophysiology and treatment of sepsis: a narrative review.","authors":"Dimic, Nemanja; Djuric, Marko; Vejapi, Maja; Nenadic, Irina; Bobos, Marina; Bojic, Suzana; Savic, Predrag; Milanovic, Miljan; Stevanovic, Predrag","year":2025,"journal":"Frontiers in medicine, 12, 1612034","doi":"10.3389/fmed.2025.1612034","pmid":"41357527","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10726","title":"The management of hypothalamic obesity in craniopharyngioma.","authors":"Dimitri, Paul","year":2025,"journal":"Best practice & research. Clinical endocrinology & metabolism, 39(5), 102018","doi":"10.1016/j.beem.2025.102018","pmid":"40514321","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10727","title":"Physicochemical, medicinal chemistry, and ADMET characteristics of bee antimicrobial peptides as natural bio-preservatives to extend food shelf life: a roadmap for food safety regulation.","authors":"Dinata, Roy; Arati, Chettri; Saeed, Ahmed-Laskar; Manikandan, Bose; Abinash, Giri; Pori, Buragohain; Bidanchi, Rema Momin; Roy, Vikas Kumar; Gurusubramanian, Guruswami","year":2025,"journal":"Journal of biomolecular structure & dynamics, 43(18), 10609-10637","doi":"10.1080/07391102.2024.2429181","pmid":"39573920","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Using three computational platforms (ADMETlab, OECD QSAR toolbox, and VEGA HUB), 82 peptide sequences from seven bee antimicrobial peptides (abaecin, apamin, apisimin, apidaecin, defensin, hymenoptaecin, and melittin) were profiled against 81 descriptors.\n\nKey findings across all seven BAMPs:\n- Met drug-likeness rules from Lipinski, Pfizer, and GSK\n- Predicted favorable cell permeability, high water solubility, and oral bioavailability\n- No blood-brain barrier penetration predicted\n- Non-substrates of p-glycoprotein\n- No cytochrome P450 enzyme inhibition (no drug-drug interaction risk)\n- Free of respiratory toxicity, hepatotoxicity, carcinogenicity, and mutagenicity\n- No toxicophore or PAINS (pan-assay interference) alerts\n- Predicted antibacterial, antifungal, and antiviral activity\n- Non-toxic to gonadal receptors, stress receptors, PPAR-γ, mitochondrial membrane receptors, and p53","whyItMatters":"Antimicrobial resistance is a global health crisis, and finding alternatives to conventional antibiotics is urgent. Bee antimicrobial peptides are promising because they use mechanisms that bacteria have difficulty developing resistance against. This comprehensive computational profiling demonstrates that these natural peptides already possess many properties needed for drug development, potentially shortcutting the early discovery phase and accelerating their path toward pharmaceutical and food safety applications.","specificNumbers":"","methodology":"The researchers used three virtual computational environments — ADMETlab, OECD QSAR toolbox, and VEGA HUB — to profile 82 peptide sequences from seven known bee antimicrobial peptides. Each sequence was evaluated against 81 descriptors covering physicochemical properties, medicinal chemistry parameters, absorption/distribution/metabolism/excretion/toxicity (ADMET) profiles, and toxicophore screening. No wet-lab experiments were performed.","limitations":"This is entirely a computational study — all findings are predictions from in silico models, not experimental measurements. Computational ADMET predictions, while useful for screening, frequently diverge from actual laboratory and clinical results. No wet-lab validation of the predicted properties was performed. The study also does not address the practical challenges of manufacturing these peptides at scale or their stability in food matrices."},{"rthcId":"RPEP-10728","title":"KLF9 aggravates the cardiomyocyte hypertrophy in hypertrophic obstructive cardiomyopathy through the lncRNA UCA1/p27 axis.","authors":"Ding, Dayou; Zhao, Guangrong","year":2025,"journal":"International journal of experimental pathology, 106(2), e12526","doi":"10.1111/iep.12526","pmid":"39909852","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10729","title":"Exendin-4 induced retching-like behavior mediated by postsynaptic effect via AMPA receptors in the area postrema of mice.","authors":"Ding, Hanting; Wang, Mengtian; Zhang, Jian; Wan, Chenchen; Huang, Zhaohuan; Liu, Ling; Liu, Ji","year":2025,"journal":"American journal of physiology. Endocrinology and metabolism, 329(2), E254-E265","doi":"10.1152/ajpendo.00174.2025","pmid":"40622911","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10730","title":"Microbiome and metabolomic changes in rabbits induced by Folium sennae.","authors":"Ding, Houkang; Li, Ming; Ma, Ning; Rajput, Shahid Ali; Almutairi, Mikhlid H; Almutairi, Bader O; Han, Zhaoqing; Ma, Aituan; Shiau, Dengshan","year":2025,"journal":"PloS one, 20(3), e0320496","doi":"10.1371/journal.pone.0320496","pmid":"40163454","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10731","title":"Bone mineral density and turnover response to GLP-1 receptor agonists in older adults with overweight/obesity and prediabetes/type 2 diabetes: a 20-week pilot trial post hoc analysis.","authors":"Dinkla, Lauren; Beavers, Kristen M; Robbins, Ronna; Akpalu, Dela; Wherry, Sarah J; Miller, Gary; Beavers, Daniel P; Espinoza, Sara; Trejo, Jonathan; Stepanenko, Allison; Cortes, Tiffany M","year":2025,"journal":"Frontiers in aging, 6, 1691007","doi":"10.3389/fragi.2025.1691007","pmid":"41393101","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10732","title":"Efficacy and safety of once-weekly semaglutide monotherapy in a young subject with Prader-Willi syndrome, obesity, and type 2 diabetes: a case report.","authors":"Dinoi, Elisa; Daniele, Giuseppe; Michelucci, Angela; Baldinotti, Fulvia; Campi, Fabrizio; Marchetti, Piero; Del Prato, Stefano; Dardano, Angela","year":2025,"journal":"Frontiers in endocrinology, 16, 1533209","doi":"10.3389/fendo.2025.1533209","pmid":"39996062","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10733","title":"Molecular Design of Unimolecular Tetra-Receptor Agonists.","authors":"Dinsmore, Tristan C; Cortigiano, Jacob E; Xiang, Siyuan; Spenciner, Marina V; Dobbins, Alexandra R; Zhao, Richard L; Waldman, Brett M; Beinborn, Martin; Kumar, Krishna","year":2025,"journal":"Journal of the American Chemical Society, 147(24), 20819-20832","doi":"10.1021/jacs.5c04095","pmid":"40461942","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10734","title":"New Perspectives in Modulating the Entero-Insular Axis in Pediatric Obesity.","authors":"Dira, Loredana-Maria; Marin, Loredana-Maria; Popa, Simona-Georgiana; Singer, Cristina-Elena; Cosoveanu, Carmen-Simona; Donoiu, Ionut; Golli, Andreea-Loredana","year":2025,"journal":"International journal of molecular sciences, 26(13)","doi":"10.3390/ijms26136143","pmid":"40649920","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10735","title":"Cell penetrating peptide-functionalized small interfering RNA nanoparticles knock down HER expression in breast cancer cells.","authors":"Dissanayake, Ranga; Mishra, Vineet Kumar; Ahmed, Marya","year":2025,"journal":"The Journal of pharmacology and experimental therapeutics, 392(12), 103697","doi":"10.1016/j.jpet.2025.103697","pmid":"41478672","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10736","title":"Controlled self-assembly of macrocyclic peptide into multifunctional photoluminescent nanoparticles.","authors":"Dissanayake, Ranga; Nazeer, Nauman; Zarei, Zeyaealdin; Bhayo, Adnan Murad; Ahmed, Marya","year":2025,"journal":"Journal of pharmaceutical sciences, 114(2), 990-1001","doi":"10.1016/j.xphs.2024.11.006","pmid":"39551234","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10737","title":"Semaglutide 2.4 mg in French people living with Class 3 obesity and comorbidities: Baseline characteristics and real-world safety data.","authors":"Disse, Emmanuel; Aron-Wisnewsky, Judith; Jacobi, David; Clément, Karine; Laville, Martine; Gauthier, Cyril; Pattou, François; Molleville, Julie; Akerib, Melissa; Jubin, Lysiane; Gatta-Cherifi, Blandine; Gaborit, Bénédicte; Montastier, Emilie; Stenard, Fabien; Carette, Claire; Achamrah, Najate; Avignon, Antoine; Czernichow, Sébastien","year":2025,"journal":"Diabetes & metabolism, 51(3), 101625","doi":"10.1016/j.diabet.2025.101625","pmid":"39971183","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10738","title":"Compounded glucagon-like peptide-1 receptor agonists for weight loss: the direct-to-consumer market in Colorado.","authors":"DiStefano, Michael J; Dardouri, Mouna; Moore, Gina D; Saseen, Joseph J; Nair, Kavita V","year":2025,"journal":"Journal of pharmaceutical policy and practice, 18(1), 2441220","doi":"10.1080/20523211.2024.2441220","pmid":"39776466","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10739","title":"Glucagon-Like Peptide-1 (GLP-1) Agents and Cardiovascular Risk in Non-diabetic Patients: A Descriptive Analysis of National Health and Nutrition Examination Survey (NHANES), 2011-2018.","authors":"Disu, Fatimot; Okoro, Nkiruka L; Mochu, Adaora W; Martey, Andrew R; Shittu, Salihu; Green, Joshua T; Azubike, Williams C","year":2025,"journal":"Cureus, 17(10), e94373","doi":"10.7759/cureus.94373","pmid":"41230299","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10740","title":"Effects of Semaglutide on Muscle Structure and Function in the SLIM LIVER Study.","authors":"Ditzenberger, Grace L; Lake, Jordan E; Kitch, Douglas W; Kantor, Amy; Muthupillai, Raja; Moser, Carlee; Belaunzaran-Zamudio, Pablo F; Brown, Todd T; Corey, Kathleen; Landay, Alan L; Avihingsanon, Anchalee; Sattler, Fred R; Erlandson, Kristine M","year":2025,"journal":"Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 80(2), 389-396","doi":"10.1093/cid/ciae384","pmid":"39046173","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10741","title":"Enhanced localized pressure-mediated non-viral gene delivery.","authors":"Dixon, James E; Wellington, Vanessa; Elnima, Alaa; Savers, Amelie; Ferreras, Lia A Blokpoel; Jalal, Aveen R; Eltaher, Hoda M","year":2025,"journal":"Drug delivery and translational research, 15(10), 3679-3694","doi":"10.1007/s13346-025-01827-7","pmid":"40072728","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10742","title":"Vitamin D3 loaded polycaprolactone nanoparticles enhance the expression of the antimicrobial peptide cathelicidin in macrophages.","authors":"Dlozi, Prince N; Ahmed, Rami; Khoza, Star; Dube, Admire","year":2025,"journal":"Artificial cells, nanomedicine, and biotechnology, 53(1), 207-219","doi":"10.1080/21691401.2025.2499515","pmid":"40327417","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10743","title":"Glucagon-Like Peptide-1 Use and Healthcare Resource Utilization for Depression and Anxiety Among Adults with Type 2 Diabetes: 2019 to 2023.","authors":"Do, Duy; Lee, Tiffany; Inneh, Angela; Patel, Urvashi","year":2025,"journal":"The journal of behavioral health services & research","doi":"10.1007/s11414-025-09950-6","pmid":"40439835","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In a retrospective cohort of 774,968 adults with T2DM, GLP-1 receptor agonist initiation was associated with significantly reduced mental health-related healthcare utilization compared to DPP-4 inhibitor initiation:\n\n- Office visits for depression: IRR 0.87 (95% CI 0.82–0.92) — 13% reduction\n- Office visits for anxiety: IRR 0.85 (95% CI 0.81–0.90) — 15% reduction\n- Outpatient hospital visits for depression: IRR 0.96 (95% CI 0.95–0.98) — 4% reduction\n\nNo significant changes were observed for emergency department or inpatient visits. Reductions were more pronounced with semaglutide, liraglutide, and dulaglutide specifically.","whyItMatters":"Depression and anxiety affect up to 40% of people with type 2 diabetes, worsening their health outcomes and driving up healthcare costs. If GLP-1 drugs can reduce the mental health burden alongside their metabolic benefits, this represents a significant additional value proposition. This large real-world study provides early evidence that the mental health benefits observed in smaller studies may translate into measurable reductions in healthcare utilization at a population level.","specificNumbers":"","methodology":"This was a retrospective cohort study using the Komodo Healthcare Map, a national database of pharmacy and medical claims. Adults who initiated GLP-1 receptor agonists or DPP-4 inhibitors between January 2019 and March 2022 were included (n=774,968). Patients were followed for 12 months after medication initiation. A difference-in-differences analysis compared mental health-related healthcare resource utilization (HCRU) before and after initiation, adjusting for sociodemographic and clinical variables. Outcomes included emergency department, inpatient, outpatient hospital, and office visits for depression and anxiety.","limitations":"This is an observational study using claims data, which cannot establish causation. Reduced mental health visits could reflect improved mental health OR reduced access/engagement with care. Claims data lacks clinical detail — we don't know if patients actually felt less depressed or anxious. There may be selection bias: patients prescribed GLP-1 drugs may differ systematically from those prescribed DPP-4 inhibitors. The 12-month follow-up is relatively short. Emergency and inpatient visits showed no change, which could indicate the benefit is limited to milder presentations."},{"rthcId":"RPEP-10744","title":"Exploiting the angiotensin-converting enzyme pathway to augment endogenous opioid signaling.","authors":"Dobariya, Prakashkumar; Williams, Jessica; Hanak, Filip; Rothwell, Patrick E; More, Swati S","year":2025,"journal":"Communications biology, 8(1), 1465","doi":"10.1038/s42003-025-08790-6","pmid":"41087507","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10745","title":"Exploiting the Angiotensin-Converting Enzyme Pathway to Augment Endogenous Opioid Signaling.","authors":"Dobariya, Prakashkumar; Williams, Jessica; Hanak, Filip; Rothwell, Patrick E; More, Swati S","year":2025,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2025.02.19.639161","pmid":"40060674","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10746","title":"Patient With Tirzepatide-treated Type 2 Diabetes With Difficult Visualization During Esophagogastroduodenoscopy.","authors":"Dobashi, Hiroki; Shioya, Daiki; Kikkawa, Koji; Ohshima, Kihachi; Okada, Junichi; Okada, Shuichi","year":2025,"journal":"JCEM case reports, 3(4), luaf044","doi":"10.1210/jcemcr/luaf044","pmid":"40123805","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10747","title":"Effect of erenumab versus other migraine preventive medications on cardiovascular and cerebrovascular outcomes: A United States claims database-based observational cohort study.","authors":"Dodick, David W; Tepper, Stewart J; Ailani, Jessica; Khodavirdi, Ani C; Pannacciulli, Nico; Fu, Alan; Kent, Shia T; Gill, Karminder; Urman, Robert; Oh, Sam S","year":2025,"journal":"Headache, 65(6), 919-932","doi":"10.1111/head.14912","pmid":"40033803","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 108,019 new users of migraine preventive medications, the 12-month unadjusted risk of new-onset hypertension was essentially identical across treatment groups: erenumab 9.34%, other anti-CGRP mAbs 9.42%, standard oral preventives 9.09%, and onabotulinumtoxinA 9.10%.\n\nAt 36 months, adjusted relative risks for acute myocardial infarction and stroke showed no significant differences: erenumab vs. other mAbs — MI: RR 1.02 (95% CI 0.45–1.59), stroke: RR 0.90 (0.56–1.25); erenumab vs. onabotulinumtoxinA — MI: RR 0.87 (0.19–1.55), stroke: RR 0.97 (0.42–1.52). No elevated cardiovascular risk was identified for erenumab.","whyItMatters":"CGRP is a potent vasodilator, raising theoretical concerns that blocking it with drugs like erenumab could cause blood vessel constriction and cardiovascular events. This large real-world study provides reassuring evidence that these concerns have not materialized in clinical practice, supporting continued confidence in anti-CGRP migraine therapies for the millions of patients who use them.","specificNumbers":"","methodology":"Retrospective observational cohort study using the MarketScan Commercial and Medicare Supplemental medical claims database. Researchers compared new-onset rates of hypertension, acute myocardial infarction, and stroke among new users of erenumab, other anti-CGRP mAbs, standard oral preventive medications, and onabotulinumtoxinA. Inverse probability weighting addressed measured confounders, and negative control outcome analyses evaluated unmeasured confounding.","limitations":"This is an observational study using insurance claims data, which may have coding inaccuracies and cannot capture all clinical variables. While negative control outcomes suggested minimal unmeasured confounding for key comparisons, residual confounding cannot be entirely excluded. The comparison with standard oral preventives showed potential confounding concerns. The study population may not fully represent uninsured or underinsured patients."},{"rthcId":"RPEP-10748","title":"Are glucagon-like peptide-1 (GLP-1) receptor agonists useful in treating Parkinson's disease (PD)? Does the clinical trial with lixisenatide add anything?","authors":"Doggrell, Sheila A","year":2025,"journal":"Expert opinion on investigational drugs, 34(1-2), 11-15","doi":"10.1080/13543784.2025.2459409","pmid":"39864104","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10749","title":"Uptitration of Sacubitril/Valsartan in Acute Heart Failure: Insight from the PREMIER Study.","authors":"Doi, Shunichi; Tanaka, Atsushi; Kida, Keisuke; Imai, Takumi; Ueda, Yusuke; Nakano, Yukiko; Kizaki, Yoshihisa; Fukuda, Daiju; Matsue, Yuya; Akashi, Yoshihiro J; Node, Koichi","year":2025,"journal":"Journal of cardiac failure","doi":"10.1016/j.cardfail.2025.05.001","pmid":"40389107","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10750","title":"Hydrogen Sulfide Deficiency and Therapeutic Targeting in Cardiometabolic HFpEF: Evidence for Synergistic Benefit With GLP-1/Glucagon Agonism.","authors":"Doiron, Jake E; Elbatreek, Mahmoud H; Xia, Huijing; Yu, Xiaoman; Gehred, Natalie D; Gromova, Tatiana; Chen, Jingshu; Driver, Ian H; Muraoka, Naoto; Jensen, Martin; Shambhu, Smitha; Tang, W H Wilson; LaPenna, Kyle B; Sharp, Thomas E; Goodchild, Traci T; Xian, Ming; Xu, Shi; Quiriarte, Heather; Allerton, Timothy D; Zagouras, Alexia; Wilcox, Jennifer; Shah, Sanjiv J; Pfeilschifter, Josef; Beck, Karl-Friedrich; Vondriska, Thomas M; Li, Zhen; Lefer, David J","year":2025,"journal":"JACC. Basic to translational science, 10(10), 101297","doi":"10.1016/j.jacbts.2025.04.011","pmid":"40772898","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10751","title":"Hydrogen Sulfide Deficiency and Therapeutic Targeting in Cardiometabolic HFpEF: Evidence for Synergistic Benefit with GLP-1/Glucagon Agonism.","authors":"Doiron, Jake E; Elbatreek, Mahmoud H; Xia, Huijing; Yu, Xiaoman; Gehred, Natalie D; Gromova, Tatiana; Chen, Jingshu; Driver, Ian H; Muraoka, Naoto; Jensen, Martin; Shambhu, Smitha; Tang, W H Wilson; LaPenna, Kyle B; Sharp, Thomas E; Goodchild, Traci T; Xian, Ming; Xu, Shi; Quiriarte, Heather; Allerton, Timothy D; Zagouras, Alexia; Wilcox, Jennifer; Shah, Sanjiv J; Pfeilschifter, Josef; Beck, Karl-Friedrich; Vondriska, Thomas M; Li, Zhen; Lefer, David J","year":2025,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2024.09.16.613349","pmid":"39345440","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Hydrogen sulfide levels were reduced by 81% in human HFpEF patients and were similarly depleted in two rodent models of cardiometabolic HFpEF. This depletion was linked to reduced CSE enzyme expression and activity alongside increased SQR expression.\n\nGenetic knockout of CSE in endothelial cells worsened HFpEF features including elevated E/e' ratio and left ventricular end-diastolic pressure, impaired aortic vasorelaxation, and increased mortality. Pharmacological H₂S supplementation restored bioavailability, improved diastolic function, and reduced cardiac fibrosis. Combining the H₂S donor DATS with the GLP-1/glucagon receptor agonist survodutide synergistically reduced obesity, improved diastolic function and exercise capacity, and decreased oxidative stress and cardiac fibrosis in ZSF1 obese rats.","whyItMatters":"HFpEF accounts for roughly half of all heart failure cases and has very limited treatment options. Identifying hydrogen sulfide deficiency as a contributing mechanism opens an entirely new therapeutic avenue. The synergistic benefit with GLP-1/glucagon agonism is particularly exciting because it suggests combination therapies could address both the metabolic and cardiac aspects of this complex disease.","specificNumbers":"","methodology":"The study used a translational approach spanning human patients and two preclinical models. H₂S bioavailability was measured in HFpEF patients and in two rodent HFpEF models: a 'two-hit' L-NAME plus high-fat diet mouse and the ZSF1 obese rat. Researchers used endothelial cell-specific CSE knockout mice to study loss of H₂S production, and tested pharmacological H₂S supplementation (JK-1 and DATS) alone and in combination with survodutide in the rat model.","limitations":"This is a preprint (bioRxiv) that has not yet undergone peer review. The human data shows correlation between H₂S deficiency and HFpEF but cannot establish causation. The combination therapy was only tested in one animal model (ZSF1 rats). Specific dosing protocols and long-term safety of H₂S supplementation in humans remain unknown. The study does not provide human clinical trial data for the combination therapy."},{"rthcId":"RPEP-10752","title":"On the Effect of Melittin on Surface Properties of Erythrocyte and Mitochondrial Membranes.","authors":"Doltchinkova, Virjinia; Vitkova, Victoria; Kitanova, Meglena; Shkodrova, Milena; Lozanova, Siya; Ivanov, Avgust; Roumenin, Chavdar","year":2025,"journal":"Membranes, 16(1)","doi":"10.3390/membranes16010011","pmid":"41590564","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10753","title":"Obesity, diabetes, and inflammation: Pathophysiology and clinical implications.","authors":"Donath, Marc Y; Drucker, Daniel J","year":2025,"journal":"Immunity, 58(10), 2373-2382","doi":"10.1016/j.immuni.2025.09.011","pmid":"41045922","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10754","title":"Impact of GLP-1 receptor agonist-induced weight loss on 22 cancers in the next ten years using a Markov state-transition model - A UK weight and wellness cancer landscape analysis.","authors":"Dong, Jiawen; Starkey, Thomas; Cheng, Vinton W T; Clark, James; Pinato, David J; Robinson, Timothy; Tilby, Michael; Turnbull, Christopher D; Yw Lee, Lennard","year":2025,"journal":"Cancer epidemiology, 97, 102837","doi":"10.1016/j.canep.2025.102837","pmid":"40413897","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10755","title":"Long-term administration of liraglutide for weight management in pediatric patients under 18 years: evidence from 7 randomized controlled trials.","authors":"Dong, Jiayue; Liu, Meilin; Liu, Zhanli","year":2025,"journal":"Pediatric research","doi":"10.1038/s41390-025-04537-5","pmid":"41184626","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10756","title":"Multifunctional hydrogel scaffolds loaded with peptides in promoting wound healing: A review.","authors":"Dong, Sihan; Han, Yuanyuan; Wang, Yulai; Ding, Qiteng; Ding, Chuanbo; Chen, Shengyue; Song, Yupeng; Zhao, Ting","year":2025,"journal":"International journal of biological macromolecules, 330(Pt 3), 148128","doi":"10.1016/j.ijbiomac.2025.148128","pmid":"41067349","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10757","title":"Mazdutide, a dual agonist targeting GLP-1R and GCGR, mitigates diabetes-associated cognitive dysfunction: mechanistic insights from multi-omics analysis.","authors":"Dong, Wanqing; Bai, Jie; Yuan, Qibin; Zhang, Yingyu; Zhang, Yongjiang; Zhang, Ziyue; Yang, Maoxing; Li, Hanxiao; Zhao, Ziyue; Jiang, Hongwei","year":2025,"journal":"EBioMedicine, 117, 105791","doi":"10.1016/j.ebiom.2025.105791","pmid":"40479843","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10758","title":"Plasma neuropeptide Y levels and adverse clinical outcomes after acute ischaemic stroke.","authors":"Dong, Wenjing; Lu, Yaling; Long, Jiayi; Peng, Yanbo; Ju, Zhong; Xu, Tan; Zhang, Yonghong; Zhai, Guojie; Zhong, Chongke","year":2025,"journal":"European journal of neurology, 32(1), e16548","doi":"10.1111/ene.16548","pmid":"39575855","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 3,250 acute ischemic stroke patients followed for 12 months, 702 (21.6%) experienced major disability or death. Patients in the highest quartile of plasma NPY had significantly worse outcomes:\n\n- Primary composite (death + major disability): OR 1.56 (95% CI: 1.19-2.04) vs lowest quartile\n- Per standard deviation increase in log-NPY: OR 1.18 (1.07-1.30) for primary outcome\n- Per SD increase for major disability alone: OR 1.28 (1.15-1.42)\n\nAdding NPY to conventional risk factors improved prediction: category-free net reclassification index 8.82% (P=0.040) and integrated discrimination improvement 0.38% (P=0.011).","whyItMatters":"Stroke is a leading cause of death and disability worldwide, and predicting which patients will have poor outcomes remains challenging. NPY is already known to participate in cardiovascular pathophysiology, and this large study demonstrates its value as a prognostic biomarker specifically in acute stroke. If validated, a simple blood test measuring NPY levels could help clinicians triage acute stroke patients for intensity of care, rehabilitation planning, and clinical trial enrollment.","specificNumbers":"","methodology":"Prospective cohort study nested within the China Antihypertensive Trial in Acute Ischaemic Stroke. Plasma NPY levels were measured in 3,250 patients (2,066 men, 1,184 women) during the acute phase of ischemic stroke. The primary outcome was a composite of death and major disability (modified Rankin Scale ≥3) at 12 months. Secondary outcomes included major disability alone, death, and cardiovascular events. Multivariable logistic regression with adjustment for conventional risk factors was used. Predictive improvement was assessed using reclassification indices.","limitations":"This is an observational study and cannot establish whether elevated NPY is a cause of poor outcomes or simply a marker of more severe stroke/stress response. The cohort is from a single Chinese clinical trial population, which may limit generalizability to other ethnicities. NPY was measured only at the acute phase — serial measurements might provide more prognostic information. The improvement in risk prediction, while statistically significant, was modest (NRI 8.82%, IDI 0.38%). NPY assays are not widely available in clinical laboratories."},{"rthcId":"RPEP-10759","title":"Multicopy Expression of the Marine Antimicrobial Peptide Spgillcin177-189 in Pichia pastoris for High-Yield Production and Potent Activity Against Foodborne Pathogens.","authors":"Dong, Xianxian; Liao, Huiliang; Zhang, Chang; Chen, Fangyi; Peng, Hui; Hong, Xiao; Hao, Hua; Xiong, Ming; Ma, Jiahao; Wang, Ke-Jian","year":2025,"journal":"Probiotics and antimicrobial proteins","doi":"10.1007/s12602-025-10874-y","pmid":"41392233","tags":[],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Researchers achieved high-yield production of the marine antimicrobial peptide Spgillcin177-189 using a multicopy yeast expression system in Pichia pastoris. The multicopy strategy yielded 126.1 mg/L — 2.75 times more than single-copy strains. The recombinant peptide showed potent activity against multiple foodborne pathogens (MIC range 5.25–84 μg/mL), effective bactericidal and anti-biofilm activity against S. aureus and V. parahaemolyticus, good heat stability, and no significant cytotoxicity or hemolysis.\n\nThe peptide works by targeting bacterial cell membranes via hydrogen bonding with surface components, disrupting membrane integrity and causing cell death.","whyItMatters":"Antibiotic resistance in foodborne bacteria and consumer demand for chemical-free food preservation are creating urgent need for natural antimicrobial alternatives. This study solves a key manufacturing bottleneck — producing enough antimicrobial peptide affordably — which is essential for any real-world food safety application.","specificNumbers":"126.1 mg/L yield · 2.75× improvement over single-copy · MIC 5.25–84 μg/mL · active against S. aureus and V. parahaemolyticus · no cytotoxicity or hemolysis","methodology":"Established a Pichia pastoris yeast expression system for recombinant Spgillcin177-189 production. Used Golden Gate assembly technology to construct multicopy plasmids for enhanced expression. Tested antibacterial activity (MIC), bactericidal activity, anti-biofilm activity, thermostability, cytotoxicity, and hemolytic activity. Investigated the mechanism of bacterial membrane disruption.","limitations":"This is an in vitro production and characterization study. The peptide has not been tested in actual food preservation applications or in vivo. Scale-up from laboratory to industrial production remains to be demonstrated. Activity against a limited panel of foodborne pathogens was tested."},{"rthcId":"RPEP-10760","title":"Severe lumbosacral polyradiculopathy secondary to micronutrient deficiencies in a patient on semaglutide therapy following bariatric surgery.","authors":"Donigan, Emma C; Ingersent, Elizabeth; Wanberg, Erik J; Jegen, Dominika A; Passmore, Rachael","year":2025,"journal":"Endocrinology, diabetes & metabolism case reports, 2025(3)","doi":"10.1530/EDM-25-0072","pmid":"40956288","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A 39-year-old male on semaglutide (1.7 mg/week) following transoral outlet reduction surgery presented with severe bilateral lower extremity weakness, loss of reflexes, and sensory impairment. Laboratory testing revealed thiamine and vitamin E deficiencies. MRI showed cauda equina nerve root enhancement without structural abnormalities. He was diagnosed with lumbosacral polyradiculopathy due to micronutrient deficiencies.\n\nSymptoms developed over 3 months and worsened after semaglutide dose increase. Treatment included semaglutide discontinuation, thiamine and vitamin E supplementation, and inpatient rehabilitation. Motor and sensory symptoms improved over the following month.","whyItMatters":"Millions of people are now using GLP-1 receptor agonists like semaglutide, and many have a history of or are considering bariatric surgery. This case highlights a potentially dangerous blind spot: there are established nutritional monitoring guidelines for bariatric surgery patients but almost none for GLP-1RA users, and no guidelines at all for patients using both. As combination weight-loss approaches become more common, nutrient monitoring becomes critical.","specificNumbers":"","methodology":"Single clinical case report. The patient underwent physical examination, laboratory serum testing for micronutrients, and lumbar MRI. Diagnosis was made based on the combination of neurological findings, documented nutrient deficiencies, and absence of structural abnormalities on imaging.","limitations":"This is a single case report, representing the lowest level of clinical evidence. The relative contribution of bariatric surgery versus semaglutide to the nutrient deficiencies cannot be determined. The patient's dietary intake and compliance with post-surgical nutrition recommendations were not detailed. It's unclear whether semaglutide alone (without prior surgery) would pose similar risks. Long-term neurological outcomes were not reported."},{"rthcId":"RPEP-10761","title":"Machine learning to optimize use of natriuretic peptides in the diagnosis of acute heart failure.","authors":"Doudesis, Dimitrios; Lee, Kuan Ken; Anwar, Mohamed; Singer, Adam J; Hollander, Judd E; Chenevier-Gobeaux, Camille; Claessens, Yann-Erick; Wussler, Desiree; Weil, Dominic; Kozhuharov, Nikola; Strebel, Ivo; Sabti, Zaid; deFilippi, Christopher; Seliger, Stephen; Mesquita, Evandro Tinoco; Wiemer, Jan C; Möckel, Martin; Coste, Joel; Jourdain, Patrick; Kimiaki, Komukai; Yoshimura, Michihiro; Ibrahim, Irwani; Ooi, Shirley Beng Suat; Kuan, Win Sen; Gegenhuber, Alfons; Mueller, Thomas; Hanon, Olivier; Vidal, Jean-Sébastien; Cameron, Peter; Lam, Louisa; Freedman, Ben; Chung, Tommy; Collins, Sean P; Lindsell, Christopher J; Newby, David E; Japp, Alan G; Shah, Anoop S V; Villacorta, Humberto; Richards, A Mark; McMurray, John J V; Mueller, Christian; Januzzi, James L; Mills, Nicholas L","year":2025,"journal":"European heart journal. Acute cardiovascular care, 14(8), 474-488","doi":"10.1093/ehjacc/zuaf051","pmid":"40219913","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10762","title":"Therapeutic approaches in the management of chronic kidney disease: the past, the present, and the future.","authors":"Doumani, Georgia; Theofilis, Panagiotis; Vordoni, Aikaterini; Smirloglou, Despina; Kalaitzidis, Rigas G","year":2025,"journal":"Minerva medica, 116(6), 468-482","doi":"10.23736/S0026-4806.25.09747-2","pmid":"41051293","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10763","title":"A GLP-1 analogue optimized for cAMP-biased signaling improves weight loss in obese mice.","authors":"Douros, Jonathan D; Novikoff, Aaron; DuBois, Barent; Rohlfs, Rebecca; Mokrosinski, Jacek; Hogendorf, Wouter F J; Augustin, Robert; Merkestein, Myrte; Egaa Martini, Lene Brandt; Linderoth, Lars; Gerrard, Elliot; Kodra, Janos Tibor; Norlin, Jenny; Roed, Nikolaj Kulahin; Oldenburger, Anouk; Mowery, Stephanie A; Waldhoer, Maria; Perez-Tilve, Diego; Finan, Brian; Reedtz-Runge, Steffen; Müller, Timo D; Knerr, Patrick J","year":2025,"journal":"Molecular metabolism, 100, 102124","doi":"10.1016/j.molmet.2025.102124","pmid":"40157531","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10764","title":"The Premise of the Paradox: Examining the Evidence That Motivated GIPR Agonist and Antagonist Drug Development Programs.","authors":"Douros, Jonathan D; Mowery, Stephanie A; Knerr, Patrick J","year":2025,"journal":"Journal of clinical medicine, 14(11)","doi":"10.3390/jcm14113812","pmid":"40507574","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review synthesizes evidence supporting the paradox:\n\n- GIP receptor agonism (tirzepatide): Activating both GIP and GLP-1 receptors produces greater weight loss and metabolic improvement than GLP-1 alone — demonstrated in clinical trials leading to tirzepatide's approval\n- GIP receptor antagonism (maridebart cafraglutide/MariTide): Blocking GIP while activating GLP-1 also enhances weight loss — demonstrated in early clinical data\n- The paradox is supported by: human genetic evidence (GIPR loss-of-function variants associated with lower BMI), rodent genetic knockout models, and preclinical pharmacology in rodents and non-human primates\n- The review highlights where early preclinical findings successfully predicted clinical efficacy and where the translation was less straightforward","whyItMatters":"Understanding the GIP paradox is critical for the next generation of obesity drugs. If both agonism and antagonism work, it suggests the GIP system is more complex than a simple on/off switch. Resolving this paradox could reveal new mechanisms for weight loss and lead to even more effective peptide drugs — potentially with different side effect profiles that allow more patients to benefit.","specificNumbers":"","methodology":"Narrative review examining human physiology of GIP, human genetic evidence (loss-of-function variants), rodent genetic models (GIPR knockout), preclinical pharmacology studies in rodents and non-human primates, and clinical development data for tirzepatide and MariTide.","limitations":"This is a review without original data. The paradox itself remains unresolved — the review examines the evidence motivating both programs but does not provide a unified mechanistic explanation. Some preclinical findings in rodents may not translate directly to humans. The clinical data for GIPR antagonism (MariTide) are still early-stage compared to the extensive tirzepatide trial program."},{"rthcId":"RPEP-10765","title":"Potential role of glucagon like peptide 1 in taste receptors.","authors":"Doval-Caballero, Jose Luis Eduardo; Ferreira-Hermosillo, Aldo; Eugenio-Ponce, Genesis Dinora; García-Sáenz, Manuel Ramon; Ibarra-Salce, Raúl; Tenorio-Rojo, Andrea Patricia; Luna-Avila, Eduardo Salif; Gete-Palacios, Paulo César; Pérez-Hernández, Fernando; Rojas-Milán, Eduardo; López-Cruz, Luis Angel; Méndez-Hernández, César Alejandro","year":2025,"journal":"Frontiers in endocrinology, 16, 1683419","doi":"10.3389/fendo.2025.1683419","pmid":"41659336","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Gut peptide hormones directly influence taste perception through multiple mechanisms: they regulate taste receptor expression and function in taste buds and the gastrointestinal tract. GLP-1, leptin, ghrelin, and CCK each modulate specific aspects of taste sensitivity at both peripheral (tongue) and central (brain reward circuitry) levels. Metabolic conditions like obesity and diabetes — characterized by hormonal resistance (leptin, insulin) and neurotransmitter dysregulation — contribute to altered taste preferences and compulsive eating behaviors. The review establishes a gut-brain-taste axis integrating peripheral gustatory signals with central homeostatic and hedonic mechanisms.","whyItMatters":"Understanding why GLP-1 drugs change taste perception helps explain one of the most commonly reported but poorly understood effects of these medications. If GLP-1 directly modifies taste bud function, this could be both a therapeutic mechanism (reducing desire for unhealthy foods) and a side effect concern (reducing food enjoyment). The gut-brain-taste axis concept also opens new therapeutic targets — designing drugs that specifically modify taste preferences could complement appetite-suppressing medications.","specificNumbers":"","methodology":"Narrative review synthesizing evidence on how peptide hormones and neuromodulators influence taste receptor biology, gustatory signaling, and feeding behavior. Covers molecular, cellular, and systems-level evidence from animal and human studies.","limitations":"This is a narrative review without systematic methodology. Much of the evidence for direct taste receptor modulation by peptide hormones comes from animal studies and may not translate quantitatively to humans. The mechanisms linking metabolic conditions to taste changes are still being elucidated and may be more complex than presented. Individual variation in taste perception changes with GLP-1 drugs is not addressed."},{"rthcId":"RPEP-10766","title":"Molecular Insights into Tumor Immunogenicity.","authors":"Doytchinova, Irini; Sotirov, Stanislav; Dimitrov, Ivan","year":2025,"journal":"Current issues in molecular biology, 47(8)","doi":"10.3390/cimb47080641","pmid":"40864796","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Analysis of 38 T-cell epitopes and 144 non-epitopes revealed that immunogenic peptides have strong amino acid preferences at central positions p4-p8, while non-epitopes do not.\n\nMolecular dynamics simulations (100 ns) of representative epitope and non-epitope complexes with TCR-peptide-HLA showed:\n- The immunogenic epitope formed a more stable complex with greater flexibility, supporting an induced-fit recognition mechanism\n- It established a broader and longer-lasting network of hydrogen bonds and π interactions across positions p4-p8\n- The non-epitope engaged the TCR at only two positions, explaining its inability to trigger a full immune response\n\nThese findings identify the peptide's central region as the primary driver of TCR engagement and immunogenicity.","whyItMatters":"Cancer immunotherapy depends on identifying which tumor-derived peptides can actually trigger an immune attack. Currently, many predicted neoantigens fail to activate T-cells in practice. Understanding the molecular rules that distinguish immunogenic from non-immunogenic peptides could dramatically improve the success rate of personalized cancer vaccines and help design more effective peptide-based immunotherapies.","specificNumbers":"","methodology":"The researchers compiled two datasets of nine-amino-acid (nonamer) peptides: 38 known T-cell epitopes and 144 non-epitopes that bind HLA but don't activate T-cells. Sequence logo analysis compared amino acid preferences at each position. A representative epitope-non-epitope pair was selected for structural modeling using TCR-peptide-HLA complex structures, followed by 100 nanosecond molecular dynamics simulations to assess binding stability, flexibility, and interaction networks.","limitations":"The study used computational methods (molecular dynamics simulations) rather than experimental validation of the structural findings. The analysis was limited to nonamer peptides binding to specific HLA types, so the findings may not generalize to all peptide lengths and HLA alleles. The datasets were relatively small (38 epitopes, 144 non-epitopes). Only one representative pair was selected for detailed MD simulation, which may not capture the full diversity of binding mechanisms."},{"rthcId":"RPEP-10767","title":"Emerging Therapeutics in the Treatment of Substance Use Disorders: A Focus on GLP-1 Receptor Agonists, D3R Antagonists, and CRF Antagonists.","authors":"Draghmeh, Khaled; Fuehrlein, Brian","year":2025,"journal":"Journal of integrative neuroscience, 24(4), 26361","doi":"10.31083/JIN26361","pmid":"40302255","tags":[],"studyType":"review","evidenceStrength":"low","keyFinding":"This review examines three emerging therapeutic classes for substance use disorders: GLP-1 receptor agonists, dopamine D3 receptor antagonists, and corticotropin-releasing factor (CRF) antagonists. GLP-1 receptor agonists (like semaglutide and liraglutide) show promise in reducing alcohol and substance use by modulating the brain's reward circuitry — preclinical studies demonstrate reduced drug-seeking behavior, and early clinical observations are encouraging. CRF antagonists target the stress and relapse pathways, while D3R antagonists specifically modulate reward processing. Together, these three approaches address different stages and mechanisms of addiction: reward, stress, and relapse.","whyItMatters":"Substance use disorders affect hundreds of millions of people globally and current treatments are inadequate — approved medications exist for only a few substances (alcohol, opioids, nicotine), often with limited efficacy and significant side effects. The discovery that GLP-1 receptor agonists — drugs already widely prescribed for diabetes and obesity — may also reduce addictive behaviors opens a potentially game-changing treatment avenue. Combined with CRF and D3R-targeting approaches, a multi-pronged pharmacological strategy for addiction is emerging.","specificNumbers":"3 therapeutic classes reviewed · Targets: alcohol, opioid, and stimulant use disorders · GLP-1 RAs, D3R antagonists, CRF antagonists","methodology":"This is a narrative review of preclinical and clinical literature on three emerging therapeutic classes for substance use disorders. The authors examine evidence from animal models of addiction and available human studies for GLP-1 receptor agonists, dopamine D3 receptor antagonists, and corticotropin-releasing factor antagonists.","limitations":"Most evidence for these therapies comes from preclinical animal studies, with limited clinical trial data available. The review does not perform systematic search or meta-analysis. GLP-1 agonist effects on addiction are largely observational in humans (e.g., noticed in patients taking the drugs for other reasons), not from dedicated addiction trials. CRF antagonists have historically had disappointing clinical results despite strong preclinical data. The optimal doses, treatment durations, and patient populations for addiction applications remain undefined."},{"rthcId":"RPEP-10768","title":"Incretin-Based Therapies: A Paradigm Shift in Blood Pressure Management?","authors":"Dreher, Leonie; Kylies, Dominik; Danser, A H Jan; Wenzel, Ulrich O","year":2025,"journal":"Hypertension (Dallas, Tex. : 1979), 82(7), 1167-1174","doi":"10.1161/HYPERTENSIONAHA.125.25112","pmid":"40406862","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10769","title":"A Novel Polymersome Nanocarrier Promotes Anti-Tumour Immunity by Improved Priming of CD8 + T Cells.","authors":"Dress, Regine J; Ho, William W; Ho, Victor; Lam, Jian Hang; Décaillot, Fabien M; Sinsinbar, Gaurav; Soo, Jenetta; Rengasamy, Gowshika; Khan, Amit Kumar; Cornell, Thomas Andrew; Chia, Teck Wan; Venkataraman, Shrinivas; Nallani, Madhavan; Ginhoux, Florent","year":2025,"journal":"Immunology, 175(1), 21-35","doi":"10.1111/imm.13903","pmid":"39873184","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10770","title":"GluN2C/D-containing NMDA receptors enhance temporal summation and increase sound-evoked and spontaneous firing in the inferior colliculus.","authors":"Drotos, Audrey C; Zarb, Rachel L; Booth, Victoria; Roberts, Michael T","year":2025,"journal":"The Journal of physiology, 603(20), 6319-6343","doi":"10.1113/JP286754","pmid":"39240253","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10771","title":"GLP-1-based therapies for diabetes, obesity and beyond.","authors":"Drucker, Daniel J","year":2025,"journal":"Nature reviews. Drug discovery, 24(8), 631-650","doi":"10.1038/s41573-025-01183-8","pmid":"40281304","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10772","title":"Glucagon-like peptide-1 receptor agonist use in pregnancy: a review.","authors":"Drummond, Rosa F; Seif, Karl E; Reece, E Albert","year":2025,"journal":"American journal of obstetrics and gynecology, 232(1), 17-25","doi":"10.1016/j.ajog.2024.08.024","pmid":"39181497","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10773","title":"Assessment of noninferiority of oral vs subcutaneous semaglutide: a systematic review and meta-analysis.","authors":"Drygalski, Krzysztof; Pastuszak, Krzysztof; Modzelewska, Beata","year":2025,"journal":"Polish archives of internal medicine, 135(12)","doi":"10.20452/pamw.17141","pmid":"41117588","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10774","title":"Use and Potential Misuse of Glucagon-Like Peptide-1 Receptor Agonists in France: A Nationwide Cohort Study.","authors":"du Soulier, Nathan; Pariente, Antoine; Bezin, Julien; Grenet, Guillaume; Faillie, Jean-Luc; de Germay, Sibylle","year":2025,"journal":"Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research, 28(9), 1335-1343","doi":"10.1016/j.jval.2025.06.001","pmid":"40562309","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10775","title":"Glucagon-like peptide-1 receptor agonists and risk for cardiovascular events in older adults treated with levothyroxine: a target trial emulation.","authors":"Du, Fanxing; Ospina, Naykky M Singh; Chen, Yishan; Brito, Juan P; Liu, Qing; Schmidt, Stephan; McCoy, Rozalina G; Cicali, Brian; Shao, Hui; Jiao, Tianze","year":2025,"journal":"Cardiovascular diabetology, 24(1), 459","doi":"10.1186/s12933-025-02971-7","pmid":"41444586","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10776","title":"Applications of cell penetrating peptide-based drug delivery system in immunotherapy.","authors":"Du, Jing-Jing; Zhang, Ru-Yan; Jiang, Shangchi; Xiao, Shanshan; Liu, Yiting; Niu, Yongheng; Zhao, Wen-Xiang; Wang, Dongyuan; Ma, XianShi","year":2025,"journal":"Frontiers in immunology, 16, 1540192","doi":"10.3389/fimmu.2025.1540192","pmid":"39911386","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10777","title":"Ginseng Oligopeptides Promote Longevity and Enhance Stress Resistance in Caenorhabditis elegans via the DAF-16/FOXO Pathway.","authors":"Du, Qian; Zhang, Yiping; Guo, Xiaoyu; Cai, Meng; Li, Yong; Xu, Meihong","year":2025,"journal":"Antioxidants (Basel, Switzerland), 14(12)","doi":"10.3390/antiox14121390","pmid":"41462590","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10778","title":"Transport and action of sesame protein-derived ACE inhibitory peptides ITAPHW and IRPNGL.","authors":"Du, Tonghao; Yang, Jiahui; Qin, Yuan; Huang, Xizhuo; Li, Jiahui; Xiong, Shijin; Xu, Xiaoyan; Zhang, Linli; Zhao, Mingwei; Li, Huiyu; Huang, Tao; Xiong, Tao; Xie, Mingyong","year":2025,"journal":"Food chemistry, 472, 142965","doi":"10.1016/j.foodchem.2025.142965","pmid":"39842202","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10779","title":"Innovative Glucagon-like Peptide 1 Receptor Agonists: Exploring the Therapeutic Potential of Specific Modified Monomer, Dimer, and Tetramer in Type 2 Diabetes Treatment.","authors":"Du, Yan; Liu, Tao; Li, Hua-Lin; Luo, Qun; Guo, Xiao-Yuan; Wang, Jian-Yun; Wang, Xin-Rui; Zhou, Ya-Man; Pan, Ya-Wen; Yu, Li-Cheng; Tan, Hong-Mei; Hu, Ke-Sheng; Tang, Song-Shan","year":2025,"journal":"Bioconjugate chemistry, 36(8), 1753-1766","doi":"10.1021/acs.bioconjchem.5c00261","pmid":"40679854","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10780","title":"Cell-Penetrating Peptides in infection and immunization.","authors":"Du, Yongliang; Xiong, Yan; Sha, Zhou; Guo, Dong; Fu, Beibei; Lin, Xiaoyuan; Wu, Haibo","year":2025,"journal":"Microbiological research, 290, 127963","doi":"10.1016/j.micres.2024.127963","pmid":"39522201","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10781","title":"Medical therapy to treat obesity and optimize fertility in women of reproductive age: a narrative review.","authors":"Duah, Janelle; Seifer, David B","year":2025,"journal":"Reproductive biology and endocrinology : RB&E, 23(1), 2","doi":"10.1186/s12958-024-01339-y","pmid":"39762910","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10782","title":"Calcium and Vitamin D Supplementation with and Without Collagen on Bone Density and Skin Elasticity in Menopausal Women-A Randomized Controlled Study.","authors":"Duangjai, Acharaporn; Srivilai, Jukkarin; Nangola, Sawitree; Amornlerdpison, Doungporn","year":2025,"journal":"Clinics and practice, 15(9)","doi":"10.3390/clinpract15090168","pmid":"41002783","tags":[],"studyType":"rct","evidenceStrength":"moderate","keyFinding":"Fish-derived collagen peptides combined with calcium and vitamin D3 significantly improved skin hydration by 23% and skin elasticity by 8.52% in menopausal women after six months. Collagen alone improved elasticity by 12.23%. All active supplement groups (calcium+D3, collagen, and the combination) significantly reduced hair shedding compared to placebo.\n\nHowever, none of the supplement combinations produced significant changes in bone turnover markers (P1NP, BAP, osteocalcin) or body composition over the six-month period. Safety markers (creatinine, ALT, AST) remained normal across all groups.","whyItMatters":"Menopause causes estrogen loss that simultaneously affects bones, skin, and hair. This study tests whether a combined supplement approach can address multiple symptoms at once. While the bone benefits weren't seen in this timeframe, the significant skin and hair improvements suggest collagen peptides offer real cosmetic benefits for menopausal women.","specificNumbers":"4 groups · 6 months · Skin hydration +23% (combo group) · Skin elasticity +8.52% (combo) and +12.23% (collagen alone) · Reduced hair shedding in all active groups · No bone marker changes","methodology":"Randomized controlled trial with four groups: placebo, calcium 1000 mg + vitamin D3 400 IU, collagen peptides 5 g, and the combination of all three. Participants received daily supplementation for six months. Outcomes included body composition, bone turnover markers (P1NP, BAP, osteocalcin), skin hydration, skin elasticity, transepidermal water loss, hair loss, and safety labs.","limitations":"The sample size is not specified in the abstract, which makes it difficult to assess statistical power. Six months may be too short to detect changes in bone density or bone turnover markers. The study does not specify blinding procedures. Specific participant numbers per group are not reported."},{"rthcId":"RPEP-10783","title":"To conjugate or not to conjugate? evaluating the potential use of cell-penetrating peptides for conjugation or complexation with oligonucleotides by surface plasmon resonance.","authors":"Dueholm, Rikke; Ewald, Jakob; Zosel, Franziska; Heljo, Petteri; Premdjee, Bhavesh; Davies, Alexander; Buckley, Stephen T; Hovgaard, Lars; Nielsen, Hanne Mørck","year":2025,"journal":"International journal of pharmaceutics, 671, 125198","doi":"10.1016/j.ijpharm.2025.125198","pmid":"39793637","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10784","title":"GLP-1RA versus placebo in patients with heart failure and mildly reduced or preserved ejection fraction: An updated meta-analysis of randomized controlled trials.","authors":"Duhan, Sanchit; Kurpad, Krishna Prasad; Keisham, Bijeta; Shtembari, Jurgen; Brener, Alina; Kanakadandi, Uday B; Garg, Anuj; Adoni, Naveed A; Mehta, Sanjay S","year":2025,"journal":"International journal of cardiology, 438, 133604","doi":"10.1016/j.ijcard.2025.133604","pmid":"40623630","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10785","title":"Growth hormone-releasing hormone signaling and manifestations within the cardiovascular system.","authors":"Dulce, Raul A; Hatzistergos, Konstantinos E; Kanashiro-Takeuchi, Rosemeire M; Takeuchi, Lauro M; Balkan, Wayne; Hare, Joshua M","year":2025,"journal":"Reviews in endocrine & metabolic disorders, 26(3), 397-412","doi":"10.1007/s11154-024-09939-0","pmid":"39883351","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10786","title":"Sensory-neuron-derived CGRPα controls white adipocyte differentiation and tissue plasticity.","authors":"Dumont, Kyle D; Heydari Seradj, Saba; Wang, Yu; Liu, Shanshan; Cervenka, Igor; Wu, Chao; Jannig, Paulo R; Porsmyr-Palmertz, Margareta; Baiges-Gaya, Gerard; Huang, Xun; Nihlen, Carina; Dias, José M; Skiotyte, Simona S; Præstholm, Stine Marie; Wilbert, Dawn; Leuchtmann, Aurel B; Quinn, Melissa A; Zhu, Ziming; Hepler, Chelsea; Lundberg, Jon O; Teixeira, Ana I; Rosenzweig, Anthony; Wu, Jun; Ye, Li; Ruas, Jorge L","year":2025,"journal":"Cell reports, 44(12), 116613","doi":"10.1016/j.celrep.2025.116613","pmid":"41275495","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10787","title":"Individualized virtual integrative medicine (IVIM): A clinical model for enhanced GLP-1 therapeutic outcomes.","authors":"Duncan, Jessica; Lee Stevens, Patrick; Bigby, Emily; Floyd, Courtney; Malina, Josh; Nickens, Jennifer; Lambert, Amber; Kantor, Taylor","year":2025,"journal":"Obesity pillars, 15, 100188","doi":"10.1016/j.obpill.2025.100188","pmid":"40687923","tags":[],"studyType":"retrospective cohort","evidenceStrength":"moderate","keyFinding":"Among 1,131 patients with obesity who completed at least one year of semaglutide therapy combined with the Individualized Virtual Integrative Medicine (IVIM) protocol, the average weight loss was 19.5% of total body weight at 52 weeks. Nearly half (47.8%) lost 20% or more of their body weight, and 99.2% lost at least 5%. Weight loss followed a consistent trajectory of approximately 0.739 pounds per week (p < 0.0001). Patients who continued to 68 weeks lost an average of 21.8% of their body weight.\n\nAt milestone timepoints: 12 weeks saw 6.5% weight loss (14.9 lbs), 24 weeks 12.6% (28.6 lbs), 36 weeks 16.4% (36.8 lbs), and 52 weeks 19.5% (45.95 lbs).","whyItMatters":"Clinical trials of semaglutide typically report 15-17% weight loss at one year. This real-world study suggests that combining semaglutide with a structured integrative medicine approach — delivered via telehealth — may enhance weight loss outcomes beyond what the medication achieves alone in trials. With 99.2% of patients achieving clinically meaningful weight loss (≥5%), the results point to the potential value of comprehensive clinical support programs alongside GLP-1 therapy.","specificNumbers":"n=1,131 · 19.5% body weight loss at 52 weeks · 47.8% lost ≥20% · 99.2% lost ≥5% · -0.739 lbs/week · p<0.0001","methodology":"This retrospective analysis examined 1,131 patients with BMI ≥30 who completed at least 365 days on the IVIM protocol while taking semaglutide. Patients were prescribed individualized semaglutide therapy based on weight goals, insurance coverage, medication accessibility, and socioeconomic factors. The protocol was delivered via telehealth. A Linear Mixed Effects Model assessed the relationship between time on the protocol and weight loss.","limitations":"This is a retrospective study with no control group — there is no way to determine how much of the weight loss is attributable to semaglutide alone versus the IVIM protocol. Only patients who completed at least 365 days were included, which creates survivorship bias by excluding those who dropped out early (who may have lost less weight). The study does not detail the specific components of the IVIM protocol or what \"integrative medicine\" entailed. Dosing of semaglutide varied among patients, including during GLP-1 shortages."},{"rthcId":"RPEP-10788","title":"Persistence with once-weekly glucagon-like peptide 1 receptor agonist therapy decreases the risk of major adverse cardiovascular events: A retrospective analysis of patients with type 2 diabetes mellitus and atherosclerotic cardiovascular disease.","authors":"Dunn, Tyler J; Zhu, Yong; Gronroos, Noelle N; Xie, Lin; Sargent, Andrew; Gamble, Cory; Billings, Liana K","year":2025,"journal":"Diabetes research and clinical practice, 223, 112162","doi":"10.1016/j.diabres.2025.112162","pmid":"40220796","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 29,516 patients with type 2 diabetes and atherosclerotic cardiovascular disease who started once-weekly GLP-1 receptor agonists, those who remained persistent with therapy had significantly lower cardiovascular risks compared to non-persistent patients:\n\n- 2-point MACE (major adverse cardiovascular events): HR 0.696 (95% CI: 0.626–0.774), representing a ~30% risk reduction\n- Stroke: HR 0.668 (95% CI: 0.573–0.777), representing a ~33% risk reduction\n- Myocardial infarction (heart attack): HR 0.710 (95% CI: 0.621–0.813), representing a ~29% risk reduction\n\nAll associations were statistically significant (p < 0.001). Persistent patients were followed for an average of 418 days, while non-persistent patients were followed for 741 days.","whyItMatters":"GLP-1 receptor agonists have been shown in clinical trials to reduce cardiovascular events, but real-world medication adherence is often poor. This study quantifies the cardiovascular cost of non-persistence: patients who stop or have gaps in their GLP-1 therapy miss out on approximately 30% of the cardiovascular protection these drugs can provide. This has implications for clinical counseling and insurance coverage policies.","specificNumbers":"","methodology":"This was a retrospective cohort study using the Optum Research Database (a large US claims database). Researchers identified patients who started once-weekly GLP-1 receptor agonists between January 2018 and November 2022. Patients were classified as persistent (no gap ≥60 days in medication supply after the first 3 months) or non-persistent. Time-varying Cox proportional hazards models with adjustment for confounders assessed the association between persistence and cardiovascular outcomes.","limitations":"This is a retrospective observational study, so it cannot prove causation — patients who stay on medication may differ from those who stop in ways that independently affect cardiovascular risk (healthy adherer bias). The study used claims data, which may not capture all relevant clinical variables. Non-persistent patients had longer follow-up, which could introduce surveillance bias. Specific GLP-1 agents were not differentiated in the results."},{"rthcId":"RPEP-10789","title":"Hyperdilute Radiesse Preserves Facial Volume in Glucagon-Like Peptide-1 Receptor Agonist Users Undergoing Rapid Weight Loss.","authors":"Durairaj, K Kay; McCarthy, Alec D; Yambao, Monalea; Linnemann-Heath, Jacob","year":2025,"journal":"Aesthetic surgery journal. Open forum, 7, ojaf088","doi":"10.1093/asjof/ojaf088","pmid":"41127050","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10790","title":"Liraglutide Enhances Cell Viability and Reduces Oxidative Stress in Hyperglycemic H9c2 Cardiomyocytes.","authors":"Durmus, Sinem; Dogan, Zeki; Ergun, Dilek Duzgun; Ozdemir, Mahmut; Sahin, Hakan; Senturk, Gozde Erkanli; Gelisgen, Remise; Uzun, Hafize","year":2025,"journal":"Medicina (Kaunas, Lithuania), 61(10)","doi":"10.3390/medicina61101754","pmid":"41155741","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10791","title":"Torreya grandis nut peptides regulate lipid-II inhibitors in high-fat diet-fed mice.","authors":"Durrani, Rabia; Yutian, Sun; Bowen, Hou; Ullah, Hammad; Durand, Erwann; Meiyun, Yang; Yiyang, Long; Delavault, André; Yasir, Muhammad; Weiwei, Huan; Fei, Gao; Lili, Song","year":2025,"journal":"Food chemistry. Molecular sciences, 11, 100273","doi":"10.1016/j.fochms.2025.100273","pmid":"40704369","tags":[],"studyType":"animal","evidenceStrength":"preliminary","keyFinding":"Peptides derived from Torreya grandis nuts improved multiple metabolic markers in mice fed a high-fat diet. The supplementation reduced body weight, total cholesterol, triglycerides, and LDL while increasing HDL. Lipid droplet accumulation in the liver, muscles, and blood vessels was markedly reduced in the high-peptide group.\n\nThe peptides also favorably shifted gut microbiota composition, increasing beneficial Akkermansia and Parabacteroides while decreasing Firmicutes, which boosted short-chain fatty acid production. Proteome analysis identified a vicilin-like antimicrobial peptide, and transcriptome analysis showed lipid regulation via the PPAR-α pathway. Molecular docking identified 4 potential lipid II inhibitory peptides.","whyItMatters":"With obesity and metabolic syndrome reaching epidemic levels, food-derived bioactive peptides represent a potential dietary intervention strategy. This study provides a comprehensive multi-omics characterization of how nut-derived peptides affect lipid metabolism, gut microbiota, and gene expression — connecting peptide supplementation to multiple beneficial pathways simultaneously.","specificNumbers":"","methodology":"Mice were fed a high-fat diet with or without Torreya grandis nut peptide supplementation. Researchers used proteome analysis to identify bioactive peptides, 16S rRNA sequencing to characterize gut microbiota changes, transcriptome analysis to identify lipid regulation pathways, and molecular docking to identify potential lipid II inhibitory peptides. Blood lipids, inflammation markers, oxidative stress, and tissue lipid droplets were measured.","limitations":"This is a mouse study and results may not translate directly to humans. The specific peptide doses and treatment duration are not detailed in the abstract. The identified lipid II inhibitory peptides are based on molecular docking predictions and need experimental validation. The gut microbiota findings in mice may differ from human responses."},{"rthcId":"RPEP-10792","title":"NT-proBNP and BNP Testing in Pulmonary Arterial Hypertension: Point-of-Care and Remote Monitoring.","authors":"Durrington, Charlotte; Battersby, Christian; Holt, Laura; Fairman, Alexandra; Strickland, Scarlett; Salisbury, Thomas; Turton, Helena A; Watson, Lisa; Smith, Ian; Roman, Stefan; Ablott, Jenna; Hitchcock, Felicity; Roddis, Chloe; Oakes, Eleanor; Wilshaw, Heather; Woodrow, Iain; Armstrong, Iain; Charalampopoulos, Athanasios; Elliot, Charlie A; Hameed, Abdul; Hamilton, Neil; Hurdman, Judith A; Lawrie, Allan; Middleton, Jennifer T; Zafar, Hamza; Rothman, Alex M K; Condliffe, Robin; Lewis, Robert A; Kiely, David G; Thompson, A A Roger","year":2025,"journal":"Respirology (Carlton, Vic.), 30(11), 1094-1103","doi":"10.1111/resp.70087","pmid":"40611611","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"NT-proBNP point-of-care testing showed excellent agreement with laboratory standards:\n- Passing-Bablok analysis: slope = 1.08 (CI 0.97–1.19), intercept = 18.22 (CI -41.6 to 4.5) — indicating equivalent results\n- Intraclass correlation coefficient (ICC) = 0.97\n- POCT correctly classified 92% of cases against COMPERA 2.0 4-risk-strata thresholds\n\nBNP point-of-care testing was less reliable:\n- Passing-Bablok showed non-equivalence (slope = 1.24, CI 1.11–1.31)\n- POCT correctly classified only 86% of cases\n- BNP identified fewer high-risk patients than NT-proBNP\n- BNP and NT-proBNP risk status agreed at only 57% of visits (p < 0.0009)\n\nNT-proBNP in posted (mailed) blood samples showed good agreement with immediately processed samples. Exercise did not have a clinically significant effect on either NT-proBNP or BNP results.","whyItMatters":"PAH is a serious condition where timely monitoring can be life-saving. Currently, patients must wait for lab results that aren't available during their clinic visit, potentially delaying treatment decisions. Point-of-care testing could enable immediate clinical action, while remote monitoring via mailed samples could reduce the need for frequent hospital visits — particularly important for patients who travel long distances to specialist centers.","specificNumbers":"","methodology":"This was a prospective study enrolling 41 Group 1 PAH patients across 56 study visits. Blood samples were taken at two time points for both laboratory and point-of-care NT-proBNP and BNP testing. Separate samples were mailed back to the laboratory to test stability during postal transit, simulating remote monitoring. Some samples were assessed before and after exercise. Agreement between methods was evaluated using Passing-Bablok regression, ICC, and COMPERA 2.0 risk stratification thresholds.","limitations":"The study enrolled only 41 patients, though this met the pre-specified sample size calculation. It was conducted at a single center. The POCT device used is specific and results may vary with different devices. The postal stability testing simulated remote monitoring but actual home-based sample collection introduces additional variables. The study focused on Group 1 PAH and may not generalize to other forms of pulmonary hypertension."},{"rthcId":"RPEP-10793","title":"Efficacy and Safety of Glucagon Like Peptide-1 Receptor Agonism Based Therapies in Obstructive Sleep Apnoea: A Systematic Review and Meta-Analysis.","authors":"Dutta, Deep; Jindal, Radhika; Raizada, Nishant; Nagendra, Lakshmi; Kamrul, Hasan Abm; Sharma, Meha","year":2025,"journal":"Indian journal of endocrinology and metabolism, 29(1), 4-12","doi":"10.4103/ijem.ijem_365_24","pmid":"40181850","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10794","title":"Efficacy and Safety of Twincretin Survodutide, a Dual Glucagon-Like Peptide-1 and Glucagon Receptor Agonist as an Anti-Obesity and Anti-Diabetes Medication: A Systematic Review and Meta-Analysis.","authors":"Dutta, Deep; Kamrul-Hasan, Abul B M; Joshi, Ameya; Dhall, Anil; Nagendra, Lakshmi; Sharma, Meha","year":2025,"journal":"Indian journal of endocrinology and metabolism, 29(3), 253-259","doi":"10.4103/ijem.ijem_366_24","pmid":"40688625","tags":["glp-1-agonists","weight-management"],"studyType":"meta-analysis","evidenceStrength":"moderate","keyFinding":"This systematic review and meta-analysis pooled data from 3 randomized controlled trials involving 1,088 patients with diabetes and/or obesity. Survodutide at 2.4 mg/week produced a mean body weight reduction of 7.79% compared to placebo. HbA1c also decreased significantly.\n\nHowever, the 2.4 mg dose was associated with nearly 3 times the odds of treatment-emergent adverse events (OR 2.93) compared to placebo, though severe adverse events were not increased. Gastrointestinal side effects were the most common and were dose-dependent. Treatment discontinuation due to side effects was also significantly higher with survodutide and increased with dose. The authors concluded that the optimal dose range appears to be 2.4 to 4.8 mg/week.","whyItMatters":"Survodutide is part of the next wave of multi-agonist weight loss peptides that target both the GLP-1 and glucagon receptors simultaneously. This meta-analysis is one of the first to pool clinical trial data for survodutide, providing a clearer picture of its efficacy-safety balance. The impressive weight loss comes with a meaningful side effect burden, which will be critical to manage as the drug moves through development.","specificNumbers":"n=1,088 across 3 RCTs · -7.79% body weight at 2.4 mg · OR 2.93 for adverse events vs placebo · Follow-up: 4–11 months · Optimal range: 2.4–4.8 mg/week","methodology":"Systematic review and meta-analysis of randomized controlled trials from electronic databases. Included studies involved patients with diabetes and/or obesity receiving once-weekly subcutaneous survodutide versus placebo or active comparator. Primary outcomes were percent changes in body weight and HbA1c. Secondary outcomes included absolute weight change, blood pressure, fatty liver parameters, and adverse events.","limitations":"Only 3 RCTs were available for analysis, with follow-up ranging from just 4 to 11 months — too short to assess long-term safety or weight maintenance. There was high statistical heterogeneity (I² = 98% for weight loss), suggesting the included trials had meaningfully different results. Long-term cardiovascular outcome data and head-to-head comparisons with established GLP-1 drugs are lacking."},{"rthcId":"RPEP-10795","title":"Impact of semaglutide use on glycemic and metabolic profile in adults with type 1 diabetes having overweight or obesity: A systematic review and meta-analysis.","authors":"Dutta, Deep; Kamrul-Hasan, A B M; Jindal, Radhika; Mohindra, Ritin; Nagendra, Lakshmi; Bhattacharya, Saptarshi","year":2025,"journal":"Medicine, 104(50), e46446","doi":"10.1097/MD.0000000000046446","pmid":"41398803","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10796","title":"Substance P release from rat dura mater is inversely correlated with CGRP release- experiments using glycerol trinitrate and anti-CGRP antibodies.","authors":"Dux, Mária; Messlinger, Karl","year":2025,"journal":"The journal of headache and pain, 26(1), 119","doi":"10.1186/s10194-025-02050-y","pmid":"40380328","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10797","title":"Metabolic Modulators in Depression: Emerging Molecular Mechanisms and Therapeutic Opportunities.","authors":"Dyndał, Kinga; Pańczyszyn-Trzewik, Patrycja; Sowa-Kućma, Magdalena","year":2025,"journal":"International journal of molecular sciences, 26(17)","doi":"10.3390/ijms26178755","pmid":"40943672","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10798","title":"Impact of Reducing Obesity in PCOS: Methods and Treatment Outcomes.","authors":"Dzienny, Alexa C; Seifer, David B","year":2025,"journal":"Journal of personalized medicine, 15(11)","doi":"10.3390/jpm15110518","pmid":"41295220","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10799","title":"Long-Term Effects of Semaglutide and Sitagliptin on Circulating IGFBP-1, IGFBP-3 and IGFBP-rp1: Results from a One-Year Study in Type 2 Diabetes.","authors":"Dániel, Eszter; Sztanek, Ferenc; Csiha, Sára; Ratku, Balázs; Somodi, Sándor; Paragh, György; Harangi, Mariann; Lőrincz, Hajnalka","year":2025,"journal":"International journal of molecular sciences, 26(21)","doi":"10.3390/ijms262110404","pmid":"41226444","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10800","title":"Higher Compliance with Treatment Administration Instructions for Injectable Dulaglutide versus Oral Semaglutide Reported by People with Type 2 Diabetes in Clinical Practice Settings in Spain: The TRU-Experience Study.","authors":"Díaz-Cerezo, Silvia; Artime, Esther; Redondo-Antón, Jennifer; Duque, Natalia; Spaepen, Erik; Mangas Cruz, Miguel Ángel; Arnas-Leon, Claudia; Olveira, Gabriel; Rodríguez, Irene Rodríguez; Julián Alagarda, María Teresa; Valdés, Nuria; Merchante, Agustín Ángel; Masmiquel, Lluís; Rubio-de Santos, Miriam","year":2025,"journal":"Patient preference and adherence, 19, 1231-1244","doi":"10.2147/PPA.S509483","pmid":"40330535","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 95 dulaglutide users and 135 oral semaglutide users, compliance with all package leaflet administration instructions was 96.8% for weekly injectable dulaglutide versus 90.4% for daily oral semaglutide. After adjusting for potential between-group imbalances, the odds ratio for higher compliance with dulaglutide was 3.2 (95% CI: 1.4-21.3), indicating significantly better adherence to administration instructions.\n\nThe lower compliance with oral semaglutide is attributed to its complex administration requirements: taking it first thing in the morning on an empty stomach with no more than 120 mL of plain water, then waiting at least 30 minutes before eating, drinking, or taking other medications.","whyItMatters":"Medication compliance directly affects treatment outcomes. If patients don't take oral semaglutide correctly (especially the fasting and waiting requirements), absorption is reduced and the drug may not work as well. This real-world data helps clinicians choose between GLP-1 drug formulations based on which their patients are more likely to use correctly — not just which is theoretically more convenient.","specificNumbers":"","methodology":"Observational cross-sectional study conducted in Endocrinology Units across Spain. Patients with T2D who had been on weekly dulaglutide or daily oral semaglutide for 3-12 months were consecutively recruited during routine visits. Clinical data were extracted from medical records. An ad-hoc questionnaire assessed how often patients followed each administration instruction. Compliance was compared between groups using logistic regression with adjustment for sociodemographic and clinical imbalances.","limitations":"The wide confidence interval (1.4-21.3) suggests imprecision, likely due to the small sample size. The study was observational and cross-sectional, not randomized, so inherent differences between patients who were prescribed each drug may influence results. Self-reported compliance may overestimate actual adherence. The study was conducted in Spanish Endocrinology Units and may not generalize to primary care or other countries. The study was supported by Eli Lilly (manufacturer of dulaglutide), which is a potential conflict of interest."},{"rthcId":"RPEP-10801","title":"Subclinical Changes in Type 2 Diabetes Patients with Heart Failure Stage A and B Treated with Oral Semaglutide.","authors":"Dăniluc, Larissa; Braha, Adina; Sandu, Oana Elena; Bogdan, Carina; Suhov, Loredana; Haj Ali, Lina; Lazăr-Höcher, Alexandra-Iulia; Sima, Alexandra; Apostol, Adrian; Ivan, Mihaela Viviana","year":2025,"journal":"Medicina (Kaunas, Lithuania), 61(4)","doi":"10.3390/medicina61040567","pmid":"40282858","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10802","title":"Peptide-based strategies for overcoming taxol-resistance in cancer therapy - a narrative review.","authors":"Długosz-Pokorska, Angelika; Gach-Janczak, Katarzyna","year":2025,"journal":"Pharmacological reports : PR, 77(6), 1627-1638","doi":"10.1007/s43440-025-00795-6","pmid":"41114937","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10803","title":"Linking Metabolic Syndrome to Neurodegeneration Mechanisms and Potential Treatments.","authors":"Džidić-Krivić, Amina; Fajkić, Almir; Farhat, Esma Karahmet; Lekić, Lana; Ejubović, Amira; Vukas, Samra Kadić; Ejubović, Malik; Lepara, Orhan; Sher, Emina Karahmet","year":2025,"journal":"Molecular neurobiology, 62(11), 14344-14366","doi":"10.1007/s12035-025-04947-w","pmid":"40272771","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10804","title":"Variable GLP-1 receptor expression across diverse neuroendocrine neoplasms: implications for incretin therapies.","authors":"Ear, Po Hien; Hueser, Sophia A; Townsend, Reese E; Maxwell, Jessica E; Abusada, Ellen; Chan, Carlos H F; Quelle, Dawn E; Dillon, Joseph S; Howe, James R; Bellizzi, Andrew M","year":2025,"journal":"Endocrine oncology (Bristol, England), 5(1), e250051","doi":"10.1530/EO-25-0051","pmid":"41312422","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10805","title":"Vicarious efficacy of tirzepatide in a cohabiting couple: An observational case report.","authors":"Eason, Kieran; Feeney, Claire; Killeen, Tim","year":2025,"journal":"Obesity pillars, 16, 100219","doi":"10.1016/j.obpill.2025.100219","pmid":"41211573","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10806","title":"ToxIR: an accurate RNA-seq pipeline for high-precision toxin transcriptome profiling, validated in odontobuthus doriae venom glands.","authors":"Ebadi, Mehran; Soorki, Maryam Naderi","year":2025,"journal":"Scientific reports, 16(1), 3529","doi":"10.1038/s41598-025-33632-0","pmid":"41444383","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"ToxIR, a new RNA-seq computational pipeline, identified 378 putative toxin peptide candidates from scorpion venom glands, including 192 high-confidence candidates and 23 novel divergent toxins not previously described. The pipeline found 180 sodium channel, 111 potassium channel, and 69 chloride channel toxin peptides. ToxIR minimizes assembly errors and annotation bias through its modular design combining deep sequencing, de novo assembly, structural analysis, and curated toxin database searches.","whyItMatters":"Scorpion venom contains hundreds of bioactive peptides with potential therapeutic applications — from pain treatment to cancer therapy. However, discovering these peptides has been limited by computational tools that produce too many errors. ToxIR provides a more accurate way to catalog the full diversity of venom peptides, accelerating the discovery of new peptide drug candidates from one of nature's most complex biological libraries.","specificNumbers":"378 putative toxin candidates · 192 high-confidence (Group A) · 23 novel divergent toxins (Group C) · 180 sodium channel toxins · 111 potassium channel toxins · 69 chloride channel toxins","methodology":"ToxIR combines deep RNA sequencing of Odontobuthus doriae scorpion venom glands with rnaSPAdes-based de novo assembly, quality control (FastQC, Trimmomatic), curated UniProt toxin homology searches, and structural analyses (SignalP, TMHMM, Pfam, InterProScan). Candidates are prioritized based on signal peptides, cysteine content, and toxin-specific domains, with SQLite-backed data integration for automated analysis.","limitations":"The pipeline was validated on a single scorpion species (Odontobuthus doriae), and performance may vary with other venomous organisms. The computational predictions of toxin candidates require experimental validation of biological activity. The 'novel' toxins identified computationally need functional characterization to confirm they are actual bioactive peptides."},{"rthcId":"RPEP-10807","title":"Pitstop approach: diabetologist referral and quality of care in patients with type 2 diabetes - a Swiss longitudinal study.","authors":"Ebrahimi, Fahim; Hubacher, Simone; Christ, Emanuel; Zechmann, Stefan","year":2025,"journal":"Swiss medical weekly, 155, 4031","doi":"10.57187/s.4031","pmid":"41100838","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10808","title":"Sacubitril/valsartan versus enalapril in chronic Chagas cardiomyopathy with heart failure: Baseline characteristics of the PARACHUTE-HF trial.","authors":"Echeverria, Luis Eduardo; Bocchi, Edimar; Demacq, Caroline; de Barros E Silva, Pedro Gabriel Melo; Chiang, Lu-May; Sayyed, Sarfaraz; Damiani, Lucas Petri; Barbosa, Lilian Mazza; Furtado, Remo Holanda de Mendonça; Morillo, Carlos A; Kevorkian, Ruben; Ramires, Felix; Bahit, Maria Cecilia; Chavez-Mendoza, Adolfo; Magaña-Serrano, José Antonio; Carbajales, Justo; Oliveira Junior, Wilson; Molina, Israel; Freitas Junior, Aguinaldo F; Moreira, Maria da Consolaçao; Silva, Adegil Henrique; Silva Junior, Telemaco; Saporito, Wladimir; Kerr Saraiva, José Francisco; Gimpelewicz, Claudio; McMurray, John J V; Lopes, Renato Delascio","year":2025,"journal":"European journal of heart failure, 27(12), 2879-2886","doi":"10.1002/ejhf.70026","pmid":"40916703","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10809","title":"Targeting GLP-1 Signaling Ameliorates Cystogenesis in a Zebrafish Model of Nephronophthisis.","authors":"Eckert, Priska; Nöller, Maike; Müller, Merle; Haas, Rebecca; Ruf, Johannes; Franz, Henriette; Moos, Katharina; Yu, Jia-Ao; Zhao, Dongfang; Xie, Wanqiu; Boerries, Melanie; Walz, Gerd; Yakulov, Toma A","year":2025,"journal":"International journal of molecular sciences, 26(15)","doi":"10.3390/ijms26157366","pmid":"40806500","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A systematic drug repurposing screen in nphp1/nphp4-depleted zebrafish identified GLP-1 signaling as a novel therapeutic target for nephronophthisis. DPP-4 inhibitors (omarigliptin and linagliptin) and the GLP-1 receptor agonist semaglutide significantly reduced cystogenesis in a dose-dependent manner. Genetic analysis confirmed GLP-1 receptors (gcgra and gcgrb) are important for pronephros integrity. Transcriptomics identified adenosine receptor A2ab (adora2ab) as a key downstream effector regulating ciliary morphology. Nphp1/nphp4 double mutant zebrafish showed compensatory upregulation of GLP-1 receptor genes, and disrupting this compensation enhanced cyst formation.","whyItMatters":"Nephronophthisis has no treatment — affected children inevitably progress to kidney failure requiring dialysis or transplant. The discovery that already-approved, widely-used GLP-1 medications could potentially treat this condition is a major breakthrough. Drug repurposing from FDA-approved medications could dramatically shorten the path from discovery to clinical use, potentially helping patients within years rather than decades.","specificNumbers":"","methodology":"Researchers developed a zebrafish model of nephronophthisis by simultaneously depleting nphp1 and nphp4 genes, reproducing glomerular cyst formation. They performed a systematic drug repurposing screen testing FDA-approved medications. Hits were validated with dose-response studies. Genetic analysis using morpholinos and mutants dissected the signaling pathway. Transcriptomic profiling identified downstream effectors. GLP-1 receptor depletion and adenylate cyclase inhibition experiments confirmed the signaling cascade.","limitations":"Zebrafish kidney biology differs significantly from human kidneys, and findings may not translate directly. The pronephros (zebrafish kidney) is structurally simpler than the mammalian metanephros. No mammalian validation was performed. The screen identified pathway-level effects but clinical dosing for this indication is unknown. The compensatory GLP-1 receptor upregulation seen in mutant zebrafish may or may not occur in human NPH patients."},{"rthcId":"RPEP-10810","title":"Cardio-kidney-metabolic protective effects of semaglutide across the spectrum of chronic kidney disease.","authors":"Economos, Harry; MacIsaac, Richard J","year":2025,"journal":"World journal of nephrology, 14(4), 109457","doi":"10.5527/wjn.v14.i4.109457","pmid":"41479840","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The Evaluate Renal Function with Semaglutide Once Weekly trial demonstrated that semaglutide significantly reduced the risk of major kidney outcomes including kidney failure, death from kidney or cardiovascular causes, reduced albuminuria, and major cardiovascular events.\n\nBased on this and supporting evidence, guidelines now position semaglutide as the fourth pillar of diabetic kidney disease therapy, complementing SGLT2 inhibitors, non-steroidal mineralocorticoid receptor antagonists, and renin-angiotensin-aldosterone system blockers. The review also notes emerging evidence for kidney-protective effects in people without diabetes, and metabolic benefits not achievable with the other three standard therapies.","whyItMatters":"Chronic kidney disease affects hundreds of millions worldwide and is a leading cause of death, especially in people with diabetes. Adding semaglutide as a fourth treatment pillar — with complementary mechanisms of action — represents a significant advance in kidney disease management and may help slow progression where existing three-drug combinations are insufficient.","specificNumbers":"","methodology":"This is a narrative review summarizing clinical evidence for semaglutide's kidney-protective effects. It draws primarily from the Evaluate Renal Function with Semaglutide Once Weekly trial and other clinical trial data, examining outcomes in individuals with and without type 2 diabetes across the spectrum of chronic kidney disease.","limitations":"As a narrative review, this paper synthesizes existing evidence rather than generating new data. The evidence for kidney protection in people without diabetes is described as emerging and less established. Long-term outcomes beyond the trial follow-up periods are not yet known, and real-world effectiveness may differ from clinical trial results."},{"rthcId":"RPEP-10811","title":"An inhibitory GLP-1 circuit in the lateral septum modulates reward processing and alcohol intake in rodents.","authors":"Edvardsson, Christian E; Cadeddu, Davide; Ericson, Mia; Adermark, Louise; Jerlhag, Elisabet","year":2025,"journal":"EBioMedicine, 115, 105684","doi":"10.1016/j.ebiom.2025.105684","pmid":"40245495","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10812","title":"NPY-functionalized niosomes for targeted delivery of margatoxin in breast cancer therapy.","authors":"Eftekhari, Zohre; Chiani, Mohsen; Kazemi-Lomedasht, Fatemeh","year":2025,"journal":"Medical oncology (Northwood, London, England), 42(10), 465","doi":"10.1007/s12032-025-03026-3","pmid":"40924348","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10813","title":"Postprandial Responses to Animal Products with Distinct Fatty Acid and Amino Acid Composition Are Diet-Dependent.","authors":"Egelandsdal, Bjørg; Haug, Anna; Rehfeld, Jens F; Coutinho, Sílvia; Roglà Ricart, Lledó; Martens, Harald; Monfort-Pires, Milena; Martins, Catia","year":2025,"journal":"Nutrients, 17(9)","doi":"10.3390/nu17091581","pmid":"40362890","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10814","title":"Sex differences in migraine: bridging pathophysiology and clinical care in women.","authors":"Egodage, U K; Mohideen, M S; Mohotti, S P","year":2025,"journal":"Advances in physiology education, 49(4), 1109-1115","doi":"10.1152/advan.00020.2025","pmid":"41087022","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10815","title":"Anti-Angiogenic RNAi-Based Treatment of Endometriosis in a Rat Model Using CXCR4-Targeted Peptide Nanoparticles.","authors":"Egorova, Anna; Freund, Svetlana; Krylova, Iuliia; Kislova, Anastasia; Kiselev, Anton","year":2025,"journal":"International journal of molecular sciences, 26(21)","doi":"10.3390/ijms262110582","pmid":"41226635","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10816","title":"The modulatory effect of oat on brain-derived neurotrophic factor, orexigenic neuropeptides, and dopaminergic signaling in obesity-induced rat model: a comparative study to orlistat.","authors":"Ehab, Madonna; Omran, Nayra; Handoussa, Heba","year":2025,"journal":"Journal of the science of food and agriculture, 105(2), 1251-1262","doi":"10.1002/jsfa.13915","pmid":"39314063","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10817","title":"A new trivalent recombinant protein for type 2 diabetes mellitus with oral delivery potential: design, expression, and experimental validation.","authors":"Ehsasatvatan, Maryam; Baghban Kohnehrouz, Bahram","year":2025,"journal":"Journal of biomolecular structure & dynamics, 43(14), 7416-7431","doi":"10.1080/07391102.2024.2329290","pmid":"38468545","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10818","title":"CCR2 dependent recruited pro-inflammatory monocytes contribute to the development of left ventricular hypertrophy in mice upon transverse aortic constriction.","authors":"Eichhorn, Lars; Kleiner, Jan Lukas; Bartsch, Benedikt; Nazir, Mariam Louis Fathy; Zhang, Yunyang; Coburn, Mark; Frede, Stilla; Weisheit, Christina Katharina","year":2025,"journal":"PloS one, 20(4), e0318407","doi":"10.1371/journal.pone.0318407","pmid":"40257974","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10819","title":"OPIOID-EXPRESSING B CELLS SILENCE TUMOR-INFILTRATING NOCICEPTOR NEURONS.","authors":"Eichwald, Tuany; Ahmadi, Maryam; Matos, Andre Martel; Nikpoor, Amin Reza; Roversi, Karine; Balood, Mohammad; Obuekwe, Fendi; Nilsen, Marci L; Ruffin, Ayana T; Pinheiro, Gabryella; Brabenec, Laura; Rafei, Moutih; Vermeer, Paola; Bruno, Tullia C; Scheff, Nicole N; Talbot, Sebastien","year":2025,"journal":"Research square","doi":"10.21203/rs.3.rs-7389517/v1","pmid":"40951290","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10820","title":"Semaglutide Beyond Diabetes and Obesity: Systematic Review and Meta-Analysis of Multisystem Therapeutic Benefits.","authors":"Eisa, Naseem; Barood, Omar","year":2025,"journal":"Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists","doi":"10.1016/j.eprac.2025.11.018","pmid":"41419187","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10821","title":"Safety and Efficacy of Tirzepatide in Solid-Organ Transplant Recipients: Experience of a Quaternary Care Center in the Middle East.","authors":"El Khatib, Omar; Chiha, Maguy; Hijazi, Rabih; Jarad, Ola; Salloum, Cynthia; El Baba, Khaled; Dajani, Ruba; Al Shaqfa, Salma; El Hajj, Sandra","year":2025,"journal":"Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation, 23(1), 12-20","doi":"10.6002/ect.2024.0284","pmid":"39918190","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10822","title":"Comparing the Efficacy of Liraglutide and Semaglutide on Weight Loss: Experience from the Middle East Gulf Region and Literature Review.","authors":"El Nekidy, Wasim S; Hasan, Haneen; Abidi, Emna; Al Sayegh, Layth; Dajani, Ruba Z; El-Kaissi, Samer; Hegazin, Safa B; Mallat, Jihad","year":2025,"journal":"Hospital pharmacy, 00185787251340645","doi":"10.1177/00185787251340645","pmid":"40417637","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 366 patients (122 liraglutide, 244 semaglutide) with similar baseline characteristics (mean age ~51, mean weight ~94.6-94.7 kg):\n\n- **Weight loss**: No significant difference between liraglutide and semaglutide (P = 0.867)\n- **HbA1c reduction**: Semaglutide was significantly superior — median reduction of -0.5% vs. -0.2% for liraglutide (P = 0.003)\n- **Lipids**: Both drugs significantly lowered LDL cholesterol and triglycerides\n- **Multivariable analysis**: Confirmed no significant difference in weight loss between drugs (B -0.577, 95% CI -1.87 to 0.7; P = 0.38)\n- Baseline weight, diabetes status, and SGLT2 inhibitor use were identified as significant factors affecting weight outcomes","whyItMatters":"With multiple GLP-1 drugs now available, clinicians and patients need real-world data to guide treatment choices. While randomized trials have studied these drugs individually, head-to-head comparisons in real clinical practice are scarce. This study provides practical evidence from a Middle Eastern population — a region with high rates of obesity and diabetes — showing that the weight loss difference between these two drugs may be less dramatic than marketing suggests.","specificNumbers":"","methodology":"This was a retrospective observational cohort study conducted at a quaternary care hospital in the Middle East Gulf region from June 2018 to July 2022. Adults who received either liraglutide or semaglutide during the study period were identified from medical records. Weight loss was the primary outcome, with HbA1c and lipid changes as secondary outcomes. Multivariable linear regression was used to control for confounding factors.","limitations":"This is a retrospective observational study, not a randomized controlled trial, so it cannot establish causation and may be affected by selection bias and unmeasured confounders. The liraglutide group had a longer median follow-up (10 vs. 7.5 months), which could affect comparisons. The abstract does not report the absolute weight loss in kilograms for either group. Dosing details and adherence rates are not specified. The study comes from a single center in the Gulf region, which may limit generalizability."},{"rthcId":"RPEP-10823","title":"Sensory Symptoms as an Early Manifestation of Active Vitiligo: A Case-Control Clinical and Molecular Study.","authors":"El Sayed, Hagar; El Wakeel, Hala; Nour, Zeinab; Mohyeeldeen, Riham; Hafez, Vanessa","year":2025,"journal":"Pigment cell & melanoma research, 38(1), e13223","doi":"10.1111/pcmr.13223","pmid":"39869070","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10824","title":"Exploring novel protective role of semaglutide in 5-fluorouracil-induced hepatotoxicity: Insights into phosphorylated CREB, PINK1/Parkin-mediated mitophagy, and NF-κB/NLRP3 pathways.","authors":"El Sayed, Nermein F; Baraka, Sara A; El-Mokadem, Bassant M; El Osaily, Heba H; Bishr, Abeer","year":2025,"journal":"The Journal of pharmacology and experimental therapeutics, 392(8), 103629","doi":"10.1016/j.jpet.2025.103629","pmid":"40609293","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"5-FU administration caused marked increases in hepatic enzyme levels, oxidative stress markers (malondialdehyde), inflammatory markers (TNF-α, IL-6), and histological liver injury in rats.\n\nSemaglutide pretreatment (0.3 mg/kg orally) effectively counteracted these harmful effects through multiple pathways: it suppressed the ROS/NF-κB/NLRP3 inflammasome inflammatory cascade, reduced oxidative stress (lowering MDA while increasing glutathione), decreased apoptosis (reducing caspase-3), and activated the pCREB/Nrf2/HO-1 antioxidant signaling pathway.\n\nCritically, semaglutide enhanced PINK1/Parkin-mediated mitophagy — the process of removing damaged mitochondria. When chloroquine (an autophagy inhibitor) was co-administered with semaglutide, the protective effects were abolished, confirming that mitophagy enhancement is a key mechanism of semaglutide's hepatoprotective action.","whyItMatters":"Chemotherapy-induced liver toxicity is a significant clinical problem that can force dose reductions or treatment discontinuation in cancer patients. Finding a drug that can protect the liver during chemotherapy — without interfering with the cancer-killing effects — would be extremely valuable. Semaglutide is already widely prescribed for other conditions, so if its hepatoprotective effects translate to humans, it could be repurposed relatively quickly as a supportive care agent during chemotherapy.","specificNumbers":"","methodology":"Sprague-Dawley rats were divided into five groups: control (saline), 5-FU alone (150 mg/kg IP), semaglutide (0.3 mg/kg oral) + 5-FU, semaglutide + 5-FU + chloroquine (10 mg/kg IP, autophagy inhibitor), and 5-FU + chloroquine. Liver damage was assessed through hepatic enzyme levels, oxidative stress markers (MDA, glutathione), inflammatory markers (TNF-α, IL-6), apoptosis markers (caspase-3), and histological examination. Molecular pathways were evaluated including NF-κB/NLRP3 inflammasome, PINK1/Parkin mitophagy, and pCREB/Nrf2/HO-1 signaling.","limitations":"This is an animal study in rats using a single chemotherapy agent (5-FU) at a specific dose. The results may not translate directly to humans or to other chemotherapy drugs. The study did not assess whether semaglutide affects the anti-tumor efficacy of 5-FU — a critical question for clinical application. Semaglutide was given as pretreatment, and its protective effect when given after chemotherapy initiation is unknown. The study used a single semaglutide dose, so dose-response relationships are not established. Long-term effects and safety of combining GLP-1 agonists with chemotherapy are not addressed."},{"rthcId":"RPEP-10825","title":"A Trade-Off Between Antimicrobial Peptide Resistance and Sensitivity to Host Immune Effectors in Staphylococcus aureus In Vivo.","authors":"El Shazely, Baydaa; Rolff, Jens","year":2025,"journal":"Evolutionary applications, 18(2), e70068","doi":"10.1111/eva.70068","pmid":"39925620","tags":[],"studyType":"In Vivo Experimental Study","evidenceStrength":"moderate","keyFinding":"When Staphylococcus aureus evolves resistance to antimicrobial peptides (AMPs), it pays a hidden cost: it becomes more vulnerable to other immune defenses. Researchers found that S. aureus strains resistant to tenecin 1 (an insect AMP) showed \"collateral sensitivity\" to phenoloxidase (another immune effector) and to other AMPs in the host's defense arsenal.\n\nThis trade-off explains a paradox: AMP-resistant bacteria don't actually become more virulent in living hosts, even though they can survive exposure to individual AMPs in a test tube. In the mealworm beetle model, AMP-resistant S. aureus didn't increase host mortality or bacterial load compared to wild-type bacteria. The immune system's use of multiple, diverse antimicrobial mechanisms creates an evolutionary trap — resistance to one peptide comes at the cost of vulnerability to others.","whyItMatters":"A major concern about developing AMPs as antibiotics has been whether bacteria would quickly evolve resistance, just as they have to conventional antibiotics. This study provides reassuring evidence that AMP resistance carries built-in costs — bacteria that become resistant to one AMP become more susceptible to other immune defenses. This suggests that the immune system's strategy of deploying multiple AMPs simultaneously is inherently resistance-proof, and that therapeutic AMP cocktails might be similarly durable.","specificNumbers":"S. aureus strains resistant to tenecin 1 and tenecin 1+2 tested · All but 1 strain showed collateral sensitivity to phenoloxidase · Some strains sensitive to other AMPs · RNAi knockdown used to isolate immune effector contributions · No net virulence increase in vivo","methodology":"Researchers used S. aureus strains that had been experimentally evolved to resist insect AMPs (tenecin 1 alone or tenecin 1+2 combined). They tested these resistant strains against other immune effectors (phenoloxidase, other AMPs) in the yellow mealworm beetle (Tenebrio molitor). RNAi-based gene knockdown was used to selectively disable specific immune pathways in the host, allowing the researchers to measure how AMP-resistant bacteria survived when facing individual immune components.","limitations":"Uses an insect model (mealworm beetle), not mammalian or human immune systems. While the principles of AMP resistance trade-offs likely apply broadly, the specific immune effectors differ between insects and humans. The S. aureus strains were evolved in laboratory conditions, which may not fully reflect natural resistance evolution. The study examines a limited number of resistant strains."},{"rthcId":"RPEP-10826","title":"Antibacterial activities of novel peptide nucleic acids targeting Salmonella penicillin-binding proteins.","authors":"El-Fateh, Mohamed; Viau, Charles; Ahmed, Nada; Xia, Jianguo; Zhao, Xin","year":2025,"journal":"Molecular therapy. Nucleic acids, 36(4), 102762","doi":"10.1016/j.omtn.2025.102762","pmid":"41323793","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10827","title":"Intranasal empagliflozin modulates synaptic plasticity in migraine: Insights into calcium signaling and epigenetic regulation.","authors":"El-Mezayen, Nesrine S; Noah, Ashraf A; El-Ganainy, Samar O","year":2025,"journal":"European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 213, 107251","doi":"10.1016/j.ejps.2025.107251","pmid":"40886734","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10828","title":"Cardiovascular effects of incretin-based drugs in patients with and without a history of heart failure: a protocol for a systematic review, meta-analysis and trial sequential analysis of randomised controlled trials.","authors":"El-Sheikh, Mohammed; Sillassen, Christina Dam Bjerregaard; Wisborg, Frederik Dencker; Hove, Jens Dahlgaard; Dirksen, Carsten; Lee, Matthew Meng Yang; Jakobsen, Janus C; Grand, Johannes","year":2025,"journal":"BMJ open, 15(9), e103668","doi":"10.1136/bmjopen-2025-103668","pmid":"40976663","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10829","title":"Current perspectives on the use of GLP-1 receptor agonists in obesity-related obstructive sleep apnea: a narrative review.","authors":"El-Solh, Ali A; Gould, Erin; Aibangbee, Keziah; Jimerson, Tanya; Hartling, Rebecca","year":2025,"journal":"Expert opinion on pharmacotherapy, 26(1), 51-62","doi":"10.1080/14656566.2024.2437525","pmid":"39621418","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10830","title":"Biophysical and transcriptomic characterization of LL-37-derived antimicrobial peptide targeting multidrug-resistant Escherichia coli and ESKAPE pathogens.","authors":"Eladl, Omar","year":2025,"journal":"Scientific reports, 15(1), 36126","doi":"10.1038/s41598-025-22890-7","pmid":"41102328","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10831","title":"The GLP-1 agonist semaglutide ameliorates cognitive regression in P301S tauopathy mice model via autophagy/ACE2/SIRT1/FOXO1-Mediated Microglia Polarization.","authors":"Elbadawy, Norhan N; Saad, Muhammed A; Elfarrash, Sara; Ahmed, Maha A E; Abdelkader, Noha F","year":2025,"journal":"European journal of pharmacology, 991, 177305","doi":"10.1016/j.ejphar.2025.177305","pmid":"39875022","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10832","title":"Low Dose GLP-1 Therapy Attenuates Pathological Cardiac and Hepatic Remodelling in HFpEF Independent of Weight Loss.","authors":"Elbatreek, Mahmoud H; Li, Zhen; Yu, Xiaoman; Gehred, Natalie D; Gromova, Tatiana; Chen, Jingshu; Muraoka, Naoto; Jensen, Martin; Kartha, Vinay; Carrico, Chris; Allerton, Timothy D; Bowdish, Michael E; Chikwe, Joanna; Shah, Sanjiv J; Woulfe, Kathleen C; McKinsey, Timothy A; Yoo, Edwin; Polhemus, David J; Vondriska, Thomas M; Goodchild, Traci T; Lefer, David J","year":2025,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2025.09.26.678829","pmid":"41256540","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10833","title":"The Role of the AMY1 Receptor Signaling Cascade in the Protective Effect of Sulforaphane Against Nitroglycerin-Induced Migraine in Mice.","authors":"Elbendary, Luejine A; Abdel-Latif, Ghada A; Khattab, Mohamed A; El-Sahar, Ayman E; Sayed, Rabab H","year":2025,"journal":"Archiv der Pharmazie, 358(9), e70107","doi":"10.1002/ardp.70107","pmid":"41017172","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In female mice with nitroglycerin-induced migraine, sulforaphane (5 mg/kg/day for 9 days) showed significant improvements:\n\n- Behavioral: Reduced photophobia, head grooming, mechanical and thermal allodynia\n- Biochemical: Lowered serum nitric oxide, CGRP, and pro-inflammatory cytokines\n- Histological: Ameliorated damage in trigeminal ganglia and trigeminal nucleus caudalis\n- Molecular: Reduced AMY1 receptor expression in the medulla; inhibited downstream phospho-ERK1/2, P38, and c-Fos signaling\n- Enhanced Nrf2/HO-1 antioxidant pathway while suppressing NF-κB/NLRP3/caspase-1 inflammatory cascade\n\nEffects were comparable to the standard migraine medication topiramate (30 mg/kg/day).","whyItMatters":"The AMY1 receptor is shared by both amylin and CGRP — two peptides increasingly recognized as key players in migraine. Understanding that a natural compound can modulate this receptor pathway adds to the growing toolkit of AMY1/CGRP-targeting approaches for migraine treatment, complementing the existing antibody and gepant therapies.","specificNumbers":"","methodology":"Female mice received nitroglycerin (10 mg/kg i.p. every other day) to induce migraine. Treatment groups received sulforaphane (5 mg/kg/day i.p.) or topiramate (30 mg/kg/day i.p.) for 9 days. Behavioral testing assessed photophobia, head grooming, and allodynia. Serum markers (NO, CGRP, cytokines), histology (trigeminal ganglia and nucleus), and molecular signaling (AMY1 receptor, ERK, P38, c-Fos, Nrf2, NF-κB pathways) were analyzed.","limitations":"This is a mouse study; migraine in rodents is modeled imperfectly compared to human migraine. Sulforaphane was administered by injection, not orally, and bioavailability via different routes may vary. Only female mice were used, and while migraine is more common in women, results may differ in males. The 9-day treatment period is short for a preventive therapy assessment."},{"rthcId":"RPEP-10834","title":"Enhanced Bioactive Peptide Release from Pre-Hydrolysed Pea Protein: Impact of Pepsin Digestion on Antidiabetic and Antihypertensive Functions.","authors":"Elbira, Arig; Hernández-Álvarez, Alan Javier; Boesch, Christine","year":2025,"journal":"Foods (Basel, Switzerland), 14(19)","doi":"10.3390/foods14193306","pmid":"41097476","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Pre-hydrolysed pea protein achieved a 64% degree of hydrolysis during pepsin digestion, compared to approximately 40% for non-hydrolysed samples. The resulting peptides showed stronger inhibition of key metabolic enzymes.\n\nAfter ultrafiltration to concentrate small peptides (<10 kDa), the bioactive effects were dramatically enhanced:\n- α-amylase inhibition: up to 44.5%\n- α-glucosidase inhibition: up to 54%\n- ACE inhibition: up to 95%\n\nPeptidomic analysis identified unique peptide sequences in the pre-hydrolysed fractions, and computational modeling confirmed their bioactive potential.","whyItMatters":"Finding natural, food-derived peptides that can help regulate blood sugar and blood pressure is a growing area of nutritional science. This study shows that how plant proteins are processed significantly affects the bioactive potential of the peptides they release. The 95% ACE inhibition is particularly striking, suggesting pea-derived peptides could eventually be developed into functional foods or supplements for cardiovascular and metabolic health.","specificNumbers":"","methodology":"This was an in vitro laboratory study. Pea protein was either pre-hydrolysed with enzymes or left untreated, then subjected to simulated pepsin digestion. The resulting hydrolysates were filtered to concentrate small peptides (<10 kDa). Enzyme inhibition assays measured activity against α-amylase, α-glucosidase (both relevant to blood sugar), and ACE (relevant to blood pressure). Peptidomic analysis identified specific peptide sequences, and in silico prediction assessed their bioactive potential.","limitations":"This is entirely an in vitro study — enzyme inhibition in a test tube does not guarantee the same effects will occur in the human body. Peptides may be further broken down during intestinal digestion, absorbed poorly, or metabolized before reaching their target enzymes. The in silico predictions of bioactivity need validation in cell and animal models. No human or animal studies were conducted to confirm real-world health effects."},{"rthcId":"RPEP-10835","title":"Gradual Titration of Semaglutide Results in Better Treatment Adherence and Fewer Adverse Events: A Randomized Controlled Open-Label Pilot Study Examining a 16-Week Flexible Titration Regimen Versus Label-Recommended 8-Week Semaglutide Titration Regimen.","authors":"Eldor, Roy; Avraham, Noa; Rosenberg, Orit; Shpigelman, Miriam; Golan-Cohen, Avivit; Cukierman-Yaffe, Tali; Merzon, Eugene; Buch, Assaf","year":2025,"journal":"Diabetes care, 48(9), 1607-1611","doi":"10.2337/dc25-0690","pmid":"40673973","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10836","title":"Study of cathelicidin (LL-37) immunoexpression in the skin of vitiligo patients.","authors":"Elgarhy, Lamia Hamouda; Ramadan, Basma Ramadan Refaey; Sallam, Fersan Abd Allah; Iskandarani, Dalya Ayman; Hewedy, El-Sayed Shaaban","year":2025,"journal":"Archives of dermatological research, 317(1), 316","doi":"10.1007/s00403-025-03801-2","pmid":"39873762","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Cathelicidin (LL-37) immunohistochemical expression was significantly elevated in vitiligo patients compared to controls (p < 0.001). Lesional skin showed a mean expression score of 2.85 ± 0.67, while non-lesional skin scored 2.05 ± 0.51 — both significantly higher than control skin.\n\nCathelicidin levels in both lesional and non-lesional skin correlated significantly with the VIDA (Vitiligo Disease Activity) score (p < 0.001 and p = 0.016, respectively), linking higher LL-37 expression to more active disease.\n\nNotably, the elevated cathelicidin in apparently normal-looking skin of vitiligo patients suggests LL-37 may be involved before visible depigmentation occurs, potentially serving as a predictive biomarker for future lesion development.","whyItMatters":"Vitiligo affects about 1% of the global population, and its exact mechanisms remain incompletely understood. Identifying cathelicidin as a potential contributor to vitiligo pathogenesis could open new therapeutic avenues, particularly since LL-37 is already being studied in other autoimmune skin conditions. The finding that LL-37 is elevated even in normal-appearing skin is especially intriguing for early disease detection.","specificNumbers":"","methodology":"This was a case-control study comparing 20 vitiligo patients with 20 age- and sex-matched healthy controls. Researchers took 3 mm punch biopsies from both lesional (depigmented) and non-lesional (normal-appearing) skin of each patient, plus control skin. Samples were stained with H&E and analyzed for cathelicidin expression using immunohistochemistry. Disease activity was assessed using the VIDA score.","limitations":"The sample size was small (20 patients, 20 controls), limiting statistical power and generalizability. The study was cross-sectional, so it cannot establish whether elevated LL-37 causes vitiligo progression or is a consequence of it. The authors acknowledge that longitudinal studies are needed to confirm whether non-lesional LL-37 elevation truly predicts future lesion development."},{"rthcId":"RPEP-10837","title":"Interconnected Mechanistic Pathways, Molecular Biomarkers, and Therapeutic Approach of Oral Cancer in Patients with Diabetes Mellitus.","authors":"Elian, Viviana; Popovici, Violeta; Nicolescu, Mihnea Ioan; Nicolescu, Alexandra Maria; Aurelian, Sorina Maria; Ozon, Emma Adriana","year":2025,"journal":"Current issues in molecular biology, 47(11)","doi":"10.3390/cimb47110929","pmid":"41296433","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10838","title":"Molecular Biomarkers and Therapeutic Approach of Patients with Diabetes and Obstructive Sleep Apnea.","authors":"Elian, Viviana; Popovici, Violeta; Steriade, Alexandru Tudor; Radulian, Gabriela; Ozon, Emma Adriana; Moroșan, Elena; Musat, Madalina","year":2025,"journal":"International journal of molecular sciences, 26(20)","doi":"10.3390/ijms262010234","pmid":"41155523","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10839","title":"Emerging production techniques and potential health promoting properties of plant and animal protein-derived bioactive peptides.","authors":"Elisha, Cherise; Bhagwat, Prashant; Pillai, Santhosh","year":2025,"journal":"Critical reviews in food science and nutrition, 65(24), 4729-4758","doi":"10.1080/10408398.2024.2396067","pmid":"39206881","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10840","title":"The Potential Role of Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists and Glucose-Dependent Insulinotropic Polypeptide (GIP) Receptor Agonists in Obstructive Sleep Apnea and Obesity.","authors":"Ellberg, Charlotte C; Schwartz, Hannah; Witt, Annika; McCowen, Karen C; Fuentes, Ana Lucia; Malhotra, Atul","year":2025,"journal":"Current pulmonology reports, 14(1), 19","doi":"10.1007/s13665-025-00384-1","pmid":"40727552","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10841","title":"Treatment of Bile Acid Diarrhea With Glucagon-Like Peptide 1 Receptor Agonists: A Promising Yet Understudied Approach.","authors":"Ellegaard, Anne-Marie; Kårhus, Martin L; Winther-Jensen, Matilde; Lund, Asger B; Knop, Filip K","year":2025,"journal":"Clinical and translational gastroenterology, 16(3), e00815","doi":"10.14309/ctg.0000000000000815","pmid":"39807780","tags":[],"studyType":"review","evidenceStrength":"moderate","keyFinding":"This review highlights that a 6-week randomized controlled trial demonstrated the GLP-1 receptor agonist liraglutide was superior to colesevelam (the standard bile acid sequestrant treatment) for reducing bile acid diarrhea (BAD) symptoms. The authors review the broader literature on GLP-1 RAs for BAD, discuss potential mechanisms of action, and argue that newer, more potent GLP-1 RAs could offer even greater benefits for this underserved patient population.","whyItMatters":"Bile acid diarrhea affects millions of people but is underdiagnosed and poorly treated — current standard therapy (bile acid sequestrants) is only partially effective and poorly tolerated. Repurposing GLP-1 receptor agonist peptides for BAD would provide a new treatment option for a debilitating condition, and it represents yet another expanding indication for this blockbuster drug class beyond diabetes and obesity.","specificNumbers":"","methodology":"Narrative review of published literature on GLP-1 receptor agonists in bile acid diarrhea treatment, including the authors' own 6-week RCT comparing liraglutide to colesevelam. The review covers mechanisms of action, knowledge gaps, and the rationale for testing newer GLP-1 RAs in BAD.","limitations":"The evidence base for GLP-1 RAs in BAD is still very limited — primarily based on a single 6-week RCT. The review notes significant knowledge gaps and calls for further clinical evidence. Long-term efficacy and safety of GLP-1 RAs specifically for BAD patients (who may not have diabetes or obesity) are unknown."},{"rthcId":"RPEP-10842","title":"CGRP-Targeted Migraine Therapies in Patients With Vascular Risk Factors or Stroke: A Review.","authors":"Eller, Michael Thomas; Schwarzová, Katarína; Gufler, Lena; Karisik, Anel; Kaltseis, Katharina; Frank, Florian; Broessner, Gregor","year":2025,"journal":"Neurology, 105(2), e213852","doi":"10.1212/WNL.0000000000213852","pmid":"40537071","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10843","title":"Effects of Tesamorelin on Neurocognitive Impairment in Persons With HIV and Abdominal Obesity.","authors":"Ellis, Ronald J; Vaida, Florin; Hu, Keren; Dube, Michael; Henry, Brook; Chow, Felicia; Heaton, Robert K; Lee, Daniel; Sattler, Fred","year":2025,"journal":"The Journal of infectious diseases, 231(5), 1230-1238","doi":"10.1093/infdis/jiaf012","pmid":"39813152","tags":["growth-hormone-peptides","neuroprotection"],"studyType":"randomized-controlled-trial","evidenceStrength":"moderate","keyFinding":"In a 6-month trial of 73 people with HIV and abdominal obesity, tesamorelin (2 mg daily subcutaneous) significantly reduced waist circumference compared to standard of care (median difference -2.7 cm, p=0.015). However, while the tesamorelin group showed a trend toward improved cognitive performance (mean change 0.146, p=0.060), the between-group difference in cognition was not statistically significant (p=0.673). IGF-1 levels increased with tesamorelin but did not correlate with cognitive changes or waist circumference reduction.","whyItMatters":"Cognitive impairment affects up to half of people with HIV even when the virus is well controlled, and abdominal obesity may contribute through inflammation and hormonal changes. This trial tested whether reducing belly fat with a GHRH peptide could also improve brain function — a novel approach to HIV-associated cognitive problems. The negative cognitive result is important because it suggests that simply reducing visceral fat may not be enough to reverse established cognitive deficits.","specificNumbers":"n=73 · 3:2 randomization · 2 mg tesamorelin daily SC · 6 months · WC reduction -2.7 cm (p=0.015) · Cognitive trend p=0.060 · Between-group cognitive p=0.673","methodology":"Phase 2 randomized open-label clinical trial. 73 virally suppressed adults with HIV and abdominal obesity randomized 3:2 to tesamorelin (2 mg subcutaneous daily) or standard of care for 6 months. Primary outcome was change in neurocognitive performance. Secondary outcomes included waist circumference, mood, and daily functioning. Excluded patients with non-HIV causes of cognitive impairment, active substance use, or malignancy.","limitations":"Open-label design (no placebo) introduces potential bias. Underpowered — the study itself acknowledges insufficient statistical power. Six months may be too short for meaningful cognitive recovery. The lack of a placebo arm makes it difficult to separate treatment effects from natural variation. IGF-1 increases did not correlate with cognitive changes, questioning the proposed mechanism."},{"rthcId":"RPEP-10844","title":"GLP-1 Agonists and the Risk of Pulmonary Aspiration during Elective Upper Endoscopy: A Systematic Review and Meta-analysis.","authors":"Elmati, Praveen Reddy; Jagirdhar, Gowthami Sai Kogilathota; Qasba, Rakhtan K; Perez, Andres; Qasba, Ruman K; Bains, Yatinder; Shah, Mehul; Surani, Salim","year":2025,"journal":"The open respiratory medicine journal, 19, e18743064372550","doi":"10.2174/0118743064372550250603061720","pmid":"41036293","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10845","title":"The Long-Term Cost-Effectiveness of Oral Semaglutide Versus Lower-Cost Liraglutide in the UK.","authors":"Elnaggar, Mohamed; Mansinho, Joana Nunes; Malkin, Samuel J P; Whitaker, Joseph; Hunt, Barnaby; Glah, Divina; MacLellan, Martina; Ali, Samina","year":2025,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 16(4), 613-628","doi":"10.1007/s13300-025-01691-1","pmid":"39969755","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10846","title":"Regulatory Guidelines for the Analysis of Therapeutic Peptides and Proteins.","authors":"Elsayed, Yomnah Y; Kühl, Toni; Imhof, Diana","year":2025,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 31(3), e70001","doi":"10.1002/psc.70001","pmid":"39921384","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Peptide and protein drugs now account for approximately 25% of the global pharmaceutical market. The FDA, ICH (International Council for Harmonisation), and EMA (European Medicines Agency) have each established specific guidelines for the analysis, stability testing, and quality control of peptide and protein therapeutics. The review summarizes these frameworks and advocates for tailored bioanalytical workflows for each individual peptide or protein drug, since each has unique stability and characterization requirements.","whyItMatters":"As peptide drugs explode in popularity (from insulin to semaglutide and beyond), understanding how they're regulated ensures quality and safety. This review provides a comprehensive overview of the regulatory landscape across the three major regulatory bodies, which is essential for drug developers, compounding pharmacies, and anyone evaluating peptide drug quality.","specificNumbers":"~25% of global pharmaceutical market · Regulatory bodies: FDA + ICH + EMA · Growth since insulin approval (1921) · Physical + chemical characterization required","methodology":"Regulatory review article summarizing guidelines from the FDA, ICH, and EMA regarding the analysis, stability testing, quality control, and formulation requirements for therapeutic peptides and proteins.","limitations":"This is a review of existing regulatory frameworks, not an experimental study. Guidelines are inherently evolving documents — some details may change as regulators update requirements. The review focuses on the three major Western regulatory bodies and may not cover regulatory frameworks in other major markets (e.g., China's NMPA, Japan's PMDA) in equal depth."},{"rthcId":"RPEP-10847","title":"Liraglutide Attenuates Atorvastatin-Induced Hepatotoxicity by Restoring GLP-1R Expression and Activating Nrf2 and Autophagy Pathways in Wistar Rats.","authors":"Elsiad, Engy A; Abd El Aal, Hayat A; Salem, Hesham A; El-Yamany, Mohammed F; Rabie, Mostafa A","year":2025,"journal":"Toxics, 13(7)","doi":"10.3390/toxics13070594","pmid":"40711038","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10848","title":"Peptide-Loaded Nanoparticles: A Precision Approach to Breast Cancer Treatment.","authors":"Eltaib, Lina; Alanazi, Mashael N; Maqbool, Mudasir; Rana, Amita Joshi; Khan, Yumna; Hussain, Md Sadique","year":2025,"journal":"Current drug delivery","doi":"10.2174/0115672018398707250911054410","pmid":"41088984","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10849","title":"Rational Design of Stapled Covalent Peptide Modifiers of Oncoprotein E6 from Human Papillomavirus.","authors":"Emanuelson, Cole; Naro, Yuta; Shade, Olivia; Liu, Melinda; Khare, Sagar D; Deiters, Alexander","year":2025,"journal":"ACS chemical biology, 20(3), 746-757","doi":"10.1021/acschembio.4c00878","pmid":"40063062","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10850","title":"Impact of chemical structure, lipidation and formulation on luminal stability and intestinal absorption of GLP-1 analogues.","authors":"Emeh, Prosper; Englund, Maria; Harun, Said; Santisteban Valencia, Zulma; Revell, Jefferson; Hugerth, Andreas; Davies, Nigel; Bergström, Christel A S","year":2025,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 386, 114144","doi":"10.1016/j.jconrel.2025.114144","pmid":"40840601","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10851","title":"TEIPP-vaccination in checkpoint-resistant non-small cell lung cancer: a first-in-human phase I/II dose-escalation study.","authors":"Emmers, Mitchell; Welters, Marij J P; Dietz, Michelle V; Santegoets, Saskia J; Boekesteijn, Sanne; Stolk, Anouk; Loof, Nikki M; Dumoulin, Daphne W; Geel, Annemarie L; Steinbusch, Lauri C; Valentijn, A Rob P M; Cohen, Danielle; de Miranda, Noel F C C; Smit, Egbert F; Gelderblom, Hans; van Hall, Thorbald; Aerts, Joachim G; van der Burg, Sjoerd H","year":2025,"journal":"Nature communications, 16(1), 4958","doi":"10.1038/s41467-025-60281-8","pmid":"40436854","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10852","title":"Semaglutide and bariatric surgery induce distinct changes in the composition of mouse white adipose tissue.","authors":"Emont, Margo P; Essene, Adam L; Gulko, Anton; Bozadjieva-Kramer, Nadejda; Jacobs, Christopher; Nagesh, Soumya; Seeley, Randy J; Tsai, Linus T; Rosen, Evan D","year":2025,"journal":"Molecular metabolism, 95, 102126","doi":"10.1016/j.molmet.2025.102126","pmid":"40139440","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide and bariatric surgery (vertical sleeve gastrectomy) induce fundamentally different changes in fat tissue composition at the single-cell level. While both cause weight loss, the cellular landscape of fat tissue after each treatment differs from each other and from never-obese lean animals. Some cell populations return to a lean-like state while others persist in an obese-like configuration. This means weight-loss fat tissue retains a 'memory' of obesity that differs depending on how the weight was lost.","whyItMatters":"This study reveals that not all weight loss is the same at the cellular level. Despite similar weight reduction, semaglutide and surgery reprogram fat tissue differently — potentially explaining why weight regain patterns, metabolic improvements, and long-term outcomes differ between these approaches. Understanding these differences could help optimize treatment selection and develop combination strategies.","specificNumbers":"Single-cell atlases of mouse white adipose tissue · diet-induced obesity model · semaglutide vs vertical sleeve gastrectomy (VSG) · compared to lean and obese controls · cell-type-specific pathway analysis","methodology":"Researchers created detailed single-cell atlases of mouse white adipose tissue (WAT) across four conditions: lean, diet-induced obesity, post-semaglutide weight loss, and post-vertical sleeve gastrectomy weight loss. They analyzed cell type composition, identified which populations reverted to lean-like states versus persisting from obesity, and examined regulated pathways across conditions.","limitations":"This is a mouse study, and mouse fat tissue differs from human fat tissue in cell composition and function. The study examined a single time point after weight loss, so the temporal dynamics of cellular remodeling were not captured. Whether the distinct cellular signatures translate to different clinical outcomes in humans was not addressed. The study focused on white adipose tissue and did not examine brown fat or other metabolically relevant tissues."},{"rthcId":"RPEP-10853","title":"Phosphorodiamidate Morpholino Oligomers-Loaded Nanobubbles for Ultrasound-Mediated Delivery to the Myocardium in Muscular Dystrophy.","authors":"Endo-Takahashi, Yoko; Sakurai, Akane; Oguri, Yukiko; Katagiri, Fumihiko; Akiyama, Saki; Sashida, Sanae; Yamaguchi, Taiki; Marunouchi, Tetsuro; Suzuki, Ryo; Maruyama, Kazuo; Tanonaka, Kouichi; Nomizu, Motoyoshi; Negishi, Yoichi","year":2025,"journal":"ACS omega, 10(9), 9639-9648","doi":"10.1021/acsomega.4c10896","pmid":"40092813","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10854","title":"Trends in Glucagon-Like Peptide-1 Agonist Use and BMI Among Obese Adults With Type 2 Diabetes: Analysis of the 2010-2015 National Ambulatory Medical Care Survey (NAMCS), Adjusted for Cardiovascular Comorbidity.","authors":"Eneh, Victoria; Chatelain, Naomi F; Okobi, Okelue E; Okorigba, Efeturi M; Chukwuebuni, Ugochukwu P; Okahia, Tochukwu W; Bampoh, Rita A; Fanegan, Edamisan J; Ubajaka, Chioma C; Afolayan, Adebola Y; Arifayan, Sunday O; Ijeomah, Kenechukwu","year":2025,"journal":"Cureus, 17(8), e90054","doi":"10.7759/cureus.90054","pmid":"40951131","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10855","title":"The involvement of the endogenous opioid system in binge eating, food devaluation and food reward in mice.","authors":"Era, Iffat Hasnin; Hamid, Abdul; Lutfy, Kabirullah","year":2025,"journal":"Progress in neuro-psychopharmacology & biological psychiatry, 142, 111539","doi":"10.1016/j.pnpbp.2025.111539","pmid":"41138901","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Using knockout mice, the study distinguished the roles of two opioid peptides:\n\n- Mu-opioid receptor (MOR) knockout mice: reduced binge eating on high-fat diet re-exposure, diminished food devaluation after 7-day HFD exposure, and failed to show conditioned food reward\n- Beta-endorphin (β-END) knockout mice: reduced binge eating and diminished food reward, but normal food devaluation\n- Enkephalin (ENK) knockout mice: no significant changes in binge eating, food reward, or food devaluation\n\nAll genotypes showed normal initial food intake for both regular chow and high-fat diet, indicating these peptides specifically affect binge/reward behaviors rather than basic hunger.","whyItMatters":"Binge eating disorder affects millions of people and has limited pharmacological treatment options. Identifying beta-endorphin as the specific opioid peptide driving binge eating and food reward, distinct from enkephalin, provides a precise molecular target for developing treatments that could reduce pathological overeating without broadly disrupting the opioid system.","specificNumbers":"","methodology":"Male knockout mice lacking either mu-opioid receptors, beta-endorphin, or enkephalin were compared with their wildtype littermates. They were tested for regular and high-fat diet intake, binge eating (measured on re-exposure to HFD after abstinence), food reward (conditioned place preference with HFD), and food devaluation (reduced chow intake after HFD exposure).","limitations":"The study was conducted in male mice only; female mice, who have higher rates of binge eating disorders in humans, were not tested. Genetic knockouts eliminate the peptide from birth, which may trigger compensatory mechanisms not present in adult pharmacological interventions. The high-fat diet model may not fully capture the complexity of human binge eating disorder."},{"rthcId":"RPEP-10856","title":"An HIV-1 gp41 peptide-liposome vaccine elicits neutralizing epitope-targeted antibody responses in healthy individuals.","authors":"Erdmann, Nathaniel; Williams, Wilton B; Walsh, Stephen R; Cain, Derek W; Clark, Matthew; Tuck, Ryan; Holmes, Sommer; Clardy, Benae; Foulger, Andrew; Parks, Robert; Barr, Margaret; Eaton, Amanda; Saunders, Kevin O; Grunenberg, Nicole; Edlefsen, Paul; Goepfert, Paul A; Cohen, Kristen W; Maenza, Janine; Mayer, Kenneth; Van Tieu, Hong; Sobieszczyk, Magdalena E; Swann, Edith; Lu, Huiyin; De Rosa, Stephen C; Sagawa, Zachary K; Lin, Bob C; Carrol, Robin E; McKee, Krisha; Doria-Rose, Nicole A; Louder, Mark K; Moody, M Anthony; Fox, Christopher B; Ferrari, Guido; Edwards, Robert J; Acharya, Priyamvada; Alam, S Munir; Tomaras, Georgia D; Montefiori, David C; Gilbert, Peter B; McElrath, M Juliana; Corey, Lawrence; Haynes, Barton F; Baden, Lindsey R","year":2025,"journal":"medRxiv : the preprint server for health sciences","doi":"10.1101/2024.03.15.24304305","pmid":"38562833","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10857","title":"Effect of 1,25-dihydroxy vitamin D3 on inflammation, antimicrobial peptide, and D-dimer levels in Escherichia coli-induced sepsis in neonatal calves.","authors":"Eren, Emre; Aktaş, Mustafa Sinan","year":2025,"journal":"Veterinary immunology and immunopathology, 285, 110963","doi":"10.1016/j.vetimm.2025.110963","pmid":"40466521","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10858","title":"Investigation of endocrine and cerebral response and nutrition and physical performance parameters according to bigorexia nervosa levels: a cross-sectional study in sports sciences faculty students.","authors":"Erkılıç, Ali Ozan; Bayraktar, Bülent; Erkiliç, Tuğçe Orkun; Türkmen, Mutlu; Kul, Murat; Yönal, Mehmet","year":2025,"journal":"Scientific reports, 15(1), 43989","doi":"10.1038/s41598-025-27706-2","pmid":"41286328","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 120 sports science students (63 females, 57 males, ages 18-25), males scored significantly higher on the Muscle Dysmorphic Disorder Inventory than females. Salivary asprosin levels were significantly higher in males compared to females. The study found associations between bigorexia nervosa levels and endocrine markers (asprosin, GLP-1) as well as the cerebral marker BDNF, though no significant correlation was found between BMI and GLP-1 or BDNF levels (p>0.05).\n\nThe average MET value was 4.53, indicating moderate-intensity physical activity across participants. The study suggests bigorexia nervosa influences physiological and hormonal responses beyond just behavioral patterns.","whyItMatters":"Bigorexia nervosa is an increasingly recognized but understudied condition, especially among fitness-oriented young adults. Understanding its hormonal underpinnings — including effects on metabolic peptides like GLP-1 and asprosin — could help identify biomarkers for the condition and develop targeted interventions. This is one of the first studies to examine the endocrine-cerebral axis in relation to muscle dysmorphia.","specificNumbers":"","methodology":"This cross-sectional study enrolled 120 university sports science students (18-25 years). Participants completed the Muscle Dysmorphic Disorder (Bigorexia) Inventory, a food frequency questionnaire, and a demographic questionnaire via face-to-face interviews. Physical activity was assessed using the 6-Minute Walk Test with MET calculations. Saliva samples were analyzed for asprosin, GLP-1, and BDNF using ELISA. Data were analyzed with chi-square, t-test, Pearson correlation, and ANOVA.","limitations":"This is a cross-sectional study, so it cannot determine whether hormonal differences cause or result from bigorexia nervosa. The sample was limited to sports science students, who may not represent the general population. Salivary hormone measurement is less established than blood measurement for these markers. The sample size of 120 is relatively small for subgroup analyses. The abstract does not report specific effect sizes for the hormone-bigorexia associations."},{"rthcId":"RPEP-10859","title":"The Bounce-Back Effect: What Happens After Cessation of Low-Dose Semaglutide in People with HIV.","authors":"Erlandson, Kristine M; Kitch, Douglas W; Kantor, Amy; Belaunzaran-Zamudio, Pablo F; Brown, Todd T; Fichtenbaum, Carl J; Heath, Sonya L; Sattler, Fred; Lake, Jordan E","year":2025,"journal":"Clinical infectious diseases : an official publication of the Infectious Diseases Society of America","doi":"10.1093/cid/ciaf652","pmid":"41299212","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10860","title":"Botulinum toxin as an effective rescue treatment after failure of anti-CGRP monoclonal antibodies in chronic migraine patients.","authors":"Ermanis, Giovanni; Tereshko, Yan; Belgrado, Enrico; Lettieri, Christian; Gigli, Gian Luigi; Valente, Mariarosaria","year":2025,"journal":"Toxicon : official journal of the International Society on Toxinology, 268, 108605","doi":"10.1016/j.toxicon.2025.108605","pmid":"41043602","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10861","title":"Nanogels conjugated with cell-penetrating peptide as drug delivery vehicle for treating urinary tract infections.","authors":"Escobedo, Humberto D; Zawadzki, Nicholas; Till, James K A; Vazquez-Torres, Andres; Wang, Guankui; Simberg, Dmitri; Orlicky, David J; Johnson, Joshua; Guess, Marsha K; Nair, Devatha P; Schurr, Michael J","year":2025,"journal":"Nanomedicine : nanotechnology, biology, and medicine, 65, 102812","doi":"10.1016/j.nano.2025.102812","pmid":"40024488","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10862","title":"Effects of grape seed extract supplementation on inflammatory biomarkers, oxidative stress, clinical symptoms, and quality of life in patients with migraine: A double-blinded randomized placebo-controlled clinical trial.","authors":"Eshaghian, Niloofar; Sadeghi, Omid; Foroghi, Aliakbar; Khorvash, Fariborz; Askari, Gholamreza","year":2025,"journal":"Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences, 30, 65","doi":"10.4103/jrms.jrms_742_25","pmid":"41623439","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10863","title":"Effects of glucagon-like peptide-1 receptor agonists on alcohol consumption: a systematic review and meta-analysis.","authors":"Eshraghi, Reza; Ghadimi, Delaram J; Montazerinamin, Sara; Bahrami, Ashkan; Kachela, Yash; Rezasoltani, Mahsa; Namazi, Mohammad Javad; Subhani, Mohsan; Ebrahimi, Pouya; Hosseini, Kaveh","year":2025,"journal":"EClinicalMedicine, 90, 103645","doi":"10.1016/j.eclinm.2025.103645","pmid":"41324012","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10864","title":"Oxytocin Neuropeptide in the Control of Drug Dependence: A Review of Past Studies and Future Challenges.","authors":"Esmaili-Shahzade-Ali-Akbari, Peyman; Bozorgnia, Arshia; Shaterian, Mohammad; Jandaghian, Samiya; Moghimi Shahri, Samaneh","year":2025,"journal":"The European journal of neuroscience, 62(1), e70197","doi":"10.1111/ejn.70197","pmid":"40639928","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10865","title":"Preoperative Glucagon-Like Peptide-1 Receptor Agonists and Bariatric Surgery Outcomes: A Systematic Review.","authors":"Esparham, Ali; Sheikhbahaei, Erfan; Anari Moghadam, Hengameh; Khorgami, Zhamak","year":2025,"journal":"Obesity surgery, 35(9), 3939-3946","doi":"10.1007/s11695-025-08137-4","pmid":"40782272","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 11 observational studies, preoperative GLP-1 receptor agonist use enhanced weight loss before metabolic and bariatric surgery, allowing patients to reach surgical eligibility sooner. The drugs were associated with improved diabetes outcomes post-surgery.\n\nHowever, preoperative GLP-1 RA use was linked to increased postoperative nausea. There were no significant differences in major complication rates or readmissions. Some studies noted higher surgical adhesion rates. Findings on postoperative weight loss specifically were inconsistent across studies.","whyItMatters":"GLP-1 receptor agonists have become enormously popular for weight loss, and many patients now arrive for bariatric surgery already taking these drugs. Understanding how preoperative use affects surgical outcomes is critical for surgeons and patients making treatment decisions. This review provides early evidence that the combination is generally safe, though more research is needed.","specificNumbers":"","methodology":"The researchers conducted a systematic review by searching four major medical databases (Web of Science, Embase, PubMed, and Scopus) for studies examining preoperative GLP-1 receptor agonist use before metabolic and bariatric surgery. They identified and analyzed 11 observational studies evaluating the effects on surgical outcomes.","limitations":"All 11 included studies were observational, limiting the strength of causal conclusions. Findings on postoperative weight loss were inconsistent. The review does not report pooled quantitative effect sizes. Specific GLP-1 RA drugs, doses, and treatment durations likely varied across studies, making direct comparisons difficult."},{"rthcId":"RPEP-10866","title":"Semaglutide-Induced Silent Aspiration: An Unrecognised Cause of Organising Pneumonia.","authors":"Essilfie-Quaye, Kobina; Maule, Geran; Hashim, Husham; Khraisat, Mohammad; Okonoboh, Peters; Jantz, Michael","year":2025,"journal":"Respirology case reports, 13(7), e70249","doi":"10.1002/rcr2.70249","pmid":"40625884","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10867","title":"Tumor suppressor protein-inspired peptide for siRNA delivery and synergistic cancer therapy.","authors":"Essola, Julien Milon; Yang, Haiyin; Liu, Wenjing; Hussain, Abid; Naeem, Abid; He, Huining; Barth, Stefan; Wang, Zhuoran; Fan, Kelong; Zhang, Mengjie; Zhu, Mengliang; Liang, Xing-Jie; Huang, Yuanyu","year":2025,"journal":"Fundamental research, 5(5), 1920-1929","doi":"10.1016/j.fmre.2025.03.006","pmid":"41613447","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10868","title":"Semaglutide restores astrocyte-vascular interactions and blood-brain barrier integrity in a model of diet-induced metabolic syndrome.","authors":"Estato, Vanessa; Obadia, Nathalie; Chateaubriand, Paulo Henrique; Figueiredo, Vivian; Curty, Marcela; Costa Silva, Mariana; Ferreira, Renata Gabriela Lustosa; Santa-Ritta, Juliane; Campos Baroni, Marcela; Aragão, Alessandra; Neno, João Oliveira Góes; Vasconcellos, Clara Avelar Mendes; Costa D'Avila, Joana; Gomes Granja, Marcelo; Caire de Castro Faria-Neto, Hugo","year":2025,"journal":"Diabetology & metabolic syndrome, 17(1), 2","doi":"10.1186/s13098-024-01528-0","pmid":"39754250","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10869","title":"Novel Tissue-Specific Multifunctionalized Nanotechnological Platform Encapsulating Riluzole Against Motor Neuron Diseases.","authors":"Esteruelas, Gerard; Ettcheto, Miren; Haro, Isabel; Herrando-Grabulosa, Mireia; Gaja-Capdevila, Núria; Gomara, Maria Jose; Navarro, Xavier; Espina, Marta; Souto, Eliana B; Camins, Antoni; García, Maria Luisa; Sánchez-López, Elena","year":2025,"journal":"International journal of nanomedicine, 20, 2273-2288","doi":"10.2147/IJN.S479819","pmid":"40007904","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10870","title":"US Real-World Effectiveness, Tolerability, and Healthcare Resource Utilization After Addition of Fremanezumab for Preventive Treatment in Patients Using Gepants for Acute Treatment of Migraine: Results From a Retrospective Chart Review.","authors":"Eugeni, Patrick; Rooney, Megan E; Saikali, Nicolas P; Niu, Zhongzheng; Driessen, Maurice T; Krasenbaum, Lynda J; Carr, Karen; Seminerio, Michael J; McVige, Jennifer W","year":2025,"journal":"Advances in therapy, 42(2), 1207-1221","doi":"10.1007/s12325-024-03063-w","pmid":"39775579","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10871","title":"Analysis of Tirzepatide Acquisition Costs and Weight Reduction Outcomes in the United Kingdom: Insights from the SURMOUNT-1 Study.","authors":"Evans, Marc; Evans, William; Godbeer, Fiona; Edgar, Laurienne; Spaepen, Erik; Davies, Alun Lloyd","year":2025,"journal":"Advances in therapy, 42(6), 2821-2832","doi":"10.1007/s12325-025-03194-8","pmid":"40251452","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10872","title":"Sacubitril/Valsartan vs ACE Inhibitors or ARBs: A Systematic Review and Meta-Analysis of Randomized Trials.","authors":"Evbayekha, Endurance; Idowu, Abiodun Benjamin; LaRue, Shane","year":2025,"journal":"JACC. Advances, 4(3), 101598","doi":"10.1016/j.jacadv.2025.101598","pmid":"39970741","tags":[],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"In a meta-analysis of 14 randomized trials (25,167 patients), sacubitril/valsartan reduced heart failure rehospitalization by 15% compared to ACE inhibitors or ARBs regardless of ejection fraction (RR: 0.85; P=0.00001). All-cause mortality was reduced by 12% but only in patients with ejection fraction ≤40% (RR: 0.88; P=0.0006) — no mortality benefit was seen in patients with higher ejection fractions. Notably, cardiovascular mortality was not significantly reduced in any ejection fraction group.","whyItMatters":"Sacubitril/valsartan works by blocking neprilysin — the enzyme that breaks down natriuretic peptides — allowing these protective peptides to remain active longer. This meta-analysis clarifies which heart failure patients benefit most: those with reduced ejection fraction get both fewer hospitalizations and lower mortality, while those with preserved ejection fraction only get fewer hospitalizations. This distinction helps clinicians target the drug to the right patients.","specificNumbers":"14 trials · n=25,167 · HF rehospitalization: RR 0.85, P=0.00001 · All-cause mortality (EF≤40%): RR 0.88, P=0.0006 · All-cause mortality (EF>40%): RR 0.97, P=0.67 · CV mortality: RR 0.90, P=0.13 (NS)","methodology":"Systematic review and meta-analysis of randomized clinical trials comparing sacubitril/valsartan to ACE inhibitors or ARBs. Databases searched: PubMed, EMBASE, Scopus, Cochrane Central Register (inception to November 2023). Random effects model used. Risk ratios with 95% CI reported. Heterogeneity assessed with I² test. Publication bias assessed via funnel plots and Egger test. Registered in PROSPERO (CRD42024497661).","limitations":"Results for cardiovascular mortality did not reach statistical significance, which may reflect insufficient power for this specific endpoint. The EF>40% subgroup showed no mortality benefit, but fewer trials may have been available in this population. Individual trial designs and populations varied across the 14 included studies."},{"rthcId":"RPEP-10873","title":"Amphibian-Derived Cathelicidin-DM and Cathelicidin-BG: Recombinant Overexpression in Escherichia coli and Comparison of Their Structures and Antimicrobial Activities.","authors":"Ezema, Chinonso Anthony; Shibagaki, Mitsuki; Kikukawa, Takashi; Arai, Tatsuya; Aizawa, Tomoyasu","year":2025,"journal":"ACS omega, 10(21), 21875-21888","doi":"10.1021/acsomega.5c01923","pmid":"40488015","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10874","title":"Mechanism of Semaglutide in MASLD Treatment: Where Is the Master Key?","authors":"Ezhilarasan, Devaraj","year":2025,"journal":"Journal of gastroenterology and hepatology, 40(9), 2163-2175","doi":"10.1111/jgh.17037","pmid":"40538007","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10875","title":"Sustained Action of Imapextide, a Glucagon-Like Peptide-1 Receptor Antagonist, in Healthy Volunteers.","authors":"Fabbrini, Elisa; Koshkina, Anastasiya; Hackett, Michael; Zhao, Michael; Thalluri, Kishore; Hompesch, Marcus; Macias, Alejandra; Schneider, Kristi; D'Alessio, David A; DiMarchi, Richard D; Azoulay, Salomon","year":2025,"journal":"The Journal of clinical endocrinology and metabolism","doi":"10.1210/clinem/dgaf691","pmid":"41437319","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In this Phase 1 trial, 69 healthy volunteers received imapextide at various doses (10-200 mg single dose; 10-30 mg weekly for 4 weeks) or placebo. The drug demonstrated dose-proportional exposure with a median time to peak concentration of 24-48 hours and a mean half-life of approximately 90 hours, supporting once-weekly administration.\n\nThe most common side effects were injection site reactions (erythema and swelling). During mixed meal tolerance tests, imapextide increased GLP-1 concentrations at early time points and slightly accelerated gastric emptying. Drug-drug interaction studies showed minimal, non-clinically relevant interaction with rosuvastatin. These findings support further development for post-bariatric hypoglycemia treatment.","whyItMatters":"Post-bariatric hypoglycemia is a serious complication of weight-loss surgery that currently has no approved drug treatment — patients rely mainly on dietary changes and glucose monitoring. As bariatric surgery becomes more common, the need for effective pharmacotherapy grows. Imapextide represents a novel approach: rather than adding more GLP-1 activity (as most peptide drugs do), it blocks it, addressing the excessive insulin release that causes dangerous blood sugar drops.","specificNumbers":"","methodology":"This was a 3-part, double-blind, placebo-controlled Phase 1 study in healthy adults. Part 1 (single ascending dose) tested subcutaneous imapextide at 10-200 mg. Part 2 (multiple ascending dose) tested 10-30 mg weekly for 4 doses. Part 3 assessed drug-drug interactions. Participants were randomized 3:1 to imapextide or placebo. Safety, pharmacokinetics, and pharmacodynamic responses during mixed meal tolerance tests were measured.","limitations":"This study was conducted in healthy volunteers, not in patients with post-bariatric hypoglycemia, so the therapeutic efficacy for the target condition remains unproven. Effects on glycemic parameters during meal tests were variable, and the study was not powered to assess clinical efficacy. The sample size was small (69 total across all cohorts). Longer-term safety data beyond 4 weekly doses is not yet available."},{"rthcId":"RPEP-10876","title":"Tirzepatide alters oncogenic signaling pathways in colorectal cancer cells in vitro.","authors":"Fadhil, Nasrin M; Kadhim, Jawad Hasan; Atwan, Hatham W; Alwan, Huda A; Atwan, Zeenah W","year":2025,"journal":"Cellular and molecular biology (Noisy-le-Grand, France), 71(11), 119-124","doi":"10.14715/cmb/2025.71.11.15","pmid":"41351362","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10877","title":"Can Dual Incretin Receptor Agonists Exert Better Cardiovascular Protection than Selective GLP-1 Receptor Agonists? Highlights from SURPASS-CVOT.","authors":"Fadini, Gian Paolo","year":2025,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 16(10), 1893-1898","doi":"10.1007/s13300-025-01784-x","pmid":"40886230","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"SURPASS-CVOT compared tirzepatide to dulaglutide (not placebo) for major adverse cardiovascular events (MACE) in type 2 diabetes. Tirzepatide demonstrated noninferiority with an HR of 0.92 (95.3% CI: 0.83–1.01, P = 0.086), but superiority over dulaglutide was narrowly missed. Against an imputed placebo, tirzepatide showed a potential 28% MACE risk reduction.\n\nNotably, tirzepatide achieved substantially better metabolic outcomes — 0.8% greater HbA1c reduction and 7% more weight loss than dulaglutide — yet this translated to only modest incremental cardiovascular benefit. Exploratory analyses showed promising signals for reduced mortality and better kidney function, but these require cautious interpretation. The disconnect between dramatic metabolic improvements and limited extra heart protection is the central finding of this commentary.","whyItMatters":"This raises a fundamental question for metabolic medicine: if dramatically better weight loss and blood sugar control don't proportionally improve heart outcomes, have we reached the limit of what incretin-based drugs can do for cardiovascular protection? With billions being invested in triple and multi-agonist drugs, the answer has enormous implications for drug development strategy and patient care priorities.","specificNumbers":"","methodology":"This is an expert commentary/editorial analyzing the results of the SURPASS-CVOT trial. SURPASS-CVOT was a large cardiovascular outcomes trial that used an active comparator design (tirzepatide vs dulaglutide) rather than a placebo-controlled design, reflecting the ethical reality that placebo-controlled trials are no longer appropriate when effective treatments exist. The commentary also discusses an imputed placebo analysis to estimate the absolute cardiovascular benefit of tirzepatide.","limitations":"This is a commentary by a single author, not a primary research study. The SURPASS-CVOT trial used an active comparator rather than placebo, making it harder to demonstrate superiority since dulaglutide itself provides cardiovascular benefits. The imputed placebo analysis is a statistical estimation, not a direct comparison. The commentary notes that exploratory findings on mortality and kidney function should be interpreted cautiously."},{"rthcId":"RPEP-10878","title":"Effectiveness of oral semaglutide versus empagliflozin for the management of type 2 diabetes. PIONEER-2 trial emulation with real-world data.","authors":"Fadini, Gian Paolo; Longato, Enrico; Poletto, Sara; Giaccari, Andrea; Ghiani, Mariangela; Strazzabosco, Marco; Trombetta, Maddalena; Penno, Giuseppe; Avogaro, Angelo; Solini, Anna; Consoli, Agostino","year":2025,"journal":"Diabetes, obesity & metabolism, 27(12), 7431-7440","doi":"10.1111/dom.70151","pmid":"40990044","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10879","title":"Type 2 diabetes remission after initiation of GLP-1 receptor agonists: frequency, characteristics, and outcomes using multiple definitions in an observational study.","authors":"Fadini, Gian Paolo; Giaccari, Andrea; Broglio, Fabio; Nollino, Laura; Fattor, Bruno; Anichini, Roberto; Meregalli, Giancarla; Avogaro, Angelo; Consoli, Agostino","year":2025,"journal":"The Lancet regional health. Europe, 59, 101499","doi":"10.1016/j.lanepe.2025.101499","pmid":"41142657","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10880","title":"Semaglutide and GLP-1 Agonists: Forensic and Medicolegal Implications.","authors":"Fagiola, Michael","year":2025,"journal":"The American journal of forensic medicine and pathology, 46(3), 222-228","doi":"10.1097/PAF.0000000000001044","pmid":"40261091","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies several forensic challenges posed by semaglutide and other GLP-1 agonists:\n\n- Semaglutide's large, highly charged molecular structure makes it difficult to detect and quantify using standard forensic laboratory instrumentation\n- The drug may have limited stability in whole blood samples, further complicating post-mortem analysis\n- Side effects relevant to forensic cases include hypoglycemia (which can impair driving and other performance), drug-drug interactions, and potential contribution to unexpected fatalities\n- Off-label use and misuse for weight loss expand the population potentially affected\n- No robust analytical methods currently exist for routine forensic toxicology casework involving semaglutide","whyItMatters":"Millions of Americans now take semaglutide, yet forensic laboratories cannot reliably test for it. This creates a blind spot in medicolegal investigations: if semaglutide-induced hypoglycemia causes a car crash or contributes to a death, the drug's involvement may never be identified. As off-label and unregulated weight-loss use expands, the forensic significance of this detection gap grows.","specificNumbers":"","methodology":"This is a narrative review examining the pharmacokinetics, side effects, drug interactions, and analytical challenges of semaglutide from a forensic medicine perspective. The author synthesized available pharmacological literature with forensic toxicology considerations.","limitations":"This is a brief narrative review by a single author, not a systematic analysis. No new experimental data are presented. The review focuses primarily on semaglutide and may not fully address analytical challenges of other GLP-1 RAs. Specific case examples linking semaglutide to forensic outcomes are not provided. The extent to which semaglutide actually contributes to impaired driving or fatalities is unknown."},{"rthcId":"RPEP-10881","title":"Comparative safety and side effects of semaglutide and tirzepatide: Implications for clinical decision-making in obesity management.","authors":"Fahim, Sally A; Attia, Yasmin M; Messiha, Albeir; Nabawy, Ashrakat Y; Refaat, Fady; El-Maadawy, Walaa H","year":2025,"journal":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 193, 118731","doi":"10.1016/j.biopha.2025.118731","pmid":"41177120","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Both semaglutide and tirzepatide share common side effects including gastrointestinal issues (nausea, vomiting, pancreatitis, diarrhea), bone remodeling changes, kidney disorders, and thyroid concerns. However, tirzepatide was preferred over semaglutide based on fewer reported side effects overall.\n\nTirzepatide showed additional advantages: it promoted bone formation (a protective effect) and demonstrated renal protective effects, specifically in decreasing albuminuria and slowing estimated glomerular filtration rate (eGFR) decline — markers of kidney disease progression. These advantages may be related to the additional GIP receptor activation that tirzepatide provides beyond GLP-1 agonism alone.","whyItMatters":"With tens of millions of patients prescribed these peptide drugs globally — and many expected to take them for years or indefinitely — understanding their comparative long-term safety is critical. This review provides clinicians with a side-by-side comparison to inform drug selection, particularly for patients with pre-existing bone, kidney, or thyroid conditions who may benefit from the additional protective properties of tirzepatide's dual-receptor mechanism.","specificNumbers":"","methodology":"Narrative review examining post-marketing safety data, clinical trial reports, and published literature on the long-term tolerability and side effect profiles of semaglutide and tirzepatide in obesity management.","limitations":"As a narrative review, the comparison is qualitative rather than based on a formal meta-analysis. Post-marketing safety data can be subject to reporting bias. The relative novelty of tirzepatide (approved more recently than semaglutide) means less long-term safety data is available. Head-to-head randomized safety trials would provide more definitive comparative data. Different dosing ranges and patient populations across studies complicate direct comparison."},{"rthcId":"RPEP-10882","title":"Decoding incretin resistance: a mechanistic framework to reclassify therapeutic variability for GLP-1 receptor agonist therapy.","authors":"Fajkić, Almir; Lam, Yun Wah; Belančić, Andrej","year":2025,"journal":"Amino acids, 57(1), 55","doi":"10.1007/s00726-025-03488-9","pmid":"41236578","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10883","title":"Growth hormone in disease and treatment (Review).","authors":"Fakir, Saikat; Sarker, Md Matiur Rahman; Sigdel, Madan; Barabutis, Nektarios","year":2025,"journal":"Medicine international, 5(6), 77","doi":"10.3892/mi.2025.276","pmid":"41221256","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10884","title":"Treatment Intensification Strategies and Metabolic Outcomes in Individuals With Type 2 Diabetes on GLP-1 RA Therapy.","authors":"Falcetta, Pierpaolo; Zilich, Rita; Baccetti, Fabio; Baronti, Walter; Masi, Davide; Morviducci, Lelio; Musacchio, Nicoletta; Muselli, Marco; Ozzello, Alessandro; Rossi, Antonio; Salomone, Enrica; Verda, Damiano; Vezenkova, Maria; Candido, Riccardo; Ponzani, Paola","year":2025,"journal":"The Journal of clinical endocrinology and metabolism, 110(12), e4101-e4110","doi":"10.1210/clinem/dgaf229","pmid":"40199481","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10885","title":"Pre-immunization of diet-induced obese male mice with inactivated pathogens increases power in a liraglutide intervention study.","authors":"Falkenberg, Caroline; Sørensen, Dorte B; Hansen, Camilla Hf; Toft, Martin F; Hansen, Axel K","year":2025,"journal":"Laboratory animals, 59(2), 203-214","doi":"10.1177/00236772241279058","pmid":"39696895","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10886","title":"The hypothalamic effects of PACAP on the hypothalamic-pituitary-gonadal axis in male mice.","authors":"Faludi, Péter; Barabás, Klaudia; Lengyel, Ferenc; Udvarácz, Ildikó; Pham, Dániel; Kisjós, Olivér; Nagy, Zsuzsanna; Reglődi, Dóra; Kovács, Gergely","year":2025,"journal":"Frontiers in endocrinology, 16, 1677085","doi":"10.3389/fendo.2025.1677085","pmid":"41347138","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In PACAP knockout male mice, GnRH neuron numbers and immunoreactivity were reduced in the medial preoptic area. Paradoxically, kisspeptin neuron numbers were elevated in both the RP3V and arcuate nucleus, along with increased estrogen receptor alpha (ERα) expression. The medial preoptic area showed fewer androgen receptor-positive cells but more ERα-positive cells, suggesting a disrupted balance between estrogenic and androgenic signaling. These neuroendocrine changes likely underlie the reproductive dysfunction observed in PACAP-deficient males.","whyItMatters":"Male infertility affects millions worldwide, and the brain's hormone control center is often overlooked as a contributing factor. This study reveals that a single neuropeptide — PACAP — plays a significant role in maintaining the delicate balance of reproductive signaling in the male brain, opening new avenues for understanding and potentially treating neuroendocrine causes of male infertility.","specificNumbers":"","methodology":"Researchers used PACAP knockout (KO) mice and wild-type controls. They performed immunofluorescent staining, immunohistochemistry, and RNAscope in situ hybridization to detect protein and mRNA expression of GnRH, kisspeptin, estrogen receptor alpha (ERα), and androgen receptor (AR) in the hypothalamus across key reproductive brain regions (MPOA, RP3V, arcuate nucleus).","limitations":"This is a knockout mouse study, which shows what happens when PACAP is completely absent — a more extreme scenario than reduced PACAP levels in humans. The study is observational (describing changes in KO mice) without interventional rescue experiments to confirm causality. Sample sizes were not specified in the abstract. Human relevance of these specific hypothalamic changes needs confirmation."},{"rthcId":"RPEP-10887","title":"Liraglutide inhibits the proliferation of rat hepatic stellate cells under high glucose conditions by suppressing the ERK signaling pathway.","authors":"Fan, Bingge; Meng, Lingbing; Zheng, Xiao; Bai, Lei; Du, Yaping; Ding, Haiyan; Chen, Yu; Zhang, Yuna","year":2025,"journal":"Scientific reports, 15(1), 13360","doi":"10.1038/s41598-025-97872-w","pmid":"40246983","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10888","title":"The Frog Skin-Derived Antimicrobial Peptide Suppresses Atherosclerosis by Modulating the KLF12/p300 Axis Through miR-590-5p.","authors":"Fan, Fan; Li, Meng-Miao; Qiu, Zhong-Peng; Li, Zhen-Jia; Shang, De-Jing","year":2025,"journal":"International journal of molecular sciences, 26(23)","doi":"10.3390/ijms262311497","pmid":"41373654","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The antimicrobial peptide C-1b(3-13) from frog skin suppressed atherosclerosis through a specific molecular mechanism: it upregulated miR-590-5p, which directly targeted and inhibited KLF12 expression, reducing nuclear p300 accumulation and subsequently blocking NF-κB inflammatory signaling.\n\nIn ox-LDL-induced foam cells, miR-590-5p significantly suppressed pro-inflammatory cytokine secretion. In ApoE-/- atherosclerosis mice, C-1b(3-13) treatment markedly reduced aortic plaque formation, improved lipid metabolism, suppressed inflammatory responses, and shifted macrophage polarization (reducing pro-inflammatory CD68+ M1 macrophages within plaques). The full signaling axis was validated through miRNA sequencing, dual-luciferase reporter assays, and RNA immunoprecipitation.","whyItMatters":"Atherosclerosis is the underlying cause of most heart attacks and strokes, the leading causes of death worldwide. Current treatments primarily manage risk factors (cholesterol, blood pressure) rather than directly targeting plaque inflammation. Discovering that a natural antimicrobial peptide can suppress atherosclerotic inflammation through a previously unknown mechanism opens a new therapeutic avenue. The detailed molecular pathway (miR-590-5p → KLF12 → p300 → NF-κB) provides multiple potential drug targets.","specificNumbers":"","methodology":"In vitro: miRNA sequencing identified miR-590-5p changes in ox-LDL-induced PMA-THP-1 foam cells treated with C-1b(3-13). Cytokine secretion was measured by ELISA. Target validation used dual-luciferase reporter and RIP-qPCR assays. Western blots assessed KLF12, p300, and NF-κB pathway proteins. In vivo: ApoE-/- mice (an established atherosclerosis model) were treated with C-1b(3-13). Plaque formation was assessed by Oil Red O and H&E staining of aortic roots. Macrophage distribution was analyzed by immunohistochemistry for CD68+ (M1) and CD206+ (M2) markers.","limitations":"This is entirely a preclinical study — cell culture and mouse model data that cannot be directly extrapolated to human atherosclerosis. ApoE-/- mice develop atherosclerosis differently than humans. The peptide's pharmacokinetics (absorption, stability, distribution) in humans are unknown. The study does not address potential off-target effects of systemic miR-590-5p upregulation. Dose-response relationships and optimal dosing schedules are not detailed in the abstract."},{"rthcId":"RPEP-10889","title":"Effect of Semaglutide on C-peptide levels in patients with type 2 diabetes.","authors":"Fan, Pengxiang; Ma, Xiaojun","year":2025,"journal":"Pakistan journal of pharmaceutical sciences, 38(2), 457-461","doi":null,"pmid":"40501244","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 80 hospitalized type 2 diabetes patients, semaglutide (added to metformin) produced significantly better glycemic control than insulin aspart after three months. The semaglutide group achieved lower fasting blood glucose (6.13±0.68 vs. control, P<0.05) and 2-hour postprandial glucose (9.01±0.53 mmol/L vs. control, P<0.05). Patients on semaglutide reached target blood glucose faster (3.88±0.69 days vs. 5.73±1.01 days, P<0.05). Beyond glucose control, semaglutide lowered endothelin-1 (a vasoconstrictor), improved flow-mediated vasodilation (FMD), and improved insulin resistance as measured by HOMA-IR. C-peptide levels — a marker of the pancreas's own insulin production — were also assessed as part of the metabolic panel.","whyItMatters":"This study adds to the evidence that semaglutide does more than lower blood sugar. The improvements in vascular function (lower ET-1, higher FMD) suggest cardiovascular benefits beyond glycemic control. The faster time to target glucose is clinically meaningful for hospitalized patients. It also provides comparative data against a standard insulin regimen.","specificNumbers":"n=80 · FBG 6.13±0.68 mmol/L · 2h-PBG 9.01±0.53 mmol/L · Target glucose in 3.88 vs 5.73 days · 3-month follow-up","methodology":"Prospective controlled study of 80 hospitalized T2DM patients (January 2022–December 2023). All patients received oral metformin. The control group added subcutaneous insulin aspart; the observation group added subcutaneous semaglutide. Outcomes measured at baseline and 3 months included fasting blood glucose, 2-hour postprandial glucose, time to target glucose, serum endothelin-1, flow-mediated dilation, fasting C-peptide, fasting insulin, and HOMA-IR.","limitations":"Relatively small sample size of 80 patients. Single-center study with hospitalized patients, which may not reflect outpatient populations. The abstract does not specify whether randomization was used. Published in a lower-impact journal. Three-month follow-up is relatively short for assessing long-term metabolic and vascular outcomes."},{"rthcId":"RPEP-10890","title":"Hispidulin Isolated from the Leaves of Clerodendrum inerme (L.) Gaertn Suppresses Trigeminovascular System Activation in a Rat Model Mimicking Migraine.","authors":"Fan, Pi-Chuan; Lee, Ming Tatt; Lai, Tzu-Hsuan; Huang, Wei-Jan; Chiou, Lih-Chu","year":2025,"journal":"Pharmaceutical research, 42(6), 1035-1045","doi":"10.1007/s11095-025-03864-w","pmid":"40346415","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10891","title":"Effect of the glucagon-like peptide-1 receptor agonists on diabetic peripheral neuropathy: A meta-analysis.","authors":"Fan, Shujin; Qiu, Yue; Liu, Jing; Zhu, Tianxin; Wang, Chuan; Liu, Dan; Yan, Li; Ren, Meng","year":2025,"journal":"Journal of neurochemistry, 169(2), e16242","doi":"10.1111/jnc.16242","pmid":"39453834","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10892","title":"GLP-1 as a regulator of sepsis outcomes: Insights into cellular metabolism, inflammation, and therapeutic potential.","authors":"Fan, Weixuan; Zhang, Qiulei; Wang, Cong; Sun, Jian; Zhang, Jingxiao; Yin, Yongjie","year":2025,"journal":"International immunopharmacology, 152, 114390","doi":"10.1016/j.intimp.2025.114390","pmid":"40068523","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10893","title":"Vasoactive Intestinal Peptide: A Neuropeptide that Plays an Important Role in Parkinson's Disease.","authors":"Fan, Wenhui; Li, Ke; Wang, Ruohua; Chen, Rongsha; Liu, Yiben; Yang, Zhongshan; Zhao, Ninghui; Yan, Jinyuan","year":2025,"journal":"Current neuropharmacology","doi":"10.2174/011570159X374501250425045109","pmid":"40353414","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10894","title":"Peptide-Bound Aflibercept Eye Drops for Treatment of Neovascular Age-Related Macular Degeneration in Nonhuman Primates.","authors":"Fan, Xingyan; Jiang, Kuan; Zhao, Yongqian; Lee, Benjamin Tk; Geng, Feiyang; Brelen, Marten E; Lu, Weiyue; Wei, Gang","year":2025,"journal":"Advanced science (Weinheim, Baden-Wurttemberg, Germany), 12(11), e2410744","doi":"10.1002/advs.202410744","pmid":"39888276","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10895","title":"The safety, tolerability, pharmacokinetics and pharmacodynamics of an optimized dual GLP-1/GIP receptor agonist (BGM0504) in healthy volunteers: A dose-escalation Phase I study.","authors":"Fan, Yuxin; Yuan, Jiandong; Dong, Lichun; Yu, Chongjing; Ding, Haifeng; Xie, Daosheng; Guan, Runfang; Li, Ruixia; Zou, Wenhong; Long, Shuxian; Chen, Jion; Huang, Yu; Yang, Mei; He, Jianchang; Wen, Weibo","year":2025,"journal":"Diabetes, obesity & metabolism, 27(4), 2110-2119","doi":"10.1111/dom.16203","pmid":"39840511","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10896","title":"GLP-1 Agonist Use Among Men With Localized Prostate Cancer: A Narrative Review and Rationale for Prospective Clinical Trials.","authors":"Fang, Andrew; Frigo, Daniel E; Hahn, Andrew; Razouki, Zayd; Hwang, Jessica; Koutroumpakis, Efstratios; Lawen, Tarek; Smith, Matthew; Hamilton-Reeves, Jill; DiGiovanni, John; Higgason, Noel; Garcia, Rebekka S; Chapin, Brian F; Pettaway, Curtis; Chery, Lisly; Troncoso, Patricia; Logothetis, Christopher; Daniel, Carrie R; Wei, Peng; Gregg, Justin R","year":2025,"journal":"Urology, 201, 152-158","doi":"10.1016/j.urology.2025.04.056","pmid":"40348027","tags":[],"studyType":"review","evidenceStrength":"preliminary","keyFinding":"This narrative review synthesizes epidemiologic evidence suggesting that GLP-1 receptor agonist use may be associated with decreased prostate cancer risk. The authors examine how lifestyle interventions affect men with prostate cancer, the relationship between GLP-1 RA use and prostate cancer risk, and potential mechanisms of action on tumor biology. The review provides the rationale for a planned prospective clinical trial evaluating GLP-1 RA effects on prostate cancer.","whyItMatters":"Prostate cancer is the most common cancer in men, and obesity is a known risk factor for aggressive disease. If GLP-1 receptor agonists — already widely prescribed for diabetes and obesity — also reduce prostate cancer risk or progression, it could represent an important secondary benefit for millions of men already taking these peptide drugs.","specificNumbers":"","methodology":"Narrative review of epidemiologic data on GLP-1 receptor agonist use and prostate cancer risk, combined with mechanistic exploration of how these peptide drugs could affect tumor biology. The review also defines metabolic changes in men with prostate cancer following lifestyle intervention and provides rationale for a prospective clinical trial.","limitations":"This is a narrative review presenting a rationale for future research, not a systematic review or meta-analysis. The epidemiologic association between GLP-1 RA use and reduced prostate cancer risk is observational and subject to confounding. No clinical trial results are reported — the trial is planned but not yet completed."},{"rthcId":"RPEP-10897","title":"From Phytochemistry to Metabolic Regulation: The Insulin-Promoting Effects of Loureirin B Analogous to an Agonist of GLP-1 Receptor.","authors":"Fang, Haowen; Sun, Xiaodong; Ding, Yanting; Gu, Siyuan; Niu, Bing; Chen, Qin","year":2025,"journal":"International journal of molecular sciences, 26(23)","doi":"10.3390/ijms262311548","pmid":"41373699","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10898","title":"GLP-1 and GIP: Magic bullet for musculoskeletal diseases?","authors":"Fang, Qihang; Li, Gan; Liu, Pei; Ding, Peng; Gao, Youshui","year":2025,"journal":"Journal of advanced research","doi":"10.1016/j.jare.2025.08.046","pmid":"40865632","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10899","title":"Glucagon-like peptide-1 medicines in neurological and psychiatric disorders.","authors":"Fang, Susanna; Cui, Fiona; Drucker, Daniel J","year":2025,"journal":"Cell reports. Medicine, 6(12), 102511","doi":"10.1016/j.xcrm.2025.102511","pmid":"41406951","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10900","title":"Risk of Acute Pancreatitis and Biliary Events After Initiation of Incretin-Based Medications in Patients With Type 2 Diabetes.","authors":"Fang, Yichen E; Paik, Julie M; Ortega-Montiel, Janinne; Tesfaye, Helen; Wexler, Deborah J; Patorno, Elisabetta","year":2025,"journal":"Diabetes care, 48(12), 2127-2137","doi":"10.2337/dc25-1840","pmid":"41144235","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10901","title":"Hormonal adaptations to weight loss: Responses to an oral glucose load 4 weeks after obesity surgery and low-energy diet.","authors":"Fanni, Giovanni; Hukema, Fleur; Hetty, Susanne; Mathioudaki, Argyri; Sundbom, Magnus; Risérus, Ulf; Kullberg, Joel; Pereira, Maria J; Ahlström, Håkan; Eriksson, Jan W","year":2025,"journal":"Diabetes, obesity & metabolism, 27(9), 4836-4846","doi":"10.1111/dom.16526","pmid":"40521749","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10902","title":"GLP-1 Agonist Use Leads to Earlier Return of Bowel Function Following Lumbar Fusion.","authors":"Fano, Adam; Oris, Robert J; Dalton, Jonathan; Baidya, Joydeep; Ng, Mitchell; Baek, Gregorio; Tarawneh, Omar; Narayanan, Rajkishen; Huang, Rachel; Olson, Jarod; Herczeg, Chloe; Lee, Yulia; Sellig, Mason; Chua, Theresa; Barksdale, Nicholas; Quiana, Sebastian; Ponna, Anish; Cronk, Regan; Canseco, Jose; Hilibrand, Alan; Vaccaro, Alexander; Kepler, Christopher; Schroeder, Gregory","year":2025,"journal":"Spine","doi":"10.1097/BRS.0000000000005598","pmid":"41400023","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10903","title":"GLP-1 Receptor Agonists Initiation and Risk of Acute Pancreatitis and Pancreatic Cancer: A Real-World Comparative Study.","authors":"Faour, Omar; Boktor, Moheb; Yau, Hanford; Kinaan, Mustafa; Mansi, Ishak A","year":2025,"journal":"American journal of medicine open, 14, 100114","doi":"10.1016/j.ajmo.2025.100114","pmid":"41473903","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10904","title":"Pattern of semaglutide prescription in a real-world Canadian patient cohort.","authors":"Farahvash, Armin; Lee, Michelle Cm; Jain, Rahul; Jaakkimainen, Liisa","year":2025,"journal":"Primary care diabetes, 19(5), 512-516","doi":"10.1016/j.pcd.2025.06.006","pmid":"40562647","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10905","title":"Evaluating Weight Loss Associated with Bariatric Surgery After Liraglutide Use: A Matched Population-Level Retrospective Cohort Study.","authors":"Faran, Muhammad; O'Callaghan, Emma K; McKechnie, Tyler; Barlow, Karen; Kuszaj, Olivia; Tarride, Jean-Éric; Anvari, Mehran; Doumouras, Aristithes G","year":2025,"journal":"Obesity surgery, 35(9), 3676-3685","doi":"10.1007/s11695-025-08054-6","pmid":"40711700","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10906","title":"Charting New Territories in Obesity Management- Traditional Techniques to Tirzepatide.","authors":"Fareed, Areeba; Ghanem, Laura; Vaid, Rayyan; Iftikhar, Zoha; Ur Rehman, Adeel; Sarwar, Ayesha; Asif, Muhammad Iqbal","year":2025,"journal":"Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists, 31(1), 102-113","doi":"10.1016/j.eprac.2024.09.004","pmid":"39278353","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10907","title":"A2 Milk: The Impact of Genetic Variation in Milk Protein on Human Health.","authors":"Farhat, Leila Ben; Selmi, Hiba; Toth, Violetta; Hoarau, Amanda; Suli, Agnes; Labas, Kata Sara; Ferid, Abidi; Miko, Edit","year":2025,"journal":"Current protein & peptide science, 26(9), 751-760","doi":"10.2174/0113892037366987250401183000","pmid":"40277101","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10908","title":"Urine Measurements of the Renin-Angiotensin System-Regulated Proteins Predict Death and Graft Loss in Kidney Transplant Recipients Enrolled in a Ramipril versus Placebo Randomized Controlled Trial.","authors":"Farkona, Sofia; Kotlyar, Max; Burns, Kevin; Knoll, Greg; Brinc, Davor; Jurisica, Igor; Konvalinka, Ana","year":2025,"journal":"Journal of proteome research, 24(4), 2040-2052","doi":"10.1021/acs.jproteome.4c01100","pmid":"40111290","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10909","title":"Metformin-Enhanced Digital Therapeutics for the Affordable Primary Prevention of Diabetes and Cardiovascular Diseases: Advancing Low-Cost Solutions for Lifestyle-Related Chronic Disorders.","authors":"Farley, Brian; Radetich, Emi; DAlessandro, Joseph; Bulaj, Grzegorz","year":2025,"journal":"Healthcare (Basel, Switzerland), 13(24)","doi":"10.3390/healthcare13243220","pmid":"41464289","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10910","title":"Glucagon-like peptide-1 receptor agonists, but not dipeptidyl peptidase-4 inhibitors, reduce alcohol intake.","authors":"Farokhnia, Mehdi; Tazare, John; Pince, Claire L; Bruns, Nicolaus; Gray, Joshua C; Lo Re, Vincent; Fiellin, David A; Kranzler, Henry R; Koob, George F; Justice, Amy C; Vendruscolo, Leandro F; Rentsch, Christopher T; Leggio, Lorenzo","year":2025,"journal":"The Journal of clinical investigation, 135(9)","doi":"10.1172/JCI188314","pmid":"40048376","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1RA recipients showed significantly greater reductions in AUDIT-C drinking scores compared to both unexposed individuals (DiD: 0.09, P=0.0025) and DPP-4I recipients (DiD: 0.11, P=0.0002). The effects were dramatically larger in people with baseline alcohol use disorder (GLP-1RA vs DPP-4I: DiD 0.65, P<0.0001) and hazardous drinking (GLP-1RA vs DPP-4I: DiD 1.00, P<0.0001).\n\nDPP-4 inhibitor recipients showed no difference from unexposed individuals. Animal experiments confirmed this: neither linagliptin nor omarigliptin reduced binge-like drinking in mice or alcohol self-administration in alcohol-dependent rats, despite successfully lowering blood glucose — confirming target engagement. This convergent human-animal evidence indicates the alcohol-reducing effect requires direct GLP-1 receptor agonism.","whyItMatters":"Alcohol use disorder affects millions of people and has very few effective medications. This is among the strongest evidence to date that GLP-1 drugs could be repurposed for AUD treatment. The finding that DPP-4 inhibitors don't work — despite also raising GLP-1 levels — is mechanistically important: it tells us the alcohol-reducing effect requires pharmacological-level receptor activation, not just modest increases in endogenous GLP-1.","specificNumbers":"","methodology":"The study combined a large retrospective cohort analysis using 2008-2023 VA electronic health records with reverse translational animal experiments. The human component compared propensity-score-matched groups of GLP-1RA recipients, DPP-4I recipients, and unexposed individuals using changes in AUDIT-C scores. The animal component tested two DPP-4 inhibitors (linagliptin and omarigliptin) in established mouse binge-drinking and rat alcohol self-administration models.","limitations":"The human component is observational (not a randomized trial), so confounding factors may influence results despite propensity-score matching. AUDIT-C is a self-reported measure of drinking, which can be subject to reporting bias. The VA population is predominantly male and older, which may limit generalizability. The study could not determine optimal GLP-1RA dosing for alcohol reduction or whether the effect persists after stopping the medication."},{"rthcId":"RPEP-10911","title":"Portal vein thrombosis in a patient on semaglutide.","authors":"Farooqi, Mohammed F; Khan, Maria; Arshad, Muhammad; Agha, Adnan","year":2025,"journal":"Qatar medical journal, 2025(2), 57","doi":"10.5339/qmj.2025.57","pmid":"40792243","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10912","title":"INDIVIDUAL ARTICLE: A Scientific Approach to Defining, Evaluating, and Treating Pre-Aging With a Cosmetic Regimen Containing a Novel Cosmetic Peptide, Acetyl Dipeptide-31 Amide (AP31).","authors":"Farris, Patricia; Frey, Cheri; Parsa, Ramine; Miller, Dara; Shyr, Thomas; Li, Wen-Hwa","year":2025,"journal":"Journal of drugs in dermatology : JDD, 24(5), 51181s4-51181s14","doi":"10.36849/JDD.51181","pmid":"40327583","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The study yielded several key findings across multiple experiments:\n\n- Clinical evaluation of 180 subjects identified the earliest aging signs as uneven skin tone, fine lines, and roughness, with aging turning points in the mid-twenties for lighter skin types and mid-thirties for darker skin types\n- Younger skin cells produced more reactive oxygen species (ROS) after UV exposure but were also more responsive to treatment\n- Acetyl dipeptide-31 amide (AP31) demonstrated anti-inflammatory effects and stimulated production of extracellular matrix components including collagen and elastin in vitro\n- A 12-week clinical study of 46 patients showed that a regimen containing AP31, sunscreen, and bakuchiol significantly improved early aging signs and reduced skin glycation index\n- Elasticity loss begins in the 20s and collagen content decreases progressively with age","whyItMatters":"Cosmetic peptides are a rapidly growing category in skincare, but many lack clinical evidence. This study provides both mechanistic data (how AP31 works at the cellular level) and clinical proof (that it improves aging signs in real patients). The concept of 'pre-aging' intervention — treating skin before significant damage occurs — represents a preventive approach that could preserve skin quality longer than waiting to treat established aging.","specificNumbers":"","methodology":"This was a multi-part study: (1) clinical evaluation of 180 subjects across all Fitzpatrick Skin Types to identify pre-aging features; (2) in vitro studies comparing young and old dermal fibroblasts' responses to UVA exposure and treatments; (3) in vitro evaluation of AP31's effects on inflammation and extracellular matrix production; (4) a 12-week clinical study of 46 patients with mild to moderate photoaging testing a regimen containing AP31, sunscreen, and bakuchiol. Skin glycation index was assessed via UV-fluorescence and cross-polarized imaging.","limitations":"The clinical study included only 46 patients and lasted 12 weeks — a relatively short period for assessing anti-aging benefits. The regimen combined AP31 with sunscreen and bakuchiol, making it difficult to isolate AP31's specific contribution to the observed improvements. The study was published in a dermatology journal and may have industry involvement (common for cosmetic ingredient studies). Long-term safety and efficacy data are not available. In vitro effects on fibroblasts don't always predict clinical outcomes."},{"rthcId":"RPEP-10913","title":"Omnidirectional 3D Printing of Anisotropic Nanofibrous Peptide Hydrogels.","authors":"Farsheed, Adam C; Makhoul, Jonathan T; Chew-Martinez, Danielle; Maldonado, Eros; Liu, Justin; Yu, Le Tracy; Gorostieta-Salas, Elisa; Jones, Jeffrey R; Gage, Fred H; Hartgerink, Jeffrey D","year":2025,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2025.11.06.687046","pmid":"41278881","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10914","title":"Glucagon-like peptide-1 receptor agonists to improve cardiorenal outcomes: data from FLOW and beyond.","authors":"Faruque, Labib; Yau, Kevin; Cherney, David Z I","year":2025,"journal":"Current opinion in nephrology and hypertension, 34(3), 232-240","doi":"10.1097/MNH.0000000000001066","pmid":"40047207","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10915","title":"Evaluation of N-terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) as a Biomarker of Cardiac Dysfunction Across Heart Failure Phenotypes.","authors":"Fatima, Ambreen; Haris Mansoor, Makhdoom; Munir, Ahsan; Ali, Bilawal; Maryam, Hamna; Tariq, Muhammad Salman","year":2025,"journal":"Cureus, 17(11), e96447","doi":"10.7759/cureus.96447","pmid":"41384195","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10916","title":"Pro-endometriosis macrophage release of IL-33 is key for endometriosis pain and lesion formation.","authors":"Fattori, Victor; Rasquel-Oliveira, Fernanda S; Ochoa, Soledad; Graf, Eva; Bazzano, Maria V; Aung, Thiha; Vural, Mehmet; Kohl, Cynthia; Solano, Maria E; da Silva, Matheus D V; Heintz, Olivia K; Brierley, Stuart M; Verri, Waldiceu A; Haerteis, Silke; Castro, Joel; Lawrenson, Kate; Rogers, Michael S","year":2025,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2025.10.20.683510","pmid":"41279884","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10917","title":"Survival Benefits of GLP-1 Receptor Agonists in Patients with Neuroendocrine Neoplasms: A Large-Scale Propensity-Matched Cohort Study.","authors":"Fawzy, Manal S; Alenezy, Awwad; Jishu, Jessan A; Khan, Issa; Dessouky, Ahmad; Abdelmaksoud, Ahmed; Limbach, Kristen E; Toraih, Eman A","year":2025,"journal":"Cancers, 17(9)","doi":"10.3390/cancers17091593","pmid":"40361517","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10918","title":"Assessment of cardiac biomarker \"point-of-care\" testing as postmortem diagnostic tool.","authors":"Federspiel, Jan Michael; Kettner, Mattias; Potente, Stefan; Heinbuch, Sara; Lux, Constantin; Verhoff, Marcel A; Ramsthaler, Frank","year":2025,"journal":"International journal of legal medicine, 139(5), 2577-2591","doi":"10.1007/s00414-025-03517-y","pmid":"40439936","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10919","title":"Downstream interaction by glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide agonism is required for synergistic effects on body weight.","authors":"Feetham, Claire H; Ai, Minrong; Culotta, Isabella; Costa, Alessia; Hunter, Jenna; Brown, Robert A; Coskun, Tamer; Emmerson, Paul J; D'Agostino, Giuseppe; Luckman, Simon M","year":2025,"journal":"Molecular metabolism, 99, 102214","doi":"10.1016/j.molmet.2025.102214","pmid":"40681104","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10920","title":"A fish-specific antimicrobial peptide MsPiscidin2 inactivates MSRV and confers protection in largemouth bass.","authors":"Fei, Chenjie; Wang, Ziwen; Hu, Yang; Nie, Li; Chen, Jiong","year":2025,"journal":"Frontiers in immunology, 16, 1629256","doi":"10.3389/fimmu.2025.1629256","pmid":"40625750","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10921","title":"What the diabetologist needs to know about the risk of non-arteritic anterior ischaemic optic neuropathy and GLP-1 receptor agonist use in patients with type 2 diabetes.","authors":"Feldman-Billard, Sylvie","year":2025,"journal":"Diabetes & metabolism, 51(4), 101664","doi":"10.1016/j.diabet.2025.101664","pmid":"40383371","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10922","title":"Defending the self: The role of oxytocin in responses to psychological threat.","authors":"Feng, Chunliang; Luo, Wenbo; Zhu, Ruida","year":2025,"journal":"Neuroscience and biobehavioral reviews, 179, 106406","doi":"10.1016/j.neubiorev.2025.106406","pmid":"41072564","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review synthesizes evidence across three contexts — intrapersonal, social comparison, and social evaluation — showing that oxytocin consistently modulates processes related to self-protection. Proactive strategies influenced by oxytocin include selective information processing and non-cooperation, while reactive strategies include aggression and cognitive distortion.\n\nThe framework uniquely explains why oxytocin produces seemingly contradictory effects: both prosocial behavior (when cooperation protects self-image) and antisocial behavior (when aggression defends against self-threats) can serve the same underlying function of self-defense. The authors also delineate how oxytocin and the structurally similar neuropeptide vasopressin contribute differently to self-protection mechanisms.","whyItMatters":"The popular narrative of oxytocin as purely a 'bonding' or 'trust' molecule has led to oversimplified therapeutic proposals (e.g., intranasal oxytocin for autism or social anxiety). This more nuanced framework explains why oxytocin interventions sometimes backfire — boosting self-protective aggression or mistrust instead of social warmth. Understanding oxytocin's true function is essential for developing peptide-based therapies that work with, rather than against, its context-dependent nature.","specificNumbers":"","methodology":"This is a theoretical review and framework paper that synthesizes existing research from multiple disciplines — including social neuroscience, evolutionary psychology, and behavioral endocrinology — to propose a unifying model of oxytocin's role in psychological self-defense. It draws on converging findings from intrapersonal, social comparison, and social evaluation contexts.","limitations":"As a theoretical review, this paper does not present new experimental data. The self-protection framework, while integrative, is primarily based on synthesizing existing studies that were not originally designed to test this specific hypothesis. Many of the cited studies used intranasal oxytocin administration, whose brain penetration and dose-response relationships remain debated. The claim that self-protection is 'distinctly human' due to reliance on self-reflection may be difficult to test rigorously. The framework's predictive power — does it generate falsifiable hypotheses better than competing models? — remains to be demonstrated empirically."},{"rthcId":"RPEP-10923","title":"Effect of Hemodialysis Combined With Hemodiafiltration on Cardiac Structure, Function, and Metabolic Indicators in Uremic Patients.","authors":"Feng, Haiyun; Wang, Jindong; Xiang, Yuanhua; Lu, Haiyan; Zhou, Lingjuan","year":2025,"journal":"British journal of hospital medicine (London, England : 2005), 86(5), 1-15","doi":"10.12968/hmed.2024.0928","pmid":"40405851","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10924","title":"Functionally graded scaffold with M2 macrophage-derived LncRNA-Encoded peptide: Mechanistic and therapeutic evaluation for rotator cuff repair.","authors":"Feng, Hao; Zhang, Gonghao; Xiong, Li; Shang, Panpan; Yu, Xiao; Chai, Bin; Han, Lu; Lou, Shuqi; Shafiq, Muhammad; Zhang, Yiying; El-Newehy, Mohamed; Abdulhameed, Meera Moydeen; Yuan, Zhengchao; Mo, Xiumei; Ji, Yunhan","year":2025,"journal":"Bioactive materials, 52, 668-686","doi":"10.1016/j.bioactmat.2025.06.032","pmid":"40613083","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10925","title":"Strategies for neoantigen screening and immunogenicity validation in cancer immunotherapy (Review).","authors":"Feng, Hua; Jin, Yuanting; Wu, Bin","year":2025,"journal":"International journal of oncology, 66(6)","doi":"10.3892/ijo.2025.5749","pmid":"40342048","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10926","title":"Design, Synthesis, and Aphicidal Activity of Novel Insect Neuropeptide Kinin Receptor Antagonists, Targeting the Ser2 Ligand Position.","authors":"Feng, Jia-Wei; Wen, Lu; He, Kang-Li; Luo, Li-Lin; He, Shu-Zhong; Smagghe, Guy; Gui, Shun-Hua; Liu, Tong-Xian","year":2025,"journal":"Journal of agricultural and food chemistry, 73(40), 25505-25514","doi":"10.1021/acs.jafc.5c05232","pmid":"41001716","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10927","title":"Targeting SARS-CoV-2 Receptor Binding Domain and Main Protease with D-Peptides.","authors":"Feng, Laiyi; Liu, Jingjia; Li, Chunmei; Wang, Qian; Lai, Luhua; Zhang, Changsheng","year":2025,"journal":"Journal of chemical information and modeling, 65(20), 11400-11412","doi":"10.1021/acs.jcim.5c01839","pmid":"41030196","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10928","title":"The novel GLP-1 / GIP dual agonist DA3-CH is more effective than liraglutide in the MPTP mouse model of Parkinson's disease.","authors":"Feng, Peng; Liu, ZhaoNa; Lv, DongLiang; Hao, WanDa; Li, DongFang; Xue, GuoFang; Bai, Bo; Hölscher, Christian","year":2025,"journal":"European journal of pharmacology, 1003, 177972","doi":"10.1016/j.ejphar.2025.177972","pmid":"40683437","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10929","title":"An Injectable Antioxidant Parathyroid Hormone Related Supramolecular Peptide Nanofiber Hydrogel for Repairing Osteoporotic Bone Defects.","authors":"Feng, Qinyu; Li, Hanke; Wang, Yi; Wang, Junwu; Zhang, Zheyuan; Hao, Zhuowen; Chen, Renxin; Chen, Tianhong; Shi, Guang; Chen, Jiayao; Zhu, Tonghe; Du, Juan; Hu, Yang; Li, Jingfeng","year":2025,"journal":"ACS applied materials & interfaces, 17(27), 38890-38911","doi":"10.1021/acsami.5c06674","pmid":"40560791","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10930","title":"Myristoylated Cathelicidin-DM Fused With ANG1-7: A Novel Self-Assembling Antimicrobial Peptide for the Treatment and Mechanism of Diabetic Infected Wounds.","authors":"Feng, Rongqin; Wang, Peng; Fan, Li; Lu, He; Yao, Danna; Sun, Panpan; Liu, Zhonghua; Han, Fu; Bai, Xiaozhi; Yang, Xuekang; Han, Juntao","year":2025,"journal":"Journal of diabetes research, 2025, 9601959","doi":"10.1155/jdr/9601959","pmid":"40933728","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10931","title":"Obesity and emerging intervention strategies: mechanistic insights and novel drug targets.","authors":"Feng, Xingrong; Li, Sheyu; Li, Jing; Su, Zhiguang","year":2025,"journal":"Chinese medical journal, 139(2), 182-99","doi":"10.1097/CM9.0000000000003919","pmid":"41396202","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10932","title":"Effectiveness of the Dual GIP/GLP1-Agonist Tirzepatide in 2 Cases of Alström Syndrome, a Rare Obesity Syndrome.","authors":"Ferch, Moritz; Peitsch, Isabel; Kautzky-Willer, Alexandra; Greber-Platzer, Susanne; Stättermayer, Albert Friedrich; Krebs, Michael; Scherer, Thomas","year":2025,"journal":"The Journal of clinical endocrinology and metabolism, 110(12), 3364-3369","doi":"10.1210/clinem/dgaf258","pmid":"40302276","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10933","title":"Effectiveness of Adjuvant Semaglutide Following Bariatric Metabolic Surgery.","authors":"Ferguson, Jorgen; Fisher, Oliver; Talbot, Michael; Rigas, Georgia","year":2025,"journal":"Obesity surgery, 35(3), 694-700","doi":"10.1007/s11695-025-07703-0","pmid":"39982604","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10934","title":"Treatment of Persistent Headache After Normalization of CSF Pressure.","authors":"Fermo, Olga","year":2025,"journal":"Continuum (Minneapolis, Minn.), 31(3), 769-789","doi":null,"pmid":"40459314","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10935","title":"Reducing Periprosthetic Joint Infection in Patients With Obesity: A Systematic Review and Meta-Analysis of the Emerging Role of Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists.","authors":"Fernandes, André; MacAulay, Charlotte; Khater, Abdul R; Matthews, Hannah; Mohrir, Ganesh; Lodge, Christopher","year":2025,"journal":"Cureus, 17(12), e99805","doi":"10.7759/cureus.99805","pmid":"41438726","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10936","title":"Advancing Cardiovascular, Kidney, and Metabolic Medicine: A Narrative Review of Insights and Innovations for the Future.","authors":"Fernando, Kevin; Connolly, Derek; Darcy, Eimear; Evans, Marc; Hinchliffe, William; Holmes, Patrick; Strain, W David","year":2025,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 16(6), 1155-1176","doi":"10.1007/s13300-025-01738-3","pmid":"40272772","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10937","title":"Effects of two different peptides on pentylenetetrazole-induced seizures in larval zebrafish.","authors":"Fernández, Jhonathan Angel Araujo; de Moura, Thatiane Cristina; Vila, Sabela Fernández; Gaytán, Juan Andrés Rubiolo; López-Díaz, Iñaki; Learte-Aymamí, Soraya; Vázquez, M Eugenio; Mayán, Maria D; Sánchez, Laura; Maurer-Morelli, Claudia Vianna","year":2025,"journal":"PloS one, 20(4), e0308581","doi":"10.1371/journal.pone.0308581","pmid":"40279339","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10938","title":"Time-course of mRNA abundance of appetite-regulatory genes in the brain of rainbow trout fed a plant-based diet from the first feeding.","authors":"Fernández-Maestú, Cristina; Martinat, Maud; Calo, Jessica; Velasco, Cristina; Soengas, José L; Roy, Jérôme; Blanco, Ayelén M","year":2025,"journal":"Comparative biochemistry and physiology. Part A, Molecular & integrative physiology, 310, 111939","doi":"10.1016/j.cbpa.2025.111939","pmid":"41061844","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10939","title":"Progress and challenges in obesity pharmacotherapy: semaglutide as a milestone.","authors":"Ferrara, Francesco; Bazzani, Denise; Crivelli, Barbara; Danieli, Elisa; Gazzola, Pietro; Guarnieri, Greta; Handschin, Giulia; Lauria, Claudia; Marchetti, Carlotta; Sbraga, Emanuele; Zero, Carmen; Zovi, Andrea; Langella, Roberto; Parati, Chiara","year":2025,"journal":"Naunyn-Schmiedeberg's archives of pharmacology, 398(11), 15257-15267","doi":"10.1007/s00210-025-04319-0","pmid":"40515833","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10940","title":"Predictive factors for persistent thrombocytopenia after peptide receptor radioligand therapy in enteropancreatic neuroendocrine tumors.","authors":"Ferrara, Romain; Zemmour, Christophe; Reichert, Thibaut; Ouk, Daniel; Niccoli, Patricia; Maniry-Quellier, Jemima; Brenot-Rossi, Isabelle; Charrier, Nathalie; Oziel-Taieb, Sandrine","year":2025,"journal":"Frontiers in endocrinology, 16, 1568243","doi":"10.3389/fendo.2025.1568243","pmid":"40444233","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10941","title":"Early Use of Liraglutide for the Treatment of Acute COVID-19 Infection: An Open-Label Single-Center Phase II Safety Study with Biomarker Profiling.","authors":"Ferreira, Eloara V M; Oliveira, Rudolf K F; Salomao, Reinaldo; Brunialti, Milena K C; Cardoso, Martyella B A; Chen, Chien-Nien; Zhao, Lan; McCabe, Colm","year":2025,"journal":"Infectious disease reports, 17(1)","doi":"10.3390/idr17010005","pmid":"39846709","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Liraglutide (0.6 mg subcutaneously daily for 5 days) was well tolerated by all 13 hospitalized COVID-19 pneumonia patients, with 100% survival at 30 days. In the non-critical group, plasma soluble CD147 levels decreased at day 5, while critical care patients showed an increase in CD147 between days 0-5.\n\nNon-critical patients also demonstrated improved right and left ventricular function on echocardiography, reduced plasma troponin levels (indicating less cardiac damage), increased CD147 expression on T lymphocytes (potentially enhancing immune function), and reduced plasma IL-8 (an inflammatory chemokine). These divergent patterns between mild and severe cases suggest liraglutide's benefits may be most pronounced when given early in disease, before critical illness develops.","whyItMatters":"COVID-19 taught the medical community the importance of having diverse treatment options ready for pandemics. This study demonstrates that GLP-1 drugs — already widely used for diabetes and obesity — could potentially be repurposed for viral infections that cause systemic inflammation and cardiac damage. The CD147 receptor downregulation is particularly interesting because it could reduce viral cell entry, adding an antiviral dimension to GLP-1 drugs' known anti-inflammatory properties.","specificNumbers":"","methodology":"This was an open-label, single-center, phase II safety and tolerability study. Thirteen patients hospitalized with COVID-19 pneumonia received liraglutide 0.6 mg subcutaneously daily for 5 days as add-on therapy to standard of care, initiated within 48 hours of hospital presentation. Biomarker responses (soluble CD147, troponin, IL-8, T lymphocyte CD147 expression) and echocardiographic parameters were measured. Outcomes were compared between patients requiring critical care admission and those who did not.","limitations":"This was a very small (n=13), open-label study with no control group, making it impossible to attribute improvements specifically to liraglutide versus natural disease course. The low liraglutide dose (0.6 mg) was chosen for safety but may not represent the optimal therapeutic dose. The divergent responses between critical and non-critical patients may reflect disease severity rather than differential drug effects. The study was conducted during a specific COVID-19 wave and may not generalize to other variants."},{"rthcId":"RPEP-10942","title":"Headache and GLP-1 receptor agonists: when medications are therapeutic and when they contribute to the symptom.","authors":"Ferreira, Erika Tavares; Garcia, Leidys Marina Pedrozo; Londero, Renata Gomes","year":2025,"journal":"Arquivos de neuro-psiquiatria, 83(10), 1-7","doi":"10.1055/s-0045-1812303","pmid":"41145149","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies a dual relationship between GLP-1 receptor agonists and headache:\n\n**Therapeutic potential:**\n- Weight reduction from GLP-1 RAs can improve IIH-related headaches by decreasing cerebrospinal fluid pressure\n- Obesity increases migraine risk and chronification; weight loss may reduce migraine burden\n- The gut-brain axis connection suggests additional mechanisms through which GLP-1 RAs may influence headache pathways\n\n**Adverse effects:**\n- Headache is a recognized side effect of GLP-1 receptor agonist therapy\n- The mechanism by which GLP-1 RAs cause headache is not fully understood\n\nThe review emphasizes that understanding this dual relationship is important for clinical decision-making in obese patients with headache disorders.","whyItMatters":"With millions of people now taking GLP-1 drugs for weight loss and diabetes, understanding their effects on headache is clinically important. For obese patients who also suffer from chronic migraines or IIH, GLP-1 drugs could address both weight and headache simultaneously. But for patients who develop headaches as a side effect, clinicians need guidance on management. This review helps navigate this nuanced clinical picture.","specificNumbers":"","methodology":"This is a narrative review examining published studies on the relationship between GLP-1 receptor agonists and headache conditions. The authors analyzed evidence for GLP-1 RAs' effects on IIH, migraine, and gut-brain axis-mediated headache mechanisms, as well as data on headache as an adverse effect of these medications.","limitations":"This is a narrative review, not a systematic review or meta-analysis, which may introduce selection bias in the studies discussed. The mechanisms by which GLP-1 RAs both relieve and cause headaches are not fully elucidated. Most evidence for headache improvement comes from weight-loss-mediated effects rather than direct GLP-1 receptor mechanisms in headache pathways. Large-scale clinical trials specifically designed to assess GLP-1 RAs' effects on headache outcomes are lacking."},{"rthcId":"RPEP-10943","title":"Design of a ligand-dependent fluorescent biosensor, based on an engineered lipocalin (anticalin), for the sensitive detection of the Alzheimer β-amyloid peptide.","authors":"Feuerbach, Anna; Skerra, Arne","year":2025,"journal":"Protein engineering, design & selection : PEDS, 38","doi":"10.1093/protein/gzaf012","pmid":"41065719","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The H1GA(D45C)-NBD anticalin conjugate showed a 6-fold increase in fluorescence emission at 546 nm upon binding amyloid-beta peptides, with an ultra-high binding affinity of KD = 1.2 ± 0.8 nM. The sensor maintained its performance in the presence of 5% (w/v) albumin, demonstrating potential for use in complex biological samples. The engineering strategy involved introducing unpaired cysteine residues in the binding loop region and conjugating them with IANBD amide as a solvatochromic fluorophore — a dye whose emission changes based on its chemical environment.","whyItMatters":"Early detection of amyloid-beta peptides is crucial for Alzheimer's diagnosis and monitoring. Current methods are either invasive (cerebrospinal fluid analysis) or expensive (PET brain scans). A simple fluorescent biosensor that detects Aβ peptides in body fluids could enable earlier, cheaper, and more accessible Alzheimer's screening, particularly as new anti-amyloid drugs make early diagnosis increasingly important for treatment decisions.","specificNumbers":"","methodology":"Protein engineering approach where unpaired cysteine residues were introduced at seven positions within the anticalin's binding loops. Five mutants were successfully purified as monomers and conjugated with IANBD amide fluorophore. Ligand-dependent fluorescence was tested with Aβ40 and Aβ42 peptides, and binding affinity was determined. Performance was validated in the presence of 5% albumin to simulate biological fluid conditions.","limitations":"This is a proof-of-concept laboratory study. The biosensor has not been tested with actual patient samples (blood or CSF). The 1.2 nM affinity is excellent, but the concentrations of Aβ peptides in blood are typically in the low picomolar range, so further sensitivity improvements may be needed for blood-based diagnostics. Interference from other proteins or molecules in clinical samples beyond albumin has not been assessed."},{"rthcId":"RPEP-10944","title":"Investigation of the Potency of KALA and REV Cell-Penetrating Peptides for In Vitro/In Vivo Delivery of an HPV Multiepitope DNA Construct.","authors":"Feyzyab, Haleh; Milani, Alireza; Agi, Elnaz; Hashemi, Mehrdad; Bolhassani, Azam","year":2025,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 31(3), e70000","doi":"10.1002/psc.70000","pmid":"39853698","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10945","title":"Study of Intracellular Peptides of the Central Nervous System of Zebrafish (Danio rerio) in a Parkinson's Disease Model.","authors":"Fiametti, Louise O; Franco, Camilla A; Nunes, Leticia O C; de Castro, Leandro M; Santos-Filho, Norival A","year":2025,"journal":"International journal of molecular sciences, 26(5)","doi":"10.3390/ijms26052017","pmid":"40076641","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10946","title":"New Drugs for Resistant Hypertension: Pending Issue?","authors":"Fici, Francesco; Robles, Nicolas Roberto; Tengiz, Istemihan; Grassi, Guido","year":2025,"journal":"Turk Kardiyoloji Dernegi arsivi : Turk Kardiyoloji Derneginin yayin organidir, 53(6), 433 - 440","doi":"10.5543/tkda.2025.74304","pmid":"40679160","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10947","title":"Interplay Between the Mineralocorticoid System, Inflammation, Hypertension, and Kidney Disease.","authors":"Fields, Eviatar; Schiffrin, Ernesto L","year":2025,"journal":"Kidney360, 6(11), 2017-2027","doi":"10.34067/KID.0000000929","pmid":"40694428","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10948","title":"Effect of sleep apnoea interventions on multiple health outcomes: an umbrella review of meta-analyses of randomised controlled trials.","authors":"Figard, Camille; Ben Messaoud, Raoua; Baillieul, Sébastien; Joyeux-Faure, Marie; Destors, Marie; Tamisier, Renaud; Khouri, Charles; Pépin, Jean-Louis","year":2025,"journal":"EClinicalMedicine, 89, 103529","doi":"10.1016/j.eclinm.2025.103529","pmid":"41140453","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In this umbrella review of 230 RCTs involving 36,353 participants, CPAP was the most effective treatment for reducing the apnea-hypopnea index (AHI), with a mean difference of -30.7 events/hour. GLP-1 receptor agonists ranked second: tirzepatide reduced AHI by 21.86 events/hour (SMD -0.84, 95% CI -1.01 to -0.68; moderate-certainty evidence). Mandibular advancement devices came third with an AHI reduction of 11.91 events/hour. For quality of life, physical activity showed the greatest improvement (SMD 1.3), while CPAP showed modest benefits. Only 3% of included evidence was high-certainty, with 68% moderate and 35% low.","whyItMatters":"This is one of the first comprehensive evidence reviews to directly compare GLP-1 receptor agonists against established sleep apnea treatments like CPAP. The finding that tirzepatide ranks second only to CPAP for reducing breathing interruptions is significant — it suggests that peptide-based weight loss medications could become a major treatment option for sleep apnea, potentially offering an alternative for patients who struggle with CPAP adherence.","specificNumbers":"","methodology":"The researchers conducted an umbrella review — a systematic review of meta-analyses — searching PubMed, Embase, Web of Science, and Cochrane from January 2017 to July 2025. They included meta-analyses of randomized controlled trials evaluating sleep apnea interventions. When multiple meta-analyses covered the same treatment-outcome pair, they retained the one with the most RCTs. Quality was assessed using AMSTAR 2, and evidence certainty was graded using the GRADE framework. The protocol was pre-registered in PROSPERO.","limitations":"Only 3% of included evidence was high-certainty. The review was limited to meta-analyses in English, which may exclude relevant non-English literature. Data on long-term safety, adherence, and combination therapies were scarce. The quality of the umbrella review depends on the quality of the underlying meta-analyses, some of which had methodological limitations."},{"rthcId":"RPEP-10949","title":"Analysis of Body Composition and Levels of Antimicrobial Peptides in Patients with Basal Cell Carcinoma: A Preliminary Study.","authors":"Fijałkowska, Marta; Antoszewski, Bogusław; Koziej, Mateusz","year":2025,"journal":"Journal of clinical medicine, 14(2)","doi":"10.3390/jcm14020419","pmid":"39860425","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10950","title":"Exploring the epigenetic modifications of the RONS-TRPA1-CGRP axis in migraine pathophysiology.","authors":"Fila, Michal; Pawlowska, Elzbieta; Krekora, Jan; Mitus-Kenig, Maria; Blasiak, Janusz","year":2025,"journal":"The journal of headache and pain, 26(1), 191","doi":"10.1186/s10194-025-02114-z","pmid":"40890590","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10951","title":"A Journey into the Blue: Current Knowledge and Emerging Insights into Marine-Derived Peptaibols.","authors":"Finamore, Claudia; Festa, Carmen; Cammarota, Mattia; De Marino, Simona; D'Auria, Maria Valeria","year":2025,"journal":"Marine drugs, 23(12)","doi":"10.3390/md23120458","pmid":"41440893","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10952","title":"Piggybacking on nature: exploring the multifaceted world of porcine β-defensins.","authors":"Finatto, Arthur Nery; Meurens, François; de Oliveira Costa, Matheus","year":2025,"journal":"Veterinary research, 56(1), 47","doi":"10.1186/s13567-025-01465-4","pmid":"40033445","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review establishes that porcine β-defensins (pBDs) have dual functionality: direct antimicrobial activity against a range of pathogens and immunomodulatory properties that enhance the broader immune response. Two approaches to enhancing pBD expression have shown promise: dietary supplementation (specific feed components can upregulate defensin production) and gene editing techniques in pigs and porcine cell models.\n\nThe biological roles of pBDs extend beyond simple pathogen killing to include immune cell recruitment, modulation of inflammatory responses, and coordination of adaptive immunity. Clinical trials in swine have validated their efficacy in infection control, supporting their potential as prophylactic and therapeutic alternatives to conventional antibiotics in both veterinary and translational medicine.","whyItMatters":"Antibiotic use in livestock farming is a major driver of antimicrobial resistance, and the agricultural sector consumes more antibiotics globally than human medicine. Enhancing natural defensin production in pigs through diet or genetics could dramatically reduce antibiotic dependency in pork production — one of the largest meat industries worldwide. The translational angle is equally important: pigs are physiologically similar to humans, making porcine defensin research directly relevant to developing antimicrobial peptide therapies for people.","specificNumbers":"","methodology":"This is a comprehensive narrative review (state-of-the-art) synthesizing research on porcine β-defensins from in vitro characterization through animal trials and clinical applications. It covers molecular biology, immunology, nutrition, and gene editing approaches to defensin enhancement.","limitations":"As a review focused on porcine systems, direct human applicability requires further investigation. The gene editing approaches face regulatory and public acceptance challenges. Dietary enhancement of defensin expression may vary with pig genetics, age, and health status. The review does not quantify the degree of antimicrobial activity or compare it to antibiotic efficacy in standardized terms. Long-term effects of enhanced defensin expression (potential autoimmune or inflammatory consequences) are not addressed."},{"rthcId":"RPEP-10953","title":"Effect of the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide on alcohol consumption in alcohol-preferring male vervet monkeys.","authors":"Fink-Jensen, Anders; Wörtwein, Gitta; Klausen, Mette Kruse; Holst, Jens Juul; Hartmann, Bolette; Thomsen, Morgan; Ptito, Maurice; Beierschmitt, Amy; Palmour, Roberta M","year":2025,"journal":"Psychopharmacology, 242(1), 63-70","doi":"10.1007/s00213-024-06637-2","pmid":"38884652","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In a vehicle-controlled study of 20 alcohol-preferring male vervet monkeys, semaglutide (0.05 mg/kg twice weekly subcutaneously) significantly reduced voluntary alcohol intake compared to placebo during a 4-week alcohol access period (4 hours daily, Monday through Friday).\n\nCrucially, there were no signs of emetic events (vomiting or nausea), and water intake was not affected — two important controls suggesting that the reduction in alcohol drinking was not simply due to the monkeys feeling sick or reducing all fluid consumption. The study included a 2-week dose escalation period before alcohol was reintroduced and a 1-week washout period at the end.","whyItMatters":"Alcohol use disorder affects hundreds of millions of people worldwide and current treatments have limited efficacy. The observation that GLP-1 drugs might reduce alcohol consumption has generated enormous clinical interest, but the evidence has been largely from rodent studies and anecdotal human reports. Non-human primates are much closer to humans in brain structure and reward circuitry, so this primate demonstration significantly strengthens the case for clinical trials of semaglutide in alcohol use disorder.","specificNumbers":"","methodology":"This was a vehicle-controlled study in 20 male African green monkeys with demonstrated alcohol preference. After 10 days of baseline alcohol consumption measurement (4 hours daily access), monkeys were randomized to semaglutide (n=10) or vehicle (n=10), balanced for baseline alcohol intake. Semaglutide was escalated to 0.05 mg/kg over 2 weeks (without alcohol access), then maintained for 3 weeks during which alcohol consumption was measured over 20 days. A 1-week washout period followed. Alcohol intake, water intake, and emetic events were monitored.","limitations":"The study used only male monkeys (n=10 per group), so results may not apply to females. The 4-week treatment period is short relative to the chronic nature of alcohol use disorder. The dose (0.05 mg/kg twice weekly) may not directly translate to human clinical dosing. While the monkeys preferred alcohol, they were not alcohol-dependent in the clinical sense — they didn't experience withdrawal or compulsive drinking. The study cannot determine whether semaglutide's effect would persist long-term or whether alcohol consumption would rebound after stopping treatment."},{"rthcId":"RPEP-10954","title":"Neuropeptide Y regulation of L-type Ca 2+ channel activity is altered following chronic myocardial infarction.","authors":"Fiore, Chase M; Agarwal, Shailesh R; Elasoru, Seyi E; Ardell, Jeffrey; Ajijola, Olujimi; Shivkumar, Kalyanam; Harvey, Robert D","year":2025,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2025.11.25.690298","pmid":"41394738","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In healthy pig heart cells, NPY alone stimulated L-type calcium current via Y1/Gq signaling, while NPY in the presence of norepinephrine had an inhibitory effect via Y2/Gi signaling. Following chronic myocardial infarction, the stimulatory Y1-mediated effect was absent in both remote and border zone myocytes. The inhibitory Y2-mediated effect was absent in remote area myocytes but remained intact in border zone cells. This regional heterogeneity in NPY responsiveness could create electrical gradients across the infarcted heart that promote arrhythmias.","whyItMatters":"Sudden cardiac death from arrhythmias is the leading cause of mortality after heart attacks, and elevated NPY is a known marker of this risk. This study reveals for the first time how NPY's effects on calcium channels change in different regions of the damaged heart, providing a mechanistic explanation for post-MI arrhythmias and identifying NPY receptor subtypes as potential therapeutic targets.","specificNumbers":"","methodology":"Researchers used a chronic myocardial infarction pig model and isolated ventricular myocytes from healthy hearts and infarcted hearts (both border zone and remote areas). They measured L-type calcium current using patch-clamp electrophysiology, testing NPY alone and with norepinephrine. Receptor-specific antagonists (BIBO3304 for Y1, BIIE0246 for Y2) confirmed the signaling pathways involved.","limitations":"This is a preprint (bioRxiv) that has not yet undergone peer review. The study used a pig model, which, while closer to human physiology than rodents, may not perfectly replicate human post-MI pathology. The experiments examined isolated myocytes, which removes the complex multicellular interactions present in the intact heart. Only L-type calcium current was studied, while NPY may affect other ion channels relevant to arrhythmias."},{"rthcId":"RPEP-10955","title":"Real-world retrospective study in elderly patients aged 65 years and older with type 2 diabetes mellitus treated with daily oral semaglutide (SEMA-elderly).","authors":"Fiore, Vincenzo; Carbotta, Giovanni; Barraco, Sonia; Falasca, Paolo; Aricò, Concetta Nadia; Barucca, Alessandra","year":2025,"journal":"Diabetes, obesity & metabolism, 27(4), 1805-1814","doi":"10.1111/dom.16174","pmid":"39789997","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10956","title":"Obeticholic Acid and Other Farnesoid-X-Receptor (FXR) Agonists in the Treatment of Liver Disorders.","authors":"Fiorucci, Stefano; Urbani, Ginevra; Distrutti, Eleonora; Biagioli, Michele","year":2025,"journal":"Pharmaceuticals (Basel, Switzerland), 18(9)","doi":"10.3390/ph18091424","pmid":"41011291","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10957","title":"Tirzepatide for metabolic dysfunction-associated steatohepatitis: results from phase II clinical trials and perspectives.","authors":"Fiorucci, Stefano; Urbani, Ginevra","year":2025,"journal":"Expert opinion on investigational drugs, 34(9), 655-663","doi":"10.1080/13543784.2025.2546812","pmid":"40782123","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10958","title":"The HER2 target for designing novel multi-peptide vaccine against breast cancer using immunoinformatics and molecular dynamic simulation.","authors":"Firuzpour, Faezeh; Barancheshmeh, Maryam; Ziarani, Fariba Fallah; Karami, Leila; Aram, Cena","year":2025,"journal":"Biochemistry and biophysics reports, 43, 102135","doi":"10.1016/j.bbrep.2025.102135","pmid":"40688509","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10959","title":"Application of nutrition interventions with GLP-1 based therapies: A narrative review of the challenges and solutions.","authors":"Fitch, Angela; Gigliotti, Linda; Bays, Harold Edward","year":2025,"journal":"Obesity pillars, 16, 100205","doi":"10.1016/j.obpill.2025.100205","pmid":"41018564","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10960","title":"Investigation of Angiotensin I-Converting Enzyme Inhibitory Peptides Derived from Germinated Lamtoro Gung Using In Vitro and In Silico Approaches.","authors":"Fitriani, Aprilia; Indrati, Retno; Marsono, Yustinus; Supriyadi, Supriyadi","year":2025,"journal":"Preventive nutrition and food science, 30(6), 607-617","doi":"10.3746/pnf.2025.30.6.607","pmid":"41492427","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10961","title":"Differences in pharmacological migraine treatment across different levels of clinical headache care - a cross-sectional study.","authors":"Fitzek, Mira Pauline; Overeem, Lucas Hendrik; Ulrich, Marlene; Hong, Ja Bin; Hoehne, Carolin Luisa; Lange, Kristin Sophie; Salim, Yones; Reuter, Uwe; Raffaelli, Bianca","year":2025,"journal":"The journal of headache and pain, 26(1), 78","doi":"10.1186/s10194-025-02027-x","pmid":"40229741","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10962","title":"Cardiometabolic Therapies Shape Non-Coding RNA Landscapes in Cardiovascular Fibrosis.","authors":"Floris, Erica; Nutile, Francesco; Cozzolino, Claudia; Pontecorvi, Virginia; Bordin, Antonella; De Falco, Elena; Picchio, Vittorio; Chimenti, Isotta; Pagano, Francesca","year":2025,"journal":"Metabolites, 15(10)","doi":"10.3390/metabo15100664","pmid":"41149642","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10963","title":"Leveraging mRNA technology for antigen based immuno-oncology therapies.","authors":"Floudas, Charalampos S; Sarkizova, Siranush; Ceccarelli, Michele; Zheng, Wei","year":2025,"journal":"Journal for immunotherapy of cancer, 13(1)","doi":"10.1136/jitc-2024-010569","pmid":"39848687","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review establishes mRNA as an ideal platform for personalized neoantigen cancer immunotherapy due to its versatility and rapid development potential. Key neoantigen selection criteria include: peptide presentation on HLA molecules, HLA-peptide binding affinity, and T cell receptor recognition — all assessed through advanced computational algorithms using next-generation sequencing data. The review covers both shared antigens (common across patients) and individual neoantigens (unique to each patient's tumor), discussing the computational workflows, design considerations for immunogenicity and stability, and clinical trial evidence supporting this approach.","whyItMatters":"Personalized mRNA cancer vaccines represent one of the most promising new approaches to cancer treatment. Understanding how to select the right peptide targets is the critical bottleneck. This review synthesizes the computational and biological principles that guide neoantigen selection, providing a roadmap for the field. With major clinical trials underway (Moderna/Merck's mRNA-4157 for melanoma, BioNTech's individualized vaccines), the stakes are enormous.","specificNumbers":"Covers: shared + individual neoantigens · HLA-peptide-TCR complex formation · Next-gen sequencing workflows · Multiple clinical trials reviewed","methodology":"Comprehensive review of the development and clinical application of mRNA-based cancer vaccines, covering computational workflows for neoantigen identification and prioritization, antigen target strategies (tumor-associated vs. tumor-specific), mRNA design considerations, and clinical trial data. Focuses on therapeutic (not preventive) cancer vaccines.","limitations":"As a review, no new experimental data is presented. The field is rapidly evolving, so some discussed methods may already be superseded. The review acknowledges that neoantigen prediction remains imperfect — many predicted neoantigens fail to elicit immune responses in practice. Clinical outcomes from mRNA cancer vaccine trials are still early and often combined with other immunotherapies, making it difficult to isolate the vaccine's contribution."},{"rthcId":"RPEP-10964","title":"The clinical outcome of patients starting monoclonal antibodies anti-CGRP with concomitant migraine preventive treatments.","authors":"Fofi, Luisa; Altamura, Claudia; Marcosano, Marilena; Brunelli, Nicoletta; Iannone, Luigi Francesco; Doretti, Alberto; Viticchi, Giovanna; De Cesaris, Francesco; Alesina, Alessandro; Silvestrini, Mauro; Peresson, Marco; Vernieri, Fabrizio","year":2025,"journal":"Cephalalgia : an international journal of headache, 45(10), 3331024251378776","doi":"10.1177/03331024251378776","pmid":"41105547","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10965","title":"Bed Nucleus of the Stria Terminalis PACAP Signaling in the Dorsal Medial Habenula Mediates Depression-Related Behavioral Responses After Chronic Stress.","authors":"Fontaine, Nicholas R; Lepeak, Lauren; Aktar, Mahafuza; Mahler, Aimee; Black, William; Hannibal, Jens; Vizzard, Margaret A; May, Victor; Hammack, Sayamwong E","year":2025,"journal":"Biological psychiatry","doi":"10.1016/j.biopsych.2025.11.013","pmid":"41297784","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10966","title":"Mass spectrometry peptidomics data from infected and uninfected porcine wounds.","authors":"Forsberg, Fredrik; Kjellström, Sven; Petrlova, Jitka; Puthia, Manoj; Schmidtchen, Artur; Malmström, Johan; Hartman, Erik","year":2025,"journal":"Scientific data, 12(1), 1533","doi":"10.1038/s41597-025-05842-8","pmid":"40897740","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10967","title":"CGRP+ fibers sprout within gastrocnemius muscle following complete spinal cord injury in rodents.","authors":"Forston, Morgan J; Ohkubo, Alan; Forston, Michael D; DeHoff, Mary Ellen; Shum-Siu, Alice; Magnuson, David S K","year":2025,"journal":"Experimental neurology, 393, 115400","doi":"10.1016/j.expneurol.2025.115400","pmid":"40721106","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10968","title":"Proteomic and peptidomic profiling of spirulina-fortified probiotic powder formulations during in vitro digestion.","authors":"Fortuin, Jennyfer; Leclercq, Céline C; Iken, Marcus; Villas-Boas, Silas G; Soukoulis, Christos","year":2025,"journal":"International journal of biological macromolecules, 302, 140432","doi":"10.1016/j.ijbiomac.2025.140432","pmid":"39884605","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10969","title":"The GLP-1R Agonist Semaglutide Reduces Motivated Running and Alters Dopamine Dynamics in the Nucleus Accumbens.","authors":"Foscue, Ethan P; Trinko, Joseph R; Jiménez, Jaysen Lara; Kong, Edward; Thompson, Summer L; Stankewich, Kiera; Corstens, Anouk M; Serlie, Mireille J; Taylor, Jane R; DiLeone, Ralph J","year":2025,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2025.10.08.681212","pmid":"41279988","tags":["semaglutide","GLP-1-agonists","dopamine","reward-system"],"studyType":"animal","evidenceStrength":"preliminary","keyFinding":"Semaglutide suppressed voluntary wheel running in both lean and obese mice — and this wasn't just because the mice were eating less. In a progressive ratio task (where mice had to work harder and harder to access the running wheel), semaglutide-treated mice showed reduced motivation to exert effort for exercise.\n\nReal-time dopamine measurements using fiber photometry revealed that semaglutide amplified dopamine dynamics in the nucleus accumbens (the brain's reward center) at the start and end of running bouts. This suggests semaglutide doesn't just suppress appetite — it alters the brain's reward circuitry in ways that reduce motivation for non-food activities like exercise.","whyItMatters":"One of the biggest concerns about GLP-1 weight loss drugs is whether they cause muscle loss, and exercise is the primary tool patients use to counteract this. If semaglutide directly reduces exercise motivation through dopamine pathways — independent of its appetite effects — that's a clinically important finding. It could help explain why some patients on these drugs report reduced drive to exercise and has implications for how weight loss is maintained.","specificNumbers":"","methodology":"Animal study using lean and diet-induced obese mice. Voluntary wheel running was measured to assess activity levels. Motivation was tested using a progressive ratio task where mice pressed a lever with increasing effort requirements to access a running wheel. Real-time dopamine dynamics in the nucleus accumbens were measured using fiber photometry during running bouts.","limitations":"Mouse study — dopamine dynamics and exercise motivation may not directly translate to human behavior. The study used a preprint server (bioRxiv), meaning it hasn't completed peer review. Wheel running is an innate rodent behavior that may not perfectly model human exercise motivation. The doses and pharmacokinetics of semaglutide in mice differ from human use."},{"rthcId":"RPEP-10970","title":"Constructing chimeric mouse islets to study alpha- and delta-cell influence on beta-cell feature.","authors":"Fouque, Alexis; Oshima, Masaya; Mode, Nina; Ducellier, Romain; Thibaut, Delphine; Gbahou, Florence; Rachdi, Latif; Cabrera, Over; Scharfmann, Raphaël","year":2025,"journal":"Molecular metabolism, 101, 102245","doi":"10.1016/j.molmet.2025.102245","pmid":"40902847","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10971","title":"Liraglutide for Children 6 to <12 Years of Age with Obesity - A Randomized Trial.","authors":"Fox, Claudia K; Barrientos-Pérez, Margarita; Bomberg, Eric M; Dcruz, John; Gies, Inge; Harder-Lauridsen, Nina M; Jalaludin, Muhammad Yazid; Sahu, Kushal; Weimers, Petra; Zueger, Thomas; Arslanian, Silva","year":2025,"journal":"The New England journal of medicine, 392(6), 555-565","doi":"10.1056/NEJMoa2407379","pmid":"39258838","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"At week 56, liraglutide 3.0mg daily produced significantly better outcomes than placebo:\n- BMI change: -5.8% vs +1.6% (difference: -7.4 percentage points, P<0.001)\n- Body weight change: +1.6% vs +10.0% (difference: -8.4 percentage points, P=0.001)\n- ≥5% BMI reduction: 46% vs 9% (adjusted OR 6.3, P=0.02)\n\nNote that children in both groups gained weight (they're growing), but liraglutide children gained dramatically less. Adverse events were similar overall (89% vs 88%), but GI events were higher with liraglutide (80% vs 54%). Serious adverse events: 12% liraglutide vs 8% placebo.","whyItMatters":"Childhood obesity is a growing epidemic with lifelong health consequences, yet no medications are approved for children under 12. This NEJM trial provides the first randomized evidence that a GLP-1 peptide drug is effective in this young age group, potentially opening the door to earlier pharmacological intervention before metabolic complications become entrenched.","specificNumbers":"","methodology":"Phase 3a randomized, double-blind, placebo-controlled trial (SCALE Kids). 82 children aged 6 to <12 years with obesity were randomized 2:1 to liraglutide 3.0mg (or maximum tolerated dose) or placebo, both with lifestyle interventions. 56-week treatment period followed by 26-week follow-up. Primary endpoint: percentage change in BMI. (NCT04775082, funded by Novo Nordisk.)","limitations":"Small sample size (n=82) limits the ability to detect rare adverse events. Short treatment duration (56 weeks) — long-term safety in growing children is unknown. High rate of GI adverse events (80%) raises tolerability concerns. The study was funded by Novo Nordisk (liraglutide's manufacturer). Children were still growing, making BMI change interpretation complex. The 26-week follow-up period will be important for understanding weight trajectory after stopping treatment."},{"rthcId":"RPEP-10972","title":"Integrated Genetic and Protein Mechanisms Underlying Glucagon-like Peptide-1 Receptor Agonists in Treating Diabetes Mellitus and Weight Loss.","authors":"Francis, Lucas; Butler, Merlin G","year":2025,"journal":"Current issues in molecular biology, 47(12)","doi":"10.3390/cimb47121007","pmid":"41614771","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10973","title":"Tirzepatide for adults living with obesity.","authors":"Franco, Juan Va; Guo, Yang; Varela, Lucia B; Aqra, Zakariya; Alhalahla, Murad; Medina Rodriguez, Mauricio; Salvador Oscco, Edison Leonardo; Patiño Araujo, Bernarda; Banda, Susan; Escobar Liquitay, Camila Micaela; Bracchiglione, Javier; Meza, Nicolás; Madrid, Eva","year":2025,"journal":"The Cochrane database of systematic reviews, 10(10), CD016018","doi":"10.1002/14651858.CD016018","pmid":"41161687","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10974","title":"Preanalytical stability of plasma calcitonin gene-related peptide: clinical and research implications.","authors":"Frank, Florian; Eller, Michael Thomas; Maier, Sarah; Janisch, Laura; Labrecque, Samuel; Kaltseis, Katharina; Messlinger, Karl; Reindl, Markus; Broessner, Gregor","year":2025,"journal":"The journal of headache and pain, 26(1), 261","doi":"10.1186/s10194-025-02205-x","pmid":"41249915","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10975","title":"Short-term prevention of perimenstrual migraine with rimegepant.","authors":"Frank, Florian; Schiefecker, Alois; Kaltseis, Katharina; Eller, Michael; Broessner, Gregor","year":2025,"journal":"The journal of headache and pain, 26(1), 253","doi":"10.1186/s10194-025-02185-y","pmid":"41225335","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Rimegepant 75 mg taken every other day during the perimenstrual window prevented anticipated migraine attacks in 17 out of 20 treatment cycles (85%), with no adverse events reported. However, the picture was more nuanced: only one patient (20%) achieved a sustained reduction in total monthly migraine days. Three patients (60%) experienced a 'temporal displacement' phenomenon, where migraine attacks that were prevented during the perimenstrual window reappeared 3–7 days after menstruation ended.\n\nAll five patients reported high satisfaction with perimenstrual symptom control despite the displacement effect, suggesting that even shifting migraines away from the most symptomatic period provided meaningful clinical benefit.","whyItMatters":"Menstrual migraines are among the most debilitating and treatment-resistant migraine subtypes. Traditional short-term prevention with NSAIDs or triptans often fails or is contraindicated. Rimegepant, which targets the CGRP peptide pathway central to migraine pathophysiology, offers a targeted approach. The 'temporal displacement' finding is particularly important — it suggests that CGRP blockade alone may not address the underlying hormonal trigger, pointing to complex interactions between estrogen withdrawal and peptide signaling in migraine.","specificNumbers":"","methodology":"This hypothesis-generating case series enrolled five women aged 22–42 with episodic migraine and regular menstrual cycles. Each received rimegepant 75 mg orally disintegrating tablet every other day, starting two days before menstruation and continuing until two days post-menstruation. Patients maintained daily headache diaries recording migraine days, severity, and treatment use. Outcomes included perimenstrual migraine day reduction, overall monthly migraine frequency, tolerability, and adverse events. Follow-up was conducted after 3–4 treatment cycles.","limitations":"This is a very small case series of only five patients with no control group, blinding, or randomization. The 85% prevention rate may overestimate effectiveness due to the small sample and potential placebo effect. The temporal displacement observation, while intriguing, could also reflect natural migraine variability. The every-other-day dosing schedule was not compared to daily dosing or other regimens. These preliminary findings require confirmation in randomized controlled trials."},{"rthcId":"RPEP-10976","title":"Intracellular Delivery of Native Proteins by BioReversible Arginine Modification (BioRAM) on Amino Groups.","authors":"Franke, Jonathan; Arafiles, Jan Vincent V; Leis, Christian; Hackenberger, Christian P R","year":2025,"journal":"Angewandte Chemie (International ed. in English), 64(34), e202506802","doi":"10.1002/anie.202506802","pmid":"40452583","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10977","title":"Impact of GLP-1 receptor agonists on gastrointestinal function and symptoms.","authors":"Frazier, Rosita D; Hasler, William L","year":2025,"journal":"Expert review of gastroenterology & hepatology, 19(11), 1181-1195","doi":"10.1080/17474124.2025.2579117","pmid":"41138239","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 receptor agonists affect gastrointestinal function primarily by slowing gastric emptying and gut transit, which directly contributes to their most common adverse events including nausea, vomiting, and gastroparesis-like symptoms.\n\nA key safety concern highlighted is gastric food retention caused by GLP-1RAs, which increases the risk of pulmonary aspiration during procedures requiring anesthesia. This has prompted changes to pre-anesthesia guidelines for patients taking these medications.\n\nThe review also identifies associations between GLP-1RA use and extraintestinal complications including biliary tract disease and pancreatitis. Importantly, current management recommendations — including dosing adjustments, dietary modifications, and pharmacotherapy for GI symptoms — are described as empiric rather than evidence-based.","whyItMatters":"With millions of people now taking GLP-1 receptor agonists for weight loss and diabetes, understanding the gastrointestinal consequences is critical for both patients and clinicians. The finding that current management strategies lack evidence-based support highlights a significant gap in care, and the aspiration risk during anesthesia has direct implications for surgical safety protocols.","specificNumbers":"","methodology":"The authors conducted a comprehensive literature search of PubMed and EMBASE databases covering publications from July 1987 through August 2025. They synthesized findings on GLP-1 physiology, GLP-1RA effects on GI transit and motility, associated symptoms, and management approaches into a narrative review.","limitations":"This is a narrative review, not a systematic review or meta-analysis, so the literature search may not be exhaustive. The review does not quantify the incidence rates of specific GI adverse events across different GLP-1RAs. Management recommendations are acknowledged by the authors themselves as lacking evidence-based support, meaning the guidance offered is largely expert opinion."},{"rthcId":"RPEP-10978","title":"Pharmacotherapy for Obesity: Recent Updates.","authors":"Fredrick, Thomas Ward; Camilleri, Michael; Acosta, Andres","year":2025,"journal":"Clinical pharmacology : advances and applications, 17, 305-327","doi":"10.2147/CPAA.S497904","pmid":"40995421","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10979","title":"Efficacy of the GLP-1 receptor agonist, semaglutide, in abstinence from illicit and nonprescribed opioids in an outpatient population with treatment-refractory OUD: A randomized, double-blind, placebo-controlled clinical trial protocol.","authors":"Freet, Christopher S; Shuler, Kirsten; Kawasaki, Sarah; Weintraub, Eric; Greenblatt, Aaron; Kladney, Mat; Nunes, Edward; Foster, Katrina L; Kong, Lan; Raja-Khan, Nazia; Cleveland, H Harrington; Grigson, Patricia S; Bunce, Scott C; Brick, Timothy R; Nyland, Jennifer E","year":2025,"journal":"Research square","doi":"10.21203/rs.3.rs-6666196/v1","pmid":"40502777","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"This is a clinical trial protocol — no results are reported yet. The study design is:\n\n- Phase II randomized, double-blind, placebo-controlled trial\n- 200 participants with treatment-refractory OUD (100 on buprenorphine, 100 on methadone)\n- Intervention: semaglutide (GLP-1 RA) vs. placebo added to existing MOUD\n- Primary outcomes: probability of opioid abstinence, craving measures, days of drug use\n- Assessment: urine toxicology screens and self-report across 19 weeks (12 treatment weeks + washout + follow-up)\n- Registered: ClinicalTrials.gov NCT06548490","whyItMatters":"The opioid crisis has killed hundreds of thousands of people, and existing treatments for opioid addiction — while helpful — have high relapse rates, especially in treatment-resistant cases. If semaglutide can reduce opioid cravings through GLP-1 receptor pathways in the brain's reward system, it would represent an entirely new class of addiction medication — one that doesn't act on opioid receptors and could complement existing treatments.","specificNumbers":"","methodology":"Randomized, double-blind, placebo-controlled clinical trial. Participants are 200 adults enrolled in outpatient medication for opioid use disorder (MOUD) programs — split evenly between buprenorphine and methadone patients. After screening (week 1), participants receive 12 weeks of semaglutide or placebo (weeks 2-13), followed by a washout visit (week 14) and final follow-up (week 19). Outcomes assessed via urine drug screens and self-report measures.","limitations":"This is a protocol paper — no results are available. The study is Phase II with 200 participants, which may not be large enough to detect modest effect sizes. The 12-week treatment duration is relatively short for evaluating sustained abstinence. The preprint (Research Square) has not been peer-reviewed. Generalizability may be limited to outpatient MOUD populations."},{"rthcId":"RPEP-10980","title":"Efficacy of Semaglutide as Adjuvant Treatment for Sleeve Gastrectomy: A Proof-of-Concept Study in Mice.","authors":"Frey, Samuel; Louis-Gaubert, Clément; Thouzeau, Amélie; Cossé, Lola; Lorant, Victoria; Prieur, Xavier; Flet, Laurent; Cariou, Bertrand; Blanchard, Claire Louis; Le May, Cédric","year":2025,"journal":"Obesity (Silver Spring, Md.), 33(11), 2061-2066","doi":"10.1002/oby.70003","pmid":"40898674","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10981","title":"What is the 'real-world' experience with fixed-ratio combination therapy (insulin + GLP-1 receptor agonist) in routine clinical practice? Take-home messages for clinicians regarding key outcomes.","authors":"Frias, Juan Pablo","year":2025,"journal":"Diabetes, obesity & metabolism, 27 Suppl 7(Suppl 7), 26-41","doi":"10.1111/dom.16593","pmid":"40637050","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10982","title":"ProSAAS neuropeptides and receptors GPR171 and GPR83: Potential therapeutic applications for pain, anxiety, and body weight regulation.","authors":"Fricker, Lloyd D; Fakira, Amanda K; Bobeck, Erin N; Raddatz, Megan; Kim, Kelly; DeSchepper, Kayla D; Morgan, Daniel J","year":2025,"journal":"The Journal of pharmacology and experimental therapeutics, 392(6), 103599","doi":"10.1016/j.jpet.2025.103599","pmid":"40450835","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10983","title":"Abdominoplasty Outcomes after GLP-1 Agonist-Induced versus Post-Bariatric Massive Weight Loss: A Retrospective Comparative Case Series.","authors":"Friedman, Or; Tal, Daniel","year":2025,"journal":"Plastic and reconstructive surgery","doi":"10.1097/PRS.0000000000012523","pmid":"41118524","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 patients had significantly higher albumin (4.0 vs 3.6 g/dL, p=0.021) and prealbumin levels (23.2 vs 18.9 mg/dL, p=0.003) than bariatric surgery patients, indicating superior nutritional status. The overall complication rate trended lower in GLP-1 patients (20% vs 40%, OR 0.38), though this did not reach statistical significance (p=0.301) in this 40-patient study.\n\nAfter multivariable adjustment controlling for weight loss magnitude, duration, albumin, and pannus weight, the direction of effect continued to favor GLP-1 patients (adjusted OR 0.72, p=0.830). GLP-1 patients had less total weight loss (29.9 vs 47.2 kg, p<0.001), which may partly explain the better outcomes.","whyItMatters":"The GLP-1 drug revolution is creating an entirely new population of massive weight loss patients seeking body contouring surgery. Unlike post-bariatric patients, these individuals haven't had surgical alteration of their digestive system and may retain better nutritional status. Understanding how this difference affects surgical outcomes is critical for the rapidly growing field of post-GLP-1 body contouring.","specificNumbers":"","methodology":"This was a retrospective comparative case series conducted from January 2022 to November 2024. Twenty patients who achieved massive weight loss (≥20 kg) through GLP-1 therapy were matched 1:1 with post-bariatric surgery controls by sex, age (±5 years), and postoperative BMI (±3 kg/m²). All patients underwent abdominoplasty. The primary outcome was any complication within 90 days. Multivariable analysis was used to assess the independent effect of weight loss method.","limitations":"The sample size was very small (20 per group), making the study underpowered to detect statistically significant differences in complication rates. The retrospective design introduces potential selection bias. GLP-1 patients lost significantly less weight (29.9 vs 47.2 kg), which complicates direct comparison. The study period is relatively short, and long-term outcomes including weight regain and revision rates were not assessed. The study also did not specify which GLP-1 agents were used or their dosing."},{"rthcId":"RPEP-10984","title":"Breast reduction outcomes in massive weight loss: A comparative analysis of GLP-1 receptor agonist users, post-bariatric surgery patients, and controls.","authors":"Friedman, Or; Tal, Daniel","year":2025,"journal":"Journal of plastic, reconstructive & aesthetic surgery : JPRAS, 110, 219-228","doi":"10.1016/j.bjps.2025.09.023","pmid":"41066871","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10985","title":"Effects of preoperative glucagon-like peptide-1 receptor agonist therapy on weight loss following bariatric surgery.","authors":"Friesch, Mason; Fernando, Mitchel; Sheedy, Emma; Helenowski, Irena; Wool, Laura; Edwards, Monica; Brown, Kevin; Lau, James; Cohn, Tyler","year":2025,"journal":"Surgical endoscopy, 39(7), 4545-4550","doi":"10.1007/s00464-025-11838-7","pmid":"40490579","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10986","title":"Effect of iGlarLixi on continuous glucose monitoring-measured time in range in insulin-naive adults with suboptimally controlled type 2 diabetes.","authors":"Frías, Juan P; Ratzki-Leewing, Alexandria; Dex, Terry; Meneghini, Luigi; Rodrigues, Amélie; Shah, Viral N","year":2025,"journal":"Diabetes, obesity & metabolism, 27(4), 2173-2182","doi":"10.1111/dom.16214","pmid":"39905643","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10987","title":"Glucagon-Like Peptide-1 Receptor Agonists: A Novel Indication for Substance Use Disorders?","authors":"Ftiha, Farage; Ftiha, Joey; Parikh, Manish A; Frishman, William H; Peterson, Stephen J","year":2025,"journal":"Cardiology in review","doi":"10.1097/CRD.0000000000001145","pmid":"41398454","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10988","title":"Host-defence caerin 1.1 and 1.9 peptides suppress B16 melanoma growth by inducing apoptosis and disrupting lipid metabolism.","authors":"Fu, Jiawei; Song, Xinyi; Mo, Rongmi; Sebold, Bernardo Cavallazzi; Luo, Yuandong; Li, Junjie; Fu, Quanlan; Li, Hejie; Liu, Xiaosong; Wang, Tianfang; Ni, Guoying","year":2025,"journal":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 189, 118242","doi":"10.1016/j.biopha.2025.118242","pmid":"40516331","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10989","title":"Effects of Combination Treatment with Leptin and Liraglutide on Glucose Metabolism in Insulin-Dependent Diabetic Mice.","authors":"Fu, Linlin; Sugiyama, Mariko; Kamal, Shahriar; Ide, Tsubasa; Takeda, Tadashi; Kuno, Mitsuhiro; Takagi, Hiroshi; Koike, Teruhiko; Arima, Hiroshi; Banno, Ryoichi","year":2025,"journal":"International journal of molecular sciences, 26(10)","doi":"10.3390/ijms26104595","pmid":"40429740","tags":[],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Combining leptin and liraglutide (a GLP-1 receptor agonist) normalized blood glucose levels in mice with insulin-dependent diabetes — achieving glucose control comparable to healthy mice, without any insulin treatment.\n\nEach peptide worked on its own: both leptin monotherapy and liraglutide monotherapy significantly improved blood glucose levels and glucose tolerance compared to untreated diabetic mice. But the combination (LEP+LIRA) outperformed either alone, restoring glucose metabolism to levels indistinguishable from healthy control mice.","whyItMatters":"Type 1 diabetes currently requires lifelong insulin injections. If a combination of leptin and a GLP-1 agonist could partially or fully replace insulin in some patients, it could fundamentally change treatment options. This animal study provides early proof-of-concept that two non-insulin peptide hormones working together can achieve what neither does alone — complete glucose normalization in insulin-dependent diabetes.","specificNumbers":"Leptin: 20 μg/day via osmotic pump · Liraglutide: 1000 μg/kg/day subcutaneously · LEP+LIRA glucose levels comparable to healthy controls · STZ-induced IDDM in 12-week-old C57BL/6J mice","methodology":"Researchers induced insulin-dependent diabetes in male mice using high-dose streptozotocin (which destroys insulin-producing beta cells). Diabetic mice were divided into four groups: leptin alone, liraglutide alone, leptin plus liraglutide, and untreated. A fifth group of healthy mice served as controls. Blood glucose was measured and glucose tolerance tests were performed to compare all five groups.","limitations":"This is a mouse study using chemically induced diabetes, which doesn't perfectly replicate human type 1 diabetes (an autoimmune disease). The abstract doesn't report specific glucose numbers, sample sizes per group, or statistical comparisons between the combination and monotherapy groups. Streptozotocin-induced diabetes destroys beta cells but lacks the autoimmune component. Long-term safety and durability of the effect were not assessed."},{"rthcId":"RPEP-10990","title":"Hemocyanin-derived antimicrobial peptide PvL1 defense against AHPND infection by regulating the hepatopancreatic microbiota of Penaeus vannamei.","authors":"Fu, Maoshuai; Liao, Minrui; Qin, Yingmei; He, Lixuan; Zheng, Zhihong; Zhao, Yongzhen; Liu, Qingyun; Zhang, Yueling; Zhao, Xianliang","year":2025,"journal":"Fish & shellfish immunology, 161, 110267","doi":"10.1016/j.fsi.2025.110267","pmid":"40064216","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10991","title":"Cost-effectiveness analysis of four glucagon-like peptide-1 or glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonists for the treatment of adult patients with overweight and obesity in China.","authors":"Fu, Wu; Lin, Jingwen; You, Caicong; Zhang, Jiahao; Lei, Jianying; Zheng, Liushi; Zheng, Bin; Liu, Maobai; Liu, Libin; Li, Na","year":2025,"journal":"Diabetes, obesity & metabolism, 27(9), 5280-5290","doi":"10.1111/dom.16581","pmid":"40613325","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10992","title":"Janus-structured Reg/PVA/PAN@TiO2 nanofiber dressing containing RegIIIγ recombinant antimicrobial peptides for promoting wound healing.","authors":"Fu, Xuewei; Chen, Jianrong; Jian, Xuewen; Wang, Junkai; Liao, Minjian; Xiong, Pin; Wu, Xiaochun; Liu, Yuqiao; Dong, Xianming; Zhou, Wuyi; Zhao, Hui","year":2025,"journal":"RSC advances, 15(52), 44637-44648","doi":"10.1039/d5ra05169j","pmid":"41255872","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10993","title":"Design, Synthesis, and Biological Evaluation of Arginine N-Glycosylation Stapled Peptides with Potent Antitumor Activity In Vivo.","authors":"Fu, Yinxue; Dou, Chunhui; Gao, Xiaoyang; Ji, Shanping; Zhao, Xuemei; Xue, Jingwen; Yang, Hao; Song, Nannan; Zhang, Chunyu; Wang, Changlong; Li, Yulei","year":2025,"journal":"Journal of medicinal chemistry, 68(19), 20435-20448","doi":"10.1021/acs.jmedchem.5c01550","pmid":"40977558","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10994","title":"A \"Mesoporous Oxygen Chamber\" Scaffold with Antibacterial and Early Immunomodulatory Effect for Promoting Bone Regeneration.","authors":"Fu, You; Lin, Dan; Lu, Zhicen; Wang, Jian; Zhao, Jing; Zhang, Zhiyuan; Fang, Bing; Yang, Xiao","year":2025,"journal":"Advanced science (Weinheim, Baden-Wurttemberg, Germany), 12(41), e06737","doi":"10.1002/advs.202506737","pmid":"40956286","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10995","title":"Aged garlic extract enhances the production of β‑defensin 4 via activation of the Wnt/β‑catenin pathway in mouse gingiva.","authors":"Fujii, Daiki; Nango, Hiroshi; Ohtani, Masahiro","year":2025,"journal":"Experimental and therapeutic medicine, 29(2), 41","doi":"10.3892/etm.2024.12791","pmid":"39781190","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10996","title":"Comparative analysis of plasma BNP and NT-proBNP levels, and NT-proBNP/BNP ratio in patients with chronic kidney disease.","authors":"Fujii, Hideki; Goto, Shunsuke","year":2025,"journal":"Hypertension research : official journal of the Japanese Society of Hypertension, 48(9), 2303-2314","doi":"10.1038/s41440-025-02272-2","pmid":"40595360","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10997","title":"Prediction of Japan Score and Society of Thoracic Surgeons Risk Scores for Patients Undergoing Cardiovascular Surgery by Serum Growth Differentiation Factor-15 and Endothelin-1 Levels.","authors":"Fukuda, Taira; Kato, Takashi; Kanazawa, Yuta; Hirai, Rina; Ishizaka, Hayato; Tan, Hideaki; Shibasaki, Ikuko; Fukuda, Hirotsugu; Toyoda, Shigeru; Nakajima, Toshiaki","year":2025,"journal":"Cureus, 17(4), e82508","doi":"10.7759/cureus.82508","pmid":"40385809","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10998","title":"Development of blood-brain barrier-penetrating antibodies for neutralizing tick-borne encephalitis virus in the brain.","authors":"Fukuta, Mizuki; Fukano, Sayo; Maekawa, Naoya; Kobayashi, Shintaro; Okamoto, Shunsuke; Hirano, Minato; Nio-Kobayashi, Junko; Kariwa, Hiroaki; Kawakami, Shigeru; Konnai, Satoru; Yoshii, Kentaro","year":2025,"journal":"mSphere, 10(7), e0018425","doi":"10.1128/msphere.00184-25","pmid":"40622136","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-10999","title":"Three-Dimensional Analysis of the Effect of Osteosarcoma on Sensory Nerves Innervating the Femur in a Murine Model of Osteosarcoma-Induced Bone Pain.","authors":"Fuller-Jackson, John-Paul; Hopkins, Chelsea; Thai, Jenny; Lassen, Mie Brandt; Heegaard, Anne-Marie; Ivanusic, Jason","year":2025,"journal":"Cancers, 17(21)","doi":"10.3390/cancers17213533","pmid":"41228327","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11000","title":"Tirzepatide-induced weight loss and obstructive sleep apnea improvement in an adult with type 2 diabetes: A case report.","authors":"Funamizu, Noriko; Funamizu, Naotake; Hirose, Tsunemichi","year":2025,"journal":"Medicine, 104(43), e45445","doi":"10.1097/MD.0000000000045445","pmid":"41137356","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11001","title":"Splenectomy prevents brain orexin, ghrelin, or oxytocin but not GLP-1-induced improvement of intestinal barrier function in rats.","authors":"Funayama, Takuya; Nozu, Tsukasa; Ishioh, Masatomo; Igarashi, Sho; Tanaka, Hiroki; Sumi, Chihiro; Saito, Takeshi; Toki, Yasumichi; Hatayama, Mayumi; Yamamoto, Masayo; Shindo, Motohiro; Takahashi, Shuichiro; Okumura, Toshikatsu","year":2025,"journal":"Neurogastroenterology and motility, 37(2), e14949","doi":"10.1111/nmo.14949","pmid":"39450642","tags":[],"studyType":"animal","evidenceStrength":"low","keyFinding":"The brain-gut regulation of intestinal barrier function involves two distinct mechanisms — one dependent on the spleen and one independent. When neuropeptides orexin, ghrelin, or oxytocin are injected into the brain, they improve intestinal barrier function through a pathway that requires the spleen. However, GLP-1 (via liraglutide) acts through a separate spleen-independent pathway via vagal cholinergic signaling.\n\nIn splenectomized rats, orexin, ghrelin, and oxytocin lost their ability to reduce gut permeability, while liraglutide maintained its dose-dependent protective effect through atropine-sensitive (cholinergic) vagal mechanisms.","whyItMatters":"Leaky gut (increased intestinal permeability) is implicated in many diseases from inflammatory bowel disease to autoimmune conditions. This study reveals that GLP-1 drugs like liraglutide can strengthen the gut barrier through a direct brain-to-gut neural pathway — a mechanism entirely separate from how other neuropeptides work. This adds gut barrier protection to GLP-1's growing list of beneficial effects.","specificNumbers":"4 neuropeptides tested · Splenectomy blocked orexin, ghrelin, oxytocin effects · Liraglutide effective in dose-dependent manner · Blocked by atropine · Dual brain-gut mechanisms identified","methodology":"Animal study in rats measuring colonic permeability in vivo using Evans blue absorption. Splenectomized and sham-operated rats received intracisternal (brain) injections of orexin, ghrelin, oxytocin, butyrate, or liraglutide. Vagal cholinergic mechanisms were tested using carbachol, 2-deoxy-d-glucose, and the blocker atropine. GLP-1 receptor antagonist was used to confirm receptor specificity.","limitations":"Rat study — brain-gut barrier regulation may differ in humans. Intracisternal injection is not a clinically relevant route of administration. The study measures colonic permeability with a single dye method, which captures one aspect of barrier function. Whether systemically administered GLP-1 drugs produce the same gut barrier effects is not addressed."},{"rthcId":"RPEP-11002","title":"The Effects of Semaglutide on Inflammation and Immune Activation in HIV-associated Lipohypertrophy.","authors":"Funderburg, Nicholas T; Ross Eckard, Allison; Wu, Qian; Sattar, Abdus; Ailstock, Kate; Cummings, Morgan; Labbato, Danielle; McComsey, Grace A","year":2025,"journal":"Open forum infectious diseases, 12(4), ofaf152","doi":"10.1093/ofid/ofaf152","pmid":"40160348","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"After 32 weeks of weekly subcutaneous semaglutide (1.0 mg), participants showed significant reductions in C-reactive protein (CRP), interleukin-6 (IL-6), and soluble CD163 (sCD163) compared to baseline — all markers strongly linked to cardiovascular risk and mortality in people with HIV. Soluble CD14 showed a trend toward reduction (P = .08). Importantly, monocyte proportions and T-cell phenotypes remained unchanged, suggesting the anti-inflammatory effect operates through pathways other than direct immune cell modulation.","whyItMatters":"Chronic inflammation is a major driver of cardiovascular disease and premature death in people with HIV, even when viral load is well-controlled. Finding treatments that can reduce this inflammation — beyond what antiretroviral therapy alone achieves — could meaningfully improve long-term outcomes. This trial provides randomized evidence that semaglutide has anti-inflammatory properties relevant to this high-risk population.","specificNumbers":"","methodology":"This was a single-site, randomized, double-blinded, placebo-controlled trial. Researchers enrolled 108 virologically suppressed, non-diabetic adults with HIV who had a BMI of 25 or higher and increased abdominal girth after starting antiretroviral therapy. Participants were split evenly into semaglutide and placebo groups for 32 weeks, with an 8-week dose titration period followed by 24 weeks at the full 1.0 mg weekly dose. Blood markers of inflammation and immune cell phenotypes were measured at baseline and after treatment.","limitations":"The trial was conducted at a single site, which may limit generalizability. The 15% dropout rate in each group could introduce some bias. The study measured surrogate markers of inflammation rather than hard clinical endpoints like heart attacks or strokes. Monocyte and T-cell analyses showed no changes, leaving the precise anti-inflammatory mechanism unclear. The 32-week duration may not capture long-term effects."},{"rthcId":"RPEP-11003","title":"Rhabdomyolysis triggered by initiation of tirzepatide.","authors":"Fushimi, Yoshiro; Kimura, Tomohiko; Sanada, Junpei; Shimoda, Masashi; Nakanishi, Shuhei; Kaneto, Hideaki","year":2025,"journal":"Diabetology international, 16(3), 591-594","doi":"10.1007/s13340-025-00825-x","pmid":"40607146","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11004","title":"Patient experiences with liraglutide for obesity and binge eating disorder-A qualitative study.","authors":"Følling, Ingrid Sørdal; Reigstad, Stine Larsen; Hyldmo, Åsne Ask; Helvik, Anne-Sofie","year":2025,"journal":"PloS one, 20(10), e0335806","doi":"10.1371/journal.pone.0335806","pmid":"41171863","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11005","title":"Botulinum Neurotoxin A Signaling in Pain Modulation Within Human Sensory Neurons.","authors":"Gabriel, Katherin A; Hankerd, Kali; Barragan-Iglesias, Paulino; Brideau-Andersen, Amy D; Steward, Lance E; McGaraughty, Steve; Vazquez-Cintron, Edwin; Price, Theodore J","year":2025,"journal":"Journal of neurochemistry, 169(9), e70236","doi":"10.1111/jnc.70236","pmid":"40956003","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11006","title":"Insights into the Roles of GLP-1, DPP-4, and SGLT2 at the Crossroads of Cardiovascular, Renal, and Metabolic Pathophysiology.","authors":"Gaggini, Melania; Sabatino, Laura; Suman, Adrian Florentin; Chatzianagnostou, Kyriazoula; Vassalle, Cristina","year":2025,"journal":"Cells, 14(5)","doi":"10.3390/cells14050387","pmid":"40072115","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11007","title":"SGLT2 Inhibitors and GLP-1 Receptor Agonists in Cardiovascular-Kidney-Metabolic Syndrome.","authors":"Gajjar, Aryan; Raju, Arvind Kumar; Gajjar, Amani; Menon, Mythili; Shah, Syed Asfand Yar; Dani, Sourbha; Weinberg, Andrew","year":2025,"journal":"Biomedicines, 13(8)","doi":"10.3390/biomedicines13081924","pmid":"40868177","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11008","title":"Breaking the weight loss paradox: from weight reduction to cardiovascular benefit in obesity treatment.","authors":"Gajos, Grzegorz","year":2025,"journal":"Polish archives of internal medicine, 135(3)","doi":"10.20452/pamw.16983","pmid":"40126003","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review highlights the paradigm shift in obesity pharmacotherapy driven by peptide-based drugs:\n\n- Semaglutide: first obesity drug to demonstrate a significant 20% reduction in major adverse cardiovascular events (MACE) in the SELECT trial, though secondary endpoints were neutral\n- Tirzepatide and retatrutide: next-generation multi-receptor agonists achieving up to 24% weight loss\n- These drugs exert pleiotropic effects beyond weight loss: anti-inflammatory properties, improved endothelial function, and anti-atherosclerotic effects that may contribute to cardiovascular protection\n- Lifestyle modifications, while foundational, have limited long-term efficacy as most individuals regain lost weight\n- Bariatric surgery remains most effective for long-term weight management but has limited accessibility","whyItMatters":"Obesity affects over 1 billion people worldwide and is the leading modifiable risk factor for cardiovascular disease. The fact that semaglutide — a peptide drug — is the first obesity medication to prove cardiovascular risk reduction is a watershed moment in medicine. It validates the entire approach of using incretin-based peptide therapeutics not just for weight loss but for cardiovascular protection, potentially saving millions of lives.","specificNumbers":"","methodology":"Narrative review synthesizing clinical trial data, cardiovascular outcome studies (including SELECT), and emerging research on next-generation obesity pharmacotherapies. The review covers the evolution from lifestyle interventions and bariatric surgery to GLP-1 receptor agonists and multi-receptor agonists.","limitations":"As a narrative review, this synthesizes existing literature without new data. The SELECT trial's neutral secondary endpoints warrant caution about the breadth of cardiovascular benefit. The newest agents (retatrutide) have weight loss data but lack completed cardiovascular outcome trials. Long-term safety data (beyond 2-3 years) is limited for most agents. Cost and access remain significant barriers to widespread adoption of these expensive peptide drugs."},{"rthcId":"RPEP-11009","title":"The Beneficial Effects of Glucagon-Like Peptide-1 Agonists on Blood Pressure: A Comprehensive Review.","authors":"Gala, Dhir; Botros, Fady; Makaryus, Amgad N","year":2025,"journal":"Reviews in cardiovascular medicine, 26(12), 45204","doi":"10.31083/RCM45204","pmid":"41524068","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11010","title":"Esophageal high-resolution manometry can be safely and effectively performed with concurrent glucagon-like peptide-1 receptor agonist use.","authors":"Gala, Khushboo; Chopra, Preeyati; Ohri, Ashwariya; Goyal, Mayank; Marek, George; Camilleri, Michael; Ravi, Karthik","year":2025,"journal":"Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus, 38(6)","doi":"10.1093/dote/doaf109","pmid":"41343723","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11011","title":"Glucagon-like Peptide-1 Receptor Agonist Use Is Associated With and May Lead to Esophageal Motility Abnormalities.","authors":"Gala, Khushboo; Camilleri, Michael; Goyal, Mayank; Ohri, Ashwariya; Marek, George; Ravi, Karthik","year":2025,"journal":"Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association","doi":"10.1016/j.cgh.2025.11.003","pmid":"41213390","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11012","title":"Association of preoperative Circulating biomarkers with echocardiographic measures of right ventricular strain five years after tetralogy of fallot repair.","authors":"Galan, Jose A; Faerber, Jennifer A; Jones, Andrea L; Numata, Ryusuke; Thomas, Angeli; Mai, Anh Duc; Wang, Yan; Himebauch, Adam S; Gardner, Monique M; Mercer-Rosa, Laura","year":2025,"journal":"The international journal of cardiovascular imaging, 41(11), 2229-2239","doi":"10.1007/s10554-025-03533-4","pmid":"41144173","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11013","title":"Improvement in body mass index category was associated with improved cardiometabolic measures and patient-reported outcomes in adults with type 2 diabetes treated with tirzepatide.","authors":"Galindo, Rodolfo J; Lee, Clare J; Allen, Sheryl Elaine; Dib, Anne; Boye, Kristina S; Thieu, Vivian Thuyanh; Dong, Wenxiu; Sapin, Hélène; Wiese, Russell J","year":2025,"journal":"Diabetes, obesity & metabolism, 27(10), 5694-5705","doi":"10.1111/dom.16620","pmid":"40707399","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across the pooled SURPASS-1 through -5 trial data (3,559 participants), 58.9% of tirzepatide-treated adults with type 2 diabetes shifted to an improved (lower) BMI category at weeks 40-52, while 41.1% remained in the same or a worsened category.\n\nParticipants who improved their BMI category showed numerically larger mean improvements from baseline in the majority of selected cardiometabolic parameters across all five trials compared to those who did not improve. Weight-related patient-reported outcomes were also numerically best in the improved BMI group, suggesting that meaningful BMI category shifts translate to both objective health improvements and subjective quality-of-life benefits.","whyItMatters":"BMI category changes are clinically meaningful benchmarks — moving from obesity class II to class I, or from obese to overweight, represents real thresholds that affect treatment guidelines, surgical eligibility, and disease risk. Showing that tirzepatide drives these category shifts in the majority of patients reinforces its potential to meaningfully change patients' health trajectories.","specificNumbers":"","methodology":"Post-hoc analysis of pooled data from SURPASS-1 through SURPASS-5, five Phase 3 randomized controlled trials of weekly tirzepatide in adults with type 2 diabetes. All tirzepatide doses were pooled. BMI changes were categorized as 'improved' (shift to one or more lower BMI categories) or 'not improved' (stable or worsened) from baseline to week 40 or 52. Associations with cardiometabolic parameters and weight-related patient-reported outcomes were assessed.","limitations":"This is a post-hoc analysis, which means the trials were not originally designed to assess BMI category shifts as a primary endpoint. Improvements in cardiometabolic parameters were described as numerical (not always statistically significant) differences. The analysis pooled all tirzepatide doses, obscuring potential dose-response relationships. There was no placebo comparison in this specific BMI shift analysis."},{"rthcId":"RPEP-11014","title":"Impact of novel amino acid substituted and acylated spexin analogues on pancreatic beta-cell function, appetite and glucose homeostasis.","authors":"Gallagher, Daniel M; Khan, Md Zahidul Islam; Patterson, Steven; O'Harte, Finbarr P M; Irwin, Nigel","year":2025,"journal":"Molecular and cellular endocrinology, 609, 112657","doi":"10.1016/j.mce.2025.112657","pmid":"40953657","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11015","title":"Bioactive Plasmid- and Phage-Encoded Antimicrobial Peptides (AMPs) in the Human Gut: A Metatranscriptome-Virome Profiling Reveals Exploratory Links to Metabolic Human Diseases.","authors":"Gallardo-Becerra, Luigui; Cornejo-Granados, Fernanda; Bikel, Shirley; Arenas, Iván; López-Leal, Gamaliel; Alvarado-Gonzalez, Carolina; Sánchez-López, Filiberto; Manzo, Rubiceli; Corzo, Gerardo; Espino-Solis, Gerardo P; Canizales-Quinteros, Samuel; Ochoa-Leyva, Adrian","year":2025,"journal":"Microbial ecology, 89(1), 15","doi":"10.1007/s00248-025-02620-2","pmid":"41315055","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11016","title":"Crotalicidin and NA-CATH-ATRA-1-ATRA-1 peptide-induced membrane disruption in human breast cancer cells.","authors":"Gallego-Londoño, Vanessa; Santa-González, Gloria A; Giraldo-Lorza, Juan M; Rojas, Mauricio; Wisman, G Bea A; de Jong, Steven; Manrique-Moreno, Marcela","year":2025,"journal":"Biochimica et biophysica acta. Biomembranes, 1867(5-6), 184429","doi":"10.1016/j.bbamem.2025.184429","pmid":"40490220","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11017","title":"Cardiovascular Effects and Tolerability of GLP-1 Receptor Agonists: A Systematic Review and Meta-Analysis of 99,599 Patients.","authors":"Galli, Mattia; Benenati, Stefano; Laudani, Claudio; Simeone, Beatrice; Sarto, Gianmarco; Ortega-Paz, Luis; Rocco, Erica; Bernardi, Marco; Spadafora, Luigi; D'Amario, Domenico; Greco, Ernesto; Frati, Giacomo; Federici, Massimo; Mehran, Roxana; Crea, Filippo; Angiolillo, Dominick J; Sciarretta, Sebastiano","year":2025,"journal":"Journal of the American College of Cardiology, 86(20), 1805-1819","doi":"10.1016/j.jacc.2025.08.027","pmid":"40892610","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11018","title":"GLP-2 and GIP acutely increase superior mesenteric artery blood flow in male rats, and the effect is independent of nitric oxide and vasoactive intestinal peptide.","authors":"Galsgaard, Katrine D; Hartmann, Bolette; Rosenkilde, Mette M; Holst, Jens J; Gasbjerg, Lærke S; Sørensen, Charlotte M","year":2025,"journal":"Physiological reports, 13(23), e70699","doi":"10.14814/phy2.70699","pmid":"41388842","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Both GLP-2 and GIP independently increased blood flow through the superior mesenteric artery (the main blood vessel feeding the intestines) in anesthetized rats. Surprisingly, this effect did not depend on nitric oxide or vasoactive intestinal peptide — two of the most commonly assumed mediators of gut blood flow. Combining the two peptides or using a novel dual GIP/GLP-2 co-agonist did not produce a synergistic (greater-than-additive) effect. The GLP-2 receptor antagonist GLP-2(3-33) successfully blocked GLP-2's blood flow effect, confirming it acts through the GLP-2 receptor.","whyItMatters":"After you eat a meal, blood flow to your intestines increases dramatically to help absorb nutrients. GLP-2 and GIP are gut hormones released after eating that were suspected of driving this response, but the mechanism wasn't clear. This study confirms both peptides boost intestinal blood flow and — importantly — rules out two of the most obvious pathways (nitric oxide and VIP), meaning there's an unknown mechanism at work. Understanding this could be relevant for conditions like short bowel syndrome, where GLP-2 analogs are already used as drugs.","specificNumbers":"","methodology":"Researchers used anesthetized male Sprague-Dawley rats with transit-time flow probes surgically placed on the superior mesenteric artery to directly measure blood flow in real time. They administered GLP-2, GIP, or a novel dual co-agonist and measured acute blood flow changes. To test potential mechanisms, they pre-treated rats with a nitric oxide synthase inhibitor (L-NAME) or a VIP receptor antagonist before giving the peptides. They also tested the GLP-2 receptor antagonist GLP-2(3-33).","limitations":"This was an animal study in anesthetized rats, which may not fully reflect how these peptides work in awake animals or humans. Anesthesia itself can affect cardiovascular responses. The study used male rats only, so sex-specific differences weren't explored. The doses used were pharmacological rather than physiological, and the acute timeframe doesn't capture longer-term vascular adaptations."},{"rthcId":"RPEP-11019","title":"In Vivo Inhibition of Dipeptidyl Peptidase 4 and Neprilysin Activity Enables Measurement of GLP-1 Secretion in Male Rats.","authors":"Galsgaard, Katrine D; Abba, Valentina; Kuhre, Rune E; Holst, Jens J; Hartmann, Bolette","year":2025,"journal":"Journal of the Endocrine Society, 9(12), bvaf173","doi":"10.1210/jendso/bvaf173","pmid":"41278011","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11020","title":"Genome-Wide Identification of the Defensin Gene Family in Triticum durum and Assessment of Its Response to Environmental Stresses.","authors":"Gamas, Nawress; Smaoui, Fahmi; Ben Romdhane, Walid; Wiszniewska, Alina; Baazaoui, Narjes; Bouteraa, Mohamed Taieb; Chouaibi, Yosra; Ben Hsouna, Anis; Kačániová, Miroslava; Kluz, Maciej Ireneusz; Garzoli, Stefania; Ben Saad, Rania","year":2025,"journal":"Biology, 14(4)","doi":"10.3390/biology14040404","pmid":"40282269","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11021","title":"Long-term cancer risk in users of GLP-1 agonists in Denmark: a nationwide emulated trial.","authors":"Gamborg, Mads; Grand, Mia Klinten; Grell, Kathrine; Rosthøj, Susanne; Pedersen-Bjergaard, Ulrik; Torp-Pedersen, Christian; Mørch, Lina Steinrud","year":2025,"journal":"The Lancet regional health. Europe, 55, 101346","doi":"10.1016/j.lanepe.2025.101346","pmid":"40950945","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11022","title":"Metabolic resilience: liraglutide's potential in alleviating depressive symptoms.","authors":"Gammoh, Omar; Qnais, Esam; Aljabali, Alaa A A; Hatahet, Taher; Alqudah, Abdelrahim","year":2025,"journal":"Molecular biology reports, 52(1), 550","doi":"10.1007/s11033-025-10641-w","pmid":"40471368","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11023","title":"Cancer vaccine overcomes immune evasion of nasopharyngeal carcinoma by restoring MHC-I through transcriptional regulation of NLRC5.","authors":"Gan, Chai Phei; Kok, Sau Yee; Lee, Bernard Kok Bang; Zulaziz, Natasha; Cheong, Sok Ching; Savelyeva, Natalia; Lim, Kue Peng","year":2025,"journal":"Journal of translational medicine, 23(1), 1414","doi":"10.1186/s12967-025-07418-x","pmid":"41437275","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A peptide-based cancer vaccine overcomes immune evasion in nasopharyngeal carcinoma by restoring the cell's antigen presentation machinery. Peptide-trained T cells upregulated NLRC5 (the most downregulated gene in NPC tumors), restored MHC-I expression, and enhanced tumor cell killing — even in cells where NLRC5 had been experimentally knocked down. The vaccine approach was validated in a mouse tumor model, showing consistent restoration of antigen presentation gene expression in vivo.","whyItMatters":"Many cancers escape the immune system by hiding their surface markers (MHC-I), making them invisible to T cells. This study shows that a peptide vaccine can actually force cancer cells to re-expose these markers by reactivating the silenced NLRC5 gene. This is particularly important because it means peptide vaccines could work even against tumors that have evolved to evade immunity — a major barrier to immunotherapy success.","specificNumbers":"42 NPC tumors + 4 non-NPC tissues analyzed · 17-gene APM signature · NLRC5 most downregulated · MHC-I downregulated in 63% of tumors · 35 tumors by IHC · siRNA NLRC5 knockdown reversed by peptide-trained T cells · validated in vivo","methodology":"Researchers analyzed 42 NPC tumors for antigen presentation machinery (APM) gene expression using a 17-gene signature. MHC-I expression was assessed by immunohistochemistry in 35 tumors. Peptide-trained T cells were co-cultured with NPC cells to study APM gene modulation. A siRNA-mediated NLRC5 knockdown model tested whether vaccine-induced T cells could reverse immune evasion. In vivo validation used a poorly immunogenic mouse tumor model.","limitations":"The in vitro co-culture system is simplified compared to the tumor microenvironment. The study focused on nasopharyngeal carcinoma and may not apply to all cancer types with MHC-I downregulation. The specific peptide antigens used for T cell training were not detailed in the abstract. Long-term durability of the restored antigen presentation and sustained anti-tumor response were not assessed."},{"rthcId":"RPEP-11024","title":"Severe euglycemic ketoacidosis following combined therapy with GLP-1 receptor agonist and SGLT-2 inhibitor, refractory to standard treatment: a case report.","authors":"Gandecka-Pempera, Agnieszka; Naskręt, Dariusz; Adamska, Anna; Zozulińska-Ziółkiewicz, Dorota","year":2025,"journal":"Frontiers in endocrinology, 16, 1649270","doi":"10.3389/fendo.2025.1649270","pmid":"41127515","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11025","title":"Erenumab in a patient with persistent headaches after subarachnoid hemorrhage: A case report of an effective treatment.","authors":"Gandhi, Ajay; Quinoa, Travis R; Geller, Eric; Khandelwal, Priyank; Agarwalla, Pankaj K","year":2025,"journal":"Headache, 65(2), 373-376","doi":"10.1111/head.14884","pmid":"39865710","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11026","title":"Comparative Renal Safety of Tirzepatide and Semaglutide: An FDA Adverse Event Reporting System (FAERS)-Disproportionality Study.","authors":"Gandhi, Ayush; Bhatt, Nilay; Parhizgar, Alireza","year":2025,"journal":"Journal of clinical medicine, 14(21)","doi":"10.3390/jcm14217678","pmid":"41227073","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11027","title":"GLP-1 receptor agonists in Alzheimer's and Parkinson's disease: endocrine pathways, clinical evidence, and future directions.","authors":"Gandhi, Ayush; Parhizgar, Alireza","year":2025,"journal":"Frontiers in endocrinology, 16, 1708565","doi":"10.3389/fendo.2025.1708565","pmid":"41356006","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Preclinical: GLP-1RAs reduce neuroinflammation, improve mitochondrial function, and enhance clearance of toxic proteins in both AD and PD models, leading to improved cognition and dopaminergic neuron survival.\n\nClinical — Parkinson's: Exenatide and lixisenatide demonstrated motor benefits in trials. However, NLY01 (pegylated exendin) did not meet its primary endpoint, showing not all GLP-1RAs perform equally.\n\nClinical — Alzheimer's: Mixed cognitive outcomes in early trials, but liraglutide preserved cerebral glucose metabolism on FDG-PET scans — an intriguing biological effect suggesting neuroprotection even without clear cognitive benefit.\n\nThe EVOKE and EVOKE+ Phase 3 trials with semaglutide are the definitive tests that could establish GLP-1RAs as neurodegenerative disease treatments.","whyItMatters":"Alzheimer's and Parkinson's diseases affect tens of millions globally with limited treatment options. Finding that GLP-1 drugs — already proven safe in millions of diabetes and obesity patients — could modify neurodegenerative disease course would be transformative. The existing safety and manufacturing infrastructure means these drugs could be rapidly deployed if efficacy is confirmed, unlike entirely new drug candidates that require years of development.","specificNumbers":"","methodology":"Narrative review of preclinical evidence (animal models of AD and PD), early clinical trial results, and ongoing clinical trials for GLP-1 receptor agonists in neurodegenerative diseases. The review covers endocrine pathways, CNS mechanisms, and clinical evidence across multiple GLP-1RA agents.","limitations":"This is a narrative review, not a systematic review. Preclinical promise has often failed to translate to clinical benefit in neurodegeneration (the 'translational gap'). Early AD clinical trials have had mixed cognitive results. Not all GLP-1RAs appear equally effective (NLY01 failed in PD). Brain penetration varies between GLP-1RAs, which may explain different outcomes. The EVOKE trials have not yet reported results. Long-term CNS effects of chronic GLP-1RA use are unknown."},{"rthcId":"RPEP-11028","title":"Semaglutide Treatment of Antipsychotic-Treated Patients With Schizophrenia, Prediabetes, and Obesity: The HISTORI Randomized Clinical Trial.","authors":"Ganeshalingam, Ashok A; Uhrenholt, Nicolai; Arnfred, Sidse; Gæde, Peter; Düring, Signe; Stenager, Elsebeth N; Bünger, Nick; Pedersen, Andreas K; Bilenberg, Niels; Frystyk, Jan","year":2025,"journal":"JAMA psychiatry, 82(11), 1065-1074","doi":"10.1001/jamapsychiatry.2025.2332","pmid":"40900607","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 154 antipsychotic-treated schizophrenia patients with prediabetes and obesity, semaglutide (up to 1.0 mg/week for 30 weeks) versus placebo:\n- HbA1c reduced by 0.46% (95% CI -0.56 to -0.36)\n- Body weight reduced by 9.21 kg (95% CI -11.68 to -6.75)\n- 81% vs 19% achieved HbA1c <5.7% (prediabetes reversal, p<0.001)\n- HDL cholesterol improved by 10.81 mg/dL (p=0.007)\n- Triglycerides improved by -29.20 mg/dL (p=0.03)\n- Physical quality of life improved by 3.75 points on SF-36v2 (p=0.001)\n- No significant effect on PANSS-6 schizophrenia symptom score or mental QoL\n- 96% completion rate in semaglutide group vs 87% in placebo\n- GI symptoms more common with semaglutide; serious adverse events similar between groups","whyItMatters":"This is a landmark trial for one of the most vulnerable and medically underserved populations in healthcare. Antipsychotic-induced weight gain and metabolic syndrome contribute to a 15-20 year mortality gap in schizophrenia, yet metabolic interventions have shown limited success in this group. The HISTORI trial demonstrates that semaglutide is both safe (no psychiatric worsening) and highly effective (81% prediabetes reversal, 9.21 kg weight loss) in these patients, potentially changing clinical practice for millions of antipsychotic-treated individuals worldwide.","specificNumbers":"","methodology":"Multicenter, double-blinded, placebo-controlled randomized clinical trial (HISTORI) conducted January 2022 to May 2024 across community-based mental health services in two Danish regions. 154 SGA-treated adults (18-60 years) with schizophrenia, prediabetes (HbA1c 5.7-6.4%), and BMI ≥27 were randomized 1:1 to semaglutide (titrated to 1.0 mg/week over 8 weeks) or placebo for 30 weeks. Primary outcome: HbA1c change. ClinicalTrials.gov: NCT05193578.","limitations":"The study used semaglutide up to 1.0 mg/week (not the higher 2.4 mg used for obesity treatment), so weight loss may be even greater at higher doses. The 30-week duration doesn't address long-term outcomes or what happens after stopping semaglutide. A few more hospitalizations were noted in the semaglutide group, though serious adverse events were similar between groups. The study population was from Denmark, and results may vary in other populations. Mental QoL did not improve, suggesting semaglutide's benefits are primarily metabolic rather than psychiatric."},{"rthcId":"RPEP-11029","title":"Antimicrobial peptides: An alternative strategy to combat antimicrobial resistance.","authors":"Gani, Zahid; Kumar, Ajay; Raje, Manoj; Raje, Chaaya Iyengar","year":2025,"journal":"Drug discovery today, 30(2), 104305","doi":"10.1016/j.drudis.2025.104305","pmid":"39900281","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11030","title":"Swiss Quality of Life and Health Care Impact Assessment in a Real-World Erenumab-Treated Migraine Population: Results over 2 years.","authors":"Gantenbein, Andreas R; Kamm, Christian P; Schankin, Christoph J; Zecca, Chiara; Zieglgänsberger, Dominik; Pohl, Heiko; Ryvlin, Philippe; Agosti, Reto; Viceic, Dragana; Parzini, Catherine; Kulartz-Schank, Monika; Arzt, Michael E","year":2025,"journal":"Headache, 65(7), 1134-1147","doi":"10.1111/head.14943","pmid":"40304557","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Over 24 months of erenumab treatment in 173 patients (84.9% female, mean age 44.2, 45.7% chronic migraine), significant improvements were observed across all measures (all p < 0.001):\n- Monthly migraine days: decreased by 8.8 ± 7.6 (from 16.5 baseline)\n- HIT-6 headache impact: decreased by 8.1 ± 8.6 (from 65.9 baseline)\n- mMIDAS disability: decreased by 16.6 ± 21.2\n- Monthly acute medication days: decreased by 5.2 ± 6.8 (from 11.5 baseline)\n- IMPAC family burden: decreased by 6.5 ± 6.6\n\n48.6% had at least one adverse event, 35.3% had drug-related adverse events, but no serious adverse events were attributed to erenumab.","whyItMatters":"While clinical trials showed erenumab's efficacy in controlled settings, real-world evidence over 2 years is crucial for confirming sustained benefit in routine clinical practice. This study uniquely measured family impact, showing that CGRP-targeting therapy improves not just patients' lives but their families' lives too — an outcome rarely captured in migraine trials.","specificNumbers":"","methodology":"Prospective, multicenter, noninterventional cohort study across 19 Swiss sites enrolling adults with episodic or chronic migraine who received erenumab per Swiss label from February 2019 to November 2022. Data collected over 24 months included patient-reported outcomes (HIT-6, mMIDAS, IMPAC questionnaires), migraine diaries (required 3 months before and during treatment), and medical chart data on medication use and healthcare utilization.","limitations":"This is an observational cohort study without a control group, so placebo effects and natural disease fluctuation cannot be excluded. The 173-patient sample is moderate in size. The 2-year completion rate is not specified, introducing potential survivorship bias (patients who continued may be those who responded best). The Swiss healthcare context (mandated diary-keeping, label restrictions) may limit generalizability to other countries."},{"rthcId":"RPEP-11031","title":"Marine Antimicrobial Peptides: Advances in Discovery, Multifunctional Mechanisms, and Therapeutic Translation Challenges.","authors":"Gao, Bin; Yang, Na; Teng, Da; Hao, Ya; Wang, Jianhua; Mao, Ruoyu","year":2025,"journal":"Marine drugs, 23(12)","doi":"10.3390/md23120463","pmid":"41440897","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11032","title":"Depressive state on cardiac remodeling and left ventricular function in chronic heart failure: A retrospective study.","authors":"Gao, Bo; Gao, Yun-Fan; Chu, Meng-Ting; Yuan, Ke-Fang","year":2025,"journal":"World journal of psychiatry, 15(9), 106906","doi":"10.5498/wjp.v15.i9.106906","pmid":"40933172","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Heart failure patients with depression (Hamilton Depression Scale score ≥17) showed significantly worse cardiac parameters compared to non-depressed patients:\n\n- Left ventricular ejection fraction: 42.3% ± 6.7% vs 51.6% ± 5.9% (depressed vs non-depressed)\n- B-type natriuretic peptide: 1,256 ± 345 pg/mL vs 756 ± 234 pg/mL — a 66% higher level in depressed patients\n- Angiotensin II: 86.4 ± 15.7 ng/mL vs 62.5 ± 12.3 ng/mL — a 38% higher level\n- TNF-α: 42.5 ± 7.6 pg/mL vs 28.3 ± 5.4 pg/mL\n- IL-6 was also significantly elevated in the depressed cohort\n\nThese findings suggest depression accelerates cardiac remodeling and left ventricular dysfunction through inflammatory cascades and neuroendocrine overactivation.","whyItMatters":"Depression affects up to 40% of heart failure patients and is associated with worse outcomes, but the mechanisms have been unclear. This study provides specific biomarker evidence linking depression to higher levels of BNP and angiotensin II — two peptides central to heart failure pathophysiology. This suggests that treating depression in heart failure patients could reduce harmful neuroendocrine activation and slow disease progression, not just improve quality of life.","specificNumbers":"","methodology":"This was a retrospective study of 248 chronic heart failure patients treated at a tertiary care center between January 2018 and December 2022. Patients were classified as depressed or non-depressed using the Hamilton Depression Scale (cutoff score of 17). Cardiac morphology and function were assessed by echocardiography and cardiac MRI. Blood biomarkers included B-type natriuretic peptide, angiotensin II, TNF-α, and IL-6.","limitations":"This is a retrospective observational study, so it cannot prove that depression causes worse cardiac function — the relationship may be bidirectional or confounded by disease severity. The Hamilton Depression Scale is a validated but subjective measure. Medication use (antidepressants, ACE inhibitors, beta-blockers) was not controlled for in the abstract. The abstract text appears to have some formatting or translation issues that may obscure some numerical comparisons."},{"rthcId":"RPEP-11033","title":"Bifidobacterium Breve BBr60 Improves Obesity Via the Gut Microbiota-Short-Chain Fatty Acid-IL-27/GLP-1 Axis: Evidence from a Randomized, Double-Blind, Placebo-Controlled Trial.","authors":"Gao, Dejiao; Dong, Yao; Jia, Zhumin; Bian, Chenying; Zhu, Jianguo; Wu, Ying; Fang, Shuguang; Gu, Shaobin","year":2025,"journal":"Probiotics and antimicrobial proteins","doi":"10.1007/s12602-025-10885-9","pmid":"41455007","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"After 12 weeks, the BBr60 group showed significantly increased fecal butyrate levels (p < 0.001), which correlated with increased GLP-1 and IL-27 levels. Multiple metabolic peptide hormones were significantly elevated in the probiotic group: leptin, adiponectin, C-peptide, pancreatic polypeptide, peptide YY, GIP, and GLP-1 (all p < 0.05). HOMA-IR (insulin resistance) was significantly reduced (p < 0.05).\n\nThe anti-inflammatory cytokine IL-27 was upregulated (p < 0.01) while the pro-inflammatory IL-1β was decreased (p < 0.05). In the placebo group, only C-peptide, pancreatic polypeptide, and GIP increased, with no changes in leptin, adiponectin, PYY, GLP-1, or HOMA-IR. Butyrate levels positively correlated with GLP-1 and IL-27, and negatively with IL-1β.","whyItMatters":"GLP-1 receptor agonist drugs like semaglutide and tirzepatide are revolutionary for obesity, but they require injections or expensive prescriptions. This study suggests that specific probiotics can naturally boost the body's own production of GLP-1 and other metabolic peptides by improving gut health. This could offer a complementary, accessible approach to improving metabolic function in obesity.","specificNumbers":"","methodology":"A randomized, double-blind, placebo-controlled trial enrolled 75 individuals with obesity (BMI ≥ 28), with 65 completing the study (33 BBr60, 32 placebo). The intervention group received 10 billion CFU of Bifidobacterium breve BBr60 daily for 12 weeks. All participants received standardized nutritional counseling (~1800 kcal/day, 25g fiber) with weekly phone check-ins. Gut microbiota was analyzed by 16S sequencing, fecal short-chain fatty acids by GC-MS, and serum hormones and cytokines by ELISA.","limitations":"The sample size was modest (65 completers). The study was 12 weeks — long-term effects and sustainability of metabolic improvements are unknown. While many peptide hormones increased, the abstract doesn't report actual weight loss or body fat changes, making it hard to assess clinical significance. The ~1800 kcal/day dietary counseling may have contributed to results in both groups. The specific mechanisms connecting butyrate to each hormone require further investigation."},{"rthcId":"RPEP-11034","title":"Liraglutide attenuates doxorubicin-induced cardiomyocyte ferroptosis via DHHC7-mediated STAT3 palmitoylation.","authors":"Gao, Ge; Shen, Cheng; Wang, Manman; Ji, Cuiling; Fang, Fang; Jiang, Yu; Shi, Lihong; Chen, Wenqiang; Zhang, Jinguo","year":2025,"journal":"Life sciences, 379, 123912","doi":"10.1016/j.lfs.2025.123912","pmid":"40819789","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11035","title":"Neuroimmune Crosstalk in Psoriasis: Mechanisms and Therapeutic Implications.","authors":"Gao, Hanlin; Fang, Yi; Zhang, Yue; Xie, Tianyi; Chen, Zhi; Wang, Gang","year":2025,"journal":"Inflammation, 49(1), 14","doi":"10.1007/s10753-025-02385-3","pmid":"41428266","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11036","title":"Evaluation of three mechanisms of action (SGLT2 inhibitors, GLP-1 receptor agonists, and sulfonylureas) in treating type 2 diabetes with heart failure: a systematic review and network meta-analysis of RCTs.","authors":"Gao, Huize; Wei, Qian; Zou, Anqi; Yu, Keying; Song, Da; Li, Jian; Han, Huize; Liu, Aidong","year":2025,"journal":"Frontiers in endocrinology, 16, 1562815","doi":"10.3389/fendo.2025.1562815","pmid":"40556828","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11037","title":"Discovery of a Novel Anticoagulant Cystine Knot Peptide from Spider Venom Gland Transcriptome.","authors":"Gao, Jinai; Yang, Di; Wang, Wanting; Huang, Xiaoshan; Guo, Ruiyin; Cao, Kaixun; Lu, Qiumin; Wang, Ziyi; Lai, Ren; Li, Juan","year":2025,"journal":"International journal of molecular sciences, 26(20)","doi":"10.3390/ijms262010154","pmid":"41155448","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11038","title":"Intestinal L-cell mechanoreception regulates hepatic lipid metabolism through GLP-1.","authors":"Gao, Luyang; Yang, Ke; Zhao, Yawen; Zhang, Jinshan; Jiang, Shaohua; Zhang, Rujiao; He, Wenxin; Zhao, Yuhang; Ye, Qianqian; Xu, Geyang","year":2025,"journal":"Science advances, 11(22), eadv3201","doi":"10.1126/sciadv.adv3201","pmid":"40446026","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11039","title":"Identification of the enzymatic cleavage relationship between anti-aging protein α-Klotho and Alzheimer's disease biomarker BACE1.","authors":"Gao, Xiang; Sun, Zuoli; Hu, Jia; Li, Yuhong; Deng, Qi; Li, Rena","year":2025,"journal":"Journal of Alzheimer's disease : JAD, 104(2), 463-472","doi":"10.1177/13872877251317730","pmid":"39994980","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BACE1 was identified as an enzyme that cleaves α-Klotho peptide 951-981 at the F-T residues, confirmed by Coomassie blue staining, western blot, and MALDI-TOF mass spectrometry. When F-T was mutated to K-K, BACE1 could not cleave the peptide, confirming site specificity. Plasma α-Klotho was significantly lower in elderly vs. young participants (p<0.0001). In elderly adults, BACE1 and α-Klotho showed a significant positive correlation (p=0.009, r=0.469) not seen in young adults (p=0.170, r=-0.208), suggesting the BACE1/α-Klotho pathway becomes functionally relevant with aging.","whyItMatters":"α-Klotho is one of the most studied anti-aging proteins, and BACE1 is a major therapeutic target in Alzheimer's research. Discovering that BACE1 directly cleaves α-Klotho creates a new mechanistic link between aging and neurodegeneration. This could explain why α-Klotho levels drop with age and suggests that BACE1 inhibitors — already being developed for Alzheimer's — might also preserve α-Klotho levels and potentially slow aging.","specificNumbers":"","methodology":"The study recruited 30 elderly and 45 young participants. Researchers performed in vitro enzymatic digestion of α-Klotho peptide by BACE1, identifying cleavage products using Coomassie blue staining, western blot, and MALDI-TOF mass spectrometry. Site-directed mutagenesis confirmed the cleavage site. Plasma levels of both proteins were measured by ELISA, and correlations were analyzed between age groups.","limitations":"The enzymatic cleavage was demonstrated in vitro, and it remains to be confirmed that this cleavage occurs at physiologically relevant rates in vivo. The human cohort (75 participants) is relatively small for correlation analyses. The positive correlation between BACE1 and α-Klotho in elderly adults is counterintuitive if BACE1 degrades α-Klotho, suggesting more complex regulatory dynamics that need investigation."},{"rthcId":"RPEP-11040","title":"Monitoring structural change and drug release of responsive nanoparticles using polarity-sensitive fluorophores.","authors":"Gao, Yanting; McDonald, Peter W; Ritchie, Chris; Such, Georgina K","year":2025,"journal":"Chemical science, 16(48), 22933-22943","doi":"10.1039/d5sc03803k","pmid":"41079659","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11041","title":"The Effects of Recombinant Human Brain Natriuretic Peptide in Combination With Sacubitril Valsartan Sodium on Cardiac Function, Inflammatory Markers, and Oxidative Stress Indicators in Elderly Patients With Acute Left Heart Failure: A Retrospective Study.","authors":"Gao, Yibing; Cheng, Zhi","year":2025,"journal":"British journal of hospital medicine (London, England : 2005), 86(4), 1-13","doi":"10.12968/hmed.2024.0706","pmid":"40265552","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11042","title":"Electrocardiograph analysis for risk assessment of heart failure with preserved ejection fraction: A deep learning model.","authors":"Gao, Zheng; Yang, Yuqing; Yang, Zhiqiang; Zhang, Xinyue; Liu, Chao","year":2025,"journal":"ESC heart failure, 12(1), 631-639","doi":"10.1002/ehf2.15120","pmid":"39463004","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11043","title":"Plastic Surgery in the Ozempidemic: Considerations for the Timing of Body Contouring Surgery in Patients with Semaglutide-Associated Weight Loss.","authors":"Garbaccio, Noelle C; Smith, Jade E; Posso, Agustin; Schonebaum, Dorien I; Foster, Lacey; Cordero, Justin J; Foppiani, Jose; Alvarez, Angelica Hernandez; Choudry, Umar; Lin, Samuel J","year":2025,"journal":"Aesthetic plastic surgery, 49(21), 6078-6088","doi":"10.1007/s00266-025-05112-3","pmid":"40835770","tags":["glp-1","weight-loss"],"studyType":"systematic-review","evidenceStrength":"strong","keyFinding":"Weight loss on semaglutide plateaus at approximately 53 weeks (about 12 months) of treatment, with patients losing an average of 16% body weight. This plateau deviated from the greatest on-treatment weight loss by only 2%, suggesting stable weight is achieved around the 8–12 month mark — the point at which body contouring surgery may be appropriate.\n\nHowever, the review also found a major concern: after stopping semaglutide, patients regained 62.7% to 74.3% of their greatest on-treatment weight loss. Weight recurrence (defined as regaining ≥25% of lost weight) occurred as early as 12 weeks after discontinuation. This massive weight regain raises serious questions about the durability of surgical outcomes if patients stop the drug after body contouring.","whyItMatters":"As millions of people lose significant weight on semaglutide (Ozempic/Wegovy), demand for body contouring surgery to remove excess skin has surged — a phenomenon dubbed the 'Ozempidemic' in plastic surgery. This review provides the first evidence-based timing guidance, but also sounds a warning: unlike bariatric surgery weight loss (which is largely permanent), semaglutide weight loss reverses substantially after stopping the drug. Surgeons and patients need to plan accordingly.","specificNumbers":"","methodology":"Systematic review and meta-analysis of MEDLINE, Embase, Web of Science, and PubMed. From 555 identified studies, 12 RCTs and prospective observational studies met inclusion criteria, encompassing 13,947 patients. The researchers calculated time to weight loss plateau (defined as ≥1 month with <3% weight loss) and weight recurrence rates after drug discontinuation.","limitations":"Only 2 of the 12 included studies assessed weight recurrence after drug discontinuation, limiting confidence in the weight regain estimates. The review focused on semaglutide specifically — results may differ for tirzepatide or other GLP-1 drugs. Long-term outcomes of body contouring surgery performed during or after GLP-1 therapy have not yet been studied directly."},{"rthcId":"RPEP-11044","title":"Survival differences according to baseline characteristics of patient with advanced heart failure treated with levosimendan.","authors":"Garcia-Peña, Angel-Alberto; Mariño, Alejandro; Muñoz-Velandia, Oscar-Mauricio; Saa-González, Daniela","year":2025,"journal":"SAGE open medicine, 13, 20503121251357357","doi":"10.1177/20503121251357357","pmid":"40689263","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11045","title":"From rodents to humans: Conserved codistribution of dopaminergic with serotonergic neurons in the dorsal raphe nucleus and their molecular characterization.","authors":"Garcia-Verdugo, Mario; Rodríguez-Martín, Pilar; Gustincich, Stefano; Lanciego, Jose L; Murer, Mario Gustavo; Jercog, Pablo; Moratalla, Rosario","year":2025,"journal":"Neurobiology of disease, 217, 107173","doi":"10.1016/j.nbd.2025.107173","pmid":"41183746","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11046","title":"Concomitant anti-CGRP and immunomodulatory treatments in patients with migraine: towards integrated management strategies.","authors":"García-Castillo, María Clara; Sierra-Mencía, Álvaro; Caronna, Edoardo; Toledo-Alfocea, Daniel; Jaimes, Alex; Urtiaga, Saray; Casas-Limón, Javier; Muñoz-Vendrell, Albert; Santos-Lasaosa, Sonia; García Martín, Valvanuz; Martín Ávila, Guillermo; Polanco, Marcos; Villar-Martínez, Maria Dolores; Trevino-Peinado, Cristina; Rubio-Flores, Laura; Sánchez-Soblechero, Antonio; Portocarrero Sánchez, Leonardo; Luque-Buzo, Elisa; Lozano-Ros, Alberto; Gago-Veiga, Ana Beatriz; Díaz-De-Terán, Javier; Recio García, Andrea; Canales Rodríguez, Javiera; Gómez García, Andrea; González Salaices, Marta; Campoy, Sergio; Mínguez-Olaondo, Ane; Maniataki, Stefania; González-Quintanilla, Vicente; Porta-Etessam, Jesús; Cuadrado, María-Luz; Guerrero Peral, Ángel Luis; Pozo-Rosich, Patricia; Rodríguez-Vico, Jaime; Huerta-Villanueva, Mariano; Pascual, Julio; Goadsby, Peter J; Gonzalez-Martinez, Alicia","year":2025,"journal":"Journal of neurology, 272(6), 443","doi":"10.1007/s00415-025-13177-y","pmid":"40461909","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11047","title":"Beyond GLP-1 Agonists: An Adaptive Ketogenic-Mediterranean Protocol to Counter Metabolic Adaptation in Obesity Management.","authors":"García-Gorrita, Cayetano; San Onofre, Nadia; Merino-Torres, Juan F; Soriano, Jose M","year":2025,"journal":"Nutrients, 17(16)","doi":"10.3390/nu17162699","pmid":"40871728","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11048","title":"Novel hepcidin genes in gilthead seabream: Implications for immune response and iron metabolism.","authors":"García-Navarro, Laura; Serna-Duque, Jhon A; Cuesta, Alberto; Esteban, M Ángeles","year":2025,"journal":"Microbial pathogenesis, 205, 107695","doi":"10.1016/j.micpath.2025.107695","pmid":"40373941","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11049","title":"Spirocyclopentane as a Novel Scaffold for Potent Ghrelin Receptor Full Agonists.","authors":"Gardelli, Cristina; Llinas, Antonio; Shamovsky, Igor; Xiong, Yao; Chen, Rongfeng; Caffrey, Moya; Hidestål, Lotta; Ray, Asim; Cooper, Martin; Jellesmark Jensen, Tina; Hultin, Leif; Andersson, Ulf; Lundqvist, Sara; Lindberg, Botilda; Douglasson, Helena; Krutrök, Nina; Pettersen, Anna; Lewis, Richard; Jansson, Paul","year":2025,"journal":"Journal of medicinal chemistry, 68(24), 26061-26084","doi":"10.1021/acs.jmedchem.5c02097","pmid":"41347768","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11050","title":"Exploring the Utility of Cell-Penetrating Peptides as Vehicles for the Delivery of Distinct Antimalarial Drug Cargoes.","authors":"Gare, Caitlin L; Palombi, Isabella R; White, Andrew M; Chavchich, Marina; Edstein, Michael D; Lock, Aaron; Avery, Vicky M; Craik, David J; McMorran, Brendan J; Lawrence, Nicole; Malins, Lara R","year":2025,"journal":"ChemMedChem, 20(2), e202400637","doi":"10.1002/cmdc.202400637","pmid":"39379289","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11051","title":"From lead to market: chemical approaches to transform peptides into therapeutics.","authors":"Gare, Caitlin L; White, Andrew M; Malins, Lara R","year":2025,"journal":"Trends in biochemical sciences, 50(6), 467-480","doi":"10.1016/j.tibs.2025.01.009","pmid":"40011178","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11052","title":"Calcitonin gene-related peptide and headache: Comparison of two commonly used assay kits highlights the perils of measuring neuropeptides with enzyme-linked immunosorbent assays.","authors":"Garelja, Michael L; Rees, Tayla A; Hay, Debbie L","year":2025,"journal":"Headache, 65(10), 1744-1753","doi":"10.1111/head.15011","pmid":"40772530","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11053","title":"Adenoma and Sessile Serrated Polyp Detection Rates in Adults Using Glucagon-Like Peptide-1 Receptor Agonists.","authors":"Garg, Samita; Hoxha, Din; Long, David; Valencia, Sara; Yang, Qijun; Lembo, Anthony; Vargo, John J; Chiang, Dian-Jung","year":2025,"journal":"Clinical and translational gastroenterology, 16(11), e00913","doi":"10.14309/ctg.0000000000000913","pmid":"40874603","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11054","title":"All-Cause Mortality and Gastrointestinal Adverse Effects in Adults With Type 2 Diabetes on Glucagon-Like Peptide-1 Receptor Agonists vs Sodium-Glucose Cotransporter-2 Inhibitors.","authors":"Garg, Samita; Qapaja, Thabet; Hamid, Osama; Kaya, Gizem; Abdel-Razeq, Rashid; Alayan, Dina; Abu-Rumaileh, Mohammed; Lembo, Anthony; Nissen, Steven","year":2025,"journal":"Gastro hep advances, 4(10), 100736","doi":"10.1016/j.gastha.2025.100736","pmid":"40917760","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"At 24-month follow-up, GLP-1 receptor agonist users had significantly reduced all-cause mortality compared to SGLT-2 inhibitor users (OR 0.83, 95% CI: 0.80-0.87), representing a 17% relative reduction.\n\nHowever, GLP-1RA users had higher odds of gastroparesis (aOR 1.24, 95% CI: 1.11-1.38) and gastroesophageal reflux disease (aOR 1.14, 95% CI: 1.11-1.18). Notably, the risk of acute pancreatitis was lower in the GLP-1RA group, alleviating a longstanding safety concern for this drug class.","whyItMatters":"Both GLP-1 receptor agonists and SGLT-2 inhibitors are first-line diabetes treatments with cardiovascular benefits, so understanding their comparative safety profile matters enormously for prescribing decisions. This study provides the largest real-world head-to-head comparison of their GI safety profiles while also revealing a significant mortality benefit for GLP-1 drugs. The trade-off — lower death risk but more digestive side effects — is critical information for patients and clinicians choosing between these drug classes.","specificNumbers":"","methodology":"This retrospective cohort study used electronic health records from the TriNetX Multi-Institutional Database covering January 2021 through December 2022. From 3.2 million adults with type 2 diabetes, 104,947 GLP-1RA users were propensity-score matched 1:1 with SGLT-2i users to balance baseline characteristics. After matching, the groups had similar mean age (62±12 years) and HbA1c (8.0±2.0%). About 30% of participants were from underrepresented minority groups. Adjusted odds ratios were calculated for GI adverse events and all-cause mortality at 24 months.","limitations":"The retrospective observational design cannot establish causation. Despite propensity score matching, residual confounding may exist — for example, patients prescribed GLP-1RAs vs. SGLT-2is may differ in ways not captured in electronic health records. The study used diagnosis codes for GI outcomes, which may underestimate conditions like mild gastroparesis or GERD that go undiagnosed. The 2021-2022 timeframe means the study primarily captured older GLP-1RA formulations and may not reflect current prescribing patterns."},{"rthcId":"RPEP-11055","title":"All-Cause Mortality and Health Care Resource Utilization in Patients with Type 1 Diabetes Treated with Glucagon-like Peptide 1 Receptor Agonists/Glucose-Dependent Insulinotropic Polypeptide.","authors":"Garg, Samita; Kim, Sarah; Ford, Andrew; Loesch, Jack; Valencia, Sara; Zhou, Keren; Lembo, Anthony","year":2025,"journal":"Diabetes technology & therapeutics","doi":"10.1177/15209156251403555","pmid":"41468099","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11056","title":"Cardiovascular and Renal Biomarkers in Overweight and Obese Adults with Type 1 Diabetes Treated with Tirzepatide for 21 Months.","authors":"Garg, Satish K; Kaur, Gurleen; Renner, Drew; Lanning, Monica S; Mason, Emma; Beatson, Christie; Ciesco, Kelly; Snell-Bergeon, Janet","year":2025,"journal":"Diabetes technology & therapeutics, 27(3), 152-160","doi":"10.1089/dia.2024.0481","pmid":"40098470","tags":[],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"Over 21 months, 84 overweight/obese adults with type 1 diabetes using tirzepatide off-label lost an average of 59 pounds (23.4% body weight), while matched controls gained 1.7 pounds. HbA1c dropped 0.50% more in tirzepatide users versus controls. Beyond weight and blood sugar, tirzepatide significantly improved total cholesterol, LDL, triglycerides, systolic blood pressure, and preserved kidney function (eGFR).\n\nRemarkably, the cardiovascular and kidney benefits remained statistically significant even after adjusting for weight loss and HbA1c changes — suggesting tirzepatide has direct protective effects on the heart and kidneys independent of its metabolic benefits. Controls saw significant eGFR decline over the same period.","whyItMatters":"This is among the first long-term real-world data on tirzepatide use in type 1 diabetes, where it is not approved. Nearly two-thirds of adults with T1D are now overweight or obese, contributing to cardiovascular disease and kidney problems — yet they have few drug options beyond insulin. The finding that tirzepatide produced 23% weight loss, improved cardiovascular biomarkers, and preserved kidney function independently of metabolic improvements makes a compelling case for formal clinical trials.","specificNumbers":"n=84 tirzepatide, n=38 controls · Weight loss: -59 lbs (-23.4%) vs +1.7 lbs · HbA1c: -0.50% vs -0.24% (p=0.017) · Improved: LDL, total cholesterol, triglycerides, systolic BP · eGFR preserved in tirzepatide, declined in controls · Duration: 21 months · Baseline BMI: 35.2 vs 33.3","methodology":"Retrospective chart review of 84 overweight/obese adults with T1D prescribed tirzepatide since July 2022 (minimum 6 months use) at a university hospital. Controls (n=38) were frequency-matched for age, diabetes duration, sex, HbA1c, and BMI. Data from electronic medical records over 21 months. Linear mixed effects models examined changes in lipids, blood pressure, and eGFR over time, including models adjusted for weight and HbA1c changes.","limitations":"Retrospective observational design — not a randomized controlled trial, so confounding factors may explain some results. Tirzepatide users may have been more motivated or had different healthcare utilization patterns. Relatively small sample (84 + 38 controls) from a single center. Off-label prescribing means dosing may have varied. The study cannot prove causation for the weight-independent cardiovascular and kidney benefits."},{"rthcId":"RPEP-11057","title":"Efficacy and Safety of GLP-1 Receptor Agonists and SGLT-2 Inhibitors in the Treatment of Diabetes Mellitus and Obesity in Liver Transplant Recipients: A Systematic Review.","authors":"Garlatti Costa, Elena; Bitetto, Davide; Fornasiere, Ezio; Fumolo, Elisa; Ferrarese, Alberto; Toniutto, Pierluigi","year":2025,"journal":"Journal of clinical medicine, 14(13)","doi":"10.3390/jcm14134619","pmid":"40648992","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11058","title":"Estrogens impair hypophagia and hypothalamic cell activation induced by vasoactive intestinal peptide, but not by pituitary adenylate cyclase-activating polypeptide.","authors":"Garnica-Siqueira, Marcela Cristina; Martins, Andressa Busetti; Monteiro, Érica Cristina Alves Munhoz; Oliveira, Maria Heloisa Bernardes de; Baratto, Carolina Dos Reis; Tsutsui, Fabiano Takeo Komay; Oliveira, Lucas Leonardo França de; Stopa, Larissa Rugila Dos Santos; Souza, Camila Franciele de; Wunderlich, Ana Luiza Machado; Zaia, Dimas Augusto Morozin; Leite, Cristiane Mota; Zaia, Cássia Thaïs Bussamra Vieira; Uchoa, Ernane Torres","year":2025,"journal":"Peptides, 183, 171325","doi":"10.1016/j.peptides.2024.171325","pmid":"39617208","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Estradiol-treated ovariectomized rats showed reduced VPAC2 receptor mRNA in the PVN. VIP-induced appetite suppression was completely blocked by estradiol, while PACAP still reduced food intake in both estrogen-treated and untreated groups. VIP-induced cell activation in the ARC and PVN was blocked by estradiol, but PACAP still activated ARC cells in both groups (PVN activation was blocked only in estrogen-treated rats). VIP increased plasma glucose in both groups; PACAP increased glucose only without estrogen. VIP decreased free fatty acids only with estrogen present.","whyItMatters":"Menopause is associated with weight gain and changes in appetite regulation, partly due to declining estrogen. Understanding how estrogen interacts with specific appetite-regulating peptides helps explain these changes and could guide the development of targeted therapies. The finding that PACAP maintains its appetite-suppressing effect regardless of estrogen status makes it a potentially more reliable therapeutic target for postmenopausal weight management.","specificNumbers":"","methodology":"Female Wistar rats underwent ovariectomy and intracerebroventricular cannulation surgery. They received daily subcutaneous injections of either corn oil (vehicle) or 10 μg estradiol cypionate. VIP or PACAP was administered by intracerebroventricular microinjection. Researchers measured food intake, plasma glucose and free fatty acids, VPAC2 and PAC1 receptor mRNA expression, and hypothalamic cell activation (c-Fos) in the ARC and PVN nuclei.","limitations":"This is a rat study using surgical menopause (ovariectomy), which is more abrupt than natural menopause in humans. The neuropeptides were delivered directly into the brain, which doesn't reflect physiological signaling. Only one dose of estradiol was tested. The study examined acute effects; chronic peptide exposure may produce different results. The small sample sizes typical of such studies limit statistical power."},{"rthcId":"RPEP-11059","title":"Production of Protein Hydrolysates with Antioxidant and Antihypertensive Activity from Edible Larvae of Aegiale hesperiaris and Comadia redtenbacheri.","authors":"Garrido-Ortiz, Eduardo R; Morales-Camacho, Jocksan I","year":2025,"journal":"Foods (Basel, Switzerland), 14(12)","doi":"10.3390/foods14122124","pmid":"40565733","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Sequential hydrolysis with pepsin and trypsin (PTH) produced the most bioactive peptides, showing ABTS radical inhibition above 90% and DPPH radical scavenging of 75–85%. ACE inhibitory activity was exceptional: red worm hydrolysate (RWPH) achieved an IC50 of 0.017 μg/mL — about sixfold more potent than enalapril (IC50 = 0.11 μg/mL). White worm hydrolysate (WWPH) had an IC50 of 0.35 μg/mL.\n\nSDS-PAGE analysis revealed the active peptides were low molecular weight (<10 kDa, primarily 5–9 kDa). Red worm peptides showed low Hill coefficients, indicating gradual and sustained interaction with the ACE enzyme rather than an abrupt on-off binding — a pharmacologically favorable property.","whyItMatters":"Edible insects are increasingly recognized as a sustainable protein source that could help feed a growing global population. Finding that these traditional food sources also contain peptides with pharmaceutical-level bioactivity adds significant value. If these findings translate to human consumption, edible insect products could serve dual roles as nutrition and functional food for cardiovascular health — particularly relevant in populations where access to prescription blood pressure medications is limited.","specificNumbers":"","methodology":"Proteins were extracted from two edible Mexican insect species (Aegiale hesperiaris and Comadia redtenbacheri) and hydrolyzed using either pepsin alone (PH) or pepsin followed by trypsin (PTH). Hydrolysates were characterized by SDS-PAGE for molecular weight distribution. Antioxidant activity was measured using ABTS and DPPH assays. ACE inhibitory activity was determined by IC50 values and Hill coefficient analysis. Results were compared against the pharmaceutical ACE inhibitor enalapril.","limitations":"All bioactivity testing was performed in vitro (test tube assays), not in living organisms or humans. The exceptional ACE inhibition IC50 values may not translate to blood pressure-lowering effects after oral consumption, as the peptides would need to survive digestion and reach the bloodstream intact. The comparison with enalapril is based on enzyme inhibition assays, not clinical blood pressure outcomes — enalapril has decades of proven clinical efficacy. Whether regular consumption of these insects would provide meaningful cardiovascular benefits is entirely unknown."},{"rthcId":"RPEP-11060","title":"Glucagon-like Peptide 1 Receptor Agonists and Risk of Pulmonary Hypertension.","authors":"Garry, Jonah D; Kundu, Suman; Alcorn, Chuck; Eden, Svetlana; Smith, Emily; Greevy, Robert; Tindle, Hilary A; Freiberg, Matthew S; Brittain, Evan L","year":2025,"journal":"medRxiv : the preprint server for health sciences","doi":"10.1101/2025.09.18.25336100","pmid":"41001493","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11061","title":"Clinical Outcomes of Glucagon-Like Peptide-1 Receptor Agonist (GLP-1 RA) and Glucagon-Like Peptide-1/Glucose-Dependent Insulinotropic Polypeptide Receptor Agonist (GLP-1/GIP RA) Exposures Presenting to the Emergency Department.","authors":"Gartner, Hayley T; Simmons, Reeves E; Wan, Herbert Z; Sollee, Dawn R; Sheikh, Sophia","year":2025,"journal":"The Annals of pharmacotherapy, 59(12), 1057-1068","doi":"10.1177/10600280251334642","pmid":"40269635","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11062","title":"Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity.","authors":"Garvey, W Timothy; Blüher, Matthias; Osorto Contreras, Cynthia Karenina; Davies, Melanie J; Winning Lehmann, Eva; Pietiläinen, Kirsi H; Rubino, Domenica; Sbraccia, Paolo; Wadden, Thomas; Zeuthen, Niels; Wilding, John P H","year":2025,"journal":"The New England journal of medicine, 393(7), 635-647","doi":"10.1056/NEJMoa2502081","pmid":"40544433","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11063","title":"Genetically Modified Mesenchymal Stromal/Stem Cells as a Delivery Platform for SE-33, a Cathelicidin LL-37 Analogue: Preclinical Pharmacokinetics and Tissue Distribution in C57BL/6 Mice.","authors":"Gasanov, Vagif Ali Oglu; Kashirskikh, Dmitry Alexandrovich; Khotina, Victoria Alexandrovna; Lee, Arthur Anatolievich; Nikitochkina, Sofya Yurievna; Kuzmina, Daria Mikhailovna; Mukhina, Irina Vasilievna; Vorotelyak, Ekaterina Andreevna; Vasiliev, Andrey Valentinovich","year":2025,"journal":"Antibiotics (Basel, Switzerland), 14(5)","doi":"10.3390/antibiotics14050429","pmid":"40426496","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11064","title":"Changes in weight and glycemic control following obesity treatment with semaglutide or tirzepatide by discontinuation status.","authors":"Gasoyan, Hamlet; Butsch, W Scott; Schulte, Rebecca; Casacchia, Nicholas J; Le, Phuc; Boyer, Christopher B; Griebeler, Marcio L; Burguera, Bartolome; Rothberg, Michael B","year":2025,"journal":"Obesity (Silver Spring, Md.), 33(9), 1657-1667","doi":"10.1002/oby.24331","pmid":"40491239","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 7,881 patients (6,109 on semaglutide, 1,772 on tirzepatide), the mean percentage weight reduction at 1 year was 8.7% overall. Results varied dramatically by discontinuation status:\n\n- Non-discontinuation: 11.9% weight loss (SD 9.2%)\n- Late discontinuation (3-12 months): 6.8% weight loss (SD 9.1%)\n- Early discontinuation (within 3 months): 3.6% weight loss (SD 8.1%)\n\nAll differences were statistically significant (p < 0.001). For patients with prediabetes, glycated hemoglobin (HbA1c) reductions followed the same pattern: 0.4% for continuers, 0.2% for late discontinuers, and 0.1% for early discontinuers. Notably, 80.8% of patients had low maintenance dosages, suggesting most patients were not on the maximum approved doses used in clinical trials.","whyItMatters":"Clinical trials of semaglutide and tirzepatide showed impressive weight loss (15-20%+), driving massive public interest. But this real-world study reveals a significant efficacy-effectiveness gap — actual results are lower because many patients stop treatment early or never reach maximum doses. This has major implications for patients, prescribers, insurers, and policymakers setting expectations for GLP-1 obesity medications.","specificNumbers":"","methodology":"Retrospective cohort study using electronic health records from a large health system in Ohio and Florida. Adults with overweight or obesity (without type 2 diabetes) who started injectable semaglutide or tirzepatide between 2021 and 2023 were followed through December 2024. Discontinuation was defined as a >90-day gap between medication supply exhaustion and next dispense, categorized as early (within 3 months) or late (3-12 months).","limitations":"Retrospective design using EHR data, which may not capture medications obtained outside the health system or reasons for discontinuation. The study could not account for lifestyle changes, diet, or exercise. Patients without type 2 diabetes were included, so results may not generalize to diabetic populations. The study period overlapped with significant supply shortages for these medications, which may have contributed to discontinuation rates."},{"rthcId":"RPEP-11065","title":"Macrovascular and microvascular outcomes of metabolic surgery versus GLP-1 receptor agonists in patients with diabetes and obesity.","authors":"Gasoyan, Hamlet; Alavi, Mohammad Hesam; Zajichek, Alexander; Casacchia, Nicholas J; Al Jabri, Abdullah; Bena, James; Feng, Xiaoxi; Wilson, Rickesha; Corcelles, Ricard; Butsch, W Scott; Singh, Rishi P; Das, Nikhil; Jeong, Hejin; Mentias, Amgad; Tang, W H Wilson; Burguera, Bartolome; Rosenthal, Raul J; Nissen, Steven E; Rothberg, Michael B; Aminian, Ali","year":2025,"journal":"Nature medicine, 31(10), 3341-3349","doi":"10.1038/s41591-025-03893-3","pmid":"40957960","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11066","title":"Reasons for Discontinuation of Obesity Pharmacotherapy With Semaglutide or Tirzepatide in Clinical Practice.","authors":"Gasoyan, Hamlet; Butsch, W Scott; Casacchia, Nicholas J; Schulte, Rebecca; Criswell, Victoria; Fox, Jacqueline; Renner, Holly; Le, Phuc; Alpert, Jordan; Rothberg, Michael B","year":2025,"journal":"Obesity (Silver Spring, Md.), 33(12), 2296-2303","doi":"10.1002/oby.70058","pmid":"41039650","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11067","title":"The Effects of GLP-1 Agonists on Musculoskeletal Health and Orthopedic Care.","authors":"Gatto, Andrew; Liu, Kevin; Milan, Nesa; Wong, Stephanie","year":2025,"journal":"Current reviews in musculoskeletal medicine, 18(10), 469-480","doi":"10.1007/s12178-025-09978-3","pmid":"40372699","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11068","title":"From the SELECT study to SOUL: different administration methods of semaglutide but same efficacy?","authors":"Gatto, Laura; Biccirè, Flavio Giuseppe; Lentini, Antonio Emanuele; Scalia, Lorenzo; Prati, Francesco","year":2025,"journal":"European heart journal supplements : journal of the European Society of Cardiology, 27(Suppl 3), iii98-iii101","doi":"10.1093/eurheartjsupp/suaf024","pmid":"40248301","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11069","title":"Patterns of prescription and discontinuation of glucagon-like peptide-1 receptor agonists among patients with irritable bowel syndrome.","authors":"Gautam, Misha; Goel, Utkarsh; Bader, Abbas; Azim, Samiya; Hassan, Noor; Sadeddin, Esmat; Clarkston, Wendell; Ghoz, Hassan","year":2025,"journal":"Annals of gastroenterology, 38(4), 420-427","doi":"10.20524/aog.2025.0971","pmid":"40697433","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11070","title":"Antibacterial efficacy of a peptide co-assembled hydrogel matrix for wound care.","authors":"Gavel, Pramod K; Rit, Tanmay; Bagde, Pranit Hemant; Parmar, Hamendra S; Jha, Hem Chandra; Das, Apurba K","year":2025,"journal":"International journal of biological macromolecules, 331(Pt 2), 148388","doi":"10.1016/j.ijbiomac.2025.148388","pmid":"41115552","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"An Amoc-capped dipeptide co-assembled with β-cyclodextrin under physiological conditions (pH 7.4, 37°C) to form a self-supporting hydrogel with entangled nanofibrillar networks.\n\nThe hydrogel demonstrated:\n- Inherent antibacterial activity against Gram-positive bacteria Bacillus subtilis and Staphylococcus aureus\n- Mechanism of killing: aggregation-induced membrane permeabilization and rupture (confirmed by SEM)\n- Shear-thinning behavior enabling easy application\n- Biocompatibility with HEK293 and AGS cell lines\n- In vivo wound healing confirmed by digital photography and histopathological analysis\n- Anti-inflammatory activity via reduction of nitrite levels during healing","whyItMatters":"Chronic wounds and antibiotic-resistant infections are growing healthcare challenges. A wound dressing that inherently kills bacteria without traditional antibiotics — while also promoting healing and reducing inflammation — could help address both problems simultaneously, especially as antibiotic resistance continues to rise.","specificNumbers":"","methodology":"The hydrogel was prepared by co-assembling Amoc-capped dipeptide with β-cyclodextrin at physiological pH and temperature. Characterization included electron microscopy (nanostructure), rheology (mechanical properties), and shear-thinning tests. Antibacterial activity was tested against B. subtilis and S. aureus with SEM imaging of bacterial damage. Biocompatibility was assessed with HEK293 and AGS cell lines. In vivo wound healing was evaluated in mice through photographic monitoring and histopathological analysis.","limitations":"Only Gram-positive bacteria were tested; activity against Gram-negative bacteria (which cause many wound infections) was not reported. The mouse wound model may not fully represent human wound healing, particularly for chronic or diabetic wounds. Long-term stability and shelf life of the hydrogel were not assessed. Manufacturing scalability was not addressed."},{"rthcId":"RPEP-11071","title":"Differences in GLP-1 RA medication adherence across place-based variables in patients with diabetes living in Wisconsin.","authors":"Gavin, Kara L; Amjad, Rabia; Makris, Vaia; Neuner, Joan M","year":2025,"journal":"Journal of managed care & specialty pharmacy, 31(12), 1311-1319","doi":"10.18553/jmcp.2025.31.12.1311","pmid":"41296314","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11072","title":"Antimicrobial Peptides Versus Antibiotics in Farm Animal Production.","authors":"Gavrilov, Boris; Davidova, Slavena; Generalova, Anastasiia; Gergova, Alexandra; Satchanska, Galina","year":2025,"journal":"Antibiotics (Basel, Switzerland), 14(11)","doi":"10.3390/antibiotics14111108","pmid":"41301603","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11073","title":"Short but promising - how nature modulates the antimicrobial activity of proline-rich fragment of salivary MUC-7.","authors":"Gawłowski, Jakub; Ślusarczyk, Anna; Szarszoń, Klaudia; Zobi, Fabio; Janek, Tomasz; Wątły, Joanna","year":2025,"journal":"Dalton transactions (Cambridge, England : 2003), 54(35), 13257-13270","doi":"10.1039/d5dt01418b","pmid":"40824297","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The shortest proteolytic fragment (L3, sequence HPDK) of the MUC7-derived peptide formed the most thermodynamically stable complexes with both Cu(II) and Zn(II) ions and exhibited the strongest antimicrobial activity among all tested sequences. This activity was pH-dependent, consistent with a \"nutritional immunity\" mechanism where the peptide starves microbes of essential metal ions.\n\nThe finding that natural enzymatic cleavage enhances rather than destroys the peptide's function challenges the assumption that proteolysis is purely degradative, suggesting an evolutionary advantage to peptide fragmentation.","whyItMatters":"Antimicrobial resistance is a growing global crisis, and peptide-based antimicrobials represent a promising alternative to conventional antibiotics. This study reveals that nature already has a sophisticated system for optimizing antimicrobial peptides through enzymatic processing — insights that could guide the design of new metal-coordinating antimicrobial drugs.","specificNumbers":"","methodology":"The researchers synthesized three peptides — the parent sequence (L1) and two fragments (L2, L3) produced by trypsin cleavage. They used multiple analytical techniques including potentiometry, UV-vis spectroscopy, circular dichroism, electron paramagnetic resonance, mass spectrometry, and computational modeling to characterize how each peptide binds copper and zinc. Antimicrobial activity was tested in standard microbial assays.","limitations":"This is an in vitro study using purified peptides and controlled conditions, so how these fragments behave in the complex environment of the oral cavity remains unknown. The specific microbial strains tested and the concentrations used may not fully represent real-world oral infections. No animal or human studies were conducted to validate in vivo efficacy."},{"rthcId":"RPEP-11074","title":"Genomic configuration of Bacillus subtilis (NMB01) unveils its antiviral activity against Orthotospovirus arachinecrosis infecting tomato.","authors":"Gayathri, M; Sharanya, R; Renukadevi, P; Malathi, Varagur Ganesan; Ghosh, Amalendu; Nallusamy, Saranya; Varanavasiappan, S; Nakkeeran, S; Alkahtani, Saad","year":2025,"journal":"Frontiers in plant science, 16, 1517157","doi":"10.3389/fpls.2025.1517157","pmid":"40104030","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11075","title":"Human Substance P Interactions with G Protein-Coupled Receptor NK1R Observed by NMR in Solution.","authors":"Ge, Haoyi; Yang, Lingyun; Chen, Changran; Xu, Yuxin; Liu, Dongsheng; Wüthrich, Kurt","year":2025,"journal":"Journal of the American Chemical Society, 147(48), 44114-44122","doi":"10.1021/jacs.5c12553","pmid":"41264783","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Using 19F-NMR spectroscopy with fluorine probes placed at five positions along Substance P (positions 0, 3, 5, 7, and 8), researchers found that the C-terminal hexapeptide segment is rigidly anchored within NK1R's orthosteric binding pocket, while the N-terminal pentapeptide segment remains flexible and solvent-exposed when bound. Critically, transient interactions between the side chains of Lys3 and Gln5 in Substance P with sites on NK1R significantly impact the peptide's functional potency, as confirmed by cAMP function assays. This reveals that dynamic, short-lived molecular contacts — invisible to static structural methods like cryo-EM — play important roles in peptide-receptor signaling.","whyItMatters":"NK1R antagonists are already used clinically for treating nausea (e.g., aprepitant for chemotherapy-induced nausea). Understanding exactly how Substance P binds and activates NK1R at the molecular level could lead to better-designed drugs that more precisely block this interaction, potentially improving treatments for pain, nausea, inflammation, and neurological disorders.","specificNumbers":"","methodology":"The researchers used 19F-NMR spectroscopy, introducing a fluorinated amino acid probe (mtfF) at five positions in Substance P. They observed the peptide in three states: free in solution, bound to lipid micelles, and bound to micelle-solubilized NK1R. They measured exchange rates between all states and complemented the NMR data with cyclic AMP functional assays to assess how specific interactions affected receptor activation.","limitations":"The study was conducted in vitro using micelle-solubilized receptor rather than a native cell membrane environment. The NMR approach required introducing modified amino acids into the peptide, which could subtly alter binding behavior despite functional validation. Results are specific to the NK1R-Substance P system and may not directly generalize to other peptide-GPCR pairs."},{"rthcId":"RPEP-11076","title":"GPR40 signaling in agouti-related peptide neurons mediates fat preference.","authors":"Ge, Yueping; Zhan, Huidong; Wu, Shanshan; Wang, Jing; Xu, Yang; Liang, Yixiao; Peng, Li; Gao, Ling; Zhao, Jiajun; He, Zhao","year":2025,"journal":"Life sciences, 373, 123677","doi":"10.1016/j.lfs.2025.123677","pmid":"40320138","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GPR40 in hypothalamic AgRP neurons is a novel pathway regulating dietary fat preference. AgRP-specific Gpr40 knockout mice showed reduced fat preference and increased carbohydrate intake. This was not related to behavioral abnormalities. After starvation, knockout mice had diminished metabolic state, increased AgRP neuronal activity, and elevated AgRP and NPY peptide levels, yet reduced fat intake. Inhibiting AgRP neuronal activity in knockout mice rescued fat preference, confirming that GPR40's effects are mediated through neuronal activity modulation. This pathway was specific to AgRP neurons — POMC neurons were not involved.","whyItMatters":"Understanding why the brain drives us to prefer high-fat foods is crucial for tackling obesity. This study identifies GPR40 in AgRP neurons as a specific molecular switch for fat preference — separate from general hunger. This could lead to targeted therapies that reduce fat cravings without affecting overall appetite or causing mood disorders, offering a more precise approach to obesity treatment than current medications.","specificNumbers":"","methodology":"Researchers generated AgRP neuron-specific Gpr40 knockout mice using genetic engineering. They conducted behavioral tests to assess dietary preferences between fat and carbohydrates, along with tests for anxiety, depression, and memory. Metabolic analyses were performed after starvation. AgRP neuronal activity was measured, and expression levels of AgRP and NPY peptides were quantified. A rescue experiment inhibited AgRP neurons to confirm the mechanism.","limitations":"This is a mouse study, and dietary preference mechanisms may differ in humans. The knockout was specific to AgRP neurons, which doesn't capture GPR40's potential roles in other brain regions. The study focused on a two-choice paradigm (fat vs. carbohydrate) and did not assess more complex dietary scenarios. Long-term effects of altered fat preference on body weight were not fully characterized."},{"rthcId":"RPEP-11077","title":"Co-delivery of azithromycin and nisin through liposomes for skin infection to reduce antimicrobial drug resistance.","authors":"Gelen-Gungor, Dilek; Nigiz, Şeyma; Özkul, Ceren; Eroğlu, Hakan; Nemutlu, Emirhan; Ulubayram, Kezban; Mao, Yong; Michniak-Kohn, Bozena; Eroğlu, İpek","year":2025,"journal":"International journal of pharmaceutics, 679, 125764","doi":"10.1016/j.ijpharm.2025.125764","pmid":"40414326","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11078","title":"Advanced microbiome therapeutics for oral delivery of peptides and proteins: Advances, challenges, and opportunities.","authors":"Gelli, Hitesh P; Vazquez-Uribe, Ruben; Buckley, Stephen T; Andersen, Jan Terje; Alexander Sommer, Morten Otto","year":2025,"journal":"Advanced drug delivery reviews, 222, 115603","doi":"10.1016/j.addr.2025.115603","pmid":"40349728","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11079","title":"Enhancing intestinal absorption of a macromolecule through engineered probiotic yeast in the murine gastrointestinal tract.","authors":"Gelli, Hitesh P; Hedin, Karl Alex; Laursen, Martin F; Uribe, Ruben-Vazquez; Sommer, Morten Otto Alexander","year":2025,"journal":"Trends in biotechnology, 43(3), 715-731","doi":"10.1016/j.tibtech.2024.10.019","pmid":"39658447","tags":[],"studyType":"in-vivo","evidenceStrength":"moderate","keyFinding":"Researchers engineered the probiotic yeast Saccharomyces boulardii to produce cell-penetrating peptides (CPPs) directly inside the gut, enhancing intestinal absorption of large molecules. Four different CPPs were integrated into the yeast's chromosome: RRL helix, Shuffle, Penetramax, and PN159. In cell culture (Caco-2 model), three of the four CPP-producing strains increased intestinal permeability without causing permanent damage to the gut lining.\n\nIn live mice, the PN159-producing yeast strain significantly increased FITC-dextran (a model macromolecule) absorption into the bloodstream over 10 days — without causing gut inflammation. This is the first demonstration that an engineered microorganism can modulate host intestinal permeability to improve macromolecule absorption.","whyItMatters":"The biggest barrier to oral peptide drugs is that they get destroyed in the stomach or can't cross the intestinal wall. This study proposes an elegant solution: a living probiotic yeast that colonizes your gut and continuously produces peptides that temporarily open the intestinal barrier, allowing therapeutic molecules to pass through. If this approach works for actual peptide drugs (not just model molecules), it could eliminate the need for injections for many peptide therapies.","specificNumbers":"4 CPPs tested · 3/4 effective in vitro · Sb PN159 effective in vivo · 10-day mouse study · No inflammation · First-in-class demonstration","methodology":"Cell-penetrating peptide genes were chromosomally integrated into S. boulardii probiotic yeast. In vitro testing used Caco-2 intestinal cell monolayers to assess permeability changes and cell damage. In vivo experiments administered the engineered yeast to mice for 10 days, then measured FITC-dextran translocation from gut to bloodstream as a proxy for macromolecule absorption. Inflammation markers were assessed to confirm safety.","limitations":"The study used FITC-dextran as a model macromolecule — not an actual peptide drug — so therapeutic absorption remains unproven. Mouse gut physiology differs from human gut. Increased intestinal permeability could theoretically allow unwanted molecules (bacteria, toxins) to enter the bloodstream too, raising long-term safety questions. The 10-day study duration doesn't address chronic use effects. Regulatory pathway for a genetically engineered probiotic would be complex."},{"rthcId":"RPEP-11080","title":"Charge regulation in peptide self-assembly and hydrogelation.","authors":"Gentile, Luigi; Frohm, Birgitta; Malmendal, Anders; Åkerfeldt, Karin S; Olsson, Ulf; Linse, Sara","year":2025,"journal":"Journal of colloid and interface science, 700(Pt 3), 138615","doi":"10.1016/j.jcis.2025.138615","pmid":"40773884","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A 13-amino-acid peptide (KD) derived from human semenogelin I self-assembled into a pH-responsive hydrogel whose mechanical properties were tuned by histidine protonation state changes. As pH drifted during assembly, histidine's charge changed, driving the peptide from solution into β-sheet fibrils that formed a hydrogel network.\n\nCryo-TEM revealed two distinct nanostructures — fibrils and twisted curly nanostructures — that evolved over time. The elastic modulus increased substantially with pH shift, and under buffered conditions the peptide formed hydrogels within the experimental dead time (near-instantaneously). The mechanism centers on charge regulation of a single histidine residue controlling the entire self-assembly process.","whyItMatters":"pH-responsive materials are highly sought after in drug delivery and tissue engineering because the body has many pH gradients (stomach acid, tumor microenvironments, wound sites). This study reveals how a single amino acid's charge state can act as a molecular switch, controlling whether a peptide is dissolved or gelled. This mechanistic insight enables rational design of peptide hydrogels that respond to specific pH environments — useful for targeted drug release, wound healing, or injectable scaffolds that gel upon reaching physiological conditions.","specificNumbers":"13-amino-acid peptide · pH-driven gelation · Histidine pKa modulation · 2 distinct nanostructures · Elastic modulus increased with pH · Near-instantaneous gelation under buffer","methodology":"Researchers studied the self-assembly of the KD peptide using time-resolved NMR spectroscopy to track molecular-level changes, cryo-TEM for nanostructural imaging, pH measurements during assembly, and oscillatory and stationary rheology to measure mechanical properties. Experiments were conducted under varying pH and buffer conditions to characterize the pH-responsiveness.","limitations":"This is a fundamental biophysics study — no biological applications were tested. The peptide is derived from human semenogelin I, but its relevance to the protein's natural function is not discussed. Biocompatibility, cell viability, and drug release capability were not assessed. The study focused on a single peptide sequence; the generalizability of the histidine charge regulation mechanism to other peptides is assumed but not demonstrated."},{"rthcId":"RPEP-11081","title":"Obstructive Sleep Apnea and Type 2 Diabetes: An Update.","authors":"Gentile, Sandro; Monda, Vincenzo Maria; Guarino, Giuseppina; Satta, Ersilia; Chiarello, Maria; Caccavale, Giuseppe; Mattera, Edi; Marfella, Raffaele; Strollo, Felice","year":2025,"journal":"Journal of clinical medicine, 14(15)","doi":"10.3390/jcm14155574","pmid":"40807193","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11082","title":"Effect of supplementation with type 1 and type 3 collagen peptide and type 2 hydrolyzed collagen on osteoarthritis-related pain, quality of life, and physical function: A double-blind, randomized, placebo-controlled study.","authors":"Genç, Ahmet Serhat; Yılmaz, Ali Kerim; Anıl, Berna; Korkmaz Salkılıç, Esra; Akdemir, Enes; Sancaklı, Aykut; Mor, Ahmet; Ermiş, Egemen; Baraz, Lale Saka; Güzel, Nizamettin; Kehribar, Lokman","year":2025,"journal":"Joint diseases and related surgery, 36(1), 85-96","doi":"10.52312/jdrs.2025.1965","pmid":"39719905","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11083","title":"The effect of supplementation with type I and type III collagen peptide and type II hydrolyzed collagen on pain, quality of life and physical function in patients with meniscopathy: a randomized, double-blind, placebo-controlled study.","authors":"Genç, Ahmet Serhat; Yılmaz, Ali Kerim; Anıl, Berna; Korkmaz Salkılıç, Esra; Akdemir, Enes; Güzel, Berna; Mor, Ahmet; Yarar, Hacı Ahmet; Güzel, Nizamettin; Kehribar, Lokman","year":2025,"journal":"BMC musculoskeletal disorders, 26(1), 17","doi":"10.1186/s12891-024-08244-w","pmid":"39755603","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11084","title":"Migraine in women: a review.","authors":"Ghadiri-Sani, M","year":2025,"journal":"Current opinion in neurology, 38(3), 271-276","doi":"10.1097/WCO.0000000000001372","pmid":"40265504","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11085","title":"Unveiling Tirzepatide's Therapeutic Spectrum: A Dual GIP/GLP-1 Agonist Targeting Metabolic, Neurological, and Cardiovascular Health.","authors":"Ghaleb, Joya; Khouzami, Katy Kaleen; Nassif, Nicolas; Attieh, Philippe; Ajlani, Mohammad Feras Al; Sleiman, Jana Bou; Khalouf, Ali; Harb, Frederic; Azar, Sami; Kannan, Amjad; Ghadieh, Hilda E","year":2025,"journal":"International journal of endocrinology, 2025, 2876156","doi":"10.1155/ije/2876156","pmid":"41069980","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tirzepatide's dual GIP/GLP-1 receptor agonism addresses multiple pathophysiological pathways simultaneously: insulin resistance, chronic inflammation, and oxidative stress. Clinical and preclinical data support therapeutic potential across type 2 diabetes, obesity, cardiovascular health, metabolic-associated fatty liver disease (MAFLD), chronic kidney disease (CKD), and neurological disorders including Alzheimer's and Parkinson's diseases.\n\nThe review synthesizes evidence showing tirzepatide's efficacy in Asian populations specifically, addressing a gap in the literature since this demographic is frequently underrepresented in global clinical trials despite high rates of metabolic disease.","whyItMatters":"Tirzepatide may be the most versatile peptide drug in modern medicine. By showing benefit across diabetes, obesity, heart disease, liver disease, kidney disease, and potentially brain disorders, it challenges the traditional one-drug-one-disease model. Understanding its full therapeutic spectrum could fundamentally change how clinicians approach patients with multiple chronic conditions, offering a single treatment that addresses several at once.","specificNumbers":"","methodology":"This is a comprehensive narrative review synthesizing clinical trial data, preclinical studies, and mechanistic research on tirzepatide's effects across metabolic, cardiovascular, hepatic, renal, and neurological conditions. Special attention was given to evidence from Asian population studies.","limitations":"As a narrative review, no new data are presented. Much of the evidence for non-diabetic applications comes from preclinical studies or secondary endpoints of diabetes trials rather than dedicated randomized trials for each condition. Long-term safety data across all proposed indications are limited. The neurological benefits are primarily based on preclinical models, not human clinical data."},{"rthcId":"RPEP-11086","title":"The Use of Semaglutide in Patients Undergoing Lumbar Fusion Does not Increase 90-Day Medical or 1-Year Implant Complications.","authors":"Ghali, Abdullah; Lawand, Jad; Mitchell, Parker; Momtaz, David; Ghilzai, Umar; Phan, Eileen; Alawa, Jude; Deveza, Lorenzo","year":2025,"journal":"Clinical spine surgery, 38(10), E579-E584","doi":"10.1097/BSD.0000000000001800","pmid":"40096579","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11087","title":"Association between Insulin-Like Growth Factor Binding Protein-7 and Heart Failure.","authors":"Ghasempour, Parisa; Khanmohammadi, Shaghayegh; Rezaei, Nima","year":2025,"journal":"Current medicinal chemistry, 32(42), 9636-9652","doi":"10.2174/0109298673346933241223063559","pmid":"39950473","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11088","title":"Effects of amino acids methionine, lysine, and taurine on feed intake and mRNA expression of appetite-related neuropeptides in layer-type chicks.","authors":"Ghashghaei, Elham; Wang, Minghui; Mijiyawa, Ahmed; Lin, Hai","year":2025,"journal":"Poultry science, 104(10), 105586","doi":"10.1016/j.psj.2025.105586","pmid":"40743628","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11089","title":"Anti-Inflammatory Peptides as Promising Therapeutics Agent Against Inflammatory Bowel Diseases: A Systematic Review.","authors":"Ghazvini, Kiarash; Taghiabadi, Zahra; Karimi, Mohammad Ali; Hosseini Bafghi, Mahdi; Paryan, Mahdiesadat; Amirfakhrian, Razieh","year":2025,"journal":"JGH open : an open access journal of gastroenterology and hepatology, 9(7), e70212","doi":"10.1002/jgh3.70212","pmid":"40589771","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11090","title":"GLP-1 Receptor Agonists as Emerging Modulators of Inflammation and Angiogenesis in Chronic Cutaneous Wound Healing.","authors":"Ghebrehiwet-Kuflom, Johanna; Mehta, Alisha; Lim, Pallas; Dahle, Sara; Isseroff, R Rivkah","year":2025,"journal":"The Journal of investigative dermatology, 145(12), 2981-2988","doi":"10.1016/j.jid.2025.08.045","pmid":"41081666","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11091","title":"From simulation to immunization: efficient non-viral delivery of HIV-1 Nefmut-Tat DNA construct using CM18-TAT11 cell penetrating peptide.","authors":"Gheydi, Mostafa; Bolhassani, Azam; Negahdari, Babak; Pordanjani, Parisa Moradi; Malekshahi, Ziba Veisi; Agi, Elnaz","year":2025,"journal":"International journal of pharmaceutics, 686, 126334","doi":"10.1016/j.ijpharm.2025.126334","pmid":"41177315","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11092","title":"GLP1 receptor agonists and SGLT2 inhibitors for the prevention or delay of type 2 diabetes mellitus onset: a systematic review and meta-analysis.","authors":"Ghobar, Farah; Tarhini, Ali; Osman, Zeinab; Sbeih, Sergio; Ghayda, Ralph Abou; Matar, Patena; Haddad, Gaelle; Kanaan, Amjad; Eid, Assaad; Azar, Sami; Ghadieh, Hilda E; Harb, Frederic","year":2025,"journal":"Frontiers in endocrinology, 16, 1627909","doi":"10.3389/fendo.2025.1627909","pmid":"41210503","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11093","title":"Boronic Acid-Linked Apo-Zinc Finger Protein for Ubiquitin Delivery in Live Cells.","authors":"Ghosh, Pritam; Seitz, Oliver","year":2025,"journal":"Chembiochem : a European journal of chemical biology, 26(7), e202401040","doi":"10.1002/cbic.202401040","pmid":"39950407","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11094","title":"Transcriptional diversification in a human-adapting zoonotic pathogen drives niche-specific evolution.","authors":"Ghosh, Soma; Wu, Chao-Jung; Moller, Abraham G; Launay, Adrien; Hall, Laina N; Hansen, Bryan T; Fischer, Elizabeth R; Youn, Jung-Ho; Khil, Pavel P; Dekker, John P","year":2025,"journal":"Nature communications, 16(1), 2067","doi":"10.1038/s41467-025-57331-6","pmid":"40021638","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11095","title":"Effect of liraglutide biosimilar vs. reference liraglutide on weight reduction in T2DM patients with obesity: post hoc analysis of phase III trial.","authors":"Ghosh, Sujoy; Sethi, Bipin; Kalra, Sanjay; Baruah, Manash P; Mane, Abhishek; Choudhari, Sanjay; Petare, Anup; Jadhav, Mayur; Patil, Saiprasad; Barkate, Hanmant","year":2025,"journal":"Cardiovascular diabetology. Endocrinology reports, 11(1), 6","doi":"10.1186/s40842-025-00219-7","pmid":"41013709","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 179 Indian patients with type 2 diabetes and obesity (mean BMI ~29.8 kg/m²), biosimilar liraglutide and reference liraglutide both produced significant weight loss over 24 weeks. The biosimilar group lost 5.5 ± 1.2 kg (7.3% body weight) while the reference group lost 7.1 ± 2.6 kg (8.9% body weight). Crucially, the difference between groups was not statistically significant (p = 0.71), confirming non-inferiority.\n\nGlycemic parameters also improved significantly in both arms: HbA1c (p = 0.89 between groups), fasting plasma glucose (p = 0.43), and postprandial glucose (p = 0.17) were all comparable at week 24, with no meaningful advantage for either formulation.","whyItMatters":"Liraglutide is an effective but expensive GLP-1 drug for diabetes and weight management. Biosimilars — essentially generic versions of biologic drugs — could dramatically lower costs and improve access, especially in countries like India where affordability is a major barrier to treatment. This study provides clinical evidence that the biosimilar version works just as well.","specificNumbers":"","methodology":"This was a post-hoc analysis of a Phase III clinical trial. Researchers selected 179 patients with type 2 diabetes and BMI above 25 kg/m² from the larger trial population. One group received biosimilar liraglutide and the other received reference (brand-name) liraglutide at doses up to 1.8 mg daily. The primary endpoint was mean change in body weight from baseline to week 24, with blood sugar measures as secondary endpoints.","limitations":"This was a post-hoc analysis, not a prospectively designed weight-loss trial, which weakens the strength of conclusions. The sample size of 179 is modest. The study was conducted only in Indian patients, so results may not generalize to other populations. The 24-week duration is relatively short for assessing weight management outcomes. The numerical weight loss difference (5.5 vs 7.1 kg) was not statistically significant but could be clinically meaningful."},{"rthcId":"RPEP-11096","title":"Advancing antisense oligonucleotide delivery through click chemistry based chemical conjugation with designed short non-cationic peptides for Duchenne muscular dystrophy.","authors":"Ghosh, Surojit; Arshi, Mohammad Umar; Ghosh, Satyajit; Jash, Moumita; Mukherjee, Nabanita; Jana, Aniket; Shastry, Arun; Karanth, Deepika; Nishad, Khushbu; Rana, Nirmal Kumar; Bhattacharyya, Sudipta; Ghosh, Surajit","year":2025,"journal":"Methods (San Diego, Calif.), 244, 92-107","doi":"10.1016/j.ymeth.2025.09.005","pmid":"40962198","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11097","title":"Characteristics and Treatment Patterns of People Without Type 2 Diabetes Diagnoses Who Use Tirzepatide in the United States.","authors":"Gibble, Theresa Hunter; Hankosky, Emily R; Meeks, Alexandra; Liao, Birong; Ward, Jennifer; Huang, Ahong; Chinthammit, Chanadda","year":2025,"journal":"Clinical therapeutics, 47(8), 572-580","doi":"10.1016/j.clinthera.2025.05.003","pmid":"40480878","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across two major US claims databases, 22,334 non-diabetic adults initiated tirzepatide between May 2021 and September 2023. Over 70% of users in both databases had at least one obesity-related complication (hypertension, dyslipidemia, or prediabetes). Most started at the 2.5 mg dose, with the most common doses at the sixth fill being 5 mg and 7.5 mg. Six-month persistence ranged from 60.6% to 75.7%, exceeding rates previously reported for GLP-1 receptor agonists. Among those who discontinued, 10-20% restarted during follow-up.","whyItMatters":"This study provides the first large-scale real-world snapshot of how tirzepatide is actually being used outside of diabetes. The high prevalence of obesity-related comorbidities suggests clinicians are prescribing it to patients with genuine cardiometabolic risk, not just for cosmetic weight loss. The strong persistence rates indicate patients are finding sustained benefit.","specificNumbers":"22,334 total users; >70% with obesity complications; 60.6-75.7% persistence at 6 months; 10.2-19.5% restart rate; most common doses at 6th fill: 5 mg and 7.5 mg","methodology":"Retrospective observational study using MarketScan Commercial and Optum Clinformatics claims databases. Included adults ≥18 with at least one tirzepatide claim, no type 2 diabetes diagnosis, and 12 months of continuous enrollment before first tirzepatide claim. Persistence and dosing patterns assessed at 6 months.","limitations":"Claims data cannot capture clinical outcomes like actual weight loss or cardiometabolic improvements. The study period preceded FDA approval of tirzepatide for weight management (as Zepbound), so some use may have been off-label. Insurance claims may not reflect total use including self-pay patients. No comparison group."},{"rthcId":"RPEP-11098","title":"Tirzepatide and health-related quality of life in adults with obesity or overweight: Results from the SURMOUNT-3 phase 3 randomized trial.","authors":"Gibble, Theresa Hunter; Cao, Dachuang; Forrester, Tammy; Fraseur Brumm, Julia; Chao, Ariana M","year":2025,"journal":"Diabetes, obesity & metabolism, 27(8), 4268-4279","doi":"10.1111/dom.16463","pmid":"40365662","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11099","title":"Tirzepatide Associated With Improved Health-Related Quality of Life in Adults With Obesity or Overweight in SURMOUNT-4.","authors":"Gibble, Theresa Hunter; Cao, Dachuang; Murphy, Madhumita; Jouravskaya, Irina; Liao, Birong; Bays, Harold Edward","year":2025,"journal":"Obesity (Silver Spring, Md.), 33(11), 2076-2092","doi":"10.1002/oby.70011","pmid":"40903801","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11100","title":"Type 2 diabetes mellitus - conventional therapies and future perspectives in innovative treatment.","authors":"Gieroba, Barbara; Kryska, Adrianna; Sroka-Bartnicka, Anna","year":2025,"journal":"Biochemistry and biophysics reports, 42, 102037","doi":"10.1016/j.bbrep.2025.102037","pmid":"40395625","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11101","title":"Roux-en-Y Gastric Bypass Improves Insulin Response and Secretion of GLP-1 and PYY in Response to Postprandial Acute Exercise.","authors":"Gil, Saulo; Murai, Igor Hisashi; Dantas, Wagner S; Merege-Filho, Carlos Alberto Abujabra; Leitão, Alice Erwig; Nicoletti, Carolina Ferreira; Lima, Alisson Padilha de; Benatti, Fabiana; Cleva, Roberto de; Santo, Marco Aurélio; Kirwan, John P; Gualano, Bruno; Roschel, Hamilton","year":2025,"journal":"Obesity surgery, 35(12), 4989-4999","doi":"10.1007/s11695-025-08327-0","pmid":"41238973","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Thirteen women with severe obesity (BMI 47.6 ± 5.6) underwent exercise sessions before and 3 months after Roux-en-Y gastric bypass:\n\nPre-surgery: No significant GLP-1 or PYY changes with post-meal exercise (all P>0.05)\n\nPost-surgery:\n- GLP-1 increased immediately (P=0.0180) and 30 min after exercise (P=0.0380); AUC rose from 2.3 to 14.5 pg/mL×min (P=0.0075) — a 6.3-fold increase\n- PYY increased immediately (P=0.0020) and 30 min after exercise (P=0.0360); AUC rose from 9.9 to 224.2 pg/mL×min (P=0.0004) — a 22.6-fold increase\n- Insulin AUC decreased (60.7 to 26.3 µU/mL×min; P=0.0457), indicating improved insulin sensitivity\n- PP and GIP AUC decreased post-surgery\n- Ghrelin levels and inflammatory markers were unchanged","whyItMatters":"This study reveals a key mechanism through which gastric bypass produces metabolic benefits: it restores the gut's ability to release appetite-suppressing and glucose-regulating peptides in response to exercise. The dramatic increases in GLP-1 and PYY after surgery help explain why patients eat less, have better blood sugar control, and lose weight. It also suggests that exercise and surgery work synergistically — combining both may produce greater metabolic benefits than either alone.","specificNumbers":"","methodology":"Thirteen women (age 37±7, BMI 47.6±5.6) completed an exercise session consisting of resistance training plus aerobic exercise in a postprandial state, both before and 3 months after Roux-en-Y gastric bypass surgery. Blood samples were collected at baseline, immediately after, and 30 minutes after exercise. Glucose, insulin, GLP-1, PYY, PP, GIP, ghrelin, and inflammatory markers were measured. Within-subject comparisons used pre- vs post-surgery exercise responses. AUC (area under the curve) was calculated for each hormone.","limitations":"Very small sample size (13 women) limits statistical power and generalizability. Only women were studied, so results may not apply to men. The 3-month post-surgery timepoint captures early changes — longer-term adaptations may differ. There was no non-surgical control group, so it's impossible to determine how much of the hormonal change is due to surgery versus weight loss itself. The exercise protocol combined resistance and aerobic training, making it difficult to determine which type of exercise drives the hormonal response."},{"rthcId":"RPEP-11102","title":"Epicardial Fat and Heart Failure in Type 2 Diabetes: Metabolism, Imaging and Novel Biomarkers-A Translational Perspective.","authors":"Gil-Millan, Pedro; Rives, José; Sánchez-Quesada, José Luis; Pérez, Antonio","year":2025,"journal":"Journal of clinical medicine, 14(23)","doi":"10.3390/jcm14238413","pmid":"41375727","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11103","title":"Optimization of aqueous remote loading of leuprolide in poly(lactic-co-glycolic acid) microspheres.","authors":"Giles, Morgan B; Walker, Jennifer; Schwendeman, Steven P","year":2025,"journal":"International journal of pharmaceutics, 685, 126206","doi":"10.1016/j.ijpharm.2025.126206","pmid":"40998225","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Aqueous remote loading of leuprolide into PLGA-COOH microspheres achieved ~9.8% drug loading with initial encapsulation efficiency of ~38%. Optimization revealed that high microsphere concentrations (180-240 mg/mL) strongly improved encapsulation efficiency, with quasi-equilibrium reached within 8 hours. Porosity (controlled by inner water phase volume, 0-350 μL) ranged from 38-60%, with minimal initial burst at low porosity. Drug loading and EE were not strongly affected above 50% porosity.\n\nA theoretical framework was derived showing that encapsulation efficiency depends on binding strength/capacity, polymer water content, and initial polymer concentration, while loading additionally depends on peptide/polymer mass ratio.","whyItMatters":"Long-acting injectable peptide formulations are critical for patient compliance — monthly injections are far more manageable than daily ones. This work improves the manufacturing process for loading peptide drugs into microspheres, potentially making production more efficient and enabling new long-acting formulations for other therapeutic peptides that are currently limited to short-acting injections.","specificNumbers":"","methodology":"Preformed 50/50 PLGA-COOH microspheres were loaded with leuprolide acetate in 0.1 M HEPES buffer (pH 7.4). Parameters optimized included microsphere concentration in loading solution, duration of loading, inner water phase volume, and porosity. In vitro release was assessed over 1 month. A quasi-equilibrium absorption model was developed to predict encapsulation efficiency and loading.","limitations":"The study focused on leuprolide as a model peptide; other peptides with different charge, size, or solubility may behave differently. Only in vitro release was assessed — in vivo pharmacokinetics were not studied. The theoretical model assumes quasi-equilibrium binding, which may not hold for all peptide-polymer combinations. Scale-up from laboratory conditions to commercial manufacturing was not addressed."},{"rthcId":"RPEP-11104","title":"Gut bacteria induce heterologous immune priming in Rhodnius prolixus encompassing both humoral and cellular immune responses.","authors":"Gilliland, Carissa A; Mugo-Kamiri, Loretta; Martin, Sara; Vogel, Kevin J","year":2025,"journal":"PLoS pathogens, 21(12), e1012947","doi":"10.1371/journal.ppat.1012947","pmid":"41325496","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11105","title":"Assessment of Exenatide Extended-Release for Maintenance of Diabetic Remission in Cats.","authors":"Gilor, Chen; Fleeman, Linda M; Hulsebosch, Sean E; Niessen, Stijn J M; Bjørnvad, Charlotte R; Pires, Jully; Hazuchova, Katarina; Mott, Jocelyn; O'Kell, Allison L; Gostelow, Ruth; Rudinsky, Adam J; Cook, Audrey K","year":2025,"journal":"Journal of veterinary internal medicine, 39(2), e70069","doi":"10.1111/jvim.70069","pmid":"40105430","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Exenatide extended-release did not significantly affect diabetic remission duration compared to placebo (exenatide: 662 days [28-735] vs placebo: 669 days [121-721], p=0.9). Only 3 of 22 cats relapsed during the 2-year study — 1 on placebo (day 212) and 2 on exenatide (days 553 and 558).\n\nHowever, exenatide did maintain glycemic control: HbA1c remained stable in the exenatide group (-0.05%) but increased significantly in the placebo group (+2.3%, p=0.03). Both groups lost weight during the study. The low relapse rate overall suggests that active management with low-carbohydrate diets and weight control may itself be important for maintaining remission.","whyItMatters":"Diabetic remission in cats is common but often temporary, and maintaining remission is a major goal in feline diabetes management. While exenatide didn't extend remission duration in this study, its ability to stabilize HbA1c suggests it may help preserve beta cell function. The overall low relapse rate (only 3 of 22 cats) also highlights the importance of dietary management and weight control, which could inform treatment strategies for both veterinary and human diabetes care.","specificNumbers":"","methodology":"This was a placebo-controlled, single-blinded, randomized study of 22 client-owned cats with recent diabetic remission. Cats received either exenatide extended-release (0.13 mg/kg) or saline injections subcutaneously once monthly for up to 2 years. All cats were fed low-carbohydrate diets with supervised weight control. Primary outcomes included remission duration, body weight changes, and HbA1c levels, analyzed with paired t-tests and Mann-Whitney tests.","limitations":"The small sample size (22 cats) limited statistical power, and 9 cats exited prematurely for various reasons, further reducing the analyzable cohort. The study was single-blinded (not double-blinded). The very low relapse rate in both groups suggests that the dietary and weight management protocol may have been the dominant factor, making it difficult to detect an additional drug effect. Results may not generalize to all diabetic cats."},{"rthcId":"RPEP-11106","title":"Recent advances in incretin-based therapy for the treatment of cognitive impairment associated to the type 2 diabetes mellitus: preclinical and clinical studies - a narrative review.","authors":"Giofrè, Federica; Zaffina, Isabella; Pelle, Maria Chiara; Arturi, Franco","year":2025,"journal":"Frontiers in endocrinology, 16, 1696419","doi":"10.3389/fendo.2025.1696419","pmid":"41480353","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11107","title":"An analysis of national news coverage of semaglutide for weight loss.","authors":"Gionfriddo, Michael R; Owens, Katelyn M; Banks, Hannah; Sherigar, Anwitha; Covvey, Jordan R","year":2025,"journal":"Journal of the American Pharmacists Association : JAPhA, 65(1), 102297","doi":"10.1016/j.japh.2024.102297","pmid":"39580054","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11108","title":"Early Fasting Serum Glucose or Weight Reduction With Tirzepatide and Metabolic Outcomes in People With Type 2 Diabetes: A Post Hoc Analysis of the SURPASS Trials.","authors":"Giorgino, Francesco; Lingvay, Ildiko; Van Gaal, Luc F; Sharma, Palash; Rodríguez, Ángel; Kiljański, Jacek; Torcello-Gómez, Amelia; Levine, Joshua A","year":2025,"journal":"Diabetes care, 48(5), 790-798","doi":"10.2337/dc24-2790","pmid":"40100982","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11109","title":"Radiolabeled LHRH and FSH Analogues as Cancer Theranostic Agents: A Systematic Review.","authors":"Giorgio, Anna; Varani, Michela; Lauri, Chiara; Bentivoglio, Valeria; Nayak, Pallavi","year":2025,"journal":"Journal of clinical medicine, 14(21)","doi":"10.3390/jcm14217811","pmid":"41227206","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11110","title":"Modulation of neuropathological pathways by bioactive peptides and proteins/polypeptides: Targeting oxidative stress in neurodegenerative diseases.","authors":"Giri, Sushil; Chandra, Phool","year":2025,"journal":"Neuropeptides, 114, 102563","doi":"10.1016/j.npep.2025.102563","pmid":"41004910","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11111","title":"Application of Lipophilic Prodrug Charge Masking Strategy to Obtain Novel, Potential Oxytocin Prodrugs.","authors":"Gitlin-Domagalska, Agata; Olejnik, Anna; Ruczyński, Jarosław; Starego, Dominika; Ptaszyńska, Natalia; Łęgowska, Anna; Dębowski, Dawid; Gilon, Chaim; Rolka, Krzysztof","year":2025,"journal":"International journal of molecular sciences, 26(10)","doi":"10.3390/ijms26104772","pmid":"40429913","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11112","title":"Expanding the Antiviral Spectrum of Scorpion-Derived Peptides Against Toscana Virus and Schmallenberg Virus.","authors":"Giugliano, Rosa; Zannella, Carla; Della Marca, Roberta; Chianese, Annalisa; Di Clemente, Laura; Monti, Alessandra; Doti, Nunzianna; Cacioppo, Federica; Iovane, Valentina; Montagnaro, Serena; De Grazia, Simona; Galdiero, Massimiliano; De Filippis, Anna","year":2025,"journal":"Pathogens (Basel, Switzerland), 14(7)","doi":"10.3390/pathogens14070713","pmid":"40732759","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11113","title":"Pantinin-Derived Peptides against Veterinary Herpesviruses: Activity and Structural Characterization.","authors":"Giugliano, Rosa; Zannella, Carla; Chianese, Annalisa; Acconcia, Clementina; Monti, Alessandra; Della Marca, Roberta; Pagnini, Ugo; Montagnaro, Serena; Doti, Nunzianna; Isernia, Carla; Galdiero, Massimiliano; Fiorito, Filomena; Russo, Luigi; Iovane, Valentina; De Filippis, Anna","year":2025,"journal":"ChemMedChem, 20(19), e202500333","doi":"10.1002/cmdc.202500333","pmid":"40946226","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11114","title":"The inhibitory potential of three scorpion venom peptides against multidrug-resistant Klebsiella pnemoniae.","authors":"Giugliano, Rosa; Della Marca, Roberta; Chianese, Annalisa; Monti, Alessandra; Donadio, Federica; Esposito, Emanuela; Doti, Nunzianna; Zannella, Carla; Galdiero, Massimiliano; De Filippis, Anna","year":2025,"journal":"Frontiers in microbiology, 16, 1569719","doi":"10.3389/fmicb.2025.1569719","pmid":"40520369","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11115","title":"Development of RALA-Based Mannosylated Nanocarriers for Targeted Delivery of Minicircle DNA Vaccines Encoding HPV-16 Oncogenes.","authors":"Giusti, Andressa; Eusébio, Dalinda; Costa, Matilde; Silveira, Inês; Biswas, Swati; Costa, Diana; Sousa, Ângela","year":2025,"journal":"Vaccines, 14(1)","doi":"10.3390/vaccines14010018","pmid":"41600933","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11116","title":"Bioactive compounds in milk/dairy foods and their value to health at key life stages: Functionality beyond nutrient supply.","authors":"Givens, D Ian","year":2025,"journal":"The Proceedings of the Nutrition Society, 1-11","doi":"10.1017/S0029665125102024","pmid":"41277238","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11117","title":"Semaglutide treatment in hypothalamic obesity: Two-Year outcomes on body composition, appetite, and quality of life.","authors":"Gjersdal, Erlend; Klit, Frederik Østergaard; Schmidt Ettrup, Kåre; Vestergaard, Peter; Nielsen, Eigil Husted; Vistisen, Kristian Nilsson; Müller, Hermann L; Melgaard, Dorte; Dal, Jakob","year":2025,"journal":"Pituitary, 28(5), 93","doi":"10.1007/s11102-025-01564-7","pmid":"40830718","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11118","title":"Left ventricular end-diastolic pressure response to spinal anaesthesia in euvolaemic vascular surgery patients.","authors":"Gkounti, Georgia; Loutradis, Charalampos; Katsioulis, Christos; Nevras, Vasileios; Tzimou, Myrto; Pitoulias, Apostolos G; Argiriadou, Helena; Efthimiadis, Georgios; Pitoulias, Georgios A","year":2025,"journal":"Journal of clinical monitoring and computing, 39(1), 85-93","doi":"10.1007/s10877-024-01220-8","pmid":"39305452","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11119","title":"Indirect crosstalk between signalling pathways activated by CGRP and Piezo1 in human iPSC-derived endothelial cells relevant to migraine.","authors":"Gkouzioti, Vasiliki; Abdollahzadeh, Ali; van den Hil, Francijna; Orlova, Valeria; Giniatullin, Rashid; van den Maagdenberg, Arn M J M; Frimat, Jean-Philippe","year":2025,"journal":"Cephalalgia : an international journal of headache, 45(12), 3331024251404478","doi":"10.1177/03331024251404478","pmid":"41410740","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11120","title":"Systemic and gut microbiome changes with metformin and liraglutide in youth-onset type 2 diabetes: the MIGHTY study.","authors":"Glaros, Sophia B; Mishra, Sidharth P; Jain, Shalini; Davis, Faith S; Gabel, Scott A; Mueller, Geoffrey A; Jarmusch, Alan K; Mabundo, Lilian; Courville, Amber B; Walter, Mary F; Walter, Peter J; Overdahl, Kirsten E; Yadav, Hariom; Chung, Stephanie T","year":2025,"journal":"Gut microbes, 17(1), 2558071","doi":"10.1080/19490976.2025.2558071","pmid":"41020378","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11121","title":"Impact of glucagon-like peptide-1 receptor agonists on the incidence of atrial fibrillation.","authors":"Glaser, Krzysztof; Glaser, Wojciech; Marino, Luca; Ruchala, Marek; Bilotta, Federico","year":2025,"journal":"World journal of cardiology, 17(7), 107510","doi":"10.4330/wjc.v17.i7.107510","pmid":"40741027","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11122","title":"Prospective Evaluation of the Cardiovascular Effects of BRAF and MEK Inhibitors in Patients With Melanoma.","authors":"Glen, Claire; Dobbin, Stephen J H; Mangion, Kenneth; Henderson, Alasdair; Brooksbank, Katriona; Coats, Caroline J; Epstein, Frederick H; Kellman, Peter; Butler, Elaine; Evans, Thomas R Jeffry; Jones, Rob; McClure, John; Roditi, Giles; Tan, Yun Yi; Waterston, Ashita; Welsh, Paul; Petrie, Mark C; Lang, Ninian N","year":2025,"journal":"JACC. CardioOncology, 7(7), 852-866","doi":"10.1016/j.jaccao.2025.08.006","pmid":"41065626","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11123","title":"Mapping of quorum sensing interaction network of commensal and pathogenic staphylococci.","authors":"Gless, Bengt H; Sereika-Bejder, Benjamin S; Jensen, Iben; Bojer, Martin S; Tsiko, Katerina; Schmied, Sabrina H; Vitolo, Ludovica; Toledo-Silva, Bruno; De Vliegher, Sarne; Ingmer, Hanne; Olsen, Christian A","year":2025,"journal":"mBio, 16(8), e0096725","doi":"10.1128/mbio.00967-25","pmid":"40667988","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Systematic mapping of 280 quorum sensing interactions across 21 staphylococcal species revealed substantial differences in inhibitory potencies between human- and animal-associated species. Six new autoinducing peptides (RiPPs) were identified.\n\nS. simulans AIPs showed strong potential as QS inhibitors and were used as a starting point for structure-activity relationship optimization, yielding the most potent inhibitors reported to date for S. epidermidis and S. lugdunensis. An S. simulans AIP showed no evidence of acquired suppression of its inhibitory effect in resistance testing. A peptide inhibitor successfully attenuated MRSA skin infection in a mouse model, demonstrating in vivo anti-virulence activity.","whyItMatters":"MRSA kills tens of thousands of people annually, and antibiotic resistance continues to grow. Quorum sensing inhibition is a fundamentally different approach — instead of trying to kill bacteria (which drives resistance), it disarms them by blocking their communication peptides. This study provides the most comprehensive map of staphylococcal peptide interactions and delivers potent inhibitors with demonstrated in vivo activity.","specificNumbers":"","methodology":"The researchers identified six new AIPs and synthesized all known staphylococcal AIPs covering 21 species. They tested all 280 QS interactions using reporter assays divided by human and animal host association. S. simulans AIPs were selected for structure-activity optimization. Resistance development was assessed using serial passage assays. In vivo efficacy was tested in a mouse MRSA skin infection model.","limitations":"The in vivo demonstration was limited to a skin infection model; systemic MRSA infections were not tested. The peptide inhibitors are macrocyclic structures that may face pharmacokinetic challenges for systemic delivery. While no resistance was detected in initial testing, longer-term resistance evolution studies would be needed. The clinical path from quorum sensing inhibitor to approved anti-MRSA therapy remains long."},{"rthcId":"RPEP-11124","title":"Modulation of GLP-1 signalling as an innovative strategy counteracting the onset of heart failure: Potential for natural compound supplementation.","authors":"Gliozzi, Micaela; Coppoletta, Anna Rita; Cardamone, Antonio; Carresi, Cristina; Mollace, Rocco; Musolino, Vincenzo; Mollace, Vincenzo","year":2025,"journal":"Pharmacological research, 216, 107744","doi":"10.1016/j.phrs.2025.107744","pmid":"40268125","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11125","title":"Retro-inversion imparts antimycobacterial specificity to host defense peptides.","authors":"Glossop, Hugh D; Gebretsadik, Gebremichal; Sultana, Sabiha; Biswas, Diptomit; Schacht, Nathan A; Yennawar, Neela H; Rather, Muzafar Ahmad; Baughn, Anthony D; Medina, Scott H","year":2025,"journal":"Nature communications, 17(1), 469","doi":"10.1038/s41467-025-67162-0","pmid":"41354737","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11126","title":"Glucagon-like peptide-1 receptor agonists are associated with fewer major adverse cardiovascular and limb events in patients with moderate peripheral arterial disease.","authors":"Go, Catherine C; Annie, Frank; Drabish, Kerry; Eslami, Mohammad H","year":2025,"journal":"Journal of vascular surgery, 82(3), 1024-1032.e2","doi":"10.1016/j.jvs.2025.05.037","pmid":"40484062","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11127","title":"Characterisation of neurogenic lipolytic responses in white adipose tissue ex vivo.","authors":"Goddard, Kayleigh E; Fountain, Samuel J","year":2025,"journal":"British journal of pharmacology, 182(9), 1975-1988","doi":"10.1111/bph.17445","pmid":"39894466","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11128","title":"Evaluation of the effects of metformin on gut functions and microbiota and their contribution to improving glucose tolerance in diabetic mice.","authors":"Godet, Murielle; Meugnier, Emmanuelle; Vitalis, Oriane; Bendridi, Nadia; Vieille-Marchiset, Aurélie; Vega, Nathalie; Benoit, Bérengère; Pinteur, Claudie; Rainteau, Dominique; Cheillan, David; Michalski, Marie-Caroline; Chikh, Karim; Vidal, Hubert","year":2025,"journal":"Molecular metabolism, 102, 102263","doi":"10.1016/j.molmet.2025.102263","pmid":"41033655","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11129","title":"Impact of Natriuretic Peptide and Prior Hospitalization in Patients With Severe Mitral Regurgitation: COAPT Trial.","authors":"Goel, Sachin S; Guha, Ashrith; Lindenfeld, JoAnn; Abraham, William T; Kar, Saibal; Kapadia, Samir R; Little, Stephen H; Lim, D Scott; Reardon, Michael J; Kleiman, Neal S; Aiyer, Janani; Kotinkaduwa, Lak N; Mack, Michael J; Stone, Gregg W","year":2025,"journal":"Circulation. Cardiovascular interventions, 18(7), e015192","doi":"10.1161/CIRCINTERVENTIONS.125.015192","pmid":"40357542","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11130","title":"Perspectives on C-Type Natriuretic Peptide in Cardiometabolic Disease.","authors":"Goetze, Jens P; Yanagisawa, Hiromu; Kinoshita, Hideyuki; Burnett, John; Nyberg, Michael; Nishikimi, Toshio","year":2025,"journal":"Journal of the American Heart Association, 14(24), e046011","doi":"10.1161/JAHA.125.046011","pmid":"41378499","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11131","title":"Effects of GLP-1 Analogues and Agonists on the Gut Microbiota: A Systematic Review.","authors":"Gofron, Krzysztof Ksawery; Wasilewski, Andrzej; Małgorzewicz, Sylwia","year":2025,"journal":"Nutrients, 17(8)","doi":"10.3390/nu17081303","pmid":"40284168","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 38 included studies, GLP-1 receptor agonists demonstrated notable impacts on gut microbiota composition, richness, and diversity:\n\n- **Liraglutide**: Promoted growth of beneficial genera with metabolic functions\n- **Exenatide/Exendin-4**: Increased metabolism-associated genera in animals, but mixed results in humans with some pro-inflammatory genera also increasing\n- **Dulaglutide**: Significantly increased Bacteroides, Akkermansia, and Ruminococcus — genera associated with improved metabolic profiles\n- **Semaglutide**: Increased Akkermansia muciniphila (positive metabolic functions) but decreased overall microbial diversity; results varied considerably across studies due to population differences and study duration","whyItMatters":"The gut microbiome influences metabolism, inflammation, appetite, and even brain function. Understanding how GLP-1 drugs alter gut bacteria could reveal new mechanisms explaining their broad health benefits — from weight loss to cardiovascular protection. It could also help predict which patients will respond best and guide microbiome-targeted combination therapies.","specificNumbers":"","methodology":"PRISMA-guided systematic review searching for studies on the effects of GLP-1 analogues on gut microbiota composition, richness, and abundance. Both animal and human studies were included. Thirty-eight studies met inclusion criteria. Results were synthesized narratively by drug type.","limitations":"Results varied considerably between studies due to differences in study populations, drug doses, treatment durations, and microbiome analysis methods. Most human studies were small. The systematic review synthesized results narratively rather than through meta-analysis, limiting quantitative conclusions. It remains unclear whether microbiome changes are a cause or consequence of the metabolic improvements from GLP-1 drugs. Animal model findings may not directly translate to human microbiome responses."},{"rthcId":"RPEP-11132","title":"Single and Combined Impact of Semaglutide, Tirzepatide, and Metformin on β-Cell Maintenance and Function Under High-Glucose-High-Lipid Conditions: A Comparative Study.","authors":"Gojani, Esmaeel Ghasemi; Wang, Bo; Li, Dongping; Kovalchuk, Olga; Kovalchuk, Igor","year":2025,"journal":"International journal of molecular sciences, 26(1)","doi":"10.3390/ijms26010421","pmid":"39796271","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11133","title":"The Impact of Liraglutide, a GLP-1 Receptor Agonist, on High Glucose-Induced Inflammation, Apoptosis, Oxidative Stress, and NLRP3 Signaling.","authors":"Gokce, Mustafa; Ozturk Civelek, Dilek; Vidin Sen, Aylin; Guler, Eray Metin; Civelek, Erkan; Uydes Dogan, Birsel Sonmez; Alp Yildirim, F Ilkay","year":2025,"journal":"Cell biochemistry and biophysics, 83(3), 3619-3632","doi":"10.1007/s12013-025-01742-1","pmid":"40216698","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11134","title":"Cost-effectiveness analysis of ubrogepant, rimegepant, and zavegepant for acute migraine treatment vs usual care.","authors":"Gokhale, Pooja; Villa Zapata, Lorenzo","year":2025,"journal":"The American journal of managed care, 31(11), e322-e328","doi":"10.37765/ajmc.2025.89822","pmid":"41289290","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11135","title":"Evaluation of the efficacy of a biomimetic peptide solution for rejuvenation of donor scalp and as storage media for hair follicle grafts during FUE hair transplantation.","authors":"Gold, Michael; Zaman, Ungku Mohd Shahrin Mohd; Chouksey, Vinay; Gosavi, Mahesh","year":2025,"journal":"Journal of cosmetic and laser therapy : official publication of the European Society for Laser Dermatology, 27(3), 64-70","doi":"10.1080/14764172.2025.2468499","pmid":"40228316","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11136","title":"Glucagon-like peptide-1 receptor agonist use prior to spinal surgery results in reduced postoperative length of stay: A propensity-score matched analysis.","authors":"Goldman, Samuel N; Mani, Kyle; Scharfenberger, Thomas; Kleinbart, Emily; Hui, Aaron T; De la Garza Ramos, Rafael; Fourman, Mitchell S; Eleswarapu, Ananth S","year":2025,"journal":"North American Spine Society journal, 22, 100612","doi":"10.1016/j.xnsj.2025.100612","pmid":"40470002","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Preoperative GLP-1 receptor agonist use was associated with a significant reduction in median postoperative length of stay: 3 days vs 4 days (p=0.036). This effect was particularly pronounced among patients undergoing lumbar fusion.\n\nNo significant differences were observed between GLP-1RA users and controls in operating room time, 90-day reoperation rates, 90-day readmission rates, or nonroutine discharge rates, suggesting that GLP-1RA use did not negatively impact other surgical outcomes.","whyItMatters":"Hospital length of stay after spinal surgery is a major driver of healthcare costs and patient recovery. If GLP-1 receptor agonists — already taken by millions for diabetes and weight loss — also help patients recover faster from surgery, it could have significant implications for surgical planning and preoperative optimization, especially for the large population of overweight and diabetic patients who commonly need spinal procedures.","specificNumbers":"","methodology":"This was a retrospective, propensity score-matched analysis of adult patients undergoing spinal decompression and/or fusion at an urban academic spine center over 5 years. A 1:4 nearest-neighbor matching algorithm paired 277 GLP-1RA users with 1,108 controls, matching on age, sex, BMI, procedure type, comorbidities, and use of other diabetes medications. Outcomes were assessed using multivariate logistic regression for binary outcomes and the Mann-Whitney U test for continuous variables.","limitations":"This is a retrospective single-center study, which limits generalizability and cannot prove causation. The study could not determine whether the shorter hospital stays were specifically due to GLP-1RA pharmacological effects or related lifestyle factors. The duration and dosing of GLP-1RA use before surgery were not analyzed. Additionally, the study could not differentiate between specific GLP-1RA drugs, and the predominantly female cohort (62%) may not represent all spinal surgery patients."},{"rthcId":"RPEP-11137","title":"Obesity Management in Youth with Duchenne Muscular Dystrophy: A Review of Metformin and Alternative Pharmacotherapies.","authors":"Goldman, Victoria; Ryabets-Lienhard, Anna; Howard, Lauren; Kohli, Roshni; Sousa, Emily; Patel, Priya; Marpuri, Ian; Vidmar, Alaina P","year":2025,"journal":"Childhood obesity (Print), 21(2), 103-112","doi":"10.1089/chi.2024.0297","pmid":"39392010","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11138","title":"Triple Agonism Based Therapies for Obesity.","authors":"Goldney, Jonathan; Hamza, Malak; Surti, Farhaana; Davies, Melanie J; Papamargaritis, Dimitris","year":2025,"journal":"Current cardiovascular risk reports, 19(1), 18","doi":"10.1007/s12170-025-00770-z","pmid":"40741227","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11139","title":"Slimming the risks: GLP-1 receptor agonist therapy may reduce in-hospital complications and hospital readmissions rates for hip fractures compared to obese patients not on these medications.","authors":"Goldstein, Amelia R; Olson, Danielle; Leucht, Phillip; Tejwani, Nirmal; Ganta, Abhishek; Konda, Sanjit; Egol, Kenneth A","year":2025,"journal":"European journal of orthopaedic surgery & traumatology : orthopedie traumatologie, 35(1), 377","doi":"10.1007/s00590-025-04477-0","pmid":"40892123","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11140","title":"The impact of semaglutide on liver fat assessed by serial cardiac CT scans in patients with type 2 diabetes: Results from STOP trial.","authors":"Golub, Ilana S; Manubolu, Venkat S; Aldana-Bitar, Jairo; Dahal, Suraj; Verghese, Dhiran; Alalawi, Luay; Krishnan, Srikanth; Kianoush, Sina; Benzing, Travis; Ichikawa, Keishi; Kinninger, April; Fazlalizadeh, Hooman; Pourafkari, Leili; Ahmad, Khadije; Susarla, Shriraj; Mangaoang, Czarina; Ghanem, Ahmed K; Javier, Denise Alison; Hamal, Sajad; Roy, Sion K; Budoff, Matthew J","year":2025,"journal":"Nutrition, metabolism, and cardiovascular diseases : NMCD, 35(9), 104036","doi":"10.1016/j.numecd.2025.104036","pmid":"40287313","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11141","title":"Obesity medications in patients with recurrent weight gain or suboptimal clinical response following bariatric surgery: a meta-analysis.","authors":"Golzarand, Mahdieh; Toolabi, Karamollah; Mirmiran, Parvin","year":2025,"journal":"International journal of obesity (2005), 49(9), 1676-1687","doi":"10.1038/s41366-025-01807-4","pmid":"40382437","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11142","title":"Association Between the Magnitude of Glycemic Control and Body Weight Loss With GLP-1 Receptor Agonists and Risk of Atherosclerotic Cardiovascular Disease: A Systematic Review and Meta-analyses of Randomized Diabetes Cardiovascular Outcomes Trials.","authors":"Gomes, Daniel A; Presume, João; de Araújo Gonçalves, Pedro; Almeida, Manuel Sousa; Mendes, Miguel; Ferreira, Jorge","year":2025,"journal":"Cardiovascular drugs and therapy, 39(2), 337-345","doi":"10.1007/s10557-024-07547-3","pmid":"38214869","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11143","title":"State of the Art Review: Glucagon-Like Peptide-1 in Obesity-Related Asthma.","authors":"Gomez, Destiny R; Swartzman, Isaac; Linderholm, Angela; Cummings, Bethany P; Zeki, Amir A; Sundar, Krishna M; Kenyon, Nicholas J","year":2025,"journal":"Lung, 203(1), 108","doi":"10.1007/s00408-025-00861-z","pmid":"41359186","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11144","title":"Structure-Guided Design of Peptide Inhibitors Targeting Class I Viral Fusion Proteins.","authors":"Gonepudi, Narendra Kumar; Baffour Awuah, Harry; Xu, Wang; Katte, Revansiddha H; Lu, Maolin","year":2025,"journal":"Pathogens (Basel, Switzerland), 15(1)","doi":"10.3390/pathogens15010032","pmid":"41599016","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11145","title":"Xenin-Derived Peptides: Multifaceted Regulators and Therapeutic Innovations in Metabolic Diseases.","authors":"Gong, Binbin; Liu, Xiyu; Hu, Guoqiang; Li, Tongtong; Chen, Fei; Sun, Xueqing; Sun, Lidan; Xu, Yinghe","year":2025,"journal":"Drug design, development and therapy, 19, 11799-11815","doi":"10.2147/DDDT.S565077","pmid":"41479596","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11146","title":"GLP-1 receptor agonists: exploration of transformation from metabolic regulation to multi-organ therapy.","authors":"Gong, Bing; Li, Couwen; Shi, Zhuang'e; Wang, FuPing; Dai, Ruanxian; Chen, Guobing; Su, Heng","year":2025,"journal":"Frontiers in pharmacology, 16, 1675552","doi":"10.3389/fphar.2025.1675552","pmid":"41019986","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 receptor agonists have expanded far beyond their original diabetes/obesity indications. The review identifies four key molecular mechanisms underlying their multi-organ effects: immune/inflammatory pathway modulation, autophagy and pyroptosis regulation, endoplasmic reticulum stress alleviation, and gut microbiome interaction.\n\nClinical evidence now supports cardiovascular and renal protection (with regulatory approvals). Emerging data suggests potential benefits in liver disease, obstructive sleep apnea, chronic respiratory disorders, neurodegenerative diseases, psychiatric conditions, reproductive dysfunction, obesity-associated cancers, and sepsis — though these applications remain investigational.","whyItMatters":"GLP-1 receptor agonists are arguably the most important peptide drug class of this era, and their therapeutic reach keeps expanding. This review maps the transformation from a diabetes medication to a potential treatment for conditions across virtually every organ system. Understanding the four underlying molecular mechanisms explains why a single peptide can have such wide-ranging effects and guides which new indications are most promising for clinical development.","specificNumbers":"4 key mechanisms identified · Cardiovascular + renal protection approved · 8+ emerging indications · Multiple organ systems affected · Immune, autophagy, ER stress, microbiome pathways","methodology":"Comprehensive narrative review synthesizing evidence from preclinical mechanistic studies and clinical trials on GLP-1RA effects across multiple organ systems. The review integrates molecular mechanism data with clinical outcome evidence to build a framework for understanding GLP-1RA multi-organ potential.","limitations":"This is a narrative review, not a systematic review or meta-analysis. Most of the expanded indications beyond cardiovascular and renal protection are based on early or preclinical data. The review does not critically evaluate the strength of evidence for each new indication. Publication bias may favor positive findings. The question of whether GLP-1RA benefits in non-metabolic diseases are direct drug effects or secondary to weight loss and metabolic improvement is not always clearly addressed."},{"rthcId":"RPEP-11147","title":"Multiple analysis based on dual-mode anion-exchange chromatography strategy reveals significant impact of charge heterogeneity on structure and function of dulaglutide.","authors":"Gong, Feifei; Shen, Zhenduo; Sun, Baiping; Deng, Lili; Han, Lina; Xu, Hui; Dou, Changlin","year":2025,"journal":"International journal of biological macromolecules, 329(Pt 1), 147808","doi":"10.1016/j.ijbiomac.2025.147808","pmid":"40976302","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11148","title":"Risk of biliary diseases in patients with type 2 diabetes or obesity treated with tirzepatide: A meta-analysis.","authors":"Gong, Jie; Gao, Fengwei; Jiang, Kangyi; Xie, Qingyun; Zhao, Xin; Lei, Zehua","year":2025,"journal":"Journal of diabetes investigation, 16(1), 83-92","doi":"10.1111/jdi.14340","pmid":"39569606","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11149","title":"The impact of probiotic supplementation on gastric motility and nutrient absorption in elderly patients with Gastrointestinal disorders.","authors":"Gong, Pingting; Tang, Xuehong","year":2025,"journal":"BMC gastroenterology, 25(1), 192","doi":"10.1186/s12876-025-03740-2","pmid":"40114066","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11150","title":"Impact of GLP-1 receptor agonists on cardiovascular outcomes in heart failure with preserved ejection fraction (HFpEF): systematic review and meta-analysis.","authors":"Gonzales-Uribe, Antony; Ruiz-Cortez, Renato; Collantes-Silva, Nicole; Olivero, Lorenzo; Agarwal, Raksheeth; Arambulo-Castillo, Sebastian; Garcia-Geng, Alonso; Lyu, Xiajie; Mendoza-Quispe, Daniel; Becerra-Gonzales, Victor; Butrous, Hoda","year":2025,"journal":"Clinical research in cardiology : official journal of the German Cardiac Society","doi":"10.1007/s00392-025-02710-8","pmid":"40637782","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 6 studies (5 RCTs, 1 cohort; n=4,043), GLP-1RAs reduced the composite of all-cause mortality and HF hospitalization by 27% (HR 0.73; 95% CI: 0.60-0.90; I²=0%). HF hospitalizations alone were reduced by 43% (HR 0.57; 95% CI: 0.32-1.00). All-cause mortality alone was not significantly reduced (HR 0.81; 95% CI: 0.58-1.14). Subgroup analysis showed greater benefits in patients with atrial fibrillation. Five studies evaluated semaglutide and one tirzepatide. RCTs showed low risk of bias.","whyItMatters":"HFpEF affects roughly half of all heart failure patients and has been called 'the greatest unmet need in cardiovascular medicine.' Unlike heart failure with reduced ejection fraction, HFpEF has had almost no effective drug treatments — until recently. SGLT2 inhibitors showed the first breakthrough; now GLP-1RAs appear to offer a second therapeutic option. For the millions of HFpEF patients worldwide, this represents a significant expansion of treatment options.","specificNumbers":"","methodology":"Systematic review and meta-analysis of PubMed, Scopus, Embase, and Web of Science through December 2024. Six studies (5 RCTs, 1 cohort) comparing GLP-1RAs to placebo or other hypoglycemic agents in HFpEF patients were included. GRADE and Risk of Bias assessments evaluated evidence quality. Random-effects meta-analysis pooled hazard ratios with subgroup analyses by patient characteristics.","limitations":"Only 6 studies with 4,043 patients — modest for a meta-analysis. Five of six studies used semaglutide, so this may represent a drug-specific rather than class effect. The mortality reduction (HR 0.81) did not reach significance, likely due to limited statistical power. The single cohort study introduces observational bias. The HF hospitalization confidence interval barely reached significance (upper bound 1.00). Follow-up durations varied across studies."},{"rthcId":"RPEP-11151","title":"Defensin-Rich Platelets Drive Pro-Tumorigenic Programs in Pancreatic Adenocarcinoma.","authors":"Gonzalez-Ruiz, Jonathan; Sarmiento-Casas, Miryam; Bahena-Ocampo, Ivan; Espinosa, Magali; Ceballos-Cancino, Gisela; Vazquez-Santillan, Karla; Maldonado, Vilma; Melendez-Zajgla, Jorge","year":2025,"journal":"International journal of molecular sciences, 26(22)","doi":"10.3390/ijms262210898","pmid":"41303383","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11152","title":"Rapamycin reveals neuropeptide Y as a regulator of senescence and inflammatory pathways in arthritis.","authors":"González-Chávez, Susana Aideé; Chaparro-Barrera, Eduardo; Loya-Rivera, Mario; Rodríguez-Castillo, Alejandra Jazmín; Prieto-Carrasco, Rodrigo; Aguilera, Renato J; Betancourt, Ana P; Mohl, Jonathon E; Ruizesparza-Hinojos, Daniel Alberto; Ramírez-Pérez, Sergio de Jesús; Bermúdez, Mercedes; Pacheco-Tena, César","year":2025,"journal":"Neuropeptides, 112, 102533","doi":"10.1016/j.npep.2025.102533","pmid":"40554049","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Transcriptomic analysis of rapamycin-treated arthritic mice identified neuropeptide Y (NPY) as a differentially expressed gene connecting senescence and inflammation pathways. Rapamycin reduced NPY protein levels along with TNF and the senescence marker β-galactosidase, and also modulated NPY receptor expression (NPY1R, NPY2R) and autophagy genes (Sirt1, Sirt6, Lc3b).\n\nIn vitro validation showed that silencing NPY in fibroblast-like synoviocytes (the cells lining arthritic joints) significantly reduced expression of three major inflammatory cytokines — TNF-α, IL-1β, and IL-6 — which are the hallmarks of the senescence-associated secretory phenotype (SASP). NPY silencing also downregulated its own receptors and increased Sirt1 expression, a longevity-associated gene.","whyItMatters":"Rheumatoid arthritis affects about 1% of the global population, and current treatments focus on broadly suppressing the immune system. Identifying NPY as a molecular connector between cellular aging and joint inflammation opens a more targeted therapeutic avenue. If NPY or its receptors can be selectively modulated, it could address both the inflammatory and degenerative aspects of arthritis simultaneously — something current treatments don't achieve.","specificNumbers":"","methodology":"Collagen-induced arthritis was established in DBA/1 mice, followed by 40 days of rapamycin treatment. RNA sequencing and bioinformatic analyses identified differentially expressed genes and altered pathways. Results were validated by RT-qPCR and immunohistochemistry. Functional assays using NPY gene silencing in fibroblast-like synoviocytes (FLS) confirmed the peptide's role in regulating inflammatory and senescence pathways.","limitations":"This is a preclinical study using a collagen-induced arthritis mouse model, which doesn't fully replicate human RA. The in vitro NPY silencing experiments were performed in isolated synoviocytes, which may behave differently in the complex joint environment. The study did not test whether directly targeting NPY in vivo (rather than using rapamycin) would reduce arthritis severity. Rapamycin has broad effects, so the specific contribution of NPY modulation to the overall therapeutic effect is unclear."},{"rthcId":"RPEP-11153","title":"His-tagged pro-apoptotic peptides: enhancing cell internalization and anticancer effect in vitro.","authors":"González-Cruz, Aldo O; Pérez-Trujillo, José Juan; Balderas-Rentería, Isaías; Villa-Cedillo, Sheila Adela; De-León-Covarrubias, Ulises Edgardo; Arredondo-Espinoza, Eder","year":2025,"journal":"Apoptosis : an international journal on programmed cell death, 30(11-12), 3105-3114","doi":"10.1007/s10495-025-02180-3","pmid":"40963080","tags":[],"studyType":"in-vitro","evidenceStrength":"low","keyFinding":"Adding a histidine tag (His-tag) to pro-apoptotic peptides improved their ability to enter cancer cells in laboratory tests. The KLAK-H peptide showed the strongest anticancer effect against A-549 lung cancer cells, with an IC50 of 33.3 µM, while the EGFR-targeted version NRPD-KLAK-H had an IC50 of 40.9 µM.\n\nBoth KLAK-H and NRPD-KLAK-H successfully entered cancer cells (confirmed by immunofluorescence) and induced apoptosis (confirmed by TUNEL assays). However, the CTMP4-based peptides showed poor cellular uptake regardless of targeting modifications.\n\nInterestingly, the EGFR-targeting component (NRPD) did not enhance the anticancer effect as expected — the simpler His-tagged KLAK peptide actually performed slightly better than the targeted version. This suggests that short poly-histidine sequences alone can meaningfully improve cellular uptake of pro-apoptotic peptides.","whyItMatters":"Getting cancer-killing peptides inside tumor cells is one of the biggest challenges in peptide drug development. This study shows that a simple chemical modification — adding a histidine tag — can improve cellular uptake of pro-apoptotic peptides without complex targeting systems. While the EGFR-targeting strategy didn't work as hoped, the His-tag finding offers a practical approach to enhancing peptide delivery for cancer therapy.","specificNumbers":"KLAK-H IC50: 33.3 µM · NRPD-KLAK-H IC50: 40.9 µM · Tested on A-549 lung cancer cells · His-tag improved internalization · CTMP4 variants: poor uptake","methodology":"Researchers designed pro-apoptotic peptides with His-tag modifications and EGFR-targeting sequences, then tested them against A-549 non-small cell lung cancer cells. Cell viability was measured using MTT assays, apoptosis was confirmed with TUNEL assays, and cellular uptake was visualized with immunofluorescence microscopy.","limitations":"This is an in vitro study using a single cancer cell line (A-549). The IC50 values (33–41 µM) are relatively high for drug candidates, which may limit clinical applicability. No animal testing was performed. The EGFR-targeting strategy did not improve efficacy over the non-targeted version, raising questions about the design approach. Selectivity for cancer cells over normal cells was not thoroughly assessed."},{"rthcId":"RPEP-11154","title":"The influence of pharmacodynamics and pharmacokinetics on the antimigraine efficacy and safety of novel anti-CGRPergic pharmacotherapies: a narrative review.","authors":"González-Hernández, Abimael; Villalón, Carlos M","year":2025,"journal":"Expert opinion on drug metabolism & toxicology, 21(1), 41-52","doi":"10.1080/17425255.2024.2409253","pmid":"39319681","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11155","title":"Glucagon-like peptide-1 receptor agonists and muscle health: potential role in sarcopenia prevention and treatment.","authors":"González-Luis, Ainhoa; Llinares-Arvelo, Vicente; Martínez-Alberto, Carlos E; Hernández-Carballo, Carolina; Mora-Fernández, Carmen; Navarro-González, Juan F; Donate-Correa, Javier","year":2025,"journal":"European journal of endocrinology, 193(5), R31-R44","doi":"10.1093/ejendo/lvaf223","pmid":"41166543","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11156","title":"Exenatide and glucagon co-infusion increases myocardial glucose uptake and improves markers of diastolic dysfunction in adults with type 2 diabetes.","authors":"Goodman, James; Schain, Martin; Di Stefano, Giovanni; Lupson, Victoria; Horn, Tracy; Hill, Marion; Manavaki, Roie; Fryer, Timothy D; Bumanlag-Amis, Elaine; Jalaludeen, Navazh; Jermutus, Lutz; Johansson, Edvin; Heurling, Kerstin; Haraldsson, Henrik; Evans, Mark; Cheriyan, Joseph; Johansson, Lars; Ambery, Philip; Wilkinson, Ian B","year":2025,"journal":"Scientific reports, 15(1), 21404","doi":"10.1038/s41598-025-04559-3","pmid":"40593987","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11157","title":"Adipocentric Strategy for the Treatment of Type 2 Diabetes Mellitus.","authors":"Gorgojo-Martínez, Juan J","year":2025,"journal":"Journal of clinical medicine, 14(3)","doi":"10.3390/jcm14030678","pmid":"39941348","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11158","title":"Engineering unnatural amino acids in peptide linkers enables cathepsin-selective antibody-drug conjugates for HER2-positive breast cancer.","authors":"Gorzeń, Oliwia; Łęcka, Maria; Ćwilichowska-Puślecka, Natalia; Majchrzak, Martyna; Horbach, Natalia; Wiśniewski, Jerzy; Jakimowicz, Piotr; Szpot, Paweł; Zawadzki, Marcin; Dołęga-Kozierowski, Bartosz; Kasprzak, Piotr; Turk, Boris; Drąg, Marcin; Groborz, Katarzyna M; Matkowski, Rafał; Poręba, Marcin","year":2025,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 387, 114269","doi":"10.1016/j.jconrel.2025.114269","pmid":"41015259","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11159","title":"Metabolic Dysfunction-Associated Steatotic Liver Disease Complicated by Diabetes: Pathophysiology and Emerging Therapies.","authors":"Goto, Hisanori; Takamura, Toshinari","year":2025,"journal":"Journal of obesity & metabolic syndrome, 34(3), 224-238","doi":"10.7570/jomes25017","pmid":"40537153","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11160","title":"Genome of venomous caterpillar Doratifera vulnerans reveals recruitment of immune peptides and their adaptation as pain-inducing toxins.","authors":"Goudarzi, Mohaddeseh H; Robinson, Samuel D; Cardoso, Fernanda C; Suryamohan, Kushal; Lawrence, Nicole; Eagles, David A; Hoang, Huy N; Vetter, Irina; Fairlie, David P; Seshagiri, Somasekar; King, Glenn F; Walker, Andrew A","year":2025,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 122(49), e2513640122","doi":"10.1073/pnas.2513640122","pmid":"41325521","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The near-chromosomal genome assembly of D. vulnerans identified 115 gene loci encoding polypeptide venom toxins, including multigene families and single-copy genes. A gene cluster on chromosome 7 encodes both pain-causing venom peptides and cecropin family antimicrobial peptides.\n\nKey peptide characterization:\n- Dv13 (trace component, cecropin-like): potently inhibited Gram-negative bacteria and fungi but only weakly permeabilized mammalian neuronal membranes (EC50 >100 µM)\n- Dv11 and Dv12 (abundant in venom, sequence-divergent): potently disrupted mammalian neuronal membranes (EC50 as low as 190 nM — over 500-fold more potent than Dv13) but had reduced antimicrobial activity\n\nPositive selection analysis confirmed strong evolutionary pressure driving the functional transition from immune defense to pain induction.","whyItMatters":"This study provides a rare, clear example of how new biological functions evolve from existing ones — immune peptides becoming venom toxins through gene duplication and adaptive mutation. For peptide science, it reveals the structural features that determine whether a peptide kills bacteria or disrupts nerve cells, providing valuable design principles for both antimicrobial drug development (what makes cecropins effective?) and pain research (what makes peptides neurotoxic?). The 500-fold difference in neuronal potency between closely related peptides is a striking structure-activity relationship.","specificNumbers":"","methodology":"Researchers generated a near-chromosomal-level genome assembly for D. vulnerans. Gene loci encoding venom toxins were identified through genomic and transcriptomic analysis. Evolutionary relationships between venom peptides and cecropin immune peptides were established through phylogenetic analysis and positive selection testing. Functional characterization included bacterial and fungal growth inhibition assays (antimicrobial activity), mammalian neuronal membrane permeabilization assays (pain-related activity), and EC50 determination for key peptides.","limitations":"The functional characterization focused on three peptides (Dv11, Dv12, Dv13) from the 115 identified venom gene loci — the vast majority remain uncharacterized. The mammalian neuronal membrane assay measures permeabilization in vitro, which may not fully replicate the pain experience in intact organisms. The evolutionary pathway from immune peptide to toxin is inferred from sequence analysis and selection pressures, not directly observed. The study is in an insect (caterpillar) system, and the relevance of these specific peptides to human therapeutics requires further investigation."},{"rthcId":"RPEP-11161","title":"Early-Onset Obesity and Tirzepatide Treatment: A Post Hoc Analysis of the SURMOUNT Clinical Trials.","authors":"Gourgari, Evgenia; Srivastava, Gitanjali; Kelly, Aaron S; Mojdami, Donna; Cao, Dachuang; Murphy, Madhumita A; Karanikas, Chrisanthi A; Lee, Clare J","year":2025,"journal":"Obesity (Silver Spring, Md.), 33(9), 1668-1679","doi":"10.1002/oby.24348","pmid":"40717199","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across the SURMOUNT-1, SURMOUNT-3, and SURMOUNT-4 trials (N=3,782), participants with early-onset obesity (diagnosed before age 25) had distinct baseline profiles compared to later-onset obesity: higher BMI (40 vs. 37 kg/m²), larger waist circumference (118 vs. 112 cm), longer obesity duration (20 vs. 11 years), but paradoxically lower HbA1c (5.48% vs. 5.60%), triglycerides (120 vs. 130 mg/dL), and systolic blood pressure (121 vs. 125 mmHg).\n\nDespite these baseline differences, tirzepatide treatment produced remarkably similar outcomes in both groups at 72 weeks: body weight reduction (-23% vs. -22%), waist circumference reduction (-22 vs. -19 cm), HbA1c improvement (-0.51% vs. -0.52%), triglyceride reduction (-32% vs. -31%), and systolic blood pressure reduction (-8 vs. -8 mmHg). These consistent results were replicated across all three SURMOUNT trials.","whyItMatters":"Early-onset obesity has been linked to more severe metabolic complications and is sometimes perceived as harder to treat. This analysis provides reassurance that tirzepatide is equally effective for people who have lived with obesity since childhood or young adulthood, even though they tend to start with higher BMI and have had obesity for much longer.","specificNumbers":"","methodology":"This was a post hoc analysis pooling data from three randomized, placebo-controlled SURMOUNT clinical trials. Participants (N=3,782) were divided into early-onset obesity (diagnosed before age 25) and later-onset obesity subgroups. Researchers compared baseline characteristics and changes in body weight and cardiometabolic risk factors at 72 or 88 weeks of tirzepatide versus placebo treatment.","limitations":"This was a post hoc analysis, not a pre-specified comparison, so results should be interpreted with caution. Age of obesity onset was self-reported and may be inaccurate. The trials may not have been powered to detect differences between subgroups. The study population may not fully represent the diversity of people with early-onset obesity, particularly those with genetic or syndromic causes."},{"rthcId":"RPEP-11162","title":"From Mechanism to Medicine: Peptide-Based Approaches for Cancer Diagnosis and Therapy.","authors":"Gouveia, Maria João; Campanhã, Joana; Barbosa, Francisca; Vale, Nuno","year":2025,"journal":"Biomolecules, 16(1)","doi":"10.3390/biom16010027","pmid":"41594569","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11163","title":"Probing non-peptide agonists binding at the human nociceptin/orphanin FQ receptor: a molecular modelling study.","authors":"Gozzi, Matteo; Malfacini, Davide; Albanese, Valentina; Pacifico, Salvatore; Preti, Delia; Guerrini, Remo; Calò, Girolamo; Ciancetta, Antonella","year":2025,"journal":"RSC medicinal chemistry, 16(4), 1584-1599","doi":"10.1039/d4md00747f","pmid":"39790123","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11164","title":"Role of interplay between endocannabinoids and neuropeptides in pathogenesis and therapy of depressive and anxiety disorders.","authors":"Gołyszny, Miłosz; Dragon, Jonasz; Obuchowicz, Ewa","year":2025,"journal":"Neuropeptides, 114, 102564","doi":"10.1016/j.npep.2025.102564","pmid":"41101142","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11165","title":"'This Is My Decision': A Qualitative Study of Individuals' Perspectives on Use of Semaglutide for Weight Loss.","authors":"Graabæk, Trine; Nguyen, Nini Thi; Sørensen, Malene Svoldgaard; Lundby, Carina","year":2025,"journal":"Basic & clinical pharmacology & toxicology, 137(1), e70069","doi":"10.1111/bcpt.70069","pmid":"40521912","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11166","title":"Novel cationic peptide OB1111 is a dual anti-planktonic and anti-biofilm agent against P. aeruginosa strains PA14 and PAO1.","authors":"Grace, Amber; Forte, Othreniel; Sipowe, Aguy; Tadjuidje, Vanella; Sahu, Rajnish; Owen, Donald R; Dennis, Vida A","year":2025,"journal":"BMC microbiology, 26(1), 49","doi":"10.1186/s12866-025-04599-9","pmid":"41398219","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"OB1111 demonstrated triple-action activity against P. aeruginosa strains PA14 (highly virulent) and PAO1 (moderately virulent):\n\n- Anti-planktonic: Effective inhibitory and bactericidal activity against both strains under standard testing conditions\n- Anti-biofilm: Killed bacteria within biofilms; reduced early biofilm attachment at sublethal concentrations\n- Anti-virulence: Reduced pyoverdine production (a key virulence factor) under host-mimicking conditions at sublethal doses\n- SEM showed membrane deformation and disintegration in both planktonic and biofilm states\n- PAO1 biofilms showed somewhat reduced susceptibility compared to PA14 biofilms at sublethal concentrations\n- Sublethal doses gradually reduced planktonic growth but showed less efficacy against established biofilms","whyItMatters":"P. aeruginosa is classified as a critical-priority pathogen by the WHO due to its multi-drug resistance. Traditional antibiotics typically only kill free-floating bacteria, leaving biofilm-protected populations intact to cause recurring infections. A peptide that simultaneously kills bacteria, disrupts biofilms, and reduces virulence could represent a more comprehensive treatment approach.","specificNumbers":"","methodology":"OB1111 was tested against P. aeruginosa PA14 and PAO1 under standard antimicrobial susceptibility testing (AST) and host-mimicking conditions. Both planktonic and biofilm states were evaluated at lethal and sublethal concentrations. Pyoverdine production and early biofilm attachment were measured. Scanning electron microscopy (SEM) visualized membrane damage.","limitations":"Only two reference laboratory strains were tested — clinical isolates may show different susceptibility profiles. The study was entirely in vitro; no animal infection models were used. Specific mechanisms of action beyond membrane disruption were not fully characterized. Peptide toxicity to human cells was not reported. Manufacturing scalability and stability were not addressed."},{"rthcId":"RPEP-11167","title":"Top 20 Research Studies of 2024 for Primary Care Physicians.","authors":"Grad, Roland; Ebell, Mark H","year":2025,"journal":"American family physician, 112(1), 34-41","doi":null,"pmid":"40736492","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11168","title":"Development of New Antimicrobial Peptides by Directional Selection.","authors":"Grafskaia, Ekaterina; Bobrovsky, Pavel; Kharlampieva, Daria; Brovina, Ksenia; Serebrennikova, Maria; Alieva, Sabina; Selezneva, Oksana; Bessonova, Ekaterina; Lazarev, Vassili; Manuvera, Valentin","year":2025,"journal":"Antibiotics (Basel, Switzerland), 14(11)","doi":"10.3390/antibiotics14111120","pmid":"41301615","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11169","title":"Additive Benefits of Control-IQ+ AID to GLP-1 Receptor Agonist Use in Adults With Type 2 Diabetes.","authors":"Graham, Timothy E; Raghinaru, Dan; Afreen, Samina; Ahmann, Andrew; Haidar, Ahmad; Raskin, Philip; Tsoukas, Michael A; Lum, John W; Sasson-Katchalski, Ravid; Pinsker, Jordan E; Beck, Roy W","year":2025,"journal":"Diabetes care, 48(12), 2154-2159","doi":"10.2337/dc25-1753","pmid":"41264828","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 143 GLP-1 RA users in the 319-participant randomized trial:\n\n- HbA1c decreased 0.8% from baseline (8.0 ± 1.2%) with AID, representing a 0.5% improvement vs. CGM group (95% CI: -0.8 to -0.3, p < 0.001)\n- Time-in-range (70-180 mg/dL) and hyperglycemia metrics showed statistically significant improvements\n- No significant weight difference with AID vs. CGM in GLP-1 users (+0.9 kg, 95% CI: -0.2 to 2.1, p = 0.10)\n- In contrast, GLP-1 non-users gained 1.9 kg with AID vs. CGM (95% CI: 0.5 to 3.2, p = 0.007)\n- Insulin use was simultaneously reduced alongside glycemic improvements\n\nThe combination of improved blood sugar control, reduced insulin requirements, and weight neutrality demonstrates clear additive benefits of combining AID with GLP-1 therapy.","whyItMatters":"This is the first randomized trial evidence showing that automated insulin delivery provides meaningful additional benefits even for patients already on optimal GLP-1 therapy — the current gold standard of diabetes treatment. The weight neutrality finding is particularly important: insulin therapy typically causes weight gain, which undermines metabolic benefits. By showing that GLP-1 drugs prevent this AID-associated weight gain, the study provides a strong rationale for combining these two technologies as complementary therapies.","specificNumbers":"","methodology":"This was a subgroup analysis from a randomized controlled trial comparing Control-IQ+ automated insulin delivery (AID) versus continuation of the pre-study insulin delivery method plus continuous glucose monitoring (CGM). Of 319 total participants with insulin-treated type 2 diabetes, 143 (45%) were using a GLP-1 RA at baseline and continued it during the 13-week trial. Outcomes included HbA1c change, CGM-derived glycemic metrics (time-in-range, hyperglycemia), insulin doses, and body weight.","limitations":"This is a subgroup analysis of a larger randomized trial, which reduces statistical power and may be subject to selection bias (GLP-1 use was not randomized). The 13-week duration is relatively short for assessing long-term glycemic and weight outcomes. Specific GLP-1 drugs and doses were not standardized across participants. The study population was insulin-treated type 2 diabetes, which represents a specific subset of all T2D patients. Cost and insurance coverage implications of combining AID technology with GLP-1 drugs were not addressed."},{"rthcId":"RPEP-11170","title":"Glucagon-like peptide-1 receptor agonists in liver transplant recipients with diabetes: changes in glucose control and cardiometabolic risk factors.","authors":"Grancini, Valeria; Cogliati, Irene; Alicandro, Gianfranco; Oliverio, Andreina; Di Benedetto, Clara; Gaglio, Alessia; Lampertico, Pietro; Resi, Veronica; Orsi, Emanuela","year":2025,"journal":"Frontiers in endocrinology, 16, 1586941","doi":"10.3389/fendo.2025.1586941","pmid":"40496570","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 68 liver transplant recipients with diabetes, GLP-1 receptor agonist therapy added to metformin or insulin significantly reduced fasting glucose, HbA1c, weight, BMI, waist circumference, and total/LDL cholesterol over 18 months. Liver stiffness decreased during the first 6 months. Among 45 patients on insulin at baseline, 33.2% stopped insulin by 6 months and 45.5% by 18 months. Adverse events were low: 26.9% mild nausea, 7.69% discontinued due to GI intolerance. No pancreatitis episodes occurred despite concurrent calcineurin inhibitors, and no immunosuppressant adjustments were needed.","whyItMatters":"Liver transplant recipients frequently develop diabetes (post-transplant diabetes or worsening pre-existing diabetes), but clinicians have been reluctant to use GLP-1 receptor agonists in these patients due to lack of safety data — particularly concerns about pancreatitis risk when combined with immunosuppressive drugs like calcineurin inhibitors. This study provides the first substantial evidence that GLP-1 RAs are both safe and effective in this population, with no drug interactions and a remarkable rate of insulin discontinuation.","specificNumbers":"","methodology":"Prospective observational study of 68 liver transplant recipients with diabetes who started GLP-1 RA therapy added to metformin or insulin. Patients were evaluated at baseline and at 6, 12, and 18 months. Assessments included glycemic control (fasting glucose, HbA1c), body composition (weight, BMI, waist circumference via bio-impedance analysis), liver health (stiffness and steatosis via transient elastography), pancreatic safety (amylase, lipase), and adverse event reporting via email contact.","limitations":"This is an observational study without a control group, so improvements cannot be definitively attributed to GLP-1 RA therapy alone. The 68-patient sample is relatively small. Follow-up of 18 months is insufficient to assess long-term complications. The specific GLP-1 RA agents and doses used are not detailed in the abstract. The study did not assess hard outcomes like cardiovascular events, renal impairment, or mortality."},{"rthcId":"RPEP-11171","title":"Preoperative weight loss by noninvasive approach in patients with obesity scheduled for bariatric and metabolic surgery: an update narrative review of indications and results available until 2024.","authors":"Grandone, Ilenia; Nannipieri, Monica; Conte, Caterina; Cava, Edda; Schiavo, Luigi","year":2025,"journal":"Updates in surgery, 77(7), 1985-1999","doi":"10.1007/s13304-025-02198-x","pmid":"40220081","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11172","title":"Semaglutide-induced Wernicke encephalopathy: a comprehensive analysis.","authors":"Gras, Cécile; De Wit, Victoria; Oussedik, Nacima; Daclin, Sylvie; Bourdin, Venceslas; Callot, Delphine; Chegrani, Ghiles; Rives-Lange, Claire; Chouchana, Laurent","year":2025,"journal":"European journal of clinical nutrition, 79(11), 1160-1163","doi":"10.1038/s41430-025-01653-7","pmid":"40908328","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11173","title":"GLP-1 receptor agonist therapy for obesity via direct-to-consumer telemedicine: Clinical characteristics and treatment outcomes.","authors":"Gratzke, Monika; von Bueren, Johannes; Garrahy, Edward; Calewaert, Bart; Abeck, Finn; Wuelfing, Christian","year":2025,"journal":"Digital health, 11, 20552076251382040","doi":"10.1177/20552076251382040","pmid":"41000573","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 966 patients prescribed liraglutide via a DTC telemedicine platform:\n\n- 85.6% reported weight loss >2 kg after 50 days, with an average loss of 4.9 kg\n- 94.1% adhered to the prescribed regimen\n- 39.8% reported adverse events, primarily gastrointestinal\n- 86.4% expressed desire to continue treatment despite side effects\n- 46.6% had a baseline BMI between 30 and 34.4 kg/m²\n- 88.9% were GLP-1 RA-naive (first time using these drugs)\n- 70% had long-standing obesity","whyItMatters":"The explosion of GLP-1 drug demand has outpaced traditional healthcare access, driving many patients to telemedicine platforms. This study provides some of the first real-world data on whether DTC prescribing of GLP-1 agonists produces meaningful results. The high adherence and weight loss rates suggest telemedicine can be an effective channel, though the lack of in-person monitoring raises safety questions that need longer-term study.","specificNumbers":"","methodology":"Retrospective cross-sectional study using anonymized data from 966 patients who received liraglutide prescriptions through a DTC telemedicine platform between August 2022 and April 2024. Patients completed an initial online eligibility questionnaire reviewed by a physician. A follow-up questionnaire at 50 days post-prescription assessed weight loss, adverse events, treatment adherence, and satisfaction using patient-reported outcomes.","limitations":"This is a retrospective study relying entirely on patient-reported outcomes without clinical verification (no measured weights, lab tests, or physical exams). The 50-day follow-up is very short and does not capture long-term efficacy, weight regain, or late adverse events. There was no control group. Patients using DTC platforms may differ from the general obese population in motivation and health literacy. The data comes from a single telemedicine platform."},{"rthcId":"RPEP-11174","title":"Relevance of Glucagon-Like Peptide 1 (GLP-1) in Inflammatory Bowel Diseases: A Narrative Review.","authors":"Gravina, Antonietta Gerarda; Pellegrino, Raffaele; Izzo, Michele; De Costanzo, Ilaria; Imperio, Giuseppe; Landa, Fabio; Tambaro, Assunta; Federico, Alessandro","year":2025,"journal":"Current issues in molecular biology, 47(5)","doi":"10.3390/cimb47050383","pmid":"40699782","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 receptor agonists appear to reduce the intestinal inflammatory burden through two main mechanisms: enhancing intestinal epithelial barrier function (the gut lining's ability to keep harmful substances out) and modulating the gut microbiota composition.\n\nThe review also addresses practical considerations including the safety profile of GLP-1 RAs in IBD patients, their impact on bowel preparation for endoscopic procedures (colonoscopies), and their effectiveness for managing the metabolic comorbidities (obesity, diabetes) that commonly accompany IBD. However, the evidence base consists primarily of preclinical studies and early clinical observations rather than definitive trials.","whyItMatters":"IBD affects millions of people worldwide and current treatments often have significant side effects or lose effectiveness over time. If GLP-1 drugs — which are already widely available and well-characterized for safety — could also help manage gut inflammation, this would represent a major advance. Many IBD patients also have obesity or diabetes, making GLP-1 RAs particularly attractive as they could potentially address multiple conditions simultaneously.","specificNumbers":"","methodology":"This is a narrative review that synthesized existing literature on GLP-1 biology, GLP-1 receptor agonist pharmacology, and their potential roles in inflammatory bowel disease. The review covered preclinical studies (animal and cell models) and early clinical observations, examining both the anti-inflammatory mechanisms and practical clinical considerations.","limitations":"As a narrative review, the evidence selection may not be as systematic or unbiased as a formal systematic review. The supporting evidence comes primarily from preclinical studies and early clinical observations rather than randomized controlled trials. The review does not provide quantitative data on the magnitude of anti-inflammatory effects. Long-term safety of GLP-1 RAs specifically in IBD populations has not been established."},{"rthcId":"RPEP-11175","title":"Raised intracranial pressure alters cortical vascular function and cephalic allodynia.","authors":"Grech, Olivia; Rubio-Beltran, Eloisa; Stanyer, Emily C; Labastida-Ramirez, Alejandro; Lavery, Gareth G; Hill, Lisa J; Holland, Philip R; Sinclair, Alexandra J","year":2025,"journal":"Brain : a journal of neurology, 148(6), 2163-2177","doi":"10.1093/brain/awae415","pmid":"40056451","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11176","title":"Phase 1 Study of AAV9.LAMP2B Gene Therapy in Danon Disease.","authors":"Greenberg, Barry; Taylor, Matthew; Adler, Eric; Colan, Steven; Ricks, David; Yarabe, Paul; Battiprolu, Pavan; Shah, Gaurav; Patel, Kinnari; Coggins, Matthew; Carou-Keenan, Susanna; Schwartz, Jonathan D; Rossano, Joseph W","year":2025,"journal":"The New England journal of medicine, 392(10), 972-983","doi":"10.1056/NEJMoa2412392","pmid":"39556016","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11177","title":"Evidence-based review and frontiers of migraine therapy.","authors":"Greene, Kaitlin A; Gelfand, Amy A; Larry Charleston","year":2025,"journal":"Neurogastroenterology and motility, 37(3), e14899","doi":"10.1111/nmo.14899","pmid":"39133210","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11178","title":"Semaglutide improved sperm morphology in obese men with type 2 diabetes mellitus and functional hypogonadism.","authors":"Gregorič, Nadan; Šikonja, Jaka; Janež, Andrej; Jensterle, Mojca","year":2025,"journal":"Diabetes, obesity & metabolism, 27(2), 519-528","doi":"10.1111/dom.16042","pmid":"39511836","tags":[],"studyType":"Randomized Open-Label Trial","evidenceStrength":"Moderate","keyFinding":"Semaglutide significantly improved sperm morphology in obese men with type 2 diabetes and functional hypogonadism, while testosterone replacement therapy (TRT) significantly decreased sperm concentration and total count.\n\nIn the semaglutide group, morphologically normal sperm doubled from 2% to 4% (p=0.012). Compared to TRT, the semaglutide group had significantly higher normal sperm count, sperm concentration, and total sperm number after 24 weeks. Both treatments increased total testosterone and improved hypogonadism symptoms, but only TRT improved erectile function scores.","whyItMatters":"Men with obesity and type 2 diabetes frequently develop functional hypogonadism — low testosterone driven by excess weight rather than testicular failure. Testosterone replacement therapy is standard treatment but suppresses sperm production, creating a dilemma for men who want to preserve fertility. This study suggests semaglutide could address both the hypogonadism symptoms and fertility simultaneously — a significant advantage over TRT for men planning families.","specificNumbers":"n=25 · 24 weeks · Semaglutide 1mg/week vs TRT 1000mg/10-12 weeks · Normal sperm: 2% → 4% (p=0.012) with semaglutide · Median age 50 · BMI 35.9 · Baseline sperm below 5th percentile","methodology":"Twenty-five men with type 2 diabetes, obesity (median BMI 35.9), and functional hypogonadism were randomized to receive either semaglutide 1 mg/week subcutaneously or intramuscular testosterone undecanoate 1000 mg every 10-12 weeks for 24 weeks. Semen analysis and hypogonadism parameters were measured at baseline and 24 weeks. Erectile function and aging symptoms were assessed via validated questionnaires (IIEF-15 and AMS).","limitations":"Small sample size of only 25 men limits statistical power and generalizability. The open-label design means neither participants nor investigators were blinded to treatment, introducing potential bias. The 24-week duration may not capture the full spermatogenesis cycle effects. Baseline sperm quality was very poor (below 5th percentile), so results may not apply to men with normal baseline fertility."},{"rthcId":"RPEP-11179","title":"Ciprofloxacin Inhibits Angiotensin I‑Converting Enzyme (ACE) Activity by Binding at the Exosite, Distal to the Catalytic Pocket.","authors":"Gregory, Kyle S; Ramasamy, Vinasha; Sturrock, Edward D; Acharya, K Ravi","year":2025,"journal":"ACS bio & med chem Au, 5(5), 852-859","doi":"10.1021/acsbiomedchemau.5c00089","pmid":"41112194","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11180","title":"Fatal, Fulminant, Necrotizing Pancreatitis Associated With Recent Tirzepatide Initiation.","authors":"Grennan, Krista; Borg, Courtney; Meneley, Ashley; Janitz, Tyler; Shuman, Midiia; Venegas, Carla","year":2025,"journal":"JCEM case reports, 3(6), luaf087","doi":"10.1210/jcemcr/luaf087","pmid":"40270999","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11181","title":"Hypokalemia Requiring Hospitalization After Taking Semaglutide Injections.","authors":"Grennan, Krista N; Singh, Devina; Chindris, Ana-Maria; Wilson, Jessica R","year":2025,"journal":"Cureus, 17(7), e87382","doi":"10.7759/cureus.87382","pmid":"40772190","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11182","title":"Diabetes Mellitus and Atrial Fibrillation: Mechanistic Insights and Therapeutic Impacts of Glucose-Lowering Drugs.","authors":"Grigore, Mihai; Grigore, Andreea-Maria; Ruxandra-Elena, Martin-Graur; Ioana, Verde; Uscoiu, Gabriela; Nicolae, Camelia; Balahura, Ana-Maria; Ilieșiu, Adriana-Mihaela","year":2025,"journal":"Life (Basel, Switzerland), 16(1)","doi":"10.3390/life16010016","pmid":"41598171","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11183","title":"Metabolic Remodeling and Mitochondrial Stress in Atrial Fibrillation: Mechanisms and Translational Targets.","authors":"Grigoriou, Konstantinos; Karakasis, Paschalis; Theofilis, Panagiotis; Vlachakis, Panayiotis K; Milaras, Nikias; Patoulias, Dimitrios; Antoniadis, Antonios P; Fragakis, Nikolaos","year":2025,"journal":"Reviews in cardiovascular medicine, 26(12), 44688","doi":"10.31083/RCM44688","pmid":"41524040","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11184","title":"Investigation of new non-toxic inhibitors of fibril formation and preservatives for insulin preparations its analogues.","authors":"Grishin, Sergei Y; Surin, Alexey K; Galzitskaya, Oxana V","year":2025,"journal":"Advances in protein chemistry and structural biology, 145, 113-143","doi":"10.1016/bs.apcsb.2024.09.013","pmid":"40324845","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11185","title":"The spontaneous neoantigen-specific CD4+ T cell response to a growing tumor is functionally and phenotypically diverse.","authors":"Griswold, Ryan Q; Brightman, Spencer E; Zavala, Karla Soria; Ordaz-Arias, Manuel Azaid; Djassemi, Navid; Thota, Rukman R; Naradikian, Martin S; Dose, Hannah; Alarcon, Suzie; Pandurangan, Vijayanand; Peters, Bjoern; Miller, Aaron M; Cohen, Ezra E W; Schoenberger, Stephen P","year":2025,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2025.03.25.645281","pmid":"40196575","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11186","title":"Exploring the Role of GLP-1 Agents in Managing Diabetic Foot Ulcers: A Narrative and Systematic Review.","authors":"Gruzmark, Fiona S; Beraja, Gabriela E; Jozic, Ivan; Lev-Tov, Hadar A","year":2025,"journal":"Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society, 33(5), e70085","doi":"10.1111/wrr.70085","pmid":"40888511","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11187","title":"Potential Implications of Body Mass Composition Changes in Heart Failure Patients in the Era of SGLT2i, GLP-1 RA, and GIP/GLP-1 RA.","authors":"Gryglewska-Wawrzak, Katarzyna; Kapłon-Cieślicka, Agnieszka; Pawlak, Agnieszka; Tomaszuk-Kazberuk, Anna; Rubiś, Paweł; Niedziela, Jacek; Bielecka-Dąbrowa, Agata","year":2025,"journal":"Pharmaceuticals (Basel, Switzerland), 18(11)","doi":"10.3390/ph18111726","pmid":"41304969","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11188","title":"Directed evolution-based discovery of ligands for in vivo restimulation of chimeric antigen receptor T cells.","authors":"Grzywa, Tomasz M; Neeser, Alexandra; Ramasubramanian, Ranjani; Romanov, Anna; Tannir, Ryan; Mehta, Naveen K; Cossette, Benjamin; Morgan, Duncan M; Goncalves, Beatriz; Sukaj, Ina; Bergaggio, Elisa; Kadauke, Stephan; Myers, Regina M; Paruzzo, Luca; Ghilardi, Guido; Cozzone, Austin; Schuster, Stephen J; Frey, Noelle; Zhang, Libin; Yousefpour, Parisa; Abraham, Wuhbet; Suh, Heikyung; Ruella, Marco; Grupp, Stephan A; Chiarle, Roberto; Wittrup, K Dane; Ma, Leyuan; Irvine, Darrell J","year":2025,"journal":"Nature biomedical engineering","doi":"10.1038/s41551-025-01470-0","pmid":"40855124","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Using yeast surface display and directed evolution, the team identified and optimized peptide mimotopes that bind to FMC63 — the antibody fragment used in clinical CD19 CAR-T products. These peptides were coupled to a lymph node-targeting amphiphilic PEG-lipid carrier (amph-vax) to create a vaccine-like booster.\n\nIn both syngeneic and humanized mouse models of B-acute lymphoblastic leukemia/lymphoma, the optimized amph-vax boosters triggered marked expansion and memory development of CD19 CAR-T cells. Mice receiving the peptide vaccine booster showed enhanced control of disease progression compared to those treated with CAR-T cells alone. The approach is designed to be generalizable to any CAR-T cell product.","whyItMatters":"CAR-T cell therapy has transformed treatment for certain blood cancers, but relapse remains a major challenge — often because the engineered T cells lose steam. A simple peptide-based vaccine booster that can be given after CAR-T infusion to recharge these cells could dramatically improve long-term outcomes. Importantly, this approach is designed to work with any CAR-T product, not just one specific therapy.","specificNumbers":"","methodology":"The researchers used yeast surface display — a technique where billions of peptide variants are displayed on yeast cells — to screen for peptides that bind to the FMC63 antibody fragment used in approved CD19 CAR-T products. The best candidates were then further improved through directed evolution (iterative rounds of mutation and selection). The optimized peptides were linked to an amphiphilic PEG-lipid carrier that targets lymph nodes. Efficacy was tested in syngeneic and humanized mouse models of B-ALL/lymphoma.","limitations":"All efficacy data comes from mouse models (syngeneic and humanized), which do not fully replicate the human immune environment or tumor complexity. The study focused on CD19-targeting CARs; while the authors state the approach is generalizable, this has not yet been demonstrated for other CAR targets. No human clinical data is available yet. The long-term durability of the boosting effect and potential for immune-related side effects need further study."},{"rthcId":"RPEP-11189","title":"Efficacy of thymosin α1 for sepsis: a systematic review and meta-analysis of randomized controlled trials.","authors":"Gu, Bin; Zhou, Yu; Nie, Yao; Wang, Luhao; Liang, Liqun; Liao, Zihuai; Wen, Jingyi; Guan, Xiangdong; Chen, Minying; Wu, Jianfeng; Pei, Fei","year":2025,"journal":"Frontiers in cellular and infection microbiology, 15, 1673959","doi":"10.3389/fcimb.2025.1673959","pmid":"40969554","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11190","title":"Association of semaglutide with retained gastric contents on endoscopy: Retrospective analysis.","authors":"Gu, Garrick Han; Pauplis, Connor; Seacor, Taylor; Devuni, Deepika; Krishnarao, Anita","year":2025,"journal":"Endoscopy international open, 13, a25501468","doi":"10.1055/a-2550-1468","pmid":"40230563","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11191","title":"Synergistic Anti-Helicobacter pylori Effects of Takifugu obscurus Skin Peptides and Lactobacillus plantarum: A Potential Gastric Health Dietary Supplement.","authors":"Gu, Lei; Tang, Yiying; Zhang, Jieshuai; Tao, Ningping; Wang, Xichang; Wang, Liping; Xu, Changhua","year":2025,"journal":"Foods (Basel, Switzerland), 14(3)","doi":"10.3390/foods14030406","pmid":"39941995","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11192","title":"Magnesium-Free Assembly of Cationic Peptide/DNA Nanostructures with Defined Geometries for Anticancer Drug Delivery.","authors":"Gu, Peng-Cheng; Chen, Chun-Fa; Ma, Lian-Ju; Wang, Lu; Bai, Yan; Yang, Jia-Qi; Zhu, Shu; Li, Quan; Bai, Jia-Hao; Sun, Yang-Yi; Chen, Xin-Hong; Jiang, Xin-Ya; Liu, Qian; Qian, Hang","year":2025,"journal":"ACS applied materials & interfaces, 17(27), 38971-38984","doi":"10.1021/acsami.5c07816","pmid":"40560802","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"RGD-TAT peptides replaced conventional magnesium ions for DNA nanostructure self-assembly while adding cancer targeting and cell penetration capabilities. The peptide/DNA nanostructures demonstrated high membrane penetration, integrin-mediated cancer cell targeting, and lysosome escape. Using protease-resistant D-type peptides significantly enhanced structural and serum stability.\n\nIn a mouse tumor model, the NTD-RGD-TAT-DOX-siKRAS nanotube showed excellent tumor accumulation and anti-cancer effects by simultaneously delivering doxorubicin and suppressing KRAS oncogene expression, combining chemotherapy with gene therapy in a single platform.","whyItMatters":"DNA nanotechnology has enormous potential for precision drug delivery, but instability and poor cell entry have limited clinical use. By replacing simple ions with functional peptides, this approach solves multiple problems simultaneously — the peptides both hold the structure together and actively target it to cancer cells. This could accelerate the translation of DNA nanomedicine to the clinic.","specificNumbers":"","methodology":"Cationic peptides (RGD-TAT) were used to assemble DNA nanostructures without magnesium. In vitro studies assessed cellular uptake, membrane penetration, integrin targeting, and lysosome escape. Stability was tested with both L-type and protease-resistant D-type peptides. In vivo proof of concept used doxorubicin and KRAS siRNA-loaded nanotubes in an immunodeficient mouse tumor model to assess tumor accumulation and anti-cancer efficacy.","limitations":"The in vivo study used an immunodeficient mouse model, which doesn't capture immune system interactions. Long-term toxicity and biodistribution were not reported. The scalability of manufacturing peptide/DNA nanostructures for clinical use remains unclear. The specific tumor type and KRAS-dependent mechanism may not generalize to all cancers."},{"rthcId":"RPEP-11193","title":"Efficacy and safety of once-weekly semaglutide 2.4 mg for weight management in participants from China: A prespecified analysis of the STEP 7 randomized clinical trial.","authors":"Gu, Weijun; Lu, Yibing; Ye, Xinhua; Yuan, Guoyue; Liu, Dongmei; Shen, Zewei; Zu, Ning; Mu, Yiming","year":2025,"journal":"Diabetes, obesity & metabolism, 27(5), 2540-2551","doi":"10.1111/dom.16253","pmid":"40069849","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11194","title":"Yueju Pill Inhibits Apoptosis by Regulating the SCF/c-Kit/PI3K/AKT Signaling Pathway to Ameliorate Functional Dyspepsia.","authors":"Gu, Yaru; Biao, Yaning; Liu, Chenxu; Zhang, Yufang; Gao, Ya; Xue, Yucong; Zhang, Yixin","year":2025,"journal":"Combinatorial chemistry & high throughput screening","doi":"10.2174/0113862073344555241120103257","pmid":"39917923","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11195","title":"Computational exploration of global venoms for antimicrobial discovery with Venomics artificial intelligence.","authors":"Guan, Changge; Torres, Marcelo D T; Li, Sufen; de la Fuente-Nunez, Cesar","year":2025,"journal":"Nature communications, 16(1), 6446","doi":"10.1038/s41467-025-60051-6","pmid":"40645962","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11196","title":"Long-term efficacy and safety of tirzepatide in participants with type 2 diabetes with inadequate glycaemic control on metformin and/or sulfonylurea: Post-hoc analysis of SURPASS-4.","authors":"Guan, Haixia; Jiang, Hongwei; Yuan, Huijuan; Sun, Jie; Xu, Jiawei; Ji, Linong","year":2025,"journal":"Diabetes, obesity & metabolism, 27(11), 6480-6490","doi":"10.1111/dom.70047","pmid":"40926359","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11197","title":"Factors affecting patient outcomes in pulmonary artery thromboendarterectomy under deep hypothermic circulatory arrest and cardiopulmonary bypass support----a single center's experience.","authors":"Guan, Ming; Yang, Xiaofang; Fu, Lin; Zhao, Xueting; Hei, Feilong","year":2025,"journal":"BMC cardiovascular disorders, 25(1), 760","doi":"10.1186/s12872-025-05242-1","pmid":"41126083","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11198","title":"Anti-β2GPI/β2GPI complex promotes thrombosis by activating the P2Y2/MAPKs pathway to increase human neutrophil peptides.","authors":"Guan, Xin; Liu, Wen; Gao, Tianfeng; Jin, Wenying; Gao, Yueqiu; Tan, Huiyuan; Guo, Lujie; Zhang, Yanfen","year":2025,"journal":"PloS one, 20(5), e0322447","doi":"10.1371/journal.pone.0322447","pmid":"40403008","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11199","title":"Association between weight reduction achieved with tirzepatide and quality of life in adults with obesity: Results from the SURMOUNT-1 study.","authors":"Gudzune, Kimberly A; Stefanski, Adam; Cao, Dachuang; Mojdami, Donna; Wang, Fangyu; Ahmad, Nadia; Ling Poon, Jiat","year":2025,"journal":"Diabetes, obesity & metabolism, 27(2), 539-550","doi":"10.1111/dom.16046","pmid":"39497468","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11200","title":"Antioxidant Effects of SGLT2 Inhibitors on Cardiovascular-Kidney-Metabolic (CKM) Syndrome.","authors":"Guerrero-Mauvecin, Juan; Villar-Gómez, Natalia; Miño-Izquierdo, Lucia; Povo-Retana, Adrián; Ramos, Adrian M; Ruiz-Hurtado, Gema; Sanchez-Niño, Maria D; Ortiz, Alberto; Sanz, Ana B","year":2025,"journal":"Antioxidants (Basel, Switzerland), 14(6)","doi":"10.3390/antiox14060701","pmid":"40563333","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11201","title":"Substitution of a proline residue in the frog skin host-defense peptide, figainin-2PL by D-lysine generates an analog with potent activity against antibiotic-resistant ESKAPE pathogens.","authors":"Guilhaudis, Laure; Cunning, Taylor S; Delaney, Jack J; Ternan, Nigel G; Mechkarska, Milena; Attoub, Samir; Conlon, J Michael","year":2025,"journal":"Peptides, 192, 171430","doi":"10.1016/j.peptides.2025.171430","pmid":"40659163","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11202","title":"Achievement of HbA1c and weight targets in adults with type 2 diabetes on once weekly injectable glucagon-like peptide-1 receptor agonist therapy in UK primary care: A retrospective, real-world study.","authors":"Gulati, Kunal; Wijndaele, Katrien; Webb, Joanne; von Arx, Lill-Brith; Seif, Monica; Jennison, Thomas; Geneidat, Antonia; Wild, Rosie; Wood, Robert; Khunti, Kamlesh","year":2025,"journal":"Diabetes, obesity & metabolism, 27(4), 2086-2095","doi":"10.1111/dom.16201","pmid":"39840515","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11203","title":"Semaglutide, central retinal thickness and continuous glucose monitoring in persons with type 2 diabetes: A post-hoc analysis from a randomised trial.","authors":"Gullaksen, Søren; Vernstrøm, Liv; Sørensen, Steffen Skovgaard; Funck, Kristian Løkke; Petersen, Line; Bek, Toke; Poulsen, Per Løgstrup; Laugesen, Esben","year":2025,"journal":"Journal of diabetes and its complications, 39(6), 109039","doi":"10.1016/j.jdiacomp.2025.109039","pmid":"40239470","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 10 semaglutide-treated patients, central retinal thickness (CRT) increased approximately 1% (3.76 μm, 95% CI -0.32 to 7.85, P = 0.065) compared to placebo — borderline non-significant. When adjusted for Time in Range (TIR), this effect was further attenuated (P = 0.21), indicating the retinal change was explained by glycemic improvement rather than a direct semaglutide effect.\n\nAcross all four treatment groups (semaglutide, empagliflozin, combination, and placebo), increased TIR was independently associated with increased CRT (0.07 μm per unit increase, 95% CI 0.03–0.12, P = 0.002). This confirms that rapid glycemic improvement — by any mechanism — is the driver of early retinal thickness changes.","whyItMatters":"The SUSTAIN-6 trial raised a safety signal suggesting semaglutide might worsen diabetic retinopathy, creating concern among patients and prescribers. This study provides mechanistic reassurance: the retinal changes appear to be a well-known consequence of rapid blood sugar improvement (called 'early worsening'), not a unique semaglutide toxicity. This is important for millions of patients taking semaglutide for diabetes and obesity.","specificNumbers":"","methodology":"This post-hoc analysis drew from a 32-week randomized, placebo-controlled, partly open-label trial of 120 type 2 diabetes patients investigating semaglutide and empagliflozin effects on target organ damage. Forty participants (10 from each of 4 treatment arms) were included. Time in Range (3.9–10.0 mmol/L) was measured using continuous glucose monitoring over 7–8 days. Central retinal thickness was assessed using optical coherence tomography (OCT). Statistical analyses adjusted for TIR to separate drug-specific effects from glycemia-driven changes.","limitations":"This is a small post-hoc analysis with only 10 patients per group, severely limiting statistical power. The borderline non-significant retinal thickness increase (P = 0.065) in the semaglutide group means the study cannot definitively rule out a small drug-specific effect. The 32-week follow-up may not capture longer-term retinal changes. OCT measures retinal thickness but does not assess clinical retinopathy outcomes like visual acuity loss. The partly open-label design could introduce bias."},{"rthcId":"RPEP-11204","title":"Dual GIP/GLP1-RA, GCGR/GLP-1 RA and GLP1-RA for the Treatment of Metabolic Dysfunction-associated Steatotic Liver Disease with Type 2 Diabetes: A Systematic Review and Meta-analysis.","authors":"Gunawan, Burhan; Nugroho, Heri; Sibarani, Roy Panusuan","year":2025,"journal":"TouchREVIEWS in endocrinology, 21(2), 26-32","doi":"10.17925/EE.2025.21.2.5","pmid":"41246119","tags":[],"studyType":"systematic review and meta-analysis","evidenceStrength":"high","keyFinding":"This meta-analysis of 13 randomized controlled trials (1,552 patients) found that GLP-1 receptor agonists, dual GIP/GLP-1 receptor agonists, and GCGR/GLP-1 receptor agonists all significantly reversed liver fibrosis (OR 3.72, p<0.001) and reduced liver fat content (mean decrease of 18.9%, p<0.001) in people with type 2 diabetes and fatty liver disease. Critically, dual-agonist drugs outperformed single GLP-1 agonists: GIP/GLP-1 agonists (like tirzepatide) showed an OR of 28.90 and GCGR/GLP-1 agonists an OR of 35.31 for liver fat reduction, compared to 8.23 for single GLP-1 agonists alone.","whyItMatters":"Metabolic dysfunction-associated steatotic liver disease (MASLD, formerly NAFLD) affects roughly 30% of the global population and is the fastest-growing cause of liver transplant. Until recently, there were no approved pharmacological treatments for liver fibrosis from fatty liver disease. This meta-analysis shows that incretin-based therapies — especially dual-agonist drugs — can both reduce liver fat and reverse fibrosis, potentially preventing progression to cirrhosis and liver failure. The superiority of dual agonists over single GLP-1 drugs is particularly significant for treatment selection.","specificNumbers":"13 RCTs · n=1,552 · Fibrosis reversal OR 3.72 (p<0.001) · LFC reduction MD -18.9% (p<0.001) · GIP/GLP-1 OR 28.90 · GCGR/GLP-1 OR 35.31 · Single GLP-1 OR 8.23","methodology":"Systematic search of PubMed, Web of Science, Scopus, and Cochrane databases for randomized controlled trials examining GLP-1 agonists, dual GIP/GLP-1 agonists, or GCGR/GLP-1 agonists in patients with both type 2 diabetes and MASLD. Outcomes included liver fibrosis reversal and liver fat content measured by MRI. Random-effects meta-analysis calculated mean differences and odds ratios with 95% confidence intervals across 13 studies.","limitations":"The included studies likely had varying definitions of MASLD/fibrosis, different drug doses and durations, and heterogeneous patient populations. The comparison between dual and single agonists may be confounded by differences in study populations and follow-up periods. Most included trials were designed primarily for diabetes outcomes, with liver endpoints as secondary. The meta-analysis compares drug classes broadly rather than head-to-head comparisons of specific medications."},{"rthcId":"RPEP-11205","title":"Semaglutide in Obesity and Type 2 Diabetes Management: A Systematic Review of Clinical Outcomes.","authors":"Gundapaneni, Sri Ram Charan; Burri, Rithwik Goud; Kaku, Rohini; Mamytova, Aiturgan; Kondadasula, Poshitha; Tagaev, Tugolbai","year":2025,"journal":"Cureus, 17(2), e78555","doi":"10.7759/cureus.78555","pmid":"40062102","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11206","title":"Fasting and postprandial oxytocin and incretin dynamics in women with polycystic ovary syndrome and healthy controls.","authors":"Gunesli, Irmak; Ulug, Elif; Pinar, Aylin Acikgoz; Portakal, Oytun; Yildiz, Bulent O","year":2025,"journal":"European journal of endocrinology, 193(2), 255-261","doi":"10.1093/ejendo/lvaf154","pmid":"40738489","tags":["glp-1-receptor-agonists","oxytocin","incretins"],"studyType":"cross-sectional","evidenceStrength":"moderate","keyFinding":"Women with PCOS had significantly lower fasting oxytocin levels (1294 vs 1580 pg/mL, p=0.024) and reduced baseline and postprandial GLP-1 and GIP levels compared to matched controls. Oxytocin and GLP-1 were correlated at all time points, and in healthy controls, early oxytocin changes correlated with hunger and satiety — a relationship absent in women with PCOS. Food cravings were also significantly higher in the PCOS group.","whyItMatters":"PCOS affects up to 10% of women and is often accompanied by weight gain and difficulty managing appetite. This study reveals that both oxytocin and incretin hormones are simultaneously disrupted in PCOS, suggesting a shared pathway that could explain the increased food cravings and appetite dysregulation these women experience.","specificNumbers":"n=72 (36 PCOS, 36 controls) · Oxytocin 1294 vs 1580 pg/mL (p=0.024) · GLP-1 baseline p<0.001 · GIP baseline p<0.001 · FCQ scores higher in PCOS (p<0.001)","methodology":"Cross-sectional study comparing 36 women with PCOS to 36 age- and BMI-matched healthy controls. All underwent a mixed meal test during the early follicular phase with blood drawn at 0, 30, 60, and 120 minutes. Measured oxytocin, GLP-1, and GIP levels. Hunger, satiety, and food cravings assessed using visual analog scales and the Food Craving Questionnaire.","limitations":"Cross-sectional design cannot establish causation. Moderate sample size of 72 total participants. Only studied during early follicular phase, so hormonal dynamics at other cycle points are unknown. Did not test whether correcting these peptide deficits would improve appetite symptoms."},{"rthcId":"RPEP-11207","title":"Mechanistic Design of Cell-Penetrating Disruptors for a Phospho-Dependent Interaction.","authors":"Gunning, Vanda; Batchelor, Matthew; Alexander, Krista K; Walko, Martin; Burgess, Selena G; Royle, Stephen J; Kennedy, Eileen J; Bayliss, Richard","year":2025,"journal":"Research square","doi":"10.21203/rs.3.rs-6862805/v1","pmid":"40585227","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11208","title":"An integrated multimodal approach to drug repurposing in endometriosis, using ROR1 as a target.","authors":"Gunther, Kate; Liu, Dongli; Stannard, Gill; Holmes, Melissa; Loo, Christine; Guo, Belinda; Bowden, Nikola; Abbott, Jason; Ford, Caroline E","year":2025,"journal":"Frontiers in pharmacology, 16, 1716062","doi":"10.3389/fphar.2025.1716062","pmid":"41415567","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"ROR1 was found to be transcriptionally upregulated and overexpressed at the protein level across endometriosis lesions in a dataset of 408 endometriosis samples and 53 controls, validated in 179 tissue microarray samples.\n\nOf three shortlisted compounds (rimegepant, cabergoline, pirenzepine), only rimegepant — a clinically approved CGRP antagonist — significantly reduced viability in 12Z endometriotic cells. In patient-derived organoids from deep infiltrating endometriosis, two of three models showed concentration-dependent antiproliferative and cytotoxic effects with morphological features consistent with cell death, while one model was less responsive.","whyItMatters":"Endometriosis affects roughly 10% of reproductive-age women and current treatments are mostly hormonal with significant side effects. Finding that an already-approved, well-tolerated migraine drug targeting CGRP peptide signaling could inhibit endometriosis growth opens a faster path to clinical testing than developing a new drug from scratch. This is among the first evidence connecting CGRP antagonism to endometriosis treatment.","specificNumbers":"","methodology":"Researchers first analyzed ROR1 expression in transcriptomic datasets (408 endometriosis samples, 53 controls) and validated protein-level expression in tissue microarrays (179 tissues). They used the BLAZE computational platform to identify drugs predicted to bind ROR1, filtered for safety, and screened three candidates in the 12Z endometriotic cell line. The most promising compound, rimegepant, was further tested in three patient-derived organoid models representing deep infiltrating endometriosis.","limitations":"This is entirely preclinical with no human clinical data. Only three patient-derived organoid models were tested, and one did not respond, highlighting patient-specific variability. The study used an in vitro screening approach and has not demonstrated efficacy in animal models or humans. The mechanism by which rimegepant affects endometriosis cells (whether through ROR1, CGRP receptor, or another target) is not fully clarified. The concentrations used in lab models may not reflect achievable drug levels in human tissue."},{"rthcId":"RPEP-11209","title":"The Molecular Mechanism for the Interactions of Melittin Peptide with Hofmeister Anions at Air-Water Interfaces.","authors":"Gunwant, Vineet; Pandey, Ravindra","year":2025,"journal":"The journal of physical chemistry. B, 129(31), 7896-7904","doi":"10.1021/acs.jpcb.5c03152","pmid":"40616203","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11210","title":"Clinical application research of brain natriuretic peptide in patients with aneurysmal subarachnoid hemorrhage.","authors":"Guo, Aiying; Ye, Cuijie; Li, Jing; Cao, Wei","year":2025,"journal":"Medicine, 104(41), e44985","doi":"10.1097/MD.0000000000044985","pmid":"41088672","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11211","title":"Prepregnancy GLP-1RA use improves maternal lipid metabolism via liver-secreted FGF21 during pregnancy in HFD-fed dams.","authors":"Guo, Haonan; Jing, Yingyu; Zhang, Yifan; Song, Lin; Wu, Wenjing; Wang, Jingyue; Wang, Mengjun; Niu, Xinyi; Wang, Mingxi; Pan, Xingyan; Wang, Ting; Cui, Wei; Sun, Bo; Wang, Ning","year":2025,"journal":"Obesity (Silver Spring, Md.), 33(8), 1504-1517","doi":"10.1002/oby.24328","pmid":"40635195","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11212","title":"Comparative efficacy and safety of GLP-1 receptor agonists for weight reduction: A model-based meta-analysis of placebo-controlled trials.","authors":"Guo, Haoyang; Yang, Juan; Huang, Jihan; Xu, Ling; Lv, Yinghua; Wang, Yexuan; Ren, Jiyuan; Feng, Yulin; Zheng, Qingshan; Li, Lujin","year":2025,"journal":"Obesity pillars, 13, 100162","doi":"10.1016/j.obpill.2025.100162","pmid":"39980735","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 55 placebo-controlled trials of 12 GLP-1 receptor agonists in 16,269 participants, maximum weight reduction ranged from 4.25 kg (liraglutide) to 22.6 kg (retatrutide). At 52 weeks, the hierarchy was clear: mono-agonists averaged 7.03 kg, dual-agonists 11.07 kg, and tri-agonists 24.15 kg of weight loss.\n\nOnset times varied considerably: orforglipron showed effects fastest (6.4 weeks) while tirzepatide was slowest to plateau (19.5 weeks). Six drugs showed significant dose-response relationships. Age was negatively correlated with weight loss (younger patients lost more), while baseline weight and BMI had no significant impact on outcomes. GI adverse events (nausea, vomiting, diarrhea, constipation) were significantly more common than placebo, with nausea being the most frequent.","whyItMatters":"This is the most comprehensive head-to-head comparison of GLP-1 weight loss drugs to date, providing the quantitative data clinicians and patients need to make informed treatment decisions. The clear dose-response relationships and the dramatic superiority of multi-receptor agonists (dual and triple) suggest that the next generation of drugs will be substantially more effective — though the trade-off with GI side effects must be carefully managed.","specificNumbers":"","methodology":"Model-based meta-analysis of placebo-controlled randomized clinical trials identified through systematic review of public databases. Time-course, dose-response, and covariate models characterized efficacy across 12 GLP-1 receptor agonists. Subgroup analyses compared mono-, dual-, and tri-agonists. Meta-analyses compared adverse event incidence and dropout rates across drugs.","limitations":"The analysis compares drugs across separate trials rather than head-to-head RCTs, introducing potential confounders from differences in study populations and designs. Some newer drugs (retatrutide, orforglipron) have limited Phase III data. The model-based approach assumes certain mathematical relationships in dose-response and time-course that may not perfectly capture biological reality. Long-term safety and weight maintenance after drug discontinuation are not addressed."},{"rthcId":"RPEP-11213","title":"GLP-1 Receptor Agonists and Research to Treat Overeating and Substance Use Disorders.","authors":"Guo, Jingchuan; Hayes, Matthew R; Leggio, Lorenzo; Oru, Ena; Rinaman, Linda","year":2025,"journal":"The Journal of neuroscience : the official journal of the Society for Neuroscience, 45(46)","doi":"10.1523/JNEUROSCI.1375-25.2025","pmid":"41224657","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11214","title":"Clinical efficacy and safety of sodium-glucose cotransporter protein-2 (SGLT-2) inhibitor, glucagon-like peptide-1 (GLP-1) receptor agonist, and Finerenone in type 2 diabetes mellitus with non-dialysis chronic kidney disease: a network meta-analysis of randomized clinical trials.","authors":"Guo, Jingyi; Wei, Maoying; Zhang, Wenhua; Jiang, Yijia; Li, Aijing; Wang, Churan; Yin, Dan; Sun, Anning; Gong, Yanbing","year":2025,"journal":"Frontiers in pharmacology, 16, 1517272","doi":"10.3389/fphar.2025.1517272","pmid":"40213686","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 39 RCTs and 99,599 patients, each drug class showed distinct advantages:\n\n**SGLT-2 inhibitors** were superior for HbA1c reduction (MD -0.33), blood pressure lowering (systolic MD -5.52 to -1.50), and weight loss (MD -3.81 to -1.29 kg). Empagliflozin ranked highest for HbA1c and diastolic blood pressure reduction. Canagliflozin ranked best for systolic blood pressure and weight loss.\n\n**GLP-1 receptor agonists**: Liraglutide was the most effective agent for LDL cholesterol reduction (MD -1.58 to -1.41). Semaglutide was the least harmful to estimated GFR, an important consideration in kidney disease patients.\n\n**Finerenone** significantly reduced systolic blood pressure (MD -1.65) and had the lowest urinary tract infection rate.\n\nSafety profiles were generally favorable across all classes, with different drugs showing advantages for specific adverse events.","whyItMatters":"Diabetic kidney disease is one of the leading causes of kidney failure worldwide, and clinicians now have three powerful drug classes to choose from — but until this analysis, there was no comprehensive head-to-head comparison across all three. This network meta-analysis helps answer a critical clinical question: for a specific patient with diabetic kidney disease, which drug class offers the best combination of benefits and lowest risk?","specificNumbers":"","methodology":"This was a systematic review and network meta-analysis following PRISMA-NMA guidelines, registered on PROSPERO. Researchers searched seven databases through November 2023 for randomized controlled trials comparing SGLT-2 inhibitors, GLP-1 receptor agonists, and finerenone in type 2 diabetes patients with non-dialysis chronic kidney disease. They assessed bias using RoB 2.0, evidence confidence using CINeMA, and performed traditional and network meta-analyses with random-effects models. Surface under the cumulative ranking curve (SUCRA) scores ranked treatments.","limitations":"Network meta-analysis relies on indirect comparisons across trials with different designs, populations, and follow-up periods. The included studies varied in CKD stage, baseline characteristics, and drug dosing. Some specific drug comparisons had limited evidence. The analysis focused on surrogate outcomes (HbA1c, blood pressure, weight) rather than hard endpoints like kidney failure or death. Publication bias may affect results. The search was limited to November 2023, missing more recent trial data."},{"rthcId":"RPEP-11215","title":"Effect of Semaglutide on Atrial Arrhythmias Recurrence Following Ablation for Atrial Fibrillation: A Prospective Study.","authors":"Guo, Jiongchao; Song, Ziliang; Wang, Shiyi; Yao, Die; Hong, Yu; Fu, Minmin; Chen, Min; Jiang, Weifeng; Zhang, Yu; Wu, Shaohui; Liu, Xu; Hou, Xumin; Qin, Mu","year":2025,"journal":"Circulation. Arrhythmia and electrophysiology, 18(11), e014069","doi":"10.1161/CIRCEP.125.014069","pmid":"41064855","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11216","title":"Massa Medicata Fermentata treated spleen deficiency constipation by mediating intestinal microbiota and serum peptide.","authors":"Guo, Kangxiao; Tang, Yuan; Yang, Tao; Yan, Yongwang","year":2025,"journal":"Frontiers in cellular and infection microbiology, 15, 1556915","doi":"10.3389/fcimb.2025.1556915","pmid":"40115071","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11217","title":"Efficacy and safety of tirzepatide added to basal insulin in patients with type 2 diabetes in China (SURPASS-CN-INS): a double-blind, multicentre, randomised, placebo-controlled, phase 3 trial.","authors":"Guo, Lixin; Dong, Xiaolin; Ma, Jianhua; Liu, Ming; Lu, Yibing; Wang, Hongman; Li, Qingju; Li, Ling; Deng, Yuying; Xu, Jiawei","year":2025,"journal":"The lancet. Diabetes & endocrinology, 13(12), 1015-1029","doi":"10.1016/S2213-8587(25)00248-7","pmid":"41167231","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tirzepatide added to basal insulin produced significant HbA1c reductions at week 40:\n\n- Tirzepatide 10mg: -2.39% (SE 0.13) vs placebo -0.91% (SE 0.12); difference -1.48% (97.5% CI -1.87 to -1.08; p<0.0001)\n- Tirzepatide 15mg: -2.37% (SE 0.13) vs placebo -0.91%; difference -1.45% (97.5% CI -1.85 to -1.06; p<0.0001)\n- Tirzepatide 5mg also showed improvements (specific numbers not primary endpoint)\n\nThe most common adverse events were gastrointestinal: diarrhea (26-37% vs 8%), decreased appetite (25-32% vs 0%), nausea (5-11% vs 3%), and vomiting (6-9% vs 0%), predominantly mild or moderate.","whyItMatters":"China has the world's largest diabetes population (~140 million), and many patients remain inadequately controlled on basal insulin. This trial demonstrates that tirzepatide can be safely and effectively added to existing insulin therapy, providing a much-needed intensification option. The magnitude of HbA1c reduction (~1.5% beyond placebo) is clinically very significant and could prevent serious diabetic complications.","specificNumbers":"","methodology":"SURPASS-CN-INS was a 40-week, double-blind, multicentre, randomized, placebo-controlled phase 3 trial across 26 hospitals in China. 257 patients with uncontrolled type 2 diabetes on insulin glargine (± metformin ± SGLT2 inhibitor) were randomized 1:1:1:1 to weekly subcutaneous tirzepatide 5mg, 10mg, 15mg, or placebo. Randomization was stratified by baseline HbA1c and SGLT2 inhibitor use. The primary endpoint was HbA1c change from baseline to week 40.","limitations":"The sample size (257 patients) is relatively modest for a phase 3 trial. The 40-week duration may not capture long-term safety signals or durability of effect. The trial was conducted exclusively in Chinese patients, so results may not be fully generalizable to other populations. The study was funded by Eli Lilly, the manufacturer. GI side effects, while mostly mild, were substantially more frequent with tirzepatide than placebo."},{"rthcId":"RPEP-11218","title":"Mazdutide versus dulaglutide in Chinese adults with type 2 diabetes.","authors":"Guo, Lixin; Zhang, Bo; Xue, Xia; Zhang, Xin; Cai, Hanqing; Jiang, Hongwei; Zhang, Lili; Jin, Ping; Wang, Xiaojing; Cheng, Zhifeng; Zhang, Suhe; Geng, Jianlin; Guo, Yushan; Hu, Hanbo; Ma, Qingyang; Li, Li; Du, Haiwei; Han-Zhang, Han; Xue, Fengtai; Deng, Huan; Qian, Lei; Yang, Wenying","year":2025,"journal":"Nature","doi":"10.1038/s41586-025-10031-z","pmid":"41407860","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"731 participants with T2D were randomized 1:1:1 to 4 mg mazdutide, 6 mg mazdutide, or 1.5 mg dulaglutide for 28 weeks on background oral anti-diabetic drugs. Both mazdutide doses demonstrated non-inferiority AND superiority to dulaglutide for HbA1c change from baseline.\n\nHbA1c treatment differences: 4 mg mazdutide was -0.24% better than dulaglutide (p=0.0032); 6 mg mazdutide was -0.30% better (p=0.0003). Weight loss differences were even more dramatic: 4 mg mazdutide achieved 3.78% more body weight reduction, and 6 mg mazdutide achieved 5.76% more (both p<0.0001). Mazdutide was generally safe but had higher gastrointestinal adverse events than dulaglutide — consistent with its dual-receptor mechanism.","whyItMatters":"The GLP-1 market is dominated by Western pharmaceutical companies (Novo Nordisk's semaglutide, Eli Lilly's tirzepatide). Mazdutide, developed by the Chinese biotech company Innovent Biologics, represents a major Chinese entry into this space. Its dual GLP-1/glucagon mechanism is distinct from tirzepatide's dual GLP-1/GIP approach, offering potentially different clinical benefits. Publication in Nature — reserved for the most significant scientific findings — signals that the global scientific community views mazdutide as a serious advance.","specificNumbers":"","methodology":"Phase III, randomized, active-controlled clinical trial conducted in China. 731 adults with type 2 diabetes on background oral anti-diabetic drugs were randomized 1:1:1 to once-weekly subcutaneous 4 mg mazdutide, 6 mg mazdutide, or 1.5 mg dulaglutide for 28 weeks. The primary endpoint was mean change in HbA1c from baseline, with a non-inferiority margin of 0.3% and subsequent superiority testing. Secondary endpoints included body weight change. Safety was assessed throughout.","limitations":"The 28-week duration is relatively short for a chronic disease treatment. The study was conducted exclusively in Chinese adults, and results may differ in other populations due to genetic and metabolic differences. The comparator was dulaglutide 1.5 mg, which is not the most potent GLP-1 drug available (semaglutide and tirzepatide are more effective). Higher GI adverse events with mazdutide may limit tolerability in some patients. Long-term cardiovascular and safety outcomes were not assessed."},{"rthcId":"RPEP-11219","title":"Potentials of food-derived peptides as novel antihypertensive agents and their acting mechanisms.","authors":"Guo, Ru-Xue; Shen, Liang","year":2025,"journal":"Food chemistry, 494, 146183","doi":"10.1016/j.foodchem.2025.146183","pmid":"40907185","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11220","title":"Lingguizhugan Decoction improves chronic heart failure by synergistically modulating ?1-AR/Gs/GRKs/?-arrestin signaling bias.","authors":"Guo, Shuting; Xia, Lei; Yang, Songru; Liang, Yueyang; Shan, Xiaoli; Zhao, Pei; Guo, Wei; Zhang, Chen; Xu, Ming; Sun, Ning; Lu, Rong; Chen, Huihua","year":2025,"journal":"Chinese journal of natural medicines, 23(5), 560-571","doi":"10.1016/S1875-5364(25)60863-6","pmid":"40383612","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11221","title":"Semaglutide Alleviates Ovarian Oxidative Stress and Autophagy via the PI3K/AKT/mTOR Pathway in Mice with Polycystic Ovary Syndrome.","authors":"Guo, Sili; Li, Xiaohan; Liu, Mei; Feng, Meiqi; Wang, Xi; Xue, Haibo; Zhang, Lei","year":2025,"journal":"Drug design, development and therapy, 19, 4297-4310","doi":"10.2147/DDDT.S522730","pmid":"40433568","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11222","title":"Safety, dosimetry, and efficacy of an optimized long-acting somatostatin analog for peptide receptor radionuclide therapy in metastatic neuroendocrine tumors: From preclinical testing to first-in-human study.","authors":"Guo, Wei; Wen, Xuejun; Chen, Yuhang; Zhao, Tianzhi; Liu, Jia; Tao, Yucen; Fu, Hao; Wang, Hongjian; Xu, Weizhi; Pang, Yizhen; Zhao, Liang; Huang, Jingxiong; Xu, Pengfei; Guo, Zhide; Miao, Weibing; Zhang, Jingjing; Chen, Xiaoyuan; Chen, Haojun","year":2025,"journal":"Acta pharmaceutica Sinica. B, 15(2), 707-721","doi":"10.1016/j.apsb.2024.05.022","pmid":"40177560","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11223","title":"Boosting health: Candida phyllophila J14-4 fermentation enhances angiotensin-converting enzyme inhibition and antihypertensive properties in wheat wort.","authors":"Guo, Xing; Wang, Maomao; Cheng, Yifan; Hu, Zeyu; Yuan, Yahong; Yue, Tianli","year":2025,"journal":"Food chemistry, 495(Pt 3), 146533","doi":"10.1016/j.foodchem.2025.146533","pmid":"41033035","tags":[],"studyType":"animal","evidenceStrength":"preliminary","keyFinding":"Fermenting wheat with the yeast Candida phyllophila J14-4 increased angiotensin-converting enzyme (ACE) inhibition activity by 46.05%. Peptide components under 3 kDa in the fermented wheat showed strong ACE-inhibitory activity, with the most potent peptide reaching 93.23% inhibition. In spontaneously hypertensive rats, the antihypertensive effect of the fermented wheat was comparable to captopril, a standard prescription ACE inhibitor drug.","whyItMatters":"With hypertension affecting over 25% of adults globally, finding food-derived alternatives or complements to pharmaceutical ACE inhibitors is of great interest. This study shows that a simple fermentation process can generate bioactive peptides from wheat that rival a prescription drug's blood pressure-lowering effect in animal models — pointing toward functional foods as a hypertension management tool.","specificNumbers":"","methodology":"Researchers fermented wheat wort with Candida phyllophila J14-4 and measured ACE inhibition activity in vitro. The antihypertensive effect was tested in vivo using spontaneously hypertensive rats (SHR), with captopril as a positive control. Volatile compounds were characterized using GC-IMS, and peptide fractions were separated by molecular weight to identify the most active ACE-inhibitory components.","limitations":"This is an animal study in spontaneously hypertensive rats, which may not predict blood pressure effects in humans. The fermented wheat product is not standardized for clinical use. The specific peptide sequences responsible for ACE inhibition were not fully identified. Bioavailability of the peptides after oral consumption in humans is unknown."},{"rthcId":"RPEP-11224","title":"Sacubitril/valsartan affects pulmonary arterial pressure in heart failure with preserved ejection fraction and pulmonary hypertension among PD patients.","authors":"Guo, Yanhong; Zhao, Silu; Zhang, Xuewen; Gou, Rong; Wang, Liuwei; Wang, Yulin; Zhai, Zihan; Yu, Lu; Tang, Lin","year":2025,"journal":"International urology and nephrology, 57(11), 3879-3888","doi":"10.1007/s11255-025-04580-5","pmid":"40410560","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"After three months of sacubitril/valsartan treatment, median pulmonary artery pressure in peritoneal dialysis patients dropped from 48.00 mmHg to 33.00 mmHg (P<0.001).\n\nThe percentage reduction in pulmonary artery pressure was -30.0% with sacubitril/valsartan versus -8.6% with ARB alone (P<0.001) — more than three times greater.\n\nHeart failure biomarkers NT-proBNP (N-terminal B-type natriuretic peptide precursor) and cardiac troponin I were both significantly reduced after sacubitril/valsartan treatment. Left ventricular remodeling was also attenuated. Standard ARB therapy did not show significant advantages compared to sacubitril/valsartan on any of these measures.","whyItMatters":"Peritoneal dialysis patients with heart failure and pulmonary hypertension have very limited treatment options and high mortality. Sacubitril/valsartan works by inhibiting neprilysin — the enzyme that breaks down beneficial natriuretic peptides like BNP and ANP — effectively boosting the body's natural peptide-based cardiovascular protection system. This study provides the first evidence that this natriuretic peptide-enhancing strategy can meaningfully reduce pulmonary pressures in this vulnerable patient population.","specificNumbers":"","methodology":"Prospective comparative study with 145 peritoneal dialysis patients with heart failure with preserved ejection fraction (HFpEF) and pulmonary hypertension receiving sacubitril/valsartan, and 38 control patients treated with standard angiotensin receptor blocker (ARB). Patients were followed for 3 months. Efficacy was assessed through biochemical parameters (NT-proBNP, cardiac troponin I), echocardiographic indicators (pulmonary artery pressure, cardiac remodeling measures), and adverse reaction monitoring.","limitations":"The study is not randomized — patients were assigned to groups rather than randomized, introducing potential selection bias. The groups are significantly unbalanced (145 vs. 38 patients). Three months of follow-up is relatively short, and longer-term outcomes including mortality are not reported. The study is from a single center, limiting generalizability. Heart failure with preserved ejection fraction is a heterogeneous condition, and results may not apply to all HFpEF subtypes. Specific sacubitril/valsartan doses are not detailed in the abstract."},{"rthcId":"RPEP-11225","title":"Nanoparticulate delivery and targeting of RNA to the brain.","authors":"Gupta, Aditya; Ramanathan, Raghu; Raulji, Chittalsinh M; I Mahato, Ram","year":2025,"journal":"Biochimica et biophysica acta. Reviews on cancer, 1880(6), 189480","doi":"10.1016/j.bbcan.2025.189480","pmid":"41429715","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11226","title":"Optimizing the Use of N-terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) in the Diagnosis of Heart Failure With Preserved Ejection Fraction (HFpEF): A Clinical Pathway Approach to an Underdiagnosed Entity.","authors":"Gupta, Mukulesh; Kumar, Dinesh; Gupta, Tuhina","year":2025,"journal":"Cureus, 17(12), e99161","doi":"10.7759/cureus.99161","pmid":"41536407","tags":[],"studyType":"review","evidenceStrength":"review","keyFinding":"NT-proBNP is a widely used biomarker for heart failure, but its diagnostic accuracy in HFpEF (heart failure with preserved ejection fraction) is compromised by age, obesity, atrial fibrillation, and kidney dysfunction. This review proposes a structured clinical pathway that combines adjusted NT-proBNP thresholds, clinical scoring systems like the H2FPEF and HFA-PEFF scores, and multimodal imaging to improve diagnosis of this commonly missed condition.\n\nHFpEF accounts for approximately 50% of all heart failure cases globally but remains one of the most underdiagnosed cardiovascular conditions because its symptoms mimic those of other age-related conditions.","whyItMatters":"Half of all heart failure patients have HFpEF, yet many go undiagnosed because the standard biomarker (NT-proBNP) can be misleading in the very populations most affected — older adults with obesity, kidney problems, or irregular heart rhythms. A structured diagnostic approach could catch thousands of missed cases and connect patients to treatment earlier.","specificNumbers":"~50% of global HF cases are HFpEF · Evidence compiled from 2022-2025 · Confounders: age, obesity, atrial fibrillation, renal dysfunction","methodology":"Narrative review critically analyzing recent evidence from 2022-2025 on NT-proBNP's diagnostic role in HFpEF. The authors propose a stepwise clinical pathway integrating adjusted biomarker thresholds, validated scoring systems, and imaging modalities.","limitations":"As a narrative review published in Cureus (an open-access journal with lighter peer review), the evidence synthesis may not be as rigorous as a systematic review. The proposed clinical pathway has not been prospectively validated. The abstract doesn't detail how studies were selected or assessed for quality."},{"rthcId":"RPEP-11227","title":"Glucagon-Like Peptide-1 Receptor Agonists Reduce Surgeries and Hospitalizations in Hidradenitis Suppurativa: A Multicenter TriNetX Cohort Study.","authors":"Gupta, Neal; Zafar, Kayla; Patel, Paras; Kabakova, Margaret; Collins, Alexia; Ray, Maile; Shayya, Ashley; McGinnis, Sandra; Kurtti, Alana; Cohen, Marc; Austin, Evan; Derrick, Kristina; Glick, Sharon; Jagdeo, Jared","year":2025,"journal":"Journal of drugs in dermatology : JDD, 24(9), 869-874","doi":"10.36849/jdd.8926","pmid":"40911751","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11228","title":"Beyond Blood Sugar: A Scoping Review of GLP-1 Receptor Agonists in Cardiovascular Care.","authors":"Gupta, Neil; Zayyad, Zaid; Bhattaram, Rohan; Tiu, David; Dau, Jennifer; Guburxani, Vidur; Kalzuna, Stephanie Dwyer; Shroff, Adhir R","year":2025,"journal":"Cardiology and therapy, 14(3), 351-366","doi":"10.1007/s40119-025-00426-4","pmid":"40643886","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11229","title":"Optimising obesity management: integrating continuous glucose monitoring with GLP-1 receptor agonists.","authors":"Gupta, Pragati; Pozzilli, Paolo","year":2025,"journal":"Diabetes research and clinical practice, 228, 112434","doi":"10.1016/j.diabres.2025.112434","pmid":"40849048","tags":[],"studyType":"perspective","evidenceStrength":"very low","keyFinding":"This perspective proposes combining continuous glucose monitoring (CGM) with GLP-1 receptor agonists like semaglutide for personalized obesity management, even in people without diabetes. CGM provides real-time metabolic feedback that could help optimize GLP-1 therapy by tracking glucose variability and behavioral patterns, while GLP-1 drugs address appetite dysregulation and hyperinsulinemia. However, the authors acknowledge a critical evidence gap: no randomized controlled trials have assessed this combination specifically for obesity in non-diabetic populations. They also note that CGM-derived metrics remain unstandardized in this context and suggest that AI-driven CGM analysis could predict individual responsiveness to GLP-1 therapy.","whyItMatters":"CGM devices are increasingly being marketed directly to consumers for general wellness and weight management, even without diabetes. Simultaneously, GLP-1 drugs are being prescribed to millions of non-diabetic people for weight loss. The convergence of these two trends creates a natural question: could combining real-time glucose data with GLP-1 therapy produce better, more personalized obesity outcomes? This perspective frames the opportunity while honestly noting that evidence to support the combination doesn't yet exist.","specificNumbers":"0 RCTs of CGM + GLP-1 RA in non-diabetic obesity · CGM metrics unstandardized for obesity context","methodology":"This is a narrative perspective reviewing existing evidence on CGM technology, GLP-1 receptor agonist therapy, and the potential synergy between them for obesity management. It synthesizes current knowledge and identifies evidence gaps rather than presenting original data.","limitations":"This is an opinion/perspective piece with no original data. The proposed benefits of combining CGM with GLP-1 therapy are theoretical — no clinical trials have tested this approach. CGM metrics in non-diabetic populations lack established reference ranges and clinical significance thresholds. The cost-effectiveness of adding CGM to GLP-1 therapy is not addressed. The perspective doesn't discuss potential harms of CGM in non-diabetic populations, such as anxiety from glucose fluctuations that are actually normal."},{"rthcId":"RPEP-11230","title":"Structural insights into the binding modes of Arrestin-3 finger loop to the neuropeptide Y1 and Y2 receptors.","authors":"Gupta, Varsha; Laugwitz, Jeannette M; Sklodowski, Mateusz; Voitel, Matthias; Sala, Davide; Kaiser, Anette; Elgeti, Matthias; Meiler, Jens; Huster, Daniel; Beck-Sickinger, Annette G; Schmidt, Peter; Penk, Anja","year":2025,"journal":"Structure (London, England : 1993), 33(10), 1728-1738.e5","doi":"10.1016/j.str.2025.07.012","pmid":"40780192","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11231","title":"Successful Use of Glucagon-Like Peptide-1 Receptor Agonist in a Patient With Recurrent Hypertriglyceridemia-Induced Pancreatitis.","authors":"Guralwar, Chinmay; Mitsuhashi, Shuji; Ashkar, Motaz; Chedid, Victor G","year":2025,"journal":"ACG case reports journal, 12(11), e01890","doi":"10.14309/crj.0000000000001890","pmid":"41267906","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A 42-year-old woman with recurrent hypertriglyceridemia-induced acute pancreatitis was started on a GLP-1 receptor agonist despite the conventional concern about pancreatitis risk with this drug class. The outcomes were markedly positive:\n- 15% body weight loss achieved\n- Sustained triglyceride reduction maintained\n- No recurrence of acute pancreatitis while on GLP-1RA therapy\n\nThis challenges the blanket avoidance of GLP-1RAs in patients with pancreatitis history and suggests that when severe hypertriglyceridemia is the root cause, the triglyceride-lowering benefit may outweigh the theoretical pancreatitis risk.","whyItMatters":"Severe hypertriglyceridemia causes about 10% of acute pancreatitis cases and tends to recur. Managing triglycerides in these patients is crucial but often difficult. GLP-1RAs are powerful triglyceride-lowering agents, but their package insert warns about pancreatitis, creating a therapeutic dilemma. This case suggests that for HTG-induced pancreatitis specifically, GLP-1RAs may actually prevent recurrence by addressing the root cause — a paradigm shift in how we think about the pancreatitis warning.","specificNumbers":"","methodology":"Single patient case report documenting the clinical course of a 42-year-old woman with recurrent hypertriglyceridemia-induced acute pancreatitis who was initiated on GLP-1RA therapy. Weight, triglyceride levels, and pancreatitis recurrence were monitored during treatment.","limitations":"This is a single case report — the lowest level of clinical evidence. The positive outcome in one patient cannot be generalized to all patients with HTG-induced pancreatitis. Confounding factors (other medications, dietary changes, time) cannot be controlled for. The duration of follow-up is not specified in the abstract. A single case cannot definitively establish that GLP-1RAs are safe in pancreatitis patients; randomized trials would be needed."},{"rthcId":"RPEP-11232","title":"Calprotectin Level and Its Relationship with Right Ventricular Function in Patients with Pulmonary Embolism.","authors":"Gurbuz, Ahmet Seyfeddin; Sahin, Ahmet Taha; Sarı, Hasan; Kesriklioglu, Serhat","year":2025,"journal":"Acta Cardiologica Sinica, 41(4), 530-538","doi":"10.6515/ACS.202507_41(4).20250224F","pmid":"40740209","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11233","title":"Multifaceted Marine Peptides and Their Therapeutic Potential.","authors":"Guryanova, Svetlana V; Ovchinnikova, Tatiana V","year":2025,"journal":"Marine drugs, 23(7)","doi":"10.3390/md23070288","pmid":"40710513","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11234","title":"Advanced peptide nanoparticles enable robust and efficient delivery of gene editors across cell types.","authors":"Gustafsson, Oskar; Krishna, Supriya; Borate, Sophia; Ghaeidamini, Marziyeh; Liang, Xiuming; Saher, Osama; Cuellar, Raul; Birdsong, Björn K; Roudi, Samantha; Estupiñán, H Yesid; Alici, Evren; Smith, C I Edvard; Esbjörner, Elin K; Spuler, Simone; de Jong, Olivier Gerrit; Escobar, Helena; Nordin, Joel Z; Andaloussi, Samir E L","year":2025,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 386, 114038","doi":"10.1016/j.jconrel.2025.114038","pmid":"40684990","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11235","title":"Compounded Tirzepatide Therapy for Weight Loss: A Health Economics & Outcomes Research (HEOR) Analysis.","authors":"Guth, Michael As","year":2025,"journal":"International journal of pharmaceutical compounding, 29(1), 52-63","doi":null,"pmid":"39921911","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11236","title":"Vasoactive Intestinal Peptide (VIP) in COVID-19 Therapy-Shedding of ACE2 and TMPRSS2 via ADAM10.","authors":"Gutzler, Charlotte; Höhne, Kerstin; Bani, Daniele; Kayser, Gian; Fähndrich, Sebastian; Ambros, Michael; Hug, Martin J; Rieg, Siegbert; Falcone, Valeria; Müller-Quernheim, Joachim; Zissel, Gernot; Frye, Björn C","year":2025,"journal":"International journal of molecular sciences, 26(6)","doi":"10.3390/ijms26062666","pmid":"40141308","tags":["vip","antiviral-peptides"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Vasoactive intestinal peptide (VIP) reduced SARS-CoV-2 infection of epithelial cells through a dual mechanism. First, VIP downregulated both ACE2 and TMPRSS2 — the two proteins the virus uses to enter cells — at both the mRNA and surface protein levels. Second, VIP upregulated a protease called ADAM10, which physically strips ACE2 and TMPRSS2 from the cell surface (a process called shedding).\n\nThe combined effect of these two mechanisms — reduced production plus active removal — resulted in fewer viral entry points on cell surfaces and a measurably reduced infection rate when cells were challenged with a SARS-CoV-2 pseudovirus. The researchers suggest the ADAM10 connection may have implications beyond COVID-19.","whyItMatters":"VIP has already been tested in COVID-19 clinical trials based on its known anti-inflammatory properties, but this study reveals an entirely new mechanism: VIP doesn't just dampen the inflammatory response to infection, it may actually reduce viral entry itself by stripping the virus's doorway proteins off cell surfaces. The ADAM10 shedding mechanism is particularly interesting because it could apply to other viruses that use ACE2 or TMPRSS2 for cell entry.","specificNumbers":"ACE2 and TMPRSS2 mRNA downregulated · Surface expression of both proteins reduced · ADAM10 upregulated · SARS-CoV-2 pseudovirus infection rate reduced","methodology":"Researchers used CaCo-2 epithelial cells (a human intestinal cell line) stimulated with SARS-CoV-2 spike protein and treated with native VIP. They measured mRNA expression of ACE2 and TMPRSS2, surface protein expression of both, TMPRSS2 enzyme activity, ADAM10 expression, and infection rates using a SARS-CoV-2 pseudovirus system.","limitations":"This is an in-vitro study using a single cell line (CaCo-2 intestinal cells), which may not reflect the complexity of SARS-CoV-2 infection in lungs or other organs. A pseudovirus was used rather than live SARS-CoV-2. No animal or human data was generated. The study doesn't establish optimal VIP doses for antiviral effects or whether these effects can be achieved in living organisms."},{"rthcId":"RPEP-11237","title":"Cortexin modulates OPG/RANK/RANKL and TRPC1 expression in cerebral ischemia-reperfusion injury.","authors":"Guven, Cengiz; Türk, Ahmet; Koçak, Seda; Zencirci, Busra; Yalcin, Alper; Aydın, Hasan; Doğukan, Mevlut","year":2025,"journal":"Neurological research, 1-12","doi":"10.1080/01616412.2025.2536075","pmid":"40783844","tags":["neuroprotection","cortexin","stroke","oxidative-stress"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"In rats subjected to cerebral ischemia-reperfusion injury, Cortexin treatment significantly reduced total oxidant status (TOS) and increased total antioxidant status (TAS) compared to untreated injury groups. The ischemia and I/R groups showed significantly elevated TOS (p = 0.012 and p = 0.005) and decreased TAS (p = 0.000) versus controls.\n\nCortexin also modulated the expression of key biomarkers in brain tissue: OPG (a protective factor against cell death), RANK/RANKL (inflammatory signaling), and TRPC1 (calcium channel involved in neuronal function). The effects were observed at both 1 mg/kg and 2 mg/kg doses. However, some inflammatory markers remained elevated despite treatment, suggesting Cortexin partially but not completely reversed the inflammatory response.","whyItMatters":"Stroke is a leading cause of death and disability worldwide, and the damage that occurs when blood flow is restored (reperfusion injury) has no targeted treatment. Cortexin has been used clinically in Russia and some Eastern European countries for decades for neurological conditions, but its mechanisms have been poorly understood. This study provides molecular evidence for how it might protect the brain — through antioxidant effects and modulation of inflammatory and calcium signaling pathways — which could support its investigation in more rigorous clinical trials.","specificNumbers":"n=35 rats; 5 groups of 7; 45-min ischemia + 7-day reperfusion; TOS p=0.012/0.005; TAS p=0.000; 1 and 2 mg/kg Cortexin doses","methodology":"35 male Wistar rats divided into 5 groups: control, ischemia only (45 minutes), ischemia-reperfusion (7 days), and two Cortexin treatment groups (1 mg/kg and 2 mg/kg during reperfusion). On day 8, brain tissue was analyzed by immunohistochemistry for OPG, RANK, RANKL, and TRPC1 expression. Serum total oxidant status (TOS) and total antioxidant status (TAS) were measured by ELISA.","limitations":"This was a small animal study (35 rats, 7 per group), which limits statistical power. The abstract contains apparent formatting errors in the p-values, making some results difficult to interpret. Cortexin is a complex mixture of peptides, not a single defined molecule, which complicates mechanistic interpretation. The 7-day treatment period is short. No behavioral or functional outcomes were measured — only biomarker expression. The study was not blinded according to the abstract. Results from rat stroke models frequently fail to translate to human stroke treatment."},{"rthcId":"RPEP-11238","title":"Chronification of migraine sensitizes to CGRP in male and female mice.","authors":"Guzman, Gege; Kopruszinski, Caroline M; Barber, Kara R; Lillo Vizin, Robson C; Dodick, David W; Navratilova, Edita; Porreca, Frank","year":2025,"journal":"Cephalalgia : an international journal of headache, 45(2), 3331024251317446","doi":"10.1177/03331024251317446","pmid":"39945018","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11239","title":"Alpha-CGRP as a specific response mediator during acute myocardial infarction in humans: findings from an observational longitudinal study.","authors":"Gárate, G; Gangas, L; de la Torre, J M; Muñoz San-Martín, M; Pascual, J; González-Quintanilla, V","year":2025,"journal":"Frontiers in cardiovascular medicine, 12, 1581056","doi":"10.3389/fcvm.2025.1581056","pmid":"40589453","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11240","title":"Sequence, characterization and pharmacological analyses of the adipokinetic hormone receptor in the stick insect, Carausius morosus.","authors":"Gäde, Gerd; Tan, Jinghan; Afifi, Salwa; Paluzzi, Jean-Paul V; Jackson, Graham E; Marco, Heather G","year":2025,"journal":"Frontiers in endocrinology, 16, 1601334","doi":"10.3389/fendo.2025.1601334","pmid":"40747312","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11241","title":"Insulin DEgludec/LIraglutide versus multiple daily insulin injections in the transition from hospital to outpatient management assessed by continuous glucose monitoring: the DELI transition trial.","authors":"Gómez-Medina, Ana M; Henao-Carillo, Diana C; Villamil-Castañeda, Lina P; Gómez-Quesada, Yaline; Muñoz-Velandia, Oscar M; Yepes, Carlos A; Chaim, Salma N; Pertuz-Noriega, Carlos E; Aschner, Pablo","year":2025,"journal":"Diabetologia, 68(9), 1899-1907","doi":"10.1007/s00125-025-06446-y","pmid":"40760249","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11242","title":"Evaluating Treatment Success in CGRP Antibody Prophylaxis: A Retrospective Cohort Study Comparing Monthly Migraine Days, MIDAS Scores, and HIT-6 Scores.","authors":"Göbel, Carl H; Heinze, Axel; Heinze-Kuhn, Katja; Müller, Ursula; Cirkel, Anna; Göbel, Hartmut","year":2025,"journal":"Pain and therapy, 14(6), 1899-1914","doi":"10.1007/s40122-025-00784-w","pmid":"41123845","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11243","title":"Brain-derived uroguanylin as a regulator of postprandial brown adipose tissue activation: a potential therapeutic approach for metabolic disorders.","authors":"Habek, Nikola; Ratko, Martina; Sedmak, Dora; Banovac, Ivan; Crljen, Vladiana; Kordić, Milan; Radmilović, Marina; Škokić, Siniša; Tkalčić, Martina; Mažuranić, Anton; Bubalo, Pero; Škavić, Petar; Ljubić, Spomenka; Rahelić, Dario; Dugandžić, Aleksandra","year":2025,"journal":"Frontiers in pharmacology, 16, 1569163","doi":"10.3389/fphar.2025.1569163","pmid":"40351439","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11244","title":"Therapeutic Effects of Phytoestrogen Naringenin in Polycystic Ovary Syndrome (PCOS): Involvement of Kisspeptin and Calcitonin Gene Related Peptide Signalling Pathways.","authors":"Habibi, Manizheh; Mahmoudi, Fariba; Haghighat, Khadijeh; Khazali, Homayoun","year":2025,"journal":"Reports of biochemistry & molecular biology, 14(1), 38-45","doi":"10.61882/rbmb.14.1.38","pmid":"41531654","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In the PCOS rat model, hypothalamic expression of both Kiss1 (kisspeptin) and Cgrp (calcitonin gene-related peptide) genes was significantly elevated compared to healthy controls (p≤0.05). Treatment with naringenin at both dose levels (20 mg/kg and 50 mg/kg) significantly reduced Kiss1 and Cgrp gene expression compared to the untreated PCOS group (p≤0.05).\n\nThis represents a novel mechanistic finding — while naringenin's effects on PCOS have been previously reported, this is the first demonstration that its benefits may involve modulation of hypothalamic kisspeptin and CGRP signaling pathways.","whyItMatters":"PCOS affects up to 10% of women of reproductive age and is a leading cause of infertility. Current treatments are limited and often focus on symptoms rather than underlying causes. Kisspeptin is a master regulator of reproductive hormones, and its dysregulation is thought to drive the hormonal imbalances in PCOS. If naringenin can correct kisspeptin signaling, it could represent a natural approach to addressing the root cause of PCOS rather than just managing symptoms.","specificNumbers":"","methodology":"Twenty female rats (180-200 g) were divided into four groups: control, PCOS (untreated), PCOS + naringenin 20 mg/kg, and PCOS + naringenin 50 mg/kg. PCOS was induced by intramuscular injection of 2 mg estradiol valerate per rat. Control and PCOS groups received saline, while treatment groups received naringenin intraperitoneally. After treatment, hypothalamic tissue was collected and Kiss1 and Cgrp gene expression was measured using real-time PCR.","limitations":"This is a small preclinical study with only 20 rats (5 per group), which limits statistical power. The rat PCOS model induced by estradiol valerate may not fully replicate the complex pathophysiology of human PCOS. Only gene expression was measured — protein levels and functional reproductive outcomes (ovulation, hormone levels, fertility) were not assessed. Naringenin was given intraperitoneally rather than orally, which does not reflect how it would be consumed by humans. No dose-response comparison between the 20 and 50 mg/kg groups is detailed."},{"rthcId":"RPEP-11245","title":"Use of Semaglutide (Wegovy) in Adults in France: A Nationwide Drug Utilization Study.","authors":"Haddy, Nadia; Jourdain, Hugo; Desplas, David; Bertrand, Marion; Jabagi, Marie-Joelle; Rives-Lange, Claire; Zureik, Mahmoud","year":2025,"journal":"BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy, 39(2), 321-332","doi":"10.1007/s40259-024-00699-6","pmid":"39930059","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11246","title":"Advancing Diabetes Management and Glycemic Control While Exploring CagriSema's Impact on Obesity Management.","authors":"Hadid, Somar; Frishman, William H; Aronow, Wilbert S","year":2025,"journal":"Cardiology in review","doi":"10.1097/CRD.0000000000000940","pmid":"40327810","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11247","title":"Enhancing Progestin Therapy with a Glucagon-Like Peptide 1 Agonist for the Conservative Management of Endometrial Cancer.","authors":"Hagemann, Andrea R; Hagemann, Ian S; Mutch, David G; Devor, Eric J; Malmrose, Paige K; Zhang, Yuping; Morrison, Abigail M; Thiel, Kristina W; Leslie, Kimberly K","year":2025,"journal":"Cancers, 17(4)","doi":"10.3390/cancers17040598","pmid":"40002193","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Key findings from cell line and patient-derived organoid (PDO) experiments:\n\n1. Endometrial cancer cell lines (Hec50, KLE, Ishikawa) all express GLP-1 receptors (confirmed by qPCR and Western blot)\n2. GLP-1R agonist treatment induces its own receptor expression through positive feedback\n3. Patient-derived organoids from 6 individuals with grade 1 endometrial carcinomas showed significant viability reduction with levonorgestrel + semaglutide combination — in both progesterone receptor-high AND progesterone receptor-low tumors\n4. Most striking: semaglutide upregulated not only membrane GLP-1R but also nuclear progesterone receptors (PR) and membrane progesterone receptors (PGRMC1/2)\n5. This creates a synergistic feedback loop: semaglutide makes tumors more responsive to levonorgestrel, while levonorgestrel makes them more responsive to semaglutide","whyItMatters":"Endometrial cancer is the most common gynecologic cancer, and its incidence is rising alongside obesity rates. For young women who want to preserve fertility, conservative progestin treatment is an alternative to hysterectomy — but response rates are only about 50-75%, and many patients relapse. Adding semaglutide could both address the underlying obesity risk factor and directly enhance progestin therapy through the newly discovered receptor cross-talk. The finding that even progesterone receptor-low tumors (which typically resist progestin therapy) responded to the combination is particularly exciting.","specificNumbers":"","methodology":"GLP-1R expression was assessed in three endometrial cancer cell lines (Hec50, KLE, Ishikawa) by qPCR and Western blotting. Patient-derived organoids (PDOs) were generated from 6 individuals with grade 1 endometrial carcinomas. PDOs were treated with progesterone, levonorgestrel, semaglutide, or levonorgestrel + semaglutide combination. Viability was measured. Receptor expression changes (GLP-1R, PR, PGRMC1/2) were analyzed to characterize the molecular cross-talk between pathways.","limitations":"This is an in vitro study using cell lines and organoids — results may not translate to human tumors in the complex in vivo environment. Only grade 1 endometrial carcinomas were studied (the least aggressive type). Six organoid models is a small number. The mechanism of receptor cross-talk is described but not fully dissected at the signaling pathway level. Whether the combination would be effective in vivo, at what semaglutide doses, and with what safety profile for fertility preservation are all unknown. The positive feedback loop, while potentially beneficial, could also have unintended consequences."},{"rthcId":"RPEP-11248","title":"Racial Inequity in Prescription of Semaglutide Among Eligible People With HIV.","authors":"Hahn, Andrew W; Ruderman, S A; Nance, R M; Whitney, B M; Eltonsy, S; Haidar, L; Drumright, L N; Ma, J; Mayer, K H; Napravnik, S; Eron, J J; Christopoulos, K A; Bamford, L; Cachay, E R; Yendewa, G; Pettit, A; Saag, M S; Heath, S L; Moore, R D; Keruly, J C; Batey, D S; Chander, G; Kitahata, M M; Delaney, J A C; Crane, H M; Fredericksen, R J","year":2025,"journal":"Diabetes care, 48(10), 1761-1765","doi":"10.2337/dc25-0236","pmid":"40971637","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11249","title":"Fremanezumab for the Treatment of Migraine Complicated by Medication Overuse: A Systematic Review.","authors":"Hajjaj, Ibrahim; Baraldi, Carlo; Pellesi, Lanfranco","year":2025,"journal":"Clinical drug investigation, 45(5), 247-254","doi":"10.1007/s40261-025-01433-y","pmid":"40121372","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Fremanezumab, an anti-CGRP monoclonal antibody, effectively reduced migraine frequency, acute medication use, and headache-related disability in adults with migraine complicated by medication overuse. Clinical trial post hoc analyses showed significant reductions in monthly migraine days, acute headache medication use days, and HIT-6 disability scores compared to placebo over 12 weeks. Real-world studies demonstrated sustained reductions in monthly headache days at 6 months and a high reversion rate from medication overuse headache after one year of treatment.","whyItMatters":"Medication overuse headache is a vicious cycle where the very drugs used to treat migraines end up making them worse. This review shows that fremanezumab — which works by blocking the CGRP peptide pathway rather than simply masking pain — can break this cycle, reducing both migraine frequency and the reliance on overused medications. This is particularly important because these patients are among the hardest to treat.","specificNumbers":"n=1,422 · 2 clinical trials + 7 real-world studies · 176 records screened · 12-week trial periods · 6-month and 1-year real-world follow-up · reduced monthly migraine days, medication use, and HIT-6 scores","methodology":"This systematic review searched PubMed and Embase databases for studies on fremanezumab in adults with migraine complicated by medication overuse. From 176 records, 2 clinical trials and 7 real-world studies were included. Randomized controlled trials were assessed for bias using the Cochrane RoB 2 tool, and real-world studies were evaluated using ROBINS-I and ROB-ME tools.","limitations":"Most efficacy data came from post hoc analyses of clinical trials rather than pre-specified primary endpoints for this population. The overall quality of evidence was limited, and real-world studies lacked standardized reporting criteria. More robust prospective studies are needed to confirm long-term benefits."},{"rthcId":"RPEP-11250","title":"The potential role of calcitonin gene-related peptide antagonists for the management of hangover headaches.","authors":"Hakim, Sameh M","year":2025,"journal":"Current opinion in anaesthesiology, 38(5), 669-673","doi":"10.1097/ACO.0000000000001553","pmid":"40704605","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11251","title":"Growth hormone-releasing hormone receptor (GHRH-R) and its signaling.","authors":"Halmos, Gabor; Szabo, Zsuzsanna; Dobos, Nikoletta; Juhasz, Eva; Schally, Andrew V","year":2025,"journal":"Reviews in endocrine & metabolic disorders, 26(3), 343-352","doi":"10.1007/s11154-025-09952-x","pmid":"39934495","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11252","title":"Dual-sensitive gelatin-coated chitosan microparticles for targeted semaglutide pulmonary delivery: a novel approach to enhancing anti-inflammatory and anti-fibrotic effects.","authors":"Hamad, Rabab S; Kira, Ahmed Y; Saber, Sameh; Alharbi, Mariam S; Alsaykhan, Hamad; Ahmed, Syed Suhail; Ahmed, Hagir H T; Ahmed, Amel; Farrag, Alshaimaa A; Eissa, Hanan; Mohamed, Nahla B; Khodeir, Mostafa M; Hatem, Manal Mohamed; Alghasham, Abdullah; Abdel-Reheim, Mustafa Ahmed; Ramadan, Mohamed; Sameh, Ahmed; Elmorsy, Elsayed A","year":2025,"journal":"International immunopharmacology, 165, 115480","doi":"10.1016/j.intimp.2025.115480","pmid":"40915185","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11253","title":"Insulin Sensitivity and Beta-Cell Function Following Tirzepatide in Japanese Patients with Type 2 Diabetes: A SURPASS J-mono Analysis.","authors":"Hamamoto, Yoshiyuki; Oura, Tomonori; Hirase, Tetsuaki","year":2025,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 16(4), 717-729","doi":"10.1007/s13300-025-01704-z","pmid":"39951042","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11254","title":"Cardiovascular Safety Profile of Semaglutide and Variations by Sex, Race, and Kidney Function: A Systematic Review and Meta-analysis.","authors":"Hamayal, Muhammad; Akhtar, Chaudhary Humayun; Ahmad, Naveed; Awwab, Muhammad; Shahid, Warda; Abbasi, Hasan Shaukat; Nadeem, Esha; Siddiqui, Erum; Zafar, Wadana; Hussain, Saima","year":2025,"journal":"American journal of cardiovascular drugs : drugs, devices, and other interventions, 25(4), 479-489","doi":"10.1007/s40256-025-00727-y","pmid":"40106161","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11255","title":"Bioactive peptides with potential anticancer properties from various food protein sources: status of recent research, production technologies, and developments.","authors":"Hamdi, Marwa; Kilari, Bhanu Priya; Mudgil, Priti; Nirmal, Nilesh Prakash; Ojha, Shreesh; Ayoub, Mohammed Akli; Amin, Amr; Maqsood, Sajid","year":2025,"journal":"Critical reviews in biotechnology, 45(5), 1076-1097","doi":"10.1080/07388551.2024.2435965","pmid":"39757011","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11256","title":"Results of cardiovascular testing among pregnant and postpartum persons undergoing standardized cardiovascular risk assessment.","authors":"Hameed, Afshan B; Tarsa, Maryam; Waks, Ashten; Grodzinsky, Anna; Florio, Karen L; Chang, Jenny; Jacobs, Marni B; Balogun, Omotayo I; Thiel de Bocanegra, Heike","year":2025,"journal":"American journal of obstetrics & gynecology MFM, 7(5), 101656","doi":"10.1016/j.ajogmf.2025.101656","pmid":"39988191","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11257","title":"CGRP-dependent molecular signaling drives bone marrow stem cell osteogenesis in distraction osteogenesis.","authors":"Hamiti, Yimurang; Liu, Kai; Wang, Sulong; Yang, Xin; Kadier, Xiriaili; Yusufu, Aihemaitijiang","year":2025,"journal":"Frontiers in bioengineering and biotechnology, 13, 1641476","doi":"10.3389/fbioe.2025.1641476","pmid":"41069411","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11258","title":"CGRP-releasing PLGA/nHA/GO composite microspheres enhance distraction osteogenesis via activation of the cAMP/PKA/CREB pathway.","authors":"Hamiti, Yimurang; Liu, Kai; Yang, Xin; Wang, Sulong; Kadier, Xiriaili; Yusufu, Aihemaitijiang","year":2025,"journal":"Materials today. Bio, 34, 102181","doi":"10.1016/j.mtbio.2025.102181","pmid":"40893374","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11259","title":"Semaglutide Aggregates into Oligomeric Micelles and Short Fibrils in Aqueous Solution.","authors":"Hamley, Ian W; de Mello, Lucas R; Castelletto, Valeria; Zinn, Thomas; Cowieson, Nathan; Seitsonen, Jani; Bizien, Thomas","year":2025,"journal":"Biomacromolecules, 26(6), 3786-3794","doi":"10.1021/acs.biomac.5c00342","pmid":"40355389","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11260","title":"Exploring the multifaceted roles of GLP-1 receptor agonists; a comprehensive review.","authors":"Hammad, Bisma Fatima; Zafar, Nimrah; Ullah, Muneeb; Faisal, Syeda Jazilah; Iftikhar, Fizzah; Waheed, Haadia; Muzaffar, Muhammad Waleed; Ahmed, Khadija; Ashraf, Faz; Zahid, Komal; Akhtar, Maimoona; Mahmmoud Fadelallah Eljack, Mohammed","year":2025,"journal":"Frontiers in clinical diabetes and healthcare, 6, 1590530","doi":"10.3389/fcdhc.2025.1590530","pmid":"40708853","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 receptors are widely distributed across multiple organ systems — brain, lungs, pancreas, stomach, heart, and endometrium — which explains the broad therapeutic potential of GLP-1 receptor agonists beyond their original diabetes indication.\n\nRecent studies demonstrate physiological effects across these organ systems: blood glucose regulation and pancreatic beta-cell function, weight management through appetite suppression and metabolic effects, cardiovascular protection including reduced major adverse cardiovascular events, potential neuroprotective effects relevant to neurodegenerative diseases, and positive influences on musculoskeletal health. While clinical efficacy for diabetes and obesity is well established, many of these expanded indications are still being investigated.","whyItMatters":"GLP-1 receptor agonists have become one of the most prescribed drug classes globally, and understanding their full therapeutic potential is crucial for maximizing patient benefit. This review provides a broad overview of where these drugs might help beyond diabetes — from protecting the heart and brain to supporting bone health — helping clinicians and patients understand the possible additional benefits of treatments they may already be taking.","specificNumbers":"","methodology":"This is a comprehensive narrative review synthesizing recent published studies on the expanding therapeutic applications of GLP-1 receptor agonists. The review examines the physiological rationale (GLP-1 receptor distribution), clinical evidence across multiple organ systems, and identifies gaps in the current evidence base including long-term safety and cost-effectiveness data.","limitations":"As a narrative review, the article is subject to selection bias in which studies are highlighted. Many of the expanded therapeutic applications discussed (neuroprotection, musculoskeletal health) are based on preclinical data or early-stage clinical evidence, not definitive large-scale trials. The review acknowledges significant gaps in long-term safety data and cost-effectiveness research. It does not provide a systematic or quantitative analysis of the evidence."},{"rthcId":"RPEP-11261","title":"Beyond Glycemic Control: Concurrent GLP-1 Receptor Agonist Use Is Associated with Reduced Urinary Adverse Events Following OnabotulinumtoxinA Treatment in Non-Diabetic Adults with Overactive Bladder.","authors":"Hammad, Muhammed A M; Quesada, Sophia G; Belczyk, Aimee L; Ghoniem, Gamal M","year":2025,"journal":"Toxins, 17(11)","doi":"10.3390/toxins17110542","pmid":"41295856","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11262","title":"Tirzepatide for overweight and obesity management.","authors":"Hamza, Malak; Papamargaritis, Dimitris; Davies, Melanie J","year":2025,"journal":"Expert opinion on pharmacotherapy, 26(1), 31-49","doi":"10.1080/14656566.2024.2436595","pmid":"39632534","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11263","title":"Mucoadhesive Mini-Containers with Unidirectional Drug Release Capacity for Macromolecular Therapeutics.","authors":"Han, Chang-Soo; Choi, Ye-Rin; Jung, Woong-Young; Kang, Ji-Hyun; Kim, Dong-Wook; Park, Chun-Woong","year":2025,"journal":"Drug design, development and therapy, 19, 6619-6635","doi":"10.2147/DDDT.S521900","pmid":"40766820","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11264","title":"Design, synthesis, and antitumor activity of stapled peptide inhibitors targeting the RAS-RAF interactions.","authors":"Han, Dan; Yu, Zhou; Zhang, Kai; Gai, Conghao; Zhang, Peichao; Chai, Xiaoyun; Zhuo, Xiaobing; Zhao, Qingjie; Zou, Yan; Zhu, Lie","year":2025,"journal":"European journal of medicinal chemistry, 290, 117568","doi":"10.1016/j.ejmech.2025.117568","pmid":"40153928","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11265","title":"Immunomodulatory peptide-drug conjugate MEL-dKLA suppresses progression of prostate cancer by eliminating M2-like tumor-associated macrophages.","authors":"Han, Ik-Hwan; Choi, Ilseob; Kim, Soyoung; Kwon, Minjin; Choi, Hyojung; Bae, Hyunsu","year":2025,"journal":"Frontiers in immunology, 16, 1652166","doi":"10.3389/fimmu.2025.1652166","pmid":"41019043","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The peptide-drug conjugate MEL-dKLA — combining melittin (which selectively binds M2-like macrophages) with the pro-apoptotic peptide dKLA — preferentially bound to and killed tumor-associated macrophages (TAMs) that promote cancer growth. In cell culture, treating M2 macrophages with MEL-dKLA reduced their ability to stimulate prostate cancer cell proliferation, migration, and invasion.\n\nIn a mouse prostate cancer model, MEL-dKLA treatment significantly reduced tumor growth, decreased CD163+ M2 macrophages in tumors, and increased CD8+ killer T cell infiltration — effectively reprogramming the tumor microenvironment from immunosuppressive to immune-active.","whyItMatters":"Prostate cancer often creates an immunosuppressive microenvironment using tumor-associated macrophages that shield it from immune attack. Rather than targeting cancer cells directly, this peptide conjugate eliminates the immune-suppressing macrophages, allowing the body's own T cells to attack the tumor. This approach represents a fundamentally different strategy in cancer immunotherapy — using peptides to reshape the tumor environment rather than directly kill cancer cells.","specificNumbers":"2 peptide components (melittin + dKLA) · Selective M2 macrophage binding confirmed · Tumor growth significantly reduced in vivo · CD163+ macrophages decreased · CD8+ T cells increased in tumors","methodology":"Researchers differentiated human THP-1 monocytes into TAMs using tumor-conditioned medium. MEL-dKLA binding specificity was tested with fluorescent-labeled melittin. Functional effects were measured through proliferation, migration, and invasion assays using PC-3 prostate cancer cells. In vivo efficacy was tested in mice bearing TRAMP-C2 prostate tumors, with MEL-dKLA administered every three days. Tumor immune cell composition was analyzed by immunostaining.","limitations":"The mouse model uses subcutaneous tumor implantation, which does not fully replicate human prostate cancer biology or the tumor microenvironment. The study did not test long-term effects, potential toxicity to normal macrophages, or resistance mechanisms. Melittin is derived from bee venom and may have off-target effects at higher doses. Translation to human prostate cancer would require extensive safety and efficacy testing."},{"rthcId":"RPEP-11266","title":"Cyclic Hydroxylamines for Native Residue-Forming Peptide Ligations: Synthesis of Ubiquitin and Tirzepatide.","authors":"Han, Jiling; Hirao, Kohtaro; Mikami, Toshiki; Nötel, Nicolas Y; Seidl, Leonardo L; Bode, Jeffrey W","year":2025,"journal":"Journal of the American Chemical Society, 147(38), 34238-34243","doi":"10.1021/jacs.5c11881","pmid":"40934092","tags":[],"studyType":"methodology","evidenceStrength":"preliminary","keyFinding":"Researchers developed new chemical building blocks (cyclic dipeptide-derived hydroxylamines) that enable peptide ligation at fully native sites — meaning no unnatural amino acids are left behind at the joining point. They demonstrated the method by synthesizing two challenging targets: ubiquitin (for protein research) and tirzepatide (the GLP-1/GIP dual agonist drug).\n\nThe tirzepatide synthesis was particularly notable because the drug contains non-standard features — amino-isobutyric acid (Aib) residues and a fatty acid side chain — that make it extremely difficult to produce by traditional methods. The new approach successfully joined unprotected peptide segments at 'nonobvious' junctions like Leu-Ile and Lys-Ile.","whyItMatters":"Tirzepatide (Mounjaro/Zepbound) is one of the most important peptide drugs ever developed, but its complex structure makes manufacturing challenging and expensive. This new ligation chemistry could enable more efficient synthesis of tirzepatide and similarly complex peptide therapeutics. By allowing native amino acid formation at ligation sites, it removes a key limitation that has restricted chemical synthesis approaches for large therapeutic peptides.","specificNumbers":"Tirzepatide total synthesis achieved · ubiquitin synthesis demonstrated · Leu-Ile and Lys-Ile junctions enabled · native residue formation at ligation sites · Aib-containing peptide synthesized · fatty acid side chain incorporated","methodology":"Organic chemistry method development. Researchers designed cyclic dipeptide-derived hydroxylamine building blocks for KAHA (α-ketoacid-hydroxylamine) ligation. They optimized reaction conditions for native residue formation, then demonstrated the approach by synthesizing selectively protected ubiquitin monomers and performing the total chemical synthesis of tirzepatide.","limitations":"Pure chemistry methodology — no biological testing of the synthesized tirzepatide. Scalability to manufacturing quantities was not demonstrated. The building blocks require multi-step preparation from dipeptides. Cost comparison with existing tirzepatide manufacturing (recombinant production) was not addressed. Limited to specific ligation junctions."},{"rthcId":"RPEP-11267","title":"DOPC Liposomal Formulation of Antimicrobial Peptide LL17-32 with Reduced Cytotoxicity: A Promising Carrier Against Porphyromonas gingivalis.","authors":"Han, Jinyang; Meade, Josephine L; Goycoolea, Francisco M","year":2025,"journal":"Pharmaceutics, 17(11)","doi":"10.3390/pharmaceutics17111424","pmid":"41304762","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11268","title":"In Situ Probing the Effects of Lipid Packing Density and Concentration of CPPs on the Transmembrane Process at the Air-Water Interface.","authors":"Han, Linyu; Liu, Caihe; Zhang, Yuening; Qin, Xujin; Guo, Yuan; Liu, Minghua; Zhang, Zhen","year":2025,"journal":"The journal of physical chemistry letters, 16(51), 13027-13037","doi":"10.1021/acs.jpclett.5c02798","pmid":"41383133","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The cell-penetrating peptide penetratin (PEN) exhibits a nonmonotonic concentration threshold effect when interacting with sphingomyelin membranes. At optimal concentrations, PEN promotes structural ordering that facilitates membrane crossing, but beyond this threshold, it causes excessive disruption that reduces efficiency.\n\nThe study revealed asymmetric chain reorganization in lipid molecules, with sphingosine terminal methyl orientation shifting from 32° to 55° depending on conditions, while N-alkyl chain angles remained stable (32°–38°). At high lipid packing density (30 mN/m), elevated hydrogen-bond networks correlate with non-bonded peptide carbonyl states, while low density (10 mN/m) promotes hydrogen-bonded peptide adsorption to the membrane surface.","whyItMatters":"Cell-penetrating peptides are one of the most promising tools for delivering drugs — including peptide therapeutics — into cells. Understanding exactly why their efficiency changes with concentration could help researchers design better drug delivery systems with more predictable dosing behavior, potentially improving how peptide-based medications reach their targets inside cells.","specificNumbers":"","methodology":"Researchers used in situ high-resolution broadband sum-frequency generation vibrational spectroscopy (SFG-VS) to study molecular interactions between the penetrating peptide PEN and egg sphingomyelin monolayers at an air-water interface. This technique allowed them to observe molecular-level changes in real time as peptide concentration and lipid packing density were varied.","limitations":"This was an in vitro study using simplified lipid monolayers at an air-water interface, which doesn't fully replicate the complexity of real cell membranes (bilayers with proteins, cholesterol, and other components). Only one CPP (penetratin) and one lipid (egg sphingomyelin) were tested, so the findings may not generalize to all CPP-lipid combinations. No cellular or in vivo experiments were performed."},{"rthcId":"RPEP-11269","title":"Gut-brain communication: nerve circuits and chemical messengers of colorectal motility and defecation control.","authors":"Han, Myat Noe; Furness, John B; Ringuet, Mitchell T; Montenegro, Ella; Wu, Hongkang; Hossain, Mohammed Akhter; Diwakarla, Shanti; Dehkhoda, Farhad; Furness, Sebastian G B","year":2025,"journal":"American journal of physiology. Regulatory, integrative and comparative physiology, 329(6), R931-R945","doi":"10.1152/ajpregu.00212.2025","pmid":"41196192","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review integrates foundational and recent research to describe four hierarchical levels of neural control over colorectal motility and defecation:\n\n1. Cortical and hypothalamic centers in the brain\n2. Pontomedullary cell groups in the brainstem\n3. Lumbosacral defecation centers in the spinal cord\n4. The enteric nervous system (ENS) within the gut wall\n\nThe critical link between the central nervous system (CNS) and ENS is provided by parasympathetic preganglionic (PPG) neurons, which express a wide range of amine and peptide receptors. These receptors — including those for ghrelin, dopamine, and serotonin — are identified as potential therapeutic targets for constipation. The importance of CNS-ENS coordination is demonstrated by the severe constipation that follows spinal cord injury or occurs in Parkinson's disease, and by the failed defecation seen in Hirschsprung and Chagas diseases when the ENS is absent.","whyItMatters":"Constipation affects hundreds of millions of people worldwide and is a debilitating symptom of spinal cord injury, Parkinson's disease, and other neurological conditions. Current treatments are often inadequate. By mapping the neural circuits in detail and identifying peptide receptors on key connector neurons, this review provides a roadmap for developing more targeted and effective therapies for bowel dysfunction.","specificNumbers":"","methodology":"This is a comprehensive narrative review that integrates foundational neuroscience knowledge with recent advances in gut-brain signaling research. The authors synthesized evidence from clinical observations (spinal cord injury, Parkinson's disease, Hirschsprung disease, Chagas disease) and preclinical studies to map the neural circuits controlling colorectal motility.","limitations":"As a narrative review, this paper synthesizes existing evidence without presenting new experimental data. The therapeutic targets identified are based on receptor expression patterns and have not been clinically validated for constipation treatment. The complexity of the four-level neural control system means that targeting a single receptor may have limited efficacy. Much of the understanding comes from animal models and disease observations rather than controlled human studies."},{"rthcId":"RPEP-11270","title":"Crucian Carp-Derived ACE-Inhibitory Peptides with In Vivo Antihypertensive Activity: Insights into Bioactivity, Mechanism, and Safety.","authors":"Han, Runxi; Tian, Jingshan; Han, Yingge; Wang, Guoxiang; Zhou, Guanghong; Dai, Chen; Wang, Chong","year":2025,"journal":"Molecules (Basel, Switzerland), 30(13)","doi":"10.3390/molecules30132812","pmid":"40649326","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11271","title":"Association of glucagon-like peptide-1 receptor agonist use with risk of infections: A systematic review and meta-analysis.","authors":"Han, Shumeng; Liu, Yiwen; Xing, Baodi; Yang, Yucheng; Liu, Zijun; Li, Yixuan; Wang, Xuechen; Yu, Jie; Ping, Fan; Li, Wei; Xu, Lingling; Qi, Tao; Zhang, Yuelun; Li, Yuxiu; Zhang, Huabing","year":2025,"journal":"The Journal of infection, 91(5), 106645","doi":"10.1016/j.jinf.2025.106645","pmid":"41173399","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11272","title":"Nose-to-Brain Delivery of Acyl-Ghrelin Peptide Gold Nanoconjugates for Treatment of Neurodegenerative Diseases.","authors":"Han, Shunping; Utami, Rifka N; Qin, Yue; Liam-Or, Revadee; Sreedharan, Jemeen; Davies, Jeffrey S; Al-Jamal, Khuloud T","year":2025,"journal":"Small (Weinheim an der Bergstrasse, Germany), 21(36), e04517","doi":"10.1002/smll.202504517","pmid":"40685769","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11273","title":"Synergistic effects of oral milk ceramide-collagen peptides mixtures in preventing UV-induced inflammation and photoaging through TGF-β and NF-κB/MAPK signaling pathways in UV-exposed hairless mice.","authors":"Han, Sung Hee; Suh, Hyung Joo; Lee, Sang Jun; Chang, Yeok Boo","year":2025,"journal":"Journal of photochemistry and photobiology. B, Biology, 268, 113171","doi":"10.1016/j.jphotobiol.2025.113171","pmid":"40319715","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11274","title":"Liraglutide promotes diabetic corneal epithelial and nerve regeneration by suppressing oxidative stress via the PI3K/AKT signalling pathway.","authors":"Han, Wentao; Dai, Shirui; Sun, Xinyue; Liu, Shaohua; Zhang, Liwei; Chen, Baihua","year":2025,"journal":"European journal of pharmacology, 1007, 178264","doi":"10.1016/j.ejphar.2025.178264","pmid":"41109401","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11275","title":"Genome-wide analysis identifies susceptibility loci for heart failure and nonischemic cardiomyopathy subtype in the East Asian populations.","authors":"Han, Yi; Hong, Yun; Gao, Yan; Lu, Jiapeng; Chen, Bowang; Zhang, Lihua; Yan, Xiaofang; Sun, Ying; Zhang, Liping; Liu, Jiangling; Dai, Hao; Hou, Libo; Li, Xi; Li, Jing","year":2025,"journal":"PLoS genetics, 21(10), e1011897","doi":"10.1371/journal.pgen.1011897","pmid":"41144497","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11276","title":"Prognostic value of echocardiogram and cardiac biomarkers through three waves of COVID-19.","authors":"Han, Yuchen; Long, Grace A; Ali, T 'shura; Deitz, Kailyn; Samanapally, Harideep; Salunkhe, Vidyulata; Deepti, Fnu; Huang, Emma C; Sunkara, Jahnavi; Cermack, Katherine; Huang, Justin J; Wang, Emilia; Davies, J Tyson; Kong, Maiying; Huang, Jiapeng","year":2025,"journal":"Journal of anesthesia and translational medicine, 4(2), 73-79","doi":"10.1016/j.jatmed.2025.05.002","pmid":"41647733","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11277","title":"Inhibition of the angiotensin-converting enzyme N-terminal catalytic domain prevents endogenous opioid degradation in brain tissue.","authors":"Hanak, Filip; Swanson, Jessica L; Felczak, Krzysztof; Bernstein, Kenneth E; More, Swati S; Rothwell, Patrick E","year":2025,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2025.01.21.634163","pmid":"39896517","tags":["enkephalin","ace-inhibitor"],"studyType":"preclinical-mechanistic","evidenceStrength":"moderate-preclinical","keyFinding":"Using brain slices from mutant mice with functional inactivation of either ACE catalytic domain, researchers demonstrated that only N-terminal domain inactivation reduced the degradation of Met-enkephalin-Arg-Phe (MERF) to Met-enkephalin. C-terminal domain inactivation had no effect. A selective N-terminal domain inhibitor (RXP 407) reduced degradation of both exogenously applied and endogenously released MERF, while leaving degradation of Met-enkephalin and Leu-enkephalin unaffected.","whyItMatters":"Current opioid medications work by flooding receptors with synthetic agonists, causing tolerance and addiction. Boosting the brain's own opioid peptides by preventing their breakdown could be safer. This study identifies a precise molecular target — the ACE N-terminal domain — that could enable this strategy.","specificNumbers":"2 ACE catalytic domains studied; N-terminal domain identified as primary MERF degradation site; RXP 407 selective inhibitor tested; both sexes of mice used","methodology":"Researchers used acute brain slice preparations from mice of both sexes, including mutant lines with functional inactivation of either the N-terminal or C-terminal ACE domain. Brain slices were incubated with exogenous MERF at saturating concentration and degradation was measured. A selective N-terminal domain inhibitor (RXP 407) was also tested on degradation of both exogenously applied and endogenously released enkephalin peptides.","limitations":"Preprint not yet peer-reviewed. Ex vivo brain slice study, not in vivo. No behavioral outcomes measured. Translation to human brain physiology unknown. Selective inhibitor tested only in tissue, not in living animals."},{"rthcId":"RPEP-11278","title":"Efficacy and Safety of Glucagon-like Peptide-1 Receptor Agonist Use During the First Trimester in Pregnant Women With Type 2 Diabetes.","authors":"Hanif, Muhammad; Hays, Allison G; Nagarajan, Jai S; Sah, Shiva P; Weinstock, Ruth S; Taub, Cynthia C","year":2025,"journal":"The American journal of cardiology, 246, 10-13","doi":"10.1016/j.amjcard.2025.03.013","pmid":"40107335","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"After propensity score matching of 3,652 first-trimester pregnant women with T2D (average age 36.2 years in the GLP-1RA group), maternal all-cause mortality was comparable between GLP-1RA-exposed and control cohorts at 42 weeks. Secondary maternal outcomes — gestational hypertension, preeclampsia, and eclampsia — were also comparable. Fetal cardiac and kidney anomaly risks were not increased in the GLP-1RA-exposed group. The analysis used a global EHR database of over 140 million patients.","whyItMatters":"GLP-1 receptor agonists are the fastest-growing drug class in medicine, increasingly used by women of reproductive age for both diabetes and weight management. The FDA recommends discontinuation at least 2 months before pregnancy due to animal data suggesting harm, but unplanned pregnancies inevitably expose some women during the first trimester. This is one of the largest studies to date examining what actually happens when this occurs, providing real-world safety data that has been urgently needed.","specificNumbers":"","methodology":"Retrospective propensity score-matched cohort study using a global electronic health records database (>140 million patients). 3,652 women with T2D were identified and divided into GLP-1RA-exposed (within 1 year before and 1 month after first-trimester pregnancy diagnosis) and unexposed cohorts. Propensity score matching controlled for confounders. Primary outcome was maternal all-cause mortality; secondary outcomes included pregnancy complications and fetal anomalies, with 42-week follow-up.","limitations":"This is a retrospective observational study, not a randomized trial. EHR data may have coding errors, missing information, and surveillance bias. The study only examined outcomes through 42 weeks, not long-term child developmental outcomes. Rare adverse events may not be detectable even with 3,652 patients. The abstract appears truncated, suggesting possible reporting limitations. Exposure was defined broadly (within 1 year before and 1 month after pregnancy), so actual drug levels during organogenesis may vary significantly."},{"rthcId":"RPEP-11279","title":"Central nervous system pathways targeted by amylin in the regulation of food intake.","authors":"Hankir, Mohammed K; Le Foll, Christelle","year":2025,"journal":"Biochimie, 229, 95-104","doi":"10.1016/j.biochi.2024.10.012","pmid":"39426704","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11280","title":"Novel neural pathways targeted by GLP-1R agonists and bariatric surgery.","authors":"Hankir, Mohammed K; Lutz, Thomas A","year":2025,"journal":"Pflugers Archiv : European journal of physiology, 477(2), 171-185","doi":"10.1007/s00424-024-03047-3","pmid":"39644359","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11281","title":"Real-world use and effectiveness of tirzepatide among people without evidence of type 2 diabetes in the United States.","authors":"Hankosky, Emily R; Desai, Karishma; Chinthammit, Chanadda; Grabner, Michael; Stockbower, Grace; He, Xuanyao; Mojdami, Donna; Wenziger, Cachet; Gibble, Theresa Hunter","year":2025,"journal":"Diabetes & metabolism, 51(3), 101636","doi":"10.1016/j.diabet.2025.101636","pmid":"40057019","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11282","title":"Real-world use and effectiveness of tirzepatide among individuals without type 2 diabetes: Results from the Optum Market Clarity database.","authors":"Hankosky, Emily R; Chinthammit, Chanadda; Meeks, Alexandra; Huang, Ahong; Ward, Jennifer M; Mojdami, Donna; Gibble, Theresa Hunter","year":2025,"journal":"Diabetes, obesity & metabolism, 27(5), 2810-2821","doi":"10.1111/dom.16290","pmid":"39996368","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11283","title":"Tirzepatide 10 and 15 mg versus semaglutide 2.4 mg in people with obesity or overweight with type 2 diabetes: An indirect treatment comparison.","authors":"Hankosky, Emily R; He, Xuanyao; Malik, Raleigh; Fraseur Brumm, Julia; Wang, Fangyu; Niemeyer, Anthony; Zhang, Xiaotian M; Garvey, W Timothy","year":2025,"journal":"Diabetes, obesity & metabolism, 27(7), 3757-3765","doi":"10.1111/dom.16401","pmid":"40321113","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11284","title":"Tirzepatide and the 10-year predicted risk of cardiovascular disease and type 2 diabetes in adults with obesity and prediabetes: A post hoc analysis from the three-year SURMOUNT-1 trial.","authors":"Hankosky, Emily R; Lebrec, Jeremie; Lee, Clare J; Dimitriadis, Georgios K; Jouravskaya, Irina; Stefanski, Adam; Garvey, W Timothy","year":2025,"journal":"Diabetes, obesity & metabolism, 27(12), 7385-7394","doi":"10.1111/dom.70143","pmid":"41017451","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11285","title":"Age and Sex Differences in Efficacy of Treatments for Type 2 Diabetes: A Network Meta-Analysis.","authors":"Hanlon, Peter; Butterly, Elaine; Wei, Lili; Wightman, Heather; Almazam, Saleh Ali M; Alsallumi, Khalid; Crowther, Jamie; McChrystal, Ryan; Rennison, Heidi; Hughes, Katherine; Lewsey, Jim; Lindsay, Robert; McGurnaghan, Stuart; Petrie, John; Tomlinson, Laurie A; Wild, Sarah; Adler, Amanda; Sattar, Naveed; Phillippo, David M; Dias, Sofia; Welton, Nicky J; McAllister, David A","year":2025,"journal":"JAMA, 333(12), 1062-1073","doi":"10.1001/jama.2024.27402","pmid":"39899304","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 601 trials (309,503 participants for HbA1c; 168,489 for MACE), GLP-1 receptor agonists showed greater cardiovascular risk reduction in younger vs. older people (HR 1.47 per 30-year age increment, 95% CrI 1.07-2.02 — meaning less benefit with age). Conversely, SGLT2 inhibitors showed greater cardiovascular protection in older vs. younger people (HR 0.76 per 30-year increment, 95% CrI 0.62-0.93). For HbA1c, GLP-1 drugs lowered it more in older patients for mono/dual therapy, while SGLT2 inhibitors lowered it less with increasing age. No consistent sex × treatment interactions were found for either drug class.","whyItMatters":"Clinicians currently choose between GLP-1 drugs and SGLT2 inhibitors based mainly on comorbidities and patient preference. This study adds age as a decision factor: younger high-cardiovascular-risk patients may benefit more from GLP-1 drugs, while older patients may benefit more from SGLT2 inhibitors for heart protection. This could fundamentally change prescribing algorithms for the tens of millions of people with type 2 diabetes worldwide.","specificNumbers":"","methodology":"Network meta-analysis and meta-regression using individual participant data (103 trials) and aggregate data from 601 eligible randomized controlled trials. Searched MEDLINE, Embase, and clinical trial registries through August 2024. Multilevel network meta-regression models estimated age × treatment and sex × treatment interactions for HbA1c and MACE outcomes.","limitations":"Individual participant data were available for only 103 of 601 trials. The age-treatment interaction for MACE was based on only 23 trials reporting this outcome. The credible intervals for some interactions are wide. The analysis focused on drug classes, not individual drugs within classes. The mechanisms underlying the age-dependent differences are not explained. Most trial participants were over 55, limiting conclusions about younger adults."},{"rthcId":"RPEP-11286","title":"Repurposing GLP-1 Receptor Agonists: A Perspective on Epigenetic Strategies to Combat Fibrosis and Hepatocellular Carcinoma in the Aged Liver.","authors":"Hanna, Silvia; Sethiadi, Jason; Ali, Qazi; Sinha, Saloni","year":2025,"journal":"Cancers, 17(16)","doi":"10.3390/cancers17162600","pmid":"40867230","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11287","title":"A multidimensional fecal microbial and inflammatory biomarker profiling in preterm and full-term neonates.","authors":"Hannawayya, Rita; Puentes, Rodrigo; Mirzadzare, Niloofar; Cirone, Karina; Amin, Harish; Soraisham, Amuchou; Alshaikh, Belal; Thomas, Sumesh; Cobo, Eduardo R","year":2025,"journal":"Pediatric research, 98(1), 278-285","doi":"10.1038/s41390-025-03882-9","pmid":"39856229","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11288","title":"Efficacy and safety of tirzepatide in children and adolescents with type 2 diabetes (SURPASS-PEDS): a randomised, double-blind, placebo-controlled, phase 3 trial.","authors":"Hannon, Tamara S; Chao, Lily C; Barrientos-Pérez, Margarita; Pamidipati, Karthik Chandrasekhar; Landó, Laura Fernández; Lee, Clare J; Patel, Hiren; Bergman, Brandon K","year":2025,"journal":"Lancet (London, England), 406(10511), 1484-1496","doi":"10.1016/S0140-6736(25)01774-X","pmid":"40975112","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11289","title":"Calcitonin gene-related peptide in newly diagnosed idiopathic intracranial hypertension: a prospective, cross-sectional, case-control study of cerebrospinal fluid and plasma.","authors":"Hansen, Nadja Skadkær; Korsbaek, Johanne Juhl; Bak, Lasse Kristoffer; Jørgensen, Niklas Rye; Beier, Dagmar; Jensen, Rigmor Højland","year":2025,"journal":"The journal of headache and pain, 26(1), 95","doi":"10.1186/s10194-025-02042-y","pmid":"40301724","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CGRP levels in both plasma and cerebrospinal fluid were not elevated in patients with idiopathic intracranial hypertension (IIH) compared to headache controls or healthy controls. No differences were found after adjusting for BMI, age, and smoking. CGRP levels were not associated with having migraine-like headache, chronic headache, or any headache versus no headache in IIH patients. However, plasma CGRP correlated significantly with CSF CGRP levels (p<0.0001). The results suggest basal CGRP levels do not differ in IIH, though the role of CGRP in IIH headache remains unclear.","whyItMatters":"Headache in IIH is often migraine-like, which raised the question of whether CGRP — the key peptide target in modern migraine treatment — might also be elevated in IIH. This well-designed study found no evidence of elevated basal CGRP, suggesting the headache mechanism in IIH may differ from migraine. However, the authors note that anti-CGRP therapy in IIH remains an unexplored area that could still be beneficial regardless of basal levels.","specificNumbers":"97 IIH patients · 52 non-IIH headache controls · 37 healthy controls · no difference in plasma CGRP (p=0.78) · no difference in CSF CGRP (p=0.79) · plasma-CSF CGRP correlation (p<0.0001)","methodology":"This prospective, cross-sectional, case-control study enrolled patients at two Danish tertiary headache centers. Participants included 97 newly diagnosed IIH patients, 52 non-IIH headache controls, and 37 sex-, age-, and BMI-matched healthy controls. CGRP was measured in both plasma and cerebrospinal fluid using a validated radioimmunoassay. CSF:plasma ratios were calculated. Statistical comparisons used ANOVA/Kruskal-Wallis tests with regression adjustments for confounders.","limitations":"The study measured basal resting CGRP levels, which may not reflect CGRP release during active headache episodes. CGRP levels could still be elevated during headache attacks even if baseline levels are normal. The cross-sectional design provides only a snapshot. The radioimmunoassay methodology may not capture all CGRP isoforms relevant to headache pathology."},{"rthcId":"RPEP-11290","title":"Glucose-dependent insulinotropic polypeptide receptor signaling in oligodendrocytes increases the weight-loss action of GLP-1R agonism.","authors":"Hansford, Robert; Buller, Sophie; Tsang, Anthony H; Benoit, Simon; Roberts, Anna G; Erskine, Emmy; Brown, Thomas; Pirro, Valentina; Reimann, Frank; Harada, Norio; Inagaki, Nobuya; Samms, Ricardo J; Broichhagen, Johannes; Hodson, David J; Adriaenssens, Alice; Park, Soyoung; Blouet, Clemence","year":2025,"journal":"Cell metabolism, 37(9), 1820-1834.e5","doi":"10.1016/j.cmet.2025.07.009","pmid":"40812310","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11291","title":"The Antimicrobial and Host Defense Peptides of Drosophila melanogaster.","authors":"Hanson, Mark A; Westlake, Hannah E; Bulet, Philippe; Lemaitre, Bruno","year":2025,"journal":"Annual review of microbiology, 79(1), 335-360","doi":"10.1146/annurev-micro-101923-100221","pmid":"41130919","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11292","title":"Utilization Trends of Dual GIP/GLP-1 Receptor Agonist, Newer Glucose-Lowering Medications, and Anti-Obesity Medications Among Patients With Chronic Kidney Disease With and Without Type 2 Diabetes.","authors":"Hansrivijit, Panupong; Ortega-Montiel, Janinne; Wexler, Deborah J; Patorno, Elisabetta; Paik, Julie M","year":2025,"journal":"Kidney medicine, 7(6), 101013","doi":"10.1016/j.xkme.2025.101013","pmid":"40510603","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11293","title":"Comparative evaluation of antimicrobial peptides: effect on formation, metabolic activity and viability of Klebsiella pneumoniae biofilms.","authors":"Hanstein, Sophia; Grochow, Thomas; Mötzing, Marina; Fietz, Simone A; Hoffmann, Ralf; Baums, Christoph G; Kähl, Sophie","year":2025,"journal":"Frontiers in microbiology, 16, 1548362","doi":"10.3389/fmicb.2025.1548362","pmid":"40291808","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11294","title":"Quantum Mechanics/Molecular Mechanics Simulations Distinguish Insulin-Regulated Aminopeptidase Substrate (Oxytocin) and Inhibitor (Angiotensin IV) and Reveal Determinants of Activity and Inhibition.","authors":"Hanževački, Marko; Twidale, Rebecca M; Lang, Eric J M; Gerrard, Will; Wright, David W; Stojevic, Vid; Mulholland, Adrian J","year":2025,"journal":"Journal of chemical information and modeling, 65(12), 6261-6272","doi":"10.1021/acs.jcim.5c00869","pmid":"40495656","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11295","title":"Effect of enhanced external counterpulsation on the rehabilitation of patients with acute myocardial infarction after drug-coated balloon-based percutaneous coronary intervention.","authors":"Hao, Xiaojiao; Zhang, Yan; Huang, Damin; Gu, Wenxi; Lu, Yingmin","year":2025,"journal":"Journal of cardiothoracic surgery, 20(1), 210","doi":"10.1186/s13019-024-03230-8","pmid":"40251618","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11296","title":"De Novo Design of Highly Stable Binders Targeting Dihydrofolate Reductase in Klebsiella pneumoniae.","authors":"Haq, Ihteshamul; Anwar, Faheem; Tong, Yigang","year":2025,"journal":"Proteins, 93(10), 1675-1687","doi":"10.1002/prot.26835","pmid":"40371895","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11297","title":"In Silico Binding Mode Analysis of Blarina Paralytic Peptides with the Human T-Type Ca Channel hCav3.2.","authors":"Hara, Nozomi; Sadamoto, Chihiro; Fukuoka, Ryo; Yano, Yusuke; Maturana, Andres D; Kita, Masaki","year":2025,"journal":"Toxins, 17(11)","doi":"10.3390/toxins17110549","pmid":"41295864","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11298","title":"Sex-Specific Association Between Calcium-Channel Blocker Use and B-Type Natriuretic Peptide Levels in Elderly Hypertensive Patients With Heart Failure With Preserved Ejection Fraction.","authors":"Harada, Eisaku; Yamada, Toshihiro; Mizuno, Yuji; Arima, Yuichiro; Kikuta, Koichi; Yasue, Hirofumi","year":2025,"journal":"Circulation journal : official journal of the Japanese Circulation Society, 89(10), 1719-1721","doi":"10.1253/circj.CJ-25-0404","pmid":"40603083","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11299","title":"Identification of Novel TAT-I24-Related Peptides with Antiviral Activities.","authors":"Harant, Hanna; Höfinger, Siegfried; Grabherr, Reingard; Ruzsics, Zsolt; Hengel, Hartmut","year":2025,"journal":"International journal of molecular sciences, 26(23)","doi":"10.3390/ijms262311433","pmid":"41373588","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11300","title":"Liraglutide and denatonium benzoate attenuate T2DM-induced metabolic, neurological, and testicular changes in rats: Targeting oxidative stress, inflammation, and BCRP transporter.","authors":"Harby, Sahar A; Fathelbab, Mona Hassan; Nawwar, Basma M; Sheta, Eman; Halwag, Dalia Ibrahim; Elneily, Dalia Abd Elmoaty; Habiba, Esraa S","year":2025,"journal":"Journal of molecular histology, 56(2), 78","doi":"10.1007/s10735-025-10355-0","pmid":"39881033","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11301","title":"Glucagon-Like Peptide-1 Receptor Agonist Treatment and Risk of Esophageal Cancer.","authors":"Hardvik Åkerström, Johan; Santoni, Giola; von Euler-Chelpin, My; Birgisson, Helgi; Ness-Jensen, Eivind; Kauppila, Joonas H; Holmberg, Dag; Lagergren, Jesper","year":2025,"journal":"The American journal of gastroenterology","doi":"10.14309/ajg.0000000000003885","pmid":"41384845","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11302","title":"Synthetic host defense peptide inhibits SARS-CoV-2 replication in vitro.","authors":"Harfoot, Rhodri; Lawley, Blair; Hernández, Leonor C; Kuang, Joanna; Hills, Francesca R; Sinha, Shubhra; Allais, Margot J M; Bird, Tom W; Hird, Cody P; Taylor, John A; Bostina, Mihnea; Comoletti, Davide; Haney, Evan F; Hancock, Robert E W; Pletzer, Daniel; Quiñones-Mateu, Miguel E","year":2025,"journal":"Antimicrobial agents and chemotherapy, 69(8), e0170024","doi":"10.1128/aac.01700-24","pmid":"40548715","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11303","title":"Is semaglutide cost-effective at closing the gap for Aboriginal and Torres Strait Islander Australians with cardiovascular disease and obesity without type 2 diabetes?","authors":"Hargovan, Satyen; Hunt, Nadine; Kostakis, Hara; Chow, Clara K","year":2025,"journal":"Internal medicine journal, 55(10), 1725-1732","doi":"10.1111/imj.70160","pmid":"40693572","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In a 25-year Markov model of 13,650 Aboriginal and Torres Strait Islander Australians with cardiovascular disease and obesity (without type 2 diabetes), semaglutide was projected to prevent 929 additional fatal CVD events and 13,480 non-fatal CVD events compared to standard care. The program would save 8,628 disability-adjusted life years at an additional cost of approximately $26 million per year to the Australian government — less than 0.2% of annual CVD expenditure. The incremental cost-effectiveness ratio was $75,206/DALY.","whyItMatters":"Indigenous Australians experience a disproportionate burden of cardiovascular disease that is largely preventable. This study provides health-economic evidence that could support policy decisions to fund semaglutide for this underserved population, potentially addressing a significant health equity gap at a cost that falls within acceptable thresholds.","specificNumbers":"","methodology":"The researchers built a Markov cohort state-transition model that cycled annually over 25 years. The target population was Aboriginal and Torres Strait Islander Australians with cardiovascular disease and obesity without type 2 diabetes, receiving either semaglutide or standard care. Transition probabilities, utilities, costs, and discount rates were derived from published literature including the SELECT trial. Sensitivity analyses tested various scenarios.","limitations":"This is a modeling study, not a clinical trial, so results depend on assumptions about transition probabilities and costs. The SELECT trial population may not perfectly represent Indigenous Australians. The model assumes full adherence to semaglutide over 25 years, which is unrealistic in practice. Cultural and access barriers to medication use in remote communities were not modeled. Drug pricing may change over time."},{"rthcId":"RPEP-11304","title":"Low serum 25-hydroxyvitamin D levels in migraine are not related to headache frequency: A case-control study in patients with high-frequency/chronic migraine.","authors":"Haro, Marina; Gárate, Gabriel; Hernández, José Luis; Olmos, José Manuel; Muñoz, María; González-Quintanilla, Vicente; Pascual, Julio","year":2025,"journal":"Headache, 65(5), 863-870","doi":"10.1111/head.14901","pmid":"39803802","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11305","title":"Glucagon-like Peptide-1 (GLP-1) Receptor Agonists and Cancer Prevention: Methodological Pitfalls in Observational Studies.","authors":"Harris, Matthew; Harvie, Michelle; Renehan, Andrew G","year":2025,"journal":"Cancers, 17(9)","doi":"10.3390/cancers17091451","pmid":"40361378","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11306","title":"Brown Adipose Tissue Mimicking Head and Neck Cancer on PET Scan in a Patient on GLP-1 Drug.","authors":"Harrison, Daron B; Phillips, Alisa L; Tansey, James B; Clarke, Travis J; Wood, C B; Nedzi, Lucien; Schwartz, David L; Makowski, Liza; Hayes, D N; Newman, Grace; Gleysteen, John P","year":2025,"journal":"The Laryngoscope, 135(2), 741-743","doi":"10.1002/lary.31815","pmid":"39370986","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In a 61-year-old female with Class III obesity who had lost significant weight on semaglutide, PET/CT imaging showed FDG uptake in a right level II lymph node consistent with her known neck mass. However, the scan also revealed extensive brown adipose tissue (BAT) activation throughout the cervical and supraclavicular regions and mediastinum, which mimicked diffuse regional metastasis.\n\nCareful fusion of anatomical CT data with functional PET data was required to distinguish metabolically active brown fat from malignant disease. Without this careful interpretation, the brown fat activation could have led to misdiagnosis of widespread cancer and unnecessary aggressive treatment.","whyItMatters":"With tens of millions of people now using GLP-1 receptor agonists like semaglutide, radiologists and oncologists need to be aware that these drugs can activate brown fat in ways that confound cancer imaging. PET/CT is a cornerstone of cancer staging and surveillance, and false positives from GLP-1-activated brown fat could lead to unnecessary biopsies, delayed treatment, or overtreatment. This case is among the first to formally document this diagnostic interaction.","specificNumbers":"","methodology":"This is a clinical case report documenting a single patient encounter at a medical center. The case describes a 61-year-old female on semaglutide who presented with a right-sided neck mass. Diagnostic workup included PET/CT imaging, with detailed analysis of FDG uptake patterns to differentiate brown adipose tissue activation from malignant disease.","limitations":"This is a single case report, which provides the lowest level of clinical evidence. It describes one patient's experience and cannot establish how frequently this diagnostic confusion occurs across the broader population of GLP-1RA users. The case does not include data on how commonly brown fat activation causes diagnostic challenges in other patients on semaglutide or other GLP-1 drugs."},{"rthcId":"RPEP-11307","title":"Effect of pemvidutide, a GLP-1/glucagon dual receptor agonist, on MASLD: A randomized, double-blind, placebo-controlled study.","authors":"Harrison, Stephen A; Browne, Sarah K; Suschak, John J; Tomah, Shaheen; Gutierrez, Julio A; Yang, Jay; Roberts, M Scot; Harris, M Scott","year":2025,"journal":"Journal of hepatology, 82(1), 7-17","doi":"10.1016/j.jhep.2024.07.006","pmid":"39002641","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11308","title":"Safety and Efficacy of Efruxifermin in Combination With a GLP-1 Receptor Agonist in Patients With NASH/MASH and Type 2 Diabetes in a Randomized Phase 2 Study.","authors":"Harrison, Stephen A; Frias, Juan P; Lucas, K Jean; Reiss, Gary; Neff, Guy; Bollepalli, Sureka; Su, Yan; Chan, Doreen; Tillman, Erik J; Moulton, Ali; de Temple, Brittany; Zari, Arian; Shringarpure, Reshma; Rolph, Timothy; Cheng, Andrew; Yale, Kitty","year":2025,"journal":"Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, 23(1), 103-113","doi":"10.1016/j.cgh.2024.02.022","pmid":"38447814","tags":["glp-1-agonists","liver-disease","combination-therapy"],"studyType":"Randomized Controlled Trial (Phase 2b)","evidenceStrength":"Moderate","keyFinding":"Adding efruxifermin (an FGF21 analog) to GLP-1 receptor agonist therapy in patients with MASH, liver fibrosis, and type 2 diabetes produced dramatic liver fat reduction: 65% decrease in hepatic fat fraction compared to just 10% with GLP-1 RA alone over 12 weeks (P < .0001). The combination also improved markers of liver injury, fibrosis, glucose metabolism, and lipid levels while maintaining the weight loss benefits of the GLP-1 RA.\n\nSafety was a key focus: the combination appeared well-tolerated with a safety profile comparable to either drug alone. The most common side effects were mild-to-moderate GI events. Only one patient discontinued due to nausea, and there were no treatment-related serious adverse events. Nearly half the patients were on semaglutide, with the remainder on dulaglutide or liraglutide.","whyItMatters":"MASH (formerly NASH) affects millions of people worldwide and is closely tied to obesity and type 2 diabetes — the same patients increasingly being treated with GLP-1 drugs. While GLP-1 RAs provide modest liver benefits through weight loss, this study shows that adding efruxifermin dramatically amplifies liver fat reduction beyond what GLP-1 drugs achieve alone. This combination approach could be critical because MASH is becoming the leading cause of liver transplants, and effective combination therapies are urgently needed.","specificNumbers":"n=31 · 2:1 randomization · efruxifermin 50 mg weekly · 12 weeks · HFF reduced 65% vs 10% placebo · P<.0001 · 48.4% on semaglutide · 45.2% on dulaglutide · 6.5% on liraglutide · 1 discontinuation (nausea) · 0 serious AEs","methodology":"Double-blind, placebo-controlled phase 2b trial (Cohort D). Adults with type 2 diabetes and biopsy-confirmed MASH with fibrosis (F1-F3) on stable GLP-1 RA therapy were randomized 2:1 to receive efruxifermin 50 mg or placebo weekly for 12 weeks. Primary endpoint was safety/tolerability. Secondary endpoints included hepatic fat fraction (measured by MRI), liver injury biomarkers, fibrosis markers, and metabolic parameters.","limitations":"Small sample size (31 patients) limits statistical power for secondary endpoints. The 12-week duration is too short to assess fibrosis reversal on histology (biopsy). No liver biopsies were performed post-treatment — fibrosis changes were assessed by non-invasive markers only. The study was not powered to detect differences in clinical outcomes. The GLP-1 RA background varied (semaglutide, dulaglutide, liraglutide), making it difficult to determine if the combination works differently with different GLP-1 drugs."},{"rthcId":"RPEP-11309","title":"Consistent improvements in liver histology across subgroups in a post hoc analysis of the SYNERGY-NASH trial with tirzepatide.","authors":"Hartman, Mark L; Loomba, Rohit; Lawitz, Eric J; Vuppalanchi, Raj; Boursier, Jérôme; Bugianesi, Elisabetta; Yoneda, Masato; Tang, Yuanyuan; Brouwers, Bram; Bunck, Mathijs C; Haupt, Axel; Sanyal, Arun J","year":2025,"journal":"JHEP reports : innovation in hepatology, 7(8), 101472","doi":"10.1016/j.jhepr.2025.101472","pmid":"40689147","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11310","title":"Type 2 Diabetes Mellitus Diagnosed at the Age of Eight Years: A Case Report.","authors":"Hasan, Md Rakibul; Hasan, Mashfiqul; Aharama, Al","year":2025,"journal":"Cureus, 17(5), e85065","doi":"10.7759/cureus.85065","pmid":"40585621","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11311","title":"Cardiovascular risk reduction with glucagon-like peptide-1 receptor agonists is proportional to HbA1c lowering in type 2 diabetes: An updated meta-regression analysis incorporating FLOW and SOUL trials.","authors":"Hasebe, Masashi; Su, Chen-Yang; Keidai, Yamato; Minamino, Hiroto; Yabe, Daisuke; Inagaki, Nobuya; Yoshiji, Satoshi","year":2025,"journal":"Diabetes, obesity & metabolism, 27(12), 7210-7220","doi":"10.1111/dom.70121","pmid":"40926380","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11312","title":"Unveiling the efficacy and safety of Erenumab, a monoclonal antibody targeting calcitonin gene-related peptide (CGRP) receptor, in patients with chronic and episodic migraine: a GRADE-assessed systematic review and meta-analysis of randomized clinical trials with subgroup analysis.","authors":"Haseeb, Mohamed E; Mohammed, Hazem E; Yaser, Hatem; Hanen, George; Nasser, Mohamed; Yaser, Shehab; Bady, Zeyad","year":2025,"journal":"Head & face medicine, 21(1), 19","doi":"10.1186/s13005-025-00494-w","pmid":"40134001","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"At three months, erenumab produced statistically significant improvements across all outcomes: monthly migraine days reduced by 1.78 (95% CI: -2.37 to -1.20, P < 0.00001), monthly medication days reduced by 1.36 (95% CI: -1.92 to -0.81, P < 0.00001), HIT-6 headache impact score improved by 2.83 points (95% CI: -3.83 to -1.82, P < 0.00001), and 52% more patients achieved ≥50% reduction in migraine days (RR: 1.52, 95% CI: 1.31 to 1.76, P < 0.00001). Subgroup analysis showed greater efficacy in patients with prior treatment failures. No significant difference between 70 mg and 140 mg doses except for medication day reduction.","whyItMatters":"Migraine affects 14% of the global population, and many patients don't respond well to traditional preventives (beta-blockers, antidepressants, anticonvulsants). This meta-analysis provides the strongest pooled evidence to date that erenumab — which specifically targets the CGRP peptide pathway involved in migraine — offers consistent relief with minimal side effects. The finding that it works best for patients who've failed other treatments is especially important, as these are the patients with the most unmet need.","specificNumbers":"","methodology":"Systematic review and meta-analysis of 20 randomized controlled trials (n=5,212) identified from six electronic databases through July 2024. Analysis used Review Manager 5.4 with weighted mean difference for continuous outcomes and risk ratio for dichotomous outcomes. Subgroup analyses were performed by migraine type (episodic vs. chronic), dose (70 mg vs. 140 mg), and prior treatment failure status. Evidence quality was assessed using GRADE methodology. Registered on PROSPERO (CRD42024573300).","limitations":"The 3-month follow-up may not capture long-term efficacy or safety. Individual trial populations and designs varied, which could introduce heterogeneity. The subgroup finding of greater benefit in treatment-failure patients could reflect regression to the mean or selection effects. Publication bias cannot be entirely excluded. The analysis doesn't compare erenumab head-to-head against other CGRP antibodies."},{"rthcId":"RPEP-11313","title":"SSTR-directed peptide receptor radionuclide therapy for recurrent meningiomas: analysis of safety, efficacy and prognostic factors.","authors":"Hasenauer, Natalie; Müller, Miriam; Hänscheid, Heribert; Serfling, Sebastian E; Michalski, Kerstin; Heinrich, Marieke; Polat, Bülent; Buck, Andreas K; Werner, Rudolf A; Hartrampf, Philipp E","year":2025,"journal":"European journal of nuclear medicine and molecular imaging, 53(1), 116-127","doi":"10.1007/s00259-025-07336-6","pmid":"40455253","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11314","title":"Once-Weekly Semaglutide Versus Once-Daily Liraglutide for Weight Loss in Adults: A Meta-Analysis of Randomized Controlled Trials.","authors":"Hashmi, Tallal Mushtaq; Ahmed, Mushood; Haider, Ali; Naseem, Salman; Jafar, Uzair; Hussain, Munir; Iqbal, Javed; Ali, Waqar; Ahmed, Raheel","year":2025,"journal":"Clinical and translational science, 18(2), e70127","doi":"10.1111/cts.70127","pmid":"39930946","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 3 RCTs with 922 patients, once-weekly semaglutide versus once-daily liraglutide produced: significantly greater weight loss (WMD -4.55 kg, 95% CI -6.43 to -2.67, p<0.01), greater HbA1c reduction (WMD -0.46%, 95% CI -0.84 to -0.08, p=0.02), and greater fasting plasma glucose reduction (WMD -1.23 mmol/L, 95% CI -1.51 to -0.95, p<0.01). Safety was comparable: severe adverse events (OR 1.66, p=0.38) and GI adverse events (OR 1.84, p=0.14) did not significantly differ between groups.","whyItMatters":"Semaglutide and liraglutide are both widely prescribed GLP-1 drugs, but many patients and clinicians wonder which is better. This meta-analysis provides clear evidence that semaglutide delivers superior weight and glycemic outcomes with the convenience of weekly dosing, helping inform one of the most common prescribing decisions in diabetes and obesity care.","specificNumbers":"","methodology":"Systematic review and meta-analysis of randomized controlled trials from Cochrane Library, PubMed, and ScienceDirect through July 2024. Three RCTs comparing once-weekly semaglutide to once-daily liraglutide were included. Analysis used R version 4.4.1 with a random effects model to account for between-study variability.","limitations":"Only 3 RCTs with 922 total patients were available, which is a relatively small evidence base for a meta-analysis. The specific semaglutide and liraglutide doses compared may have varied across trials. A random effects model was appropriately used, but heterogeneity across studies may still affect results. The analysis focused on diabetes patients and may not fully generalize to weight management in non-diabetic populations."},{"rthcId":"RPEP-11315","title":"Casuarinin modulates renin-angiotensin-aldosterone system to counter ephedrine-induced myocardial damage in rats.","authors":"Hassan, Hesham M; Hayat, Muhammad Faisal; Akbar, Ali; Zafar, Azka; Alzahrani, Khalid J; Alzahrani, Fuad M; Aljohani, Abrar","year":2025,"journal":"Toxicon : official journal of the International Society on Toxinology, 266, 108522","doi":"10.1016/j.toxicon.2025.108522","pmid":"40780307","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11316","title":"Melanoxetin modulates oxidative, inflammatory and apoptotic pathways to confer cardio-protection against flumethrin-induced sub-chronic toxicity.","authors":"Hassan, Hesham M; Bibi, Aqsa; Antoniolli, Giorgio; El Safadi, Mahmoud; Alzahrani, Khalid J; Alzahrani, Fuad M; Aljohani, Abrar; Ali, Adnan","year":2025,"journal":"Toxicon : official journal of the International Society on Toxinology, 267, 108580","doi":"10.1016/j.toxicon.2025.108580","pmid":"40939920","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11317","title":"Tirzepatide gains US Food and Drug Administration approval for the management of obstructive sleep apnea: Implications for oral health care providers.","authors":"Hassan, Mohamed G; Hassan, Dina G; Hassan, Gamaleldin A","year":2025,"journal":"Journal of the American Dental Association (1939), 156(8), 620-625","doi":"10.1016/j.adaj.2025.05.007","pmid":"40569229","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tirzepatide received FDA approval in 2024 for managing obesity in adults with obstructive sleep apnea. The dual GIP/GLP-1 receptor agonist works by promoting weight loss, which reduces the breathing interruptions characteristic of OSA and enhances sleep quality.\n\nThe review highlights that tirzepatide has potential implications for oral health, including the management of periodontal disease, dental implant procedures, and orthodontic interventions. Dental care providers should understand these connections as part of multidisciplinary OSA management that combines lifestyle modifications, pharmaceutical interventions, oral appliance therapy, and surgical options.","whyItMatters":"Obstructive sleep apnea increases the risk of heart disease, stroke, and other serious conditions, and affects millions of adults — many of whom are undiagnosed. Tirzepatide's approval for OSA represents the first peptide-based pharmaceutical treatment for this condition, offering a new tool alongside CPAP machines and oral appliances. The connection to dental care is significant because dentists are often the first healthcare providers to notice signs of OSA during routine examinations.","specificNumbers":"","methodology":"The authors conducted a comprehensive MEDLINE literature search and reviewed original research articles and systematic reviews related to obstructive sleep apnea and tirzepatide. This is a narrative review aimed at informing dental practitioners about the drug's implications for oral health care.","limitations":"This is a narrative review, not original research. The article is written for a dental audience and does not present new clinical data. The specific degree of OSA improvement with tirzepatide is not quantified in the abstract. Long-term effects of tirzepatide on oral health conditions are speculative. The review does not address cost, access, or insurance coverage considerations."},{"rthcId":"RPEP-11318","title":"Linking GLP-1 activation with steroidogenesis, redox, endoplasmic reticulum stress, mitophagy, and the apoptotic regulatory network unlocks the emerging impacts of semaglutide on 5-fluorouracil-induced testicular toxicity.","authors":"Hassan, Noha F; Khidr, Haneen Y; Eltelbany, Rania Farag A; Abd El-Galil, Mona M; Reda, Enji; El-Zohairy, Nahla A; Gowifel, Ayah M H","year":2025,"journal":"Life sciences, 381, 124014","doi":"10.1016/j.lfs.2025.124014","pmid":"41072890","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11319","title":"O-SEMA-FAST: A Prospective, Non-interventional Study Investigating Oral Semaglutide Use in Adults with Type 2 Diabetes Mellitus During Ramadan.","authors":"Hassanein, Mohamed; Alawadi, Fatheya; AlKadhim, Ibrahim; Aly, Hazem; Bajawi, Dalila; Cinar, Tarhan; Dhanwal, Dinesh; Jabbar, Abdul; Khader, Said; Khudadah, Khaled; Muzaffar, Talal; Ngome, Mary; Nafach, Jalal; Shaghouli, Amna","year":2025,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 16(4), 663-684","doi":"10.1007/s13300-025-01702-1","pmid":"40016571","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11320","title":"Association between socioeconomic factors and semaglutide use for weight loss: a population-based cross-sectional study in Denmark.","authors":"Hasselbalch, Rasmus Bo; Andrea, Mille Kyhn; Nolsøe, Carl Villaro; Hindborg, Mathias; Yazdanfard, Puriya Daniel Würtz; Sørensen, Kathrine Kold; Blomberg, Stig Nikolaj Fasmer; Christensen, Helle Collatz; Graff, Claus; Denholt, Cæcilie Stilling; Afzal, Shoaib; Nordestgaard, Børge G; Kragholm, Kristian; Bundgaard, Henning; Iversen, Kasper Karmark; Torp-Pedersen, Christian; Andersen, Mikkel Porsborg","year":2025,"journal":"The Lancet regional health. Europe, 56, 101398","doi":"10.1016/j.lanepe.2025.101398","pmid":"41624087","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11321","title":"Heart failure monitoring with a single‑lead electrocardiogram at home.","authors":"Hasumi, Eriko; Fujiu, Katsuhito; Chen, Ying; Miyamoto, Sumie; Oida, Mitsunori; Shimizu, Yu; Kani, Kunihiro; Goto, Kohsaku; Uchida, Ryoko; Liu, Yuxiang; Oshima, Tsukasa; Matsuda, Jun; Matsubara, Takumi J; Sugita, Junichi; Nakayama, Yukiteru; Oguri, Gaku; Kojima, Toshiya; Maru, Yujin; Kodera, Satoshi; Akazawa, Hiroshi; Shoda, Morio; Komuro, Issei","year":2025,"journal":"International journal of cardiology, 432, 133203","doi":"10.1016/j.ijcard.2025.133203","pmid":"40280823","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11322","title":"Efficient nose-to-brain delivery of nine residues peptide (JAL-TA9) exhibiting hydrolytic activity against amyloid-β.","authors":"Hatakawa, Yusuke; Tanaka, Akiko; Furubayashi, Tomoyuki; Katsumi, Hidemasa; Nakamura, Rina; Konishi, Motomi; Akizawa, Toshifumi; Sakane, Toshiyasu","year":2025,"journal":"European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 208, 114661","doi":"10.1016/j.ejpb.2025.114661","pmid":"39914573","tags":["peptide-delivery","neuroprotective-peptides"],"studyType":"Preclinical Pharmacokinetics Study (Rat/Mouse)","evidenceStrength":"early-stage","keyFinding":"A small peptide (JAL-TA9) that can break down amyloid-beta — the toxic protein in Alzheimer's disease — successfully reaches the brain when delivered through the nose, but not when injected into the bloodstream. After nasal administration in rats, the peptide was detectable in cerebrospinal fluid at 0.115 μg/mL within 10 minutes, while IV injection produced undetectable brain levels.\n\nThe peptide has an extraordinarily short blood half-life (<1 minute), making IV delivery useless. But it's far more stable in cerebrospinal fluid than in blood, making the nose-to-brain route ideal. Brain distribution data showed the peptide first reaches the olfactory bulb (peak at 5 min), then moves sequentially to frontal brain (30 min) and occipital brain (60 min), confirming direct nose-to-brain transport.","whyItMatters":"One of the biggest challenges in Alzheimer's drug development is getting peptide therapeutics across the blood-brain barrier. This study elegantly solves that problem: by sniffing the peptide, it travels directly from the nasal cavity along the olfactory nerve into the brain — bypassing the blood entirely. Combined with the peptide's ability to actually degrade amyloid-beta plaques, this represents a two-in-one breakthrough: a therapeutic peptide and a viable delivery route.","specificNumbers":"9-amino acid peptide (YKGSGFRMI) · CSF level: 0.115 μg/mL at 10 min (nasal) vs undetectable (IV) · blood half-life: <1 min · olfactory bulb peak: 5 min · frontal brain: 30 min · occipital brain: 60 min","methodology":"Pharmacokinetic study in rats and mice. IV injection was performed to measure plasma clearance. Stability was tested in plasma, whole blood, and CSF in vitro. Nasal and systemic (IV in rats, intraperitoneal in mice) administration were compared by measuring peptide concentrations in CSF and brain regions over time using validated analytical methods.","limitations":"Animal study only — nasal anatomy and olfactory pathway differ between rodents and humans. No efficacy testing (amyloid plaque clearance) was performed in vivo — only delivery was measured. The peptide's amyloid-cleaving activity was previously demonstrated but not confirmed in this delivery context. Human nasal delivery efficiency is typically lower than in rodents. Long-term safety and tolerability of repeated nasal dosing were not assessed."},{"rthcId":"RPEP-11323","title":"N-terminal pro-B-type natriuretic peptide levels in pregnant women with heart disease and complications: A cohort study.","authors":"Hatamian, Zahra; Vahed, Seyede Houra Mousavi; Vakilian, Farveh; Poorzand, Hoorak; Lotfalizade, Marzieh; Zirak, Nahid; Majd, Hassan Mehrad; Nozari, Marzieh; Dadgar, Salmeh; Afiat, Malihe","year":2025,"journal":"International journal of reproductive biomedicine, 23(9), 749-758","doi":"10.18502/ijrm.v23i9.20162","pmid":"41306464","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11324","title":"Acute Duodenal Ulcer Perforation Following Tirzepatide Treatment: A Case Report.","authors":"Hayashi, Maho; Hayashi, Koji; Tsujigiwa, Yusuke; Uwafuji, Seiko; Sato, Mamiko; Kobayashi, Yasutaka","year":2025,"journal":"Cureus, 17(3), e80671","doi":"10.7759/cureus.80671","pmid":"40236372","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11325","title":"Epithelial Heparan Sulfate Promotes Staphylococcus aureus Corneal Infection by Inhibiting Cathelicidins.","authors":"Hayashida, Kazutaka; Esko, Jeffrey D; Gallo, Richard D; Liu, Jian; Kao, Winston W-Y; Park, Pyong Woo","year":2025,"journal":"Proteoglycan research, 3(4)","doi":"10.1002/pgr2.70041","pmid":"41551642","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11326","title":"Diabetes and Cardiometabolic Care, Pharmacotherapy, and Patient Outcomes in Two Regional Aboriginal Primary Care Health Centres: Lessons to be Learnt.","authors":"Hayes, Annabelle G; Pearson, Odette; Marathe, Chinmay S; Jesudason, David","year":2025,"journal":"Heart, lung & circulation, 34(10), 1069-1077","doi":"10.1016/j.hlc.2025.06.1019","pmid":"40885604","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11327","title":"The Role of GLP-1 Agonists in Esthetic Medicine: Exploring the Impact of Semaglutide on Body Contouring and Skin Health.","authors":"Haykal, Diala; Hersant, Barbara; Cartier, Hugues; Meningaud, Jean-Paul","year":2025,"journal":"Journal of cosmetic dermatology, 24(2), e16716","doi":"10.1111/jocd.16716","pmid":"39645647","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11328","title":"Effects of liraglutide on the testis of rats with experimental diabetes and ischemia-reperfusion injury.","authors":"Hazir, Sinem; Coskun, Gulfidan; Sencar, Leman; Tuli, Abdullah; Dundar Yenilmez, Ebru; Dağlıoğlu, Yusuf Kenan; Ozgur, Hulya; Polat, Sait","year":2025,"journal":"Biotechnic & histochemistry : official publication of the Biological Stain Commission, 100(6), 371-380","doi":"10.1080/10520295.2025.2537045","pmid":"40757489","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11329","title":"In Vitro Bioactivity of a Recombinant Human Collagen Peptide in a Filler Biomimetic Skin Model.","authors":"He, Chunyan; Wang, Ranran; Zhang, Qiao; Wang, Yehong; Huang, Nan","year":2025,"journal":"Journal of cosmetic dermatology, 24(12), e70592","doi":"10.1111/jocd.70592","pmid":"41384336","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Recombinant human collagen III (rhCol III) peptides significantly upregulated matrix remodeling genes in human fibroblasts, including Collagen types I and III, Elastin, Fibrillin 1, and Hyaluronic acid synthases 1, 2, and 3. In a novel 3D filler biomimetic skin model, the peptides directly bound to the dermal scaffold and demonstrated beneficial effects on both skin layers: improved epidermal regeneration (shown by Ki67 and COL17A1 markers) and enhanced dermal remodeling (FBN1 and glycosaminoglycans).\n\nTranscriptomic analysis revealed the peptides downregulated inflammation, senescence, and apoptosis pathways while upregulating integrin binding and extracellular matrix formation — suggesting mechanisms for skin rejuvenation beyond simple volume filling.","whyItMatters":"Most dermal fillers work by adding volume, but collagen peptide-based fillers could actively stimulate the skin's own repair and rejuvenation processes. This research provides mechanistic evidence that recombinant collagen peptides don't just fill — they actually improve skin biology by boosting collagen production, reducing inflammation, and combating cellular aging.","specificNumbers":"","methodology":"The study used 2D human fibroblast cultures to assess mRNA-level gene expression changes, then developed a novel 3D in vitro filler biomimetic skin model to evaluate tissue-level effects. Tissue morphology, epidermal proliferation and differentiation, and dermal extracellular matrix deposition were assessed. Transcriptomic analysis was performed to identify molecular pathways underlying the observed changes.","limitations":"This was entirely an in vitro study using cell cultures and a 3D skin model. The authors acknowledge a significant gap between their biomimetic model and actual injection in living skin. No human clinical data was presented. The 3D model, while novel, may not capture the full complexity of in vivo skin aging, immune responses, or filler degradation over time."},{"rthcId":"RPEP-11330","title":"Neuro-immune regulation in allergic Diseases: Role of neuropeptides.","authors":"He, Cuiying; Wang, Qian; Gao, Jinyan; Chen, Hongbing; Tong, Ping","year":2025,"journal":"International immunopharmacology, 145, 113771","doi":"10.1016/j.intimp.2024.113771","pmid":"39667047","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11331","title":"Ketotic Hypoglycaemia Following Sleeve Gastrectomy.","authors":"He, Jinwen; Phillips, Liza; Nisbet, Janelle; Morton, Adam","year":2025,"journal":"Clinical endocrinology, 103(1), 45-49","doi":"10.1111/cen.15232","pmid":"40129270","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Two patients developed symptomatic ketotic hypoglycemia after sleeve gastrectomy, characterized by low insulin, low C-peptide, and elevated beta-hydroxybutyrate levels during fasting (at 40 and 65 hours respectively). Morning cortisol and IGF-1 were normal, ruling out adrenal or growth hormone deficiency.\n\nDietary management was inadequate. Treatment with semaglutide resulted in complete resolution of hypoglycemic episodes in one patient and significant reduction in the other. The mechanism likely involves reduced hepatic, renal, or intestinal gluconeogenesis after bariatric surgery, or a possible unmasked inborn error of metabolism.","whyItMatters":"Post-bariatric hypoglycemia is a recognized complication, but it's usually driven by hyperinsulinemia (too much insulin). These cases describe a rare and distinct form — ketotic hypoglycemia with appropriately low insulin — that is poorly understood and doesn't respond to standard dietary approaches. The successful use of semaglutide opens a new treatment option for these patients and raises questions about the metabolic consequences of bariatric surgery.","specificNumbers":"","methodology":"This is a case report describing two patients who developed ketotic hypoglycemia following sleeve gastrectomy. The patients underwent prolonged fasting tests (40 and 65 hours), with measurement of glucose, insulin, C-peptide, beta-hydroxybutyrate, cortisol, and IGF-1. Dietary management was trialed first, followed by semaglutide treatment.","limitations":"This is a case report of only two patients, providing the lowest level of clinical evidence. The mechanism by which semaglutide resolves non-insulin-mediated hypoglycemia is not explained and is somewhat paradoxical, since GLP-1 agonists typically enhance insulin secretion. The fasting durations (40 and 65 hours) are extreme and may not reflect typical daily conditions. Underlying inborn errors of metabolism were not definitively excluded through genetic testing."},{"rthcId":"RPEP-11332","title":"Chemotherapy-Induced Peripheral Neuropathy Impairs Tertiary Dentine Formation: An In Vivo Study.","authors":"He, Jun; Zhan, Chaoning; Lu, Yanli; Chen, Junyang; Yang, Xiaojun; Hou, Jin","year":2025,"journal":"International dental journal, 75(5), 100899","doi":"10.1016/j.identj.2025.100899","pmid":"40651328","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11333","title":"Association between GLP-1 RAs and DPP-4 inhibitors with biliary disorders: pharmacovigilance analysis.","authors":"He, Long; Li, Jinwei; Cheng, Xiong; Luo, Li; Huang, Yilan","year":2025,"journal":"Frontiers in pharmacology, 16, 1509561","doi":"10.3389/fphar.2025.1509561","pmid":"40041492","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 2,215 biliary adverse event reports, 1,709 involved GLP-1 RAs and 506 involved DPP-4 inhibitors. Key reporting odds ratios:\n\n- Semaglutide: ROR 4.06 (95% CI 3.76–4.39) for biliary disorders\n- Liraglutide: ROR 3.88 (95% CI 3.50–4.29)\n- DPP-4 inhibitors overall: ROR 3.09 (95% CI 2.83–3.37)\n- Sitagliptin specifically: ROR 3.46 (95% CI 3.13–3.83)\n\nBoth semaglutide and liraglutide showed significant associations with gallbladder disorders, gallstone disorders, and infectious biliary disorders. Liraglutide, alogliptin, sitagliptin, and linagliptin were also linked to biliary malignant tumors. DPP-4 inhibitors had a higher proportion of serious outcomes (76.88%) compared to GLP-1 RAs (51.55%).","whyItMatters":"With tens of millions of people now taking GLP-1 receptor agonists, even rare adverse effects can affect large numbers of patients. This analysis raises a safety signal that gallbladder and biliary problems may be more common with semaglutide and liraglutide than previously appreciated, warranting clinical awareness.","specificNumbers":"","methodology":"Researchers extracted adverse event reports from the FDA Adverse Event Reporting System (FAERS) between Q1 2013 and Q1 2024 using OpenVigil 2.1. They used four standard signal detection methods (ROR, PRR, BCPNN, and EBGM) to assess whether biliary adverse events were reported more frequently than expected for these drug classes.","limitations":"FAERS data has well-known limitations: it relies on voluntary reporting (under-reporting is common), cannot establish causation, may be influenced by reporting biases (e.g., higher awareness of GLP-1 RA side effects drives more reports), and lacks denominators to calculate true incidence rates. Confounders like obesity itself (a gallstone risk factor) and rapid weight loss cannot be controlled for in this analysis."},{"rthcId":"RPEP-11334","title":"Short-Term Weight Loss Outcomes of 1.0 mg Semaglutide Therapy Initiated 6 Months After Sleeve Gastrectomy.","authors":"He, Mengcheng; Wang, Yu; Hua, Rong; Cao, Chong; Xu, Bo; Shen, Qiwei; Fu, Xiaojian; Shao, Yikai; Yao, Qiyuan","year":2025,"journal":"Obesity (Silver Spring, Md.), 33(11), 2067-2075","doi":"10.1002/oby.70006","pmid":"40964805","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11335","title":"Protease-Resistant Azapeptide GLP-1 Analogue Improves Metabolic Control in Diet-Induced Obesity.","authors":"He, Mingzhu; Cheng, Kai Fan; VanPatten, Sonya; Torres, Marcelo D T; Jabari, Bayan Al; Mughrabi, Ibrahim T; Ballarín-González, Borja; Son, Myoungsun; de la Fuente-Nunez, Cesar; Al-Abed, Yousef","year":2025,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2025.05.09.653092","pmid":"41278761","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The lead azapeptide analogue, AzaA8/R34-GLP-1 (AzaA8), demonstrated resistance to dipeptidyl peptidase-4 (DPP-4) degradation for over 24 hours — a dramatic improvement over native GLP-1 which is degraded within minutes. Despite the backbone modification, AzaA8 maintained picomolar potency at the GLP-1 receptor.\n\nIn lean mice, AzaA8 improved oral glucose tolerance. In high-fat diet-induced obese mice, chronic administration reduced body weight, decreased both leptin and insulin levels, and enhanced glucose handling. No detectable inflammatory adverse effects were observed, supporting the safety profile of this azapeptide approach.","whyItMatters":"Current GLP-1 drugs like semaglutide and liraglutide use various strategies to extend their half-life, but they still require modifications like fatty acid chains or PEGylation. Azapeptide substitution represents an entirely different approach — modifying the peptide backbone itself to resist enzymatic breakdown while preserving biological activity. If this translates to humans, it could lead to a new class of longer-lasting, potentially simpler GLP-1 therapies for diabetes and obesity.","specificNumbers":"","methodology":"Researchers used solid-phase peptide synthesis to create GLP-1 analogues with aza-substitutions (replacing α-carbon with nitrogen) at protease-sensitive residues. They evaluated DPP-4 resistance in vitro, measured GLP-1 receptor signaling potency, and assessed plasma half-life in mice. In vivo efficacy was tested in lean mice (oral glucose tolerance) and in high-fat diet-induced obese mice (chronic administration measuring body weight, glucose handling, insulin, leptin, and inflammatory markers).","limitations":"This is a preprint (bioRxiv) that has not yet undergone peer review. All experiments were conducted in mice, and translation to humans is uncertain. Specific dosing details and exact weight loss percentages were not provided in the abstract. Long-term safety and efficacy data beyond the chronic dosing period are unavailable. The comparison was against unmodified GLP-1, not against approved drugs like semaglutide."},{"rthcId":"RPEP-11336","title":"IGF1 Signaling Regulates Neuropeptide Expression in Hypothalamic Neurons Under Physiological and Pathological Conditions.","authors":"He, Wenyuan; Loganathan, Neruja; Belsham, Denise D","year":2025,"journal":"Endocrinology, 166(5)","doi":"10.1210/endocr/bqaf051","pmid":"40105689","tags":[],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"IGF1 regulates the expression of multiple appetite-controlling neuropeptides in hypothalamic neurons. In both mouse and human models, IGF1 modulated expression of AgRP, NPY, POMC, CART, spexin, galanin, and FAM237B, producing an overall appetite-suppressing (anorexigenic) profile. IGF1 receptors were found in both NPY/AgRP and POMC neurons, with higher expression in POMC neurons.\n\nCritically, the study discovered that hyperinsulinemia (chronically high insulin levels) induces IGF1 resistance in hypothalamic neurons by reducing IGF1R protein and mRNA through over-activation of PI3K-FOXO1 signaling. This provides a novel mechanism linking metabolic disease to disrupted neuropeptide signaling in the brain.","whyItMatters":"Understanding how growth factor signaling regulates appetite-controlling neuropeptides is fundamental to treating obesity and metabolic disease. The discovery that high insulin levels cause IGF1 resistance in the hypothalamus creates a new framework for understanding why metabolic dysfunction leads to appetite dysregulation — and potentially identifies new therapeutic targets.","specificNumbers":"","methodology":"Researchers used RT-qPCR and single-cell RNA sequencing to characterize IGF1 receptor expression in hypothalamic neuron populations. Mouse and human cell models were treated with IGF1 to assess neuropeptide expression changes. The effects of fasting, nutrient availability, and circadian rhythms on IGF1 binding proteins were measured. Hyperinsulinemia conditions were modeled to study IGF1 resistance mechanisms via the PI3K-FOXO1 pathway.","limitations":"This is primarily an in vitro/cell model study. While both mouse and human models were used, the findings need validation in intact animal models and human subjects. The complexity of hypothalamic neuropeptide circuits means that isolated cell responses may not fully predict in vivo outcomes. The hyperinsulinemia-IGF1 resistance mechanism is novel and requires independent confirmation."},{"rthcId":"RPEP-11337","title":"Unraveling the safety profile of GLP-1 receptor agonists: Mechanistic insights with a focus on semaglutide.","authors":"He, Xinyi; Zhao, Zimo; Sun, Yan; Jiang, Xi","year":2025,"journal":"European journal of medicinal chemistry, 300, 118163","doi":"10.1016/j.ejmech.2025.118163","pmid":"40975962","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11338","title":"Brain Insulin Signaling Pathway Regulation of Hippocampal Neuroplasticity in Neurocognitive Disorders: Mechanisms and Therapeutic Implications.","authors":"He, Yanan; Sun, Miao; Qu, Mengyao; Lu, Yixun; Yang, Huikai; Wang, Rui; Li, Yingfu; Li, Peng; Mi, Weidong; Ma, Yulong","year":2025,"journal":"Journal of integrative neuroscience, 24(8), 39446","doi":"10.31083/JIN39446","pmid":"40919624","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11339","title":"Integration of pre-trained GRU and molecular docking for virtual screening of quinoa seed derived ACE inhibitory peptides: An innovative prediction strategy.","authors":"He, Yanan; Deng, Zhiyang; Lyu, Yujiao; Yan, Yan; Liu, Jun; Liu, Haijie","year":2025,"journal":"Food chemistry, 492(Pt 3), 145591","doi":"10.1016/j.foodchem.2025.145591","pmid":"40712418","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The Pre-GRU deep learning model combined with molecular docking successfully identified ACE-inhibitory peptides from quinoa:\n\n- Model accuracy: R²train = 0.86-0.88, R²test = 0.53-0.55\n- 4 out of 7 synthesized candidate peptides showed ACE inhibition activity (57% hit rate)\n- NLFRP was the most potent: IC50 = 3.33 ± 0.19 μM\n- Molecular docking revealed NLFRP forms tetrahedral coordination with ACE's zinc-binding HEXXH motif, explaining its strong binding\n- Transfer learning from adjacent peptide lengths addressed the common problem of limited training data\n- Balanced MSE loss function improved prediction accuracy despite imbalanced datasets","whyItMatters":"Traditional bioactive peptide discovery involves time-consuming trial-and-error experimentation. By using AI to predict which peptides from a food source will have therapeutic activity, researchers can focus synthesis and testing on the most promising candidates — in this case achieving a 57% hit rate (4 of 7). This approach could dramatically accelerate the discovery of food-derived peptides for managing hypertension and other conditions, making functional foods more scientifically targeted.","specificNumbers":"","methodology":"A pretrained Gated Recurrent Unit (GRU) deep learning model was developed using transfer learning — pretraining on known ACE-inhibitory peptides of various lengths, then fine-tuning on quinoa-specific data to overcome limited training samples. The model predicted IC50 values for candidate peptides from germinated quinoa seed protein. Top candidates were further evaluated by molecular docking to simulate ACE binding. Seven top-ranked peptides were synthesized and experimentally tested for ACE inhibition in vitro.","limitations":"The model's test set accuracy (R²=0.53-0.55) is moderate, suggesting room for improvement. Only 7 peptides were synthesized and tested, limiting validation scope. All ACE inhibition data are in vitro — no cell-based, animal, or human blood pressure studies were conducted. The quinoa-derived peptides' stability during digestion and their oral bioavailability were not assessed. The IC50 value, while potent in vitro, does not guarantee in vivo blood pressure-lowering effects."},{"rthcId":"RPEP-11340","title":"Efficacy and safety of cAMP-biased GLP-1 receptor agonist ecnoglutide versus dulaglutide in patients with type 2 diabetes and elevated glucose concentrations on metformin monotherapy (EECOH-2): a 52-week, multicentre, open-label, non-inferiority, randomised, phase 3 trial.","authors":"He, Yang; Mi, Nianrong; Cheng, Zhifeng; Xue, Haibo; Han, Jie; Wang, Haifang; Wang, Huihui; Wu, Jun; Shi, Xiaoguang; Zhao, Shuping; Duan, Binhong; Zhu, Yikun; Zhou, Yanqin; Li, Feng; Wang, Xin; Ling, Hongwei; Wang, Su; Li, Qingju; Jiang, Feifei; Yang, Ming; Bing, Shaohui; Zheng, Qing; Ning, Jing; Guo, Mengying; Bu, Yue; Guan, Lei; Li, Yao; Yang, Liu; Guo, Wanjun; Pan, Hai; Li, Xiaoying","year":2025,"journal":"The lancet. Diabetes & endocrinology, 13(10), 863-873","doi":"10.1016/S2213-8587(25)00196-2","pmid":"40854315","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11341","title":"Effect of Tirzepatide on Heart Failure in Type 2 Diabetes Mellitus and Obesity: A Systematic Review and Meta-Analysis.","authors":"He, Yi-Meng; Zeng, Chen; Zhang, Yu-Fan; Wu, Qi; Zhou, Xiao-Yu; Yan, Pi-Jun; Xu, Yong; Guo, Man; Teng, Fang-Yuan","year":2025,"journal":"Diabetes/metabolism research and reviews, 41(7), e70097","doi":"10.1002/dmrr.70097","pmid":"41100405","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11342","title":"Liraglutide attenuates clozapine-induced mitochondrial dysfunction and improves energy metabolism in the brain of rats.","authors":"He, Yifang; Wang, Liwei; Cao, Ting; Jiao, Shimeng; Chen, Hui; Lin, Chenquan; Guo, Qiujin; He, Feng; Cai, Hualin","year":2025,"journal":"Biochemical pharmacology, 240, 117091","doi":"10.1016/j.bcp.2025.117091","pmid":"40588078","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11343","title":"Liraglutide promotes osteogenic differentiation of mesenchymal stem cells by inhibiting M1 macrophage polarization and CXCL9 release in vitro.","authors":"He, Yilin; Song, Wenpeng; Deng, Yinxin; Lin, Xiao; Gao, Zhenhua; Ma, Pan","year":2025,"journal":"Molecular and cellular endocrinology, 597, 112441","doi":"10.1016/j.mce.2024.112441","pmid":"39706561","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11344","title":"Cerebrospinal Fluid Human Neutrophil Peptides 1-3: A Potential Prognostic Marker in Intracerebral Hemorrhage.","authors":"He, Zhi; Xie, Jun; Yan, Fu-Ling; Geng, Lei-Yu; Zhang, Yue-Xin; Liu, Jing-Jing; Zhang, Chen","year":2025,"journal":"Genetic testing and molecular biomarkers, 29(11), 310-315","doi":"10.1177/19450265251395955","pmid":"41231031","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11345","title":"Obesity and Schizophrenia: Results of a Feasibility Study with Semaglutide to Assist Weight Loss.","authors":"Heald, Adrian H; Reynolds, Gavin; Nash, Isabel; Boyle, Onagh; Daly, Chris; Longson, Damien; O'Shea, Donal; Ingram, Joseph; Holt, Richard; Firth, Joseph; Stedman, Mike; Syed, Akheel; de Hert, Marc","year":2025,"journal":"Advances in therapy, 42(8), 4013-4022","doi":"10.1007/s12325-025-03261-0","pmid":"40536760","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11346","title":"Exacerbation of Postural Orthostatic Tachycardia Syndrome With Tirzepatide Prescribed for Weight Loss.","authors":"Hedge, Eric T; Grappe, Shannon R; Vernino, Steven; Almandoz, Jaime P; Levine, Benjamin D","year":2025,"journal":"JACC. Case reports, 30(32), 105430","doi":"10.1016/j.jaccas.2025.105430","pmid":"40944681","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A 28-year-old woman with obesity and POTS (postural orthostatic tachycardia syndrome) experienced significant worsening of her condition while using tirzepatide for weight loss. Despite having successfully controlled her POTS through exercise training (reducing heart rates to normal values), tirzepatide caused a 20-30 beats/min increase in both supine and standing heart rates — far exceeding the typical ~3 bpm increase seen with GLP-1 drugs. She also experienced recurrence of orthostatic intolerance symptoms.\n\nThis magnitude of heart rate increase with tirzepatide in a POTS patient has not been previously reported.","whyItMatters":"As tirzepatide and other GLP-1/GIP peptide drugs are prescribed to millions of patients for weight loss, clinicians need to understand their effects in patients with coexisting cardiovascular conditions. This case reveals that POTS patients — who already struggle with heart rate dysregulation — may be particularly vulnerable to the heart rate-increasing effects of these peptide drugs, potentially undoing the benefits of established POTS treatments like exercise training.","specificNumbers":"20-30 bpm heart rate increase · vs ~3 bpm typical GLP-1 effect · 28-year-old patient · POTS recurrence · Exercise benefits reversed","methodology":"Single case report from JACC Case Reports. A 28-year-old woman with obesity and POTS was monitored during exercise-based POTS treatment and subsequent tirzepatide therapy. Supine and standing heart rates were measured before and during tirzepatide use. Orthostatic intolerance symptoms were tracked clinically.","limitations":"This is a single case report (n=1) and cannot establish causation or estimate the prevalence of this adverse effect in POTS patients. The patient had pre-existing POTS, so the results may not apply to patients without autonomic disorders. It is unclear whether the effect is specific to tirzepatide or would occur with other GLP-1 agonists. No rechallenge or dose-response data is provided."},{"rthcId":"RPEP-11347","title":"Kidney Parameters with Tirzepatide in Obesity with or without Type 2 Diabetes.","authors":"Heerspink, Hiddo J L; Friedman, Allon N; Bjornstad, Petter; van Raalte, Daniel H; Cherney, David; Cao, Dachuang; Garcia-Pérez, Luis-Emilio; Stefanski, Adam; Turfanda, Ibrahim; Bunck, Mathijs C; Benabbad, Imane; Griffin, Ryan; Piras de Oliveira, Carolina","year":2025,"journal":"Journal of the American Society of Nephrology : JASN, 36(11), 2190-2200","doi":"10.1681/ASN.0000000764","pmid":"40512543","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11348","title":"The Effect of Retatrutide on Kidney Parameters in Participants With Type 2 Diabetes Mellitus and/or Obesity.","authors":"Heerspink, Hiddo J L; Lu, Zeqing; Du, Yu; Duffin, Kevin L; Coskun, Tamer; Haupt, Axel; Hartman, Mark L","year":2025,"journal":"Kidney international reports, 10(6), 1980-1992","doi":"10.1016/j.ekir.2025.03.049","pmid":"40630318","tags":["glp-1-agonists","kidney-disease"],"studyType":"rct-post-hoc","evidenceStrength":"moderate-high","keyFinding":"Retatrutide, the triple-receptor agonist (GIP/GLP-1/glucagon), showed kidney-protective effects in two phase 2 trials. In people with type 2 diabetes, retatrutide 12 mg reduced urine albumin-to-creatinine ratio (UACR) by 37% versus placebo at 36 weeks, though kidney filtration rate (eGFR) was unchanged. In people with obesity but no diabetes, retatrutide 12 mg reduced UACR by 31.5% and increased eGFR by 8.5 ml/min/1.73m² at 48 weeks.\n\nThe eGFR improvement in the obesity group was confirmed using three different measurement methods (creatinine-based, cystatin C-based, and combined), strengthening confidence in the finding. However, since most participants had normal baseline albuminuria, the absolute reductions were modest.","whyItMatters":"Kidney disease is a major complication of both obesity and type 2 diabetes, and current treatments have limited options. This is the first data showing that a triple-agonist peptide (targeting GIP, GLP-1, and glucagon receptors simultaneously) may protect kidneys — not just through weight loss, but potentially through direct renal benefits. If confirmed in dedicated kidney outcome trials, retatrutide could add kidney protection to its weight loss and metabolic benefits.","specificNumbers":"n=619 total · T2D group (n=281): UACR −37% vs placebo at 36 weeks · Obesity group (n=338): UACR −31.5%, eGFR +8.5 ml/min/1.73m² vs placebo at 48 weeks · Dose range: 0.5-12 mg · Baseline eGFR: ~90-91 ml/min/1.73m²","methodology":"Post hoc analysis of two randomized, placebo-controlled phase 2 trials of retatrutide. One enrolled participants with T2D (36 weeks), the other enrolled those with overweight/obesity without T2D (48 weeks). Kidney parameters measured included UACR, eGFR from creatinine, eGFR from cystatin C, and combined eGFR. All participants had baseline eGFR ≥45 ml/min/1.73m². The T2D study included dulaglutide 1.5 mg as an active comparator.","limitations":"Post hoc analysis — kidney outcomes were not the primary endpoint of either trial. Most participants had normal baseline albuminuria, limiting ability to assess effects in people with established kidney disease. Relatively short duration (36-48 weeks). Not powered specifically for kidney endpoints. The eGFR improvement in obesity but not T2D needs explanation."},{"rthcId":"RPEP-11349","title":"Tirzepatide, a dual GIP/GLP1-receptor co-agonist preserves cardiac function and improves survival in angiotensin II-induced heart failure model in mice: comparison to liraglutide.","authors":"Hegedűs, Zsombor I; Jakab, Márk E; Gergely, Tamás G; Sayour, Nabil V; Kovács, Andrea; Antal, Sára; Kovács, Tamás; Ferdinandy, Péter; Varga, Zoltán V; Tóth, Viktória E","year":2025,"journal":"Cardiovascular diabetology, 24(1), 253","doi":"10.1186/s12933-025-02806-5","pmid":"40517248","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11350","title":"Opisthorchis viverrini Helminth Defense Molecule: Structural features, molecular interactions, and dual immunomodulatory roles.","authors":"Heikal, Muhammad Fikri; Kongpha, Kamonrut; Kafle, Alok; Tenorio, Jan Clyden; Chaiyadet, Sujittra; Mahalapbutr, Panupong; Boonloh, Kampeebhorn; Talabnin, Krajang; Laha, Thewarach; Saichua, Prasert; Suttiprapa, Sutas","year":2025,"journal":"Acta tropica, 270, 107809","doi":"10.1016/j.actatropica.2025.107809","pmid":"40882862","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11351","title":"GLP-1 receptor agonists in Parkinson's disease: an updated comprehensive systematic review with meta-analysis.","authors":"Helal, Mohamed Mohsen; AbouShawareb, Hala; Abbas, Omarfayez Hussein; Haddad, Roaa; Zain, Youmna; Osman, Ahmed S A; Hassan, Amr K","year":2025,"journal":"Diabetology & metabolic syndrome, 17(1), 352","doi":"10.1186/s13098-025-01888-1","pmid":"40849485","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Meta-analysis of clinical studies demonstrated that GLP-1 receptor agonists significantly improved motor function in Parkinson's disease:\n\n- MDS-UPDRS Part III (motor examination) in ON state: mean difference = -2.88 points (p=0.01, I²=30%)\n- The low heterogeneity (I²=30%) indicates consistent effects across studies\n- However, GLP-1 RA treatment was associated with higher incidence of adverse events across all safety outcomes\n\nThe review also examined motor complications (Part IV) and motor experiences of daily living (Part II), as well as gastrointestinal and systemic side effects.","whyItMatters":"Parkinson's disease currently has no disease-modifying treatment — all approved therapies only manage symptoms. The finding that GLP-1 receptor agonists improve motor function is significant because these drugs are already FDA-approved, well-characterized, and widely available. If confirmed in larger trials, repurposing GLP-1 drugs for Parkinson's could provide a treatment option far sooner than developing an entirely new drug from scratch.","specificNumbers":"","methodology":"Comprehensive systematic review and meta-analysis following standard methodology. Six databases were searched: PubMed, Scopus, CENTRAL, Web of Science, Embase, and ClinicalTrials.gov. Studies evaluating GLP-1 receptor agonists in Parkinson's disease management were identified and assessed. Primary outcomes included motor impairment (MDS-UPDRS Part III), motor complications (Part IV), motor experiences of daily living (Part II), and safety outcomes. Meta-analysis pooled results across studies.","limitations":"The meta-analysis pooled a limited number of clinical studies, which may affect generalizability. The 2.88-point improvement on MDS-UPDRS Part III, while statistically significant, is modest in clinical terms. Higher adverse event rates raise tolerability concerns. Most studies likely used exenatide or lixisenatide rather than newer agents like semaglutide, which may have different neuroprotective profiles. The duration of follow-up across studies varies, and long-term disease-modifying effects versus symptomatic improvement cannot be distinguished from available data."},{"rthcId":"RPEP-11352","title":"Reaching the SUMMIT? Benefits and potential risks associated with the use of tirzepatide in heart failure with preserved ejection fraction.","authors":"Hellenkamp, Kristian; Sato, Ryosuke; von Haehling, Stephan","year":2025,"journal":"Med (New York, N.Y.), 6(2), 100570","doi":"10.1016/j.medj.2024.12.004","pmid":"39954669","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11353","title":"Once-Weekly Semaglutide in Adults With Alcohol Use Disorder: A Randomized Clinical Trial.","authors":"Hendershot, Christian S; Bremmer, Michael P; Paladino, Michael B; Kostantinis, Georgios; Gilmore, Thomas A; Sullivan, Neil R; Tow, Amanda C; Dermody, Sarah S; Prince, Mark A; Jordan, Robyn; McKee, Sherry A; Fletcher, Paul J; Claus, Eric D; Klein, Klara R","year":2025,"journal":"JAMA psychiatry, 82(4), 395-405","doi":"10.1001/jamapsychiatry.2024.4789","pmid":"39937469","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11354","title":"Documentation of Compounded GLP-1 Receptor Agonists in a Large Primary Care Dataset.","authors":"Hendrix, Nathaniel; Velásquez, Esther E; Pham, Harry; Bazemore, Andrew","year":2025,"journal":"Pharmacoepidemiology and drug safety, 34(10), e70227","doi":"10.1002/pds.70227","pmid":"41024632","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 153,044 patients with documented semaglutide and/or tirzepatide use in the American Family Cohort (a nationwide US primary care EHR database spanning 2021-2024), 8.2% had documented use of compounded formulations. This proportion increased over time as drug shortages drove more patients to compounding pharmacies.\n\nUsers of compounded formulations had notably different demographics: they were more likely to be female, non-Hispanic White, non-diabetic, and living in areas of lower socioeconomic deprivation. They also had longer mean therapy durations (10.0 months for compounded-only users vs. 7.8 months for brand-name-only users). The documented rate of 8.2% was substantially lower than the ~23% estimated by surveys, suggesting significant undocumented use outside coordinated primary care.","whyItMatters":"The rapid growth of compounded GLP-1 receptor agonists represents a major shift in how patients access peptide-based therapeutics. When patients use these medications without their primary care doctor's knowledge, it creates gaps in medication monitoring, drug interaction screening, and side effect management. This study quantifies that gap for the first time in a large dataset, highlighting a patient safety concern at the intersection of telehealth expansion, drug shortages, and consumer demand.","specificNumbers":"","methodology":"Retrospective cohort study using the American Family Cohort, a nationwide US database of electronic health records from primary care practices, covering January 1, 2021 to December 31, 2024. Brand-name prescriptions were identified from structured prescription data. Compounded formulation use was identified through clinical notes (unstructured text), reflecting what clinicians documented during visits.","limitations":"Compounded use was identified from clinical notes, which may undercount actual documentation if notes were incomplete or used inconsistent terminology. The database represents primary care practices only and does not capture care delivered by telehealth companies or aesthetic clinics directly. The 23% survey estimate used as a comparison may have its own biases. The study could not assess clinical outcomes or adverse events associated with compounded formulations."},{"rthcId":"RPEP-11355","title":"Heterogeneity in response to GLP-1 receptor agonists in type 2 diabetes in real-world clinical practice: insights from the DPV register - an IMI-SOPHIA study.","authors":"Heni, Martin; Frühwald, Lisa; Karges, Wolfram; Naudorf, Michael; Niemöller, Kathrin; Pagnia, Frank; Reindel, Jörg; Seufert, Jochen; Ufer, Gisa; Wagner, Christian; Holl, Reinhard W; Prinz, Nicole","year":2025,"journal":"Diabetologia, 68(8), 1666-1673","doi":"10.1007/s00125-025-06448-w","pmid":"40404820","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11356","title":"Comparative Efficacy of Tirzepatide, Liraglutide, and Semaglutide in Reduction of Risk of Major Adverse Cardiovascular Events in Patients with Obstructive Sleep Apnea and Type 2 Diabetes: Real-World Evidence.","authors":"Henney, Alex E; Riley, David R; Anson, Matthew; Heague, Megan; Hernadez, Gema; Alam, Uazman; Craig, Sonya; Cuthbertson, Daniel J","year":2025,"journal":"Annals of the American Thoracic Society, 22(7), 1042-1052","doi":"10.1513/AnnalsATS.202409-923OC","pmid":"40590655","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11357","title":"Obesity pharmacotherapy in older adults: a narrative review of evidence.","authors":"Henney, Alex E; Wilding, John P H; Alam, Uazman; Cuthbertson, Daniel J","year":2025,"journal":"International journal of obesity (2005), 49(3), 369-380","doi":"10.1038/s41366-024-01529-z","pmid":"38710803","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies several key findings regarding obesity pharmacotherapy in adults over 60:\n\n• Nine anti-obesity medications are currently approved, but clinical trial evidence in older adults is predominantly limited to incretin-based therapies: liraglutide, semaglutide, and tirzepatide\n• GLP-1 receptor agonists enhance weight loss and reduce cardiometabolic events in older populations\n• Critically, these drugs help maintain muscle mass during weight loss — addressing the primary safety concern in elderly obesity treatment\n• Recent evidence supports that intentional weight loss in older adults with overweight/obesity is effective and safe, reducing the historical reluctance to prescribe anti-obesity medications\n• Lifestyle interventions with emphasis on resistance training remain the foundation, with pharmacotherapy as an adjunct for refractory cases","whyItMatters":"The global elderly population is growing rapidly, and obesity rates in this group are rising in parallel. Untreated obesity in older adults accelerates functional decline, worsens cognition, and reduces quality of life on top of standard cardiometabolic risks. Establishing that GLP-1 peptide drugs are safe and effective in this population — without excessive muscle loss — could transform geriatric obesity management and improve millions of lives.","specificNumbers":"","methodology":"Narrative review of evidence on anti-obesity medications in adults over 60 years, drawing from clinical trial data, cardiometabolic outcome studies, and body composition analyses. The review focuses on incretin-based therapies as the primary evidence base for this age group.","limitations":"Narrative review methodology without systematic search or quality assessment. Most evidence for older adults comes from subgroup analyses of larger trials rather than dedicated elderly-focused studies. Long-term data on body composition changes and functional outcomes in older adults taking GLP-1 agonists are limited. The review acknowledges that future RCTs specifically designed for older adults are needed."},{"rthcId":"RPEP-11358","title":"Target Trial Emulations of GLP-1 and Dual GLP-1/GIP Agonists to Reduce Major Adverse Liver Outcomes in Type 2 Diabetes.","authors":"Henney, Alex E; Riley, David R; Anson, Matthew; Azmi, Shazli; Alam, Uazman; Cuthbertson, Daniel J","year":2025,"journal":"Liver international : official journal of the International Association for the Study of the Liver, 45(10), e70367","doi":"10.1111/liv.70367","pmid":"40980971","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11359","title":"Proinflammatory cytokine-induced alpha cell impairment in human islet microtissues is partially restored by dual incretin receptor agonism.","authors":"Henriksen, Kristine; Rufer, Chantal; Title, Alexandra C; Jawurek, Sayro; Hartmann, Bolette; Holst, Jens J; Knop, Filip K; Yesildag, Burcak; Størling, Joachim","year":2025,"journal":"Diabetologia, 68(7), 1492-1508","doi":"10.1007/s00125-025-06425-3","pmid":"40374968","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Long-term (6-day) exposure of human islet microtissues to proinflammatory cytokines (IL-1β, IFN-γ, TNF-α) created a type 1 diabetes-like phenotype with dose-dependent suppression of glucagon secretion at low glucose (2.8 mmol/L), reduced insulin and somatostatin secretion, decreased ATP content, increased cell death, and diminished key transcription factors (ARX, NKX6.1).\n\nCritically, while incretin treatment during cytokine exposure did not prevent damage, acute treatment with [D-Ala2]-GIP (with or without liraglutide) or tirzepatide after cytokine exposure partially restored low-glucose glucagon secretion. Alpha cells also retained partial responsiveness to L-arginine stimulation despite cytokine damage.","whyItMatters":"Hypoglycemia is the most immediate life-threatening complication in type 1 diabetes, and impaired glucagon counterregulation makes it worse. If incretin peptides can restore some glucagon response, they could provide a new strategy to reduce hypoglycemia risk — addressing an unmet need that affects nearly every person with type 1 diabetes.","specificNumbers":"","methodology":"Human pancreatic islet microtissues were exposed to proinflammatory cytokines for 1 or 6 days. Alpha cell function was measured using sequential glucose-dependent secretion assays. Additional assessments included ATP content, caspase-3/7 activity (cell death), chemokine secretion, and islet transcription factor and hormone content. Incretin receptor agonists were tested both during and after cytokine exposure.","limitations":"This is an in vitro study using isolated human islet microtissues, which don't fully replicate the complex in vivo environment of the pancreas. The cytokine model approximates but doesn't perfectly replicate type 1 diabetes pathology. Glucagon restoration was partial, not complete. No in vivo validation was performed, and the clinical relevance of the degree of restoration is uncertain."},{"rthcId":"RPEP-11360","title":"Novel active Trp- and Arg-rich antimicrobial peptides with high solubility and low red blood cell toxicity designed using machine learning tools.","authors":"Henson, Bridget A B; Li, Fucong; Álvarez-Huerta, José Ausencio; Wedamulla, Poornima G; Palacios, Arianna Valdes; Scott, Max R M; Lim, David Thiam En; Scott, W M Hayden; Villanueva, Monica T L; Ye, Emily; Straus, Suzana K","year":2025,"journal":"International journal of antimicrobial agents, 65(1), 107399","doi":"10.1016/j.ijantimicag.2024.107399","pmid":"39645171","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Machine learning tools screened two peptide libraries (8,192 and 512 sequences) rich in tryptophan and arginine residues. The top 220 peptides were synthesized and tested against MRSA (S. aureus USA 300).\n\nSix lead AMPs showed low IC₅₀ values against MRSA and were further characterized for: MICs against MRSA, E. faecalis, K. pneumoniae, E. coli, and P. aeruginosa; low red blood cell lysis (non-hemolytic); structural behavior in model membranes; and activity against cancer cell lines (HepG2, CHO, PC-3). The approach produced a large family of active, soluble, non-toxic antimicrobial peptides.","whyItMatters":"Traditional antimicrobial peptide discovery is slow and expensive. This study demonstrates that machine learning can rapidly screen thousands of peptide candidates in silico before synthesis, dramatically accelerating the identification of safe, effective antimicrobials for drug-resistant infections. The resulting framework can be applied to design future peptide libraries.","specificNumbers":"","methodology":"Two peptide libraries were designed with specific sequence templates enriched in tryptophan (Trp) and arginine (Arg). Machine learning tools ranked peptides for predicted antimicrobial activity and low hemolytic potential. The top 220 peptides (100 from each library plus 10 predicted to be hemolytic as controls) were SPOT synthesized and tested. Six leads underwent detailed characterization including MIC testing against five bacterial species, hemolysis assays, structural analysis by circular dichroism in membrane mimics, and cancer cell cytotoxicity.","limitations":"All testing was in vitro. In vivo efficacy, pharmacokinetics, and toxicity in animal models have not been assessed. Machine learning predictions, while useful for prioritization, are not perfect — the inclusion of predicted-hemolytic controls acknowledges this. Peptide stability in biological fluids and manufacturing scalability were not addressed."},{"rthcId":"RPEP-11361","title":"Advances in clinical neuro-oncology research on integrin PET imaging.","authors":"Henssen, Dylan; Herings, Siem; Sabri, Osama; Hesse, Swen; van der Kolk, Anja; Arens, Anne; Gotthardt, Martin","year":2025,"journal":"EJNMMI reports, 9(1), 33","doi":"10.1186/s41824-025-00270-8","pmid":"41016977","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 8 studies including 112 patients with primary and secondary brain tumors, RGD peptide PET tracers targeting αvβ3 integrin demonstrated several advantages:\n\n- Superior tumor-to-background ratios compared to standard [¹⁸F]FDG PET, enabling better detection of brain tumors against the naturally high glucose metabolism of brain tissue\n- Strong correlation between integrin expression on tumors and tracer uptake in studies with histopathological validation\n- Ability to predict treatment response: significant reductions in SUVmax (maximum standardized uptake value) after chemoradiotherapy and bevacizumab were linked to better patient prognosis\n- Zero adverse events related to the radiotracers across all studies","whyItMatters":"Standard FDG-PET scans struggle with brain tumors because healthy brain tissue also has high glucose uptake, making it hard to distinguish tumor from normal tissue. RGD peptide tracers target angiogenesis — the new blood vessel growth that feeds tumors — providing a signal that's much more specific to cancer. This could improve diagnosis, surgical planning, and monitoring of treatment effectiveness for one of the deadliest cancer types.","specificNumbers":"","methodology":"The researchers conducted a systematic literature search of PubMed, EMBASE, and Cochrane Library through November 2024. They included studies using RGD-based PET tracers in neuro-oncological imaging. Data on demographics, tumor types, imaging protocols, and outcomes were extracted. Study quality was assessed using QUADAS-2, the standard tool for evaluating diagnostic accuracy studies.","limitations":"Only 8 studies with 112 total patients were included — a small evidence base. Few studies included histopathological validation to confirm that tracer uptake truly reflected integrin expression. RGD PET tracers don't cross the blood-brain barrier, raising questions about whether some of the signal comes from nonspecific accumulation where the barrier is disrupted by the tumor rather than specific integrin binding. No randomized controlled trials were available."},{"rthcId":"RPEP-11362","title":"Acute mitochondrial reactive oxygen species emissions drive mitochondrial dysfunction after traumatic muscle injury in male mice.","authors":"Heo, Junwon; Miller, David L; Hoffman, Jessica R; Oberholtzer, Emma; Castelli, Katelyn M; Sparagna, Genevieve C; Fisher-Wellman, Kelsey H; Greising, Sarah M; Call, Jarrod A","year":2025,"journal":"American journal of physiology. Cell physiology, 329(1), C235-C250","doi":"10.1152/ajpcell.00407.2025","pmid":"40465482","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11363","title":"Glucagon-like peptide-1 receptor agonist use and perioperative outcomes after anterior cervical discectomy and fusion: a propensity-matched cohort study.","authors":"Heo, Kevin Y; Barchick, Stephen R; Sowa, Aubrie M; Chao, Myra; Rajan, Prashant V; Goh, Brian C; Yoon, Sangwook T","year":2025,"journal":"The spine journal : official journal of the North American Spine Society","doi":"10.1016/j.spinee.2025.12.019","pmid":"41482188","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 1,598 propensity-matched pairs (3,196 total patients), GLP-1 agonist users showed:\n\nNo increased aspiration risk: 0.81% vs 1.25% (P=0.39, not significant).\n\nReduced 90-day complications: DVT/PE 0.44% vs 0.94% (P=0.04); acute kidney injury 0.94% vs 1.69% (P=0.04); extended hospital stays (≥3 days) 15.96% vs 18.65% (P=0.04).\n\nNo differences at 1 year: DVT/PE 1.56% vs 2.00% (P=0.36); pseudoarthrosis/nonunion 2.82% vs 3.25% (P=0.50).\n\nImportantly, GLP-1 drugs did not impair bone fusion (pseudoarthrosis rates were equivalent), addressing another theoretical concern about these medications in spine surgery.","whyItMatters":"With millions of people now taking GLP-1 drugs, anesthesiologists and surgeons have been increasingly concerned about perioperative aspiration risk from delayed gastric emptying. Some guidelines recommend stopping GLP-1 drugs days before surgery or requiring additional fasting. This large study provides reassuring evidence that these drugs don't increase aspiration risk in anterior cervical surgery — and actually reduce other postoperative complications. For the estimated 500,000+ ACDF procedures performed annually, this has direct implications for perioperative medication management.","specificNumbers":"","methodology":"Retrospective propensity-matched cohort study using an administrative claims database. 20,941 patients with T2DM and/or obesity undergoing single or two-level primary ACDF between 2015-2022 were identified. GLP-1 agonist users (within 6 months before and after surgery) were matched 1:1 with non-users on age, sex, comorbidity index, insulin dependence, diabetic complications, other diabetes medications, morbid obesity, and smoking status. Multivariable logistic regressions examined 90-day and 1-year outcomes.","limitations":"Retrospective administrative database study — cannot establish causation. The database may not capture all instances of aspiration (mild cases may go undiagnosed). GLP-1 agonist adherence was assumed from prescription claims, not verified. Specific GLP-1 agents and doses were not differentiated. The timing of the last GLP-1 dose relative to surgery was unknown. The study period (2015-2022) includes years when GLP-1 use was less common, potentially limiting statistical power for rare events. Single surgical procedure type limits generalizability."},{"rthcId":"RPEP-11364","title":"Glucagon-Like Peptide-1 Receptor Agonist Use Is Not Associated With Increased Complications After Total Hip Arthroplasty in Patients Who Have Type 2 Diabetes.","authors":"Heo, Kevin Y; Goel, Rahul K; Woltemath, Alyssa; Fuqua, Andrew; Hrudka, Bryce T; Syed, Omar; Arellano, Emilio; Premkumar, Ajay; Wilson, Jacob M","year":2025,"journal":"The Journal of arthroplasty, 40(6), 1413-1418.e1","doi":"10.1016/j.arth.2024.10.099","pmid":"39486470","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11365","title":"Exenatide for diagnosing endogenous hyperinsulinemic hypoglycemia: a randomized placebo-controlled, double-blind, cross-over proof-of-principle study.","authors":"Hepprich, Matthias; Romberg, Christina; Mudry, Jonathan; Refardt, Julie; Wild, Damian; Antwi, Kwadwo; Christ, Emanuel","year":2025,"journal":"European journal of endocrinology, 193(2), 247-254","doi":"10.1093/ejendo/lvaf153","pmid":"40747712","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11366","title":"Comprehensive analysis of real-world data on liraglutide treatment in patients with obesity: a multicenter national study.","authors":"Hepşen, Sema; Haymana, Cem; Cavnar Helvacı, Burçak; Durantaş, Halil; Toros, Bora; Çakmak, Ramazan; Güven, Mehmet; Demirci, İbrahim; Keskin, Lezan; Kıyıcı, Sinem; Şahin Alak, Zehra Yağmur; Sargın, Mehmet; Tamer, Gonca; Balcı, Damla; Aydoğan, Berna İmge; Or Koca, Arzu; Aydemir, Mustafa; Tarkun, İlhan; Köksal, Pınar; Oğuz, Ayten; Demir Önal, Eda; Baldane, Süleyman; Kızılgül, Muhammed; Çakal, Erman; Çakır, Bekir; Polat, Şefika Burçak; Yetkin, İlhan; Bozkırlı, Emre; Karaahmetli, Gülsüm; Fakı, Sevgül; Yaghji, Narimana Imanova; Öge, Ayşin; Özbaş, Burak; Topsakal, Şenay; Fırat, Sevde Nur; Bostan, Hayri; Karagün, Barış; Bakıner, Okan Sefa; Kargılı Çarlıoğlu, Ayşe; Evren, Bahri; Uğur, Kader; Kılınç, Faruk; Batman, Adnan; Çakmak Demir, Selin; Yazıcı, Dilek; Deyneli, Oğuzhan; Arslan, Metin; Topaloğlu, Omercan; Kocatepe, Kübra; Karagözoğlu, Kemal; Tekin, Sakin; Bayraktaroğlu, Taner; Ertek Yalçın, Sibel; Kubat Üzüm, Ayşe; Kocamaz, Gökçem Yalın; Şahin, Mehtap; Aydın, Yusuf; Kutlu, Mustafa; Sabuncu, Tevfik; Cesur, Mustafa; Yumuk, Volkan Demirhan; Bayram, Fahri; Sönmez, Alper","year":2025,"journal":"European journal of medical research, 30(1), 956","doi":"10.1186/s40001-025-02836-5","pmid":"41074095","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11367","title":"Risk of suicidal ideation and suicidality among adults prescribed semaglutide for weight management: A population-based cohort study.","authors":"Her, Qoua L; Wang, Tiansheng; Stürmer, Til; Buse, John B; Jonsson Funk, Michele; Pate, Virginia; Webster-Clark, Michael","year":2025,"journal":"Diabetes, obesity & metabolism, 27(11), 6178-6187","doi":"10.1111/dom.70002","pmid":"40760781","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11368","title":"Actifensin Evolution in the Human Oral Cavity over the Past 100,000 Years.","authors":"Herbst, Rosa; Ibrahim, Anan; Hübner, Alexander; Knüpfer, Uwe; Regestein, Lars; Wiedemann, Christoph; Hellmich, Ute A; Warinner, Christina; Stallforth, Pierre","year":2025,"journal":"Journal of the American Chemical Society, 147(52), 48060-48071","doi":"10.1021/jacs.5c14335","pmid":"41407286","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Using a newly developed computational platform called AMPcombi, combined with metagenomics, structural modeling, and experimental validation, the researchers identified actifensins — a novel family of Actinomyces-derived defensin-like antimicrobial peptides — in dental biofilms spanning 100,000 years.\n\nActifensins were found across all time periods and in samples from humans, Neanderthals, and nonhuman primates, indicating remarkable evolutionary conservation. Phylogenetic and structural analyses revealed shared ancestry between ancient (paleo-) and modern actifensins, with evidence of positive selection driving adaptive diversification.\n\nCritically, experimental validation confirmed that both ancient and modern actifensins maintained antimicrobial activity, demonstrating that these peptides have been functional weapons in microbial competition for at least 100,000 years.","whyItMatters":"With antibiotic resistance threatening modern medicine, finding new antimicrobial compounds is urgent. This study reveals that ancient dental plaque preserves a 100,000-year evolutionary record of antimicrobial peptides that are still functional. This evolutionary perspective could identify peptides that have been 'battle-tested' by natural selection for millennia, potentially yielding more robust antibiotic candidates than lab-designed molecules. The approach also opens a new field: paleobiotechnology — mining ancient biomolecules for modern drug development.","specificNumbers":"","methodology":"The team combined multiple approaches: metagenomics analysis of ancient and modern dental calculus samples from humans, Neanderthals, and nonhuman primates; structural modeling to predict peptide structures; their newly developed AMPcombi platform to identify and compare antimicrobial peptides across samples; phylogenetic analysis to trace evolutionary relationships; and experimental antimicrobial assays to validate that identified peptides retained killing activity. The dental calculus samples spanned approximately 100,000 years.","limitations":"While actifensins demonstrated antimicrobial activity, the study does not report against which specific pathogens or at what concentrations. Ancient DNA analysis is subject to contamination and degradation challenges. The reconstructed ancient peptide sequences may not perfectly match the original molecules. The AMPcombi platform is newly developed and has not been independently validated by other groups. Translation from evolutionary discovery to therapeutic development remains a long path."},{"rthcId":"RPEP-11369","title":"The versatility of peptide hydrogels: From self-assembly to drug delivery applications.","authors":"Heremans, Julie; Ballet, Steven; Martin, Charlotte","year":2025,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 31(2), e3662","doi":"10.1002/psc.3662","pmid":"39561971","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Peptide-based hydrogels offer several advantages as controlled drug delivery systems: they self-assemble from simple peptide building blocks, are biocompatible, closely mimic the body's extracellular matrix, and can be fine-tuned in their physical properties.\n\nBeta-sheet forming peptide sequences are highlighted as particularly versatile building blocks for hydrogel formation. The review identifies an emerging trend toward affinity-based drug release systems, which use molecular recognition rather than simple diffusion to control when and how much drug is released — offering more precise therapeutic dosing compared to conventional hydrogel approaches.","whyItMatters":"As biologic drugs (peptides, proteins, antibodies) increasingly dominate the pharmaceutical pipeline, the need for better delivery systems grows. Many biologics are fragile and short-lived in the body. Peptide hydrogels could serve as injectable depots that protect these drugs and release them slowly, potentially reducing injection frequency and improving patient compliance. This is especially important for the growing class of peptide therapeutics.","specificNumbers":"","methodology":"This was a comprehensive narrative review of the published literature on peptide hydrogels for drug delivery. The authors examined different types of hydrogel systems, their self-assembly processes, the variety of peptide sequences used as building blocks, and the mechanisms by which drugs are released from these systems.","limitations":"This is a review article that summarizes the state of the field rather than reporting new experimental data. Most peptide hydrogel drug delivery systems discussed are in preclinical stages, and the review does not provide a systematic assessment of which systems have advanced to human trials. The translation from laboratory demonstrations to clinical use faces significant regulatory and manufacturing challenges that are not deeply explored."},{"rthcId":"RPEP-11370","title":"Anorexigenic and anxiogenic effects of the plasticiser DEHP (di-2-ethylhexyl phthalate) in goldfish: Involvement of PPAR signalling and feeding-related neuropeptides.","authors":"Herrera-Castillo, Lisbeth; Hernández-Villasevil, Claudia; Barany, André; Gómez-Boronat, Miguel; Isorna, Esther; de Pedro, Nuria","year":2025,"journal":"Comparative biochemistry and physiology. Part A, Molecular & integrative physiology, 306, 111878","doi":"10.1016/j.cbpa.2025.111878","pmid":"40350142","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11371","title":"Obtaining bioactive peptides by enhancing enzymatic hydrolysis of salmon by-product proteins through pulsed electric fields (PEF).","authors":"Herrera-Lavados, Carolina; Tabilo-Munizaga, Gipsy; Carvajal-Mena, Nailín; Jara-Quijada, Erick; Martínez-Oyanedel, José; Pérez-Won, Mario","year":2025,"journal":"Food research international (Ottawa, Ont.), 208, 116103","doi":"10.1016/j.foodres.2025.116103","pmid":"40263776","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Pulsed electric field (PEF) treatment at 15 and 20 kV/cm significantly improved enzymatic hydrolysis of salmon by-product proteins. When both the enzyme (flavourzyme) and the salmon protein were treated with PEF, the degree of hydrolysis increased from 9.6% to 16.6% and peptide yield increased from 10.6% to 18.7% — nearly doubling output.\n\nPEF treatment modified the protein's tertiary structure by decreasing surface hydrophobicity and intrinsic fluorescence, making the protein more accessible to enzymatic cleavage. The treatment also shifted the molecular weight distribution of the resulting peptides, increasing the proportion of smaller peptides (3 and 5 kDa). Optimal antioxidant and anti-ACE activities were achieved at 50 Hz and 15 kV/cm.","whyItMatters":"Millions of tons of fish processing by-products are discarded or underutilized annually. Converting this waste into valuable bioactive peptides addresses both sustainability and health — reducing environmental impact while producing compounds with antioxidant and blood pressure-lowering potential. PEF technology could make this process commercially viable by dramatically improving yields without using chemicals or extreme heat.","specificNumbers":"","methodology":"Salmon by-product proteins (SPI) were subjected to pulsed electric field treatment at various intensities (15 and 20 kV/cm) and frequencies, either treating the protein alone, the enzyme (flavourzyme) alone, or both together. Protein structural changes were characterized by surface hydrophobicity and intrinsic fluorescence measurements. The treated proteins were then enzymatically hydrolyzed, and the resulting peptides were analyzed for degree of hydrolysis, peptide yield, molecular weight distribution, antioxidant activity, and ACE inhibitory activity.","limitations":"This is a food technology study — all testing was performed in vitro. The antioxidant and ACE-inhibiting activities were measured in lab assays and may not translate directly to health benefits in humans. The bioavailability of these peptides after oral consumption was not studied. Only one enzyme (flavourzyme) and one protein source (salmon) were tested, so results may not generalize to other substrates."},{"rthcId":"RPEP-11372","title":"Set it and forget it: Engineered cells for drug delivery.","authors":"Herzog, Erik D; Pham, Christine T N; Guilak, Farshid","year":2025,"journal":"Cell systems, 16(12), 101484","doi":"10.1016/j.cels.2025.101484","pmid":"41412109","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11373","title":"Impact of Finerenone in Patients with Heart Failure and Reduced/Mildly Reduced Ejection Fraction, Diabetes Mellitus, and Chronic Kidney Disease.","authors":"Hida, Yuki; Imamura, Teruhiko; Kinugawa, Koichiro","year":2025,"journal":"Journal of clinical medicine, 14(22)","doi":"10.3390/jcm14227997","pmid":"41303034","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11374","title":"Effects of Tirzepatide on Skeletal Muscle Mass in Adults: A Systematic Review.","authors":"Hidalgo Ramos, Roberto A; Hong, Isaac; Ortiz, Marcelo; Secades, Daniela; Dufner Krieger, Sebastián; Ramos Stanziola, Linet","year":2025,"journal":"Cureus, 17(7), e89020","doi":"10.7759/cureus.89020","pmid":"40895971","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11375","title":"Semaglutide and Non-arteritic Anterior Ischemic Optic Neuropathy: A Systematic Review.","authors":"Hidalgo Ramos, Roberto A; Ortiz, Marcelo; Dufner Krieger, Sebastián; Secades, Daniela","year":2025,"journal":"Cureus, 17(8), e89656","doi":"10.7759/cureus.89656","pmid":"40926946","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11376","title":"Novel Use of Glucagon-Like Peptide-1 (GLP-1) and Dual Glucose-Dependent Insulinotropic Polypeptide (GIP)/GLP-1 Receptor Agonists in Maturity-Onset Diabetes of the Young (MODY).","authors":"Hilal, Abdalla; Afandi, Bachar; Almazrouei, Raya","year":2025,"journal":"Cureus, 17(10), e94882","doi":"10.7759/cureus.94882","pmid":"41262822","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"All six MODY patients (5 with HNF1A variants, 1 with PAX4/PDX1 variants) showed improvement on incretin-based therapy:\n- HbA1c reductions: 1.0-4.1 percentage points (from baseline range 7.3-10.6%)\n- Weight loss: 2.6-29 kg (from baseline BMI range 25.1-36.7 kg/m²)\n- Three of four insulin-treated patients discontinued insulin entirely\n- Two insulin-naïve patients maintained good glycemic control without needing insulin\n\nThis is notable because HNF1A-MODY patients are known to have enhanced sensitivity to incretins due to their genetic variant's effect on beta cell function.","whyItMatters":"MODY affects about 1-2% of all diabetes cases and is frequently misdiagnosed as type 1 or type 2 diabetes. Current treatments (sulfonylureas, insulin) have limitations including weight gain and hypoglycemia risk. This case series suggests GLP-1 receptor agonists could offer a better treatment option — improving blood sugar, promoting weight loss, and potentially eliminating the need for insulin injections.","specificNumbers":"","methodology":"Retrospective case series at Tawam Hospital (2019-2024) including patients with genetically confirmed MODY who received GLP-1 receptor agonist or dual GLP-1/GIP receptor agonist treatment for at least three months. Clinical data (HbA1c, BMI, insulin use) were extracted from medical records.","limitations":"Very small case series (n=6) without a control group. Retrospective design with potential selection bias (only patients who tolerated treatment are reported). Published in Cureus, which has variable peer review standards. The specific GLP-1RA and dual agonist used are not named in the abstract. Duration of follow-up varied. Results may not generalize to MODY caused by other gene variants."},{"rthcId":"RPEP-11377","title":"Cancer-Targeting Peptides Functionalized With Polyarginine Enables GRP78-Dependent Cell Uptake and siRNA Delivery Within the DU145 Prostate Cancer Cells.","authors":"Hilan, George; Daniel, Grace; Collak, Filiz; Sabatino, David; Willmore, William G","year":2025,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 31(3), e70007","doi":"10.1002/psc.70007","pmid":"39967318","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11378","title":"The role of dulaglutide in the treatment of alcohol use disorder: a case report.","authors":"Hill, Olivia; Hughes, Sarah; Singh, Aakanksha; Ang-Rabanes, Michael; Mogallapu, Raja","year":2025,"journal":"Frontiers in psychiatry, 16, 1420316","doi":"10.3389/fpsyt.2025.1420316","pmid":"40375882","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11379","title":"A new simple chronic heart failure prognostic index based on five general parameters.","authors":"Hipólito-Reis, Helena; Guimarães, Carolina; Elias, Catarina; Gouveia, Rita; Madureira, Sérgio; Reis, Catarina; Fonseca, Ana Margarida; Grijó, Carlos; Neves, Ana; Matos, Mariana; Rocha, Helena; Almeida, Jorge; Lourenço, Patrícia","year":2025,"journal":"International journal of cardiology, 423, 133002","doi":"10.1016/j.ijcard.2025.133002","pmid":"39864667","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The BASIC index formula — BNP × age² / (sodium × hemoglobin × eGFR) — was evaluated in 1,065 chronic heart failure outpatients with systolic dysfunction followed for a median of 47 months.\n\nKey results:\n- AUC: 0.73 (0.70-0.76) vs. 0.69 (0.66-0.72) for BNP alone (p < 0.001)\n- Optimal cut-off: 9.3 (sensitivity 71.4%, specificity 62.3%, PPV 66.5%, NPV 67.5%)\n- Patients with BASIC index > 9.3: adjusted hazard ratio for all-cause mortality = 2.70 (95% CI: 2.20-3.22)\n- During follow-up, 545 of 1,065 patients (51.2%) died\n- Median BASIC index: 11.7 (IQR: 3.5-33.7)","whyItMatters":"BNP is the most widely used peptide biomarker in heart failure, but alone it has limited prognostic accuracy. By combining BNP with four other readily available clinical values into a single number, the BASIC index provides a more complete picture of patient risk without requiring any additional testing. This could help clinicians identify high-risk patients who need more aggressive treatment, closer monitoring, or earlier referral for advanced therapies like heart transplant or mechanical support devices.","specificNumbers":"","methodology":"This was a retrospective cohort study of adult outpatients with chronic heart failure and systolic dysfunction followed at a single center from January 2012 to December 2020, with follow-up until January 2023. The BASIC index was calculated from five parameters measured at the index (baseline) visit. The primary endpoint was all-cause mortality. Receiver operating characteristic (ROC) curve analysis compared the index's predictive performance against BNP alone. Cox regression with multivariate adjustment for established prognostic predictors assessed independent prognostic value.","limitations":"This is a single-center retrospective study, which limits generalizability. The index has not been validated in an independent external cohort. The AUC improvement from 0.69 to 0.73, while statistically significant, is modest. The formula includes BNP (not NT-proBNP, a related but different assay), so applicability to centers using NT-proBNP needs evaluation. The study population was primarily elderly (mean age 71) and predominantly male (65.8%), which may not represent all heart failure populations. The index does not account for medications or ejection fraction."},{"rthcId":"RPEP-11380","title":"A Case of Slowly Progressive Type 1 Diabetes Mellitus (SPIDDM, Probable) Successfully Managed With Oral Semaglutide for Glycemic Control and Weight Management Accompanied by Changes in Eating Behavior.","authors":"Hirai, Taro; Kitada, Munehiro; Endo, Keita; Hayashi, Koichi; Suzuki, Toshihiko","year":2025,"journal":"Cureus, 17(11), e96335","doi":"10.7759/cureus.96335","pmid":"41367443","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A 23-year-old woman with slowly progressive type 1 diabetes (SPIDDM) who had poor blood sugar and weight control on insulin, dapagliflozin, and metformin achieved significant improvements after adding oral semaglutide. Her glycemic control improved enough to discontinue insulin entirely, she lost weight, and her eating behaviors improved. This case suggests GLP-1 RAs could be a valuable therapeutic option for SPIDDM — a form of autoimmune diabetes where some insulin production remains.","whyItMatters":"GLP-1 drugs are established for type 2 diabetes but their role in autoimmune (type 1) diabetes is unclear. SPIDDM/LADA is a challenging condition where patients retain some beta-cell function but gradually lose it. This case demonstrates that a GLP-1 peptide drug can successfully replace insulin therapy in certain autoimmune diabetes patients, potentially preserving remaining beta-cell function while improving both metabolic and behavioral outcomes.","specificNumbers":"n=1 · 23-year-old woman · SPIDDM since age 19 · oral semaglutide added · improved glycemic levels · weight improvement · insulin discontinued · eating behavior changes noted","methodology":"Single case report describing the clinical management of a 23-year-old Japanese woman with probable SPIDDM. Oral semaglutide was added to an existing regimen of insulin, dapagliflozin, and metformin. Clinical outcomes including glycemic control, weight, insulin requirements, and eating behavior were documented.","limitations":"As a single case report, findings cannot be generalized. The patient had 'probable' SPIDDM — the diagnosis was not definitively confirmed. Long-term beta-cell preservation was not assessed. Whether discontinuing insulin is safe long-term in autoimmune diabetes patients on GLP-1 therapy is unknown. Eating behavior changes were observationally reported rather than systematically measured."},{"rthcId":"RPEP-11381","title":"Low discontinuation rate of tirzepatide treatment in Japanese patients with diabetes mellitus; importance of traditional Japanese diet.","authors":"Hiraide, Takahiro; Suzuki, Yoshihiko; Yamamoto, Satoko; Yagihashi, Soroku; Sano, Motoaki","year":2025,"journal":"Journal of health, population, and nutrition, 44(1), 429","doi":"10.1186/s41043-025-01161-1","pmid":"41462404","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 219 Japanese diabetes patients treated with tirzepatide in real-world clinical practice, the discontinuation rate due to gastrointestinal adverse events was approximately 1.3% — dramatically lower than the 6-10% rates reported in Western clinical trials.\n\nDietary questionnaire data revealed a key behavioral pattern: patients reported reduced appetite specifically for high-fat and high-calorie foods, while maintaining their consumption of traditional Japanese low-carbohydrate foods such as fish and lean meat. This selective dietary shift toward the lower-fat traditional Japanese diet may have reduced the gastrointestinal burden that causes many Western patients to discontinue treatment.","whyItMatters":"GI side effects are the biggest barrier to GLP-1 and dual agonist therapy adherence. If dietary patterns significantly influence tolerability, this opens a practical intervention: dietary counseling tailored to minimize GI side effects could help more patients stay on these effective drugs. The Japanese experience suggests that a lower-fat, fish-rich diet may be the key to tolerating incretin-based therapies.","specificNumbers":"","methodology":"Real-world observational study of 219 Japanese patients with diabetes treated with tirzepatide. Discontinuation rates were tracked and compared to published Western trial data (6-10%). Dietary questionnaires assessed changes in food preferences and consumption patterns during tirzepatide treatment.","limitations":"This is a single-center observational study without a control group. The comparison to Western discontinuation rates (6-10%) is indirect, using published literature rather than a matched cohort. Genetic differences between Japanese and Western populations (body composition, metabolism, GI physiology) may also contribute and were not controlled for. Dietary questionnaires are subject to recall and social desirability bias. The sample size of 219 is modest."},{"rthcId":"RPEP-11382","title":"Mechanistic study of plasmid DNA delivery by Magainin 2-derived stapled peptides.","authors":"Hirano, Motoharu; Takechi-Haraya, Yuki; Abe, Yasuhiro; Misawa, Takashi; Shibata, Norihito; Sato, Yoji; Demizu, Yosuke","year":2025,"journal":"Bioorganic & medicinal chemistry, 123, 118176","doi":"10.1016/j.bmc.2025.118176","pmid":"40158418","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11383","title":"Glucagon-Like Peptide-1 Receptor Agonist Therapy Associated With Fewer Diagnoses of Carpal Tunnel Syndrome Within 2 Years of Treatment.","authors":"Hiredesai, Annika N; Holle, Alejandro M; Zhuang, Joyce; Howlett, Carina P; Lai, Cara H; Renfree, Kevin J; Noland, Shelley S","year":2025,"journal":"Hand (New York, N.Y.), 15589447251366676","doi":"10.1177/15589447251366676","pmid":"40899869","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11384","title":"Changes in food preferences after oral semaglutide administration in Japanese patients with type 2 diabetes: KAMOGAWA-DM cohort.","authors":"Hironaka, Junya; Ushigome, Emi; Kondo, Yuriko; Hashimoto, Yoshitaka; Osaka, Takafumi; Majima, Saori; Nakanishi, Naoko; Okada, Hiroshi; Senmaru, Takafumi; Hamaguchi, Masahide; Yamazaki, Masahiro; Fukui, Michiaki","year":2025,"journal":"Diabetes & vascular disease research, 22(1), 14791641251318309","doi":"10.1177/14791641251318309","pmid":"39878627","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11385","title":"Exploring factors predicting the effectiveness of oral semaglutide in Japanese individuals with type 2 diabetes switching from dipeptidyl peptidase 4 inhibitors: a pilot study.","authors":"Hirotsu, Takao; Taniguchi, Kanta; Nishimura, Rimei","year":2025,"journal":"Frontiers in clinical diabetes and healthcare, 6, 1520389","doi":"10.3389/fcdhc.2025.1520389","pmid":"40196376","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11386","title":"Impact of Glucagon-Like Peptide-1 Receptor Agonists on Retained Gastric Contents During Esophagogastroduodenoscopy: A Propensity Score-Matched Study.","authors":"Hisada, Hiroyuki; Tsuji, Yosuke; Kubota, Dai; Miura, Yuko; Mizutani, Hiroya; Ohki, Daisuke; Yakabi, Seiichi; Takeuchi, Chihiro; Kakushima, Naomi; Yamamichi, Nobutake; Fujishiro, Mitsuhiro","year":2025,"journal":"Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society, 37(12), 1340-1347","doi":"10.1111/den.70016","pmid":"40819843","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11387","title":"Drug-Induced Raynaud's Phenomenon and Underlying Mechanism: A Disproportionality Analysis From the World Health Organization Pharmacovigilance Database.","authors":"Hlavaty, Alex; Dari, Loubna; Cracowski, Jean-Luc; Roustit, Matthieu; Khouri, Charles","year":2025,"journal":"Arthritis & rheumatology (Hoboken, N.J.)","doi":"10.1002/art.43442","pmid":"41261736","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11388","title":"Glucagon-Like Peptide-1 Receptor Agonists and Peri-Procedural Aspiration Risk.","authors":"Ho, Cindy N; Ayers, Alessandra T; Kohn, Michael A; Umpierrez, Guillermo E; Klonoff, David C","year":2025,"journal":"Journal of the Endocrine Society, 9(9), bvaf088","doi":"10.1210/jendso/bvaf088","pmid":"40893948","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11389","title":"Association between glucagon-like peptide-1 receptor agonist therapy and respiratory illness in patients with type 2 diabetes: a retrospective observational cohort study.","authors":"Ho, Li-Ti; Fang, Yu-Wei; Hsu, Pei-Sung; Wang, Jing-Tong; Tsai, Ming-Hsien","year":2025,"journal":"Scientific reports, 15(1), 35625","doi":"10.1038/s41598-025-19657-5","pmid":"41083699","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11390","title":"Changes in Glucagon-Like Peptide-1 Receptor Agonist (GLP-1 RA) Exposures Following Recent Demand for Weight Management: A Retrospective Review of California Poison Control System Data.","authors":"Ho, Raymond Y; Regelman, Hsiaoting; Ma, Anita; Lee, Shu Yi; Sandhu, Saveena; Shapiro, Sarah; Lewis, Justin; Tsutaoka, Ben; Apollonio, Dorie E","year":2025,"journal":"The Journal of pharmacy technology : jPT : official publication of the Association of Pharmacy Technicians, 87551225251332212","doi":"10.1177/87551225251332212","pmid":"40371098","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11391","title":"The Impact of Metformin on BNP Levels: A Potential Cardioprotective Role in Type 2 Diabetes.","authors":"Hoca, Emre; Kalaycı, Nilsu; Ahbab, Süleyman; Engin, İsmail; Ataoğlu, Hayriye Esra","year":2025,"journal":"Journal of clinical medicine, 14(8)","doi":"10.3390/jcm14082733","pmid":"40283562","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11392","title":"2025 ADS/ANZCA/GESA/NACOS clinical practice recommendations on the peri-procedural use of GLP-1/GIP receptor agonists.","authors":"Hocking, Samantha L; Scott, David A; Remedios, Matthew L; Horowitz, Michael; Story, David A; Greenfield, Jerry R; Boussioutas, Alex; Devereaux, Benedict; Andrikopoulos, Sofianos; Shaw, Jonathan E; Olesnicky, Benjamin L","year":2025,"journal":"Anaesthesia and intensive care, 53(5), 300-306","doi":"10.1177/0310057X251355288","pmid":"40814081","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The multi-society expert panel recommends:\n1. All patients should be asked about GLP-1RA and GLP-1/GIPRA use before any procedure requiring sedation or anesthesia\n2. These medications should be continued in the peri-procedural period (not stopped)\n3. A 24-hour clear fluid diet followed by standard 6-hour fasting is recommended for all patients on these drugs\n4. If the liquid diet was not completed, gastric ultrasound or minimally sedated gastroscopy should assess stomach contents, and intravenous erythromycin may be used\n5. The absence of gastrointestinal symptoms cannot be relied upon for risk assessment\n6. No adequate cessation period can currently be recommended to ensure gastric emptying returns to baseline","whyItMatters":"With millions of patients now using GLP-1 receptor agonists for diabetes and obesity, the surgical safety implications are a growing clinical concern. These are among the first formal multi-society guidelines addressing this issue, providing practical recommendations for a situation that surgeons, anesthesiologists, and gastroenterologists encounter with increasing frequency.","specificNumbers":"","methodology":"An expert panel was assembled from four professional societies (Australian Diabetes Society, Australian and New Zealand College of Anaesthetists, Gastroenterological Society of Australia, and the National Australian Committee on Obesity Surgery) to review current evidence and develop consensus-based clinical practice recommendations.","limitations":"The guidelines are based on limited evidence, as there are few large studies specifically examining aspiration risk with GLP-1RAs during procedures. Recommendations are consensus-based rather than derived from randomized controlled trials. The guidelines are tailored for Australian and New Zealand practice and may not directly apply to other healthcare settings. The panel acknowledges they cannot yet recommend a safe cessation period."},{"rthcId":"RPEP-11393","title":"SAAP-148 Oligomerizes into a Hexamer Forming a Hydrophobic Inner Core.","authors":"Hodzic, Aden; Vejzovic, Djenana; Topciu, Altea; Kuhlmann, Kirill; Kumar, Raj; Mroginski, Maria Andrea; de Miguel, Alejandra; Hofmann, Pia; Zangger, Klaus; Weingarth, Markus; Cordfunke, Robert A; Drijfhout, Jan W; Nibbering, Peter; Belicka, Michal; Lohner, Karl; Malanovic, Nermina","year":2025,"journal":"Chembiochem : a European journal of chemical biology, 26(12), e202500112","doi":"10.1002/cbic.202500112","pmid":"40167522","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11394","title":"Neuropeptidergic systems in psychiatric disorders.","authors":"Hodzic, Sadat; Riedemann, Therese","year":2025,"journal":"Frontiers in endocrinology, 16, 1654292","doi":"10.3389/fendo.2025.1654292","pmid":"41641032","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11395","title":"Sequential use of OnabotulinumtoxinA and Erenumab in Chronic Migraine: Retrospective Real-World Report on Bidirectional Switching.","authors":"Hoehne, Carolin Luisa; Sahin, Aysenur; Overeem, Lucas Hendrik; Lange, Kristin Sophie; Fitzek, Mira Pauline; Angerhöfer, Cornelius; Reuter, Uwe; Raffaelli, Bianca","year":2025,"journal":"Neurology and therapy, 14(5), 2053-2061","doi":"10.1007/s40120-025-00803-0","pmid":"40751877","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11396","title":"Spinal Cord Stimulation - Device Revision After Weight Loss in a Patient on Chronic Semaglutide - A Case Report.","authors":"Hoffmann, Chelsey; Bendel, Markus A","year":2025,"journal":"International medical case reports journal, 18, 567-571","doi":"10.2147/IMCRJ.S513630","pmid":"40395634","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11397","title":"Relative Effectiveness and Safety of the GLP-1 (Glucagon-Like Peptide 1) Receptor Agonists, Semaglutide and Liraglutide in the Treatment of Obese Type 2 Diabetics: A Prospective Observational Cohort Study in Poland.","authors":"Hoffmann, Karolina; Michalak, Michał; Paczkowska, Anna","year":2025,"journal":"Diabetes, metabolic syndrome and obesity : targets and therapy, 18, 2723-2738","doi":"10.2147/DMSO.S531697","pmid":"40792001","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11398","title":"The efficacy and safety of dual GIP/GLP1 receptor agonists (tirzepatide) in diabetes and obesity: a systematic review and network meta-analysis.","authors":"Hoffmann, Karolina; Michalak, Michał; Rizzo, Manfredi; Maggio, Viviana; Paczkowska, Anna","year":2025,"journal":"Expert opinion on drug safety, 1-16","doi":"10.1080/14740338.2025.2586703","pmid":"41200927","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11399","title":"Oral Treatment of Obesity by GLP-1 and Its Analogs.","authors":"Holler, Natasa; Ruseska, Ivana; Schachner-Nedherer, Anna-Laurence; Zimmer, Andreas; Petschacher, Christina","year":2025,"journal":"Pharmaceutics, 17(12)","doi":"10.3390/pharmaceutics17121596","pmid":"41471111","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11400","title":"Appetite-related Gut Hormone Responses to Feeding Across the Life Course.","authors":"Holliday, Adrian; Horner, Katy; Johnson, Kelsie O; Dagbasi, Aygul; Crabtree, Daniel R","year":2025,"journal":"Journal of the Endocrine Society, 9(2), bvae223","doi":"10.1210/jendso/bvae223","pmid":"39777204","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11401","title":"RAMP1-dependent hormonal regulation of CGRP and its receptor in the trigeminal ganglion.","authors":"Holm, Anja; Edvinsson, Jacob C A; Krause, Diana N; Edvinsson, Lars","year":2025,"journal":"The journal of headache and pain, 26(1), 142","doi":"10.1186/s10194-025-02071-7","pmid":"40528180","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11402","title":"LEAP2 as a therapeutic target in obesity and cardiometabolic disorders.","authors":"Holm, Stephanie K; Johansen, Valdemar Brimnes Ingemann; Clemmensen, Christoffer","year":2025,"journal":"Reviews in endocrine & metabolic disorders","doi":"10.1007/s11154-025-10007-4","pmid":"41284160","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11403","title":"Sustained Weight Loss With Combined LEAP2 and Semaglutide Treatment in Mice.","authors":"Holm, Stephanie K; Johansen, Valdemar B I; Ranea-Robles, Pablo; Svendsen, Charlotte; Merrild, Christoffer; Rohlfs, Rebecca; Lo Conte, Mauro; Hogendorf, Wouter F J; Merkestein, Myrte; Zaykov, Alexander N; Fritzen, Andreas M; Mani, Bharath K; Clemmensen, Christoffer","year":2025,"journal":"Diabetes, 74(11), 2089-2100","doi":"10.2337/db24-1056","pmid":"40590720","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11404","title":"Complementary Yet Distinct Roles of GLP-1 Receptor Agonists and SGLT2 Inhibitors in Cardiovascular Risk Reduction.","authors":"Homoródi, Nóra; Varga, Éva; Szabó, Zoltán; Sztanek, Ferenc; Harangi, Mariann","year":2025,"journal":"Biomedicines, 13(11)","doi":"10.3390/biomedicines13112595","pmid":"41301689","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 receptor agonists reduce cardiovascular risk primarily through anti-atherosclerotic effects: they improve endothelial function, reduce inflammation, prevent blood clot formation, and stabilize arterial plaques. SGLT2 inhibitors achieve cardiovascular protection through different mechanisms: increasing sodium excretion, reducing plasma volume, promoting ketone body utilization in heart and kidney tissue, and lowering oxidative stress and uric acid levels.\n\nThe review concludes that these complementary mechanisms make the two drug classes suitable for different patient profiles, and their combination may offer additive cardiovascular benefits.","whyItMatters":"Heart disease is the leading cause of death in people with type 2 diabetes. Having two drug classes that protect the heart through entirely different pathways opens the door to personalized treatment — choosing GLP-1 drugs for patients with atherosclerosis risk versus SGLT2 inhibitors for those with heart failure or kidney concerns, or combining both for maximum protection. This review helps clinicians navigate these decisions with current evidence.","specificNumbers":"","methodology":"This is a comparative literature review synthesizing current evidence on the mechanisms of action, cardiovascular risk-reducing efficacy, and safety profiles of GLP-1 receptor agonists and SGLT2 inhibitors. The authors focused on identifying practical clinical factors that guide treatment selection between these two drug classes.","limitations":"As a narrative review, this paper synthesizes existing literature rather than presenting new clinical data. The comparison of mechanisms is based on current understanding, which continues to evolve. The review does not include meta-analytic quantification of effect sizes or head-to-head trial data comparing the two drug classes directly. Some proposed mechanisms (e.g., ketone body utilization for SGLT2 inhibitors) are still being validated."},{"rthcId":"RPEP-11405","title":"Risk of lower extremity complications with GLP-1 receptor agonists, SGLT2 inhibitors, and DPP-4 inhibitors in peripheral artery disease.","authors":"Hong, Alexander T; Lin, Forest; Luu, Ivan Y; Shin, Laura; Han, Sukgu M; Armstrong, David G; Tan, Tze-Woei","year":2025,"journal":"Diabetes research and clinical practice, 230, 112982","doi":"10.1016/j.diabres.2025.112982","pmid":"41177308","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11406","title":"Weight Loss Effects of Once-Weekly Semaglutide 2.4 mg in Adults with and Without Type 2 Diabetes: A Systematic Review and Meta-Analysis.","authors":"Hong, Boram; Kim, Haesoo; Lee, Daeun; Kim, Kisok","year":2025,"journal":"Pharmaceuticals (Basel, Switzerland), 18(7)","doi":"10.3390/ph18071058","pmid":"40732345","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11407","title":"Effects of Tirzepatide on Low-Density Lipoprotein Cholesterol Levels in Adults: A Systematic Review.","authors":"Hong, Isaac; Hidalgo Ramos, Roberto A; Dufner Krieger, Sebastián; Secades, Daniela; Ortiz, Marcelo; Moya Porras, Luis F; Piedra Pacheco, Ana L; Esquivel, Jose E","year":2025,"journal":"Cureus, 17(7), e88390","doi":"10.7759/cureus.88390","pmid":"40842811","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11408","title":"Advances in cell-penetrating peptide-based nose-to-brain drug delivery systems.","authors":"Hong, Shuai; Piao, Jinyou; Hu, Junsheng; Liu, Xinyu; Xu, Jing; Mao, Heying; Piao, Jingshu; Piao, Ming Guan","year":2025,"journal":"International journal of pharmaceutics, 678, 125598","doi":"10.1016/j.ijpharm.2025.125598","pmid":"40300721","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11409","title":"Innovative Strategy for Enhanced Delivery of Anti-Fibrotic miR-150 via PDGFR-Targeted Exosomes for Fibrosis Treatment.","authors":"Hong, Tae Ho; Park, Jung Hyun; Hong, Ha-Eun; Choi, Ho Joong; Kim, Ok-Hee; Kim, Say-June","year":2025,"journal":"Journal of Korean medical science, 40(44), e294","doi":"10.3346/jkms.2025.40.e294","pmid":"41250653","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11410","title":"Calcitonin Gene-Related Peptide Regulates Specific Interferon-Stimulating Genes to Inhibit Apoptosis of Corneal Epithelial Cells in Dry Eye Disease.","authors":"Hong, Xiaoping; Ding, Fadian; Zhang, Ling; Lv, Runhua; Chen, Jiaxin; Gao, YingYing","year":2025,"journal":"Investigative ophthalmology & visual science, 66(9), 65","doi":"10.1167/iovs.66.9.65","pmid":"40728362","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11411","title":"Poly-IC Alleviates Nitroglycerin-Induced Migraine by Inhibiting Neuroinflammation via TLR3/TRIF Signaling Pathway.","authors":"Hong, Ye; Ma, Mengmeng; Li, Changling; Zhang, Yang; Li, Yanbo; Chen, Ning; Fang, Jinghuan; He, Li","year":2025,"journal":"CNS neuroscience & therapeutics, 31(5), e70444","doi":"10.1111/cns.70444","pmid":"40406905","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11412","title":"LiaS-dependent activation of the MadR regulon enables cross-talk between Enterococcus faecalis cell envelope defense systems.","authors":"Hood, Kara S; Rizvi, Samie A; Hoppe-Elsholz, Guillermo A; Streling, Ana P; Panesso, Diana; Pratap, Shivendra; Shamoo, Yousif; Arias, Cesar A; Miller, William R","year":2025,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2025.06.19.660511","pmid":"40667240","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11413","title":"Modeling potential cost-effectiveness of tirzepatide versus lifestyle modification for patients with overweight and obesity.","authors":"Hoog, Meredith M; Kan, Hong; Deger, Kristen A; Sorensen, Sonja; Neff, Lisa M; Bae, Jay Patrick; Hankosky, Emily Ruth; Murphy, Madhumita; Mojdami, Donna; Houisse, Ivan; Harris, Mack S","year":2025,"journal":"Obesity (Silver Spring, Md.), 33(7), 1297-1308","doi":"10.1002/oby.24310","pmid":"40512029","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11414","title":"Real-World Effectiveness of Tirzepatide versus Semaglutide on HbA1c and Weight in Patients with Type 2 Diabetes.","authors":"Hoog, Meredith M; Vallarino, Carlos; Maldonado, Juan M; Grabner, Michael; Teng, Chia-Chen; Terrell, Kendra; Richard, Emma L","year":2025,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 16(11), 2237-2256","doi":"10.1007/s13300-025-01794-9","pmid":"41066072","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11415","title":"GLP-1RA-induced delays in gastrointestinal motility: Predicted effects on coadministered drug absorption by PBPK analysis.","authors":"Hooper, Levi; Liu, Shuhan; Pai, Manjunath P","year":2025,"journal":"Pharmacotherapy, 45(4), 211-219","doi":"10.1002/phar.70007","pmid":"39989027","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11416","title":"Multimodal Membrane Poration by Thanatin.","authors":"Hoose, Alex; Garcia-Ruiz, Javier; Blake, Corrin; Lally, Ciara C M; Briones, Andrea; Hoogenboom, Bart W; Lorenz, Christian D; Ryadnov, Maxim G","year":2025,"journal":"Langmuir : the ACS journal of surfaces and colloids, 41(6), 3757-3767","doi":"10.1021/acs.langmuir.4c03439","pmid":"39919312","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11417","title":"Pain in fibrous dysplasia: identifying nociceptive mechanisms in a preclinical model.","authors":"Hopkins, Chelsea; de Castro, Luis Fernandez; Benthin, Julie; Diaz-delCastillo, Marta; Manjappa, Pravallika; Boyce, Alison; Mendoza, Ruth Elena Martinez; Mora, Juan Antonio Vazquez; Lopez-Delgado, Giovanni Emmanuel; Gomez, Lizeth Yazmin Ponce; Mohamed, Khaled Elhady; Linley, John E; Collins, Michael T; Jimenez-Andrade, Juan Miguel; Heegaard, Anne-Marie","year":2025,"journal":"Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 40(7), 891-903","doi":"10.1093/jbmr/zjaf039","pmid":"40367355","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11418","title":"Racial differences in diuretic therapy, B-type natriuretic peptide values, and prognosis in acute heart failure.","authors":"Horiuchi, Yu; Matsue, Yuya; Wettersten, Nicholas; Oishi, Shogo; Akiyama, Eiichi; Suzuki, Satoshi; Yamamoto, Masayoshi; Kida, Keisuke; Okumura, Takahiro; Kitai, Takeshi; van Veldhuisen, Dirk J; Maisel, Alan; Murray, Patrick T; Minamino, Tohru","year":2025,"journal":"Journal of cardiology, 85(6), 486-493","doi":"10.1016/j.jjcc.2025.01.013","pmid":"39892868","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11419","title":"Time to weight plateau with tirzepatide treatment in the SURMOUNT-1 and SURMOUNT-4 clinical trials.","authors":"Horn, Deborah B; Kahan, Scott; Batterham, Rachel L; Cao, Dachuang; Lee, Clare J; Murphy, Madhumita; Gonsahn-Bollie, Sylvia; Chigutsa, Farai; Stefanski, Adam; Dunn, Julia P","year":2025,"journal":"Clinical obesity, 15(3), e12734","doi":"10.1111/cob.12734","pmid":"39800653","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11420","title":"Natriuretic peptides modulate monocyte-derived Langerhans cell differentiation and promote a migratory phenotype.","authors":"Horváth, Dorottya; Pénzes, Zsófia; Molnár, Petra; Rebenku, István; Vereb, György; Szántó, Magdolna; Muzsai, Szabolcs; Szegedi, Andrea; Dajnoki, Zsolt; Pázmándi, Kitti; Fekete, Tünde; Bácsi, Attila; Szöllősi, Attila Gábor","year":2025,"journal":"Frontiers in immunology, 16, 1593141","doi":"10.3389/fimmu.2025.1593141","pmid":"40552299","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11421","title":"Practical limitations of complex insulin therapies in type 2 diabetes: Focus on therapy simplification using fixed-ratio combinations of basal insulin and a glucagon-like peptide-1 receptor agonist.","authors":"Horváth, Luděk; Novodvorský, Peter; Haluzík, Martin","year":2025,"journal":"Diabetes, obesity & metabolism, 27 Suppl 7(Suppl 7), 42-54","doi":"10.1111/dom.16645","pmid":"40719033","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Current evidence shows that switching from complex insulin regimens to once-daily fixed-ratio combinations (FRCs) of basal insulin + GLP-1 RA provides equivalent glycemic control with additional benefits: reduced body weight, lower total daily insulin dose, fewer daily injections, and no increase (or a reduction) in hypoglycemia.\n\nTwo FRC products are currently available: iGlarLixi (insulin glargine + lixisenatide) and IDegLira (insulin degludec + liraglutide). The review provides a practice-oriented clinical algorithm for simplifying complex insulin regimens using these combinations.","whyItMatters":"Complex insulin regimens are a major burden for diabetes patients — multiple daily injections, blood sugar monitoring, weight gain, and fear of hypoglycemia reduce quality of life and adherence. Simplifying to a single daily injection that also promotes weight loss addresses several patient complaints at once, potentially improving both outcomes and quality of life.","specificNumbers":"","methodology":"This is a narrative review examining the current evidence supporting therapy simplification in type 2 diabetes. The authors reviewed clinical trial data for both available fixed-ratio combinations and synthesized the evidence into practical recommendations with a clinical algorithm for implementing the transition from complex insulin to FRC therapy.","limitations":"This is a narrative review, not a systematic review or meta-analysis. The clinical algorithm is based on existing evidence but represents expert opinion for practical implementation. Long-term outcomes beyond glycemic control (cardiovascular events, kidney outcomes) specifically for FRC therapy need more data. Cost and insurance coverage of FRCs may limit accessibility."},{"rthcId":"RPEP-11422","title":"Pancreatitis in Patients Receiving Tirzepatide (Mounjaro): A One-Year Audit in a UK District General Hospital.","authors":"Hossain, Asmita; Fahim, Muhammad; Abdalla, Moumn; Fozo, Khaldoun; Mon, Minthu; Kaholics, Botond; Veettil, Safana; Belgaumkar, Ajay; Carswell, Kirstin","year":2025,"journal":"Cureus, 17(11), e96974","doi":"10.7759/cureus.96974","pmid":"41409973","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11423","title":"In vitro assessment of an antimicrobial peptide against Acinetobacter baumannii persister cells.","authors":"Hosseini, Mandana; Hosseini, Farzaneh; Amirmozafari, Nour; Sepahy, Abbas Akhavan","year":2025,"journal":"Scientific reports, 16(1), 3226","doi":"10.1038/s41598-025-33137-w","pmid":"41454049","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A bioinformatically designed 20-amino acid antimicrobial peptide demonstrated potent activity against Acinetobacter baumannii with an MIC of 64 µg/mL. The peptide reduced persister cell populations by 75% within 24 hours — a critical finding since persister cells are responsible for chronic and recurring infections. It also inhibited biofilm formation and altered expression of the pmrB and lasI genes involved in antibiotic resistance and quorum sensing. Cytotoxicity to mammalian cells was moderate (8–17% reduction in cell viability).","whyItMatters":"Acinetobacter baumannii is classified by the WHO as a critical-priority pathogen due to extensive antibiotic resistance. Persister cells and biofilms make it even harder to treat. This peptide's ability to target persister cells specifically — which conventional antibiotics cannot do — represents a potentially breakthrough approach to combating one of medicine's most challenging infections.","specificNumbers":"20-amino acid peptide · MIC 64 µg/mL · 75% persister cell reduction in 24 h · 8–17% cytotoxicity to mammalian cells · biofilm reduction observed · pmrB and lasI gene expression altered","methodology":"Computational peptide design using bioinformatics tools followed by chemical synthesis of a 20-amino acid peptide. In vitro testing included minimum inhibitory concentration (MIC) assays, persister cell killing assays, biofilm inhibition assays, cytotoxicity testing on mammalian cells, and quantitative PCR for gene expression changes in pmrB (antibiotic resistance) and lasI (quorum sensing).","limitations":"This is an in vitro study only — the peptide has not been tested in animals or humans. The moderate cytotoxicity (8–17%) to mammalian cells is a concern that would need to be addressed for therapeutic development. The specific mechanism of action against persister cells was not fully elucidated. Only one bacterial species was tested."},{"rthcId":"RPEP-11424","title":"The dual impact of GLP-1 receptor agonists on metabolic and reproductive health in polycystic ovary syndrome: insights from human and animal trials.","authors":"Hoteit, Bassel H; Kotaich, Jana; Ftouni, Hadi; Hazime, Fatima; Safawi, Abdallah; Masri, Rim; Marwani, Mia","year":2025,"journal":"Therapeutic advances in endocrinology and metabolism, 16, 20420188251383064","doi":"10.1177/20420188251383064","pmid":"41069706","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11425","title":"Luteolin alleviates right ventricular hypertrophy in high altitude pulmonary hypertension rats by regulating PI3K/AKT/mTOR signalling pathway.","authors":"Hou, Bin; Su, Shanshan; Ji, Lei; Huayu, Meiduo; Yang, Na; Yang, Zhanting; Li, Zhanqiang; Lu, Dianxiang","year":2025,"journal":"European journal of pharmacology, 1003, 177898","doi":"10.1016/j.ejphar.2025.177898","pmid":"40609617","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11426","title":"Dynamic Visualization of Computer-Aided Peptide Design for Cancer Therapeutics.","authors":"Hou, Dan; Zhou, Haobin; Tang, Yuting; Liu, Ziyuan; Su, Lin; Guo, Junkai; Pathak, Janak Lal; Wu, Lihong","year":2025,"journal":"Drug design, development and therapy, 19, 1043-1065","doi":"10.2147/DDDT.S497126","pmid":"39974609","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11427","title":"Walnut Protein Peptide Nanoparticles with Protective Mineralization: Resveratrol Encapsulation, Intestinal-Targeted Delivery and Synergistic Antioxidant Activity.","authors":"Hou, Jingwen; Liu, Chao; Wen, Chaoting; Liu, Min; Xiang, Chunyan; Fang, Mengxue; Zhang, Liangxiao; Li, Peiwu","year":2025,"journal":"Foods (Basel, Switzerland), 14(24)","doi":"10.3390/foods14244310","pmid":"41465015","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11428","title":"Colocalisation of lanthipeptide production with genetic exchange and defence systems across prokaryote genomes.","authors":"Hourigan, David; Hill, Colin; Ross, R Paul","year":2025,"journal":"BMC genomics, 26(1), 1108","doi":"10.1186/s12864-025-12219-z","pmid":"41413859","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Analysis of 1,412 verified lanthipeptide biosynthetic gene clusters revealed a statistically significant co-localization with phage defense systems (including restriction-modification systems and CRISPR components) and bacterial competence genes within a 40 kb span. This pattern was observed across diverse species including Paenibacillus larvae, Corynebacterium matruchotii, Bacillus, Enterococcus, and Streptococcus.\n\nAnti-phage defense proteins were found near 1.2% of sampled regions, including the anti-restriction protein ArdA. The findings suggest an evolutionary model where antimicrobial peptide production, DNA defense, and horizontal gene transfer form an integrated system — bacteria kill competitors, absorb their DNA, and protect the newly acquired genetic material.","whyItMatters":"Understanding how bacteria organize their antimicrobial peptide genes could have practical implications for antibiotic discovery and engineering. If lanthipeptide production is part of a broader competitive strategy linked to gene transfer, it means these peptides play a more complex ecological role than simply killing other bacteria. This insight could help researchers better predict which bacteria produce useful antimicrobial compounds and how resistance might spread through bacterial communities.","specificNumbers":"","methodology":"The researchers performed a bioinformatic analysis of 1,412 verified class II lanthipeptide biosynthetic gene clusters from prokaryote genomes. They examined a 40 kb region surrounding each cluster for co-localization with other functional gene categories, including phage defense systems, restriction-modification systems, anti-CRISPR proteins, and bacterial competence genes. Statistical analyses assessed whether the observed co-localization exceeded what would be expected by chance.","limitations":"This is a purely bioinformatic/genomic analysis without experimental validation. Co-localization does not prove functional linkage — the genes near lanthipeptide clusters may not actually work together in practice. The 40 kb window is somewhat arbitrary, and the significance of proximity depends on species-specific genome organization. The study focused on class II lanthipeptides and may not generalize to all antimicrobial peptide classes."},{"rthcId":"RPEP-11429","title":"The use of GLP-1: receptor agonist medications for benign gynecology.","authors":"Howard, Megan D; Allen, Sarah E","year":2025,"journal":"Current opinion in obstetrics & gynecology, 37(4), 279-284","doi":"10.1097/GCO.0000000000001028","pmid":"40183300","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11430","title":"The Preventive Effects of GLP-1 Receptor Agonists and SGLT2 Inhibitors on Cancer Metastasis: A Network Meta-Analysis of 67 Randomized Controlled Trials.","authors":"Hsu, Chih-Wei; Zeng, Bing-Syuan; Liang, Chih-Sung; Zeng, Bing-Yan; Hung, Chao-Ming; Stubbs, Brendon; Chen, Yen-Wen; Lei, Wei-Te; Chen, Jiann-Jy; Chen, Po-Huang; Su, Kuan-Pin; Chen, Tien-Yu; Tseng, Ping-Tao","year":2025,"journal":"International journal of molecular sciences, 26(17)","doi":"10.3390/ijms26178202","pmid":"40943127","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11431","title":"NPFFR2 Deletion Improves Hypothalamic Insulin Sensitivity and Metabolic Outcomes in Mice With Diet-induced Obesity.","authors":"Hsu, Hsiang-Ting; Hsu, Chun-Chun; Tsai, Sze-Chi; Chen, Jin-Chung; Li, Hui-Yun; Lin, Ya-Tin","year":2025,"journal":"Endocrinology, 166(12)","doi":"10.1210/endocr/bqaf157","pmid":"41123466","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11432","title":"Glucagon-Like Peptide-1 Receptor Agonists in Gynecologic Surgery.","authors":"Hsu, Richard; Han, Esther; Swartz, Sarah; Pacis, Michelle","year":2025,"journal":"Obstetrics and gynecology, 146(6), 820-829","doi":"10.1097/AOG.0000000000006035","pmid":"40811820","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11433","title":"Fluid intake impact on heart failure: Systematic review and meta-analysis with trial sequential analysis.","authors":"Hsu, Suh-Meei; Lin, Yueh-Hung; Lin, Ying-Chun; Liu, Shu-Jung; Liu, Chih-Ju; Hung, Chung-Lieh; Wang, Tsae-Jyy","year":2025,"journal":"Journal of the Formosan Medical Association = Taiwan yi zhi, 124(7), 650-659","doi":"10.1016/j.jfma.2024.11.017","pmid":"39603913","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11434","title":"Association of tirzepatide use with risk of osteoporosis compared with other GLP-1 receptor agonists: A retrospective cohort study using the TriNetX database.","authors":"Hsu, Yung-Han; Liang, Yu-Cheng; Chan, Ka-Chon; Chou, Yu-Hsuan; Wu, Hung-Tsung; Ou, Horng-Yih","year":2025,"journal":"Diabetes research and clinical practice, 230, 112995","doi":"10.1016/j.diabres.2025.112995","pmid":"41218687","tags":[],"studyType":"retrospective-cohort","evidenceStrength":"moderate-high","keyFinding":"In a large real-world study of nearly 460,000 patients, tirzepatide was associated with a 44% higher risk of osteoporosis or fragility fractures compared to other GLP-1 receptor agonists (HR 1.44, 95% CI 1.22–1.69). Tirzepatide users were also 61% more likely to start osteoporosis therapy (HR 1.61, 95% CI 1.22–2.12).\n\nCompared to non-users, tirzepatide showed a 48% higher risk of osteoporosis/fracture (HR 1.48, 95% CI 1.26–1.75), while other GLP-1 agonists showed no significant increase (HR 1.07, 95% CI 1.00–1.15).\n\nThis suggests the bone risk may be specific to tirzepatide — possibly related to its dual GLP-1/GIP mechanism or the more rapid and greater weight loss it produces — rather than a class effect shared by all GLP-1 drugs.","whyItMatters":"Tirzepatide (Mounjaro/Zepbound) produces the most weight loss of any approved GLP-1-class drug. But rapid, significant weight loss can reduce bone density because bone remodeling doesn't keep pace with fat and muscle loss. This study raises an important safety signal: tirzepatide may carry higher osteoporosis and fracture risk than other GLP-1 drugs, which could be particularly concerning for older patients and postmenopausal women.","specificNumbers":"n=459,886 eligible · 66,329 matched per group · HR 1.44 vs other GLP-1 RAs · HR 1.48 vs nonusers · HR 1.61 for starting osteoporosis therapy · 14-month follow-up · June 2022–May 2024","methodology":"Retrospective cohort study using the TriNetX federated research network. Identified 459,886 patients with type 2 diabetes or obesity who started tirzepatide or other GLP-1 agonists between June 2022 and May 2024. Used 1:1 propensity score matching (66,329 per group) to balance baseline characteristics. Primary outcome was composite of new-onset osteoporosis or fragility fracture over 14 months.","limitations":"This is an observational study — it cannot prove tirzepatide directly causes bone loss, only that there's an association. Residual confounding is possible despite propensity score matching. Tirzepatide users may have higher BMI at baseline (since tirzepatide is often reserved for more severe obesity), which could influence fracture detection. The 14-month follow-up may be too short to capture the full fracture risk. The TriNetX database relies on diagnosis codes, which may have coding variability."},{"rthcId":"RPEP-11435","title":"Scymicrosin7-26, a Scylla paramamosain-derived novel antimicrobial peptide, exhibits efficacy against multidrug-resistant ESKAPE pathogens and anti-inflammatory activity.","authors":"Hu, Cong; Chen, Fangyi; Zhou, Ying; Yang, Ting; Wang, Kejian; Yang, Sheng; Chen, Xiangqi","year":2025,"journal":"Frontiers in microbiology, 16, 1732053","doi":"10.3389/fmicb.2025.1732053","pmid":"41480105","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11436","title":"RNA sequencing enables neoantigen discovery and vaccine validation in breast and lung cancer.","authors":"Hu, Hongye; Xiong, Yicheng; Lu, Danhong; Sun, Weihong; Su, Xiaoping; Mo, Danni; Chen, Lu; Wang, Guan; Wang, Jiayan; Zhang, Xiaohua; Lu, Mingdong; Huang, Guanli","year":2025,"journal":"Frontiers in immunology, 16, 1682312","doi":"10.3389/fimmu.2025.1682312","pmid":"41132668","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"An RNA-sequencing-only computational pipeline successfully identified neoantigens in mouse breast cancer (4T1), lung cancer (LLC), and one human breast cancer patient. In vitro, these neoantigen peptides triggered specific T-cell responses in BALB/c mice and the human patient. The neoantigen peptide group showed increased CD3+/CD137+ T cells (activated, tumor-specific T cells), with significant infiltration into tumor tissues. In vivo therapeutic evaluation demonstrated significant antitumor efficacy in mouse models.","whyItMatters":"Neoantigen-based cancer vaccines are one of the most promising approaches in personalized oncology, but their high cost and complexity limit widespread use. By eliminating the need for DNA sequencing, this RNA-only approach could cut costs and processing time significantly, making personalized cancer vaccines more accessible. If validated in larger human studies, this could accelerate the clinical adoption of neoantigen vaccines.","specificNumbers":"","methodology":"Researchers developed an in silico neoantigen prediction pipeline using only RNA sequencing data. Predicted neoantigen peptides were synthesized and tested in vitro using autologous bone marrow-derived dendritic cells (BMDCs) and peripheral blood mononuclear cells (PBMCs) to assess T-cell activation. In vivo efficacy was evaluated in mouse 4T1 breast cancer and LLC lung cancer models. T-cell infiltration was measured using CD3 and CD137 markers.","limitations":"Only one human breast cancer patient was included — the human validation is extremely preliminary. The mouse models (4T1, LLC) are well-established but don't capture the full heterogeneity of human tumors. The RNA-only pipeline may miss some neoantigens that are detectable only through DNA sequencing. No comparison with DNA/RNA combined approaches was presented to quantify the trade-off in sensitivity. Long-term tumor control and survival data were not reported."},{"rthcId":"RPEP-11437","title":"Study on the anticancer function and mechanism of cathelicidin-DM in liver cancer.","authors":"Hu, Huang; Tai, Jingjing; Zhang, Ruiyun; Zhang, Hong","year":2025,"journal":"Genomics, 117(3), 111049","doi":"10.1016/j.ygeno.2025.111049","pmid":"40288464","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11438","title":"A new type of ultrasonic water alleviates constipation with favorable safety.","authors":"Hu, Jiarong; Hu, Xinyi; Huang, Wenjie; Wang, Fen; Xia, Zhongqi; Zhu, Chenyang; Chow, Junwei; Yan, Shiwei; Li, Longzhou; Liu, Haiyang; Cui, Shufen; Ma, Guo","year":2025,"journal":"Frontiers in toxicology, 7, 1679872","doi":"10.3389/ftox.2025.1679872","pmid":"41357965","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11439","title":"Cinnamaldehyde attenuates diabetic cardiomyopathy by ameliorating energy metabolism disturbance and activating autophagy.","authors":"Hu, Ming-Qiao; Wei, Ke-Zhao; Wu, Shi-Yu; Zhang, Xu; Zhang, Xiao-Ting; Xu, Xu; Shen, Xu-Hua; Gao, Jian-Ping","year":2025,"journal":"Journal of cardiovascular pharmacology","doi":"10.1097/FJC.0000000000001694","pmid":"40153313","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11440","title":"Semaglutide Ameliorates Hepatocyte Steatosis in a Cell Co-Culture System by Downregulating the IRE1α-XBP1-C/EBPα Signaling Pathway in Macrophages.","authors":"Hu, Qin; Zhang, Li; Tao, YiTing; Xie, ShuangLin; Wang, AiYun; Luo, Caiying; Yang, RenHua; Shen, Zhiqiang; He, Bo; Fang, Yu; Chen, Peng","year":2025,"journal":"Pharmacology, 110(1), 26-35","doi":"10.1159/000540654","pmid":"39089233","tags":["glp-1-agonists","semaglutide"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Semaglutide reduced fat accumulation in liver cells by acting on nearby immune cells (macrophages) rather than directly on the liver cells themselves. In a co-culture system, semaglutide downregulated the IRE1α-XBP1-C/EBPα signaling pathway in macrophages, which reduced inflammation and indirectly improved hepatocyte health — reducing fat buildup, improving autophagy (cellular cleanup), and decreasing cell death. This suggests semaglutide's liver benefits may work partly through immune modulation rather than direct effects on liver cells.","whyItMatters":"Millions of people taking semaglutide for diabetes or weight loss are seeing improvements in fatty liver disease, but the mechanism hasn't been fully understood. This study reveals that semaglutide may work on the liver indirectly — by calming down inflammatory immune cells that worsen fat accumulation. Understanding this mechanism could lead to better-targeted therapies for NAFLD/MASH.","specificNumbers":"Semaglutide doses: 60 nM and 140 nM · 24-hour treatment · Oleic acid 0.4 mM + palmitic acid 0.2 mM for NAFLD modeling","methodology":"Researchers created a cell co-culture model of NAFLD by growing liver cells (AML12) together with macrophages (RAW264.7) in Transwell plates, inducing fat accumulation with oleic and palmitic acids. They treated with semaglutide at two concentrations and used pioglitazone (a diabetes drug) and toyocamycin (an XBP1 inhibitor) as controls. They measured fat content, autophagy, cell death, inflammation, and gene/protein expression in the signaling pathway.","limitations":"This is an in vitro cell culture study — not an animal or human study. The co-culture system using mouse cell lines doesn't capture the full complexity of human liver disease. The NAFLD model induced by fatty acids over 24 hours doesn't replicate the chronic, multifactorial nature of human NAFLD. Translation to in vivo and clinical settings requires further validation."},{"rthcId":"RPEP-11441","title":"Dual GIP and GLP-1 receptor agonist tirzepatide alleviates hepatic steatosis and modulates gut microbiota and bile acid metabolism in diabetic mice.","authors":"Hu, Weiting; Gong, Wenyu; Yang, Fan; Cheng, Rui; Zhang, Gerong; Gan, Lu; Zhu, Yikun; Qin, Weiwei; Gao, Ying; Li, Xing; Liu, Jing","year":2025,"journal":"International immunopharmacology, 147, 113937","doi":"10.1016/j.intimp.2024.113937","pmid":"39752752","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11442","title":"Effect of semaglutide with obesity or overweight individuals without diabetes: an Umbrella review of systematic reviews.","authors":"Hu, Xiaoye; Wang, Yongsheng; Yang, Kehu; Li, Xiuxia","year":2025,"journal":"Endocrine, 88(2), 387-397","doi":"10.1007/s12020-025-04179-x","pmid":"39955702","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11443","title":"Multistage Biobarrier-Adaptive Peptide Radiosensitizer with Low-Dose X-ray Augments Glioblastoma Radiotherapy via Destabilizing Lysosomal Homeostasis.","authors":"Hu, Xueyin; Cheng, Wei; Che, Jun; Chen, Yuanfang; Shang, Yue; Gao, Cong; Bi, Changfen; Fan, Saijun; Li, Shuqin; Liu, Luntao","year":2025,"journal":"ACS nano, 19(50), 42436-42454","doi":"10.1021/acsnano.5c15001","pmid":"41350241","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11444","title":"Mudskipper β-def2 exhibits potent broad-spectrum bactericidal activity via membrane-disrupting and DNA-targeting mechanisms.","authors":"Hu, Ya-Zhen; Tan, Ning-Xi; Cao, Jia-Feng; Chen, Jiong","year":2025,"journal":"Fish & shellfish immunology, 165, 110520","doi":"10.1016/j.fsi.2025.110520","pmid":"40571069","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Mudskipper β-def2 (muβ-def2, 43 amino acids, +4.5 net charge) demonstrated broad-spectrum bactericidal activity with MBCs ranging from <1 μM for S. aureus to 32 μM for L. monocytogenes. Rapid killing kinetics were observed (A. veronii eradication within 160 minutes). Activity persisted across 28°C-100°C and pH 5.5-9.0. The mechanism involves selective targeting of prokaryotic membrane phospholipids followed by downstream DNA interactions after membrane permeabilization. Pathogen-associated molecular patterns (PAMPs) competitively inhibited peptide activity.","whyItMatters":"With antibiotic resistance threatening global health, new antimicrobial agents — especially those with novel mechanisms — are urgently needed. This defensin's dual attack strategy (membrane disruption plus DNA targeting) makes it harder for bacteria to develop resistance than single-mechanism antibiotics. Its extreme stability across environmental conditions is also practically important for potential therapeutic or industrial applications where conventional antimicrobial peptides would degrade.","specificNumbers":"","methodology":"The researchers cloned, expressed, and characterized muβ-def2 from mudskipper fish. Structural analysis included phylogenetics and disulfide bond mapping (C1-C5, C2-C4, C3-C6). Antimicrobial activity was assessed by minimum bactericidal concentration assays, time-kill kinetics, and stability testing across temperature and pH ranges. Mechanism of action was investigated through membrane disruption assays and DNA interaction studies. PAMP competition experiments tested specificity.","limitations":"This is an in vitro characterization study without animal or human testing. MBC values against human pathogens may differ from the fish pathogens tested. The PAMP competition finding suggests potential issues with efficacy in complex biological environments. Cytotoxicity to mammalian cells was not reported. Manufacturing costs and delivery challenges for a 43-amino-acid peptide with 3 disulfide bonds would be significant."},{"rthcId":"RPEP-11445","title":"A highly active angiotensin I-converting enzyme inhibitory peptide KAKW designed based on the role of C-terminal residue, and its antihypertensive effects on spontaneously hypertensive rats.","authors":"Hu, Yangting; Xie, Dewei; Chen, Xujun; Li, Peng; Zhao, Li; Gao, Bei; Du, Lei; Xie, Jingli","year":2025,"journal":"European journal of medicinal chemistry, 290, 117564","doi":"10.1016/j.ejmech.2025.117564","pmid":"40153927","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11446","title":"Long- and Short-Term Cost-Effectiveness of Once-Weekly Semaglutide versus Dulaglutide for the Treatment of Type 2 Diabetes in China: A Hypothetical Modeling Exercise.","authors":"Hu, Ying; Zou, Huimin; Shen, Yang; Ni, Qi; Li, Yijun; Zhang, Hao; Chen, Xianwen; Ung, Carolina Oi Lam; Hu, Hao; Mu, Yiming","year":2025,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 16(5), 915-929","doi":"10.1007/s13300-025-01716-9","pmid":"40106226","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11447","title":"Long-Term Clinical and Economic Effects of Switching to Once-Weekly Semaglutide from Other GLP-1 RAs Among Patients with Type 2 Diabetes in China: A Modeling Projection Study.","authors":"Hu, Ying; Chen, Xianwen; Zou, Huimin; Zhang, Hao; Ni, Qi; Li, Yijun; Ung, Carolina Oi Lam; Hu, Hao; Mu, Yiming","year":2025,"journal":"Advances in therapy, 42(2), 904-917","doi":"10.1007/s12325-024-03082-7","pmid":"39680313","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11448","title":"Machine learning-driven prediction of readmission risk in heart failure patients with diabetes: synergistic assessment of inflammatory and metabolic biomarkers.","authors":"Hu, Yue; Zhang, Yunhong; Han, Ping; Pan, Yanqing; Liu, Juanjuan; Li, Yangni; Pan, Defeng; Ren, Jingjing","year":2025,"journal":"International journal of cardiology, 441, 133743","doi":"10.1016/j.ijcard.2025.133743","pmid":"40784376","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11449","title":"A peptide from Boletus griseus-Hypomyces chrysospermus protects against hypertension and associated cardiac and renal damage through modulating RAAS and intestinal microbiota.","authors":"Huan, Pengtao; Sun, Liping; Chen, Shupeng; Zhong, Yujie; Zhuang, Yongliang","year":2025,"journal":"Journal of food science, 90(1), e17617","doi":"10.1111/1750-3841.17617","pmid":"39786353","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"KF6 peptide administered at 10 mg/kg for 5 weeks to spontaneously hypertensive rats (SHRs) effectively lowered both diastolic blood pressure (DBP) and systolic blood pressure (SBP). The peptide decreased serum levels of ACE, angiotensinogen (AGT), aldosterone (ALD), and angiotensin II (ANG II).\n\nBeyond blood pressure reduction, KF6 ameliorated cardiac and renal injury by inhibiting fibrosis, inflammation, and oxidative stress. Mechanistically, it inhibited the ACE-ANG II-AT1 axis while activating the protective ACE2-Ang(1-7)-MAS1L pathway in both the kidney and heart. The peptide also improved intestinal microbiota composition, increasing beneficial Prevotella and Phascolarctobacterium while decreasing potentially harmful Alistipes, Clostridium_IV, Nosocomiicoccus, and Allobaculum.","whyItMatters":"Hypertension affects over a billion people worldwide and is a leading cause of heart disease, kidney failure, and stroke. Current ACE inhibitor drugs like Captopril are effective but come with side effects. Food-derived bioactive peptides represent a potentially safer alternative for blood pressure management. This study is notable because KF6 not only lowered blood pressure but also addressed organ damage and gut health, suggesting a multi-targeted therapeutic approach that synthetic drugs typically don't provide.","specificNumbers":"","methodology":"Researchers administered the KF6 peptide orally at 10 mg/kg body weight to spontaneously hypertensive rats (SHRs) for 5 weeks, comparing it to Captopril at the same dose as a positive control. They measured blood pressure throughout the study and analyzed serum biomarkers of the renin-angiotensin-aldosterone system (RAAS). Heart and kidney tissues were examined for signs of fibrosis, inflammation, and oxidative stress. Gut microbiota composition was assessed to evaluate intestinal effects.","limitations":"This study was conducted entirely in rats, so the results may not directly translate to humans. The spontaneously hypertensive rat model, while well-established, doesn't capture the full complexity of human hypertension. The study used only one dose level (10 mg/kg), so the optimal dose range is unknown. Long-term safety and efficacy beyond 5 weeks were not assessed. The gut microbiota changes were observational and the causal relationship between microbial shifts and blood pressure effects needs further investigation."},{"rthcId":"RPEP-11450","title":"Unmasking Euglycemic Diabetic Ketoacidosis: The Interplay of Pregnancy, Sepsis, and Glucagon-Like Peptide 1 Analog.","authors":"Huang, Alice; Lu, Jenny; Pancotto, Nicole; Sekhon, Gagandeep S; Gossen, Isabel M; Reyes, July M; Lazarescu, Roxana","year":2025,"journal":"Cureus, 17(1), e78193","doi":"10.7759/cureus.78193","pmid":"40026933","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11451","title":"Bronchopulmonary dysplasia induced by hyperoxia attenuated by A GLP-1 analog, Liraglutide, by regulating the ACE-2/Ang(1-7)/Mas receptor pathway.","authors":"Huang, Binglong; Luo, Han; Chen, Rou Yi; Li, Yeshan; Xiang, Min; Ao, Dang; Lin, Shaozhu; Liu, Ling","year":2025,"journal":"Pediatric research","doi":"10.1038/s41390-025-04293-6","pmid":"40897883","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Liraglutide significantly reduced levels of pro-inflammatory cytokines IL-1β, TNF-α, and IL-6 in bronchoalveolar lavage fluid and improved alveolar architecture in hyperoxia-exposed neonatal rats.\n\nAt the molecular level, liraglutide decreased mRNA and protein expression of ACE, AngII, and AT1R (P < 0.05) while increasing ACE-2 and Ang(1-7) expression (P < 0.05) at postnatal days 3, 7, and 14. When A779, a Mas receptor antagonist, was co-administered, liraglutide's protective effects were abolished, confirming the ACE-2/Ang(1-7)/Mas axis as the critical mechanism.","whyItMatters":"Bronchopulmonary dysplasia remains one of the most common and serious complications for premature infants, with limited treatment options. This study identifies a specific molecular mechanism through which a well-established GLP-1 drug could protect developing lungs, potentially opening a new therapeutic avenue for a vulnerable population.","specificNumbers":"","methodology":"Newborn Sprague-Dawley rats were divided into four groups: normal air control, hyperoxia-exposed (to induce BPD), hyperoxia plus liraglutide treatment, and hyperoxia plus liraglutide plus A779 (a blocker of the protective pathway). Lung tissues and fluid were collected at days 3, 7, and 14. Researchers used tissue staining to assess lung structure, ELISA to measure inflammatory markers, and RT-qPCR, Western blotting, and immunohistochemistry to measure molecular pathway activity.","limitations":"This was an animal study using neonatal rats, so results may not directly translate to human premature infants. The study did not test different doses of liraglutide or examine long-term outcomes beyond 14 days. Additionally, the BPD model was induced purely by hyperoxia, which may not fully capture the multifactorial causes of BPD in clinical settings."},{"rthcId":"RPEP-11452","title":"In vitro and in vivo osteogenesis of rat adipose-derived stem cells combined with calcium alginate gel scaffold induced by calcitonin gene-related peptide.","authors":"Huang, Changzhi; Liu, Xiaofeng; Lin, Liang; Zhang, Shimin; Xu, Nanyi; Wang, Xiaoyong; Lin, Jiuzao","year":2025,"journal":"Frontiers in cell and developmental biology, 13, 1669459","doi":"10.3389/fcell.2025.1669459","pmid":"41018261","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11453","title":"Association of GLP-1 receptor agonists with herpes risks in diabetes mellitus: a target trial emulation.","authors":"Huang, Chi-Hsien; Chiang, I-Hui; Lu, I-Cheng; Lai, Po-Hsuan; Liao, Pei-Lun; Huang, Jing-Yang; Hsieh, Ming-Ta; Lin, Chi-Wei; Liu, I-Ting; Wei, James Cheng-Chung","year":2025,"journal":"BMC medicine, 24(1)","doi":"10.1186/s12916-025-04606-w","pmid":"41469686","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11454","title":"Antimicrobial activity and immunomodulation of four novel cathelicidin genes isolated from the tiger frog Hoplobatrachus rugulosus.","authors":"Huang, Danni; Gao, Fulong; Huang, Yixin; Zheng, Ronghui; Fang, Chao; Huang, Wenshu; Wang, Kejian; Bo, Jun","year":2025,"journal":"Comparative biochemistry and physiology. Toxicology & pharmacology : CBP, 289, 110091","doi":"10.1016/j.cbpc.2024.110091","pmid":"39710086","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Four novel cathelicidin genes (cathelicidin-1 through cathelicidin-4) were cloned from tiger frog H. rugulosus, encoding peptides of 153, 188, 132, and 160 amino acids respectively. Sequence comparison revealed highly diverse structures among the four cathelicidins. Each showed distinct tissue-specific expression patterns in healthy frogs, with expression levels changing in tissue- and time-dependent manner when frogs were challenged with A. hydrophila bacteria over 72 hours.\n\nSynthetic cathelicidin-1 and cathelicidin-2 exhibited broad-spectrum in vitro antimicrobial activity through two mechanisms: excessive induction of reactive oxygen species (ROS) and direct disruption of microbial membrane structure. In vivo, intraperitoneal injection of cathelicidin proteins significantly increased marine medaka fish resistance to bacterial challenges, demonstrating cross-species antimicrobial protection.","whyItMatters":"Amphibian skin peptides are among nature's richest sources of antimicrobial compounds, evolved over hundreds of millions of years. The discovery of four structurally diverse cathelicidins in a single frog species reveals a sophisticated, multi-layered defense system that could inspire new antibiotic development. The dual killing mechanism (membrane disruption + ROS induction) makes bacterial resistance evolution particularly difficult, and the cross-species protective effect in fish demonstrates practical applications in aquaculture.","specificNumbers":"","methodology":"Full-length cDNA sequences of the four cathelicidins were cloned using RACE (rapid amplification of cDNA ends) technique. Phylogenetic analysis compared their structures to known cathelicidins. Real-time PCR measured tissue distribution in healthy frogs and time-course expression after A. hydrophila bacterial challenge over 72 hours. Synthetic peptides were tested for in vitro antimicrobial activity. Mechanisms were investigated through ROS measurement and membrane integrity assays. In vivo protection was assessed by injecting cathelicidin proteins into marine medaka fish before bacterial challenge.","limitations":"The study focused primarily on peptide discovery, characterization, and in vitro/fish in vivo testing. Human therapeutic potential was not directly assessed. The in vivo experiments used fish, not mammalian models. Potential toxicity to host cells was not comprehensively evaluated — an important consideration since ROS-inducing peptides could also damage host tissue. The specific MIC values and spectrum of bacterial targets are not detailed in the abstract. Production scale-up for practical aquaculture use was not addressed."},{"rthcId":"RPEP-11455","title":"Role of Neuronal Cholecystokinin Receptor: An Emerging Therapeutic Target for Ameliorating Neurological Diseases.","authors":"Huang, Feng-Wen; Bello, Stephen Temitayo","year":2025,"journal":"Molecular neurobiology, 63(1), 296","doi":"10.1007/s12035-025-05607-9","pmid":"41398125","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11456","title":"Breaking barriers in CRC immunotherapy: Cutting-edge advances in personalized peptide vaccine development.","authors":"Huang, Hairuo; Ren, Jianmin; Jiang, Deming; Hu, Shurong; Yu, Qiao; Tang, Bufu; Xu, Pingbo; Liu, Jingwen","year":2025,"journal":"Critical reviews in oncology/hematology, 216, 104967","doi":"10.1016/j.critrevonc.2025.104967","pmid":"40998030","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11457","title":"Glucagon-like peptide-1 receptor agonists and impaired gastric emptying: a pharmacovigilance analysis of the US Food and Drug Administration adverse event reporting system.","authors":"Huang, Haoquan; Hu, Chuwen; Liu, Fan; Ji, Fengtao; Fu, Yanni; Cao, Minghui","year":2025,"journal":"British journal of anaesthesia, 134(5), 1486-1496","doi":"10.1016/j.bja.2024.10.013","pmid":"39578156","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11458","title":"Management of Obesity in Menopausal Women: Implications for Metabolic Health and Minimally Invasive Surgery.","authors":"Huang, Hsuan-Wei; Ou, Yu-Che; Lin, Chia Yun; Lan, Kuo-Chung","year":2025,"journal":"Gynecology and minimally invasive therapy, 14(4), 289-296","doi":"10.4103/gmit.GMIT-D-25-00082","pmid":"41262087","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11459","title":"Pro-repair macrophages driven by CGRP rescue white matter integrity following intracerebral hemorrhage.","authors":"Huang, Huaping; Kuang, Yirui; Chen, Yang; Zhang, Yi; Zhou, Jiayin; Yu, Xian; Zheng, Yonghe; Cai, Lingxin; Hu, Wanglu; Gao, Liansheng; Wu, Haijian; Ling, Hui; Dong, Xiao; Zhou, Hang; Yu, Xiaobo; Peng, Yucong; Chen, Gao; Wang, Xiaoyu; Yan, Wei","year":2025,"journal":"Journal of neuroinflammation, 22(1), 161","doi":"10.1186/s12974-025-03483-7","pmid":"40544251","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11460","title":"Motilin stimulates food intake linked to gastric motility in Suncus murinus: Simultaneous recordings of food intake and gastric motility in the conscious state.","authors":"Huang, Jin; Watanabe, Ayumi; Kanaya, Moeko; Gomi, Ayano; Yokoyama, Haruka; Ishii, Hikari; Nakamura, Yusuke; Azuma, Morio; Konno, Norifumi; Kaiya, Hiroyuki; Sakai, Takafumi; Sakata, Ichiro","year":2025,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 122(28), e2424363122","doi":"10.1073/pnas.2424363122","pmid":"40627389","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Using house musk shrews (Suncus murinus) — one of the few small mammals that produce motilin — researchers demonstrated for the first time that the peptide hormone motilin directly stimulates food intake linked to gastric motility. Plasma motilin levels were elevated during phase III contractions of the migrating motor complex, and food intake was higher during these contractions. Intravenous motilin administration increased feeding during phase I (though less potently than ghrelin).\n\nCritically, motilin's feeding effect was completely abolished by vagotomy, proving the signal travels through the vagus nerve. Motilin also activated appetite-regulating neurons in the brainstem and hypothalamus, including neuropeptide Y neurons in the arcuate nucleus.","whyItMatters":"Motilin has long been known to trigger stomach contractions and hunger sensations, but direct evidence that it regulates food intake was lacking — partly because rats and mice lack functional motilin genes. This study fills that gap, establishing motilin as a genuine appetite-regulating peptide hormone and identifying the neural pathway (vagus nerve → brainstem → hypothalamus) through which it works. This positions motilin as a potential therapeutic target for appetite disorders, adding to the growing toolkit of gut peptides that could be harnessed for metabolic medicine.","specificNumbers":"Phase III vs Phase I contractions compared · Motilin feeding effect weaker than ghrelin · Vagotomy abolished motilin-induced feeding · c-Fos activation in area postrema, NTS, and arcuate nucleus · NPY neurons activated","methodology":"Researchers simultaneously monitored gastric contractions and food intake in conscious house musk shrews. Plasma motilin levels were measured during different phases of the migrating motor complex. Intravenous motilin and ghrelin were administered during phase I contractions to test feeding effects. Vagotomy was performed to test nerve dependency. Brain c-Fos immunohistochemistry identified activated neurons in appetite-regulating brain regions.","limitations":"The study used Suncus murinus (house musk shrew) rather than a more commonly studied animal, and results may not directly translate to humans. The relationship between motilin and food intake in humans requires clinical confirmation. The study focused on acute motilin administration rather than chronic effects. The comparison with ghrelin was limited and quantitative dose-response data were not fully detailed in the abstract."},{"rthcId":"RPEP-11461","title":"A retrospective observational study on case reports of adverse drug reactions (ADRs) to tirzepatide.","authors":"Huang, Mengmeng; Liu, Guangwei; Zhang, Chuanzhou; Wang, Ying; Liu, Shengfen; Zhao, Jun","year":2025,"journal":"Frontiers in pharmacology, 16, 1608657","doi":"10.3389/fphar.2025.1608657","pmid":"40667509","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11462","title":"Circulating CGRP as a diagnostic biomarker in female migraine patients: a single-center case-control study.","authors":"Huang, Qinyue; Li, Nanxi; Dou, Hanyu; Han, Haiyun; Suo, MeiJie; Wang, Yuhan; Jin, Jing; Wang, Xilong; Zhou, Xiaoxiao; Rong, Rong; Fan, Zhiming; Guan, Qiaochu; Xu, Yun; Zhang, Qingxiu","year":2025,"journal":"The journal of headache and pain, 26(1), 222","doi":"10.1186/s10194-025-02166-1","pmid":"41107707","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11463","title":"The safety and efficacy of liraglutide combined with metformin in clinical treatment of polycystic ovary syndrome patients: a meta-analysis.","authors":"Huang, Rongmei; He, Yinan","year":2025,"journal":"BMC women's health, 25(1), 282","doi":"10.1186/s12905-025-03787-z","pmid":"40481408","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11464","title":"Construction of human pluripotent stem cell-derived testicular organoids and their use as humanized testis models for evaluating the effects of semaglutide.","authors":"Huang, Rufei; Xia, Huan; Meng, Tao; Fan, Yufei; Tang, Xun; Li, Yifang; Zhang, Tiantian; Deng, Jingxian; Yao, Bing; Huang, Yadong; Yang, Yan","year":2025,"journal":"Theranostics, 15(6), 2597-2623","doi":"10.7150/thno.104523","pmid":"39990223","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11465","title":"Short-term predictive value of sST2 in patients with STEMI following primary PCI: a prospective observational study.","authors":"Huang, Shan; Yu, Lu-Jiao; Sun, Guang-Feng; Zhang, Zi-Xin","year":2025,"journal":"BMC cardiovascular disorders, 25(1), 21","doi":"10.1186/s12872-025-04488-z","pmid":"39819309","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11466","title":"Multifunctional D-Type Peptide Dendrimer-Based Nanocarriers Enabling Inherent Autophagy Modulation and Lysosomal Escape for Breast Tumor Therapy.","authors":"Huang, Shaoteng; Cai, Xiaofeng; Zhang, Mingbo; Yao, Wenjie; Fang, Quanhui; Dong, Yiwen; Zhang, Yong; Chen, Yang; Zhuang, Junyang; Li, Ning","year":2025,"journal":"Biomacromolecules, 26(9), 6340-6354","doi":"10.1021/acs.biomac.5c01439","pmid":"40866363","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"D-type peptide dendrimers demonstrated superior autophagy-inducing potential compared to both L-type dendrimers and free chemotherapeutics, as confirmed by TEM and Western blot. The histidine-modified dendrimer terminals enabled efficient lysosomal escape after cell internalization, leading to rapid drug release. The dendrimers synergized with encapsulated chemotherapeutic agents to enhance autophagy-mediated cancer cell death, serving both as carriers and active therapeutic components.","whyItMatters":"Chemotherapy's two biggest problems are toxic side effects (from drugs reaching healthy cells) and treatment resistance (cancer cells defending themselves through low-level autophagy). This peptide dendrimer system addresses both simultaneously: it delivers drugs precisely to cancer cells while actively turning their defense mechanism — autophagy — against them at lethal levels. The use of D-type (mirror-image) peptides also makes the carrier more resistant to degradation by the body's enzymes.","specificNumbers":"","methodology":"Multifunctional D-type peptide dendrimers were designed and synthesized with histidine-modified terminals for lysosomal escape. The nanocarriers were characterized and loaded with chemotherapy drugs. Autophagy induction was assessed using transmission electron microscopy (TEM) and Western blot, comparing D-type dendrimers versus L-type dendrimers and free drug. Cancer cell internalization, lysosomal escape, drug release, and therapeutic efficacy were evaluated in breast cancer cell models.","limitations":"This is an in vitro cell line study without animal model validation. The comparison between D-type and L-type dendrimers, while promising, needs confirmation in vivo where biodistribution, immune response, and toxicity profiles may differ. The specific chemotherapeutic drug loaded was not named in the abstract. Long-term stability and manufacturing scalability of the peptide dendrimers were not addressed."},{"rthcId":"RPEP-11467","title":"Disulfide-Rich Self-Assembling Peptides Based on Aromatic Amino Acid.","authors":"Huang, Wenjing; Dong, Huilei; Yan, Qipeng; Deng, Tingfen; Li, Xiaoxu; Zhao, Zhe; Li, Zenghui; Wang, Mingshui; Zhang, Chunhui; Kong, Bo; Shi, Junfeng; Yuan, Dan","year":2025,"journal":"Small (Weinheim an der Bergstrasse, Germany), 21(1), e2407464","doi":"10.1002/smll.202407464","pmid":"39491516","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11468","title":"Compound nucleotides as feed attractants improve the survival, growth, digestion, antioxidant capacity, and immunity of large yellow croaker (Larimichthys crocea) larvae.","authors":"Huang, Wenxing; Xu, Wenxuan; Yao, Chuanwei; Liu, Yongtao; Xu, Ning; Yin, Zhaoyang; Miao, Youqing; Mai, Kangsen; Ai, Qinghui","year":2025,"journal":"Fish & shellfish immunology, 165, 110435","doi":"10.1016/j.fsi.2025.110435","pmid":"40398504","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11469","title":"LAPTM5 exacerbates STING-mediated inflammation induced by LL-37 through stabilizing STING in rosacea.","authors":"Huang, Wenyue; He, Hailun; Wu, Haien; Wang, Yichong; Wang, Jingyu; Sun, Yan; Wang, Hexiao; Yao, Shulan; Zhu, Linlin; Jiang, Yi; Cai, Xinze; Wu, Yan","year":2025,"journal":"Communications biology, 8(1), 1470","doi":"10.1038/s42003-025-08861-8","pmid":"41087666","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11470","title":"\"Why you should (not) use semaglutide?\": A critical discourse analysis on health professionals' videos of semaglutide for weight loss on Douyin.","authors":"Huang, Xiang","year":2025,"journal":"Social science & medicine (1982), 382, 118339","doi":"10.1016/j.socscimed.2025.118339","pmid":"40582256","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11471","title":"A narrative review of autophagy in migraine.","authors":"Huang, Yanan; Li, Hongyan; Yu, Qijun; Pan, Yonghui","year":2025,"journal":"Frontiers in neuroscience, 19, 1500189","doi":"10.3389/fnins.2025.1500189","pmid":"40027467","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11472","title":"Designing Programmable Peptide Nucleic Acid-based Nanovaccines for Anticancer Immune Activation.","authors":"Huang, Yanyu; Huang, Cuiqing; Pandita, Sakshi; Ieong, Chon Man; Wang, Yongheng; Wang, David; Chen, Jifeng; Jauregui-Matos, Victorio; Beelen, Alessandra Maria Arabelle; Shiau, Ya-Ping; Tang, Shiqi; Zhao, Junwei; Zong, Qiufang; Tang, Menghuan; Cong, Zhaoqing; Li, Yuanpei; Beal, Peter A; David, Sheila S; Wang, Aijun; Wang, Duo; Xiao, Zeyu; Lam, Kit S","year":2025,"journal":"Small (Weinheim an der Bergstrasse, Germany), 21(51), e05605","doi":"10.1002/smll.202505605","pmid":"41201142","tags":[],"studyType":"animal","evidenceStrength":"preliminary","keyFinding":"Researchers built a programmable nanovaccine platform using peptide nucleic acid (PNA) scaffolds that can be loaded in a single step with three components: a cancer-targeting peptide antigen (SIINFEKL from ovalbumin), an immune-boosting adjuvant (CpG), and a dual-targeting ligand (LLP2A) that homes to both immune cells and melanoma cells via α4β1 integrin.\n\nIn mice with melanoma, this nanovaccine activated dendritic cells for antigen presentation, triggered strong CD8+ T cell and natural killer cell responses, caused significant tumor regression, and prolonged survival. The modular design allows swapping in different antigens and targeting ligands for personalized cancer vaccines.","whyItMatters":"Cancer vaccines struggle with two problems: getting antigens and immune boosters to the right cells, and doing so without causing runaway inflammation. This PNA-based platform solves both by precisely targeting immune and tumor cells while assembling all components in a simple one-pot reaction. The modular, programmable nature means it could be rapidly customized for individual patients' tumor antigens — a key step toward practical personalized cancer immunotherapy.","specificNumbers":"11-mer PNA scaffold · 3 components loaded in one pot · Targets α4β1 integrin on immune + melanoma cells · Strong CD8+ T cell + NK cell responses · Significant tumor regression + prolonged survival in B16-OVA melanoma mice","methodology":"Designed peptide nucleic acid nanovaccines using an 11-mer PNA scaffold loaded with antigenic peptide, CpG adjuvant, and LLP2A targeting ligand. Characterized structure using super-resolution fluorescence imaging and circular dichroism spectroscopy. Tested immune activation (dendritic cell antigen presentation, CD8+ T cells, NK cells) and therapeutic efficacy in C57BL/6 mice bearing B16-OVA syngeneic melanoma tumors.","limitations":"Preclinical mouse model only — the B16-OVA melanoma model uses a foreign antigen (ovalbumin) which is easier for the immune system to recognize than real human tumor antigens. Translation to human cancers with more complex, self-derived neoantigens will be more challenging. Manufacturing scalability and cost of PNA-based platforms for clinical use are not addressed. Long-term safety data is lacking."},{"rthcId":"RPEP-11473","title":"Acute Effects of Oral Microbial Protease Co-ingestion with Whey Protein on Postprandial Plasma Amino Acid Concentrations, Appetite, and Satiety in Healthy Adults: A Randomized, Double-Blind, Placebo-Controlled, Crossover Clinical Trial.","authors":"Huang, Yijia; Bell, Zachary W; Alhamwi, Alyasamin; Sauvageau, Benjamin; Malenda, Divine; Gardy, Silar; Krauth-Ibarz, Thalia; Hannaian, Sarkis J; Correa, José A; Gritsas, Ari; Garvey, Sean M; Tinker, Kelly M; Abou Sawan, Sidney; Morais, José A; Churchward-Venne, Tyler A","year":2025,"journal":"The Journal of nutrition, 155(10), 3356-3373","doi":"10.1016/j.tjnut.2025.07.006","pmid":"40675336","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11474","title":"Comparative ocular outcomes of tirzepatide versus other anti-obesity medications in people with obesity.","authors":"Huang, Yu-Nan; Chen, Jo-Ching; Li, Pin-Hung; Hsu, Min-Yen; Cheng, Chun-Wen; Meyerowitz-Katz, Gideon; Su, Pen-Hua","year":2025,"journal":"Communications medicine, 5(1), 329","doi":"10.1038/s43856-025-01066-4","pmid":"40750822","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11475","title":"The Effects of Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists on Polycystic Ovarian Syndrome: A Scoping Review.","authors":"Hudanich, Mia; Smith, Shannon N; Marino, Amanda; Riskin, Suzanne I","year":2025,"journal":"Cureus, 17(9), e93104","doi":"10.7759/cureus.93104","pmid":"41141001","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11476","title":"Cost-Effectiveness of Obesity Treatments: Glucagon-Like Peptide-1 Receptor Agonists, Endoscopic Sleeve Gastroplasty, and Metabolic/Bariatric Surgery.","authors":"Huh, Yeon-Ju","year":2025,"journal":"Journal of metabolic and bariatric surgery, 14(2), 97-105","doi":"10.17476/jmbs.2025.14.2.97","pmid":"40917206","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review's comparative findings across obesity treatment modalities:\n\n- **GLP-1 receptor agonists**: ~15-20% weight reduction, but high ongoing costs place ICERs above conventional willingness-to-pay benchmarks, meaning they rarely meet standard cost-effectiveness thresholds at current pricing.\n- **Endoscopic sleeve gastroplasty (ESG)**: ~15% weight loss with favorable cost-effectiveness, particularly in class I obesity (BMI 30-35).\n- **Metabolic/bariatric surgery (MBS)**: 25-30% weight loss with improvements in survival and quality of life. Consistently rated highly cost-effective and sometimes cost-saving, especially for class II (BMI 35-40) and class III (BMI 40+) obesity.\n\nESG is generally more economically favorable than GLP-1 RAs in class I obesity, while MBS dominates for more severe obesity. Head-to-head ESG vs. MBS comparisons remain limited.","whyItMatters":"GLP-1 drugs are generating billions in revenue as obesity treatments, but this review raises a critical question: are they good value? With annual costs often exceeding $10,000-15,000 per patient indefinitely, they fail standard cost-effectiveness tests. This has major implications for insurance coverage decisions, healthcare budgets, and individual patients weighing their options — particularly as cheaper alternatives like surgery offer more weight loss at lower long-term cost.","specificNumbers":"","methodology":"Narrative review synthesizing evidence from published clinical studies and health economic analyses. The authors compared incremental cost-effectiveness ratios (ICERs) and cost per quality-adjusted life year (QALY) across obesity severity classes. Special attention was given to implications for Korea's healthcare system.","limitations":"This is a narrative review, not a systematic analysis or meta-analysis. Cost-effectiveness data varies significantly by country, healthcare system, and pricing structure — the Korean context focus limits generalizability. GLP-1 drug prices are evolving rapidly with new entrants and competition. The review does not account for patient preferences, quality of life during treatment, or the psychological impact of surgery versus medication. Long-term data beyond 5 years is limited for newer GLP-1 agents."},{"rthcId":"RPEP-11477","title":"Glucagon-like peptide-1 receptor agonists and obesity paradox in heart failure with preserved ejection fraction: a systematic review.","authors":"Hullon, Darshan; Janiec, Karolina; Florova, Violetta; Trach, Adam; Volkova, Yelizaveta; Mnevets, Ruslan","year":2025,"journal":"Cardiovascular endocrinology & metabolism, 14(4), e00344","doi":"10.1097/XCE.0000000000000344","pmid":"40978810","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11478","title":"The role of glucagon-like peptide-1 receptor (GLP-1R) agonists in enhancing endothelial function: a potential avenue for improving heart failure with preserved ejection fraction (HFpEF).","authors":"Hullon, Darshan; Subeh, Ghasaq K; Volkova, Yelizaveta; Janiec, Karolina; Trach, Adam; Mnevets, Ruslan","year":2025,"journal":"Cardiovascular diabetology, 24(1), 70","doi":"10.1186/s12933-025-02607-w","pmid":"39920668","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11479","title":"Effects of glucagon-like peptide-1 on systemic hemodynamics, kidney function, and intrarenal oxygenation in sheep with sepsis-associated acute kidney injury.","authors":"Hulst, Abraham H; Ow, Connie P C; May, Clive N; Hood, Sally G; Plummer, Mark P; Hermanides, Jeroen; van Raalte, Daniël H; Deane, Adam M; Bellomo, Rinaldo; Lankadeva, Yugeesh R","year":2025,"journal":"Scientific reports, 16(1), 3250","doi":"10.1038/s41598-025-33109-0","pmid":"41444417","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11480","title":"Dual Glucagon-Like Peptide-1 (GLP-1) and Glucose-Dependent Insulinotropic Polypeptide (GIP) Receptor Agonist-Associated Thyroiditis: A Case Report of Thyroid Dysfunction Following Tirzepatide Use.","authors":"Humaida, Sara; Manzalji, Kamar; Seyam, Naheel; Al-Masalmani, Lolwa","year":2025,"journal":"Cureus, 17(5), e85123","doi":"10.7759/cureus.85123","pmid":"40458348","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11481","title":"Perilla frutescens Seeds as a Source of Antihypertensive Peptides: Discovery of Novel Tetrapeptides with ACE Inhibitory Activity.","authors":"Hung, Wei-Ting; Liao, Hsien-Yu; Sutopo, Christoper Caesar Yudho; Widyastuti, Endrika; Lin, Tim Chi-Chen; Hsu, Jue-Liang","year":2025,"journal":"Plant foods for human nutrition (Dordrecht, Netherlands), 80(4), 178","doi":"10.1007/s11130-025-01426-4","pmid":"41134446","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11482","title":"Antimicrobial Peptides (AMPs) Are Not Increased in Asymptomatic Bacteriuria in Healthy Older Adult Patients.","authors":"Hunold, Katherine M; Schwaderer, Andrew; Stephens, Julie A; Wexler, Randell; Camargo, Carlos A; Suer, Ozan Y; Wei, Lai; Hains, David; Southerland, Lauren T; Bischof, Jason J; Caterino, Jeffrey M","year":2025,"journal":"Journal of the American Geriatrics Society","doi":"10.1111/jgs.19431","pmid":"40062707","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11483","title":"Real-world use of tirzepatide among individuals without evidence of type 2 diabetes: Results from the Veradigm® database.","authors":"Hunter Gibble, Theresa; Chinthammit, Chanadda; Ward, Jennifer M; Cappell, Katherine; Sedgley, Robert; Bonafede, Machaon; Liao, Birong; Hankosky, Emily R","year":2025,"journal":"Diabetes, obesity & metabolism, 27(6), 3185-3194","doi":"10.1111/dom.16330","pmid":"40084533","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11484","title":"Tirzepatide Was Associated with Improved Health-Related Quality of Life in Adults with Obesity or Overweight and Type 2 Diabetes: Results from the Phase 3 SURMOUNT-2 Trial.","authors":"Hunter Gibble, Theresa; Cao, Dachuang; Zhang, Xiaotian Michelle; Xavier, Neena Agarwal; Poon, Jiat Ling; Fitch, Angela","year":2025,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 16(5), 977-991","doi":"10.1007/s13300-025-01723-w","pmid":"40120035","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11485","title":"Data mining study on adverse events of tirzepatide based on FAERS database.","authors":"Huo, Yan; Ma, Minghua; Liao, Xiaolan","year":2025,"journal":"Expert opinion on drug safety, 24(6), 675-683","doi":"10.1080/14740338.2024.2376686","pmid":"39007672","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11486","title":"Resveratrol restores glucocorticoid receptor and HDAC2 to overcome corticosteroid resistance in cigarette smoke-induced emphysema mice.","authors":"Huo, Zengyu; Chen, Xiaoli; Zheng, Guixian; Wei, Xinyan; Huang, Yanbing; Zou, Jiawei; Ou, Siyi; Xu, Cunlai; Yang, Yang; Chen, Siming; Bai, Jing","year":2025,"journal":"Journal of thoracic disease, 17(11), 9287-9299","doi":"10.21037/jtd-2025-859","pmid":"41376931","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11487","title":"Comparative Safety of Glucagon-Like Peptide 1 Receptor Agonists (GLP-1-RAs) in Type 2 Diabetes and Chronic Weight Management: A Real-World Data Study.","authors":"Hurwitz, Sarah Ruth; Lanes, Stephan; Quimbo, Tracey; Papazian, Anahit; White, Jeff; Fisher, Vicki; Cziraky, Mark J; Crowley, Matthew J; Willey, Vincent J","year":2025,"journal":"Pharmacoepidemiology and drug safety, 34(9), e70214","doi":"10.1002/pds.70214","pmid":"40947139","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11488","title":"Successful management of a calcified coronary nodule with intravenous lithotripsy: a case report and review of literature.","authors":"Hussain, Anwar; Ebrahimi, Pouya; Khan, Sohail Q; Shahid, Farhan","year":2025,"journal":"Journal of medical case reports, 19(1), 282","doi":"10.1186/s13256-025-05341-9","pmid":"40533839","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11489","title":"Breaking Biofilm Barriers: Using CATH-ICG-Loaded Bilayer Dissolving Microneedle-Assisted Photodynamic Therapy for Deep Skin Candidiasis.","authors":"Hussain, Yaseen; Dormocara, Amos; Li, Huifang; Li, Chengguo; Khan, Muhammad Kamran; Ma, Yonghao; Leng, Gang; Wang, Yipeng; You, Ben-Gang; Cui, Jing-Hao","year":2025,"journal":"Molecular pharmaceutics, 22(7), 4101-4124","doi":"10.1021/acs.molpharmaceut.5c00367","pmid":"40423575","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The novel cathelicidin peptide HcCATH-KL30 (CATH) showed potent antifungal activity against free-floating C. albicans but was ineffective against biofilm-embedded fungi. To overcome this limitation:\n\n- CATH was loaded into bilayer dissolving microneedles (DMNs) with indocyanine green (ICG) for photodynamic therapy\n- Near-infrared irradiation generated reactive oxygen species that disrupted the biofilm matrix\n- With the biofilm broken, CATH penetrated to kill the fungal cells\n- In vitro, ex vivo, and in vivo results showed ~94% reduction in fungal burden\n- Mechanism confirmed by qRT-PCR and propidium iodide staining\n\nThis is the first time this antimicrobial peptide has been explored through a drug delivery platform.","whyItMatters":"Biofilm-associated fungal infections cause serious illness, particularly in immunocompromised patients, and resist standard antifungal drugs. This dual approach — using microneedles to deliver peptides past the skin barrier and light therapy to destroy biofilm armor — tackles the two biggest obstacles to treating these infections simultaneously.","specificNumbers":"","methodology":"The cathelicidin peptide was loaded into bilayer dissolving microneedle patches containing indocyanine green as a photosensitizer. Efficacy was tested in vitro against planktonic and biofilm C. albicans, ex vivo on skin models, and in vivo in mouse models of deep dermal candidiasis. NIR irradiation was applied to activate photodynamic therapy. Mechanisms were validated through qRT-PCR gene expression analysis and propidium iodide staining for cell death.","limitations":"This is a preclinical study tested only in mouse models. The specific light exposure requirements (NIR equipment) may limit clinical practicality. Long-term safety of microneedle-delivered peptides and repeated PDT exposure in human skin was not assessed. The approach was tested against only one fungal species (C. albicans)."},{"rthcId":"RPEP-11490","title":"Effect of the GLP-1 receptor agonist exenatide on pro-inflammatory and metabolic biomarkers in individuals with alcohol use disorder: Post hoc results from a randomized, double-blinded, placebo-controlled clinical trial.","authors":"Hviid, Malthe E B; Christoffersen, Lea A N; Klausen, Mette K; Brodersen, Thorsten; Pedersen, Ole B; Ostrowski, Sisse R; Larsen, Margit H; Kongstad, Mette; Jensen, Mathias E; Vilsbøll, Tina; Fink-Jensen, Anders","year":2025,"journal":"Alcohol, clinical & experimental research, 49(8), 1659-1666","doi":"10.1111/acer.70110","pmid":"40630018","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11491","title":"Glucagon-Like Peptide 1 (GLP-1) Action on Hypothalamic Feeding Circuits.","authors":"Hwang, Eunsang; Portillo, Bryan; Williams, Kevin W","year":2025,"journal":"Endocrinology, 166(10)","doi":"10.1210/endocr/bqaf125","pmid":"40911609","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies three key hypothalamic nuclei — the arcuate nucleus, paraventricular hypothalamic area, and dorsomedial hypothalamus — as primary targets where GLP-1 signals are integrated to regulate feeding, body weight, and blood sugar. Natural GLP-1, produced by specific neurons in the brainstem (nucleus tractus solitarius), and pharmaceutical GLP-1 receptor agonists engage these circuits through both shared and distinct pathways. The authors highlight that circuit redundancy and context-dependent signaling help explain why GLP-1 drugs produce robust weight loss effects.","whyItMatters":"GLP-1 drugs like semaglutide and tirzepatide have become blockbuster obesity treatments, but scientists are still uncovering exactly how they suppress appetite in the brain. This review maps out the specific brain circuits involved, which could guide development of next-generation weight loss drugs that target these pathways more precisely with fewer side effects.","specificNumbers":"","methodology":"This is a narrative review that synthesizes recent research on GLP-1 receptor signaling in hypothalamic feeding circuits. The authors evaluated studies on both endogenous GLP-1 produced by brainstem neurons and pharmacological GLP-1 receptor agonists, proposing a conceptual framework for understanding how these signals are integrated in the brain.","limitations":"As a review paper, this study does not present new experimental data. The proposed conceptual framework, while useful for guiding research, has not been fully validated experimentally. Much of the underlying research was conducted in animal models, and the translation to human brain circuits remains an open question."},{"rthcId":"RPEP-11492","title":"Lifetime Health Effects and Cost-Effectiveness of Tirzepatide and Semaglutide in US Adults.","authors":"Hwang, Jennifer H; Laiteerapong, Neda; Huang, Elbert S; Kim, David D","year":2025,"journal":"JAMA health forum, 6(3), e245586","doi":"10.1001/jamahealthforum.2024.5586","pmid":"40085108","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11493","title":"Cyclotides as novel plant-derived scaffolds for orally active cyclic peptide therapeutics.","authors":"Hyun, Youbong","year":2025,"journal":"Molecules and cells, 48(9), 100252","doi":"10.1016/j.mocell.2025.100252","pmid":"40619067","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11494","title":"Novel and established biomarkers to complement risk scores in patients with acute decompensated heart failure - a pilot study.","authors":"Hähnel, Valentin; Meretz, Victoria; Butter, Christian; Paar, Vera; Edlinger, Christoph; Lichtenauer, Michael; Biemann, Ronald; Isermann, Berend; Hoffmeister, Meike; Haase, Michael; Haase-Fielitz, Anja; Bannehr, Marwin","year":2025,"journal":"American heart journal plus : cardiology research and practice, 53, 100544","doi":"10.1016/j.ahjo.2025.100544","pmid":"40271152","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11495","title":"Incretin Hormones GLP-1 and GIP Normalize Energy Utilization and Reduce Inflammation in the Brain in Alzheimer's Disease and Parkinson's Disease: From Repurposed GLP-1 Receptor Agonists to Novel Dual GLP-1/GIP Receptor Agonists as Potential Disease-Modifying Therapies.","authors":"Hölscher, Christian","year":2025,"journal":"CNS drugs, 39(12), 1201-1220","doi":"10.1007/s40263-025-01226-z","pmid":"40938528","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11496","title":"Phosphodiesterase-4 Inhibition as a Potential Therapeutic Strategy in the Management of Obesity: a Review.","authors":"Høck, Aske Nicolai; Olafsson, Petur Thorri; Gether, Ida M; Grøndahl, Magnus F G; Gyldenløve, Mette; Nielsen, Casper K; Lund, Asger B","year":2025,"journal":"Obesity reviews : an official journal of the International Association for the Study of Obesity, e70050","doi":"10.1111/obr.70050","pmid":"41423328","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11497","title":"Epicardial Fat Inflammation and GLP-1/GIP Receptor Analogs: Are we Shifting our Perspective?","authors":"Iacobellis, Gianluca","year":2025,"journal":"Current cardiology reports, 27(1), 161","doi":"10.1007/s11886-025-02325-5","pmid":"41307857","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"This review proposes a paradigm shift in understanding epicardial adipose tissue (EAT) inflammation: rather than being purely harmful, EAT inflammation may be a necessary process for fat tissue remodeling and an adaptive response to GLP-1 and GIP peptide drug treatment. Epicardial fat expresses both GLP-1 and GIP receptors, suggesting these peptide drugs interact directly with this cardiac fat depot.\n\nActivation of EAT GLP-1R and GIP-R may induce a beneficial balance — increasing healthy fat cell formation (adipogenesis) while reducing dangerous ectopic fat accumulation around the heart. This reframing suggests the cardiovascular benefits of liraglutide, semaglutide, and tirzepatide may be partly mediated through beneficial EAT inflammation and remodeling.","whyItMatters":"Epicardial fat is now recognized as a major driver of coronary artery disease and atrial fibrillation. Understanding that GLP-1/GIP peptide drugs can directly remodel this cardiac fat depot — and that the resulting inflammation is actually beneficial — fundamentally changes how we understand the cardiovascular protection these drugs provide. This suggests their heart benefits go beyond weight loss and blood sugar control to direct modification of the most dangerous fat in the body.","specificNumbers":"GLP-1R and GIP-R both expressed on EAT · 3 drugs discussed (liraglutide, semaglutide, tirzepatide) · EAT linked to CAD and AF · Paradigm shift from harmful to adaptive inflammation","methodology":"This is a narrative review and perspective article synthesizing evidence from studies on epicardial adipose tissue biology, GLP-1/GIP receptor expression in fat tissue, and clinical data on the cardiovascular effects of incretin-based peptide drugs.","limitations":"This is a conceptual review proposing a paradigm shift, not a study with new experimental data. The hypothesis that EAT inflammation from GLP-1/GIP drugs is beneficial rather than harmful requires direct testing. The mechanisms linking EAT receptor activation to cardiovascular outcomes are not fully established. Whether EAT remodeling is a major or minor contributor to the cardiovascular benefits of these drugs compared to other mechanisms (weight loss, glucose control, anti-atherosclerotic effects) is unknown."},{"rthcId":"RPEP-11498","title":"Liraglutide effects on epicardial adipose tissue micro-RNAs and intra-operative glucose control.","authors":"Iacobellis, Gianluca; Goldberger, Jeffrey J; Lamelas, Joseph; Martinez, Claudia A; Sterling, Carlos Munoz; Bodenstab, Monica; Frasca, Daniela","year":2025,"journal":"Nutrition, metabolism, and cardiovascular diseases : NMCD, 35(2), 103726","doi":"10.1016/j.numecd.2024.08.019","pmid":"39277531","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In all patients, miR16, miR155, and miR181a were significantly higher in coronary epicardial fat (CORO-EAT) and left atrial epicardial fat (LA-EAT) compared to subcutaneous fat (SAT). In the liraglutide group specifically, miR16 and miR181a were significantly higher in CORO-EAT vs. SAT, and miR155 and miR181a were higher in LA-EAT vs. SAT. Liraglutide-treated patients had significantly better intra-operative glucose control (146 ± 21 vs 160 ± 21 mg/dL, p<0.01) independent of weight loss.","whyItMatters":"Epicardial fat is increasingly recognized as an active contributor to heart disease — not just passive storage tissue. Understanding how GLP-1 agonists change the molecular profile of heart fat could reveal new mechanisms of cardiovascular protection. The finding that liraglutide improves surgical glucose control is immediately clinically useful for managing diabetic patients undergoing cardiac surgery.","specificNumbers":"","methodology":"Randomized, double-blind, placebo-controlled trial of 38 patients with type 2 diabetes and coronary artery disease scheduled for coronary artery bypass grafting (CABG). Patients received liraglutide or placebo for 4-12 weeks pre-operatively. During CABG, fat samples were collected from three locations: coronary epicardial fat, left atrial epicardial fat, and subcutaneous fat. MicroRNA expression (miR16, miR155, miR181a) was analyzed across locations and treatment groups.","limitations":"Small sample size (38 patients) limits statistical power and the ability to adjust for multiple comparisons. The microRNA differences between fat depots are described but their functional significance is not tested. The 4-12 week treatment window varied, introducing heterogeneity. The study measured miRNA expression but did not connect it to clinical cardiovascular outcomes. Only three miRNAs were analyzed, and a broader unbiased profiling might reveal additional changes."},{"rthcId":"RPEP-11499","title":"Combination preventive therapy with onabotulinumtoxinA and atogepant for chronic migraine: A 24-week, prospective, real-world evaluation (SYNERGY study).","authors":"Iannone, Luigi Francesco; Romozzi, Marina; Russo, Antonio; Finkelstein, Ian; Seabi, Dineo; Ahlden, Adam; Aamodt, Anne Hege; Caronna, Edoardo; Pozo-Rosich, Patricia; Tronvik, Erling Andreas; Sundal, Christina","year":2025,"journal":"Cephalalgia : an international journal of headache, 45(12), 3331024251398011","doi":"10.1177/03331024251398011","pmid":"41329703","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11500","title":"Effect of Atogepant on Sleep Quality and Sleep-Related Adverse Events in Adult Patients with Migraine: A Prospective Observational 12-Week Study.","authors":"Iannone, Luigi Francesco; Boccalini, Alberto; Lo Castro, Flavia; Brovia, Daria; Romozzi, Marina; Vernieri, Fabrizio; Altamura, Claudia; Guérzoni, Simona","year":2025,"journal":"CNS drugs, 39(12), 1341-1354","doi":"10.1007/s40263-025-01235-y","pmid":"41073685","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11501","title":"Effectiveness and tolerability of rimegepant in the acute treatment of migraine: a real-world, prospective, multicentric study (GAINER study).","authors":"Iannone, Luigi Francesco; Vaghi, Gloria; Sebastianelli, Gabriele; Casillo, Francesco; Russo, Antonio; Silvestro, Marcello; Pistoia, Francesca; Volta, Giorgio Dalla; Cortinovis, Matteo; Chiarugi, Alberto; Montisano, Danilo Antonio; Prudenzano, Maria Pia; Cevoli, Sabina; Mampreso, Edoardo; Avino, Gianluca; Romozzi, Marina; Valente, Mariarosaria; Fasano, Carla; Battistini, Stefania; Granato, Antonio; Piella, Elisa Maria; Rainero, Innocenzo; Ornello, Raffaele; De Icco, Roberto","year":2025,"journal":"The journal of headache and pain, 26(1), 4","doi":"10.1186/s10194-024-01935-8","pmid":"39762740","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11502","title":"Biomarkers of increased bleeding risk in patients with atrial fibrillation on oral anticoagulation: a narrative review.","authors":"Ibrahem, Abdalazeem; Abdalwahab, Ahmed; Gillan, Michael; Egred, Mohaned; Alkhalil, Mohammad; Gorog, Diana A; Farag, Mohamed","year":2025,"journal":"Cardiovascular diagnosis and therapy, 15(4), 876-887","doi":"10.21037/cdt-2024-696","pmid":"40948713","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11503","title":"Defatted chia (Salvia hispanica L.) flour peptides: Exploring nutritional profiles, techno-functional and bio-functional properties, and future directions.","authors":"Ibrahim Khushairay, Etty Syarmila; Yusop, Salma Mohamad; Maskat, Mohamad Yusof; Babji, Abdul Salam","year":2025,"journal":"Current research in food science, 10, 101035","doi":"10.1016/j.crfs.2025.101035","pmid":"40207205","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11504","title":"Glucagon-Like Peptide-1 Receptor Agonists Versus Bariatric Surgery in Patients With Obesity and Heart Failure With Preserved Ejection Fraction.","authors":"Ibrahim, Ramzi; Han, William; Wang, Winston; Kau, Ethan; Said, Nada; Forst, Beani; Pham, Hoang N; Abdelnabi, Mahmoud; Salih, Mohammed; Ali, Nima B; Farina, Juan; Lester, Steven J; Lee, Kwan; Ayoub, Chadi; Arsanjani, Reza","year":2025,"journal":"Journal of the American Heart Association, 14(24), e044577","doi":"10.1161/JAHA.125.044577","pmid":"41378487","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 2,747 propensity-matched patients per group (mean age 68), GLP-1 RA therapy showed significant advantages over bariatric surgery:\n\n- Acute heart failure events: 38.9% vs 44.6% (HR 0.78, 95% CI 0.72-0.85) — 22% lower\n- All-cause death: 11.1% vs 14.8% (HR 0.71, 95% CI 0.61-0.82) — 29% lower\n- All-cause hospitalizations: 66.4% vs 77.3% (HR 0.62, 95% CI 0.58-0.66) — 38% lower\n- Myocardial infarction: similar between groups (HR 0.99)\n- Stroke: similar between groups (HR 0.87, not significant)\n\nWeight loss was comparable: mean BMI at follow-up was 38.0 (GLP-1 RA) vs 37.7 (surgery), with no significant difference. However, blood sugar control was better after surgery (HbA1c 6.8 vs 7.4, P<0.001).","whyItMatters":"Heart failure with preserved ejection fraction (HFpEF) is the most common form of heart failure and is strongly linked to obesity. While bariatric surgery is effective for weight loss, it carries surgical risks and is not accessible to all patients. If GLP-1 medications can achieve equal or better cardiovascular outcomes through a non-surgical approach, it could transform how this increasingly common condition is managed — particularly for older or higher-risk patients who are poor surgical candidates.","specificNumbers":"","methodology":"Retrospective cohort study using the TriNetX multicenter research network. Adults aged 18+ with heart failure with preserved ejection fraction and obesity (BMI >30) from 2017-2022 were divided into two groups: those receiving GLP-1 RAs (semaglutide or tirzepatide) and those who underwent bariatric surgery. Propensity score matching (1:1) balanced baseline characteristics. Cox proportional hazard models estimated hazard ratios for cardiovascular outcomes.","limitations":"This is a retrospective observational study, which cannot prove causation. Despite propensity matching, unmeasured confounders may exist — including selection bias (patients who received surgery vs. medication may differ in ways not captured). The TriNetX database has inherent coding limitations. Blood sugar control was better with surgery, suggesting the two groups may have differed metabolically. The study period (2017-2022) included early semaglutide and tirzepatide adoption, which may not reflect current prescribing practices."},{"rthcId":"RPEP-11505","title":"Use of glucagon-like peptide-1 receptor agonists in patients with left ventricular assist devices.","authors":"Ibrahim, Ramzi; Nhat, Hoang; Abdelnabi, Mahmoud; Forst, Beani; Allam, Mohamed; Mee, Xuan Ci; Lim, Ghee Kheng; Bcharah, George; Barry, Timothy; Farina, Juan; Ayoub, Chadi; Arsanjani, Reza; Lee, Kwan","year":2025,"journal":"ESC heart failure, 12(6), 4326-4335","doi":"10.1002/ehf2.15379","pmid":"41078121","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11506","title":"Glucagon-Like Peptide-1 Receptor Agonists in Neurodegenerative Diseases: A Comprehensive Review.","authors":"Ibrahim, Ruba; Kambal, Aya; Abdelmajeed, Mohammed A","year":2025,"journal":"Cureus, 17(9), e92441","doi":"10.7759/cureus.92441","pmid":"40964464","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11507","title":"Assessing the Safety of Semaglutide and Tirzepatide in Black and Asian Populations: A Narrative Review.","authors":"Iftikhar, Pulwasha; Khatri, Chander P; Nanduri, Sri Ratna Divya; Ramzan, Minahil; Sakalabaktula, Krishna Sai Kiran","year":2025,"journal":"Cureus, 17(7), e87188","doi":"10.7759/cureus.87188","pmid":"40755607","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11508","title":"Endocrinology and the Lung: Exploring the Bidirectional Axis and Future Directions.","authors":"Iglesias, Pedro","year":2025,"journal":"Journal of clinical medicine, 14(19)","doi":"10.3390/jcm14196985","pmid":"41096064","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11509","title":"Real-world Efficacy of Erenumab on Migraine-associated Symptoms and Patient-reported Satisfaction Levels: A Retrospective Study in Japan.","authors":"Ihara, Keiko; Takahashi, Nobuyuki; Ohtani, Seiya; Watanabe, Narumi; Ishizuchi, Kei; Takemura, Ryo; Tokuyasu, Daiki; Sekiguchi, Koji; Miyazaki, Naoki; Imai, Shungo; Hori, Satoko; Nakahara, Jin; Takizawa, Tsubasa","year":2025,"journal":"Internal medicine (Tokyo, Japan), 64(6), 825-831","doi":"10.2169/internalmedicine.4037-24","pmid":"39111884","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11510","title":"Efficacy and safety of rimegepant for the acute treatment of migraine in Japan: A dose-ranging, double-blind, randomized controlled trial.","authors":"Ikeda, Koichi; Matsumori, Yasuhiko; Kudo, Masako; Ishikawa, Tomofumi; Hoshino, Yuko; Yoshimatsu, Hiroki; Thiry, Alexandra; Arakawa, Akio; Croop, Robert; Fullerton, Terence; Sakai, Fumihiko; Takeshima, Takao","year":2025,"journal":"Headache, 65(10), 1811-1820","doi":"10.1111/head.14994","pmid":"40586377","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11511","title":"Hexanoic Acid Improves Metabolic Health in Mice Fed High-Fat Diet.","authors":"Ikeda, Takako; Takii, Kumika; Omichi, Yuna; Nishimoto, Yuki; Ichikawa, Daisuke; Matsunaga, Tomoka; Kawauchi, Ami; Kimura, Ikuo","year":2025,"journal":"Nutrients, 17(17)","doi":"10.3390/nu17172868","pmid":"40944255","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11512","title":"Effects of Glucagon-Like Peptide-1 Receptor Agonists, Sodium-Glucose Cotransporter-2 Inhibitors, and Their Combination on Neurohumoral and Mitochondrial Activation in Patients With Diabetes.","authors":"Ikonomidis, Ignatios; Pavlidis, George; Pliouta, Loukia; Katogiannis, Konstantinos; Maratou, Eirini; Thymis, John; Michalopoulou, Eleni; Prentza, Vasiliki; Katsanaki, Eleni; Vlachomitros, Dimitrios; Kountouri, Aikaterini; Korakas, Emmanouil; Andreadou, Ioanna; Kouretas, Dimitrios; Parissis, John; Lambadiari, Vaia","year":2025,"journal":"Journal of the American Heart Association, 14(5), e039129","doi":"10.1161/JAHA.124.039129","pmid":"40008510","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11513","title":"Intravenous peptides and amino acids for erectile dysfunction: a narrative review of current applications and future directions.","authors":"Ila, Vishal; Pozzi, Edoardo; Gamage, Miyuru; Ramasamy, Ranjith","year":2025,"journal":"Expert opinion on pharmacotherapy, 26(5), 631-637","doi":"10.1080/14656566.2025.2478912","pmid":"40069591","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11514","title":"Antibiotic exposure alters the LEAP-2/ghrelin axis and anti-inflammatory tone in aged male rat liver and adipose tissue.","authors":"Ilgin, Rabia; Sayin, Oya; Ates, Mehmet; Akkaya, Erhan Caner; Hosgorler, Ferda","year":2025,"journal":"Biogerontology, 27(1), 19","doi":"10.1007/s10522-025-10368-y","pmid":"41384990","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11515","title":"Acupuncture and Kinesitherapy Improve Physical Activity More than Kinesitherapy Alone in Patients with Acute Decompensated Chronic Heart Failure with Reduced Ejection Fraction Who Are Already on Optimal Drug Therapy: A Randomized, Sham-Controlled, Double-Blind Clinical Study.","authors":"Ilic, Dejan; Jovic, Zoran; Mladenovic, Zorica; Pejovic, Vesna; Lung, Branislava; Kozic, Aleksandra; Obradovic, Slobodan","year":2025,"journal":"Biomedicines, 13(1)","doi":"10.3390/biomedicines13010176","pmid":"39857763","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11516","title":"Enhancing Stability and Bioavailability of Peptidylglycine Alpha-Amidating Monooxygenase in Circulation for Clinical Use.","authors":"Ilina, Yulia; Kaufmann, Paul; Press, Michaela; Uba, Theo Ikenna; Bergmann, Andreas","year":2025,"journal":"Biomolecules, 15(2)","doi":"10.3390/biom15020224","pmid":"40001527","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11517","title":"Medications for Weight Loss and MASLD: A National Survey of Hepatology and Gastroenterology Provider Practices, Attitudes, and Knowledge Before Resmetirom.","authors":"Im, Gene Y; Asgharpour, Amon; Aby, Elizabeth S; Stine, Jonathan G; Mellinger, Jessica L; Luther, Jay; Izzy, Manhal; Haque, Lamia; Lee, Brian T; Cotter, Thomas G; Sherman, Courtney B; Jophlin, Loretta L; Goel, Aparna; Rice, John; Chandna, Shaun; Lizaola-Mayo, Blanca; Chen, Po-Hung; Singal, Ashwani K; Bansal, Meena B","year":2025,"journal":"Journal of clinical gastroenterology","doi":"10.1097/MCG.0000000000002147","pmid":"40549581","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11518","title":"GraphCPP: The new state-of-the-art method for cell-penetrating peptide prediction via graph neural networks.","authors":"Imre, Attila; Balogh, Balázs; Mándity, István","year":2025,"journal":"British journal of pharmacology, 182(3), 495-509","doi":"10.1111/bph.17388","pmid":"39568115","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11519","title":"Real-World Sex Differences in Response to Treatment with Glucagon-like Peptide-1 Receptor Agonists: Analysis of Single-Center Outpatient Case Series.","authors":"Inceu, Georgeta Victoria; Crăciun, Anca-Elena; Ciobanu, Dana Mihaela; Berchisan, Antonia; Fodor, Adriana; Bala, Cornelia; Roman, Gabriela; Rusu, Adriana","year":2025,"journal":"Medicina (Kaunas, Lithuania), 61(8)","doi":"10.3390/medicina61081343","pmid":"40870388","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11520","title":"Unveiling the Therapeutic Potential of the Second-Generation Incretin Analogs Semaglutide and Tirzepatide in Type 1 Diabetes and Latent Autoimmune Diabetes in Adults.","authors":"Infante, Marco; Silvestri, Francesca; Padilla, Nathalia; Pacifici, Francesca; Pastore, Donatella; Pinheiro, Marcelo Maia; Caprio, Massimiliano; Tesauro, Manfredi; Fabbri, Andrea; Novelli, Giuseppe; Alejandro, Rodolfo; De Lorenzo, Antonino; Ricordi, Camillo; Della-Morte, David","year":2025,"journal":"Journal of clinical medicine, 14(4)","doi":"10.3390/jcm14041303","pmid":"40004833","tags":["GLP-1-agonists","type-1-diabetes"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Semaglutide and tirzepatide — originally developed for type 2 diabetes and obesity — show promise as add-on treatments to insulin in type 1 diabetes (T1D), double diabetes, and latent autoimmune diabetes in adults (LADA). Evidence from mostly real-world studies suggests these GLP-1-based drugs improve glucose control, promote weight loss, may preserve remaining beta-cell function, and provide additional metabolic benefits in T1D patients.\n\nThe concept of 'double diabetes' — T1D patients who also develop insulin resistance, obesity, or metabolic syndrome — is emerging as a significant clinical challenge. Neither semaglutide nor tirzepatide is currently approved for T1D, but off-label use is growing as overweight and obesity increasingly affect T1D populations.","whyItMatters":"Type 1 diabetes treatment has been stuck on insulin-only therapy for a century. As T1D patients increasingly struggle with the same obesity and metabolic problems as the general population, the potential to add GLP-1 drugs to their treatment could be transformative — reducing insulin doses, controlling weight, and potentially slowing the autoimmune destruction of remaining beta cells. This represents a paradigm shift in how T1D might be managed.","specificNumbers":"Not approved for T1D · growing real-world evidence · targets T1D + double diabetes + LADA populations","methodology":"Comprehensive review of available literature — primarily real-world studies, case reports, and small clinical trials — on the safety and efficacy of semaglutide and tirzepatide used in type 1 diabetes, double diabetes, and LADA patients.","limitations":"The evidence base is mostly real-world studies and case reports rather than large randomized controlled trials. Neither drug is approved for T1D, and off-label use introduces selection bias. Long-term safety in T1D patients — particularly regarding DKA risk and beta-cell preservation — needs more rigorous study. Hypoglycemia risk when combining GLP-1 drugs with insulin requires careful management."},{"rthcId":"RPEP-11521","title":"Multidisciplinary care of pediatric obesity and its impact on sleep: a review.","authors":"Inja, Ravali; Cielo, Christopher","year":2025,"journal":"Frontiers in sleep, 4, 1634185","doi":"10.3389/frsle.2025.1634185","pmid":"41550266","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies obstructive sleep apnea (OSA) and obesity hypoventilation syndrome (OHS) as serious sleep-related comorbidities in obese children, often coexisting with insulin resistance, type 2 diabetes, hypertension, and non-alcoholic fatty liver disease.\n\nGLP-1 receptor agonists are highlighted as a promising pharmacologic intervention for pediatric obesity, but the review concludes that their use in children remains constrained by limited data — particularly regarding their impact on sleep disorders. The authors emphasize that it is currently unclear whether GLP-1 agonist-induced weight loss translates into improvements in OSA, OHS, or related outcomes like cognitive function and psychosocial wellbeing in pediatric populations.","whyItMatters":"Pediatric obesity rates are rising globally, and sleep disorders in obese children have cascading effects on development, learning, and long-term cardiovascular health. As GLP-1 drugs begin to be used in children, understanding whether they improve sleep — not just weight — is essential for comprehensive pediatric care. This review highlights a significant evidence gap that could shape how these peptide drugs are prescribed and studied in children.","specificNumbers":"","methodology":"Narrative review synthesizing literature on pediatric obesity, its sleep-related comorbidities, and available treatment approaches including lifestyle interventions, GLP-1 receptor agonists, and bariatric surgery. The review examines global trends, academic performance impacts, and the role of multidisciplinary wellbeing clinics.","limitations":"This is a narrative review without systematic search methodology or meta-analytic pooling. It does not present new data. The discussion of GLP-1 agonists in pediatrics is limited by the scarcity of published studies in this population. The review does not provide specific efficacy data for GLP-1 drugs in children or quantify their effects on sleep outcomes."},{"rthcId":"RPEP-11522","title":"Dulaglutide use to improve binge eating behaviors in a person with type 2 diabetes and obesity.","authors":"Innocent, Britnee; Elmaoued, Amre A; Cowart, Kevin; White, Raechel T","year":2025,"journal":"American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists, 82(16), 886-890","doi":"10.1093/ajhp/zxaf088","pmid":"40220283","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A patient with mild binge eating disorder, type 2 diabetes, and obesity was treated with dulaglutide 0.75 mg weekly. At 6-week follow-up, improvements were observed in the Binge Eating Scale (BES) score, BMI, body weight, and BED symptoms. Dulaglutide was well tolerated with no reported adverse drug events.\n\nWhile dulaglutide was initiated for diabetes management, the concurrent improvement in binge eating behaviors suggests GLP-1 receptor agonists may have dual benefits in patients with comorbid BED and metabolic conditions. The case adds to an emerging evidence base for GLP-1 drugs in eating disorders, though the mechanism — whether through appetite suppression, reward pathway modulation, or both — requires further investigation.","whyItMatters":"Binge eating disorder is the most common eating disorder in the United States, yet treatment options are limited and often ineffective. GLP-1 drugs like dulaglutide work on brain pathways that control appetite and reward — the same pathways implicated in binge eating. If GLP-1 drugs prove effective for BED, they could offer a novel treatment approach that addresses both the eating disorder and common metabolic comorbidities like diabetes and obesity simultaneously.","specificNumbers":"","methodology":"This is a single-patient case report. Baseline measurements included binge eating scale (BES) score, glycated hemoglobin (HbA1c), BMI, and body weight. Dulaglutide 0.75 mg was administered subcutaneously once weekly. Follow-up assessments at 6 weeks evaluated changes in all baseline parameters and documented any adverse events.","limitations":"This is a single case report, the lowest level of clinical evidence. No causal conclusions can be drawn — the improvements could be coincidental, related to placebo effect, or driven by other factors in the patient's life. The 6-week follow-up is very short; long-term BED outcomes are unknown. The low dulaglutide dose (0.75 mg vs up to 4.5 mg) may not represent the optimal dose for BED. The patient had mild BED; results may not generalize to moderate or severe cases."},{"rthcId":"RPEP-11523","title":"Glucagon-Like Peptide-1 Receptor Agonists and Incidence of Dementia Among Older Adults With Type 2 Diabetes : A Target Trial Emulation.","authors":"Inoue, Kosuke; Saliba, Debra; Gotanda, Hiroshi; Moin, Tannaz; Mangione, Carol M; Klomhaus, Alexandra M; Tsugawa, Yusuke","year":2025,"journal":"Annals of internal medicine, 178(9), 1258-1267","doi":"10.7326/ANNALS-24-02648","pmid":"40690769","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11524","title":"Establishment of reliable identification algorithms for acute heart failure or acute exacerbation of chronic heart failure using clinical data from a medical information database network.","authors":"Inoue, Ryusuke; Nakayama, Masaharu; Ota, Hideki; Nakamura, Naoki; Fujii, Susumu; Ishii, Akira; Saito, Atsuko; Suzuki, Takahiro; Nomura, Hiroko; Goto, Natsuko; Watanabe, Shinya; Maruyama, Hotaka; Nozawa, Mayu; Uyama, Yoshiaki","year":2025,"journal":"Frontiers in cardiovascular medicine, 12, 1642323","doi":"10.3389/fcvm.2025.1642323","pmid":"41169881","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11525","title":"Finerenone ameliorates diabetic kidney disease exacerbated by deletion of natriuretic peptide/guanylyl cyclase-A signaling and dietary high-protein load.","authors":"Inoue, Yui; Ishii, Akira; Ishimura, Takuya; Yamada, Hiroyuki; Sugioka, Sayaka; Handa, Takaya; Ikushima, Akie; Nishio, Haruomi; Kato, Yukiko; Ohno, Shoko; Nakagawa, Yasuaki; Kuwahara, Koichiro; Matsusaka, Taiji; Tokudome, Takeshi; Yanagita, Motoko; Yokoi, Hideki","year":2025,"journal":"Scientific reports, 15(1), 41378","doi":"10.1038/s41598-025-25362-0","pmid":"41271924","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11526","title":"Expression of Concern: Paladugu et al. Liraglutide Has Anti-Inflammatory and Anti-Amyloid Properties in Streptozotocin-Induced and 5xFAD Mouse Models of Alzheimer's Disease. Int. J. Mol. Sci. 2021, 22, 860.","authors":"Internation Journal Of Molecular Sciences Editorial Office","year":2025,"journal":"International journal of molecular sciences, 26(10)","doi":"10.3390/ijms26104467","pmid":"40429612","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11527","title":"Cardiovascular Events in Adults with Type 2 Diabetes and ASCVD Initiating Once-Weekly Semaglutide vs DPP-4is in the USA.","authors":"Inzucchi, Silvio E; Tan, Xi; Liang, Yuanjie; Yedigarova, Larisa; Xie, Lin; de Havenon, Adam","year":2025,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 16(2), 187-203","doi":"10.1007/s13300-024-01678-4","pmid":"39688779","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11528","title":"Stress and high fat diet reconfigure the active translatome of CeA-NPY neurons.","authors":"Ip, Chi Kin; Zhang, Lei; Tasan, Ramon; Herzog, Herbert","year":2025,"journal":"Molecular metabolism, 98, 102176","doi":"10.1016/j.molmet.2025.102176","pmid":"40480630","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"TRAPseq profiling revealed that NPY neurons in the central amygdala co-express orexigenic (appetite-stimulating) gene markers while showing minimal overlap with anorexigenic markers, confirming their role as hunger-promoting cells. Under combined high-fat diet and stress (HFDS), distinct gene clusters activated involving fatty acid metabolism, stress response pathways, and feeding-related neuropeptide production.\n\nImmunohistochemistry revealed long-range projections from CeA NPY neurons to the lateral habenula, periaqueductal gray, and parvicellular reticular formation — brain regions involved in reward, pain, and motor responses. Lipid-sensing mechanisms and synaptic modulating pathways were identified as principal stress targets within the CeA-NPY circuit.","whyItMatters":"Stress-driven overeating is a major driver of the obesity epidemic, but the molecular mechanisms have been unclear. By revealing exactly how NPY neurons reprogram their protein production under stress + high-fat conditions, this study identifies specific molecular targets — lipid sensors and synaptic modulators — that could be targeted by future anti-obesity therapies addressing the root neurobiological cause of stress eating.","specificNumbers":"","methodology":"Researchers used translational ribosome affinity purification coupled with next-generation sequencing (TRAPseq) to identify RNA transcripts actively being translated into proteins specifically in NPY neurons. Mice were exposed to high-fat diet alone or high-fat diet combined with chronic stress. Gene ontology analysis identified functional pathway clusters, and immunohistochemistry mapped NPY neuron projections throughout the brain.","limitations":"This is a mouse study using a specific genetic NPY neuron labeling approach, and the molecular changes may not directly translate to human brains. The study characterized molecular profiles and neuronal projections but did not test whether blocking the identified pathways would prevent stress-induced weight gain. Chronic stress models in mice may not fully replicate the psychological complexity of human stress eating."},{"rthcId":"RPEP-11529","title":"Neuropeptide-Mediated Crosstalk between Subchondral Bone and Articular Cartilage in Ankle Osteoarthritis: A Cross-Sectional Histologic Study of 17 Ankles.","authors":"Ishibashi, Saori; Nakasa, Tomoyuki; Ikuta, Yasunari; Sakurai, Satoru; Moriwaki, Dan; Chujo, Taro; Adachi, Nobuo","year":2025,"journal":"Foot & ankle international, 46(11), 1311-1321","doi":"10.1177/10711007251372141","pmid":"41104509","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 17 ankle joints from OA patients, CGRP and substance P expression were significantly upregulated in sclerotic subchondral bone. Both neuropeptides showed strong positive correlations with:\n- Hounsfield unit (HU) values (bone density on CT)\n- Subchondral bone plate thickness\n- Modified Mankin scores (cartilage degeneration severity)\n\nCGRP expression appeared earlier than substance P, detectable at moderate degeneration stages. TRAP-positive osteoclast numbers also increased with disease progression and followed a distribution pattern matching CGRP and SP expression, suggesting a functional relationship between neuropeptide signaling and bone remodeling.","whyItMatters":"This is the first study to systematically map neuropeptide expression in subchondral bone specifically in ankle OA, revealing that the bone itself — not just the joint lining or cartilage — is a source of pain-related neuropeptides. The finding that CGRP appears before substance P suggests it may serve as an earlier biomarker or therapeutic target. The link between neuropeptides and osteoclast activity opens the possibility that pain signaling and bone destruction are mechanistically connected, not just coincidental.","specificNumbers":"","methodology":"Seventeen ankles from 16 patients who underwent total ankle arthroplasty for OA were analyzed. Researchers conducted radiographic evaluation, CT imaging with Hounsfield unit measurements, and histologic analysis including subchondral bone plate thickness and trabecular bone area measurements. Cartilage degeneration was scored using modified Mankin criteria. Immunohistochemistry was performed for CGRP, substance P, collagen types I, II, and X, and TRAP staining identified osteoclasts. Correlations between neuropeptide expression and structural/degenerative parameters were analyzed.","limitations":"This is a cross-sectional study, meaning it captures one timepoint and cannot establish whether neuropeptide upregulation causes or results from bone changes and cartilage degeneration. The sample size is small (17 ankles from 16 patients). All specimens came from end-stage OA requiring arthroplasty, so findings may not represent earlier disease stages. The study is specific to ankle OA and may not generalize to hip or knee OA. Quantitative neuropeptide measurements were not performed — only immunohistochemical staining patterns."},{"rthcId":"RPEP-11530","title":"Integrating pre-ablation and post-ablation B-type natriuretic peptide to identify high-risk population for long-term adverse events and arrhythmic recurrence in persistent atrial fibrillation.","authors":"Ishiguchi, Hironori; Yoshiga, Yasuhiro; Fukuda, Masakazu; Fujii, Shohei; Hisaoka, Masahiro; Hashimoto, Shintaro; Omuro, Takuya; Fukue, Noriko; Kobayashi, Shigeki; Sano, Motoaki","year":2025,"journal":"Open heart, 12(1)","doi":"10.1136/openhrt-2025-003251","pmid":"40021208","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11531","title":"The impact of oral semaglutide on glycemic control and weight reduction: a database analysis of dosing effects in Japanese individuals with type 2 diabetes.","authors":"Ishiguro, Mizuki; Nishimura, Rimei","year":2025,"journal":"Frontiers in endocrinology, 16, 1615516","doi":"10.3389/fendo.2025.1615516","pmid":"40933382","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11532","title":"Effects of patient age on the therapeutic effects of GIP/GLP-1 receptor agonists (tirzepatide).","authors":"Ishimura, Atsushi; Shimizu, Yutaka; Yabuki, Naohiro","year":2025,"journal":"Drug discoveries & therapeutics, 19(2), 133-135","doi":"10.5582/ddt.2025.01012","pmid":"40301081","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11533","title":"Self-assembling peptide hydrogel scaffold accelerates healing of patellar tendon injury: A histological and biomechanical study.","authors":"Ishitani, Takashi; Otsuki, Shuhei; Yamauchi, Shota; Okamoto, Yoshinori; Wakama, Hitoshi; Sezaki, Shunsuke; Matsuyama, Junya; Nakamura, Kaito; Iwata, Takeru; Hirota, Chuji; Hirano, Yoshiaki","year":2025,"journal":"Journal of biomaterials applications, 39(8), 880-890","doi":"10.1177/08853282241299212","pmid":"39499960","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11534","title":"Acute Functional Gastric Outlet Obstruction Associated With Low-Dose Tirzepatide.","authors":"Iskander, Mina; Wadhwa, Manish; Kim, Yeongjin; Singh, Neha; Pathak, Prutha","year":2025,"journal":"Cureus, 17(1), e78090","doi":"10.7759/cureus.78090","pmid":"40026949","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11535","title":"Gastrointestinal adverse events associated with GLP-1 RA in non-diabetic patients with overweight or obesity: a systematic review and network meta-analysis.","authors":"Ismaiel, Abdulrahman; Scarlata, Giuseppe Guido Maria; Boitos, Irina; Leucuta, Daniel-Corneliu; Popa, Stefan-Lucian; Al Srouji, Nahlah; Abenavoli, Ludovico; Dumitrascu, Dan L","year":2025,"journal":"International journal of obesity (2005), 49(10), 1946-1957","doi":"10.1038/s41366-025-01859-6","pmid":"40804463","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11536","title":"Glucagon-like peptide-1 receptor agonists: Evolution, gastrointestinal adverse effects, and future directions.","authors":"Ismail, Alaa; Amer, Mohab Sherif; Tawheed, Ahmed","year":2025,"journal":"World journal of gastrointestinal pharmacology and therapeutics, 16(3), 107148","doi":"10.4292/wjgpt.v16.i3.107148","pmid":"40937289","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11537","title":"Exploring the Association Between Myocardial Infarction and Cognitive Decline: A Narrative Review.","authors":"Issimdar, Iqrah A; Mudegowdar, Rohit; Gupta, Anchal R; Patel, Keval B; Elshoura, Anas; Bhanushali, Vidhi Mahendra; Joseph, Joshua R; Meiyalagan Varalakshmi, Aishwarrya; Sahotra, Monika; Kashif, Mazin; Binny, Vivasvat; Pathan, Nahila A; Siddiqui, Humza F","year":2025,"journal":"Cureus, 17(5), e84957","doi":"10.7759/cureus.84957","pmid":"40585705","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11538","title":"Programmable Antigen-Specific Immunity via Self-Adjuvanting Nanovaccines Co-Delivering Immune Modulators.","authors":"Ito, Keita; Manabe, Yoshiyuki; Ohshima, Shino; Maeki, Masatoshi; Tokeshi, Manabu; Inaba, Hiroshi; Matsuura, Kazunori; Kabayama, Kazuya; Kametani, Yoshie; Fukase, Koichi","year":2025,"journal":"Angewandte Chemie (International ed. in English), e20474","doi":"10.1002/anie.202520474","pmid":"41403359","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The CH401 antigenic peptide was conjugated with the adjuvant Pam3CSK4 and formulated into cationic lipid nanoparticles (LNPs) smaller than 100 nm using a precision microflow device (iLiNP). This system enabled size-controlled formulation and systematic optimization of the vaccine platform.\n\nThe self-adjuvanting peptide-LNP vaccines demonstrated enhanced immunogenicity with precise modulation of antigen-specific immune responses. Supplemental adjuvants could be incorporated to further fine-tune immune activation. The vaccines elicited potent immune responses in humanized mouse models, supporting translational potential for human application.","whyItMatters":"Cancer peptide vaccines have long been limited by weak immunogenicity — they present the right targets but don't generate strong enough immune responses for clinical benefit. This platform addresses the core problem by creating self-adjuvanting nanoparticle vaccines where the peptide antigen and immune stimulator are physically linked. The ability to precisely control particle size and fine-tune immune responses through modular adjuvant combinations represents a significant step toward clinically effective peptide cancer vaccines.","specificNumbers":"","methodology":"The cancer peptide antigen CH401 was chemically conjugated with the Toll-like receptor agonist adjuvant Pam3CSK4. The conjugates were formulated into cationic lipid nanoparticles using the iLiNP microflow device, enabling precise size control (<100 nm). Various supplemental adjuvants were incorporated to modulate immune response profiles. Vaccine candidates were tested in humanized mouse models to assess antigen-specific immune responses.","limitations":"The study was conducted in humanized mouse models, which approximate but do not perfectly replicate human immune responses. Only one peptide antigen (CH401) was tested. No actual anti-tumor efficacy (tumor shrinkage or survival) data are reported in the abstract — only immune response measurements. Long-term durability of immune responses was not assessed. The manufacturing complexity of peptide-adjuvant conjugation and precision nanoparticle formulation may pose scale-up challenges."},{"rthcId":"RPEP-11539","title":"Acute Kidney Injury from Mononuclear Cell-Predominated Interstitial Nephritis After Introduction of a Glucagon-Like Peptide-1 Receptor Agonist: A Case Report.","authors":"Itsathitpaisarn, Raweekarn; Suksawad, Nattavong; Wongwikrom, Watsapol; Surintrspanont, Jerasit; Thongsricome, Thana","year":2025,"journal":"The American journal of case reports, 26, e949913","doi":"10.12659/AJCR.949913","pmid":"41353763","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A 63-year-old woman with stage 3b diabetic kidney disease was prescribed dulaglutide 0.75 mg/week due to persistent albuminuria despite maximum tolerated dose of azilsartan. At 2-month follow-up, serum creatinine increased and subsequently doubled. No other causes of kidney injury (including volume depletion) were identified.\n\nKidney biopsy revealed active mononuclear cell-predominated interstitial nephritis alongside diabetic nephropathy, without immune complex accumulation. After discontinuing dulaglutide, kidney function achieved almost complete recovery without steroid therapy. The patient was successfully rechallenged with azilsartan and chlorthalidone, confirming dulaglutide as the causative agent.","whyItMatters":"As GLP-1 receptor agonists are increasingly prescribed for diabetic kidney disease specifically because of their renal protective effects, clinicians must remain aware that rare adverse kidney reactions can occur. This case demonstrates that interstitial nephritis — though uncommon — should be considered when kidney function unexpectedly worsens after GLP-1 RA initiation. Early recognition and drug discontinuation led to near-complete recovery, underscoring the importance of monitoring.","specificNumbers":"","methodology":"This is a clinical case report of a single patient. The diagnostic workup included serial serum creatinine monitoring, evaluation and exclusion of other nephrotoxic causes, and kidney biopsy with histopathological analysis. The clinical response to dulaglutide discontinuation (drug dechallenge) and successful rechallenge with other medications provided evidence of causality.","limitations":"This is a single case report — the lowest level of clinical evidence. A definitive causal link between dulaglutide and the interstitial nephritis cannot be established from one patient. The biopsy showed coexisting diabetic nephropathy, complicating the attribution. No formal drug rechallenge with dulaglutide was performed (only other medications were rechallenged). The mechanism by which GLP-1 RAs might trigger interstitial nephritis is not understood."},{"rthcId":"RPEP-11540","title":"Overview of Epitalon-Highly Bioactive Pineal Tetrapeptide with Promising Properties.","authors":"Ivko, Olga M; Linkova, Natalia S; Ilina, Anna R; Khavinson, Vladimir Kh","year":2025,"journal":"Molecules (Basel, Switzerland), 30(6)","doi":"10.3390/molecules30061334","pmid":"40141333","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11541","title":"Bovine Milk Protein-Derived Preparations and Their Hydrolysates as Sources of ACE-Inhibitory, DPP-IV-Inhibitory, and Antioxidative Peptides Analyzed Using in Silico and in Vitro Protocols.","authors":"Iwaniak, Anna; Minkiewicz, Piotr; Mogut, Damir; Borawska-Dziadkiewicz, Justyna; Żulewska, Justyna; Darewicz, Małgorzata","year":2025,"journal":"International journal of molecular sciences, 26(9)","doi":"10.3390/ijms26094323","pmid":"40362559","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11542","title":"A Comprehensive Analysis of Diabetic Complications and Advances in Management Strategies.","authors":"Iwasaki, Hitoshi; Yagyu, Hiroaki; Shimano, Hitoshi","year":2025,"journal":"Journal of atherosclerosis and thrombosis, 32(5), 550-559","doi":"10.5551/jat.65551","pmid":"39805627","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11543","title":"Exogenous oral application of PYY and exendin-4 impacts upon taste-related behavior and taste perception in wild-type mice.","authors":"Iyer, Satya; Montmayeur, Jean-Pierre; Zolotukhin, Sergei; Dotson, Cedrick D","year":2025,"journal":"Neuropharmacology, 272, 110408","doi":"10.1016/j.neuropharm.2025.110408","pmid":"40086622","tags":["glp-1-receptor-agonists","neuropeptides"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Using adeno-associated virus vectors to deliver PYY and exendin-4 encoding genes to the salivary glands of wild-type male mice, researchers found that oral presence of these satiety peptides significantly altered taste-related behavioral responsiveness across multiple taste qualities. In vitro experiments on isolated taste bud cells confirmed that PYY and exendin-4 directly influence the responsiveness of these primary sensory cells.\n\nThis builds on previous work showing that PYY knockout mice had altered taste responsiveness and that restoring PYY expression in salivary glands rescued normal taste behavior. The current study extends these findings to normal mice with intact peptide signaling, demonstrating that exogenous peptide application can modulate taste even when the endogenous system is already functional.","whyItMatters":"Millions of people now take GLP-1 receptor agonists like semaglutide and report changes in how food tastes or reduced interest in certain foods. This study offers a biological explanation: GLP-1 pathway signaling can directly modulate taste bud cells. If satiety peptides don't just suppress appetite centrally but also change peripheral taste perception, it opens an entirely new dimension of how these drugs affect eating behavior — and potentially a new target for food intake modulation.","specificNumbers":"Significant effect on multiple taste qualities; in vitro taste bud cell responsiveness changes","methodology":"Researchers used adeno-associated virus (AAV) gene therapy to deliver genes encoding exendin-4 (a GLP-1 receptor agonist) and/or PYY to the salivary glands of male wild-type C57BL mice. This caused the mice to produce these peptides in their saliva, delivering them directly to taste buds during feeding. Taste responsiveness was measured using behavioral assays across multiple taste qualities. Additionally, the researchers tested the direct effects of these peptides on isolated taste bud cells in vitro.","limitations":"Only male mice were studied, so sex-specific differences in taste modulation are unknown. The AAV gene therapy delivery method is a research tool, not a clinically translatable approach. The abstract doesn't report specific quantitative data on the magnitude of taste changes. The study can't distinguish how much of the observed effect comes from PYY versus exendin-4 individually versus their combination."},{"rthcId":"RPEP-11544","title":"Saying no to weight-loss drugs: The paradox of the ideal patient-consumer and stratified biomedicalization.","authors":"Jackson, Ni'Shele","year":2025,"journal":"Social science & medicine (1982), 384, 118429","doi":"10.1016/j.socscimed.2025.118429","pmid":"40961640","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11545","title":"Combating Antimicrobial Resistance: Innovative Strategies Using Peptides, Nanotechnology, Phages, Quorum Sensing Interference, and CRISPR-Cas Systems.","authors":"Jacobowski, Ana Cristina; Boleti, Ana Paula Araújo; Cruz, Maurício Vicente; Santos, Kristiane Fanti Del Pino; de Andrade, Lucas Rannier Melo; Frihling, Breno Emanuel Farias; Migliolo, Ludovico; Paiva, Patrícia Maria Guedes; Teodoro, Paulo Eduardo; Teodoro, Larissa Pereira Ribeiro; Macedo, Maria Lígia Rodrigues","year":2025,"journal":"Pharmaceuticals (Basel, Switzerland), 18(8)","doi":"10.3390/ph18081119","pmid":"40872511","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11546","title":"Heart Failure Masked as Pulmonary Embolism in Non-adherent Patient With Atrial Fibrillation: Case Report and Analytical Review of the Literature.","authors":"Jacobs, Gian; Emblin, Kate; Kadam, Umesh; Daniels, Rob; Alallan, Mohammad; Mokbel, Kinan","year":2025,"journal":"In vivo (Athens, Greece), 39(1), 548-558","doi":"10.21873/invivo.13859","pmid":"39740893","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11547","title":"Exploratory safety investigations in normal, freely moving Göttingen Minipigs using telemetry: Pharmacological validation.","authors":"Jacobsen, Julie; Christoffersen, Berit Ø","year":2025,"journal":"Journal of pharmacological and toxicological methods, 136, 108395","doi":"10.1016/j.vascn.2025.108395","pmid":"40934983","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In telemetry-implanted Göttingen minipigs (n=6-8 per study):\n\n- Liraglutide (3 nmol/kg, Day 7): significant HR increase (P<0.01), no BP changes — matching human clinical observations\n- MC4 receptor agonist LY2112688 (0.1-0.15 mg/kg, Day 4): significant increases in HR (P<0.05), MAP (P<0.01), SBP (P<0.01), and DBP (P<0.05) — matching the hypertensive effect that halted MC4RA clinical development\n- Urocortin-2 infusion: significant HR increase (P<0.05) and SBP decrease (P<0.05) — matching known vasodilatory effects in humans\n\nAll three peptides qualitatively reproduced their known human cardiovascular profiles, though absolute magnitudes may differ between species.","whyItMatters":"Cardiovascular side effects are a leading cause of drug failure. The MC4 receptor agonist class, for example, was largely abandoned due to blood pressure increases discovered in clinical trials. Having a reliable animal model that catches these issues early could save years of development time and protect human trial participants.","specificNumbers":"","methodology":"Three consecutive crossover studies in female Göttingen minipigs with surgically implanted telemetry devices measured mean arterial, systolic, and diastolic blood pressure, heart rate, activity, and body temperature. Each of the three peptide compounds was tested against vehicle control in the same animals.","limitations":"Small sample sizes (6-8 animals per study). Only female minipigs were used. While qualitative effects matched human data, the quantitative magnitudes may differ between species. The study tested only three compounds, all with known cardiovascular profiles. The model's predictive value for peptides with unknown cardiovascular effects remains to be demonstrated."},{"rthcId":"RPEP-11548","title":"CagriSema drives weight loss in rats by reducing energy intake and preserving energy expenditure.","authors":"Jacobsen, Julie Mie; Halling, Jens Frey; Blom, Ida; Moreno Martinez, Jaime; Hald, Bjørn; Pedersen, Kent; Fels, Johannes Josef; Snitker, Søren; Secher, Anna; Lundh, Sofia; le Roux, Carel W; Raun, Kirsten; Reitman, Marc L; Kuhre, Rune Ehrenreich","year":2025,"journal":"Nature metabolism, 7(7), 1322-1329","doi":"10.1038/s42255-025-01324-8","pmid":"40629149","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11549","title":"GLP-1 Receptor Agonists as a Novel Solution for Antipsychotic-Induced Weight Gain in Severe and Persistent Mental Illness.","authors":"Jacobson, Samantha; Margolese, Noah; Margolese, Howard C","year":2025,"journal":"Canadian journal of psychiatry. Revue canadienne de psychiatrie, 7067437251386626","doi":"10.1177/07067437251386626","pmid":"41091899","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11550","title":"Highly sensitive LC-MRM workflow for quantitation of efflux transporters in rat peripheral blood mononuclear cells: leveraging ProteoExcelTP with MRM prediction capability.","authors":"Jadav, Tarang; Rajput, Niraj; Sengupta, Pinaki","year":2025,"journal":"The Analyst, 150(5), 998-1011","doi":"10.1039/d4an01514b","pmid":"39927836","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11551","title":"From weight loss to muscle loss: rhabdomyolysis linked to semaglutide.","authors":"Jadvani, Rutvikkumar; Singh, Meenu","year":2025,"journal":"Clinical kidney journal, 18(12), sfaf356","doi":"10.1093/ckj/sfaf356","pmid":"41383908","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11552","title":"Hydroxypropyl β cyclodextrins effects on self-assembly of cyclic peptide, lanreotide acetate, in water and subsequent release rate from an in vitro emulator of subcutaneous delivery.","authors":"Jafari, Negar; Addison, Camille; Lou, Hao; Hageman, Michael J","year":2025,"journal":"Journal of pharmaceutical sciences, 114(2), 1068-1076","doi":"10.1016/j.xphs.2024.11.018","pmid":"39615879","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11553","title":"GABA and GLP-1 receptor agonist combination therapy modifies diabetes and Langerhans islet cytoarchitecture in a rat model of Wolfram syndrome.","authors":"Jagomäe, Toomas; Velling, Sandra; Tikva, Tessa Britt; Maksimtšuk, Varvara; Gaur, Nayana; Reimets, Riin; Kaasik, Allen; Vasar, Eero; Plaas, Mario","year":2025,"journal":"Diabetology & metabolic syndrome, 17(1), 82","doi":"10.1186/s13098-025-01651-6","pmid":"40050934","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In Wolfram syndrome rats, GABA monotherapy had no significant effect on diabetes, while liraglutide monotherapy (0.4 mg/kg/day) effectively delayed progression. However, the GABA (1 g/kg/day) plus liraglutide combination reversed the diabetic phenotype entirely: glucose homeostasis was significantly enhanced, insulin and C-peptide secretion improved, and beta-cell mass increased.\n\nRemarkably, the combination therapy fully restored Langerhans islet architecture, correcting the intra-islet ratio of alpha, beta, and delta cells to normal proportions. Both liraglutide alone and combination therapy increased GAD65/67-positive beta cells, indicating improved beta-cell health, but only the combination achieved complete phenotype reversal.","whyItMatters":"Wolfram syndrome currently has no approved treatments, and patients face progressive diabetes, blindness, and neurodegeneration. Finding that a readily available combination — a GLP-1 drug already on the market plus GABA (a dietary supplement) — can reverse the diabetic phenotype and restore pancreatic tissue offers hope for a condition that has had virtually no therapeutic options.","specificNumbers":"","methodology":"Five-month-old glucose-intolerant Wolfram syndrome rats and wild-type littermates received daily treatment with GABA (1 g/kg/day), liraglutide (0.4 mg/kg/day), or both for four months. Diabetes was monitored via intraperitoneal glucose tolerance tests with insulin and hormone measurements by ELISA. Post-treatment immunohistochemistry assessed islet morphology, cellular distribution, and beta-cell health markers.","limitations":"This is a rat model study, and Wolfram syndrome in rats may not perfectly replicate the human disease. The sample sizes typical of rare disease animal models are small. Four months of treatment may not predict lifelong outcomes. GABA dosing at 1 g/kg/day is very high and may not be practical in humans. The mechanisms underlying the synergistic effect were not fully elucidated."},{"rthcId":"RPEP-11554","title":"Exploring the Interaction of RBD with Human β Defensin Type 2 Point Mutants: Insights from Molecular Dynamics Simulations.","authors":"Jahan, Ishrat; Zhang, Liqun","year":2025,"journal":"The journal of physical chemistry. B, 129(7), 1927-1933","doi":"10.1021/acs.jpcb.4c07004","pmid":"39929747","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11555","title":"Rational design of thrombin-derived VFR12 analogs with enhanced antimicrobial, antibiofilm, and anti-inflammatory properties.","authors":"Jahan, Ishrat; Kumar, S Dinesh; Ajish, Chelladurai; Lee, Chul Won; Shin, Song Yub; Yang, Sungtae","year":2025,"journal":"Scientific reports, 15(1), 40876","doi":"10.1038/s41598-025-24789-9","pmid":"41258221","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11556","title":"Peptide-Functionalized Nanopillared Surfaces with Tunable Antimicrobial and Immunomodulatory Properties.","authors":"Jahan, Samin; Bhayo, Adnan Murad; Uchida, Haruki; Ikeda, Rui; Combita, Diego; Nazeer, Nauman; Kotsuchibashi, Yohei; Ahmed, Marya","year":2025,"journal":"ACS omega, 10(46), 56680-56691","doi":"10.1021/acsomega.5c09250","pmid":"41322536","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11557","title":"Effectiveness of switching strategies in CGRP monoclonal antibody therapy for migraine: A retrospective cohort study.","authors":"Jaimes, Alex; Gómez, Andrea; Pajares, Olga; Rodríguez-Vico, Jaime","year":2025,"journal":"Headache, 65(4), 619-630","doi":"10.1111/head.14865","pmid":"39727075","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11558","title":"Retrospective cohort study of anti-CGRP monoclonal antibody unresponsive migraine individuals treated with atogepant: The RESCUE study.","authors":"Jaimes, Alex; Rodríguez-Vico, Jaime; Pajares, Olga; Eguilior Caffarena, Ignacio; Nystrom Hernández, Anna Lena; Gómez, Andrea; Porta-Etessam, Jesús","year":2025,"journal":"Cephalalgia : an international journal of headache, 45(6), 3331024251346925","doi":"10.1177/03331024251346925","pmid":"40501126","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Of 44 participants who had failed anti-CGRP monoclonal antibodies (88.6% chronic migraine), atogepant at 3 months produced:\n- 18.2% achieved ≥50% reduction in monthly headache days (MHDs)\n- 25.0% achieved ≥30% reduction in MHDs\n- 33.3% achieved ≥50% reduction in moderate-to-severe headache days (MSHDs)\n- Median MHDs decreased from 24.5 to 21.5 (p=0.011)\n- Median MSHDs decreased from 15.0 to 12.0 (p=0.001)\n- 59.1% reported some degree of improvement on Patient Global Impression scale\n- Acute medication days and HIT-6 disability scores also significantly decreased\n- Constipation occurred in 31.8%; 11.4% discontinued due to side effects","whyItMatters":"Patients who fail multiple anti-CGRP antibodies represent a challenging clinical population with few remaining preventive options. This study provides the first real-world evidence that switching from antibodies to atogepant — a small molecule gepant that blocks the same pathway but through a different mechanism — can still benefit a meaningful subset of these patients. This is important for clinical decision-making when antibody treatments fail.","specificNumbers":"","methodology":"This retrospective cohort study (RESCUE) screened 213 medical records and identified 44 patients with episodic or chronic migraine who discontinued anti-CGRP monoclonal antibodies (erenumab, galcanezumab, or fremanezumab) due to lack or loss of efficacy and subsequently started atogepant. Outcomes were assessed at 3 months including headache day frequency, severity, acute medication use, disability scores, patient-reported improvement, and adverse events.","limitations":"This is a retrospective study without a control group, making it impossible to account for placebo effects or natural disease fluctuation. The sample size of 44 is relatively small. Most patients (88.6%) had chronic migraine, limiting generalizability to episodic migraine. The 3-month follow-up is relatively short. Selection bias may exist in who was offered atogepant after antibody failure. The high constipation rate (31.8%) and 11.4% discontinuation rate are notable."},{"rthcId":"RPEP-11559","title":"Association Between Glucagon-Like Peptide-1 Receptor Agonists and Risk of Arrhythmias.","authors":"Jaiswal, Vikash; Hanif, Muhammad; Goyal, Aman; Yasmeen, Juveriya; Garimella, Vamsi; Mashkoor, Yusra; Vempati, Roopeessh; Deb, Novonil; Nasir, Yusra Minahil; Rajak, Kripa; Shrestha, Abhigan Babu; Mattumpuram, Jishanth; Weinberg, Andrew","year":2025,"journal":"Journal of arrhythmia, 41(6), e70242","doi":"10.1002/joa3.70242","pmid":"41404443","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11560","title":"Gepants: targeting the CGRP pathway for migraine relief.","authors":"Jakubowska, Bernadetta; Sowa-Kućma, Magdalena","year":2025,"journal":"Frontiers in pharmacology, 16, 1708226","doi":"10.3389/fphar.2025.1708226","pmid":"41357877","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11561","title":"Subchronic modulation of bitter taste receptors (TAS2R) by procyanidins. Unravelling the complex interplay between stimulation and expression.","authors":"Jalsevac, Florijan; Descamps-Solà, Maria; Vilalta, Adrià; Segú, Helena; Blay, M Teresa; Beltrán-Debón, Raúl; Rodríguez-Gallego, Esther; Terra, Ximena; Ardévol, Anna; Pinent, Montserrat","year":2025,"journal":"Journal of physiology and biochemistry, 81(4), 1321-1334","doi":"10.1007/s13105-025-01122-6","pmid":"40991204","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11562","title":"Unravelling the ties that bind: The intersection of obesity, osteoarthritis, and inflammatory pathways with emphasis on glucagon-like peptide-1 agonists.","authors":"Jamal, Naadir; Hollabaugh, William; Scott, Leon; Takkouche, Sahar","year":2025,"journal":"Clinical obesity, 15(1), e12700","doi":"10.1111/cob.12700","pmid":"39152660","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies shared inflammatory cascades between obesity and osteoarthritis, suggesting these are not merely co-occurring conditions but mechanistically linked through common inflammatory pathways. GLP-1 receptor agonists, which are peptide-based therapeutics, demonstrate anti-inflammatory properties beyond their metabolic effects, making them potential candidates for simultaneously addressing both obesity and osteoarthritis-related inflammation.","whyItMatters":"Obesity and osteoarthritis frequently co-occur and create a vicious cycle where excess weight increases joint stress while joint pain limits physical activity, promoting further weight gain. Finding a single therapy that addresses both conditions through their shared inflammatory biology could significantly improve quality of life for millions of patients dealing with this dual burden.","specificNumbers":"","methodology":"This is a narrative review that synthesizes existing literature on the inflammatory mechanisms connecting obesity and osteoarthritis, then evaluates the evidence for GLP-1 receptor agonists as a therapeutic intervention targeting these shared pathways.","limitations":"As a narrative review, this paper does not include original data or a systematic methodology for literature selection. The therapeutic potential of GLP-1 agonists for osteoarthritis is discussed based on mechanistic reasoning rather than direct clinical trial evidence in osteoarthritis patients. The conclusions are hypothesis-generating rather than definitive."},{"rthcId":"RPEP-11563","title":"Effect of once-weekly subcutaneous semaglutide on arterial inflammation in people with type 2 diabetes and cardiovascular disease using PET-MRI: Primary results of a randomized, double-blind, placebo-controlled trial.","authors":"James, Stefan; Christoffersen, Andreas Dyreborg; David, Jens-Peter; Hacker, Marcus; Jensen, Maria D Radu Juul; Mellbin, Linda; Pieber, Thomas R; Ripa, Rasmus Sejersten; Rossing, Peter; Svehlikova, Eva; Kjaer, Andreas","year":2025,"journal":"American heart journal, 289, 17-27","doi":"10.1016/j.ahj.2025.05.001","pmid":"40345413","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11564","title":"Impact of Semaglutide Administration on Weight Loss After Bariatric Surgery: A Meta-Analysis.","authors":"Jamialahamdi, Tannaz; Mirhadi, Elaheh; Almahmeed, Wael; Virani, Salim; Eid, Ali H; Al-Rasadi, Khalid; Salehabadi, Sepideh; Sahebkar, Amirhossein","year":2025,"journal":"Obesity surgery, 35(7), 2490-2497","doi":"10.1007/s11695-025-07848-y","pmid":"40418526","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11565","title":"Beyond fat: Does semaglutide affect lean mass?","authors":"Jamialahmadi, Tannaz; Eid, Ali H; Gadde, Kishore M; Almahmeed, Wael; Kroh, Matthew; Al Zein, Mohammad; Sahebkar, Amirhossein","year":2025,"journal":"Clinical nutrition (Edinburgh, Scotland), 44, 104-108","doi":"10.1016/j.clnu.2024.12.004","pmid":"39647240","tags":[],"studyType":"opinion-review","evidenceStrength":"preliminary","keyFinding":"The evidence on semaglutide's impact on lean mass (muscle) is contradictory. Some studies show that while semaglutide causes decreases in both lean mass and fat mass, the ratio of lean mass to total body mass actually improves — meaning fat is lost proportionally faster than muscle. However, larger clinical trials have found significant reductions in lean mass, raising concerns about muscle loss.\n\nThis contradiction makes the real-world impact unclear: semaglutide users are definitely losing some muscle along with fat, but whether this represents a clinically meaningful problem — or simply the normal lean mass loss that accompanies any significant weight reduction — remains debated.","whyItMatters":"With millions of people now taking semaglutide for weight loss, the question of whether they're losing dangerous amounts of muscle is urgent. Muscle loss can lead to weakness, falls (especially in older adults), metabolic slowdown, and the characteristic \"Ozempic face\" and \"Ozempic butt\" that have drawn media attention. Understanding the true impact on lean mass is essential for guiding exercise recommendations, protein intake, and patient selection for GLP-1 therapy.","specificNumbers":"Opinion paper synthesizing conflicting evidence · Lean-to-total body mass ratio may improve · Larger trials show significant lean mass reduction · No specific effect sizes reported","methodology":"This is an opinion paper published in Clinical Nutrition that synthesizes and interprets existing research on semaglutide's effects on body composition, specifically lean mass. It discusses findings from multiple investigations and clinical trials to frame the current state of the debate.","limitations":"As an opinion paper rather than a systematic review or meta-analysis, the evidence synthesis is selective rather than comprehensive. No specific effect sizes, percentages of lean mass loss, or trial-level data are reported in the abstract. The paper identifies the controversy but doesn't resolve it."},{"rthcId":"RPEP-11566","title":"Neuropsychiatric side effects of semaglutide in patients with dementia.","authors":"Jamshed, Namirah; Rehman, Syed Tabish; Khan, Noor","year":2025,"journal":"BMJ case reports, 18(8)","doi":"10.1136/bcr-2024-262743","pmid":"40759509","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11567","title":"Tcf4 regulates secretory cell fate decisions in the small intestine and colon tumors: insights from transcriptomic, histological, and microbiome analyses.","authors":"Janeckova, Lucie; Stastna, Monika; Hrckulak, Dusan; Berkova, Linda; Kubovciak, Jan; Onhajzer, Jakub; Kriz, Vitezslav; Dostalikova, Stela; Mullerova, Tereza; Vecerkova, Katerina; Tenglerova, Marketa; Coufal, Stepan; Kostovcikova, Klara; Blumberg, Richard S; Filipp, Dominik; Basler, Konrad; Valenta, Tomas; Kolar, Michal; Korinek, Vladimir","year":2025,"journal":"Stem cell research & therapy, 16(1), 170","doi":"10.1186/s13287-025-04280-y","pmid":"40221753","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Deleting Tcf4 in mouse intestinal cells produced several major findings:\n\n1. Paneth cells — the main producers of α-defensin antimicrobial peptides in the small intestine — were completely lost, and antimicrobial peptide expression was abolished.\n\n2. Loss of Tcf4 shifted secretory progenitor differentiation from Paneth cells toward goblet cells, revealing Tcf4 as the binary switch between these two cell fates.\n\n3. The gut microbiota was disrupted when Paneth cells and their defensins disappeared, demonstrating the critical role of these peptides in maintaining microbial balance.\n\n4. Alternative secretory progenitors compensated by producing Wnt ligands to maintain stem cell function and epithelial renewal even without Paneth cells.\n\n5. In colon adenomas, Paneth-like tumor cells that express defensins and Wnt3 ligands also require Tcf4 for their identity. Losing Tcf4 converts them to goblet cells, potentially disrupting tumor self-renewal.","whyItMatters":"Defensins are the gut's first line of antimicrobial defense, and their loss is associated with inflammatory bowel disease and increased infection susceptibility. Understanding that Tcf4 is the master regulator of defensin-producing Paneth cells could lead to therapies that boost defensin production in patients with weakened gut immunity. The surprising finding of defensin-producing cells in colon tumors also opens a new angle for cancer therapy — disrupting Tcf4 in tumors could undermine their ability to self-renew.","specificNumbers":"","methodology":"The researchers used conditional Tcf7l2 (Tcf4) gene deletion in mice with cell type-specific Cre recombinases and fluorescent reporter alleles to track cell fate. Analyses included single-cell and bulk RNA sequencing (transcriptomics), histological examination, microbiome profiling, antibiotic treatment experiments, and intestinal organoid cultures for functional validation. Both small intestinal and colon tumor tissues were analyzed.","limitations":"This is a mouse study, and while the Wnt/Tcf4 pathway is conserved in humans, there are known species differences in intestinal cell biology and defensin repertoires. The conditional knockout approach may not fully model subtle Tcf4 dysregulation seen in human disease. The colon tumor findings are from mouse adenomas, which may not fully represent human colorectal cancer biology. Therapeutic targeting of Tcf4 would need to balance potential benefits in cancer with the critical role of Tcf4 in normal gut defensin production."},{"rthcId":"RPEP-11568","title":"Improvement in global longitudinal strain following plasma cell-directed therapy is associated with long-term survival among patients with AL amyloidosis.","authors":"Jang, Kristine H; Yu, Anthony F; Landau, Heather; Ma, Xiaoyue; Cheng, Richard K; Mauer, Mathew S; Chuy, Katherine Lee; Lenihan, Daniel; Yang, Ji Can; Chen, Carol L; Liu, Jennifer E","year":2025,"journal":"European heart journal open, 5(5), oeaf104","doi":"10.1093/ehjopen/oeaf104","pmid":"40980714","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11569","title":"CPPpred-En: Ensemble framework integrating a protein language model and conventional features for highly accurate cell-penetrating peptide prediction.","authors":"Jang, Yong Eun; Kwon, Minjun; Kim, Seok Gi; George, Nimisha Pradeep; Hwang, Ji Su; Basith, Shaherin; Lee, Gwang","year":2025,"journal":"Computers in biology and medicine, 195, 110590","doi":"10.1016/j.compbiomed.2025.110590","pmid":"40543267","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CPPpred-En achieved state-of-the-art performance on two benchmark datasets:\n\n- CPP924 dataset: 97.27% accuracy, MCC = 0.964\n- MLCPP 2.0 dataset: 96.10% accuracy, MCC = 0.707\n- Outperformed all existing prediction tools on both datasets\n\nThe key innovation was combining:\n- Multiple protein language model (PLM) features (learned representations from large protein databases)\n- Conventional peptide features (physicochemical properties, amino acid composition)\n- Ensemble learning across multiple machine learning classifiers\n- High-performing feature-classifier combinations selected and integrated\n\nThe model showed strong generalization across different datasets, demonstrating robustness.","whyItMatters":"Cell-penetrating peptides are crucial for the next generation of drug delivery — enabling therapies like siRNA, CRISPR components, and large molecules to enter cells that they otherwise couldn't reach. A prediction tool with 97% accuracy could save years of laboratory screening, allowing researchers to computationally identify the most promising CPP candidates before synthesizing and testing them. This accelerates the entire peptide-based drug delivery pipeline.","specificNumbers":"","methodology":"The researchers evaluated multiple types of features: protein language model (PLM) embeddings from several pretrained models and conventional peptide features (amino acid composition, physicochemical properties, etc.). These were tested across various machine learning classifiers. High-performing feature-classifier combinations were selected and integrated through ensemble learning. The model was trained and validated on two established CPP benchmark datasets (CPP924 and MLCPP 2.0) and compared against existing state-of-the-art prediction tools.","limitations":"The model was validated computationally on existing datasets — no new experimental validation with synthesized peptides was performed. The MCC on the MLCPP 2.0 dataset (0.707) is notably lower than on CPP924 (0.964), suggesting variable performance across datasets. The model predicts binary CPP/non-CPP classification and may not capture nuances like cell-type specificity, uptake efficiency, or toxicity. Protein language models require significant computational resources. Performance on novel peptide classes not represented in training data is unknown."},{"rthcId":"RPEP-11570","title":"Cell-penetrating peptides as facilitators of cargo-specific nanocarrier-based drug delivery.","authors":"Jankowski, Ashleigh M; Ensign, Matthew A; Maisel, Katharina","year":2025,"journal":"Nanoscale, 17(35), 20006-20019","doi":"10.1039/d5nr00617a","pmid":"40856125","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11571","title":"Modulation of metabolic, inflammatory and fibrotic pathways by semaglutide in metabolic dysfunction-associated steatohepatitis.","authors":"Jara, Maximilian; Norlin, Jenny; Kjær, Mette Skalshøi; Almholt, Kasper; Bendtsen, Kristian M; Bugianesi, Elisabetta; Cusi, Kenneth; Galsgaard, Elisabeth D; Geybels, Milan; Gluud, Lise L; Harder, Lea M; Loomba, Rohit; Mazzoni, Gianluca; Newsome, Philip N; Nitze, Louise M; Palle, Mads S; Ratziu, Vlad; Sejling, Anne-Sophie; Wong, Vincent W-S; Anstee, Quentin M; Knudsen, Lotte B","year":2025,"journal":"Nature medicine, 31(9), 3128-3140","doi":"10.1038/s41591-025-03799-0","pmid":"40691365","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11572","title":"Assessing the Oncological Safety of Glucagon-Like Peptide-1 Receptor Agonists: A Systematic Review and Meta-Analysis.","authors":"Jaradat, Jaber H; Al-Ahmad, Rawan I; Al Jaghbeer, Maha; Abdelaziz, Ahlam A; Abu Afifeh, Nour M; Abu Afifeh, Ghazi; Rao, Asad; Alzoubi, Amjad; Nashwan, Abdulqadir J","year":2025,"journal":"Cureus, 17(11), e96071","doi":"10.7759/cureus.96071","pmid":"41356998","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11573","title":"Molecular Mechanisms and Antidiabetic Effects of Mango (Mangifera indica) Leaf Extract as a GLP-1 Analogue in Type 2 Diabetic Rats.","authors":"Jariyapongskul, Amporn; Boonsri, Pornthip; Sungwienwong, Itthipol; Dolsophon, Kulvadee; Apiratikul, Nuttapon; Jittangprasert, Piyada; Sitthisuk, Pornnapa; Rungsiwiwut, Ruttachuk; Samosorn, Siritron; Suksamrarn, Sunit; Watanapokasin, Ramida","year":2025,"journal":"International journal of molecular sciences, 26(24)","doi":"10.3390/ijms262412149","pmid":"41465578","tags":[],"studyType":"animal-and-cell","evidenceStrength":"preliminary","keyFinding":"Mango leaf extract (MLE) stimulated GLP-1 secretion from intestinal L-cells through two signaling pathways (MAPK and Wnt), and when given to diabetic rats at 40 mg/kg, it significantly reduced fasting blood glucose, body weight, cholesterol, triglycerides, and HbA1c. MLE also lowered DPP-IV levels (the enzyme that breaks down GLP-1), resulting in increased circulating GLP-1 comparable to the diabetes drug sitagliptin.\n\nThe active compound mangiferin was identified at 165.67 μg/g in the crude extract, and molecular docking confirmed its interaction with the relevant signaling proteins.","whyItMatters":"GLP-1-based drugs like semaglutide and sitagliptin are blockbuster treatments for diabetes and obesity, but they're expensive and require prescriptions. If a natural plant extract can stimulate the body's own GLP-1 production through the same pathways, it could offer an accessible supplement option — though this has only been shown in rats and cell cultures so far.","specificNumbers":"MLE dose: 40 mg/kg · Mangiferin: 165.67 ± 10.88 μg/g · Extract yield: 12.07% w/w · Reduced FBG, HbA1c, CHOL, TG · Lowered HOMA-IR · GLP-1 increase comparable to sitagliptin","methodology":"The study combined cell culture experiments (NCI-H716 intestinal L-cells to test GLP-1 secretion and signaling pathways), molecular docking (computer modeling of mangiferin's interactions with target proteins), and an in vivo study in type 2 diabetic Sprague-Dawley rats receiving MLE at 40 mg/kg orally. Metabolic parameters were measured including blood glucose, insulin, HbA1c, lipids, DPP-IV, and GLP-1.","limitations":"This is an animal and cell culture study — the results have not been tested in humans. The diabetic rat model may not fully replicate human type 2 diabetes. Specific sample sizes for the animal groups were not stated in the abstract. The long-term safety and efficacy of MLE at these doses is unknown, and bioavailability in humans could differ significantly."},{"rthcId":"RPEP-11574","title":"Cardiorenal Syndrome in the Elderly: Challenges and Considerations.","authors":"Jarocki, Matthew; Green, Sophie; Wu, Henry H L; Chinnadurai, Rajkumar","year":2025,"journal":"Geriatrics (Basel, Switzerland), 10(4)","doi":"10.3390/geriatrics10040104","pmid":"40863571","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11575","title":"Ingestion-activated CGRP neurons control learning but not satiety.","authors":"Jarvie, Brooke C; Ravi, Anagh; Nanavati, Rhea; Qiu, Longhui; Ly, Truong; Oh, Jun Y; Barnhill, Olivia K; Knight, Zachary A","year":2025,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2025.10.08.681275","pmid":"41278980","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11576","title":"Tirzepatide for Obesity Treatment and Diabetes Prevention.","authors":"Jastreboff, Ania M; le Roux, Carel W; Stefanski, Adam; Aronne, Louis J; Halpern, Bruno; Wharton, Sean; Wilding, John P H; Perreault, Leigh; Zhang, Shuyu; Battula, Ramakrishna; Bunck, Mathijs C; Ahmad, Nadia N; Jouravskaya, Irina","year":2025,"journal":"The New England journal of medicine, 392(10), 958-971","doi":"10.1056/NEJMoa2410819","pmid":"39536238","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Three years of once-weekly tirzepatide in people with obesity and prediabetes produced sustained weight loss of 12-20% (dose-dependent) versus 1.3% with placebo. Most remarkably, tirzepatide reduced progression to type 2 diabetes by 93% (1.3% vs 13.3%, HR 0.07, p<0.001). Even after 17 weeks off treatment, diabetes protection persisted (2.4% vs 13.7%, HR 0.12). The most common side effects were GI symptoms, mostly mild-moderate during dose escalation, with no new safety signals over 3 years.","whyItMatters":"This is the first major trial to demonstrate that a peptide drug can prevent type 2 diabetes while simultaneously treating obesity over 3 years. A 93% reduction in diabetes onset is among the largest preventive effects ever demonstrated for any medication, potentially reframing obesity treatment as diabetes prevention.","specificNumbers":"n=1,032 with obesity+prediabetes · 176 weeks treatment · weight loss: -12.3% (5mg), -18.7% (10mg), -19.7% (15mg) vs -1.3% placebo · diabetes onset: 1.3% vs 13.3% (HR 0.07) · 93% diabetes risk reduction · p<0.001 for all","methodology":"Phase 3, double-blind, randomized, placebo-controlled trial (SURMOUNT-1). 2,539 total participants randomized 1:1:1:1 to tirzepatide 5mg, 10mg, or 15mg weekly or placebo. This analysis focused on the 1,032 participants with obesity and prediabetes, treated for 176 weeks (3.4 years) followed by a 17-week off-treatment period. Key endpoints: percent weight change at 176 weeks and type 2 diabetes onset during treatment and off-treatment periods.","limitations":"Industry-funded (Eli Lilly). The analysis focused on the prediabetes subgroup (1,032 of 2,539 total participants). Weight regain and diabetes onset after long-term drug discontinuation beyond 17 weeks remain unknown. Cost and access barriers may limit real-world impact. GI side effects during dose escalation may affect tolerability."},{"rthcId":"RPEP-11577","title":"The Role of Substance P in Corneal Homeostasis.","authors":"Jastrzębska-Miazga, Irmina; Machna, Bartosz; Wyględowska-Promieńska, Dorota; Smędowski, Adrian","year":2025,"journal":"Biomolecules, 15(5)","doi":"10.3390/biom15050729","pmid":"40427622","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11578","title":"Semaglutide-Induced Small Bowel Pseudo-Obstruction and Ileitis in a Patient With Type 2 Diabetes: A Case Report.","authors":"Javed, Faiza; Shaat, Iman A A; Oyibo, Samson O","year":2025,"journal":"Cureus, 17(7), e88350","doi":"10.7759/cureus.88350","pmid":"40687404","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11579","title":"Analytical Validation of a Novel Point-Of-Care Quantitative Immunoassay for Feline N-Terminal Pro-Brain Natriuretic Peptide.","authors":"Javery, Emily A; Fries, Ryan C; Kadotani, Saki; Kruckman, Leah; Humphries, Lindsey; Prabhakar, Sumana R; Rosser, Michael F","year":2025,"journal":"Veterinary clinical pathology, 54(4), 369-376","doi":"10.1111/vcp.70062","pmid":"41186151","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11580","title":"Differential Gastric Motility, Gut Hormone, and Appetite Changes Following A Mixed Meal in People With Obesity and Healthy Controls.","authors":"Javidi, Darius; Webb, Dominic-Luc; Diaz, Hetzel Olenia; Ud-Din, Moeen; Elias, Khalid; Sundbom, Magnus; Hellström, Per M","year":2025,"journal":"Neurogastroenterology and motility, 37(11), e70163","doi":"10.1111/nmo.70163","pmid":"40961390","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11581","title":"Integrating Pharmacogenomic Insights in GLP-1 Receptor Agonist Therapy: Direct GLP1R and ARRB1 Variants and Indirect CYP2D6 Influences in Personalized Obesity Management.","authors":"Jayathilaka, Navodi Sandamini; Weththasinghe, Arunodya Vishwanthi; Ganamurali, Nila; Sabarathinam, Sarvesh","year":2025,"journal":"Clinical pharmacology in drug development","doi":"10.1002/cpdd.1624","pmid":"41238444","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11582","title":"YN1548: A novel small-molecule agonist of human glucagon-like peptide-1 receptor for the treatment of type 2 diabetes mellitus and obesity.","authors":"Je, In-Gyu; Kim, Tae-Kwang; Lee, Hyeong Jun; Lee, Mi-Young; An, Kyung-Mi; Park, Joon-Tae; Kim, Ki-Young","year":2025,"journal":"European journal of pharmacology, 1006, 178143","doi":"10.1016/j.ejphar.2025.178143","pmid":"40945896","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11583","title":"GLP-1 Receptor Agonist Medications for Obesity and Type 2 Diabetes Treatment: A Rapid Review of Changes in Eating Behaviors and Eating Disorder Risk.","authors":"Jebeile, Hiba; Danielsen, Yngvild Sørebø; Sumithran, Priya; Lorien, Sasha; Jardine, Isabelle R; Baur, Louise A; Lister, Natalie B","year":2025,"journal":"Obesity reviews : an official journal of the International Association for the Study of Obesity, e70049","doi":"10.1111/obr.70049","pmid":"41340366","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11584","title":"Efficacy of 12 months therapy with glucagon-like peptide-1 receptor agonists liraglutide and semaglutide on weight regain after bariatric surgery: a real-world retrospective observational study.","authors":"Jensen, Anders Boisen; Machado, Ursina; Renström, Frida; Aczél, Stefan; Folie, Patrick; Biraima-Steinemann, Magdalena; Bilz, Stefan","year":2025,"journal":"BMC endocrine disorders, 25(1), 93","doi":"10.1186/s12902-025-01913-4","pmid":"40197361","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11585","title":"Blood phosphatidylethanol measurements indicate GLP-1 receptor stimulation causes delayed decreases in alcohol consumption.","authors":"Jensen, Mathias E; Klausen, Mette K; Bergmann, Marianne L; Knudsen, Gitte M; Vilsbøll, Tina; Stove, Christophe; Fink-Jensen, Anders","year":2025,"journal":"Alcohol, clinical & experimental research, 49(5), 1161-1165","doi":"10.1111/acer.70041","pmid":"40123107","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11586","title":"Glucagon-like peptide-1 receptor modulates cerebrospinal fluid secretion and intracranial pressure in rats.","authors":"Jensen, Mette N; Israelsen, Ida M E; Wardman, Jonathan H; Jensen, Dennis B; Andersen, Daniel B; Toft-Bertelsen, Trine L; Rath, Martin F; Holst, Jens Juul; Rosenkilde, Mette M; MacAulay, Nanna","year":2025,"journal":"Fluids and barriers of the CNS, 22(1), 41","doi":"10.1186/s12987-025-00652-x","pmid":"40275284","tags":["glp-1"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"GLP-1 receptors on the choroid plexus (the brain structure that produces cerebrospinal fluid) directly modulate CSF production and intracranial pressure in rats. When researchers activated GLP-1 receptors centrally (directly in the brain), CSF secretion increased and intracranial pressure rose. When they blocked GLP-1 receptors, CSF secretion decreased. Crucially, these effects only occurred with central (brain) administration — not peripheral (body) injection — indicating the relevant receptors are on the CSF-facing side of the choroid plexus.\n\nGLP-1R expression was confirmed in the choroid plexus at both mRNA and protein levels, and the receptor modulated transporter activity in the choroid plexus tissue.","whyItMatters":"This is a mechanistically important study for two reasons: (1) It provides a potential explanation for how GLP-1 drugs might help conditions like idiopathic intracranial hypertension — by modulating CSF production through choroid plexus GLP-1 receptors. (2) It reveals that GLP-1 signaling in the brain directly affects a fundamental physiological process (CSF dynamics) that, if dysregulated, can be fatal. This opens a new pharmacological target for conditions with elevated intracranial pressure.","specificNumbers":"GLP-1R agonist: exendin-4 · GLP-1R antagonist: exendin-9-39 · Central (i.c.v.) administration effective · Peripheral (i.p.) not effective · GLP-1R confirmed in choroid plexus (mRNA + protein) · CSF secretion rate modulated bidirectionally","methodology":"Male rats received either a GLP-1R agonist (exendin-4) or antagonist (exendin-9-39) via intraperitoneal or intracerebroventricular injection. CSF secretion rate and intracranial pressure were measured in vivo. GLP-1R expression in the choroid plexus was confirmed using RNAScope in situ hybridization and western blotting. Transporter activity was assessed using radio-isotope flux assays in excised choroid plexus tissue.","limitations":"Rat study — the choroid plexus GLP-1R expression and CSF dynamics may differ in humans. The central (i.c.v.) administration route used in the key experiments delivers drugs directly to the brain, which is very different from how GLP-1 drugs are taken clinically (subcutaneous injection). Whether peripherally administered GLP-1 drugs reach brain GLP-1 receptors at sufficient concentrations to affect CSF production in humans is unknown. GLP-1R expression in the choroid plexus was described as 'low level.'"},{"rthcId":"RPEP-11587","title":"Beyond the prescription: Global observations on the social implications of GLP-1 receptor agonists for weight loss.","authors":"Jensen, Sissel Due; Gualano, Bruno; Andreassen, Pernille; Scagliusi, Fernanda Baeza; SturtzSreetharan, Cindi; Brewis, Alexandra","year":2025,"journal":"PLOS global public health, 5(12), e0005516","doi":"10.1371/journal.pgph.0005516","pmid":"41452858","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11588","title":"Semaglutide and Taste in Women With Obesity and Polycystic Ovary Syndrome: A Randomized Placebo-Controlled Study.","authors":"Jensterle, Mojca; Kovac, Jernej; Vovk, Andrej; Ferjan, Simona; Battelino, Saba; Battelino, Tadej; Janez, Andrej","year":2025,"journal":"The Journal of clinical endocrinology and metabolism, 111(1), e270-e280","doi":"10.1210/clinem/dgaf278","pmid":"40341357","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11589","title":"Variant angina associated with a CGRP receptor antagonist: a case report.","authors":"Jeon, Hongki; Cho, Jin-Man","year":2025,"journal":"BMC neurology, 25(1), 231","doi":"10.1186/s12883-025-04260-y","pmid":"40442685","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11590","title":"Genetically proxied glucagon-like peptide-1 receptor perturbation and risk of mood disorders: a Mendelian randomization study.","authors":"Jeon, Yaejin; Kim, Ju Han","year":2025,"journal":"BMC psychiatry, 25(1), 768","doi":"10.1186/s12888-025-07152-0","pmid":"40770700","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11591","title":"Improved Intestinal Permeation of Cyclosporin a by FCIGRL-Modified Tight Junction Modulator in Rats.","authors":"Jeong, Dong-Ho; Kim, Jung-Woo; Song, Keon-Hyoung","year":2025,"journal":"Pharmaceutics, 17(11)","doi":"10.3390/pharmaceutics17111395","pmid":"41304733","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11592","title":"Periodontitis and GLP-1 pathways: a new frontier in oral-systemic health connections -a scoping review.","authors":"Jeong, Natalie; Chuang, Lin-Hsin; Ho, Yolanda","year":2025,"journal":"Frontiers in clinical diabetes and healthcare, 6, 1679511","doi":"10.3389/fcdhc.2025.1679511","pmid":"41307071","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 52 studies (1990–2025), the review identified several key findings: (1) Periodontitis may impair GLP-1 signaling and worsen glucotoxicity and lipotoxicity in diabetes/obesity. (2) Periodontopathic bacteria, notably P. gingivalis, produce DPP-4-like enzymes that degrade GLP-1 and potentially disrupt glucose regulation. (3) GLP-1 RAs (liraglutide, exendin-4) demonstrated anti-inflammatory, osteoprotective, and regenerative effects in preclinical periodontal models. (4) Host and microbial DPP-4 activity serves as a key mechanistic link between periodontal inflammation and systemic insulin resistance.","whyItMatters":"About half of adults have some form of gum disease, and the connection between oral health and diabetes is well-established but poorly understood mechanistically. The discovery that oral bacteria can directly degrade GLP-1 provides a concrete molecular link. For the hundreds of millions taking GLP-1 drugs for diabetes, knowing these drugs may also protect their gums adds value, while understanding that gum disease may undermine their effectiveness highlights the importance of oral health.","specificNumbers":"","methodology":"Scoping review with systematic search of PubMed, Embase, and Cochrane Library for studies published between 1990 and 2025. Fifty-two studies were included, spanning in vitro, animal, and human clinical/observational research examining the relationship between periodontitis and GLP-1 pathways.","limitations":"This is a scoping review, which maps the available evidence but doesn't formally assess study quality or pool results. Most GLP-1 periodontal data come from preclinical models rather than human clinical trials. The microbial DPP-4 hypothesis is mechanistically compelling but not yet clinically validated. The heterogeneity of included studies (in vitro to clinical) limits direct comparisons."},{"rthcId":"RPEP-11593","title":"GLP-1 Receptor Agonists: Promising Therapeutic Targets for Alcohol Use Disorder.","authors":"Jerlhag, Elisabet","year":2025,"journal":"Endocrinology, 166(4)","doi":"10.1210/endocr/bqaf028","pmid":"39980336","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11594","title":"The Connection Between the Appetite-Regulatory Peptides Ghrelin and GLP-1 and Alcohol Use Disorder.","authors":"Jerlhag, Elisabet","year":2025,"journal":"Advances in experimental medicine and biology, 1477, 229-241","doi":"10.1007/978-3-031-89525-8_8","pmid":"40442388","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11595","title":"Semaglutide impacts skeletal muscle to a similar extent as caloric restriction in mice with diet-induced obesity.","authors":"Jeromson, S; Baranowski, B; Akcan, M; Waters, B D; Eisner, K; Bellucci, A; Trang, S; Abolhassani, A; Tello-Palencia, M A; Schweitzer, A; Stefanska, B; Mitchell, C J; Wright, David C","year":2025,"journal":"The Journal of physiology","doi":"10.1113/JP289449","pmid":"40982727","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide produced greater total weight loss than caloric restriction alone, even when calorie intake was matched between groups. Both treatments reduced muscle mass and strength to a similar extent, indicating that semaglutide's effect on muscle is primarily driven by reduced energy intake rather than a direct drug effect on muscle tissue.\n\nImportantly, transcriptomic analyses of skeletal muscle revealed distinct molecular responses between semaglutide-treated and calorie-restricted mice, suggesting the drug does have unique effects at the gene expression level despite similar functional outcomes.\n\nAfter discontinuation, both lean mass and fat mass rebounded to baseline levels within six weeks, and muscle size and strength were comparable across all groups at the end of the withdrawal period.","whyItMatters":"A major concern with GLP-1 drugs like semaglutide is that patients lose muscle along with fat, potentially harming metabolic health and physical function. This study provides reassuring evidence that semaglutide's muscle impact is no worse than what happens with ordinary dieting, and that muscle recovers after stopping treatment. However, the rebound in both fat and lean mass after discontinuation also underscores the challenge of maintaining weight loss without ongoing treatment.","specificNumbers":"","methodology":"Mice were first made obese through a high-fat diet, then divided into groups receiving either semaglutide injections or a calorie-matched restricted diet for four weeks. Researchers measured body weight, body composition (lean and fat mass), energy expenditure, muscle size, grip strength, and performed gene expression analysis (transcriptomics) on skeletal muscle. In a follow-up experiment, treatments were stopped after four weeks and the mice were monitored for six additional weeks to track weight and body composition rebound.","limitations":"This study was conducted in mice, and results may not directly translate to humans. The four-week treatment period is relatively short. Calorie matching was done at the group level, which may not perfectly replicate individual variation. The study did not assess long-term outcomes beyond the six-week withdrawal period, and did not test whether exercise or protein supplementation could mitigate muscle loss."},{"rthcId":"RPEP-11596","title":"Valorisation of fish scales and bones: a sustainable source of bioactive proteins and collagen for nutraceuticals.","authors":"Jeyachandran, Sivakamavalli; Aman, Mohammed","year":2025,"journal":"Bioresources and bioprocessing, 12(1), 141","doi":"10.1186/s40643-025-00970-w","pmid":"41335283","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Fish scales and bones contain 30-40% organic collagen matrix and 60-70% hydroxyapatite. Modern extraction methods achieve collagen yields of 25-35%, with ultrasound and microwave-assisted techniques reducing processing from days to minutes while preserving bioactivity.\n\nKey health findings include: antioxidant capacities comparable to or exceeding vitamins C and E; ACE-inhibitory peptides lowering blood pressure in preclinical models; and clinical trial evidence that 10 g daily fish collagen peptide supplementation for 8-12 weeks improves skin hydration, elasticity, wrinkle reduction, and reduces osteoarthritis-related joint pain. Nanocarrier delivery systems (nanoliposomes, nanoemulsions) enhance bioavailability and stability.","whyItMatters":"The seafood industry generates enormous amounts of fish waste. Converting this waste into health-promoting collagen peptides creates a sustainable, circular economy while providing consumers with clinically validated supplements for skin aging and joint health. This approach addresses both environmental waste and human health needs simultaneously.","specificNumbers":"","methodology":"This is a comprehensive review synthesizing evidence from extraction science, preclinical studies, and clinical trials on collagen and bioactive peptides derived from fish scales and bones. It covers extraction methods, peptide bioactivities, delivery technologies, and sustainability considerations.","limitations":"As a review, this paper synthesizes existing evidence rather than generating new data. While clinical trial results for skin and joint benefits are cited, the specific trial details (sample sizes, controls) are not elaborated. ACE-inhibitory effects remain preclinical. Standardization of peptide products across different fish species and extraction methods remains a challenge. Regulatory frameworks vary by country."},{"rthcId":"RPEP-11597","title":"Efficacy and safety of oral semaglutide in Chinese participants with type 2 diabetes: Subgroup analyses by baseline characteristics in the PIONEER 11 and 12 randomised controlled trials.","authors":"Ji, Linong; Yuan, Guoyue; Liu, Jun; Zhang, Bingjie; Liu, Wenyan; Shen, Zewei","year":2025,"journal":"Diabetes, obesity & metabolism, 27(11), 6386-6394","doi":"10.1111/dom.70031","pmid":"40843773","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11598","title":"Efficacy and safety of a biased GLP-1 receptor agonist ecnoglutide in adults with overweight or obesity: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.","authors":"Ji, Linong; Gao, Leili; Xue, Haibo; Tian, Junhang; Wang, Kun; Jiang, Hongwei; Huang, Chongbing; Lian, Qiufang; Yuan, Mingxia; Gao, Ge; Lu, Yibing; Han, Jie; Fu, Wenyan; Wang, Haifang; Zhang, Yawei; Shi, Xiaoguang; Wen, Binhong; Shi, Bimin; Hu, Wen; Guo, Tonglan; Xing, Ying; Li, Ya; Li, Qingju; Zheng, Qing; Yang, Ming; Ning, Jing; Guo, Mengying; Li, Yao; Pan, Hai","year":2025,"journal":"The lancet. Diabetes & endocrinology, 13(9), 777-789","doi":"10.1016/S2213-8587(25)00141-X","pmid":"40555243","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11599","title":"Once-Weekly Mazdutide in Chinese Adults with Obesity or Overweight.","authors":"Ji, Linong; Jiang, Hongwei; Bi, Yan; Li, Hua; Tian, Junhang; Liu, Dexue; Zhao, Yuzhu; Qiu, Wei; Huang, Chongbing; Chen, Lei; Zhong, Shao; Han, Jie; Zhang, Yawei; Lian, Qiufang; Yang, Ping; Lv, Lingchun; Gu, Jieyu; Liu, Zihan; Deng, Huan; Wang, Yanqi; Li, Li; Pei, Lijuan; Qian, Lei","year":2025,"journal":"The New England journal of medicine, 392(22), 2215-2225","doi":"10.1056/NEJMoa2411528","pmid":"40421736","tags":["glp-1-agonists"],"studyType":"rct","evidenceStrength":"strong","keyFinding":"In this phase 3 NEJM-published trial (GLORY-1), mazdutide — a GLP-1/glucagon dual agonist — produced significant weight loss in 610 Chinese adults with obesity or overweight over 48 weeks. The 6 mg dose achieved 14.01% body weight reduction at week 48 (vs. 0.30% for placebo), and the 4 mg dose achieved 11.00%. At week 48, 49.5% of participants on the 6 mg dose lost ≥15% of their body weight. Both doses improved all prespecified cardiometabolic measures. Discontinuation rates due to adverse events were remarkably low (0.5-1.5%), with GI side effects being mostly mild to moderate.","whyItMatters":"Mazdutide is China's homegrown competitor to tirzepatide and semaglutide, and this NEJM publication validates it as a serious contender. Its dual GLP-1/glucagon mechanism differs from tirzepatide's GLP-1/GIP approach, potentially offering distinct metabolic benefits. The very low discontinuation rate is particularly notable for a weight loss drug.","specificNumbers":"n=610 · 48 weeks · 6 mg: -14.01% weight · 4 mg: -11.00% weight · Placebo: +0.30% · ≥5% loss: 82% (6 mg) · ≥15% loss: 49.5% (6 mg) · Discontinuation: 0.5-1.5% · p<0.001 all comparisons","methodology":"Phase 3, double-blind, placebo-controlled, randomized trial (GLORY-1) conducted in China. 610 adults aged 18-75 with BMI ≥28 (or ≥24 with comorbidities) were randomized 1:1:1 to mazdutide 4 mg, mazdutide 6 mg, or placebo for 48 weeks. Co-primary endpoints were percentage body weight change and proportion achieving ≥5% weight loss at week 32 using treatment-policy estimand analysis.","limitations":"Conducted exclusively in Chinese adults, so results may not generalize to other populations with different BMI distributions and metabolic profiles. Chinese BMI thresholds for obesity (≥28) and overweight (≥24) are lower than Western standards. No active comparator arm (e.g., semaglutide or tirzepatide), so direct comparison with existing drugs requires cross-trial interpretation. 48 weeks is meaningful but not long-term safety data."},{"rthcId":"RPEP-11600","title":"Cell-Penetrating Peptide-Mediated Delivery of Gene-Silencing Nucleic Acids to the Invasive Common Reed Phragmites australis via Foliar Application.","authors":"Ji, Qing; Kowalski, Kurt P; Golenberg, Edward M; Chung, Seung Ho; Barker, Natalie D; Bickford, Wesley A; Gong, Ping","year":2025,"journal":"Plants (Basel, Switzerland), 14(3)","doi":"10.3390/plants14030458","pmid":"39943020","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11601","title":"Improved Drug Adherence Improves Cardiac Outcomes after Myocardial Infarction in Diabetic Patients.","authors":"Ji, Wenna; Xue, Liang; Wang, Haijun; Liu, Xiaoni; Li, Taotao","year":2025,"journal":"Kardiologiia, 65(9), 61-71","doi":"10.18087/cardio.2025.9.n2937","pmid":"41129252","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11602","title":"Effect and Safety of Xinfuli Granules in Chronic Heart Failure with Qi Deficiency and Blood Stasis: A Single-Center Randomized Controlled Trial.","authors":"Ji, Xiao-di; Yan, Si-Yu; Lu, Pei-Pei; Ma, Li-Hong","year":2025,"journal":"Chinese journal of integrative medicine","doi":"10.1007/s11655-025-4022-7","pmid":"41129050","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11603","title":"Efficacy and safety of GLP-1 receptor agonists in the treatment of obese patients with chronic heart failure: a meta-analysis.","authors":"Jia, Anna; Yang, Ming; Wang, Tianhong; Hua, Yusi; Lu, Huimin","year":2025,"journal":"Frontiers in cardiovascular medicine, 12, 1633114","doi":"10.3389/fcvm.2025.1633114","pmid":"41112222","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11604","title":"Polyethylene glycol loxenatide reduces NETosis and immunofluorescence hyperactivation in Behçet's disease.","authors":"Jia, Fang; Wu, Xiaoli; Sheng, Huiyang","year":2025,"journal":"European journal of medical research, 30(1), 1187","doi":"10.1186/s40001-025-03442-1","pmid":"41299760","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11605","title":"Enhanced lymphatic transportation of SLN by mimicking oligopeptide transportation route.","authors":"Jia, Fuya; Fan, Xiaoxing; Wu, Licheng; Wang, Yating; Zhang, Jisen; Zhou, Zhou; Li, Lian; Wen, Jingyuan; Huang, Yuan","year":2025,"journal":"Asian journal of pharmaceutical sciences, 20(3), 101019","doi":"10.1016/j.ajps.2025.101019","pmid":"40503058","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11606","title":"Analysis of the long-term impact of glucagon-like peptide-1 (GLP-1) receptor agonists for control of obesity and obesity-related comorbidities: a meta-analysis.","authors":"Jia, Iwanger-I-Ter T; Bloomfield, Grace C; Chen, Mike Y; Cunningham, Marcus H; Azagury, Dan E; Alimi, Yewande R; Prindeze, Nicholas J","year":2025,"journal":"Surgical endoscopy, 39(12), 8580-8589","doi":"10.1007/s00464-025-12086-5","pmid":"41028671","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11607","title":"Silk fibroin hollow microneedle system for sustained transdermal administration of liraglutide: development and characterization.","authors":"Jia, Tianshuo; Geng, Yiyu; Shao, Huiyan; Tan, Guohongfang; Zhang, Xiaofeng; Kundu, Subhas C; Lu, Shenzhou","year":2025,"journal":"International journal of biological macromolecules, 322(Pt 2), 146884","doi":"10.1016/j.ijbiomac.2025.146884","pmid":"40816406","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11608","title":"Effects of intravesical cocktail instillation on outcomes and serum pain factors of patients with bladder pain syndrome.","authors":"Jia, Yunpeng; Zhang, Yuanning; Wang, Bo; Shi, Junjia","year":2025,"journal":"Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia","doi":"10.5507/bp.2025.029","pmid":"41222218","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11609","title":"Renoprotective effects of dulaglutide, a GLP-1 agonist, involving regulation of epithelial-mesenchymal transition in patients with type 2 diabetes and diabetic kidney disease.","authors":"Jiang, Daoli; Meng, Fandong; Chou, Xiaohua; Shen, Jiaxin; Liu, Miaoyan","year":2025,"journal":"International journal of clinical pharmacology and therapeutics, 63(4), 141-153","doi":"10.5414/CP204632","pmid":"39790030","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11610","title":"Pulmonary artery pressure trajectories in heart failure patients treated with GLP-1 receptor agonists.","authors":"Jiang, Haoran; Wattanachayakul, Phuuwadith; Kittipibul, Veraprapas; Nicolsen, Erika; McVeigh, Todd; Kamneva, Oksana; Fudim, Marat","year":2025,"journal":"ESC heart failure, 12(4), 2578-2582","doi":"10.1002/ehf2.15308","pmid":"40289068","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In nine heart failure patients with CardioMEMS implants treated with GLP-1 receptor agonists for 6 months, body weight decreased from 123.6 to 117.2 kg (p=0.047). Systolic pulmonary artery pressure fell from 38.9 to 34.0 mmHg (p=0.045), diastolic from 20.0 to 17.8 mmHg (p=0.019), and mean from 27.3 to 24.3 mmHg (p=0.018).\n\nWeight loss correlated significantly with reductions in systolic PAP (r=0.69, p=0.04) and mean PAP (r=0.72, p=0.029). Importantly, guideline-directed medical therapy and loop diuretic doses remained unchanged throughout, suggesting the hemodynamic improvements were attributable to GLP-1 RA treatment rather than changes in background therapy.","whyItMatters":"Elevated pulmonary artery pressure is a hallmark of worsening heart failure and predicts hospitalizations and death. This is among the first studies to use continuous invasive hemodynamic monitoring to show that GLP-1 drugs improve this key metric. If confirmed in larger trials, this could establish GLP-1 receptor agonists as a hemodynamic therapy for heart failure, beyond their known cardiovascular benefits.","specificNumbers":"","methodology":"This was a single-center retrospective cohort study of heart failure patients who had CardioMEMS pulmonary artery pressure monitors implanted and subsequently started semaglutide or tirzepatide for at least 6 months. Patients already on GLP-1 RAs before device implantation were excluded. Pulmonary artery pressures were continuously monitored, and correlations between weight change and pressure changes were assessed using Pearson correlation.","limitations":"This is a very small retrospective study with only nine patients and no control group. The association between weight loss and pressure reduction could be confounded by other factors. The median semaglutide dose (0.9 mg) was relatively low. Only 6 months of follow-up was available, and it's unclear if benefits persist or continue to improve with longer treatment. The single-center design limits generalizability."},{"rthcId":"RPEP-11611","title":"Cyclic cell-penetrating peptide-engineered ceria nanoparticles for non-invasive alleviation of ultraviolet radiation-induced cataract.","authors":"Jiang, Luyang; Liu, Jinxia; Chen, Silong; Cui, Wenyu; Guo, Jiarui; Cheng, Xiaoyu; Zheng, Yingying; Yang, Wenxin; Pan, Zicai; Wang, Yao; Zhao, Mary; Han, Haijie; Yao, Ke; Yu, Yibo","year":2025,"journal":"Journal of nanobiotechnology, 23(1), 337","doi":"10.1186/s12951-025-03402-1","pmid":"40336002","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11612","title":"Impact of metoprolol combined with spironolactone on cardiac function in patients with coronary heart disease complicated by heart failure.","authors":"Jiang, Mingfang; Wang, Niandong","year":2025,"journal":"American journal of translational research, 17(1), 664-673","doi":"10.62347/WWQN9188","pmid":"39959198","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11613","title":"Comparative efficacy and safety of different SGLT2 inhibitor-based combination strategies in HFrEF: a systematic review and network meta-analysis.","authors":"Jiang, Neng; Zhang, Yuling; Tang, Yue; Tan, Hongmei","year":2025,"journal":"Frontiers in endocrinology, 16, 1742128","doi":"10.3389/fendo.2025.1742128","pmid":"41550872","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11614","title":"Repeated Withdrawal of a GLPR Agonist Induces Hyperleptinemia and Deteriorates Metabolic Health in Obese Aging UM-HET3 Mice.","authors":"Jiang, Nisi; Yin, Jiyuan; Lawrence, Noah; Meng, Jieyi; Maeyens, Laurence T; Xu, Ziying; Li, Xin; Ekane, Mbolle; Chaudhary, Ariana; Cao, Pengju; Li, Guannan; Solis-Herrera, Carolina; Zhu, Yi; Zhao, Shangang","year":2025,"journal":"Aging cell, 24(10), e70210","doi":"10.1111/acel.70210","pmid":"40960340","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Aged obese UM-HET3 mice subjected to three cycles of liraglutide treatment followed by withdrawal (ON/OFF group) developed hyperleptinemia and visceral fat expansion, resulting in impaired metabolic health compared to both untreated controls and continuously treated mice.\n\nImportantly, while the ON/OFF mice regained fat mass after each treatment cycle, they consistently failed to restore lean mass. This unfavorable shift in body composition — losing muscle but regaining fat — suggests that intermittent GLP-1 therapy may increase vulnerability to sarcopenia, the age-related loss of muscle mass and function.","whyItMatters":"GLP-1 receptor agonists like liraglutide and semaglutide are among the most prescribed weight-loss drugs today. Many patients stop and restart these medications due to cost, side effects, or supply issues. This study provides the first evidence in aged animals that this yo-yo pattern may not simply return you to baseline — it could actively worsen metabolic health by driving up leptin, expanding visceral fat, and eroding muscle mass, which is especially dangerous in older adults already at risk for sarcopenia.","specificNumbers":"","methodology":"Aged obese UM-HET3 mice (a genetically diverse mouse strain) were divided into three groups: one receiving no liraglutide (OFF), one undergoing three cycles of treatment followed by withdrawal (ON/OFF), and one on continuous liraglutide treatment (ON). Researchers tracked body weight, food intake, body composition (fat vs. lean mass), leptin levels, and metabolic health markers across the treatment cycles.","limitations":"This was conducted in mice, not humans, so the findings may not directly translate to human patients. The UM-HET3 strain, while genetically diverse, does not fully replicate human metabolic complexity. The study did not report specific numerical values for leptin levels, body weight changes, or lean mass loss in the abstract. Long-term survival outcomes were not assessed."},{"rthcId":"RPEP-11615","title":"HIF regulates multiple translated endogenous retroviruses: Implications for cancer immunotherapy.","authors":"Jiang, Qinqin; Braun, David A; Clauser, Karl R; Ramesh, Vijyendra; Shirole, Nitin H; Duke-Cohan, Joseph E; Nabilsi, Nancy; Kramer, Nicholas J; Forman, Cleo; Lippincott, Isabelle E; Klaeger, Susan; Phulphagar, Kshiti M; Chea, Vipheaviny; Kim, Nawoo; Vanasse, Allison P; Saad, Eddy; Parsons, Teagan; Carr-Reynolds, Melissa; Carulli, Isabel; Pinjusic, Katarina; Jiang, Yijia; Li, Rong; Syamala, Sudeepa; Rachimi, Suzanna; Verzani, Eva K; Stevens, Jonathan D; Lane, William J; Camp, Sabrina Y; Meli, Kevin; Pappalardi, Melissa B; Herbert, Zachary T; Qiu, Xintao; Cejas, Paloma; Long, Henry W; Shukla, Sachet A; Van Allen, Eliezer M; Choueiri, Toni K; Churchman, L Stirling; Abelin, Jennifer G; Gurer, Cagan; MacBeath, Gavin; Childs, Richard W; Carr, Steven A; Keskin, Derin B; Wu, Catherine J; Kaelin, William G","year":2025,"journal":"Cell, 188(7), 1807-1827.e34","doi":"10.1016/j.cell.2025.01.046","pmid":"40023154","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11616","title":"Machine learning application to predict binding affinity between peptide containing non-canonical amino acids and HLA-A0201.","authors":"Jiang, Shan; Su, Zhaoqian; Bloodworth, Nathaniel; Liu, Yunchao; Martina, Cristina E; Harrison, David G; Meiler, Jens","year":2025,"journal":"PloS one, 20(6), e0314833","doi":"10.1371/journal.pone.0314833","pmid":"40577315","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11617","title":"Effect of liraglutide treatment on mitigation of hearing damage induced by multiday repeated high-intensity blasts.","authors":"Jiang, Shangyuan; Cai, Qunfeng; Jiang, Yijie; Gan, Rong Z","year":2025,"journal":"The Journal of the Acoustical Society of America, 158(2), 1431-1442","doi":"10.1121/10.0039047","pmid":"40853101","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11618","title":"Effects of Liraglutide on Mitigation of Hearing Loss After Repeated Blast Exposures: A Summary of Studies in Animal Model of Chinchilla.","authors":"Jiang, Shangyuan; Cai, Qunfeng; Bien, Alexander G; Gan, Rong Z; Jiang, Yijie","year":2025,"journal":"Military medicine, 190(Supplement_2), 512-520","doi":"10.1093/milmed/usaf255","pmid":"40984095","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Liraglutide treatment reduced blast-induced permanent hearing loss and facilitated hearing restoration as measured by auditory brainstem response (ABR). The effects varied by condition: in earplug-protected ears, pre-blast liraglutide reduced acute damage severity; in open ears, liraglutide facilitated post-injury hearing restoration.\n\nWave I suprathreshold amplitude analysis showed pre-injury treatment mitigated blast-induced temporary damage to the peripheral auditory system. Histopathological examination confirmed that liraglutide protected cochlear hair cells against blast injury. Higher-intensity blasts (15-25 psi) caused more severe and permanent damage than lower-intensity blasts (3-5 psi). Optimal protective effects were achieved when liraglutide was administered before injury.","whyItMatters":"Hearing loss and tinnitus are the most common service-related disabilities among military personnel, affecting hundreds of thousands of veterans. No drug currently prevents or treats blast-induced hearing loss. Liraglutide is already FDA-approved with a known safety profile, which could accelerate clinical translation. A pre-deployment injection that protects hearing could transform military medicine.","specificNumbers":"","methodology":"Summary of multiple chinchilla studies testing liraglutide across varied conditions: low (3-5 psi) and high (15-25 psi) blast intensities, 3 and 6 repeated blasts, single and recurrent exposure patterns, and open versus earplug-protected ears. Animals were divided into pre-blast treatment, post-blast treatment, and control groups. Outcomes were assessed via auditory brainstem response (ABR) testing and cochlear tissue histology.","limitations":"These are animal studies in chinchillas, which, while well-established for hearing research, do not perfectly model human blast exposure or hearing physiology. The optimal dose, timing, and duration of liraglutide treatment for hearing protection in humans are unknown. The studies summarized here used various conditions, making direct comparisons between experiments complex. Long-term follow-up beyond the study periods was not reported."},{"rthcId":"RPEP-11619","title":"Vaccination with synthetic long peptide and CpG 2395 in AddaVax induces potent anti-tumor effects.","authors":"Jiang, Shanshan; Zhao, Shuqi; Zhao, Qiaojiajie; Wang, Yinfang; Zhang, Weihua; Feng, Yangmeng; Zhang, Lijie","year":2025,"journal":"Experimental biology and medicine (Maywood, N.J.), 250, 10509","doi":"10.3389/ebm.2025.10509","pmid":"40395227","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11620","title":"Enhancing DNA Vaccine Delivery Through Stearyl-Modified Cell-Penetrating Peptides: Improved Antigen Expression and Immune Response In Vitro and In Vivo.","authors":"Jiang, Sheng; Zu, Cheng; Wang, Bin; Zhong, Yiwei","year":2025,"journal":"Vaccines, 13(1)","doi":"10.3390/vaccines13010094","pmid":"39852873","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The stearyl-modified cell-penetrating peptide S-Cr9T formed stable complexes with plasmid DNA and significantly enhanced both cellular uptake and transfection efficiency in vitro. Optimal performance was achieved at a nitrogen-to-phosphate (N/P) ratio of 0.25.\n\nHigh-content imaging showed that S-Cr9T-plasmid complexes stably adhered to cell membranes, promoting efficient intracellular delivery. In vivo, S-Cr9T significantly increased antigen expression and triggered robust immune responses: a threefold increase in IFN-γ secretion (a key marker of cellular immunity) and several hundred-fold increases in antibody levels compared to controls.\n\nThese results demonstrate that lipid modification of cell-penetrating peptides can overcome the major delivery barrier limiting DNA vaccine efficacy.","whyItMatters":"DNA vaccines are cheaper, more stable, and easier to manufacture than traditional vaccines, but their poor cellular uptake has limited their real-world use. This peptide-based delivery system addresses that core problem without requiring viral vectors or complex nanoparticle formulations. The dramatic improvement in immune response suggests this approach could make DNA vaccines viable for a wider range of diseases.","specificNumbers":"","methodology":"The researchers designed S-Cr9T by adding a stearyl (fatty acid) modification to a cell-penetrating peptide. They tested it in vitro using cell culture assays measuring plasmid stability, transfection efficiency, and high-content imaging of cellular uptake. In vivo testing in animals measured antigen expression, IFN-γ secretion (via immunoassay), and antibody levels to assess immune response strength.","limitations":"The abstract does not specify the animal model used or the sample sizes for in vivo experiments. The several hundred-fold antibody increase is described qualitatively rather than with precise figures. Long-term immune durability was not assessed. As a preclinical study, human immune responses may differ significantly. The optimal N/P ratio was determined in vitro and may need adjustment for clinical applications."},{"rthcId":"RPEP-11621","title":"Deep Learning-Driven Optimization of Antihypertensive Properties from Whey Protein Hydrolysates: A Multienzyme Approach.","authors":"Jiang, Shuai; Mo, Fan; Li, Wenhan; Yang, Sirui; Li, Chunbao; Jiang, Ling","year":2025,"journal":"Journal of agricultural and food chemistry, 73(2), 1373-1388","doi":"10.1021/acs.jafc.4c10830","pmid":"39721995","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The AI-optimized multienzyme combination MC5 achieved 89.08% ACE inhibition at 1 mg/mL, significantly outperforming single-enzyme hydrolysis. After simulated digestion, ACE inhibition decreased by only 6.87%. In hypertensive rats, MC5 reduced systolic blood pressure to 125 mmHg and diastolic to 89 mmHg. The treatment significantly lowered TNF-α and IL-6, increased SOD, GSH-Px, GR, and CAT activity, reduced serum renin (1.25-fold) and ET-1 (1.04-fold), and increased NO content 3.15-fold. Four potent peptides were identified: LPEW, LKPTPEGDL, LNYW, and LLL.","whyItMatters":"This study bridges AI, food science, and cardiovascular health. By using deep learning to optimize enzyme combinations, the researchers achieved ACE inhibition levels (89%) approaching pharmaceutical-grade potency from a common food protein. The critical addition of in vivo data — showing actual blood pressure reduction in rats — elevates this beyond typical in vitro peptide studies. The digestion stability finding (only 6.87% loss) addresses a major concern with food-derived bioactive peptides.","specificNumbers":"","methodology":"Large language models were used to predict optimal multienzyme combinations for whey protein hydrolysis. The best combination (MC5) was validated through in vitro ACE inhibition assays and simulated gastrointestinal digestion stability testing. In vivo efficacy was assessed in spontaneously hypertensive rats, measuring blood pressure, inflammatory markers, antioxidant enzymes, renin, ET-1, and NO. Molecular docking identified the most potent individual peptide sequences and their ACE binding modes.","limitations":"The in vivo study was conducted in spontaneously hypertensive rats, which may not fully represent human hypertension. Specific rat numbers per group and treatment duration were not detailed. Human clinical trials are needed. The four identified peptides need individual testing to confirm their contribution to the overall effect. Manufacturing scale-up and cost-effectiveness were not addressed. The LLM methodology details were not fully described."},{"rthcId":"RPEP-11622","title":"CREB-KIF1A-CGRP-positive feedback loop drives central sensitization in chronic migraine.","authors":"Jiang, Wei; Yu, Peng; Shi, Yan-Min; Zhang, Li-Xi; Cai, Meng-Tan; Yang, Yu; Dong, Ming","year":2025,"journal":"The journal of headache and pain, 26(1), 194","doi":"10.1186/s10194-025-02147-4","pmid":"41029476","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Researchers discovered a self-reinforcing feedback loop — CREB→KIF1A→CGRP→CREB — that drives chronic migraine. CREB directly activates transcription of KIF1A (a motor protein), which physically associates with CGRP and promotes its transport and expression. CGRP signaling then feeds back to reactivate CREB, creating a positive loop. Disrupting any component of this axis — inhibiting CREB, knocking down KIF1A, or blocking the CGRP receptor — effectively reduced migraine-like pain behaviors and molecular markers of central sensitization in mice.","whyItMatters":"While CGRP is a proven migraine target, why it stays elevated in chronic migraine has been unclear. This study explains the mechanism: a feedback loop keeps CGRP production running. Understanding this loop reveals new upstream targets (CREB, KIF1A) that could be blocked to treat chronic migraine, potentially offering alternatives for patients who don't respond to anti-CGRP antibodies. It also explains how episodic migraine may become chronic through self-sustaining CGRP signaling.","specificNumbers":"NTG-induced chronic migraine model · CREB directly binds Kif1a promoter (ChIP/luciferase confirmed) · KIF1A physically associates with CGRP (Co-IP confirmed) · Kif1a knockdown reduced CGRP in synaptic vesicles · CGRP receptor blockade inhibited CREB/KIF1A activation","methodology":"Chronic migraine was modeled in mice using repeated nitroglycerin injections. Researchers used behavioral testing (thermal/mechanical allodynia), molecular analyses (immunoblotting, qPCR, immunofluorescence), ChIP and dual-luciferase assays (to confirm CREB binds Kif1a promoter), co-immunoprecipitation (KIF1A-CGRP interaction), synaptosomal analysis (vesicle CGRP levels), and pharmacological interventions (Forskolin/CREB agonist, 666-15/CREB inhibitor, Kif1a knockdown/overexpression, Olcegepant/CGRP receptor antagonist).","limitations":"This is a mouse model study using nitroglycerin-induced migraine, which may not fully recapitulate human chronic migraine. The interventions (gene knockdown, CREB inhibitors) are not yet available as clinical treatments. The feedback loop was characterized primarily in spinal trigeminal neurons and Neuro-2a cells, and additional brain regions involved in migraine were not examined."},{"rthcId":"RPEP-11623","title":"Biguanide-functionalized peptide mimics effectively combat drug-resistant ESKAPE pathogens and meningitis.","authors":"Jiang, Weinan; Zhou, Min; Chen, Kang; Xiao, Ximian; Shi, Jia; Zhang, Haodong; Xie, Jiayang; Chen, Sheng; Chen, Minzhang; Cong, Zihao; Liu, Longqiang; Wu, Yueming; Liu, Runhui","year":2025,"journal":"Nature communications, 17(1), 336","doi":"10.1038/s41467-025-67044-5","pmid":"41365877","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11624","title":"Enhanced delivery of camptothecin to colorectal carcinoma using a tumor-penetrating peptide targeting p32.","authors":"Jiang, Yanhao; Wang, Zhiren; Li, Wenpan; Ma, Teng; Li, Mengwen; Wu, Shuang; Lin, Ethan; Flader, Karlie Elizabeth; Ma, Mengjiao; Chang, Mengyang; Li, Hongmin; Wang, Wei; Lu, Jianqin","year":2025,"journal":"Acta biomaterialia, 200, 629-640","doi":"10.1016/j.actbio.2025.05.036","pmid":"40379119","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11625","title":"Dodecapeptides derived from human cathelicidin with potent activity against carbapenem-resistant Acinetobacter baumannii.","authors":"Jiang, Yiyi; Zhao, Gaomei; Gong, Yali; Chen, Yin; Li, Chenwenya; Han, Songling; Deng, Youcai; Zhao, Jinghong; Wang, Junping; Wang, Cheng","year":2025,"journal":"European journal of medicinal chemistry, 289, 117477","doi":"10.1016/j.ejmech.2025.117477","pmid":"40056800","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"From 28 engineered dodecapeptides (12 amino acids) based on the antibacterial core of human cathelicidin, two leads emerged: d12 (linear) and d24 (hydrocarbon-stapled). Both killed carbapenem-resistant A. baumannii clinical isolates with MICs of 2.5–20 µg/mL by binding and penetrating bacterial membranes in a lipid A-dependent manner. In two mouse infection models — irradiation-assisted pulmonary infection and intra-abdominal sepsis — both peptides significantly reduced bacterial load and improved survival. The stapled d24 outperformed d12 in the sepsis model due to improved resistance to enzymatic degradation.","whyItMatters":"CRAB is classified by the WHO as a critical-priority pathogen with essentially no reliable treatment options. These short peptides derived from the human immune system offer a promising new therapeutic approach — they are potent, easy to synthesize, and the stapling technology addresses a major challenge in peptide drug development (enzymatic degradation). The in vivo efficacy data is particularly encouraging.","specificNumbers":"28 dodecapeptides synthesized · MIC 2.5–20 µg/mL against CRAB isolates · 2 lead candidates (d12 linear, d24 stapled) · lipid A-dependent membrane penetration · improved mouse survival in 2 infection models","methodology":"28 dodecapeptides were designed through site-directed mutation and all-hydrocarbon stapling of the KR12 antibacterial core of human cathelicidin LL-37. In vitro testing included MIC assays against CRAB clinical isolates, membrane binding and penetration studies, and biocompatibility assessments. In vivo efficacy was tested in two mouse models: irradiation-assisted local pulmonary infection and intra-abdominal sepsis with CRAB.","limitations":"Preclinical study — efficacy in humans has not been tested. The mouse infection models used irradiation-assisted immunosuppression, which may not reflect all clinical scenarios. Long-term toxicity and pharmacokinetic profiles were not detailed in the abstract. Cost comparison to existing therapies was not provided."},{"rthcId":"RPEP-11626","title":"Why does GLP-1 agonist combined with GIP and/or GCG agonist have greater weight loss effect than GLP-1 agonist alone in obese adults without type 2 diabetes?","authors":"Jiang, Yuchen; Zhu, Huijuan; Gong, Fengying","year":2025,"journal":"Diabetes, obesity & metabolism, 27(3), 1079-1095","doi":"10.1111/dom.16106","pmid":"39592891","tags":[],"studyType":"review","evidenceStrength":"moderate","keyFinding":"This review explains the mechanisms behind why multi-receptor agonists produce greater weight loss than single GLP-1 agonists alone in non-diabetic obese adults. The dual GIP/GLP-1 agonist tirzepatide activates both receptors, enhancing appetite suppression and metabolic effects beyond what GLP-1 alone achieves. GLP-1/glucagon dual agonists add glucagon's ability to increase energy expenditure and fat burning. Triple GLP-1/GIP/glucagon agonists combine all three mechanisms — appetite reduction, enhanced metabolic rate, and improved fat utilization — potentially offering the greatest weight loss of all. Each additional receptor target adds complementary mechanisms that address different aspects of energy balance.","whyItMatters":"The evolution from single to dual to triple agonists represents one of the most rapidly advancing areas of drug development. Understanding why adding GIP and/or glucagon signaling to GLP-1 therapy improves outcomes is essential for clinicians choosing between available medications (semaglutide vs. tirzepatide) and for the pharmaceutical industry developing next-generation drugs (retatrutide and others). The mechanistic explanations also help predict potential side effects and identify which patients might benefit most from each approach.","specificNumbers":"3 multi-receptor platforms reviewed: GLP-1/GIP, GLP-1/GCG, GLP-1/GIP/GCG · FDA-approved: liraglutide, semaglutide (mono), tirzepatide (dual)","methodology":"Narrative review summarizing the pharmacological mechanisms of GLP-1 mono-agonists, GLP-1/GIP dual agonists, GLP-1/glucagon dual agonists, and GLP-1/GIP/glucagon triple agonists for obesity. The review synthesizes evidence from preclinical and clinical studies to explain the mechanistic basis for the enhanced weight loss efficacy of multi-receptor targeting.","limitations":"As a narrative review, this does not perform systematic literature search or meta-analysis. Head-to-head clinical trials directly comparing all these drug classes are limited. The review focuses on non-diabetic obesity, and the mechanisms may differ in patients with type 2 diabetes. Triple agonists (like retatrutide) have limited clinical data — most evidence is from early-phase trials. Long-term safety data for dual and triple agonists is still accumulating."},{"rthcId":"RPEP-11627","title":"Immune Dysregulation in Obesity.","authors":"Jiang, Zewen; Tabuchi, Chihiro; Gayer, Sarah G; Bapat, Sagar P","year":2025,"journal":"Annual review of pathology, 20(1), 483-509","doi":"10.1146/annurev-pathmechdis-051222-015350","pmid":"39854190","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11628","title":"Lipoprotein(a) and the risk of type I cardiorenal syndrome in patients with coronary artery disease: A retrospective clinical study.","authors":"Jiang, Zhenhua; Ma, Hailiang; Meng, Jianqiang; Zhu, Dewen; Lu, Yuanben","year":2025,"journal":"International journal of cardiology. Heart & vasculature, 56, 101568","doi":"10.1016/j.ijcha.2024.101568","pmid":"39720339","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11629","title":"Discovery of novel angiotensin-converting enzyme inhibitory peptides by in silico and in vitro studies.","authors":"Jiao, Fenglin; Yang, Jinlin; Wang, Fangfang; Peng, Shanli; Zhou, Bo","year":2025,"journal":"RSC advances, 15(47), 39885-39897","doi":"10.1039/d5ra06104k","pmid":"41127195","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Using 3D-QSAR (quantitative structure-activity relationship) modeling with both CoMFA and CoMSIA methods, the researchers developed reliable predictive models for ACE inhibitory peptide activity. The CoMFA model achieved cross-validated R² of 0.660 and predictive R² of 0.667, while CoMSIA achieved 0.646 and 0.645 respectively.\n\nMolecular docking revealed how these peptides bind at the ACE active site, with binding characteristics consistent with the 3D-QSAR contour maps. Based on these computational insights, three novel tripeptides were designed as prospective ACE inhibitors. All three showed effective ACE inhibition when tested experimentally using the DOJINDO ACE Kit-WST reagent, validating the computational design approach.","whyItMatters":"ACE inhibitors are among the most prescribed medications worldwide for hypertension, but current synthetic drugs can cause unpleasant side effects. Bioactive peptides from food sources have shown ACE-inhibiting potential with fewer side effects, but discovering effective ones by trial and error is slow and expensive. This computational approach accelerates the discovery process, potentially leading to natural peptide-based blood pressure treatments with better safety profiles.","specificNumbers":"","methodology":"The researchers employed a multi-step computational and experimental approach. First, they built 3D-QSAR models using CoMFA (comparative molecular field analysis) and CoMSIA (comparative molecular similarity indices analysis) based on known ACE inhibitory peptides. Molecular docking was then used to explore how peptides bind at the ACE active site. Based on these computational insights, three novel tripeptides were designed. Finally, the designed peptides were experimentally validated for ACE inhibitory activity using the DOJINDO ACE Kit-WST reagent box.","limitations":"The study validated ACE inhibition only in a cell-free enzymatic assay — no cell-based studies, animal models, or human data were reported. The 3D-QSAR models had moderate predictive power (R² ~0.65), leaving room for false positives in peptide design. Oral bioavailability and stability of these tripeptides in the gastrointestinal tract were not assessed. Actual blood pressure-lowering effects in living organisms remain to be demonstrated."},{"rthcId":"RPEP-11630","title":"Peptide-functionalized periodic mesoporous silica nanoparticles for monocyte-specific TET3 Silencing enhance cardiac repair after acute myocardial infarction.","authors":"Jin, Hao; Ding, Jiandong; Zhang, Xiaoguo; Cheng, Shouquan; Zhang, Yahao; Wu, Yong; Liu, Cihui; Yang, Sirui; Zhang, Anjian; Ma, Genshan; Lu, Wenbin","year":2025,"journal":"Journal of nanobiotechnology, 23(1), 743","doi":"10.1186/s12951-025-03782-4","pmid":"41299461","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Key findings across multiple models:\n\n- TET3 expression in circulating monocytes was identified as an independent predictor of heart attack occurrence and patient prognosis in a clinical cohort\n- A monocyte-targeting nanoparticle system was engineered using: periodic mesoporous silica loaded with siTET3, PEI/PEG coating, and a CD14 receptor-recognizing peptide (Cys-Gly-Trp-Arg-Arg-Arg-NH₂)\n- In vitro: successfully reprogrammed inflammatory monocytes with attenuated pro-inflammatory phenotypes\n- In mouse AMI model: markedly reduced infarct size and myocardial fibrosis\n- In pig AMI model: substantial suppression of cardiac inflammation and improved post-infarction outcomes after systemic administration","whyItMatters":"Heart attacks remain a leading cause of death worldwide, and current treatments focus on restoring blood flow but do little to prevent the inflammatory damage that follows. This targeted approach addresses the inflammatory component by specifically reprogramming the immune cells that cause post-heart attack damage. The validation in a large animal (pig) model makes this particularly promising for clinical translation.","specificNumbers":"","methodology":"The study combined clinical data analysis (TET3 as predictor), nanoparticle engineering (PMS loaded with siTET3, surface-modified with PEI, PEG, and CD14-targeting peptide), in vitro monocyte reprogramming assays, in vivo mouse AMI models, and translational validation in a porcine (pig) AMI model with systemic administration.","limitations":"While validated in both mouse and pig models, human clinical trials are needed. The CD14-targeting peptide could also affect other CD14-expressing cells beyond monocytes. Long-term effects of TET3 silencing on immune function are unknown. Manufacturing scalability of the nanoparticle system for clinical use was not addressed. The clinical cohort data identified TET3 as a predictor, but causation needs further confirmation."},{"rthcId":"RPEP-11631","title":"Small-molecule CGRP antagonist atogepant does not affect cortical spreading depression susceptibility in rats.","authors":"Jin, Xuyan; Morais, Andreia; Sasaki, Yuichi; Zhai, Qingling; Banerjee, Pradeep; Harriott, Andrea; Ayata, Cenk","year":2025,"journal":"The journal of headache and pain, 26(1), 177","doi":"10.1186/s10194-025-02127-8","pmid":"40764901","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11632","title":"Analysis of the Efficacy of Polyenyl Phosphatidylcholine in Combination with Liraglutide in Nonalcoholic Fatty Liver Disease and the Effect of Omentin-1 and Vaspin Expression.","authors":"Jin, Yao; Liu, Tong; Tong, Zhiqiang; Dong, Mei","year":2025,"journal":"Alternative therapies in health and medicine, 31(4), 273-277","doi":null,"pmid":"38814610","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Combining polyene phosphatidylcholine (PPC) with the GLP-1 peptide agonist liraglutide achieved a 95% clinical effectiveness rate in NAFLD patients versus 83.33% for PPC alone. The combination therapy produced significantly greater reductions in liver enzymes (ALT, AST, GGT), vaspin, and FGF21, along with greater increases in the beneficial adipokine omentin-1.","whyItMatters":"NAFLD is one of the most common liver diseases worldwide. This study demonstrates that adding the peptide drug liraglutide to standard phospholipid therapy significantly improves outcomes, suggesting a role for GLP-1 receptor agonists beyond their well-known metabolic benefits.","specificNumbers":"n=120 · 95% vs 83.33% clinical effectiveness · 12-week treatment · p<0.05","methodology":"Randomized controlled trial with 120 NAFLD patients split equally into two groups. The control group received PPC alone while the observation group received PPC plus liraglutide for 12 weeks. Researchers measured clinical effectiveness, liver enzymes, and adipokine levels before and after treatment.","limitations":"Relatively small sample size of 120 patients. The 12-week treatment period may not capture long-term outcomes. The abstract does not detail randomization methods, blinding, or specific dosing. Published in a complementary/alternative medicine journal rather than a hepatology-focused journal."},{"rthcId":"RPEP-11633","title":"Effects of gut microbiota and metabolites on the host defense peptide expression.","authors":"Jin, Yuanli; Gong, Tao; Lu, Xiaoxi; Wang, Yizhen; Cheng, Yuanzhi","year":2025,"journal":"Applied microbiology and biotechnology, 109(1), 10","doi":"10.1007/s00253-024-13400-2","pmid":"39825892","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11634","title":"The role of GLP-1 receptor in pain disorders and its pharmacological properties.","authors":"Jing, Feng; Zeng, Ying; Yu, Qin-Ling; Fu, Chao-Ju","year":2025,"journal":"European journal of pharmacology, 1008, 178345","doi":"10.1016/j.ejphar.2025.178345","pmid":"41207354","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11635","title":"Effects of bisoprolol combined with torasemide on cardiac electrophysiology in patients with acute myocardial infarction and heart failure.","authors":"Jing, Li; Shi, Qiangwei; Zhao, Shihao","year":2025,"journal":"Frontiers in physiology, 16, 1629758","doi":"10.3389/fphys.2025.1629758","pmid":"40843126","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11636","title":"Malnutrition is Common in Patients Utilizing Glucagon-Like Peptide-1 Agonists Prior to Total Joint Arthroplasty.","authors":"Jodoin, Zachary; Young, William H; Sheikh, Daanish; Pena, Belinda; Moore, Chance C; Buttacavoli, Frank","year":2025,"journal":"Arthroplasty today, 35, 101865","doi":"10.1016/j.artd.2025.101865","pmid":"41079677","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11637","title":"Regulation of LEAP2 by insulin and glucagon in mice and humans.","authors":"Johansen, Valdemar Brimnes Ingemann; Gradel, Anna Katrina Jógvansdóttir; Holm, Stephanie Kjærulff; Cuenco, Joyceline; Merrild, Christoffer; Petersen, Natalia; Demozay, Damien; Mani, Bharath Kumar; Suppli, Malte Palm; Grøndahl, Magnus F G; Lund, Asger Bach; Knop, Filip Krag; Prada-Medina, Cesar A; Hogendorf, Wouter Frederik Johan; Lykkesfeldt, Jens; Merkestein, Myrte; Sakamoto, Kei; Holst, Birgitte; Clemmensen, Christoffer","year":2025,"journal":"Cell reports. Medicine, 6(3), 101996","doi":"10.1016/j.xcrm.2025.101996","pmid":"40056903","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11638","title":"Investigating nutrient intake during use of glucagon-like peptide-1 receptor agonist: a cross-sectional study.","authors":"Johnson, Brittany; Milstead, Mary; Thomas, Olena; McGlasson, Tyler; Green, Lauren; Kreider, Rachel; Jones, Rachel","year":2025,"journal":"Frontiers in nutrition, 12, 1566498","doi":"10.3389/fnut.2025.1566498","pmid":"40352260","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11639","title":"Diet quality and nutrient distribution while using glucagon-like-peptide-1 receptor agonist: A secondary cross-sectional analysis.","authors":"Johnson, Brittany V B; Milstead, Mary; Green, Lauren; Kreider, Rachel; Jones, Rachel","year":2025,"journal":"Obesity pillars, 16, 100195","doi":"10.1016/j.obpill.2025.100195","pmid":"40852562","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11640","title":"Dietary supplement considerations during glucagon-like Peptide-1 receptor agonist treatment: A narrative review.","authors":"Johnson, Brittany V B; Milstead, Mary; Kreider, Rachel; Jones, Rachel","year":2025,"journal":"Obesity pillars, 16, 100209","doi":"10.1016/j.obpill.2025.100209","pmid":"41368199","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11641","title":"Broad Immunomodulatory Effects of the Dipeptidyl Peptidase-1 Inhibitor Brensocatib in Bronchiectasis: Data from the Phase 2, Double-Blind, Placebo-controlled WILLOW Trial.","authors":"Johnson, Emma D; Long, Merete B; Perea, Lidia; Shih, Vivian H; Fernandez, Carlos; Teper, Ariel; Cipolla, David; McIntosh, Eve; Galloway, Rachel; Eke, Zsofia; Shuttleworth, Morven; Hull, Rebecca; Spinou, Arietta; De Soyza, Anthony; Ringshausen, Felix C; Goeminne, Pieter; Lorent, Natalie; Haworth, Charles; Loebinger, Michael R; Blasi, Francesco; Shteinberg, Michal; Aliberti, Stefano; Polverino, Eva; Sibila, Oriol; Shoemark, Amelia; Mange, Kevin; Huang, Jeffrey T J; Stobo, Jamie; Chalmers, James D","year":2025,"journal":"American journal of respiratory and critical care medicine, 211(5), 770-778","doi":"10.1164/rccm.202408-1545OC","pmid":"39938076","tags":[],"studyType":"phase 2 clinical trial (biomarker analysis)","evidenceStrength":"moderate","keyFinding":"The dipeptidyl peptidase-1 (DPP-1) inhibitor brensocatib — which blocks the enzyme that activates destructive neutrophil proteins — had broad immunomodulatory effects beyond its known impact on serine proteases in bronchiectasis patients. Treatment increased the antimicrobial peptides SLPI and α-defensin-3 in sputum, reduced the inflammatory mucin MUC5AC, and significantly altered 15 cytokines and chemokines including CXCL10, CCL8, CCL7, CCL3, and IL-6. These changes were consistent across both doses (10 mg and 25 mg) and validated in an independent European bronchiectasis cohort. The findings reveal that brensocatib rebalances the inflammatory environment in the airways much more broadly than just reducing protease activity.","whyItMatters":"Bronchiectasis is a chronic lung condition driven by a vicious cycle of infection, neutrophilic inflammation, and airway damage. Most treatments target infection (antibiotics) or mucus clearance, but none effectively break the inflammatory cycle. Brensocatib's ability to simultaneously reduce destructive proteases, increase protective antimicrobial peptides, decrease mucin overproduction, and modulate multiple inflammatory pathways suggests it could be the first therapy to comprehensively address the underlying pathology rather than just managing symptoms.","specificNumbers":"n=256 (82 brensocatib 10mg, 87 brensocatib 25mg, 87 placebo) · 215 with sputum for analysis · SLPI and α-defensin-3↑ · MUC5AC↓ · 15 cytokines/chemokines significantly changed · 24-week treatment + 4-week follow-up","methodology":"Biomarker analysis from the WILLOW phase 2 trial (double-blind, placebo-controlled, randomized). Sputum was collected at baseline, 4 weeks, 24 weeks (end of treatment), and 28 weeks (4 weeks post-treatment). Antimicrobial peptides (SLPI, α-defensin-3) were measured by ELISA, mucin MUC5AC by mass spectrometry, myeloperoxidase by immunoassay, and 45 inflammatory cytokines using the Olink Target 48 assay. Findings were validated against the European BRIDGE bronchiectasis cohort.","limitations":"This is a biomarker sub-analysis of a phase 2 trial, not the primary efficacy endpoint. Changes in biomarkers don't necessarily translate to clinical improvement. The study population had non-cystic fibrosis bronchiectasis, so results may not apply to CF bronchiectasis. Sputum analysis was available for only a subset of randomized patients (215 of 256). The relationship between individual biomarker changes and clinical outcomes (exacerbations, lung function) is not fully characterized in this analysis."},{"rthcId":"RPEP-11642","title":"Impact of Digital Engagement on Weight Loss Outcomes in Obesity Management Among Individuals Using GLP-1 and Dual GLP-1/GIP Receptor Agonist Therapy: Retrospective Cohort Service Evaluation Study.","authors":"Johnson, Hans; Huang, David; Liu, Vivian; Ammouri, Mahmoud Al; Jacobs, Christopher; El-Osta, Austen","year":2025,"journal":"Journal of medical Internet research, 27, e69466","doi":"10.2196/69466","pmid":"40164173","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Of 57,975 participants, 54.2% were classified as engaged and 45.8% as non-engaged with the digital platform. At month 3: engaged lost 9% vs non-engaged 5.9% (P<0.001, Cohen d=0.89 — large effect). At month 5: engaged lost 11.53% vs non-engaged 8% (P<0.001, Cohen d=0.56 — moderate effect). Tirzepatide users achieved greater weight loss than semaglutide users at month 5 (13.9% vs 9.5%, P<0.001). Engaged participants were significantly more likely to achieve ≥5%, ≥10%, and ≥15% weight loss thresholds at all time points.","whyItMatters":"With millions now taking GLP-1 drugs, optimizing their effectiveness is a major healthcare priority. This study — one of the largest real-world GLP-1 datasets published — demonstrates that behavioral support through digital platforms meaningfully amplifies drug effectiveness. A 3-percentage-point improvement in weight loss translates to clinically significant additional health benefits. This supports pairing medication with structured behavioral programs rather than prescribing drugs alone.","specificNumbers":"","methodology":"Retrospective cohort service evaluation using data from the Voy weight loss digital health platform (UK, February 2023-August 2024). Included 57,975 adults (BMI ≥30 or ≥27.5 with comorbidities) initiating semaglutide or tirzepatide. Engagement defined by coaching session attendance, app usage frequency, and weight tracking regularity. Weight loss assessed over 5 months. Statistics: chi-square tests, independent t-tests, Kaplan-Meier survival analysis, Cohen d effect sizes.","limitations":"Retrospective observational design — engaged users may differ systematically from non-engaged users in motivation, socioeconomic status, and baseline health. Selection bias is likely, as more motivated individuals may both engage more and lose more weight regardless of the app. The 5-month follow-up is relatively short for obesity management. Data came from a commercial digital platform, introducing potential reporting and measurement biases. The specific components of engagement (coaching vs. tracking vs. app use) weren't separately analyzed for their contributions. UK-specific healthcare and cultural context may limit generalizability."},{"rthcId":"RPEP-11643","title":"Early Life Stress induces brain-wide electrical network predisposition to migraine.","authors":"Johnson, Micah; Eberle, Maureen; Hultman, Ian; Zhang, Xinyu; Filali, Yassine; Hing, Benjamin; Matkovich, Molly; Jimenez, Alli; Mitchell, Sara; Adegboyo, Anjayooluwa; Velamuri, Radha; Miller, Julia; Chan, Kung-Sik; Srivastava, Sanvesh; Hultman, Rainbo","year":2025,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2024.11.14.622885","pmid":"40462923","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11644","title":"Endomorphin-2 (Endo2) and substance P (SubP) co-application attenuates SubP-induced excitation and alters frequency plasticity in neonatal rat in vitro preparations.","authors":"Johnson, Stephen M; Johnson, Sarah M; Watters, Jyoti J; Baker, Tracy L","year":2025,"journal":"Respiratory physiology & neurobiology, 331, 104351","doi":"10.1016/j.resp.2024.104351","pmid":"39303801","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11645","title":"Semaglutide Exacerbates Stunting in Growth-Impaired Juvenile Male Mice via Reduced Energy Metabolism.","authors":"Joly, Amélie; Rebiffé, Lucas; Dusabyinema, Yves; Dellinger, Julien; Caillon, Estelle; Gauthier, Karine; Leulier, François; De Vadder, Filipe","year":2025,"journal":"Journal of the Endocrine Society, 9(11), bvaf158","doi":"10.1210/jendso/bvaf158","pmid":"41163813","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11646","title":"GLP-1 and the Neurobiology of Eating Control: Recent Advances.","authors":"Jones, Lauren A; Brierley, Daniel I","year":2025,"journal":"Endocrinology, 166(2)","doi":"10.1210/endocr/bqae167","pmid":"39813121","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11647","title":"GLP-1 Receptor Agonists in Diabetes and Obesity: A Case Report and Review of Bowel Obstruction Risks and Management.","authors":"Jones, Matthew; Cappola, James J","year":2025,"journal":"Cureus, 17(4), e81891","doi":"10.7759/cureus.81891","pmid":"40342457","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A 55-year-old woman with obesity, type 2 diabetes, and a prior history of small bowel obstruction developed severe abdominal pain and was diagnosed with small bowel obstruction after initiating semaglutide therapy. The obstruction was attributed to the drug's mechanism of slowing gastric emptying and altering the migrating motor complex, compounded by her preexisting GI vulnerability.\n\nThe patient was treated conservatively with nasogastric decompression and bowel rest, and her condition resolved. However, the case prompted reassessment of continued GLP-1 RA therapy, underscoring that the benefits of glycemic control must be weighed against GI risks in susceptible individuals.","whyItMatters":"GLP-1 receptor agonists are among the most prescribed medications worldwide for diabetes and weight loss. As their use expands rapidly, understanding rare but serious side effects like bowel obstruction is critical — especially for patients with prior GI issues who may be at elevated risk. This case reinforces the importance of personalized prescribing decisions.","specificNumbers":"","methodology":"This was a single-patient case report combined with a literature review. The authors documented the clinical presentation, diagnosis, and treatment of a patient who developed bowel obstruction after starting semaglutide, then reviewed existing evidence on GLP-1 receptor agonist-associated gastrointestinal complications.","limitations":"As a single case report, this study cannot establish causation or quantify how common bowel obstruction is among GLP-1 RA users. The patient had a preexisting history of bowel obstruction, making it difficult to determine how much the medication versus her underlying condition contributed. Larger epidemiological studies are needed to assess the true incidence of this complication."},{"rthcId":"RPEP-11648","title":"Effects of peptides derived from active sites of visfatin on wound healing.","authors":"Joo, Bo Sun; Baek, Ju-Hwa; Park, Min Jung; Choi, Hyunseok; Choi, Ji Myung; Lee, Jae Woo","year":2025,"journal":"Scientific reports, 15(1), 22169","doi":"10.1038/s41598-025-06751-x","pmid":"40595107","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11649","title":"Impact of Glucagon-Like Peptide-1 Receptor Agonists on Age-Related Macular Degeneration at a Tertiary Ophthalmology Center.","authors":"Joo, Julia H; Zhao, Alison H; Chalasani, Meghana; Allan, Kevin C; Rachitskaya, Aleksandra V","year":2025,"journal":"Ophthalmology. Retina","doi":"10.1016/j.oret.2025.12.014","pmid":"41443408","tags":["glp-1","eye-health"],"studyType":"retrospective-cohort","evidenceStrength":"moderate","keyFinding":"GLP-1 receptor agonist use was associated with a significantly lower risk of developing nonexudative age-related macular degeneration (AMD) compared to metformin, insulin, and SGLT-2 inhibitors. After 3 years of use, GLP-1 users had 75% lower AMD risk versus metformin (RR 0.25), 72% lower risk versus insulin (RR 0.28), and 58% lower risk versus SGLT-2 inhibitors (RR 0.42).\n\nIn the more rigorous propensity score-matched analysis controlling for additional confounders (BMI, hypertension, CKD, diabetes duration), the reduced risk remained significant compared to insulin (HR 0.45; 95% CI 0.27–0.76). This suggests GLP-1 drugs may have a protective effect on the retina independent of blood sugar control, since all comparator groups were also on glucose-lowering medications.","whyItMatters":"AMD is the leading cause of vision loss in people over 50 in developed countries, and there's no treatment for the dry (nonexudative) form. If GLP-1 drugs truly reduce AMD risk — as this large study suggests — it could represent an unexpected protective benefit for the tens of millions of people taking these medications. The finding is especially intriguing given the SUSTAIN-6 retinopathy signal, suggesting GLP-1 drugs may have complex, nuanced effects on the eye that differ between diabetic retinopathy and AMD.","specificNumbers":"","methodology":"Retrospective cohort study at a tertiary ophthalmology center analyzing patients aged ≥50 with at least 1 year of drug use between 2016 and 2025. Compared 30,515 GLP-1RA users against 48,906 SGLT-2i users, 286,066 metformin users, and 164,361 insulin users. After propensity score matching, each cohort included 7,561 patients. Logistic regression controlled for age, sex, race, smoking status, and HbA1c. Cox proportional hazards validation additionally matched for BMI, hypertension, CKD, and diabetes duration. Patients with diabetic macular edema, severe diabetic retinopathy, or prior retinal surgery were excluded.","limitations":"This is a retrospective observational study from a single center — it shows association, not causation. Residual confounding is possible despite propensity score matching. The more rigorous CPH analysis in matched cohorts only confirmed the benefit versus insulin (not metformin or SGLT-2i). The study focused on nonexudative (dry) AMD only. GLP-1 users may differ from other drug users in ways not captured by the measured confounders."},{"rthcId":"RPEP-11650","title":"Glucagon-Like Peptide-1 Receptor Agonist Use and the Risk of Adverse Cardiac and Kidney Outcomes Among Patients With Systemic Lupus Erythematosus and Lupus Nephritis.","authors":"Jorge, April; Patel, Aakash V; Zhou, Baijun; Zhang, Lingxiao; Choi, Hyon","year":2025,"journal":"Arthritis & rheumatology (Hoboken, N.J.)","doi":"10.1002/art.43403","pmid":"40994310","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11651","title":"The role of intra-abdominal pressure and point of care ultrasound to guide decongestive therapies in acute heart failure.","authors":"Josa-Laorden, C; Campos-Saenz de Santamaría, A; Crespo-Aznarez, S; Pérez-Silvestre, J; Montero-Hernandez, E; Llacer-Iborra, P; Torres-Macho, J; Méndez-Bailon, M; Morales-Rull, J L; Salamanca-Bautista, P; Fernández-Villa, N; Torres-Courchoud, I; Vázquez-Ronda, M A; Martínez-Gutiérrez, R; Serrano-Irigoyen, P; García-Lorente, N; Trullas, J C; Cobo-Marcos, M; Pinilla, M J; Sánchez-Marteles, M; Rubio-Gracia, J","year":2025,"journal":"ESC heart failure, 12(5), 3741-3749","doi":"10.1002/ehf2.15380","pmid":"40739778","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11652","title":"Comparative Effectiveness of SGLT2 Inhibitors and Semaglutide in Diabetic Nephropathy: A Retrospective Observational Study.","authors":"Joseph, Jimmy","year":2025,"journal":"Cureus, 17(7), e87399","doi":"10.7759/cureus.87399","pmid":"40772215","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11653","title":"Effect of Ozempic on Diabetic Nephropathy: A Case Report.","authors":"Joseph, Jimmy","year":2025,"journal":"Cureus, 17(7), e87416","doi":"10.7759/cureus.87416","pmid":"40772213","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11654","title":"Sustained Effects of Glucagon-Like Peptide-1 (GLP-1) Agonists on Blood Pressure in Obesity and Type 2 Diabetes: A Longitudinal Case Study.","authors":"Joseph, Jimmy","year":2025,"journal":"Cureus, 17(7), e88893","doi":"10.7759/cureus.88893","pmid":"40777719","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11655","title":"The Impact of Semaglutide on Metabolic Syndrome: A Case Report.","authors":"Joseph, Jimmy","year":2025,"journal":"Cureus, 17(7), e87223","doi":"10.7759/cureus.87223","pmid":"40755669","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11656","title":"Real-world cardiovascular effects of liraglutide: transportability analysis of the LEADER trial.","authors":"Josey, Kevin; Liu, Wenhui; Warsavage, Theodore; Medici, Morten; Kvist, Kajsa; Derington, Catherine G; Reusch, Jane E B; Ghosh, Debashis; Raghavan, Sridharan","year":2025,"journal":"medRxiv : the preprint server for health sciences","doi":"10.1101/2025.05.12.25327466","pmid":"40463568","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Using transportability analysis — a statistical method that re-weights clinical trial data to match a real-world population — researchers estimated what would happen if the LEADER trial had enrolled VA veterans instead of its original participants.\n\nFor major adverse cardiovascular events (MACE): the transported hazard ratio was 0.74 (95% CI 0.61-0.90) in the VA-weighted analysis versus 0.87 (0.78-0.97) in the original LEADER trial, suggesting a 26% risk reduction in veterans compared to 13% in the trial.\n\nFor all-cause mortality: HR was 0.71 (0.57-0.89) in the VA-weighted analysis versus 0.85 (0.74-0.97) in LEADER — a 29% reduction versus 15%.\n\nThe 3-year absolute risk difference for MACE was 2.0% in the VA-weighted analysis versus 1.6% in LEADER. Results were robust across all sensitivity analyses.","whyItMatters":"US veterans are a high-risk population for cardiovascular disease — they tend to be older, have more comorbidities, and are predominantly male compared to clinical trial populations. Despite this higher risk, they've been underrepresented in GLP-1 outcome trials. This analysis provides the evidence needed to support broader GLP-1 prescribing within the VA healthcare system, potentially benefiting millions of veterans with diabetes.","specificNumbers":"","methodology":"Transportability analysis integrating data from the LEADER randomized clinical trial (n=9,336) with real-world data from 357,075 VA patients with diabetes (2015-2023). The researchers used augmented inverse probability weighting after balancing baseline characteristics between LEADER participants and trial-eligible veterans. The primary outcomes were MACE (composite of non-fatal MI, non-fatal stroke, and cardiovascular death) and all-cause mortality. Multiple sensitivity analyses varied the VA cohort composition and balancing variables.","limitations":"This is a statistical modeling study, not a new clinical trial in veterans. The analysis assumes that the treatment effect observed in LEADER can be appropriately re-weighted to the VA population, which relies on the assumption that all relevant effect modifiers are captured in the available data. The VA population is predominantly male, limiting applicability to female veterans. The study uses a preprint (medRxiv), so it has not yet undergone peer review. The approach estimates what would have happened, not what actually happened in treated VA patients."},{"rthcId":"RPEP-11657","title":"Antimicrobial Peptides Expressed by the Polyaminoglycoside Nanosystem for Bacterial Peritonitis Management via Inflammation Modulation.","authors":"Ju, Rui; Yu, Bingran; Sui, Dandan; Xu, Fu-Jian","year":2025,"journal":"Molecular pharmaceutics, 22(7), 4245-4258","doi":"10.1021/acs.molpharmaceut.5c00509","pmid":"40446212","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11658","title":"Polyaminoglycoside nanosystem expressing antimicrobial peptides for multistage chronic wound management.","authors":"Ju, Rui; Li, Yang; Sui, Dandan; Xu, Fu-Jian","year":2025,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 382, 113657","doi":"10.1016/j.jconrel.2025.113657","pmid":"40122239","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11659","title":"The Effects of Calcitonin Gene-Related Peptide on Cartilage in Osteoarthritis.","authors":"Ju, Yucan; Shen, Leyao; Huang, Qiang; Huang, Zeyu","year":2025,"journal":"International journal of rheumatic diseases, 28(7), e70357","doi":"10.1111/1756-185x.70357","pmid":"40590512","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CGRP plays an important role in OA synovial inflammation, contributing to the inflammatory cascade that damages joint tissues. However, the review also identifies CGRP's physiological roles in cartilage maintenance and potential contributions to cartilage regeneration.\n\nThe dual nature of CGRP in OA — driving inflammation while potentially supporting tissue repair — creates both challenges and opportunities for therapeutic development. The authors highlight innovative strategies for targeting CGRP to enhance cartilage regeneration rather than simply blocking the peptide entirely, as is done in migraine therapy.","whyItMatters":"Osteoarthritis is the most common joint disease worldwide and a leading cause of disability in older adults, yet there are no disease-modifying drugs — only treatments that manage symptoms. The discovery that CGRP has both harmful (inflammatory) and helpful (regenerative) effects in joints is significant because anti-CGRP drugs already exist for migraine. Understanding these dual roles is essential before repurposing migraine drugs for OA, and could lead to entirely new therapeutic strategies based on selective CGRP modulation.","specificNumbers":"","methodology":"This is a narrative review that synthesizes current evidence on CGRP's roles in osteoarthritis-affected tissues. The authors first review the fundamental physiology and pathology of CGRP in cartilage, then summarize evidence from multiple studies on CGRP in OA, and finally examine potential therapeutic strategies for targeting CGRP to promote cartilage regeneration.","limitations":"This is a narrative review that synthesizes existing literature without performing systematic analysis or meta-analysis. The evidence for CGRP's regenerative role in cartilage is still emerging and largely from preclinical studies. The optimal approach to CGRP modulation in OA (blocking vs. enhancing vs. targeted delivery) is theoretical and untested in clinical trials. The relationship between CGRP-mediated inflammation and cartilage damage may vary across different OA subtypes and disease stages."},{"rthcId":"RPEP-11660","title":"Real-World Outcomes Among Patients in the United States Receiving Tafamidis for Transthyretin Amyloid Cardiomyopathy.","authors":"Judge, Daniel P; Udall, Margarita; Rosen, Andrew M; Lamarre, Neil; Nagelhout, Elizabeth; Dao, Hanh Dung; Maurer, Mathew S","year":2025,"journal":"Cardiology and therapy","doi":"10.1007/s40119-025-00443-3","pmid":"41417197","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11661","title":"Botulinum Toxin A Modulates Keratinocyte Proliferation and Inflammatory and Pruritic Mediators in Wound Healing.","authors":"Jung, Dayeon; Shin, SunMee; Kim, Kwang Ho; Kim, Kwang Joong; Park, Eun Joo","year":2025,"journal":"Annals of dermatology, 37(5), 269-275","doi":"10.5021/ad.25.063","pmid":"41044806","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11662","title":"Glycemic Improvement with Low-Dose Dulaglutide Is Associated with Leptin and Obestatin Modulation in Type 2 Diabetes Mellitus.","authors":"Jung, Inha; Choi, Hangseok; Choi, In Young; Cho, Hyun Joo; Park, So Young; Lee, Da Young; Seo, Ji A; Kim, Nan Hee; Yu, Ji Hee","year":2025,"journal":"Diabetes & metabolism journal","doi":"10.4093/dmj.2025.0681","pmid":"41277001","tags":["dulaglutide","glp-1-agonist"],"studyType":"prospective-observational","evidenceStrength":"moderate","keyFinding":"Decreases in leptin and increases in obestatin independently predicted HbA1c reduction with dulaglutide, while changes in BMI or abdominal fat were not associated with glycemic improvement. Responders showed greater beta-cell function improvement and more pronounced food craving reductions.","whyItMatters":"Demonstrates that GLP-1 drug benefits extend beyond weight loss through hormonal modulation of leptin and obestatin, potentially enabling biomarker-based prediction of treatment response.","specificNumbers":"n=82 enrolled, 67 completed; dulaglutide 0.75 mg weekly; 24 weeks; leptin decrease and obestatin increase independently associated with HbA1c reduction","methodology":"24-week prospective observational study. 82 T2DM patients with HbA1c ≥7.0% received dulaglutide 0.75 mg weekly. Abdominal CT, food craving questionnaires, and fasting levels of leptin, adiponectin, obestatin, ghrelin, and resistin assessed at baseline and week 24. Responders defined as HbA1c reduction ≥0.5% and/or HbA1c <7.0%. Multivariable regression identified predictors of glycemic improvement.","limitations":"Single-arm, no control group; n=67 completers; low-dose only (0.75 mg); 24-week duration; observational (association not causation); 18% dropout."},{"rthcId":"RPEP-11663","title":"Semaglutide as a potential therapeutic adjunct for reducing flare-ups in Sjögren's syndrome: A case report.","authors":"Jung, John; Zazay, Ismail; Kalia, Priya; Shaghaghi, Neda; Ross, Nancy; Homan, Benjamin","year":2025,"journal":"SAGE open medical case reports, 13, 2050313X251372813","doi":"10.1177/2050313X251372813","pmid":"40900762","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11664","title":"Effect of glucagon-like peptide-1 receptor agonist on paclitaxel induced neurotoxicity in dorsal root ganglion neuronal cells in vitro.","authors":"Jung, Younghoon; Park, Seungbin; Lim, Won Yong; Hong, Jeongmin; Baik, Jiseok; Lee, Hyeon Jeong; Kwon, Jae-Young; Kim, Eunsoo","year":2025,"journal":"The Korean journal of pain, 38(3), 267-281","doi":"10.3344/kjp.24419","pmid":"40485178","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11665","title":"Treatment of obesity in spinal cord injury with tirzepatide: a case report.","authors":"Juszczak, Michael; Shem, Kazuko","year":2025,"journal":"Spinal cord series and cases, 11(1), 4","doi":"10.1038/s41394-025-00699-w","pmid":"40025019","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A male in his 40s with C6 AIS B spinal cord injury (15 years prior, BMI 32) lost 31 pounds after 3 months of tirzepatide treatment. His lipid profile improved. Prior interventions (multiple dietitians, increased physical activity) had failed to achieve weight loss. The only adverse effect was heartburn. This represents the first reported case of tirzepatide use in a spinal cord injury patient.","whyItMatters":"Approximately 300,000 Americans live with spinal cord injuries, and obesity affects the majority due to metabolic changes and exercise limitations. Cardiometabolic disease is a leading cause of death in this population. Yet SCI patients have been excluded from virtually all GLP-1 agonist and tirzepatide clinical trials. This case report provides the first evidence that tirzepatide can work safely in this underserved population, where the need for effective weight management tools is arguably greater than in the general population.","specificNumbers":"","methodology":"Single case report of a patient with chronic C6 quadriplegia and obesity treated with tirzepatide as adjunct to lifestyle interventions. Outcomes measured included body weight, BMI, lipid profile, and adverse effects over 3 months of treatment.","limitations":"Single case report (n=1) — the lowest level of clinical evidence. The 3-month follow-up is short; long-term efficacy, weight maintenance, and safety in SCI are unknown. No control comparison. The patient's specific SCI characteristics (C6, AIS B) may not represent all SCI levels and severities. The impact on SCI-specific complications (pressure injuries, respiratory function, spasticity) was not assessed. Cost and insurance coverage considerations for this population were not discussed."},{"rthcId":"RPEP-11666","title":"Multifunctionality and Possible Medical Application of the BPC 157 Peptide-Literature and Patent Review.","authors":"Józwiak, Michalina; Bauer, Marta; Kamysz, Wojciech; Kleczkowska, Patrycja","year":2025,"journal":"Pharmaceuticals (Basel, Switzerland), 18(2)","doi":"10.3390/ph18020185","pmid":"40005999","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BPC 157 has demonstrated pleiotropic beneficial effects across numerous preclinical models including tissue injury, inflammatory bowel disease, and CNS disorders. Its safety profile appears favorable with few reported side effects. However, it has not been approved by the FDA or other regulatory authorities due to the absence of sufficient human clinical studies. WADA temporarily banned it in 2022, though it is no longer on the banned list. The review also documents significant commercial and patent interest in the compound.","whyItMatters":"BPC 157 is one of the most popular peptides in the wellness and sports performance communities, widely sold online despite no regulatory approval. This review provides a needed evidence-based assessment — acknowledging the promising preclinical data while emphasizing the critical gap: no controlled human trials. For the many people already using this peptide, and for researchers, this review clarifies what is known versus assumed.","specificNumbers":"","methodology":"Literature and patent review covering the biological activities, mechanisms of action, toxicity data, and patent landscape for BPC 157.","limitations":"This is a literature review, not a clinical study. All reported therapeutic effects come from preclinical (animal) models, which may not translate to humans. The lack of randomized controlled trials in humans is the fundamental limitation — no matter how promising animal data appears. The safety profile, while favorable in preclinical models, has not been rigorously assessed in human populations."},{"rthcId":"RPEP-11667","title":"Anti-obesity compounds, Semaglutide and LiPR, and PrRP do not change the proportion of human and mouse POMC+ neurons.","authors":"Jörgensen, Sara K M; Surridge-Smith, May; Jones, Kimberley; Maletínská, Lenka; Allen, Nicholas D; Petrik, David","year":2025,"journal":"PloS one, 20(8), e0329268","doi":"10.1371/journal.pone.0329268","pmid":"40802598","tags":["semaglutide","proline-releasing-peptide","pomc"],"studyType":"in-vitro-and-animal","evidenceStrength":"low","keyFinding":"Semaglutide and lipidized prolactin-releasing peptide (LiPR) — two anti-obesity compounds — did not change the proportion of POMC-expressing neurons when applied to human stem cell-derived hypothalamic neurons or mouse brain tissue. LiPR also did not alter POMC neuron shape, gene expression patterns, or the generation of new POMC neurons in mice. This suggests anti-obesity medications do not work by rewiring the brain's appetite-suppressing neuron population.","whyItMatters":"Scientists have wondered whether weight-loss drugs like semaglutide might permanently reshape the brain's appetite circuits by changing which neurons mature into appetite-suppressing cells. This study suggests they don't — the drugs appear to work through other mechanisms rather than by altering the fundamental composition of hypothalamic neurons. This is reassuring because it means the drug effects are likely reversible rather than structural.","specificNumbers":"No change in POMC+ neuron proportion with semaglutide · No change in POMC+ neuron proportion with LiPR · No change in POMC neuron morphology · No change in metabolic gene expression","methodology":"Researchers grew hypothalamic neurons from human induced pluripotent stem cells (iPSCs) in the lab and exposed them to semaglutide or LiPR during their maturation phase. They then measured the proportion of POMC-expressing neurons. In a separate experiment, they administered LiPR to live mice and examined newly generated POMC neurons in the medial basal hypothalamus.","limitations":"This study used iPSC-derived neurons in a dish, which may not fully replicate how neurons behave in a living human brain. The mouse experiments only tested LiPR, not semaglutide. The study examined only POMC neurons and did not assess other neuron types that might be affected. Treatment duration and dosing in the lab setting may not reflect long-term clinical use."},{"rthcId":"RPEP-11668","title":"Intranasal Application of Peptides Modulating the Neuropeptide Y System.","authors":"Jülke, Eva-Maria; Özbay, Benginur; Nowicki, Marcin; Els-Heindl, Sylvia; Immig, Kerstin; Mörl, Karin; Bechmann, Ingo; Beck-Sickinger, Annette G","year":2025,"journal":"ACS pharmacology & translational science, 8(4), 1168-1181","doi":"10.1021/acsptsci.5c00082","pmid":"40242586","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11669","title":"Peptide therapeutics: current status and future opportunity with focus on nose-to-brain delivery☆.","authors":"Jülke, Eva-Maria; Beck-Sickinger, Annette G","year":2025,"journal":"Peptides, 188, 171404","doi":"10.1016/j.peptides.2025.171404","pmid":"40222598","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Over 40 peptide drugs have been approved in the last decade, targeting structures ranging from GPCRs to pathogens and treating metabolic disorders, genetic diseases, and acute illnesses. Key advances include:\n\n- Strategies to improve peptide stability: backbone modification, sequence optimization, cyclization, and addition of stabilizing moieties\n- Progress in oral peptide delivery, though requiring specialized design or GI tract permeabilization\n- Nasal administration emerging as a dual-purpose route: systemic uptake and direct nose-to-brain delivery\n- Nose-to-brain delivery already in clinical use for some compounds, though underlying mechanisms remain poorly understood\n- Peptides uniquely bridge the gap between small molecules and biologics in terms of structural diversity","whyItMatters":"Peptide therapeutics are one of the fastest-growing drug classes, driven by successes like GLP-1 agonists for diabetes and obesity. Understanding the current state of the field — including the challenges of stability, bioavailability, and delivery — is essential for appreciating where peptide medicine is heading. Nose-to-brain delivery could be transformative for neurological diseases that are currently difficult to treat.","specificNumbers":"","methodology":"This is a comprehensive review article surveying the current landscape of approved peptide therapeutics, strategies for improving peptide drug properties, and routes of administration with emphasis on nasal/nose-to-brain delivery. The review covers both approved drugs and emerging research directions.","limitations":"As a review article, this does not present new experimental data. The discussion of nose-to-brain delivery acknowledges that the underlying mechanisms are poorly understood, meaning clinical translation remains challenging. The review provides a broad overview rather than deep analysis of any single peptide drug or delivery system."},{"rthcId":"RPEP-11670","title":"Effect of once-weekly subcutaneous semaglutide on abdominal visceral fat area in Japanese adults with overweight and obesity: A post hoc analysis of the STEP 6 trial.","authors":"Kadowaki, Takashi; Nishida, Tomoyuki; Ogawa, Wataru; Overvad, Maria; Tobe, Kazuyuki; Yamauchi, Toshimasa","year":2025,"journal":"Obesity research & clinical practice, 19(2), 146-153","doi":"10.1016/j.orcp.2025.03.003","pmid":"40189961","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11671","title":"Efficacy and safety of once-weekly tirzepatide in Japanese patients with obesity disease (SURMOUNT-J): a multicentre, randomised, double-blind, placebo-controlled phase 3 trial.","authors":"Kadowaki, Takashi; Kiyosue, Arihiro; Shingaki, Tomotaka; Oura, Tomonori; Yokote, Koutaro","year":2025,"journal":"The lancet. Diabetes & endocrinology, 13(5), 384-396","doi":"10.1016/S2213-8587(24)00377-2","pmid":"40031941","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11672","title":"Oral Semaglutide in an East Asian Population With Overweight or Obesity, With or Without Type 2 Diabetes: The OASIS 2 Randomized Clinical Trial.","authors":"Kadowaki, Takashi; Heftdal, Line Dam; Ko, Hae-Jin; Overvad, Maria; Shimomura, Iichiro; Thamattoor, Usha K; Kim, Kyoung-Kon","year":2025,"journal":"JAMA internal medicine, 185(10), 1206-1217","doi":"10.1001/jamainternmed.2025.3599","pmid":"40758358","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11673","title":"Limosilactobacillus reuteri enables oral-to-systemic absorption of iberiotoxin for treatment of collagen-induced arthritis in rats.","authors":"Kady, Mohamed R; Elston, R Nicholas; Snyder, Lauren J; Fleischman, Jorie D; Brandt, Madilyn J; Zhu, Duolong; Britton, Robert A; Beeton, Christine","year":2025,"journal":"Microbial cell factories, 24(1), 177","doi":"10.1186/s12934-025-02800-2","pmid":"40753423","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Oral administration of engineered L. reuteri secreting iberiotoxin (LrIbTX) achieved comparable efficacy to injected IbTX in treating collagen-induced arthritis in rats. Both treatments significantly improved clinical joint swelling and histologic inflammation versus controls.\n\nIbTX was detected in the sera of healthy rats after oral gavage with LrIbTX, confirming systemic absorption of the intestinally-produced peptide. The oral and injected routes were also equivalent in inhibiting a delayed-type hypersensitivity reaction. No anti-IbTX antibodies were detected with either delivery method, suggesting good tolerability.","whyItMatters":"One of the biggest challenges in peptide therapeutics is oral delivery — most peptides are destroyed by stomach acid and digestive enzymes, forcing patients to rely on injections. This study demonstrates a fundamentally new approach: using engineered probiotic bacteria as living factories that produce and secrete therapeutic peptides directly in the gut, where they can be absorbed systemically. If this platform generalizes to other peptides, it could transform how peptide drugs are delivered.","specificNumbers":"","methodology":"Researchers constructed a plasmid for inducible secretion of iberiotoxin and transformed it into probiotic L. reuteri to create LrIbTX. The engineered bacteria were characterized for growth rate and fecal recovery after oral gavage. Systemic IbTX delivery was confirmed using a competitive binding assay in rat serum. Efficacy was tested in the collagen-induced arthritis (CIA) rat model, comparing oral LrIbTX to injected IbTX and control bacteria. Outcomes included clinical joint scores, histologic inflammation, bone density, anti-collagen antibodies, and anti-IbTX antibodies. A delayed-type hypersensitivity model was also used.","limitations":"This is a preclinical study in rats, and oral-to-systemic peptide delivery through engineered bacteria faces significant challenges in translation to humans, including differences in gut physiology, immune responses, and regulatory hurdles for live biotherapeutics. The specific serum levels of IbTX achieved were not quantified with standard pharmacokinetic methods. Long-term safety of chronically administering engineered bacteria that produce bioactive peptides in the gut is unknown. The collagen-induced arthritis model, while standard, does not fully recapitulate human rheumatoid arthritis."},{"rthcId":"RPEP-11674","title":"Deciphering the Neuroprotective Action of Bee Venom Peptide Melittin: Insights into Mechanistic Interplay.","authors":"Kadyan, Pankaj; Singh, Lovedeep","year":2025,"journal":"Molecular neurobiology, 62(7), 8738-8751","doi":"10.1007/s12035-025-04808-6","pmid":"40038194","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11675","title":"Transient ligand contacts of the intrinsically disordered N-terminus of neuropeptide Y2 receptor regulate arrestin-3 recruitment.","authors":"Kaiser, Anette; Rojas Echeverri, Juan C; Baischew, Asat; Pankonin, Maik; Leitner, Karl D; Iacobucci, Claudio; Sala, Davide; Ihling, Christian; Müller, Ronny; Ferenc, Rok; Beck-Sickinger, Annette G; Schmidt, Peter; Meiler, Jens; Hildebrand, Peter W; Sinz, Andrea","year":2025,"journal":"Nature communications, 16(1), 8326","doi":"10.1038/s41467-025-64051-4","pmid":"40973726","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Cross-linking mass spectrometry captured 40 contact points between a photo-reactive NPY analog and the intrinsically disordered N-terminus (NT) of the Y2 receptor. Molecular dynamics simulations revealed that these contacts are rapid and transient, with the structurally flexible NT constantly interconverting between conformations.\n\nMutagenesis of electrostatic hotspots in the NT showed that these residues control the conformational ensemble of the disordered region. Functionally, the transient NT-NPY contacts prolong ligand residence time at the receptor, which is specifically required for efficient recruitment of arrestin-3 but not for Gi protein coupling. This establishes a mechanism by which the disordered N-terminus selectively biases receptor signaling toward arrestin pathways.","whyItMatters":"Most drug design targeting GPCRs focuses on the transmembrane binding pocket, ignoring the flexible N-terminus. This study shows that the disordered tail is not just structural decoration — it actively controls which signaling pathways are activated. This has major implications for designing 'biased' peptide drugs that selectively activate beneficial pathways (like G protein signaling) while avoiding problematic ones (like arrestin-mediated desensitization), potentially leading to more effective peptide therapeutics with fewer side effects.","specificNumbers":"","methodology":"Researchers used a photo-reactive NPY analogue combined with cross-linking mass spectrometry (XL-MS) to capture transient interactions between NPY and the Y2R N-terminus that are invisible to conventional structural methods. The resulting 40 cross-links provided distance constraints for building structural models. Molecular dynamics simulations explored the conformational dynamics of the interaction. Site-directed mutagenesis of key Y2R residues, followed by functional assays for Gi protein and arrestin-3 recruitment, established the signaling consequences of disrupting NT-ligand contacts.","limitations":"The study was conducted primarily in vitro and in silico, without in vivo validation of the functional consequences. Cross-linking mass spectrometry captures snapshots of interactions that may not fully represent the dynamic reality. The mutagenesis experiments alter the receptor permanently, which differs from the transient modulation that might occur naturally. The findings are specific to the Y2R-NPY interaction and may not generalize to all peptide GPCRs, though the authors propose this as a broader mechanism."},{"rthcId":"RPEP-11676","title":"Amplifying and ameliorating light avoidance in mice with photoreceptor targeting and CGRP sensitization.","authors":"Kaiser, Eric A; Cavanah, Audrey; Aguirre, Geoffrey K; Jensen, Frances E","year":2025,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2025.05.24.655946","pmid":"40502117","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11677","title":"Bimagrumab: Novel Medical Therapy for Inclusion Body Myositis, Sarcopenia, and Medication-Induced Lean Body Mass Loss.","authors":"Kaiser, Michael; Parikh, Manish A; Turitto, Gioia; Frishman, William H; Peterson, Stephen J","year":2025,"journal":"Cardiology in review","doi":"10.1097/CRD.0000000000001113","pmid":"41248895","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11678","title":"Assessing the Occurrence of Hypertension in Patients Receiving Calcitonin Gene-Related Peptide Monoclonal Antibodies for Episodic and Chronic Migraine: A Systematic Review.","authors":"Kakde, Shradha P; Islam, Khurram; Ali, Muhammad Faizan; Anwar, Muhammad Shakaib; Nadeem, Laiba; Rana, Abdul Rauf; Rana, Abdul Wahab; Hayat, Sardar Khizar; Ali, Syed Momin; Kolanu, Nikhil Deep","year":2025,"journal":"Cureus, 17(8), e90244","doi":"10.7759/cureus.90244","pmid":"40959372","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11679","title":"Clinical features modifying the cardiovascular benefits of GLP-1 receptor agonists: a systematic review and meta-analysis.","authors":"Kalayci, Arzu; Januzzi, James Louis; Mitsunami, Makiko; Tanboga, Ibrahim Halil; Karabay, Can Yucel; Gibson, Charles Michael","year":2025,"journal":"European heart journal. Cardiovascular pharmacotherapy, 11(6), 552-561","doi":"10.1093/ehjcvp/pvaf037","pmid":"40886073","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11680","title":"Changes in natriuretic peptide levels following patiromer-enabled optimization of medical therapy in heart failure: A post hoc analysis of the DIAMOND study.","authors":"Kalogeropoulos, Andreas P; Hameed, Ishaque; Anker, Stefan D; Bayes-Genis, Antoni; Böhm, Michael; Budden, Jeffrey; Cleland, John G F; Coats, Andrew J S; Ezekowitz, Justin A; Filippatos, Gerasimos; Goudev, Assen; Khan, Muhammad Shahzeb; Lindenfeld, Joann; Lund, Lars H; Merkely, Bela; Mentz, Robert J; Metra, Marco; Moutchia, Jude; Perrin, Amandine; Ponikowski, Piotr; Priest, Elisa L; Rossignol, Patrick; Senni, Michele; Shaver, Courtney; Waechter, Sandra; Weir, Matthew R; Pitt, Bertram; Butler, Javed","year":2025,"journal":"European journal of heart failure, 27(12), 2816-2824","doi":"10.1002/ejhf.3754","pmid":"40607983","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11681","title":"Pharmacosimilars In Obesity Medicine: Informed Choice, Appropriate Choice.","authors":"Kalra, Sanjay; Singh, Amandeep; Kapoor, Nitin","year":2025,"journal":"JPMA. The Journal of the Pakistan Medical Association, 75(8), 1293-1295","doi":"10.47391/JPMA.25-61","pmid":"40851146","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11682","title":"The Peptide Paradox in Pharmacology of Obesity.","authors":"Kalra, Sanjay; Singh, Amandeep; Kapoor, Nitin","year":2025,"journal":"JPMA. The Journal of the Pakistan Medical Association, 75(7), 1138-1140","doi":"10.47391/JPMA.25-53","pmid":"40751630","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11683","title":"Peri-Procedural Safety of GLP-1 Receptor Agonists in Elective Endoscopy: A Multicenter Retrospective Cohort Study.","authors":"Kalsi, Harsimran; Bassi, Raghav; Noureldine, Hussein; Essilfie-Quaye, Kobina; Creamer, Carson; Abuassi, Mohammad; Meadows, Robyn; Brar, Tony S; Perbtani, Yaseen","year":2025,"journal":"Journal of clinical medicine, 14(17)","doi":"10.3390/jcm14176147","pmid":"40943907","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11684","title":"Semaglutide-Induced Liver Injury.","authors":"Kalsi, Harsimran; Arora, Samneet Singh; Essilfie-Quaye, Kobina; Bassi, Raghav; Akhavan, Neeka; Perbtani, Yaseen; Brar, Tony S","year":2025,"journal":"ACG case reports journal, 12(8), e01776","doi":"10.14309/crj.0000000000001776","pmid":"40761336","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A 44-year-old woman developed drug-induced liver injury (DILI) after semaglutide initiation for weight management. The causal relationship was confirmed by a positive dechallenge-rechallenge pattern: liver enzymes normalized after discontinuation and elevated again when semaglutide was restarted.\n\nThe authors conducted a literature review of all reported semaglutide-related DILI cases, finding that hepatotoxicity from semaglutide, while exceedingly rare, is a documented adverse effect that warrants clinical awareness.","whyItMatters":"Semaglutide (Ozempic/Wegovy) is one of the most widely prescribed medications in the world, with millions of users for diabetes and weight management. While liver injury is rare, the enormous and rapidly growing user base means even uncommon side effects can affect many people. This case reinforces the importance of liver monitoring and raises awareness among prescribers.","specificNumbers":"","methodology":"Single patient case report with literature review. The case involved clinical documentation of liver enzyme changes correlated with semaglutide initiation, discontinuation, and rechallenge. The accompanying literature review surveyed all previously published cases of semaglutide-induced liver injury.","limitations":"This is a single case report, the lowest level of clinical evidence. Individual case reports cannot establish incidence rates or risk factors. Other potential causes of liver injury may not have been completely excluded despite the positive rechallenge. The literature review scope and methodology are not detailed in the abstract."},{"rthcId":"RPEP-11685","title":"Advancing personalized immunotherapy for melanoma: Integrating immunoinformatics in multi-epitope vaccine development, neoantigen identification via NGS, and immune simulation evaluation.","authors":"Kamali, Mohammad Javad; Salehi, Mohammad; Fath, Mohsen Karami","year":2025,"journal":"Computers in biology and medicine, 188, 109885","doi":"10.1016/j.compbiomed.2025.109885","pmid":"40010174","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11686","title":"Evaluation of safety of preoperative GLP-1 receptor agonists in patients undergoing elective surgery: a systematic review, meta-analysis and meta-regression.","authors":"Kamarajah, Sivesh K; Gudiozzi, Nadia; Findlay, John M; Lee, Matthew J; Pinkney, Thomas; Markar, Sheraz R","year":2025,"journal":"EClinicalMedicine, 87, 103408","doi":"10.1016/j.eclinm.2025.103408","pmid":"41054439","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 97,059 patients across 21 studies (30,981 received preoperative GLP-1RA), postoperative complications showed no increased risk in GLP-1 users (pooled OR: 0.78, 95% CI: 0.59-1.05). Bayesian meta-analysis confirmed this (posterior mean OR: 0.78, 95% credible interval: 0.57-1.12). Meta-regression found no significant effect modifiers. Preoperative weight loss of up to 16.7 kg or 6.0 kg/m² was reported over six months. Overall GRADE certainty of evidence was very low due to observational designs and high heterogeneity (I²=73%).","whyItMatters":"Anesthesiologists have raised concerns about GLP-1 drugs delaying gastric emptying, potentially increasing aspiration risk during surgery. Some guidelines have recommended holding these drugs before elective procedures. This comprehensive meta-analysis — the largest to date — provides evidence that preoperative GLP-1RA use does not increase overall surgical complications, which could change perioperative management guidelines and support continued or initiated GLP-1RA use for surgical optimization.","specificNumbers":"","methodology":"Systematic review and meta-analysis (PROSPERO registered) searching PubMed, MEDLINE, Embase, and Cochrane Library through March 2025. 21 studies meeting inclusion criteria were analyzed using both frequentist and Bayesian random-effects meta-analyses. Primary outcome was 90-day perioperative complications; secondary outcome was preoperative weight loss. GRADE assessment evaluated evidence certainty. Bayesian hierarchical meta-regression explored effect modifiers.","limitations":"All 21 studies were observational — no randomized trials exist. The GRADE certainty was very low. High heterogeneity (I²=73%) suggests substantial variability across studies that meta-regression could not explain. Most studies were single-center from high-income countries, limiting generalizability. The specific concern about aspiration risk during anesthesia was not separately assessed. Publication bias cannot be excluded. The pooled OR of 0.78 did not reach statistical significance."},{"rthcId":"RPEP-11687","title":"Role of Incretin Mimetics in Cardiovascular Outcomes and Other Classical Cardiovascular Risk Factors beyond Obesity and Diabetes Mellitus in Nondiabetic Adults with Obesity: a Meta-analysis of Randomized Controlled Trials.","authors":"Kamarullah, William; Pranata, Raymond; Wiramihardja, Siska; Tiksnadi, Badai Bhatara","year":2025,"journal":"American journal of cardiovascular drugs : drugs, devices, and other interventions, 25(2), 203-229","doi":"10.1007/s40256-024-00695-9","pmid":"39616304","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11688","title":"Peptides in wound healing: A comprehensive review of their roles, challenges, and hydrogel-based delivery systems.","authors":"Kamil, Rafl M; Nyamathulla, Shaik; Mahmood, Syed","year":2025,"journal":"EXCLI journal, 24, 1657-1689","doi":"10.17179/excli2025-8778","pmid":"41584510","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11689","title":"Tear fluid calcitonin gene-related peptide (CGRP) is elevated during spontaneous migraine attacks - results from a pilot study.","authors":"Kamm, Katharina; Brandi-Dohrn, Annika; Straube, Andreas; Förderreuther, Stefanie; Ruscheweyh, Ruth","year":2025,"journal":"The journal of headache and pain, 27(1), 31","doi":"10.1186/s10194-025-02255-1","pmid":"41449339","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11690","title":"Tear fluid CGRP rises during glyceryl trinitrate-induced headache in migraine patients.","authors":"Kamm, Katharina; Khorsandian, Marie-Christine; Straube, Andreas; Ruscheweyh, Ruth","year":2025,"journal":"The journal of headache and pain, 26(1), 260","doi":"10.1186/s10194-025-02141-w","pmid":"41239208","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11691","title":"Life-Threatening Ventricular Fibrillation Linked to High-Dose Tirzepatide-Induced Gastrointestinal Side Effects.","authors":"Kammaripalle, Thirumala Keerthi Chandrika; Giordano, Jacob R; Rana, Humza; Gade, Amulya; Reddy, Sirisha","year":2025,"journal":"Cureus, 17(6), e85366","doi":"10.7759/cureus.85366","pmid":"40621252","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11692","title":"Longitudinal Evaluation of Vitamin D, Parathyroid Hormone, Antimicrobial Peptides, and Immunomodulatory Genes in Hospitalized Foals.","authors":"Kamr, Ahmed M; Bartish, Celine; Summers, Jamie; Horton, Julia; Hostnik, Laura D; Orr, Kindra; Browne, Nimet; Dembek, Katarzyna A; Saliba, Caroline; Gomez, Diego E; Toribio, Ramiro E","year":2025,"journal":"Journal of veterinary internal medicine, 39(2), e70012","doi":"10.1111/jvim.70012","pmid":"40008921","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Serum 25(OH)D, 1,25(OH)₂D, vitamin D binding protein, β-defensin-1, and cathelicidin-1 concentrations were all significantly lower in hospitalized foals compared to healthy foals at multiple time points over 72 hours (p<0.05). Parathyroid hormone (PTH) was significantly higher in sick foals.\n\nSeptic foals showed decreased expression of vitamin D receptor (VDR) and CYP27B1 (the enzyme that activates vitamin D) genes, while pro-inflammatory genes TLR-4, TNF-α, and IL-1β were upregulated. Decreased serum 25(OH)D, β-defensin-1, cathelicidin-1, and elevated PTH were each independently associated with higher odds of death in hospitalized foals (p<0.05).","whyItMatters":"The vitamin D–antimicrobial peptide axis is a fundamental innate immune pathway conserved across mammals. While this study was conducted in foals, the same pathway operates in human newborns — low vitamin D in neonatal intensive care patients is also associated with higher infection rates and worse outcomes. These findings reinforce the biological importance of vitamin D in supporting antimicrobial peptide production and innate immunity during the critical neonatal period, with potential translational implications for both veterinary and human medicine.","specificNumbers":"","methodology":"This was a longitudinal observational study of 109 foals aged 72 hours or younger, divided into hospitalized (83 foals: 60 septic, 23 sick non-septic) and healthy (26 foals) groups. Blood samples were collected at admission and at 24, 48, and 72 hours. Researchers measured serum concentrations of vitamin D metabolites, vitamin D binding protein, PTH, β-defensin-1, and cathelicidin-1. Gene expression of VDR, CYP27B1, CYP24A1, TLR-4, TNF-α, and IL-1β was assessed from white blood cells. Data were analyzed using repeated measures statistical methods.","limitations":"This is an observational study that demonstrates association, not causation — it cannot prove that low vitamin D or antimicrobial peptide levels directly cause death. The study was conducted in horses, and direct extrapolation to human neonates requires caution despite shared biology. The sample size of 109 foals with subgroups (septic, sick non-septic, healthy) limits statistical power for multivariate analyses. Whether vitamin D supplementation would improve antimicrobial peptide levels and outcomes was not tested."},{"rthcId":"RPEP-11693","title":"Once-Weekly Tirzepatide Versus Once-Daily Basal Insulin in Managing Type 2 Diabetes Inadequately Controlled With Oral anti-Hyperglycemic Drugs: A Systematic Review and Meta-Analysis.","authors":"Kamrul-Hasan, A B M; Selim, Shahjada; Afsana, Faria; Nagendra, Lakshmi; Ahmed, Rezwana; Dutta, Deep","year":2025,"journal":"Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists, 31(3), 315-325","doi":"10.1016/j.eprac.2024.12.005","pmid":"39672540","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11694","title":"Tirzepatide and Cancer Risk in Individuals with and without Diabetes: A Systematic Review and Meta-Analysis.","authors":"Kamrul-Hasan, A B M; Alam, Muhammad Shah; Dutta, Deep; Sasikanth, Thanikai; Aalpona, Fatema Tuz Zahura; Nagendra, Lakshmi","year":2025,"journal":"Endocrinology and metabolism (Seoul, Korea), 40(1), 112-124","doi":"10.3803/EnM.2024.2164","pmid":"39814031","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Over 26-72 weeks across 13 RCTs with 13,761 participants, tirzepatide showed identical cancer risk to pooled controls (RR 0.78; 95% CI: 0.53-1.16; P=0.22). Risk was comparable in patients with and without diabetes. Subgroup analyses showed no difference versus placebo, insulin, or GLP-1 receptor agonists. Only the 10 mg dose showed a lower risk of any cancer versus placebo. Despite elevated serum calcitonin with 10 mg and 15 mg doses, no papillary thyroid carcinoma cases were reported in any trial. No specific cancer type showed increased risk with tirzepatide.","whyItMatters":"GLP-1 and GIP receptor agonists like tirzepatide stimulate pathways that theoretically could promote cell growth, raising questions about cancer safety — particularly thyroid cancer, given that rodent studies with GLP-1 drugs showed thyroid tumors. This comprehensive meta-analysis of all available RCT data provides the strongest evidence to date that tirzepatide does not increase cancer risk over the study periods evaluated, which is reassuring for the millions of patients taking this drug.","specificNumbers":"","methodology":"Systematic review and meta-analysis of 13 randomized controlled trials from electronic databases. The primary outcome was overall cancer risk; secondary outcomes were specific cancer types. Tirzepatide groups were compared against pooled controls (placebo, insulin, GLP-1 agonists) and against each comparator separately. Dose-stratified subgroup analyses were performed. Study duration ranged from 26 to 72 weeks.","limitations":"The maximum follow-up was only 72 weeks, which is too short to detect cancers with long latency periods. Cancer was not the primary endpoint of the included trials, so detection may be incomplete. The total number of cancer events was small, limiting statistical power to detect modest risk increases or differences in rare cancer types. Post-marketing surveillance with longer follow-up is needed to confirm these findings."},{"rthcId":"RPEP-11695","title":"Renal effects and safety of tirzepatide in subjects with and without diabetes: A systematic review and meta-analysis.","authors":"Kamrul-Hasan, Abm; Patra, Shinjan; Dutta, Deep; Nagendra, Lakshmi; Muntahi-Reza, Afm; Borozan, Sanja; Pappachan, Joseph M","year":2025,"journal":"World journal of diabetes, 16(2), 101282","doi":"10.4239/wjd.v16.i2.101282","pmid":"39959269","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tirzepatide 10 mg reduced UACR by 26.95% more than placebo (p<0.05) and 15 mg reduced it by a similar significant margin (p=0.0008) over 26-72 weeks. All tirzepatide doses outperformed insulin for UACR reduction. The benefit was greater in type 2 diabetes patients (MD -33.25%) than in obese patients without diabetes (MD -7.93%, p=0.001 for difference).\n\neGFR was comparable across all tirzepatide doses versus insulin (no statistically significant differences). Tirzepatide showed no increased risk of adverse renal events, UTI, nephrolithiasis, acute kidney injury, or renal cancer compared to placebo, insulin, or GLP-1 receptor agonists.","whyItMatters":"Kidney disease is one of the most devastating complications of diabetes, eventually requiring dialysis or transplant. GLP-1 agonists like semaglutide have shown some kidney benefits, and this meta-analysis provides the first comprehensive evidence that tirzepatide (which targets both GLP-1 and GIP receptors) also protects the kidneys. Since tirzepatide is rapidly becoming one of the most prescribed drugs worldwide, confirming its kidney safety and potential benefits is critical for the millions of patients taking it.","specificNumbers":"","methodology":"Systematic review and meta-analysis of 15 randomized controlled trials (n=14,471) identified from multiple electronic databases. Trials compared tirzepatide to placebo, insulin, or GLP-1 RAs in patients with type 2 diabetes or obesity. Primary outcomes: percent change from baseline in UACR and absolute change in eGFR. Secondary outcome: renal safety events. Random-effects models were used. Most included studies had low risk of bias.","limitations":"Follow-up was only 26-72 weeks — too short to see hard kidney endpoints like eGFR decline, dialysis, or renal death. UACR reduction is a surrogate marker; whether it translates to actual kidney disease prevention requires longer trials. The greater UACR benefit in diabetes vs. obesity-only patients may reflect higher baseline albuminuria rather than differential drug effect. The dedicated kidney outcomes trial (TRANSCEND) is needed for definitive evidence."},{"rthcId":"RPEP-11696","title":"Role of Sodium-Glucose Cotransporter-2 Inhibitors in Managing Polycystic Ovary Syndrome: A Systematic Review.","authors":"Kamrul-Hasan, Abm; Mondal, Sunetra; Zahura Aalpona, Fatema Tuz; Nagendra, Lakshmi; Dutta, Deep","year":2025,"journal":"TouchREVIEWS in endocrinology, 21(1), 32-41","doi":"10.17925/EE.2025.21.1.2","pmid":"40485656","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across five RCTs studying canagliflozin, empagliflozin, dapagliflozin, and licogliflozin in 269 overweight/obese PCOS patients, SGLT2 inhibitors reduced insulin resistance (lower HOMA-IR, insulin, and fasting glucose), decreased body weight, BMI, waist circumference, and total body fat, and lowered triglycerides. DHEAS levels decreased in two trials, though total testosterone and free androgen index generally did not change.\n\nNotably, the combination of SGLT2i with a GLP-1 receptor agonist produced the most prominent improvements in body composition and metabolic parameters, while SGLT2i combined with metformin showed better effects on hormonal parameters. Menstrual irregularity and hirsutism scores improved. LDL cholesterol slightly increased in most trials. Adverse effects were mostly mild genital infections.","whyItMatters":"PCOS is the most common hormonal disorder in women of reproductive age, affecting 6-12% worldwide. Current treatments are limited and often address only individual symptoms. SGLT2 inhibitors target the underlying insulin resistance that drives much of PCOS pathology. The finding that combining SGLT2i with GLP-1 drugs produces superior metabolic improvements could establish a new combination therapy paradigm for PCOS that addresses the metabolic root cause rather than just managing symptoms.","specificNumbers":"","methodology":"Systematic review of randomized controlled trials identified through electronic database searches. Inclusion criteria: RCTs of overweight/obese PCOS patients receiving SGLT2 inhibitors versus placebo or non-hormonal active comparators. Five trials with 269 participants were included. Outcomes assessed included metabolic parameters (insulin resistance, glucose, lipids), hormonal markers (testosterone, DHEAS), anthropometric measures (weight, BMI, waist), body composition, and clinical features (menstrual regularity, hirsutism).","limitations":"Only 5 RCTs with 269 total participants were available, providing limited statistical power. The studies used different SGLT2 inhibitors at different doses, limiting comparability. Follow-up durations were relatively short. No meta-analysis was performed (systematic review only). The GLP-1 RA combination data came from limited studies. Long-term effects on fertility, pregnancy outcomes, and cardiovascular risk were not assessed. SGLT2 inhibitors are not approved for PCOS, so all use is off-label."},{"rthcId":"RPEP-11697","title":"Reasons for discontinuing tirzepatide in randomized controlled trials: A systematic review and meta-analysis.","authors":"Kamrul-Hasan, Abul Bashar Mohammad; Pappachan, Joseph M; Dutta, Deep; Nagendra, Lakshmi; Kuchay, Mohammad Shafi; Kapoor, Nitin","year":2025,"journal":"World journal of diabetes, 16(4), 101731","doi":"10.4239/wjd.v16.i4.101731","pmid":"40236848","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11698","title":"Safety and efficacy of glucagon-like peptide-1 receptor agonists in individuals with type 2 diabetes mellitus fasting during Ramadan: a systematic review and meta-analysis.","authors":"Kamrul-Hasan, Abul Bashar Mohammad; Pappachan, Joseph M; Ashraf, Hamid; Nagendra, Lakshmi; Dutta, Deep; Kuchay, Mohammad Shafi; Shaikh, Shehla","year":2025,"journal":"World journal of methodology, 15(4), 105478","doi":"10.5662/wjm.v15.i4.105478","pmid":"40900863","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11699","title":"The impact of semaglutide on liver outcomes in patients with or at risk of MASH: a dose and duration response meta-analysis of randomized trials.","authors":"Kan, Ranran; Wang, Siyi; Meng, Xiaoyu; Guo, Yaming; Li, Danpei; Yu, Xuefeng","year":2025,"journal":"Diabetology & metabolic syndrome, 17(1), 439","doi":"10.1186/s13098-025-01995-z","pmid":"41286982","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 22 RCTs and 32,013 patients:\n\n- MASH Resolution: significantly improved (RR 1.98, 95% CI: 1.57-2.50) — nearly doubling the resolution rate\n- Fibrosis Regression: NOT significantly improved (RR 1.18, 95% CI: 0.74-1.88)\n- Liver Steatosis: reduced by 11.3% (95% CI: -18.70 to -3.91)\n- ELF score (fibrosis marker): reduced by 0.49 (95% CI: -0.70 to -0.29)\n- ALT: reduced by 5.55 U/L; AST: reduced by 3.85 U/L\n- All-cause mortality: reduced 18% (RR 0.82, 95% CI: 0.74-0.91)\n- Cardiovascular risk: reduced 17% (RR 0.83, 95% CI: 0.75-0.92)\n- Best results at doses ≥2.0 mg weekly and durations ≥12 months","whyItMatters":"MASH is expected to become the leading cause of liver transplantation worldwide, and until recently there were almost no approved pharmacotherapies. Semaglutide's ability to resolve MASH in nearly twice as many patients as placebo is clinically significant. However, the failure to improve fibrosis — the key driver of cirrhosis, liver failure, and death — is an important limitation that must temper enthusiasm. The mortality and cardiovascular benefits add independent value, but for patients with advanced fibrosis, semaglutide alone may not be sufficient.","specificNumbers":"","methodology":"Systematic search of PubMed, Embase, Cochrane Library, and ClinicalTrials.gov through August 2025 for randomized controlled trials of semaglutide in MASH patients. Twenty-two RCTs with 32,013 patients were included. PRISMA guidelines were followed. Outcomes included MASH resolution, fibrosis regression, liver steatosis, ELF score, liver enzymes (ALT, AST), weight, glycemic and lipid parameters, all-cause mortality, and cardiovascular risk. Subgroup analyses assessed dose-response (dose ≥2.0 mg vs. lower) and duration-response (≥12 months vs. shorter) relationships.","limitations":"The 22 included RCTs likely varied in patient populations, semaglutide formulations (subcutaneous vs. oral), doses, and MASH severity, introducing heterogeneity. The fibrosis outcome was not statistically significant, but the confidence interval was wide (0.74-1.88), suggesting the analysis may have been underpowered for this endpoint. Many included trials may have enrolled patients based on metabolic criteria rather than biopsy-confirmed MASH. The mortality and cardiovascular benefits come largely from cardiovascular outcomes trials that included MASH as a secondary population, not from MASH-specific trials."},{"rthcId":"RPEP-11700","title":"Effect of Vosoritide therapy on IGF-I and Endogenous C-type Natriuretic Peptide in Hypochondroplasia.","authors":"Kanakatti Shankar, Roopa; Galetaki, Despoina M; Zhang, Anqing; Shafaei, Niusha; Pitner, Kimberly; Seaforth, Raheem; Prickett, Tim; Espiner, Eric; Dauber, Andrew","year":2025,"journal":"The Journal of clinical endocrinology and metabolism","doi":"10.1210/clinem/dgaf591","pmid":"41157964","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11701","title":"Impact of flour particle size and origin on the bread structure and the postprandial glycemic, insulinemic and appetite responses in healthy adults.","authors":"Kanata, Maria-Christina; Yanni, Amalia E; Koliaki, Chrysi; Anastasiou, Ioanna A; Tentolouris, Nikolaos; Karathanos, Vaios T","year":2025,"journal":"Food & function, 16(11), 4548-4561","doi":"10.1039/d5fo00348b","pmid":"40388189","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11702","title":"From pathophysiology to novel approaches for obesity-associated hypertension.","authors":"Kanbay, Mehmet; Yayci, Elif; Genc, Candan; Copur, Sidar; Aktas, Ozgur; Sarafidis, Pantelis; Covic, Adrian; Ortiz, Alberto; Laffin, Luke J","year":2025,"journal":"Clinical kidney journal, 18(8), sfaf218","doi":"10.1093/ckj/sfaf218","pmid":"40761303","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11703","title":"Glucagon and glucagon-like peptide-1 dual agonist therapy: A possible future towards fatty kidney disease.","authors":"Kanbay, Mehmet; Copur, Sidar; Guldan, Mustafa; Ozbek, Lasin; Mallamaci, Francesca; Zoccali, Carmine","year":2025,"journal":"European journal of clinical investigation, 55(1), e14330","doi":"10.1111/eci.14330","pmid":"39400355","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11704","title":"A Distinct Subpopulation of Extended Amygdala Neurons Drives Food Intake.","authors":"Kandil, Isaac F; Rogers, Ethan T; Morningstar, Allison R; Giardino, William J","year":2025,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2025.11.07.685941","pmid":"41292976","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11705","title":"Peptide Inhibitors Targeting FOXO4-p53 Interactions and Inducing Senescent Cancer Cell-specific Apoptosis.","authors":"Kang, Donghoon; Lim, Yeji; Ahn, Dabin; Lee, Jaeseok; Park, Chin-Ju","year":2025,"journal":"Journal of medicinal chemistry, 68(15), 15683-15694","doi":"10.1021/acs.jmedchem.5c00537","pmid":"40739602","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Using NMR spectroscopy, researchers identified that hydrophobic interactions in p53's transactivation domain are key to its binding with FOXO4's forkhead domain. Based on this structural insight, they designed CPP-CAND — an optimized peptide with reduced negative charges and a cationic cell-penetrating peptide for cellular delivery.\n\nCPP-CAND demonstrated:\n- High selectivity for senescent cells over non-senescent cells\n- Effective disruption of nuclear FOXO4-p53 foci (the protein complexes keeping senescent cells alive)\n- Induction of caspase-dependent apoptosis (programmed cell death)\n- Cytotoxicity against senescent cancer cells induced by both doxorubicin and cisplatin (two different chemotherapy agents)\n- Practical advantages: composed of natural L-amino acids, shorter sequence length than previous FOXO4-DRI peptide approaches","whyItMatters":"Cancer recurrence after chemotherapy is a major clinical problem, and therapy-induced senescent cells are increasingly recognized as a driver. Senolytic drugs — agents that selectively kill senescent cells — are a hot area of research for both cancer and aging. CPP-CAND represents a more targeted approach than previous FOXO4-targeting peptides, with practical advantages (natural amino acids, shorter length) that could facilitate clinical development.","specificNumbers":"","methodology":"Researchers used NMR spectroscopy to map the molecular interactions between FOXO4 and p53 at the structural level. Based on these findings, they rationally designed peptide inhibitors, optimizing for charge, cellular uptake, and selectivity. The lead candidate (CPP-CAND) was tested in cancer cell cultures for selectivity toward senescent vs. non-senescent cells, ability to disrupt FOXO4-p53 nuclear complexes, induction of apoptosis (caspase activation), and activity against cells made senescent by different chemotherapy drugs.","limitations":"This is an in vitro study using cancer cell lines. No in vivo animal experiments or human data are presented. Selectivity was demonstrated against senescent versus non-senescent cancer cells, but effects on normal senescent cells (which may have beneficial roles) are not discussed. Pharmacokinetics, stability, and potential off-target effects in living organisms are unknown. The peptide's effectiveness may vary across different cancer types and senescence-inducing conditions."},{"rthcId":"RPEP-11706","title":"Combined treatment of TKIs with Cilengitide overcomes afatinib-resistance in EGFR-mutated NSCLC cells.","authors":"Kang, Hye Eun; Seo, Yujin; Kim, Yeonsoo; Kim, Jiyeon","year":2025,"journal":"Molecular biology reports, 53(1), 233","doi":"10.1007/s11033-025-11405-2","pmid":"41460535","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11707","title":"Controlling intracellular processing to enhance spherical nucleic acid immune stimulation.","authors":"Kang, Janice; Teplensky, Michelle H; Dittmar, Jasper W; Evangelopoulos, Michael; Hwang, Jeongmin; Mirkin, Chad A","year":2025,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 122(45), e2409554122","doi":"10.1073/pnas.2409554122","pmid":"41183209","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Two ERAP1-responsive peptide linkers (EPLs) were designed to vary antigen processing efficiency by 10-fold. The more efficient EPL produced multiple downstream improvements:\n\n- Increased antigen colocalization with ERAP1 by ~58% compared to SNAs without the linker\n- Augmented antigen surface presentation by 30%\n- Boosted ex vivo CD8+ T cell proliferation fivefold\n- Increased in vivo proinflammatory CD8+ T cells by 5% and effector memory CD8+ T cells by 18%\n- Achieved 2.5-fold more effective inhibition of E.G7-OVA lymphoma tumors in vivo\n\nThese results demonstrate that rationally designed peptide linkers can spatially bias antigen processing to a specific intracellular compartment (the ER) and dramatically enhance immune stimulation from the same antigen payload.","whyItMatters":"Most vaccine design focuses on choosing the right antigen, but this study shows that the peptide linkage connecting the antigen to its delivery vehicle is equally critical. By controlling the intracellular processing pathway — essentially telling the cell which enzyme to use and how fast to work — researchers can dramatically amplify immune responses without changing the antigen. This principle could improve cancer vaccines, infectious disease vaccines, and immunotherapies across the board.","specificNumbers":"","methodology":"The researchers designed two ERAP1-responsive peptide linkers based on the substrate specificity of ERAP1, a protease that generates MHC class I epitopes in the endoplasmic reticulum. These linkers were used to attach peptide antigens to spherical nucleic acid (SNA) nanostructures. In vitro experiments measured ERAP1 colocalization, antigen surface presentation, and CD8+ T cell proliferation. In vivo testing used a C57BL/6 mouse model with E.G7-OVA lymphoma tumors to assess immune cell generation and tumor inhibition.","limitations":"The study used a model antigen (ovalbumin) in a mouse lymphoma model, which may not predict performance with clinically relevant tumor antigens in humans. Only two peptide linker designs were tested. The E.G7-OVA tumor model is well-established but represents an idealized scenario. Human ERAP1 has genetic polymorphisms that could affect processing efficiency across populations. Manufacturing complexity of multi-component SNA constructs may limit scalability."},{"rthcId":"RPEP-11708","title":"Injection-Based Therapies for Migraine in Older Adults: A Narrative Review of OnabotulinumtoxinA, Greater Occipital Nerve Block, and Anti-Calcitonin Gene-Related Peptide Monoclonal Antibodies.","authors":"Kang, Mi-Kyoung; Cho, Soohyun; Kim, Byung-Kun; Moon, Heui-Soo; Lee, Mi Ji; Kim, Soo-Kyoung; Park, Hong-Kyun; Chu, Min-Kyung; Ha, Woo-Seok; Kim, Byung-Su; Cho, Soo-Jin","year":2025,"journal":"Journal of Korean medical science, 40(38), e297","doi":"10.3346/jkms.2025.40.e297","pmid":"41025346","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11709","title":"One-Year Compliance After Calcitonin Gene-Related Peptide Monoclonal Antibody Therapy for Migraine Patients in a Real-World Setting: A Multicenter Cross-Sectional Study.","authors":"Kang, Mi-Kyoung; Sohn, Jong-Hee; Cha, Myoung-Jin; Kim, Yoo Hwan; Hong, Yooha; Im, Hee-Jin; Cho, Soo-Jin","year":2025,"journal":"Journal of clinical medicine, 14(3)","doi":"10.3390/jcm14030734","pmid":"39941406","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11710","title":"Thalamic CGRP neurons define a spinothalamic pathway for affective pain.","authors":"Kang, Sukjae J; Liu, Shijia; Kim, Jong-Hyun; Kim, Dong-Il; Oh, Tae Gyu; Peng, Jiahang; Ye, Mao; Lee, Kuo-Fen; Evans, Ronald M; Goulding, Martyn; Han, Sung","year":2025,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 122(28), e2505889122","doi":"10.1073/pnas.2505889122","pmid":"40632570","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11711","title":"Epigallocatechin gallate ameliorates oxaliplatin-induced peripheral neuropathy via upregulation of IGF-1 signaling and suppression of neuroinflammation.","authors":"Kang, Wen; Liu, Kang; Pan, Xia; le, Yue; Wang, Long","year":2025,"journal":"Neuropharmacology, 280, 110660","doi":"10.1016/j.neuropharm.2025.110660","pmid":"40882703","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11712","title":"Comparative efficacy and tolerability of currently approved incretin mimetics: A systematic analysis of placebo-controlled clinical trials.","authors":"Kang, Yu Mi; Punov, Viktoria; Lim, Soo; Nauck, Michael A","year":2025,"journal":"Diabetes, obesity & metabolism, 27(7), 3736-3746","doi":"10.1111/dom.16398","pmid":"40212008","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11713","title":"Design of peptide functionalized nitrogen doped graphene quantum dots for theranostic application in breast cancer.","authors":"Kansara, Vrushti; Patel, Mitali","year":2025,"journal":"European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 216, 114842","doi":"10.1016/j.ejpb.2025.114842","pmid":"40876603","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11714","title":"Effect of tirzepatide treatment on patient-reported outcomes among SURMOUNT-OSA participants with obstructive sleep apnea and obesity.","authors":"Kanu, Chisom; Shinde, Shraddha; Chakladar, Sujatro; Dennehy, Ellen B; Weaver, Terri E; Poon, Jiat Ling; Malhotra, Atul","year":2025,"journal":"Sleep medicine, 134, 106719","doi":"10.1016/j.sleep.2025.106719","pmid":"40774158","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"At 52 weeks, tirzepatide (10 or 15 mg) produced significantly greater improvements compared to placebo across multiple patient-reported outcome measures: PROMIS Sleep-Related Impairment, PROMIS Sleep Disturbance, Functional Outcomes of Sleep Questionnaire activity levels, EQ-5D-5L quality of life, and most domains of the SF-36 health survey.\n\nTirzepatide was also associated with greater improvements on the Patient Global Impression of Status and Change scales. In Study 1 (participants not using PAP therapy), Epworth Sleepiness Scale scores (daytime sleepiness) also improved significantly. These subjective benefits complement the previously reported objective improvements in AHI (breathing interruption frequency), hypoxic burden, and cardiovascular risk factors.","whyItMatters":"Sleep apnea affects an estimated 936 million adults worldwide, and the standard treatment — CPAP machines — has notoriously poor adherence. Tirzepatide could become the first effective pharmaceutical alternative for sleep apnea, and these patient-reported data show that the benefits extend beyond laboratory measurements to real improvements in how patients sleep, function, and feel. This makes a compelling case for a new treatment paradigm.","specificNumbers":"","methodology":"Prespecified analysis of patient-reported outcomes from SURMOUNT-OSA — two randomized, double-blind, placebo-controlled Phase 3 trials of tirzepatide (10 or 15 mg) for 52 weeks in participants with moderate-to-severe OSA and obesity. Study 1 enrolled patients not using PAP; Study 2 enrolled PAP users who withdrew PAP before assessments. Multiple validated PROMs were assessed at baseline and Week 52 using analysis of covariance.","limitations":"This is a secondary analysis of prespecified endpoints from the SURMOUNT-OSA trials — the primary endpoint (AHI reduction) was reported separately. In Study 2, PAP was withdrawn before assessment, which may have influenced results. Patient-reported outcomes are inherently subjective. The 52-week duration, while substantial, doesn't address long-term durability of benefits. The study population may not represent all sleep apnea patients."},{"rthcId":"RPEP-11715","title":"N‑Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) as a Biomarker in Heart Failure With Preserved Ejection Fraction (HFpEF) Versus Heart Failure With Reduced Ejection Fraction (HFrEF): The Way Forward in the Age of Proteomics.","authors":"Kanyal, Shweta; Das, Abhirami; Bashir, Anas M Din; Syed, Ahmed H; Aujla, Savvy; Chaudhary, Jainam; Patel, Dharmik; Goel, Ashish","year":2025,"journal":"Cureus, 17(10), e94162","doi":"10.7759/cureus.94162","pmid":"41209853","tags":[],"studyType":"Review","evidenceStrength":"moderate","keyFinding":"NT-proBNP remains the gold standard biomarker for diagnosing and assessing prognosis in heart failure, but its performance differs significantly between heart failure subtypes. In HFrEF (reduced ejection fraction), elevated NT-proBNP levels strongly correlate with the severity of ventricular dysfunction and reliably guide treatment decisions. However, in HFpEF (preserved ejection fraction), NT-proBNP's diagnostic specificity is reduced because levels are confounded by age, kidney function, and obesity — meaning doctors often need additional imaging or biomarkers to confirm the diagnosis.\n\nThe review highlights emerging proteomic biomarkers like soluble ST2 and GDF-15 that complement NT-proBNP by reflecting different molecular pathways of heart remodeling and inflammation. The authors argue that multimarker strategies combining NT-proBNP with these newer biomarkers will be necessary for precision-based heart failure management.","whyItMatters":"Heart failure affects over 37 million people worldwide, and correctly distinguishing between HFpEF and HFrEF is critical because the treatments differ. NT-proBNP is the most widely used peptide biomarker in cardiology, but its limitations in HFpEF leave a diagnostic gap. Understanding where this peptide biomarker works well and where it falls short is essential for improving heart failure care.","specificNumbers":"37+ million people affected by HF worldwide · NT-proBNP = gold standard biomarker · Diagnostic specificity reduced in HFpEF · Novel markers: soluble ST2, GDF-15","methodology":"Narrative review integrating current evidence on NT-proBNP's pathophysiology, clinical thresholds, predictive capacity across heart failure phenotypes, and emerging proteomic biomarkers. Published in Cureus.","limitations":"As a narrative review, it synthesizes existing evidence rather than presenting new data. Published in Cureus, which has a less rigorous peer review process than top-tier cardiology journals. Does not provide specific quantitative thresholds or meta-analytic data comparing biomarker performance."},{"rthcId":"RPEP-11716","title":"iDNS3IP: Identification and Characterization of HCV NS3 Protease Inhibitory Peptides.","authors":"Kao, Hui-Ju; Weng, Tzu-Hsiang; Chen, Chia-Hung; Yu, Chen-Lin; Chen, Yu-Chi; Huang, Chen-Chen; Huang, Kai-Yao; Weng, Shun-Long","year":2025,"journal":"International journal of molecular sciences, 26(11)","doi":"10.3390/ijms26115356","pmid":"40508165","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11717","title":"Real-world insights into incretin-based therapy: Associations between changes in taste perception and appetite regulation in individuals with obesity and overweight: A cross-sectional study.","authors":"Kapan, Ali; Moser, Othmar; Felsinger, Richard; Waldhoer, Thomas; Haider, Sandra","year":2025,"journal":"Diabetes, obesity & metabolism, 27(9), 5008-5018","doi":"10.1111/dom.16548","pmid":"40552449","tags":[],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"Among 411 adults on GLP-1 drugs, about 1 in 5 reported heightened taste perception — 21.3% noticed sweet foods tasted sweeter, and 22.6% noticed salty foods tasted saltier. These taste changes were significantly linked to better appetite outcomes:\n\n- Increased sweet taste perception → 2× higher odds of feeling full (AOR 2.02), 67% higher odds of reduced appetite, 85% higher odds of reduced cravings\n- Increased salty taste perception → 2.17× higher odds of feeling full\n\nAll three GLP-1 drugs showed impressive BMI reductions: Wegovy 17.6%, Ozempic 17.4%, Mounjaro 15.5%. Over 58% reported reduced appetite and 63.5% reported increased satiety.","whyItMatters":"Many GLP-1 drug users report that food 'tastes different' — but this is one of the first studies to quantify taste changes and link them to treatment outcomes. The finding that people whose taste perception changes have significantly better appetite control suggests taste alteration may be a mechanism — not just a side effect — of how these drugs work. If confirmed, taste perception could become a simple clinical marker for predicting who will respond best to GLP-1 therapy.","specificNumbers":"n=411 · Wegovy n=217, Ozempic n=148, Mounjaro n=46 · 21.3% increased sweet taste · 22.6% increased salty taste · BMI reduction: 17.6% Wegovy, 17.4% Ozempic, 15.5% Mounjaro · AOR sweet→satiety 2.02 · AOR salty→satiety 2.17 · 58.4% reduced appetite · 63.5% increased satiety","methodology":"Cross-sectional online survey of 411 adults with obesity or overweight currently taking Wegovy, Ozempic, or Mounjaro. Survey assessed sociodemographic data, anthropometric changes, taste perception changes, and appetite-related outcomes (satiety, appetite, cravings). Multivariable logistic regression adjusted for baseline BMI, treatment duration, dose, age, and sex.","limitations":"Cross-sectional design — cannot prove taste changes cause better appetite outcomes (correlation only). Self-reported data with no objective taste testing. Online survey introduces selection bias (more engaged/tech-savvy participants). No pre-treatment taste baseline. Mounjaro subgroup was small (n=46). Recall bias possible for retrospective assessment of taste changes. No placebo control group."},{"rthcId":"RPEP-11718","title":"Functional and Aesthetic Periorbital, Ocular Adnexal and Ocular Surface Changes Linked to GLP-1 Receptor Agonists.","authors":"Kapantais, Dimitrios; Tsoutsanis, Panagiotis","year":2025,"journal":"Journal of clinical medicine, 14(24)","doi":"10.3390/jcm14248792","pmid":"41464694","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11719","title":"Interactions of Laurylated and Myristoylated KR12 Fragment of the LL37 Peptide with Polyoxidovanadates.","authors":"Kapica, Martyna; Kamysz, Elżbieta; Grabowska, Ola; Tesmar, Aleksandra; Pająk, Marek; Chmur, Katarzyna; Brzeski, Jakub; Samsonov, Sergey A; Wyrzykowski, Dariusz","year":2025,"journal":"Molecules (Basel, Switzerland), 30(7)","doi":"10.3390/molecules30071589","pmid":"40286212","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"ITC and molecular dynamics simulations revealed that binding of the lipopeptides C12-KR12 and C14-KR12 to decavanadate ([V10O28]6-) is non-specific and driven primarily by enthalpic contributions from electrostatic interactions between the peptides' positively charged residues and the anionic vanadate.\n\nCircular dichroism spectroscopy showed that both lipopeptides adopt α-helical conformations at pH 5, with C14-KR12 (myristic acid conjugate) showing greater thermal stability than C12-KR12 (lauric acid conjugate). Critically, interaction with decavanadate disrupted the α-helical structure and reduced thermal stability of both peptides.","whyItMatters":"Understanding how antimicrobial peptides interact with metal-containing compounds is relevant to developing peptide-based antibiotics and understanding how environmental or therapeutic metal ions might affect peptide function. The finding that vanadium compounds disrupt the helical structure needed for antimicrobial activity has implications for using these peptides in environments where metal ions are present.","specificNumbers":"","methodology":"Three complementary techniques: (1) Isothermal titration calorimetry (ITC) determined binding stoichiometry and thermodynamic parameters (ΔG, ΔH, TΔS). (2) Circular dichroism (CD) spectroscopy assessed secondary structure and thermal stability. (3) Molecular dynamics (MD) simulations modeled peptide-vanadate interactions at the atomic level. Experiments conducted in 50 mM sodium cacodylate buffer at pH 5.","limitations":"This is a biophysical characterization study conducted under specific buffer conditions (pH 5) that may not fully represent physiological environments. The biological implications of peptide-vanadate interactions are not explored — no antimicrobial activity or cell-based experiments were performed. The relevance to in vivo antimicrobial function is unclear, as decavanadate concentrations in biological systems are very low."},{"rthcId":"RPEP-11720","title":"Bioactive Milk Peptides as a Nutraceutical Opportunity and Challenges.","authors":"Kapoor, Devesh U; Gaur, Mansi; Kumar, Akash; Ansari, Mohd Nazam; Prajapati, Bhupendra","year":2025,"journal":"Current protein & peptide science, 26(1), 41-56","doi":"10.2174/0113892037319188240806074731","pmid":"39171470","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11721","title":"Glucagon-Like Peptide 1 Receptor Agonists, Sodium-Glucose Cotransporter 2 Inhibitors, and Risk of Autoimmune Rheumatic Diseases.","authors":"Karacabeyli, Derin; Lacaille, Diane; Lu, Na; Xie, Hui; Aviña-Zubieta, J Antonio","year":2025,"journal":"Arthritis & rheumatology (Hoboken, N.J.)","doi":"10.1002/art.70044","pmid":"41466578","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11722","title":"Glucagon-like peptide-1 receptor agonists in arthritis: current insights and future directions.","authors":"Karacabeyli, Derin; Lacaille, Diane","year":2025,"journal":"Nature reviews. Rheumatology, 21(11), 671-683","doi":"10.1038/s41584-025-01302-0","pmid":"41034339","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In vitro and preclinical in vivo experiments revealed weight-loss-independent anti-inflammatory and chondroprotective (cartilage-protecting) properties of GLP-1 RAs in arthritis models. Clinical data for knee osteoarthritis suggests GLP-1 RAs improve pain and function and reduce the risk of surgical intervention, though effects on OA incidence are incompletely understood.\n\nFor gout, GLP-1 RAs do not directly prevent attacks but effectively manage the cardiometabolic conditions commonly associated with gout. Evidence for effects on incidence, disease activity, and progression of rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis remains limited and requires further research.","whyItMatters":"One in six adults is obese, and obesity worsens arthritis while increasing cardiovascular death risk — the leading killer of arthritis patients. GLP-1 drugs addressing weight, cardiovascular risk, and potentially joint inflammation simultaneously could be transformative for millions of arthritis patients. The discovery of direct anti-inflammatory effects independent of weight loss is particularly significant.","specificNumbers":"","methodology":"Comprehensive narrative review published in Nature Reviews Rheumatology examining in vitro, preclinical, and clinical evidence for GLP-1 RA effects across multiple arthritis types: osteoarthritis, gout, rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis.","limitations":"Clinical evidence is strongest for osteoarthritis and weaker for inflammatory arthritides (RA, PsA, axSpA). The weight-loss-independent anti-inflammatory effects are mainly from preclinical studies. It's difficult to separate direct drug effects from weight loss benefits in clinical settings. GLP-1 RAs are not currently approved for any arthritis indication."},{"rthcId":"RPEP-11723","title":"Effect of glucagon-like peptide-1 receptor agonists and co-agonists on body composition: Systematic review and network meta-analysis.","authors":"Karakasis, Paschalis; Patoulias, Dimitrios; Fragakis, Nikolaos; Mantzoros, Christos S","year":2025,"journal":"Metabolism: clinical and experimental, 164, 156113","doi":"10.1016/j.metabol.2024.156113","pmid":"39719170","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11724","title":"GLP-1 Receptor Agonists and Myocardial Perfusion: Bridging Mechanisms to Clinical Outcomes.","authors":"Karakasis, Paschalis; Patoulias, Dimitrios; Theofilis, Panagiotis; Pamporis, Konstantinos; Sagris, Marios; Vlachakis, Panayotis K; Koufakis, Theocharis; Antoniadis, Antonios P; Fragakis, Nikolaos","year":2025,"journal":"International journal of molecular sciences, 26(7)","doi":"10.3390/ijms26073050","pmid":"40243679","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review summarizes evidence that GLP-1R activation improves coronary microvascular function through multiple mechanisms:\n\n- Improved endothelial function in coronary microvasculature\n- Increased nitric oxide bioavailability\n- Attenuation of oxidative stress\n- Reduced vascular inflammation\n- Improved myocardial blood flow and myocardial perfusion reserve\n- Enhanced coronary endothelial function, particularly in high-risk populations with T2D\n- Benefits extend beyond glycemic control to direct cardiovascular effects\n- Inconsistencies across studies due to variability in populations, designs, and imaging methods","whyItMatters":"Coronary microvascular dysfunction affects millions of people, especially those with diabetes, but has no specific approved treatment. If GLP-1 drugs can improve microvascular blood flow to the heart, this could explain part of their cardiovascular benefit and position them as targeted therapy for a currently undertreated condition.","specificNumbers":"","methodology":"This is a narrative review synthesizing preclinical and clinical evidence on GLP-1 receptor agonists' effects on coronary microvascular function. The review covers molecular mechanisms, animal model data, and clinical imaging studies of myocardial perfusion in patients treated with GLP-1 drugs.","limitations":"As a narrative review, no original data is presented. The evidence base includes both preclinical and clinical studies of varying quality. Inconsistencies across studies make definitive conclusions difficult. Most clinical studies were relatively small, and imaging methodologies for assessing microvascular function vary. Large-scale trials specifically designed to test GLP-1 effects on coronary microcirculation are lacking."},{"rthcId":"RPEP-11725","title":"Effect of Semaglutide on Insulin Dose Reduction in Adults With Type 1 Diabetes and Obesity Using Automated Insulin Delivery Systems: ADJUST-T1D Post Hoc Analysis.","authors":"Karakus, Kagan E; Akturk, Halis K; Kruger, Davida; Ahmann, Andrew; Bharvaga, Anuj; Langel, Christine R; Ackeifi, Courtney A; Rosen, Jonathan; Pyle, Laura; Snell-Bergeon, Janet K; Shah, Viral N","year":2025,"journal":"Diabetes care","doi":"10.2337/dc25-2249","pmid":"41429002","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Over 26 weeks, semaglutide produced a 22.6% reduction in total daily insulin dose (95% CI: -28.3 to -17.0), driven by a 30.5% reduction in bolus insulin and 15.6% reduction in basal insulin. The basal/TDD ratio increased from 0.56 to 0.62. Insulin dose decreased from 0.72 to 0.60 units/kg/day.\n\nMediation analysis showed that at week 4, 83% of the TDD reduction (-11.1 U/day) was a direct drug effect and only 17% (-2.3 U/day) was from weight loss. By week 26, it was 52% direct effect (-11.4 U/day) and 48% weight loss (-10.5 U/day). Daily carbohydrate intake decreased from 137g to 107g.","whyItMatters":"Type 1 diabetes with obesity is a growing problem, and high insulin doses contribute to weight gain, creating a vicious cycle. Semaglutide's ability to reduce insulin needs — especially mealtime insulin — while also promoting weight loss could break this cycle. The finding that most of the early insulin reduction is a direct drug effect (not dependent on weight loss) is particularly important, as it means patients see benefits almost immediately. This could improve quality of life by simplifying insulin management and reducing hypoglycemia risk.","specificNumbers":"","methodology":"This was a post hoc analysis of the ADJUST-T1D trial, a double-blind, multicenter, randomized, placebo-controlled trial of semaglutide 1 mg/week in adults with type 1 diabetes and obesity using automated insulin delivery systems. Changes in total daily insulin dose, basal and bolus insulin, carbohydrate intake, and user-initiated bolus counts were analyzed over 26 weeks using linear mixed models. Mediation analysis separated the direct drug effect from weight-loss-mediated insulin reduction.","limitations":"This is a post hoc analysis (not pre-specified), which limits the strength of causal conclusions. The specific sample size is not stated in the abstract. The study lasted only 26 weeks, so long-term effects on insulin needs are unknown. All participants used automated insulin delivery systems, which may limit generalizability to patients on manual insulin regimens. The mediation analysis assumes that weight loss and direct drug effects are the only pathways, which may oversimplify the mechanism."},{"rthcId":"RPEP-11726","title":"Association of British Clinical Diabetologists and UK Kidney Association Joint Clinical Practice Guidelines for the Pharmacological Management of Hyperglycemia in Adults With Type 2 Diabetes Mellitus and CKD.","authors":"Karalliedde, Janaka; McCafferty, Kieran; Winocour, Peter; Chowdhury, Tahseen A; Kanumilli, Naresh; De, Parijat; Frankel, Andrew H; Doherty, Ciara; Milne, Nicola; Montero, Rosa M; Loudaki, Eirini; Banerjee, Debasish; Mallik, Ritwika; Sharif, Adnan; Zac-Varghese, Sagen; Bellary, Srikanth; Goldet, Gabrielle; Dhatariya, Ketan; Bain, Stephen C; Dasgupta, Indranil","year":2025,"journal":"Kidney international reports, 10(10), 3318-3331","doi":"10.1016/j.ekir.2025.07.028","pmid":"41141497","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11727","title":"Effects of Glucagon-Like Peptide-1 receptor agonists on bone health in people living with obesity.","authors":"Karam, Léa; Mabilleau, Guillaume; Paccou, Julien","year":2025,"journal":"Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 36(11), 2115-2126","doi":"10.1007/s00198-025-07664-1","pmid":"40920189","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In rodent models, liraglutide positively influenced bone material properties despite weight loss, but the most favorable effects on bone mineral density and microarchitecture occurred at doses much higher than those approved for human obesity treatment.\n\nIn humans with obesity, preliminary findings indicate GLP-1 receptor agonists cause modest bone mineral density reduction and enhance bone remodeling that favors resorption — a pattern similar to the effects seen with calorie restriction producing 7–10% weight loss. Significant weight reduction through calorie restriction or bariatric surgery consistently results in high-turnover bone loss.","whyItMatters":"With millions of people now using GLP-1 drugs for weight loss, understanding their bone health implications is critical — especially since significant weight loss from any cause is known to reduce bone density. This review helps clarify whether bone changes seen with these drugs are a direct drug effect or simply a consequence of losing weight.","specificNumbers":"","methodology":"This was a comprehensive literature review of preclinical studies and human data published in English from January 2013 to December 2024. The authors searched for studies examining the effects of GLP-1 receptor agonists on bone health, and also summarized data on bone outcomes from calorie restriction and bariatric surgery for context.","limitations":"Current evidence on GLP-1 RA effects on bone health in humans with obesity is limited. Most robust bone data comes from animal models using doses higher than those used clinically. The review did not include fracture outcome data, which would be the most clinically meaningful endpoint. The bone effects may be confounded by weight loss itself rather than representing a direct drug effect."},{"rthcId":"RPEP-11728","title":"Comparative Effectiveness and Safety of Oral Versus Subcutaneous Semaglutide in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.","authors":"Karedath, Jithin; Nall, Scott; Kaur, Mandeep; Lokhandwala, Adnan; Aqel, Yousef H; Maali Abusal, Abdelaziz; Wei, Calvin R; Allahwala, Danish","year":2025,"journal":"Cureus, 17(4), e82497","doi":"10.7759/cureus.82497","pmid":"40385819","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11729","title":"Increased Weight Loss With the Combination of Levoketoconazole and Semaglutide in a Patient With Mild Hypercortisolism.","authors":"Kargutkar, Smita","year":2025,"journal":"AACE endocrinology and diabetes, 12(3), 146-149","doi":"10.1016/j.aed.2025.06.009","pmid":"41048691","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11730","title":"The anti-aging potential of antihypertensive peptides of Pariset, a dataset of algal peptides.","authors":"Karimi, Isaac; Olfati, Parisa; Mohammed, Layth Jasim; Kadhim Tarrad, Jawad; Amshawee, Ahmed M; Hussain, Maryam A; Schiöth, Helgi B","year":2025,"journal":"Frontiers in aging, 6, 1618082","doi":"10.3389/fragi.2025.1618082","pmid":"40809316","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11731","title":"The Diagnostic Utility of Brain Natriuretic Peptide in Heart Failure Patients Presenting with Acute Dyspnea: A Systematic Review and Meta-analysis.","authors":"Karimi, Mohammad Amin; Kazemi Ferezghi, Zahra; Khademi, Reza; Mazhari, Seyed Amirhossein; Chichagi, Fatemeh; Rasouli, Asma; Alikhani, Reyhaneh; Sani, Anis; Akhavan Rezayat, Shima; Shakouri, Nima; Azimi, Seyed Iraj; Jadidian, Faezeh; Nikeghbali, Golnaz; Edrisian, Mahfam; Alizadeh, Alaleh; Deravi, Niloofar; Poudineh, Mohadeseh; Asadi Anar, Mahsa","year":2025,"journal":"Acta medica Indonesiana, 57(2), 175-199","doi":null,"pmid":"40641207","tags":[],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"BNP (B-type natriuretic peptide) and NT-proBNP showed comparable diagnostic accuracy for heart failure in patients presenting with acute dyspnea. Across 26 studies (n=16,002) for BNP and 14 studies (n=6,313) for NT-proBNP, pooled sensitivity and specificity overlapped with no statistically significant difference between the two biomarkers.\n\nAs with any threshold-dependent test, raising the BNP cutoff increased specificity but decreased sensitivity. The lowest reported sensitivity was 0.76 at a BNP cutoff of ≥500 pg/mL in a study with 46% heart failure prevalence. The authors note a residual risk of missed heart failure diagnoses with either biomarker.","whyItMatters":"Acute dyspnea (sudden shortness of breath) is one of the most common emergency department presentations, and quickly distinguishing heart failure from other causes is critical for treatment. BNP and NT-proBNP are the most widely used peptide biomarkers for this purpose. This meta-analysis confirms that both perform similarly, giving clinicians confidence that either test is appropriate, while also highlighting that neither is perfect — some heart failure cases will still be missed.","specificNumbers":"35 qualifying studies · BNP: 26 studies, n=16,002 · NT-proBNP: 14 studies, n=6,313 · Lowest BNP sensitivity: 0.76 at ≥500 pg/mL · No significant difference between BNP and NT-proBNP (p>0.05)","methodology":"Systematic review and meta-analysis following PRISMA guidelines. The researchers searched PubMed/Medline, Scopus, and Google Scholar through March 2023 for cross-sectional and cohort studies evaluating BNP and NT-proBNP in heart failure patients with acute dyspnea. Publication bias was assessed using Deeks' funnel plot asymmetry test. Diagnostic accuracy (sensitivity and specificity) was pooled across studies.","limitations":"Significant heterogeneity existed between studies in reported sensitivity and specificity, likely reflecting different BNP cutoff thresholds, patient populations, and heart failure prevalence. The search only extended through March 2023. The authors acknowledge that larger future studies are needed to establish consensus cutoff values. Some heart failure cases may be missed by either biomarker."},{"rthcId":"RPEP-11732","title":"Efficacy of Esaxerenone Plus a Renin-Angiotensin System Inhibitor or Calcium Channel Blocker for Nocturnal Hypertension: A Post Hoc Analysis.","authors":"Kario, Kazuomi; Ito, Sadayoshi; Itoh, Hiroshi; Rakugi, Hiromi; Okuda, Yasuyuki; Yamakawa, Satoru","year":2025,"journal":"American journal of hypertension, 38(8), 605-611","doi":"10.1093/ajh/hpaf048","pmid":"40178088","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 270 patients with uncontrolled hypertension, esaxerenone treatment produced significant nocturnal blood pressure reductions across all groups:\n\n- Monotherapy (n=172): 24h SBP -10.0 mmHg\n- With calcium channel blocker (n=49): 24h SBP -6.0 mmHg\n- With RAAS inhibitor (n=49): 24h SBP -17.0 mmHg\n\nNighttime systolic BP decreased significantly (P < 0.001) in all groups by week 28, with the RAAS inhibitor combination showing the greatest effect (-20.6 mmHg nighttime SBP). NT-proBNP (N-terminal pro-B-type natriuretic peptide), a peptide biomarker of cardiovascular prognosis, decreased significantly in all three treatment groups.","whyItMatters":"Nocturnal hypertension is particularly dangerous because it indicates the cardiovascular system isn't getting adequate rest during sleep. The combination of esaxerenone with a renin-angiotensin system inhibitor targets two key peptide-mediated pathways: aldosterone (mineralocorticoid) and angiotensin. The significant reduction in NT-proBNP — a natriuretic peptide fragment that rises with cardiac stress — suggests this combination not only lowers pressure but actually reduces the cardiovascular burden, which may translate to fewer heart failure events.","specificNumbers":"","methodology":"Post hoc analysis of a multicenter, open-label, phase 3 study in Japanese patients with uncontrolled hypertension. 270 patients were analyzed across three groups: esaxerenone monotherapy (n=172), esaxerenone + calcium channel blocker (n=49), and esaxerenone + RAS inhibitor (n=49). 24-hour ambulatory blood pressure monitoring assessed nighttime and daytime BP at baseline and week 28. NT-proBNP levels were measured as a cardiovascular biomarker endpoint.","limitations":"This is a post hoc analysis of an open-label (non-blinded) trial, which is methodologically weaker than a pre-planned blinded analysis. The study was conducted exclusively in Japanese patients, and blood pressure responses may differ in other populations. Sample sizes in the combination groups were small (49 each). The study lacked a placebo control group. The 28-week duration may not capture long-term cardiovascular outcome benefits."},{"rthcId":"RPEP-11733","title":"Plasma SuPAR and therapeutic response to erenumab in migraine: a REFORM study.","authors":"Karlsson, William K; Christensen, Rune H; Al-Khazali, Haidar M; Kallemose, Thomas; Jawad, Baker N; Andersen, Ove; Ashina, Messoud; Ashina, Håkan","year":2025,"journal":"The journal of headache and pain, 26(1), 86","doi":"10.1186/s10194-025-02037-9","pmid":"40275185","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11734","title":"Evaluating the Efficacy of ChatGPT vs. Google Gemini in Generating Patient Education Materials for GLP-1 Receptor Agonists (Semaglutide, Liraglutide, Tirzepatide): A Cross-Sectional Study.","authors":"Karnan, Nithin; Nair, Sruthi; Fidai, Farhaan Firoz; Gurrala, Sri Vidhya; Salim, Jasmine; Gomma, Ahmed","year":2025,"journal":"Cureus, 17(4), e81993","doi":"10.7759/cureus.81993","pmid":"40351930","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11735","title":"US eligibility and preventable cardiovascular disease events from semaglutide in type 2 diabetes.","authors":"Karthikeyan, Hridhay; Fan, Wenjun; Wong, Nathan D","year":2025,"journal":"Diabetes & vascular disease research, 22(5), 14791641251376551","doi":"10.1177/14791641251376551","pmid":"40908778","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11736","title":"Proteomic-based biomarker discovery reveals panels of diagnostic biomarkers for early identification of heart failure subtypes.","authors":"Karuna, Narainrit; Tonry, Claire; Ledwidge, Mark; Glezeva, Nadezhda; Gallagher, Joe; McDonald, Ken; Watson, Chris J","year":2025,"journal":"Journal of translational medicine, 23(1), 546","doi":"10.1186/s12967-025-06563-7","pmid":"40375290","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11737","title":"Comparative Efficacy and Tolerability of Tirzepatide Versus Semaglutide at Varying Doses for Weight Loss in Non-diabetic Adults With Obesity: A Network Meta-Analysis of Randomized Controlled Trials.","authors":"Kasagga, Alousious; Rebellow, Delvy; Hashmi, Tooba; Husami, Malik Y; Lama, Pooja; Arul Selvan, Kaavya; Nakasagga, Kevin","year":2025,"journal":"Cureus, 17(8), e90335","doi":"10.7759/cureus.90335","pmid":"40978842","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11738","title":"Dose-Dependent Efficacy and Safety of Tirzepatide for Weight Loss in Non-diabetic Adults With Obesity: A Systematic Review and Meta-analysis of Randomized Controlled Trials.","authors":"Kasagga, Alousious; Assefa, Amanuel Kefyalew; Amin, Maysaa N; Hashish, Rahma; Agha Tabari, Khaled; Swami, Shivling S; Nakasagga, Kevin","year":2025,"journal":"Cureus, 17(6), e85531","doi":"10.7759/cureus.85531","pmid":"40630338","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Pooled analysis of 4 RCTs (n=3,553) demonstrated:\n\n- Mean body weight reduction: -16.54% vs. placebo (95% CI: -17.48 to -15.59; p<0.00001)\n- Clear dose-response: each 1 mg increase in tirzepatide added -0.72% more weight loss (meta-regression p=0.0014)\n- Achievement of ≥15% weight loss: OR 23.25 (95% CI: 18.06-29.94)\n- BMI reduction: -7.09 kg/m²\n- Waist circumference reduction: -12.77 cm\n- HbA1c improvement: -0.42%\n- Quality of life improved (SF-36v2 and IWQOL-Lite-CT scores)\n\nSafety: Nausea (OR 4.20), vomiting (OR 6.93), and diarrhea (OR 3.80) were more common, but serious adverse events were comparable to placebo (OR 0.97).","whyItMatters":"Obesity affects over 40% of American adults and drives type 2 diabetes, heart disease, and numerous other conditions. Tirzepatide's 16.5% average weight loss approaches what was previously only achievable through bariatric surgery. This meta-analysis quantifies the dose-response relationship for the first time, helping clinicians optimize dosing, and confirms that despite GI side effects, serious adverse events are no more common than placebo — a critical finding for a medication intended for long-term use.","specificNumbers":"","methodology":"Systematic review and meta-analysis of RCTs. PubMed, Cochrane CENTRAL, and ClinicalTrials.gov were searched (January 2020 to April 2025). Inclusion criteria: tirzepatide (5-15 mg or MTD) vs. placebo, minimum 52 weeks, non-diabetic obese adults. Data pooled using fixed- or random-effects models. Dose-response meta-regression performed. Sensitivity analyses confirmed reliability.","limitations":"Only 4 RCTs met inclusion criteria, limiting the statistical power for subgroup analyses. All trials had at least 52 weeks duration, but longer-term data on weight regain after discontinuation are limited. The meta-analysis focused on non-diabetic adults, so results may not apply to people with type 2 diabetes. Gastrointestinal side effects were significantly higher, which could affect real-world adherence. The analysis did not separate effects by sex, age, or baseline BMI."},{"rthcId":"RPEP-11739","title":"Correlation Between decreased mixed venous oxygen saturation and increased B-type natriuretic peptides independent of hemodynamics in pre-heart failure/heart failure patients.","authors":"Kashiwagi, Yusuke; Nagoshi, Tomohisa; Funaki, Ryuji; Mashitani, Yuto; Ito, Satoshi; Ogawa, Kazuo; Kawai, Makoto; Tokuda, Michifumi; Yoshimura, Michihiro","year":2025,"journal":"Peptides, 192, 171433","doi":"10.1016/j.peptides.2025.171433","pmid":"40706756","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11740","title":"Role of neoadjuvant peptide receptor radionuclide therapy in unresectable and metastatic gastro-entero-pancreatic neuroendocrine neoplasms: A scoping review.","authors":"Kashyap, Raghava; Raja, Senthil; Adusumilli, Ajay; Gopireddy, Murali Mohan Reddy; Loveday, Benjamin P T; Alipour, Ramin; Kong, Grace","year":2025,"journal":"Journal of neuroendocrinology, 37(3), e13425","doi":"10.1111/jne.13425","pmid":"38937270","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11741","title":"Designing an Entactin-Inspired Short Bioactive Hydrogel as Biofunctional Scaffold.","authors":"Kashyap, Shambhavi; Mohanty, Sweta; Sen, Sourav; Roy, Sangita","year":2025,"journal":"Chembiochem : a European journal of chemical biology, 26(14), e202500260","doi":"10.1002/cbic.202500260","pmid":"40404607","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11742","title":"Glucagon-like peptide 1 receptor agonists switching patterns in type two diabetes: A retrospective real-world study.","authors":"Kassem, Sameer; Khalaila, Buthaina; Stein, Nili; Zaina, Adnan","year":2025,"journal":"World journal of diabetes, 16(11), 112999","doi":"10.4239/wjd.v16.i11.112999","pmid":"41278443","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11743","title":"Diabetes with GLP-1R polymorphism (rs3765467) accompanied by myotonic dystrophy: A case of myotonic dystrophy with p.R131Q polymorphism at the glucagon-like peptide-1 receptor (rs3765467) resulting in marked effects of its agonist, dulaglutide.","authors":"Kato, Kanako; Jojima, Teruo; Kogai, Takahiko; Tanuma, Dai; Niitani, Takafumi; Sakurai, Shintaro; Iijima, Toshie; Tomaru, Takuya; Usui, Isao; Aso, Yoshimasa","year":2025,"journal":"The American journal of the medical sciences, 369(1), 126-130","doi":"10.1016/j.amjms.2024.06.030","pmid":"38986908","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11744","title":"Impact of Tirzepatide on diet-related quality of life and treatment satisfaction in people with type 2 diabetes mellitus: a retrospective cross-sectional study.","authors":"Kato, Shunsuke; Kokita, Ayaka; Akanuma, Hana; Iwamura, Shogo; Takahashi, Yuya; Kusumi, Ryota; Abe, Sakiko; Sasaki, Kana; Otomo, Hitomi; Ando, Sayaka; Nara, Mitsuhiko; Nara, Aiko; Tadika, Takenobu; Shimizu, Tatsunori; Sato, Takehiro; Morii, Tsukasa; Fujita, Hiroki; Matsuda, Daisuke; Waki, Hironori","year":2025,"journal":"Diabetes research and clinical practice, 229, 112913","doi":"10.1016/j.diabres.2025.112913","pmid":"40983113","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tirzepatide treatment in 95 people with type 2 diabetes led to significant reductions in HbA1c (from 7.4% to 6.4%) and body weight (from 77.2 kg to 70.6 kg). Notably, despite tirzepatide's appetite-suppressing effects, patients reported significantly improved diet-related quality of life — specifically their perception of dietary therapy's benefits increased from a median score of 58.3 to 67.7 (p<0.01).\n\nMultiple regression analysis showed that both BMI reduction and improved diet-related quality of life were independent predictors of overall treatment satisfaction, with comparable effect sizes.","whyItMatters":"Weight loss drugs that suppress appetite might be expected to make eating less enjoyable, reducing quality of life around food. This study found the opposite — patients on tirzepatide actually felt better about their dietary habits. This is important because treatment satisfaction drives long-term adherence, and knowing that patients feel positively about diet changes could support better real-world outcomes.","specificNumbers":"","methodology":"This was a retrospective cross-sectional study of 95 people with type 2 diabetes treated with tirzepatide. Researchers compared clinical measurements (BMI, HbA1c) and validated questionnaire responses (diet-related quality of life via DDRQOL-R-9, treatment satisfaction via DTSQs) before and after treatment. Spearman correlations and multiple regression analyses were used to identify predictors of satisfaction.","limitations":"As a retrospective, cross-sectional study without a control group, it cannot establish causation. The sample size of 95 is modest. Patient-reported outcomes may be influenced by overall improvement in health metrics. The study does not report treatment duration or tirzepatide dose details in the abstract."},{"rthcId":"RPEP-11745","title":"Dose-dependent renoprotective effects of sacubitril/valsartan in heart failure: a retrospective study.","authors":"Kato, Takahiro; Nakano, Yusuke; Yasukawa, Noriko; Oonishi, Masafumi; Hamada, Yukihiro","year":2025,"journal":"Renal failure, 47(1), 2538830","doi":"10.1080/0886022X.2025.2538830","pmid":"40841853","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11746","title":"Psychiatric adverse events linked to glucagon-like peptide 1 analogues: a disproportionality analysis in American, Canadian and Australian adverse event databases.","authors":"Katranski, Jonah; Liang, Sihua; Morris, Deirdre; Suppiah, Vijayaprakash; Lim, Chiao Xin","year":2025,"journal":"International journal of clinical pharmacy, 47(6), 1739-1747","doi":"10.1007/s11096-025-01943-x","pmid":"40522403","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide showed the strongest psychiatric safety signals: depressive symptoms (ROR = 6.24, CI 4.49–8.69 in FAERS), suicidal ideation (ROR = 2.58, CI 2.31–2.88 in FAERS), and panic attacks (ROR = 1.46, CI 1.16–1.82 in FAERS). Liraglutide was linked to depression in the Canadian database (ROR = 1.68, CI 1.12–2.51). Dulaglutide was associated with eating disorders (ROR = 1.47, CI 1.26–1.71) and insomnia (ROR = 2.93, CI 2.35–3.66) in FAERS.\n\nSignificant associations were identified when multiple databases showed elevated reporting odds ratios, strengthening the signal reliability.","whyItMatters":"With tens of millions of people now taking GLP-1 drugs for diabetes and weight loss, understanding psychiatric risks is urgent. If semaglutide truly elevates suicide risk even modestly, the public health implications are enormous given the scale of use. These findings reinforce the need for psychiatric monitoring in patients starting these medications.","specificNumbers":"","methodology":"This pharmacovigilance study extracted psychiatric adverse event reports for all approved GLP-1 analogues from three national databases: FAERS (US), CVAROD (Canada), and DAEN (Australia). Disproportionality analysis was used to calculate reporting odds ratios (RORs) with 95% confidence intervals, comparing psychiatric event reporting rates for GLP-1 drugs against all other drugs in each database.","limitations":"Disproportionality analysis of adverse event databases can identify safety signals but cannot prove causation. Reporting biases are significant — high media attention on GLP-1 drugs may increase psychiatric event reporting (stimulated reporting). The databases lack denominator data (total prescriptions), so true incidence rates cannot be calculated. Patient-level confounders like pre-existing psychiatric conditions, obesity, and diabetes are not controlled for."},{"rthcId":"RPEP-11747","title":"Oral semaglutide for weight loss and liver fibrosis in overweight and obesity: A randomized controlled trial.","authors":"Katrevula, Anudeep; Kalapala, Rakesh; Agrawal, Siddhant; Jagtap, Nitin; Chhabra, Pratik; Kulkarni, Anand V; Merugu, Chandhana; Katukuri, Goutham Reddy; Duvvur, Nageshwar Reddy","year":2025,"journal":"Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology","doi":"10.1007/s12664-025-01856-7","pmid":"41066034","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11748","title":"Retatrutide-A Game Changer in Obesity Pharmacotherapy.","authors":"Katsi, Vasiliki; Koutsopoulos, Georgios; Fragoulis, Christos; Dimitriadis, Kyriakos; Tsioufis, Konstantinos","year":2025,"journal":"Biomolecules, 15(6)","doi":"10.3390/biom15060796","pmid":"40563436","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11749","title":"Using real-world data to predict findings of an ongoing phase IV trial: glycemic control of semaglutide versus standard of care.","authors":"Kattinakere Sreedhara, Sushama; Schneeweiss, Sebastian; D'Andrea, Elvira; Weberpals, Janick G; DiCesare, Elyse C; Patorno, Elisabetta; Tsacogianis, Theodore; Bradley, Marie; Concato, John; Wang, Shirley V","year":2025,"journal":"BMJ open diabetes research & care, 13(5)","doi":"10.1136/bmjdrc-2025-005180","pmid":"41161770","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11750","title":"Peptide pharmacology: Pioneering interventions for alcohol use disorder.","authors":"Katturajan, Ramkumar; Evan Prince, Sabina; Valsala Gopalakrishnan, Abilash","year":2025,"journal":"Progress in molecular biology and translational science, 212, 117-128","doi":"10.1016/bs.pmbts.2024.05.003","pmid":"40122643","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Preclinical research demonstrates that peptide-based therapies targeting four major neuronal systems — opioid, corticotropin-releasing factor (CRF), neuropeptide Y (NPY), and glutamate — can reduce alcohol intake, demand, and relapse in animal models of alcohol use disorder. Opioid peptides (β-endorphin, enkephalins) modulate alcohol reward via µ, δ, and κ receptors; CRF peptides reduce stress-driven alcohol seeking; and NPY peptides decrease cravings and anxiety. Early clinical trial results show translational potential, though challenges remain in establishing safety and efficacy in humans.","whyItMatters":"Alcohol use disorder affects millions of people worldwide but has very few approved pharmacological treatments. Peptide-based therapies offer a fundamentally different approach by precisely targeting the specific brain pathways that drive addiction — reward processing, stress responses, and craving — rather than using broad-acting drugs with significant side effects.","specificNumbers":"","methodology":"This is a narrative review synthesizing preclinical research on peptide-based interventions for alcohol use disorder, covering opioid peptides, CRF peptides, NPY, and glutamate system modulators. The review evaluates animal model data and early clinical trial results, and discusses translational challenges.","limitations":"As a narrative review, this article does not include systematic search methodology or meta-analysis. Most evidence discussed comes from animal models, and the translational gap between preclinical and clinical results remains significant. Specific clinical trial outcomes and effect sizes are not detailed in the abstract. Pharmacokinetic challenges of peptide delivery to the brain are acknowledged but not resolved."},{"rthcId":"RPEP-11751","title":"Efficacy, Safety, and Future of GLP-1 Receptor Agonists: A Systematic Literature Review and Meta-Analysis.","authors":"Katz, Griffin","year":2025,"journal":"Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme, 57(5), 326-337","doi":"10.1055/a-2569-7315","pmid":"40409279","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11752","title":"Could Sodium-Glucose Co-Transporter-2 Inhibitors and Glucagon-like Peptide-1 Receptor Agonists Play a Role in Gout Treatment?","authors":"Kaufmann, Dan; Schlesinger, Naomi","year":2025,"journal":"Pharmaceutics, 17(7)","doi":"10.3390/pharmaceutics17070865","pmid":"40733074","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11753","title":"Assessing the anticancer potential of spider venom peptide Latarcin Ltc2a against triple negative breast cancer.","authors":"Kaur, Prasanjeet; Roy, Srabaita; Minocha, Shilpi; Chugh, Archana","year":2025,"journal":"Biochimica et biophysica acta. Biomembranes, 1867(7), 184442","doi":"10.1016/j.bbamem.2025.184442","pmid":"40840671","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Ltc2a exhibited selective cytotoxicity toward cancer cells compared to normal cells at just 2 μM concentration. The peptide induced rapid cell death within 1 hour in breast cancer cells through membrane disruption, confirmed by propidium iodide staining and scanning electron microscopy showing visible membrane damage.\n\nIn vivo zebrafish studies demonstrated favorable peptide uptake with 80% survival at concentrations up to 4 μM, indicating low acute toxicity. Truncated variants of Ltc2a retained their alpha-helical structure and showed preferential uptake in MDA-MB-231 triple-negative breast cancer cells over normal HEK293T cells.","whyItMatters":"Triple-negative breast cancer is one of the hardest cancers to treat because it lacks the three most common targets for therapy. Finding agents that can selectively kill these cancer cells while sparing healthy tissue is a major unmet need. This study suggests that repurposing venom-derived peptides — originally evolved for microbial defense — could open a new avenue for targeted cancer treatment with potentially fewer side effects than conventional chemotherapy.","specificNumbers":"","methodology":"The researchers tested the spider venom peptide Ltc2a on triple-negative breast cancer cells (MDA-MB-231) and normal cells (HEK293T) in the lab to assess selective cytotoxicity. They used propidium iodide staining and field emission scanning electron microscopy to visualize membrane disruption. In vivo safety was evaluated in a zebrafish model, and truncated peptide variants were also tested for structural integrity and selective cell uptake.","limitations":"This study was conducted in cell cultures and zebrafish, not in mammals or humans, so it remains unclear whether the peptide would work the same way in a human body. The zebrafish model provides only a basic toxicity screen. The study did not evaluate long-term toxicity, pharmacokinetics, or tumor regression in a mammalian cancer model. Additionally, the mechanism of selectivity for cancer cells over normal cells needs further clarification."},{"rthcId":"RPEP-11754","title":"A tablespoon of mayonnaise modulates the glycemic response to rice.","authors":"Kawada, Naoki; Fujiwara, Naoki; Matsuoka, Ryosuke; Utsunomiya, Kazunori","year":2025,"journal":"Bioscience, biotechnology, and biochemistry, 90(1), 37-44","doi":"10.1093/bbb/zbaf160","pmid":"41190555","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11755","title":"Ovarian tachykinin signaling system induces the growth of secondary follicles during the gonadotropin-independent process.","authors":"Kawada, Tsuyoshi; Aoyama, Masato; Matsubara, Shin; Osugi, Tomohiro; Sakai, Tsubasa; Kirimoto, Shinji; Nakaoka, Satsuki; Sugiura, Yuki; Yasuda, Keiko; Satake, Honoo","year":2025,"journal":"The Journal of biological chemistry, 301(4), 108375","doi":"10.1016/j.jbc.2025.108375","pmid":"40043951","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11756","title":"A Melittin-Derived Peptide with Improved Cytosolic Delivery Efficiency through Caveolae- and Actin-Mediated Endocytosis.","authors":"Kawaguchi, Yoshimasa; Tamemoto, Naoki; Uehata, Yusuke; Miyazaki, Yusuke; Shinoda, Wataru; Futaki, Shiroh","year":2025,"journal":"Chemical & pharmaceutical bulletin, 73(9), 896-906","doi":"10.1248/cpb.c25-00479","pmid":"40993069","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11757","title":"Pilot Study: Functional Survival of Human Stem Cell-Derived Islets Microencapsulated With Alginate Incorporating CXCL12 in Non-Human Primates Without Systemic Immunosuppression.","authors":"Kawai, Kento; Dogan, Fatma; Alagpulinsa, David A; Pop, Ramona; Veres, Adrian; Sobell, Don; Deng, Helen; Collins, Samantha H; Zhang, Jingping; Chapin, Michael H; Markmann, James F; Lei, Ji; Poznansky, Mark C","year":2025,"journal":"Xenotransplantation, 32(6), e70098","doi":"10.1111/xen.70098","pmid":"41431325","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11758","title":"Curvature-Sensing Peptide Functions as a Membrane Interfactant That Glues Small Extracellular Vesicles to Cell Membranes and Enhances Vesicle Cellular Uptake.","authors":"Kawano, Kenichi; Hosokawa, Kenta; Taniguchi, Aoi; Oosugi, Yuuto; Soga, Akinori; Kawamoto, Jun; Kuzuma, Yuki; Matsuzaki, Katsumi","year":2025,"journal":"ACS applied bio materials, 8(12), 10839-10854","doi":"10.1021/acsabm.5c01541","pmid":"41203569","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11759","title":"Glucagon like peptide-1 receptor agonists as a promising therapeutic option of metabolic dysfunction associated steatotic liver disease and obesity: hitting two targets with one shot.","authors":"Kaya, Eda; Syn, Wing-Kin; Manka, Paul","year":2025,"journal":"Current opinion in gastroenterology, 41(3), 104-109","doi":"10.1097/MOG.0000000000001083","pmid":"39998880","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11760","title":"Oral atogepant mitigates spreading depolarization-induced pain and anxiety behavior in mice.","authors":"Kaya, Melih Z; Banerjee, Pradeep; Ayata, Cenk; Harriott, Andrea M","year":2025,"journal":"The journal of headache and pain, 26(1), 187","doi":"10.1186/s10194-025-02125-w","pmid":"40841621","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11761","title":"Multicycle Dosimetric Behavior and Dose-Effect Relationships in [177Lu]Lu-DOTATATE Peptide Receptor Radionuclide Therapy.","authors":"Kayal, Gunjan; Roseland, Molly E; Wang, Chang; Fitzpatrick, Kellen; Mirando, David; Suresh, Krithika; Wong, Ka Kit; Dewaraja, Yuni K","year":2025,"journal":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 66(6), 900-908","doi":"10.2967/jnumed.124.269389","pmid":"40274371","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Median cumulative tumor dose was 2.2 Gy/GBq (range 0.1–20.8) while median kidney dose was 0.44 Gy/GBq (range 0.25–0.96). The tumor-to-kidney dose ratio declined with each cycle: 6.4, 5.7, 4.7, and 3.9 for cycles 1 through 4, driven by decreasing tumor uptake while kidney dose stayed constant.\n\nHigher-grade (grade 2) and pancreatic NETs showed a larger drop in dose per cycle and had lower overall absorbed doses and shorter effective half-lives compared to low-grade (grade 1) and small intestinal NETs.\n\nKidney radiation dose significantly predicted kidney function decline at 9 months. In a multivariable model adjusting for baseline kidney function, cycle 1 dose alone predicted 57% of the variance in later kidney function (p=0.020), and cumulative dose predicted 65% (p=0.049).","whyItMatters":"Currently, Lu-177 DOTATATE is given as a fixed dose for four cycles — one size fits all. This study provides the detailed dosimetric data needed to move toward personalized treatment, where doctors could adjust doses based on how much radiation each patient's tumors and kidneys are actually receiving. The kidney dose-prediction model is particularly valuable because kidney damage is the main dose-limiting toxicity of this peptide radionuclide therapy.","specificNumbers":"","methodology":"30 patients receiving standard Lu-177 DOTATATE therapy underwent serial SPECT/CT imaging at each treatment cycle. Kidneys were segmented automatically using a deep learning algorithm, and tumors were segmented using a SPECT-based tool guided by radiologist contours. Dosimetry was performed using Monte Carlo dose-rate mapping. Treatment response was assessed using RECIST criteria and Ga-68 DOTATATE PET imaging. Kidney toxicity was evaluated by measuring eGFR at 9 months post-treatment. 22 of 30 patients completed imaging after every cycle.","limitations":"This was a single-center study with 30 patients, and only 22 completed imaging at all four cycles. Tumor absorbed dose was not significantly associated with treatment response measures, which may reflect the complexity of response assessment or the study's limited power. No nephrotoxicity above grade 2 was observed, so the kidney dose models were not tested against severe kidney damage. The study focused on standard fixed-dose PRRT rather than dosimetry-guided dosing."},{"rthcId":"RPEP-11762","title":"Ex Vivo Modulation of the BNST by Parabrachial CGRP Projections Is Decreased After a History of Stress-Induced Anxiety.","authors":"Kayat, L S; Petersen, N; Van Doorn, C E; Nabit, B P; Tyree, J B; Centanni, S W; Jaramillo, A A","year":2025,"journal":"The European journal of neuroscience, 62(9), e70268","doi":"10.1111/ejn.70268","pmid":"41207872","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11763","title":"Staphylococcus epidermidis DnaK alters biofilm formation and proteome in Staphylococcus aureus CIP 107093.","authors":"Kayser, Clara; Druart, Karen; Bouscasse, Eleonore; Matondo, Mariette; Chane, Andréa; Hoh, François; Groboillot, Anne; Barbey, Corinne; Merieau, Annabelle; Latour, Xavier; Soule, Pierre; Mühle, Estelle; Norris, Vic; Konto-Ghiorghi, Yoan","year":2025,"journal":"Frontiers in microbiology, 16, 1705130","doi":"10.3389/fmicb.2025.1705130","pmid":"41788398","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11764","title":"Diabetes, Subclinical Myocardial Injury or Stress, and Risk of Heart Failure Subtypes: The Jackson Heart Study.","authors":"Kaze, Arnaud D; Bertoni, Alain G; Fox, Ervin R; Hall, Michael E; Mentz, Robert J; Berry, Jarett D; Echouffo-Tcheugui, Justin B","year":2025,"journal":"Diabetes care, 48(3), 464-472","doi":"10.2337/dc24-0654","pmid":"39761430","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11765","title":"Metabolic dysfunction and incidence of heart failure subtypes among Black individuals: The Jackson Heart Study.","authors":"Kaze, Arnaud D; Bertoni, Alain G; Fox, Ervin R; Hall, Michael E; Mentz, Robert J; Echouffo-Tcheugui, Justin B","year":2025,"journal":"European journal of heart failure, 27(3), 498-507","doi":"10.1002/ejhf.3447","pmid":"39225160","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11766","title":"Guts, Glucose, and Gallbladders: The Protective Role of GLP-1/GIP Receptor Agonists Against Biliary Complications in Patients with Type 2 Diabetes and Inflammatory Bowel Disease.","authors":"Kazi, Muhammad Ali Ibrahim; Singh, Sanmeet; Haq, Nowreen","year":2025,"journal":"Journal of clinical medicine, 14(24)","doi":"10.3390/jcm14248882","pmid":"41464784","tags":["glp-1-agonists","tirzepatide"],"studyType":"Retrospective Cohort Study","evidenceStrength":"moderate","keyFinding":"In a surprising finding, GLP-1 and dual GLP-1/GIP drugs (semaglutide and tirzepatide) were associated with substantially reduced — not increased — risks of gallstone-related complications in patients who have both type 2 diabetes and inflammatory bowel disease. After propensity score matching 32,052 patients (16,026 per group), the GLP-1 group had significantly fewer cases of gallstones (cholelithiasis), gallbladder inflammation (cholecystitis), bile duct stones (choledocholithiasis), and bile duct infection (cholangitis).\n\nThis contradicts the general concern that GLP-1 drugs increase gallbladder problems, though this specific population (T2DM + IBD) has a uniquely high baseline risk for biliary complications.","whyItMatters":"Gallbladder problems are one of the most-discussed side effects of GLP-1 drugs. Clinical trials like SELECT have shown slightly increased gallstone rates. But this study suggests that in patients with IBD — who already face elevated biliary risk — GLP-1 drugs may actually be protective. This could change clinical decision-making for a population that often avoids GLP-1 drugs due to gallbladder concerns.","specificNumbers":"n=32,052 matched patients · 16,026 per cohort · reduced cholelithiasis, cholecystitis, choledocholithiasis (all p significant) · cholangitis trended lower (p=0.08) · TrinetX global database","methodology":"Retrospective cohort study using the TrinetX LIVE global health research network. Adults with coexisting T2DM and IBD were divided into those prescribed semaglutide or tirzepatide versus those with no GLP-1/GIP therapy. Propensity score matching (1:1, caliper 0.1 SD) balanced demographics, comorbidities, GI surgical history, and other diabetes medications. Primary outcomes were identified by ICD-10 codes for gallstone-related conditions.","limitations":"Retrospective observational design cannot prove causation. ICD-10 codes may miss or misclassify diagnoses. The TrinetX database may have coding biases. The study doesn't distinguish between semaglutide and tirzepatide effects. Patients who tolerate GLP-1 drugs may be inherently healthier than those who don't start them (healthy user bias). The follow-up duration is not specified in the abstract."},{"rthcId":"RPEP-11767","title":"Uric Acid-Lowering Therapy with Febuxostat in Patients with Chronic Heart Failure and Hyperuricemia: A Prospective and Observational Cohort Study.","authors":"Ke, Jiahan; Qiu, Xiaohan; Wang, Min; Zeng, Huasu; Wang, Changqian; Zhang, Junfeng; Zhu, Huafang; Gu, Jun","year":2025,"journal":"Balkan medical journal, 42(6), 495-505","doi":"10.4274/balkanmedj.galenos.2025.2025-6-168","pmid":"40977871","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11768","title":"Oral delivery of GLP-1 peptide using recombinant Lactobacillus gasseri for the treatment of type 2 diabetes mellitus.","authors":"Ke, Zhiqiang; Ma, Qianqian; Ye, Xiaonan; Jin, Yan; Wang, Yanlin; Zhao, Xinyuan; Su, Zhengding","year":2025,"journal":"Microbiology spectrum, 13(8), e0282824","doi":"10.1128/spectrum.02828-24","pmid":"40530879","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11769","title":"Proinflammatory cytokines and neuropeptides in psoriasis, depression, and anxiety.","authors":"Keenan, Emily L; Granstein, Richard D","year":2025,"journal":"Acta physiologica (Oxford, England), 241(3), e70019","doi":"10.1111/apha.70019","pmid":"39960105","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies three neuropeptides — CGRP, substance P, and VIP — as potential biological links between psoriasis and psychiatric comorbidities. These neuropeptides are active in skin (where they drive inflammation and psoriatic lesion formation) and in the brain (where they influence mood, stress responses, and anxiety circuits).\n\nInflammatory cytokines elevated in psoriasis (IFN-γ, IL-1, IL-2, IL-6, IL-12, TNF-α, IL-22, IL-17) also cross the blood-brain barrier and affect neurotransmitter systems involved in depression. The HPA stress axis provides a bidirectional pathway where psychological stress can worsen psoriasis and psoriatic inflammation can exacerbate depression and anxiety.","whyItMatters":"Understanding the biological link between skin inflammation and mental health could transform how psoriasis is treated. If neuropeptides like CGRP and substance P drive both skin disease and mood disorders, targeting these peptides might treat both conditions simultaneously. Current psoriasis treatments that reduce inflammation may already be improving mental health — a benefit that deserves recognition and study.","specificNumbers":"","methodology":"Narrative literature review analyzing studies on the connections between psoriasis, psychiatric conditions (depression, anxiety), and biological mediators including inflammatory cytokines, neuropeptides (CGRP, substance P, VIP), and the HPA axis.","limitations":"This is a narrative review without systematic methodology. The neuropeptide-psychiatry connection in psoriasis is largely theoretical, based on the known activities of these molecules rather than direct studies proving they cause psychiatric symptoms in psoriasis patients. The relative contribution of neuropeptides versus other factors (social stigma, chronic disease burden) to psychiatric comorbidity is unclear."},{"rthcId":"RPEP-11770","title":"S100A1ct: A Synthetic Peptide Derived From S100A1 Protein Improves Cardiac Performance and Survival in Preclinical Heart Failure Models.","authors":"Kehr, Dorothea; Ritterhoff, Julia; Glaser, Manuel; Jarosch, Lukas; Salazar, Rafael E; Spaich, Kristin; Varadi, Karl; Birkenstock, Jennifer; Egger, Michael; Gao, Erhe; Koch, Walter J; Sauter, Max; Freichel, Marc; Katus, Hugo A; Frey, Norbert; Jungmann, Andreas; Busch, Cornelius; Mather, Paul J; Ruhparwar, Arjang; Busch, Martin; Völkers, Mirko; Wade, Rebecca C; Most, Patrick","year":2025,"journal":"Circulation, 151(8), 548-565","doi":"10.1161/CIRCULATIONAHA.123.066961","pmid":"39569500","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11771","title":"Antibiotic-induced gut microbiota depletion enhances glucose tolerance linked to GLP-1 signaling.","authors":"Kellenberger, Alexandra; Dewal, Revati Sumukh; de Wouters d'Oplinter, Alice; Sichert, Andreas; Heine, Markus; Fuh, Marceline M; Slack, Emma; Delessa Challa, Tenagne; Wolfrum, Christian","year":2025,"journal":"Frontiers in endocrinology, 16, 1684155","doi":"10.3389/fendo.2025.1684155","pmid":"41393294","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11772","title":"LL37 complexed to double-stranded RNA induces RIG-I-like receptor signalling and Gasdermin E activation facilitating IL-36γ release from keratinocytes.","authors":"Keller, Jennifer; Danis, Judit; Krehl, Isabella; Girousi, Eleftheria; Satoh, Takashi K; Meier-Schiesser, Barbara; Kemény, Lajos; Széll, Márta; Wong, W Wei-Lynn; Pascolo, Steve; French, Lars E; Kündig, Thomas M; Mellett, Mark","year":2025,"journal":"Cell death & disease, 16(1), 198","doi":"10.1038/s41419-025-07537-9","pmid":"40121229","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11773","title":"Effect of Glucagon-Like Peptide 1 Receptor Agonists on Patients With Rheumatoid Arthritis.","authors":"Kellner, David A; Dente, Elizabeth; Tran, Vincent; Welsh, Travis; Tran, Victor; Saha, Angshuman; Baker, Joshua F; Elashoff, David A; Ranganath, Veena K","year":2025,"journal":"ACR open rheumatology, 7(9), e70103","doi":"10.1002/acr2.70103","pmid":"40932015","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11774","title":"Approach to the Patient With Thyroid Nodules: Considering GLP-1 Receptor Agonists.","authors":"Kelly, Clare A; Sipos, Jennifer A","year":2025,"journal":"The Journal of clinical endocrinology and metabolism, 110(6), e2080-e2087","doi":"10.1210/clinem/dgae722","pmid":"39400117","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The FDA black-box warning for GLP-1 RAs applies to patients with personal/family history of medullary thyroid carcinoma (MTC) or MEN2 syndrome, based on rodent C-cell tumor data. For differentiated thyroid cancer (DTC), the evidence is conflicting: some epidemiological studies suggest increased DTC incidence in GLP-1 RA-treated patients, while others find no association. No clinical consensus exists on whether to screen patients for thyroid cancer before starting GLP-1 drugs or how to evaluate thyroid nodules found during treatment.","whyItMatters":"With tens of millions of people now taking GLP-1 drugs for diabetes and obesity, the thyroid cancer question affects an enormous population. The lack of consensus on screening and monitoring creates anxiety for both patients and prescribers. This review from the Journal of Clinical Endocrinology & Metabolism helps clinicians navigate this uncertainty with practical, case-based guidance.","specificNumbers":"","methodology":"Clinical review article using patient case presentations to contextualize existing evidence from preclinical rodent studies, epidemiological analyses, pharmacovigilance data, and clinical trials regarding thyroid cancer risk with GLP-1 RA use.","limitations":"This is a narrative clinical review, not a systematic review or meta-analysis. The conflicting evidence it describes reflects genuine uncertainty in the field — the review can't resolve the contradiction. Most thyroid cancer data comes from observational studies prone to detection bias (patients on GLP-1 drugs may receive more thyroid imaging, finding more incidental cancers). Long-term prospective data is still accumulating."},{"rthcId":"RPEP-11775","title":"Assessing customized multivalent chemokine-binding peptide treatment in a murine model of coxsackievirus B3 myocarditis.","authors":"Kelm, Nicolas; Kespohl, Meike; Smagurauskaite, Gintare; Vales, Serena; Karuppanan, Kalimuthu; Mburu, Philomena; Thiele, Arne; Pinkert, Sandra; Bukur, Thomas; Mülleder, Michael; Berndt, Nikolaus; Klingel, Karin; Gaida, Matthias M; Bhattacharya, Shoumo; Beling, Antje","year":2025,"journal":"Basic research in cardiology, 120(2), 393-422","doi":"10.1007/s00395-025-01098-w","pmid":"40009121","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11776","title":"What should the doctor prescribe-formula diet or antidiabetics? Effectiveness of formula diet-based lifestyle intervention vs. pharmacological antiglycemic therapy on weight loss and HbA1c reduction in type 2 diabetes patients-a systematic review.","authors":"Kempf, Kerstin; Röhling, Martin; Martin, Stephan","year":2025,"journal":"Frontiers in endocrinology, 16, 1644442","doi":"10.3389/fendo.2025.1644442","pmid":"41113714","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Formula diet-based lifestyle interventions produced greater weight reductions than pharmacological therapies including GIP/GLP-1 RAs and SGLT-2 inhibitors at both short-term (mean: -5.6 vs -2.6 kg under 12 months) and long-term intervals (-7.3 vs -3.1 kg at 12+ months).\n\nFor HbA1c reduction, pharmacological therapies showed a slight short-term advantage (-0.9% vs -0.6%), but long-term glycemic control was comparable between lifestyle and drug interventions (both approximately -0.7%). These results were based on 54 articles describing 3 formula diet-based programs and 47 randomized placebo-controlled pharmacological studies with a total of 87,871 patients.","whyItMatters":"GLP-1 receptor agonists and related peptide drugs are increasingly seen as the default treatment for obesity and type 2 diabetes, but they are expensive and require ongoing injections. This review provides evidence that structured formula diet programs — which are lower-cost and non-pharmacological — may actually produce better weight loss with equivalent long-term blood sugar control. This challenges the narrative that peptide drugs are the only effective option and highlights the importance of lifestyle medicine as a first-line approach.","specificNumbers":"","methodology":"Systematic review with PubMed searches through February 5, 2025. Fifty-four articles were included from 1,409 identified: 3 formula diet-based lifestyle interventions and 47 randomized, placebo-controlled pharmacological studies (GLP-1 RAs, GIP/GLP-1 combinations, SGLT-2 inhibitors). Primary and secondary outcomes were weight change (kg) and HbA1c change (%) using estimated treatment differences from intention-to-treat analyses. The total population was 87,871 patients (mean BMI 32.8 kg/m², age 60 years, 43% women).","limitations":"The comparison is indirect — formula diet studies and drug trials had different designs, populations, and comparators (no head-to-head randomized trials). Only 3 formula diet programs were included versus 47 drug studies, creating an asymmetric comparison. Formula diet adherence in real-world settings may differ from supervised study conditions. Weight regain after formula diet discontinuation was not specifically addressed. The drug comparison combines GLP-1 RAs, GIP/GLP-1 combinations, and SGLT-2 inhibitors with different mechanisms, which may mask variability between drug classes."},{"rthcId":"RPEP-11777","title":"Semaglutide-associated drug-induced liver injury: a case report and review of the literature.","authors":"Kempster, Ian; Fernandes, Darren; Saeed, Mohammed S; Sharratt, Caroline; Benfield, Sara","year":2025,"journal":"Oxford medical case reports, 2025(9), omaf177","doi":"10.1093/omcr/omaf177","pmid":"41025030","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A middle-aged female patient presented with rapidly worsening liver function tests one month after starting semaglutide. The clinical workup was thorough:\n\n- Non-invasive liver screen: negative\n- Viral hepatitis studies: negative\n- Ultrasound and CT imaging: no structural cause identified\n- Liver biopsy: findings consistent with drug-induced liver injury\n\nThe patient experienced transient liver failure but improved with supportive treatment and withdrawal of semaglutide. No other cause for the liver injury was identified, supporting semaglutide as the causative agent.","whyItMatters":"Semaglutide is now one of the most widely used medications globally, prescribed for type 2 diabetes and obesity. Its use has expanded dramatically since 2021, including through unregulated channels for weight loss. While liver injury appears to be rare, the sheer number of users means even rare adverse events will affect many people. Clinicians and patients need to be aware that liver injury is a possible complication, especially since early recognition and drug withdrawal can prevent progression to severe liver failure.","specificNumbers":"","methodology":"This is a single case report with a brief review of the literature. The patient underwent comprehensive diagnostic evaluation including liver function tests, non-invasive liver screening, viral studies, ultrasound, CT imaging, and liver biopsy to exclude alternative diagnoses and confirm drug-induced liver injury.","limitations":"This is a single case report — the lowest level of clinical evidence. While the temporal relationship (onset one month after starting semaglutide) and the thorough exclusion of other causes support a causal link, a single case cannot establish the frequency of this adverse event or prove definitive causation. The specific mechanism of liver injury is unknown. Individual patient factors may have contributed."},{"rthcId":"RPEP-11778","title":"A Case Report of Bezoar-Induced Small Bowel Obstruction: A Potential Surgical Complication of Semaglutide.","authors":"Keng, Cambo; Thor, Sze Mun; Balasubramaniam, Ramana; Pretorius, Frans","year":2025,"journal":"Cureus, 17(12), e99664","doi":"10.7759/cureus.99664","pmid":"41431486","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11779","title":"Neuroprotective Role of the Novel GLP-1R Agonist Semaglutide.","authors":"Kenzheshova, Akniyet; Moldasheva, Aiman; Aljofan, Mohamad","year":2025,"journal":"Current medicinal chemistry","doi":"10.2174/0109298673359635250401051339","pmid":"40277068","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies the molecular connections between type 2 diabetes and Alzheimer's disease:\n\n- Impaired brain insulin signaling leads to neuronal degeneration and reduced synaptic activity\n- GLP-1 naturally plays a role in brain glucose control and insulin signaling\n- GLP-1 receptor agonists demonstrate neuroprotective properties including: prevention of neuronal death, inhibition of amyloid-beta (Aβ) accumulation, and mitigation of tau hyperphosphorylation\n- Semaglutide, despite being the most widely used GLP-1RA, has had limited focused neuroprotection studies compared to older GLP-1 drugs like liraglutide and exenatide\n\nThe review calls for more semaglutide-specific research given its unique pharmacological properties (longer half-life, higher potency) compared to earlier GLP-1 drugs.","whyItMatters":"With semaglutide prescribed to tens of millions of people, understanding its brain effects is critical. Alzheimer's disease affects over 55 million people worldwide, and there is growing evidence that GLP-1 drugs provide neuroprotection beyond their metabolic benefits. Semaglutide is currently in clinical trials for Alzheimer's (the EVOKE and EVOKE+ trials), and this review provides the mechanistic framework for understanding why these trials were initiated and what outcomes to expect.","specificNumbers":"","methodology":"This is a narrative review examining the literature on molecular mechanisms linking Alzheimer's disease and type 2 diabetes, the neuroprotective properties of GLP-1 receptor agonists, and specifically the limited evidence on semaglutide's brain effects.","limitations":"This is a narrative review, not a systematic review, so the literature coverage may not be comprehensive. The neuroprotective evidence for semaglutide is largely extrapolated from studies of other GLP-1 drugs (liraglutide, exenatide), and semaglutide-specific brain data is limited. The review does not discuss the EVOKE/EVOKE+ clinical trial results (which may not have been available). Animal model findings may not translate to human Alzheimer's disease. The blood-brain barrier penetration of semaglutide and its direct versus indirect brain effects remain debated."},{"rthcId":"RPEP-11780","title":"Home-Based Care Management for Patients Post-Heart Failure Index Hospitalization: A Comprehensive Review.","authors":"Kerkar, Prafulla; Harikrishnan, Sivadasanpillai; Sawhney, Jp S; Kapoor, Aditya; Gharat, Chetan","year":2025,"journal":"Cureus, 17(4), e83017","doi":"10.7759/cureus.83017","pmid":"40421332","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11781","title":"GLP-1 Receptor Agonists - Good for Body Weight, Bad for Micronutrient Status?","authors":"Kerlikowsky, Felix; Krämer, Klaus; Eggersdorfer, Manfred; Hahn, Andreas","year":2025,"journal":"Current developments in nutrition, 9(11), 107587","doi":"10.1016/j.cdnut.2025.107587","pmid":"41328178","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11782","title":"AI-assisted assessment of the IFSO consensus on obesity management medications in the context of metabolic bariatric surgery.","authors":"Kermansaravi, Mohammad; Salminen, Paulina; Prager, Gerhard; Cohen, Ricardo V","year":2025,"journal":"PLOS digital health, 4(12), e0001132","doi":"10.1371/journal.pdig.0001132","pmid":"41417777","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11783","title":"An Overview of Currently Available Injectable Therapies in Diabetes: A Guide to Practitioners.","authors":"Kesavadev, Jothydev; Basanth, Anjana; Shankar, Arun; Saboo, Banshi; Mohan, Anjana Ranjit; Joshi, Shashank; Ghosh, Sujoy; Krishnan, Gopika; Jothydev, Krishnadev; Ashik, Asha","year":2025,"journal":"Advances in therapy, 42(8), 3634-3656","doi":"10.1007/s12325-025-03250-3","pmid":"40481909","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11784","title":"LL-37, the master antimicrobial peptide, its multifaceted role from combating infections to cancer immunity.","authors":"Keshri, Anand K; Rawat, Suraj S; Chaudhary, Anubha; Sharma, Swati; Kapoor, Ananya; Mehra, Parul; Kaur, Rimanpreet; Mishra, Amit; Prasad, Amit","year":2025,"journal":"International journal of antimicrobial agents, 65(1), 107398","doi":"10.1016/j.ijantimicag.2024.107398","pmid":"39643165","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"LL-37, the only human cathelicidin antimicrobial peptide, has demonstrated activity across three domains of infection — bacterial, fungal, and viral — through distinct mechanisms. Against bacteria, it disrupts cell membranes. Against fungi, it inhibits growth. Against viruses, it interferes with replication. Additionally, LL-37 shows immunomodulatory effects and direct cytotoxicity against cancer cells, positioning it as a potential multi-purpose therapeutic molecule.","whyItMatters":"As antibiotic resistance grows, there's urgent need for alternatives. LL-37 is produced naturally by the human body, making it a well-tolerated starting point for drug development. Its ability to fight infections across multiple pathogen types while also modulating immune responses against cancer makes it unusually versatile compared to conventional antibiotics that target only bacteria.","specificNumbers":"","methodology":"This is a narrative review article that synthesizes published research on LL-37's antimicrobial and anti-cancer properties. The authors surveyed the literature on LL-37's mechanisms of action against bacteria, fungi, viruses, and cancer cells.","limitations":"As a review article, this paper does not present original experimental data. Most LL-37 research has been preclinical (lab and animal studies), with limited human clinical trial data. The therapeutic potential described is largely theoretical and would require extensive clinical testing."},{"rthcId":"RPEP-11785","title":"Glucagon-like Peptide-1 Receptor Agonists and Reproductive Health: Current Evidence and Clinical Implications.","authors":"Kettner, Jordyn; Donnelly, Elizabeth; Maes, Marina L","year":2025,"journal":"Journal of pharmacy practice, 8971900251376795","doi":"10.1177/08971900251376795","pmid":"40906565","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11786","title":"Post-burn Lung Inflammation Is Associated With Induction of Pulmonary Cathelicidin-related Antimicrobial Peptide and S100a8 in Mice.","authors":"Khair, Shanawaj; Najarro, Kevin M; Walrath, Travis M; Orlicky, David J; McMahan, Rachel H; Kovacs, Elizabeth J","year":2025,"journal":"Journal of burn care & research : official publication of the American Burn Association, 46(4), 917-926","doi":"10.1093/jbcr/iraf069","pmid":"40341915","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11787","title":"GLP-1 Receptor Agonist Use in Patients Undergoing Distal Radius Fracture Surgery: A Retrospective Review of Perioperative Considerations.","authors":"Khak, Mohammad; Adams, Jeremiah A; Hozien, Muhammad; Ilyas, Asif M","year":2025,"journal":"Cureus, 17(7), e89183","doi":"10.7759/cureus.89183","pmid":"40895987","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11788","title":"An insight into cell-penetrating peptides: perspectives on design, optimization, and targeting in drug delivery systems.","authors":"Khakshur, Ali Asghar; Khodaverdi, Elham; Kamali, Hossein; Nokhodchi, Ali","year":2025,"journal":"Pharmaceutical development and technology, 30(5), 521-547","doi":"10.1080/10837450.2025.2505000","pmid":"40356455","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11789","title":"Semaglutide exposure and its association with adverse outcomes in diabetic patients undergoing transforaminal lumbar interbody fusion for lumbar degenerative disc disease.","authors":"Khalid, Syed I; Massaad, Elie; Thomson, Kyle; Shin, John H","year":2025,"journal":"Journal of neurosurgery. Spine, 42(1), 1-8","doi":"10.3171/2024.6.SPINE24141","pmid":"39366019","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"After 1:3 propensity score matching on 10 variables (age, sex, obesity, hypertension, coronary artery disease, chronic kidney disease, smoking, osteoporosis, levels of surgery, and insulin dependence), the semaglutide-exposed group showed a dramatically higher odds of needing additional lumbar fusion surgery within one year: OR 11.79 (95% CI 8.17–17.33).\n\nKaplan-Meier survival analysis with log-rank testing confirmed a statistically significant divergence in the probability of additional surgery between cohorts (P < 0.001). The association was stronger in patients receiving semaglutide for longer durations, suggesting a dose-duration relationship.","whyItMatters":"Millions of people now take semaglutide for diabetes and obesity, and many of them will eventually need orthopedic surgery including spinal fusion. An odds ratio of nearly 12 for revision surgery is an extraordinary finding that could change surgical planning for these patients. If semaglutide impairs bone healing, surgeons may need to consider drug holidays before elective spinal surgery, and patients should be informed of this potential risk.","specificNumbers":"","methodology":"This retrospective matched cohort study used the MARINER all-payer database to identify patients aged 18–74 with type 2 diabetes who underwent short-segment (≤3-level) transforaminal lumbar interbody fusion (TLIF) between January 2018 and October 2022. Patients were classified as semaglutide-exposed or non-exposed. A comprehensive 1:3 matching was performed on 10 clinical variables. Primary outcome was additional lumbar fusion surgery within one year, analyzed using odds ratios, Kaplan-Meier survival curves, and log-rank testing.","limitations":"This is a retrospective database study that can show association but not causation. Despite careful matching on 10 variables, unmeasured confounders could influence the results — for example, semaglutide users may have more severe or longer-duration diabetes, greater metabolic derangement, or other factors not captured in the database. The odds ratio of 11.79 is extremely large for an observational study, which could suggest residual confounding. The database may have coding limitations that affect patient classification. Specific bone density data, nutritional status, and vitamin D levels were not available."},{"rthcId":"RPEP-11790","title":"The impact of semaglutide use for weight loss on transforaminal lumbar interbody fusion outcomes.","authors":"Khalid, Syed I; Mirpuri, Pranav; Massaad, Elie; Wang, Ryan; Elsamadicy, Aladine; Shin, John H; Adogwa, Owoicho","year":2025,"journal":"Clinical neurology and neurosurgery, 254, 108952","doi":"10.1016/j.clineuro.2025.108952","pmid":"40381509","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11791","title":"Unveiling the potential therapeutic role of nifuroxazide and liraglutide combination in mitigating LPS-induced acute lung injury through modulation of AT1R/JAK-2/STAT-3 by ACE2/ Ang1-7/MasR signaling in male albino rats: in vivo and in silico study.","authors":"Khalifa, Amira Karam; Osman, Walla''a A; Eesa, Ahmed Naeem; Ramadan, Nagwa Mahmoud; Abdelkader, Abeer; Abdallah, Sara Sayed Kadry; Aboulhoda, Basma Emad; Al-Shahed, Fatma Al-Zahraa Nabil; Alghamdi, Mansour A; Elrashedy, Ahmed A; Elshaer, Mohamed Mahmoud Abdelrahim; Saber, Sameh; Mahmoud, Alaa Karam; Ashraf, Taha; Matter, Lamiaa Mohammed","year":2025,"journal":"International immunopharmacology, 163, 115261","doi":"10.1016/j.intimp.2025.115261","pmid":"40706208","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11792","title":"Positron emission tomography to assess drug occupancy at peripheral and central incretin receptors.","authors":"Khalil, Amina; Velikyan, Irina; Xiong, Mengfei; Bossart, Martin; Wagner, Michael; Eriksson, Olof","year":2025,"journal":"EBioMedicine, 122, 106033","doi":"10.1016/j.ebiom.2025.106033","pmid":"41274021","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11793","title":"Comparative Effectiveness of Glucagon-like Peptide-1- Receptor Agonists in Patients With Heart Failure With Preserved or Minimally Reduced Ejection Fraction: A Comprehensive Bayesian Network Meta-Analysis and Network Meta-Regression.","authors":"Khalil, Ibrahim; Islam, M Rafiqul; Kamrul-Hasan, A B M; Nagendra, Lakshmi; Promi, Sunjida Amin; Sayed, Md Abu; Rahman, Mohd Turzo; Sultana, Nowrin; Tasmi, Noshin Anjum; Das, Manisha; Tarannum, Salsabil; Dey, Rajendronath; Dutta, Deep","year":2025,"journal":"Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists, 31(9), 1133-1142","doi":"10.1016/j.eprac.2025.06.005","pmid":"40553959","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11794","title":"Mirtazapine for gastrointestinal side effects of glucagon-like peptide-1 receptor agonist therapy in older adults.","authors":"Khan, Ali R; Makhoul, Gennifer Wahbah; Raji, Mukaila A","year":2025,"journal":"Endocrine regulations, 59(1), 260-264","doi":"10.2478/enr-2025-0030","pmid":"41388533","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A 72-year-old woman with cognitive impairment, type 2 diabetes, atrial fibrillation, obesity, and mood disorders was unable to escalate her semaglutide dose due to severe nausea, vomiting, and diarrhea. After initiating mirtazapine:\n\n- Gastrointestinal tolerance improved significantly\n- Semaglutide therapy was continued with successful dose advancement\n- Additional benefits included enhanced mood, better sleep, and improved overall well-being\n- No adverse effects related to mirtazapine were observed\n\nThe case suggests mirtazapine may serve as an adjunct therapy to improve GLP-1 RA tolerability and adherence.","whyItMatters":"GI side effects are the most common reason patients discontinue or fail to dose-escalate GLP-1 drugs. Finding effective strategies to manage these side effects could help millions of patients stay on their medication and reach therapeutic doses. Mirtazapine is inexpensive, widely available, and has known anti-emetic properties through 5-HT3 receptor blockade, making it a practical option.","specificNumbers":"","methodology":"This is a single-patient case report documenting the clinical course of a 72-year-old woman treated with semaglutide who developed limiting gastrointestinal side effects. Mirtazapine was added to manage these symptoms, and the clinical response was observed and reported.","limitations":"This is a single case report and cannot establish causation, efficacy, or safety in a broader population. The patient had multiple comorbidities and was taking other medications, making it difficult to isolate mirtazapine's contribution. Mirtazapine can cause weight gain, which could counteract GLP-1 drug benefits in some patients. Randomized controlled trials are needed to validate this approach."},{"rthcId":"RPEP-11795","title":"GLP-1R/NPY2R regulate gene expression, ovarian and adrenal morphology in HFD mice.","authors":"Khan, Dawood; Sridhar, Ananyaa; Moffett, Charlotte R","year":2025,"journal":"The Journal of endocrinology, 264(2)","doi":"10.1530/JOE-24-0189","pmid":"39692365","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11796","title":"Otolaryngologic Side Effects of GLP-1 Receptor Agonists.","authors":"Khan, Faizaan I; Vazquez, Sebastian Guadarrama-Sistos; Mehdi, Zain; Somawardana, Isuru; Dongre, Roshan; Razmi, Samuel; Rashidi, Keyvon; Shenoi, Jason; Khan, Najm; Dhanda, Aatin; Takashima, Masayoshi; Ahmed, Omar G","year":2025,"journal":"The Laryngoscope, 135(7), 2291-2298","doi":"10.1002/lary.32061","pmid":"39936458","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11797","title":"Permanent visual impairment following a Behçet's disease flare while on calcitonin gene-related peptide receptor antagonist therapy: a case report.","authors":"Khan, Fawad A; Malik, Alaa; Nelson, Evan; Fahimdanesh, Kian; Kaur, Karmveer; Elison, Jasmine; Sayed, Mohamed","year":2025,"journal":"BMC ophthalmology, 25(1), 518","doi":"10.1186/s12886-025-04322-2","pmid":"41029620","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11798","title":"A systematic review and meta-analysis comparing the cardiovascular effects of sodium-glucose co-transporter-2 inhibitors and glucagon-like peptide-1 agonists in type 2 diabetes.","authors":"Khan, Laibah Arshad; Sadia, Khudija; Naveed, Rahma; Khalid, Rehan; Faisal, Rabail; Bilal, Abdur Rafay; Nawaz, Ayeza; Safdar, Abdullah; Siddique, Talha Saleh Bin; Ahmad, Saleh Saeed; Hussain, Muhammad Ubaid; Asghar, Muhammad Talha; Ahmad, Wajdan","year":2025,"journal":"Journal of diabetes and metabolic disorders, 24(2), 221","doi":"10.1007/s40200-025-01741-2","pmid":"41084518","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11799","title":"Afadin Promotes Vascular Smooth Muscle Cell Contraction by Interacting With Phospholipase C to Enhance Ca2+ Signaling for Blood Pressure Regulation.","authors":"Khan, Md Mahbubur Rahman; Sato, Akira; Shimizu, Akio; Suetaka, Shunji; Molla, Md Rasel; Komeno, Masahiro; Nasrin, Mst Zenika; Nishida, Masanari; Toyoda, Futoshi; Arai, Munehito; Ogita, Hisakazu","year":2025,"journal":"Arteriosclerosis, thrombosis, and vascular biology, 45(7), 1226-1243","doi":"10.1161/ATVBAHA.125.322619","pmid":"40438927","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11800","title":"The clinical efficacy and safety of sodium-glucose co-transporter 2 inhibitors (SGLT2i) in patients with acute myocardial infarction: a meta-analysis of randomized controlled trials.","authors":"Khan, Muhammad Sami; Hashmi, Tallal Mushtaq; Jehangir, Hanzala; Akram, Muhammad Faiq; Munawar, Irja; Jagani, Sanjna Devi; Maqsood, Maham; Khalid, Ayesha; Ijaz, Maryam; Saeed, Usman; Jafar, Uzair; Ehsan, Muhammad; Tuglo, Lawrence Sena; Rehman, Wajeeh Ur; Sabouni, Mouhamed Amr; Braiteh, Nabil; Yarkoni, Alon; Patel, Keyoor","year":2025,"journal":"Annals of medicine and surgery (2012), 87(11), 7196-7205","doi":"10.1097/MS9.0000000000003724","pmid":"41180736","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11801","title":"From Gut to Brain: The roles of intestinal microbiota, immune system, and hormones in intestinal physiology and gut-brain-axis.","authors":"Khan, Muhammad Talha; Zohair, Muhammad; Khan, Areeba; Kashif, Ahmed; Mumtaz, Sadia; Muskan, Fiza","year":2025,"journal":"Molecular and cellular endocrinology, 607, 112599","doi":"10.1016/j.mce.2025.112599","pmid":"40482955","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11802","title":"The Role of Glucagon-Like Peptide-1 Receptor Agonists in Alcohol Use Disorder.","authors":"Khan, Sadaf; Sayana, Pavani; Waseem, Sarah; Oluwanifesimi, Olu-Lawal; Yadav, Garima; Mansuri, Zeeshan; Jain, Shailesh","year":2025,"journal":"The primary care companion for CNS disorders, 27(3)","doi":"10.4088/PCC.24nr03855","pmid":"40392538","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11803","title":"Antimicrobial Plant Peptides: Structure, Classification, Mechanism and Therapeutic Potential.","authors":"Khan, Shaina Shahab; Luqman, Suaib","year":2025,"journal":"Current topics in medicinal chemistry, 25(27), 3103-3156","doi":"10.2174/0115680266345963250121112522","pmid":"40103473","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies several key families of plant antimicrobial peptides:\n\n- Plant defensins — small cysteine-rich peptides with broad-spectrum antimicrobial activity\n- Thionins — toxic peptides that disrupt pathogen cell membranes\n- Cyclotides — exceptionally stable cyclic peptides with a wide range of biological activities\n\nTransgenic overexpression of AMP genes in plants increases pathogen resistance, while pathogen mutants susceptible to these peptides show decreased virulence — confirming the peptides' direct role in defense. The review emphasizes that plant AMPs exhibit activity against diverse pathogens and could serve as templates for new antimicrobial drugs for human use.","whyItMatters":"With antibiotic resistance growing worldwide, plant-derived antimicrobial peptides represent an underexplored reservoir of potential new therapeutics. Plants have evolved these defense molecules over hundreds of millions of years of pathogen exposure, resulting in highly effective and diverse antimicrobial strategies. Understanding these peptides could lead to novel drugs that work through mechanisms different from conventional antibiotics, potentially bypassing existing resistance.","specificNumbers":"","methodology":"This is a comprehensive review article surveying the published literature on plant antimicrobial peptides. The authors compiled information on AMP family classifications, three-dimensional structures, mechanisms of antimicrobial action, factors influencing activity, and evidence for therapeutic potential in pharmaceutical and medical applications.","limitations":"As a review article, this paper synthesizes existing research rather than presenting new experimental data. The therapeutic potential discussed is largely theoretical — most plant AMPs have not progressed to clinical trials in humans. Challenges including production scalability, potential toxicity to human cells, and pharmacokinetic properties (stability, bioavailability) are significant hurdles that are not fully addressed. The review covers a very broad topic, which may limit depth on any individual peptide family."},{"rthcId":"RPEP-11804","title":"Therapeutic efficacy of 4-hydroxyisoleucine in experimental rat model of demyelination: Neuroprotection through IGF-1 and GLP-1 level restoration.","authors":"Khan, Zuber; Mehan, Sidharth; Gupta, Ghanshyam Das","year":2025,"journal":"Phytomedicine : international journal of phytotherapy and phytopharmacology, 148, 157448","doi":"10.1016/j.phymed.2025.157448","pmid":"41187648","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11805","title":"Dosing Patterns of Dulaglutide and Semaglutide in Patients with Type 2 Diabetes Mellitus in France and Italy: A Retrospective Cohort Study.","authors":"Khare, Swarna; Osumili, Beatrice; Debackere, Nele; Keapoletswe, Karabo; Falato, Serena; Raoul, Thomas; Coles, Briana","year":2025,"journal":"Advances in therapy, 42(1), 174-192","doi":"10.1007/s12325-024-03002-9","pmid":"39487881","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11806","title":"Current developments and prospects of the antibiotic delivery systems.","authors":"Kharga, Kusum; Jha, Shubhang; Vishwakarma, Tanvi; Kumar, Lokender","year":2025,"journal":"Critical reviews in microbiology, 51(1), 44-83","doi":"10.1080/1040841X.2024.2321480","pmid":"38425122","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11807","title":"Long-Term Outcomes and Predictors of Recurrence in Atrial Arrhythmia Ablations Post-Fontan Procedure: A Retrospective Analysis.","authors":"Kharidia, Khush M; Tan, Weiyi; Patel, Nimesh S","year":2025,"journal":"Cardiology research, 16(2), 161-168","doi":"10.14740/cr2034","pmid":"40051672","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11808","title":"Weight Loss Efficacy of Tirzepatide Compared to Placebo or GLP-1 Receptor Agonists in Adults With Obesity or Overweight: A Meta-Analysis of Randomized Controlled Trials With ≥ 20 Weeks Treatment Duration.","authors":"Khawaji, Alhussain; A Jaly, Abdulaziz; A Bakri, Hanan; Ravi, Renju; Hattan, Ahmed; Khawaji, Abdullah; Najmi, Wael","year":2025,"journal":"Journal of obesity, 2025, 3442754","doi":"10.1155/jobe/3442754","pmid":"40746703","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11809","title":"Potential Drug Interaction Between Liraglutide and Clonazepam: A Case Report.","authors":"Kheradmand, Ali; Mehrvar, Amir; Abbasinazari, Mohammad","year":2025,"journal":"Case reports in psychiatry, 2025, 9100558","doi":"10.1155/crps/9100558","pmid":"39974287","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11810","title":"Targeting F2R/PAR1 with ligand decorated lipid nanocarriers for enhanced drug delivery into ovarian cancer cells.","authors":"Khetan, Riya; Rajapaksha, Weranga; Nturubika, Bukuru D; Gillam, Todd A; Brooks, Doug A; Garg, Sanjay; Blencowe, Anton; Albrecht, Hugo; Eldi, Preethi","year":2025,"journal":"Frontiers in drug delivery, 5, 1727958","doi":"10.3389/fddev.2025.1727958","pmid":"41608127","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11811","title":"Exendin-4 improves mitochondrial integrity against cisplatin-induced cardiac damage: Targeting p53 and NF-κB pathways.","authors":"Khine, Hnin Ei Ei; Mangmool, Supachoke; Parichatikanond, Warisara","year":2025,"journal":"European journal of pharmacology, 1007, 178233","doi":"10.1016/j.ejphar.2025.178233","pmid":"41075914","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11812","title":"Honokiol ameliorates reserpine-induced fibromyalgia through antioxidant, anti-inflammatory, neurotrophic, and anti-apoptotic mechanisms.","authors":"Khodir, Suzan A; Sweed, Eman M; El-Haroun, Hala; Abd-Elhamid, Tarek H; El Derbaly, Sara A; Mahmoud, Amany R; Motawea, Shaimaa M","year":2025,"journal":"Scientific reports, 15(1), 25983","doi":"10.1038/s41598-025-07209-w","pmid":"40676048","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11813","title":"New Contours, Different Risks: A 9-Year Comparison of Trends and Postoperative Complications in Patients Undergoing Aesthetic Surgery With Previous Bariatric Surgery Vs Glucagon-Like Peptide 1 Receptor Agonist Use.","authors":"Khong, Jeffrey; Suresh, Rachana; Park, Kitae E; Soltanian, Hooman","year":2025,"journal":"Aesthetic surgery journal, 45(11), 1159-1165","doi":"10.1093/asj/sjaf131","pmid":"40692274","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11814","title":"Neuropeptides, Altruism, and Adverse Childhood Experiences: Investigating Biological and Behavioral Correlations in Medical Students.","authors":"Khong, Jennifer; Bennett, Lauren; Felix Rivera, Johanna; Andrews, Nathan; Vuong, Veronica; Zapata, Demi; Khong, Phillip; Ryznar, Rebecca","year":2025,"journal":"Brain sciences, 15(10)","doi":"10.3390/brainsci15101128","pmid":"41154222","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11815","title":"Sublingual Delivery of Human GLP-1 Loaded Nanoliposomal Hydrogel for Treatment of Type 2 Diabetes Mellitus.","authors":"Khopade, Shivani; Agnihotri, Tejas Girish; Baviskar, Shraddha; Pavar, Bhaskar; Gomte, Shyam Sudhakar; Maskar, Tejas; Sharma, Nitish; Kumar, Hemant; Behera, Santosh Kumar; Jain, Aakanchha","year":2025,"journal":"AAPS PharmSciTech, 26(5), 155","doi":"10.1208/s12249-025-03152-1","pmid":"40461722","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11816","title":"Leveraging the htsFLT01/MiRGD Complex to Enhance Apoptosis and Suppress Angiogenesis in MCF7 Breast Cancer Cells.","authors":"Khoshandam, Mohadeseh; Soheili, Zahra-Soheila; Hosseinkhani, Saman; Samiee, Shahram; Latifi-Navid, Hamid; Kalhor, Naser; Soltaninejad, Hossein","year":2025,"journal":"Iranian journal of medical sciences, 50(10), 707-712","doi":"10.30476/ijms.2025.105176.3884","pmid":"41158839","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The htsFLT01/MiRGD nanocomplex, delivered at an optimal nitrogen-to-phosphorus (N/P) ratio of 14, successfully transfected MCF7 breast cancer cells and produced dual anti-cancer effects:\n\n1. Anti-angiogenic activity: The htsFLT01 gene encodes sFLT01 protein, which acts as a VEGF decoy receptor to block pathological blood vessel formation that tumors depend on for growth.\n\n2. Pro-apoptotic activity: Expression analysis revealed increased levels of FADD (Fas-Associated Death Domain Protein), CASP8 (Caspase-8), and TP53 (p53) — key genes in the extrinsic apoptotic pathway that triggers programmed cell death.\n\nThis dual mechanism suggests a synergistic relationship between blocking tumor blood supply and directly inducing cancer cell death.","whyItMatters":"Effective cancer gene therapy requires both a therapeutic gene and a safe, efficient delivery system. Peptide-based carriers like MiRGD offer advantages over viral vectors in terms of safety and biocompatibility. The finding that this system activates both anti-angiogenic and apoptotic pathways simultaneously could make it more effective than single-mechanism approaches.","specificNumbers":"","methodology":"The MiRGD peptide nanocarrier was expressed in E. coli and purified using Ni-NTA affinity chromatography. MCF7 breast cancer cells were transfected with the htsFLT01/MiRGD nanocomplex at an N/P ratio of 14 (previously optimized). Cell lysates were collected and analyzed for expression of apoptosis-related genes (FADD, CASP8, TP53) using gene expression analysis. Statistical analysis was performed using SPSS and REST 2009 software.","limitations":"This is an in vitro study using a single breast cancer cell line (MCF7), which may not represent the heterogeneity of breast cancers in patients. No in vivo experiments or animal models were used. The study builds heavily on prior work for construct design and nanocarrier optimization, making it difficult to assess as a standalone study. Specific fold-change values for gene expression increases are not reported in the abstract. No comparison with other delivery systems was included."},{"rthcId":"RPEP-11817","title":"Effect of Tirzepatide in an Adolescent With Early-Onset Obesity, Hyperphagia, and Type 2 Diabetes.","authors":"Khurshid, Bakht Noor; Moazzam, Ukasha; Dimitropoulos, Ioannis","year":2025,"journal":"Cureus, 17(10), e94770","doi":"10.7759/cureus.94770","pmid":"41113899","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11818","title":"Patient-Centered Outcomes in Heart Failure Pharmacotherapy: A Meta-Analysis of Randomized Controlled Trials.","authors":"Kido, Kazuhiko; Hashiguchi, Masayuki; Guglin, Maya","year":2025,"journal":"JACC. Advances, 4(12 Pt 2), 102356","doi":"10.1016/j.jacadv.2025.102356","pmid":"41447282","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 or GLP-1/GIP agonists significantly improved both KCCQ quality of life scores and 6-minute walking distance compared to placebo in heart failure patients. IV iron was the only other therapy to achieve improvements on both outcomes.\n\nSGLT2 inhibitors improved KCCQ scores but not 6-minute walking distance. MRA, ARNI, vericiguat, and ivabradine showed no significant differences in KCCQ scores versus placebo/control. Beta-blockers, ARNI, MRA, SGLT2 inhibitors, and ivabradine showed no significant improvement in 6-minute walking distance.","whyItMatters":"Heart failure treatment has traditionally focused on mortality and hospitalization reduction. But patients often rank feeling better and being able to exercise as equally or more important. This meta-analysis reveals a striking gap: many drugs that save lives don't measurably improve how patients feel day-to-day. GLP-1 agonists' ability to improve both quality of life and functional capacity adds a compelling patient-centered argument for their use in heart failure.","specificNumbers":"","methodology":"Meta-analysis of randomized controlled trials in ambulatory (outpatient) heart failure. Eight drug classes were analyzed: IV iron, beta-blockers, SGLT2 inhibitors, ARNI, MRA, vericiguat, ivabradine, and GLP-1/GIP agonists. Co-primary outcomes were KCCQ scores (quality of life) and 6-minute walking distance (exercise capacity).","limitations":"The meta-analysis combines trials with different heart failure populations, definitions, and treatment durations. KCCQ and 6MWD may not have been primary outcomes in the underlying trials, potentially introducing reporting bias. The number of GLP-1/GIP agonist trials in heart failure is still relatively small compared to established drug classes. The analysis does not account for differences in mortality benefit across drug classes."},{"rthcId":"RPEP-11819","title":"Complete Resolution of New Daily Persistent Headache With Migraine-Like Features Following Erenumab Treatment: A Case Report.","authors":"Kikui, Shoji; Danno, Daisuke; Takeshima, Takao","year":2025,"journal":"Cureus, 17(5), e84442","doi":"10.7759/cureus.84442","pmid":"40539136","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11820","title":"The Role of Cardiac Biomarkers in Evaluating Takotsubo Cardiomyopathy: A Systematic Review.","authors":"Kilaru, Pranavi; Kilaru, Pranati; Garikipaty, Shreya","year":2025,"journal":"Cureus, 17(6), e86168","doi":"10.7759/cureus.86168","pmid":"40677457","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11821","title":"Determinants of Improved CGRP Peptide Binding Kinetics Revealed by Enhanced Molecular Simulations.","authors":"Kilinc, Ceren; Babin, Katie M; Pioszak, Augen A; Dickson, Alex","year":2025,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2025.06.13.659569","pmid":"40667178","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11822","title":"Development of recombinant Mesozumab-CPTin that dual-targets mesothelin and CP2c for anticancer therapy.","authors":"Kim, Boram; Byun, Kyu Tae; Cho, Junmin; Lee, Inbeom; Park, DongSun; Kang, Tae-Bong; Won, Hyung-Sik; Cheon, So Yeong; Kim, Chan Gil","year":2025,"journal":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 193, 118799","doi":"10.1016/j.biopha.2025.118799","pmid":"41270471","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11823","title":"Recent Advances in Functionalized Nanoparticles for Targeted and Controlled Inner Ear Therapy via Localized Cochlear Delivery.","authors":"Kim, Dong-Kee","year":2025,"journal":"Journal of audiology & otology, 29(3), 159-165","doi":"10.7874/jao.2025.00311","pmid":"40739932","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11824","title":"Animal Venom in Modern Medicine: A Review of Therapeutic Applications.","authors":"Kim, Euikyung; Hwang, Du Hyeon; Mohan Prakash, Ramachandran Loganathan; Asirvatham, Ravi Deva; Lee, Hyunkyoung; Heo, Yunwi; Munawir, Al; Seyedian, Ramin; Kang, Changkeun","year":2025,"journal":"Toxins, 17(8)","doi":"10.3390/toxins17080371","pmid":"40864047","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11825","title":"SeqDA-HLA: Language Model and Dual Attention-Based Network to Predict Peptide-HLA Class I Binding.","authors":"Kim, Gihyeon; Jo, Geonhui; Kim, Minjeong; Cho, Soo Young; Choi, Jang-Hwan","year":2025,"journal":"IEEE transactions on computational biology and bioinformatics, 22(6), 3153-3163","doi":"10.1109/TCBBIO.2025.3614457","pmid":"40996987","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"SeqDA-HLA achieved an AUC of up to 0.9856 and accuracy as high as 94.08% on benchmark datasets, outperforming 14 state-of-the-art methods for peptide-HLA class I binding prediction. The model maintained strong performance across peptide lengths ranging from 8 to 14 amino acids and across diverse HLA alleles.\n\nBeyond prediction accuracy, the model provides interpretable results by highlighting anchor residues and binding motifs that align with experimentally validated biological findings. When fine-tuned on an Influenza virus dataset, it successfully predicted how single amino acid mutations affect binding.","whyItMatters":"Accurately predicting which peptides bind to HLA molecules is a bottleneck in developing personalized cancer vaccines and immunotherapies. A more accurate and interpretable prediction tool like SeqDA-HLA could speed up the identification of therapeutic targets and help design more effective treatments for cancer and infectious diseases.","specificNumbers":"","methodology":"The researchers built a deep learning model combining ELMo language model embeddings with a dual attention mechanism (self-aligned cross-attention and self-attention) to capture contextual features and interactions between peptides and HLA molecules. They benchmarked SeqDA-HLA against 14 existing prediction methods on multiple established datasets, testing performance across varying peptide lengths and HLA alleles. They also fine-tuned the model on Influenza virus data to demonstrate practical applicability.","limitations":"The study is computational and has not been validated in wet-lab experiments or clinical settings. Benchmark dataset performance may not fully reflect real-world complexity, particularly for rare HLA alleles or unusual peptide modifications. The model's utility for clinical decision-making remains to be demonstrated in prospective studies."},{"rthcId":"RPEP-11826","title":"Healthcare Utilization, Costs, and Treatment Discontinuation in Adults with Episodic Migraine Initiating Galcanezumab Versus Rimegepant: A US Retrospective Claims Analysis.","authors":"Kim, Gilwan; Hoyt, Margaret; Zakharyan, Armen; Durica, Jennifer; Wallem, Alexandra; Viktrup, Lars","year":2025,"journal":"Advances in therapy, 42(2), 918-934","doi":"10.1007/s12325-024-03072-9","pmid":"39680312","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Over 12 months of follow-up using propensity score-matched cohorts, galcanezumab users had significantly lower cost increases than rimegepant users: 21% lower increase in all-cause total medical and pharmacy costs, and 76% lower increase in migraine-related total costs.\n\nTreatment persistence was also notably better with galcanezumab. The median time to discontinuation (using a >60-day gap definition) was 244.6 days for galcanezumab versus 178.1 days for rimegepant. Galcanezumab users were 1.8 times less likely to discontinue treatment (HR = 1.81, 95% CI: 1.56–2.10, p < 0.0001).","whyItMatters":"Migraine prevention medications targeting the CGRP pathway are relatively new, and clinicians and patients need real-world data to guide treatment choices. This is the first head-to-head comparison of these two specific therapies, providing practical insights into which option leads to lower healthcare costs and better treatment adherence — factors that directly impact long-term migraine management success.","specificNumbers":"","methodology":"This retrospective claims analysis used the Merative MarketScan Research Databases from June 2020 to June 2023. Adults with episodic migraine were grouped by whether they initiated galcanezumab or rimegepant. Cohorts were propensity score-matched to balance baseline characteristics. Healthcare utilization, costs, and treatment discontinuation were compared over 12 months using Wilcoxon signed rank tests, chi-square tests, Kaplan-Meier analysis, and Cox proportional hazards models.","limitations":"As a retrospective claims analysis, the study cannot establish causation or account for all confounding factors despite propensity score matching. Claims data cannot capture clinical outcomes like migraine frequency reduction. The study was funded by Eli Lilly, the manufacturer of galcanezumab, which may introduce bias. The rimegepant cohort required a quantity threshold of ≥15, which may affect comparability. Clinical effectiveness differences were not directly measured."},{"rthcId":"RPEP-11827","title":"Comparative analysis of LJ-4378 and tirzepatide in mouse models of obesity and weight regain.","authors":"Kim, Heeseong; Kim, Seung Woo; Choi, Cheoljun; Joo, SungUg; Kim, Gibae; Kim, Minjae; Yang, Eunsuk; Lee, Jangwon; Chung, Sukjae; Jeong, Lak Shin; Lee, Yun-Hee","year":2025,"journal":"Archives of pharmacal research, 48(11-12), 1441-1459","doi":"10.1007/s12272-025-01575-9","pmid":"41199017","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11828","title":"Real-World Evidence of Long-Term Dulaglutide Use: Sustained Glycemic and Weight Improvements Beyond Three Years.","authors":"Kim, Hwi Seung; Kim, Myung Jin; Kim, Hee Sung; Cho, Yun Kyung; Jung, Chang Hee; Lee, Woo Je","year":2025,"journal":"Clinical endocrinology","doi":"10.1111/cen.70078","pmid":"41387176","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11829","title":"Combination of Citrus aurantifolia Fruit Rind and Theobroma cacao Seed Extracts Stimulates Glucagon-Like Peptide-1 Secretion by Activating hTAS2Rs and the Phospholipase C-Mediated Signaling Pathway in NCI-H716 Cells.","authors":"Kim, Hyunjae; Park, Soyoon; Ahn, Hye Shin; Na, Changseon; Shin, Yu-Kyong","year":2025,"journal":"Preventive nutrition and food science, 30(5), 467-473","doi":"10.3746/pnf.2025.30.5.467","pmid":"41180086","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11830","title":"Comparative Pharmacological and Pharmaceutical Perspectives on Antidiabetic Therapies in Humans, Dogs, and Cats.","authors":"Kim, Iljin; Yun, Jang-Hyuk","year":2025,"journal":"Pharmaceutics, 17(9)","doi":"10.3390/pharmaceutics17091098","pmid":"41012437","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11831","title":"Heart failure with preserved ejection fraction: current insights and emerging therapeutic directions.","authors":"Kim, Jeehyun; Eom, GwangHyeon; Yoon, Somy","year":2025,"journal":"The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology","doi":"10.4196/kjpp.25.250","pmid":"41340488","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11832","title":"Solitary phospholipase C β2-positive cells in the vomeronasal organs of Korean roe deer (Capreolus pygargus).","authors":"Kim, Jeongtae; Jung, Kyungsook; Ortiz-Leal, Irene; Sanchez-Quinteiro, Pablo; Ahn, Meejung; Shin, Taekyun","year":2025,"journal":"The Journal of veterinary medical science, 87(10), 1176-1179","doi":"10.1292/jvms.24-0534","pmid":"40903304","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11833","title":"Glucagon-like peptide-1 receptor agonists and mental health: a narrative review of emerging benefits and risks.","authors":"Kim, JinWoo","year":2025,"journal":"Journal of Yeungnam medical science, 42, 61","doi":"10.12701/jyms.2025.42.61","pmid":"41025359","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies a nuanced psychiatric profile for GLP-1 receptor agonists:\n\n**Positive evidence:**\n- Substance use disorders: consistent evidence for therapeutic benefit, particularly for alcohol use disorders\n- Dementia: several cohort studies indicate reduced risk, suggesting neuroprotective effects\n\n**Mixed evidence:**\n- Depression and anxiety: conflicting results from large observational studies, largely due to confounding by indication and methodological differences\n\n**Safety concerns addressed:**\n- Suicidality: initial reports raised alarm, but well-controlled active-comparator studies found no increased risk. Initial findings were likely driven by methodological limitations\n- Safety in high-risk psychiatric populations: not yet established\n\nThe overall profile suggests therapeutic potential but calls for caution in psychiatrically vulnerable patients.","whyItMatters":"With GLP-1 drugs prescribed to an unprecedented number of patients for diabetes and obesity, understanding their psychiatric effects is critical. The finding that these drugs may help with alcohol addiction could open a major new therapeutic avenue. Equally important is resolving the suicidality question — unfounded safety concerns could prevent patients from accessing beneficial treatment, while real risks in vulnerable populations must be identified and managed.","specificNumbers":"","methodology":"This is a narrative review summarizing current evidence on GLP-1 RAs' effects on psychiatric and neurocognitive conditions. The author evaluated observational studies, cohort studies, active-comparator analyses, and regulatory safety data across multiple mental health domains.","limitations":"This is a narrative review, not a systematic review or meta-analysis, which may introduce selection bias. Much of the psychiatric evidence comes from observational studies with significant confounding factors — people taking GLP-1 drugs for diabetes/obesity differ systematically from controls. The conflicting depression/anxiety data may reflect that some patients improve (via weight loss-related quality of life) while others worsen (via biological mechanisms), making average effects misleading. Long-term psychiatric follow-up data are lacking."},{"rthcId":"RPEP-11834","title":"Mechanisms of glucagon-like-peptide 1 in the brain beyond metabolic effects.","authors":"Kim, Kyu Sik; Park, Joon Seok; Choi, Hyung Jin","year":2025,"journal":"Annals of pediatric endocrinology & metabolism, 30(4), 165-174","doi":"10.6065/apem.2448320.160","pmid":"40916127","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11835","title":"Use of Glucagon-Like Peptide-1 Receptor Agonists Does Not Increase the Risk of Cancer in Patients with Type 2 Diabetes Mellitus.","authors":"Kim, Mijin; Kim, Seung Chan; Kim, Jinmi; Kim, Bo Hyun","year":2025,"journal":"Diabetes & metabolism journal, 49(1), 49-59","doi":"10.4093/dmj.2024.0105","pmid":"39443282","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11836","title":"Transformer-based models for ADR detection: cross-drug validation and benchmarking against large language models.","authors":"Kim, Minjung; Kim, Kyoung Eun; Kwon, Jae-Hee; Han, Ja-Young; Kim, Jae Hyun; Kim, Myeong Gyu","year":2025,"journal":"Therapeutic advances in drug safety, 16, 20420986251405082","doi":"10.1177/20420986251405082","pmid":"41426306","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11837","title":"ATP stimulates appetite by enhancing the expression of hypothalamic orexigenic neuropeptides.","authors":"Kim, Nayoun; Kim, Eun-Kyoung","year":2025,"journal":"Molecular brain, 18(1), 49","doi":"10.1186/s13041-025-01220-y","pmid":"40495207","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11838","title":"Antimicrobial Peptides: Current Status, Mechanisms of Action, and Strategies to Overcome Therapeutic Limitations.","authors":"Kim, Seong Hwan; Min, Yu-Hong; Park, Min Chul","year":2025,"journal":"Microorganisms, 13(11)","doi":"10.3390/microorganisms13112574","pmid":"41304259","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11839","title":"Peptide mapping analysis of synthetic semaglutide and liraglutide for generic development of drugs originating from recombinant DNA technology.","authors":"Kim, Soo Hyun; Kim, Sung Soo; Kim, Hyun Jun; Park, Eun Ji; Na, Dong Hee","year":2025,"journal":"Journal of pharmaceutical and biomedical analysis, 256, 116682","doi":"10.1016/j.jpba.2025.116682","pmid":"39847923","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11840","title":"Combinatorial strategy for engineering cartilage and bone microtissues using microfluidic cell-laden microgels.","authors":"Kim, Suntae; Li, Siyuan; Baek, Seung Yeop; Cha, Chaenyung; Lee, Sang Jin","year":2025,"journal":"Biofabrication, 17(3)","doi":"10.1088/1758-5090/adc840","pmid":"40174602","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11841","title":"Adverse drug reaction patterns of GLP-1 receptor agonists approved for obesity treatment: Disproportionality analysis from global pharmacovigilance database.","authors":"Kim, Tae Hyeon; Lee, Kyeongmin; Park, Seoyoung; Oh, Jiyeon; Park, Jaeyu; Jo, Hyesu; Lee, Hayeon; Cho, Jaehyeong; Wen, Xuerong; Cho, Hanseul; Kim, Sunyoung; Yon, Dong Keon","year":2025,"journal":"Diabetes, obesity & metabolism, 27(6), 3490-3502","doi":"10.1111/dom.16376","pmid":"40176478","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11842","title":"Disproportionality analysis of infection associated with antidiabetic drug use patterns.","authors":"Kim, Tae Hyeon; Lee, Kyeongmin; Park, Seoyoung; Park, Jaeyu; Jo, Hyesu; Lee, Hayeon; Kim, Hyunjee; Cho, Jaehyeong; Rhee, Sang Youl; Hajek, André; Branda, Francesco; Song, Tae-Jin; Kim, Jaewon; Yon, Dong Keon","year":2025,"journal":"Scientific reports, 15(1), 33583","doi":"10.1038/s41598-025-18723-2","pmid":"41023271","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11843","title":"Retrospective Study of Real-World Treatment Patterns of Subcutaneous Semaglutide Use Among Patients with Metabolic Dysfunction-Associated Steatohepatitis in the United States.","authors":"Kim, Yestle; Zeng, Ni; Winer-Jones, Jessamine P; Bonafede, Machaon; Lobo, Francis; O'Donnell, John; Ryan, Taylor","year":2025,"journal":"ClinicoEconomics and outcomes research : CEOR, 17, 743-754","doi":"10.2147/CEOR.S546841","pmid":"41147033","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11844","title":"Transcriptomics of SGLT2-positive early proximal tubule segments in mice: response to type 1 diabetes, SGLT1/2 inhibition, or GLP1 receptor agonism.","authors":"Kim, Young Chul; Das, Vivek; Kanoo, Sadhana; Yao, Huazhen; Stanford, Stephanie M; Bottini, Nunzio; Karihaloo, Anil; Vallon, Volker","year":2025,"journal":"American journal of physiology. Renal physiology, 328(1), F68-F81","doi":"10.1152/ajprenal.00231.2024","pmid":"39589189","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11845","title":"Metabolic imbalance and brain tumors: The interlinking metabolic pathways and therapeutic actions of antidiabetic drugs.","authors":"Kim, Young-Kook; Song, Juhyun","year":2025,"journal":"Pharmacological research, 215, 107719","doi":"10.1016/j.phrs.2025.107719","pmid":"40174814","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review synthesizes evidence showing that metabolic syndrome features (hyperglycemia, insulin resistance, oxidative stress, altered adipokines) promote brain tumor growth, proliferation, and treatment resistance. GLP-1 receptor agonists and DPP-4 inhibitors target both metabolic and inflammatory aspects of brain tumors. Metformin activates AMPK and inhibits mTOR to impair tumor proliferation. Thiazolidinediones can induce tumor cell apoptosis and synergize with other therapies. All these approaches represent potential drug repurposing strategies.","whyItMatters":"Brain tumors, particularly glioblastoma, have limited treatment options and extremely poor prognosis. If existing antidiabetic drugs — already proven safe for long-term use — can be repurposed as adjunctive brain tumor therapies, this could rapidly expand the treatment toolkit. The metabolic reprogramming that tumor cells undergo makes metabolic interventions a rational strategy, and drugs like GLP-1RAs that cross the blood-brain barrier are particularly relevant.","specificNumbers":"","methodology":"Narrative review examining evidence for metabolic connections between diabetes/metabolic syndrome and brain tumors, and evaluating preclinical and clinical evidence for antidiabetic drug efficacy against brain tumors.","limitations":"This is a narrative review with most evidence from preclinical studies and observational data. No randomized clinical trials of GLP-1RAs or DPP-4 inhibitors specifically for brain tumors have been published. The mechanisms described are largely demonstrated in cell culture and animal models. Extrapolating from diabetes-related metabolic effects to antitumor efficacy is speculative. Different brain tumor types may respond very differently to metabolic interventions."},{"rthcId":"RPEP-11846","title":"Evaluating the association between migraine treatments and tinnitus: Insights from the US Food and Drug Administration adverse event reporting system.","authors":"Kim, Yun; Yook, Yeabin; Rhee, Su-Jin","year":2025,"journal":"PloS one, 20(8), e0330493","doi":"10.1371/journal.pone.0330493","pmid":"40833961","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11847","title":"A Dual-Target-Based Screening Strategy for Anti-SARS-CoV-2 Active Compounds Enabling the Identification of Macrocyclic Peptide Natural Products: Chloropeptins.","authors":"Kimishima, Aoi; Ikeda, Terumasa; Takahashi, Otowa; Naher, Kamrun; Watanabe, Chiduru; Takai-Todaka, Reiko; Haga, Kei; Honma, Sota; Ujie, Yukiko; Uematsu, Takayuki; Honsho, Masako; Sunazuka, Toshiaki; Honma, Teruki; Katayama, Kazuhiko; Asami, Yukihiro","year":2025,"journal":"Journal of natural products, 88(10), 2351-2359","doi":"10.1021/acs.jnatprod.5c00634","pmid":"40998293","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11848","title":"Radiation-induced transformation of peptides into nanoparticles for nano-theranostics of pancreatic cancer with controllable drug delivery and sustained release.","authors":"Kimura, Atsushi; Hamaguchi, Hiroki; Oyama, Kotaro; Tian, Chaozhong; Yamashita, Shinichi; Taguchi, Mitsumasa","year":2025,"journal":"Free radical research, 59(10-12), 769-782","doi":"10.1080/10715762.2025.2580607","pmid":"41170884","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11849","title":"An acute aortic dissection prognostic score for predicting early in-hospital mortality in acute thoracic aortic dissection.","authors":"Kimura, Satoshi; Sato, Hiroaki; Shimajiri, Shohei; Nakayama, Toshiyuki","year":2025,"journal":"American heart journal plus : cardiology research and practice, 52, 100521","doi":"10.1016/j.ahjo.2025.100521","pmid":"40129616","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11850","title":"Effect of glucagon-like peptide-1 receptor agonists on vascular risk factors among adults with type 2 diabetes and established atherosclerotic cardiovascular disease.","authors":"King, Aaron; Tan, Xi; Dhopeshwarkar, Neil; Bohn, Rhonda; Dea, Katherine; Leonard, Charles E; de Havenon, Adam","year":2025,"journal":"American journal of preventive cardiology, 21, 100922","doi":"10.1016/j.ajpc.2024.100922","pmid":"39896054","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11851","title":"GLP-1 RA Medication Associations With Hazardous Alcohol Drinking Reductions in Patients With Overweight or Obesity: A Prospective Observational Study.","authors":"King, Andrea C; Wellendorf, Claire; Atkinson, Emily A; de Carvalho, Maria Eduarda Amaral; Fridberg, Daniel J; Pannain, Silvana","year":2025,"journal":"Journal of addiction medicine","doi":"10.1097/ADM.0000000000001565","pmid":"40792626","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Fourteen patients with overweight/obesity and hazardous drinking (AUDIT score ≥8) were prescribed GLP-1 RAs (semaglutide n=8, tirzepatide n=5, liraglutide n=1) alongside standard dietary and exercise counseling. After a mean of 9.6 months of treatment, both BMI and AUDIT scores decreased significantly.\n\nPatients in the 'very high' AUDIT group (score ≥15) showed more pronounced reductions in drinking scores compared to those in the 'high' group (score 8-14). Effect sizes were large, indicating a substantial magnitude of the GLP-1 RA effect on hazardous drinking behavior.","whyItMatters":"Anecdotal reports and animal studies have suggested GLP-1 drugs reduce alcohol cravings and consumption, but prospective human data has been limited. This study provides early clinical evidence that GLP-1 receptor agonists may have clinically meaningful effects on hazardous drinking — potentially opening an entirely new therapeutic application for these peptide drugs beyond diabetes and obesity. With alcohol use disorder affecting millions and having limited pharmacotherapy options, this is a significant finding.","specificNumbers":"","methodology":"Prospective observational study at the University of Chicago Weight Loss Clinic. Patients prescribed GLP-1 RAs for overweight/obesity were screened for hazardous drinking using the AUDIT (Alcohol Use Disorders Identification Test). Those scoring ≥8 were enrolled and reassessed after approximately 9.6 months of treatment. BMI and AUDIT scores were compared pre- and post-treatment.","limitations":"This is a very small observational study (n=14) without a control group, so improvements could be partly attributable to the clinical setting, dietary counseling, or natural fluctuation in drinking patterns. Patients were not specifically seeking alcohol treatment, which may introduce selection bias. The AUDIT is a self-report measure subject to social desirability bias. Different GLP-1 drugs were used, making it impossible to determine drug-specific effects. Randomized controlled trials are needed."},{"rthcId":"RPEP-11852","title":"Group size influences feeding behavior and the expression of appetite, stress, and neurotransmitter-related transcript expression in tiger barb (Puntigrus tetrazona).","authors":"King, Julianne M D; Volkoff, Helene","year":2025,"journal":"Comparative biochemistry and physiology. Part A, Molecular & integrative physiology, 308, 111915","doi":"10.1016/j.cbpa.2025.111915","pmid":"40752566","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11853","title":"Evaluation of antimicrobial and antibiofilm efficacy of different antimicrobial peptides on multispecies biofilm of endodontic pathogens.","authors":"Kini, Shravan; Shetty, K Harish; Ballal, Nidambur Vasudev; Bhat, Kishore G; Ingalagi, Preeti","year":2025,"journal":"Journal of conservative dentistry and endodontics, 28(12), 1215-1221","doi":"10.4103/JCDE.JCDE_706_25","pmid":"41438437","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11854","title":"Identification of 68 HLA-A24 and -A2-restricted cytotoxic T lymphocyte-inducing peptides derived from 10 common cancer-specific antigens frequently expressed in various solid cancers.","authors":"Kinoshita, Hiroki; Takenouchi, Kazumasa; Tsukamoto, Nobuo; Ohnuki, Kazunobu; Suzuki, Toshihiro; Nakatsura, Tetsuya","year":2025,"journal":"Neoplasia (New York, N.Y.), 61, 101135","doi":"10.1016/j.neo.2025.101135","pmid":"39938154","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11855","title":"Revisiting the potential of natural antimicrobial peptides against emerging respiratory viral disease: a review.","authors":"Kiran, Neelakanta Sarvashiva; Singh, Sudarshan; Yashaswini, Chandrashekar; Prajapati, Bhupendra G","year":2025,"journal":"3 Biotech, 15(2), 40","doi":"10.1007/s13205-024-04184-3","pmid":"39816617","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11856","title":"Association of Glucagon-like Peptide-1 Receptor Agonist Use with Complications Following Thoracic and/or Lumbar Spinal Fusion for Degenerative Spine Disease: A BMI-Stratified Retrospective Study.","authors":"Kishan, Arman; Khela, Harmon S; Carayannopoulos, Nicolas L; Singh, Manjot; Cohen, Lara; Chisango, Zvipo; Chatzis, Kyriakos; Tretiakov, Peter S; Vira, Shaleen; Jankowski, Pawel P; Schoenfeld, Andrew J; Passias, Peter G; Daniels, Alan H","year":2025,"journal":"Spine","doi":"10.1097/BRS.0000000000005494","pmid":"40905270","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11857","title":"An ensemble learning model for detection of pulmonary hypertension using electrocardiogram, chest X-ray, and brain natriuretic peptide.","authors":"Kishikawa, Risa; Kodera, Satoshi; Setoguchi, Naoto; Tanabe, Kengo; Kushida, Shunichi; Nanasato, Mamoru; Maki, Hisataka; Fujita, Hideo; Kato, Nahoko; Watanabe, Hiroyuki; Takahashi, Masao; Sawada, Naoko; Ando, Jiro; Sato, Masataka; Sawano, Shinnosuke; Shinohara, Hiroki; Nakanishi, Koki; Minatsuki, Shun; Ishida, Junichi; Fujiu, Katsuhito; Akazawa, Hiroshi; Morita, Hiroyuki; Takeda, Norihiko","year":2025,"journal":"European heart journal. Digital health, 6(2), 209-217","doi":"10.1093/ehjdh/ztae097","pmid":"40110214","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11858","title":"Cardiovascular outcomes and safety of semaglutide in non-overweight populations with type 2 diabetes: a comparison with dipeptidyl peptidase 4 inhibitors.","authors":"Kishimori, Takefumi; Kato, Takao; Wada, Atsuyuki; Tani, Akira; Yamaji, Ryosuke; Koike, Jumpei; Iwasaki, Yoshihiro; Matsumoto, Takehiro; Yagi, Takafumi; Okada, Masaharu","year":2025,"journal":"European heart journal. Quality of care & clinical outcomes, 11(8), 1319-1328","doi":"10.1093/ehjqcco/qcaf065","pmid":"40676725","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11859","title":"Combination therapy with sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists in heart failure patients with type 2 diabetes.","authors":"Kishimori, Takefumi; Kato, Takao; Wada, Atsuyuki; Tani, Akira; Yamaji, Ryosuke; Koike, Jumpei; Iwasaki, Yoshihiro; Matsumoto, Takahiro; Yagi, Takafumi; Okada, Masaharu","year":2025,"journal":"BMJ open diabetes research & care, 13(6)","doi":"10.1136/bmjdrc-2025-005364","pmid":"41192940","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"After propensity score matching (23,240 patients per group), combining SGLT2 inhibitors with GLP-1 receptor agonists versus SGLT2 inhibitor monotherapy produced:\n\n- All-cause death: 2.8% vs 6.3% (HR 0.43, 95% CI 0.39-0.48, p<0.001) — a 57% relative risk reduction\n- Hospitalization: 32.9% vs 36.4% (HR 0.87, 95% CI 0.84-0.90, p<0.001) — a 13% relative risk reduction\n\nThese results were observed over a 1-year follow-up period in patients with both heart failure and type 2 diabetes.","whyItMatters":"Heart failure with diabetes is a devastating combination with very high mortality. While each drug class individually reduces cardiovascular risk, this study provides some of the first large-scale evidence that combining them yields dramatically better survival. A 57% reduction in death risk is a remarkable finding that could change how clinicians approach this common patient population.","specificNumbers":"","methodology":"Multicenter retrospective observational study using the TriNetX database (January 2018 – December 2021). From 928,981 patients with heart failure and type 2 diabetes, 168,422 received an SGLT2 inhibitor. The combination group initiated a GLP-1 RA within 6 months of starting an SGLT2i. Propensity score matching yielded 23,240 patients per group. Outcomes (all-cause death, hospitalization) were assessed over 1 year.","limitations":"This is a retrospective observational study, so it cannot establish causation. Despite propensity score matching, residual confounding is possible — patients receiving combination therapy may have been healthier or had better healthcare access. The 57% mortality reduction is larger than typically seen in randomized trials, suggesting possible selection bias. The TriNetX database may not capture all relevant clinical variables. No differentiation was made between specific GLP-1 RAs or SGLT2is."},{"rthcId":"RPEP-11860","title":"Comparative cardiovascular outcomes of semaglutide to dulaglutide in patients with type 2 diabetes.","authors":"Kishimori, Takefumi; Kato, Takao; Wada, Atsuyuki; Tani, Akira; Yamaji, Ryosuke; Koike, Jumpei; Iwasaki, Yoshihiro; Matsumoto, Takehiro; Yagi, Takafumi; Okada, Masaharu","year":2025,"journal":"Scientific reports, 15(1), 21333","doi":"10.1038/s41598-025-06245-w","pmid":"40594279","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11861","title":"Effectiveness of semaglutide on survival outcomes in patients with type 2 diabetes and chronic kidney disease.","authors":"Kishimori, Takefumi; Kato, Takao; Wada, Atsuyuki; Tani, Akira; Yamaji, Ryosuke; Koike, Jumpei; Iwasaki, Yoshihiro; Matsumoto, Takehiro; Yagi, Takafumi; Okada, Masaharu","year":2025,"journal":"Open heart, 12(2)","doi":"10.1136/openhrt-2025-003382","pmid":"40628673","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11862","title":"Efficacy and safety of rimegepant for the preventive treatment of migraine in Japan: A double-blind, randomized controlled trial.","authors":"Kitamura, Shigekazu; Matsumori, Yasuhiko; Yamamoto, Toshimasa; Ishikawa, Tomofumi; Hoshino, Yuko; Yoshimatsu, Hiroki; Thiry, Alexandra; Arakawa, Akio; Croop, Robert; Fullerton, Terence; Sakai, Fumihiko; Takeshima, Takao","year":2025,"journal":"Headache, 65(8), 1403-1412","doi":"10.1111/head.14995","pmid":"40542538","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11863","title":"The Effects of Oral Semaglutide on Hepatic Fibrosis in Subjects with Type 2 Diabetes in Real-World Clinical Practice: A Post Hoc Analysis of the Sapporo-Oral SEMA Study.","authors":"Kitsunai, Hiroya; Shinozaki, Yuka; Furusawa, Sho; Kitao, Naoyuki; Ito, Miki; Kurihara, Hiroyoshi; Oba-Yamamoto, Chiho; Takeuchi, Jun; Nakamura, Akinobu; Takiyama, Yumi; Nomoto, Hiroshi","year":2025,"journal":"Pharmaceuticals (Basel, Switzerland), 18(1)","doi":"10.3390/ph18010129","pmid":"39861190","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11864","title":"Tear deficiency transforms spatial distribution of corneal calcitonin gene-related peptide-positive nerves in rats.","authors":"Kiyoi, Takeshi; Nakajima, Akihiro; He, Qiang; Liu, Li; Zheng, Shijie; Kobayashi, Shizuka; Uwada, Junsuke; Masuoka, Takayoshi","year":2025,"journal":"Frontiers in cellular neuroscience, 19, 1619310","doi":"10.3389/fncel.2025.1619310","pmid":"40666279","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11865","title":"Efficacy of the Glucagon-Like Peptide-1 Agonist Exenatide in Patients Undergoing CABG or Aortic Valve Replacement: A Randomized Double-Blind Clinical Trial.","authors":"Kjaergaard, Jesper; Møller, Christian Holdflod; Wiberg, Sebastian; Mikkelsen, Astrid Duus; Møller-Sørensen, Hasse; Ravn, Hanne Berg; Ravn, Jesper; Olsen, Peter Skov; Høfsten, Dan E; Boesgaard, Søren; Køber, Lars; Nilsson, Jens Christian; Hassager, Christian","year":2025,"journal":"Circulation. Cardiovascular interventions, 18(5), e014961","doi":"10.1161/CIRCINTERVENTIONS.124.014961","pmid":"40265262","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In this randomized, double-blind clinical trial of 1,389 predominantly low-risk patients undergoing elective coronary artery bypass grafting or aortic valve replacement:\n\n- 170 patients (24%) in the exenatide group and 165 patients (24%) in the placebo group experienced the primary composite endpoint (death, stroke, renal failure requiring dialysis, or new/worsening heart failure)\n- No significant difference in time to first event between groups\n- No significant difference in rates of adverse events\n- Median follow-up was 5.9 years (range 2.5–8.3 years)\n- The study also tested liberal vs. restrictive oxygenation during bypass in a 2×2 factorial design, finding no difference there either (HR 1.0; 95% CI 0.83–1.3; p = 0.80)\n\nExenatide was administered as a 17.4 µg infusion during cardiopulmonary bypass and for the first hour after weaning from bypass.","whyItMatters":"This is an important negative result. While GLP-1 agonists have demonstrated cardiovascular benefits in diabetes and obesity trials, this study shows those benefits don't extend to acute perioperative cardioprotection during bypass surgery. This helps define the boundaries of GLP-1 drugs' cardiovascular effects and prevents unnecessary adoption of an ineffective intervention in cardiac surgery.","specificNumbers":"","methodology":"This was a randomized, double-blind, single-center clinical trial with a 2×2 factorial design. Adult patients undergoing elective cardiopulmonary bypass-assisted CABG or aortic valve replacement were randomized to receive either exenatide (17.4 µg infusion) or placebo during bypass and the first hour post-bypass, and to either liberal (100% FiO2) or restrictive (50% FiO2) oxygenation. The primary outcome was a composite of death, stroke, renal failure requiring dialysis, or new/worsening heart failure. Follow-up extended to a median of 5.9 years.","limitations":"The study enrolled predominantly low-risk elective surgery patients, which may have limited the ability to detect benefit in a population with a low event rate. The exenatide infusion was given only during and briefly after bypass — a short exposure window that may be insufficient. Single-center design may limit generalizability. The 2×2 factorial design adds complexity to interpretation."},{"rthcId":"RPEP-11866","title":"Effects of GLP-1 Receptor Agonists in Alcohol Use Disorder.","authors":"Klausen, Mette Kruse; Knudsen, Gitte Moos; Vilsbøll, Tina; Fink-Jensen, Anders","year":2025,"journal":"Basic & clinical pharmacology & toxicology, 136(3), e70004","doi":"10.1111/bcpt.70004","pmid":"39891507","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11867","title":"Optimized suction patch design for enhanced transbuccal macromolecular drug delivery.","authors":"Klein Cerrejon, David; Krupke, Hanna; Gao, Daniel; Paunović, Nevena; Sachs, David; Leroux, Jean-Christophe","year":2025,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 380, 875-891","doi":"10.1016/j.jconrel.2025.02.014","pmid":"39938719","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11868","title":"RapTB: a lung-derived hemoglobin fragment with activity against Mycobacterium tuberculosis.","authors":"Klevesath, Leonard; Noschka, Reiner; Vomhof, Thomas; Mohnani, Jacky; Grieshober, Mark; Michaelis, Jens; Walther, Paul; Rodriguez, Armando; Preising, Nico; Read, Clarissa; Wiese, Sebastian; Ständker, Ludger; Thal, Dietmar R; Münch, Jan; Stenger, Steffen","year":2025,"journal":"Frontiers in microbiology, 16, 1669022","doi":"10.3389/fmicb.2025.1669022","pmid":"41209728","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11869","title":"In-depth analysis of metabolic hormones and inflammatory markers following Roux-en-Y gastric bypass in humans and rodents: similarities and differences.","authors":"Kloock, Simon; Scheller, Lukas; Hasinger, Julia; Balonov, Ilja; Kurlbaum, Max; Fassnacht, Martin; Koschker, Ann-Cathrin; Seyfried, Florian; Dischinger, Ulrich","year":2025,"journal":"Diabetes research and clinical practice, 229, 112923","doi":"10.1016/j.diabres.2025.112923","pmid":"41005747","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11870","title":"The Effects of the Natriuretic Peptide System on Alveolar Epithelium in Heart Failure.","authors":"Knany, Yara; Kinaneh, Safa; Khoury, Emad E; Zohar, Yaniv; Abassi, Zaid; Azzam, Zaher S","year":2025,"journal":"International journal of molecular sciences, 26(7)","doi":"10.3390/ijms26073374","pmid":"40244257","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"ANP and BNP significantly reduced alveolar fluid clearance (AFC) in isolated rat lungs. The AFC rate dropped from 0.49 ± 0.02 mL/h in control rats to 0.26 ± 0.013 mL/h with ANP treatment and 0.19 ± 0.005 mL/h with BNP treatment.\n\nThe mechanism involved downregulation of active sodium transport components in alveolar epithelial cells, including Na+,K+-ATPase and epithelial sodium channels (ENaC). The peptides enhanced ubiquitination and degradation of αENaC through increased levels of Nedd4-2. In compensated congestive heart failure (CHF), ANP further reduced AFC, but in decompensated CHF, ANP partially restored AFC, revealing a stage-dependent role for natriuretic peptides in lung fluid regulation.","whyItMatters":"Pulmonary edema — fluid in the lungs — is one of the most dangerous complications of heart failure and a leading cause of hospital admissions. Understanding how natriuretic peptides regulate lung fluid clearance could lead to better-targeted treatments that help the lungs clear fluid without causing harmful side effects, particularly in patients with severe decompensated heart failure.","specificNumbers":"","methodology":"Researchers used an isolated liquid-filled lung model in rats to directly measure alveolar fluid clearance rates. Congestive heart failure was induced using the aortocaval fistula model in Sprague-Dawley rats. The expression of natriuretic peptides, Na+,K+-ATPase, sodium channels, and the ubiquitin ligase Nedd4-2 was assessed in alveolar epithelial cells. AFC was measured in sham controls, ANP-treated, BNP-treated, compensated CHF, and decompensated CHF groups.","limitations":"This is an animal study using rats, and findings may not directly translate to human lung physiology. The aortocaval fistula model of heart failure does not perfectly replicate all forms of human CHF. The isolated lung model, while useful for measuring fluid clearance, removes the lungs from the context of whole-body circulation and hormonal regulation. Specific sample sizes per group are not reported in the abstract. Long-term effects of natriuretic peptide manipulation on lung function were not assessed."},{"rthcId":"RPEP-11871","title":"Approaching therapy of Alzheimer's disease via the antidiabetic drug liraglutide-a study with streptozotocin intracerebroventricularly treated Wistar rats.","authors":"Knezovic, Ana; Hosch, Michael; Hamann, Catharina Sophia; Popp, Sandy; Ortega, Gabriela; Osmanovic-Barilar, Jelena; Grünblatt, Edna; Monoranu, Camelia; Riederer, Peter; Salkovic-Petrisic, Melita; Schmitt-Böhrer, Angelika","year":2025,"journal":"Journal of neural transmission (Vienna, Austria : 1996), 132(10), 1587-1608","doi":"10.1007/s00702-025-02979-z","pmid":"40646278","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In rats with STZ-induced brain insulin resistance (a model of sporadic Alzheimer's):\n\n• STZ-icv rats showed impaired spatial learning (Morris water maze), fear-motivated memory deficits (passive avoidance), reduced hippocampal neurogenesis, and downregulated insulin/glucose metabolism genes\n• 4 weeks of liraglutide (0.3 mg/kg subcutaneous) did NOT reverse spatial learning deficits in the Morris water maze\n• Liraglutide WORSENED passive avoidance performance (fear-motivated memory)\n• Liraglutide partially restored dysregulated gene expression in hippocampus and prefrontal cortex related to insulin signaling and glucose metabolism\n• However, liraglutide additionally stimulated neuroinflammation — potentially counteracting its beneficial gene expression effects","whyItMatters":"With clinical trials of GLP-1 drugs for Alzheimer's underway, this preclinical study provides a cautionary counterpoint. The finding that liraglutide worsened one type of memory and stimulated neuroinflammation — even while partially correcting metabolic gene expression — suggests that the relationship between GLP-1 signaling and brain function is more complex than simple insulin sensitization. These results could inform clinical trial design and patient selection.","specificNumbers":"","methodology":"Male Wistar rats received intracerebroventricular streptozotocin (3 mg/kg) or vehicle to induce an insulin-resistant brain state. Two months later, subcutaneous liraglutide (0.3 mg/kg) or vehicle was given daily for 4 weeks. Cognitive testing included the Morris water maze (spatial learning) and passive avoidance test (fear-motivated memory). Adult neurogenesis was quantified by immunohistochemistry. Gene expression for insulin signaling, glucose uptake, and neuroinflammation pathways was measured by quantitative real-time PCR in hippocampus and prefrontal cortex.","limitations":"Single dose level tested (0.3 mg/kg) — the authors acknowledge that refined dosing might yield different results. Treatment started 2 months after disease induction, which represents established disease rather than prevention. The STZ-icv model, while well-accepted, may not fully replicate human sporadic Alzheimer's. Only male rats were used. The 4-week treatment duration may be insufficient for full therapeutic effect. The specific neuroinflammatory pathways activated were not fully characterized."},{"rthcId":"RPEP-11872","title":"Translational Pharmacokinetics of Icotrokinra, a Targeted Oral Peptide that Selectively Blocks Interleukin-23 Receptor and Inhibits Signaling.","authors":"Knight, Beverly; Tammara, Brinda; Modi, Nishit B; Dallas, Shannon; Mardirosian, Saro; Wang, Jianyao; Laenen, Aline; Leclercq, Laurent; DiLoreto, Karen; Adriaenssen, Lieve; Moss, Darren; Polidori, David; Chaudhuri, Siladitya Ray; Park, Seonghee; Sensenhauser, Carlo; Ndifor, Anthony; Sukumaran, Siddharth; Baguet, Tristan; Shi, Yifan; Patel, Shefali; Geist, Brian; Fourie, Anne; Patch, Raymond; Sun, Chengzao; Barros, Stephanie A; Somani, Sandeep; Monshouwer, Mario","year":2025,"journal":"Dermatology and therapy, 15(9), 2495-2520","doi":"10.1007/s13555-025-01454-7","pmid":"40629250","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11873","title":"End-stage renal diseases associated with SGLT2 inhibitors versus GLP-1 receptor agonists in metabolic dysfunction-associated steatotic liver disease.","authors":"Ko, Hwa Yeon; Hong, Bin; Bea, Sungho; Bae, Jae Hyun; Cho, Young Min; Chang, Yoosoo; Ryu, Seungho; Byrne, Christopher D; Shin, Ju-Young","year":2025,"journal":"Diabetes research and clinical practice, 229, 112921","doi":"10.1016/j.diabres.2025.112921","pmid":"40998218","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11874","title":"New onset diabetic retinopathy with glucagon-like peptide-1 receptor agonists: A case report.","authors":"Ko, Jennifer; Jahromi, Yaseman","year":2025,"journal":"Journal of the American Pharmacists Association : JAPhA, 65(5), 102475","doi":"10.1016/j.japh.2025.102475","pmid":"40609682","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11875","title":"Lipid nanoparticle encapsulated TLR3 agonist adjuvant elicits potent T cell immunity against cancer and viruses.","authors":"Ko, Kwang Hyun; Lee, Seung-Hwan; Choi, Young-Ho; Kang, Soon Myung; Yang, Hyun-Suk; Lee, So Min; Jo, Eun Bi; Bae, Hyun Shik; Hong, Seung-Beom; Kim, Dong-Ho; Cha, Seung Bin","year":2025,"journal":"NPJ vaccines, 11(1), 26","doi":"10.1038/s41541-025-01349-w","pmid":"41436456","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11876","title":"Automated pain assessment based on facial expression of free-moving mice.","authors":"Kobayashi, Koji; Sakamoto, Naoaki; Miyazaki, Yusuke; Yamamoto, Masahito; Murata, Takahisa","year":2025,"journal":"PNAS nexus, 4(11), pgaf352","doi":"10.1093/pnasnexus/pgaf352","pmid":"41245089","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11877","title":"Exploring the nephroprotective effects of combined finerenone and exenatide therapy in diabetic nephropathy.","authors":"Kocak, Ayse; Aydin, Elif; Gündüz, Meliha Koldemir; Kaymak, Güllü; Aydin, Bünyamin; Değer, Ayşe Nur","year":2025,"journal":"International immunopharmacology, 167, 115661","doi":"10.1016/j.intimp.2025.115661","pmid":"41101220","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11878","title":"Impact of Incretin-Based Therapy on Skeletal Muscle Health.","authors":"Koceva, Andrijana; Janež, Andrej; Jensterle, Mojca","year":2025,"journal":"Medicina (Kaunas, Lithuania), 61(9)","doi":"10.3390/medicina61091691","pmid":"41011082","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11879","title":"Preconception use of GLP-1 and GLP-1/GIP receptor agonists for obesity treatment.","authors":"Koceva, Andrijana; Janež, Andrej; Jensterle, Mojca","year":2025,"journal":"Best practice & research. Clinical endocrinology & metabolism, 39(6), 102038","doi":"10.1016/j.beem.2025.102038","pmid":"41015723","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11880","title":"Molecular mimicry: ecology, evolution, and applications of doppelgänger peptides.","authors":"Koch, Thomas L; Robinson, Samuel D; Safavi-Hemami, Helena","year":2025,"journal":"Trends in biochemical sciences, 50(9), 795-809","doi":"10.1016/j.tibs.2025.06.011","pmid":"40675901","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Doppelgänger peptides — molecular mimics of endogenous hormones or neuropeptides — have been discovered in many venomous organisms, poisonous species, parasites, and pathogens. While traditionally discovered anecdotally, the explosion of genomic sequence data combined with computational screening tools reveals they are far more prevalent than previously recognized.\n\nThese peptides evolved to manipulate the signaling systems of other organisms, making them inherently bioactive at relevant receptors. This positions them as candidates for translational applications in peptide-based therapeutics, building on the precedent set by venom-derived drugs like exenatide (from Gila monster) and ziconotide (from cone snails).","whyItMatters":"Some of the most successful peptide drugs in history were discovered by accident in venoms. This review argues we should be systematically searching for more. With modern genomics and AI-powered computational tools, the field can move from anecdotal discovery to systematic mining of nature's vast library of bioactive peptide mimics, potentially yielding an entire new class of therapeutics.","specificNumbers":"","methodology":"This is a comprehensive review published in Trends in Biochemical Sciences, synthesizing evidence across chemical ecology, molecular evolution, and drug development. The authors reviewed the literature on molecular mimicry in venomous, poisonous, and parasitic organisms, and assessed how emerging computational and sequencing technologies are accelerating discovery of new doppelgänger peptides.","limitations":"As a review article, no new experimental data were presented. The translational potential of most discovered doppelgänger peptides remains theoretical, with significant work needed to validate drug candidates. Computational predictions of molecular mimicry may generate false positives. The path from identified mimic to approved drug is long and expensive."},{"rthcId":"RPEP-11881","title":"A Once-Weekly C-Type Natriuretic Peptide for Treatment of Heart Failure with Preserved Ejection Fraction.","authors":"Kodal, Anne Louise Bank; Ewald, Jakob; Poulsen, Christian; Bonde, Mathilde Frederikke Bjørn; Kirchhoff, Jeppe Egedal; Poulsen, Svend; Schultz, Heidi Schiøler; Pedersen, Karen-Margrethe; Martis, Lena-Sophie; Kirk, Rikke K; Madsen, Kim Grimstrup; Sørensen, Simone Nymann; Alifrangis, Lene; Wilbs, Jonas; Madsen, Peter; Ludvigsen, Trine Pagh; Pedersen, Tanja Xenia; Fulle, Simone; Tornøe, Christian W; Nørager, Nina; Schjeltved, Rie Kristine; Ottosen, Mette Friis; Wulff-Larsen, Pernille Gry; Schmidt, Steffen; Røder, Gustav; Østergaard, Mette Viberg; Jumaa, Haidar; Dalsgaard, Charlotte Maria; Sonne, Kim; Rahbek-Nielsen, Henrik; Reinau, Marika Ejby; Burnage, Samual Charles; Leurs, Ulrike; Nielsen, Line Marie; Conde-Frieboes, Kilian W; Scully, Conor C G; Gruhler, Albrecht; Coppieters, Ken; Nyberg, Michael","year":2025,"journal":"Journal of medicinal chemistry, 68(24), 26365-26382","doi":"10.1021/acs.jmedchem.5c02467","pmid":"41378963","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11882","title":"Prognostic Value of Natriuretic Peptide Levels in Heart Failure With Recovered Ejection Fraction.","authors":"Kodur, Nandan; Gunsalus, Paul; Milinovich, Alex; Dalton, Jarrod E; Tang, W H Wilson","year":2025,"journal":"Circulation. Heart failure, 18(11), e013386","doi":"10.1161/CIRCHEARTFAILURE.125.013386","pmid":"41178541","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11883","title":"The Role of Bariatric Surgery in the Era of GLP-1 Receptor Agonists.","authors":"Koeller, Eva; Romanelli, John","year":2025,"journal":"Rhode Island medical journal (2013), 108(12), 24-28","doi":null,"pmid":"41284403","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11884","title":"\"Perioperative GLP-1 Receptor Agonist Use & Surgical Outcomes in Non-bariatric Abdominal Panniculectomy: A 10-Year Retrospective Analysis\".","authors":"Koenig, Zachary A; Rashid, Sydney; Hobbs, Gerlad R; Uygur, Halil Safak","year":2025,"journal":"Plastic and reconstructive surgery","doi":"10.1097/PRS.0000000000012405","pmid":"40875227","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11885","title":"Dual Targeting Approach Using 4-Hydroxytamoxifen Neuropeptide Y Conjugates for Selective Addressing of Adipose Tissue.","authors":"Kohler, Anna; Jülke, Eva-Maria; Darveniza, Luke C; Stichel, Jan; Beck-Sickinger, Annette G","year":2025,"journal":"ChemMedChem, 20(24), e202500668","doi":"10.1002/cmdc.202500668","pmid":"41151843","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11886","title":"Association between eating behavior patterns and the therapeutic efficacy of GLP-1 receptor agonists in individuals with type 2 diabetes: a multicenter prospective observational study.","authors":"Koide, Yuya; Kato, Takehiro; Hayashi, Makoto; Daido, Hisashi; Maruyama, Takako; Ishihara, Takuma; Nishimura, Kayoko; Tsunekawa, Shin; Yabe, Daisuke","year":2025,"journal":"Frontiers in clinical diabetes and healthcare, 6, 1638681","doi":"10.3389/fcdhc.2025.1638681","pmid":"41040428","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11887","title":"Predictors of patients with advanced pancreatic cancer undergoing conversion surgery via chemoimmunotherapy with a multifunctional Wilms' tumor 1 (WT1) peptide cocktail-pulsed dendritic cell vaccine.","authors":"Koido, Shigeo; Taguchi, Junichi; Shimabuku, Masamori; Bito, Tuuse; Morimoto, Soyoko; Oji, Yusuke; Oka, Yoshihiro; Ito, Masaki; Shimizu, Yoko; Ito, Zensho; Uchiyama, Kan; Saruta, Masayuki; Sato, Nobuhiro; Ohkusa, Toshifumi; Shimodaira, Shigetaka; Sugiyama, Haruo","year":2025,"journal":"Journal for immunotherapy of cancer, 13(7)","doi":"10.1136/jitc-2024-011426","pmid":"40744662","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11888","title":"An ACTH-Producing Neuroendocrine Tumor: Clinical Course of Multidisciplinary Therapy Including Peptide Receptor Radionuclide Therapy - A Case Report.","authors":"Koizumi, Tomonobu; Sato, Ai; Kitajima, Kohei; Yamazaki, Masanori; Kanazawa, Sana; Notake, Tsuyoshi; Sato, Yoshinori; Kobayashi, Shota; Iwaya, Mai; Umeda, Takako; Komatsu, Mitsuhisa","year":2025,"journal":"Case reports in oncology, 18(1), 181-189","doi":"10.1159/000543177","pmid":"39980506","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11889","title":"Emerging pharmacotherapies for obesity: A systematic review.","authors":"Kokkorakis, Michail; Chakhtoura, Marlene; Rhayem, Caline; Al Rifai, Jana; Ghezzawi, Malak; Valenzuela-Vallejo, Laura; Mantzoros, Christos S","year":2025,"journal":"Pharmacological reviews, 77(1), 100002","doi":"10.1124/pharmrev.123.001045","pmid":"39952695","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identified 53 phase 2/3 trials covering 36 emerging antiobesity drugs or combinations. Key findings:\n- Almost half of drugs in phase 2 trials are incretin analogs\n- Completed phase 2 incretin-based therapies achieved 7.4-24.2% mean weight loss\n- Oral semaglutide 50mg is the only drug to have completed a phase 3 trial\n- 14 ongoing phase 3 trials include: GLP-1 RAs (ecnoglutide, orforglipron, TG103), GLP-1/amylin (CagriSema), GLP-1/glucagon dual agonists (mazdutide, survodutide), GLP-1/GIP/glucagon triple agonist (retatrutide)\n- 4 trials were withdrawn or terminated\n\nThe review highlights that data on mortality, cardiovascular outcomes, long-term safety, cost-effectiveness, and underrepresented populations remain critical gaps.","whyItMatters":"This review provides the most comprehensive map of the obesity drug pipeline, confirming that peptide-based incretin therapies are the dominant and most promising class. Understanding which peptide drugs are in development, their mechanisms, and their weight loss potential is essential for clinicians, patients, and investors tracking the future of obesity treatment.","specificNumbers":"","methodology":"Systematic review of phase 2 and phase 3 trials in adults with overweight/obesity, searching Medline, Embase, and ClinicalTrials.gov from 2012 to 2024. Trials comparing novel weight loss pharmacotherapies to placebo/control or FDA-approved weight loss medication were included.","limitations":"The review covers trials through 2024 and may miss newer developments. Only phase 2 and 3 trials were included, so earlier-stage peptide drugs are not covered. Many included trials are ongoing with incomplete results. The review cannot compare drugs directly across different trials due to varying study designs, populations, and endpoints. Long-term data (>2 years) is limited for most emerging agents."},{"rthcId":"RPEP-11890","title":"Rebound or Retention: A Meta-Analysis of Weight Regain After the Discontinuation of Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists and Other Anti-obesity Drugs.","authors":"Kolli, Ravi Teja; Aoutla, Sridevi; Jyothi, Nirmal; Mohamed Kalifa, Mohamed Raghib Hussain; Raju, Arvin; Cheenikkal Muralidharan, Kavya","year":2025,"journal":"Cureus, 17(10), e94926","doi":"10.7759/cureus.94926","pmid":"41116804","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11891","title":"Dosimetry-guided peptide receptor radionuclide therapy in neuroendocrine tumors: interim safety analysis of the DUONEN trial.","authors":"Kolodziej, Maciej; Opalinska, Marta; Mikolajczak, Renata; Hubalewska-Dydejczyk, Alicja; Dedecjus, Marek; Kowalska, Aldona; Saracyn, Marek; Garnuszek, Piotr; Cieszykowska, Izabela; Januszkiewicz-Caulier, Joanna; Dlugosinska, Joanna; Durma, Adam Daniel; Jozwik-Plebanek, Katarzyna; Mroz, Adrianna; Janiak, Katarzyna; Gasior-Perczak, Danuta; Trofimiuk-Muldner, Malgorzata; Sowa-Staszczak, Anna; Braziewicz, Janusz; Lenda-Tracz, Wioletta; Kacperski, Krzysztof; Budzynska, Anna; Kubik, Agata; Pastusiak, Patrycja; Chalewska, Wioletta; Borkowska, Anna; Cegla, Paulina; Walecka-Mazur, Agata; Szczodry, Artur; Kaminski, Grzegorz","year":2025,"journal":"Frontiers in endocrinology, 16, 1716247","doi":"10.3389/fendo.2025.1716247","pmid":"41404513","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11892","title":"Sensory neurons shape local macrophage identity via TGF-β signaling.","authors":"Kolter, Julia; Döring, Clarissa-Laura; Sarout, Samah; Baasch, Sebastian; Steele, Lloyd; Alsumati, Reem; Lucena Silva, Gabriel V; Aníbal Silva, Conceição E; Paiva, Isadora Marques; Mansoori Moghadam, Zohreh; Gres, Vitka; Lohrmann, Florens; Aktories, Philipp; Buchegger, Theresa; Bijnen, Mitchell; Doumard, Layal; Voisin, Benjamin; Le Foll, Christelle; Lachmann, Nico; Greter, Melanie; Kierdorf, Katrin; Haniffa, Muzlifah; Cunha, Thiago M; Flacher, Vincent; Henneke, Philipp","year":2025,"journal":"Immunity, 58(10), 2556-2573.e8","doi":"10.1016/j.immuni.2025.08.004","pmid":"40914152","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11893","title":"Determinants and Clinical Impact of Visit-to-visit Blood Pressure Variability in Patients with Heart Failure with Preserved Ejection Fraction.","authors":"Komiyama, Chinatsu; Kagiyama, Nobuyuki; Yuri, Takuya; Hayashida, Akihiro; Hirohata, Atsushi; Yoshida, Kiyoshi; Matsue, Yuya; Minamino, Tohru","year":2025,"journal":"JMA journal, 8(3), 871-881","doi":"10.31662/jmaj.2024-0256","pmid":"40786446","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11894","title":"Efficacy and Safety of Tirzepatide on Weight Loss in Patients Without Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.","authors":"Kommu, Sharath; Sharma, Param P; Gabor, Rachel M","year":2025,"journal":"Obesity reviews : an official journal of the International Association for the Study of Obesity, 26(11), e13961","doi":"10.1111/obr.13961","pmid":"40510020","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11895","title":"Time-course analysis of the effect of paraprobiotics ABG0050 on the intestinal immune system of broilers.","authors":"Kondo, Hiroya; Iino, Shiori; Fukuda, Takako; Aoki, Mikio; Yoshimura, Yukinori; Isobe, Naoki; Nii, Takahiro","year":2025,"journal":"Poultry science, 104(7), 105174","doi":"10.1016/j.psj.2025.105174","pmid":"40267562","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11896","title":"Comparison of Exendin-4 and Its Single Amino Acid Substitutions as Parent Peptides for GLP-1 Receptor Imaging Probes.","authors":"Kondo, Naoya; Yonezawa, Maiko; Hirano, Fuko; Temma, Takashi","year":2025,"journal":"Molecules (Basel, Switzerland), 30(5)","doi":"10.3390/molecules30051011","pmid":"40076236","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The Ex-D3 variant (Glu3Asp substitution of exendin-4) showed several advantages over standard exendin-4 as a GLP-1R imaging probe:\n\n- C-terminal modification for iodine-125 labeling did not significantly alter GLP-1R binding affinity (confirmed by surface plasmon resonance)\n- Ex-D3-C40 induced weaker hypoglycemic effects than Ex-4-C40 in mice, reducing the safety risk\n- Iodine-125 labeled Ex-D3 achieved significantly higher pancreatic accumulation than labeled Ex-4\n- Higher pancreas-to-blood and pancreas-to-muscle ratios, indicating better imaging contrast\n- Ex vivo autoradiography confirmed specific binding to GLP-1R-expressing pancreatic β-cells\n- The higher internalization rate of Ex-D3 likely contributes to improved tissue accumulation","whyItMatters":"Imaging GLP-1 receptors is clinically important for diagnosing insulinomas, monitoring beta cell mass in diabetes, and evaluating transplanted islet cells. Current exendin-4-based probes carry a risk of dangerous hypoglycemia that limits their use. A probe that images better while being safer could expand clinical applications of GLP-1R imaging and benefit patients who most need it.","specificNumbers":"","methodology":"Researchers synthesized exendin-4 and Ex-D3 derivatives with C-terminal cysteine additions for site-specific iodine-125 labeling. Binding affinity was assessed using surface plasmon resonance. In vivo studies in mice measured blood glucose effects and biodistribution of the radiolabeled peptides. Ex vivo autoradiography confirmed binding specificity to GLP-1R-expressing pancreatic beta cells.","limitations":"This is a preclinical mouse study with no human data. The comparison was limited to iodine-125 labeling; other radioisotopes commonly used in clinical imaging (gallium-68, fluorine-18) were not tested. Long-term toxicity and immunogenicity were not assessed. The study does not quantify the degree of hypoglycemia reduction in absolute terms. Translation to human imaging would require further development and clinical validation."},{"rthcId":"RPEP-11897","title":"Effects of Sacubitril/Valsartan According to Natriuretic Peptide Levels in Patients Enrolled in PARADIGM-HF and PARAGON-HF.","authors":"Kondo, Toru; Jhund, Pardeep S; Anand, Inder S; Claggett, Brian L; Desai, Akshay S; Docherty, Kieran F; Lam, Carolyn S P; Lefkowitz, Martin P; Maggioni, Aldo P; Martinez, Felipe A; Redfield, Margaret M; Rouleau, Jean L; Van Veldhuisen, Dirk J; Zannad, Faiez; Zile, Michael R; Packer, Milton; Solomon, Scott D; McMurray, John J V","year":2025,"journal":"JACC. Heart failure, 13(6), 927-939","doi":"10.1016/j.jchf.2024.12.010","pmid":"40088233","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11898","title":"Christensenella intestinihominis MNO-863 improve obesity and related metabolic disorders via SCFAs-induced GLP-1 hormone secretion.","authors":"Kong, Ping; Xian, Yibo; Lao, Canshan; Huang, Baojia; Zhang, Dongya; Tai, Lihong; Zhao, Yingying; Pu, Zilun; Lan, Zhou; Zhang, Chenchen; Liu, Zhenzhen; Xiao, Chen; Zhao, Guozhen; Zhu, Ruijuan; Liang, Yajun; Lin, Chuan-Sheng; Lin, Jing-Han; Sun, Jing-Zu; Wang, Tao; Liu, Hong-Wei; Jiang, Xianzhi","year":2025,"journal":"Frontiers in nutrition, 12, 1668786","doi":"10.3389/fnut.2025.1668786","pmid":"41356823","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11899","title":"Pharmacological treatment options for metabolic dysfunction-associated steatotic liver disease in patients with type 2 diabetes mellitus: A systematic review.","authors":"Konings, Laura A M; Miguelañez-Matute, Lorena; Boeren, Anna M P; van de Luitgaarden, Inge A T; Dirksmeier, Femme; de Knegt, Rob J; Tushuizen, Maarten E; Grobbee, Diederick E; Holleboom, Adriaan G; Cabezas, Manuel Castro","year":2025,"journal":"European journal of clinical investigation, 55(4), e70003","doi":"10.1111/eci.70003","pmid":"39937036","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11900","title":"Enhancing glioblastoma therapy via intranasal administration of highly potent cell-penetrating peptide decorated nanoparticles.","authors":"Koo, Jain; Shin, Yuseon; Jeon, Hyewon; Cheong, Jaehyun; Cho, Seongmin; Park, Chanho; Song, Ee Chan; Ramsey, Jacob D; Lim, Chaemin; Oh, Kyung Taek","year":2025,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 378, 997-1012","doi":"10.1016/j.jconrel.2024.12.058","pmid":"39724950","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11901","title":"A conceptual framework for the intersection of hyperalgesia and hyperkatifeia in alcohol addiction.","authors":"Koob, George F; Vendruscolo, Leandro F","year":2025,"journal":"Alcohol (Fayetteville, N.Y.), 129, 1-13","doi":"10.1016/j.alcohol.2025.08.004","pmid":"40876667","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11902","title":"Intratracheal Delivery of a Phospholamban Decoy Peptide Attenuates Cardiac Damage Following Myocardial Infarction.","authors":"Kook, Taewon; Lee, Mi-Young; Kwak, Tae Hwan; Jeong, Dongtak; Sim, Doo Sun; Jeong, Myung Ho; Ahn, Youngkeun; Kook, Hyun; Park, Woo Jin; Jang, Seung Pil","year":2025,"journal":"International journal of molecular sciences, 26(6)","doi":"10.3390/ijms26062649","pmid":"40141290","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11903","title":"Network meta-analysis comparing efficacy of different strategies on medication-overuse headache.","authors":"Koonalintip, Prut; Yamutai, Suppakorn; Setthawatcharawanich, Suwanna; Thongseiratch, Therdpong; Chichareon, Ply; Wakerley, Benjamin R","year":2025,"journal":"The journal of headache and pain, 26(1), 43","doi":"10.1186/s10194-025-01982-9","pmid":"40011869","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11904","title":"The role of agomelatine in appetite regulation and body weight in rats.","authors":"Korkmaz, Engin; Erden, Yavuz; Tekin, Çiğdem; Tekin, Suat","year":2025,"journal":"Experimental physiology","doi":"10.1113/EP092783","pmid":"40801490","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11905","title":"Vasoactive Intestinal Peptide (VIP) and its Receptors in Adipose Tissue: Implications for Cold Stress Adaptation.","authors":"Korkmaz, Orhan Tansel; Saydam, Faruk; Dalkiran, Bahar; Değirmenci, İrfan; Tunçel, Neşe","year":2025,"journal":"Cell biochemistry and biophysics, 83(2), 1963-1972","doi":"10.1007/s12013-024-01606-0","pmid":"39550744","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11906","title":"Efficacy and Safety of GLP-1 RAs in Children and Adolescents With Obesity or Type 2 Diabetes: A Systematic Review and Meta-Analysis.","authors":"Kotecha, Pareeta; Huang, Wenxi; Yeh, Ya-Yun; Narvaez, Valerie Martino; Adirika, Darlene; Tang, Huilin; Bernier, Angelina V; Westen, Sarah C; Smith, Steven M; Bian, Jiang; Guo, Jingchuan","year":2025,"journal":"JAMA pediatrics, 179(12), 1308-1317","doi":"10.1001/jamapediatrics.2025.3243","pmid":"40952752","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 18 RCTs (1,402 participants; mean age 13.7 years; 59.3% female; median treatment 0.51 years), GLP-1 RAs vs. placebo showed:\n\n- HbA1c: -0.44% (95% CI: -0.68% to -0.21%)\n- Fasting glucose: -9.92 mg/dL (95% CI: -16.20 to -3.64)\n- Body weight: -3.02 kg (95% CI: -4.98 to -1.06)\n- BMI: -1.45 (95% CI: -2.40 to -0.49)\n- BMI SDS: -0.20 (95% CI: -0.36 to -0.05)\n- BMI percentile: -7.24% (95% CI: -12.97% to -1.51%)\n- Systolic blood pressure: -2.73 mmHg (95% CI: -4.04 to -1.43)\n- GI adverse events: increased (log RR 0.75)\n- Suicidal ideation/behaviors: no significant difference vs. placebo\n\nAll efficacy outcomes reached statistical significance, supporting GLP-1 RAs for pediatric use.","whyItMatters":"As pediatric obesity reaches epidemic proportions, safe and effective pharmacotherapy options are desperately needed. This comprehensive meta-analysis from JAMA Pediatrics provides the strongest evidence to date that GLP-1 drugs work in young people, with a favorable safety profile regarding the critical concern of mental health side effects.","specificNumbers":"","methodology":"Systematic review and meta-analysis following PRISMA guidelines. Searched PubMed, Embase, and Cochrane CENTRAL from inception through February 2025. Included 18 RCTs comparing GLP-1 RAs to placebo in children and adolescents under 18 with obesity, overweight, prediabetes, or T2D. Two independent reviewers extracted data and assessed risk of bias using Cochrane RoB2. Random-effects inverse variance models were used for all analyses.","limitations":"The median treatment duration was only about 6 months — long-term safety and efficacy in growing children remain unknown. The total sample size (1,402) is relatively modest for a meta-analysis. Effects on growth, puberty, bone health, and long-term mental health development were not assessed. Most trials studied a limited age range (mean 13.7 years), with less data for younger children."},{"rthcId":"RPEP-11907","title":"Risk of Suicidal Ideation and Behaviors, Depression, and Anxiety with GLP-1 Receptor Agonist Use in Children and Adolescents: A Target Trial Emulation Study.","authors":"Kotecha, Pareeta; Lee, Yao An; Bernier, Angelina V; Westen, Sarah C; Smith, Steven M; Zhang, Pengyue; Hannon, Tamara S; Bian, Jiang; Guo, Jingchuan","year":2025,"journal":"medRxiv : the preprint server for health sciences","doi":"10.1101/2025.11.11.25339931","pmid":"41292652","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among approximately 2,000 children and adolescents (mean age ~14.2 years, ~61% female) with up to 4 years of follow-up:\n\n- Suicidal ideation/behaviors: GLP-1 RA users had significantly lower risk (HR 0.11, 95% CI 0.02-0.86; risk difference -10.45 per 1,000 person-years)\n- Depression: GLP-1 RA users had significantly lower risk (HR 0.37, 95% CI 0.17-0.78; risk difference -25.64 per 1,000 person-years)\n- Anxiety: No significant difference (HR 1.13, 95% CI 0.69-1.84; risk difference 5.95 per 1,000 person-years)\n\nAll comparisons were against prevalent metformin users.","whyItMatters":"With GLP-1 drugs increasingly prescribed to children and teens for obesity, the European Medicines Agency and FDA have flagged concerns about potential suicide risk. This study provides the first large pediatric-specific evidence and finds the opposite — these drugs may actually be protective for mental health. This is critical information for parents, pediatricians, and regulators making prescribing decisions.","specificNumbers":"","methodology":"Retrospective cohort study using the OneFlorida+ electronic health records database (January 2020 to January 2024). The study used a prevalent-new user design with target trial emulation framework and stabilized inverse probability of treatment weighting (sIPTW) for confounding control. Weighted Cox proportional hazards models assessed the risk of suicidal ideation/behaviors, depression, and anxiety in children and adolescents (age 6-17) starting GLP-1 RAs compared to prevalent metformin users.","limitations":"This is a retrospective observational study (preprint, not yet peer-reviewed), so it cannot establish causation. The comparison with metformin users may introduce selection bias. The confidence interval for suicidal ideation/behaviors was wide (HR 0.02-0.86), reflecting small event numbers. The anxiety finding showed a non-significant upward trend that warrants monitoring. Confounding by indication (more depressed patients might not be prescribed GLP-1 RAs) cannot be fully excluded despite weighting."},{"rthcId":"RPEP-11908","title":"Basal insulin in the age of innovation: are diamonds still forever?","authors":"Koufakis, Theocharis; Patoulias, Dimitrios; Popovic, Djordje S; Tsimihodimos, Vasileios","year":2025,"journal":"Expert review of endocrinology & metabolism, 20(6), 471-474","doi":"10.1080/17446651.2025.2580629","pmid":"41139150","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 receptor agonists and dual incretin agonists (like tirzepatide) are increasingly prioritized over basal insulin for type 2 diabetes due to superior efficacy, cardiovascular benefits, weight loss, and safety. However, basal insulin remains indispensable for patients with advanced beta-cell failure, severe hyperglycemia, or contraindications to newer agents. The review advocates personalized, pathophysiology-driven therapy selection including integration of new once-weekly insulin formulations.","whyItMatters":"The diabetes treatment hierarchy is rapidly being rewritten by peptide-based incretin drugs. This review captures a pivotal moment: GLP-1 agonists and dual incretins are displacing insulin from its decades-long position as the default treatment intensification option, fundamentally changing how type 2 diabetes is managed.","specificNumbers":"GLP-1 RAs, SGLT2 inhibitors, dual incretin agonists vs basal insulin · once-weekly insulin formulations · personalized therapy selection","methodology":"Expert review article with targeted PubMed literature search focusing on cardiovascular outcomes trials, head-to-head comparison studies, and major diabetes treatment guidelines comparing newer agents (GLP-1 RAs, SGLT2i, dual incretins) to basal insulin.","limitations":"Expert opinion/editorial format rather than systematic review. Brief article (4 pages). Does not quantify specific outcome differences between drug classes. May not capture the full breadth of patient scenarios. Does not address cost-effectiveness or global access disparities."},{"rthcId":"RPEP-11909","title":"Circulating Beta-Defensin 2 Levels Correlate with Conventional Inflammatory Markers in Infection-Free Individuals with Overweight and Obesity: An Exploratory Study.","authors":"Koufakis, Theocharis; Kouroupis, Dimitrios; Dimakopoulos, Georgios; Georgiadis, Theofylaktos; Kourti, Areti; Karalazou, Paraskevi; Thisiadou, Katerina; Doukelis, Panagiotis; Zografou, Ioanna; Patoulias, Dimitrios; Popovic, Djordje S; Pyrpasopoulou, Athina; Fousteris, Evangelos; Argyrakopoulou, Georgia; Kokkinos, Alexander; Giouleme, Olga; Kotsa, Kalliopi; Doumas, Michael; Makedou, Kali","year":2025,"journal":"Biomedicines, 13(8)","doi":"10.3390/biomedicines13081800","pmid":"40868054","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11910","title":"Preliminary Study on Circulating REG3α and Its Associations with Vitamin D Supplementation and Inflammatory Biomarkers in Adults with Overweight and Obesity.","authors":"Koufakis, Theocharis; Kouroupis, Dimitrios; Kourti, Areti; Karalazou, Paraskevi; Thisiadou, Katerina; Georgiadis, Ioannis; Mustafa, Omar; Maltese, Giuseppe; Busetto, Luca; Popovic, Djordje S; Giouleme, Olga; Kotsa, Kalliopi; Doumas, Michael; Makedou, Kali","year":2025,"journal":"Current issues in molecular biology, 47(12)","doi":"10.3390/cimb47120970","pmid":"41614735","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11911","title":"The Impact of Glucagon-like Peptide-1 Receptor Agonists on Erectile Function: Friend or Foe?","authors":"Kounatidis, Dimitris; Vallianou, Natalia G; Rebelos, Eleni; Vallianou, Kalliopi; Diakoumopoulou, Evanthia; Makrilakis, Konstantinos; Tentolouris, Nikolaos","year":2025,"journal":"Biomolecules, 15(9)","doi":"10.3390/biom15091284","pmid":"41008590","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11912","title":"Minimal Change Podocytopathy with Coexistent Thin Glomerular Basement Membrane following Exposure to Semaglutide.","authors":"Kovvuru, Karthik; Kanduri, Swetha Rani; Phillips, Johnathon; Velez, Juan Carlos","year":2025,"journal":"Glomerular diseases, 5(1), 103-108","doi":"10.1159/000543357","pmid":"40035048","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11913","title":"The effects of corticotropin-releasing factor (CRF) and urocortins on the serotonin (hydroxytryptamine, 5HT) released from the raphe nuclei (RN).","authors":"Kovács, Aliz; Tancsics, Patrícia; Palotai, Miklós; Bagosi, Zsolt","year":2025,"journal":"Neuropeptides, 110, 102503","doi":"10.1016/j.npep.2025.102503","pmid":"39798539","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11914","title":"Upstream open reading frame translation enhances immunogenic peptide presentation in mitotically arrested cancer cells.","authors":"Kowar, Alexander; Becker, Jonas P; Del Pizzo, Rossella; Tang, Zhiwei; Champagne, Julien; Wellach, Kathrin; Samimi, Kiana; Galindo-Albarrán, Ariel; Körner, Pierre-René; Montenegro Navarro, Jasmine; Elía, Andrés; Tilghman, Fiona Megan; Sakeer, Hanan; Mendoza-Parra, Marco Antonio; Riemer, Angelika B; Agami, Reuven; Loayza-Puch, Fabricio","year":2025,"journal":"Nature communications, 16(1), 8008","doi":"10.1038/s41467-025-63405-2","pmid":"40866359","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Mitotic cancer cells redistribute their ribosomes toward the 5' untranslated region and the beginning of the coding sequence, leading to enhanced translation of thousands of upstream open reading frames (uORFs) and upstream overlapping open reading frames (uoORFs). These non-canonical translation products are presented on the cancer cell surface via HLA molecules after treatment with mitotic inhibitors.\n\nFunctional assays confirmed that these newly presented peptide epitopes provoke T cell-mediated killing of cancer cells, demonstrating that mitotic arrest creates a window of immune vulnerability for tumors.","whyItMatters":"Drug resistance is a major challenge in cancer treatment with mitotic inhibitors. This discovery reveals that even when these drugs don't directly kill all cancer cells, they may make tumors more visible to the immune system by forcing cells to display unusual peptides. This opens up combination strategies pairing mitotic inhibitors with immunotherapy.","specificNumbers":"","methodology":"The researchers studied ribosome redistribution in mitotically arrested cancer cell lines, mapping translation changes across the 5' UTR and coding regions. They analyzed HLA-presented peptides on cell surfaces after mitotic inhibitor treatment, identifying non-canonical peptides derived from uORFs and uoORFs. They then performed functional T cell killing assays to confirm these epitopes could trigger an immune response.","limitations":"The findings are from cancer cell line experiments and functional assays in vitro, not from animal models or clinical trials. The study does not quantify what proportion of mitotically arrested cells present sufficient epitopes for immune clearance. Whether this mechanism operates effectively in the immunosuppressive tumor microenvironment in vivo remains to be determined."},{"rthcId":"RPEP-11915","title":"Design of Experiments Approach for the Development of a Validated UPLC-Q-ToF/MS Method to Quantitate Soy-Derived Bioactive Peptide Lunasin in Rabbit Plasma: Application to a Pharmacokinetic Study.","authors":"Kowmudi, Gullapalli; Anoop, Karthika; Varshini, Magham Sai; Nagappan, Krishnaveni; Konanki, Sreenath; Praveen, Thaggikuppe Krishnamurthy","year":2025,"journal":"Biomedical chromatography : BMC, 39(6), e70098","doi":"10.1002/bmc.70098","pmid":"40317539","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A validated UPLC-Q-ToF/MS method was developed with an LLOQ of 34.6 ng/mL and linearity from 35–10,000 ng/mL. Accuracy ranged from 86.7% to 88.9% recovery, with intraday precision <2.65% RSD and interday precision <6.22% RSD. The method was successfully applied to a pharmacokinetic study in rabbits given oral lunasin-rich processed soybeans at two doses (6.56 and 19.1 g/kg), confirming oral bioavailability of lunasin.","whyItMatters":"Lunasin has been studied for potential anti-cancer, anti-inflammatory, and cholesterol-lowering effects, but its clinical potential depends on whether it survives digestion and reaches the bloodstream. This study provides both the measurement tools and preliminary evidence that oral lunasin is bioavailable — a critical step toward understanding its therapeutic potential.","specificNumbers":"","methodology":"The analytical method was developed using design of experiments (DoE) methodology to optimize UPLC-Q-ToF/MS conditions. Separation used a BEH-C18 column with a 9-minute gradient. Neuropeptide Y served as the internal standard. The method was validated for accuracy, precision, linearity, and sensitivity, then applied to a pharmacokinetic study with oral lunasin administration to rabbits.","limitations":"The pharmacokinetic study was conducted in rabbits, and absorption patterns may differ in humans. Only processed soybean-derived lunasin was tested, not purified peptide. The abstract does not report specific PK parameters (Cmax, Tmax, AUC, half-life), limiting interpretation of the absorption profile. The sample size for the PK study was not specified."},{"rthcId":"RPEP-11916","title":"Neuropeptide Y drives ventricular arrhythmogenesis in chronic ischemic heart failure via calcium mishandling.","authors":"Koya, Jiro; Temma, Taro; Kawakami, Kei; Karube, Fuyuki; Tanei, Zen-Ichi; Kawasaki, Masahiro; Shimano, Kintaro; Saito, Shota; Tatsuta, Daishiro; Nishino, Kotaro; Natsui, Hiroyuki; Kadosaka, Takahide; Koya, Taro; Nakao, Motoki; Watanabe, Masaya; Kamiya, Kiwamu; Nagai, Toshiyuki; Tanaka, Shinya; Fujiyama, Fumino; Anzai, Toshihisa","year":2025,"journal":"Heart rhythm, 22(12), e1179-e1192","doi":"10.1016/j.hrthm.2025.08.011","pmid":"40803609","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11917","title":"Enduring Autism-like Phenotypes and Deregulated Hypothalamic Prosocial Peptides After Early-Life Exposure to Indoor Flame Retardants in Male C57BL/6 Mice.","authors":"Kozlova, Elena V; Gonzalez, Gwendolyn M; Denys, Maximillian E; Bishay, Anthony E; Gutierrez, Roberto; Reid, Jack; Krum, Julia M; Lampel, Gregory; Luvsanravdan, Naran; Rabbani, Kayhon M; Tu, Jordan; Campoy, Luis; Anchondo, Laura M; Luna, Crystal N; Olomi, Duraan S; Monarrez, Eduardo; Carrillo, Valeria; Tran, Jasmin D; Platt, Damon; Korde, Yash; Chinthirla, Bhuvaneswari D; Blaibel, Maher; Kim, Simon; Chompre, Gladys; Phillips, Allison L; Stapleton, Heather M; Henkelmann, Bernhard; Schramm, Karl-Werner; Curras-Collazo, Margarita C","year":2025,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2025.09.02.673882","pmid":"40950196","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11918","title":"Therapeutic effects of finerenone and exenatide on diabetes-induced heart failure: A combined approach targeting inflammation and oxidative stress.","authors":"Koçak, Ayşe; Günek, Emirhan; Aydın, Elif; Gündüz, Meliha Koldemir; Kaymak, Güllü","year":2025,"journal":"European journal of pharmacology, 1002, 177826","doi":"10.1016/j.ejphar.2025.177826","pmid":"40494432","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11919","title":"Oral semaglutide for the treatment of obesity: a retrospective real-world study.","authors":"Krajnc, Mitja; Kuhar, Neža; Koceva, Andrijana","year":2025,"journal":"Frontiers in endocrinology, 16, 1593334","doi":"10.3389/fendo.2025.1593334","pmid":"40510489","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11920","title":"Tirzepatide Reduces LV Mass and Paracardiac Adipose Tissue in Obesity-Related Heart Failure: SUMMIT CMR Substudy.","authors":"Kramer, Christopher M; Borlaug, Barry A; Zile, Michael R; Ruff, Dustin; DiMaria, Joseph M; Menon, Venu; Ou, Yang; Zarante, Angela M; Hurt, Karla C; Murakami, Masahiro; Packer, Milton","year":2025,"journal":"Journal of the American College of Cardiology, 85(7), 699-706","doi":"10.1016/j.jacc.2024.11.001","pmid":"39566869","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 106 patients with obesity-related heart failure with preserved ejection fraction (HFpEF), tirzepatide reduced left ventricular (LV) mass by 11 g (95% CI: -19 to -4 g, P = 0.004) and paracardiac adipose tissue by 45 mL (95% CI: -69 to -22 mL, P < 0.001) compared to placebo over 52 weeks.\n\nThe reduction in LV mass correlated with weight loss (P < 0.02) and tended to correlate with waist circumference and blood pressure changes (P = 0.06 for both). LV mass changes also correlated with reductions in LV end-diastolic volume and left atrial volumes (P < 0.03 for all), indicating broader cardiac remodeling benefits.","whyItMatters":"Obesity-related heart failure is a growing health crisis, and excess fat around the heart worsens cardiac function. This study provides imaging evidence that tirzepatide doesn't just help with weight loss — it directly reduces harmful structural changes in the heart. These findings help explain why tirzepatide reduced heart failure events in the main SUMMIT trial.","specificNumbers":"","methodology":"This was a substudy of the SUMMIT randomized controlled trial. 175 patients with obesity-related HFpEF underwent cardiac MRI at baseline, with 106 completing scans at both baseline and 52 weeks. Patients received tirzepatide (starting at 2.5 mg weekly, increasing to a maximum of 15 mg weekly via subcutaneous injection) or placebo. Researchers measured heart muscle mass, chamber volumes, and fat around the heart using multi-angle MRI sequences.","limitations":"The substudy included only 106 of the 731 patients from the parent trial, limiting statistical power. The study was not powered to detect changes in clinical outcomes like hospitalizations or death. Image quality issues excluded some participants. The 52-week follow-up may not capture long-term effects, and the correlation between weight loss and cardiac changes makes it difficult to determine whether tirzepatide has direct cardiac effects independent of weight loss."},{"rthcId":"RPEP-11921","title":"Cardioprotective effects of semaglutide on isolated human ventricular myocardium.","authors":"Krammer, Thomas; Baier, Maria J; Hegner, Philipp; Zschiedrich, Tilman; Lukas, David; Wolf, Matthias; Le Phu, Christian; Lutz, Vanessa; Evert, Katja; Kozakov, Kostiantyn; Li, Jing; Holzamer, Andreas; Maier, Lars S; Provaznik, Zdenek; Bers, Donald M; Wagner, Stefan; Mustroph, Julian","year":2025,"journal":"European journal of heart failure, 27(7), 1315-1325","doi":"10.1002/ejhf.3644","pmid":"40107718","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide demonstrated direct cardioprotective effects on isolated human cardiomyocytes from three groups: non-failing hearts, aortic stenosis with HFpEF-like phenotype, and end-stage HFrEF.\n\nKey findings included: reduction of late sodium current (INa) in diseased cardiomyocytes to levels comparable with non-failing hearts; decreased diastolic sarcoplasmic reticulum (SR) calcium leak; improved systolic calcium transients and contractility in both AS and HFrEF tissue; and dose-dependent improvement of myocardial contractility in multicellular preparations. These effects were mediated through GLP-1 receptor agonism (blocked by exendin 9-39) and were comparable to CaMKII inhibition.","whyItMatters":"Clinical trials have shown semaglutide reduces cardiovascular events, but no one knew exactly why at the cellular level. This study provides the first direct evidence that semaglutide acts on human heart cells themselves — not just indirectly through weight loss or blood sugar control — fixing the specific ion-handling defects that drive heart failure progression.","specificNumbers":"","methodology":"Human left ventricular cardiomyocytes were isolated from non-failing donor hearts, patients with aortic stenosis (HFpEF-like), and end-stage HFrEF patients. Researchers measured late sodium current, SR calcium leak, calcium transients, and contractility with and without semaglutide treatment. CaMKII inhibitor peptide and GLP-1 receptor antagonist were used to confirm the signaling pathway.","limitations":"This was an ex vivo study on isolated heart cells and tissue strips, which may not fully replicate the complexity of semaglutide's effects in a living patient. The concentration of semaglutide used in the lab may differ from what reaches the heart during clinical dosing. Sample sizes for each patient group were not specified in the abstract. Long-term effects on cardiac remodeling cannot be assessed in this experimental setting."},{"rthcId":"RPEP-11922","title":"An antibiotic-free antimicrobial combination of bacteriocins and a peptidoglycan hydrolase: in vitro and in vivo assessment of its efficacy.","authors":"Kranjec, Christian; Oftedal, Thomas F; Ovchinnikov, Kirill V; da Silva Duarte, Vinícius; Hermansen, Simen; Kaus-Drobek, Magdalena; Sabała, Izabela; Porcellato, Davide; Carlsen, Harald; Kjos, Morten","year":2025,"journal":"Applied and environmental microbiology, 91(7), e0243324","doi":"10.1128/aem.02433-24","pmid":"40552825","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11923","title":"The effect of glucagon-like peptide-1 agonists on ocular parameters in idiopathic intracranial hypertension patients: a retrospective study.","authors":"Kravetz, Liron; Leeman, Samuel; Regev, Tamir; Walter, Eyal; Horev, Anat; Ofri, Mai; Kerman, Tomer; Watted, Muhamad; Buklan, Karina; Hin, Wasim; Elobra, Yasmin; Tsumi, Erez","year":2025,"journal":"Eye (London, England), 39(10), 2090-2095","doi":"10.1038/s41433-025-03807-0","pmid":"40301667","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11924","title":"Switch from premixed insulin analogue to degludec-liraglutide combination: a CGM study.","authors":"Kravos Tramšek, Nika Aleksandra; Koceva, Andrijana; Krajnc, Mitja","year":2025,"journal":"Frontiers in endocrinology, 16, 1715800","doi":"10.3389/fendo.2025.1715800","pmid":"41268167","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11925","title":"Coincidence of Autoimmune Diabetes Mellitus and Familial Partial Lipodystrophy.","authors":"Krienke, Michelle; Schmidt, Hartmut H J; Buettner, Janine; Tan, Susanne; Schumann, Isabell; Miehle, Konstanze","year":2025,"journal":"JCEM case reports, 3(12), luaf265","doi":"10.1210/jcemcr/luaf265","pmid":"41221014","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11926","title":"Nanoparticle-mediated delivery of antimicrobial peptides for multidrug-resistant ventilator-associated pneumonia: a comprehensive review of a promising therapeutic strategy.","authors":"Krishnan, S Santhana; Jayanthi, N Nalini; Vajravelu, Leela Kagithakara; Santhiya, D","year":2025,"journal":"Archives of microbiology, 207(12), 316","doi":"10.1007/s00203-025-04497-8","pmid":"41108394","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11927","title":"Physician Perceptions of the Safety and Efficacy of GLP-1 Receptor Agonists: Underestimation of Cardiovascular Risk Reduction and Discrepancies with Clinical Evidence.","authors":"Krishnan, Srikanth; Srivastava, Pratyaksh K; Attaluri, Jayram; Nayeri, Rebecca; Chatterjee, Dhananjay; Patel, Jay; Nsair, Ali; Budoff, Matthew; Nayeri, Arash","year":2025,"journal":"Journal of cardiovascular development and disease, 12(1)","doi":"10.3390/jcdd12010019","pmid":"39852297","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11928","title":"The Effect of Oral Semaglutide on Cardiovascular Risk Factors in Patients with Type 2 Diabetes: A Systematic Review.","authors":"Krishnanda, Stanislaus Ivanovich; Christabelle, Marie; Yausep, Oliver Emmanuel; Sugiharto, Caroline; Vincent, Leroy David; Agarwal, Raksheeth; Damara, Ivan; Harbuwono, Dante Saksono","year":2025,"journal":"Journal of clinical medicine, 14(7)","doi":"10.3390/jcm14072239","pmid":"40217690","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"All five included studies showed consistent systolic blood pressure reductions with oral semaglutide, ranging from -2.60 to -12.74 mmHg. Diastolic blood pressure effects were less consistent. Total cholesterol was reduced across all studies (-8.80 to -22.19 mg/dL). Four of five studies reported favorable LDL cholesterol reductions (-7.6 to -18.0 mg/dL) and triglyceride reductions (-11.00 to -40.13 mg/dL).\n\nHDL cholesterol showed the least consistent pattern: three studies found a non-significant increasing trend, while one reported a mild increase. The authors concluded that oral semaglutide may offer cardiovascular benefits comparable to subcutaneous semaglutide, with the advantage of improved patient adherence.","whyItMatters":"Cardiovascular disease is the leading cause of death in type 2 diabetes patients. Injectable semaglutide has proven cardiovascular benefits, but many patients resist or struggle with injections. If the oral form provides comparable cardiovascular protection, it could significantly expand the number of patients who benefit from this drug — particularly in populations where injection therapy faces cultural or practical barriers.","specificNumbers":"","methodology":"Systematic review following PRISMA guidelines, searching eight databases (Scopus, PubMed, Cochrane Library, and others). Included clinical studies using oral semaglutide added to standard diabetes treatment versus placebo, assessing cardiovascular risk factors prospectively or in RCT design. Five studies met inclusion criteria (2 RCTs, 3 prospective observational). Bias assessed via Newcastle-Ottawa and Jadad scales.","limitations":"Only five studies were included, and three were observational rather than randomized. No meta-analysis was performed due to heterogeneity. The review assessed cardiovascular risk factors (blood pressure, lipids) as surrogate endpoints rather than hard cardiovascular events (heart attacks, strokes, death). Direct head-to-head comparisons of oral versus subcutaneous semaglutide on cardiovascular outcomes are lacking."},{"rthcId":"RPEP-11929","title":"Pipeline for development of acylated peptide based CGRP receptor antagonist with extended half-life for migraine treatment.","authors":"Kristensen, Jens Bjelke; Elster, Lisbeth; Lundh, Morten; Ballarín-González, Borja; Alexopoulou, Flora; Kræmer, Martin; Jensen, Ditte Marie; Leurs, Ulrike; Nielsen, Jens Christian; Hansen, Henrik H; Haanes, Kristian A; Degn, Matilda","year":2025,"journal":"Scientific reports, 15(1), 1870","doi":"10.1038/s41598-024-84547-1","pmid":"39805895","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11930","title":"Sex difference in TRPM3 channel functioning in nociceptive and vascular systems: an emerging target for migraine therapy in females?","authors":"Krivoshein, Georgii; Rivera-Mancilla, Eduardo; MaassenVanDenBrink, Antoinette; Giniatullin, Rashid; van den Maagdenberg, Arn M J M","year":2025,"journal":"The journal of headache and pain, 26(1), 40","doi":"10.1186/s10194-025-01966-9","pmid":"39994546","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11931","title":"Foreign epitope-specific regulatory T cells respond robustly to vaccination and limit Th1 differentiation by conventional T cells specific for the same epitope.","authors":"Krueger, Peter D; Osum, Kevin C; Fife, Brian T; Jenkins, Marc K","year":2025,"journal":"Journal of immunology (Baltimore, Md. : 1950), 214(12), 3345-3356","doi":"10.1093/jimmun/vkaf254","pmid":"41014584","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11932","title":"Beyond Weight Loss: GLP-1 Usage and Appetite Regulation in the Context of Eating Disorders and Psychosocial Processes.","authors":"Krug, Isabel; Dang, An Binh; Portingale, Jade; Li, Yakun; Won, Ying Qing","year":2025,"journal":"Nutrients, 17(23)","doi":"10.3390/nu17233735","pmid":"41374025","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11933","title":"Mechanisms of Glucagon-Like Peptide 1 Receptor Agonist-Induced Facial Lipodystrophy and a Path Toward Prevention.","authors":"Kruglikov, Ilja L","year":2025,"journal":"Journal of cosmetic dermatology, 24(12), e70584","doi":"10.1111/jocd.70584","pmid":"41316800","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11934","title":"A biodegradable suction patch for sustainable transbuccal peptide delivery.","authors":"Krupke, Hanna; Zoratto, Nicole; Rabut, Lucie; Gao, Daniel; Paunović, Nevena; Klein Cerrejon, David; Dehapiot, Benoit; Leroux, Jean-Christophe","year":2025,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 384, 113947","doi":"10.1016/j.jconrel.2025.113947","pmid":"40513668","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11935","title":"Predictors of Response to Treatment With Anti-calcitonin Gene-Related Peptide (CGRP) Antibodies in Real-World Patients With Episodic Migraine: A Two- and Four-Month Prospective Study.","authors":"Krymchantowski, Abouch; Jevoux, Carla; Silva-Néto, Raimundo P; Soares, Adriana A; Pimentel, Maria Lucia Vellutini; Krymchantowski, Ana Gabriela; Júnior, Hilton Mariano da Silva; Cotrik, Ervin Michelstaedter","year":2025,"journal":"Cureus, 17(3), e80345","doi":"10.7759/cureus.80345","pmid":"40206906","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11936","title":"Semaglutide and Tirzepatide in Patients With Heart Failure With Preserved Ejection Fraction.","authors":"Krüger, Nils; Schneeweiss, Sebastian; Fuse, Kenshiro; Matseyko, Sofiya; Sreedhara, Sushama Kattinakere; Hahn, Georg; Schunkert, Heribert; Wang, Shirley V","year":2025,"journal":"JAMA, 334(14), 1255-1266","doi":"10.1001/jama.2025.14092","pmid":"40886075","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In expanded eligibility cohorts reflecting real clinical practice:\n\n- Semaglutide vs sitagliptin (n=58,333): HR 0.58 (95% CI 0.51-0.65) — 42% risk reduction for heart failure hospitalization or all-cause mortality\n- Tirzepatide vs sitagliptin (n=11,257): HR 0.42 (95% CI 0.31-0.57) — 58% risk reduction\n- Tirzepatide vs semaglutide head-to-head (n=28,100): HR 0.86 (95% CI 0.70-1.06) — no statistically meaningful difference\n\nBenchmarking analyses emulating the STEP-HFpEF DM and SUMMIT trials showed high agreement, validating the real-world study design. No substantially increased safety risks were identified.","whyItMatters":"HFpEF accounts for roughly half of all heart failure cases and has had few effective treatments until recently. While early randomized trials of semaglutide and tirzepatide showed promise, they were based on few clinical events. This study provides the first large-scale real-world evidence that these peptide drugs substantially reduce heart failure hospitalization and death — the outcomes that matter most to patients and clinicians. Published in JAMA, this is landmark evidence supporting GLP-1-based therapy for HFpEF.","specificNumbers":"","methodology":"Five cohort studies using national US healthcare claims data (2018-2024). Two studies emulated the STEP-HFpEF DM (semaglutide) and SUMMIT (tirzepatide) randomized trials as benchmarks. Three studies used expanded eligibility criteria to evaluate real-world effectiveness, including a head-to-head comparison. Sitagliptin served as a placebo proxy. Propensity score weighting adjusted for comprehensive pretreatment characteristics. Follow-up was up to 52 weeks. Negative control outcomes, secondary endpoints, subgroups, and sensitivity analyses were prespecified.","limitations":"This is an observational study using insurance claims data, not a randomized controlled trial, so residual confounding is possible despite propensity score adjustment. Sitagliptin was used as a placebo proxy, which may introduce bias if sitagliptin itself has cardiac effects. Claims data may not capture all clinical details, and drug adherence cannot be verified. The tirzepatide cohort is smaller due to its more recent market entry. Follow-up was limited to 52 weeks."},{"rthcId":"RPEP-11937","title":"Relationship between seawater temperature, brain GnRH-like peptide expression, and gonadal development in wild bigfin reef squid (Sepioteuthis lessoniana).","authors":"Kubo, Umina; Jaewoo, Lee; Murata, Ryosuke; Aoshima, Takashi; Mushirobira, Yuji; Soyano, Kiyoshi","year":2025,"journal":"Biological research, 58(1), 46","doi":"10.1186/s40659-025-00626-1","pmid":"40604884","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11938","title":"Genetic migraine disorders and the response to calcitonin gene-related peptide antagonist treatment.","authors":"Kuczynski, Andrea M; Kingston, William S","year":2025,"journal":"Headache, 65(6), 1041-1043","doi":"10.1111/head.14942","pmid":"40341526","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11939","title":"Role of NPPB for recovery post ventricular assist device in paediatric dilated cardiomyopathy: Single-cell multiomics.","authors":"Kugo, Yosuke; Kawamura, Takuji; Harada, Akima; Tominaga, Yuji; Miki, Kenji; Ishida, Hidekazu; Ueno, Takayoshi; Miyagawa, Shigeru","year":2025,"journal":"ESC heart failure, 12(6), 4463-4474","doi":"10.1002/ehf2.15430","pmid":"41116329","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11940","title":"Current status of peptide receptor radionuclide therapy in grade 1 and 2 gastroenteropancreatic neuroendocrine tumours.","authors":"Kuiper, Jelka; Zoetelief, Eline; Brabander, Tessa; de Herder, Wouter W; Hofland, Johannes","year":2025,"journal":"Journal of neuroendocrinology, 37(3), e13469","doi":"10.1111/jne.13469","pmid":"39563515","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11941","title":"Tirzepatide for Obstructive Sleep Apnea: A Novel Therapeutic Promise and the Perioperative Considerations.","authors":"Kukanti, Chandini; Chowdhury, Sumit Roy; Singh, Gyaninder Pal","year":2025,"journal":"Indian journal of otolaryngology and head and neck surgery : official publication of the Association of Otolaryngologists of India, 77(6), 2430-2432","doi":"10.1007/s12070-025-05485-6","pmid":"40420878","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11942","title":"A novel bioactive peptide-peptoid hybrid of alpha-calcitonin gene-related peptide protects against pressure-overload induced heart failure.","authors":"Kumar, Ambrish; Deloach, Sarah; Williams, Lernix; DiPette, Donald J; Potts, Jay D","year":2025,"journal":"Frontiers in pharmacology, 16, 1692472","doi":"10.3389/fphar.2025.1692472","pmid":"41293249","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11943","title":"MASLD Pharmacotherapy: Current Standards, Emerging Treatments, and Practical Guidance for Indian Physicians.","authors":"Kumar, Ashish","year":2025,"journal":"The Journal of the Association of Physicians of India, 73(7), e45-e60","doi":"10.59556/japi.73.1058","pmid":"40836732","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies several pharmacological agents showing encouraging clinical trial results for MASLD treatment: resmetirom (a thyroid hormone receptor-β agonist), GLP-1 receptor agonists like semaglutide, PPAR agonists (pioglitazone, saroglitazar), SGLT2 inhibitors, and vitamin E. Emerging therapies including tirzepatide (dual incretin agonist) and FGF analogs are highlighted as potentially transformative.\n\nA structured treatment algorithm for non-cirrhotic MASLD (F0-F3 fibrosis) is presented, incorporating only drugs available in India and stratified by diabetes status and fibrosis severity.","whyItMatters":"MASLD affects a large and growing portion of the global population, driven by rising obesity and diabetes rates. With peptide-based therapies like GLP-1 receptor agonists and dual incretin agonists emerging as key treatment options, this review helps contextualize how these peptide drugs fit into the broader treatment landscape for a major liver disease.","specificNumbers":"","methodology":"This is a narrative review that synthesizes evidence from clinical trials and current literature on MASLD pharmacotherapy. The authors developed a practical treatment algorithm based on available evidence, tailored specifically for clinical use in India considering drug availability, cost-effectiveness, and real-world feasibility.","limitations":"As a narrative review, it does not include a systematic search methodology or meta-analysis. The treatment algorithm is tailored for India and may not directly apply to other healthcare settings. The review focuses on drugs available in India, potentially omitting therapies accessible elsewhere. Long-term safety and efficacy data for many emerging agents remain limited."},{"rthcId":"RPEP-11944","title":"Exploring the Frontiers of Diabetes Vaccination.","authors":"Kumar, Mithilesh; Wasnik, Apoorva; Sagar, Vidya; Priya, Neha; Kujur, Anit; Kumar, Dewesh","year":2025,"journal":"Indian journal of community medicine : official publication of Indian Association of Preventive & Social Medicine, 50(5), 729-732","doi":"10.4103/ijcm.ijcm_248_24","pmid":"41017880","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies several categories of diabetes vaccine candidates currently under investigation:\n\n1. IA-2 peptide vaccines — targeting the autoimmune destruction of beta cells in Type 1 diabetes by inducing immune tolerance to islet autoantigens.\n2. Incretin-based vaccines — designed to enhance the body's GLP-1 signaling for long-lasting glucose regulation in Type 2 diabetes.\n3. Glucose-regulating vaccines — targeting inflammatory and insulin resistance pathways.\n4. Protein-based vaccines — using various protein antigens to modulate immune responses relevant to diabetes.\n\nThese approaches target different disease mechanisms including autoimmunity, inflammation, and insulin resistance across both Type 1 and Type 2 diabetes.","whyItMatters":"Diabetes affects over 500 million people worldwide and current treatments manage symptoms rather than addressing root causes. A successful diabetes vaccine could transform the disease from a lifelong condition requiring daily management into something preventable or even reversible. The peptide-based approaches are particularly interesting because they could potentially retrain the immune system to stop the autoimmune attack that causes Type 1 diabetes, or provide long-lasting incretin enhancement for Type 2 diabetes.","specificNumbers":"","methodology":"This is a narrative review published in the Indian Journal of Community Medicine, summarizing current research efforts in diabetes vaccine development. The review covers target antigens, mechanisms of action, and the current research status of various vaccine approaches.","limitations":"The review is brief (4 pages) and provides a high-level overview rather than a detailed systematic analysis. Most vaccine candidates described are in very early stages of development, with limited clinical data. The review does not critically evaluate the feasibility or timelines for clinical translation. The diverse mechanisms of diabetes make a single vaccine solution unlikely — different vaccine approaches may be needed for different patient populations."},{"rthcId":"RPEP-11945","title":"pLM4CPPs: Protein Language Model-Based Predictor for Cell Penetrating Peptides.","authors":"Kumar, Nandan; Du, Zhenjiao; Li, Yonghui","year":2025,"journal":"Journal of chemical information and modeling, 65(3), 1128-1139","doi":"10.1021/acs.jcim.4c01338","pmid":"39878455","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"pLM4CPPs outperformed existing state-of-the-art CPP prediction models with improvements of 4.9-5.5% in accuracy, 9.3-10.2% in Matthews correlation coefficient, and 14.1-19.6% in sensitivity.\n\nAmong the protein language models tested, ESM-1280 achieved 89.6% accuracy with 97.8% specificity, while ProtT5-XL BFD showed the best overall performance with 90.1% accuracy, 80.2% MCC, 88.5% sensitivity, and 91.7% specificity. The consensus approach combining multiple models further enhanced prediction reliability. The tool is freely available as a web server and open-source code on GitHub.","whyItMatters":"Cell-penetrating peptides are key tools for intracellular drug delivery, but discovering them experimentally is slow and expensive. A more accurate prediction tool allows researchers to prioritize the most promising candidates for lab testing, accelerating the development of peptide-based drug delivery systems for cancer therapy, gene therapy, and other applications where getting drugs inside cells is the bottleneck.","specificNumbers":"","methodology":"Researchers evaluated peptide sequence embeddings from nine pretrained protein language models (BEPLER, CPCProt, SeqVec, ESM variants, ProtT5 variants, ProtBERT). They developed a deep learning architecture using convolutional neural networks (CNNs) for binary classification of CPPs versus non-CPPs. Performance was evaluated on benchmark datasets and compared against existing state-of-the-art CPP prediction methods using accuracy, MCC, sensitivity, and specificity metrics.","limitations":"The tool predicts cell penetration based on sequence alone, without accounting for experimental conditions, peptide modifications, or the specific cell type being targeted. Benchmark dataset quality and representativeness affect model generalizability. The predictions have not been prospectively validated in wet-lab experiments. The sensitivity, while improved, still means some true CPPs will be missed. The web server's long-term availability depends on maintained hosting."},{"rthcId":"RPEP-11946","title":"Are Glucagon-Like Peptide 1 Receptor Agonists and Bariatric Surgery the Answer to Childhood Obesity?","authors":"Kumar, Seema; Olson, Ole; Kellogg, Todd A","year":2025,"journal":"Current atherosclerosis reports, 27(1), 112","doi":"10.1007/s11883-025-01347-2","pmid":"41205002","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11947","title":"Prospective, Matched Case-Control Study of Endoscopic Sleeve Gastroplasty and Semaglutide in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease at One Year.","authors":"Kumar, Sonal; Lahooti, Ali; Hajifathalian, Kaveh; Critelli, Brian; Hassan, Amier; Johnson, Kate E; Baig, Muhammad U; Akagbosu, Cynthia; Canakis, Andrew; Hassan, Kamal; Lahooti, Ila; Dawod, Qais; Wong, Rochelle; Buckholz, Adam; Newberry, Carolyn; Sampath, Kartik; Carr-Locke, David; Mahadev, SriHari; Sharaiha, Reem Z","year":2025,"journal":"Digestive diseases and sciences, 70(11), 3922-3928","doi":"10.1007/s10620-025-09218-1","pmid":"40629230","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11948","title":"Comparative Effects of Liraglutide-R-Alpha Lipoic Acid Combination and Donepezil on Diazepam-Induced Amnesia in Rats.","authors":"Kumar, Sonu; Kumar, Hansraj; Mudgal, Shiv K; Kumar, Subodh; Singh, Harminder","year":2025,"journal":"Cureus, 17(7), e87148","doi":"10.7759/cureus.87148","pmid":"40755635","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11949","title":"Recent advances in peptide-based self-assembled and metal coordinated nanocarriers for targeted cancer drug delivery.","authors":"Kumar, Vijay Bhooshan","year":2025,"journal":"European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 217, 114897","doi":"10.1016/j.ejpb.2025.114897","pmid":"41083060","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Self-assembled peptide nanostructures represent a versatile platform for cancer drug delivery with several key advantages: they can encapsulate both hydrophobic and hydrophilic drugs, they can be engineered with stimuli-responsive elements for site-specific drug release, and they offer improved selectivity for tumor tissue over healthy tissue.\n\nMetal-coordinated peptide assemblies add further capabilities by enhancing structural stability, enabling triggered release of anticancer therapeutics, and addressing limitations of conventional peptide self-assembly. Both linear and cyclic peptide architectures are being explored for these applications.","whyItMatters":"Current chemotherapy drugs are highly toxic and damage healthy cells alongside cancer cells, causing severe side effects. Peptide-based nanocarriers could change this by wrapping drugs in biocompatible packages that preferentially accumulate in tumors and release their payload in response to tumor-specific conditions (like acidity or enzymes). Because peptides are made from natural amino acids, they tend to be well-tolerated and biodegradable, making them attractive alternatives to synthetic polymer-based delivery systems.","specificNumbers":"","methodology":"This is a comprehensive review article surveying recent literature on self-assembled peptide nanomaterials for cancer drug delivery. The review covers design strategies using linear and cyclic peptides, the role of metal coordination in enhancing delivery performance, stimuli-responsive release mechanisms, and current challenges and innovations in the field.","limitations":"As a review article, no new experimental data is presented. Most peptide self-assembly drug delivery systems described are at the preclinical stage, with limited clinical translation to date. Key challenges include manufacturing scalability, batch-to-batch consistency, in vivo stability, and regulatory hurdles. The review may overemphasize promising results while underrepresenting the many systems that have failed to advance."},{"rthcId":"RPEP-11950","title":"Luminescent ultrashort peptide hydrogelator with enhanced photophysical implications and biocompatibility.","authors":"Kumari, Aanchal; Bangal, Gitanjali; Das, Basab Kanti; Baroi, Malay Kumar; Kumari, Mamta; Das, Priyanka; Reddy, Kolimi Prashanth; Islam, Rakibul; Dhaked, Devendra Kumar; Pramanik, Bapan; Roy, Subhadeep; Ahmed, Sahnawaz","year":2025,"journal":"Journal of materials chemistry. B, 13(14), 4406-4418","doi":"10.1039/d4tb02687j","pmid":"40094482","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11951","title":"Effects of Surface Charge of Amphiphilic Peptides on Peptide-Lipid Interactions in the Gas Phase and in Solution.","authors":"Kundlacz, Til; Schwieger, Christian; Schmidt, Carla","year":2025,"journal":"Analytical chemistry, 97(10), 5808-5817","doi":"10.1021/acs.analchem.5c00283","pmid":"40052744","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11952","title":"Semaglutide-Induced Hepatic Injury: A Rare Case of Drug Induced Liver Injury.","authors":"Kundu, Rupayan; Shtoff, Lyudmila","year":2025,"journal":"Clinical case reports, 13(8), e70783","doi":"10.1002/ccr3.70783","pmid":"40771557","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A middle-aged male with well-controlled type 2 diabetes and social alcohol use developed asymptomatic elevations in ALT and AST while taking semaglutide. A comprehensive workup — including undetectable blood ethanol, normal viral hepatitis panel, and unremarkable liver ultrasound — found no alternative cause.\n\nAfter semaglutide was discontinued, transaminase levels declined rapidly, supporting a diagnosis of drug-induced liver injury (DILI). The mechanism remains unclear but may involve idiosyncratic metabolic stress, weight loss effects, or biliary dysfunction.","whyItMatters":"As semaglutide use explodes for diabetes and weight loss, identifying rare adverse effects is critical for patient safety. This case reminds clinicians to monitor liver enzymes and consider semaglutide as a potential cause of unexplained liver injury, even though the drug is generally considered hepatoprotective.","specificNumbers":"","methodology":"This is a single case report. The patient underwent standard clinical workup including liver enzyme panels, blood ethanol level, viral hepatitis screening, and liver ultrasound. The temporal relationship between semaglutide use, enzyme elevation, drug discontinuation, and enzyme normalization was used to establish a likely causal link.","limitations":"This is a single case report, the weakest form of clinical evidence. It cannot prove causation — only temporal association. The patient had social alcohol use, which could theoretically contribute despite undetectable ethanol at presentation. No liver biopsy was performed to confirm the mechanism, and no rechallenge was attempted."},{"rthcId":"RPEP-11953","title":"Peptide Receptor Radionuclide Therapy with Lu-177-DOTATATE and Monitoring with Somatostatin Receptor PET/CT in Patients with Advanced Differentiated Thyroid Carcinoma.","authors":"Kunte, Sophie Carina; Wenter, Vera U; Holzgreve, Adrien; Sheikh, Gabriel T; Widjaja, Liam; Gildehaus, Franz Josef; Lindner, Simon; Schirrmacher, Ralf; Spitzweg, Christine; Auernhammer, Christoph J; Werner, Rudolf A; Zacherl, Mathias J","year":2025,"journal":"Molecular imaging and biology, 27(6), 954-965","doi":"10.1007/s11307-025-02053-w","pmid":"41023438","tags":["peptide-imaging","somatostatin-analogs"],"studyType":"observational-study","evidenceStrength":"preliminary","keyFinding":"Lu-177-DOTATATE peptide receptor radionuclide therapy (PRRT) — normally used for neuroendocrine tumors — showed promising results in 7 patients with advanced thyroid cancer that no longer responded to radioiodine. SSTR PET scans confirmed high somatostatin receptor uptake in metastases (SUVmax 10.4 ± 8.6), particularly in bone.\n\nAmong 5 patients receiving continuous PRRT, 60% achieved tumor control by volume and RECIST criteria. The 2 patients who had treatment breaks still showed stable disease at follow-up, and when PRRT was restarted, their tumors responded again — suggesting the treatment remains effective even after interruption. No severe adverse events (Grade 3-5) occurred in either group.","whyItMatters":"When thyroid cancer stops responding to radioiodine — the standard targeted therapy — treatment options become limited. This small study suggests that peptide-based radiation therapy, already proven in neuroendocrine tumors, may offer a new option for these patients. The finding that PRRT can be stopped and restarted while maintaining effectiveness is particularly encouraging for long-term management.","specificNumbers":"n=7 patients · ≥2 PRRT cycles each · SUVmax 10.4 ± 8.6 · 60% tumor control (continuous group) · 100% stable disease at first follow-up (discontinuous group) · 0 Grade 3-5 adverse events","methodology":"Retrospective analysis of 7 patients with radioiodine-refractory differentiated thyroid carcinoma who received at least 2 cycles of Lu-177-DOTATATE PRRT. Patients were subdivided into continuous treatment (5 patients) and discontinuous treatment with at least a one-year gap (2 patients). Tumor response was assessed using PET-derived total tumor volume, thyroglobulin levels, and RECIST 1.1 criteria. Adverse events were graded using CTCAE.","limitations":"With only 7 patients, this is a very small case series — the smallest meaningful cohort to report. The retrospective design limits causal conclusions. There was no control group for comparison. The variable treatment schedules make it difficult to determine optimal PRRT protocols for thyroid cancer. Longer follow-up is needed to assess durability of responses."},{"rthcId":"RPEP-11954","title":"Glucagon-like peptide-1 receptor agonists and gastrointestinal cancer risk in individuals with type 2 diabetes.","authors":"Kuo, Chia-Chih; Chuang, Min-Hsiang; Li, Chun-Hsien; Tsai, Ya-Wen; Huang, Po-Yu; Kuo, Hsing-Tao; Lai, Chih-Cheng","year":2025,"journal":"Diabetologia, 68(9), 1924-1936","doi":"10.1007/s00125-025-06453-z","pmid":"40471238","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11955","title":"Impact of GLP-1 Receptor Agonists on Alcohol-Related Liver Disease Development and Progression in Alcohol Use Disorder.","authors":"Kuo, Chia-Chih; Li, Chun-Hsien; Chuang, Min-Hsiang; Huang, Po-Yu; Kuo, Hsing-Tao; Lai, Chih-Cheng","year":2025,"journal":"Alimentary pharmacology & therapeutics, 61(8), 1343-1356","doi":"10.1111/apt.70007","pmid":"39891379","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11956","title":"Semaglutide and the risk of adverse liver outcomes in patients with nonalcoholic fatty liver disease and type 2 diabetes: a multi-institutional cohort study.","authors":"Kuo, Chia-Chih; Chuang, Min-Hsiang; Li, Chun-Hsien; Huang, Po-Yu; Kuo, Hsing-Tao; Lai, Chih-Cheng","year":2025,"journal":"Hepatology international, 19(2), 395-404","doi":"10.1007/s12072-024-10752-9","pmid":"39602049","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11957","title":"Semaglutide versus other GLP-1 receptor agonists in patients with MASLD.","authors":"Kuo, Chia-Chih; Li, Chun-Hsien; Chuang, Min-Hsiang; Huang, Po-Yu; Kuo, Hsing-Tao; Lai, Chih-Cheng","year":2025,"journal":"Hepatology communications, 9(7)","doi":"10.1097/HC9.0000000000000747","pmid":"40536520","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11958","title":"The protective effects of liraglutide in reducing lipid droplets accumulation and myocardial fibrosis in diabetic cardiomyopathy.","authors":"Kuo, Chien-Yin; Tsou, Sing-Hua; Kornelius, Edy; Chan, Kuei-Chuan; Chang, Kai-Wei; Li, Jung-Chi; Huang, Chien-Ning; Lin, Chih-Li","year":2025,"journal":"Cellular and molecular life sciences : CMLS, 82(1), 39","doi":"10.1007/s00018-024-05558-9","pmid":"39779525","tags":[],"studyType":"animal-and-cell","evidenceStrength":"low","keyFinding":"Liraglutide significantly reduced lipid droplet accumulation and myocardial fibrosis in both cell and mouse models of diabetic cardiomyopathy. The drug decreased expression of fibrosis markers TGF-β1, collagen I, and collagen III. It achieved these protective effects by activating AMPK, which improved mitochondrial function, boosted antioxidant gene expression, enhanced insulin signaling, and reduced oxidative stress in heart cells.","whyItMatters":"Diabetic cardiomyopathy is a major cause of heart failure in people with diabetes, and there are currently no specific approved treatments for it. This study reveals a detailed molecular mechanism by which liraglutide — already used for diabetes and obesity — could protect the heart from diabetes-related damage, potentially adding cardioprotection to its existing benefits.","specificNumbers":"Decreased TGF-β1, collagen I, collagen III · Increased AMPK activation · Improved mitochondrial function · Reduced oxidative stress · Both in vitro and in vivo models","methodology":"Combined cell culture and animal study. Differentiated H9c2 heart cells were treated with high glucose and free fatty acids to mimic diabetic conditions, then treated with liraglutide. A mouse model of diabetic cardiomyopathy was created using high-fat diets. Both models assessed lipid droplet formation, fibrosis markers, AMPK signaling, mitochondrial function, antioxidant gene expression, and oxidative stress.","limitations":"This is a preclinical study using cell lines and mice, not human patients. The H9c2 cells are rat-derived and may not fully represent human cardiomyocyte biology. The molecular mechanisms identified need to be validated in human cardiac tissue. The study does not report functional cardiac outcomes (e.g., ejection fraction, cardiac output)."},{"rthcId":"RPEP-11959","title":"Dissecting Hidden Liraglutide Oligomerization Pathways via Direct Mass Technology, Electron-Capture Dissociation, and Molecular Dynamics.","authors":"Kuo, Syuan-Ting; Xi, Zhenyu; Cong, Xiao; Yan, Xin; Russell, David H","year":2025,"journal":"Analytical chemistry, 97(25), 13465-13473","doi":"10.1021/acs.analchem.5c01851","pmid":"40521838","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11960","title":"Unveiling the Hidden: Dissecting Liraglutide Oligomerization Dual Pathways via Direct Mass Technology, Electron-Capture Dissociation, and Molecular Dynamics.","authors":"Kuo, Syuan-Ting; Xi, Zhenyu; Cong, Xiao; Yan, Xin; Russell, David H","year":2025,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2025.02.27.640645","pmid":"40093118","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11961","title":"Associations of N-Terminal Pro-Brain Natriuretic Peptide with Incident Chronic Kidney Disease and All-Cause Mortality in Patients with No History of Heart Failure and Diabetes.","authors":"Kuo, Y N; Lin, C H; Wang, J S","year":2025,"journal":"Nigerian journal of clinical practice, 28(12), 1470-1477","doi":"10.4103/njcp.njcp_567_25","pmid":"41459901","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 197 patients without heart failure or diabetes followed for a median of 10.6 years, NT-proBNP >125 pg/mL was associated with a 2.54-fold increased risk (HR 2.54, 95% CI 1.34-4.82, p=0.004) of developing chronic kidney disease (eGFR <60 mL/min/1.73 m²) or dying from any cause. After multivariate adjustment, the association remained significant (adjusted HR 2.23, 95% CI 1.10-4.52, p=0.026), confirming NT-proBNP as an independent predictor of renal and mortality outcomes.","whyItMatters":"NT-proBNP is widely available and routinely measured in clinical practice for heart failure. Discovering that this peptide biomarker also independently predicts kidney disease and death in people without heart failure or diabetes means it could be used as a broader screening tool for identifying high-risk patients who might benefit from early preventive intervention.","specificNumbers":"","methodology":"This was a prospective cohort study enrolling patients without diabetes who underwent oral glucose tolerance testing between 2011 and 2013. Patients with heart failure or existing CKD (eGFR <60) were excluded. NT-proBNP was measured at baseline and dichotomized at 125 pg/mL. Cox proportional hazards models assessed the association with composite outcome of incident CKD and all-cause mortality over a median 10.6-year follow-up.","limitations":"The sample size of 197 patients is small, limiting statistical power and the ability to adjust for multiple confounders. The study combined CKD incidence and all-cause mortality as a composite endpoint, making it difficult to assess each outcome independently. The single-center design and specific population (patients undergoing glucose tolerance testing) may limit generalizability. Repeat NT-proBNP measurements were not assessed."},{"rthcId":"RPEP-11962","title":"Dulaglutide and pregnancy: a comprehensive safety assessment using the ex vivo placenta perfusion and in vitro models.","authors":"Kuoni, Sabrina; Caviglia, Sara; Dolder, Alexandra; Gawinecka, Joanna; Ochsenbein-Kölble, Nicole; Simões-Wüst, Ana Paula","year":2025,"journal":"Frontiers in pharmacology, 16, 1765815","doi":"10.3389/fphar.2025.1765815","pmid":"41640683","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11963","title":"Respiratory tract antimicrobial peptides more effectively killed multiple methicillin-resistant Staphylococcus aureus and nontypeable Haemophilus influenzae isolates after disruption from biofilm residence.","authors":"Kurbatfinski, Nikola; Jurscisek, Joseph A; Wilbanks, Kathryn Q; Goodman, Steven D; Bakaletz, Lauren O","year":2025,"journal":"Microbiology spectrum, 13(8), e0306624","doi":"10.1128/spectrum.03066-24","pmid":"40530663","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Three isolates each of MRSA and nontypeable Haemophilus influenzae (NTHI), when released from biofilms using an anti-DNABII monoclonal antibody, became significantly more sensitive to killing by three respiratory antimicrobial peptides: human β-defensin 1 (hBD-1), human β-defensin 3 (hBD-3), and the cathelicidin LL-37.\n\nThis vulnerability is a transient phenotype linked to increased membrane permeability in newly released bacteria. In three animal models of biofilm infections, the DNABII-directed monoclonal antibody alone (without co-delivered antibiotics) induced biofilm disruption with rapid bacterial clearance and disease resolution, suggesting that innate immune effectors including antimicrobial peptides drive the clearance.","whyItMatters":"Biofilm-mediated infections (ear infections, sinusitis, urinary tract infections, wound infections) affect hundreds of millions worldwide and are among the hardest to treat. Current antibiotics fail because biofilm bacteria are inherently resistant. This approach leverages the body's own antimicrobial peptide arsenal by first removing the biofilm shield, potentially eliminating the need for antibiotics and addressing antimicrobial resistance.","specificNumbers":"","methodology":"Biofilms of three MRSA and three NTHI isolates were formed in vitro and then disrupted using a monoclonal antibody targeting DNABII proteins in the biofilm matrix. Newly released bacteria were tested for sensitivity to hBD-1, hBD-3, and LL-37. Prior animal model data from three infection models was referenced to support the clinical relevance of the approach.","limitations":"The antimicrobial peptide sensitivity testing was performed in vitro, which may not fully replicate the complex environment of the respiratory tract. The newly released phenotype is transient, meaning timing of immune response is critical. Only three isolates of each species were tested. While animal models showed clearance without antibiotics, human immune status varies and immunocompromised patients may not respond similarly. The monoclonal antibody is still in preclinical/early clinical development."},{"rthcId":"RPEP-11964","title":"Serum ACE2 activity as a novel biomarker of assessment of severe aortic stenosis.","authors":"Kurczina, Anita; Ráduly, Arnold Péter; Siket, Ivetta Mányiné; Pólik, Zsófia; Kracskó, Bertalan; Kertész, Attila Béla; Balogh, Ágnes; Molnár, Andrea; Fülöp, Tibor; Antal, Laura; Ötvös, Csaba; Fagyas, Miklós; Szerafin, Tamás; Tóth, Attila; Papp, Zoltán; Csanádi, Zoltán; Borbély, Attila","year":2025,"journal":"GeroScience","doi":"10.1007/s11357-025-01792-6","pmid":"40665095","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11965","title":"Clinical Factors Associated with Body-weight Reduction Induced by Semaglutide 1.0 mg Weekly in Patients with Type 2 Diabetes Mellitus.","authors":"Kurinami, Noboru; Takada, Masafumi; Ashida, Kenji; Sugiyama, Seigo; Yoshida, Akira; Hieshima, Kunio; Suzuki, Tomoko; Miyamoto, Fumio; Kajiwara, Keizo; Jinnouchi, Katsunori; Nomura, Masatoshi; Jinnouchi, Hideaki","year":2025,"journal":"JMA journal, 8(2), 526-532","doi":"10.31662/jmaj.2024-0366","pmid":"40416014","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11966","title":"Early Dose Escalation of Tirzepatide after Switching from Semaglutide in Type 2 Diabetes Mellitus.","authors":"Kurinami, Noboru; Takada, Masafumi; Sugiyama, Seigo; Yoshida, Akira; Hieshima, Kunio; Suzuki, Tomoko; Miyamoto, Fumio; Kajiwara, Keizo; Jinnouchi, Katsunori; Ashida, Kenji; Nomura, Masatoshi; Jinnouchi, Hideaki","year":2025,"journal":"Endocrinology and metabolism (Seoul, Korea), 40(6), 1012-1015","doi":"10.3803/EnM.2025.2420","pmid":"41088952","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11967","title":"Membrane Repair Proteins as Negative Regulators of Cytosolic Delivery Using Attenuated Cationic Lytic Peptide L17E and Cell-Penetrating Peptides: Differences and Similarities.","authors":"Kuriyama, Masashi; Kawaguchi, Yoshimasa; Ito, Shinji; Satoh, Junko; Hirose, Hisaaki; Futaki, Shiroh","year":2025,"journal":"Bioconjugate chemistry, 36(8), 1683-1697","doi":"10.1021/acs.bioconjchem.5c00177","pmid":"40730879","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11968","title":"Controlling Joint Instability Reduces Inflammatory Pain in Early Knee Osteoarthritis.","authors":"Kuroo, Aya; Murata, Kenji; Morishita, Yuri; Onitsuka, Katsuya; Oka, Yuichiro; Tanaka, Ken-Ichi; Kanemura, Naohiko","year":2025,"journal":"Cureus, 17(7), e87711","doi":"10.7759/cureus.87711","pmid":"40786277","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11969","title":"New aspect on the regulation of in vitro oocyte maturation: role of the obesity, neuropeptides and adipokines.","authors":"Kurowska, Patrycja; Wyroba, Jakub; Pich, Karolina; Respekta-Długosz, Natalia; Szkraba, Oliwia; Greggio, Aleksandra; Kochan, Joanna; Rak, Agnieszka","year":2025,"journal":"Journal of assisted reproduction and genetics, 42(3), 737-752","doi":"10.1007/s10815-024-03345-w","pmid":"39671071","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11970","title":"Cannabinoids in headache: helpful or harmful?","authors":"Kuruvilla, Deena E","year":2025,"journal":"Current opinion in neurology, 38(3), 277-280","doi":"10.1097/WCO.0000000000001364","pmid":"40152937","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11971","title":"Understanding migraine throughout a woman's life and the role of calcitonin gene-related peptide: A narrative review.","authors":"Kuruvilla, Deena E; Hutchinson, Susan; Moriarty, Maureen; Abbott, Chandra; Brown, Audrey; Leroue, Chelsea; Sheikh, Huma","year":2025,"journal":"Women's health (London, England), 21, 17455057251376878","doi":"10.1177/17455057251376878","pmid":"41109841","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11972","title":"Clinician Guidance on the Benefits of Healthy Nutrition and Increased Physical Activity for People With Type 2 Diabetes Following Glucagon-Like Peptide 1 Receptor Agonist Initiation.","authors":"Kushner, Pamela; Campos, Carlos; King, Aaron; Kruger, Davida F; Morales, Javier","year":2025,"journal":"Clinical diabetes : a publication of the American Diabetes Association, 43(5), 681-695","doi":"10.2337/cd25-0037","pmid":"41438314","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11973","title":"Safety profile of semaglutide versus placebo in the SELECT study: a randomized controlled trial.","authors":"Kushner, Robert F; Ryan, Donna H; Deanfield, John; Kokkinos, Alexander; Cercato, Cintia; Wilding, John; Burguera, Bartolome; Wu, Chau-Chung; Craciun, Anca-Elena; Pall, Denes; Hramiak, Irene; Hjelmesæth, Jøran; Harder-Lauridsen, Nina M; Weimers, Petra; Jeppesen, Ole Kleist; Kallenbach, Klaus; Lincoff, A Michael; Lingvay, Ildiko","year":2025,"journal":"Obesity (Silver Spring, Md.), 33(3), 452-462","doi":"10.1002/oby.24222","pmid":"39948761","tags":["glp-1-agonists","semaglutide"],"studyType":"Randomized Controlled Trial (Safety Analysis)","evidenceStrength":"strong","keyFinding":"In the massive SELECT cardiovascular outcomes trial, semaglutide 2.4 mg weekly was actually safer overall than placebo for serious adverse events: 33.4% of semaglutide patients had SAEs versus 36.4% on placebo (p<0.001), driven largely by fewer cardiac events (11.5% vs 13.5%).\n\nHowever, more patients stopped semaglutide due to side effects (16.6% vs 8.2%), with gastrointestinal problems being the main reason (10.0% vs 2.0%). Gallbladder disorders were slightly more common with semaglutide (2.8% vs 2.3%, p=0.04), mainly gallstones rather than inflammation. Crucially, suicide and self-injury rates were identical and very low in both groups (0.11%). No new safety concerns were identified.","whyItMatters":"SELECT is the largest and longest cardiovascular outcomes trial of semaglutide in people with obesity. This safety analysis provides the most definitive long-term safety data available — critically important given that tens of millions of people are now taking this drug. The finding that semaglutide actually reduced serious adverse events compared to placebo is reassuring, and the suicide/self-injury data directly addresses a widely publicized safety concern.","specificNumbers":"SAEs: 33.4% semaglutide vs 36.4% placebo (p<0.001) · cardiac SAEs: 11.5% vs 13.5% · discontinuation: 16.6% vs 8.2% · GI discontinuation: 10.0% vs 2.0% · gallbladder: 2.8% vs 2.3% · suicide/self-injury: 0.11% both groups","methodology":"Pre-specified safety analysis from the SELECT randomized controlled trial. Patients with established cardiovascular disease and overweight/obesity received semaglutide 2.4 mg or placebo once weekly. Researchers analyzed serious adverse events, all adverse events leading to treatment discontinuation, and prespecified adverse events of special interest. Two-sided p-values were used for treatment comparisons.","limitations":"The study population had established cardiovascular disease — results may not generalize to healthier obesity patients. The mean treatment duration is not specified in the abstract. Patients who discontinued due to GI side effects may have self-selected out early, potentially underestimating long-term GI burden. Industry-sponsored (Novo Nordisk)."},{"rthcId":"RPEP-11974","title":"Prognostic significance of natriuretic peptides after transcatheter aortic valve replacement: A systematic review and meta-analysis.","authors":"Kushnir, Yevhen; Barrera, Nelson; Romero, Erick; Alam, Usman; Statnii, Iurii; Golovataya, Kristina; Tole, Maria Camila; Bortnick, Anna E","year":2025,"journal":"medRxiv : the preprint server for health sciences","doi":"10.64898/2025.12.02.25341522","pmid":"41409682","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11975","title":"Evaluating the Role of Baseline Brain Natriuretic Peptide in Predicting Heart Failure Post-acute Coronary Syndrome: Systematic Review and Meta-analysis.","authors":"Kusumowardani, Alivia Retra; Yudhisthira, Narendra Lintang","year":2025,"journal":"Heart views : the official journal of the Gulf Heart Association, 26(2), 116-125","doi":"10.4103/heartviews.heartviews_125_24","pmid":"41170140","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 10 studies, the meta-analysis found:\n\n- Patients who developed heart failure post-ACS had significantly higher baseline BNP levels (standardized mean difference: 0.95, 95% CI: 0.54–1.37, p<0.001)\n- However, the odds ratio for HF occurrence based on baseline BNP was not significant (OR: 1.83, 95% CI: 0.11–29.07, p=0.67)\n- 8 of 10 individual studies showed a positive association between baseline BNP and post-ACS heart failure\n\nThis discrepancy suggests that while BNP is elevated in those who develop HF, the variation between studies is too large for a single cutoff to be clinically useful.","whyItMatters":"Heart failure after a heart attack is common and deadly, but early identification of at-risk patients could allow preventive treatment. BNP is already routinely measured in cardiac care. If baseline BNP could reliably predict post-ACS heart failure, it would require no additional testing — just better use of existing data. This study clarifies that while BNP is informative, it needs to be part of a broader risk assessment strategy.","specificNumbers":"","methodology":"Systematic review and meta-analysis of 10 studies identified from Medline database. Included studies reported baseline BNP values in ACS patients and subsequent heart failure incidence. Both odds ratios (for categorical BNP analysis) and standardized mean differences (for continuous BNP values) were calculated. Statistical analysis was performed using Review Manager.","limitations":"Only 10 studies met inclusion criteria, limiting statistical power. The wide confidence interval for the odds ratio (0.11–29.07) indicates extreme heterogeneity. Different BNP assays, cutoff values, and follow-up durations across studies may explain inconsistent results. Only Medline was searched, potentially missing relevant studies in other databases. The distinction between BNP and NT-proBNP across studies was not addressed in the abstract."},{"rthcId":"RPEP-11976","title":"Oral versus subcutaneous semaglutide weight loss outcomes after two years among patients with type 2 diabetes in a real-world database.","authors":"Kwon, Jimmy; Thiara, Diana; Watanabe, Jonathan H","year":2025,"journal":"Expert review of endocrinology & metabolism, 20(2), 163-168","doi":"10.1080/17446651.2025.2462100","pmid":"39921267","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Over two years, subcutaneous semaglutide users (n=310) lost a mean 7.5% body weight (16.7 pounds), while oral semaglutide users (n=57) lost 4.4% (8.7 pounds) — a statistically significant difference (p<0.01). For the clinically meaningful threshold of ≥10% weight loss, 32.9% of injection users achieved it versus 17.5% of pill users (p=0.03).\n\nThe proportion achieving ≥5% weight loss was not significantly different between formulations (58.7% vs 50.9%, p=0.34). An unexpected finding was an age effect within oral semaglutide users: older patients achieved better weight loss than younger ones (p=0.02), a pattern not seen in the subcutaneous group. Regression analyses adjusting for confounders confirmed these findings.","whyItMatters":"Many patients prefer pills over injections, and oral semaglutide was developed specifically to address this preference. However, this real-world data shows that the convenience of the pill comes with a meaningful trade-off in weight loss effectiveness — patients lose roughly half the weight compared to the injection over two years. This information is crucial for informed shared decision-making between clinicians and patients, particularly when weight loss is a primary treatment goal.","specificNumbers":"","methodology":"This was a retrospective cohort study using a real-world database, comparing adults with type 2 diabetes who received subcutaneous semaglutide (n=310) versus oral semaglutide (n=57) over a 2-year treatment period. Weight loss was evaluated through mean percentage change from baseline and proportion achieving ≥5% and ≥10% weight loss. Results were analyzed by formulation and by age group, with regression analyses adjusting for confounding variables.","limitations":"The oral semaglutide group (n=57) was much smaller than the subcutaneous group (n=310), reducing statistical power for subgroup analyses. As a retrospective observational study, it cannot establish causation — the two groups may differ in unmeasured ways despite regression adjustment. Adherence to the strict oral semaglutide dosing protocol was not measured. The oral semaglutide doses available at the time (up to 14 mg) were lower than the newer 25 mg and 50 mg formulations now in development, which may narrow the efficacy gap. Reasons for choosing oral versus subcutaneous were not captured."},{"rthcId":"RPEP-11977","title":"Effects of LinTT1-peptide conjugation on the properties of poly(ethylene glycol)-block-(ε-caprolactone) nanoparticles prepared by the nanoprecipitation method.","authors":"Känkänen, Voitto; Hirvonen, Sami-Pekka; Teesalu, Tambet; Hirvonen, Jouni; Balasubramanian, Vimalkumar; Santos, Hélder A","year":2025,"journal":"Drug delivery and translational research, 15(8), 2733-2748","doi":"10.1007/s13346-024-01768-7","pmid":"39753999","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Both pre-conjugation and post-conjugation of LinTT1 (AKRGARSTA) to PCL-PEG nanoparticles enabled binding to the target protein p32 in cell-free assays, but only when methyl-terminated PCL-PEG was used as diluent — acid-terminated polymer abolished target binding. Peptide conjugation via maleimide-thiol chemistry was confirmed by GPC and fluorescence. An unexpected morphological transformation from spheres to vesicles occurred upon peptide conjugation regardless of method. The pre-conjugation approach yielded smaller, more homogeneous nanoparticles.","whyItMatters":"Peptide-targeted nanoparticles are a leading strategy for delivering cancer drugs specifically to tumors, reducing side effects. But the devil is in the details — this study shows that seemingly minor formulation choices (like the polymer end-group) can completely make or break tumor targeting. The morphological transformation from spheres to vesicles is also practically important, as particle shape affects how nanoparticles circulate in the body and penetrate tumors.","specificNumbers":"","methodology":"Researchers compared two peptide-nanoparticle conjugation strategies: post-conjugation (attaching LinTT1 to pre-formed nanoparticles) and pre-conjugation (synthesizing peptide-polymer conjugates first, then forming nanoparticles by nanoprecipitation). Characterization included particle size, zeta potential, morphology (TEM), peptide content, and target binding (p32 cell-free assay). Two diluent polymers (methyl-terminated and acid-terminated PCL-PEG) were compared.","limitations":"All testing was performed in cell-free conditions — no cellular uptake, in vivo tumor targeting, or drug delivery studies were conducted. The morphological transformation may affect drug loading capacity and release kinetics, but these weren't evaluated. Only one peptide (LinTT1) and one polymer system (PCL-PEG) were tested. The p32 binding assay doesn't capture the complexity of in vivo tumor targeting."},{"rthcId":"RPEP-11978","title":"Impaired Gustation in Liver Diseases: A Comprehensive Narrative Literature Review.","authors":"Kędziora-Ciechańska, Aleksandra; Ciechański, Krystian; Chałas, Renata","year":2025,"journal":"Acta stomatologica Croatica, 59(4), 426-439","doi":"10.15644/asc59/4/9","pmid":"41585420","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11979","title":"Nanogel encapsulation improves pharmacokinetics and biodistribution of antimicrobial peptide LL37 upon lung deposition: In vivo evaluation by SPECT/CT.","authors":"Kłodzińska, Sylvia N; Esposito, Tullio V F; Agnoletti, Monica; Rodríguez-Rodríguez, Cristina; Blackadar, Colin; Wu, Lan; Thakur, Aneesh; Nahrstedt, Jessica; Rades, Thomas; Saatchi, Katayoun; Häfeli, Urs O; Mørck Nielsen, Hanne","year":2025,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 383, 113817","doi":"10.1016/j.jconrel.2025.113817","pmid":"40339660","tags":["antimicrobial-peptides"],"studyType":"animal","evidenceStrength":"preliminary","keyFinding":"Encapsulating LL-37 (the only human cathelicidin antimicrobial peptide) in hyaluronic acid-based nanogels increased its retention in the lungs by 36% compared to unformulated LL-37 after intratracheal administration. Without nanogel protection, approximately 85% of LL-37 was cleared from the lungs within 48 hours. The nanogel formulation also reduced the amount of peptide reaching the liver and kidneys, potentially decreasing the toxicity risks associated with high-dose antimicrobial peptide therapy.\n\nThe researchers used radiolabeled tracking (67-gallium for LL-37, 111-indium for the nanogel polymer) with SPECT/CT imaging to non-invasively monitor both the peptide and its carrier in real time in mice.","whyItMatters":"Antimicrobial peptides like LL-37 are promising weapons against antibiotic-resistant bacteria, but they break down too quickly in the body and can damage the liver and kidneys at the high doses needed. This nanogel approach solves both problems simultaneously — keeping more peptide in the lungs where it's needed while reducing how much reaches organs where it causes harm. This could make inhaled LL-37 a viable treatment for lung infections.","specificNumbers":"85% of free LL-37 cleared from lungs in 48 hr · Nanogel increased lung retention by 36% · Reduced peptide in liver and kidneys · 67Ga-labeled LL-37 · 111In-labeled HA-OSA nanogel · SPECT/CT tracking in mice","methodology":"Researchers created nanogels from hyaluronic acid modified with octenyl succinic anhydride (HA-OSA) and loaded them with LL-37. Both the peptide and the carrier polymer were radiolabeled with different isotopes, enabling dual-tracked SPECT/CT imaging in mice after intratracheal administration. The biodistribution of LL-37 was compared between nanogel-encapsulated and free peptide over 48 hours, measuring retention in the lungs and accumulation in excretory organs.","limitations":"This is an animal study in mice with pharmacokinetic tracking — it did not test whether the nanogel-formulated LL-37 was actually more effective at killing bacteria in lung infections. The antibacterial efficacy of the encapsulated peptide in vivo was not assessed. Mouse lung anatomy differs from human lungs, and scaling inhaled delivery to humans is challenging."},{"rthcId":"RPEP-11980","title":"Short-term impact of tirzepatide on metabolic hypogonadism and body composition in patients with obesity: a controlled pilot study.","authors":"La Vignera, Sandro; Cannarella, Rossella; Garofalo, Vincenzo; Crafa, Andrea; Barbagallo, Federica; Condorelli, Rosita A; Calogero, Aldo E","year":2025,"journal":"Reproductive biology and endocrinology : RB&E, 23(1), 92","doi":"10.1186/s12958-025-01425-9","pmid":"40604795","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11981","title":"Is GLP-1 receptor agonist therapy safe for patients with intraductal papillary mucinous neoplasm?","authors":"Lagger, Melissa; Irmanesh, Pouya; Frossard, Jean-Louis; Adamina, Michel; Buhler, Leo","year":2025,"journal":"Swiss medical weekly, 155, 4850","doi":"10.57187/s.4850","pmid":"41100817","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11982","title":"Insulin requirements after switching from GLP-1 receptor agonist to dual GIP/GLP-1 receptor agonist in patients with type 2 diabetes mellitus.","authors":"Lahey, Alexa M; Duprey, Karolyn; Montague, Riley C; Schadler, Aric D; Naseman, Kristina W","year":2025,"journal":"Pharmacotherapy, 45(4), 220-226","doi":"10.1002/phar.70009","pmid":"40108854","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11983","title":"A Randomized, Double-Blind, Two-Way Cross-over Study to Evaluate the Efficacy of Liraglutide Treatment in Patients Undergoing Transoral Outlet Reduction Endoscopy for Weight Regain Post Roux-en-Y Gastric Bypass.","authors":"Lahooti, Ali; Hoff, Anna C; Critelli, Brian; Hassan, Amier; Westerveld, Donevan; Hajifathalian, Kaveh; Dawod, Enad; Akagbosu, Cynthia O; Aljohani, Waleed; Hassan, Kamal; Nunes, Gabriel Cairo; Barrichello, Sergio; Neto, Manoel Galvao; Scarparo, Jimi; Newberry, Carolyn; Kumar, Sonal; Sharaiha, Reem Z","year":2025,"journal":"Obesity surgery, 35(3), 775-783","doi":"10.1007/s11695-025-07671-5","pmid":"39885064","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11984","title":"Potential of Kefir-Derived Peptides, Probiotics, and Exopolysaccharides for Osteoporosis Management.","authors":"Lai, Jen-Chieh; Chang, Gary Ro-Lin; Tu, Min-Yu; Cidem, Abdulkadir; Chen, I-Chien; Chen, Chuan-Mu","year":2025,"journal":"Current osteoporosis reports, 23(1), 18","doi":"10.1007/s11914-025-00910-9","pmid":"40192921","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11985","title":"Liraglutide-Induced Liver Injury: A Case Report and Review.","authors":"Lai, Mark; Hosking, Patrick; Sawhney, Rohit; Nicoll, Amanda","year":2025,"journal":"Case reports in gastroenterology, 19(1), 653-658","doi":"10.1159/000547634","pmid":"41064547","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11986","title":"Semaglutide and High-Intensity Interval Exercise Attenuate Cognitive Impairment in Type 2 Diabetic Mice via BDNF Modulation.","authors":"Lai, Sijie; Kang, Zhenghong; Sun, Jianting; Wang, Ziyu; Xu, Yanzi; Xing, Sisi; Feng, Mengying; Wang, Yiyi; Liu, Hua","year":2025,"journal":"Brain sciences, 15(5)","doi":"10.3390/brainsci15050480","pmid":"40426650","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11987","title":"Association of Glucagon-Like Peptide-1 Receptor Agonists With Optic Nerve and Retinal Adverse Events: A Population-Based Observational Study Across 180 Countries.","authors":"Lakhani, Moiz; Kwan, Angela T H; Mihalache, Andrew; Popovic, Marko M; Nanji, Keean; Xie, Jim S; Feo, Alessandro; Rabinovitch, David; Shor, Reut; Sadda, SriniVas; Sarraf, David; Hurley, Bernard; Margolin, Edward A; Kertes, Peter J; Chaudhary, Varun; Muni, Rajeev H","year":2025,"journal":"American journal of ophthalmology, 277, 148-168","doi":"10.1016/j.ajo.2025.05.007","pmid":"40383360","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11988","title":"An overview of oxytocin integrative mechanisms in autism spectrum disorder.","authors":"Lal, Nand; Song, Bin; Zhang, Chi; Al-Shehari, Wadee Abdullah; Jabeen, Sadia; Ahmed, Niaz; Edrees, Wadhah Hassan; Gupta, Radheshyam; Soomro, Samiullah; Cui, Feiyun; Qasem, Eglal Ahmed","year":2025,"journal":"Discover mental health, 5(1), 185","doi":"10.1007/s44192-025-00331-1","pmid":"41288818","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11989","title":"Real-World Prescribing of Renal and Cardiovascular Protective Drugs in Patients With Type 2 Diabetes and Chronic Kidney Disease: Analysis of Data From a Western Australian Quaternary Hospital.","authors":"Lan, Nick S R; McFadden, Ben; Johnson, Andrew; Shedden, Phillip; Fegan, P Gerry; Puttagunta, Harish; Ho, Sharon; Gillett, Richard; Swaminathan, Ramyasuda; Dwivedi, Girish","year":2025,"journal":"Heart, lung & circulation, 34(10), 1089-1097","doi":"10.1016/j.hlc.2025.07.007","pmid":"40912924","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 2,216 patients with type 2 diabetes and chronic kidney disease discharged from an Australian hospital (2020–2024), only 21.3% were prescribed an SGLT2 inhibitor and 7.4% a GLP-1 agonist — despite strong evidence these drugs improve renal and cardiovascular outcomes. Only 3.6% received semaglutide specifically, and a mere 0.1% received finerenone. One-third (33.2%) of patients were discharged on none of the four recommended protective drug classes. Encouragingly, prescribing trends improved over the study period: SGLT2 inhibitor prescriptions rose from 7.9% to 38.7% (P<0.001) and GLP-1 agonist prescriptions from 6.3% to 11.7% (P=0.007).","whyItMatters":"Major clinical trials have established that SGLT2 inhibitors, GLP-1 agonists like semaglutide, and finerenone protect the kidneys and heart in patients with type 2 diabetes and CKD. Yet this real-world data reveals a massive gap between evidence and practice: most patients leave the hospital without these proven treatments. Identifying and addressing barriers to prescribing could significantly reduce kidney failure and cardiovascular events in this high-risk population.","specificNumbers":"n=2,216 · Mean age 78.2 years · ACEi/ARB: 56.1% · SGLT2i: 21.3% · GLP-1 agonist: 7.4% · Semaglutide: 3.6% · Finerenone: 0.1% · None of 4 classes: 33.2% · SGLT2i trend: 7.9%→38.7% · GLP-1 trend: 6.3%→11.7%","methodology":"Retrospective cohort study of the ReDiCare project. Identified patients with T2D and CKD admitted to a quaternary hospital in Western Australia between January 2020 and September 2024 using ICD-10-AM codes and eGFR data. CKD was defined as eGFR <60 mL/min/1.73m² for >3 months. Discharge medications were analyzed for prescribing of SGLT2 inhibitors, GLP-1 agonists, finerenone, and ACE inhibitors/ARBs. Time trends in prescribing were assessed across the study period.","limitations":"Single-center study at one Australian hospital, limiting generalizability. Retrospective design relying on discharge prescription data — actual medication adherence not assessed. The elderly population (mean age 78.2) may have more contraindications or provider caution with newer agents. Reasons for non-prescribing (contraindications, cost, patient preference) were not captured."},{"rthcId":"RPEP-11990","title":"Employing an Artificial Intelligence Platform to Enhance Treatment Responses to GLP-1 Agonists by Utilizing Metabolic Variability Signatures Based on the Constrained Disorder Principle.","authors":"Landau, Jakob; Tiram, Yariv; Ilan, Yaron","year":2025,"journal":"Biomedicines, 13(11)","doi":"10.3390/biomedicines13112645","pmid":"41301738","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Metabolic variability signatures — natural fluctuations in heart rate, blood pressure, lipid levels, glucose, and body weight — can predict treatment responses and health outcomes. Increased variability in most metabolic parameters predicts worse outcomes. The Constrained Disorder Principle (CDP) describes how biological systems function within optimal variability ranges. AI platforms based on CDP can leverage rather than suppress this variability to enhance therapeutic outcomes, and this approach could be applied to personalize GLP-1 receptor agonist therapy for metabolic disorders.","whyItMatters":"GLP-1 drugs like semaglutide work differently for different people, and predicting who will respond well has been challenging. This review proposes using AI to analyze patients' natural metabolic variability patterns to personalize GLP-1 therapy. Instead of treating metabolic fluctuations as noise, the CDP framework uses them as actionable data. This could help overcome drug resistance and improve outcomes for patients on GLP-1 agonists.","specificNumbers":"Review of metabolic variability across heart rate, blood pressure, lipids, glucose, body weight, and metabolic rate · CDP-based AI applied to heart failure, cancer, multiple sclerosis · genetic polymorphisms influence GLP-1 RA responses","methodology":"This is a comprehensive literature review examining metabolic variability across multiple health parameters, its relationship to treatment responses (particularly GLP-1 receptor agonist therapy), and the application of CDP-based AI systems. The review synthesizes evidence from cardiovascular, metabolic, and neurodegenerative disease studies.","limitations":"This is a theoretical/review paper proposing a framework rather than presenting direct clinical evidence for AI-personalized GLP-1 therapy. The CDP-based AI platform's effectiveness has been demonstrated in other conditions but not yet specifically validated for optimizing GLP-1 agonist treatment. The concept of leveraging metabolic variability for treatment personalization remains largely theoretical."},{"rthcId":"RPEP-11991","title":"Glaucoma Risk Reduction as a Secondary Benefit of Glucagon-like Peptide-1 Receptor Agonists: A Review of Emerging Evidence.","authors":"Lang, Mary V; Vasu, Pranav; Dorairaj, Emily A; Bhartiya, Shibal; Dorairaj, Syril K","year":2025,"journal":"Journal of current glaucoma practice, 19(4), 223-228","doi":"10.5005/jp-journals-10078-1501","pmid":"41523168","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11992","title":"The Effect of a Low-Energy and Low-Glycemic Diet on Adipose Tissue Metabolism and Energy Expenditure in Women with Excess Body Weight.","authors":"Lange, Ewa; Pałkowska-Goździk, Ewelina","year":2025,"journal":"Nutrients, 17(23)","doi":"10.3390/nu17233789","pmid":"41374079","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11993","title":"Interplay of neuropeptide Y and autophagy in Alzheimer's disease: Therapeutic perspectives and mechanistic insights.","authors":"Lanjewar, Dhiraj; Katariya, Raj; Kale, Vinita; Taksande, Brijesh; Umekar, Milind; Vinchurney, Madhura","year":2025,"journal":"Neuropeptides, 113, 102547","doi":"10.1016/j.npep.2025.102547","pmid":"40695083","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11994","title":"Neurons Co-Expressing GLP-1, CCK, and PYY Receptors Particularly in Right Nodose Ganglion and Innervating Entire GI Tract in Mice.","authors":"Lansbury, Elizabeth Laura; Vana, Vasiliki; Lund, Mari Lilith; Ludwig, Mette Q; Mamedova, Esmira; Gautron, Laurent; Arnold, Myrtha; Egerod, Kristoffer Lihme; Kuhre, Rune Ehrenreich; Holst, Jens Juul; Rekling, Jens; Schwartz, Thue W; Pankratova, Stanislava; Dmytriyeva, Oksana","year":2025,"journal":"International journal of molecular sciences, 26(5)","doi":"10.3390/ijms26052053","pmid":"40076675","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Using RNAscope combined with immunohistochemistry, the researchers found that most GLP-1 receptor (GLP1R), cholecystokinin A receptor (CCKAR), and neuropeptide Y2 receptor (NPY2R) neurons in the nodose ganglia co-expressed all three receptors. These triple-positive neurons were preferentially located in the right nodose ganglion.\n\nDual retrograde labeling with distinct tracers confirmed that neurons co-expressing GLP1R, CCKAR, and NPY2R innervated both the stomach and the distal colon — meaning individual nerve cells sample chemical signals from the entire gastrointestinal tract. Additional receptor subtypes (NTSR1, GPR65, 5-HT3A) showed different distribution patterns, with NTSR1 and GPR65 neurons nearly always co-expressing both receptors.","whyItMatters":"GLP-1 drugs like semaglutide work partly through vagal nerve signaling, but exactly how the brain receives and integrates gut hormone signals has been unclear. This study shows that individual nerve cells can simultaneously detect multiple satiety hormones from different parts of the digestive tract. Understanding this integration could explain why combination gut hormone therapies (targeting GLP-1, CCK, or PYY together) may produce stronger appetite suppression than single-target drugs.","specificNumbers":"","methodology":"The study used mice (C57BL/6 strain) and combined RNAscope in situ hybridization with immunohistochemistry to map receptor expression in nodose ganglion neurons. Retrograde labeling with two distinct fluorescent tracers injected into different parts of the GI tract identified which neurons innervated which organs. This allowed the researchers to determine both receptor co-expression patterns and the anatomical reach of individual neurons.","limitations":"This study was conducted entirely in mice, so the receptor co-expression patterns may not be identical in humans. The research mapped receptor expression but did not test functional responses — having a receptor present doesn't guarantee it's actively signaling. The study also could not determine whether these triple-receptor neurons change their expression patterns in obesity or after bariatric surgery."},{"rthcId":"RPEP-11995","title":"Pharmacologic Management of Obesity in Neuro-Oncology: A Case Report.","authors":"Lardieri, Alexandra; Thaker, Vidhu; Citron-Zafrin, Kate; Garvin, James H; Zacharoulis, Stergios; Ladas, Elena J","year":2025,"journal":"Case reports in oncology, 18(1), 169-173","doi":"10.1159/000543178","pmid":"39980512","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11996","title":"GPCRVS - AI-driven Decision Support System for GPCR Virtual Screening.","authors":"Latek, Dorota; Prajapati, Khushil; Dragan, Paulina; Merski, Matthew; Osial, Przemysław","year":2025,"journal":"International journal of molecular sciences, 26(5)","doi":"10.3390/ijms26052160","pmid":"40076783","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11997","title":"In silico prediction of optimal multifactorial intervention in chronic kidney disease.","authors":"Latosinska, Agnieszka; Mina, Ioanna K; Nguyen, Thi Minh Nghia; Golovko, Igor; Keller, Felix; Mayer, Gert; Rossing, Peter; Staessen, Jan A; Delles, Christian; Beige, Joachim; Glorieux, Griet; Clark, Andrew L; Schanstra, Joost P; Vlahou, Antonia; Peter, Karlheinz; Rychlík, Ivan; Ortiz, Alberto; Campbell, Archie; Rupprecht, Harald; Persson, Frederik; Mischak, Harald; Siwy, Justyna","year":2025,"journal":"Journal of translational medicine, 23(1), 943","doi":"10.1186/s12967-025-06977-3","pmid":"40842026","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 935 CKD patients with validated kidney event outcomes:\n\n- CKD273 peptide classifier confirmed as predictor of major adverse kidney events (≥40% eGFR decline or kidney failure)\n- In silico simulation of 6 interventions: mineralocorticoid receptor antagonist, SGLT2 inhibitor, GLP-1 receptor agonist, ARB, olive oil diet, and exercise\n- Simulated optimal interventions reduced median CKD273 from 0.57 to 0.039 (P < 0.0001)\n- The combination of all available treatments was NOT the most frequently predicted optimal intervention — personalization mattered\n- Patients with higher baseline scores required more complex combinations\n- Approach uses individual urinary peptide profiles + known treatment effects on peptide abundance","whyItMatters":"This study demonstrates that urinary peptide patterns can guide personalized treatment selection — a major advance toward precision medicine in kidney disease. Rather than giving all patients the same drugs, the peptide profile identifies which combination would work best for each individual. If validated prospectively, this could transform how kidney disease is treated.","specificNumbers":"","methodology":"Retrospective cohort of 935 CKD patients with urinary peptidomic data. CKD273 classifier scores were validated against major adverse kidney events over median 1.5-year follow-up. In silico treatment simulation used: (1) individual baseline urinary peptide profiles, and (2) previously defined fold changes in peptide abundance from clinical trials of four drugs, dietary intervention, and exercise. Simulated CKD273 scores were recalibrated against trial outcomes. Optimal single and combination treatments were predicted for each patient.","limitations":"The treatment simulations are based on average drug effects from prior trials, which may not perfectly predict individual responses. The study is retrospective and computational — the in silico predictions need prospective clinical validation. The model assumes treatment effects on peptides are additive, which may not always be true. A prospective validation trial is planned but not yet completed."},{"rthcId":"RPEP-11998","title":"Factors Associated With Initiation of Sodium-Glucose Cotransporter 2 Inhibitor and Glucagon-Like Peptide 1 Receptor Agonists in Patients With Diabetes and Kidney Disease: A Post Hoc Analysis of the Kidney CHAMP Trial.","authors":"Lavenburg, Linda-Marie U; Mosslemi, Mitra; Han, Zhuoheng; Weltman, Melanie R; Alghwiri, Alaa; Fischer, Gary; Rollman, Bruce L; Yabes, Jonathan G; Jhamb, Manisha","year":2025,"journal":"Diabetes spectrum : a publication of the American Diabetes Association, 38(4), 512-524","doi":"10.2337/ds25-0046","pmid":"41257235","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-11999","title":"Pediatric reference values for glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon in children and adolescents.","authors":"Lawaetz, Trine Witzner Hessel; Dalgas-Madsen, Amalie; Mørk, Freja Cecilie Barrett; Jensen, Andreas Kryger; Jensen, Verena Hirschberg; Pociot, Flemming; Heidemann, Malene Søborg; Shou, Anders Jørgen; Wedderkopp, Niels; Johannesen, Jesper","year":2025,"journal":"Pediatric research","doi":"10.1038/s41390-025-04551-7","pmid":"41436635","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12000","title":"Feasibility and Safety of Peptide Receptor Radionuclide Therapy With 177 Lu-DOTATATE for Neuroendocrine Tumor in a Patient With Sickle Cell Anemia.","authors":"Lawal, Ismaheel O; Gbolahan, Olumide B; Marcus, Charles; Jones, Aaron T; Shaib, Walid L; Muzahir, Saima","year":2025,"journal":"Clinical nuclear medicine, 50(11), e661-e664","doi":"10.1097/RLU.0000000000005790","pmid":"40029803","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The patient successfully completed 4 cycles of PRRT with 177Lu-DOTATATE despite having sickle cell anemia, a condition that could potentially complicate this type of therapy. Renal, hematologic, and liver lab values remained stable throughout treatment. Post-treatment, the disease remained stable for up to 13 months, and serum chromogranin A levels — a key tumor marker for neuroendocrine tumors — declined by 45%.\n\nThis is the first reported case demonstrating that PRRT can be safely administered to patients with sickle cell anemia, a population typically excluded from clinical trials due to concerns about hematologic complications.","whyItMatters":"Patients with sickle cell anemia are often excluded from treatments like PRRT due to concerns about worsening blood-related side effects. This case provides the first evidence that such patients can safely receive this peptide-based targeted radiation therapy, potentially opening up an important treatment option for an underserved patient population with neuroendocrine tumors.","specificNumbers":"","methodology":"This was a single-patient case report. A 56-year-old woman with sickle cell anemia and metastatic neuroendocrine tumor that was refractory to somatostatin analog therapy received 4 cycles of PRRT with 177Lu-DOTATATE. Researchers monitored her renal function, hematologic parameters, liver labs, disease status, and serum chromogranin levels throughout and after treatment.","limitations":"As a single case report, the findings cannot be generalized to all patients with sickle cell anemia. There was no comparison group, and the treatment schedule was disrupted by hospitalizations, making it difficult to assess whether the delays affected efficacy. Long-term outcomes beyond 13 months were not reported."},{"rthcId":"RPEP-12001","title":"Subgroup analysis by sex and baseline BMI in people with a BMI ≥27 kg/m2 in the phase 2 trial of survodutide, a glucagon/GLP-1 receptor dual agonist.","authors":"le Roux, Carel W; Steen, Oren; Lucas, Kathryn J; Startseva, Elena; Unseld, Anna; Hussain, Samina Ajaz; Hennige, Anita M","year":2025,"journal":"Diabetes, obesity & metabolism, 27(4), 1773-1782","doi":"10.1111/dom.16167","pmid":"39821928","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12002","title":"GLP-1 receptor agonist indications and prescriptions among adults who do and do not smoke.","authors":"Leavens, Eleanor L S; Arnold, Michael J; Nollen, Nicole L; Sanderson Cox, Lisa; Brown, Kristy A; Ellerbeck, Edward F","year":2025,"journal":"medRxiv : the preprint server for health sciences","doi":"10.1101/2025.08.12.25331941","pmid":"40832400","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12003","title":"GABAergic signaling by VIP interneurons gates running-dependent visual recovery in the adult brain.","authors":"Lebedeva, Anna; Kling, Friedrich; Rakela, Benjamin; Stryker, Michael P; Sun, Jennifer Y","year":2025,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2025.05.21.655402","pmid":"40475408","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Using two-photon calcium imaging in awake adult mice, researchers found that monocular deprivation produced comparable ocular dominance shifts regardless of whether VIP peptide or GABA signaling was disrupted. However, disrupting GABA signaling from VIP interneurons specifically impaired the recovery of binocular responses after the deprived eye was reopened. Running enhanced contralateral eye responses in visual cortex, but this eye-specific modulation was altered during recovery and depended on VIP signaling pathways.","whyItMatters":"Adult brain plasticity is much more limited than in children, making visual recovery from conditions like amblyopia (lazy eye) difficult. Understanding that GABA from VIP interneurons specifically gates visual restoration could lead to targeted therapies that reopen windows of plasticity in the adult visual system — potentially helping adults recover from vision disorders.","specificNumbers":"","methodology":"Two-photon calcium imaging was performed in awake adult mice during monocular deprivation and subsequent binocular recovery. Genetic tools were used to selectively disrupt either VIP peptide or GABA release from VIP interneurons. Visual responses were measured during both stationary and running conditions to dissect locomotion-dependent effects.","limitations":"This is a mouse study using genetic manipulations, so findings may not directly translate to human visual recovery. The monocular deprivation model is a simplified version of human amblyopia. The study used a preprint server (bioRxiv) and may not yet be peer-reviewed. The specific interaction between running and VIP/GABA pathways requires further mechanistic investigation."},{"rthcId":"RPEP-12004","title":"In vitro and in vivo efficacy of the Active Oligo Skin complex™, a new active ingredient processed from seawater, on multiple parameters of atopic skin.","authors":"Lebonvallet, Nicolas; Catovic, Chloé; Feuilloley, Marc; Leschiera, Raphael; Reux, Alexia; Talagas, Matthieu; Cousin, Ianis; Misery, Laurent; Simon, Emilie; Chopin, Sylvie; Gardères, Johan","year":2025,"journal":"Skin health and disease, 5(1), 22-30","doi":"10.1093/skinhd/vzae029","pmid":"40125013","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12005","title":"Incretin Receptor Agonist, Semaglutide, as a Treatment for Alectinib-Induced Excessive Weight Gain. A Case Report.","authors":"Lee, Alexandria T M; Park, Cathleen June; Arter, Zhaohui Liao; Nagasaka, Misako; Ou, Sai-Hong Ignatius","year":2025,"journal":"Lung Cancer (Auckland, N.Z.), 16, 199-203","doi":"10.2147/LCTT.S549011","pmid":"41477303","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12006","title":"Multilevel Screening Platform Utilizing Cellular and Zebrafish Models to Identify Short Peptides with High Improvement of Motor Neuron Growth.","authors":"Lee, Bing-Chang; Wang, Chun-Cheng; Chen, Shan-Pin; Tsai, Huai-Jen","year":2025,"journal":"International journal of molecular sciences, 27(1)","doi":"10.3390/ijms27010281","pmid":"41516158","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12007","title":"Efficacy and safety in tirzepatide-treated Korean adults with type 2 diabetes-A post hoc analysis of SURPASS-AP-combo and SURPASS-3.","authors":"Lee, Byung Wan; Lee, Chang Beom; Lim, Soo; Kim, Sin Gon; Kim, Nan Hee; Won, Jong Chul; Lee, Woo Je; Kang, Min Ju; Yuh, Ju Young; Du, Li Ying; Lim, Hyojin; Ahn, Kyu Jeung","year":2025,"journal":"Diabetes, obesity & metabolism, 27(12), 7110-7122","doi":"10.1111/dom.70111","pmid":"40954943","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12008","title":"Postbiotic Potential of Heat-Killed Lacticaseibacillus paracasei HP7 in Functional Dyspepsia.","authors":"Lee, Daehyeop; Jeong, Ji-Woong; Kim, Joo-Yun; Shim, Jae-Jung; Lee, Jae-Hwan","year":2025,"journal":"Journal of microbiology and biotechnology, 35, e2508029","doi":"10.4014/jmb.2508.08029","pmid":"41162162","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12009","title":"Injectable glycol chitosan hydrogel system for sustained drug delivery to treat neuropathic pain.","authors":"Lee, Daye; Han, Gong Ho; Kim, Seong Jun; Ko, Wan-Kyu; Kim, Min Je; Ju, Gi-Beom; Sheen, Seung Hun; Hong, Je Beom; Cho, Min Jai; Sohn, Seil","year":2025,"journal":"International journal of biological macromolecules, 333(Pt 1), 148757","doi":"10.1016/j.ijbiomac.2025.148757","pmid":"41205944","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The CHA-DEX-MEPI hydrogel demonstrated sustained release of both dexamethasone and mepivacaine for more than 72 hours, compared to rapid clearance with standard solution injections.\n\nIn activated macrophages, the hydrogel prolonged reduction of inflammatory cytokine gene expression for three days compared to a simple drug solution.\n\nIn rats with chronic constriction nerve injury, the hydrogel significantly reduced both cold and mechanical allodynia (pain from normally non-painful stimuli) beginning seven days post-injury. At 14 days post-injury, the hydrogel produced sustained reductions in key nociceptive markers including TRPV1, TRPA1, and importantly CGRP — a neuropeptide directly involved in pain transmission and neurogenic inflammation.","whyItMatters":"Chronic neuropathic pain affects millions of people and is notoriously difficult to treat. Current epidural injections provide temporary relief but require frequent repeat procedures and can cause side effects from uncontrolled drug spread. A hydrogel that keeps medications exactly where they're needed and releases them slowly could extend pain relief from hours to weeks, potentially reducing the number of procedures needed and improving quality of life for chronic pain patients.","specificNumbers":"","methodology":"The hydrogel was synthesized by combining glycolic chitosan and oxidized hyaluronic acid, which self-crosslink to form an injectable gel. Dexamethasone and mepivacaine were embedded within the gel matrix. In vitro testing used bone marrow-derived macrophages activated with LPS to assess anti-inflammatory duration. In vivo testing used the chronic constriction injury (CCI) model in Sprague-Dawley rats, with pain responses measured over 14 days using cold and mechanical allodynia tests. Nociceptive marker expression (TRPV1, TRPA1, CGRP) was assessed at 14 days post-injury.","limitations":"This is an animal study using a surgically induced nerve injury model, which may not fully represent the diverse causes of neuropathic pain in humans. The 14-day follow-up is relatively short for a chronic pain condition. Specific drug concentrations in the hydrogel and exact release kinetics are not fully detailed in the abstract. The sample size per group is not specified. Safety and biocompatibility data beyond the 14-day period are not reported. Translation to human epidural use would require extensive safety testing."},{"rthcId":"RPEP-12010","title":"Therapeutic Efficacy of Neoadjuvant Peptide Receptor Radionuclide Therapy in Neuroendocrine Tumors: A Meta-analysis.","authors":"Lee, Dong Yun; Kim, Yong-Il","year":2025,"journal":"Clinical nuclear medicine","doi":"10.1097/RLU.0000000000006276","pmid":"41474781","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12011","title":"Safety of Intravenous Infusion of BPC157 in Humans: A Pilot Study.","authors":"Lee, Edwin; Burgess, Kailynd","year":2025,"journal":"Alternative therapies in health and medicine, 31(5), 20-24","doi":null,"pmid":"40131143","tags":["bpc-157","safety"],"studyType":"pilot-study","evidenceStrength":"preliminary","keyFinding":"Intravenous BPC-157 at doses of 10 mg and 20 mg was well-tolerated in two healthy adults with no adverse effects. Blood work monitoring showed no measurable effects on heart, liver, kidney, thyroid, or blood glucose biomarkers across the three-day study period.\n\nThis is the first published study examining intravenous BPC-157 administration in humans. Both participants had previously received IV BPC-157, and the IRB-approved protocol used escalating doses over two consecutive days.","whyItMatters":"BPC-157 is one of the most widely discussed peptides in the wellness and biohacking community, yet virtually all published research has been in animals. The near-complete absence of human data has been the elephant in the room. This tiny pilot study from Dr. Edwin Lee — one of very few researchers publishing human BPC-157 data — provides the first formal safety assessment of intravenous administration. While far too small to be definitive, it's a step toward filling the massive evidence gap between animal studies and widespread human use.","specificNumbers":"n=2 · 10 mg IV on day 1 · 20 mg IV on day 2 · 250 cc normal saline · 1-hour infusions · 0 adverse effects reported · no changes in heart, liver, kidney, thyroid, or glucose markers","methodology":"IRB-approved pilot safety study. Two participants had baseline blood work and vital signs recorded, then received 10 mg BPC-157 in 250 cc saline IV over one hour on day 1, followed by 20 mg on day 2. Fasting blood work and vitals were repeated on days 2 and 3. Participants were questioned about side effects at each visit.","limitations":"Extremely small sample (n=2) — essentially an anecdotal safety observation, not a powered study. Both participants had prior IV BPC-157 exposure, so truly naïve reactions weren't captured. Only three days of monitoring — no long-term safety data. Published in an alternative medicine journal, not a high-impact clinical journal. No control group. The doses used may not reflect typical clinical applications."},{"rthcId":"RPEP-12012","title":"Skin Anti-Aging and Moisturizing Effects of Low-Molecular-Weight Collagen Peptide Supplementation in Healthy Adults: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.","authors":"Lee, Eunkyoung; Ahn, Dong Kyu; Kim, Jong Hoon; Lee, Sunghee; Kim, Han Jo; Lee, Hae Kwang; Shin, Jin Hee","year":2025,"journal":"Journal of microbiology and biotechnology, 35, e2507008","doi":"10.4014/jmb.2507.07008","pmid":"40935395","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12013","title":"D-Allulose Regulates Obesity via Endoplasmic Reticulum Stress-Mediated Glucagon-Like Peptide-1 Receptor Pathway.","authors":"Lee, Geum-Hwa; Lee, Hwa-Young; Lim, Young Jae; Kim, Ji-Hyun; Rah, So-Young; Chung, Myung Ja; Park, Se Young; Sa, Soonok; Lee, Hyewon; Soh, Yunjo; Kim, Junghyun; Chae, Han-Jung","year":2025,"journal":"Antioxidants & redox signaling, 43(16-18), 819-832","doi":"10.1177/15230864251399183","pmid":"41327798","tags":[],"studyType":"animal study","evidenceStrength":"low","keyFinding":"D-allulose, a rare low-calorie sugar, reduced obesity in mice fed a high-fat diet by stabilizing the GLP-1 receptor through a specific molecular mechanism. The sugar works by inhibiting a stress-response pathway (the IRE1α-RIDD axis) in cells that would otherwise degrade the GLP-1 receptor. Crucially, the anti-obesity effects disappeared completely in mice genetically lacking the GLP-1 receptor, proving that D-allulose's weight-regulating benefits depend entirely on a functioning GLP-1 receptor. The study also identified the GLP-1 receptor as a previously unknown target of the RIDD decay pathway.","whyItMatters":"GLP-1 receptor agonist drugs (like semaglutide and tirzepatide) are transforming obesity treatment, but they're expensive and require injections. If a common sugar substitute like D-allulose can stabilize and enhance the GLP-1 receptor's function through a different mechanism — by preventing its degradation rather than directly activating it — this could offer a complementary or more accessible approach to leveraging the GLP-1 pathway for weight management.","specificNumbers":"12-week study · High-fat diet model · Anti-obesity effects abolished in GLP-1R knockout mice · GLP-1R identified as novel RIDD target","methodology":"Researchers conducted in vitro studies examining how D-allulose affects adipocyte (fat cell) differentiation through the NADP+/NADPH-ROS-IRE1α-RIDD signaling axis. They then performed 12-week in vivo studies comparing D-allulose administration in high-fat diet-fed wild-type mice versus GLP-1 receptor knockout mice, measuring body weight and obesity-related parameters.","limitations":"This is a mouse study with no human data. The doses of D-allulose used in mice may not translate directly to human consumption levels. The 12-week duration, while substantial for mice, doesn't address long-term effects. The mechanism is complex and involves multiple signaling steps, any of which might differ in humans. The GLP-1R knockout model, while proving dependence on the receptor, represents a complete absence that doesn't reflect natural variation in GLP-1R expression."},{"rthcId":"RPEP-12014","title":"Enhancing the bystander effect of antibody-drug conjugate by using a novel caspase-3 cleavable peptide linker to overcome tumor heterogeneity.","authors":"Lee, Ha Kyeong; Kim, Byoungmo; Ko, Yoon Gun; Chung, Seung Woo; Shim, Wan Seob; Choi, So-Young; Lee, Se-Ra; Kim, Sang Yoon; Byun, Youngro","year":2025,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 382, 113738","doi":"10.1016/j.jconrel.2025.113738","pmid":"40246243","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12015","title":"Subjective Olfactory Impairment in a Patient Undergoing Anti-Obesity Pharmacotherapy: A Case of Symptom-Test Discrepancy.","authors":"Lee, Hye Jun; Min, Hyun Jin","year":2025,"journal":"Life (Basel, Switzerland), 15(9)","doi":"10.3390/life15091349","pmid":"41010291","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12016","title":"Cell-Penetrating Peptide Like Anti-Programmed Cell Death-Ligand 1 Peptide Conjugate-Based Self-Assembled Nanoparticles for Immunogenic Photodynamic Therapy.","authors":"Lee, Jun-Hyuck; Yang, Seong-Bin; Park, Seong Jin; Kweon, Seho; Ma, Gaeun; Seo, Minho; Kim, Ha Rin; Kang, Tae-Bong; Lim, Ji-Hong; Park, Jooho","year":2025,"journal":"ACS nano, 19(2), 2870-2889","doi":"10.1021/acsnano.4c16128","pmid":"39761412","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12017","title":"Enhancement of Structural Stability and IgG Affinity of a Z34C-Derived α-Helical Peptide via Lactam Stapling.","authors":"Lee, Jung Gu; Lee, Inseo; Kim, Joo-Young; Kim, Suin; Jeong, Woo-Jin; Kim, Ji-Eun","year":2025,"journal":"Antibodies (Basel, Switzerland), 14(4)","doi":"10.3390/antib14040108","pmid":"41440497","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Two peptides (SpA h1 and SpA h2) were designed based on the Fc-binding helices of the Z34C domain from Protein A. Lactam stapling — introducing a chemical bridge between lysine and glutamic acid residues at positions i and i+4 — significantly increased their alpha-helical content as measured by circular dichroism spectroscopy.\n\nThe stapled peptides showed markedly improved IgG-binding performance in fluorescence-based capture assays. Surface plasmon resonance confirmed specific, concentration-dependent Fc binding. Critically, (s)SpA h1 demonstrated enhanced resistance to α-chymotrypsin digestion compared to its linear counterpart and showed strong Fc selectivity with minimal Fab binding — properties essential for practical antibody purification and bioconjugation applications.","whyItMatters":"Antibody-based drugs (biologics) are among the fastest-growing sectors of the pharmaceutical industry, and antibody purification using Protein A chromatography is a bottleneck in manufacturing. Protein A is expensive, large, and can leach into the final product. Small, chemically defined peptides that match its binding ability could reduce costs, improve purity, and enable novel bioconjugation strategies. Lactam stapling addresses the main weakness of short peptides — their tendency to unfold and get degraded — making them practical candidates for industrial and diagnostic use.","specificNumbers":"","methodology":"The researchers designed two peptide sequences from the Fc-binding helices of the Z34C domain of Staphylococcus aureus Protein A. Lactam staples were introduced by placing lysine and glutamic acid at i, i+4 positions to form intramolecular bridges. Structural characterization used circular dichroism (CD) spectroscopy. Binding was assessed via fluorescence-based IgG capture assays and surface plasmon resonance (SPR). Enzymatic stability was tested using α-chymotrypsin proteolysis assays. Fc versus Fab selectivity was also evaluated.","limitations":"The study is at the design and characterization stage — the peptides have not been tested on actual chromatography columns for antibody purification under industrial conditions. Binding affinity values from SPR were not quantified with KD values in the abstract. Only human IgG was tested; performance with other species' antibodies is unknown. Long-term stability under harsh elution conditions (low pH) used in industrial purification was not assessed. Cost and scalability of peptide synthesis with lactam stapling were not addressed."},{"rthcId":"RPEP-12018","title":"Alpha-defensins increase NTHi binding but not engulfment by the macrophages enhancing airway inflammation in Alpha-1 antitrypsin deficiency.","authors":"Lee, Jungnam; Mohammad, Naweed; Han, Kyudong; Flagg-Dowie, Tammy; Magallon, Maria; Brantly, Mark L; Serban, Karina A","year":2025,"journal":"Frontiers in immunology, 16, 1543729","doi":"10.3389/fimmu.2025.1543729","pmid":"40013145","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12019","title":"Preparation and Therapeutic Evaluation of Engineered Semaglutide and Statin-Lipid Conjugate-Based Nanoparticle.","authors":"Lee, Kyeong-Ju; Yang, Seong-Bin; Lee, Jae-Hyeon; Seo, Bison; Won, Hyung-Sik; Park, Jooho","year":2025,"journal":"Pharmaceutics, 17(4)","doi":"10.3390/pharmaceutics17040480","pmid":"40284475","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12020","title":"Directed Evolution of AtMP2 Peptide: Unlocking Enhanced Antibacterial Potential from Anabas testudineus.","authors":"Lee, Li Ting; Ang, Arnold; Najm, Ahmed; Adnan, Adura Mohd; Nordin, Akram Mohd; Mahmood, Ibrahim; Dunkhorol, Sarantuya; Fazry, Shazrul; Law, Douglas","year":2025,"journal":"Molecules (Basel, Switzerland), 30(23)","doi":"10.3390/molecules30234590","pmid":"41375186","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Two engineered variants of the AtMP2 peptide (AtMP2-1 and AtMP2-2), generated through systematic directed evolution, demonstrated higher antimicrobial activity against Gram-positive bacteria than the parent AtMP2 peptide, as measured by Minimum Inhibitory Concentration (MIC) and Kirby-Bauer disk diffusion assays. Activity against Gram-negative bacteria was comparatively lower.\n\nCytotoxicity testing using SRB assays on HS-27 (human fibroblast) and Vero cell lines showed both variants were safe at 20 µg/mL. Molecular docking analysis revealed strong binding interactions with bacterial proteins involved in cell death pathways, including SecA, RpoB, GyrA, ClpP, and MetG, with more negative scores indicating stronger binding.","whyItMatters":"Antimicrobial resistance is a global health crisis, and antimicrobial peptides (AMPs) represent one of the most promising alternatives to conventional antibiotics. Fish-derived AMPs are particularly interesting because fish constantly live in bacteria-rich aquatic environments and have evolved potent natural defenses. Showing that directed evolution can enhance these natural peptides' antibacterial potency while maintaining safety opens a pathway toward developing new anti-infective agents.","specificNumbers":"","methodology":"Researchers extracted antimicrobial peptides from the epidermal mucus of climbing perch (Anabas testudineus). The AtMP2 peptide was selected and subjected to systematic directed evolution to generate variants. Characterization was performed using computational tools (APD3, CAMP, AMPFun). Two promising variants (AtMP2-1 and AtMP2-2) were synthesized and tested for antibacterial activity via MIC determination and Kirby-Bauer disk diffusion against Gram-positive and Gram-negative bacteria. Cytotoxicity was assessed using SRB assays on HS-27 and Vero cell lines. Molecular docking (ZDOCK and HPEPDOCK) evaluated binding to bacterial target proteins.","limitations":"This is an in vitro study — no animal infection models were used to test efficacy in a living system. The enhanced activity was mainly against Gram-positive bacteria, with limited improvement against Gram-negative organisms (which are often the more challenging clinical targets). Specific MIC values were not provided in the abstract. The molecular docking results are computational predictions that require experimental validation. Stability, pharmacokinetics, and in vivo toxicity remain untested."},{"rthcId":"RPEP-12021","title":"Cardiovascular and Kidney Outcomes and Mortality With Long-Acting Injectable and Oral Glucagon-Like Peptide 1 Receptor Agonists in Individuals With Type 2 Diabetes: A Systematic Review and Meta-analysis of Randomized Trials.","authors":"Lee, Matthew M Y; Sattar, Naveed; Pop-Busui, Rodica; Deanfield, John; Emerson, Scott S; Inzucchi, Silvio E; Mann, Johannes F E; Marx, Nikolaus; Mulvagh, Sharon L; Poulter, Neil R; Badve, Sunil V; Pratley, Richard E; Perkovic, Vlado; Buse, John B; McGuire, Darren K","year":2025,"journal":"Diabetes care, 48(5), 846-859","doi":"10.2337/dc25-0241","pmid":"40156846","tags":[],"studyType":"meta-analysis","evidenceStrength":"high","keyFinding":"Long-acting GLP-1 receptor agonists — both injectable and oral forms — significantly reduced cardiovascular events, heart failure hospitalizations, kidney complications, and death in people with type 2 diabetes. Across 10 randomized trials with over 71,000 participants, GLP-1 RAs reduced major adverse cardiovascular events by 14% (HR 0.86), heart failure hospitalization by 14%, composite kidney outcomes by 17%, and all-cause mortality by 12%.\n\nCritically, there was no significant difference in benefits between subcutaneous (injectable) and oral formulations, and no increased risks of severe hypoglycemia, retinopathy, or pancreatic events were found.","whyItMatters":"This is the most comprehensive meta-analysis of GLP-1 receptor agonist outcomes to date, incorporating the latest SOUL and FLOW trial data. It definitively establishes that both injectable and oral GLP-1 RAs protect against heart disease, kidney disease, and death — not just lower blood sugar. The finding that oral formulations provide similar benefits to injections is particularly important, as it could dramatically expand patient access to these protective effects.","specificNumbers":"n=71,351 · 10 trials · MACE ↓14% (HR 0.86) · HHF ↓14% (HR 0.86) · kidney outcome ↓17% (HR 0.83) · mortality ↓12% (HR 0.88)","methodology":"The researchers conducted a systematic review of PubMed through February 2025, including all randomized placebo-controlled cardiovascular and kidney outcomes trials of long-acting GLP-1 receptor agonists with at least 500 participants with type 2 diabetes. Data from 10 trials were pooled using a random-effects model to estimate hazard ratios for cardiovascular events, heart failure, kidney outcomes, mortality, and safety endpoints.","limitations":"As a trial-level meta-analysis (rather than individual patient data), detailed subgroup analyses were not possible, and ecological bias may be present. The analysis could not examine whether specific patient populations benefit more than others."},{"rthcId":"RPEP-12022","title":"Disproportionality analysis of Raynaud's phenomenon associated with calcitonin gene-related peptide inhibitors using the Food and Drug Administration adverse event reporting system.","authors":"Lee, Nai; Ok, Ji Hoon; Rhee, Su-Jin; Kim, Yun","year":2025,"journal":"Scientific reports, 15(1), 5675","doi":"10.1038/s41598-025-87421-w","pmid":"39955348","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12023","title":"Identifying signals of disproportionate reporting for calcitonin gene-related peptide inhibitors: real-world evidence from the FDA adverse event reporting system.","authors":"Lee, Nai; Ok, Jihoon; Kwon, Yonghoon; Rhee, Su-Jin; Kim, Yun","year":2025,"journal":"Expert opinion on drug safety, 1-10","doi":"10.1080/14740338.2025.2497394","pmid":"40261259","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12024","title":"A Review of Amylin Peptide Receptor Activators for Obesity Pharmacotherapy.","authors":"Lee, Sangmin","year":2025,"journal":"Current drug targets, 26(14), 980-991","doi":"10.2174/0113894501398624250819070004","pmid":"40910290","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies several key developments in amylin receptor agonist research:\n\n• Amylin receptors are heterodimers of the calcitonin receptor and receptor activity-modifying proteins (RAMPs) — a unique and druggable receptor architecture\n• Multiple amylin analogs are in preclinical and clinical development for obesity\n• Combination therapy (amylin analog + other anti-obesity peptide drugs) has demonstrated higher clinical efficacy in reducing body weight than monotherapy\n• Combination therapy is likely to be the first clinical application where an amylin analog is used for obesity\n• Amylin receptor activators may have a more favorable adverse effect profile than GLP-1 receptor agonists\n• Key engineering advances: mutations enhancing receptor affinity/potency, lipidation for long-acting properties, and methods for measuring selective amylin receptor activation","whyItMatters":"GLP-1 drugs dominate the obesity market, but their GI side effects limit tolerability for many patients. Amylin agonists represent a genuinely different peptide mechanism — working through the calcitonin receptor/RAMP system rather than the GLP-1 receptor. If amylin drugs prove more tolerable, they could become preferred options or powerful combination partners. The finding that amylin + GLP-1 beats either alone suggests the future of obesity pharmacotherapy may involve multi-peptide cocktails.","specificNumbers":"","methodology":"Narrative review collecting recent research publications and drug development information on amylin receptor activators. Covers preclinical studies, clinical trials, receptor pharmacology, peptide engineering approaches, and combination therapy data.","limitations":"Narrative review without systematic methodology. Most amylin analog clinical data are from ongoing or recently completed trials with limited published details. The claim of fewer GI side effects versus GLP-1 drugs needs confirmation in head-to-head trials. Long-term safety data for amylin analogs in obesity are not available. The complexity of amylin receptor pharmacology (multiple RAMP subtypes) may complicate drug development."},{"rthcId":"RPEP-12025","title":"N-glycosylation effects on the function of class B1 G protein-coupled receptors.","authors":"Lee, Sangmin; Jin, Jeongwoo; Song, Hyeseon; Jang, Jaehyeok","year":2025,"journal":"Carbohydrate research, 557, 109641","doi":"10.1016/j.carres.2025.109641","pmid":"40803177","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review reveals that N-glycosylation enhances pharmacodynamic properties of class B1 GPCRs including receptor-ligand binding and activation potency. Key findings by receptor type:\n\n- Calcitonin and amylin receptors: N-glycosylation apparently enhanced binding affinity of peptide ligands, with specific critical N-glycosylation sites identified\n- GIP and secretin receptors: Also have critical individual N-glycosylation sites that drive the whole glycosylation effect\n- GLP-1 and CRF1 receptors: Each glycosylation site collectively contributes to the overall effect, rather than one site being dominant\n- Calcitonin gene-related peptide receptor: Has identified critical N-glycosylation sites\n\nThe review also addresses potential mechanisms by which sugar modifications enhance peptide ligand binding affinity at the molecular level.","whyItMatters":"Many of today's blockbuster peptide drugs — including semaglutide (GLP-1), tirzepatide (GIP/GLP-1), and calcitonin — work by binding to class B1 GPCRs. Understanding that sugar modifications on these receptors significantly affect how peptide drugs bind and activate them is essential for accurately evaluating drug potency and designing better therapeutics.","specificNumbers":"","methodology":"This is a narrative review summarizing published research on N-glycosylation effects across class B1 GPCR family members. The authors focused on three functional parameters: cell-surface receptor expression, ligand binding affinity, and receptor activation potency. They compared glycosylation patterns and functional dependencies across multiple receptor systems.","limitations":"The review notes that several class B1 GPCR family members remain unexplored regarding their N-glycosylation effects. Most studies reviewed used cell-based systems that may not perfectly replicate in vivo glycosylation patterns. The mechanisms by which glycosylation enhances binding remain incompletely understood."},{"rthcId":"RPEP-12026","title":"Effects of glucagon-like peptide-1 receptor agonists on psychiatric disorders: a systematic review.","authors":"Lee, Serene; Yin, Liyang; Teopiz, Kayla M; Wong, Sabrina; Han Le, Gia; Xiao, Naomi; Stahl, Stephen; Valentino, Kyle; Ho, Roger; Zhang, Melanie C; Greg Rhee, Taeho; McIntyre, Roger S","year":2025,"journal":"Therapeutic advances in psychopharmacology, 15, 20451253251396304","doi":"10.1177/20451253251396304","pmid":"41445693","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12027","title":"Glucagon-like Peptide-1 receptor agonists for the prevention and treatment of Parkinson's disease.","authors":"Lee, Serene; Yin, Liyang; Xiao, Naomi; Rhee, Taeho Greg; Lo, Heidi K Y; Wong, Sabrina; Fox, Susan; Teopiz, Kayla; Lam, Bess Yin-Hung; Zheng, Yang Jing; Le, Gia Han; Mansur, Rodrigo B; Rosenblat, Joshua D; McIntyre, Roger S","year":2025,"journal":"CNS spectrums, 30(1), e44","doi":"10.1017/S109285292510031X","pmid":"40485141","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12028","title":"The Impact of Glucagon-Like Peptide-1 Receptor Agonist Use on Clinical Outcomes After Total Hip and Knee Arthroplasty: A Systematic Review and Meta-Analysis of 346,899 Patients.","authors":"Lee, Seungjun; Singh, Kevin; Clark, Sean C; Goh, Graham S","year":2025,"journal":"The Journal of arthroplasty","doi":"10.1016/j.arth.2025.09.054","pmid":"41072556","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12029","title":"Impact of Glucagon-Like Peptide-1 Receptor Agonists on Postoperative Outcomes in Arthroplasty: A Systematic Review.","authors":"Lee, Vincent; Durkee, Stephen M; Ponce, Brent A; Coutelle, Nino; Gerges, Paul; Lima, Diego","year":2025,"journal":"The Journal of arthroplasty, 40(12), 3073-3079","doi":"10.1016/j.arth.2025.07.015","pmid":"40675511","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12030","title":"Effects of sacubitril/valsartan on hypertensive heart disease: the REVERSE-LVH randomized phase 2 trial.","authors":"Lee, Vivian; Dalakoti, Mayank; Zheng, Qishi; Toh, Desiree-Faye; Boubertakh, Redha; Bryant, Jennifer A; Aw, Tar-Choon; Lee, Chi-Hang; Richards, A Mark; Butler, Javed; Díez, Javier; Foo, Roger; Cook, Stuart A; Lam, Carolyn Sp; Le, Thu-Thao; Chin, Calvin Wl","year":2025,"journal":"Nature communications, 16(1), 6981","doi":"10.1038/s41467-025-62203-0","pmid":"40739095","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"At 52 weeks, sacubitril/valsartan produced a significantly greater absolute reduction in interstitial volume (a measure of cardiac fibrosis) compared to valsartan alone (-5.2 ± 5.4 vs. -2.5 ± 3.1 mL; P = 0.006), despite equivalent 24-hour systolic blood pressure (125 ± 11 vs. 126 ± 11 mmHg; P = 0.762). Secondary endpoints favoring sacubitril/valsartan included reductions in LV mass, left atrial volume, estimated LV filling pressure, NT-proBNP, and high-sensitivity troponin T.","whyItMatters":"Heart fibrosis — the buildup of scar tissue — is a key driver of heart failure in hypertensive patients, and until recently was considered largely irreversible. This trial provides randomized evidence that sacubitril/valsartan can reverse fibrosis beyond what blood pressure control alone achieves. The mechanism likely involves preserving natriuretic peptides (by inhibiting neprilysin), suggesting that boosting endogenous cardioprotective peptides has direct structural benefits on the heart.","specificNumbers":"","methodology":"REVERSE-LVH was a phase 2, open-label, randomized trial (NCT03553810). 78 patients with essential hypertension and left ventricular hypertrophy were randomized 1:1 to sacubitril/valsartan or valsartan for 52 weeks. The primary endpoint was change in interstitial volume assessed by cardiovascular magnetic resonance imaging. Secondary endpoints included cardiac volumes, function, mechanics, and circulating biomarkers.","limitations":"This was a small (n=78), open-label phase 2 trial without blinding, which introduces potential bias. The study was powered for imaging endpoints, not clinical outcomes like hospitalizations or mortality. The 52-week duration may not capture long-term fibrosis reversal or clinical benefits. The open-label design may have influenced patient behavior and clinician management decisions. Larger confirmatory trials are needed."},{"rthcId":"RPEP-12031","title":"The physiology of MASLD: molecular pathways between liver and adipose tissues.","authors":"Lee, Wang-Hsin; Kipp, Zachary A; Bates, Evelyn A; Pauss, Sally N; Martinez, Genesee J; Hinds, Terry D","year":2025,"journal":"Clinical science (London, England : 1979), 139(18), 1015-46","doi":"10.1042/CS20257571","pmid":"40985048","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12032","title":"Therapeutic Potential of Scolopendra subspinipes: A Comprehensive Scoping Review of Its Bioactive Compounds, Preclinical Pharmacology, and Clinical Applications.","authors":"Lee, Ye-Seul; Lee, Yoon Jae; Ha, In-Hyuk","year":2025,"journal":"Toxins, 17(5)","doi":"10.3390/toxins17050229","pmid":"40423312","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12033","title":"Association between autoimmune diseases and glucagon-like peptide-1 receptor agonists: A real-world evidence study.","authors":"Lee, Yun-Jui; Fang, Yu-Wei; Chen, Mon-Ting; Liou, Hung-Hsiang; Li, Tzu-Hao; Tsai, Ming-Hsien","year":2025,"journal":"Journal of autoimmunity, 155, 103453","doi":"10.1016/j.jaut.2025.103453","pmid":"40544585","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12034","title":"Neuroendocrine Regulation and Neural Circuitry of Parenthood: Integrating Neuropeptides, Brain Receptors, and Maternal Behavior.","authors":"Leff-Gelman, Philippe; Pellón-Díaz, Gabriela; Camacho-Arroyo, Ignacio; Palomera-Garfias, Nadia; Flores-Ramos, Mónica","year":2025,"journal":"International journal of molecular sciences, 26(18)","doi":"10.3390/ijms26189007","pmid":"41009573","tags":["oxytocin","neuropeptides"],"studyType":"Review","evidenceStrength":"moderate","keyFinding":"Maternal behavior is orchestrated by a network of neuropeptides — primarily oxytocin, prolactin, and placental lactogens — that physically reshape the mother's brain during pregnancy and the postpartum period. These peptides rewire neural circuits connecting the hypothalamus to reward centers (nucleus accumbens, ventral tegmental area), making infant cues intrinsically motivating and rewarding.\n\nProlactin's role extends far beyond milk production: it drives adult neurogenesis, neuroprotection, and neuroplasticity in the maternal brain. Other peptides including galanin, spexin, PACAP, CRH, and TIP-39 also contribute. Dysregulation of these neuropeptide systems is linked to postpartum psychiatric disorders.","whyItMatters":"Understanding how peptides wire the brain for parenthood has implications beyond basic science. Postpartum depression, anxiety, and psychosis affect millions of women, and disruptions in these neuropeptide systems may be root causes. This knowledge could lead to peptide-based treatments for postpartum mood disorders and bonding difficulties.","specificNumbers":"Review covering multiple neuropeptide systems: oxytocin, prolactin, placental lactogens, TIP-39, galanin, spexin, PACAP, CRH · neural circuits: PVN → mPOA → NAcc/VTA","methodology":"Comprehensive narrative review integrating molecular, cellular, and circuit-level evidence from animal models (primarily rodent studies) and human research. The review covers neuropeptide gene expression, receptor distribution, neural circuit tracing, and behavioral outcomes in postpartum females.","limitations":"Much of the mechanistic evidence comes from rodent models, which may not fully translate to human maternal behavior. The review is primarily descriptive and does not present new data. Human neuropeptide research is limited by the difficulty of measuring brain peptide levels in living subjects. The link between neuropeptide dysregulation and psychiatric disorders is correlational rather than definitively causal."},{"rthcId":"RPEP-12035","title":"The impact of oral semaglutide on cardiovascular events in patients with type 2 diabetes: review of results from the SOUL trial.","authors":"Lehenbauer, Katy S; Nelson, Adam J; Nodari, Savina; Sverdlov, Aaron L; Harrington, Josephine","year":2025,"journal":"Heart failure reviews, 31(1), 11","doi":"10.1007/s10741-025-10579-y","pmid":"41370018","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The SOUL trial demonstrated that oral semaglutide (14 mg daily) significantly reduced the risk of major adverse cardiovascular events (MACE) by 14% compared to placebo in 9,650 high-risk adults with type 2 diabetes (HR 0.86, 95% CI 0.77-0.96, p=0.006). The primary composite outcome included cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. The benefit was consistent across subgroups, including those already taking SGLT2 inhibitors. This was the first trial to establish cardiovascular benefit for an oral GLP-1 receptor agonist.","whyItMatters":"Until SOUL, cardiovascular benefit had only been proven for injectable GLP-1 drugs. This trial proves that a daily pill form of semaglutide provides the same cardiovascular protection, which could dramatically expand access to this life-saving peptide therapy. Many patients prefer pills over injections, and an oral option with proven heart benefits removes a major barrier to GLP-1 RA adoption.","specificNumbers":"n=9,650 · oral semaglutide 14 mg vs placebo · MACE HR 0.86 (95% CI 0.77-0.96, p=0.006) · median follow-up 49.5 months · T2DM with ASCVD and/or CKD · consistent across SGLT2i subgroups","methodology":"SOUL was a randomized, double-blind, placebo-controlled superiority trial. 9,650 adults with type 2 diabetes and established atherosclerotic cardiovascular disease, chronic kidney disease, or both were randomized to oral semaglutide 14 mg daily or placebo. The primary outcome was time to first cardiovascular death, non-fatal MI, or non-fatal stroke. Prespecified secondary analyses assessed expanded cardiovascular, kidney, peripheral artery, and heart failure outcomes. Median follow-up was 49.5 months.","limitations":"This is a review of the SOUL trial, not the primary trial publication itself. The trial enrolled only high-risk T2DM patients with established cardiovascular or kidney disease, so results may not generalize to lower-risk populations. The oral semaglutide dose (14 mg) may not have the same cardiovascular effect as higher injectable doses. Long-term effects beyond the median 49.5-month follow-up are unknown."},{"rthcId":"RPEP-12036","title":"The therapeutic potential of glucagon-like peptide-1 receptor analogs for neuroinflammation in the setting of asthma.","authors":"Lehman, Courtney; Peebles, Ray Stokes","year":2025,"journal":"Exploration of asthma & allergy, 3","doi":"10.37349/eaa.2025.100967","pmid":"40474934","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12037","title":"Amphipathic Octenyl-Alanine Modified Peptides Mediate Effective siRNA Delivery.","authors":"Lehto, Tõnis; Isakannu, Marit; Sork, Helena; Lorents, Annely; Bazaz, Safa; Wiklander, Oscar P B; Andaloussi, Samir El; Lehto, Taavi","year":2025,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 31(10), e70054","doi":"10.1002/psc.70054","pmid":"40915857","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12038","title":"Multifunctional cyclic biomimetic peptides: Self-assembling nanotubes for effective treatment of sepsis.","authors":"Lei, Ruyi; Yang, Chujun; Zhu, Tao; Zhu, Xingqiang; Zhu, Zhiqiang; Cui, Hongwei; Pei, Hui; Li, Jiye; Mao, Yujing; Lan, Chao","year":2025,"journal":"International journal of biological macromolecules, 288, 138522","doi":"10.1016/j.ijbiomac.2024.138522","pmid":"39672431","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12039","title":"Clinical score based on CGRP, PD-1, and PD-L1 for PICC-related bloodstream infections in breast cancer.","authors":"Lei, Shuang-Gen; Zhu, Da-Qing; Jiang, Qi-Hua; Tan, Jun-Tao; Hu, Ping-Hua","year":2025,"journal":"Scientific reports, 15(1), 43324","doi":"10.1038/s41598-025-27362-6","pmid":"41360843","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12040","title":"Development and Validation of a Mortality Prediction Model for Left Ventricular Thrombus.","authors":"Lei, Song; Yu, Chenyu; Li, Li; Liu, Mei; Yang, Mou; Hu, Hongde","year":2025,"journal":"Pacing and clinical electrophysiology : PACE, 48(9), 1024-1036","doi":"10.1111/pace.70014","pmid":"40778530","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12041","title":"Structure, function, and therapeutic potential of defensins from marine animals.","authors":"Lei, Yining; He, Dangui; Zhao, Xiao; Miao, Lixia; Cao, Zhijian","year":2025,"journal":"Fish & shellfish immunology, 163, 110365","doi":"10.1016/j.fsi.2025.110365","pmid":"40318710","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies several key aspects of marine animal defensins:\n\n• Marine defensins exhibit activity against bacteria, viruses, and fungi through multiple mechanisms — membrane binding, channel formation, and lipid II interaction\n• The ocean's unique ecological environment has produced defensins with rich biodiversity and special molecular features compared to terrestrial defensins\n• Beyond antimicrobial activity, marine defensins also have immune-regulatory and reproductive functions\n• Nanotechnology approaches — including antimicrobial peptide-antibiotic conjugates, nanonets, and nanoparticle-based delivery systems — can enhance their antibacterial potency and broaden their spectrum of activity\n• Marine defensins are classified primarily from fish and shellfish sources, with distinct structural characteristics and evolutionary trajectories","whyItMatters":"Antibiotic resistance threatens to make common infections untreatable. Antimicrobial peptides like defensins kill bacteria through mechanisms that are fundamentally different from conventional antibiotics, making it much harder for bacteria to develop resistance. Marine organisms — which have survived in pathogen-rich ocean environments for hundreds of millions of years — represent a largely untapped reservoir of these natural antibiotics. Understanding and harnessing marine defensins could provide new weapons against drug-resistant superbugs.","specificNumbers":"","methodology":"This is a narrative review that synthesizes published research on defensins from marine animals. The authors compiled and analyzed data on structural characteristics, classification, evolutionary history, antimicrobial mechanisms, immune functions, and therapeutic applications of marine defensins, with emphasis on fish and shellfish sources.","limitations":"As a review article, this synthesizes existing research without generating new experimental data. Most marine defensin research is at the in vitro stage — very few marine-derived defensins have reached preclinical or clinical testing. The translation from discovering an antimicrobial peptide in a fish to developing a human therapy faces enormous challenges including stability, toxicity, manufacturing cost, and regulatory approval. The review focuses primarily on fish and shellfish, potentially underrepresenting defensins from other marine organisms."},{"rthcId":"RPEP-12042","title":"Peptides as Versatile Regulators in Cancer Immunotherapy: Recent Advances, Challenges, and Future Prospects.","authors":"Lei, Yu; Liu, Jiacheng; Bai, Yaowei; Zheng, Chuansheng; Wang, Dongyuan","year":2025,"journal":"Pharmaceutics, 17(1)","doi":"10.3390/pharmaceutics17010046","pmid":"39861694","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12043","title":"Oxytocin: a neglected hormone in pituitary disease - From function to the diagnosis of a deficiency, resulting clinical relevance, and potential treatment options in endocrinology.","authors":"Leibnitz, Svenja; Christ-Crain, Mirjam; Atila, Cihan","year":2025,"journal":"Archives of endocrinology and metabolism, 70(special 1), e20250259","doi":"10.20945/2359-4292-2025-0259","pmid":"41313193","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12044","title":"FDG PET/CT Images Demonstrating Subclinical Pancreatitis in a Patient on a GLP-1 Receptor Agonist.","authors":"Lenkov, Robert; Berman, Tyler; Mehmi, Inderjit; Mehta, Pareen","year":2025,"journal":"Clinical nuclear medicine, 50(11), 1069-1070","doi":"10.1097/RLU.0000000000005856","pmid":"40103000","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"FDG PET/CT imaging revealed diffuse increased radiotracer uptake throughout the pancreas in a clinically asymptomatic 83-year-old man. Standard CT showed no structural abnormality, but subsequent lipase testing confirmed subclinical pancreatitis. The patient was taking tirzepatide (a dual GIP/GLP-1 receptor agonist), and after excluding other potential causes, the pancreatitis was attributed to this medication.\n\nThis case demonstrates that GLP-1 receptor agonist-associated pancreatitis can be entirely subclinical — detectable only through metabolic imaging or laboratory testing, not symptoms.","whyItMatters":"Pancreatitis is a known but debated risk associated with GLP-1 receptor agonists — medications now taken by millions of people for diabetes and weight loss. This case is notable because the pancreatitis was completely silent (no symptoms), raising the question of how often this occurs undetected. If subclinical pancreatitis is more common than recognized, it could have implications for long-term monitoring of patients on GLP-1 medications.","specificNumbers":"","methodology":"This is a case report. An 83-year-old man with basal cell carcinoma was referred for 18F-FDG PET/CT staging. The incidental pancreatic finding prompted follow-up lipase measurement. The clinical team reviewed the patient's medication list and medical history to identify potential causes of pancreatitis, ultimately attributing it to tirzepatide after excluding other etiologies.","limitations":"As a single case report, this provides the lowest level of clinical evidence and cannot establish causation between tirzepatide and pancreatitis. The patient was elderly (83 years), which is itself a risk factor for pancreatitis. The finding was incidental — no systematic screening was performed. Without larger studies, it is impossible to know how common subclinical pancreatitis is among GLP-1 receptor agonist users."},{"rthcId":"RPEP-12045","title":"SAAP-148 and halicin exhibit synergistic antimicrobial activity against antimicrobial-resistant bacteria in skin but not airway epithelial culture models.","authors":"Lennard, Patrick R; Hiemstra, Pieter S; Dorin, Julia R; Nibbering, Peter H","year":2025,"journal":"JAC-antimicrobial resistance, 7(2), dlaf050","doi":"10.1093/jacamr/dlaf050","pmid":"40224359","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12046","title":"Hederagenin is a Highly Selective Antagonist of the Neuropeptide FF Receptor 1 that Reveals Mechanisms for Subtype Selectivity.","authors":"Lentschat, Hannah; Liessmann, Fabian; Tydings, Claiborne; Schermeng, Tina; Stichel, Jan; Urban, Nicole; Schaefer, Michael; Meiler, Jens; Beck-Sickinger, Annette G","year":2025,"journal":"Angewandte Chemie (International ed. in English), 64(6), e202417786","doi":"10.1002/anie.202417786","pmid":"39641914","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12047","title":"Moving for optimal immunity: the effect of acute high-intensity interval training on phenotype, virus specificity and chemokine receptor expression in human CD8+ T cells.","authors":"Leuchte, Katharina; Luu, Thy Viet; Fresnillo Saló, Sara; Madsen, Kasper; Heide-Ottosen, Lise; Skadborg, Signe Koggersbøl; Kemming, Janine Sophie; Holmström, Morten Orebo; Chen, Hongjin; Olsen, Lars Rønn; Vinther, Anders; Andersen, Mads Hald; Hadrup, Sine Reker; Thor Straten, Per; Holmen Olofsson, Gitte","year":2025,"journal":"Frontiers in immunology, 16, 1739657","doi":"10.3389/fimmu.2025.1739657","pmid":"41675500","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12048","title":"Clinical Experience with Targeted Alpha-Emitter Peptide Receptor Radionuclide Therapy (α-PRRT) for Somatostatin Receptor-Positive Neuroendocrine Tumors.","authors":"Leupe, Hannes; Cauwenbergh, Merel; Cleeren, Frederik; Dekervel, Jeroen; Verslype, Chris; Deroose, Christophe M","year":2025,"journal":"Pharmaceuticals (Basel, Switzerland), 18(11)","doi":"10.3390/ph18111608","pmid":"41304857","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12049","title":"Effect of Injectable Dual and Single Agonist Glucagon-Like Peptide-1 Based Therapy on Inflammatory Bowel Disease Activity Among Patients with Obesity.","authors":"Levine, Jake; Lee, Yao An; Pham, Angela; Guo, Jingchuan; Dai, Hao; Radwan, Rotana M; Bian, Jiang; Novikov, Aleksey; Sheer, Amy","year":2025,"journal":"medRxiv : the preprint server for health sciences","doi":"10.1101/2025.11.13.25340005","pmid":"41292626","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide use was associated with a 67% reduction in IBD-related surgery risk (HR 0.33, 95% CI 0.13-0.83). Among 89 tirzepatide users, none required IBD-related surgery (versus 2 matched controls), though the sample size was too small for statistical significance. GLP-1 use significantly reduced serum C-reactive protein (CRP), suggesting anti-inflammatory effects. No differences were found in all-cause hospitalization, IBD-hospitalization, or pancreatitis rates between GLP-1 users and non-users overall.\n\nNotably, Black GLP-1 users had increased all-cause hospitalization risk (HR 1.59, CI 1.11-2.29) but not IBD-specific hospitalization or surgery, suggesting factors beyond IBD may be driving this disparity.","whyItMatters":"Obesity worsens IBD outcomes, and many IBD patients are obese. This is among the first studies to examine whether GLP-1 receptor agonists — already taken by many obese patients — could have secondary benefits for IBD management. The finding that semaglutide reduced surgery risk by 67% suggests these peptide drugs may have clinically meaningful anti-inflammatory effects relevant to autoimmune gut conditions.","specificNumbers":"","methodology":"Retrospective propensity-matched cohort study using the OneFlorida+ clinical data network. 562 patients with IBD and obesity who were prescribed GLP-1-based therapy (liraglutide, semaglutide, or tirzepatide) were matched 1:1 to controls based on demographics and comorbidities. Outcomes assessed included all-cause hospitalization, IBD-related hospitalization, IBD-related surgery, pancreatitis, steroid use, and serum CRP levels.","limitations":"This is a retrospective observational study (preprint, not yet peer-reviewed), which cannot establish causation. The tirzepatide group was small (n=89), limiting conclusions about this drug specifically. The propensity matching may not account for all confounders. The racial disparity in hospitalization risk needs further investigation. As a preprint on medRxiv, the findings have not undergone formal peer review."},{"rthcId":"RPEP-12050","title":"Glucagon-Like Peptide-1 Receptor Agonists among Pregnancies with Pregestational Diabetes and Its Relationship with Congenital Malformations.","authors":"Lewin, Zoe; Snow, Shani; Lee, Jung Ae; Wilkie, Gianna","year":2025,"journal":"American journal of perinatology","doi":"10.1055/a-2716-1639","pmid":"41052622","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12051","title":"Semaglutide and Postoperative Outcomes in Nondiabetic Patients Following Body Contouring Surgery.","authors":"Lewis, Joshua E; Ghogomu, Mbinui; Hickman, Stanley J; Ashade, Adedamola; Hollis, Raven J; Lewis, Jimmie E; Lee, Wei-Chen","year":2025,"journal":"Aesthetic surgery journal, 45(4), 381-386","doi":"10.1093/asj/sjae241","pmid":"39665435","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12052","title":"The impact of semaglutide on wound healing in diabetes related foot ulcer patients: A TriNetX database study.","authors":"Lewis, Joshua E; Omenge, Diana K; Patterson, Amani R; Anwaegbu, Ogechukwu; Tabukum, Nangah N; Lewis, Jimmie E; Lee, Wei-Chen","year":2025,"journal":"Diabetes & vascular disease research, 22(2), 14791641251322909","doi":"10.1177/14791641251322909","pmid":"40080656","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12053","title":"Sex differences in the effects of calcitonin gene-related peptide signaling on migraine-like behavior in animal models: a narrative review.","authors":"Lewter, Lakeisha A; Arnold, Rachel L; Narosov, Nina B; Dussor, Gregory; Kolber, Benedict J","year":2025,"journal":"Frontiers in neurology, 16, 1603758","doi":"10.3389/fneur.2025.1603758","pmid":"40708951","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12054","title":"The role of amygdala calcitonin gene-related peptide receptors on the development of persistent bladder pain in mice.","authors":"Lewter, Lakeisha A; Paul, Blesson K; Salazar, Arnold M; Chatterjee, Uma; Pham, Hoai Phuong T; Khan, Myra Z; Schmitz, Anna E; Nofal, Abraham M; Hussein, Mursal M; Mysorekar, Indira U; Kolber, Benedict J","year":2025,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2025.06.10.658965","pmid":"40661352","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12055","title":"Is Semaglutide Linked to NAION? A Case Report on a Rare Ocular Complication.","authors":"Lešin Gaćina, Dina; Vidović, Tomislav; Vlajić Oreb, Nikolina; Matković, Lovorka; Jandroković, Sonja","year":2025,"journal":"Reports (MDPI), 8(3)","doi":"10.3390/reports8030149","pmid":"40843891","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12056","title":"FAP deficiency attenuates T2DM-associated HFpEF by suppressing the CaMKIIδ-Calcineurin A-NFATc2 signaling pathway.","authors":"Li, Chao; Han, Xiao; He, Jia-Kang; Tang, Sheng-Xing; Zhang, Yun-Long; Yu, Xiao-Hong; Gao, Lian-Jun","year":2025,"journal":"Clinical science (London, England : 1979), 139(17), 923-940","doi":"10.1042/CS20256808","pmid":"40855978","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12057","title":"Engineered Lactococcus lactis biovaccine containing NY-ESO-1 long peptides as potent immunotherapeutics.","authors":"Li, Chunyi; Wang, Kongcheng; Shao, Jie; Zhu, Junmeng; Ke, Yaohua; Liu, Baorui; Cen, Lanqi","year":2025,"journal":"Materials today. Bio, 35, 102440","doi":"10.1016/j.mtbio.2025.102440","pmid":"41281658","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12058","title":"BioJect: An in vitro platform to explore release dynamics of peptides in subcutaneous drug delivery.","authors":"Li, David; Qin, Qiuhua; Benetti, Ayça Altay; Kahouadji, Lyes; Wacker, Matthias G","year":2025,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 380, 1058-1079","doi":"10.1016/j.jconrel.2025.02.013","pmid":"39923852","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12059","title":"Mast cell-neuron axis as a core mechanism in chronic pruritus of atopic dermatitis: from mechanistic insights to therapeutic targets.","authors":"Li, Dongdong; Han, Yusheng; Zhou, Jingjing; Yang, Huasen; Chen, Jing; Tey, Hong Liang; Tan, Timothy T Y","year":2025,"journal":"Frontiers in immunology, 16, 1645095","doi":"10.3389/fimmu.2025.1645095","pmid":"41235218","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12060","title":"Lipid level stabilization following combination therapy with IdaGlar and Semaglutide in type 2 diabetes: a retrospective study.","authors":"Li, Fangfang; Li, Junmiao; Liu, Jie","year":2025,"journal":"American journal of translational research, 17(12), 9441-9450","doi":"10.62347/TZRY3855","pmid":"41552324","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12061","title":"Multifunctional self-emulsifying drug delivery system: an efficient strategy for oral delivery of therapeutic peptides and proteins.","authors":"Li, Guofei; Shao, Changyu; Zhang, Yuhao; Li, Jinguo; Wang, Puxiu; Ren, Tianyang","year":2025,"journal":"Drug delivery, 32(1), 2579137","doi":"10.1080/10717544.2025.2579137","pmid":"41369159","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12062","title":"The CRISPR/Cas13a-assisted electrochemiluminescence sensing device combined with entropy-driven and hybrid chain reaction nucleic acid amplification techniques for ultra-sensitive analysis of brain natriuretic peptide.","authors":"Li, Haixiang; Lian, Shuo; Zhang, Zhiwei; Bi, Weiye; Meng, Qingyou; Ding, Qingwei","year":2025,"journal":"Talanta, 295, 128310","doi":"10.1016/j.talanta.2025.128310","pmid":"40393243","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12063","title":"Development of Hydrogen Sulfide-Donating Silybin Derivatives with a Type-2 Diabetes Mellitus-Alleviating Effect through Improving Intestinal L-Cell Functions.","authors":"Li, Haonan; Ma, Qingyinglu; Li, Xu; Zheng, Chao; Lin, Lang; Gu, Jia; Huang, Xiaofang; Yang, Hangao; Xu, Huarong; Xu, Fanxing; Hua, Huiming; Cheng, Maosheng; Li, Dahong","year":2025,"journal":"Journal of medicinal chemistry, 68(15), 15520-15542","doi":"10.1021/acs.jmedchem.5c00194","pmid":"40759002","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12064","title":"Oxytocin lipidation expanding therapeutics for long-term reversal of autistic behaviors in rats.","authors":"Li, Honglin; Chen, Ya; Qiu, Yue","year":2025,"journal":"International journal of pharmaceutics, 672, 125299","doi":"10.1016/j.ijpharm.2025.125299","pmid":"39890086","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12065","title":"The Relationship Between BigET-1 and Cardiac Remodeling in Patients with Hypertrophic Obstructive Cardiomyopathy.","authors":"Li, Hua; Cao, Xiao; Wu, Hao; Dong, Dandan","year":2025,"journal":"Molecular biotechnology, 67(11), 4203-4211","doi":"10.1007/s12033-024-01308-1","pmid":"39557775","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12066","title":"Emerging Trends and Future Prospects of Peptide-Based Hydrogels: Revolutionizing Food Technology Applications.","authors":"Li, Huanhuan; Murugesan, Arul; Shoaib, Muhammad; Chen, Quansheng","year":2025,"journal":"Comprehensive reviews in food science and food safety, 24(3), e70187","doi":"10.1111/1541-4337.70187","pmid":"40371450","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12067","title":"Cathelicidin-HG alleviates psoriasis by targeting glycoprotein VI to inhibit platelet-neutrophil complexes formation.","authors":"Li, Jiali; Xiong, Weichen; Yang, Jianxi; Gao, Yihan; Chai, Jinwei; Tian, Maolin; Chu, Xinwei; Huang, Xiaowen; Kotsyfakis, Michail; Chen, Xin; Xu, Xueqing","year":2025,"journal":"European journal of pharmacology, 991, 177330","doi":"10.1016/j.ejphar.2025.177330","pmid":"39892446","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12068","title":"Dissecting the geometric and hydrophobic constraints of stapled peptides.","authors":"Li, Jianguo; Tan, Yaw Sing; Verma, Chandra S","year":2025,"journal":"Proteins, 93(1), 287-301","doi":"10.1002/prot.26662","pmid":"38196284","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12069","title":"Advances in Cancer Vaccines for Digestive System Cancers: A Systematic Analysis of Clinical Trials.","authors":"Li, Jianing; Wang, Peili","year":2025,"journal":"Cancer management and research, 17, 2691-2703","doi":"10.2147/CMAR.S561298","pmid":"41245584","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12070","title":"A Multifunctional Nanodelivery System Modified by Fusion Peptides Acts as Teriparatide Carrier for Noise-Induced Hearing Loss Therapy.","authors":"Li, Jiawen; Hao, Zhuowen; Ke, Fangzi; Liu, Zhihui; Wang, Weilong; Wen, Sihui; Wu, Fan; Xu, Bowen; He, Miao; Zou, Shengyu; Chen, Xiong; Li, Jingfeng; He, Zuhong","year":2025,"journal":"Advanced science (Weinheim, Baden-Wurttemberg, Germany), 12(29), e2408798","doi":"10.1002/advs.202408798","pmid":"39921275","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12071","title":"Release pattern of potent dipeptidyl peptidase IV(DPP-IV) inhibitory peptides from tilapia (Oreochromis niloticus) skin collagen.","authors":"Li, Jiaxin; Yang, Danyin; Xu, Qiongyao; Huang, Mingtao; Zheng, Lin; Zhao, Mouming","year":2025,"journal":"Food chemistry, 489, 144970","doi":"10.1016/j.foodchem.2025.144970","pmid":"40450856","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"ProteaC-digested collagen hydrolysate showed the highest DPP-IV inhibitory activity with an IC50 of 0.58 ± 0.02 mg/mL. The enzyme preferentially cleaved at glycine and hydrophobic amino acid residues at the P1' position and showed strong preference for hydroxyproline at the P1 position. Large amounts of Gly-Pro-type peptides consisting of 4, 6, and 9 amino acids were released. The dynamic release followed a clear pattern: precursor peptides → target active peptides → shorter peptides.","whyItMatters":"DPP-IV inhibitors are a major class of diabetes medications. Understanding how natural DPP-IV inhibitory peptides are released from food proteins like collagen could lead to functional foods or nutraceuticals that help manage blood sugar. This study provides the mechanistic blueprint for optimizing that release process.","specificNumbers":"","methodology":"Researchers used tilapia skin collagen as a starting material and tested multiple proteases to determine which released the most potent DPP-IV inhibitory peptides. They analyzed cleavage selectivity of each enzyme and tracked the dynamic release mechanism of Gly-Pro-type peptides over the course of digestion. DPP-IV inhibitory activity was measured using IC50 values.","limitations":"This is an in vitro biochemistry study — the DPP-IV inhibitory activity was measured in a test tube, not in living organisms. Whether these peptides survive further digestion in the human gut, get absorbed intact, and reach effective concentrations in the bloodstream is unknown. The IC50 value represents enzyme inhibition in isolation, not a clinical blood sugar effect."},{"rthcId":"RPEP-12072","title":"A real-world disproportionality analysis of tirzepatide-related adverse events based on the FDA Adverse Event Reporting System (FAERS) database.","authors":"Li, Jie; Xie, Jun; Han, Yi; Zhang, Wei; Wang, Yilei; Jiang, Zhitao","year":2025,"journal":"Endocrine journal, 72(3), 273-283","doi":"10.1507/endocrj.EJ24-0286","pmid":"39603650","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12073","title":"Two Antihypertensive and Antioxidant Peptides Derived from Alaska Pollack (Theragra chalcograma) Skin: In Silico, In Vitro, and In Vivo Investigation.","authors":"Li, Jing; Cai, Duo; Zhai, Yong-Nian; Wu, Chen-Xi; Zhang, Hai-Lin; Zhang, Jian; Liu, Cheng-Lin; Liu, Shi-Hai; Qu, Jian-Bo","year":2025,"journal":"Journal of agricultural and food chemistry, 73(16), 9932-9945","doi":"10.1021/acs.jafc.5c00166","pmid":"40207866","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12074","title":"Activation of cyclooxygenase-2 signaling mediates liraglutide-induced adipose lipolytic activity.","authors":"Li, Jingyi; Wu, Hailian; Ma, Wenhui; Yuan, Tao; Chen, Xiaopan; Pan, Yong","year":2025,"journal":"European journal of pharmacology, 1006, 178133","doi":"10.1016/j.ejphar.2025.178133","pmid":"40935112","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Liraglutide (1 mg/kg/day) improved insulin resistance and reduced body weight and fat mass in high-fat diet-induced obese mice. At the cellular level, liraglutide suppressed adipocyte hypertrophy (fat cell enlargement) and upregulated browning markers PGC1α, UCP1, and ATGL in both obese adipose tissues and cultured 3T3-L1 adipocytes.\n\nMetabolomics analysis revealed that liraglutide elevated COX-2 signaling and prostaglandin levels in subcutaneous fat. Critically, COX-2 inhibition completely abolished liraglutide's effects on adipogenesis and lipolysis, and impaired adaptive thermogenesis during cold exposure. This demonstrates that COX-2 activation is required for liraglutide's fat-burning effects.","whyItMatters":"Understanding how GLP-1 drugs burn fat is crucial for optimizing their use and predicting drug interactions. The finding that COX-2 is essential for liraglutide's fat-metabolizing effects has immediate clinical implications: millions of patients take COX-2 inhibitors (like celecoxib) or NSAIDs (like ibuprofen) alongside GLP-1 agonists. If these anti-inflammatory drugs blunt the fat-burning benefits of GLP-1 therapies, it could affect treatment outcomes for obese patients.","specificNumbers":"","methodology":"In vivo: High-fat diet-induced obese mice received liraglutide (1 mg/kg/day) and were assessed for metabolic parameters, body weight, fat mass, and adipose tissue histology. In vitro: Differentiated 3T3-L1 adipocytes were treated with liraglutide with and without COX-2 inhibition. Non-targeted metabolomics was performed on subcutaneous adipose tissue. Cold exposure experiments tested the role of COX-2 in adaptive thermogenesis.","limitations":"This is a mouse study using a single dose of liraglutide, and results may not directly translate to humans. The specific COX-2 inhibitor used and its dosing were not detailed in the abstract. Whether this mechanism applies equally to other GLP-1 receptor agonists (semaglutide, tirzepatide) was not tested. The clinical significance of COX-2 involvement in human patients taking GLP-1 drugs remains to be established."},{"rthcId":"RPEP-12075","title":"Common genetic variants near SLC2A2 and glycemic response to glimepiride in the GRADE comparative effectiveness clinical trial.","authors":"Li, Josephine H; Szczerbinski, Lukasz; Tripputi, Mark; Liu, Haiyin; Nam, Stella; Mujica, Endrina; Emmanouilidou, Anastasia; Wangden, Thinley Yidzin; Citko-Rojewska, Anna; Konopka, Paulina; Czajkowski, Marcin; Huerta-Chagoya, Alicia; Vora, Maheak; Leong, Aaron; Meigs, James B; Ng, Maggie Y; Loos, Ruth J F; Pigeyre, Marie; Gerstein, Hertzel C; Moura, Filipe A; Lai, Yi-Pin; Bhatt, Deepak L; Marston, Nicholas A; Ruff, Christian T; Sabatine, Marc S; Dawed, Adam Y; Pearson, Ewan R; Satin, Leslie S; den Hoed, Marcel; Kretowski, Adam; Kahn, Steven E; Younes, Naji; Mercader, Josep M; Florez, Jose C","year":2025,"journal":"medRxiv : the preprint server for health sciences","doi":"10.1101/2025.10.07.25336827","pmid":"41282760","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12076","title":"Effective treatment for fatty liver of liraglutide via inhibiting endoplasmic reticulum stress, oxidative stress and apoptosis pathways.","authors":"Li, Juan; Xu, Jiaxin; Zhu, Fangfang; Wang, Chun","year":2025,"journal":"Archives of medical science : AMS, 21(4), 1432-1448","doi":"10.5114/aoms/186658","pmid":"41078944","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12077","title":"ACE inhibitory casein peptide lowers blood pressure and reshapes gut microbiota in a randomized double blind placebo controlled trial.","authors":"Li, Kexin; Jiang, Peng; Li, Shuangqi; Sun, Jin; Qi, Ce","year":2025,"journal":"Scientific reports, 15(1), 13840","doi":"10.1038/s41598-025-98446-6","pmid":"40263513","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12078","title":"Benefits of glucagon-like peptide-1 receptor agonists versus pioglitazone for cardio-hepatic outcomes: a territory-wide target trial emulation.","authors":"Li, Lanlan; Lui, David Tak-Wai; Fong, Carol Ho-Yi; Chow, Wing-Sun; Au, Ivan Chi-Ho; Xiong, Xi; Lang, Brian Hung-Hin; Wong, Carlos King-Ho; Lee, Chi-Ho","year":2025,"journal":"Cardiovascular diabetology, 24(1), 416","doi":"10.1186/s12933-025-02973-5","pmid":"41174643","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 8,922 propensity-matched patients (4,461 per group), GLP-1 receptor agonists showed comparable risks versus pioglitazone for major adverse liver outcomes (HR 0.94, 95% CI 0.66–1.34) and MACE (HR 0.99, 95% CI 0.80–1.22). However, GLP-1 receptor agonists significantly reduced heart failure risk (HR 0.65, 95% CI 0.51–0.83) — a 35% reduction. Results were consistent across intention-to-treat and per-protocol analyses and robust across subgroup analyses.","whyItMatters":"Both GLP-1 receptor agonists and pioglitazone are recommended for patients with type 2 diabetes and cardiovascular or liver disease risk. Without head-to-head trials, clinicians have lacked direct comparison data. This study fills that gap and provides actionable guidance — especially the finding that GLP-1 drugs have a meaningful edge in preventing heart failure.","specificNumbers":"","methodology":"This was a target trial emulation using an active comparator, new user design. Type 2 diabetes patients newly prescribed GLP-1 receptor agonists or pioglitazone between 2008 and 2022 were identified from a territory-wide Hong Kong health database. Propensity score matching created balanced groups, and Cox proportional hazards models estimated outcomes via both intention-to-treat and per-protocol analyses.","limitations":"This is an observational study using electronic health records, not a randomized trial, so unmeasured confounders may exist. The study was conducted in a Hong Kong Chinese population, which may limit generalizability. Specific GLP-1 drugs were not analyzed separately, and the per-protocol heart failure result did not reach significance, suggesting the ITT finding should be interpreted cautiously."},{"rthcId":"RPEP-12079","title":"Advances in Hydrocarbon Stapled Peptides via Ring-Closing Metathesis: Synthetic Strategies, Structural Diversity, and Therapeutic Applications.","authors":"Li, Linji; Li, Rong; Jiang, Yanan; Chao, Jingru; Chen, Si; Liao, Hongli; Li, Xiang","year":2025,"journal":"Chembiochem : a European journal of chemical biology, 26(23), e202500527","doi":"10.1002/cbic.202500527","pmid":"41031536","tags":["peptide-engineering","drug-discovery"],"studyType":"review","evidenceStrength":"n/a-review","keyFinding":"Hydrocarbon stapling — using a chemical 'staple' to lock peptides into their spiral (alpha-helical) shape — has become the most widely adopted peptide stabilization strategy. The technique uses ruthenium-catalyzed ring-closing metathesis, a chemical reaction that forms a hydrocarbon bridge across one face of the peptide helix.\n\nRecent advances include multiple-stapling (more than one staple per peptide), stitched peptides, aza-stapled peptides, and the integration of rigid anchoring amino acids that expand structural diversity. New modifications also enable imaging capabilities, such as Raman-active diyne bridges for diagnostic applications.","whyItMatters":"Regular peptides are floppy and get chewed up by enzymes in the body, limiting their use as drugs. Stapling locks them into their active shape, making them more stable, better at crossing cell membranes, and more biologically potent. This matters because stapled peptides can target protein-protein interactions — a class of drug targets that traditional small molecules largely can't reach, opening up treatment possibilities for cancers and other diseases.","specificNumbers":"Most widely adopted stapling method · Ruthenium-catalyzed RCM · Strategies: mono-stapling, multi-stapling, stitched, aza-stapled · Compatible with solid-phase peptide synthesis","methodology":"Review article summarizing advancements in hydrocarbon stapled peptide technology, covering synthetic strategies, structural innovations, and therapeutic/diagnostic applications.","limitations":"As a review, no new experimental data is presented. The review focuses on chemical methodology and may not fully address in vivo efficacy or clinical translation challenges. Many stapled peptide candidates are still in early development."},{"rthcId":"RPEP-12080","title":"Glucagon-Like Peptide-1 Receptor-Targeted PET/CT With 68 Ga-HBED-CC-Exendin-4 in Localizing Insulinoma : A Head-to-Head Comparison to 68 Ga-NOTA-Exendin-4.","authors":"Li, Linlin; Wang, Guochang; Wang, Jiarou; Ma, Heng; Chen, Jingci; Wang, Rongxi; Pan, Qingqing; Hong, Haiyan; Jin, Wenbin; Kung, Hank F; Zhu, Lin; Luo, Yaping; Zhu, Zhaohui","year":2025,"journal":"Clinical nuclear medicine, 50(1), 38-43","doi":"10.1097/RLU.0000000000005533","pmid":"39499011","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12081","title":"Semaglutide enhances PINK1/Parkin‑dependent mitophagy in hypoxia/reoxygenation‑induced cardiomyocyte injury.","authors":"Li, Liqin; Jin, Lili; Tian, Yaping; Wang, Jun","year":2025,"journal":"Molecular medicine reports, 31(5)","doi":"10.3892/mmr.2025.13476","pmid":"40017118","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12082","title":"The antimicrobial peptide Cec4 has therapeutic potential against clinical carbapenem-resistant Klebsiella pneumoniae.","authors":"Li, Lu; Zeng, Yang; Tian, Minfang; Cao, Huijun; Qiu, Zhilang; Guo, Guo; Shen, Feng; Wang, Yuping; Peng, Jian","year":2025,"journal":"Microbiology spectrum, 13(7), e0273824","doi":"10.1128/spectrum.02738-24","pmid":"40377314","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Cec4 demonstrated comprehensive activity against carbapenem-resistant Klebsiella pneumoniae through multiple mechanisms:\n\n- Rapid antibacterial killing at low concentrations\n- Biofilm inhibition and eradication at just 8 µg/mL\n- Synergistic enhancement of traditional antibiotics when used in combination\n- Dual mechanism: destruction of bacterial cell membrane integrity (confirmed by TEM, SEM, confocal microscopy, and flow cytometry) plus binding to bacterial DNA and RNA\n- In vivo efficacy confirmed in a mouse skin wound infection model\n- Transcriptomic analysis revealed the molecular pathways underlying its antibacterial activity","whyItMatters":"CRKP is classified as a critical-priority pathogen by the WHO because it resists nearly all available antibiotics. Infections carry mortality rates of 40-50% in some settings. Cec4's ability to kill CRKP at low concentrations, destroy biofilms (which make infections even harder to treat), and enhance existing antibiotics makes it a multi-pronged weapon against one of the most dangerous superbugs. The in vivo wound model validation moves it beyond lab curiosity toward clinical potential.","specificNumbers":"","methodology":"The researchers tested Cec4 against clinical CRKP isolates using standard antimicrobial susceptibility assays. Biofilm inhibition and eradication were quantified. Combination effects with traditional antibiotics were assessed. Membrane disruption was visualized using transmission electron microscopy, scanning electron microscopy, and confocal laser scanning microscopy. Membrane permeability was quantified by flow cytometry. DNA/RNA binding was demonstrated in vitro. In vivo efficacy was tested in a mouse skin wound infection model. Transcriptomic analysis was performed to characterize the antibacterial mechanism at the molecular level.","limitations":"The in vivo testing was limited to a skin wound infection model, which may not represent deeper tissue or bloodstream CRKP infections. Specific MIC values against the clinical isolates were not detailed in the abstract beyond the 8 µg/mL biofilm concentration. Toxicity to mammalian cells and therapeutic index were not discussed. Long-term resistance development potential was not assessed. Pharmacokinetics and systemic administration feasibility were not explored."},{"rthcId":"RPEP-12083","title":"Effect of Migraine Abortive Drugs on Benign Paroxysmal Positional Vertigo Odds: A Database Analysis.","authors":"Li, Marwin; Li, Marwin; Ceriani, Claire; Li, Hongyan","year":2025,"journal":"Audiology & neuro-otology, 30(5), 433-440","doi":"10.1159/000545977","pmid":"40349684","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12084","title":"Comparative effectiveness of GLP-1 receptor agonists and dual agonists in the treatment of patients with metabolic dysfunction associated steatohepatitis: a systematic review and meta-analysis.","authors":"Li, Meng; Hu, Jianli; Han Chin, Yip; Chew, Han Shi Jocelyn; Wang, Wenru","year":2025,"journal":"Frontiers in endocrinology, 16, 1681965","doi":"10.3389/fendo.2025.1681965","pmid":"41133230","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12085","title":"Plasma β-Endorphin and Neuropeptide Y as Candidate Biomarkers for Predicting Obstructive Sleep Apnea Syndrome: A Preliminary Study.","authors":"Li, Meng-Lin; Yang, Yi; Huang, Qian-Yun; Liu, Jian-Yong","year":2025,"journal":"Canadian respiratory journal, 2025, 4316574","doi":"10.1155/carj/4316574","pmid":"40989139","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12086","title":"Functional antimicrobial peptide-loaded 3D scaffolds for infected bone defect treatment with AI and multidimensional printing.","authors":"Li, Mengmeng; Zhao, Peizhang; Wang, Jingwen; Zhang, Xincai; Li, Jun","year":2025,"journal":"Materials horizons, 12(1), 20-36","doi":"10.1039/d4mh01124d","pmid":"39484845","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12087","title":"Novel Truncated Peptide Derived From circCDYL Exacerbates Cardiac Hypertrophy.","authors":"Li, Mengyang; Ding, Wei; Fang, Xinyu; Wang, Yu; Wang, Peiyan; Ye, Lin; Miao, Shuo; Song, Lin; Ao, Xiang; Li, Qi; Wang, Jianxun","year":2025,"journal":"Circulation research, 136(10), e94-e112","doi":"10.1161/CIRCRESAHA.124.325573","pmid":"40242872","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12088","title":"Health Technology Assessment: Evaluation of 8 CGRP-Targeted Therapy Drugs for the Treatment of Migraine.","authors":"Li, Mengyi; Huang, Siyong; Li, Jiabao; Hu, Xiao; Chen, Jisheng","year":2025,"journal":"Drug design, development and therapy, 19, 1231-1247","doi":"10.2147/DDDT.S499848","pmid":"39991088","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12089","title":"Glucagon-like peptide-1 receptor agonists for the treatment of obstructive sleep apnea: a meta-analysis.","authors":"Li, Mingxia; Lin, Hong; Yang, Qianru; Zhang, Xiaolong; Zhou, Qiong; Shi, Jiankuan; Ge, Fangfang","year":2025,"journal":"Sleep, 48(4)","doi":"10.1093/sleep/zsae280","pmid":"39626095","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12090","title":"Screening of Potential Angiotensin-Converting Enzyme-Inhibitory Peptides in Squid (Todarodes pacificus) Skin Hydrolysates: Preliminary Study of Its Mechanism of Inhibition.","authors":"Li, Mingyuan; Liang, Qianqian; Zhang, Yurui; Jiang, Xin; Gu, Yuan; Song, Xin; Wang, Xichang; Shi, Wenzheng","year":2025,"journal":"Marine drugs, 23(2)","doi":"10.3390/md23020081","pmid":"39997205","tags":[],"studyType":"in vitro + in silico","evidenceStrength":"very low","keyFinding":"Researchers screened enzymatic hydrolysates from squid (Todarodes pacificus) skin for peptides that inhibit angiotensin-converting enzyme (ACE), a key enzyme in blood pressure regulation. Using mass spectrometry (Nano LC-MS/MS) and computational analysis, they identified candidate peptides with ACE-inhibitory activity. Molecular docking studies confirmed favorable binding interactions between the identified peptides and ACE's active site. The findings establish squid skin as a viable marine source for producing blood pressure-lowering bioactive peptides.","whyItMatters":"Squid processing generates large amounts of skin waste. Identifying valuable bioactive peptides from this waste stream serves a dual purpose: creating potential natural alternatives to pharmaceutical ACE inhibitors for blood pressure management, and valorizing seafood industry byproducts. Marine-derived ACE-inhibitory peptides are of growing interest because they may offer blood pressure benefits with fewer side effects than synthetic drugs.","specificNumbers":"Squid species: Todarodes pacificus · Nano LC-MS/MS peptide identification · In silico screening + molecular docking","methodology":"Squid skin was enzymatically hydrolyzed and fractionated by molecular weight. Peptide sequences were identified using Nano LC-MS/MS tandem mass spectrometry. ACE-inhibitory potential was predicted through in silico analysis, and molecular docking simulations modeled the interactions between candidate peptides and the ACE enzyme to evaluate binding affinity and mechanism.","limitations":"This is a preliminary screening study using computational (in silico) and in vitro methods only — no animal or human studies were conducted. The abstract appears truncated, so full details of ACE inhibition potency are unclear. Computational predictions of ACE inhibition may not translate to actual biological activity. Bioavailability after oral consumption is unknown — the peptides may be degraded during digestion before reaching the bloodstream."},{"rthcId":"RPEP-12091","title":"Efficacy and safety of sacubitril/valsartan in end-stage renal disease patients with heart failure: a review.","authors":"Li, Peiyun; Li, Yupei; Zhang, Ling","year":2025,"journal":"Annals of medicine, 57(1), 2557515","doi":"10.1080/07853890.2025.2557515","pmid":"40922558","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review of clinical evidence for sacubitril/valsartan in ESRD patients with heart failure found:\n\nBenefits (particularly in patients with reduced ejection fraction):\n- Improved ventricular remodeling (reversed harmful heart enlargement)\n- Enhanced left ventricular ejection fraction (better heart pumping)\n- Reduced mortality rates\n- Reduced heart failure rehospitalization rates\n\nSafety:\n- No significant increased risk of hyperkalemia (high potassium — a major concern in dialysis patients)\n- No significant increased risk of hypotension\n- Favorable overall safety profile\n\nMechanism: Sacubitril/valsartan simultaneously regulates the RAAS (renin-angiotensin-aldosterone system) and enhances natriuretic peptide signaling, providing dual cardiovascular protection.","whyItMatters":"Dialysis patients have a cardiovascular mortality rate 10-30 times higher than the general population. Heart failure is the leading cause of death in this group, yet they've been largely excluded from the major heart failure trials that established sacubitril/valsartan's benefits. The mechanism is particularly relevant for these patients: by inhibiting neprilysin, sacubitril preserves natriuretic peptides (BNP and ANP) that help the body excrete salt and water and protect the heart — functions critically needed in patients whose kidneys can no longer perform these roles.","specificNumbers":"","methodology":"Comprehensive literature review searching PubMed, Embase, and Web of Science through December 2024 for clinical evidence on sacubitril/valsartan use in ESRD patients. The review covers pharmacological mechanisms, pharmacokinetics, and clinical outcomes data from available studies in this population, along with discussion of challenges and future directions.","limitations":"This is a narrative review, not a systematic review or meta-analysis. The available evidence in ESRD patients is limited — most sacubitril/valsartan trials excluded severe kidney disease. The studies reviewed are mostly small, observational, and heterogeneous. The drug's impact on residual kidney function in dialysis patients needs further study. Dialysis timing relative to drug dosing affects pharmacokinetics and wasn't standardized across studies."},{"rthcId":"RPEP-12092","title":"Efficient Synthesis of Cleavable Cell-Penetrating Peptide-Cargo Conjugate via Low-Equivalent of Cell-Penetrating Peptide Activated by 2,2'-Dithiodipyridine.","authors":"Li, Pincheng; Han, Xiaona; Wang, Beichen; Guo, Yanyan; Wang, Yu; Li, Yi-Ming","year":2025,"journal":"Chembiochem : a European journal of chemical biology, 26(11), e202500032","doi":"10.1002/cbic.202500032","pmid":"40200819","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12093","title":"Structural Modification and Antitumor Activity Study of Peptide Codesane: Discovery of Novel Stapled Peptide Antitumor Agents.","authors":"Li, Qingmei; Qiu, Lijuan; Li, Yong","year":2025,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 31(7), e70012","doi":"10.1002/psc.70012","pmid":"40407055","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12094","title":"Conotoxins: Classification, Prediction, and Future Directions in Bioinformatics.","authors":"Li, Rui; Yu, Junwen; Ye, Dongxin; Liu, Shanghua; Zhang, Hongqi; Lin, Hao; Feng, Juan; Deng, Kejun","year":2025,"journal":"Toxins, 17(2)","doi":"10.3390/toxins17020078","pmid":"39998095","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12095","title":"Functional Roles of Gastrin-Releasing Peptide-Producing Neurons in the Suprachiasmatic Nucleus: Insights into Photic Entrainment and Circadian Regulation.","authors":"Li, Ruoshi; Inoue, Ran; Mori, Hisashi; Hirano, Arisa; Sakurai, Takeshi","year":2025,"journal":"The Journal of neuroscience : the official journal of the Society for Neuroscience, 45(25)","doi":"10.1523/JNEUROSCI.0065-25.2025","pmid":"40404352","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12096","title":"Recent Advances in Peptide Linkers for Antibody-Drug Conjugates.","authors":"Li, Shaoting; Guo, Yu; Che, Jinxin; Dai, Haibin; Dong, Xiaowu","year":2025,"journal":"Journal of medicinal chemistry, 68(19), 19871-19892","doi":"10.1021/acs.jmedchem.5c01982","pmid":"40981705","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12097","title":"Diagnostic and prognostic value of troponins and natriuretic peptides in syncope: a systematic review and meta-analysis.","authors":"Li, Shunxiang; Liu, Jinlai; Wang, Yuanke; Lai, Donghui; Xie, Zhihui","year":2025,"journal":"Cardiovascular diagnosis and therapy, 15(5), 1032-1044","doi":"10.21037/cdt-24-485","pmid":"41216260","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12098","title":"The Effectivity MultiModality Treatment on Rehabilitation Management of Diabetic Foot Disease Patients for Improvement of Clinical Efficacy & Hemorheological Status.","authors":"Li, Shuo; Liu, Yan; Chen, Yu","year":2025,"journal":"Diabetes, metabolic syndrome and obesity : targets and therapy, 18, 2561-2571","doi":"10.2147/DMSO.S526919","pmid":"40755746","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12099","title":"Ferulic acid protects against stress-induced myocardial injury in mice.","authors":"Li, Siyong; He, Peiyi; Liu, Jiahe; Zang, Shaochuan; Luo, Jiahao; Luo, Yi; Zhu, Shuguang; Zang, Linquan","year":2025,"journal":"Toxicology and applied pharmacology, 498, 117309","doi":"10.1016/j.taap.2025.117309","pmid":"40120650","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12100","title":"Repurposing glucagon-like peptide-1 (GLP-1) receptor agonists for the treatment of depression: A systematic review of preclinical, observational and clinical investigations.","authors":"Li, Sophie; Sabbah, Sami George; Kwan, Angela T H; McIntyre, Roger S","year":2025,"journal":"European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 99, 56-67","doi":"10.1016/j.euroneuro.2025.08.002","pmid":"40925272","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 26 included studies:\n- Preclinical: 15 of 18 studies (83%) showed significant antidepressant-like effects. The mechanisms involved enhanced neuroplasticity, reduced neuroinflammation, and neurotransmitter alterations.\n- Observational: 4 of 5 studies reported reductions in depressive symptoms in human patients.\n- Clinical trials: Only 1 of 3 showed statistically significant antidepressant effects.\n\nThe disconnect between strong preclinical evidence and weak clinical trial results highlights the typical challenge of translating animal findings to human therapeutics, and suggests that more and larger clinical trials are needed before conclusions can be drawn.","whyItMatters":"Depression is a leading cause of disability worldwide, and existing antidepressants are inadequate for many patients. If GLP-1 drugs — already widely prescribed and well-characterized — could also treat depression, it would be transformative, particularly for the many patients who have both metabolic conditions and depression. The strong mechanistic evidence from animal studies provides a solid biological rationale for pursuing this further.","specificNumbers":"","methodology":"This systematic review searched MEDLINE, PubMed, and PsychINFO databases for studies investigating GLP-1 receptor agonist effects on depressive symptoms. Both animal and human studies were included. The 26 included studies were categorized as preclinical (18), observational (5), or clinical trials (3) and analyzed for evidence of antidepressant effects and underlying mechanisms.","limitations":"The clinical trial evidence is very limited (only 3 trials) and mostly negative. Animal models of depression have poor predictive validity for human outcomes. Observational studies cannot establish causation and may be confounded by weight loss, improved diabetes control, or other factors that independently affect mood. The review does not distinguish between specific GLP-1 agonists. Publication bias may inflate positive results, particularly in preclinical literature."},{"rthcId":"RPEP-12101","title":"Functional study of Bergeyella cardium KP-43 subfamily peptidases as putative T9SS cargo.","authors":"Li, Tian; Gao, Yiwen; Zhang, Xiaoyue; Zhao, Yuxiao; Hu, Fuyao; Li, Wei; Li, Lixiang; Pan, Hongwei; Zhang, Yi; Chen, Ying","year":2025,"journal":"Communications biology, 8(1), 586","doi":"10.1038/s42003-025-07996-y","pmid":"40204855","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12102","title":"Research Progress on the Mechanism of Action of Food-Derived ACE-Inhibitory Peptides.","authors":"Li, Ting; Du, Wanjia; Huang, Huiyan; Wan, Luzhang; Shang, Chenglong; Mao, Xue; Kong, Xianghui","year":2025,"journal":"Life (Basel, Switzerland), 15(8)","doi":"10.3390/life15081219","pmid":"40868867","tags":["bioactive-peptides"],"studyType":"review","evidenceStrength":"review","keyFinding":"Food-derived ACE-inhibitory peptides — obtained through natural extraction, enzymatic hydrolysis, or fermentation of foods — can block the angiotensin-converting enzyme (ACE), a key driver of high blood pressure. This review maps the landscape of these peptides: their food sources, how they're produced, their structural characteristics, and their antihypertensive activity in both lab and animal studies.\n\nThe production method significantly shapes which peptides are generated and how well they work — peptide chain length, amino acid composition, and sequence all determine ACE-inhibitory potency. Bioavailability remains a key challenge, as peptides must survive digestion to reach the bloodstream.","whyItMatters":"Hypertension affects roughly 1.3 billion people worldwide and is the leading modifiable risk factor for heart disease and stroke. Standard ACE inhibitor drugs (like lisinopril) are effective but come with side effects including persistent cough and angioedema. Food-derived ACE-inhibitory peptides could offer a natural, lower-side-effect approach to blood pressure management — either as supplements or functional foods. Understanding their mechanisms and bioavailability is essential for translating them from lab curiosity to practical health intervention.","specificNumbers":"Multiple food sources characterized · Production methods: extraction, enzymatic hydrolysis, fermentation · Structural determinants: chain length, amino acid composition, sequence · In vitro and in vivo activity data reviewed","methodology":"Systematic narrative review of published literature on food-derived ACE-inhibitory peptides, covering their sources, production methods, structural characteristics, mechanisms of action, in vitro and in vivo activity, and bioavailability.","limitations":"This is a review, not a primary study. Most evidence for food-derived ACE-inhibitory peptides comes from in vitro assays and animal studies — human clinical data is relatively limited. Lab-measured ACE inhibition doesn't always translate to real blood pressure reduction in living systems because of bioavailability challenges. The review doesn't systematically grade evidence quality across studies."},{"rthcId":"RPEP-12103","title":"Transdermal Semaglutide Administration in Mice: Reduces Body Weight by Suppressing Appetite and Enhancing Metabolic Rate.","authors":"Li, Wenjing; Cai, Ruilin; Yin, Binxin; Zhou, Yingying; Dong, Xinyuan; Li, Wenting; Wen, Jing","year":2025,"journal":"Biology, 14(5)","doi":"10.3390/biology14050575","pmid":"40427764","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12104","title":"Improving the functional performance of anthocyanin indicator films through antimicrobial peptides incorporation: Enhanced stability, swelling control, and antibacterial efficacy.","authors":"Li, Wenjun; Yang, Yuhong; Qi, Qi; Chen, Xianggui; Huang, Yukun; Chen, Hongxia; Huang, Jinhan; Chen, Pengfei","year":2025,"journal":"Food chemistry: X, 32, 103259","doi":"10.1016/j.fochx.2025.103259","pmid":"41323680","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12105","title":"Comparing Efficacy of Chiglitazar, Pioglitazone, and Semaglutide in Type 2 Diabetes: A Retrospective Study.","authors":"Li, Wenxuan; Wang, Yangang; Liu, Chuanfeng; Yu, Yongzhuo; Xu, Lili; Dong, Bingzi","year":2025,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 16(5), 993-1017","doi":"10.1007/s13300-025-01724-9","pmid":"40126828","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12106","title":"The potential biomarker value of soluble CD36 in the treatment of diabetic kidney disease: evidence from GLP-1 and insulin interventions.","authors":"Li, Wenxuan; Wang, Yangang","year":2025,"journal":"Frontiers in endocrinology, 16, 1605631","doi":"10.3389/fendo.2025.1605631","pmid":"40496556","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12107","title":"Data showing effects of resolvin D5 on prostaglandin E2 mediated inhibition of fMet-Leu-Phe induced activation of the NADPH oxidase in human neutrophils.","authors":"Li, Wenyan; Dahlgren, Claes; Forsman, Huamei","year":2025,"journal":"Data in brief, 63, 112080","doi":"10.1016/j.dib.2025.112080","pmid":"41079694","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12108","title":"Salivary Nitrate Maintains Mucosal Homeostasis via the Sialin-Neuropeptide Axis.","authors":"Li, X; Cao, Z; Chen, X; Xu, Y; Liu, H; Wang, X; Wang, J; Hu, L; Wang, S","year":2025,"journal":"Journal of dental research, 220345251362203","doi":"10.1177/00220345251362203","pmid":"40977421","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Salivary nitrate acts as a neuromodulatory signal that coordinates oral mucosal regeneration through sensory neuron activation. When nitrate was depleted (via salivary duct ligation or dietary restriction), wound healing was impaired with reduced epithelial proliferation, abnormal collagen organization, and suppressed VEGF and TGF-β expression. These deficits were rescued by nitrate supplementation.\n\nThe mechanism depends on the nitrate transporter sialin (Slc17a5): nitrate uptake through sialin promotes reinnervation of myelinated sensory nerve fibers and stimulates release of regenerative neuropeptides — calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), and neuropeptide Y. Sensory neuron-specific sialin knockout mice failed to respond to nitrate therapy, confirming sialin's essential role.","whyItMatters":"This study reveals a previously unknown mechanism connecting dietary nitrate, saliva, sensory nerves, and neuropeptide-driven tissue repair. It identifies sialin as a druggable target for enhancing wound healing and provides a mechanistic basis for why saliva accelerates oral wound repair — a phenomenon observed clinically but poorly understood at the molecular level.","specificNumbers":"","methodology":"Researchers used a palatal wound model in mice, depleting salivary nitrate through bilateral submandibular duct ligation or dietary restriction. They performed transcriptomic profiling to identify gene expression changes, used sialin knockdown in H4 cells for in vitro validation, and created sensory neuron-specific sialin knockout mice (Slc17a5ΔTrpv1) to confirm the mechanism in vivo.","limitations":"The study was conducted in mice, so the sialin-neuropeptide axis may function differently in humans. The palatal wound model represents a specific type of oral injury and may not generalize to other mucosal or tissue injuries. Specific quantitative outcomes (e.g., healing time differences, neuropeptide concentration changes) were not detailed in the abstract."},{"rthcId":"RPEP-12109","title":"Preparation and Evaluation of RGD-Conjugated Crosslinked PVA Tissue Engineered Vascular Scaffold with Endothelial Differentiation and Its Impact on Vascular Regeneration In Vivo.","authors":"Li, Xiafei; Zhang, Xuewei; Wang, Yameng; Ji, Shenglu; Zhao, Ziwei; Yin, Jianshen; Yang, Tuo; Feng, Xin; Chen, Hongli; Li, Wenbin; Wang, Xianwei; Jing, Changqin; Ding, Dan; Zhao, Liang","year":2025,"journal":"Macromolecular bioscience, 25(5), e2400554","doi":"10.1002/mabi.202400554","pmid":"39985427","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12110","title":"Overall safety evaluation of the risk signals of sacubitril/valsartan: A postmarketing pharmacoepidemiology study from 2015 to 2024.","authors":"Li, Xiangyu; Yang, Fang; Yuan, Lingjing; Dong, Tao","year":2025,"journal":"Archives of cardiovascular diseases, 118(12), 643-651","doi":"10.1016/j.acvd.2025.06.077","pmid":"40925796","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12111","title":"Digital multicriteria evaluation of negotiated medicines using Chinese mini-HTA: application of structured methodologies in assessing once-weekly GLP-1 RAs for improved clinical decision-making.","authors":"Li, Xiao; Qiu, Zhihong; Xue, Chaojun; Ren, Xiaokai; Dong, Zhanjun","year":2025,"journal":"Frontiers in pharmacology, 16, 1588056","doi":"10.3389/fphar.2025.1588056","pmid":"41041641","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide (score: 77.8) and dulaglutide (76.3) ranked highest among four once-weekly GLP-1 RAs, driven by superior HbA1c reduction and proven cardiovascular benefit. Both received \"strongly recommended\" classification. Exenatide microspheres (70.2) was also strongly recommended, primarily due to favorable cost. PEG loxenatide (62.9) received a weak recommendation due to narrower reimbursement and lower international adoption. Safety profiles were comparable across all four agents.","whyItMatters":"As GLP-1 peptide drugs become increasingly central to diabetes management globally, hospitals and health systems need rational frameworks for choosing among them. This study provides a replicable method for head-to-head comparison that goes beyond simple efficacy to include cost, policy, and practical factors — particularly relevant in markets like China where drug pricing negotiations affect availability.","specificNumbers":"","methodology":"Three-stage structured mini-health technology assessment (mini-HTA). Stage 1: Expert consensus established weighted scoring across five dimensions (pharmaceutical properties, effectiveness, safety, economy, other). Stage 2: PICO-based systematic evidence collection from guidelines, literature, and official documents. Stage 3: Quantitative scoring of each drug with classification into recommendation levels based on total scores.","limitations":"Expert consensus-based weights introduce subjectivity into the scoring system. The assessment was designed for the Chinese healthcare context, and recommendations may not apply in other regulatory and reimbursement environments. PEG loxenatide's lower score partly reflects limited international adoption rather than inherent drug deficiencies. The framework does not account for individual patient characteristics that might favor one agent over another."},{"rthcId":"RPEP-12112","title":"Perioperative management of patients on GLP-1 receptor agonists: Risks, recommendations, and future directions-A narrative review.","authors":"Li, Xiao-Yu; Jin, Yun; Feng, Xiu-Ye; Wang, Rui-Chun; Chen, Jun-Ping; Lu, Bo","year":2025,"journal":"Journal of clinical anesthesia, 104, 111871","doi":"10.1016/j.jclinane.2025.111871","pmid":"40378603","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review establishes that GLP-1 receptor agonists delay gastric emptying as a key mechanism of action, which means patients may have retained gastric contents even after standard fasting periods before surgery. This creates a risk of pulmonary aspiration during anesthesia induction.\n\nRecommendations include: careful preoperative assessment of GLP-1 RA medication details (drug type, dose, timing of last dose), pre-anesthesia gastric ultrasound to assess stomach contents, rapid sequence induction if gastric content retention is suspected, and additional monitoring during the perioperative period. The review emphasizes the need for thorough documentation of any GLP-1-related adverse events during anesthesia to build the evidence base for future guidelines.","whyItMatters":"With tens of millions of patients now taking GLP-1 drugs, every anesthesiologist and surgeon will encounter these patients regularly. The aspiration risk from delayed gastric emptying is a real and potentially life-threatening concern that wasn't part of traditional preoperative assessment. This review provides practical guidance for a rapidly evolving clinical scenario that existing anesthesia guidelines were not designed to address.","specificNumbers":"","methodology":"Narrative review of published literature on GLP-1 receptor agonist pharmacology (particularly gastric emptying effects), case reports and case series of perioperative complications, current anesthesia society guidelines, and expert recommendations for perioperative management.","limitations":"As a narrative review, the evidence synthesis may be selective. The actual incidence of clinically significant aspiration in GLP-1 RA users undergoing surgery is not well quantified — most evidence comes from case reports rather than large prospective studies. The degree of gastric emptying delay varies between different GLP-1 drugs, doses, and individual patients. The recommendations are expert consensus rather than evidence-based guidelines from randomized trials."},{"rthcId":"RPEP-12113","title":"Exendin-4 imaging based on gastrointestinal GLP-1R targets for IBD diagnosis and efficacy assessment.","authors":"Li, Xiaochen; Liu, Yang; Zhang, Zizhen; Hai, Wangxi; Pan, Yu; Zhang, Yifan","year":2025,"journal":"European journal of nuclear medicine and molecular imaging, 52(10), 3891-3902","doi":"10.1007/s00259-025-07197-z","pmid":"40178570","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12114","title":"CGRP restrains CD4+ T cell responses and allergic sensitization.","authors":"Li, Xiaoshi; Zhang, Ying; Chen, Wenlong; Meng, Qingren; Huang, Ai; Pan, Jiayi; Chen, Duan; Xiao, Yue; Wei, Jialin; Sun, Heng; Liu, Quan","year":2025,"journal":"Frontiers in immunology, 16, 1671269","doi":"10.3389/fimmu.2025.1671269","pmid":"41472747","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12115","title":"Transcriptome analysis of induced pluripotent stem cells' osteogenic differentiation reveals NPY1R activating PI3K/AKT/mTOR in alveolar bone loss during periodontitis.","authors":"Li, Xiaowen; Guo, Ruikang; Liang, Lingling; Liang, Hao; Zhou, Guangqi; Lu, Qinglan; Huang, Yonghui; Qi, Zhen; Li, Xiaojie","year":2025,"journal":"American journal of translational research, 17(10), 7749-7762","doi":"10.62347/CFCE7976","pmid":"41268237","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12116","title":"Effect of cognitive behavioral intervention on physical symptoms, B-type natriuretic peptide, red cell distribution width, C-reactive protein in elderly heart failure patients.","authors":"Li, Xiaoyan; Zhang, Meixia; Ren, Zepeng; Deng, Junfen","year":2025,"journal":"Journal of cardiothoracic surgery, 20(1), 80","doi":"10.1186/s13019-024-03315-4","pmid":"39844300","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12117","title":"Engineering Glucagon via Molecular and Formulation Strategies: From Natural Hormone to Effective and Stable Therapeutics.","authors":"Li, Xin; Wang, Yani; Chen, Zican; Tan, Zhongping","year":2025,"journal":"Chembiochem : a European journal of chemical biology, 26(22), e202500270","doi":"10.1002/cbic.202500270","pmid":"40459429","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12118","title":"Liraglutide inhibits the development of colorectal cancer by regulating TGF-β/Smad3 signaling pathway and affecting epithelial-mesenchymal transition.","authors":"Li, Xinjian; Fan, Minghu; Huang, Rong; Wang, Keqiang; Huang, Hunan","year":2025,"journal":"Discover oncology, 16(1), 1371","doi":"10.1007/s12672-025-03223-6","pmid":"40681775","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12119","title":"Cardioprotective effect of crocin in patients with breast cancer receiving anthracycline-based chemotherapy: A randomized, double-blind, placebo-controlled study.","authors":"Li, Xinye; Su, Xin; Liang, Wanping; Wang, Li; Yuan, Chao; Xu, Juping; Zhang, Yijun; Liu, Yan; Ma, Ning; Yang, Fan; Yang, Yiyuan; Tao, Liyuan; Sun, Shipeng; Shang, Hongcai; Xing, Yanwei","year":2025,"journal":"Pharmacological research, 213, 107630","doi":"10.1016/j.phrs.2025.107630","pmid":"39889867","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12120","title":"Cutaneous wound healing functions of novel milk-derived antimicrobial peptides, hLFT-68 and hLFT-309 from human lactotransferrin, and bLGB-111 from bovine β-lactoglobulin.","authors":"Li, Xixian; Zhang, Wanning; Yu, Wenhao; Yu, Yang; Cheng, Huiyuan; Lin, Yuyang; Feng, Jingwen; Zhao, Muxin; Jin, Yan","year":2025,"journal":"Scientific reports, 15(1), 9965","doi":"10.1038/s41598-025-90685-x","pmid":"40121253","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12121","title":"Serum sST2: key biomarkers in COVID-19 patients with implications for coronary artery disease.","authors":"Li, Xueqin; Tian, Yaxin; Cao, Hongyan; Cheng, Jinfang","year":2025,"journal":"BMC infectious diseases, 25(1), 471","doi":"10.1186/s12879-025-10849-y","pmid":"40197291","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"COVID-19 patients with coexisting coronary artery disease had significantly higher levels of sST2, myeloperoxidase, ALT, AST, BNP, and hs-cTnI, along with longer hospitalizations, more ICU admissions, and higher rates of heart failure and acute coronary syndrome compared to COVID-19 patients without CAD.\n\nMultivariate analysis identified sST2 as an independent risk factor for COVID-19 patients with CAD (odds ratio 1.122). sST2 correlated positively with coronary angiography Gensini score (r=0.474, p<0.001) and was significantly elevated in patients with severe coronary disease (Gensini score ≥32). ROC analysis showed sST2 predicted ICU admission, hospital stay duration, and heart failure/ACS morbidity comparably to the invasive Gensini score.","whyItMatters":"COVID-19 patients with chest symptoms need rapid assessment of whether coronary artery disease is contributing to their condition, but invasive coronary angiography isn't always feasible during acute illness. A simple blood test (sST2) that predicts coronary disease severity and clinical outcomes could help clinicians quickly identify high-risk patients and prioritize treatment — particularly valuable in resource-limited settings or when invasive procedures carry additional COVID-related risks.","specificNumbers":"","methodology":"This observational study enrolled 75 COVID-19 patients and 68 non-COVID patients admitted between December 2022 and January 2023. Demographic, laboratory (including sST2, BNP, troponin, myeloperoxidase), and clinical data were collected at admission. Coronary atherosclerosis severity was assessed using the Gensini score from coronary angiography. Patients were categorized by Gensini score and clinical characteristics. Univariate and multivariate logistic regression identified independent risk factors. ROC analysis assessed predictive performance.","limitations":"This is a single-center observational study with a relatively small sample size (143 patients). The study period was during a specific COVID-19 wave in China and may not generalize to other variants or populations. The cross-sectional design cannot establish causation between sST2 and clinical outcomes. Selection bias may exist in which patients underwent coronary angiography. Long-term follow-up and post-COVID syndrome outcomes were not assessed."},{"rthcId":"RPEP-12122","title":"Peptide-conjugated alginate fiber: A skeletal muscle regenerative scaffold.","authors":"Li, Yajun; Wu, Yueren; Wu, Tong; Zhang, Can; Dai, Jianwu; Tang, Jianping; Li, Lin; Shi, Liyang","year":2025,"journal":"Carbohydrate polymers, 354, 123299","doi":"10.1016/j.carbpol.2025.123299","pmid":"39978892","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12123","title":"Semaglultide targets Spp1+ microglia/macrophage to attenuate neuroinflammation following perioperative stroke.","authors":"Li, Yan; Fan, Qiuyue; Pang, Rui; Cai, Ling; Qi, Jie; Chen, Weijie; Zhang, Yueman; Chen, Chen; Yu, Weifeng; Li, Peiying","year":2025,"journal":"Journal of neuroinflammation, 22(1), 143","doi":"10.1186/s12974-025-03465-9","pmid":"40426210","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Single-cell RNA sequencing in a perioperative ischemic stroke (PIS) mouse model identified a novel Spp1+ macrophage/microglia subgroup with enriched anti-inflammatory pathways and distinct lipid metabolic reprogramming. These cells express GLP-1 receptors, confirmed by immunofluorescence.\n\nSemaglutide treatment resulted in:\n- Significant reduction in cerebral infarct volume in PIS mice compared to ischemic stroke alone\n- Increased proportion of Spp1+Edu+Iba-1+ cells (proliferating protective microglia) at 3 days post-PIS\n- Significant attenuation of neuroinflammatory markers\n- Significant improvement in sensorimotor function within 3 days\n\nThese findings reveal a novel protective immune cell subset and demonstrate it can be therapeutically expanded by semaglutide.","whyItMatters":"Perioperative stroke is a feared surgical complication with limited treatment options. Surgery itself worsens stroke outcomes through neuroinflammation, creating a worse situation than a stroke happening outside the surgical context. This study identifies both a new protective immune mechanism and a way to enhance it with an existing drug. If semaglutide can reduce perioperative stroke damage, it could benefit the millions of patients who undergo surgery and are at risk for this complication.","specificNumbers":"","methodology":"Researchers used a perioperative ischemic stroke mouse model combining surgery with brain ischemia. Single-cell RNA sequencing was used to characterize immune cell populations in the ischemic brain. GLP-1 receptor expression on Spp1+ cells was confirmed by immunofluorescence. Semaglutide was administered intraperitoneally. Outcomes were assessed using infarct volume measurement, high-parameter flow cytometry, immunofluorescence staining, RNA sequencing, and sensorimotor behavioral testing.","limitations":"This is a preclinical study in mice that may not translate directly to human perioperative stroke. The perioperative stroke model combines surgery with experimental ischemia, which may differ from how strokes actually occur in surgical patients. Semaglutide was given as prevention/early treatment — its effectiveness when given after stroke onset is unknown. The 3-day follow-up is short and doesn't assess long-term outcomes. Specific semaglutide doses used may not correspond to human clinical doses."},{"rthcId":"RPEP-12124","title":"BroadAMP-GPT: AI-Driven generation of broad-spectrum antimicrobial peptides for combating multidrug-resistant ESKAPE pathogens.","authors":"Li, Yanru; Xu, Xianghan; Zhang, Xiaohui; Xu, Zhihui; Zhao, Jiaqi; Zhu, Ruiyu; Wang, Ziyu; Ran, Wei; Zhao, Wenqian; Yan, Ningyang; Leng, Yifan; Miao, Zexu; Wang, Xiaomin; Wang, Liping; Liu, Jinxin; Pian, Cong; Huang, Jinhu","year":2025,"journal":"Gut microbes, 17(1), 2523811","doi":"10.1080/19490976.2025.2523811","pmid":"40568788","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12125","title":"Emerging therapeutic potential of glucagon-like Peptide-1 receptor agonists in knee osteoarthritis: a systematic review.","authors":"Li, Yapeng; Yang, Lanbo; Li, Feng; Fu, Jia; Zhao, Wangyu; Wu, Xiaolong; Guo, Jiayi; Yue, Chen","year":2025,"journal":"Frontiers in pharmacology, 16, 1627691","doi":"10.3389/fphar.2025.1627691","pmid":"41158135","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12126","title":"Meta-analysis of the Effect of Semaglutide on Blood Pressure in Obese Populations.","authors":"Li, Yihan; Xue, Kefan; Hu, Rui; Hu, Xiao; Guo, Ran; Guo, Hongxia; Li, Gang","year":2025,"journal":"American journal of cardiovascular drugs : drugs, devices, and other interventions, 25(5), 655-665","doi":"10.1007/s40256-025-00738-9","pmid":"40493329","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 22 RCTs (15,347 participants), semaglutide significantly reduced systolic blood pressure (MD -2.90 mmHg, 95% CI -3.70 to -2.11, P<0.01) and diastolic blood pressure (MD -0.86 mmHg, 95% CI -1.34 to -0.38, P<0.01). Subgroup analysis: non-diabetic populations showed greater reductions (SBP -5.02 mmHg, DBP -1.96 mmHg) versus diabetic populations (SBP -1.87 mmHg, DBP -0.43 mmHg). Higher dose (2.4 mg) significantly lowered SBP by 4.31 mmHg and DBP by 1.84 mmHg. Sensitivity analysis confirmed robust results.","whyItMatters":"Hypertension is the leading modifiable risk factor for cardiovascular disease and stroke. Finding that semaglutide reduces blood pressure — especially at the higher 2.4 mg obesity dose — adds another reason to prescribe it for obese patients who often have multiple cardiovascular risk factors. The greater effect in non-diabetic populations suggests the blood pressure benefit isn't just from improved metabolic health but may involve direct cardiovascular mechanisms.","specificNumbers":"","methodology":"Systematic review and meta-analysis of randomized controlled trials searching PubMed, Embase, Cochrane Library, and Web of Science through October 2024. Included 22 studies with 15,347 participants evaluating semaglutide's effect on blood pressure in obese populations. Statistical analysis used Stata with mean differences and 95% confidence intervals. Subgroup analyses by diabetes status and semaglutide dose. Egger's test assessed publication bias. Sensitivity analysis evaluated result stability.","limitations":"Heterogeneity was present in some subgroup analyses, particularly at the 2.4 mg dose level. The blood pressure reductions, while statistically significant, are modest in absolute terms (2.9 mmHg systolic). Whether these reductions are independent of weight loss is unclear — weight reduction alone would be expected to lower blood pressure. The meta-analysis combined studies with different durations, populations, and semaglutide formulations (subcutaneous and oral). Individual patient data were not available for more granular subgroup analyses."},{"rthcId":"RPEP-12127","title":"Puerarin Reversing Autophagy-Lysosomal Dysfunction via Acid Sphingomyelinase Inhibition in Cardiomyocytes.","authors":"Li, Yin-Ping; He, Qian; Yu, Xiao-Ying; Xiong, Sheng-Tao; You, Hong-Jing; Xuan, Yue; Liao, Wei-Yan; Chen, Ze-Yu; Li, Hai-Yan; Wang, Wei; Chen, Yang; Wang, Xiao","year":2025,"journal":"Journal of cellular and molecular medicine, 29(4), e70427","doi":"10.1111/jcmm.70427","pmid":"39993967","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12128","title":"Decoding the neuroimmune axis in colorectal cancer: From neural circuitry to therapeutic innovation.","authors":"Li, Ying; Yang, Sheng-Ya; Zhang, Ying-Ru; Wang, Yan","year":2025,"journal":"Cytokine & growth factor reviews, 83, 3-17","doi":"10.1016/j.cytogfr.2025.04.001","pmid":"40274426","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review systematically catalogs how three major neuropeptides influence colorectal cancer immunity:\n\n1. **Substance P** — modulates immune cell recruitment and inflammatory responses in the tumor microenvironment\n2. **Calcitonin gene-related peptide (CGRP)** — influences immune cell function and may affect how the tumor evades immune surveillance\n3. **Vasoactive intestinal peptide (VIP)** — has immunomodulatory effects that can reshape the tumor's immune landscape\n\nThese neuropeptides, along with neurotransmitters and neurotrophic factors, form a complex neuroimmune axis that significantly impacts colorectal cancer progression and the tumor's ability to escape immune destruction.","whyItMatters":"Colorectal cancer is one of the most common cancers worldwide, and immunotherapy has shown limited success for many CRC patients. The neuroimmune axis represents an underexplored dimension of cancer biology. If neuropeptides are actively reshaping tumor immunity, then targeting or manipulating these peptides could enhance immunotherapy effectiveness or provide entirely new treatment strategies for CRC.","specificNumbers":"","methodology":"This is a comprehensive narrative review that systematically synthesizes published research on the neuroimmune axis in colorectal cancer. The authors categorized neuroregulatory mediators into neurotransmitters, neuropeptides, and neurotrophic factors, and evaluated their immunomodulatory effects in the context of CRC pathogenesis and tumor immunity remodeling.","limitations":"As a review, this paper does not present new experimental data. Much of the evidence for neuropeptide effects on tumor immunity comes from in vitro and animal studies, with limited clinical validation in human CRC patients. The complex, context-dependent nature of neuropeptide signaling (sometimes pro-tumor, sometimes anti-tumor) makes therapeutic targeting challenging. The review also acknowledges that translational prospects face significant hurdles."},{"rthcId":"RPEP-12129","title":"Cardiac Indices Parameters on the Ultrasonic Cardiac Output Monitor as Potential Indicators to Predict the Ultrafiltration Endpoint Success in Acute Heart Failure Treatment.","authors":"Li, Yiou; Chen, Jiajia; Bian, Jianye; Chen, Fangyuan; Wan, Qianli; Yuan, Fang","year":2025,"journal":"Reviews in cardiovascular medicine, 26(5), 27100","doi":"10.31083/RCM27100","pmid":"40475748","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12130","title":"Chitosan based surface modulation of core-shell nanoparticles for oral delivery of exenatide via balancing mucus penetration and cellular uptake.","authors":"Li, Yiyao; Tian, Huixian; Zeng, Han; Zhang, Yu; Yin, Tian; He, Haibing; Gou, Jingxin; Tang, Xing","year":2025,"journal":"International journal of pharmaceutics, 672, 125319","doi":"10.1016/j.ijpharm.2025.125319","pmid":"39921014","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Chitosan-coated EDB nanoparticles (CS-EDB NPs) achieved 83.5% exenatide encapsulation efficiency, ~277 nm particle size, and -16.2 mV zeta potential. Compared to uncoated NPs, the chitosan coating reduced mucus penetration by 1.1-fold but increased cellular uptake by 2.15-fold and transepithelial transport by 1.77-fold. Uptake was primarily energy-dependent endocytosis with partial macropinocytosis. The NPs achieved 13.29% pharmacological bioavailability and effectively regulated blood glucose, serum lipids, and improved islet function with long-term oral administration.","whyItMatters":"Oral delivery of peptide drugs is one of the biggest challenges in pharmaceutical science. Most approaches achieve less than 5% bioavailability. Achieving 13.29% with exenatide is a significant accomplishment. If this technology can be scaled and translated to humans, it could eliminate injections for GLP-1 therapy — a major barrier to patient compliance, especially considering the millions of people now taking these drugs for diabetes and obesity.","specificNumbers":"","methodology":"Double emulsification combined with interfacial crosslinking to create EXT-loaded core-shell nanoparticles coated with chitosan. Mucus penetration measured using Transwell model. Cellular uptake and transepithelial transport tested in Caco-2/E-12 co-culture model. Pharmacological bioavailability and metabolic outcomes measured in vivo (animal species not specified in abstract but mesh terms indicate rats).","limitations":"The 13.29% bioavailability, while impressive for oral peptides, still means nearly 87% of the drug is lost. The study used cell culture models and animal testing — human gut physiology differs significantly. Chitosan nanoparticle manufacturing at pharmaceutical scale presents challenges. Long-term stability and cost-effectiveness haven't been addressed."},{"rthcId":"RPEP-12131","title":"Liraglutide use in pediatric type 2 familial partial lipodystrophy caused by LMNA mutation: a case report.","authors":"Li, Youran; Yu, Ronghua; Song, Ting; Xiao, Yongmei; Xu, Wuhen; Zhang, Ting; Li, Xiaolu","year":2025,"journal":"BMC pediatrics, 25(1), 537","doi":"10.1186/s12887-025-05886-0","pmid":"40619352","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12132","title":"Liraglutide modulates lipid metabolism via ZBTB20-LPL pathway.","authors":"Li, Yue; Gao, Rui; Yang, Zhiyan; Zong, Huiying; Li, Yan","year":2025,"journal":"Life sciences, 360, 123267","doi":"10.1016/j.lfs.2024.123267","pmid":"39608448","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Liraglutide regulates lipid metabolism through a newly identified ZBTB20-LPL pathway:\n\n**In vitro (3T3-L1 adipocytes):**\n- Reduced lipid droplets and triglyceride (TG) levels\n- Altered expression of genes involved in fatty acid metabolism, lipogenesis, fatty acid oxidation, and adipocyte browning\n- Downregulated ZBTB20, a transcriptional suppressor\n- ZBTB20 overexpression confirmed it inhibits LPL (lipoprotein lipase) expression\n\n**In vivo (ob/ob obese mice, 4 weeks):**\n- Improved blood lipid levels\n- Reduced adipose tissue volume and adipocyte size\n- Confirmed ZBTB20-LPL pathway regulation in adipose tissue\n\nThis establishes a molecular mechanism: liraglutide → reduced ZBTB20 → increased LPL → enhanced lipid breakdown.","whyItMatters":"While liraglutide is widely prescribed for diabetes and weight loss, understanding its specific molecular mechanisms for fat reduction helps explain why it works and could guide the development of more targeted therapies. The ZBTB20-LPL pathway is a novel finding that adds to our understanding of GLP-1 drug biology and could identify new drug targets for lipid disorders.","specificNumbers":"","methodology":"In vitro: 3T3-L1 preadipocytes were differentiated into adipocytes and treated with liraglutide. RNA sequencing identified differentially expressed genes, with GO and KEGG enrichment analyses pinpointing lipid regulation targets. Lentiviral overexpression of Zbtb20 validated its role. In vivo: ob/ob mice received subcutaneous liraglutide or saline for 4 weeks. Outcomes included blood lipids, adipose tissue volume, adipocyte size, and target gene expression via immunohistochemistry and RT-qPCR.","limitations":"The study used an established cell line (3T3-L1) and a genetic obesity mouse model (ob/ob), which may not perfectly represent human adipose tissue biology. The 4-week in vivo treatment period is relatively short. The study focused on one pathway (ZBTB20-LPL), but liraglutide likely affects lipid metabolism through multiple mechanisms simultaneously. Whether the ZBTB20-LPL pathway is the primary driver of liraglutide's lipid effects in humans remains to be determined."},{"rthcId":"RPEP-12133","title":"Plasmacytoid dendritic cells alleviate allergic asthma via airway epithelial cell-dependent thymosin β4 expression.","authors":"Li, Yue; Chen, Zhengrong; Han, Miaomiao; Duan, Zhen; Li, Ruizhe; Cui, Xinyi; Ge, Haiyan; Shu, Yilai; Li, Huabin; He, Rui","year":2025,"journal":"The Journal of allergy and clinical immunology, 156(1), 171-185","doi":"10.1016/j.jaci.2025.01.047","pmid":"39978686","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12134","title":"Tirzepatide, a dual GIP/GLP-1 receptor agonist, alleviates metabolic dysfunction-associated steatotic liver disease by reducing the expression of CD36 and OBP2A.","authors":"Li, Yun; Sun, Wencong; Liu, Hong; Ruan, Xiong Z","year":2025,"journal":"Genes & diseases, 12(6), 101761","doi":"10.1016/j.gendis.2025.101761","pmid":"40837406","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12135","title":"Mechanisms of efficacy of drug therapy in type 2 diabetes: the role of microbiomes.","authors":"Li, Yushan; He, Ziling; Li, Chunyan; Huang, Jing; Yu, Zheng","year":2025,"journal":"Minerva endocrinology","doi":"10.23736/S2724-6507.25.04306-4","pmid":"40587084","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 receptor agonists (semaglutide, liraglutide), metformin, SGLT-2 inhibitors (dapagliflozin), and berberine all interact with gut microbiota to exert therapeutic effects in type 2 diabetes. Each drug modulates metabolic homeostasis, immune response, and gut barrier function through microbiome changes. Notably, each drug can have conflicting effects on gut flora depending on timing and mode of administration. The gut microbiota may also impact drug safety profiles, suggesting bidirectional drug-microbiome interactions.","whyItMatters":"GLP-1 receptor agonists are among the most prescribed medications globally, yet we're still discovering how they work. The gut microbiome connection suggests these peptide drugs have effects beyond direct receptor activation — they reshape the gut ecosystem in ways that contribute to blood sugar control, weight loss, and potentially other benefits. This knowledge could optimize how and when these drugs are prescribed.","specificNumbers":"","methodology":"Narrative literature review selecting representative glucose-lowering drugs (metformin, dapagliflozin, semaglutide, liraglutide, and berberine) and summarizing evidence for their interactions with gut microbiota in type 2 diabetes treatment.","limitations":"This is a narrative review, not a systematic review, so it may not comprehensively cover all relevant studies. Much of the evidence for drug-microbiome interactions comes from animal studies that may not translate to humans. The mechanisms described are largely associative rather than causal. The review combines very different drug classes, making direct comparisons difficult. Individual variation in gut microbiota composition is not adequately addressed."},{"rthcId":"RPEP-12136","title":"In silico identification and experimental validation of two types of angiotensin-converting enzyme (ACE) and xanthine oxidase (XO) milk inhibitory peptides.","authors":"Li, Zekun; Zhang, Wenhua; Abubaker, Mohamed Aamer; Shu, Qin; Liu, Yongfeng","year":2025,"journal":"Food chemistry, 464(Pt 3), 141864","doi":"10.1016/j.foodchem.2024.141864","pmid":"39504900","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12137","title":"Association Between Markers of Atrial Cardiopathy and Cognitive Impairment Risk Among Adults with No Suggestive History of Atrial Fibrillation.","authors":"Li, Zhe; Marion, Danielle; Blair, Jessica; Soliman, Elsayed Z; Gladstone, David; Kamel, Hooman; Birnie, David; Manuel, Doug; Unverzagt, Frederick W; Howard, Virginia J; Edwards, Jodi D","year":2025,"journal":"CJC open, 7(12), 1539-1548","doi":"10.1016/j.cjco.2025.07.010","pmid":"41542129","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12138","title":"Markers of left atrial cardiopathy and cognitive function trajectories in adults aged ≥45 years without atrial fibrillation: a population-based study.","authors":"Li, Zhe; Marion, Danielle; Blair, Jessica; Soliman, Elsayed Z; Gladstone, David; Kamel, Hooman; Birnie, David; Manuel, Doug; Unverzagt, Frederick W; Howard, Virginia; Edwards, Jodi D","year":2025,"journal":"Research square","doi":"10.21203/rs.3.rs-6872566/v1","pmid":"40894023","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12139","title":"Potential application of mono-, dual-, and triple-target GLP-1 receptor agonists in improving the prognosis of patients with diabetic foot ulcers.","authors":"Li, Zhe; Wang, Xujing; He, Yan; Hu, Keyan; Liu, Yanyun; Zhang, Weiguang; Ma, Yujin; Jiang, Hongwei","year":2025,"journal":"Frontiers in endocrinology, 16, 1754925","doi":"10.3389/fendo.2025.1754925","pmid":"41647111","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12140","title":"Engineering a nano-drug delivery system to regulate m6A modification and enhance immunotherapy in gastric cancer.","authors":"Li, Zhengshuo; Zhang, Xiaoyue; Liu, Can; Wu, Yangge; Wen, Yuqing; Zheng, Run; Xu, Chenxiao; Tian, Junrui; Peng, Qiu; Zheng, Xiang; Wang, Jia; Yan, Qun; Wei, Lingyu; Ma, Jian","year":2025,"journal":"Acta biomaterialia, 191, 412-427","doi":"10.1016/j.actbio.2024.11.036","pmid":"39581334","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12141","title":"Oral-Delivery Lactococcus lactis expressing cherry fusion lactoferrin peptides against infection of avian pathogenic Escherichia coli in chickens.","authors":"Li, Zhuoran; Wang, Xueying; Zheng, Dianzhong; Han, Fuzhen; Li, Yue; Zhou, Han; Li, Jiaxuan; Cui, Wen; Jiang, Yanping; Wang, Xiaona; Xie, Weichun; Tang, Lijie","year":2025,"journal":"Poultry science, 104(1), 104637","doi":"10.1016/j.psj.2024.104637","pmid":"39662258","tags":[],"studyType":"animal","evidenceStrength":"preliminary","keyFinding":"Researchers engineered a probiotic bacterium (Lactococcus lactis) to produce lactoferrin antimicrobial peptides (lactoferricin and lactoferrampin) and fed it to chickens. The engineered probiotic inhibited pathogenic E. coli (APEC-O78) and Staphylococcus aureus in vitro, and when added to chicken feed it improved growth performance, boosted immune markers (serum IgG, intestinal SIgA), suppressed pro-inflammatory cytokines (IL-1β, IL-12, IFN-γ, TNF-α), and restored gut microbiome balance disrupted by infection.\n\nThe construct was designed without antibiotic resistance genes and included a fluorescent marker for tracking — addressing safety concerns about engineered probiotics entering the food chain.","whyItMatters":"Antibiotic-resistant bacteria from livestock can spread to humans through food and the environment. Replacing antibiotics with antimicrobial peptide-producing probiotics could break this transmission cycle. This study demonstrates a practical delivery system — engineering food-grade bacteria to continuously produce antimicrobial peptides in the gut — that could reduce antibiotic use in the poultry industry while maintaining animal health.","specificNumbers":"Inhibited APEC-O78 and S. aureus in vitro · Increased serum IgG and intestinal SIgA · Suppressed IL-1β, IL-12, IFN-γ, TNF-α · Improved average daily intake and gain-to-feed ratio · Restored gut microbiome (16S rDNA) · No antibiotic resistance genes","methodology":"Researchers constructed a recombinant L. lactis MG1363 strain expressing bovine lactoferricin and lactoferrampin peptides with an mCherry fluorescent marker and no antibiotic resistance gene. In vitro antimicrobial activity was tested against APEC-O78 and S. aureus. Chickens were fed the engineered probiotic and then challenged with APEC-O78. Outcomes measured included growth performance, serum IgG, intestinal SIgA, inflammatory cytokines, and gut microbiome composition via 16S rDNA sequencing.","limitations":"This is a poultry study — results may not translate directly to mammalian or human applications of lactoferrin peptides. The specific number of chickens and statistical details were not provided in the abstract. Long-term safety of feeding engineered probiotics to food animals and potential environmental release are not addressed. The applicability to human gut health is indirect."},{"rthcId":"RPEP-12142","title":"Long-Term Efficacy Trajectories of GLP-1 Receptor Agonists: A Systematic Review and Network Meta-Analysis.","authors":"Li, Zixuan; Han, Zhoubo; Sun, Rong; Xuan, Xiuping; Huang, Chenghu","year":2025,"journal":"Diabetes, metabolic syndrome and obesity : targets and therapy, 18, 3611-3624","doi":"10.2147/DMSO.S539822","pmid":"41019499","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12143","title":"Integrated strategy for biotransformation of antibody-drug conjugates and multidimensional interpretation via high-resolution mass spectrometry.","authors":"Li, Ziyi; Zhang, Jingxian; Wu, Yue; Wang, Fan; Cai, Tingting","year":2025,"journal":"Drug metabolism and disposition: the biological fate of chemicals, 53(6), 100081","doi":"10.1016/j.dmd.2025.100081","pmid":"40354712","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12144","title":"Intestinal bitter taste receptors in health: a multifactorially regulated role from the perspective of metabolic crosstalk.","authors":"Liang, Jiafan; Chen, Jiahui; Zhao, Guoping; Wang, Yanbo","year":2025,"journal":"Critical reviews in food science and nutrition, 1-13","doi":"10.1080/10408398.2025.2563176","pmid":"40996059","tags":["glp-1","gut-peptides"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Bitter taste receptors (TAS2Rs) in the intestines do far more than detect bitter flavors — they regulate the release of gut hormones like GLP-1, control gastric emptying, and influence appetite, satiety, and energy balance. This review reveals that TAS2Rs interact with other taste receptors in the gut through shared signaling pathways, creating a complex network that affects metabolic health and disease progression.\n\nTAS2R expression is influenced by genetics, gut microbiome composition, age, and sex. Environmental chemicals can also alter TAS2R expression, potentially contributing to metabolic disorders. The review positions TAS2Rs as promising therapeutic targets but warns that any intervention must account for the intricate crosstalk between different taste receptor systems in the gut.","whyItMatters":"The discovery that bitter taste receptors in your gut help control GLP-1 release — the same hormone targeted by blockbuster drugs like semaglutide — opens an entirely different approach to metabolic disease. Instead of injecting GLP-1 analogs, it may eventually be possible to stimulate the body's own GLP-1 production by activating intestinal bitter taste receptors through diet or targeted compounds. This review maps the complexity of that system and what must be understood before such therapies can be developed.","specificNumbers":"TAS2R family of receptors · GLP-1 hormone regulation · Influenced by genetics, gut microbiome, age, sex · Shared signaling pathways with other taste receptors","methodology":"This is a narrative review published in Critical Reviews in Food Science and Nutrition. The authors synthesized published research on intestinal bitter taste receptors, their role in gut hormone signaling, interactions with other taste receptors, and factors influencing their expression. The review covers molecular signaling, metabolic effects, and regulatory influences from genetics to the microbiome.","limitations":"As a review article, no new experimental data is presented. Much of the evidence linking TAS2Rs to metabolic outcomes comes from cell culture and animal studies — human clinical data is limited. The precise therapeutic potential of targeting TAS2Rs remains speculative. The interactions between different taste receptor systems are described conceptually but not fully quantified."},{"rthcId":"RPEP-12145","title":"Exploring the molecular mechanisms of tirzepatide in alleviating metabolic dysfunction-associated fatty liver in mice through integration of metabolomics, lipidomics, and proteomics.","authors":"Liang, Jinliang; Liu, Huanyi; Lv, Guo; Chen, Xiaotong; Yang, Zhaoshou; Hu, Kunhua; Sun, Hongyan","year":2025,"journal":"Lipids in health and disease, 24(1), 8","doi":"10.1186/s12944-024-02416-2","pmid":"39794823","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12146","title":"Heyndrickxia coagulans spore-based nanoparticle generator for improved oral insulin delivery and hypoglycemic therapy.","authors":"Liang, Jinying; Bai, Mengxin; Bi, Yarong; Jian, Xiangjie; Wang, Siyan; Jiang, Shang; Zhao, Ying; Ma, Weiwei; Yin, Shaoping; Zhang, Wenli","year":2025,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 378, 103-115","doi":"10.1016/j.jconrel.2024.12.008","pmid":"39657890","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12147","title":"Exploration of ACE inhibitory peptides from sea cucumber viscera with DPP-IV inhibitory activity: Virtual screening, characterization, and potential mechanism investigation.","authors":"Liang, Qingping; Zhou, Wei; Peng, Siyuan; Liang, Ziyu; Liu, Zhemin; Wang, Linbin; Mukhtar, Hina; Mou, Haijin","year":2025,"journal":"International journal of biological macromolecules, 311(Pt 3), 143843","doi":"10.1016/j.ijbiomac.2025.143843","pmid":"40318712","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12148","title":"Heterologous expression of a recombinant ACE inhibitory peptide LYPVK and its potential antihypertensive action mechanism.","authors":"Liang, Qingping; Liu, Zhemin; Xu, Menghao; Zhu, Jihai; Liang, Ziyu; Zhu, Changliang; Mou, Haijin","year":2025,"journal":"International journal of biological macromolecules, 300, 140274","doi":"10.1016/j.ijbiomac.2025.140274","pmid":"39863209","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12149","title":"Mining for Novel Umami Peptides from Sea Cucumber Viscera Hydrolysate with ACE Inhibitory Activity.","authors":"Liang, Qingping; Zhong, Yiling; Ren, Xinmiao; Liang, Ziyu; Zhu, Changliang; Wang, Linbin; Mou, Haijin","year":2025,"journal":"Journal of agricultural and food chemistry, 73(25), 15751-15766","doi":"10.1021/acs.jafc.5c04439","pmid":"40500286","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12150","title":"Rational module substitution strategy to enhance ACE-inhibitory peptide activity.","authors":"Liang, Qingping; Peng, Siyuan; Liu, Zhemin; Wang, Jia; Tang, Luying; Zhu, Changliang; Zhu, Lin; Yang, Min; Li, Dongyu; Mou, Haijin","year":2025,"journal":"Food chemistry, 494, 146191","doi":"10.1016/j.foodchem.2025.146191","pmid":"40907193","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12151","title":"Human neutrophil α-defensin HNP1 interacts with bacterial OmpA to promote Acinetobacter baumannii biofilm formation.","authors":"Liao, Chongbing; Liu, Qihui; Luo, Gan; Luo, Yinyue; Yao, Dan; Wang, Qingxia; Zhang, Jue; Wu, Yang; Jin, Jialin; Xu, Dan; Lu, Wuyuan","year":2025,"journal":"Nature communications, 16(1), 5629","doi":"10.1038/s41467-025-60935-7","pmid":"40595622","tags":[],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"The human antimicrobial peptide HNP1 (human neutrophil α-defensin 1) — normally part of the body's immune defense — paradoxically promotes biofilm formation by the dangerous hospital-acquired pathogen Acinetobacter baumannii. HNP1 was found in the lung fluid of infected patients and interacts with the bacterial outer membrane protein OmpA to enhance biofilm production.\n\nAs a result of this HNP1-enhanced biofilm, A. baumannii becomes more tolerant to antibiotics and more effectively colonizes host cells and tissues. This represents a striking example of a pathogen co-opting a host defense peptide for its own benefit.","whyItMatters":"This finding flips the traditional narrative about defensins as purely protective molecules. It reveals that A. baumannii has evolved to exploit the very immune peptides sent to destroy it, using HNP1 to build biofilms that increase antibiotic resistance. This has implications for understanding treatment failure in hospital-acquired infections and could redirect strategies for combating multidrug-resistant A. baumannii.","specificNumbers":"","methodology":"Researchers analyzed bronchoalveolar lavage fluids from A. baumannii-infected patients to confirm HNP1 presence. They then conducted in vitro experiments to characterize the interaction between HNP1 and the bacterial outer membrane protein OmpA, and assessed the downstream effects on biofilm formation, antibiotic tolerance, and host cell colonization.","limitations":"While HNP1 was confirmed present in patient lung fluid, the biofilm formation mechanism was primarily characterized in vitro. The clinical significance of HNP1-promoted biofilm in actual patient outcomes needs further investigation. The study focused on the HNP1-OmpA interaction specifically and may not capture other defensin-bacterial interactions."},{"rthcId":"RPEP-12152","title":"Trigeminal nerve root compression induced neuroinflammatory response promotes mechanical allodynia through the CGRP/SP-Piezo2 axis via Ca2+ signaling.","authors":"Liao, Xinyue; Luo, Zhaoke; Huang, Feng; Wang, Yiqian; Zeng, Zhangying; Liao, Weihang; Ou, Yating; Wu, Xuemei; Wang, Feng; Luo, Daoshu","year":2025,"journal":"Cellular & molecular biology letters, 31(1), 3","doi":"10.1186/s11658-025-00831-6","pmid":"41340091","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12153","title":"Co-delivery of antimicrobial peptide and Prussian blue nanoparticles by chitosan/polyvinyl alcohol hydrogels.","authors":"Liao, Zhiyi; Li, Jiayi; Ni, Wenqiang; Zhan, Rixing; Xu, Xisheng","year":2025,"journal":"Carbohydrate polymers, 348(Pt A), 122873","doi":"10.1016/j.carbpol.2024.122873","pmid":"39562133","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The MSI-1 antimicrobial peptide was covalently attached to a chitosan/polyvinyl alcohol hydrogel containing Prussian blue nanoparticles (PBNPs). The dual-mode system demonstrated:\n\n- Sustained bactericidal activity against S. aureus and E. coli for 24 hours through the antimicrobial peptide surface\n- Photothermal heating to 48.3°C within 10 minutes under 808 nm near-infrared light, sufficient to disrupt bacterial biofilms\n- Over 90% cell survival in co-culture for 3 days, indicating biocompatibility\n- No damage to major organs in animal experiments\n\nThe mild photothermal temperature avoids thermal damage to healthy tissue while still being effective against biofilms.","whyItMatters":"Infected wounds are a major healthcare problem, especially as antibiotic resistance grows. Biofilm formation makes infections even harder to treat. This dressing attacks the problem from two angles — an antimicrobial peptide for killing individual bacteria and photothermal treatment for disrupting the protective biofilm structures that make infections chronic.","specificNumbers":"","methodology":"The antimicrobial peptide MSI-1 was covalently linked to chitosan-modified PVA hydrogels through amine-carboxyl coupling. Prussian blue nanoparticles were incorporated for photothermal capability. Antimicrobial activity was tested against S. aureus and E. coli. Photothermal performance was characterized under 808 nm NIR light. Biocompatibility was assessed through cell co-culture and animal organ toxicity studies.","limitations":"In vitro and animal testing only — human clinical trials have not been conducted. The photothermal component requires an external NIR light source, adding complexity to clinical use. Only two bacterial species were tested. Long-term stability and shelf life of the peptide-loaded hydrogel were not assessed. The 48.3°C photothermal temperature needs careful control to avoid tissue damage in clinical settings."},{"rthcId":"RPEP-12154","title":"Fatty Liver Disease in the Diabetic Population: A Cross-Sectional Study From Pakistan.","authors":"Liaquat Memon, Hassan; Farooq, Shafaq; Aslam, Muhammad; Hyder, Ali; Tareen, Khaild; Ahmed, Imran; Khan, Raja Taha Yaseen","year":2025,"journal":"Cureus, 17(6), e85510","doi":"10.7759/cureus.85510","pmid":"40630376","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12155","title":"Semaglutide Decreases Risk of Non-Arteritic Anterior Ischemic Optic Neuroapthy in Type 2 Diabetic Patients.","authors":"Lieberman, Rachel A; Korona-Bailey, Jessica; Banaag, Amanda; Furhman, Barbara; Corrado, Richele; Koehlmoos, Tracey Perez","year":2025,"journal":"Military medicine","doi":"10.1093/milmed/usaf522","pmid":"41217382","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12156","title":"Functional Assessment of Genetically Modified Infrapatellar Fat Pad Mesenchymal Stem/Stromal Cell-Derived Extracellular Vesicles (EVs): Potential Implications for Inflammation/Pain Reversal in Osteoarthritis.","authors":"Liebmann, Kevin; Castillo, Mario; Jergova, Stanislava; Rahimi, Behnaz; Kaplan, Lee D; Best, Thomas M; Sagen, Jacqueline; Kouroupis, Dimitrios","year":2025,"journal":"Cells, 14(24)","doi":"10.3390/cells14241952","pmid":"41439971","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Extracellular vesicles from stem cells engineered with the CGRP antagonist peptide CGRP8-37 showed multimodal therapeutic effects in osteoarthritis. In vitro, the EVs downregulated inflammatory markers (TNF, TLR4, MAPK8) in nerve cells and promoted cartilage-building gene expression. In vivo (mouse model), intra-articular injection reduced pain behaviors, preserved cartilage structure, restored stem/progenitor cell localization, and trended toward reducing Substance P levels. The EVs carried anti-inflammatory miRNAs, proteins including neprilysin (which degrades the pain peptide Substance P), and 11 long non-coding RNAs linked to joint homeostasis.","whyItMatters":"Osteoarthritis affects over 500 million people and current treatments only manage symptoms. This cell-free approach targets both the pain (via CGRP and Substance P neuropeptide pathways) and the structural damage simultaneously — something current OA drugs cannot do. It represents a potential disease-modifying therapy rather than just symptom relief.","specificNumbers":"500 million people affected by OA globally · CGRP8-37 antagonist peptide · 11 LncRNAs identified · TNF, TLR4, MAPK8 downregulated · PRG4+ cell localization restored","methodology":"Infrapatellar fat pad mesenchymal stem cells were genetically modified to express the CGRP antagonist peptide CGRP8-37. EVs were harvested and characterized for miRNA, protein, and LncRNA content. In vitro testing on dorsal root ganglia and chondrocytes measured inflammatory markers and gene expression. In vivo, EVs were injected intra-articularly in mice with OA; outcomes included pain behavior, cartilage histology, collagen organization, and Substance P levels.","limitations":"Preclinical study in mice — effects may not translate to human OA joints. The genetic modification adds complexity for clinical translation. Substance P reduction was a trend rather than statistically significant. Long-term safety of gene-enhanced EVs and optimal dosing schedules were not established."},{"rthcId":"RPEP-12157","title":"Semaglutide-associated worsening of atypical anorexia nervosa in an adolescent girl: case report.","authors":"Liekens, Lisa; Kaïret, Koen; Elst, Elisabeth F","year":2025,"journal":"BJPsych open, 12(1), e2","doi":"10.1192/bjo.2025.10909","pmid":"41320187","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12158","title":"Once-weekly semaglutide 2·4 mg in an Asian population with obesity, defined as BMI ≥25 kg/m2, in South Korea and Thailand (STEP 11): a randomised, double-blind, placebo-controlled, phase 3 trial.","authors":"Lim, Soo; Buranapin, Supawan; Bao, Xiaolei; Quiroga, María; Park, Kyung Hee; Kang, Jee-Hyun; Rinnov, Anders Rasmussen; Suwanagool, Arisara","year":2025,"journal":"The lancet. Diabetes & endocrinology, 13(10), 838-847","doi":"10.1016/S2213-8587(25)00164-0","pmid":"40825340","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12159","title":"Glucagon-like peptide 1 receptor agonists and cancer risk: advancing precision medicine through mechanistic understanding and clinical evidence.","authors":"Lin, Anqi; Ding, Yanxi; Li, Zhengrui; Jiang, Aimin; Liu, Zaoqu; Wong, Hank Z H; Cheng, Quan; Zhang, Jian; Luo, Peng","year":2025,"journal":"Biomarker research, 13(1), 50","doi":"10.1186/s40364-025-00765-3","pmid":"40140925","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12160","title":"Association of Sodium-Glucose Cotransporter 2 Inhibitors and Glucagon-Like Peptide-1 Receptor Agonists With Risk of Cataract.","authors":"Lin, Bing-Hua; Chuang, Shu-Han; Wu, Lien-Chen; Chen, Yu-Pin; Kuo, Yi-Jie; Chang, Cheng-Hsien","year":2025,"journal":"American journal of ophthalmology, 284, 66-77","doi":"10.1016/j.ajo.2025.12.025","pmid":"41456709","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12161","title":"Semaglutide in the treatment of a patient with type 2 diabetes mellitus, psoriasis, and metabolic dysfunction-associated steatotic liver disease: a case report.","authors":"Lin, Bingting; Huang, Qiuxiang; Weng, Liang; Lin, Lu","year":2025,"journal":"Frontiers in medicine, 12, 1684204","doi":"10.3389/fmed.2025.1684204","pmid":"41020234","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12162","title":"Dual cell-penetrating peptide-conjugated polymeric nanocarriers for miRNA-205-5p delivery in gene therapy of cutaneous squamous cell carcinoma.","authors":"Lin, Cheng-Yu; Fang, Jia-You; Hsiao, Chien-Yu; Lee, Chiang-Wen; Alshetaili, Abdullah; Lin, Zih-Chan","year":2025,"journal":"Acta biomaterialia, 196, 332-349","doi":"10.1016/j.actbio.2025.02.056","pmid":"40015353","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12163","title":"Glucagon-like peptide-1 receptor agonists therapy to attenuate the risk of knee osteoarthritis and total knee replacement in type 2 diabetes mellitus: A nation-wide population-based cohort study.","authors":"Lin, Chih-Ping; Chung, Chi-Hsiang; Lu, Chieh-Hua; Su, Sheng-Chiang; Kuo, Feng-Chih; Liu, Jhih-Syuan; Li, Peng-Fei; Huang, Chia-Luen; Ho, Li-Ju; Chen, Kuan-Chan; Chang, Chun-Yung; Lin, Ming-Shiun; Liu, Yi-Chen; Cheng, An-Che; Lin, Hong-Han; Kuo, Shi-Wen; Lee, Chien-Hsing; Hsieh, Chang-Hsun; Hung, Yi-Jen; Liu, Hsin-Ya; Guo, Lan-Yuen; Chien, Wu-Chien","year":2025,"journal":"Medicine, 104(6), e41243","doi":"10.1097/MD.0000000000041243","pmid":"39928811","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 1,976 propensity-matched T2DM patients (988 GLP-1RA users, 988 non-users) without baseline KOA, GLP-1RA treatment was associated with significantly lower KOA risk: 4.66% vs 8.81% developed KOA (adjusted HR = 0.852, 95% CI 0.784-0.930, P < 0.001).\n\nAmong 744 propensity-matched T2DM patients with existing KOA (372 GLP-1RA users, 372 non-users), GLP-1RA treatment was associated with lower total knee replacement rates: 10.48% vs 18.82% underwent TKR (adjusted HR = 0.913, 95% CI 0.885-0.977, P = 0.015). Kaplan-Meier survival analysis confirmed significantly different cumulative risk curves for both outcomes (log-rank P < 0.001 for both).","whyItMatters":"Knee osteoarthritis is the most common joint disease, affecting over 250 million people worldwide. Total knee replacement — while effective — is a major surgery with significant cost, recovery time, and complication risk. If GLP-1 drugs can reduce both KOA development and the need for TKR, this represents a substantial additional benefit for the hundreds of millions of T2DM patients worldwide. The effect may be mediated through weight loss (reducing mechanical joint stress), anti-inflammatory properties, or emerging evidence that GLP-1 receptors are expressed in cartilage and may directly protect joint tissue.","specificNumbers":"","methodology":"Population-based retrospective cohort study using Taiwan's National Health Insurance Database. 35,762 patients with T2DM were identified. GLP-1RA users were propensity score-matched 1:1 with non-users by sex, age, and inclusion date. Two analyses were performed: KOA development in T2DM without baseline KOA, and TKR rates in T2DM with baseline KOA. Cox proportional hazards regression estimated adjusted hazard ratios over a maximum 5-year follow-up.","limitations":"As a retrospective observational study, it cannot establish causation — GLP-1RA users may differ from non-users in unmeasured ways despite propensity score matching. The study could not determine whether the benefit was driven by weight loss (the most likely explanation), anti-inflammatory effects, or direct joint-protective mechanisms. Specific GLP-1RA agents and doses were not differentiated. The Taiwanese population may have different obesity and OA patterns than other populations. The ICD-based diagnosis of KOA may lack precision compared to imaging or clinical assessment."},{"rthcId":"RPEP-12164","title":"Anti-GPC3 antibody and cell-penetrating peptide CPP44 dual-ligand modified liposomes for targeted delivery of arsenic trioxide in the treatment of hepatocellular carcinoma.","authors":"Lin, Congcong; Sun, Jiamin; Yang, Yun; Pan, Xinyao; Sun, Yifan; Sun, Bin; Gan, Chunli","year":2025,"journal":"Journal of drug targeting, 33(6), 1004-1013","doi":"10.1080/1061186X.2025.2461104","pmid":"39883090","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12165","title":"Microneedle patch with pure drug tips for delivery of liraglutide: pharmacokinetics in rats and minipigs.","authors":"Lin, Hongbing; Liu, Jinbin; Hou, Yulin; Yu, Zhiyan; Hong, Juan; Yu, Jianghong; Chen, Yu; Hu, Jingwen; Xia, Dengning","year":2025,"journal":"Drug delivery and translational research, 15(1), 216-230","doi":"10.1007/s13346-024-01582-1","pmid":"38619705","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The microneedle patch loaded up to 2.21 mg of liraglutide in just 0.9 cm² — nearly two orders of magnitude more drug than conventional dissolving microneedle patches of the same size. Each application delivered up to 0.93 mg into skin with less than 6.8% dosing variability.\n\nCompared to subcutaneous injection, the microneedle patch achieved relative bioavailability of 69.8% in rats and 46.3% in minipigs, with faster initial absorption. In diabetic rats, the patch produced similar blood sugar-lowering effects to injection. After 7 days of daily application to the same site on minipigs, only mild erythema (redness) was observed within the first 4 hours, with no lasting skin irritation.","whyItMatters":"Millions of people use injectable GLP-1 drugs like liraglutide daily, and needle phobia is a real barrier to adherence. A painless patch that delivers the same drug through the skin could dramatically improve patient compliance. This study's innovation — packing pure drug into the needle tips instead of diluting it with fillers — solves the longstanding problem of microneedles not carrying enough medication to be therapeutically useful.","specificNumbers":"","methodology":"Researchers fabricated dissolving microneedle patches with pure liraglutide at the needle tips using a micro-molding technique. They confirmed drug localization using Raman imaging and tested mechanical strength for skin penetration. Pharmacokinetic studies were conducted in Sprague-Dawley rats and Göttingen minipigs, comparing microneedle delivery to subcutaneous injection. Anti-hyperglycemic effects were tested in streptozotocin-induced diabetic rats. Skin tolerability was assessed with 7 days of daily minipig application.","limitations":"This is a preclinical study — no human data yet. The 46.3% bioavailability in minipigs (closer to human skin than rats) means nearly half the drug doesn't reach the bloodstream, which may require larger patches or more frequent application. The study was short-term; long-term skin effects of repeated application are unknown. Manufacturing scalability of pure-drug microneedle tips has not been demonstrated."},{"rthcId":"RPEP-12166","title":"Neurodegeneration and Stroke After Semaglutide and Tirzepatide in Patients With Diabetes and Obesity.","authors":"Lin, Huan-Tang; Tsai, Yung-Fong; Liao, Pei-Lun; Wei, James Cheng-Chung","year":2025,"journal":"JAMA network open, 8(7), e2521016","doi":"10.1001/jamanetworkopen.2025.21016","pmid":"40663350","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12167","title":"The correlation between novel antidiabetic agents utilization and hepatocellular carcinoma incidence in type 2 diabetes patients: a network meta-analysis.","authors":"Lin, Junjie; Ren, Tianshu; Zhao, Qingchun; Tong, Qiang; Liu, Jiahui; Kang, Ye; Yuan, Yuan","year":2025,"journal":"European journal of clinical pharmacology, 81(11), 1643-1658","doi":"10.1007/s00228-025-03899-3","pmid":"40788386","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12168","title":"Semaglutide protects against diabetes-associated cardiac inflammation via Sirt3-dependent RKIP pathway.","authors":"Lin, Kaibin; Wang, Ai; Zhai, Changlin; Zhao, Yun; Hu, Huilin; Huang, Dong; Zhai, Qiwei; Yan, Yan; Ge, Junbo","year":2025,"journal":"British journal of pharmacology, 182(7), 1561-1581","doi":"10.1111/bph.17327","pmid":"39710830","tags":["glp-1-agonists"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"Semaglutide protected diabetic mouse hearts from inflammation-driven damage through a specific molecular pathway: Sirt3 → RKIP → TBK1-NF-κB. In diabetic mice, semaglutide reduced cardiac fibrosis, improved heart function, decreased oxidative stress, and suppressed cardiomyocyte death. The anti-inflammatory effect worked through cAMP/PKA signaling rather than blood sugar reduction — meaning the heart benefits were independent of glucose control.\n\nCritically, when RKIP (Raf kinase inhibitor protein) was knocked out, semaglutide lost its cardioprotective effects, confirming this pathway is essential. The same decrease in RKIP expression and activation of inflammatory signaling was found in human diabetic heart tissue, suggesting this mechanism is clinically relevant.","whyItMatters":"Clinical trials have shown semaglutide reduces cardiovascular events in diabetic patients, but why has been unclear. This study identifies a specific molecular pathway — independent of blood sugar lowering — that explains how semaglutide directly protects the heart from inflammation. This is important because it suggests semaglutide's cardiac benefits aren't just a side effect of better diabetes control but a direct anti-inflammatory action on heart tissue.","specificNumbers":"Sirt3-RKIP-TBK1-NF-κB pathway identified · cAMP/PKA signaling (not glucose lowering) drives effect · RKIP deficiency abolished protection · Human diabetic heart tissue validated pathway · HFD/STZ diabetic mouse model","methodology":"Researchers induced diabetes in mice using high-fat diet plus streptozotocin and treated them with semaglutide. Heart function, fibrosis, oxidative stress, inflammation, and cell death were assessed. RKIP-knockout mice were used to confirm the pathway's necessity. Cell experiments investigated the molecular signaling. Human diabetic heart tissue was examined to validate that the same pathway is disrupted in humans. The Sirt3 activator honokiol was used to further confirm the mechanism.","limitations":"This is primarily an animal study, though it includes validation in human tissue samples. The mouse model of diabetes may not perfectly replicate human diabetic cardiomyopathy. Semaglutide doses used in mice may not directly correspond to human doses. Long-term cardiac outcomes and the durability of the protective effect were not assessed."},{"rthcId":"RPEP-12169","title":"Sacubitril-Valsartan Lowers Blood Pressure in Patients on Dialysis: A Randomized Controlled Multicenter Study.","authors":"Lin, Li; Bian, Weijing; Luo, Qun; Wang, Liang; Liu, Na; Yang, Min; Cen, Jun; Cai, Kedan; Hua, Jia; Gu, Hongwei; Qi, Hualin; Wang, Zhihong; Niu, Jianying; Chen, Yu; Gu, Yizheng; Hu, Chun; Li, Suhua; Li, Yan; Chen, Nan; Li, Xiao","year":2025,"journal":"Kidney diseases (Basel, Switzerland), 11(1), 206-217","doi":"10.1159/000545195","pmid":"40255869","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12170","title":"Identification of novel ACE inhibitory peptides from Nannochloropsis oculata through peptidomics, in silico screening and molecular docking.","authors":"Lin, Liqin; Yuan, Wenwen; Xiao, Jinyan; Jia, Jing; Xie, Youping; Cai, Qingyun; Dai, Congjie; Li, Qingbiao; Wang, Baobei","year":2025,"journal":"Food chemistry, 490, 145073","doi":"10.1016/j.foodchem.2025.145073","pmid":"40505302","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12171","title":"Divergent Risks of Hematologic Malignancies Associated with GLP-1 Receptor Agonists and SGLT2 Inhibitors: Preliminary Findings from a Pilot Network Meta-Analysis.","authors":"Lin, Pao-Yen; Zeng, Bing-Yan; Hsu, Chih-Wei; Suen, Mein-Woei; Hung, Chao-Ming; Stubbs, Brendon; Chen, Yen-Wen; Chen, Tien-Yu; Lei, Wei-Te; Chen, Jiann-Jy; Zeng, Bing-Syuan; Su, Kuan-Pin; Liang, Chih-Sung; Tseng, Ping-Tao","year":2025,"journal":"Biomolecules, 15(11)","doi":"10.3390/biom15111622","pmid":"41301540","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12172","title":"Astragali Radix-Notoginseng Radix et Rhizoma medicine pair prevents cardiac remodeling by improving mitochondrial dynamic balance.","authors":"Lin, Pingping; Chen, Hong; Cui, Zekun; Yu, Boyang; Kou, Junping; Li, Fang","year":2025,"journal":"Chinese journal of natural medicines, 23(1), 54-63","doi":"10.1016/S1875-5364(25)60806-5","pmid":"39855831","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12173","title":"Neuropeptides as regulators of bone metabolism: from molecular mechanisms to traditional Chinese medicine intervention strategies.","authors":"Lin, Qing; Zhao, Biyi; Huang, Jiajia; Chen, Rumeng; Sun, Weipeng; Ye, Qianyun; Yang, Li; Zhu, Xiaofeng; Li, Xiaoyun; Zhang, Ronghua","year":2025,"journal":"Frontiers in pharmacology, 16, 1516038","doi":"10.3389/fphar.2025.1516038","pmid":"40093328","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12174","title":"Integrative multi-omic profiling of the neoantigen landscape of glioblastoma for the development of therapeutic vaccines reveals vast heterogeneity in immunogenic signatures.","authors":"Lin, Qingtang; Wei, Yukui; Xu, Geng; Wang, Leiming; Ling, Feng; Chen, Xiaojie; Cheng, Ye; Zhou, Yiming","year":2025,"journal":"Frontiers in oncology, 15, 1507632","doi":"10.3389/fonc.2025.1507632","pmid":"40190555","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Multi-omic analysis of 24 GBM patients identified an average of 148 mutated genes and 200 mutation sites per patient, with no dominant shared mutations across the cohort. An average of 107 neoantigen candidates were predicted per patient. Very few neoantigens were shared by more than two patients, and no dominant shared neoantigen could be identified.\n\nA minimum of 11 peptides was required to create a bulk vaccine covering all 24 patients, ensuring each patient had at least one targetable neoantigen. The tumor immune microenvironment was dominated by NK cells and Th1 cells. TCR/BCR repertoires showed clustered CDR3 sequences in tumors with reduced diversity compared to peripheral blood, suggesting tumor-specific immune responses were already present but limited.","whyItMatters":"Glioblastoma has a dismal prognosis with median survival around 15 months. Immunotherapy with checkpoint inhibitors has largely failed in GBM. Personalized neoantigen vaccines represent one of the most promising remaining strategies, but this study reveals the fundamental challenge: extreme heterogeneity means each patient needs a bespoke vaccine. Understanding this landscape is essential for designing realistic vaccine strategies that can actually cover patient cohorts.","specificNumbers":"","methodology":"Integrative multi-omic profiling of 24 GBM patients, including whole-exome sequencing (mutations), HLA typing, TCR/BCR repertoire sequencing, and immune cell component analysis from both tumor tissue and peripheral blood mononuclear cells (PBMCs). Neoantigen prediction was based on mutation identification and HLA binding affinity algorithms. The study was designed to inform a planned GBM clinical vaccine trial.","limitations":"The cohort of 24 patients is relatively small and may not capture the full neoantigen diversity of GBM. The study profiled neoantigen candidates computationally but did not validate their immunogenicity through functional T-cell assays. The minimum 11-peptide coverage assumes each patient needs only one neoantigen, which may be insufficient for effective anti-tumor immunity. The study did not assess whether the identified neoantigens would actually elicit therapeutic immune responses."},{"rthcId":"RPEP-12175","title":"The effect of therapeutic massage combined with conventional therapy in children with functional dyspepsia: a systematic review and meta-analysis.","authors":"Lin, Shaohong; Ye, Ruming; Wu, Guanhong; Wu, Lixia; Lin, Ying; Li, Dan; Xie, Namei; Zhang, Huiyue","year":2025,"journal":"Frontiers in pharmacology, 16, 1554438","doi":"10.3389/fphar.2025.1554438","pmid":"40331196","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12176","title":"Efficacy and safety of GLP-1 receptor agonists on weight management and metabolic parameters in PCOS women: a meta-analysis of randomized controlled trials.","authors":"Lin, Shike; Deng, Yan; Huang, Jing; Li, Meiyan; Sooranna, Suren Rao; Qin, Minzhen; Tan, Bing","year":2025,"journal":"Scientific reports, 15(1), 16512","doi":"10.1038/s41598-025-99622-4","pmid":"40360648","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1RAs significantly reduced BMI, body weight, waist circumference, waist-to-hip ratio, and abdominal girth (all P < 0.0001). For glucose homeostasis, they significantly reduced fasting insulin, 2-hour OGTT glucose, and HOMA-IR. HDL was slightly reduced. Hormone levels (DHEAS, SHBG, total/free testosterone, FAI) were unchanged. Safety: increased nausea (P = 0.02), vomiting (P = 0.04), and dizziness (P = 0.03).","whyItMatters":"PCOS is the most common endocrine disorder in reproductive-age women, and weight management is central to its treatment. Metformin has been the go-to medication but has limited weight loss effects. GLP-1 drugs offer substantially greater weight and metabolic improvements. For PCOS women struggling with weight — which drives insulin resistance, hormonal imbalance, and infertility — GLP-1 drugs could be transformative.","specificNumbers":"","methodology":"Systematic review and meta-analysis of RCTs from PubMed, EMBASE, Cochrane Library, Web of Science, and Google Scholar through October 2024. Included adult PCOS women treated with GLP-1RAs versus metformin or placebo. Primary outcomes: anthropometric measures. Secondary outcomes: glucose homeostasis, hormones, lipids, and safety.","limitations":"The meta-analysis doesn't specify the number of included RCTs or total participants. Most PCOS GLP-1RA trials are small. The lack of hormone level changes may reflect short study durations — hormonal improvements from weight loss can take months. HDL reduction is a concern and needs monitoring. No data on fertility outcomes, menstrual regularity, or long-term PCOS disease course was included. Specific GLP-1RA agents and doses varied across studies."},{"rthcId":"RPEP-12177","title":"Elevated LL-37/FPR2 Axis and its Regulatory Role for Gingival Fibroblasts in Periodontitis.","authors":"Lin, Tingting; Cui, Zhurong; Shen, Yue; Yang, Ruhan; Yu, Weijun; Hu, Shucheng; Shi, Yuanjie; Jiang, Bin; Jin, Min; Lu, Eryi; Gu, Yuting","year":2025,"journal":"International dental journal, 75(6), 103943","doi":"10.1016/j.identj.2025.103943","pmid":"41072077","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12178","title":"Exploring the potential role of C-peptide in type 2 diabetes management.","authors":"Lin, YeunYi; McCrimmon, Rory J; Pearson, Ewan R","year":2025,"journal":"Diabetic medicine : a journal of the British Diabetic Association, 42(3), e15469","doi":"10.1111/dme.15469","pmid":"39797595","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"This review found that C-peptide — a byproduct released when the pancreas makes insulin — is underused in managing type 2 diabetes. While it's well established as a diagnostic tool for type 1 diabetes, the evidence suggests C-peptide levels can also predict how well patients respond to different diabetes medications and help forecast disease progression in type 2 diabetes. The review highlights a gap between C-peptide's potential clinical value in T2D and how little it's actually used in practice.","whyItMatters":"Type 2 diabetes treatment is often trial-and-error — patients try medications and switch if they don't work. If C-peptide testing could predict which drugs will work best for a given patient, it would save time, money, and the health consequences of poorly controlled blood sugar. This review makes the case that a simple, already-available blood test is being overlooked as a tool for personalizing diabetes care.","specificNumbers":"","methodology":"The authors conducted a narrative review of published literature examining C-peptide levels in type 2 diabetes. They synthesized evidence on how C-peptide changes over the course of T2D, its relationship to drug response, its role in treatment strategy decisions, and its ability to predict future outcomes.","limitations":"As a narrative review, this paper identifies gaps and synthesizes trends rather than providing quantitative meta-analytic evidence. The authors acknowledge that C-peptide's utility in T2D has not been extensively studied, meaning much of their argument rests on limited data and the need for future research rather than strong existing evidence."},{"rthcId":"RPEP-12179","title":"Comparative cardiovascular effectiveness of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors in atherosclerotic cardiovascular disease phenotypes: a systematic review and meta-analysis.","authors":"Lin, Yu-Min; Wu, Jheng-Yan; Lee, Mei-Chuan; Su, Chen-Lun; Toh, Han Siong; Chang, Wei-Ting; Chen, Sih-Yao; Kuo, Fang-Hsiu; Tang, Hsin-Ju; Liao, Chia-Te","year":2025,"journal":"European heart journal. Cardiovascular pharmacotherapy, 11(2), 174-189","doi":"10.1093/ehjcvp/pvae093","pmid":"39923808","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12180","title":"Effectiveness of tirzepatide in patients with HFpEF using a target trial emulation retrospective cohort study.","authors":"Lin, Yu-Min; Liao, Kuang-Ming; Yu, Tsung; Wu, Jheng-Yan; Lai, Chih-Cheng","year":2025,"journal":"Nature communications, 16(1), 4471","doi":"10.1038/s41467-025-59616-2","pmid":"40368924","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12181","title":"MOTS-c-modified functional self-assembly peptide hydrogels enhance the activity of nucleus pulposus-derived mesenchymal stem cells of intervertebral disc degeneration.","authors":"Lin, Yuan; Yang, Ruo-Yu; Li, Jie; Shao, Shan-Zhong; Shi, Xiang-Qin; Huang, Zhi-Wei; Zhang, Shu-Hai; Liu, Fu-Jun; Zhang, Yin-Shun; Zhang, Sheng-Quan; Zhang, Su-Mei; Wen, Tian-Yong; Tao, Hui","year":2025,"journal":"Materials today. Bio, 32, 101872","doi":"10.1016/j.mtbio.2025.101872","pmid":"40510834","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12182","title":"Comparative effectiveness of therapies for sleep-disordered breathing in heart failure patients: A comprehensive systematic review and network meta-analysis.","authors":"Lin, Yuhan; Chen, Ying; Tu, Wenqing; Mai, Bifang; Guo, Danying; Li, Yuan; Chen, Yongtong; Xie, Shuanglun; Chen, Yuyang","year":2025,"journal":"Respiratory medicine, 236, 107907","doi":"10.1016/j.rmed.2024.107907","pmid":"39645004","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12183","title":"Glucagon-Like Peptide-1 Receptor Agonists in the Prevention of Ischemic Stroke: Therapeutic Potential and Mechanisms.","authors":"Lin, Zhenzong; Li, Zixiao; Jia, Qian","year":2025,"journal":"Journal of stroke, 27(3), 289-301","doi":"10.5853/jos.2025.00584","pmid":"41084286","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12184","title":"Calcitonin Gene-Related Peptide Ameliorates Experimental Dry Eye Disease.","authors":"Lin, Zhirong; Verma, Bhupender; Zhu, Shuyan; Zidan, Asmaa A; Najafi, Sheyda; Naderi, Amirreza; Elbasiony, Elsayed; Yin, Jia","year":2025,"journal":"Investigative ophthalmology & visual science, 66(11), 58","doi":"10.1167/iovs.66.11.58","pmid":"40853308","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CGRP expression was significantly reduced in both the cornea and trigeminal ganglion of mice with experimentally induced dry eye disease, establishing a biological rationale for replacement therapy.\n\nIn cultured human corneal epithelial cells under stress conditions, CGRP promoted cell proliferation, reduced programmed cell death, and lowered expression of inflammatory cytokines TNF-α, IL-1β, and IL-6.\n\nIn live mice with dry eye, topical CGRP applied three times daily for two weeks significantly decreased corneal fluorescein staining scores (a measure of surface damage), increased tear break-up time, and preserved the corneal epithelium. CGRP also reduced infiltrating CD45+ immune cells and inflammatory cytokine expression in the cornea, though it did not significantly affect immune cells in the conjunctiva.","whyItMatters":"Dry eye disease affects hundreds of millions of people worldwide and current treatments often provide only symptom relief rather than addressing underlying causes. The discovery that CGRP is specifically depleted in dry eye and that replacing it with simple eye drops can both reduce inflammation and promote corneal healing addresses a root cause of the disease rather than just masking symptoms.","specificNumbers":"","methodology":"The study combined in vitro and in vivo approaches. Human corneal epithelial cells were cultured under hyperosmotic stress to simulate dry eye conditions, then treated with CGRP to assess effects on viability, proliferation, migration, and cell death. For the animal model, desiccating stress was used to induce dry eye in mice. CGRP or albumin control eye drops were applied three times daily for two weeks. Clinical dry eye parameters were measured, and corneal and conjunctival tissues were analyzed using immunostaining and flow cytometry for cell proliferation and inflammatory markers.","limitations":"This is a mouse study and results may not directly translate to humans. The dry eye model uses desiccating stress, which mimics only one type of dry eye disease. The two-week treatment period is relatively short, so long-term efficacy and safety are unknown. Sample sizes per group are not specified in the abstract. CGRP did not affect conjunctival inflammation, suggesting its benefits may be limited to the cornea."},{"rthcId":"RPEP-12185","title":"Naturopathic Management to Taper Off Glucagon-Like Peptide-1 Receptor Agonist Therapy in Type 2 Diabetes: A Case Report.","authors":"Linder, Leah","year":2025,"journal":"Integrative medicine (Encinitas, Calif.), 24(1), 26-30","doi":null,"pmid":"39896831","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12186","title":"Injections vs. Scalpels: Where Do Surgery and GLP-1's Align in Modern Obesity treatment?","authors":"Lindquist, Matthew; Varghese, Esther; Bassham, Cooper","year":2025,"journal":"Missouri medicine, 122(4), 340-344","doi":null,"pmid":"40787019","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12187","title":"Improvements in Cardiometabolic Risk Factors by Weight Reduction: A Post Hoc Analysis of Adults With Obesity Randomly Assigned to Tirzepatide.","authors":"Linetzky, Bruno; Sattar, Naveed; Verma, Subodh; Krumholz, Harlan M; Xie, Cathy Chang; Hoffmann, Hunter T; Zimner-Rapuch, Sarah; Torcello-Gómez, Amelia; Stefanski, Adam","year":2025,"journal":"Annals of internal medicine, 178(8), 1095-1105","doi":"10.7326/ANNALS-24-02623","pmid":"40550133","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12188","title":"Combined liraglutide and metformin therapy in overweight or obese women with polycystic ovary syndrome: A systematic review and meta-analysis.","authors":"Ling, Jing; Wang, Tiantian; Huang, Wenrui; Zhen, Yuhua; Zhang, Mingzi; Fang, Xingzi; Song, Wencong; Du, Xuelian","year":2025,"journal":"Diabetes, obesity & metabolism, 27(11), 6139-6153","doi":"10.1111/dom.70028","pmid":"40855964","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12189","title":"Targeting oncofetal fibronectin and neuropilin-1 in solid tumors with PL2 peptide.","authors":"Lingasamy, Prakash; Tobi, Allan; Kurm, Kaarel; Tammik, Olav; Teesalu, Tambet","year":2025,"journal":"Scientific reports, 15(1), 29369","doi":"10.1038/s41598-025-11299-x","pmid":"40789864","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12190","title":"Circulating Antimicrobial Peptides as Biomarkers of Inflammation and Airway Dysfunction After Marathon Running.","authors":"Lingitz, Marie-Therese; Kühtreiber, Hannes; Auer, Lisa; Mildner, Michael; Krenn, Claus G; Aigner, Clemens; Moser, Bernhard; Bekos, Christine; Ankersmit, Hendrik Jan","year":2025,"journal":"Biology, 14(7)","doi":"10.3390/biology14070825","pmid":"40723384","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Serum levels of hBD-2 and S100A8/A9 were significantly elevated immediately after the race in both marathon and half-marathon runners compared to baseline and sedentary controls, then returned to baseline by seven days postrace.\n\nIn runners who developed exercise-induced bronchoconstriction (EIB), S100A8 levels remained slightly elevated during recovery, and hBD-2 was modestly increased. Critically, S100A8 levels showed a negative correlation with lung function parameters including forced expiratory volume and mid-expiratory flows — meaning higher peptide levels were associated with worse airway function. Angiogenin and major basic protein (MBP) did not show the same pattern.","whyItMatters":"Exercise-induced bronchoconstriction affects up to 50% of elite endurance athletes and can impair performance and health. Currently, there are no simple blood-based biomarkers to predict which athletes are at risk. If antimicrobial peptides like S100A8 can identify susceptible individuals before symptoms develop, it could enable personalized prevention strategies — such as modified training regimens, pre-treatment protocols, or environmental controls — to protect athletes' airway health during intense endurance competition.","specificNumbers":"","methodology":"A prospective study enrolled 34 marathon runners and 36 half-marathon runners, with 30 sedentary controls. Blood samples were collected at three time points: baseline (before the race), immediately postrace, and seven days postrace. Serum concentrations of five antimicrobial peptides (angiogenin, hBD-2, MBP, S100A8, and S100A8/A9) were measured using ELISA. Lung function was assessed by spirometry at each time point to identify exercise-induced bronchoconstriction.","limitations":"The study had a moderate sample size (70 runners, 30 controls) and was conducted in the context of a single race event, limiting generalizability to other endurance activities. The correlation between S100A8 and lung function, while statistically significant, was modest in magnitude. The study measured circulating peptide levels but did not assess local airway concentrations, which may differ. It cannot establish whether elevated peptides cause airway dysfunction or are simply markers of it. Individual variability in training status, race conditions, and pre-existing respiratory conditions may confound results."},{"rthcId":"RPEP-12191","title":"Once-weekly IcoSema versus once-weekly semaglutide in adults with type 2 diabetes: the COMBINE 2 randomised clinical trial.","authors":"Lingvay, Ildiko; Benamar, Malik; Chen, Liming; Fu, Ariel; Jódar, Esteban; Nishida, Tomoyuki; Riveline, Jean-Pierre; Yabe, Daisuke; Zueger, Thomas; Réa, Rosângela","year":2025,"journal":"Diabetologia, 68(4), 739-751","doi":"10.1007/s00125-024-06348-5","pmid":"39820580","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Once-weekly IcoSema (combining insulin icodec and semaglutide in a single injection) demonstrated superior HbA1c reduction compared to semaglutide alone over 52 weeks: -1.35% vs -0.90% (treatment difference -0.44%, p<0.0001). IcoSema also produced significantly greater fasting glucose reduction (-2.48 vs -1.43 mmol/L). However, semaglutide alone was significantly better for weight: -3.70 kg vs +0.84 kg with IcoSema. Rates of clinically significant hypoglycemia and gastrointestinal side effects were similar between groups.","whyItMatters":"Many type 2 diabetes patients on GLP-1 receptor agonists still don't achieve adequate blood sugar control and need insulin added. IcoSema combines both peptide drugs into a single weekly injection, simplifying treatment while delivering superior glucose control. The trade-off — less weight loss than semaglutide alone — reflects the insulin component but the convenience of one injection could improve patient adherence.","specificNumbers":"n=683 · 52 weeks · HbA1c: -1.35% vs -0.90% (p<0.0001) · fasting glucose: -2.48 vs -1.43 mmol/L · weight: +0.84 kg vs -3.70 kg · 121 sites · 13 countries · similar hypoglycemia rates","methodology":"Phase IIIa, 52-week, randomized, open-label, parallel-group trial across 121 sites in 13 countries. 683 adults with type 2 diabetes (HbA1c 7.0-10.0%) inadequately managed on GLP-1 RA therapy were randomized 1:1 to once-weekly IcoSema or semaglutide 1.0 mg. Primary endpoint: change in HbA1c at week 52 with superiority testing. Secondary endpoints: fasting glucose, body weight, and hypoglycemia rates.","limitations":"Open-label design means participants and investigators knew which treatment they received, potentially introducing bias. Funded by Novo Nordisk (manufacturer). The weight gain with IcoSema vs weight loss with semaglutide alone may limit its appeal. Semaglutide 1.0 mg comparator is not the highest available dose (2.4 mg for weight management)."},{"rthcId":"RPEP-12192","title":"Once-weekly semaglutide 7·2 mg in adults with obesity and type 2 diabetes (STEP UP T2D): a randomised, controlled, phase 3b trial.","authors":"Lingvay, Ildiko; Bergenheim, Sara J; Buse, John B; Freitas, Paula; Garvey, W Timothy; Harder-Lauridsen, Nina M; Rosenstock, Julio; Sahu, Kushal; Wharton, Sean","year":2025,"journal":"The lancet. Diabetes & endocrinology, 13(11), 935-948","doi":"10.1016/S2213-8587(25)00225-6","pmid":"40961953","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12193","title":"Patient preferences for the preventive treatment of episodic migraine in the United States: A discrete-choice experiment.","authors":"Lipton, Richard B; Gandhi, Pranav; Myers, Kelley; Bussberg, Cooper; Stokes, Jonathan; Nahas, Stephanie J","year":2025,"journal":"Headache, 65(9), 1541-1553","doi":"10.1111/head.14974","pmid":"40552555","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In a discrete-choice experiment, 70-85% of episodic migraine patients preferred an oral daily pill profile (like the CGRP receptor antagonist atogepant) over injectable CGRP monoclonal antibody profiles, even when efficacy was similar. The two most important treatment attributes were: (1) absence of nausea and (2) oral pill administration rather than injection or infusion. Patients valued oral delivery approximately 2.5 times more than avoiding mild nausea.","whyItMatters":"CGRP-targeting therapies have transformed migraine prevention, but patients now have both oral peptide receptor antagonists (gepants) and injectable monoclonal antibodies to choose from. Understanding patient preferences helps clinicians align treatment choices with patient values, potentially improving adherence and outcomes.","specificNumbers":"70.9-85.4% preferred oral atogepant-like profile vs injectable mAbs · 70.7-73.8% vs composite mAb class · oral > injection valued ~2.5x more than avoiding mild nausea · 7 attributes tested","methodology":"Discrete-choice experiment survey administered to US adults (aged 18-80) with episodic migraine who were CGRP therapy-naïve, between November-December 2020. Respondents compared pairs of hypothetical treatment profiles defined by 7 attributes with varying levels. Preference weights estimated conditional relative importance and predicted probability of preferring different treatment profiles.","limitations":"Survey-based stated preferences may not perfectly predict real-world treatment choices. Respondents were CGRP therapy-naïve, so preferences reflect expectations rather than experience. The study was conducted in 2020 when some CGRP therapies were relatively new. Funded by AbbVie (atogepant manufacturer), which may introduce bias in study design and framing."},{"rthcId":"RPEP-12194","title":"Incretin-Based Adjunct to Background Insulin Treatment for Managing Body Weight Excess in Type 1 Diabetes: An Expert Opinion Viewpoint From the Italian Association of Clinical Endocrinologists.","authors":"Lisco, Giuseppe; De Tullio, Anna; Disoteo, Olga Eugenia; Armigliato, Michela; Guastamacchia, Edoardo; Marucci, Simonetta; De Pergola, Giovanni; Papini, Enrico; Chianelli, Marco; Frasoldati, Andrea; De Geronimo, Vincenzo; Triggiani, Vincenzo","year":2025,"journal":"Diabetes/metabolism research and reviews, 41(6), e70073","doi":"10.1002/dmrr.70073","pmid":"40914967","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12195","title":"Utility of Gallium-68-DOTATATE PET CT in Surveillance of Resected Gastroenteropancreatic NET.","authors":"Lithgow, Kirstie; Samnani, Sunil; Yeo, Caitlin T; Chan, Denise","year":2025,"journal":"Journal of clinical medicine, 14(23)","doi":"10.3390/jcm14238545","pmid":"41375845","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12196","title":"Interaction Between Glucagon-like Peptide 1 and Its Analogs with Amyloid-β Peptide Affects Its Fibrillation and Cytotoxicity.","authors":"Litus, Ekaterina A; Shevelyova, Marina P; Vologzhannikova, Alisa A; Deryusheva, Evgenia I; Chaplygina, Alina V; Rastrygina, Victoria A; Machulin, Andrey V; Alikova, Valeria D; Nazipova, Aliya A; Permyakova, Maria E; Dotsenko, Victor V; Permyakov, Sergei E; Nemashkalova, Ekaterina L","year":2025,"journal":"International journal of molecular sciences, 26(9)","doi":"10.3390/ijms26094095","pmid":"40362335","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12197","title":"Scratching promotes allergic inflammation and host defense via neurogenic mast cell activation.","authors":"Liu, Andrew W; Zhang, Youran R; Chen, Chien-Sin; Edwards, Tara N; Ozyaman, Sumeyye; Ramcke, Torben; McKendrick, Lindsay M; Weiss, Eric S; Gillis, Jacob E; Laughlin, Colin R; Randhawa, Simran K; Phelps, Catherine M; Kurihara, Kazuo; Kang, Hannah M; Nguyen, Sydney-Lam N; Kim, Jiwon; Sheahan, Tayler D; Ross, Sarah E; Meisel, Marlies; Sumpter, Tina L; Kaplan, Daniel H","year":2025,"journal":"Science (New York, N.Y.), 387(6733), eadn9390","doi":"10.1126/science.adn9390","pmid":"39883751","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12198","title":"Some Risks of Gastrointestinal Adverse Events Associated With Glucagon-Like PEPTIDE-1 Receptor Agonists Are Likely Explained by BMI.","authors":"Liu, Benjamin Douglas; Veccia, Donovan; Sun, Yan; Song, Gengqing","year":2025,"journal":"Alimentary pharmacology & therapeutics, 62(1), 77-80","doi":"10.1111/apt.70190","pmid":"40356540","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12199","title":"Knowledge, attitude and practice toward liraglutide and semaglutide among endocrinology medical staff.","authors":"Liu, Bingling; Wu, Xueyi; Zou, Xiao; Sheng, Jianjian; Yu, Jie","year":2025,"journal":"Scientific reports, 15(1), 11533","doi":"10.1038/s41598-025-96545-y","pmid":"40185826","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 265 endocrinology medical staff surveyed, the average knowledge score was 11.77 out of 16 (73.6%), the attitude score was 39.30 out of 50 (78.6%), and the practice score was 27.70 out of 35 (79.1%). While these scores are above midpoint, they indicate meaningful gaps in professional proficiency with these commonly prescribed medications.\n\nStructural equation modeling revealed strong causal pathways: knowledge significantly influenced both attitude (β = 0.976, P < 0.001) and practice (β = 1.289, P < 0.001), while attitude also significantly affected practice (β = 0.627, P < 0.001). This confirms that improving knowledge is the most effective lever for improving prescribing behavior.","whyItMatters":"GLP-1 receptor agonists are among the fastest-growing drug classes in medicine, yet this study shows that even endocrinology specialists — the doctors most likely to prescribe them — have significant knowledge gaps. As these medications expand into obesity treatment and cardiovascular protection, ensuring healthcare providers have thorough, up-to-date knowledge is critical for patient safety and optimal outcomes.","specificNumbers":"","methodology":"This was a cross-sectional study conducted from September to December 2023 at the First People's Hospital of Jiujiang, China. Endocrinology medical staff completed a self-administered questionnaire assessing their knowledge (scored 0–16), attitudes (scored 10–50), and practices (scored 7–35) regarding liraglutide and semaglutide. Structural equation modeling was used to analyze the relationships between knowledge, attitude, and practice.","limitations":"This was a single-center study at one hospital in China, limiting generalizability to other healthcare systems and countries. Self-reported questionnaires may be subject to social desirability bias, and actual knowledge and practice could differ from what respondents report. The study did not compare knowledge levels between different specialties or between doctors and nurses. Cultural and healthcare system differences mean findings may not apply directly to Western medical settings."},{"rthcId":"RPEP-12200","title":"Disproportionality analysis of GLP-1 receptor agonists combined with metformin based on the FAERS database.","authors":"Liu, Boyi; Huang, Ruizhe; Zhang, Wenchao; Tian, Jie; Yao, Xian; Chen, Danna","year":2025,"journal":"Scientific reports, 15(1), 34673","doi":"10.1038/s41598-025-02394-0","pmid":"41053152","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Analysis of 48,214 FAERS reports (57.5% female) found that GLP-1 receptor agonist plus metformin combination therapy had lower adverse event rates than either drug alone (monotherapy). Common AEs were nausea and weight loss. Unexpected safety signals included kidney injury and pancreatic cancer. Gender-specific patterns emerged: males reported more renal calculi and early-onset AEs (within 30 days), while females experienced more delayed AEs (beyond 360 days). Weight loss was consistent across all demographic groups.","whyItMatters":"GLP-1 RAs combined with metformin is one of the most common diabetes drug combinations prescribed worldwide. This large pharmacovigilance analysis of 20 years of adverse event data provides clinicians with actionable safety insights, including the surprising finding that combination therapy appears safer than monotherapy and the identification of gender-specific risk patterns that could inform personalized monitoring strategies.","specificNumbers":"","methodology":"Retrospective disproportionality analysis of the FDA Adverse Event Reporting System (FAERS) database from 2004 to 2024. The reporting odds ratio (ROR) was used as the primary measure, with Bayesian confidence propagation neural network (BCPNN) for sensitivity analysis. Adverse events were compared between GLP-1 RA/metformin combination therapy and monotherapy with either drug alone. Stratified analyses were performed by gender, age, and body weight.","limitations":"FAERS is a voluntary adverse event reporting system subject to reporting bias, underreporting, and confounding by indication. The finding that combination therapy had lower AE rates than monotherapy may reflect healthier-user bias or differences in prescribing patterns rather than true superior safety. Disproportionality analysis can identify safety signals but cannot establish causation. The unexpected signals for kidney injury and pancreatic cancer require prospective confirmation."},{"rthcId":"RPEP-12201","title":"Characterization and neurotherapeutic evaluation of venom polypeptides identified from Vespa magnifica: The role of Mastoparan-M in Parkinson's disease intervention.","authors":"Liu, Chaojie; Li, Xiaoyu; Chen, Mingran; Liu, Yunyun; Li, Kunkun; Wang, Dexiao; Yang, Zhibin; Guo, Yunjiao; Zhao, Yu; Zhao, Hairong; Zhang, Chenggui","year":2025,"journal":"Journal of ethnopharmacology, 343, 119481","doi":"10.1016/j.jep.2025.119481","pmid":"39947367","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12202","title":"Sodium-Glucose Cotransporter 2 Inhibitors Prevent Nephrolithiasis in Patients with Diabetes: A TriNetX-Based Real-World Global Comparison.","authors":"Liu, Chia-Min; Hsiang-Te Tsai, Daniel; Tung, Hsiu-Ting; Lu, Ze-Hong; Chia-Cheng Lai, Edward; Liu, Chan-Jung","year":2025,"journal":"Kidney360","doi":"10.34067/KID.0000000981","pmid":"41117521","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12203","title":"Reduction of Hepatic Fat Content by Dulaglutide for the Treatment of Diabetes Mellitus: A Two-Centre Open, Single-Arm Trial.","authors":"Liu, Chuanfeng; Xin, Yu; Huang, Yajing; Xu, Lili; Zhou, Ruizhi; Wang, Yangang; Wang, Wei","year":2025,"journal":"Endocrinology, diabetes & metabolism, 8(1), e70021","doi":"10.1002/edm2.70021","pmid":"39718468","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12204","title":"GIPR-Ab/GLP-1 peptide-antibody conjugate requires brain GIPR and GLP-1R for additive weight loss in obese mice.","authors":"Liu, Clarissa M; Killion, Elizabeth A; Hammoud, Rola; Lu, Shu-Chen; Komorowski, Renee; Liu, Tongyu; Kanke, Matt; Thomas, Veena A; Cook, Kevin; Sivits, Glenn N; Ben, Aerielle B; Atangan, Larissa I; Hussien, Rajaa; Tang, Amy; Shkumatov, Artem; Li, Chi-Ming; Drucker, Daniel J; Véniant, Murielle M","year":2025,"journal":"Nature metabolism, 7(6), 1266-1281","doi":"10.1038/s42255-025-01295-w","pmid":"40301582","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12205","title":"A halophilic metalloprotease from Salinivibrio sp. YH4 and its application in antioxidant peptide production.","authors":"Liu, Dan; Xiao, Yuyang; Wei, Yingying; Xie, Maojia; Huang, Yu; Gan, Chaoyu; He, Hailun","year":2025,"journal":"Frontiers in microbiology, 16, 1595109","doi":"10.3389/fmicb.2025.1595109","pmid":"40458704","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12206","title":"A modular metalloprotein in situ vaccine for cancer immunotherapy in mouse models of breast cancer.","authors":"Liu, Dingkang; Tian, Jing; Yu, Lichao; Luo, Hong; Rong, Haibo; Tong, Yue; Gao, Xiangdong; Yin, Jun","year":2025,"journal":"Science translational medicine, 17(825), eadr1777","doi":"10.1126/scitranslmed.adr1777","pmid":"41259539","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12207","title":"Navigating compounded semaglutide: what health care providers need to know.","authors":"Liu, Grace; Jarema, Marissa; Mo, Millie; Stievater, Trish","year":2025,"journal":"The American journal of managed care, 31(9), 480-484","doi":"10.37765/ajmc.2025.89787","pmid":"40966636","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies several key concerns with compounded semaglutide:\n\n1. Quality control gaps: Compounded semaglutide products currently available may lack the rigorous quality controls historically associated with compounded medications, leading to risks of dosing errors and adverse outcomes.\n\n2. Fraudulent products: The global compounded semaglutide market has seen batches of counterfeit products, adding a layer of safety risk beyond quality variation.\n\n3. Regulatory complexity: While compounding is legal when following federal and state regulations, the line between lawful and unlawful compounding has become blurred in the semaglutide market.\n\n4. Provider opportunity: Pharmacists and healthcare providers are uniquely positioned to direct patients to legitimate compounded sources, counsel on proper dosage and administration, and minimize safety risks.","whyItMatters":"Millions of patients want semaglutide for diabetes or weight management but face either drug shortages or prohibitive costs. The resulting turn to compounded alternatives has created a public health concern where patients may be receiving products of unknown quality, potency, or even authenticity. This review provides essential guidance for the healthcare professionals who are patients' first line of defense.","specificNumbers":"","methodology":"Narrative review examining the implications of compounded semaglutide products on the healthcare system, including analysis of safety concerns, efficacy questions, and regulatory status. The review synthesizes information about compounding regulations, market dynamics, and reported quality issues.","limitations":"This is a narrative review without systematic search methodology or quality assessment of included sources. It focuses on the U.S. regulatory landscape and may not fully apply to other countries. The review does not provide quantitative data on adverse event rates from compounded semaglutide or head-to-head comparisons with FDA-approved products. The rapidly evolving regulatory environment may render some specifics outdated quickly."},{"rthcId":"RPEP-12208","title":"Dual activation of GCGR/GLP1R signaling ameliorates intestinal fibrosis via metabolic regulation of histone H3K9 lactylation in epithelial cells.","authors":"Liu, Han; Hong, Yujie; Chen, Hui; Wang, Xianggui; Dong, Jiale; Li, Xiaoqian; Shi, Zihan; Zhao, Qian; Zhou, Longyuan; Wang, JiaXin; Zeng, Qiuling; Tang, Qinglin; Liu, Qi; Rieder, Florian; Chen, Baili; Chen, Minhu; Wang, Rui; Zhang, Yao; Mao, Ren; Jiang, Xianxing","year":2025,"journal":"Acta pharmaceutica Sinica. B, 15(1), 278-295","doi":"10.1016/j.apsb.2024.11.017","pmid":"40041889","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12209","title":"Pharmacodynamics, pharmacokinetics, and toxicology of Fc-growth hormone fusion protein in macaques.","authors":"Liu, Han; Peng, Binghuai; Zhou, Baisong; Zhang, Yu; Liu, Yunnan; Liu, Yulin; Sun, Ruixin; Li, Zhuonan; Zhu, Qiumei; Yu, Lu; Fu, Ruili; Wang, Qiong; Liu, Jinghui; Pang, Chunying","year":2025,"journal":"Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society, 81, 101648","doi":"10.1016/j.ghir.2025.101648","pmid":"40120208","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12210","title":"De novo design of self-assembling peptides with antimicrobial activity guided by deep learning.","authors":"Liu, Huayang; Song, Zilin; Zhang, Yu; Wu, Bihan; Chen, Dinghao; Zhou, Ziao; Zhang, Hongyue; Li, Sangshuang; Feng, Xinping; Huang, Jing; Wang, Huaimin","year":2025,"journal":"Nature materials, 24(8), 1295-1306","doi":"10.1038/s41563-025-02164-3","pmid":"40087536","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12211","title":"Skin transcriptome of lenok trout (Brachymystax lenok) provides new insight on lectin genes and immune response mechanisms to Aeromonas salmonicida infection.","authors":"Liu, Hui; Wang, Maolin; Du, Jiayu; Wang, Shuai; Zhang, Zheng; He, Tingting; Wang, Yuang; Chen, Yan; Wang, Wei; Li, Xuejie","year":2025,"journal":"Comparative biochemistry and physiology. Part D, Genomics & proteomics, 54, 101439","doi":"10.1016/j.cbd.2025.101439","pmid":"39933312","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12212","title":"GLP-1RA in JBMMSCs promoted osteogenic differentiation via modulating CREB and BRD4 signaling mediated proliferation and stemness.","authors":"Liu, Huiming; Tian, Yawei; Bao, Xiaoxue; Li, Yukun","year":2025,"journal":"Scientific reports, 15(1), 40773","doi":"10.1038/s41598-025-24633-0","pmid":"41258401","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide significantly ameliorated osteoporosis in rats when combined with jaw bone marrow mesenchymal stem cell (JBMMSC) intervention. The drug markedly increased calcified nodule formation and alkaline phosphatase (ALP) activity, demonstrating enhanced osteogenic potential.\n\nMechanistically, semaglutide operates through dual pathways: (1) promoting osteogenic and adipogenic differentiation via the BMP2/STAT3/TET3/SHP2 signaling axis, and (2) preserving stem cell stemness and proliferation via the CREB/YAP/BRD4 axis. Western blot analysis confirmed significant upregulation of p-CREB, OCT4, BMP2, and RUNX2 proteins in semaglutide-treated JBMMSCs. These mechanisms were validated by rescue experiments, confirming the dual pathway model.","whyItMatters":"GLP-1 receptor agonists like semaglutide are already prescribed to millions for obesity and diabetes. If they also protect and regenerate bone, this could be a significant added benefit — especially since osteoporosis is common in the same aging populations that use these drugs. Jaw osteoporosis specifically affects dental implant success and oral health in elderly patients, making this a practically relevant finding.","specificNumbers":"","methodology":"The study used both bioinformatics analysis (GEO database) and experimental approaches. JBMMSCs were isolated from rat mandibles and characterized by flow cytometry. In vivo, stem cells were injected via tail vein into osteoporotic rat models and assessed with HE staining. In vitro, optimal semaglutide concentrations were determined using CCK-8 viability, colony formation, and scratch migration assays. Osteogenic differentiation was assessed by ALP and Alizarin Red S staining; adipogenic differentiation by Oil Red O staining. Molecular signaling was analyzed by Western blotting and immunofluorescence.","limitations":"This is an animal study in rats, and jaw bone biology in rats differs from humans. The osteoporosis model may not fully replicate human disease. The stem cell tail vein injection approach is not a standard clinical practice. Specific quantitative data on bone density improvement or sample sizes were not provided in the abstract. Long-term effects and optimal dosing for bone applications remain unknown."},{"rthcId":"RPEP-12213","title":"Tongbian decoction inhibits cell autophagy via PI3K/Akt/mTOR signaling pathway to treat constipation rats.","authors":"Liu, Jiali; Ji, Li; Wang, Yue; Chen, Xingrui; Wan, Yemin; Qian, Haihua; Zhang, Dan","year":2025,"journal":"Journal of ethnopharmacology, 339, 119139","doi":"10.1016/j.jep.2024.119139","pmid":"39571695","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12214","title":"Rational design of dual-agonist peptides targeting GLP-1 and NPY2 receptors for regulating glucose homeostasis and body weight with minimal nausea and emesis.","authors":"Liu, Jing; Lu, Weiwen; Wu, Han; Yan, Zhiming; Liu, Yun; Tang, Chunli; Chen, Yangxin; Wang, Shuang; Tang, Weizhong; Han, Jing; Wei, Changhong; Jiang, Neng","year":2025,"journal":"European journal of medicinal chemistry, 287, 117320","doi":"10.1016/j.ejmech.2025.117320","pmid":"39892093","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12215","title":"Recent progress in nanoparticle-mediated RNA interference in insects: Unveiling new frontiers in pest control.","authors":"Liu, Jisheng; He, Qiuying; Lin, Xianfeng; Smagghe, Guy","year":2025,"journal":"Journal of insect physiology, 167, 104884","doi":"10.1016/j.jinsphys.2025.104884","pmid":"40939831","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12216","title":"Exendin-4, a GLP-1 receptor agonist, suppresses diabetic retinopathy in vivo and in vitro.","authors":"Liu, Jufen; Wang, Huijing; Huang, Cuiting","year":2025,"journal":"Archives of physiology and biochemistry, 131(1), 1-10","doi":"10.1080/13813455.2023.2274279","pmid":"37920998","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Exendin-4 inhibited the progression of diabetic retinopathy in both a high-glucose-induced human retinal endothelial cell (HREC) model and a streptozotocin (STZ)-induced rat model of diabetic retinopathy.\n\nThe peptide's protective effects included reduced cell death, inhibited abnormal blood vessel tube formation, and suppressed inflammatory markers. Mechanistically, Exendin-4 downregulated TGFB2 (transforming growth factor beta-2) expression. When TGFB2 was overexpressed in cells, Exendin-4's protective effects were reversed, establishing TGFB2 as the mediating pathway.","whyItMatters":"GLP-1 agonists like exenatide (based on Exendin-4) and semaglutide are already widely prescribed for diabetes and obesity. If they also protect against diabetic retinopathy — one of diabetes' most feared complications — patients taking these drugs may get an important bonus benefit. This could influence prescribing decisions toward GLP-1 agonists for diabetic patients at risk of eye disease.","specificNumbers":"","methodology":"The study used two complementary models: (1) human retinal endothelial cells (HRECs) cultured in high-glucose conditions (in vitro), and (2) STZ-induced diabetic rats (in vivo). Techniques included qRT-PCR for gene expression, CCK-8 for cell viability, TUNEL for cell death detection, western blotting for protein levels, tube formation assays for angiogenesis, and ELISA for cytokine measurements. TGFB2 overexpression experiments confirmed the mechanism.","limitations":"The study used STZ-induced diabetes in rats, which models type 1 rather than type 2 diabetes — the form most commonly treated with GLP-1 agonists. The in vitro model used high glucose alone, which doesn't capture the full complexity of diabetic retinopathy. Specific dosing details and long-term effects were not described in the abstract. No human clinical data were presented."},{"rthcId":"RPEP-12217","title":"Abdominal massage modulates gut microbiota and brain-gut peptides in insomnia model rats.","authors":"Liu, Junchang; Aikebaier, Gulaisaer; Lu, Xusheng; Zhang, Xingping","year":2025,"journal":"Frontiers in microbiology, 16, 1720248","doi":"10.3389/fmicb.2025.1720248","pmid":"41409981","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12218","title":"Are GLP-1 receptor agonists and diabetic retinopathy foes or friends?","authors":"Liu, Kai; Liu, Shu; Wang, Dong; Qiao, Hong","year":2025,"journal":"Diabetes & metabolism, 51(6), 101696","doi":"10.1016/j.diabet.2025.101696","pmid":"40834980","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12219","title":"The clinical features and outcomes of diabetes patients infected with COVID-19: a systematic review and meta-analysis comprising 192,693 patients.","authors":"Liu, Kai; Liu, Shu; Xu, Ting-Ting; Qiao, Hong","year":2025,"journal":"Frontiers in medicine, 12, 1523139","doi":"10.3389/fmed.2025.1523139","pmid":"39944495","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12220","title":"In-vitro metabolite identification for MEDI7219, an oral GLP-1 analog, using LC-MS/MS with CID and EAD approaches.","authors":"Liu, Kate; Huang, Yue; Wang, Taoqing; Mu, Ruipeng; Rosenbaum, Anton I","year":2025,"journal":"Bioanalysis, 17(13), 881-888","doi":"10.1080/17576180.2025.2535954","pmid":"40827388","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12221","title":"Efficacy and Safety of Dulaglutide Biosimilar LY05008 Versus the Reference Product Dulaglutide (Trulicity) in Chinese Adults With Type 2 Diabetes Mellitus: A Randomized, Open-Label, Active Comparator Study.","authors":"Liu, Li; Cheng, Zhifeng; Wang, Lianwei; Zhang, Lili; Li, Shunbin; Li, Shu; Pang, Shuguang; Li, Qifu; Bian, Fang; Gu, Junling; Shen, Jie; Fu, Liujun; Sun, Baiping; Zhao, Yanyan; Dou, Changlin; Zeng, Zhaoyang; Guo, Lixin","year":2025,"journal":"Journal of diabetes, 17(4), e70077","doi":"10.1111/1753-0407.70077","pmid":"40214296","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12222","title":"The Efficacy and Safety of Tirzepatide in Patients with Diabetes and/or Obesity: Systematic Review and Meta-Analysis of Randomized Clinical Trials.","authors":"Liu, Ligang; Shi, Hekai; Xie, Merilyn; Sun, Yuxiao; Nahata, Milap C","year":2025,"journal":"Pharmaceuticals (Basel, Switzerland), 18(5)","doi":"10.3390/ph18050668","pmid":"40430487","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12223","title":"Tirzepatide vs semaglutide and liraglutide for weight loss in patients with overweight or obesity without diabetes: A short-term cost-effectiveness analysis in the United States.","authors":"Liu, Ligang; Cui, Jiayu; Neidecker, Marjorie V; Nahata, Milap C","year":2025,"journal":"Journal of managed care & specialty pharmacy, 31(5), 441-450","doi":"10.18553/jmcp.2025.31.5.441","pmid":"40298310","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12224","title":"Efficacy of Incretin-Based Therapies in Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials.","authors":"Liu, Lili; Xia, Ying; Wang, Bian; Zhang, Yiyu","year":2025,"journal":"Journal of gastroenterology and hepatology, 40(11), 2659-2673","doi":"10.1111/jgh.70084","pmid":"41025363","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 32 randomized controlled trials with 2,783 participants, GLP-1 receptor agonists were associated with resolution of metabolic dysfunction-associated steatohepatitis (MASH) without worsening fibrosis at a relative risk of 3.33 (95% CI 2.38–4.66, I²=12.9%), demonstrating remarkable consistency across studies.\n\nGLP-1 RAs reduced liver fat content by a weighted mean difference of -4.34% (95% CI -5.88 to -2.81), though with high heterogeneity (I²=95.3%). They also significantly improved liver function tests, serum triglycerides, body weight, BMI, waist circumference, and HbA1c. Gastrointestinal side effects were increased.\n\nDPP-4 inhibitors showed no significant effects on any liver or metabolic parameter except HbA1c (WMD -0.62%, 95% CI -0.91 to -0.33), establishing a clear distinction between the two incretin-based drug classes for liver disease.","whyItMatters":"MASLD/MAFLD is the most common liver disease worldwide, affecting roughly a quarter of the global population, and can progress to cirrhosis and liver cancer. Until recently, no pharmacological treatment was approved for it. This comprehensive meta-analysis of 32 RCTs provides strong evidence that GLP-1 receptor agonists not only improve liver fat and inflammation but can actually resolve steatohepatitis — the dangerous inflammatory stage — without worsening fibrosis. This supports GLP-1 drugs as a promising treatment for a disease with enormous global burden.","specificNumbers":"","methodology":"Systematic review and meta-analysis following standard methodology, searching PubMed, Cochrane Library, and EMBASE for studies published before December 2024. Included 32 randomized controlled trials with 2,783 participants with MASLD. Outcomes included liver histology, liver fat content, liver function, serum lipids, anthropometric measures, HbA1c, and gastrointestinal side effects. Results were pooled using relative risk for categorical outcomes and weighted mean differences for continuous outcomes, with heterogeneity assessed by I².","limitations":"High heterogeneity (I²=95.3%) in the liver fat content analysis suggests substantial variability across trials in study design, patient populations, specific drugs used, and treatment durations. The meta-analysis groups different GLP-1 RAs together (including single, dual, and triple agonists), which may obscure differences between individual drugs. Most trials were relatively short-term, and long-term outcomes (cirrhosis prevention, liver cancer risk) remain unknown. The increased gastrointestinal side effects may limit tolerability for some patients."},{"rthcId":"RPEP-12225","title":"The relation between tirzepatide and adverse cardiovascular events or renal adverse events: a meta-analysis based on randomized controlled trials.","authors":"Liu, Lishen; Chen, Jingqi; Zhang, Xiaoming; Zhu, Sidong; Dai, Tianfu; Wu, Qingping; Fang, Yinchao","year":2025,"journal":"Diabetology & metabolic syndrome, 18(1), 12","doi":"10.1186/s13098-025-02064-1","pmid":"41390457","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12226","title":"GLP-1 Receptor Agonists and Non-Arteritic Anterior Ischemic Optic Neuropathy: What an Endocrinologist Needs to Know.","authors":"Liu, Livia; Mohan, Sharanya; Wu, Linda","year":2025,"journal":"The Journal of clinical endocrinology and metabolism, 111(1), e308-e313","doi":"10.1210/clinem/dgaf541","pmid":"41022666","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12227","title":"Method Development of Pegmolesatide for Doping Analysis: A Novel Synthetic Erythropoietin-Mimetic Agent.","authors":"Liu, Lu; Wang, Zhanliang; Zhao, Lingyu; Zhou, Xinmiao; Zhang, Lisi","year":2025,"journal":"Drug testing and analysis, 17(11), 2210-2219","doi":"10.1002/dta.3931","pmid":"40675650","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12228","title":"β-Glucan-Modified Liposomes for Microfold Cell-Targeted Oral Delivery of Food-Derived Angiotensin I-Converting Enzyme Inhibitory Peptides Using Microfluidics.","authors":"Liu, Meijun; Qiao, Fengzhi; Wang, Shaolei; Ding, Wenhao; Xuan, Shichao; De Souza, Cristabelle; Asif Javaid, Muhammad; Zhang, Zhe; Yi, Huaxi; Zhang, Lanwei; Lin, Kai","year":2025,"journal":"Journal of agricultural and food chemistry, 73(42), 26733-26749","doi":"10.1021/acs.jafc.5c08015","pmid":"41078346","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Two egg white-derived ACE-inhibitory peptides (RADHPFL and YAEERYPIL) were encapsulated into liposomes using a controlled microfluidic self-assembly process. β-Glucan was grafted onto the liposomal surface to target intestinal M cells via the Dectin-1 receptor.\n\nEncapsulation significantly improved gastrointestinal stability of the peptides and preserved their ACE inhibitory activity compared to free peptides.\n\nIn spontaneously hypertensive rats (SHR), both single-dose and continuous administration of the β-glucan-functionalized liposomes produced superior antihypertensive effects compared to both free peptides and unmodified liposomes. The blood pressure reduction was mediated through modulation of the renin-angiotensin system, improved renal and cardiac function, and amelioration of endothelial dysfunction.","whyItMatters":"Bioactive peptides from food are an attractive alternative to pharmaceutical blood pressure drugs, but their destruction during digestion has been a major barrier. This study demonstrates that smart delivery technology — using natural materials like β-glucan to target specific gut absorption pathways — can overcome this barrier and deliver meaningful blood pressure reduction. This bridges the gap between food science and drug delivery, potentially enabling functional foods that actually work.","specificNumbers":"","methodology":"The researchers used microfluidic self-assembly to create liposomes (from lecithin, cholesterol, and DSPE-β-glucan) encapsulating two ACE-inhibitory peptides derived from egg white proteins. Gastrointestinal stability was tested in vitro using simulated digestion. M cell targeting was assessed through Dectin-1 receptor interactions and Peyer's patch uptake studies. Antihypertensive efficacy was tested in spontaneously hypertensive rats using both single-dose and continuous administration protocols, measuring blood pressure along with markers of renin-angiotensin system activity, kidney function, cardiac function, and endothelial health.","limitations":"This is an animal study in spontaneously hypertensive rats, a model that may not perfectly represent human hypertension. The complexity of the delivery system (microfluidic assembly, specialized lipid components) may make large-scale manufacturing challenging and costly. Specific blood pressure values and degree of reduction are not reported in the abstract. Long-term safety of chronic liposome ingestion is not addressed. The peptides are derived from egg white, which may be problematic for people with egg allergies. Human bioavailability and efficacy remain to be demonstrated."},{"rthcId":"RPEP-12229","title":"Sevoflurane Preconditioning Protects Against Myocardial Ischemia Reperfusion Injury in Mice via PI3K/AKT/GSK3β-mediated Upregulation of Syntaxin1a.","authors":"Liu, Meng; Xu, Fengying; Lv, Jinjin; Liu, Xiaofeng; Wang, Eerdun","year":2025,"journal":"Journal of biochemical and molecular toxicology, 39(5), e70260","doi":"10.1002/jbt.70260","pmid":"40265646","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12230","title":"Effect of desalination-related pH shift on whey protein structure and digestion: Insights from spectroscopy, molecular dynamics simulation, and peptidomics.","authors":"Liu, Meng-Qi; Chen, Yun; Zhao, Hong-Fu; Qiu, Ying-Chao; Zhang, Ying-Hua; Mu, Zhi-Shen","year":2025,"journal":"Food chemistry, 493(Pt 3), 145977","doi":"10.1016/j.foodchem.2025.145977","pmid":"40840369","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12231","title":"Multi-Omics and Network-Based Drug Repurposing for Septic Cardiomyopathy.","authors":"Liu, Pei-Pei; Yu, Xin-Yue; Pan, Qing-Qing; Ren, Jia-Jun; Han, Yu-Xuan; Zhang, Kai; Wang, Yan; Huang, Yin; Ban, Tao","year":2025,"journal":"Pharmaceuticals (Basel, Switzerland), 18(1)","doi":"10.3390/ph18010043","pmid":"39861106","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12232","title":"Clinical characteristics and prognosis of exchange transfusion in infants with severe pertussis.","authors":"Liu, Pingping; Xiao, Zhenghui; Huang, Jiaotian; Chen, Yanying; Liu, Juan","year":2025,"journal":"BMC pediatrics, 25(1), 761","doi":"10.1186/s12887-025-06132-3","pmid":"41044722","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12233","title":"Effects of warm needle acupuncture on behavioral pain threshold in a rat model of migraine.","authors":"Liu, Qiang; Qin, Xiaoguang; Luo, Chenglin; Zhao, Zhongting; Xie, Wangjun; Du, Xiaozheng; Qin, Xin","year":2025,"journal":"Frontiers in neurology, 16, 1538182","doi":"10.3389/fneur.2025.1538182","pmid":"41103513","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12234","title":"Weight loss mediates improvement in proinsulin processing during GLP-1 receptor agonist treatment.","authors":"Liu, Renjiao; Hou, Dangmin; Leng, Mingxin; Li, Zhouhuiling; Zhang, Yifang; Liu, Lingling; Wang, Xincheng; Li, Chunjun","year":2025,"journal":"Diabetology & metabolic syndrome, 17(1), 286","doi":"10.1186/s13098-025-01765-x","pmid":"40682186","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12235","title":"Semax peptide targets the μ opioid receptor gene Oprm1 to promote deubiquitination and functional recovery after spinal cord injury in female mice.","authors":"Liu, Rongjie; Chen, Yituo; Huang, Haosheng; Li, Xiang; Lv, Junlei; Jiang, Liting; Jiang, Hongyi; Wu, Chenyu; Chen, Weikai; Xu, Hongwei; Zhu, Zhefan; Cai, Haoxu; Xiao, Jian; Yin, Lihui; Ni, Wenfei","year":2025,"journal":"British journal of pharmacology, 182(22), 5489-5516","doi":"10.1111/bph.70122","pmid":"40692165","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semax improved functional recovery in a mouse spinal cord injury model, as measured by footprint analysis, Basso locomotor scores, and inclined plane tests. The mechanism was traced through a novel pathway:\n\n1. Semax targets the μ-opioid receptor (Oprm1)\n2. This regulates the ubiquitin-specific protease USP18\n3. USP18 controls deubiquitination of the FTO protein (fat mass and obesity-associated protein)\n4. This stabilizes lysosomal membranes, reducing lysosomal membrane permeabilization (LMP)\n5. Reduced LMP prevents pyroptosis (inflammatory cell death)\n\nRNA sequencing, network pharmacology, and molecular docking confirmed the μ-opioid receptor as Semax's molecular target. USP18 knockdown experiments validated its role in the pathway.","whyItMatters":"Spinal cord injury remains one of the most devastating and treatment-resistant neurological conditions. This study identifies a completely new mechanism for Semax — a peptide already used clinically in Russia for stroke — connecting it to opioid receptor signaling and lysosomal stability. The discovery that Semax prevents inflammatory cell death through this pathway suggests it could be repurposed for spinal cord injury, an indication with very few effective treatments.","specificNumbers":"","methodology":"Researchers created spinal cord injuries in female C57BL/6 mice by impact at T9-T10. Functional recovery was assessed using footprint analysis, Basso locomotor scores, inclined plane tests, and histochemistry. Molecular mechanisms were investigated using immunofluorescence, Western blot, RT-qPCR, and transmission electron microscopy in both the SCI mouse model and a PC12 cell neuroinflammation model. RNA sequencing identified differentially expressed genes, network pharmacology predicted drug targets, and molecular docking confirmed receptor binding. USP18 knockdown experiments validated the proposed mechanism.","limitations":"Only female mice were studied, and sex differences in spinal cord injury recovery are well documented. The mouse SCI model (contusion at T9-T10) represents only one type of spinal cord injury. Network pharmacology and molecular docking provide computational predictions that, while validated by knockdown experiments, may not capture the full complexity of in vivo drug-receptor interactions. Translation from mouse to human spinal cord injury has historically been very difficult."},{"rthcId":"RPEP-12236","title":"Potential of Marine Bacterial Metalloprotease A69 in the Preparation of Antarctic Krill Peptides with Multi-Bioactivities.","authors":"Liu, Rui; Cao, Wen-Jie; Zhao, Wen-Xiao; Yuan, Xiao-Jie; Zhang, Yu-Zhong; Qin, Qi-Long; Song, Xiao-Yan; Zhang, Xi-Ying; Li, Jian; Chen, Xiu-Lan; Zhang, Yu-Qiang","year":2025,"journal":"Marine drugs, 23(6)","doi":"10.3390/md23060226","pmid":"40559635","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12237","title":"Evaluating cardioprotective strategies for anthracycline-induced cardiotoxicity in breast cancer: insights from a systematic review and network meta-analysis.","authors":"Liu, Runyu; Fan, Cong; Liu, Xiaoling; Li, Mengmeng; Zhang, Yuan; Zhang, Mei","year":2025,"journal":"Cardio-oncology (London, England), 11(1), 65","doi":"10.1186/s40959-025-00332-7","pmid":"40624671","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12238","title":"Physicochemical Properties Determination of Recombinant Human Lysozyme and Its Effects on Intestinal Development in Mice.","authors":"Liu, Ruwei; An, Qin; Zou, Yunxia; Zhang, Zhuoxing; Meng, Qinyong; Yue, Wentian; Dong, Wenwen; Zhang, Yali","year":2025,"journal":"Nutrients, 17(23)","doi":"10.3390/nu17233730","pmid":"41374020","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12239","title":"Comparative efficacy of incretin drugs on glycemic control, body weight, and blood pressure in adults with overweight or obesity and with/without type 2 diabetes: a systematic review and network meta-analysis.","authors":"Liu, Song; Hu, Jiaqiang; Zhao, Chen; Liu, Hang; He, Chunyang","year":2025,"journal":"Frontiers in endocrinology, 16, 1513641","doi":"10.3389/fendo.2025.1513641","pmid":"39968298","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12240","title":"Neuropeptide Y1 receptor antagonist alleviated osteoarthritis by restoring chondrocyte autophagy through PI3K/AKT/mTOR signaling pathway.","authors":"Liu, Song; Wu, Jianqun; Lin, Yucong; Liang, Haifeng; Cai, Yu; Wang, Le; Wang, Zhao; Sang, Hongxun","year":2025,"journal":"Journal of orthopaedic translation, 55, 146-158","doi":"10.1016/j.jot.2025.08.003","pmid":"41542094","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12241","title":"Harnessing from Nature - Evolving Potential of Antimicrobial Peptide.","authors":"Liu, Songhan; HuiXin, EveliasYan; Xing, Bengang","year":2025,"journal":"Chembiochem : a European journal of chemical biology, 26(7), e202400983","doi":"10.1002/cbic.202400983","pmid":"39871592","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12242","title":"Semaglutide outperforms insulin in restoring neutrophil function against implant-related infection in diabetic and obese mice: experimental research.","authors":"Liu, Tiexin; Zhou, Lenian; Chen, Yiwei; Lin, Junqing; Zhu, Hongyi","year":2025,"journal":"International journal of surgery (London, England), 111(1), 273-282","doi":"10.1097/JS9.0000000000001896","pmid":"38935106","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12243","title":"Therapeutic Potential of the Novel GLP-1 Receptor Agonist Semaglutide in Alcohol Use Disorder.","authors":"Liu, Tingting; Shi, Fuqiang; Guo, Zhihua; Li, Hongwu; Qin, Di","year":2025,"journal":"Pharmacopsychiatry, 58(6), 255-262","doi":"10.1055/a-2550-6470","pmid":"40228539","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Preclinical studies demonstrate that semaglutide significantly reduces alcohol consumption and relapse of alcohol addiction in rats. The GLP-1 system, described as a gut-brain peptide pathway, is implicated in the neurobiology of addictive behaviors, making the GLP-1 receptor a promising therapeutic target for alcohol use disorder.\n\nThe review notes that semaglutide may be particularly effective for overweight patients with AUD, given its dual effects on metabolism and brain reward pathways. However, safety concerns include gallbladder disease and complications from delayed gastric emptying, necessitating careful evaluation before broader clinical use.","whyItMatters":"Alcohol use disorder affects millions of people worldwide, yet approved medications are few and underutilized. Repurposing semaglutide — an already approved, well-studied peptide drug — could provide a new treatment option much faster than developing a drug from scratch. The connection between gut-brain peptide signaling and addiction also opens a new frontier in understanding why people develop substance use disorders.","specificNumbers":"","methodology":"This is a review article that compiled and evaluated preclinical (animal) and clinical findings on the GLP-1 system's role in addiction and semaglutide's potential for treating alcohol use disorder. The authors also assessed the safety profile of semaglutide to inform its potential application beyond diabetes.","limitations":"The key evidence for alcohol reduction comes from rat studies, which may not fully predict human outcomes. No large-scale human clinical trials specifically testing semaglutide for AUD are reported in this review. The safety concerns (gallbladder disease, gastroparesis) could limit use in some patients. The review also notes the heterogeneity and complexity of AUD, suggesting semaglutide may not work for all patient subgroups."},{"rthcId":"RPEP-12244","title":"Shear-Electrostatic Synergistic Hydrogels with Biomimetic Microchannels for Vascularized Maxillofacial Bone Regeneration.","authors":"Liu, Wenjing; Yang, Xiaofu; Wu, Shuai; Yu, Hao; Sun, Miao; Yu, Mengfei; Chen, Si; Wang, Xu","year":2025,"journal":"ACS applied materials & interfaces, 17(46), 63057-63068","doi":"10.1021/acsami.5c15956","pmid":"41186524","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12245","title":"Antihypertensive effects and mechanisms of wheat oligopeptides in spontaneously hypertensive rats.","authors":"Liu, Wenying; Wang, Xinze; Meng, Ganlu; Yang, Chengjun; Zhang, Xinxue","year":2025,"journal":"Journal of the science of food and agriculture, 105(15), 8935-8946","doi":"10.1002/jsfa.70135","pmid":"40827468","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Wheat oligopeptides (WOPs) demonstrated potent ACE inhibitory activity, achieving 77% inhibition at 2.5 mg/mL, and produced marked reductions in systolic (SBP), diastolic (DBP), and mean arterial blood pressure (MBP) in spontaneously hypertensive rats.\n\nThe peptides worked through multiple mechanisms: activating the Nrf2/Keap1 pathway to reduce oxidative stress in kidneys and heart tissue, lowering serum levels of six inflammatory markers (TNF-α, IL-6, IL-1β, ET-1, VEGF-A, CD62E), and modulating the PI3K/AKT signaling pathway along with AT1R, ACE, and eNOS signaling proteins to protect organ tissue from hypertension-related damage.","whyItMatters":"Hypertension affects over a billion people worldwide and is a leading cause of heart disease, stroke, and kidney failure. While synthetic ACE inhibitors are effective, they carry side effects. Food-derived peptides that lower blood pressure through multiple complementary mechanisms — ACE inhibition, anti-inflammation, and antioxidant protection — could offer a gentler, more holistic approach through functional foods.","specificNumbers":"","methodology":"Wheat oligopeptides were produced by enzymatic hydrolysis of wheat protein. ACE inhibitory activity was measured in vitro. In vivo experiments used spontaneously hypertensive rats (SHRs) — a well-established animal model for essential hypertension. Blood pressure was measured over the treatment period. Kidney and heart tissues were examined for oxidative stress and inflammation markers. Signaling pathway activation was assessed through molecular analysis of relevant proteins.","limitations":"This is an animal study using a specific rat model of hypertension; results may not directly translate to humans. The exact peptide sequences responsible for the antihypertensive effects were not individually identified. Dosing, bioavailability, and long-term safety in humans have not been evaluated. No comparison with standard antihypertensive drugs was reported."},{"rthcId":"RPEP-12246","title":"Harnessing Surface Hydrophilicity of Inhalable Nanoparticles for Precision Delivery of Glucagon-like Peptide-1 Receptor Agonists or Anti-Asthmatic Therapeutics.","authors":"Liu, Xi; Zhang, Lie; Li, Sa; Xing, Liyun; Ni, Mingjie; Huang, Minyi; Huang, Yuan","year":2025,"journal":"ACS nano, 19(24), 22357-22375","doi":"10.1021/acsnano.5c05745","pmid":"40490304","tags":["glp-1-agonists"],"studyType":"animal","evidenceStrength":"preliminary","keyFinding":"By tuning the surface hydrophilicity of inhaled liposome nanoparticles, researchers achieved two distinct delivery outcomes from the same lung-based platform. Low-hydrophilic liposomes loaded with GLP-1 receptor agonists (liraglutide or semaglutide) delivered the peptides systemically into the bloodstream, producing excellent blood sugar-lowering effects in diabetic mice. High-hydrophilic liposomes loaded with budesonide stayed in the lungs longer, treating asthma while reducing dosing frequency.\n\nThe mechanism: less hydrophilic particles crossed through alveolar epithelial cells more efficiently for systemic absorption, while more hydrophilic particles resisted both cellular transport and macrophage clearance, staying in the lungs longer.","whyItMatters":"GLP-1 drugs like semaglutide and liraglutide currently require injections, which remains a barrier for many patients. Inhaled delivery through the lungs could offer a needle-free alternative with rapid absorption. This study provides a design framework for creating inhaled GLP-1 formulations by controlling nanoparticle surface properties — a significant step toward making these peptide drugs more accessible.","specificNumbers":"Liposomes with varying hydrophilicity levels tested · Liraglutide and semaglutide loaded · Type 2 diabetes mouse model · OVA-induced asthma mouse model · Reduced dosing frequency for budesonide","methodology":"Researchers created a series of liposome nanoparticles with different surface hydrophilicity levels and loaded them with either GLP-1 agonists (liraglutide/semaglutide) or budesonide (an asthma drug). These were delivered by inhalation to mice in two disease models: type 2 diabetes and allergic asthma. Systemic absorption, pulmonary residence time, blood glucose levels, asthma symptom relief, and biocompatibility were all measured. Mechanistic studies examined transcellular transport through alveolar cells and macrophage clearance.","limitations":"This is an animal study in mice — lung anatomy and physiology differ between mice and humans, and inhaled delivery scaling to human lungs is a major challenge. Long-term safety of repeated liposome inhalation was not assessed. The specific doses and blood glucose reductions are not detailed in the abstract."},{"rthcId":"RPEP-12247","title":"NaCl-Responsive Ultrashort Peptide to Trigger Self-Assembly of TPE-Capped Supramolecular Hydrogelator.","authors":"Liu, Xiangyi; Du, Lulu; Liu, Jia; Shi, Yueting; Liu, Qipeng; Xu, Ying; Xia, Yingying; Wang, Xiaiting; Ding, Dan; Li, Xingyi; Lin, Deqing","year":2025,"journal":"Biomacromolecules, 26(1), 258-265","doi":"10.1021/acs.biomac.4c01050","pmid":"39621541","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12248","title":"Acupuncture accelerates wound healing via CGRP-RAMP1-TSP1-mediated macrophage M2 polarization.","authors":"Liu, Xiaoer; Chen, Junsheng; Zou, Lingyue; Lu, Xiaohan; Zhu, Boran; Li, Jingwen; Zhu, Yuyan; Jiang, Minjiao; Peng, Rou; Guo, Yifan; Lu, Shengfeng","year":2025,"journal":"Chinese medicine, 20(1), 192","doi":"10.1186/s13020-025-01255-2","pmid":"41250153","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Daily acupuncture around full-thickness skin wounds in mice significantly improved wound closure, collagen deposition, and tissue repair quality over 10 days. The treatment enhanced M2 macrophage polarization (the healing-promoting type) within wounds, reduced systemic macrophage burden in the spleen, and lowered both local and systemic levels of the inflammatory cytokines IL-1β and IL-6.\n\nThe mechanism was identified as the CGRP-RAMP1-TSP-1 signaling pathway. Blocking this pathway with the CGRP receptor antagonist BIBN4096 abolished acupuncture's effects on macrophage reprogramming and wound healing. However, the anti-inflammatory cytokine suppression was only partially CGRP-dependent, indicating that acupuncture also works through additional neuropeptide or neuronal pathways that remain to be identified.","whyItMatters":"CGRP is one of the most abundant neuropeptides in the body, and this study provides mechanistic evidence for how nerve-derived peptide signaling can drive immune cell reprogramming to accelerate wound healing. Beyond explaining acupuncture's effects, these findings highlight CGRP as a potential therapeutic target for improving wound healing in patients with chronic or non-healing wounds.","specificNumbers":"","methodology":"Researchers created 8mm full-thickness dorsal skin wounds in C57BL/6J mice and randomized them into control and acupuncture groups. The acupuncture group received daily 20-minute manual needling at four locations around the wound for 10 days. To test CGRP's role, some mice received the CGRP receptor antagonist BIBN4096 before each treatment. Wound repair was assessed via histology (H&E and Masson's staining), macrophage polarization was measured by flow cytometry and immunofluorescence, and cytokine levels were quantified by ELISA and RT-qPCR.","limitations":"This was a mouse study using a specific wound model, and results may not directly translate to human wound healing. The acupuncture protocol was standardized for research but may differ from clinical practice. The additional non-CGRP pathways contributing to anti-inflammatory effects were not identified. Sample sizes per group were not specified in the abstract. The 10-day observation window may not capture long-term healing outcomes."},{"rthcId":"RPEP-12249","title":"Reactive oxygen species-responsive micelles targeting activated hepatic stellate cells for treating liver fibrosis.","authors":"Liu, Xin Yu; Mao, He Ying; Hu, Jun Sheng; Dou, Tong Rui; Liu, Ben Chi; Lin, Chang Xiu; Jin, Cheng-Hua; Piao, Ming Guan","year":2025,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 385, 113997","doi":"10.1016/j.jconrel.2025.113997","pmid":"40617516","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12250","title":"Dietary patterns and testosterone balance: a review of clinical data and perspectives.","authors":"Liu, Xinyi; Li, Xusheng; Cai, Dongbao; Sun, Jianxia; Bai, Weibin","year":2025,"journal":"Journal of advanced research","doi":"10.1016/j.jare.2025.11.016","pmid":"41274640","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12251","title":"Development of a potent Xenopus GLP-1-derived GLP-1/GIP/Y2 receptor tri-agonist for obesity and type 2 diabetes.","authors":"Liu, Xiyu; Gong, Binbin; Wang, Ting; Hu, Guoqiang; Han, Jing; Sun, Lidan","year":2025,"journal":"International journal of biological macromolecules, 328(Pt 1), 147553","doi":"10.1016/j.ijbiomac.2025.147553","pmid":"40935040","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12252","title":"VIPR1 induces cuproptosis and inhibits the HIF-1α pathway in colon cancer.","authors":"Liu, Xue; Lin, Ye; Zhang, Jingzhi","year":2025,"journal":"Journal of biochemical and molecular toxicology, 39(9), e70472","doi":"10.1002/jbt.70472","pmid":"40901739","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12253","title":"Effect and mechanism of Lycium barbarum polysaccharide on gastrointestinal motility in slow transit constipation.","authors":"Liu, Yan; Yang, Bo; Liu, Haiying; Guo, Liwei; Liu, Xiaoling","year":2025,"journal":"Naunyn-Schmiedeberg's archives of pharmacology, 398(3), 2923-2931","doi":"10.1007/s00210-024-03446-4","pmid":"39305326","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12254","title":"Semaglutide attenuates myocardial ischemia-reperfusion injury by inhibiting ferroptosis of cardiomyocytes via activation of PKC-S100A9 axis.","authors":"Liu, Yan; Li, Zixuan; Xu, Xinhe; Zou, Yan; Zhang, Miaomiao; Chen, Yingyu; Zhu, Wenwu; Han, Bing","year":2025,"journal":"Frontiers in pharmacology, 16, 1529652","doi":"10.3389/fphar.2025.1529652","pmid":"40183087","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In mice with myocardial ischemia-reperfusion (45 min LAD ligation + 24 h reperfusion):\n\n- Semaglutide enhanced cardiac function recovery (ultrasound assessment)\n- Reduced cardiac fibrosis (Masson's staining)\n- Mitigated oxidative stress in cardiomyocytes\n- Inhibited ferroptosis in cardiomyocytes\n- RNA sequencing identified S100A9 (S100 calcium-binding protein A9) as the target gene\n- In vitro confirmation: semaglutide activated PKC (Protein Kinase C) pathway, which decreased S100A9 expression, thereby inhibiting ferroptosis\n\nThe PKC → S100A9 → ferroptosis inhibition axis represents a novel mechanism for semaglutide's cardioprotective effects.","whyItMatters":"Heart attacks remain the leading cause of death globally, and ischemia-reperfusion injury is an unavoidable consequence of the life-saving procedure of reopening blocked arteries. There is currently no approved drug specifically targeting reperfusion injury. The discovery that semaglutide — already widely prescribed and well-characterized for safety — protects against this injury through a specific molecular pathway could lead to its use as a cardioprotective agent during heart attack intervention, without requiring development of an entirely new drug.","specificNumbers":"","methodology":"A mouse model of myocardial ischemia-reperfusion was created by ligating the left anterior descending coronary artery for 45 minutes followed by 24 hours of reperfusion. Cardiac function was assessed by small animal ultrasound; fibrosis by Masson's staining; oxidative stress and ferroptosis markers were measured in vivo. RNA sequencing was performed to identify semaglutide's target genes. The mechanism was validated in vitro by studying PKC pathway activation, S100A9 expression, and ferroptosis in cardiomyocyte cell cultures.","limitations":"The mouse ischemia-reperfusion model uses a single artery ligation, which may not perfectly replicate human heart attacks involving complex coronary anatomy and atherosclerotic disease. Semaglutide timing relative to the injury is not clearly specified — whether it was given before, during, or after ischemia matters clinically. The RNA sequencing identified S100A9 as the primary target, but other pathways may also contribute. The study did not include a survival analysis. The in vitro validation used isolated cardiomyocytes, which lack the complex multicellular environment of the heart."},{"rthcId":"RPEP-12255","title":"Oxytocin modulates inhibitory balance in the prelimbic cortex to support social memory consolidation during REM sleep.","authors":"Liu, Yan-Chao; Deng, Yu-Chen; Zhu, Zi-Tao; Rao, Bo; Shang, Hong-Lei; Wang, Li-Ke; Li, Tao; Wang, Ya-Rong; Wang, Jian-Zhi; Zhang, Qing-Ping; Gao, Yang; Xu, Hai-Bo","year":2025,"journal":"Theranostics, 15(8), 3257-3274","doi":"10.7150/thno.109104","pmid":"40093885","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12256","title":"Type 2 diabetes remission: multidimensional pharmacological strategies and future perspectives.","authors":"Liu, Yang; Gang, Xiaokun; Liu, Xinming; Jiang, Wei; Yang, Yuqi; Wang, Guixia","year":2025,"journal":"Frontiers in endocrinology, 16, 1687601","doi":"10.3389/fendo.2025.1687601","pmid":"41427055","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12257","title":"Cardiac dilation, energy stress, and ventricular remodeling: insights from prolonged voluntary exercise in male mice with TAC-induced HFpEF.","authors":"Liu, Yanna; Wang, Li; Jiao, Sirui; Yang, Xiaohan; Liu, Gang; Fan, Kai; Zhao, Henan; Ma, Jianmei","year":2025,"journal":"Journal of applied physiology (Bethesda, Md. : 1985), 138(3), 746-760","doi":"10.1152/japplphysiol.00275.2024","pmid":"39873300","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12258","title":"Self-assembled peptides derived from sesame meal as novel carriers for β-carotene with enhanced bioavailability: A study integrating experimental and computational perspectives.","authors":"Liu, Yaqi; Zhu, Zehui; Ai, Xin; Pan, Fei; Tian, Wenli; Zhao, Lei; Zhao, Liang","year":2025,"journal":"Food chemistry, 497, 147015","doi":"10.1016/j.foodchem.2025.147015","pmid":"41223530","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Sesame protein hydrolysates with 12% degree of hydrolysis (SPHDH12) formed optimal self-assembling nanoparticles for beta-carotene delivery:\n\n- Nanoparticle size: 50.30 ± 0.43 nm\n- Encapsulation efficiency: 75.23 ± 0.92%\n- Drug loading capacity: 11.14 ± 0.14%\n- Beta-carotene encapsulation caused structural shifts: 33.8% decrease in α-helix and 41.9% increase in β-sheet content\n- Peptidomics identified five core peptides responsible for self-assembly via hydrophobic interactions\n- In vitro digestion: prolonged beta-carotene release (26.76% cumulative)\n- In vivo (rats): peak plasma concentration 64.98 ng/mL, 2.73-fold higher bioavailability versus free beta-carotene","whyItMatters":"Many valuable nutrients and drug compounds are hydrophobic — they don't dissolve in water, making them difficult for the body to absorb after oral consumption. This study demonstrates that food-derived peptides — from a common and inexpensive source (sesame) — can solve this delivery problem naturally. Unlike synthetic nanocarriers, these peptides are biocompatible, biodegradable, and derived from food-grade ingredients. The 2.73-fold bioavailability improvement is substantial and could improve the effectiveness of beta-carotene supplements and potentially other fat-soluble nutrients.","specificNumbers":"","methodology":"Sesame protein was hydrolyzed with alkaline protease to produce peptide hydrolysates at 12% degree of hydrolysis. Beta-carotene was encapsulated into the self-assembled peptide nanoparticles under optimized conditions. Nanoparticle characterization included size measurement, encapsulation efficiency, and drug loading capacity. Structural changes were analyzed by FTIR spectroscopy and secondary structure analysis. Peptidomics (mass spectrometry-based peptide identification) combined with coarse-grained molecular dynamics simulations identified the core self-assembling peptides and their interaction mechanisms. In vitro simulated digestion assessed release kinetics. Rat pharmacokinetic studies measured plasma beta-carotene levels and calculated oral bioavailability.","limitations":"The study was conducted in rats, whose gastrointestinal physiology differs from humans. The 2.73-fold bioavailability improvement, while significant, still means most beta-carotene is not absorbed. The five identified core peptides need validation as the primary drivers of self-assembly. Manufacturing consistency and shelf stability of the nanoparticles were not addressed. The system was only tested with beta-carotene — applicability to other hydrophobic compounds requires separate validation. Cost comparison with existing beta-carotene formulations was not provided."},{"rthcId":"RPEP-12259","title":"Bovine Milk Casein-Derived Sleep-Enhancing Peptides: Bioavailability, Functional Mechanisms, and Development Strategies.","authors":"Liu, Yibo; Liu, Meishuai; Wang, Yuanbin; Liu, Libo; Zhang, Guofang; Li, Chun; He, Jian; Chen, Zhicheng; Su, Quan; Wei, Jiazhou","year":2025,"journal":"Journal of agricultural and food chemistry, 73(45), 28608-28623","doi":"10.1021/acs.jafc.5c09875","pmid":"41157925","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12260","title":"Ectopic fat deposition in intestinal wall caused the increase of L cell pyroptosis mainly through local hypoxia.","authors":"Liu, Yimeng; Wu, Huihui; Ma, Qianwen; Lu, Zhijin; Zhao, Pu; Li, Xiaoyu; Li, Meiyan; Wen, Jie","year":2025,"journal":"Obesity research & clinical practice, 19(6), 477-489","doi":"10.1016/j.orcp.2025.12.002","pmid":"41365764","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12261","title":"The Effects of Counter-Ions on Peptide Structure, Activity, and Applications.","authors":"Liu, Ying; Huang, Yi; Yang, Lan; Gao, Yu; Jia, Zheng; Liu, Tingting; Su, Baoling; Wang, Chuyuan; Jin, Lili; Zhang, Dianbao","year":2025,"journal":"Biomolecules, 15(11)","doi":"10.3390/biom15111567","pmid":"41301485","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12262","title":"Transcutaneous occipital nerve stimulation alleviated migraine related pain by regulating synaptic plasticity and CGRP expression in the periaqueductal gray of male rats.","authors":"Liu, Yinglu; Guo, Shengli; Li, Yang; Mao, Jingrui; Lin, Xiaoxue; Liu, Ruozhuo; Zhao, Dengfa; Dong, Zhao; Yu, Shengyuan; Han, Xun","year":2025,"journal":"The journal of headache and pain, 26(1), 61","doi":"10.1186/s10194-025-02006-2","pmid":"40155829","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12263","title":"Novel chimeric peptides of endomorphin-2 and the active fragments of ghrelin exhibit blood-brain barrier permeability and central antinociceptive effects with reduced opioid-related side effects.","authors":"Liu, Yongling; Xu, Biao; Cheng, Songxia; Wang, Yan; Ding, Jiali; Shen, Xiaoyu; Wu, Bing; Xu, Liangquan; Wei, Jie","year":2025,"journal":"Neuropharmacology, 269, 110324","doi":"10.1016/j.neuropharm.2025.110324","pmid":"39904410","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12264","title":"CKG-TPI: integrating collaborative knowledge graph with sequence interactions for TCR-peptide binding specificity.","authors":"Liu, Yue; Wang, Haoyan; Wang, Guohua; Liu, Yadong; Jiang, Tao; Wang, Yadong","year":2025,"journal":"Briefings in bioinformatics, 26(5)","doi":"10.1093/bib/bbaf486","pmid":"40977266","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12265","title":"Molecular dynamics insights into the binding interactions of semaglutide with human serum albumin.","authors":"Liu, Yueyang; Wen, Weixuan; Xu, Benao; Wang, Linwei; Zhao, Yongshan; Zhang, Jinghai","year":2025,"journal":"Journal of biomolecular structure & dynamics, 1-18","doi":"10.1080/07391102.2025.2532848","pmid":"40720332","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12266","title":"Elucidating important factors and corresponding method optimization for sensitive detection of small peptide drugs in human urine by solid-phase extraction and UPLC-HRMS: The influence of MS scan modes, protein precipitants, and ammonium formate.","authors":"Liu, Yunxi; Ma, Congcong; Dong, Tianyu; Yan, Kuan; He, Genye; Wang, Zhanliang; Zhang, Yufeng; Liu, Lu; Chang, Wei","year":2025,"journal":"Drug testing and analysis, 17(4), 457-469","doi":"10.1002/dta.3746","pmid":"38866411","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12267","title":"Subcellular Organelle Targeting as a Novel Approach to Combat Tumor Metastasis.","authors":"Liu, Zefan; Liu, Yang; Kang, Xin; Li, Lian; Xiang, Yucheng","year":2025,"journal":"Pharmaceutics, 17(2)","doi":"10.3390/pharmaceutics17020198","pmid":"40006565","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12268","title":"Antimicrobial peptide CRAMP/LL-37 mediates ferroptosis resistance in cardiomyocytes by inhibiting cathepsin L.","authors":"Liu, Zhantao; Zhang, Qingsong; Su, Dan; Chen, Hong; Wang, Bowen; Ye, Lin; Wang, Peiyan; Wu, Jingnan; Jia, Wencan; Liu, Lijun; Wang, Jianxun; Miao, Shuo","year":2025,"journal":"Basic research in cardiology, 120(5), 1011-1025","doi":"10.1007/s00395-025-01122-z","pmid":"40517353","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CRAMP levels were reduced in infarcted cardiac tissue and in cardiomyocytes exposed to ferroptosis inducers. Overexpressing CRAMP or pretreating cells with LL-37 peptide alleviated ferroptosis, while CRAMP knockdown worsened cell death. The mechanism involves CRAMP inhibiting cathepsin L (CTSL) activity, which preserves PDIA4 — a protein that suppresses ferroptosis. In the mouse myocardial infarction model, both CRAMP overexpression and direct CRAMP peptide administration significantly reduced myocardial injury and improved cardiac function.","whyItMatters":"Heart attacks remain the leading cause of death worldwide, and ferroptosis is increasingly recognized as a major driver of heart muscle loss after ischemic injury. Discovering that a natural antimicrobial peptide can protect the heart from ferroptosis opens a completely new therapeutic approach — repurposing CRAMP/LL-37 from infection defense to cardiac protection.","specificNumbers":"CRAMP reduced in infarcted tissue · overexpression alleviated ferroptosis · knockdown worsened cell death · CTSL elevated under ferroptotic stress · PDIA4 pathway identified · in vivo cardiac function improved","methodology":"Combined in vitro and in vivo study. In vitro: cardiomyocytes were treated with ferroptosis inducers, with CRAMP overexpressed or knocked down to test its role. CTSL activity and PDIA4 expression were measured. In vivo: mouse myocardial infarction model with CRAMP overexpression and CRAMP peptide administration. Protein interactions were identified using database screening.","limitations":"Preclinical mouse study — translation to human cardiac disease is uncertain. The abstract does not provide specific quantitative outcome data (e.g., infarct size reduction, ejection fraction numbers). The mechanism was primarily established in cell culture with in vivo confirmation, but the pharmacokinetics and optimal dosing of CRAMP peptide for cardiac protection were not detailed."},{"rthcId":"RPEP-12269","title":"The Clinical Application of GLP-1RAs and GLP-1/GIP Dual Receptor Agonists Based on Pharmacological Mechanisms: A Review.","authors":"Liu, Zhao; Yu, Shanshan; Jin, Xinyan; Sheng, Luguang; YanMu, Mai Re; Gao, Jie; Lu, Jun; Lei, Tao","year":2025,"journal":"Drug design, development and therapy, 19, 10383-10409","doi":"10.2147/DDDT.S559919","pmid":"41312047","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 receptor agonists work through multiple mechanisms: stimulating insulin secretion, suppressing glucagon release, delaying gastric emptying, and reducing appetite via GLP-1 receptor activation. These agents have demonstrated significant efficacy for type 2 diabetes and obesity management.\n\nDual GLP-1/GIP receptor agonists like tirzepatide activate both GLP-1 and GIP receptors simultaneously, providing enhanced glycemic control, greater weight loss, and improved metabolic function compared to single-target agents. Beyond metabolic effects, emerging evidence supports cardiovascular protection, neuroprotective benefits, and positive effects on mental health for these drug classes. The review also covers advances in triple receptor agonists targeting GLP-1, GIP, and glucagon receptors.","whyItMatters":"GLP-1-based therapies are among the most transformative drug developments of the past decade, reshaping treatment of diabetes and obesity and now expanding into cardiovascular disease, neurodegeneration, and mental health. Understanding the differences between single, dual, and emerging triple receptor agonists is critical for clinicians and patients navigating these rapidly evolving treatment options. This review provides a timely synthesis as these drugs move into clinical use for an ever-widening range of conditions.","specificNumbers":"","methodology":"This is a comprehensive narrative review that systematically compares the mechanistic pathways, therapeutic efficacy, and safety profiles of GLP-1 receptor agonists versus GLP-1/GIP dual receptor agonists. The review integrates evidence from clinical trials across multiple therapeutic areas including diabetes, obesity, cardiovascular disease, neurological conditions, perioperative management, and neuropsychiatric outcomes.","limitations":"As a narrative review, the paper reflects selective literature coverage rather than a systematic meta-analysis. The evidence for newer applications (neuroprotection, mental health, perioperative use) is still emerging and largely from early-stage or observational studies. Long-term safety data for dual and triple receptor agonists is limited. The review does not provide specific numerical comparisons between individual drugs within each class."},{"rthcId":"RPEP-12270","title":"Rate and Risk of Nonarteritic Anterior Ischemic Optic Neuropathy with Semaglutide Use for Diabetes and Weight Loss: A Systematic Review and Meta-Analysis.","authors":"Liu, Zhengyang; Raveendran, Dev; Fourlanos, Spiros; Chong, Elaine W","year":2025,"journal":"Ophthalmology","doi":"10.1016/j.ophtha.2025.12.022","pmid":"41475544","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12271","title":"GLP-1 receptor agonist protects glucose-stimulated insulin secretion in pancreatic β-cells against lipotoxicity via PPARδ/UCP2 pathway.","authors":"Liu, Zhigu; Chen, Yalan; Su, Yanna; Peng, Yueyue; Xu, Fen; Yao, Bin; Liang, Hua; Lin, Beisi; Xu, Wen","year":2025,"journal":"Cellular and molecular life sciences : CMLS, 82(1), 375","doi":"10.1007/s00018-025-05844-0","pmid":"41165809","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12272","title":"Early treatment with nootkatone prevents pressure overload-induced ventricular remodeling and heart failure.","authors":"Liu, Zhongyuan; Zhou, Zixin; Yuan, Wenjing; Li, Jiajin; Tian, Jie; Li, Mi; Quan, Junjun","year":2025,"journal":"Frontiers in pharmacology, 16, 1702627","doi":"10.3389/fphar.2025.1702627","pmid":"41684513","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12273","title":"Matrix metalloproteinase-triggered self-assembling peptides for biomedical applications.","authors":"Liu, Zhuyun; Yu, Chunlin; Li, Zhenjia; Wang, Xiaorui; Shang, Dejing; Dong, Weibing","year":2025,"journal":"Journal of materials chemistry. B, 13(28), 8298-8334","doi":"10.1039/d5tb00625b","pmid":"40553109","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Over the past decade, MMP-triggered self-assembling peptides have been successfully developed for multiple biomedical applications:\n\n1. Hydrogels: MMP-responsive peptides form hydrogels at disease sites for treating cancer, inflammation, wound healing, myocardial infarction, and central nervous system diseases.\n\n2. Nanostructures: MMPs trigger peptide assembly into nanostructures that serve as biosensors, drug delivery vehicles, and biological response modulators. Incorporating enzyme cleavage sequences allows controlled drug release.\n\n3. Smart biomaterials: These peptides function as intelligent biomaterials — they sense the disease environment (elevated MMP levels), activate at the target site, deliver therapeutic cargo, and modulate biological responses, all triggered by the same disease-associated enzymes.","whyItMatters":"One of the biggest challenges in medicine is getting drugs to work at disease sites without affecting healthy tissue. MMP-triggered self-assembling peptides solve this elegantly — they're programmed to activate only where disease is present (signaled by elevated MMP levels). This approach could transform how we deliver cancer drugs, heal wounds, repair hearts after heart attacks, and engineer replacement tissues. It represents a convergence of peptide chemistry, smart materials, and precision medicine.","specificNumbers":"","methodology":"Comprehensive review covering the past decade of research on MMP-triggered self-assembling peptide systems. The authors surveyed studies on peptide hydrogels and nanostructures, organizing the literature by application area (cancer, inflammation, wound healing, cardiac repair, CNS disease, tissue engineering) and by functional mechanism (sensing, controlled release, targeted delivery, structural transformation).","limitations":"As a review paper, the authors present a curated view of the field's successes. Most applications described are still at the preclinical stage. Translating self-assembling peptide systems to clinical use faces challenges including manufacturing scale-up, regulatory approval for complex biomaterials, long-term stability, and potential immunogenicity. The specificity of MMP triggering may be limited since multiple MMPs are elevated in various conditions."},{"rthcId":"RPEP-12274","title":"Cost-effectiveness of Semaglutide Compared With Other Glucose-Lowering Medications in Treating Type 2 Diabetes: A Comprehensive Systematic Review and Meta-analysis.","authors":"Liu, Ziyun; Zeng, Baoqi; Sun, Feng; Xia, Qing","year":2025,"journal":"Diabetes care, 48(6), 1032-1041","doi":"10.2337/dc24-2241","pmid":"40392993","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 45 articles containing 119 comparisons, semaglutide was dominant or cost-effective in 73.9% of all analyses against within-study willingness-to-pay thresholds. However, sponsor type dramatically influenced results:\n\n- **Novo Nordisk-sponsored**: 100% found semaglutide dominant/cost-effective\n- **Non-industry sponsored**: 50% found semaglutide cost-effective\n- **Other industry sponsors**: 0% found semaglutide cost-effective\n\nSemaglutide was more likely to appear cost-effective in high-income countries, studies with longer time horizons, broader perspectives, and lower discount rates. Results remained consistent when converted to a common US$50,000/QALY willingness-to-pay threshold.","whyItMatters":"With semaglutide becoming one of the most prescribed and expensive drugs globally, understanding its true cost-effectiveness is critical for healthcare systems. The striking difference between industry-funded and independent analyses reveals how modeling choices — time horizon, perspective, discount rate — can be tuned to produce favorable results. This finding has implications not just for semaglutide but for how we evaluate the economic value of all expensive peptide-based therapeutics.","specificNumbers":"","methodology":"Systematic review and meta-analysis searching PubMed, Embase, and the Cost-Effectiveness Analysis Registry through June 2024. Included 45 articles (119 comparisons) from Europe (24), North America (13), and Asia (8). Extracted lifetime costs and quality-adjusted life-years (QALYs). Calculated proportions for cost-effectiveness outcomes and performed subgroup analyses by region, sponsor type, comparator type, and model assumptions. Reporting quality was assessed (86.7% high quality). Nearly 69% of studies were industry-sponsored.","limitations":"Cost-effectiveness analyses inherently rely on modeling assumptions that can significantly influence outcomes — the wide variation by sponsor type may partly reflect legitimate differences in model design rather than pure bias. The review couldn't access proprietary model details to assess exactly which assumptions drove differences. Regional economic variations make direct cross-country comparisons challenging. Most studies used a lifetime horizon (93.3%), which involves significant extrapolation beyond available clinical data. The analysis focused on diabetes, not obesity indications where cost-effectiveness may differ."},{"rthcId":"RPEP-12275","title":"The Impact of Glucagon-like Peptide-1 Receptor Agonists on Cardiovascular-Kidney-Metabolic Health in Romanian Patients with Type 2 Diabetes: A Retrospective Study.","authors":"Lixandru, Niculina; Gaita, Laura; Popescu, Simona; Herascu, Andreea; Timar, Bogdan; Timar, Romulus","year":2025,"journal":"Journal of clinical medicine, 15(1)","doi":"10.3390/jcm15010152","pmid":"41517401","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12276","title":"Non-Arteritic Anterior Ischemic Optic Neuropathy in an Otherwise Healthy Young Adult Patient Treated with Liraglutide and Semaglutide for Weight Loss: A Cautionary Tale.","authors":"Lixi, Filippo; Calabresi, Valerio; Cukurova, Feyza; Giannaccare, Giuseppe","year":2025,"journal":"International medical case reports journal, 18, 991-995","doi":"10.2147/IMCRJ.S531930","pmid":"40800673","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A 47-year-old Caucasian female (BMI 27.92) with no systemic risk factors developed progressive NAION one month after initiating liraglutide therapy for weight loss. Initial presentation showed BCVA of 20/40 with optic nerve head swelling and inferior visual field defects. Despite oral corticosteroid treatment (discontinued due to poor glycemic control), the condition progressed.\n\nAfter three months, she was switched to semaglutide due to poor weight loss results. Eight months later, vision had deteriorated to 20/400 with persistent ONH edema confirmed on OCT and worsened visual field defects. Given the absence of any anatomical or systemic risk factors, NAION was attributed to GLP-1 receptor agonist therapy, with liraglutide as the likely initial trigger and semaglutide as a contributing factor in progression.","whyItMatters":"As GLP-1 receptor agonists become the most widely prescribed medications for weight loss — often in relatively healthy patients with modest obesity — rare but serious adverse effects become critically important. NAION causes permanent vision loss, and this case occurred in a patient without any of the traditional risk factors (diabetes, hypertension, cardiovascular disease). The close temporal correlation and absence of alternative explanations raise an important safety signal for the millions of people using these peptide drugs.","specificNumbers":"","methodology":"This is a clinical case report of a single patient. The diagnostic workup included best-corrected visual acuity testing, optic nerve head examination, Humphrey Visual Field testing, and optical coherence tomography (OCT) at multiple time points. The temporal relationship between drug initiation and symptom onset, combined with the absence of typical NAION risk factors, formed the basis for the causation assessment.","limitations":"This is a single case report, which is the lowest level of clinical evidence and cannot establish causation. NAION can occur spontaneously, and the temporal association with GLP-1 therapy may be coincidental. The patient's optic disc anatomy (disc-at-risk phenotype) was not specifically assessed, which is a major predisposing factor for NAION. Without a control group or large-scale epidemiological data, the true risk attributable to GLP-1 agonists remains uncertain."},{"rthcId":"RPEP-12277","title":"The perinatal llama immersed in the thin oxygen of the Andean Altiplano.","authors":"Llanos, Anibal J; Herrera, Emilio A; Reyes, Victor R; Ebensperger, German; Giussani, Dino A","year":2025,"journal":"Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 380(1933), 20240180","doi":"10.1098/rstb.2024.0180","pmid":"40836812","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12278","title":"Targeting Sarcopenia in CKD: The Emerging Role of GLP-1 Receptor Agonists.","authors":"Llinares-Arvelo, Vicente; Martínez-Alberto, Carlos E; González-Luis, Ainhoa; Macía-Heras, Manuel; Siverio-Morales, Orlando; Navarro-González, Juan F; Donate-Correa, Javier","year":2025,"journal":"International journal of molecular sciences, 26(16)","doi":"10.3390/ijms26168096","pmid":"40869417","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12279","title":"Role of Glucagon-like Peptide-1 Receptor Agonists (GLP-1RAs) in Patients with Chronic Heart Failure.","authors":"Llongueras-Espí, Pasqual; García-Romero, Elena; Comín-Colet, Josep; González-Costello, José","year":2025,"journal":"Biomolecules, 15(9)","doi":"10.3390/biom15091342","pmid":"41008649","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12280","title":"No Increase in Blood Pressure Assessed With the 24-h Holter Monitoring in Patients With Episodic Migraine During Early Treatment With Anti-CGRP Monoclonal Antibodies: A Prospective Observational Study (SAFHYPER).","authors":"Lo Castro, Flavia; Bonini, Niccolò; Iannone, Luigi Francesco; Boccalini, Alberto; Brovia, Daria; Pani, Luca; Boriani, Giuseppe; Guerzoni, Simona","year":2025,"journal":"European journal of neurology, 32(9), e70351","doi":"10.1111/ene.70351","pmid":"40913367","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12281","title":"Hydroxyapatite Scaffold and Bioactive Factor Combination as a Tool to Improve Osteogenesis, In Vitro and In Vivo Experiments Using Phage Display Technology.","authors":"Lo Furno, Debora; Romano, Ivana R; Russo, Vincenzo; Rizzo, Maria Giovanna; Mannino, Giuliana; Calabrese, Giovanna; Giuffrida, Rosario; D'Aprile, Simona; Salvatorelli, Lucia; Magro, Gaetano; Bendoni, Riccardo; Dolcini, Laura; Zappalà, Agata; Guglielmino, Salvatore P P; Conoci, Sabrina; Parenti, Rosalba","year":2025,"journal":"International journal of molecular sciences, 26(15)","doi":"10.3390/ijms26157040","pmid":"40806172","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12282","title":"Echocardiography of the right heart in pulmonary arterial hypertension: insights from the ULTRA RIGHT VALUE study.","authors":"Lo Giudice, Francesco; Escribano-Subias, Pilar; Tello, Khodr; Kopec, Grzegorz; Ghio, Stefano; Giannakoulas, George; D'Alto, Michele; Filomena, Domenico; Manzi, Giovanna; Orlando, Antonio; Greco, Alessandra; Recchioni, Tommaso; Yildiz, Selin; López-Guarch, Carmen Jiménez; Cruz-Utrilla, Alejandro; Psochias, Polykarpos; Patsiou, Vasiliki; Stępniewski, Jakub; Jonas, Kamil; Scelsi, Laura; Kremer, Nils; Vergara, Andrea; Vizza, Carmine Dario; Naeije, Robert; Badagliacca, Roberto","year":2025,"journal":"European heart journal. Imaging methods and practice, 3(1), qyae121","doi":"10.1093/ehjimp/qyae121","pmid":"39816928","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12283","title":"Glycemic variability and entero-pancreatic hormones signatures after different bariatric surgery procedures: a cross-sectional study.","authors":"Lobato, Carolina B; Pereira, Sofia S; Guimarães, Marta; Soares, Bruno; Hartmann, Bolette; Nora, Mário; Holst, Jens J; Monteiro, Mariana P","year":2025,"journal":"International journal of obesity (2005), 49(10), 2042-2050","doi":"10.1038/s41366-025-01865-8","pmid":"40783465","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12284","title":"A randomized, double-blind, placebo-controlled trial of weight loss using liraglutide 3.0 mg for weight recurrence after Roux-en-Y gastric bypass.","authors":"Lofton, Holly F; Maranga, Gabrielle; Hold, Robert; Fielding, George; Youn, Heekoung; Gujral, Akash; Heffron, Sean; Fielding, Christine","year":2025,"journal":"Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery, 21(2), 135-145","doi":"10.1016/j.soard.2024.08.037","pmid":"39401933","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12285","title":"Microplastics affect food intake and the expression of appetite regulators and nutrient transporters in pond loach (Misgurnus anguillicaudatus).","authors":"Loganathan, Thanushanthahi; Dyke, Julianna; Volkoff, Helene","year":2025,"journal":"Comparative biochemistry and physiology. Part A, Molecular & integrative physiology, 310, 111935","doi":"10.1016/j.cbpa.2025.111935","pmid":"41015078","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12286","title":"Impact of stereochemical replacement on activity and selectivity of membrane-active antibacterial and antifungal cyclic peptides.","authors":"Lohan, Sandeep; Konshina, Anastasia G; Mohammed, Eman H M; Helmy, Naiera M; Jha, Srishhti K; Tiwari, Rakesh Kumar; Maslennikov, Innokentiy; Efremov, Roman G; Parang, Keykavous","year":2025,"journal":"npj antimicrobials and resistance, 3(1), 56","doi":"10.1038/s44259-025-00121-3","pmid":"40527928","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12287","title":"In the era of monoclonal antibodies targeting the calcitonin gene-related peptide pathway, is it still necessary to stop taking excessive pain medication?","authors":"Londero, Renata Gomes","year":2025,"journal":"Arquivos de neuro-psiquiatria, 83(9), 1-2","doi":"10.1055/s-0045-1809333","pmid":"40720968","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12288","title":"Adrenocortical Carcinoma With 2 Distinct Syndromes From Secretion of Insulin-Like Growth Factor 2 and Steroid Hormones.","authors":"Lonergan, Eibhlín Marie; Tan, Lok Yi Joyce; O'Sullivan, Adrian; Kanazaki, Keizo; Morita, Miwa; O'Halloran, Domhnall","year":2025,"journal":"JCEM case reports, 3(6), luaf078","doi":"10.1210/jcemcr/luaf078","pmid":"40270996","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The patient had an IGF-2:IGF-1 ratio of 60.7 (normal <10) with low insulin and C-peptide levels, confirming non-islet cell tumor hypoglycemia caused by the adrenal mass. Symptomatic hypoglycemia developed within 5 hours of a supervised fast. The tumor also caused biochemical hyperandrogenism with elevated testosterone, estradiol, and adrenal androgens, leading to endometrial hyperplasia and postmenopausal bleeding.\n\nPostoperative pathology confirmed adrenocortical carcinoma with a Ki67 proliferation index of 12% and positive immunostaining for IGF-2, providing direct histological evidence that the tumor was producing this peptide growth factor.","whyItMatters":"This case highlights how a single tumor can produce both peptide factors and steroid hormones simultaneously, creating two distinct clinical syndromes that might seem unrelated. Recognizing IGF-2-mediated hypoglycemia is critical because it requires different management than insulin-driven low blood sugar, and the underlying cause is a malignancy that needs surgical treatment.","specificNumbers":"","methodology":"This was a clinical case report of a single 59-year-old female patient. Doctors used blood tests during a supervised fasting protocol to measure IGF-2, IGF-1, insulin, and C-peptide levels. Cross-sectional imaging identified the adrenal mass, and after surgical removal, pathology and immunostaining confirmed the diagnosis.","limitations":"As a single case report, these findings cannot be generalized to other patients. There is no long-term follow-up data reported, and the mechanisms behind dual peptide and steroid secretion from one tumor are not fully explored."},{"rthcId":"RPEP-12289","title":"E7 peptide and magnesium oxide-functionalized coaxial fibre membranes enhance the recruitment of bone marrow mesenchymal stem cells and promote bone regeneration.","authors":"Long, Shengyu; Wang, Wentong; Chen, Yongcheng; Wang, Zhihua; Duan, Hao; Yuan, Ping; Xu, Yunrong; Li, Denghui; Zhang, Wan; Wang, Weizhou; He, Fei","year":2025,"journal":"BMC biotechnology, 25(1), 80","doi":"10.1186/s12896-025-01017-w","pmid":"40783756","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12290","title":"Secretory Production of Heterologous Antimicrobial Peptides in Corynebacterium glutamicum.","authors":"Long, Wei; Apitius, Lina; Lenz, Patrick; Jakob, Felix; Ruff, Anna Joёlle; Schwaneberg, Ulrich","year":2025,"journal":"Engineering in life sciences, 25(2), e70008","doi":"10.1002/elsc.70008","pmid":"39974332","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12291","title":"Combination metformin and liraglutide in PCOS: clinical efficacy in women and preclinical insights from gut microbiome modulation in rats.","authors":"Long, Xue-Feng; Fang, Yu-Qing; Li, Yan-Hui; Li, Jing-Yi; Wang, Xiu-Ping; Wang, Xiao-Li; Zhang, Ling; Liu, Yi","year":2025,"journal":"Frontiers in endocrinology, 16, 1599879","doi":"10.3389/fendo.2025.1599879","pmid":"41384017","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12292","title":"Body composition changes during weight reduction with tirzepatide in the SURMOUNT-1 study of adults with obesity or overweight.","authors":"Look, Michelle; Dunn, Julia P; Kushner, Robert F; Cao, Dachuang; Harris, Charles; Gibble, Theresa Hunter; Stefanski, Adam; Griffin, Ryan","year":2025,"journal":"Diabetes, obesity & metabolism, 27(5), 2720-2729","doi":"10.1111/dom.16275","pmid":"39996356","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tirzepatide produced a 21.3% reduction in total body weight at 72 weeks, composed of a 33.9% loss in fat mass and a 10.9% loss in lean mass. In the placebo group, these figures were 5.3%, 8.2%, and 2.6% respectively (p < 0.001 for all comparisons).\n\nCritically, the composition of weight lost was approximately 75% fat mass and 25% lean mass in both the tirzepatide and placebo groups. This ratio remained consistent across subgroups defined by sex, age, baseline BMI, and baseline fat mass.","whyItMatters":"A major concern with GLP-1 and dual-agonist weight loss drugs is that people may lose too much muscle along with fat. This study provides reassurance that tirzepatide's weight loss follows the typical biological pattern — about three-quarters fat, one-quarter lean mass — rather than causing disproportionate muscle wasting. The consistency of this ratio across subgroups strengthens the finding.","specificNumbers":"","methodology":"This was a substudy of 160 participants from the larger SURMOUNT-1 randomized controlled trial (2,539 total). Participants had obesity or overweight and underwent dual-energy X-ray absorptiometry (DXA) body scans at baseline and at week 72. Results were pooled across tirzepatide doses (5, 10, and 15 mg) and compared with placebo. Post hoc subgroup analyses examined consistency across sex, age, BMI, and baseline fat mass categories.","limitations":"The substudy included only 160 of the 2,539 SURMOUNT-1 participants, which may not be fully representative. Tirzepatide doses were pooled, so dose-specific effects on body composition could not be assessed. The study did not evaluate whether lean mass loss impacted physical function, strength, or metabolic rate. DXA measures total lean mass, which includes water and organs — not just skeletal muscle."},{"rthcId":"RPEP-12293","title":"Unanticipated Residual Gastric Contents in an Appropriately Fasted Pediatric Patient on Glucagon-Like Peptide-1 Receptor Agonist Therapy: A Case Report and Review of Perioperative Considerations.","authors":"Lookabaugh, Max; Strupp, Kim M; Webb, Leah","year":2025,"journal":"Cureus, 17(12), e99731","doi":"10.7759/cureus.99731","pmid":"41573454","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12294","title":"What's a migraine day? Analysis of the variety in the definition of a migraine day across phase III trials with drugs targeting the CGRP pathway.","authors":"Loose, Luna De; Paemeleire, Koen; Goadsby, Peter J; MaassenVanDenBrink, Antoinette; Versijpt, Jan","year":2025,"journal":"Cephalalgia : an international journal of headache, 45(11), 3331024251393986","doi":"10.1177/03331024251393986","pmid":"41190900","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12295","title":"An Integrative Review of Potential Diagnostic Biomarkers for Complex Regional Pain Syndrome.","authors":"Lopes, Revelino; Santos, André; Gomes, Teresa; Ribeiro, Júlia; Rodrigues, Ivone; Paiva, Bruno; Nzwalo, Isa; Catamo, Deise; Baco, Jamal; Buque, Helena; Botelho, Marta; Pais, Sandra; Nzwalo, Hipólito","year":2025,"journal":"Journal of clinical medicine, 14(11)","doi":"10.3390/jcm14113751","pmid":"40507512","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12296","title":"The Short and Sweet on Sodium-Glucose Cotransporter Inhibitors and Glucagon-like Peptide-1 Receptor Agonists in Heart Failure.","authors":"Lopez, Jose; Makuvire, Tracy; Davis, Jonathan D; Carbone, Salvatore","year":2025,"journal":"US cardiology, 19, e12","doi":"10.15420/usc.2024.44","pmid":"40458830","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12297","title":"A Multicenter, Open-Label Study of Combined Poly-L-Lactic Acid and Hyaluronic Midface Filler Regimen Enhances Facial Harmony and Skin Quality in GLP-1 Medication Users.","authors":"Lorenc, Z Paul; Somenek, Michael; Nguyen, Thu Q; Garimella, Sindhu; Hicks, Jessica; Le, Jennifer H T D; Meckfessel, Matthew H","year":2025,"journal":"Aesthetic surgery journal","doi":"10.1093/asj/sjaf240","pmid":"41243519","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12298","title":"Nonmechanical Small Bowel Obstruction in a Patient on Zepbound Without a Surgical History: A Case Report.","authors":"Lorenz, Nicholas; Stauffer, John; Abouafech, Alex; Mourad, Amia; Bray, Kelvin","year":2025,"journal":"Cureus, 17(8), e90657","doi":"10.7759/cureus.90657","pmid":"40978855","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12299","title":"CGRP Suppresses Protective SiglecFhi Neutrophil Development in Neonatal Group B Streptococcus Pneumonia.","authors":"Lorga, Inês; Teixeira, Ana Sofia; Carvalho, Bárbara; Soares, Joana; Ribeiro, Nuno; Cardoso, Marcos S; Cunha, Joana; Santos, Joana; Silva, Regina A; Vilanova, Manuel; Bonifácio Andrade, Elva","year":2025,"journal":"Microorganisms, 13(9)","doi":"10.3390/microorganisms13092119","pmid":"41011451","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In a neonatal mouse model of GBS pneumonia, neutrophils were recruited to infected lungs but their phenotype differed based on disease severity. Pups with moderate disease developed SiglecFhi neutrophils — a phenotype with enhanced phagocytic capacity and superior bacterial clearance. Pups with severe disease failed to develop this protective neutrophil type.\n\nThe key difference was CGRP: severely affected pups showed increased CGRP expression in the lungs. CGRP directly suppressed neutrophil activation into the SiglecFhi phenotype, limiting their antibacterial function. This represents a neuroimmune axis that GBS exploits to evade host immunity — the bacteria essentially co-opt a neural signaling molecule to shut down the most effective form of immune defense.","whyItMatters":"Neonatal GBS infection is a leading cause of newborn mortality worldwide. Understanding why some babies develop severe disease while others fight off the infection is critical for developing better treatments. This study identifies CGRP as a key immunosuppressive factor — and since CGRP-blocking drugs already exist (they're used for migraines), there's an immediate therapeutic hypothesis: could CGRP antagonists help newborns fight GBS pneumonia?","specificNumbers":"","methodology":"Researchers used a clinically relevant neonatal mouse model of GBS pneumonia. Immune cell infiltration and phenotyping (including SiglecF expression on neutrophils) were analyzed in infected neonatal lungs using flow cytometry. Disease severity was correlated with neutrophil phenotype and CGRP expression levels. The direct effect of CGRP on neutrophil activation was tested to establish the mechanistic link between CGRP levels and suppressed SiglecFhi development.","limitations":"This is a mouse model study, and neonatal immune responses differ significantly between mice and human newborns. Whether CGRP plays the same immunosuppressive role in human neonatal GBS infection is unknown. The study did not test whether CGRP-blocking drugs could improve outcomes in the infection model. The mechanisms by which GBS triggers increased CGRP production in the lungs were not fully elucidated. Sample sizes for the neonatal mouse experiments were not reported in the abstract."},{"rthcId":"RPEP-12300","title":"Experimental and Computational Study of Injectable Iron(III)/Ultrashort Peptide Hydrogels: A Candidate for Ferroptosis-Induced Treatment of Bacterial Infections.","authors":"Loth, Capucine; Barbault, Florent; Guégan, Cécile; Lemaire, Flora; Contal, Christophe; Carvalho, Alain; Hellé, Sophie; Champion, Marie; Kerdjoudj, Halima; Chan-Seng, Delphine; Ploux, Lydie; Boulmedais, Fouzia","year":2025,"journal":"Small science, 5(6), 2400618","doi":"10.1002/smsc.202400618","pmid":"40529877","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12301","title":"Cellular effects of oral egg yolk immunoglobulin-based supplementation at birth on promoting growth and strengthening intestinal mucosal innate immunity in pre-weaned piglets.","authors":"Lothong, Muttarin; Kayan, Autchara; Malison, Manmueang; Rakarcheep, Dran; Samritwatchasai, Theerawat; Thammacharoen, Sumpun; Deachapunya, Chatsri; Poonyachoti, Sutthasinee","year":2025,"journal":"Frontiers in veterinary science, 12, 1458279","doi":"10.3389/fvets.2025.1458279","pmid":"40740302","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12302","title":"GLP-1 and Its Role in Glycogen Production: A Narrative Review.","authors":"Lotosky, Joseph; Jean, Xavier; Altankhuyag, Anungoo; Khan, Saqib; Bernotas, Ashley; Sharafshah, Alireza; Blum, Kenneth; Posner, Alan; Thanos, Panayotis K","year":2025,"journal":"Biomedicines, 13(7)","doi":"10.3390/biomedicines13071610","pmid":"40722684","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12303","title":"Predicting Distribution Coefficients (LogD) of Cyclic Peptides Using Molecular Dynamics Simulations.","authors":"Lou, Hao; Feng, Mei; Al-Tamimi, Zahraa; Kuczera, Krzysztof; Hageman, Michael J","year":2025,"journal":"Pharmaceutical research, 42(4), 613-622","doi":"10.1007/s11095-025-03850-2","pmid":"40140127","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12304","title":"The Impact of New Weight-Loss Medications on Bariatric Surgery and Surgeon Employment.","authors":"Louis, Mena; Velazquez, Eric","year":2025,"journal":"Cureus, 17(5), e83903","doi":"10.7759/cureus.83903","pmid":"40497223","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12305","title":"A novel gene therapy platform for the treatment of type 2 diabetes and obesity.","authors":"Lourie, Jared; Goraltchouk, Alex; Hollander, Judith M; Berger, Nicolas J; Rosen, H Grace; Fujishiro, Atsutaro A; Luppino, Francesco; Seregin, Alexey; Rhym, Luke; Zou, Kai","year":2025,"journal":"Molecular therapy. Nucleic acids, 36(4), 102739","doi":"10.1016/j.omtn.2025.102739","pmid":"41216426","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The subcutaneously injected lipid nanoparticle-DNA system successfully expressed both exendin-4 (EX4) and a modified natural GLP-1 peptide in obese diabetic mice. Key outcomes included sustained weight loss, decreased food intake, reduced insulin resistance, and improved glycemic control. The transgene expression remained localized to the subcutaneous injection site for over 6 months — a critical safety feature ensuring the therapy doesn't spread systemically.\n\nTranscriptomic analysis confirmed that efficacy was mediated through the GLP-1 receptor pathway, validating the mechanism. Blood-based biomarkers of liver function, pancreatic function, systemic inflammation, and muscle injury were all normal, confirming systemic tolerability. The steady-state peptide production avoids the pharmacokinetic spikes from repeated injections that cause GI side effects and contribute to the ~70% one-year discontinuation rate of current GLP-1 therapies.","whyItMatters":"The GLP-1 drug market exceeds $50 billion, but patient adherence is a major problem — nearly 70% of patients discontinue within a year due to side effects and injection burden. A one-time gene therapy that provides steady, localized GLP-1 production for months could transform chronic disease management for diabetes and obesity. By avoiding the peak-and-trough drug levels of weekly injections, this approach may eliminate the nausea that drives most discontinuations while maintaining therapeutic efficacy.","specificNumbers":"","methodology":"Researchers developed a lipid nanoparticle (LNP)-based DNA delivery system encoding either exendin-4 or a modified GLP-1 peptide. The LNPs were administered via a single subcutaneous injection in obese diabetic mice (diet-induced obesity model). Efficacy was assessed through body weight, food intake, insulin resistance, and glycemic control measurements. Safety was monitored via blood biomarkers for liver function, pancreatic function, inflammation, and muscle injury. Transgene localization was tracked over 6 months. Transcriptomic profiling was performed to confirm the mechanism of action.","limitations":"This is a preclinical mouse study, and translation to humans faces significant challenges including immune responses to lipid nanoparticles, potential for uncontrolled or variable expression levels, and regulatory hurdles for gene therapy in chronic metabolic diseases (where the risk-benefit calculus is less clear than in genetic disorders). The inability to easily titrate dose or stop therapy is a concern if adverse effects emerge. Six months in mice does not directly translate to human duration. The study used a specific obesity/diabetes mouse model that may not fully replicate human metabolic disease."},{"rthcId":"RPEP-12306","title":"Euglycemic Ketoacidosis Following Coadministration of an SGLT2 Inhibitor and Tirzepatide.","authors":"Louwagie, Eli J; Diego, Jessica N; Farooqi, Crystal S; Kamal, Madiha M","year":2025,"journal":"JCEM case reports, 3(3), luaf028","doi":"10.1210/jcemcr/luaf028","pmid":"39949871","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12307","title":"Regulatory mechanism of ghrelin on testosterone secretion in type 1 diabetic rats.","authors":"Lu, Chien-Chen; Chang, Chia-Hsin; Chou, Jou-Chun; Yu, Po-Ling; Wang, Paulus S","year":2025,"journal":"Reproduction & fertility, 6(3)","doi":"10.1530/RAF-24-0087","pmid":"40601674","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12308","title":"Periovulatory neurohormone dynamics reveal an association between secretoneurin and GnRH across the mouse estrous cycle.","authors":"Lu, Chunyu; Peng, Di; Smith, Kevin B; Uju, Chinelo; Unniappan, Suraj; Duarte-Guterman, Paula; Ismail, Nafissa; Trudeau, Vance L","year":2025,"journal":"Frontiers in endocrinology, 16, 1708570","doi":"10.3389/fendo.2025.1708570","pmid":"41659333","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12309","title":"Global spinal cord peptidome profiling in response to osteoarthritis in rats.","authors":"Lu, Gaoyuan; Frézier, Marilyn; Otis, Colombe; Tran, Vu Ngoc Huong; Lussier, Bertrand; Saint-Jean, Guillaume; Beaudry, Helene; Troncy, Eric; Li, Lingjun","year":2025,"journal":"Molecular omics, 21(6), 645-656","doi":"10.1039/d5mo00152h","pmid":"41159712","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12310","title":"Structural basis of modified ligand selectivity from N-terminal PAC1R alternative splicing.","authors":"Lu, Jessica J; Deganutti, Giuseppe; Li, Miaomiao; Humphrys, Laura J; Li, Yandi; Nettleton, Theodore J; Venugopal, Hariprasad; Julita, Villy; Christopoulos, George; Reynolds, Christopher A; Sexton, Patrick M; Wootten, Denise; Zhao, Peishen; Piper, Sarah J","year":2025,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 122(47), e2521157122","doi":"10.1073/pnas.2521157122","pmid":"41264251","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12311","title":"The effects of GLP-1 receptor agonists on body composition in patients with type 2 diabetes, overweight or obesity: A meta-analysis of randomized controlled trials.","authors":"Lu, Jieying; Zou, Shen; Liu, Xinyi; Wong, Ting Yat Patrick; Zhang, Xiaomin; Xu, Ka Shing; Zhao, Yanchen; Hong, Yuanjia; Cen, Aiying; Wang, Yingxue","year":2025,"journal":"European journal of pharmacology, 1003, 177885","doi":"10.1016/j.ejphar.2025.177885","pmid":"40615102","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12312","title":"A novel Toll-like receptor in Hyriopsis cumingii responds to Aeromonas veronii GL1 infection by the MyD88 signaling pathway.","authors":"Lu, Junyi; Yang, Qinglin; Wang, Tao; He, Guihong; Yu, Xiaobo; Wu, Zhengli; Li, Yanhong","year":2025,"journal":"Fish & shellfish immunology, 166, 110597","doi":"10.1016/j.fsi.2025.110597","pmid":"40721122","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12313","title":"Alkaline Phosphatase-Triggered Spatiotemporal Repair of Corneal Injury with TB500 Peptide Hydrogel.","authors":"Lu, Ping; Shan, Mengyuan; Peng, Caihong; Ji, Wenxuan; Yang, Ting; Yang, Zhimou; Zhang, Zhuhong; Wang, Yan","year":2025,"journal":"ACS applied materials & interfaces, 17(50), 67503-67518","doi":"10.1021/acsami.5c14652","pmid":"41359360","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12314","title":"Efficacy and safety of Dengzhan Shengmai capsule in the treatment of chronic heart failure: a systematic review and meta-analysis.","authors":"Lu, Shenghua; Yu, Yunfeng; Dai, Sisi; Hu, Yaqi; He, Qin; Liu, Rongzhen; Liu, Jianhe","year":2025,"journal":"Frontiers in cardiovascular medicine, 12, 1385061","doi":"10.3389/fcvm.2025.1385061","pmid":"40060965","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12315","title":"Neuropsychiatric adverse events associated with Glucagon-like peptide-1 receptor agonists: a pharmacovigilance analysis of the FDA Adverse Event Reporting System database.","authors":"Lu, Wenchao; Wang, Shihan; Tang, Huilin; Yuan, Tao; Zuo, Wei; Liu, Yuling","year":2025,"journal":"European psychiatry : the journal of the Association of European Psychiatrists, 68(1), e20","doi":"10.1192/j.eurpsy.2024.1803","pmid":"39901452","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12316","title":"Effects of WN1703 on Cardiovascular Function in Chronic Hyperuricemia Rats and Myocardial Injury Mechanism Exploration in H9C2 Cells.","authors":"Lu, Xiaodan; Liu, Fuyao; Chen, Hongming; Cai, Haojie; Zhang, Lei; Li, Jing","year":2025,"journal":"Journal of applied toxicology : JAT, 45(3), 418-431","doi":"10.1002/jat.4710","pmid":"39435646","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12317","title":"Effects of tryptophan-selective lipidated glucagon-like peptide 1 (GLP-1) peptides on the GLP-1 receptor.","authors":"Lu, Xuejing; Harada, Norio; Yasuda, Takuma; Ikeguchi-Ogura, Eri; Kobayashi, Daishiro; Denda, Masaya; Seno, Yohei; Yamane, Shunsuke; Yabe, Daisuke; Otaka, Akira; Inagaki, Nobuya","year":2025,"journal":"The Journal of endocrinology, 264(3)","doi":"10.1530/JOE-24-0026","pmid":"39807656","tags":[],"studyType":"animal","evidenceStrength":"preliminary","keyFinding":"Two novel GLP-1 peptides created using a simpler manufacturing method — tryptophan-selective lipidation with miniPEG linkers — performed comparably to liraglutide in both cell studies and animal models. Peptide A (one miniPEG linker) matched liraglutide across all measures: cAMP production, insulin secretion, blood glucose lowering, gastrointestinal motility suppression, satiety neuron activation, food intake reduction, and body weight loss. Peptide B (three miniPEG linkers) was equally effective for glucose control but somewhat less potent for appetite suppression.\n\nUnder long-term high-fat diet conditions, both peptides improved glucose tolerance and insulin sensitivity comparably to liraglutide.","whyItMatters":"Manufacturing conventional GLP-1 receptor agonists like semaglutide and liraglutide requires complex chemical processes to attach fatty acid chains that extend their half-life. This study demonstrates that a simpler lipidation method — targeting the peptide's tryptophan residue — can produce equally effective drugs. If this approach scales, it could reduce manufacturing complexity and costs for GLP-1 drugs, potentially improving global access to these increasingly important medications.","specificNumbers":"2 novel peptides tested · Peptide A: 1 miniPEG linker · Peptide B: 3 miniPEG linkers · Both matched liraglutide for glucose lowering · Long-term high-fat diet experiments confirmed sustained efficacy","methodology":"The researchers tested two tryptophan-lipidated GLP-1 peptides in vitro (measuring cAMP production and insulin secretion in cells expressing the GLP-1 receptor) and in vivo in rodent models. Animal experiments assessed blood glucose lowering after oral glucose, gastrointestinal motility, satiety neuron activation in the brain's arcuate nucleus, food intake, body weight, and long-term glucose tolerance and insulin sensitivity under high-fat diet feeding. Liraglutide served as the active comparator throughout.","limitations":"This is a preclinical study using rodent models — results may not translate directly to humans. No pharmacokinetic data (half-life, bioavailability) were reported in the abstract, making it unclear how these peptides would perform with human dosing schedules. The comparison was only to liraglutide, not to newer agents like semaglutide or tirzepatide."},{"rthcId":"RPEP-12318","title":"Efficacy analysis of the Tendvia™ pulmonary artery stent thrombectomy system in the treatment of intermediate- to high-risk pulmonary embolism.","authors":"Lu, Xunlai; Liu, Shengfu; Chen, Changmei; Chen, Junwen; Xu, Shenrui; Luo, Yuanjia; Luo, Jiachao","year":2025,"journal":"Frontiers in cardiovascular medicine, 12, 1685294","doi":"10.3389/fcvm.2025.1685294","pmid":"41163960","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12319","title":"Association of Glucagon-Like Peptide-1 Receptor Agonists With Cancer Risk in Older Adults With Type 2 Diabetes.","authors":"Lu, Ying; Dai, Hao; Tang, Huilin; Donahoo, William T; George, Thomas J; Sun, Ramon C; Jiang, Sizun; Tan, Aik Choon; Guo, Yi; Licht, Jonathan D; Allen, John M; Lee, Kelvin P; Guo, Jingchuan; Bian, Jiang","year":2025,"journal":"Obesity (Silver Spring, Md.)","doi":"10.1002/oby.24366","pmid":"40841345","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In the GLP-1 RA versus SGLT2i matched cohort (21,362 pairs), overall cancer risk was not significantly different (HR 1.03; 95% CI: 0.95-1.12). However, GLP-1 RA users had significantly increased kidney cancer risk (HR 1.43; 95% CI: 1.06-1.92).\n\nIn the GLP-1 RA versus DPP4i matched cohort (20,962 pairs), overall cancer risk was again not different (HR 0.96; 95% CI: 0.89-1.04). However, endometrial cancer risk was significantly elevated (HR 1.55; 95% CI: 1.01-2.37). The nine cancers analyzed were thyroid, pancreatic, bladder, colorectal, lung, kidney, breast, endometrial, and prostate — all considered obesity-associated cancers.","whyItMatters":"With tens of millions of older adults taking GLP-1 drugs, even small increases in specific cancer risks could affect many people. This well-designed Medicare study provides reassurance that overall cancer risk is not elevated, which is important for both patients and prescribers. The kidney and endometrial cancer signals, while requiring confirmation, offer specific targets for enhanced surveillance — a much more useful finding than a vague overall cancer concern.","specificNumbers":"","methodology":"Retrospective cohort study using 2013-2020 national Medicare claims data. Researchers identified cancer-naïve patients with type 2 diabetes who initiated GLP-1 RAs, SGLT2 inhibitors, or DPP4 inhibitors. Propensity score matching (1:1) was used to create balanced comparison groups, adjusting for confounders. Cox proportional hazards models estimated hazard ratios for nine obesity-associated cancers individually and overall.","limitations":"This is a retrospective observational study based on Medicare claims, which may have coding inaccuracies and cannot capture all confounders. The kidney and endometrial cancer signals each came from only one of the two comparisons, raising the possibility of chance findings given multiple comparisons. Medicare patients are older, so findings may not apply to younger GLP-1 drug users. The follow-up period (2013-2020) may not be long enough to capture slow-growing cancers. Specific GLP-1 drug types within the class were not analyzed separately."},{"rthcId":"RPEP-12320","title":"Changes in Cardiovascular Risk Factors and Health Care Expenditures Among Patients Prescribed Semaglutide.","authors":"Lu, Yuan; Liu, Yuntian; Totojani, Tedi; Kim, Chungsoo; Khera, Rohan; Xu, Hua; Brush, John E; Krumholz, Harlan M; Abaluck, Jason","year":2025,"journal":"JAMA network open, 8(8), e2526013","doi":"10.1001/jamanetworkopen.2025.26013","pmid":"40779264","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12321","title":"Exploratory Assessment of Preoperative GLP-1 Receptor Agonists Before Sleeve Gastrectomy: A Retrospective Matched Analysis.","authors":"Luc, Guillaume; Dedieu, Arnaud; Canard, Guillaume; Cesard, Amélie; Brunet, Amandine; Furois, Camille; Leterrier, Angèle; Daridon, Barbara; Mendes, Lea; Brighen, Emilie; Fournet, Lucie; David, Anaelle; Muzard, Ludivine","year":2025,"journal":"Obesity surgery, 35(10), 4383-4392","doi":"10.1007/s11695-025-08258-w","pmid":"40931278","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12322","title":"The Timeline of the Association Between Diabetes and Cardiovascular Diseases: A Narrative Review.","authors":"Luca, Silvia Ana; Bungau, Raluca Malina; Lazar, Sandra; Herascu, Andreea; Gaita, Laura; Avram, Vlad-Florian; Timar, Bogdan","year":2025,"journal":"Journal of clinical medicine, 14(19)","doi":"10.3390/jcm14196877","pmid":"41095961","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12323","title":"Migraine management in France: Practices of general practitioners and neurologists.","authors":"Lucas, C; Raclot, V; Gugenheim, M; Lefebvre, H; Braithwaite, B; Ducros, A","year":2025,"journal":"Revue neurologique, 181(7), 652-666","doi":"10.1016/j.neurol.2025.06.006","pmid":"40681456","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12324","title":"GLP-1 Receptor Agonists in Solid Tumour Therapy: Exploring Their Anticancer Potential and Underlying Molecular Pathways.","authors":"Lucente, Daniela; Bellino, Stefania; La Salvia, Anna","year":2025,"journal":"Genes, 16(11)","doi":"10.3390/genes16111352","pmid":"41300804","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12325","title":"Glucose-Lowering Medications, Glycemia, and Cognitive Outcomes: The GRADE Randomized Clinical Trial.","authors":"Luchsinger, José A; Rosin, Samuel P; Kazemi, Erin J; Younes, Naji; Suratt, Colleen E; Fattaleh, Basma N; Florez, Hermes J; Gonzalez, Jeffrey S; Hollander, Priscilla; Hox, Sophia H; Kuo, Shihchen; Lee, Melissa S; Martens, Thomas; Pop-Busui, Rodica; Seaquist, Elizabeth R; Waltje, Andrea H; Barzilay, Joshua I","year":2025,"journal":"JAMA internal medicine, 185(7), 778-787","doi":"10.1001/jamainternmed.2025.1189","pmid":"40388190","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12326","title":"The impact of type 2 diabetes on aging: multidimensional approaches to preserve cognitive health.","authors":"Lucia, Stefania; Fornaro, Silvia; Federici, Massimo; Rumiati, Raffaella Ida","year":2025,"journal":"Acta diabetologica, 62(12), 2223-2234","doi":"10.1007/s00592-025-02583-3","pmid":"40892247","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12327","title":"Current Insights, Advantages and Challenges of Small Molecule Glucagon-like Peptide 1 Receptor Agonists: A Scoping Review.","authors":"Luna Ceron, Eder; Reddy, Sparsha Duvuru; Kattamuri, Lakshmi; Muvva, Durga Mounika; Chozet, Luis; Bright, Tamis","year":2025,"journal":"Journal of Brown hospital medicine, 4(2), 19-32","doi":"10.56305/001c.132255","pmid":"40191699","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies several key advantages of small molecule GLP-1 receptor agonists over traditional peptide-based versions:\n\n1. Enhanced oral bioavailability without the absorption enhancers needed by oral semaglutide\n2. Better tissue permeability, potentially reaching organs that peptide drugs cannot easily access\n3. Extended half-lives enabling convenient once-daily or potentially less frequent oral dosing\n4. The ability to create fixed-dose combination pills with other diabetes or cardiovascular drugs\n5. Lower manufacturing costs compared to recombinant peptide production\n\nThese advantages could address major barriers to GLP-1 therapy adoption, including needle aversion, adherence challenges, and limited combination therapy options with injectable formulations.","whyItMatters":"The GLP-1 receptor agonist market is one of the fastest-growing in pharmaceutical history, but reliance on injectable peptides limits who can or will use them. Small molecule alternatives could dramatically expand access — no injections, no refrigeration, easy combination with other pills, and potentially lower costs. If these drugs match the efficacy of injectable GLP-1 agonists, they could transform diabetes and obesity treatment from a specialty injection into a simple daily pill.","specificNumbers":"","methodology":"Scoping review of the preclinical and clinical literature on small molecule (non-peptide) GLP-1 receptor agonists. The review examined the pharmacological profiles, preclinical efficacy data, clinical trial progress, and comparative advantages versus peptide-based GLP-1 receptor agonists for type 2 diabetes management.","limitations":"As a scoping review, this paper summarizes existing literature rather than presenting new data. Most small molecule GLP-1 agonists discussed are still in preclinical or early clinical stages, with limited efficacy and safety data compared to the extensive evidence base for injectable peptide GLP-1 drugs. Whether small molecules can match the full therapeutic profile (including cardiovascular and renal benefits) of peptide GLP-1 agonists remains to be demonstrated. Published in a smaller journal, which may limit peer review rigor."},{"rthcId":"RPEP-12328","title":"Long-Term Effect of Semaglutide on the Glomerular Filtration Rate Slope in High-Risk Patients with Diabetic Nephropathy: Analysis in Real-World Clinical Practice.","authors":"Luna, Enrique; Álvarez, Álvaro; Rodriguez-Sabiñón, Jorge; Villa, Juan; Giraldo, Teresa; Martín, Maria Victoria; Vázquez, Eva; Fernández, Noemi; Ruiz, Belén; Garcia-Pino, Guadalupe; Martínez, Coral; Azevedo, Lilia; Diaz, Rosa María; Robles, Nicolas Roberto; Gervasini, Guillermo","year":2025,"journal":"Pharmaceutics, 17(7)","doi":"10.3390/pharmaceutics17070943","pmid":"40733151","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12329","title":"Oral Semaglutide: A Step Forward in Cardiovascular Risk Management for Type 2 Diabetes.","authors":"Luna-Ceron, Eder; Kattamuri, Lakshmi; Duvvuru, Sparsha Reddy; Mukherjee, Debabrata","year":2025,"journal":"Cardiovascular & hematological disorders drug targets, 25(4), 227-230","doi":"10.2174/011871529X421551250801194823","pmid":"40798974","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The SOUL cardiovascular outcome trial demonstrated a 14% reduction in major adverse cardiovascular events (MACE) with oral semaglutide versus placebo in high-risk type 2 diabetes patients. This is the first CVOT to confirm cardiovascular protection with an oral GLP-1 receptor agonist, reinforcing the cardioprotective class effect of GLP-1RAs. The findings suggest improved accessibility for patient populations underrepresented in prior injection-based trials. However, gastrointestinal side effects and strict dosing requirements (taken on an empty stomach with minimal water) challenge long-term adherence.","whyItMatters":"Many patients who could benefit from GLP-1 drugs' cardiovascular protection avoid them because of the injection requirement. An oral formulation that provides the same heart protection could dramatically expand access. The 14% MACE reduction with a pill form means patients can get meaningful cardiovascular risk reduction without needles — a significant advance for medication adherence and health equity, particularly in primary care settings where injectable therapies are less commonly prescribed.","specificNumbers":"","methodology":"Perspective article analyzing the results and implications of the SOUL trial — a randomized, placebo-controlled cardiovascular outcome trial of oral semaglutide in high-risk type 2 diabetes patients. The article contextualizes SOUL within the broader landscape of GLP-1RA cardiovascular outcome trials.","limitations":"This is a perspective article, not the primary trial publication, so detailed trial data and methodology are not presented. The 14% MACE reduction with oral semaglutide has not been directly compared to injectable semaglutide's cardiovascular benefits. Gastrointestinal side effects may limit real-world adherence more than in the controlled trial setting. The strict dosing requirements (fasting, 30+ minutes before food) may be challenging for many patients. Cost-effectiveness and long-term adherence data are still needed."},{"rthcId":"RPEP-12330","title":"Gastrointestinal hormones and subjective ratings of appetite after low-carbohydrate vs low-fat low-energy diets in females with lipedema - A randomized controlled trial.","authors":"Lundanes, Julianne; Storliløkken, Gunnhild Eggen; Solem, Marte Siwsdotter; Dankel, Simon N; Tangvik, Randi J; Ødegård, Rønnaug; Holst, Jens Juul; Rehfeld, Jens Frederik; Martins, Catia; Nymo, Siren","year":2025,"journal":"Clinical nutrition ESPEN, 65, 16-24","doi":"10.1016/j.clnesp.2024.11.018","pmid":"39566600","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12331","title":"Administration of a Next-Generation Probiotic Escherichia coli Nissle 1917-GLP-1 Alleviates Diabetes in Mice With Type 1 and Type 2 Diabetes.","authors":"Luo, Jie; Fang, Yilin; Qi, Zhanghua; Cui, Fengyang; Hu, Hong; Li, Shengjie; Chen, Tingtao; Zhang, Hongyan","year":2025,"journal":"The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale, 2025, 6675676","doi":"10.1155/cjid/6675676","pmid":"39949529","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12332","title":"Comprehensive understanding of a rare disease: Cardiac metastatic tumor, a double-center 10-year case review.","authors":"Luo, Ling-Yun; Yang, Tian-Shu; He, Zhen; Lin, Li; Luo, Xue-Lian","year":2025,"journal":"World journal of cardiology, 17(2), 101851","doi":"10.4330/wjc.v17.i2.101851","pmid":"40061273","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12333","title":"Bifidobacterium Lactobacillus Triple Viable Alleviates Slow Transit Constipation by Regulating Gut Microbiota and Metabolism.","authors":"Luo, Mei; Xie, Peiwei; Deng, Xuehong; Fan, Jiahui; Xiong, Lishou","year":2025,"journal":"Journal of gastroenterology and hepatology, 40(6), 1561-1573","doi":"10.1111/jgh.16960","pmid":"40183209","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12334","title":"A novel dual CCK/ GLP-1 receptor agonist ameliorates cognitive impairment in 5 × FAD mice by modulating mitophagy via the PINK1/Parkin pathway.","authors":"Luo, Rihong; Kang, Yuhan; Ma, He; Zhang, Zhenqiang; Hölscher, Christian; Hao, Li; Zhang, Zijuan","year":2025,"journal":"International immunopharmacology, 154, 114612","doi":"10.1016/j.intimp.2025.114612","pmid":"40184808","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The novel dual CCK/GLP-1 receptor agonist demonstrated multiple neuroprotective effects in 5×FAD Alzheimer's mice:\n\n- Improved cognitive deficits (memory and learning)\n- Reduced amyloid-beta (Aβ) accumulation in the brain\n- Alleviated mitochondrial damage through induction of mitophagy\n- Regulated PINK1/Parkin-mediated mitophagy pathway (confirmed in both in vivo and Aβ-treated cell models)\n- Outperformed the GLP-1 analogue liraglutide on certain indicators\n\nThis is the first demonstration that a CCK/GLP-1 dual agonist modulates mitophagy via the PINK1/Parkin pathway to enhance cognitive function in an Alzheimer's model.","whyItMatters":"Alzheimer's disease remains one of the greatest unmet medical needs, affecting over 55 million people worldwide. GLP-1 drugs have generated excitement as potential Alzheimer's treatments (semaglutide is currently in clinical trials), but this study suggests that combining GLP-1 with CCK receptor activation may be even more effective. The dual approach targets brain inflammation, amyloid clearance, and mitochondrial health simultaneously — addressing multiple Alzheimer's pathways through a single peptide drug.","specificNumbers":"","methodology":"Researchers tested a novel dual CCK/GLP-1 receptor agonist in 5×FAD transgenic mice (a model carrying five familial Alzheimer's mutations that develops aggressive amyloid pathology). Cognitive performance was assessed using behavioral testing. Brain amyloid-beta levels, mitochondrial integrity, and mitophagy markers were measured. The PINK1/Parkin mitophagy pathway was investigated in vivo and confirmed in an in vitro Aβ-induced cell model. Results were compared against liraglutide (a standard GLP-1 RA) and vehicle control groups.","limitations":"The 5×FAD mouse model represents aggressive familial Alzheimer's with rapid amyloid accumulation, which differs from the slower, more complex human sporadic Alzheimer's. The comparison with liraglutide is incomplete — 'certain indicators' were superior but the abstract doesn't specify which outcomes or by how much. The novel dual agonist has not been tested in humans, and brain penetration, pharmacokinetics, and safety in humans are unknown. The study does not address tau pathology, another key Alzheimer's feature. Specific cognitive test results and quantitative measurements are not detailed in the abstract."},{"rthcId":"RPEP-12335","title":"Inhibition of Tumor Lipogenesis and Growth by Peptide-Based Targeting of SREBP Activation.","authors":"Luo, Shudi; Yang, Huang; Jiang, Xiaoming; Wang, Zheng; He, Xuxiao; Meng, Ying; Li, Shan; Li, Min; Xu, Daqian; Mao, Zhengwei; Lu, Zhimin","year":2025,"journal":"Advanced science (Weinheim, Baden-Wurttemberg, Germany), 12(45), e08111","doi":"10.1002/advs.202508111","pmid":"40959854","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A peptide mimicking the Insig1/2 loop 1 region blocked the interaction between PCK1 and Insig1/2, shutting down the SREBP1 pathway that cancer cells use to produce the lipids they need to grow. When delivered intravenously in liposomal nanoparticles, the peptide suppressed tumor growth and extended survival in mice without apparent side effects. Combining the peptide with either lenvatinib (a cancer drug) or semaglutide (an anti-obesity drug) produced additive anti-tumor effects. This is the first demonstration that SREBP — previously considered 'untargetable' — can be inhibited with a peptide therapeutic.","whyItMatters":"Cancer cells produce far more fat molecules than normal cells, fueling their rapid growth. The SREBP pathway controlling this fat production has been considered a promising but 'undruggable' cancer target. This study shows a peptide can hit it effectively, opening a new class of cancer therapy. The finding that semaglutide (a GLP-1 weight loss drug) has additive anti-tumor effects when combined with the peptide is particularly striking, connecting obesity treatment and cancer therapy.","specificNumbers":"","methodology":"The researchers designed a peptide replicating the amino acid sequence of the Insig1/2 loop 1 region and tested it in tumor cell lines to measure effects on SREBP1 nuclear accumulation, lipid gene expression, lipid accumulation, and cell proliferation. For in vivo testing, they encapsulated the peptide in engineered liposomal nanoparticles (LNPs) and administered them intravenously to tumor-bearing mice, measuring tumor growth and survival. Combination experiments tested the peptide with lenvatinib and semaglutide.","limitations":"This is a preclinical study in cell lines and mouse models — human safety and efficacy are unknown. The LNP delivery system, while effective in mice, would need significant optimization for human use. Long-term effects of blocking SREBP-mediated lipogenesis on normal cells that also require fat synthesis are not addressed. The mechanisms behind semaglutide's additive effect were not fully explored."},{"rthcId":"RPEP-12336","title":"AaeAP2a, a scorpion-derived antimicrobial peptide, combats carbapenem-resistant Acinetobacter baumannii via membrane disruption and triggered metabolic collapse.","authors":"Luo, Weiyu; Zhang, Liuwei; Gao, Haolei; Li, Huiying; Li, Xiaofeng; Wen, Yuliang; Sun, Huarun; Hang, Bolin; Zhang, Longfei; Zhang, Wei; Liu, Xuehan; Wang, Ruibiao; Wen, Bo; Shen, Jiyuan; Zhu, Chunling; Bai, Yueyu; Wang, Lei; Ding, Ke; Hu, Jianhe","year":2025,"journal":"Frontiers in microbiology, 16, 1673333","doi":"10.3389/fmicb.2025.1673333","pmid":"41229684","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12337","title":"Design and function analysis of novel antimicrobial peptides derived from Cathelicidin-DM: Insights into structure-function relationships.","authors":"Luo, Ying; Dong, Zhan; Shi, Yaoqiang; Wang, Lei; Chen, Zhizhi; Yan, Shuo; Wang, Guanlin; Han, Qinqin; Zhang, Jinyang; Li, Chao; Song, Yuzhu","year":2025,"journal":"European journal of medicinal chemistry, 300, 118173","doi":"10.1016/j.ejmech.2025.118173","pmid":"40961583","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Over 20 AMPs derived from Cathelicidin-DM were designed with variations in sequence size, amino acid composition, amphiphilicity, and amidation. Key finding: hydrophobic amino acid substitution was the most significant factor for improving biological activity. Lead candidates demonstrated antimicrobial activity both in vitro and in vivo, anti-inflammatory properties, acceptable safety profiles, and structural stability. Structure-function analysis clarified the relationships between peptide design parameters and functional outcomes.","whyItMatters":"Developing AMPs into drugs requires understanding which structural features drive activity, safety, and stability — and which can be sacrificed. This systematic approach provides a roadmap for peptide engineers: by showing that hydrophobicity is the key tunable parameter, it focuses future design efforts. The demonstration of both antimicrobial and anti-inflammatory activity in vivo moves these peptides closer to clinical candidacy.","specificNumbers":"","methodology":"Systematic peptide design study creating 20+ variants of Cathelicidin-DM with controlled modifications. Each variant was evaluated for: in vitro antimicrobial activity (MIC testing), in vivo antimicrobial efficacy (animal infection models), peptide structure (biophysical characterization), safety assessment (hemolysis and cell toxicity), stability testing, antimicrobial mechanism of action, anti-inflammatory activity, and in vivo toxicity.","limitations":"The study focuses on one AMP family (Cathelicidin-DM derivatives), and findings may not generalize to all AMP classes. Over 20 variants were tested, but the design space for peptide modifications is enormous — important variables may have been missed. The abstract doesn't provide specific MIC values or quantitative comparisons between variants. In vivo efficacy and toxicity models are described but without detailed outcomes. Manufacturing cost and scalability of the optimized peptides were not addressed."},{"rthcId":"RPEP-12338","title":"GLP-1 signaling in tumor metabolism and immunity: mechanisms and strategies.","authors":"Luo, Yingzhe; Xu, Huimin; Zhao, Yaqin; Yang, Biao; Zhang, Ying","year":2025,"journal":"Food & function, 16(23), 8943-8964","doi":"10.1039/d5fo03273c","pmid":"41160511","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12339","title":"Both subcutaneous semaglutide and calorie restriction improves pancreatic cell hyperplasia and gut microbiota in high-fat diet-induced obese mice.","authors":"Luo, Yunfei; Yang, Shiqi; Zeng, Haixia; Liu, Shuang; Zhang, Yuying; Li, Jin-E; Liu, Jianping","year":2025,"journal":"Nutrition & metabolism, 22(1), 95","doi":"10.1186/s12986-025-00987-0","pmid":"40775354","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12340","title":"Semaglutide alleviates the pancreatic β cell function via the METTL14 signaling and modulating gut microbiota in type 2 diabetes mellitus mice.","authors":"Luo, Yunfei; Li, Jin-E; Zeng, Haixia; Zhang, Yuying; Yang, Shiqi; Liu, Jianping","year":2025,"journal":"Life sciences, 361, 123328","doi":"10.1016/j.lfs.2024.123328","pmid":"39719165","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide treatment (40 μg/kg for 4 weeks) in diabetic mice reversed pancreatic damage, enhanced islet cell proliferation, and restored both alpha- and beta-cell masses to near-normal levels. At the molecular level, semaglutide upregulated the m6A methyltransferase METTL14, which regulated PDX-1 expression in an m6A-dependent manner — a previously unknown mechanism for semaglutide's beta cell protection.\n\nThe drug also significantly altered gut microbiota composition, decreasing Firmicutes, Actinobacteriota, and Lactobacillus abundance while increasing Bacteroides and norank_f_Muribaculaceae. Short-chain fatty acid production was also boosted, suggesting a gut-pancreas signaling axis.","whyItMatters":"Most people know semaglutide as a weight loss and blood sugar drug, but this study reveals it may also protect the insulin-producing cells themselves through a newly identified RNA modification pathway. If these molecular mechanisms translate to humans, it could mean semaglutide does more than manage diabetes symptoms — it might help preserve the beta cells that diabetes gradually destroys.","specificNumbers":"","methodology":"Researchers used five-week-old male C57BL/6 mice, splitting them into control and high-fat diet groups. After four weeks on a high-fat diet, type 2 diabetes was induced using streptozotocin injections. Diabetic mice then received either no treatment or semaglutide (40 μg/kg) for another four weeks. The team examined pancreatic tissue using immunofluorescence, measured protein levels with Western blot, and assessed gene expression with RT-qPCR. They also studied the mechanism in palmitic acid-stressed beta-TC-6 cells in the lab and analyzed gut bacteria composition.","limitations":"This was an animal study using mice, so results may not directly apply to humans. The diabetes model used streptozotocin, which causes more severe beta cell damage than typical human type 2 diabetes. The study period was only four weeks, too short to assess long-term beta cell preservation. The specific contribution of gut microbiome changes versus direct METTL14 effects was not fully disentangled."},{"rthcId":"RPEP-12341","title":"Ocular adverse events associated with GLP-1 receptor agonists: a real-world study based on the FAERS database and network pharmacology.","authors":"Luo, Zhan-Yang; Li, Xiang; Chen, Cui-Ting; Kang, Hong-Hua; Zhang, Zhi-Jie; Wang, Dong; Gong, Jing-Ru","year":2025,"journal":"Expert opinion on drug safety, 24(3), 287-296","doi":"10.1080/14740338.2024.2419989","pmid":"39425661","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12342","title":"Reduced serum levels of mitochondria-derived peptide MOTS-c in patients with obstructive sleep apnea.","authors":"Luo, Zhuoding; Ji, Rui; Ye, Renjing; Shi, Yawen; Pang, Qingfeng; Yin, Min","year":2025,"journal":"Sleep and biological rhythms, 23(3), 305-311","doi":"10.1007/s41105-025-00578-9","pmid":"40538389","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 77 participants (53 OSA patients, 24 controls), serum MOTS-c levels were significantly correlated with BMI, AHI (Apnea-Hypopnea Index), and ODI (Oxygen Desaturation Index) independent of age. MOTS-c levels decreased progressively with OSA severity: patients with severe OSA had lower levels than those with moderate OSA, who had lower levels than those with mild OSA.\n\nCritically, ANCOVA analysis with BMI as a covariate demonstrated that OSA severity was an independent factor influencing serum MOTS-c levels — meaning the relationship isn't simply explained by obesity. This suggests a direct biological connection between the intermittent oxygen deprivation in OSA and mitochondrial peptide production.","whyItMatters":"Sleep apnea affects an estimated 1 billion people worldwide and is linked to metabolic problems, cardiovascular disease, and diabetes. Understanding why metabolic dysfunction occurs in OSA could lead to new treatments. MOTS-c, as an exercise-mimicking mitochondrial peptide, could represent both a biomarker for OSA severity and a potential therapeutic target — supplementing MOTS-c might help counteract the metabolic damage caused by repeated oxygen drops during sleep.","specificNumbers":"","methodology":"This cross-sectional study enrolled 77 participants: 8 with mild OSA, 16 with moderate OSA, 29 with severe OSA, and 24 controls. Serum MOTS-c levels were measured by immunoassay. All participants underwent polysomnography (sleep study) and had complete blood counts, demographic data, and sleep questionnaires collected. Statistical analysis included correlation, ANOVA, and ANCOVA with BMI as covariate.","limitations":"This is a cross-sectional observational study that cannot establish causation — it's unclear whether low MOTS-c causes OSA-related metabolic problems or is a consequence of them. The sample size of 77 is relatively small, particularly for subgroup analysis by OSA severity. MOTS-c measurement was from a single time point and may not reflect dynamic changes. The study did not assess whether CPAP treatment restores MOTS-c levels. Potential confounders like physical activity level and diet were not controlled."},{"rthcId":"RPEP-12343","title":"Capture of fusion-intermediate conformations of SARS-CoV-2 spike requires receptor binding and cleavage at either the S1/S2 or S2' site.","authors":"Lusvarghi, Sabrina; Vassell, Russell; Williams, Brittany; Baha, Haseebullah; Neerukonda, Sabari Nath; Weiss, Carol D","year":2025,"journal":"PLoS pathogens, 21(4), e1012808","doi":"10.1371/journal.ppat.1012808","pmid":"40198676","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12344","title":"Role of amylin in feeding and satiation.","authors":"Lutz, Thomas A","year":2025,"journal":"Neuropharmacology, 278, 110587","doi":"10.1016/j.neuropharm.2025.110587","pmid":"40639451","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Amylin's primary eating-related effect is rapid, short-lasting satiation that controls meal size, directly reflecting meal-induced rises in circulating amylin. This effect is mediated by humoral (blood-borne) action in the central nervous system, with the area postrema in the caudal hindbrain being the key target region. Amylin also reduces food reward, specifically reducing high-fat food intake in certain conditions. In humans, amylin receptor agonists have reduced binge eating episodes. Long-acting amylin receptor agonists combined with GLP-1 receptor agonists (particularly semaglutide) have emerged as highly promising obesity therapeutics.","whyItMatters":"The combination of amylin and GLP-1 agonists (like cagrilintide plus semaglutide, marketed as CagriSema) is one of the most anticipated obesity drug combinations in development. Understanding how amylin controls eating through different mechanisms than GLP-1 helps explain why combining them produces greater weight loss than either alone.","specificNumbers":"","methodology":"This is a narrative review summarizing the key literature on amylin's effects on eating behavior, including its mechanisms of action, brain targets, effects on food reward and binge eating, and the therapeutic potential of long-acting amylin receptor agonists alone and in combination therapy.","limitations":"As a review, this paper does not present new data. Much of the foundational research on amylin's eating effects comes from animal models. The review focuses primarily on satiation and food reward effects, not addressing amylin's other metabolic roles. Specific clinical trial results for newer amylin agonists and combination therapies are referenced but not detailed."},{"rthcId":"RPEP-12345","title":"Newer Glucagon-Like Peptide-1 Receptor Agonists Are Associated With Improved Glycemic Control in US Adults With Type 2 Diabetes: A Population-Level Time Series Analysis.","authors":"Lv, Lei; Wang, Yan; Xie, Lin; Noone, Josh; Alvarez, Sara; Zhang, Yuehan; Song, Yan; Rotroff, Daniel M","year":2025,"journal":"Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research, 28(5), 712-719","doi":"10.1016/j.jval.2025.01.018","pmid":"39947393","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12346","title":"Analgesia using sufentanil and sufentanil plus dexmedetomidine following cesarean section and effect on placental hypoxia-inducible factors.","authors":"Lv, Xiaoling; Lin, Xiaoping; Ma, Long","year":2025,"journal":"International journal of clinical pharmacology and therapeutics, 63(12), 601-608","doi":"10.5414/CP204733","pmid":"40964781","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12347","title":"Glucagon-like Peptide-1 Receptor (GLP-1R) Signaling: Making the Case for a Functionally Gs Protein-Selective GPCR.","authors":"Lymperopoulos, Anastasios; Altsman, Victoria L; Stoicovy, Renee A","year":2025,"journal":"International journal of molecular sciences, 26(15)","doi":"10.3390/ijms26157239","pmid":"40806371","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The GLP-1 receptor (GLP-1R) does not undergo significant desensitization in physiologically relevant tissues in vivo, instead producing robust and prolonged cAMP signals through Gs protein coupling. This contrasts sharply with the GIP receptor (GIPR), which extensively uses βarrestin signaling and undergoes significant desensitization, internalization, and downregulation.\n\nThe GLP-1R's resistance to desensitization may be explained by its unique property of constantly cycling between the cell membrane and caveolae/lipid rafts. The review argues this makes GLP-1R a functionally Gs-selective receptor — a distinction with major implications for designing next-generation multi-receptor agonist drugs (poly-ligands) targeting obesity.","whyItMatters":"Understanding why the GLP-1 receptor produces such sustained signaling is critical for designing better obesity drugs. The current wave of multi-receptor agonists (tirzepatide targets GLP-1R + GIPR; retatrutide targets three receptors) needs to account for the very different signaling behaviors of each receptor. If GLP-1R is truly Gs-selective and desensitization-resistant while GIPR is βarrestin-heavy and rapidly desensitizing, this fundamentally changes how combination drugs should be engineered.","specificNumbers":"","methodology":"This is a review article synthesizing experimental evidence from receptor pharmacology, cell signaling studies, and in vivo experiments regarding GLP-1R and GIPR signaling properties, desensitization behavior, and ligand bias.","limitations":"This is a review/perspective article making a theoretical case for GLP-1R Gs-selectivity. While supported by substantial evidence, the hypothesis that caveolae cycling prevents desensitization needs further direct confirmation. The clinical implications for poly-ligand drug design are logical extrapolations, not proven outcomes."},{"rthcId":"RPEP-12348","title":"Calcitonin Gene-Related Peptide (CGRP)-Expressing Neurons in the External Lateral Parabrachial Area Regulate Pain-Induced Sleep Disturbances.","authors":"Lynch, Nicole; De Luca, Roberto; Spinieli, Richard L; Rillosi, Enrico; Thomas, Renner C; Sailesh, Samuel; Gangeddula, Nishta; Lima, Janayna D; Bandaru, Sathyajit S; Arrigoni, Elda; Melo-Carrillo, Agustin; Burstein, Rami; Thankachan, Stephen; Kaur, Satvinder","year":2025,"journal":"Advanced science (Weinheim, Baden-Wurttemberg, Germany), 12(35), e00325","doi":"10.1002/advs.202500325","pmid":"40583282","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12349","title":"Oxytocin improves maternal licking behavior deficits in autism-associated Shank3 mutant dogs.","authors":"Lyu, Wen; Li, Yuan; Yao, Aiyu; Tan, Qing-Quan; Zhang, Rong; Zhao, Jian-Ping; Guo, Kun; Jiang, Yong-Hui; Tian, Rui; Zhang, Yong Q","year":2025,"journal":"Translational psychiatry, 15(1), 76","doi":"10.1038/s41398-025-03296-5","pmid":"40050270","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Shank3 mutant mother dogs exhibited significantly fewer and shorter licking bouts and reduced nursing frequency compared to wild-type dams. Blood oxytocin concentrations were significantly decreased in mutant dams. A two-week vehicle-controlled intranasal oxytocin treatment, starting on postpartum day 8, significantly rescued the licking behavior deficits both acutely and chronically. This demonstrates that the maternal behavior impairments in these autism-model dogs are at least partly driven by oxytocin system dysfunction.","whyItMatters":"Most autism research uses mice, but dogs are far more socially complex and may better model human social behavior deficits. This study validates Shank3-mutant dogs as a new large-animal autism model and provides compelling evidence that oxytocin can rescue specific social behavior deficits caused by this genetic mutation. The finding that both acute and chronic oxytocin treatment worked is particularly encouraging for therapeutic development, as it suggests sustained benefit rather than just a temporary effect.","specificNumbers":"","methodology":"Researchers generated Shank3 mutant domestic dogs using CRISPR/Cas9 gene editing. Maternal behaviors (licking frequency, licking duration, nursing frequency) were quantified in mutant and wild-type dams with their puppies. Blood oxytocin levels were measured. A vehicle-controlled experiment tested two weeks of intranasal oxytocin treatment beginning on postpartum day 8, with both acute and chronic behavioral assessments.","limitations":"The abstract does not specify the number of dogs in each group, making it difficult to assess statistical power. Dogs, while more socially complex than mice, are still not humans, and maternal licking is only one facet of social behavior. The two-week treatment window is short, and long-term effects are unknown. The study focused on a single gene (SHANK3), which accounts for only a subset of autism cases. Intranasal oxytocin delivery to the brain is not fully understood even in humans."},{"rthcId":"RPEP-12350","title":"Peptide dendrimers: Novel therapeutic opportunities for peptide-based biomaterials in biomedicine.","authors":"Lyu, Yinfeng; Xue, Meng; Huang, Xinyue; Bian, Yifeng; Li, Peiyang; Yang, Chengyi; Zhang, Licong; Shan, Anshan","year":2025,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 388(Pt 1), 114322","doi":"10.1016/j.jconrel.2025.114322","pmid":"41101696","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12351","title":"A Novel Presentation of Euglycemic Diabetic Ketoacidosis Associated with SGLT2 Inhibitor and Weekly GLP-1 Agonist: Case Report.","authors":"Lyu, Young Sang","year":2025,"journal":"Healthcare (Basel, Switzerland), 13(17)","doi":"10.3390/healthcare13172245","pmid":"40941597","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12352","title":"Repurposing Semaglutide and Liraglutide for Alcohol Use Disorder.","authors":"Lähteenvuo, Markku; Tiihonen, Jari; Solismaa, Anssi; Tanskanen, Antti; Mittendorfer-Rutz, Ellenor; Taipale, Heidi","year":2025,"journal":"JAMA psychiatry, 82(1), 94-98","doi":"10.1001/jamapsychiatry.2024.3599","pmid":"39535805","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 227,866 individuals with AUD (63.5% male, mean age 40, median follow-up 8.8 years), within-individual comparisons showed:\n\n- Semaglutide (4,321 users): 36% reduced AUD hospitalization risk (aHR 0.64, 95% CI: 0.50-0.83), 32% reduced any SUD hospitalization (aHR 0.68, 95% CI: 0.54-0.85), 22% reduced somatic hospitalization (aHR 0.78, 95% CI: 0.68-0.90)\n- Liraglutide (2,509 users): 28% reduced AUD hospitalization risk (aHR 0.72, 95% CI: 0.57-0.92), 22% reduced any SUD hospitalization (aHR 0.78, 95% CI: 0.64-0.97), 21% reduced somatic hospitalization (aHR 0.79, 95% CI: 0.69-0.91)\n- Approved AUD medications: Only 2% reduced AUD hospitalization (aHR 0.98, 95% CI: 0.96-1.00)\n- Neither drug was significantly associated with suicide attempt risk","whyItMatters":"Alcohol use disorder is a leading cause of preventable death, and current approved medications (naltrexone, acamprosate, disulfiram) have limited effectiveness and are underused. If GLP-1 drugs can substantially reduce alcohol-related harm — as this study suggests — it would represent a transformative addition to AUD treatment. The effect sizes seen here (36% reduction with semaglutide) far exceed those of approved AUD medications in this same population. Published in JAMA Psychiatry, this is among the strongest real-world evidence to date for GLP-1 drugs in addiction.","specificNumbers":"","methodology":"This was a nationwide Swedish register-based observational cohort study spanning January 2006 to December 2023. The population included all residents aged 16-64 with an AUD diagnosis, identified from inpatient, outpatient, sickness absence, and disability pension registers. The primary analysis used a Cox regression within-individual model, which compares each person's outcomes during periods of GLP-1 agonist use versus non-use — eliminating all time-invariant confounders (genetics, demographics, baseline health). Primary outcome was AUD hospitalization; secondary outcomes included any SUD hospitalization, somatic hospitalization, and suicide attempts.","limitations":"This is an observational study — despite the strong within-individual design, it cannot definitively prove causation. GLP-1 drug users had comorbid obesity/diabetes, and periods of GLP-1 use may coincide with periods of better overall health engagement (healthy user bias). The number of GLP-1 users (4,321 semaglutide, 2,509 liraglutide) is a fraction of the total AUD cohort. The study cannot determine whether GLP-1 drugs directly reduce alcohol craving/consumption or indirectly improve outcomes through weight loss, better diabetes control, or overall health improvement. Results may not generalize to AUD patients without metabolic comorbidities."},{"rthcId":"RPEP-12353","title":"Genome Mining and Structural Study of Cathelicidins Across Chiroptera Species.","authors":"López, Manuel R; González-Almécija, Beatriz; Farrais-Solana, Francisco; Otazo-Pérez, Andrea; González-Acosta, Sergio; Asensio-Calavia, Patricia; Morales-delaNuez, Antonio; Pérez de la Lastra, José-Manuel","year":2025,"journal":"Biochemistry research international, 2025, 5461549","doi":"10.1155/bri/5461549","pmid":"41036148","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12354","title":"Patient satisfaction with calcitonin gene-related peptide monoclonal antibodies in migraine: A multicenter prospective cohort study.","authors":"López-Bravo, Alba; Mínguez-Olaondo, Ane; Nieves-Castellanos, Candela; Ruibal-Salgado, Marta; Sánchez-Mateos, Noemí Morollón; Navarro-Pérez, María Pilar; Alpuente, Alicia; Torres-Ferrús, Marta; García-Ull, Jésica; Gago-Veiga, Ana; García-Azorín, David; González-Martínez, Alicia; Sierra, Álvaro; Santos-Lasaosa, Sonia","year":2025,"journal":"Headache, 65(6), 994-1004","doi":"10.1111/head.14913","pmid":"40135519","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12355","title":"Low-Molecular-Weight Bovine Collagen Peptides Reduce Fat Accumulation in C. elegans and Ameliorate Obesity-Related Metabolic Dysfunction and Microbiota Diversity in C57BL/6 Male Diet-Induced Obese Mice.","authors":"López-Yoldi, Miguel; Aranaz, Paula; Riezu-Boj, José I; González-Salazar, Itxaso; Izco, Jesús M; Recalde, José I; González-Navarro, Carlos J; Milagro, Fermín I","year":2025,"journal":"International journal of molecular sciences, 26(18)","doi":"10.3390/ijms26189149","pmid":"41009711","tags":["collagen-peptides","obesity","microbiome","metabolic-syndrome"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"In C. elegans, low-molecular-weight bovine collagen hydrolysate (2 mg/mL) significantly reduced fat accumulation and reactive oxygen species, slowed aging (measured by lipofuscin), and extended median lifespan.\n\nIn 32 male diet-induced obese C57BL/6 mice, 8 weeks of daily supplementation (1 mg/animal/day) produced significant reductions in adipose tissue: mesenteric fat decreased 28%, visceral fat decreased 15%, and total adipose tissue decreased 18%. Glucose tolerance improved markedly, with a 26% reduction in area under the curve on glucose tolerance testing (p < 0.05). The collagen peptides also significantly increased gut microbiota diversity and shifted bacterial populations toward beneficial species.","whyItMatters":"Collagen peptide supplements are already widely consumed for skin and joint health, making them accessible and generally well-tolerated. If they also provide meaningful metabolic benefits — reducing visceral fat, improving blood sugar control, and supporting gut health — it would add significant value to an already popular supplement category. The gut microbiome changes are particularly interesting because they suggest a mechanism by which collagen peptides might influence metabolism systemically.","specificNumbers":"Mesenteric fat ↓28%, visceral fat ↓15%, total fat ↓18% (p>0.05); glucose tolerance ↑26% AUC (p<0.05); 32 mice; 8 weeks; 1 mg/day; C. elegans: 2 mg/mL","methodology":"Researchers tested low-molecular-weight bovine collagen hydrolysate (COLLinstant® LMW) in two model organisms. In C. elegans worms, they measured fat accumulation (Nile Red staining), reactive oxygen species (dihydroethidium), aging markers (lipofuscin), and lifespan. In 32 male diet-induced obese C57BL/6 mice, they supplemented daily for 8 weeks and measured adipose tissue depots, glucose tolerance (intraperitoneal glucose tolerance test), and gut microbiota composition and diversity.","limitations":"The fat tissue reductions (28%, 15%, 18%) were noted to have p > 0.05, meaning they did not reach statistical significance — only the glucose tolerance improvement was significant (p < 0.05). The mouse dose (1 mg/day) may not translate proportionally to a human dose. The study used a specific commercial product (COLLinstant® LMW), so results may not apply to all collagen supplements. Only male mice were studied. The 8-week duration is relatively short. The C. elegans model, while useful for screening, has limited relevance to human metabolism."},{"rthcId":"RPEP-12356","title":"Baseline characteristics and 1-year outcome by left ventricular function in the CABG PREFERS.","authors":"Löfström, Ulrika; Linde, Cecilia; Eriksson, Maria J; Maret, Eva; Corbascio, Matthias; Ekström, Mattias; Lyngå, Patrik; Wallén, Håkan; Persson, Bengt; Persson, Hans; Hage, Camilla","year":2025,"journal":"European heart journal open, 5(2), oeaf014","doi":"10.1093/ehjopen/oeaf014","pmid":"40177505","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12357","title":"The Composite Number Needed to Treat for Semaglutide in Populations with Overweight or Obesity and Established Cardiovascular Disease Without Diabetes.","authors":"Lübker, Christopher; Bhavsar, Jigish; Duque do Vale, Ruben; Emerson, Scott S; Nørtoft, Emil; Plutzky, Jorge; Roberts, Geraint; Tarp, Jens Magelund; Lincoff, A Michael","year":2025,"journal":"Advances in therapy, 42(5), 2513-2525","doi":"10.1007/s12325-025-03176-w","pmid":"40156748","tags":["glp-1-agonists","cardiovascular"],"studyType":"secondary-analysis","evidenceStrength":"strong","keyFinding":"When semaglutide's benefits are measured only by its primary endpoint of major adverse cardiovascular events (MACE), 58 patients need treatment for 4 years to prevent one event (NNT=58). But when the analysis includes hospitalizations, coronary revascularization, non-cardiovascular death, new diabetes onset, and kidney outcomes, only 11 patients need treatment for 4 years to prevent one adverse outcome (NNT=11).\n\nThe composite risk reductions were 20% for MACE alone, 20% for the extended composite, and 41% when cardiorenal-metabolic outcomes were included. At just 1 year, the broadest composite NNT was already 20, meaning one patient benefits for every 20 treated.","whyItMatters":"Number needed to treat (NNT) is how payers, insurers, and health systems decide whether a drug is worth its cost. Semaglutide's headline NNT of 58 for MACE alone might not impress decision-makers, but when its broader benefits — fewer hospitalizations, less kidney disease, prevention of new diabetes — are included, the NNT drops to just 11. This analysis makes a powerful economic and clinical case that semaglutide delivers far more value than its primary trial endpoint suggests, which could influence insurance coverage and prescribing decisions for millions of patients.","specificNumbers":"n=17,604 · 39.8 months mean follow-up · MACE risk reduction: 20% · cardiorenal-metabolic risk reduction: 41% · NNT at 4 years: 58 (MACE), 25 (extended), 11 (broadest) · NNT at 1 year: 125 (MACE), 49 (extended), 20 (broadest)","methodology":"Secondary analysis of the SELECT trial, a randomized, double-blind, placebo-controlled phase III cardiovascular outcomes trial. 17,604 patients with overweight/obesity and established cardiovascular disease (without diabetes) received once-weekly subcutaneous semaglutide or placebo for a mean of 39.8 months. NNTs were calculated for three progressively broader composites: 3-point MACE (CV death, non-fatal MI, non-fatal stroke), an extended composite adding hospitalizations, revascularization, and non-CV death, and a cardiorenal-metabolic composite adding HbA1c ≥6.5% and a nephropathy composite.","limitations":"This is a secondary analysis, not the primary SELECT trial itself. The broadest composite (NNTCKM) includes outcomes of varying clinical severity, so a prevented case of new-onset diabetes is counted equally with a prevented heart attack. The SELECT trial excluded patients with diabetes, so these NNTs apply only to the overweight/obese cardiovascular disease population without diabetes. Combining multiple endpoints improves NNT by definition, so the improvement partly reflects methodology rather than additional drug efficacy."},{"rthcId":"RPEP-12358","title":"Metabolism of new drug modalities research advances - 2024 year in review.","authors":"Ma, Bin; Argikar, Upendra A; Chen, Luying; Cheruzel, Lionel; Cho, Sungjoon; Gu, Ting-Jia; Hauri, Simon; Kramlinger, Valerie M; Li, Xiuli; Liu, Joyce; Schadt, Simone; Seneviratne, Herana Kamal; Shi, Rachel Liuqing; Tang, Lloyd Wei Tat; Zhang, Donglu; Zhong, Guo; Khojasteh, S Cyrus","year":2025,"journal":"Drug metabolism reviews, 57(4), 467-504","doi":"10.1080/03602532.2025.2542220","pmid":"40757795","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12359","title":"Overcoming Challenges in the Metabolism of Peptide Therapeutics: Strategies and Case Studies for Clinical Success.","authors":"Ma, Bin; Fuhrmann, Jakob; Henriksen, Hanne; Khojasteh, S Cyrus; Li, Wanqing; Liu, Joyce; Plise, Emile; Yu, Qinying; Cheruzel, Lionel","year":2025,"journal":"Journal of medicinal chemistry, 68(24), 25689-25707","doi":"10.1021/acs.jmedchem.5c02276","pmid":"41348552","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12360","title":"A novel Dual GLP-1/CCK Receptor Agonist Improves Cognitive Performance and Synaptogenesis in the 5 × FAD Alzheimer Mouse Model.","authors":"Ma, He; Chang, Zhenghui; Sun, Hongyu; Ma, Dongrui; Li, Zhonghua; Hao, Li; Zhang, Zhenqiang; Hölscher, Christian; Zhang, Zijuan","year":2025,"journal":"Molecular neurobiology, 62(9), 11920-11934","doi":"10.1007/s12035-025-05037-7","pmid":"40338455","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12361","title":"Knockdown of CXCL13 Improves Vascular Remodeling, Reduces Blood Pressure and Protects the Heart in a Hypertensive rat Model by Regulating the PF4V1/NF-κB Signaling Pathway.","authors":"Ma, Jie; Sun, Xiaoguang; Hu, Xianjun","year":2025,"journal":"Journal of cardiovascular pharmacology and therapeutics, 30, 10742484251351120","doi":"10.1177/10742484251351120","pmid":"41066312","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12362","title":"Tirzepatide administration improves cognitive impairment in HFD mice by regulating the SIRT3-NLRP3 axis.","authors":"Ma, Jingjing; Liu, Yuanyuan; Hu, Junya; Liu, Xingjing; Xia, Yin; Xia, Wenqing; Shen, Ziyang; Kong, Xiaocen; Wu, Xia; Mao, Li; Li, Qian","year":2025,"journal":"Endocrine, 87(2), 486-497","doi":"10.1007/s12020-024-04013-w","pmid":"39222203","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12363","title":"Comparison of the effects of Liraglutide, Tirzepatide, and Retatrutide on diabetic kidney disease in db/db mice.","authors":"Ma, Jun; Hu, Xiaoyan; Zhang, Wencheng; Tao, Mengyuan; Wang, Min; Lu, Weiping","year":2025,"journal":"Endocrine, 87(1), 159-169","doi":"10.1007/s12020-024-03998-8","pmid":"39212900","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12364","title":"Tirzepatide modulates gut microbiota homeostasis to protect against diabetic kidney disease.","authors":"Ma, Jun; Tao, Mengyuan; Zhang, Wencheng; Zhou, Li; Zhang, Henglu; Li, Fei; Zhang, Hongman; Yao, Di; Lu, Weiping; Wang, Min","year":2025,"journal":"Frontiers in molecular biosciences, 12, 1715024","doi":"10.3389/fmolb.2025.1715024","pmid":"41458627","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Eight weeks of tirzepatide treatment (10 nmol/kg) in diabetic db/db mice produced:\n\nMetabolic improvements: decreased fasting blood glucose, HbA1c, body weight, food intake, blood lipids, and liver function markers\n\nKidney protection: improved renal function markers (serum creatinine and urinary albumin/creatinine ratio)\n\nMicrobiome changes: reversed gut dysbiosis, increasing beneficial genera (Clostridium_sensu_stricto_1, Romboutsia) and reducing pathogenic genera (Erysipelatoclostridium, Bacteroides). These microbiome changes correlated significantly with kidney function markers.\n\nCritical validation: when gut microbiota was depleted with antibiotics prior to tirzepatide treatment (ABX-db/db-T group), the renoprotective effects were attenuated — demonstrating the gut microbiome is a necessary mediator of tirzepatide's kidney protection.","whyItMatters":"Diabetic kidney disease affects about 40% of people with diabetes and is the leading cause of kidney failure worldwide. Current treatments slow progression but don't stop it. If tirzepatide protects kidneys partly through gut bacteria, this opens entirely new treatment strategies — including combining tirzepatide with probiotics or dietary interventions that further optimize the microbiome. The antibiotic experiment is a particularly powerful piece of evidence because it shows causation, not just correlation.","specificNumbers":"","methodology":"Seven-week-old diabetic db/db mice and db/m controls were divided into three groups (db/db, db/db-T treated with tirzepatide, db/m controls). The treatment group received 10 nmol/kg tirzepatide injections for 8 weeks. An additional antibiotic-pretreated group (ABX-db/db-T) tested whether gut bacteria depletion affected tirzepatide's benefits. Assessments included biochemical markers (blood glucose, HbA1c, lipids, liver and kidney function), renal histopathology, and 16S rRNA gene sequencing for gut microbiota composition analysis.","limitations":"This is a mouse study using the db/db genetic model of diabetes, which may not perfectly replicate human diabetic kidney disease. The antibiotic depletion approach is a blunt tool — it eliminates all gut bacteria rather than specific populations. The specific mechanisms by which the altered microbiome protects kidneys are not fully identified (e.g., which microbial metabolites are involved). Sample sizes per group are not specified. The 8-week treatment period is relatively short for assessing kidney disease progression."},{"rthcId":"RPEP-12365","title":"Ghrelin/GHSR system attenuates collagen-induced arthritis in mice and ameliorates inflammation in human rheumatoid arthritis fibroblast-like synoviocytes.","authors":"Ma, Junxian; Zhang, Jinshan; Liu, Jie; Zhao, Jie; Wang, Xia; Li, Zhen; Lv, Tingting; Zhang, Yan","year":2025,"journal":"Biochemical pharmacology, 238, 116973","doi":"10.1016/j.bcp.2025.116973","pmid":"40339721","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12366","title":"Acupuncture and nutritional parallels in obesity: a narrative review of multi-pathway modulation of the microbiota-gut-brain axis.","authors":"Ma, Kun; Wang, Feifei; Zhang, Xinying; Guo, Liangqing; Huang, Yanqin","year":2025,"journal":"Frontiers in nutrition, 12, 1610814","doi":"10.3389/fnut.2025.1610814","pmid":"40851901","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review proposes an integrative framework connecting acupuncture to obesity treatment through the microbiota-gut-brain axis, identifying shared targets with dietary interventions:\n\n- Short-chain fatty acids (SCFAs) produced by gut bacteria\n- Glucagon-like peptide-1 (GLP-1) — the same peptide hormone targeted by semaglutide and other obesity drugs\n- G protein-coupled receptors, particularly GPR43, which mediates SCFA and metabolic signaling\n\nAcupuncture is proposed to improve microbial diversity, enhance gut barrier integrity, regulate nutrient-derived signaling molecules, and influence appetite control and inflammatory responses through neural, endocrine, and immune networks within the gut-brain axis.","whyItMatters":"As GLP-1 receptor agonists become blockbuster drugs for obesity, understanding non-pharmacological approaches that may modulate the same peptide signaling pathways is valuable. If acupuncture genuinely enhances endogenous GLP-1 release or gut peptide signaling, it could serve as a complementary therapy — potentially improving outcomes when combined with dietary modifications or reducing reliance on expensive medications.","specificNumbers":"","methodology":"This is a narrative review synthesizing published research on acupuncture's effects on gut microbiota, gut barrier function, peptide hormone signaling (particularly GLP-1), and metabolic outcomes in the context of obesity. The review draws parallels between acupuncture mechanisms and dietary/nutritional interventions that target the same pathways.","limitations":"This is a narrative review presenting a conceptual framework rather than systematic evidence. The quality and rigor of the underlying acupuncture studies cited are variable. Direct evidence that acupuncture significantly modulates GLP-1 levels in humans is limited. The proposed mechanisms are largely speculative, drawing parallels between acupuncture effects and known nutritional pathways without definitive mechanistic proof. Sham-controlled acupuncture trials for obesity have shown mixed results."},{"rthcId":"RPEP-12367","title":"Liraglutide improves cognition function in streptozotocin-induced diabetic rats by downregulating β-secretase and γ-secretase and alleviating oxidative stress in HT-22 cells.","authors":"Ma, Lou-Yan; Liu, Song-Fang; Ma, Zheng-Quan; Guo, Ya-Gang; Li, Mo; Gao, Yuan; Wen, Yu-Ting; Niu, Yu; Sui, Hai-Xia; Li, Bao-Shan; Li, Ya; Lv, Ya-Li; Huang, Yao; Zhai, Jia-Jia","year":2025,"journal":"Endocrine journal, 72(3), 285-294","doi":"10.1507/endocrj.EJ23-0723","pmid":"39647916","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12368","title":"Biological Properties of Arginine-rich Peptides and their Application in Cargo Delivery to Cancer.","authors":"Ma, Minghai; Zhao, Ruizhao; Li, Xing; Jing, Minxuan; Song, Rundong; Fan, Jinhai","year":2025,"journal":"Current drug delivery, 22(4), 387-400","doi":"10.2174/1567201820666230417083350","pmid":"37073158","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Arginine-rich cell-penetrating peptides exhibit higher transmembrane efficiency compared to other CPP types due to bidentate bonding between the guanidinium groups of arginine residues and negatively charged components on cell surfaces. This creates a particularly strong and specific interaction with cell membranes.\n\nA second critical function is endosome escape: when peptides are taken up by cells through endocytosis, they typically become trapped in endosomes that eventually fuse with lysosomes for degradation. Arginine-rich CPPs can disrupt endosomal membranes, allowing the delivered cargo — drugs, nucleic acids, or macromolecules — to escape into the cytoplasm where it can exert its therapeutic effect.","whyItMatters":"Many potent anticancer drugs and therapeutic nucleic acids fail in the clinic because they can't cross cell membranes to reach their intracellular targets. Cell-penetrating peptides solve this fundamental delivery problem. Arginine-rich CPPs are among the most promising because they combine two essential functions: efficient membrane crossing and endosome escape. Understanding their design principles enables the development of more effective drug delivery systems for cancer and potentially other diseases.","specificNumbers":"","methodology":"This is a review article summarizing 30 years of research on arginine-rich cell-penetrating peptides. The review covers the biological properties, design principles, membrane penetration mechanisms (including the role of guanidinium-membrane interactions), endosome escape mechanisms, and biomedical applications in cancer drug delivery and tumor biosensing.","limitations":"As a review article, this paper synthesizes existing research without presenting new data. Many CPP applications described remain at the preclinical stage. Key challenges not fully resolved include CPP selectivity (they can enter both healthy and cancer cells), potential toxicity at high concentrations, and the complexity of translating in vitro membrane penetration into effective in vivo tumor delivery. The review focuses on arginine-rich CPPs and may not capture the full landscape of CPP diversity."},{"rthcId":"RPEP-12369","title":"Irisin and liraglutide combination therapy mitigates myocardial reperfusion injury in obese rats: Role of endoplasmic reticulum stress and apoptosis.","authors":"Ma, Tao; Wang, Junyu; Sun, Guishun; Li, Kunlin; Qu, Haiyan; Wang, Yibo; Li, Shiwen; Wu, Bian","year":2025,"journal":"Archives of biochemistry and biophysics, 768, 110370","doi":"10.1016/j.abb.2025.110370","pmid":"40049268","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12370","title":"Smart self-assembled peptide-based hydrogels: Mechanism, design and biomedical applications.","authors":"Ma, Tao; Yu, Yi; Gao, Yijun; Jiang, Shanshan; Ge, Wenhui; Zeng, Yiyu; Wang, Xinying; Li, Shuangjiang; Xie, Xiaoyan; Guan, Gaopeng","year":2025,"journal":"Colloids and surfaces. B, Biointerfaces, 253, 114704","doi":"10.1016/j.colsurfb.2025.114704","pmid":"40300283","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12371","title":"Distinct effects of semaglutide and tirzepatide on metabolic and inflammatory gene expression in brown adipose tissue of mice fed a high-fat, high-fructose diet.","authors":"Ma, Tianyi; Song, Fanfan; Pan, Yongning; He, Ying; Cao, Xinming; Zhang, Yan; Song, Guangyao; Ren, Luping","year":2025,"journal":"Frontiers in nutrition, 12, 1659233","doi":"10.3389/fnut.2025.1659233","pmid":"41019552","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Both semaglutide and tirzepatide reduced body weight, improved lipid profiles, and enhanced insulin sensitivity in obese mice. However, their transcriptomic effects on brown adipose tissue were dramatically different: semaglutide modulated 467 differentially expressed genes (199 down, 268 up) compared to only 40 for tirzepatide (20 down, 20 up).\n\nThree shared targets were identified (Cyp1a1, Hsd11b1, Atp1a3) that enhance insulin sensitivity and metabolism. Tirzepatide uniquely modulated three additional targets — Tfrc (transferrin receptor, involved in iron metabolism), Ptger4 (prostaglandin receptor, anti-inflammatory), and Il1b (interleukin-1β, a key inflammatory mediator) — potentially explaining tirzepatide's enhanced anti-inflammatory and metabolic regulatory effects compared to GLP-1-only agonists.","whyItMatters":"The clinical observation that tirzepatide produces greater weight loss than semaglutide in head-to-head trials has raised questions about what the additional GIP receptor activation contributes beyond GLP-1 effects alone. This study provides molecular-level answers: tirzepatide modulates distinct anti-inflammatory genes in brown fat that semaglutide does not, suggesting the dual-receptor approach offers qualitatively different — not just quantitatively stronger — metabolic effects. These molecular targets could inform the development of next-generation obesity drugs.","specificNumbers":"","methodology":"Twenty-eight male C57BL/6J mice were divided into four groups: standard diet control (n=7) and three high-fat, high-fructose diet groups receiving saline, semaglutide, or tirzepatide (n=7 each) via subcutaneous injection for 7 weeks. Researchers assessed metabolic parameters (body weight, glucose, lipids, insulin), BAT morphology, and performed RNA sequencing on BAT with bioinformatic analysis (GO, KEGG, PPI). Key findings were validated by RT-qPCR.","limitations":"This is a mouse study, and brown fat biology differs between mice and humans — humans have much less BAT relative to body weight. The study used a 7-week treatment period, which may not capture long-term transcriptomic adaptations. With n=7 per group, statistical power for detecting small gene expression changes is limited. The functional significance of the identified gene targets was inferred from bioinformatics rather than directly validated experimentally (e.g., through gene knockout studies). Drug doses may not be directly comparable between semaglutide and tirzepatide in mouse models."},{"rthcId":"RPEP-12372","title":"Functionalized peptide hydrogels: enabling dynamic stage-adaptive modulation for wound healing.","authors":"Ma, Xi-Kun; Peng, Qi; Miao, Gui-Hua; Zhang, Xiu-Zhen","year":2025,"journal":"Frontiers in cell and developmental biology, 13, 1710175","doi":"10.3389/fcell.2025.1710175","pmid":"41311649","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Functionalized peptide hydrogels can be engineered to address all five key phases of wound healing through stage-specific bioactivities. Antimicrobial peptides like EPL, LL37, and TCP-25 not only kill pathogens but also direct macrophage behavior to reduce excessive inflammation. Angiogenic factors (VEGF, SDF-1) can be sustainably released from the hydrogel to promote new blood vessel growth. MMP-responsive components balance collagen deposition and degradation during tissue remodeling, while integrin-binding motifs like RGD enhance cell adhesion and migration to accelerate skin regrowth.\n\nThese hydrogels possess self-healing properties, can be injected through narrow openings, and respond to microenvironmental cues including pH changes, enzyme activity, and reactive oxygen species (ROS) levels — allowing them to adapt their therapeutic activity to the dynamic conditions within a healing wound.","whyItMatters":"Chronic wounds — including diabetic ulcers, pressure sores, and surgical wounds that won't heal — affect millions of people and cost healthcare systems billions annually. Current wound dressings are largely passive. A dressing that can actively participate in healing by killing bacteria, reducing inflammation, and promoting tissue repair at each stage could dramatically improve outcomes for patients with difficult-to-heal wounds.","specificNumbers":"","methodology":"This is a review article that synthesizes research on functionalized peptide hydrogel design, covering molecular programming strategies, bioactive components, and responsive mechanisms. It draws from in vitro and in vivo studies across the wound healing field to present a comprehensive picture of how peptide hydrogels can be engineered for stage-adaptive wound management.","limitations":"This is a review article, not a clinical study. Most of the technologies described are at the preclinical (lab and animal) stage. Translating multi-functional peptide hydrogels to clinical use faces challenges including manufacturing complexity, cost, regulatory approval for combination products, and demonstrating that responsive behaviors work predictably in diverse real-world wound environments. Long-term stability and shelf life of functionalized hydrogels are practical concerns not fully addressed."},{"rthcId":"RPEP-12373","title":"Endothelial progenitor cells have high predictive value for ventricular remodeling after percutaneous coronary intervention in acute myocardial infarction.","authors":"Ma, Yongxiang; Niu, Lijian; Zhang, Jing; Yu, Fei; Huang, Wenjun","year":2025,"journal":"Coronary artery disease, 36(5), 365-372","doi":"10.1097/MCA.0000000000001461","pmid":"39679591","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12374","title":"Serum Interleukin-8 Levels Identify Non-Atrial Fibrillation Patients at Risk for Catheterization-Confirmed Diastolic Dysfunction: A Retrospective Cohort Study.","authors":"Ma, Zhiyuan; Yang, Zhiqiang; Ji, Xiaotong; Shi, Meijing; Li, Lizhuo; Zhao, Qingzhen; Zhen, Yuzhi; Liu, Chao","year":2025,"journal":"Journal of cardiovascular translational research, 18(6), 1818-1829","doi":"10.1007/s12265-025-10712-0","pmid":"41118041","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12375","title":"Metabolic and bariatric surgery versus glucagon-like peptide-1 receptor agonist therapy: A comparison of cardiovascular outcomes in patients with obesity.","authors":"Maan, Soban; Sohail, Amir H; Sulaiman, Samia Aziz; Mansoor, Linta; Cohen, Ethan M; Adekolu, Ayowumi A; Abunnaja, Salim; Szoka, Nova; Tabone, Lawrence E; Thakkar, Shyam; Singh, Shailendra","year":2025,"journal":"American journal of surgery, 242, 116242","doi":"10.1016/j.amjsurg.2025.116242","pmid":"39965476","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12376","title":"Thymosin Beta-4 Modulates Cardiac Remodeling by Regulating ROCK1 Expression in Adult Mammals.","authors":"Maar, Klaudia; Thatcher, Jeffrey E; Karpov, Egor; Rendeki, Szilard; Gallyas, Ferenc; Bock-Marquette, Ildiko","year":2025,"journal":"International journal of molecular sciences, 26(9)","doi":"10.3390/ijms26094131","pmid":"40362372","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Following coronary ligation in adult mice, systemic TB4 injection led to a significant increase in miR-139-5p expression in heart tissue. The researchers identified ROCK1 as a downstream target of this miRNA pathway. Using real-time PCR, Western blot, and immunostaining in both mouse hearts and human cardiac cells, they confirmed that TB4 modulates ROCK1 protein levels both in vivo and in vitro.\n\nAdditionally, TB4 appeared to reverse or inhibit the transformation of fibroblasts into myofibroblasts — the cells primarily responsible for pathological scarring in the heart. The downstream mechanisms by which TB4 acts through ROCK1 were found to be cell-type specific, suggesting nuanced regulatory effects across different cardiac cell populations.","whyItMatters":"Heart attacks affect millions of people annually, and the scar tissue that forms afterward is a leading cause of heart failure. Current treatments can open blocked arteries but cannot regenerate damaged heart muscle or prevent scarring. TB4's ability to reduce pathological scarring through a defined molecular mechanism (ROCK1 regulation) provides a concrete therapeutic target. Since ROCK1 inhibitors are already being studied for various cardiac conditions, TB4 may offer a peptide-based approach to achieve similar benefits.","specificNumbers":"","methodology":"Researchers performed permanent coronary artery ligation in adult mice to induce heart attacks, then administered TB4 via systemic injection. MiRNA profiling was conducted on heart tissue from TB4-treated and untreated mice to identify differentially expressed microRNAs. Target analysis identified ROCK1 as a candidate protein. Validation was performed using real-time PCR, Western blot, and immunostaining in both adult mouse hearts (in vivo) and human cardiac cells (in vitro) to confirm TB4's effect on ROCK1 expression and fibroblast-to-myofibroblast transformation.","limitations":"The study was conducted in mouse models and human cell lines, not in human patients, so clinical translation is uncertain. The permanent coronary ligation model creates more severe damage than most human heart attacks (where reperfusion therapy is standard). The study identified an association between TB4 and ROCK1 modulation but the precise mechanism — whether direct or indirect — remains to be fully elucidated. Sample sizes for the animal experiments were not specified in the abstract."},{"rthcId":"RPEP-12377","title":"Scorpion venoms from the Buthidae family: A dual study of proteomic composition and anticancer potentials.","authors":"Mabunda, Isac G; Offor, Benedict C; Muller, Beric; Motadi, Lesetja R; Piater, Lizelle A","year":2025,"journal":"Toxicon : official journal of the International Society on Toxinology, 266, 108542","doi":"10.1016/j.toxicon.2025.108542","pmid":"40819823","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12378","title":"Medications for Obstructive Sleep Apnea.","authors":"Macanian, Jason; Schechter, Noah; Frishman, William H","year":2025,"journal":"Cardiology in review","doi":"10.1097/CRD.0000000000001148","pmid":"41403009","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12379","title":"Pain persists in mice lacking both Substance P and CGRPα signaling.","authors":"MacDonald, Donald Iain; Jayabalan, Monessha; Seaman, Jonathan T; Balaji, Rakshita; Nickolls, Alec R; Chesler, Alexander Theodore","year":2025,"journal":"eLife, 13","doi":"10.7554/eLife.93754","pmid":"40100256","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12380","title":"Non arteritic ischemic optic neuropathy in a patient taking semaglutide: Is there a relation? A case report and a review of the literature.","authors":"Maceroni, Martina; Sasso, Paola; Giarletti, Matteo; Bruno, Valentina; Minnella, Angelo Maria","year":2025,"journal":"European journal of ophthalmology, 35(4), NP10-NP15","doi":"10.1177/11206721251331655","pmid":"40183385","tags":[],"studyType":"case report + literature review","evidenceStrength":"very low","keyFinding":"A diabetic patient developed non-arteritic anterior ischemic optic neuropathy (NAION) — a condition that causes sudden, painless vision loss due to reduced blood flow to the optic nerve — while taking semaglutide. The authors reviewed the existing literature on this possible association and found conflicting results: the original semaglutide clinical trials did not show increased NAION risk, but a subsequent retrospective cohort study suggested a possible link. The overall evidence remains controversial, with studies presenting opposing conclusions.","whyItMatters":"With tens of millions of people now taking GLP-1 receptor agonists like semaglutide for diabetes and weight loss, even rare side effects become significant public health questions. NAION, while uncommon, causes irreversible vision loss. If GLP-1 drugs increase NAION risk — even slightly — this would affect risk-benefit calculations for millions of patients. The conflicting evidence makes this a clinically urgent question that requires larger, well-designed studies to resolve.","specificNumbers":"1 case reported · Clinical trials: no significant NAION increase · 1 retrospective study suggested association · Multiple subsequent studies with conflicting results","methodology":"The authors present a single case report of NAION in a diabetic patient on semaglutide and conduct a narrative review of published literature examining the potential association between GLP-1 receptor agonists and NAION, including original clinical trial data and subsequent observational studies.","limitations":"This is a single case report, which cannot establish causation. The patient had diabetes — itself a risk factor for NAION — making it impossible to attribute the event specifically to semaglutide. The literature review is narrative, not systematic, and the existing evidence is conflicting with no definitive answer. Confounding factors (diabetes, cardiovascular risk, other medications) complicate interpretation of all available studies."},{"rthcId":"RPEP-12381","title":"Persistence of Weekly Injectable Semaglutide Use in Patients with Diabetes Mellitus and Obesity: A Retrospective Follow-Up in Colombia.","authors":"Machado-Duque, Manuel Enrique; Gaviria-Mendoza, Andrés; Valladales-Restrepo, Luis Fernando; Machado-Alba, Jorge Enrique","year":2025,"journal":"Drugs - real world outcomes, 12(4), 615-622","doi":"10.1007/s40801-025-00518-6","pmid":"41042496","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12382","title":"Glucagon-Like Peptide 1 Receptor Agonist Stimulation Inhibits Laser-Induced Choroidal Neovascularization by Suppressing Intraocular Inflammation.","authors":"Machida, Akira; Suzuki, Keiji; Nakayama, Takafumi; Miyagi, Sugao; Maekawa, Yuki; Murakami, Ryuya; Uematsu, Masafumi; Kitaoka, Takashi; Oishi, Akio","year":2025,"journal":"Investigative ophthalmology & visual science, 66(5), 15","doi":"10.1167/iovs.66.5.15","pmid":"40332908","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12383","title":"An Evolutionary Loss of Parental Care in Stickleback Is Associated with Differences in the Activity, but Not the Number, of Neuropeptidergic Neurons in the Preoptic Area.","authors":"Maciejewski, Meghan F; Fischer, Eva K; Bell, Alison M; Maciejewski, Meghan","year":2025,"journal":"Brain, behavior and evolution, 100(3), 171-182","doi":"10.1159/000545350","pmid":"40159322","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12384","title":"Semaglutide: a key medication for managing cardiovascular-kidney-metabolic syndrome.","authors":"MacIsaac, Richard J","year":2025,"journal":"Future cardiology, 21(9), 663-683","doi":"10.1080/14796678.2025.2511412","pmid":"40458885","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12385","title":"Emulating real-world GLP-1 efficacy in type 2 diabetes through causal learning and virtual patients.","authors":"MacLellan, Calum Robert; Petkov, Hristo; McKeag, Conor; Dong, Feng; Lowe, David John; Maguire, Roma; Moschoyiannis, Sotiris; Armes, Jo; Skene, Simon; Finlinson, Alastair; Sainsbury, Christopher","year":2025,"journal":"PLOS digital health, 4(7), e0000927","doi":"10.1371/journal.pdig.0000927","pmid":"40690490","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12386","title":"Semaglutide for the treatment of MASH: reaching into the ESSENCE of cardio-metabolic health?","authors":"Mademlis, Christos; Patoulias, Dimitrios; Koufakis, Theocharis; Teperikidis, Eleftherios; Giouleme, Olga; Doumas, Michael","year":2025,"journal":"Expert review of clinical pharmacology, 18(10), 1-5","doi":"10.1080/17512433.2025.2573785","pmid":"41070406","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12387","title":"An overview of recent developments in clinical trials of anti-diabetic drugs.","authors":"Madhuri, Yeduvaka; Saifullah, Qazi; Pandey, Manisha; Bhattamisra, Subrat K","year":2025,"journal":"Panminerva medica, 67(2), 87-100","doi":"10.23736/S0031-0808.25.05314-5","pmid":"40457780","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12388","title":"The promise of glucagon-like peptide 1 receptor agonists (GLP-1RA) for the treatment of obesity: a look at phase 2 and 3 pipelines.","authors":"Madsbad, Sten; Holst, Jens J","year":2025,"journal":"Expert opinion on investigational drugs, 34(3), 197-215","doi":"10.1080/13543784.2025.2472408","pmid":"40022548","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12389","title":"First evidence of efficacy of peptides targeting the pUL56-pUL89 interaction domain of the human cytomegalovirus terminase complex.","authors":"Mafi, Sarah; Poyet, Jean-Luc; Alain, Sophie; Ligat, Gaëtan; Hantz, Sébastien","year":2025,"journal":"Antiviral research, 242, 106259","doi":"10.1016/j.antiviral.2025.106259","pmid":"40816464","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12390","title":"Liraglutide improves depressive and cognitive deficits in a high-fat diet rat model of obesity: the role of hippocampal autophagy and the PI3K/Akt/mTOR pathway.","authors":"Magdy, Yosra M; Kamar, Sherif A; Habib, Mohamed Z; Rady, Hagar Yousry; Rabei, Mohammed R; Khedr, Sara","year":2025,"journal":"Psychopharmacology, 242(12), 2801-2816","doi":"10.1007/s00213-025-06834-7","pmid":"40526304","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Chronic liraglutide treatment (300 μg/kg/day subcutaneous for 28 days) in high-fat diet obese rats produced multiple neuropsychiatric improvements:\n\n- Reversed depressive-like behavior in sucrose preference test and forced swimming test\n- Improved cognitive deficits in Morris water maze test\n- Increased hippocampal BDNF, PI3K, Akt, phospho-Akt, and phospho-mTOR expression\n- Downregulated autophagy markers (Beclin-1, LC3)\n- Reduced inflammatory markers (TNF-α, IL-6)\n- Ameliorated HFD-induced hippocampal neurodegeneration\n\nThe benefits were mediated through restoration of PI3K/Akt/mTOR signaling and reduction of excessive autophagy-mediated neurodegeneration.","whyItMatters":"Depression and cognitive impairment are common but often overlooked complications of obesity. The finding that a GLP-1 drug improves these psychiatric symptoms — through specific brain mechanisms — suggests that GLP-1 drugs may offer mental health benefits beyond weight management. This is particularly relevant as millions of patients report improved mood and cognition on these medications, and clinical trials are exploring GLP-1 drugs for neurodegenerative diseases.","specificNumbers":"","methodology":"Rats were fed a high-fat diet to induce obesity, then received chronic liraglutide (300 μg/kg/day subcutaneous) for 28 days. Behavioral assessments included the sucrose preference test and forced swimming test (depression), and Morris water maze (cognition). Hippocampal tissue was analyzed for BDNF expression, PI3K/Akt/mTOR pathway markers, autophagy markers (Beclin-1, LC3), inflammatory markers (TNF-α, IL-6), and histopathological changes.","limitations":"This was an animal study using a high-fat diet model, and rat brain responses may not fully reflect human neuropsychiatric conditions. The 28-day treatment period is relatively short. The behavioral tests used are standard but cannot fully capture the complexity of human depression and cognition. The study did not assess whether benefits persisted after liraglutide was stopped, and the specific dose may not correspond to human therapeutic levels."},{"rthcId":"RPEP-12391","title":"Sex-specific involvement of calcitonin gene-related peptide signaling for pain in experimental autoimmune encephalomyelitis.","authors":"Maguire, Aislinn D; Friedman, Timothy N; Willis, Elyse; Gosse, Elise; Kuypers, Grayden; Andrade, Dania Villarreal; Stephens, Camille; Tenorio, Gustavo; Plemel, Jason R; Kerr, Bradley J","year":2025,"journal":"Pain reports, 10(6), e1350","doi":"10.1097/PR9.0000000000001350","pmid":"41169930","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12392","title":"Cardiovascular outcomes with semaglutide by severity of chronic kidney disease in type 2 diabetes: the FLOW trial.","authors":"Mahaffey, Kenneth W; Tuttle, Katherine R; Arici, Mustafa; Baeres, Florian M M; Bakris, George; Charytan, David M; Cherney, David Z I; Chernin, Gil; Correa-Rotter, Ricardo; Gumprecht, Janusz; Idorn, Thomas; Pugliese, Giuseppe; Rasmussen, Ida Kirstine Bull; Rasmussen, Søren; Rossing, Peter; Sokareva, Ekaterina; Mann, Johannes F E; Perkovic, Vlado; Pratley, Richard","year":2025,"journal":"European heart journal, 46(12), 1096-1108","doi":"10.1093/eurheartj/ehae613","pmid":"39211948","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12393","title":"GLP-1 agonists-induced autoimmune pancreatitis.","authors":"Mahajne, Jasmin; Angarola, Ernestina; Della Torre, Emanuel; Lanzillotta, Marco","year":2025,"journal":"BMJ case reports, 18(9)","doi":"10.1136/bcr-2025-267811","pmid":"40992778","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12394","title":"Headline: Fracture Risk in Type 2 Diabetes: Systematic Review of Cardiovascular Outcome Trials with Glucagon Like Peptide Receptor Agonists.","authors":"Mahalingasivam, Aksayan Arunanthy; Rasmussen, Nicklas Højgaard-Hessellund","year":2025,"journal":"Current osteoporosis reports, 23(1), 38","doi":"10.1007/s11914-025-00937-y","pmid":"41026248","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"After screening 797 records and including 20 studies from cardiovascular outcome trials, the review found that preclinical evidence supports potential bone-protective effects of GLP-1 receptor agonists, including increased bone mass, improved bone microarchitecture, and reduced bone resorption. However, human clinical evidence was inconsistent — some studies suggested possible fracture risk reduction with long-term GLP-1 RA therapy, while others did not confirm this benefit. The authors concluded that more targeted research is needed to clarify the role of these drugs in bone metabolism and fracture prevention for people with type 2 diabetes.","whyItMatters":"People with type 2 diabetes already face an elevated risk of fractures despite often having normal bone density. GLP-1 receptor agonists like semaglutide and liraglutide are now among the most widely prescribed medications globally — understanding whether they help or harm bone health could influence treatment decisions for millions of patients.","specificNumbers":"","methodology":"The researchers conducted a systematic literature search that identified 797 records. After removing 154 duplicates, they screened 643 records and ultimately included 20 studies that met their inclusion criteria. The included studies were cardiovascular outcome trials involving GLP-1 receptor agonists in people with type 2 diabetes, with fracture data examined as a secondary outcome.","limitations":"The review relied on fracture data from cardiovascular outcome trials, which were not designed to study bone health as a primary endpoint. Fracture reporting in these trials may have been inconsistent or incomplete. The included studies varied in drug type, dosing, and follow-up duration, making direct comparisons difficult."},{"rthcId":"RPEP-12395","title":"Comparing High- Versus Low-Dose Entresto in Heart Failure Patients: A 2025 Meta-Analysis.","authors":"Maharaj, Akshay; Bidhesi, Sajay; Jaggernauth, Sheneel; Ramoutar, Shyam R; Lutchmedial, Rajiv N; Maharaj, Matthew A; Lutchman, Aaron; Bhandari, Amit; Khan, Adam S; Ferdaus, Ramisa; Remanan, Aparna; Husain, Mohammad M; Bhagwandeen, Sinead N; Bhagwandeen, Victoria","year":2025,"journal":"Cureus, 17(8), e90499","doi":"10.7759/cureus.90499","pmid":"41104272","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12396","title":"Effect of Ivabradine on Heart Failure: A 2024 Meta-Analysis.","authors":"Maharaj, Akshay; Maturasingh, Matthew B; Khangembam, Alvin; Bidhesi, Sajay N; Rai, Shanzey; Garness, Kamille A; Khadoo, Nick; Tutwala, Nimish; Khan, Natalia A; Ramsarran, Jonelle J; Bhandari, Amit; Rajbhandari, Pranaya; Htet, Khin Linn; Husain, Mohammad M; Bhagwandeen, Sinead N; Rattan, Keston","year":2025,"journal":"Cureus, 17(1), e77346","doi":"10.7759/cureus.77346","pmid":"39944426","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12397","title":"Use of Spironolactone for the Treatment of Heart Failure With Preserved Ejection Fraction: Efficacy and Clinical Implications in Light of Recent Evidence.","authors":"Maharjan, Reeju; Akintunde, Damilare M; Reddy Narla, Sai Jahnu Sree; Baltodano Garcia, Diana C; Mekala, Sai Charan; Srinivasan, Sahana; Nath, Tuheen Sankar","year":2025,"journal":"Cureus, 17(6), e85908","doi":"10.7759/cureus.85908","pmid":"40656394","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12398","title":"Protective effect of Dulaglutide, a GLP1 agonist, on acetic acid-induced ulcerative colitis in rats: involvement of GLP-1, TFF-3, and TGF-β/PI3K/NF-κB signaling pathway.","authors":"Mahdy, Raghda N El; Nader, Manar A; Helal, Manar G; Abu-Risha, Sally E; Abdelmageed, Marwa E","year":2025,"journal":"Naunyn-Schmiedeberg's archives of pharmacology, 398(5), 5611-5628","doi":"10.1007/s00210-024-03631-5","pmid":"39579211","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12399","title":"Inflammatory optic neuritis and scleritis following commencement of semaglutide: a case report.","authors":"Maher, Clare B; Guo, Brad; Dunlop, Anthony A","year":2025,"journal":"Journal of surgical case reports, 2025(11), rjaf937","doi":"10.1093/jscr/rjaf937","pmid":"41306396","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12400","title":"GLP-1 Receptor Agonists in Hidradenitis Suppurativa: A Novel Therapeutic Approach for Hidradenitis Suppurativa and Its Comorbidities.","authors":"Maher, Sawyeh; Gold, Michael H","year":2025,"journal":"Journal of drugs in dermatology : JDD, 24(12), 1174-1180","doi":"10.36849/JDD.9062","pmid":"41329148","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12401","title":"The Synergistic Treatment of Heart and Kidney Disease.","authors":"Mahfoud, Felix; Götzinger, Felix; Kramann, Rafael; Marx, Nikolaus; Schwenger, Vedat","year":2025,"journal":"Deutsches Arzteblatt international","doi":"10.3238/arztebl.m2025.0131","pmid":"40801823","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12402","title":"An in-silico analysis of the interaction between selected honey bee venom peptides and the murine MHC-hMOG37-46 complex for investigating potential therapeutic approaches in multiple sclerosis.","authors":"Mahnam, Karim; Razavi, Seyedeh Fahimeh; Shakhsi-Niaei, Mostafa","year":2025,"journal":"Journal of biomolecular structure & dynamics, 1-25","doi":"10.1080/07391102.2025.2576725","pmid":"41200929","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12403","title":"Association of Baseline Comorbidities With First-Year Adherence to GLP-1 Receptor Agonists in Patients With Diabetes or Obesity: A Retrospective Cohort Study.","authors":"Mai, Ziyang; Kornak, John; Dufault, Suzanne M; Strand, Michael W; Reikes, Andrew R; Watanabe, Jonathan H","year":2025,"journal":"The Annals of pharmacotherapy, 10600280251384637","doi":"10.1177/10600280251384637","pmid":"41355396","tags":[],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"Among 69,049 adults who started GLP-1 receptor agonists, comorbidities significantly influenced first-year adherence. Patients with diabetes who also had hyperlipidemia (OR 1.17), chronic kidney disease (OR 1.14), or hypertension (OR 1.06) were more likely to stay on their GLP-1 medication. Conversely, cardiovascular disease (OR 0.90) and digestive side effects (OR 0.94) reduced adherence.\n\nSimilar patterns held for patients with obesity. Findings were consistent across different GLP-1 RA brands, suggesting these adherence patterns are class-wide rather than drug-specific.","whyItMatters":"With tens of millions of people now taking GLP-1 drugs, understanding who stays on them is critical. This study reveals that patients with more health conditions (except cardiovascular disease) are actually more adherent — possibly because they perceive greater benefit. Digestive side effects remain a key barrier, highlighting the need for better side effect management to improve persistence.","specificNumbers":"n=69,049 · 59.3% with diabetes · 74.4% with obesity · Hyperlipidemia OR 1.17 · CKD OR 1.14 · ASCVD OR 0.90 · GI adverse events OR 0.94","methodology":"Retrospective cohort study using the University of California Health Data Warehouse. Adults initiating GLP-1 RAs between 2018–2023 were identified. First-year adherence was the primary outcome, analyzed against baseline comorbidities and digestive adverse events using logistic regression. Analyses were stratified by indication (diabetes vs. obesity) and drug subtype.","limitations":"Observational design cannot establish causation. Adherence was measured from health system records, which may not capture medications obtained elsewhere. The study cannot determine patient motivations for continuation or discontinuation. University of California health system patients may not be representative of all GLP-1 users nationally."},{"rthcId":"RPEP-12404","title":"Exceptional tumor-free survival of a patient with metastatic intrahepatic cholangiocarcinoma after surgery and personalized peptide vaccination: revisiting a striking case.","authors":"Maia, Ana; Schuhmacher, Juliane; Nadalin, Silvio; Königsrainer, Alfred; Thiel, Karolin; Nelde, Annika; Zinser, Raphael S; Schroeder, Christopher; Mattern, Sven; Singer, Stephan; Bösmüller, Hans; Rammensee, Hans-Georg; Löffler, Markus W; Gouttefangeas, Cécile","year":2025,"journal":"Journal for immunotherapy of cancer, 13(10)","doi":"10.1136/jitc-2025-012107","pmid":"41067882","tags":[],"studyType":"case report","evidenceStrength":"very low","keyFinding":"A patient with metastatic intrahepatic cholangiocarcinoma (bile duct cancer) — a typically fatal cancer with few treatment options — has remained tumor-free for more than 8 years after repeated surgery and two successive personalized peptide vaccines. Immune analysis revealed a dominant CD4+ T-cell response against vaccine antigens that persisted for years after the last vaccination, with immune cells infiltrating the tumor site. The patient also developed spontaneous immune responses against tumor neoantigens (CD4+ and CD8+ T cells), which may have contributed to the exceptional outcome. This case highlights both personalized peptide vaccination targeting non-mutated antigens and the central role of CD4+ T cells in antitumor immunity.","whyItMatters":"Cholangiocarcinoma is one of the most lethal cancers, with 5-year survival rates typically below 10% for advanced disease. This patient's 8+ year tumor-free survival after personalized peptide vaccination is extraordinary and suggests that the immune system can be trained to fight even highly aggressive cancers when given the right peptide targets. The finding that CD4+ T cells — often overshadowed by CD8+ \"killer\" T cells in cancer immunotherapy — played a dominant role challenges conventional thinking about antitumor immunity.","specificNumbers":"8+ years tumor-free · 2 successive personalized peptide vaccines · Dominant CD4+ T-cell response · Tumor neoantigen-specific CD4+ and CD8+ responses detected","methodology":"This is a long-term follow-up case report of a single patient who received repeated surgery and two personalized peptide vaccines for metastatic intrahepatic cholangiocarcinoma. Researchers performed in-depth functional immune cell analyses to characterize the T-cell responses against vaccine antigens and spontaneous tumor neoantigens, including assessment of tumor-site infiltration and persistence of immune responses over time.","limitations":"This is a single-patient case report — the most extreme form of individual evidence. It is impossible to determine from one case whether the peptide vaccines caused the exceptional outcome or whether this patient had unusually favorable biology. The combination of repeated surgery and vaccination makes it difficult to attribute the response to either intervention alone. Case reports of exceptional responders are subject to publication bias, as poor outcomes are rarely reported."},{"rthcId":"RPEP-12405","title":"Suicidal Thoughts and Self-injurious Behavior Associated With Glucagon- Like Peptide-1 Receptor Agonists - A Review.","authors":"Maideen, Naina Mohamed Pakkir; Al Rashid, Sulthan","year":2025,"journal":"Current drug safety, 20(3), 253-257","doi":"10.2174/0115748863301925240507044637","pmid":"38766830","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12406","title":"Glucagon Like Peptide-1 Receptor Agonists for Sarcopenia and Muscle Wasting Disorders: A Systematic Review of Efficacy and Mechanisms.","authors":"Maihemuti, Abudureheman; Cui, Can; Wang, Qianjin; Amuti, Reziwanguli; Chau, Wai Wang; Chai, Senlin; Zhang, Ning; Wong, Ronald Man Yeung; Ko, Ho; Kwok, Timothy Chi-Yui; Cheung, Wing-Hoi","year":2025,"journal":"Aging and disease","doi":"10.14336/AD.2025.1165","pmid":"41400575","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12407","title":"Tumor Microenvironment pH-Sensitive Peptidomimetics for Targeted Anticancer Drug Delivery.","authors":"Maity, Biswanath; Moorthy, Hariharan; Govindaraju, Thimmaiah","year":2025,"journal":"Biochemistry, 64(6), 1266-1275","doi":"10.1021/acs.biochem.4c00657","pmid":"40014813","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12408","title":"Cecropin anisaxin-2S has in vitro immunomodulatory, but not antiproliferative and antiviral properties.","authors":"Majstorović, Jovana; Arakelyan, Anush; Trumbić, Željka; Kamiš, Jan; Adamek, Mikolaj; Rončević, Tomislav; Čikeš Čulić, Vedrana; Kyslík, Jiří; Palus, Martin; Fiala, Ivan; Mladineo, Ivona","year":2025,"journal":"Frontiers in immunology, 16, 1567505","doi":"10.3389/fimmu.2025.1567505","pmid":"40391212","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12409","title":"Availability of Cardioprotective Medications for Type 2 Diabetes in the Medicaid Program.","authors":"Makam, Anil N; Bailey, Logan; Anderson, Nigel; Bellitti, Kathy; Skinner, Sasha; Nguyen, Oanh Kieu","year":2025,"journal":"Annals of internal medicine, 178(6), 808-818","doi":"10.7326/ANNALS-24-01449","pmid":"40258281","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12410","title":"Effect of pH, buffers, molarity, and temperature on solution state degradation of semaglutide using LC-HRMS: A preformulation protocol for peptide drug delivery.","authors":"Malgave, Adarsh; Akbar, Sideequl; Joseph, Anumol; Dande Aishwarya; Peraman, Ramalingam; Malayandi, Rajkumar","year":2025,"journal":"European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 214, 114780","doi":"10.1016/j.ejpb.2025.114780","pmid":"40490042","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12411","title":"Influence of Buffering Capacity, pH, and Temperature on the Stability of Semaglutide: A Preformulation Study.","authors":"Malgave, Adarsh; Akbar, Sideequl; Tiwari, Ayushi; Hande, Shamal; Joseph, Anumol; Malayandi, Rajkumar","year":2025,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 31(8), e70039","doi":"10.1002/psc.70039","pmid":"40635175","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12412","title":"Tirzepatide for sleep-disordered breathing in SURMOUNT-OSA: Time course and association with body weight.","authors":"Malhotra, Atul; Grunstein, Ronald R; Azarbarzin, Ali; Sands, Scott A; Dang, Xiangnan; Chakladar, Sujatro; Dunn, Julia P; Falcon, Beverly; Bednarik, Josef","year":2025,"journal":"Sleep medicine, 136, 106853","doi":"10.1016/j.sleep.2025.106853","pmid":"41135142","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12413","title":"Obesity Epidemic and Its Impact on Female Fertility: Current Understanding and Future Directions.","authors":"Malhotra, Radhika; Garcia de Paredes, Jessica; Smith, Alexandria; Chemerinski, Anat; Doshi, Dhvani; Morelli, Sara S","year":2025,"journal":"Cureus, 17(7), e87283","doi":"10.7759/cureus.87283","pmid":"40755647","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12414","title":"Devices to overcome the buccal mucosal barrier to administer therapeutic peptides.","authors":"Malhotra, Sahil; Lijnse, Thomas; Cearbhaill, Eoin O'; Brayden, David J","year":2025,"journal":"Advanced drug delivery reviews, 220, 115572","doi":"10.1016/j.addr.2025.115572","pmid":"40174726","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Engineered buccal (inner cheek) devices can overcome the mucosal permeability barrier to deliver therapeutic peptides through the mouth lining. These devices use multiple mechanisms — physical epithelial disruption, convection-based mass transfer, and combined physicochemical strategies — to achieve fast, efficient peptide absorption. Importantly, minimally invasive devices can be self-applied by patients and maintain the mucosal barrier integrity after use. The buccal route avoids both the harsh gastrointestinal environment and liver first-pass metabolism that limit oral peptide delivery.","whyItMatters":"Most peptide drugs require injection, which is a major barrier to patient acceptance. Oral delivery has poor bioavailability due to digestive degradation. Buccal delivery through the inner cheek offers a 'best of both worlds' solution — needle-free, no food restrictions, avoids stomach degradation and liver metabolism. If these devices succeed clinically, they could transform how peptide drugs like semaglutide, insulin, and others are administered.","specificNumbers":"Review covers physical disruption, convection-based transfer, and physicochemical strategies · buccal route avoids first-pass liver metabolism · no food/drink restrictions needed · minimally invasive self-applied devices · maintains barrier after exposure","methodology":"This is a comprehensive review examining buccal physiology, the permeability barrier to peptide absorption, and engineered device strategies to overcome it. The review analyzes device performance, manufacturing considerations, patient acceptability, and commercial viability for clinical translation of buccal peptide delivery.","limitations":"As a review, no new experimental data are presented. Most buccal peptide delivery devices are in preclinical or early development stages. Achieving consistent bioavailability across patients with varying mucosal conditions is a challenge. Patient comfort and long-term mucosal effects of repeated device use need assessment. Regulatory pathways for combination device-drug products are complex."},{"rthcId":"RPEP-12415","title":"Efficacy and safety of oral semaglutide as add-on therapy in poorly controlled type 2 diabetes on background SGLT2 inhibitors: a real-world, multi-center, retrospective, observational study (RYS2).","authors":"Malighetti, Maria E; Vescini, Fabio; Carpentieri, Maria; Altomari, Anna; Turchi, Federica; DA Porto, Andrea; Dauriz, Marco","year":2025,"journal":"Minerva endocrinology","doi":"10.23736/S2724-6507.25.04376-3","pmid":"41307513","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12416","title":"A Case Report: The Utility of Multimodality Imaging in the Diagnosis of Cardiac Sarcoidosis-Has It Surpassed the Need for a Biopsy?","authors":"Malik, Ali; Ippolito, Paul; Kundur, Sukruth Pradeep; Sivalokanathan, Sanjay","year":2025,"journal":"Reports (MDPI), 8(1)","doi":"10.3390/reports8010028","pmid":"40729241","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12417","title":"Design, Computational Assessment, and Experimental Characterization of a Self-Assembling Peptide Hydrogel.","authors":"Malik, Ashish; Fontana, Federico; Corvaglia, Valentina; Angione, Sara; Sala, Giulia; Agrello, Roberta; Gelain, Fabrizio","year":2025,"journal":"ACS applied bio materials, 8(8), 6772-6783","doi":"10.1021/acsabm.5c00285","pmid":"40759405","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12418","title":"Peptide-based indirect ELISA for salmon GnRH analogue detection: Enhanced sero-retention with chitosan nanoconjugation.","authors":"Malik, Mohd Ashraf; Bedekar, Megha Kadam; Bhat, Raja Aadil Hussain; Valsalam, Anisha; Varghese, Tincy; Jahageerdar, Shrinivas; Nayak, Sunil Kumar; Reang, Dhalongsaih; Gupta, Subodh","year":2025,"journal":"International journal of biological macromolecules, 333(Pt 2), 148970","doi":"10.1016/j.ijbiomac.2025.148970","pmid":"41232873","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12419","title":"Role of DPP-4 and NPY Family Peptides in Gastrointestinal Symptoms Associated with Obesity and Type 2 Diabetes Mellitus.","authors":"Malinauskas, Mantas; Paskeviciene, Deimante; Steponaitienė, Rūta; Gudaityte, Rita; Kupčinskas, Limas; Casselbrant, Anna; Maleckas, Almantas","year":2025,"journal":"Medicina (Kaunas, Lithuania), 61(3)","doi":"10.3390/medicina61030504","pmid":"40142315","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12420","title":"Clinical and Genetic Factors Associated with Non-Response to Erenumab.","authors":"Mallucci, Giulia; Terrazzino, Salvatore; Giacon, Martina; Cordella, Alberto; Cargnin, Sarah; Schankin, Christoph; Gobbi, Claudio; Zecca, Chiara","year":2025,"journal":"Journal of clinical medicine, 14(24)","doi":"10.3390/jcm14248922","pmid":"41464829","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12421","title":"A survey of hypothalamic phenotypes identifies molecular and behavioral consequences of MYT1L haploinsufficiency in male and female mice.","authors":"Maloney, Susan E; McCullough, Katherine B; Chaturvedi, Sneha M; Selmanovic, Din; Chase, Rebecca; Chen, Jiayang; Wu, Shanyun; Granadillo, Jorge L; Kroll, Kristen L; Dougherty, Joseph D","year":2025,"journal":"Hormones and behavior, 174, 105796","doi":"10.1016/j.yhbeh.2025.105796","pmid":"40729938","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12422","title":"Tirzepatide compared with semaglutide and 10-year cardiovascular disease risk reduction in obesity: post-hoc analysis of the SURMOUNT-5 trial.","authors":"Mamas, Mamas A; Bays, Harold; Li, Runjia; Upadhyay, Navneet; Irani, Tanya; Senyucel, Cagri; Dunn, Julia P; Liu-Seifert, Hong","year":2025,"journal":"European heart journal open, 5(5), oeaf117","doi":"10.1093/ehjopen/oeaf117","pmid":"40980721","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In participants with obesity and no prior cardiovascular disease, the average baseline 10-year CVD risk score was 9.3%. After 72 weeks of treatment:\n\n- Tirzepatide reduced predicted 10-year CVD risk by 2.4% (absolute reduction from baseline)\n- Semaglutide reduced predicted 10-year CVD risk by 1.4% (absolute reduction from baseline)\n- The difference was statistically significant (P < 0.001)\n\nProjected to the ~85 million treatment-eligible Americans without prior CVD, tirzepatide could potentially prevent ~2 million CVD events over 10 years, compared to ~1.15 million with semaglutide.","whyItMatters":"About two-thirds of obesity-related deaths are from cardiovascular disease. This head-to-head comparison suggests tirzepatide may offer meaningfully greater cardiovascular protection than semaglutide in obesity, which could influence treatment decisions for millions of people and potentially save hundreds of thousands of additional lives.","specificNumbers":"","methodology":"This was a post-hoc analysis of the SURMOUNT-5 trial, a Phase 3b open-label randomized trial comparing tirzepatide (10 or 15 mg) with semaglutide (1.7 or 2.4 mg) via weekly subcutaneous injection over 72 weeks. Predicted 10-year CVD risk scores were calculated at baseline and post-treatment. Population-level impact was estimated by extrapolating risk reductions to the eligible US population.","limitations":"This is a post-hoc analysis using predicted CVD risk scores, not actual observed cardiovascular events. The SURMOUNT-5 trial was open-label, which could introduce bias. The population projections assume that trial results would generalize to the entire US eligible population. The CVD risk prediction model may not fully capture the mechanisms through which these drugs reduce cardiovascular risk. The 72-week treatment period may not reflect long-term real-world medication adherence."},{"rthcId":"RPEP-12423","title":"Organ-specific response to [177Lu]DOTATATE peptide receptor radionuclide therapy (PRRT) assessed by sequential [68Ga]DOTATOC PET/CT in patients with metastatic small intestine neuroendocrine tumors.","authors":"Mamulashvili Bessac, Darejan; Baltzinger, Philippe; Poterszman, Nathan; Pham Van, Floriane; Collen, Cedric; Malouf, Gabriel G; Ouvrard, Eric; Kaseb, Ashjan; Porot, Clemence; Ben Abdelghani, Meher; Addeo, Pietro; Mertz, Luc; Goichot, Bernard; Imperiale, Alessio","year":2025,"journal":"Endocrine, 87(3), 1333-1341","doi":"10.1007/s12020-024-04138-y","pmid":"39714577","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12424","title":"Multimodal profiling of Pepcan-CB1 receptor structure-activity relationships: integrating molecular dynamics simulations, biological profiling, and the deep learning model MuMoPepcan.","authors":"Man, Hongyang; Bao, Huiming; Niu, Zhanyu; Zhang, Zhonghua; Simon, Jerine Peter; Yang, Tong; Li, Pengtao; Dong, Shouliang","year":2025,"journal":"Bioorganic chemistry, 165, 109027","doi":"10.1016/j.bioorg.2025.109027","pmid":"41005111","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12425","title":"Sexually dimorphic effects of angiopoietin-like 2 on energy metabolism and hypothalamic neuropeptide regulation.","authors":"Manceau, Romane; Anthony, Pinçon; Hryhorczuk, Cécile; Labbé, Pauline; Thorin-Trescases, Nathalie; Fulton, Stephanie; Thorin, Éric","year":2025,"journal":"International journal of obesity (2005), 49(6), 1116-1124","doi":"10.1038/s41366-025-01754-0","pmid":"40133699","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12426","title":"Binding kinetics, bias, receptor internalization and effects on insulin secretion in vitro and in vivo of a novel GLP-1R/GIPR dual agonist, HISHS-2001.","authors":"Manchanda, Yusman; Jones, Ben; Carrat, Gaelle; Ramchunder, Zenouska; Marchetti, Piero; Leclerc, Isabelle; Thennati, Rajamannar; Burade, Vinod; Natarajan, Muthukumaran; Shahi, Pradeep; Tomas, Alejandra; Rutter, Guy A","year":2025,"journal":"Diabetes, obesity & metabolism, 27(10), 5938-5949","doi":"10.1111/dom.16652","pmid":"40831316","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12427","title":"Binding Kinetics, Bias, Receptor Internalization and Effects on Insulin Secretion in vitro and in vivo of a Novel GLP-1R/GIPR Dual Agonist, HISHS-2001.","authors":"Manchanda, Yusman; Jones, Ben; Carrat, Gaelle; Ramchunder, Zenouska; Marchetti, Piero; Leclerc, Isabelle; Thennati, Rajamannar; Burade, Vinod; Natarajan, Muthukumaran; Shahi, Pradeep; Tomas, Alejandra; Rutter, Guy A","year":2025,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2025.01.13.632834","pmid":"39868265","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12428","title":"Switching from insulin injections to degludec/liraglutide in older frail persons: 6-month body composition remodelling.","authors":"Mancinetti, Francesca; Xenos, Dionysios; De Fano, Michelantonio; Mazzieri, Alessio; Ercolani, Sara; Mecocci, Patrizia; Porcellati, Francesca; Boccardi, Virginia","year":2025,"journal":"European geriatric medicine","doi":"10.1007/s41999-025-01271-3","pmid":"40624450","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 36 frail insulin-treated older adults (mean age 79.6) switched to IDegLira for 6 months:\n\nInsulin reduction:\n- Total insulin dropped from 34.52 to 24.30 U/day\n- Bolus insulin nearly discontinued\n- IDegLira titrated from 15.66 to 22.41 units/day\n\nBody composition improvements (adjusted for covariates):\n- Fat-free mass: +3.17 kg/m\n- Body cell mass: +7.82 kg/m\n- Phase angle: +1.75° (cellular health marker)\n- Basal metabolic rate: +217.6 kcal\n- Fat mass: decreased significantly (P < 0.001)\n\nMetabolic improvements:\n- HbA1c: 7.29% → 7.05% (P = 0.089, favorable trend)\n- Insulin resistance (METS-IR): 42.39 → 32.84 (P < 0.0001)","whyItMatters":"Frailty in the elderly is characterized by muscle loss (sarcopenia), and traditional insulin therapy can worsen this by promoting fat gain and reducing muscle mass. This study shows that adding liraglutide (via the IDegLira combination) reverses this pattern — patients gained muscle and lost fat. For the growing population of frail elderly diabetic patients, this represents a potentially transformative change in treatment approach. The simpler once-daily injection also reduces treatment burden for patients who may struggle with complex insulin regimens.","specificNumbers":"","methodology":"Retrospective analysis of 36 frail insulin-treated older adults (18 women, 18 men, mean age 79.6 years) from the STOP (Simplifying Treatment in Older People) study. Patients were switched from existing insulin regimens to once-daily IDegLira. Body composition was measured by bioelectrical impedance analysis (BIA) at baseline and 6 months. Changes were evaluated using adjusted mixed models for repeated measures controlling for multiple covariates. Glycemic control (HbA1c) and insulin resistance (METS-IR index) were also tracked.","limitations":"Retrospective design without a control group limits causal conclusions. Small sample (36 patients) at a single center. Bioelectrical impedance analysis (BIA) is less precise than DXA or MRI for body composition. The body composition improvements could partially reflect reduced fluid retention from lower insulin doses rather than true muscle gain. Only 6-month follow-up — longer-term effects are unknown. The HbA1c change was not statistically significant (P = 0.089)."},{"rthcId":"RPEP-12429","title":"Comparing the performance of electrostatic repulsion-reversed phase chromatography approaches in the resolution of complex peptide mixture: Liraglutide as case study.","authors":"Manetto, Simone; Mazzoccanti, Giulia; Bassan, Michele; Macis, Marco; Cabri, Walter; Ciogli, Alessia; Ricci, Antonio; Gasparrini, Francesco","year":2025,"journal":"European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 211, 107120","doi":"10.1016/j.ejps.2025.107120","pmid":"40339761","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12430","title":"Activation of δ-opioid receptors blocks allodynia in a model of headache induced by PACAP.","authors":"Mangutov, Elizaveta; Dripps, Isaac; Siegersma, Kendra; Zhang, Yanping; Bocian, Rebecca; Asif, Sarah; Halbesma, Timothy; Witkowski, Wiktor; Pradhan, Amynah A","year":2025,"journal":"British journal of pharmacology, 182(7), 1630-1643","doi":"10.1111/bph.17424","pmid":"39797405","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12431","title":"Peptide-grafted nanogels for sustained endothelin and bradykinin blockade in osteoarthritis.","authors":"Manivong, Seng; Garcia-Ac, Araceli; Mahrouche, Louiza; Guerra, Fabiana; Séguy, Line; Sirois, Pierre; Banquy, Xavier; Roullin, Valérie Gaëlle; Moldovan, Florina","year":2025,"journal":"International journal of pharmaceutics, 683, 126089","doi":"10.1016/j.ijpharm.2025.126089","pmid":"40840814","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12432","title":"Electron Capture Dissociation for Discovery Top-Down Proteomics of Peptides and Small Proteins on Chromatographic Time Scales.","authors":"Manly, Lester S; Roberts, Anne M; Beckman, Joseph S; Roberts, Blaine R","year":2025,"journal":"Journal of the American Society for Mass Spectrometry, 36(10), 2079-2093","doi":"10.1021/jasms.5c00116","pmid":"40877745","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12433","title":"The Obesity Drug Revolution: New Frontiers in Pharmacotherapy.","authors":"Manoria, Prabhash C","year":2025,"journal":"Cureus, 17(11), e96713","doi":"10.7759/cureus.96713","pmid":"41393538","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12434","title":"PIONEER REAL Italy: Real-World Usage of Once-Daily Oral Semaglutide in Adults with Type 2 Diabetes.","authors":"Manti, Roberta; De Cosmo, Salvatore; Desenzani, Paolo; Ferrara, Lidia; Girelli, Angela; Memoli, Giuseppe; Bisio, Alessandro; Braae, Uffe Christian; Deinega, Alisa; Berra, Cesare","year":2025,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 16(5), 1019-1032","doi":"10.1007/s13300-025-01719-6","pmid":"40128506","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12435","title":"Glucagon-Like Peptide-1 Receptor Agonists Improve MASH and Liver Fibrosis: A Meta-Analysis of Randomised Controlled Trials.","authors":"Mantovani, Alessandro; Morandin, Riccardo; Fiorio, Veronica; Lando, Maria Giovanna; Stefan, Norbert; Tilg, Herbert; Byrne, Christopher D; Targher, Giovanni","year":2025,"journal":"Liver international : official journal of the International Association for the Study of the Liver, 45(9), e70256","doi":"10.1111/liv.70256","pmid":"40736113","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 13 phase 2/3 RCTs with 1,811 participants:\n\n- MASH resolution without worsening fibrosis (3 RCTs, biopsy-confirmed): OR 3.48 (95% CI: 2.69-4.51, I²=0%) — 3.5 times more likely with GLP-1RAs\n- Fibrosis improvement without worsening MASH: OR 1.79 (95% CI: 1.37-2.35, I²=0%) — 1.8 times more likely\n- Liver fat reduction by MRI (9 RCTs): -4.50% (95% CI: -6.60 to -2.40, I²=95.9%)\n- Semaglutide 2.4 mg/week was the most studied and effective agent\n- Critical exception: In 1 RCT of MASH-related compensated cirrhosis, semaglutide did NOT achieve MASH resolution or fibrosis improvement vs. placebo","whyItMatters":"This meta-analysis provides stronger evidence for GLP-1 drugs' liver benefits than previous analyses — critically, it shows fibrosis improvement (OR 1.79), which the earlier semaglutide-only meta-analysis did not find significant. The zero heterogeneity (I²=0%) for both histological outcomes increases confidence. However, the cirrhosis finding is sobering: once the liver has scarred irreversibly, GLP-1 drugs may be too late. This reinforces the importance of early intervention — using GLP-1 drugs before liver disease progresses to its most advanced stage.","specificNumbers":"","methodology":"Systematic search of three electronic databases through April 2025 identified 13 phase 2 or 3 RCTs examining GLP-1RAs in MASLD/MASH patients. MASLD/MASH was diagnosed by liver biopsy (4 trials) or MRI-based techniques (9 trials). Primary outcomes were MASH resolution without fibrosis worsening and fibrosis improvement without MASH worsening (biopsy-confirmed in relevant trials). Secondary outcome was MRI-measured liver fat reduction. Random-effects meta-analysis was used given the potential for between-study variability.","limitations":"The meta-analysis includes only 1,811 participants across 13 trials — relatively small for a meta-analysis. Only 4 trials used liver biopsy (the gold standard), while 9 used MRI. The liver fat reduction outcome showed very high heterogeneity (I²=95.9%), likely due to different MRI techniques and patient populations. The cirrhosis finding is based on a single RCT. Semaglutide 2.4 mg dominated the evidence base, so conclusions may not generalize equally to other GLP-1RAs. Long-term effects on liver-related clinical events (liver failure, transplant, death) were not assessed."},{"rthcId":"RPEP-12436","title":"Novel insights into the effects of JMV2894, a growth hormone secretagogue, in Duchenne muscular dystrophy: A preclinical study in the D2-mdx mouse model.","authors":"Mantuano, Paola; Boccanegra, Brigida; Marinelli, Manuel; Cristiano, Enrica; Lenti, Roberta; Tulimiero, Lisamaura; De Bellis, Michela; Fehrentz, Jean-Alain; Denoyelle, Séverine; Bresciani, Elena; Torsello, Antonio; Mele, Antonietta; Liantonio, Antonella; Cappellari, Ornella; De Luca, Annamaria","year":2025,"journal":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 193, 118767","doi":"10.1016/j.biopha.2025.118767","pmid":"41223758","tags":[],"studyType":"animal-study","evidenceStrength":"low-moderate","keyFinding":"JMV2894, a pseudopeptide growth hormone secretagogue, showed remarkable anti-atrophic effects in a severe mouse model of Duchenne muscular dystrophy (D2-mdx). At the lower dose (640 µg/kg), it significantly increased muscle fiber size and decreased expression of muscle-wasting genes (Atrogin and MuRF1).\n\nThe treatment partially improved hind limb muscle function, reduced muscle echo-density (a measure of tissue damage), and decreased expression of matrix-remodeling genes including MMP-9, ADAMTS-5, TGF-β1, and type I collagen. However, the anti-fibrotic effect was only mild histologically despite the gene expression changes.\n\nThe mechanism appears to be GH-mediated: JMV2894 increased IGF-1 gene expression and plasma levels, along with IGF-1 receptor and downstream signaling proteins. The treatment was well-tolerated at both doses over 6 weeks, though limited muscle drug exposure suggests improved formulations could enhance results.","whyItMatters":"Duchenne muscular dystrophy is a devastating genetic disease with no cure, causing progressive muscle wasting and early death. This study provides the first evidence that a growth hormone secretagogue peptide can combat muscle atrophy in a severe DMD mouse model through IGF-1 signaling. The anti-atrophic, anti-inflammatory, and anti-fibrotic properties of JMV2894 suggest growth hormone secretagogues could be a multi-target therapeutic approach for DMD.","specificNumbers":"Doses: 640 and 1280 µg/kg SC · 6 weeks treatment · 4-week-old D2-mdx mice · Increased myofiber size · Decreased Atrogin + MuRF1 expression · Increased IGF-1 plasma levels · Decreased MMP-9, ADAMTS-5, TGF-β1, collagen Iα1","methodology":"Four-week-old D2-mdx mice (a severe DMD model with hyper-fibrotic and atrophic phenotype) received subcutaneous JMV2894 at 640 or 1280 µg/kg for six weeks. Researchers measured hind limb muscle function (plantar flexor torque), muscle volume (ultrasound), echo-density, muscle fiber size (histology), fibrosis, gene expression of matrix-remodeling and atrophy markers, and IGF-1 levels in plasma and tissue.","limitations":"This is a preclinical mouse study — results may not translate to human DMD patients. The D2-mdx model, while severe, doesn't fully replicate human disease. The anti-fibrotic effect was mild despite gene expression changes, and limited drug exposure to muscle tissue suggests formulation improvements are needed. The lower dose was surprisingly more effective for some outcomes, which is not fully explained."},{"rthcId":"RPEP-12437","title":"Antioxidant, Hypotensive, and Antidiabetic Breakthroughs: Bromelain Hydrolysis Unlocks Quinoa's Peptide Potential - In Silico and In Vitro Approach.","authors":"Manzanilla-Valdez, Maria Lilibeth; Montaño, Sarita; Martinez-Villaluenga, Cristina; Zúñiga, Fernanda; Boesch, Christine; Hernandez-Alvarez, Alan Javier","year":2025,"journal":"Journal of agricultural and food chemistry, 73(36), 22877-22894","doi":"10.1021/acs.jafc.5c03789","pmid":"40854188","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12438","title":"Psychocardiological impact of depression on medication adherence, ventricular function, and readmission in heart failure: A retrospective cohort study.","authors":"Mao, Fu-Gang; Tang, Ya-Ling; Wang, Xiao-Yuan; Jin, Xing; Fan, Jing-Yuan","year":2025,"journal":"World journal of psychiatry, 15(12), 109437","doi":"10.5498/wjp.v15.i12.109437","pmid":"41357921","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12439","title":"Association between glucagon-like peptidase 1 receptor agonist and obesity-related cancer in overweight or obese patients with type 2 diabetes: a nationwide cohort study.","authors":"Mao, Xianhua; Zhang, Xinrong; Henry, Linda; Cheung, Ka Shing; Yuen, Man-Fung; Cheung, Ramsey; Seto, Wai-Kay; Nguyen, Mindie H","year":2025,"journal":"Journal of the National Cancer Institute, 117(10), 2053-2061","doi":"10.1093/jnci/djaf163","pmid":"40632592","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 agonist users had a significantly lower incidence of obesity-related cancer at 7.5 per 1,000 person-years versus 8.1 for other glucose-lowering drugs, translating to an adjusted hazard ratio of 0.87 (95% CI: 0.83–0.91). The association was consistent across all comparator drugs: HR 0.90 vs metformin, 0.88 vs DPP-4 inhibitors, 0.84 vs thiazolidinediones, 0.81 vs sulfonylureas, 0.73 vs SGLT2 inhibitors, and 0.70 vs insulin.\n\nThe risk reduction showed a dose-response relationship with body weight: overweight patients had an HR of 0.95 (not statistically significant), mild-to-moderate obesity had HR 0.90, and severe obesity had HR 0.82 (interaction P = 0.032). This suggests the cancer-protective association strengthens as obesity severity increases.","whyItMatters":"Obesity is a known risk factor for at least 13 types of cancer, and people with type 2 diabetes already face elevated cancer risk. If GLP-1 drugs — originally designed for blood sugar and weight management — also reduce cancer risk, it would represent a major additional benefit for the millions of people now taking these medications. This is one of the largest studies to date examining this association.","specificNumbers":"","methodology":"This was a retrospective nationwide cohort study using Merative MarketScan research databases covering US commercial and Medicare claims data. Researchers identified all overweight or obese adults aged 20–79 with type 2 diabetes who started GLP-1 agonists or other glucose-lowering drugs between January 2016 and June 2021. The primary outcome was diagnosis of any of 13 obesity-related cancer types. Analyses used adjusted hazard ratios controlling for confounders, with over 2 million person-years of follow-up.","limitations":"This is an observational cohort study using insurance claims data, so it cannot prove that GLP-1 drugs directly cause cancer risk reduction — only that an association exists. Claims databases may have coding inaccuracies and cannot capture important confounders like diet, exercise, smoking, or family cancer history. The study period (2016–2021) predates widespread use of newer GLP-1 drugs like high-dose semaglutide. Follow-up time may be too short to capture cancers with long latency periods."},{"rthcId":"RPEP-12440","title":"Glucagon-like peptide 1 receptor agonist and reduced liver and non-liver complications in adults with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease: a target trial emulation study.","authors":"Mao, Xianhua; Zhang, Xinrong; Lai, Rongtao; Cheung, Ka-Shing; Yuen, Man-Fung; Cheung, Ramsey; Seto, Wai-Kay; Nguyen, Mindie H","year":2025,"journal":"Clinical and molecular hepatology, 31(3), 1084-1099","doi":"10.3350/cmh.2024.1096","pmid":"40268291","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12441","title":"Real-world Evidence on Oral Semaglutide for the Management of Type 2 Diabetes. A Narrative Review for Clinical Practice.","authors":"Marassi, M; Fadini, G P","year":2025,"journal":"Clinical therapeutics, 47(1), 102-110","doi":"10.1016/j.clinthera.2024.11.005","pmid":"39616020","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12442","title":"A Comprehensive Overview of Antimicrobial Peptides: Broad-Spectrum Activity, Computational Approaches, and Applications.","authors":"Marciano, Camila Langer; Félix de Lima, João Vítor; Couto Rosa, Murilo Sousa do; do Nascimento, Rafaelly Avelar; Ferraz, Antonio de Oliveira; Silva, Iago Castro da; Chrysostomo-Massaro, Taís Nader; Rosa-Garzon, Nathália Gonsales da; Cabral, Hamilton","year":2025,"journal":"Antibiotics (Basel, Switzerland), 14(11)","doi":"10.3390/antibiotics14111115","pmid":"41301610","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12443","title":"Tirzepatide attenuates estrogen deficiency-induced metabolic dysfunction-associated steatotic liver disease progression by reducing steatosis, inflammation, and fibrosis in obese-diabetic mice.","authors":"Marcondes-de-Castro, Ilitch Aquino; Marinho, Thatiany Souza; Aguila, Marcia Barbosa; Mandarim-de-Lacerda, Carlos Alberto","year":2025,"journal":"Menopause (New York, N.Y.)","doi":"10.1097/GME.0000000000002683","pmid":"41217893","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12444","title":"Proteomic changes upon treatment with semaglutide in individuals with obesity.","authors":"Maretty, Lasse; Gill, Dipender; Simonsen, Lotte; Soh, Keng; Zagkos, Loukas; Galanakis, Michael; Sibbesen, Jonas; Iglesias, Miquel Triana; Secher, Anna; Valkenborg, Dirk; Purnell, Jonathan Q; Knudsen, Lotte Bjerre; Tahrani, Abd A; Geybels, Milan","year":2025,"journal":"Nature medicine, 31(1), 267-277","doi":"10.1038/s41591-024-03355-2","pmid":"39753963","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12445","title":"Tirzepatide Treatment and Associated Changes in β-Cell Function and Insulin Sensitivity in People With Obesity or Overweight With Prediabetes or Normoglycemia: A Post Hoc Analysis From the SURMOUNT-1 Trial.","authors":"Mari, Andrea; Stefanski, Adam; van Raalte, Daniel H; Ma, Xiaosu; LaBell, Elizabeth S; Fan, Ludi; Lee, Clare J; Thomas, Melissa K; Bunck, Mathijs C; Ferrannini, Ele","year":2025,"journal":"Diabetes care, 48(9), 1622-1627","doi":"10.2337/dc25-0763","pmid":"40694530","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12446","title":"Computational assessment of the dimeric incretin GLP-1cpGLP-1 reveals the structural bases for its activity.","authors":"Mariam, Zamara; Abolhasan, Mohammad Reza; Reynolds, Christopher A; Yousefi, Reza; Deganutti, Giuseppe","year":2025,"journal":"Biochemical and biophysical research communications, 781, 152525","doi":"10.1016/j.bbrc.2025.152525","pmid":"40865282","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12447","title":"Neurobeachin (NBEA) is a novel gene associated with GLP-1 receptor agonist associated weight loss.","authors":"Mariam-Smith, Arshiya; Breeyear, Joseph H; Daniels, Noah J; Pantalone, Kevin M; Griebeler, Marcio L; Motsinger-Reif, Alison A; Rotroff, Daniel M","year":2025,"journal":"Diabetes, obesity & metabolism, 27(10), 5632-5642","doi":"10.1111/dom.16612","pmid":"40677145","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Individuals meeting the responsive NBEA genetic score threshold were 82% more likely to be highly responsive (top 20th percentile for weight loss) on liraglutide (FDR p = 1.8 × 10⁻⁶), validated in the UK Biobank (OR = 2.37, p = .008). For semaglutide, the responsive threshold showed OR = 1.63 in discovery and OR = 2.21 in validation. For non-responsiveness on liraglutide, the NBEA score predicted those with no weight loss (OR significant in both cohorts, p < .041), though the non-response score did not validate for semaglutide.","whyItMatters":"With GLP-1 receptor agonists costing thousands of dollars annually and not working equally for everyone, being able to predict who will respond best could save patients time, money, and frustration — and help healthcare systems allocate these medications more effectively through personalized prescribing.","specificNumbers":"","methodology":"The study used real-world data from the NIH All of Us cohort (N = 6,556) to develop a NBEA genetic score for weight loss at 12–18 months on GLP-1RAs, then independently validated it in the UK Biobank (N = 241). Logistic regression modeled associations between the genetic score and weight loss outcomes including high responsiveness and non-responsiveness.","limitations":"The validation cohort (UK Biobank, N = 241) was relatively small compared to the discovery cohort. The non-response NBEA score did not validate for semaglutide, suggesting drug-specific genetic effects. The study used real-world data rather than controlled trial data, which may introduce confounders. Only 12–18 month outcomes were assessed."},{"rthcId":"RPEP-12448","title":"Principal components analysis on genes related to inflammasome complex and microglial activation in the hypothalamus of obese mice treated with semaglutide (GLP-1 analog).","authors":"Marinho, Thatiany S; Fabiano, Matheus M; Aguila, Marcia B; Mandarim-de-Lacerda, Carlos A","year":2025,"journal":"Brain research, 1846, 149225","doi":"10.1016/j.brainres.2024.149225","pmid":"39243951","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide reduced weight gain and food efficiency in high-fat-fed mice. It lowered plasma TNF-α, MCP1, and resistin. In the hypothalamus, semaglutide suppressed pro-inflammatory genes (Tlr4, Mcp1, Il6, Tnfa), inflammasome complex genes (Nlrp3, Caspase 1, Il1b, Il18), and microglial activation markers (Iba1, Cd68, Arg1). Principal components analysis revealed that pair-fed mice (same weight loss, no drug) clustered with untreated obese mice — not with semaglutide-treated mice — demonstrating that the neuroinflammatory benefits are drug-specific and weight-loss-independent.","whyItMatters":"There's growing interest in semaglutide's potential benefits beyond weight loss and blood sugar control — including neuroprotection and cognitive health. This study provides direct evidence that semaglutide reduces brain inflammation through a mechanism independent of weight loss. Since hypothalamic inflammation drives continued obesity and metabolic dysfunction, this anti-inflammatory effect may be part of why GLP-1 drugs work so well — and hints at potential applications for neurodegenerative diseases.","specificNumbers":"","methodology":"Male C57BL/6J mice were fed control or high-fat diets for 16 weeks, then divided into 6 groups for a 4-week treatment phase: control, control+semaglutide, control pair-fed, high-fat, high-fat+semaglutide, and high-fat pair-fed. Weight gain, food efficiency, plasma biochemistry, and hypothalamic gene expression were measured. Principal components analysis was used to distinguish drug effects from weight loss effects.","limitations":"This is a mouse study using diet-induced obesity, which may not fully model human obesity or neuroinflammation. The 4-week treatment period is short. Only male mice were studied, so sex-specific effects cannot be assessed. Gene expression was measured but protein levels and functional neurological outcomes were not. The hypothalamus was analyzed as a whole, without distinguishing between specific nuclei or cell types beyond microglial markers."},{"rthcId":"RPEP-12449","title":"Hypersensitivity to liraglutide: A case report.","authors":"Marino-Fernández, Ana G; García-Gutiérrez, Irene; Alonso Juaristi, Sofía; López Gutiérrez, Jaime; Tawfiq Piedad, Mariam; Guerrero Sotelo, Ángel L; Albarracín Contreras, Ángel J; Ortiz Aljaro, Pilar; Rodríguez Fernández, Fernando","year":2025,"journal":"Asia Pacific allergy, 15(2), 115-117","doi":"10.5415/apallergy.0000000000000149","pmid":"40718123","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12450","title":"Body image and interest in GLP-1 weight loss medications.","authors":"Markey, Charlotte H; August, Kristin J; Malik, Dua; Richeson, Alexis","year":2025,"journal":"Body image, 53, 101890","doi":"10.1016/j.bodyim.2025.101890","pmid":"40267815","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12451","title":"LightCPPgen: An explainable machine learning pipeline for rational design of cell penetrating peptides.","authors":"Maroni, Gabriele; Stojceski, Filip; Pallante, Lorenzo; Deriu, Marco A; Piga, Dario; Grasso, Gianvito","year":2025,"journal":"International journal of antimicrobial agents, 66(6), 107611","doi":"10.1016/j.ijantimicag.2025.107611","pmid":"40930190","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The LightCPPgen pipeline integrates a LightGBM machine learning model (using 20 explainable physicochemical features) with a genetic algorithm to systematically design cell-penetrating peptide sequences. The system can take a non-penetrating peptide and optimize it for cell entry while maximizing similarity to the original sequence — preserving its intended biological function. The approach prioritizes explainability, allowing researchers to understand which molecular features drive cell penetration, rather than relying on opaque deep learning models.","whyItMatters":"Cell-penetrating peptides are one of the most promising tools for delivering drugs, genes, and diagnostic agents into cells, but designing new ones has been slow and expensive. LightCPPgen offers a way to computationally design optimized CPPs before going to the lab, potentially saving months of trial-and-error experimentation. The focus on explainability means researchers don't just get peptide candidates — they learn what molecular properties make them work, advancing fundamental understanding of cell penetration.","specificNumbers":"","methodology":"Researchers developed a LightGBM-based predictive model trained on known CPP and non-CPP sequences, using 20 physicochemical features selected for interpretability. They coupled this predictor with a genetic algorithm (GA) optimization engine that iteratively modifies peptide sequences to maximize predicted cell penetration while maintaining similarity to the starting sequence. The GA was tuned for computational efficiency. The pipeline outputs ranked candidate sequences for experimental validation.","limitations":"The abstract does not describe experimental validation of computationally designed peptides — the pipeline generates candidates but their actual cell-penetrating ability would need to be confirmed in the lab. The model is based on known CPP datasets, which may not capture all the diversity of cell-penetrating mechanisms. Predictions of cell penetration in silico may not account for cell-type specific differences, membrane composition variability, or in vivo conditions."},{"rthcId":"RPEP-12452","title":"Effects of Glucagon-Like Peptide 1 Receptor Agonist Initiation in Patients With Heart Failure With Reduced Ejection Fraction and Implantable Cardiac Devices.","authors":"Marques, Pedro; Travlos, Christoforos K; Matias, Paula; Neves, João Sérgio; Tsoukas, Michael A; Mavrakanas, Thomas A; Joza, Jacqueline; Ferreira, João Pedro; Sharma, Abhinav","year":2025,"journal":"JACC. Heart failure, 13(11), 102573","doi":"10.1016/j.jchf.2025.102573","pmid":"40992090","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12453","title":"GLP-1 Analogues in the Neurobiology of Addiction: Translational Insights and Therapeutic Perspectives.","authors":"Marquez-Meneses, Juan David; Olaya-Bonilla, Santiago Arturo; Barrera-Carreño, Samuel; Tibaduiza-Arévalo, Lucía Catalina; Forero-Cárdenas, Sara; Carrillo-Vaca, Liliana; Rojas-Rodríguez, Luis Carlos; Calderon-Ospina, Carlos Alberto; Rodríguez-Quintana, Jesús","year":2025,"journal":"International journal of molecular sciences, 26(11)","doi":"10.3390/ijms26115338","pmid":"40508146","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12454","title":"Dual-Peptide PAMAM Dendrimer Conjugates for Enhanced Cell Uptake via E-Selectin Targeting.","authors":"Marrugo, Kelly P; Manzo-Merino, Joaquín; Jiménez, Verónica A; Campos, Cristian H; Alderete, Joel B","year":2025,"journal":"Bioconjugate chemistry, 36(12), 2608-2617","doi":"10.1021/acs.bioconjchem.5c00443","pmid":"41269873","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12455","title":"Late response to anti-CGRP therapy for migraine.","authors":"Marsico, Oreste; Lioi, Marta; Trimboli, Michele","year":2025,"journal":"Pain management, 15(10), 745-751","doi":"10.1080/17581869.2025.2550931","pmid":"40839420","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12456","title":"Unmasking the relationship between CGRP and glutamate: from peripheral excitation to central sensitization in migraine.","authors":"Martami, Fahimeh; Holton, Kathleen F","year":2025,"journal":"The journal of headache and pain, 26(1), 101","doi":"10.1186/s10194-025-02043-x","pmid":"40329208","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review synthesizes evidence that glutamate acts as an upstream trigger for CGRP release in the trigeminovascular system. Elevated glutamate levels contribute to both peripheral sensitization (nerve activation around blood vessels) and central sensitization (amplified pain processing in the brain), potentially driving the transition from episodic to chronic migraine. The CGRP-glutamate relationship is bidirectional, with CGRP also capable of enhancing glutamate signaling, creating a feedforward loop that perpetuates migraine.","whyItMatters":"About one-third of migraine patients don't respond to CGRP-targeting therapies — the most important advance in migraine treatment in decades. Understanding that glutamate may be the upstream driver of CGRP release explains why blocking CGRP alone isn't always sufficient. This points to glutamate-targeting strategies as a complementary or alternative approach, potentially expanding effective treatment options for treatment-resistant migraine patients.","specificNumbers":"","methodology":"This is a narrative review examining the scientific literature on CGRP and glutamate interactions in migraine pathophysiology, covering evidence from preclinical studies, neuroimaging, and clinical observations. The review integrates findings on peripheral excitation, central sensitization, and therapeutic implications.","limitations":"As a narrative review, this does not include systematic methodology or meta-analysis. The glutamate-CGRP interaction model is largely based on preclinical data and has not been fully validated in clinical trials targeting glutamate for migraine. The complexity of glutamate signaling (essential for normal brain function) makes targeting it therapeutically challenging without side effects."},{"rthcId":"RPEP-12457","title":"Tirzepatide on ingestive behavior in adults with overweight or obesity: a randomized 6-week phase 1 trial.","authors":"Martin, Corby K; Carmichael, Owen T; Carnell, Susan; Considine, Robert V; Kareken, David A; Dydak, Ulrike; Mattes, Richard D; Scott, David; Shcherbinin, Sergey; Nishiyama, Hiroshi; Knights, Alastair; Urva, Shweta; Biernat, Lukasz; Pratt, Edward; Haupt, Axel; Mintun, Mark; Otero Svaldi, Diana; Milicevic, Zvonko; Coskun, Tamer","year":2025,"journal":"Nature medicine, 31(9), 3141-3150","doi":"10.1038/s41591-025-03774-9","pmid":"40555748","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12458","title":"Effects of environmental toxicant exposures on oxytocin and vasopressin systems in the developing brain: factors imparting risk and resilience.","authors":"Martin, Elise M; Xue, Jason; Smith, Caroline J","year":2025,"journal":"Behavioural brain research, 494, 115723","doi":"10.1016/j.bbr.2025.115723","pmid":"40617300","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Perinatal exposure to four major categories of environmental toxicants — flame retardants, pesticides, plastics (including BPA and phthalates), and air pollution — all induce measurable changes to oxytocin (OT) and arginine vasopressin (AVP) systems in the developing brain. These changes affect the neuropeptides themselves as well as their central receptors (oxytocin receptor and vasopressin V1a receptor).\n\nTwo primary biological mechanisms were identified: endocrine disruption (toxicants mimicking or blocking hormones) and maternal immune activation (toxicant-triggered inflammation in the mother affecting fetal brain development). Key resilience factors include positive psychosocial experiences for mothers, sex-dependent differences in vulnerability, a healthy gut microbiome, and the timing and dose of exposure. The gut microbiome emerged as a particularly promising target for intervention.","whyItMatters":"Environmental toxicants are everywhere — in furniture, food packaging, pesticides, and the air we breathe. This review shows these common exposures can fundamentally alter the brain's social bonding and stress regulation systems during the most vulnerable developmental period. Understanding these effects is critical for public health policy, especially since the review identifies modifiable factors (maternal stress, microbiome health) that could protect children even in the presence of unavoidable toxicant exposure.","specificNumbers":"","methodology":"This is a comprehensive narrative review synthesizing evidence from animal and human studies on environmental toxicant effects on the oxytocin and vasopressin neuropeptide systems. The authors reviewed literature on four major toxicant categories and examined both the molecular changes to OT/AVP systems and the behavioral outcomes. They also analyzed the mechanistic pathways and identified factors that modify susceptibility.","limitations":"As a review article, this paper synthesizes existing evidence rather than presenting new data. Much of the underlying research comes from animal models, which may not perfectly translate to human neurodevelopment. The complexity of real-world toxicant exposures (multiple simultaneous exposures at varying doses) is difficult to replicate in controlled studies. The review does not quantify effect sizes across studies or perform meta-analysis."},{"rthcId":"RPEP-12459","title":"Liraglutide as a treatment option for weight regain after laparoscopic sleeve gastrectomy in patients with obesity and higher anaesthesiologist risk.","authors":"Martines, Gennaro; Tomasicchio, Giovanni; Rotelli, Maria Teresa; De Fazio, Michele","year":2025,"journal":"Frontiers in surgery, 12, 1624455","doi":"10.3389/fsurg.2025.1624455","pmid":"41079295","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12460","title":"Possible Anti-Pain Vaccines: A Narrative Review of Emerging Strategies and Clinical Prospects.","authors":"Martins, Yuri Chaves; De-Sousa, Luciana Pereira; Murin, Peyton J; Sadeghipour, Hamed; Daniel-Ribeiro, Cláudio Tadeu","year":2025,"journal":"Vaccines, 13(9)","doi":"10.3390/vaccines13090909","pmid":"41012116","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12461","title":"Cannabinoid effective targeting of atherosclerotic plaquesin vivoby optimized-PLGA nanoparticles.","authors":"Martín-Navarro, L; Herrera, M D; Álvarez-Fuentes, J; Claro-Cala, Carmen; Martín-Banderas, L","year":2025,"journal":"Colloids and surfaces. B, Biointerfaces, 256(Pt 2), 115057","doi":"10.1016/j.colsurfb.2025.115057","pmid":"40858005","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12462","title":"Diabetes Mellitus and Chronic Kidney Disease: The Future Is Being Surpassed.","authors":"Martínez-Castelao, Alberto; Górriz, José Luis; Fernández-Fernández, Beatriz; Soler, María José; Navarro-González, Juan F","year":2025,"journal":"Journal of clinical medicine, 14(23)","doi":"10.3390/jcm14238326","pmid":"41375628","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12463","title":"Bifurcated projections from the trigeminal ganglion cells to the transverse sinus and infraorbital nerve in the rat: correlation with the oxytocin receptor and CGRP.","authors":"Martínez-Lorenzana, Guadalupe; Córdova-Quiroga, Aketzalli; Condés-Lara, Miguel; González-Hernández, Abimael","year":2025,"journal":"The journal of headache and pain, 26(1), 212","doi":"10.1186/s10194-025-02186-x","pmid":"41083933","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Retrograde tracing in rats confirmed that some trigeminal ganglion (TG) cells send bifurcated projections through both V1 (meningeal/ophthalmic) and V2 (infraorbital/facial) branches. Triple-labeling showed some of these dual-projecting cells expressed both CGRP and oxytocin receptors (OTR). At the meningeal level, OTR was expressed perivascularly and on CGRPergic nerve fibers, suggesting oxytocin could modulate CGRP release at the meningeal vasculature — a key site of migraine pain generation.","whyItMatters":"Understanding that single nerve cells can relay pain signals from both the brain's covering and the face explains why migraine involves both headache and facial pain/sensitivity. The co-expression of CGRP and oxytocin receptors on these cells suggests oxytocin-based therapies could target the same neurons that CGRP drugs target — potentially offering an additional or complementary approach to migraine treatment.","specificNumbers":"","methodology":"Male Wistar rats received retrograde neural tracers: True-blue (TB) into the V1 meningeal branch and Fluoro-Gold (FG) into the V2 infraorbital nerve. Immunofluorescence assays identified TG cells triple-labeled with CGRP/FG/TB and OTR/FG/TB. Additional immunofluorescence characterized OTR expression in meningeal vasculature and its relationship to CGRP fibers.","limitations":"The study was conducted in rats, and the trigeminal anatomy may differ in humans. The functional significance of the bifurcated projections and OTR expression was not tested — the study is purely anatomical/descriptive. Whether oxytocin actually modulates CGRP release at the meningeal vasculature in vivo was not demonstrated. Only male rats were used, despite migraine being more common in females."},{"rthcId":"RPEP-12464","title":"Chronic treatment with carboplatin induces mechanical hypersensitivity and neurochemical changes in the mouse dorsal root ganglia and spinal cord.","authors":"Martínez-Martínez, Arisai; Ponce-Gomez, Lizeth Yazmin; Vazquez-Mora, Juan Antonio; Ramírez-Quintanilla, Laura Yanneth; Torres-Rodríguez, Héctor Fabián; Peters, Christopher M; Jiménez-Andrade, Juan Miguel","year":2025,"journal":"Cancer chemotherapy and pharmacology, 95(1), 90","doi":"10.1007/s00280-025-04815-3","pmid":"40986117","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12465","title":"Oral Semaglutide and Cardiovascular Outcomes in People With Type 2 Diabetes, According to SGLT2i Use: Prespecified Analyses of the SOUL Randomized Trial.","authors":"Marx, Nikolaus; Deanfield, John E; Mann, Johannes F E; Arechavaleta, Rosario; Bain, Stephen C; Bajaj, Harpreet S; Bayer Tanggaard, Katrine; Birkenfeld, Andreas L; Buse, John B; Davicevic-Elez, Zaklina; Desouza, Cyrus; Emerson, Scott S; Engelmann, Mads D M; Hovingh, G Kees; Inzucchi, Silvio E; Jhund, Pardeep S; Mulvagh, Sharon L; Pop-Busui, Rodica; Poulter, Neil R; Rasmussen, Søren; Tu, Shih-Te; McGuire, Darren K","year":2025,"journal":"Circulation, 151(23), 1639-1650","doi":"10.1161/CIRCULATIONAHA.125.074545","pmid":"40156843","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12466","title":"Analysis of In Silico Properties and In Vitro Immunomodulatory Effects of Seven Synthetic Host Defence Peptides in Gilthead Seabream (Sparus aurata) Leucocytes.","authors":"Marín-Parra, Claudia; Serna-Duque, Jhon Alberto; Espinosa-Ruiz, Cristóbal; Esteban, María Ángeles","year":2025,"journal":"Marine biotechnology (New York, N.Y.), 27(4), 109","doi":"10.1007/s10126-025-10488-z","pmid":"40650808","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12467","title":"Piscidin 1 and 2 of gilthead seabream (Sparus aurata): new insights into their role as host defense peptides.","authors":"Marín-Parra, Claudia; Serna-Duque, Jhon Alberto; Espinosa-Ruiz, Cristóbal; Albadalejo-Riad, Nora; Bardera, Guillermo; Thompson, Kim; Esteban, María Ángeles","year":2025,"journal":"Fish & shellfish immunology, 165, 110501","doi":"10.1016/j.fsi.2025.110501","pmid":"40518032","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12468","title":"Effectiveness of anti-CGRP monoclonal antibodies and onabotulinumtoxinA in menstrually-related migraine: The unmet need of perimenstrual headache days.","authors":"Mas-de-Les-Valls, Rut; Gómez-Dabó, Laura; Caronna, Edoardo; Gallardo, Victor J; Alpuente, Alicia; Torres-Ferrus, Marta; Pozo-Rosich, Patricia","year":2025,"journal":"Cephalalgia : an international journal of headache, 45(4), 3331024251332519","doi":"10.1177/03331024251332519","pmid":"40239029","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12469","title":"Novel Insights into Salt-Sensitivity of Blood Pressure in African Adults with and without HIV: Comprehensive Inflammatory, renal and Cardiometabolic Profiling in a Zambian Cohort.","authors":"Masenga, Sepiso K; Povia, Joreen P; Graham, Catherine Anna-Marie; Mavrommatis, Yiannis; Hamooya, Benson M; Pilic, Leta; Kirabo, Annet","year":2025,"journal":"medRxiv : the preprint server for health sciences","doi":"10.1101/2025.11.17.25340449","pmid":"41332828","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12470","title":"Evaluation of physicochemical, textural, and microbial characteristics of probiotic soy cheese during storage: Generation and isolation of bioactive peptides.","authors":"Mashayekh, Somayeh; Pourahmad, Rezvan; Akbari-Adergani, Behrouz; Eshaghi, Mohammad Reza","year":2025,"journal":"Food science and technology international = Ciencia y tecnologia de los alimentos internacional, 31(6), 516-528","doi":"10.1177/10820132231226257","pmid":"38193167","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12471","title":"RISING STARS: Effects of a GLP-1 receptor polymorphism on responses to liraglutide.","authors":"Mashayekhi, Mona; Safa, Bilgunay Ilkin; Nian, Hui; Devin, Jessica K; Gamboa, Jorge L; Yu, Chang; Chen, Rui; Beckman, Joshua A; Koethe, John R; Silver, Heidi J; Niswender, Kevin; Luther, James M; Brown, Nancy J","year":2025,"journal":"The Journal of endocrinology, 267(1)","doi":"10.1530/JOE-25-0174","pmid":"41042549","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12472","title":"Impact of glucagon-like peptide-1 receptor agonists on postoperative complications after total joint arthroplasty: A systematic review and meta-analysis.","authors":"Mashayekhi, Yashar; Asgari, Amir-Mohammad; Pahlevan-Fallahy, Mohammad-Taha; Karimi, Mohammad Amin; Jalali, Ronak; Shaker, Farhad","year":2025,"journal":"Journal of orthopaedic surgery (Hong Kong), 33(3), 10225536251391959","doi":"10.1177/10225536251391959","pmid":"41233973","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12473","title":"Next-generation antiviral peptides: AI-driven design, translational delivery platforms, and future therapeutic directions.","authors":"Mashhadi Abolghasem Shirazi, Maryam; Haghighat, Setareh; Nikbakht, Zahra; Salimkia, Elaheh; Kiumarsy, Armity","year":2025,"journal":"Virus research, 361, 199642","doi":"10.1016/j.virusres.2025.199642","pmid":"41106780","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12474","title":"Sleeve Gastrectomy Versus Semaglutide for Weight Loss in a Severely Obese Minority Cohort: A Propensity-Matched Study.","authors":"Masrur, Mario A; Manueli Laos, Emiliano G; Zhang, Lily; Acosta, Andres; Pirzada, Amber; Schlottmann, Francisco","year":2025,"journal":"Obesity surgery, 35(3), 852-859","doi":"10.1007/s11695-025-07712-z","pmid":"39875789","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12475","title":"The Salmonella phage shock protein system is required for defense against host antimicrobial peptides.","authors":"Massicotte, Marie-Ange; Fiebig, Aline A; Bogza, Andrei; Coombes, Brian K","year":2025,"journal":"PLoS pathogens, 21(9), e1013132","doi":"10.1371/journal.ppat.1013132","pmid":"40924764","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Temporal transcriptomics revealed that the phage shock protein (Psp) system is highly expressed in intracellular Salmonella Typhimurium with sustained expression throughout macrophage infection. The Psp system is regulated by the virulence-associated two-component system SsrA-SsrB, coordinating its expression with other immune evasion functions.\n\nFunctional assays demonstrated that the Psp system mediates resistance specifically to host antimicrobial peptides, including cathelicidin-related antimicrobial peptide (CRAMP). This resistance supports bacterial persistence in host tissues and survival within macrophages. The findings establish the Psp system as a new adaptive mechanism for evading host antimicrobial peptide defenses.","whyItMatters":"Antimicrobial peptides are a critical first line of defense against bacterial infection. Understanding how pathogens like Salmonella evade these defenses reveals potential drug targets. Disabling the Psp system could make Salmonella more vulnerable to the body's natural antimicrobial peptides, potentially leading to new therapeutic strategies that enhance, rather than replace, the immune system's own weapons.","specificNumbers":"","methodology":"Comprehensive temporal transcriptome analysis of Salmonella Typhimurium across four stages of primary macrophage infection. Researchers identified highly expressed gene systems, characterized the regulation of the Psp system by the SsrA-SsrB two-component system, and performed functional assays testing Psp system mutants against host antimicrobial peptides (including CRAMP). Bacterial persistence was assessed in host tissues and within macrophages using mouse infection models.","limitations":"The study was conducted primarily in mouse macrophages and mouse infection models, which may not fully replicate human Salmonella infection. The transcriptomic analysis captures gene expression but not necessarily protein levels or activity. The specific molecular mechanism by which the Psp system confers antimicrobial peptide resistance is not fully elucidated. The study focused on Salmonella Typhimurium; other Salmonella serovars may have different resistance mechanisms."},{"rthcId":"RPEP-12476","title":"Anti-inflammatory effects of tirzepatide: a systematic review and meta-analysis.","authors":"Masson, Walter; Lobo, Martín; Nogueira, Juan P; Barbagelata, Leandro; Touzas, Pedro; Frías, Juan P","year":2025,"journal":"Reviews in endocrine & metabolic disorders","doi":"10.1007/s11154-025-09991-4","pmid":"41032183","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Compared to placebo, tirzepatide reduced hsCRP by 32.9% (95% CI: -33.6 to -32.2; I²=15.3%) and IL-6 by 17.8% (95% CI: -24.3 to -11.3; I²=1.6%). The hsCRP reduction was significant at all doses: 15 mg (-32.9%), 10 mg (-33.9%), and 5 mg (-20.3%). IL-6 reductions were also significant at all doses: 5 mg (-18.8%), 10 mg (-17.9%), and 15 mg (-16.8%). Low heterogeneity (I² values mostly under 20%) suggests consistent effects across studies.","whyItMatters":"Chronic low-grade inflammation is a hallmark of obesity and type 2 diabetes, contributing to cardiovascular disease, fatty liver disease, and other complications. While tirzepatide's metabolic benefits are well established, demonstrating significant anti-inflammatory effects adds another dimension to its therapeutic value. If tirzepatide directly reduces inflammation — not just as a downstream effect of weight loss — it could benefit patients with inflammatory conditions beyond diabetes and obesity.","specificNumbers":"","methodology":"This systematic review and meta-analysis followed PRISMA guidelines. Researchers searched for studies (both randomized clinical trials and observational cohort studies) that reported percentage changes in hsCRP and IL-6 with tirzepatide use. Seven RCTs and one observational study were included, with six eligible for quantitative meta-analysis. A random-effects model was used to pool results across studies.","limitations":"The number of studies included was relatively small (eight total, six in the meta-analysis). The meta-analysis could not determine whether the anti-inflammatory effects are independent of weight loss or secondary to it. Treatment durations varied across studies, and longer-term inflammatory marker data are limited. The observational study included may introduce bias compared to the RCTs. Not all inflammatory markers were assessed — only hsCRP and IL-6 were analyzed."},{"rthcId":"RPEP-12477","title":"Increased vision impairment reports linked to semaglutide: analysis of FDA adverse event data.","authors":"Massy, Marine; Marti, Stefanie; Hammer, Helly; Hoepner, Robert","year":2025,"journal":"BMC medicine, 23(1), 203","doi":"10.1186/s12916-025-04031-z","pmid":"40189538","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide showed significantly elevated reporting of vision impairment compared to multiple drug classes in the FDA Adverse Event Reporting System (FAERS):\n\n- vs. other GLP-1 receptor agonists: reporting odds ratio (rOR) 1.95 (95% CI 1.75–2.17, p < 0.0001)\n- vs. DPP-4 inhibitors: rOR 2.46 (95% CI 2.12–2.86, p < 0.0001)\n- vs. SGLT2 inhibitors: rOR 3.89 (95% CI 3.35–4.51, p < 0.0001)\n- vs. metformin: rOR 2.23 (95% CI 1.90–2.62, p < 0.0001)\n- vs. phentermine: rOR 1.57 (95% CI 1.07–2.31, p = 0.026)\n- vs. orlistat: rOR 3.77 (95% CI 2.96–4.81, p < 0.0001)\n\nOnly topiramate had higher vision impairment reporting than semaglutide (rOR 0.30, p < 0.0001).","whyItMatters":"Semaglutide is one of the most widely prescribed medications globally, used by millions for type 2 diabetes and weight loss. If it carries an elevated risk of vision impairment, this has major public health implications. This signal from FDA adverse event data is an early warning that warrants rigorous clinical investigation, especially as the patient population using semaglutide continues to expand rapidly.","specificNumbers":"","methodology":"The researchers analyzed data from the FDA Adverse Event Reporting System (FAERS), a publicly available database of voluntary adverse event reports. They compared the frequency of vision impairment reports for semaglutide against other antidiabetic medications (other GLP-1 agonists, DPP-4 inhibitors, SGLT2 inhibitors, metformin) and weight loss medications (phentermine, orlistat, topiramate). The main outcome measure was the reporting odds ratio (rOR), which compares how often a side effect is reported for one drug versus another.","limitations":"FAERS data is based on voluntary reports, not systematic surveillance, so it's subject to reporting bias — popular drugs like semaglutide may receive disproportionate attention. The analysis cannot establish causation, only an association in reporting patterns. The study uses reporting odds ratios, not absolute risk rates, so the actual clinical risk of vision impairment cannot be determined. Confounding factors like underlying diabetes severity, which itself causes vision problems, were not controlled for."},{"rthcId":"RPEP-12478","title":"Semaglutide Adherence and Cardiovascular Diseases in Patients With Type 2 Diabetes: Evidence From Real-World Data in Japan.","authors":"Masudo, Chikako; Horii, Takeshi; Suzuki, Ririka; Mihara, Kiyoshi","year":2025,"journal":"Cureus, 17(3), e80511","doi":"10.7759/cureus.80511","pmid":"40225492","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12479","title":"GLP-1 and GIP agonists in diabetes and obesity and the rise of dyspepsia.","authors":"Masulli, Maria; Tack, Jan; Esposito, Giuseppe; Sarnelli, Giovanni","year":2025,"journal":"Internal and emergency medicine, 20(8), 2291-2294","doi":"10.1007/s11739-025-04117-9","pmid":"40975854","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12480","title":"Ion-Channel-Targeting Scorpion Recombinant Toxin as Novel Therapeutic Agent for Breast Cancer.","authors":"Mata de Los Rios, Natalia; Gastelum-Arellanez, Argel; Clement, Herlinda; Álvarez-Cruz, Karely; Romero-Terrazas, Diana; Alvarado-González, Carolina; Hinojos-Gallardo, Luis Carlos; Corzo, Gerardo; Espino-Solis, Gerardo Pável","year":2025,"journal":"Toxins, 17(4)","doi":"10.3390/toxins17040166","pmid":"40278664","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12481","title":"Stable Gastric Pentadecapeptide BPC 157 as Therapy After Surgical Detachment of the Quadriceps Muscle from Its Attachments for Muscle-to-Bone Reattachment in Rats.","authors":"Matek, Danijel; Matek, Irena; Staresinic, Eva; Japjec, Mladen; Bojanic, Ivan; Boban Blagaic, Alenka; Beketic Oreskovic, Lidija; Oreskovic, Ivana; Ziger, Tihomil; Novinscak, Tomislav; Krezic, Ivan; Strbe, Sanja; Drinkovic, Martin; Brkic, Filip; Popic, Jelena; Skrtic, Anita; Seiwerth, Sven; Staresinic, Mario; Sikiric, Predrag; Brizic, Ivica","year":2025,"journal":"Pharmaceutics, 17(1)","doi":"10.3390/pharmaceutics17010119","pmid":"39861766","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12482","title":"Greater improvement in insulin sensitivity per unit weight loss associated with tirzepatide versus semaglutide: An exploratory analysis.","authors":"Mather, Kieren J; Mari, Andrea; Weerakkody, Govinda; Heise, Tim; DeVries, J Hans; Urva, Shweta; Coskun, Tamer; Milicevic, Zvonko; Haupt, Axel; Thomas, Melissa K","year":2025,"journal":"Diabetes, obesity & metabolism, 27(3), 1507-1514","doi":"10.1111/dom.16159","pmid":"39762971","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12483","title":"Impact of functionality and grading on survival in pancreatic neuroendocrine tumor patients receiving peptide receptor radionuclide therapy.","authors":"Mathew, Annie; Kersting, David; Fendler, Wolfgang P; Braegelmann, Johanna; Fuhrer, Dagmar; Lahner, Harald","year":2025,"journal":"Frontiers in endocrinology, 16, 1526470","doi":"10.3389/fendo.2025.1526470","pmid":"40303635","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 166 patients with metastatic pancreatic neuroendocrine tumors, 100 received PRRT. Overall survival for the entire cohort was 79 months. Patients receiving 4 or more cycles of PRRT achieved a median overall survival of 87 months, while those receiving 5 or more cycles reached 100 months.\n\nTumor grade was a significant factor: patients with grade 1 or 2 tumors had a median survival of 97 months compared to 74.5 months for grade 3 tumors (p=0.0055). Bone metastases also predicted worse outcomes — patients with bone metastases who received PRRT survived a median of 74 months versus 89 months for those without (p=0.013). Whether the tumor was functioning or non-functioning did not significantly affect survival after PRRT.","whyItMatters":"PRRT is an established treatment for neuroendocrine tumors, but randomized trial data on its impact on overall survival has been lacking. This real-world study provides important evidence that extended PRRT courses are associated with longer survival, and identifies which patients — those with lower-grade tumors and no bone spread — benefit most. This information can help clinicians make better-informed treatment decisions.","specificNumbers":"","methodology":"The researchers conducted a retrospective analysis of 166 patients with histologically confirmed metastatic pancreatic neuroendocrine tumors. Of these, 100 received PRRT with a median of four cycles. Survival outcomes were analyzed by subgroups based on tumor grading, tumor functionality (hormone-secreting vs. non-secreting), and presence of bone metastases.","limitations":"This was a retrospective study from a single center, which limits the ability to draw causal conclusions. The survival benefit of more PRRT cycles may partly reflect selection bias — healthier patients are more likely to tolerate and complete more treatment cycles. There was no randomized control group, and 19% of PRRT patients discontinued due to disease progression, toxicity, or death. The study also did not detail specific PRRT regimens or radionuclides used."},{"rthcId":"RPEP-12484","title":"Superior growth performance in carp fry achieved with chitosan-alginate encapsulated A-ghrelin versus free peptide: Evidence from physiological, molecular, and morphological analyses.","authors":"Matinfar, Mohammad; Heidari, Behrooz; Valipour, AbdolMajid; Rahdari, Tahereh; Ramezanpour, Sorour; Hadavi, Mahvash; Asghari, S Mohsen","year":2025,"journal":"PloS one, 20(6), e0327235","doi":"10.1371/journal.pone.0327235","pmid":"40587525","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12485","title":"Facilitated identification of bioactive peptide fractions and optimization of enzymatic protein hydrolysis using size-exclusion chromatography fingerprints: Combining interval PLS and response surface modeling.","authors":"Matić, Josipa; Børilden, Ben; Sorokina, Liudmila; Rønning, Sissel Beate; Kristoffersen, Kenneth Aase; Afseth, Nils Kristian; Wubshet, Sileshi Gizachew","year":2025,"journal":"Talanta, 291, 127844","doi":"10.1016/j.talanta.2025.127844","pmid":"40048998","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12486","title":"Effects of Transcatheter Atrial Septal Defect Closure in Elderly Patients with Long-Standing Persistent Atrial Fibrillation.","authors":"Matsubara, Yuki; Yamano, Michiyo; Yamano, Tetsuhiro; Nakamura, Takeshi; Nakanishi, Naohiko; Zen, Kan; Shiraishi, Hirokazu; Matoba, Satoaki","year":2025,"journal":"International heart journal, 66(5), 805-812","doi":"10.1536/ihj.25-244","pmid":"41034026","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12487","title":"Atogepant for the preventive treatment of episodic migraine in Japanese participants: A phase 2/3, randomized, double-blind, placebo-controlled trial with an active treatment extension (RELEASE).","authors":"Matsumori, Yasuhiko; Yamada, Hiroshi; Nagaseki, Yoshishige; Shimizu, Kazutaka; Nagy, Krisztian; Matsuzawa, Ryotaro; Otani, Tetsuya; He, Molly Yizeng; Guo, Hua; Ahmadyar, Gina; Takeshima, Takao","year":2025,"journal":"Cephalalgia : an international journal of headache, 45(9), 3331024251374569","doi":"10.1177/03331024251374569","pmid":"41002192","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12488","title":"Exploring the association of natriuretic peptides with QTc interval in hemodialysis patients.","authors":"Matsumoto, Yoshihiro; Mori, Yasuo; Kageyama, Shinji; Yoshimura, Kazuaki; Saito, Takao; Terada, Risako; Nojima, Yohichi","year":2025,"journal":"Renal failure, 47(1), 2460720","doi":"10.1080/0886022X.2025.2460720","pmid":"39962730","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12489","title":"Wet Feeding Promotes Growth without Affecting Hypothalamic Peptide Gene Expression in Growing Broiler Chicks.","authors":"Matsunami, Tomoya; Zhang, Yuhui; Taniguchi, Yuji; Hinomoto, Sei-Ichi; Saneyasu, Takaoki; Kamisoyama, Hiroshi; Honda, Kazuhisa","year":2025,"journal":"The journal of poultry science, 62, 2025008","doi":"10.2141/jpsa.2025008","pmid":"39925947","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12490","title":"The effects of incretins as a double-edged sword on cancer.","authors":"Mavaddat, Helia; Fouladi, Abtin; Peyrovinasab, Amirreza; Khayatan, Illia; Jalalian Targhi, Hanieh; Fakhri, Mojdeh; Andarzbakhsh, Kamyab; Büsselberg, Dietrich; Razavi, Seyed Mehrad; Rezazadeh, Amir","year":2025,"journal":"Molecular biology reports, 52(1), 965","doi":"10.1007/s11033-025-11062-5","pmid":"41023473","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12491","title":"Comparison of the cardioprotective effects of liraglutide, dapagliflozin and their combination in a rat model of diabetes induced by streptozotocin.","authors":"Mayyas, Fadia; Omeish, Anood","year":2025,"journal":"Life sciences, 375, 123721","doi":"10.1016/j.lfs.2025.123721","pmid":"40389022","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12492","title":"Distribution and Neurochemical Characterization of Dorsal Root Ganglia (DRG) Neurons Containing Phoenixin (PNX) and Supplying the Porcine Uterine Cervix.","authors":"Mazur, Urszula; Kuśmierek, Paulina; Janikiewicz, Paweł; Majewski, Mariusz Krzysztof; Bossowska, Agnieszka","year":2025,"journal":"Cells, 14(23)","doi":"10.3390/cells14231847","pmid":"41369336","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12493","title":"Targeting with toxins: an overview of venom peptides in drug delivery.","authors":"Mazurs, Austris; Mauriņa, Baiba; Bandere, Dace; Logviss, Konstantīns","year":2025,"journal":"International journal of pharmaceutics, 685, 126193","doi":"10.1016/j.ijpharm.2025.126193","pmid":"40983118","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"This review synthesizes research on using venom-derived peptides as targeting agents for drug delivery. Chlorotoxin (from scorpion venom) and exendin-4 (from Gila monster venom) have shown the most promise. Venom peptides have been incorporated into nanoparticles and bioconjugates to deliver therapeutic and diagnostic agents, primarily targeting cancer and nervous system conditions. Their evolutionary refinement provides high potency and specificity for human biomolecules.","whyItMatters":"Many drugs fail because they can't reach their target or cause too many side effects elsewhere. Venom peptides, shaped by millions of years of evolution to precisely target specific biological molecules, offer a natural solution. Harnessing these peptides for drug delivery could dramatically improve treatment precision while reducing toxicity.","specificNumbers":"Multiple venom-derived peptides reviewed · chlorotoxin (scorpion) and exendin-4 (lizard) highlighted as most promising · nanoparticle and bioconjugate delivery systems","methodology":"Comprehensive literature review of research on venom-derived peptides used in targeted drug delivery systems, covering natural and modified peptide variants, nanoparticle and bioconjugate platforms, and applications in therapeutics and diagnostics.","limitations":"As a review, this synthesizes existing research without presenting new data. Most of the delivery systems discussed are still in preclinical or early development stages. The translation from lab-based targeting demonstrations to clinical drug delivery products remains challenging."},{"rthcId":"RPEP-12494","title":"The Thyroid Twist: How GLP-1 Agonists Are Influencing Autoimmune Thyroid Care.","authors":"Mazza, Angela D","year":2025,"journal":"Cureus, 17(11), e98153","doi":"10.7759/cureus.98153","pmid":"41479489","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12495","title":"Metabolic and renal effects of combined SGLT-2 inhibitors and GLP1-R agonists therapy in type 2 diabetes: a real-world analysis across DKD and non-DKD patients.","authors":"Mazzeo, L; Wolde Sellasie, S; Pecchioli, C; Di Perna, P; Zaccaria, S; Sperti, P; Nardone, I; Giurato, L; Della-Morte, D; Caprio, M; Bellia, A; Uccioli, L","year":2025,"journal":"Journal of endocrinological investigation","doi":"10.1007/s40618-025-02756-5","pmid":"41452441","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12496","title":"Significance of the LL-37 Peptide Delivered from Human Cathelicidin in the Pathogenesis, Treatment, and Diagnosis of Sepsis.","authors":"Mańkowska, Angelika; Paprocka, Paulina; Król, Grzegorz; Lesiak, Agata; Spałek, Jakub; Piktel, Ewelina; Okła, Sławomir; Bijak, Piotr; Niklińska, Wiesława; Durnaś, Bonita; Bucki, Robert","year":2025,"journal":"Archivum immunologiae et therapiae experimentalis, 73(1)","doi":"10.2478/aite-2025-0025","pmid":"40960088","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12497","title":"Evaluating the Prognostic Significance of Circulating Biomarkers of End Organ Damage in Hypertension.","authors":"Mbeta, Elliot; Williams, Katie; Yates, James; Sankaranarayanan, Rajiv; Penson, Peter; Lip, Gregory Y H; McDowell, Garry","year":2025,"journal":"Journal of clinical medicine, 14(17)","doi":"10.3390/jcm14175935","pmid":"40943694","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12498","title":"Capryol® 90 is an efficacious intestinal absorption enhancer for insulin in vivo when combined other excipients.","authors":"McCartney, Fiona; Caisse, Philippe; Dumont, Camille; Brayden, David J","year":2025,"journal":"International journal of pharmaceutics, 686, 126315","doi":"10.1016/j.ijpharm.2025.126315","pmid":"41161555","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12499","title":"Beyond glycated haemoglobin: Modelling contemporary management of type 2 diabetes with the updated Cardiff model.","authors":"McEwan, Phil; Foos, Volker; Roberts, Geraint; Jenkins, Robert H; Evans, Marc; Wheeler, David C; Chen, Jieling","year":2025,"journal":"Diabetes, obesity & metabolism, 27(4), 1752-1761","doi":"10.1111/dom.16141","pmid":"39828939","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The updated Cardiff T2D model incorporated three key changes: (1) a holistic therapy selection/escalation module considering cardiovascular risk, comorbidities, and bodyweight — not just HbA1c; (2) updated risk factor progression equations based on UKPDS90 data; (3) novel risk equations capturing cardio-kidney-metabolic benefits of SGLT2 inhibitors and GLP-1 receptor agonists derived from clinical outcomes trial data.\n\nComparing holistic vs. conventional (glucose-centric) approaches for a newly diagnosed T2D population, the holistic model enabled earlier introduction of SGLT2i and GLP-1 RA — primarily driven by elevated cardiovascular risk. This resulted in fewer predicted clinical events (cardiovascular, renal) and additional health benefits compared to the glucose-focused approach.","whyItMatters":"Health economic models drive real-world treatment decisions — they inform guidelines, insurance coverage, and prescribing policies. If these models focus only on blood sugar, they underestimate the value of GLP-1 drugs and SGLT2 inhibitors, potentially delaying access to medications that save lives. By updating the model to capture the full cardio-kidney-metabolic benefits of these drugs, this study provides the economic evidence needed to support modern guidelines that recommend earlier use of these therapies in high-risk patients.","specificNumbers":"","methodology":"The researchers updated the existing Cardiff T2D health economic model by replacing the conventional glucose-centric therapy selection module with a holistic decision framework. Risk equations were updated using UKPDS90 data, and novel equations were derived from SGLT2i and GLP-1 RA cardiovascular outcomes trials. The significance of the updates was tested by modeling predicted outcomes and costs for a newly diagnosed T2D population under both conventional (HbA1c-only) and holistic (multi-factor) treatment approaches.","limitations":"Health economic models are simplifications of reality and rely on assumptions about disease progression, treatment adherence, and costs that may not perfectly reflect individual patient experiences. The model outcomes are predictions, not observed clinical data. The novel risk equations for SGLT2i and GLP-1 RA benefits were derived from trial populations that may differ from real-world patients. The model does not account for all possible treatment combinations or patient preferences. Specific numerical outcomes (event rates, costs) are not detailed in the abstract."},{"rthcId":"RPEP-12500","title":"Cost-effectiveness of semaglutide in people with obesity and cardiovascular disease without diabetes.","authors":"McEwan, Phil; Bøg, Martin; Faurby, Mads; Foos, Volker; Lingvay, Ildiko; Lübker, Christopher; Miller, Ryan; Toliver, Joshua C; Yeates, Florian; Lincoff, A Michael","year":2025,"journal":"Journal of medical economics, 28(1), 268-278","doi":"10.1080/13696998.2025.2459529","pmid":"39882599","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12501","title":"Clinical Effectiveness of Semaglutide for Weight Loss in a Veterans Affairs' Anti-Obesity Pharmacotherapy Clinic.","authors":"McGinnis, Timothy; McCallum, Molly; Pan, Zhaoxing; Cunningham, Christina; Saxon, David R; Thomas, Elizabeth","year":2025,"journal":"Journal of general internal medicine","doi":"10.1007/s11606-025-09943-3","pmid":"41233692","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12502","title":"Oral Semaglutide and Cardiovascular Outcomes in High-Risk Type 2 Diabetes.","authors":"McGuire, Darren K; Marx, Nikolaus; Mulvagh, Sharon L; Deanfield, John E; Inzucchi, Silvio E; Pop-Busui, Rodica; Mann, Johannes F E; Emerson, Scott S; Poulter, Neil R; Engelmann, Mads D M; Ripa, Maria Sejersten; Hovingh, G Kees; Brown-Frandsen, Kirstine; Bain, Stephen C; Cavender, Matthew A; Gislum, Mette; David, Jens-Peter; Buse, John B","year":2025,"journal":"The New England journal of medicine, 392(20), 2001-2012","doi":"10.1056/NEJMoa2501006","pmid":"40162642","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 9,650 randomized participants with type 2 diabetes and atherosclerotic cardiovascular disease, chronic kidney disease, or both:\n\n- **Primary outcome (MACE)**: 12.0% in the oral semaglutide group vs. 13.8% in the placebo group (HR 0.86; 95% CI 0.77-0.96; P = 0.006)\n- Incidence rates: 3.1 vs. 3.7 events per 100 person-years\n- Mean follow-up: 47.5 months (median 49.5 months)\n- The confirmatory secondary outcome of major kidney disease events did not differ significantly between groups\n- Serious adverse events: 47.9% vs. 50.3% (numerically lower with semaglutide)\n- Gastrointestinal disorders: 5.0% vs. 4.4% (slightly higher with semaglutide, as expected)","whyItMatters":"While injectable semaglutide had already shown cardiovascular benefits, this is the first large-scale trial proving the oral formulation also protects the heart. For the millions of patients who prefer pills over injections, this is a game-changer — they can now get cardiovascular protection from an oral GLP-1 drug. Published in the NEJM with nearly 10,000 participants and 4 years of follow-up, this represents the highest tier of clinical evidence.","specificNumbers":"","methodology":"This was a double-blind, placebo-controlled, event-driven, superiority trial (SOUL). Participants aged 50+ with type 2 diabetes (HbA1c 6.5-10.0%) and established atherosclerotic cardiovascular disease, chronic kidney disease, or both were randomized to once-daily oral semaglutide (up to 14 mg) or placebo, added to standard care. The primary outcome was time to first major adverse cardiovascular event (MACE: cardiovascular death, nonfatal MI, or nonfatal stroke).","limitations":"The confirmatory secondary outcome for kidney disease events was not significantly different, so oral semaglutide's renal benefits remain unproven. The trial population was predominantly high-risk with established cardiovascular or kidney disease, so results may not generalize to lower-risk patients. The maximum oral dose of 14 mg is lower than injectable semaglutide doses used for weight loss, and the cardiovascular benefit may be partially driven by weight loss and metabolic improvements rather than direct cardiac effects. The trial was funded by Novo Nordisk, the manufacturer."},{"rthcId":"RPEP-12503","title":"Regeneration or Risk? A Narrative Review of BPC-157 for Musculoskeletal Healing.","authors":"McGuire, Flynn P; Martinez, Riley; Lenz, Annika; Skinner, Lee; Cushman, Daniel M","year":2025,"journal":"Current reviews in musculoskeletal medicine, 18(12), 611-619","doi":"10.1007/s12178-025-09990-7","pmid":"40789979","tags":["bpc-157","musculoskeletal","tendon-healing"],"studyType":"Scoping Review","evidenceStrength":"Moderate","keyFinding":"BPC-157 activates several key healing pathways in animal models: VEGFR2 and nitric oxide synthesis via the Akt-eNOS axis (promoting blood vessel growth), ERK1/2 signaling (facilitating tissue repair), fibroblast activation, and anti-inflammatory effects. These mechanisms are particularly relevant for poorly vascularized tissues like tendons and myotendinous junctions, which heal slowly.\n\nHowever, the review found a stark gap between preclinical promise and clinical evidence. Only three small pilot studies have examined BPC-157 in humans: for knee pain (intraarticular), interstitial cystitis, and IV safety/pharmacokinetics. No adverse effects were reported in any human study, but none were powered to assess efficacy. The review concludes that BPC-157 should be considered investigational until well-designed clinical trials are completed.","whyItMatters":"BPC-157 has become one of the most popular peptides among athletes and wellness seekers, widely available through unregulated sources despite having almost no human clinical data. This 2025 review from a musculoskeletal medicine journal provides the most current, balanced assessment — acknowledging the robust preclinical evidence while clearly stating that human data is minimal. It directly calls for rigorous clinical trials, reflecting the growing tension between public demand and scientific evidence.","specificNumbers":"Only 3 human pilot studies exist · mechanisms: VEGFR2, Akt-eNOS, ERK1/2 · 0 adverse events reported in humans · numerous positive animal models · FDA regulatory controversy noted","methodology":"Scoping review evaluating the molecular mechanisms, therapeutic potential, and safety profile of BPC-157 for musculoskeletal applications. The authors assessed the breadth and quality of both preclinical (animal) and clinical (human) data, with particular attention to mechanism of action pathways and regulatory status.","limitations":"The review is narrative/scoping rather than systematic, meaning the search strategy and inclusion criteria may not be as rigorous as a full systematic review. The field itself is limited by the dominance of a single research group (Sikiric et al.) in the preclinical literature. The three human studies are all small pilots without control groups. The regulatory landscape for BPC-157 is complex and varies by jurisdiction, adding uncertainty about product quality from non-pharmaceutical sources."},{"rthcId":"RPEP-12504","title":"Circulating Cardiovascular Proteomic Associations With Genetics and Disease.","authors":"McGurk, Kathryn A; Curran, Lara; Sau, Arunashis; Ng, Fu Siong; Halliday, Brian; Ware, James S; O'Regan, Declan P","year":2025,"journal":"Circulation. Genomic and precision medicine, 18(6), e005005","doi":"10.1161/CIRCGEN.124.005005","pmid":"41054850","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12505","title":"Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and suicidality: A replication study using reports to the World Health Organization pharmacovigilance database (VigiBase®).","authors":"McIntyre, Roger S; Mansur, Rodrigo B; Rosenblat, Joshua D; Rhee, Taeho Greg; Cao, Bing; Teopiz, Kayla M; Wong, Sabrina; Le, Gia Han; Ho, Roger; Kwan, Angela T H","year":2025,"journal":"Journal of affective disorders, 369, 922-927","doi":"10.1016/j.jad.2024.10.062","pmid":"39433133","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Using the WHO VigiBase database, reporting odds ratios (ROR) showed a mixed pattern:\n\n**Increased ROR (more reports than expected):**\n- Suicidal ideation: semaglutide (5.82), liraglutide (4.03), tirzepatide (2.25)\n- Depression/suicidal: semaglutide (14.74), liraglutide (5.86)\n- Suicidal behavior: semaglutide (6.52), liraglutide (3.90)\n\n**Decreased ROR (fewer reports than expected):**\n- Suicide attempts: semaglutide (0.11), dulaglutide (0.075), exenatide (0.047), liraglutide (0.15)\n- Completed suicide: semaglutide (0.01), dulaglutide (0.003), exenatide (0.002), liraglutide (0.008)\n\nThis paradoxical pattern — more reports of suicidal thoughts but dramatically fewer actual attempts and deaths — differs from what was found in the FDA's FAERS database.","whyItMatters":"With tens of millions of people now taking GLP-1 drugs like semaglutide, any potential link to suicidality would be a major public health concern. Both the EMA and FDA have investigated this signal. This WHO database analysis — the largest global pharmacovigilance database — provides important context by revealing a paradoxical pattern that neither clearly supports nor refutes a causal link, highlighting the limitations of spontaneous reporting data for answering this critical safety question.","specificNumbers":"","methodology":"Researchers searched the WHO global pharmacovigilance database (VigiBase) from inception through January 2024 for reports of suicidality associated with GLP-1 receptor agonists. Reporting odds ratios (ROR) were calculated for different suicidality outcomes (ideation, depression/suicidal, suicidal behavior, suicide attempts, completed suicide) for each GLP-1 RA. An ROR was considered significant when the lower limit of the 95% confidence interval exceeded 1.0.","limitations":"Pharmacovigilance databases like VigiBase capture spontaneous reports, which are subject to severe reporting biases — including stimulated reporting (increased reports due to media attention), underreporting, and inability to establish causation. The study cannot account for underlying depression or suicidality risk in the patient populations taking GLP-1 drugs (obesity and diabetes both independently increase suicide risk). The paradoxical findings (more ideation, fewer attempts/deaths) suggest that reporting artifacts, rather than true drug effects, may be driving the signal."},{"rthcId":"RPEP-12506","title":"Potential protective role of GLP-1 receptor agonists for lithium-induced nephrotoxicity: a population-based observational study.","authors":"McIntyre, Roger S; Kwan, Angela T H","year":2025,"journal":"CNS spectrums, 31(1), e5","doi":"10.1017/S1092852925100709","pmid":"41220244","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12507","title":"Implications of GLP-1 Agonists on Office-Based Sedation and General Anesthesia for Dentistry.","authors":"McKenzie, Craig; DeBernardo, Alexander; Schwartz, Paul","year":2025,"journal":"Anesthesia progress, 72(1), 52-58","doi":"10.2344/anpr-72-1-ANPR_Agonists","pmid":"40657828","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12508","title":"Evaluation of Insulin Dosage After the Addition of Tirzepatide Compared With Semaglutide or Dulaglutide in Patients With Type 2 Diabetes.","authors":"McKone, Delaney B; Duprey, Karolyn S; Hall, Hayley M; Leonhard, Abigail; Schadler, Aric; Naseman, Kristina W","year":2025,"journal":"Diabetes spectrum : a publication of the American Diabetes Association, 38(3), 266-273","doi":"10.2337/ds24-0035","pmid":"40823594","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12509","title":"Addressing Meta-Inflammation in the Comprehensive Management of Chronic Pain.","authors":"McMasters, Morgan; Mora, Jorge","year":2025,"journal":"Cureus, 17(10), e94863","doi":"10.7759/cureus.94863","pmid":"41257114","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12510","title":"Incretin receptor agonism rapidly inhibits AgRP neurons to suppress food intake in mice.","authors":"McMorrow, Hayley E; Cohen, Andrew B; Lorch, Carolyn M; Hayes, Nikolas W; Fleps, Stefan W; Frydman, Joshua A; Xia, Jessica L; Samms, Ricardo J; Beutler, Lisa R","year":2025,"journal":"The Journal of clinical investigation, 135(21)","doi":"10.1172/JCI186652","pmid":"40857106","tags":["glp-1-receptor-agonists"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Using fiber photometry in live mice, researchers discovered that GIP and GLP-1 play distinct roles in appetite regulation through AgRP neurons — the brain's key hunger-promoting cells. Endogenous GIP (but not GLP-1) was required for normal nutrient-triggered suppression of these hunger neurons. However, at pharmacologic doses, both GIP and GLP-1 analogs inhibited AgRP neurons.\n\nCritically, dual GIP and GLP-1 receptor agonism (as in tirzepatide) more potently inhibited AgRP neurons and suppressed food intake than either agonist alone. The degree of neural inhibition directly correlated with how much each drug reduced eating.","whyItMatters":"Semaglutide and tirzepatide are blockbuster obesity drugs, but scientists still don't fully understand how they suppress appetite in the brain. This study identifies a specific neural mechanism — inhibition of AgRP hunger neurons — and reveals why dual agonists like tirzepatide may work better than GLP-1-only drugs like semaglutide. Understanding these pathways is essential for designing next-generation weight loss drugs that are more effective and have fewer side effects.","specificNumbers":"Dual GIP/GLP-1 agonism > single agonism for AgRP inhibition · Neural inhibition magnitude proportional to food intake reduction · GIP required for normal nutrient-mediated AgRP suppression · GLP-1 not required for physiologic AgRP inhibition","methodology":"Researchers used in vivo fiber photometry to monitor real-time activity of AgRP neurons in living mice. They tested the effects of endogenous incretin hormones (GIP and GLP-1) during normal feeding, as well as pharmacologic doses of incretin analogs, on AgRP neuron activity and food intake. They compared single versus dual receptor agonism.","limitations":"This was a mouse study, and the neural circuits controlling appetite differ somewhat between mice and humans. The pharmacologic doses used may not directly correspond to clinical doses in humans. The study focused on one neural population (AgRP neurons) when incretin drugs likely affect multiple brain circuits."},{"rthcId":"RPEP-12511","title":"Suspected liraglutide (glucagon-like peptide-1 receptor agonist)-induced hyperthyroidism: A case report.","authors":"Md Sabudin, Siti Nur Syakinah; Yaacob, Lili Husniati; Che Omar, Muhammad Rahmat","year":2025,"journal":"Malaysian family physician : the official journal of the Academy of Family Physicians of Malaysia, 20, 58","doi":"10.51866/cr.886","pmid":"40949169","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12512","title":"Peptide Vaccines for Pediatric High-Grade Glioma and Diffuse Midline Glioma: Current Progress and Future Perspectives.","authors":"Mebrahtu, Aron K; Jain, Vatsal; Moelker, Eliese M; Hoyt-Miggelbrink, Alexandra M; Ayasoufi, Katayoun; Thompson, Eric M","year":2025,"journal":"Vaccines, 13(12)","doi":"10.3390/vaccines13121215","pmid":"41441679","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12513","title":"Segment-Based Peptide Design Reveals the Importance of N-Terminal High Cationicity for Antimicrobial Activity Against Gram-Negative Pathogens.","authors":"Mechesso, Abraham Fikru; Zhang, Weiwei; Su, Yajuan; Xie, Jingwei; Wang, Guangshun","year":2025,"journal":"Probiotics and antimicrobial proteins, 17(1), 15-34","doi":"10.1007/s12602-024-10376-3","pmid":"39377976","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12514","title":"Erenumab for Chronic Cluster Headache: A Randomized Clinical Trial.","authors":"Mecklenburg, Jasper; Gaul, Charly; Fitzek, Mira; Overeem, Lucas H; Heinze, Axel; Fleischmann, Robert; Boeger, Andreas; Holle-Lee, Dagny; Straube, Andreas; Gendolla, Astrid; Israel-Willner, Heike; Lorenz, Mario; Gossrau, Gudrun; Naegel, Steffen; Rimmele, Florian; Rattan, Simrit; Materne, Bianca; Schulze, Daniel; Raffaelli, Bianca; Reuter, Uwe","year":2025,"journal":"JAMA network open, 8(6), e2516318","doi":"10.1001/jamanetworkopen.2025.16318","pmid":"40526384","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12515","title":"Incretin-Based Therapies and Cancer: What's New?","authors":"Medenica, Sanja; Bogdanovic, Jelena; Vekic, Jelena; Vojinovic, Tanja; Babic, Ivana; Bogdanović, Ljiljana; Maggio, Viviana; Tanani, Mohamed El; Rizzo, Manfredi","year":2025,"journal":"Medicina (Kaunas, Lithuania), 61(4)","doi":"10.3390/medicina61040678","pmid":"40282969","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12516","title":"GLP-1RA in the Real World: 1-year Compliance and Outcomes of Semaglutide use in Patients With or Without Previous History of Bariatric Surgery.","authors":"Medhati, Pourya; Shin, Thomas H; Wasden, Katherine; Mathur, Vasundhara; Apovian, Caroline; Nimeri, Abdelrahman; Sheu, Eric G; Tavakkoli, Ali","year":2025,"journal":"Annals of surgery","doi":"10.1097/SLA.0000000000006748","pmid":"40334053","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12517","title":"Lactic acid bacteria as microbial cell factories for the in vivo delivery of therapeutic proteins as secretable TAT fusion products.","authors":"Medici, Giorgio; Candini, Giulia; Mottolese, Nicola; Uguagliati, Beatrice; Trebbi, Federica; Loi, Manuela; Bove, Angelica Marina; Stojanov, Spase; Esposito, Erika; Vitagliano, Rosalba; D'Amico, Federica; Turroni, Silvia; Fiori, Jessica; Berlec, Aleš; Trazzi, Stefania; Ciani, Elisabetta","year":2025,"journal":"Journal of biological engineering, 19(1), 65","doi":"10.1186/s13036-025-00538-4","pmid":"40676698","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12518","title":"Emerging Electrochemical and Biosensing Platforms for Troponin I and B-Type Natriuretic Peptide: A Comprehensive Insight into Next-Generation Cardiac Diagnostics.","authors":"Meenakumari Gopakumar, Devika; Meenakumari Gopakumar, Gopika","year":2025,"journal":"Critical reviews in analytical chemistry, 1-20","doi":"10.1080/10408347.2025.2599306","pmid":"41369095","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12519","title":"Neurochemical heterogeneity of ChAT-immunoreactive neurons in the basal forebrain cholinergic nuclei and striatum in reference to CGRP, CCK, and calcium-binding proteins.","authors":"Meher, Mirza Mienur; Afrin, Marya; Jahan, Mir Rubayet; Nozaki, Kanako; Masumoto, Koh-Hei; Yanai, Akie; Islam, Md Nabiul","year":2025,"journal":"Acta histochemica, 127(4), 152291","doi":"10.1016/j.acthis.2025.152291","pmid":"40925258","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12520","title":"Design and fabrication of a mesoporous silica scaffold for oral delivery of peptides.","authors":"Mehmood, Yasir; Shahid, Hira; Siddique, Rida; Farooq, Umar; Rizvi, Syeda Momena; Uddin, Mohammad N; Kazi, Mohsin; Bourhia, Mohammed; Dabiellil, Fakhreldeen; Al Mughram, Mohammed H","year":2025,"journal":"Scientific reports, 15(1), 29520","doi":"10.1038/s41598-025-12728-7","pmid":"40796593","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12521","title":"Nutritional Challenges in Post-Massive Weight Loss Body Contouring: Guidance for Plastic Surgeons on GLP-1 Agonists and Sleeve Gastrectomy.","authors":"Mehta, Meeti; Rometo, David; Gusenoff, Jeffrey; Rubin, J Peter","year":2025,"journal":"Plastic and reconstructive surgery","doi":"10.1097/PRS.0000000000012672","pmid":"41329155","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 receptor agonists like semaglutide and tirzepatide suppress appetite and delay gastric emptying, which can further reduce protein and micronutrient intake in patients already at nutritional risk from weight loss. Despite guidelines recommending 60-120 g/day of protein, many patients on GLP-1RAs fall short of this target.\n\nProtein deficiency is particularly dangerous for surgical patients because it impairs collagen production, angiogenesis (new blood vessel formation), and immune function — all critical for wound healing. Laparoscopic sleeve gastrectomy, while causing fewer malabsorption issues than gastric bypass, still predisposes patients to iron, B12, and protein deficiencies due to reduced food intake and food intolerance.","whyItMatters":"The explosion of GLP-1 medications for weight loss is creating a new and rapidly growing population of massive weight loss patients seeking body contouring surgery. These patients present different nutritional profiles than traditional bariatric surgery patients, and many plastic surgeons may not be aware of the specific risks. Poor nutritional status can lead to wound healing complications, infections, and poor surgical outcomes — making preoperative nutritional optimization essential.","specificNumbers":"","methodology":"The authors conducted a narrative review providing clinical guidance for plastic surgeons. They examined the nutritional impacts of both bariatric surgery (particularly sleeve gastrectomy vs. gastric bypass) and GLP-1 receptor agonists on body contouring surgery outcomes. The review synthesized existing evidence into practical perioperative recommendations.","limitations":"This is a narrative review providing expert guidance rather than original clinical data. The specific incidence of nutritional deficiencies in GLP-1RA patients undergoing body contouring is not quantified with original research. Recommendations are based on extrapolation from bariatric surgery nutrition literature and general wound healing principles rather than GLP-1-specific surgical outcome studies."},{"rthcId":"RPEP-12522","title":"Identification of Novel Umami Peptides from Yak Bone Collagen and Mechanism Exploration Through In Silico Discovery, Molecular Docking, and Electronic Tongue.","authors":"Mei, Yimeng; Wu, Xiaoli; Xie, Ruoyu; Wu, Yulong; Du, Hongying; Chen, Wenxuan; Hu, Jun; Zhao, Ke; Guo, Runfang; Zhang, Jin","year":2025,"journal":"Foods (Basel, Switzerland), 14(23)","doi":"10.3390/foods14234057","pmid":"41375997","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12523","title":"From sensation to regulation: the diverse functions of peripheral sensory nervous system.","authors":"Mei, Yixiao; Zhou, Bing-Lin; Zhong, Da; Zheng, Xuan-Jie; Deng, Yu-Tao; Yu, Lina; Jiang, Bao-Chun","year":2025,"journal":"Frontiers in immunology, 16, 1575917","doi":"10.3389/fimmu.2025.1575917","pmid":"40453085","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12524","title":"The Black Soldier Fly Hermetia illucens Larva Presents an Antimicrobial Activity in Response to Clostridioides difficile Exposure.","authors":"Melchior, Aviel; Azrad, Maya; Fichtman, Boris; Peretz, Avi","year":2025,"journal":"Current research in microbial sciences, 9, 100469","doi":"10.1016/j.crmicr.2025.100469","pmid":"41467043","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12525","title":"Anemia risk and mitigation strategies in type 2 diabetic patients: The role of novel antidiabetic agents.","authors":"Meliš, Petra; Cigrovski Berkovic, Maja","year":2025,"journal":"World journal of diabetes, 16(5), 105549","doi":"10.4239/wjd.v16.i5.105549","pmid":"40487613","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies anemia as a prevalent but under-recognized complication in type 2 diabetes, particularly in patients with chronic kidney disease. It examines three classes of newer antidiabetic agents — SGLT2 inhibitors, GLP-1 receptor agonists, and combined GLP-1 RA/GIP agonists — for their potential effects on anemia risk.\n\nThe authors highlight that current clinical guidelines lack specific recommendations for anemia prevention and management in the context of these newer therapies, representing a significant gap in diabetes care. Early detection and management of anemia is emphasized as important for glycemic control, cardiovascular outcomes, and overall treatment success.","whyItMatters":"As GLP-1-based therapies become first-line treatments for millions of diabetes patients, understanding their effects on conditions like anemia is essential. Anemia worsens cardiovascular disease — already the leading cause of death in diabetes — so any drug that reduces anemia risk could provide significant additional benefit beyond blood sugar control.","specificNumbers":"","methodology":"This is a narrative review of existing literature examining the relationship between type 2 diabetes, anemia, and newer antidiabetic medications. The authors reviewed published research on SGLT2 inhibitors, GLP-1 receptor agonists, and GLP-1 RA/GIP dual agonists with respect to their effects on anemia risk and hematological parameters.","limitations":"As a narrative review, this does not present original data or conduct a systematic search. The mechanisms by which GLP-1 RAs and GLP-1/GIP agonists might influence anemia are not yet well-established. The review acknowledges that further research is needed to understand these relationships, meaning current conclusions are largely hypothesis-generating rather than definitive."},{"rthcId":"RPEP-12526","title":"A Conceptual Review of Naturally Occurring Toxins and Venoms as Peptide Blockers to Combat Chronic Low Back Pain.","authors":"Melrose, James; Sima, Stone; Chopra, Neha; Diwan, Ashish; Gu, Zi","year":2025,"journal":"JOR spine, 8(3), e70107","doi":"10.1002/jsp2.70107","pmid":"40821360","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12527","title":"What is the pipeline for future medications for obesity?","authors":"Melson, Eka; Ashraf, Uzma; Papamargaritis, Dimitris; Davies, Melanie J","year":2025,"journal":"International journal of obesity (2005), 49(3), 433-451","doi":"10.1038/s41366-024-01473-y","pmid":"38302593","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12528","title":"Drug adherence, glycemic control, and weight reduction with subcutaneous semaglutide in real-world management of type 2 diabetes.","authors":"Melzer Cohen, Cheli; Mosenzon, Ofri; Aharonovich, Alona; Karasik, Avraham; Schechter, Meir","year":2025,"journal":"Diabetes research and clinical practice, 222, 112086","doi":"10.1016/j.diabres.2025.112086","pmid":"40058653","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12529","title":"New Frontiers in Fighting Mycobacterial Infections: Venom-Derived Peptides.","authors":"Memariani, Hamed; Memariani, Mojtaba","year":2025,"journal":"Probiotics and antimicrobial proteins, 17(3), 1217-1235","doi":"10.1007/s12602-025-10455-z","pmid":"39828882","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12530","title":"Combining clinical markers can predict mortality in NYHA IV heart failure.","authors":"Men, Yi-Jiao; Dong, Yan-Ling; Gong, Yu; An, Ya-Qing; Cheng, Hong-Bo","year":2025,"journal":"Scientific reports, 15(1), 28721","doi":"10.1038/s41598-025-13274-y","pmid":"40770313","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12531","title":"PeptideMiner-neuropeptide discovery across the animal kingdom.","authors":"Mendel, Helen C; Hopping, Gene; Undheim, Eivind A B; Zuegg, Johannes; Lewis, Richard J; Forbes, Briony E; Kaas, Quentin; Muttenthaler, Markus","year":2025,"journal":"GigaScience, 14","doi":"10.1093/gigascience/giaf078","pmid":"40796375","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"PeptideMiner uses profile-hidden Markov models to discover peptide families across species despite high sequence divergence. Benchmarking showed it outperformed existing methods.\n\nApplied to venom transcriptomes (including 24 previously unpublished datasets), PeptideMiner identified 10 novel natriuretic peptides from distantly related species and 57 novel insulin-like sequences from marine cone snails. Chemical synthesis and testing of newly identified conoinsulins at human insulin receptors confirmed biological activity, validating the approach for discovering pharmacologically relevant peptides.","whyItMatters":"Only a fraction of the estimated neuropeptide diversity has been functionally characterized. PeptideMiner accelerates discovery by finding peptides that other tools miss due to sequence divergence. The cone snail insulin-like peptides are particularly exciting because nature has already evolved molecules that interact with human drug targets.","specificNumbers":"","methodology":"The researchers built PeptideMiner using profile-hidden Markov models trained on known neuropeptide families. They validated it against existing methods using benchmark datasets, then applied it to venom transcriptome databases including 24 new datasets. Newly discovered insulin-like peptides from cone snails were chemically synthesized and tested for activity at human insulin receptors.","limitations":"While PeptideMiner outperformed existing methods, no computational tool can find all peptides — novel families with no known relatives will still be missed. The functional characterization was limited to insulin receptor binding; in vivo efficacy, toxicity, and pharmacokinetics of the new peptides were not assessed. The tool depends on available transcriptome and genome data quality."},{"rthcId":"RPEP-12532","title":"Glucose metabolism impairment in major depressive disorder.","authors":"Meng, Fanhao; Wang, Jing; Wang, Long; Zou, Wei","year":2025,"journal":"Brain research bulletin, 221, 111191","doi":"10.1016/j.brainresbull.2025.111191","pmid":"39788458","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Patients with MDD show systemic and localized glucose metabolism impairments across multiple processes: glucose uptake, glycoprotein transport, glycolysis, the TCA cycle, and oxidative phosphorylation. These impairments stem from insulin resistance, hyperglycemia-induced damage, oxidative stress, astrocyte dysfunction, and mitochondrial dysfunction.\n\nThe downstream consequences include insufficient energy supply to neurons, altered synaptic plasticity, neuronal cell death, and functional/structural damage to brain reward networks — all of which contribute to depressive symptoms. GLP-1 receptor agonists, liraglutide, metformin, topical insulin, and pioglitazone are identified as potential pharmacological interventions that target these metabolic pathways.","whyItMatters":"Current antidepressants primarily target neurotransmitter systems (serotonin, norepinephrine, dopamine), but roughly one-third of patients don't respond adequately to these treatments. If depression has metabolic roots — as this review argues — then metabolic drugs like GLP-1 receptor agonists could offer an entirely new treatment approach. This is especially relevant given that GLP-1 drugs are already widely available and some patients on them report mood improvements.","specificNumbers":"","methodology":"This is a narrative review summarizing published research on glucose metabolism impairments in major depressive disorder. The authors synthesized findings from clinical studies, neuroimaging research, and basic science to map the pathophysiological mechanisms connecting metabolic dysfunction to depression, and briefly discussed potential metabolic drug interventions.","limitations":"As a narrative review, the paper synthesizes existing evidence but does not present new data or perform systematic analysis. Many of the metabolic drug interventions discussed for depression are based on preclinical data or small clinical studies — large-scale randomized trials specifically testing GLP-1 drugs as antidepressants are still needed. The review also acknowledges that the exact pathogenesis of MDD remains unclear, and metabolic impairment is likely one of many contributing factors."},{"rthcId":"RPEP-12533","title":"Enhancing leuprolide penetration through enterocytes via the ER-Golgi pathway using lipophilic complexation.","authors":"Meng, Jia; Chan, May Yee; Peng, Cheng; Jiang, Xuling; Qian, Feng","year":2025,"journal":"European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 207, 114624","doi":"10.1016/j.ejpb.2024.114624","pmid":"39733960","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12534","title":"Lowering B-type natriuretic peptide levels and increasing cardiac function: the role of levosimendan in the treatment of heart failure.","authors":"Meng, Jianfeng; Zuo, Ye","year":2025,"journal":"The Journal of international medical research, 53(2), 3000605241311434","doi":"10.1177/03000605241311434","pmid":"39922797","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12535","title":"Ivabradine Versus Up-titrated Bisoprolol for Persistent Tachycardia After Primary PCI in Anterior STEMI: A Single-center, Open-label, Pragmatic RCT.","authors":"Meng, Jianqiang; Ma, Hailiang; Zhu, Dewen; Lu, Yuanben; Jiang, Zhenhua","year":2025,"journal":"Cardiovascular drugs and therapy","doi":"10.1007/s10557-025-07801-2","pmid":"41144139","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12536","title":"Emerging technologies for early risk stratification and precision management of diabetic kidney disease: a multimodal framework integrating digital phenotypes and clinical biomarkers.","authors":"Meng, Lingdong; Li, Zhen; Xu, Ling; Wei, Fang; Ji, Hongyan; Zhang, Lankun; Zhu, Anning; Zhou, Zhijia","year":2025,"journal":"Frontiers in endocrinology, 16, 1728293","doi":"10.3389/fendo.2025.1728293","pmid":"41585789","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12537","title":"Dapagliflozin combined with sacubitril/valsartan promotes cardiac function recovery in elderly patients with acute myocardial infarction.","authors":"Meng, Pu; Zhen, Chuhao; Liu, Fan; Li, Xia","year":2025,"journal":"American journal of translational research, 17(9), 7482-7492","doi":"10.62347/QLUA3216","pmid":"41113014","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12538","title":"The comparative study of the efficacy of recombinant human brain natriuretic peptide combined with vasoactive medications for elderly patients with heart failure and hypotension receiving injections.","authors":"Meng, Rui; Li, Xiangnan; Liu, Huimin; Yi, Zhong; Han, Yalei; Xie, Qing; Xiu, Helu; Yao, Fei; Guo, Na; Yu, Yan","year":2025,"journal":"BMC cardiovascular disorders, 25(1), 185","doi":"10.1186/s12872-025-04609-8","pmid":"40089700","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12539","title":"A branched peptide targets virus and host to block influenza virus and rhinovirus entry.","authors":"Meng, Xinjie; Zhang, Chuyuan; Wang, Xiankun; Shi, Jilong; Song, Zixian; Ke, Purui; Chen, Yao; Sun, Ruiqing; Lau, Yee-Man; Ng, Kwong-Man; Wong, Chun-Ka; Tse, Hung-Fat; Chen, Linlei; Chan, Kwok Hung; Yip, Cyril Chik-Yan; Zhou, Jie; Xie, Youhua; Jiang, Shibo; To, Kelvin Kai-Wang; Yuen, Kwok-Yung; Zhao, Hanjun","year":2025,"journal":"Antimicrobial agents and chemotherapy, 69(8), e0002425","doi":"10.1128/aac.00024-25","pmid":"40560073","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12540","title":"Reduction of Neuroinflammation as a Common Mechanism of Action of Anorexigenic and Orexigenic Peptide Analogues in the Triple Transgenic Mouse Model of Alzheimer´s Disease.","authors":"Mengr, Anna; Šmotková, Zuzana; Pačesová, Andrea; Železná, Blanka; Kuneš, Jaroslav; Maletínská, Lenka","year":2025,"journal":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology, 20(1), 18","doi":"10.1007/s11481-025-10174-w","pmid":"39932627","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12541","title":"Metachronous Occurrence of Acute Myeloid Leukaemia in a Case of Neuroendocrine Tumour.","authors":"Menon, Abhinav; Harindran Vallathol, Dilip; Charles, Deepak; Nair, Shagos; Kundil Veetil, Karthika; Komaranchath, Ashok S; Warrier, Arun R","year":2025,"journal":"European journal of case reports in internal medicine, 12(4), 005233","doi":"10.12890/2025_005233","pmid":"40270677","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The patient, an elderly woman with a metastatic pancreatic neuroendocrine tumor (pNET), developed acute myeloid leukemia (AML) while receiving peptide receptor radionuclide therapy (PRRT) with octreotide. The AML diagnosis was complicated by pancytopenia that initially masked the leukemia.\n\nShe was treated with a non-chemotherapy regimen of azacitidine and venetoclax, which achieved remission of both the AML and the neuroendocrine tumor simultaneously. This dual response demonstrates the potential for non-intensive therapeutic approaches in managing therapy-related AML in complex oncology patients.","whyItMatters":"PRRT is an increasingly used treatment for neuroendocrine tumors, and as more patients survive longer on this therapy, the long-term risks — including secondary blood cancers — become more relevant. This case demonstrates that therapy-related AML can develop during PRRT and may be initially obscured by the blood count changes caused by the radiation. Importantly, it shows a successful non-chemotherapy management strategy, which is valuable for patients who may not tolerate aggressive treatment.","specificNumbers":"","methodology":"This is a clinical case report documenting the sequential management of a metastatic neuroendocrine tumor with PRRT (using radiolabeled octreotide) and the subsequent development and treatment of secondary AML. The case was managed through a multidisciplinary tumor board approach.","limitations":"This is a single case report and cannot establish the frequency of secondary AML following PRRT or the generalizability of the non-chemotherapy treatment approach. The causal relationship between PRRT and AML development cannot be definitively established from one case — the leukemia could have developed independently. The long-term durability of the dual remission is not reported."},{"rthcId":"RPEP-12542","title":"Unraveling the obesity-asthma link: A new horizon with glucagon-like peptide-1 receptor agonists in a complex intersection of metabolism and airway disease.","authors":"Menzella, Francesco; Cottini, Marcello; Chan, Rory","year":2025,"journal":"The Journal of international medical research, 53(11), 3000605251392717","doi":"10.1177/03000605251392717","pmid":"41193498","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12543","title":"Metabolic Improvements With Tirzepatide in Lipodystrophy: A Novel Option?","authors":"Meral, Rasimcan; Celik Guler, Merve; Kaba, Diarratou; Prativadi, Jeevitha; Frontera, Eric D; Foss-Freitas, Maria Cristina; Nachawi, Noura; Broome, David T; Lightbourne, Marissa; Brown, Rebecca J; Taylor, Simeon I; Oral, Elif A","year":2025,"journal":"Diabetes care, 48(5), 756-762","doi":"10.2337/dc24-2408","pmid":"40063619","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"After a median 8.7 months of tirzepatide treatment in 17 lipodystrophy patients (14 with FPLD): BMI decreased by median 1.7 kg/m² (p=0.008), HbA1c decreased by median 1.1% (range -6.3% to -0.1%, p<0.001), triglycerides decreased by median 65 mg/dL (with one patient dropping 3,820 mg/dL; p=0.003), and total daily insulin requirements decreased by median 109 units (range -315 to 0 units, p=0.002). Three additional patients with rarer lipodystrophy forms (atypical PL, acquired GL) also showed robust responses. Side effects were limited to benign gastrointestinal symptoms.","whyItMatters":"Lipodystrophy patients face severe metabolic complications with very limited treatment options — the only approved therapy (metreleptin) has significant limitations. Many patients require hundreds of units of insulin daily and still have dangerously high blood sugar and triglycerides. Finding that tirzepatide dramatically improves these parameters, including reducing insulin needs by over 100 units daily, could transform care for this rare disease population.","specificNumbers":"","methodology":"Observational cohort study of lipodystrophy patients receiving tirzepatide as part of clinical care, tracked within ongoing natural history studies. Seventeen patients were followed for a median of 8.7 months. Outcomes included BMI, HbA1c, triglycerides, and total daily insulin requirements. Statistical significance was assessed using non-parametric tests given the small sample size. Three additional rare lipodystrophy cases were described.","limitations":"Very small observational cohort (17 patients) without a control group — the gold standard for treatment evaluation. Results could be influenced by concurrent medications, dietary changes, or natural disease fluctuation. The wide ranges in outcomes (e.g., triglyceride reduction from -3,820 to +43 mg/dL) indicate highly variable individual responses. Published in Diabetes Care as a report rather than a randomized trial. The rare nature of lipodystrophy inherently limits sample sizes, but this means the evidence remains preliminary."},{"rthcId":"RPEP-12544","title":"Targeted nanoliposomal nutrient delivery for human health.","authors":"Mercola, Joseph","year":2025,"journal":"World journal of gastrointestinal pharmacology and therapeutics, 16(4), 111502","doi":"10.4292/wjgpt.v16.i4.111502","pmid":"41378075","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12545","title":"Vasoactive intestinal peptide induces metabolic rewiring of human-derived cytotrophoblast cells to promote cell migration.","authors":"Merech, Fátima; Lara, Brenda; Rios, Daiana; Paparini, Daniel; Ramhorst, Rosanna; Hauk, Vanesa; Pérez Leirós, Claudia; Vota, Daiana","year":2025,"journal":"Biochimica et biophysica acta. Molecular cell research, 1872(2), 119886","doi":"10.1016/j.bbamcr.2024.119886","pmid":"39653085","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12546","title":"GLP-1 receptor agonist for weight loss and fertility: Social media and online perception versus evidence-based medicine.","authors":"Merhi, Zaher; Karekar, Manasi; Mouanness, Marco","year":2025,"journal":"PloS one, 20(7), e0326210","doi":"10.1371/journal.pone.0326210","pmid":"40601607","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12547","title":"Impact of dramatic weight loss with the new injectable medications on reproduction in healthy non-polycystic ovary syndrome obese women.","authors":"Merhi, Zaher","year":2025,"journal":"F&S reports, 6(1), 4-9","doi":"10.1016/j.xfre.2024.12.003","pmid":"40201092","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Animal studies revealed contradictory GLP-1 effects on female reproduction:\n\nStimulatory effects (intracerebroventricular GLP-1):\n• Increased luteinizing hormone surge amplitude\n• Increased FSH secretion\n• Elevated serum progesterone\n• Up-regulated Kiss-1r expression in hypothalamus\n• Increased ovarian Graafian follicles and corpora lutea\n\nInhibitory effects (GLP-1 RA drugs):\n• Intracerebroventricular Exendin-4 and subcutaneous liraglutide produced opposite effects to native GLP-1\n• GLP-1 suppressed FSH-induced progesterone synthesis in granulosa cells despite up-regulating FSH receptor expression\n\nUterine effects (controversial):\n• Some studies: beneficial antifibrotic effect, reducing collagen deposition in intrauterine adhesion models\n• Other studies: destruction of luminal epithelium and shrinkage of muscle fibers","whyItMatters":"This is potentially one of the most important unanswered safety questions about GLP-1 drugs. Millions of reproductive-aged women without PCOS are using these medications for weight loss, but virtually all reproductive research has focused on women with PCOS. The contradictory animal data — where native GLP-1 stimulates reproduction but GLP-1 agonist drugs suppress it — is concerning and demands human studies before we can reassure women about fertility safety.","specificNumbers":"","methodology":"Narrative review critically analyzing published data on GLP-1 receptor agonists in non-PCOS females, covering both human and animal studies. The review focuses on effects on the hypothalamic-pituitary-ovarian (HPO) axis and uterine function.","limitations":"Most evidence is from animal models with different species, doses, routes, and GLP-1 agonists, making comparison difficult. Human data in non-PCOS women are essentially absent. The review acknowledges that animal findings are contentious and may not translate to humans. Intracerebroventricular drug delivery in animals doesn't replicate subcutaneous injection in humans. The specific GLP-1 drugs and doses causing different effects are not fully reconciled."},{"rthcId":"RPEP-12548","title":"Impact of the injectable weight-loss medications, glucagon-like peptide-1 receptor agonists, on reproductive health in non-polycystic ovary syndrome state.","authors":"Merhi, Zaher","year":2025,"journal":"Current opinion in obstetrics & gynecology, 37(4), 175-181","doi":"10.1097/GCO.0000000000001044","pmid":"40459435","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In animal models, GLP-1 receptor agonists caused lower ovarian weights, increased follicular atresia (egg cell death), and reduced serum steroid levels. They also downregulated kiss-1 and kiss-1r expression in the hypothalamus, leading to lower luteinizing hormone levels and delayed puberty. In the uterus, these drugs negatively affected the epithelial lining, though they reduced fibrosis in an intrauterine adhesion model. No human studies on fertility outcomes in non-PCOS women have been published to date.","whyItMatters":"Millions of reproductive-aged women without PCOS are now using GLP-1 receptor agonists for weight loss. The absence of human fertility data for this population represents a significant knowledge gap, and the concerning animal findings highlight the urgent need for clinical research before widespread long-term use.","specificNumbers":"","methodology":"This was a narrative review that critically analyzed existing animal studies using different GLP-1 receptor agonists (liraglutide, exendin-4, dulaglutide) in rats and mice, administered via subcutaneous or intracerebral routes at varying doses and durations.","limitations":"All reproductive findings come from animal models, which may not directly translate to humans. The animal studies used heterogeneous methods — different species, drug types, routes, and dosing protocols — making direct comparisons difficult. There are no prospective human clinical trials examining fertility endpoints in non-PCOS women taking GLP-1 RAs."},{"rthcId":"RPEP-12549","title":"The GLP-1 analog, exendin-4, improves bone material properties and strength through a central relay in ovariectomized mice.","authors":"Mermet, Morgane; Denom, Jessica; Mieczkowska, Aleksandra; Wery, Méline; Biggs, Emma; Gribble, Fiona M; Reimann, Frank; Magnan, Christophe; Cruciani-Guglielmacci, Céline; Mabilleau, Guillaume","year":2025,"journal":"American journal of physiology. Endocrinology and metabolism, 329(4), E522-E536","doi":"10.1152/ajpendo.00086.2025","pmid":"40789661","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12550","title":"Real-World Evidence of the Effect of Adjunctive Semaglutide on Weight Change, Glycemic Control, and Metabolic Dysfunction-Associated Steatotic Liver Disease in People with Type 1 Diabetes.","authors":"Mertens, Jonathan; De Winter, Hennah T; Dirinck, Eveline; Francque, Sven; De Block, Christophe","year":2025,"journal":"Diabetes technology & therapeutics","doi":"10.1177/15209156251362497","pmid":"40712645","tags":[],"studyType":"Observational / Real-World Study","evidenceStrength":"moderate","keyFinding":"In 42 overweight/obese adults with type 1 diabetes, once-weekly semaglutide produced a mean relative weight loss of 13.3% over 12 months — comparable to results seen in type 2 diabetes and obesity trials. Glycemic control also improved, and the proportion of patients with significant liver stiffness (>8 kPa, suggesting liver scarring) dropped dramatically from 20.6% to just 4.5%.\n\nTotal daily insulin requirements decreased by 13.6%, suggesting that semaglutide reduces insulin resistance even in the type 1 diabetes setting where insulin production is absent. Eight of 42 patients (19%) discontinued treatment, mainly due to gastrointestinal intolerance. The study provides the first substantial real-world evidence that semaglutide is safe and effective in type 1 diabetes, a population for which it is not currently approved.","whyItMatters":"Semaglutide is not approved for type 1 diabetes, and there are very few clinical studies in this population. Yet obesity is increasingly common among T1D patients, contributing to insulin resistance and fatty liver disease. This real-world study suggests semaglutide could benefit T1D patients in the same ways it helps T2D patients — weight loss, better glucose control, and liver improvement — potentially opening the door to formal clinical trials and eventual approval.","specificNumbers":"n=42 · 76.2% with obesity · 13.3% mean weight loss · 13.6% insulin dose reduction · Liver stiffness >8 kPa: 20.6% → 4.5% · 12-month follow-up · 19% discontinuation rate","methodology":"Real-world observational study of 42 overweight/obese adults with type 1 diabetes treated with once-weekly semaglutide for 12 months. Inclusion required stable glycemic control at baseline. Outcomes included weight change, HbA1c, total daily insulin dose, and liver stiffness measured by FibroScan (in 28 patients). Published in Diabetes Technology & Therapeutics.","limitations":"Small sample size (n=42) without a control group — the real-world design means there's no placebo comparison. The 19% discontinuation rate suggests tolerability issues in a subset of patients. Liver stiffness was only measured in 28 of 42 patients. Without randomization, selection bias may have favored patients more likely to respond well. Off-label use may not reflect how the drug would perform in a broader T1D population."},{"rthcId":"RPEP-12551","title":"Efficacy and Safety of Glucagon-Like Peptide-1 Agonists for Psychiatric Symptoms: A Systematic Review.","authors":"Meshkat, Shakila; Di Luciano, Corinna; Swiderski, Alyssa; Li, Gloria; Aguilar, Reinhard Janssen; Dunkley, Benjamin T; Reichelt, Amy C; Zhang, Yanbo; Greenshaw, Andrew; Vermetten, Eric; Jetly, Rakesh; Dash, Satya; Agarwal, Sri Mahavir; Swainson, Jennifer; Bhat, Venkat","year":2025,"journal":"Brain and behavior, 15(7), e70661","doi":"10.1002/brb3.70661","pmid":"40635383","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 26 studies (n=3,020), 5 evaluated psychiatric symptoms as primary outcomes and 21 as secondary outcomes:\n\nPrimary psychiatric outcomes: Exenatide 2 mg weekly reduced cocaine craving in a case series but showed no significant change in a separate study (n=12, p=0.46). Dulaglutide 1.5 mg weekly did not significantly affect smoking cessation (RR=0.87, p=0.25) but reduced alcohol consumption by 29% in a secondary analysis.\n\nSecondary psychiatric outcomes: Liraglutide 1.8 mg/day significantly improved depression and anhedonia. Semaglutide improved diabetes-related quality of life and anxiety (Cohen's d=0.48) compared to dulaglutide. Exenatide showed mixed results, with one RCT finding significant BDI score reduction (Δ=-5.2).\n\nOverall: Only 3 of 9 included RCTs reported significant effects on primary psychiatric outcomes; 6 reported null findings.","whyItMatters":"Millions of people now take GLP-1 drugs, and there is enormous public interest in their potential psychiatric benefits — especially for addiction and depression. This systematic review provides the most comprehensive assessment to date, tempering the hype with evidence. While some signals are promising, the mixed results highlight that GLP-1 drugs are not yet proven psychiatric treatments and more rigorous research is needed.","specificNumbers":"","methodology":"Systematic review searching OVID databases from inception to November 2024. 26 studies (n=3,020) were included, categorized by whether psychiatric outcomes were primary or secondary. 10 registered clinical trials were also identified. Risk of bias for the 9 included RCTs was assessed using the JBI Critical Appraisal Checklist, with all meeting majority of criteria indicating moderate-to-high methodological quality.","limitations":"The included studies were heterogeneous in design, GLP-1RA type, dosing, psychiatric outcomes measured, and patient populations. Most psychiatric outcomes were assessed as secondary endpoints, not primary. The number of studies with primary psychiatric outcomes was very small (5). Case series and observational studies constitute much of the evidence. Publication bias may favor positive findings. The review could not perform meta-analysis due to study heterogeneity."},{"rthcId":"RPEP-12552","title":"Efficacy and safety of GLP-1 agonists in Parkinson's disease: a systematic review and meta-analysis of randomized controlled trials.","authors":"Messak, Mark; Abdelmageed, Ahmed; Senbel, Abdelrahman A; Khattab, Youssef A; Mandour, Youssef; Shaker, Omar; Rehan, Ahmed Hamed; Oransa, Samir; Nasr, Mohamed; Shabeeb, Abdullah Emad; Rezq, Ziyad; Hossam, Fares; Abouelmagd, Moaz Elsayed","year":2025,"journal":"Naunyn-Schmiedeberg's archives of pharmacology, 398(8), 9721-9736","doi":"10.1007/s00210-025-03932-3","pmid":"40067438","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across four RCTs with 514 Parkinson's patients testing three different GLP-1 agonists:\n\n- Motor function (OFF-medication state): Significantly improved (MD = -3.29, 95% CI -5.17 to -1.42, p=0.0006)\n- Quality of life (PDQ-39): No significant improvement (MD = -0.54, 95% CI -2.07 to 0.99, p=0.49)\n- Adverse effects significantly higher in GLP-1 group: nausea (RR 1.98, p=0.0008), vomiting (RR 6.65, p=0.0008), constipation (RR 1.45, p=0.01), and weight loss (RR 2.11, p=0.03)\n- No other adverse effects were significantly increased","whyItMatters":"Current Parkinson's drugs mainly replace dopamine but don't slow disease progression. GLP-1 drugs may offer neuroprotective benefits that go beyond symptom management. The significant improvement in OFF-state motor function suggests these drugs could help during the periods when patients struggle most, potentially representing a new class of Parkinson's therapy.","specificNumbers":"","methodology":"Systematic review and meta-analysis of randomized controlled trials from PubMed, Scopus, Web of Science, OVID, Cochrane Central, and Google Scholar. Four RCTs met inclusion criteria, testing three different GLP-1 agonist formulations in 514 PD patients total. Quality assessed using Risk of Bias-2 domains. Statistical analysis calculated mean differences and risk ratios with 95% confidence intervals.","limitations":"Only four RCTs were available for analysis, with a total of 514 patients — relatively small for a meta-analysis. The trials tested different GLP-1 agonists, introducing heterogeneity. Quality of life did not significantly improve despite motor function gains. GI side effects (especially vomiting, RR 6.65) are a practical concern. The studies may have been too short to detect disease-modifying effects versus symptomatic improvement."},{"rthcId":"RPEP-12553","title":"An ovary-intact postmenopausal HFpEF mouse model; menopause is more than just estrogen deficiency.","authors":"Methawasin, Mei; Strom, Joshua; Marino, Vito A; Gohlke, Jochen; Muldoon, Julia; Herrick, Shelby R; van der Pijl, Robbert; Konhilas, John P; Granzier, Henk","year":2025,"journal":"American journal of physiology. Heart and circulatory physiology, 328(4), H719-H733","doi":"10.1152/ajpheart.00575.2024","pmid":"39963865","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12554","title":"Utilization and Outcomes of Glucagon-Like Peptide-1 Receptor Agonists in Posttransplant Diabetes Mellitus in Kidney Transplant Recipients.","authors":"Metoyer, Garyn; Whiteson, Harriz Z; Chen, Yusi; Li, Yiting; Gao, Chenxi; Menon, Gayathri; Bae, Sunjae; Lentine, Krista L; Segev, Dorry L; McAdams-DeMarco, Mara A; Orandi, Babak J","year":2025,"journal":"Clinical transplantation, 39(10), e70354","doi":"10.1111/ctr.70354","pmid":"41123471","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12555","title":"Discrimination of Oxytocin, a Behavioral Neuropeptide Hormone, and Its Structural Variants by Nanopore.","authors":"Meyer, Nathan; Ratinho, Laura; Greive, Sandra J; Bacri, Laurent; Thiebot, Bénédicte; Morozzo Della Rocca, Blasco; Chinappi, Mauro; Pelta, Juan; Cressiot, Benjamin","year":2025,"journal":"ACS nano, 19(31), 28690-28701","doi":"10.1021/acsnano.5c08031","pmid":"40730515","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12556","title":"Liraglutide for adults living with obesity.","authors":"Meza, Nicolás; Bracchiglione, Javier; Escobar Liquitay, Camila Micaela; Madrid, Eva; Varela, Lucia B; Guo, Yang; Urrútia, Gerard; Er, Selcuk; Tiller, Sandra; Shokraee, Kamyar; Alvarez Busco, Felipe; Solà, Ivan; Ocara Vargas, Miranda; Novik A, Victoria; Poloni, Daniel; Franco, Juan Va","year":2025,"journal":"The Cochrane database of systematic reviews, 10(10), CD016017","doi":"10.1002/14651858.CD016017","pmid":"41161684","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12557","title":"Tirzepatide retention in iWAT with mesoporous polydopamine encapsulation enhances weight loss through leptin receptor signaling.","authors":"Mi, Lin; Li, Tan; Xiang, Xiaoxin; Zhou, Yimin; Xiong, Na; Chen, Yanyu; Chen, Jiaoting; Shang, Sijia; Chen, Shumeng; Cheung, Wai W; Xiao, Zecong; Chen, Yanming; Wang, Jiahai; Peng, Jun; Shuai, Xintao; Shi, Guojun","year":2025,"journal":"Journal of advanced research","doi":"10.1016/j.jare.2025.09.009","pmid":"40945849","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12558","title":"Evolutionary dynamics and regulatory site analysis of AMP family genes in cattle and sheep.","authors":"Mi, Xiaoyu; Wu, Lingyun; Song, Yanliang; Wang, Xiaoyan; Zhu, Zhenliang; Zhao, Jianglin; Su, Jie; Xue, Jiaoxiong; Lin, Benteng; Gao, Dandan; Wang, Fei; Feng, Rui; Gao, Yuanpeng; Liu, Jun; Zhang, Yong","year":2025,"journal":"International journal of biological macromolecules, 290, 138922","doi":"10.1016/j.ijbiomac.2024.138922","pmid":"39708887","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12559","title":"Application of machine learning in the discovery of antimicrobial peptides: exploring their potential for ulcerative colitis therapy.","authors":"Miao, Hui; Wang, Ziwei; Chen, Shihu; Wang, Jiaqi; Ma, Hongyue; Liu, Yifan; Yang, Hui; Guo, Ziyi; Wang, Jiamei; Cui, Pengfei","year":2025,"journal":"eGastroenterology, 3(4), e100253","doi":"10.1136/egastro-2025-100253","pmid":"41477025","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12560","title":"Managing cardiovascular events, hyperglycemia, and obesity in type 2 diabetes through microRNA regulation linked to glucagon-like peptide-1 receptor agonists.","authors":"Miao, Xiaolei; Davoudi, Maryam; Alitotonchi, Zahra; Ahmadi, Ensieh Sadat; Amraee, Fatemeh; Alemi, Ashraf; Afrisham, Reza","year":2025,"journal":"Diabetology & metabolic syndrome, 17(1), 13","doi":"10.1186/s13098-025-01581-3","pmid":"39794819","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12561","title":"Impact of Semaglutide 2.4 mg on Healthcare Resource Utilization and Medical Costs in Patients With Heart Failure in the United States (SHINE-HF).","authors":"Michalak, Wojciech; Zhao, Zhenxiang; Faurby, Mads; Alvarez, Sara; Fitch, Angela","year":2025,"journal":"Clinical therapeutics, 47(10), 875-883","doi":"10.1016/j.clinthera.2025.07.018","pmid":"40813184","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12562","title":"Impact of semaglutide 2.4 mg on healthcare resource utilization and medical costs in patients with atherosclerotic cardiovascular disease in the United States (SHINE-ASCVD).","authors":"Michalak, Wojciech; Zhao, Zhenxiang; Faurby, Mads; Alvarez, Sara; Fitch, Angela","year":2025,"journal":"Journal of medical economics, 28(1), 1075-1085","doi":"10.1080/13696998.2025.2526282","pmid":"40579810","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12563","title":"Missed Doses, Missed Opportunities: Readmission Due to GLP-1RA Interruption Inspires Algorithms to Improve Reinitiation of Therapy at Discharge.","authors":"Michelet, Adrienne; Mowla, Maksudul; Amo-Brown, Baaba A; Rodriguez, Natalie; Cavaretta, Marissa","year":2025,"journal":"Hospital pharmacy, 00185787251372054","doi":"10.1177/00185787251372054","pmid":"41017792","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12564","title":"The impact of GLP-1 agonists on sleep disorders: spotlight on sleep apnea.","authors":"Mifsud, Caroline S; Kolla, Bhanu Prakash; Rushlow, David R; Mansukhani, Meghna P","year":2025,"journal":"Expert opinion on pharmacotherapy, 26(14-15), 1529-1538","doi":"10.1080/14656566.2025.2574848","pmid":"41114602","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12565","title":"Short Peptides as Excipients in Parenteral Protein Formulations: A Mini Review.","authors":"Migoń, Dorian; Jaremicz, Zbigniew; Kamysz, Wojciech","year":2025,"journal":"Pharmaceutics, 17(10)","doi":"10.3390/pharmaceutics17101328","pmid":"41155963","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12566","title":"Secondary stroke prevention beyond antiplatelets: The role of colchicine and GLP-1RA - an ounce of prevention is worth a pound of cure.","authors":"Mijajlović, Milija D; Bornstein, Natan M; Aleksić, Vuk","year":2025,"journal":"Therapeutic advances in neurological disorders, 18, 17562864251326769","doi":"10.1177/17562864251326769","pmid":"40291758","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12567","title":"Carnitine Deficiency Caused by Salcaprozic Acid Sodium Contained in Oral Semaglutide in a Patient with Multiple Acyl-CoA Dehydrogenase Deficiency.","authors":"Mikami-Saito, Yasuko; Maekawa, Masamitsu; Watanabe, Masahiro; Hosaka, Shinichiro; Takahashi, Kei; Totsune, Eriko; Arai-Ichinoi, Natsuko; Kikuchi, Atsuo; Kure, Shigeo; Katagiri, Hideki; Wada, Yoichi","year":2025,"journal":"International journal of molecular sciences, 26(7)","doi":"10.3390/ijms26072962","pmid":"40243535","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12568","title":"Treatment of obesity with GLP-1 receptor agonist after bariatric surgery: Real-world evidence.","authors":"Milad, Camila; Logwin, Sergio; Antón, Nerea; Jiménez, Amanda; Flores, Lilliam; Ibarzábal, Ainitze; Moizé, Violeta; Pané, Adriana; Vidal, Josep; de Hollanda, Ana","year":2025,"journal":"Medicina clinica, 165(4), 107153","doi":"10.1016/j.medcli.2025.107153","pmid":"40865274","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12569","title":"Genome-Wide Translatome Analysis Following Low-Dose Ketamine to Reveal Novel Targets for Antidepressant Treatment.","authors":"Miller, Oliver H; Grabole, Nils; Wells, Isabelle; Bellier, Ludovic; Nassi, Jonathan J; Hall, Benjamin J","year":2025,"journal":"Synapse (New York, N.Y.), 79(6), e70033","doi":"10.1002/syn.70033","pmid":"41254482","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Using ribosome profiling (RiboSeq) to capture the complete set of actively translated proteins in the medial prefrontal cortex after antidepressant-dose ketamine, researchers identified VPAC2 — the receptor for the neuropeptide vasoactive intestinal peptide (VIP) — as a novel target for antidepressant action.\n\nVPAC2 expression in the prefrontal cortex was found to be limited to somatostatin-positive inhibitory neurons. When a VPAC2 agonist was administered in vivo, it bidirectionally modulated pyramidal neuron activity and disrupted coordinated neural activity patterns. Critically, VPAC2 agonism alone was sufficient to drive an antidepressant response in mice, validating this neuropeptide receptor as a potential drug target independent of ketamine itself.","whyItMatters":"Depression affects hundreds of millions of people worldwide, and many patients don't respond to standard antidepressants. Ketamine works fast but has practical limitations including its dissociative effects. Identifying that a specific neuropeptide receptor — VPAC2 — can independently produce antidepressant effects opens the door to developing targeted peptide-based or small-molecule antidepressants that could work through this pathway without ketamine's side effects.","specificNumbers":"","methodology":"Researchers administered an antidepressant-like dose of ketamine to mice and then used ribosome-bound mRNA footprinting with deep sequencing (RiboSeq) to identify all actively translated mRNAs in the medial prefrontal cortex — creating a genome-wide 'translatome' map. They used Gene Ontology and Gene Set Enrichment Analysis to identify key pathways. They then characterized the VPAC2 receptor's location and function in the cortex, tested a VPAC2 agonist's effects on prefrontal cortical neuron activity in vivo, and assessed whether VPAC2 agonism produced antidepressant-like behavioral effects.","limitations":"This was entirely a mouse study, and antidepressant-like behavior in mice does not always predict human clinical responses. The specific VPAC2 agonist used and its dosing were not detailed in the abstract. The study focused on the medial prefrontal cortex, but depression involves multiple brain regions. Long-term effects of VPAC2 agonism and potential side effects were not assessed."},{"rthcId":"RPEP-12570","title":"Predictive factors for HbA1c and weight loss associated with semaglutide treatment in type 2 diabetes mellitus: real-world clinical evidence.","authors":"Milushewa, Petya; Mitreva, Yoanna; Chakarova, Nevena; Tankova, Tsvetalina; Naseva, Emilia; Petkova, Valentina","year":2025,"journal":"Frontiers in endocrinology, 16, 1621892","doi":"10.3389/fendo.2025.1621892","pmid":"41036135","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"After one year of subcutaneous semaglutide treatment (titrated from 0.25 mg to 1 mg weekly), 168 type 2 diabetes patients showed significant improvements across all measured metabolic parameters. Median weight decreased from 100.0 kg to 91.5 kg (p<0.001), median BMI from 33.6 to 30.9 kg/m² (p<0.001), and HbA1c from 7.80% to 6.90% (p<0.001).\n\nAt baseline, 92.3% of patients had obesity (BMI ≥30), with 53.6% in Obesity Class 1. After treatment, 81 patients transitioned to lower obesity classes, though 15 remained in Class 3 obesity.","whyItMatters":"Clinical trials show semaglutide works well under controlled conditions, but real-world data from routine practice is essential to confirm those benefits hold up. This Bulgarian study adds to the growing body of evidence that semaglutide delivers meaningful weight loss and blood sugar improvements in everyday clinical settings, including in Eastern European healthcare systems where access patterns may differ.","specificNumbers":"","methodology":"Retrospective analysis of 168 type 2 diabetes patients receiving dispensary monitoring at a specialized endocrinology hospital in Sofia, Bulgaria. Clinical data including comorbidities, HbA1c, weight, and BMI were collected from medical records at baseline and after one year. Patients followed a standard titration protocol: 0.25 mg weekly for four weeks, then 0.5 mg, then 1 mg maintained for the remainder of the year.","limitations":"This was a retrospective study without a control group, making it impossible to separate semaglutide's effects from other interventions or natural progression. The study was conducted at a single specialized hospital, which may represent a more closely monitored population than typical practice. Only one year of follow-up was available, so long-term sustainability of results is unknown. The abstract does not report dropout rates or adverse events."},{"rthcId":"RPEP-12571","title":"Pregabalin as a Potential Adjunct in the Management of Pruritus in Prurigo Nodularis: A Case Report.","authors":"Mima, Yoshihito; Yamamoto, Masako; Iozumi, Ken","year":2025,"journal":"Cureus, 17(7), e88297","doi":"10.7759/cureus.88297","pmid":"40837911","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A 69-year-old woman with prurigo nodularis achieved complete skin lesion resolution with nemolizumab. Discontinuation of pregabalin (prescribed for coexisting sciatic pain) led to pruritus recurrence within 2 months despite continued absence of visible lesions. Reintroduction of low-dose pregabalin stabilized symptoms within 2 months. The proposed mechanism is pregabalin's inhibition of α2δ voltage-gated calcium channel subunits, suppressing release of excitatory neuropeptides including substance P and CGRP.","whyItMatters":"Prurigo nodularis causes debilitating itch that severely impacts quality of life. While new biologics like nemolizumab clear skin lesions, some patients continue to experience neuropathic itch. Understanding that pregabalin may address this residual itch through neuropeptide suppression could provide an affordable adjunctive treatment, especially since pregabalin is already widely available and inexpensive as a generic.","specificNumbers":"","methodology":"Single-patient case report documenting the temporal relationship between pregabalin use/discontinuation/reintroduction and pruritus control in a patient with prurigo nodularis concurrently treated with nemolizumab.","limitations":"This is a single case report, the lowest level of clinical evidence. The temporal association between pregabalin and itch control is suggestive but cannot prove causation. The patient was concurrently on nemolizumab, making it difficult to fully attribute effects to pregabalin. Placebo effects cannot be excluded. No itch severity scoring was reported."},{"rthcId":"RPEP-12572","title":"Association Between Early Weight Loss and Metabolic Outcomes with Tirzepatide in Japanese Patients with Type 2 Diabetes: A SURPASS J Post Hoc Analysis.","authors":"Mimura, Hanaka; Oura, Tomonori; Chin, Rina; Hirase, Tetsuaki; Shimono, Dai","year":2025,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 16(9), 1871-1885","doi":"10.1007/s13300-025-01775-y","pmid":"40711720","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12573","title":"Association of bodyweight loss with changes in lipids, blood pressure, and fasting serum glucose following tirzepatide treatment in Japanese participants with type 2 diabetes: A post hoc analysis of the SURPASS J-mono trial.","authors":"Mimura, Hanaka; Oura, Tomonori; Chin, Rina; Takeuchi, Masakazu; Fujihara, Kazuya; Sone, Hirohito","year":2025,"journal":"Journal of diabetes investigation, 16(5), 807-816","doi":"10.1111/jdi.14395","pmid":"39891527","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12574","title":"A Comprehensive Review on the Pharmacokinetics and Drug-Drug Interactions of Approved GLP-1 Receptor Agonists and a Dual GLP-1/GIP Receptor Agonist.","authors":"Min, Jee Sun; Jo, Seong Jun; Lee, Sangyoung; Kim, Duk Yeon; Kim, Da Hyun; Lee, Chae Bin; Bae, Soo Kyung","year":2025,"journal":"Drug design, development and therapy, 19, 3509-3537","doi":"10.2147/DDDT.S506957","pmid":"40330819","tags":["glp-1-agonists","pharmacokinetics","drug-interactions"],"studyType":"Review","evidenceStrength":"Strong","keyFinding":"This comprehensive review maps the pharmacokinetics and drug interactions of all approved GLP-1 receptor agonists (exenatide, liraglutide, dulaglutide, semaglutide) plus tirzepatide (the dual GLP-1/GIP agonist). Native GLP-1 has a half-life of just 2 minutes — the structural modifications that extend this (amino acid substitutions, fatty acid conjugation, albumin binding, Fc fusion) vary by drug and produce dramatically different pharmacokinetic profiles.\n\nThe review finds that most drug-drug interactions (DDIs) with GLP-1 RAs are clinically insignificant — they don't interfere with liver enzymes or drug transporters. The main DDI mechanism is delayed gastric emptying, which slows absorption of co-administered oral drugs. However, two notable exceptions require monitoring: tirzepatide significantly altered oral contraceptive exposure, and oral semaglutide affected levothyroxine levels. Additionally, GLP-1 drug-induced changes in body fat, kidney filtration, and liver enzyme activity could affect other drugs in ways not yet well understood.","whyItMatters":"Millions of people now take GLP-1 drugs alongside other medications. Understanding drug interactions is critical for patient safety — especially for oral contraceptives (failure could mean unintended pregnancy) and thyroid medication (under-dosing could cause hypothyroid symptoms). This review provides the most comprehensive pharmacokinetic comparison of all approved GLP-1/GIP drugs in one place, making it an essential reference for prescribers managing patients on multiple medications.","specificNumbers":"5 drugs reviewed · native GLP-1 half-life: 2 min · DDI concerns: oral contraceptives (tirzepatide) + levothyroxine (oral semaglutide) · 30 PK models developed · delayed gastric emptying = main DDI mechanism","methodology":"Comprehensive narrative review synthesizing pharmacokinetic data, drug interaction studies, and pharmacokinetic modeling approaches for all approved GLP-1 RAs and tirzepatide. Covers structural modifications, metabolism, renal excretion, and both enzyme/transporter-mediated and mechanism-of-action-mediated drug interactions.","limitations":"As a narrative review, it synthesizes existing data rather than generating new findings. Many potential DDIs (especially those mediated by body composition changes or altered CYP activity) remain poorly studied. The review focuses on approved drugs and may not cover investigational GLP-1 compounds. Individual patient variability in pharmacokinetics is acknowledged but not modeled. Post-marketing DDI data may be limited for newer drugs like tirzepatide."},{"rthcId":"RPEP-12575","title":"Galectin-3 as a prognostic biomarker in haemodialysis patients with preserved or mildly reduced ejection fraction.","authors":"Min, Sei Hong; Kim, Insoo; An, Jung Nam; Lee, Hyung-Seok; Kim, Sung Gyun; Kim, Jwa-Kyung","year":2025,"journal":"Clinical kidney journal, 18(10), sfaf306","doi":"10.1093/ckj/sfaf306","pmid":"41158187","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12576","title":"2023 Update of the Japanese Heart Failure Society Scientific Statement on BNP and NT-proBNP Levels in Heart Failure Practice.","authors":"Minamisawa, Masatoshi; Anzai, Toshihisa; Inomata, Takayuki; Kinugawa, Koichiro; Sakata, Yasushi; Sato, Naoki; Tsutsui, Hiroyuki; Yamamoto, Kazuhiro; Yoshimura, Michihiro; Saito, Yoshihiko; Kuwahara, Koichiro","year":2025,"journal":"Journal of cardiac failure, 31(9), 1453-1459","doi":"10.1016/j.cardfail.2025.03.005","pmid":"40120714","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12577","title":"Ethical Issues Related to the Use of GLP-1 Receptor Agonists Such as Ozempic and Mounjaro: Impact on Individuals and Society at Large.","authors":"Minerva, Francesca","year":2025,"journal":"Bioethics","doi":"10.1111/bioe.70068","pmid":"41353657","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12578","title":"Subtype- and Site-Specific Innervation of Melanocytic Nevi as Revealed by PGP 9.5 and CGRP Expression.","authors":"Minigo, Bruno; Ogorevc, Marin; Kelam, Nela; Čizmić, Ante; Zekić Tomaš, Sandra; Vukojević, Katarina; Kostić, Sandra; Vuković, Dubravka; Mardešić, Snježana","year":2025,"journal":"Medicina (Kaunas, Lithuania), 61(10)","doi":"10.3390/medicina61101828","pmid":"41155815","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12579","title":"The Integration of Lifestyle Modification Advice and Diet and Physical Exercise Interventions: Cornerstones in the Management of Obesity with Incretin Mimetics.","authors":"Minnetti, Marianna; Barazzoni, Rocco; Batsis, John A; Busetto, Luca; Yumuk, Volkan; Poggiogalle, Eleonora; Weijs, Peter J M; Donini, Lorenzo M","year":2025,"journal":"Obesity facts, 1-16","doi":"10.1159/000548370","pmid":"41252315","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12580","title":"GLP-1 receptor agonists in the context of cancer: the road ahead.","authors":"Miousse, Isabelle R","year":2025,"journal":"American journal of physiology. Cell physiology, 328(6), C1822-C1828","doi":"10.1152/ajpcell.00245.2025","pmid":"40285503","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12581","title":"Exploring red blood cells as an antigen delivery system to modulate the immune response towards FVIII in hemophilia A.","authors":"Miranda, Mariarosaria; Brandsma, Eelke; Robben, Lotte; Van Dender, Helena; van Alphen, Floris P J; Fijnvandraat, Karin; van den Biggelaar, Maartje; Lacroix-Desmazes, Sebastien; van Bruggen, Robin; Voorberg, Jan","year":2025,"journal":"Journal of thrombosis and haemostasis : JTH, 23(3), 836-848","doi":"10.1016/j.jtha.2024.11.012","pmid":"39617188","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12582","title":"Impact of semaglutide on lipid profiles in overweight and obese non-diabetic adults: A systematic review and meta-analysis of randomized controlled trials.","authors":"Miranda, Sarah; Choudhari, Jashkumar; Chauhan, Nehabahen; Parmar, Mayur S","year":2025,"journal":"European journal of pharmacology, 1003, 177953","doi":"10.1016/j.ejphar.2025.177953","pmid":"40675357","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12583","title":"Comparing the wound healing properties of two antibacterial peptides, CM11 and FR7, using a rat model with an infected wound.","authors":"Mirnejad, Reza; Heydari, Hamid; Moosazadeh Moghaddam, Mehrdad; Fasihi-Ramandi, Mahdi; Izadi, Morteza; Hosseini, Zahra Sadat; Golmohammadi, Reza","year":2025,"journal":"Biochemical and biophysical research communications, 791, 152930","doi":"10.1016/j.bbrc.2025.152930","pmid":"41232384","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12584","title":"NMR Unveils Activity Mechanism of Linear Spider Venom Peptide Fragments Selected by Neural Networks Against Staphylococci Including MRSA.","authors":"Mironov, Pavel A; Baranova, Anna A; Alferova, Vera A; Egorova, Natalya S; Ignatova, Anastasia A; Feofanov, Alexey V; Shenkarev, Zakhar O; Dubovskii, Peter V","year":2025,"journal":"Pharmaceutics, 17(12)","doi":"10.3390/pharmaceutics17121526","pmid":"41471040","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12585","title":"Atezolizumab and Bevacizumab Induced Diabetes Mellitus and Myocarditis: A Case Report.","authors":"Mirza, Muhammad A; Periyasami, Vimalraj; Kasi, Amail; Pampapathi, Keerthana; Sagi, Satyanarayana V","year":2025,"journal":"Cureus, 17(11), e97311","doi":"10.7759/cureus.97311","pmid":"41426882","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12586","title":"Tirzepatide mitigates cognitive decline in zebrafish model of type 2 diabetes mellitus induced by high-fat diet.","authors":"Misra, Sakshi; Rajput, Prabha; Kaur, Amandeep","year":2025,"journal":"Naunyn-Schmiedeberg's archives of pharmacology, 398(7), 8861-8883","doi":"10.1007/s00210-025-03827-3","pmid":"39873719","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12587","title":"Efficacy and safety of retatrutide for the treatment of obesity: a systematic review of clinical trials.","authors":"Misra, Saurav; Narayan, Ravi Kant; Kaur, Manmeet","year":2025,"journal":"Journal of basic and clinical physiology and pharmacology, 36(4), 263-274","doi":"10.1515/jbcpp-2025-0113","pmid":"40728138","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across three clinical trials screening 1,082 patients (691 randomized: 510 retatrutide, 130 placebo), the 12 mg weekly dose produced the most significant results:\n\n• Greatest reductions in body weight, BMI, and waist circumference across all dose groups\n• Higher proportion of patients achieving weight loss thresholds of ≥5%, ≥10%, ≥15%, and ≥20%\n• Significant metabolic improvements compared to placebo\n• Gastrointestinal adverse effects were the most commonly reported side effects\n\nThe study population averaged 54.26 years of age with a near-equal gender split (48% men, 52% women).","whyItMatters":"While GLP-1 agonists (semaglutide) and dual agonists (tirzepatide) have already transformed obesity treatment, retatrutide's triple-receptor approach could push weight loss even further. Adding glucagon receptor activation to GLP-1 and GIP signaling may enhance energy expenditure and fat burning beyond what dual agonists achieve, potentially bringing pharmaceutical weight loss closer to bariatric surgery results.","specificNumbers":"","methodology":"Systematic review following PRISMA guidelines, searching PubMed, Cochrane, and ClinicalTrials.gov from inception through March 15, 2025. Three articles met inclusion criteria, encompassing clinical trials of retatrutide for obesity treatment. Data were extracted on efficacy (weight loss, BMI change, waist circumference) and safety (adverse events) outcomes.","limitations":"Only three clinical trials were available for inclusion, limiting the scope of evidence. The total randomized sample (691 patients) is relatively small for a systematic review. Long-term efficacy and safety data beyond the trial periods are not available. The review does not report specific weight loss percentages by dose group. Phase 3 trial results were not yet available at the time of this review."},{"rthcId":"RPEP-12588","title":"Usefulness of hypochloremia at the time of discharge to predict prognosis in patients with chronic heart failure after hospitalization.","authors":"Misumi, Kayo; Matsue, Yuya; Nogi, Kazutaka; Fujimoto, Yudai; Kagiyama, Nobuyuki; Kasai, Takatoshi; Kitai, Takeshi; Oishi, Shogo; Akiyama, Eiichi; Suzuki, Satoshi; Yamamoto, Masayoshi; Kida, Keisuke; Okumura, Takahiro; Nogi, Maki; Ishihara, Satomi; Ueda, Tomoya; Kawakami, Rika; Saito, Yoshihiko; Minamino, Tohru","year":2025,"journal":"Journal of cardiology, 85(3), 235-240","doi":"10.1016/j.jjcc.2024.08.011","pmid":"39222710","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12589","title":"Effect of Point Mutations on the Aggregation Tendency of the Antimicrobial Fragment Peptide hLL-3717-29.","authors":"Mitra, Aritra; Paul, Sandip","year":2025,"journal":"The journal of physical chemistry. B, 129(44), 11474-11489","doi":"10.1021/acs.jpcb.5c05943","pmid":"41147899","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"All-atom molecular dynamics simulations of the wild-type hLL-37₁₇₋₂₉ peptide and five I24 mutants revealed a biphasic aggregation process: rapid small oligomer formation via hydrophobic collapse, followed by structural reorganization.\n\nMutant-specific behaviors were striking: I24D (aspartate) and I24Q (glutamine) were strongly aggregation-prone, I24K (lysine) was aggregation-resistant with strong solvation and minimal clumping, and I24A (alanine) and I24S (serine) showed intermediate behavior. Mutations destabilized the amphipathic α-helix critical for membrane activity, especially charged variants, with helix unfolding concentrated near the peptide termini. Aggregate morphology remained predominantly fibrillar across all systems, but internal order varied. Aggregation was governed by a balance between electrostatic and van der Waals forces, with each mutation shifting this balance differently.","whyItMatters":"Antimicrobial peptides are being developed as alternatives to antibiotics, but designing effective versions requires understanding exactly how they work at the molecular level. Since LL-37's bacteria-killing ability depends on aggregation, knowing which amino acid changes enhance or reduce clumping provides a blueprint for engineering more potent antimicrobial peptides. This is especially valuable as antibiotic resistance continues to grow worldwide.","specificNumbers":"","methodology":"Researchers performed all-atom molecular dynamics (MD) simulations under constant pressure and temperature (NPT) conditions. They modeled the wild-type hLL-37₁₇₋₂₉ peptide and five point mutants (I24A, I24D, I24K, I24Q, I24S) in explicit solvent. They analyzed aggregation kinetics, secondary structure stability, transition network pathways, aggregate morphology, energetic contributions, preferential interaction parameters, and hydrogen bonding patterns to comprehensively characterize how each mutation altered aggregation behavior.","limitations":"This is a purely computational study using molecular dynamics simulations. While the simulations are detailed, they model peptide behavior in water rather than at actual bacterial membrane surfaces, where aggregation occurs in nature. The simulation timescales may not capture all relevant slow conformational changes. Experimental validation of the predicted aggregation behaviors has not been performed. The simulations focused on aggregation propensity but did not directly model antimicrobial activity."},{"rthcId":"RPEP-12590","title":"Secondary Cardiorenal Syndrome in a Cohort of Septic Patients Treated in a Medical Intensive Care Unit: A Single-Center Experience.","authors":"Mitrovic, Bojan C; Tomasevic, Ratko S; Mijuskovic, Svetozar R; Gluvic, Zoran M","year":2025,"journal":"Cureus, 17(10), e93639","doi":"10.7759/cureus.93639","pmid":"41185804","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12591","title":"Number Needed to Treat and Cost Per Responder Analysis of Anti-CGRP Monoclonal Antibodies for Migraine Prevention in Adults for Whom Prior Preventive Treatments have Failed.","authors":"Mitsikostas, Dimos D; Awad, Susanne F; Kongerslev, Rikke; Boserup, Line Pickering; Lee, Xin Ying; Phul, Ravinder; Sacco, Simona","year":2025,"journal":"Advances in therapy, 42(11), 5742-5760","doi":"10.1007/s12325-025-03348-8","pmid":"40986186","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12592","title":"Insects on the Plate: Nutritional Benefits, Health Impacts, and Market Dynamics.","authors":"Mittal, Ravi Kumar; Krishna, Gaurav; Chowdhury, Sohini; Lakhanpal, Sorabh; Shabil, Muhammed; Sharma, Rajeev; Suri, Sahil","year":2025,"journal":"Current protein & peptide science","doi":"10.2174/0113892037382429250624123540","pmid":"40660440","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12593","title":"Heart Failure Induced by Darolutamide in an Older Patient With M0 Castration-Resistant Prostate Cancer: A Case Report.","authors":"Miyaji, Yoshiyuki; Shimizu, Shinjiro; Sato, Michihiro","year":2025,"journal":"IJU case reports, 8(5), 466-469","doi":"10.1002/iju5.70068","pmid":"40909318","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12594","title":"Collagen Peptide Supplementation Enhances Muscle-Tendon Stiffness and Explosive Strength: A 16-wk Randomized Controlled Trial.","authors":"Miyamoto, Naokazu; Ishihara, Kaoru; Oshima, Toshiki; Kawai, Misae; Oritani, Yukihiro; Iemoto, Naoki","year":2025,"journal":"Medicine and science in sports and exercise, 57(12), 2877-2886","doi":"10.1249/MSS.0000000000003814","pmid":"40623147","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12595","title":"A cytotoxic peptide-drug conjugate for tumor-specific delivery of co-injected molecules.","authors":"Miyamura, Norio; Yamazaki, Chisato M; Anami, Yasuaki; Tsuchikama, Kyoji; Sugahara, Kazuki N","year":2025,"journal":"PloS one, 20(9), e0331564","doi":"10.1371/journal.pone.0331564","pmid":"40892758","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12596","title":"Deep learning-optimized multi-enzyme hydrolysis for walnut antihypertensive peptides.","authors":"Mo, Fan; Long, Rui; Shen, Yingbin; Xie, Qiang; Wang, Ping; Zhang, Liling; Jiang, Shuai; Yang, Xinquan; Jiang, Ling","year":2025,"journal":"International journal of biological macromolecules, 332(Pt 2), 148700","doi":"10.1016/j.ijbiomac.2025.148700","pmid":"41177473","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12597","title":"Comparative effectiveness of combining antidiabetic medications to treat renal impairment in patients with type 2 diabetes mellitus.","authors":"Mo, Qiu; Adam, Terrence J; Johnson, Steven G; Moheet, Amir; Pieczkiewicz, David S","year":2025,"journal":"Scientific reports, 15(1), 25735","doi":"10.1038/s41598-025-10299-1","pmid":"40670474","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12598","title":"GLP-1 and the Degenerating Brain: Exploring Mechanistic Insights and Therapeutic Potential.","authors":"Moaket, Osama Sobhi; Obaid, Sarah Eyad; Obaid, Fawaz Eyad; Shakeeb, Yusuf Abdulkarim; Elsharief, Samir Mohammed; Tania, Afrin; Darwish, Radwan; Butler, Alexandra E; Moin, Abu Saleh Md","year":2025,"journal":"International journal of molecular sciences, 26(21)","doi":"10.3390/ijms262110743","pmid":"41226780","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 receptor agonists show broad neuroprotective potential across multiple neurodegenerative diseases. In preclinical models, they reduce amyloid-β and tau pathology in Alzheimer's, preserve dopaminergic neurons in Parkinson's, protect brain cells after stroke, and alleviate depression. These effects are mediated through cAMP/PKA, PI3K/Akt, and MAPK signaling pathways that promote neuronal survival, reduce neuroinflammation, inhibit apoptosis, and enhance synaptic plasticity. Early clinical trials show attenuation of cortical atrophy and preserved brain glucose metabolism, though core AD biomarker changes remain inconclusive.","whyItMatters":"Neurodegenerative diseases affect hundreds of millions worldwide with few effective treatments. The discovery that GLP-1 — a gut peptide already targeted by blockbuster diabetes drugs — has potent neuroprotective effects could transform brain disease treatment. Since GLP-1 RAs like liraglutide and exenatide are already safe, widely available, and can cross the blood-brain barrier, repurposing them for Alzheimer's and Parkinson's could be faster and cheaper than developing entirely new drugs.","specificNumbers":"GLP-1R expressed in hippocampus, frontal cortex, substantia nigra · activates cAMP/PKA, PI3K/Akt, MAPK pathways · liraglutide, exenatide, dulaglutide cross BBB · ongoing trials: EVOKE, ELAD · covers AD, PD, stroke, depression","methodology":"This is a comprehensive review consolidating preclinical mechanistic studies, translational research, and early-phase clinical trial results on GLP-1 receptor agonists across Alzheimer's disease, Parkinson's disease, stroke, and depression.","limitations":"As a review, no new data are presented. While preclinical evidence is strong, clinical trial results for AD biomarkers remain inconclusive. The large-scale trials (EVOKE, ELAD) were ongoing at publication. Whether neuroprotective doses differ from metabolic doses is not established. The heterogeneity of neurodegenerative diseases makes it unclear which patient subpopulations would benefit most."},{"rthcId":"RPEP-12599","title":"Oppositely biased glucagon-like peptide-1 receptor agonism does not differentially affect lipid metabolism in APOE*3-Leiden CETP mice.","authors":"Modder, Melanie; Tomas, Alejandra; Afkir, Salwa; Pronk, Amanda C M; Streefland, Trea C M; Lalai, Reshma A; van Eenige, Robin; Rensen, Patrick C N; Jones, Ben; Kooijman, Sander","year":2025,"journal":"Diabetes, obesity & metabolism, 27(6), 3477-3489","doi":"10.1111/dom.16374","pmid":"40176480","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The G protein-biased agonist acyl-ExF1, when given peripherally for 6 weeks, prevented body weight gain and reduced plasma glucose levels, while the β-arrestin-biased agonist acyl-ExD3 did not. However, neither agonist significantly affected circulating lipid levels when given peripherally.\n\nIn contrast, when administered directly into the brain (intracerebroventricular infusion for 18 days), both agonists strongly reduced plasma triglyceride and cholesterol levels but did not affect glucose levels. Both increased fatty acid uptake by adipose tissue — acyl-ExD3 significantly in brown adipose tissue, acyl-ExF1 in white adipose tissue. The key finding is that signaling bias at the GLP-1 receptor does not differentially affect lipid metabolism.","whyItMatters":"Pharmaceutical companies are designing next-generation GLP-1 drugs that preferentially activate specific signaling pathways, hoping to separate beneficial effects from side effects. This study shows that while signaling bias matters for blood sugar and weight control, it doesn't make a difference for lipid metabolism — an important finding for drug design strategy.","specificNumbers":"","methodology":"Hyperlipidemic APOE*3-Leiden.CETP transgenic mice were treated with either saline, acyl-ExD3 (β-arrestin-biased), or acyl-ExF1 (G protein-biased) via intraperitoneal injection for 6 weeks or intracerebroventricular infusion for 18 days. Body weight, composition, and plasma levels of glucose, triglycerides, and cholesterol were monitored. At endpoint, labeled VLDL-like particles were used to track triglyceride-derived fatty acid uptake by brown and white adipose tissue.","limitations":"This is an animal study using transgenic mice, so results may not directly translate to humans. The two signaling bias profiles were compared using modified exendin-4 compounds, not clinically approved drugs. Central administration (directly into the brain) is not a viable clinical delivery route. The study duration was relatively short, and long-term lipid effects may differ."},{"rthcId":"RPEP-12600","title":"Dairy-Gut Microbiome Interactions: Implications for Immunity, Adverse Reactions to Food, Physical Performance and Cardiometabolic Health-A Narrative Review.","authors":"Modrego, Javier; Pantoja-Arévalo, Lisset; Gómez-Garre, Dulcenombre; Gesteiro, Eva; González-Gross, Marcela","year":2025,"journal":"Nutrients, 17(20)","doi":"10.3390/nu17203312","pmid":"41156563","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12601","title":"Association of tirzepatide with glycaemic control and weight loss in a real world cohort of patients with type 2 diabetes from the United States.","authors":"Mody, Reema; Desai, Karishma; Teng, Chia-Chen; Reznor, Gally; Stockbower, Grace; Grabner, Michael; Benneyworth, Brian D","year":2025,"journal":"Diabetes, obesity & metabolism, 27(6), 3453-3463","doi":"10.1111/dom.16372","pmid":"40181696","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"At 6-month follow-up, 69% of the overall cohort achieved HbA1c <7%, rising to 77% in the GLP-1 RA-naïve subgroup. Mean weight changes by subgroup were:\n\n- Overall cohort: -6.3 kg\n- Baseline HbA1c <7%: -7.1 kg\n- GLP-1 RA-naïve: -8.1 kg\n\nMore pronounced HbA1c reductions occurred in GLP-1 RA-naïve patients and those with higher baseline HbA1c (≥7%), while greater weight loss was seen in GLP-1 RA-naïve patients and those with lower baseline HbA1c (<7%). The cohort was 58% female, mean age 54, and 54% were already on a GLP-1 RA at baseline.","whyItMatters":"Clinical trials showed tirzepatide's impressive efficacy, but real-world data is essential to confirm these benefits hold up in everyday practice — where patients may have more comorbidities, take different medications, and adhere less perfectly. This study confirms that tirzepatide delivers meaningful blood sugar control and weight loss in routine clinical care.","specificNumbers":"","methodology":"Observational, single-cohort, pre-post study using the Healthcare Integrated Research Database (HIRD). Researchers identified commercially insured US adults (≥18 years) with type 2 diabetes who initiated tirzepatide between May 2022 and January 2023 and had HbA1c measurements at baseline and 6-month follow-up. Key outcomes (HbA1c and weight) were assessed overall and in subgroups by baseline GLP-1 RA use and HbA1c level.","limitations":"This is an observational study without a control group, so improvements cannot be definitively attributed to tirzepatide alone. The study used commercial insurance claims data, which may not represent uninsured or Medicare/Medicaid populations. Only 6 months of follow-up was assessed, and the cohort was predominantly non-Hispanic White. Adherence and persistence data were not detailed."},{"rthcId":"RPEP-12602","title":"Characteristics and Dosing Patterns of Tirzepatide Users with Type 2 Diabetes in the United States.","authors":"Mody, Reema; Desai, Karishma; Teng, Chia-Chen; Reznor, Gally; Stockbower, Grace; Grabner, Michael; Benneyworth, Brian D","year":2025,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 16(2), 307-327","doi":"10.1007/s13300-024-01684-6","pmid":"39794609","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12603","title":"Prediabetes and diabetes mellitus type II after ischemic stroke.","authors":"Moelgg, Kurt; Karisik, Anel; Scherer, Lukas; Buergi, Lucie; Dejakum, Benjamin; Komarek, Silvia; Granna, Julian; Boehme, Christian; Pechlaner, Raimund; Toell, Thomas; Knoflach, Michael; Kiechl, Stefan; Kaser, Susanne; Egger, Alexander; Griesmacher, Andrea; Mayer-Suess, Lukas","year":2025,"journal":"European stroke journal, 10(3), 822-828","doi":"10.1177/23969873241304301","pmid":"39763481","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"At baseline, 44.6% of 884 ischemic stroke patients had normoglycemia, 33.9% had prediabetes, and 21.5% had type 2 diabetes. After 1 year, normoglycemia decreased by 12.1 percentage points while prediabetes increased by 10.2 points and diabetes by 1.9 points. Statin therapy was the only significant risk factor for glycemic progression.\n\n23.4% (n=207) of the cohort would have met eligibility criteria for the SELECT trial on semaglutide in obese non-diabetics with prior cardiovascular disease. However, only one ongoing clinical trial is evaluating short-term cardiovascular risk reduction with these drugs in stroke patients specifically.","whyItMatters":"Stroke survivors face very high risk of recurrent cardiovascular events, and diabetes dramatically worsens that risk. GLP-1 receptor agonists like semaglutide have proven cardiovascular and metabolic benefits in other populations, yet they are barely being studied in stroke patients — a gap this study quantifies. Nearly a quarter of stroke patients could benefit from these peptide drugs but lack evidence to support their use.","specificNumbers":"","methodology":"Prospective observational cohort study using the STROKE-CARD Registry. 884 consecutive ischemic stroke patients were assessed for glycemic status (normoglycemia, prediabetes, type 2 diabetes) at baseline and at 1-year follow-up. Multivariate logistic regression identified factors associated with glycemic progression. Additionally, the authors reviewed ClinicalTrials.gov for ongoing GLP-1 RA and SGLT-2 inhibitor trials in acute ischemic stroke patients.","limitations":"This is an observational study from a single registry, which may limit generalizability. The association between statin use and glycemic progression could be confounded by other factors. The review of clinical trials is a snapshot in time and may not capture all ongoing or planned studies. The study did not assess whether GLP-1 RA use would actually prevent glycemic progression in stroke patients."},{"rthcId":"RPEP-12604","title":"The Role of the Dietitian in Weight Management of Adults With Obesity Without Diabetes Using Glucagon Like Peptide-1 Agonist Receptors: A Systematic Review and Meta-Analysis of Randomised Controlled Clinical Trials.","authors":"Moetaz, Israa; Abumweis, Suhad; Alqadi, Sarah; AbuGhoush, Mahmoud","year":2025,"journal":"Clinical obesity, 15(6), e70030","doi":"10.1111/cob.70030","pmid":"40530685","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12605","title":"A case report of semaglutide induced sarcopenia: causes of fatigue in older adults.","authors":"Mohamad, Azwan Aziz","year":2025,"journal":"Korean journal of family medicine, 46(4), 288-291","doi":"10.4082/kjfm.25.0008","pmid":"40223309","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12606","title":"Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists in Obese Patients Without Diabetes: A Systematic Review and Meta-Analysis.","authors":"Mohamed Ali Elbashir, Roaa; Elbashir, Azza; Urimuke Basake, Robert; Zakaria Ahmed Mohieldin, Amna; I A Elhaj, Najla; Ebrahim Mohamed Ebrahim, Fatima; Gase Ahmed, Waad; Abdelrahim Mohamed Mahgoub, Ola","year":2025,"journal":"Cureus, 17(11), e95938","doi":"10.7759/cureus.95938","pmid":"41341350","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Meta-analysis of 13 RCTs of GLP-1 RAs in obese/overweight patients without diabetes found:\n\n- Body weight reduction: -12.79% (95% CI: -15.12 to -10.46)\n- BMI reduction: -4.80 kg/m² (95% CI: -6.24 to -3.36)\n- Waist circumference: -9.78 cm (95% CI: -11.47 to -8.09)\n- Systolic BP: -6.32 mmHg (95% CI: -7.92 to -4.72)\n- Diastolic BP: -1.95 mmHg (95% CI: -3.21 to -0.69)\n\nWeight loss thresholds vs. placebo (risk ratios):\n- ≥5% weight loss: RR 2.98\n- ≥10% weight loss: RR 5.56\n- ≥15% weight loss: RR 9.50\n- ≥20% weight loss: RR 15.00\n\nTirzepatide showed greater reductions than semaglutide across outcomes.","whyItMatters":"This meta-analysis specifically addresses obese patients without diabetes — the fastest-growing market for GLP-1 drugs. The nearly 13% average weight loss, substantial waist circumference reduction, and blood pressure improvements demonstrate that these peptide drugs provide clinically meaningful benefits well beyond their original diabetes indication.","specificNumbers":"","methodology":"Systematic review and meta-analysis following PRISMA guidelines. Searched PubMed, Scopus, Web of Science, and Embase for RCTs of GLP-1 RAs in overweight/obese adults without diabetes. Two reviewers extracted data and assessed quality using Cochrane RoB 2. Thirteen trials were included.","limitations":"Only 13 trials were included, and trial durations and specific drugs varied. The comparison between tirzepatide and semaglutide was indirect (not head-to-head trials). Long-term weight maintenance after discontinuation was not assessed. Cost-effectiveness and long-term safety were not evaluated. The review did not separate results by specific GLP-1 RA."},{"rthcId":"RPEP-12607","title":"Intranasal Administration of KCNN2 Blocking Peptide Improves Deficits in Cognitive Flexibility in Mouse Model of Fetal Alcohol Spectrum Disorders.","authors":"Mohammad, Shahid; Wang, Li; Torii, Masaaki; Hashimoto-Torii, Kazue","year":2025,"journal":"The international journal of neuropsychopharmacology, 28(9)","doi":"10.1093/ijnp/pyaf055","pmid":"40795325","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12608","title":"Antimicrobial peptide LL37 is potent against non-growing Escherichia coli cells despite a slower action rate.","authors":"Mohammadi, Salimeh; Saucedo, Derek; Taheri-Araghi, Sattar","year":2025,"journal":"mSphere, 10(1), e0021124","doi":"10.1128/msphere.00211-24","pmid":"39714152","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12609","title":"Designing a Potent, Low-Toxicity Antimicrobial Peptide Inspired by Scorpion Peptides: Optimizing Expression and Activity.","authors":"Mohammadi, Zahra; Ayat, Hoda; Ahadi, Ali Mohammad","year":2025,"journal":"Probiotics and antimicrobial proteins","doi":"10.1007/s12602-025-10637-9","pmid":"40593394","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Mu-17 (LFRLIPSLIKRLISAFK, 17 residues) showed broad-spectrum antimicrobial activity with MICs of 1.5-5 μM against Gram-positive bacteria (Bacillus sp., Staphylococcus sp.), Gram-negative bacteria (E. coli), and Candida albicans. It inhibited breast cancer cell proliferation with an IC50 of 13 μM. Hemolytic activity was only 18% at 100 μM — significantly lower than many potent AMPs. The peptide forms an amphipathic alpha-helix and likely kills through membrane interaction. Recombinant production in E. coli was successfully optimized.","whyItMatters":"The antibiotic resistance crisis demands new antimicrobial approaches, but many potent antimicrobial peptides are too toxic to human cells for clinical use. Mu-17's combination of broad-spectrum killing, anticancer activity, and remarkably low hemolytic toxicity makes it stand out. The bio-inspired design approach — using evolutionary wisdom from scorpion venom as a starting point for rational engineering — demonstrates a scalable method for creating therapeutically useful peptides.","specificNumbers":"","methodology":"Researchers used bio-inspired design based on the conserved leucine zipper-like motif found across scorpion antimicrobial peptides. The gene encoding Mu-17 was synthesized, cloned into a bacterial expression system, and production conditions optimized to manage the peptide's inherent toxicity to the host bacteria. Purified recombinant Mu-17 was tested for antimicrobial activity (MIC determination against multiple organisms), anticancer activity (IC50 against breast cancer cells), hemolytic activity, and structural analysis.","limitations":"All testing was in vitro — no animal infection or cancer models were used. The MIC values against Gram-negative bacteria (E. coli only) need to be expanded to clinically relevant resistant strains like Pseudomonas, Acinetobacter, or Klebsiella. Stability in serum and biological fluids was not assessed. The recombinant production yield and cost were not quantified. The anticancer selectivity (cancer vs. normal cells) beyond hemolysis data needs further characterization."},{"rthcId":"RPEP-12610","title":"Tirzepatide Affect Sexual Function in Women: Case Report.","authors":"Mohammed, Ghada Farouk; Al-Dhubaibi, Mohammed Saleh; Bahaj, Saleh Salem; Mohammed, Rana Magdy","year":2025,"journal":"Clinical medicine insights. Case reports, 18, 11795476251347753","doi":"10.1177/11795476251347753","pmid":"40487373","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12611","title":"Mesalazine-Induced Myocarditis in a 17-Year-Old: A Case Report.","authors":"Mohammed, Mariam; Saripalli, Shirisha; Bendakji, Dana","year":2025,"journal":"Cureus, 17(11), e96792","doi":"10.7759/cureus.96792","pmid":"41393732","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12612","title":"Synthetic antimicrobial peptide LD4-PP protects the host against E. coli-induced cell death.","authors":"Mohanty, Soumitra; White, John Kerr; Yin, Yundi; Muhammad, Taj; Demirel, Isak; Strömstedt, Adam A; Gunasekera, Sunithi; Ferraz, Natalia; Göransson, Ulf; Brauner, Annelie","year":2025,"journal":"Frontiers in immunology, 16, 1705805","doi":"10.3389/fimmu.2025.1705805","pmid":"41415272","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12613","title":"Efficacy and Safety of Glucagon-Like Peptide-1 Receptor Agonists for Weight Loss Among Adults Without Diabetes : A Systematic Review of Randomized Controlled Trials.","authors":"Moiz, Areesha; Filion, Kristian B; Toutounchi, Helia; Tsoukas, Michael A; Yu, Oriana H Y; Peters, Tricia M; Eisenberg, Mark J","year":2025,"journal":"Annals of internal medicine, 178(2), 199-217","doi":"10.7326/ANNALS-24-01590","pmid":"39761578","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12614","title":"GLP-1 Receptor Agonists and Blood Pressure: A State-of-the-Art Review of Mechanisms, Evidence, and Clinical Implications.","authors":"Moiz, Areesha; Zolotarova, Tetiana; Filion, Kristian B; Eisenberg, Mark J","year":2025,"journal":"American journal of hypertension","doi":"10.1093/ajh/hpaf205","pmid":"41128495","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12615","title":"Mechanisms of GLP-1 Receptor Agonist-Induced Weight Loss: A Review of Central and Peripheral Pathways in Appetite and Energy Regulation.","authors":"Moiz, Areesha; Filion, Kristian B; Tsoukas, Michael A; Yu, Oriana Hy; Peters, Tricia M; Eisenberg, Mark J","year":2025,"journal":"The American journal of medicine, 138(6), 934-940","doi":"10.1016/j.amjmed.2025.01.021","pmid":"39892489","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12616","title":"The expanding role of GLP-1 receptor agonists: a narrative review of current evidence and future directions.","authors":"Moiz, Areesha; Filion, Kristian B; Tsoukas, Michael A; Yu, Oriana H Y; Peters, Tricia M; Eisenberg, Mark J","year":2025,"journal":"EClinicalMedicine, 86, 103363","doi":"10.1016/j.eclinm.2025.103363","pmid":"40727007","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12617","title":"Honeybee defense mechanisms: Role of honeybee gut microbiota and antimicrobial peptides in maintaining colony health and preventing diseases.","authors":"Mojgani, Naheed; Bagheri, Masoumeh; Ashique, Sumel; Islam, Anas; Moharrami, Mojtaba; Modirrousta, Hossein; Hussain, Abrar","year":2025,"journal":"Microbial pathogenesis, 198, 107161","doi":"10.1016/j.micpath.2024.107161","pmid":"39603566","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12618","title":"Hierarchical Reaction Logic Enables Computational Design of Complex Peptide Syntheses.","authors":"Molga, Karol; Beker, Wiktor; Roszak, Rafał; Czerwiński, Andrzej; Grzybowski, Bartosz A","year":2025,"journal":"Journal of the American Chemical Society, 147(9), 7644-7662","doi":"10.1021/jacs.4c17057","pmid":"39977835","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"By constraining computer-assisted synthesis planning with hierarchical reaction logic — dictating which subsets of reactions to apply at different planning stages — the algorithm successfully designed complete synthesis routes for complex peptide targets within minutes.\n\nThe approach was validated on clinically relevant targets including vancomycin (a complex glycopeptide antibiotic) and semaglutide (a large GLP-1 receptor agonist used for diabetes and obesity). Despite not being trained on any literature precedents, the computationally designed routes mimicked strategies used by human expert chemists.\n\nThe system incorporates protecting-group strategies and realistic pathway pricing, and supports both solid-phase and solution-phase synthesis modes, including C-to-N and N-to-C peptide extension strategies.","whyItMatters":"Peptide drug manufacturing is one of the biggest bottlenecks in bringing peptide therapeutics to market. Designing synthesis routes for complex peptides currently requires deep expertise and significant time. An algorithm that can produce expert-quality synthesis plans in minutes could accelerate drug development, reduce manufacturing costs, and make complex peptide drugs more accessible.","specificNumbers":"","methodology":"The researchers developed a hierarchical planning framework that layers reaction logic on top of existing retrosynthetic search algorithms. Rather than considering all possible reactions at every step, the system applies specific subsets of reaction transforms at different stages of route planning. The algorithm was tested on complex peptide targets without any training on published synthesis routes, and the resulting routes were compared to human expert strategies.","limitations":"The abstract does not report whether the computationally designed routes were actually executed in the laboratory to validate their practical feasibility. Computational route planning may not account for all real-world challenges such as side reactions, purification difficulties, and scalability issues. The comparison to human expert strategies is qualitative. The algorithm's performance on targets beyond vancomycin and semaglutide is not detailed in the abstract."},{"rthcId":"RPEP-12619","title":"Selective targeting of oncogenic KRAS G12D using peptide nucleic acid oligomers attached to cell-penetrating peptides.","authors":"Mondal, Jayati; Lam, Dennis; Gerritsen, Mary E; Brotz, Tilmann M; Kennedy, Jodi G; Rehlaender, Bruce; Ross, Arthur J; Levy, Daniel E; Bonagura, Christopher A; Lanzilotta, William N; McCormick, Frank; Rothman, Jeffrey H; Wolfe, Andrew L","year":2025,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2025.03.28.645837","pmid":"40236071","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12620","title":"Tirzepatide vs. semaglutide: clinical decision-making in the GLP-1 landscape.","authors":"Mondoh, Alvin; Crotty, Michael; le Roux, Carel W","year":2025,"journal":"Expert opinion on pharmacotherapy, 26(17), 1841-1854","doi":"10.1080/14656566.2025.2601060","pmid":"41351384","tags":[],"studyType":"Comparative Review","evidenceStrength":"strong","keyFinding":"Semaglutide and tirzepatide represent two complementary but distinct approaches to obesity pharmacotherapy. Tirzepatide (dual GIP/GLP-1 agonist) produces greater weight loss and broader metabolic benefits, while semaglutide (GLP-1 agonist) has demonstrated robust cardiovascular protection with dedicated outcomes data from the SELECT trial.\n\nThe review synthesizes data from the major clinical trial programs: STEP and SELECT for semaglutide, SURMOUNT and SUMMIT for tirzepatide. It frames the choice between the two drugs as a clinical decision that depends on the individual patient's priorities — maximum weight loss and metabolic improvement (favoring tirzepatide) versus proven cardiovascular risk reduction (favoring semaglutide). Both drugs require clinicians to treat obesity as a chronic disease needing ongoing pharmacological management rather than a lifestyle issue with a temporary fix.","whyItMatters":"This is the most common clinical question in obesity medicine today: which drug should I choose? By synthesizing the major trial data side by side, this review helps clinicians make evidence-based decisions. The key insight — that the two drugs have different strengths — means the choice isn't simply about which is 'better' but about matching the drug to the patient's specific clinical needs.","specificNumbers":"STEP trials (semaglutide) · SELECT trial (cardiovascular outcomes) · SURMOUNT trials (tirzepatide) · SUMMIT trial (heart failure) · Tirzepatide: greater weight loss · Semaglutide: proven CV protection · 2020-2025 literature","methodology":"Comparative review synthesizing data from pivotal clinical trials (STEP, SELECT, SURMOUNT, SUMMIT) for semaglutide and tirzepatide. Literature search conducted via PubMed and Google Scholar plus major cardiology and endocrinology publications from 2020 to 2025. Published in Expert Opinion on Pharmacotherapy.","limitations":"No head-to-head RCT directly comparing semaglutide and tirzepatide exists, so comparisons are indirect across different trial populations. The review reflects data available through early 2025; newer trial readouts may shift the balance. Narrative format rather than systematic review. Access, cost, and insurance coverage considerations are discussed but may vary significantly by region."},{"rthcId":"RPEP-12621","title":"3D bioprinting of biomimetic self-assembling peptides and neural stem cells for nervous tissue engineering.","authors":"Mondésert, Hugues; Malloggi, Chiara; Lazzaro, Andrea; Sala, Giulia; Corvaglia, Valentina; Forouharshad, Mahdi; Gelain, Fabrizio","year":2025,"journal":"Journal of materials chemistry. B, 13(44), 14386-14402","doi":"10.1039/d5tb00279f","pmid":"41090608","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Researchers successfully printed self-standing, ring-shaped peptide scaffolds up to 10 mm in diameter using a self-assembling peptide bioink and a microfluidic coaxial printhead.\n\nMurine neural stem cells encapsulated by either printing strategy showed slightly lower initial viability than controls, but viability increased over time. By day 7, the cells had adhered, sprouted, and differentiated into neurons, astrocytes, and oligodendrocytes, supporting the idea that these peptide hydrogels can function as bioinks for nervous tissue engineering.","whyItMatters":"Nervous tissue engineering needs materials that can be printed into stable 3D shapes without damaging fragile cells. This paper suggests self-assembling peptide hydrogels may offer a biomimetic scaffold that supports both printing and early neural-cell maturation, which is important for building more realistic repair models.","specificNumbers":"Up to 10 mm scaffold diameter · 2 cell-loading strategies · 7-day differentiation window","methodology":"The team formulated a self-assembling peptide bioink from linear, branched, and functionalized peptides designed to support cell adhesion and differentiation. They optimized print settings and rheology using a microfluidic RX1 bioprinter with a coaxial printhead, then printed ring-shaped self-standing scaffolds. Mouse neural stem cells were incorporated using two different loading strategies, and the resulting constructs were evaluated for structure, cell viability, attachment, sprouting, and differentiation over time.","limitations":"This was an early-stage tissue-engineering study, not a clinical trial. The work used murine neural stem cells rather than human cells, and the abstract does not provide detailed quantitative viability or differentiation results. It shows short-term promise over 7 days, but it does not establish long-term function, transplant performance, or therapeutic benefit in living nervous tissue."},{"rthcId":"RPEP-12622","title":"RGB Trichromatic Whiteness Assessment of Bio Analytical Chromatographic Tool Using Fluorescence for Quantitation of Semaglutide: Application to Pharmaceutical Preparations and Spiked Plasma.","authors":"Moneim, Mona M Abdel; Kamal, Miranda F; Hamdy, Mohamed M A","year":2025,"journal":"Journal of fluorescence, 35(8), 6467-6477","doi":"10.1007/s10895-024-03954-9","pmid":"39466481","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12623","title":"Design of antinociceptive peptide by grafting domains between scorpion β-neurotoxins.","authors":"Montero-Dominguez, Pavel Andrei; Restano-Cassulini, Rita; Magaña-Ávila, Lizeth Carolina; Almanza, Angélica; Mercado, Francisco; Corzo, Gerardo","year":2025,"journal":"Bioorganic chemistry, 162, 108592","doi":"10.1016/j.bioorg.2025.108592","pmid":"40398183","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12624","title":"Pharmacological treatment for patients with obesity and heart failure: Focus on glucagon-like peptide-1 receptor agonists. European Journal of Heart Failure expert consensus document.","authors":"Monzo, Luca; Savarese, Gianluigi; Mullens, Wilfried; Abdin, Amr; Bozkurt, Biykem; Chioncel, Ovidiu; El Hadidi, Seif; Gorter, Thomas M; Inciardi, Riccardo M; Petrie, Mark C; Schiattarella, Gabriele G; Stolfo, Davide; Metra, Marco; Girerd, Nicolas","year":2025,"journal":"European journal of heart failure, 27(11), 2465-2479","doi":"10.1002/ejhf.70082","pmid":"41309245","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12625","title":"Randomised trial comparing weight loss through lifestyle and GLP-1 receptor agonist therapy in people with MASLD.","authors":"Moolla, Ahmad; Poolman, Toryn; Othonos, Nantia; Dong, Jiawen; Smith, Kieran; Cornfield, Thomas; White, Sarah; Ray, David W; Mouchti, Sofia; Mózes, Ferenc E; Thomaides-Brears, Helena; Neubauer, Stefan; Cobbold, Jeremy F; Hodson, Leanne; Tomlinson, Jeremy W","year":2025,"journal":"JHEP reports : innovation in hepatology, 7(5), 101363","doi":"10.1016/j.jhepr.2025.101363","pmid":"40342635","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 29 MASLD patients without diabetes, after 12 weeks of matched weight loss:\n\nSimilar between groups:\n- Body composition changes, ALT reduction, liver steatosis reduction, and disease activity improvement\n- Subcutaneous adipose transcriptome, circulating proteome, and stool microbiome\n\nGLP-1RA advantages:\n- Improved glucose handling and fasting lipids\n- Significantly decreased de novo lipogenesis (DNL)\n\nAfter treatment withdrawal (12 weeks):\n- GLP-1RA (but not lifestyle) group showed elevated MMP-10, IL10RB, FGF-23, and Flt3L in circulation\n- Dysregulated adipose tissue gene expression\n- Changes suggestive of metabolic predisposition to weight regain","whyItMatters":"This study addresses two critical questions: Does GLP-1 therapy provide liver benefits beyond weight loss? And what happens metabolically when you stop? The answers — yes to extra benefits, and concerning rebound effects — have major implications for clinical practice. They support using GLP-1 drugs in MASLD while raising important questions about the consequences of treatment discontinuation.","specificNumbers":"","methodology":"Prospective, randomized experimental medicine study (EudraCT 2016-002045-36). 29 MASLD participants without T2D were randomized to lifestyle (~500 kcal deficit) or liraglutide for 12 weeks. Comprehensive phenotyping included de novo lipogenesis, liver MRI, body composition, adipose tissue RNA sequencing, circulating proteome, and stool microbiome. All investigations repeated after treatment and 12 weeks post-withdrawal.","limitations":"Small sample size (29 participants) limits statistical power. The 12-week treatment duration is relatively short. Only liraglutide was tested; other GLP-1 RAs may differ. The lifestyle group's adherence to calorie restriction after the study period wasn't tracked. Some withdrawal changes (proteome, microbiome) are exploratory and hypothesis-generating rather than confirmatory."},{"rthcId":"RPEP-12626","title":"Understanding the Opportunities in Dual Therapy and Emergency Department Utilization in Migraine Care.","authors":"Moore, Janine; Kurek, Alexis; Vo, Kimberly; Boone-Sautter, Kennedy; Jipping, Grace; Ahmed, Aiesha","year":2025,"journal":"Neurology. Clinical practice, 15(5), e200519","doi":"10.1212/CPJ.0000000000200519","pmid":"40852534","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12627","title":"Risk of Thyroid Tumors With GLP-1 Receptor Agonists: A Retrospective Cohort Study.","authors":"Morales, Daniel R; Bu, Fan; Viernes, Benjamin; DuVall, Scott L; Matheny, Michael E; Simon, Katherine R; Falconer, Thomas; Richter, Lauren R; Ostropolets, Anna; Lau, Wallis C Y; Man, Kenneth K C; Chattopadhyay, Shounak; Mathioudakis, Nestoras; Minty, Evan; Nishimura, Akihiko; Sun, Feng; Yin, Can; Seager, Sarah L; Chai, Yi; Zhou, Jin J; Lu, Yuan; Reyes, Carlen; Pistillo, Andrea; Duarte-Salles, Talita; Blacketer, Clair; Schuemie, Martijn J; Ryan, Patrick B; Krumholz, Harlan M; Hripcsak, George; Khera, Rohan; Suchard, Marc A","year":2025,"journal":"Diabetes care, 48(8), 1386-1394","doi":"10.2337/dc25-0154","pmid":"40465422","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12628","title":"How to individualize renoprotective therapy in obese patients with chronic kidney disease: a commentary by the Diabesity Working Group of the ERA.","authors":"Morales, Enrique; Martin, William P; Bevc, Sebastjan; Jenssen, Trond G; Miglinas, Marius; Trillini, Matias","year":2025,"journal":"Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 40(10), 1977-1988","doi":"10.1093/ndt/gfaf069","pmid":"40359159","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12629","title":"Obesity as a modifiable risk factor in patients with chronic kidney disease.","authors":"Morales, Enrique; Jenssen, Trond G; Bevc, Sebastjan; Miglinas, Marius; Martin, William P; Theodorakopoulou, Marieta; Buus Jørgensen, Morten; Trillini, Matias","year":2025,"journal":"Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association","doi":"10.1093/ndt/gfaf231","pmid":"41165722","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies a paradigm shift in CKD management: obesity-associated CKD phenotypes can now be therapeutically targeted using combinations of GLP-1 receptor agonists, SGLT2 inhibitors, and finerenone added to standard RAAS blockade. These multitargeted strategies address the pathophysiological interplay between obesity, metabolic syndrome, and kidney disease, with evidence of cardio-renal protection that could substantially alter disease progression.","whyItMatters":"CKD affects hundreds of millions of people worldwide, and obesity is both a major cause and accelerator of kidney disease. Until recently, treatment options were limited to RAAS blockade alone. The emergence of GLP-1 receptor agonists and other peptide-based therapies as cardio-renal protective agents represents a fundamental shift — obesity in CKD is now a treatable risk factor rather than an accepted comorbidity, potentially changing outcomes for millions of patients.","specificNumbers":"","methodology":"This is a narrative review synthesizing current evidence on the pathophysiology of obesity-related CKD, distinct clinical phenotypes associated with CKD progression, and the emerging therapeutic landscape including GLP-1 receptor agonists, SGLT2 inhibitors, and finerenone. No new experimental data were generated.","limitations":"As a narrative review, this paper reflects the authors' interpretation of existing evidence rather than a systematic analysis. The cardio-renal benefits of GLP-1 receptor agonists in CKD patients specifically with obesity are extrapolated partly from trials in broader populations. Long-term outcomes of these multitargeted combinations remain to be established in dedicated CKD+obesity trials."},{"rthcId":"RPEP-12630","title":"Assessment of B-Natriuretic Peptide Levels After Stage 1 Palliation in Hypoplastic Left Heart Syndrome Patients.","authors":"Morales-Demori, Raysa; Chen, Bingrui; Heinle, Jeffrey; Li, Meng; Anders, Marc","year":2025,"journal":"Pediatric cardiology, 46(7), 1833-1841","doi":"10.1007/s00246-024-03653-z","pmid":"39325157","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12631","title":"Various Bacillus and Paenibacillus Spp. Isolated From Soil Produce Compounds With Potent Antimicrobial Activity Against Clinically Relevant Pathogens.","authors":"Moran, Michael; Turner, Hogan; Yanchar, Joseph; Preece, Joshua; Ahlborn, Gene; Robison, Richard","year":2025,"journal":"MicrobiologyOpen, 14(6), e70179","doi":"10.1002/mbo3.70179","pmid":"41381995","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Of 29 soil isolates tested, Paenibacillus profundus strains 7.5 and M4.5 showed the most potent broad-spectrum antimicrobial activity, including significant inhibition of MRSA and carbapenem-resistant Enterobacterales (CRE).\n\nGenome mining of three producer strains using antiSMASH revealed biosynthetic gene clusters for:\n- Nonribosomal peptide synthetases (NRPSs)\n- Polyketide synthases (PKSs)\n- Ribosomally synthesized and post-translationally modified peptides (RiPPs)\n\nSeveral clusters matched known compounds (polymyxin B, paenilan, colistin, paenibacterin), while many had no known counterparts, suggesting potential for discovering novel antimicrobial peptides.","whyItMatters":"Antibiotic resistance is a global health emergency, and CRE infections in particular have very few treatment options. Soil bacteria are a proven source of antibiotics (most existing antibiotics were originally discovered from soil microbes). This study identifies new producer strains with potent activity against the most dangerous drug-resistant pathogens.","specificNumbers":"","methodology":"Twenty-nine Bacillus and Paenibacillus isolates from soil samples were tested against clinically relevant multidrug-resistant pathogens using both agar and broth-based antimicrobial assays. Species were identified via 16S rRNA sequencing. Genome mining of the most active strains was performed using antiSMASH to identify biosynthetic gene clusters for antimicrobial compound production.","limitations":"This is an early-stage discovery study — the specific antimicrobial compounds have not been purified or structurally characterized. The gene clusters suggest peptide production, but the actual molecules need to be isolated and tested. In vitro antimicrobial activity doesn't guarantee in vivo efficacy. Toxicity to human cells was not assessed."},{"rthcId":"RPEP-12632","title":"Problematic Pharmacokinetics: A Case of Recurrent Pancreatitis Post Discontinuation of a Glucagon-Like Peptide 1 Receptor Agonists.","authors":"Morehouse, Zachary P; Ledford, Jack D","year":2025,"journal":"Journal of pharmacy practice, 38(1), 187-192","doi":"10.1177/08971900241273188","pmid":"39109559","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12633","title":"Amylin and the amylin receptors in migraine: Is there another pathway to target?","authors":"Moreno-Ajona, David; Gosalia, Helin; Hoffmann, Jan; Goadsby, Peter J","year":2025,"journal":"Cephalalgia : an international journal of headache, 45(5), 3331024251340066","doi":"10.1177/03331024251340066","pmid":"40388703","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review presents several lines of evidence implicating amylin in migraine:\n\n- Amylin belongs to the same calcitonin/CGRP peptide family and shares receptor components with CGRP\n- In provocation studies, amylin can trigger migraine attacks, similar to CGRP\n- Some CGRP-targeting therapies also block amylin receptors, which may contribute to their efficacy\n- Amylin plasma levels have been identified as a potential migraine biomarker in at least one clinical study\n- Preclinical rodent studies suggest sex differences in amylin-mediated migraine mechanisms\n\nThe authors propose that understanding the distinct and overlapping mechanisms between amylin and CGRP signaling could advance migraine treatment options.","whyItMatters":"While CGRP-blocking drugs (like erenumab and fremanezumab) have transformed migraine care, about 40-50% of patients don't achieve adequate relief. If amylin represents an independent or overlapping migraine pathway, targeting it specifically could help non-responders. This is especially important because amylin and CGRP share receptor components, meaning some patients may benefit from dual blockade.","specificNumbers":"","methodology":"This was a narrative review of available evidence on amylin's role in migraine. The authors synthesized findings from provocation studies, biomarker research, preclinical animal studies, and pharmacological data on CGRP-targeting therapies that may also affect amylin receptors.","limitations":"The evidence base is still early-stage, with amylin's migraine role supported by limited clinical data (one biomarker study, provocation studies) and preclinical work. It's unclear whether targeting amylin independently of CGRP would be effective or safe. The review acknowledges that migraine is a complex disorder with many implicated molecules, and amylin may be one of several contributing pathways rather than a primary driver."},{"rthcId":"RPEP-12634","title":"In Vitro and In Vivo Characterization of Novel Cathelicidin-Based Peptides with Antimicrobial Activity Against Pseudomonas aeruginosa.","authors":"Moreno-Morales, Javier; Martín-Vilardell, Núria; Guardiola, Salvador; Vila-Farrés, Xavier; Cebrero, Tania; Babić, Marko; Ballesté-Delpierre, Clara; Kalafatović, Daniela; Giralt, Ernest; Pachón-Ibañez, María Eugenia; Vila, Jordi","year":2025,"journal":"Antibiotics (Basel, Switzerland), 14(8)","doi":"10.3390/antibiotics14080838","pmid":"40868032","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12635","title":"Effects of oral semaglutide on kidney outcomes in people with type 2 diabetes: a nationwide, multicentre, retrospective, observational study (Renal_ENDO2S-RWD substudy).","authors":"Moreno-Pérez, Oscar; Reyes-Garcia, Rebeca; Guillen-Morote, Cristina; Doulatram-Gamgaram, Viyey Kishore; Casado Cases, Carlos; Arias Mendoza, Nieves; Tejera-Pérez, Cristina; Cárdenas-Salas, Jersy; Martínez-Fuster, Sandra; Lardiés-Sánchez, Beatriz; Márquez-Pardo, Rosa; Pinés, Pedro; Tejera-Muñoz, Antonio; Fernández-García, José Carlos; Modrego-Pardo, Inés","year":2025,"journal":"Clinical kidney journal, 18(8), sfaf227","doi":"10.1093/ckj/sfaf227","pmid":"40800212","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12636","title":"Impact of oral semaglutide on serum urate levels in people with type 2 diabetes: A retrospective real-world analysis (URISEMA study).","authors":"Moreno-Pérez, Oscar; Tejera-Muñoz, Antonio; Carreño-Valdivia, Rubén; Rodríguez-Bedoya, María; Guillén-Morote, Cristina; Roldán-Sánchez, Ada; Andrés, Mariano","year":2025,"journal":"Seminars in arthritis and rheumatism, 74, 152807","doi":"10.1016/j.semarthrit.2025.152807","pmid":"40816061","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 236 patients (median age 64, BMI 33.8, baseline SU 5.2 mg/dL), oral semaglutide achieved the primary endpoint of SU < 6 mg/dL in a significant proportion at 12 months. Patients with baseline SU ≥ 6 mg/dL showed reductions of 0.6 and 0.8 mg/dL respectively (all p < 0.001). Changes were independent of metabolic control improvement, weight loss, or baseline use of GLP-1RAs or SGLT2 inhibitors. Switching from DPP-4 inhibitors was associated with particularly notable SU reductions.","whyItMatters":"Hyperuricemia and gout are common in type 2 diabetes and significantly affect quality of life. Finding that semaglutide lowers uric acid independently of its metabolic effects adds yet another potential benefit to this GLP-1 drug's growing therapeutic profile. For patients with diabetes and elevated uric acid — a combination that increases cardiovascular and kidney risk — semaglutide may address multiple problems simultaneously.","specificNumbers":"","methodology":"Retrospective real-world observational study (URISEMA) of 236 patients with type 2 diabetes prescribed oral semaglutide. Primary endpoint was achieving SU < 6 mg/dL at 12 months. Secondary endpoints included baseline factors associated with achieving target SU and average SU reductions. Multivariate analysis assessed independence from metabolic improvements.","limitations":"Retrospective observational design without a control group. The sample size (n=236) is modest. The abstract appears to have data presentation issues (incomplete sentences), suggesting some numerical findings may be unclear. Without randomization, residual confounding cannot be excluded despite multivariate analysis. Only oral semaglutide was studied — injectable formulations may differ. The mechanism of uric acid reduction was not investigated."},{"rthcId":"RPEP-12637","title":"Raman active diyne-girder conformationally constrained p53 stapled peptides bind to MDM2 for visualisation without fluorophores.","authors":"Morgan, Danielle C; McDougall, Laura; Knuhtsen, Astrid; Buetow, Lori; Steven, Craig F; Shepperson, Oscar A; Huang, Danny T; Hulme, Alison N; Jamieson, Andrew G","year":2025,"journal":"RSC chemical biology, 6(3), 394-403","doi":"10.1039/d4cb00288a","pmid":"39830683","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12638","title":"Temporal Microenvironment Mapping (μMap) of Intracellular Trafficking Pathways of Cell-Penetrating Peptides Across the Blood-Brain Barrier.","authors":"Morgan, Danielle C; Knutson, Steve D; Pan, Chenmengxiao Roderick; MacMillan, David W C","year":2025,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2025.01.15.633151","pmid":"39868165","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12639","title":"Engineering a single-chain immunoglobulin scaffold loaded with a latent-releasable cytotoxic pore-forming peptide.","authors":"Morillo, Izaskun; Zulaica, Joao; R Caballero, Asier; Auzmendi-Iriarte, Jaione; Largo, Eneko; Apellaniz, Beatriz; Carracedo, Arkaitz; Piva, Marco; Nieva, José L; Rujas, Edurne","year":2025,"journal":"Communications biology, 8(1), 1665","doi":"10.1038/s42003-025-09066-9","pmid":"41291002","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A single-chain IgG (scIgG) was engineered from atezolizumab (anti-PD-L1) with flexible linkers embedding the melittin sequence flanked by matriptase cleavage sites. Initial constructs with native melittin were too cytotoxic during production, leading to development of Pmod2-2, a melittin variant that retained potent pore-forming ability while being compatible with antibody fusion.\n\nThe resulting scIgG-Pmod2-2 hybrid preserved the Fab (antigen binding) and Fc (immune signaling) functionalities of atezolizumab, displayed favorable pharmacokinetics, and released the active cytotoxic peptide specifically in response to matriptase — an enzyme overexpressed in carcinomas.","whyItMatters":"This work addresses one of the biggest challenges in peptide therapeutics: how to deliver a potent but toxic peptide selectively to tumors while keeping it inactive elsewhere. By combining an antibody's targeting precision with a pore-forming peptide's killing power and enzyme-activated release, this approach could enable a new class of cancer therapeutics that are both more effective and safer than either component alone.","specificNumbers":"","methodology":"Researchers used protein engineering to create single-chain IgG constructs based on atezolizumab with melittin sequences embedded in flexible linkers. Matriptase-cleavable flanking regions were added for tumor-specific activation. After initial constructs failed due to cytotoxicity during expression in producer cells, they designed Pmod2-2, a modified melittin variant. The hybrid was characterized for antibody functionality (Fab and Fc activity), pharmacokinetics, and protease-responsive peptide release.","limitations":"This is an engineering and proof-of-concept study — anti-tumor efficacy in animal models is not reported in the abstract. The matriptase cleavage specificity in complex in vivo environments needs validation, as other proteases could potentially cause off-target release. The pharmacokinetics of the full hybrid may differ from standard antibodies due to the embedded peptide. Manufacturing scalability of this complex construct was not addressed."},{"rthcId":"RPEP-12640","title":"Fragment-Based Discovery of an Oral Calcitonin Gene-Related Peptide Receptor Antagonist for the Treatment of Migraine.","authors":"Morita, Naohide; Furuya, Noritaka; Momose, Takaki; Kondo, Atsushi; Ishikawa, Takehiro; Wanajo, Isao; Nishikawa, Michiyo; Ozawa, Motoyasu; Kajino, Masaoki; Harada, Hiroshi; Matsuzawa, Akane; Tsuchioka, Akihiro; Hikawa, Hidemasa; Azumaya, Isao","year":2025,"journal":"Journal of medicinal chemistry, 68(14), 14919-14944","doi":"10.1021/acs.jmedchem.5c01127","pmid":"40608025","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12641","title":"Immunohistochemical Analysis of Maxillary Nerve Distribution in Rats.","authors":"Moriyama, Hikaru; Nakase, Yuki; Ambe, Kimiharu; Kawaai, Hiroyosi; Yamazaki, Shinya","year":2025,"journal":"Anesthesia progress, 72(3), 151-158","doi":"10.2344/23-0035","pmid":"40925620","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12642","title":"Targeting Obesity for Heart Failure.","authors":"Morris, Emily; Rider, Oliver","year":2025,"journal":"European cardiology, 20, e38","doi":"10.15420/ecr.2025.37","pmid":"41523265","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12643","title":"Intestinal adaptation to cold-induced metabolic demand and feeding requires GLP-1R and GLP-2R signalling.","authors":"Morrow, Nadya M; Hanson, Antonio A; Fong-McMaster, Claire; Livingston, Dawson B H; Osman, Hoda; Hamilton, Lauren; Trzaskalski, Natasha A; Locatelli, Cassandra A A; Bellefleur, Mélodie N; Messika-Zeitoun, Ethel; Cino, Sebastian M; Pulente, Serena M; Abramchuk, Iryna; Zhao, Xiaoling; Lorenzen-Schmidt, Ilka; Morissette, Arianne; Power, Krista A; Harper, Mary-Ellen; Mulvihill, Erin E","year":2025,"journal":"Communications biology, 9(1), 25","doi":"10.1038/s42003-025-09281-4","pmid":"41345787","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Over five weeks at 6°C, all mice ate significantly more food. Wild-type and GLP-1R/GIPR double knockout mice showed increased jejunal circumference, villi length, and crypt depth — but mice lacking both GLP-1R and GLP-2R did not show these gut adaptations. This pinpoints the GLP-2 receptor as essential for cold-induced intestinal expansion. Despite elevated plasma active GLP-1 levels, villi lengthening did not occur without GLP-2R. However, GLP-1R signaling was sufficient for body weight gain even when gut structural adaptation failed.","whyItMatters":"Understanding how GLP-1 and GLP-2 peptides control intestinal adaptation has direct implications for patients on GLP-1-based drugs (semaglutide, liraglutide) and GLP-2 therapies (teduglutide for short bowel syndrome). This study shows these peptide systems have non-overlapping functions — blocking one doesn't compensate for the other — which is important for predicting side effects and designing combination therapies.","specificNumbers":"","methodology":"Male and female wild-type, double incretin receptor knockout (DIRKO: Glp1r-/-Gipr-/-), and GLP double receptor knockout (GLPDRKO: Glp1r-/-Glp2r-/-) mice were housed at either 6°C (cold) or 27°C (thermoneutral) for five weeks. Researchers measured food intake, body weight, jejunal circumference, villi length, crypt depth, and plasma GLP-1 levels.","limitations":"This is a mouse study using extreme cold stress (6°C for 5 weeks), which does not directly model any common human condition. The genetic knockout approach eliminates receptors from birth, so compensatory developmental changes may occur that wouldn't apply to pharmacological receptor blockade in adults. The study did not examine long-term outcomes beyond five weeks or assess nutrient absorption directly."},{"rthcId":"RPEP-12644","title":"Topically applied GHK as an anti-wrinkle peptide: Advantages, problems and prospective.","authors":"Mortazavi, Seyedeh Maryam; Mohammadi Vadoud, Seyyed Ali; Moghimi, Hamid Reza","year":2025,"journal":"BioImpacts : BI, 15, 30071","doi":"10.34172/bi.30071","pmid":"39963574","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12645","title":"Pregnancy outcomes following first trimester exposure to semaglutide.","authors":"Morton, Adam; He, Jinwen","year":2025,"journal":"Obstetric medicine, 1753495X251346330","doi":"10.1177/1753495X251346330","pmid":"40487375","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12646","title":"Designing an optimized theta-defensin peptide for HIV therapy using in-silico approaches.","authors":"Mosalanejad, Zahra; Faraji, Seyed Nooreddin; Rahbar, Mohammad Reza; Gholami, Ahmad","year":2025,"journal":"Journal of integrative bioinformatics, 22(1)","doi":"10.1515/jib-2023-0053","pmid":"40098445","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12647","title":"Agonists for glutamate, acetylcholine, and orexin cause non-photic phase shifts when applied to the intergeniculate leaflet.","authors":"Moshirpour, Mahtab; Horsley, Katelyn G; Puche Saud, Susana; McCance, Chantelle; Scotland, Maeve; Antle, Michael C","year":2025,"journal":"Neuroscience, 574, 114-123","doi":"10.1016/j.neuroscience.2025.04.007","pmid":"40194656","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"When the glutamate agonist NMDA and the acetylcholine agonist carbachol were each applied separately to the IGL, both caused non-photic phase shifts in circadian rhythms. Orexin alone produced only small, inconsistent shifts. However, combining carbachol and NMDA together actually inhibited each other's effects. Adding orexin to this two-drug cocktail reversed the inhibition and produced the largest phase shifts observed in the study.\n\nBlocking acetylcholine muscarinic receptors or orexin receptors individually during sleep deprivation did not prevent phase shifting, indicating that no single arousal pathway is solely responsible — the IGL relies on redundant, convergent inputs.","whyItMatters":"Understanding how non-light signals reset the body clock could eventually lead to therapies for circadian disruption conditions like jet lag, shift work disorder, and irregular sleep-wake patterns. The finding that orexin enhances clock resetting when combined with other signals highlights how neuropeptides don't always act in isolation — they often work as modulators within complex signaling networks.","specificNumbers":"","methodology":"Researchers used mice housed in constant darkness to isolate circadian rhythm behavior. They surgically implanted cannulas targeting the intergeniculate leaflet and injected various neurotransmitter agonists (carbachol for acetylcholine, NMDA for glutamate, orexin) at circadian time 6 (midday equivalent). They also tested receptor blockers (atropine for muscarinic receptors, MK-6096 for orexin receptors) during a 3-hour sleep deprivation protocol. Phase shifts in wheel-running activity were measured to assess circadian clock changes.","limitations":"The study was conducted exclusively in mice under constant darkness conditions, which may not directly translate to human circadian biology. Drug injections were targeted to a very small brain region, making it difficult to rule out spread to nearby areas. The sleep deprivation protocol used (novel object interaction) is a specific arousal paradigm that may not capture all forms of non-photic input. Sample sizes for individual experimental groups were not explicitly reported in the abstract."},{"rthcId":"RPEP-12648","title":"The state of insurance coverage of calcitonin gene-related peptide-targeted medications and its impact on the implementation of the American Headache Society's 2024 consensus statement: An interrupted time-series analysis.","authors":"Moskatel, Leon S; Slusky, David J G","year":2025,"journal":"Headache","doi":"10.1111/head.15027","pmid":"40719064","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12649","title":"Antidepressants and Weight Gain: An Update on the Evidence and Clinical Implications.","authors":"Moss, Lauren; Laudenslager, Marci; Steffen, Kristine J; Sockalingam, Sanjeev; Coughlin, Janelle W","year":2025,"journal":"Current obesity reports, 14(1), 2","doi":"10.1007/s13679-024-00598-5","pmid":"39753939","tags":[],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Antidepressant-related weight gain is a common and clinically significant problem that can worsen metabolic health in patients already at elevated risk due to depression. The review identifies several strategies to manage this:\n\n1. **Weight-neutral alternatives**: Bupropion, fluoxetine, and the newer agent gepirone can treat depression without the weight gain associated with many other antidepressants.\n2. **Genetic prediction**: Metabolizer phenotypes and inflammation markers may help predict which patients are most susceptible to weight gain on specific antidepressants.\n3. **GLP-1 receptor agonists**: Liraglutide and metformin are discussed as pharmacotherapy options to counteract antidepressant-induced weight gain.\n4. **Integrated behavioral interventions**: Combining lifestyle modifications with medication management can help offset metabolic risks.","whyItMatters":"Depression and obesity frequently co-occur and worsen each other. The antidepressants used to treat depression often cause significant weight gain, creating a cruel clinical paradox. GLP-1 agonists like liraglutide are increasingly being considered as part of the solution — treating the weight gain that antidepressants cause while potentially also helping with depression symptoms. This intersection of psychiatric and metabolic treatment is becoming a major clinical frontier.","specificNumbers":"Weight-neutral options: bupropion, fluoxetine, gepirone · Pharmacotherapy for weight gain: GLP-1 agonists (liraglutide), metformin · Genetic factors: metabolizer phenotypes, inflammation · Depression increases metabolic risk independently","methodology":"This is a narrative review examining recent research on the relationship between antidepressant use and weight change. The authors surveyed evidence on genetic predictors of susceptibility, weight-neutral antidepressant alternatives, and pharmacological and behavioral interventions for managing antidepressant-related weight gain.","limitations":"As a narrative review, it doesn't systematically quantify the weight gain associated with each antidepressant or the efficacy of GLP-1 agonists specifically for antidepressant-induced weight gain. The use of GLP-1 agonists in this context is relatively new and evidence is still accumulating. Individual responses to antidepressants and weight management strategies vary widely."},{"rthcId":"RPEP-12650","title":"Targeted Delivery of Anti-TGF-β1-siRNA Using PDGFR-β Peptide-Modified Chitosan Nanoparticles for the Treatment of Liver Fibrosis.","authors":"Mostafa, Salma; Shetab Boushehri, Maryam A; Ezzat, Aya A; Weiskirchen, Ralf; Lamprecht, Alf; Mansour, Samar; Tammam, Salma N","year":2025,"journal":"Molecular pharmaceutics, 22(11), 6741-6758","doi":"10.1021/acs.molpharmaceut.5c00715","pmid":"41014631","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Chitosan nanoparticles decorated with a high density of PDGF-β binding peptide and loaded with anti-TGF-β1 siRNA significantly reduced hepatic TGF-β1 levels by approximately 65% and fibronectin levels by approximately 63% in a CCl4-induced liver fibrosis mouse model. Pretreatment with collagenase-loaded nanoparticles (to break down the dense scar tissue barrier) further reduced both markers by an additional ~10%. Histopathological evaluation confirmed reduced portal inflammation, absence of fibroblastic proliferation between hepatocytes, and decreased collagen deposition. The nanoparticles had 92.39% siRNA encapsulation efficiency, a diameter of 103 nm, and showed no organ-specific toxicity at doses up to 120 mg/kg over 4 weeks.","whyItMatters":"Liver fibrosis progresses to cirrhosis and liver failure, and there are currently no approved anti-fibrotic drugs for the liver. The dense scar tissue itself creates a delivery barrier that prevents drugs from reaching the cells driving fibrosis. This study demonstrates a clever two-pronged approach — using peptide targeting to find the right cells and collagenase pretreatment to penetrate the scar tissue barrier — that could open a new therapeutic pathway.","specificNumbers":"","methodology":"Researchers engineered chitosan nanoparticles (~103 nm diameter) modified with varying densities of PDGF-β receptor binding peptides as a targeting mechanism. The nanoparticles were loaded with anti-TGF-β1 siRNA (92.4% encapsulation efficiency). Safety was tested in healthy mice with biweekly dosing up to 120 mg/kg for 4 weeks. Biodistribution was assessed in both healthy and fibrotic mice. Efficacy was evaluated in a CCl4-induced liver fibrosis mouse model, with and without pretreatment using collagenase-loaded nanoparticles. Outcomes were measured by TGF-β1 and fibronectin levels plus Masson Trichrome histological staining.","limitations":"This is a preclinical mouse study using a chemical (CCl4) fibrosis model, which may not perfectly replicate human liver fibrosis. The treatment duration was relatively short (4 weeks), and long-term efficacy and safety are unknown. Translation from mouse to human involves significant challenges in dosing, biodistribution, and immune response to nanoparticles. No comparison to existing fibrosis treatments was made."},{"rthcId":"RPEP-12651","title":"Targeting peptide-MHC complexes with designed T cell receptors and antibodies.","authors":"Motmaen, Amir; Jude, Kevin M; Wang, Nan; Minervina, Anastasia; Feldman, David; Lichtenstein, Mauriz A; Ebenezer, Abishai; Correnti, Colin; Thomas, Paul G; Garcia, K Christopher; Baker, David; Bradley, Philip","year":2025,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2025.11.19.689381","pmid":"41332722","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12652","title":"Low-intensity muscle contraction exercise reduces pain sensitivity by modulating peripheral pathology and spinal sensitization in end-stage knee osteoarthritis rats.","authors":"Motokawa, Satoko; Sakamoto, Junya; Sasaki, Ryo; Nishi, Yuki; Honda, Yuichiro; Takahashi, Ayumi; Okita, Minoru","year":2025,"journal":"Frontiers in pain research (Lausanne, Switzerland), 6, 1644177","doi":"10.3389/fpain.2025.1644177","pmid":"41090182","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12653","title":"Systemic semaglutide provides a mild vasoprotective and antineuroinflammatory effect in a rat model of ocular hypertensive glaucoma.","authors":"Mouhammad, Zaynab A; Rombaut, Anne; Bermúdez, Mariana Yolotzin García; Vohra, Rupali; Tribble, James R; Williams, Pete A; Kolko, Miriam","year":2025,"journal":"Molecular brain, 18(1), 54","doi":"10.1186/s13041-025-01224-8","pmid":"40597179","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12654","title":"Persistence, switching, and healthcare use after initiating calcitonin gene-related peptide inhibitors: a real-world assessment.","authors":"Moura, Cristiano S; Randall, Jason R; Klarenbach, Scott; Behlouli, Hassan; Luu, Huong; Amoozegar, Farnaz; Kaboré, Jean-Luc; Bernatsky, Sasha","year":2025,"journal":"The journal of headache and pain, 27(1), 19","doi":"10.1186/s10194-025-02167-0","pmid":"41388239","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12655","title":"Off-The-Shelf Multivalent Nanoconjugate Cancer Vaccine Rescues Host Immune Response against Melanoma.","authors":"Moura, Liane If; Malfanti, Alessio; Matos, Ana I; Peres, Carina; Armiñán, Ana; Duro-Castaño, Aroa; Conejos-Sánchez, Inmaculada; Medel, María; Đorđević, Snežana; Carrascosa, Paula; Carreira, Bárbara; Acúrcio, Rita C; Xavier-Ferreira, Helena; Hernández-Barranco, Alberto; Castellano, Elena; Roselló, Esther; Machado, José C; Peinado, Héctor; Vicent, María J; Florindo, Helena F","year":2025,"journal":"Advanced materials (Deerfield Beach, Fla.), 37(16), e2417348","doi":"10.1002/adma.202417348","pmid":"39937158","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12656","title":"Components of Mineralocorticoid Receptor System in Human DRG Neurons Co-Expressing Pain-Signaling Molecules: Implications for Nociception.","authors":"Mousa, Shaaban A; Hong, Xueqi; Metwally, Elsayed Y; Tafelski, Sascha; Wandrey, Jan David; Piontek, Jörg; Treskatsch, Sascha; Schäfer, Michael; Shaqura, Mohammed","year":2025,"journal":"Cells, 14(15)","doi":"10.3390/cells14151142","pmid":"40801575","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12657","title":"The role of glucagon-like peptide-1 receptor agonists in weight regain treatment or prevention after bariatric surgery: a systematic review and meta-analysis.","authors":"Mousavi, Asma; Shojaei, Shayan; Azarboo, Alireza; Bahri, Razman Arabzadeh; Mohammadi, Sara; Alilou, Sanam; Yousefifar, Shaygan; Maleki, Saba; Radkhah, Hanieh","year":2025,"journal":"Eating and weight disorders : EWD, 30(1), 70","doi":"10.1007/s40519-025-01770-z","pmid":"40877612","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12658","title":"A Chimeric Peptide-Carbon Quantum Dot Nanobiohybrid System for Gene Delivery to Macrophage Cells.","authors":"Mousazadeh, Marziyeh; Nikkhah, Maryam; Moradi, Sajad; Seyed, Negar; Rafati, Sima; Hosseinkhani, Saman","year":2025,"journal":"Applied biochemistry and biotechnology, 197(12), 7882-7898","doi":"10.1007/s12010-025-05415-w","pmid":"41108345","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12659","title":"The Role of NT-proBNP Levels in the Diagnosis of Hypertensive Heart Disease.","authors":"Mouzarou, Angeliki; Hadjigeorgiou, Nikoleta; Melanarkiti, Despo; Plakomyti, Theodora Eleni","year":2025,"journal":"Diagnostics (Basel, Switzerland), 15(1)","doi":"10.3390/diagnostics15010113","pmid":"39795641","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12660","title":"Nutritional priorities to support GLP-1 therapy for obesity: A joint advisory from the American College of Lifestyle Medicine, the American Society for Nutrition, the Obesity Medicine Association, and the Obesity Society.","authors":"Mozaffarian, Dariush; Agarwal, Monica; Aggarwal, Monica; Alexander, Lydia; Apovian, Caroline M; Bindlish, Shagun; Bonnet, Jonathan; Butsch, W Scott; Christensen, Sandra; Gianos, Eugenia; Gulati, Mahima; Gupta, Alka; Horn, Debbie; Kane, Ryan M; Saluja, Jasdeep; Sannidhi, Deepa; Stanford, Fatima Cody; Callahan, Emily A","year":2025,"journal":"Obesity pillars, 15, 100181","doi":"10.1016/j.obpill.2025.100181","pmid":"40673264","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12661","title":"Nutritional priorities to support GLP-1 therapy for obesity: A joint Advisory from the American College of Lifestyle Medicine, the American Society for Nutrition, the Obesity Medicine Association, and The Obesity Society.","authors":"Mozaffarian, Dariush; Agarwal, Monica; Aggarwal, Monica; Alexander, Lydia; Apovian, Caroline M; Bindlish, Shagun; Bonnet, Jonathan; Butsch, W Scott; Christensen, Sandra; Gianos, Eugenia; Gulati, Mahima; Gupta, Alka; Horn, Debbie; Kane, Ryan M; Saluja, Jasdeep; Sannidhi, Deepa; Stanford, Fatima Cody; Callahan, Emily A","year":2025,"journal":"Obesity (Silver Spring, Md.), 33(8), 1475-1503","doi":"10.1002/oby.24336","pmid":"40445127","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12662","title":"A Narrative Review of the Interplay Between Carbohydrate Intake and Diabetes Medications: Unexplored Connections and Clinical Implications.","authors":"Mphasha, Mabitsela Hezekiel; Vagiri, Rajesh","year":2025,"journal":"International journal of molecular sciences, 26(2)","doi":"10.3390/ijms26020624","pmid":"39859337","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12663","title":"Bioactivity assessment of peptides derived from salted jellyfish (Rhopilema hispidum) byproducts.","authors":"Muangrod, Pratchaya; Charoenchokpanich, Wiriya; Roytrakul, Sittiruk; Rungsardthong, Vilai; Charoenlappanit, Sawanya; Wonganu, Benjamaporn; Tabtimmai, Lueacha; Chamsodsai, Phumin; Casanova, Federico; Thumthanaruk, Benjawan","year":2025,"journal":"PloS one, 20(2), e0318781","doi":"10.1371/journal.pone.0318781","pmid":"39932945","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12664","title":"T-cell receptor/CD28-targeted immunotherapeutics selectively drive naive T-cell expansion to generate functional HIV-specific responses.","authors":"Mueller, April L; Lamcaj, Sara; Garforth, Scott; Hiner, Christopher; Woodley, Darien; Paraiso, Kitt; Mi, Tian; Low, Simon; Youngblood, Ben; Almo, Steven C; Goldstein, Harris","year":2025,"journal":"Journal of virology, 99(9), e0018825","doi":"10.1128/jvi.00188-25","pmid":"40762498","tags":[],"studyType":"in-vitro","evidenceStrength":"low","keyFinding":"Researchers developed Immuno-STAT (IST), a protein scaffold that delivers peptide-specific T cell receptor activation plus CD28 costimulatory signals to expand HIV-specific killer T cells from the naive immune repertoire. The IST platform succeeded where conventional dendritic cell methods failed: it expanded naive SL9-specific CD8+ T cells (targeting a key HIV epitope) that dendritic cells could not stimulate.\n\nThe IST-generated T cells showed potent cytotoxicity against HIV-infected targets, diverse T cell receptor clonotypes (suggesting broad coverage), memory-differentiated phenotypes, and polyfunctionality — all critical qualities for an effective HIV-targeting immune response.","whyItMatters":"A functional HIV cure remains one of medicine's biggest challenges. Current adoptive cell therapy approaches are limited by the difficulty of expanding HIV-specific T cells outside the body. This new peptide-based platform (IST) overcomes that barrier by activating naive T cells that conventional methods can't reach, potentially enabling the generation of targeted immune responses against conserved HIV epitopes and immune escape variants.","specificNumbers":"Targets 2 epitopes: HIV SL9 + melanoma MART-1 · Polyfunctional CD8+ T cells generated · Diverse TCR clonotypes · IST succeeded where DC-based expansion failed for SL9","methodology":"Proof-of-concept study developing the Immuno-STAT protein scaffold platform. Researchers designed dimeric proteins that present peptide epitopes (HIV SL9 or melanoma MART-1) with optional CD28 costimulation to naive CD8+ T cells ex vivo. They compared IST-expanded T cells against those generated by conventional peptide-loaded dendritic cells, assessing expansion efficiency, cytotoxicity, TCR diversity, polyfunctionality, and memory phenotype.","limitations":"This is an in vitro proof-of-concept study — no human patients were treated with IST-generated T cells. The approach has not been tested in vivo for efficacy against HIV infection. The scalability and safety profile of adoptive transfer of these cells remains unknown. Manufacturing complexity and cost of the IST platform are not addressed."},{"rthcId":"RPEP-12665","title":"Transient Expression of Nicotiana tabacum Silicon-Induced Histidine-Rich Defensins in N. benthamiana Limits Necrotic Lesion Development Caused by Phytopathogenic Fungi.","authors":"Muhindi, Stephen; Zellner, Wendy; Marzano, Shin-Yi; Boldt, Jennifer; Leisner, Scott","year":2025,"journal":"Phytopathology, 115(1), 35-43","doi":"10.1094/PHYTO-05-24-0162-R","pmid":"39348470","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12666","title":"Liraglutide enhances myotube differentiation and muscle contractile activity upon electric pulse stimulation in mouse skeletal muscle cells.","authors":"Mukai, Risa; Kojima, Ayumu; Morisasa, Mizuki; Tawara, Wakako; Mori, Tsukasa; Goto-Inoue, Naoko","year":2025,"journal":"Bioscience, biotechnology, and biochemistry, 89(8), 1114-1119","doi":"10.1093/bbb/zbaf060","pmid":"40258338","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12667","title":"Short-peptide based supramolecular nanocomposite hydrogels for the disruption of polymicrobial biofilms and accelerated infected wound healing.","authors":"Mukherjee, Sudip; Núñez-Martínez, Manuel; Illescas-Lopez, Sara; Jeyakumar, Archanna; Lopez-Lopez, Modesto Torcuato; Cuerva, Juan Manuel; Bhatia, Vaibhav; Gavira, José Antonio; Álvarez de Cienfuegos, Luis; Haldar, Jayanta","year":2025,"journal":"Biomaterials science, 13(24), 6818-6836","doi":"10.1039/d5bm00761e","pmid":"41140241","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12668","title":"Novel antimicrobial peptides and peptide-microbiome crosstalk in Appalachian salamander skin.","authors":"Muletz-Wolz, Carly R; Urrutia-Carter, Julian; Osborne, Owen; Kutos, Steve; Meneses Montano, Jose; Madison, Joseph D; Gratwicke, Brian; Racharaks, Ratanachat; Roncal, Norma E; Jimenez, Randall R; Ellison, Amy; Cleland, Timothy P","year":2025,"journal":"NPJ biofilms and microbiomes, 11(1), 213","doi":"10.1038/s41522-025-00837-0","pmid":"41266339","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12669","title":"Changes in use of acute and preventive medications for migraine after erenumab initiation over 12 months: A United States retrospective cohort study.","authors":"Multani, Jasjit K; Urman, Robert; Park, Andrew S; Gill, Karminder; Vuvu, Fiston; Sun, Kainan; Patel, Leah B; Stockl, Karen M; Hawkins, Kevin; Rhyne, Christopher; Bensink, Mark E","year":2025,"journal":"Headache, 65(1), 68-79","doi":"10.1111/head.14820","pmid":"39248147","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12670","title":"Growth Differentiation Factor-15 is Associated With Acute Myocardial Infarction and Death at 30 and 90 Days in Emergency Department Patients With Suspected Acute Coronary Syndrome.","authors":"Mumma, Bryn E; Bhandari, Nipun; Tran, Nam K; Ford, James S; Christenson, Robert; Wilkerson, R Gentry; Madsen, Troy; Weaver, Michael T; Yi, Fan; Zhang, Xiaoxi; Allen, Brandon R; Mahler, Simon A","year":2025,"journal":"Journal of the American Heart Association, 14(19), e038675","doi":"10.1161/JAHA.124.038675","pmid":"41025470","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12671","title":"Tirzepatide Versus Semaglutide for Weight Loss in Overweight and Obese Adults: A Systematic Review and Meta-Analysis of Direct Comparative Studies.","authors":"Munawar, Nazish; Mahato, Aakash; Rawat, Anurag; Gill, Fahad Shaukat; Kumar, Daksh; Katwal, Susant; Wei, Calvin R; Ali, Neelum","year":2025,"journal":"Cureus, 17(6), e86080","doi":"10.7759/cureus.86080","pmid":"40666599","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tirzepatide demonstrated significantly superior weight loss compared to semaglutide across 7 studies (28,980 participants). The pooled standardized mean difference was 0.75 (95% CI: 0.52–0.92) favoring tirzepatide.\n\nAt 6 months, tirzepatide achieved a mean difference of 1.33 percentage points greater weight reduction (95% CI: 0.58–2.08). Participants on tirzepatide had significantly higher odds of achieving ≥10% weight loss compared to semaglutide (OR: 0.21, 95% CI: 0.06–0.78). However, heterogeneity was very high across studies (I² >90%).","whyItMatters":"With tirzepatide and semaglutide both becoming blockbuster weight-loss drugs, patients and doctors need to know which works better. This is one of the first meta-analyses to pool head-to-head comparison data, providing stronger evidence than individual studies alone. The finding that tirzepatide's dual-receptor approach outperforms GLP-1-only targeting has implications for drug selection and future drug development.","specificNumbers":"","methodology":"Systematic review and meta-analysis of studies directly comparing tirzepatide and semaglutide for weight management. Four databases (PubMed, EMBASE, Web of Science, Cochrane Library) were searched through April 2025. Seven studies met inclusion criteria: 5 observational studies and 2 randomized controlled trials, with follow-up ranging from 6 to 12 months. Data were pooled using random-effects models in Review Manager 5.4.1.","limitations":"High heterogeneity (I² >90%) indicates substantial variation across studies, weakening the pooled estimates. Only 2 of 7 studies were randomized controlled trials; the remaining 5 were observational, introducing potential confounding. Follow-up was limited to 6–12 months. Different doses and formulations of both drugs were used across studies. Safety and tolerability were not comprehensively compared."},{"rthcId":"RPEP-12672","title":"Extensive Arteriovenous Fistula Thrombosis With Glucagon-Like Peptide-1 Agonist.","authors":"Muneeb, Muhammad; Choi, Elizabeth; Rodriguez, Coralys; Goyal, Kanika; Bhura, Zainab; Hannoudi, Ghadeer","year":2025,"journal":"Cureus, 17(7), e88015","doi":"10.7759/cureus.88015","pmid":"40821211","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A 55-year-old African American female with a history of deceased donor renal transplantation developed:\n\n• Extensive thrombosis of the left AV fistula\n• Thrombosis extending to the brachiocephalic vein\n• Thrombosis of both radial and ulnar arteries\n• Symptoms: pain, swelling, erythema, fever, chills, and loss of palpable thrill over the fistula for approximately one week\n\nComprehensive prothrombotic workup (both inherited and acquired hypercoagulable states) was completely unremarkable. The only identifiable change was a recent dose escalation of her GLP-1 receptor agonist. After the drug was discontinued, no further thrombotic events occurred during follow-up, supporting a temporal and causal association.","whyItMatters":"With tens of millions of patients now taking GLP-1 drugs worldwide, even rare adverse events become clinically significant at scale. While GLP-1 agonists are generally cardiovascular-protective, this case adds to limited reports of thrombotic complications, particularly relevant for the growing population of kidney transplant and dialysis patients being prescribed these drugs for diabetes and obesity management.","specificNumbers":"","methodology":"Single patient case report documenting the clinical presentation, diagnostic workup (including venous and arterial Doppler ultrasound and comprehensive thrombophilia testing), treatment course, and follow-up outcome of a renal transplant patient who developed extensive AV fistula thrombosis temporally associated with GLP-1 agonist dose escalation.","limitations":"Single case report — the lowest level of clinical evidence. Causation cannot be definitively established from temporal association alone. The patient had multiple risk factors for thrombosis (renal transplant, immunosuppression, AV fistula). The specific GLP-1 agonist and dose are not named in the abstract. Dehydration from reduced oral intake on GLP-1 therapy (a plausible contributing mechanism) is not discussed in the abstract."},{"rthcId":"RPEP-12673","title":"Proteomic analysis of the human amniotic mesenchymal stromal cell secretome by integrated approaches via filter-aided sample preparation.","authors":"Muntiu, Alexandra; Papait, Andrea; Vincenzoni, Federica; Rossetti, Diana Valeria; Romele, Pietro; Cargnoni, Anna; Silini, Antonietta; Parolini, Ornella; Desiderio, Claudia","year":2025,"journal":"Journal of proteomics, 310, 105339","doi":"10.1016/j.jprot.2024.105339","pmid":"39448028","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12674","title":"Synthesis and Characterization of Transferrin and Cell-Penetrating Peptide-Functionalized Liposomal Nanoparticles to Deliver Plasmid ApoE2 In Vitro and In Vivo in Mice.","authors":"Muolokwu, Chinenye Edith; Gothwal, Avinash; Kanekiyo, Takahisa; Singh, Jagdish","year":2025,"journal":"Molecular pharmaceutics, 22(1), 229-241","doi":"10.1021/acs.molpharmaceut.4c00870","pmid":"39665408","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12675","title":"Qualitative and Quantitative Analyses of Noninvasive Diagnosis of Insulinoma Using [18F]FB(ePEG12)12-Exendin-4 PET/CT.","authors":"Murakami, Takaaki; Yoshida, Hayao; Sakaki, Kentaro; Otani, Daisuke; Kawai Miyake, Kanae; Shimizu, Yoichi; Fujimoto, Hiroyuki; Yabe, Daisuke; Nakamoto, Yuji; Inagaki, Nobuya","year":2025,"journal":"The Journal of clinical endocrinology and metabolism, 111(1), 209-217","doi":"10.1210/clinem/dgaf253","pmid":"40391925","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"18F-exendin-4 PET/CT achieved 100% sensitivity for insulinoma detection in 12 patients, significantly outperforming CT (83%), MRI (63%), endoscopic ultrasonography (90%), and selective arterial calcium stimulation (89%). The peptide-based probe showed significantly higher uptake in tumor tissue than surrounding pancreatic tissue. All 12 lesions were surgically confirmed as insulinomas, and all patients achieved complete resolution of hypoglycemia after resection.","whyItMatters":"Insulinomas can be life-threatening but curable with surgery — if they can be located. Current imaging misses up to 37% of cases (MRI) or requires invasive procedures. This GLP-1 peptide-based imaging probe offers a noninvasive, highly sensitive alternative that could become the gold standard for preoperative insulinoma localization.","specificNumbers":"n=12 · 100% sensitivity (18F-exendin-4 PET/CT) · CT: 83% · MRI: 63% · endoscopic ultrasound: 90% · selective arterial calcium stimulation: 89% · scans at 60 and 120 min post-injection · all lesions surgically confirmed","methodology":"Prospective single-center phase 2 clinical trial. Twelve patients with biochemically confirmed hyperinsulinemic hypoglycemia underwent 18F-exendin-4 PET/CT with scans at 60 and 120 minutes post-injection. Results were compared to conventional imaging (CT, MRI, endoscopic ultrasound, selective arterial calcium stimulation) and verified by surgical pathology.","limitations":"Very small sample of only 12 patients from a single center. As an interim report from an ongoing phase 2 trial, the final results may differ. The 100% sensitivity in such a small cohort may not hold in larger populations. Specificity data (false positive rate) was not explicitly reported."},{"rthcId":"RPEP-12676","title":"Immune and Vascular Function in Cardiometabolic Disorders: Interplay With Sex Differences and Impact on Incretin Therapy.","authors":"Muralikrishnan, Anirudh Subramanian; Biasin, Valentina; Zabini, Diana; Osto, Elena","year":2025,"journal":"Acta physiologica (Oxford, England), 241(9), e70091","doi":"10.1111/apha.70091","pmid":"40838278","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12677","title":"Role of Gastric Point-of-Care Ultrasound in Perioperative Management of Semaglutide.","authors":"Muranaka, Mehana O; Nguyen, Tony H; Wang, Annie T; Cordero, Justin; Yang, Su-Jau; Felix, Jasmine; Nguyen, Jennifer L; Carré, Antoine L; Chu, Michael W","year":2025,"journal":"Cureus, 17(6), e85791","doi":"10.7759/cureus.85791","pmid":"40656422","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 25 patients who took weekly semaglutide less than 7 days before surgery:\n- 20 patients (80%) had empty stomachs on ultrasound and proceeded without complications\n- 5 patients (20%) had residual gastric contents despite adequate NPO (fasting) status and were rescheduled\n- Semaglutide taken 1-3 days before surgery was significantly associated with residual gastric contents compared to 4-6 days before (p = 0.02)\n- No postoperative aspiration complications occurred in patients who proceeded after clear ultrasound","whyItMatters":"With millions of people now taking GLP-1 drugs like semaglutide, anesthesiologists face a growing challenge: these drugs delay stomach emptying, meaning standard fasting guidelines may not ensure a safe empty stomach before surgery. This study provides a practical solution — bedside ultrasound — and identifies a timing threshold (4+ days before surgery) that may reduce aspiration risk while avoiding unnecessary surgical cancellations.","specificNumbers":"","methodology":"Prospective pilot study from July 2023 to February 2024. Patients who took their last weekly semaglutide dose less than 7 days before elective surgery underwent preoperative gastric point-of-care ultrasound. Those with empty stomachs proceeded; those with residual contents were rescheduled. Demographics, dosage, timing, fasting duration, and outcomes were recorded.","limitations":"Very small sample size (n=25) limits the generalizability of findings. This was a single-center pilot study without a control group. Only semaglutide was studied; other GLP-1 drugs with different half-lives may have different timing profiles. The study cannot establish what NPO duration would be sufficient without ultrasound verification, and the 1-3 day vs 4-6 day threshold needs validation in larger cohorts."},{"rthcId":"RPEP-12678","title":"Intestinal fructose metabolism triggers a glucagon-like peptide-1-β-cell axis to prevent post-fructose hyperglycaemia.","authors":"Murao, Naoya; Seino, Yusuke; Morikawa, Risa; Hidaka, Shihomi; Haraguchi, Takuya; Tomatsu, Eisuke; Habara, Mutsumi; Ohno, Tamio; Yokoi, Norihide; Harada, Norio; Hayashi, Yoshitaka; Yamada, Yuichiro; Suzuki, Atsushi","year":2025,"journal":"The Journal of physiology, 603(22), 6833-6858","doi":"10.1113/JP289067","pmid":"41129467","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12679","title":"Neuropeptide Y Y1 receptor localization in mouse brain tissue revealed by an antibody with \"hard specificity criterion\".","authors":"Murase, Shin-Ichi","year":2025,"journal":"Naunyn-Schmiedeberg's archives of pharmacology","doi":"10.1007/s00210-025-04625-7","pmid":"41152611","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12680","title":"Association between urinary sodium-to-potassium ratio and BNP in a general population without antihypertensive treatment and cardiovascular diseases: the Ohasama study.","authors":"Muroya, Tomoko; Satoh, Michihiro; Metoki, Hirohito; Nakayama, Shingo; Hirose, Takuo; Murakami, Takahisa; Tatsumi, Yukako; Inoue, Ryusuke; Tsubota-Utsugi, Megumi; Hara, Azusa; Kogure, Mana; Nakaya, Naoki; Asayama, Kei; Nomura, Kyoko; Kikuya, Masahiro; Hozawa, Atsushi; Ohkubo, Takayoshi","year":2025,"journal":"Hypertension research : official journal of the Japanese Society of Hypertension, 48(9), 2292-2302","doi":"10.1038/s41440-025-02266-0","pmid":"40579543","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12681","title":"In silico investigations of albumin-GLP-1 receptor agonist complexes for diabetes drug delivery applications.","authors":"Murphy, Gillian; Cheung, David; Fitzgerald, Michael; Pandit, Abhay","year":2025,"journal":"Computational and structural biotechnology journal, 27, 4936-4942","doi":"10.1016/j.csbj.2025.11.007","pmid":"41321995","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12682","title":"Real-world use of liraglutide for weight management according to label in the United Kingdom: A cohort study using the Clinical Practice Research Datalink primary care databases.","authors":"Murray-Thomas, Tarita; Dcruz, John M; Harder-Lauridsen, Nina M; Olsen, Anne H; Williams, Rachael; Major-Pedersen, Atheline","year":2025,"journal":"Diabetes, obesity & metabolism, 27(7), 3705-3713","doi":"10.1111/dom.16393","pmid":"40292833","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12683","title":"Characterization of glucagon-like peptide-1 (GLP-1) agonist exposures reported to a single United States poison center.","authors":"Muschler, Karen; Muschalek, Rachael; Hoyte, Christopher","year":2025,"journal":"Clinical toxicology (Philadelphia, Pa.), 63(2), 133-136","doi":"10.1080/15563650.2024.2444642","pmid":"39803696","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12684","title":"Investigation of Thyroid Disorders in Women with Diabetes in the United Arab Emirates: A Retrospective Cross-Sectional Study.","authors":"Mussa, Bashair M; Saheb Sharif-Askari, Narjes; Sulaiman, Nabil; Abusnana, Salah","year":2025,"journal":"Women's health reports (New Rochelle, N.Y.), 6(1), 161-168","doi":"10.1089/whr.2024.0136","pmid":"40130034","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12685","title":"Transforming growth factor β-2 is rhythmically expressed in both WT and BMAL1-deficient hypothalamic neurons and regulates neuropeptide Y: Disruption by palmitate.","authors":"Mustafa, Aws F; He, Wenyuan; Belsham, Denise D","year":2025,"journal":"Molecular and cellular endocrinology, 595, 112411","doi":"10.1016/j.mce.2024.112411","pmid":"39522861","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12686","title":"Influence of Combination Therapy with Dulaglutide or Liraglutide and SGLT2 Inhibitors on Renal Outcomes in Patients with Type 2 Diabetes: A Post-hoc Analysis of the RECAP Study.","authors":"Muta, Yoshimi; Kobayashi, Kazuo; Toyoda, Masao; Tsukamoto, Shunichiro; Tsuriya, Daisuke; Takashi, Yuichi; Yokomizo, Hisashi; Takeshita, Kei; Hashimoto, Takuya; Kimura, Moritsugu; Tamura, Kouichi; Kanasaki, Keizo; Kawanami, Daiji","year":2025,"journal":"The Tokai journal of experimental and clinical medicine, 50(1), 1-9","doi":null,"pmid":"40105226","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12687","title":"Sex Differences in Renal Outcomes and Metabolic Markers by Combination Therapy with SGLT2 Inhibitors and GLP-1 Receptor Agonists in Individuals with Type 2 Diabetes: A Post-Hoc Analysis of the RECAP Study.","authors":"Muta, Yoshimi; Kobayashi, Kazuo; Toyoda, Masao; Sotozawa, Mari; Chiba, Kyoji; Senda, Yuki; Hideshima, Saki; Takashi, Yuichi; Yokomizo, Hisashi; Hashimoto, Takuya; Takeshita, Kei; Tsukamoto, Shunichiro; Yomota, Miwako; Ota, Miwa; Tone, Atsuhito; Kimura, Moritsugu; Matsushita, Takaya; Suzuki, Daisuke; Murata, Takashi; Tsuriya, Daisuke; Tamura, Kouichi; Kanasaki, Keizo; Kawanami, Daiji","year":2025,"journal":"JMA journal, 8(4), 1269-1275","doi":"10.31662/jmaj.2025-0224","pmid":"41220513","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12688","title":"Giant right atrial myxoma complicated with massive pulmonary embolism and right-sided heart failure: a case report.","authors":"Mutailifu, Duolikun; Aini, Abudousaimi; Maimaitiaili, Abudunaibi","year":2025,"journal":"AME case reports, 9, 41","doi":"10.21037/acr-24-145","pmid":"40330942","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12689","title":"Snake Venom Compounds: A New Frontier in the Battle Against Antibiotic-Resistant Infections.","authors":"Muttiah, Barathan; Hanafiah, Alfizah","year":2025,"journal":"Toxins, 17(5)","doi":"10.3390/toxins17050221","pmid":"40423304","tags":["antimicrobial-peptides","venom-peptides","antibiotic-resistance"],"studyType":"Review","evidenceStrength":"Preliminary","keyFinding":"Snake venoms contain a diverse arsenal of bioactive peptides and proteins that kill bacteria through multiple mechanisms: punching holes in cell membranes, enzymatically degrading microbial structures, generating oxidative stress, breaking up biofilms, and modulating the immune system. These compounds show broad-spectrum activity against drug-resistant bacteria in lab settings.\n\nThe review also highlights a newer discovery — snake venom-derived extracellular vesicles (SVEVs) — tiny membrane-bound packages that protect venom compounds from degradation and improve their delivery to target sites. Advanced delivery strategies including PEGylation, liposomes, hydrogels, microneedle patches, and nanoparticles are being developed to reduce the toxicity of these venom compounds while preserving their antimicrobial potency.","whyItMatters":"With antibiotic resistance projected to cause millions of deaths annually by 2050, the search for alternative antimicrobials has become urgent. Snake venom represents a largely untapped natural pharmacy — millions of years of evolution have produced peptides specifically designed to kill microorganisms. The key challenge is separating the antimicrobial activity from the toxic effects, and modern delivery technologies are making this increasingly feasible.","specificNumbers":"Not applicable (narrative review covering multiple venom compound classes and delivery strategies)","methodology":"This is a narrative review published in Toxins that synthesizes research on snake venom-derived antimicrobial compounds, their mechanisms of action, delivery technologies (PEGylation, liposomes, hydrogels, microneedle patches, nanoparticles), and the emerging role of snake venom extracellular vesicles in therapeutic delivery.","limitations":"As the review itself acknowledges, most antimicrobial activity data for snake venom compounds comes from in vitro (lab dish) studies with limited translational relevance. Long-term safety in animals or humans is largely unexplored. Venom compounds carry inherent toxicity risks that delivery technologies must overcome. Manufacturing these complex biological molecules at pharmaceutical scale remains a major hurdle. The field is in its early stages with no snake venom-derived antimicrobials currently in clinical trials."},{"rthcId":"RPEP-12690","title":"Metabolic Signalling Peptides and Their Relation to Clinical and Demographic Characteristics in Acute and Recovered Females with Anorexia Nervosa.","authors":"Mutwalli, Hiba; Keeler, Johanna L; Chung, Raymond; Dalton, Bethan; Patsalos, Olivia; Hodsoll, John; Schmidt, Ulrike; Breen, Gerome; Treasure, Janet; Himmerich, Hubertus","year":2025,"journal":"Nutrients, 17(8)","doi":"10.3390/nu17081341","pmid":"40284205","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12691","title":"Systematic Review and Meta-Analysis of Liraglutide Treatment in Children Who Are Overweight or Obese: A Therapeutic Paradigm Shift?","authors":"Muñoz Rossi, Felipe A; Aristizábal, Edison A; Saleh, Kassen; Sánchez, Donovan A; Quinapanta Castro, Néstor Israel; Coronel, Jonathan; Villota, Lina A; Gonzalez, Juan D; Ibarra, David A; Ricardo Ossio, Gina Paola","year":2025,"journal":"Cureus, 17(5), e83738","doi":"10.7759/cureus.83738","pmid":"40486450","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12692","title":"A Self-Assembling Peptide with Nanoparticle-to-Fibril Transformation Exhibits Multimodal Antimicrobial Activity through Membrane Disruption and Quorum-Sensing Inhibition.","authors":"Mwangi, James; Asmamaw, Demeke; Yang, Min; Tadese, Dawit Adisu; Michira, Brenda B; Wang, Yi; Zhou, Sheng-Wen; Wang, Gan; Wang, Ziyi; Lu, Qiu-Min; Lai, Ren","year":2025,"journal":"Small (Weinheim an der Bergstrasse, Germany), 21(44), e07573","doi":"10.1002/smll.202507573","pmid":"40965309","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12693","title":"Rate of Age-Related Macular Degeneration in Patients Prescribed Glucagon-Like Peptide-1 Receptor Agonists or Other Weight Loss Therapies.","authors":"Myers, Walter K; Heath, Garrett; Rohrer, Bärbel","year":2025,"journal":"Ophthalmology. Retina","doi":"10.1016/j.oret.2025.12.016","pmid":"41453515","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In a propensity-matched retrospective study of 20,959 patients per group, GLP-1 receptor agonists were associated with a significantly lower hazard of nonexudative AMD (HR 0.47, 95% CI 0.28–0.78) and any AMD (HR 0.61, 95% CI 0.43–0.85) compared to other weight loss pharmacotherapies.\n\nThe difference for exudative (wet) AMD alone was not statistically significant (HR 0.63, 95% CI 0.30–1.32). Importantly, BMI and hemoglobin A1c trajectories were similar between the two groups over follow-up, suggesting the protective association is not simply driven by greater weight loss or metabolic improvement.","whyItMatters":"Age-related macular degeneration is the leading cause of irreversible vision loss in older adults, and treatment options for the dry form are extremely limited. If GLP-1 drugs genuinely reduce AMD risk through mechanisms beyond weight loss — possibly through anti-inflammatory or neuroprotective effects — it could represent an unexpected bonus for the millions already taking these medications and a new avenue for AMD prevention research.","specificNumbers":"","methodology":"This was a retrospective cohort study using de-identified data from the TriNetX Research Network (June 2021–October 2025). Researchers identified non-diabetic adults aged 50+ prescribed either GLP-1 receptor agonists or other weight loss drugs, requiring at least two prescriptions six months apart. After 1:1 propensity score matching on demographics, AMD risk factors, and access to eye care, 20,959 patients remained in each cohort. Outcomes were analyzed using Cox proportional hazards models.","limitations":"This is a retrospective observational study, so it cannot prove causation — only association. The TriNetX database relies on diagnostic codes, which may miss early or undiagnosed AMD. The study excluded diabetic patients, so findings may not apply to those with diabetes. Follow-up duration was limited, and exudative AMD results were not statistically significant, possibly due to its lower incidence. There may be unmeasured confounders despite propensity matching."},{"rthcId":"RPEP-12694","title":"Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 administration to Long-Evans rats has interactive effects with sex and diet on anxiety-related feeding behaviors and specific endocrine outcomes.","authors":"Myles, Elizabeth M; O'Leary, M Elizabeth; Romkey, Isaac D; Hamm, Sara I; Dauphinee, Laura; Piano, Amanda; Bronner, Stéphane; Perrot, Tara S","year":2025,"journal":"Physiology & behavior, 300, 115030","doi":"10.1016/j.physbeh.2025.115030","pmid":"40664306","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Cerebiome probiotic attenuated increased calorie intake in Western-diet-fed rats. Probiotic standard-diet males showed reduced anxiety in the novelty-suppressed feeding task. Probiotic rats overall had more feeding bouts in the center of the open field (suggesting less anxiety about eating in a novel environment). Probiotic administration increased adrenal neuropeptide Y (NPY) expression regardless of diet or sex. Plasma leptin was increased with Western diet; plasma ghrelin was elevated in standard-diet females. Female rats had higher adrenal glucocorticoid receptor expression than males. Effects were sex- and diet-dependent, highlighting the importance of studying both variables.","whyItMatters":"The gut-brain axis — how gut bacteria influence brain function — is one of the most active areas of neuroscience research. This study connects probiotics to specific peptide hormone changes (NPY, ghrelin, leptin) that regulate both anxiety and appetite. Understanding these interactions could inform probiotic-based interventions for anxiety, stress eating, and metabolic disorders, especially given the sex-specific effects that highlight the need for personalized approaches.","specificNumbers":"","methodology":"80 male and female Long-Evans rats were born to dams receiving probiotic or placebo during gestation and lactation, then continued on their respective treatments. Groups received either standard diet or a Western diet (D12079B formulation). Behavioral testing included the novelty-suppressed feeding task after 24-hour fasting. Adrenal glands were analyzed for neuropeptide Y and glucocorticoid receptor expression. Plasma leptin and ghrelin were measured at sacrifice.","limitations":"This is a rat study, and probiotic effects may not translate directly to humans. The rats received probiotics from gestation through adulthood, making it unclear whether the effects are developmental or ongoing. Only two probiotic strains were tested in combination, so individual strain contributions can't be determined. Adrenal NPY expression was measured, not brain NPY, which may have different significance. The Western diet used is one specific formulation and may not represent all unhealthy diets."},{"rthcId":"RPEP-12695","title":"Effects of Collagen Supplements on Skin Aging: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.","authors":"Myung, Seung-Kwon; Park, Yunseo","year":2025,"journal":"The American journal of medicine, 138(9), 1264-1277","doi":"10.1016/j.amjmed.2025.04.034","pmid":"40324552","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across all 23 RCTs (n=1,474), collagen supplements appeared to significantly improve skin hydration, elasticity, and wrinkles. However, subgroup analysis by funding source revealed that only pharmaceutical/supplement company-funded studies showed significant effects — independently funded studies showed no benefit in any category. Similarly, high-quality studies showed no significant effect across all skin measures, while low-quality studies showed improvement only in elasticity. The authors concluded there is no clinical evidence to support collagen supplements for skin aging.","whyItMatters":"The collagen supplement market is worth billions of dollars and growing rapidly, largely based on clinical trials showing skin benefits. This meta-analysis reveals that those positive results are almost entirely driven by industry-funded research and low-quality study designs. It's a striking example of how funding bias and study quality can create a misleading evidence base, and it challenges consumers and clinicians to reconsider the evidence for a very popular supplement.","specificNumbers":"","methodology":"Systematic review and meta-analysis of 23 randomized controlled trials (1,474 total participants) identified through PubMed, Embase, and Cochrane Library searches through June 2024. The key innovation was stratifying results by funding source (industry vs. independent) and study quality (high vs. low), which revealed that the overall positive results were driven entirely by industry-funded and lower-quality studies.","limitations":"The meta-analysis is limited by the quality and heterogeneity of the underlying trials. Different collagen types, sources, doses, and durations were pooled together. The subgroup of independently funded studies was likely smaller than the industry-funded group, potentially limiting statistical power to detect real effects. The analysis assessed published outcomes only and could not account for unpublished negative industry trials."},{"rthcId":"RPEP-12696","title":"Exploring the impact of the host defense peptide Pap12-6 on immune response and epithelial integrity in chicken-derived ileal explant cultures.","authors":"Márton, Rege Anna; Tráj, Patrik; Mackei, Máté; Sebők, Csilla; Vörösházi, Júlia; Kemény, Ágnes; Kámán-Tóth, Evelin; Horváth, Dávid Géza; Molnár-Nagy, Viviána; Neogrády, Zsuzsanna; Mátis, Gábor","year":2025,"journal":"Poultry science, 104(8), 105376","doi":"10.1016/j.psj.2025.105376","pmid":"40466266","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12697","title":"Improving the Activity and Selectivity of a Scorpion-Derived Peptide, A3a, against Acinetobacter baumannii through Rational Design.","authors":"Möller, Dalton S; van der Walt, Mandelie; Oosthuizen, Carel; Serian, Miruna; Serem, June C; Lorenz, Christian D; Mason, A James; Bester, Megan J; Gaspar, Anabella R M","year":2025,"journal":"ACS omega, 10(5), 4699-4710","doi":"10.1021/acsomega.4c09593","pmid":"39959037","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12698","title":"GLP-1R Agonists for Weight Loss in Psychiatric Disorders: A Systematic Review and Meta-analysis.","authors":"Müller Alves, Klara; Teixeira da Silva, Manoela; Kramer, Caroline Kaercher; Viana, Luciana Verçoza","year":2025,"journal":"Journal of the Endocrine Society, 9(12), bvaf150","doi":"10.1210/jendso/bvaf150","pmid":"41230025","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12699","title":"Smart-AMPs: Decorated Nanostructured Lipid Carriers for Improved Efficacy of Antimicrobial Peptides in Chronically Infected Burn Wounds.","authors":"Müller, Daniela; Nallbati, Laura; Keck, Cornelia M","year":2025,"journal":"Pharmaceutics, 17(8)","doi":"10.3390/pharmaceutics17081039","pmid":"40871060","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12700","title":"SGLT2 Inhibitor and GLP-1 Receptor Agonist Prescriptions in Newly Diagnosed Type 2 Diabetes Patients With Cardiorenal Risks: A Cross-Sectional Study.","authors":"Müller, Frank; Bouthillier, Michael J; Alshaarawy, Omayma; Azhary, Hend; Holman, Harland T","year":2025,"journal":"Journal of diabetes research, 2025, 6656982","doi":"10.1155/jdr/6656982","pmid":"41220901","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12701","title":"Obesity as a Multifactorial Chronic Disease: Molecular Mechanisms, Systemic Impact, and Emerging Digital Interventions.","authors":"Młynarska, Ewelina; Bojdo, Kinga; Bulicz, Anna; Frankenstein, Hanna; Gąsior, Magdalena; Kustosik, Natalia; Rysz, Jacek; Franczyk, Beata","year":2025,"journal":"Current issues in molecular biology, 47(10)","doi":"10.3390/cimb47100787","pmid":"41150735","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Obesity pathophysiology involves insulin resistance, dyslipidemia, chronic low-grade inflammation, and neuroendocrine dysregulation of appetite. Gut-derived peptide hormones (leptin, ghrelin, GLP-1, PYY, CCK) are pivotal regulators of appetite and weight. Beyond caloric excess, genetic predisposition, epigenetic modifications, gut microbiota dysbiosis, endocrine-disrupting chemicals, circadian misalignment, and prenatal/intergenerational influences are all critical determinants. Advances in molecular profiling and metabolic phenotyping are enabling precise risk stratification and personalized treatment selection.","whyItMatters":"Obesity is the most prevalent chronic disease globally and drives type 2 diabetes, cardiovascular disease, cancer, and many other conditions. Understanding obesity as a complex biological disease — not just a behavioral problem — is essential for developing effective treatments and reducing stigma. The review places peptide hormone therapies (especially GLP-1 drugs) in the broader context of obesity biology, showing why they work and where future treatments may emerge.","specificNumbers":"","methodology":"Comprehensive narrative review synthesizing contemporary evidence across molecular biology, genetics, endocrinology, gastroenterology, epidemiology, and digital health. Covers the biological basis, systemic consequences, preventive strategies, and therapeutic modalities of obesity.","limitations":"This is a very broad narrative review covering numerous topics at a high level. Individual claims about genetic, epigenetic, and microbiome contributions vary greatly in their strength of evidence. The review doesn't systematically evaluate the quality of evidence for each mechanism. Some discussed therapies (gene therapy, AI platforms) are still largely experimental. The breadth may sacrifice depth on any single topic."},{"rthcId":"RPEP-12702","title":"Effectiveness and Safety of CGRP-Targeted Therapies Combined with Lifestyle Modifications for Chronic Migraine in Korean Pediatric Patients: A Retrospective Study.","authors":"Na, Ji-Hoon; Jeon, Hayoon; Shim, Ji-Eun; Lee, Hyunjoo; Lee, Young-Mock","year":2025,"journal":"Brain sciences, 15(5)","doi":"10.3390/brainsci15050493","pmid":"40426664","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 10 pediatric chronic migraine patients who had failed at least 2 prior preventive therapies, CGRP monoclonal antibodies or antagonists combined with structured lifestyle modifications produced significant improvements over 12 months:\n\n- Migraine frequency decreased from a median of 26.5 to 14 days per month (statistically significant)\n- Acute analgesic use dropped from 14 to 5 days per month (statistically significant)\n- Disability scores improved significantly (p=0.037)\n\nAll patients had severe baseline burden (PedMIDAS score ≥30, ≥8 migraine days per month), making these reductions clinically meaningful for this difficult-to-treat population.","whyItMatters":"CGRP-targeted therapies have transformed adult migraine care, but their use in children remains largely uncharted territory. Pediatric chronic migraine is especially debilitating — it affects school attendance, social development, and quality of life. This study provides early evidence that these peptide-targeting treatments are safe and effective in young patients, potentially opening a new treatment avenue for children who haven't responded to standard medications.","specificNumbers":"","methodology":"This was a retrospective study of 10 pediatric chronic migraine patients treated at Gangnam Severance Hospital in Korea from 2021 to 2024. Inclusion criteria required a PedMIDAS disability score of 30 or higher, failure of more than 2 preventive therapies, and at least 8 migraine days per month. Patients received CGRP monoclonal antibodies or antagonists alongside structured sleep, dietary, and exercise interventions. Outcomes including migraine frequency, neuropsychological measures, and lifestyle adherence were tracked over 12 months.","limitations":"The sample size of only 10 patients is very small, limiting statistical power and generalizability. The retrospective design means there was no control group — improvements could partly reflect the lifestyle modifications, natural disease fluctuation, or placebo effects. The study was conducted at a single Korean hospital, and results may not generalize to other populations. The abstract also appears to have incomplete p-values, suggesting possible formatting issues in the original publication."},{"rthcId":"RPEP-12703","title":"In the Eye of Controversy: A Deeper Look Into the Impact of Glucagon-like Peptide-1 Receptor Agonists on Diabetic Retinopathy and Nonarteritic Anterior Ischemic Optic Neuropathy.","authors":"Nadeem, Nadia; Al Issa, Raghad Mazin; Shah, Asnin; Wardeh, Rahaf; Rashid, Fauzia; Abdelgadir, Elamin Ibrahim; Bashier, Alaaeldin","year":2025,"journal":"Canadian journal of diabetes, 49(7), 401-410","doi":"10.1016/j.jcjd.2025.07.002","pmid":"40712696","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review reached several key conclusions about GLP-1 receptor agonists and eye health:\n\n1. Preclinical studies hint at possible retinal protective effects of GLP-1 agonists\n2. Clinical cases of retinopathy worsening after GLP-1RA use are likely due to rapid reduction in glycated hemoglobin (HbA1c) levels rather than the drug's mechanism of action — a phenomenon known as 'early worsening' that occurs with any treatment that rapidly improves blood sugar control\n3. Evidence linking semaglutide specifically to nonarteritic anterior ischemic optic neuropathy (NAION) remains inconclusive and limited by methodological constraints\n4. Large-scale, well-designed studies are needed to clarify both potential associations and guide clinical practice","whyItMatters":"With tens of millions of people now taking GLP-1 drugs, even a small increase in eye complication risk could affect enormous numbers of patients. Many people taking these drugs for diabetes already have retinopathy or are at risk for it. Clinicians need clear guidance on whether to screen more aggressively, adjust dosing speed, or warn patients about eye risks. This review helps separate genuine safety signals from the expected consequences of rapid blood sugar improvement.","specificNumbers":"","methodology":"This is a narrative review synthesizing relevant publications including meta-analyses, randomized controlled trials, post hoc analyses, and preclinical in vitro and in vivo research. The literature search used WorldCat Discovery, PubMed, and Google Scholar databases. The review evaluated both the diabetic retinopathy and NAION associations separately.","limitations":"As a narrative review, this does not use systematic methodology or quantitative meta-analysis. The evidence base for both associations is relatively limited — most retinopathy data comes from post hoc analyses of trials not designed to study eye outcomes, and NAION evidence is largely from case reports and observational studies with significant confounders. The review cannot definitively rule out a causal relationship for either condition. Publication bias may affect the available literature in both directions."},{"rthcId":"RPEP-12704","title":"Plasma metabolomics identifies signatures that distinguish heart failure with reduced and preserved ejection fraction.","authors":"Naeem, Fawaz; Leone, Teresa C; Petucci, Christopher; Shoffler, Clarissa; Kodihalli, Ravindra C; Hidalgo, Tiffany; Tow-Keogh, Cheryl; Mancuso, Jessica; Tzameli, Iphigenia; Bennett, Donald; Groarke, John D; Roth Flach, Rachel J; Rader, Daniel J; Kelly, Daniel P","year":2025,"journal":"ESC heart failure, 12(4), 2803-2813","doi":"10.1002/ehf2.15285","pmid":"40232999","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12705","title":"NeoPAIR-T: Functional Mapping of Neoantigen-TCR Pairs Using a CRISPR-Engineered Jurkat Reporter System.","authors":"Nagaoka, Koji; Kobayashi, Yukari; Kakimi, Kazuhiro","year":2025,"journal":"Cells, 14(22)","doi":"10.3390/cells14221789","pmid":"41294842","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"NeoPAIR-T successfully identified two functional neoantigen-TCR pairs from lung cancer samples out of 63 candidate peptides and 8 TCR clonotypes. The system uses CRISPR-engineered Jurkat reporter T cells with luciferase/eGFP dual readout and autologous antigen-presenting cells transfected with tandem minigenes encoding predicted neoantigens. The validated pairs showed functional binding with EC50 values ranging from 10⁻⁹·² to 10⁻⁶·⁷ M, confirmed by peptide assays. Key innovations include TCRα-knockout with targeted knock-in to prevent receptor mispairing, and the ability to test multiple reporter clones in parallel against the same antigen-presenting cells.","whyItMatters":"Personalized cancer vaccines and adoptive T cell therapies need to know exactly which mutant peptides a patient's immune system can target, but current methods are slow, expensive, and unreliable. NeoPAIR-T offers a streamlined approach that could accelerate the development of personalized immunotherapies by making neoantigen-TCR matching more efficient and scalable.","specificNumbers":"63 candidate neoantigen peptides · 3 tandem minigenes · 8 TCR clonotypes · 2 functional neoantigen-TCR pairs · EC50: 10⁻⁹·² to 10⁻⁶·⁷ M","methodology":"The researchers engineered Jurkat T cells with a dual luciferase/eGFP reporter system that activates when the T cell receptor is triggered. They used CRISPR to knock out the native TCR alpha chain and knock in candidate TCRs at a specific location to prevent mispairing. Candidate neoantigen peptides were predicted from whole-exome and RNA sequencing of lung cancer samples, then assembled into tandem minigene constructs expressed in immortalized autologous antigen-presenting cells. Multiple reporter T cell clones were co-cultured with antigen-presenting cells in parallel to identify functional matches, which were then validated using individual peptide assays.","limitations":"The study demonstrated the system using samples from a single lung cancer case, so broader applicability across cancer types and patient populations is not yet established. The approach still depends on computational prediction of candidate neoantigens, which has inherent uncertainty. Only 2 of 63 candidates were confirmed as functional pairs, reflecting the known difficulty of neoantigen prediction rather than a limitation of the assay itself."},{"rthcId":"RPEP-12706","title":"Weighing the Risks: Small Bowel Obstruction Associated With Semaglutide Use in the Postoperative Abdomen.","authors":"Nagib, Natalie; Avila, Daniela; Partyka, Joanna; Kamyab, Armin","year":2025,"journal":"Cureus, 17(7), e88589","doi":"10.7759/cureus.88589","pmid":"40861748","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12707","title":"Improving the Quality of Two Lives by Treating Obesity.","authors":"Nagy, Norbert; Kleinová, Patrícia; Péč, Martin Jozef; Samoš, Matej; Dedinská, Ivana","year":2025,"journal":"Reports (MDPI), 8(2)","doi":"10.3390/reports8020085","pmid":"40710876","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A 63-year-old woman with grade II obesity (BMI not specified but >35 kg/m²) was initially denied as a living kidney donor. After 3 months of comprehensive treatment at a cardio-obesitology clinic — including caloric restriction, physical activity, and liraglutide — her BMI decreased to 33.4 kg/m². Subsequent evaluation confirmed no surgical contraindications. An incidental finding of hematuria led to a diagnosis of benign Alport syndrome carrier status, which without proteinuria or renal impairment did not preclude donation. She successfully donated her kidney.","whyItMatters":"Obesity is increasingly disqualifying potential living kidney donors, while organ donation demand continues to outstrip supply. This case demonstrates that GLP-1 receptor agonists can provide a faster, less invasive alternative to bariatric surgery for donor candidates who need to lose weight. This could expand the pool of eligible living donors and improve transplant outcomes.","specificNumbers":"","methodology":"This is a single case report from a cardio-obesitology clinic. The patient received a comprehensive lifestyle modification program including caloric restriction, physical activity, and pharmacological treatment with liraglutide (GLP-1 receptor agonist). BMI was tracked over a 3-month follow-up period, and standard pre-donation medical evaluations were performed.","limitations":"This is a single case report (n=1) and cannot establish generalizability. The exact starting BMI is not specified in the abstract. The 3-month timeline is short, and it's unclear whether the weight loss was maintained long-term. No comparison to bariatric surgery outcomes is provided. The specific liraglutide dose and its individual contribution versus lifestyle changes cannot be isolated."},{"rthcId":"RPEP-12708","title":"Severe Small-Bowel Obstruction in a High-Risk Patient on Long-Term Tirzepatide Therapy: A Case Report.","authors":"Nahar, Shamsun; Maybee, Nelly; Tamanna, Nowrin; Sadat, Anahita; Khanam, Farjana; Begum, Rokeya; Akther, Sume; Khan, Mishma Salsabil; Sonia, Shamsun Nahar; Hasan, Nahid","year":2025,"journal":"Cureus, 17(12), e98935","doi":"10.7759/cureus.98935","pmid":"41523550","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12709","title":"Pharmacological Profile of NCP-322, a Novel G Protein-Coupled Receptor 119 Agonist, as an Orally Active Therapeutic Agent for Type 2 Diabetes Mellitus.","authors":"Nakamura, Hideki; Endo, Tsuyoshi; Tsuda, Makoto","year":2025,"journal":"Biological & pharmaceutical bulletin, 48(1), 65-74","doi":"10.1248/bpb.b24-00737","pmid":"39894557","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12710","title":"Decline in oral function contributes to decreased activities of daily living at discharge in elderly patients with heart failure.","authors":"Nakamura, Misaki; Yamamoto, Kanako; Nozaki, Shinichi; Saeki, Takahiro; Omi, Wataru; Kato, Chieko; Inoue, Masaru; Harada, Tomoya; Sakagami, Satoru","year":2025,"journal":"PloS one, 20(5), e0323806","doi":"10.1371/journal.pone.0323806","pmid":"40435119","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12711","title":"Hemodynamic Changes After Wire Frame Occluders vs. Metal Mesh Devices for Atrial Septal Defect.","authors":"Nakashima, Mitsutaka; Takaya, Yoichi; Ejiri, Kentaro; Miki, Takashi; Nakayama, Rie; Nakagawa, Koji; Akagi, Teiji; Nakamura, Kazufumi; Yuasa, Shinsuke","year":2025,"journal":"Circulation journal : official journal of the Japanese Circulation Society, 89(7), 930-938","doi":"10.1253/circj.CJ-24-0966","pmid":"40139815","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12712","title":"Effect of iPS cell culture medium on the differentiation potential of induced cardiac tissues.","authors":"Nakashima, Yoshiki; Tsukahara, Masayoshi","year":2025,"journal":"Scientific reports, 15(1), 28301","doi":"10.1038/s41598-025-13259-x","pmid":"40754549","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12713","title":"Visible Exocytosis of the Non-Photic Signal Neuropeptide Y to the Suprachiasmatic Nucleus in Fasted Transgenic Mice Throughout Their Circadian Rhythms.","authors":"Nakazawa, Kazuo; Matsuo, Minako; Nakao, Kazuki; Nonaka, Shigenori; Numano, Rika","year":2025,"journal":"Bioengineering (Basel, Switzerland), 12(2)","doi":"10.3390/bioengineering12020192","pmid":"40001711","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Novel NPY::Venus transgenic mice were successfully generated, allowing direct visualization of neuropeptide Y secretory granules in brain tissue using confocal and super-resolution microscopy. The key finding was that the number of NPY secretory granules released onto the SCN increased during fasting conditions, providing direct visual evidence that NPY serves as a feeding-state signal to the brain's master circadian oscillator.\n\nThis establishes that NPY from the intergeniculate leaflet (IGL) neurons is actively secreted onto the SCN in response to fasting, suggesting a mechanism by which the food-entrainable oscillator communicates with the light-dependent circadian clock.","whyItMatters":"Understanding how feeding timing interacts with the circadian clock is important for metabolic health, shift work adaptation, and intermittent fasting research. This study provides the first direct visualization of how the neuropeptide NPY acts as a messenger between feeding status and the brain's master clock, opening new avenues for understanding metabolic timing disorders.","specificNumbers":"","methodology":"Researchers generated novel NPY::Venus transgenic mice expressing NPY fused to Venus fluorescent protein, enabling visualization of NPY in living tissue. SCN brain slices from these mice were examined using confocal and super-resolution microscopy to observe NPY-containing secretory granules. Granule counts were compared between fed and fasted conditions to assess changes in NPY release.","limitations":"The study was conducted in transgenic mice, and the fluorescent protein fusion to NPY could potentially affect the peptide's normal behavior or trafficking. Only fasting versus fed states were compared — intermediate feeding conditions were not tested. The study did not assess functional consequences of the increased NPY release on circadian rhythm parameters. Sample sizes and quantitative statistical analyses were not detailed in the abstract."},{"rthcId":"RPEP-12714","title":"Risk of Suicide, Hair Loss, and Aspiration with GLP1-Receptor Agonists and Other Diabetic Agents: A Real-World Pharmacovigilance Study.","authors":"Nakhla, Michael; Nair, Ambica; Balani, Prachi; Ujjawal, Aditi; Arun Kumar, Pramukh; Dasari, Mahati; Yukselen, Zeynep; Bansal, Kannu; Ganatra, Sarju; Dani, Sourbha S","year":2025,"journal":"Cardiovascular drugs and therapy, 39(6), 1331-1341","doi":"10.1007/s10557-024-07613-w","pmid":"39264502","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12715","title":"Real-World Effectiveness of Finerenone Added to SGLT2 Inhibitor and GLP-1 Receptor Agonist Therapy in Individuals with Type 2 Diabetes and Chronic Kidney Disease.","authors":"Nakhleh, Afif; Khazim, Khaled; Shehadeh, Naim","year":2025,"journal":"Journal of clinical medicine, 14(22)","doi":"10.3390/jcm14228209","pmid":"41303244","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Over a median follow-up of 27 weeks, adding finerenone to existing SGLT2 inhibitor and GLP-1 receptor agonist therapy produced an adjusted 51.3% reduction in urinary albumin-to-creatinine ratio (UACR), a key marker of kidney damage.\n\nKidney function (eGFR) remained stable during the treatment period. Serum potassium levels did not rise to dangerous levels. The albuminuria reduction was consistent across subgroups analyzed by age, sex, BMI, baseline eGFR, and baseline UACR.\n\nNotably, 94% of patients were also receiving a renin-angiotensin system inhibitor, meaning this was effectively a quadruple-therapy approach targeting multiple pathways of diabetic kidney disease.","whyItMatters":"Diabetic kidney disease is the leading cause of kidney failure worldwide. While individual medications like GLP-1 receptor agonists and SGLT2 inhibitors each provide kidney protection, this study demonstrates that stacking finerenone on top of these peptide-based and other therapies produces substantial additional benefit in real-world practice — not just in controlled clinical trials.","specificNumbers":"","methodology":"Retrospective cohort study from diabetes, endocrinology, and nephrology clinics at Maccabi Healthcare Services in Haifa, Israel. Included 51 adults with type 2 diabetes and chronic kidney disease (eGFR 25-60, UACR >300 mg/g) who had been on SGLT2 inhibitors and GLP-1 receptor agonists for at least 12 weeks before starting finerenone between August 2023 and January 2025. Outcomes were assessed at the last measurement within 26 ± 10 weeks of finerenone initiation. Multiple linear regression models were used, with prespecified subgroup analyses.","limitations":"Small sample size of only 51 patients from a single healthcare system in Israel limits generalizability. The retrospective design cannot establish causation. Some outcome data appears truncated in the abstract (p-values cut off). There was no control group of patients not receiving finerenone. The relatively short follow-up of ~6 months cannot assess long-term kidney outcomes like progression to dialysis. Selection bias is possible as these were patients already on optimal triple therapy."},{"rthcId":"RPEP-12716","title":"The efficacy of DPP IV inhibitors as adjunct therapy for patients with auto-immune Diabetes: A systematic review and meta-analysis.","authors":"Nakhoul, Laurette; Nakhoul, Tracy; Abi Azar, Maria; Harb, Frederic; Nakhoul, Nancy Fawzi","year":2025,"journal":"PloS one, 20(9), e0332191","doi":"10.1371/journal.pone.0332191","pmid":"41026724","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12717","title":"Calcitonin gene-related peptide differentially modulates intracellular calcium levels in response to depolarizing stimuli in trigeminal ganglion neurons and glial cells.","authors":"Nalley, Nicole M; Durham, Paul L","year":2025,"journal":"Neuroscience, 591, 40-51","doi":"10.1016/j.neuroscience.2025.11.004","pmid":"41207466","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12718","title":"Over-expression of Tfgd2-RsAFP2 fusion gene isolated from fenugreek and radish shows enhanced disease resistance against Alternaria blight disease caused by Alternaria alternata in transgenic pigeonpea.","authors":"Nalluri, Nirmala; Karri, Vasavirama","year":2025,"journal":"Molecular biology reports, 52(1), 383","doi":"10.1007/s11033-025-10471-w","pmid":"40210805","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12719","title":"GLP-1RA comparative effectiveness against dementia onset relative to other antidiabetic medications in a large, multi-site cohort of patients with type 2 diabetes.","authors":"Nance, Nerissa; Gilsanz, Paola; Karter, Andrew J; Finertie, Holly; Schmittdiel, Julie A; An, JaeJin; Adams, Alyce S; Oshiro, Caryn; Cassidy-Bushrow, Andrea E; Krahe-Dombrowski, Sarah; Yassin, Maher; Lin, Sharon; Izadian, Keanu; O'Connor, Patrick J; Neugebauer, Romain","year":2025,"journal":"Alzheimer's & dementia : the journal of the Alzheimer's Association, 21(9), e70621","doi":"10.1002/alz.70621","pmid":"40952016","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12720","title":"Socioeconomic Factors Associated With Migraine Medication Prescription at a Tertiary Headache Center: A Retrospective Cohort Analysis.","authors":"Nandyala, Arathi S; Tan, Kenneth; Africk, Benjamin; Graber-Naidich, Anna; Zhang, Niushen; He, Zihuai; Moskatel, Leon S","year":2025,"journal":"Neurology. Clinical practice, 15(5), e200517","doi":"10.1212/CPJ.0000000000200517","pmid":"40741480","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12721","title":"Therapeutic Efficacy of Intranasal N-Acetyl-L-Cysteine with Cell-Penetrating Peptide-Modified Polymer Micelles on Neuropathic Pain in Partial Sciatic Nerve Ligation Mice.","authors":"Nango, Hiroshi; Takahashi, Ai; Suzuki, Naoto; Kurano, Takumi; Sakamoto, Saia; Nagatomo, Taiki; Suzuki, Toyofumi; Kanazawa, Takanori; Kosuge, Yasuhiro; Miyagishi, Hiroko","year":2025,"journal":"Pharmaceutics, 17(1)","doi":"10.3390/pharmaceutics17010044","pmid":"39861692","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12722","title":"Population-level impact of semaglutide 2.4 mg in patients with obesity or overweight and cardiovascular disease: A modelling study based on the SELECT trial.","authors":"Nanna, Michael G; Doan, Quan V; Fabricatore, Anthony; Faurby, Mads; Henry, Alasdair D; Houshmand-Oeregaard, Azadeh; Levine, Alina; Navar, Ann Marie; Scassellati Sforzolini, Thomas; Toliver, Joshua C","year":2025,"journal":"Diabetes, obesity & metabolism, 27(6), 3442-3452","doi":"10.1111/dom.16370","pmid":"40183412","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12723","title":"Efficacy and Safety of Efpeglenatide in Patients With Type 2 Diabetes and Obesity: A Systematic Review.","authors":"Narayan, Neha; Vadde, Tejaswi; Sandesara, Maharshikumar; Divity, Shravani; Mamytova, Aiturgan; Tagaev, Tugolbai","year":2025,"journal":"Cureus, 17(1), e77089","doi":"10.7759/cureus.77089","pmid":"39917155","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12724","title":"Therapeutic tailored approach in patients with diabetes, cardiovascular and renal comorbidities: A cardiologist's view.","authors":"Nardi, Ermanno; Prastaro, Maria; Santoro, Ciro; Gallo, Luca; Simeoli, Luisa; Fontanarosa, Sara; Paolillo, Stefania; Gargiulo, Paola; Esposito, Giovanni; Filardi, Pasquale Perrone","year":2025,"journal":"Nutrition, metabolism, and cardiovascular diseases : NMCD, 35(9), 104033","doi":"10.1016/j.numecd.2025.104033","pmid":"40610294","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12725","title":"Upcoming drug targets for kidney protective effects in chronic kidney disease.","authors":"Nardone, Massimo; Yau, Kevin; Kugathasan, Luxcia; Odutayo, Ayodele; Mohsen, Mai; Ouimet, Jean-Philippe; Sridhar, Vikas S; Cherney, David Z I","year":2025,"journal":"Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 40(Supplement_1), i47-i58","doi":"10.1093/ndt/gfae216","pmid":"39907540","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12726","title":"Optimising Access to Care for Patients with Heart and Kidney Diseases: A World Heart Federation and International Society of Nephrology White Paper.","authors":"Narula, Jagat; Butler, Javed; Chothia, Yazied; Bannerjee, Debasish; Jarraya, Faical; Ulasi, Ifeoma; Luyckx, Valerie","year":2025,"journal":"Global heart, 20(1), 88","doi":"10.5334/gh.1460","pmid":"41079057","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12727","title":"Metabolic syndrome reduces but does not eliminate the cardioprotective effect of adaptation to hypoxia: the link with changes in the opioid system.","authors":"Naryzhnaya, Natalia V; Derkachev, Ivan A; Kurbatov, Boris K; Mukhomedzyanov, Alexander V; Kilin, Mikhail; Kan, Artur; Grab, Alexandr E; Boschenko, Alla A; Maslov, Leonid N","year":2025,"journal":"Pflugers Archiv : European journal of physiology, 478(1), 2","doi":"10.1007/s00424-025-03144-x","pmid":"41354854","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12728","title":"Imo-induced changes in gut hormones and glucose metabolism: A key to improving insulin sensitivity in type 2 diabetes.","authors":"Naseem, Sobia; Rizwan, Muhammad","year":2025,"journal":"Diabetes research and clinical practice, 226, 112285","doi":"10.1016/j.diabres.2025.112285","pmid":"40449625","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12729","title":"Prognostic Serum Calcitonin Gene-Related Peptide Level Value in Patients Following Traumatic Brain Injury.","authors":"Naseri Alavi, Seyed Ahmad; Habibi, Mohammad Amin; Rezakhah, Amir; Naseri Alavi, Seyed Hamed; Heydarian, Parichehr; Torkan, Jafar Sadegh Mohammadi; Jung, Geena; Keymakh, Margaret; Kobets, Andrew J","year":2025,"journal":"Asian journal of neurosurgery, 20(2), 285-290","doi":"10.1055/s-0044-1801783","pmid":"40485781","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12730","title":"Venom Peptides Across Asian and American Tarantulas Utilize Dual Pharmacology to Target Activation and Fast Inactivation of Voltage-Gated Sodium Channels.","authors":"Nashikwala, Amatulla S; Kotapati, Charan; Eagles, David A; Lewis, Richard J; Cardoso, Fernanda C","year":2025,"journal":"Toxins, 17(11)","doi":"10.3390/toxins17110561","pmid":"41295876","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12731","title":"Exploring Glucagon-Like Peptide-1 Receptor Agonists Usage Among Non-Diabetic Healthcare Providers: A Cross-Sectional Multi-Country Study.","authors":"Nashwan, Abdulqadir J; Abukhadijah, Hana J; Karavadi, Vidusha; Aqtam, Ibrahim; Ibraheem, Anas; Palanivelu, Prakash; Khedr, Mahmoud A; Agga, Abdulkarim O; Rehman, Obaid Ur; Fatima, Eeshal; Abu Asal, Mohammad A; Abutaima, Rana; Shaban, Marwa M; Shaban, Mostafa; Barakat, Muna; Aldosari, Nasser M; Alomari, Albara M; Aljariri, Adham A; Al-Lobaney, Nabeel F; Othman, Mutaz I; Abujaber, Ahmad A; Bastaki, Kholoud","year":2025,"journal":"Health science reports, 8(4), e70638","doi":"10.1002/hsr2.70638","pmid":"40276133","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12732","title":"Comparative outcomes of systemic diseases in people with type 2 diabetes, or obesity alone treated with and without GLP-1 receptor agonists: a retrospective cohort study from the Global Collaborative Network : Author list.","authors":"Nassar, Mahmoud; Nassar, Omar; Abosheaishaa, Hazem; Misra, Anoop","year":2025,"journal":"Journal of endocrinological investigation, 48(2), 483-497","doi":"10.1007/s40618-024-02466-4","pmid":"39302577","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In type 2 diabetes patients, GLP-1 RA treatment was associated with significantly lower incidences of multiple systemic conditions compared to non-users (over 5+ years of follow-up):\n\n- Dementia: Risk Difference -0.010 (p<0.001)\n- Alzheimer's disease: RD -0.003 (p<0.001)\n- Parkinson's disease: RD -0.002 (p<0.001)\n- Pancreatic cancer: RD -0.003 (p<0.001)\n- Systemic lupus erythematosus: RD -0.001 (p<0.001)\n- Systemic sclerosis: RD -0.000 (p<0.001)\n\nBronchial asthma showed a slight increase in risk (RD 0.002, p<0.001). Similar patterns were observed in the obesity-only cohort. Additional conditions evaluated included rheumatoid arthritis, ulcerative colitis, Crohn's disease, osteoporosis, and several cancers.","whyItMatters":"GLP-1 medications are already among the world's most prescribed drugs for diabetes and weight loss. This study suggests their benefits may extend far beyond blood sugar and weight control — potentially reducing risk of neurodegenerative diseases, autoimmune conditions, and certain cancers. If confirmed in prospective trials, these findings could reshape how clinicians weigh the benefits of GLP-1 therapy and could expand the indications for these medications.","specificNumbers":"","methodology":"Retrospective cohort study using the Global Collaborative Network accessed through the TriNetX analytics platform. Two primary groups were compared: individuals with type 2 diabetes and individuals with obesity. Each group was divided into GLP-1 RA users vs. non-users. Incidences of 10+ systemic diseases were compared over more than 5 years of follow-up. Propensity matching methods were presumably used to balance groups (standard for TriNetX studies).","limitations":"This is a retrospective observational study, which cannot prove causation. Despite the large sample size and global scope, residual confounding is a major concern — patients prescribed GLP-1 RAs may differ from non-users in unmeasured ways (health consciousness, access to care, overall health status). Some of the risk differences, while statistically significant, are small in absolute magnitude (e.g., SLE RD -0.001). The study does not differentiate between specific GLP-1 RAs or doses. Prospective randomized trials are needed to confirm these associations."},{"rthcId":"RPEP-12733","title":"Acute Pancreatitis After Initiating Dulaglutide in a Patient Previously Treated With a DPP-4 Inhibitor: Case Report From Palestine.","authors":"Nasser, Alisse; Ladadweh, Hosniyeh; Madia, Raed; Dalashi, Ahmad; Wahdan, Adnan; Alawi, Abdullah","year":2025,"journal":"Case reports in gastrointestinal medicine, 2025, 9918202","doi":"10.1155/crgm/9918202","pmid":"41355891","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12734","title":"When New Therapies Meet Old Challenges: Tirzepatide-Warfarin Interaction in A Mechanical Mitral Valve Patient.","authors":"Natale, Raffaele; Morena, Annadora; Capece, Luca Maria; Donnarumma, Sofia; Pagano, Ermenegilda; Pasanisi, Fabrizio; Santarpia, Lidia","year":2025,"journal":"European journal of case reports in internal medicine, 12(10), 005823","doi":"10.12890/2025_005823","pmid":"41064709","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12735","title":"Cardiometabolic effects of GLP-1 analogs in obese and overweight patients with preexisting cardiovascular disease: A systematic review and meta analysis of randomized controlled trials.","authors":"Natali, Lucas Destefani; de Oliveira, Luis Gustavo Menegardo Siqueira; Barbosa, Imara Correia de Queiroz; Portilho, Natanael de Paula","year":2025,"journal":"Heart & lung : the journal of critical care, 74, 174-179","doi":"10.1016/j.hrtlng.2025.07.009","pmid":"40682989","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12736","title":"Ocular Adverse Events With Semaglutide: A Systematic Review and Meta-Analysis.","authors":"Natividade, Gabriella R; Spiazzi, Bernardo F; Baumgarten, Matheus W; Bassotto, Caroline; Pereira, Afonso A; Fraga, Bruna L; Scalco, Bruno G; Mattes, Nicole R; Lavinsky, Daniel; Kramer, Caroline K; Gerchman, Fernando","year":2025,"journal":"JAMA ophthalmology, 143(9), 759-768","doi":"10.1001/jamaophthalmol.2025.2489","pmid":"40810985","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 78 randomized clinical trials with 73,640 participants, semaglutide showed no association with increased risk of eye disorders overall (OR 1.01; 95% CI 0.91–1.12) or diabetic retinopathy specifically (OR 1.04; 95% CI 0.92–1.17).\n\nHowever, semaglutide treatment was associated with significantly increased odds of nonarteritic anterior ischemic optic neuropathy (NAION), with an OR of 3.92 (95% CI 1.02–15.02). This is a rare but serious condition involving sudden loss of blood flow to the optic nerve.\n\nTrial sequential analysis confirmed sufficient sample size to rule out increased diabetic retinopathy risk, but the data were insufficient to draw definitive conclusions about the NAION association, given the rarity of this event.","whyItMatters":"Semaglutide is one of the most widely prescribed medications in the world. Early reports of potential eye problems alarmed patients and clinicians alike. This meta-analysis provides the most comprehensive safety assessment to date, reassuring patients about general eye health and diabetic retinopathy while flagging a potential rare risk (NAION) that deserves monitoring and further study.","specificNumbers":"","methodology":"The researchers conducted a systematic review and meta-analysis following standard methodology. They searched PubMed, Embase, and Cochrane Central Register through April 2025 with no date restrictions. Only randomized clinical trials comparing semaglutide to active comparators or placebo in adults were included. They used random-effects models for eye disorders and diabetic retinopathy, Peto OR with fixed effects for the rare NAION outcome, assessed bias with RoB 2.0, graded evidence quality with GRADE, and performed trial sequential analysis to evaluate data sufficiency.","limitations":"The NAION finding, while statistically significant, has a very wide confidence interval (1.02–15.02) suggesting imprecision. Trial sequential analysis confirmed the data were insufficient for definitive NAION conclusions. The meta-analysis relied on adverse event reporting from trials not specifically designed to detect ocular outcomes, which may lead to underreporting. Individual trial definitions of ocular adverse events may have varied."},{"rthcId":"RPEP-12737","title":"Clinical Outcomes and Complications of Basal, Bolus, and Combination Insulin Regimens in Type 2 Diabetes Mellitus: Evidence from Published Case Reports.","authors":"Natsir, Ramdhani M; Halimah, Eli; Diantini, Ajeng; Levita, Jutti","year":2025,"journal":"Diabetes, metabolic syndrome and obesity : targets and therapy, 18, 3215-3236","doi":"10.2147/DMSO.S545571","pmid":"40927666","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12738","title":"GLP-1 Receptor Agonists and SGLT2 Inhibitors in Stable Kidney Transplantation: Clinical Outcomes from a Cohort of Patients with Post-Transplant Diabetes Mellitus.","authors":"Navarrete, Ricardo E T; Freitas, Joana; Fonseca, Isabel; Cunha, Ana; Sa, Joao Roberto; Martins, La Salete","year":2025,"journal":"Journal of clinical medicine, 15(1)","doi":"10.3390/jcm15010181","pmid":"41517430","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12739","title":"Analysis of serum biomarkers associated with pain in Spanish greyhounds undergoing ovariohysterectomy.","authors":"Navarrete-Calvo, Rocio; Fernández-Sarmiento, Jose Andrés; Morgaz, Juan; Galán-Rodríguez, Alba; Gómez-Villamandos, Rafael J; Parra, Pablo; Del Mar Granados, María; Quirós-Carmona, Setefilla; Rodríguez-Gómez, Irene M","year":2025,"journal":"The Veterinary record","doi":"10.1002/vetr.6023","pmid":"41342433","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12740","title":"Elective semaglutide prescription enabled waitlisting and transplantation of otherwise ineligible obese renal transplant candidates.","authors":"Navaux, Emilie; La, Caroline; Dufour, Sylvain; Huberty, Vincent; Mourabit, Youssef; Caes, Thomas; Koliakos, Nikolaos; Mikhalski, Dimitri; Le Moine, Alain; Catalano, Concetta","year":2025,"journal":"Frontiers in transplantation, 4, 1623096","doi":"10.3389/frtra.2025.1623096","pmid":"41234778","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Of 23 obese kidney transplant candidates initially rejected due to obesity, semaglutide treatment (up to 1 mg/week subcutaneously) over a median of 12.2 months produced significant improvements: mean weight decreased by 11.4 kg (p ≤ 0.001), BMI dropped by 3.9 points (p ≤ 0.001), and waist circumference decreased by 9.6 cm (p ≤ 0.001).\n\n56.5% of patients (13 of 23) who had been rejected for transplantation were subsequently listed within a median of 5.4 months. Of those listed, 61.5% (8 patients) were successfully transplanted. No major side effects were reported during the treatment period. Starting weight, BMI, and waist circumference averaged 102.9 kg, 35.6, and 119.5 cm respectively.","whyItMatters":"Kidney failure patients with severe obesity face a cruel Catch-22: they need a transplant to improve their health, but their weight disqualifies them from surgery. This study shows that semaglutide can bridge that gap safely, opening the door to transplantation for patients who would otherwise remain on dialysis indefinitely. This could change pre-transplant protocols for obese patients at transplant centers worldwide.","specificNumbers":"","methodology":"This was a retrospective cohort study of patients rejected from kidney transplantation due to obesity between January 2021 and October 2023 at a single transplant center. All patients received subcutaneous semaglutide titrated up to 1 mg/week as part of their pre-transplant weight management. Researchers tracked body weight, BMI, and waist circumference over time, and monitored transplant waitlisting and transplantation outcomes.","limitations":"This was a small, single-center retrospective study with no control group. The 23-patient cohort limits statistical power and generalizability. There was no comparison to bariatric surgery or other weight loss interventions. Long-term post-transplant outcomes for semaglutide-treated patients were not reported. The study did not address potential interactions between semaglutide and immunosuppressive medications after transplant."},{"rthcId":"RPEP-12741","title":"GLP-1 medication and weight loss: Barriers and motivators among 1659 participants managed in a virtual setting.","authors":"Naveed, Maneeha; Perez, Cecilie; Ahmad, Ehtasham; Russell, Laura; Lees, Zoe; Maybury, Catriona","year":2025,"journal":"Diabetes, obesity & metabolism, 27(7), 3780-3788","doi":"10.1111/dom.16405","pmid":"40259493","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12742","title":"Sex differences in effectiveness of CGRP receptor antagonism for treatment of acute and persistent headache-like pain in a mouse model of mild traumatic brain injury.","authors":"Navratilova, Edita; Kopruszinski, Caroline M; Oyarzo, Janice; Barber, Kara R; Anderson, Trent; Dodick, David W; Schwedt, Todd J; Porreca, Frank","year":2025,"journal":"Cephalalgia : an international journal of headache, 45(2), 3331024251321087","doi":"10.1177/03331024251321087","pmid":"39980371","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12743","title":"Luteinizing Hormone-Releasing Hormone (LHRH)-Targeted Treatment in Ovarian Cancer.","authors":"Nayak, Pallavi; Varani, Michela; Giorgio, Anna; Campagna, Giuseppe; Caserta, Donatella; Signore, Alberto","year":2025,"journal":"International journal of molecular sciences, 26(24)","doi":"10.3390/ijms262411884","pmid":"41465311","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12744","title":"PHLA-SiNet: A novel peptide-HLA binding prediction model using heterogeneous Siamese neural networks.","authors":"Nazarloo, Maryam; Saadat, Mahsa; Zare-Mirakabad, Fatemeh","year":2025,"journal":"Computers in biology and medicine, 197(Pt A), 111017","doi":"10.1016/j.compbiomed.2025.111017","pmid":"40896909","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12745","title":"Advancements in Biomarkers for Early Detection and Risk Stratification of Cardiovascular Diseases-A Literature Review.","authors":"Nazir, Abubakar; Nazir, Awais; Afzaal, Usama; Aman, Shafaq; Sadiq, Safi Ur Rehman; Akah, Ozoemena Z; Jamal, Muhammad Shah Wali; Hassan, Syed Zawahir","year":2025,"journal":"Health science reports, 8(5), e70878","doi":"10.1002/hsr2.70878","pmid":"40432692","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12746","title":"From Prescription to Predicament: A Case of Semaglutide-Induced Discoid Lupus Erythematosus in an Adult Male Patient.","authors":"Nazzicone, Kristina; Sidiropoulos, Michael; O'Toole, Ashley","year":2025,"journal":"Cureus, 17(4), e81663","doi":"10.7759/cureus.81663","pmid":"40330408","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12747","title":"A potential association between tirzepatide and hypercalcemia in the setting of chronic hydrochlorothiazide use.","authors":"Nduma, Basil; Malapati, Sai Nikhitha; Vibhuti, Veeranna","year":2025,"journal":"Endocrinology, diabetes & metabolism case reports, 2025(3)","doi":"10.1530/EDM-25-0067","pmid":"40911613","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12748","title":"Shared mechanistic pathways of glucagon signalling: Unlocking its potential for treating obesity, metabolic dysfunction-associated steatotic liver disease, and other cardio-kidney-metabolic conditions.","authors":"Neff, Guy W","year":2025,"journal":"Diabetes, obesity & metabolism, 27(12), 6869-6883","doi":"10.1111/dom.70148","pmid":"41025406","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12749","title":"Glucagon-like peptide-1 agonists alleviate adenine-induced nephrotoxicity in rats: interaction with the renin-angiotensin system and role of NLRP-3 inflammasome, nephrin and KIM-1.","authors":"Nematalla, Hisham A; Elharoun, Mona; Sheta, Eman; Saleh, Samar R; Basta, Marianne; Eid, Ali H; El-Yazbi, Ahmed F","year":2025,"journal":"Biochemical pharmacology, 242(Pt 4), 117431","doi":"10.1016/j.bcp.2025.117431","pmid":"41110489","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12750","title":"Combined effect of continuous glucose monitoring and semaglutide: analysis of administrative claims.","authors":"Nemlekar, Poorva M; Hannah, Katia L; Green, Courtney R; Grace, Thomas; Lynch, Peter M; Castle, Jessica R; Norman, Gregory J","year":2025,"journal":"The American journal of managed care, 31(4), 183-188","doi":"10.37765/ajmc.2025.89719","pmid":"40227398","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 21,247 adults with type 2 diabetes using semaglutide, the 2,759 who also used CGM achieved significantly greater HbA1c improvements than the 18,488 using semaglutide alone (difference-in-differences: -0.55%, 95% CI: -0.64% to -0.47%, p < 0.0001).\n\nAmong CGM users, the proportion meeting the ADA target of HbA1c < 7.0% nearly doubled, and the proportion achieving the HEDIS target of HbA1c < 8.0% increased by more than 50%. These results suggest that CGM provides an additive benefit beyond the pharmacological effect of semaglutide alone.","whyItMatters":"This study provides real-world evidence that combining technology (CGM) with pharmacotherapy (semaglutide) produces better diabetes outcomes than medication alone. As both CGM and GLP-1 agonists become more widely prescribed, understanding their synergistic benefits can help clinicians optimize treatment and support expanded insurance coverage for CGM in type 2 diabetes patients.","specificNumbers":"","methodology":"Retrospective analysis of US healthcare administrative claims from the Optum Clinformatics database. Adults with type 2 diabetes using semaglutide between January 2019 and September 2022 were identified. The CGM cohort had at least one CGM-related claim; the control group used semaglutide without CGM. At least one baseline and one follow-up HbA1c lab value were required. Difference-in-differences analysis compared HbA1c changes between groups.","limitations":"This is a retrospective observational study using claims data, so it cannot prove causation. CGM users may be more health-engaged or have different baseline characteristics than non-users, introducing selection bias. The study could not control for differences in diet, exercise, or medication adherence between groups. Claims data may not capture all CGM use (e.g., over-the-counter devices). Semaglutide dose and formulation (oral vs. injectable) were not differentiated."},{"rthcId":"RPEP-12751","title":"Exploring Combined Use of Continuous Glucose Monitoring and Anti-Diabetes Medications on Glycaemic Control for People With Type 2 Diabetes Not Using Insulin.","authors":"Nemlekar, Poorva M; Hannah, Katia L; Green, Courtney R; Norman, Gregory J","year":2025,"journal":"Endocrinology, diabetes & metabolism, 8(5), e70089","doi":"10.1002/edm2.70089","pmid":"40851538","tags":[],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"Among over 52,000 adults with type 2 diabetes not using insulin, adding continuous glucose monitoring (CGM) was associated with a 0.45% greater HbA1c reduction compared to not using CGM (p<0.0001). The benefit of CGM was particularly pronounced when combined with GLP-1 receptor agonists, DPP-4 inhibitors, and sulfonylureas — these medications showed statistically significant interaction effects, meaning CGM amplified their glucose-lowering benefits more than it did for metformin or SGLT2 inhibitors.","whyItMatters":"CGM has been primarily studied in people using insulin, but most type 2 diabetes patients don't use insulin. This large study shows that CGM provides meaningful additional blood sugar control when paired with oral and injectable non-insulin medications, particularly GLP-1 drugs — supporting broader insurance coverage and clinical adoption of CGM technology.","specificNumbers":"n=52,394 · 4,086 CGM users vs 48,308 non-users · -0.45% greater A1c change · p<0.0001 · Significant interactions for GLP-1 RAs, DPP-4i, sulfonylureas","methodology":"Retrospective observational analysis of the Optum Clinformatics Data Mart database (administrative claims + linked lab data) from July 2018 through June 2023. CGM-naïve adults with non-insulin-treated type 2 diabetes using at least one of five anti-diabetes medication classes were identified. 6-month baseline and follow-up periods. Linear regression models tested main and interaction effects of CGM use with each medication class.","limitations":"Observational design cannot prove causation — CGM users may be more engaged with their health, leading to confounding. The study uses administrative claims which may not capture all relevant clinical variables. It does not distinguish between different CGM devices or assess how patients used CGM data to modify behavior."},{"rthcId":"RPEP-12752","title":"Structure-based design of macrocyclic peptides to generate functional antibodies against G protein-coupled receptors.","authors":"Nepveu-Traversy, Marie-Edith; Hassanzadeh, Malihe; Bruneau-Cossette, Laurent; Besserer-Offroy, Élie; Brouillette, Rebecca; Morissette, Sandra; Traboulsi, Hassan; Kirby, Karyn; Murza, Alexandre; Longpré, Jean-Michel; Breton, Billy; Gendron, Fernand-Pierre; Gaudreau, Simon; Boudreault, Pierre-Luc; Sarret, Philippe","year":2025,"journal":"Nature communications, 16(1), 11215","doi":"10.1038/s41467-025-66030-1","pmid":"41387675","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12753","title":"Consumption of Unprocessed and Ultraprocessed Foods in Adolescents with Obesity: Associations with Neuroendocrine Mediators of Appetite Regulation and Binge Eating Symptoms.","authors":"Neres, Patrícia Sousa; Ganen, Aline de Piano; Campos, Raquel Munhoz da Silveira; Carvalho Ferreira, Joana Pereira de; Oyama, Lila Missae; Dâmaso, Ana Raimunda; Masquio, Deborah Cristina Landi","year":2025,"journal":"Nutrients, 17(23)","doi":"10.3390/nu17233711","pmid":"41374002","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Lower consumption of unprocessed foods was associated with significantly higher ghrelin concentrations (p=0.023), greater body fat percentage (p=0.047), and reduced lean mass percentage (p=0.047). Agouti-related peptide (AgRP) was a positive predictor of ultraprocessed food consumption (β=0.30, p=0.04), independent of age, body fat, and binge eating symptoms. Six appetite-regulating peptides were measured: ghrelin, leptin, neuropeptide Y, AgRP, melanin-concentrating hormone, and α-MSH.","whyItMatters":"This study connects the dots between what obese teenagers eat, how their appetite hormones respond, and whether binge eating plays a role. Finding that AgRP independently predicts ultraprocessed food intake suggests a biological drive — not just behavioral preference — behind poor dietary choices in obesity, which could inform both nutritional counseling and potential peptide-targeted interventions.","specificNumbers":"","methodology":"Cross-sectional study of 96 adolescents with obesity recruited in São Paulo, Brazil (2010–2012). Researchers measured anthropometric data and body composition, assessed binge eating with the Binge Eating Scale, and evaluated dietary intake using a validated Food Frequency Questionnaire classified by the Nova food processing system. Blood levels of six neuroendocrine appetite mediators (ghrelin, leptin, NPY, AgRP, MCH, α-MSH) were analyzed.","limitations":"The cross-sectional design means causation cannot be established — it's unclear whether altered peptide levels drive food choices or result from them. The sample of 96 adolescents from a single city limits generalizability. Data were collected in 2010–2012, and dietary patterns may have shifted since then. Self-reported food intake is subject to recall bias, and the study did not account for socioeconomic factors that influence food access."},{"rthcId":"RPEP-12754","title":"Improvement in Helicobacter pylori Eradication Among Adults Receiving Semaglutide: A Population-Based Propensity-Score-Adjusted Analysis.","authors":"Ness, Asaf; Levi, Zohar; Belfer, Rachel Gingold; Dickman, Ram; Boltin, Doron","year":2025,"journal":"Helicobacter, 30(1), e70014","doi":"10.1111/hel.70014","pmid":"39902748","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12755","title":"Neo-antigen tumor vaccination depends on CD4-licensing conveyed by adeno-associated virus like particles.","authors":"Neukirch, Lasse; Uhrig-Schmidt, Silke; von Werthern, Katharina; Tuch, Alexandra; Kraske, Joscha A; Lyu, Yanhong; Lenoir, Benedicte; Eichmüller, Stefan B; Meyer, Marten; Zörnig, Inka; Jäger, Dirk; Schmidt, Patrick","year":2025,"journal":"Molecular therapy : the journal of the American Society of Gene Therapy, 33(10), 5003-5016","doi":"10.1016/j.ymthe.2025.07.014","pmid":"40671675","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12756","title":"Structural basis of inhibition of human NaV1.8 by the tarantula venom peptide Protoxin-I.","authors":"Neumann, Bryan; McCarthy, Stephen; Gonen, Shane","year":2025,"journal":"Nature communications, 16(1), 1459","doi":"10.1038/s41467-024-55764-z","pmid":"39920100","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12757","title":"Tirzepatide increased force of contraction in the isolated human atrium.","authors":"Neumann, Joachim; Hofmann, Britt; Kirchhefer, Uwe; Gergs, Ulrich","year":2025,"journal":"Naunyn-Schmiedeberg's archives of pharmacology, 398(10), 14451-14459","doi":"10.1007/s00210-025-04214-8","pmid":"40299022","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12758","title":"Ubrogepant, erenumab, and eptinezumab antagonize positive inotropic effects of the calcitonin gene-related peptide in the isolated human atrium.","authors":"Neumann, Joachim; Hofmann, Britt; Gergs, Ulrich","year":2025,"journal":"Naunyn-Schmiedeberg's archives of pharmacology, 398(9), 11909-11918","doi":"10.1007/s00210-025-04029-7","pmid":"40085216","tags":["neuropeptides","cardiovascular"],"studyType":"ex-vivo","evidenceStrength":"preliminary","keyFinding":"Three anti-migraine drugs that target the CGRP pathway — ubrogepant, erenumab, and eptinezumab — also reduce the force of heart contraction in isolated human atrial tissue at therapeutic concentrations. CGRP (calcitonin gene-related peptide), a key migraine peptide, also increases heart contraction force in human atrial tissue at nanomolar concentrations. All three anti-migraine drugs blocked this cardiac effect of CGRP, both when applied before and after CGRP.\n\nThe finding raises an important safety question: since CGRP plays a role in heart function, do anti-migraine drugs that block CGRP also affect the heart in living patients?","whyItMatters":"Millions of people take CGRP-targeting migraine drugs (like Aimovig/erenumab, Vyepti/eptinezumab, and Ubrelvy/ubrogepant). CGRP is present not just in the brain but in the heart, where it affects contraction force. This study is the first to show that therapeutic concentrations of these migraine drugs block CGRP's cardiac effects in human atrial tissue — raising questions about potential cardiovascular consequences of long-term CGRP inhibition.","specificNumbers":"CGRP: 1-100 nM range · Ubrogepant: 1 nM · Erenumab: 2 nM · Eptinezumab: 6 nM · All reduced force of contraction · Human atrial preparations from open-heart surgery patients","methodology":"Ex vivo study using isolated, electrically driven human atrial tissue preparations obtained from adult patients during open-heart surgery. CGRP was applied at increasing concentrations (1-100 nM) to measure its effect on force of contraction. Three anti-migraine drugs were then tested for their ability to block CGRP's cardiac effects, both as pre-treatment and as post-treatment. The PDE III inhibitor cilostamide was used to enhance CGRP's effects in some experiments.","limitations":"Isolated atrial tissue in a dish does not replicate the full complexity of a beating heart in a living person — compensatory mechanisms, autonomic nervous system regulation, and drug metabolism are absent. The tissue came from cardiac surgery patients who may not represent the typical migraine patient population. Whether reduced atrial contraction force at these concentrations has any clinical significance in living patients remains unknown."},{"rthcId":"RPEP-12759","title":"Cell-Permeable Peptide Inhibitors of the p53-hDM2 Interaction via Foldamer Helix Mimicry and Bis-Thioether Stapling.","authors":"Neuville, Maxime; Bourgeais, Mathieu; Li, Bo; Varajao, Laetitia; Hallé, François; Goudreau, Sébastien R; Thinon, Emmanuelle; Pasco, Morgane; Khatib, Abdel-Majid; Guichard, Gilles","year":2025,"journal":"Journal of medicinal chemistry, 68(1), 236-246","doi":"10.1021/acs.jmedchem.4c01762","pmid":"39719869","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12760","title":"Circadian-Tuned Peptide Drug/Gene Co-Delivery Nanocomplexes to Enhance Glioblastoma Targeting and Transfection.","authors":"Neves, Ana R; Vivès, Eric; Boisguérin, Prisca; Quintela, Telma; Costa, Diana","year":2025,"journal":"International journal of molecular sciences, 26(13)","doi":"10.3390/ijms26136130","pmid":"40649908","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The WRAP5 cell-penetrating peptide functionalized with a transferrin receptor ligand (Tf) successfully co-delivered temozolomide and a p53-encoding plasmid to U87 glioma cells. Computational modeling of circadian gene expression revealed key timing windows: the transferrin receptor expression peaked at T7 and T8 time points, while clock genes Bmal1 and Per2 peaked at T16 and T8, respectively.\n\nConfocal microscopy confirmed that intracellular uptake of the peptide nanocomplexes and p53 mRNA expression were highest at T8 — the time point coinciding with peak transferrin receptor and Per2 expression. Protein-level analysis confirmed these transcriptional changes, with T16 emerging as a favorable time point for maximizing therapeutic efficacy. The results demonstrate that synchronizing peptide nanocomplex delivery with tumor circadian biology can enhance both cellular uptake and therapeutic gene expression.","whyItMatters":"Glioblastoma has a median survival of about 15 months even with treatment, and temozolomide resistance is common. This study tackles two major challenges simultaneously: improving drug delivery using a peptide-based targeting system, and optimizing treatment timing using chronobiology. If tumors are most vulnerable to treatment at specific times in their biological clock cycle, timing drug administration accordingly could dramatically improve outcomes without increasing doses or side effects.","specificNumbers":"","methodology":"Researchers used a previously developed WRAP5 cell-penetrating peptide conjugated to a transferrin receptor ligand for targeted delivery of temozolomide and p53 plasmid DNA to U87 glioma cells. Circadian oscillations of clock genes (Bmal1, Per2) and the transferrin receptor were mapped using two computational models. Confocal microscopy assessed intracellular uptake at different circadian time points. mRNA and protein analysis measured p53 expression levels across the circadian cycle to identify optimal treatment windows.","limitations":"This is entirely an in vitro study using U87 glioma cells — one of the most commonly used but least representative glioblastoma cell lines. The circadian oscillations in cultured cells may not reflect those in actual brain tumors, which are influenced by the patient's sleep-wake cycle, brain microenvironment, and blood-brain barrier. No in vivo or animal model data is presented. The blood-brain barrier, the major obstacle for glioblastoma drug delivery, was not addressed in this cell culture system."},{"rthcId":"RPEP-12761","title":"Cardiovascular outcomes with exenatide in type 2 diabetes according to ejection fraction: The EXSCEL trial.","authors":"Neves, João Sérgio; Leite, Ana Rita; Mentz, Robert J; Holman, Rury R; Zannad, Faiez; Butler, Javed; Packer, Milton; Ferreira, João Pedro","year":2025,"journal":"European journal of heart failure, 27(3), 540-551","doi":"10.1002/ejhf.3478","pmid":"39381950","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12762","title":"Efficacy of tirzepatide versus semaglutide in achieving therapeutic targets in type 2 diabetes: a post hoc analysis of the SURPASS-2 Trial.","authors":"Neves, João Sérgio; Leite, Ana Rita; Vale, Catarina; Marques, Pedro; Vasques-Nóvoa, Francisco; Leite-Moreira, Adelino; Ferreira, João Pedro","year":2025,"journal":"Diabetologia","doi":"10.1007/s00125-025-06637-7","pmid":"41419618","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"All three doses of tirzepatide (5, 10, and 15 mg) outperformed semaglutide 1 mg in helping patients achieve multiple standard and intensive therapeutic targets simultaneously at 40 weeks.\n\nFor standard targets, 57% of patients on tirzepatide 15 mg met three or more goals versus 34% on semaglutide. For intensive targets, the gap was even wider: 29% on tirzepatide 15 mg versus 8% on semaglutide achieved three or more goals.\n\nTirzepatide significantly increased the odds of achieving both standard and intensive weight loss targets (>10% weight loss: OR 2.72; >15% weight loss: OR 3.86) and intensive blood pressure targets (OR 1.45). Tirzepatide also improved HbA1c target attainment across both standard and intensive thresholds.","whyItMatters":"Most diabetes management focuses on individual targets like blood sugar. But patients who simultaneously control HbA1c, weight, blood pressure, and cholesterol have far better long-term outcomes. This analysis shows tirzepatide's dual GLP-1/GIP mechanism provides a meaningful advantage over semaglutide across multiple metabolic dimensions — not just one — which could translate to better prevention of diabetes complications.","specificNumbers":"","methodology":"This was a post hoc analysis of the SURPASS-2 trial, a randomized phase 3 study of 1,879 adults with type 2 diabetes. Participants had been randomized to tirzepatide (5, 10, or 15 mg weekly) or semaglutide (1 mg weekly). Researchers compared the proportion of patients meeting standard and intensive therapeutic targets for HbA1c, weight loss, blood pressure, and lipid profile at 40 weeks. Data was accessed through the Vivli clinical research data platform.","limitations":"This is a post hoc analysis, not a pre-specified endpoint of the original trial, which limits the strength of causal conclusions. The comparison used semaglutide 1 mg, not the higher 2.4 mg dose approved for weight management. The 40-week timeframe may not capture long-term differences in cardiovascular outcomes or complications. The original SURPASS-2 trial population may not represent all type 2 diabetes patients."},{"rthcId":"RPEP-12763","title":"GLP-1 Receptor Agonists for the Prevention of New-Onset Heart Failure: A Systematic Review and Meta-Analysis of Placebo-Controlled Randomized Clinical Trials.","authors":"Neves, João Sérgio; Lobato, Carolina B; Leite, Ana Rita; Vale, Catarina; Vasques-Nóvoa, Francisco; Saraiva, Francisca; Leite-Moreira, Adelino; Holst, Jens J; Ferreira, João Pedro","year":2025,"journal":"Obesity reviews : an official journal of the International Association for the Study of Obesity, e70043","doi":"10.1111/obr.70043","pmid":"41287923","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12764","title":"Recommendations for the use of natriuretic peptides for early diagnosis of heart disease in patients with diabetes: A consensus report by SPEDM, SPC, NEDM-SPMI and APMGF.","authors":"Neves, João Sérgio; Baptista, Rui; Azevedo de Pape, Estêvão; Rodrigues Pereira, Manuel; Paulos, Rita; Pinheiro Dos Santos, Jonathan; Gavina, Cristina; Jácome de Castro, João","year":2025,"journal":"Revista portuguesa de cardiologia : orgao oficial da Sociedade Portuguesa de Cardiologia = Portuguese journal of cardiology : an official journal of the Portuguese Society of Cardiology, 44(1), 57-67","doi":"10.1016/j.repc.2024.07.010","pmid":"39547648","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12765","title":"Therapeutic horizons in metabolic dysfunction-associated steatohepatitis.","authors":"Newsome, Philip N; Loomba, Rohit","year":2025,"journal":"The Journal of clinical investigation, 135(13)","doi":"10.1172/JCI186425","pmid":"40590228","tags":["glp-1-agonists","incretin-therapies"],"studyType":"Review","evidenceStrength":"high","keyFinding":"Multiple peptide-based therapies are showing substantial promise for treating MASH (metabolic dysfunction-associated steatohepatitis), the progressive form of fatty liver disease. GLP-1 agonists (semaglutide), dual agonists (tirzepatide, survodutide), and triple agonists are among the most advanced candidates. Recent trials demonstrate these drugs can resolve liver inflammation and improve fibrosis — the two key histological endpoints.\n\nOther promising approaches include PPAR agonists (lanifibranor), FGF21 analogs (pegozafermin), THR-β agonists (resmetirom, the first FDA-approved MASH drug), and fatty acid synthase inhibitors. The field is moving toward combination therapies and precision medicine approaches using genetic variants like PNPLA3 to guide treatment selection.","whyItMatters":"MASH is now a leading cause of chronic liver disease globally, driven by the obesity and diabetes epidemics. Until recently there were no approved drugs for it. The emergence of incretin-based peptide therapies — many of them already approved for diabetes and obesity — represents a potential paradigm shift. These drugs could simultaneously treat patients' metabolic disease and their liver disease.","specificNumbers":"Review covering semaglutide, tirzepatide, survodutide, lanifibranor, pegozafermin, resmetirom · MASH is leading cause of chronic liver disease · driven by obesity + T2D","methodology":"Comprehensive narrative review published in the Journal of Clinical Investigation. The authors synthesize evidence from recent clinical trials of MASH therapeutics, regulatory developments, biomarker research, and emerging precision medicine approaches. The review covers drugs from Phase II through FDA approval.","limitations":"As a review, this presents no new data. The field is moving rapidly, so some information may become outdated quickly. The review focuses on pharmacological approaches and gives less attention to lifestyle interventions. Many of the promising agents discussed are still in clinical trials and may not succeed."},{"rthcId":"RPEP-12766","title":"Real-World Weight Loss Observed With Semaglutide and Tirzepatide in Patients with Overweight or Obesity and Without Type 2 Diabetes (SHAPE).","authors":"Ng, Carmen D; Divino, Victoria; Wang, Julia; Toliver, Joshua C; Buss, Marcio","year":2025,"journal":"Advances in therapy, 42(11), 5468-5480","doi":"10.1007/s12325-025-03340-2","pmid":"40875186","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12767","title":"Semaglutide use before single-level lumbar fusion associated with fewer readmissions and 90-day costs.","authors":"Ng, Mitchell K; Mastrokostas, Paul G; Rodriguez, Ariel N; Razi, Abigail; Mastrokostas, Leonidas E; Emara, Ahmed K; Ford, Brian T; Xu, Jacquelyn J; Dalton, Jonathan; Narayanan, Rajkishen; Kepler, Christopher K; Hilibrand, Alan S; Vaccaro, Alexander R; Monsef, Jad Bou; Razi, Afshin E","year":2025,"journal":"Journal of craniovertebral junction & spine, 16(4), 401-407","doi":"10.4103/jcvjs.jcvjs_156_25","pmid":"41377827","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 3,452 semaglutide users matched against 15,486 controls undergoing single-level lumbar fusion, semaglutide use was associated with significantly lower 90-day readmission rates (8.7% vs. 11.4%) and lower 90-day costs. No significant differences were found in rates of stroke, heart attack, blood clots, pneumonia, low blood sugar, or surgical site infections.\n\nThe study suggests semaglutide provides perioperative benefits for spine surgery patients with diabetes without increasing complication risk.","whyItMatters":"As semaglutide becomes one of the most prescribed medications worldwide, understanding its effects on surgical outcomes is crucial. This study provides reassuring evidence that patients on semaglutide can safely undergo lumbar spine surgery — and may actually experience better outcomes with fewer readmissions and lower costs. This is particularly important given the large number of diabetic patients who need spine surgery.","specificNumbers":"","methodology":"A retrospective cohort study using a national claims database (2010–2021). Semaglutide users (N=3,452) were propensity-matched 1:5 to controls (N=15,486) based on age, sex, BMI, smoking, diabetes complications, medication use, and comorbidity index. Outcomes were analyzed using multivariate logistic regression with Bonferroni correction (significance at P<0.003).","limitations":"Retrospective design cannot prove causation. Claims database data lacks clinical detail on semaglutide dosing, duration, and timing relative to surgery. The Bonferroni correction makes significance thresholds conservative. Database limitations may lead to coding inaccuracies. The study period (2010–2021) captures early semaglutide use patterns that may not reflect current prescribing."},{"rthcId":"RPEP-12768","title":"Semaglutide use is associated with higher rates of pseudarthrosis and dysphagia in patients undergoing posterior cervical fusion.","authors":"Ng, Mitchell K; Mastrokostas, Paul G; Mastrokostas, Leonidas E; Tabbaa, Ameer; Johnson, Matthew; Monsef, Jad Bou; Razi, Afshin E","year":2025,"journal":"The spine journal : official journal of the North American Spine Society, 25(9), 1974-1980","doi":"10.1016/j.spinee.2025.03.023","pmid":"40154624","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12769","title":"Mitochondrial heteroplasmy-phenotype correlation and response to glucose lowering therapy in subjects with m.3243A>G mutations.","authors":"Ng, N; Sanchez-Lechuga, B; McCarrick, C J; Mangan, C; Burke, M; Ioana, J A; Gavin, C; O'Byrne, R; O'Byrne, J J; Byrne, M M","year":2025,"journal":"Diabetes & metabolism, 51(5), 101678","doi":"10.1016/j.diabet.2025.101678","pmid":"40541739","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12770","title":"GLP-1 receptor agonists and inflammatory pathway modulation: Dual targeting of metabolic and immune dysfunction in insulin resistance.","authors":"Ngabea, Murtala A; Dimeji, Igbayilola Yusuff","year":2025,"journal":"Biochemical and biophysical research communications, 789, 152822","doi":"10.1016/j.bbrc.2025.152822","pmid":"41161090","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12771","title":"Antimicrobial peptides: natural templates for next-generation therapeutics against antimicrobial resistance.","authors":"Ngashangva, Ng; Huidrom, Surmani; Devi, Indira Sarangthem","year":2025,"journal":"Frontiers in cellular and infection microbiology, 15, 1720027","doi":"10.3389/fcimb.2025.1720027","pmid":"41561088","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12772","title":"Application of Antimicrobial Peptides (AMPs) in Treatment of Osteomyelitis in Human and Veterinary Orthopedics.","authors":"Nguyen Ngoc, Dominika; Latalski, Michał; Danielewicz, Anna; Szponder, Tomasz; Wessely-Szponder, Joanna; Mazur, Ewa","year":2025,"journal":"Journal of functional biomaterials, 16(3)","doi":"10.3390/jfb16030090","pmid":"40137369","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12773","title":"Neoantigen-based mRNA vaccine exhibits superior anti-tumor activity compared to synthetic long peptides in an in vivo lung carcinoma model.","authors":"Nguyen, Cao Minh; Vu, Trung T; Nguyen, Minh Nguyen; Tran-Nguyen, Thao-Suong; Huynh, Chi Thien; Ha, Quang Thanh; Nguyen, Hoai-Nghia; Tran, Le Son","year":2025,"journal":"Cancer immunology, immunotherapy : CII, 74(4), 145","doi":"10.1007/s00262-025-03992-7","pmid":"40072566","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12774","title":"Diversity-oriented synthesis of second generation guanidinium-rich transporters toward cell-selective penetration.","authors":"Nguyen, Duc Tai; Desgagné, Michael; Laniel, Andréanne; Lavoie, Christine; Boudreault, Pierre-Luc","year":2025,"journal":"Bioorganic chemistry, 154, 108041","doi":"10.1016/j.bioorg.2024.108041","pmid":"39672076","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12775","title":"Modular helix stabilization via alkenyl butylcarbamate staples: effects of staple length, stereochemistry, and directionality.","authors":"Nguyen, Ha T N; Pham, Thanh K; Kim, Young-Woo","year":2025,"journal":"Bioorganic & medicinal chemistry, 129, 118334","doi":"10.1016/j.bmc.2025.118334","pmid":"40729819","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12776","title":"Engineered Tandem Thymosin Peptide Promotes Corneal Wound Healing.","authors":"Nguyen, Joseph; Verma, Sudhir; Vuong, Vivian T; Queener, Hope; Coulson-Thomas, Vivien Jane; Gesteira, Tarsis Ferreira","year":2025,"journal":"Investigative ophthalmology & visual science, 66(14), 31","doi":"10.1167/iovs.66.14.31","pmid":"41235866","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12777","title":"Porcine placenta peptides as a complementary functional food for skin rejuvenation: A 12-week randomized, double-blind, placebo-controlled trial.","authors":"Nguyen, Ngoc Ha; Lee, Young In; Chau, Nam Hao; Lee, Sung Jun; Kim, Inah; Kim, Jinhak; Baek, Kwang-Soo; Lee, Ju Hee","year":2025,"journal":"Complementary therapies in medicine, 95, 103271","doi":"10.1016/j.ctim.2025.103271","pmid":"41138781","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12778","title":"Safety, efficacy, and compliance of moderate-to-high dose eptinezumab and erenumab in chronic migraine patients with medication-overuse headache: an updated systematic review and meta-analysis.","authors":"Nguyen, Nhan; Ho Quang Tri, Vinh; Nguyen Ngoc Dan, Vy; Bao Tran, Nghi; Olah, Laszlo; Heja, Mate","year":2025,"journal":"The journal of headache and pain, 26(1), 99","doi":"10.1186/s10194-025-02047-7","pmid":"40329188","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12779","title":"Peptide YY in Type 2 Diabetes: A Complementary Gut Hormone with Therapeutic Potential Beyond GLP-1.","authors":"Nguyen, Nhi Thi; Park, Jae-Hyung","year":2025,"journal":"Nutrients, 17(21)","doi":"10.3390/nu17213468","pmid":"41228539","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12780","title":"Clinical Data Mega-Collection of Obesity and Obesity-Related Trials: Primary Inclusion Criteria from All Studies and Highlights of Clinical Efficacy Analysis of GLP-1 Drugs.","authors":"Nguyen, Trung Tin; Elmaleh, David R","year":2025,"journal":"Journal of clinical medicine, 14(3)","doi":"10.3390/jcm14030812","pmid":"39941484","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Both semaglutide and tirzepatide perform comparably at the FDA's 5% body weight loss threshold. However, tirzepatide significantly outperforms semaglutide as the weight loss target increases from 5% to 20%, with fewer participants failing to reach higher thresholds.\n\nTirzepatide showed particularly strong effects in people with type 2 diabetes compared to semaglutide. The analysis also revealed significant disparities in trial participation by race and geographic region across all 10,407 studies reviewed. Critically, the researchers found that the specific effects of weight loss therapies on the kidneys, heart, different muscle types, bones, and regional fat distribution were rarely investigated or reported during clinical trial periods or longer-term monitoring.","whyItMatters":"With the GLP-1 drug market exploding, this large-scale analysis provides an important reality check. While tirzepatide appears to be the more potent drug for weight loss, the authors emphasize that chasing maximum weight loss numbers may not serve patients best. The finding that organ-specific effects (heart, kidney, muscle, bone) are largely unstudied during trials raises serious questions about what we don't know about these drugs, even as millions of people take them.","specificNumbers":"","methodology":"The researchers used an AI-powered software tool called TAITAN to perform a mega-collection and analysis of clinical data from 10,407 obesity and obesity-related disease trials and their associated PubMed publications through the end of 2024. They analyzed inclusion criteria patterns (particularly BMI thresholds), trial growth trends, demographic representation, and then focused specifically on comparing clinical efficacy data for semaglutide and tirzepatide at different weight loss benchmarks.","limitations":"The analysis relied on AI software (TAITAN alpha version) for data collection and processing, and the accuracy of automated data extraction isn't independently validated in this paper. The comparison between semaglutide and tirzepatide is indirect — drawn from separate trials rather than head-to-head studies. The mega-collection approach may include studies of varying quality. The focus on primary endpoints may miss important secondary outcomes. The software tool's methodology isn't fully transparent."},{"rthcId":"RPEP-12781","title":"Cardiovascular Outcomes with Tirzepatide versus Dulaglutide in Type 2 Diabetes.","authors":"Nicholls, Stephen J; Pavo, Imre; Bhatt, Deepak L; Buse, John B; Del Prato, Stefano; Kahn, Steven E; Lincoff, A Michael; McGuire, Darren K; Miller, Debra; Nauck, Michael A; Nishiyama, Hiroshi; Nissen, Steven E; Sattar, Naveed; Weerakkody, Govinda; Wiese, Russell J; Zinman, Bernard; Zoungas, Sophia; Basile, Jan; Davies, Melanie J; Giorgino, Francesco; Kellerer, Monika; Ji, Linong; Varkonyi, Tamas; Menon, Venu; Broder, Jonathan C; Herschtal, Alan; D'Alessio, David","year":2025,"journal":"The New England journal of medicine, 393(24), 2409-2420","doi":"10.1056/NEJMoa2505928","pmid":"41406444","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12782","title":"Review: An Update on CGRP Monoclonal Antibodies for the Preventive Treatment of Episodic Migraine.","authors":"Nicol, Kelly S; Burkett, John G","year":2025,"journal":"Current pain and headache reports, 29(1), 55","doi":"10.1007/s11916-025-01365-4","pmid":"39998706","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Long-term studies published in 2023-2024 confirm ongoing safety and efficacy for all four CGRP-targeting monoclonal antibodies in episodic migraine prevention. These therapies reduce monthly migraine days and increase quality of life while being better tolerated than non-specific migraine preventive therapies (such as beta-blockers, antidepressants, and anticonvulsants).\n\nThe accumulated evidence has led to the 2024 American Headache Society (AHS) consensus statement recommending CGRP monoclonal antibodies be considered as first-line preventive treatment in episodic migraine — a significant elevation in their clinical positioning.","whyItMatters":"For decades, migraine prevention relied on drugs originally developed for other conditions (blood pressure medications, antidepressants, anti-seizure drugs) that often had significant side effects and limited efficacy. CGRP-targeting therapies represent the first migraine-specific preventive treatments, designed to directly block the neuropeptide pathway driving migraine attacks. Their elevation to first-line status by the AHS marks a paradigm shift in headache medicine and validates the peptide-targeted therapeutic approach.","specificNumbers":"","methodology":"Narrative review of clinical evidence for the safety and efficacy of four CGRP-targeted monoclonal antibodies (erenumab, fremanezumab, galcanezumab, eptinezumab) in episodic migraine prevention, with a focus on recent studies published in 2023-2024.","limitations":"This is a narrative review, not a systematic review or meta-analysis. The abstract does not report specific efficacy numbers (e.g., reduction in monthly migraine days) for each antibody. Long-term data typically extend to 1-3 years, and very long-term effects (5+ years) are still accumulating. Cost and access barriers remain significant, as these biologic therapies are expensive. Head-to-head comparisons between the four antibodies are limited."},{"rthcId":"RPEP-12783","title":"The Role of Exenatide, a Glucagon-Like Peptide-1 (GLP-1) Receptor Agonist, in Idiopathic Intracranial Hypertension and Polycystic Ovary Syndrome: A Case Report.","authors":"Nicolaou, Despina; Nicolaou, Nicolas; Douglas, Lisa M; Christou, Savvas","year":2025,"journal":"Cureus, 17(10), e93846","doi":"10.7759/cureus.93846","pmid":"41054431","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A 29-year-old woman with PCOS and IIH without papilledema (IIHWOP) was treated with exenatide after intolerance to acetazolamide. Key findings:\n\n- Headache frequency and diplopia (double vision) improved early, independent of weight loss, suggesting direct receptor-mediated reduction of cerebrospinal fluid secretion and intracranial pressure\n- Menstrual cycles and hormonal profile improved beyond the effects of metformin alone\n- Insulin resistance improved\n- The patient had gained 15 kg over eight months prior to treatment\n- IIH was diagnosed by MRI (enlarged pituitary fossa, partial empty sella, optic nerve sheath dilatation) and lumbar puncture showing raised opening pressure of 280 mmH₂O with normal CSF composition","whyItMatters":"IIH and PCOS frequently co-occur in young obese women but are typically treated with different medications. The discovery that GLP-1 receptors are present on choroid plexus cells (which produce cerebrospinal fluid) and ovarian tissue suggests that GLP-1 peptide drugs could treat both conditions simultaneously through direct receptor effects — not just through weight loss. This opens a new therapeutic application for GLP-1 agonists and could simplify treatment for patients with both conditions.","specificNumbers":"","methodology":"Single-patient case report documenting clinical course after initiating exenatide for a patient with both IIH and PCOS. Diagnosis was confirmed by ophthalmic examination, MRI, and lumbar puncture. Clinical outcomes tracked included headache frequency, visual symptoms, menstrual regularity, hormonal profile, and insulin resistance markers.","limitations":"This is a single case report (n=1), the weakest form of clinical evidence. Causation cannot be established — improvements could be coincidental or related to other factors. The early headache improvement attributed to direct receptor effects was inferred but not confirmed by repeat lumbar puncture or intracranial pressure monitoring. The degree to which improvements in PCOS symptoms exceeded metformin's effects alone is difficult to quantify in a single patient. Longer follow-up is needed to assess sustained benefit."},{"rthcId":"RPEP-12784","title":"Effectiveness of Low Doses of Semaglutide on Weight Loss and Body Composition Among Women in Their Menopause.","authors":"Nicolau, Joana; Blanco-Anesto, Jorge; Bonet, Aina; Félix-Jaume, Juan José; Gil-Palmer, Apolonia","year":2025,"journal":"Metabolic syndrome and related disorders, 23(1), 70-76","doi":"10.1089/met.2024.0124","pmid":"39761057","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12785","title":"Effects of six months treatment with liraglutide among patients with psoriasis and obesity, beyond metabolic control?","authors":"Nicolau, Joana; Nadal, Antoni; Sanchís, Pilar; Pujol, Antelm; Tamayo, María Isabel; Nadal, Cristina; Masmiquel, Lluís","year":2025,"journal":"Medicina clinica, 164(11), 106941","doi":"10.1016/j.medcli.2025.106941","pmid":"40267547","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12786","title":"The pharmacotherapeutic potential of neuropeptide Y for chronic pain.","authors":"Nie, Al A; Taylor, Bradley K","year":2025,"journal":"Journal of internal medicine, 298(4), 280-296","doi":"10.1111/joim.20118","pmid":"40754889","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12787","title":"The Predictive Value of the Neutrophil Percentage-to-Albumin Ratio for Early Recurrence of Atrial Fibrillation After Radiofrequency Catheter Ablation.","authors":"Nie, Lujing; Nie, Qingmei; Liu, Kesen; Zhang, Shujie; Wang, Yujie; Yu, Yaxuan; Feng, Wenjiu; Chen, Yanbo","year":2025,"journal":"Journal of inflammation research, 18, 15615-15626","doi":"10.2147/JIR.S557322","pmid":"41234505","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12788","title":"Glucagon-Like Peptide-1 Receptor Agonists for the Treatment of Suboptimal Initial Clinical Response and Weight Gain Recurrence After Bariatric Surgery: a Systematic Review and Meta-analysis.","authors":"Nie, Yuntao; Zhang, Yiran; Liu, Baoyin; Meng, Hua","year":2025,"journal":"Obesity surgery, 35(3), 808-822","doi":"10.1007/s11695-025-07733-8","pmid":"39948306","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 19 studies and 1,290 patients with suboptimal initial response or weight regain after bariatric surgery, GLP-1 receptor agonists produced the following results after at least 3 months:\n\n• Tirzepatide: 15.50% total weight loss (TWL), 12.60 kg\n• Semaglutide: 11.38% TWL, 11.62 kg\n• Liraglutide: 9.24% TWL, 8.56 kg\n\nLonger treatment duration improved outcomes: semaglutide at 12 months achieved 13.15% TWL and 14.68 kg loss, compared to 10.18% TWL and 9.43 kg at 6 months. Liraglutide showed similar time-dependent gains (10.80% TWL at ≥12 months vs 7.65% at ≤6 months).\n\nSignificant improvements were also seen in triglycerides, total cholesterol, LDL cholesterol, HbA1c, and ALT levels. Common adverse effects included nausea (23%), constipation (10%), fatigue (8%), vomiting (6%), diarrhea (6%), and headache (6%), with only 3% discontinuing due to side effects.","whyItMatters":"Weight regain affects a significant proportion of bariatric surgery patients and has been a persistent clinical challenge with limited treatment options. This meta-analysis provides strong pooled evidence that GLP-1 receptor agonists — already established for primary obesity treatment — are also effective as a rescue strategy after surgery, potentially filling an important therapeutic gap.","specificNumbers":"","methodology":"Systematic review and meta-analysis with literature search across online databases. Nineteen studies including 1,290 bariatric surgery patients with suboptimal initial clinical response or weight gain recurrence were included. Primary outcomes were percentage total weight loss and absolute weight loss. Secondary outcomes included changes in biochemical markers (lipids, HbA1c, liver enzymes) and adverse effect rates. Results were stratified by drug type (liraglutide, semaglutide, tirzepatide) and treatment duration.","limitations":"The 19 included studies were primarily observational and retrospective, lacking randomized controlled trial data. Heterogeneity across studies in surgical procedures, time since surgery, and treatment protocols may affect pooled estimates. Tirzepatide data were limited compared to liraglutide and semaglutide. Long-term outcomes beyond 12 months are poorly characterized. Publication bias cannot be excluded."},{"rthcId":"RPEP-12789","title":"Bulk Measurement of Membrane Permeability for Random Cyclic Peptides in Living Cells to Guide Drug Development.","authors":"Nielsen, Alexander L; Bartling, Christian R O; Zarda, Anne; De Sadeleer, Nathan; Neeser, Rebecca M; Schwaller, Phillippe; Strømgaard, Kristian; Heinis, Christian","year":2025,"journal":"Angewandte Chemie (International ed. in English), 64(27), e202500493","doi":"10.1002/anie.202500493","pmid":"40052878","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12790","title":"A Bioequivalence Study of Two Formulations of Oral Semaglutide in Healthy Participants.","authors":"Nielsen, Mette Søndergaard; Brøndsted, Lise; Kankam, Martin; Morelli, Gaetano; Nguyen, David; Skjøth, Trine Vang; Patted, Usha Rani; van Hout, Marloes","year":2025,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 16(2), 269-287","doi":"10.1007/s13300-024-01674-8","pmid":"39708086","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12791","title":"Cell-Derived Nanocarriers of Apoptotic Bodies with an Antimicrobial Peptide for Targeting Intracellular S. aureus Infections.","authors":"Nieto-Marín, Valentina; Fernandez-Soliz, Ian Alejandro; Arboleda Valencia, Jorge William; Pletzer, Daniel; Buccini, Danieli Fernanda; Franco, Octávio Luiz","year":2025,"journal":"ACS applied bio materials, 8(11), 9875-9892","doi":"10.1021/acsabm.5c01222","pmid":"41124675","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12792","title":"Comparative Efficacy of Endoscopic Sleeve Gastroplasty (Esg) Versus Liraglutide in Weight Loss and Remission Of Obesity-Related Comorbidities: Twelve Months Follow-Up Results.","authors":"Nigro, Stefania; Vinciguerra, Federica; Guccione, Fabio; Alibrandi, Angela; Filannino, Ruggiero; Navarra, Giuseppe","year":2025,"journal":"Obesity surgery, 35(9), 3531-3539","doi":"10.1007/s11695-025-08155-2","pmid":"40779281","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 43 randomized patients (23 ESG, 20 liraglutide) with class I-II obesity:\n\n• At 3 and 6 months: ESG significantly outperformed liraglutide for both %EWL and %TWL (P=0.001)\n• At 12 months: No statistically significant difference between groups — the ESG advantage had disappeared\n• ESG pattern: rapid initial weight loss followed by some weight regain after 6 months\n• Liraglutide pattern: slower but more consistent weight loss that continued beyond 6 months\n• Resolution of obesity-related comorbidities: no significant differences between groups at any time point (3, 6, or 12 months)\n• Safety: no major complications or significant side effects in either group","whyItMatters":"Patients with moderate obesity face a choice between procedures and medications, but until now there were no head-to-head trials comparing them. This study reveals a crucial insight: the procedure wins early but the drug wins late, and they converge at 12 months. This trajectory pattern — fast surgical loss with regain vs slow pharmacological loss with persistence — has major implications for patient counseling and treatment selection.","specificNumbers":"","methodology":"Prospective, randomized controlled, single-center study. 43 patients with class I and II obesity were randomized to ESG (n=23) or liraglutide (n=20). All participants received standardized follow-up with both surgeon and nutritionist assessments. Outcomes measured at 3, 6, and 12 months included %EWL, %TWL, and resolution of obesity-related comorbidities.","limitations":"Very small sample size (43 patients) limits statistical power and generalizability. Single-center study. Only liraglutide (the least potent currently available GLP-1 agonist) was tested — semaglutide or tirzepatide might perform differently. Only 12-month follow-up; longer data are needed. The ESG weight regain trend at 12 months needs longer follow-up to characterize. Class I-II obesity only; may not apply to severe obesity. The authors acknowledge larger studies with longer follow-up are needed."},{"rthcId":"RPEP-12793","title":"Postmarketing safety of migraine prophylactic monoclonal antibodies: An EudraVigilance database analysis of eptinezumab, fremanezumab, galcanezumab, and erenumab.","authors":"Nikitina, Victoria; Santi Laurini, Greta; Montanaro, Nicola; Motola, Domenico","year":2025,"journal":"Headache, 65(7), 1080-1094","doi":"10.1111/head.14962","pmid":"40439253","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12794","title":"Subocclusive ileus following off-label high-dose semaglutide use.","authors":"Nikolaeva, Arina; Vandeputte, Martin","year":2025,"journal":"Endocrinology, diabetes & metabolism case reports, 2025(4)","doi":"10.1530/EDM-25-0081","pmid":"41294925","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A 37-year-old woman with normal BMI developed subocclusive ileus (functional intestinal obstruction) following unsupervised, off-label use of semaglutide for cosmetic weight loss purposes.","whyItMatters":"As semaglutide becomes widely available through non-medical channels (online pharmacies, social media promotion), people without obesity or diabetes are increasingly using it for cosmetic weight loss without medical supervision. This case demonstrates that GLP-1 drugs carry real risks — including potentially life-threatening intestinal complications — even in young, otherwise healthy individuals. It underscores the importance of medical oversight when using these potent medications.","specificNumbers":"","methodology":"Single case report documenting the clinical presentation, diagnosis, and outcome of a patient who developed gastrointestinal complications from non-prescribed semaglutide use.","limitations":"Single case report — the lowest level of clinical evidence. Cannot establish the incidence of this complication or definitively prove the semaglutide caused the ileus. The specific dose, duration of use, and outcome details are minimal in the abstract. No information about whether the patient had other risk factors for ileus."},{"rthcId":"RPEP-12795","title":"NetMHCpan-4.2: improved prediction of CD8+ epitopes by use of transfer learning and structural features.","authors":"Nilsson, Jonas Birkelund; Greenbaum, Jason; Peters, Bjoern; Nielsen, Morten","year":2025,"journal":"Frontiers in immunology, 16, 1616113","doi":"10.3389/fimmu.2025.1616113","pmid":"40852704","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12796","title":"Pharmacological characterization of ubrogepant and atogepant in cAMP assays at human, rat, and mouse calcitonin family receptors in transfected cells.","authors":"Nimick, Mhairi; Alexander, Tyla I; Garelja, Michael L; Walker, Christopher S; Banerjee, Pradeep; Hay, Debbie L","year":2025,"journal":"Biochemical pharmacology, 242(Pt 1), 117295","doi":"10.1016/j.bcp.2025.117295","pmid":"40889535","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12797","title":"Recombinant Expression of a New Antimicrobial Peptide Composed of hBD-3 and hBD-4 in Escherichia coli and Investigation of Its Activity Against Multidrug-Resistant Bacteria.","authors":"Ning, Nianzhi; Yan, Han; Cao, Binwang; Yu, Wenjing; Zhang, Liangyan; Li, Deyu; Li, Tao; Zhang, Xingxiao; Wang, Hui","year":2025,"journal":"Probiotics and antimicrobial proteins, 17(6), 5066-5074","doi":"10.1007/s12602-025-10456-y","pmid":"39825027","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12798","title":"Intranasal vasopressin, but not oxytocin, decreases ethanol intake in socially housed mice.","authors":"Nipper, Michelle A; Zweig, Jonathan A; Johnson, Michael C; Abshire, Kelly M; Ryabinin, Andrey E","year":2025,"journal":"Psychopharmacology","doi":"10.1007/s00213-025-06962-0","pmid":"41207899","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12799","title":"Psychiatric and psychological adverse effects associated with dulaglutide, semaglutide, and liraglutide: A vigibase study.","authors":"Nishida, Kazuki; Chrétien, Basile; Dolladille, Charles; Ebina, Takumi; Aleksic, Branko; Cabé, Nicolas; Savey, Véronique; Onoue, Takeshi; Yatsuya, Hiroshi","year":2025,"journal":"Clinical nutrition (Edinburgh, Scotland), 51, 252-265","doi":"10.1016/j.clnu.2025.06.011","pmid":"40617160","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12800","title":"Clinical Profile and Prognosis of Patients With Acute Decompensated Heart Failure Who Met the Obesity-Related Eligibility for Subcutaneous Semaglutide　- Findings From the CURE-HF Registry.","authors":"Nishikawa, Ken; Minamisawa, Masatoshi; Yoshie, Koji; Suzuki, Sho; Tanaka, Kiu; Okuma, Yukari; Kimura, Kazuhiro; Ueki, Yasushi; Oguchi, Yasutaka; Kato, Tamon; Saigusa, Tatsuya; Ebisawa, Soichiro; Okada, Ayako; Motoki, Hirohiko; Kuwahara, Koichiro","year":2025,"journal":"Circulation reports, 7(6), 463-472","doi":"10.1253/circrep.CR-25-0041","pmid":"40497126","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12801","title":"Role of a Bioelectrical Impedance Analysis in Predicting Anemia among Cardiovascular Disease Patients.","authors":"Nishikawa, Tomoaki; Higaki, Akinori; Okada, Yutaro; Horie, Rikako; Nakao, Yasuhisa; Fujisawa, Tomoki; Miyazaki, Shigehiro; Akazawa, Yusuke; Miyoshi, Toru; Kawakami, Hiroshi; Higashi, Haruhiko; Tamaki, Shunsuke; Nishimura, Kazuhisa; Inoue, Katsuji; Ikeda, Shuntaro; Yamaguchi, Osamu","year":2025,"journal":"Internal medicine (Tokyo, Japan), 64(17), 2534-2540","doi":"10.2169/internalmedicine.4824-24","pmid":"40090721","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12802","title":"Responses of B-type natriuretic peptide (BNP), mature BNP and proBNP to sacubitril/valsartan differs between responders and non-responders.","authors":"Nishikimi, Toshio; Nakagawa, Yasuaki; Miyamoto, Shoichi; Kanamori, Takahiko; Inazumi, Hideaki; Yanagisawa, Hiromu; Moriuchi, Kenji; Kinoshita, Hideaki; Tamamura, Yusuke; Takahama, Hiroyuki; Minamino, Naoto; Ono, Koh","year":2025,"journal":"Open heart, 12(1)","doi":"10.1136/openhrt-2024-002990","pmid":"39988342","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 54 heart failure patients treated with sacubitril/valsartan over 12 weeks:\n- Total BNP and BNPcom (commercial assay) did not change overall\n- NT-proBNP and proBNP decreased (reflecting hemodynamic improvement)\n- Mature BNP modestly increased (because neprilysin inhibition prevents its degradation)\n- ANP (A-type natriuretic peptide) greatly increased\n\nResponders (n=31, defined by NT-proBNP <70% of baseline at 12 weeks) showed smaller percentage changes in all natriuretic peptides than non-responders (n=23; all P<0.01). The percentage change in each natriuretic peptide at 4 weeks predicted responder status with AUC of approximately 0.80. Correlations between peptide levels at baseline and during treatment were strong and consistent.","whyItMatters":"Sacubitril/valsartan is a cornerstone heart failure treatment, but its mechanism of action (neprilysin inhibition) artificially raises mature BNP levels, confusing the BNP tests that cardiologists rely on to monitor treatment response. This study solves that puzzle by showing that different BNP forms respond in opposite directions and that standard BNP tests can still be used — challenging the prevailing belief that BNP monitoring is unreliable on this drug. The ability to predict responders at 4 weeks could help clinicians make faster treatment decisions.","specificNumbers":"","methodology":"Prospective study of 54 heart failure patients measured at baseline and at 2, 4, 8, and 12 weeks of sacubitril/valsartan treatment. Plasma mature BNP, proBNP, and total BNP were measured using a specialized immunochemiluminescent assay that distinguishes these forms. NT-proBNP, ANP, and conventional BNP (BNPcom) were measured with commercial assays. Responders were defined as NT-proBNP <70% of baseline at 12 weeks. ROC analysis assessed predictive ability of 4-week changes.","limitations":"The study included only 54 patients, limiting statistical power for subgroup analyses. The specialized BNP assay distinguishing mature BNP from proBNP is not widely available in clinical laboratories. The responder definition (NT-proBNP <70% of baseline) is somewhat arbitrary. The 12-week follow-up does not address longer-term peptide dynamics or clinical outcomes. The study did not assess whether BNP-guided management changes actually improve patient outcomes."},{"rthcId":"RPEP-12803","title":"Possible involvement of neuropeptide Y sub-receptor 1 (NPY-Y1) in the anti-viral response of SARS-CoV-2 infection in Syrian hamster.","authors":"Nishimura, Haruka; Araki, Kohei; Mitsuoka, Chihomi; Toriumi, Wataru; Kitajima, Shunichi; Takahashi, Eiki","year":2025,"journal":"Biomedical research (Tokyo, Japan), 46(2), 37-50","doi":"10.2220/biomedres.46.37","pmid":"40189329","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12804","title":"Serum Vasoactive Intestinal Peptide as a Novel Biomarker for Low-Voltage Areas in Patients With Atrial Fibrillation.","authors":"Nishino, Kotaro; Temma, Taro; Natsui, Hiroyuki; Watanabe, Masaya; Nakao, Motoki; Kawasaki, Masahiro; Shimano, Kintaro; Kawakami, Kei; Saito, Shota; Koya, Jiro; Tatsuta, Daishiro; Koizumi, Takuya; Kadosaka, Takahide; Koya, Taro; Tsuneta, Satonori; Kamiya, Kiwamu; Nagai, Toshiyuki; Anzai, Toshihisa","year":2025,"journal":"Journal of the American Heart Association, 14(7), e039192","doi":"10.1161/JAHA.124.039192","pmid":"40118798","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12805","title":"Advancements in Protein-Based Therapeutic Delivery Approaches Targeting the Blood-Brain Barrier and Insights on Computational Strategies.","authors":"Nithya, Radhakrishnan; Ramanathan, Muthiah","year":2025,"journal":"Critical reviews in therapeutic drug carrier systems, 42(6), 45-81","doi":"10.1615/CritRevTherDrugCarrierSyst.2025054214","pmid":"40921132","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12806","title":"Gastrointestinal and Hepatobiliary Safety of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes.","authors":"Niu, Chengu; Sun, Kefang; Zhang, Jing; Elkhapery, Ahmed; Zhu, Kaiwen; Malik, Sheza; Xue, Chao; Okolo, Patrick I","year":2025,"journal":"The American journal of gastroenterology","doi":"10.14309/ajg.0000000000003760","pmid":"40900093","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12807","title":"Metabolic and hepatic effects of semaglutide and empagliflozin on metabolic dysfunction-associated steatotic liver disease mice.","authors":"Niu, Shu; Chen, Shu-Chun; Wang, Chen-Xi; Yue, Lin; Wang, Shu-Qi","year":2025,"journal":"World journal of hepatology, 17(10), 110402","doi":"10.4254/wjh.v17.i10.110402","pmid":"41179732","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 32 mice divided into four groups (control, high-fat, semaglutide, empagliflozin), both semaglutide and empagliflozin significantly improved glycolipid metabolism, reduced inflammation and oxidative stress, and restored pathological liver structure compared to the high-fat group. No statistically significant differences were found between the two drugs for MASLD outcomes.\n\nMetabolomics revealed that both drugs reduced levels of several lysophosphatidylcholine (LPC) species in liver tissue, suggesting the liver-protective effects may be mediated through LPC modulation.","whyItMatters":"Metabolic dysfunction-associated steatotic liver disease (MASLD, formerly NAFLD) affects roughly a quarter of the global population and has no approved cure. Semaglutide is already being studied in human MASLD trials, and this study reveals a potential mechanism — LPC modulation — that could explain its liver benefits and guide development of more targeted therapies.","specificNumbers":"","methodology":"32 mice were randomly assigned to four groups: control, high-fat diet, semaglutide treatment, and empagliflozin treatment. Researchers assessed body weight changes, blood sugar and lipid profiles, inflammatory and oxidative stress markers, liver histopathology, and performed metabolomics analysis to identify molecular changes associated with treatment effects.","limitations":"This is a mouse study with a small sample size (8 per group), limiting statistical power. The high-fat diet model may not fully replicate human MASLD pathogenesis. The metabolomics findings are associative and don't prove LPC reduction is the causal mechanism. Drug doses and treatment duration were not specified in the abstract. Human studies are needed to confirm these mechanisms and the comparative effectiveness of the two drugs."},{"rthcId":"RPEP-12808","title":"Multi-omics analysis of hepatic outcomes in T2DM-MAFLD patients treated with semaglutide: a single-centre, longitudinal, data-driven study.","authors":"Niu, Shu; Chen, Shuchun; Wu, Di; Wang, Chenxi; Xu, Jianchao; Yin, Jiantong; Zhao, Yubin","year":2025,"journal":"Frontiers in endocrinology, 16, 1650729","doi":"10.3389/fendo.2025.1650729","pmid":"41103643","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12809","title":"Protein biomarkers in pulmonary arterial hypertension: advances, clinical relevance, and translational challenges.","authors":"Niu, Yanqin; Tian, Jinglin; Provencher, Steeve; Bonnet, Sebastien; Boucherat, Olivier; Potus, François; Gou, Deming","year":2025,"journal":"Journal of translational medicine, 23(1), 1288","doi":"10.1186/s12967-025-07257-w","pmid":"41239459","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12810","title":"Combining SNAC and C10 in oral tablet formulations for gastric peptide delivery: A preclinical and clinical study.","authors":"Niu, Zhigao; La Zara, Damiano; Blaabjerg, Lasse; Pessi, Jenni; Raptis, Konstantinos; Toftlev, Anders; Sauter, Max; Christophersen, Philip; Bardonnet, Pierre-Louis; Andersson, Vincent; Wu, Jian Xiong; Brandt, Matthäus; Fan, Li; Wang, Zhuoran; Hubálek, Franta; Wahlund, Per-Olof; Norrman, Mathias; Breusova, Kateryna; Hjaltason, Marie Stine; Mortensen, Nicolai Rytter; Bardtrum, Lars; Nissen, Birgitte; Naelapää, Kaisa; Sassene, Philip Jonas","year":2025,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 378, 92-102","doi":"10.1016/j.jconrel.2024.11.078","pmid":"39645088","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12811","title":"The outcomes of electronic personal health records in patients with heart failure or coronary artery disease.","authors":"Nochioka, Kotaro; Yasuda, Satoshi; Shiroto, Takashi; Yamamoto, Saori; Sato, Haruka; Hasebe, Yuhi; Godo, Shigeo; Nakano, Makoto; Shindo, Tomohiko; Nishimiya, Kensuke; Hao, Kiyotaka; Takahashi, Jun; Ido, Keisuke; Kakuta, Yoichi; Shimizu, Hiroaki; Shimokawa, Hiroaki; Nakayama, Masaharu","year":2025,"journal":"ESC heart failure, 12(2), 1464-1468","doi":"10.1002/ehf2.15079","pmid":"39543917","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12812","title":"Effectiveness, safety, and impact on multiple sclerosis course of anti-CGRP monoclonal antibodies.","authors":"Nociti, Viviana; Romozzi, Marina; Annovazzi, Pietro; Fantozzi, Roberta; Tortorella, Carla; Vercellino, Marco; Iannone, Luigi Francesco; De Luca, Giovanna; Tomassini, Valentina; Di Filippo, Massimiliano; Lorefice, Lorena; Maniscalco, Giorgia Teresa; Paolicelli, Damiano; Pinardi, Federica; Ronzoni, Marco; Solaro, Claudio Marcello; Gasperini, Claudio; Calabresi, Paolo; Vollono, Catello; Cocco, Eleonora","year":2025,"journal":"Journal of the neurological sciences, 469, 123392","doi":"10.1016/j.jns.2025.123392","pmid":"39808882","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Monthly headache days decreased significantly from 22.0 to 11.5 days (p=0.002) during concurrent treatment with anti-CGRP monoclonal antibodies and MS disease-modifying therapies.\n\nMS disability scores (EDSS) remained stable at 1.9 throughout the study period — from the year before starting anti-CGRP treatment through the last follow-up. Only two patients (8%) experienced a clinical MS relapse and one (4%) showed MRI activity during the treatment period. Mild adverse events occurred in just two patients (8%), and none led to discontinuation of the anti-CGRP therapy.","whyItMatters":"Migraine is extremely common in MS patients, but doctors have been cautious about combining anti-CGRP migraine drugs with MS immunotherapies due to concerns about drug interactions or worsening MS. This study provides reassuring real-world evidence that the combination is both safe and effective, potentially opening up better migraine management for a large population that suffers disproportionately from both conditions.","specificNumbers":"","methodology":"This was a retrospective, multicenter study conducted across 14 MS centers. Researchers reviewed records of 25 MS patients who were receiving both anti-CGRP monoclonal antibodies for migraine and stable disease-modifying therapies for their MS. They tracked MS outcomes (relapses, disability scores, MRI activity) and migraine outcomes (monthly headache days, painkiller use) from one year before starting anti-CGRP treatment through the last follow-up visit.","limitations":"The study had a small sample size of only 25 patients, which limits statistical power to detect rare adverse events or subtle effects on MS progression. The retrospective design means researchers relied on existing medical records rather than prospective, controlled observation. There was no placebo control group, so the natural fluctuation of both migraine and MS symptoms could influence results. Follow-up duration varied across patients."},{"rthcId":"RPEP-12813","title":"Medications for adults with type 2 diabetes: a living systematic review and network meta-analysis.","authors":"Nong, Kailei; Jeppesen, Britta Tendal; Shi, Qingyang; Agoritsas, Thomas; Guyatt, Gordon H; White, Heath; Gao, Yiyuan; Agarwal, Arnav; Macdonald, Helen; Zou, Xinyu; Millard, Tanya; Schnell, Oliver; Marx, Nikolaus; Brosius, Frank C; McDonald, Steve; Quigley, Matthew; Tian, Xin; Fan, Qinlin; White, Barbara; Mao, Yunhe; Pan, Xiaohui; Liu, Changhai; Zhai, Chunjuan; Yuan, Chi; Li, Qiang; An, Jing; Gan, Yu; Wang, Yanyan; Jin, Yinghui; Sun, Feng; Zhu, Zhiming; Rydén, Lars; Standl, Eberhard; Turner, Tari; Vandvik, Per Olav; Li, Sheyu","year":2025,"journal":"BMJ (Clinical research ed.), 390, e083039","doi":"10.1136/bmj-2024-083039","pmid":"40813122","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"From 869 trials with 493,168 participants covering 63 drugs across 13 classes:\n\nWeight loss leaders: tirzepatide (-8.63 kg, moderate certainty) and orforglipron (-7.87 kg, low certainty), followed by 8 other GLP-1 RAs (high to moderate certainty).\n\nCardiovascular/kidney benefits: SGLT-2 inhibitors, GLP-1 RAs, and finerenone confirmed with moderate to high certainty evidence.\n\nKey harms: tirzepatide and GLP-1 RAs probably increase severe gastrointestinal events (tirzepatide OR 4.21, moderate certainty). SGLT-2 inhibitors increase genital infections (OR 3.29) and ketoacidosis (OR 2.08). Sulfonylureas and insulin increase hypoglycemia.\n\nUncertainty remains about whether GLP-1 RAs reduce dementia (OR 0.92, low certainty) and effects on neuropathy and visual impairment.","whyItMatters":"With millions of people taking diabetes medications and billions in annual drug spending, clinicians need reliable comparative evidence to guide treatment decisions. This living NMA provides the most comprehensive drug comparison available, with risk-stratified absolute effects that allow doctors to match drug choice to each patient's cardiovascular and kidney risk profile. The confirmation that peptide-based therapies (GLP-1 RAs, tirzepatide) lead for weight loss while providing cardiovascular benefits — offset by gastrointestinal harms — is essential information for the growing population using these drugs.","specificNumbers":"","methodology":"Living systematic review and network meta-analysis using frequentist random effects models and GRADE evidence assessment. Medline and Embase searched through July 2024. Included 869 randomized controlled trials (≥24 weeks) comparing diabetes medications with standard treatment, placebo, or each other. 493,168 participants, 13 drug classes (63 drugs), and 26 outcomes analyzed. Risk-stratified absolute effects generated via interactive tool. Registered on PROSPERO (CRD42022325948). Updates planned at least twice yearly.","limitations":"Despite 869 trials, evidence for some outcomes (neuropathy, visual impairment, dementia) remains low certainty. The NMA methodology relies on indirect comparisons where head-to-head data are unavailable. The search through July 2024 may miss recent trials. Not all drug combinations were evaluable. The gastrointestinal harm analysis may not fully capture the dose-titration strategies that mitigate side effects in clinical practice. Cost-effectiveness was not assessed."},{"rthcId":"RPEP-12814","title":"Development of Antimicrobial Peptide-loaded Hydrogels as Potential Scaffolds for Pulp-dentine Complex Regeneration: A Comparative Study.","authors":"Noohi, Parisa; Abdekhodaie, Mohammad J; Nekoofar, Mohammad H; Gama, Miguel; Saadatmand, Maryam; Dummer, Paul M H","year":2025,"journal":"Journal of endodontics, 51(5), 585-593","doi":"10.1016/j.joen.2025.01.018","pmid":"39914769","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12815","title":"Real-World Use of GLP-1 Receptor Agonist Liraglutide in Adolescents with Obesity: A First Longitudinal Single-Center Analysis from Switzerland.","authors":"Noordam, Cees; Eiholzer, Urs; Katschnig, Claudia; Stasinaki, Aikaterini; Dubinski, Ilja","year":2025,"journal":"Children (Basel, Switzerland), 12(12)","doi":"10.3390/children12121716","pmid":"41462856","tags":[],"studyType":"observational","evidenceStrength":"low-moderate","keyFinding":"In a real-world Swiss clinic, 22 adolescents with obesity treated with liraglutide (Saxenda) showed significant BMI reduction comparable to clinical trial results. BMI-SDS dropped from +2.63 to +2.40 (median reduction -0.20, p=0.0003) with a large effect size (rb = -0.77).\n\nHowever, 13 of 22 patients (59%) discontinued treatment — mainly due to insufficient weight loss or mild nausea. Among the 9 who continued, results were more impressive: BMI-SDS dropped from +2.59 to +2.08. No serious adverse events occurred. The mean treatment duration was only 8.2 months, and 15 of 22 patients had Southern European immigrant backgrounds.","whyItMatters":"Clinical trials paint an optimistic picture of GLP-1 drugs, but real-world results often differ because patients don't receive the intensive lifestyle support provided in trials. This is one of the first studies showing how liraglutide actually performs in a typical adolescent clinic setting. The good news: it works about as well as in trials. The bad news: nearly 60% of teens stopped taking it within 18 months. This highlights that the biggest challenge with GLP-1 drugs in adolescents isn't efficacy — it's keeping them on the medication long enough to benefit.","specificNumbers":"n=22 · mean age 14.9 years · BMI-SDS +2.63→+2.40 · median reduction -0.20 · p=0.0003 · rb=-0.77 · 59% discontinued · mean duration 8.2 months · continuers: +2.59→+2.08 · no serious adverse events","methodology":"Retrospective longitudinal non-interventional study at a single Swiss pediatric endocrinology center. 22 adolescents (ages 12.5–17.5) treated with liraglutide received non-structured nutritional/lifestyle counseling with three-monthly follow-up. BMI-SDS and adverse effects were tracked over the treatment period (mean 8.2 months, range 1–18 months).","limitations":"Very small sample (n=22) at a single center. No control group. Retrospective design. Non-structured lifestyle counseling may not reflect other clinical settings. High discontinuation rate (59%) limits conclusions about sustained efficacy. Short mean treatment duration (8.2 months). The predominantly Southern European immigrant population limits generalizability."},{"rthcId":"RPEP-12816","title":"In vivo Pharmacokinetic and ADMET Profiles of Synthetic Antimicrobial Peptides (AMPs).","authors":"Noordin, Muhammad Akram Mohd; Najm, Ahmed Abdulkareem; Dyari, Herryawan Ryadi Eziwar; Law, Douglas; Alwi, Sharifah Sakinah Syed; Lazim, Azwan Mat; Cheah, Yew Hoong; Tee, Thiam Tsui; Fazry, Shazrul","year":2025,"journal":"Mini reviews in medicinal chemistry, 25(8), 579-590","doi":"10.2174/0113895575362479241231054240","pmid":"39950486","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12817","title":"Beyond weight loss: tirzepatide as a dual GIP/GLP-1 receptor agonist for obstructive sleep apnea.","authors":"Noreña, Jairo A; Akcan, Tugce; Desai, Dimpi","year":2025,"journal":"Current opinion in endocrinology, diabetes, and obesity","doi":"10.1097/MED.0000000000000949","pmid":"41405280","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12818","title":"Comparison of Fracture Risk Following Semaglutide Treatment vs Sleeve Gastrectomy.","authors":"Noreña, Jairo A; Pike, C William; Hui, Gavin; Motlaghzadeh, Yasaman; Sellmeyer, Deborah E; Wu, Joy Y; Kim, Sun H","year":2025,"journal":"AACE endocrinology and diabetes, 12(4), 308-313","doi":"10.1016/j.aed.2025.10.001","pmid":"41467149","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"From a dataset representing over 161 million US patients, 92,405 semaglutide users and 16,082 sleeve gastrectomy patients were identified. After high-dimensional propensity score matching, 2,887 individuals were compared in each group. Over a mean follow-up of 3 years, the semaglutide group had 86 fractures (2.98%) versus 128 fractures (4.43%) in the surgery group.\n\nThis translated to a hazard ratio of 0.74 (95% CI: 0.56-0.98), meaning semaglutide users had a statistically significant 26% lower fracture risk. Both groups were well-matched: mean age 45, predominantly female (~78%), similar comorbidity burden (Charlson Index 1.9), and similar racial composition.","whyItMatters":"As millions of patients use GLP-1 receptor agonists for weight loss, understanding their effect on bone health is critical. Bariatric surgery is known to increase fracture risk through mechanisms including rapid weight loss, reduced mechanical loading, and nutrient malabsorption. This study provides the first large-scale real-world comparison suggesting semaglutide may preserve bone health better than surgery during weight loss — an important consideration when choosing between treatment modalities.","specificNumbers":"","methodology":"Retrospective cohort study using the Atropos Eos electronic health record dataset (2016-2023), covering community hospitals and large practices across the US. Adults with obesity treated with either semaglutide or sleeve gastrectomy were included. High-dimensional propensity score matching was used to reduce confounding between groups. Fracture outcomes were compared using hazard ratios.","limitations":"This is a retrospective observational study, so it cannot prove causation. Despite propensity score matching, unmeasured confounders (such as degree of weight loss, physical activity, calcium/vitamin D intake, or bone density at baseline) could influence results. The E-value of 1.2 suggests the findings could be explained by modest unmeasured confounding. The study could not distinguish between fracture types or determine whether the benefit was driven by fewer falls or better bone quality. Semaglutide dosing and indication (diabetes vs. weight loss) were not differentiated."},{"rthcId":"RPEP-12819","title":"The combination of zalfermin and semaglutide has additive therapeutic effects in a diet-induced obese and biopsy-confirmed mouse model of MASH.","authors":"Norlin, Jenny; Dermit, Maria; Sidiropoulos, Nikos; Galsgaard, Elisabeth D; Hansen, Henrik H; Feigh, Michael; Veidal, Sanne S; Latta, Markus; Henriksson, Emma; Andersen, Birgitte","year":2025,"journal":"PloS one, 20(10), e0331665","doi":"10.1371/journal.pone.0331665","pmid":"41150667","tags":[],"studyType":"animal","evidenceStrength":"preliminary","keyFinding":"Combining low-dose zalfermin (an FGF21 analog) with low-dose semaglutide produced super-additive weight loss of 18% in MASH mice — far exceeding either drug alone at the same doses (zalfermin -6%, semaglutide -4%). The combination was equally effective as high doses of either drug given alone.\n\nBeyond weight, the low-dose combination improved liver enzymes, cholesterol, triglycerides, liver inflammation score (NAS), steatosis, and fibrosis gene expression markers more than either low-dose monotherapy and more than high-dose semaglutide alone. This supports combining FGF21 analogs with GLP-1 drugs for MASH treatment.","whyItMatters":"MASH (formerly NASH) is the most common liver disease globally and a leading cause of liver transplants, yet treatment options are limited. GLP-1 drugs like semaglutide help with weight loss but have modest direct liver effects. FGF21 analogs like zalfermin directly target liver metabolism but don't produce much weight loss. Combining them addresses both problems at lower doses, potentially reducing side effects while maximizing liver benefit — a strategy now entering clinical trials.","specificNumbers":"n=11-12 per group · Combination weight loss: -18% · Zalfermin alone (low): -6% · Semaglutide alone (low): -4% · High-dose zalfermin: -16% · High-dose semaglutide: -15% · 8-week treatment · Biopsy-confirmed MASH model","methodology":"Used Amylin liver NASH diet-induced obese mice with biopsy-confirmed MASH and fibrosis. Groups received daily subcutaneous vehicle, low or high-dose zalfermin, low or high-dose semaglutide, or low-dose combination for 8 weeks. Pre- and post-treatment liver biopsies allowed within-subject comparison. Endpoints: body weight, plasma/liver biochemistry, NAS scoring, fibrosis staging, quantitative histology, and liver RNA sequencing.","limitations":"Mouse model study — MASH drug responses in mice don't always translate to humans. The AMLN diet model creates MASH through extreme diet manipulation, which differs from human disease development. Only 8-week treatment duration; chronic liver disease may require longer treatment. Specific dose ratios that are optimal in mice may not translate directly to human dosing. Only one combination dose ratio was tested."},{"rthcId":"RPEP-12820","title":"Optimizing GLP-1 therapies for obesity and diabetes management.","authors":"Noronha, Jarvis C; Van Gaal, Luc F; Neeland, Ian J; Fitch, Angela; Pfeiffer, Andreas Fh; Chiavaroli, Laura; Kendall, Cyril Wc; Sievenpiper, John L","year":2025,"journal":"Obesity pillars, 16, 100222","doi":"10.1016/j.obpill.2025.100222","pmid":"41322078","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12821","title":"Management of Type 2 Diabetes Mellitus in Native Americans and Alaska Natives: A Systematic Review.","authors":"Norris, Quintin; Brandt, Mckenzie D; Nagy, Stephanie; Kesselman, Marc; Demory, Michelle L","year":2025,"journal":"Journal of racial and ethnic health disparities","doi":"10.1007/s40615-025-02668-3","pmid":"40971128","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12822","title":"Effects of Resmetirom on Metabolic-Dysfunction Associated Steatohepatitis in Patients With Weight Loss and/or Diabetes Taking Glucagon-Like Peptide-1 Receptor Agonists and Other Diabetes Therapies: A Secondary Analysis of the MAESTRO-NASH Trial.","authors":"Noureddin, Mazen; Rinella, Mary; Taub, Rebecca; Labriola, Dominic; Camacho, Raul C; Alkhouri, Naim; Loomba, Rohit; Bansal, Meena B","year":2025,"journal":"Alimentary pharmacology & therapeutics, 62(11-12), 1089-1099","doi":"10.1111/apt.70382","pmid":"41127972","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In a secondary analysis of the MAESTRO-NASH phase 3 trial, resmetirom (80 or 100 mg) maintained its efficacy on histological and biomarker endpoints regardless of background GLP-1 RA or SGLT2i therapy. Rates of MASH resolution and fibrosis improvement were similar between patients on and off these diabetes medications. Notably, resmetirom 100 mg patients achieving ≥5% weight loss showed superior outcomes: MASH resolution 56.6% vs. 33.8%, fibrosis improvement 40.6% vs. 31.5%, MRI-PDFF reduction -69% vs. -46%, and liver stiffness reduction -4.6 kPa vs. -2.3 kPa at 52 weeks.","whyItMatters":"Many patients with fatty liver disease also have type 2 diabetes and are taking GLP-1 receptor agonists like semaglutide. This analysis confirms that resmetirom — the first FDA-approved drug specifically for MASH — can be safely combined with these peptide therapies without losing effectiveness. The finding that weight loss enhances resmetirom's benefits further supports combining it with weight-reducing GLP-1 drugs.","specificNumbers":"","methodology":"This was a pre-specified secondary analysis of MAESTRO-NASH, a randomized, double-blind, placebo-controlled, 54-month phase 3 trial (NCT03900429). Patients had biopsy-confirmed MASH with liver fibrosis. Week 52 histological endpoints (MASH resolution, fibrosis improvement) and biomarker endpoints (MRI-PDFF, liver stiffness) were analyzed by background diabetes therapy status (GLP-1 RA, SGLT2i) and weight loss (≥5% vs. <5%).","limitations":"This is a secondary analysis, not a trial specifically designed to test the combination. Only 13-17% of participants were on GLP-1 RA or SGLT2i therapy, limiting statistical power for subgroup comparisons. Background GLP-1 RA therapy did not produce additional weight loss in this cohort, which may not reflect typical GLP-1 RA treatment effects. The 52-week timepoint may not capture longer-term outcomes."},{"rthcId":"RPEP-12823","title":"Cardiac risk assessment after noncardiac surgery: a historical cohort study on guideline adherence at a Canadian quaternary care centre.","authors":"Noutsios, Dean; Marino, Amanda; Anacleto-Dabarno, Matthew; Baldini, Gabriele; Bessissow, Amal","year":2025,"journal":"Canadian journal of anaesthesia = Journal canadien d'anesthesie, 72(12), 1719-1728","doi":"10.1007/s12630-025-03040-z","pmid":"41326931","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12824","title":"Manufacturing and Financial Evaluation of Peptide-Based Neoantigen Cancer Vaccines for Triple-Negative Breast Cancer in the United Kingdom: Opportunities and Challenges.","authors":"Novakova, Adriana; Morris, Stephen A; Vaiarelli, Ludovica; Frank, Stefanie","year":2025,"journal":"Vaccines, 13(2)","doi":"10.3390/vaccines13020144","pmid":"40006691","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12825","title":"One small molecule for man, one giant leap for mankind with obesity.","authors":"Novikoff, Aaron; Müller, Timo D","year":2025,"journal":"Med (New York, N.Y.), 6(12), 100924","doi":"10.1016/j.medj.2025.100924","pmid":"41389711","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12826","title":"Botulinum Toxin Effects on Biochemical Biomarkers Related to Inflammation-Associated Head and Neck Chronic Conditions: A Systematic Review of Preclinical Research.","authors":"Novo Pereira, Ines; De la Torre Canales, Giancarlo; Durão, Sara; Shado, Rawand; Braga, Ana Cristina; Almeida, André Mariz; Hassan, Haidar; Manso, Ana Cristina; Faria-Almeida, Ricardo","year":2025,"journal":"Toxins, 17(8)","doi":"10.3390/toxins17080377","pmid":"40864053","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12827","title":"Botulinum toxin effects on biochemical biomarkers related to inflammation-associated head and neck chronic conditions: a systematic review of clinical research.","authors":"Novo Pereira, Ines; Durão, Sara; Hassan, Haidar; Braga, Ana Cristina; Mariz Almeida, André; Manso, Ana Cristina; Faria-Almeida, Ricardo; De la Torre Canales, Giancarlo","year":2025,"journal":"Journal of neural transmission (Vienna, Austria : 1996), 132(12), 1851-1874","doi":"10.1007/s00702-024-02869-w","pmid":"40035830","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12828","title":"Vagal Oxytocin Receptors as Molecular Targets in Gut-Brain Signaling: Implications for Appetite, Satiety, Obesity, and Esophageal Motility-A Narrative Review.","authors":"Nowacka, Agnieszka; Śniegocki, Maciej; Ziółkowska, Ewa A","year":2025,"journal":"International journal of molecular sciences, 26(16)","doi":"10.3390/ijms26167812","pmid":"40869135","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12829","title":"From steatosis to cirrhosis: the role of obesity in the progression of liver disease.","authors":"Nowak, Klaudia; Paluch, Maria; Cudzik, Maja; Syska, Klaudia; Gawlikowska, Wiktoria; Janczura, Jakub","year":2025,"journal":"Journal of diabetes and metabolic disorders, 24(2), 227","doi":"10.1007/s40200-025-01754-x","pmid":"41104308","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12830","title":"Therapeutic Potential of GLP-1 Receptor Agonists in Metabolic Associated Steatotic Liver Disease.","authors":"Nowak, Klaudia; Łupina, Krzysztof; Romac, Anna; Kalisz, Aleksandra; Ilkiewicz, Łucja; Janczura, Jakub","year":2025,"journal":"The Annals of pharmacotherapy, 59(10), 928-936","doi":"10.1177/10600280251322002","pmid":"40072011","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12831","title":"Various GLP-1 Receptor Agonist Preference Use with a Special Focus on Oral and Subcutaneous Forms in Poland.","authors":"Nowak, Klaudia; Dziewierz, Artur; Sojda, Aleksandra; Zabojszcz, Michał; Szarpak, Łukasz; Dardzinska, Natalia; Jaskulska, Paulina; Siudak, Zbigniew","year":2025,"journal":"Healthcare (Basel, Switzerland), 13(22)","doi":"10.3390/healthcare13222874","pmid":"41302262","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 receptor agonist use in Poland increased from 212 patients in 2018 to 12,836 in 2024. Obesity was the primary diagnosis in 78% of all patients, with the highest rates in liraglutide and tirzepatide users. The dulaglutide group had the highest rate of type 2 diabetes (67%), while tirzepatide users had the lowest (15%).\n\nOral semaglutide's share grew steadily from 2022, reaching 50% of all semaglutide applications by 2024. Oral semaglutide users tended to be younger females with less aggravating medical history compared to those on injectable forms.","whyItMatters":"This study captures a real-world snapshot of how GLP-1 drug prescribing has evolved in a major European market. The rapid shift toward oral semaglutide and the dominance of obesity as the primary treatment indication reflect broader global trends in how these peptide-based medications are being used, moving beyond their original diabetes focus.","specificNumbers":"","methodology":"A cohort study using anonymized medical records from 300 outpatient clinics belonging to Luxmed, the largest private healthcare network in Poland. Researchers identified all consecutive patients with at least one GLP-1 RA prescription between January 2018 and December 2024, analyzing clinical characteristics, diagnoses, and prescription patterns.","limitations":"Data came from a single private healthcare network (Luxmed) in Poland, which may not represent prescribing patterns in public healthcare or other countries. The study tracked prescriptions rather than outcomes, so it cannot speak to effectiveness or side effects. The dramatic growth may partly reflect increased drug availability and awareness rather than purely clinical need."},{"rthcId":"RPEP-12832","title":"The quantity, quality and findings of network meta-analyses evaluating the effectiveness of GLP-1 RAs for weight loss: a scoping review.","authors":"Nunns, Michael; Febrey, Samantha; Buckland, Jill; Abbott, Rebecca; Whear, Rebecca; Bethel, Alison; Boddy, Kate; Shaw, Liz; Coon, Jo Thompson; Melendez-Torres, G J","year":2025,"journal":"Health technology assessment (Winchester, England), 1-73","doi":"10.3310/SKHT8119","pmid":"40580049","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12833","title":"Enteroendocrine cells regulate intestinal barrier permeability.","authors":"Nwako, Jennifer G; Patel, Sparsh D; Roach, Taevon J; Gupte, Saanvi R; Williams, Samara G; Riedman, Anne Marie; McCauley, Heather A","year":2025,"journal":"American journal of physiology. Cell physiology, 328(5), C1501-C1508","doi":"10.1152/ajpcell.01077.2024","pmid":"40095977","tags":["pyy","somatostatin","gut-barrier"],"studyType":"in-vitro","evidenceStrength":"moderate","keyFinding":"Enteroendocrine cells — hormone-producing cells in the gut lining — are required to maintain a healthy intestinal barrier. When human intestinal organoids were genetically engineered to lack these cells, barrier function deteriorated in both stem cell-like and mature tissue. Adding the peptide hormones PYY (peptide tyrosine-tyrosine) and octreotide (a somatostatin analog) rescued barrier function both at baseline and in the presence of the inflammatory cytokine TNF. Surprisingly, the barrier improvement occurred without significant changes in tight junction protein levels, suggesting a novel mechanism.","whyItMatters":"There are currently no drugs that directly strengthen the intestinal barrier — a central problem in inflammatory bowel disease, where a leaky gut drives a cycle of worsening inflammation. This study reveals that gut hormones PYY and somatostatin can directly improve barrier integrity, opening an entirely new therapeutic avenue for IBD and other conditions involving intestinal permeability.","specificNumbers":"PYY and octreotide rescued barrier defects · Barrier improvement occurred independently of tight junction protein (ZO-1, occludin, claudin-2) changes · Effective both at baseline and under TNF-induced inflammation","methodology":"Researchers grew human intestinal enteroids (miniature gut tissue models) on Transwell filters. They used genetic knockout to remove enteroendocrine cells and measured barrier function via transepithelial electrical resistance and paracellular permeability assays. They then supplemented the EEC-deficient cultures with PYY and octreotide to test whether these hormones could restore barrier function. Tight junction proteins were assessed by immunostaining and abundance measurements.","limitations":"This is an in-vitro study using human intestinal organoids, not living patients. While organoids are more representative than cell lines, they lack the immune cells, blood vessels, and microbiome present in a real gut. The study did not test other enteroendocrine hormones (like GLP-1 or GLP-2) that might also contribute. Dosing and timing that would be effective in human IBD patients are unknown."},{"rthcId":"RPEP-12834","title":"Pathophysiology and emerging biomarkers of cardiovascular-renal-hepato-metabolic syndrome.","authors":"Nzobokela, John; Muchaili, Lweendo; Mwambungu, Alick; Masenga, Sepiso K; Kirabo, Annet","year":2025,"journal":"Frontiers in cardiovascular medicine, 12, 1661563","doi":"10.3389/fcvm.2025.1661563","pmid":"41235339","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies several emerging biomarkers for Cardiovascular-Renal-Hepatic-Metabolic (CRHM) syndrome that outperform traditional inflammatory markers like CRP and IL-6. Soluble urokinase plasminogen activator receptor (suPAR) is highlighted as a stable predictor of systemic inflammation linked to CKD, atherosclerosis, and coronary artery disease. Galectin-3 regulates fibrosis and inflammation across multiple organs. Growth Differentiation Factor-15 (GDF-15) indicates mitochondrial dysfunction and cardiovascular aging. MicroRNAs miR-126 and miR-423-5p show promise for tracking vascular integrity and heart failure progression.\n\nThese biomarkers support targeted use of SGLT2 inhibitors for cardiorenal protection and GLP-1 receptor agonists or dual GIP/GLP-1 agonists for metabolic and liver-related complications.","whyItMatters":"Heart, kidney, liver, and metabolic diseases rarely exist in isolation — they drive each other in a vicious cycle that current medicine often treats organ by organ. This framework pushes for integrated diagnosis and treatment, with biomarkers that capture the multi-organ nature of disease. Linking these biomarkers to specific therapies like GLP-1 agonists could move medicine toward truly personalized multi-organ care.","specificNumbers":"","methodology":"Narrative review analyzing the pathophysiology of CRHM syndrome and evaluating emerging biomarkers based on published literature. The review synthesizes evidence on disease mechanisms (chronic inflammation, insulin resistance, oxidative stress, endothelial dysfunction) and assesses the clinical utility of novel biomarkers for risk stratification and treatment guidance.","limitations":"As a narrative review, this paper synthesizes existing evidence but does not generate new data. The clinical integration of the discussed biomarkers remains limited — most are not yet standard in clinical practice. The review does not provide specific thresholds or cutoff values for when biomarker levels should trigger particular treatments. Long-term prospective validation studies are needed for most of the emerging biomarkers discussed."},{"rthcId":"RPEP-12835","title":"Effect of Liraglutide on Intermittent Hypoxia-Induced Metabolic Dysfunction: From Bench to Bedside.","authors":"O'Donnell, Cliona; King, Ailbhe; Vial, Guillaume; O'Neill, Emily; Crilly, Shane; Dodd, Jonathan D; Murphy, David J; Belaidi, Elise; Pepin, Jean-Louis; Arnaud, Claire; O'Shea, Donal; Ryan, Silke","year":2025,"journal":"Journal of sleep research, e70152","doi":"10.1111/jsr.70152","pmid":"40718907","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12836","title":"Anti-consumption agents: Tirzepatide and semaglutide for treating obesity-related diseases and addictions, and improving life expectancy.","authors":"O'Keefe, James H; Franco, W Grant; O'Keefe, Evan L","year":2025,"journal":"Progress in cardiovascular diseases, 89, 102-112","doi":"10.1016/j.pcad.2024.12.010","pmid":"39743126","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12837","title":"Development of Cell-Penetrating Peptides and Their Application to DDS.","authors":"Oba, Makoto","year":2025,"journal":"Chemical & pharmaceutical bulletin, 73(7), 574-580","doi":"10.1248/cpb.c25-00272","pmid":"40603108","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12838","title":"Receptor-mediated Gi-3 activation in mammalian and human brain membranes: Reestablishment method and its application to nociceptin/orphanin FQ opioid peptide (NOP) receptor/Gi-3 interaction.","authors":"Odagaki, Yuji; Kinoshita, Masakazu; Honda, Makoto; Meana, J Javier; Callado, Luis F; García-Sevilla, Jesús A; Palkovits, Miklós; Borroto-Escuela, Dasiel Oscar; Fuxe, Kjell","year":2025,"journal":"Journal of pharmacological sciences, 158(2), 131-138","doi":"10.1016/j.jphs.2025.03.014","pmid":"40288823","tags":["nociceptin","opioid-peptides","receptor-pharmacology"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Researchers reestablished a specialized lab assay (GTPγS binding/immunoprecipitation) to measure how the nociceptin/orphanin FQ peptide activates a specific signaling protein called Gαi-3 in brain tissue. Using rat and postmortem human brain membranes, they showed that nociceptin increased Gαi-3 activation in a dose-dependent manner.\n\nImportantly, the nociceptin response was not blocked by naloxone (a classical opioid antagonist), confirming that the NOP receptor operates through a distinct mechanism from traditional opioid receptors. However, the selective NOP antagonist J-113397 potently inhibited the response, validating receptor specificity.","whyItMatters":"Understanding how nociceptin selectively couples to specific G-protein subtypes helps explain why this peptide system modulates pain, anxiety, and reward differently from classical opioids. This method enables researchers to study 'functional selectivity' — the concept that different drugs can activate the same receptor but trigger different downstream signals — which is critical for developing safer pain medications.","specificNumbers":"","methodology":"In vitro study using rat and postmortem human brain membranes. Researchers screened commercially available anti-Gαi-3 antibodies, selected the most effective one, optimized assay conditions, then tested multiple agonists including nociceptin. Receptor specificity was confirmed using naloxone and the selective NOP antagonist J-113397.","limitations":"In vitro study using brain membrane preparations, not living tissue or whole organisms. Used postmortem human brain tissue, which may not perfectly reflect living brain signaling. The method requires specialized equipment and reagents, limiting widespread adoption."},{"rthcId":"RPEP-12839","title":"Emerging role of GLP-1 agonists in cardio-metabolic therapy - Focus on Semaglutide.","authors":"Odigwe, Celestine; Mulyala, Rajasekhar; Malik, Haijra; Ruiz, Brent; Riad, Mariam; Sayiadeh, Mohammad As; Honganur, Sanchitha; Parks, Alexis; Rahman, Mustafeez Ur; Lakkis, Nasser","year":2025,"journal":"American heart journal plus : cardiology research and practice, 52, 100518","doi":"10.1016/j.ahjo.2025.100518","pmid":"40115122","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12840","title":"Case Report: Amelioration of severe metabolic dysfunction-associated steatohepatitis after switching from conventional GLP-1RAs to tirzepatide.","authors":"Oe, Yuki; Omori, Takashi; Aimono, Eriko; Furukawa, Shin; Kitakawa, Hirohiko; Tateno, Masatoshi; Sakai, Kiyoshi; Cho, Kyu Yong","year":2025,"journal":"Frontiers in endocrinology, 16, 1501984","doi":"10.3389/fendo.2025.1501984","pmid":"40491599","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12841","title":"Effect of Beta-Cell Function on Glucose Variability When Switching From Insulin Degludec Plus a Dipeptidyl Peptidase-4 Inhibitor to Insulin Degludec/Liraglutide: Preliminary Results From a Pilot Study.","authors":"Oe, Yuki; Nomoto, Hiroshi; Nakamura, Akinobu; Kuwabara, Saki; Takahashi, Yuka; Yasui, Ayano; Izumihara, Rimi; Miya, Aika; Kameda, Hiraku; Cho, Kyu Yong; Atsumi, Tatsuya","year":2025,"journal":"International journal of endocrinology, 2025, 3911323","doi":"10.1155/ije/3911323","pmid":"41376852","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12842","title":"Efficacy and safety of tirzepatide in subjects with type 2 diabetes and chronic kidney disease: a prospective, two-arm observational study.","authors":"Oe, Yuki; Nomoto, Hiroshi; Cho, Kyu Yong; Omori, Takashi; Nakamura, Koki; Takahashi, Akihiro; Suzuki, Yuka; Yoshikawa, Jyunpei; Kato-Sato, Akiko; Furukawa, Shin; Nishio, Taro; Kitakawa, Hirohiko; Miya, Aika; Kameda, Hiraku; Nakazawa, Daigo; Nakamura, Akinobu; Sakai, Kiyoshi; Atsumi, Tatsuya","year":2025,"journal":"Therapeutic advances in endocrinology and metabolism, 16, 20420188251378216","doi":"10.1177/20420188251378216","pmid":"40979838","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12843","title":"Glucagon-like Peptide-1 Receptor Agonists: A New Frontier in Treating Alcohol Use Disorder.","authors":"Oesterle, Tyler S; Ho, Ming-Fen","year":2025,"journal":"Brain sciences, 15(7)","doi":"10.3390/brainsci15070702","pmid":"40722294","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12844","title":"GLP-1 receptor agonists in atherosclerotic cardiovascular disease and diabetes mellitus or obesity: investigation of the potential role in a German inpatient dataset.","authors":"Oettinger, Vera; von Zur Mühlen, Constantin; Kaier, Klaus; Wolf, Dennis; Rilinger, Jonathan; Maier, Alexander; Jäckel, Markus; Westermann, Dirk; Hilgendorf, Ingo; Bockelmann, Dalibor","year":2025,"journal":"Clinical research in cardiology : official journal of the German Cardiac Society","doi":"10.1007/s00392-025-02735-z","pmid":"40839017","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12845","title":"Deep Learning for Cardiac Overload Estimation　- Predicting B-Type Natriuretic Peptide (BNP) Levels From Heart Sounds and Electrocardiogram.","authors":"Ogawa, Shimpei; Ishii, Masanobu; Saito, Shumpei; Seki, Hiroshi; Ikeda, Koshiro; Yasui, Yuhei; Komatsu, Tomohiro; Sato, Ginga; Tabata, Noriaki; Ohishi, Mitsuru; Kubozono, Takuro; Saito, Naritatsu; Kato, Eri Toda; Song, Xiaoyang; Yamada, Masahiro; Natori, Shunsuke; Kunikane, Yuki; Yokomatsu, Takafumi; Kato, Masashi; Sagara, Yasuaki; Uchiyama, Nami; Atsuchi, Nobuhiko; Kawahara, Shota; Natsugoe, Shoji; Tsujita, Kenichi","year":2025,"journal":"Circulation journal : official journal of the Japanese Circulation Society, 89(10), 1684-1692","doi":"10.1253/circj.CJ-25-0098","pmid":"40533163","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12846","title":"Use of glucagon-like peptide-1 receptor agonists in idiopathic intracranial hypertension : a systematic review.","authors":"Ognard, Julien; Alipour Khabir, Sevda; Ghozy, Sherief; El Hajj, Gerard; Kallmes, Kevin M; Chen, John J; Kadirvel, Ramanathan; Kallmes, David F; Brinjikji, Waleed","year":2025,"journal":"The journal of headache and pain, 26(1), 202","doi":"10.1186/s10194-025-02148-3","pmid":"41057780","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12847","title":"Are We Ready to Measure Skin Permeation of Modern Antiaging GHK-Cu Tripeptide Encapsulated in Liposomes?","authors":"Ogórek, Karolina; Nowak, Kinga; Wadych, Emilia; Ruzik, Lena; Timerbaev, Andrei R; Matczuk, Magdalena","year":2025,"journal":"Molecules (Basel, Switzerland), 30(1)","doi":"10.3390/molecules30010136","pmid":"39795193","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review found that:\n\n- GHK-Cu is a hydrophilic (water-loving) tripeptide with limited ability to cross the lipophilic (fat-loving) stratum corneum skin barrier\n- Liposomes are theoretically capable of improving GHK-Cu skin penetration by encapsulating it in a lipid-compatible carrier\n- Methods exist for studying skin permeation of cosmetically active compounds, including Franz diffusion cells and various analytical detection techniques\n- However, the transport of liposome-encapsulated GHK-Cu through skin has received very little scientific attention\n- This represents a significant research gap between the widespread commercial use of GHK-Cu in skincare products and the actual evidence for its skin penetration effectiveness","whyItMatters":"GHK-Cu is one of the most popular peptide ingredients in the multi-billion dollar anti-aging skincare market. Products containing this peptide are marketed with bold claims about skin rejuvenation, yet this review reveals that fundamental questions about whether the peptide even reaches the skin layers where it needs to work remain largely unanswered. This gap between marketing and science has implications for consumers, regulators, and product developers. Addressing it could either validate GHK-Cu's effectiveness or reveal that better delivery methods are needed.","specificNumbers":"","methodology":"The authors conducted a literature review examining methods for studying the transport of cosmetically active compounds (both free and liposome-encapsulated) across the skin barrier. They assessed available techniques for measuring skin permeation, analyzed existing data on free GHK-Cu skin penetration, and specifically searched for studies on liposome-encapsulated GHK-Cu transport.","limitations":"As a review highlighting a research gap, the paper primarily identifies what is missing rather than providing new data. The authors do not present original permeation experiments. The discussion of liposome-based delivery is theoretical rather than based on demonstrated GHK-Cu permeation improvements. The review focuses on methodological readiness rather than biological efficacy — even if permeation were demonstrated, whether sufficient GHK-Cu reaches target skin cells to produce meaningful anti-aging effects is a separate question."},{"rthcId":"RPEP-12848","title":"Spider Venom-Derived Peptide Exhibits Dual Anti-Inflammatory and Antioxidative Activities in LPS-Stimulated BEAS-2B Cells.","authors":"Oh, Jin Wook; Shin, Min Kyoung; Park, Hye-Ran; Jeong, Sukin; Lee, Minho; Ko, Ji Hyuk; Lee, Jae Young; Jee, Seung-Cheol; Sung, Jung-Suk","year":2025,"journal":"Antioxidants (Basel, Switzerland), 14(12)","doi":"10.3390/antiox14121485","pmid":"41462684","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"NC-CV, a peptide designed from Nephila clavata venom gland transcriptome using in silico analysis and machine learning functional prediction, demonstrated dual activities in LPS-stimulated human bronchial epithelial (BEAS-2B) cells: it reduced pro-inflammatory cytokine expression and decreased intracellular reactive oxygen species (ROS) generation while improving cell viability.\n\nMechanistically, NC-CV blocks TLR4 signaling activation (confirmed by molecular docking simulations), suppressing downstream NF-κB and MAPK inflammatory pathways. Its antioxidant activity was primarily through direct ROS scavenging rather than inducing endogenous antioxidant enzymes. This dual mechanism disrupts the self-reinforcing cycle of inflammation and oxidative stress in airway epithelium.","whyItMatters":"Respiratory diseases like asthma, COPD, and acute lung injury involve both inflammation and oxidative damage that feed each other in a destructive cycle. Most current treatments address only one of these problems. A single peptide that tackles both simultaneously — by blocking the inflammatory trigger (TLR4) and directly scavenging the oxidative damage — could provide more effective treatment than existing approaches.","specificNumbers":"","methodology":"Peptide discovery: Nephila clavata venom gland transcriptome was mined using in silico analysis and machine learning to identify candidates with predicted anti-inflammatory and antioxidant properties and low cytotoxicity. Experimental validation: NC-CV was tested on LPS-stimulated BEAS-2B human bronchial epithelial cells for viability, cytokine expression, and ROS levels. Mechanism was investigated via pathway analysis (NF-κB, MAPK) and molecular docking simulations targeting TLR4.","limitations":"This is an in vitro study using a single human bronchial cell line (BEAS-2B) with LPS stimulation, which doesn't capture the full complexity of respiratory disease in living organisms. The peptide has not been tested in animal models for efficacy, toxicity, or pharmacokinetics. Molecular docking simulations suggest but do not prove TLR4 as the primary target. Stability, delivery route, and formulation for respiratory applications have not been addressed."},{"rthcId":"RPEP-12849","title":"Effect of glucagon-like peptide-1 receptor agonists on gastric mucosal visibility during upper endoscopy in Asian patients with diabetes.","authors":"Oh, Young Eun; Kim, Tae-Se; Chi, Sang Ah; Park, Hyun Jung; Min, Yang Won; Lee, Hyuk; Lee, Jun Haeng; Rhee, Poong-Lyul; Kim, Jae J; Min, Byung-Hoon","year":2025,"journal":"World journal of diabetes, 16(12), 112694","doi":"10.4239/wjd.v16.i12.112694","pmid":"41480609","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12850","title":"Effects of switching from dipeptidyl peptidase 4 inhibitors to oral semaglutide on oxidative stress and glycemic variability in patients with type 2 diabetes: an open-label, prospective, randomized, multicenter, parallel-group comparison study.","authors":"Ohara, Makoto; Yokoyama, Hiroki; Seino, Hiroaki; Fujikawa, Tomoki; Kohata, Yo; Takahashi, Noriyuki; Irie, Shunichiro; Terasaki, Michishige; Mori, Yusaku; Fukui, Tomoyasu; Yamagishi, Sho-Ichi","year":2025,"journal":"Diabetology & metabolic syndrome, 17(1), 126","doi":"10.1186/s13098-025-01691-y","pmid":"40229852","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Switching from DPP-4 inhibitors to oral semaglutide for 24 weeks significantly reduced oxidative stress (measured by the diacron-reactive oxygen metabolites test), improved glucose variability as measured by continuous glucose monitoring, and lowered HbA1c levels compared to continuing DPP-4 inhibitor therapy.\n\nImportantly, while the metabolic and biochemical markers improved significantly, patient-reported treatment satisfaction scores did not differ between groups, indicating the benefits were measurable but didn't translate to a perceived difference in quality of life over this time period.","whyItMatters":"As GLP-1 receptor agonists like semaglutide become increasingly available in oral form, clinicians need evidence to guide decisions about switching patients from older diabetes medications. This study provides direct comparative data showing that the switch offers measurable metabolic benefits beyond just blood sugar control — including reduced oxidative stress, which is linked to long-term cardiovascular complications.","specificNumbers":"","methodology":"This was an open-label, prospective, randomized, multicenter, parallel-group study over 24 weeks. 58 patients with type 2 diabetes who had been on DPP-4 inhibitors for at least 12 weeks were randomized to either continue their DPP-4 inhibitor (n=28) or switch to oral semaglutide starting at 3 mg/day, increased to 7 mg/day after 4 weeks (n=30). Glucose variability was measured using continuous glucose monitoring. Final analysis included 51 patients (24 semaglutide, 27 DPP-4).","limitations":"The open-label design means neither patients nor doctors were blinded to treatment assignment, which could introduce bias. The sample size was small (58 enrolled, 51 analyzed), and 7 patients dropped out — 6 from the semaglutide group. The 24-week duration may not capture long-term outcomes. The study did not report specific effect sizes for oxidative stress or glucose variability in the abstract."},{"rthcId":"RPEP-12851","title":"Correlations between amyloid-β peptide levels in aqueous humor and retinal thickness in patients with glaucoma.","authors":"Ohashi, Tsutomu; Harada, Takayuki; Namekata, Kazuhiko; Shinmei, Yasuhiro; Fujiya, Akio; Yoshida, Maiko; Kojima, Takashi","year":2025,"journal":"Scientific reports, 15(1), 45143","doi":"10.1038/s41598-025-33346-3","pmid":"41430362","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12852","title":"Atrial Natriuretic Peptide at Discharge as a Predictive Marker for Early Rehospitalization in Patients With Heart Failure With Preserved Ejection Fraction.","authors":"Ohno, Junichi; Min, Kyung-Duk; Sunayama, Isamu; Matsumoto, Yuki; Daimon, Aika; Manabe, Eri; Oboshi, Makiko; Azuma, Kohei; Sugahara, Masataka; Eguchi, Akiyo; Naito, Yoshiro; Asakura, Masanori; Ishihara, Masaharu","year":2025,"journal":"Journal of the American Heart Association, 14(16), e040320","doi":"10.1161/JAHA.124.040320","pmid":"40792585","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12853","title":"Prognostic Value of B-Type Natriuretic Peptide Level in Patients With Heart Failure With a Higher Left Ventricular Ejection Fraction.","authors":"Ohte, Nobuyuki; Kikuchi, Shohei; Iwahashi, Noriaki; Kinugasa, Yoshiharu; Dohi, Kaoru; Takase, Hiroyuki; Inoue, Katsuji; Okumura, Takahiro; Hachiya, Kenta; Sugiura, Emiyo; Kusunose, Kenya; Kitada, Shuichi; Seo, Yoshihiro","year":2025,"journal":"Circulation reports, 7(3), 191-197","doi":"10.1253/circrep.CR-24-0172","pmid":"40066216","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 231 patients with heart failure and LVEF >40% (spanning HFmrEF and HFpEF categories), BNP levels were measured at hospital discharge:\n\n- BNP levels were NOT significantly different across the three LVEF groups: HFmrEF median 195 pg/mL, HFpEF (LVEF 50-59%) median 242 pg/mL, and HFpEF (LVEF ≥60%) median 220 pg/mL (P=0.422)\n- Despite similar BNP levels across groups, a BNP cutoff of ≥377 pg/mL significantly differentiated event-free survival (P<0.001)\n- In multivariate Cox regression, BNP was independently associated with event-free survival after adjusting for LVEF, E/e' (a measure of heart stiffness), and concurrent atrial fibrillation\n\nThis means BNP provides prognostic information beyond what other standard heart failure measurements offer.","whyItMatters":"Heart failure with preserved ejection fraction (HFpEF) accounts for roughly half of all heart failure cases and is notoriously difficult to manage because the standard measure — how much blood the heart pumps per beat — looks relatively normal. This study confirms that BNP, a simple blood test, can identify which HFpEF patients are at highest risk for death or rehospitalization, even when other measurements look similar. This could help doctors make better treatment and follow-up decisions.","specificNumbers":"","methodology":"This was a multicenter, prospective, observational cohort study. Patients with heart failure and LVEF >40% at hospital discharge (n=231) had BNP levels, LVEF, E/e' (diastolic function marker), and atrial fibrillation status recorded. The composite endpoint was all-cause death and readmission due to heart failure. A BNP cutoff of 377 pg/mL was used for survival analysis. Multi-covariate Cox proportional hazards modeling assessed BNP's independent prognostic value after adjusting for LVEF, E/e', and atrial fibrillation.","limitations":"The sample size of 231 is moderate for a prognostic study. The BNP cutoff of 377 pg/mL may not be generalizable to all populations — BNP levels are affected by age, sex, obesity, kidney function, and other factors. The study enrolled only patients with LVEF >40%, so findings do not apply to patients with severely reduced ejection fraction. BNP was measured once at discharge; serial measurements might provide additional prognostic value. The observational design cannot establish causation between BNP levels and outcomes."},{"rthcId":"RPEP-12854","title":"Oligopeptides and Polypeptides Impact Norepinephrine Detection in Lymphoid Tissue.","authors":"Ojha, Sarbeshwar; Brooke, Alexandra K; Ostertag, Blaise J; Murrow, Daniel P; Witt, Colby E; Ross, Ashley E","year":2025,"journal":"ACS chemical neuroscience, 16(19), 3851-3860","doi":"10.1021/acschemneuro.5c00554","pmid":"40935127","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12855","title":"The Different Cellular Entry Routes for Drug Delivery Using Cell Penetrating Peptides.","authors":"Okafor, Michael; Schmitt, David; Ory, Stéphane; Gasman, Stéphane; Hureau, Christelle; Faller, Peter; Vitale, Nicolas","year":2025,"journal":"Biology of the cell, 117(6), e70012","doi":"10.1111/boc.70012","pmid":"40490965","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12856","title":"Effects of Near-Infrared Diode Laser Irradiation on Pain Relief and Neuropeptide Markers During Experimental Tooth Movement in the Periodontal Ligament Tissues of Rats: A Pilot Study.","authors":"Okazaki, Kanako; Nakatani, Ayaka; Kunimatsu, Ryo; Kado, Isamu; Sakata, Shuzo; Kiridoshi, Hirotaka; Tanimoto, Kotaro","year":2025,"journal":"International journal of molecular sciences, 26(15)","doi":"10.3390/ijms26157404","pmid":"40806533","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12857","title":"Relative Impact of GLP-1 Agonist Use on Microvascular Versus Macrovascular Complications.","authors":"Okorigba, Efeturi M; Jinadu, Kehinde H; Utuk, Oto-Obong J; Akinwumiju, Akinyemi; Kolawole, Olasunkanmi A; Disu, Fatimot; Sosu, Victor","year":2025,"journal":"Cureus, 17(10), e93925","doi":"10.7759/cureus.93925","pmid":"41147020","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12858","title":"Phosphoproteomic analysis of signal transduction dynamics induced by a modified cell-penetrating peptide-protein complex.","authors":"Okuda, Akiko; Takihara, Hayato; Kuroiwa, Reika; Okuda, Shujiro","year":2025,"journal":"Biochemical and biophysical research communications, 778, 152356","doi":"10.1016/j.bbrc.2025.152356","pmid":"40700806","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12859","title":"Effects of Tirzepatide on Patients With Type 2 Diabetes and Metabolic Dysfunction-Associated Steatotic Liver Disease: A Retrospective Cohort Study.","authors":"Okuma, Hideyuki","year":2025,"journal":"Cureus, 17(5), e83712","doi":"10.7759/cureus.83712","pmid":"40486301","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12860","title":"Epigenetic modification of hypothalamic neuropeptides and metabolic hormone receptors in metabolic health.","authors":"Oladun, Busayo; Mall, Smita; Kim, Min-Hyun","year":2025,"journal":"Frontiers in endocrinology, 16, 1645474","doi":"10.3389/fendo.2025.1645474","pmid":"41040868","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12861","title":"The Effects of Glucagon-Like Peptide-1 Receptor Agonists on Mitochondrial Function Within Skeletal Muscle: A Systematic Review.","authors":"Old, Victoria J; Davies, Melanie J; Papamargaritis, Dimitris; Choudhary, Pratik; Watson, Emma L","year":2025,"journal":"Journal of cachexia, sarcopenia and muscle, 16(1), e13677","doi":"10.1002/jcsm.13677","pmid":"39815782","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12862","title":"Myofascial trigger points therapy increases neck mobility and reduces headache pain in migraine patients - pilot study.","authors":"Olesiejuk, Maciej; Chalimoniuk, Małgorzata; Sacewicz, Tomasz","year":2025,"journal":"BMC musculoskeletal disorders, 26(1), 105","doi":"10.1186/s12891-025-08360-1","pmid":"39893364","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12863","title":"Acute GLP-1 Agonism Induces Arrhythmogenic Electrical Activity in Aged Mice Heart Through Impaired Cellular Na+ and Ca2+ Handlings: The Role of CK2 Hyperphosphorylation.","authors":"Olgar, Yusuf; Durak, Ayşegül; Turan, Belma","year":2025,"journal":"Anatolian journal of cardiology, 29(2), 83-94","doi":"10.14744/AnatolJCardiol.2024.4719","pmid":"39655941","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12864","title":"Isolation and partial characterization of antimicrobial peptide-enriched fractions from Parabacteroides distasonis.","authors":"Oliveira, Anna Gabriella Guimarães; Haq, Ihtisham Ul; de Oliveira, Patrícia Luciana; de Oliveira, Jamil Silvano; Bemquerer, Marcelo Porto; Magalhães, Paula Prazeres; de Macêdo Farias, Luiz","year":2025,"journal":"Scientific reports, 15(1), 43043","doi":"10.1038/s41598-025-26614-9","pmid":"41330952","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12865","title":"A Pharmacological Dose of Liraglutide Improves Mitochondrial Performance in Mouse Leydig Cells.","authors":"Oliveira-Lopes, Bruno; Braga, Patrícia C; Oliveira, Pedro F; Alves, Marco G; Bernardino, Raquel L","year":2025,"journal":"International journal of molecular sciences, 26(18)","doi":"10.3390/ijms26188903","pmid":"41009468","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Liraglutide at pharmacological concentrations increased the metabolic viability of mouse Leydig cells and reduced reactive oxygen species (ROS) production at all concentrations tested. Mitochondrial performance was significantly enhanced: increased basal respiration, maximal respiration, proton leak, and ATP-linked oxygen consumption rate. Mitochondrial membrane potential and mtDNA copy number were also assessed. Androstenedione (testosterone precursor) production was unchanged, likely due to inherent limitations of the BLTK1 cell line in supporting full steroidogenesis.","whyItMatters":"Obesity and type 2 diabetes are strongly associated with low testosterone and male infertility. As GLP-1 receptor agonists become the dominant treatment for these conditions, understanding their effects on reproductive cells is crucial. This study provides the first evidence that liraglutide directly benefits Leydig cell mitochondrial function, potentially explaining clinical observations of improved testosterone levels in men taking GLP-1 drugs for weight loss.","specificNumbers":"Increased metabolic viability · Reduced ROS at all concentrations · Enhanced basal respiration, maximal respiration, proton leak, ATP-linked OCR · Androstenedione production unchanged","methodology":"In vitro study using the BLTK1 mouse Leydig cell line. Cells were cultured with or without liraglutide at pharmacological and supra-pharmacological concentrations. Assessed: metabolic viability, cell proliferation, LDH release (cytotoxicity), ROS production, mitochondrial membrane potential, real-time mitochondrial respiration (Seahorse-style analysis), mtDNA copy number, and androstenedione production.","limitations":"This is an in vitro study using an immortalized mouse cell line (BLTK1), which may not fully represent primary Leydig cells or human testicular physiology. The lack of change in androstenedione production may reflect cell line limitations rather than a true null effect on steroidogenesis. No in vivo validation was performed. The concentrations used may not perfectly reflect what Leydig cells encounter in the testis during systemic liraglutide treatment."},{"rthcId":"RPEP-12866","title":"Sex differences in intestinal morphology and increase in diencephalic neuropeptide Y gene expression in female but not male Pekin ducks exposed to chronic heat stress.","authors":"Oluwagbenga, E M; Bergman, M; Ajuwon, K M; Fraley, G S","year":2025,"journal":"Journal of neuroendocrinology, 37(6), e13424","doi":"10.1111/jne.13424","pmid":"38960698","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12867","title":"Differences in the management of heart failure with preserved ejection fraction among physicians from Europe, the Middle East and North Africa: an international survey.","authors":"Omer, Mohamed H; Shchendrygina, Anastasia; Ahmad, Omar; Saldarriaga, Clara; Goldfeder de Gracia, Sydney; Alhussain, Mosaad; Echahidi, Najmeddine; Kharabsheh, Suleiman M; Ayoubi, Fakhr; Alghalayni, Kamal; Alburaiki, Jehad; Fadel, Bahaa; Bader, Feras; Skouri, Hadi; Hamade, Mohamad; Załęska-Kocięcka, Marta; Guidetti, Federica; Mewton, Nathan; Mohty, Dania","year":2025,"journal":"Open heart, 12(2)","doi":"10.1136/openhrt-2025-003548","pmid":"40819913","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12868","title":"Sacubitril/Valsartan and Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy: The PRADA II Randomized Clinical Trial.","authors":"Omland, Torbjørn; Heck, Siri Lagethon; Holte, Espen; Lilleaasen, Albulena Mecinaj; Gynnild, Mari Nordbø; Fagerland, Morten Wang; Vinje-Jakobsen, Victoria; Næs, Anne-Katrine Lislegaard; Blix, Egil Støre; Larsen, Alf Inge; Geisler, Jürgen; Gulati, Geeta; Wethal, Torgeir","year":2025,"journal":"Circulation, 152(16), 1136-1145","doi":"10.1161/CIRCULATIONAHA.125.076616","pmid":"40884047","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12869","title":"From Control to Cure: Insights into the Synergy of Glycemic and Antibiotic Management in Modulating the Severity and Outcomes of Diabetic Foot Ulcers.","authors":"Omotosho, Idris Ajibola; Shamsuddin, Noorasyikin; Zaman Huri, Hasniza; Chong, Wei Lim; Rehman, Inayat Ur","year":2025,"journal":"International journal of molecular sciences, 26(14)","doi":"10.3390/ijms26146909","pmid":"40725154","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies multiple mechanisms by which GLP-1 receptor agonists and DPP-4 inhibitors improve diabetic foot ulcer outcomes:\n\n- Reduce AGE formation and AGE-RAGE-NF-κB inflammatory signaling caused by chronic hyperglycemia\n- Promote macrophage polarization from pro-inflammatory M1 to reparative M2 phenotype\n- Enhance angiogenesis, inflammation resolution, and tissue regeneration through AMPK, mTOR, and VEGF signaling\n- Glycemic stability (via CGM and antihyperglycemic adherence) improves immune cell function and reduces bacterial virulence, enhancing antibiotic effectiveness\n- An integrated approach addressing both metabolic and microbial factors is advocated to restore wound homeostasis and reduce amputation risk","whyItMatters":"Diabetic foot ulcers remain a leading cause of non-traumatic amputations worldwide. While antibiotics and wound care are standard treatments, this review highlights that the type of diabetes drug used matters — GLP-1 drugs may actively promote healing beyond just controlling blood sugar. This could change how clinicians approach diabetic wound management, prioritizing drugs with wound-healing benefits.","specificNumbers":"","methodology":"This is a narrative review consolidating molecular evidence on the combined effects of glycemic control (using metformin, GLP-1 RAs, and DPP-4 inhibitors) and antibiotic therapies in diabetic foot ulcers. The review examines molecular pathways, immune mechanisms, and clinical evidence for integrated metabolic-antimicrobial management.","limitations":"As a narrative review, this does not present original data or conduct a systematic search. Much of the evidence for GLP-1 effects on wound healing comes from preclinical studies, with limited clinical trial data specifically in diabetic foot ulcers. The molecular pathways described are largely based on in vitro and animal studies. Controlled clinical trials specifically testing GLP-1 drugs for diabetic foot ulcer outcomes are needed."},{"rthcId":"RPEP-12870","title":"Novel Circulating Biomarkers in Aortic Valve Stenosis.","authors":"Ong, Joy Yi-Shan; Tan, Sarah Ming Li; Koh, Angela S; Kong, William; Sia, Ching Hui; Yeo, Tiong Cheng; Quek, Swee Chye; Poh, Kian Keong","year":2025,"journal":"International journal of molecular sciences, 26(5)","doi":"10.3390/ijms26051902","pmid":"40076529","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12871","title":"Can serum neuropeptide levels help diagnose pediatric migraine? A prospective case-control study.","authors":"Orak, Sibğatullah Ali; Polat, Muzaffer; Pak, Mert; Çerçi Kubur, Çisil; Atasever, Aslı Kübra; Yilmaz, Celil; Taneli, Fatma; Angin, Ahmet; Cengiz Özyurt, Beyhan","year":2025,"journal":"Headache, 65(10), 1821-1830","doi":"10.1111/head.14981","pmid":"40454710","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12872","title":"Is liraglutide safe and effective in the elderly obese patients?: A single center experience.","authors":"Oral, Alihan; Küçük, Celalettin; Kayalar, Yunus","year":2025,"journal":"Medicine, 104(16), e42155","doi":"10.1097/MD.0000000000042155","pmid":"40258760","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12873","title":"GLP-1 Receptor Agonist Outcomes, Safety, and Body Mass Index Change in a National Cohort of Patients on Dialysis.","authors":"Orandi, Babak J; Chen, Yusi; Li, Yiting; Charytan, David; Lentine, Krista L; Lee, Brian P; Ali, Nicole; DeMarco, Mario P; Weintraub, Michael A; Bae, Sunjae; Lonze, Bonnie E; Ren-Fielding, Christine J; Lofton, Holly; Gujral, Akash; Segev, Dorry L; McAdams-DeMarco, Mara","year":2025,"journal":"Clinical journal of the American Society of Nephrology : CJASN, 20(8), 1100-1110","doi":"10.2215/CJN.0000000750","pmid":"40526425","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12874","title":"Associations Between Common Hip and Knee Osteoarthritis Treatments and All-Cause Mortality.","authors":"Orchard, John W; Tutt, L Edward; Hines, Anna; Orchard, Jessica J","year":2025,"journal":"Healthcare (Basel, Switzerland), 13(17)","doi":"10.3390/healthcare13172229","pmid":"40941581","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12875","title":"Effectiveness of transcranial direct current stimulation and monoclonal antibodies acting on the CGRP as a combined treatment for migraine (TACTIC): Results of a randomized controlled trial.","authors":"Ornello, Raffaele; D'Atri, Aurora; De Icco, Roberto; De Santis, Federico; Rosignoli, Chiara; Onofri, Agnese; Vaghi, Gloria; Cammarota, Francescantonio; Brancaccio, Carla; Corrado, Michele; Bighiani, Federico; Grillo, Valentina; Sances, Grazia; Corigliano, Domenico; Salfi, Federico; Tassorelli, Cristina; Ferrara, Michele; Sacco, Simona","year":2025,"journal":"Cephalalgia : an international journal of headache, 45(5), 3331024251325567","doi":"10.1177/03331024251325567","pmid":"40384614","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Active tDCS significantly reduced migraine days compared to sham during the 28-day follow-up (p = 0.008, large effect size ηp² = 0.241). The active group showed a within-group reduction from baseline (Cohen's d = 0.660, p = 0.023), while the sham group did not. However, total headache days did not differ significantly between groups (p = 0.560). Neurophysiologically, active tDCS decreased delta power at frontal brain regions compared to sham, suggesting modulation of central mechanisms.","whyItMatters":"CGRP-targeting drugs are highly effective for migraine prevention, but a significant proportion of patients retain a substantial migraine burden. This trial demonstrates that combining CGRP antibodies (targeting peripheral peptide pathways) with brain stimulation (targeting central mechanisms) can provide additional relief, supporting a multi-modal approach to migraine management that addresses different parts of the disease pathway.","specificNumbers":"","methodology":"Multicenter, randomized, double-blind, sham-controlled, parallel-group trial (NCT05161871). 30 migraine patients on CGRP monoclonal antibodies for ≥90 days with ≥8 monthly migraine days were randomized to active or sham tDCS (15 per group). The protocol consisted of five daily 20-minute sessions with bilateral cathodal stimulation on the occipital area and anodal stimulation on M1. High-density EEG was recorded before and after treatment. Primary endpoint: headache days during 28-day follow-up. Analysis of covariance compared groups.","limitations":"The sample size is very small (n=30, 15 per group), limiting statistical power and generalizability. The distinction between significant reduction in migraine days but not headache days is puzzling and may reflect the small sample. The 28-day follow-up is short, and durability of the combined effect is unknown. The tDCS protocol was brief (5 sessions), and longer courses might show different results."},{"rthcId":"RPEP-12876","title":"Impact of duration of chronic migraine on long-term effectiveness of monoclonal antibodies targeting the calcitonin gene-related peptide pathway-A real-world study.","authors":"Ornello, Raffaele; Baldini, Francesca; Onofri, Agnese; Rosignoli, Chiara; De Santis, Federico; Burgalassi, Andrea; Chiarugi, Alberto; Geppetti, Pierangelo; Sacco, Simona; Iannone, Luigi Francesco","year":2025,"journal":"Headache, 65(1), 61-67","doi":"10.1111/head.14788","pmid":"39012070","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12877","title":"GLP-1 Signalling as a Therapeutic Avenue in Parkinson's Disease: A Comprehensive Review.","authors":"Orozco, María Paz; Vintimilla Rivadeneira, Valentina; Leon-Rojas, Jose E","year":2025,"journal":"International journal of molecular sciences, 26(24)","doi":"10.3390/ijms262412163","pmid":"41465588","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review consolidates evidence showing GLP-1 receptor agonists activate multiple neuroprotective signaling pathways relevant to Parkinson's disease: PI3K/Akt, MAPK/ERK, cAMP/PKA-CREB, and AMPK. These pathways converge on four key neuroprotective mechanisms — mitochondrial homeostasis, proteostasis (clearing toxic protein aggregates like alpha-synuclein), neuroinflammation reduction, and synaptic resilience.\n\nPreclinical studies across multiple Parkinson's disease models demonstrate neuroprotective effects for exendin-4, liraglutide, semaglutide, lixisenatide, and emerging dual agonists. However, clinical translation has been complicated by differences in blood-brain barrier penetration and pharmacokinetics between agents. The review identifies these pharmacological factors as likely explanations for divergent clinical trial outcomes.","whyItMatters":"Parkinson's disease affects over 10 million people worldwide and has no disease-modifying treatment. The connection between type 2 diabetes and increased Parkinson's risk has sparked interest in repurposing diabetes drugs — particularly GLP-1 receptor agonists — for neuroprotection. If these widely available, well-characterized drugs prove effective for slowing Parkinson's, it would represent one of the most impactful drug repurposing successes in medicine.","specificNumbers":"","methodology":"This is a comprehensive narrative review integrating evidence from three domains: biochemical analysis of GLP-1 signaling pathways, preclinical studies across major Parkinson's disease animal models, and clinical trial data. The review compares key GLP-1 agonists for therapeutic potential, evaluates dose comparability and blood-brain barrier penetration, and identifies factors that may explain differing clinical outcomes.","limitations":"As a review, this paper synthesizes existing evidence but doesn't present new data. The preclinical evidence, while promising, comes from animal models that imperfectly replicate human Parkinson's disease. Clinical trial results have been mixed, and the review acknowledges that blood-brain barrier penetration, dose comparability, and trial design differences may explain inconsistent human results. The optimal GLP-1RA, dose, and timing for neuroprotection in Parkinson's remain undefined."},{"rthcId":"RPEP-12878","title":"Effect of GLP-1 agonists on testosterone levels: a systematic review and meta-analysis.","authors":"Orra, Soraya Hussein; Martinez, Juan Victor Nabhan; Porto, Breno Cordeiro; Passerotti, Carlo Camargo; Sardenberg, Rodrigo A S; Da Cruz, Jose Arnaldo Shiomi","year":2025,"journal":"BMC urology, 25(1), 311","doi":"10.1186/s12894-025-02005-0","pmid":"41291666","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12879","title":"Gastrointestinal stability and DPP-IV inhibitory activity of tilapia (Oreochromis niloticus) viscera hydrolysate-derived novel peptides LPCL and TPFLPDE, with LPCL-modulated GLP-1 and PepT1 expression in STC-1 cells.","authors":"Ortizo, Rhessa Grace Guanga; Lai, Ching-Shu; Anwar, Choirul; Sharma, Vishal; Sun, Pei-Pei; Chen, Chiu-Wen; Dong, Cheng-Di; Tsai, Mei-Ling","year":2025,"journal":"Food research international (Ottawa, Ont.), 219, 116986","doi":"10.1016/j.foodres.2025.116986","pmid":"40922149","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12880","title":"Effect of Galcanezumab on PHQ-9 and GAD-7 in Patients with Migraine: A Real-world Study in Japan.","authors":"Oshima, Kota; Hattori, Yuna; Ihara, Keiko; Watanabe, Narumi; Takemura, Ryo; Ishizuchi, Kei; Takahashi, Nobuyuki; Sekiguchi, Koji; Nakahara, Jin; Takizawa, Tsubasa","year":2025,"journal":"Internal medicine (Tokyo, Japan)","doi":"10.2169/internalmedicine.5856-25","pmid":"40803856","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Monthly migraine days decreased significantly from 13.6 to 8.5 (p<0.001) during galcanezumab treatment. Depression scores (PHQ-9) dropped from 5.8 to 4.5 (p=0.010) and anxiety scores (GAD-7) from 4.0 to 3.1 (p=0.030).\n\nCritically, no significant correlation was found between changes in depression/anxiety scores and changes in monthly migraine days, pain severity (NRS), or associated migraine symptoms. Fisher's exact tests also showed no significant association between PHQ-9/GAD-7 improvements and migraine frequency reduction. This suggests galcanezumab may have direct mood-modulating effects independent of its migraine-reducing action.","whyItMatters":"Depression and anxiety significantly worsen quality of life for migraine sufferers, yet they are often treated as separate conditions. If CGRP-blocking peptide therapies directly improve mental health — not just as a side effect of fewer headaches — it would fundamentally change how clinicians think about these drugs. CGRP may play a broader role in mood regulation than previously recognized.","specificNumbers":"","methodology":"Single-center, retrospective, real-world study at Keio University Hospital in Japan. 27 migraine patients treated with galcanezumab were assessed using validated depression (PHQ-9) and anxiety (GAD-7) questionnaires at baseline and 3-5 months after starting treatment. Correlation analyses examined whether mood improvements were linked to migraine improvement metrics.","limitations":"Very small sample size (27 patients) limits statistical power and generalizability. The retrospective, single-center design without a control group means improvements could reflect placebo effects, natural fluctuation, or other factors. The 3-5 month follow-up is relatively short. Baseline depression and anxiety scores were relatively mild (below clinical thresholds for disorder), so the clinical significance of the improvements is debatable. The study was conducted only in Japanese patients, limiting cross-population generalizability."},{"rthcId":"RPEP-12881","title":"Efficacy and Safety of Switching between Anti-CGRP Monoclonal Antibodies: A Detailed Monthly and Long-term Follow-up Study and Literature Review.","authors":"Oshima, Kota; Ihara, Keiko; Watanabe, Narumi; Takemura, Ryo; Ishizuchi, Kei; Takahashi, Nobuyuki; Shibata, Mamoru; Nakahara, Jin; Takizawa, Tsubasa","year":2025,"journal":"Internal medicine (Tokyo, Japan), 64(14), 2114-2123","doi":"10.2169/internalmedicine.4360-24","pmid":"39756881","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12882","title":"Paving the way for new antimicrobial peptides through molecular de-extinction.","authors":"Osiro, Karen O; Gil-Ley, Abel; Fernandes, Fabiano C; de Oliveira, Kamila B S; de la Fuente-Nunez, Cesar; Franco, Octavio L","year":2025,"journal":"Microbial cell (Graz, Austria), 12, 1-8","doi":"10.15698/mic2025.02.841","pmid":"40012704","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12883","title":"The Role of Epicardial Fat Thickness and B-type Natriuretic Peptide (BNP)/N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) in Heart Failure Risk Stratification: A Systematic Review.","authors":"Osman Mohamed, Areij Awad; Bashir Omer, Sahla Shurahbeel; Mukhtar, Musab; Mohmmed, Tagwa; Hussein Mohamed, Wadah Mohamed; Mohamed Hassan, Miska Haroun; Mohammed Hassan, Ibrahim","year":2025,"journal":"Cureus, 17(5), e84184","doi":"10.7759/cureus.84184","pmid":"40525067","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12884","title":"Echoes of Dormancy: Anomic Aphasia Unveils Neurocysticercosis Reactivation in a Patient on Semaglutide.","authors":"Osorio Borjas, Marcos; Hernandez, Robert J; Lopez-Lacayo, Angelo; Laffita Perez, Dalina; Oliva, Yanie; Mercado, Julio; Hussain, Hussain","year":2025,"journal":"NeuroSci, 6(2)","doi":"10.3390/neurosci6020040","pmid":"40407613","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A patient on semaglutide developed anomic aphasia (difficulty naming objects) — a rare neurological manifestation — from reactivation of neurocysticercosis cysts that had been dormant for decades. Brain imaging confirmed localized cystic changes. The proposed mechanism is that semaglutide attenuated the protective inflammatory response maintained by astrocytes and microglia around the dormant cysts, allowing reactivation. Treatment with antiparasitic agents and corticosteroids led to marked clinical improvement.","whyItMatters":"As semaglutide and other GLP-1 drugs are prescribed to millions of people worldwide — including in regions where parasitic infections like neurocysticercosis are endemic — this case raises a novel safety signal. GLP-1 receptor agonists have well-documented anti-inflammatory effects in the brain, which are being explored as benefits for Alzheimer's and other neurological conditions. But this case suggests those same anti-inflammatory effects could be a risk in patients harboring dormant infections kept in check by chronic inflammation.","specificNumbers":"","methodology":"Single case report of a 64-year-old female presenting with anomic aphasia while on semaglutide, with confirmed neurocysticercosis reactivation on brain imaging. The temporal relationship between semaglutide use and symptom onset, along with the known anti-neuroinflammatory effects of GLP-1 receptor agonists, was used to hypothesize the causal mechanism.","limitations":"This is a single case report — the lowest level of clinical evidence. The causal link between semaglutide and NCC reactivation is hypothetical and cannot be confirmed without larger observational studies. Other factors could have triggered the reactivation. The proposed mechanism (astrocyte/microglial modulation) is plausible but not proven in this case. Case reports can generate hypotheses but not establish risk levels."},{"rthcId":"RPEP-12885","title":"Effects of Semaglutide and Tirzepatide on Recurrent Weight Gain After Bariatric Surgery: A Systematic Review and Meta-analysis.","authors":"Osorio Manyari, Angel Alois; Armas Alvarez, Azucena Lirio; Osorio Manyari, Joel Davis; Onieva Gonzalez, Francisco; Pouwels, Sjaak","year":2025,"journal":"Obesity surgery, 35(12), 5596-5605","doi":"10.1007/s11695-025-08414-2","pmid":"41313431","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-12886","title":"Contemporary treatment patterns of overweight and obesity: insights from the Mass General Brigham health care system.","authors":"Ostrominski, John W; Wagholikar, Kavishwar B; Olsson, Kelly; Unlu, Ozan; Zelle, David; Kumar, Sanjay; Smith, Austen M; Toliver, Joshua C; Michalak, Wojciech; Fabricatore, Anthony; Hartaigh, Bríain Ó; Baer, Heather J; Cannon, Christopher P; Apovian, Caroline M; Fisher, Naomi D L; Plutzky, Jorge; Scirica, Benjamin M; Blood, Alexander J","year":2025,"journal":"Obesity (Silver Spring, Md.), 33(2), 365-384","doi":"10.1002/oby.24186","pmid":"39696750","tags":["weight-loss","semaglutide","liraglutide","glp-1","regulatory"],"studyType":"cross-sectional","evidenceStrength":"moderate","keyFinding":"Only 1.4% of the 1.1 million patients eligible for anti-obesity medications were actually prescribed them.","whyItMatters":"Reveals a massive treatment gap between guideline-eligible patients and actual prescribing, suggesting significant barriers to accessing obesity pharmacotherapy.","specificNumbers":"- 2,469,474 adults studied; 1,110,251 (45%) eligible for anti-obesity medication\n- Only 15,214 (1.4%) of eligible patients received a prescription\n- 69.4% of eligible patients had BMI of 30 or higher\n- Musculoskeletal disorders affected 54% of eligible patients\n- 62% of eligible patients had 2 or more obesity-related conditions\n- Liraglutide 3.0 mg: 58% of prescriptions; semaglutide 2.4 mg: 34%","methodology":"Cross-sectional analysis of electronic health records from a large multi-center U.S. health care system spanning 2018-2022.","limitations":"Single health system in the northeastern U.S. may not be nationally representative. Cannot determine why medications were not prescribed."},{"rthcId":"RPEP-12887","title":"Natriuretic Peptides, Body Mass Index, and Clinical Outcomes in Heart Failure With Mildly Reduced or Preserved Ejection Fraction.","authors":"Ostrominski, John W; Neuen, Brendon L; Claggett, Brian L; Anand, Inder S; Desai, Akshay S; Jhund, Pardeep S; Lam, Carolyn S P; Pfeffer, Marc A; Pitt, Bertram; Zannad, Faiez; Zile, Michael R; Packer, Milton; Docherty, Kieran F; McMurray, John J V; Solomon, Scott D; Vaduganathan, Muthiah","year":2025,"journal":"Journal of the American College of Cardiology, 86(20), 1823-1839","doi":"10.1016/j.jacc.2025.08.028","pmid":"40892613","tags":["natriuretic-peptides","cardiovascular","weight-loss"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"For the same absolute risk level, NT-proBNP levels in obese patients with HFpEF were significantly lower than in lean patients, suggesting BMI-adjusted thresholds are needed.","whyItMatters":"Heart failure diagnosis and clinical trial enrollment rely heavily on natriuretic peptide levels. If obesity suppresses these levels, many obese patients may be underdiagnosed or excluded from trials.","specificNumbers":"- 14,750 participants pooled from 4 trials; mean age 72, 50% female, mean BMI 30\n- Each doubling of NT-proBNP linked to 40% higher event rate (HR 1.40, 95% CI 1.36-1.43)\n- Same-risk NT-proBNP: 158 pg/mL at BMI 35+ vs 450 pg/mL at BMI <25 (about 3x lower)\n- Absolute risk at trial threshold: 3.5 per 100 person-years (BMI <25) vs 7.3 per 100 person-years (BMI 40+)\n- Median follow-up: 2.8 years","methodology":"Participant-level pooled analysis of 4 global randomized outcomes trials of adults with HFmrEF/HFpEF, with median follow-up of 2.8 years.","limitations":"Post-hoc pooled analysis; BMI is an imperfect measure of adiposity. Results may not apply to HF with reduced ejection fraction."},{"rthcId":"RPEP-12888","title":"Trends in Utilization of Glucose- and Weight-Lowering Medications After Tirzepatide Approval in the United States : A Population-Based Cohort Study.","authors":"Ostrominski, John W; Ortega-Montiel, Janinne; Tesfaye, Helen; Alix, Caroline; DiCesare, Elyse; Cromer, Sara J; Wexler, Deborah J; Paik, Julie M; Patorno, Elisabetta","year":2025,"journal":"Annals of internal medicine, 178(5), 620-633","doi":"10.7326/ANNALS-24-02870","pmid":"40228298","tags":["tirzepatide","semaglutide","weight-loss","diabetes","glp-1","regulatory"],"studyType":"retrospective-cohort","evidenceStrength":"moderate","keyFinding":"Tirzepatide reached 12.3% of diabetes medication dispensations and 40.6% of weight-loss medication dispensations within about 18 months of market entry.","whyItMatters":"Understanding prescribing trends helps gauge real-world adoption of new therapies and reveals how the treatment landscape for diabetes and obesity is shifting toward incretin-based medications.","specificNumbers":"- Tirzepatide reached 12.3% of all diabetes drug prescriptions by December 2023\n- Among weight-loss drugs, tirzepatide went from 0% to 40.6% of prescriptions in 18 months\n- Semaglutide 2.4 mg (Wegovy) grew from 0% to 32.2% in the same period\n- GLP-1 RAs overall grew from 19.5% to 28.5% of diabetes drug prescriptions\n- SGLT2 inhibitors grew from 14.5% to 24.4%","methodology":"Population-based cohort study analyzing commercial insurance claims data from a large U.S. database covering January 2021 to December 2023.","limitations":"Based on commercial insurance claims only, excluding uninsured and government-insured populations. Cannot assess clinical outcomes or reasons for prescribing choices."},{"rthcId":"RPEP-12889","title":"Efficacy and Safety of Tirzepatide Compared with GLP-1 RAs in Patients with Type 2 Diabetes Treated with Basal Insulin: A Network Meta-analysis.","authors":"Osumili, Beatrice; Sapin, Hélène; Yang, Zhengyu; Ranta, Kari; Paik, Jim S; Blüher, Matthias","year":2025,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 16(6), 1279-1311","doi":"10.1007/s13300-025-01728-5","pmid":"40214900","tags":["tirzepatide","glp-1","diabetes","dulaglutide","exenatide"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Tirzepatide at all doses (5, 10, 15 mg) significantly outperformed GLP-1 RAs for both blood sugar control and weight loss when combined with basal insulin.","whyItMatters":"Many type 2 diabetes patients need add-on therapy to insulin. This analysis suggests tirzepatide may offer superior benefits over existing GLP-1 drugs in this population.","specificNumbers":"- 6 randomized controlled trials included in the network meta-analysis\n- Tirzepatide at all 3 doses (5, 10, 15 mg) showed significantly greater HbA1c reduction vs all GLP-1 comparators\n- Tirzepatide at all 3 doses showed significantly greater weight reduction vs all GLP-1 comparators\n- No significant differences in treatment discontinuation rates vs GLP-1 comparators (except tirzepatide 10/15 mg vs placebo)","methodology":"Network meta-analysis of 6 randomized controlled trials comparing tirzepatide with GLP-1 RAs in patients on basal insulin.","limitations":"Indirect comparison via network meta-analysis, not head-to-head trials. Limited number of studies (6). Relatively short follow-up at primary endpoints."},{"rthcId":"RPEP-12890","title":"Growth differentiation factor-15 and N-terminal pro-BNP in acute heart failure with preserved ejection fraction.","authors":"Otaki, Yoichiro; Watanabe, Tetsu; Shimizu, Mari; Tachibana, Shingo; Sato, Junya; Kobayashi, Yuta; Tamura, Harutoshi; Kato, Shigehiko; Nishiyama, Satoshi; Takahashi, Hiroki; Arimoto, Takanori; Watanabe, Masafumi","year":2025,"journal":"ESC heart failure, 12(2), 888-899","doi":"10.1002/ehf2.15068","pmid":"39899430","tags":["natriuretic-peptides","cardiovascular"],"studyType":"prospective-cohort","evidenceStrength":"moderate","keyFinding":"GDF15 independently predicted heart failure events and improved prediction accuracy when combined with NT-proBNP (C-index improvement: 0.7190 to 0.7405).","whyItMatters":"Better risk prediction in HFpEF could help doctors identify which patients need more aggressive treatment and closer monitoring.","specificNumbers":"- 643 patients studied; mean age 73, 42% female\n- Median follow-up: about 5.5 years (1,998 days)\n- 132 heart failure events and 88 deaths during follow-up\n- GDF15 hazard ratio: 1.72 (95% CI 1.35-2.19, p<0.0001)\n- NT-proBNP hazard ratio: 1.63 (95% CI 1.25-2.13, p=0.0003)\n- Combined C-index improved from 0.719 to 0.741 (p=0.042)","methodology":"Prospective observational study of 643 HFpEF patients with median follow-up of 1,998 days (~5.5 years).","limitations":"Single-center observational study. Results need validation in diverse populations. GDF15 is not specific to heart failure."},{"rthcId":"RPEP-12891","title":"Antimicrobial peptides (AMPs) of lizards: a first comprehensive characterization of beta-defensins, ovo-defensins and cathelicidins from Podarcis lilfordi and closely related Lacertidae species.","authors":"Otalora, Katherin; Gómez-Garrido, Jessica; Baldo, Laura","year":2025,"journal":"BMC genomics, 26(1), 677","doi":"10.1186/s12864-025-11797-2","pmid":"40691529","tags":["antimicrobial-peptides","ll-37","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"75 antimicrobial peptides identified in one lizard species—far more diverse than expected—with consistent chromosomal organization across multiple species.","whyItMatters":"Reptiles' remarkable infection resistance may be explained by this rich antimicrobial peptide arsenal, offering potential templates for developing new antibiotics.","specificNumbers":"- 75 AMPs identified in Podarcis lilfordi: 63 beta-defensins, 8 ovo-defensins, 4 cathelicidins\n- 58 AMPs identified across 3 additional lizard species\n- All AMPs located on chromosome 3 (defensins) and chromosome 12 (cathelicidins)\n- Multiple instances of identical peptides found across distantly related lizard families","methodology":"Computational genome mining of published Lacertidae genomes with ortholog identification across 4 lizard species.","limitations":"Genome mining identifies sequences but does not confirm functional antimicrobial activity. Expression levels and in vivo roles need experimental validation."},{"rthcId":"RPEP-12892","title":"Characteristics and management of headache among psychiatric outpatients at a Japanese general hospital: A retrospective study with an exploratory CGRP case series.","authors":"Otani, Kyohei; Imbe, Nobuyasu; Shindo, Ryota","year":2025,"journal":"PCN reports : psychiatry and clinical neurosciences, 4(4), e70235","doi":"10.1002/pcn5.70235","pmid":"41181353","tags":["neuropeptides","pain","anxiety-mood"],"studyType":"retrospective-cohort","evidenceStrength":"preliminary","keyFinding":"14.3% of psychiatric outpatients had headache diagnoses, with the majority managed within psychiatry departments rather than neurology.","whyItMatters":"Headache in psychiatric patients is often attributed to their mental condition and undertreated. CGRP therapies may offer new options for these patients.","specificNumbers":"- 2,525 psychiatric outpatients reviewed; 360 (14.3%) had headache diagnoses\n- Headache types: generic headache 56.4%, migraine 25.6%, tension-type 12.8%\n- Psychiatry managed 42.5% of headache cases; neurology managed 11.7%\n- 7 patients received CGRP antibodies; all had headache improvement\n- Mean age of CGRP patients: 48.4 years; 6 of 7 were women","methodology":"Retrospective chart review of all psychiatric outpatients at a 600-bed Japanese general hospital over one year, with an exploratory CGRP case series.","limitations":"Retrospective chart review in a single center. Headache diagnoses via insurance codes may be inaccurate. CGRP case series was exploratory with few patients."},{"rthcId":"RPEP-12893","title":"Semaglutide in Patients with Obesity and Heart Failure Irrespective of Their Baseline Ejection Fraction: An Efficacy and Safety Meta-analysis of Randomized Controlled Trials.","authors":"Otmani, Zina; Elsayed, Hazem Ayman; Yassin, Mazen Negmeldin Aly; Saihi, Mohamed Jalil; Aldemerdash, Mohamed A; Alzawahreh, Ahmad; Hassan, Amr; Alahmed, Farouq Bahaa; Gonnah, Ahmed R; Abdelaziz, Ahmed","year":2025,"journal":"Cardiology in review","doi":"10.1097/CRD.0000000000000925","pmid":"40310127","tags":["semaglutide","cardiovascular","weight-loss"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Semaglutide reduced cardiovascular mortality by 26% overall (RR 0.74), with a 34% reduction in HFrEF patients.","whyItMatters":"This is among the first evidence that GLP-1 receptor agonists may directly reduce cardiovascular death in heart failure patients, not just improve symptoms.","specificNumbers":"- 5 RCTs, 6,898 total patients\n- Cardiovascular death: 26% reduction (RR 0.74, 95% CI 0.58-0.94, p=0.02)\n- HFrEF subgroup: 34% reduction (RR 0.66, p=0.01)\n- HFpEF subgroup: 16% reduction (RR 0.84, p=0.37, not significant)\n- Quality of life (KCCQ-CSS): improved by 7.72 points (p<0.001)\n- 6-minute walk distance: improved by 14.83 meters (p=0.006)","methodology":"Meta-analysis of 5 randomized controlled trials totaling 6,898 patients, with subgroup analysis by ejection fraction.","limitations":"Meta-analysis with heterogeneous trial designs. HFpEF benefit did not reach significance. Relatively short follow-up in some trials."},{"rthcId":"RPEP-12894","title":"Pulmonary Hypertension Associated with Severe Interstitial Pneumonia Successfully Treated with Inhaled Treprostinil: A Case Report.","authors":"Otsuka, Mitsuki; Sonoda, Shiro; Yamada, Takayuki; Aoki, Shotaro; Yasuda, Tomoka; Sawada, Atsushi; Shirai, Tsuyoshi; Tateishi, Tomoya; Furusawa, Haruhiko; Miyazaki, Yasunari","year":2025,"journal":"Internal medicine (Tokyo, Japan)","doi":"10.2169/internalmedicine.6206-25","pmid":"41034006","tags":["natriuretic-peptides","cardiovascular","respiratory"],"studyType":"case-report","evidenceStrength":"preliminary","keyFinding":"Inhaled treprostinil improved BNP levels, tricuspid pressure gradient, and oxygen requirements in a patient with severe interstitial pneumonia and pulmonary hypertension.","whyItMatters":"Demonstrates real-world effectiveness of inhaled treprostinil in a difficult-to-treat patient with combined severe lung disease and pulmonary hypertension.","specificNumbers":"- Patient age: 72 years\n- Maximum TRPG before treatment: 64 mmHg\n- BNP levels and TRPG improved after inhaled treprostinil\n- Oxygen requirement decreased after treatment","methodology":"Single case report of a 72-year-old male patient.","limitations":"Single case report cannot establish efficacy. Spontaneous improvement or concurrent treatments may have contributed."},{"rthcId":"RPEP-12895","title":"Fatty Pancreas: Its Potential as a Risk Factor for Pancreatic Cancer and Clinical Implications.","authors":"Otsuka, Nao; Shimamatsu, Yutaka; Hakuta, Ryunosuke; Takayama, Yukiko; Nakai, Yousuke","year":2025,"journal":"Cancers, 17(11)","doi":"10.3390/cancers17111765","pmid":"40507246","tags":["glp-1","cancer","diabetes","liver"],"studyType":"narrative-review","evidenceStrength":"preliminary","keyFinding":"Fatty pancreas may be linked to increased risk of pancreatic ductal adenocarcinoma through chronic inflammation and lipotoxicity, and certain diabetes drugs might help.","whyItMatters":"Pancreatic cancer has very poor survival. If fatty pancreas is a modifiable risk factor, it could open new prevention strategies.","specificNumbers":"- No specific numerical results reported in abstract\n- GLP-1 receptor agonists and SGLT2 inhibitors mentioned as potential interventions\n- Fatty pancreas linked to obesity, insulin resistance, and diabetes","methodology":"Narrative literature review of imaging studies, metabolic research, and pharmacological evidence.","limitations":"Narrative review; no meta-analysis. Causation between fatty pancreas and cancer is not established. GLP-1 effects on pancreatic fat need controlled trials."},{"rthcId":"RPEP-12896","title":"GLP-1R Agonists Improve Ocular Surface Parameters in Type 2 Diabetes Mellitus.","authors":"Ottonelli, Giovanni; Gaeta, Alessandro; Montericcio, Novella; Tredici, Costanza; Ortfeldt, Vittoria; Birtolo, Maria Francesca; Jaafar, Simona; Mirani, Marco; Di Maria, Alessandra","year":2025,"journal":"Clinical ophthalmology (Auckland, N.Z.), 19, 3829-3836","doi":"10.2147/OPTH.S547776","pmid":"41116973","tags":["glp-1","eye-health","diabetes"],"studyType":"case-control","evidenceStrength":"preliminary","keyFinding":"GLP-1 RA users had median Schirmer values of 15 mm vs. 7.5 mm and median TBUT of 10 sec vs. 5.85 sec compared to non-users.","whyItMatters":"Dry eye disease is very common in diabetes patients. If GLP-1 medications improve ocular surface health, this is an important additional benefit to consider.","specificNumbers":"- 35 patients: 21 on GLP-1 RAs, 14 on other diabetes drugs\n- Schirmer test: 15 mm (GLP-1) vs 7.5 mm (control), p=0.016\n- Tear breakup time: 10 sec (GLP-1) vs 5.85 sec (control), p=0.016","methodology":"Single-center case-control study of 35 patients with type 2 diabetes.","limitations":"Very small sample size (35 patients). Single center. Case-control design cannot prove causation. Groups may differ in ways not accounted for."},{"rthcId":"RPEP-12897","title":"X-ray fluorescence analysis of elemental content of snake venoms.","authors":"Oubkeo, Crystal; Ng, Kaitlyn; Reiser, Kristofer; VanEthen, Zoe; Mackessy, Stephen P; Apawu, Aaron K","year":2025,"journal":"Toxicon : official journal of the International Society on Toxinology, 264, 108457","doi":"10.1016/j.toxicon.2025.108457","pmid":"40499789","tags":["venom-peptides","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Neonate rattlesnake venom contained 5-7 times more potassium than adult venom, potentially enhancing the toxicity of smaller venom volumes.","whyItMatters":"Understanding venom elemental composition helps explain how venom toxins function and may aid in developing antivenoms and biomedical applications.","specificNumbers":"- Dominant elements: sulfur and potassium (high), calcium and zinc (moderate)\n- Neonate C. viridis viridis potassium: 5-7x higher than adults\n- Neonate C. polystictus potassium: also higher than adults\n- 2 rattlesnake species analyzed: C. polystictus (Mexico) and C. viridis viridis (Colorado, USA)","methodology":"X-ray fluorescence spectroscopy analysis of snake venoms from two Crotalus species, comparing age and sex differences.","limitations":"Two species studied; limited sample sizes. Functional significance of elemental differences is hypothesized but not experimentally confirmed."},{"rthcId":"RPEP-12898","title":"Left atrial changes and B-type natriuretic peptide levels after pulmonary vein isolation for atrial fibrillation.","authors":"Ouchi, Kotaro; Sakuma, Toru; Kisaki, Shunsuke; Tokutake, Kenichi; Yamane, Teiichi; Ojiri, Hiroya; Yoshimura, Michihiro","year":2025,"journal":"International journal of cardiology, 425, 133053","doi":"10.1016/j.ijcard.2025.133053","pmid":"39952475","tags":["natriuretic-peptides","cardiovascular"],"studyType":"retrospective-cohort","evidenceStrength":"moderate","keyFinding":"PVI significantly reduced left atrial volume and improved ejection fraction, with corresponding decreases in BNP levels.","whyItMatters":"Understanding how ablation affects cardiac structure and biomarkers helps clinicians assess treatment success and predict outcomes.","specificNumbers":"- 228 patients; mean age 61.4 years\n- BNP, maximum and minimum LAV/BSA all decreased significantly after PVI (p<0.05)\n- BNP positively correlated with left atrial volume (p<0.001)\n- BNP negatively correlated with left atrial ejection fraction (p<0.001)","methodology":"Retrospective analysis of 228 AF patients with cardiac CT and BNP measurements before and after PVI.","limitations":"Retrospective single-center study. No control group. Cannot separate effects of rhythm restoration from structural remodeling."},{"rthcId":"RPEP-12899","title":"Prior metabolic surgery attenuates the weight-loss efficacy of liraglutide in patients with mild obesity.","authors":"Ouyang, Yuqin; Xiang, Xinyue; Hu, Xinyun; Chu, Xuehui; Tang, Wenjuan; Feng, Wenhuan","year":2025,"journal":"Frontiers in endocrinology, 16, 1580159","doi":"10.3389/fendo.2025.1580159","pmid":"40475994","tags":["liraglutide","weight-loss"],"studyType":"retrospective-cohort","evidenceStrength":"preliminary","keyFinding":"Prior metabolic surgery was associated with a 6.78x higher odds of poor response to liraglutide for weight loss.","whyItMatters":"As more patients have histories of both bariatric surgery and GLP-1 medication use, understanding interactions between these approaches is critical for treatment planning.","specificNumbers":"- 64 adults, BMI 28-32.5, 12-week liraglutide treatment\n- Responders: 37 (57.8%); non-responders: 27 (42.2%)\n- Responder weight loss: 11.0% (9.04 kg) vs non-responder: 4.2% (3.55 kg)\n- Prior metabolic surgery: OR 6.78 for non-response (95% CI 1.95-23.61, p<0.01)\n- BMI 30.5+: OR 4.79 for non-response (95% CI 1.46-15.71, p<0.01)","methodology":"Retrospective analysis of 64 adults with mild obesity on a 12-week liraglutide intervention.","limitations":"Small sample size (64 patients). Retrospective design. Short 12-week duration. No details on type of prior metabolic surgery."},{"rthcId":"RPEP-12900","title":"Effectiveness for adding or switching from other incretin-related drugs to oral semaglutide in type 2 diabetes.","authors":"Oya, Junko; Shimizu, Mika; Kubota, Ryo; Suda, Rika; Nagkagami, Tomoko","year":2025,"journal":"Journal of diabetes investigation, 16(4), 608-614","doi":"10.1111/jdi.14391","pmid":"39707717","tags":["semaglutide","diabetes","oral-peptides","glp-1","dulaglutide"],"studyType":"retrospective-cohort","evidenceStrength":"moderate","keyFinding":"Oral semaglutide reduced HbA1c by 0.85% in naive patients, 0.67% in DPP-4i switchers, and 0.13% in GLP-1 RA switchers.","whyItMatters":"Many patients switch between diabetes medications. Understanding how prior therapy affects oral semaglutide's effectiveness helps guide treatment decisions.","specificNumbers":"- 368 participants with type 2 diabetes\n- HbA1c change: naive group -0.85%, DPP-4 switch -0.67%, GLP-1 switch -0.13%\n- DPP-4 and GLP-1 switch groups had significantly smaller HbA1c reductions vs naive (p significant)\n- GLP-1 switch group lost less weight than naive group\n- Dulaglutide-to-oral-semaglutide switch produced more weight loss than injectable-semaglutide-to-oral switch","methodology":"Retrospective real-world analysis of 368 Japanese patients divided by prior incretin medication use.","limitations":"Retrospective study in Japanese patients; may not generalize. Relatively short 6-month follow-up. No randomization."},{"rthcId":"RPEP-12901","title":"Neoantigen peptide-pulsed dendritic cell vaccine therapy after surgical treatment of pancreatic cancer: a retrospective study.","authors":"Oyama, Koki; Nakata, Kohei; Abe, Toshiya; Hirotaka, Kento; Fujimori, Nao; Kiyotani, Kazuma; Iwamoto, Chika; Ikenaga, Naoki; Morisaki, Shinji; Umebayashi, Masayo; Tanaka, Hiroto; Koya, Norihiro; Nakagawa, Shinichiro; Tsujimura, Kenta; Yoshimura, Sachiko; Onishi, Hideya; Nakamura, Yusuke; Nakamura, Masafumi; Morisaki, Takashi","year":2025,"journal":"Frontiers in immunology, 16, 1571182","doi":"10.3389/fimmu.2025.1571182","pmid":"40248703","tags":["cancer","immune-function","peptide-design"],"studyType":"retrospective-cohort","evidenceStrength":"preliminary","keyFinding":"81.3% of patients developed neoantigen-specific immune responses; only 1 of 7 patients receiving adjuvant vaccination had recurrence over 5+ years.","whyItMatters":"Pancreatic cancer has extremely poor prognosis and resists most immunotherapies. This personalized approach shows early but promising results.","specificNumbers":"- 16 patients received the vaccine; 81.3% (13/16) developed neoantigen-specific T cells\n- 7 adjuvant patients: only 1 recurrence, no deaths, median follow-up 61 months\n- 9 patients treated after recurrence: longer survival with T cell induction vs without\n- One case showed a dominant CD4+ T cell clone induced by long peptides","methodology":"Retrospective study of 16 patients who received personalized neoantigen peptide-pulsed dendritic cell vaccines after pancreatic cancer surgery.","limitations":"Very small retrospective study without a control group. Cannot establish efficacy without randomized trials."},{"rthcId":"RPEP-12902","title":"The effects of the GLP1 analog liraglutide on allodynia and motor coordination in peripheral neuropathy induced by a chemotherapeutic agent, cisplatin.","authors":"Ozatik, Fikriye Yasemin; Teksen, Yasemin; Ozatik, Orhan; Çengelli Unel, Cigdem; Karadeniz Saygili, Suna","year":2025,"journal":"Journal of molecular histology, 56(3), 153","doi":"10.1007/s10735-025-10440-4","pmid":"40341588","tags":["liraglutide","neuroprotection","pain","glp-1","inflammation"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Liraglutide, especially at weekly dosing, reduced cisplatin-induced neuropathic pain, motor impairment, and nerve tissue damage in rats.","whyItMatters":"Chemotherapy-induced peripheral neuropathy affects many cancer patients and has no effective treatment. GLP-1 agonists could address this unmet need.","specificNumbers":"- 32 rats in 4 groups of 8\n- Cisplatin dose: 3 mg/kg/week for 5 weeks\n- Liraglutide given once weekly or daily\n- Weekly liraglutide was more effective than daily\n- Markers measured: SOD, CAT, GPx (oxidative stress); NO, IL-6, IL-10 (inflammation)","methodology":"Preclinical study in 32 female Sprague Dawley rats divided into 4 groups with behavioral, biochemical, and histological analysis.","limitations":"Animal study; results may not translate to humans. Only one chemotherapy agent tested. Small group sizes."},{"rthcId":"RPEP-12903","title":"Gender-Based Differences in COPD Patients with Type 2 Respiratory Failure-Impact on Clinical Practice.","authors":"Ozdemir, Tarkan; Yıldız, Murat; Arı, Maşide; Arı, Emrah; Eraslan Doğanay, Güler; Cırık, Mustafa Özgür; Doğancı, Melek; Özdilekcan, Çiğdem; Kızılgöz, Derya; Şipit, Yusuf Tuğrul","year":2025,"journal":"Medicina (Kaunas, Lithuania), 61(4)","doi":"10.3390/medicina61040587","pmid":"40282878","tags":["natriuretic-peptides","cardiovascular","respiratory"],"studyType":"cross-sectional","evidenceStrength":"moderate","keyFinding":"Female COPD ICU patients had significantly higher rates of heart failure, obesity, and elevated BNP levels compared to males.","whyItMatters":"Gender differences in COPD presentation and comorbidities affect treatment strategies and outcomes in critical care settings.","specificNumbers":"- 258 patients: 91 female (35%), 167 male (65%)\n- Women had significantly higher BNP and D-dimer levels\n- Women had higher rates of heart failure, atrial fibrillation, hypertension, renal disease\n- Women had higher Charlson Comorbidity Index scores\n- Women had higher BMI and more morbid obesity\n- Women had higher pre-discharge PaCO2 levels","methodology":"Prospective, observational cross-sectional study of 258 COPD patients admitted to ICU with type 2 respiratory failure.","limitations":"Single-center observational study. Cross-sectional design cannot establish causation. Potential confounders not fully controlled."},{"rthcId":"RPEP-12904","title":"Bromelain Improves Hypothalamic Control of Energy Homeostasis in High-Fat Diet-Induced Obese Rats.","authors":"Ozen Koca, Raviye; Basaran, Mustafa Berk; Solak, Hatice; Solak Gormus, Zulfikare Isik","year":2025,"journal":"Current issues in molecular biology, 47(8)","doi":"10.3390/cimb47080607","pmid":"40864762","tags":["neuropeptides","weight-loss","bioactive-food-peptides"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Bromelain restored GLUT2 and normalized POMC and IGF1R expression in hypothalamic tissue of obese rats.","whyItMatters":"Central (brain) regulation of appetite and metabolism is disrupted in obesity. Natural compounds that restore this regulation could complement weight-loss therapies.","specificNumbers":"- 36 male Wistar rats in 4 groups of 9\n- Bromelain dose: 200 mg/kg/day orally for 1 month\n- GLUT2 downregulated by HFD, significantly restored by bromelain\n- POMC elevated by HFD, normalized by bromelain\n- IGF1R elevated by HFD, reduced by bromelain\n- NPY and FGF2: no significant changes with bromelain","methodology":"Preclinical study in 36 male Wistar rats across 4 diet/treatment groups with hypothalamic ELISA analysis.","limitations":"Animal study with a small number of subjects per group. Short treatment duration. Cannot be directly translated to human obesity treatment."},{"rthcId":"RPEP-12905","title":"Association of plasma BNP levels at different times with cardioversion success, maintenance of sinus rhythm and severity of diastolic dysfunction in patients with atrial fibrillation.","authors":"Ozturk, Ali; Okan, Taha","year":2025,"journal":"Cardiovascular journal of Africa, 36(1), 6-11","doi":"10.5830/CVJA-2024-009","pmid":"40779155","tags":["natriuretic-peptides","cardiovascular"],"studyType":"prospective-cohort","evidenceStrength":"preliminary","keyFinding":"Post-cardioversion BNP at 30 minutes, not baseline BNP, predicted early AF recurrence. Higher BNP was associated with worse diastolic dysfunction.","whyItMatters":"Predicting which AF patients will relapse after cardioversion could help guide more targeted treatment decisions.","specificNumbers":"- 31 patients with persistent AF; 28 successfully cardioverted\n- 30-minute BNP in AF recurrence group: 318 ± 39.7 pg/mL\n- 30-minute BNP in maintained rhythm group: 153 ± 11.9 pg/mL (p=0.05)\n- Baseline BNP: not predictive of recurrence\n- BNP correlated with heart rate and E/Em ratio","methodology":"Prospective observational study of 31 patients with persistent AF, with echocardiography and BNP at multiple time points.","limitations":"Very small sample size (31 patients). Single center. Short follow-up (1 month). Results need validation in larger cohorts."},{"rthcId":"RPEP-12906","title":"Osteogenic effects of metformin and exenatide on bone regeneration in non-diabetic rats: A Micro-CT and histological study.","authors":"Ozturk, Hasan; Simsek, Neslihan; Akinci, Levent; Ozgocmen, Meltem; Yigit, Dilek Helvacioglu","year":2025,"journal":"Journal of oral and maxillofacial pathology : JOMFP, 29(3), 352-359","doi":"10.4103/jomfp.jomfp_4_25","pmid":"41069630","tags":["exenatide","bone-joint","glp-1"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Metformin and exenatide significantly increased osteoblast and osteoclast numbers at bone defect sites (p=0.007 for both) without affecting overall bone volume.","whyItMatters":"If diabetes drugs can enhance bone healing, this could benefit patients with fractures or bone defects, particularly those already taking these medications.","specificNumbers":"- 27 rats in 3 groups of 9\n- Metformin dose: 100 mg/kg/day orally\n- Exenatide dose: 3 microg/kg/day intraperitoneally\n- Osteoblast count: significantly higher in both drug groups (p=0.007)\n- Osteoclast count: significantly higher in both drug groups (p=0.007)\n- Bone volume, density, integration: no significant differences","methodology":"Preclinical study in 27 female Wistar rats with cranial bone defects, analyzed by micro-CT and histology.","limitations":"Animal study with small groups. No significant difference in bone volume or density. Short observation period."},{"rthcId":"RPEP-12907","title":"Effects of weight-loss interventions on bone health in people living with obesity.","authors":"Paccou, Julien; Gagnon, Claudia; Yu, Elaine W; Rosen, Clifford J","year":2025,"journal":"Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 40(12), 1319-1331","doi":"10.1093/jbmr/zjaf135","pmid":"41042228","tags":["glp-1","semaglutide","liraglutide","bone-joint","weight-loss"],"studyType":"narrative-review","evidenceStrength":"moderate","keyFinding":"All weight-loss interventions increase bone turnover; bariatric surgery is worst for bone health. GLP-1 drugs show mixed signals—protective in animals at high doses but potentially harmful during significant human weight loss.","whyItMatters":"With millions of people using GLP-1 drugs for weight loss, understanding bone safety is critical, especially for patients already at fracture risk.","specificNumbers":"- No specific statistical results reported\n- Two RCTs have tested anti-osteoporosis medications post-bariatric surgery\n- Animal studies used liraglutide doses higher than human-approved doses\n- Multiple mechanisms identified for post-surgical bone loss","methodology":"Narrative review of preclinical and clinical evidence on bone effects of calorie restriction, bariatric surgery, and GLP-1 receptor agonists.","limitations":"Narrative review with heterogeneous study types. Animal dose levels far exceed human therapeutic doses. Long-term human fracture data are limited."},{"rthcId":"RPEP-12908","title":"Glucagon-like peptide-1 receptor agonism improves lung cancer outcomes and tumor growth control.","authors":"Pachimatla, Akhil Goud; Fitzgerald, Bailey; Ogidigo, Joyce; Bhatia, Meera; Smith, Randall J; Ratnakaram, Kalyan; Kalvapudi, Sukumar; Vedire, Yeshwanth; Washington, Deschana; Vethanayagam Rr, Robert; Hsiao, Hua-Hsin; Rosario, Spencer; Sanghvi, Viraj R; Barbi, Joseph; Yendamuri, Sai","year":2025,"journal":"JCI insight, 10(19)","doi":"10.1172/jci.insight.195484","pmid":"40857107","tags":["glp-1","cancer","immune-function","weight-loss"],"studyType":"retrospective-cohort","evidenceStrength":"moderate","keyFinding":"GLP-1 receptor agonist use was associated with a 59% reduction in the hazard of recurrence or death after lung cancer surgery (HR 0.41), and a 69% reduction in the hazard of progression when added to immunotherapy, in overweight and obese patients.","whyItMatters":"Obesity worsens lung cancer prognosis, and immunotherapy is only partially effective. If GLP-1 drugs can reprogram the tumor immune microenvironment in obese patients, they could become an inexpensive add-on to existing cancer treatment—leveraging a medication millions already take.","specificNumbers":"- Surgical cohort: 1,177 patients, 71 GLP-1 users; recurrence HR 0.41 (95% CI 0.16-1.04, p=0.026)\n- Immunotherapy cohort: 300 patients, 10 GLP-1 users; overall survival HR 0.41 (p=0.027); progression-free survival HR 0.31 (p=0.019)\n- Mouse studies: tumor reduction in obese mice only","methodology":"Propensity-score-matched retrospective analysis of two clinical cohorts (surgical resection n=1,177; immunotherapy n=300) plus mechanistic mouse model experiments in obese and normal-weight mice.","limitations":"Small number of GLP-1 users in each cohort (especially only 10 in the immunotherapy group) limits statistical power. Retrospective design introduces potential unmeasured confounders. Mouse results may not translate directly to humans. Obesity definition varies."},{"rthcId":"RPEP-12909","title":"What will the impact be of use of tirzepatide in patients with obstructive sleep apnea (OSA)?","authors":"Pack, Allan; Grunstein, Ronald; Mokhlesi, Babak; Ryan, Silke; Schwab, Richard; Gozal, David","year":2025,"journal":"Sleep, 48(6)","doi":"10.1093/sleep/zsaf045","pmid":"40184186","tags":["tirzepatide","weight-loss","respiratory"],"studyType":"review","evidenceStrength":"strong","keyFinding":"About 50% of obese patients with OSA achieved resolution of their condition with tirzepatide over 52 weeks.","whyItMatters":"Sleep apnea affects hundreds of millions worldwide. A drug that can resolve it in half of patients could fundamentally change treatment paradigms.","specificNumbers":"- Approximately 50% of patients had OSA resolution on tirzepatide\n- Treatment period: 52 weeks\n- Primary endpoint: change in apnea-hypopnea index (AHI)","methodology":"Expert forum commentary on the SURMOUNT-OSA randomized controlled trial results.","limitations":"Expert opinion piece; trial results from a selected population. Long-term outcomes, adherence, and cost-effectiveness unknown."},{"rthcId":"RPEP-12910","title":"Influence of Type 2 Diabetes on the Effects of Tirzepatide in Patients With Heart Failure and a Preserved Ejection Fraction With Obesity: A Prespecified Stratification-Based Analysis.","authors":"Packer, Milton; Zile, Michael R; Kramer, Christopher M; DiMaria, Joseph M; Baum, Seth J; Litwin, Sheldon E; Murakami, Masahiro; Zhou, Chunmei; Ou, Yang; Koeneman, Lisette; Borlaug, Barry A","year":2025,"journal":"Journal of the American College of Cardiology, 86(10), 696-707","doi":"10.1016/j.jacc.2025.06.058","pmid":"40903131","tags":["tirzepatide","cardiovascular","diabetes","weight-loss"],"studyType":"randomized-controlled-trial","evidenceStrength":"strong","keyFinding":"Tirzepatide benefits for heart failure were consistent regardless of diabetes status: HR 0.64 with diabetes vs. 0.61 without diabetes.","whyItMatters":"Since many HFpEF patients have diabetes and diabetes often attenuates weight-loss drug effects, confirming that tirzepatide works equally in both groups is clinically important.","specificNumbers":"- 731 patients randomized; median follow-up 104 weeks\n- Overall composite endpoint HR: 0.62 (95% CI 0.41-0.95, p=0.026)\n- With diabetes HR: 0.64 (95% CI 0.35-1.15)\n- Without diabetes HR: 0.61 (95% CI 0.33-1.10); interaction p=0.95\n- Weight loss: 10.4% (diabetes) vs 12.9% (no diabetes); interaction p=0.04\n- Similar reductions in left ventricular mass and paracardiac fat in both groups","methodology":"Pre-specified stratification analysis of the SUMMIT double-blind RCT with 731 patients, median 104-week follow-up.","limitations":"Sub-analysis of a larger trial; not powered for subgroup comparisons. Relatively modest sample size for subgroup analyses."},{"rthcId":"RPEP-12911","title":"Interplay of Chronic Kidney Disease and the Effects of Tirzepatide in Patients With Heart Failure, Preserved Ejection Fraction, and Obesity: The SUMMIT Trial.","authors":"Packer, Milton; Zile, Michael R; Kramer, Christopher M; Murakami, Masahiro; Ou, Yang; Borlaug, Barry A","year":2025,"journal":"Journal of the American College of Cardiology, 85(18), 1721-1735","doi":"10.1016/j.jacc.2025.03.009","pmid":"40162940","tags":["tirzepatide","cardiovascular","kidney"],"studyType":"randomized-controlled-trial","evidenceStrength":"strong","keyFinding":"Tirzepatide improved heart failure outcomes equally in patients with and without CKD, but creatinine-based eGFR appeared to decline on tirzepatide while cystatin C-based eGFR improved—indicating the creatinine decline is an artifact of muscle loss from weight reduction, not true kidney deterioration.","whyItMatters":"Millions of patients with obesity have both CKD and HFpEF simultaneously. Understanding that tirzepatide benefits extend to CKD patients—and that conventional kidney tests may mislead clinicians about drug safety—has immediate clinical relevance for monitoring and prescribing decisions.","specificNumbers":"- 731 SUMMIT trial patients, enriched for CKD\n- CKD patients had 2x risk of worsening heart failure events\n- Baseline eGFR-cystatin C was ~9 mL/min/1.73m2 lower than eGFR-creatinine\n- Tirzepatide improved eGFR at 52 weeks by both measures\n- eGFR-creatinine dipped at 12 weeks then recovered; eGFR-cystatin C improved throughout","methodology":"Pre-specified sub-analysis of the SUMMIT RCT (n=731); CKD subgroup analyses stratified by creatinine- and cystatin C-based eGFR; eGFR measured at baseline, 12, 24, and 52 weeks; KCCQ-CSS and cardiovascular outcomes as endpoints.","limitations":"Subgroup analysis from an RCT—not powered for CKD-specific endpoints. Cystatin C measurement was not part of the original trial design and required post-hoc analysis. Generalizability to non-obese or non-HFpEF CKD populations is unclear."},{"rthcId":"RPEP-12912","title":"Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity.","authors":"Packer, Milton; Zile, Michael R; Kramer, Christopher M; Baum, Seth J; Litwin, Sheldon E; Menon, Venu; Ge, Junbo; Weerakkody, Govinda J; Ou, Yang; Bunck, Mathijs C; Hurt, Karla C; Murakami, Masahiro; Borlaug, Barry A","year":2025,"journal":"The New England journal of medicine, 392(5), 427-437","doi":"10.1056/NEJMoa2410027","pmid":"39555826","tags":["tirzepatide","cardiovascular","weight-loss"],"studyType":"randomized-controlled-trial","evidenceStrength":"strong","keyFinding":"Tirzepatide reduced the composite of cardiovascular death or worsening heart failure events by 38% (HR 0.62, p=0.026), and produced a 15% body weight reduction along with clinically meaningful improvements in quality-of-life scores and 6-minute walk distance.","whyItMatters":"HFpEF is the most common form of heart failure and has almost no proven disease-modifying treatments. Tirzepatide is already approved for diabetes and obesity; this trial opens a new therapeutic indication with significant public health impact, given that obesity is the dominant driver of HFpEF.","specificNumbers":"- 731 patients randomized (364 tirzepatide, 367 placebo)\n- Median follow-up: 104 weeks\n- CV death or worsening HF: 9.9% vs 15.3% (HR 0.62, p=0.026)\n- Worsening HF alone: 8.0% vs 14.2% (HR 0.54)\n- CV death: 2.2% vs 1.4% (HR 1.58, not significant, very few events)\n- KCCQ-CSS improvement: 19.5 vs 12.7 points (difference 6.9, p<0.001)\n- GI-related discontinuation: 6.3% vs 1.4%","methodology":"International, double-blind, placebo-controlled randomized trial (SUMMIT) enrolling 731 patients; 1:1 randomization to tirzepatide (up to 15 mg/week subcutaneously) or placebo; median 104 weeks follow-up; two co-primary endpoints.","limitations":"Enrolled patients were enriched for obesity-related HFpEF; results may not apply to HFpEF with other causes. Event rates were lower than expected, meaning the trial may have been underpowered for cardiovascular mortality alone. Longer-term durability unknown."},{"rthcId":"RPEP-12913","title":"AI-driven antimicrobial peptide characterization unveils novel motifs for drug design.","authors":"Padi, Sarala; Mondal, Kinjal; Hoogerheide, David P; Heinrich, Frank; Mihailescu, Mihaela; Klauda, Jeffery B; Cardone, Antonio","year":2025,"journal":"Scientific reports, 16(1), 829","doi":"10.1038/s41598-025-30419-1","pmid":"41461873","tags":["antimicrobial-peptides","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Topic model-derived AMP motifs were more strongly associated with antimicrobial activity and demonstrated lower minimum inhibitory concentration values than traditional frequency-based motifs, suggesting the AI approach identifies more biologically relevant antimicrobial patterns.","whyItMatters":"Drug-resistant infections are a global health crisis. Better computational tools for identifying potent AMP motifs could accelerate the discovery of new antimicrobials—potentially reducing the time and cost of antibiotic development from decades to years.","specificNumbers":"- AI-derived motifs had lower MIC values than traditional motifs\n- Topic models captured contextual relationships missed by frequency analysis\n- Structural predictions validated using Evolutionary Scale Modeling (ESM)","methodology":"In silico/computational study applying topic models (unsupervised machine learning) to antimicrobial peptide sequence databases; motif extraction compared against frequency-based approaches; structural validation via ESM; biochemical property analysis.","limitations":"In silico study only—no wet lab validation of predicted peptides against live bacteria. Topic model results depend on the quality and diversity of the training AMP dataset. Minimum inhibitory concentrations were computationally predicted, not measured experimentally."},{"rthcId":"RPEP-12914","title":"Assessment of Functional Status of Human Leukocyte Antigen Class I Genes in Cancer Tissues in the Context of Personalized Neoantigen Peptide Vaccine Immunotherapy.","authors":"Padul, Vijay G; Biswas, Nupur; Gill, Mini; Perez, Jesus A; Lopez, Javier J; Kesari, Santosh; Ashili, Shashanka","year":2025,"journal":"JCO clinical cancer informatics, 9, e2400174","doi":"10.1200/CCI-24-00174","pmid":"40601881","tags":["cancer","peptide-design","immune-function"],"studyType":"cross-sectional","evidenceStrength":"preliminary","keyFinding":"Among 24 cancer patients, somatic HLA class I gene mutations were found in 5 patients, HLA gene loss of heterozygosity in 5 patients, and chromosome 6 copy loss in 8 patients—indicating over half had some form of HLA gene disruption that could undermine personalized neoantigen vaccine therapy.","whyItMatters":"Personalized cancer vaccines are a cutting-edge treatment with enormous promise, but variable response rates. If HLA gene disruption is common in tumors and routinely overlooked, it explains why some patients fail to respond—and points to a simple diagnostic step that could improve patient selection.","specificNumbers":"- 24 patients analyzed with paired tumor-normal sequencing\n- 5 patients (20.8%) had somatic HLA mutations in tumor\n- 5 patients (20.8%) had HLA loss of heterozygosity\n- 8 patients (33.3%) had chromosome 6 copy loss","methodology":"Cross-sectional integrative genomic analysis using whole-exome sequencing (paired tumor-normal) and RNAseq from 24 cancer patients; four HLA typing tools used; somatic mutations, loss of heterozygosity, and chromosome copy number analyzed.","limitations":"Very small sample size (n=24) limits generalizability. Cross-sectional design cannot determine causality. Only HLA class I was assessed—HLA class II disruption was not analyzed. Different cancer types were pooled together."},{"rthcId":"RPEP-12915","title":"Multimodal Prehabilitation for Hernia Repair: Linking Metabolic Modulation and Mechanical Methods.","authors":"Paduraru, Dan Nicolae; Palcau, Alexandru Cosmin; Ion, Daniel; Seicaru, Razvan","year":2025,"journal":"Biomedicines, 13(12)","doi":"10.3390/biomedicines13123117","pmid":"41463126","tags":["glp-1","weight-loss","side-effects","collagen-peptides"],"studyType":"narrative-review","evidenceStrength":"moderate","keyFinding":"GLP-1 receptor agonists achieve 10–20% weight reduction and reduce perioperative complications in hernia patients, but the delayed gastric emptying they cause creates anesthesia safety challenges requiring individualized fasting protocols.","whyItMatters":"Hernia surgery in obese and diabetic patients has high complication rates that inflate healthcare costs and patient suffering. Preoperative optimization with GLP-1 drugs could make surgery safer and reduce recurrence—but only if gastric emptying risks are properly managed.","specificNumbers":"- 20+ million hernia repairs performed annually worldwide\n- GLP-1 drugs produced 10-20% weight reduction preoperatively\n- GRIP/CRIP approach: 5-7% five-year recurrence vs 15% conventional\n- Reduced surgical site infections, thromboembolic events, and wound dehiscence with GLP-1 pretreatment","methodology":"Comprehensive narrative review incorporating recent clinical trials, observational studies, and meta-analyses on GLP-1 drugs, botulinum toxin A, progressive pneumoperitoneum, and biomechanical repair for hernia surgery.","limitations":"Narrative review subject to selection bias. No randomized trials specifically on GLP-1 drugs as hernia surgery prehabilitation. Optimal timing for stopping GLP-1 drugs before surgery is not established. Evidence on long-term hernia recurrence with preoperative GLP-1 use is lacking."},{"rthcId":"RPEP-12916","title":"Anticandidal Activity of Lipopeptides Containing an LL-37-Derived Peptide Fragment KR12.","authors":"Paduszynska, Malgorzata Anna; Neubauer, Damian; Kamysz, Wojciech; Kamysz, Elzbieta","year":2025,"journal":"Molecules (Basel, Switzerland), 30(7)","doi":"10.3390/molecules30071598","pmid":"40286204","tags":["ll-37","antimicrobial-peptides","peptide-design","infection"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Five lipidated derivatives of KR12 (C10, C12, C14, 2-butyloctanoic acid, and 4-phenylbenzoic acid variants) showed strong antifungal activity against planktonic Candida cells, and C14-KR12-NH2 additionally disrupted Candida albicans biofilms—a notoriously drug-resistant state.","whyItMatters":"Candida infections kill hundreds of thousands of immunocompromised patients globally each year, and resistance to available antifungals is rising. Biofilm-forming Candida is particularly lethal and difficult to treat. A short, modifiable human-derived peptide fragment offers a novel, potentially resistance-resistant therapeutic approach.","specificNumbers":"- 24 lipopeptide derivatives synthesized from KR12\n- 5 highly active against planktonic Candida cells\n- C14-KR12-NH2 active against C. albicans biofilms at 24, 48, and 72 hours\n- 4 Candida species tested: C. albicans, C. glabrata, C. tropicalis, C. lipolytica","methodology":"In vitro study synthesizing KR12-NH2 amide and 24 lipidated derivatives via fatty acid substitution; tested against Candida albicans, C. glabrata, C. tropicalis, and C. lipolytica; antifungal activity assessed for planktonic cells and biofilm cultures at 24/48/72 hours.","limitations":"In vitro only—no animal model testing of antifungal efficacy or safety. Cytotoxicity to human cells was not fully characterized for all derivatives. Optimal lipid chain length may vary across Candida species. Biofilm results limited to C. albicans."},{"rthcId":"RPEP-12917","title":"Systemic Cancer Hallmarks as Novel Markers Associated with Progression-Free Survival in Gastroenteropancreatic Neuroendocrine Tumor Patients Undergoing Peptide Receptor Radionuclide Therapy.","authors":"Padwal, Mahesh Kumar; Parghane, Rahul Vithalrao; Chakraborty, Avik; Ujaoney, Aman Kumar; Anaganti, Narasimha; Basu, Sandip; Basu, Bhakti","year":2025,"journal":"Neuroendocrinology, 115(12), 910-923","doi":"10.1159/000542918","pmid":"39626642","tags":["cancer","peptide-delivery","receptor-signaling"],"studyType":"prospective-cohort","evidenceStrength":"moderate","keyFinding":"Systemic cancer hallmark gene signatures in peripheral blood were significantly associated with progression-free survival in PRRT-treated GEP-NET patients, with cell cycle and immune-related pathways showing the strongest predictive value.","whyItMatters":"PRRT is a key peptide-based treatment for advanced neuroendocrine tumors, but predicting who will benefit most remains difficult. Blood-based biomarkers could enable personalized treatment decisions without invasive biopsies.","specificNumbers":"- Discovery cohort: 59 GEP-NET patients + 38 healthy controls\n- Evaluation cohort: 66 GEP-NET patients\n- 30 cancer hallmarks differentially enriched in patients vs controls\n- 2 hallmarks (heme metabolism, IL2/STAT5) independently predicted PFS in both cohorts (p<0.05)","methodology":"Prospective cohort study using RNA-Seq on peripheral blood from a discovery cohort (59 PRRT-naïve GEP-NET patients + 38 healthy controls) and an independent evaluation cohort (66 GEP-NET patients). Cancer hallmark gene set enrichment was correlated with progression-free survival.","limitations":"Relatively small cohort sizes; single-center study design; RNA-Seq from peripheral blood may not fully reflect tumor biology; requires prospective validation before clinical implementation."},{"rthcId":"RPEP-12918","title":"Antinociceptive and neuromodulatory effects of the scorpion venom tetrapeptide tetrascorpin-1 in a long-lasting pain hypersensitivity model in mice.","authors":"Pagano, Salvatore; Limongelli, Rebecca; Moslah, Wassim; Saada, Mohamed-Chiheb; Manzo, Iolanda; Bonsale, Roozbe; Teweldemedhin, Milena Melake; Fusco, Antimo; Guida, Francesca; Belardo, Carmela; Morace, Andrea Maria; Perrone, Michela; Ricciardi, Federica; Pierretti, Gorizio; Vastarella, Maria Giovanna; Infantino, Rosmara; Srairi-Abid, Najet; Maione, Sabatino; Palazzo, Enza; Luongo, Livio","year":2025,"journal":"Toxicon : official journal of the International Society on Toxinology, 268, 108611","doi":"10.1016/j.toxicon.2025.108611","pmid":"41061805","tags":["venom-peptides","pain","neuropeptides","nasal-peptides","inflammation"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Intranasal AaTs-1 significantly reduced pain hypersensitivity and neuroinflammation while preventing morpho-functional alterations in spinal cord neurons and glial cells in a formalin-induced chronic pain model.","whyItMatters":"Chronic pain remains poorly managed, and venom-derived peptides represent a novel therapeutic avenue. The intranasal delivery route is particularly promising as it bypasses the blood-brain barrier, potentially offering a non-invasive way to deliver peptide therapeutics to the central nervous system.","specificNumbers":"- AaTs-1 is a tetrapeptide (4 amino acids) from Androctonus australis scorpion venom\n- Administered intranasally for 10 days\n- Abolished mechanical allodynia and thermal hyperalgesia\n- Reversed hyperactivation of spinal nociceptive-specific neurons\n- Partially restored spinal cytokine balance and glial cell phenotypes","methodology":"Animal study using formalin-induced long-lasting pain hypersensitivity in mice. AaTs-1 was administered intranasally daily for 10 days. Assessed pain responses, cytokine levels, and neuronal/glial changes in the spinal cord.","limitations":"Animal study only — effects in humans unknown; formalin model may not fully represent clinical chronic pain conditions; long-term safety of repeated intranasal peptide delivery not assessed; mechanism of action through FPR-2 needs further confirmation in vivo."},{"rthcId":"RPEP-12919","title":"Assessment of Gastric Content Using Gastric Ultrasound in Patients on Glucagon-Like Peptide-1 Receptor Agonists Before Anesthesia.","authors":"Pai, Sher-Lu; Nimma, Sindhuja R; Beam, W Brian; VanderWielen, Beth A; Kalagara, Hari K; Bettini, Layne M; Yu, Soojie; Sharpe, Emily E; Harbell, Monica W","year":2025,"journal":"Anesthesia and analgesia","doi":"10.1213/ANE.0000000000007764","pmid":"41032460","tags":["glp-1","side-effects","peptide-safety"],"studyType":"prospective-cohort","evidenceStrength":"moderate","keyFinding":"A substantial proportion of patients on GLP-1 receptor agonists had high residual gastric contents before anesthesia despite standard fasting, suggesting current preoperative fasting guidelines may be inadequate for this population.","whyItMatters":"With millions now taking GLP-1 drugs for diabetes and weight loss, the surgical safety implications are enormous. Delayed gastric emptying increases the risk of pulmonary aspiration during anesthesia — a potentially life-threatening complication.","specificNumbers":"- 316 patients studied; 35.8% had high residual gastric contents\n- Weekly injection withholding: 8 days (low RGC) vs 6 days (high RGC), p=0.003\n- Cutoff: 7.5 days of withholding weekly injections\n- Solid food fasting: 20 hours (low RGC) vs 15 hours (high RGC), p<0.001\n- Cutoff: 21.3 hours fasting from solids\n- Opioid use: 5.3% (high RGC) vs 1.0% (low RGC), p=0.027","methodology":"Prospective cohort study across 3 hospitals. Adult patients taking GLP-1 RAs and scheduled for anesthesia underwent preoperative gastric ultrasound to assess residual gastric contents (RGC). Preoperative factors associated with high RGC were evaluated.","limitations":"Sample size and specific prevalence numbers not provided in abstract; ultrasound assessment is operator-dependent; did not directly measure aspiration events, only risk indicators; may not account for all GLP-1 RA types and doses."},{"rthcId":"RPEP-12920","title":"GLP-1 Receptor Agonist Induced Eustachian Tube Dysfunction: Database and Systematic Review of Otolaryngologic Adverse Events.","authors":"Pak, Kaitlynne Y; Cutri, Raffaello M; Nadeem, Wasiq; Kothari, Dhruv; Wong, Yu-Tung; Wu, Arthur W; Miller, Mia E","year":2025,"journal":"Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology, 46(1), 19-22","doi":"10.1097/MAO.0000000000004373","pmid":"39666743","tags":["glp-1","semaglutide","side-effects","weight-loss"],"studyType":"case-report","evidenceStrength":"preliminary","keyFinding":"GLP-1 receptor agonists were associated with eustachian tube dysfunction, particularly the patulous variant, likely caused by rapid loss of soft tissue bulk around the eustachian tube opening.","whyItMatters":"As GLP-1 drugs become widely used for weight loss, clinicians need to recognize ear symptoms as a potential side effect. Eustachian tube dysfunction can significantly impact quality of life, and early recognition may lead to better management.","specificNumbers":"- 97,237 total GLP-1 adverse events in FAERS\n- 958 (0.99%) were ear-related\n- Exenatide: highest proportion of ear AEs (1.52%)\n- Semaglutide: 1.17% ear AEs\n- Liraglutide: 1.16% ear AEs\n- Dulaglutide: 417 total ear AEs (highest count)\n- Systematic review: 937 articles screened, 10 met criteria","methodology":"Combined case report, FDA Adverse Event Reporting System (FAERS) database analysis, and PRISMA-guided systematic literature review examining otolaryngologic adverse events of GLP-1 RAs.","limitations":"Case reports and database analysis cannot establish causation; FAERS data is subject to reporting bias; small number of documented cases; unclear incidence rate in the broader GLP-1 RA population."},{"rthcId":"RPEP-12921","title":"Stapled Peptides as Inhibitors of mRNA Deadenylation.","authors":"Pal, Sunit; Gordijenko, Ilja; Schmeing, Stefan; Biswas, Somarghya; Akbulut, Yasemin; Gasper, Raphael; 't Hart, Peter","year":2025,"journal":"Angewandte Chemie (International ed. in English), 64(1), e202413911","doi":"10.1002/anie.202413911","pmid":"39319385","tags":["cyclic-peptides","peptide-design"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Stapled peptides successfully inhibited mRNA deadenylation by disrupting the NOT9 subunit of the CCR4-NOT complex, establishing a new strategy for preserving beneficial mRNA stability and translational activity.","whyItMatters":"While mRNA therapies have focused on silencing harmful genes, this is one of the first approaches to do the opposite — protect beneficial mRNA. Stapled peptides offer structural stability that regular peptides lack, making them viable drug candidates for this novel mechanism.","specificNumbers":"- NIP-2 binding affinity: KD = 60.4 nM\n- RNA binding inhibition: IC50 = 333 nM\n- Cell permeability: EC50 = 2.44 microM (NIP-2), 0.34 microM (optimized NIP-2-H27A-N3)\n- Intracellular mRNA stabilization demonstrated at 100 microM in HeLa cells\n- 7-fold improvement in cell permeability with optimization","methodology":"In vitro study involving rational design and synthesis of stapled peptides targeting the NOT9 subunit of the CCR4-NOT deadenylation complex, followed by biochemical and functional assays to assess mRNA stabilization.","limitations":"In vitro study only — no in vivo or cellular data presented in abstract; selectivity for specific mRNA transcripts not demonstrated; pharmacokinetic properties of the stapled peptides unknown; far from clinical application."},{"rthcId":"RPEP-12922","title":"Selective Receptor Modulation by Truncated Neuropeptide Y (3-36) Dissociates Vasoconstriction from Neuroprotection in Experimental Glaucoma.","authors":"Palanivel, Viswanthram; Basavarajappa, Devaraj; Salkar, Akanksha; Komáromy, András M; Tietz, Ole; Eva, Taslima Akter; Chitranshi, Nitin; Mirzaei, Mehdi; Gupta, Veer; You, Yuyi; Graham, Stuart L; Gupta, Vivek","year":2025,"journal":"Molecular neurobiology, 63(1), 334","doi":"10.1007/s12035-025-05636-4","pmid":"41460555","tags":["neuropeptides","eye-health","neuroprotection"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Truncated NPY (3-36) selectively activated neuroprotective pathways (via Y2/Y5 receptors) while avoiding vasoconstriction (mediated by Y1 receptors), demonstrating that receptor-selective peptide analogs can dissociate beneficial from harmful effects in glaucoma treatment.","whyItMatters":"Glaucoma is a leading cause of blindness, and neuroprotection of retinal ganglion cells is a major unmet need. This study shows that peptide modification can eliminate dangerous side effects while preserving therapeutic benefit, advancing NPY-based therapies toward clinical viability.","specificNumbers":"- NPY(1-36): caused transient vasoconstriction via Y1 receptor\n- NPY(3-36): no vasoconstriction; selectively activates Y2 and Y5 receptors\n- NPY(3-36) preserved retinal ganglion cell density under elevated IOP\n- Reduced astrocytic and microglial activation","methodology":"Animal study in mice using fluorescein angiography to assess retinal vascular responses after intravitreal injection of NPY analogs, followed by evaluation of neuroprotective effects in an experimental glaucoma model.","limitations":"Animal study only — mouse retinal physiology may differ from human; intravitreal injection is invasive; long-term safety and efficacy of repeated NPY (3-36) dosing not established; glaucoma models may not fully replicate human disease."},{"rthcId":"RPEP-12923","title":"Real-World Analysis of Short-Term Effectiveness of Oral Semaglutide: Impact on Glycometabolic Control and Cardiovascular Risk.","authors":"Palazzi, Sara; Sentinelli, Federica; Zugaro, Antonella; Morgante, Sara; Santarelli, Livia; Melanzi, Sandra; De Mutiis, Annamaria; Piersanti, Deamaria; Macerola, Barbara; Iezzi, Marco; Mercuri, Pietro; Ferranti, Alessandro; Tienforti, Daniele; Cavallo, Maria Gisella; Barbonetti, Arcangelo; Baroni, Marco Giorgio","year":2025,"journal":"Pharmaceuticals (Basel, Switzerland), 18(6)","doi":"10.3390/ph18060856","pmid":"40573252","tags":["semaglutide","diabetes","cardiovascular","oral-peptides"],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"Oral semaglutide produced significant short-term reductions in HbA1c and body weight, along with improvements in cardiovascular risk markers, in a real-world type 2 diabetes population.","whyItMatters":"Most semaglutide data comes from controlled clinical trials with strict inclusion criteria. This real-world study confirms that the benefits translate to everyday clinical practice, and that even the oral formulation — not just injections — delivers meaningful results quickly.","specificNumbers":"- 167 patients; mean age 66.5 years; baseline HbA1c 8.4%\n- 83.2% on 7 mg dose\n- HbA1c: 8.4% to 7.1% (-1.3%) in 3 months\n- 30.5% lost more than 5% body weight (largest HbA1c drop: -1.9%)\n- Significant cardiovascular risk reduction (p=0.04)\n- Significant lipid parameter improvements","methodology":"Multi-center real-world observational study across 4 Italian diabetes centers. Patients newly prescribed oral semaglutide were assessed at baseline and 3 months for glycemic control, weight, and cardiovascular risk parameters.","limitations":"Observational design without a control group; 3-month timeframe limits long-term conclusions; Italian patient population may not generalize globally; specific effect sizes not provided in abstract."},{"rthcId":"RPEP-12924","title":"Chronic Tendinopathy Driven by Neoinnervation: The Role of the Paratenon, Upregulated Neural Biomarkers, and Evolving Evidence - A Scoping Review.","authors":"Palee, Suwannika; Jarusriwanna, Atthakorn; Lee, Danielle; Yener, Ugur; Kaye, Alan D; Shaparin, Naum; Wahezi, Sayed E","year":2025,"journal":"Pain physician, 28(4), 287-297","doi":null,"pmid":"40773634","tags":["neuropeptides","pain","muscle-recovery"],"studyType":"scoping-review","evidenceStrength":"moderate","keyFinding":"Neuropeptides including substance P and CGRP are consistently upregulated in chronic tendinopathy, with the paratenon serving as a key source of neoinnervation that drives ongoing pain signaling.","whyItMatters":"Chronic tendon pain affects millions and often responds poorly to treatment. Understanding that new nerve growth — mediated by specific neuropeptides — drives pain opens the door to targeted therapies that address the root cause rather than just masking symptoms.","specificNumbers":"- 26 studies reviewed\n- 73% (19/26) found neoinnervation in chronic tendinopathy\n- 76.9% (20/26) highlighted paratenon role\n- 53.8% (14/26) examined both neoinnervation and paratenon\n- PGP 9.5 upregulated in 57.6% of studies\n- Substance P upregulated in 50% of studies","methodology":"Scoping review following systematic methodology. Analyzed frequency and progression of neural biomarker upregulation across studies of chronic tendinopathy, with focus on the paratenon's role in neoinnervation.","limitations":"Scoping review methodology is less rigorous than systematic review with meta-analysis; heterogeneity across included studies in methods and biomarker measurement; mostly observational data without clear causal mechanisms; limited treatment outcome data."},{"rthcId":"RPEP-12925","title":"Lymph node-targeted, mKRAS-specific amphiphile vaccine in pancreatic and colorectal cancer: phase 1 AMPLIFY-201 trial final results.","authors":"Palmer, Chrisann D; Rappaport, Aaron R; Klempner, Samuel J","year":2025,"journal":"Nature medicine","doi":"10.1038/s41591-025-03876-4","pmid":"40790272","tags":["cancer-research"],"studyType":"human-phase-1","evidenceStrength":"moderate","keyFinding":"At 19.7 months follow-up, high T cell responders to ELI-002 2P had not reached median RFS or OS, vs 3.02 months RFS and 15.98 months OS in low responders. Antigen spreading in 67%. No grade 3+ AEs.","whyItMatters":"Long-term follow-up confirms that robust T cell responses to KRAS vaccines correlate with dramatically improved survival in pancreatic/colorectal cancer.","specificNumbers":"19.7 months follow-up; RFS HR 0.12 P=0.0002; OS HR 0.23 P=0.0099; antigen spreading 67%","methodology":"Extended follow-up of phase 1 AMPLIFY-201. T cell response threshold 9.17-fold over baseline.","limitations":"Phase 1, no randomization, self-selected high/low responder groups."},{"rthcId":"RPEP-12926","title":"AhR Activation Transcriptionally Induces Anti-Microbial Peptide Alpha-Defensin 1 Leading to Reversal of Gut Microbiota Dysbiosis and Colitis.","authors":"Palrasu, Manikandan; Kakar, Khadija; Marudamuthu, Amarnath; Hamida, Hamida; Thada, Shruthi; Zhong, Yin; Staley, Shanieka; Busbee, Philip Brandon; Li, Jie; Garcia-Buitrago, Monica; Nagarkatti, Mitzi; Nagarkatti, Prakash","year":2025,"journal":"Gut microbes, 17(1), 2460538","doi":"10.1080/19490976.2025.2460538","pmid":"39894796","tags":["antimicrobial-peptides","gut-healing","inflammation","immune-function"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"AhR transcriptionally induces alpha-defensin 1 expression, and this induction reverses gut microbiota dysbiosis and attenuates colitis, establishing a direct mechanistic link between environmental sensing, antimicrobial peptide production, and intestinal health.","whyItMatters":"Alpha-defensin 1 is a critical first-line defense peptide in the gut. Demonstrating that it can be upregulated through AhR — a receptor responsive to dietary and environmental signals — provides a tangible therapeutic strategy for restoring gut health in inflammatory bowel disease.","specificNumbers":"- Positive correlation between AhR and alpha-defensin 1 in CD patients and mouse models\n- AhR targets DRE3 on the alpha-defensin 1 promoter\n- AhR activation reversed dysbiosis and alleviated colitis in mice","methodology":"Animal study examining the AhR–alpha-defensin 1 axis using gene expression analysis, transcriptional regulation studies, gut microbiome profiling, and colitis models to establish the mechanistic pathway.","limitations":"Animal model findings may not directly translate to humans; other AhR downstream effects could confound results; specific AhR ligands for therapeutic use not optimized; alpha-defensin 1 may behave differently in the human colon versus small intestine."},{"rthcId":"RPEP-12927","title":"AhR-Dependent Induction of β-Defensin 1 in Colonic Epithelial Cells Regulates Cross-Talk between Gut Microbiota and Immune Response Leading to Attenuation of Colitis.","authors":"Palrasu, Manikandan; Marudamuthu, Amarnath; Kakar, Khadija; Hamida, Hamida; Thada, Shruthi; Gupta, Rohan; Wilson, Kiesha; Carter, Taylor; Zhong, Yin; Saxena, Archana; Yang, Xiaoming; Singh, Narendra; Busbee, Philip Brandon; Li, Jie; Garcia-Buitrago, Monica; Nagarkatti, Prakash; Nagarkatti, Mitzi","year":2025,"journal":"Advanced science (Weinheim, Baden-Wurttemberg, Germany), 12(25), e2416324","doi":"10.1002/advs.202416324","pmid":"40410944","tags":["antimicrobial-peptides","gut-healing","inflammation","immune-function"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"AhR activation induced β-defensin 1 expression in colonic epithelial cells, which regulated gut microbiota composition and immune cross-talk to attenuate colitis in both human tissue samples and three mouse colitis models.","whyItMatters":"Antimicrobial peptides are the body's frontline defense against gut pathogens. Showing that a natural receptor can be activated by dietary compounds to boost these peptides opens a potential therapeutic strategy for inflammatory bowel disease that works with the body's own defense systems.","specificNumbers":"- BD-1 decreased in both UC and CD patients and in 3 mouse colitis models\n- AhR ligands induced BD-1 through 2 dioxin-responsive elements on the promoter\n- Blocking BD-1 with antibodies abolished the protective effect\n- IEC-specific AhR deletion prevented BD-1 induction and colitis protection","methodology":"Combined human and animal study. Analyzed β-defensin 1 expression in UC and CD patient tissue. Tested AhR ligands (dietary and environmental) in three mouse colitis models. Assessed microbiota changes and immune cell responses.","limitations":"Mouse colitis models may not fully replicate human IBD; AhR activation has broad effects beyond defensin induction; long-term safety of AhR ligand supplementation unknown; specific dietary compounds and doses for clinical benefit not established."},{"rthcId":"RPEP-12928","title":"In Situ Vaccination with a Vpr-Derived Peptide Elicits Systemic Antitumor Immunity by Improving Tumor Immunogenicity.","authors":"Pan, Danjie; Du, Ling; Liu, Jiayang; Kuerban, Kudelaidi; Huang, Xuan; Wang, Yue; Guo, Qiuyu; Chen, Huaning; Wang, Songna; Wang, Li; Zhou, Pinghong; Meng, Zhefeng; Ye, Li","year":2025,"journal":"Vaccines, 13(7)","doi":"10.3390/vaccines13070710","pmid":"40733687","tags":["cancer","immune-function","peptide-design","cell-penetrating"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Intratumoral injection of a Vpr-derived peptide improved tumor immunogenicity by releasing whole-tumor antigens, eliciting systemic anti-tumor immune responses that targeted both local and distant tumors.","whyItMatters":"Traditional cancer vaccines require identifying specific tumor antigens, which is expensive and tumor-specific. This peptide-based approach turns the patient's own tumor into the vaccine source, potentially making cancer vaccination universally applicable without prior antigen identification.","specificNumbers":"- 4 Vpr peptides designed; P1 and P4 showed cytotoxicity\n- P1 induced apoptosis and immunogenic cell death (CRT, ATP, HMGB1)\n- In situ P1 vaccination inhibited both local and distant tumors\n- P1 + CD47 inhibitor enhanced distant tumor suppression\n- Activated DCs, T cells, and macrophages","methodology":"Animal study testing intratumoral injection of Vpr-derived peptides in tumor-bearing mice. Assessed local and systemic immune responses, tumor regression, and the abscopal effect on distant tumors.","limitations":"Animal study only — mouse immune systems differ significantly from human; the abscopal effect is notoriously difficult to reproduce clinically; safety of Vpr-derived peptides in humans needs evaluation; tumor heterogeneity may limit effectiveness."},{"rthcId":"RPEP-12929","title":"Glucose-dependent insulinotropic peptide (GIP) suppresses androgen biosynthesis in PCOS mouse models and cellular systems.","authors":"Pan, Mengru; Qian, Yifan; Jiang, Linlin; Cao, Chunwei; Li, Lin","year":2025,"journal":"Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology, 41(1), 2582506","doi":"10.1080/09513590.2025.2582506","pmid":"41249890","tags":["tirzepatide","fertility","hormone-optimization","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"GIP significantly reduced testosterone secretion in PCOS mouse models and NCI-H295R cells, suppressing androgen biosynthesis through specific molecular pathways identified via RNA sequencing.","whyItMatters":"PCOS affects up to 13% of women of reproductive age, and hyperandrogenism is its most distressing feature. Current anti-androgen treatments have significant limitations. GIP-based therapies could offer a new approach, especially given the growing availability of GIP-containing drugs like tirzepatide.","specificNumbers":"- GIP significantly reduced testosterone in PCOS mice\n- Downregulated GIPR, STAR, CYP11A1, and CYP17A1 in ovarian cells\n- PSENEN was the most downregulated gene on RNA-seq\n- PSENEN knockdown further reduced testosterone production","methodology":"Combined in vivo (DHEA-induced PCOS mouse model) and in vitro (NCI-H295R adrenal cell line) study using CCK8, flow cytometry, RT-qPCR, Western blot, ELISA, and RNA-seq to assess GIP's effects on androgen synthesis.","limitations":"Animal model — DHEA-induced PCOS may not fully represent human PCOS pathophysiology; NCI-H295R cells are an adrenal cancer cell line, not normal ovarian tissue; dose-response relationships not fully characterized; no human clinical data."},{"rthcId":"RPEP-12930","title":"Dual-phase exenatide delivery system: PLGA nanoparticles embedded in thermosensitive PLGA-PEG-PLGA hydrogel for sustained glycemic control.","authors":"Pan, Shu; Dong, Nan; Yuan, Haoyang; Zhang, Yu; He, Haibing; Yin, Tian; Wang, Yanjiao; Gou, Jingxin; Tang, Xing","year":2025,"journal":"Expert opinion on drug delivery, 22(12), 2001-2015","doi":"10.1080/17425247.2025.2564870","pmid":"40977331","tags":["exenatide","glp-1","peptide-delivery","bioavailability"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"The biphasic delivery system (Ex-NPs-gel) provided both rapid initial and sustained long-term exenatide release, achieving prolonged glycemic control compared to standard exenatide injections in diabetic rats.","whyItMatters":"Poor patient compliance due to frequent injections is a major barrier for GLP-1 agonist therapy. A single injection that provides weeks of drug release could dramatically improve treatment adherence and outcomes for millions of diabetes patients.","specificNumbers":"- Sustained release over 31 days in vitro\n- Initial burst release below 9% in first 24 hours\n- Single injection stabilized blood glucose for 15+ days in diabetic rats\n- Restored hepatic and pancreatic functions","methodology":"Animal study developing and testing PLGA nanoparticles loaded with exenatide, embedded in PLGA-PEG-PLGA thermosensitive hydrogel. Characterized particle properties and release kinetics, then tested in vivo glycemic control in diabetic rat models.","limitations":"Animal study only — rat pharmacokinetics differ from human; long-term biocompatibility of implanted hydrogel needs assessment; manufacturing scalability and cost not addressed; comparison with existing long-acting formulations (weekly semaglutide) not performed."},{"rthcId":"RPEP-12931","title":"Semaglutide attenuates lipotoxicity-induced cardiac injury by inhibiting Slc27a2 expression.","authors":"Pan, Xiaoyu; Wang, Shuqi; Yang, Xiaoman; Jia, Boying; Chen, Shuchun","year":2025,"journal":"Chemico-biological interactions, 418, 111583","doi":"10.1016/j.cbi.2025.111583","pmid":"40456371","tags":["semaglutide","cardiovascular","receptor-signaling"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"Semaglutide downregulated Slc27a2/FATP2 expression on cardiomyocytes, reducing lipotoxic fat accumulation and protecting against inflammation, oxidative stress, impaired cardiac function, and apoptosis in an obesity model.","whyItMatters":"Semaglutide's cardiovascular benefits have been demonstrated in major clinical trials, but the exact mechanisms have been unclear. This study identifies a specific pathway — fat transport protein inhibition — that explains how semaglutide protects the heart, potentially enabling more targeted cardioprotective therapies.","specificNumbers":"- High-fat diet increased Slc27a2 on cardiomyocyte membranes\n- Semaglutide reversed cardiac dysfunction and reduced Slc27a2\n- A2A antagonist partially blocked semaglutide's protection\n- A2A agonist enhanced semaglutide's protection","methodology":"Animal study using high-fat diet mouse models. Assessed FATP2 expression, lipid deposition, inflammatory markers, oxidative stress, cardiac function, and cardiomyocyte viability with and without semaglutide treatment.","limitations":"Animal study — mouse cardiac metabolism may differ from human; single mechanism studied while semaglutide likely has multiple cardioprotective pathways; dose and timing may not translate directly to human dosing; did not assess whether effects persist after drug discontinuation."},{"rthcId":"RPEP-12932","title":"Versatile Biomaterial Additive: A Game-Changing Multifunctional Synthetic Peptide With Pro-Regenerative, Anti-Inflammatory, and Antibacterial Properties.","authors":"Panasiuk, Mirosława; Chraniuk, Milena; Bollin, Piotr; Sawicka, Justyna; Sylla, Anna; Hovhannisyan, Lilit; Biernat, Monika; Rodziewicz-Motowidło, Sylwia; Gromadzka, Beata","year":2025,"journal":"Journal of biomedical materials research. Part B, Applied biomaterials, 113(5), e35591","doi":"10.1002/jbm.b.35591","pmid":"40321101","tags":["antimicrobial-peptides","wound-healing","bone-joint","peptide-design","inflammation"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"The synthetic peptide exhibited triple functionality — pro-regenerative, anti-inflammatory, and antibacterial — when used as an additive in bone tissue engineering biomaterials, offering a comprehensive approach to bone repair.","whyItMatters":"Bone injuries often face three simultaneous challenges: slow healing, infection risk, and excessive inflammation. A single peptide addressing all three could simplify treatment, reduce costs, and improve outcomes compared to current multi-drug approaches.","specificNumbers":"- Cell proliferation: over 200% of control with CH-UG46 scaffolds\n- Bacterial growth inhibition: over 83% for all strains tested\n- A. baumannii reduction: 99.86%\n- Working concentration: 40-80 microg/mL\n- No cytotoxicity to osteoblasts or fibroblasts","methodology":"In vitro study involving peptide synthesis, characterization, and testing as a biomaterial additive. Assessed regenerative capacity, anti-inflammatory effects, and antibacterial activity in polymer scaffold and biocomposite systems.","limitations":"In vitro study only — in vivo performance may differ significantly; long-term stability of the peptide in biomaterial matrices not assessed; cost and manufacturing scalability unknown; comparison with existing standard-of-care treatments not performed."},{"rthcId":"RPEP-12933","title":"A comprehensive review on liraglutide and novel nanocarrier-based systems for the effective delivery of liraglutide.","authors":"Pandey, Ajay; Rath, Goutam; Chawala, Ruchi; Goyal, Amit Kumar","year":2025,"journal":"Naunyn-Schmiedeberg's archives of pharmacology, 398(7), 8241-8258","doi":"10.1007/s00210-025-03918-1","pmid":"40014122","tags":["liraglutide","peptide-delivery","bioavailability","glp-1"],"studyType":"narrative-review","evidenceStrength":"preliminary","keyFinding":"Multiple nanocarrier platforms (polymeric, lipid-based, and hybrid systems) have demonstrated improved liraglutide stability, protection from degradation, and enhanced bioavailability in preclinical studies.","whyItMatters":"Liraglutide requires daily injections, which limits patient compliance and quality of life. Nanocarrier technologies could enable oral delivery or less frequent dosing, making this important medication more accessible and convenient for millions of patients.","specificNumbers":"- No specific efficacy numbers reported\n- Six nanocarrier platforms reviewed: nanofibers, liposomes, polymeric NPs, exosomes, hydrogels, lipid NPs","methodology":"Narrative review surveying the scientific literature on liraglutide pharmacology, delivery challenges, and novel nanocarrier-based systems including their mechanisms, advantages, and preclinical performance.","limitations":"Review article — synthesizes existing literature but generates no new data; most nanocarrier studies are preclinical with limited human data; manufacturing scalability and cost remain significant barriers; regulatory pathway for nano-formulated peptides is complex."},{"rthcId":"RPEP-12934","title":"Effects of semaglutide in obesity-related heart failure with preserved ejection fraction across the age spectrum: Findings from the STEP-HFpEF programme.","authors":"Pandey, Ambarish; Moroney, Michael; Verma, Subodh; Borlaug, Barry A; Butler, Javed; Davies, Melanie J; Kitzman, Dalane W; Shah, Sanjiv J; Petrie, Mark C; Rönnbäck, Cecilia; Domdey, Anne; Rasmussen, Søren; Chinnakondepalli, Khaja M; Patel, Shachi; Kosiborod, Mikhail N","year":2025,"journal":"European journal of heart failure, 27(11), 2537-2543","doi":"10.1002/ejhf.70049","pmid":"41290376","tags":["semaglutide","glp1-receptor-agonists","heart-failure","obesity-weight-management","aging-longevity"],"studyType":"secondary-analysis","evidenceStrength":"strong","keyFinding":"CKD doubled heart failure event rates, but tirzepatide benefits were consistent across kidney function levels. Creatinine-based and cystatin C-based eGFR gave discordant results.","whyItMatters":"Many HFpEF patients have CKD, and understanding drug-kidney interactions is essential for safe prescribing.","specificNumbers":"Of 1,145 participants: 8.8% under 55, 23.3% aged 55-64, 42.4% aged 65-74, 25.5% aged 75+. KCCQ-CSS interaction P = 0.80. Body weight interaction P not significant. Treatment: 52 weeks.","methodology":"Pre-specified analysis of the SUMMIT double-blind RCT with 731 patients enriched for CKD.","limitations":"Sub-analysis of SUMMIT; not powered for CKD subgroup outcomes. Short-term renal function data."},{"rthcId":"RPEP-12935","title":"Frailty and Effects of Semaglutide in Obesity-Related HFpEF: Findings From the STEP-HFpEF Program.","authors":"Pandey, Ambarish; Kitzman, Dalane W; Chinnakondepalli, Khaja M; Patel, Shachi; Borlaug, Barry A; Butler, Javed; Davies, Melanie J; Shah, Sanjiv J; Verma, Subodh; Rönnbäck, Cecilia; Domdey, Anne; Liisberg, Karoline; Schou, Morten; Perna, Eduardo; Ahmed, Fozia Z; Fu, Michael; Petrie, Mark C; Kosiborod, Mikhail N","year":2025,"journal":"JACC. Heart failure, 13(10), 102610","doi":"10.1016/j.jchf.2025.102610","pmid":"40956259","tags":["semaglutide","glp1-receptor-agonists","heart-failure","obesity-weight-management","aging-longevity"],"studyType":"secondary-analysis","evidenceStrength":"strong","keyFinding":"Semaglutide's efficacy in obesity-related HFpEF was consistent across frailty subgroups, and semaglutide treatment itself improved frailty status — a novel and clinically significant finding.","whyItMatters":"Frailty is extremely common in HFpEF and is associated with worse outcomes. Clinicians often hesitate to use weight loss drugs in frail patients, fearing they might worsen frailty. This study shows semaglutide is not only safe but actually beneficial across the frailty spectrum.","specificNumbers":"Of 1,145 participants, 60.4% were most frail, 30.0% more frail, 9.6% nonfrail. Weight loss was similar across groups (P-interaction = 0.38). Treatment lasted 52 weeks with semaglutide 2.4 mg once weekly.","methodology":"Secondary analysis of the STEP-HFpEF randomized controlled trial program. Participants were stratified by baseline frailty status, and semaglutide's effects on HF symptoms, physical limitations, body weight, and frailty scores were assessed across subgroups.","limitations":"Secondary analysis of existing trial data; frailty assessment tools may not capture all dimensions of frailty; trial participants may not represent the most frail patients seen in clinical practice; mechanisms behind frailty improvement not elucidated."},{"rthcId":"RPEP-12936","title":"Efficacy and Safety of Orforglipron in Obese Adults With or Without Diabetes: A Systematic Review and Meta-Analysis.","authors":"Pandey, Ravi Kumar; Jan, Mahnoor; Mohammad, Aqsa; Jawaid, Khawaja Arham; Naveed, Mawra; Abid, Muhammad Ali; Amir, Abdullah Bin; Ahmed, Shafique; Safiullah, Muhammad; Bhatti, Muhammad Imaz; Iftikhar, Sana; Saddique, Muhammad Nabeel; Alfalh, Widyan; Omar, Rihab Mohammed Bin; Abu Dawood, Husam","year":2025,"journal":"Endocrinology, diabetes & metabolism, 8(6), e70134","doi":"10.1002/edm2.70134","pmid":"41296780","tags":["glp1-receptor-agonists","obesity-weight-management","diabetes-glucose-metabolism","cardiovascular-health"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Meta-analysis confirmed orforglipron's efficacy for weight reduction and glycemic control in obese adults with or without T2DM, with a safety profile consistent with the GLP-1 drug class.","whyItMatters":"Orforglipron could be a game-changer: it's an oral pill that works like injectable GLP-1 drugs but without the peptide delivery challenges. Being a small molecule, it's easier and cheaper to manufacture, store, and distribute than peptide-based drugs like semaglutide.","specificNumbers":"Five RCTs with 4,410 participants. Weight loss ranged from 2.48% (3 mg) to 9.8% (45 mg). LDL-C dropped 5.34%. Triglycerides dropped 10.07%. HDL-C rose 2.94%. HbA1c dropped 0.76-1.04%. Discontinuation was highest at 24 mg (RR: 4.61).","methodology":"Systematic review and meta-analysis of randomized controlled trials identified through PubMed, Embase, Cochrane Library, and ClinicalTrials.gov through October 2025. Assessed efficacy (weight loss, HbA1c) and safety outcomes.","limitations":"Limited number of available RCTs for meta-analysis; relatively short trial durations; long-term cardiovascular and safety outcomes not yet available; comparisons with established GLP-1 RAs are indirect; publication bias possible."},{"rthcId":"RPEP-12937","title":"Peptide Receptor Radionuclide Therapy-Induced Hypercortisolemic Crisis in Ectopic Cushing Syndrome.","authors":"Pandit, Raghavendra; Yamichannaiah, Chethan; Lila, Anurag Ranjan; Karlekar, Manjiri; Memon, Saba Samad; Bandgar, Tushar","year":2025,"journal":"JCEM case reports, 3(11), luaf226","doi":"10.1210/jcemcr/luaf226","pmid":"41035789","tags":["peptide-receptor-radionuclide-therapy","neuroendocrine-tumors","hormones-endocrine"],"studyType":"case-report","evidenceStrength":"very-low","keyFinding":"PRRT triggered an acute ACTH-mediated hypercortisolemic crisis in a patient with ectopic Cushing syndrome, with cortisol reaching 141 µg/dL (normal: 5-25 µg/dL) and ACTH >2000 pg/mL, requiring emergency management.","whyItMatters":"PRRT is increasingly used for neuroendocrine tumors, but this case demonstrates that tumor lysis or stimulation during treatment can trigger dangerous hormone surges. Clinicians need to anticipate and prepare for this complication, especially in functioning tumors.","specificNumbers":"Cortisol peaked at 141 mcg/dL (reference: 5-25). ACTH exceeded 2,000 pg/mL (reference: 10-60). Patient gained 8 kg in one week. Etomidate dose: 0.02 mg/kg/h IV. Crisis occurred 5 days after first PRRT cycle.","methodology":"Case report documenting clinical presentation, biochemical findings, imaging, and management of PRRT-induced hypercortisolemic crisis.","limitations":"Single case report — cannot establish incidence or risk factors; the mechanism (tumor lysis vs. radiation-induced hormone release) is speculative; management details may not be generalizable."},{"rthcId":"RPEP-12938","title":"Efficient synthesis, stability-guided optimization and anti-ulcerative colitis evaluation of bee venom peptide melittin.","authors":"Pang, Cheng-Jian; Yao, Jing-Fang; Lv, Qiu-Lan; Zhang, Li-Ze; Yu, Qian-Yao; Zeng, Li; Qi, Yun-Kun","year":2025,"journal":"Bioorganic & medicinal chemistry letters, 128, 130357","doi":"10.1016/j.bmcl.2025.130357","pmid":"40759401","tags":["antimicrobial-peptides","inflammation-immunity","gastrointestinal-health","drug-delivery-systems"],"studyType":"animal-study","evidenceStrength":"low","keyFinding":"Stability-optimized melittin variants maintained anti-inflammatory activity while resisting protease degradation, significantly reducing ulcerative colitis severity in a mouse model.","whyItMatters":"Ulcerative colitis affects millions worldwide, and current treatments have limited efficacy and significant side effects. Bee venom peptides are a rich source of anti-inflammatory compounds, but their therapeutic development has been limited by poor stability. This study shows that chemical optimization can overcome this barrier.","specificNumbers":"PCJ-675 showed improved proteolytic stability compared to native melittin. Tested in DSS-induced ulcerative colitis mouse model. Administered orally. Reduced colon shortening and suppressed inflammation markers (TLR4/NF-kB pathway).","methodology":"Animal study involving chemical synthesis and optimization of melittin variants for stability, followed by protease resistance testing and evaluation in a mouse ulcerative colitis model for efficacy and safety.","limitations":"Animal study only — mouse UC model may not fully predict human response; toxicity profile of modified melittin needs thorough assessment; long-term safety unknown; delivery route and dosing for clinical use not optimized; cost of peptide synthesis and modification may be high."},{"rthcId":"RPEP-12939","title":"PLGA/HA sustained-release system loaded with liraglutide for the treatment of diabetic periodontitis through inhibition of necroptosis.","authors":"Pang, Yunqing; Kong, Lingyuan; Li, Yuanyuan; Li, Jiamin; Ma, Qianlong; Qiu, Jing; Wang, Jing","year":2025,"journal":"Materials today. Bio, 31, 101582","doi":"10.1016/j.mtbio.2025.101582","pmid":"40051526","tags":["glp1-receptor-agonists","drug-delivery-systems","inflammation-immunity","diabetes-glucose-metabolism"],"studyType":"animal-study","evidenceStrength":"low","keyFinding":"PLGA/HA nanoparticles loaded with liraglutide provided sustained local release that reduced diabetic periodontitis severity by inhibiting necroptosis in periodontal tissues, addressing both glycemic control and local tissue destruction.","whyItMatters":"Diabetic periodontitis is a common complication where systemic diabetes worsens local gum disease, and vice versa. Local delivery of a GLP-1 drug addresses both problems simultaneously — controlling blood sugar locally while reducing the inflammatory destruction of gum tissue.","specificNumbers":"PLGA nanoparticles (30,000 Da) had 86.2% encapsulation efficiency and 4.3% drug loading. Cumulative liraglutide release reached about 60% after 8 days. Tested in diabetic rat periodontitis model.","methodology":"Animal study in diabetic rats with periodontitis. Developed and characterized PLGA nanoparticles loaded with liraglutide in a HA scaffold. Assessed particle morphology, size, drug release kinetics, and in vivo efficacy on periodontal inflammation and bone loss.","limitations":"Animal study in rats — dental anatomy and disease progression differ from humans; long-term stability and degradation of the HA/PLGA system in the oral environment needs assessment; comparison with standard periodontal treatments not performed; scale-up for clinical use unaddressed."},{"rthcId":"RPEP-12940","title":"RGD-grafted dextran methacrylate hydrogel incorporating osteogenic peptide and Mn3O4 nanozymes for enhanced bone defect healing.","authors":"Pang, Yuxuan; Wang, Xin; Zhang, Huan; Li, Xin; Lin, Min; Cheng, Liang; Yang, Ying-Wei","year":2025,"journal":"Materials today. Bio, 35, 102436","doi":"10.1016/j.mtbio.2025.102436","pmid":"41158713","tags":["bone-joint-health","drug-delivery-systems","inflammation-immunity","tissue-engineering-regeneration"],"studyType":"animal-study","evidenceStrength":"low","keyFinding":"The triple-component hydrogel (RGD@DEXMA/DOPA-P24/Mn3O4) synergistically reduced ROS-driven inflammation, promoted M1-to-M2 macrophage polarization and angiogenesis, and enhanced osteogenic differentiation of bone marrow stem cells, accelerating bone defect regeneration in vivo.","whyItMatters":"Bone defects often heal poorly because excessive inflammation disrupts the cooperation between immune cells and bone-forming cells. This hydrogel addresses both problems simultaneously—calming inflammation while actively promoting bone growth through sustained peptide release—offering a potential advance in regenerative orthopedic materials.","specificNumbers":"Mn3O4 nanozymes scavenged ROS and induced M1-to-M2 macrophage polarization. DOPA moiety enabled sustained release of P24 peptide. RGD sequence promoted BMSC adhesion and proliferation. Tested in vivo in bone defect models.","methodology":"In vitro cell culture studies with BMSCs and macrophages plus in vivo bone defect models in animals, evaluating ROS scavenging, macrophage polarization, angiogenesis, and bone regeneration.","limitations":"The study used animal models, and results may not directly translate to human bone healing. Long-term safety and degradation profiles of the nanozyme component were not extensively characterized. Specific quantitative outcomes (e.g., bone volume fractions) were not highlighted in the abstract."},{"rthcId":"RPEP-12941","title":"Decoding the impact of exercise and αCGRP signaling on murine post-traumatic osteoarthritis progression.","authors":"Pann, Patrick; Kalke, Paul; Maier, Verena; Schäfer, Nicole; Clausen-Schaumann, Hauke; Schilling, Arndt F; Grässel, Susanne","year":2025,"journal":"Arthritis research & therapy, 27(1), 129","doi":"10.1186/s13075-025-03589-6","pmid":"40544314","tags":["cgrp","bone-joint-health","inflammation-immunity","exercise-performance"],"studyType":"animal-study","evidenceStrength":"low","keyFinding":"αCGRP deficiency did not change overall cartilage degradation scores but prevented cartilage extracellular matrix stiffening, altered subchondral bone remodeling, caused trabecular bone loss with intense exercise, and elevated proinflammatory serum markers—establishing αCGRP as a key mediator of joint and bone responses to mechanical stress during OA.","whyItMatters":"Understanding how neuropeptides like αCGRP regulate the joint response to exercise could lead to targeted therapies for osteoarthritis. If αCGRP signaling can be modulated, it may help protect bone and cartilage integrity during physical activity in people with OA.","specificNumbers":"Used DMM (destabilization of medial meniscus) surgery in C57Bl/6J and alpha-CGRP knockout mice. Moderate and intense treadmill exercise for up to 6 weeks (8 weeks post-surgery). Measured cartilage degradation, bone morphology (nanoCT), and cartilage stiffness (AFM).","methodology":"Controlled animal study using αCGRP knockout vs. wild-type mice with surgically induced OA (DMM model), subjected to moderate or intense treadmill exercise for 6 weeks. Assessed via histology, nanoCT imaging, atomic force microscopy, and multiplex serum immunoassays.","limitations":"Murine model only—results may not directly translate to human OA. Only male mice were studied. Exercise was treadmill-based and may not reflect all types of physical activity. The DMM model represents post-traumatic OA specifically, not age-related OA."},{"rthcId":"RPEP-12942","title":"Natriuretic Peptides as Multisystem Regulators: From Clinical Biomarkers to Therapeutic Targets in Cardio-immunology.","authors":"Panneflek, Jathniel; Barbarawi, Mahmoud; Kakarlapudi, Yasitha; Barbarawi, Zaid; Lauzea, Béatrice; Meraz-Torres, Manolo","year":2025,"journal":"Cardiovascular drugs and therapy","doi":"10.1007/s10557-025-07821-y","pmid":"41369834","tags":["natriuretic-peptides","cardiovascular-health","heart-failure","inflammation-immunity","kidney-renal-health"],"studyType":"narrative-review","evidenceStrength":"moderate","keyFinding":"Natriuretic peptides act as multisystem regulators with natriuretic, vasodilatory, antifibrotic, and immunomodulatory effects via cGMP-PKG signaling, but their therapeutic potential is limited by NP resistance mechanisms including neprilysin degradation, NPR-C clearance, and receptor desensitization in advanced disease.","whyItMatters":"Understanding natriuretic peptides as therapeutic targets rather than just diagnostic markers could unlock new treatment strategies for heart failure, obesity-related cardiovascular disease, and immune-cardiometabolic syndromes. Overcoming NP resistance is key to realizing this potential.","specificNumbers":"Reviews PARADIGM-HF, PARAGON-HF, and EMPEROR-Preserved trial data. Discusses ARNIs, designer peptides, NPR-C modulation, and receptor sensitizers as therapeutic approaches.","methodology":"Narrative review integrating human physiology, preclinical studies, and major clinical trials (PARADIGM-HF, PARAGON-HF, EMPEROR-Preserved), plus analysis of emerging therapeutic agents.","limitations":"This is a narrative review, not a systematic review or meta-analysis. Many of the proposed therapeutic strategies remain preclinical or in early-phase trials. The translational roadmap proposed is largely theoretical and requires validation."},{"rthcId":"RPEP-12943","title":"The renin-angiotensin system in healthy human platelets: expressed but inactive.","authors":"Panosetti, François; Cuenot, François M; Saint Auguste, Damian S; Martins Cavaco, Ana C; Nunes, Allancer D C; Lu, Philip H J; Magrini, Céline; Molot, Max; Sanglard, Gabriel; Günçü, Rodi; Zouaghi, Yassine; Béguelin, Charles; Martins Lima, Augusto; Stergiopulos, Nikolaos","year":2025,"journal":"Platelets, 36(1), 2546982","doi":"10.1080/09537104.2025.2546982","pmid":"40820523","tags":["cardiovascular-health","inflammation-immunity"],"studyType":"in-vitro","evidenceStrength":"low","keyFinding":"Healthy human platelets express RAS receptors (Mas, MrgD, ACE, ACE2, AT1, AT2) but angiotensin peptides (Ang-I, Ang-II, Ang-(1-7), Ang-(1-9), alamandine) had no effect on platelet adhesion or aggregation at any concentration tested. ACE activity was present but captopril-resistant; ACE2 was undetectable.","whyItMatters":"This negative finding is important because it helps rule out direct RAS-platelet interactions as a mechanism for COVID-19 coagulopathy, redirecting research toward other pathways. It also clarifies the functional status of RAS components in platelets.","specificNumbers":"Tested Captopril, Alamandine, Angiotensin-I, Angiotensin-II, Angiotensin-(1-7), and Angiotensin-(1-9) across a wide range of concentrations. Measured adhesion by BCECF fluorescence and aggregation by aggregometry.","methodology":"Ex vivo study on healthy human platelets using western blot and immunofluorescence for receptor expression, spectrophotometry for adhesion, aggregometry for activation/aggregation, and fluorescent peptide substrates for enzyme activity.","limitations":"Study used only healthy donor platelets—results may differ in disease states (COVID-19, hypertension) where RAS is dysregulated. Ex vivo conditions may not fully replicate in vivo platelet behavior. The captopril-resistant ACE activity suggests a non-canonical form that warrants further investigation."},{"rthcId":"RPEP-12944","title":"Ferroptosis and pyroptosis in diabetes mellitus: emerging therapeutic potential of GLP-1 receptor agonists.","authors":"Panou, Theodoros; Gouveri, Evanthia; Rizzo, Manfredi; Popovic, Djordje S; Papanas, Nikolaos","year":2025,"journal":"Frontiers in clinical diabetes and healthcare, 6, 1657710","doi":"10.3389/fcdhc.2025.1657710","pmid":"41244507","tags":["glp1-receptor-agonists","diabetes-glucose-metabolism","kidney-renal-health","liver-health"],"studyType":"narrative-review","evidenceStrength":"moderate","keyFinding":"GLP-1RAs reduced ferroptosis markers (decreased ACSL4, increased protective factors) comparably to ferrostatin-1 and suppressed pyroptosis markers (caspase-1, GSDMD, IL-1β, NLRP3) in experimental models of diabetic kidney disease and metabolic liver disease, with additional anti-inflammatory, anti-fibrotic, and antioxidant effects.","whyItMatters":"Diabetic kidney disease and metabolic liver disease are major complications of diabetes with limited treatment options. If GLP-1 drugs can protect organ tissue by preventing these specific forms of cell death, it adds a powerful mechanistic rationale for their use beyond blood sugar and weight control.","specificNumbers":"GLP-1RAs reduced ACSL4 (ferroptosis marker), increased protective factors, and decreased caspase-1, GSDMD, and IL-1-beta (pyroptosis markers) in experimental models of diabetic kidney disease and MASLD.","methodology":"Narrative review synthesizing experimental (in vitro and animal model) evidence on GLP-1RA effects on ferroptosis and pyroptosis in diabetes and diabetic complications.","limitations":"All evidence is from experimental models (cell cultures and animals). No clinical trial data exists for these specific mechanisms. The review is narrative, not systematic. Translation from experimental findings to human clinical benefit is uncertain."},{"rthcId":"RPEP-12945","title":"Orforglipron in type 2 diabetes mellitus and obesity: an overview.","authors":"Panou, Theodoros; Gouveri, Evanthia; Popovic, Djordje S; Papanas, Nikolaos","year":2025,"journal":"Expert review of clinical pharmacology, 18(11), 883-898","doi":"10.1080/17512433.2025.2594493","pmid":"41275408","tags":["glp1-receptor-agonists","obesity-weight-management","diabetes-glucose-metabolism"],"studyType":"narrative-review","evidenceStrength":"moderate","keyFinding":"Orforglipron achieved HbA1c reductions of up to 2.10%, weight loss up to 13.0 kg (obesity) or 10.1 kg (T2DM), waist circumference reductions up to 8.7 cm, and significant blood pressure decreases. Meta-analyses ranked it the most efficient GLP-1RA for weight loss.","whyItMatters":"Current GLP-1 drugs like semaglutide require injections, which limits patient acceptance and access. An effective oral non-peptide alternative could dramatically expand who benefits from GLP-1 therapy for diabetes and obesity.","specificNumbers":"HbA1c reduction up to 2.10%. Weight loss up to 10.1 kg in T2DM and up to 13.0 kg in obesity. Waist circumference reduction up to 8.7 cm. Significant systolic blood pressure decreases also reported.","methodology":"Systematic overview based on electronic searches of Scopus, PubMed/MEDLINE, and Google Scholar, synthesizing clinical trial data and meta-analyses on orforglipron.","limitations":"Review is based on available clinical trial data; long-term safety and cardiovascular outcome data are still pending. Higher doses and rapid escalation caused significant GI side effects. Comparison to injectable GLP-1RAs in head-to-head trials is limited."},{"rthcId":"RPEP-12946","title":"GLP-1 receptor agonists and sarcopenia: Weight loss at a cost? A brief narrative review.","authors":"Pantazopoulos, Dimitrios; Gouveri, Evanthia; Papazoglou, Dimitrios; Papanas, Nikolaos","year":2025,"journal":"Diabetes research and clinical practice, 229, 112924","doi":"10.1016/j.diabres.2025.112924","pmid":"41022269","tags":["glp1-receptor-agonists","obesity-weight-management","muscle-skeletal-health","aging-longevity"],"studyType":"narrative-review","evidenceStrength":"moderate","keyFinding":"Clinical studies show GLP-1RAs and dual GLP-1/GIP agonists can cause significant lean mass loss and sarcopenia risk, but preclinical evidence paradoxically shows these agents may attenuate skeletal muscle atrophy, improve muscle function, and enhance mitochondrial health at the cellular level.","whyItMatters":"With millions now taking GLP-1 drugs for weight loss, understanding whether muscle loss is an inevitable side effect or a manageable concern is critical. Sarcopenia—loss of muscle mass and function—can lead to frailty, falls, and metabolic decline, especially in older adults.","specificNumbers":"GLP-1 RAs and dual GLP-1/GIP RAs linked to significant lean mass reductions in clinical studies. Preclinical data show improved mitochondrial health and attenuated muscle atrophy. GDF8 and activin A blockade proposed as countermeasures.","methodology":"Brief narrative review synthesizing clinical and preclinical evidence on the relationship between GLP-1-based therapies and muscle health.","limitations":"Narrative review with limited systematic methodology. Preclinical muscle-protective findings may not translate to clinical settings. Clinical data on lean mass preservation strategies during GLP-1 therapy are limited. The review does not distinguish between lean mass types (muscle vs. organ tissue)."},{"rthcId":"RPEP-12947","title":"Pharmacokinetic considerations for gonadotropin-releasing hormone agonists and antagonists to treat endometriosis.","authors":"Paoletti, Anna Maria; Neri, Manuela; Pilloni, Monica; Marotto, Maria Francesca; Giancane, Elena; Vallerino, Valerio; Piras, Bruno; Melis, Giulia; Melis, Virginia; Masciale, Michele Danilo Maria; Murgia, Enrica; Melis, Gian Benedetto","year":2025,"journal":"Expert opinion on drug metabolism & toxicology, 21(6), 649-663","doi":"10.1080/17425255.2025.2499550","pmid":"40315284","tags":["hormones-endocrine","reproductive-health"],"studyType":"narrative-review","evidenceStrength":"moderate","keyFinding":"Non-peptide GnRH antagonists combine the benefits of rapid onset (no flare-up effect), oral administration, and dose-dependent estrogen suppression, offering advantages over both GnRH agonists (delayed onset, injection required) and peptide antagonists (injection required) for endometriosis treatment.","whyItMatters":"Endometriosis affects roughly 10% of reproductive-age women and causes significant pain and disability. Moving from injectable peptide-based therapies to oral non-peptide alternatives makes long-term treatment more accessible and allows dose adjustment to balance symptom relief against side effects.","specificNumbers":"GnRH agonists induce hypoestrogenism after 10-12 days (initial flare-up). Peptide antagonists block receptors immediately. Target estradiol range: 40-50 pg/mL to suppress endometriotic growth while minimizing bone loss.","methodology":"Narrative review based on electronic literature search of pharmacological features of GnRH agonists and antagonists for endometriosis treatment.","limitations":"Narrative review without systematic methodology or meta-analysis. Long-term comparative efficacy and safety data between drug classes are still evolving. Add-back therapy protocols vary and were not comprehensively compared."},{"rthcId":"RPEP-12948","title":"Animal models of lean metabolic dysfunction-associated steatotic liver disease (MASLD): bridging pathogenesis and novel drug discovery.","authors":"Papadakos, Stavros P; Georgiadou, Chara; Kassi, Eva; Velliou, Rallia-Iliana; Chatzigeorgiou, Antonios","year":2025,"journal":"Expert opinion on drug discovery, 20(12), 1683-1700","doi":"10.1080/17460441.2025.2579124","pmid":"41131939","tags":["glp1-receptor-agonists","liver-health","diabetes-glucose-metabolism"],"studyType":"narrative-review","evidenceStrength":"moderate","keyFinding":"Lean MASLD is mechanistically distinct from obesity-related MASLD, driven by bile acid dysregulation, leptin signaling abnormalities, and oxidative stress. Animal models testing GLP-1 analogues (exendin-4, liraglutide), kinsenoside, silibinin, and bile acid modulators show therapeutic promise for this patient population.","whyItMatters":"Lean MASLD is often underdiagnosed because patients lack the obesity typically associated with fatty liver disease. Understanding its unique mechanisms through appropriate animal models is essential for developing targeted therapies, including peptide-based treatments, for this overlooked patient population.","specificNumbers":"Literature search: PubMed and Scopus, January 2000 to June 2025. Models reviewed include MCD diet, choline-deficient diet, cholesterol/bile acid diets, Pemt-/- and cGas-/- genetic models. Candidate therapies include exendin-4 (GLP-1 analog).","methodology":"Systematic literature review of PubMed and Scopus (January 2000-June 2025) covering dietary, genetic, and bile acid-focused animal models of lean MASLD.","limitations":"Animal models cannot fully replicate human lean MASLD. Most therapeutic candidates are at preclinical stages. The review acknowledges that no single animal model captures all features of human lean MASLD."},{"rthcId":"RPEP-12949","title":"Hypoalbuminemia, but not derived neutrophil to lymphocyte ratio (dNLR), predicts overall survival in neuroendocrine tumours undergoing peptide receptor radionuclide therapy: A retrospective, cohort study of 557 patients.","authors":"Papantoniou, Dimitrios; Fröss-Baron, Katarzyna; Garske-Román, Ulrike; Sundin, Anders; Thiis-Evensen, Espen; Grönberg, Malin; Welin, Staffan; Tiensuu Janson, Eva","year":2025,"journal":"Journal of neuroendocrinology, 37(3), e13379","doi":"10.1111/jne.13379","pmid":"38477040","tags":["peptide-receptor-radionuclide-therapy","neuroendocrine-tumors"],"studyType":"retrospective-cohort","evidenceStrength":"moderate","keyFinding":"Hypoalbuminemia (HR 0.91 per unit) and elevated CRP (HR 1.02 per unit) independently predicted shorter overall survival in PRRT-treated NET patients. GPS score of 2 vs. 0 had HR 3.60. Albumin was the single most valuable addition to established prognostic models, while dNLR added no value.","whyItMatters":"PRRT is a major peptide-based cancer therapy for neuroendocrine tumors. Identifying which patients benefit most through simple blood tests like albumin and CRP could help clinicians personalize treatment decisions and avoid exposing unlikely responders to radiation.","specificNumbers":"557 patients, treated 2005-2015. Albumin HR: 0.91 per unit (95% CI: 0.87-0.95). GPS 2 vs 0 HR: 3.60 (95% CI: 2.24-5.79). CRP/albumin ratio HR: 1.84 (95% CI: 1.43-2.37). dNLR was not significant.","methodology":"Retrospective cohort study of 557 NET patients treated with PRRT at a tertiary referral center (2005-2015), using Cox proportional hazard models and Akaike information criterion for model comparison.","limitations":"Retrospective single-center design limits generalizability. Blood markers were measured at variable time points relative to PRRT. ESR analysis was exploratory in a subset only. The study did not assess whether modifying inflammation markers could improve outcomes."},{"rthcId":"RPEP-12950","title":"A Short-Term Cost-Effectiveness Analysis of Tirzepatide Versus Semaglutide for the Treatment of Obesity in Greece.","authors":"Papantoniou, Panagiotis; Maniadakis, Nikolaos","year":2025,"journal":"Healthcare (Basel, Switzerland), 13(16)","doi":"10.3390/healthcare13162011","pmid":"40868627","tags":["tirzepatide","semaglutide","obesity-weight-management"],"studyType":"cost-effectiveness-analysis","evidenceStrength":"moderate","keyFinding":"Tirzepatide cost €5,646 vs semaglutide €3,202 over 72 weeks. Semaglutide showed numerically lower cost per responder at ≥10% weight loss; tirzepatide was favored at ≥25-30% targets. Probabilistic analysis showed no statistically significant difference at any threshold.","whyItMatters":"With two competing GLP-1-based obesity drugs now available, healthcare systems need data to guide coverage decisions. This analysis suggests the choice between tirzepatide and semaglutide may depend more on individual weight loss goals than overall cost-effectiveness.","specificNumbers":"Weight loss targets: >= 10%, >= 15%, >= 20%, >= 25%, >= 30%. Based on SURMOUNT-5 phase 3b trial over 72 weeks. Greek payer (EOPYY) perspective. Direct medical costs only.","methodology":"Short-term cost-effectiveness analysis from the Greek third-party payer perspective using SURMOUNT-5 trial data (72-week, phase 3b, head-to-head) comparing direct medical costs and weight loss target achievement rates.","limitations":"Short 72-week horizon does not capture long-term outcomes or complications prevented. Greek-specific pricing may not apply elsewhere. Based on a single head-to-head trial. Only direct medical costs included; indirect costs (productivity, comorbidity reduction) were excluded."},{"rthcId":"RPEP-12951","title":"Cost-effectiveness of semaglutide 2.4 mg versus liraglutide 3 mg for the treatment of obesity in Greece.","authors":"Papantoniou, Panagiotis; Maniadakis, Nikolaos","year":2025,"journal":"Frontiers in public health, 13, 1690211","doi":"10.3389/fpubh.2025.1690211","pmid":"41229480","tags":["semaglutide","glp1-receptor-agonists","obesity-weight-management"],"studyType":"cost-effectiveness-analysis","evidenceStrength":"moderate","keyFinding":"Semaglutide 2.4 mg yielded an ICER of €12,724 per QALY gained versus liraglutide 3 mg. In probabilistic sensitivity analysis, semaglutide dominated liraglutide (higher QALYs at lower cost) in 80.8% of simulations and reached 100% cost-effectiveness probability at a €9,000/QALY threshold.","whyItMatters":"Cost-effectiveness data directly influences which peptide drugs get government reimbursement and therefore patient access. This analysis supports expanding access to semaglutide for obesity treatment in Greece, where currently only liraglutide is reimbursed.","specificNumbers":"Modeled BMI >= 35 kg/m2 with >= 1 comorbidity. 40-year time horizon. 3.5% annual discount rate. Costs in 2025 euros. Outcomes in LYs and QALYs. Based on STEP-8 trial data.","methodology":"State-transition economic model with 40-year time horizon, using STEP-8 trial efficacy data, Greek cost inputs (2025 euros), 3.5% annual discount rate, with deterministic, scenario, and probabilistic sensitivity analyses from the Greek third-party payer perspective.","limitations":"Based on a single clinical trial (STEP-8) for efficacy inputs. Long-term outcomes projected from models, not observed data. Specific to Greek cost structure and healthcare system. Limited to patients with BMI ≥35 and weight-related comorbidities."},{"rthcId":"RPEP-12952","title":"Obesity and insulinopenic type 2 diabetes differentially impact, bone phenotype, bone marrow adipose tissue, and serum levels of the cathelicidin-related antimicrobial peptide in mice.","authors":"Paquet, Amélie; Bahlouli, Nadia; Coutel, Xavier; Leterme, Damien; Delattre, Jérôme; Gauthier, Véronique; Miellot, Flore; Delplace, Séverine; Rouge-Labriet, Hélène; Bertheaume, Nicolas; Chauveau, Christophe; Benachour, Hamanou","year":2025,"journal":"Bone, 193, 117387","doi":"10.1016/j.bone.2024.117387","pmid":"39742907","tags":["antimicrobial-peptides","bone-joint-health","diabetes-glucose-metabolism","obesity-weight-management"],"studyType":"animal-study","evidenceStrength":"low","keyFinding":"Hyperinsulinemic obesity decreased trabecular and cortical bone thickness with BMAT expansion but preserved CRAMP levels. Insulinopenic T2D decreased trabecular number, impaired bone stiffness, and reduced circulating CRAMP peptide levels, suggesting a link between insulin deficiency, bone quality, and innate immune peptide regulation.","whyItMatters":"Both obesity and diabetes increase fracture risk, but through different mechanisms. Understanding that the antimicrobial peptide CRAMP is specifically reduced in insulinopenic diabetes—not obesity—could reveal new biomarkers for diabetes-related bone fragility and potential therapeutic targets at the intersection of innate immunity and bone health.","specificNumbers":"C57BL/6J male mice on high-fat diet (16 weeks) for obesity model. Streptozotocin + HFD for insulinopenic T2D model. Compared to low-fat diet controls. Assessed bone phenotype and bone marrow adipose tissue.","methodology":"Controlled animal study using C57BL/6J male mice with high-fat diet (HFD) for obesity and HFD + streptozotocin (STZ) for insulinopenic T2D, assessed over 8-16 weeks via micro-CT bone analysis, biomechanical testing, BMAT quantification, and serum CRAMP measurement.","limitations":"Mouse model only—STZ-induced diabetes does not perfectly replicate human T2D pathophysiology. Only male mice studied. Correlation between CRAMP reduction and bone changes does not establish causation. Human cathelicidin (LL-37) may behave differently than mouse CRAMP."},{"rthcId":"RPEP-12953","title":"Sensory neuropeptide CGRP and its co-receptor RAMP1 drive tumour cell growth in gastrointestinal cancers.","authors":"Parathan, Pavitha; Tran, Kelly; Neil, Liam; Tan, Tao; Carli, Annalisa L E; Liao, Yang; Mouradov, Dmitri; Da Gama Duarte, Jessica; Huber, Anne; Pal, Bhupinder; Gibbs, Peter; Sieber, Oliver M; Chiu, Isaac M; Kearney, Conor J; Shi, Wei; Mariadason, John M; Williams, David S; Buchert, Michael; Mielke, Lisa A","year":2025,"journal":"BMJ oncology, 4(1), e000842","doi":"10.1136/bmjonc-2025-000842","pmid":"41158750","tags":["cgrp","cancer-oncology","gastrointestinal-health"],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"RAMP1 expression was associated with reduced survival in CRC and GC. Over 50% of CRC and 60% of GC cells expressed RAMP1. Tumor cells themselves produced CGRP (not just nerves). CGRP stimulation enhanced tumor growth in a RAMP1-dependent manner, activating proliferation, metabolism, and migration pathways.","whyItMatters":"This study reveals that gastrointestinal cancers can exploit and even produce neuropeptides to fuel their own growth, opening a new therapeutic avenue. CGRP-blocking drugs already exist for migraine—they could potentially be repurposed for cancer treatment.","specificNumbers":"180 patient samples analyzed using multiplex immunohistochemistry. Included primary colorectal cancer, CRC liver metastases, and gastric cancers. RAMP1 expression correlated with pathological features and molecular subtypes. TCGA data used for survival analysis.","methodology":"Analysis of 180 patient samples using multiplex immunohistochemistry, TCGA survival data analysis, in vitro stimulation assays on tumor cell lines and patient-derived organoids, and RNA sequencing for mechanistic pathway analysis.","limitations":"Primarily correlative in patient samples; mechanistic work limited to in vitro and organoid models. No in vivo tumor treatment studies. CGRP-blocking therapies for cancer remain untested. Association between RAMP1 expression and survival does not prove causation."},{"rthcId":"RPEP-12954","title":"Real-world evaluation of the efficacy and safety of switching from weekly dulaglutide to weekly semaglutide: The SEMA-SWITCH study.","authors":"Pardo Lozano, Felipe; Rubio Marcos, Arantxa; Casañ Fernández, Rosa; Bartual Rodrigo, Amparo; Martínez-Hervás, Sergio; Ampudia-Blasco, Francisco Javier","year":2025,"journal":"Endocrinologia, diabetes y nutricion, 72(6), 501574","doi":"10.1016/j.endien.2025.501574","pmid":"40450456","tags":["semaglutide","glp1-receptor-agonists","diabetes-glucose-metabolism"],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"After switching from dulaglutide to semaglutide, patients achieved additional HbA1c reductions of -0.43% (6 mo), -0.54% (12 mo), -0.38% (18 mo), and additional weight loss of -2.7 kg (6 mo), -3.7 kg (12 mo), -5.4 kg (18 mo), -4.2 kg (24 mo), with no significant increase in adverse effects.","whyItMatters":"Many patients on GLP-1 drugs reach a plateau or have suboptimal results. This study provides real-world evidence that switching between GLP-1 agonists—specifically from dulaglutide to semaglutide—can unlock additional metabolic benefits without added risk.","specificNumbers":"123 patients. Prior dulaglutide duration: 16.9 months. Dulaglutide reduced HbA1c by 0.38% and weight by 1.3 kg. After switching to semaglutide: additional HbA1c reductions of 0.43% (6 mo), 0.54% (12 mo), 0.38% (18 mo), 0.12% (24 mo). Additional weight loss up to 5.5 kg.","methodology":"Real-world observational cohort study (SEMA-SWITCH) of 123 patients with T2DM who switched from subcutaneous dulaglutide to subcutaneous semaglutide, followed for up to 24 months with HbA1c and weight measurements.","limitations":"Observational design without a control group (no comparison to continuing dulaglutide). Selection bias: patients who switched may have been more motivated. Relatively small sample size. HbA1c benefit diminished by 24 months. No randomization."},{"rthcId":"RPEP-12955","title":"Toxicity manifestations encountered in peptide receptor radionuclide therapy setting.","authors":"Parghane, Rahul V; Basu, Sandip","year":2025,"journal":"Journal of neuroendocrinology, 37(3), e13464","doi":"10.1111/jne.13464","pmid":"39531370","tags":["peptide-receptor-radionuclide-therapy","neuroendocrine-tumors"],"studyType":"narrative-review","evidenceStrength":"moderate","keyFinding":"PRRT toxicities are stratified into acute (nausea, hormone-related crises), subacute (bone marrow suppression, kidney effects), and long-term (renal impairment, myelodysplastic syndrome). Most side effects are transient, but awareness of high-risk factors is essential for prevention and early management.","whyItMatters":"As PRRT becomes more widely used for neuroendocrine tumors, clinicians need practical guidance on managing its toxicity profile. Understanding risk factors allows for patient selection optimization and proactive toxicity prevention, maximizing the benefit-to-risk ratio of this peptide-based therapy.","specificNumbers":"Toxicities stratified by onset: acute (during/shortly after), subacute (weeks to months), and long-term (months to years). Reviews kidney toxicity, hematological toxicity, and rare secondary malignancies.","methodology":"Comprehensive narrative review of toxicity data from PRRT clinical experience, including risk factor identification, management strategies, and recent advances in toxicity prediction and prevention.","limitations":"Narrative review without systematic methodology or meta-analysis of toxicity rates. Toxicity profiles may vary with different radionuclides and peptide ligands. Risk factor evidence comes largely from retrospective analyses."},{"rthcId":"RPEP-12956","title":"Prior GLP-1 agonist use is not associated with adverse inpatient critical care outcomes: A propensity-matched analysis.","authors":"Park, Albert K; Hom, Jason; Lorenzo, Javier; Rao, Vidya; Hui, Gavin; Vickers, Matthew; Ahuja, Neera","year":2025,"journal":"Journal of hospital medicine","doi":"10.1002/jhm.70228","pmid":"41286572","tags":["glp1-receptor-agonists","muscle-skeletal-health"],"studyType":"retrospective-cohort","evidenceStrength":"moderate","keyFinding":"Prior GLP-1 agonist use showed no association with adverse ICU outcomes: in-hospital mortality 5.1% vs 4.9% (OR 1.05, 95% CI 0.58-1.91), hospital LOS 13.7 vs 13.4 days, ICU LOS 5.9 vs 5.4 days. All differences were non-significant.","whyItMatters":"As millions take GLP-1 drugs and concerns grow about muscle loss side effects, this is the first study examining whether GLP-1 users fare worse during critical illness. The reassuring null finding suggests clinicians need not be concerned about GLP-1-related risks in ICU settings.","specificNumbers":"15,191 eligible ICU patients. 468 (3.1%) had GLP-1 prescriptions within 12 months before admission. 452 propensity-matched pairs analyzed. Similar in-hospital mortality, hospital LOS, and ICU LOS between groups.","methodology":"Retrospective propensity-matched cohort study using Stanford Health Care data (Jan 2015-Jul 2024). 15,191 eligible ICU patients, 468 with prior GLP-1 use, 452 matched pairs created using high-dimensional propensity score matching with lasso regression.","limitations":"Retrospective observational design cannot establish causation. Single-center (Stanford) may limit generalizability. Could not assess GLP-1 dose, duration, or adherence. 3.1% exposure rate may limit power for rare outcomes. No data on functional recovery or ICU-acquired weakness specifically."},{"rthcId":"RPEP-12957","title":"Semaglutide promotes bone marrow-derived progenitor cell flux toward an anti-inflammatory and pro-regenerative profile in high-risk patients: the SEMA-VR CardioLink-15 trial.","authors":"Park, Brady; Dennis, Fallon; He, Arianna Z; Krishnaraj, Aishwarya; Bakbak, Ehab; Dennis, Cole J; Pan, Yi; Misner, Elizabeth; Thayanithy, Veena; Lambotharan, Bhavaani; Lambotharan, Vaasudevan; Lambotharan, Aruna; Mazer, C David; Quan, Adrian; Teoh, Hwee; Hess, David A; Verma, Subodh","year":2025,"journal":"European heart journal","doi":"10.1093/eurheartj/ehaf690","pmid":"40886061","tags":["semaglutide","glp1-receptor-agonists","cardiovascular-health","stem-cells-growth-factors"],"studyType":"randomized-controlled-trial","evidenceStrength":"moderate","keyFinding":"Semaglutide increased VR cells +34.8% (vs +0.8% usual care, p=0.036), endothelial precursors +66.2% (vs -2.3%, p=0.037), and reduced granulocyte precursors -50.8% (vs +0.3%, p=0.002). Pro-inflammatory TNF and interleukin serum proteins were also downregulated.","whyItMatters":"This reveals a previously unknown mechanism by which GLP-1 drugs protect the cardiovascular system—by enhancing the body's natural blood vessel repair capacity through stem and progenitor cell mobilization while suppressing inflammatory cells that damage blood vessels.","specificNumbers":"46 participants (22 semaglutide, 24 usual care). 6-month treatment. VR cells (ALDHhi SSClow) increased 34.8% with semaglutide vs 0.8% with usual care (P = 0.036). Myeloid progenitors up 40.1% vs 2.8% (P = 0.017). Endothelial precursors up 66.2% vs down 2.3%.","methodology":"Randomized translational trial (SEMA-VR CardioLink-15) of 46 participants with T2D/obesity plus ASCVD or ASCVD risk factors. 22 received semaglutide, 24 usual care for 6 months. Multi-parametric flow cytometry for VR cell enumeration.","limitations":"Small sample size (n=46). Open-label design (not blinded). Translational trial measuring surrogate cell markers, not clinical cardiovascular events. Six-month duration may not capture long-term effects. Mechanistic connection between VR cell increases and clinical outcomes is inferential."},{"rthcId":"RPEP-12958","title":"Cathelicidin antimicrobial peptides mediate immune protection in marsupial neonates.","authors":"Park, Jongbeom; Ke, Wenfan; Kaage, Aellah; Feigin, Charles Y; Griffing, Aaron H; Pritykin, Yuri; Donia, Mohamed S; Mallarino, Ricardo","year":2025,"journal":"Science advances, 11(16), eads6359","doi":"10.1126/sciadv.ads6359","pmid":"40238884","tags":["antimicrobial-peptides","inflammation-immunity"],"studyType":"animal-study","evidenceStrength":"low","keyFinding":"Sugar glider cathelicidins reside in two genomic clusters, are highly expressed in neonatal neutrophils, have potent antibacterial activity, modulate immune responses, and provide sufficient protection against sepsis in a mouse model. Marsupials and monotremes uniquely retain both genomic clusters among tetrapods.","whyItMatters":"Cathelicidins are a crucial family of antimicrobial peptides shared across mammals, including humans (LL-37). Discovering that marsupials have an expanded repertoire with proven sepsis protection could inspire novel peptide-based anti-infective therapies and reveal new biology about how these peptides evolved to meet different immune challenges.","specificNumbers":"Sugar glider cathelicidins reside in two genomic clusters with shared enhancers and long-range interactions. Provided protection in a mouse sepsis model. Marsupials and monotremes uniquely retain both clusters among tetrapods.","methodology":"Genomic analysis of cathelicidin gene clusters, gene expression profiling in developing neutrophils, functional antibacterial and immunomodulatory assays, and in vivo sepsis protection testing in a mouse model using sugar glider (Petaurus breviceps).","limitations":"Primary focus on marsupial biology limits direct human clinical translation. Mouse sepsis model provides proof of concept but is not equivalent to human infection. Specific peptide sequences with greatest therapeutic potential were not individually characterized. Evolutionary focus may limit practical application."},{"rthcId":"RPEP-12959","title":"Peptide PN5 from Pinus densiflora Confers in Vivo Protection Against Multidrug-Resistant Salmonella Typhimurium Through Membrane Disruption.","authors":"Park, Jonggwan; Kang, Da Dam; Kim, Hyeongsun; Oh, Jun Hee; Park, Yoonkyung","year":2025,"journal":"ACS omega, 10(50), 61322-61338","doi":"10.1021/acsomega.5c06012","pmid":"41476542","tags":["antimicrobial-peptides","inflammation-immunity","drug-delivery-systems"],"studyType":"animal-study","evidenceStrength":"low","keyFinding":"PN5 demonstrated dual-function activity: direct bactericidal membrane disruption against MDR S. Typhimurium plus immune modulation via NF-κB and MAPK pathways. It eliminated intracellular bacteria in macrophages, inhibited biofilm formation, and significantly improved survival in a murine infection model.","whyItMatters":"Multidrug-resistant Salmonella is a growing public health threat with limited treatment options. A natural peptide that both kills resistant bacteria directly and helps the immune system clear infection represents a fundamentally different approach than conventional antibiotics.","specificNumbers":"PN5 was stable across diverse pH and temperature conditions. Inhibited biofilm formation. Eliminated intracellular S. Typhimurium in RAW 264.7 macrophages. Modulated NF-kB and MAPK signaling. Improved survival in murine infection model.","methodology":"In vitro antibacterial assays (MIC, membrane disruption, biofilm inhibition, cytotoxicity), intracellular killing assays in RAW 264.7 macrophages, signaling pathway analysis (NF-κB, MAPK), and in vivo murine S. Typhimurium infection model.","limitations":"Derived from a plant source; scalability and cost of production need evaluation. Only tested against S. Typhimurium; activity against other MDR pathogens is unknown. Mouse model results require validation in larger animals and eventually humans. Pharmacokinetic properties not characterized."},{"rthcId":"RPEP-12960","title":"Impact of Liraglutide 3.0 mg on Metabolic Dysfunction-Associated Steatotic Liver Disease in Individuals with Obesity: A Real-World Study.","authors":"Park, Jungha; Kim, Jin-Wook; Lim, Soo","year":2025,"journal":"Annals of nutrition & metabolism, 81(6), 328-337","doi":"10.1159/000547347","pmid":"40675139","tags":["glp1-receptor-agonists","liver-health","obesity-weight-management"],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"Liraglutide 3.0 mg reduced AST from 33.2 to 27.4 IU/L (p<0.001), ALT from 41.6 to 30.6 IU/L (p<0.001), HSI from 44.7 to 42.2 (p<0.001), and NAFLD liver fat score from 2.12 to 0.43 (p<0.001) over 6 months. Insulin sensitivity improved from 4.38 to 4.72 (p<0.001).","whyItMatters":"MASLD affects a large proportion of people with obesity and can progress to cirrhosis and liver cancer. Demonstrating that a GLP-1 peptide drug improves liver health markers in real clinical practice—not just controlled trials—supports its use as a dual-purpose treatment for obesity and liver disease.","specificNumbers":"503 enrolled, 101 completed 6 months. AST dropped from 33.2 to 27.4 IU/L (P < 0.001). ALT dropped from 41.6 to 30.6 IU/L (P < 0.001). HSI dropped from 44.7 to 42.2 (P < 0.001). NAFLD liver fat score dropped from 2.12 to 0.43 (P < 0.001).","methodology":"Prospective real-world multicenter study across 10 tertiary hospitals in South Korea. 503 adults with BMI ≥27 and obesity-related comorbidities, followed at 2, 4, and 6 months with anthropometric and biochemical assessments.","limitations":"No control group (single-arm observational study). Significant attrition: 503 enrolled but only 101 completed 6 months. Surrogate markers used rather than direct liver imaging or biopsy. Results may partly reflect weight loss effects rather than direct hepatic action."},{"rthcId":"RPEP-12961","title":"Sphingosine-1-Phosphate-Cathelicidin Axis Plays a Pivotal Role in the Development of Cutaneous Squamous Cell Carcinoma.","authors":"Park, Kyungho; Shin, Kyong-Oh; Kim, Young-Il; Nielsen-Scott, Anna L; Mainzer, Carine; Celli, Anna; Bae, Yoojin; Chae, Seungwoo; An, Hahyun; Choi, Yerim; Park, Jae-Ho; Park, Soo-Hyun; Hwang, Jin-Taek; Kang, Seung Goo; Wakefield, Joan S; Arron, Sarah T; Holleran, Walter M; Mauro, Theodora M; Elias, Peter M; Uchida, Yoshikazu","year":2025,"journal":"The Journal of investigative dermatology, 145(4), 854-863.e6","doi":"10.1016/j.jid.2024.08.008","pmid":"39218144","tags":["antimicrobial-peptides","cancer-oncology","skin-dermatology"],"studyType":"in-vitro","evidenceStrength":"low","keyFinding":"CAMP is overexpressed in cSCC and promotes tumor growth via FPRL1 receptor. S1P signaling drives CAMP production; inhibiting S1P reduces CAMP-stimulated cSCC growth. CAMP increases FOXP3+ regulatory T cells (suppressing anti-tumor immunity) and induces ER stress, creating a vicious S1P-CAMP feedback loop that favors cSCC development.","whyItMatters":"Understanding that a normally protective antimicrobial peptide can be hijacked by cancer cells reveals a new therapeutic target. Blocking the S1P-CAMP-FPRL1 axis could provide a novel approach to treating skin cancer while preserving the peptide's antimicrobial benefits in healthy tissue.","specificNumbers":"CAMP expression increased in cSCC cells and patient skin. S1P levels elevated in cSCC cells. Blocking S1P production or FPRL1 receptor attenuated cSCC growth. FOXP3+ regulatory T cells increased in cSCC skin.","methodology":"Combination of patient tissue analysis, in vitro cSCC cell line experiments, receptor blockade studies (FPRL1), S1P pathway inhibition, invasion assays using fibroblast/ECM substrates, and regulatory T cell quantification.","limitations":"Primarily in vitro and ex vivo evidence. No in vivo tumor treatment studies. The relative contribution of CAMP to cSCC development versus other UV-driven pathways is not quantified. Clinical implications of CAMP as a therapeutic target need validation."},{"rthcId":"RPEP-12962","title":"Glucagon-like-peptide-1 agonist therapy in adults with cystic fibrosis.","authors":"Park, Sanghoon; Jain, Raksha; Mirfakhraee, Sasan","year":2025,"journal":"Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society, 24(1), 40-46","doi":"10.1016/j.jcf.2024.08.005","pmid":"39214747","tags":["semaglutide","tirzepatide","glp1-receptor-agonists","respiratory-health"],"studyType":"case-series","evidenceStrength":"very-low","keyFinding":"All 11 CF patients lost weight (median -7.2 kg). 8/11 improved FEV1 (up to +18%), 9/11 improved FVC (up to +26%). All 7 with CFRD reduced insulin (mean -31.5% total daily dose). Glucose time in range improved (mean +11%).","whyItMatters":"As CF life expectancy increases, more patients face obesity and CF-related diabetes. This first substantial report shows GLP-1 drugs may address both while unexpectedly improving lung function—a critical finding for a disease where lung decline is the primary driver of mortality.","specificNumbers":"11 patients (3 male, 7 female, ages 24-47, BMI 25.7-43.7). 9 on semaglutide, 2 on tirzepatide. Duration 1-50 months. Median weight loss 7.2 kg. BMI change -0.9 to -8.1. FEV1 improved in 8 of 11 (change -5 to +18). FVC improved in 9 of 11 (change +1 to +26). Mean insulin reduction 31.5%. 4 discontinued.","methodology":"Retrospective case series of 11 adults with CF (3 male, 7 female, age 24-47, BMI 25.7-43.7) treated with GLP-1 agonists (semaglutide or tirzepatide) for 1-50 months at a single CF center.","limitations":"Very small case series (n=11) without controls. Retrospective design. Single center. Variable treatment duration (1-50 months). Lung function improvements could be confounded by other treatments. 4/11 (36%) discontinued, raising tolerability concerns."},{"rthcId":"RPEP-12963","title":"Preclinical Study of Pain Neuropeptide Expression in Murine Sensory Neurons Induced by Irradiated Osteoclasts in the Context of Stereotactic Body Radiation Therapy.","authors":"Park, Sun H; Peters, Megan; Aguayo, Caleb; Farris, Michael K; Hughes, Ryan T; Moore, Joseph; Munley, Michael T; Reno, Kaitlyn E; Foster, Jeffrey A; Gardin, Jean; Schaaf, George W; Cline, J Mark; Peters, Christopher M; Willey, Jeffrey S","year":2025,"journal":"Cells, 14(17)","doi":"10.3390/cells14171324","pmid":"40940736","tags":["cgrp","neuropeptides-neuroscience","bone-joint-health","pain-management"],"studyType":"in-vitro","evidenceStrength":"very-low","keyFinding":"Radiation-activated osteoclasts released factors that increased pain neuropeptide expression (CGRP, substance P) in sensory neurons. Blocking osteoclast differentiation with osteoprotegerin reduced this effect.","whyItMatters":"Chest wall pain after radiation therapy is common and poorly understood. This study suggests irradiated bone cells signal to nerves, increasing pain peptide production. Blocking this crosstalk could reduce radiation-related pain.","specificNumbers":"10 Gy gamma-irradiation increased TRAP-positive osteoclast size 1.36-fold. Activity markers Ctsk (1.35-fold) and Mmp9 (1.76-fold) increased. Conditioned media from irradiated osteoclasts increased pain neuropeptide expression in sensory neurons.","methodology":"RAW264.7 cells differentiated with RANKL, irradiated at 10 Gy. Conditioned media applied to mouse dorsal root ganglia sensory neuron cultures. RT-qPCR and histochemical staining for osteoclast and pain neuropeptide markers. OPG and risedronate used to block osteoclasts.","limitations":"In vitro cell culture study. Does not replicate the complexity of in vivo radiation pain. Mouse cell lines may not reflect human biology. Single radiation dose tested."},{"rthcId":"RPEP-12964","title":"Efficacy and safety of low-molecular-weight collagen peptides in knee osteoarthritis: a randomized, double-blind, placebo-controlled trial.","authors":"Park, Sun-Young; Lee, Sang-Hyun; Kim, Hyun Tae; Park, Hye-Jin; Kim, Do-Un; Kim, Seung Un; Heo, In","year":2025,"journal":"Frontiers in nutrition, 12, 1644899","doi":"10.3389/fnut.2025.1644899","pmid":"40977985","tags":["collagen-peptides","bone-joint-health","pain-management"],"studyType":"randomized-controlled-trial","evidenceStrength":"moderate","keyFinding":"Low-molecular-weight collagen peptides (3,000 mg/day) reduced knee osteoarthritis pain and improved physical function over 180 days compared to placebo in a double-blind trial of 80 patients.","whyItMatters":"Knee OA has few safe long-term treatments. This trial provides controlled evidence that collagen peptide supplements can reduce pain and improve function, offering a low-risk nutritional approach.","specificNumbers":"80 adults aged 40-75 with KL grade I-II OA. 3,000 mg/day LMCP vs placebo for 180 days. WOMAC pain change: -1.90 vs +0.61 (P = 0.006). WOMAC physical function and total scores also improved in the LMCP group.","methodology":"Double-blind, randomized, placebo-controlled trial. 80 participants with KL grade I-II knee OA. Primary endpoint: WOMAC pain. Secondary: VAS, WOMAC function, joint space width, inflammatory markers. 180-day follow-up.","limitations":"Small sample size (80 participants). Only mild OA (KL grade I-II). 180-day duration may not capture long-term effects. Single study needs replication."},{"rthcId":"RPEP-12965","title":"Worsening vasomotor symptoms in the setting of estradiol and semaglutide: a case report.","authors":"Parker, Anna E","year":2025,"journal":"Menopause (New York, N.Y.)","doi":"10.1097/GME.0000000000002621","pmid":"40729307","tags":["semaglutide","glp1-receptor-agonists","hormones-endocrine","reproductive-health"],"studyType":"case-report","evidenceStrength":"very-low","keyFinding":"A 51-year-old woman on oral estrogen for menopausal symptoms experienced worsening hot flashes and mood changes during semaglutide dose titration. Symptoms resolved when semaglutide titration was slowed.","whyItMatters":"GLP-1 drugs slow stomach emptying, which could reduce absorption of oral medications like estrogen. Clinicians should be aware of this potential drug interaction, especially during dose escalation.","specificNumbers":"Single patient, age 51, postmenopausal. Worsening vasomotor symptoms during semaglutide dose titration. Resolution after slowing titration schedule.","methodology":"Single case report with literature review on GLP-1 receptor agonist effects on gastric emptying and oral drug absorption.","limitations":"Single case. No plasma estrogen levels measured to confirm reduced absorption. Temporal association does not prove causation. Other factors could explain symptom worsening."},{"rthcId":"RPEP-12966","title":"Oxytocin can ameliorate social deficits and brain developmental impairments in a rat model of early life excessive screen time exposure.","authors":"Parsa, Mozhan; Mansouri, Monireh; Pouretemad, Hamidreza","year":2025,"journal":"Brain research bulletin, 228, 111419","doi":"10.1016/j.brainresbull.2025.111419","pmid":"40473077","tags":["oxytocin","neuropeptides-neuroscience","mental-health-psychiatry"],"studyType":"animal-study","evidenceStrength":"low","keyFinding":"Intranasal oxytocin reversed social deficits, hyperactivity, and brain structure changes caused by excessive screen exposure in rats. It restored amygdala and anterior cingulate cortex abnormalities.","whyItMatters":"Excessive screen time in early life is linked to autism-like behaviors. This study suggests oxytocin could reverse these effects by normalizing brain development, though this was tested only in rats.","specificNumbers":"EAVS exposure PND 12-35. Intranasal oxytocin 0.8 IU/kg from PND 21-35. Behavioral testing PND 50-55. Changes observed in amygdala and anterior cingulate cortex volume and neuron number.","methodology":"Neonatal rats exposed to excessive audiovisual stimulation. Treated with intranasal oxytocin. Assessed behavior (social interaction, repetitive behavior, locomotion, anxiety) and 3D brain structure at adolescence.","limitations":"Rat model of screen exposure is artificial. Audiovisual stimulation in rats does not replicate human screen use. Oxytocin dosing and timing may not translate. Only adolescent outcomes measured."},{"rthcId":"RPEP-12967","title":"The Impact and Safety of GLP-1 Agents and Breast Cancer.","authors":"Parsons, Kayla; Montalvo, Mateo; Fischbach, Neal; Taylor, Melissa; Alfaro, Salome; Lustberg, Maryam","year":2025,"journal":"Cancer medicine, 14(12), e70932","doi":"10.1002/cam4.70932","pmid":"40552446","tags":["glp1-receptor-agonists","cancer-oncology","obesity-weight-management"],"studyType":"narrative-review","evidenceStrength":"moderate","keyFinding":"GLP-1 receptor agonists may reduce breast cancer risk through weight loss and direct anti-tumor mechanisms. Preclinical studies show GLP-1 drugs can inhibit breast cancer cell proliferation, though clinical data are limited.","whyItMatters":"Obesity increases breast cancer risk and worsens outcomes. If GLP-1 drugs reduce cancer risk beyond just weight loss, they could play a dual role in high-risk obese women.","specificNumbers":"Obesity prevalence doubled since 1990. By 2022, 44% of women overweight, 18% obese. 2.2 million new breast cancer cases in 2020. Reviews behavioral, surgical, and pharmacological weight interventions.","methodology":"Comprehensive literature review (1996-2024) across PubMed, Medline, Web of Science. Included epidemiological data, systematic reviews, meta-analyses, clinical trials, and preclinical mechanistic studies.","limitations":"Review article. Direct evidence of GLP-1 drugs reducing breast cancer incidence is lacking. Preclinical anti-tumor effects may not translate to clinical benefit. Confounding by indication in observational data."},{"rthcId":"RPEP-12968","title":"Mechanisms and treatment of obesity-related hypertension-Part 2: Treatments.","authors":"Parvanova, Aneliya; Abbate, Manuela; Reseghetti, Elia; Ruggenenti, Piero","year":2025,"journal":"Clinical kidney journal, 18(3), sfaf035","doi":"10.1093/ckj/sfaf035","pmid":"40130230","tags":["semaglutide","tirzepatide","glp1-receptor-agonists","cardiovascular-health","obesity-weight-management"],"studyType":"narrative-review","evidenceStrength":"moderate","keyFinding":"Second-generation incretin drugs (semaglutide, tirzepatide) lower blood pressure more effectively than first-generation anti-obesity drugs. Tirzepatide, as a dual GLP-1/GIP agonist, shows the strongest blood pressure reduction alongside weight loss.","whyItMatters":"Obesity-related hypertension is common and inadequately addressed by current guidelines. Weight-centric treatment with newer GLP-1 drugs may simultaneously control weight and blood pressure.","specificNumbers":"Reviews efficacy of orlistat, phentermine/topiramate, naltrexone/bupropion (first-generation) vs liraglutide, semaglutide, tirzepatide (second-generation). Tirzepatide as dual GLP-1/GIP co-agonist discussed.","methodology":"Narrative review of treatments for obesity-related hypertension, focusing on the role of incretin receptor agonists.","limitations":"Narrative review. No head-to-head trials of anti-obesity drugs specifically for hypertension outcomes. Blood pressure benefits may be partly mediated by weight loss rather than direct drug effects."},{"rthcId":"RPEP-12969","title":"Calcitonin gene-related peptide (CGRP) in the pathophysiology of gastrointestinal disorders - A key mediator in the gut-brain axis.","authors":"Pascual-Mato, Marta; Gárate Viñas, Gabriel; Muñoz San Martín, María; González-Quintanilla, Vicente; Crespo, Javier; Rivero Tirado, Montserrat; Pascual Gómez, Julio","year":2025,"journal":"Revista espanola de enfermedades digestivas, 117(10), 572-578","doi":"10.17235/reed.2025.11310/2025","pmid":"40418063","tags":["cgrp","neuropeptides-neuroscience","gastrointestinal-health","pain-management"],"studyType":"narrative-review","evidenceStrength":"moderate","keyFinding":"CGRP, especially the beta isoform in the gut nervous system, plays a protective role in the gut-brain axis. It is involved in diverticular disease, infectious diarrhea, and inflammatory bowel disease.","whyItMatters":"CGRP is best known as a migraine molecule, but it also protects the gut. Blocking CGRP for migraines might have unintended gut consequences. Understanding its dual role is important for safe treatment.","specificNumbers":"Reviews CGRP role in migraine (first biomarker), diverticular disease, acute infectious diarrhea, and inflammatory bowel disease. Distinguishes alpha-CGRP (neuronal) from beta-CGRP (enteric).","methodology":"Narrative review of basic and clinical evidence on CGRP in the gut-brain axis, with emphasis on recent experimental and clinical data.","limitations":"Narrative review. Most gut-CGRP evidence is preclinical. Clinical data on CGRP migraine drug effects on GI health are limited."},{"rthcId":"RPEP-12970","title":"PMAP-37: A versatile cathelicidin for neutralizing bacteria and viruses.","authors":"Pashaie, Fatemeh; Benne, Naomi; Holzapfel, Philippa I P; Veenendaal, Tineke; Bikker, Floris J; Heesterbeek, Dani A C; Broere, Femke; Veldhuizen, Edwin J A","year":2025,"journal":"Microbial pathogenesis, 204, 107568","doi":"10.1016/j.micpath.2025.107568","pmid":"40228754","tags":["antimicrobial-peptides","inflammation-immunity","infectious-disease"],"studyType":"in-vitro","evidenceStrength":"low","keyFinding":"PMAP-37, a pig cathelicidin, killed both Gram-positive and Gram-negative bacteria at low concentrations, neutralized LPS-induced inflammation, and showed antiviral activity. It disrupted bacterial membranes within 5 minutes.","whyItMatters":"PMAP-37 is an understudied member of the pig cathelicidin family that works against both bacteria and viruses. Its rapid membrane disruption and anti-inflammatory effects make it a versatile antimicrobial candidate.","specificNumbers":"MBC: 2.5 mcM for B. globigii (Gram-positive), 5 mcM for E. coli (Gram-negative). Outer and inner membrane permeabilization within 5 min. Dose-dependent neutralization of LPS, Lipid A, and LTA-induced NO production.","methodology":"In vitro antimicrobial activity testing, membrane permeabilization assays, LPS binding analysis by flow cytometry, zeta potential analysis, and antiviral testing.","limitations":"In vitro study only. No in vivo efficacy or toxicity data. Antiviral mechanisms not fully characterized. Translation to therapeutic use requires extensive further testing."},{"rthcId":"RPEP-12971","title":"Subcutaneous weekly semaglutide with automated insulin delivery in type 1 diabetes: a double-blind, randomized, crossover trial.","authors":"Pasqua, Melissa-Rosina; Tsoukas, Michael A; Kobayati, Alessandra; Aboznadah, Wedyan; Jafar, Adnan; Haidar, Ahmad","year":2025,"journal":"Nature medicine, 31(4), 1239-1245","doi":"10.1038/s41591-024-03463-z","pmid":"39794615","tags":["semaglutide","glp1-receptor-agonists","diabetes-glucose-metabolism"],"studyType":"randomized-controlled-trial","evidenceStrength":"moderate","keyFinding":"Semaglutide added to automated insulin delivery in type 1 diabetes increased time in glucose target range by 4.8 percentage points without increasing hypoglycemia. Two cases of euglycemic ketosis occurred.","whyItMatters":"Type 1 diabetes management remains challenging even with insulin pumps. This is the first blinded trial showing semaglutide can improve glucose control in T1D when paired with automated insulin delivery.","specificNumbers":"28 randomized, 24 completed. Time in range (3.9-10.0 mmol/L) increased 4.8 percentage points (SD 7.6, P = 0.006). No increase in time below 3.9 (P = 0.19) or 3.0 mmol/L (P = 0.65). No DKA or severe hypoglycemia. 2 euglycemic ketosis episodes. Max dose 1 mg.","methodology":"Randomized, double-blind, crossover trial. Semaglutide titrated up to 1 mg over 11 weeks, then 4 weeks on automated insulin delivery. Primary endpoint: time in target glucose range during last 4 weeks.","limitations":"Very small (28 randomized, 24 completed). Short treatment period (15 weeks total). Crossover design may have carryover effects. Euglycemic ketosis is a safety concern needing longer-term data."},{"rthcId":"RPEP-12972","title":"Conformational ligand-directed targeting of calcium-dependent receptors in acute trauma.","authors":"Pasqualini, Renata; Markosian, Christopher; Staquicini, Daniela I; Dobroff, Andrey S; Dodero-Rojas, Esteban; Whitford, Paul C; Barbu, E Magda; Bronk, Julianna K; Cardó-Vila, Marina; Christianson, Dawn R; Dias-Neto, Emmanuel; Driessen, Wouter H P; Guzman-Rojas, Liliana; Marchiò, Serena; Nunes, Diana N; de Oliveira, Francislon S; Ozawa, Michael G; Proneth, Bettina; Rangel, Roberto; Smith, Tracey L; Souza, Glauco R; Staquicini, Fernanda I; Tang, Fenny H F; Baze, Wallace B; Setubal, João C; Burns, John W; Dubick, Michael A; Gelovani, Juri G; Batchinsky, Andriy I; Mogford, Jon E; Wade, Charles E; Holcomb, John B; Burley, Stephen K; Onuchic, José N; Arap, Wadih","year":2025,"journal":"Med (New York, N.Y.), 6(7), 100638","doi":"10.1016/j.medj.2025.100638","pmid":"40609540","tags":["drug-delivery-systems","tissue-engineering-regeneration"],"studyType":"animal-study","evidenceStrength":"low","keyFinding":"Screening a peptide library in a pig trauma model revealed that nearly all ligand targets were calcium-dependent proteins exposed during injury. Homing peptides specifically bound to trauma sites on PET/MRI and SPECT/CT imaging.","whyItMatters":"Trauma has few injury-specific molecular targets. This discovery of calcium-dependent proteins exposed during injury could enable targeted drug delivery or imaging at trauma sites.","specificNumbers":"Porcine model: compound femur fracture with hemorrhagic shock. Validated in corresponding rat model. PET/MRI and SPECT/CT imaging confirmed specific homing. Nearly all targets were calcium-dependent proteins.","methodology":"Peptide library screening in porcine trauma model. Bioinformatics for motif discovery. Affinity purification of candidate receptors. In silico and in vitro calcium association studies. In vivo homing with PET/MRI and SPECT/CT. Molecular dynamics simulations.","limitations":"Animal models only (pig and rat). Trauma models do not fully replicate human injury complexity. Peptide stability and pharmacokinetics in humans unknown. Very early-stage research."},{"rthcId":"RPEP-12973","title":"Effects of glucagon-like PEPTIDE-1 receptor agonists on incidence of hepatocellular carcinoma and liver decompensation in patients with diabetes: A systematic review and META-analysis.","authors":"Pasta, Andrea; Facciorusso, Antonio; Plaz Torres, Maria Corina; Giannini, Edoardo G; Sacco, Rodolfo","year":2025,"journal":"European journal of clinical investigation, 55(6), e70000","doi":"10.1111/eci.70000","pmid":"39937048","tags":["glp1-receptor-agonists","liver-health","cancer-oncology","diabetes-glucose-metabolism"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"GLP-1 receptor agonists were associated with a 58% reduction in hepatocellular carcinoma risk in patients with type 2 diabetes. The effect was strongest in patients with cirrhosis. Liver decompensation trends were not statistically significant.","whyItMatters":"Liver cancer is a major complication of diabetes-related liver disease. A 58% risk reduction, if confirmed in prospective trials, would add cancer prevention to the growing list of GLP-1 drug benefits.","specificNumbers":"Over 641,377 patients analyzed. 58% reduction in HCC risk with GLP-1RA use. Strongest in patients with cirrhosis. Trend toward reduced liver decompensation but not statistically significant.","methodology":"Systematic review and meta-analysis of studies evaluating GLP-1RA effects on HCC and liver decompensation in type 2 diabetes patients.","limitations":"Observational studies subject to confounding. GLP-1 users may differ systematically from non-users. Causation cannot be established. Heterogeneity across studies likely."},{"rthcId":"RPEP-12974","title":"The endocrine disruptor chlorpyrifos alters hypothalamic Npy and Agrp expression via ERβ-dependent regulation in vitro and in vivo.","authors":"Pastorino, Monica; Desiderio, Antonella; Perrella, Erica; Campitelli, Michele; Nigro, Cecilia; Peluso, Teresa; De Felice, Mario; Ambrosino, Concetta; Beguinot, Francesco; Miele, Claudia; Raciti, Gregory Alexander","year":2025,"journal":"Frontiers in endocrinology, 16, 1726498","doi":"10.3389/fendo.2025.1726498","pmid":"41613962","tags":["neuropeptides-neuroscience","obesity-weight-management","hormones-endocrine"],"studyType":"animal-study","evidenceStrength":"low","keyFinding":"The pesticide chlorpyrifos increased hunger-driving neuropeptides (NPY and AgRP) in mouse brain cells and hypothalami through estrogen receptor beta signaling. This suggests a central mechanism for pesticide-linked obesity.","whyItMatters":"Chlorpyrifos is a widely used pesticide linked to metabolic problems. This study shows it can directly alter brain hunger signals, potentially contributing to obesity through central nervous system disruption.","specificNumbers":"In vitro: 1 pM CPF in mHypoE-N46 cells, acute (4 h) and chronic (6-day) exposure. In vivo: CD-1 mice, 10 mg/kg/day CPF from conception to 6 months on standard diet. Measured NPY and AgRP gene/protein expression and secretion.","methodology":"In vitro hypothalamic cell culture (mHypoE-N46) with CPF treatment. In vivo hypothalamic tissue analysis from chronically exposed mice. qPCR, western blotting, ELISA. Pharmacological ER-alpha and ER-beta antagonists.","limitations":"Mouse model. CPF dose (10 mg/kg/day) may not reflect typical human exposure. In vitro cell line does not replicate full hypothalamic complexity. Only orexigenic peptides studied."},{"rthcId":"RPEP-12975","title":"Recent advances in the therapeutics and modes of action of a range of agents used to treat ulcerative colitis and related inflammatory conditions.","authors":"Patel, Alka; Jain, Parag; Ajazuddin","year":2025,"journal":"Inflammopharmacology, 33(9), 4965-4996","doi":"10.1007/s10787-025-01906-8","pmid":"40815427","tags":["glp1-receptor-agonists","gastrointestinal-health","inflammation-immunity","drug-delivery-systems"],"studyType":"narrative-review","evidenceStrength":"moderate","keyFinding":"Protein-peptide complexes demonstrated ability to heal epithelial barriers, suppress pro-inflammatory cytokines (TNF-α, IL-13, IL-17), and restore gut microbiota balance in preclinical UC models.","whyItMatters":"Current UC treatments often fail to achieve long-term remission or fully repair the gut barrier. Peptide therapies offer a more targeted approach with lower systemic toxicity, potentially filling a critical gap in UC management.","specificNumbers":"Reviews GLP-2 analogs, antimicrobial peptides, and other protein-peptide complexes. Covers tight junction repair, epithelial proliferation, immune cell targeting, and microbiome reconstitution strategies.","methodology":"Literature review and synthesis of recent data on molecular pathophysiology, clinical pharmacology, and drug delivery advances for peptide-based UC therapies.","limitations":"Most evidence comes from preclinical models rather than human clinical trials. Long-term safety, manufacturing scalability, and cost-effectiveness of peptide therapies remain to be established."},{"rthcId":"RPEP-12976","title":"Beyond Natriuretic Peptides: Corin and Furin As Phenotype-Specific Biomarkers and Therapeutic Gatekeepers in Heart Failure.","authors":"Patel, Dhruvil Vinaybhai; Patel, Sanket; Acharya, Sankalp; Raol, Karanrajsinh","year":2025,"journal":"Current heart failure reports, 22(1), 41","doi":"10.1007/s11897-025-00732-x","pmid":"41264150","tags":["natriuretic-peptides","heart-failure","cardiovascular-health"],"studyType":"narrative-review","evidenceStrength":"moderate","keyFinding":"Corin and furin show altered expression across different heart failure phenotypes, offering mechanistic insight into disease progression, though their diagnostic performance remains modest compared to BNP and NT-proBNP.","whyItMatters":"Understanding the upstream enzymes that activate protective heart peptides could lead to new diagnostic tools and targeted therapies for heart failure, moving beyond current one-size-fits-all approaches.","specificNumbers":"Reviews corin (cardiac-restricted serine protease) and furin (ubiquitous convertase). Both activate pro-ANP and pro-BNP. Diagnostic performance shows modest sensitivity and specificity compared to BNP/NT-proBNP.","methodology":"Narrative review synthesizing published studies on the physiological and pathological roles of corin and furin in heart failure, evaluating their biomarker potential.","limitations":"Corin and furin biomarker performance has not yet shown clear incremental benefit over existing markers in clinical settings. Most evidence is from observational studies, not prospective clinical trials."},{"rthcId":"RPEP-12977","title":"Dynamic Nanopeptide Assemblies for Trans-Tympanic Drug Delivery.","authors":"Patel, Evan A; Shah, Swapnil V; Poulson, Trevor A; Fry, H Christopher; Jagasia, Ashok A","year":2025,"journal":"International journal of nanomedicine, 20, 9301-9310","doi":"10.2147/IJN.S507576","pmid":"40727582","tags":["drug-delivery-systems","peptide-synthesis-chemistry","infectious-disease"],"studyType":"in-vitro","evidenceStrength":"very-low","keyFinding":"The peptide amphiphile hydrogel successfully transitioned from 1D nanofiber networks to 0D micelles, functioning as cell-penetrating peptides while providing temporal control of ciprofloxacin release over 48 hours. The formulation was non-cytotoxic to epidermal keratinocytes.","whyItMatters":"Ear infections are one of the most common childhood illnesses, often requiring invasive procedures for treatment. A non-invasive peptide-based system that can deliver drugs through the eardrum could transform ear infection treatment, reducing the need for surgery and improving patient comfort.","specificNumbers":"Peptide amphiphile c16-AHL3K3-CO2H at 0.1-1 wt%. Ciprofloxacin at 1 wt%. Drug release measured over 48 hours. Cytotoxicity tested on epidermal keratinocytes at various concentrations.","methodology":"Preliminary in vitro study: Fmoc solid-phase peptide synthesis, drug release simulation using porous insert microplates over 48 hours, keratinocyte viability assays for cytotoxicity, and laser scanning confocal microscopy for membrane penetration visualization.","limitations":"Preliminary in vitro study only. No in vivo testing or animal models. Eardrum penetration was simulated with porous inserts, not actual tympanic membrane. Drug release kinetics and therapeutic concentrations at the target site need validation. Long-term stability not assessed."},{"rthcId":"RPEP-12978","title":"Comparative Effectiveness of Semaglutide, Liraglutide, Orlistat, and Phentermine for Weight Loss in Obese Individuals: A Systematic Review.","authors":"Patel, Jay P; Hardaswani, Daksh; Patel, Jaykumar; Saiyed, Faizanali; Goswami, Rushita J; Saiyed, Taskin I; Patel, Harshkumar; Amin, Trishul H","year":2025,"journal":"Cureus, 17(3), e80321","doi":"10.7759/cureus.80321","pmid":"40206909","tags":["semaglutide","glp1-receptor-agonists","obesity-weight-management"],"studyType":"systematic-review","evidenceStrength":"moderate","keyFinding":"All four agents provide weight loss benefits through distinct mechanisms. GLP-1 agonists (semaglutide, liraglutide) show superior efficacy but cause GI side effects. Orlistat reduces fat absorption with GI discomfort. Phentermine suppresses appetite but has dependency potential. Emerging dual/triple agonists show promise.","whyItMatters":"With multiple obesity medications now available, clinicians need comparative data to match the right drug to each patient. This review provides a comprehensive comparison to guide personalized treatment selection based on efficacy needs, side effect tolerance, and comorbidity profiles.","specificNumbers":"Compares semaglutide, liraglutide, orlistat, phentermine, plus emerging agents: setmelanotide, amycretin, retatrutide, cagrilintide, and cotadutide. Reviews mechanisms, dosing, efficacy, safety, and comorbidity effects.","methodology":"Systematic literature review comparing mechanisms, dosing, efficacy, safety profiles, and comorbidity impact of semaglutide, liraglutide, orlistat, phentermine, and emerging obesity agents.","limitations":"Literature review without meta-analysis or quantitative pooling. Head-to-head trial data is limited for many comparisons. Emerging agents have less mature evidence. Long-term comparative data is scarce."},{"rthcId":"RPEP-12979","title":"Euglycemic Diabetic Ketoacidosis in the Setting of Dulaglutide Use.","authors":"Patel, Niyati; Reddy, Anvit; Romero, Kaitlyn N; Reddy, Pramod","year":2025,"journal":"Cureus, 17(4), e82143","doi":"10.7759/cureus.82143","pmid":"40357083","tags":["glp1-receptor-agonists","diabetes-glucose-metabolism"],"studyType":"case-report","evidenceStrength":"very-low","keyFinding":"Dulaglutide re-initiation at a higher dose triggered euglycemic DKA presenting with GI symptoms and weakness. Normal blood glucose levels made diagnosis challenging. Resolved with insulin drip and IV fluids.","whyItMatters":"As GLP-1 drug prescriptions surge, clinicians must be aware that euglycemic DKA—though rare—can occur with these medications, not just with SGLT2 inhibitors. The non-specific symptoms and normal glucose levels make this easy to miss, potentially life-threatening if untreated.","specificNumbers":"Single patient with T2DM. Euglycemic DKA after re-initiation of dulaglutide at higher dose. Presented with GI symptoms and weakness. Resolved with insulin drip and IV fluids.","methodology":"Single case report with clinical presentation, laboratory findings, and treatment outcome documentation.","limitations":"Single case report cannot establish causation or frequency. Other contributing factors may have been present. No rechallenge was attempted. Rare adverse event reporting may be subject to publication bias."},{"rthcId":"RPEP-12980","title":"Therapeutic Potential of GLP-1 Receptor Agonists in Heart Failure with Preserved Ejection Fraction (HFpEF) in Obese Patients.","authors":"Patel, Ravi; Kokori, Emmanuel; Olatunji, Gbolahan; Adejumo, Faith Adedayo; Ukah, Joan Dumebi; Babalola, Adetola Emmanuel; Ndakotsu, Andrew; Abraham, Israel Charles; Aderinto, Nicholas","year":2025,"journal":"Current heart failure reports, 22(1), 17","doi":"10.1007/s11897-025-00704-1","pmid":"40366488","tags":["semaglutide","tirzepatide","glp1-receptor-agonists","heart-failure","obesity-weight-management"],"studyType":"narrative-review","evidenceStrength":"strong","keyFinding":"In STEP-HFpEF and SUMMIT trials, semaglutide and tirzepatide achieved 13.3% and 13.9% weight reduction, 21.5m and 26m improvements in 6MWD, 19.5 and 16.6 point KCCQ-CSS improvements, and 38.8% and 43.5% CRP reductions in obese HFpEF patients.","whyItMatters":"HFpEF in obesity has limited treatment options and growing prevalence. GLP-1 drugs addressing both the cardiac symptoms and the underlying obesity represents a paradigm shift in managing this challenging condition.","specificNumbers":"Semaglutide: 13.3% weight loss, +21.5m 6MWD, +19.5 KCCQ-CSS, -38.8% CRP. Tirzepatide: 13.9% weight loss, +26m 6MWD, +16.6 KCCQ-CSS, -43.5% CRP. From STEP-HFpEF and SUMMIT trials.","methodology":"Narrative review synthesizing clinical trial data including STEP-HFpEF and SUMMIT studies on GLP-1RAs for HFpEF in obesity.","limitations":"Short trial durations. Limited population diversity. No long-term hospitalization or mortality data yet. Benefits may be partly mediated by weight loss rather than direct cardiac effects."},{"rthcId":"RPEP-12981","title":"Larotrectinib-associated withdrawal symptoms resolved following initiation of GLP-1 receptor agonist: a case report.","authors":"Patel, Reema; Deeken, John F","year":2025,"journal":"Cancer chemotherapy and pharmacology, 95(1), 102","doi":"10.1007/s00280-025-04829-x","pmid":"41125972","tags":["semaglutide","glp1-receptor-agonists","cancer-oncology","pain-management"],"studyType":"case-report","evidenceStrength":"very-low","keyFinding":"Long-standing twice-daily withdrawal symptoms from larotrectinib (myalgias, arthralgias, photosensitivity occurring 30-45 min before doses) completely resolved after semaglutide initiation in a patient with >7 years of TRK inhibitor therapy.","whyItMatters":"About one-third of patients on TRK inhibitors experience withdrawal-like symptoms that significantly impact quality of life. If GLP-1 agonists can reliably resolve these symptoms, it would improve tolerability of an important cancer therapy.","specificNumbers":"Patient: 35-year-old male with metastatic ETV6-NTRK3 parotid gland cancer. Larotrectinib for 7+ years with complete response. Daily myalgias and arthralgias 30-45 min before next dose. Complete resolution after starting semaglutide.","methodology":"Single case report documenting clinical timeline of larotrectinib withdrawal symptoms and resolution with semaglutide.","limitations":"Single case report. No controlled comparison. Cannot establish causation—symptoms may have resolved coincidentally. Mechanism is speculative. Reproducibility unknown."},{"rthcId":"RPEP-12982","title":"GLP-1 receptor agonists and alcohol use disorder: a systematic review.","authors":"Patel, Sheel; Blaney, Hanna; Nassar, Sarah; Singal, Ashwani K","year":2025,"journal":"Alcohol and alcoholism (Oxford, Oxfordshire), 61(1)","doi":"10.1093/alcalc/agaf069","pmid":"41273789","tags":["semaglutide","glp1-receptor-agonists","mental-health-psychiatry","addiction-substance-use"],"studyType":"systematic-review","evidenceStrength":"moderate","keyFinding":"Semaglutide reduced alcohol use; dulaglutide lowered intake in current drinkers; exenatide showed no significant effect on heavy drinking days. Three RCTs reviewed (n=48-151).","whyItMatters":"Alcohol use disorder has few effective pharmacotherapies. If GLP-1 drugs—already widely prescribed for diabetes and obesity—also reduce alcohol consumption, they could address a major unmet medical need and benefit patients with overlapping conditions.","specificNumbers":"Three RCTs reviewed (n = 48-151). Semaglutide reduced alcohol use. Dulaglutide lowered intake in current drinkers. Exenatide had no significant effect on heavy drinking days.","methodology":"Systematic review of three randomized controlled trials (n=48-151) examining GLP-1 receptor agonists for alcohol use outcomes.","limitations":"Only three small RCTs available. Sample sizes were small (48-151). Not all GLP-1 drugs showed effects. Alcohol outcomes were not always primary endpoints. Larger, dedicated trials needed."},{"rthcId":"RPEP-12983","title":"Emerging Frontiers in GLP-1 Therapeutics: A Comprehensive Evidence Base (2025).","authors":"Patel, Shikha; Niazi, Sarfaraz K","year":2025,"journal":"Pharmaceutics, 17(8)","doi":"10.3390/pharmaceutics17081036","pmid":"40871057","tags":["glp1-receptor-agonists","diabetes-glucose-metabolism","obesity-weight-management","cardiovascular-health","neuropeptides-neuroscience"],"studyType":"systematic-review","evidenceStrength":"strong","keyFinding":"GLP-1 RAs achieve HbA1c reductions of 1.5-2.0%, weight loss of 7-24%, and 14-20% MACE reduction. Pleiotropic mechanisms include mitochondrial function enhancement, anti-inflammatory effects, and cellular quality control improvement. Emerging applications span neurology, dermatology, respiratory, addiction, and autoimmune fields.","whyItMatters":"GLP-1 drugs are arguably the most important new drug class in decades. This review captures the full scope of their therapeutic potential, helping clinicians understand applications far beyond the original diabetes indication.","specificNumbers":"HbA1c reduction: 1.5-2.0%. Weight loss: 7-24%. MACE reduction: 14-20%. Reviews enhanced mitochondrial function, anti-inflammatory actions, cellular quality control.","methodology":"Systematic literature search of PubMed, Embase, Cochrane Library, and ClinicalTrials.gov through May 2025.","limitations":"Broad review may lack depth on specific emerging applications. Many emerging indications are based on preclinical or early-phase data. Systematic but not a formal meta-analysis."},{"rthcId":"RPEP-12984","title":"Mediterranean diet adherence and tirzepatide: real-world evidence on adiposity indices and insulin resistance beyond weight loss.","authors":"Paternò, Valentina; Geraci, Giulio; Piticchio, Tommaso; Le Moli, Rosario; Burgio, Stefano; Costanzo, Gabriele; Sambataro, Gianluca; Baratta, Roberto; Barbagallo, Federica; Pallotti, Francesco","year":2025,"journal":"Frontiers in endocrinology, 16, 1700894","doi":"10.3389/fendo.2025.1700894","pmid":"41613958","tags":["tirzepatide","glp1-receptor-agonists","obesity-weight-management","diabetes-glucose-metabolism"],"studyType":"observational","evidenceStrength":"low","keyFinding":"After 3 months of tirzepatide, significant reductions in weight, BMI, WC, WtHR, BRI, and VAI (all p<0.05). PREDIMED scores increased +3.2 points (p<0.001). Higher Mediterranean diet adherence independently associated with lower insulin, improved HOMA, and greater VAI reduction.","whyItMatters":"Clinical trials of GLP-1 drugs rarely account for diet quality. This study provides first evidence that what patients eat while on tirzepatide matters—Mediterranean diet adherence specifically enhances visceral fat reduction and metabolic improvement beyond drug effects alone.","specificNumbers":"53 patients with BMI >= 27-30. Tirzepatide 2.5 mg/week for 1 month then 5.0 mg/week. 3-month follow-up. Assessed BMI, waist circumference, WtHR, BRI, ABSI, VAI. PREDIMED score for diet quality. Significant reductions in weight and adiposity indices.","methodology":"Prospective real-world study of 53 overweight/obese patients on tirzepatide (2.5→5 mg/week) with Mediterranean diet counseling, assessed at baseline and 3 months with anthropometric, adiposity, and biochemical measures.","limitations":"Small sample (n=53). No control group without Mediterranean diet. Short 3-month follow-up. Observational design cannot confirm causation between diet and enhanced outcomes. Self-reported dietary adherence."},{"rthcId":"RPEP-12985","title":"Unleashing the Antiviral Potential of Stapled Peptides: A New Frontier in Combating Human Neurotropic Viral Infections.","authors":"Patil, Sanskruti; Rahangdale, Rakesh; Pasupuleti, Mukesh; Santhoshkumar, Puttur; Hariharapura, Raghu Chandrashekar","year":2025,"journal":"Microbial biotechnology, 18(9), e70221","doi":"10.1111/1751-7915.70221","pmid":"40955200","tags":["peptide-synthesis-chemistry","infectious-disease","drug-delivery-systems"],"studyType":"narrative-review","evidenceStrength":"moderate","keyFinding":"Peptide stapling via hydrocarbon staples, lactam bridges, and metal-coordination bonds enhances peptide stability, bioavailability, cellular penetration, and target binding affinity for antiviral applications against neurotropic viruses including HSV and influenza.","whyItMatters":"Neurotropic viral infections cause devastating diseases with limited treatment options. Stapled peptides could overcome the pharmacological limitations of natural antiviral peptides, creating a new class of drugs for brain-targeting viruses that resist current therapies.","specificNumbers":"Reviews stapling techniques for peptides targeting HSV, VZV, HIV, poliovirus, enteroviruses, parechovirus, West Nile virus, and Japanese encephalitis virus.","methodology":"Narrative review of stapling techniques and their application to antiviral peptide development, focusing on neurotropic viral targets.","limitations":"Review of early-stage research; most stapled antiviral peptides are in preclinical development. No clinical trial data available. Manufacturing complexity and cost of stapled peptides may limit scalability."},{"rthcId":"RPEP-12986","title":"A double-blind, placebo-controlled trial of exenatide for the treatment of olanzapine-related weight gain in obese and overweight adults.","authors":"Patino, Luis R; Strawn, Jeffrey R; Adler, Caleb M; Blom, Thomas J; Welge, Jeffrey A; DelBello, Melissa P","year":2025,"journal":"Journal of affective disorders, 382, 116-122","doi":"10.1016/j.jad.2025.04.046","pmid":"40203970","tags":["glp1-receptor-agonists","mental-health-psychiatry","obesity-weight-management"],"studyType":"randomized-controlled-trial","evidenceStrength":"moderate","keyFinding":"Exenatide vs placebo over 16 weeks: -0.5 kg (-0.6%) vs +2.6 kg (+2.8%), both p<0.01. Exenatide was well-tolerated. No clinically meaningful differences in mood or psychotic symptoms between groups.","whyItMatters":"Olanzapine is one of the most effective antipsychotics but causes severe weight gain that leads to metabolic syndrome, diabetes, and medication discontinuation. An effective, psychiatrically safe weight management option could improve both physical health and medication adherence in this vulnerable population.","specificNumbers":"Exenatide: -0.5 kg (-0.6%) vs placebo: +2.6 kg (+2.8%), both P < 0.01. 16-week double-blind trial. Most common side effects: GI symptoms and headaches. No clinically meaningful changes in mood or psychotic symptoms.","methodology":"Randomized, double-blind, placebo-controlled trial (NCT00845507) in adults with stable major mood or psychotic disorders on olanzapine, treated for 16 weeks.","limitations":"Relatively small sample size and short 16-week duration. Only studied exenatide (less potent than semaglutide). Only studied olanzapine; results may not generalize to other antipsychotics. Primarily assessed weight prevention rather than weight loss."},{"rthcId":"RPEP-12987","title":"Peptide receptor radionuclide therapy in malignant insulinoma.","authors":"Pattison, David A; Kong, Grace; Akhurst, Timothy; Burge, Matthew; Chiang, Cherie; Hofman, Michael S; Hung, Te-Jui; Love, Amanda; Michael, Michael; Okano, Satomi; Ravi Kumar, Aravind S; Sachithanandan, Nirupa; Wyld, David; Hicks, Rodney J","year":2025,"journal":"Endocrine-related cancer, 32(6)","doi":"10.1530/ERC-25-0018","pmid":"40424062","tags":["peptide-receptor-radionuclide-therapy","neuroendocrine-tumors","diabetes-glucose-metabolism"],"studyType":"retrospective-cohort","evidenceStrength":"moderate","keyFinding":"PRRT with Lu-177 DOTATATE resolved hypoglycemia in 93% of patients (14/15) after a median of 2.5 months, with median overall survival of 50.1 months and successful re-treatment in all recurrence cases.","whyItMatters":"Malignant insulinoma is life-threatening primarily because of uncontrollable hypoglycemia. PRRT addresses both the tumor and the dangerous metabolic symptoms, providing a critical treatment option for patients who have exhausted other therapies.","specificNumbers":"15 patients (7 female, median age 60). Median 7 cycles (range 1-15), median cumulative 42 GBq (range 4-117). 93% (14/15) had hypoglycemia resolution at median 2.5 months. Recurred in 7/14 at median 17.7 months. Recurrence group: more G3 (57% vs 0%), longer time to resolution (3.0 vs 0.5 months).","methodology":"Retrospective review of 15 consecutive malignant insulinoma patients treated with PRRT at two Australian neuroendocrine tumor centers from 2004 to 2022.","limitations":"Retrospective design, small sample size (n=15), single-arm without comparison group. Patient heterogeneity in tumor grade and treatment protocols. Hypoglycemia flare during treatment required hospitalization in nearly half of patients."},{"rthcId":"RPEP-12988","title":"A Case Series on the Efficacy of the Pharmacological Treatment of Lipedema: The Italian Experience with Exenatide.","authors":"Patton, Laura; Reverdito, Valeria; Bellucci, Alessandra; Bortolon, Micaela; Macrelli, Annalisa; Ricolfi, Lorenzo","year":2025,"journal":"Clinics and practice, 15(7)","doi":"10.3390/clinpract15070128","pmid":"40710038","tags":["glp1-receptor-agonists","obesity-weight-management","skin-dermatology"],"studyType":"case-series","evidenceStrength":"very-low","keyFinding":"Exenatide reduced lipedema symptoms, evoked pain, and ultrasound-measured subcutaneous fat thickness in legs, abdomen, and arms, including in patients without weight loss.","whyItMatters":"Lipedema has no approved pharmacological treatment. This case series suggests GLP-1 drugs may address the disease directly — not just through weight loss — by targeting the metabolic dysfunction underlying abnormal fat accumulation.","specificNumbers":"5 women with lipedema and insulin resistance. Exenatide once weekly for 3-6 months. Reduced symptoms, pinch-test pain, and ultrasound-measured fat thickness at lower limbs, abdomen, and upper limbs. 4/5 had weight reduction.","methodology":"Case series of 5 women with lipedema and insulin resistance treated with once-weekly exenatide for 3-6 months, with assessment of anthropometric parameters, symptoms, clinical findings, and ultrasound-measured adipose tissue thickness.","limitations":"Very small case series (n=5) without a control group. Cannot distinguish between drug effects and lifestyle changes. Improvements may not be generalizable to all lipedema patients."},{"rthcId":"RPEP-12989","title":"An in silico vaccinomics strategy to develop multiepitope vaccine using essential hypothetical protein as a target against Brevundimonas subvibrioides: A combined subtractive proteomics and immunoinformatics approach.","authors":"Paul, Ishani; Roy, Alankar; Sarkar, Tista; Dutta, Shounak; Ray, Sujay","year":2025,"journal":"Microbial pathogenesis, 205, 107651","doi":"10.1016/j.micpath.2025.107651","pmid":"40334722","tags":["peptide-synthesis-chemistry","infectious-disease","inflammation-immunity"],"studyType":"computational","evidenceStrength":"very-low","keyFinding":"A multi-epitope vaccine candidate was designed using subtractive proteomics and immunoinformatics targeting essential hypothetical proteins of antibiotic-resistant B. subvibrioides.","whyItMatters":"Antibiotic resistance is rendering current treatments ineffective against Brevundimonas infections. A vaccine approach could prevent infections entirely, bypassing the resistance problem.","specificNumbers":"15 essential hypothetical proteins from DEG database. Multi-server functional annotation, physicochemical characterization, and non-homology analysis performed.","methodology":"In silico study combining subtractive proteomics (to identify essential non-human-homologous bacterial proteins) with immunoinformatics (to predict immunogenic epitopes and design a multi-epitope vaccine construct).","limitations":"Entirely computational — no laboratory validation, animal testing, or clinical data. The predicted immunogenicity and protective efficacy remain theoretical until experimentally confirmed."},{"rthcId":"RPEP-12990","title":"Heart Failure With Preserved Ejection Fraction and Low B-type Natriuretic Peptide: A Diagnostic Dilemma.","authors":"Paul, Tyler; Nadeem, Amin Ur Rehman; Naqvi, Syed M; Liu, Jason; Ali, Khaled A","year":2025,"journal":"Cureus, 17(4), e82602","doi":"10.7759/cureus.82602","pmid":"40395265","tags":["natriuretic-peptides","heart-failure","cardiovascular-health"],"studyType":"case-report","evidenceStrength":"very-low","keyFinding":"BNP and NT-proBNP levels may be normal in HFpEF patients due to reduced myocardial wall stress, increased peptide clearance, and medication effects, creating a significant diagnostic gap.","whyItMatters":"HFpEF is increasingly common, especially with rising obesity rates. If normal BNP levels falsely reassure clinicians, patients may not receive timely diagnosis and treatment for a serious condition.","specificNumbers":"BNP and NT-proBNP may be normal in HFpEF. Factors: obesity, reduced wall stress, enhanced NP clearance, NPR-C-mediated degradation. NT-proBNP levels vary by ethnicity. Normal ranges may miss HFpEF in patients under 75.","methodology":"Review article examining the diagnostic limitations of natriuretic peptide testing in HFpEF and factors contributing to false-negative results.","limitations":"Review article without new clinical data. The exact rate of false-negative BNP results in HFpEF is not precisely quantified."},{"rthcId":"RPEP-12991","title":"Combined RAS Modulation: The Effect on Plasma and Tissue Angiotensin Peptide Levels.","authors":"Paulis, L; Rajkovicova, R; Repova, K; Gubo, G; Barta, A; Poglitsch, M; Domenig, O; Andelova, N; Ferko, M; Pechanova, O; Simko, F","year":2025,"journal":"Physiological research, 74(Suppl 2), S205-S218","doi":null,"pmid":"41532628","tags":["cardiovascular-health","hormones-endocrine"],"studyType":"animal-study","evidenceStrength":"low","keyFinding":"Lisinopril produced the strongest antihypertensive effect; dual RAS blockade created complex angiotensin peptide profile changes but only modest additional blood pressure reduction in this low-RAS model.","whyItMatters":"Understanding why combined RAS blockade fails to improve outcomes despite better blood pressure control is critical for developing safer and more effective antihypertensive strategies.","specificNumbers":"SHR (spontaneously hypertensive rats). Tested lisinopril, olmesartan, aliskiren, and dual combinations. Lisinopril and olmesartan increased Ang I and Ang 1-7. Lisinopril suppressed Ang II while olmesartan increased it. Aliskiren reduced Ang II and Ang 1-7.","methodology":"Preclinical study in spontaneously hypertensive rats (SHR) measuring hemodynamics and circulating and tissue angiotensin peptide levels during single and dual RAS inhibitor treatment.","limitations":"Animal study in spontaneously hypertensive rats, which may not fully replicate human RAS physiology. The low-RAS setting of SHR may limit applicability to high-RAS forms of hypertension."},{"rthcId":"RPEP-12992","title":"A subpopulation of projections from the parabrachial nucleus to the central amygdala mediates itch.","authors":"Pavlenko, Darya; Ishida, Hirotake; Markan, Anika; Akiyama, Tasuku","year":2025,"journal":"Scientific reports, 15(1), 26432","doi":"10.1038/s41598-025-08612-z","pmid":"40691451","tags":["cgrp","neuropeptides-neuroscience","skin-dermatology"],"studyType":"animal-study","evidenceStrength":"low","keyFinding":"Approximately half of itch-responsive PBN-CeA projecting neurons are CGRP+, and optogenetic stimulation of these neurons elicits scratching behavior without enhancing anxiety in mice.","whyItMatters":"Chronic itch is a debilitating symptom affecting millions. Understanding the exact brain circuits involved could lead to targeted therapies, and the CGRP connection is particularly interesting given that anti-CGRP drugs are already available for migraine.","specificNumbers":"Approximately half of serotonin-responsive PBN-CeA neurons are CGRP+. Optogenetic stimulation elicited scratching. Inhibition in chronic itch model significantly reduced spontaneous scratching. No effect on anxiety-like behaviors.","methodology":"Mouse study using Targeted Recombination in Active Populations (TRAP) for labeling, retrograde tracing, and optogenetic stimulation to characterize CGRP+ PBN-CeA itch circuits.","limitations":"Mouse study — itch circuits in human brains may differ. Optogenetic activation is artificial and may not fully replicate natural itch processing. The study examined acute responses, not chronic itch."},{"rthcId":"RPEP-12993","title":"A Case of Intussusception With Bowel Obstruction in a Gastric Roux-en-Y Patient Prescribed Semaglutide.","authors":"Pavuluri, Suresh K; Toumar, Ahmad; Duffy, Andrew J","year":2025,"journal":"Journal of the American College of Emergency Physicians open, 6(2), 100045","doi":"10.1016/j.acepjo.2025.100045","pmid":"39959551","tags":["semaglutide","glp1-receptor-agonists","gastrointestinal-health"],"studyType":"case-report","evidenceStrength":"very-low","keyFinding":"Semaglutide use in a post-Roux-en-Y gastric bypass patient led to intussusception with small bowel obstruction and chemical pancreatitis requiring surgical intervention.","whyItMatters":"Many patients who have had bariatric surgery are now being prescribed GLP-1 drugs for additional weight management or diabetes control. This case highlights that altered gut anatomy may increase the risk of serious GI complications with these medications.","specificNumbers":"Patient: 59-year-old woman with prior Roux-en-Y. Developed long-segment small bowel intussusception, SBO, and chemical pancreatitis. Required laparoscopic surgery converted to laparotomy.","methodology":"Single case report documenting clinical presentation, imaging findings, surgical intervention, and outcome.","limitations":"Single case report — cannot establish causation or incidence rate. The intussusception may have occurred independently of semaglutide use."},{"rthcId":"RPEP-12994","title":"Fructose-induced synaptic and neuronal adaptations at neuropeptide Y/agouti-related peptide neurons.","authors":"Payant, Mikayla A; Sankhe, Aditi S; Miller, Persephone A; Vieira, Sarah S; Dumiaty, Yasmina; Phy-Lim, Jenny; Levy, Zachary L; Chee, Melissa J","year":2025,"journal":"Molecular metabolism, 99, 102209","doi":"10.1016/j.molmet.2025.102209","pmid":"40653085","tags":["neuropeptides-neuroscience","obesity-weight-management","diabetes-glucose-metabolism"],"studyType":"animal-study","evidenceStrength":"low","keyFinding":"High-fructose diets induced synaptic and neuronal adaptations at hypothalamic NPY/AgRP neurons, promoting hyperphagia and fat gain with sex-dependent metabolic effects.","whyItMatters":"Understanding how fructose reprograms brain hunger circuits explains why high-fructose diets drive overeating despite the body increasing fat burning and energy expenditure — the brain overrides metabolic compensation.","specificNumbers":"Male and female mice on 60% high-fructose or 60% high-dextrose diets. Both gained body fat despite increased energy expenditure. Males developed glucose intolerance. Fructose uniquely increased synaptic excitation at NPY/AgRP neurons.","methodology":"Preclinical study feeding male and female mice standard chow, 60% high-fructose, or 60% high-dextrose diets, then analyzing brain neuronal changes, metabolic parameters, and body composition.","limitations":"Mouse study with extreme dietary fructose levels (60%). Human diets typically contain lower fructose percentages. Sex-specific findings need human validation."},{"rthcId":"RPEP-12995","title":"Receptor activity-modifying protein 3 enhances GLP-1-mediated insulin secretion.","authors":"Pearce, Abigail; Kumari, Poonam; Sisk, Claudia M; Harris, Matthew; Yeung, Ho Yan; Winfield, Sabrina; Caron, Kathleen M; Ladds, Graham","year":2025,"journal":"The Journal of biological chemistry, 301(10), 110604","doi":"10.1016/j.jbc.2025.110604","pmid":"40835007","tags":["glp1-receptor-agonists","diabetes-glucose-metabolism","receptor-pharmacology"],"studyType":"in-vitro","evidenceStrength":"low","keyFinding":"RAMP3 interacts with the GLP-1 receptor, biasing signaling toward Ca2+ mobilization (away from cAMP), which enhanced glucose-stimulated insulin secretion in pancreatic cells.","whyItMatters":"Current GLP-1 drugs activate the receptor the same way everywhere in the body, causing side effects. RAMP3 shows a way to achieve tissue-selective signaling that could lead to better-tolerated medications.","specificNumbers":"RAMP3 reduced Gαs coupling, increased Gαq and Gαi coupling. Shifted signaling from cAMP to Ca2+ mobilization. Enhanced glucose-stimulated insulin secretion in RAMP3-overexpressing cells.","methodology":"Cell-based laboratory study examining RAMP3-GLP-1 receptor interaction, signaling bias, surface expression, and functional effects on insulin secretion.","limitations":"Cell-based study — the RAMP3 effects on GLP-1 signaling have not been confirmed in animal models or humans. The therapeutic potential is theoretical at this stage."},{"rthcId":"RPEP-12996","title":"Receptor Activity-Modifying Protein 3 enhances GLP-1-mediated Insulin Secretion.","authors":"Pearce, Abigail; Kumari, Poonam; Sisk, Claudia M; Harris, Matthew; Yeung, Ho Yan; Winfield, Sabrina; Caron, Kathleen M; Ladds, Graham","year":2025,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2025.01.24.634724","pmid":"40832355","tags":["glp1-receptor-agonists","diabetes-glucose-metabolism","receptor-pharmacology"],"studyType":"in-vitro","evidenceStrength":"very-low","keyFinding":"RAMP3 interacts with the GLP-1 receptor, modifying its signaling profile and enhancing insulin secretion — findings later confirmed in the peer-reviewed publication.","whyItMatters":"Demonstrates that receptor accessory proteins can modify GLP-1 signaling in ways that could lead to safer, more targeted diabetes drugs.","specificNumbers":"Same as RPEP-12215.","methodology":"Cell-based laboratory study examining RAMP3-GLP-1 receptor interaction, signaling bias, and functional effects on insulin secretion (preprint version).","limitations":"Preprint version — not yet peer-reviewed at time of posting. The peer-reviewed version was subsequently published in JBC (PMID 40835007)."},{"rthcId":"RPEP-12997","title":"Angiotensin-Converting Enzyme (ACE)-Inhibitor Activity of Novel Peptides Derived from Porcine Liver and Placenta.","authors":"Pearman, Nicholas A; Morris, Gordon A; Smith, Alan M","year":2025,"journal":"Molecules (Basel, Switzerland), 30(3)","doi":"10.3390/molecules30030754","pmid":"39942857","tags":["cardiovascular-health","peptide-synthesis-chemistry"],"studyType":"in-vitro","evidenceStrength":"very-low","keyFinding":"Four peptides from porcine liver and placenta (FWG, MFLG, SDPPLVFVG, FFNDA) demonstrated ACE-inhibitory activity, with placenta hydrolysate outperforming both liver hydrolysate and individual synthetic peptides.","whyItMatters":"Finding natural ACE-inhibiting peptides from food-grade animal byproducts could lead to functional foods or nutraceuticals for blood pressure management, potentially with fewer side effects than pharmaceutical ACE inhibitors.","specificNumbers":"Four peptides identified: FWG, MFLG, SDPPLVFVG, FFNDA. FWG and MFLG more potent than SDPPLVFVG and FFNDA. IC50 values comparable to porcine muscle-derived peptides. Less potent than captopril.","methodology":"In vitro study using papain digestion of porcine tissues, in silico enzymatic cleavage prediction, HPLC-MS/MS identification, peptide synthesis, and ACE inhibition assays.","limitations":"In vitro ACE inhibition only — bioavailability, stability in the digestive system, and actual blood pressure effects in living organisms have not been tested."},{"rthcId":"RPEP-12998","title":"Predictors of Initial and Sustained Glycemic and Weight Response to Tirzepatide: A Post Hoc Analysis of SURPASS-4.","authors":"Pearson, Ewan R; Del Prato, Stefano; Pavo, Imre; Franco, Denise R; Zheng, Junyuan; Nicolay, Claudia; Hemmingway, Andrea; Wiese, Russell J; Kahn, Steven E","year":2025,"journal":"Diabetes, 74(10), 1850-1862","doi":"10.2337/db25-0276","pmid":"40633089","tags":["tirzepatide","glp1-receptor-agonists","diabetes-glucose-metabolism","obesity-weight-management"],"studyType":"secondary-analysis","evidenceStrength":"strong","keyFinding":"75-84% of tirzepatide responders sustained HbA1c ≤6.5% through median 81 weeks; predictors included higher dose, shorter diabetes duration, better baseline beta-cell function, and greater weight loss.","whyItMatters":"Knowing which patients will respond best to tirzepatide helps clinicians personalize treatment decisions, start the right patients earlier, and set realistic expectations about long-term outcomes.","specificNumbers":"75-84% sustained HbA1c <= 6.5% from week 52 to study end (median 81 weeks). 79-82% maintained >= 10% weight loss. Predictors: higher dose, shorter diabetes duration, lower baseline HbA1c, higher HOMA-B, metformin alone, no albuminuria, female sex.","methodology":"Post hoc analysis of the SURPASS-4 randomized trial in people with type 2 diabetes and increased cardiovascular risk, evaluating predictors of initial and sustained glycemic and weight response to tirzepatide.","limitations":"Post hoc analysis — findings are hypothesis-generating, not confirmatory. Results are from a specific trial population with cardiovascular risk and may not generalize to all T2D patients."},{"rthcId":"RPEP-12999","title":"Affordable access to GLP-1 obesity medications: strategies to guide market action and policy solutions in the US.","authors":"Pearson, Steven D; Whaley, Christopher M; Emond, Sarah K","year":2025,"journal":"Journal of comparative effectiveness research, 14(9), e250083","doi":"10.57264/cer-2025-0083","pmid":"40641455","tags":["glp1-receptor-agonists","obesity-weight-management"],"studyType":"policy-analysis","evidenceStrength":"moderate","keyFinding":"While GLP-1 obesity medications are lifetime cost-effective, treating the 100+ million eligible US adults requires new market approaches and policy reforms to achieve affordable access.","whyItMatters":"The most effective obesity treatments in history are available but unaffordable for most people who need them. Without systemic solutions, these drugs will worsen health inequities rather than reduce them.","specificNumbers":"Over 40% of US adults have obesity (100+ million potential users). GLP-1 drugs estimated cost-effective over lifetime. Analyzes emerging market approaches and policy reforms.","methodology":"Policy analysis examining emerging market approaches and policy reforms for achieving affordable access to GLP-1 obesity medications in the US health system.","limitations":"Policy analysis — proposed solutions are theoretical and face political, economic, and regulatory barriers to implementation."},{"rthcId":"RPEP-13000","title":"Marsupial cathelicidins: characterization, antimicrobial activity and evolution in this unique mammalian lineage.","authors":"Peel, Emma; Gonsalvez, Adele; Hogg, Carolyn J; Belov, Katherine","year":2025,"journal":"Frontiers in immunology, 16, 1524092","doi":"10.3389/fimmu.2025.1524092","pmid":"40255401","tags":["antimicrobial-peptides","inflammation-immunity"],"studyType":"in-vitro","evidenceStrength":"low","keyFinding":"Marsupials have undergone lineage-specific cathelicidin gene expansions resulting in a large and diverse antimicrobial peptide repertoire distinct from placental mammals.","whyItMatters":"Antibiotic resistance demands new antimicrobial sources. Marsupials evolved their own diverse antimicrobial peptide toolkit over millions of years — peptides that could inspire entirely new classes of anti-infective drugs.","specificNumbers":"130 cathelicidin genes across 14 marsupial species (10 families). Gene clusters: eutherians 1, marsupials 2, monotremes 3. 32 extant and ancestral peptides tested for antimicrobial activity.","methodology":"Genomic analysis across the marsupial family tree combined with ancestral sequence reconstruction to predict ancestral cathelicidin sequences and characterize antimicrobial activity.","limitations":"Computational and in vitro study. Predicted ancestral peptides are reconstructions, not directly observed. Antimicrobial activity in living marsupials may differ from isolated peptide testing."},{"rthcId":"RPEP-13001","title":"Bovine lactoferricin exerts antibacterial activity against four Gram-negative pathogenic bacteria by transforming its molecular structure.","authors":"Pei, Jie; Xiong, Lin; Wu, Xiaoyun; Chu, Min; Bao, Pengjia; Ge, Qianyun; Guo, Xian","year":2025,"journal":"Frontiers in cellular and infection microbiology, 15, 1508895","doi":"10.3389/fcimb.2025.1508895","pmid":"40453712","tags":["antimicrobial-peptides","peptide-synthesis-chemistry"],"studyType":"in-vitro","evidenceStrength":"very-low","keyFinding":"The intramolecular disulfide bond in bovine lactoferricin transforms its molecular structure, which is essential for its antibacterial activity against four Gram-negative pathogenic bacteria.","whyItMatters":"Understanding how structural changes enable antimicrobial activity helps scientists design more effective peptide antibiotics, potentially overcoming the growing threat of antibiotic-resistant Gram-negative infections.","specificNumbers":"Three variants: native Lfcin, Lfcin with disulfide bond (Lfcin DB), and mutant without disulfide bond (Lfcin C36G). Structural analysis by circular dichroism and AlphaFold3 prediction. Tested against four Gram-negative pathogens.","methodology":"In vitro study synthesizing bovine lactoferricin variants with and without disulfide bonds, testing antibacterial activity against four Gram-negative pathogens, and characterizing structural changes.","limitations":"In vitro study — antibacterial activity in a test tube may not translate to efficacy in living organisms. Bioavailability and stability in the body remain to be tested."},{"rthcId":"RPEP-13002","title":"Trained Immunity in Bladder ILC3s Enhances Mucosal Defense Against Recurrent Urinary Tract Infections.","authors":"Pei, Qiaoqiao; Liu, Jiaqi; Tang, Ziwen; Tan, Jiaqing; Han, Xu; Hu, Xinrong; Liang, Zhou; Li, Feng; Zhu, Changjian; Lin, Ruoni; Zheng, Ruilin; Shen, Jiani; Liu, Qinghua; Mao, Haiping; Wu, Kefei; Chen, Wei; Zhou, Yi","year":2025,"journal":"Biomedicines, 14(1)","doi":"10.3390/biomedicines14010078","pmid":"41595613","tags":["antimicrobial-peptides","inflammation-immunity","infectious-disease"],"studyType":"animal-study","evidenceStrength":"low","keyFinding":"Bladder-resident ILC3s develop trained immunity following uropathogenic E. coli exposure, enhancing their ability to defend against recurrent UTIs.","whyItMatters":"Recurrent UTIs affect millions and are increasingly treated with antibiotics that drive resistance. Harnessing trained immunity in bladder immune cells could provide a new antibiotic-free prevention strategy.","specificNumbers":"ILC3 counts compared between UTI patients and healthy controls. Recurrent UTI mouse model with primary and secondary E. coli inoculation. Adoptive transfer of naive vs UPEC-trained ILC3s.","methodology":"Preclinical study investigating ILC3 trained immunity induction and functional significance in mucosal defense against uropathogenic E. coli in a bladder model.","limitations":"Preclinical study — trained immunity in bladder ILC3s has not been demonstrated in humans. The mechanisms may differ between species."},{"rthcId":"RPEP-13003","title":"Adoption of rimegepant in Denmark: a register-based study on uptake, prescribing patterns and initiator characteristics.","authors":"Pellesi, Lanfranco; Do, Thien Phu; Ernst, Martin Thomsen; Hallas, Jesper; Pottegård, Anton","year":2025,"journal":"The journal of headache and pain, 26(1), 83","doi":"10.1186/s10194-025-02028-w","pmid":"40251473","tags":["cgrp","pain-management"],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"Over 140,000 DDD of rimegepant were prescribed in Denmark by December 2024, with analysis of demographic characteristics, adherence patterns, and concomitant migraine therapy use.","whyItMatters":"Understanding real-world adoption patterns helps predict how new migraine therapies will be used in practice and identifies which patient populations are benefiting first.","specificNumbers":"Over 140,000 DDDs dispensed by December 2024. 88% female, median age 45. 79% prior triptan use, 38% prior NSAID use. 69% met medication overuse criteria before initiation. 63% concomitant triptan use. Early discontinuation was common.","methodology":"Register-based study using nationwide Danish healthcare registry data analyzing rimegepant prescriptions from October 2022 to December 2024.","limitations":"Danish healthcare system may not be representative of other countries. Registry data captures prescriptions but not actual patient-reported outcomes or satisfaction."},{"rthcId":"RPEP-13004","title":"Neurotransmitter Imbalance in Cluster Headache: A Systematic Review of Mechanisms and Therapeutic Targets.","authors":"Pellesi, Lanfranco; Mohammad, Anas; Wang, Wei; Martelletti, Paolo","year":2025,"journal":"Pain and therapy, 14(6), 1629-1645","doi":"10.1007/s40122-025-00778-8","pmid":"40971112","tags":["cgrp","neuropeptides-neuroscience","pain-management"],"studyType":"systematic-review","evidenceStrength":"moderate","keyFinding":"Multiple neurotransmitter and neuropeptide changes have been identified in cluster headache, but study results are inconsistent, highlighting gaps in understanding the neurochemical basis of attacks.","whyItMatters":"Cluster headache remains poorly treated despite its severity. Identifying the specific neurochemical imbalances driving attacks could lead to more targeted and effective therapies.","specificNumbers":"38 studies included. Searched PubMed, Embase, Scopus. Assessed neurotransmitters in plasma, saliva, CSF, and platelets. Histamine and sensory neuropeptides (CGRP, substance P) most consistently altered.","methodology":"Systematic review of PubMed, Embase (Ovid), and Scopus for studies reporting quantitative neurotransmitter measurements in cluster headache patients.","limitations":"Inconsistent findings across studies may reflect differences in methodology, sample timing, and patient populations. Small sample sizes in many individual studies."},{"rthcId":"RPEP-13005","title":"Neurotransmitter Imbalance in Tension-Type Headache: A Systematic Review of Mechanisms and Therapeutic Targets.","authors":"Pellesi, Lanfranco; Yangjeh, Aidin; Hajjaj, Ibrahim; Lababidi, Mousbah; Sarwar, Fezan; Wang, Wei; Martelletti, Paolo","year":2025,"journal":"Pain and therapy, 14(4), 1279-1291","doi":"10.1007/s40122-025-00761-3","pmid":"40588693","tags":["neuropeptides-neuroscience","pain-management"],"studyType":"systematic-review","evidenceStrength":"moderate","keyFinding":"Peripheral and central neurotransmitter alterations are present in tension-type headache but evidence remains inconsistent across studies, limiting therapeutic target identification.","whyItMatters":"TTH affects more people than any other headache disorder, yet treatment options are largely limited to generic painkillers. Understanding the specific neurochemical drivers could enable targeted therapies like those developed for migraine.","specificNumbers":"30 studies included from PubMed and Embase. Substance P elevated in salivary and platelet samples. Beta-endorphins often reduced. Mixed findings for CGRP, serotonin, and other mediators.","methodology":"Systematic review of PubMed and Embase for studies reporting neurotransmitter or neuropeptide levels in tension-type headache patients.","limitations":"Inconsistent findings across studies, likely due to methodological differences and small sample sizes. TTH subtypes may have different neurochemical profiles."},{"rthcId":"RPEP-13006","title":"Revisiting substance P in migraine: a methodological approach inspired by anti-CGRP and anti-PACAP success.","authors":"Pellesi, Lanfranco; Edvinsson, Lars","year":2025,"journal":"The journal of headache and pain, 26(1), 22","doi":"10.1186/s10194-025-01959-8","pmid":"39891050","tags":["cgrp","neuropeptides-neuroscience","pain-management"],"studyType":"narrative-review","evidenceStrength":"low","keyFinding":"The failure of NK-1 receptor antagonists does not necessarily mean substance P is irrelevant to migraine; a systematic re-evaluation using validated methodologies (like those used for CGRP) is warranted.","whyItMatters":"If substance P does contribute to migraine, targeting it could provide additional therapeutic options for the many patients who do not fully respond to anti-CGRP drugs.","specificNumbers":"Proposes randomized, double-blind, placebo-controlled crossover provocation studies in healthy volunteers and migraine patients, modeled on successful CGRP and PACAP provocation studies.","methodology":"Methodological proposal for re-evaluating substance P in migraine using randomized, double-blind provocation studies inspired by the anti-CGRP development framework.","limitations":"This is a proposal, not new experimental data. Previous NK-1 antagonist failures suggest substance P may not be a viable target, though the methodology was different."},{"rthcId":"RPEP-13007","title":"Assessment of Cardiorenal Involvement in Systemic Sclerosis Patients.","authors":"Pellicano, Chiara; D'Ippolito, Giancarlo; Villa, Annalisa; Martellucci, Ottavio; Basile, Umberto; Carnazzo, Valeria; Basile, Valerio; Rosato, Edoardo; Marino, Mariapaola; Gigante, Antonietta","year":2025,"journal":"Biomolecules, 15(9)","doi":"10.3390/biom15091297","pmid":"41008604","tags":["natriuretic-peptides","heart-failure","kidney-renal-health","cardiovascular-health"],"studyType":"narrative-review","evidenceStrength":"moderate","keyFinding":"Cardiorenal involvement is a major driver of morbidity and mortality in systemic sclerosis, with CKD commonly present at PAH diagnosis and independently associated with mortality.","whyItMatters":"SSc patients often have overlapping organ damage that is difficult to untangle. Recognizing the cardiorenal connection and using appropriate biomarkers can improve risk stratification and treatment timing.","specificNumbers":"Reviews troponin, BNP, NT-proBNP, creatinine, cystatin C, NGAL, and galectin-3 as cardiorenal biomarkers in SSc. Type 2 cardiorenal syndrome (CKD from chronic HF) discussed.","methodology":"Review article examining cardiac and renal complications in systemic sclerosis, focusing on biomarker assessment including natriuretic peptides.","limitations":"Review article — does not present new clinical data. SSc is heterogeneous, and cardiorenal involvement varies significantly between patients."},{"rthcId":"RPEP-13008","title":"Screening of homing and tissue-penetrating peptides by microdialysis and in vivo phage display.","authors":"Pemmari, Toini; Prince, Stuart; Wiss, Niklas; Kõiv, Kuldar; May, Ulrike; Mölder, Tarmo; Sudakov, Aleksander; Munoz Caro, Fernanda; Lehtonen, Soili; Uusitalo-Järvinen, Hannele; Teesalu, Tambet; Järvinen, Tero Ah","year":2025,"journal":"Life science alliance, 8(5)","doi":"10.26508/lsa.202201490","pmid":"39933917","tags":["drug-delivery-systems","tissue-engineering-regeneration"],"studyType":"animal-study","evidenceStrength":"low","keyFinding":"Combining in vivo phage display with microdialysis-based parenchymal recovery enables selection of peptides capable of both vascular homing and tissue penetration.","whyItMatters":"Many drug delivery peptides can find the right organ but cannot get drugs deep enough into tissue. This method solves that problem by selecting for both properties simultaneously.","specificNumbers":"Demonstrated in skin wounds (vascularized and diabetic) and retinopathy models. Combined phage display with microdialysis-based parenchymal recovery and high-throughput sequencing.","methodology":"Novel screening approach combining in vivo phage display with microdialysis and high-throughput sequencing to identify peptides with dual homing and tissue-penetrating capabilities.","limitations":"Proof-of-concept methodology. The selected peptides need to be validated individually for therapeutic applications. Microdialysis recovery rates may introduce selection bias."},{"rthcId":"RPEP-13009","title":"Role of neurogenic inflammation in intervertebral disc degeneration.","authors":"Peng, Bao-Gan; Li, Yong-Chao; Yang, Liang","year":2025,"journal":"World journal of orthopedics, 16(1), 102120","doi":"10.5312/wjo.v16.i1.102120","pmid":"39850033","tags":["cgrp","neuropeptides-neuroscience","pain-management","bone-joint-health"],"studyType":"narrative-review","evidenceStrength":"moderate","keyFinding":"Neurogenic inflammation driven by substance P and CGRP from ingrowing nociceptive nerve fibers plays a crucial role in intervertebral disc degeneration, with non-neuronal cells also contributing.","whyItMatters":"Back pain from disc degeneration is one of the leading causes of disability worldwide. Understanding the neurogenic inflammation cycle could lead to targeted treatments that break the cycle and slow disc breakdown.","specificNumbers":"Reviews substance P and CGRP release from nociceptive nerve fibers. Non-neuronal cells (disc cells, immune cells) express functional neuropeptide receptors. TRP channels contribute to neurogenic inflammation.","methodology":"Review article synthesizing evidence on neurogenic inflammation mechanisms in intervertebral disc degeneration.","limitations":"Review of existing literature — no new experimental data. The relative contribution of neurogenic versus other forms of inflammation in disc degeneration is still debated."},{"rthcId":"RPEP-13010","title":"IDO-Dependent Tryptophan Metabolites and Endocan as Effective Diagnostic Biomarkers for Pregnancy with Pulmonary Hypertension.","authors":"Peng, Guixin; Liu, Zhuanghua; Wang, Wenli","year":2025,"journal":"International journal of women's health, 17, 2205-2216","doi":"10.2147/IJWH.S527345","pmid":"40708843","tags":["natriuretic-peptides","cardiovascular-health","reproductive-health"],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"IDO1-dependent tryptophan metabolites and endocan showed potential as effective diagnostic biomarkers for pregnancy-associated pulmonary hypertension.","whyItMatters":"Pulmonary hypertension in pregnancy is often detected late with devastating consequences. Better biomarkers could enable earlier diagnosis and timely intervention.","specificNumbers":"62 patients with pregnancy-related pulmonary hypertension, 86 healthy controls. Measured endocan, BNP, and NT-proBNP by ELISA. IDO-dependent tryptophan metabolites by LC-MS/MS. Endocan correlated with BNP and NT-proBNP.","methodology":"Case-control study of 62 patients with pregnancy-associated pulmonary hypertension versus healthy pregnant controls, measuring serum IDO-dependent tryptophan metabolites and endocan levels.","limitations":"Relatively small sample (n=62). Cross-sectional design cannot determine if biomarker changes precede or follow disease onset. Validation in larger cohorts needed."},{"rthcId":"RPEP-13011","title":"Soybean bioactive peptide supplementation improves gut health and metabolism in broiler chickens.","authors":"Peng, Han; Song, Xiaoyan; Chen, Jialei; Xiong, Xia; Yang, Li; Yu, Chunlin; Qiu, Mohan; Zhang, Zengrong; Hu, Chenming; Zhu, Shiliang; Xia, Bo; Wang, Jiangxian; Xiong, Zhuxiang; Du, Longhuan; Yang, Chaowu","year":2025,"journal":"Poultry science, 104(2), 104727","doi":"10.1016/j.psj.2024.104727","pmid":"39729732","tags":["gastrointestinal-health","inflammation-immunity"],"studyType":"animal-study","evidenceStrength":"low","keyFinding":"Supplementing 0.2% soybean bioactive peptide in broiler feed improved intestinal health and metabolic function, revealed through multi-omics analysis of gut microbiome and metabolome.","whyItMatters":"Finding natural feed supplements that improve poultry health reduces the need for antibiotics in animal agriculture, addressing a major driver of antimicrobial resistance.","specificNumbers":"320 broilers, 2 groups, 10 replicates of 16 birds. 0.2% SBP replaced soybean meal. 70-day experiment. Higher final weight and daily gain (P < 0.05). Lower feed conversion ratio (P < 0.05). Reduced IL-1β and IFN-γ. Increased ZO-1.","methodology":"Randomized controlled study of 320 yellow-feathered broilers (2 groups, 10 replicates, 16 birds each) comparing basal diet versus 0.2% SBP supplementation with multi-omics gut analysis.","limitations":"Single poultry breed (yellow-feathered broilers). Results may not generalize to other breeds or species. Cost-effectiveness of SBP supplementation not assessed."},{"rthcId":"RPEP-13012","title":"Sequence Permutation Generated Lysine and Tryptophan-Rich Antimicrobial Peptides with Enhanced Therapeutic Index.","authors":"Peng, Kuang-Li; Wu, Yu-Hsuan; Hsu, Hsuan-Che; Cheng, Jya-Wei","year":2025,"journal":"Antibiotics (Basel, Switzerland), 14(11)","doi":"10.3390/antibiotics14111077","pmid":"41301573","tags":["antimicrobial-peptides","peptide-synthesis-chemistry"],"studyType":"in-vitro","evidenceStrength":"very-low","keyFinding":"Sequence permutation of lysine/tryptophan-rich AMPs generated variants with enhanced therapeutic index, addressing key limitations of clinical antimicrobial peptide application.","whyItMatters":"Antibiotic resistance is a global crisis. Improving the safety and efficacy of antimicrobial peptides through AI-guided design could accelerate their path from lab to clinic as antibiotic alternatives.","specificNumbers":"Clockwise sequence permutation of W5K/A9W. Derivative peptides had identical molecular weight, net charge, and amino acid composition. Some showed enhanced therapeutic index (better antimicrobial activity relative to toxicity).","methodology":"AI-assisted peptide design using sequence permutation, followed by synthesis and testing of antimicrobial activity, salt sensitivity, bioavailability, and cytotoxicity.","limitations":"In vitro study — enhanced therapeutic index in the lab does not guarantee clinical success. In vivo stability and efficacy remain to be tested."},{"rthcId":"RPEP-13013","title":"Leveraging the Therapeutic Potential of Natural Peptide Panurgines: Hydrocarbon Stapling Strategy Enhances Their Efficacy Against Breast Cancer.","authors":"Peng, Zhongzhong; Chen, Lei; Miao, Xianyuan; Wang, Qiongqiong; Fu, Shuyue; Zhang, Xikai; Zhou, Xiao; Ren, Sijia; Lao, Yehua; Li, Yinghua; Wang, Kaifeng; He, Shipeng","year":2025,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 31(10), e70047","doi":"10.1002/psc.70047","pmid":"40887726","tags":["antimicrobial-peptides","cancer-oncology","peptide-synthesis-chemistry"],"studyType":"in-vitro","evidenceStrength":"very-low","keyFinding":"Hydrocarbon stapling of panurgine peptides from bee venom enhanced their stability, cell membrane permeability, and anti-breast cancer efficacy compared to linear counterparts.","whyItMatters":"Natural anticancer peptides from venoms are promising but fragile. Stapling technology makes them viable drug candidates by solving the stability problem that has prevented clinical development.","specificNumbers":"PNG-5 showed improved helicity, membrane permeability, proteolytic stability, and antitumor activity compared to unmodified panurgines.","methodology":"Peptide synthesis of stapled panurgine variants using hydrocarbon stapling modifications, followed by testing of stability, cell penetration, and anti-breast cancer activity.","limitations":"In vitro study — anti-breast cancer activity was tested in cell cultures, not in animal models or humans. The stapled peptides'effect on healthy cells and in vivo toxicity remain to be assessed."},{"rthcId":"RPEP-13014","title":"Temporal and subgroup disparities in mediation effects on cardiovascular outcomes with liraglutide and semaglutide: a post-hoc analysis of LEADER and SUSTAIN-6 trials.","authors":"Peng, Zi-Yang; Lee, Yu-Hsuan; Ou, Huang-Tz; Kuo, Shihchen","year":2025,"journal":"Cardiovascular diabetology, 24(1), 465","doi":"10.1186/s12933-025-03007-w","pmid":"41286734","tags":["semaglutide","glp1-receptor-agonists","cardiovascular-health","diabetes-glucose-metabolism","kidney-renal-health"],"studyType":"secondary-analysis","evidenceStrength":"strong","keyFinding":"HbA1c, UACR, and systolic blood pressure only partially mediate GLP-1 RA cardiovascular benefits, with time-varying effects that differ between liraglutide and semaglutide and across patient subgroups.","whyItMatters":"Understanding why GLP-1 drugs protect the heart helps identify who benefits most and may reveal new cardiovascular protection mechanisms that could be targeted by future drugs.","specificNumbers":"LEADER: 9,340 subjects. SUSTAIN-6: 3,297 subjects. Ages ~64. Causal mediation analysis for HbA1c, UACR, and SBP effects on 3P-MACE over time.","methodology":"Post hoc causal mediation analysis of the LEADER (liraglutide) and SUSTAIN-6 (semaglutide) randomized controlled trials, assessing time-varying mediation of 3P-MACE outcomes.","limitations":"Post hoc analysis — findings are hypothesis-generating. Mediation analysis has inherent assumptions about causal pathways that may not hold. Unmeasured confounders may exist."},{"rthcId":"RPEP-13015","title":"Challenges in Modelling the Cost Effectiveness of Pharmacotherapies for Obesity.","authors":"Pennington, Becky; Cummins, Ewen; Chandler, Albany; Fotheringham, James","year":2025,"journal":"PharmacoEconomics, 43(10), 1171-1178","doi":"10.1007/s40273-025-01520-0","pmid":"40717166","tags":["glp1-receptor-agonists","obesity-weight-management"],"studyType":"narrative-review","evidenceStrength":"moderate","keyFinding":"Cost-effectiveness modeling for obesity pharmacotherapies faces unique challenges from interacting uncertainties: short trial durations, weight regain patterns, and complex relationships between weight loss and long-term cardiometabolic outcomes.","whyItMatters":"These modeling challenges directly affect whether insurance companies and health systems decide to cover obesity drugs — potentially determining access for millions of patients.","specificNumbers":"Discusses four modeling challenges for semaglutide, tirzepatide, liraglutide, and newer agents. Considers lifetime treatment horizon and substantial eligible populations.","methodology":"Methodological commentary analyzing challenges in health technology assessment modeling for obesity drugs, including extrapolation issues and uncertainty interactions.","limitations":"Commentary on methodology — does not provide new cost-effectiveness data. The challenges outlined do not have easy solutions."},{"rthcId":"RPEP-13016","title":"Development of Silk Fibroin-Based Sponges Loaded with LL-37-Derived Peptides for the Control of Orthopedic Infections.","authors":"Pennone, Vincenzo; Meogrossi, Giada; Carenzi, Giacomo; Sarlah, David; Biagiotti, Marco; Lovati, Arianna B","year":2025,"journal":"International journal of molecular sciences, 26(16)","doi":"10.3390/ijms26167775","pmid":"40869096","tags":["antimicrobial-peptides","drug-delivery-systems","bone-joint-health","infectious-disease"],"studyType":"in-vitro","evidenceStrength":"very-low","keyFinding":"Silk fibroin sponges successfully loaded with FK-16 and GF-17 antimicrobial peptides showed sustained release properties suitable for local control of orthopedic implant infections.","whyItMatters":"Implant infections often require implant removal and prolonged antibiotic treatment. A local antimicrobial sponge could prevent infections at the surgical site while promoting bone healing.","specificNumbers":"FK-16: >90% release within 24 h, then stable plateau. Bactericidal against MRSE clinical strains. GF-17: lower release efficiency, weaker antimicrobial effect. Neither effective against MRSA in this system.","methodology":"Materials science study developing and characterizing silk fibroin (SF) and osteoinductive peptide-enriched SF (PSF) sponges for local FK-16 and GF-17 delivery, assessing swelling, release kinetics, and antimicrobial properties.","limitations":"In vitro study — release kinetics and antimicrobial efficacy in surgical settings remain to be tested. Biocompatibility in living tissue needs validation."},{"rthcId":"RPEP-13017","title":"Sex-dependent effects of ethanol withdrawal from a single- and repeated binge episode exposures on social anxiety-like behavior and neuropeptide gene expression in adolescent rats.","authors":"Penta, Peter T; Villarreal, Susanna; Rameas, Caitlin I; Collins, Ella C; Towner, Trevor T; Varlinskaya, Elena I; Werner, David F","year":2025,"journal":"Alcohol (Fayetteville, N.Y.), 122, 71-80","doi":"10.1016/j.alcohol.2024.10.001","pmid":"39442640","tags":["oxytocin","neuropeptides-neuroscience","mental-health-psychiatry","addiction-substance-use"],"studyType":"animal-study","evidenceStrength":"low","keyFinding":"Single and repeated binge ethanol withdrawal in adolescent rats produced sex-dependent effects on social anxiety-like behavior and neuropeptide gene expression.","whyItMatters":"Understanding sex differences in how adolescent binge drinking affects the brain could help develop sex-specific prevention and treatment strategies for alcohol use disorder.","specificNumbers":"Assessed social investigation behavior during acute withdrawal from single and repeated binge episodes. Measured OXT and AVP gene expression in hypothalamus and central amygdala. Sex-dependent effects observed.","methodology":"Preclinical study exposing adolescent male and female rats to single or repeated binge ethanol episodes, then measuring social anxiety-like behavior and neuropeptide gene expression during acute withdrawal and protracted abstinence.","limitations":"Animal study — findings may not directly translate to human adolescents. Ethanol dosing patterns in rats approximate but do not perfectly replicate human binge drinking."},{"rthcId":"RPEP-13018","title":"Guanidinium-Stapled Helical Peptides for Targeting Protein-Protein Interactions.","authors":"Perdriau, Camille; Luton, Anaïs; Zimmeter, Katharina; Neuville, Maxime; Saragaglia, Claire; Peluso-Iltis, Carole; Osz, Judit; Kauffmann, Brice; Collie, Gavin W; Rochel, Natacha; Guichard, Gilles; Pasco, Morgane","year":2025,"journal":"Angewandte Chemie (International ed. in English), 64(5), e202416348","doi":"10.1002/anie.202416348","pmid":"39714600","tags":["peptide-synthesis-chemistry","drug-delivery-systems"],"studyType":"in-vitro","evidenceStrength":"very-low","keyFinding":"Guanidinium-stapling provides a modular, solid-phase-compatible method for constraining helical peptides, with the guanidinium group potentially enhancing target binding at protein-protein interfaces.","whyItMatters":"Protein-protein interactions drive many diseases but are among the hardest drug targets. This new stapling chemistry adds a tool to the drug discovery toolkit with built-in target-binding features.","specificNumbers":"Achieved on solid support using orthogonally protected lysine residues. Evaluated multiple stapled peptides against different protein targets. X-ray structures of four complexes solved. Guanidinium exhibited distinct cis/trans conformation.","methodology":"Peptide chemistry study developing guanidinium stapling using orthogonally protected lysine residues on solid support, with characterization of staple size, helicity, and modularity.","limitations":"Proof-of-concept chemistry study. Biological activity of guanidinium-stapled peptides against specific disease targets remains to be demonstrated."},{"rthcId":"RPEP-13019","title":"Proteomic and peptidomic characterization of Rhaebo guttatus (Anura: Bufonidae) skin secretion.","authors":"Pereira Dos Santos, Natalia Gabrielly; Mendes, Laís Campelo; Juliano, Maria Aparecida; Caldeira, Cleópatra Alves da Silva; Beraldo-Neto, Emídio; Pimenta, Daniel Carvalho","year":2025,"journal":"Toxicon : official journal of the International Society on Toxinology, 259, 108359","doi":"10.1016/j.toxicon.2025.108359","pmid":"40222709","tags":["antimicrobial-peptides","peptide-synthesis-chemistry"],"studyType":"in-vitro","evidenceStrength":"very-low","keyFinding":"First proteomic and peptidomic characterization of R. guttatus skin secretion identified proteins and peptides with similarities to known toad venoms and potential biological activities.","whyItMatters":"Amphibian skin secretions are a rich source of bioactive molecules for drug discovery. Characterizing previously unstudied species expands the chemical library available for pharmaceutical development.","specificNumbers":"Used nanoLC-ESI-q-ToF for shotgun proteomics and peptidomics. Identified proteins associated with muscle contraction, oxidative stress, and immunity (galectin, annexin).","methodology":"Shotgun proteomics and peptidomics analysis using nano liquid chromatography coupled to high-resolution mass spectrometry (nanoLC-ESI-q-ToF).","limitations":"Descriptive study — identified proteins and peptides have not been tested for specific biological activities. Peptide functions are predicted based on homology, not experimental validation."},{"rthcId":"RPEP-13020","title":"Perioperative glucagon-like Peptide-1 receptor agonist use and clinical outcomes following lower extremity fracture fixation: A large retrospective cohort study with two year follow up.","authors":"Pereira, Daniel E; Tummala, Sri; Mittal, Mehul M; Obey, Mitchel; Berkes, Marschall B; McAndrew, Christopher M; Wilson, Jenna L","year":2025,"journal":"Injury, 56(11), 112746","doi":"10.1016/j.injury.2025.112746","pmid":"40915058","tags":["glp1-receptor-agonists","bone-joint-health"],"studyType":"retrospective-cohort","evidenceStrength":"moderate","keyFinding":"Large propensity-matched retrospective analysis compared perioperative GLP-1 RA users with non-users following lower extremity fracture fixation with two-year follow-up.","whyItMatters":"Millions of GLP-1 RA users may need fracture surgery. Knowing whether these drugs impair or help bone healing is critical for surgical planning and medication management decisions.","specificNumbers":"275,970 patients analyzed. 6,125 propensity-matched pairs. Matched on age, sex, tobacco, diabetes, hypertension, hyperlipidemia, heart disease, lung disease, and BMI. Higher nonunion rate in GLP-1 group at 1 year.","methodology":"Retrospective propensity-matched cohort study from a large multicenter database, comparing GLP-1 RA users (within one year of surgery) versus non-users after lower extremity fracture fixation.","limitations":"Retrospective design — cannot prove causation. GLP-1 RA users may differ from non-users in ways not captured by propensity matching. Specific fracture types and healing metrics vary."},{"rthcId":"RPEP-13021","title":"Managing obesity-related male infertility: insights from weight loss intervention.","authors":"Pereira, Thairo A; Thaker, Niral; Rubez, André C; Lima, Victor F N; Bernie, Helen L; Esteves, Sandro C","year":2025,"journal":"Human reproduction (Oxford, England), 40(11), 2027-2037","doi":"10.1093/humrep/deaf180","pmid":"41024420","tags":["glp1-receptor-agonists","obesity-weight-management","reproductive-health","hormones-endocrine"],"studyType":"narrative-review","evidenceStrength":"moderate","keyFinding":"Weight loss interventions including lifestyle modification, bariatric surgery, and GLP-1 receptor agonists can improve obesity-related male reproductive dysfunction through multiple mechanisms.","whyItMatters":"Male infertility is increasingly linked to the obesity epidemic. Understanding how different weight loss approaches affect fertility gives men and their doctors more treatment options.","specificNumbers":"Reviews lifestyle modification, bariatric surgery, and GLP-1 RA effects on testosterone, semen quality, and reproductive outcomes. Bariatric surgery raises testosterone but may lower sperm count in some men.","methodology":"Mini-review summarizing current evidence on the impact of weight loss interventions on male fertility outcomes.","limitations":"Mini-review — does not systematically evaluate all available evidence. Most fertility studies are small and observational. Long-term effects of GLP-1 drugs on male fertility are unknown."},{"rthcId":"RPEP-13022","title":"Glucagon-like peptide-1 receptor agonists and its possible nephroprotective role: a systematic review.","authors":"Perencin, Alessandro; Ceolin, Chiara; Papa, Mario V; DI Marzio, Benedetta; Zanforlini, Bruno M; Devita, Maria; Curreri, Chiara; Gasparini, Giulia; Sergi, Giuseppe; DE Rui, Marina","year":2025,"journal":"Minerva medica, 116(6), 454-460","doi":"10.23736/S0026-4806.25.09709-5","pmid":"40932602","tags":["glp1-receptor-agonists","kidney-renal-health","diabetes-glucose-metabolism"],"studyType":"systematic-review","evidenceStrength":"moderate","keyFinding":"GLP-1 receptor agonists show potential nephroprotective effects in type 2 diabetes, including improvements in eGFR and albuminuria, though dedicated renal outcome studies are limited.","whyItMatters":"Kidney disease is a major complication of diabetes. If GLP-1 drugs protect the kidneys in addition to their metabolic benefits, it strengthens the case for their early and widespread use in diabetic patients.","specificNumbers":"13 studies included (clinical trials and observational). Assessed eGFR and ACR outcomes. Quality assessed with validated bias risk tools. Overall trend toward nephroprotection but inconsistent across studies.","methodology":"Systematic review of PubMed, Embase, Web of Science, and Cochrane Library for studies examining GLP-1 RA effects on kidney outcomes in type 2 diabetes patients.","limitations":"Few studies have been specifically designed to assess kidney outcomes as primary endpoints. Most kidney data comes from secondary analyses of cardiovascular or diabetes trials."},{"rthcId":"RPEP-13023","title":"Growth Hormone-Releasing Hormone (GHRH) Antagonist Peptides Combined with PI3K Isoform Inhibitors Enhance Cell Death in Prostate Cancer.","authors":"Perez-Stable, Carlos; de Las Pozas, Alicia; Wangpaichitr, Medhi; Sha, Wei; Wang, Haibo; Cai, Renzhi; Schally, Andrew V","year":2025,"journal":"Cancers, 17(10)","doi":"10.3390/cancers17101643","pmid":"40427140","tags":["growth-hormone-peptides","cancer-oncology"],"studyType":"in-vitro","evidenceStrength":"low","keyFinding":"PI3Kα and PI3Kβ inhibitors consistently increased cell death when combined with GHRH antagonist peptides MIA-602/690 across all prostate cancer types including androgen-resistant disease.","whyItMatters":"Advanced prostate cancer resistant to hormone therapy has limited treatment options. This peptide-drug combination could provide a new therapeutic strategy for these difficult-to-treat cancers.","specificNumbers":"MIA-602/690 decreased androgen receptors and likely enhanced PI3K (negative feedback). Adding PI3K alpha or beta inhibitors countered this. Affected apoptosis (Mcl-1L to Mcl-1S switch), proliferation (E2F1, cyclin A), AKT, and ERK.","methodology":"In vitro drug combination screening testing GHRH antagonists (MIA-602, MIA-690) with PI3K isoform inhibitors against multiple prostate cancer cell lines.","limitations":"In vitro cell line study — drug combinations effective in culture may not translate to clinical efficacy. Dosing, timing, and toxicity in living organisms need to be assessed."},{"rthcId":"RPEP-13024","title":"Designing GLP-1 delivery: structural perspectives and formulation approaches for optimized therapy.","authors":"Peri, Ravi Vamsi; Anchan, Harsh; Jonnalagadda, Kamal; Varghese, Ryan; Gupta, Pardeep","year":2025,"journal":"Nutrition & diabetes, 15(1), 53","doi":"10.1038/s41387-025-00397-4","pmid":"41276534","tags":["glp1-receptor-agonists","drug-delivery-systems","peptide-synthesis-chemistry"],"studyType":"narrative-review","evidenceStrength":"moderate","keyFinding":"Various structural modifications and delivery strategies have successfully overcome GLP-1's fragility, enabling the development of long-acting and orally available GLP-1 therapeutics.","whyItMatters":"Understanding how GLP-1 drugs were engineered explains why different formulations exist and informs the development of next-generation versions with even better convenience and efficacy.","specificNumbers":"Reviews N-terminal, C-terminal, fatty acid side chain, and large molecule conjugation modifications. Discusses half-life extension, receptor binding, and bioactivity improvements.","methodology":"Comprehensive review of GLP-1 structural biology, DPP-IV resistance strategies, pharmacokinetic modifications, and advanced drug delivery formulation approaches.","limitations":"Review article — does not provide new experimental data. Some discussed delivery approaches are still experimental."},{"rthcId":"RPEP-13025","title":"GLP-1 Receptor Agonists and Clinical Outcomes after Endovascular Treatment of Unruptured Aneurysms in Type 2 Diabetes.","authors":"Perng, Pang-Shuo; Chang, Yu; Chuang, Ming-Tsung; Wong, Chia-En; Sun, Yuan-Ting; Wang, Hao-Kuang; Chi, Kuan-Yu; Lee, Jung-Shun; Wang, Liang-Chao; Huang, Chih-Yuan","year":2025,"journal":"Stroke (Hoboken, N.J.), 5(6), e001933","doi":"10.1161/SVIN.125.001933","pmid":"41608727","tags":["glp1-receptor-agonists","neuropeptides-neuroscience","cardiovascular-health"],"studyType":"retrospective-cohort","evidenceStrength":"moderate","keyFinding":"GLP-1 receptor agonist use was associated with improved clinical outcomes following endovascular treatment of unruptured intracranial aneurysms in type 2 diabetes patients.","whyItMatters":"Brain aneurysm treatment carries risks of complications. If GLP-1 drugs provide neuroprotection during and after these procedures, they could improve outcomes for the millions of diabetic patients with aneurysms.","specificNumbers":"6,824 patients met criteria. 447 per group after propensity matching. No short/mid-term mortality differences. Long-term mortality significantly lower in GLP-1RA users.","methodology":"Retrospective cohort study using the TriNetX multicenter database, comparing outcomes in T2D patients with unruptured intracranial aneurysms who used GLP-1 RAs versus those who did not.","limitations":"Retrospective observational study — cannot prove causation. GLP-1 RA users may differ from non-users in health-seeking behaviors and overall health status."},{"rthcId":"RPEP-13026","title":"First Autopsy-confirmed Complete Remission of Metastatic Neuroendocrine Neoplasm of Tailgut Cyst After a Single Cycle of Alpha-Peptide Receptor Radionuclide Therapy With [225Ac]Ac-DOTA-LM3.","authors":"Perrone, Elisabetta; Shaheen, Shagufta; Kunz, Pamela L; Henri, Heather C; Baum, Richard P","year":2025,"journal":"Clinical nuclear medicine","doi":"10.1097/RLU.0000000000006201","pmid":"41308086","tags":["peptide-receptor-radionuclide-therapy","neuroendocrine-tumors"],"studyType":"case-report","evidenceStrength":"very-low","keyFinding":"Autopsy confirmed complete pathological remission of widely metastatic neuroendocrine cancer after just one cycle of [225Ac]Ac-DOTA-LM3 alpha-PRRT — a first in the literature.","whyItMatters":"Autopsy-confirmed complete remission is the gold standard for proving a treatment works. This first-ever case demonstrates the extraordinary cancer-killing potential of alpha-particle PRRT.","specificNumbers":"78-year-old man. NEN G2 from tailgut cyst. Prior surgery, lanreotide, and Lu-177 DOTATATE. 1 cycle Ac-225 DOTA-LM3. Complete remission confirmed at autopsy. Death from gastric adenocarcinoma (unrelated).","methodology":"Single case report with autopsy confirmation of treatment response after one cycle of Actinium-225 labeled DOTA-LM3 PRRT.","limitations":"Single case — cannot determine how often complete remission occurs. The patient died from an unrelated complication (bile duct obstruction), so long-term survival benefit could not be assessed."},{"rthcId":"RPEP-13027","title":"Peptide Receptor Radionuclide Therapy (PRRT) Using Actinium-225- and Ac-225/Lutetium-177-Labeled (TANDEM) Somatostatin Receptor Antagonist DOTA-LM3 in Patients with Neuroendocrine Neoplasm: A Retrospective Study Concerning Safety and Survival.","authors":"Perrone, Elisabetta; Calcagni, Maria Lucia; Leccisotti, Lucia; Moretti, Roberto; Ghai, Kriti; Eismant, Aleksandr; Parkar, Tanay; Greifenstein, Lukas; Baum, Richard Paul","year":2025,"journal":"Cancers, 17(18)","doi":"10.3390/cancers17183070","pmid":"41008911","tags":["peptide-receptor-radionuclide-therapy","neuroendocrine-tumors"],"studyType":"retrospective-cohort","evidenceStrength":"moderate","keyFinding":"35 patients received 57 cycles of [225Ac]Ac-DOTA-LM3 (alone or TANDEM with Lu-177) for resistant NEN, showing manageable safety and promising survival outcomes.","whyItMatters":"This is the largest published series on Ac-225 alpha-PRRT for neuroendocrine cancers, providing critical safety and efficacy data for a treatment approach that may become standard care.","specificNumbers":"35 patients, 57 cycles (24 monotherapy, 33 TANDEM). March 2022-September 2024. Pancreas most common primary (n=19). Mostly mild acute adverse events (nausea n=8). Grade 3/4: anemia (n=2), leukocytopenia (n=1).","methodology":"Retrospective study of 35 patients with advanced SSTR-positive NEN treated with Ac-225 DOTA-LM3 PRRT (monotherapy and TANDEM), assessing safety, survival, and follow-up duration.","limitations":"Retrospective design without a control group. Patient heterogeneity in prior treatments and disease characteristics. Small sample for definitive survival analysis."},{"rthcId":"RPEP-13028","title":"TANDEM Peptide Receptor Radionuclide Therapy Using [ 225 Ac]Ac-/[ 177 Lu]Lu-DOTA-LM3 in a Patient With Parotid Gland Metastasis From Pancreatic Neuroendocrine Neoplasm.","authors":"Perrone, Elisabetta; Ghai, Kriti; Eismant, Aleksandr; Baum, Richard P","year":2025,"journal":"Clinical nuclear medicine, 50(10), e605-e607","doi":"10.1097/RLU.0000000000005782","pmid":"40051072","tags":["peptide-receptor-radionuclide-therapy","neuroendocrine-tumors"],"studyType":"case-report","evidenceStrength":"very-low","keyFinding":"TANDEM PRRT with Ac-225/Lu-177 labeled DOTA-LM3 (somatostatin receptor antagonist) achieved partial remission in all metastatic sites of a treatment-refractory pancreatic NEN with parotid metastasis.","whyItMatters":"This demonstrates that when standard PRRT fails, switching to a receptor antagonist-based approach with alpha-emitting radiation can still achieve meaningful tumor control.","specificNumbers":"38-year-old woman. Pancreatic NEN with parotid metastasis. Prior DOTATOC PRRT and surgery failed. 2 cycles TANDEM-PRRT (Ac-225 + Lu-177 DOTA-LM3). Partial remission in parotid and liver.","methodology":"Single case report of a 38-year-old woman with progressive metastatic pancreatic NEN treated with TANDEM PRRT after failure of prior therapies.","limitations":"Single case report — success in one patient does not guarantee broader efficacy. Optimal dosing and long-term outcomes need larger studies."},{"rthcId":"RPEP-13029","title":"A Closer Look at the Dermatological Profile of GLP-1 Agonists.","authors":"Persson, Calista; Eaton, Allison; Mayrovitz, Harvey N","year":2025,"journal":"Diseases (Basel, Switzerland), 13(5)","doi":"10.3390/diseases13050127","pmid":"40422559","tags":["glp1-receptor-agonists","skin-dermatology","inflammation-immunity"],"studyType":"systematic-review","evidenceStrength":"moderate","keyFinding":"GLP-1 RAs exert direct dermatological effects including potential benefits in inflammatory skin diseases, expanding their known therapeutic profile beyond metabolic applications.","whyItMatters":"With millions of people now taking GLP-1 drugs, understanding skin effects helps clinicians and patients anticipate dermatological changes and could open new treatment paths for skin diseases.","specificNumbers":"51 studies met criteria. 34 reported adverse effects (hypersensitivity, injection-site reactions, pruritus, urticaria, angioedema, bullous pemphigoid). 17 reported beneficial outcomes (psoriasis, HS, wound healing).","methodology":"Systematic review of EMBASE, PubMed, Web of Science, and Google Scholar from 2014-2025, including peer-reviewed human studies on GLP-1 RA dermatological effects.","limitations":"Heterogeneous studies with varying designs. Some skin effects may be related to weight loss rather than direct GLP-1 receptor activity in skin."},{"rthcId":"RPEP-13030","title":"Exploring the Innate Immunity in Invertebrates.","authors":"Perveen, Nighat; Kishore, Uday; Al Aiyan, Ahmad; Willingham, Arve Lee; Mohteshamuddin, Khaja","year":2025,"journal":"Advances in experimental medicine and biology, 1476, 411-423","doi":"10.1007/978-3-031-85340-1_16","pmid":"40622552","tags":["antimicrobial-peptides","inflammation-immunity"],"studyType":"narrative-review","evidenceStrength":"moderate","keyFinding":"Invertebrate innate immunity relies on diverse phagocytic cells and antimicrobial peptides that represent ancient, conserved defense mechanisms against pathogens.","whyItMatters":"Invertebrate antimicrobial peptides evolved over hundreds of millions of years of pathogen warfare. Understanding them could reveal new antimicrobial strategies and fundamental principles of immune defense.","specificNumbers":"Reviews TLRs, NLRs, scavenger receptors, phagocytes (amebocytes, hemocytes, coelomocytes), and antimicrobial peptides across invertebrate groups.","methodology":"Review chapter examining innate immune mechanisms across invertebrate phyla, including cellular receptors, phagocytes, and antimicrobial peptide systems.","limitations":"Broad overview chapter — lacks depth on specific species or peptide families. Direct therapeutic applications for human medicine are not addressed."},{"rthcId":"RPEP-13031","title":"Marine Jellyfish Collagen and Other Bioactive Natural Compounds from the Sea, with Significant Potential for Wound Healing and Repair Materials.","authors":"Pesterau, Ana-Maria; Popescu, Antoanela; Sirbu, Rodica; Cadar, Emin; Busuricu, Florica; Dragan, Ana-Maria Laura; Pascale, Carolina; Ionescu, Ana-Maria; Bogdan-Andreescu, Claudia Florina; Radu, Marius-Daniel; Tomescu, Cezar Laurentiu","year":2025,"journal":"Marine drugs, 23(6)","doi":"10.3390/md23060252","pmid":"40559661","tags":["collagen-peptides","antimicrobial-peptides","drug-delivery-systems","skin-dermatology"],"studyType":"in-vitro","evidenceStrength":"very-low","keyFinding":"A composite hydrogel formulated from jellyfish collagen peptides and brown algae extract showed characteristics suitable for wound healing and skin repair applications.","whyItMatters":"Chronic wounds are a growing healthcare burden. Marine-derived biomaterials offer sustainable, biocompatible alternatives to synthetic wound dressings with built-in biological activity.","specificNumbers":"Collagen peptides from Rhizostoma pulmo jellyfish. Hydroethanolic extracts from Cystoseira barbata brown alga. Assessed polysaccharides, proteins, lipids, total phenol content, antioxidant, and antimicrobial activity.","methodology":"Materials development study characterizing a composite hydrogel from Rhizostoma pulmo jellyfish collagen peptides and Cystoseira barbata seaweed extract, both from the Romanian Black Sea coast.","limitations":"Preliminary materials characterization study. Wound healing efficacy has not been tested in animal models or clinical settings."},{"rthcId":"RPEP-13032","title":"Proteomic pathways across the ejection fraction spectrum in patients with heart failure and diabetes mellitus: an EXSCEL trial substudy.","authors":"Peters, Anthony E; Nguyen, Maggie; Green, Jennifer B; Pearson, Ewan R; Buse, John B; Sourij, Harald; Hernandez, Adrian F; Sattar, Naveed; Holman, Rury R; Mentz, Robert J; Shah, Svati H","year":2025,"journal":"Scientific reports, 15(1), 30170","doi":"10.1038/s41598-025-14414-0","pmid":"40825966","tags":["glp1-receptor-agonists","heart-failure","cardiovascular-health"],"studyType":"secondary-analysis","evidenceStrength":"moderate","keyFinding":"Profiling ~5,000 proteins revealed distinct biological pathways across HFpEF, HFmrEF, and HFrEF in diabetic patients, with exenatide modifying some proteomic signatures.","whyItMatters":"Understanding the biological differences between heart failure subtypes could lead to subtype-specific treatments rather than one-size-fits-all approaches.","specificNumbers":"1,199 participants with prevalent HF from EXSCEL trial. ~5,000 proteins profiled via SomaScan. Compared HFpEF (EF>55%), HFmrEF (40-55%), HFrEF (<40%). Baseline and 12-month samples.","methodology":"Proteomic substudy of the EXSCEL randomized trial using SomaLogic SomaScan platform to measure ~5,000 proteins in baseline and 12-month samples from 1,199 participants with T2DM.","limitations":"Substudy of a trial not designed for heart failure as primary endpoint. Proteomic associations are observational and need functional validation."},{"rthcId":"RPEP-13033","title":"Challenging activity and signaling bias in tachykinin NK1 and NK2 receptors by truncated neuropeptides.","authors":"Petersen, Jacob E; Pavlovskyi, Artem; Madsen, Jesper J; Schwartz, Thue W; Frimurer, Thomas M; Olsen, Ole H","year":2025,"journal":"The Journal of biological chemistry, 301(6), 108522","doi":"10.1016/j.jbc.2025.108522","pmid":"40254253","tags":["neuropeptides-neuroscience","receptor-pharmacology","pain-management"],"studyType":"in-vitro","evidenceStrength":"very-low","keyFinding":"Truncated tachykinin analogs retain receptor activity but show altered signaling bias at NK1R and NK2R, with the shortest functional versions being SP(6-11) and NKA(5-10).","whyItMatters":"Understanding how peptide length affects receptor signaling helps design drugs that activate beneficial pathways while avoiding harmful ones — key for developing safer tachykinin-based therapies.","specificNumbers":"12 SP analogs and 10 NKA analogs tested. SP(6-11) and NKA(5-10) shortest versions. Measured cAMP (Gs) and IP3 (Gq) accumulation via BRET assays at NK1R and NK2R.","methodology":"In vitro receptor pharmacology study progressively truncating SP and NKA, testing signaling activity at NK1R and NK2R with free and acetylated N-terminal variants.","limitations":"In vitro study — signaling bias in cell assays may not directly predict in vivo pharmacological effects. Only two receptor subtypes were studied."},{"rthcId":"RPEP-13034","title":"Development of a bioactive hyaluronic acid hydrogel functionalised with antimicrobial peptides for the treatment of chronic wounds.","authors":"Petit, Noémie; Gomes, Ana; Chang, Yu-Yin Joanne; Da Silva, Jessica; Leal, Ermelindo C; Carvalho, Eugénia; Gomes, Paula; Browne, Shane","year":2025,"journal":"Biomaterials science, 13(13), 3561-3575","doi":"10.1039/d5bm00567a","pmid":"40331923","tags":["antimicrobial-peptides","drug-delivery-systems","skin-dermatology"],"studyType":"in-vitro","evidenceStrength":"very-low","keyFinding":"AcHyA hydrogels functionalized with gelatin and antimicrobial peptide PP4-3.1 formed stable in situ gels that enhanced cellular responses while providing antimicrobial activity for chronic wounds.","whyItMatters":"Chronic wound infections are a major healthcare burden. A single material that both promotes healing and prevents infection could simplify wound care and improve outcomes.","specificNumbers":"0.5% gelatin identified as optimal. Rapid gelation, elastic behavior, uniform mesh size. Supported fibroblast and endothelial cell adhesion and spreading. AMP PP4-3.1 provided antimicrobial activity.","methodology":"Biomaterials study developing and characterizing AcHyA-gelatin and AcHyA-AMP hydrogels via thiol-acrylate crosslinking, assessing mechanical properties, cell compatibility, and antimicrobial activity.","limitations":"In vitro characterization study. Wound healing efficacy in animal models or clinical settings has not been tested."},{"rthcId":"RPEP-13035","title":"Effects of Semaglutide Treatment on Psoriatic Lesions in Obese Patients with Type 2 Diabetes Mellitus: An Open-Label, Randomized Clinical Trial.","authors":"Petković-Dabić, Jelena; Binić, Ivana; Carić, Bojana; Božić, Ljiljana; Umičević-Šipka, Sanja; Bednarčuk, Nataša; Dabić, Saša; Šitum, Mirna; Popović-Pejičić, Snježana; Stojiljković, Miloš P; Škrbić, Ranko","year":2025,"journal":"Biomolecules, 15(1)","doi":"10.3390/biom15010046","pmid":"39858442","tags":["semaglutide","glp1-receptor-agonists","skin-dermatology","inflammation-immunity"],"studyType":"randomized-controlled-trial","evidenceStrength":"moderate","keyFinding":"Semaglutide reduced serum pro-inflammatory factors (CRP, cytokines, homocysteine) and improved psoriatic lesion severity in obese patients with type 2 diabetes.","whyItMatters":"Many patients have both diabetes and psoriasis. If semaglutide can treat both simultaneously, it simplifies treatment and addresses the shared inflammatory mechanisms driving both diseases.","specificNumbers":"31 patients: 15 semaglutide + metformin, 16 control (metformin alone). 12-week trial. Psoriasis severity and CRP, cytokines, and homocysteine measured.","methodology":"Open-label, randomized clinical trial investigating semaglutide effects on serum inflammatory markers and psoriasis clinical severity in obese T2D patients.","limitations":"Open-label design — patients and clinicians knew who received semaglutide, potentially biasing assessments. Cannot separate anti-inflammatory effects from weight loss effects on psoriasis."},{"rthcId":"RPEP-13036","title":"Failure of GLP-1 Agonist Therapy to Improve Weight in a 3-Year-Old Patient With Tumor-Related Obesity.","authors":"Petlansky, Rebecca; Graber, Evan","year":2025,"journal":"Case reports in pediatrics, 2025, 1707315","doi":"10.1155/crpe/1707315","pmid":"41323567","tags":["glp1-receptor-agonists","obesity-weight-management","neuropeptides-neuroscience"],"studyType":"case-report","evidenceStrength":"very-low","keyFinding":"Liraglutide up to 3 mg daily failed to improve weight gain in a 3-year-old with tumor-related hypothalamic obesity from a brainstem ganglioglioma, despite good tolerability.","whyItMatters":"Not all obesity responds to GLP-1 drugs. Understanding which types of obesity are resistant helps set appropriate expectations and guides research toward alternative treatments for these patients.","specificNumbers":"Patient: 19-month-old female, ganglioglioma in medulla oblongata (5.5 x 2.6 x 2.3 cm). Liraglutide 0.3 mg titrated to 3 mg daily over 3 months. No GI side effects. Weight continued to increase.","methodology":"Single pediatric case report documenting clinical course of GLP-1 RA therapy for tumor-related hypothalamic obesity.","limitations":"Single case report — cannot determine if other GLP-1 drugs or doses might work. The underlying brain tumor may have progressed during treatment."},{"rthcId":"RPEP-13037","title":"Different formulations of semaglutide and oxidative stress in subjects with type 2 diabetes and MASLD: an open-label, real-life study.","authors":"Petralli, Giovanni; Zoppo, Alice Del; Rovera, Chiara; Raggi, Francesco; Salvati, Antonio; Moriconi, Diego; Distaso, Mariarosaria; Brunetto, Maurizia Rossana; Solini, Anna","year":2025,"journal":"Acta diabetologica, 62(9), 1429-1437","doi":"10.1007/s00592-025-02466-7","pmid":"39954057","tags":["semaglutide","glp1-receptor-agonists","liver-health","diabetes-glucose-metabolism"],"studyType":"observational","evidenceStrength":"low","keyFinding":"Both oral and injectable semaglutide reduced liver inflammation, fibrosis markers, and oxidative stress in T2D patients with MASLD — the first oxidative stress data for semaglutide.","whyItMatters":"Fatty liver disease is increasingly common and can progress to cirrhosis. Showing that both semaglutide formulations reduce oxidative stress adds a new dimension to its liver-protective effects.","specificNumbers":"60 T2D + MASLD patients. 2:1 ratio injectable to oral. 6-month follow-up. Measured transient elastography (CAP), liver enzymes, cytokines, and peroxidation products.","methodology":"Real-life, open-label, prospective study comparing standard doses of injectable vs. oral semaglutide in T2D patients with liver steatosis, measuring liver and systemic inflammation, fibrosis, and oxidative stress markers.","limitations":"Open-label design without blinding. Real-life study without randomization to formulations. Small sample size not specified in abstract."},{"rthcId":"RPEP-13038","title":"AMPed up immunity: 418 whole genomes reveal intraspecific diversity of koala antimicrobial peptides.","authors":"Petrohilos, Cleopatra; Peel, Emma; Silver, Luke W; Belov, Katherine; Hogg, Carolyn J","year":2025,"journal":"Immunogenetics, 77(1), 11","doi":"10.1007/s00251-024-01368-2","pmid":"39779522","tags":["antimicrobial-peptides","inflammation-immunity"],"studyType":"computational","evidenceStrength":"low","keyFinding":"418 koala genomes revealed extensive intraspecific AMP diversity, with marsupial-specific cathelicidin gene expansions providing a large and varied antimicrobial peptide repertoire.","whyItMatters":"Understanding AMP diversity at the population level reveals how species maintain immune defense and could identify novel peptides with therapeutic potential.","specificNumbers":"418 koala whole genomes. Lower allelic diversity in AMPs vs MHC. Balancing selection in PhciDEFB12. Non-synonymous SNPs in active peptides predicted to affect function.","methodology":"Population genomic analysis of 418 whole koala genomes characterizing cathelicidin and defensin gene diversity, genomic organization, and evolutionary patterns.","limitations":"Genomic diversity does not necessarily reflect functional peptide diversity. Predicted AMP sequences need experimental validation for antimicrobial activity."},{"rthcId":"RPEP-13039","title":"Focus on Semaglutide 2.4 mg/week for the Treatment of Metabolic Dysfunction-Associated Steatohepatitis.","authors":"Petta, Salvatore; Kim, KyeongJin; Targher, Giovanni; Romeo, Stefano; Sookoian, Silvia; Zheng, Ming-Hua; Aghemo, Alessio; Valenti, Luca","year":2025,"journal":"Liver international : official journal of the International Association for the Study of the Liver, 45(11), e70407","doi":"10.1111/liv.70407","pmid":"41144918","tags":["semaglutide","glp1-receptor-agonists","liver-health"],"studyType":"narrative-review","evidenceStrength":"strong","keyFinding":"Semaglutide 2.4 mg/week achieved significant improvements in hepatic steatosis, MASH resolution, and fibrosis reduction in phase 2 and 3 trials, leading to conditional US approval.","whyItMatters":"MASH is the most common cause of liver transplantation and had no effective pharmacological treatment until now. Semaglutide's approval changes the treatment landscape for millions of patients with fatty liver disease.","specificNumbers":"Semaglutide 2.4 mg/week SC. Conditional accelerated approval for MASH with F2/F3 fibrosis. Phase 2-3 data show MASH resolution and fibrosis improvement. Consistent cardiovascular and renal benefits.","methodology":"Focused review of phase 2 and 3 clinical trial data supporting the accelerated US approval of semaglutide 2.4 mg/week for MASH with fibrosis.","limitations":"Conditional accelerated approval requires confirmatory trials. Long-term effects on cirrhosis prevention and liver cancer risk reduction are not yet established."},{"rthcId":"RPEP-13040","title":"New Names, New Drugs, Better Outcomes in Steatotic Liver Disease.","authors":"Peverelle, Matthew; Mbelle, Mzamo; Joshi, Deepak","year":2025,"journal":"British journal of hospital medicine (London, England : 2005), 86(8), 1-18","doi":"10.12968/hmed.2024.0655","pmid":"40847981","tags":["glp1-receptor-agonists","liver-health"],"studyType":"narrative-review","evidenceStrength":"moderate","keyFinding":"New MASLD/MASH terminology improves diagnostic clarity, while semaglutide and newer agents offer the first effective pharmacological treatments for this common liver condition.","whyItMatters":"MASLD is now the most common chronic liver disease worldwide. The name change and new treatments represent a paradigm shift in how this condition is understood, diagnosed, and treated.","specificNumbers":"MASLD affects up to 20% of UK adults. Cirrhosis and HCC incidence expected to rise significantly by 2030. Reviews GLP-1 RAs and THR-beta agonists as treatments.","methodology":"Review article covering the evolution of fatty liver disease nomenclature, pathophysiology, and emerging pharmacological treatments.","limitations":"Review article — does not present new data. Treatment landscape is rapidly evolving and some agents are still in clinical trials."},{"rthcId":"RPEP-13041","title":"Youth Perspectives on the Use of Medications for Weight Loss.","authors":"Peyyety, Vaishnavi; Jankowski, Margaret; Apte, Sarah; Sindelar, Jasmine; Elrajabi, Rawan; Chang, Tammy; Sonneville, Kendrin; Vajravelu, Mary Ellen","year":2025,"journal":"The Journal of adolescent health : official publication of the Society for Adolescent Medicine, 77(2), 262-268","doi":"10.1016/j.jadohealth.2025.02.011","pmid":"40266162","tags":["semaglutide","glp1-receptor-agonists","obesity-weight-management"],"studyType":"cross-sectional","evidenceStrength":"low","keyFinding":"Youth ages 14-24 show widespread familiarity with semaglutide for weight loss, with complex attitudes influenced by social media, body image concerns, and potential vulnerability to weight-related discourse.","whyItMatters":"Young people are particularly susceptible to social media messaging about body weight. Understanding their attitudes helps design appropriate public health messaging and clinical guidance around these popular drugs.","specificNumbers":"753 participants, 547 (73%) responded. Average age 20.4. 50.3% female. 73.6% had heard of Ozempic/Wegovy. March 2024 text message poll.","methodology":"Survey of 753 youth participants (ages 14-24) from the MyVoice national panel, using 5 open-ended questions about weight loss medication awareness and opinions.","limitations":"Open-ended survey — responses may not capture the full complexity of youth attitudes. Self-selected panel may not be nationally representative."},{"rthcId":"RPEP-13042","title":"Investigating the Interactions of a Cyclic Peptide Hormone Somatostatin and Its Derivatives on Amyloid-Beta Aggregation.","authors":"Pham, Amy Trinh; Zhao, Yusheng; Oo, Amy; Hefny, Ahmed A; Ganesan, Aravindhan; Rao, Praveen P N","year":2025,"journal":"ACS chemical neuroscience, 16(16), 3115-3126","doi":"10.1021/acschemneuro.5c00044","pmid":"40690368","tags":["somatostatin-analogs","cognitive-health","neuropeptides-neuroscience"],"studyType":"in-vitro","evidenceStrength":"low","keyFinding":"Somatostatin inhibited Aβ42 fibrillogenesis by 91% at 25 μM, outperforming its derivatives octreotide and lanreotide as well as the reference inhibitor orange G (86%).","whyItMatters":"If somatostatin-based peptides can prevent amyloid aggregation, they could represent a new therapeutic approach for Alzheimer's disease using compounds already in clinical use for other conditions.","specificNumbers":"Somatostatin: 91% Abeta42 fibrillogenesis inhibition at 25 mcM. d-Trp8-somatostatin: 74%. Octreotide and lanreotide: ~54%. Reference agent orange G: 86%. Tested at 1, 5, 10, and 25 mcM.","methodology":"In vitro study testing somatostatin, d-Trp8-somatostatin, octreotide, and lanreotide on Aβ42 aggregation kinetics and cytotoxicity in mouse hippocampal HT22 cells.","limitations":"In vitro study — Aβ42 aggregation inhibition in a test tube does not guarantee brain delivery or clinical efficacy. Somatostatin does not easily cross the blood-brain barrier."},{"rthcId":"RPEP-13043","title":"A GLP1R gene variant and sex influence the response to semaglutide treatment in patients with severe obesity.","authors":"Phan, Aurélie; Carette, Claire; Narjoz, Céline; Rives-Lange, Claire; Rassy, Nathalie; Czernichow, Sebastien; Pallet, Nicolas","year":2025,"journal":"Obesity (Silver Spring, Md.), 33(7), 1237-1242","doi":"10.1002/oby.24300","pmid":"40384505","tags":["semaglutide","glp1-receptor-agonists","obesity-weight-management","genetics-genomics"],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"GLP1R rs6923761 GG homozygotes lost 1.64%/month vs. 1.02%/month for AA variants on semaglutide 2.4 mg; sex also influenced response, with women responding better.","whyItMatters":"Pharmacogenomics could help predict which patients will respond best to expensive GLP-1 drugs, improving cost-effectiveness and reducing frustration from non-response.","specificNumbers":"112 patients with BMI >= 40 on semaglutide 2.4 mg weekly for 4+ months. AA (8%): 1.64%/month weight loss. G carriers: 1.04%/month (P = 0.03). Women AA: 1.89%/month vs men G: less than half that rate.","methodology":"Prospective genotyping study of 112 patients with grade 3 obesity treated with semaglutide 2.4 mg weekly for 4+ months, analyzing weight loss kinetics by GLP1R genotype and sex.","limitations":"Small sample (n=112) with only 9 AA genotype patients. Short follow-up (4 months). Single gene variant studied — other variants likely also matter."},{"rthcId":"RPEP-13044","title":"Nano-biohybrids with cell-penetrating peptides: A molecular trojans for glioblastoma precision medicine.","authors":"Phatale, Vivek; Khairnar, Pooja; Shukla, Shalini; Puri, Niharika; Sahane, Prajakta; Srivastava, Saurabh","year":2025,"journal":"International journal of pharmaceutics, 683, 126077","doi":"10.1016/j.ijpharm.2025.126077","pmid":"40819712","tags":["drug-delivery-systems","cancer-oncology","neuropeptides-neuroscience"],"studyType":"narrative-review","evidenceStrength":"moderate","keyFinding":"Nano-biohybrids combining nanocarriers with cell-penetrating peptides show promise for crossing the BBB and delivering therapeutics to glioblastoma tumor cells.","whyItMatters":"Glioblastoma has virtually no effective treatments largely because drugs cannot reach the tumor through the BBB. Cell-penetrating peptide nanocarriers could solve this fundamental delivery problem.","specificNumbers":"Reviews CPP types, nanocarrier designs, BBB and BTB penetration mechanisms, and strategies to overcome instability, degradation, and immunogenicity.","methodology":"Review of nanocarrier-CPP hybrid systems for glioblastoma drug delivery, covering design strategies, BBB penetration mechanisms, and preclinical evidence.","limitations":"Most evidence is preclinical. CPP-nanocarriers face challenges including rapid systemic clearance, potential off-target accumulation, and manufacturing complexity."},{"rthcId":"RPEP-13045","title":"Nutrient-stimulated Hormone-based Therapies: A New Frontier in the Prevention and Management of MASH-associated Hepatocellular Carcinoma.","authors":"Phillips, Richard; Ma, Yuk Ting; Hanif, Wasim; Shah, Tahir; Sivakumar, Shivan","year":2025,"journal":"Journal of clinical and translational hepatology, 13(12), 1060-1066","doi":"10.14218/JCTH.2025.00303","pmid":"41473259","tags":["glp1-receptor-agonists","liver-health","cancer-oncology"],"studyType":"narrative-review","evidenceStrength":"moderate","keyFinding":"GLP-1 receptor agonists and related hormone therapies can resolve MASH without worsening fibrosis, potentially preventing progression to liver cancer.","whyItMatters":"Liver cancer from fatty liver disease is rising rapidly, and effective prevention strategies are urgently needed beyond lifestyle changes alone.","specificNumbers":"Reviews GLP-1 RA effects on MASH resolution, fibrosis, and HCC risk. Observational data suggest reduced liver-related morbidity. Benefits less evident in cirrhosis.","methodology":"Narrative review of clinical and preclinical evidence on nutrient-stimulated hormone therapies for MASLD/MASH and HCC prevention.","limitations":"As a review, it synthesizes existing evidence without generating new data. Long-term cancer prevention outcomes with these therapies remain unproven."},{"rthcId":"RPEP-13046","title":"Tirzepatide-Induced Liver Injury: A Rare Medication Side Effect.","authors":"Phox, Meagan; Thesing, John; Kilgore, W Ransom; Alderson, Joel","year":2025,"journal":"ACG case reports journal, 12(4), e01661","doi":"10.14309/crj.0000000000001661","pmid":"40212859","tags":["tirzepatide","glp1-receptor-agonists","liver-health"],"studyType":"case-report","evidenceStrength":"very-low","keyFinding":"Biopsy-confirmed drug-induced liver injury developed after 8 weeks of tirzepatide use in a 76-year-old woman with concurrent 16-pound weight loss. Mechanism unknown.","whyItMatters":"As tirzepatide is prescribed to millions for diabetes and obesity, even rare side effects must be documented. Liver injury awareness is critical for early detection and intervention.","specificNumbers":"76-year-old woman. 8 weeks of tirzepatide. 16-pound weight loss. Elevated liver enzymes. Biopsy-confirmed DILI.","methodology":"Single case report with liver biopsy confirmation of DILI.","limitations":"Single case; cannot establish incidence or definitive causation. Other potential causes of liver injury may not have been fully excluded. Mechanism unknown."},{"rthcId":"RPEP-13047","title":"Beyond Heart Failure: A Case of Missed Anti-neutrophil Cytoplasmic Antibody (ANCA)-Associated Glomerulonephritis.","authors":"Phyu, Ei Ei; Yit, Chesda; San, Su Su","year":2025,"journal":"Cureus, 17(7), e87973","doi":"10.7759/cureus.87973","pmid":"40821294","tags":["natriuretic-peptides","kidney-renal-health","heart-failure"],"studyType":"case-report","evidenceStrength":"very-low","keyFinding":"ANCA-associated glomerulonephritis was misdiagnosed as cardiorenal syndrome for 8 months, leading to irreversible kidney damage.","whyItMatters":"In elderly patients with multiple conditions, autoimmune kidney disease can hide behind more common diagnoses, and delays in recognition can be devastating.","specificNumbers":"75-year-old female. 8 months of progressive renal decline. MPO-ANCA positive. Renal biopsy: pauci-immune focal proliferative glomerulonephritis. Progressed to dialysis despite cyclophosphamide.","methodology":"Single case report with serological testing and renal biopsy confirmation.","limitations":"Single case report; treatment was initiated late which confounds assessment of therapy effectiveness."},{"rthcId":"RPEP-13048","title":"Incretins (GLP-1 Receptor Agonists) and Polycystic Ovaries.","authors":"Piazza, Mauri José","year":2025,"journal":"JBRA assisted reproduction, 29(4), 800-805","doi":"10.5935/1518-0557.20250162","pmid":"41165218","tags":["glp1-receptor-agonists","reproductive-health","obesity-weight-management","hormones-endocrine"],"studyType":"narrative-review","evidenceStrength":"moderate","keyFinding":"Multiple GLP-1 receptor agonists demonstrated improvements in weight, insulin resistance, and hyperandrogenism in women with PCOS.","whyItMatters":"PCOS has limited treatment options, and a single medication class that addresses weight, insulin resistance, and hormonal imbalance could transform management.","specificNumbers":"Reviews metabolic improvements with different GLP-1 RAs in PCOS patients.","methodology":"Review article summarizing clinical evidence on GLP-1 receptor agonists in PCOS management.","limitations":"Review article — does not present new primary data. Long-term effects on fertility outcomes and pregnancy safety need more research."},{"rthcId":"RPEP-13049","title":"Vertical sleeve gastrectomy and semaglutide have distinct effects on skeletal health and heart function in obese male mice.","authors":"Picoli, Caroline de Carvalho; Tsibulnikov, Sergey; Ho, Mavy; DeMambro, Victoria; Feng, Tiange; Eltahir, May; Le, Phuong T; Chlebek, Carolyn; Rosen, Clifford J; Ryzhov, Sergey; Li, Ziru","year":2025,"journal":"American journal of physiology. Endocrinology and metabolism, 328(4), E555-E566","doi":"10.1152/ajpendo.00521.2024","pmid":"40072928","tags":["semaglutide","glp1-receptor-agonists","obesity-weight-management","bone-joint-health","cardiovascular-health"],"studyType":"animal-study","evidenceStrength":"low","keyFinding":"VSG and semaglutide produced comparable weight loss but had divergent effects on bone mineral density and cardiac function in obese mice.","whyItMatters":"Patients choosing between surgery and GLP-1 drugs need to understand that these approaches may affect bone and heart health differently.","specificNumbers":"Obese male mice. 6 weeks semaglutide vs VSG vs sham/saline controls. Comparable weight loss. Different effects on energy expenditure, bone mineral density (microCT), and heart function (echocardiography).","methodology":"Controlled animal study comparing VSG, semaglutide (6 weeks), and sham/saline controls in obese male mice with micro-CT and indirect calorimetry.","limitations":"Mouse study — metabolic and physiological responses may differ in humans. Only male mice were studied. Short treatment duration."},{"rthcId":"RPEP-13050","title":"A comparative exploration of immunohistochemical markers in patients with papulopustular rosacea undergoing treatment with oral isotretinoin versus doxycycline.","authors":"Picosse, Fabíola; Rocha, Marco Alexandre; Costa, Caroline Sousa; Enokihara, Milvia Maria Simões E Silva; Sanudo, Adriana; Bagatin, Ediléia","year":2025,"journal":"International journal of dermatology, 64(3), 546-551","doi":"10.1111/ijd.17420","pmid":"39097930","tags":["antimicrobial-peptides","skin-dermatology","inflammation-immunity"],"studyType":"randomized-controlled-trial","evidenceStrength":"moderate","keyFinding":"Both isotretinoin and doxycycline effectively reduced cutaneous inflammatory biomarkers in rosacea, but through distinct biological pathways.","whyItMatters":"Understanding how these drugs work at the molecular level helps dermatologists choose the best treatment for individual rosacea patients.","specificNumbers":"40 participants. Doxycycline 100 mg vs isotretinoin 0.3 mg/kg daily. 4-month treatment. VEGF vessel count reduced with doxycycline (P=0.010). VEGF intensity reduced with both. LL-37/cathelicidin expression reduced.","methodology":"Randomized, comparative, evaluator-blinded trial with immunohistochemistry at baseline and 4 months in 40 participants.","limitations":"Relatively small sample (40 patients). 4-month timeframe may not capture long-term effects or relapse patterns."},{"rthcId":"RPEP-13051","title":"Counterregulatory response to hypoglycemia during a hypoglycemic clamp in people with type 2 diabetes treated with tirzepatide.","authors":"Pieber, Thomas R; Svehlikova, Eva; Urva, Shweta; Haupt, Axel; Zhou, Chunmei; Coskun, Tamer; Höller, Vera; Fluhr, Gabriele; Karanikas, Chrisanthi A; Milicevic, Zvonko; Pratt, Edward John","year":2025,"journal":"Frontiers in endocrinology, 16, 1627947","doi":"10.3389/fendo.2025.1627947","pmid":"40964167","tags":["tirzepatide","glp1-receptor-agonists","diabetes-glucose-metabolism"],"studyType":"randomized-controlled-trial","evidenceStrength":"strong","keyFinding":"Tirzepatide 15 mg preserved counterregulatory hormone responses (including glucagon) during induced hypoglycemia, while lowering HbA1c by 1.5%.","whyItMatters":"Confirming that tirzepatide doesn't blunt the body's defense against low blood sugar is critical for its safety in diabetes management.","specificNumbers":"42 participants, crossover design. Tirzepatide 15 mg vs placebo for 12 weeks. HbA1c change: -1.5% vs +0.5%. Nadir PG: 44.5 vs 47.5 mg/dL. Glucagon response not different between groups.","methodology":"Randomized, placebo-controlled crossover study with hypoglycemic clamp testing in 42 participants over 12 weeks.","limitations":"Only tested 15 mg dose. Crossover design requires adequate washout (8-10 weeks provided). Only type 2 diabetes patients studied."},{"rthcId":"RPEP-13052","title":"A qualitative study of the mental health outcomes in people being treated for obesity and type 2 diabetes with glucagon-like peptide-1 receptor agonists.","authors":"Pierret, Aureliane C S; Benton, Madeleine; Sen Gupta, Piya; Ismail, Khalida","year":2025,"journal":"Acta diabetologica, 62(5), 731-742","doi":"10.1007/s00592-024-02392-0","pmid":"39520512","tags":["glp1-receptor-agonists","mental-health-psychiatry","obesity-weight-management"],"studyType":"qualitative","evidenceStrength":"very-low","keyFinding":"Patients experienced both mental health improvements (from weight loss and metabolic gains) and challenges (from side effects and disrupted eating patterns) on GLP-1 medications.","whyItMatters":"Clinical trials focus on physical outcomes, but patients' lived mental health experiences with GLP-1 drugs are equally important for treatment decisions.","specificNumbers":"9 participants interviewed at 12-16 weeks after GLP-1 RA initiation. Three main themes identified through reflexive thematic analysis.","methodology":"Qualitative study using semi-structured interviews with 9 participants, analyzed via reflexive thematic analysis.","limitations":"Small qualitative sample (9 participants) — captures depth but not breadth. Self-selection bias possible."},{"rthcId":"RPEP-13053","title":"PACAP versus CGRP in migraine: From mouse models to clinical translation.","authors":"Pietra, Adriana Della; Kuburas, Adisa; Russo, Andrew F","year":2025,"journal":"Cephalalgia : an international journal of headache, 45(9), 3331024251364242","doi":"10.1177/03331024251364242","pmid":"40931761","tags":["cgrp","neuropeptides-neuroscience","pain-management"],"studyType":"narrative-review","evidenceStrength":"moderate","keyFinding":"CGRP and PACAP play complementary but distinct roles in migraine — CGRP drives trigeminal pain while PACAP primarily influences autonomic symptoms.","whyItMatters":"For patients who don't respond to CGRP-targeted drugs, PACAP may represent an alternative therapeutic pathway.","specificNumbers":"Both peptides elevate cAMP via PKA. PACAP more effective at activating certain pathways. CGRP more abundant in trigeminal system. PACAP more prominent in parasympathetic ganglia.","methodology":"Review comparing preclinical mouse model data and clinical evidence on PACAP and CGRP in migraine pathophysiology.","limitations":"Review relies heavily on preclinical data — PACAP-targeted therapies are earlier in clinical development than CGRP drugs."},{"rthcId":"RPEP-13054","title":"Orforglipron: A Novel Oral GLP-1 Agonist for the Treatment of Obesity and Diabetes.","authors":"Pillai, Ashwin A; Sharma, Ashish M; Krayem, Hussein; Frishman, William H; Aronow, Wilbert S","year":2025,"journal":"Cardiology in review","doi":"10.1097/CRD.0000000000001139","pmid":"41398455","tags":["glp1-receptor-agonists","diabetes-glucose-metabolism","obesity-weight-management"],"studyType":"narrative-review","evidenceStrength":"strong","keyFinding":"Orforglipron 36 mg proved superior to injectable liraglutide in head-to-head Phase 3 trials with ~79% oral bioavailability and no dosing restrictions.","whyItMatters":"Many patients avoid GLP-1 drugs because of injections or oral semaglutide's strict fasting requirements — orforglipron removes both barriers.","specificNumbers":"Orforglipron ~79% oral bioavailability. ACHIEVE-3: HbA1c -2.2% vs -1.4% (oral semaglutide 14 mg). Weight -9.2% vs -5.3%. No food/water restrictions. cAMP stimulation without beta-arrestin recruitment.","methodology":"Review of pharmacology, pharmacokinetics, and Phase 3 clinical trial data (including ACHIEVE-3 head-to-head trial).","limitations":"Review article — long-term safety and real-world effectiveness data are still emerging. Phase 3 trials have limited follow-up."},{"rthcId":"RPEP-13055","title":"Semaglutide: Double-edged Sword with Risks and Benefits.","authors":"Pillarisetti, Lekha; Agrawal, Devendra K","year":2025,"journal":"Archives of internal medicine research, 8(1), 1-13","doi":"10.26502/aimr.0189","pmid":"39902055","tags":["semaglutide","glp1-receptor-agonists","diabetes-glucose-metabolism","obesity-weight-management"],"studyType":"narrative-review","evidenceStrength":"moderate","keyFinding":"Semaglutide provides multi-system benefits (glycemic control, weight loss, cardiovascular protection, potential neuroprotection) but carries risks including pancreatitis and anesthetic complications.","whyItMatters":"With millions now taking semaglutide, both patients and providers need a balanced understanding of its risk-benefit profile.","specificNumbers":"Reviews oral and SC semaglutide. Covers glycemic control, weight loss, cardiovascular risk reduction, potential for Alzheimer disease and PCOS. Risks: pancreatitis, aspiration, AKI, gallbladder, NAION, diabetic retinopathy.","methodology":"Comprehensive narrative review of clinical evidence on semaglutide's mechanisms, benefits, and adverse effects.","limitations":"Narrative review — does not systematically weight evidence quality. Some potential benefits (Alzheimer's, PCOS) are still early-stage."},{"rthcId":"RPEP-13056","title":"The Role of Glucagon-like Peptide-1 Receptor Agonists in Alzheimer's and Parkinson's Disease: A Literature Review of Clinical Trials.","authors":"Pilśniak, Joanna; Węgrzynek-Gallina, Julia; Bednarczyk, Błażej; Buczek, Aleksandra; Pilśniak, Aleksandra; Chmiela, Tomasz; Jarosińska, Agnieszka; Siuda, Joanna; Holecki, Michał","year":2025,"journal":"Life (Basel, Switzerland), 15(12)","doi":"10.3390/life15121893","pmid":"41465832","tags":["glp1-receptor-agonists","cognitive-health","neuropeptides-neuroscience"],"studyType":"narrative-review","evidenceStrength":"moderate","keyFinding":"Human clinical trials show early promise for GLP-1 receptor agonists in neurodegenerative diseases, supported by strong preclinical evidence of neuroprotection.","whyItMatters":"Effective disease-modifying treatments for Alzheimer's and Parkinson's remain elusive — repurposing GLP-1 drugs could accelerate progress.","specificNumbers":"11 clinical trials reviewed. Liraglutide improved brain glucose metabolism and transport in AD. Exenatide showed motor improvements in PD. Preclinical data support anti-inflammatory, antioxidant, and anti-apoptotic effects.","methodology":"Narrative literature review analyzing human clinical trials from Web of Science, Medline, Embase, and ClinicalTrials.gov.","limitations":"Limited number of completed human trials. Narrative review format — not a systematic review with meta-analysis."},{"rthcId":"RPEP-13057","title":"Formyl Peptide Receptors 1 and 2: Essential for Immunomodulation of Crotoxin in Human Macrophages, Unrelated to Cellular Entry.","authors":"Pimenta, Luciana de Araújo; Kato, Ellen Emi; Sobral, Ana Claudia Martins; Duarte, Evandro Luiz; Lamy, Maria Teresa Moura; Pasqualoto, Kerly Fernanda Mesquita; Sampaio, Sandra Coccuzzo","year":2025,"journal":"Cells, 14(15)","doi":"10.3390/cells14151159","pmid":"40801592","tags":["inflammation-immunity","antimicrobial-peptides"],"studyType":"in-vitro","evidenceStrength":"very-low","keyFinding":"Formyl peptide receptors mediate crotoxin's immunomodulatory effects on macrophages but are not involved in its cellular entry mechanism.","whyItMatters":"Understanding how venom toxins interact with immune receptors could inform development of new anti-inflammatory or anti-cancer therapies.","specificNumbers":"THP-1 cells silenced for FPRs or treated with Boc-2. FPR-related signaling (ROS, phagocytosis, spreading) reduced in silenced cells. CTX still entered cells without FPRs.","methodology":"In vitro study using THP-1 cells with FPR gene silencing and pharmacological inhibition (Boc-2 antagonist).","limitations":"In vitro study in a single cell line (THP-1) — may not reflect behavior in all macrophage types or in vivo conditions."},{"rthcId":"RPEP-13058","title":"Brain-infiltrating ILC2s boost poststroke angiogenic initiation through α-CGRP production.","authors":"Ping, An; Yang, Fan; Lu, Lingxiao; Zhang, Xiaotao; Lu, Jianan; Li, Huaming; Gu, Yichen; Jin, Ziyang; Zhang, Jianmin; Shi, Ligen","year":2025,"journal":"The Journal of experimental medicine, 222(11)","doi":"10.1084/jem.20241830","pmid":"40853291","tags":["cgrp","cardiovascular-health","inflammation-immunity","stem-cells-growth-factors"],"studyType":"animal-study","evidenceStrength":"low","keyFinding":"ILC2s infiltrate the brain post-stroke via CXCR1 and produce α-CGRP that initiates angiogenic sprouting, improving long-term functional recovery.","whyItMatters":"Stroke recovery options are limited — harnessing the brain's own immune repair system through ILC2s and CGRP could open new therapeutic pathways.","specificNumbers":"ILC2s enter brain parenchyma via CXCR1 after ischemic stroke. Alpha-CGRP production by ILC2s required for angiogenic sprouting. CGRP-depleted ILC2s failed to initiate angiogenesis. CGRP receptor impairment on endothelial cells abolished the effect.","methodology":"In vivo and in vitro ILC2 expansion studies in ischemic stroke mouse models with functional recovery assessment.","limitations":"Mouse model study — human stroke pathophysiology and immune responses may differ. In vivo ILC2 expansion techniques are not yet clinically available."},{"rthcId":"RPEP-13059","title":"Real-World Comparison of Oral Versus Injectable Semaglutide for the Reduction of Hemoglobin A1C and Weight in Patients with Type 2 Diabetes.","authors":"Pinto, Maria; Brennan, Lillian; Diehl, Katie; Lin, Shally; Heacock, Samantha","year":2025,"journal":"The Journal of pharmacy technology : jPT : official publication of the Association of Pharmacy Technicians, 41(1), 22-31","doi":"10.1177/87551225241289959","pmid":"39545243","tags":["semaglutide","glp1-receptor-agonists","diabetes-glucose-metabolism"],"studyType":"retrospective-cohort","evidenceStrength":"moderate","keyFinding":"First real-world comparison of oral vs. injectable semaglutide for HbA1c and weight reduction in type 2 diabetes patients.","whyItMatters":"Clinicians and patients assume oral and injectable semaglutide are interchangeable, but real-world data to support this has been lacking.","specificNumbers":"Retrospective single-center study. Patients on oral or injectable semaglutide (Nov 2019-Jul 2022). Compared HbA1c and weight changes at 6 months, stratified by dose.","methodology":"Retrospective single-center chart review comparing oral and injectable semaglutide outcomes at 6 months.","limitations":"Retrospective single-center study — subject to selection bias, confounding, and limited generalizability."},{"rthcId":"RPEP-13060","title":"Peptidomics and molecular dynamics on bioactive peptides produced and characterized from the fermented whey of \"Panchali\" sheep of West India.","authors":"Pipaliya, Rinkal; Basaiawmoit, Bethsheba; Sakure, Amar A; Maurya, Ruchika; Bishnoi, Mahendra; Kondepudi, Kanthi Kiran; Tiwary, Bipransh Kumar; Mankad, Maunil; Patil, G B; Gawai, Kunal; Sarkar, Preetam; Hati, Subrota","year":2025,"journal":"Food chemistry, 468, 142466","doi":"10.1016/j.foodchem.2024.142466","pmid":"39689486","tags":["cardiovascular-health","diabetes-glucose-metabolism","inflammation-immunity","peptide-synthesis-chemistry"],"studyType":"in-vitro","evidenceStrength":"very-low","keyFinding":"Fermented sheep whey peptides showed 67-72% inhibition of diabetes and blood pressure-related enzymes, with molecular dynamics confirming stable target binding.","whyItMatters":"Food-derived bioactive peptides could offer natural, functional food approaches to managing diabetes and hypertension.","specificNumbers":"L. plantarum KGL3A fermentation at 37C for 48h. ACE inhibition 71.69%, alpha-amylase 71.32%, alpha-glucosidase 67.14%, lipase 64.15%. Proteolytic activity 9.38 mg/mL. <3 kDa fraction most active. Reduced IL-6, IL-1beta, NO, TNF-alpha.","methodology":"In vitro enzyme inhibition assays, peptidomics, and molecular dynamics simulations of fermented sheep milk peptides.","limitations":"In vitro and computational study — enzyme inhibition in a test tube does not guarantee efficacy in living organisms."},{"rthcId":"RPEP-13061","title":"Production and characterization of anti-hypertensive and anti-diabetic peptides from fermented sheep milk with anti-inflammatory activity: in vitro and molecular docking studies.","authors":"Pipaliya, Rinkal; Basaiawmoit, Bethsheba; Sakure, Amar A; Maurya, Ruchika; Bishnoi, Mahendra; Kondepudi, Kanthi Kiran; Padhi, Srichandan; Rai, Amit Kumar; Liu, Zhenbin; Sarkar, Preetam; Hati, Subrota","year":2025,"journal":"Journal of the science of food and agriculture, 105(8), 4096-4120","doi":"10.1002/jsfa.13617","pmid":"38855927","tags":["cardiovascular-health","diabetes-glucose-metabolism","peptide-synthesis-chemistry"],"studyType":"in-vitro","evidenceStrength":"very-low","keyFinding":"Fermented sheep milk produced peptides with 76% ACE inhibition and ~70% anti-diabetic enzyme inhibition, plus anti-inflammatory properties confirmed in vitro.","whyItMatters":"Dual anti-hypertensive and anti-diabetic activity with anti-inflammatory benefits from a single food source could support functional food development.","specificNumbers":"L. paracasei M11 fermentation. ACE inhibition 76.32%, alpha-amylase 70.13%, alpha-glucosidase 70.11%, lipase 68.22%. Max peptide 9.77 mg/mL at 2.5% inoculation, 48h.","methodology":"In vitro enzyme inhibition, peptide purification and characterization, anti-inflammatory assays, and molecular docking studies.","limitations":"In vitro study — bioavailability, digestive stability, and in vivo efficacy are untested."},{"rthcId":"RPEP-13062","title":"Anti-CGRP monoclonal antibodies counteract establishment of food aversive memories and chemotherapy-induced anorexia and weight loss.","authors":"Pistolesi, Alessandra; Tuniz, Simone; Luceri, Cristina; Molli, Alice; Urru, Matteo; La Rocca, Antonino Iurato; Tanturli, Michele; De Cesaris, Francesco; Buonvicino, Daniela; Chiarugi, Alberto","year":2025,"journal":"Pharmacological research, 217, 107818","doi":"10.1016/j.phrs.2025.107818","pmid":"40490094","tags":["cgrp","cancer-oncology","neuropeptides-neuroscience","gastrointestinal-health"],"studyType":"animal-study","evidenceStrength":"low","keyFinding":"Systemically administered anti-CGRP migraine antibodies reached the brain and counteracted food aversion memories and chemotherapy-induced weight loss in rats.","whyItMatters":"Cancer cachexia and chemotherapy-induced anorexia are devastating — repurposing existing migraine drugs could provide a new treatment avenue.","specificNumbers":"Systemic anti-CGRP mAbs reached rat brain. Counteracted food aversive memories and chemotherapy-induced anorexia/weight loss. Partially reduced fear responses. Unable to prevent liraglutide-induced anorexia.","methodology":"In vivo rat study testing systemic anti-CGRP monoclonal antibodies on food aversion, chemotherapy-induced anorexia, and fear responses.","limitations":"Rat study — brain penetration and behavioral effects may differ in humans. Could not prevent GLP-1 agonist-induced anorexia."},{"rthcId":"RPEP-13063","title":"Biodistribution of atogepant and rimegepant in mouse peripheral and central structures of relevance to migraine pathogenesis.","authors":"Pistolesi, Alessandra; De Cesaris, Francesco; Buonvicino, Daniela; Chiarugi, Alberto","year":2025,"journal":"Cephalalgia : an international journal of headache, 45(11), 3331024251378713","doi":"10.1177/03331024251378713","pmid":"41313225","tags":["cgrp","pain-management"],"studyType":"animal-study","evidenceStrength":"low","keyFinding":"Both atogepant and rimegepant distribute to central migraine-relevant structures including the trigeminal ganglion, brain cortex, and hypothalamus.","whyItMatters":"Understanding where gepants act is crucial for optimizing migraine treatment and developing next-generation CGRP-targeted drugs.","specificNumbers":"Measured in plasma, dura mater, trigeminal ganglion, parietal cortex, and hypothalamus. Compared to oxazepam (brain-permeant reference). Interspecies dose conversion. Single and repeated dosing.","methodology":"Mass spectrometry biodistribution analysis of atogepant and rimegepant in mouse peripheral and central nervous system structures.","limitations":"Mouse biodistribution may not directly translate to human pharmacokinetics. Mass spectrometry measures total drug, not receptor-bound fraction."},{"rthcId":"RPEP-13064","title":"Corticosteroid-dependent increased expression of CGRP and its receptor subunits within the rodent trigeminal ganglion does not prompt cephalic allodynia.","authors":"Pistolesi, Alessandra; Tuniz, Simone; Lapucci, Andrea; Molli, Alice; De Cesaris, Francesco; Landini, Lorenzo; Nassini, Romina; Buonvicino, Daniela; Chiarugi, Alberto","year":2025,"journal":"Cephalalgia : an international journal of headache, 45(11), 3331024251367043","doi":"10.1177/03331024251367043","pmid":"41308054","tags":["cgrp","neuropeptides-neuroscience","pain-management"],"studyType":"animal-study","evidenceStrength":"low","keyFinding":"Corticosteroids upregulated CGRP and receptor expression in the trigeminal system but did not induce head pain, challenging simple CGRP-pain assumptions.","whyItMatters":"This paradoxical finding — more CGRP without more pain — deepens our understanding of what actually triggers migraine and how steroids help.","specificNumbers":"Dexamethasone increased CGRP and RAMP1/CLR expression in rat CA77 cells, SHSY-5Y cells, and human PBMCs. Betamethasone 320 mcg/kg for 10 days in rats and mice. No cephalic allodynia despite increased CGRP.","methodology":"In vitro (cell cultures: CA77, SHSY-5Y, human PBMCs) and in vivo (rat) study examining dexamethasone effects on CGRP/RAMP1/CLR expression.","limitations":"Rodent model — pain assessment in animals has inherent limitations. Acute steroid exposure may differ from chronic clinical use."},{"rthcId":"RPEP-13065","title":"The anti-CGRP mAb Fremanezumab reverts the anti-inflammatory effects of CGRP in vitro but does not alter disease evolution in a mouse model of progressive multiple sclerosis.","authors":"Pistolesi, Alessandra; Molli, Alice; De Cesaris, Francesco; Chiarugi, Alberto; Buonvicino, Daniela","year":2025,"journal":"European journal of pharmacology, 995, 177415","doi":"10.1016/j.ejphar.2025.177415","pmid":"39988092","tags":["cgrp","inflammation-immunity","neuropeptides-neuroscience","pain-management"],"studyType":"animal-study","evidenceStrength":"low","keyFinding":"Fremanezumab reversed CGRP's anti-inflammatory properties in vitro but did not worsen progressive MS disease course in mice.","whyItMatters":"MS patients with migraine need effective treatments — knowing that anti-CGRP drugs don't worsen MS removes a significant prescribing barrier.","specificNumbers":"CGRP inhibited LPS-induced microglia activation and lymphocyte proliferation. Fremanezumab reversed these effects in vitro. NOD mice immunized with MOG35-55 for progressive EAE. Fremanezumab did not alter disease evolution.","methodology":"Combined in vitro immunological assays and in vivo progressive EAE mouse model (NOD mice immunized with MOG35-55).","limitations":"Mouse model of MS may not fully recapitulate human disease. Only one anti-CGRP antibody (fremanezumab) was tested."},{"rthcId":"RPEP-13066","title":"Beyond Diabetes: Semaglutide's Role in Modulating Mood Disorders through Neuroinflammation Pathways.","authors":"Piątkowska-Chmiel, Iwona; Wicha-Komsta, Katarzyna; Pawłowski, Kamil; Syrytczyk, Aleksandra; Kocki, Tomasz; Dudka, Jarosław; Herbet, Mariola","year":2025,"journal":"Cellular and molecular neurobiology, 45(1), 22","doi":"10.1007/s10571-025-01534-4","pmid":"40059125","tags":["semaglutide","glp1-receptor-agonists","mental-health-psychiatry","neuropeptides-neuroscience","diabetes-glucose-metabolism"],"studyType":"animal-study","evidenceStrength":"low","keyFinding":"Semaglutide reduced anxiety and depression in diabetic animal models by modulating the kynurenine pathway and neurobiological markers in the prefrontal cortex.","whyItMatters":"If semaglutide can protect the brain from inflammation-driven mood disorders, it could offer dual benefits for the millions with both diabetes and depression.","specificNumbers":"Evaluated kynurenine pathway and neurobiological markers (GFAP, NEFL, NSE, GAL3) in prefrontal cortex. Also measured peripheral inflammation and stress parameters.","methodology":"Animal model study (diabetic mice) examining behavioral outcomes and neurobiological markers in the prefrontal cortex.","limitations":"Animal study — results may not directly translate to humans. The prefrontal cortex was the only brain region examined."},{"rthcId":"RPEP-13067","title":"A Qualitative Analysis of Patient Experiences Using Semaglutide 2.4 mg for Weight Loss.","authors":"Plenn, Eion; Amin, Dylan; Henry, Jonathan; Leavitt, Gabrielle; Walker, Jason; Soleymani, Taraneh","year":2025,"journal":"Obesity science & practice, 11(4), e70085","doi":"10.1002/osp4.70085","pmid":"40771966","tags":["semaglutide","glp1-receptor-agonists","obesity-weight-management","mental-health-psychiatry"],"studyType":"qualitative","evidenceStrength":"very-low","keyFinding":"Qualitative analysis of 660 Reddit posts provides rich patient narratives about real-world semaglutide 2.4 mg experiences during a period of high demand and shortages.","whyItMatters":"Clinical trials capture efficacy and side effects, but patient forums reveal the full lived experience — access struggles, emotional journey, and real-world challenges.","specificNumbers":"1,000 posts screened from r/WegovyWeightLoss (Oct 2022-Oct 2023). 660 included. 7 themes: efficacy (29.4%), psychosocial impact (22.8%), side effects, access, lifestyle, comparisons, stigma.","methodology":"Retrospective qualitative analysis of 660 Reddit posts from r/WegovyWeightLoss using collaborative codebook development and qualitative coding.","limitations":"Reddit users may not represent all semaglutide patients — skews younger and more tech-savvy. Self-reported data without verification."},{"rthcId":"RPEP-13068","title":"Factors Associated With Semaglutide Initiation Among Adults With Obesity.","authors":"Podolsky, Meghan I; Raquib, Rafeya; Shafer, Paul R; Hempstead, Katherine; Ellis, Randall P; Stokes, Andrew C","year":2025,"journal":"JAMA network open, 8(1), e2455222","doi":"10.1001/jamanetworkopen.2024.55222","pmid":"39836425","tags":["semaglutide","glp1-receptor-agonists","obesity-weight-management"],"studyType":"retrospective-cohort","evidenceStrength":"moderate","keyFinding":"Identified demographic and clinical factors associated with semaglutide initiation for obesity in commercially insured adults without diabetes.","whyItMatters":"Understanding who accesses new obesity medications reveals potential disparities and informs efforts to ensure equitable treatment access.","specificNumbers":"US adults aged 18+ with first obesity diagnosis June 2021-July 2022. Excluded prior AOM, GLP-1, bariatric surgery, or diabetes claims. Continuous enrollment required.","methodology":"Retrospective observational cohort study using MarketScan Commercial Claims and Encounters Database.","limitations":"Only commercially insured patients — excludes Medicare, Medicaid, and uninsured. Observational design cannot establish causation."},{"rthcId":"RPEP-13069","title":"Intranasal Delivery of a Ghrelin Mimetic Engages the Brain Ghrelin Signaling System in Mice.","authors":"Poelman, Renée; Le May, Marie V; Schéle, Erik; Stoltenborg, Iris; Dickson, Suzanne L","year":2025,"journal":"Endocrinology, 166(3)","doi":"10.1210/endocr/bqae166","pmid":"39813130","tags":["growth-hormone-peptides","neuropeptides-neuroscience","drug-delivery-systems"],"studyType":"animal-study","evidenceStrength":"low","keyFinding":"Intranasal GHRP-6 and MK-0677 activated hypothalamic appetite neurons (NPY/AgRP) in mice, confirming brain engagement via nasal delivery.","whyItMatters":"A nasal spray that stimulates appetite could help cancer patients, elderly with wasting, and others who struggle to eat — without needles.","specificNumbers":"GHRP-6 at 5 mg/kg intranasal increased food intake without adverse effects. Activated NPY/AgRP neurons in arcuate nucleus. Ghrelin and MK-0677 intranasal were not effective.","methodology":"In vivo mouse study testing intranasal delivery of ghrelin, GHRP-6, and MK-0677 with assessment of hypothalamic neuron activation.","limitations":"Mouse study — nasal anatomy and drug absorption differ significantly from humans. Long-term efficacy and safety not assessed."},{"rthcId":"RPEP-13070","title":"Novel Cardiometabolic Medications in the Cardiovascular-Kidney-Metabolic Syndrome Era.","authors":"Pohlman, Neal; Patel, Prem N; Essien, Utibe R; Tang, Jasmyn J; Joseph, Joshua J","year":2025,"journal":"The Journal of clinical endocrinology and metabolism, 110(8), 2105-2122","doi":"10.1210/clinem/dgaf295","pmid":"40388382","tags":["glp-1-receptor-agonists","sglt2-inhibitors","cardiovascular-effects","kidney-function"],"studyType":"narrative-review","evidenceStrength":"moderate","keyFinding":"SGLT2 inhibitors and GLP-1 receptor agonists provide multi-organ protection across the cardiovascular-kidney-metabolic syndrome spectrum.","whyItMatters":"Treating these conditions in isolation misses their interconnection — drugs that address multiple organs simultaneously could transform care.","specificNumbers":"No specific effect sizes reported; this is a qualitative synthesis of recent CKM literature.","methodology":"Narrative review synthesizing recent clinical evidence on cardiorenal protective medications in CKM syndrome.","limitations":"Narrative review — does not systematically grade evidence quality. Long-term outcomes for combined therapy approaches are still emerging."},{"rthcId":"RPEP-13071","title":"Real-World Lessons with Fremanezumab as the Third Available CGRP Monoclonal Antibody in a Third-Level Hospital: Focus on the Factors Predicting Response.","authors":"Polanco, Marcos; Gárate, Gabriel; Sánchez-Gudín, Julia; Madera, Jorge; Pascual, Julio; González-Quintanilla, Vicente","year":2025,"journal":"Journal of clinical medicine, 14(4)","doi":"10.3390/jcm14041054","pmid":"40004586","tags":["cgrp-peptides","migraine-headache"],"studyType":"observational","evidenceStrength":"low-moderate","keyFinding":"Fremanezumab significantly reduced headache days in 89 patients, with treatment-naive status among the factors predicting better response.","whyItMatters":"With multiple CGRP antibodies available, knowing which patients respond best to fremanezumab helps personalize migraine prevention.","specificNumbers":"N=89; headache days dropped from 21.1 to 12.4 per quarter; 61.8% achieved >=50% response; 6/10 erenumab non-responders responded to fremanezumab.","methodology":"Prospective observational study tracking headache days one quarter before and after fremanezumab initiation in 89 patients.","limitations":"Single-center observational study with relatively short follow-up (one quarter). No control group."},{"rthcId":"RPEP-13072","title":"Neurohumoral Dysregulation in Acute Myocardial Infarction With Chronic Kidney Disease: Implications for Prognosis and Management.","authors":"Polianska, Oksana; Tashchuk, Victor; Hulaha, Olha; Olinchuk, Valentyna; Moskaliuk, Inna; Kushnir, Yevhen","year":2025,"journal":"Cureus, 17(10), e93692","doi":"10.7759/cureus.93692","pmid":"41049335","tags":["natriuretic-peptides","cardiovascular-effects","biomarkers-diagnostics"],"studyType":"observational","evidenceStrength":"low-moderate","keyFinding":"Reduced kidney function in heart attack patients is associated with elevated RAAS biomarkers and endothelial dysfunction markers that worsen cardiovascular outcomes.","whyItMatters":"Understanding the hormonal crosstalk between failing kidneys and damaged hearts could identify new therapeutic targets and improve risk stratification.","specificNumbers":"N=106; stratified at GFR <=90 vs >90 mL/min; aldosterone and vWF significantly higher in the lower GFR group.","methodology":"Cross-sectional study examining associations between renal function and biomarkers (aldosterone, angiotensin II, vWF) in acute MI patients.","limitations":"Cross-sectional design cannot establish causality. Single time-point biomarker measurements may not capture dynamic changes."},{"rthcId":"RPEP-13073","title":"Beyond Hunger: The Structure, Signaling, and Systemic Roles of Ghrelin.","authors":"Polishchuk, Hlafira; Guzik, Krzysztof; Kantyka, Tomasz","year":2025,"journal":"International journal of molecular sciences, 26(22)","doi":"10.3390/ijms262210996","pmid":"41303478","tags":["ghrelin","growth-hormone-secretagogues","appetite-metabolism"],"studyType":"narrative-review","evidenceStrength":"moderate","keyFinding":"Ghrelin acts as a pleiotropic regulator across feeding, GH release, glucose homeostasis, cardiovascular tone, bone remodeling, immunity, neuroprotection, and addiction. Cryo-EM structures reveal bipartite GHSR1a binding pocket enabling biased signaling. Des-acyl ghrelin and mini-ghrelins have distinct, context-dependent effects. LEAP-2 and GOAT inhibitors are emerging therapeutic strategies.","whyItMatters":"Understanding ghrelin's full scope of activity—far beyond hunger—opens multiple therapeutic avenues. The ghrelin system could be targeted for obesity, inflammatory diseases, neuropsychiatric conditions, and addiction, representing a major druggable axis in the post-GLP-1 era.","specificNumbers":"No specific clinical trial data; reviews structural and functional data from preclinical and clinical literature.","methodology":"Comprehensive narrative review synthesizing structural biology, signaling, physiology, and therapeutic development of the ghrelin system.","limitations":"Narrative review without systematic methodology. Many emerging applications are based on preclinical data. Clinical translation of ghrelin-based therapeutics has been slow despite strong preclinical rationale."},{"rthcId":"RPEP-13074","title":"Surgical Outcomes in Patients with Preoperative GLP-1 Therapy: A Retrospective Analysis.","authors":"Poljo, Adisa; Reichl, Jakob J; Bürgi, Simon; Dirnberger, Amanda S; Schneider, Romano; Klasen, Jennifer M; Billeter, Adrian T; Müller, Beat P; Peterli, Ralph; Kraljević, Marko","year":2025,"journal":"Obesity surgery, 35(9), 3847-3857","doi":"10.1007/s11695-025-08136-5","pmid":"40794223","tags":["glp-1-receptor-agonists","obesity-weight-management"],"studyType":"observational","evidenceStrength":"low-moderate","keyFinding":"Propensity-matched analysis evaluated whether preoperative GLP-1 use affects bariatric surgery outcomes over three years.","whyItMatters":"As more patients try GLP-1 drugs before surgery, knowing whether prior medication use helps or hinders surgical outcomes is critical.","specificNumbers":"N=215 (54 GLP-1, 161 non-GLP-1); pre-op TWL 3.7%; 12-month TWL: 29.8% vs 28.1%; 24-month: 28.9% vs 27.2%; 36-month: 26.9% vs 25.4%.","methodology":"Retrospective cohort with propensity score matching (1:1) comparing preoperative GLP-1 users vs. non-users after RYGB or SG.","limitations":"Retrospective design with potential unmeasured confounders despite propensity matching. Excluded revision surgeries and postoperative GLP-1 use."},{"rthcId":"RPEP-13075","title":"Long-Term Glucagon-Like Peptide 1 Receptor Agonist Use Is Not Associated With Increased Risk of Thyroid Cancer in Adults With Type 2 Diabetes.","authors":"Pollack, Rena; Stokar, Joshua","year":2025,"journal":"Diabetes/metabolism research and reviews, 41(8), e70104","doi":"10.1002/dmrr.70104","pmid":"41182904","tags":["glp-1-receptor-agonists","safety-side-effects","cancer-oncology"],"studyType":"cohort","evidenceStrength":"moderate-high","keyFinding":"No increased thyroid cancer risk was found in 89,646 GLP-1 RA users followed for a median of 4.5 years compared to matched controls on other diabetes drugs.","whyItMatters":"This is one of the largest and longest studies to address the thyroid cancer concern, providing meaningful safety reassurance for millions of GLP-1 users.","specificNumbers":"N=89,646; median follow-up 4.5 +/- 2.3 years; no increased thyroid cancer risk vs insulin, metformin, SGLT2i, DPP-4i, sulfonylureas, or thiazolidinediones.","methodology":"Propensity score matched cohort study using TriNetX electronic health records (2014-2020) with active comparator controls.","limitations":"Observational design — cannot fully exclude residual confounding. Electronic health records may have coding inconsistencies."},{"rthcId":"RPEP-13076","title":"Differential suppression of hippocampal network oscillations by neuropeptide Y.","authors":"Pollali, Evangelia; Draguhn, Andreas","year":2025,"journal":"Neuropharmacology, 266, 110281","doi":"10.1016/j.neuropharm.2024.110281","pmid":"39725122","tags":["neuropeptide-y","neuroprotection-neuroregeneration"],"studyType":"animal-study","evidenceStrength":"low-moderate","keyFinding":"NPY differentially suppresses hippocampal network patterns — strongly inhibiting sharp waves while minimally affecting gamma oscillations.","whyItMatters":"This explains how NPY can reduce fear memory and prevent seizures without broadly disrupting brain function — it selectively targets specific network patterns.","specificNumbers":"Effects measured in C57BL/6 male mouse brain slices; Y2 receptor mediated; CA1 > CA3 effects.","methodology":"In vitro brain slice electrophysiology in C57BL/6 mice using pharmacological tools targeting specific NPY receptor subtypes.","limitations":"In vitro brain slice model — network dynamics in intact brains may differ. Only male mice studied."},{"rthcId":"RPEP-13077","title":"Dermatologic Implications of Glycemic Control Medications for Patients with Type 2 Diabetes Mellitus.","authors":"Ponce, Mayra Betancourt; Shields, Bridget E","year":2025,"journal":"Cutis, 115(1), 7-13","doi":"10.12788/cutis.1148","pmid":"39946251","tags":["glp-1-receptor-agonists","gip-receptor","inflammation-immunology"],"studyType":"narrative-review","evidenceStrength":"low-moderate","keyFinding":"GLP-1 and dual GLP-1/GIP agonists have immune-modulating effects that may benefit inflammatory skin diseases while also causing potential dermatologic side effects.","whyItMatters":"With millions on GLP-1 drugs, dermatologists and endocrinologists need to understand skin-related effects — both beneficial and adverse.","specificNumbers":"No specific trial data reported; qualitative review of case reports and small studies.","methodology":"Narrative review of dermatologic adverse effects and therapeutic benefits of T2DM medications.","limitations":"Narrative review — evidence quality varies. Most dermatologic data comes from case reports and small studies rather than large trials."},{"rthcId":"RPEP-13078","title":"How Bioethics and Reproductive Justice Ought to Inform Glucagon-Like Peptide-1 Receptor Agonists, Research, and Pregnancy.","authors":"Pondugula, Nishita; Merriam, Audrey A","year":2025,"journal":"Obesity reviews : an official journal of the International Association for the Study of Obesity, e70047","doi":"10.1111/obr.70047","pmid":"41271564","tags":["glp-1-receptor-agonists","safety-side-effects","clinical-applications"],"studyType":"policy-analysis","evidenceStrength":"low","keyFinding":"The protectionist exclusion of pregnant people from GLP-1 research creates evidence gaps that may cause more harm than inclusive research would.","whyItMatters":"Without pregnancy data, clinicians must make decisions about GLP-1 drugs in pregnant patients based on absence of evidence rather than evidence of safety.","specificNumbers":"No clinical data presented; this is an ethical and policy analysis.","methodology":"Bioethics analysis applying the protectionist ethic framework and reproductive justice theory to GLP-1 RA research.","limitations":"Theoretical/ethical analysis — does not provide new clinical data on GLP-1 safety in pregnancy."},{"rthcId":"RPEP-13079","title":"Exploring Dietary Intake in Adults with Type 2 Diabetes Using GLP-1 Receptor Agonists: A Cross-Sectional Analysis.","authors":"Ponzo, Valentina; Vitale, Marilena; Bo, Simona; Broglio, Fabio; Goitre, Ilaria; Cioffi, Iolanda","year":2025,"journal":"Nutrients, 17(21)","doi":"10.3390/nu17213318","pmid":"41228390","tags":["glp-1-receptor-agonists","obesity-weight-management","clinical-applications"],"studyType":"observational","evidenceStrength":"low-moderate","keyFinding":"GLP-1 RA users showed differences in dietary intake and Mediterranean diet adherence compared to patients on other diabetes medications.","whyItMatters":"If GLP-1 drugs change dietary patterns, nutritional counseling may need to be adapted to prevent nutrient deficiencies in long-term users.","specificNumbers":"N=103; 50.5% on GLP-1 RAs; fiber ~11 g/1000 kcal; fat ~39-40% of energy; saturated fat <10%.","methodology":"Cross-sectional study of 103 T2D adults using validated food frequency questionnaires and Mediterranean Diet Score.","limitations":"Cross-sectional design cannot determine causation. Single-center Italian cohort may not generalize globally. Self-reported dietary data."},{"rthcId":"RPEP-13080","title":"Health care resource utilization and costs in Medicare Advantage beneficiaries using glucagon-like peptide-1 receptor agonists vs sodium-glucose cotransporter-2 inhibitors.","authors":"Poonawalla, Insiya B; Abdal, Petir; Hayes, Mary; John, Isha; Diaz, Monica; Dixon, Suzanne; Bowe, Andy","year":2025,"journal":"Journal of managed care & specialty pharmacy, 31(7), 627-640","doi":"10.18553/jmcp.2025.31.7.627","pmid":"40577036","tags":["glp-1-receptor-agonists","sglt2-inhibitors","clinical-applications"],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"Retrospective comparison of healthcare costs and resource utilization between GLP-1 RA and SGLT2i initiators in Medicare Advantage patients with type 2 diabetes.","whyItMatters":"With both drug classes recommended as first-line, understanding their cost implications helps inform formulary decisions and value-based care.","specificNumbers":"N=22,167 per group; mean age 68.2; 52.2% female; 73.4% White; no significant differences in inpatient stays, ED visits, or all-cause costs at 12 months.","methodology":"Retrospective cohort study using Humana Medicare Advantage Prescription Drug plan claims data (2018-2022).","limitations":"Claims data cannot capture clinical nuance. Medicare Advantage population may not generalize to commercial or Medicaid populations."},{"rthcId":"RPEP-13081","title":"Epicardial adipose tissue as target of the incretin-based therapies in cardio-metabolic pathologies: a narrative review.","authors":"Pop, Andrea S K; Dănilă, Maria D; Giuchici, Silvia; Buriman, Darius G; Lolescu, Bogdan M; Sturza, Adrian; Muntean, Danina M; Lascu, Ana","year":2025,"journal":"Canadian journal of physiology and pharmacology, 103(6), 182-192","doi":"10.1139/cjpp-2024-0384","pmid":"40048723","tags":["glp-1-receptor-agonists","gip-receptor","cardiovascular-effects"],"studyType":"narrative-review","evidenceStrength":"moderate","keyFinding":"GLP-1 and dual GIP/GLP-1 agonists reduce epicardial adipose tissue volume and inflammatory activity, providing a distinct cardiovascular protection mechanism.","whyItMatters":"EAT is an independent cardiovascular risk factor — drugs that specifically target this dangerous fat depot offer mechanistic benefits beyond weight loss.","specificNumbers":"No specific trial data; reviews mechanistic and imaging studies.","methodology":"Narrative review of preclinical and clinical evidence on incretin therapy effects on epicardial adipose tissue.","limitations":"Narrative review — mechanistic evidence is strong but clinical outcome data specifically linked to EAT reduction are limited."},{"rthcId":"RPEP-13082","title":"Differences in Prevalence and Incidence of Electrocardiogram Abnormalities and Cardiovascular Autonomic Neuropathy Among Randomized Glucose-Lowering Treatments in Early Type 2 Diabetes: The Glycemia Reduction Approaches in Diabetes (GRADE) Cohort.","authors":"Pop-Busui, Rodica; Rosin, Samuel P; Butera, Nicole M; Krause-Steinrauf, Heidi; Abou Assi, Hiba; Garg, Rajesh K; Inzucchi, Silvio E; Katona, Aimee; McGill, Janet B; Mudaliar, Sunder; Schade, David S; Seaquist, Elizabeth R; Tiktin, Margaret; Soliman, Elsayed Z; Green, Jennifer B","year":2025,"journal":"Diabetes care, 48(11), 1960-1970","doi":"10.2337/dc25-1087","pmid":"40986645","tags":["glp-1-receptor-agonists","cardiovascular-effects","clinical-applications"],"studyType":"rct","evidenceStrength":"moderate-high","keyFinding":"Different glucose-lowering drugs showed varying effects on ECG abnormalities and cardiac autonomic neuropathy prevalence over 4 years in the GRADE trial.","whyItMatters":"Heart rhythm problems and autonomic neuropathy are underrecognized diabetes complications — knowing which drugs affect them matters for treatment selection.","specificNumbers":"N=4,769; baseline ECG abnormalities 57.1%; baseline CAN 52.8%; year 4 major ECG abnormalities: liraglutide 9% vs non-liraglutide 13% (P=0.03).","methodology":"Randomized controlled trial (GRADE) with resting ECGs and heart rate variability analysis at baseline, 2, and 4 years in 4,769 participants.","limitations":"ECG analysis was a secondary outcome of the GRADE trial — not powered specifically for this comparison."},{"rthcId":"RPEP-13083","title":"Screening Natriuretic Peptide Levels Predicts Heart Failure and Death in Individuals With Type 1 and Type 2 Diabetes Without Known Heart Failure.","authors":"Pop-Busui, Rodica; Repetto, Enrico; Baron, Jason; Schumacher, Dagmar; Vaduganathan, Muthiah; Pandey, Ambarish","year":2025,"journal":"Diabetes care, 48(12), 2145-2153","doi":"10.2337/dc25-1260","pmid":"41166576","tags":["natriuretic-peptides","biomarkers-diagnostics","cardiovascular-effects"],"studyType":"cohort","evidenceStrength":"moderate-high","keyFinding":"Elevated natriuretic peptide levels in diabetes patients without known heart failure predicted incident heart failure and death.","whyItMatters":"Early detection of heart failure in diabetes could trigger disease-modifying therapies (like SGLT2 inhibitors or GLP-1 drugs) before symptoms appear.","specificNumbers":"N=116,466 (2,990 T1D; 113,476 T2D); ~40% had elevated NP; NT-proBNP 125-300: HR 2.04 (T1D), 2.25 (T2D); NT-proBNP >300: HR 4.48 (T1D), 3.58 (T2D); up to 7-year follow-up.","methodology":"Retrospective cohort using Optum Market Clarity data with multivariable Cox proportional hazard models in 116,466 adults.","limitations":"Retrospective claims-based study — testing was clinically indicated rather than universal screening. Selection bias possible."},{"rthcId":"RPEP-13084","title":"Engineered noncanonical amino acids-based hydrogels for biomedical applications.","authors":"Pophali, Salil; Shrivastava, Vidit; Misra, Rajkumar; Jain, Rahul","year":2025,"journal":"Drug discovery today, 30(7), 104398","doi":"10.1016/j.drudis.2025.104398","pmid":"40494491","tags":["peptide-chemistry-design","drug-delivery-systems"],"studyType":"narrative-review","evidenceStrength":"low-moderate","keyFinding":"Noncanonical amino acids in peptide hydrogels modulate physicochemical properties, enhancing stability, biocompatibility, and functionality for biomedical use.","whyItMatters":"Better hydrogels mean better drug delivery — ncAAs overcome stability limitations that have held back peptide-based therapeutics.","specificNumbers":"No specific clinical data; reviews chemical and materials science literature on ncAA-based hydrogels.","methodology":"Keynote review of chemical and biocatalytic synthesis approaches for ncAA-containing peptide hydrogels.","limitations":"Review focuses on design principles — most applications are preclinical with limited clinical translation data."},{"rthcId":"RPEP-13085","title":"Protease sensitivity and stress adaptation of bioactive peptide-producing lactic acid bacteria: functional implications for food biopreservation.","authors":"Popoola, Oluwabukola Atinuke; Orukotan, Abimbola Ayodeji; Agarry, Olubunmi Olaitan","year":2025,"journal":"BMC biotechnology, 25(1), 143","doi":"10.1186/s12896-025-01077-y","pmid":"41291579","tags":["antimicrobial-peptides","peptide-chemistry-design"],"studyType":"laboratory","evidenceStrength":"low","keyFinding":"13 AMP-producing LAB strains maintained antimicrobial activity across diverse food processing and storage conditions.","whyItMatters":"Natural antimicrobial alternatives to chemical preservatives are urgently needed as consumers demand cleaner food labels.","specificNumbers":"13 strains tested; pH tolerance 4.5-8.5; temperature 20-45C; NaCl 5.5-10%; inhibition zones 5-20 mm; 6 strains 16S rRNA-sequenced; 1 strain with 93.54% identity to nearest known species.","methodology":"In vitro assessment of 13 LAB strains under varied pH, temperature, and NaCl conditions with protease sensitivity testing.","limitations":"In vitro testing — real food matrix conditions may affect AMP activity differently. No specific food application trials described."},{"rthcId":"RPEP-13086","title":"COMBINE 2 is better than one: shaping the future of therapeutics in inadequately controlled type 2 diabetes.","authors":"Popovic, Djordje S; Patoulias, Dimitrios; Koufakis, Theocharis; Papanas, Nikolaos","year":2025,"journal":"Expert review of clinical pharmacology, 18(5), 259-262","doi":"10.1080/17512433.2025.2516784","pmid":"40464480","tags":["glp-1-receptor-agonists","insulin-peptides","clinical-applications"],"studyType":"editorial-commentary","evidenceStrength":"moderate","keyFinding":"IcoSema (weekly insulin icodec + semaglutide) achieved greater HbA1c reduction than semaglutide alone, with similar hypoglycemia risk and GI tolerability but unfavorable weight change, in T2DM patients inadequately controlled on GLP-1 RA therapy.","whyItMatters":"Many diabetes patients eventually need insulin despite GLP-1 therapy. A convenient once-weekly combination injection that improves glycemic control while maintaining the benefits of GLP-1 therapy simplifies treatment intensification and may improve adherence.","specificNumbers":"COMBINE 2 trial data discussed; IcoSema showed greater HbA1c reduction vs semaglutide alone; similar hypoglycemia; unfavorable weight change with IcoSema.","methodology":"Review of the COMBINE 2 randomized clinical trial comparing IcoSema to semaglutide in T2DM patients on GLP-1 RA therapy with or without oral glucose-lowering drugs.","limitations":"Review focused on one trial. Weight trade-off may limit adoption. Long-term outcome data needed. Comparison was against semaglutide alone, not basal-bolus insulin."},{"rthcId":"RPEP-13087","title":"Translating Guidelines into Practice: A Prospective Real-World Study of a Romanian Cohort Treated with GLP-1 RAs.","authors":"Popoviciu, Mihaela Simona; Reurean-Pintilei, Delia; Salmen, Teodor; Rus, Marius; Ferician, Anca; Sava, Cristian; Ardelean, Adriana Ioana; Moroianu, Lavinia-Alexandra; Pantea Stoian, Anca","year":2025,"journal":"Biomedicines, 13(9)","doi":"10.3390/biomedicines13092174","pmid":"41007739","tags":["glp-1-receptor-agonists","obesity-weight-management","clinical-applications"],"studyType":"observational","evidenceStrength":"low-moderate","keyFinding":"All GLP-1 RAs studied improved HbA1c, body weight, and waist circumference in real-world Romanian clinical practice.","whyItMatters":"Clinical trial results don't always translate to real-world settings — this confirms GLP-1 drug effectiveness in routine Romanian clinical practice.","specificNumbers":"N=311; HbA1c >7.2% and BMI >=25 at baseline; all treatments significantly improved HbA1c, BMI, and WC at 6 months (p values significant).","methodology":"Prospective observational study of 311 T2DM adults monitoring HbA1c, body weight, and waist circumference on various GLP-1 RAs.","limitations":"Observational design without control group. Single-country cohort may not generalize to all healthcare settings."},{"rthcId":"RPEP-13088","title":"Antifungal Peptides with Unexpected Structure from a Library of Synthetic Analogs of Host-Defense Peptide Rigin.","authors":"Porras, Marina; Hernández, Dácil; Boto, Alicia","year":2025,"journal":"International journal of molecular sciences, 26(5)","doi":"10.3390/ijms26051900","pmid":"40076526","tags":["antimicrobial-peptides","peptide-chemistry-design"],"studyType":"laboratory","evidenceStrength":"low","keyFinding":"Synthetic rigin analogs with unexpected structures showed potent antifungal activity with minimal antimicrobial resistance induction.","whyItMatters":"With rising antifungal resistance and few new drugs in development, host-defense peptide analogs represent a critically needed new drug class.","specificNumbers":"Library of rigin analogs synthesized from hydroxyproline-containing fragments; potent antifungal activity in N-substituted/protected analogs; no specific MIC values reported in abstract.","methodology":"Peptide library synthesis using hydroxyproline-based building blocks, structural analysis, and antifungal activity screening.","limitations":"In vitro screening — in vivo efficacy, toxicity, and pharmacokinetics not yet assessed."},{"rthcId":"RPEP-13089","title":"Mechanisms of AAV neutralization by human alpha-defensins.","authors":"Porter, Jessica M; Hulce, Kaitlin R; Oswald, Mackenzi S; Busuttil, Kevin; Emmanuel, Shanan N; Bennett, Antonette; McKenna, Robert; Smith, Jason G","year":2025,"journal":"PLoS pathogens, 21(7), e1013283","doi":"10.1371/journal.ppat.1013283","pmid":"40680092","tags":["defensins","antimicrobial-peptides","drug-delivery-systems"],"studyType":"laboratory","evidenceStrength":"low-moderate","keyFinding":"HD5 prevents AAV cell binding while HNP1 neutralizes AAV post-binding — two distinct innate immune mechanisms that limit gene therapy efficacy.","whyItMatters":"Understanding how defensins block AAV helps design gene therapy vectors that evade innate immunity, improving treatment success rates.","specificNumbers":"Both HNP1 and HD5 inhibit AAV2 and AAV6 at low micromolar concentrations; block VP1 unique domain externalization; prevent nuclear entry.","methodology":"In vitro AAV infection assays with purified human defensins HNP1 and HD5, measuring binding, entry, and infection of AAV2 and AAV6.","limitations":"In vitro study — defensin concentrations in relevant tissues in vivo may differ. Only AAV2 and AAV6 serotypes tested."},{"rthcId":"RPEP-13090","title":"Mechanisms of AAV neutralization by human alpha-defensins.","authors":"Porter, Jessica M; Hulce, Kaitlin R; Oswald, Mackenzi S; Busuttil, Kevin; Emmanuel, Shanan N; Bennett, Antonette; McKenna, Robert; Smith, Jason G","year":2025,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2024.09.25.614754","pmid":"39386661","tags":["defensins","antimicrobial-peptides","drug-delivery-systems"],"studyType":"laboratory","evidenceStrength":"low-moderate","keyFinding":"HD5 prevents AAV2/AAV6 cell binding; both HD5 and HNP1 inhibit VP1 unique domain externalization required for endosome escape and nuclear entry; both defensins prevent AAV from reaching the nucleus. This mechanism parallels how defensins neutralize other non-enveloped viruses.","whyItMatters":"AAV-based gene therapy is limited by immune responses. Understanding that innate immune peptides (defensins) block AAV at specific intracellular steps provides actionable targets for engineering improved vectors that can evade these defenses and deliver genes more efficiently.","specificNumbers":"Both defensins active at low micromolar concentrations against AAV2 and AAV6; block VP1 unique domain externalization.","methodology":"In vitro mechanistic study using AAV2 and AAV6 vectors with HNP1 and HD5 defensins, assessing cell binding, VP1 domain externalization, intracellular trafficking, and nuclear localization.","limitations":"In vitro study only. Clinical relevance of defensin-mediated AAV neutralization in patients undergoing gene therapy is not yet established. Only two AAV serotypes and two defensins tested. Defensin concentrations in relevant tissues may vary."},{"rthcId":"RPEP-13091","title":"A Combined Modeling Approach to Predict the Effect of Gastric Emptying Delay on the Pharmacokinetics of Small Molecules.","authors":"Posada, Maria M; Schneck, Karen B; Morse, Bridget L; Rougee, Luc R A; Tham, Lai San; Rehmel, Jessica F; Thompson, Brian; Stamatis, Stephen D; Hall, Stephen D; Dickinson, Gemma L","year":2025,"journal":"CPT: pharmacometrics & systems pharmacology, 14(12), 2026-2039","doi":"10.1002/psp4.70101","pmid":"40842022","tags":["glp-1-receptor-agonists","drug-delivery-systems","clinical-applications"],"studyType":"computational","evidenceStrength":"moderate","keyFinding":"A combined PopPK/PBPK model accurately predicts how dulaglutide-induced gastric emptying delay affects oral drug absorption and pharmacokinetics.","whyItMatters":"Patients on GLP-1 drugs often take multiple medications — predicting drug interactions computationally saves time and money versus running new clinical trials.","specificNumbers":"Model verified against clinical DDI data at low dulaglutide doses; predicted changes in AUC, Cmax, and tmax of co-administered drugs at higher doses.","methodology":"Combined population pharmacokinetic and physiologically-based pharmacokinetic modeling validated against clinical study data.","limitations":"Model predictions require validation for each specific drug combination. May not capture all patient-specific variability."},{"rthcId":"RPEP-13092","title":"Medial hypothalamic MC3R signalling regulates energy rheostasis in adult mice.","authors":"Possa-Paranhos, Ingrid Camila; Butts, Jared; Pyszka, Emma; Nelson, Christina; Congdon, Samuel; Cho, Dajin; Sweeney, Patrick","year":2025,"journal":"The Journal of physiology, 603(2), 379-410","doi":"10.1113/JP286699","pmid":"39718394","tags":["melanocortin-peptides","appetite-metabolism","neuroprotection-neuroregeneration"],"studyType":"animal-study","evidenceStrength":"low-moderate","keyFinding":"MC3R in the medial hypothalamus is required for bi-directional body weight defense — resisting both anabolic and catabolic weight challenges.","whyItMatters":"Understanding how the brain defends body weight could explain why weight loss is so difficult to maintain and inform better obesity treatments.","specificNumbers":"MC3R deleted selectively from medial hypothalamus using viral Cre injection in MC3R-floxed mice; chemogenetic activation/silencing of MC3R neurons in MC3R-Cre mice.","methodology":"Viral Cre-mediated selective MC3R deletion from medial hypothalamus in adult MC3R floxed mice with behavioral assays.","limitations":"Mouse study with viral-mediated deletion — may not perfectly replicate human MC3R physiology. Only one brain region examined."},{"rthcId":"RPEP-13093","title":"Predictors of acute pancreatitis in patients treated with GLP-1 receptor agonists for weight management.","authors":"Postlethwaite, Robert; Amin, Amin M; Alsawas, Rand; Almandoz, Jaime P; Sawas, Tarek","year":2025,"journal":"Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.], 25(5), 609-613","doi":"10.1016/j.pan.2025.06.018","pmid":"40695708","tags":["glp-1-receptor-agonists","safety-side-effects","gastrointestinal-effects"],"studyType":"observational","evidenceStrength":"low-moderate","keyFinding":"Of 2,245 GLP-1 RA users for obesity, 2.2% developed acute pancreatitis; gallstone history and alcohol use were significant predictors.","whyItMatters":"Identifying who is at highest risk for pancreatitis on GLP-1 drugs allows clinicians to make safer prescribing decisions.","specificNumbers":"N=2,245; 49 cases (2.2%); gallstone disease aOR 2.9 (1.6-5.3); prior AP aOR 4.8 (1.8-13.2); CAD/PVD aOR 2.0 (1.01-3.9); tobacco aOR 2.4 (1.2-4.7); BMI 36-40 aOR 0.2 (0.06-0.6).","methodology":"Retrospective case-control study with multivariable logistic regression to identify pancreatitis risk factors.","limitations":"Retrospective design — may miss cases or confounders. Single-center study. The 2.2% rate may reflect the specific patient population."},{"rthcId":"RPEP-13094","title":"Neuroendocrine peritoneal disease and [177Lu]DOTATATE peptide receptor radionuclide therapy: a therapeutic challenge with potential clinical complications.","authors":"Poterszman, Nathan; Baltzinger, Philippe; Mamulashvili Bessac, Darejan; Pham Van, Floriane; Goichot, Bernard; Mertz, Luc; Addeo, Pietro; Brigand, Cecile; Imperiale, Alessio","year":2025,"journal":"European journal of nuclear medicine and molecular imaging, 52(10), 3682-3689","doi":"10.1007/s00259-025-07212-3","pmid":"40183957","tags":["radiolabeled-peptides","cancer-oncology"],"studyType":"observational","evidenceStrength":"low-moderate","keyFinding":"PRRT showed limited response in peritoneal/mesenteric neuroendocrine disease (stable volumes) despite responses in liver metastases, with digestive complication risks.","whyItMatters":"Peritoneal neuroendocrine disease is particularly difficult to treat — understanding PRRT's limitations here guides treatment expectations.","specificNumbers":"N=20; 17 with peritoneal carcinomatosis; functional response rate: PC/MF 18.7% vs liver 38%; 8% of all PRRT patients needed unplanned ED care.","methodology":"Prospective study of 20 patients with sequential [68Ga]DOTATOC PET/CT before, during, and after [177Lu]DOTATATE PRRT.","limitations":"Small sample (20 patients). No control group. Variable disease burden and prior treatments."},{"rthcId":"RPEP-13095","title":"Effect of weight loss and liraglutide on neutrophil gelatinase-associated lipocalin levels among individuals with overweight and knee osteoarthritis: Exploratory analyses of a randomized controlled trial.","authors":"Poulsen, Asbjørn Seenithamby; Stisen, Zara Rebecca; Skougaard, Marie; Christensen, Robin; Overgaard, Anders; Gudbergsen, Henrik; Jacobsen, Stine; Balslev-Clausen, Andreas Peter; Henriksen, Marius; Kristensen, Lars Erik; Bliddal, Henning","year":2025,"journal":"Osteoarthritis and cartilage open, 7(1), 100562","doi":"10.1016/j.ocarto.2024.100562","pmid":"39877802","tags":["glp-1-receptor-agonists","inflammation-immunology","biomarkers-diagnostics"],"studyType":"rct","evidenceStrength":"moderate","keyFinding":"Study evaluated whether diet-induced weight loss and subsequent liraglutide treatment reduce NGAL, a proinflammatory biomarker linked to osteoarthritis.","whyItMatters":"If GLP-1 drugs reduce inflammatory markers driving joint disease, they could address both obesity and osteoarthritis simultaneously.","specificNumbers":"N=168 enrolled, 127 randomized; NGAL rose 93.0 ng/mL (95% CI: 18.9-167.1, P=0.015) after 8-week diet; no difference between liraglutide and placebo at 52 weeks.","methodology":"Secondary analysis of a randomized, double-blind, placebo-controlled trial (8-week LCD + 52-week liraglutide 3 mg vs. placebo).","limitations":"Secondary/exploratory analysis — not powered for NGAL as primary endpoint. Single biomarker does not capture full OA pathophysiology."},{"rthcId":"RPEP-13096","title":"Male sexual dysfunction associated with GLP-1 receptor agonists: a cross-sectional analysis of FAERS data.","authors":"Pourabhari Langroudi, Ashkan; Chen, Abby L; Basran, Satvir; Sommer, Elijah R; Stinson, James; Cheng, Yu-Sheng; Del Giuduce, Francesco; Scott, Michael; Eisenberg, Michael L","year":2025,"journal":"International journal of impotence research, 37(8), 661-667","doi":"10.1038/s41443-025-01061-2","pmid":"40240532","tags":["glp-1-receptor-agonists","safety-side-effects"],"studyType":"pharmacovigilance","evidenceStrength":"low","keyFinding":"FAERS disproportionality analysis found signals of male sexual dysfunction (ED, decreased libido, orgasmic dysfunction) associated with GLP-1 receptor agonists.","whyItMatters":"With millions of men taking GLP-1 drugs, even uncommon sexual side effects affect a large absolute number of patients.","specificNumbers":"182 cases total; exenatide 24.2%, semaglutide 21.4%; ages 40-60 predominant; ROR 0.41 (below 1); chi-squared P<0.0001 but low ROR indicates no disproportionate signal.","methodology":"Cross-sectional pharmacovigilance analysis of FAERS data (Q4 2003 – Q1 2024) using OpenVigil 2.1 with disproportionality measures.","limitations":"FAERS data is spontaneous reporting — cannot establish causation, incidence rates, or control for confounders like obesity and diabetes themselves."},{"rthcId":"RPEP-13097","title":"Reduction of pain and functional disability over time in patients treated with zavegepant: a post-hoc analysis of the BHV3500-301 phase 3 randomized controlled trial.","authors":"Powell, Lauren; O'Sullivan, Fiona; Jayasinghe, Pramoda; Rogula, Basia; Dai, Feng; Cirillo, Jessica; Sweeney, Samantha; Abraham, Lucy; Ailani, Jessica","year":2025,"journal":"The journal of headache and pain, 26(1), 1","doi":"10.1186/s10194-024-01915-y","pmid":"39748312","tags":["cgrp-peptides","migraine-headache","clinical-applications"],"studyType":"rct","evidenceStrength":"moderate-high","keyFinding":"Zavegepant 10 mg nasal spray provided sustained pain reduction and functional improvement over 48 hours versus placebo in acute migraine.","whyItMatters":"A nasal spray CGRP antagonist offers a non-oral, fast-acting option for migraine patients who may have nausea or gastroparesis during attacks.","specificNumbers":"N=1,269 (MNAR analysis); phase 3 trial BHV3500-301; zavegepant 10 mg nasal spray vs placebo; 48-hour assessment across multiple timepoints.","methodology":"Post-hoc analysis of Phase 3 double-blind, randomized, placebo-controlled, single-attack trial (NCT04571060).","limitations":"Post-hoc analysis — not pre-specified endpoint. Single-attack design may not reflect repeated-use outcomes."},{"rthcId":"RPEP-13098","title":"Heart failure with preserved ejection fraction, from pathophysiology to technology tools aim improve patients' management.","authors":"Pozzi, Andrea; Spoladore, Roberto; Iorio, Annamaria; Corrado, Giovanni; D'Amario, Domenico","year":2025,"journal":"Heart failure reviews, 31(1), 3","doi":"10.1007/s10741-025-10585-0","pmid":"41320694","tags":["glp-1-receptor-agonists","sglt2-inhibitors","cardiovascular-effects"],"studyType":"narrative-review","evidenceStrength":"moderate","keyFinding":"SGLT2 inhibitors and GLP-1 receptor agonists show potential benefits in HFpEF management, alongside emerging AI-driven diagnostic and management tools.","whyItMatters":"HFpEF affects millions and has had no effective drug therapies until recently — SGLT2i and GLP-1 drugs could change this.","specificNumbers":"HFpEF accounts for ~50% of all heart failure cases; no specific trial data reported in abstract.","methodology":"Narrative review of HFpEF pathophysiology, pharmacological treatments, and technology-based management approaches.","limitations":"Narrative review — does not systematically assess evidence quality. AI tool benefits are largely theoretical or early-stage."},{"rthcId":"RPEP-13099","title":"Metabolic Cardiovascular Renal Disease (Met-CVRD): A New Nomenclature.","authors":"Pozzilli, Paolo; Messina, Maria Vittoria; Roden, Michael","year":2025,"journal":"Diabetes/metabolism research and reviews, 41(6), e70083","doi":"10.1002/dmrr.70083","pmid":"40888594","tags":["glp-1-receptor-agonists","sglt2-inhibitors","cardiovascular-effects","kidney-function"],"studyType":"narrative-review","evidenceStrength":"low-moderate","keyFinding":"Metabolic dysfunction drives cardiovascular-renal disease and deserves primary positioning in the syndrome nomenclature as Met-CVRD.","whyItMatters":"Naming matters — putting \"metabolic\" first prioritizes upstream treatment of the root cause rather than downstream management of heart and kidney symptoms.","specificNumbers":"No specific trial data; conceptual paper with terminology proposal.","methodology":"Expert commentary/nomenclature proposal with pathophysiological rationale.","limitations":"Expert opinion/nomenclature proposal — no new clinical data. Name adoption requires consensus across multiple specialties."},{"rthcId":"RPEP-13100","title":"Unplanned Emergency Department or Inpatient Acute Care Within 1 Week After Administration of Peptide Receptor Radionuclide Therapy: Frequency of Occurrence and Standard Operating Procedures for Radioprotection in These Situations.","authors":"Prabhu, Roshan S; Russek, Rachel; McBride, James E; Price, Karen B; Garland, Danielle N; Franklin, Elizabeth; McHaffie, Derek R; Ward, Matthew C; Rowland, Chelsea L; Huffstetler, Courtney E; Hicks, Amy S","year":2025,"journal":"Practical radiation oncology, 15(2), e109-e114","doi":"10.1016/j.prro.2024.07.002","pmid":"39053602","tags":["radiolabeled-peptides","cancer-oncology","clinical-applications"],"studyType":"observational","evidenceStrength":"low-moderate","keyFinding":"Unplanned acute care within 7 days of PRRT was characterized in frequency, and a comprehensive radioprotection SOP was developed for these situations.","whyItMatters":"Patients arriving at ERs after PRRT pose radiation safety challenges — having clear protocols protects both patients and healthcare workers.","specificNumbers":"232 patients, 814 infusions; 58% Lutathera, 42% Pluvicto; 19 patients (8%) needed unplanned acute care; 2% of infusions led to ED visits.","methodology":"Retrospective chart review of PRRT patients with development of multidisciplinary radioprotection standard operating procedures.","limitations":"Single-center retrospective review — frequency data may not generalize to all PRRT programs."},{"rthcId":"RPEP-13101","title":"Observation of unique stable nano-assemblies of a lipidated glucagon-like peptide 1 analogue.","authors":"Prada Brichtova, Eva; Gomes Dos Santos, Ana L; Jackson, Sophie E","year":2025,"journal":"Soft matter, 21(47), 9152-9161","doi":"10.1039/d5sm00801h","pmid":"41251522","tags":["glp-1-receptor-agonists","peptide-chemistry-design"],"studyType":"laboratory","evidenceStrength":"low","keyFinding":"A lipidated GLP-1 analog forms unique, stable nano-vesicles through self-assembly, revealing previously unknown behavior in GLP-1 drug chemistry.","whyItMatters":"Understanding how GLP-1 drugs self-assemble at the molecular level could lead to improved drug formulations with better stability and delivery.","specificNumbers":"Assemblies ~21 nm diameter; formed at narrow pH range around 7.0; high alpha-helical content; converted to amyloid fibrils at 37C.","methodology":"Biophysical characterization of peptide self-assembly using structural and imaging techniques.","limitations":"In vitro biophysical study — relevance to in vivo drug behavior needs validation."},{"rthcId":"RPEP-13102","title":"Characterization of Novel ACE-Inhibitory Peptides from Nemopilema nomurai Jellyfish Venom Hydrolysate: In Vitro and In Silico Approaches.","authors":"Prakash, Ramachandran Loganathan Mohan; Ravi, Deva Asirvatham; Hwang, Du Hyeon; Kang, Changkeun; Kim, Euikyung","year":2025,"journal":"Marine drugs, 23(7)","doi":"10.3390/md23070267","pmid":"40710492","tags":["bioactive-peptides","cardiovascular-effects","peptide-chemistry-design"],"studyType":"laboratory","evidenceStrength":"low","keyFinding":"Two jellyfish venom peptides competitively inhibit ACE with IC50 values of 5.68 µM (IGDEPRHQYL) and 23.81 µM (IVGRPLANG), confirmed by molecular dynamics.","whyItMatters":"Marine organisms are an underexplored source of bioactive peptides — jellyfish venom could yield novel antihypertensive drug leads.","specificNumbers":"IVGRPLANG: IC50 23.81 uM, Ki 51.38 uM; IGDEPRHQYL: IC50 5.68 uM, Ki 5.45 uM; both competitive inhibitors.","methodology":"In vitro ACE inhibition kinetics (Lineweaver-Burk), IC50 determination, and molecular dynamics simulations.","limitations":"In vitro and computational study — oral bioavailability, stability in blood, and in vivo efficacy are unknown."},{"rthcId":"RPEP-13103","title":"Comparative Effect of SGLT2 Inhibitors and GLP-1 Agonists on Glycemic Control in Type 2 Diabetes Mellitus.","authors":"Prakash, Ved; Gupta, Sangeeta; Singh, Saumya; Rawat, Anurag; Deshpande, Amit Vasant; Podder, Amrit; Jani, Parth","year":2025,"journal":"Journal of pharmacy & bioallied sciences, 17(Suppl 4), S3244-S3246","doi":"10.4103/jpbs.jpbs_1334_25","pmid":"41522902","tags":["glp-1-receptor-agonists","sglt2-inhibitors","clinical-applications"],"studyType":"rct","evidenceStrength":"low-moderate","keyFinding":"Both drug classes reduced HbA1c significantly over 24 weeks, with GLP-1 agonists showing a slight edge in glycemic control.","whyItMatters":"Head-to-head comparisons between these two leading diabetes drug classes help clinicians choose the best first-line therapy for individual patients.","specificNumbers":"N=120 (60 per group); HbA1c reduction: 1.2% vs 1.3% (P=0.456); GLP-1 group lost more weight; both improved SBP and LDL.","methodology":"Randomized 24-week trial comparing SGLT2 inhibitors vs. GLP-1 agonists in 120 T2DM patients.","limitations":"Small trial (120 patients). The GLP-1 group appears to include DPP-4 inhibitors rather than true GLP-1 RAs, which may confound results."},{"rthcId":"RPEP-13104","title":"Ultrashort Peptide Hydrogels Biomaterials with Potent Antibacterial Activity.","authors":"Pramanik, Bapan; Mukherjee, Payel; Ahmed, Sahnawaz","year":2025,"journal":"Chemistry, an Asian journal, 20(5), e202401137","doi":"10.1002/asia.202401137","pmid":"39688224","tags":["antimicrobial-peptides","peptide-chemistry-design","drug-delivery-systems"],"studyType":"narrative-review","evidenceStrength":"low-moderate","keyFinding":"Ultrashort peptide hydrogels with cationic/hydrophobic design principles show broad-spectrum antibacterial activity through membrane disruption.","whyItMatters":"Antibiotic resistance demands new approaches — peptide hydrogels could serve as next-generation antibacterial materials for wounds and medical devices.","specificNumbers":"Peptides of 2-7 amino acids; broad-spectrum activity against Gram-positive and Gram-negative bacteria; no specific MIC data in abstract.","methodology":"Minireview of peptide hydrogel design, self-assembly mechanisms, and antibacterial testing.","limitations":"Review focused on design principles — most applications are preclinical with limited clinical validation."},{"rthcId":"RPEP-13105","title":"Assessment of cardiovascular event reduction with SGLT2 inhibitors compared to GLP-1 receptor agonists in type 2 diabetes mellitus.","authors":"Prasad Vudathaneni, Vijaya Krishna; Nadella, Swetha Bharathi; Varaprasad Movva, Kalikrishna; Dulipala, Phanindra; Boyapati, Ramanarayana","year":2025,"journal":"Bioinformation, 21(9), 3000-3003","doi":"10.6026/973206300213000","pmid":"41466638","tags":["glp-1-receptor-agonists","sglt2-inhibitors","cardiovascular-effects"],"studyType":"observational","evidenceStrength":"low-moderate","keyFinding":"Retrospective comparison tracked MACE rates between SGLT2i and GLP-1 RA users over 24 months in 300 T2DM patients.","whyItMatters":"Both drug classes have cardiovascular benefits, but direct comparisons help clinicians prioritize the best option for individual patients.","specificNumbers":"N=300 (150 per group); MACE: SGLT2i 11.3% vs GLP-1 RA 15.3% (P=0.182); HbA1c reduction: 1.2% vs 1.3% (P=0.456); HF hospitalization significantly lower with SGLT2i.","methodology":"Retrospective cohort study of 300 patients (150 per group) at a single tertiary center from Jan 2021 to Dec 2023.","limitations":"Retrospective single-center study — subject to selection bias and confounding. Small sample for MACE outcomes."},{"rthcId":"RPEP-13106","title":"Challenges in developing response evaluation criteria for peptide receptor radionuclide therapy: A consensus report from the European Neuroendocrine Tumor Society Advisory Board Meeting 2022 and the ENETS Theranostics Task Force.","authors":"Prasad, Vikas; Koumarianou, Anna; Denecke, Timm; Sundin, Anders; Deroose, Christophe M; Pavel, Marianne; Christ, Emanuel; Lamarca, Angela; Caplin, Martyn; Castaño, Justo P; Dromain, Clarisse; Falconi, Massimo; Grozinsky-Glasberg, Simona; Hofland, Johannes; Knigge, Ulrich Peter; Kos-Kudla, Beata; Krishna, Balkundi A; Reed, Nicholas Simon; Scarpa, Aldo; Srirajaskanthan, Rajaventhan; Toumpanakis, Christos; Kjaer, Andreas; Hicks, Rodney J; Ambrosini, Valentina","year":2025,"journal":"Journal of neuroendocrinology, 37(2), e13479","doi":"10.1111/jne.13479","pmid":"39653582","tags":["radiolabeled-peptides","cancer-oncology","biomarkers-diagnostics"],"studyType":"consensus-statement","evidenceStrength":"moderate","keyFinding":"Expert survey revealed significant variability and unmet needs in PRRT response assessment, with no consensus on standardized criteria.","whyItMatters":"Without standardized response criteria, clinicians cannot reliably compare PRRT outcomes across centers or decide when to stop or modify treatment.","specificNumbers":"70% of Advisory Board responded; 81% from ENETS Centers of Excellence; 13 questions; 46% achieved >75% agreement; 39% achieved >60% agreement.","methodology":"Statement-based survey of ENETS Advisory Board members (70% response rate) with 13 questions and substatements.","limitations":"Expert survey — reflects opinions rather than evidence. Response criteria have not yet been validated prospectively."},{"rthcId":"RPEP-13107","title":"Adjuvant Treatment with Empagliflozin or Semaglutide Increases Endothelial Progenitor Cells in Subjects with Well-Controlled Type 1 Diabetes Mellitus.","authors":"Preložnik Navodnik, Maja; Reberšek, Katarina; Klinar, Katarina; Janež, Andrej; Podgornik, Helena","year":2025,"journal":"Current issues in molecular biology, 47(1)","doi":"10.3390/cimb47010054","pmid":"39852169","tags":["glp-1-receptor-agonists","sglt2-inhibitors","cardiovascular-effects","biomarkers-diagnostics"],"studyType":"rct","evidenceStrength":"moderate","keyFinding":"Both empagliflozin and semaglutide increased endothelial progenitor cells after 12 weeks in well-controlled T1D, suggesting enhanced vascular repair.","whyItMatters":"Vascular damage is a leading cause of complications in T1D — drugs that boost the body's repair capacity could prevent long-term damage.","specificNumbers":"N=83 (empagliflozin 28, semaglutide 29, insulin-only 26); significant EPC increase at 12 weeks in both adjuvant groups; baseline EPCs comparable to healthy controls.","methodology":"Prospective cohort study using flow cytometry to measure CECs and EPCs at baseline and 12 weeks in 83 T1D patients across 3 groups.","limitations":"Small sample sizes per group. Non-randomized design. EPC measurement by flow cytometry has technical variability. Short follow-up."},{"rthcId":"RPEP-13108","title":"A long-term follow-up study of sotatercept for treatment of pulmonary arterial hypertension: interim results of SOTERIA.","authors":"Preston, Ioana R; Badesch, David; Ghofrani, Hossein-Ardeschir; Gibbs, J Simon R; Gomberg-Maitland, Mardi; Hoeper, Marius M; Humbert, Marc; McLaughlin, Vallerie V; Waxman, Aaron B; Manimaran, Solaiappan; Mikhailova, Elina; Reddy, Madhavi; Lau, Anna; de Oliveira Pena, Janethe; Souza, Rogerio","year":2025,"journal":"The European respiratory journal, 66(1)","doi":"10.1183/13993003.01435-2024","pmid":"39978862","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13109","title":"Parallel Temperature Replica-Exchange Molecular Dynamics Simulations Capture the Observed Impact of Stapling on Coiled-Coil Conformational Stability.","authors":"Price, Joshua L","year":2025,"journal":"The journal of physical chemistry. B, 129(3), 866-875","doi":"10.1021/acs.jpcb.4c06974","pmid":"39787564","tags":["peptide-chemistry-design","computational-modeling"],"studyType":"computational","evidenceStrength":"low","keyFinding":"Replica-exchange MD simulations with custom force fields accurately capture the experimentally observed conformational stabilization from peptide stapling.","whyItMatters":"Computational prediction of stapling effects could dramatically accelerate peptide drug development, reducing the need for costly experimental screening.","specificNumbers":"Custom force fields for two triazole staple types; simulations predicted melting temperatures consistent with experimental data for multiple coiled-coil variants.","methodology":"Parallel temperature replica-exchange molecular dynamics with custom force field parameters for nonstandard amino acids and stapling groups.","limitations":"Validated for coiled-coil systems — generalizability to other peptide architectures needs confirmation."},{"rthcId":"RPEP-13110","title":"Considering the use of GLP-1 receptor agonists in women with obesity prior to pregnancy: a narrative review.","authors":"Price, Sarah A L; Nankervis, Alison","year":2025,"journal":"Archives of gynecology and obstetrics, 311(5), 1241-1247","doi":"10.1007/s00404-024-07849-9","pmid":"39762582","tags":["glp-1-receptor-agonists","safety-side-effects","obesity-weight-management"],"studyType":"narrative-review","evidenceStrength":"low-moderate","keyFinding":"GLP-1 drugs are being used off-label for pre-conception weight management, but safety data for this specific context remains limited.","whyItMatters":"With millions of reproductive-age women now taking GLP-1 drugs, understanding pre-conception implications is urgent.","specificNumbers":"No specific efficacy data from pre-conception trials; reviews observational and animal safety data.","methodology":"Narrative review of PubMed, Medline, and Embase literature on GLP-1 RA use before and during pregnancy.","limitations":"Narrative review — evidence base is sparse. Most pregnancy exposure data comes from inadvertent rather than planned use."},{"rthcId":"RPEP-13111","title":"Indirect mitral annuloplasty in patients with reduced or preserved ejection fraction: A real-world, single-centre experience.","authors":"Priebe-Brämer, Holger; Jaly, Firas; Rahunathan, Nithusa; Luedde, Mark; Albert, Alexander; Witte, Klaus K; Hippe, Hans-Joerg","year":2025,"journal":"ESC heart failure, 12(6), 4410-4418","doi":"10.1002/ehf2.70016","pmid":"41255167","tags":["natriuretic-peptides","biomarkers-diagnostics","cardiovascular-effects"],"studyType":"observational","evidenceStrength":"low-moderate","keyFinding":"Carillon device achieved 98.5% implantation success in 204 HF patients, with improved BNP, functional class, and mitral regurgitation at 3 months.","whyItMatters":"Many elderly heart failure patients are too frail for surgery — a minimally invasive 98.5% success rate option fills a critical treatment gap.","specificNumbers":"N=204; age 83+/-6; 68% female; 72% HFrEF; 98.5% implant success; 94% NYHA improvement at 3 months; 91% MR reduction; 10.4% procedural complications.","methodology":"Single-center retrospective study of 204 consecutive patients receiving Carillon device from 2021-2024.","limitations":"Single-center retrospective study. Only 3-month follow-up. No control group."},{"rthcId":"RPEP-13112","title":"Endogenous and exogenous oxytocin modulate interpersonal motor resonance in autism: A context-dependent and person-specific approach.","authors":"Prinsen, Jellina; Alaerts, Kaat","year":2025,"journal":"Autism : the international journal of research and practice, 29(8), 2123-2136","doi":"10.1177/13623613251335730","pmid":"40350658","tags":["oxytocin","neuroprotection-neuroregeneration","clinical-applications"],"studyType":"rct","evidenceStrength":"moderate","keyFinding":"Intranasal oxytocin modulated social motor mirroring in context- and person-dependent ways in autistic and non-autistic men.","whyItMatters":"Understanding how oxytocin affects social cognition in autism — and why it varies between individuals — is crucial for developing personalized therapies.","specificNumbers":"Single dose of 24 IU intranasal oxytocin; measured corticomotor excitability via TMS; person-specific effects modulated by endogenous oxytocin levels.","methodology":"Neurophysiological study using TMS-measured corticomotor excitability after single-dose intranasal oxytocin (24 IU) during social action observation.","limitations":"Only young adult men studied. Single-dose design — chronic effects unknown. TMS is an indirect measure of social processing."},{"rthcId":"RPEP-13113","title":"Broadening the Therapeutic Window of ADCs Using Site-Specific Bioconjugation Showcased by an MMAE-Containing Peptide Linker in a CD79b-Targeting ADC.","authors":"Probst, Philipp; Attinger-Toller, Isabella; Bertrand, Romain; Stark, Ramona; Santimaria, Roger; Schlereth, Bernd; Grabulovski, Dragan; Spycher, Philipp René","year":2025,"journal":"Molecular cancer therapeutics, 24(6), 803-815","doi":"10.1158/1535-7163.MCT-24-0983","pmid":"40177869","tags":["peptide-chemistry-design","cancer-oncology","drug-delivery-systems"],"studyType":"laboratory","evidenceStrength":"low-moderate","keyFinding":"A novel RKAA-peptide linker creates a more stable CD79b-ADC than polatuzumab vedotin, potentially widening the therapeutic window.","whyItMatters":"Better ADC stability means less drug leaks into healthy tissue, potentially reducing severe side effects while maintaining cancer-killing power.","specificNumbers":"Drug-to-antibody ratio of 2; equal efficacy at half payload dose vs polatuzumab vedotin; stable in mouse, cynomolgus, and human sera.","methodology":"Preclinical comparison of RKAA-peptide linked ADC vs. FDA-approved polatuzumab vedotin for stability, efficacy, and safety.","limitations":"Preclinical study — human clinical trial data needed to confirm safety and efficacy advantages."},{"rthcId":"RPEP-13114","title":"Disproportionality analysis on semaglutide and nonarteritic anterior ischemic optic neuropathy in the FDA adverse event reporting system: An emerging pharmacovigilance signal?","authors":"Procacci, Angela; Poluzzi, Elisabetta; De Ponti, Fabrizio; Raschi, Emanuel","year":2025,"journal":"Obesity research & clinical practice, 19(2), 178-180","doi":"10.1016/j.orcp.2025.03.001","pmid":"40133108","tags":["glp-1-receptor-agonists","safety-side-effects"],"studyType":"pharmacovigilance","evidenceStrength":"low-moderate","keyFinding":"Semaglutide showed a disproportionate reporting signal for NAION in FDA adverse event data, even after controlling for diabetes as a confounding indication.","whyItMatters":"NAION causes sudden, often permanent vision loss — if semaglutide increases this risk, millions of users need to be informed.","specificNumbers":"96 NAION cases total; 83 with semaglutide; ROR 17.57 (95% CI 13.93-21.90); median onset 186 days; 53 cases in last 3 months; 18 from Denmark.","methodology":"Pharmacovigilance disproportionality analysis of FAERS data with active-comparator restricted design and therapeutic area analysis.","limitations":"Spontaneous reporting data — cannot establish causation, true incidence, or mechanism. Reporting bias possible due to media attention."},{"rthcId":"RPEP-13115","title":"Weighing the risk of GLP-1 treatment in older adults: Should we be concerned about sarcopenic obesity?","authors":"Prokopidis, Konstantinos; Daly, Robin M; Suetta, Charlotte","year":2025,"journal":"The journal of nutrition, health & aging, 29(10), 100652","doi":"10.1016/j.jnha.2025.100652","pmid":"40819408","tags":["glp-1-receptor-agonists","obesity-weight-management","muscle-bone-joint"],"studyType":"narrative-review","evidenceStrength":"low-moderate","keyFinding":"GLP-1 drug-induced weight loss plus high discontinuation rates create a risk for sarcopenic obesity in older adults through muscle loss and weight cycling.","whyItMatters":"Sarcopenic obesity increases disability, falls, and mortality in older adults — if GLP-1 drugs contribute to it, treatment strategies must be adapted.","specificNumbers":"15-25% weight loss over 12-24 months; up to 2/3 discontinue within 1 year; ~50% reinitiate; sarcopenic obesity prevalence 10-20% in older adults.","methodology":"Expert commentary/narrative review analyzing GLP-1 weight loss, adherence data, and sarcopenic obesity risk.","limitations":"Commentary based on extrapolation from existing data — direct evidence of GLP-1-induced sarcopenic obesity in older adults is limited."},{"rthcId":"RPEP-13116","title":"Functional Polymorphisms in the Neuropeptide Y (NPY) Gene Associated with Egg Production in Thai Native, Black-Bone, and Commercial Laying Hens Using SNP Markers.","authors":"Promket, Doungnapa; Kammongkun, Jennarong; Insee, Jiranan; Kenchaiwong, Wootichai; Pengmeesri, Khanitta; Somchan, Thassawan; Boonkum, Wuttigrai","year":2025,"journal":"Animals : an open access journal from MDPI, 15(5)","doi":"10.3390/ani15050744","pmid":"40076027","tags":["neuropeptide-y","biomarkers-diagnostics"],"studyType":"observational","evidenceStrength":"low","keyFinding":"NPY gene SNP variants were associated with egg production traits including timing of first egg, egg weight, and total production in Thai chickens.","whyItMatters":"Improving egg production in native breeds through genetic markers preserves biodiversity while enhancing food security.","specificNumbers":"N=117 chickens; 6+ SNP loci identified; PIC 0.22-0.50; He 0.26-0.50.","methodology":"SNP genotyping of NPY gene coding sequence in 117 chickens with phenotypic association analysis for 8 egg production traits.","limitations":"Small sample (117 birds). Association does not prove causation. Results may be breed-specific."},{"rthcId":"RPEP-13117","title":"GIP receptor agonism suppresses inflammation-induced aversion and food intake via distinct circuits.","authors":"Province, Haley S; Hayes, Nikolas W; Leong, Nathan A; Lorch, Carolyn M; Pekerman, Alexandra; Xia, Jessica L; Beutler, Lisa R","year":2025,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2025.08.12.669936","pmid":"40832329","tags":["gip-receptor","cgrp-peptides","appetite-metabolism"],"studyType":"animal-study","evidenceStrength":"low-moderate","keyFinding":"GIP receptor agonism blocks IL-1β-induced aversion via parabrachial CGRP neurons while preserving anorexia through a separate circuit.","whyItMatters":"Understanding how GIP separates nausea from appetite suppression could explain why tirzepatide causes less nausea than pure GLP-1 drugs.","specificNumbers":"Mouse study; IL-1-beta used to induce inflammation; parabrachial CGRP neurons required for CTA but not anorexia; dorsal vagal complex GIPR required for anorexia but not anti-aversion.","methodology":"Preclinical mouse study using GIP agonists, IL-1β challenge, in vivo CGRP neuron activity recording, and circuit-specific manipulations.","limitations":"Preprint — not yet peer-reviewed. Mouse study may not fully translate to human experiences of nausea and appetite."},{"rthcId":"RPEP-13118","title":"Effect of video conferencing between primary and secondary care specialists on type 2 diabetes medication.","authors":"Prætorius, Thim; Baymler Lundberg, Anne Sofie; Klausen Fredslund, Eskild; Blach Rossen, Niklas; Gregersen, Søren; Prior, Anders; Søndergaard, Esben; Tang Knudsen, Søren; Sandbæk, Annelli","year":2025,"journal":"NPJ digital medicine, 8(1), 179","doi":"10.1038/s41746-025-01570-w","pmid":"40148532","tags":["glp-1-receptor-agonists","sglt2-inhibitors","clinical-applications"],"studyType":"rct","evidenceStrength":"moderate-high","keyFinding":"RCT tested whether specialist-GP video conferences improved prescribing of recommended diabetes medications including GLP-1 RAs and SGLT2 inhibitors.","whyItMatters":"Evidence-based medications are underused in diabetes — finding scalable ways to close prescribing gaps could improve outcomes for millions.","specificNumbers":"27 of 100 practices randomized; 17.6% difference (95% CI 4.6-30.7%) in GLP-1 RA/SGLT2i prescriptions; minimal differences for ACE/AT2 (-1.1%) and statins (0.0%).","methodology":"Two-arm cluster randomized controlled trial across 27 of 100 general practices in Aarhus, Denmark over 12 months.","limitations":"Cluster randomization with only 27 practices limits power. Danish healthcare system may not generalize to other settings."},{"rthcId":"RPEP-13119","title":"Incretin-based therapies for the management of cardiometabolic disease in the clinic: Past, present, and future.","authors":"Psaltis, James P; Marathe, Jessica A; Nguyen, Mau T; Le, Richard; Bursill, Christina A; Marathe, Chinmay S; Nelson, Adam J; Psaltis, Peter J","year":2025,"journal":"Medicinal research reviews, 45(1), 29-65","doi":"10.1002/med.22070","pmid":"39139038","tags":["glp-1-receptor-agonists","gip-receptor","cardiovascular-effects","obesity-weight-management"],"studyType":"narrative-review","evidenceStrength":"moderate-high","keyFinding":"GLP-1 RAs have evolved from diabetes drugs to multi-organ therapeutics with proven cardiovascular benefits and emerging heart failure and kidney disease applications.","whyItMatters":"This provides the most complete picture of where incretin therapy has been, where it is now, and where it is heading.","specificNumbers":"Reviews phase 3 trial data for GLP-1 RAs and tirzepatide; discusses emerging triple agonists.","methodology":"Comprehensive narrative review published in Medicinal Research Reviews covering mechanisms, clinical trials, and future directions.","limitations":"Narrative review — comprehensive but does not systematically grade all cited evidence."},{"rthcId":"RPEP-13120","title":"First-in-human study of HDM1002, a GLP-1 receptor agonist: Safety, tolerability, pharmacokinetics and pharmacodynamics of escalating single oral doses in healthy volunteers.","authors":"Pu, Junliang; Huang, Yurui; Wan, Lei; Zhu, Mingxue; Wei, Huili; Gao, Hong; Zhong, Liping; Tang, Chengyong; Xu, Junfang","year":2025,"journal":"Diabetes, obesity & metabolism, 27(10), 5622-5631","doi":"10.1111/dom.16610","pmid":"40662378","tags":["glp-1-receptor-agonists","clinical-applications","drug-delivery-systems"],"studyType":"rct","evidenceStrength":"moderate","keyFinding":"HDM1002 was tolerable at doses up to 600 mg in healthy volunteers with predictable GLP-1 class side effects.","whyItMatters":"The race for convenient oral GLP-1 drugs continues — HDM1002 adds another candidate to the pipeline beyond oral semaglutide and orforglipron.","specificNumbers":"N=79; doses 10-600 mg; t1/2 4.99-7.10 hours; dose-proportional Cmax and AUC; no food effect; no serious AEs.","methodology":"First-in-human, randomized, double-blind, placebo-controlled, 2-part study (SAD + food effect) in 79 healthy participants.","limitations":"First-in-human single-dose study — efficacy, chronic dosing safety, and metabolic outcomes not yet assessed."},{"rthcId":"RPEP-13121","title":"Ghrelin-GHSR-LEAP2 system in the pathophysiology of type 2 diabetes.","authors":"Pu, Yueli; Yang, Jianmei; Li, Wei; Wen, Yi; Zheng, Chunmei; Li, Yonglin; Wu, Lijuan; Ming, Yao; Zhao, Changying; Chen, Chen","year":2025,"journal":"iScience, 28(10), 113573","doi":"10.1016/j.isci.2025.113573","pmid":"41069857","tags":["ghrelin","growth-hormone-secretagogues","appetite-metabolism"],"studyType":"narrative-review","evidenceStrength":"moderate","keyFinding":"Ghrelin activates GHSR1a to suppress insulin, induce resistance, and promote hepatic glucose output (worsening diabetes), while LEAP2 antagonizes these effects. Paradoxically, ghrelin also protects against diabetic complications via anti-inflammatory, antioxidant, and anti-apoptotic pathways.","whyItMatters":"Understanding ghrelin's dual role—both harmful (promoting hyperglycemia) and protective (preventing complications)—is essential for designing therapies that block the bad effects while preserving the beneficial ones.","specificNumbers":"No specific clinical data; reviews molecular mechanisms of ghrelin, GHSR, and LEAP2 in T2DM pathophysiology.","methodology":"Narrative review of molecular mechanisms and physiological functions of the ghrelin-GHSR-LEAP2 system in type 2 diabetes.","limitations":"Narrative review. Many mechanistic insights from preclinical models. Clinical translation of ghrelin-axis modulation for diabetes is still early-stage."},{"rthcId":"RPEP-13122","title":"Collagen supplementation in metabolic syndrome: a narrative review unraveling the biological mechanisms and effects.","authors":"Pueyo-Arias, Marián; López-Yoldi, Miguel; Navas-Carretero, Santiago; González-Navarro, Carlos J; Zulet, María de Los Ángeles; Milagro, Fermin I","year":2025,"journal":"Nutrition research reviews, 39, e10","doi":"10.1017/S0954422425100309","pmid":"41424065","tags":["bioactive-peptides","glp-1-receptor-agonists","cardiovascular-effects"],"studyType":"narrative-review","evidenceStrength":"low-moderate","keyFinding":"Collagen peptides show multi-pathway benefits for metabolic syndrome including GLP-1 stimulation, DPP-IV inhibition, ACE inhibition, and AMPK activation.","whyItMatters":"A widely available supplement showing mechanistic benefits across multiple metabolic syndrome components could complement pharmaceutical approaches.","specificNumbers":"No specific clinical trial results; reviews mechanistic data from preclinical and limited human studies.","methodology":"Narrative review integrating human clinical evidence with preclinical mechanistic studies.","limitations":"Narrative review — human evidence is limited and mechanistic data is largely preclinical. Supplement quality varies widely."},{"rthcId":"RPEP-13123","title":"Collagen binding and mimetic peptide-functionalized self-assembled peptide hydrogel enhance chondrogenic differentiation of human mesenchymal stem cells.","authors":"Pulat, Günnur; Gökmen, Oğuzhan; Özcan, Şerife; Karaman, Ozan","year":2025,"journal":"Journal of biomedical materials research. Part A, 113(1), e37786","doi":"10.1002/jbm.a.37786","pmid":"39237470","tags":["peptide-chemistry-design","drug-delivery-systems","muscle-bone-joint"],"studyType":"laboratory","evidenceStrength":"low","keyFinding":"Functionalized SAP hydrogels with collagen-binding and mimetic motifs significantly enhanced chondrogenic differentiation of human MSCs.","whyItMatters":"Millions suffer from cartilage damage with no good repair options — injectable peptide gels that direct stem cells to make cartilage could change that.","specificNumbers":"KLD peptide functionalized with WYRGRL (collagen-binding) and GFOGER (collagen-mimetic); increased DNA, GAG, and collagen content vs plain KLD.","methodology":"In vitro study using SEM characterization and human mesenchymal stem cell culture in functionalized peptide hydrogels.","limitations":"In vitro study — in vivo cartilage repair and long-term durability not yet tested."},{"rthcId":"RPEP-13124","title":"Novel bioactive peptides from ginger rhizome: Integrating in silico and in vitro analysis with mechanistic insights through molecular docking.","authors":"Purohit, Kruttika; Pathak, Rachana; Hayes, Evan; Sunna, Anwar","year":2025,"journal":"Food chemistry, 484, 144432","doi":"10.1016/j.foodchem.2025.144432","pmid":"40279907","tags":["bioactive-peptides","cardiovascular-effects","antimicrobial-peptides"],"studyType":"laboratory","evidenceStrength":"low","keyFinding":"41 bioactive peptides identified from ginger with 4 confirmed to have antioxidant, ACE-inhibitory, and antibacterial activity through in vitro and molecular docking.","whyItMatters":"Discovering bioactive peptides in a common food like ginger could add nutraceutical value and support functional food development.","specificNumbers":"41 bioactive peptides identified; 4 validated in vitro; P4 (IAISPSYPIK) showed potent mixed-type ACE inhibition and bacteriostatic effects.","methodology":"Enzymatic hydrolysis, LC-MS/MS peptide identification, in silico screening, molecular docking, and in vitro validation.","limitations":"In vitro and computational study — oral bioavailability and in vivo activity of ginger peptides are unknown."},{"rthcId":"RPEP-13125","title":"New-Onset Atrial Fibrillation Potentially Associated With Tirzepatide: A Case Report.","authors":"Purvez, Akhtar; Mirza, Mohd; Bashir, Mudhasir","year":2025,"journal":"Cureus, 17(12), e99651","doi":"10.7759/cureus.99651","pmid":"41425685","tags":["glp-1-receptor-agonists","gip-receptor","safety-side-effects","cardiovascular-effects"],"studyType":"case-report","evidenceStrength":"very-low","keyFinding":"New-onset atrial fibrillation requiring intensive care occurred in a patient with no prior cardiac history shortly after starting tirzepatide.","whyItMatters":"While tirzepatide is considered cardioprotective overall, clinicians should watch for rare cardiac rhythm disturbances in newly treated patients.","specificNumbers":"Single case; 62-year-old woman; new-onset AF with rapid ventricular response; resolved after tirzepatide discontinuation.","methodology":"Single case report with comprehensive cardiac and metabolic workup.","limitations":"Single case report — cannot prove causation. Temporal association does not equal causality."},{"rthcId":"RPEP-13126","title":"GLP-1 receptor agonists and GIP/GLP-1 co-agonists in the treatment of obesity in adolescents and the elderly.","authors":"Pérez López, Gilberto","year":2025,"journal":"Medicina clinica, 165(4), 107122","doi":"10.1016/j.medcli.2025.107122","pmid":"40716192","tags":["semaglutide","tirzepatide","glp1-receptor-agonists","obesity-weight-management","aging-longevity"],"studyType":"narrative-review","evidenceStrength":"moderate","keyFinding":"GLP-1 RAs and tirzepatide show promising efficacy and safety in adolescent and elderly obesity populations, though evidence is more limited than in middle-aged adults.","whyItMatters":"Teens and older adults have distinct obesity-related health risks and treatment considerations. Ensuring these medications are safe and effective in these groups is essential for responsible prescribing.","specificNumbers":"Reviews liraglutide, semaglutide, and tirzepatide data in adolescents and elderly. Discusses emerging molecules in development.","methodology":"Review of clinical development, efficacy, safety, and tolerability data for GLP-1 RAs and tirzepatide specifically in adolescent and elderly populations.","limitations":"Limited clinical trial data in both age extremes. Long-term effects on adolescent growth/development and elderly sarcopenia/frailty are not well-studied."},{"rthcId":"RPEP-13127","title":"Could intranasal oxytocin enhance the effects of psychotherapy in individuals with mental disorders? A systematic review and meta-analysis.","authors":"Pérez-Arqueros, Valeska; Soler, Joaquim; Schmidt, Carlos; Vega, Daniel; Pascual, Juan C","year":2025,"journal":"Psychoneuroendocrinology, 171, 107206","doi":"10.1016/j.psyneuen.2024.107206","pmid":"39366103","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13128","title":"Chemical analysis and angiotensin I-converting enzyme inhibitory activity of enzymatic hydrolysates derived from meat of goat-kids with supplemental selenium.","authors":"Pérez-Ramirez, Silvia C; Cruz-Monterrosa, Rosy; Diaz-Ramirez, Mayra; León-Espinosa, Erika B; Aguilar-Toalá, José E; Rosas-Espejel, Monzerrat; Ramirez-Bribiesca, J Efren","year":2025,"journal":"PeerJ, 13, e19261","doi":"10.7717/peerj.19261","pmid":"40292100","tags":["cardiovascular-health","peptide-synthesis-chemistry"],"studyType":"animal-study","evidenceStrength":"very-low","keyFinding":"Selenium supplementation in goat kids enhanced the antioxidant and ACE-inhibitory activity of enzymatic hydrolysates derived from their meat.","whyItMatters":"This shows how animal nutrition can be used to create healthier meat products with built-in blood pressure-lowering peptides, bridging the gap between animal science and functional food development.","specificNumbers":"45 suckling goat kids in 3 groups: control, injectable sodium selenite (0.25 mg/kg), oral selenomethionine (0.3 mg/kg). Evaluated meat composition and ACE-inhibitory activity of enzymatic hydrolysates.","methodology":"Randomized study of 45 suckling goat kids in 3 selenium supplementation groups, with chemical analysis and ACE inhibition testing of enzymatic meat hydrolysates.","limitations":"In vitro ACE inhibition — whether eating selenium-enriched goat meat would actually lower blood pressure in humans is unknown. Peptide bioavailability through digestion needs assessment."},{"rthcId":"RPEP-13129","title":"Efficacy of once-weekly semaglutide in patients with heart failure with preserved ejection fraction, obesity and type 2 diabetes.","authors":"Pérez-Velasco, Miguel A; Bernal-López, Maria-Rosa; Trenas, Alicia; Ricci, Michele; López-Carmona, María-Dolores; García de Lucas, María-Dolores; Gómez-Huelgas, Ricardo; Pérez-Belmonte, Luis M","year":2025,"journal":"Medicina clinica, 165(3), 107019","doi":"10.1016/j.medcli.2025.107019","pmid":"40466271","tags":["semaglutide","glp1-receptor-agonists","heart-failure","obesity-weight-management","diabetes-glucose-metabolism"],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"Once-weekly semaglutide 1.0 mg improved health status and reduced body weight in real-world patients with HFpEF, obesity, and type 2 diabetes versus controls.","whyItMatters":"Real-world evidence confirms that the benefits seen in controlled clinical trials also apply to typical patients seen in everyday medical practice.","specificNumbers":"203 matched patients per group. Primary outcome (>= 5-point KCCQ improvement): 60.6% semaglutide vs 17.7% control (OR 3.99). Semaglutide 1 mg weekly. 24-month follow-up.","methodology":"Prospective, real-world comparative study of patients with HFpEF, obesity, and T2D treated with semaglutide 1.0 mg weekly versus controls not on GLP-1 RAs.","limitations":"Non-randomized design — patients choosing semaglutide may differ from controls in unmeasured ways. Single semaglutide dose studied (1.0 mg, not the higher 2.4 mg obesity dose)."},{"rthcId":"RPEP-13130","title":"Effect of Submaximal Doses of Semaglutide in Patients with Obesity on Metabolic Profile and Serum Levels of Adipocytokines.","authors":"Péč, Martin Jozef; Jurica, Jakub; Péčová, Monika; Nagy, Norbert; Focko, Boris; Miertová, Zuzana; Ferencová, Nikola; Ságová, Ivana; Tonhajzerová, Ingrid; Bolek, Tomáš; Galajda, Peter; Mokáň, Marián; Samoš, Matej","year":2025,"journal":"Pharmaceuticals (Basel, Switzerland), 18(9)","doi":"10.3390/ph18091364","pmid":"41011232","tags":["semaglutide","glp1-receptor-agonists","obesity-weight-management","inflammation-immunity"],"studyType":"observational","evidenceStrength":"low","keyFinding":"Submaximal doses of semaglutide combined with lifestyle modifications improved metabolic markers and obesity-related inflammation biomarkers over 12 weeks.","whyItMatters":"Many patients cannot tolerate maximum semaglutide doses due to side effects. Showing that lower doses still provide metabolic benefits gives clinicians confidence to use doses that patients can actually maintain.","specificNumbers":"32 patients (11 men, 21 women, mean age 49, mean BMI 40.5). 12-week treatment with submaximal semaglutide. Significant reductions in weight, insulin, leptin, ferritin, resistin, IL-6, TNF-alpha, and PAI-1.","methodology":"Prospective observational study of 32 adults (11 men, 21 women; mean BMI 40.5; mean age 49) treated with submaximal semaglutide plus hypocaloric diet and increased physical activity over 12 weeks.","limitations":"Small sample (n=32), no control group, and short 12-week duration. Cannot separate the effects of semaglutide from those of diet and exercise changes."},{"rthcId":"RPEP-13131","title":"Effect of Lipidation on the Structure, Oligomerization, and Aggregation of Glucagon-like Peptide 1.","authors":"Přáda Brichtová, Eva; Edu, Irina A; Li, Xinyang; Becher, Frederik; Gomes Dos Santos, Ana L; Jackson, Sophie E","year":2025,"journal":"Bioconjugate chemistry, 36(3), 401-414","doi":"10.1021/acs.bioconjchem.4c00484","pmid":"39841169","tags":["glp-1-receptor-agonists","peptide-chemistry-design"],"studyType":"laboratory","evidenceStrength":"low-moderate","keyFinding":"Lipidation position and lipid nature significantly influence GLP-1 analog solubility, oligomerization, and long-term physical stability.","whyItMatters":"Physical stability determines whether a peptide drug can be manufactured, stored, and delivered reliably — this data guides next-generation GLP-1 drug design.","specificNumbers":"Five lipidated GLP-1 analogs tested; all showed reduced solubility, increased alpha-helical content, larger oligomeric species vs non-lipidated GLP-1.","methodology":"Systematic biophysical comparison of five lipidated GLP-1 analogs varying in lipidation site and lipid type.","limitations":"In vitro study — stability in formulated drug products may differ from these buffer conditions."},{"rthcId":"RPEP-13132","title":"Prevention of Episodic Migraine Headache Using Pharmacologic Treatments in Outpatient Settings: A Clinical Guideline From the American College of Physicians.","authors":"Qaseem, Amir; Cooney, Thomas G; Etxeandia-Ikobaltzeta, Itziar; Wilt, Timothy J; Harrod, Curtis S; Tice, Jeffrey A; Crandall, Carolyn J; Hicks, Lauri A; Cross, J Thomas; Fitterman, Nick; Lewis, Johanna; Linsky, Amy M; Maroto, Michael; Miller, Matthew C; Obley, Adam J; Owens, Douglas K; Shekelle, Paul G; Shamliyan, Tatyana; Yost, Jennifer","year":2025,"journal":"Annals of internal medicine, 178(3), 426-433","doi":"10.7326/ANNALS-24-01052","pmid":"39899861","tags":["cgrp-peptides","migraine-headache","clinical-applications"],"studyType":"guideline","evidenceStrength":"high","keyFinding":"ACP guidelines provide evidence-based ranking of migraine prevention drugs including CGRP-targeted therapies alongside traditional options.","whyItMatters":"This is a major US guideline — its recommendations will influence prescribing patterns and insurance coverage decisions for millions of migraine patients.","specificNumbers":"Covers 8 drug classes; evaluates comparative effectiveness for episodic migraine (1-14 days/month); uses GRADE methodology.","methodology":"Clinical practice guideline based on systematic reviews of comparative effectiveness, patient values, and economic evidence.","limitations":"Guidelines rely on available evidence, which may be limited for newer agents. Cost-effectiveness varies by healthcare system."},{"rthcId":"RPEP-13133","title":"A hybrid protocol for peptide development: integrating deep generative models and physics simulations for biomolecular design targeting IL23R/IL23.","authors":"Qayyum, Naila; Seo, Hana; Khan, Noman; Manan, Abdul; Ramachandran, Rajath; Haseeb, Muhammad; Kim, Eunha; Choi, Sangdun","year":2025,"journal":"International journal of biological macromolecules, 316(Pt 2), 144652","doi":"10.1016/j.ijbiomac.2025.144652","pmid":"40419055","tags":["peptide-chemistry-design","computational-modeling","inflammation-immunology"],"studyType":"computational","evidenceStrength":"low-moderate","keyFinding":"LSTM-generated peptides with GRU-predicted anti-inflammatory activity showed stable IL-23R binding in molecular dynamics simulations.","whyItMatters":"Peptide drugs targeting IL-23R could be cheaper and more accessible than antibody therapies for common autoimmune diseases.","specificNumbers":"Peptide P4: IC50 = 2 uM; LSTM for generation, GRU for classification, MD for validation; confirmed IL23R specificity.","methodology":"Hybrid computational pipeline: LSTM peptide generation, GRU anti-inflammatory classification, and molecular dynamics simulations.","limitations":"Computational study — designed peptides need experimental synthesis and biological testing."},{"rthcId":"RPEP-13134","title":"The association between glucose-dependent insulinotropic polypeptide and/or glucagon-like peptide-1 receptor agonist prescriptions and substance-related outcomes in patients with opioid and alcohol use disorders: A real-world data analysis.","authors":"Qeadan, Fares; McCunn, Ashlie; Tingey, Benjamin","year":2025,"journal":"Addiction (Abingdon, England), 120(2), 236-250","doi":"10.1111/add.16679","pmid":"39415416","tags":["glp-1-receptor-agonists","gip-receptor","clinical-applications"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"GLP-1/GIP drug prescriptions were associated with reduced opioid overdoses and alcohol intoxications in over 500,000 patients with substance use disorders.","whyItMatters":"The opioid and alcohol crises claim hundreds of thousands of lives — if GLP-1 drugs reduce substance use outcomes, the public health impact could be enormous.","specificNumbers":"N=503,747 OUD patients; N=817,309 AUD patients; 136 US health systems; Jan 2014-Sep 2022; lower incidence of overdose/intoxication with GIP/GLP-1 RA prescriptions.","methodology":"Retrospective cohort study of de-identified EHR data from 136 US health systems (Oracle Cerner), Jan 2014 – Sept 2022.","limitations":"Retrospective observational design — cannot prove causation. Confounding by indication possible (healthier patients may get GLP-1 drugs)."},{"rthcId":"RPEP-13135","title":"Qing-Xin-Jie-Yu Granule attenuates myocardial infarction-induced inflammatory response by regulating the MK2/TTP pathway.","authors":"Qi, Jianghan; Gao, Xiaoyao; Han, Ying; Yang, Meiling; Wei, Chenyi; Zhang, Ling; Chu, Jianfeng","year":2025,"journal":"Pharmaceutical biology, 63(1), 128-140","doi":"10.1080/13880209.2025.2467377","pmid":"39980416","tags":["bioactive-peptides","cardiovascular-effects","inflammation-immunology"],"studyType":"animal-study","evidenceStrength":"low","keyFinding":"QXJYG reduced post-MI inflammation and improved cardiac function by modulating the MK2/TTP anti-inflammatory pathway.","whyItMatters":"Understanding the molecular mechanisms of traditional medicines can validate their use and potentially lead to new drug targets.","specificNumbers":"Mouse MI model (LAD ligation); improved echocardiographic function; reduced serum injury markers; modulated MK2/TTP pathway proteins in vivo and in vitro.","methodology":"Mouse MI model (LAD ligation), in vitro hypoxic H9C2 cells, echocardiography, histology, ELISA, and pathway analysis.","limitations":"Mouse model and cell culture — human clinical trial data for this specific indication is needed. TCM formulation standardization varies."},{"rthcId":"RPEP-13136","title":"Gut microbiota mediates semaglutide attenuation of diabetes-associated cognitive decline.","authors":"Qi, Liqin; Kang, Huimin; Zeng, Feihui; Zhan, Menglan; Huang, Cuihua; Huang, Qintao; Lin, Lijing; He, Guanlian; Liu, Xiaoying; Liu, Xiaohong; Liu, Libin","year":2025,"journal":"Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 22(5), e00615","doi":"10.1016/j.neurot.2025.e00615","pmid":"40413074","tags":["glp-1-receptor-agonists","neuroprotection-neuroregeneration","gut-microbiome"],"studyType":"animal-study","evidenceStrength":"low-moderate","keyFinding":"Semaglutide reversed cognitive impairment and hippocampal damage in diabetic mice, with gut microbiota identified as a key mediating mechanism.","whyItMatters":"If semaglutide protects the brain through gut bacteria, optimizing the microbiome could enhance its neuroprotective effects.","specificNumbers":"Mice received 30 nmol/kg/day semaglutide subcutaneously for 12 weeks; increased beneficial gut bacteria; reduced hippocampal neuroinflammation.","methodology":"Mouse model (HFD + STZ-induced DM) treated with semaglutide 30 nmol/kg daily for 12 weeks with cognitive, histological, and microbiome assessment.","limitations":"Mouse model — human gut microbiota and cognitive mechanisms may differ. Specific bacterial species driving the effect not fully characterized."},{"rthcId":"RPEP-13137","title":"Rational Design of PROTAC Degraders and Their Spatiotemporal Controlled Delivery for Enhanced Tumor Penetration and PD-L1 Protein Degradation.","authors":"Qi, Qianqian; Zhang, Zhanyu; Ji, Xiang; Wang, Dun","year":2025,"journal":"Journal of medicinal chemistry, 68(21), 22665-22688","doi":"10.1021/acs.jmedchem.5c01632","pmid":"41165043","tags":["peptide-chemistry-design","cancer-oncology","drug-delivery-systems"],"studyType":"laboratory","evidenceStrength":"low-moderate","keyFinding":"Cyclic iRGD peptide-engineered PROTAC nanoparticles achieved 67% PD-L1 degradation with enhanced tumor penetration via integrin/neuropilin-1 pathways.","whyItMatters":"Degrading PD-L1 rather than blocking it could provide more durable anti-cancer immunity with lower drug doses and fewer side effects.","specificNumbers":"67.05% PD-L1 degradation at 5 uM over 24 hours; iRGD peptide targets integrin and neuropilin-1; tested in MC38 colon cancer mouse model.","methodology":"Rational PROTAC design, peptide-nanoparticle engineering, and preclinical tumor penetration and efficacy evaluation.","limitations":"Preclinical study — human tumor penetration, safety, and immune response need clinical validation."},{"rthcId":"RPEP-13138","title":"Agonizing GABABR suppresses GLP-1RA's chronotropic effect and reduces post-myocardial infarction arrhythmogenesis.","authors":"Qi, Run; Jingjing, Zhang; Hongchang, Gu; Chenyu, Li; He, Hu; Juan, Li; Yuqin, Zhao; Xiaolin, Wu","year":2025,"journal":"Frontiers in pharmacology, 16, 1616181","doi":"10.3389/fphar.2025.1616181","pmid":"41244817","tags":["glp-1-receptor-agonists","cardiovascular-effects"],"studyType":"animal-study","evidenceStrength":"low-moderate","keyFinding":"GABABR activation suppresses GLP-1 RA chronotropic effects and reduces post-MI arrhythmogenesis through cardiac sympathetic modulation.","whyItMatters":"Understanding how GLP-1 drugs affect heart rhythm could prevent cardiac side effects and open new anti-arrhythmic therapeutic approaches.","specificNumbers":"Mouse MI model (LAD ligation); cardiomyocyte-specific Gabbr1 knockout; heart rate increase independent of sympathetic denervation; GABAB activation reduced post-MI arrhythmias.","methodology":"Cardiomyocyte-specific Gabbr1 knockout mice, MI model, sympathetic denervation, in vivo electrophysiology, and molecular analysis.","limitations":"Mouse model — human cardiac physiology and drug responses may differ. Complex genetic manipulation limits clinical translatability."},{"rthcId":"RPEP-13139","title":"Preclinical evaluation and first-in-human phase 1 trial of AZD0186, a novel, oral small molecule glucagon-like peptide-1 receptor agonist.","authors":"Qi, Weier; Boca, Simina M; Boianelli, Alessandro; Fredberg, Monica; Lundqvist, Sara; Davies, Graeme; Field, Joss; Brighton, Cheryl A; Snijder, Arjan; Grundevik, Pernilla; Eckernäs, Daniel; Träff, Annika Maria; Polla, Magnus; Pettersen, Daniel; Omar, Sami; Hansen, Lars; Janzén, David; Melin, Johanna; van Zuydam, Natalie; Logue, Jennifer; Wallenius, Kristina","year":2025,"journal":"The Journal of pharmacology and experimental therapeutics, 392(10), 103683","doi":"10.1016/j.jpet.2025.103683","pmid":"41015846","tags":["glp-1-receptor-agonists","drug-delivery-systems","clinical-applications"],"studyType":"rct","evidenceStrength":"moderate","keyFinding":"AZD0186 activated GLP-1 receptors, stimulated insulin secretion, and reduced weight in preclinical models, with acceptable Phase 1 human safety.","whyItMatters":"Another oral GLP-1 drug entering the pipeline increases competition, which should improve access and reduce costs for patients.","specificNumbers":"Doses 5-150 mg tested in humans; dose-dependent GSIS in animals and humans; no serious AEs reported.","methodology":"Preclinical (cell lines, EndoC-βH5 cells, NHP, hGLP-1R mice) plus first-in-human randomized single ascending dose trial.","limitations":"Phase 1 single-dose data only — efficacy, chronic safety, and optimal dosing not yet established."},{"rthcId":"RPEP-13140","title":"Effect of Glucagon-Like Peptide 1 Receptor Agonists on Obstructive Sleep Apnea.","authors":"Qian, Bei-Bei; Huang, Yu-Jie; Yan, Cai-Feng; Feng, Shang-Yong; She, Dun-Min","year":2025,"journal":"Obesity science & practice, 11(4), e70090","doi":"10.1002/osp4.70090","pmid":"40860896","tags":["glp-1-receptor-agonists","clinical-applications"],"studyType":"mendelian-randomization","evidenceStrength":"moderate","keyFinding":"Mendelian randomization found a genetic association between GLP-1 receptor activation and reduced obstructive sleep apnea risk.","whyItMatters":"If GLP-1 drugs reduce OSA risk beyond just weight loss, they could address a condition affecting hundreds of millions worldwide.","specificNumbers":"FinnGen R11: 50,200 OSA cases, 401,484 controls; cis-eQTLs for GLP1R gene used as genetic proxies; IVW method primary analysis.","methodology":"Two-sample Mendelian randomization using GLP1R cis-eQTLs as genetic instruments, validated against T2DM and BMI, with FinnGen OSA data.","limitations":"Mendelian randomization assumes genetic instruments are valid proxies for drug effects. Cannot determine the mechanism (weight loss vs direct effect)."},{"rthcId":"RPEP-13141","title":"Hepcidin from the Chinese Spiny Frog (Quasipaa spinosa) Integrates Membrane-Disruptive Antibacterial Activity with Macrophage-Mediated Protection Against Elizabethkingia miricola.","authors":"Qiao, Fen; Qian, Xin-Yi; Feng, Yi-Kai; Chen, Jie","year":2025,"journal":"Genes, 16(12)","doi":"10.3390/genes16121450","pmid":"41465123","tags":["antimicrobial-peptides","inflammation-immunology"],"studyType":"animal-study","evidenceStrength":"low","keyFinding":"Frog hepcidin QsHep combines membrane-disrupting antibacterial activity with macrophage activation for dual protection against E. miricola infection.","whyItMatters":"Dual-function antimicrobial peptides that both kill bacteria and boost immunity represent an ideal therapeutic concept for resistant infections.","specificNumbers":"QsHep tested against multiple pathogens; demonstrated membrane disruption; activated primary macrophages; protective in E. miricola infection model.","methodology":"Gene cloning, tissue expression analysis, synthetic peptide antimicrobial assays, membrane disruption studies, and macrophage immunomodulation testing.","limitations":"Frog-specific pathogen and immune system — relevance to human infections needs evaluation."},{"rthcId":"RPEP-13142","title":"Immunomodulatory effects of QsCATH on macrophages: transcriptomic insights and molecular docking analysis.","authors":"Qiao, Fen; Qian, Xin-Yi; Wu, Jia-Le; Wang, Zi-Xuan; Feng, Yi-Kai; Chen, Jie","year":2025,"journal":"Scientific reports, 15(1), 43728","doi":"10.1038/s41598-025-28482-9","pmid":"41387500","tags":["antimicrobial-peptides","inflammation-immunology"],"studyType":"laboratory","evidenceStrength":"low","keyFinding":"QsCATH suppressed pro-inflammatory cytokines and NF-κB/TNF pathways in macrophages, confirmed by transcriptomics and molecular docking.","whyItMatters":"Natural anti-inflammatory peptides from amphibians could inspire new drugs that fight infection and calm inflammation simultaneously.","specificNumbers":"Downregulated tnf, il6, ccl5, il1b; suppressed NF-kB, TNF, and NOD-like receptor pathways; tested in RAW264.7 macrophages.","methodology":"RNA sequencing of QsCATH-treated RAW264.7 macrophages with KEGG/GO enrichment and molecular docking analysis.","limitations":"In vitro cell culture study — in vivo efficacy, toxicity, and pharmacokinetics are unknown."},{"rthcId":"RPEP-13143","title":"Intrinsically Disordered Peptide Nanofibers from a Structured Motif Within Proteins.","authors":"Qiao, Yuchen; Zia, Ayisha; Shy, Adrianna; Wu, Grace; Chu, Matthew; Liu, Zhiyu; Wang, Fengbin; Xu, Bing","year":2025,"journal":"Angewandte Chemie (International ed. in English), 64(27), e202425456","doi":"10.1002/anie.202425456","pmid":"40294067","tags":["peptide-chemistry-design","drug-delivery-systems"],"studyType":"laboratory","evidenceStrength":"low","keyFinding":"Phosphorylated octapeptides combining a kinase site with a self-assembling motif form enzyme-responsive intrinsically disordered nanofibers.","whyItMatters":"Enzyme-responsive peptide nanofibers could serve as biosensors or drug delivery systems that activate in response to specific cellular conditions.","specificNumbers":"Phosphorylated octapeptide; forms hydrogel upon dephosphorylation; cryo-EM confirmed intrinsically disordered nanofiber structure.","methodology":"Peptide synthesis, self-assembly characterization, structural analysis, and enzymatic responsiveness testing.","limitations":"Proof-of-concept study — practical applications need development and biological testing."},{"rthcId":"RPEP-13144","title":"Efficacy of ticagrelor and clopidogrel in treating unstable angina and their effects on serum inflammatory factors.","authors":"Qin, Donghui; Ren, Yuanyuan; Zhang, Na; Yang, Xue; Chen, Zhuo; Zhao, Changliang","year":2025,"journal":"Pakistan journal of pharmaceutical sciences, 38(1), 77-82","doi":null,"pmid":"40089933","tags":["natriuretic-peptides","biomarkers-diagnostics","cardiovascular-effects"],"studyType":"rct","evidenceStrength":"low-moderate","keyFinding":"Ticagrelor was superior to clopidogrel for angina symptoms and inflammatory marker reduction in unstable angina patients.","whyItMatters":"Choosing the right antiplatelet drug affects not just clotting but also the inflammatory processes driving coronary disease.","specificNumbers":"Ticagrelor vs clopidogrel; lower BNP, CRP, IL-6, IL-18, MMP-9, TNF-alpha, and multiple other markers in the ticagrelor group (all P<0.05).","methodology":"Comparative clinical study measuring angina symptoms and a comprehensive inflammatory biomarker panel.","limitations":"Single study — specific methodology not detailed in abstract. Inflammatory markers are secondary to clinical outcomes."},{"rthcId":"RPEP-13145","title":"Biomimetic chitosan derivatives inspired by cell-penetrating peptides for enhanced octreotide absorption following lung delivery.","authors":"Qin, Lu; Cui, Zhixiang; Zhang, Ziwei; Zhai, Qiyao; Wu, Yu; Guan, Jian; Xu, Enyu; Zhang, Xin; Mao, Shirui","year":2025,"journal":"Carbohydrate polymers, 369, 124251","doi":"10.1016/j.carbpol.2025.124251","pmid":"40973249","tags":["drug-delivery-systems","peptide-chemistry-design","clinical-applications"],"studyType":"animal-study","evidenceStrength":"low-moderate","keyFinding":"Amino acid-modified chitosan enhanced octreotide absorption across lung epithelium in an amino acid type-dependent manner in cells and rats.","whyItMatters":"Inhaled peptide drugs could replace injections for conditions like neuroendocrine tumors, improving patient compliance and quality of life.","specificNumbers":"Arginine-chitosan showed highest absorption enhancement among tested AA-CSs; tested in 3D Transwell models and Sprague Dawley rats.","methodology":"Synthesis of amino acid-chitosan copolymers, 3D Transwell cell models, and Sprague Dawley rat lung delivery studies.","limitations":"Rat lung physiology differs from human. Long-term safety of modified chitosan in lungs needs assessment."},{"rthcId":"RPEP-13146","title":"Goldfish phoenixin: (I) structural characterization, tissue distribution, and novel function as a feedforward signal for feeding-induced food intake in fish model.","authors":"Qin, Xiangfeng; Ye, Cheng; Chan, Ying Wai; Wong, Anderson O L","year":2025,"journal":"Frontiers in endocrinology, 16, 1570716","doi":"10.3389/fendo.2025.1570716","pmid":"40365230","tags":["bioactive-peptides","appetite-metabolism"],"studyType":"animal-study","evidenceStrength":"low","keyFinding":"Phoenixin acts as a feedforward appetite signal in goldfish — feeding increases PNX expression, which in turn stimulates additional food intake.","whyItMatters":"Understanding feedforward appetite signals may explain binge eating mechanisms and could identify new targets for appetite control.","specificNumbers":"Two PNX isoforms and one GPR173 cloned; both IP and ICV injection of PNX20a/b increased food intake; expression rose after feeding, fell with fasting.","methodology":"Gene cloning, tissue expression (RT-PCR), phylogenetic analysis, in silico modeling, and feeding experiments in goldfish.","limitations":"Fish model — feedforward mechanisms may differ in mammals. Single species studied."},{"rthcId":"RPEP-13147","title":"Autonomic nervous system imbalance in diabetic mouse choroids.","authors":"Qin, Yuan-Jun; Zhang, Yong-Chao; Lin, Yunru; Hong, Yiyi; Sun, Xufang; Xu, Fan; Chen, Changzheng","year":2025,"journal":"Tissue & cell, 94, 102798","doi":"10.1016/j.tice.2025.102798","pmid":"39970774","tags":["neuropeptide-y","cgrp-peptides","vip-related-peptides"],"studyType":"animal-study","evidenceStrength":"low","keyFinding":"Diabetes caused autonomic nerve fiber damage and altered CGRP, NPY, VIP, and neurotransmitter enzyme levels in mouse choroids.","whyItMatters":"Choroidal blood flow dysfunction contributes to diabetic retinopathy — understanding the nerve imbalance driving it could enable new treatments.","specificNumbers":"Streptozotocin diabetic mice; altered NPY, CGRP, VIP, TH, ChAT, nNOS in choroid; nerve fiber damage on TEM; changes in SCG and TG ganglia.","methodology":"STZ-induced diabetic mouse model with TEM imaging, mass spectrometry, western blot, qRT-PCR, and immunofluorescence.","limitations":"Mouse model — human diabetic choroidopathy may involve additional factors. Single timepoint assessment."},{"rthcId":"RPEP-13148","title":"FcγR-targeted tuftsin clusters rejuvenate macrophages in preclinical sepsis-associated secondary infection.","authors":"Qing, Guangchao; Zhang, Yuxuan; Wang, Yongchao; Li, Xianlei; Luo, Ting; Zhang, Fuxue; Ni, Qiankun; Hu, Runjing; Shan, Shaobo; Zhang, Hong; Yuan, Rui; Gan, Yaling; Liang, Xing-Jie; Luo, Yang","year":2025,"journal":"Science translational medicine, 17(830), eadv0313","doi":"10.1126/scitranslmed.adv0313","pmid":"41442500","tags":["antimicrobial-peptides","drug-delivery-systems","inflammation-immunology"],"studyType":"animal-study","evidenceStrength":"low-moderate","keyFinding":"BATMAN peptide nanoparticle simultaneously targets bacteria and rejuvenates immunosuppressed macrophages via tuftsin-FcγR signaling in preclinical sepsis.","whyItMatters":"Sepsis kills millions annually and secondary infections are the leading cause of late sepsis deaths — this dual-action approach addresses both problems.","specificNumbers":"Components: ubiquicidin (bacteria-targeting), cholesteryl hemisuccinate (lipase-sensitive), FFVLK (assembly), tuftsin (immune activation); tested in mouse sepsis model.","methodology":"Self-assembling peptide nanoparticle design with preclinical evaluation in sepsis-associated secondary infection models.","limitations":"Preclinical study — human sepsis is highly heterogeneous and may respond differently. Manufacturing complexity of multi-domain peptide nanoparticles."},{"rthcId":"RPEP-13149","title":"Novel antimicrobial peptide ECCT from Chinese water snake is a potential candidate for the treatment of Helicobacter pylori infection and gastric cancer.","authors":"Qiu, Jie; Shi, Wenzhuang; Qian, Zhenghai; Zhang, Pengyu; Li, Shuangyu; Shen, Genhai; Wang, Yipeng; Li, Bin","year":2025,"journal":"Microbial pathogenesis, 206, 107821","doi":"10.1016/j.micpath.2025.107821","pmid":"40553920","tags":["antimicrobial-peptides","gastrointestinal-effects","inflammation-immunology"],"studyType":"laboratory","evidenceStrength":"low","keyFinding":"Snake-derived ECCT peptide shows both anti-H. pylori activity and anti-gastric cancer properties.","whyItMatters":"H. pylori infects half the world's population and is the primary cause of gastric cancer — new treatment options are urgently needed.","specificNumbers":"MIC determined against multiple pathogens; suppressed proinflammatory cytokine transcription; inhibited MAPK pathway.","methodology":"cDNA cloning, phylogenetic/structural analysis, MIC determination, and anti-H. pylori and anti-cancer testing.","limitations":"In vitro study — bioavailability, stability in gastric acid, and in vivo efficacy need assessment."},{"rthcId":"RPEP-13150","title":"Electroacupuncture of Guanyuan (CV4) Acupoint Improved Pelvic Inflammatory Disease Pain by Inhibiting Neuroinflammation and Sympathetic Activity.","authors":"Qu, Jinyu; Peng, Yingchun; Shen, Xuefang; Xiong, Jin; Wang, Huan; Xiao, Xiang; Wang, Yili","year":2025,"journal":"Immunity, inflammation and disease, 13(11), e70299","doi":"10.1002/iid3.70299","pmid":"41194515","tags":["cgrp-peptides","substance-p-tachykinins","inflammation-immunology"],"studyType":"animal-study","evidenceStrength":"low","keyFinding":"Electroacupuncture at CV4 (2/100 Hz) reduced PID pain by inhibiting sympathetic nerve activity and neurogenic inflammation in rats.","whyItMatters":"Non-pharmaceutical pain management for PID could reduce antibiotic and analgesic overuse while addressing a common gynecological condition.","specificNumbers":"Rat PID model; 2/100 Hz EA at CV4; reduced SP, CGRP, TNF-alpha, IL-2, TGF-beta1, ICAM-1; improved MWT and TWL.","methodology":"Rat PID model with EA at 2, 100, and 2/100 Hz frequencies; pain behavior, histopathology, TH expression, and inflammatory marker assessment.","limitations":"Rat model with small groups (n=6). Translation to human PID pain management needs clinical trials."},{"rthcId":"RPEP-13151","title":"Weight Regain After Liraglutide, Semaglutide or Tirzepatide Interruption: A Narrative Review of Randomized Studies.","authors":"Quarenghi, Massimo; Capelli, Silvia; Galligani, Giulia; Giana, Arianna; Preatoni, Giorgia; Turri Quarenghi, Rosamaria","year":2025,"journal":"Journal of clinical medicine, 14(11)","doi":"10.3390/jcm14113791","pmid":"40507553","tags":["glp-1-receptor-agonists","gip-receptor","obesity-weight-management"],"studyType":"systematic-review","evidenceStrength":"moderate-high","keyFinding":"Weight regain after GLP-1 drug discontinuation is substantial and consistent across randomized trials for liraglutide, semaglutide, and tirzepatide.","whyItMatters":"If weight returns after stopping, patients face a choice between lifelong medication use or accepting weight regain — with major cost and safety implications.","specificNumbers":"Reviews RCTs for liraglutide, semaglutide, and tirzepatide; weight regain of approximately two-thirds of lost weight within 1-2 years post-discontinuation.","methodology":"Narrative review of RCTs from PubMed, Cochrane Library, and Google Scholar published in the last 10 years.","limitations":"Narrative review — does not quantitatively pool results. Limited long-term post-discontinuation data available."},{"rthcId":"RPEP-13152","title":"A preliminary study of the physiological and perceptual effects of GLP-1 receptor agonists during alcohol consumption in people with obesity.","authors":"Quddos, Fatima; Fowler, Mary; de Lima Bovo, Ana Carolina; Elbash, Zacarya; Tegge, Allison N; Gatchalian, Kirstin M; Kablinger, Anita S; DiFeliceantonio, Alexandra G; Bickel, Warren K","year":2025,"journal":"Scientific reports, 15(1), 32385","doi":"10.1038/s41598-025-17927-w","pmid":"41093891","tags":["glp-1-receptor-agonists","clinical-applications"],"studyType":"rct","evidenceStrength":"low-moderate","keyFinding":"Preliminary evidence on physiological and perceptual effects of GLP-1 drugs during alcohol consumption in obese individuals.","whyItMatters":"If GLP-1 drugs can safely reduce alcohol consumption, they could address two major health crises — obesity and alcohol use disorder — simultaneously.","specificNumbers":"N=20 (1:1 allocation); no significant differences in alcohol PK between GLP-1 RA users and controls.","methodology":"Observational study measuring physiological and perceptual outcomes during alcohol consumption in GLP-1 RA users with obesity.","limitations":"Preliminary study — small sample, observational design. Cannot establish causation or compare to established AUD treatments."},{"rthcId":"RPEP-13153","title":"Dopaminergic and Opioid Systems Interact to Produce Peripheral Antinociception in Mice.","authors":"Queiroz, Bárbara F G; Barra, Walace C P; Fonseca, Flávia C S; Irie, Audrey L; Romero, Thiago R L; Duarte, Igor D G","year":2025,"journal":"Journal of integrative neuroscience, 24(10), 44311","doi":"10.31083/JIN44311","pmid":"41200990","tags":["opioid-peptides","neuroprotection-neuroregeneration"],"studyType":"animal-study","evidenceStrength":"low","keyFinding":"Peripheral dopamine and opioid systems interact synergistically to inhibit nociception in mice through local receptor and peptide mechanisms.","whyItMatters":"Peripheral analgesic combinations could provide pain relief without the central side effects (drowsiness, addiction) of systemic opioids.","specificNumbers":"Naloxone, nor-BNI (kappa), and naltrindole (delta) reversed dopamine agonist analgesia; opioid peptide degradation inhibitor enhanced effects.","methodology":"Mouse paw withdrawal test with PGE2-induced hyperalgesia, pharmacological manipulation of dopamine and opioid receptors, ANOVA analysis.","limitations":"Mouse model — human peripheral pain physiology may differ. Acute pain model may not reflect chronic pain conditions."},{"rthcId":"RPEP-13154","title":"Evaluation of gastric content in fasting patient during semaglutide use: an observational study.","authors":"Queiroz, Veronica Neves Fialho; Falsarella, Priscila Mina; Chaves, Renato Carneiro de Freitas; Francisco Neto, Miguel Jose; Silva, João Manoel; Araújo, Guilherme Freitas; Takaoka, Flávio; Pfeilsticker, Flávia Julie do Amaral; Mendes, Guilherme Falleiros; Garcia, Rodrigo Gobbo","year":2025,"journal":"Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery, 21(2), 146-151","doi":"10.1016/j.soard.2024.08.039","pmid":"39343660","tags":["glp-1-receptor-agonists","safety-side-effects","gastrointestinal-effects"],"studyType":"observational","evidenceStrength":"low-moderate","keyFinding":"Semaglutide users had more residual gastric content than controls on ultrasound despite following standard 8-hour fasting protocols.","whyItMatters":"Residual stomach content increases aspiration risk during anesthesia — this has major implications for surgical planning in GLP-1 drug users.","specificNumbers":"N=30 (15 semaglutide, 15 controls); semaglutide within 7 days; 73% vs 7% full stomach after standard fasting; minimum 8-hour solid food fast.","methodology":"Observational cross-sectional study using gastric ultrasonography in 30 fasting volunteers (15 semaglutide users, 15 controls).","limitations":"Small sample (30 total). Single center. Cross-sectional design. Specific semaglutide doses not detailed."},{"rthcId":"RPEP-13155","title":"Usefulness of brain-type natriuretic peptide (BNP) levels in pregnancy.","authors":"Quek, Stuart; Zill-E-Huma, Rabia; Andrews, Mark; Mouyis, Maria","year":2025,"journal":"Obstetric medicine, 1753495X251398074","doi":"10.1177/1753495X251398074","pmid":"41451358","tags":["natriuretic-peptides","biomarkers-diagnostics","cardiovascular-effects"],"studyType":"narrative-review","evidenceStrength":"low-moderate","keyFinding":"BNP/NT-proBNP show promise for cardiac assessment in pregnancy but are limited by physiological elevations and lack of pregnancy-specific reference ranges.","whyItMatters":"Cardiac disease in pregnancy is a leading cause of maternal death — better diagnostic tools could save lives.","specificNumbers":"No specific thresholds established; reviews available literature on BNP/NT-proBNP in pregnancy.","methodology":"Systematic review of Medline, PubMed, Cochrane Register, and Cochrane Database on BNP use in pregnancy.","limitations":"Limited and heterogeneous evidence base. Pregnancy-specific reference ranges remain undefined."},{"rthcId":"RPEP-13156","title":"Can Clinical Biomarkers Guide Optimal Therapeutic Selection in Type 2 Diabetes Mellitus? A Scoping Review.","authors":"Quinaglia, Thiago; Silva, Gustavo L R; Matos-Souza, Jose Roberto; Coelho-Filho, Otavio Rizzi; Nadruz, Wilson; Sposito, Andrei C","year":2025,"journal":"Current atherosclerosis reports, 27(1), 121","doi":"10.1007/s11883-025-01368-x","pmid":"41343130","tags":["natriuretic-peptides","biomarkers-diagnostics","cardiovascular-effects","glp-1-receptor-agonists"],"studyType":"systematic-review","evidenceStrength":"moderate","keyFinding":"Imaging biomarkers (coronary calcium, cardiac/hepatic steatosis) and circulating biomarkers provide superior cardiovascular risk prediction in T2DM compared to traditional risk assessment tools.","whyItMatters":"Personalized treatment selection based on biomarkers could help ensure patients receive the diabetes medications most likely to protect their hearts and kidneys.","specificNumbers":"No specific thresholds proposed; scoping review of imaging, circulating, and body composition biomarkers.","methodology":"Scoping review of published literature on novel biomarkers for cardiovascular and renal risk stratification in type 2 diabetes.","limitations":"Scoping review format provides breadth but not the systematic rigor of a full meta-analysis; many biomarkers still need prospective validation in large clinical trials."},{"rthcId":"RPEP-13157","title":"Efficacy of Liraglutide for Weight Loss in Overweight and Obese Non-diabetic Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.","authors":"Quinapanta Castro, Néstor Israel; Almeida, Mishell; Orbea, Andres F; Andrade, Domenica N; Flores Carrera, Jonathan; Yepez Vargas, Francisco; Carrasco, Mariela L","year":2025,"journal":"Cureus, 17(4), e82479","doi":"10.7759/cureus.82479","pmid":"40385831","tags":["glp-1-receptor-agonists","obesity-weight-management"],"studyType":"meta-analysis","evidenceStrength":"high","keyFinding":"Liraglutide produces statistically and clinically significant weight loss in non-diabetic overweight and obese adults compared to placebo across pooled randomized controlled trials.","whyItMatters":"Confirms that liraglutide's weight loss benefits extend beyond diabetes management, supporting its use as a standalone obesity treatment.","specificNumbers":"Multiple RCTs pooled; significant reductions in body weight and BMI vs placebo; GRADE and Cochrane risk-of-bias assessments included.","methodology":"Systematic review and meta-analysis of randomized controlled trials following PRISMA guidelines, using PubMed/MEDLINE, Scopus, and Web of Science databases with random effects modeling.","limitations":"Limited to published randomized controlled trials; heterogeneity between studies in dosing and duration; long-term weight maintenance data beyond trial periods not assessed."},{"rthcId":"RPEP-13158","title":"Investigating the Impact of Ashwagandha and Meditation on Stress Induced Obesogenic Eating Behaviours.","authors":"Quinones, Daniel; Barrow, Michelle; Seidler, Karin","year":2025,"journal":"Journal of the American Nutrition Association, 44(1), 68-88","doi":"10.1080/27697061.2024.2401054","pmid":"39254702","tags":["neuropeptide-y","ghrelin","appetite-metabolism"],"studyType":"systematic-review","evidenceStrength":"low-moderate","keyFinding":"Both ashwagandha and meditation show potential to reduce cortisol levels and modulate stress-related appetite pathways including neuropeptide Y, ghrelin, and dopaminergic signaling.","whyItMatters":"Addressing the hormonal root cause of stress eating — rather than just willpower — could provide more sustainable approaches to obesity prevention.","specificNumbers":"12 searches, 330 hits, 51 studies met inclusion criteria; covers HPA axis, NPY, ghrelin, leptin, insulin, and dopamine pathways.","methodology":"Systematic search of the literature with critical appraisal; 12 searches yielding 330 hits, evaluating ashwagandha, meditation, and mindfulness in relation to stress response mechanisms.","limitations":"Literature review rather than original clinical trial; heterogeneous study designs across reviewed papers; ashwagandha dosing and meditation protocols vary widely."},{"rthcId":"RPEP-13159","title":"Repurposing Diabetes Therapies in CKD: Mechanistic Insights, Clinical Outcomes and Safety of SGLT2i and GLP-1 RAs.","authors":"Rabbani, Syed Arman; El-Tanani, Mohamed; Kumar, Rakesh; Saini, Manita; El-Tanani, Yahia; Sharma, Shrestha; Aljabali, Alaa A A; Hajeer, Eman; Rizzo, Manfredi","year":2025,"journal":"Pharmaceuticals (Basel, Switzerland), 18(8)","doi":"10.3390/ph18081130","pmid":"40872522","tags":["glp-1-receptor-agonists","sglt2-inhibitors","kidney-function"],"studyType":"narrative-review","evidenceStrength":"moderate-high","keyFinding":"SGLT2 inhibitors protect kidneys by restoring tubuloglomerular feedback and reducing renal injury, while GLP-1 RAs reduce oxidative stress and inflammation — both offering organ protection beyond glycemic control.","whyItMatters":"Demonstrates that these diabetes drugs should be considered essential kidney and heart medications, not just blood sugar treatments, for CKD patients.","specificNumbers":"Reviews multiple landmark trials (CREDENCE, DAPA-CKD, EMPA-KIDNEY, FLOW); summarizes mechanisms and outcomes.","methodology":"Narrative review summarizing clinical trials and mechanistic studies evaluating SGLT2i and GLP-1 RA effects on kidney function, cardiovascular outcomes, and disease progression in CKD/DKD.","limitations":"Narrative review format lacks the systematic rigor of meta-analysis; long-term outcomes data still accumulating for some populations; not all CKD stages equally studied."},{"rthcId":"RPEP-13160","title":"Effect of kisspeptin, neurokinin, and dynorphin neurons on regulation of reproduction.","authors":"Racková, Jana","year":2025,"journal":"Ceska gynekologie, 90(5), 413-417","doi":"10.48095/cccg2025413","pmid":"41170798","tags":["kisspeptin","neurokinin-b","opioid-peptides"],"studyType":"narrative-review","evidenceStrength":"moderate","keyFinding":"KNDy neurons integrate hormonal feedback (estrogen, progesterone, testosterone) and environmental cues to control GnRH pulse frequency and amplitude, making them central regulators of reproductive function.","whyItMatters":"Understanding KNDy neurons opens the door to targeted therapies for infertility, PCOS, endometriosis, and other reproductive disorders by modulating specific neuropeptide pathways.","specificNumbers":"No specific clinical data; reviews molecular mechanisms of kisspeptin, neurokinin B, and dynorphin in reproduction.","methodology":"Narrative review of published literature on KNDy neuron biology and their role in reproductive regulation.","limitations":"Much of the detailed KNDy neuron physiology comes from animal models; human clinical data on KNDy-targeted therapies is still emerging."},{"rthcId":"RPEP-13161","title":"Critical discourse analysis of social media advertisements for GLP-1 receptor agonist weight loss drugs: implications for public perceptions and health communication.","authors":"Rad, J; Melendez-Torres, G J","year":2025,"journal":"BMC public health, 25(1), 2996","doi":"10.1186/s12889-025-24197-8","pmid":"40890660","tags":["glp-1-receptor-agonists","obesity-weight-management"],"studyType":"qualitative","evidenceStrength":"low","keyFinding":"GLP-1 RA weight loss drug ads on social media employ specific discursive strategies that frame these medications in ways that shape public expectations and consumer decision-making.","whyItMatters":"Understanding how pharmaceutical advertising influences public perception is crucial as GLP-1 medications become mainstream, affecting patient expectations, medication adherence, and healthcare utilization.","specificNumbers":"90 ads analyzed from Facebook/Instagram (Feb 2023-Feb 2024); 4 key themes identified; Fairclough CDA model applied.","methodology":"Critical discourse analysis (CDA) of Facebook and Instagram advertisements for GLP-1 RA weight loss drugs collected via keyword searches from February 2023 to February 2024, with thematic analysis of recurring patterns.","limitations":"Limited to Facebook and Instagram only; collection period may not capture evolving ad strategies; CDA is inherently interpretive; does not measure actual impact on consumer behavior."},{"rthcId":"RPEP-13162","title":"The Potential of the Peptide Drug Semax and Its Derivative for Correcting Pathological Impairments in the Animal Model of Alzheimer's Disease.","authors":"Radchenko, A I; Kuzubova, E V; Apostol, A A; Mitkevich, V A; Andreeva, L A; Limborska, S A; Stepenko, Yu V; Shmigerova, V S; Solin, A V; Korokin, M V; Pokrovskii, M V; Myasoedov, N F; Makarov, A A","year":2025,"journal":"Acta naturae, 17(4), 110-120","doi":"10.32607/actanaturae.27808","pmid":"41479572","tags":["bioactive-peptides","neuroprotection-neuroregeneration"],"studyType":"animal-study","evidenceStrength":"low-moderate","keyFinding":"Semax and its derivative improved behavioral performance and reduced amyloidosis in transgenic Alzheimer's mice, suggesting neuroprotective potential.","whyItMatters":"Safe, effective Alzheimer's treatments remain elusive; natural neuroprotective peptides like Semax could offer therapeutic benefits without the significant side effects seen in antibody-based amyloid therapies.","specificNumbers":"APPswe/PS1dE9/Blg transgenic mice; improved performance in open field, novel object recognition, and Barnes maze tests; reduced amyloidosis.","methodology":"Preclinical study in transgenic APPswe/PS1dE9/Blg mice using open field, novel object recognition, and amyloid pathology assessment.","limitations":"Mouse model study — results may not translate directly to human Alzheimer's; specific dosing, treatment duration, and long-term effects need further investigation."},{"rthcId":"RPEP-13163","title":"Regional trends and disparities in newer GLP1 receptor agonist initiation among real-world adult patients eligible for obesity treatment.","authors":"Radwan, Rotana M; Lee, Yao An; Kotecha, Pareeta; Wright, Davene R; Hernandez, Inmaculada; Ramon, Ronald; Donahoo, William T; Chen, Yong; Allen, John M; Bian, Jiang; Guo, Jingchuan","year":2025,"journal":"Diabetes, obesity & metabolism, 27(6), 3113-3123","doi":"10.1111/dom.16318","pmid":"40035205","tags":["glp-1-receptor-agonists","obesity-weight-management","clinical-applications"],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"Only 1.8% of 319,949 eligible adults initiated newer GLP-1 RA anti-obesity medications, with significant sociodemographic and clinical disparities in who starts treatment.","whyItMatters":"The enormous gap between eligibility and actual medication use suggests major access barriers — cost, insurance, provider awareness, and systemic inequities — that must be addressed for GLP-1 medications to achieve their public health potential.","specificNumbers":"N=319,949 eligible adults; 1.8% initiated GLP-1 RAs; semaglutide 77.9%, tirzepatide 19.7%, liraglutide 17.8%.","methodology":"Retrospective cohort study using OneFlorida+ electronic health records (2015-2024) with multivariable logistic regression to identify factors associated with GLP-1 RA initiation.","limitations":"Single regional health network (Florida); EHR data may miss prescriptions filled outside the network; cannot distinguish between patient choice and provider/system barriers."},{"rthcId":"RPEP-13164","title":"Trends and Disparities in Newer GLP1 Receptor Agonist Initiation among Real-World Adult Patients Eligible for Obesity Treatment.","authors":"Radwan, Rotana M; Lee, Yao An; Kotecha, Pareeta; Wright, Davene R; Hernandez, Inmaculada; Ramon, Ronald; Donahoo, William T; Chen, Yong; Allen, John M; Bian, Jiang; Guo, Jingchuan","year":2025,"journal":"medRxiv : the preprint server for health sciences","doi":"10.1101/2025.01.20.25320839","pmid":"39974110","tags":["glp-1-receptor-agonists","obesity-weight-management","clinical-applications"],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"Same as published version: only 1.8% of 319,949 eligible adults initiated GLP-1 RA anti-obesity medications, with significant racial, socioeconomic, and geographic disparities.","whyItMatters":"Preprint made these important access disparity findings available to the research community months before formal publication, accelerating awareness of the GLP-1 access gap.","specificNumbers":"N=319,949; 1.8% initiation rate; semaglutide 77.9%; same data as published version.","methodology":"Retrospective cohort study using OneFlorida+ EHR data (2015-2024) with multivariable logistic regression — preprint version of peer-reviewed publication.","limitations":"Preprint — not yet peer-reviewed at time of posting; same methodological limitations as the published version (single regional network, EHR data constraints)."},{"rthcId":"RPEP-13165","title":"The Role of GLP-1 Analogues in the Treatment of Obesity-Related Asthma Phenotype.","authors":"Radzik-Zając, Joanna","year":2025,"journal":"Biomedicines, 13(11)","doi":"10.3390/biomedicines13112610","pmid":"41301704","tags":["glp-1-receptor-agonists","inflammation-immunology","clinical-applications"],"studyType":"narrative-review","evidenceStrength":"low-moderate","keyFinding":"GLP-1 receptor agonists show potential as an innovative treatment for obesity-related asthma through anti-inflammatory, immunomodulatory, and weight-reduction mechanisms.","whyItMatters":"Obesity-related asthma is notoriously difficult to treat with standard medications; GLP-1 RAs could address the root metabolic causes rather than just symptoms.","specificNumbers":"No specific trial data for asthma outcomes; reviews mechanistic evidence and observational signals.","methodology":"Literature review examining the pathophysiology of obesity-related asthma and the potential therapeutic role of GLP-1 receptor agonists.","limitations":"Review article without original clinical data; dedicated clinical trials of GLP-1 RAs specifically for obesity-related asthma outcomes are still needed."},{"rthcId":"RPEP-13166","title":"Heart failure with preserved ejection fraction therapeutics: in search of the pillars.","authors":"Rafei, Abdelghani El; Harrington, Josephine A; Tavares, Caio A M; Guimarães, Patrícia O; Ambrosy, Andrew P; Bonaca, Marc P; Sauer, Andrew J; Vardeny, Orly; Canonico, Mario Enrico","year":2025,"journal":"Heart failure reviews, 30(5), 1005-1014","doi":"10.1007/s10741-025-10524-z","pmid":"40399553","tags":["glp-1-receptor-agonists","sglt2-inhibitors","cardiovascular-effects"],"studyType":"narrative-review","evidenceStrength":"moderate-high","keyFinding":"SGLT2 inhibitors, non-steroidal MRAs, and GLP-1 receptor agonists have demonstrated benefits in landmark HFpEF trials, establishing the first effective treatment paradigm for this condition.","whyItMatters":"HFpEF has been called cardiology's \"biggest unmet need\" for decades; these new drug classes finally offer patients disease-modifying treatment options.","specificNumbers":"~8 million HF patients in US; ~50% have HFpEF; <25% survive beyond 5 years; reviews STEP-HFpEF, SUMMIT, and other landmark trials.","methodology":"Review of landmark clinical trials and emerging evidence for novel therapeutic classes in HFpEF.","limitations":"Review article; individual trial populations and inclusion criteria differ; long-term outcomes and optimal combination strategies still being studied."},{"rthcId":"RPEP-13167","title":"Impact of Erenumab on Comorbid Depression, Anxiety, and Sleep Quality in Migraine: A Registry for Migraine (REFORM) Study.","authors":"Raffaelli, Bianca; Thuraiaiyah, Janu; Christensen, Rune Häckert; Al-Khazali, Haidar M; Ashina, Håkan; Snellman, Josefin; Maio-Twofoot, Tina; Ashina, Messoud","year":2025,"journal":"European journal of neurology, 32(11), e70402","doi":"10.1111/ene.70402","pmid":"41201210","tags":["cgrp-peptides","migraine-headache","clinical-applications"],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"Erenumab 140 mg monthly for 24 weeks improved depression, anxiety (HADS scores), and sleep quality (PSQI scores) in addition to reducing migraine frequency.","whyItMatters":"Demonstrating that CGRP-targeted therapy improves psychiatric comorbidities suggests these symptoms may be partly driven by the same CGRP pathways, and that treating migraine effectively has broader mental health benefits.","specificNumbers":"140 mg erenumab monthly for 24 weeks; outcomes assessed at weeks 12 and 24 using HADS and PSQI; responders (>=50% migraine reduction) had greater psychiatric improvement.","methodology":"Non-randomized, single-arm, open-label trial within the prospective Registry for Migraine (REFORM); 140 mg erenumab monthly for 24 weeks with assessments at baseline, week 12, and week 24.","limitations":"Open-label, single-arm design without placebo control; improvements could partly reflect reduced migraine burden rather than direct psychiatric effects; registry-based recruitment may introduce selection bias."},{"rthcId":"RPEP-13168","title":"The Expanding Role of HLA-E in Host Defense: A Target for Broadly Applicable Vaccines and Immunotherapies.","authors":"Rafieiyan, Mahsa; La Manna, Marco Pio; Dieli, Francesco; Caccamo, Nadia; Badami, Giusto Davide","year":2025,"journal":"Cells, 14(24)","doi":"10.3390/cells14241983","pmid":"41440003","tags":["bioactive-peptides","inflammation-immunology","drug-delivery-systems"],"studyType":"narrative-review","evidenceStrength":"moderate","keyFinding":"HLA-E can present pathogen-derived peptides to CD8+ T cells, eliciting cytotoxic immune responses, and its minimal polymorphism makes it an ideal target for universally applicable vaccines and immunotherapies.","whyItMatters":"Universal immune targets like HLA-E could solve the fundamental challenge of HLA diversity that limits current vaccine and immunotherapy effectiveness across populations.","specificNumbers":"No specific clinical data; reviews immunological mechanisms and emerging therapeutic platforms.","methodology":"Review of published literature on HLA-E biology, HLA-E-restricted T cell responses in infections, and therapeutic applications in vaccine and immunotherapy development.","limitations":"Much HLA-E research is still preclinical; the breadth of pathogen peptides presented by HLA-E and the strength of resulting immune responses need further characterization."},{"rthcId":"RPEP-13169","title":"Rationale Design of a Zn(II)-Coordinated, Cell Penetrating, and Functionalized Tetrapeptide Self-Assembly for Delivery of Chemotherapeutic Drugs to Folic Acid Receptor-Expressing Cancer Cells.","authors":"Raghul, Nanjundan; Lye, Anushree; Goswami, Bhagwat Giri; Nayak, Suman; Stewart, Adele; Lo, Rabindranath; Maity, Biswanath; Das, Priyadip","year":2025,"journal":"ACS applied bio materials, 8(8), 7270-7283","doi":"10.1021/acsabm.5c00965","pmid":"40734540","tags":["peptide-chemistry-design","drug-delivery-systems","cancer-oncology"],"studyType":"laboratory","evidenceStrength":"low","keyFinding":"Zinc-coordinated tetrapeptide PB1 (with Trp-Trp sequence) self-assembles into nanostructures that, when functionalized with folic acid, selectively deliver chemotherapy to folic acid receptor-expressing cancer cells.","whyItMatters":"Short peptide-based drug delivery systems combine biocompatibility, ease of manufacturing, and chemical versatility — potentially offering safer and more targeted cancer chemotherapy.","specificNumbers":"Two tetrapeptides (BOC-YWWD and BOC-WYWD); Zn(II) coordination; folic acid receptor targeting; selective cytotoxicity in FR-positive cells.","methodology":"Rational peptide design with density functional theory (DFT) computational modeling, synthesis of two tetrapeptides, zinc coordination characterization, self-assembly studies, and cancer cell targeting validation.","limitations":"In vitro study — in vivo efficacy, pharmacokinetics, and safety in animal models not yet demonstrated; long-term stability of zinc-peptide assemblies needs assessment."},{"rthcId":"RPEP-13170","title":"The Potential Role of Glucagon-Like Peptide-1 (GLP-1) Agonists for Polycystic Ovary Syndrome.","authors":"Rahim, Shaima; Pergolizzi, Joseph","year":2025,"journal":"Cureus, 17(1), e77998","doi":"10.7759/cureus.77998","pmid":"40007927","tags":["glp-1-receptor-agonists","clinical-applications"],"studyType":"narrative-review","evidenceStrength":"low-moderate","keyFinding":"GLP-1 receptor agonists produce meaningful weight loss and metabolic improvements in PCOS patients, but serious adverse event concerns warrant further long-term safety investigation.","whyItMatters":"PCOS affects up to 10% of reproductive-age women, and obesity-driven insulin resistance is central to its pathology — making GLP-1 RAs a logical but understudied treatment option.","specificNumbers":"No specific trial results detailed in abstract; reviews clinical trial outcomes involving GLP-1 RAs in PCOS.","methodology":"Narrative review examining PCOS diagnostic criteria, current treatments, and clinical trial outcomes involving GLP-1 receptor agonists.","limitations":"Narrative review; most GLP-1 RA trials in PCOS are small and short-term; long-term reproductive and safety outcomes in this specific population are unknown."},{"rthcId":"RPEP-13171","title":"Hecate-FSHβ33-53C/S lytic peptide conjugate selectively kills targeted follicle stimulating hormone receptor (FSHR)-positive cancer cells.","authors":"Rahman, Nafis A; Chrusciel, Marcin; Ponikwicka-Tyszko, Donata; Pulawska-Moon, Kamila; Stelmaszewska, Joanna; Doroszko, Milena; Kreuzer, Oliver J; Rivero-Muller, Adolfo; Li, Xiangdong; Ziecik, Adam J; Wolczynski, Slawomir; Huhtaniemi, Ilpo","year":2025,"journal":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 186, 118022","doi":"10.1016/j.biopha.2025.118022","pmid":"40199133","tags":["peptide-chemistry-design","cancer-oncology"],"studyType":"laboratory","evidenceStrength":"low","keyFinding":"Hecate-FSH beta 33-53 C/S conjugate selectively killed FSHR-positive cancer cells (KGN granulosa tumor cells and FSHR-transfected HEK293 cells) while showing minimal toxicity to FSHR-negative controls.","whyItMatters":"Selective cancer cell killing without harming normal tissue is the holy grail of cancer therapy; this peptide conjugate achieves receptor-targeted cytotoxicity using a nature-derived lytic peptide.","specificNumbers":"Tested in KGN granulosa tumor cells, HEK293-FSHR cells, and FSHR-negative controls; C/S variant showed highest specific cytotoxicity.","methodology":"In vitro cytotoxicity testing of Hecate-FSH beta conjugate variants in FSHR-positive (KGN, HEK293-FSHR) and FSHR-negative (mock-transfected HEK293) cell lines.","limitations":"In vitro study only — in vivo tumor targeting, biodistribution, stability, and safety not yet assessed; FSHR expression varies across tumor types and patients."},{"rthcId":"RPEP-13172","title":"Comparing the impact of systemic pituitary adenylate-cyclase-activating polypeptide (PACAP) and calcitonin gene-related peptide (CGRP) on motion-induced nausea and balance behaviors in mice.","authors":"Rahman, Shafaqat M; Dweh, Abigail; Luebke, Anne E","year":2025,"journal":"PloS one, 20(11), e0334444","doi":"10.1371/journal.pone.0334444","pmid":"41252396","tags":["cgrp-peptides","vip-related-peptides","migraine-headache"],"studyType":"animal-study","evidenceStrength":"low-moderate","keyFinding":"IP PACAP-38 significantly disrupted motion-induced thermoregulation (nausea proxy) in both sexes, increased postural sway in females, and caused balance deficits — comparable to known CGRP effects.","whyItMatters":"Understanding how PACAP affects vestibular function supports developing anti-PACAP therapies for migraine patients who experience significant nausea, dizziness, and balance problems.","specificNumbers":"IP injection of PACAP-38 and CGRP in C57BL/6J mice; PACAP blunted tail vasodilation, increased postural sway (females), impaired balance beam; CGRP affected rotarod.","methodology":"Preclinical study in C57BL/6J mice using IP injection of PACAP-38 and CGRP with motion-induced thermoregulation, center of pressure, rotarod, and balance beam behavioral assays.","limitations":"Mouse model — vestibular and nausea responses may differ in humans; IP delivery may not reflect natural PACAP release patterns during migraine; behavioral proxies for nausea have inherent limitations."},{"rthcId":"RPEP-13173","title":"Systemic calcitonin gene-related peptide modifies auditory and vestibular end organ electrical potentials, and increases sensory hypersensitivities.","authors":"Rahman, Shafaqat M; Faucher, Stefanie; Jonnala, Raajan; Holt, Joseph C; Lee, Choongheon; Luebke, Anne E","year":2025,"journal":"Journal of neurophysiology, 134(1), 107-117","doi":"10.1152/jn.00226.2024","pmid":"40423828","tags":["cgrp-peptides","migraine-headache"],"studyType":"animal-study","evidenceStrength":"low-moderate","keyFinding":"Systemic CGRP modifies electrical potentials in both cochlear and vestibular end organs and increases auditory and vestibular sensory hypersensitivities.","whyItMatters":"Reveals a peripheral mechanism for migraine-associated sensory symptoms, suggesting anti-CGRP drugs may work partly by protecting the inner ear from CGRP-driven hypersensitivity.","specificNumbers":"Systemic CGRP modified cochlear and vestibular end organ potentials; increased auditory and vestibular behavioral sensitivities.","methodology":"Neurophysiology study measuring auditory and vestibular end organ electrical potentials after systemic CGRP administration, with parallel assessment of sensory sensitivity changes.","limitations":"Animal study — human inner ear physiology may respond differently; systemic CGRP delivery may not perfectly mimic natural release patterns during migraine; acute study design."},{"rthcId":"RPEP-13174","title":"GLP-1 Receptor Agonists in Heart Failure.","authors":"Rahmani, Ali Reza; Dhaliwal, Simrat Kaur; Pastena, Paola; Kazakov, Eliot; Jayaseelan, Keerthana; Kalogeropoulos, Andreas","year":2025,"journal":"Biomolecules, 15(10)","doi":"10.3390/biom15101403","pmid":"41154632","tags":["glp-1-receptor-agonists","cardiovascular-effects","natriuretic-peptides"],"studyType":"narrative-review","evidenceStrength":"moderate-high","keyFinding":"GLP-1 RAs benefit heart failure through multiple pathways: sympathetic nervous system modulation, anti-inflammatory signaling, oxidative stress protection, calcium handling improvement, natriuresis, and metabolic optimization.","whyItMatters":"Heart failure remains a leading cause of death; understanding the multiple mechanisms through which GLP-1 RAs help could optimize treatment strategies and identify which patients benefit most.","specificNumbers":"Reviews STEP-HFpEF and SUMMIT trials; covers 6+ mechanistic pathways; ~8 million HF patients in US.","methodology":"Review of clinical trial evidence (STEP-HFpEF, SUMMIT, and others) and mechanistic studies on GLP-1 RA pathways relevant to heart failure pathophysiology.","limitations":"Review article; most strong evidence is for HFpEF with obesity — benefits in other heart failure subtypes less established; long-term heart failure outcomes still being studied."},{"rthcId":"RPEP-13175","title":"Targeted delivery of curcumin and CM11 peptide against hepatocellular carcinoma cells based on binding affinity of PreS1-coated chitosan nanoparticles to SB3 protein.","authors":"Rahmani, Danial; Taheri, Ramezan Ali; Moosazadeh Moghaddam, Mehrdad","year":2025,"journal":"Amino acids, 57(1), 12","doi":"10.1007/s00726-024-03438-x","pmid":"39862295","tags":["antimicrobial-peptides","drug-delivery-systems","cancer-oncology"],"studyType":"laboratory","evidenceStrength":"low","keyFinding":"Chitosan nanoparticles coated with PreS1 peptide delivered curcumin and CM11 antimicrobial peptide selectively to hepatocellular carcinoma cells, showing enhanced cell killing when both drugs were combined.","whyItMatters":"Liver cancer is hard to treat. Using a peptide that recognizes liver cancer markers to guide drug delivery could improve treatment precision.","specificNumbers":"Nanoparticles ~132 nm; PreS1-targeted; dual loading of curcumin and CM11; enhanced cytotoxicity against HepG2 cells.","methodology":"Nanoparticle synthesis and characterization (SEM, DLS), drug loading, PreS1 conjugation, and in vitro cytotoxicity in HepG2 cells.","limitations":"In vitro only. No animal testing. PreS1 targeting assumes SB3 expression, which varies. Stability in blood not tested."},{"rthcId":"RPEP-13176","title":"Cardiorenal Safety Markers With Injectable Glucagon-Like Peptide-1 (GLP-1) Agonists in Type 2 Diabetes: A Network Meta-Analysis.","authors":"Rai, Abigail; Kolli, Mahesh; Singh, Gaurav Pratap; Rishu; Li Cai, Chao Yuan; Balaji, Hariharasudhan; Pongen, Bendangjungla; Joy, Sandra; Sai A K, Shahid","year":2025,"journal":"Cureus, 17(11), e96162","doi":"10.7759/cureus.96162","pmid":"41367446","tags":["glp-1-receptor-agonists","cardiovascular-effects","kidney-function"],"studyType":"meta-analysis","evidenceStrength":"high","keyFinding":"This network meta-analysis ranked injectable GLP-1 RAs for both cardiovascular and kidney outcomes in type 2 diabetes, allowing head-to-head comparisons that individual trials cannot provide.","whyItMatters":"Doctors need to know which GLP-1 drug is best for heart and kidney protection. Network meta-analysis fills the gap left by the absence of direct comparison trials.","specificNumbers":"Network meta-analysis of RCTs; co-primary endpoints: MACE and renal composite outcomes; searched through January 2024.","methodology":"Systematic review and network meta-analysis following standard NMA methods. Multiple databases searched through January 2024.","limitations":"Indirect comparisons carry more uncertainty than direct trials. Different trial populations and designs may affect rankings. Publication bias possible."},{"rthcId":"RPEP-13177","title":"Outcomes of GLP-1 receptor agonist use following ischemic stroke: a propensity score-matched real-world analysis.","authors":"Rai, Pranjal; Bathla, Girish; Praveen, Niharika; Gopikonda, Shreya Sri; Chen, Huanwen Alvin; Salim, Hamza A; Azzam, Ahmed; Essibayi, Muhammed Amir; Altschul, David J; Dmytriw, Adam A; Yedavalli, Vivek S; Latifi, Shahrzad; Malhotra, Ajay; Colasurdo, Marco; Gandhi, Dheeraj; Lakhani, Dhairya A","year":2025,"journal":"Journal of neurology, 272(11), 716","doi":"10.1007/s00415-025-13470-w","pmid":"41118000","tags":["glp-1-receptor-agonists","cardiovascular-effects","clinical-applications"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Stroke patients who started GLP-1 RAs within 6 months of IV thrombolysis had fewer ED visits, hospitalizations, and lower 5-year all-cause mortality compared to matched controls.","whyItMatters":"GLP-1 drugs prevent first strokes in high-risk patients. This study suggests they may also improve outcomes after a stroke has already occurred.","specificNumbers":"TriNetX database; adults >=18 with AIS + IVT; GLP-1 RA within 6 months; 5-year outcomes; reduced ED visits, hospitalizations, and all-cause mortality.","methodology":"Retrospective propensity score matched cohort study using TriNetX platform.","limitations":"Retrospective observational study. Selection bias (healthier patients may get GLP-1 drugs). Cannot prove causation. US data only."},{"rthcId":"RPEP-13178","title":"Discovery of MKP10241, a Novel Small Molecule Targeting the GPR119/Incretin Axis to Treat Metabolic Disorders.","authors":"Rai, Santosh Kumar; Patil, Rakesh Ishwar; Ali, Sazid; Kumar, Rakesh; Khan, Mohd Imran; Panwar, Amit; Reddy, Srinivasa; Ahsan, Muneeb; Iyer, Sunil; Kumar, Anil","year":2025,"journal":"Journal of medicinal chemistry, 68(22), 23781-23800","doi":"10.1021/acs.jmedchem.5c00540","pmid":"41054342","tags":["glp-1-receptor-agonists","gip-receptor","obesity-weight-management"],"studyType":"laboratory","evidenceStrength":"low-moderate","keyFinding":"MKP10241, a novel GPR119 agonist, reduced blood glucose, HbA1c, body weight, and liver fat in diabetic and obese mouse models, and resolved MASH in a specialized liver disease model.","whyItMatters":"GPR119 activation stimulates incretin release (GLP-1 and GIP). A drug targeting this receptor could indirectly activate GLP-1 pathways while also addressing liver disease.","specificNumbers":"Elevated cAMP in GPR119 cells; reduced blood glucose and HbA1c in diabetic mice; reduced body weight and lipids in DIO mice; resolved MASH in STAM model; safe in rat and dog toxicity studies.","methodology":"In vitro receptor activation assays, acute and chronic mouse models (diabetic, DIO, STAM), and preclinical toxicology in rats and dogs.","limitations":"Preclinical only. Mouse models may not predict human response. No human PK or efficacy data. GPR119 agonists have historically had mixed results in clinical trials."},{"rthcId":"RPEP-13179","title":"Analysis of Reporting Trends of Serious Adverse Events Associated With Anti-Obesity Drugs.","authors":"Raičević, Branislava B; Belančić, Andrej; Mirković, Nikola; Janković, Slobodan M","year":2025,"journal":"Pharmacology research & perspectives, 13(2), e70080","doi":"10.1002/prp2.70080","pmid":"39995024","tags":["glp-1-receptor-agonists","safety-side-effects","obesity-weight-management"],"studyType":"pharmacovigilance","evidenceStrength":"low-moderate","keyFinding":"Analysis of European adverse event reporting trends for six anti-obesity drugs revealed clear differences in serious adverse event patterns, with distinct joinpoint trends for each medication.","whyItMatters":"As GLP-1 drug use for obesity surges, monitoring serious side effect trends helps identify emerging safety signals.","specificNumbers":"Six anti-obesity drugs analyzed; EudraVigilance data; Joinpoint Trend Analysis Software; distinct trend patterns identified.","methodology":"Secondary analysis of EudraVigilance adverse event data using Joinpoint regression to identify trend changes.","limitations":"Spontaneous reporting data has inherent biases (under-reporting, stimulated reporting, Weber effect). Cannot determine causation. Reporting rates may reflect media coverage."},{"rthcId":"RPEP-13180","title":"Multicenter, Retrospective, observational study to evaluate the real-world use and effectiveness of a fixed-ratio combination of insulin degludec/liraglutide (IDegLira) in the Pakistani population with Type-2 diabetes (T2D).","authors":"Raja, Umar Yousaf; Wahab, Muhammad Umar; Randhawa, Fawad Ahmed; Hussain, Arshad; Raza, Abbas; Mahar, Saeed Ahmed; Ishtiaq, Osama; Rehman, Tejhmal; Qureshi, Faisal Masood; Ahmed, Ibrar","year":2025,"journal":"Pakistan journal of medical sciences, 41(5), 1494-1498","doi":"10.12669/pjms.41.5.11002","pmid":"40469149","tags":["glp-1-receptor-agonists","insulin-peptides","clinical-applications"],"studyType":"observational","evidenceStrength":"low-moderate","keyFinding":"In 183 Pakistani patients with type 2 diabetes, 6 months of IDegLira (insulin degludec/liraglutide combination) reduced HbA1c by 1.1%, body weight by 1.2 kg, and fasting glucose significantly.","whyItMatters":"Real-world data from Pakistan confirms IDegLira effectiveness in a population rarely represented in clinical trials.","specificNumbers":"N=183; HbA1c reduction -1.1%; weight loss -1.2 kg; FBG: 164.7 to 134.4 mg/dL; 6-month follow-up.","methodology":"Multicenter retrospective observational study across public and private hospitals in Pakistan (April-September 2022).","limitations":"Retrospective. No control group. Small sample. Short follow-up. Selection bias likely."},{"rthcId":"RPEP-13181","title":"Rethinking strategies for solving thyroid dysfunction at the heart of cardiovascular disease.","authors":"Rajagopalan, Viswanathan; Ojamaa, Kaie; Gerdes, A Martin","year":2025,"journal":"Molecular medicine (Cambridge, Mass.), 32(1)","doi":"10.1186/s10020-025-01351-x","pmid":"41331553","tags":["natriuretic-peptides","biomarkers-diagnostics","cardiovascular-effects"],"studyType":"narrative-review","evidenceStrength":"low-moderate","keyFinding":"Patients with heart failure often have low thyroid hormone levels. BNP could serve as a biomarker linking heart failure stage to thyroid function status, guiding thyroid hormone therapy.","whyItMatters":"Thyroid hormones directly affect heart function. If BNP can track both heart failure severity and thyroid status, it becomes a dual-purpose clinical tool.","specificNumbers":"No specific trial results; reviews relationship between BNP, heart failure stage, and thyroid hormone status.","methodology":"Narrative review of thyroid-cardiac axis, BNP as biomarker, and clinical studies of thyroid hormone therapy in HF.","limitations":"Narrative format. BNP-thyroid correlation hypothesis needs prospective validation. Thyroid hormone therapy in HF remains controversial."},{"rthcId":"RPEP-13182","title":"Toward next-generation BNP/NT-proBNP biosensors: multiplexed detection, biofouling control, and digital health integration.","authors":"Rajendran, Jose Varghese; Elahi, Adnan; Scully, Patricia","year":2025,"journal":"Heart failure reviews, 31(1), 8","doi":"10.1007/s10741-025-10573-4","pmid":"41329346","tags":["natriuretic-peptides","biomarkers-diagnostics"],"studyType":"narrative-review","evidenceStrength":"moderate","keyFinding":"Next-generation BNP/NT-proBNP biosensors achieve femtogram-level detection using fluorescence, SERS, and nanozyme technologies, with smartphone-compatible readouts for point-of-care testing.","whyItMatters":"Current BNP testing requires hospital labs. Portable, ultra-sensitive biosensors could enable heart failure monitoring at home or in primary care.","specificNumbers":"Detection limits at femtogram-to-picogram levels; technologies include FRET, quantum dots, SERS, nanozyme LFA, and ECL; smartphone-compatible designs.","methodology":"Critical review of BNP/NT-proBNP detection technologies published 2020-2025.","limitations":"Most technologies still in research phase. Clinical validation in real patient samples limited. Regulatory approval pathways long. Cost-effectiveness not assessed."},{"rthcId":"RPEP-13183","title":"GLP-1-Mediated Pregnancy and Neonatal Complications in Mice.","authors":"Ramamoorthy, Rajalakshmi; Carden, Arianna K; Hussain, Hussain; Druyan, Brian Z; Chen, Ping Ping; Hajjar, Rima; Fernandez, Carmen; Elumalai, Nila; Rashed, Amirah B; Young, Karen; Speciale, Anna Rosa; West, Emily M; Marbin, Staci; Safro, Bradley; Bishop, Ian J; Jayakumar, Arumugam R; Sanchez-Ramos, Luis; Paidas, Michael J","year":2025,"journal":"Journal of developmental biology, 13(3)","doi":"10.3390/jdb13030029","pmid":"40843897","tags":["glp-1-receptor-agonists","safety-side-effects"],"studyType":"animal-study","evidenceStrength":"low","keyFinding":"High-dose GLP-1 injections during early or late mouse pregnancy caused maternal weight loss, neonatal weight loss, and increased pup mortality. mRNA analysis revealed widespread gene expression changes in neonates.","whyItMatters":"Millions of women of childbearing age use GLP-1 drugs. This mouse study raises concerns about potential fetal and neonatal harm from GLP-1 exposure during pregnancy.","specificNumbers":"A/J mice; rGLP-1 1000 nmol/kg subcutaneous; injected on embryonic day 1 (early) or day 15 (late); maternal and pup weight loss; increased pup mortality; mRNA sequencing of neonatal tissues.","methodology":"Mouse pregnancy model with subcutaneous GLP-1 injection at two time points. Body weight, morphology, mortality tracking, and mRNA sequencing.","limitations":"Very high GLP-1 dose. Mouse reproductive biology differs from human. Single mouse strain (A/J). Small litter sizes likely. Cannot extrapolate directly to therapeutic GLP-1 RA doses."},{"rthcId":"RPEP-13184","title":"Antibiofilm activities of lactoferricin-related Trp- and Arg-rich antimicrobial hexapeptides against pathogenic Staphylococcus aureus and Pseudomonas aeruginosa strains.","authors":"Ramamourthy, Gopal; Vogel, Hans J","year":2025,"journal":"Biochemistry and cell biology = Biochimie et biologie cellulaire, 103, 1-18","doi":"10.1139/bcb-2024-0183","pmid":"39418670","tags":["antimicrobial-peptides","peptide-chemistry-design"],"studyType":"laboratory","evidenceStrength":"low","keyFinding":"Most Trp- and Arg-rich hexapeptides modeled after lactoferricin showed antibiofilm activity against MRSA and Pseudomonas at concentrations well below their bacterial killing threshold.","whyItMatters":"Biofilms protect bacteria from antibiotics and immune attack. Short peptides that disrupt biofilms at low concentrations could be combined with existing antibiotics.","specificNumbers":"23 hexapeptides tested; based on RRWQWR-NH2 from bovine lactoferrin; MBIC and MBEC measured against GFP-expressing PAO1 and MRSA strains.","methodology":"Peptide synthesis, fluorescence-based biofilm inhibition and eradication assays, crystal violet confirmation.","limitations":"In vitro only. No cytotoxicity testing. No animal biofilm models. Short peptides may have limited stability in vivo."},{"rthcId":"RPEP-13185","title":"GLP-1 Receptor Agonists in Orthopaedic Surgery: Implications for Perioperative Care and Outcomes: An Orthopaedic Surgeon's Perspective.","authors":"Ramanathan, Rahul; Lee, Joon Y; Dalton, Jonathan F; Lin, Ryan T; Lee, Isaac; Gonzalez, Christopher; Shaw, Jeremy D; Schroeder, Gregory D; Kepler, Christopher K; Spitnale, Michael; Vaccaro, Alexander R; Gabrielli, Alexandra S; Wawrose, Richard A","year":2025,"journal":"The Journal of bone and joint surgery. American volume, 107(16), 1879-1886","doi":"10.2106/JBJS.24.01287","pmid":"40833394","tags":["glp-1-receptor-agonists","safety-side-effects","clinical-applications"],"studyType":"narrative-review","evidenceStrength":"moderate","keyFinding":"ASA recommends withholding daily GLP-1 drugs on surgery day and weekly formulations for a week before elective orthopedic procedures due to aspiration risk from delayed gastric emptying.","whyItMatters":"More orthopedic patients take GLP-1 drugs for obesity and diabetes. Delayed gastric emptying creates aspiration risk under anesthesia that surgeons must manage.","specificNumbers":"ASA guidelines: withhold daily dose on surgery day; withhold weekly dose 1 week before; full stomach precautions if GI symptoms present.","methodology":"Narrative review summarizing ASA guidelines and evidence for perioperative GLP-1 RA management in orthopedic surgery.","limitations":"Guidelines based on limited evidence. Optimal fasting duration for GLP-1 users not established. Recommendations may change as evidence accumulates."},{"rthcId":"RPEP-13186","title":"Beyond Heart Failure: Role of NT-Pro-BNP in Diabetes Mellitus Patients with Preserved Ejection Fraction.","authors":"Ramaprabha, S S; Alexander, Hariharan; Latha, Josephine; Mohanty, Pradipta Kumar","year":2025,"journal":"EJIFCC, 36(2), 165-170","doi":null,"pmid":"40584989","tags":["natriuretic-peptides","biomarkers-diagnostics","cardiovascular-effects"],"studyType":"observational","evidenceStrength":"low-moderate","keyFinding":"NT-proBNP can detect early left ventricular diastolic dysfunction in diabetic patients who still have normal ejection fraction, before symptoms develop.","whyItMatters":"Many diabetic patients have hidden heart dysfunction. NT-proBNP testing could catch problems before they become symptomatic heart failure.","specificNumbers":"Not detailed in abstract; focuses on NT-proBNP's role in detecting diastolic dysfunction with preserved ejection fraction.","methodology":"Observational study assessing NT-proBNP levels in diabetic patients with preserved ejection fraction.","limitations":"Limited study details in abstract. Likely small sample. NT-proBNP cutoffs for diastolic dysfunction in diabetes not standardized."},{"rthcId":"RPEP-13187","title":"Effects of angiotensin-neprilysin inhibition in women vs men: Insights from PARAGLIDE-HF.","authors":"Rambarat, Paula; Erickson, Tyler; Cyr, Derek; Ward, Jonathan; Hernandez, Adrian; Morrow, David; Starling, Randall; Velazquez, Eric; Zieroth, Shelley; Williamson, Kristin; Solomon, Scott; Mentz, Robert","year":2025,"journal":"American heart journal, 288, 41-51","doi":"10.1016/j.ahj.2025.03.017","pmid":"40174692","tags":["natriuretic-peptides","cardiovascular-effects","clinical-applications"],"studyType":"rct","evidenceStrength":"moderate-high","keyFinding":"In the PARAGLIDE-HF trial, sacubitril/valsartan reduced NT-proBNP more than valsartan alone in patients with decompensated HFpEF. The benefit was consistent across both sexes despite baseline differences.","whyItMatters":"Women make up more than half of HFpEF patients. Confirming that sacubitril/valsartan works equally well in both sexes is important for treatment confidence.","specificNumbers":"242 women (52%) and 224 men (48%); NT-proBNP time-averaged reduction greater with S/V vs valsartan; consistent across sex subgroups.","methodology":"Prespecified sex-stratified subgroup analysis of the PARAGLIDE-HF randomized trial.","limitations":"Subgroup analysis. Short follow-up (8 weeks). NT-proBNP is a surrogate outcome. Trial not powered for sex-specific outcomes."},{"rthcId":"RPEP-13188","title":"Single-cell sequencing uncovers sensory neuron-mediated CGRP signaling as a driver of sarcoma progression.","authors":"Ramesh, Sowmya; Qin, Qizhi; Li, Zhao; Cherief, Masnsen; Zhong, Lingke; Archer, Mary; Xing, Xin; Thottappillil, Neelima; Balaji, Devadutta; Bae, Sam; Gomez-Salazar, Mario; Xu, Mingxin; Zhu, Manyu; Uniyal, Ankit; Chang, Leslie; Mazhar, Khadijah; Mittal, Monisha; Birbrair, Alexander; McCarthy, Edward F; Morris, Carol D; Levi, Benjamin; Guan, Yun; Clemens, Thomas L; Price, Theodore J; James, Aaron W","year":2025,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 122(43), e2500161122","doi":"10.1073/pnas.2500161122","pmid":"41118222","tags":["cgrp-peptides","cancer-oncology","neuroprotection-neuroregeneration"],"studyType":"animal-study","evidenceStrength":"moderate","keyFinding":"Sensory nerve fibers that release CGRP drive osteosarcoma growth, vascularization, and metastasis. Blocking these nerves with TrkA inhibition reduced tumor progression and improved survival in mice.","whyItMatters":"Cancer pain is not just a symptom. The nerves that signal pain actively help bone tumors grow. Blocking CGRP signaling could be both pain relief and cancer treatment.","specificNumbers":"TrkA inhibition in transgenic mice; reduced innervation, vascularization, and metastasis; prolonged survival; single-cell transcriptomics showing reduced CGRP signaling.","methodology":"Chemical-genetic TrkA inhibition in transgenic mice with osteosarcoma. Single-cell RNA sequencing of tumor and microenvironment cells.","limitations":"Mouse osteosarcoma model. Genetic approach may not translate to pharmacological intervention. CGRP role may differ in other cancer types."},{"rthcId":"RPEP-13189","title":"Milk-derived bioactive peptides in insulin resistance and type 2 diabetes.","authors":"Ramezan, Marjan; Arzhang, Pishva; Shin, Andrew C","year":2025,"journal":"The Journal of nutritional biochemistry, 138, 109849","doi":"10.1016/j.jnutbio.2025.109849","pmid":"39870329","tags":["bioactive-peptides","glp-1-receptor-agonists","appetite-metabolism"],"studyType":"narrative-review","evidenceStrength":"low-moderate","keyFinding":"Milk-derived bioactive peptides from casein and whey can improve glycemic control through DPP-IV inhibition, enhanced insulin signaling, and reduced inflammation in preclinical studies.","whyItMatters":"Food-derived peptides that extend GLP-1 activity by blocking DPP-IV could offer a natural, dietary approach to improving insulin resistance.","specificNumbers":"Reviews peptides from casein and whey; mechanisms include DPP-IV inhibition, insulin signaling enhancement, anti-inflammatory effects.","methodology":"Narrative review of in vitro and in vivo studies on milk-derived bioactive peptides and glucose metabolism.","limitations":"Most evidence preclinical. Peptide bioavailability after oral intake unclear. Amounts in regular dairy consumption may be too low for therapeutic effect."},{"rthcId":"RPEP-13190","title":"Visual demonstration of weight loss and health risk improvement with a dual GIP and GLP-1 receptor agonist.","authors":"Ramirez, Sophia; Yang, Ryan; Habibovic, Muhammed; Kennedy, Samantha; Bennett, Jonathan P; Shepherd, John A; Thomas, Diana M; Heymsfield, Steven B","year":2025,"journal":"International journal of obesity (2005), 49(10), 2005-2010","doi":"10.1038/s41366-025-01842-1","pmid":"40659850","tags":["glp-1-receptor-agonists","gip-receptor","obesity-weight-management"],"studyType":"methodology","evidenceStrength":"low","keyFinding":"New visual presentation methods for GLP-1 clinical trial data can convey weight loss and health risk improvement more intuitively than standard graphs and tables.","whyItMatters":"Clinical trial results are hard for patients and non-specialists to understand. Better visual tools could improve informed decision-making.","specificNumbers":"Applied to dual GIP/GLP-1 agonist trial data; demonstrates visual methods for body weight and health risk changes.","methodology":"Development and demonstration of visual presentation methods applied to existing clinical trial data.","limitations":"Methodological demonstration only. Effectiveness not formally tested with patients or clinicians. May oversimplify complex outcomes."},{"rthcId":"RPEP-13191","title":"The cost-effectiveness of subcutaneous semaglutide 2.4 mg in the management of people living with obesity and prediabetes in England.","authors":"Ramos, Mafalda; Larsen, Sara; Fusco, Francesco; Lamotte, Mark; Capehorn, Matthew","year":2025,"journal":"Journal of medical economics, 28(1), 1887-1898","doi":"10.1080/13696998.2025.2575692","pmid":"41090945","tags":["glp-1-receptor-agonists","obesity-weight-management","clinical-applications"],"studyType":"cost-effectiveness","evidenceStrength":"moderate","keyFinding":"Semaglutide 2.4 mg plus diet and exercise reversed prediabetes in 80% of patients (vs 12% with diet alone) and was cost-effective in England when accounting for avoided diabetes progression.","whyItMatters":"Treating prediabetes with semaglutide could prevent millions of diabetes cases, but the drug is expensive. This analysis shows it may still be cost-effective.","specificNumbers":"Based on STEP-10; age 53, BMI 40.1; 80% vs 12% prediabetes reversal at 52 weeks; BMI reduction 13 points greater with semaglutide.","methodology":"Cost-effectiveness analysis using the Core Obesity Model populated with STEP-10 trial data for the English healthcare setting.","limitations":"Model-based with assumptions about long-term outcomes. Based on single trial (STEP-10). Drug costs may change. Real-world adherence may differ from trials."},{"rthcId":"RPEP-13192","title":"GLP-1 Receptor Agonists and Sight-Threatening Ophthalmic Complications in Patients With Type 2 Diabetes.","authors":"Ramsey, David J; Makwana, Bhargav; Dani, Sourbha S; Patel, Manav; Panchal, Krisha; Shah, Jui; Khadke, Sumanth; Kumar, Ashish; Patel, Tirth; Kosiborod, Mikhail N; Fonarow, Gregg C; Ramsey, Kathryn Moynihan; Nohria, Anju; Butler, Javed; Ganatra, Sarju","year":2025,"journal":"JAMA network open, 8(8), e2526321","doi":"10.1001/jamanetworkopen.2025.26321","pmid":"40788647","tags":["glp-1-receptor-agonists","safety-side-effects"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"In a large TriNetX cohort, GLP-1 RA use in type 2 diabetes was associated with increased diabetic retinopathy risk but the study also examined NAION and DR complications.","whyItMatters":"Eye complications are a growing concern with GLP-1 drugs. Large cohort studies help quantify these risks for the millions of patients taking these medications.","specificNumbers":"TriNetX database; adults >=18 with T2D and HbA1c >=6.5%; Jan 2015-Sep 2022; >=2 GLP-1 RA prescriptions as exposure; PSM-adjusted.","methodology":"Retrospective propensity score matched cohort study using TriNetX (published in JAMA Network Open).","limitations":"Observational. Rapid HbA1c reduction may confound retinopathy risk. NAION is rare, limiting statistical power. Cannot determine if risk is drug-related vs mediated by rapid glycemic change."},{"rthcId":"RPEP-13193","title":"GLP-1 receptor agonists and gallbladder disease risk: insights into molecular mechanisms and clinical implications.","authors":"Ramírez-Mejía, Mariana M; Ponciano-Rodriguez, Guadalupe; Eslam, Mohammed; Méndez-Sánchez, Nahum","year":2025,"journal":"Therapeutic advances in endocrinology and metabolism, 16, 20420188251406456","doi":"10.1177/20420188251406456","pmid":"41459016","tags":["glp-1-receptor-agonists","safety-side-effects","gastrointestinal-effects"],"studyType":"narrative-review","evidenceStrength":"moderate","keyFinding":"GLP-1 RAs increase gallstone and gallbladder inflammation risk through suppression of cholecystokinin, altered bile acid composition, and rapid weight loss-related cholesterol supersaturation.","whyItMatters":"Gallbladder problems are one of the most clinically significant side effects of GLP-1 drugs. Understanding the mechanisms could help prevent them.","specificNumbers":"Mechanisms: CCK suppression, bile acid alterations, weight loss-related cholesterol supersaturation; risk increases with dose and duration.","methodology":"Narrative review of molecular mechanisms and clinical evidence for GLP-1 RA-associated biliary disease.","limitations":"Narrative format. Absolute risk increase is modest. Difficult to separate drug effect from rapid weight loss effect. Prevention strategies not well established."},{"rthcId":"RPEP-13194","title":"Chronic cisplatin treatment in young mice induces long-term complications in the peripheral nervous system in a sex-dependent manner.","authors":"Ramírez-Quintanilla, Laura Yanneth; Pérez-Reyes, Santos Adrián; Salazar-Hernández, Martin de Jesus; Torres-Rodríguez, Héctor Fabián; Vargas-Muñoz, Virginia Margarita; García-Araujo, Ana Rebeca; Acosta-González, Rosa Issel; Muñoz-Islas, Enriqueta; Jiménez-Andrade, Juan Miguel","year":2025,"journal":"Neurotoxicology, 111, 103318","doi":"10.1016/j.neuro.2025.103318","pmid":"40930240","tags":["cgrp-peptides","neuroprotection-neuroregeneration"],"studyType":"animal-study","evidenceStrength":"low","keyFinding":"Young mice treated with cisplatin showed lasting nerve damage 4 weeks after treatment, with reduced CGRP+ nerve fiber density in skin and sex-dependent pain responses.","whyItMatters":"Childhood cancer survivors often have lifelong nerve damage from chemotherapy. Understanding CGRP nerve changes could inform pain management strategies.","specificNumbers":"BALB/c mice, 4 weeks old; cisplatin 4 mg/kg IP twice weekly for 4 weeks; assessed 4 weeks post-cessation; reduced CGRP+ and PGP9.5+ fiber density; sex-dependent capsaicin responses.","methodology":"Juvenile mouse cisplatin model. Mechanical withdrawal testing, skin innervation density (CGRP+, PGP9.5+), DRG marker analysis, capsaicin pain testing.","limitations":"Mouse model. Juvenile mouse nerve development differs from human pediatric patients. Single chemotherapy agent. 4-week post-treatment window may not capture full recovery or decline."},{"rthcId":"RPEP-13195","title":"AI-Accelerated Identification of Novel Antimicrobial Peptides for Inhibiting Fusarium graminearum.","authors":"Ran, Yue; Li, Sen; Wang, Ying-Jie; Liang, Jian-Hua; Jiang, Wei; Yu, Ming-Jia","year":2025,"journal":"Journal of agricultural and food chemistry, 73(28), 17471-17482","doi":"10.1021/acs.jafc.5c03429","pmid":"40598766","tags":["antimicrobial-peptides","computational-modeling","peptide-chemistry-design"],"studyType":"computational","evidenceStrength":"low-moderate","keyFinding":"Machine learning identified an antifungal peptide (TP) that nearly completely suppressed Fusarium graminearum at 13.33 uM. Molecular dynamics revealed it works through electrostatic binding followed by hydrophobic insertion.","whyItMatters":"Fusarium blight threatens global wheat production. AI-designed peptides could replace toxic fungicides with biodegradable alternatives.","specificNumbers":"XGBoost model R2=0.77, RMSE=1.8; peptide TP achieved near-complete suppression at 13.33 uM; targets myosin via electrostatic and hydrophobic mechanisms.","methodology":"De novo AMP database construction, physicochemical feature extraction, XGBoost/ML modeling, peptide synthesis, antifungal testing, and molecular dynamics simulations.","limitations":"Lab testing only. Field efficacy unknown. Peptide stability in agricultural settings not tested. Cost of peptide production for agriculture unclear."},{"rthcId":"RPEP-13196","title":"Identification of genes expressed in the pectoral fins and skin of Takifugu rubripes to reveal candidate genes involved in host recognition by the crustacean ectoparasite Caligus fugu.","authors":"Rana, K M Shakil; Matsunaga, Ryohei; Sato, Yoshiki; Suetake, Hiroaki; Kikuchi, Kiyoshi; Ohtsuka, Susumu; Kotani, Tomonari; Tasumi, Satoshi","year":2025,"journal":"Comparative biochemistry and physiology. Part D, Genomics & proteomics, 58, 101731","doi":"10.1016/j.cbd.2025.101731","pmid":"41435496","tags":["bioactive-peptides"],"studyType":"animal-study","evidenceStrength":"low","keyFinding":"RNA-seq of puffer fish fins vs skin identified genes differentially expressed in fins that may serve as chemical cues recognized by parasitic copepods, including neuropeptide-related genes.","whyItMatters":"Understanding how fish parasites find their hosts could improve aquaculture disease management.","specificNumbers":"RNA-seq comparing pectoral fins vs skin of Takifugu rubripes; multiple differentially expressed genes identified.","methodology":"RNA-seq of Takifugu rubripes pectoral fins and skin, differential expression analysis, candidate gene refinement.","limitations":"Fish model with limited peptide relevance to human medicine. Candidate genes not functionally validated. Single fish species."},{"rthcId":"RPEP-13197","title":"Calcitonin Gene-Related Peptide Inhibitor Use in 2018-2023: A Retrospective Cohort Study Across Six Canadian Provinces.","authors":"Randall, Jason R; Martins, Karen; Luu, Huong; Vu, Khanh; Missaoui, Houssem; Fernandez, Smriti; Morrison, Sandy; Stock, David; de Léséleuc, Louis; Liu, Zhaoyu; Manning, Devin; Cheung, Grace; Moura, Cristiano S; Birck, Marina G; Amoozegar, Farnaz; Dutton, Daniel J; Kaboré, Jean-Luc; Bernatsky, Sasha; Klarenbach, Scott W","year":2025,"journal":"The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques, 1-10","doi":"10.1017/cjn.2025.10506","pmid":"41449823","tags":["cgrp-peptides","migraine-headache","clinical-applications"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"CGRP inhibitor use in Canada grew from 11.8 to 57.3 per 100,000 adults between 2018-2023. After starting treatment, patients reduced acute migraine medication use and healthcare utilization.","whyItMatters":"First large-scale population-level data on CGRP inhibitor adoption and real-world impact across multiple Canadian provinces.","specificNumbers":"N=12,851 adults; prevalence grew from 11.8 to 57.3 per 100,000; erenumab use declined as newer agents increased; reduced acute medication and healthcare use post-initiation.","methodology":"Retrospective population-based cohort study using administrative data from six Canadian provinces (2018-2023).","limitations":"Administrative data lacks clinical detail (migraine severity, headache days). Cannot determine which patients benefited most. Provincial formulary differences may affect access."},{"rthcId":"RPEP-13198","title":"Margatoxin Peptide: Preparation and the Potential Use for Biological Applications in Cancer and Neurological Disorders.","authors":"Ranjbari, Faride; Dadkhah, Masoomeh; Pirdel, Zahra; Fathi, Farzaneh","year":2025,"journal":"Protein and peptide letters, 32(11), 791-802","doi":"10.2174/0109298665415268251024053300","pmid":"41486988","tags":["bioactive-peptides","cancer-oncology","neuroprotection-neuroregeneration"],"studyType":"narrative-review","evidenceStrength":"low-moderate","keyFinding":"Margatoxin, a scorpion venom peptide, selectively blocks Kv1.3 potassium channels at picomolar doses and shows promise for cancer and neurological disorders through immune modulation and tumor cell killing.","whyItMatters":"Kv1.3 channels are overexpressed in certain cancers and activated immune cells. A highly selective blocker could be both an immunomodulator and anticancer agent.","specificNumbers":"Active at picomolar concentrations; selective for Kv1.3 channels; good permeability and stability in cancer cells.","methodology":"Narrative review of literature on margatoxin chemistry, pharmacology, and therapeutic potential.","limitations":"Most data preclinical. Venom peptides face challenges in drug development (cost, immunogenicity, delivery). Clinical trials lacking."},{"rthcId":"RPEP-13199","title":"Bionanoconjugates in Neurodegeneration: Peptide-Nanoparticle Alliances for Next-Generation Therapies.","authors":"Ranjitha, V R; Kumar, Anil; Kaalappa, Prashantha","year":2025,"journal":"Pharmaceutical research, 42(12), 2379-2404","doi":"10.1007/s11095-025-03941-0","pmid":"41199078","tags":["peptide-chemistry-design","drug-delivery-systems","neuroprotection-neuroregeneration"],"studyType":"narrative-review","evidenceStrength":"low-moderate","keyFinding":"Peptide-nanoparticle conjugates (like TAT-gold nanoparticles and RGD-polymer systems) overcome peptide drug limitations by improving blood-brain barrier crossing, stability, and targeted delivery for neurodegenerative diseases.","whyItMatters":"Peptide drugs for brain diseases are limited by rapid breakdown and poor brain penetration. Nanoparticle conjugation solves both problems.","specificNumbers":"Peptides <45 amino acids; examples: TAT-functionalized gold NPs, RGD-decorated polymeric systems; improved BBB crossing in preclinical models.","methodology":"Narrative review of bionanoconjugate strategies for neurodegenerative disease therapy.","limitations":"Most evidence preclinical. BBB crossing in humans may differ from animal models. Manufacturing complexity. Regulatory hurdles for nanomedicines."},{"rthcId":"RPEP-13200","title":"GLP-1 agonists are protective against postoperative complications following total knee arthroplasty.","authors":"Ranson, Rachel; Parel, Philip M; Kirkland, Julia; Durbin, Jackson W; Villa, Jordan C; Sterling, Robert","year":2025,"journal":"The Knee, 57, 77-83","doi":"10.1016/j.knee.2025.08.007","pmid":"40834675","tags":["glp-1-receptor-agonists","clinical-applications","muscle-bone-joint"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"Patients taking GLP-1 RAs before total knee replacement had fewer 90-day medical complications than matched controls who did not use these drugs.","whyItMatters":"Many knee replacement patients have obesity and diabetes. GLP-1 drugs might improve surgical outcomes beyond just weight loss.","specificNumbers":"National all-payer claims database; GLP-1 within 6 months pre-TKA; reduced 90-day medical complications; 2-year surgical outcomes analyzed.","methodology":"Retrospective cohort analysis with multivariable regression using national claims data.","limitations":"Claims data lacks clinical detail. Cannot determine if benefits are from weight loss, metabolic improvement, or anti-inflammatory effects. Selection bias possible."},{"rthcId":"RPEP-13201","title":"Cathelicidin-related antimicrobial peptide (CRAMP) is toxic during neonatal murine influenza virus infection.","authors":"Rao, Abhishek S; Ugwu, Nneka; Onufer, Abigail P; Kumova, Ogan; Carey, Alison J","year":2025,"journal":"Journal of immunology (Baltimore, Md. : 1950), 214(5), 1022-1031","doi":"10.1093/jimmun/vkae053","pmid":"40101750","tags":["antimicrobial-peptides","inflammation-immunology"],"studyType":"animal-study","evidenceStrength":"low-moderate","keyFinding":"In neonatal mice with influenza, the cathelicidin antimicrobial peptide CRAMP was harmful rather than protective. Mice lacking CRAMP had better survival after infection.","whyItMatters":"Cathelicidins are usually considered protective. This finding that they can be toxic in neonatal viral infections challenges assumptions about innate immune peptides.","specificNumbers":"3-day-old neonatal mice; CRAMP knockout mice had improved influenza survival; LGG treatment downregulated CRAMP expression.","methodology":"Neonatal mouse influenza model comparing CRAMP-knockout and wild-type mice. LGG probiotic treatment. Transcriptional analysis.","limitations":"Mouse neonatal model. Neonatal mouse immunity differs substantially from human neonatal immunity. Single virus strain tested."},{"rthcId":"RPEP-13202","title":"LL-37 as a biomarker for therapeutic response to scaling and root planing.","authors":"Rao, Karkala Sunanda; Yadalam, Pradeep Kumar; Ravishankar, Potluri Leela; Rajula, Prem Blaisie; Ravikumar, Harshitha; Arunraj, Duraipandian Rex","year":2025,"journal":"Journal of Indian Society of Periodontology, 29(4), 413-417","doi":"10.4103/jisp.jisp_405_24","pmid":"41438788","tags":["antimicrobial-peptides","biomarkers-diagnostics","inflammation-immunology"],"studyType":"observational","evidenceStrength":"low-moderate","keyFinding":"LL-37 gene expression in gum tissue increased after standard periodontal cleaning (scaling and root planing), correlating with clinical improvement in pocket depth and bleeding.","whyItMatters":"LL-37 is a human cathelicidin antimicrobial peptide. Its increase after treatment suggests it helps the gums heal and fight infection.","specificNumbers":"N=30; 17 males, 13 females; aged 30-50; Stage II/III periodontitis; improved PPD, CAL, mSBI at 1 month; increased LL-37 mRNA by qRT-PCR.","methodology":"Observational before-after study. Subgingival tissue sampling at baseline and 1 month post-SRP. qRT-PCR for LL-37.","limitations":"Small sample. No control group. Single time point post-treatment. Cannot determine if LL-37 increase causes or results from improvement."},{"rthcId":"RPEP-13203","title":"Production of Fc-fused receptor agonists for glucagon-like peptide-1/glucose-dependent insulinotropic polypeptide (GLP-1/GIP) in the milk of transgenic mice.","authors":"Rao, Yu; Yu, Shuai; Wang, Bao-Zhu; Cui, Sheng; Gou, Ke-Mian","year":2025,"journal":"Transgenic research, 34(1), 38","doi":"10.1007/s11248-025-00458-5","pmid":"40753531","tags":["glp-1-receptor-agonists","gip-receptor","peptide-chemistry-design"],"studyType":"laboratory","evidenceStrength":"low","keyFinding":"Transgenic mice secreted functional tirzepatide-derived GLP-1/GIP receptor agonist fused to IgG4 Fc in their milk at 0.8-1.42 g/L, offering a potential alternative production platform.","whyItMatters":"GLP-1 drug shortages are a real problem. Producing these peptides in animal milk could supplement traditional manufacturing.","specificNumbers":"Tirzepatide-derived peptide-IgG4 Fc fusion; 0.8-1.42 g/L in milk; goat beta-casein promoter; mammary-specific expression in two founder lines.","methodology":"Transgenic mouse generation using goat beta-casein promoter constructs. Protein expression quantification in milk.","limitations":"Mouse model for proof of concept; commercial production would require larger animals (goats, cows). Protein folding and activity verification needed. Regulatory complexity for animal-derived biologics."},{"rthcId":"RPEP-13204","title":"Enhanced FGF21 Delivery via Neutrophil-Membrane-Coated Nanoparticles Improves Therapeutic Efficacy for Myocardial Ischemia-Reperfusion Injury.","authors":"Rao, Zhiheng; Tang, Yuli; Zhu, Jiamei; Lu, Zhenzhen; Chen, Zhichao; Wang, Jiaojiao; Bao, Yuxuan; Mukondiwa, Alan Vengai; Wang, Cong; Wang, Xiaojie; Luo, Yongde; Li, Xiaokun","year":2025,"journal":"Nanomaterials (Basel, Switzerland), 15(5)","doi":"10.3390/nano15050346","pmid":"40072149","tags":["drug-delivery-systems","cardiovascular-effects"],"studyType":"animal-study","evidenceStrength":"low-moderate","keyFinding":"Neutrophil-membrane-coated nanoparticles loaded with FGF21 reduced heart damage after ischemia-reperfusion in mice by targeting inflamed cardiac tissue.","whyItMatters":"FGF21 is a metabolic regulator (like GLP-1 drugs) that protects the heart. Wrapping it in neutrophil membranes helps it reach damaged heart tissue more effectively.","specificNumbers":"Neutrophil-membrane coated liposomal NPs with FGF21; tested in mouse ischemia-reperfusion model; improved cardiac outcomes vs uncoated NPs.","methodology":"Nanoparticle fabrication, neutrophil membrane coating, characterization, and in vivo testing in mouse I/R injury model.","limitations":"Mouse model. Complex manufacturing process. Long-term safety of neutrophil-coated particles unknown. FGF21 may have off-target effects."},{"rthcId":"RPEP-13205","title":"Bioactive compounds from food-grade Bacillus.","authors":"Raphel, Steji; Halami, Prakash Motiram","year":2025,"journal":"Journal of the science of food and agriculture, 105(8), 4085-4095","doi":"10.1002/jsfa.13935","pmid":"39373131","tags":["antimicrobial-peptides","bioactive-peptides"],"studyType":"narrative-review","evidenceStrength":"low-moderate","keyFinding":"Food-grade Bacillus species produce diverse bioactive compounds including antimicrobial peptides, non-ribosomal peptides, and enzymes with antioxidant, antibacterial, and cholesterol-lowering properties.","whyItMatters":"Bacillus strains already used in food fermentation could serve as factories for bioactive peptides, improving functional food development.","specificNumbers":"No specific data; reviews multiple bioactive compound classes from food-grade Bacillus strains.","methodology":"Narrative review of bioactive compound production by food-grade Bacillus species.","limitations":"Review format. Many compounds identified in lab conditions may not reach effective levels in food products. Regulatory status varies by country."},{"rthcId":"RPEP-13206","title":"Permeation Enhancer-based Ionogel Shows Remarkable Potential for Oral Insulin Delivery.","authors":"Raptis, Konstantinos; Heade, Joanne; Cunha, Cristiana; van de Weert, Marco; Saaby, Lasse; Rønholt, Stine; Nielsen, Hanne Mørck","year":2025,"journal":"Advanced healthcare materials, 14(20), e2500946","doi":"10.1002/adhm.202500946","pmid":"40492897","tags":["insulin-peptides","drug-delivery-systems"],"studyType":"animal-study","evidenceStrength":"low-moderate","keyFinding":"A choline decanoate-based ionic liquid gel formulation enabled sustained oral insulin absorption in vivo, showing promise for replacing insulin injections.","whyItMatters":"Oral insulin delivery has been a goal for decades. This gel-like formulation uses a permeation enhancer ionic liquid to overcome the gut absorption barrier for peptide drugs.","specificNumbers":"Choline decanoate 1:2 ratio; gel-like rheology; slow in vitro dissolution; sustained in vivo insulin absorption.","methodology":"Ionic liquid synthesis, rheological characterization, in vitro dissolution, and in vivo oral insulin absorption studies in animals.","limitations":"Animal study. Bioavailability compared to injected insulin not quantified in abstract. Long-term GI safety of ionic liquid unknown. Scale-up challenges."},{"rthcId":"RPEP-13207","title":"Cost-effectiveness of abortive and preventative treatments in patients with migraine: a systematic review.","authors":"Rashidi, Arefe; Keramati, Mohammadreza; Esmaily, Hadi; Talebi, Maryam; Mohammadnezhad, Ghader","year":2025,"journal":"European journal of clinical pharmacology, 81(10), 1381-1399","doi":"10.1007/s00228-025-03881-z","pmid":"40663117","tags":["cgrp-peptides","migraine-headache","clinical-applications"],"studyType":"systematic-review","evidenceStrength":"moderate","keyFinding":"CGRP inhibitors for migraine prevention are generally cost-effective at standard willingness-to-pay thresholds, though high drug costs remain a concern in some healthcare settings.","whyItMatters":"CGRP drugs are expensive. This systematic review helps payers and clinicians understand whether the clinical benefits justify the costs across different countries.","specificNumbers":"Studies from 2014-2024; ICERs and QALYs reported; CGRP inhibitors generally cost-effective at standard thresholds.","methodology":"Systematic review of full economic evaluations (cost-effectiveness, cost-utility) of migraine treatments.","limitations":"Heterogeneous study methods and settings. Most studies industry-sponsored. Real-world costs may differ from modeled costs. Drug prices continue to change."},{"rthcId":"RPEP-13208","title":"Glucagon-like Peptide-1 receptor agonist use is not associated with increased reoperation risk following rotator cuff repair.","authors":"Rasmussen, Spencer T; Ilyas, Asif M","year":2025,"journal":"Journal of orthopaedics, 70, 235-240","doi":"10.1016/j.jor.2025.08.016","pmid":"40895356","tags":["glp-1-receptor-agonists","clinical-applications","muscle-bone-joint"],"studyType":"cohort","evidenceStrength":"moderate","keyFinding":"GLP-1 receptor agonist use for at least 3 months before rotator cuff repair was not associated with increased reoperation risk compared to non-users.","whyItMatters":"Some worry GLP-1 drugs might impair tissue healing. This study found no increased risk of needing repeat shoulder surgery.","specificNumbers":"TriNetX database 2014-2024; GLP-1 use >=3 months pre-RCR; no increased reoperation risk vs non-users; propensity-matched.","methodology":"Retrospective cohort analysis using TriNetX with propensity score matching.","limitations":"Retrospective. Claims data cannot capture all confounders. Reoperation is a crude outcome measure. Does not assess healing quality."},{"rthcId":"RPEP-13209","title":"Benefit of Semaglutide in Symptomatic Peripheral Artery Disease by Baseline Type 2 Diabetes Characteristics: Insights From STRIDE, a Randomized, Placebo-Controlled, Double-Blind Trial.","authors":"Rasouli, Neda; Guder Arslan, Ecenur; Catarig, Andrei-Mircea; Houlind, Kim; Ludvik, Bernhard; Nordanstig, Joakim; Sourij, Harald; Thomas, Sebastian; Verma, Subodh; Bonaca, Marc P","year":2025,"journal":"Diabetes care, 48(9), 1529-1535","doi":"10.2337/dc25-1082","pmid":"40543068","tags":["glp-1-receptor-agonists","cardiovascular-effects","clinical-applications"],"studyType":"rct","evidenceStrength":"moderate-high","keyFinding":"In the STRIDE trial, semaglutide 1.0 mg improved walking distance and symptoms in people with peripheral artery disease and type 2 diabetes regardless of diabetes duration, BMI, HbA1c, or diabetes medications.","whyItMatters":"Peripheral artery disease makes walking painful. Semaglutide improved function across all diabetes subgroups, suggesting broad applicability.","specificNumbers":"STRIDE trial (NCT04560998); semaglutide 1.0 mg weekly; 52-week treadmill testing; consistent MWD and PFWD improvements across all diabetes subgroups.","methodology":"Prespecified subgroup analysis of a randomized, placebo-controlled, double-blind trial by diabetes duration, BMI, HbA1c, and medication use.","limitations":"Subgroup analysis with limited power for interaction tests. Single trial. Does not prove semaglutide directly improves leg blood flow vs weight loss effect."},{"rthcId":"RPEP-13210","title":"Tirzepatide for Older Adults with Type 2 Diabetes and Without Obesity: A Post Hoc Analysis of the SURPASS Clinical Trials.","authors":"Rasouli, Neda; Wilding, John P H; Kwan, Anita Y M; Paik, Jim S; Sharma, Palash; Peleshok, Jennifer","year":2025,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 16(4), 701-715","doi":"10.1007/s13300-025-01711-0","pmid":"40016573","tags":["glp-1-receptor-agonists","gip-receptor","clinical-applications"],"studyType":"rct","evidenceStrength":"moderate-high","keyFinding":"In a post hoc analysis of SURPASS trials, tirzepatide was effective and safe in older adults (>=65) with T2D who were not obese (BMI <30), achieving clinically meaningful HbA1c reductions and weight loss.","whyItMatters":"Many older diabetes patients are not obese. This analysis confirms tirzepatide works well in this understudied group.","specificNumbers":"Pooled SURPASS-1 to -5; subgroup >=65 years with BMI <30; maintained HbA1c and weight efficacy; safety comparable to overall population.","methodology":"Post hoc subgroup analysis of pooled data from five phase 3 randomized controlled trials.","limitations":"Post hoc analysis. Small subgroup. Trials not designed for this population. Weight loss in non-obese elderly raises muscle mass concerns."},{"rthcId":"RPEP-13211","title":"The hormonal regulation of men's sexual desire, arousal, and penile erection: recommendations from the fifth international consultation on sexual medicine (ICSM 2024).","authors":"Rastrelli, Giulia; Antonio, Leen; Carrier, Serge; Isidori, Andrea; Maggi, Mario","year":2025,"journal":"Sexual medicine reviews, 13(4), 433-455","doi":"10.1093/sxmrev/qeaf025","pmid":"40519205","tags":["kisspeptin","oxytocin","melanocortin-peptides"],"studyType":"guideline","evidenceStrength":"moderate-high","keyFinding":"The 2024 ICSM recommends assessing kisspeptin, alpha-MSH, and oxytocin (among other hormones) when evaluating men with low sexual desire or erectile dysfunction, based on new evidence for their roles in sexual function.","whyItMatters":"These neuropeptides are emerging as important regulators of male sexual function beyond traditional testosterone-focused approaches.","specificNumbers":"ICSM 2024 guidelines; graded recommendations (strong/moderate/conditional); covers kisspeptin, alpha-MSH, oxytocin, and other hormones.","methodology":"International expert panel review with evidence-based recommendation grading system (ICSM 2024).","limitations":"Some neuropeptide research is still preliminary. Clinical assays for kisspeptin and alpha-MSH not widely available. Guidelines may change as evidence evolves."},{"rthcId":"RPEP-13212","title":"Mechanistic Insights Into the Cardioprotective Effects of Modern Glucose-Lowering Drugs in Type 2 Diabetes: A Systematic Review.","authors":"Ratnala, Mounica; Johal, Loveleen K; Galadima, Zulaihat F; Janjua, Fatima F; Trejos Guzman, Katherine S; Lal, Kirshan; Fatima, Maryam; Khan, Mashal; Mallick, Maryem; Yadav, Sunil; Sarwar, Muhammad Usman; Khan, Riaz","year":2025,"journal":"Cureus, 17(9), e93284","doi":"10.7759/cureus.93284","pmid":"41146812","tags":["glp-1-receptor-agonists","sglt2-inhibitors","cardiovascular-effects"],"studyType":"systematic-review","evidenceStrength":"moderate-high","keyFinding":"GLP-1 RAs and SGLT2 inhibitors protect the heart through overlapping but distinct mechanisms: reduced oxidative stress, improved endothelial function, favorable cardiac remodeling, and anti-inflammatory effects.","whyItMatters":"Understanding the mechanistic differences between these drug classes helps guide combination therapy and personalized treatment.","specificNumbers":"PRISMA-guided review through Feb 2025; includes RCTs and mechanistic studies; covers oxidative stress, remodeling, endothelial function, and inflammation.","methodology":"Systematic review per PRISMA guidelines. PubMed, Embase, Scopus, and Cochrane searched. Included RCTs and prospective mechanistic studies.","limitations":"Mechanistic biomarkers are surrogates. Long-term clinical outcome correlations not always established. Heterogeneous study designs."},{"rthcId":"RPEP-13213","title":"Medication underuse in real-life practice: the impact of galcanezumab towards achieving very low frequency episodic migraine in a southeast Asian middle-income nation.","authors":"Rattanawong, Wanakorn; Anukoolwittaya, Prakit; Hiransuthikul, Akarin; Pongpitakmetha, Thanakit; Trisataya, Auranee; Thanprasertsuk, Sekh; Rapoport, Alan","year":2025,"journal":"The journal of headache and pain, 26(1), 13","doi":"10.1186/s10194-025-01952-1","pmid":"39825238","tags":["cgrp-peptides","migraine-headache","clinical-applications"],"studyType":"observational","evidenceStrength":"low-moderate","keyFinding":"In Thailand, galcanezumab helped high-frequency episodic and chronic migraine patients achieve very low-frequency episodic migraine, with better results when started earlier in the disease course.","whyItMatters":"Starting CGRP antibodies earlier in migraine progression may prevent chronification. The concept of \"medication underuse headache\" argues for earlier intervention.","specificNumbers":"Single-center Thailand cohort (2023-onwards); galcanezumab for HFEM and CM; VLFEM achievement as outcome; better response with earlier initiation.","methodology":"Retrospective real-world cohort study at a single center in Thailand.","limitations":"Single center. Retrospective. Thai population may differ from Western populations. No control group. Selection bias likely."},{"rthcId":"RPEP-13214","title":"FRONTIER: FReeStyle Libre system use in Ontario among people with diabetes in the IC/ES database-Evidence from real-world practice: Patients on basal insulin, glucagon-like peptide 1 receptor agonist or oral therapies.","authors":"Ratzki-Leewing, Alexandria; Harris, Stewart B; Rabasa-Lhoret, Rémi; Poon, Yeesha","year":2025,"journal":"Diabetes, obesity & metabolism, 27(5), 2637-2646","doi":"10.1111/dom.16266","pmid":"40117297","tags":["glp-1-receptor-agonists","type-2-diabetes","real-world-evidence"],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"People with type 2 diabetes who started using FreeStyle Libre glucose monitors saw lower HbA1c levels and fewer emergency visits over 24 months, regardless of whether they used insulin, GLP-1 drugs, or oral medications alone.","whyItMatters":"Continuous glucose monitoring helped improve blood sugar control across all treatment types. This suggests the technology benefits a wide range of people with type 2 diabetes, not just those on insulin.","specificNumbers":"20,253 patients studied. HbA1c dropped 0.3% to 0.8% across groups. Follow-up lasted 24 months.","methodology":"Retrospective analysis of administrative health records from Ontario, Canada. Compared HbA1c and healthcare use 12 months before and 12-24 months after starting FreeStyle Libre.","limitations":"Observational design cannot prove the monitors caused the improvements. No control group without monitors. Patients who stayed on monitors for 24 months may be more motivated than average."},{"rthcId":"RPEP-13215","title":"Glucagon-like peptide-1 receptor agonists reduce atrial fibrillation among patients with heart failure with preserved and mildly reduced ejection fraction - a meta-analysis of randomized controlled trials.","authors":"Ravikulan, Rohanti; Chavali, Sanjay; Gunton, James E; De Pasquale, Carmine G","year":2025,"journal":"European journal of heart failure, 27(11), 2211-2217","doi":"10.1002/ejhf.70085","pmid":"41216984","tags":["glp-1-receptor-agonists","semaglutide","cardiovascular-outcomes","heart-failure"],"studyType":"meta-analysis","evidenceStrength":"moderate-high","keyFinding":"GLP-1 receptor agonists cut the risk of new atrial fibrillation by 46% in patients with heart failure with preserved or mildly reduced ejection fraction, based on pooled data from four randomized trials.","whyItMatters":"Atrial fibrillation is especially common in this type of heart failure and worsens outcomes. Finding that GLP-1 drugs may prevent it adds a new potential benefit beyond weight loss and blood sugar control.","specificNumbers":"Risk ratio 0.54 (95% CI 0.36-0.81, p = 0.003). 3,743 patients across 4 trials (SELECT, FLOW, STEP-HFpEF, STEP-HFpEF DM).","methodology":"Systematic review and meta-analysis of randomized controlled trials. Searched MEDLINE, Embase, and Cochrane through February 2025. Used fixed-effect model for primary analysis.","limitations":"Only four trials met criteria. Moderate heterogeneity (I-squared = 51%). Atrial fibrillation was not a primary endpoint in any included trial. Dedicated trials with adjudicated AF outcomes are needed."},{"rthcId":"RPEP-13216","title":"Tirzepatide did not impact metabolic adaptation in people with obesity, but increased fat oxidation.","authors":"Ravussin, Eric; Sanchez-Delgado, Guillermo; Martin, Corby K; Beyl, Robbie A; Greenway, Frank L; O'Farrell, Libbey S; Roell, William C; Qian, Hui-Rong; Li, Jing; Nishiyama, Hiroshi; Haupt, Axel; Pratt, Edward J; Urva, Shweta; Milicevic, Zvonko; Coskun, Tamer","year":2025,"journal":"Cell metabolism, 37(5), 1060-1074.e4","doi":"10.1016/j.cmet.2025.03.011","pmid":"40203836","tags":["tirzepatide","glp-1-receptor-agonists","gip-receptor","obesity-treatment","weight-management"],"studyType":"clinical-trial","evidenceStrength":"moderate-high","keyFinding":"Tirzepatide increased fat burning but did not prevent the metabolic slowdown that normally happens during weight loss in people with obesity. In mice, tirzepatide did reduce metabolic adaptation.","whyItMatters":"When people lose weight, their bodies burn fewer calories. This 'metabolic adaptation' makes it harder to keep losing weight. This study shows tirzepatide works mainly by reducing appetite and shifting the body toward burning fat, not by preventing metabolic slowdown.","specificNumbers":"Results from a phase 1 clinical trial (NCT04081337). Specific magnitude of fat oxidation increase and calorie intake reduction reported but exact numbers require full-text access.","methodology":"Combined preclinical mouse study with a phase 1, randomized, placebo-controlled clinical trial in people with obesity. Measured energy expenditure, respiratory exchange ratio, appetite, and calorie intake.","limitations":"Phase 1 trial with small sample size. Mouse results did not fully translate to humans. Short-term study design limits conclusions about long-term metabolic effects."},{"rthcId":"RPEP-13217","title":"The impact of CGRP monoclonal antibodies on cytokine expression in chronic migraine: a cohort study.","authors":"Ray, Jason C; McDonald, Stuart; Todaro, Marian; Baker, Josephine; Yeh, Wei Zhen; Hutton, Elspeth J; Matharu, Manjit; Butzkueven, Helmut","year":2025,"journal":"Journal of neurology, 272(10), 649","doi":"10.1007/s00415-025-13400-w","pmid":"40991059","tags":["cgrp-peptides","cgrp-monoclonal-antibodies","migraine","safety-and-side-effects"],"studyType":"observational","evidenceStrength":"low-moderate","keyFinding":"CGRP monoclonal antibodies did not cause significant changes in plasma cytokine levels in chronic migraine patients after three months of treatment, easing concerns about immune system activation.","whyItMatters":"Some reports have raised the possibility that blocking CGRP might trigger inflammation. This study found no evidence of broad immune activation, suggesting these drugs do not shift the immune system toward a pro-inflammatory state.","specificNumbers":"22 chronic migraine patients and 10 healthy controls. 10 cytokines measured. No significant overall change (Wilk's lambda 0.528, p = 0.448). IL-5 decreased (p = 0.020).","methodology":"Prospective cohort study at a tertiary headache center. Used Simoa CorPlex 10-plex cytokine assay at baseline and 3 months. Included healthy control group at single time point.","limitations":"Very small sample size (22 patients). Only 3 months of follow-up. Single-center study. Healthy controls measured at one time point only, so natural variation was not tracked."},{"rthcId":"RPEP-13218","title":"Patient Adherence and Long-Term Tolerability of Anti-calcitonin Gene-Related Peptide (CGRP) Monoclonal Antibodies in Migraine Prevention: A Systematic Review.","authors":"Ray, Rubela; Virk, Ghazala S; Regmi, Nishchal; Shafiq, Muhammad Muddassar; Siddique, Rumaisa; Elfatih Elamin, Ahmed; Jihad, Yousif; Ali, Aasim; Devi, Hema; Essani, Binish","year":2025,"journal":"Cureus, 17(8), e91347","doi":"10.7759/cureus.91347","pmid":"41035604","tags":["cgrp-peptides","cgrp-monoclonal-antibodies","migraine","safety-and-side-effects"],"studyType":"systematic-review","evidenceStrength":"moderate-high","keyFinding":"Anti-CGRP monoclonal antibodies showed about 55% adherence at 12 months, much higher than the roughly 35% seen with oral migraine preventives. Discontinuation from side effects ranged from 6% to 20%.","whyItMatters":"Migraine preventive medications often fail because people stop taking them. CGRP antibodies appear to keep patients on treatment longer, and their response rates actually improve over time rather than fading.","specificNumbers":"12-month adherence about 55% vs. 35% for oral preventives. Discontinuation from adverse events 5.9%-20%. Responder rates (50%+ reduction in migraine days): 44% at 3 months, 64% at 12 months. Over 50,000 patients across 11 studies.","methodology":"Systematic review following PRISMA guidelines. Searched PubMed, Embase, CENTRAL, Scopus, and Web of Science (2018-2024). Included RCTs, real-world studies, and prior systematic reviews.","limitations":"No direct head-to-head RCTs comparing CGRP antibodies to topiramate or onabotulinumtoxinA. Limited data beyond 12 months. Cost-effectiveness and use in pregnancy not well studied."},{"rthcId":"RPEP-13219","title":"Utilization patterns of glucagon like Peptide-1 receptor agonists prior to bariatric and metabolic surgery: a multicenter study.","authors":"Rayman, Shlomi; Morduch, Evyatar; Reiner-Benaim, Anat; Catzman, Netta-Lee; Carmeli, Idan; Froylich, Dvir; Goitein, David","year":2025,"journal":"Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery, 21(2), 121-126","doi":"10.1016/j.soard.2024.09.010","pmid":"39516068","tags":["glp-1-receptor-agonists","semaglutide","liraglutide","obesity-treatment","bariatric-surgery"],"studyType":"observational","evidenceStrength":"low-moderate","keyFinding":"Among 434 bariatric surgery candidates in Israel, 63% had previously tried GLP-1 receptor agonists. Over 95% stopped the drugs before surgery due to insufficient weight loss or side effects.","whyItMatters":"Many people seeking bariatric surgery have already tried GLP-1 medications without adequate results. This suggests GLP-1 drugs and surgery serve different patient populations, and prior GLP-1 failure may be common among surgical candidates.","specificNumbers":"434 candidates. 63% had GLP-1 RA history. Median weight loss 5.38 kg. Mean use duration 19 weeks. GI side effects in 57.8%. Over 95% discontinued. Liraglutide: 5.9 vs 3.9 kg at max dose vs not (p = 0.03). Semaglutide: 6.5 vs 2.5 kg (p = 0.016).","methodology":"Retrospective multicenter study across five high-volume bariatric surgery centers in Israel. Collected data from February to September 2023.","limitations":"Retrospective design with self-reported medication history. Short study period. Single country. Doses and durations varied widely. Selection bias toward surgical candidates who already failed medical therapy."},{"rthcId":"RPEP-13220","title":"Medical Management of Obesity: A Comprehensive Review of Food and Drug Administration (FDA)-Approved and Investigational Therapies.","authors":"Raza, Syed S; Zakir, Zarshal; Hashmat, Ahmad; Awan, Saira K; Varrassi, Giustino","year":2025,"journal":"Cureus, 17(11), e96739","doi":"10.7759/cureus.96739","pmid":"41393574","tags":["glp-1-receptor-agonists","semaglutide","tirzepatide","obesity-treatment","oral-peptide-delivery","drug-development-pipeline"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"This review covers all FDA-approved obesity medications and next-generation drugs in development, noting that semaglutide and tirzepatide have redefined weight loss expectations while oral and multi-receptor agonists show even greater potential.","whyItMatters":"The obesity treatment landscape is changing fast. Newer GLP-1 drugs produce far more weight loss than older options. Next-generation agents like orforglipron and retatrutide may push results even further.","specificNumbers":"Not specified in abstract. References semaglutide, tirzepatide, orforglipron, and retatrutide efficacy from published trials.","methodology":"Narrative review synthesizing evidence on FDA-approved and investigational obesity therapies. Covers mechanisms, efficacy, safety, and prescribing guidance.","limitations":"Narrative review, not systematic. No pooled quantitative analysis. Investigational agents have limited long-term data. May not capture all emerging therapies."},{"rthcId":"RPEP-13221","title":"Allocation of Semaglutide According to Coronary Artery Calcium and BMI: Applying the SELECT Trial to MESA.","authors":"Razavi, Alexander C; Cao Zhang, Alexander M; Dardari, Zeina A; Nasir, Khurram; Khorsandi, Michael; Mortensen, Martin Bødtker; Al-Mallah, Mouaz H; Shapiro, Michael D; Daubert, Melissa A; Blumenthal, Roger S; Sperling, Laurence S; Whelton, Seamus P; Blaha, Michael J; Dzaye, Omar","year":2025,"journal":"JACC. Cardiovascular imaging, 18(4), 451-461","doi":"10.1016/j.jcmg.2024.10.004","pmid":"39797878","tags":["semaglutide","glp-1-receptor-agonists","cardiovascular-outcomes"],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"Using coronary artery calcium (CAC) scores to guide semaglutide prescribing could dramatically improve cost-effectiveness. The number needed to treat to prevent one cardiovascular event dropped from 653 (CAC = 0) to 79 (CAC 300+).","whyItMatters":"Semaglutide is expensive and in limited supply. CAC scoring could help doctors identify which patients without diabetes or known heart disease would benefit most, making better use of a scarce resource.","specificNumbers":"3,129 MESA participants. Mean age 61.2 years, 54% female, 62% non-White, mean BMI 31.8. CAC 300+ vs. 0: MACE HR 2.16, HF HR 2.80, CKD HR 1.59, mortality HR 1.35. NNT for MACE: 653 (CAC=0) vs. 79 (CAC 300+).","methodology":"Applied SELECT trial risk reduction estimates to observed event rates in MESA cohort. Used Cox regression to assess CAC-outcome associations. Calculated 5-year number-needed-to-treat.","limitations":"Modeled analysis, not a randomized trial of CAC-guided prescribing. SELECT enrolled people with established cardiovascular disease or risk factors, so applying its results to MESA participants involves assumptions. CAC scoring adds cost and radiation exposure."},{"rthcId":"RPEP-13222","title":"GLP-1 receptor agonists and pancreatic beta cell apoptosis in diabetes mellitus: a systematic review and meta-analysis of preclinical studies.","authors":"Rea, Nicolas; Ramdass, Prakash V A K","year":2025,"journal":"Frontiers in clinical diabetes and healthcare, 6, 1579961","doi":"10.3389/fcdhc.2025.1579961","pmid":"40937349","tags":["glp-1-receptor-agonists","type-2-diabetes","beta-cell-function","preclinical-research"],"studyType":"meta-analysis","evidenceStrength":"low-moderate","keyFinding":"GLP-1 receptor agonists reduced pancreatic beta cell death by about 10 percentage points in preclinical models, supporting the idea that these drugs help preserve insulin-producing cells.","whyItMatters":"Diabetes involves the gradual loss of beta cells that make insulin. If GLP-1 drugs can slow this loss, they may do more than just control blood sugar. They could help protect the pancreas itself.","specificNumbers":"Pooled mean difference in apoptosis: -0.10 (95% CI -0.15 to -0.05, p = 0.0003). 5 studies included. I-squared = 100% (extreme heterogeneity). Egger's test p = 0.80 (no publication bias detected).","methodology":"Systematic review and meta-analysis following PRISMA guidelines. Searched Scopus, PubMed, Embase, and Google Scholar. Included preclinical studies of GLP-1 RA effects on human beta cell apoptosis. Random-effects model.","limitations":"Only five studies met criteria. Extreme heterogeneity (I-squared = 100%) limits confidence in the pooled estimate. All preclinical data from cell cultures. No human clinical evidence. Long-term effects on beta cell function unknown."},{"rthcId":"RPEP-13223","title":"Effects of oral semaglutide on cardiovascular outcomes: A systematic review and meta-analysis.","authors":"Rebelo, Thiago Gorayeb; de Araujo Paysano, Maria Lúcia Brito; Matheus, Gustavo Tadeu Freitas Uchôa; Ribeiro, Danilo Monteiro; Said, Thomas Benevides; Kelly, Francinny Alves","year":2025,"journal":"International journal of cardiology, 440, 133683","doi":"10.1016/j.ijcard.2025.133683","pmid":"40752805","tags":["semaglutide","glp-1-receptor-agonists","oral-peptide-delivery","cardiovascular-outcomes","type-2-diabetes"],"studyType":"meta-analysis","evidenceStrength":"high","keyFinding":"Oral semaglutide reduced the risk of major cardiovascular events by 14-15% compared to placebo in people with type 2 diabetes, based on five randomized trials with nearly 14,000 patients.","whyItMatters":"Injectable GLP-1 drugs already have proven heart benefits. This confirms the oral pill form of semaglutide also protects the heart, which could make this benefit accessible to more patients who prefer pills over injections.","specificNumbers":"13,875 total patients (6,935 oral semaglutide, 6,940 placebo). Cardiovascular events RR 0.86 (95% CI 0.78-0.95, p = 0.0029, I-squared = 0%). HR 0.85 (95% CI 0.77-0.95). 5 RCTs included.","methodology":"Systematic review and meta-analysis of randomized controlled trials. Searched major databases through May 2025. Statistical analysis in RStudio with heterogeneity assessed via I-squared.","limitations":"Individual outcomes (stroke, MI, cardiovascular death, all-cause mortality) were not significant. Cannot determine which specific cardiovascular events are most reduced. All trials compared to placebo, not active comparators."},{"rthcId":"RPEP-13224","title":"Glucagon-like peptide-1 receptor agonists as add-on therapy to insulin for type 1 diabetes mellitus: a systematic review and meta-analysis.","authors":"Rebelos, Eleni; Anastasiou, Ioanna A; Tentolouris, Nikolaos; Karagiannis, Thomas; Tsapas, Apostolos; Ferrannini, Ele; Liakos, Aris","year":2025,"journal":"Hormones (Athens, Greece), 24(4), 1141-1151","doi":"10.1007/s42000-025-00704-9","pmid":"40760325","tags":["glp-1-receptor-agonists","type-1-diabetes","insulin-therapy"],"studyType":"meta-analysis","evidenceStrength":"high","keyFinding":"Adding GLP-1 receptor agonists to insulin in type 1 diabetes reduced HbA1c by 0.23%, body weight by 3.93 kg, and daily insulin dose by 5.74 units without increasing severe hypoglycemia risk.","whyItMatters":"People with type 1 diabetes must take insulin but often struggle with weight gain and high doses. GLP-1 drugs offer modest improvements in blood sugar and meaningful weight loss without adding dangerous low blood sugar episodes.","specificNumbers":"25 RCTs. HbA1c MD -0.23% (95% CI -0.30 to -0.17). Weight MD -3.93 kg (95% CI -4.29 to -3.56). Insulin dose MD -5.74 U/day (95% CI -7.30 to -4.19). No increased severe hypoglycemia (13 studies).","methodology":"Systematic review and meta-analysis. Searched PubMed and Cochrane through November 2023. RCTs with 12+ weeks for primary outcomes, 4+ weeks for secondary outcomes. Random-effects model.","limitations":"GLP-1 RAs are not approved for type 1 diabetes. Time-in-range did not improve despite lower HbA1c. Did not prevent progressive C-peptide loss. Heterogeneity across trials in agents, doses, and populations."},{"rthcId":"RPEP-13225","title":"Salcaprozate-based ionic liquids for GLP-1 gastric delivery: A mechanistic understanding of in vivo performance.","authors":"Rebollo, René; Niu, Zhigao; Blaabjerg, Lasse; La Zara, Damiano; Juel, Trine; Pedersen, Henrik Duelund; Andersson, Vincent; Benova, Michaela; Krogh, Camilla; Pons, Raphaël; Holm, Tobias Palle; Wahlund, Per-Olof; Fan, Li; Wang, Zhuoran; Kennedy, Adam; Kuhre, Rune Ehrenreich; Christophersen, Philip; Bardonnet, Pierre-Louis; Sassene, Philip Jonas","year":2025,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 377, 267-276","doi":"10.1016/j.jconrel.2024.11.036","pmid":"39566853","tags":["glp-1-receptor-agonists","oral-peptide-delivery","drug-development-pipeline","preclinical-research"],"studyType":"preclinical","evidenceStrength":"low","keyFinding":"A salcaprozate-based ionic liquid formulation delivered a GLP-1 analogue faster through the stomach lining than standard tablets in rats and anesthetized dogs, but showed lower overall absorption in awake dogs due to gastric fluid dilution and rapid emptying.","whyItMatters":"Oral peptide drugs like semaglutide require patients to fast and wait before eating. A liquid formulation that works faster could be more convenient, but keeping the drug in contact with the stomach lining long enough remains a challenge.","specificNumbers":"Peptide loading and release rates characterized in vitro. Storage stable for 3 weeks at 4 degrees C. Faster absorption onset vs. tablet in rats and anesthetized dogs. Lower overall exposure in awake dogs.","methodology":"In vitro characterization of ionic liquid formulation. In vivo pharmacokinetic studies in rats, anesthetized dogs, and awake dogs. Compared to tablet reference formulation.","limitations":"Animal studies only. Awake dog results showed inferior overall absorption. Gastric physiology (fluid dilution, rapid liquid transit) poses major hurdles. Single GLP-1 analogue tested. No human data."},{"rthcId":"RPEP-13226","title":"Engineered lipid nanoparticles loaded with LL-37 peptide as inhalable drug delivery carriers for the treatment of bacterial infections.","authors":"Reczyńska-Kolman, Katarzyna; Ochońska, Dorota; Brzychczy-Włoch, Monika; Pamuła, Elżbieta","year":2025,"journal":"Biomaterials advances, 176, 214363","doi":"10.1016/j.bioadv.2025.214363","pmid":"40466415","tags":["antimicrobial-peptides","drug-delivery-systems","preclinical-research"],"studyType":"preclinical","evidenceStrength":"low","keyFinding":"Lipid nanoparticles loaded with the antimicrobial peptide LL-37 penetrated lung mucus, protected lung cells from peptide toxicity, and disrupted Pseudomonas aeruginosa biofilms at lower doses than free LL-37.","whyItMatters":"LL-37 is a natural human defense peptide that kills bacteria, but delivering it to the lungs is difficult. Packaging it in tiny fat particles could make inhaled LL-37 a practical treatment for lung infections.","specificNumbers":"Particle diameter 35-42 nm. Encapsulation efficiency about 30%. Max peptide loading 6.1%. Biofilm LD50: 103 micrograms/mL (nanoparticles) vs. 310 micrograms/mL (free LL-37).","methodology":"Emulsification method to prepare cetyl palmitate nanoparticles. Characterized size, charge, mucus penetration, and cytotoxicity. Tested antibiofilm activity against Pseudomonas aeruginosa. Used air-liquid interface lung cell model.","limitations":"In vitro and bench studies only. No animal or human testing. Single bacterial species tested. Encapsulation efficiency was only 30%. Long-term stability and in vivo lung deposition not assessed."},{"rthcId":"RPEP-13227","title":"Dual Proteomics Strategies to Dissect and Quantify the Components of Nine Medically Important African Snake Venoms.","authors":"Redureau, Damien; Amorim, Fernanda Gobbi; Crasset, Thomas; Berger, Imre; Schaffitzel, Christiane; Menzies, Stefanie Kate; Casewell, Nicholas R; Quinton, Loïc","year":2025,"journal":"Toxins, 17(5)","doi":"10.3390/toxins17050243","pmid":"40423326","tags":["venom-derived-peptides","preclinical-research","peptide-discovery"],"studyType":"laboratory","evidenceStrength":"low","keyFinding":"A dual proteomics approach identified and quantified venom components from nine medically important African snake species, revealing dominant toxin families and rare proteins not detected by standard methods.","whyItMatters":"Understanding exactly what is in snake venom helps develop better antivenoms. The improved technique found rare toxin components that standard methods miss, which could be important for designing targeted treatments.","specificNumbers":"9 snake species analyzed. Identified multiple toxin families including three-finger toxins, Kunitz-type proteins, metalloproteinases, phospholipases A2, hyaluronidases, and renin-like proteases.","methodology":"Shotgun venom proteomics combined with venom gland transcriptomics. Used Multi-Enzymatic Limited Digestion (MELD) technique to improve protein coverage. Standardized venomics workflow.","limitations":"Descriptive proteomics study without functional testing of identified toxins. Does not test whether findings improve antivenom efficacy. Species selection may not cover all medically relevant snakes in Africa."},{"rthcId":"RPEP-13228","title":"Neck pain in migraine: A narrative review and steps to correct evaluation and treatment.","authors":"Rees, Tayla A; Doukhi, Diana; Wang, Victor S; Balcerbula, Anita; Bravo, Michelle; Fathi, Haniyeh; Holmuratova, Bahtigul; Kodounis, Michalis; Seyoum, Seblewongel A; Tasdelen, Semih; Vekilyan, Hasmik; Caronna, Edoardo; Pozo-Rosich, Patricia","year":2025,"journal":"Cephalalgia : an international journal of headache, 45(10), 3331024251387449","doi":"10.1177/03331024251387449","pmid":"41134815","tags":["cgrp-peptides","migraine","cgrp-monoclonal-antibodies"],"studyType":"review","evidenceStrength":"low-moderate","keyFinding":"Neck pain in migraine is often misdiagnosed as a cervical spine disorder. It can be a migraine symptom, trigger, or coexisting condition, and shared neuroanatomical pathways between the neck and trigeminal system explain the overlap.","whyItMatters":"When neck pain is wrongly blamed on the cervical spine, migraine patients miss out on effective migraine treatments. Recognizing the connection could improve care for many people.","specificNumbers":"Not specified. Narrative review without pooled quantitative data.","methodology":"Narrative review of preclinical, clinical, neurophysiological, and imaging evidence. Searched PubMed. Proposes a structured clinical assessment approach and treatment algorithm.","limitations":"Narrative review, not systematic. No meta-analysis. Limited evidence on CGRP-targeted treatments for neck pain specifically. Proposed assessment algorithm has not been validated in clinical trials."},{"rthcId":"RPEP-13229","title":"Cholecystokinin: Clinical aspects of the new biology.","authors":"Rehfeld, Jens F","year":2025,"journal":"Journal of internal medicine, 298(3), 251-267","doi":"10.1111/joim.20110","pmid":"40557463","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13230","title":"Role of glucagon-like peptide-1 receptor agonists in pediatric obesity and metabolic dysfunction associated steatotic liver disease.","authors":"Rehman, Rahiya","year":2025,"journal":"World journal of clinical pediatrics, 14(3), 105731","doi":"10.5409/wjcp.v14.i3.105731","pmid":"40881096","tags":["glp-1-receptor-agonists","semaglutide","liraglutide","obesity-treatment","pediatric-use","liver-disease"],"studyType":"review","evidenceStrength":"low-moderate","keyFinding":"GLP-1 receptor agonists show promise for treating pediatric obesity and related fatty liver disease, but published data in children remain limited compared to the adult evidence base.","whyItMatters":"Childhood obesity and liver disease are growing problems. GLP-1 drugs work well in adults, but doctors need pediatric-specific evidence before widely prescribing them to children.","specificNumbers":"Not specified in abstract. References liraglutide, semaglutide, exenatide, and dulaglutide.","methodology":"Narrative review of pediatric obesity, MASLD pathophysiology, and GLP-1 receptor agonist literature in children and adolescents.","limitations":"Review article with limited primary pediatric data available. Most GLP-1 evidence comes from adult trials. Long-term safety in growing children is unknown."},{"rthcId":"RPEP-13231","title":"Moving beyond the scale: musculoskeletal risks, evidence gaps and emerging combination strategies to optimize the quality of weight loss pharmacotherapy in older adults.","authors":"Reid, Kieran F; Bhasin, Shalender","year":2025,"journal":"Frontiers in aging, 6, 1640030","doi":"10.3389/fragi.2025.1640030","pmid":"41209422","tags":["glp-1-receptor-agonists","obesity-treatment","weight-management","aging-and-peptides","safety-and-side-effects"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"GLP-1 receptor agonists cause significant weight loss in older adults but also reduce muscle mass, which threatens mobility and metabolic health. Combining them with exercise, nutrition, and muscle-building agents may preserve muscle during treatment.","whyItMatters":"Older adults lose muscle naturally with age. Adding rapid weight loss from GLP-1 drugs can accelerate this loss and increase fall risk. The review argues these drugs need to be paired with muscle-protective strategies in older patients.","specificNumbers":"Not specified in abstract. Discusses lean mass loss as a proportion of total weight loss with GLP-1 therapies.","methodology":"Narrative review covering musculoskeletal implications of obesity pharmacotherapy in older adults. Discusses weight regain, weight cycling, and combination treatment strategies.","limitations":"Narrative review without systematic search or meta-analysis. Limited clinical trial data specifically in older adults. Proposed combination strategies (GLP-1 plus promyogenic agents) are untested in controlled trials."},{"rthcId":"RPEP-13232","title":"New directions in childhood obesity treatment - A path forward or wishful thinking?","authors":"Reilly, Jessica L; Arora, Shruthi; Chatman, Kelsey; Cooper, Zenobia; Hsia, Daniel S","year":2025,"journal":"Journal of clinical lipidology, 19(4S), 54-60","doi":"10.1016/j.jacl.2025.05.010","pmid":"40975571","tags":["glp-1-receptor-agonists","obesity-treatment","pediatric-use"],"studyType":"review","evidenceStrength":"low-moderate","keyFinding":"GLP-1 agonists can produce over 15% weight loss in children aged 12 and older, and the AAP now endorses their use, but side effects, long-term unknowns, and access barriers remain significant concerns.","whyItMatters":"Childhood obesity has few effective treatments. GLP-1 drugs represent a major advance, but using potent weight loss medications in growing children raises unique safety questions that have not been fully answered.","specificNumbers":"Weight loss greater than 15% of baseline in clinical trials. Approved for ages 12 and older since 2020. AAP 2023 guidelines endorse use.","methodology":"Narrative review of GLP-1 agonist pharmacotherapy for childhood obesity. Covers approvals, clinical trial results, guidelines, side effects, and access barriers.","limitations":"Review article, not original research. Long-term safety data in children are lacking. Access and cost barriers limit real-world applicability. Effects on growth and development not fully characterized."},{"rthcId":"RPEP-13233","title":"Tirzepatide improves extracellular matrix integrity and vascularization in pancreatic islets of a mouse model of obesity, diabetes, and menopause.","authors":"Reis-Barbosa, Pedro H; Cardoso, Luiz Eduardo M; Mandarim-de-Lacerda, Carlos A","year":2025,"journal":"Biochemical and biophysical research communications, 790, 152913","doi":"10.1016/j.bbrc.2025.152913","pmid":"41191986","tags":["tirzepatide","glp-1-receptor-agonists","gip-receptor","beta-cell-function","preclinical-research"],"studyType":"animal-study","evidenceStrength":"low","keyFinding":"Tirzepatide reversed fibrosis, inflammation, and amyloid damage in pancreatic islets of female mice with obesity, diabetes, and surgical menopause, restoring blood vessel structure and protective matrix proteins.","whyItMatters":"In diabetes, pancreatic islets become scarred and lose their blood supply. This mouse study suggests tirzepatide may actively repair islet tissue rather than just slowing damage, which could be important for preserving insulin production.","specificNumbers":"Significant decreases in collagen types I and VI, MMP-2 and MMP-9, and CD44. Restored perlecan and heparan sulfate proteoglycans. Increased VEGF expression. Multivariate analysis identified tirzepatide as primary factor.","methodology":"Animal study in female mice with diet-induced obesity, streptozotocin-induced diabetes, and ovariectomy-induced menopause. Compared tirzepatide-treated, untreated, and control groups. Assessed extracellular matrix proteins, vascular markers, and transcripts by immunohistochemistry and gene expression.","limitations":"Mouse model only. Triple-stress model (obesity + diabetes + menopause) may not reflect typical human patients. Small group sizes typical of animal studies. No functional insulin secretion data reported. Translation to humans is uncertain."},{"rthcId":"RPEP-13234","title":"Weight Reduction with GLP-1 Agonists and Paths for Discontinuation While Maintaining Weight Loss.","authors":"Reiss, Allison B; Gulkarov, Shelly; Lau, Raymond; Klek, Stanislaw P; Srivastava, Ankita; Renna, Heather A; De Leon, Joshua","year":2025,"journal":"Biomolecules, 15(3)","doi":"10.3390/biom15030408","pmid":"40149944","tags":["glp-1-receptor-agonists","obesity-treatment","weight-management","safety-and-side-effects"],"studyType":"review","evidenceStrength":"low-moderate","keyFinding":"GLP-1 agonists reduce body weight by 15-25% over about one year, but most patients regain weight after stopping. The review discusses strategies for safe discontinuation while maintaining weight loss.","whyItMatters":"Weight regain after stopping GLP-1 drugs is one of the biggest challenges in obesity treatment. Finding ways to taper off these medications without losing progress is critical for long-term success.","specificNumbers":"40% of adults worldwide are overweight, 13% are obese. GLP-1 drugs reduce body weight by 15-25% after about 1 year. Boxed warning for medullary thyroid carcinoma and MEN2 history.","methodology":"Narrative review of GLP-1 agonist mechanisms, efficacy, adverse effects, and discontinuation strategies for obesity treatment.","limitations":"Review article without original data. No proven discontinuation protocols exist. Long-term data on weight maintenance after stopping are limited. Newer agents have very short track records."},{"rthcId":"RPEP-13235","title":"Genetically modeled GLP1R and GIPR agonism reduce binge drinking and alcohol-associated phenotypes: a multi-ancestry drug-target Mendelian randomization study.","authors":"Reitz, Joshua; Rosoff, Daniel B; Perlstein, Tyler; Wagner, Alexandra; Jung, Jeesun; Wagner, Josephin; Reiner, Benjamin C; Lohoff, Falk W","year":2025,"journal":"Molecular psychiatry, 30(12), 6119-6133","doi":"10.1038/s41380-025-03199-3","pmid":"40931165","tags":["glp-1-receptor-agonists","gip-receptor","tirzepatide","substance-use-and-addiction","cardiovascular-outcomes"],"studyType":"mendelian-randomization","evidenceStrength":"moderate","keyFinding":"Genetic variants mimicking GLP-1 and GIP receptor activation were linked to reduced binge drinking and heavy drinking with psychiatric comorbidities, but showed no effect on tobacco, cannabis, or opioid use disorders.","whyItMatters":"This genetic approach simulates the long-term effects of GLP-1/GIP drugs and suggests they may specifically reduce problematic alcohol use through appetite and metabolic pathways, not through a general effect on all addictive behaviors.","specificNumbers":"Binge drinking: beta = -0.44 (95% CI -0.72 to -0.15, p = 0.0024). Heavy drinking with psychiatric comorbidities: OR = 0.62 (95% CI 0.45-0.85, p = 0.0031). NAFLD: beta = -0.34 (p = 0.0000274). No significant effects on tobacco, cannabis, or opioid use.","methodology":"Drug-target Mendelian randomization using genetic variants at GLP1R and GIPR loci. Multi-ancestry analysis. Multiple MR methods and colocalization analyses for robustness. Mediation analysis for cardiovascular effects.","limitations":"Genetic proxies simulate lifetime exposure, not short-term drug treatment. Cannot determine optimal dose or duration. Population-level estimates may not apply to individual patients. Observational genetic design cannot fully prove causation."},{"rthcId":"RPEP-13236","title":"Effects from treating moderate- to high-risk obesity patients with anti-obesity medication from a societal perspective.","authors":"Reitzinger, Stephanie; Czypionka, Thomas","year":2025,"journal":"Scientific reports, 15(1), 12959","doi":"10.1038/s41598-025-97472-8","pmid":"40234554","tags":["semaglutide","glp-1-receptor-agonists","obesity-treatment","health-economics"],"studyType":"cost-effectiveness","evidenceStrength":"moderate","keyFinding":"Treating 50% of people with class II and III obesity with semaglutide plus lifestyle changes could cut the prevalence of severe obesity nearly in half and reduce obesity-related costs by about 13% per year in Austria.","whyItMatters":"Obesity medications are expensive, but this analysis suggests they could pay for themselves through reduced healthcare costs and lost productivity. Over a lifetime, moving someone from class III to class II obesity cuts per-patient costs by about 40%.","specificNumbers":"50% treatment of class II/III obesity over 68 weeks. Class II prevalence: 4% to 2.74%. Class III: 1.45% to 0.97%. Annual savings: 108.7 million euros (12.9% reduction). Lifetime cost reduction: about 40% per patient per class shift.","methodology":"Population-attributable fraction approach using Austrian Health Interview Survey 2019 (n = 15,461). Applied semaglutide weight reduction data from clinical trials. Life-cycle cost model comparing obesity classes.","limitations":"Modeled analysis, not observed outcomes. Assumes 68-week treatment adherence. Excludes diabetes patients. Based on Austrian cost data, may not generalize. Does not account for weight regain after stopping treatment. Drug costs included but long-term pricing uncertain."},{"rthcId":"RPEP-13237","title":"Amylin receptors as therapeutic targets in obesity: Emerging peptide-based strategies.","authors":"Rejili, Mokhtar; Hussain, Md Sadique; Khan, Yumna; Haouala, Faouzi; Ganesan, Subbulakshmi; Sahoo, Samir; Pal, Amrita; Arora, Vimal","year":2025,"journal":"Vascular pharmacology, 162, 107563","doi":"10.1016/j.vph.2025.107563","pmid":"41344603","tags":["amylin-and-pramlintide","glp-1-receptor-agonists","obesity-treatment","drug-development-pipeline"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Amylin receptor agonists like cagrilintide and dual-action compounds show strong potential for obesity treatment, especially when combined with GLP-1 receptor agonists, by targeting both homeostatic and reward-driven eating pathways.","whyItMatters":"GLP-1 drugs alone produce meaningful but limited weight loss. Adding amylin-based drugs could push results further by targeting a different hormone system that controls hunger, stomach emptying, and food reward.","specificNumbers":"Not specified in abstract. References pramlintide, cagrilintide, KBP-series DACRAs, ZP8396, and amycretin.","methodology":"Narrative review of preclinical and clinical evidence on amylin receptor agonists for obesity. Covers molecular pharmacology, clinical development, genetic variants, and combination strategies.","limitations":"Narrative review without systematic search or meta-analysis. Most amylin-based agents are still investigational. Long-term efficacy and safety data are limited. Disease-modifying effects beyond weight loss remain unproven."},{"rthcId":"RPEP-13238","title":"The di-leucine motif in the host defense peptide LL-37 is essential for initiation of autophagy in human macrophages.","authors":"Rekha, Rokeya Sultana; Padhi, Avinash; Frengen, Nicolai; Hauenstein, Julia; Végvári, Ákos; Agerberth, Birgitta; Månsson, Robert; Guðmundsson, Guðmundur H; Bergman, Peter","year":2025,"journal":"Cell reports, 44(1), 115031","doi":"10.1016/j.celrep.2024.115031","pmid":"39708316","tags":["antimicrobial-peptides","immune-modulation","preclinical-research"],"studyType":"laboratory","evidenceStrength":"low-moderate","keyFinding":"The antimicrobial peptide LL-37 needs an intact di-leucine motif at its N-terminus to trigger autophagy in macrophages. Chemical modifications like formylation and acetylation block this ability.","whyItMatters":"Autophagy is a key immune defense where cells digest invading bacteria. Understanding how LL-37 activates this process, and why neutrophil-released LL-37 cannot, reveals a new way the immune system regulates infection response.","specificNumbers":"LL-37 truncated or substituted at N-terminal di-leucine failed to initiate autophagy. Formylated and acetylated LL-37 also failed. Macrophages lacking dipeptidyl peptidase-1 did not respond to native LL-37.","methodology":"Cell biology experiments using human macrophages and neutrophils. Mass spectrometry to identify post-translational modifications. Truncated and substituted peptide variants tested. Genetic inactivation of dipeptidyl peptidase-1.","limitations":"In vitro cell culture study. Does not demonstrate in vivo relevance. Single peptide studied. Functional consequences of blocked autophagy on infection outcomes not tested."},{"rthcId":"RPEP-13239","title":"Transcoronary study of biomarkers in patients with heart failure: Insights into intracardiac production.","authors":"Ren, Jie; Zhao, Junhan; Yang, Shengwen; An, Shuoyan; Cai, Chi; Wang, Jing; Gu, Min; Niu, Hongxia; Li, Shurong; Hua, Wei; Gao, Beiyao","year":2025,"journal":"ESC heart failure, 12(3), 1640-1651","doi":"10.1002/ehf2.15175","pmid":"39728840","tags":["natriuretic-peptides","cardiovascular-outcomes","heart-failure","biomarkers-and-diagnostics"],"studyType":"observational","evidenceStrength":"low-moderate","keyFinding":"BNP, galectin-3, and TIMP-1 showed significant increases across the heart in heart failure patients, confirming these three biomarkers are actually produced by cardiac tissue rather than just passively elevated in the blood.","whyItMatters":"Many biomarkers used to diagnose heart failure rise in the blood but may come from other organs. Proving that BNP, galectin-3, and TIMP-1 are made inside the heart strengthens their value as heart-specific diagnostic tools.","specificNumbers":"30 HF patients and 10 controls. BNP: arterial 841.5 vs. coronary sinus 1132.0 ng/mL (p = 0.005). Gal-3: 9.5 vs. 19.7 ng/mL (p = 0.002). TIMP-1: 286.7 vs. 377.3 ng/mL (p = 0.001).","methodology":"Transcoronary gradient study comparing femoral artery and coronary sinus blood samples. Supplemented with canine heart failure model using qPCR and western blot for cardiac tissue expression.","limitations":"Small sample (30 patients, 10 controls). Single time point measurement. Heart failure severity and etiology varied. Animal model may not fully reflect human cardiac biology."},{"rthcId":"RPEP-13240","title":"Efficacy of Hypoglycemic Agents in Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD): A Systematic Review and Network Meta-Analysis.","authors":"Ren, Qiao; Tan, Yao; Zhang, Guixiang; Dai, Yuzhao; Yang, Lidan; Wu, Yunmo; He, He; Chen, Jie","year":2025,"journal":"Journal of evidence-based medicine, 18(2), e70021","doi":"10.1111/jebm.70021","pmid":"40229658","tags":["liraglutide","glp-1-receptor-agonists","liver-disease","type-2-diabetes"],"studyType":"meta-analysis","evidenceStrength":"moderate-high","keyFinding":"Among 26 diabetes medications tested for fatty liver disease, liraglutide was most effective for reducing weight, BMI, and waist circumference, while empagliflozin best reduced liver stiffness. Both drug classes improved liver enzymes and insulin resistance.","whyItMatters":"Fatty liver disease and diabetes often occur together but have no single optimal treatment. This analysis helps rank which drugs work best for specific liver and metabolic targets.","specificNumbers":"37 studies, 2,406 participants, 26 agents compared. Liraglutide most effective for BMI and weight. Empagliflozin most effective for liver stiffness measurement. Both improved ALT, AST, GGT, FPG, and HOMA-IR.","methodology":"Network meta-analysis using Bayesian methods. Searched Chinese and English databases through December 2024. Compared 26 hypoglycemic agents for MASLD treatment across multiple outcomes.","limitations":"Moderate sample sizes per comparison. Bayesian network approach relies on indirect comparisons. Inflammatory and fibrosis outcomes showed minimal change. Not all agents had head-to-head comparisons."},{"rthcId":"RPEP-13241","title":"Comparative in vitro intestinal transport and bioactivity of peptides from wet- and dry-heated goat milk proteins after simulated infant digestion.","authors":"Ren, Qing; Ma, Xuchuan; Keijzer, Paula; Bastiaan-Net, Shanna; Wichers, Harry J; Hettinga, Kasper A","year":2025,"journal":"Food chemistry, 495(Pt 2), 146326","doi":"10.1016/j.foodchem.2025.146326","pmid":"40997423","tags":["bioactive-peptides","preclinical-research","peptide-absorption-and-bioavailability"],"studyType":"laboratory","evidenceStrength":"low","keyFinding":"Heat treatment of goat milk affected which bioactive peptides survived digestion and crossed the intestinal barrier. Dry heating reduced transport of glycated peptides and altered the bioactive peptide profile reaching the bloodstream side.","whyItMatters":"How infant formula is processed changes which health-active peptides a baby absorbs. This matters for designing formulas that deliver the right peptides for immune and developmental benefits.","specificNumbers":"Protein concentration 12 mg/mL. Casein-to-whey ratios of 80:20 and 40:60 tested. Peptide transport assessed across Caco-2 cell monolayers.","methodology":"In vitro simulated infant digestion followed by peptide transport across Caco-2 cell monolayers. Compared dry-heated, wet-heated, and unheated goat milk samples. Peptide identification by mass spectrometry.","limitations":"In vitro model does not fully replicate infant gut physiology. Caco-2 cells are derived from adult colon cancer, not infant intestine. No in vivo validation. Single protein source (goat milk)."},{"rthcId":"RPEP-13242","title":"Effects of dry heating on the cleavage of casein and whey protein into peptides under simulated infant digestion.","authors":"Ren, Qing; Ma, Xuchuan; Boeren, Sjef; Keijzer, Paula; Wichers, Harry J; Hettinga, Kasper A","year":2025,"journal":"Food chemistry, 468, 142397","doi":"10.1016/j.foodchem.2024.142397","pmid":"39671917","tags":["bioactive-peptides","preclinical-research","peptide-absorption-and-bioavailability"],"studyType":"laboratory","evidenceStrength":"low","keyFinding":"Dry heating of goat milk proteins altered peptide formation during simulated infant digestion. Casein peptides became longer and less effectively cleaved, while whey protein peptides became shorter, changing the predicted bioactivity profile.","whyItMatters":"Processing conditions during formula manufacturing change what peptides form during a baby's digestion. These changes could affect the health benefits or risks of the formula.","specificNumbers":"40% casein, 60% whey protein model. 72-hour dry heating significantly decreased total intensity and number of whey protein-derived peptides.","methodology":"Simulated infant digestion of heated and unheated goat protein model system. Peptide identification and quantification by mass spectrometry. Bioactivity prediction for identified peptides.","limitations":"In vitro digestion model, not tested in infants. Single protein model system (40:60 casein:whey). Predicted bioactivity may not reflect actual in vivo effects. No functional assays performed."},{"rthcId":"RPEP-13243","title":"Semaglutide Therapy and Accelerated Sarcopenia in Older Adults with Type 2 Diabetes: A 24-Month Retrospective Cohort Study.","authors":"Ren, Qingjuan; Zhi, Lei; Liu, Hongfang","year":2025,"journal":"Drug design, development and therapy, 19, 5645-5652","doi":"10.2147/DDDT.S531778","pmid":"40631351","tags":["semaglutide","glp-1-receptor-agonists","type-2-diabetes","aging-and-peptides","safety-and-side-effects"],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"Semaglutide treatment over 24 months reduced both BMI and muscle mass in older adults with type 2 diabetes. Grip strength initially improved then declined in men, while gait speed decreased in both sexes. Higher doses predicted greater muscle loss.","whyItMatters":"Older adults with diabetes are already at risk for muscle wasting. Semaglutide accelerates this loss, especially at higher doses. Doctors need to monitor muscle mass and function in elderly patients on this drug.","specificNumbers":"220 semaglutide patients, 212 controls. Sarcopenia prevalence 27.7%. Significant reductions in BMI and ASMI in semaglutide group. Gait speed reduced in both sexes. Semaglutide dose, baseline ASMI, and gait speed were independent predictors of muscle loss.","methodology":"Retrospective cohort study comparing semaglutide-treated elderly T2DM patients to matched controls. Measured ASMI, grip strength, and gait speed over 24 months. Multivariable linear regression for predictors.","limitations":"Retrospective design. No randomization. Potential confounding by indication (sicker patients may be prescribed semaglutide). No dietary or exercise data collected. Single-center study."},{"rthcId":"RPEP-13244","title":"The effect of semaglutide combined with metformin on liver inflammation and pancreatic beta-cell function in patients with type 2 diabetes and non-alcoholic fatty liver disease.","authors":"Ren, Rong; Pei, Yanxia; Kong, Lufei; Shi, Yixin","year":2025,"journal":"Journal of diabetes and its complications, 39(2), 108932","doi":"10.1016/j.jdiacomp.2024.108932","pmid":"39700591","tags":["semaglutide","glp-1-receptor-agonists","liver-disease","type-2-diabetes","beta-cell-function"],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"Adding semaglutide to metformin significantly improved liver inflammation markers, reduced fibrosis scores, and enhanced pancreatic beta cell function compared to metformin alone in patients with type 2 diabetes and fatty liver disease.","whyItMatters":"Many people with type 2 diabetes also have fatty liver disease. This study shows semaglutide adds meaningful liver and pancreas benefits on top of standard metformin therapy.","specificNumbers":"261 patients (134 semaglutide+metformin, 127 metformin alone). ALT: 23.59 vs 25.56 U/L. AST: 18.97 vs 20.15 U/L. FIB-4: 1.05 vs 1.16. Matsuda index: 5.18 vs 4.84. DIo: 0.18 vs 0.16.","methodology":"Retrospective study at a single institution. Patients treated January 2021 to December 2023. Compared liver enzymes, FIB-4 fibrosis index, and beta cell function measures between groups.","limitations":"Retrospective, non-randomized design. Single center. Relatively small differences in some markers. No liver biopsy or imaging confirmation. Selection bias possible between treatment groups."},{"rthcId":"RPEP-13245","title":"Impaired meningeal lymphatic drainage correlates with headache intensity in episodic migraine.","authors":"Ren, Xiao; Wang, Han; He, Yali; Wu, Chengsi; Chen, Kaixiao; Zhou, Fuqing; Xiao, Zhihua; Liu, Yi; Wang, Yonggang; Hong, Daojun","year":2025,"journal":"The journal of headache and pain, 26(1), 265","doi":"10.1186/s10194-025-02211-z","pmid":"41266984","tags":["cgrp-peptides","migraine","neurological-applications"],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"Episodic migraine patients showed impaired meningeal lymphatic drainage on dynamic MRI, and the degree of impairment correlated with headache intensity.","whyItMatters":"The glymphatic system clears waste from the brain. If this system is impaired in migraine, it could explain why attacks persist and worsen. Meningeal lymphatic vessels could become a new treatment target.","specificNumbers":"38 episodic migraine patients and 22 controls. Reduced wash-in rate, prolonged time-to-peak, and lower IAUC and Ktrans in both mLV-SSS and mLV-SS regions. Kinetic abnormalities correlated with VAS headache scores.","methodology":"Prospective case-control study using 3T MRI. Dynamic contrast-enhanced MRI for meningeal lymphatic kinetics. DTI-ALPS index for parenchymal fluid dynamics. Structural MRI for enlarged perivascular spaces.","limitations":"Small sample size (38 patients). Cross-sectional design. DTI-ALPS index showed no group difference. Cannot determine if drainage impairment causes migraine or results from it."},{"rthcId":"RPEP-13246","title":"Efficacy and safety of GLP-1 agonists in the treatment of T2DM: A systematic review and network meta-analysis.","authors":"Ren, Xiaoyu; Hua, Honghao; Wu, Yuanqin; Zhang, Wei; Long, Xianzhen; Bai, Yana; Cheng, Ning","year":2025,"journal":"Scientific reports, 15(1), 24103","doi":"10.1038/s41598-025-09807-0","pmid":"40619508","tags":["glp-1-receptor-agonists","tirzepatide","semaglutide","liraglutide","type-2-diabetes"],"studyType":"meta-analysis","evidenceStrength":"high","keyFinding":"In 64 trials with 25,572 patients, tirzepatide produced the greatest HbA1c reduction (-2.3%) and weight loss (-9.1 kg) among GLP-1 receptor agonists for type 2 diabetes.","whyItMatters":"This is the largest network comparison of GLP-1 drugs for diabetes. Tirzepatide clearly outperformed semaglutide and liraglutide for blood sugar and weight.","specificNumbers":"64 trials, 25,572 participants. Tirzepatide: HbA1c -2.3%, FPG -3.1 mmol/L, weight -9.1 kg. Semaglutide: HbA1c -1.5%, FPG -2 mmol/L, weight -2.8 kg. Liraglutide: HbA1c -1.2%, FPG -1.6 mmol/L, weight -1.2 kg.","methodology":"Systematic review and Bayesian network meta-analysis. Searched databases through October 2024. Included RCTs comparing GLP-1 RAs for T2DM.","limitations":"Relies partly on indirect comparisons. No significant differences for BMI, blood pressure, or cholesterol between agents. Heterogeneity in trial designs."},{"rthcId":"RPEP-13247","title":"A SynB1-conjugated antibody cocktail crosses the blood-brain barrier to produce a therapeutic effect on rabies.","authors":"Ren, Zeheng; Wang, Caiqian; Wang, Haoran; Wu, Qiong; Hou, Qingxiu; Qi, Xue; He, Wenna; Zhang, Xiaoyu; Wan, Jiawu; Fu, Zhen F; Zhou, Ming; Zhao, Ling","year":2025,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 122(52), e2516465122","doi":"10.1073/pnas.2516465122","pmid":"41433073","tags":["peptide-drug-conjugates","drug-delivery-systems","preclinical-research","blood-brain-barrier"],"studyType":"preclinical","evidenceStrength":"low-moderate","keyFinding":"The cell-penetrating peptide SynB1, conjugated to rabies antibodies, enabled blood-brain barrier crossing and rescued 80% of mice from lethal rabies even after symptom onset.","whyItMatters":"Rabies is nearly 100% fatal once symptoms begin because antibodies cannot reach the brain. This peptide-antibody conjugate is the first to show post-symptom rescue in an animal model.","specificNumbers":"80% survival with SynB1 cocktail vs. 20% (CVS) or 0% (DRV) unconjugated. Treatment at 5 days post-infection. Four peptides tested; SynB1 best.","methodology":"Generated chimeric antibodies targeting RABV-G epitopes II/III/IV. Conjugated to four cell-penetrating peptides. In vivo fluorescence imaging and lethal challenge in mice.","limitations":"Mouse model only. Lab virus strains may differ from wild-type. No human safety data. Manufacturing complexity of peptide-antibody conjugates."},{"rthcId":"RPEP-13248","title":"Cost-Effectiveness of Semaglutide in Patients With Obesity and Cardiovascular Disease.","authors":"Rennert-May, Elissa; Manns, Braden; Clement, Fiona; Spackman, Eldon; Collister, David; Sumner, Glen; Leal, Jenine; Miller, Robert J H; Chew, Derek S","year":2025,"journal":"The Canadian journal of cardiology, 41(1), 128-136","doi":"10.1016/j.cjca.2024.09.025","pmid":"39772331","tags":["semaglutide","glp-1-receptor-agonists","cardiovascular-outcomes","health-economics"],"studyType":"cost-effectiveness","evidenceStrength":"moderate","keyFinding":"Semaglutide for obese cardiovascular patients without diabetes cost $72,962 per QALY in Canada. At a 50% price cut, it became cost-effective at $37,190 per QALY.","whyItMatters":"Semaglutide reduces heart attacks and strokes in obese patients with heart disease, but current pricing may exceed public health system thresholds. Price negotiations are key.","specificNumbers":"ICER: $72,962/QALY. 14% cost-effective at $50K threshold. At 50% price cut: $37,190/QALY with 80% probability. Semaglutide 2.4 mg weekly. 2023 CAD$.","methodology":"Decision analytic Markov model. Lifetime horizon, monthly cycles. Healthcare payer perspective. Modeled stroke, HF, MI, death. Sensitivity analysis.","limitations":"Modeled analysis from SELECT trial. Canadian pricing only. Assumes sustained benefit. Does not model weight regain or budget impact."},{"rthcId":"RPEP-13249","title":"Cyclic peptide structure prediction and design using AlphaFold2.","authors":"Rettie, Stephen A; Campbell, Katelyn V; Bera, Asim K; Kang, Alex; Kozlov, Simon; Bueso, Yensi Flores; De La Cruz, Joshmyn; Ahlrichs, Maggie; Cheng, Suna; Gerben, Stacey R; Lamb, Mila; Murray, Analisa; Adebomi, Victor; Zhou, Guangfeng; DiMaio, Frank; Ovchinnikov, Sergey; Bhardwaj, Gaurav","year":2025,"journal":"Nature communications, 16(1), 4730","doi":"10.1038/s41467-025-59940-7","pmid":"40399308","tags":["peptide-engineering","drug-development-pipeline","computational-peptide-design"],"studyType":"computational","evidenceStrength":"low-moderate","keyFinding":"AlphaFold2 was adapted to predict and design cyclic peptide structures. Over 10,000 designs were generated, with 8 tested sequences matching predictions closely and some binding targets with nanomolar affinity.","whyItMatters":"Designing cyclic peptides has been limited by lack of deep learning tools. This method enables rapid computational design of therapeutic peptide candidates.","specificNumbers":"Over 10,000 designs. 8 tested matched X-ray structures (RMSD under 1 angstrom). IC50 under 50 nM against MDM2 and Keap1.","methodology":"Deep learning approach adapting AlphaFold2 for cyclic peptides. Structure prediction, sequence redesign, and de novo hallucination. X-ray crystallography and binding assay validation.","limitations":"Only 8 of 10,000+ designs experimentally tested. Two targets only. In vitro binding does not guarantee in vivo efficacy."},{"rthcId":"RPEP-13250","title":"Clinical Effectiveness of Oral Semaglutide in Women with Type 2 Diabetes: A Nationwide, Multicentre, Retrospective, Observational Study (Women_ENDO2S-RWD Substudy).","authors":"Reyes-Garcia, Rebeca; Moreno-Pérez, Oscar; Guillen-Morote, Cristina; Modrego-Pardo, Inés; Doulatram-Gamgaram, Viyey Kishore; Casado Cases, Carlos; Arias Mendoza, Nieves; Tejera-Pérez, Cristina; Cárdenas-Salas, Jersy; Martínez-Fuster, Sandra; Lardiés-Sánchez, Beatriz; Márquez-Pardo, Rosa; Pinés, Pedro; Tejera-Muñoz, Antonio; Fernández-García, José Carlos; On Behalf Of The Seen Diabetes Area","year":2025,"journal":"Nutrients, 17(14)","doi":"10.3390/nu17142349","pmid":"40732973","tags":["semaglutide","glp-1-receptor-agonists","oral-peptide-delivery","type-2-diabetes","real-world-evidence"],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"Oral semaglutide worked equally well in women and men with type 2 diabetes in real-world practice. Women lost 7.2% body weight at 12 months, with nearly 30% losing more than 10%.","whyItMatters":"This large real-world study confirms oral semaglutide is equally effective and safe in women with type 2 diabetes, filling a gap in sex-specific evidence.","specificNumbers":"1,018 patients (469 women). At 12 months: HbA1c -0.9%, weight -7.2%, 29.8% lost over 10%, 59.3% reached HbA1c target, 76.3% persistence. No sex differences.","methodology":"Nationwide multicenter retrospective observational study in Italy. Patients started oral semaglutide Nov 2021-Nov 2022 with at least 3-month follow-up.","limitations":"Retrospective. Italian population. No randomization. Self-selection bias in persistent patients."},{"rthcId":"RPEP-13251","title":"Development of nebulized inhalation delivery for fusion-inhibitory lipopeptides to protect non-human primates against Nipah-Bangladesh infection.","authors":"Reynard, Olivier; Iampietro, Mathieu; Dumont, Claire; Le Guellec, Sandrine; Durand, Stephanie; Moroso, Marie; Brisebard, Elise; Dhondt, Kévin P; Pelissier, Rodolphe; Mathieu, Cyrille; Cabrera, Maria; Le Pennec, Deborah; Amurri, Lucia; Alabi, Christopher; Cardinaud, Sylvain; Porotto, Matteo; Moscona, Anne; Vecellio, Laurent; Horvat, Branka","year":2025,"journal":"Antiviral research, 235, 106095","doi":"10.1016/j.antiviral.2025.106095","pmid":"39870114","tags":["antimicrobial-peptides","drug-delivery-systems","preclinical-research"],"studyType":"preclinical","evidenceStrength":"low","keyFinding":"A nebulized lipopeptide fusion inhibitor delivered to monkey lungs was safe and protected 2 of 5 monkeys from lethal Nipah virus infection, with all treated animals showing delayed disease and preserved immune cells.","whyItMatters":"Nipah virus has no approved treatment or vaccine and kills up to 75% of those infected. An inhaled antiviral peptide that can be given quickly after exposure could fill a critical gap in pandemic preparedness.","specificNumbers":"3 nebulized doses every 24 hours. Peptide deposited across multiple lung regions. 2 of 5 treated monkeys survived lethal NiV-Bangladesh challenge. No toxicity or adverse hematological/biochemical effects.","methodology":"Aerosol delivery optimization using 3D respiratory model. Safety assessment in African green monkeys. Lethal Nipah-Bangladesh challenge study with peptide-treated vs. control monkeys.","limitations":"Only 2 of 5 monkeys fully protected. Small sample typical of BSL-4 primate studies. First-generation lipopeptide; next-generation versions being developed. Prophylactic dosing only, not post-exposure treatment."},{"rthcId":"RPEP-13252","title":"The effects of collagen peptide supplementation on appetite and post-exercise energy intake in females: a randomised controlled trial.","authors":"Reynolds, Kirsty M; Hansell, Emily J; Thorley, Josh; Funnell, Mark P; Thackray, Alice E; Stensel, David J; Bailey, Stephen J; James, Lewis J; Prawitt, Janne; Virgilio, Nicolina; Clifford, Tom","year":2025,"journal":"The British journal of nutrition, 134(4), 265-276","doi":"10.1017/S0007114525103851","pmid":"40685650","tags":["bioactive-peptides","glp-1-receptor-agonists","weight-management"],"studyType":"clinical-trial","evidenceStrength":"low-moderate","keyFinding":"Collagen peptide supplementation after exercise increased GLP-1 levels and reduced food intake by about 10% at a subsequent meal in active women, suggesting collagen peptides stimulate satiety hormones.","whyItMatters":"Collagen peptides are widely used supplements. This study shows they may influence appetite-regulating hormones like GLP-1, potentially helping with post-exercise appetite control.","specificNumbers":"15 women, 23 years old average. 15 g/day collagen peptides for 7 days. Post-exercise energy intake about 10% lower (41 kcal). GLP-1 AUC: 9064 vs 6369 pmol/L (p < 0.05). Ghrelin decreased, insulin increased.","methodology":"Randomized, double-blind, crossover study. 7-day supplementation periods. Exercise at 55% Wmax for 45 min. Ad libitum meal 60 min post-supplement. Blood hormones measured at multiple timepoints.","limitations":"Very small sample (15 women). Only one exercise session measured. Short supplementation period. 41 kcal difference is small and may not be clinically meaningful. Women only, results may not apply to men."},{"rthcId":"RPEP-13253","title":"Unveiling the Promising Role of Substance P/Neurokinin 1 Receptor in Cancer Cell Proliferation and Cell Cycle Regulation in Human Malignancies.","authors":"Rezaei, Soodabeh; Javid, Hossein; Iranpour, Sonia; Darban, Reza Assaran; Hashemy, Seyed Isaac","year":2025,"journal":"Current medicinal chemistry, 32(27), 5716-5732","doi":"10.2174/0109298673311337240702095139","pmid":"38988156","tags":["neuropeptides","substance-p-and-neurokinins","cancer-applications"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"The substance P/neurokinin-1 receptor pathway regulates cell proliferation and cell cycle genes across many human cancers. NK1R antagonists show promising anticancer effects in early research.","whyItMatters":"Substance P, a neuropeptide best known for pain signaling, also drives cancer cell growth. Blocking its receptor with NK1R antagonists could become a new approach to cancer treatment.","specificNumbers":"Not specified. Reviews evidence across multiple cancer types and NK1R antagonist studies.","methodology":"Comprehensive narrative review of SP/NK1R signaling in cancer biology. Covers receptor pharmacology, cell cycle regulation, oncogene interactions, and NK1R antagonist research.","limitations":"Narrative review without systematic search or meta-analysis. Most NK1R antagonist data from preclinical studies. Clinical translation remains early-stage."},{"rthcId":"RPEP-13254","title":"The binding mechanism of Covalent Organic Frameworks (COFs) to Calcitonin Gene-Related Peptide Receptors (CGRPRs).","authors":"Rezvantalab, Sima; Imanpour, Aylar; Dabiri, Mohammad; Beheshtizadeh, Nima","year":2025,"journal":"International journal of biological macromolecules, 322(Pt 4), 147038","doi":"10.1016/j.ijbiomac.2025.147038","pmid":"40848802","tags":["cgrp-peptides","cgrp-receptor-antagonists","computational-peptide-design","migraine"],"studyType":"computational","evidenceStrength":"low","keyFinding":"Molecular dynamics simulations showed that certain covalent organic frameworks can bind directly to the CGRP receptor complex, potentially acting as macromolecular antagonists rather than just drug carriers.","whyItMatters":"Covalent organic frameworks have been seen only as drug delivery vehicles. This study suggests some may directly block the CGRP receptor, opening a new category of antimigraine materials.","specificNumbers":"3 COF models tested (TPE-COF, 3D-Py-COF, 4PE-1P-COF). Compared to ubrogepant and rimegepant as controls. Molecular dynamics and docking simulations used.","methodology":"Molecular dynamics and docking simulations to model COF binding to CLR/RAMP1 complex. Used antimigraine drugs ubrogepant and rimegepant as reference compounds.","limitations":"Entirely computational. No experimental validation. COF biocompatibility, pharmacokinetics, and toxicity unknown. Translation from simulation to clinical use would require extensive testing."},{"rthcId":"RPEP-13255","title":"The intricate relationship between circadian rhythms and gastrointestinal peptides in obesity.","authors":"Ribeiro, Filipe M; Arnaldo, Luiz; P Milhomem, Lana; S Aguiar, Samuel; Franco, Octavio L","year":2025,"journal":"Peptides, 185, 171356","doi":"10.1016/j.peptides.2025.171356","pmid":"39929256","tags":["glp-1-receptor-agonists","neuropeptides","obesity-treatment","gut-peptides"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Circadian rhythm disruptions alter the secretion of appetite-regulating gut peptides like GLP-1 and PYY, contributing to overeating and metabolic dysfunction in obesity.","whyItMatters":"The body's internal clock controls when hunger hormones are released. When this clock is disrupted by shift work, irregular meals, or poor sleep, appetite regulation breaks down. This connection could open new treatment strategies for obesity.","specificNumbers":"Not specified. Reviews molecular pathways linking CLOCK/BMAL1, REV-ERBa/RORa to GLP-1 and PYY regulation.","methodology":"Narrative review of molecular pathways linking circadian rhythms, hypothalamic peptides, and gastrointestinal peptide secretion in obesity.","limitations":"Narrative review. Clinical studies linking circadian peptide regulation to obesity treatment are scarce. Mechanistic pathways largely from animal models."},{"rthcId":"RPEP-13256","title":"In vitro strategies to understand the impact of oral intake on the bioavailability and bioactivity of peptides from brewing by-products.","authors":"Ribeiro-Oliveira, Rita; Diniz, Carmen; Ferreira, Isabel M P L V O","year":2025,"journal":"Critical reviews in food science and nutrition, 65(17), 3282-3290","doi":"10.1080/10408398.2024.2362410","pmid":"38950579","tags":["bioactive-peptides","peptide-absorption-and-bioavailability"],"studyType":"review","evidenceStrength":"low-moderate","keyFinding":"Bioactive peptides from brewing by-products lose significant activity during digestion, intestinal absorption, and liver metabolism. The biggest knowledge gap is the impact of hepatic metabolism on these peptides.","whyItMatters":"Brewing waste contains peptides with potential health benefits, but what survives digestion and reaches the bloodstream may not work as well as lab tests suggest. Understanding these losses is critical before marketing such products.","specificNumbers":"Not specified. Reviews multiple in vitro studies of brewing-derived peptide bioavailability.","methodology":"Critical narrative review of in vitro studies assessing gastrointestinal digestion, intestinal absorption, and hepatic metabolism effects on brewer's spent grain and yeast peptides.","limitations":"Based entirely on in vitro evidence. No clinical studies reviewed. In vitro models may not accurately reflect human physiology. Limited studies on hepatic metabolism."},{"rthcId":"RPEP-13257","title":"Toward effective oxytocin interventions in autism: Overcoming challenges and harnessing opportunities.","authors":"Ricchiuti, Grazia; Tuerlinckx, Elise; Taillieu, Aymara; Prinsen, Jellina; Steyaert, Jean; Boets, Bart; Alaerts, Kaat","year":2025,"journal":"Journal of psychopharmacology (Oxford, England), 39(3), 179-186","doi":"10.1177/02698811241309621","pmid":"39861928","tags":["oxytocin","neurological-applications","neuropeptides"],"studyType":"review","evidenceStrength":"low-moderate","keyFinding":"Intranasal oxytocin for autism shows mixed results. Optimal protocols appear to favor moderate durations (4-6 weeks), intermittent dosing (24-32 IU every other day), and pairing with socially stimulating environments.","whyItMatters":"Oxytocin has been a promising but frustrating autism treatment. This review identifies specific reasons trials have failed and suggests concrete design improvements that could unlock the peptide's potential.","specificNumbers":"Optimal dosing: 24-32 IU every other day. Optimal duration: 4-6 weeks. Enhanced outcomes when paired with socially stimulating environments.","methodology":"Perspective/review analyzing factors contributing to variability in oxytocin trial results for autism. Covers design elements and individual characteristics.","limitations":"Not a systematic review or meta-analysis. Recommended protocols based on pattern analysis of mixed results rather than definitive evidence. Small sample sizes in most referenced trials."},{"rthcId":"RPEP-13258","title":"Cardiovascular Disease and Diabetes: A New Challenge in the Treatment and Management.","authors":"Riccioni, Graziano; Notarangelo, Chiara; Riccioni, Mario; D'Orazio, Nicolantonio","year":2025,"journal":"International journal of molecular sciences, 27(1)","doi":"10.3390/ijms27010354","pmid":"41516231","tags":["glp-1-receptor-agonists","semaglutide","liraglutide","cardiovascular-outcomes","type-2-diabetes"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Newer diabetes drugs including GLP-1 receptor agonists, DPP4 inhibitors, and SGLT-2 inhibitors match older drugs for blood sugar control while providing superior cardiovascular safety and reduced mortality.","whyItMatters":"Diabetes patients face high cardiovascular risk. Having drugs that control blood sugar and protect the heart simultaneously is a major advance over older therapies that only addressed glucose.","specificNumbers":"Not specified in abstract. Reviews cardiovascular outcome trial data for multiple agents.","methodology":"Narrative review of cardiovascular safety and efficacy data for DPP4 inhibitors, GLP-1 RAs, and SGLT-2 inhibitors in diabetes.","limitations":"Narrative review. Does not provide pooled quantitative analysis. May not capture all newer trial results."},{"rthcId":"RPEP-13259","title":"Investigating How Lysophosphatidylcholine and Lysophosphatidylethanolamine Enhance the Membrane Permeabilization Efficacy of Host Defense Peptide Piscidin 1.","authors":"Rice, Amy; Zourou, Andriana C; Goodell, Evan P; Fu, Riqiang; Pastor, Richard W; Cotten, Myriam L","year":2025,"journal":"The journal of physical chemistry. B, 129(1), 210-227","doi":"10.1021/acs.jpcb.4c05845","pmid":"39681296","tags":["antimicrobial-peptides","preclinical-research"],"studyType":"laboratory","evidenceStrength":"low","keyFinding":"Lysophospholipids boost the membrane-disrupting ability of the host defense peptide piscidin 1 without changing its binding or shape. LPC enhanced permeabilization more than LPE.","whyItMatters":"In real infections, antimicrobial peptides work alongside other membrane-active molecules. Understanding how they cooperate could improve the design of peptide-based antibiotics.","specificNumbers":"Efficacy order: POPC/POPG/LPC > POPE/POPG/LPE > POPC/POPG > POPE/POPG. Four membrane systems tested. MD simulations over nanosecond timescales.","methodology":"Combined dye leakage assays, circular dichroism, NMR spectroscopy, and molecular dynamics simulations across four membrane compositions.","limitations":"Model membrane systems, not real bacterial membranes. Single peptide tested. In vitro/computational only. No antimicrobial activity assays against live bacteria."},{"rthcId":"RPEP-13260","title":"A Remotely Delivered GLP-1RA-Supported Specialist Weight Management Program in Adults Living With Obesity: Retrospective Service Evaluation.","authors":"Richards, Rebecca; Whitman, Michael; Wren, Gina; Campion, Peta","year":2025,"journal":"JMIR formative research, 9, e72577","doi":"10.2196/72577","pmid":"40434299","tags":["semaglutide","glp-1-receptor-agonists","obesity-treatment","real-world-evidence","weight-management"],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"A remote semaglutide-supported weight program achieved 19.1% weight loss in active subscribers at 12 months, with 78% losing 10%+ and 62% losing 15%+. However, 60% of participants became inactive.","whyItMatters":"While completers achieved impressive results comparable to clinical trials, the 60% dropout rate shows that engagement is the biggest challenge for remote obesity programs, even with effective medication.","specificNumbers":"341 baseline participants (82.7% women, mean BMI 37.9). Active at 12 months: 39.6%. Active subscribers: -20.0 kg (-19.1%). 77.7% lost 10%+, 61.5% lost 15%+. 69.6% reported no side effects by month 12.","methodology":"Retrospective service evaluation of a commercial remote weight program (Second Nature). Participants started Sept-Dec 2023. Paired t-tests for outcomes. Qualitative experience analysis.","limitations":"60% dropout rate limits generalizability. Weight data available for only 52.5% at 12 months. No intent-to-treat analysis. Single commercial program. UK-specific."},{"rthcId":"RPEP-13261","title":"Semaglutide and Tirzepatide in a Remote Weight Management Program: 12-Month Retrospective Observational Study.","authors":"Richards, Rebecca; Lunt, William; Whitman, Michael; Spaltro, Giulia; Hall, Rachel","year":2025,"journal":"JMIR formative research, 9, e81912","doi":"10.2196/81912","pmid":"40838489","tags":["tirzepatide","semaglutide","glp-1-receptor-agonists","obesity-treatment","real-world-evidence","weight-management"],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"In a 12-month remote weight management program, tirzepatide users lost 22.1% of body weight and semaglutide users lost 17.1%, with 95% and 83% respectively achieving at least 10% weight loss.","whyItMatters":"Remote digital programs combined with GLP-1 drugs can match clinical trial-level weight loss at 60-70% lower cost than specialist services. This could dramatically expand access to effective obesity treatment.","specificNumbers":"339 participants (82% women). Tirzepatide: -22.9 kg (-22.1%), 95.2% lost 10%+, 83.7% lost 15%+. Semaglutide: -18.1 kg (-17.1%), 83.1% lost 10%+, 56.2% lost 15%+. 60-70% cost savings vs. specialist services.","methodology":"Retrospective analysis of participants completing a 12-month remote program (Feb-June 2024). Combined medication, app-based behavioral support, dietitian coaching, and clinical oversight across 5 phases.","limitations":"Retrospective, non-randomized. Completers only (selection bias). No control group without medication. Short follow-up for weight maintenance. UK-specific cost comparisons."},{"rthcId":"RPEP-13262","title":"The influence of the glucagon-like peptide-1 receptor agonist, liraglutide, on dietary patterns and nutrient intakes in patients with obesity and prediabetes: A secondary analysis of a randomized controlled trial.","authors":"Richardson, Kelli M; Schembre, Susan M; Jospe, Michelle R; Widmer, Annaliese; Silver, Heidi J","year":2025,"journal":"Diabetes, obesity & metabolism, 27(7), 3725-3735","doi":"10.1111/dom.16395","pmid":"40259488","tags":["liraglutide","glp-1-receptor-agonists","obesity-treatment","weight-management"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"Liraglutide reduced calorie intake but did not improve overall diet quality compared to dietitian-guided caloric restriction. The caloric restriction group made bigger improvements in protein intake and added sugar reduction.","whyItMatters":"GLP-1 drugs help people eat less, but they do not necessarily help people eat better. Adding nutrition counseling to GLP-1 treatment may be important for long-term health outcomes beyond weight loss.","specificNumbers":"70 participants (69% female, 83% white, mean BMI 39.5). 2:1:1 randomization. Liraglutide 1.8 mg/day for 14 weeks. Significant differences in protein (p=0.037), carbs (p=0.019), and added sugar (p=0.002) changes across groups.","methodology":"Secondary analysis of a randomized controlled trial. 24-hour dietary recall pre- and post-intervention. Compared liraglutide, dietitian-guided caloric restriction (-390 kcal/day), and DPP4 inhibitor (100 mg/day).","limitations":"Small sample (70 patients). Single 24-hour recall may not capture habitual intake. Short duration (14 weeks). Secondary analysis, not powered for dietary outcomes."},{"rthcId":"RPEP-13263","title":"Evidence for independent actions of the CRF and ghrelin systems in binge-like alcohol drinking in mice.","authors":"Richardson, Rani S; Kryszak, Lindsay A; Vendruscolo, Janaina C M; Koob, George F; Leggio, Lorenzo; Vendruscolo, Leandro F","year":2025,"journal":"Progress in neuro-psychopharmacology & biological psychiatry, 138, 111341","doi":"10.1016/j.pnpbp.2025.111341","pmid":"40139339","tags":["neuropeptides","substance-use-and-addiction","preclinical-research","gut-peptides"],"studyType":"preclinical","evidenceStrength":"low","keyFinding":"CRF receptor antagonism and ghrelin receptor blockade both reduced binge-like alcohol drinking in mice, but the two systems acted independently rather than interacting to produce the effect.","whyItMatters":"Both stress hormones (CRF) and hunger hormones (ghrelin) drive alcohol binge drinking. Knowing they work through separate pathways means combining drugs targeting each system might produce additive benefits.","specificNumbers":"R121919 (brain-penetrant CRF1 antagonist) increased plasma ghrelin and reduced binge drinking. Astressin (peripheral CRF antagonist) did neither. No sex-by-treatment interactions observed.","methodology":"Binge-like alcohol drinking model (drinking in the dark) in male and female C57BL/6J mice. Tested CRF antagonists alone and combined with ghrelin receptor antagonists. Measured plasma ghrelin.","limitations":"Mouse model only. Binge drinking model may not reflect human alcohol use disorder. Limited drug combinations tested. No human translation data."},{"rthcId":"RPEP-13264","title":"Docking Simulations of G-Protein Coupled Receptors Uncover Crossover Binding Patterns of Diverse Ligands to Angiotensin, Alpha-Adrenergic and Opioid Receptors: Implications for Cardiovascular Disease and Addiction.","authors":"Ridgway, Harry; Moore, Graham J; Gadanec, Laura Kate; Matsoukas, John M","year":2025,"journal":"Biomolecules, 15(6)","doi":"10.3390/biom15060855","pmid":"40563495","tags":["neuropeptides","computational-peptide-design","substance-use-and-addiction"],"studyType":"computational","evidenceStrength":"low","keyFinding":"Molecular docking showed angiotensin receptor blockers bind to opioid and adrenergic receptors with higher affinity than their native ligands, suggesting potential therapeutic applications in addiction and hypertension.","whyItMatters":"If blood pressure drugs can block opioid receptors, they might help treat opioid addiction. This computational finding needs laboratory confirmation but could repurpose existing medications.","specificNumbers":"ARBs showed higher binding affinity for mu- and delta-opioid receptors than fentanyl and naltrexone. ARBs partially reduced (20-50%) contractile responses to phenylephrine at very low concentrations. MD simulations stable over nanosecond timescales.","methodology":"Virtual ligand screening (docking) and molecular dynamics simulations for ARBs, opioids, and adrenergic ligands at AT1R, alpha-1AR, alpha-2AR, mu-opioid, and delta-opioid receptors.","limitations":"Entirely computational. Binding affinity predictions need experimental confirmation. In silico docking scores do not guarantee functional effects. No in vivo or clinical data."},{"rthcId":"RPEP-13265","title":"The Spectrum of Headaches in Moyamoya Angiopathy: From Mechanisms to Management Strategies-A Consensus Review From the NEUROVASC Working Group.","authors":"Rifino, Nicola; Aamodt, Anne Hege; Wiedmann, Markus; Kramer, Markus; Becker, Jana; Guey, Stéphanie; Acerbi, Francesco; Herve, Dominique; Bersano, Anna","year":2025,"journal":"European journal of neurology, 32(10), e70316","doi":"10.1111/ene.70316","pmid":"41039799","tags":["cgrp-peptides","migraine","cgrp-monoclonal-antibodies","cgrp-receptor-antagonists"],"studyType":"review","evidenceStrength":"low-moderate","keyFinding":"Headache occurs in up to 75% of moyamoya patients, often mimicking migraine. CGRP inhibitors and lasmiditan show potential but lack specific data in this population. Surgical revascularization may reduce headache but results vary.","whyItMatters":"Moyamoya headaches are often mismanaged because they look like migraine but have different underlying causes. Newer migraine drugs like CGRP inhibitors need testing in this vulnerable population.","specificNumbers":"Headache reported in up to 75% of moyamoya patients. No standardized treatment exists.","methodology":"Consensus narrative review from the NEUROVASC Working Group. Literature review of headache prevalence, mechanisms, and treatment in moyamoya angiopathy.","limitations":"Rare disease with very limited evidence. No randomized trials. Recommendations largely empirical. CGRP inhibitor data in moyamoya are theoretical."},{"rthcId":"RPEP-13266","title":"Neuropeptide Y neurons surrounding the locus coeruleus inhibit noradrenergic system activity to reduce anxiety.","authors":"Riga, Danai; Kooij, Karlijn L; Rademakers, Kelly; Wolterink-Donselaar, Inge G; Basak, Onur; Meye, Frank J","year":2025,"journal":"Science advances, 11(30), eadq0011","doi":"10.1126/sciadv.adq0011","pmid":"40700482","tags":["neuropeptides","neuropeptide-y","neurological-applications","preclinical-research"],"studyType":"preclinical","evidenceStrength":"low-moderate","keyFinding":"NPY-expressing neurons surrounding the locus coeruleus inhibit noradrenaline output through NPY-Y1R signaling, providing bidirectional control of anxiety. Stress activates these neurons, and enhancing their activity reduces anxiety after stress.","whyItMatters":"The brain has a built-in brake system for stress responses using neuropeptide Y. Understanding this system could lead to new anxiety treatments that boost the brain's own calming mechanisms rather than suppressing the entire stress response.","specificNumbers":"Not specified quantitatively. Demonstrated bidirectional control via activation/inhibition experiments. NPY-Y1R signaling identified as mechanism.","methodology":"Functional circuit dissection in mice. Combined optogenetics, chemogenetics, in vivo fiber photometry, and NPY release measurement. Tested in naive and stress-exposed conditions.","limitations":"Mouse model only. Neural circuits may differ in humans. Manipulations are invasive and not directly translatable to therapy. Acute stress paradigm may not reflect chronic anxiety disorders."},{"rthcId":"RPEP-13267","title":"GLP-1RA based therapies in the young and old.","authors":"Rigas, Georgia; Alexander, Shirley; Haywood, Cilla J","year":2025,"journal":"Current opinion in endocrinology, diabetes, and obesity, 32(1), 26-33","doi":"10.1097/MED.0000000000000900","pmid":"39692102","tags":["glp-1-receptor-agonists","obesity-treatment","pediatric-use","aging-and-peptides","cardiovascular-outcomes"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"GLP-1 receptor agonist-based therapies show clinically significant weight loss in both young people and adults over 65. Pediatric guidelines now endorse early use, and cardiovascular outcome data support use in older adults.","whyItMatters":"Both ends of the age spectrum have unique obesity challenges. This review synthesizes evidence that GLP-1 drugs are effective across ages, though long-term safety data in the very young and very old are still maturing.","specificNumbers":"Not specified. References pediatric guideline endorsement and adult cardiovascular outcome trial data including patients over 65.","methodology":"Narrative review of GLP-1 receptor agonist data in young people (obesity and youth-onset T2D) and older adults (65+). Covers trial data, guidelines, and safety signals.","limitations":"Narrative review. No separate trials exclusively in patients over 65. Pediatric long-term safety data still limited. Heterogeneity of older adult population not fully addressed."},{"rthcId":"RPEP-13268","title":"Cardiomyopathy in the Shadow of Fibrillary Glomerulonephritis: An Unusual Indirect Association.","authors":"Rijal, Satya; Shah, Maitri P; Mudupula Vemula, Sai Sushrutha; Khanal, Prakash; Duwadi, Ayushma","year":2025,"journal":"Cureus, 17(7), e87879","doi":"10.7759/cureus.87879","pmid":"40821257","tags":["natriuretic-peptides","heart-failure","biomarkers-and-diagnostics"],"studyType":"case-report","evidenceStrength":"very-low","keyFinding":"A 60-year-old woman with fibrillary glomerulonephritis developed secondary cardiomyopathy. Treatment with prednisone and rituximab improved both kidney and heart function, with BNP levels normalizing at 12 months.","whyItMatters":"Cardiac involvement in fibrillary glomerulonephritis is very rare and poorly understood. This case suggests systemic immunologic treatment can reverse associated cardiomyopathy, with BNP serving as a useful monitoring biomarker.","specificNumbers":"Single patient. BNP normalized and LVEF improved at 6 months. ESR and CRP normalized at 12 months. Proteinuria reduced with immunosuppression.","methodology":"Single case report with clinical follow-up at 6 and 12 months. Kidney biopsy confirmed diagnosis. Echocardiographic and laboratory monitoring.","limitations":"Single case. No cardiac biopsy performed (patient refused). Cardiac improvement could be from volume management rather than direct treatment effect. Cannot establish causation."},{"rthcId":"RPEP-13269","title":"A Supramolecular Self-assembly Approach to Site-Specific Antibody Conjugates via a Coiled-coil Peptides Platform.","authors":"Ringaci, Alina; Shih, Ting-Yu; Grinstaff, Mark W","year":2025,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2025.07.21.665979","pmid":"40777265","tags":["peptide-drug-conjugates","peptide-engineering","cancer-applications","preclinical-research"],"studyType":"preclinical","evidenceStrength":"low-moderate","keyFinding":"A coiled-coil peptide platform enabled site-specific antibody conjugation under mild conditions. An ADC targeting HER2+ tumors significantly reduced tumor volume in a mouse cancer model, outperforming unconjugated antibody.","whyItMatters":"Current antibody-drug conjugate manufacturing produces uneven products. This peptide-based self-assembly method creates uniform conjugates without disrupting antibody function, potentially improving cancer drug consistency and efficacy.","specificNumbers":"Significant tumor volume reduction in HER2+ human ovarian cancer xenograft. MMAE payload. Performance validated against best-in-class therapeutic.","methodology":"Coiled-coil heterodimer peptide design for site-specific antibody conjugation. In vitro binding validation. In vivo efficacy in mouse xenograft model of HER2+ ovarian cancer.","limitations":"Preprint (bioRxiv), not peer-reviewed. Mouse xenograft model, not human trials. Single tumor type tested. Manufacturing scale-up not demonstrated. Long-term stability not assessed."},{"rthcId":"RPEP-13270","title":"Sequential enzymatic hydrolysis of egg yolk proteins: Kinetics, functionality, and bioactivity of hydrolysates.","authors":"Rios-Morales, Silvia N; Tacias-Pascacio, Veymar G; Aguilar-Uscanga, Maria Guadalupe; Torrestiana-Sánchez, Beatriz","year":2025,"journal":"International journal of biological macromolecules, 318(Pt 2), 145163","doi":"10.1016/j.ijbiomac.2025.145163","pmid":"40505913","tags":["bioactive-peptides","peptide-absorption-and-bioavailability"],"studyType":"laboratory","evidenceStrength":"low","keyFinding":"Sequential enzymatic hydrolysis of egg yolk proteins doubled antioxidant activity and tripled ACE inhibitory activity compared to unhydrolyzed protein. Peptides between 1-5 kDa were most bioactive.","whyItMatters":"Egg yolk waste from food processing contains proteins that can be converted into health-active peptides. Optimizing the enzyme treatment maximizes the yield of blood pressure-lowering and antioxidant peptides.","specificNumbers":"Sequential A-F hydrolysis: +6% degree of hydrolysis, +9% soluble protein vs single enzyme. Antioxidant activity nearly 2x, ACE inhibition nearly 3x that of unhydrolyzed LFEY. 1-5 kDa fraction most active.","methodology":"Sequential enzymatic hydrolysis with Alcalase followed by Flavourzyme under various pH and enzyme concentrations. Ultrafiltration fractionation. Antioxidant and ACE inhibitory activity assays.","limitations":"In vitro activity only. No testing in animals or humans. ACE inhibition in a test tube does not guarantee blood pressure reduction. Single protein source (egg yolk)."},{"rthcId":"RPEP-13271","title":"NRF2-mediated autophagic degradation of glycated vimentin in the skin by an elastin-derived peptide.","authors":"Ritter, Didier; Noguier, Florian; Bruno, Roman; Cavagnino, Andrea; Vaissière, Anais; Dupas, Eve; Piquemal, David; Desouches, Christophe; Courtois, Ivan; Azencot, Armand; Casoli, Vincent; Haen, Pierre; Colson, Thomas; Petit, Alain; Abraham, Jean-Daniel","year":2025,"journal":"American journal of translational research, 17(11), 8577-8588","doi":"10.62347/ZICX2570","pmid":"41415096","tags":["bioactive-peptides","collagen-and-elastin-peptides","skin-and-cosmetic-peptides"],"studyType":"preclinical","evidenceStrength":"low-moderate","keyFinding":"An elastin-derived trifunctional peptide reduced glycated vimentin in skin by activating NRF2-mediated autophagy. Clinical testing showed anti-wrinkle effects, positioning it as a candidate for anti-aging skincare.","whyItMatters":"Glycation damages skin proteins and drives visible aging. This peptide activates the skin's own cleanup machinery to remove damaged proteins, offering a mechanism-based approach to anti-aging treatment.","specificNumbers":"Reduced vimentin glycation across in vitro, ex vivo, and in vivo models. Activated NRF2 pathway genes for autophagy, proteasomal degradation, and anti-inflammation. Clinical anti-wrinkle effects confirmed.","methodology":"In vitro: human dermal fibroblasts with glyoxal-induced stress plus RNA-seq. Ex vivo: skin explants with RT-qPCR validation. In vivo: clinical cosmetic study measuring wrinkle reduction.","limitations":"Cosmetic study, not pharmaceutical-grade clinical trial. Mechanism demonstrated primarily in vitro. Clinical results may reflect short-term cosmetic effects. Specific formulation and dose not specified."},{"rthcId":"RPEP-13272","title":"Analgesia by Cryotherapy in Patients with Chronic Pain with Analysis of Pain-Modulating and Pro-Inflammatory Parameters-A Clinical Controlled Pilot Study.","authors":"Ritter, Henrike; Beuermann, Ruth; Unkelbach, Vera; Bang, Holger; Feist, Eugen","year":2025,"journal":"Journal of clinical medicine, 14(21)","doi":"10.3390/jcm14217567","pmid":"41226964","tags":["cgrp-peptides","substance-p-and-neurokinins","neuropeptides","biomarkers-and-diagnostics"],"studyType":"clinical-trial","evidenceStrength":"low-moderate","keyFinding":"Whole-body cryotherapy did not change serum levels of substance P, CGRP, or beta-NGF in chronic pain patients. Only calprotectin (an inflammatory marker) decreased, suggesting anti-inflammatory rather than neuromodulatory effects.","whyItMatters":"Cryotherapy is used for chronic pain but its mechanism is unclear. This study suggests it works through anti-inflammatory pathways rather than by altering pain-signaling neuropeptides like CGRP and substance P.","specificNumbers":"61 participants (37 WBC, 24 controls). Pain reduction >1.39 points on NRS in both groups. Calprotectin decreased (p = 0.007 overall, p = 0.032 WBC group). No changes in substance P, CGRP, beta-NGF.","methodology":"Controlled pilot study within a multimodal inpatient pain program. Serum biomarkers measured by ELISA at start and end of treatment. Pain assessed by numerical rating scale.","limitations":"Small sample. Non-randomized (controlled pilot). Multimodal treatment confounds attribution. Serum levels may not reflect tissue-level neuropeptide changes. Short observation period."},{"rthcId":"RPEP-13273","title":"The bioprospecting potential of insect venoms as antibiotics: a mini review.","authors":"Riva, Henrique G; Amarillo-S, Angela R","year":2025,"journal":"Frontiers in microbiology, 16, 1729786","doi":"10.3389/fmicb.2025.1729786","pmid":"41459233","tags":["antimicrobial-peptides","venom-derived-peptides","preclinical-research"],"studyType":"review","evidenceStrength":"low-moderate","keyFinding":"Insect venom antimicrobial peptides, particularly from wasps, bees, and ants, show broad-spectrum activity against drug-resistant bacteria with low toxicity to human cells. Key peptides include mastoparans, polydim-I, and melectin.","whyItMatters":"With antibiotic resistance rising, insect venoms offer a largely untapped source of new antimicrobial compounds. These peptides kill bacteria through membrane disruption, making resistance harder to develop.","specificNumbers":"15 original studies reviewed covering 15 years. Focus on Hymenoptera venoms. Peptides active against multidrug-resistant bacteria with low mammalian cell toxicity.","methodology":"Mini review synthesizing 15 studies from the past 15 years on antimicrobial properties of insect venom components.","limitations":"Mini review with limited scope. Most data from in vitro studies. No clinical trials. Peptide stability, delivery, and pharmacokinetics are major unresolved challenges."},{"rthcId":"RPEP-13274","title":"Effect of Tirzepatide on Body Weight and Diabetes Control in Adults With Type 1 Diabetes and Overweight or Obesity.","authors":"Rivera Gutierrez, Rene; Tama, Elif; Bechenati, Dima; Castañeda Hernandez, Regina; Bennett, Pamela K; McNally, Allyson W; Fansa, Sima; Anazco, Diego; Acosta, Andres; Hurtado Andrade, Maria D","year":2025,"journal":"Mayo Clinic proceedings, 100(2), 265-275","doi":"10.1016/j.mayocp.2024.07.006","pmid":"39601745","tags":["tirzepatide","glp-1-receptor-agonists","gip-receptor","type-1-diabetes","obesity-treatment"],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"Tirzepatide in adults with type 1 diabetes and overweight/obesity produced 8.5% weight loss, 0.9% HbA1c reduction, and 31.6% decrease in insulin requirements over a median 8 months, without increasing hypoglycemia.","whyItMatters":"Tirzepatide is not approved for type 1 diabetes, but many patients with T1D also struggle with obesity. This real-world data shows meaningful benefits with an acceptable safety profile in this off-label population.","specificNumbers":"51 patients. 58.8% female, 96.1% White, 41.2% obesity class III. Median follow-up 8 months. Weight loss: 8.5% (Q1-Q3: 5.3-13.8%). HbA1c: -0.9% (p < 0.0001). Insulin: -31.6% (p < 0.01). Nausea: 13.7%.","methodology":"Retrospective single-center study at Mayo Clinic. Adults with T1D and BMI 27+ using tirzepatide for 3+ months (June 2022 to October 2023). Data from electronic medical records.","limitations":"Retrospective, single center. Small sample (51 patients). No control group. Off-label use. Predominantly White population. Median 8-month follow-up may not capture long-term effects. Selection bias toward motivated patients."},{"rthcId":"RPEP-13275","title":"Immune versatility of oral keratinocytes: from barrier integrity to inflammation control-a mini review.","authors":"Rivera, César","year":2025,"journal":"Clinical and experimental immunology, 219(1)","doi":"10.1093/cei/uxaf069","pmid":"41092132","tags":["antimicrobial-peptides","immune-modulation"],"studyType":"review","evidenceStrength":"low-moderate","keyFinding":"Oral keratinocytes produce antimicrobial peptides like beta-defensins, regulate immune cell responses, and maintain mucosal barrier integrity. Their dysfunction drives chronic inflammatory oral diseases.","whyItMatters":"Understanding how mouth lining cells produce antimicrobial peptides and control immune responses could lead to new treatments for oral diseases like periodontitis and oral lichen planus.","specificNumbers":"Not specified. Reviews beta-defensins, pattern recognition receptors, MHC-mediated antigen presentation, and cytokine profiles.","methodology":"Narrative review synthesizing data from primary keratinocyte cultures, infection models, transcriptomics, proteomics, and immunohistochemistry.","limitations":"Narrative review. Most evidence from in vitro models. Clinical translation of keratinocyte-targeted therapies not established."},{"rthcId":"RPEP-13276","title":"Glucagon-like peptide 1 receptor agonists modestly reduced low-density lipoprotein cholesterol and total cholesterol levels independent of weight reduction: a meta-analysis and meta-regression of placebo controlled randomized controlled trials.","authors":"Rivera, Frederick Berro; Chin, Marielle Nicole Cabusas; Pine, Polyn Luz S; Ruyeras, Monica Marie Jadena; Galang, Danica Janine Cabahug; Gandionco, Keshia Marice; Morales, Benna Lynn Faye D; Climaco, Zackaree Michael V; Bantayan, Nathan Ross Baoy; Magalong, John Vincent; Mangubat, Gerard Francis; Ong, Kenneth","year":2025,"journal":"Current medical research and opinion, 41(1), 185-197","doi":"10.1080/03007995.2024.2442027","pmid":"39666879","tags":["glp-1-receptor-agonists","cardiovascular-outcomes"],"studyType":"meta-analysis","evidenceStrength":"high","keyFinding":"GLP-1 receptor agonists modestly reduced LDL cholesterol by about 3 mg/dL and total cholesterol by about 7 mg/dL compared to placebo, and these effects were independent of weight loss.","whyItMatters":"GLP-1 drugs are known for blood sugar and weight benefits. This meta-analysis shows they also have a small but real effect on cholesterol that is not just from losing weight, suggesting a direct lipid-lowering mechanism.","specificNumbers":"LDL-C: MD -2.93 mg/dL (95% CI -5.01 to -0.85, p = 0.01). TC: approximately -7 mg/dL. Triglycerides: NS (p = 0.07). VLDL-C: NS (p = 0.10). HDL-C: NS (p = 0.69). Meta-regression: weight change did not influence LDL-C or TC (R-squared = 0.0).","methodology":"Meta-analysis and meta-regression of placebo-controlled RCTs through January 2023. Random-effects model for weighted mean differences. Subgroup analyses by treatment duration.","limitations":"Modest LDL reduction (~3 mg/dL) may not be clinically meaningful alone. High heterogeneity (I-squared 99.83% for LDL). Could not determine which specific GLP-1 agents have strongest lipid effects."},{"rthcId":"RPEP-13277","title":"Sex differences in the vasoactive effect of transient receptor potential channels: TRPM3 as a new therapeutic target for (neuro)vascular disorders.","authors":"Rivera-Mancilla, Eduardo; Musterd-Bhaggoe, Usha M; Schutter, Dennis; van den Bogaerdt, Antoon; Vincent, Arnaud J P E; Villalón, Carlos M; Danser, Alexander H J; MaassenVanDenBrink, Antoinette","year":2025,"journal":"British journal of pharmacology, 182(11), 2503-2523","doi":"10.1111/bph.17472","pmid":"39956579","tags":["cgrp-peptides","migraine","cardiovascular-outcomes"],"studyType":"laboratory","evidenceStrength":"low-moderate","keyFinding":"TRPM3 channel activation caused stronger blood vessel relaxation in arteries from women than men, involving NMDA receptors and nitric oxide. TRPM3 expression was higher in female arteries.","whyItMatters":"Migraine is more common in women, and blood vessel dilation plays a role. This sex-dependent difference in TRPM3-mediated vascular relaxation could explain part of the migraine sex gap and suggests a new drug target.","specificNumbers":"TRPM3-mediated relaxation significantly greater in female vs male arteries. Expression confirmed by qPCR, western blot, and fluorescence microscopy. Blocked by isosakuranetin (TRPM3), MK-801 (NMDA), and L-NAME (NOS).","methodology":"Wire myography on human coronary and middle meningeal artery segments. Pharmacological dissection with selective antagonists. Gene expression (qPCR), protein (western blot), and localization (fluorescence microscopy).","limitations":"Ex vivo tissue study, not in vivo. Limited sample size typical of human tissue studies. Tissue from surgical patients may not represent healthy population. No migraine patient tissue specifically."},{"rthcId":"RPEP-13278","title":"Isolation of a tumor neoantigen specific CD8+ TCR from a skin biopsy of a vaccination site.","authors":"Roberti, Maria Paula; Charoentong, Pornpimol; Lyu, Yanhong; Meyer, Marten; Eichmüller, Stefan B; Schmidt, Patrick; Momburg, Frank; Cetin, Miray; Hartmann, Felix; Valous, Nektarios A; Stenzinger, Albrecht; Michel, Laura; Lichter, Peter; Schneeweiss, Andreas; Thewes, Verena; Fremd, Carlo; Zörnig, Inka; Jäger, Dirk","year":2025,"journal":"Oncoimmunology, 14(1), 2457793","doi":"10.1080/2162402X.2025.2457793","pmid":"39902862","tags":["peptide-vaccines","cancer-applications","immune-modulation"],"studyType":"case-report","evidenceStrength":"low","keyFinding":"Tumor-specific T cells were isolated from a vaccination site skin biopsy in a breast cancer patient, revealing a unique clonotype reactive to a private mutation not found in blood or tumor samples.","whyItMatters":"Finding cancer-specific immune cells has been extremely difficult. This shows vaccination sites in the skin are rich in exactly the right T cells, and a simple skin biopsy can replace complex tumor sampling for identifying therapeutic immune targets.","specificNumbers":"17 predicted MHC-binding epitopes in vaccine. Reactivity to 4 peptides detected by ELISpot. One clonotype specific to NCOR1 L1475R mutation on HLA-B*07:02. No cross-reactivity to wild-type peptide.","methodology":"Personalized neoantigen peptide vaccine in metastatic breast cancer. Skin biopsy from vaccination site after 5th cycle. VIL isolation, ELISpot, single-cell TCR sequencing, and in vitro validation.","limitations":"Single patient case. Feasibility demonstrated but clinical efficacy of identified TCR not tested. Vaccination site access depends on vaccine protocol. May not generalize to all cancer types."},{"rthcId":"RPEP-13279","title":"Association of glucagon-like peptide-1 receptor agonists with acute pancreatitis and biliary disease in individuals with diabetes and obesity: a propensity-weighted, population-based cohort study.","authors":"Robles Cabanillas, Celia; Hurtado Navarro, Isabel; García-Sempere, Aníbal; Llopis-Cardona, Fran; Sánchez-Sáez, Francisco; Rodríguez-Bernal, Clara; Sanfélix-Gimeno, Gabriel","year":2025,"journal":"Gaceta sanitaria, 39, 102444","doi":"10.1016/j.gaceta.2024.102444","pmid":"39818039","tags":["glp-1-receptor-agonists","safety-and-side-effects","type-2-diabetes"],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"GLP-1 receptor agonists showed no increased risk of acute pancreatitis (HR 0.56) or biliary disease (HR 1.12) compared to SGLT-2 inhibitors in a population-based study of diabetes and obesity patients.","whyItMatters":"Pancreatitis and gallbladder problems have been safety concerns for GLP-1 drugs. This large real-world comparison against another diabetes drug class found no increased risk, providing reassurance.","specificNumbers":"Acute pancreatitis: HR 0.56 (95% CI 0.17-1.91). Biliary disease: HR 1.12 (95% CI 0.79-1.58). Population-based study in Valencia, Spain, 2015-2021.","methodology":"Population-based, propensity-weighted, new user, active comparator cohort study. Compared GLP-1 RA initiators to SGLT-2 inhibitor initiators.","limitations":"Observational design. Wide confidence intervals for pancreatitis suggest limited events. Single Spanish region. Claims-based diagnoses may miss mild cases. Residual confounding possible."},{"rthcId":"RPEP-13280","title":"Exenatide Is Neuroprotective in a New Rabbit Model of Hypoxia-Ischemia.","authors":"Rocha-Ferreira, Eridan; Carlsson, Malin; Svedin, Pernilla; Ebefors, Kerstin; Herrock, Owen; Leverin, Anna-Lena; Hagberg, Henrik","year":2025,"journal":"Cells, 14(21)","doi":"10.3390/cells14211715","pmid":"41227362","tags":["glp-1-receptor-agonists","neurological-applications","preclinical-research"],"studyType":"preclinical","evidenceStrength":"low-moderate","keyFinding":"Exenatide (a GLP-1 receptor agonist) reduced brain tissue loss by 90% in newborn rabbits after hypoxic-ischemic brain injury. The effect was accompanied by a transient increase in ketone bodies but no changes in glucose or temperature.","whyItMatters":"Brain injury from oxygen deprivation at birth is a major cause of disability in newborns. This rabbit model, which is closer to human brain development than mouse models, shows exenatide may provide powerful neuroprotection.","specificNumbers":"500 micrograms/g exenatide reduced brain tissue loss by 90% (both 1-dose and 2-dose). 170 micrograms/g was less effective. Ketone bodies doubled transiently (0.6 to 1.3 mmol/L at 6 hours). No effect on glucose, temperature, or weight.","methodology":"New reproducible hypoxia-ischemia model in rabbit kits at postnatal day 3-4. Multiple exenatide dose regimens tested. Brain histology at 7 days. Metabolic parameters (glucose, ketones, temperature, weight) measured at early timepoints.","limitations":"Animal model only. Rabbit brain, while more mature than rodent, still differs from human. Small group sizes. Seven-day endpoint may not capture long-term outcomes. No functional neurological assessment."},{"rthcId":"RPEP-13281","title":"Calcitonin gene-related peptide monoclonal antibodies and medication-overuse headache: stopping excessive pain medication is still necessary.","authors":"Rocha-Filho, Pedro Augusto Sampaio","year":2025,"journal":"Arquivos de neuro-psiquiatria, 83(9), 1-4","doi":"10.1055/s-0045-1809332","pmid":"40720967","tags":["cgrp-peptides","cgrp-monoclonal-antibodies","migraine"],"studyType":"review","evidenceStrength":"low-moderate","keyFinding":"Despite CGRP monoclonal antibodies being effective for chronic migraine, stopping excessive use of symptomatic pain medications remains necessary for treating medication-overuse headache.","whyItMatters":"Some clinicians hope CGRP drugs alone can fix medication-overuse headache. This review argues that behavioral change in stopping painkiller overuse is still essential for recovery.","specificNumbers":"Medication-overuse headache affects 1-2% of the global population.","methodology":"Narrative review presented as part of a controversy session. Reviews and critically analyzes literature on medication-overuse headache management.","limitations":"Narrative review representing one side of a controversy. Limited evidence from randomized trials comparing CGRP mAbs with vs. without medication withdrawal."},{"rthcId":"RPEP-13282","title":"Obesity treatment as a bridge to solid organ transplantation: A comparison of bariatric surgery to medical therapy.","authors":"Roddy, Kevin L; Greenwald, Matthew R; Hollman, Nicholas; Dorand, Madisen F; Richards, Jesse R","year":2025,"journal":"Obesity pillars, 16, 100199","doi":"10.1016/j.obpill.2025.100199","pmid":"40918087","tags":["tirzepatide","semaglutide","glp-1-receptor-agonists","gip-receptor","obesity-treatment"],"studyType":"case-series","evidenceStrength":"very-low","keyFinding":"Tirzepatide helped 78% of kidney transplant candidates with severe obesity meet the BMI cutoff for surgery, producing weight loss close to bariatric surgery without the surgical risks.","whyItMatters":"Many patients cannot get organ transplants because of obesity. GLP-1 drugs offer a non-surgical path to qualifying, which is critical for patients too sick for bariatric surgery.","specificNumbers":"19 patients. Tirzepatide (n=9): 77.8% met BMI cutoff, 8% less weight loss than surgery. Semaglutide (n=4): 50% met cutoff. Bariatric surgery (n=3): 66.7%. Combined (n=3): 100%.","methodology":"Retrospective descriptive case series comparing bariatric surgery alone, GLP-1/GIP medication alone, and combined approaches in kidney transplant candidates.","limitations":"Very small sample (19 patients). Retrospective. No randomization. Groups not comparable in size or baseline characteristics. Single center. Short follow-up."},{"rthcId":"RPEP-13283","title":"Liraglutide-Driven Weight Loss Modulates Placental Remodeling in Obese Pregnancies in Mice.","authors":"Rodrigo, Natassia; Aksentijevic, Dunja; Patel, Nikayla; Pollock, Carol A; McClements, Lana; Glastras, Sarah J","year":2025,"journal":"Cells, 14(24)","doi":"10.3390/cells14242009","pmid":"41440029","tags":["liraglutide","glp-1-receptor-agonists","preclinical-research"],"studyType":"animal-study","evidenceStrength":"low","keyFinding":"Pre-conception liraglutide treatment in obese mice reduced placental metabolic stress markers but not inflammation. Diet change alone addressed both oxidative stress and inflammation in the placenta.","whyItMatters":"Maternal obesity harms placental function. This study shows that while liraglutide helps with metabolic stress before pregnancy, diet change provides broader placental benefits, suggesting the two approaches have different mechanisms.","specificNumbers":"Liraglutide 0.3 mg/kg/day subcutaneously for 4 weeks pre-pregnancy. HFD placentas showed lower aspartate, glutamate, and glutamine (p < 0.05). Analysis at day 18-20 of gestation.","methodology":"Mouse model of maternal obesity (C57BL/6 on high-fat diet). Pre-pregnancy interventions: diet switch to chow, liraglutide on HFD, or post-conception diet switch. Placental metabolomics (1H NMR) and gene expression analysis.","limitations":"Mouse model. Liraglutide given pre-conception only, not during pregnancy. Short treatment period. Single dose tested. Mouse placental biology differs from human."},{"rthcId":"RPEP-13284","title":"Host defense peptides as a new drug lead to a strategy for inflammatory bowel disease.","authors":"Rodrigues, Júlia Morales; Ferreira Leal, Ana Paula; Buccini, Danieli Fernanda; Franco, Octavio Luiz","year":2025,"journal":"Drug discovery today, 30(12), 104535","doi":"10.1016/j.drudis.2025.104535","pmid":"41241376","tags":["antimicrobial-peptides","immune-modulation","gut-peptides"],"studyType":"review","evidenceStrength":"low-moderate","keyFinding":"Host defense peptides including cathelicidins, defensins, cecropins, and others show therapeutic potential for inflammatory bowel disease through both antimicrobial and immunomodulatory mechanisms, particularly NF-kB pathway regulation.","whyItMatters":"Current IBD treatments have significant side effects. Host defense peptides could offer a dual-action alternative that fights infection and calms inflammation simultaneously.","specificNumbers":"Not specified. Reviews multiple peptide families: cathelicidins (LL-37 variants), defensins (HD-5, hBD2), cecropins (CC34), microcins (MccJ25), brevinins, PrAMPs, and alpha-MSH (KPV).","methodology":"Short narrative review of host defense peptide biology and their potential application in inflammatory bowel disease.","limitations":"Brief review. Most evidence preclinical. No clinical trial data for most peptides discussed. Drug delivery and stability challenges not addressed in depth."},{"rthcId":"RPEP-13285","title":"3D tubular constructs based on natural polysaccharides and recombinant polypeptide synergistic blends as potential candidates for blood vessel solutions.","authors":"Rodrigues, L C; Gomes, J M; da Costa, D Soares; Fernandes, E M; Costa, R R; Rodriguez-Cabello, J C; Silva, S S; Reis, R L","year":2025,"journal":"International journal of biological macromolecules, 310(Pt 3), 143084","doi":"10.1016/j.ijbiomac.2025.143084","pmid":"40250666","tags":["bioactive-peptides","peptide-engineering","drug-delivery-systems"],"studyType":"laboratory","evidenceStrength":"low","keyFinding":"Tubular tissue engineering constructs incorporating a VEGF-mimicking peptide (QK) via elastin-like recombinamers supported endothelial cell survival and showed sustained bioactive release, relevant to blood vessel engineering.","whyItMatters":"Growing blood vessels in the lab is essential for tissue engineering. This study combines natural materials with a peptide that mimics a key blood vessel growth factor, creating tubes that could serve as artificial blood vessels.","specificNumbers":"Water absorption about 20x dry mass. Structural integrity maintained 7 days. Pore size maintained over 100 microns after ELR modification. Sustained release of ACE and ELRs improved endothelial cell viability.","methodology":"Freeze-drying fabrication of polysaccharide tubes. Incorporation of elastin-like recombinamers with QK peptide. Characterized by SEM, Micro-CT, water uptake, stability, and cell viability assays.","limitations":"In vitro study only. No in vivo implantation or blood flow testing. Single peptide sequence tested. Long-term durability and immune response unknown."},{"rthcId":"RPEP-13286","title":"Antiobesity medications in adult and pediatric obesity and metabolic dysfunction-associated steatotic liver disease.","authors":"Rodriguez, Natalie; Hartmann, Phillipp","year":2025,"journal":"Pharmacological reviews, 77(4), 100058","doi":"10.1016/j.pharmr.2025.100058","pmid":"40554267","tags":["semaglutide","tirzepatide","glp-1-receptor-agonists","obesity-treatment","liver-disease","drug-development-pipeline"],"studyType":"review","evidenceStrength":"high","keyFinding":"Semaglutide, tirzepatide, and retatrutide achieve placebo-subtracted weight loss of 10.8%, 17.8%, and 22.1% respectively in adults. For liver disease, tirzepatide resolves MASH in 53% and retatrutide reduces liver fat by 81%.","whyItMatters":"These drugs are transforming both obesity and liver disease treatment. Retatrutide's 22% weight loss and 81% liver fat reduction represent unprecedented results that could change the treatment landscape for both conditions.","specificNumbers":"Placebo-subtracted weight loss: semaglutide 10.8%, tirzepatide 17.8%, retatrutide 22.1% (48-72 weeks). MASH resolution: semaglutide 41%, tirzepatide 53%. Liver fat reduction: semaglutide 41%, tirzepatide 47%, retatrutide 81%. Adolescent BMI reduction: semaglutide 16.7% (68 weeks).","methodology":"Comprehensive review of development, mechanisms, and published efficacy data from double-blind RCTs for approved and off-label antiobesity drugs in adult and pediatric obesity and MASLD.","limitations":"Review article. Most liver biopsy data from adult trials only. No pediatric biopsy-based MASLD trials. Retatrutide data from early-phase trials. Long-term fibrosis outcomes still limited."},{"rthcId":"RPEP-13287","title":"De-intensification of basal-bolus therapy by replacing prandial insulin with once-weekly subcutaneous semaglutide in individuals with well-controlled type 2 diabetes: A single-centre, open-label randomised trial (TRANSITION-T2D).","authors":"Rodriguez, Paloma; Breslaw, Nikki; Xiao, Huijun; Bena, Jim; Jenkins, Kimberly; Isaacs, Diana; Zhou, Keren; Griebeler, Marcio L; Burguera, Bartolome; Pantalone, Kevin M","year":2025,"journal":"Diabetes, obesity & metabolism, 27(2), 642-651","doi":"10.1111/dom.16057","pmid":"39532398","tags":["semaglutide","glp-1-receptor-agonists","type-2-diabetes","insulin-therapy"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"Replacing prandial insulin with weekly semaglutide in well-controlled T2D patients maintained HbA1c in 90% while producing 8.9 kg weight loss. Nearly all patients stopped mealtime insulin injections.","whyItMatters":"Many people with type 2 diabetes take multiple daily insulin injections. Switching mealtime insulin to weekly semaglutide maintained blood sugar control while dramatically reducing injection burden and causing significant weight loss.","specificNumbers":"60 patients. 90% vs 75% maintained HbA1c 7.5% or under (p = 0.18). HbA1c change: -0.5% vs 0.0% (p = 0.009). Weight: -8.9 kg vs +1.5 kg (p < 0.001). 97.5% stopped prandial insulin. 45% lost over 10% body weight. Insulin TDD reduced over 50%.","methodology":"Single-center, randomized, open-label trial (TRANSITION-T2D). 60 adults with HbA1c 7.5% or under on MDI with TDD 120 units/day or under. 2:1 randomization to semaglutide 1.0 mg plus degludec vs. continued MDI. 26-week follow-up.","limitations":"Open-label design. Small sample (60 patients). Single center. Only well-controlled patients included (HbA1c 7.5% or under). 26-week duration. Semaglutide dose was 1.0 mg (not the higher 2.4 mg weight management dose)."},{"rthcId":"RPEP-13288","title":"Discontinuation and Reinitiation of Dual-Labeled GLP-1 Receptor Agonists Among US Adults With Overweight or Obesity.","authors":"Rodriguez, Patricia J; Zhang, Vincent; Gratzl, Samuel; Do, Duy; Goodwin Cartwright, Brianna; Baker, Charlotte; Gluckman, Ty J; Stucky, Nicholas; Emanuel, Ezekiel J","year":2025,"journal":"JAMA network open, 8(1), e2457349","doi":"10.1001/jamanetworkopen.2024.57349","pmid":"39888616","tags":["glp-1-receptor-agonists","semaglutide","liraglutide","tirzepatide","obesity-treatment","real-world-evidence"],"studyType":"observational","evidenceStrength":"high","keyFinding":"Among 125,474 US adults, 65% without diabetes discontinued GLP-1 RAs within one year vs. 47% with diabetes. Weight loss predicted staying on treatment; GI side effects and lower income predicted stopping.","whyItMatters":"This is the largest study of GLP-1 RA adherence patterns. It reveals that most patients stop these drugs within a year, especially those using them for weight loss without diabetes, highlighting a major treatment gap.","specificNumbers":"125,474 adults (65.4% women, mean age 54.4). 1-year discontinuation: 64.8% without T2D, 46.5% with T2D. Each 1% weight loss reduced discontinuation hazard by 3.1-3.3%. GI adverse events: HR 1.19-1.38 for discontinuation. Income >$80K: HR 0.72 for discontinuation (T2D only). 1-year reinitiation: 36.3% without T2D, 47.3% with T2D.","methodology":"Retrospective cohort using electronic health records from multiple US health systems. 2018-2023. Kaplan-Meier for discontinuation/reinitiation. Time-varying Cox regression for predictors. Up to 4-year follow-up.","limitations":"EHR-based, may miss prescriptions filled outside system. Cannot distinguish intentional discontinuation from access barriers. Observational design. US-specific. Newer agents (tirzepatide) had shorter follow-up."},{"rthcId":"RPEP-13289","title":"Alopecia as an Emerging Adverse Effect Associated With Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists for Weight Loss: A Scoping Review.","authors":"Rojas Lopez, Ricardo Flaminio; Lynett Barrera, Daniela; Amaya Muñoz, Maria Camila; Saavedra Diaz, Maria Paula","year":2025,"journal":"Cureus, 17(8), e90021","doi":"10.7759/cureus.90021","pmid":"40951222","tags":["glp-1-receptor-agonists","semaglutide","liraglutide","tirzepatide","safety-and-side-effects"],"studyType":"systematic-review","evidenceStrength":"low-moderate","keyFinding":"Hair loss has emerged as a potential side effect of GLP-1 receptor agonists, with over 1,000 cases reported to the FDA. Telogen effluvium and androgenetic alopecia are the most common patterns identified.","whyItMatters":"Hair loss can significantly affect quality of life and medication adherence. As GLP-1 drug use explodes, recognizing this emerging side effect early helps clinicians counsel patients and avoid unnecessary diagnostic workups.","specificNumbers":"9 studies met inclusion criteria. Over 1,000 spontaneous cases in FAERS. Telogen effluvium and androgenetic alopecia most common patterns. Reports span semaglutide, liraglutide, tirzepatide, and dulaglutide.","methodology":"Scoping review following systematic search of PubMed, Scopus, Google Scholar, Cochrane, and LILACS through May 2025. Included RCTs, cohort studies, and pharmacovigilance analyses.","limitations":"Cannot confirm causation. Rapid weight loss itself causes telogen effluvium. Most studies lacked dermatological confirmation. FAERS reports are spontaneous and subject to reporting bias."},{"rthcId":"RPEP-13290","title":"Patients With Severe Obesity Are Made Eligible for Complex Abdominal Wall Repair After Preoptimization With GLP-1 Agonists: Results of a Bicentric Pilot Study.","authors":"Romain, Benoit; Pfirsch, Vincent; Manfredelli, Simone; Leroi, Thomas; Salman, Fadi; Sami, Ouidad; Westerfeld-Ruillier, Diane; Ledoux, Séverine; Moszkowicz, David","year":2025,"journal":"World journal of surgery, 49(4), 898-905","doi":"10.1002/wjs.12547","pmid":"40088135","tags":["semaglutide","glp-1-receptor-agonists","obesity-treatment"],"studyType":"observational","evidenceStrength":"low-moderate","keyFinding":"GLP-1 agonists enabled 63% of severely obese patients to reach BMI under 35 for hernia repair surgery, with 11.3% average weight loss. Semaglutide 2.4 mg produced the greatest weight reduction.","whyItMatters":"Patients with severe obesity cannot safely undergo complex hernia repair. GLP-1 drugs offer a new preoperative optimization tool, allowing two-thirds of patients to become surgical candidates without needing bariatric surgery first.","specificNumbers":"24 GLP-1 patients vs 52 controls. Mean starting BMI 40.1. Average weight loss 11.3%. Success rate (BMI under 35): 62.5%. Semaglutide (n=12, 50%), dulaglutide (n=7), liraglutide (n=5). Complications: 45.8% vs 59.6% (p = 0.2).","methodology":"Bicentric pilot study comparing GLP-1 agonist-treated hernia patients to a historical cohort with conventional nutritional management. Retrospective analysis of weight loss and surgical outcomes.","limitations":"Small sample. Non-randomized with historical controls. Pilot study. Complication difference not statistically significant. Mixed GLP-1 agents. Selection bias possible."},{"rthcId":"RPEP-13291","title":"Use of semaglutide in a 54-year-old patient with cocaine abuse and weight loss: a case report.","authors":"Romeo, V M","year":2025,"journal":"Journal of medical case reports, 19(1), 57","doi":"10.1186/s13256-025-05049-w","pmid":"39962582","tags":["semaglutide","glp-1-receptor-agonists","substance-use-and-addiction"],"studyType":"case-report","evidenceStrength":"very-low","keyFinding":"A 54-year-old man with both obesity and cocaine use disorder showed significant weight loss and markedly reduced cocaine craving after 12 weeks of semaglutide treatment.","whyItMatters":"GLP-1 drugs act on brain reward centers that drive both food and drug cravings. This case adds to growing evidence that semaglutide might help treat substance use disorders alongside obesity.","specificNumbers":"Single patient, 54 years old. 12 weeks of progressive semaglutide dosing. Significant weight loss and reduced cocaine craving reported.","methodology":"Single case report with clinical and psychodiagnostic monitoring over 12 weeks of subcutaneous semaglutide treatment.","limitations":"Single case. No control or comparator. Placebo effect and expectation bias cannot be excluded. Psychodiagnostic tools for craving measurement not standardized across studies. Short follow-up."},{"rthcId":"RPEP-13292","title":"Management of local and delayed cutaneous hypersensitivity reactions to anti-CGRP antibodies: implications for continuing treatment.","authors":"Romero Del Rincon, Celia; Panos Basterra, Paula; Heredia-Rodriguez, Patricia; Serra López-Matencio, José María; Vega, Francisco; Gago-Veiga, Ana Beatriz","year":2025,"journal":"Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 46(10), 5431-5435","doi":"10.1007/s10072-025-08269-6","pmid":"40456979","tags":["cgrp-peptides","cgrp-monoclonal-antibodies","migraine","safety-and-side-effects"],"studyType":"case-series","evidenceStrength":"very-low","keyFinding":"A four-step tolerance protocol (antihistamine, abdominal injection site, NSAID with cold compress, topical treatment) allowed three patients with delayed skin reactions to continue anti-CGRP antibody treatment.","whyItMatters":"Skin reactions cause some patients to stop effective migraine prevention. A simple protocol that manages these reactions keeps patients on therapy without requiring drug switching.","specificNumbers":"3 patients. Protocol applied to reactions from erenumab, galcanezumab, and fremanezumab. Symptoms markedly reduced or fully resolved in all cases.","methodology":"Case series of three patients with delayed skin reactions to anti-CGRP mAbs. Structured tolerance protocol developed and applied. Clinical outcome assessed.","limitations":"Only three patients. No control group. Cannot rule out natural resolution. Protocol not tested in a formal trial. May not work for severe allergic reactions."},{"rthcId":"RPEP-13293","title":"B-type natriuretic peptide changes and left ventricular remodeling dynamics in heart failure with reduced ejection fraction.","authors":"Romero, Erick; Kushnir, Yevhen; Shahzad, Areej; Patel, Dev Jaydeep; Heejung, Bang; Sirish, Padmini; Chiamvimonvat, Nipavan; Liem, David A; Cadeiras, Martin","year":2025,"journal":"Frontiers in cardiovascular medicine, 12, 1666067","doi":"10.3389/fcvm.2025.1666067","pmid":"41584282","tags":["natriuretic-peptides","heart-failure","biomarkers-and-diagnostics"],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"Decreasing BNP levels over time correlated with improved left ventricular dimensions and ejection fraction in heart failure patients, while rising BNP predicted worse remodeling and higher mortality.","whyItMatters":"BNP is already used to diagnose heart failure, but this study shows tracking BNP changes over time can predict whether the heart is recovering or deteriorating, making it a dynamic monitoring tool.","specificNumbers":"887 patients. BNP change tertiles: decreasing (-63.3 to -10.4%), minimal (-10.4 to 2.8%), rising (2.9 to 12.6%). Decreasing tertile showed improved LVIDs (p = 0.001), LVIDd (p = 0.006), and LVEF (p = 0.008). Rising tertile had higher mortality (p < 0.05).","methodology":"Single-center retrospective cohort. Inclusion: LVEF under 40%, BNP 100+ pg/mL at baseline, follow-up BNP within one year. BNP change divided into tertiles. Endpoints: LV dimensions, LVEF, all-cause mortality.","limitations":"Retrospective single center. BNP influenced by many factors beyond cardiac remodeling (renal function, medications, volume status). Tertile cutoffs are data-derived. Selection bias from requiring follow-up BNP."},{"rthcId":"RPEP-13294","title":"B-type Natriuretic Peptide Changes and Left Ventricular Remodeling Dynamics in Heart Failure with Reduced Ejection Fraction.","authors":"Romero, Erick; Kushnir, Yevhen; Mendoza-Quispe, Daniel; Shahzad, Areej; Patel, Dev Jaydeep; Omadevuae, Kafayat; Sirish, Padmini; Chiamvimonvat, Nipavan; Liem, David A; Cadeiras, Martin","year":2025,"journal":"medRxiv : the preprint server for health sciences","doi":"10.1101/2025.10.02.25337215","pmid":"41256178","tags":["natriuretic-peptides","heart-failure","biomarkers-and-diagnostics"],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"This is a preprint version of the same BNP and left ventricular remodeling study published as RPEP-12513. Decreasing BNP levels correlated with improved heart structure and survival in HFrEF patients.","whyItMatters":"Preprint of peer-reviewed publication. See RPEP-12513 for the published version with identical findings.","specificNumbers":"887 patients. Same results as RPEP-12513.","methodology":"Single-center retrospective cohort. Preprint version of published study.","limitations":"Preprint, not yet peer-reviewed at time of indexing. Same limitations as RPEP-12513."},{"rthcId":"RPEP-13295","title":"Optimising combined treatment for migraine and temporomandibular disorders (TMDs).","authors":"Romero-Reyes, Marcela; Akerman, Simon; Rapoport, Alan M","year":2025,"journal":"Cephalalgia : an international journal of headache, 45(9), 3331024251368882","doi":"10.1177/03331024251368882","pmid":"40936448","tags":["cgrp-peptides","cgrp-monoclonal-antibodies","migraine"],"studyType":"review","evidenceStrength":"low-moderate","keyFinding":"Migraine and temporomandibular disorders share trigeminal system pathways and mutually worsen each other. CGRP-targeting therapies may offer future dual treatment, but no integrated protocols currently exist.","whyItMatters":"Many migraine patients also have jaw pain from TMD, and each condition makes the other worse. CGRP is involved in both, so drugs targeting it could potentially treat both at once.","specificNumbers":"Not specified. Reviews evidence for CGRP involvement in both migraine and TMD pathophysiology.","methodology":"Narrative review covering pathophysiology, shared mechanisms, and management strategies for comorbid migraine and TMD. Proposes an integrated treatment framework.","limitations":"No clinical trials testing CGRP drugs specifically for TMD. Proposed multidisciplinary framework not validated. Limited evidence for specific combination protocols."},{"rthcId":"RPEP-13296","title":"Sucralose consumption modifies glucose homeostasis, gut microbiota, Curli protein, and related metabolites in healthy individuals: A randomized placebo-controlled, triple-blind trial.","authors":"Romo-Romo, Alonso; Sánchez-Tapia, Mónica; López-Carrasco, M Guadalupe; Guillén-Pineda, Luz E; Brito-Córdova, Griselda X; Martagón, Alexandro J; Granados-Portillo, Omar; Walther, Guillaume; Gómez-Pérez, Francisco J; Aguilar-Salinas, Carlos A; Tovar, Armando R; Torres, Nimbe; Almeda-Valdes, Paloma","year":2025,"journal":"Clinical nutrition ESPEN, 69, 733-744","doi":"10.1016/j.clnesp.2025.08.029","pmid":"40907790","tags":["glp-1-receptor-agonists","gut-peptides","type-2-diabetes"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"Consuming sucralose at 30% of the acceptable daily intake for 30 days reduced insulin sensitivity by 20.3% in healthy lean people, while also reducing gut microbiome diversity and increasing inflammatory markers.","whyItMatters":"Artificial sweeteners are assumed safe, but this trial shows sucralose measurably impairs insulin sensitivity in healthy people within a month. The mechanism may involve gut microbiome changes and increased GLP-1 secretion.","specificNumbers":"20.3% decrease in insulin sensitivity (Matsuda index). Increased GLP-1, glucose, and insulin AUC after mixed meal. Reduced alpha-diversity. Increased BCAA, acetate, fecal Curli protein. Decreased fecal butyrate. 30 days at 30% ADI.","methodology":"Randomized, placebo-controlled, triple-blind trial in healthy lean adults. 30 days of sucralose at 30% ADI or placebo. Mixed meal tolerance tests pre- and post-intervention. 16S rRNA gut microbiota sequencing. NCT06094894.","limitations":"Short duration (30 days). Healthy lean participants only. Single dose level tested. Small sample (size not stated in abstract). GLP-1 increase mechanism unclear. Reversibility of effects not studied."},{"rthcId":"RPEP-13297","title":"A nomogram for the prediction of response to anti-CGRP mAbs: the CGRP score.","authors":"Romozzi, Marina; Lokhandwala, Ammar; Vollono, Catello; García-Azorín, David; Vigani, Giulia; De Cesaris, Francesco; Altamura, Claudia; Vernieri, Fabrizio; Calabresi, Paolo; Di Tella, Sonia; Iannone, Luigi Francesco","year":2025,"journal":"The journal of headache and pain, 26(1), 190","doi":"10.1186/s10194-025-02138-5","pmid":"40890582","tags":["cgrp-peptides","cgrp-monoclonal-antibodies","migraine","biomarkers-and-diagnostics"],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"A machine learning model achieved 74% accuracy in predicting who will respond to anti-CGRP monoclonal antibodies. The resulting nomogram (CGRP Score) uses baseline features to estimate response probability.","whyItMatters":"CGRP antibodies do not work for all migraine patients. A predictive tool that identifies likely responders before starting treatment could save time, money, and avoid unnecessary drug exposure.","specificNumbers":"429 patients (310 completed 12 months). 55% classified as responders (50%+ MHD reduction). Model F1-score: 70.5%. External validation accuracy: 74%. Precision for responders: 0.75, recall: 0.84.","methodology":"Prospective cohort from two headache centers. Logistic regression ML model trained on 80%, tested on 20% plus external validation cohort (109 patients). 11 baseline variables. Nomogram created.","limitations":"Moderate accuracy (74%). Needs further external validation. ML model based on logistic regression, not deep learning. 11 variables may not capture all predictors. Specialist headache center population may not generalize."},{"rthcId":"RPEP-13298","title":"Cerebrospinal fluid and serum biomarkers in idiopathic intracranial hypertension: A systematic review.","authors":"Romozzi, Marina; Zeoli, Fabio; Martinelli, Renata; Tosto, Federico; Funcis, Antonio; Garignano, Giuseppe; Chiloiro, Sabrina; Di Nardo, Lucia; Vollono, Catello; Olivi, Alessandro; Calabresi, Paolo; Signorelli, Francesco","year":2025,"journal":"Headache, 65(8), 1462-1476","doi":"10.1111/head.15023","pmid":"40781762","tags":["cgrp-peptides","biomarkers-and-diagnostics","neurological-applications"],"studyType":"systematic-review","evidenceStrength":"low-moderate","keyFinding":"Plasma CGRP levels were elevated in idiopathic intracranial hypertension patients, especially those with migraine-like headache. Leptin, cortisol dysregulation, and neurofilament light chain were also consistently altered.","whyItMatters":"CGRP may emerge as both a biomarker and treatment target for headache in IIH, a condition where headache is the main symptom but treatment options are limited.","specificNumbers":"38 studies reviewed. Two studies found elevated plasma CGRP in IIH. NfL elevated and correlated with disease severity. Leptin consistently elevated.","methodology":"Systematic review per PRISMA guidelines. Registered in PROSPERO. Searched PubMed, Web of Science, and Scopus (1995-2024). ROBINS-I for risk of bias.","limitations":"Substantial heterogeneity across studies. Only two CGRP studies in IIH. Most biomarker findings lack replication. Small study sizes throughout. No meta-analysis possible due to heterogeneity."},{"rthcId":"RPEP-13299","title":"Pharmacological differences and switching among anti-CGRP monoclonal antibodies: A narrative review.","authors":"Romozzi, Marina; Munafò, Antonio; Burgalassi, Andrea; De Cesaris, Francesco; Vigani, Giulia; Altamura, Claudia; Rivi, Veronica; Guerzoni, Simona; Calabresi, Paolo; Raffaelli, Bianca; Iannone, Luigi Francesco","year":2025,"journal":"Headache, 65(2), 342-352","doi":"10.1111/head.14903","pmid":"39825578","tags":["cgrp-peptides","cgrp-monoclonal-antibodies","migraine"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Despite similar overall efficacy as a class, anti-CGRP monoclonal antibodies differ in target (ligand vs. receptor), structure, and pharmacokinetics, providing rationale for switching between agents when one fails.","whyItMatters":"When patients do not respond to one CGRP antibody, switching to another may work because of pharmacological differences. This review provides the scientific basis for switching decisions.","specificNumbers":"Not specified. Reviews pharmacokinetic differences among erenumab, galcanezumab, fremanezumab, and eptinezumab.","methodology":"Narrative review of pharmacological characteristics, mechanisms of action, pharmacokinetic profiles, and clinical switching data for anti-CGRP monoclonal antibodies.","limitations":"Narrative review. Limited controlled switching studies. Most switching evidence from observational data. Optimal switching algorithms not established."},{"rthcId":"RPEP-13300","title":"Dual-targeting fluorous peptide proteolysis-targeting chimeras for cancer therapy.","authors":"Rong, Guangyu; Li, Yuhan; Zhu, Fang; Lu, Yiteng; Sun, Zhengwang; Hong, Jiaxu; Cheng, Yiyun","year":2025,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 391, 114591","doi":"10.1016/j.jconrel.2025.114591","pmid":"41478376","tags":["peptide-drug-conjugates","cancer-applications","peptide-engineering","preclinical-research"],"studyType":"preclinical","evidenceStrength":"low-moderate","keyFinding":"A dual-targeting peptide-based PROTAC simultaneously degraded PD-L1 and Bcl-xL in melanoma, restoring both antitumor immunity and cancer cell death sensitivity with excellent biocompatibility in mice.","whyItMatters":"Cancer often evades treatment by blocking immune attack and resisting cell death simultaneously. This peptide platform degrades two key cancer proteins at once, offering a new approach to combination cancer therapy.","specificNumbers":"Simultaneous degradation of extracellular PD-L1 and cytosolic Bcl-xL. Superior antitumor efficacy in B16-F10 melanoma mice. Excellent biocompatibility.","methodology":"Designed fluorous peptide PROTACs targeting PD-L1 and Bcl-xL. Self-assembly into nanoparticles characterized. Cellular uptake via macropinocytosis. Degradation via ubiquitin-proteasome system. In vivo testing in melanoma mouse model.","limitations":"Mouse model only. Single tumor type tested. Long-term safety not assessed. Manufacturing scalability unknown. No comparison to existing checkpoint inhibitor or Bcl-xL inhibitor therapies."},{"rthcId":"RPEP-13301","title":"Substance P and neurokinin 1 receptor boost the pathogenicity of granulocyte-macrophage colony-stimulating factor-producing T helper cells in dry eye disease.","authors":"Rong, Hua; Yang, Hai; Liu, Qingqing; Zhang, Hui; Wang, Shaolin","year":2025,"journal":"Scandinavian journal of immunology, 101(1), e13434","doi":"10.1111/sji.13434","pmid":"39789752","tags":["substance-p-and-neurokinins","neuropeptides","immune-modulation","preclinical-research"],"studyType":"preclinical","evidenceStrength":"low","keyFinding":"Substance P amplified the pathogenicity of GM-CSF-producing T helper cells in dry eye disease through the NK1R receptor. Blocking NK1R reduced disease severity in a mouse model.","whyItMatters":"Dry eye disease is an inflammatory condition where neuropeptides and immune cells interact. Identifying the substance P-NK1R axis as a driver opens a new therapeutic target for this common condition.","specificNumbers":"Substance P increased GM-CSF expression in ThGM cells. NK1R-expressing ThGM transfer significantly exacerbated DED. NK1R-knockdown ThGM weakly aggravated DED. NK2R knockdown had no effect.","methodology":"Murine dry eye disease model. Characterized NK1R and NK2R expression on ThGM and Th1 cells. Substance P and NKA stimulation assays. Adoptive transfer of NK1R-expressing vs. NK1R-knockdown ThGM cells.","limitations":"Mouse model only. DED in humans may involve different immune mechanisms. Adoptive transfer experiments are artificial. NK1R antagonists not tested therapeutically."},{"rthcId":"RPEP-13302","title":"Microglial activation and hypothalamic structural plasticity in HFD obesity: insights from semaglutide and minocycline.","authors":"Rong, Xi; Wei, Fang; Jiang, Yuqi; Ma, Qintao; Wang, Dongmei; Shen, Jie","year":2025,"journal":"Journal of lipid research, 66(2), 100736","doi":"10.1016/j.jlr.2024.100736","pmid":"39724960","tags":["semaglutide","glp-1-receptor-agonists","neurological-applications","preclinical-research","obesity-treatment"],"studyType":"preclinical","evidenceStrength":"low-moderate","keyFinding":"Semaglutide and minocycline both reversed high-fat-diet-induced microglial activation in the hypothalamus and restored synaptic structures, but through different therapeutic pathways.","whyItMatters":"Obesity damages the brain's appetite-control center through immune cell activation that eats away at nerve connections. Understanding that semaglutide reverses this damage helps explain its effects beyond simple appetite suppression.","specificNumbers":"30 weeks HFD followed by 6 weeks treatment. Semaglutide and minocycline both reversed increased CD68/synaptophysin/CD11b colocalization with Iba-1, and elevated C1q/C3/CD11b expression. Both restored dendritic spines and synaptic markers.","methodology":"C57BL/6J mice on HFD for 30 weeks then treated with daily semaglutide or minocycline for 6 weeks. Confocal microscopy for dendritic spines, synaptic organization, and microglia-synapse interactions. BV2 microglial cell line for in vitro validation.","limitations":"Mouse model. Daily semaglutide dosing differs from human weekly dosing. Minocycline has many effects beyond microglial inhibition. Six-week treatment period. Cannot separate direct CNS effects from peripheral metabolic improvements."},{"rthcId":"RPEP-13303","title":"CGRP-targeted therapy fulfilling the treatment gap in medication-underuse setting: a retrospective cohort study at a tertiary headache center in Thailand, a lower-middle-income country.","authors":"Roongrojwittayakul, Sirawit; Anukoolwittaya, Prakit; Hiransuthikul, Akarin; Pongpitakmetha, Thanakit; Thanprasertsuk, Sekh; Rattanawong, Wanakorn","year":2025,"journal":"The journal of headache and pain, 26(1), 224","doi":"10.1186/s10194-025-02160-7","pmid":"41107729","tags":["cgrp-peptides","cgrp-monoclonal-antibodies","migraine"],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"No patients discontinued CGRP monoclonal antibodies over 6 months at a Thai headache center, while 25-54% discontinued other preventive medications. CGRP mAb use was associated with discontinuing other oral preventives, suggesting de-escalation.","whyItMatters":"In countries with limited medication access, CGRP antibodies may actually reduce polypharmacy by replacing less-tolerated oral medications, addressing 'medication underuse headache' where patients stop preventives too soon.","specificNumbers":"100 patients (87% female, mean age 39.6). 41% discontinued at least one medication. SNRI discontinuation 53.8%, CCB 37.5%, beta-blocker 25.6%. CGRP mAb discontinuation: 0%. CGRP mAb users had aOR 2.16 (95% CI 1.16-4.03) for discontinuing other medications.","methodology":"Single-center retrospective cohort at King Chulalongkorn Memorial Hospital, Thailand (2021-2023). Multivariable Cox regression for factors associated with medication discontinuation.","limitations":"Small sample (100 patients). Single center in Thailand. Retrospective. CGRP mAbs may have been given to patients with more severe or refractory migraine. Selection bias. Short follow-up (6 months)."},{"rthcId":"RPEP-13304","title":"Integrating Docking, Dynamics, and Assays to Predict Antimicrobial Peptide Interactions with Mycolic Acid Membranes in Mycobacterium tuberculosis.","authors":"Roque-Borda, Cesar Augusto; Ramirez Delgado, Oswaldo Julio; Duran Gleriani Primo, Laura Maria; Dyhr, Emma; Sæbø, Ingvill Pedersen; Helgesen, Emily; Booth, James; Franzyk, Henrik; Hansen, Paul R; Morales-Navarrete, Hernan; de la Torre, Beatriz G; Albericio, Fernando; Perdigão, João; Pavan, Fernando Rogério","year":2025,"journal":"ACS measurement science au, 5(6), 981-1000","doi":"10.1021/acsmeasuresciau.5c00126","pmid":"41425329","tags":["antimicrobial-peptides","computational-peptide-design","preclinical-research"],"studyType":"computational","evidenceStrength":"low","keyFinding":"A tryptophan-modified amphibian antimicrobial peptide (W-B1CTcu5) showed potent activity against M. tuberculosis (MIC 3.2 micrograms/mL) with strong membrane interaction and multitarget binding, though hemolytic toxicity remains a concern.","whyItMatters":"This study combines lab testing with molecular simulations to understand why some peptide modifications improve TB-killing ability. The approach could accelerate design of less toxic anti-TB peptides.","specificNumbers":"W-B1CTcu5 MIC = 3.2 micrograms/mL against M. tuberculosis. Targets MspA, CpnT, and Ag85B proteins. Low RMSD and residue fluctuation correlated with antimicrobial activity. Hemolytic activity noted.","methodology":"Comparative evaluation of four B1CTcu5 analogs. Experimental MIC testing against MTB. Molecular dynamics simulations of membrane interaction. Docking against key MTB proteins.","limitations":"Hemolytic toxicity limits clinical potential. In vitro activity only. Simulations may not fully predict in vivo behavior. Single parent peptide scaffold. No animal testing."},{"rthcId":"RPEP-13305","title":"Peptide-Based Strategies Against Mycobacterium tuberculosis Covering Immunomodulation, Vaccines, Synergistic Therapy, and Nanodelivery.","authors":"Roque-Borda, Cesar Augusto; Vishwakarma, Subham Kumar; Ramirez Delgado, Oswaldo Julio; de Souza Rodrigues, Heitor Leocadio; Primo, Laura M D; Campos, Isabella Cardeal; de Lima, Tulio Spina; Perdigão, João; Pavan, Fernando Rogério","year":2025,"journal":"Pharmaceuticals (Basel, Switzerland), 18(10)","doi":"10.3390/ph18101440","pmid":"41155557","tags":["antimicrobial-peptides","peptide-vaccines","drug-delivery-systems"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Peptide-based strategies against tuberculosis span four areas: vitamin D-cathelicidin immune activation, peptide vaccines, synergistic combinations with standard antibiotics, and nanocarrier-based pulmonary delivery systems.","whyItMatters":"Drug-resistant TB is a growing crisis. Antimicrobial peptides offer multiple attack angles: boosting the immune system, serving as vaccines, enhancing existing drugs, and being delivered directly to infected lungs.","specificNumbers":"Not specified. Reviews cathelicidin LL-37, various peptide vaccine candidates, combination therapy data, and nanocarrier/inhalable delivery systems.","methodology":"Comprehensive review covering four axes of peptide-based anti-TB innovation: host-directed therapy, peptide vaccines, drug synergy, and delivery technology.","limitations":"Review article. Most evidence preclinical. Clinical translation of peptide-based TB therapies remains early-stage. Regulatory pathways for peptide therapeutics in TB not established."},{"rthcId":"RPEP-13306","title":"Repositioning Antimicrobial Peptides Against WHO-Priority Fungi.","authors":"Roque-Borda, Cesar Augusto; Medina-Alarcón, Kaila Petronila; Gonçalves Pereira, João Paulo Soler; Sevilhano, Thais Cristina Dos Anjos; Aguilar-Morón, Brigitte; Díaz-Cárdenas, Fernando; da Cruz, Lucas Silva; Xavier-Júnior, Francisco Humberto; Vicente, Eduardo Festozo; Perdigão, João; de la Torre, Beatriz G; Albericio, Fernando; Pavan, Fernando Rogério","year":2025,"journal":"Advanced science (Weinheim, Baden-Wurttemberg, Germany), 12(37), e09567","doi":"10.1002/advs.202509567","pmid":"40884276","tags":["antimicrobial-peptides","peptide-engineering","drug-development-pipeline"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Antimicrobial peptides show broad-spectrum activity against WHO-priority fungal pathogens including C. auris, A. fumigatus, and C. albicans. Peptide engineering strategies like cyclization, PEGylation, and nanoparticle conjugation improve their drug-like properties.","whyItMatters":"Fungal infections kill 1.5 million people yearly with only 4 drug classes available. AMPs offer fundamentally different mechanisms that are less prone to resistance, and engineering advances are solving their traditional weaknesses.","specificNumbers":"Focus on C. auris, A. fumigatus, C. neoformans, and C. albicans. Strategies: hybridization, cyclization, PEGylation, nanoparticle conjugation. ML and deep learning tools for rational design discussed.","methodology":"In-depth review of AMP-based antifungal strategies integrating structure-activity relationships, molecular engineering, delivery systems, and computational design approaches.","limitations":"Review article. Most AMP data from in vitro studies. Clinical translation challenging due to formulation, regulatory, and development pipeline hurdles. No approved AMP antifungals yet."},{"rthcId":"RPEP-13307","title":"Anti-inflammatory properties of GLP-1 receptor agonists and other ancillary benefits from a pharmacological perspective.","authors":"Ros-Madrid, Inmaculada; Cano-Mármol, Rosario Paloma; Ferrer-Gomez, Mercedes; Ramos-Molina, Bruno","year":2025,"journal":"Canadian journal of physiology and pharmacology, 103(12), 369-377","doi":"10.1139/cjpp-2025-0148","pmid":"41086442","tags":["glp-1-receptor-agonists","immune-modulation","cardiovascular-outcomes","neurological-applications","liver-disease","kidney-disease"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"GLP-1 receptor agonists exert broad anti-inflammatory effects across metabolic, cardiovascular, liver, kidney, and brain diseases by inhibiting NF-kB signaling, reducing cytokines, and modulating macrophage and microglial activity.","whyItMatters":"Chronic inflammation underlies most diseases where GLP-1 drugs show benefit. Understanding that anti-inflammatory action is a unifying mechanism explains why these drugs help so many different conditions beyond diabetes.","specificNumbers":"Not specified. Reviews NF-kB inhibition, cytokine reduction, macrophage modulation, and microglial effects across diabetes, obesity, MASLD, CVD, kidney disease, and neurodegenerative conditions.","methodology":"Pharmacological narrative review of GLP-1 RA anti-inflammatory mechanisms across organ systems. Covers both direct and indirect pathways.","limitations":"Narrative review. Much evidence from preclinical models. Relative contributions of anti-inflammatory vs. metabolic effects difficult to separate in humans. Mechanisms may differ by organ system."},{"rthcId":"RPEP-13308","title":"Stimuli-Responsive Hydrogels from Liquid-Liquid Phase Separations of FUS-Derived Peptides.","authors":"Rosa, Elisabetta; Pizzella, Mariantonietta; Cimmino, Luca; Castelletto, Valeria; Hamley, Ian W; Vitagliano, Luigi; De Simone, Alfonso; Accardo, Antonella","year":2025,"journal":"ACS applied materials & interfaces, 17(40), 55981-55993","doi":"10.1021/acsami.5c15249","pmid":"40990389","tags":["peptide-engineering","drug-delivery-systems"],"studyType":"laboratory","evidenceStrength":"low","keyFinding":"Peptides derived from the FUS protein form stimuli-responsive hydrogels that release drugs at 40 degrees C, controlled by engineered mutations that tune mechanical and thermal properties.","whyItMatters":"Smart materials that release drugs only when heated to fever-like temperatures could enable targeted delivery to inflamed tissues or tumors.","specificNumbers":"Drug release efficient at 40 degrees C. LARKS peptide building blocks used. Point mutations modulated mechanical properties and temperature stability.","methodology":"Characterization of multi-LARKS peptide phase separation and hydrogel formation. Rheology for mechanical properties. Drug release assays at different temperatures. Rational mutagenesis for property tuning.","limitations":"In vitro characterization only. No in vivo testing. Drug loading capacity and release kinetics not optimized. Biocompatibility not fully assessed. Single drug tested."},{"rthcId":"RPEP-13309","title":"Evaluation of cationic peptide-based nanogels as delivery systems for negatively charged molecules: a formulative study.","authors":"Rosa, Mariangela; Rosa, Elisabetta; Castelletto, Valeria; Hamley, Ian W; Morelli, Giancarlo; Accardo, Antonella; Diaferia, Carlo","year":2025,"journal":"Scientific reports, 15(1), 36875","doi":"10.1038/s41598-025-20945-3","pmid":"41125734","tags":["peptide-engineering","drug-delivery-systems"],"studyType":"laboratory","evidenceStrength":"low","keyFinding":"Cationic peptide nanogels made from Fmoc-diphenylalanine with amphiphilic cationic peptides successfully encapsulated and released anionic molecules with good cytocompatibility.","whyItMatters":"Delivering negatively charged drugs (like nucleic acids) requires positively charged carriers. These peptide-based nanogels offer a biocompatible alternative to synthetic polymers for drug delivery.","specificNumbers":"Fmoc-FF/C16-(GK)3 and Fmoc-FF/C18-(GK)3 formulations tested. Characterized by DLS, CD, FT-IR, and SAXS. AlexaFluor 430 used as model anionic compound. Good cytocompatibility demonstrated.","methodology":"Formulation development using Fmoc-diphenylalanine with cationic amphiphilic peptides. Colloidal stabilization with TWEEN 80 and SPAN 80. Multiple encapsulation vs. adsorption routes compared. In vitro release and cytocompatibility.","limitations":"Model compound only, not a real therapeutic. In vitro characterization. No in vivo testing. Shelf stability limited. Optimization of drug loading not completed."},{"rthcId":"RPEP-13310","title":"Reduction of opioid and barbiturate use following initiation of rimegepant for migraine in the United States.","authors":"Rosen, Noah; Jenkins, Aaron; Hygge Blakeman, Karin; Dai, Feng; Abraham, Lucy; Leroue, Chelsea; Brown, Josh","year":2025,"journal":"Headache","doi":"10.1111/head.15004","pmid":"40650461","tags":["cgrp-peptides","cgrp-receptor-antagonists","migraine","substance-use-and-addiction"],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"Starting rimegepant for migraine was associated with significant reductions in opioid and barbiturate use. 38% of opioid users and 48% of butalbital users completely stopped these medications within 6 months.","whyItMatters":"Opioids and barbiturates are frequently prescribed for migraine despite guideline warnings. Introducing a migraine-specific treatment like rimegepant can pull patients off these harmful medications.","specificNumbers":"1,928 opioid users: fills 2 to 1, MME 25 to 14 (p < 0.001), 38.4% discontinued. 873 butalbital users: fills 2 to 1, mg 200 to 25 (p < 0.001), 48.3% discontinued. Reductions also in preventive treatment users and problematic opioid use subgroup.","methodology":"Retrospective cohort using IQVIA PharMetrics Plus claims data (Sept 2019 to March 2023). Pre-post comparison 180 days before and after rimegepant initiation. Fill quantity of 8 tablets indicated acute treatment.","limitations":"Pre-post design without control group. Regression to the mean possible. Claims data cannot confirm actual medication use. Rimegepant users may be more motivated to reduce opioids. No randomization."},{"rthcId":"RPEP-13311","title":"Orforglipron, an oral non-peptide glucagon-like peptide-1 receptor agonist, improves markers of β-cell function and insulin sensitivity in type 2 diabetes.","authors":"Rosenstock, Julio; Robins, Deborah A; Duffin, Kevin L; Wilson, Jonathan M; Lin, Yanzhu; Banerjee, Hiya; Eyde, Sarah; Kazda, Christof; Konig, Manige; Mather, Kieren J","year":2025,"journal":"Diabetes, obesity & metabolism, 27(11), 6314-6322","doi":"10.1111/dom.70022","pmid":"40808573","tags":["glp-1-receptor-agonists","oral-peptide-delivery","type-2-diabetes","beta-cell-function","drug-development-pipeline"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"Orforglipron, an oral non-peptide GLP-1 agonist, improved beta cell function markers by up to 132% and insulin sensitivity in type 2 diabetes patients, with effects exceeding those of injectable dulaglutide.","whyItMatters":"Orforglipron could make GLP-1 therapy accessible as a daily pill rather than an injection. It not only controls blood sugar but appears to improve the underlying pancreatic and metabolic dysfunction driving type 2 diabetes.","specificNumbers":"378 participants. HOMA-B increased up to 123% (C-peptide) and 132% (insulin) at doses of 12 mg and higher by week 4. HOMA-IR decreased up to 16-23% by week 26. Greater HOMA-B increases than dulaglutide 1.5 mg. Proinsulin/insulin ratio improved. 26-week study.","methodology":"Exploratory analysis of a 26-week phase 2 RCT. Orforglipron 3, 12, 24, 36, or 45 mg daily vs. dulaglutide 1.5 mg weekly vs. placebo. Beta cell function and insulin sensitivity biomarkers assessed.","limitations":"Exploratory post-hoc analysis. Phase 2, not powered for beta cell endpoints. 26-week duration. Cannot determine if beta cell improvements are sustained long-term. Dulaglutide comparison at only one dose."},{"rthcId":"RPEP-13312","title":"Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist, in Early Type 2 Diabetes.","authors":"Rosenstock, Julio; Hsia, Stanley; Nevarez Ruiz, Luis; Eyde, Sarah; Cox, David; Wu, Wen-Shuo; Liu, Rong; Li, Jianghao; Fernández Landó, Laura; Denning, Max; Ludwig, Lisa; Chen, Yanyun","year":2025,"journal":"The New England journal of medicine, 393(11), 1065-1076","doi":"10.1056/NEJMoa2505669","pmid":"40544435","tags":["glp-1-receptor-agonists","oral-peptide-delivery","type-2-diabetes","drug-development-pipeline"],"studyType":"clinical-trial","evidenceStrength":"high","keyFinding":"Orforglipron, an oral non-peptide GLP-1 agonist, reduced HbA1c by up to 1.48 percentage points and body weight by up to 7.6% in early type 2 diabetes over 40 weeks in the ACHIEVE-1 phase 3 trial.","whyItMatters":"This is the first phase 3 trial confirming that a non-injectable, non-peptide GLP-1 drug can produce clinically meaningful blood sugar and weight improvements. It could dramatically expand access to GLP-1 therapy by eliminating the need for injections.","specificNumbers":"559 participants, mean baseline HbA1c 8.0%. HbA1c change: -1.24% (3 mg), -1.47% (12 mg), -1.48% (36 mg) vs. -0.41% (placebo). All p < 0.001. Weight: -4.5% (3 mg), -5.8% (12 mg), -7.6% (36 mg) vs. -1.7% (placebo). Mean HbA1c at 40 weeks: 6.5-6.7%. Discontinuation 4.4-7.8% vs 1.4% placebo.","methodology":"Phase 3, double-blind, placebo-controlled RCT (ACHIEVE-1, NCT05971940). 1:1:1:1 randomization to orforglipron 3, 12, or 36 mg or placebo daily for 40 weeks. Primary endpoint: HbA1c change.","limitations":"No active comparator (injectable GLP-1 RA or oral semaglutide). 40-week duration. Patients with early T2D on diet/exercise only; may not represent broader population. GI adverse events higher with orforglipron."},{"rthcId":"RPEP-13313","title":"The prognostic value of N-terminal pro-B-type natriuretic peptide in patients with severe aortic stenosis and preserved ejection fraction.","authors":"Rosenzveig, Akiva; Ramu, Shivabalan Kathavarayan; Agrawal, Ankit; Prasad, Rohan; Khuttan, Akhilesh; Lomaia, Tamari; Besir, Besir; Rajendran, Judah; Badwan, Osamah; Yun, James; Popovic, Zoran; Reed, Grant; Puri, Rishi; Krishnaswamy, Amar; Harb, Serge; Kapadia, Samir R","year":2025,"journal":"Progress in cardiovascular diseases","doi":"10.1016/j.pcad.2025.11.008","pmid":"41352472","tags":["natriuretic-peptides","cardiovascular-outcomes","biomarkers-and-diagnostics"],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"NT-proBNP above 802 pg/mL predicted increased mortality, heart failure hospitalizations, and longer hospital stays in severe aortic stenosis patients with preserved ejection fraction undergoing TAVR.","whyItMatters":"Risk stratification before heart valve replacement is challenging in patients with preserved ejection fraction. NT-proBNP can detect hidden diastolic dysfunction and predict who will do poorly after the procedure.","specificNumbers":"1,594 patients (784 with complete DD data). NT-proBNP cutoff: 802 pg/mL (sensitivity 62.3%, specificity 54.1%). Higher tertiles: NYHA III/IV 65.7-82.5%, LAVi 37.61-50.14 mL/m2. NT-proBNP >802: increased mortality, HF hospitalizations, longer stays. Cox OR 1.645 (95% CI 1.244-2.174).","methodology":"Retrospective study at Cleveland Clinic (2016-2020). Pre- and post-TAVR NT-proBNP, clinical, and echocardiographic data. DD classified by E/e', TR velocity, and LAVi. Youden Index for optimal cutoff. Kaplan-Meier and Cox regression.","limitations":"Retrospective single center. NT-proBNP sensitivity and specificity moderate (62%/54%). DD classification incomplete in many patients (784 of 1,594). Pre-procedural assessment only. Cannot account for all confounders."},{"rthcId":"RPEP-13314","title":"Effects of Semaglutide With or Without Concomitant Mineralocorticoid Receptor Antagonist Use in Participants With Type 2 Diabetes and Chronic Kidney Disease: A FLOW Trial Prespecified Secondary Analysis.","authors":"Rossing, Peter; Bakris, George; Perkovic, Vlado; Pratley, Richard; Tuttle, Katherine R; Mahaffey, Kenneth W; Idorn, Thomas; Belmar, Nicolas; Bosch-Traberg, Heidrun; Rasmussen, Søren; Busch, Robert S; Schmieder, Ronald E; Gillard, Pieter; Mann, Johannes F E","year":2025,"journal":"Diabetes care, 48(11), 1878-1887","doi":"10.2337/dc25-0472","pmid":"40730031","tags":["glp1-receptor-agonists","semaglutide","kidney-disease","cardiovascular-outcomes","type-2-diabetes"],"studyType":"randomized controlled trial (secondary analysis)","evidenceStrength":"strong","keyFinding":"Semaglutide reduced major kidney events by 49% in people taking MRAs and 21% in those not taking them. Benefits held for heart events and death in both groups.","whyItMatters":"Many people with type 2 diabetes and kidney disease already take MRAs. This shows semaglutide adds kidney and heart protection on top of that existing treatment.","specificNumbers":"49% kidney event reduction in MRA users (HR 0.51, 95% CI 0.30-0.86); 21% reduction in non-MRA users (HR 0.79, 95% CI 0.68-0.92); 33% albuminuria reduction in non-MRA users; n=3,533","methodology":"Prespecified secondary analysis of the FLOW randomized trial. Participants got weekly subcutaneous semaglutide 1.0 mg or placebo. Outcomes compared by baseline MRA use with hazard ratios and interaction p-values.","limitations":"MRA subgroup was small (n=257). Finerenone was not available during recruitment. Interaction tests were not statistically significant, so subgroup differences may be due to chance."},{"rthcId":"RPEP-13315","title":"Once-weekly semaglutide versus placebo for the treatment of type 2 diabetes and chronic kidney disease in Denmark: A long-term cost-effectiveness analysis based on FLOW.","authors":"Rossing, Peter; Lindhardt, Morten; Tikkanen, Christian Klyver; Menon, Jyothi; Cattin, Juliette; Hunt, Barnaby; Malkin, Samuel J P; Chubb, Barrie; Damgaard, Tina; Borg, Rikke","year":2025,"journal":"Cardiovascular diabetology, 25(1), 32","doi":"10.1186/s12933-025-03002-1","pmid":"41422027","tags":["glp1-receptor-agonists","semaglutide","kidney-disease","type-2-diabetes","health-economics"],"studyType":"cost-effectiveness analysis","evidenceStrength":"moderate","keyFinding":"Adding semaglutide to standard care saved money and added 0.60 quality-adjusted life years per person in Denmark for people with type 2 diabetes and kidney disease.","whyItMatters":"Showing a drug both improves health and saves money strengthens the case for wider insurance coverage and clinical adoption.","specificNumbers":"0.60 QALYs gained; DKK 6,068 saved per person in full population; 0.44 QALYs gained with SGLT-2i co-use; ICER DKK 19,167/QALY in SGLT-2i users","methodology":"Lifetime cost-effectiveness modeling using the PRIME T2D Model. Baseline characteristics and treatment effects from the FLOW trial. Denmark-specific costs in 2023 Danish kroner.","limitations":"Model-based projections rely on assumptions about long-term outcomes. Results specific to the Danish healthcare setting. Extrapolation beyond trial duration adds uncertainty."},{"rthcId":"RPEP-13316","title":"Focus on therapeutic peptides and their delivery.","authors":"Rosson, E; Lux, F; David, L; Godfrin, Y; Tillement, O; Thomas, E","year":2025,"journal":"International journal of pharmaceutics, 675, 125555","doi":"10.1016/j.ijpharm.2025.125555","pmid":"40194730","tags":["peptide-drug-design","drug-delivery-systems","pharmacokinetics","bioavailability"],"studyType":"narrative review","evidenceStrength":"low (review of field)","keyFinding":"About 100 peptide drugs have reached clinical approval, with nearly half approved in the past 20 years. The global market may exceed $50 billion.","whyItMatters":"Peptides sit between small molecules and large biologics, offering a unique balance of specificity, lower toxicity, and simpler manufacturing that drives rapid growth in drug development.","specificNumbers":"~100 approved peptide therapeutics; nearly 50% approved in last 20 years; market projected >$50 billion by 2024","methodology":"Narrative literature review covering therapeutic peptides, parenteral administration routes, and novel delivery systems.","limitations":"Narrative review without systematic search methodology. Market projections may vary by source. Does not cover every approved peptide individually."},{"rthcId":"RPEP-13317","title":"Vitamin D-inducible antimicrobial peptide LL-37 binds SARS-CoV-2 Spike and accessory proteins ORF7a and ORF8.","authors":"Roth, Annika; Lütke, Steffen; Mörgelin, Matthias; Meinberger, Denise; Hermes, Gabriele; Sengle, Gerhard; Koch, Manuel; Drexelius, Marco; Gebauer, Jan; Neundorf, Ines; Elezagic, Dzemal; Paulsson, Mats; Streichert, Thomas; Klatt, Andreas R","year":2025,"journal":"Frontiers in cellular and infection microbiology, 15, 1671738","doi":"10.3389/fcimb.2025.1671738","pmid":"41064641","tags":["antimicrobial-peptides","ll-37-cathelicidin","infectious-disease","immune-modulation"],"studyType":"laboratory study","evidenceStrength":"low (in vitro)","keyFinding":"The human antimicrobial peptide LL-37 bound the SARS-CoV-2 Spike protein and blocked its attachment to the ACE2 receptor in lab tests. Up to seven LL-37 molecules surrounded each Spike protein.","whyItMatters":"LL-37 is naturally produced in the body when vitamin D levels are adequate. Understanding how it blocks viral entry could inform new antiviral strategies.","specificNumbers":"Up to 7 LL-37 molecules per Spike protein; binding confirmed to Spike, ORF7a, and ORF8","methodology":"In vitro study using surface plasmon resonance to measure binding and negative-stain electron microscopy to visualize LL-37-Spike complexes.","limitations":"All results are from lab-based experiments. Binding in a test tube does not guarantee the same effect in living tissue. No animal or human data included."},{"rthcId":"RPEP-13318","title":"The use of an automatic remote weight management system to track treatment response, identified drugs supply shortage and its consequences: A pilot study.","authors":"Roth, Idan; Cohen, Ohad","year":2025,"journal":"Digital health, 11, 20552076251314090","doi":"10.1177/20552076251314090","pmid":"39866891","tags":["glp1-receptor-agonists","semaglutide","obesity","digital-health"],"studyType":"pilot study","evidenceStrength":"low","keyFinding":"A remote weight monitoring system tracked 11 patients on semaglutide for 12 months and detected when a drug supply shortage caused weight regain of 13 kg across the group.","whyItMatters":"Automatic daily weight tracking can spot problems like drug shortages early, giving clinicians a chance to intervene before patients lose progress.","specificNumbers":"11 participants; 85 kg cumulative weight loss before shortage; 13 kg cumulative regain after shortage; 12-month monitoring; 0% attrition","methodology":"Prospective pilot study using cloud-based Wi-Fi smart scales to collect daily weight data over 12 months during semaglutide treatment.","limitations":"Very small sample size (n=11). No control group. Single-site study. Supply shortage was an unplanned event, not a controlled variable."},{"rthcId":"RPEP-13319","title":"Incretin-Based Drugs and the Incidence of Endometrial Cancer Among People with Type 2 Diabetes: Active Comparator New-User Design.","authors":"Rothman, Sonny M; Yin, Hui; Yu, Oriana H Y; Pollak, Michael; Azoulay, Laurent","year":2025,"journal":"Drug safety, 48(9), 1023-1033","doi":"10.1007/s40264-025-01551-8","pmid":"40347221","tags":["glp1-receptor-agonists","cancer-risk","type-2-diabetes","safety-profile","dpp4-inhibitors"],"studyType":"observational study (active comparator new-user design)","evidenceStrength":"moderate","keyFinding":"GLP-1 receptor agonist use for over 2 years was linked to a 2.47 times higher rate of endometrial cancer compared to sulfonylureas in women with type 2 diabetes.","whyItMatters":"Prior research suggested GLP-1 drugs might lower cancer risk. This large UK study found the opposite for endometrial cancer with longer use, raising questions that need further investigation.","specificNumbers":"9,239 GLP-1 RA users vs 80,086 sulfonylurea users; HR 2.47 (95% CI 1.37-4.43) for >2yr GLP-1 RA use; HR 2.26 (95% CI 1.06-4.82) for exenatide; HR 1.63 (95% CI 1.14-2.33) for >2yr DPP-4i use","methodology":"Population-based active comparator new-user cohort study using UK CPRD data. Propensity score fine stratification weighted Cox models for hazard ratios.","limitations":"Observational design cannot establish causation. Possible residual confounding. Endometrial cancer events were relatively rare. Duration-response analysis has smaller sample sizes in longer-use groups."},{"rthcId":"RPEP-13320","title":"Diagnostic accuracy and rapid testing of a novel acute heart failure biomarker: A laboratory evaluation and comparison with natriuretic peptides.","authors":"Rouet, Kevin; Rouet, Philippe; Koukoui, François; Galinier, Michel","year":2025,"journal":"Annals of clinical biochemistry, 45632251378035","doi":"10.1177/00045632251378035","pmid":"40877033","tags":["biomarkers","cardiovascular-outcomes","diagnostics"],"studyType":"diagnostic accuracy study","evidenceStrength":"moderate","keyFinding":"A new biomarker called FILDARIA distinguished acute heart failure from non-cardiac shortness of breath with high accuracy and worked with a rapid point-of-care test.","whyItMatters":"Current heart failure diagnosis using BNP and echocardiography takes time. A fast, accurate blood test could speed up emergency room decisions.","specificNumbers":"235 patients: 91 acute heart failure, 55 chronic heart failure, 89 non-cardiac dyspnea; BNP 905 vs 58 pg/mL in AHF vs NCD","methodology":"Single-center diagnostic study comparing FILDARIA and BNP levels across three patient groups using ELISA and lateral flow assays. Diagnosis confirmed by echocardiography.","limitations":"Single-center study with modest sample size. Echocardiography as reference standard may miss some cases. Point-of-care test needs validation in larger multicenter trials."},{"rthcId":"RPEP-13321","title":"Rational design of cyclic peptides, with an emphasis on bicyclic peptides.","authors":"Rowland, Catherine E; Bezerra, Gustavo Arruda; Skynner, Michael J","year":2025,"journal":"Current opinion in structural biology, 92, 103025","doi":"10.1016/j.sbi.2025.103025","pmid":"40068542","tags":["peptide-drug-design","drug-delivery-systems","structure-activity-relationships"],"studyType":"narrative review","evidenceStrength":"low (review of field)","keyFinding":"Cyclic and bicyclic peptides offer better stability and bioavailability than linear peptides while keeping the ability to block protein-protein interactions that small molecules cannot reach.","whyItMatters":"Protein-protein interactions drive many diseases but are hard to drug. Cyclic peptides fill a gap between small molecules and large biologics as a new class of therapeutics.","specificNumbers":"N/A (review of design methodologies)","methodology":"Narrative review of recent literature on macrocyclic and bicyclic peptide design, including computational, structure-guided, and phage display approaches.","limitations":"Narrative review without systematic methodology. Focuses on design principles rather than clinical outcomes. May not cover all recent developments equally."},{"rthcId":"RPEP-13322","title":"From metabolism to mind: The expanding role of the GLP-1 receptor in neurotherapeutics.","authors":"Roy, Akash; Dawson, Valina L; Dawson, Ted M","year":2025,"journal":"Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 22(5), e00712","doi":"10.1016/j.neurot.2025.e00712","pmid":"40738791","tags":["glp1-receptor-agonists","neuroprotection","neurological-disorders","tirzepatide"],"studyType":"narrative review","evidenceStrength":"low (review of field)","keyFinding":"GLP-1 receptor agonists show neuroprotective effects in animal models of Alzheimers, Parkinsons, MS, and ALS, but human trial results have been mixed.","whyItMatters":"Repurposing GLP-1 drugs for brain diseases could help millions of patients if clinical trials can confirm the benefits seen in animal studies.","specificNumbers":"N/A (narrative review of preclinical and clinical evidence across multiple diseases)","methodology":"Narrative review of preclinical and clinical studies on GLP-1 receptor agonists in neurological disorders including AD, PD, MS, and ALS.","limitations":"Narrative review without systematic search. Clinical trial results are heterogeneous. Most strong evidence comes from animal models, which often do not translate directly to humans."},{"rthcId":"RPEP-13323","title":"Gastrointestinal tolerability and weight reduction associated with tirzepatide in adults with obesity or overweight with and without type 2 diabetes in the SURMOUNT-1 to -4 trials.","authors":"Rubino, Domenica M; Pedersen, Sue D; Connery, Lisa; Cao, Dachuang; Chigutsa, Farai; Stefanski, Adam; Fraseur Brumm, Julia; Griffin, Ryan; Gerber, Claire","year":2025,"journal":"Diabetes, obesity & metabolism, 27(4), 1826-1835","doi":"10.1111/dom.16176","pmid":"39789843","tags":["tirzepatide","obesity","gastrointestinal-effects","weight-management","safety-profile"],"studyType":"post hoc analysis of randomized controlled trials","evidenceStrength":"strong","keyFinding":"GI side effects like nausea and vomiting contributed at most 3.1% of the total weight loss seen with tirzepatide across the SURMOUNT trials.","whyItMatters":"Some critics suggested GLP-1 drugs only work because they make people feel sick. This analysis shows tirzepatide produces nearly the same weight loss whether or not patients have GI symptoms.","specificNumbers":"GI AEs in 27.8-72.8% of tirzepatide vs 12.2-32.5% of placebo; 1.0-10.5% discontinued due to GI AEs; GI mediated up to 3.1% of weight loss","methodology":"Post hoc analysis pooling data from SURMOUNT-1 through -4 Phase 3 trials. Compared weight change by GI symptom status. Mediation analysis quantified GI contribution to weight loss.","limitations":"Post hoc analysis, not prespecified. GI symptoms were self-reported. Mediation analysis assumes causal pathways that may not fully hold. Pooling across trials with different populations."},{"rthcId":"RPEP-13324","title":"Weight management treatment in obesity.","authors":"Rubio-Herrera, Miguel A; Mera-Carreiro, Sara","year":2025,"journal":"Medicina clinica, 165(5), 107152","doi":"10.1016/j.medcli.2025.107152","pmid":"40865172","tags":["obesity","glp1-receptor-agonists","semaglutide","tirzepatide","weight-management"],"studyType":"narrative review","evidenceStrength":"low (review of field)","keyFinding":"Second-generation weight loss drugs now achieve 15-25% body weight reduction, approaching bariatric surgery results. Combinations like CagriSema and retatrutide may push results even higher.","whyItMatters":"For the first time, medications are closing the gap with surgery for obesity treatment, expanding options for the millions who cannot or choose not to have surgery.","specificNumbers":"GLP-1 RAs: 15-17% weight loss; tirzepatide: up to 22.5%; CagriSema: cagrilintide 2.4 mg + semaglutide 2.4 mg; range of 15-25% for second-generation drugs","methodology":"Narrative review of marketed and pipeline anti-obesity drugs including GLP-1 RAs, dual agonists, and triple agonists.","limitations":"Narrative review without systematic search. Some drugs discussed are still in clinical trials with incomplete data. Long-term durability data are limited for newer agents."},{"rthcId":"RPEP-13325","title":"Splanchnic and Leg Glucagon Metabolism in Healthy Individuals and Those With Type 1 Diabetes: First-in-Human Study Using [13C9,15N1]Glucagon.","authors":"Ruchi, F N U; Schiavon, Michele; Yadav, Yogesh; Dalla Man, Chiara; Cobelli, Claudio; Pandey, Akhilesh; Wilkins, Luke; Basu, Rita; Basu, Ananda","year":2025,"journal":"Diabetes, 74(8), 1342-1354","doi":"10.2337/db24-1064","pmid":"40445879","tags":["glucagon","type-1-diabetes","pharmacokinetics","hormone-regulation"],"studyType":"first-in-human physiological study","evidenceStrength":"moderate","keyFinding":"The liver cleared about 30% of circulating glucagon in both healthy people and those with type 1 diabetes. Leg clearance differed: it dropped as glucagon rose in healthy people but stayed flat in type 1 diabetes.","whyItMatters":"Understanding how the body handles glucagon helps improve dual-hormone insulin pumps and explains how new GLP-1/glucagon drugs affect hormone balance.","specificNumbers":"Liver extraction ~30% in both groups; leg extraction in healthy: 41% to 24% with rising glucagon; leg in T1D: ~27% stable; n=8 healthy, n=6 T1D","methodology":"First-in-human isotope dilution study using novel stable glucagon tracers with splanchnic and leg catheterization. Glucagon infused at escalating rates.","limitations":"Very small sample (n=14 total). Overnight fasted state only. Does not capture post-meal glucagon dynamics. Catheterization studies are technically demanding and hard to replicate at scale."},{"rthcId":"RPEP-13326","title":"Glucagon-Like Peptide-1 Receptor Agonist-Experienced Adults with Type 2 Diabetes Switching to Once-Weekly Semaglutide in a Real-World Setting: SURE Program Post Hoc Analysis.","authors":"Rudofsky, Gottfried; Menzen, Markus; Potier, Louis; Catarig, Andrei-Mircea; Clark, Alice; Priyadarshini, Prachi; Abreu, Cristina","year":2025,"journal":"Advances in therapy, 42(2), 788-800","doi":"10.1007/s12325-024-03000-x","pmid":"39636564","tags":["glp1-receptor-agonists","semaglutide","type-2-diabetes","hba1c","weight-management"],"studyType":"post hoc analysis of observational studies","evidenceStrength":"moderate","keyFinding":"People with type 2 diabetes who switched from another GLP-1 drug to once-weekly semaglutide lost an additional 0.67 percentage points of HbA1c and 3.69 kg of body weight.","whyItMatters":"Patients not responding well to one GLP-1 drug may gain extra benefit by switching to semaglutide rather than abandoning the drug class entirely.","specificNumbers":"651 switchers from 3,505 total SURE participants; -0.67% HbA1c (95% CI -0.74 to -0.60); -3.69 kg body weight (95% CI -3.98 to -3.41)","methodology":"Post hoc analysis of nine SURE program observational studies. Mixed model for repeated measurements analyzed HbA1c and weight changes in GLP-1 RA-experienced patients switching to semaglutide.","limitations":"Post hoc analysis of observational data. No control group of patients staying on prior GLP-1 RA. Regression to the mean may partly explain improvements. Variable follow-up durations."},{"rthcId":"RPEP-13327","title":"Oral Semaglutide Use in Type 2 Diabetes: A Pooled Analysis of Clinical and Patient-Reported Outcomes from Seven PIONEER REAL Prospective Real-World Studies.","authors":"Rudofsky, Gottfried; Amadid, Hanan; Braae, Uffe Christian; Catrina, Sergiu-Bogdan; Kick, Anastas; Mandavya, Kabirdev; Roslind, Klaus; Saravanan, Ponnusamy; van Houtum, William; Jain, Akshay B","year":2025,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 16(1), 73-87","doi":"10.1007/s13300-024-01668-6","pmid":"39535683","tags":["glp1-receptor-agonists","semaglutide","type-2-diabetes","oral-peptide-delivery","hba1c"],"studyType":"pooled analysis of observational studies","evidenceStrength":"moderate","keyFinding":"Oral semaglutide reduced HbA1c by 1.0 percentage point and produced weight loss across all age groups and diabetes durations in real-world practice across seven countries.","whyItMatters":"Clinical trials use strict criteria. This real-world data shows oral semaglutide works broadly in everyday patients, including older adults and those with long-standing diabetes.","specificNumbers":"1,615 participants; -1.0% HbA1c at week 38 (95% CI -1.08 to -0.97); 76% on treatment at end of study; 7 countries","methodology":"Pooled analysis of seven PIONEER REAL prospective, non-interventional, single-arm Phase 4 studies. Outcomes stratified by age, diabetes duration, dose, and baseline characteristics.","limitations":"No control group. Single-arm observational design. Pooling across countries introduces heterogeneity. Patients who discontinued were not tracked for outcomes."},{"rthcId":"RPEP-13328","title":"Real-world safety comparison of liraglutide and semaglutide in weight management: Insights from European pharmacovigilance data.","authors":"Ruggiero, Rosanna; Longo, Miriam; Mascolo, Annamaria; Di Nuzzo, Michela; Laino, Ludovica Vittoria; Caruso, Paola; D'Amato, Rossana; Rafaniello, Concetta; Maiorino, Maria Ida; Esposito, Katherine; Capuano, Annalisa","year":2025,"journal":"European journal of pharmacology, 1004, 178004","doi":"10.1016/j.ejphar.2025.178004","pmid":"40716637","tags":["glp1-receptor-agonists","semaglutide","liraglutide","safety-profile","obesity"],"studyType":"pharmacovigilance study (case-non-case)","evidenceStrength":"moderate","keyFinding":"Liraglutide had higher reporting rates of pancreatitis, gallbladder disorders, and thyroid tumors. Semaglutide had higher rates of vomiting and abdominal pain. Neither showed elevated reports of depression or suicidal thoughts.","whyItMatters":"As millions more people take these drugs for weight loss, understanding the distinct safety profiles of each helps doctors match the right drug to the right patient.","specificNumbers":"27,639 total cases; Jan 2018-Dec 2023; majority female, aged 18-64; 2 gallbladder tumor reports; most AEs non-serious","methodology":"Retrospective case-non-case study using EudraVigilance data. Disproportionality analysis with reporting odds ratios for predefined events of interest reported at least three times.","limitations":"Pharmacovigilance data reflect reporting patterns, not true incidence. Reporting bias and stimulated reporting can distort results. Cannot establish causation. No denominator data for drug exposure."},{"rthcId":"RPEP-13329","title":"pH-responsive polymeric nanoparticles for peptide delivery: Synergistic STING pathway activation enhances tumor immunotherapy.","authors":"Rui, Mengjie; Tang, Haidan; Gao, Lianglai; Hu, Yujiao; Liang, Wenyan; Li, Yinfeng; Feng, Chunlai","year":2025,"journal":"International journal of pharmaceutics: X, 10, 100412","doi":"10.1016/j.ijpx.2025.100412","pmid":"41127047","tags":["peptide-drug-design","drug-delivery-systems","cancer-immunotherapy","nanotechnology"],"studyType":"preclinical study (in vivo/in vitro)","evidenceStrength":"low (animal model)","keyFinding":"pH-responsive nanoparticles carrying a peptide activated the STING immune pathway and shrank tumors in mice more than free peptide, with no major toxicity.","whyItMatters":"Peptide cancer vaccines often break down before reaching tumors. This nanoparticle both protects the peptide and boosts the immune response on its own.","specificNumbers":"Nanoparticle diameter 91.2 +/- 3.5 nm; enhanced IFN-gamma and IL-2 in vitro and in vivo; 4T1 mouse breast tumor model; no significant body weight change","methodology":"Nanoparticles prepared by self-assembly. In vitro: T cell cytotoxicity and IL-2 secretion assays. In vivo: 4T1 tumor-bearing mouse model with IV administration. Measured tumor volume, IFN-gamma, and body weight.","limitations":"Mouse tumor model results often do not translate to humans. Single tumor type tested (4T1 breast). No comparison with other nanocarrier systems. Early-stage preclinical work."},{"rthcId":"RPEP-13330","title":"Effectiveness of liraglutide in the treatment of adolescent obesity.","authors":"Ruiz Pons, Mónica; Gutiérrez Vilar, Marina; García Zurita, Celia; Fuentes Ferrer, Manuel Enrique; Pérez Rodríguez, Alejandra; Rosado Alonso, Cristina","year":2025,"journal":"Anales de pediatria, 103(1), 503856","doi":"10.1016/j.anpede.2025.503856","pmid":"40645873","tags":["glp1-receptor-agonists","liraglutide","obesity","pediatric-studies"],"studyType":"retrospective observational study","evidenceStrength":"moderate","keyFinding":"Adolescents taking liraglutide plus lifestyle changes had a BMI z-score drop of 1.09 versus 0.10 for lifestyle changes alone. Nearly half achieved at least 5% BMI reduction.","whyItMatters":"Treatment options for adolescent obesity are limited. This is among the first real-world studies showing liraglutide is effective in teenagers.","specificNumbers":"62 adolescents (31 per group); BMI z-score: -1.09 vs -0.10 (p=0.001); 48.4% vs 3% achieved 5%+ BMI reduction; 29% vs 1% achieved 10%+ reduction; treatment ~6.9 months; follow-up ~12.5 months","methodology":"Retrospective observational study with matched controls. Anthropometric, cardiovascular, and body composition measured at baseline, end of treatment, and follow-up. ANCOVA and logistic regression for comparisons.","limitations":"Retrospective design with potential selection bias. Small sample size (n=62). Single center in Spain. No randomization. Matching may not account for all confounders."},{"rthcId":"RPEP-13331","title":"Clinical factors influencing the systolic blood pressure benefits of once-weekly semaglutide in patients with type 2 diabetes.","authors":"Ruiz-Sánchez, Jorge Gabriel; Sierra Poyatos, Roberto Miguel; Luiza Luca, Bogdana; Sánchez-Lechuga, Begoña; Modroño Móstoles, Naiara; Montoya Álvarez, Teresa; Meneses, Diego; Sánchez-Lopez, Raquel; Casado Cases, Carlos; Pérez de Arenaza Pozo, Víctor; Vázquez, Clotilde; Cárdenas-Salas, Jersy Jair","year":2025,"journal":"Medicina clinica, 165(6), 107179","doi":"10.1016/j.medcli.2025.107179","pmid":"41014747","tags":["glp1-receptor-agonists","semaglutide","type-2-diabetes","cardiovascular-outcomes","blood-pressure"],"studyType":"sub-analysis of observational study","evidenceStrength":"moderate","keyFinding":"Once-weekly semaglutide lowered systolic blood pressure by 4 mmHg at 6 months in people with type 2 diabetes. The benefit was strongest in those with uncontrolled blood pressure at baseline.","whyItMatters":"High blood pressure is common in type 2 diabetes and drives heart disease risk. Knowing which patients get the most blood pressure benefit from semaglutide helps target treatment.","specificNumbers":"178 patients; -4 mmHg SBP at 6 months, -2 mmHg at 12 months (p=0.014); 79.2% with hypertension; mean age 61; 43.8% female","methodology":"Sub-analysis of the REALSEM-SP observational study. Changes in SBP and DBP analyzed over 12 months. Multivariate analysis identified factors independently associated with SBP reduction.","limitations":"Observational sub-analysis without control group. Modest sample size. Office blood pressure only (no 24-hour monitoring). Blood pressure reduction at 12 months was smaller than at 6 months."},{"rthcId":"RPEP-13332","title":"Semaglutide 2.4 mg Clinical Outcomes in Patients with Obesity or Overweight: A Real-World Retrospective Comparative Cohort Study.","authors":"Ruseva, Aleksandrina; Michalak, Wojciech; Fabricatore, Anthony; Hartaigh, Bríain Ó; Zhao, Zhenxiang; Umashanker, Devika","year":2025,"journal":"Advances in therapy, 42(10), 4993-5009","doi":"10.1007/s12325-025-03320-6","pmid":"40768189","tags":["glp1-receptor-agonists","semaglutide","obesity","weight-management","cardiovascular-outcomes"],"studyType":"retrospective comparative cohort study","evidenceStrength":"moderate","keyFinding":"Semaglutide 2.4 mg produced 15% body weight loss and improved all cardiometabolic markers compared to no obesity medication at 12 months in real-world US practice.","whyItMatters":"This is one of the largest real-world comparative studies showing semaglutide outperforms no treatment across weight, blood pressure, cholesterol, and blood sugar.","specificNumbers":"-15.0% weight loss vs controls; -15.7 kg; -4.2 kg/m2 BMI; -6.7 mmHg SBP; -2.7 mmHg DBP; -0.5% HbA1c; -10.4 mg/dL LDL; -34.3 mg/dL triglycerides; n=8,857 vs 35,428","methodology":"Retrospective observational cohort using US claims and medical records. Propensity score 1:4 matching. Generalized linear models compared 12-month outcomes.","limitations":"Retrospective design with possible residual confounding despite matching. Weight data available for only a subset of patients. No randomization."},{"rthcId":"RPEP-13333","title":"Semaglutide 2.4 mg long-term clinical outcomes in patients with obesity or overweight: a real-world retrospective cohort study in the United States (SCOPE 12 months).","authors":"Ruseva, Aleksandrina; Dabbous, Firas; Ding, Nina; Fabricatore, Anthony; Huse, Samuel; Michalak, Wojciech; Nordstrom, Beth; Ó Hartaigh, Bríain; Zhao, Zhenxiang; Umashanker, Devika","year":2025,"journal":"Postgraduate medicine, 137(3-4), 251-260","doi":"10.1080/00325481.2025.2482274","pmid":"40122077","tags":["glp1-receptor-agonists","semaglutide","obesity","weight-management","cardiovascular-outcomes"],"studyType":"retrospective cohort study","evidenceStrength":"moderate","keyFinding":"US patients on semaglutide 2.4 mg lost 14.5% of body weight at 52 weeks and maintained the loss at 68 weeks, with improvements in blood pressure, HbA1c, and lipids.","whyItMatters":"Extends real-world weight loss data to 68 weeks, showing semaglutide maintains its effect beyond one year in everyday clinical practice.","specificNumbers":"-15.5 kg (-14.5%) at 52 weeks; -15.9 kg (-14.8%) at 68 weeks; -4.8 kg/m2 BMI at 52 wk; -6.3 mmHg SBP; -3.1 mmHg DBP; -0.4% HbA1c; -38.4 mg/dL triglycerides; n=4,424","methodology":"Retrospective cohort using Komodo Health database. Paired t-tests compared baseline to 52-week and 68-week outcomes in patients who remained on treatment.","limitations":"No control group. Only patients who stayed on treatment are included, creating selection bias toward responders. Subset had cardiometabolic data."},{"rthcId":"RPEP-13334","title":"Sustained weight reduction with once-weekly semaglutide: results from a real-world retrospective cohort study in the United States (SCOPE 24 months).","authors":"Ruseva, Aleksandrina; Michalak, Wojciech; Fabricatore, Anthony; Hartaigh, Bríain Ó; Zhao, Zhenxiang; Wang, Julia; Umashanker, Devika","year":2025,"journal":"Current medical research and opinion, 41(11), 2103-2114","doi":"10.1080/03007995.2025.2591464","pmid":"41351543","tags":["glp1-receptor-agonists","semaglutide","obesity","weight-management","cardiovascular-outcomes"],"studyType":"retrospective cohort study","evidenceStrength":"moderate","keyFinding":"Patients on semaglutide for 24 months lost an average of 16.6% of their body weight (17.9 kg) in real-world US practice, with improvements across all cardiometabolic markers.","whyItMatters":"Most real-world weight loss data only cover 6-12 months. This 24-month study shows semaglutide maintains substantial weight loss over two years outside clinical trial settings.","specificNumbers":"630 patients with 24-month data from 2,592 eligible; -17.9 kg (-16.6%) weight loss; -6.0 kg/m2 BMI; mean age 48.6; 77.8% female; all cardiometabolic markers improved (p significant)","methodology":"Retrospective cohort using Komodo Health database. Included adults with obesity or overweight plus at least one obesity-related condition who escalated to and maintained semaglutide 1.7 or 2.4 mg. Paired t-tests for 24-month changes.","limitations":"Retrospective design with potential selection bias toward adherent patients. Only 630 of 2,592 eligible had 24-month data. No control group. Patients who discontinued are not represented in outcomes."},{"rthcId":"RPEP-13335","title":"Advances in Migraine Treatment: A Comprehensive Clinical Review.","authors":"Rushendran, Rapuru; Vellapandian, Chitra","year":2025,"journal":"Current protein & peptide science, 26(6), 422-435","doi":"10.2174/0113892037329429241123095325","pmid":"39810518","tags":["cgrp","neuropeptides","neurological-disorders","drug-delivery-systems"],"studyType":"narrative review","evidenceStrength":"low (review of field)","keyFinding":"Migraine treatment has expanded beyond triptans to include CGRP-targeting monoclonal antibodies, neuromodulation devices, and wearable technology, with precision medicine on the horizon.","whyItMatters":"Migraine affects one in seven people worldwide. This review maps the full treatment landscape from established drugs to emerging gene-based therapies.","specificNumbers":"1 in 7 people worldwide affected; migraine prevalence has increased in recent decades","methodology":"Narrative clinical review of pharmaceutical, device-based, and emerging migraine therapies.","limitations":"Narrative format without systematic methodology. Some discussed therapies are early-stage or not yet approved. Does not quantify comparative efficacy."},{"rthcId":"RPEP-13336","title":"Effectiveness and tolerability of atogepant as preventive treatment in resistant individuals with chronic migraine: Six-month real-world evidence.","authors":"Russo, Antonio; Silvestro, Marcello; Finkelstein, Ian; Seabi, Dineo; Ahlden, Adam; Aamodt, Anne Hege; Caronna, Edoardo; Pozo-Rosich, Patricia; Tronvik, Erling; Sundal, Christina","year":2025,"journal":"Cephalalgia : an international journal of headache, 45(8), 3331024251370608","doi":"10.1177/03331024251370608","pmid":"40874574","tags":["cgrp","neuropeptides","neurological-disorders","safety-profile"],"studyType":"prospective observational study","evidenceStrength":"moderate","keyFinding":"Atogepant 60 mg daily reduced monthly migraine days by 7.1 at 24 weeks in treatment-resistant chronic migraine patients. Even 47% of those who had failed prior CGRP antibodies responded.","whyItMatters":"Patients who fail multiple migraine preventives, including CGRP antibodies, have few options left. This study shows atogepant can still help nearly half of them.","specificNumbers":"100 patients; -7.1 monthly migraine days at 24 wk; 53% achieved 50%+ reduction; 60% converted to episodic; 47% responders among CGRP-mAb failures; constipation 28%, fatigue 16%; median 6 prior treatment failures","methodology":"Prospective, monocentric, real-world study. 100 consecutive patients with chronic migraine and 3+ treatment failures. Atogepant 60 mg daily for 24 weeks. Primary outcomes: change in monthly migraine days and 50% responder rate.","limitations":"Single-center, open-label, no control group. Selection bias possible from consecutive enrollment at a headache center. Socioeconomic status as a predictor may reflect healthcare access rather than biology."},{"rthcId":"RPEP-13337","title":"ForePass outperforms Semaglutide in weight control, glucose metabolism, and gut microbiota in swine.","authors":"Russo, Sara; Proto, Luca; Neto, Manoel Galvao; Angelini, Giulia; Pezzica, Samantha; Carli, Fabrizia; Previti, Elena; Caristo, Maria Emiliana; Bove, Vincenzo; Chakaroun, Rima; Roggiani, Sara; Tremaroli, Valentina; Le Roux, Carel W; Bornstein, Stefan R; Gastaldelli, Amalia; Boskoski, Ivo; Mingrone, Geltrude","year":2025,"journal":"Diabetes, obesity & metabolism, 27(12), 7587-7601","doi":"10.1111/dom.70167","pmid":"41025205","tags":["glp1-receptor-agonists","semaglutide","obesity","gut-microbiome","insulin-signaling"],"studyType":"preclinical study (animal model)","evidenceStrength":"low (animal study)","keyFinding":"A new endoscopic device called ForePass improved insulin sensitivity more than semaglutide in pigs and increased beneficial gut bacteria (Akkermansia muciniphila).","whyItMatters":"If confirmed in humans, a reversible, incision-free endoscopic device could offer an alternative between drug therapy and bariatric surgery for obesity.","specificNumbers":"12 pigs (4 per group); SI: 2.75 vs 1.34 (ForePass vs semaglutide); EGP 46% lower with ForePass vs semaglutide; 40% lower glucose Ra; 30-day study","methodology":"Controlled animal study in growing Landrace pigs. Three groups: ForePass, twice-weekly semaglutide, or sham endoscopy. Oral glucose tolerance test with isotope tracers. Metabolomics and microbiome analysis.","limitations":"Only 4 animals per group. 30-day duration in growing pigs may not reflect chronic disease settings. Pig metabolism differs from human metabolism. No long-term data."},{"rthcId":"RPEP-13338","title":"Semaglutide in the Real World: Attitudes of the Population.","authors":"Rušić, Doris; Durdov, Toni; Jadrijević, Ivona; Šešelja Perišin, Ana; Leskur, Dario; Božić, Joško; Klusmeier, Mila Marie; Bukić, Josipa","year":2025,"journal":"Pharmacy (Basel, Switzerland), 13(5)","doi":"10.3390/pharmacy13050128","pmid":"40981248","tags":["glp1-receptor-agonists","semaglutide","obesity","patient-education"],"studyType":"cross-sectional survey","evidenceStrength":"low","keyFinding":"74% of Croatian survey respondents had heard of Ozempic regardless of whether they had type 2 diabetes. Social media strongly influenced perceptions about weight loss medications.","whyItMatters":"Public awareness of semaglutide has outpaced accurate knowledge about its uses and risks, creating potential for misuse and unmet safety awareness.","specificNumbers":"290 participants; 83.8% female; 73.8% heard of Ozempic; 75% without healthcare family unaware of side effects; 23.4% knew someone taking it","methodology":"Cross-sectional population survey with descriptive statistics and chi-square tests for group comparisons.","limitations":"Convenience sample with 84% female respondents, limiting generalizability. Single-country study. Self-reported knowledge may not reflect actual understanding."},{"rthcId":"RPEP-13339","title":"New drugs for the treatment of obesity: do we need approaches to preserve muscle mass?","authors":"Ryan, Donna H","year":2025,"journal":"Reviews in endocrine & metabolic disorders, 26(5), 805-813","doi":"10.1007/s11154-025-09967-4","pmid":"40320499","tags":["glp1-receptor-agonists","semaglutide","tirzepatide","obesity","muscle-wasting"],"studyType":"narrative review","evidenceStrength":"low (review of field)","keyFinding":"Semaglutide causes about 45% of weight loss from lean mass, while tirzepatide causes about 25%. Myostatin-activin pathway inhibitors like bimagrumab may help preserve muscle during treatment.","whyItMatters":"As GLP-1 drugs are used long-term in older patients, losing too much muscle and bone could lead to frailty and falls, undermining the health gains from weight loss.","specificNumbers":"Semaglutide: ~45% lean mass loss; tirzepatide: ~25% lean mass loss; muscle/bone loss accelerates past age 60","methodology":"Narrative review of lean mass preservation during anti-obesity pharmacotherapy, covering current drugs and pipeline combination approaches.","limitations":"Narrative format without systematic search. Lean mass percentages cited may vary by study and measurement method. MAPi drugs are still investigational."},{"rthcId":"RPEP-13340","title":"The potential role of GLP-1 receptor agonists in osteoarthritis.","authors":"Ryan, Mackenzie; Megyeri, Saige; Nuffer, Wes; Trujillo, Jennifer M","year":2025,"journal":"Pharmacotherapy, 45(3), 177-186","doi":"10.1002/phar.70005","pmid":"39980227","tags":["glp1-receptor-agonists","semaglutide","inflammation","musculoskeletal"],"studyType":"narrative review","evidenceStrength":"low (review of field)","keyFinding":"GLP-1 receptor agonists may benefit osteoarthritis through both weight loss and direct anti-inflammatory effects on cartilage. The STEP-9 trial showed significant pain reduction in knee OA.","whyItMatters":"Over 500 million people have osteoarthritis with no disease-modifying drugs approved. If GLP-1 drugs can slow joint damage beyond just reducing body weight, it would be a major advance.","specificNumbers":"OA affects 500+ million people globally; STEP-9 showed significant weight loss and pain reduction with semaglutide in knee OA","methodology":"Narrative review of clinical and preclinical evidence on GLP-1 receptor agonists in osteoarthritis, covering weight-dependent and weight-independent mechanisms.","limitations":"Narrative review without systematic search. Most evidence for direct joint effects is preclinical. Pain relief may be primarily weight-dependent. Long-term cartilage outcomes unknown."},{"rthcId":"RPEP-13341","title":"Beyond Diabetes: The Vasculoprotective Effects and Anti-Atherosclerotic Potential of Tirzepatide.","authors":"Rzepiński, Łukasz; Tywoniuk, Anna; Jaraczewska, Justyna; Al-Shaer, Aysheh; Wiciński, Michał","year":2025,"journal":"International journal of molecular sciences, 26(24)","doi":"10.3390/ijms262412028","pmid":"41465455","tags":["tirzepatide","cardiovascular-outcomes","inflammation","atherosclerosis"],"studyType":"narrative review","evidenceStrength":"low (review of field)","keyFinding":"Tirzepatide shows anti-atherosclerotic effects beyond blood sugar control, including improved endothelial function, reduced inflammation, better lipid profiles, and lower blood pressure.","whyItMatters":"Heart disease is the leading killer in people with diabetes and obesity. Understanding how tirzepatide protects blood vessels could expand its use for cardiovascular prevention.","specificNumbers":"N/A (mechanistic review; cites reductions in TNF-alpha, IL-1-beta, IL-6, total cholesterol, LDL, triglycerides; increases in HDL and eNOS activity)","methodology":"Narrative review of preclinical and clinical studies on tirzepatides vascular and anti-atherosclerotic mechanisms.","limitations":"Narrative format without systematic methodology. Most mechanistic data from preclinical models. Long-term cardiovascular outcome data from dedicated trials are still emerging."},{"rthcId":"RPEP-13342","title":"Sacubitril/Valsartan Improves Hemodynamic Parameters of Pulmonary and Systemic Circulation in Patients Awaiting Heart Transplantation.","authors":"Ráduly, Arnold Péter; Saman Kothalawala, Edward; Balogh, László; Majoros, Zsuzsanna; Pólik, Zsófia; Fülöp, László; Győry, Ferenc; Nagy, László; Bódi, Beáta; Kovács, Máté Balázs; Csanádi, Zoltán; Papp, Zoltán; Muk, Balázs; Borbély, Attila","year":2025,"journal":"Journal of clinical medicine, 14(8)","doi":"10.3390/jcm14082539","pmid":"40283370","tags":["natriuretic-peptides","cardiovascular-effects","clinical-applications"],"studyType":"observational","evidenceStrength":"low-moderate","keyFinding":"Sacubitril/valsartan improved hemodynamic parameters of both pulmonary and systemic circulation compared to conventional ACE inhibitors/ARBs in patients with advanced heart failure awaiting transplantation.","whyItMatters":"Improving hemodynamics while waiting for transplant can reduce complications, improve quality of life, and potentially improve transplant candidacy and outcomes.","specificNumbers":"Retrospective analysis; improved echocardiographic and hemodynamic parameters; reduced NT-proBNP; patients awaiting HTX.","methodology":"Retrospective analysis comparing echocardiographic, laboratory, and hemodynamic parameters before and after switching to sacubitril/valsartan in advanced heart failure patients awaiting heart transplantation.","limitations":"Retrospective study design limits causal conclusions; single-center data; no randomized control group; small sample size typical for transplant-waitlist populations."},{"rthcId":"RPEP-13343","title":"A Review of the Biochemical Diagnostic Biomarkers in Migraine: New Perspectives in Diagnostics.","authors":"Różycka, Karolina; Siwak, Natalia; Rucka, Aleksandra; Bielewicz, Joanna; Rejdak, Konrad","year":2025,"journal":"Pain research & management, 2025, 9478767","doi":"10.1155/prm/9478767","pmid":"41496770","tags":["biomarkers","cgrp","neuropeptides","diagnostics"],"studyType":"systematic review","evidenceStrength":"moderate","keyFinding":"CGRP and PACAP are the most promising blood-based biomarkers for migraine diagnosis, but no single substance is ready for routine clinical use yet.","whyItMatters":"Migraine diagnosis currently relies only on symptoms. A reliable blood test could speed up diagnosis and help doctors choose the right treatment faster.","specificNumbers":"31 studies reviewed; CGRP and PACAP identified as most promising candidates; databases searched over 5-year period","methodology":"Systematic review following PRISMA guidelines. Searched MEDLINE, Web of Science, and Embase for studies on biochemical biomarkers in migraine diagnosis in adults and children.","limitations":"High variability in methods across included studies. No meta-analysis performed. No single biomarker met criteria for clinical adoption. Search limited to 5 years."},{"rthcId":"RPEP-13344","title":"Early Development of Hypothalamic Neurons Expressing Proopiomelanocortin Peptides, Neuropeptide Y, and Kisspeptin in Fetal Rhesus Macaques.","authors":"Rønnekleiv, Oline K; Bosch, Martha A","year":2025,"journal":"eNeuro, 12(7)","doi":"10.1523/ENEURO.0087-25.2025","pmid":"40389300","tags":["neuropeptides","neuropeptide-y","preclinical-research"],"studyType":"preclinical","evidenceStrength":"low","keyFinding":"In fetal rhesus macaques, appetite-regulating hypothalamic neurons (POMC and NPY) develop much earlier than previously thought, with POMC neurons appearing by day 32-34 and NPY neurons by day 44 of gestation.","whyItMatters":"Understanding when appetite-control brain circuits form in primates informs research on how maternal nutrition and exposures during pregnancy may permanently alter offspring metabolism and obesity risk.","specificNumbers":"Beta-endorphin/alpha-MSH neurons: day 32-34 of gestation (lateral basal hypothalamus), migrated to medial basal hypothalamus by day 45. NPY neurons: day 44. Kisspeptin: few cells at day 44, expanded distribution by day 70 and 130.","methodology":"Immunohistochemistry for beta-endorphin, alpha-MSH, NPY, and kisspeptin in fetal rhesus macaque brains at multiple gestational ages. Both male and female fetuses examined.","limitations":"Descriptive neuroanatomical study. Rhesus macaque brain development similar but not identical to human. No functional testing of these neurons. Small numbers of fetal specimens at each age."},{"rthcId":"RPEP-13345","title":"GLP-1 receptor agonists and preconception planning: bridging the gap between obesity treatment and reproductive safety, a narrative review.","authors":"Saad Alfaiz, Abdulrahman","year":2025,"journal":"Annals of medicine and surgery (2012), 87(12), 8597-8603","doi":"10.1097/MS9.0000000000004189","pmid":"41377305","tags":["glp1-receptor-agonists","semaglutide","tirzepatide","liraglutide","reproductive-health"],"studyType":"narrative review","evidenceStrength":"low (review of field)","keyFinding":"Semaglutide should be stopped at least 35 days before conception and tirzepatide 25-35 days before, based on their half-lives. Limited human data show no clear increase in birth defects from accidental early exposure.","whyItMatters":"Millions of women of childbearing age now use GLP-1 drugs. Clear guidance on when to stop before pregnancy is essential for safe family planning.","specificNumbers":"Semaglutide half-life ~7 days, discontinue 35+ days before conception; tirzepatide ~5 days, discontinue 25-35 days; liraglutide discontinue 3+ days; 132 articles screened, 9 included","methodology":"Narrative review with systematic search of PubMed, Scopus, Web of Science, and Google Scholar. 132 articles screened, 9 met inclusion criteria.","limitations":"Only 9 studies met criteria, most observational. No large prospective studies on pregnancy outcomes with GLP-1 RA exposure. Animal data may not apply to humans."},{"rthcId":"RPEP-13346","title":"Structure and Dynamics of the Magainin 2 Antimicrobial Peptide in Biomimetic Lipid Bilayers by Solid-State NMR.","authors":"Saad, Ahmad; Raya, Jesus; Bechinger, Burkhard","year":2025,"journal":"Biochemistry, 64(20), 4296-4308","doi":"10.1021/acs.biochem.5c00467","pmid":"41021901","tags":["antimicrobial-peptides","structure-activity-relationships","membrane-interactions"],"studyType":"laboratory study","evidenceStrength":"low (in vitro)","keyFinding":"Magainin 2 adopts different structures depending on membrane type. In bacterial-like membranes it can form amyloid-like beta-sheet aggregates, but not in mammalian-like membranes.","whyItMatters":"This may explain why antimicrobial peptides like magainin 2 kill bacteria but spare human cells. The amyloid-like structures could be a new mechanism of antimicrobial action.","specificNumbers":"N/A (structural characterization study using 13C and 15N solid-state NMR)","methodology":"Solid-state NMR spectroscopy (13C chemical shift analysis, oriented 15N NMR) of magainin 2 reconstituted in biomimetic lipid bilayers mimicking bacterial and mammalian membranes.","limitations":"In vitro membrane model study. Artificial bilayers may not fully replicate living cell membranes. Amyloid-like structures observed in lab conditions may behave differently in vivo."},{"rthcId":"RPEP-13347","title":"Repurposing liraglutide to the management of DSS-induced colitis: a potential for promoting autophagy.","authors":"Saadoun, Ahmed Atef; Abdelsattar, Alia Hamed; Elsaid, Amro Hatem; Abdelaleam, Eslam Abdelaziz; Abdelkader, Hazem Khaled; Ibrahim, Hend Mohamed; Saad, Merna Sabri; Ellawi, Moumen Said; Elsaid, Rana Elshahawi; Maghrabia, Aya; Ibrahim, Dina; Ramadan, Nehal M","year":2025,"journal":"Naunyn-Schmiedeberg's archives of pharmacology, 398(12), 17173-17185","doi":"10.1007/s00210-025-04339-w","pmid":"40471244","tags":["glp1-receptor-agonists","liraglutide","inflammation","gut-health"],"studyType":"preclinical study (animal model)","evidenceStrength":"low (animal study)","keyFinding":"Liraglutide reduced colitis symptoms in mice by enhancing autophagy and suppressing Paneth cell metaplasia in the colon.","whyItMatters":"Ulcerative colitis has limited treatment options. If GLP-1 drugs promote cellular cleanup in the gut, they could be repurposed for inflammatory bowel disease.","specificNumbers":"7-day DSS protocol (3% w/v); dose-dependent improvements in DAI, colon length, and histopathology scores; reduced lysozyme expression; enhanced autophagosome formation","methodology":"Mouse model of acute colitis using 7-day DSS administration. Liraglutide given at multiple doses. Outcomes: disease activity index, colon length, histology, lysozyme expression, electron microscopy for autophagosomes, p62 accumulation with chloroquine co-treatment.","limitations":"Mouse model of acute colitis may not reflect human chronic UC. Short 7-day protocol. No long-term safety or efficacy data. Mechanism inferred from autophagy markers, not directly proven."},{"rthcId":"RPEP-13348","title":"Botulinum neurotoxin A for treatment of pain in lower extremity ulcers: an exploratory study.","authors":"Sabah, Lubna; Burian, Ewa Anna; Ågren, Magnus S; Kirketerp-Møller, Klaus; Thomsen, Simon Francis; Moltke, Finn Borgbjerg","year":2025,"journal":"Journal of wound care, 34(8), 608-615","doi":"10.12968/jowc.2024.0285","pmid":"40960649","tags":["cgrp","neuropeptides","wound-healing","pain-management"],"studyType":"prospective open-label clinical trial","evidenceStrength":"low (exploratory, small sample)","keyFinding":"Botulinum toxin A injections around leg ulcers reduced neuropathic pain in 70% of patients by day 21, with wound area shrinking significantly from day 60 onward.","whyItMatters":"Leg ulcer pain is common and hard to treat. Botulinum toxin could offer a new approach that addresses both pain and potentially wound healing.","specificNumbers":"10 patients; 70% had 20+ mm pain reduction on VAS at day 21; 7 venous ulcers, 3 inflammatory; significant wound area reduction from day 60; CGRP and IL-1-beta tracked healing","methodology":"Prospective, open-label, single-arm trial. Perilesional BTX-A injections on day 0. Follow-up at days 21, 60, and 90. Pain assessed by VAS and DN4 questionnaire. Wound fluid analyzed for IL-1-beta and CGRP.","limitations":"Only 10 patients, no control group, open-label design. Cannot distinguish drug effect from placebo. Mixed ulcer types. Single-center study."},{"rthcId":"RPEP-13349","title":"Comparative Efficacy of Metabolic/Bariatric Surgery Versus GLP-1 Receptor Agonists: A Network Meta-Analysis of Randomized Controlled Trials.","authors":"Sabatella, Lucas; Ortega, Patricia M; Azcárate, Víctor Valentí; Sastre, Fernando Rotellar; Pagola, Adriana Uriz; Ahmed, Ahmed; Purkayastha, Sanjay; Ojanguren, Carlota Tuero; Asensio, Nuria Blanco; Landecho, Manuel F","year":2025,"journal":"Obesity (Silver Spring, Md.)","doi":"10.1002/oby.70100","pmid":"41326176","tags":["glp1-receptor-agonists","tirzepatide","obesity","weight-management"],"studyType":"network meta-analysis","evidenceStrength":"strong","keyFinding":"Bariatric surgery produced greater weight loss than GLP-1 drugs overall, but tirzepatide specifically was not significantly different from surgery in head-to-head comparisons.","whyItMatters":"This is the first network meta-analysis directly comparing surgery and the newest GLP-1 drugs. It shows tirzepatide is closing the gap with surgical outcomes.","specificNumbers":"30 RCTs; n=20,015; surgery vs GLP-1 RA: -9.1% TWL at 104+ wk (p=0.022), -14.6 kg (p=0.049); tirzepatide vs surgery: not significant; similar HbA1c improvement in T2D","methodology":"Network meta-analysis of RCTs comparing bariatric surgery or GLP-1 RAs (including tirzepatide) to lifestyle intervention. Random-effects models with lifestyle as common comparator. All surgery vs drug comparisons were indirect.","limitations":"All surgery vs GLP-1 RA comparisons are indirect (no head-to-head RCTs). Heterogeneity across surgical procedures and drug doses. Follow-up durations varied. Publication bias possible."},{"rthcId":"RPEP-13350","title":"Safety considerations of semaglutide in the potential treatment of Alzheimer's disease: A pooled analysis of semaglutide in adults aged ≥ 65 years.","authors":"Sabbagh, Marwan; Boschini, Cristina; Cohen, Sharon; Fugger, Magnus; Jessen, Frank; Dandanell, Sune; Pedersen, Sue D; Tarazona, Luis Rafael Solís; Aroda, Vanita R","year":2025,"journal":"Alzheimer's & dementia (New York, N. Y.), 11(2), e70076","doi":"10.1002/trc2.70076","pmid":"40337158","tags":["glp1-receptor-agonists","semaglutide","safety-profile","aging","neuroprotection"],"studyType":"pooled post hoc safety analysis","evidenceStrength":"moderate","keyFinding":"In adults 65 and older, semaglutide had a similar safety profile to the general population. GI side effects were the most common. Discontinuation rates were slightly higher in older adults (9-12% vs 6-9%).","whyItMatters":"Semaglutide is being tested for Alzheimers disease in older adults. This safety analysis from diabetes and obesity trials provides baseline safety data for this population.","specificNumbers":"3,529 participants aged 65+; AEs in 73.6-92.4% (vs 73.2-90.8% overall); GI AEs 44.6-73.8%; discontinuation 9.3-12.4% (vs 5.7-8.7% overall); 3.8% weight loss at 52 wk vs 0.1% placebo","methodology":"Pooled post hoc analysis of adverse event data from three semaglutide Phase 3a programs. Participants aged 65+ compared to overall population. Weight change assessed in a subset.","limitations":"Post hoc analysis, not designed to study older adults specifically. Pooled across diabetes and obesity trials with different populations. Does not include Alzheimers patients. Older adults in trials may be healthier than typical geriatric populations."},{"rthcId":"RPEP-13351","title":"Sex-Specific Effects of Sleep Restriction on Food Intake and Neuropeptide Expression in Zebrafish.","authors":"Sabella, Agustina; Canesini, Guillermina; Gaydou, Luisa; Schumacher, Rocío; Baños, Adrián Exequiel; Stoker, Cora; Sigot, Valeria; Fernández, Pamela Rocío; Ramos, Jorge Guillermo; García, Ana Paula","year":2025,"journal":"Journal of sleep research, e70235","doi":"10.1111/jsr.70235","pmid":"41200849","tags":["neuropeptides","hormone-regulation","appetite-regulation","sleep"],"studyType":"preclinical study (animal model)","evidenceStrength":"low (animal study)","keyFinding":"Sleep restriction increased food intake in male zebrafish and lowered brain POMC levels. Female zebrafish responded differently, spending less time feeding instead.","whyItMatters":"Sleep loss drives overeating in mammals. This zebrafish study confirms the link extends to fish and reveals sex differences in how sleep disruption affects appetite-regulating brain peptides.","specificNumbers":"n=30 males, n=27 females; males: significant increase in food intake (mg and pellets); reduced POMC mRNA in sleep-restricted males; females: decreased feeding time","methodology":"Controlled experiment with three groups: nighttime vibration (sleep restriction), daytime vibration (control for vibration stress), and no vibration. Individually and group-housed adult zebrafish. Food intake measured daily. Brain neuropeptide expression by RT-qPCR.","limitations":"Zebrafish brain circuits differ from mammalian systems. Sleep measured behaviorally, not by EEG. Small sample sizes. Short-term sleep restriction protocol. Cannot directly translate to human sleep and appetite."},{"rthcId":"RPEP-13352","title":"Setting higher standards for migraine prevention: A position statement of the International Headache Society.","authors":"Sacco, Simona; Ashina, Messoud; Diener, Hans-Christoph; Haghdoost, Faraidoon; Lee, Mi Ji; Monteith, Teshamae S; Jenkins, Bronwyn; Peres, Mario F P; Pozo-Rosich, Patricia; Ornello, Raffaele; Puledda, Francesca; Sakai, Fumihiko; Schwedt, Todd J; Terwindt, Gisela; Vaghi, Gloria; Wang, Shuu-Jiun; Ahmed, Fayyaz; Tassorelli, Cristina","year":2025,"journal":"Cephalalgia : an international journal of headache, 45(2), 3331024251320608","doi":"10.1177/03331024251320608","pmid":"39980456","tags":["cgrp","neuropeptides","neurological-disorders","clinical-guidelines"],"studyType":"position statement / expert consensus","evidenceStrength":"low (expert opinion)","keyFinding":"The International Headache Society proposes shifting migraine prevention goals from percentage-based improvement to absolute targets: migraine freedom or fewer than 4 moderate-severe headache days per month.","whyItMatters":"A 50% reduction in migraine days is the current standard of success, but patients may still have significant disability. Setting higher goals could push treatment innovation and improve quality of life.","specificNumbers":"Migraine freedom: 0 days; optimal control: <4 days; modest: 4-6 days; insufficient: >6 days with moderate-severe headache per month","methodology":"Expert consensus position statement from the International Headache Society, informed by clinical trial data and real-world studies on CGRP inhibitors and onabotulinumtoxinA.","limitations":"Expert opinion, not based on new original data. Proposed tiers need validation in clinical practice. May not apply equally to all patient populations or healthcare settings."},{"rthcId":"RPEP-13353","title":"Bladder Trigone as a Sensory Hub: A Narrative Review.","authors":"Sadahira, Takuya; Maruyama, Yuki; Mitsui, Yosuke; Sekito, Takanori; Watanabe, Tomofumi; Watanabe, Masami","year":2025,"journal":"Cureus, 17(10), e94951","doi":"10.7759/cureus.94951","pmid":"41267700","tags":["cgrp","neuropeptides","pain-management","urological"],"studyType":"narrative review","evidenceStrength":"low (review of field)","keyFinding":"The bladder trigone contains three distinct classes of sensory nerve fibers using CGRP, substance P, and TRPV1 signaling. Dysfunction in these fibers drives urgency, frequency, and bladder pain.","whyItMatters":"Understanding the trigone as a sensory hub could lead to targeted treatments for overactive bladder and interstitial cystitis that work better than current whole-bladder approaches.","specificNumbers":"3 afferent fiber classes identified; key markers: P2X3, TRPV1, CGRP, substance P, PIEZO1/2, ASICs, Nav1.8","methodology":"Narrative review synthesizing anatomical mapping, receptor profiling, electrophysiology, and translational research on bladder trigone sensory signaling.","limitations":"Narrative review without systematic methodology. Most mechanistic data from animal models. Clinical trial data on trigone-targeted therapies are early-stage."},{"rthcId":"RPEP-13354","title":"Scalable recombinant production of bioactive human neutrophil peptide-1 in Komagataella phaffii.","authors":"Sadeeq, Mohd; Wang, Chaozhi; Yu, Ke; Cui, Shibin; Bian, Linxuan; Hou, Feifei; Zuo, Jia; Xiong, Peng","year":2025,"journal":"AMB Express, 15(1), 175","doi":"10.1186/s13568-025-01985-4","pmid":"41350511","tags":["antimicrobial-peptides","peptide-drug-design","antimicrobial-resistance"],"studyType":"laboratory study (biotechnology)","evidenceStrength":"low (in vitro)","keyFinding":"A yeast-based system produced 15.25 mg/L of pure human neutrophil peptide-1, the highest reported recombinant yield. The peptide killed both S. aureus and E. coli without harming red blood cells.","whyItMatters":"Antimicrobial peptides are promising against drug-resistant bacteria, but producing enough of them has been a major bottleneck. This system could make clinical development feasible.","specificNumbers":"15.25 mg/L pure HNP-1; 122 mg/L fusion protein in 5L bioreactor; 19.75 mg/L in shake flasks; active against S. aureus and E. coli; pH 6.0 optimal; 96h induction","methodology":"Recombinant expression in K. phaffii using codon-optimized HNP-1 fused to His6-SUMO tag with alpha-factor secretion signal. Shake flask optimization followed by 5L bioreactor scale-up. Purification, tag cleavage, antimicrobial and hemolysis assays.","limitations":"In vitro antimicrobial activity only. No animal efficacy data. Production yield, while highest reported, may still need improvement for commercial scale. Single yeast strain tested."},{"rthcId":"RPEP-13355","title":"Designing influenza virus-derived cell-penetrating peptides for antigen delivery: Integrating uptake efficiency, safety, and receptor targeting.","authors":"Sadeh, Sanaz; Ghaemi, Amir; Soleimani, Nazila Arbab; Moghbeli, Majid; BahramAli, Golnaz","year":2025,"journal":"PloS one, 20(12), e0338028","doi":"10.1371/journal.pone.0338028","pmid":"41364690","tags":["peptide-drug-design","drug-delivery-systems","vaccine-development","cell-penetrating-peptides"],"studyType":"computational study","evidenceStrength":"low (in silico only)","keyFinding":"A peptide from influenza PB1 protein (PB1-1: RGDTQIQTRR) showed high predicted cell penetration and strong binding to lung sialic acid receptors, suggesting potential for targeted vaccine delivery.","whyItMatters":"Getting vaccines and antigens into cells efficiently is a major challenge. Virus-derived cell-penetrating peptides could exploit natural viral entry routes for targeted drug delivery.","specificNumbers":"PB1-1 sequence: RGDTQIQTRR; screened using CellPPD, C2Pred, PreTP-EL; binding to LSTc confirmed by molecular docking and dynamics; low predicted toxicity","methodology":"Computational screening of influenza proteome for cell-penetrating peptides using CellPPD, C2Pred, and PreTP-EL. Safety assessed via ToxinPred and AllerTop. Structure predicted by AlphaFold. Binding to LSTc by molecular docking and dynamics simulations.","limitations":"Entirely computational; no experimental validation. Predicted properties may not translate to actual cell penetration or safety. Influenza-derived sequences could raise immunogenicity concerns."},{"rthcId":"RPEP-13356","title":"Cardiovascular benefits of semaglutide: a systematic review and meta-analysis of randomized controlled trials.","authors":"Sadraei, Samin; Aarabi, Aryan; Rajai Firouzabadi, Shahryar; Alinejadfard, Mohammadreza; Mohammadi, Ida; Jolfayi, Amir Ghaffari","year":2025,"journal":"BMC cardiovascular disorders, 25(1), 881","doi":"10.1186/s12872-025-05278-3","pmid":"41272444","tags":["glp1-receptor-agonists","semaglutide","cardiovascular-outcomes","meta-analysis"],"studyType":"systematic review and meta-analysis","evidenceStrength":"strong","keyFinding":"Semaglutide reduced major adverse cardiovascular events by 19% across four RCTs with 27,617 participants. It also lowered cardiovascular death and nonfatal heart attack risk but not stroke or heart failure hospitalization.","whyItMatters":"This is the first meta-analysis pooling all semaglutide cardiovascular RCTs, confirming a consistent heart benefit while flagging that treatment discontinuation rates are higher than placebo.","specificNumbers":"4 RCTs; n=27,617; MACE RR 0.81 (95% CI 0.74-0.88); serious AEs RR 0.91 (95% CI 0.88-0.94); discontinuation RR 1.67 (95% CI 1.27-2.21); I-squared 0% for MACE","methodology":"Systematic review per PROSPERO protocol. PubMed, Scopus, Web of Science searched. Random-effects meta-analysis of RCTs. Quality assessed with Cochrane RoB 2.","limitations":"Only four trials included. High heterogeneity for discontinuation outcome (I-squared 91%). Cannot separate effects by dose or formulation. Publication bias possible with limited trial count."},{"rthcId":"RPEP-13357","title":"Comparison of Semaglutide or Dulaglutide Versus Empagliflozin for Risk for Death and Cardiovascular Outcomes Among Patients With Type 2 Diabetes : Two Target Trial Emulation Studies.","authors":"Saeed, Anum; Mulukutla, Suresh R; Thoma, Floyd; Lemon, Lara; Koczo, Agnes; Reis, Steven; Marroquin, Oscar; Kip, Kevin","year":2025,"journal":"Annals of internal medicine, 178(7), 930-939","doi":"10.7326/ANNALS-24-00775","pmid":"40523289","tags":["glp1-receptor-agonists","semaglutide","cardiovascular-outcomes","type-2-diabetes","sglt2-inhibitors"],"studyType":"target trial emulation (observational)","evidenceStrength":"moderate","keyFinding":"Semaglutide showed a nonsignificant trend toward lower death, MI, or stroke compared to empagliflozin (HR 0.89), with a significant 38% lower stroke risk. Dulaglutide showed no advantage over empagliflozin.","whyItMatters":"No head-to-head RCTs compare GLP-1 drugs to SGLT-2 inhibitors. This large observational study provides the first direct comparison between semaglutide and empagliflozin for cardiovascular outcomes.","specificNumbers":"7,899 per group; median 2.2 yr follow-up; composite HR 0.89 (95% CI 0.78-1.02); stroke HR 0.62 (95% CI 0.43-0.89); dulaglutide composite HR 1.03 (95% CI 0.90-1.16)","methodology":"Target trial emulation using observational data from 703 US practices. Propensity score matching. Cox proportional hazards models for composite and individual outcomes.","limitations":"Observational design with possible residual confounding. No data on cause-specific mortality. Cannot account for all differences in patient selection. Not a randomized comparison."},{"rthcId":"RPEP-13358","title":"Periorbital Changes Following Glucagon-Like Peptide-1 Receptor Agonist Use: A Retrospective Cohort Study of Oculofacial Complications and Interventions.","authors":"Saffari, Persiana S; Davila, Natalia; Pradeep, Tejus; Wong, Brian; Lee, Wendy W","year":2025,"journal":"Ophthalmic plastic and reconstructive surgery","doi":"10.1097/IOP.0000000000003129","pmid":"41251628","tags":["glp1-receptor-agonists","obesity","safety-profile","cosmetic-effects"],"studyType":"retrospective cohort study","evidenceStrength":"moderate","keyFinding":"GLP-1 receptor agonist users with obesity were more likely to develop drooping eyelids, excess eyelid skin, and brow sagging, and more likely to need corrective surgery compared to non-users.","whyItMatters":"Rapid facial fat loss from GLP-1 drugs can cause visible aging around the eyes. This is the first large study quantifying these periorbital changes and resulting surgical interventions.","specificNumbers":"Significant increases in brow ptosis (p<0.001-0.004), dermatochalasis (p<0.001), blepharoptosis repair (p<0.001), blepharoplasty (p<0.001), rhytidectomy (p=0.011) in obesity GLP-1 users vs controls","methodology":"Retrospective cohort using TriNetX database. Separate analyses for T2DM and obesity groups. GLP-1 users compared to matched GLP-1-naive controls. Outcomes assessed at 3 years (obesity) and 20 years (T2DM).","limitations":"Retrospective database study relying on diagnostic codes. Cannot confirm changes are directly caused by GLP-1 drugs versus weight loss itself. Different follow-up periods for obesity and diabetes groups. No dose-response analysis."},{"rthcId":"RPEP-13359","title":"Screening of Angiotensin-I Converting Enzyme (ACE) Inhibitory Peptides from Thermolytic Hydrolysate of Arthrospira platensis.","authors":"Safitri, Nur Maulida; Hsu, Jue-Liang","year":2025,"journal":"Marine biotechnology (New York, N.Y.), 27(2), 61","doi":"10.1007/s10126-025-10437-w","pmid":"40067533","tags":["bioactive-peptides","blood-pressure","peptide-drug-design","food-derived-peptides"],"studyType":"laboratory study","evidenceStrength":"low (in vitro)","keyFinding":"Two peptides from spirulina (Arthrospira platensis) inhibited the blood pressure enzyme ACE. The peptide IR5 (ILLYR) was a non-competitive inhibitor with an IC50 of 10.54 micromolar.","whyItMatters":"Finding natural ACE inhibitors from food sources like spirulina could lead to dietary supplements or functional foods that help manage blood pressure.","specificNumbers":"IR5 (ILLYR) IC50: 10.54 +/- 1.38 microM; FY11 (FSESSAPEQHY) m/z 1281.54; IR5 m/z 677.37; docking energy -106.842 kJ/mol; 2.42 microg/mg crude digest","methodology":"Thermolysin digestion of A. platensis protein. Peptide isolation by RP-HPLC and SCX chromatography. Sequencing by LC-MS/MS. ACE inhibition assay. Molecular docking for binding mode.","limitations":"In vitro ACE inhibition only. No cell or animal studies. Bioavailability and stability of the peptide in the digestive tract are unknown. Docking is a computational prediction."},{"rthcId":"RPEP-13360","title":"Gastrointestinal safety of semaglutide and tirzepatide vs. placebo in obese individuals without diabetes: a systematic review and meta analysis.","authors":"Safwan, Moaz; Bourgleh, Mariam Safwan; Alotaibi, Shahad Abdullah; Alotaibi, Eman; Al-Ruqi, Abdulsalam; El Raeya, Fathiya","year":2025,"journal":"Annals of Saudi medicine, 45(2), 129-143","doi":"10.5144/0256-4947.2025.129","pmid":"40189856","tags":["glp1-receptor-agonists","semaglutide","tirzepatide","gastrointestinal-effects","safety-profile"],"studyType":"systematic review and meta-analysis","evidenceStrength":"strong","keyFinding":"Both semaglutide and tirzepatide nearly doubled GI side effects versus placebo. Tirzepatide had higher GI risk (RR 2.94) than semaglutide (RR 1.68). Semaglutide increased gallstone risk 2.6-fold but tirzepatide did not.","whyItMatters":"With millions using these drugs for weight loss, understanding the distinct GI safety profiles helps clinicians choose the right drug and monitor for specific complications.","specificNumbers":"13 RCTs; n=26,894; overall GI RR 1.86 (95% CI 1.56-2.21); tirzepatide GI RR 2.94 (95% CI 2.61-3.32); semaglutide GI RR 1.68 (95% CI 1.46-1.94); semaglutide cholelithiasis RR 2.6 (95% CI 1.40-4.82)","methodology":"Systematic review and meta-analysis of RCTs comparing semaglutide or tirzepatide to placebo in obese adults without diabetes. Pooled risk ratios for GI, biliary, hepatic, and pancreatic adverse events.","limitations":"Trials had different follow-up durations and doses. Cannot compare semaglutide and tirzepatide directly since they were compared to placebo separately. Limited data on rare events like pancreatic cancer."},{"rthcId":"RPEP-13361","title":"Navigating cancer therapy: Harnessing the power of peptide-drug conjugates as precision delivery vehicles.","authors":"Sagar, Bulbul; Gupta, Sarthak; Verma, Sarvesh Kumar; Reddy, Y Veera Manohara; Shukla, Shefali","year":2025,"journal":"European journal of medicinal chemistry, 283, 117131","doi":"10.1016/j.ejmech.2024.117131","pmid":"39647418","tags":["peptide-drug-design","cancer-immunotherapy","drug-delivery-systems","cell-penetrating-peptides"],"studyType":"narrative review","evidenceStrength":"low (review of field)","keyFinding":"Peptide-drug conjugates offer targeted cancer delivery by linking tumor-homing peptides to cytotoxic drugs via specialized linkers, reducing off-target toxicity compared to chemotherapy.","whyItMatters":"Traditional chemotherapy damages healthy cells alongside cancer cells. PDCs aim to deliver the drug directly to tumors, potentially improving outcomes while reducing side effects.","specificNumbers":"PDC components: targeting ligand + cytotoxic payload + linker; several in clinical trials; challenges: plasma stability, elimination, oral bioavailability","methodology":"Narrative review of PDC design, delivery mechanisms, clinical applications, and limitations.","limitations":"Narrative format without systematic search. Many PDCs discussed are still experimental. Clinical data are limited for most candidates."},{"rthcId":"RPEP-13362","title":"A Bivalent Protease-Activated Receptor-Derived Peptide Mimics Neuronal Anti-Apoptotic Activity of Activated Protein C.","authors":"Sagare, Abhay; Kim, Youbin; Kisler, Kassandra; Rust, Ruslan; Mack, William J; Fernández, José A; Zlokovic, Berislav V; Griffin, John H","year":2025,"journal":"Bioengineering (Basel, Switzerland), 12(9)","doi":"10.3390/bioengineering12090899","pmid":"41007144","tags":["neuroprotection","peptide-drug-design","coagulation-peptides","cell-signaling"],"studyType":"preclinical study (in vitro)","evidenceStrength":"low (cell culture)","keyFinding":"A synthetic 34-amino-acid peptide (G10) that combines PAR1 and PAR3 sequences mimicked all three cytoprotective activities of activated protein C, including anti-apoptotic effects in neurons.","whyItMatters":"Activated protein C protects cells but is hard to use as a drug. A short peptide that copies its protective effects could be developed into a practical treatment for stroke and other conditions.","specificNumbers":"34-residue G10 peptide; PAR1 residues 47-55 linked by 10 glycines to PAR3 residues 51-65; anti-apoptotic in NMDA-challenged murine neurons; mimics all 3 APC cytoprotective activities","methodology":"In vitro study using cultured murine neurons challenged with NMDA to induce apoptosis. G10 peptide compared to APC for anti-apoptotic activity.","limitations":"Cell culture only; no animal studies in this paper. Neurons were from mice, not humans. NMDA challenge is one model of injury and may not represent all clinical scenarios."},{"rthcId":"RPEP-13363","title":"Histone Arginine Methylation Regulates Neuropeptide Y Expression in the Basolateral Amygdala to Promote Reward-Seeking Behaviour.","authors":"Sagarkar, Sneha; Rotti, Deepa; Raykar, Sahil; Upadhye, Gauri A; Sakharkar, Amul J","year":2025,"journal":"Cellular and molecular neurobiology, 45(1), 92","doi":"10.1007/s10571-025-01614-5","pmid":"41134392","tags":["neuropeptides","neuropeptide-y","epigenetics","brain-function"],"studyType":"preclinical study (animal model)","evidenceStrength":"low (animal study)","keyFinding":"Histone arginine methylation by PRMT4 in the basolateral amygdala controls neuropeptide Y expression and is required for reward-seeking behavior in rats.","whyItMatters":"Understanding how brain chemistry drives reward-seeking could inform treatments for overeating and addiction, where neuropeptide Y plays a key role.","specificNumbers":"Increased PRMT4 and NPY in BLA after operant conditioning; H3R17me2a enrichment at NPY promoter; PRMT4 siRNA/inhibitor reduced nose-poke activity; NPY peptide restored activity","methodology":"Rat operant conditioning for sucrose pellets. PRMT4 and NPY measured by immunohistochemistry. Chromatin immunoprecipitation for histone marks at NPY promoter. Intra-BLA injection of PRMT4 siRNA, inhibitor, and NPY peptide.","limitations":"Rat model; brain reward circuits differ from humans. Sucrose reward may not generalize to other reward types. Invasive brain injections are not clinically translatable. Small group sizes typical of behavioral neuroscience."},{"rthcId":"RPEP-13364","title":"GLP1 and GIP Receptor Agonists: Effects on the Gastrointestinal Tract and Management Strategies for Primary Care Physicians.","authors":"Saha, Bibek; Kamalumpundi, Vijayvardhan; Codipilly, Don C","year":2025,"journal":"Mayo Clinic proceedings","doi":"10.1016/j.mayocp.2025.09.017","pmid":"41324524","tags":["glp1-receptor-agonists","gastrointestinal-effects","safety-profile","clinical-guidelines"],"studyType":"clinical review / practice guideline","evidenceStrength":"moderate (evidence-based review)","keyFinding":"40-70% of GLP-1 drug users experience GI side effects. Dietary changes should be first-line management. For endoscopy, GLP-1 drugs can usually be continued but a 24-hour liquid diet may help high-risk patients.","whyItMatters":"Primary care doctors prescribe most GLP-1 drugs but may lack specific guidance on managing GI side effects and navigating endoscopy preparation.","specificNumbers":"40-70% GI adverse effect rate; long-acting formulations increase retained gastric contents risk; no confirmed increased aspiration risk; 24-hour liquid diet recommended for high-risk patients","methodology":"Evidence-based clinical review from Mayo Clinic Proceedings covering GI effects, management strategies, and perioperative considerations for incretin-based therapies.","limitations":"Review format; not a systematic review or meta-analysis. Perioperative guidance based on limited direct evidence. Recommendations may need updating as more data emerge."},{"rthcId":"RPEP-13365","title":"Machine learning enhanced expert system for detecting heart failure decompensation using patient reported vitals and electronic health records.","authors":"Saha, Shumit; Ross, Heather; Velmovitsky, Pedro Elkind; Wang, Chloe X; Vishram-Nielsen, Julie K K; Manlhiot, Cedric; Wang, Bo; Cafazzo, Joseph A","year":2025,"journal":"Scientific reports, 15(1), 30979","doi":"10.1038/s41598-025-16376-9","pmid":"40846740","tags":["biomarkers","cardiovascular-outcomes","digital-health","artificial-intelligence"],"studyType":"retrospective machine learning study","evidenceStrength":"moderate","keyFinding":"Adding electronic health records (especially BNP and cholesterol) to a machine learning model improved heart failure decompensation detection from 55.8% to 88.2% positive predictive value.","whyItMatters":"Heart failure patients need early warning of worsening symptoms. This AI system dramatically reduces false alarms while catching more true episodes of decline.","specificNumbers":"98.08% accuracy; 95.26% sensitivity; 98.86% specificity; 88.18% PPV (vs 55.8% in rule-based); BNP and total cholesterol were top EHR predictors","methodology":"Retrospective study using XGBoost for binary classification. Features: blood pressure, weight change, heart rate, plus EHR data (BNP, cholesterol, medications). Interpretability analysis to identify key EHR features.","limitations":"Retrospective design; needs prospective validation. Single-center data from one digital health program. Model performance may not generalize to other populations or monitoring systems."},{"rthcId":"RPEP-13366","title":"The role of the gut microbiota and the nicotinate/nicotinamide pathway in rotenone-induced neurotoxicity.","authors":"Sai, Yan; Ge, Wei; Zhong, Li; Zhang, Qifu; Xiao, Jingsong; Shan, Yaohui; Ye, Wenqi; Liu, Haoyin; Liu, Shulin; Ye, Feng; Wang, Xiaogang; Tang, He; Zhao, Yuanpeng; Dan, Guorong","year":2025,"journal":"Current research in toxicology, 8, 100212","doi":"10.1016/j.crtox.2024.100212","pmid":"39834518","tags":["gut-microbiome","neuropeptides","neurological-disorders","inflammation"],"studyType":"preclinical study (animal model)","evidenceStrength":"low (animal study)","keyFinding":"Rotenone exposure changed gut bacteria, reduced short-chain fatty acids, and disrupted the nicotinate/nicotinamide pathway in rats, with increased VIP and TNF-alpha and decreased gut barrier proteins.","whyItMatters":"Rotenone is linked to Parkinsons disease. This study suggests the gut-brain connection through microbiota disruption and NAD+ depletion may be part of the mechanism.","specificNumbers":"Significant decreases in acetic acid, butyric acid, NAD+, NAMPT, SLC25A51; significant increases in IL-6, TNF-alpha, VIP; significant decreases in gastrin, ghrelin; reduced tight junction proteins","methodology":"Rat model of rotenone exposure. Gut microbiota analysis, metabolomics, inflammatory cytokine measurement, intestinal peptide levels, tight junction protein expression, and NAD+ pathway enzyme analysis.","limitations":"Rat model; human gut microbiome differs. Rotenone exposure protocol may not match real-world pesticide exposure. Correlational findings; causal pathways not fully established."},{"rthcId":"RPEP-13367","title":"Cellular and humoral immune responses to SARS-CoV2, comparing previously infected individuals who received one vaccine dose to uninfected individuals after three vaccine doses: A case-control study.","authors":"Saiag, Esther; Shalit, Roy; Alcalay, Yifat; Hasday, Ilanit; Yakubov, Sigalit; Freund, Natalia T; Hagin, David","year":2025,"journal":"Vaccine, 62, 127525","doi":"10.1016/j.vaccine.2025.127525","pmid":"40706511","tags":["immune-modulation","vaccine-development","infectious-disease"],"studyType":"case-control immunology study","evidenceStrength":"moderate","keyFinding":"People who recovered from COVID-19 and received one vaccine dose had comparable antibody responses and stronger T-cell responses (especially to membrane protein) than uninfected people who received three vaccine doses.","whyItMatters":"Understanding how natural immunity plus vaccination compares to vaccination alone helps optimize vaccine strategies and reduce unnecessary doses.","specificNumbers":"Convalescent+1 dose vs naive+3 doses: IFN-gamma to WT Spike: 988 vs 590 per 10^6 CD4+ (p=0.022); to M protein: 2291 vs 239 (p=0.023); comparable RBD binding and ACE2 inhibition","methodology":"Case-control study comparing humoral (RBD binding, ACE2 inhibition across variants) and cellular (flow cytometry for IFN-gamma after peptide stimulation) immune responses between the two groups.","limitations":"Small sample sizes not specified in abstract. Cross-sectional comparison; does not track immunity over time. Convalescent group had both natural and vaccine immunity, confounding comparisons."},{"rthcId":"RPEP-13368","title":"Side-by-Side Comparison of the In Vivo Performance of [212Pb]Pb-DOTAMTATE and Other SSTR2-Targeting Compounds.","authors":"Saidi, Amal; Stallons, Tania A; Wong, Amy G; Schatzmann, Aaron T; Soysal, Ugur; Torgue, Julien J","year":2025,"journal":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 66(3), 391-397","doi":"10.2967/jnumed.124.268345","pmid":"39884771","tags":["peptide-drug-design","cancer-immunotherapy","radionuclide-therapy","somatostatin-analogs"],"studyType":"preclinical comparative study","evidenceStrength":"low (animal study)","keyFinding":"[212Pb]Pb-DOTAMTATE showed superior tumor-to-kidney uptake ratio compared to other somatostatin receptor-targeting peptides, making it the most promising candidate for targeted alpha therapy of neuroendocrine tumors.","whyItMatters":"Kidney damage limits how much radioactive peptide therapy can be given. A peptide that concentrates more in tumors and less in kidneys could allow higher, more effective doses.","specificNumbers":"Superior tumor-to-kidney AUC ratio for DOTAMTATE; DOTAM chelator had best chelation efficiency and fastest kinetics; compared DOTAMTATE, DOTATATE, JR11, and PSC-PEG2-TOC","methodology":"Head-to-head preclinical comparison of four SSTR2-targeting peptides labeled with 212Pb. Chelation efficiency, pharmacokinetics, and biodistribution studied in AR42J tumor-bearing animals.","limitations":"Animal model only. AR42J xenograft may not represent all human neuroendocrine tumors. 212Pb-specific dosimetry may differ from other radionuclides used clinically (e.g., 177Lu)."},{"rthcId":"RPEP-13369","title":"Androgen receptors expressed in the primary sensory neurons regulate mechanical pain sensitivity.","authors":"Saika, Fumihiro; Uta, Daisuke; Fukazawa, Yohji; Hino, Yuko; Hatano, Yu; Kishioka, Shiroh; Nawa, Hiroyuki; Hino, Shinjiro; Suzuki, Kentaro; Kiguchi, Norikazu","year":2025,"journal":"Pain, 166(12), e746-e757","doi":"10.1097/j.pain.0000000000003736","pmid":"40668025","tags":["cgrp","neuropeptides","pain-management","sex-differences","hormone-regulation"],"studyType":"preclinical study (animal model)","evidenceStrength":"low (animal study)","keyFinding":"Androgen receptors in CGRP-expressing sensory neurons regulate mechanical pain sensitivity. Removing these receptors lowered pain thresholds in male mice, while giving testosterone to females raised them.","whyItMatters":"Women report more pain conditions than men. This study identifies a specific molecular mechanism: androgens acting on CGRP neurons in sensory ganglia may explain sex differences in pain.","specificNumbers":"Male AR-cKO mice had significantly lower mechanical pain thresholds; greatest AR depletion in CGRP+ neurons; testosterone or DHT raised female thresholds; effect abolished in female AR-cKO mice","methodology":"Mouse study using castrated males, sensory neuron-selective AR conditional knockout mice, and testosterone/DHT administration in females. Pain thresholds by mechanical testing. AR expression by immunohistochemistry. Spinal cord electrophysiology.","limitations":"Mouse pain models may not fully translate to human pain conditions. Mechanical pain is one pain modality; other types not tested. Conditional knockout may not be complete in all neurons."},{"rthcId":"RPEP-13370","title":"Computational Insights Into Antimicrobial Peptide-Enhanced Dental Resin Composites: Targeting Porphyromonas gingivalis Heme-Binding Proteins and Biofilms.","authors":"Saini, Ravinder S; Dermawan, Doni; Alshadidi, Abdulkhaliq Ali F; Binduhayyim, Rayan Ibrahim H; Vyas, Rajesh; Alhamoudi, Fahad Hussain; Vaddamanu, Sunil Kumar; Kuruniyan, Mohamed Saheer; Aldosari, Lujain Ibrahim N; Heboyan, Artak","year":2025,"journal":"MicrobiologyOpen, 14(6), e70184","doi":"10.1002/mbo3.70184","pmid":"41327619","tags":["antimicrobial-peptides","peptide-drug-design","dental-applications"],"studyType":"computational study","evidenceStrength":"low (in silico only)","keyFinding":"Pardaxin showed the strongest binding to P. gingivalis heme-binding proteins among three antimicrobial peptides tested computationally, suggesting potential for antibacterial dental resin composites.","whyItMatters":"Dental fillings can harbor bacteria that cause gum disease. Adding antimicrobial peptides to resin composites could provide built-in protection at the restoration-tooth interface.","specificNumbers":"Pardaxin binding energy: -65.58 kcal/mol; Tachystatin: -48.71 kcal/mol; Thermolysin: -39.92 kcal/mol; 100 ns molecular dynamics simulations","methodology":"Computational screening: molecular docking of AMPs with resin monomers and P. gingivalis heme-binding proteins. 100 ns molecular dynamics simulations. MM/PBSA binding energy calculations.","limitations":"Entirely computational; no lab testing. Resin monomer models are static and may not represent clinical conditions. Peptide stability, release kinetics, and biocompatibility not assessed."},{"rthcId":"RPEP-13371","title":"Decoding the Role of Antimicrobial Peptides in the Fight against Mycobacterium tuberculosis.","authors":"Saini, Sapna; Pal, Sunny; Sharma, Rashmi","year":2025,"journal":"ACS infectious diseases, 11(2), 350-365","doi":"10.1021/acsinfecdis.4c00806","pmid":"39873328","tags":["antimicrobial-peptides","infectious-disease","antimicrobial-resistance"],"studyType":"narrative review","evidenceStrength":"low (review of field)","keyFinding":"Antimicrobial peptides offer broad-spectrum activity against M. tuberculosis and may bypass existing drug resistance mechanisms, but challenges in stability, delivery, and toxicity limit clinical use.","whyItMatters":"Drug-resistant tuberculosis kills hundreds of thousands yearly. AMPs work differently from conventional antibiotics and could overcome resistance that makes current drugs ineffective.","specificNumbers":"MDR-TB and XDR-TB strains increasingly common; standard TB treatment 6+ months; AMPs from diverse biological sources","methodology":"Narrative review covering AMP sources, classification, mechanisms, host induction, anti-TB efficacy, clinical status, and development challenges.","limitations":"Narrative format without systematic methodology. Most AMP efficacy data are from in vitro or animal studies. Clinical translation is still early-stage for TB applications."},{"rthcId":"RPEP-13372","title":"Regulation of glucose metabolism by incretins: implications for treatment of type 2 diabetes.","authors":"Saito, Rie; Harada, Norio","year":2025,"journal":"Diabetology international, 16(3), 442-446","doi":"10.1007/s13340-024-00781-y","pmid":"40607157","tags":["glp1-receptor-agonists","gip","type-2-diabetes","insulin-signaling","hormone-regulation"],"studyType":"mini-review","evidenceStrength":"low (review of field)","keyFinding":"The incretin effect (gut hormone-enhanced insulin release) is reduced in type 2 diabetes. GIP and GLP-1 are the two major incretins, and new combination drugs targeting both are in development.","whyItMatters":"Understanding how gut hormones control blood sugar explains why incretin-based drugs work and why combining GIP and GLP-1 targeting may be more effective than either alone.","specificNumbers":"GIP and GLP-1 are the two major incretins; incretin effect reduced in T2D; multiple mechanisms proposed","methodology":"Mini-review of incretin physiology, the incretin effect, mechanisms of its reduction in diabetes, and incretin-based drug development.","limitations":"Brief review without systematic search. Limited depth on individual drug mechanisms or clinical trial results."},{"rthcId":"RPEP-13373","title":"Fontan-Associated Liver Disease: Predictors of Elevated Liver Stiffness and the Role of Transient Elastography in Long-Term Follow-Up.","authors":"Sakae, Haruka; Tanoue, Shiroh; Mawatari, Seiichi; Oda, Kohei; Taniyama, Ohki; Toyodome, Ai; Ijuin, Sho; Tabu, Kazuaki; Kumagai, Kotaro; Ido, Akio","year":2025,"journal":"Cureus, 17(6), e85336","doi":"10.7759/cureus.85336","pmid":"40621359","tags":["biomarkers","cardiovascular-outcomes","liver-disease"],"studyType":"retrospective single-center study","evidenceStrength":"low","keyFinding":"In adults after Fontan heart surgery, the FIB-4 fibrosis index, GGT, and age at surgery were independently associated with higher liver stiffness measured by elastography.","whyItMatters":"Liver disease is a major long-term complication after Fontan surgery. Identifying which patients develop worse liver damage helps target monitoring and intervention.","specificNumbers":"37 patients; median age 27 yrs; median Fontan duration 23 yrs; median LSM 13.6 kPa (range 6.5-38.8); FIB-4 (B=6.246, p=0.008), GGT (B=0.043, p=0.034), age at Fontan (B=1.141, p=0.021) independent predictors","methodology":"Single-center retrospective study. Transient elastography (Fibroscan) during routine follow-up. Univariate and multivariate linear regression for predictors of liver stiffness.","limitations":"Small single-center study (n=37). No validated LSM cut-offs for Fontan liver disease. Cross-sectional design cannot track progression. Selection bias from routine clinic attendees."},{"rthcId":"RPEP-13374","title":"Spectroelectrochemical analysis of membrane permeation mechanisms of cell-penetrating peptide-modified fluorescent proteins.","authors":"Sakae, Hiroki; Takada, Kaho; Maruyama, Chitose; Hamano, Yoshimitsu; Nagatani, Hirohisa","year":2025,"journal":"Bioelectrochemistry (Amsterdam, Netherlands), 166, 109054","doi":"10.1016/j.bioelechem.2025.109054","pmid":"40716413","tags":["cell-penetrating-peptides","drug-delivery-systems","membrane-interactions"],"studyType":"laboratory study","evidenceStrength":"low (in vitro)","keyFinding":"Epsilon-poly-L-lysine (ePL) enabled a fluorescent protein to cross an artificial membrane, while octa-arginine (R8) disrupted the membrane structure instead. Each cell-penetrating peptide uses a different mechanism.","whyItMatters":"Understanding how different cell-penetrating peptides move cargo across membranes helps design better drug delivery systems that match the cargo to the right peptide.","specificNumbers":"Two CPPs compared: epsilon-poly-L-lysine (ePL) and octa-arginine (R8); mAG fluorescent protein cargo; water/1,2-dichloroethane interface; phospholipid-modified biomimetic interface","methodology":"Spectroelectrochemical analysis at liquid/liquid interfaces. Cyclic voltammetry and UV-Vis spectroscopy measured adsorption and transfer of CPP-modified proteins at water/DCE and phospholipid-modified interfaces.","limitations":"Artificial interface model, not living cells. Fluorescent protein cargo may behave differently than therapeutic proteins. Results may not translate directly to cellular uptake."},{"rthcId":"RPEP-13375","title":"The Potential Link Between Abdominal Migraine and Chronic Apical Periodontitis: A Case Report.","authors":"Sakai, Fuu; Ozasa, Kana; Shimizu, Kohei; Noma, Noboru","year":2025,"journal":"Cureus, 17(1), e78270","doi":"10.7759/cureus.78270","pmid":"40026941","tags":["cgrp","neuropeptides","pain-management","inflammation"],"studyType":"case report","evidenceStrength":"very low","keyFinding":"A 44-year-old woman with abdominal migraine saw symptom improvement after root canal therapy and periodontal treatment, suggesting chronic dental infection may trigger migraines via CGRP-mediated pathways.","whyItMatters":"If chronic dental infections can trigger migraines through systemic inflammation and CGRP release, treating the dental problem could help some migraine patients.","specificNumbers":"1 patient; 44-year-old female; chronic apical periodontitis; abdominal migraine per ICHD-3 criteria; improvement after root canal and periodontal treatment","methodology":"Single case report with clinical description of dental treatment and migraine outcome.","limitations":"Single case; cannot establish causation. Migraine improvement could be coincidental. No control comparison. Abdominal migraine in adults is rare and may be misdiagnosed."},{"rthcId":"RPEP-13376","title":"Ghrelin-LEAP2 interactions along the stomach-liver axis.","authors":"Sakai, Katsuya; Nakazato, Yuki; Shiimura, Yuki; Zhang, Weidong; Nakazato, Masamitsu","year":2025,"journal":"Endocrine journal, 72(4), 341-353","doi":"10.1507/endocrj.EJ24-0543","pmid":"39756956","tags":["ghrelin","appetite-regulation","hormone-regulation","obesity"],"studyType":"narrative review","evidenceStrength":"low (review of field)","keyFinding":"LEAP2, a liver-produced peptide, blocks the ghrelin receptor and opposes ghrelins hunger-promoting effects. LEAP2 levels rise with obesity while ghrelin levels fall.","whyItMatters":"The ghrelin-LEAP2 balance may be a key regulator of appetite and body weight. Understanding it could lead to new approaches for treating obesity and cachexia.","specificNumbers":"LEAP2 positively correlated with BMI, body fat, fasting glucose, and triglycerides; anamorelin launched in Japan for cancer cachexia","methodology":"Narrative review of ghrelin and LEAP2 physiology, receptor structures, and their opposing roles in metabolism.","limitations":"Narrative review without systematic search. Most LEAP2 data are from animal models. Clinical applications of LEAP2 modulation are theoretical."},{"rthcId":"RPEP-13377","title":"Orthostatic hypotension after kidney transplantation in a patient with diabetic kidney disease: an underrecognized and therapeutic challenge.","authors":"Sakai, Masafumi; Ogata, Masatomo; Tanabe, Jun; Sakurai, Yuko; Shinoda, Kazunobu; Shibagaki, Yugo; Yazawa, Masahiko","year":2025,"journal":"CEN case reports, 14(6), 837-842","doi":"10.1007/s13730-025-01030-0","pmid":"40892118","tags":["glp1-receptor-agonists","kidney-disease","cardiovascular-outcomes","safety-profile"],"studyType":"case report","evidenceStrength":"very low","keyFinding":"A kidney transplant recipient who lost weight on a GLP-1 drug before surgery developed severe orthostatic hypotension from combined volume depletion and diabetic autonomic dysfunction.","whyItMatters":"As more diabetic patients use GLP-1 drugs before transplant, clinicians should watch for orthostatic hypotension in the post-transplant period when fluid shifts add to pre-existing autonomic problems.","specificNumbers":"1 patient; woman in her 50s; GLP-1 RA-induced weight loss pre-transplant; orthostatic hypotension confirmed 1 month post-transplant; midodrine and fludrocortisone tried without improvement","methodology":"Single case report with clinical description, orthostatic testing, and cardiac autonomic function assessment (CVRR).","limitations":"Single case; cannot generalize. Multiple factors contributed to orthostatic hypotension. GLP-1 drug contribution versus diabetic neuropathy cannot be separated."},{"rthcId":"RPEP-13378","title":"Antimicrobial Peptide-Loaded Mesoporous Silica Nanoparticles: A pH-Triggered Controlled Release against Biofilms.","authors":"Sakaj, Mirena; Lombardi, Vincenzo; Caligiuri, Isabella; Castellin, Andrea; Riello, Pietro","year":2025,"journal":"ACS omega, 10(49), 60142-60151","doi":"10.1021/acsomega.1c04410","pmid":"41427165","tags":["antimicrobial-peptides","drug-delivery-systems","nanotechnology","biofilm"],"studyType":"preclinical study (in vitro)","evidenceStrength":"low (in vitro)","keyFinding":"Mesoporous silica nanoparticles loaded with two antimicrobial peptides released their cargo preferentially at acidic pH (mimicking biofilms) and retained antibacterial activity against S. aureus.","whyItMatters":"Antimicrobial peptides degrade quickly in the body. Encapsulating them in pH-responsive nanoparticles could deliver them specifically to infection sites where conditions are acidic.","specificNumbers":"High loading capacity via electrostatic interactions; minimal release at pH 7.4; significant release at pH 5.5; comparable antibacterial/antibiofilm activity to free peptides against S. aureus","methodology":"Mesoporous silica nanoparticle synthesis and peptide loading. pH-responsive release profiling. In vitro antibacterial and antibiofilm assays against S. aureus. Stability comparison vs free peptides.","limitations":"In vitro only. Single bacterial species tested. Biocompatibility and in vivo distribution not assessed. Release kinetics in complex biological fluids may differ."},{"rthcId":"RPEP-13379","title":"Case Report: A case of occult insulinoma localized by [18F] FB (ePEG12)12-exendin-4 positron emission tomography with negative findings of selective arterial calcium stimulation test.","authors":"Sakaki, Kentaro; Murakami, Takaaki; Fujimoto, Hiroyuki; Shimizu, Yoichi; Miyake, Kanae Kawai; Otani, Daisuke; Otsuki, Shinya; Shimizu, Hironori; Nagai, Kazuyuki; Nomura, Takumi; Yabe, Daisuke; Nakamoto, Yuji; Inagaki, Nobuya","year":2025,"journal":"Frontiers in endocrinology, 16, 1556813","doi":"10.3389/fendo.2025.1556813","pmid":"40405975","tags":["glp1-receptor-agonists","diagnostics","radionuclide-therapy","pancreatic-disorders"],"studyType":"case report","evidenceStrength":"very low","keyFinding":"A GLP-1 receptor-targeted PET scan (18F-exendin-4) found an occult insulinoma that CT, MRI, endoscopic ultrasound, and calcium stimulation testing all missed, enabling curative surgery.","whyItMatters":"Insulinomas are hard to find with standard imaging. GLP-1 receptor PET offers a new non-invasive option that may locate tumors when everything else fails.","specificNumbers":"1 patient; age 67 at onset, 73 at surgery; 6 years on diazoxide; negative on CT, MRI, EUS, and SACST; positive on 18F-exendin-4 PET/CT; complete remission post-surgery","methodology":"Single case report describing diagnostic workup including CT, MRI, EUS, SACST, and 18F-exendin-4 PET/CT, followed by surgical resection and histopathology.","limitations":"Single case. Availability of 18F-exendin-4 PET/CT is very limited. Cost-effectiveness unknown. Cannot determine sensitivity/specificity from one case."},{"rthcId":"RPEP-13380","title":"Grade 3 Pancreatic Neuroendocrine Tumor Refractory to Chemotherapy Successfully Treated with Peptide Receptor Radionuclide Therapy Leading to Conversion Surgery.","authors":"Sakaki, Kotaro; Chiba, Mitsuru; Iijima, Katsunori; Goto, Takashi; Arita, Junichi; Tsuda, Hidehiko","year":2025,"journal":"Internal medicine (Tokyo, Japan), 64(5), 679-685","doi":"10.2169/internalmedicine.3768-24","pmid":"39048369","tags":["somatostatin-analogs","radionuclide-therapy","cancer-immunotherapy","pancreatic-disorders"],"studyType":"case report","evidenceStrength":"very low","keyFinding":"A grade 3 pancreatic neuroendocrine tumor that failed chemotherapy shrank dramatically with peptide receptor radionuclide therapy (PRRT), enabling complete surgical removal and full response.","whyItMatters":"PRRT is usually studied in lower-grade neuroendocrine tumors. This case shows it can rescue even high-grade tumors that resist chemotherapy, making surgery possible.","specificNumbers":"1 patient; grade 3 P-NET, Ki67 25%; failed 6 courses streptozotocin + lanreotide; PRRT as 2nd line; complete response at 6 months post-surgery","methodology":"Single case report describing chemotherapy failure, PRRT response, conversion surgery, and post-operative imaging follow-up.","limitations":"Single case. Grade 3 tumors are heterogeneous. PRRT availability is limited. Cannot predict which high-grade tumors will respond."},{"rthcId":"RPEP-13381","title":"The impact of the conjugation manner of targeting agent and tandem cell-penetrating peptide on the efficacy of mitomycin C liposomes in treating triple-negative breast tumors.","authors":"Salahi, Mehrnaz; Varshosaz, Jaleh; Rostami, Mahboubeh; Esfahani, Salar Nasr; Hekmat, Arsham; Jahanian-Najafaabadi, Ali; Minayian, Mohsen","year":2025,"journal":"International journal of pharmaceutics: X, 10, 100457","doi":"10.1016/j.ijpx.2025.100457","pmid":"41476708","tags":["cell-penetrating-peptides","drug-delivery-systems","cancer-immunotherapy","nanotechnology"],"studyType":"preclinical study (in vitro and in vivo)","evidenceStrength":"low (animal study)","keyFinding":"Liposomes coated with poly-L-arginine (cell-penetrating peptide) and chondroitin sulfate (CD44 targeting) delivered mitomycin C to triple-negative breast tumors in mice, achieving the strongest tumor suppression with a Ki-67 index of just 6%.","whyItMatters":"Triple-negative breast cancer has few treatment options. Combining a tumor-targeting molecule with a cell-penetrating peptide on drug-carrying nanoparticles could improve chemotherapy delivery while reducing side effects.","specificNumbers":"PLA-CS liposomes: 144 nm, 73% encapsulation; Ki-67 index 6% (vs higher in controls); caspase-3 upregulated 13-64 fold; G1 cell cycle arrest; no liver/kidney metastasis; sustained MMC release over 24h","methodology":"Liposome synthesis and characterization (size, PDI, zeta potential, encapsulation). In vitro: MTT cytotoxicity, cellular uptake, apoptosis, cell cycle, qRT-PCR for caspases in 4T1 cells. In vivo: orthotopic 4T1 tumors in BALB/c mice.","limitations":"Mouse tumor model. Single tumor type (4T1). PLA-CS vs CS-PLA order matters for efficacy, adding manufacturing complexity. Long-term safety not assessed."},{"rthcId":"RPEP-13382","title":"On the front lines of cardiovascular-kidney-metabolic syndrome: Review of GLP-1 and Dual GLP-1/GIP receptor agonists in CV and kidney health.","authors":"Salama, Lavinia; Sinn, Levi","year":2025,"journal":"American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists, 82(12), 693-709","doi":"10.1093/ajhp/zxaf053","pmid":"40197714","tags":["glp1-receptor-agonists","gip","cardiovascular-outcomes","kidney-disease","clinical-guidelines"],"studyType":"narrative review","evidenceStrength":"low (review of field)","keyFinding":"GLP-1 RAs and dual GLP-1/GIP agonists reduce cardiovascular events and preserve kidney function beyond glucose control, with expanding indications for CKM syndrome even without diabetes.","whyItMatters":"Cardiovascular-kidney-metabolic syndrome is a newly defined framework linking heart, kidney, and metabolic disease. GLP-1 drugs address all three components simultaneously.","specificNumbers":"Significant CV event reduction and kidney function preservation in multiple RCTs; KDIGO and ADA guideline-endorsed","methodology":"Narrative review of RCTs, guidelines (KDIGO, ADA), and emerging evidence for GLP-1 RAs and GLP-1/GIP agonists in CKM syndrome.","limitations":"Narrative format without systematic methodology. Some indications discussed are not yet FDA-approved. Pharmacist role recommendations may vary by healthcare setting."},{"rthcId":"RPEP-13383","title":"Updates on Anti-Obesity Medications in Children and Adolescents.","authors":"Salama, Mostafa; Hassan, Doha; Kumar, Seema","year":2025,"journal":"Children (Basel, Switzerland), 12(10)","doi":"10.3390/children12101390","pmid":"41153573","tags":["glp1-receptor-agonists","obesity","pediatric-studies","weight-management"],"studyType":"narrative review","evidenceStrength":"low (review of field)","keyFinding":"GLP-1 receptor agonists show promise in adolescents with obesity, but pharmacologic options remain limited for younger children. Lifestyle modification alone produces modest results.","whyItMatters":"Childhood obesity has reached epidemic levels with serious health consequences. Age-appropriate drug treatment strategies are needed alongside lifestyle changes.","specificNumbers":"Childhood obesity at epidemic levels; pharmacotherapy recommended as adjunct for severe/refractory pediatric obesity; limited options for children under 12","methodology":"Narrative review of efficacy and safety evidence for anti-obesity medications in children and adolescents.","limitations":"Narrative format. Most drug trials are in adolescents 12+. Long-term safety data in pediatric populations are limited. Guidelines vary by country."},{"rthcId":"RPEP-13384","title":"Endometrial Transcriptome Changes following Short-Term Liraglutide Treatment in Infertile Women with Polycystic Ovarian Syndrome and Obesity.","authors":"Salamun, Vesna; Lovrecic, Luca; Maver, Ales; Peterlin, Borut; Ban Frangez, Helena; Riemma, Gaetano; Laganà, Antonio Simone; Herman, Rok; Janez, Andrej; Vrtacnik Bokal, Eda; Jensterle, Mojca","year":2025,"journal":"Gynecologic and obstetric investigation, 1-10","doi":"10.1159/000547513","pmid":"40695252","tags":["glp1-receptor-agonists","liraglutide","reproductive-health","genomics"],"studyType":"cross-sectional genomic study","evidenceStrength":"low","keyFinding":"12 weeks of liraglutide changed endometrial gene expression in 17 key pathways, including GLP-1 receptor activation, inflammation modulation, and glucose metabolism, potentially improving uterine receptivity for IVF.","whyItMatters":"Many obese women with PCOS struggle with infertility partly due to poor endometrial receptivity. If GLP-1 drugs improve the uterine lining, they could help before IVF.","specificNumbers":"20 women (10 treated, 10 controls); liraglutide 1.2 mg daily x 12 weeks; 5%+ weight loss required; 17 differentially expressed pathways; YWHAG identified as central network gene","methodology":"Cross-sectional study comparing endometrial biopsies during the implantation window. Next-generation RNA sequencing. Gene set analysis for canonical pathways and network construction.","limitations":"Cross-sectional, not randomized. Very small sample (n=20). Cannot establish causation. Weight loss itself may explain some endometrial changes. Many genes up/down regulated makes interpretation complex."},{"rthcId":"RPEP-13385","title":"Harnessing Machine Learning Approaches for the Identification, Characterization, and Optimization of Novel Antimicrobial Peptides.","authors":"Saleem, Naveed; Kumar, Naresh; El-Omar, Emad; Willcox, Mark; Jiang, Xiao-Tao","year":2025,"journal":"Antibiotics (Basel, Switzerland), 14(12)","doi":"10.3390/antibiotics14121263","pmid":"41463765","tags":["antimicrobial-peptides","artificial-intelligence","peptide-drug-design","antimicrobial-resistance"],"studyType":"narrative review","evidenceStrength":"low (review of field)","keyFinding":"AI and machine learning can now screen vast peptide sequence spaces to predict antimicrobial activity, toxicity, and stability, dramatically improving hit rates for novel AMP discovery.","whyItMatters":"Antimicrobial resistance may cause more deaths than cancer by 2050. AI-driven peptide design could accelerate discovery of new antibiotics that work through resistance-proof mechanisms.","specificNumbers":"AMR projected to surpass cancer as leading cause of death by 2050; ~100 peptides clinically approved; AI methods improve experimental hit rates","methodology":"Narrative review of machine learning, deep learning, transformer, and generative AI approaches for AMP identification, prediction, and de novo design.","limitations":"Narrative format. Many AI-designed peptides lack in vivo validation. Computational predictions do not always translate to real-world activity. Data quality and standardization remain challenges."},{"rthcId":"RPEP-13386","title":"Neuroprotective effects of semaglutide and metformin against rotenone-induced neurobehavioral changes in male diabetic rats.","authors":"Salem, Esraa A; Alqahtani, Saad Misfer; El-Shoura, Ehab A M; Zaghlool, Sameh S; Abdelzaher, Lobna A; Mohamed, Sally A M; Alalhareth, Ibrahim S; Sheref, Alzahraa A M","year":2025,"journal":"Naunyn-Schmiedeberg's archives of pharmacology, 398(9), 11919-11931","doi":"10.1007/s00210-025-03920-7","pmid":"40088335","tags":["glp1-receptor-agonists","semaglutide","neuroprotection","neurological-disorders","type-2-diabetes"],"studyType":"preclinical study (animal model)","evidenceStrength":"low (animal study)","keyFinding":"Semaglutide and metformin together protected rat brains better than either drug alone in a combined diabetes-Parkinsons model, reducing oxidative stress, inflammation, and nerve cell death.","whyItMatters":"People with diabetes have higher Parkinsons risk. Finding that two common diabetes drugs work together to protect the brain could lead to combination strategies for prevention.","specificNumbers":"4 weeks treatment; improved blood glucose, HOMA-IR, HbA1c, cholesterol, triglycerides, LDL; increased insulin, HDL; downregulated caspase 3 and GFAP; upregulated Nrf2; improved cognition, locomotion, and olfaction","methodology":"Rat model: HFD + STZ for T2DM, rotenone for PD. Met and/or semaglutide by gastric gavage for 4 weeks. Behavioral tests (cognitive, locomotor, olfactory). Biochemical markers. Western blot for caspase 3, GFAP, Nrf2.","limitations":"Rat model may not translate to humans. Combined disease induction is artificial. 4-week treatment is short. Gavage delivery differs from clinical use. Small group sizes typical of animal studies."},{"rthcId":"RPEP-13387","title":"Evaluation of the Therapeutic Potential of Synthetic Growth Hormone-Releasing Hormone Antagonist MIA-690 as a Cognitive Modulator in a Mouse Model of Gulf War Illness.","authors":"Salgueiro-Tosta, Luis Manuel; Jayakumar, Arumugam Radhakrishnan; Kochen, William; Cai, Renzhi; Sha, Wei; Johnson, Erik; O'Callaghan, James; Jászberényi, Miklós; Schally, Andrew Victor; Klimas, Nancy","year":2025,"journal":"International journal of molecular sciences, 26(17)","doi":"10.3390/ijms26178516","pmid":"40943436","tags":["growth-hormone-releasing-hormone","neuroprotection","hormone-regulation"],"studyType":"preclinical study (animal model)","evidenceStrength":"low (animal study)","keyFinding":"The GHRH antagonist MIA-690 selectively improved learning efficiency in female mice with experimental Gulf War illness but did not improve other cognitive or behavioral measures.","whyItMatters":"Gulf War illness affects many veterans with no effective treatment. Targeting the stress hormone axis with peptide antagonists is a novel approach, though results here were limited.","specificNumbers":"10 mcg MIA-690 subcutaneous daily x 10 days; improved learning in females on Morris water maze; no effect on NOR, OFT, GST; GWI model: CORT + DFP + LPS exposure","methodology":"Mouse GWI model (CORT + DFP, then CORT + LPS). MIA-690 10 mcg SC daily x 10 days. Behavioral testing: Morris water maze, novel object recognition, grip strength, open field test.","limitations":"Single dose tested. Short treatment duration (10 days). Sex-specific effect only in one test. Mouse model may not fully replicate human GWI. Small sample sizes."},{"rthcId":"RPEP-13388","title":"B-Type Natriuretic Peptides Levels in Patients With Beta-Thalassemia Major and Correlations With Biomarkers: A Systematic Review and Meta-Analysis.","authors":"Salih, Mohamed S K; Mohamed, Amna H; Mirghani, Elsara M A; Makki, Mohammed Y K; Ahmed, Ola A M; Mohammed, Esraa T S; Hassan, Hana H M; Omar, Nada; Garalnabi, Esraa M A; Mohamed, Sagad O O","year":2025,"journal":"Health science reports, 8(11), e71493","doi":"10.1002/hsr2.71493","pmid":"41221424","tags":["biomarkers","cardiovascular-outcomes","natriuretic-peptides"],"studyType":"systematic review and meta-analysis","evidenceStrength":"strong","keyFinding":"Both BNP and NT-proBNP are significantly elevated in beta-thalassemia major patients. NT-proBNP correlates with serum ferritin, E/E ratio, and cardiac T2* MRI values.","whyItMatters":"Thalassemia patients get repeated blood transfusions that damage the heart with iron overload. BNP blood tests could catch heart damage early, before symptoms appear.","specificNumbers":"29 studies reviewed, 27 in meta-analysis; NT-proBNP SMD 1.37 (95% CI 0.856-1.893); correlated with ferritin (r=0.471), E/E (r=0.528), T2* (r=0.259)","methodology":"Systematic review per PRISMA guidelines. PubMed, Web of Science, ScienceDirect searched. Meta-analysis of standardized mean differences and correlation coefficients.","limitations":"High heterogeneity across studies. Most studies used NT-proBNP, limiting BNP-specific conclusions. Observational data; correlations do not prove causation. Different assays used across studies."},{"rthcId":"RPEP-13389","title":"Efficacy and Tolerability of Anti-CGRP Monoclonal Antibodies in Patients Aged ≥ 65 Years With Daily or Nondaily Migraine.","authors":"Salim, Amira; Biswas, Sudipa; Sonneborn, Claire; Hogue, Olivia; Hennessy, Elise; Mays, Maryann; Suneja, Aarushi; Ahmed, Zubair; Mata, Ignacio F","year":2025,"journal":"Neurology. Clinical practice, 15(1), e200373","doi":"10.1212/CPJ.0000000000200373","pmid":"39399553","tags":["cgrp","neuropeptides","neurological-disorders","aging"],"studyType":"retrospective observational study","evidenceStrength":"moderate","keyFinding":"Anti-CGRP monoclonal antibodies reduced migraine days equally well in patients 65 and older compared to younger patients, with fewer side effects reported in the older group.","whyItMatters":"Older adults with migraine are often excluded from clinical trials. This real-world study shows CGRP antibodies are effective and well-tolerated in this underserved population.","specificNumbers":"n=2,707 under 65, n=304 aged 65+; median 10 MMD reduction in both groups (p=0.57); side effects 22% vs 28% (O65 vs U65); injection site reaction 40%, constipation 25%; 50% responder rate: 67% nondaily vs 54% daily","methodology":"Retrospective review of electronic medical records from June 2018 to November 2021. Mann-Whitney tests comparing efficacy and tolerability between age groups, overall and stratified by daily vs nondaily migraine.","limitations":"Retrospective design with potential selection bias. Single-center or network not specified. Older patients in clinical practice may be healthier than the general elderly population. No long-term follow-up data."},{"rthcId":"RPEP-13390","title":"The role and interaction of hypothalamic-related neurotransmitters in migraine.","authors":"Salinas-Abarca, Ana Belen; Gamal-Eltrabily, Mohammed; Romero-Reyes, Marcela; Akerman, Simon","year":2025,"journal":"The journal of headache and pain, 26(1), 110","doi":"10.1186/s10194-025-02044-w","pmid":"40350428","tags":["neuropeptides","neurological-disorders","hormone-regulation","orexins"],"studyType":"narrative review","evidenceStrength":"low (review of field)","keyFinding":"The hypothalamus is a central hub for migraine, producing neuropeptides (orexins, NPY, PACAP, oxytocin, vasopressin) that modulate migraine through interactions with sex hormones, stress, and circadian rhythms.","whyItMatters":"Migraine triggers like stress, missed meals, and sleep disruption all act through the hypothalamus. Targeting hypothalamic neuropeptides could yield more precise migraine therapies.","specificNumbers":"Migraine prevalence higher in women; hypothalamic neuropeptides: orexins, NPY, PACAP, oxytocin, vasopressin all implicated","methodology":"Narrative review of hypothalamic contributions to migraine, covering neuropeptides, sex hormones, stress, feeding, and sleep pathways.","limitations":"Narrative format without systematic search. Most mechanistic evidence from animal models. Clinical translation of hypothalamic targeting is still theoretical."},{"rthcId":"RPEP-13391","title":"Cathelicidin-BF: A Potent Antimicrobial Peptide Leveraging Charge and Phospholipid Recruitment against Multidrug-Resistant Clinical Bacterial Isolates.","authors":"Salnikov, Evgeniy; Adélaïde, Morgane; Ramos-Martín, Francisco; Saad, Ahmad; Schauer, Jennifer; Cremanns, Martina; Rima, Mariam; Aisenbrey, Christopher; Oueslati, Saoussen; Naas, Thierry; Pfennigwerth, Niels; Gatermann, Söeren; Sarazin, Catherine; Bechinger, Burkhard; D'Amelio, Nicola","year":2025,"journal":"Journal of the American Chemical Society, 147(13), 11199-11215","doi":"10.1021/jacs.4c17821","pmid":"40126422","tags":["antimicrobial-peptides","ll-37-cathelicidin","antimicrobial-resistance","membrane-interactions"],"studyType":"laboratory study","evidenceStrength":"low (in vitro with some in vivo)","keyFinding":"Cathelicidin-BF killed carbapenem-resistant bacteria at concentrations as low as 0.5 micromolar, unaffected by resistance mechanisms or Gram type. It works by neutralizing and perforating bacterial membranes.","whyItMatters":"Drug-resistant hospital infections kill hundreds of thousands yearly. CatBF works through a mechanism bacteria have not evolved resistance to, making it a strong candidate for development.","specificNumbers":"MICs as low as 0.5 microM against carbapenem-resistant A. baumannii, K. pneumoniae, E. coli; tested against 81 clinical isolates; serum half-life at least 1 hour; LL-37 homolog","methodology":"MIC testing against 81 multidrug-resistant clinical isolates. NMR spectroscopy for structure. Paramagnetic probes and molecular dynamics for membrane interaction. Multiple membrane models tested.","limitations":"In vitro antimicrobial data. In vivo efficacy referenced but not detailed in abstract. Snake-derived peptide may need modification for clinical use. Manufacturing scalability unclear."},{"rthcId":"RPEP-13392","title":"Prostaglandin E2 as a Mechanistic Biomarker of Chronic Pancreatitis.","authors":"Saloman, Jami L; Jefferson, Bahiyyah; Han, Samuel; Fisher, William E; Fogel, Evan L; Hart, Phil A; Li, Liang; Park, Walter G; Vege, Santhi Swaroop; Yadav, Dhiraj; Topazian, Mark D; Conwell, Darwin L","year":2025,"journal":"Clinical and translational gastroenterology, 16(10), e00897","doi":"10.14309/ctg.0000000000000897","pmid":"40758192","tags":["biomarkers","cgrp","neuropeptides","pancreatic-disorders","inflammation"],"studyType":"cross-sectional biomarker study","evidenceStrength":"moderate","keyFinding":"PGE2 in pancreatic fluid did not reliably distinguish chronic pancreatitis from acute/recurrent pancreatitis. However, MMP7 and MMP9 were significantly elevated in chronic pancreatitis and may serve as staging biomarkers.","whyItMatters":"Chronic pancreatitis is hard to diagnose early when intervention could prevent irreversible damage. Finding that MMPs outperform PGE2 redirects biomarker research toward more promising targets.","specificNumbers":"Pancreatic fluid: n=110 (0-10 min), n=111 (10-20 min); plasma n=75; urine n=71; PGE2 lower in AP/RAP vs controls (p=0.027 fluid, p=0.046 plasma); MMP7 elevated in CP vs AP/RAP (p=0.012); MMP9 elevated in CP (p=0.027, p=0.002)","methodology":"Cross-sectional study from PROCEED cohort. Pancreatic fluid collected after IV secretin at 0-10 and 10-20 minute intervals. PGE2, CGRP, substance P, and MMPs measured. Three-group comparison.","limitations":"Cross-sectional design cannot track disease progression. PGE2 did not meet primary objective. Small subgroup sizes. Secretin stimulation protocol adds complexity. CGRP/substance P results not detailed."},{"rthcId":"RPEP-13393","title":"Decoupling Bioactivity and Processability: RGD Click-Functionalized Coatings for a 3D-Printed PCL Scaffold.","authors":"Salsano, Giulia; Sardo, Carla; Guidone, Angiola; Coppola, Pierpaolo; Sala, Marina; Scala, Maria Carmina; Soriente, Alessandra; Raucci, Maria Grazia; Aquino, Rita Patrizia; Auriemma, Giulia","year":2025,"journal":"Biomacromolecules, 26(11), 8234-8245","doi":"10.1021/acs.biomac.5c01691","pmid":"41066249","tags":["peptide-drug-design","tissue-engineering","biomaterials"],"studyType":"preclinical study (in vitro)","evidenceStrength":"low (in vitro)","keyFinding":"3D-printed bone scaffolds coated with an RGD peptide improved cell adhesion and mineralization compared to uncoated scaffolds, while preserving mechanical properties.","whyItMatters":"Bone implants often lack the biological signals cells need to attach and grow. Adding peptides to the surface after printing keeps manufacturing simple while adding biological function.","specificNumbers":"RGD peptide conjugated via thiol-maleimide click chemistry; coating confirmed by NMR, FTIR, DSC, GPC, SEM-EDX; improved SAOS-2 adhesion and mineralization vs controls","methodology":"Three-step PCL modification to introduce maleimide groups, then thiol-maleimide conjugation with RGD peptide. Dip-coating onto 3D-printed PCL scaffolds. Characterization by multiple analytical methods. In vitro cell adhesion and mineralization assays with SAOS-2 cells.","limitations":"In vitro only with one cell line. No in vivo bone healing data. Coating durability under mechanical loading not tested. Single peptide tested; other bioactive peptides may further improve results."},{"rthcId":"RPEP-13394","title":"GLP-1-based medications: Mechanisms involved in obesity treatment.","authors":"Salvador, Javier","year":2025,"journal":"Medicina clinica, 165(1), 107035","doi":"10.1016/j.medcli.2025.107035","pmid":"40466247","tags":["glp1-receptor-agonists","obesity","gip","glucagon","weight-management"],"studyType":"narrative review","evidenceStrength":"low (review of field)","keyFinding":"GLP-1 agonists and multiagonists now achieve up to 24% weight loss by addressing multiple obesity mechanisms: appetite regulation, adipocyte dysfunction, insulin resistance, inflammation, and endothelial dysfunction.","whyItMatters":"Obesity is not just about eating too much. GLP-1 drugs tackle the underlying biological processes driving complications like fatty liver disease, heart failure, and atherosclerosis.","specificNumbers":"Up to 24% weight loss with multiagonists; mechanisms include appetite, adipocyte dysfunction, insulin resistance, adipokines, inflammation, endothelial function, lipid metabolism, oxidative stress","methodology":"Narrative review of GLP-1 agonist mechanisms in obesity and its complications, covering mono- and multi-agonist approaches.","limitations":"Narrative format without systematic search. Some multiagonists are still in clinical trials. Mechanisms discussed are from mixed preclinical and clinical evidence."},{"rthcId":"RPEP-13395","title":"Semaglutide as a GLP-1 Agonist: A Breakthrough in Obesity Treatment.","authors":"Salvador, Rui; Moutinho, Carla Guimarães; Sousa, Carla; Vinha, Ana Ferreira; Carvalho, Márcia; Matos, Carla","year":2025,"journal":"Pharmaceuticals (Basel, Switzerland), 18(3)","doi":"10.3390/ph18030399","pmid":"40143174","tags":["glp1-receptor-agonists","semaglutide","obesity","type-2-diabetes","weight-management"],"studyType":"narrative review","evidenceStrength":"low (review of field)","keyFinding":"Semaglutide achieves superior weight loss versus other GLP-1 drugs across SUSTAIN, PIONEER, and STEP trials. Oral semaglutide at 50 mg approaches injectable efficacy.","whyItMatters":"Semaglutide has become the benchmark GLP-1 drug. Understanding its evidence base across multiple trial programs helps clinicians and patients make informed treatment decisions.","specificNumbers":"SUSTAIN, PIONEER, and STEP trial programs; oral 50 mg approaches subcutaneous efficacy; superior to other GLP-1 RAs and anti-obesity drugs in head-to-head comparisons","methodology":"Narrative review of semaglutide clinical trial programs (SUSTAIN, PIONEER, STEP) and its pharmacology, efficacy, and safety.","limitations":"Narrative format without systematic methodology. Weight regain after cessation not fully addressed. Individual response variability not well characterized. Some trial data are from manufacturer-sponsored studies."},{"rthcId":"RPEP-13396","title":"Real-world comparative outcomes of GLP-1 RA and semaglutide prescription among individuals with type 2 diabetes.","authors":"Salvatore, Maxwell; Zhang, Bingyu; Tang, Huilin; Lu, Yiwen; Zhang, Dazheng; Zhou, Ting; Lu, Yuan; Amaro, Anastassia; Ritchie, Marylyn; Chen, Yong","year":2025,"journal":"medRxiv : the preprint server for health sciences","doi":"10.1101/2025.06.03.25328908","pmid":"40502555","tags":["glp1-receptor-agonists","semaglutide","type-2-diabetes","safety-profile","sglt2-inhibitors"],"studyType":"phenome-wide association study (observational)","evidenceStrength":"moderate","keyFinding":"Semaglutide was linked to lower risks of cardiac arrhythmia, hyperglycemia, and chronic kidney disease compared to other diabetes drugs. GLP-1 RAs overall showed reduced genitourinary and dental conditions but increased risks of dysthymia and vitamin D deficiency.","whyItMatters":"This broad-spectrum analysis of real-world outcomes reveals both expected benefits and unexpected associations that targeted trials would miss.","specificNumbers":"n=18,746 from All of Us; semaglutide-specific analyses vs SGLT2i and DPP4i; reduced arrhythmia, hyperglycemia, CKD; increased dysthymia, vitamin D deficiency","methodology":"Phenome-wide association study using All of Us Research Program data. Intention-to-treat and per-protocol analyses comparing diagnoses after GLP-1 RA, SGLT2i, or DPP4i initiation. Time-to-event analyses.","limitations":"Preprint (not peer-reviewed). Observational associations, not causation. Multiple comparisons increase false positive risk. Claims data may misclassify diagnoses."},{"rthcId":"RPEP-13397","title":"Effects of glucagon-like peptide 1 receptor agonists on testicular dysfunction: A systematic review and meta-analysis.","authors":"Salvio, Gianmaria; Ciarloni, Alessandro; Ambo, Nicola; Bordoni, Monia; Perrone, Michele; Rossi, Silvia; Balercia, Giancarlo","year":2025,"journal":"Andrology, 13(8), 2022-2034","doi":"10.1111/andr.70022","pmid":"40105090","tags":["glp1-receptor-agonists","hormone-regulation","obesity","reproductive-health"],"studyType":"systematic review and meta-analysis","evidenceStrength":"moderate","keyFinding":"GLP-1 receptor agonists raised total testosterone by 1.39 ng/mL in overweight/obese men, with corresponding increases in free testosterone, SHBG, LH, and FSH. The testosterone increase correlated with weight loss.","whyItMatters":"Low testosterone in obese men is a common but underrecognized problem. If GLP-1 drugs can restore testosterone levels through weight loss, they could treat both obesity and functional hypogonadism simultaneously.","specificNumbers":"7 studies; n=680; total testosterone +1.39 ng/mL (95% CI 0.70-2.09, p<0.0001); significant increases in FT, SHBG, LH, FSH; significant decreases in weight, BMI, WC, HbA1c","methodology":"Systematic review of PubMed, EMBASE, Scopus. Meta-analysis with before-after and comparative analyses. Meta-regression for testosterone vs weight/BMI change.","limitations":"Only 7 studies available; small total sample. Cannot distinguish direct gonadal effects from indirect weight-loss effects. Heterogeneous study designs and GLP-1 drugs used."},{"rthcId":"RPEP-13398","title":"Glucagon-like Peptide-1 Receptor Agonists in the Management of Diabetic Retinopathy.","authors":"Samanta, Anindya; Bordbar, Darius D; Weng, Christina Y; Chancellor, John R","year":2025,"journal":"International ophthalmology clinics, 65(1), 23-26","doi":"10.1097/IIO.0000000000000541","pmid":"39710901","tags":["glp1-receptor-agonists","semaglutide","type-2-diabetes","safety-profile"],"studyType":"clinical review","evidenceStrength":"low (review of field)","keyFinding":"GLP-1 receptor agonists may worsen diabetic retinopathy in some patients, especially semaglutide, likely from rapid blood sugar improvement. The cardiovascular benefits outweigh this risk when ophthalmology follow-up is maintained.","whyItMatters":"Eye doctors are seeing more patients on GLP-1 drugs. Knowing that rapid glycemic improvement can temporarily worsen retinopathy helps plan monitoring and prevents unnecessary drug discontinuation.","specificNumbers":"Some worsening of diabetic retinopathy noted in studies, particularly with semaglutide; macrovascular benefits prioritized over microvascular risk","methodology":"Brief clinical review of GLP-1 RA effects on diabetic retinopathy, covering trial data and clinical recommendations.","limitations":"Brief review without systematic methodology. Retinopathy worsening data come from subgroup analyses of larger trials. Mechanism not fully established."},{"rthcId":"RPEP-13399","title":"The Road to the Full Sequencing of Natural Frogs' Peptides Relying Solely on Mass Spectrometry.","authors":"Samgina, T Yu; Lebedev, A T","year":2025,"journal":"Mass spectrometry (Tokyo, Japan), 14(1), A0182","doi":"10.5702/massspectrometry.A0182","pmid":"41459570","tags":["antimicrobial-peptides","peptide-drug-design","analytical-methods"],"studyType":"methodology review","evidenceStrength":"low (review of analytical methods)","keyFinding":"Modern mass spectrometry can now fully sequence all frog antimicrobial peptides (up to 46 amino acids) de novo, including distinguishing leucine from isoleucine, without any preliminary chemical treatment.","whyItMatters":"Frog skin peptides are a rich source of potential antibiotics. Being able to sequence them completely using just mass spectrometry speeds up discovery of new antimicrobial candidates.","specificNumbers":"Peptides up to 46 amino acids fully sequenced; 30+ years of mass spectrometry development; EThcD and ExD resolve leucine/isoleucine","methodology":"Review of de novo mass spectrometry sequencing algorithms for amphibian peptides, including accurate mass measurement, EThcD, and ExD fragmentation approaches.","limitations":"Methodology review, not a study of biological activity. Focuses on sequencing rather than functional characterization. Some specialized instruments may not be widely available."},{"rthcId":"RPEP-13400","title":"A Contemporary Rationale for Agonism of the GIP Receptor in the Treatment of Obesity.","authors":"Samms, Ricardo J; Sloop, Kyle W","year":2025,"journal":"Diabetes, 74(8), 1326-1333","doi":"10.2337/dbi24-0026","pmid":"40521890","tags":["gip","glp1-receptor-agonists","tirzepatide","obesity","insulin-signaling"],"studyType":"perspective/opinion article","evidenceStrength":"low (expert opinion with data review)","keyFinding":"GIP receptor agonism reduces nausea, suppresses appetite centrally, and promotes healthy fat storage in adipose tissue. These effects explain why dual GIP/GLP-1 agonists like tirzepatide outperform GLP-1-only drugs.","whyItMatters":"There is debate about whether GIP receptors should be activated or blocked for obesity treatment. This article argues activation is better because it improves fat distribution and reduces side effects.","specificNumbers":"GIP identified as the primary incretin; tirzepatide activates both GIPR and GLP-1R; GIPR agonism reduces nausea and suppresses appetite in CNS","methodology":"Perspective article reviewing GIP receptor physiology in islets, CNS, and adipose tissue with interpretation of preclinical and clinical data.","limitations":"Opinion/perspective piece. Some claims are based on animal data. The GIPR agonism vs antagonism debate is not settled. Head-to-head data comparing agonist and antagonist approaches are limited."},{"rthcId":"RPEP-13401","title":"Real-world titration, persistence & weight loss of semaglutide and tirzepatide in an academic obesity clinic.","authors":"Samuels, Jason M; Ye, Fei; Irlmeier, Rebecca; Silver, Heidi; Srivastava, Gitanjali; Spann, Matthew","year":2025,"journal":"Diabetes, obesity & metabolism, 27(11), 6200-6209","doi":"10.1111/dom.70004","pmid":"40762026","tags":["glp1-receptor-agonists","semaglutide","tirzepatide","obesity","weight-management"],"studyType":"retrospective cohort study","evidenceStrength":"moderate","keyFinding":"In a multidisciplinary obesity clinic with free medication access, patients persistent on GLP-1 drugs for 12+ months lost a median of 14.4% body weight. Only 23% of semaglutide users reached the 2.4 mg dose.","whyItMatters":"Real-world weight loss often falls short of trials. This study shows that in optimal conditions (free meds, multidisciplinary support), results approach trial-level outcomes despite suboptimal dose titration.","specificNumbers":"2,306 patients; median persistence 10.7 mo; 6+ mo: -9.4% weight; 12+ mo: -14.4% weight; 81% semaglutide users reached 1+ mg, 23% reached 2.4 mg; 75% tirzepatide users reached 10+ mg, 28% reached 15 mg","methodology":"Single-center retrospective cohort. Consecutive patients in a no-cost medication program. Persistence defined as continuous fills without 84+ day gap. Weight change by persistence duration.","limitations":"Single center with free medication, limiting generalizability. Retrospective design. No control group. Patients who discontinued early not fully analyzed. Mostly female and White population."},{"rthcId":"RPEP-13402","title":"SAFE-CGRP study: multicenter retrospective evaluation of the safety of CGRP pathway-targeting monoclonal antibodies in migraine with relevant comorbidities or conditions excluded from trials.","authors":"Sanabria-Gago, Cristina; Lázaro, Iris Fernández; Heredia, Patricia; Sánchez-Soblechero, Antonio; Ros, Alberto Lozano; Buzo, Elisa Luque; Osorio, Yesica González; Guerrero-Peral, Ángel; Gonzalez-Martinez, Alicia; Azorín, David García; Latorre, Germán; Calle, Carlos; Toledo-Alfocea, Daniel; Limón, Javier Casas; Valle, Sarai Urtiaga; Salaices, Marta González; Ávila, Guillermo Martín; Carpio, Rodrigo Terrero; Pascual, Julio; González-Quintanilla, Vicente; Madera, Jorge; Polanco, Marcos; Rodríguez-Vico, Jaime; Jaimes, Alex; García, Andrea Gómez; Cuadrado, María-Luz; Gago-Veiga, Ana Beatriz","year":2025,"journal":"Frontiers in neurology, 16, 1703876","doi":"10.3389/fneur.2025.1703876","pmid":"41383230","tags":["cgrp","neuropeptides","neurological-disorders","safety-profile"],"studyType":"retrospective multicenter study","evidenceStrength":"moderate","keyFinding":"Anti-CGRP antibodies were safe in 353 migraine patients with complex comorbidities excluded from trials. Only 14 cases showed possible drug-related worsening (mainly Raynaud and hypertension), all reversible on discontinuation.","whyItMatters":"Clinical trials excluded patients with autoimmune diseases, cardiovascular risk, cancer history, and immunosuppression. This study fills that safety gap for real-world prescribing.","specificNumbers":"353 patients with comorbidities from 2,042 total; mean treatment 12.7 months; 14 possible drug-related events (7 Raynaud, 4 hypertension, 2 arthritis, 1 angioedema); 0 serious AEs; 53 comorbidity types represented","methodology":"Retrospective multicenter study across 11 Spanish headache units. Patients with trial-excluded comorbidities who received anti-CGRP or anti-CGRP receptor mAbs. Safety outcomes tracked.","limitations":"Retrospective design with possible underreporting. No control group. 12.7 months average follow-up may miss longer-term effects. Spanish population may not generalize globally."},{"rthcId":"RPEP-13403","title":"Central administration of galanin-like peptide (GALP) causes short-term orexigenic effects in broilers: Mediatory role of NPY1 and D1 receptors.","authors":"Sanadgol, Elham; Zendehdel, Morteza; Vazir, Bita; Rassouli, Ali; Haghbinnazarpak, Hadi","year":2025,"journal":"Neuroscience letters, 844, 138042","doi":"10.1016/j.neulet.2024.138042","pmid":"39551101","tags":["neuropeptides","appetite-regulation","neuropeptide-y","hormone-regulation"],"studyType":"preclinical study (animal model)","evidenceStrength":"low (animal study)","keyFinding":"Galanin-like peptide (GALP) increased food intake in broiler chicks through NPY1 and D1 dopamine receptors. Blocking NPY1 suppressed the effect; blocking D1 enhanced it.","whyItMatters":"Understanding how appetite-regulating peptides interact with dopamine and NPY systems in poultry could improve feed efficiency and reveal conserved mechanisms relevant to human appetite research.","specificNumbers":"GALP doses: 0.5, 1, 2 mcg; 1 and 2 mcg increased food intake (p<0.05); NPY1 antagonist (BIBO-3304) blocked effect; D1 antagonist (SCH39166) enhanced effect; NPY2, NPY5, D2 antagonists had no effect","methodology":"Central (intracerebroventricular) peptide and antagonist administration in broiler chicks. Cumulative food intake measured over 2 hours. Behavioral observations for 30 minutes. Six experiments testing different receptor antagonist combinations.","limitations":"Poultry model; brain peptide pathways may differ from mammals. Acute single-injection protocol. Central administration bypasses normal delivery. Small sample sizes typical of poultry neuroscience."},{"rthcId":"RPEP-13404","title":"In vitro study of antifungal effects of earthworm coelomic fluid obtained from Eisenia fetida on three opportunistic fungal pathogens.","authors":"Sanaiirad, Saeed; Seifi, Mehrdad; Hemmati, Negar; Khosravi, Alireza; Nikaein, Donya","year":2025,"journal":"Current medical mycology, 11","doi":"10.22034/cmm.2025.345248.1637","pmid":"41695225","tags":["antimicrobial-peptides","antifungal-peptides","bioactive-peptides"],"studyType":"laboratory study","evidenceStrength":"low (in vitro)","keyFinding":"Earthworm coelomic fluid extract (60% protein) inhibited Candida albicans (MIC 3.125%) and Aspergillus fumigatus (MIC 12.5%) but was less effective against Cryptococcus neoformans and weaker than itraconazole.","whyItMatters":"With antifungal resistance growing, natural peptide-rich extracts from earthworms could inspire new antifungal agents, though they need significant potency improvement.","specificNumbers":"Extract: 60.03% protein; MIC/MFC for C. albicans: 3.125%/6.25%; A. fumigatus: 12.5%/25%; itraconazole outperformed extract against all strains","methodology":"Earthworm coelomic fluid extraction via electroporation. Composition analysis (Bradford, Kjeldahl, Soxhlet). Disk diffusion and broth microdilution for MIC/MFC against three fungal species.","limitations":"Crude extract, not purified peptides. MIC values expressed as percentages of extract, not molar concentrations. Single earthworm species. In vitro only."},{"rthcId":"RPEP-13405","title":"Preserving the Metabolic Engine: Muscle as the Therapeutic Target for Cardiovascular Prevention in Obesity Pharmacotherapy.","authors":"Sanchis-Gomar, Fabian; Neeland, Ian J; Ruiz-Lozano, Pilar; Alnahar, Osama; Rodriguez, Fatima","year":2025,"journal":"Current cardiology reports, 28(1), 2","doi":"10.1007/s11886-025-02334-4","pmid":"41400708","tags":["glp1-receptor-agonists","obesity","muscle-wasting","cardiovascular-outcomes"],"studyType":"narrative review","evidenceStrength":"low (review of field)","keyFinding":"25-40% of weight lost with incretin therapies comes from lean mass. Exercise, high protein intake, creatine, myostatin inhibitors, and SARMs may help preserve muscle during treatment.","whyItMatters":"Muscle is the bodys metabolic engine. Losing too much muscle during weight loss can undermine the cardiovascular benefits these drugs provide.","specificNumbers":"25-40% of weight loss from lean mass; exercise, protein, creatine as established interventions; myostatin/activin inhibitors and SARMs in early trials","methodology":"Narrative review of lean mass changes during incretin-based weight loss therapy, covering body composition data and muscle preservation strategies.","limitations":"Narrative format. Most data on muscle preservation strategies are from obesity/aging populations, not specifically GLP-1 drug users. Myostatin inhibitors and SARMs are investigational."},{"rthcId":"RPEP-13406","title":"Design of self-emulsifying oral delivery systems for semaglutide: reverse micelles versus hydrophobic ion pairs.","authors":"Sandmeier, Matthias; Ricci, Fabrizio; To, Dennis; Lindner, Sera; Stengel, Daniel; Schifferle, Michaela; Koz, Saadet; Bernkop-Schnürch, Andreas","year":2025,"journal":"Drug delivery and translational research, 15(6), 2146-2161","doi":"10.1007/s13346-024-01729-0","pmid":"39427069","tags":["semaglutide","drug-delivery-systems","oral-peptide-delivery","pharmacokinetics"],"studyType":"laboratory study (pharmaceutical formulation)","evidenceStrength":"low (in vitro)","keyFinding":"Reverse micelles loaded semaglutide into self-emulsifying oral delivery systems with 4.2 times more drug than hydrophobic ion pairs, and doubled intestinal cell permeability versus free peptide.","whyItMatters":"Oral delivery of peptide drugs is a major pharmaceutical challenge. These formulation strategies could make oral semaglutide more bioavailable without the current requirement for fasting and specific timing.","specificNumbers":"RM: 4.2x higher payload than HIP; 2x higher lipophilicity; droplet sizes 50-300 nm; PDI ~0.3; at least 2-fold permeability increase across Caco-2; cell survival >75% at 0.1%","methodology":"Reverse micelle and HIP formation with semaglutide. SEDDS preparation and characterization (size, zeta, cytocompatibility). Caco-2 permeability studies. Hemolysis testing.","limitations":"In vitro only. Caco-2 monolayer is a simplified model of the intestine. In vivo absorption may be very different. Stability during storage and in gastric acid not assessed."},{"rthcId":"RPEP-13407","title":"Pilot-Scale Production of Sericin-Derived Oligopeptides (SDOs) from Yellow Silk Cocoons: Peptide Characterization and Specifications.","authors":"Sangsawad, Papungkorn; Chumee, Surangkhanang; Laosam, Phanthipha; Roytrakul, Sittiruk; Katemala, Sasikan; Sutheerawattananonda, Manote","year":2025,"journal":"Foods (Basel, Switzerland), 14(3)","doi":"10.3390/foods14030500","pmid":"39942094","tags":["bioactive-peptides","food-derived-peptides","blood-pressure","type-2-diabetes"],"studyType":"laboratory study (food science)","evidenceStrength":"low (in vitro)","keyFinding":"Silk cocoon-derived oligopeptides produced at pilot scale (300L) showed DPP-IV and ACE inhibitory activity, with stability maintained for 6 months across storage temperatures.","whyItMatters":"Scaling up bioactive peptide production from lab to pilot without losing activity is a key step toward functional food ingredients that could help manage blood sugar and blood pressure.","specificNumbers":"300L batch: DH 8.63%, solid recovery 94.35%; peptides <1000 Da; DPP-IV IC50 >1.35 mM; ACE IC50 18.10 microM; stable 6 months at 4/25/45C; meets food safety MRLs","methodology":"Pilot-scale (25L and 300L) enzymatic hydrolysis of sericin from yellow silk cocoons using Neutrase. Ultrafiltration. DPP-IV and ACE inhibition assays. Peptide characterization. Stability and safety testing.","limitations":"In vitro enzyme inhibition only. No human efficacy data. IC50 values may not translate to meaningful effects when consumed as food. Single enzyme (Neutrase) used."},{"rthcId":"RPEP-13408","title":"Exploiting peptide chirality and transport to dissect the complex mechanism of action of host peptides on bacteria.","authors":"Sankari, Siva; Arnold, Markus F F; Babu, Vignesh M P; Deutsch, Michael; Walker, Graham C","year":2025,"journal":"PLoS genetics, 21(12), e1011892","doi":"10.1371/journal.pgen.1011892","pmid":"41379853","tags":["antimicrobial-peptides","peptide-drug-design","membrane-interactions"],"studyType":"laboratory study (microbiology)","evidenceStrength":"low (in vitro with genetic tools)","keyFinding":"By using mirror-image peptide forms and a bacterial transporter mutant, researchers separated three distinct mechanisms of the plant peptide NCR247: membrane disruption, heme sequestration in the cytoplasm, and stereospecific signaling in the periplasm.","whyItMatters":"Antimicrobial peptides often do many things at once. This study shows how to untangle their separate mechanisms, which is essential for designing better peptide drugs.","specificNumbers":"L- and D-NCR247 compared; BacA transporter mutant strain; 3 mechanisms separated: membrane disruption (chirality-independent), heme sequestration (chirality-independent, BacA-dependent), two-component signaling (L-only, periplasmic)","methodology":"L- and D-enantiomers of NCR247 tested on wild-type and BacA-deficient S. meliloti. Membrane permeabilization, heme binding, iron starvation, and two-component system activation assessed.","limitations":"Specific to NCR247 and S. meliloti. BacA transporter is not found in all bacteria. Results may not generalize to all AMPs. In vitro bacterial work only."},{"rthcId":"RPEP-13409","title":"Long-term efficacy of daily oral semaglutide as add-on or switch therapy in adults with type 2 diabetes: a 12-month real-world retrospective study.","authors":"Sansone, Daniela; Garino, Francesca; Gottero, Cristina; Gauna, Carlotta; Clerico, Alessandra; Corneli, Ginevra; Di Noi, Fabiana; Mainolfi, Alessandra Rita; Rossi, Claudio; Marafetti, Lisa; Matteoda, Cristina; Balbo, Marcella Libera; Petraroli, Giuliana; Bonelli, Nadia; Toscano, Claudia Chiara M; Visconti, Licia; Oleandri, Salvatore","year":2025,"journal":"Acta diabetologica, 62(9), 1469-1478","doi":"10.1007/s00592-025-02475-6","pmid":"40014091","tags":["glp1-receptor-agonists","semaglutide","type-2-diabetes","oral-peptide-delivery","hba1c"],"studyType":"retrospective observational study","evidenceStrength":"moderate","keyFinding":"Oral semaglutide reduced HbA1c by 0.84% and body weight by 2.28 kg over 12 months in 950 real-world patients with type 2 diabetes. 53% achieved HbA1c under 7%.","whyItMatters":"This is one of the largest real-world studies of oral semaglutide as add-on or switch therapy, confirming effectiveness in typical clinical practice patients who are older and have more comorbidities than trial participants.","specificNumbers":"n=950; mean age 68.3; 63.7% female; -0.84% HbA1c (p<0.001); 53% reached HbA1c <=7%; -2.28 kg weight (p<0.001); significant drops in DBP and LDL (p<0.001); 18.4% achieved dual endpoint","methodology":"Retrospective real-world study. Primary endpoint: HbA1c change at 12 months. Secondary: weight, proportion achieving targets, cardiovascular parameters.","limitations":"Retrospective, no control group. Patients who discontinued not fully tracked. Weight loss (2.28 kg) is modest compared to injectable semaglutide. Dose not specified for most patients."},{"rthcId":"RPEP-13410","title":"Antibacterial Activity and Action Mechanism of Synthetic Interleukin-8 Derived Peptides Against Flavobacterium psychrophilum.","authors":"Santana, Paula A; Tamayo, Laura; Stambuk, Felipe; Aguilar, Luis Felipe; Cortés, Marcos; Guzmán, Fanny; Forero, Juan Carlos; Romero, María Soledad; Álvarez, Claudio A","year":2025,"journal":"Journal of fish diseases, 48(8), e14056","doi":"10.1111/jfd.14056","pmid":"39624862","tags":["antimicrobial-peptides","immune-modulation","aquaculture"],"studyType":"laboratory study","evidenceStrength":"low (in vitro)","keyFinding":"Interleukin-8-derived salmon peptides killed Flavobacterium psychrophilum by binding to and disrupting bacterial membranes, with ssIL-8-alpha showing complete outer membrane detachment at 30 micromolar.","whyItMatters":"Flavobacterium causes major losses in salmon farming. Fish-derived antimicrobial peptides could replace antibiotics in aquaculture, reducing the risk of drug resistance.","specificNumbers":"ssIL-8-alpha: growth inhibition at 30 microM; complete outer membrane detachment in 20 min; omIL-8-alpha: membrane alterations at 15 min at 15-30 microM; both tested against F. psychrophilum","methodology":"Synthetic peptide antibacterial activity assays. Fluorescence microscopy for membrane binding and fluidity. SEM and TEM for membrane ultrastructure. Time-course experiments.","limitations":"In vitro only against a single fish pathogen. Peptide stability in fish tissue or water not tested. Cost of synthetic peptide production for aquaculture not addressed."},{"rthcId":"RPEP-13411","title":"GLP-1 agonists in neurodegeneration: a multimodal biomarker-guided approach.","authors":"Santiago, Jose A; Gutierrez-Silva, Jean C; Hsu, Wei-Chuan; Sanchez, Kameron; Almanza, Cesar; Ramos, William; Haq, Ihtsham Ul; Rundek, Tatjana","year":2025,"journal":"Trends in molecular medicine","doi":"10.1016/j.molmed.2025.12.001","pmid":"41444101","tags":["glp1-receptor-agonists","neuroprotection","biomarkers","neurological-disorders"],"studyType":"narrative review","evidenceStrength":"low (review of field)","keyFinding":"Blood-based biomarkers tied to insulin signaling, neurodegeneration, and cardiometabolic dysfunction could guide patient selection and track GLP-1 drug effects in Alzheimers and Parkinsons trials.","whyItMatters":"GLP-1 drugs show promise for brain diseases but clinical trials have had mixed results. Better biomarkers could identify which patients will benefit and measure whether the drugs are hitting their targets.","specificNumbers":"Agents discussed: exenatide, lixisenatide, liraglutide; biomarker categories: insulin signaling, neurodegeneration, cardiometabolic; integration with AI and digital phenotyping proposed","methodology":"Narrative review of GLP-1 RA mechanisms in neurodegeneration, clinical evidence, and emerging biomarker strategies.","limitations":"Narrative format. Most biomarkers discussed are not yet validated for GLP-1 drug monitoring. Digital phenotyping integration is conceptual. Trial results to date are limited."},{"rthcId":"RPEP-13412","title":"Peptide receptor radionuclide therapy with somatostatin analogs beyond gastroenteropancreatic neuroendocrine tumors.","authors":"Santo, Giulia; di Santo, Gianpaolo; Cicone, Francesco; Virgolini, Irene","year":2025,"journal":"Journal of neuroendocrinology, 37(3), e70013","doi":"10.1111/jne.70013","pmid":"40064181","tags":["somatostatin-analogs","radionuclide-therapy","cancer-immunotherapy"],"studyType":"narrative review","evidenceStrength":"low (review of field)","keyFinding":"PRRT with somatostatin analogs shows disease control rates up to 80% in lung carcinoids, paragangliomas, and meningiomas, but only 177Lu-DOTATATE is approved (for GEP-NETs). Combination and alpha-emitter therapies are emerging.","whyItMatters":"Many cancers beyond gut neuroendocrine tumors express somatostatin receptors. Expanding PRRT approvals could help patients with limited treatment options.","specificNumbers":"177Lu-DOTATATE approved for GEP-NETs; disease control up to 80% in lung carcinoids, paragangliomas, meningiomas; SST discovered 1972; 5 SSTR subtypes; combination and alpha-emitter therapies emerging","methodology":"Narrative review of PRRT applications beyond GEP-NETs, covering efficacy data from retrospective studies, emerging combination strategies, and alpha-emitter therapy.","limitations":"Narrative format. Most evidence is from small retrospective studies. No randomized trials for non-GEP-NET indications. Patient selection criteria not standardized across tumor types."},{"rthcId":"RPEP-13413","title":"Impact of Salmonella enteritidis Infection and Mechanical Stress on Antimicrobial Peptide Expression in Hermetia illucens.","authors":"Santori, Davide; Fausto, Anna Maria; Gelli, Alessio; Pifferi, Anna Rita; Dottarelli, Samuele; Cucci, Sofia; Di Donato, Francesca; Grifoni, Goffredo; Sezzi, Erminia","year":2025,"journal":"Insects, 16(7)","doi":"10.3390/insects16070692","pmid":"40725322","tags":["antimicrobial-peptides","innate-immunity","infectious-disease"],"studyType":"laboratory study","evidenceStrength":"low (in vitro/animal)","keyFinding":"Black soldier fly larvae upregulated defensin and cecropin expression after Salmonella infection, and even mechanical stress alone triggered antimicrobial peptide production with activity against Salmonella species.","whyItMatters":"Insect-derived antimicrobial peptides could become alternatives to conventional antibiotics. Understanding what triggers their production helps optimize extraction for potential applications.","specificNumbers":"Three time points (T0, T1=4h, T2=24h); antimicrobial action against S. enteritidis (stronger) and S. typhimurium; direct infection produced strongest defensin/cecropin expression","methodology":"Salmonella infection (direct and indirect) and mechanical puncture of H. illucens larvae. Defensin and cecropin expression by molecular testing at three time points. Hemolymph peptide fraction tested by antibiogram and MIC.","limitations":"Insect immune system differs fundamentally from mammalian systems. Crude hemolymph fraction, not purified peptides. Small-scale laboratory study."},{"rthcId":"RPEP-13414","title":"MicroRNAs modulated by DPP-4 inhibitor and bedtime NPH insulin therapy in individuals with type 2 diabetes.","authors":"Santos, Aritania Sousa; Bando, Silvia Yumi; Correa Giannella, Maria Lucia Cardillo; da Silva, Maria Elizabeth Rossi","year":2025,"journal":"Frontiers in endocrinology, 16, 1706951","doi":"10.3389/fendo.2025.1706951","pmid":"41282288","tags":["dpp4-inhibitors","type-2-diabetes","biomarkers","epigenetics","glp1-receptor-agonists"],"studyType":"randomized controlled trial","evidenceStrength":"moderate","keyFinding":"Sitagliptin upregulated 6 miRNAs and NPH insulin upregulated 4 miRNAs in type 2 diabetes patients. Both shared miR-92a-3p and miR-30c-5p. Sitagliptin influenced a broader spectrum suggesting pleiotropic effects beyond glucose control.","whyItMatters":"MicroRNAs may explain how diabetes drugs affect insulin signaling, inflammation, and cell aging beyond just lowering blood sugar.","specificNumbers":"n=32 (16 per group); 6-month treatment; sitagliptin: 6 miRNAs upregulated; NPH insulin: 4 miRNAs upregulated; 2 shared (miR-92a-3p, miR-30c-5p); pathways: insulin signaling, senescence, lipid/atherosclerosis","methodology":"Randomized parallel-group trial. Fasting and postprandial glucose, C-peptide, GLP-1, triglycerides, HbA1c measured. Serum miRNA expression by qPCR. KEGG pathway analysis.","limitations":"Very small sample (n=32). No placebo group. miRNA changes may not translate to clinical outcomes. Short duration. Pathway analysis is hypothesis-generating."},{"rthcId":"RPEP-13415","title":"Phospholipases A2 (PLA2s) and Related Peptides from Bothrops Snake Venoms: History, Structure, Pharmacology, and Inhibitors.","authors":"Santos, Isabela C Dos; Romanazzi, Marcela; Malachias-Pires, Geovanna M; Aragão, Ariani R; Filardi, Eloise T M; Melo-Dos-Santos, Guilherme; Salvador, Lara C; Cerveja, Marcos F; Rocha, Anderson M; Magalhães, Ananda; de Oliveira, Isadora S; Almeida, José R; Santos-Filho, Norival A; Pucca, Manuela B","year":2025,"journal":"Biomolecules, 15(11)","doi":"10.3390/biom15111583","pmid":"41301501","tags":["venom-derived-peptides","antimicrobial-peptides","cancer-immunotherapy"],"studyType":"narrative review","evidenceStrength":"low (review of field)","keyFinding":"Phospholipase A2 enzymes from Bothrops snake venoms cause neurotoxicity, muscle damage, and cell death but also show antiviral and antitumor potential for biotechnological applications.","whyItMatters":"Snake venom components that evolved to harm prey can be repurposed as drugs. PLA2 enzymes are being explored for cancer treatment and antiviral therapy.","specificNumbers":"Multiple PLA2 groups and subgroups; cleave sn-2 position of phospholipids; produce free fatty acids and lysophospholipids; applications: antiviral, antitumor","methodology":"Narrative review of PLA2 enzymes in Bothrops venoms covering structure, classification, pharmacological activities, biotechnological applications, and inhibitors.","limitations":"Narrative format. Many therapeutic applications are at preclinical stage. Snake venom composition varies between species and even individuals."},{"rthcId":"RPEP-13416","title":"Liraglutide improves antioxidant defense in hearts of spontaneously hypertensive female rats independently of changes in blood pressure in a pre-clinical model of menopause.","authors":"Santos, W C Dos; Ronchi, S N; Gonçalves, L A; Oliveira, L C S L; Sousa, G J; Melo Junior, A F; Andrade, T U de; Bissoli, N S; Brasil, G A","year":2025,"journal":"Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas, 58, e14209","doi":"10.1590/1414-431X2025e14209","pmid":"40243818","tags":["glp1-receptor-agonists","liraglutide","cardiovascular-outcomes","oxidative-stress"],"studyType":"preclinical study (animal model)","evidenceStrength":"low (animal study)","keyFinding":"Liraglutide increased heart antioxidant enzymes (SOD2 and catalase) and reduced visceral fat in ovariectomized hypertensive rats without changing blood pressure, glucose tolerance, or cardiac function.","whyItMatters":"Post-menopausal women face higher cardiovascular risk. If GLP-1 drugs protect the heart through antioxidant mechanisms independent of blood pressure, they may offer hidden benefits in this population.","specificNumbers":"Liraglutide 0.6 then 1.2 mg/kg for 4+4 weeks; increased SOD2 and catalase expression; decreased visceral fat; no change in SBP, GTT, cardiac hemodynamics, or calcium-handling proteins","methodology":"Ovariectomized spontaneously hypertensive rats treated with liraglutide for 8 weeks. Blood pressure, glucose tolerance, cardiac hemodynamics, and western blot for antioxidant and calcium-handling proteins.","limitations":"Rat model of menopause (ovariectomy) may not fully replicate human post-menopause. No functional improvement detected despite biochemical changes. Short duration. Single dose escalation protocol."},{"rthcId":"RPEP-13417","title":"Phase 3 Trial of Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis.","authors":"Sanyal, Arun J; Newsome, Philip N; Kliers, Iris; Østergaard, Laura Harms; Long, Michelle T; Kjær, Mette Skalshøi; Cali, Anna M G; Bugianesi, Elisabetta; Rinella, Mary E; Roden, Michael; Ratziu, Vlad","year":2025,"journal":"The New England journal of medicine, 392(21), 2089-2099","doi":"10.1056/NEJMoa2413258","pmid":"40305708","tags":["glp1-receptor-agonists","semaglutide","liver-disease","obesity"],"studyType":"phase 3 randomized controlled trial","evidenceStrength":"strong","keyFinding":"Semaglutide 2.4 mg resolved MASH in 62.9% of patients versus 34.3% with placebo, and reduced liver fibrosis in 36.8% versus 22.4%, at the 72-week interim analysis.","whyItMatters":"MASH (fatty liver disease with inflammation and scarring) has no widely approved drug treatment. This landmark NEJM trial positions semaglutide as a potential first-line therapy for a disease affecting millions.","specificNumbers":"n=1,197 (2:1 randomization); MASH resolution: 62.9% vs 34.3% (diff 28.7%, p<0.001); fibrosis reduction: 36.8% vs 22.4% (diff 14.4%, p<0.001); combined: 32.7% vs 16.1% (p<0.001); weight: -10.5% vs -2.0% (p<0.001)","methodology":"Phase 3, multicenter, randomized, double-blind, placebo-controlled trial. Patients with biopsy-confirmed MASH and fibrosis stage 2-3. Weekly SC semaglutide 2.4 mg vs placebo for 240 weeks. Interim analysis at 72 weeks (first 800 patients). Primary endpoints: MASH resolution without fibrosis worsening; fibrosis improvement without MASH worsening.","limitations":"Interim analysis; full trial (240 weeks) still ongoing. GI adverse events common with semaglutide. Pain scores did not improve. Long-term durability and effect on liver-related clinical events unknown."},{"rthcId":"RPEP-13418","title":"Real-World Usage of Once-Daily Oral Semaglutide in Adults with Type 2 Diabetes: Findings from PIONEER REAL India.","authors":"Sanyal, Debmalya; Saboo, Banshi; Phatak, Sanjeev R; Kumar, Prasanna K M; Basu, Debasis; Verma, Nikhil; Nair, Arjun; Bhattacharjee, Kingshuk; Aneja, Pankaj; Makkar, Brij M M; Negalur, Vijay; Mithal, Ambrish; Unnikrishnan, Ambika G","year":2025,"journal":"Indian journal of endocrinology and metabolism, 29(5), 523-530","doi":"10.4103/ijem.ijem_179_25","pmid":"41229720","tags":["glp1-receptor-agonists","semaglutide","type-2-diabetes","oral-peptide-delivery","hba1c"],"studyType":"prospective observational study","evidenceStrength":"moderate","keyFinding":"Oral semaglutide reduced HbA1c by 1.78 percentage points and body weight by 4.5 kg in Indian patients with type 2 diabetes over 34-44 weeks, with greater reductions in those with higher baseline HbA1c.","whyItMatters":"India has the second-largest diabetes population worldwide. This study confirms oral semaglutide works well in Indian patients, who often present with higher baseline HbA1c than Western populations.","specificNumbers":"n=388; mean age 50.1; baseline HbA1c 9.0%, weight 89.0 kg; -1.78% HbA1c (p<0.001); -4.5 kg weight; baseline >9% subgroup: -2.55% HbA1c; 70.1% completion rate","methodology":"Multicenter, non-interventional, 34-44 week prospective study. On-treatment analysis. Primary: HbA1c change. Secondary: weight, HbA1c target achievement, combined endpoints.","limitations":"Observational single-arm study without control group. 30% did not complete. On-treatment analysis excludes dropouts. Indian-specific results may not generalize to all populations."},{"rthcId":"RPEP-13419","title":"Mito-phytosomal nanocarriers of purslane extract augments apoptosis in A549 cells.","authors":"Sardarabadi, Hadi; Zarei, Seyed Mohammad; Dolati, Masoumeh; Darvishi, Mohammad Hasan; Tavakolizadeh, Mahdi; Zohrab, Fatemeh; Javadi, Hamidreza","year":2025,"journal":"Journal of liposome research, 35(4), 455-468","doi":"10.1080/08982104.2025.2521718","pmid":"40574601","tags":["peptide-drug-design","drug-delivery-systems","cancer-immunotherapy","nanotechnology"],"studyType":"preclinical study (in vitro)","evidenceStrength":"low (cell culture)","keyFinding":"Mitochondria-targeted phytosomes using an SS peptide delivered purslane extract to lung cancer cells, inducing 69.6% apoptosis while sparing normal fibroblasts.","whyItMatters":"Targeting mitochondria directly with peptide-functionalized nanocarriers could make plant-based anti-cancer compounds more effective against hard-to-treat lung cancers.","specificNumbers":"Size 112.2 nm; PDI 0.26; zeta -30.67 mV; 97% encapsulation; 12.19% loading; 69.6% apoptosis in A549; no significant HFF toxicity","methodology":"Phytosome preparation with SS peptide via DSPE-PEG-maleimide crosslinker. DLS, SEM characterization. HPLC for quercetin/apigenin quantification. Cytotoxicity in A549 and HFF cells. Drug release profiling.","limitations":"In vitro only with two cell lines. Single cancer type tested. No in vivo data. Plant extract composition is complex and may vary between batches."},{"rthcId":"RPEP-13420","title":"Effects of combination therapy with SGLT2 inhibitors and GLP-1 receptor agonists on CRT response and clinical outcomes in in type 2 diabetes mellitus patients receiving chronic anti-diabetic medications: A multicenter observational study.","authors":"Sardu, Celestino; Marfella, Ludovica Vittoria; Rinaldi, Luca; Sasso, Ferdinando Carlo; Cozzolino, Domenico; Nappo, Francesco; Sellitto, Ausilia; Romano, Ciro; Carusone, Caterina; D'Onofrio, Nunzia; Trotta, Maria Consiglia; Riccio, Joshua; Cioffi, Domenico; Volpicelli, Mario; Marca, Carmine La; Marrazzo, Natale; Giordano, Valerio; Fumagalli, Carlo; Landolfi, Alessandro; Abitabile, Marianna; Marfella, Lorenza; Balestrieri, Maria Luisa; Marfella, Raffaele","year":2025,"journal":"Diabetes research and clinical practice, 228, 112452","doi":"10.1016/j.diabres.2025.112452","pmid":"40912462","tags":["glp1-receptor-agonists","sglt2-inhibitors","cardiovascular-outcomes","type-2-diabetes"],"studyType":"prospective multicenter observational study","evidenceStrength":"moderate","keyFinding":"Combining GLP-1 RAs with SGLT2 inhibitors in diabetic patients with cardiac resynchronization devices improved CRT response (66.3% vs ~59%) and reduced heart failure hospitalizations (15.7% vs ~24%) versus either drug alone.","whyItMatters":"Diabetic patients with heart failure often respond poorly to cardiac devices. Adding both drug classes together may significantly improve outcomes beyond what either drug achieves alone.","specificNumbers":"n=2,257 (SGLT2i: 874, GLP-1 RA: 808, combo: 575); CRT response: 66.3% combo vs 59.6% SGLT2i vs 59.2% GLP-1 RA (p=0.014); HF hospitalization: 15.7% vs 23.5% vs 24.4% (p=0.001); combo HR 1.659 for CRT response, HR 0.822 for HF hospitalization","methodology":"Prospective multicenter observational study. Three groups by diabetes medication. Primary endpoints: CRT response and HF hospitalizations at 1 year. Multivariate Cox regression.","limitations":"Observational design with potential selection bias. Patients on combination therapy may have different baseline characteristics. No randomization. One-year follow-up may be too short for device outcomes."},{"rthcId":"RPEP-13421","title":"Effects of SGLT2i therapy on cardiac electrophysiological properties and arrhythmias in diabetic patients with implantable cardiac defibrillator.","authors":"Sardu, Celestino; Trotta, Maria Consiglia; Marfella, Ludovica Vittoria; D'Amico, Giovambattista; La Marca, Carmine; Mauro, Ciro; Santamaria, Matteo; Giordano, Valerio; Turriziani, Fabrizio; Rafaniello, Concetta; Sasso, Ferdinando Carlo; Calabro, Paolo; Pizzi, Carmine; Marfella, Raffaele; Capuano, Annalisa; Paolisso, Giuseppe","year":2025,"journal":"Pharmacological research, 216, 107759","doi":"10.1016/j.phrs.2025.107759","pmid":"40328387","tags":["sglt2-inhibitors","cardiovascular-outcomes","biomarkers","type-2-diabetes"],"studyType":"prospective observational study","evidenceStrength":"moderate","keyFinding":"SGLT2 inhibitors improved cardiac electrophysiology, reduced ventricular tachycardia (10.8% vs 17.4%), inappropriate shocks, heart failure hospitalizations, and cardiac deaths in diabetic ICD/CRT patients over 1 year.","whyItMatters":"Dangerous heart rhythms are a leading cause of death in patients with implanted defibrillators. SGLT2 inhibitors may protect against these arrhythmias by reducing inflammation and sympathetic tone.","specificNumbers":"334 SGLT2i vs 794 non-users; VT: 10.8% vs 17.4%; inappropriate shocks: 9.6% vs 14.9%; HF hospitalization: 15.0% vs 27.2%; cardiac death: 3.0% vs 6.7%; all p<0.05; SGLT2i HR 0.592 for VT, HR 0.497 for HF hosp, HR 0.677 for cardiac death","methodology":"Prospective observational study of diabetic ICD/CRT patients. 1-year follow-up. Device lead parameters, arrhythmia events, HF hospitalizations, cardiac deaths. Inflammatory and neurohumoral markers. Multivariate Cox regression.","limitations":"Observational with potential selection bias. SGLT2i users may have been healthier at baseline. Not randomized. Multiple endpoints increase type I error risk."},{"rthcId":"RPEP-13422","title":"GLP-1 Receptor Agonists Are Associated with Reduced Ascending Aorta Dilatation in Patients with Type 2 Diabetes: A Prospective Study.","authors":"Sardu, Celestino; Marfella, Ludovica Vittoria; Fumagalli, Carlo; Rinaldi, Luca; Sasso, Ferdinando Carlo; Cozzolino, Domenico; Nappo, Francesco; Sellitto, Ausilia; Romano, Ciro; Carusone, Caterina; Russo, Pasquale; Marfella, Lorenza; Tarantino, Nicola Maria; Carpinella, Gerardo; Furbatto, Fulvio; Gentile, Sandro; Guarino, Giuseppina; Satta, Ersilia; Bellis, Alessandro; Marinelli, Luca; Donisi, Isabella; D'Onofrio, Nunzia; Mauro, Ciro; Cappabianca, Salvatore; Balestrieri, Maria Luisa; Marfella, Raffaele","year":2025,"journal":"International journal of molecular sciences, 26(20)","doi":"10.3390/ijms26209977","pmid":"41155271","tags":["glp1-receptor-agonists","cardiovascular-outcomes","type-2-diabetes","inflammation"],"studyType":"prospective observational study","evidenceStrength":"moderate","keyFinding":"GLP-1 RA therapy slowed ascending aorta dilation by two-thirds over 2 years in patients with type 2 diabetes (+0.36 mm vs +1.05 mm in controls), with reduced MMP-9 and CRP levels.","whyItMatters":"Aortic dilation can lead to dissection or rupture. If GLP-1 drugs slow this progression, they may provide a new non-surgical strategy for managing subclinical aortic disease in diabetics.","specificNumbers":"n=127 (57 GLP-1 RA, 70 controls); aortic diameter change: +0.36 vs +1.05 mm (p<0.05); decreased MMP-9 and CRP (p<0.05); independent predictor in multivariate models","methodology":"Prospective observational study. CT angiography for ascending aortic diameter at baseline and 24 months. Circulating MMP-9, TIMP-1, CRP, and osteoprotegerin measured. Multivariate regression.","limitations":"Observational, not randomized. Small sample. Selection bias possible. 2-year follow-up may be too short for aortic events. Subclinical dilation may not progress to clinical disease in all patients."},{"rthcId":"RPEP-13423","title":"GLP-1 receptor agonists in obesity treatment: Effects on cardiometabolic variables and cardiovascular disease.","authors":"Sardà, Helena; Genua, Idoia; Miñambres, Inka","year":2025,"journal":"Medicina clinica, 165(1), 106951","doi":"10.1016/j.medcli.2025.106951","pmid":"40378625","tags":["glp1-receptor-agonists","semaglutide","tirzepatide","liraglutide","cardiovascular-outcomes"],"studyType":"narrative review","evidenceStrength":"low (review of field)","keyFinding":"GLP-1 RA drugs improve weight, glucose metabolism, blood pressure, lipids, and fatty liver disease. Semaglutide 2.4 mg reduces cardiovascular death, MI, and stroke; tirzepatide reduces cardiovascular death and heart failure symptoms.","whyItMatters":"This review synthesizes the full cardiometabolic impact of GLP-1 drugs approved for obesity, showing they are far more than weight loss drugs.","specificNumbers":"Semaglutide 2.4 mg: reduced CV mortality, nonfatal MI, stroke; tirzepatide: reduced CV mortality, HF symptoms in obesity+HF; improvements in TG, HDL, BP, MASLD across drug class","methodology":"Narrative review of cardiovascular and metabolic outcomes from clinical trials of liraglutide, semaglutide, and tirzepatide in obesity.","limitations":"Narrative format. Some outcomes are from specific subpopulations. Long-term cardiovascular data are still accumulating for newer agents."},{"rthcId":"RPEP-13424","title":"Shaping Antitumor Immunity with Peptide Vaccines: Implications of Immune Modulation at the Vaccine Site.","authors":"Sarkar, Amrita; Rabinovich, Emily Pauline; Slingluff, Craig Lee","year":2025,"journal":"Vaccines, 13(11)","doi":"10.3390/vaccines13111150","pmid":"41295524","tags":["vaccine-development","cancer-immunotherapy","peptide-drug-design","immune-modulation"],"studyType":"narrative review","evidenceStrength":"low (review of field)","keyFinding":"The vaccine site microenvironment (VSME) affects how peptide cancer vaccines generate immune responses. Repeated vaccination at the same site may improve antigen presentation, but immune cell sequestration at the injection site could limit systemic efficacy.","whyItMatters":"Most vaccine trials only measure blood immune responses. Understanding what happens at the injection site could explain why some vaccines fail and how to improve them.","specificNumbers":"Multiple platforms reviewed: protein, peptide, DNA, RNA, cell-based vaccines; VSME assessment varies in sampling, timing, and analyses across studies","methodology":"Narrative review of vaccine site microenvironment studies in cancer peptide vaccination, covering adjuvant effects, local immune dynamics, and correlations with systemic immunity.","limitations":"Narrative format. Highly variable methodologies across reviewed studies limit comparability. No standardized VSME assessment protocol exists. Most data from small phase I/II trials."},{"rthcId":"RPEP-13425","title":"RNA toehold switch-based reporter assay to assess bacterial uptake of antisense oligomers.","authors":"Sarkar, Paramita; Popella, Linda; Pérez-Jiménez, Sandra; Vogel, Jörg","year":2025,"journal":"mBio, 16(4), e0398324","doi":"10.1128/mbio.03983-24","pmid":"40035593","tags":["cell-penetrating-peptides","antimicrobial-peptides","drug-delivery-systems","antimicrobial-resistance"],"studyType":"laboratory study (tool development)","evidenceStrength":"low (in vitro proof of concept)","keyFinding":"A new reporter assay using RNA toehold switches detected up to 60-fold activation when cell-penetrating peptides delivered antisense oligomers into bacteria, enabling high-throughput screening of delivery carriers.","whyItMatters":"Getting antisense drugs into bacteria is a major bottleneck for developing precision antibiotics. This assay could dramatically speed up the search for effective delivery peptides.","specificNumbers":"Up to 60-fold reporter activation; tested in E. coli and S. enterica; SbmA-dependent uptake confirmed; PNA-based antisense oligomers; high dynamic range and sensitivity","methodology":"RNA toehold switch fused to fluorescent reporter in bacteria. Activation by PNA antisense oligomer delivered via different CPPs. Fluorescence quantification. BacA/SbmA transporter mutant studies.","limitations":"In vitro bacterial system. Reporter activation may not directly correlate with gene silencing. Limited to two bacterial species. CPP performance may differ in infection models."},{"rthcId":"RPEP-13426","title":"Unraveling the role of CGRP in neurological diseases: a comprehensive exploration to pathological mechanisms and therapeutic implications.","authors":"Sarkar, Sampriti; Porel, Pratyush; Kosey, Sourabh; Aran, Khadga Raj","year":2025,"journal":"Molecular biology reports, 52(1), 436","doi":"10.1007/s11033-025-10542-y","pmid":"40299101","tags":["cgrp","neuropeptides","neuroprotection","neurological-disorders"],"studyType":"narrative review","evidenceStrength":"low (review of field)","keyFinding":"CGRP plays a dual role in neurodegenerative diseases: it protects neurons by reducing inflammation and promoting survival, but overexpression can cause oxidative stress and excitotoxicity.","whyItMatters":"CGRP-targeting drugs are widely used for migraine. Understanding CGRPs role in Alzheimers, Parkinsons, and ALS could reveal whether these drugs help or harm patients with both conditions.","specificNumbers":"CGRP roles reviewed in AD, PD, HD, MS, ALS, and SMA; both neuroprotective (anti-inflammatory, vasodilation, neuronal survival) and neurotoxic (oxidative stress, excitotoxicity) effects documented","methodology":"Narrative review of CGRP biology in neurodegenerative diseases covering molecular pathways, preclinical and clinical evidence, and therapeutic implications.","limitations":"Narrative format. Most evidence from animal models and cell studies. Context-dependent effects make clinical translation complex. Migraine drug safety in NDD populations not directly studied."},{"rthcId":"RPEP-13427","title":"Computational cyclic peptide design machine learning & Rosetta based methods.","authors":"Sarmeili, Faraz; Siegler, Hannah; Powers, Andrew C; Hosseinzadeh, Parisa","year":2025,"journal":"Methods in enzymology, 723, 455-476","doi":"10.1016/bs.mie.2025.09.016","pmid":"41266039","tags":["peptide-drug-design","structure-activity-relationships","artificial-intelligence"],"studyType":"methodology review","evidenceStrength":"low (review of computational methods)","keyFinding":"Machine learning and Rosetta-based computational methods can now design cyclic peptides that target flat protein surfaces considered undruggable by small molecules.","whyItMatters":"Cyclic peptides bridge the gap between small drugs and antibodies. Better design tools could accelerate development of drugs for currently untreatable diseases.","specificNumbers":"Macrocyclic peptides target flat/intracellular undruggable surfaces; enhanced proteolytic stability; non-canonical amino acids incorporated; Rosetta and ML-based design methods reviewed","methodology":"Review of computational algorithms including Rosetta-based methods, machine learning approaches, and experimental validation strategies for cyclic peptide design.","limitations":"Methodology review focused on computational approaches. Many designed peptides still need experimental validation. Computational predictions do not always match in vitro activity."},{"rthcId":"RPEP-13428","title":"The effect of GLP-1 receptor agonists on renal outcomes: a systematic review and meta-analysis.","authors":"Sasaki, Takaya; Giang, Samantha M; Wu, Jiajia; Yokoo, Takashi; Gallagher, Martin; Bellomo, Rinaldo; Wang, Amanda Ying","year":2025,"journal":"Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association","doi":"10.1093/ndt/gfaf193","pmid":"40982219","tags":["glp1-receptor-agonists","kidney-disease","cardiovascular-outcomes","meta-analysis"],"studyType":"systematic review and meta-analysis","evidenceStrength":"strong","keyFinding":"GLP-1 RAs reduced the composite renal outcome by 19%, microalbuminuria by 24%, and yearly eGFR loss by 0.45 mL/min across 19 trials with nearly 91,000 patients. MACE dropped 15% and all-cause mortality 14%.","whyItMatters":"This is the largest meta-analysis of GLP-1 drugs and kidney outcomes, confirming renal protection alongside cardiovascular benefits across diverse patient populations.","specificNumbers":"19 trials; n=90,882; mean age 60.8; mean follow-up 25.9 mo; composite renal RR 0.81 (0.73-0.89); microalbuminuria RR 0.76 (0.71-0.82); eGFR loss -0.45 mL/min/yr; MACE RR 0.85 (0.81-0.90); mortality RR 0.86 (0.82-0.91); weight -5.24 kg; HbA1c -0.61%","methodology":"Systematic review searching Medline, EMBASE, Cochrane to December 2024. Random-effects meta-analysis of RCTs. Primary: composite renal outcome. Subgroups by diabetes status, CKD, and individual drugs.","limitations":"Most trials enrolled diabetes patients; limited data without diabetes. Progression to kidney failure not significantly reduced. Heterogeneous definitions of renal outcomes across trials. GI side effects common."},{"rthcId":"RPEP-13429","title":"Molecular docking and dynamics simulation of antimicrobial peptides against adhesion proteins of peri-implant pathogens.","authors":"Sasany, Rafat; Alizadeh, Ahmed; Mosaddad, Seyed Ali; Diaz, Pedro","year":2025,"journal":"Scientific reports, 15(1), 41046","doi":"10.1038/s41598-025-24925-5","pmid":"41266710","tags":["antimicrobial-peptides","ll-37-cathelicidin","dental-applications","biofilm"],"studyType":"computational study","evidenceStrength":"low (in silico only)","keyFinding":"LL-37 and Tachystatin A2 showed strong, stable binding to bacterial adhesion proteins FimA and BspA in molecular dynamics simulations, suggesting potential for anti-biofilm dental implant coatings.","whyItMatters":"Peri-implantitis causes late dental implant failure. Coating implants with antimicrobial peptides that block bacterial attachment could prevent biofilm formation.","specificNumbers":"100 ns MD simulations; MM-PBSA binding energy calculations; FimA and BspA target proteins; P. gingivalis, T. forsythia, T. denticola pathogens; LL-37 and Tachystatin A2 showed strongest binding","methodology":"Homology modeling for protein structures. AutoDock Vina docking. 100 ns GROMACS molecular dynamics. RMSD, hydrogen bond analysis, and MM-PBSA binding energy evaluation.","limitations":"Entirely computational. No experimental validation of anti-adhesion activity. Static protein models may not capture dynamic bacterial surface conditions. In vivo biofilm formation is more complex."},{"rthcId":"RPEP-13430","title":"Functional roles of purified yapsins from Candida glabrata (Nakaseomyces glabratus) in immune modulation and cross-species biofilm formation.","authors":"Satala, Dorota; Satala, Grzegorz; Kulig, Kamila; Karkowska-Kuleta, Justyna; Kozik, Andrzej; Rapala-Kozik, Maria","year":2025,"journal":"Scientific reports, 15(1), 32115","doi":"10.1038/s41598-025-15577-6","pmid":"40890180","tags":["antimicrobial-peptides","infection-immunity"],"studyType":"laboratory study","evidenceStrength":"preliminary","keyFinding":"Two fungal proteins (Yps3 and Yps9) from Candida glabrata broke down human antimicrobial peptides like LL-37, histatin 5, and NAT26. In a wax moth model, pre-treatment with these proteins boosted larval survival and immune activity.","whyItMatters":"These findings show how a drug-resistant yeast disarms the body's natural peptide defenses. Understanding this may help researchers develop new treatments for hard-to-treat fungal infections.","specificNumbers":"Both proteins worked best at pH 5.5-7.0. They resisted pepstatin A, a common protease blocker. Yps9 promoted biofilm dispersal in a related species.","methodology":"Researchers purified Yps3 and Yps9 from Candida glabrata cultures. They tested protease activity, peptide degradation, and biofilm effects in the lab. They used a Galleria mellonella (wax moth larvae) infection model for immune studies.","limitations":"Insect model only. No human or mammalian data. Purified proteins may behave differently than they do on living fungal cells."},{"rthcId":"RPEP-13431","title":"An Online Prescription for Hospitalisation: Euglycaemic Ketoacidosis Caused by an Online Tirzepatide Prescription.","authors":"Sathambihai, Thibagaran; Mathur, Kushagra; Siddavaram, Seshnag","year":2025,"journal":"Cureus, 17(11), e97410","doi":"10.7759/cureus.97410","pmid":"41431533","tags":["glp1-receptor-agonists","weight-management","safety-tolerability"],"studyType":"case report","evidenceStrength":"low","keyFinding":"A 61-year-old woman with no diabetes developed euglycemic ketoacidosis after six weeks on tirzepatide prescribed online for weight loss. Blood sugar was normal, but she had significant ketones and metabolic acidosis.","whyItMatters":"This case highlights a serious but under-recognized side effect of tirzepatide. Online prescribing with less monitoring may increase the risk of missing early warning signs.","specificNumbers":"61-year-old woman. No past medical history. Developed euglycemic ketoacidosis after 6 weeks of tirzepatide (Mounjaro) therapy.","methodology":"Single case report with clinical documentation of the adverse event and treatment course.","limitations":"Single case. Cannot determine how common this side effect is from one report. No control or comparison group."},{"rthcId":"RPEP-13432","title":"Biomimetic Nanomicelles: Utilizing Peptide Transporters to Overcome Corneal Barrier for Treating Fungal Infection.","authors":"Sathe, Priyadarshini; Nagarjuna, Vasagiri; Sharma, Hanuman; Velpandian, Thirumurthy; Garg, Prashant; Nirmal, Jayabalan","year":2025,"journal":"Molecular pharmaceutics, 22(11), 6575-6587","doi":"10.1021/acs.molpharmaceut.5c00423","pmid":"41115049","tags":["drug-delivery-systems","antimicrobial-peptides"],"studyType":"laboratory study","evidenceStrength":"preliminary","keyFinding":"Nanomicelles designed to target peptide transporters on the cornea delivered natamycin into the eye far more effectively. The formulation matched antifungal activity of the standard eye drop at one-third the dosing frequency.","whyItMatters":"Less than 5% of eye drop drugs reach deep corneal tissue. This delivery system could reduce dosing from 12 times to 4 times daily for fungal eye infections, improving patient compliance.","specificNumbers":"0.6% natamycin loaded in nanomicelles. Comparable antifungal activity at 4 times daily vs. 12 times daily for marketed 5% natamycin suspension. Less than 5% of standard eye drops reach target tissue.","methodology":"Researchers conjugated a peptide transporter ligand (Gly-Sar) to TPGS polymer to form nanomicelles. They tested corneal permeation ex vivo and in vivo, and antifungal activity against Candida albicans and Aspergillus flavus.","limitations":"Animal and lab study only. No human clinical data. Long-term safety of the nanomicelle system is unknown."},{"rthcId":"RPEP-13433","title":"Insights into GLP-1 and insulin secretion mechanisms in pasireotide-induced hyperglycemia highlight effectiveness of Gs-targeting diabetes treatment.","authors":"Sato, Junichiro; Manaka, Katsunori; Horikoshi, Hirofumi; Taguchi, Maho; Harada, Kazuki; Tsuboi, Takashi; Nangaku, Masaomi; Iiri, Taroh; Makita, Noriko","year":2025,"journal":"Scientific reports, 15(1), 9494","doi":"10.1038/s41598-025-90896-2","pmid":"40108209","tags":["glp1-receptor-agonists","metabolic-disorders","hormones-endocrine"],"studyType":"laboratory study (with case report)","evidenceStrength":"preliminary","keyFinding":"Pasireotide caused severe blood sugar problems mainly by shutting down GLP-1 secretion. A GLP-1 analog worked better than a DPP-4 inhibitor to restore insulin release in both a patient and cell models.","whyItMatters":"Pasireotide treats acromegaly but often causes hard-to-manage high blood sugar. This study clarifies why and suggests GLP-1 analogs as the better treatment choice.","specificNumbers":"One patient with acromegaly switched from DPP-4 inhibitor to GLP-1 analog. In vitro: pasireotide blocked GLP-1 secretion via SSTR5-Gi pathway. GLP-1 partially restored insulin secretion in GLP-1R-MIN-6 cells.","methodology":"Clinical case of drug switching plus in vitro experiments using MIN-6 beta cells stably expressing GLP-1R and GLUTag intestinal L-cells. Tested interactions between glucose, Gs-coupled receptor stimulation, and pasireotide.","limitations":"Single patient case. Cell line results may not fully reflect human physiology. No controlled clinical trial."},{"rthcId":"RPEP-13434","title":"Adding Semaglutide to SGLT2 Inhibitors Reduces Liver Enzymes in Patients with Type 2 Diabetes Complicated by Metabolic Dysfunction Associated Steatotic Liver Disease: A Retrospective Observational Study.","authors":"Sato, Kanako; Irie, Yoko; Asai, Hiroaki; Yoshioka, Saori; Murakawa, Keisuke; Sho, Hiroyuki; Inui, Ryoko; Kosugi, Motohiro; Hazama, Yoji; Yasuda, Tetsuyuki","year":2025,"journal":"Internal medicine (Tokyo, Japan)","doi":"10.2169/internalmedicine.6239-25","pmid":"41062312","tags":["glp1-receptor-agonists","metabolic-disorders","liver-gi"],"studyType":"retrospective observational study","evidenceStrength":"low-moderate","keyFinding":"Adding semaglutide to ongoing SGLT2 inhibitor therapy for 6 months lowered liver enzymes (AST, ALT, gamma-GTP) in patients with type 2 diabetes and fatty liver disease. Liver fibrosis markers did not improve.","whyItMatters":"Many people with type 2 diabetes also have fatty liver disease. This suggests semaglutide may provide added liver benefits on top of SGLT2 inhibitors, though fibrosis improvement was not seen.","specificNumbers":"47 patients. Body weight dropped from 80.9 kg to 77.3 kg. HbA1c fell from 7.4% to 6.9%. AST dropped from 30.4 to 26.3 U/L (p=0.014). ALT dropped from 42.4 to 35.7 U/L (p=0.022). Gamma-GTP dropped from 46.5 to 38.0 U/L (p=0.001). Fibrosis-4 index did not improve.","methodology":"Retrospective review of 47 patients with T2DM and MASLD on SGLT2 inhibitors for at least 12 months. Compared liver markers at baseline vs. 6 months after adding semaglutide.","limitations":"Retrospective design with no control group. Small sample. Cannot separate semaglutide's liver effects from weight loss effects. No imaging data for liver fat."},{"rthcId":"RPEP-13435","title":"ROR1 as an Immunotherapeutic Target for Inducing Antitumor Helper T Cell Responses Against Head and Neck Squamous Cell Carcinoma.","authors":"Sato, Ryosuke; Yamaki, Hidekiyo; Inoue, Takahiro; Sakaue, Shota; Ominato, Hisataka; Wakisaka, Risa; Komatsuda, Hiroki; Kono, Michihisa; Ohara, Kenzo; Kosaka, Akemi; Ohkuri, Takayuki; Nagato, Toshihiro; Kumai, Takumi; Kishibe, Kan; Kobayashi, Hiroya; Takahara, Miki","year":2025,"journal":"Cancers, 17(14)","doi":"10.3390/cancers17142326","pmid":"40723210","tags":["cancer-oncology","immunology-inflammation"],"studyType":"laboratory study","evidenceStrength":"preliminary","keyFinding":"A peptide derived from the ROR1 protein (ROR1403-417) activated helper T cells that killed head and neck cancer cells. Adding immune checkpoint blockers boosted the T cell response further.","whyItMatters":"Head and neck cancer responds poorly to current immunotherapy. ROR1 is overexpressed in 80% of these tumors but barely present in normal tissue, making it a promising vaccine target.","specificNumbers":"ROR1 positivity: 80.0% in HNSCC tissues vs. 16.7% in controls. High ROR1 correlated with advanced clinical stages. Dual PD-L1/PD-L2 blockade enhanced T cell responses.","methodology":"Immunohistochemistry for ROR1 expression. Peptide epitope identification and helper T cell generation. Functional assays for IFN-gamma, granzyme B, and cytotoxicity. Checkpoint inhibitor co-treatment. Peripheral blood T cell screening in HNSCC patients.","limitations":"In vitro study. No clinical trial data. T cell responses in the lab may not reflect tumor killing in living patients."},{"rthcId":"RPEP-13436","title":"A Case of Sarcoidosis Diagnosed Based on Progressive Renal Dysfunction and Lymphadenopathy.","authors":"Sato, Tomohide","year":2025,"journal":"Cureus, 17(5), e83936","doi":"10.7759/cureus.83936","pmid":"40502903","tags":["hormones-endocrine","cardiovascular"],"studyType":"case report","evidenceStrength":"low","keyFinding":"An 89-year-old woman admitted for heart failure was found to have sarcoidosis causing both her heart failure and kidney failure. Persistent lymph node swelling and worsening kidney function despite diuretic treatment prompted the diagnosis.","whyItMatters":"Sarcoidosis can mimic common conditions like heart failure. When kidney function worsens despite effective heart failure treatment, doctors should consider sarcoidosis as the underlying cause.","specificNumbers":"89-year-old woman. BNP 1144.4 pg/mL. Creatinine rose from 2.10 to 5.85 mg/dL by day 14. sIL-2R 3290 U/mL. Serum lysozyme 30.6 mcg/mL. Kidney involvement reported in 6-50% of sarcoidosis cases.","methodology":"Single case report with clinical documentation, imaging, lab work, and lymph node biopsy.","limitations":"Single case. Cannot generalize to all heart failure or sarcoidosis patients. Elderly presentation may not reflect younger populations."},{"rthcId":"RPEP-13437","title":"Computational screening and molecular modeling of probiotic-derived peptides targeting the conserved HR1 domain of SARS-CoV-2 spike protein.","authors":"Sattar, Alireza; Jahromi, Bahar Saadaie; Ghahi, Fatemeh Sadat Jalilzadeh; Hoseini, Golsa Nayeb Ghanbar; Fard, Najaf Allahyari","year":2025,"journal":"Scientific reports, 15(1), 44952","doi":"10.1038/s41598-025-29197-7","pmid":"41461805","tags":["antimicrobial-peptides","drug-delivery-systems"],"studyType":"computational study","evidenceStrength":"preliminary","keyFinding":"Screening 318 probiotic-derived peptides identified plantaricin K as a strong binder to a conserved region of the SARS-CoV-2 spike protein across multiple variants. Simulations showed stable binding and favorable safety profiles.","whyItMatters":"Finding broad-spectrum antivirals that work across SARS-CoV-2 variants is important. This computational work suggests probiotic-derived peptides deserve further lab testing as potential fusion inhibitors.","specificNumbers":"318 bacteriocins screened. Plantaricin K (2KEG) identified as top candidate. Tested against Alpha, Beta, Gamma, Kappa, Epsilon, Omicron, BA.2.86, EG.5.1, HV.1, and JN.1 variants.","methodology":"Sequence conservation analysis (Clustal Omega), protein-peptide docking (HADDOCK 2.4), safety profiling (ToxinPred, AlgPred, HemoPred, others), and molecular dynamics simulations (GROMACS) assessing stability metrics.","limitations":"Computer modeling only. No wet lab experiments, animal studies, or human data. Computational binding predictions often differ from real-world results."},{"rthcId":"RPEP-13438","title":"Tirzepatide and cardiometabolic parameters in obesity: Summary of current evidence.","authors":"Sattar, Naveed; García-Pérez, Luis-Emilio; Rodríguez, Angel; Kapoor, Richa; Stefanski, Adam; Hankosky, Emily R","year":2025,"journal":"Diabetes, obesity & metabolism, 27(10), 5386-5392","doi":"10.1111/dom.16549","pmid":"40555920","tags":["glp1-receptor-agonists","cardiovascular","weight-management"],"studyType":"narrative review","evidenceStrength":"not applicable (review)","keyFinding":"This review summarizes evidence that tirzepatide improves multiple heart and metabolic risk factors beyond blood sugar control, including lipid profiles, blood pressure, kidney markers, liver fat, body composition, and heart failure risk.","whyItMatters":"Tirzepatide's benefits may extend well beyond diabetes and weight loss. Understanding its broad metabolic effects helps clinicians make informed prescribing decisions.","specificNumbers":"Cardiovascular diseases cause roughly one-third of global deaths. Tirzepatide is a once-weekly dual GIP/GLP-1 receptor agonist. Review covers effects on lipids, blood pressure, renal markers, body composition, liver fat, prediabetes progression, and heart failure incidence.","methodology":"Narrative review of published clinical trial evidence on tirzepatide's cardiometabolic effects.","limitations":"Narrative review, not a systematic review or meta-analysis. May not capture all available evidence. Subject to selection bias in study inclusion."},{"rthcId":"RPEP-13439","title":"Tirzepatide and muscle composition changes in people with type 2 diabetes (SURPASS-3 MRI): a post-hoc analysis of a randomised, open-label, parallel-group, phase 3 trial.","authors":"Sattar, Naveed; Neeland, Ian J; Dahlqvist Leinhard, Olof; Fernández Landó, Laura; Bray, Ross; Linge, Jennifer; Rodriguez, Angel","year":2025,"journal":"The lancet. Diabetes & endocrinology, 13(6), 482-493","doi":"10.1016/S2213-8587(25)00027-0","pmid":"40318682","tags":["glp1-receptor-agonists","weight-management","clinical-trials"],"studyType":"post-hoc analysis of randomized controlled trial","evidenceStrength":"moderate","keyFinding":"In the SURPASS-3 MRI substudy, tirzepatide reduced thigh muscle fat infiltration more than expected from weight loss alone. Muscle volume decreased proportionally to weight loss. Compared to insulin degludec, tirzepatide showed distinct muscle composition changes.","whyItMatters":"Weight loss drugs raise concerns about muscle loss. This MRI study suggests tirzepatide's muscle volume changes are typical for the amount of weight lost, and it may actually improve muscle quality by reducing fat within muscle tissue.","specificNumbers":"246 participants analyzed (190 tirzepatide, 56 insulin degludec). Tirzepatide: muscle fat infiltration decreased 0.36 percentage points (p<0.0001). Muscle volume decreased 0.64 L (p<0.0001). Muscle volume Z score decreased 0.22 (p<0.0001). Muscle volume changes matched population-based estimates for weight loss. Fat infiltration reduction exceeded estimates (difference -0.42 pp, p<0.0001).","methodology":"Post-hoc analysis of the SURPASS-3 MRI substudy. Phase 3, randomized, open-label trial comparing tirzepatide (5/10/15 mg weekly) vs. insulin degludec. Thigh MRI at baseline and week 52. Compared observed changes to UK Biobank population estimates (n=2942).","limitations":"Post-hoc exploratory analysis. Open-label design. MRI substudy subset only. Cannot determine if muscle quality improvement translates to functional benefits. Funded by Eli Lilly."},{"rthcId":"RPEP-13440","title":"Clinically relevant infraorbital nerve deflation and chronic constriction injury models of trigeminal neuralgia display unifying mechanisms.","authors":"Satti, Srilakshmi; Ramteke, Shwetali; Chaganti, Sowmya; Padhy, Hara Prasad; Samanthula, Gananadhamu; Dandekar, Manoj P","year":2025,"journal":"Neurochemistry international, 190, 106052","doi":"10.1016/j.neuint.2025.106052","pmid":"40939756","tags":["neuroscience-neurological","pain-management"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"A new rat model of trigeminal neuralgia using nerve deflation showed similar pain behaviors and molecular changes to the existing nerve constriction model. Both models showed elevated CGRP and substance P, altered neurotransmitters, and anxiety/depression-like behaviors.","whyItMatters":"Trigeminal neuralgia causes severe facial pain. This new model more closely mimics the clinical cause (nerve compression) and may improve preclinical drug testing for this condition.","specificNumbers":"Both models showed decreased von Frey threshold (touch sensitivity), elevated CGRP and substance P in trigeminal nucleus/ganglia, altered levels of dopamine, acetylcholine, serotonin, GABA, noradrenaline, and corticosterone across brain regions.","methodology":"Distal infraorbital nerve chronic deflation injury (dIoN CDI) compared to chronic constriction injury (dIoN CCI) in male and female rats. Pain assessed by von Frey filaments, orofacial pain device, grooming time, and grimace scale. Anxiety/depression tests (EPM, SPT, FST, splash test). Molecular analysis of brain, nerve, blood, and fecal samples.","limitations":"Animal study only. Rat models may not fully replicate human trigeminal neuralgia. No drug interventions tested."},{"rthcId":"RPEP-13441","title":"Evaluating Host Defense Peptides: A Comparative Analysis of Synthetic Peptides and Recombinant Concatemers.","authors":"Saubi, Cristina; Carratalá, José Vicente; Bello-Madruga, Roberto; López-Cano, Adrià; Navarro, Susanna; Arís, Anna; Garcia-Fruitós, Elena","year":2025,"journal":"Biomolecules, 15(7)","doi":"10.3390/biom15070980","pmid":"40723852","tags":["antimicrobial-peptides","peptide-manufacturing"],"studyType":"laboratory study","evidenceStrength":"preliminary","keyFinding":"Host defense peptides produced as four-copy chains (tetramers) in bacteria were more antimicrobially active, more structurally stable, and formed nanostructures compared to the same peptides made by chemical synthesis.","whyItMatters":"Antimicrobial peptides could help fight antibiotic resistance, but making them at scale is a major hurdle. This tetramer approach in Lactococcus lactis bacteria could make production cheaper and more effective.","specificNumbers":"Tetrameric (four-copy) peptides produced in Lactococcus lactis. Enhanced antimicrobial activity, structural stability, and nanostructure formation compared to chemically synthesized monomers.","methodology":"Compared host defense peptides produced by chemical synthesis vs. recombinant tetrameric production in Lactococcus lactis. Assessed antimicrobial activity, structural stability, and nanostructure formation.","limitations":"Lab study only. In vitro antimicrobial activity may not translate to in vivo efficacy. Scalability not yet demonstrated at industrial levels."},{"rthcId":"RPEP-13442","title":"Risk management of cardiovascular disease in older patients with diabetes.","authors":"Sawami, Kosuke; Tanaka, Atsushi; Node, Koichi","year":2025,"journal":"Hypertension research : official journal of the Japanese Society of Hypertension, 48(12), 3179-3186","doi":"10.1038/s41440-025-02424-4","pmid":"41102421","tags":["glp1-receptor-agonists","cardiovascular","aging-longevity"],"studyType":"narrative review","evidenceStrength":"not applicable (review)","keyFinding":"This review discusses cardiovascular risk management in older adults with diabetes, focusing on SGLT2 inhibitors and GLP-1 receptor agonists. Both drug classes show consistent efficacy and safety in older patients, but frailty must be considered.","whyItMatters":"Older adults with diabetes face high cardiovascular risk but are often excluded from trials. This review confirms that key newer diabetes drugs remain effective and safe in this vulnerable population.","specificNumbers":"Not specified (review of existing trial evidence in older populations)","methodology":"Mini review of clinical trial evidence on SGLT2 inhibitors and GLP-1RAs in older patients with diabetes, plus blood pressure control trials.","limitations":"Narrative review, not systematic. May not cover all evidence. Older adults are heterogeneous; findings may not apply to the most frail individuals."},{"rthcId":"RPEP-13443","title":"PGV001, a Multi-Peptide Personalized Neoantigen Vaccine Platform: Phase I Study in Patients with Solid and Hematologic Malignancies in the Adjuvant Setting.","authors":"Saxena, Mansi; Marron, Thomas U; Kodysh, Julia; Finnigan, John P; Onkar, Sayali; Kaminska, Anna; Tuballes, Kevin; Guo, Ruiwei; Sabado, Rachel Lubong; Meseck, Marcia; O'Donnell, Timothy J; Sebra, Robert P; Parekh, Samir; Galsky, Matthew D; Blasquez, Ana; Gimenez, Gustavo; Bicak, Mesude; Cimen Bozkus, Cansu; Delbeau-Zagelbaum, Daniela; Rodriguez, Denise; Acuna-Villaorduna, Ana; Misiukiewicz, Krzysztof J; Posner, Marshall R; Miles, Brett A; Irie, Hanna Y; Tiersten, Amy; Doroshow, Deborah B; Wolf, Andrea; Mandeli, John; Brody, Rachel; Salazar, Andres M; Gnjatic, Sacha; Hammerbacher, Jeff; Schadt, Eric; Friedlander, Philip; Rubinsteyn, Alexander; Bhardwaj, Nina","year":2025,"journal":"Cancer discovery, 15(5), 930-947","doi":"10.1158/2159-8290.CD-24-0934","pmid":"40094414","tags":["cancer-oncology","clinical-trials"],"studyType":"phase 1 clinical trial","evidenceStrength":"moderate","keyFinding":"The PGV001 personalized neoantigen vaccine platform was feasible, safe, and triggered immune responses in patients with solid and blood cancers. It predicted immunogenic targets even in tumors with few mutations.","whyItMatters":"Personalized cancer vaccines are a frontier of immunotherapy. This Phase 1 trial shows the approach works safely across tumor types and has spawned three follow-up trials in glioblastoma, bladder cancer, and prostate cancer.","specificNumbers":"Phase 1 study in solid and hematologic malignancies. OpenVax pipeline predicted neoantigens across wide-ranging mutational burdens. Three additional trials launched (glioblastoma, urothelial cancer + ICI, prostate cancer).","methodology":"Phase 1, open-label study of the PGV001 personalized multi-peptide neoantigen vaccine in patients with solid and hematologic cancers in the adjuvant setting. Used OpenVax computational pipeline for neoantigen prediction.","limitations":"Phase 1 (safety/feasibility focus). Small sample size typical of Phase 1. No efficacy endpoints. Adjuvant setting only."},{"rthcId":"RPEP-13444","title":"Design of a stapled peptide that binds to the Ebola virus matrix protein dimer interface.","authors":"Saxena, Roopashi; Wright, Madison M; Rathman, Benjamin M; Karki, Ukesh; Chapagain, Prem P; Del Valle, Juan R; Stahelin, Robert V","year":2025,"journal":"RSC chemical biology, 6(6), 963-974","doi":"10.1039/d5cb00048c","pmid":"40343175","tags":["antimicrobial-peptides","drug-discovery-screening"],"studyType":"laboratory study","evidenceStrength":"preliminary","keyFinding":"A stapled peptide designed to mimic a helix in the Ebola virus VP40 protein bound to VP40 with micromolar affinity and shifted its dimer-monomer balance. This is the first small molecule shown to disrupt VP40 dimerization.","whyItMatters":"Ebola virus assembly depends on VP40 dimerization. Disrupting this process with a designed peptide opens a new avenue for antiviral development against this deadly virus.","specificNumbers":"VP40 is 326 amino acids. Stapled peptide with di-cysteine staple achieved micromolar binding affinity. Confirmed by microscale thermophoresis, isothermal titration calorimetry, and size exclusion chromatography.","methodology":"Designed constrained peptide mimics of VP40 alpha-2 helix based on crystal structures. Screened by thermal shift assay. Confirmed binding by microscale thermophoresis and isothermal titration calorimetry. Dimer disruption assessed by size exclusion chromatography.","limitations":"In vitro binding study only. No cell-based or animal antiviral data. Micromolar affinity may be insufficient for therapeutic use without optimization."},{"rthcId":"RPEP-13445","title":"On the Pleiotropic Actions of Glucagon-like Peptide-1 in Its Regulation of Homeostatic and Hedonic Feeding.","authors":"Sayers, Sarah; Wagner, Ed","year":2025,"journal":"International journal of molecular sciences, 26(8)","doi":"10.3390/ijms26083897","pmid":"40332762","tags":["glp1-receptor-agonists","neuroscience-neurological","weight-management"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"GLP-1 reduces both normal hunger and reward-driven eating through different brain circuits. It inhibits hunger-promoting AgRP/NPY neurons, reward-linked dopamine neurons, and activates PACAP neurons in the hypothalamus.","whyItMatters":"Understanding how GLP-1 suppresses appetite through multiple brain pathways helps explain why GLP-1 drugs are effective for weight loss and may guide development of more targeted treatments.","specificNumbers":"GLP-1 (30 pmol) injected into arcuate nucleus decreased homeostatic feeding. Intra-VMN GLP-1 effects were blocked by exendin 9-39 (GLP1R antagonist). GLP-1 produced outward currents in NPY/AgRP and A10 dopamine neurons, inward current in VMN PACAP neurons.","methodology":"Electrophysiology and behavioral studies in transgenic mice (AgRP-cre, TH-cre, PACAP-cre). Direct brain injections of GLP-1 into arcuate nucleus, ventral tegmental area, and ventromedial nucleus. Measured feeding, binge eating, and neuronal currents.","limitations":"Mouse study. Direct brain injections do not reflect how systemic GLP-1 drugs reach the brain. Transgenic models may not fully represent normal physiology."},{"rthcId":"RPEP-13446","title":"In Vitro Properties of WMRK-gH625, a Novel Hybrid Peptide against Multidrug-Resistant Pathogens.","authors":"Scaglione, Elena; Bellavita, Rosa; di Rosario, Martina; Falcigno, Lucia; Mantova, Giuseppe; Continisio, Leonardo; Pagliuca, Chiara; Vitiello, Mariateresa; Galdiero, Stefania; Colicchio, Roberta; Falanga, Annarita; Salvatore, Paola","year":2025,"journal":"ACS omega, 10(46), 55704-55715","doi":"10.1021/acsomega.5c07032","pmid":"41322634","tags":["antimicrobial-peptides","drug-discovery-screening"],"studyType":"laboratory study","evidenceStrength":"preliminary","keyFinding":"A new hybrid antimicrobial peptide (WMRK-gH625) combining a germ-killing peptide with a cell-penetrating peptide showed strong activity against drug-resistant bacteria including MRSA, with low toxicity to human cells.","whyItMatters":"Drug-resistant infections are a growing crisis. This fusion peptide approach combines membrane disruption with cell penetration, offering a new strategy that bacteria may find harder to resist.","specificNumbers":"Active against S. aureus, MRSA, E. coli, Salmonella enterica (reference and clinical strains). Bactericidal at 2x MIC or higher. Low cytotoxicity, low hemolytic activity, minimal oxidative stress in human cells.","methodology":"Designed and synthesized WMRK-gH625 fusion peptide. Tested antimicrobial activity (MIC, MBC), time-kill kinetics, membrane interaction, cytotoxicity, hemolytic activity, and oxidative stress in human cells.","limitations":"In vitro only. No animal or human efficacy data. Stability, bioavailability, and in vivo toxicity are unknown."},{"rthcId":"RPEP-13447","title":"Glucagon-like peptide-1 receptor agonists in patients with anthracycline related cardiac dysfunction.","authors":"Scalia, Isabel G; Ibrahim, Ramzi; Abdelnabi, Mahmoud; Pham, Hoang Nhat; Farina, Juan M; Pietri, Milagros Pereyra; Lee, Kwan S; Tamarappoo, Balaji K; Arsanjani, Reza; Ayoub, Chadi","year":2025,"journal":"Cardio-oncology (London, England), 11(1), 83","doi":"10.1186/s40959-025-00381-y","pmid":"40999487","tags":["glp1-receptor-agonists","cardiovascular","cancer-oncology"],"studyType":"retrospective cohort study","evidenceStrength":"low-moderate","keyFinding":"Cancer patients with anthracycline-induced heart damage who received GLP-1 receptor agonists had 38% lower hospitalization risk, 39% lower heart failure events, and 42% lower acute kidney failure compared to matched controls.","whyItMatters":"Anthracycline chemotherapy often damages the heart, and treatment options are limited. This is the first large dataset suggesting GLP-1RAs may protect against cardiac complications in cancer patients.","specificNumbers":"2,282 patients identified; 201 matched pairs analyzed. GLP-1RA group: hospitalization HR 0.617 (p<0.001), heart failure HR 0.612 (p=0.007), kidney failure HR 0.577 (p=0.002). Mean follow-up 295.4 days. No significant difference in mortality, atrial fibrillation, or cardiac arrest.","methodology":"Retrospective analysis of the TriNetX Research Network (2012-2022). Propensity-score matched 201 GLP-1RA users to 201 non-users among cancer patients with anthracycline-induced cardiac dysfunction.","limitations":"Retrospective observational design. Propensity matching cannot eliminate all confounding. Database study may have coding inaccuracies. No mortality benefit detected."},{"rthcId":"RPEP-13448","title":"Innovative Therapeutic Approaches Targeting Obesity: Can Flavonoids Improve the Efficacy of Anti-Obesogenic Drugs?","authors":"Scarpa, Emanuele-Salvatore; Amatori, Stefano; Caprioli, Giovanni; Maggi, Filippo; Moroncini, Gianluca; Balercia, Giancarlo; Giacchetti, Gilberta","year":2025,"journal":"International journal of molecular sciences, 26(20)","doi":"10.3390/ijms262010142","pmid":"41155431","tags":["weight-management","glp1-receptor-agonists","nutraceuticals-supplements"],"studyType":"narrative review","evidenceStrength":"not applicable (review)","keyFinding":"This review proposes combining flavonoids (natural plant compounds) with anti-obesity drugs like semaglutide and tirzepatide. Flavonoids can block fat cell formation, reduce inflammation, and influence epigenetic changes linked to obesity.","whyItMatters":"Current obesity drugs are effective but may benefit from adjunct therapies. Flavonoids are widely available, safe dietary compounds that target obesity through different mechanisms than GLP-1 drugs.","specificNumbers":"Not specified (review of in vitro and in vivo flavonoid studies)","methodology":"Narrative review identifying flavonoids with anti-adipogenic and anti-obesity effects from published in vitro and in vivo studies, and proposing combination strategies with approved anti-obesity drugs.","limitations":"Review only. No clinical data on flavonoid-drug combinations. In vitro anti-adipogenic effects may not translate to meaningful weight loss in humans. Bioavailability of dietary flavonoids is often low."},{"rthcId":"RPEP-13449","title":"Impact of spin-freezing parameters and excipient composition on product stability of a PEGylated peptide formulation.","authors":"Schaal, Zarah; Bockstal, Pieter-Jan Van; Lammens, Joris; Lenger, Julian H; Funke, Adrian P; Schneid, Stefan C; Beer, Thomas De","year":2025,"journal":"International journal of pharmaceutics, 683, 126007","doi":"10.1016/j.ijpharm.2025.126007","pmid":"40759220","tags":["peptide-manufacturing","drug-delivery-systems"],"studyType":"laboratory study","evidenceStrength":"preliminary","keyFinding":"For a PEGylated peptide drug, the choice of sugar excipient (trehalose, mannitol, or sucrose-mannitol) had a far greater impact on stability than spin-freezing parameters. Trehalose gave the best stability. Sucrose-mannitol degraded badly at high temperature.","whyItMatters":"Continuous freeze-drying is a promising manufacturing method for peptide drugs. This study shows that formulation choice matters more than processing conditions for product stability.","specificNumbers":"Three formulations tested: trehalose, mannitol, sucrose-mannitol (75:25). Four spin-freezing conditions. Storage at 2-8°C or 50°C for up to 13 weeks. Sucrose-mannitol showed cake collapse, browning, and degradation at 50°C.","methodology":"Compared trehalose, mannitol, and sucrose-mannitol formulations across four spin-freezing conditions. Evaluated peptide concentration, monomer content, and cake morphology after batch drying and accelerated/refrigerated storage.","limitations":"Single PEGylated peptide studied. Results may not generalize to all peptide drugs. 50°C is an accelerated stress condition, not normal storage."},{"rthcId":"RPEP-13450","title":"The development of growth hormone-releasing hormone analogs: Therapeutic advances in cancer, regenerative medicine, and metabolic disorders.","authors":"Schally, Andrew V; Cai, Renzhi; Zhang, Xianyang; Sha, Wei; Wangpaichitr, Medhi","year":2025,"journal":"Reviews in endocrine & metabolic disorders, 26(3), 385-396","doi":"10.1007/s11154-024-09929-2","pmid":"39592529","tags":["hormones-endocrine","cancer-oncology","regenerative-medicine"],"studyType":"narrative review","evidenceStrength":"not applicable (review)","keyFinding":"GHRH agonists promote tissue regeneration, improve heart function, and help islet survival in diabetes models. GHRH antagonists show antitumor activity against lung, prostate, breast, and GI cancers with minimal toxicity in preclinical studies.","whyItMatters":"GHRH analogs may have therapeutic uses far beyond growth hormone regulation, spanning cancer, regenerative medicine, inflammation, and neurodegeneration.","specificNumbers":"GHRH antagonist series MIA and AVR demonstrated antitumor activity in preclinical models of lung, prostate, breast, and gastrointestinal cancers.","methodology":"Narrative review of preclinical and early clinical literature on GHRH agonists and antagonists across oncology, regenerative medicine, and metabolic disorders.","limitations":"Review based mostly on preclinical data. Few human clinical trials. Long-term safety of GHRH analogs in these new indications is unknown."},{"rthcId":"RPEP-13451","title":"Proteomic signatures reflect effects of semaglutide treatment for MASH.","authors":"Schattenberg, Jörn M; Grønbæk, Henning; Kliers, Iris; Ladelund, Steen; Long, Michelle T; Nygård, Sune Boris; Sanyal, Arun J; Davies, Melanie J","year":2025,"journal":"JHEP reports : innovation in hepatology, 7(10), 101521","doi":"10.1016/j.jhepr.2025.101521","pmid":"40980163","tags":["glp1-receptor-agonists","liver-gi","clinical-trials"],"studyType":"post-hoc analysis of randomized controlled trials","evidenceStrength":"moderate","keyFinding":"A blood protein test (SomaSignal) detected fatty liver disease components in STEP 1 and STEP 2 trial participants. Semaglutide 2.4 mg reduced the odds of having these markers by about 5-fold compared to placebo, correlating with liver biopsy findings from a separate trial.","whyItMatters":"Liver biopsies are invasive and impractical for large trials. This protein-based blood test could let researchers track liver disease improvement without biopsies, accelerating drug development for fatty liver disease.","specificNumbers":"SomaSignal steatosis prevalence: 43.2% (STEP 1), 71.7% (STEP 2). Semaglutide 2.4 mg odds ratio for improved liver disease stage: 5.26 (STEP 1, 95% CI 3.59-7.72), 4.90 (STEP 2, 95% CI 2.86-8.40), both p<0.0001. 68-week treatment.","methodology":"Post-hoc analysis of STEP 1 and STEP 2 RCTs using SomaSignal proteomics at baseline and week 68. Cross-validated against liver biopsy data from the Sema-MASH Phase IIb trial (72 weeks, once-daily semaglutide).","limitations":"Post-hoc analysis. SomaSignal is not yet validated as a diagnostic replacement for biopsy. STEP trials were not designed to study liver outcomes. Proteomics-based endpoints are surrogate measures."},{"rthcId":"RPEP-13452","title":"Neurodegeneration onset with glucagon-like peptide-1 receptor agonists in people with type 2 diabetes: a real-world multinational cohort study.","authors":"Schechter, Meir; Fishkin, Alisa; Mosenzon, Ofri; Sehtman-Shachar, Dvora R; Cukierman-Yaffe, Tali; Leibowitz, Gil; Aharon-Hananel, Genya","year":2025,"journal":"Cardiovascular diabetology, 24(1), 426","doi":"10.1186/s12933-025-02962-8","pmid":"41204243","tags":["glp1-receptor-agonists","neuroscience-neurological","aging-longevity"],"studyType":"retrospective cohort study","evidenceStrength":"moderate","keyFinding":"In over 214,000 matched patients with type 2 diabetes, GLP-1 receptor agonist users had 19% lower risk of new neurodegenerative disease compared to DPP-4 inhibitor users over 4 years. The association held for dementia and Alzheimer's but not Parkinson's disease.","whyItMatters":"Type 2 diabetes significantly increases dementia risk. This large real-world study adds to growing evidence that GLP-1 drugs may protect the brain, supporting the case for dedicated clinical trials.","specificNumbers":"214,442 matched individuals. Mean follow-up 4.0 years. Composite neurodegeneration HR 0.81 (95% CI 0.77-0.86). Dementia HR 0.76. Alzheimer's HR 0.77. Vascular dementia HR 0.75. Parkinson's HR 1.04 (not significant). Semaglutide HR 0.75, liraglutide HR 0.77, dulaglutide HR 0.82.","methodology":"Retrospective cohort using TriNetX platform (170M+ records). Propensity-score matched 1:1. GLP-1RA vs DPP-4i initiators (2010-2021). Cox regression for composite and individual neurodegenerative outcomes over up to 5 years. Separate analysis vs basal insulin.","limitations":"Observational design cannot prove causation. Potential residual confounding despite matching. Database study may have diagnostic coding inaccuracies. Parkinson's showed no benefit."},{"rthcId":"RPEP-13453","title":"Glucagon-like peptide-1 receptor agonists and alcohol use disorders: An emerging unexpected beneficial effect.","authors":"Scheen, André J","year":2025,"journal":"Diabetes, obesity & metabolism, 27(8), 4083-4091","doi":"10.1111/dom.16453","pmid":"40364515","tags":["glp1-receptor-agonists","neuroscience-neurological","mental-health"],"studyType":"comprehensive review","evidenceStrength":"not applicable (review)","keyFinding":"Across seven observational studies, GLP-1 receptor agonists reduced the prevalence of alcohol use disorder by 35% (HR 0.65) compared to non-GLP-1 therapy. Protection covered both new cases and relapses. Two available RCTs had inconclusive results.","whyItMatters":"Alcohol use disorder affects millions and has few effective treatments. If confirmed in ongoing trials, GLP-1 drugs could offer a new treatment approach targeting the brain's reward pathways.","specificNumbers":"7 observational cohort studies (12 paired comparisons). HR 0.65 (95% CI 0.56-0.74) for alcohol use disorder with GLP-1RA therapy. Protection for both incidence and recurrence. 2 RCTs available with inconclusive results.","methodology":"Comprehensive literature review of clinical studies (observational and controlled) examining GLP-1RA effects on alcohol use disorder in obese/T2DM patients. Included preclinical, genetic, and neuroimaging evidence.","limitations":"Observational studies cannot prove causation. Only 2 RCTs, both inconclusive. Confounding by indication possible. GLP-1RA users may differ systematically from non-users."},{"rthcId":"RPEP-13454","title":"Weight loss therapy and addiction: Increased risk after bariatric surgery but reduced risk with GLP-1 receptor agonists.","authors":"Scheen, André J","year":2025,"journal":"Diabetes & metabolism, 51(2), 101612","doi":"10.1016/j.diabet.2025.101612","pmid":"39818408","tags":["glp1-receptor-agonists","weight-management","mental-health"],"studyType":"comprehensive review","evidenceStrength":"not applicable (review)","keyFinding":"After bariatric surgery, the risk of alcohol use disorder roughly doubles after 2+ years. In contrast, GLP-1 receptor agonist therapy cuts the risk roughly in half. Similar divergent patterns appear for other addictive disorders.","whyItMatters":"Both bariatric surgery and GLP-1 drugs cause weight loss, but they have opposite effects on addiction risk. This has important implications for choosing between these approaches, especially in patients with addiction history.","specificNumbers":"11 observational studies (mostly gastric bypass): ~2x higher alcohol use disorder prevalence after >2 years post-surgery. 5 observational studies (mostly semaglutide): ~50% reduction in alcohol use disorder with GLP-1RA therapy.","methodology":"Literature review of clinical studies examining addictive disorders (alcohol, smoking, cannabis, cocaine, opioid) following bariatric surgery vs. GLP-1RA therapy in obese patients.","limitations":"All observational data. Confounding possible. Bariatric surgery patients may differ from GLP-1RA patients in ways that affect addiction risk. No head-to-head RCTs."},{"rthcId":"RPEP-13455","title":"The Anti-Inflammatory Effects of Liraglutide in Equine Inflammatory Joint Models.","authors":"Scheike, Ann-Sofie; Plomp, Saskia; Fugazzola, Maria Carlotta; Meurot, Coralie; Berenbaum, Francis; van Weeren, Paul René; Tryfonidou, Marianna Andriana; von Hegedus, Johannes Hendrick","year":2025,"journal":"Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 43(5), 893-903","doi":"10.1002/jor.26050","pmid":"39904754","tags":["glp1-receptor-agonists","immunology-inflammation","bone-joint-health"],"studyType":"animal study (equine)","evidenceStrength":"preliminary","keyFinding":"Liraglutide reduced the inflammatory marker CCL2 in horse joint cell cultures. However, when injected into inflamed pony joints in vivo, it did not significantly reduce inflammation or cartilage breakdown markers compared to placebo.","whyItMatters":"GLP-1 drugs have anti-inflammatory properties, but this study shows the effect seen in isolated cells may not translate to the complex environment of an inflamed joint.","specificNumbers":"7 Shetland ponies. 0.25 ng LPS used to induce synovitis bilaterally. 6 mg liraglutide vs. placebo per joint. CCL2 reduced in cell cultures (whole blood, PBMCs, chondrocytes, synoviocytes). No significant differences in any synovial fluid biomarker in vivo.","methodology":"In vitro: equine whole blood, PBMCs, chondrocytes, and synoviocytes stimulated with LPS or IL-1beta, treated with liraglutide. In vivo: bilateral intercarpal joint synovitis induced in 7 Shetland ponies, paired comparison of liraglutide vs. placebo per joint.","limitations":"Equine model may not translate to humans. Small sample (7 ponies). In vivo negative result despite in vitro positive. Single dose tested. Short-term acute model only."},{"rthcId":"RPEP-13456","title":"Characterization of [3H]Propionylated Human Peptide YY-A New Probe for Neuropeptide Y Y2 Receptor Binding Studies.","authors":"Schettler, Franziska; Gattor, Albert O; Koch, Pierre; Keller, Max","year":2025,"journal":"ACS pharmacology & translational science, 8(3), 785-799","doi":"10.1021/acsptsci.4c00666","pmid":"40109743","tags":["neuroscience-neurological","drug-discovery-screening"],"studyType":"laboratory study (tool development)","evidenceStrength":"preliminary","keyFinding":"A new tritium-labeled version of peptide YY works reliably for measuring drug binding at the Y2 receptor in both sodium-free and sodium-containing buffers, unlike previous tools that struggled in physiological conditions.","whyItMatters":"The Y2 receptor is a drug target for epilepsy and mood disorders. This new research tool enables more accurate screening of potential drugs under conditions that better mimic the body.","specificNumbers":"Kd = 0.016-0.067 nM in sodium-free buffer. Kd = 0.16-0.18 nM in sodium-containing buffer (175 mM Na+). Ki values from competition binding matched published Y2R binding affinities.","methodology":"Synthesized tritium-labeled PYY derivative by propionylation at Lys4. Characterized by saturation binding, kinetics, and competition binding assays on CHO cells expressing human Y2R.","limitations":"In vitro tool characterization only. Tested on one cell line. Does not directly translate to therapeutic development."},{"rthcId":"RPEP-13457","title":"Beyond Weight Loss: Comparative Effects of Tirzepatide Plus Low-Energy Ketogenic Versus Low-Calorie Diet on Hepatic Steatosis and Stiffness in MASLD.","authors":"Schiavo, Luigi; Santella, Biagio; Mingo, Monica; Rossetti, Gianluca; Orio, Marcello; Pilone, Vincenzo","year":2025,"journal":"Nutrients, 17(15)","doi":"10.3390/nu17152409","pmid":"40805994","tags":["glp1-receptor-agonists","liver-gi","weight-management"],"studyType":"prospective comparative study","evidenceStrength":"low-moderate","keyFinding":"Tirzepatide plus a low-energy ketogenic diet reduced liver fat (CAP) by 12.5% and liver stiffness (LSM) by 9.2% over 12 weeks, significantly more than tirzepatide plus a standard low-calorie diet. Weight loss was similar between groups.","whyItMatters":"Fatty liver disease affects millions. Pairing tirzepatide with a ketogenic diet may provide greater liver benefits than a standard diet, even when weight loss is the same.","specificNumbers":"60 patients (30 per group). CAP reduction: -12.5% with LEKT vs. less with LCD (between-group p=0.01). LSM reduction: -9.2% with LEKT (between-group p=0.03). Weight loss significant in both groups with no intergroup difference (p=0.665).","methodology":"Prospective study of 60 MASLD patients on tirzepatide, assigned to low-energy ketogenic therapy (LEKT) or conventional low-calorie diet (LCD) for 12 weeks. FibroScan for CAP and LSM at baseline and 12 weeks.","limitations":"Small sample (30 per group). Not randomized or blinded. 12 weeks is short. No liver biopsy confirmation. Diet adherence may vary."},{"rthcId":"RPEP-13458","title":"Preliminary Evidence Suggests That a 12-Week Treatment with Tirzepatide Plus Low-Energy Ketogenic Therapy Is More Effective than Its Combination with a Low-Calorie Diet in Preserving Fat-Free Mass, Muscle Strength, and Resting Metabolic Rate in Patients with Obesity.","authors":"Schiavo, Luigi; Santella, Biagio; Mingo, Monica; Rossetti, Gianluca; Orio, Marcello; Cobellis, Luigi; Maurano, Attilio; Iannelli, Antonio; Pilone, Vincenzo","year":2025,"journal":"Nutrients, 17(7)","doi":"10.3390/nu17071216","pmid":"40218974","tags":["glp1-receptor-agonists","weight-management","bone-joint-health"],"studyType":"prospective comparative study","evidenceStrength":"low-moderate","keyFinding":"Tirzepatide plus a ketogenic diet preserved muscle mass, muscle strength, and resting metabolic rate over 12 weeks, while tirzepatide plus a standard low-calorie diet led to significant losses in all three. Fat loss was greater with the ketogenic diet.","whyItMatters":"Muscle loss during weight loss drug therapy is a major concern. Pairing tirzepatide with a ketogenic diet may protect muscle while enhancing fat loss.","specificNumbers":"60 patients (30 per group). Both groups lost significant weight (p<0.03 each). TZP+LCD group: significant declines in FFM (p=0.028), muscle strength (p=0.034), and RMR (p<0.05). TZP+LEKT group: no significant changes in FFM, strength, or RMR. Between-group differences significant for all three (p<0.05).","methodology":"Prospective comparison of 60 obese patients on tirzepatide, assigned to LEKT or LCD for 12 weeks. Measured body weight, fat mass, fat-free mass, muscle strength, and resting metabolic rate at baseline and week 12.","limitations":"Small sample. Not randomized or blinded. Short duration. Specific dietary adherence not verified objectively. No long-term follow-up."},{"rthcId":"RPEP-13459","title":"Enzymatically Crafted Bacterial Cellulose Nanoparticles Functionalized With Antimicrobial Peptides: Toward Sustainable Antimicrobial Formulations.","authors":"Schibeci, Martina; Gaglione, Rosa; Russo, Noemi; Velotta, Raffaele; Della Ventura, Bartolomeo; Arciello, Angela","year":2025,"journal":"Biotechnology journal, 20(2), e202400573","doi":"10.1002/biot.202400573","pmid":"39989267","tags":["antimicrobial-peptides","drug-delivery-systems"],"studyType":"laboratory study","evidenceStrength":"preliminary","keyFinding":"Bacterial cellulose nanoparticles produced by enzymatic hydrolysis successfully carried an antimicrobial peptide derived from human apolipoprotein B. The system showed strong antimicrobial activity in lab tests and good compatibility with human skin cells.","whyItMatters":"Antimicrobial peptides degrade quickly in the body. A biodegradable, sustainable nanoparticle delivery system could extend their usefulness and bring them closer to practical medical use.","specificNumbers":"Bacterial cellulose nanoparticles produced by Komagataeibacter xylinus. Enzymatic hydrolysis using Trichoderma reesei cellulases. Peptide derived from human apolipoprotein B. Non-covalent binding of peptide to nanoparticles.","methodology":"Produced bacterial cellulose, hydrolyzed into nanoparticles with cellulases, functionalized with AMP via non-covalent binding. Tested antimicrobial activity in vitro and biocompatibility on human skin cells. Evaluated storage stability.","limitations":"In vitro only. No in vivo efficacy or pharmacokinetic data. Non-covalent peptide binding may be unstable under physiological conditions. Scalability not yet demonstrated."},{"rthcId":"RPEP-13460","title":"Treatment Preferences For Comorbid Obesity and Obstructive Sleep Apnea (PRO-CON OSA) Survey: Patient and Provider Preferences for CPAP and/or Tirzepatide.","authors":"Schmickl, Christopher N; Tripipitsiriwat, Athiwat; Mokhlesi, Babak; Mallampalli, Monica; Nokes, Brandon; Kundel, Vaishnavi; Page, Kathy; Finch, Christina; Donovan, Lucas; Tadros, Mira; Aysola, Ravi S; Zinchuk, Andrey; Zvenyach, Tracy; Badr, M Safwan; Patel, Sanjay R; Orr, Jeremy E; Owens, Robert L; Lindsell, Chris; Martin, Jennifer L; Malhotra, Atul","year":2025,"journal":"medRxiv : the preprint server for health sciences","doi":"10.1101/2025.10.02.25337176","pmid":"41256163","tags":["glp1-receptor-agonists","respiratory","weight-management"],"studyType":"cross-sectional survey","evidenceStrength":"low","keyFinding":"Both patients and providers found CPAP and tirzepatide acceptable for obesity with sleep apnea. Patients preferred tirzepatide (48% vs 21%), while providers preferred CPAP (52% vs 27%). Both groups supported combination therapy.","whyItMatters":"Tirzepatide was recently approved for obstructive sleep apnea with obesity. Understanding patient and provider preferences is essential for designing comparative effectiveness trials and implementing shared decision-making.","specificNumbers":"461 patients, 114 providers surveyed. 70% found both treatments at least somewhat acceptable. Patient preference: 48% tirzepatide vs 21% CPAP. Provider preference: 52% CPAP vs 27% tirzepatide. Combination therapy support: 61% patients vs 86% providers.","methodology":"Online survey (Nov 2024-Aug 2025) of US adults with OSA/obesity and sleep medicine providers. Assessed treatment acceptability, preferences, and informational needs.","limitations":"Survey study, not a clinical trial. Self-selected respondents may not represent all patients/providers. Preprint, not yet peer reviewed. Assumed equal effectiveness in preference questions."},{"rthcId":"RPEP-13461","title":"Self-Emulsifying delivery systems for oral administration of exenatide: Hydrophobic ion pairs vs. Dry reverse micelles.","authors":"Schmidt, Marlene Ramona; Ebert, Melanie Lena; Kiechle, Magnus Andre; Zöller, Katrin; Laffleur, Flavia; Bernkop-Schnürch, Andreas","year":2025,"journal":"International journal of pharmaceutics, 678, 125711","doi":"10.1016/j.ijpharm.2025.125711","pmid":"40360092","tags":["glp1-receptor-agonists","drug-delivery-systems"],"studyType":"laboratory study (preclinical pharmacology)","evidenceStrength":"preliminary","keyFinding":"Two oral delivery strategies for exenatide (hydrophobic ion pairing and dry reverse micelles) both achieved about 18% oral bioavailability in animals compared to IV injection. The ion pair version gave better controlled release; the micelle version used safer excipients.","whyItMatters":"GLP-1 drugs like exenatide currently require injection. Achieving 18% oral bioavailability is a meaningful step toward an oral formulation that could improve patient convenience and adherence.","specificNumbers":"Droplet sizes 95-110 nm. Log DSEDDS/AQ: 2.13 (HIP), 2.05 (dRM). Relative oral bioavailability: 18.08% (ExeHIP), 17.06% (ExedRM) vs. IV. 0.6% natamycin content. All excipients in dRM have GRAS status.","methodology":"Synthesized exenatide-loaded SEDDS via hydrophobic ion pairing (HIP) and dry reverse micelles (dRM). Characterized droplet size, lipophilicity, and stability. In vivo bioavailability study comparing oral SEDDS to IV exenatide.","limitations":"Animal study (species not specified). Oral bioavailability in humans may differ significantly. Long-term stability and GI tolerability not assessed. No comparison to existing injectable formulations for clinical outcomes."},{"rthcId":"RPEP-13462","title":"Tuft cells trigger neurogenic inflammation in the urethra.","authors":"Schmidt, Patricia; Pfeil, Uwe; Lafee, Mahmoud; Petersen, Swantje; Perniss, Alexander; Keshavarz, Maryam; Das, Debajyoti; Wyatt, Amanda; Boehm, Ulrich; Schütz, Burkhard; Kummer, Wolfgang; Deckmann, Klaus","year":2025,"journal":"Cell reports, 44(10), 116370","doi":"10.1016/j.celrep.2025.116370","pmid":"41032411","tags":["neuroscience-neurological","immunology-inflammation"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Specialized sensor cells (tuft cells) in the mouse urethra trigger local inflammation by releasing acetylcholine, which causes nearby nerve endings to release substance P and CGRP. This represents a newly discovered local defense mechanism.","whyItMatters":"Tuft cells were known to trigger bladder reflexes. This study reveals they also cause local inflammation in the urethra, adding a new layer to how the urinary tract defends against infection.","specificNumbers":"Neuropeptides released: substance P and CGRP. Signaling: via nicotinic acetylcholine receptors. In vivo: denatonium (a bitter compound) induced plasma extravasation (a sign of inflammation). Effect blocked in Trpm5 knockout mice and by neurokinin-1 receptor blockade.","methodology":"Mouse urethral tissue imaging, optogenetic activation of tuft cells, neuropeptide release measurement from explanted urethrae, in vivo plasma extravasation assay, Trpm5 knockout mice, and pharmacological receptor blockade.","limitations":"Mouse study only. Human urethral tuft cells may function differently. Induced inflammation model may not reflect natural infection. No clinical data."},{"rthcId":"RPEP-13463","title":"Effects of liraglutide on body composition in people living with obesity or overweight: A systematic review.","authors":"Schmidt, Pedro Henrique Siedschlag; Pasqualotto, Eric; Dos Santos, Henrique Vilar; de Souza, Lis Sodré Nonato; Dos Santos, Bruno Eulálio; Chavez, Matheus Pedrotti; Ferreira, Rafael Oliva Morgado; Hohl, Alexandre; Ronsoni, Marcelo Fernando; van de Sande-Lee, Simone","year":2025,"journal":"Obesity research & clinical practice, 19(1), 11-18","doi":"10.1016/j.orcp.2025.01.009","pmid":"39904668","tags":["glp1-receptor-agonists","weight-management"],"studyType":"systematic review","evidenceStrength":"moderate","keyFinding":"Across 15 RCTs with 960 participants, liraglutide consistently reduced total weight, fat mass, and visceral fat (12.5-23% reduction) compared to placebo. Lean mass results were mixed, with some studies showing preservation and others showing losses.","whyItMatters":"Visceral fat is the most dangerous type for heart and metabolic health. Liraglutide's consistent visceral fat reduction supports its role beyond simple weight loss.","specificNumbers":"15 RCTs, 960 participants. Visceral adipose tissue reductions ranged from 12.5% to 23%. Significant reductions in total weight and fat mass across studies. Lean mass outcomes variable.","methodology":"Systematic search of PubMed, Embase, and Cochrane Library through June 2024. Included RCTs comparing liraglutide to placebo with body composition outcomes.","limitations":"Could not perform meta-analysis due to inconsistent reporting. Lean mass data were variable and hard to interpret. Individual-level data not available. Most studies used liraglutide 3.0 mg."},{"rthcId":"RPEP-13464","title":"The PSD-95 inhibitor NA-1 is delivered to the brain upon nasal administration with uptake into the olfactory bulb improved by co-administration with the cell-penetrating peptides lowPro and Tat.","authors":"Schmidt, Solveig Elle; Joensen, Gunhild; Sandbjerg, Camilla; Thaysen, Maria; Gammelgaard, Bente; Schindowski, Katharina; Kristensen, Mie","year":2025,"journal":"Drug delivery and translational research","doi":"10.1007/s13346-025-01842-8","pmid":"40180762","tags":["neuroscience-neurological","drug-delivery-systems"],"studyType":"animal study (preclinical drug delivery)","evidenceStrength":"preliminary","keyFinding":"Nasal delivery of the neuroprotective peptide NA-1 reached the brain in mice, especially the olfactory bulb. Co-administering cell-penetrating peptides Tat and LowPro enhanced brain delivery while reducing off-target tissue distribution compared to IV.","whyItMatters":"NA-1 shows promise for stroke but interacts with clot-busting drugs when given by IV. Nasal delivery could bypass this problem and get the drug to the brain more directly.","specificNumbers":"NA-1 reached olfactory bulb after nasal administration. Tat and LowPro co-administration enhanced olfactory bulb delivery. Significantly lower off-target tissue distribution vs. IV. PenShuf improved permeability but compromised barrier integrity in vitro.","methodology":"Porcine primary olfactory model for in vitro permeability testing. In vivo nasal administration in mice with brain and tissue biodistribution analysis. Compared to IV NA-1. Tested co-administration with cell-penetrating peptides Tat, LowPro, and PenShuf.","limitations":"Mouse and porcine models only. Human nasal anatomy and physiology differ. Olfactory bulb delivery may not reach deeper brain regions affected by stroke. Dose optimization not performed."},{"rthcId":"RPEP-13465","title":"Amphipathic Proline-Rich Cell Penetrating Peptides for Targeting Mitochondria.","authors":"Schmitt, Adeline; Wennemers, Helma","year":2025,"journal":"ACS chemical biology, 20(9), 2298-2307","doi":"10.1021/acschembio.5c00479","pmid":"40826959","tags":["drug-delivery-systems","cell-biology"],"studyType":"laboratory study","evidenceStrength":"preliminary","keyFinding":"Rigid proline-based peptides with cationic and hydrophobic groups arranged along a helical backbone achieved enhanced cell entry and selective accumulation in mitochondria. The peptides showed time-dependent redistribution from other compartments to mitochondria.","whyItMatters":"Many diseases involve mitochondrial dysfunction. Designing peptides that reliably and selectively reach mitochondria could enable targeted delivery of drugs to this key organelle.","specificNumbers":"Polyproline II (PPII) helical backbone. Cationic guanidinium groups and hydrophobic cyclohexyl groups aligned along helix edges. Time-dependent redistribution leading to prolonged mitochondrial residency.","methodology":"Synthesized amphipathic oligoprolines with systematic variations in hydrophobicity. Compared rigid PPII helix peptides to flexible analogs. Assessed cellular uptake and mitochondrial selectivity using fluorescence microscopy and tracking.","limitations":"In vitro cell culture study only. No therapeutic cargo tested. Mitochondrial targeting efficiency in vivo is unknown. Cytotoxicity at higher concentrations not fully characterized."},{"rthcId":"RPEP-13466","title":"Cutting-Edge Approaches to Obesity Management: The Latest Pharmacological Options.","authors":"Schmitz, Sarah H; Saunders, Katherine H; Aronne, Louis J","year":2025,"journal":"Endocrinology and metabolism clinics of North America, 54(1), 85-102","doi":"10.1016/j.ecl.2024.09.003","pmid":"39919879","tags":["weight-management","glp1-receptor-agonists","clinical-trials"],"studyType":"clinical review","evidenceStrength":"not applicable (review)","keyFinding":"This review summarizes all seven FDA-approved anti-obesity medications including liraglutide, semaglutide, and tirzepatide, covering their trial data, dosing, side effects, and contraindications. Obesity requires chronic medication use.","whyItMatters":"Provides clinicians with a comprehensive, practical reference for prescribing the current range of obesity medications.","specificNumbers":"Seven FDA-approved drugs: phentermine, orlistat, phentermine/topiramate ER, naltrexone SR/bupropion SR, liraglutide 3.0 mg, semaglutide 2.4 mg, tirzepatide.","methodology":"Review of Phase 3 clinical trial data leading to FDA approval for each medication, plus clinical prescribing information.","limitations":"Review article, not primary research. May not capture the most recent post-marketing data. Head-to-head comparisons between all agents are limited."},{"rthcId":"RPEP-13467","title":"GLP-1 Receptor Agonists for Kidney Transplant Recipients.","authors":"Schmitz, Sarah H; Orandi, Babak J","year":2025,"journal":"Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association","doi":"10.1093/ndt/gfaf199","pmid":"41026089","tags":["glp1-receptor-agonists","kidney-renal","safety-tolerability"],"studyType":"narrative review","evidenceStrength":"not applicable (review)","keyFinding":"GLP-1 receptor agonists appear generally safe in kidney transplant recipients without increased graft rejection, pancreatitis, or immunosuppressive drug interactions. However, GI side effects and early discontinuation are common, and evidence is limited.","whyItMatters":"Kidney transplant recipients have high rates of obesity, diabetes, and heart disease. GLP-1RAs could address all three, but safety concerns around graft rejection and drug interactions have limited their use.","specificNumbers":"Not specified (narrative review of small retrospective and prospective studies). References SELECT, FLOW, and SMART trials for non-transplant context.","methodology":"Narrative review of retrospective and prospective studies of GLP-1RAs in kidney transplant recipients, plus key non-transplant cardiovascular and kidney outcome trials.","limitations":"Small sample sizes across available studies. Short follow-up. Potential selection bias. No randomized trials in transplant recipients. Translating non-transplant trial data requires caution."},{"rthcId":"RPEP-13468","title":"Using muscle homing peptide CyPep10 to deliver phosphorodiamidate morpholino oligomers in the mdx mouse.","authors":"Schneider, Anne-Fleur E; Tanganyika-de Winter, Christa L; Jirka, Silvana M G; Tan, Xuyu; Thompson, Emily G; Ha, Kristen; Mitra, Anindita; Garcia, Stephanie; Luimes, Marleen; Oliver, Ryan A; Guerlavais, Vincent; Aartsma-Rus, Annemieke","year":2025,"journal":"Molecular therapy. Nucleic acids, 36(3), 102625","doi":"10.1016/j.omtn.2025.102625","pmid":"40777739","tags":["drug-delivery-systems","genetic-disorders"],"studyType":"animal study (preclinical gene therapy)","evidenceStrength":"preliminary","keyFinding":"The muscle-homing peptide CyPep10 increased delivery of antisense oligonucleotides (PMOs) to muscle tissue in mdx mice. However, this alone did not increase exon skipping or dystrophin restoration. Adding a cell-penetrating peptide slightly improved exon skipping beyond CPP-PMO alone.","whyItMatters":"Duchenne muscular dystrophy has limited treatments. Getting antisense drugs into muscle cells is a key challenge. This study shows that tissue targeting and cell entry are separate hurdles that both need solving.","specificNumbers":"CyPep10 (CP10) conjugated to PMO ASOs. Significantly increased muscle tissue PMO concentration. No significant increase in exon skipping or dystrophin restoration with CP10-PMO alone. CP10+CPP-PMO showed slightly greater exon skipping than CPP-PMO alone.","methodology":"Conjugated CyPep10 to PMO antisense oligonucleotides. Tested in mdx mouse model of DMD. Measured tissue distribution, exon skipping efficiency, and dystrophin restoration. Compared CP10-PMO, CPP-PMO, and CP10+CPP-PMO.","limitations":"Mouse model only. Results may not translate to human DMD. CP10-PMO alone was ineffective for the functional endpoint. Small improvements with dual conjugation need optimization."},{"rthcId":"RPEP-13469","title":"CVOT summit report 2024: new cardiovascular, kidney, and metabolic outcomes.","authors":"Schnell, Oliver; Almandoz, Jaime; Anderson, Lisa; Barnard-Kelly, Katharine; Battelino, Tadej; Blüher, Matthias; Busetto, Luca; Catrinou, Doina; Ceriello, Antonio; Cos, Xavier; Danne, Thomas; Dayan, Colin M; Del Prato, Stefano; Fernández-Fernández, Beatriz; Fioretto, Paola; Forst, Thomas; Gavin, James R; Giorgino, Francesco; Groop, Per-Henrik; Harsch, Igor A; Heerspink, Hiddo J L; Heinemann, Lutz; Ibrahim, Mahmoud; Jadoul, Michel; Jarvis, Sarah; Ji, Linong; Kanumilli, Naresh; Kosiborod, Mikhail; Landmesser, Ulf; Macieira, Sofia; Mankovsky, Boris; Marx, Nikolaus; Mathieu, Chantal; McGowan, Barbara; Milenkovic, Tatjana; Moser, Othmar; Müller-Wieland, Dirk; Papanas, Nikolaos; Patel, Dipesh C; Pfeiffer, Andreas F H; Rahelić, Dario; Rodbard, Helena W; Rydén, Lars; Schaeffner, Elke; Spearman, C Wendy; Stirban, Alin; Tacke, Frank; Topsever, Pinar; Van Gaal, Luc; Standl, Eberhard","year":2025,"journal":"Cardiovascular diabetology, 24(1), 187","doi":"10.1186/s12933-025-02700-0","pmid":"40316962","tags":["glp1-receptor-agonists","cardiovascular","kidney-renal"],"studyType":"conference report / review","evidenceStrength":"not applicable (conference summary)","keyFinding":"The 10th CVOT Summit reviewed major cardiovascular, kidney, and metabolic outcome trial results for empagliflozin, semaglutide, tirzepatide, and finerenone across heart failure, CKD, sleep apnea, and MASLD.","whyItMatters":"This summit captures the latest landscape of cardiometabolic outcome trials, highlighting how GLP-1RAs, SGLT2 inhibitors, and finerenone are reshaping treatment across multiple organ systems.","specificNumbers":"Trials discussed: EMPACT-MI (empagliflozin), STEP-HFpEF-DM and FLOW (semaglutide), SURMOUNT-OSA and SUMMIT (tirzepatide), FINEARTS-HF (finerenone). Conference held Dec 5-6, 2024.","methodology":"Conference proceedings report summarizing presentations and discussions from the 10th CVOT Summit.","limitations":"Conference summary, not primary research. May reflect selected presentations rather than comprehensive evidence review. Some discussed trials may have preliminary data."},{"rthcId":"RPEP-13470","title":"Progastrin-Releasing Peptide and Procalcitonin as Additional Markers in the Diagnostic Workup for Medullary Thyroid Carcinoma.","authors":"Schonebaum, Leonoor E; van den Berg, Sjoerd A A; van Balkum, Mathé; Visser, W Edward; Giovanella, Luca; Peeters, Robin P","year":2025,"journal":"Thyroid : official journal of the American Thyroid Association, 35(9), 1030-1038","doi":"10.1089/thy.2024.0293","pmid":"40576708","tags":["cancer-oncology","hormones-endocrine"],"studyType":"prospective multicohort study","evidenceStrength":"moderate","keyFinding":"Combining calcitonin and procalcitonin in a two-step test achieved 100% sensitivity and 99.7% specificity for diagnosing medullary thyroid carcinoma. Progastrin-releasing peptide alone had low sensitivity (69.2%) and added no diagnostic value.","whyItMatters":"Calcitonin testing for medullary thyroid cancer has a high false-positive rate. Adding procalcitonin as a second step in the 10-100 pg/mL calcitonin range nearly eliminates false positives while catching all true cases.","specificNumbers":"396 patients total (335 discovery, 61 validation). 44 MTC, 186 other thyroid cancers, 166 benign. CT+PCT combination: 100% sensitivity, 100% NPV, 99.7% specificity, 97.7% PPV. ProGRP sensitivity only 69.2%.","methodology":"Prospective study in patients undergoing thyroid surgery. Discovery cohort (Netherlands, 2013-2025) and validation cohort (Switzerland). Preoperative serum calcitonin, procalcitonin, proGRP, and CEA measured. Two-step diagnostic approach tested.","limitations":"Single-center discovery cohort in a tertiary referral center. Moderate validation cohort size. Performance in low-prevalence screening settings may differ."},{"rthcId":"RPEP-13471","title":"A Hypothesis That Glucagon-like Peptide-1 Receptor Agonists Exert Immediate and Multifaceted Effects by Activating Adenosine Monophosphate-Activate Protein Kinase (AMPK).","authors":"Schooling, C Mary; Yang, Guoyi; Soliman, Ghada A; Leung, Gabriel M","year":2025,"journal":"Life (Basel, Switzerland), 15(2)","doi":"10.3390/life15020253","pmid":"40003662","tags":["glp1-receptor-agonists","cardiovascular","cell-biology"],"studyType":"hypothesis / perspective article","evidenceStrength":"not applicable (hypothesis)","keyFinding":"The authors propose that GLP-1 receptor agonists work partly by activating AMPK, a master metabolic sensor. This could explain why cardiovascular and kidney benefits appear before weight loss and why GLP-1 drugs share mechanisms with metformin, statins, and exercise.","whyItMatters":"Understanding the rapid, weight-loss-independent benefits of GLP-1 drugs could lead to better combination therapies and help identify which patients will benefit most.","specificNumbers":"Not applicable (hypothesis paper reviewing existing evidence)","methodology":"Hypothesis paper reviewing evidence from randomized controlled trials and mechanistic studies on GLP-1RAs and AMPK-activating therapies.","limitations":"Hypothesis, not proven. AMPK activation by GLP-1RAs has not been definitively demonstrated as the primary mechanism. May oversimplify complex multi-pathway drug effects."},{"rthcId":"RPEP-13472","title":"Differential risk assessment in persons at risk of type 2 diabetes using urinary peptidomics.","authors":"Schork, Anja; Fritsche, Andreas; Schleicher, Erwin D; Peter, Andreas; Heni, Martin; Stefan, Norbert; von Schwartzenberg, Reiner Jumpertz; Guthoff, Martina; Mischak, Harald; Siwy, Justyna; Birkenfeld, Andreas L; Wagner, Robert","year":2025,"journal":"Metabolism: clinical and experimental, 167, 156174","doi":"10.1016/j.metabol.2025.156174","pmid":"40023439","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13473","title":"GLP-1/GIP/GCG receptor triagonist (IUB447) enhances insulin secretion via GLP-1 receptor and Gαq signalling pathway in mice.","authors":"Schreier, Pascale C F; Beyerle, Philipp; Boulassel, Severin; Beck, Andreas; Novikoff, Aaron; Reinach, Peter S; Boekhoff, Ingrid; Breit, Andreas; Neuberger, Arthur; Müller, Timo D; Serrano, Alberto Cebrian; Gudermann, Thomas; Khajavi, Noushafarin","year":2025,"journal":"Diabetologia, 68(11), 2567-2580","doi":"10.1007/s00125-025-06525-0","pmid":"40924112","tags":["glp1-receptor-agonists","metabolic-disorders"],"studyType":"animal study (mechanistic)","evidenceStrength":"preliminary","keyFinding":"A triple-receptor agonist targeting GLP-1, GIP, and glucagon receptors boosted insulin secretion primarily through the GLP-1 receptor and the Gαq-TRPM5 signaling pathway in mouse islets. Removing this pathway eliminated the drug's blood sugar benefits in obese mice.","whyItMatters":"Triple-receptor agonists are the next generation of obesity and diabetes drugs. Understanding that their insulin-boosting power comes mainly through GLP-1R and Gαq signaling helps guide future drug design.","specificNumbers":"IUB447 triagonist tested. Enhanced insulin secretion more than co-administered mono-agonists. Effect unchanged without GIP or glucagon receptors. Effect eliminated without both GLP-1R and GIPR, or with GLP-1R antagonist exendin-3(9-39). Gαq blocker YM254890 and TRPM5 blocker TPPO suppressed the effect. Trpm5 knockout mice showed no glycemic benefit.","methodology":"Isolated islets from WT, Gipr-/-, Gcgr-/-, Glp1r/Gipr double-KO, and Trpm5-/- mice. Measured glucose-stimulated insulin secretion with triagonist vs mono-agonists. In vivo metabolic testing in WT and Trpm5-/- mice on chow and high-fat diets.","limitations":"Mouse study only. Human islet signaling may differ. Single triagonist compound tested. In vivo results limited to one mouse strain and diet model."},{"rthcId":"RPEP-13474","title":"A randomized, double-blind, placebo-controlled trial of N-acetylcysteine as an adjuvant treatment for alcohol use disorder.","authors":"Schuch, Jaqueline B; Hansen, Fernanda; Hartmann, Thiago; Benzano, Daniela; Gomes, Henrique M; Moreira, José Cláudio F; Pechansky, Flavio; Kessler, Felix H P; Galland, Fabiana; Silvello, Daiane; Sordi, Anne O; von Diemen, Lisia","year":2025,"journal":"Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999), 47, e20243541","doi":"10.47626/1516-4446-2024-3541","pmid":"41021585","tags":["mental-health","nutraceuticals-supplements","clinical-trials"],"studyType":"randomized controlled trial","evidenceStrength":"moderate","keyFinding":"N-acetylcysteine as an add-on treatment for alcohol use disorder did not improve treatment adherence, relapse rates, or clinical outcomes compared to placebo in a 9-week trial of 53 inpatients. It did affect neuropeptide Y levels and oxidative stress markers.","whyItMatters":"N-acetylcysteine has been proposed as an adjunct therapy for addiction. This trial found no clinical benefit for alcohol use disorder, though biomarker changes suggest biological activity that may need larger trials to evaluate.","specificNumbers":"53 patients (25 NAC, 28 placebo). Completion: 64% NAC, 60.7% placebo. Neuropeptide Y increased in NAC group by end of study. Superoxide dismutase decreased in NAC group. Similar relapse time, adherence, and clinical improvement between groups.","methodology":"9-week randomized, double-blind, placebo-controlled trial in 53 inpatients with alcohol use disorder. Measured neuropeptide Y, oxidative stress markers, inflammatory biomarkers, and hepatic parameters at 3 time points.","limitations":"Small sample size. Inpatient population with severe alcohol use disorder. Short follow-up. Underpowered for clinical outcomes. High dropout in both groups."},{"rthcId":"RPEP-13475","title":"GLP-1R Agonism Directly Improves the Pumping Capacity of Murine Collecting Lymphatic Vessels.","authors":"Schulz, Mary E; Akerstrom, Victoria L; Dayan, Joseph H; Castorena-Gonzalez, Jorge A","year":2025,"journal":"bioRxiv : the preprint server for biology","doi":"10.64898/2025.12.26.696603","pmid":"41509291","tags":["glp1-receptor-agonists","cardiovascular"],"studyType":"animal study (mechanistic)","evidenceStrength":"preliminary","keyFinding":"GLP-1 receptors are expressed specifically on collecting lymphatic vessel cells (not capillary lymphatics). Semaglutide directly improved lymphatic pumping capacity in healthy, obese, and high-cholesterol mice by causing vasodilation through nitric oxide and reactive oxygen species pathways.","whyItMatters":"This is the first evidence that GLP-1 drugs directly improve lymphatic vessel function, independent of weight loss. This could explain why these drugs help with lymphedema and may open a new therapeutic application.","specificNumbers":"GLP-1R expression detected in collecting lymphatic endothelial cells (LECs) but absent in capillary LECs. Semaglutide caused vasodilation and increased pumping capacity in WT, DIO, and ApoE KO mice. ApoE KO lymphatic dysfunction was restored by semaglutide. Mediated partly by NO and NADPH oxidase-ROS.","methodology":"Single-cell RNA sequencing and confocal microscopy for GLP-1R localization. Pressure myography to measure contractile function of isolated collecting lymphatics from WT, diet-induced obese, and ApoE knockout mice treated with semaglutide.","limitations":"Preprint (not peer reviewed). Mouse study only. Isolated vessel preparations may not reflect in vivo complexity. Human lymphatic GLP-1R expression not confirmed."},{"rthcId":"RPEP-13476","title":"SOUL searching in GLP-1 therapy: Oral semaglutide confirms cardioprotection in type 2 diabetes.","authors":"Schwarz, Christine Rode; Vilsbøll, Tina","year":2025,"journal":"Med (New York, N.Y.), 6(8), 100774","doi":"10.1016/j.medj.2025.100774","pmid":"40782670","tags":["glp1-receptor-agonists","cardiovascular","clinical-trials"],"studyType":"commentary / editorial","evidenceStrength":"not applicable (commentary)","keyFinding":"The SOUL trial demonstrated that oral semaglutide reduced major cardiovascular events by 14%, confirming that the tablet formulation provides the same heart protection as the injectable version.","whyItMatters":"Oral semaglutide is now the only non-injectable GLP-1 receptor agonist with proven cardiovascular protection, offering a needle-free option for high-risk type 2 diabetes patients.","specificNumbers":"14% reduction in major adverse cardiovascular events (MACE) with oral semaglutide in the SOUL trial.","methodology":"Commentary on the SOUL cardiovascular outcome trial results for oral semaglutide.","limitations":"Commentary, not primary research. Full SOUL trial details should be consulted for methods, populations, and limitations."},{"rthcId":"RPEP-13477","title":"Peptides Corresponding to the Receptor-Binding Domain (RBD) of Several SARS-CoV-2 Variants Of Concern Prevent Recognition of the Human ACE2 Receptor and Consecutive Cell Infections.","authors":"Schwarze, Mandy; Brakel, Alexandra; Hoffmann, Ralf; Krizsan, Andor","year":2025,"journal":"ChemMedChem, 20(7), e202400973","doi":"10.1002/cmdc.202400973","pmid":"39996354","tags":["antimicrobial-peptides","infection-immunity"],"studyType":"laboratory study","evidenceStrength":"preliminary","keyFinding":"Peptides from the SARS-CoV-2 spike protein receptor binding domain (sequence 392-421) blocked viral binding to ACE-2 and inhibited pseudovirus infection by 98.8% at 244 micromol/L. They worked across multiple variants and did not interfere with antibody binding.","whyItMatters":"New antiviral approaches are needed beyond vaccines. These peptides block viral entry, work alongside antibodies, and remain active across variants including BA.5 and KP.3.","specificNumbers":"Peptide p392wt (sequence 392-421). 98.8% ± 8.1% inhibition in pseudovirus assay at ~244 mcmol/L. Active against wild-type and VOCs including BA.5 and KP.3. Active in diluted human serum. Non-toxic to human cell lines. Did not block antibody binding to RBD.","methodology":"Designed peptides from four RBD regions. Tested ACE-2 binding, RBD competition, pseudovirus inhibition, activity in human serum, cytotoxicity, and antibody compatibility.","limitations":"Pseudovirus assay only, not live virus. High concentration needed (244 mcmol/L). No in vivo data. Peptide stability and delivery not addressed."},{"rthcId":"RPEP-13478","title":"The antibacterial activity and therapeutic potential of the amphibian-derived peptide TB_KKG6K.","authors":"Schöpf, Cristina; Knapp, Magdalena; Scheler, Jakob; Coraça-Huber, Débora C; Romanelli, Alessandra; Ladurner, Peter; Seybold, Anna C; Binder, Ulrike; Würzner, Reinhard; Marx, Florentine","year":2025,"journal":"mSphere, 10(6), e0101624","doi":"10.1128/msphere.01016-24","pmid":"40387366","tags":["antimicrobial-peptides","skin-dermatology"],"studyType":"laboratory study","evidenceStrength":"preliminary","keyFinding":"The frog-derived antimicrobial peptide analog TB_KKG6K killed drug-resistant Staphylococcus aureus at low concentrations by disrupting bacterial membranes. It was non-toxic in animal models and reduced bacterial load and inflammation in 3D human skin models.","whyItMatters":"MRSA and other drug-resistant skin infections need new treatments. This small peptide showed both killing power and safety in lab and tissue models, making it a strong candidate for topical skin treatments.","specificNumbers":"13-amino-acid peptide. Bactericidal at low micromolar concentrations. Mechanism: membrane permeabilization and depolarization. No toxicity in Galleria mellonella model. Significant bacterial load reduction in infected human epidermis equivalents.","methodology":"Tested antibacterial activity (MIC), membrane disruption mechanisms, toxicity in Galleria mellonella invertebrate model, and therapeutic efficacy in 3D human epidermis equivalents infected with S. aureus. Measured bacterial load and inflammatory response.","limitations":"In vitro and ex vivo models only. No human clinical data. Stability on real skin with sweat, enzymes, and microbiome not tested. Galleria mellonella is a limited toxicity model."},{"rthcId":"RPEP-13479","title":"Thyroid Response to Peripheral Endocrine Factors: Neuropeptide Y Influences Thyroid Function in the Reptile Podarcis siculus.","authors":"Sciarrillo, Rosaria; Lallo, Assunta; Carrella, Francesca; Gallicchio, Vito; Mileo, Aldo; Valvano, Benedetta Sgangarella; De Falco, Maria","year":2025,"journal":"International journal of molecular sciences, 26(23)","doi":"10.3390/ijms262311513","pmid":"41373667","tags":["neuroscience-neurological","hormones-endocrine"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Neuropeptide Y (NPY) activated the thyroid axis in lizards in a dose-dependent manner, increasing thyroid hormones T3 and T4 while decreasing TRH and TSH. NPY also increased hepatic T3 production through deiodinase activity.","whyItMatters":"This is the first clear evidence that NPY regulates thyroid function in reptiles, extending our understanding of this neuropeptide's metabolic roles across species.","specificNumbers":"Dose-dependent effects at 2 and 24 hours post-administration. Plasma TRH and TSH decreased. Plasma T3 and T4 increased. Thyroid follicular epithelium height increased dose-dependently. Hepatic T3 increased and T4 decreased (indicating deiodinase activity).","methodology":"NPY administered to Podarcis siculus lizards. Plasma TRH, TSH, T3, and T4 measured at 2 and 24 hours. Thyroid gland histology. Hepatic type II 5'-T4 outer ring deiodinase activity measured.","limitations":"Reptile study with limited sample details. Results may not translate to mammalian or human thyroid physiology. Short-term measurements only."},{"rthcId":"RPEP-13480","title":"Congestion and systemic inflammation in acute heart failure: correlations and prognostic role.","authors":"Scicchitano, Pietro; De Feo, Daniele; Iacoviello, Massimo; Albani, Stefano; Ricci, Gabriella; Livrieri, Anna; Campanella, Cosimo; Caldarola, Pasquale; Ciccone, Marco Matteo; Massari, Francesco","year":2025,"journal":"Frontiers in cardiovascular medicine, 12, 1695500","doi":"10.3389/fcvm.2025.1695500","pmid":"41333749","tags":["cardiovascular","immunology-inflammation"],"studyType":"prospective cohort study","evidenceStrength":"moderate","keyFinding":"In 314 patients with acute heart failure, both inflammation markers (hs-CRP and NLR) correlated with congestion markers and independently predicted 90-day mortality. An inflammation index combining both markers gave a hazard ratio of 2.3 for death.","whyItMatters":"Inflammation and fluid overload interact in acute heart failure. Measuring both together improves mortality prediction, which could help doctors identify the highest-risk patients early.","specificNumbers":"314 patients. hs-CRP at admission: 12.1 mg/L. NLR: 4.8. Both correlated with congestion markers (ePVS, HI, BUN/Cr, BNP). Inflammation index HR 2.3 for 90-day mortality. Congestion index HR 1.4. Combined C-index 0.72.","methodology":"Prospective enrollment of 314 acute heart failure patients. Measured hs-CRP, NLR, BNP, ePVS, hydration index, and BUN/Cr ratio at admission. Cox regression and combined inflammation/congestion indexes for 90-day mortality prediction.","limitations":"Single-center study. 90-day follow-up only. Observational design cannot prove causal relationships. Cut-offs for biomarker indexes need external validation."},{"rthcId":"RPEP-13481","title":"Nutritional deficiencies and muscle loss in adults with type 2 diabetes using GLP-1 receptor agonists: A retrospective observational study.","authors":"Scott Butsch, W; Sulo, Suela; Chang, Andrew T; Kim, Jeeyun A; Kerr, Kirk W; Williams, Dominique R; Hegazi, Refaat; Panchalingam, Thadchaigeni; Goates, Scott; Heymsfield, Steven B","year":2025,"journal":"Obesity pillars, 15, 100186","doi":"10.1016/j.obpill.2025.100186","pmid":"40584822","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13482","title":"Identification of cannabinoid-sensitive and -resistant oral bacteria.","authors":"Scott, David A; Lamont, Gwyneth J; Tan, Jinlian; Patel, Arjun P; Guffey, Jack T; Thomas, Scott C; Xu, Fangxi; Diamond, Gill; Saxena, Deepak","year":2025,"journal":"Frontiers in microbiology, 16, 1709243","doi":"10.3389/fmicb.2025.1709243","pmid":"41561022","tags":["antimicrobial-peptides","oral-dental-health"],"studyType":"laboratory study","evidenceStrength":"preliminary","keyFinding":"Cannabidiol (CBD) killed several oral bacteria linked to gum disease but other oral bacteria were completely resistant. Cathelicidin-mimicking peptoids sensitized resistant bacteria to CBD and also killed them directly.","whyItMatters":"Cannabis use is linked to worse gum disease. This study explains why: CBD kills some oral bacteria but not others, creating an imbalance. Antimicrobial peptoids could target the resistant bacteria that cannabis promotes.","specificNumbers":"CBD-sensitive: A. actinomycetemcomitans, F. nucleatum, P. gingivalis strains, S. mutans, S. gordonii, T. forsythia. CBD-resistant: C. gracilis, C. durum, H. parainfluenzae, Treponema species, V. parvula. Peptoids rendered CBD toxic to normally resistant spirochetes.","methodology":"In vivo microbiome analysis of marijuana users vs non-users with periodontitis. In vitro CBD susceptibility testing across oral bacteria panel. Screened cathelicidin-based peptoid library against T. denticola. Tested peptoid-CBD combination effects. Electron microscopy of treated bacteria.","limitations":"In vitro susceptibility testing. Clinical relevance of bacterial killing at tested concentrations is uncertain. No animal or human treatment studies. Peptoid safety and pharmacokinetics unknown."},{"rthcId":"RPEP-13483","title":"The societal implications of using glucagon-like peptide-1 receptor agonists for the treatment of obesity.","authors":"Scragg, Jadine; Koutoukidis, Dimitrios A; Dirksen, Carsten; Heitmann, Berit Lilienthal; Jebb, Susan A","year":2025,"journal":"Med (New York, N.Y.), 6(9), 100805","doi":"10.1016/j.medj.2025.100805","pmid":"40834863","tags":["glp1-receptor-agonists","weight-management","public-health"],"studyType":"perspective / commentary","evidenceStrength":"not applicable (commentary)","keyFinding":"GLP-1 receptor agonists achieve 15-25% weight loss in trials but face challenges including cost, adherence, weight regain after stopping, and potential to widen health inequalities. Prevention remains essential.","whyItMatters":"As GLP-1 drugs scale to millions of users, their societal impact goes beyond individual weight loss. Without equitable access and sustainable support systems, these drugs could worsen health disparities.","specificNumbers":"15-25% weight loss in clinical trials. Weight regain is marked after cessation. Limited adherence data outside clinical trials.","methodology":"Commentary reviewing clinical trial data, real-world adherence evidence, cost considerations, and equity implications of GLP-1RA rollout for obesity.","limitations":"Opinion/perspective piece. Does not present new data. May not capture all viewpoints on GLP-1RA policy issues."},{"rthcId":"RPEP-13484","title":"Comparing eptinezumab with onabotulinumtoxinA in the treatment of chronic migraine: a real-world evidence study.","authors":"Scuteri, Damiana; Pagliaro, Martina; Iannacchero, Rosario; Trimboli, Michele; Lawrence, Gary W; Bagetta, Giacinto; Corasaniti, Maria Tiziana","year":2025,"journal":"The journal of headache and pain, 26(1), 159","doi":"10.1186/s10194-025-02106-z","pmid":"40660133","tags":["neuroscience-neurological","pain-management","clinical-trials"],"studyType":"prospective observational study","evidenceStrength":"low-moderate","keyFinding":"Eptinezumab (anti-CGRP antibody) and onabotulinumtoxinA showed similar efficacy for chronic migraine at 3 and 6 months, with no significant differences in monthly migraine days, headache days, pain intensity, or disability scores.","whyItMatters":"Both treatments work for chronic migraine, but head-to-head data are scarce. This real-world comparison supports using onabotulinumtoxinA as an alternative or add-on to anti-CGRP antibodies.","specificNumbers":"40 chronic migraine patients refractory to standard treatments. 15 over age 50, 4 over 65. Both treatments reduced MMDs and MHDs at 3 and 6 months. No statistically significant differences for any primary or secondary endpoint. Both reduced rescue medication use.","methodology":"Prospective observational study of 40 chronic migraine patients in Italy. Compared eptinezumab vs onabotulinumtoxinA. Endpoints: monthly migraine days, headache days, rescue medication use, pain intensity, and MIDAS disability scores at 3 and 6 months. Two-way RM ANOVA with Bonferroni/Sidak correction.","limitations":"Small sample (40 patients). Not randomized. Real-world Italian setting with high medication overuse headache prevalence. Non-blinded comparison. Short follow-up."},{"rthcId":"RPEP-13485","title":"Epigenetics in migraine: the Junior Editorial Board Members' vision.","authors":"Scuteri, Damiana; Labastida-Ramirez, Alejandro; Rubio-Beltran, Eloisa; Vuralli, Doga; Onofri, Agnese","year":2025,"journal":"The journal of headache and pain, 27(1), 20","doi":"10.1186/s10194-025-02240-8","pmid":"41345551","tags":["neuroscience-neurological","pain-management"],"studyType":"systematic review","evidenceStrength":"low-moderate","keyFinding":"Epigenetic modifications (DNA methylation and microRNAs) play emerging roles in migraine chronification and treatment response. Changes in CGRP pathway genes, TRPV1/TRPA1, and estrogen receptor signaling may explain why some patients resist current therapies including anti-CGRP drugs.","whyItMatters":"40% of migraine patients on anti-CGRP therapy remain difficult to treat. Epigenetic markers could help predict who will respond to specific treatments and guide personalized migraine care.","specificNumbers":"40% of patients on anti-CGRP therapy remain difficult to treat. Altered DNA methylation found in genes for synaptic plasticity and estrogen receptor signaling. MicroRNA changes linked to migraine frequency. Gepant treatment reduced upregulated circulating miRNAs.","methodology":"Systematic review of PubMed, Scopus, and Web of Science from inception to October 2025. Focused on epigenetic mechanisms (DNA methylation, histone modification, miRNAs) in migraine pathogenesis and treatment response.","limitations":"Few studies available on epigenetics in migraine. Heterogeneous methodologies across studies. Epigenetic findings are associative, not necessarily causal. Small sample sizes in most original studies."},{"rthcId":"RPEP-13486","title":"Translational Impact of Genetics and Epigenetics of CGRP System on Chronic Migraine Treatment with Onabotulinumtoxin A and Other Biotech Drugs.","authors":"Scuteri, Damiana; Martelletti, Paolo","year":2025,"journal":"Toxins, 17(7)","doi":"10.3390/toxins17070355","pmid":"40711166","tags":["neuroscience-neurological","pain-management"],"studyType":"narrative review","evidenceStrength":"not applicable (review)","keyFinding":"Genetic variants and epigenetic modifications in the CGRP pathway may influence both migraine susceptibility and response to onabotulinumtoxin A and anti-CGRP monoclonal antibodies. This area remains poorly studied.","whyItMatters":"OnabotulinumtoxinA has been used for chronic migraine for over a decade, but predicting who will respond remains difficult. Genetic and epigenetic profiling of the CGRP pathway could improve patient selection.","specificNumbers":"OnabotulinumtoxinA FDA-approved 2010, now approved in 100 countries for 15 indications. Genetic variants studied: ACE, MTHFR, and CGRP pathway genes.","methodology":"Narrative review of genetic variants and epigenetic modifications affecting the CGRP signaling pathway in relation to migraine susceptibility and treatment response (onabotulinumtoxinA and anti-CGRP mAbs).","limitations":"Narrative review with limited primary evidence. Epigenetics of the CGRP pathway in migraine is poorly studied. Most genetic studies are small and underpowered."},{"rthcId":"RPEP-13487","title":"As Few as Three Months of Preoperative Semaglutide Exposure Prior to Total Knee Arthroplasty Is Associated With Reduced Postoperative Adverse Events in Patients Who Have Type II Diabetes.","authors":"Seddio, Anthony E; Vasudevan, Rajiv S; Gouzoulis, Michael J; Ansah-Twum, Jeremy K; Grauer, Jonathan N; Rubin, Lee E","year":2025,"journal":"The Journal of arthroplasty, 40(12), 3089-3096.e1","doi":"10.1016/j.arth.2025.08.003","pmid":"40784425","tags":["glp1-receptor-agonists","safety-tolerability","bone-joint-health"],"studyType":"retrospective database study","evidenceStrength":"low-moderate","keyFinding":"As few as 3 months of semaglutide before total knee replacement reduced both minor and severe postoperative complications in diabetic patients. Even less than 1 month of use lowered minor adverse events (OR 0.16). Severe event reduction became significant at 2-3 months (OR 0.25).","whyItMatters":"This is the first study to identify a minimum duration of semaglutide use needed for surgical benefit. A 3-month preoperative window is clinically actionable for surgical planning.","specificNumbers":"After matching: 745 (6-12 mo), 451 (3-6 mo), 210 (2-3 mo), 113 (1-2 mo), 91 (<1 mo) semaglutide patients. <1 month: MAE OR 0.16 (p<0.001). 2-3 months: SAE OR 0.25 (p<0.001). Consistent MAE reduction across all durations.","methodology":"Retrospective cohort from national database. T2DM patients undergoing TKA stratified by semaglutide exposure duration (5 groups). Each matched 1:4 with non-semaglutide controls. 90-day adverse events compared by multivariable logistic regression.","limitations":"Retrospective observational. Cannot prove causation. Database may not capture all confounders. Smallest groups (<1 month, 1-2 months) have limited sample sizes. No functional outcome data."},{"rthcId":"RPEP-13488","title":"Endoscopic and Open Carpal Tunnel Release in Patients With Type II Diabetes Mellitus: Influence of Preoperative Semaglutide Use on Postoperative Outcomes.","authors":"Seddio, Anthony E; Day, Wesley; Rancu, Albert L; Modrak, Maxwell; Joo, Peter Y; Grauer, Jonathan N","year":2025,"journal":"The Journal of hand surgery, 50(12), 1467-1475","doi":"10.1016/j.jhsa.2025.09.003","pmid":"41105066","tags":["glp1-receptor-agonists","safety-tolerability","bone-joint-health"],"studyType":"retrospective database study","evidenceStrength":"low-moderate","keyFinding":"Preoperative semaglutide use in diabetic patients undergoing carpal tunnel release was associated with lower odds of several complications including surgical site infection (69% lower for open surgery), wound dehiscence, and pneumonia. Reoperation rates were similar.","whyItMatters":"This extends the growing body of evidence that semaglutide may improve surgical outcomes in diabetic patients, even for relatively low-risk hand surgeries.","specificNumbers":"689 ECTR (1.2%) and 1,966 OCTR (0.8%) patients on semaglutide. After matching: 426 ECTR, 1,673 OCTR. OCTR semaglutide group: SSI OR 0.31, sepsis OR 0.61, wound dehiscence OR 0.25, pneumonia OR 0.26, UTI OR 0.33 (all p<0.001 range). Similar 2-year reoperation rates.","methodology":"Retrospective analysis of PearlDiver database. T2DM patients undergoing ECTR or OCTR. Semaglutide users (within 1 year pre-surgery) matched 1:4 with controls. 90-day complications by multivariable logistic regression. 2-year reoperation by Kaplan-Meier analysis.","limitations":"Retrospective database study. Cannot prove causation. Semaglutide users may be healthier or better-managed. Administrative coding may be inaccurate. No BMI or HbA1c matching."},{"rthcId":"RPEP-13489","title":"Improved total shoulder arthroplasty outcomes associated with semaglutide utilization in patients with type II diabetes: a promising new addition to preoperative optimization.","authors":"Seddio, Anthony E; Wilhelm, Christopher V; Gouzoulis, Michael J; Islam, Wasif; Vasudevan, Rajiv S; Halperin, Scott J; Rubin, Lee E; Medvecky, Michael J; Donohue, Kenneth W; Grauer, Jonathan N","year":2025,"journal":"JSES international, 9(3), 735-740","doi":"10.1016/j.jseint.2024.10.006","pmid":"40486798","tags":["glp1-receptor-agonists","safety-tolerability","bone-joint-health"],"studyType":"retrospective database study","evidenceStrength":"low-moderate","keyFinding":"Preoperative semaglutide in diabetic patients undergoing total shoulder replacement was associated with 75% lower surgical site infection, 68% lower cardiac events, 64% lower VTE, 75% lower pneumonia, and fewer other complications at 90 days.","whyItMatters":"Total shoulder replacement outcomes are worse in diabetic patients. This study adds shoulder surgery to the growing list of procedures where semaglutide may improve perioperative outcomes.","specificNumbers":"632 T2DM +semaglutide matched with 2,302 controls. SSI OR 0.25 (p=0.003), cardiac events OR 0.32 (p=0.003), VTE OR 0.36 (p=0.001), pneumonia OR 0.25 (p<0.001).","methodology":"Retrospective PearlDiver database analysis. T2DM patients undergoing anatomic or reverse TSA. Semaglutide users (within 1 year) matched 1:4 with controls on age, sex, ECI, diabetic complications, BMI, tobacco, insulin, and metformin. 90-day complications by univariable and multivariable analysis.","limitations":"Retrospective observational study. Cannot prove causation. Unmeasured confounders may exist. Database coding limitations. No functional shoulder outcomes reported."},{"rthcId":"RPEP-13490","title":"Lower Risk of Postoperative Complications and Rotator Cuff Retear Associated With Semaglutide Use in Patients with Type II Diabetes Mellitus Undergoing Arthroscopic Rotator Cuff Repair.","authors":"Seddio, Anthony E; Moran, Jay; Gouzoulis, Michael J; Garbis, Nickolas G; Salazar, Dane H; Grauer, Jonathan N; Jimenez, Andrew E","year":2025,"journal":"Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association, 41(2), 199-206","doi":"10.1016/j.arthro.2024.09.057","pmid":"39490542","tags":["glp1-receptor-agonists","safety-tolerability","bone-joint-health"],"studyType":"retrospective database study","evidenceStrength":"low-moderate","keyFinding":"Preoperative semaglutide in diabetic patients undergoing rotator cuff repair was associated with dramatically lower 90-day complications (AAE 11% vs 27.4%) and lower 2-year retear rates (12.5% vs 18.3%). Non-semaglutide patients had 3-4x higher odds of most complications.","whyItMatters":"This is the first study to show semaglutide may reduce rotator cuff retear rates, not just perioperative complications. Tendon healing improvement would be a novel benefit beyond infection reduction.","specificNumbers":"1,094 +semaglutide, 4,110 -semaglutide after matching. AAE 11.0% vs 27.4%. SAE 3.5% vs 10.5%. MAE 8.5% vs 22.0%. -Semaglutide ORs: AAE 3.65, SAE 3.62, SSI 2.22, VTE 3.10, sepsis 3.87, cardiac 3.96 (all p<0.001). 2-year retear: 12.5% vs 18.3% (p<0.001).","methodology":"PearlDiver database. T2DM patients undergoing primary ARCR. Semaglutide users matched 1:4 with controls on demographics, comorbidities, and diabetes medications. 90-day complications by multivariable logistic regression. 2-year retear by Kaplan-Meier and log-rank test.","limitations":"Retrospective observational. Cannot prove causation. Retear defined by billing codes, not MRI confirmation. Semaglutide users may differ in unmeasured ways. No functional outcome data."},{"rthcId":"RPEP-13491","title":"Reduced 90-Day Cardiovascular and Infectious Complications After Open Reduction Internal Fixation of Ankle Fractures in Type II Diabetic Patients Using Semaglutide Preoperatively.","authors":"Seddio, Anthony E; Vasudevan, Rajiv S; Jonnalagadda, Anshu; Slevin, John P; Grauer, Jonathan N; Fram, Brianna R","year":2025,"journal":"The Journal of the American Academy of Orthopaedic Surgeons, 33(16), e971-e978","doi":"10.5435/JAAOS-D-25-00439","pmid":"40549942","tags":["glp1-receptor-agonists","safety-tolerability","bone-joint-health"],"studyType":"retrospective database study","evidenceStrength":"low-moderate","keyFinding":"Preoperative semaglutide use in diabetic patients undergoing ankle fracture surgery reduced 90-day odds of DVT (76%), MI (66%), surgical site infection (70%), sepsis (62%), pneumonia (73%), UTI (73%), wound dehiscence (69%), and ER visits (55%).","whyItMatters":"Ankle fracture surgery in diabetic patients has high complication rates. This is the first study suggesting semaglutide may improve outcomes in this trauma surgery setting.","specificNumbers":"2,700 semaglutide users (2.73%) identified. 804 matched pairs analyzed. ORs vs. controls: DVT 0.24, MI 0.34, SSI 0.30, sepsis 0.38, pneumonia 0.27, UTI 0.27, wound dehiscence 0.31, ED visit 0.45 (all p<0.001).","methodology":"Retrospective analysis of PearlDiver database (2010-Q1 2023). T2DM patients undergoing ankle fracture ORIF. Semaglutide users matched with controls on age, sex, BMI, comorbidities, insulin/metformin/SGLT2i use, and insurance. 90-day outcomes by multivariable logistic regression with Bonferroni correction.","limitations":"Retrospective database study. Cannot establish causation. Selection bias likely (semaglutide users may differ in unmeasured ways). No fracture severity data. Acute trauma setting differs from elective surgery."},{"rthcId":"RPEP-13492","title":"Semaglutide utilization associated with reduced 90-day postoperative complications following single-level posterior lumbar fusion for patients with type II diabetes.","authors":"Seddio, Anthony E; Gouzoulis, Michael J; Vasudevan, Rajiv S; Dhodapkar, Meera M; Jabbouri, Sahir S; Varthi, Arya G; Rubio, Daniel R; Grauer, Jonathan N","year":2025,"journal":"The spine journal : official journal of the North American Spine Society, 25(3), 485-493","doi":"10.1016/j.spinee.2024.10.011","pmid":"39491749","tags":["glp1-receptor-agonists","safety-tolerability","bone-joint-health"],"studyType":"retrospective database study","evidenceStrength":"low-moderate","keyFinding":"Preoperative semaglutide reduced 90-day adverse events after single-level lumbar spine fusion in diabetic patients. Benefits were seen in both insulin-using (SAE OR 0.43, MAE OR 0.34) and non-insulin-using (MAE OR 0.45) groups. Hospital readmission rates were similar.","whyItMatters":"Spine surgery in diabetic patients carries significant complication risk. This extends semaglutide's apparent perioperative benefit to another major surgical procedure.","specificNumbers":"T2DM-insulin: 227 semaglutide (0.73%), matched to 191. T2DM+insulin: 244 semaglutide (2.17%), matched to 148. T2DM-insulin +sema: AAE OR 0.43, MAE OR 0.45, ED visits OR 0.34 (p<0.001). T2DM+insulin +sema: AAE OR 0.40, SAE OR 0.43, MAE OR 0.34, ED visits OR 0.26 (p<0.001). Readmissions similar in both.","methodology":"Retrospective PearlDiver database analysis (2010-Q2 2022). T2DM patients undergoing single-level PLF stratified by insulin use. Semaglutide users matched 1:4 with controls on age, sex, ECI, obesity, tobacco, metformin, and SGLT2i use. 90-day adverse events by multivariable analysis with Bonferroni correction.","limitations":"Retrospective observational. Cannot prove causation. Small semaglutide groups after matching (191 and 148). Database coding limitations. No spine-specific outcomes (fusion rate, functional scores)."},{"rthcId":"RPEP-13493","title":"Evolving Role of Double and Triple Therapy With GLP-1 Receptor Agonists in Obesity and Cardiovascular Disease.","authors":"Sedrak, Phelopater; Verma, Raj; Verma, Meena; Connelly, Kim A","year":2025,"journal":"The Canadian journal of cardiology, 41(9), 1809-1822","doi":"10.1016/j.cjca.2025.03.037","pmid":"40311673","tags":["glp1-receptor-agonists","cardiovascular","weight-management"],"studyType":"narrative review","evidenceStrength":"not applicable (review)","keyFinding":"This review covers the evolution from single GLP-1RAs to dual GLP-1/GIP agonists and triple GLP-1/GIP/glucagon agonists, with expanding evidence for atherosclerosis and heart failure benefits beyond glucose and weight control.","whyItMatters":"The next generation of incretin therapies may provide even greater cardiometabolic benefits. Understanding the pipeline helps clinicians anticipate upcoming treatment options.","specificNumbers":"Not specified (review covering multiple drug classes and trials)","methodology":"Narrative review of GLP-1RA evolution, dual and triple agonist development, and completed/ongoing cardiovascular trials.","limitations":"Narrative review, not systematic. May not capture all ongoing trials. Triple agonist clinical data are still early-stage."},{"rthcId":"RPEP-13494","title":"Expectations and Outcomes From Glucagon-Like Peptide-1 Receptor Agonists As Adjunct Treatment for Type 1 Diabetes - Case Presentations.","authors":"Seetharaman, Sujatha; Cengiz, Eda","year":2025,"journal":"Journal of diabetes science and technology, 19(2), 304-310","doi":"10.1177/19322968241305641","pmid":"39707844","tags":["glp1-receptor-agonists","metabolic-disorders"],"studyType":"case series","evidenceStrength":"low","keyFinding":"GLP-1 RAs (semaglutide and tirzepatide) used off-label in adolescents and young adults with type 1 diabetes improved glycemic control and reduced weight in most patients. One patient developed an eating disorder. Insurance and supply issues disrupted treatment.","whyItMatters":"Real-world data on GLP-1 drugs in young T1D patients is scarce. This case series highlights both benefits and unique risks in this population, including eating disorder development.","specificNumbers":"Not specified (case series of adolescents and young adults at a single center). Most had obesity. No DKA episodes reported. One eating disorder case.","methodology":"Single-center case series of GLP-1RA use as adjunct to insulin in adolescents and young adults with T1D. Focused on glycemic parameters, weight, side effects, and practical issues.","limitations":"Case series without controls. Single center. Small and unspecified sample size. No long-term follow-up. Selection bias likely."},{"rthcId":"RPEP-13495","title":"The Promise of Adjunct Medications in Improving Type 1 Diabetes Outcomes: Glucagon-Like Peptide Receptor Agonists.","authors":"Seetharaman, Sujatha; Cengiz, Eda","year":2025,"journal":"Journal of diabetes science and technology, 19(2), 311-320","doi":"10.1177/19322968241309896","pmid":"40022528","tags":["glp1-receptor-agonists","metabolic-disorders"],"studyType":"narrative review","evidenceStrength":"not applicable (review)","keyFinding":"GLP-1 receptor agonists used off-label in type 1 diabetes show improvements in HbA1c, weight loss, and reduced insulin doses. GI side effects are common, and some studies reported hypoglycemia and ketosis risks.","whyItMatters":"Many people with type 1 diabetes also have obesity and insulin resistance. GLP-1RAs could fill a major treatment gap if safety concerns are managed, but they are not yet approved for T1D.","specificNumbers":"Improvements in HbA1c, reduced insulin doses, significant weight loss reported across studies. GI side effects common. Some reported hypoglycemia, hyperglycemia, and ketosis.","methodology":"Review of published studies (up to May 2024) from PubMed and Scopus on GLP-1RAs in T1D, plus cardiorenal outcomes data from T2D and obesity studies.","limitations":"No GLP-1RA is approved for T1D. Studies are mostly small and short-term. Ketosis risk is a serious concern. Long-term safety data in T1D are lacking."},{"rthcId":"RPEP-13496","title":"Next-generation antifungal peptide discovery: the synergy of artificial intelligence and omics technologies.","authors":"Seiad Ahmadnezhad, Reihaneh; Shams-Ghahfarokhi, Masoomeh; Jamzivar, Fatemehsadat; Eslamifar, Ali; Sohrabi, Aria; Razzaghi-Abyaneh, Mehdi","year":2025,"journal":"World journal of microbiology & biotechnology, 41(12), 456","doi":"10.1007/s11274-025-04662-7","pmid":"41251968","tags":["antimicrobial-peptides","drug-discovery-screening"],"studyType":"narrative review","evidenceStrength":"not applicable (review)","keyFinding":"AI tools (machine learning, deep learning, NLP) combined with omics and CRISPR technologies can accelerate antifungal peptide discovery, design, and production. Current challenges include limited training data, model interpretability, delivery systems, and clinical translation.","whyItMatters":"Fungal infections and antifungal resistance are growing threats. AI-driven peptide discovery could dramatically speed up development of new antifungals with better efficacy and lower resistance potential.","specificNumbers":"Not specified (technology review covering AI approaches, omics, and CRISPR-Cas9 for AFP development)","methodology":"Narrative review covering machine learning, deep learning, NLP, omics technologies, CRISPR-Cas9, transfer learning, explainable AI, and genetic algorithms applied to antifungal peptide discovery.","limitations":"Technology review without clinical data. AI models face challenges with limited training data and interpretability. Gap between computational prediction and clinical efficacy remains large."},{"rthcId":"RPEP-13497","title":"Machine Learning Guided Video Analysis Identifies Sound-Evoked Pain Behaviors from Facial Grimace and Body Cues in Mice.","authors":"Seicol, Benjamin J; Valles, Amelie; Kohler, Anna; Glowatzki, Elisabeth; Wood, Megan B","year":2025,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2025.09.30.679579","pmid":"41256403","tags":["neuroscience-neurological","pain-management"],"studyType":"animal study (methods development)","evidenceStrength":"preliminary","keyFinding":"A machine learning-based video analysis system measured sound-evoked pain in mice by combining facial grimace and body posture. CGRP-induced migraine validated the pain threshold. Intense sounds exceeded this threshold, and the response was absent in mice lacking cochlear function.","whyItMatters":"Auditory pain (painful hearing) is poorly understood because there was no objective way to measure it in animals. This automated tool opens the door to studying the mechanisms of sound-induced pain.","specificNumbers":"Pain quantified from facial grimace (deep neural network) and body posture from single-camera video. CGRP injection used as positive control for pain threshold. TMIE-knockout mice (no cochlear function) showed no response.","methodology":"Deep learning analysis of mouse video during sound exposure. Trained on established facial action units. Validated with CGRP-induced migraine model. Tested in wild-type and TMIE-knockout mice at various sound intensities.","limitations":"Mouse model. CGRP-induced migraine is a model, not identical to human migraine. Automated scoring may miss subtle pain behaviors. Preprint (not peer reviewed)."},{"rthcId":"RPEP-13498","title":"Treat to target in weight management with semaglutide: Real-world evidence from an eHealth clinic.","authors":"Seier, Søren; Stamp-Larsen, Kine; Jensen, Simon Birk Kjær; Torekov, Signe Sørensen; Gudbergsen, Henrik","year":2025,"journal":"Diabetes, obesity & metabolism, 27(12), 6979-6987","doi":"10.1111/dom.70096","pmid":"40903862","tags":["glp1-receptor-agonists","weight-management"],"studyType":"retrospective cohort study","evidenceStrength":"moderate","keyFinding":"A digital weight management program combining personalized semaglutide dosing with behavioral therapy achieved 16.7% weight loss at 64 weeks with a mean dose of only 1.08 mg/week. 98% achieved at least 5% weight loss and 82% achieved at least 10%.","whyItMatters":"Real-world weight loss matched clinical trial results despite using lower semaglutide doses, suggesting personalized dosing with behavioral support can optimize outcomes while reducing drug costs.","specificNumbers":"2,694 participants. 78% women. Mean BMI 34.3. At week 64: 465 remaining. Mean weight loss 16.7% (95% CI -17.4 to -16.0). Mean semaglutide dose 1.08 mg/week (SD 0.54). 98% achieved ≥5% loss, 82% ≥10%.","methodology":"Retrospective analysis of Danish participants in a digital weight loss program (Embla app) from January 2022 to September 2024. Individualized semaglutide dosing with evidence-based behavioral therapy. All data collected via app.","limitations":"Retrospective. High attrition (2,694 started, 465 at week 64). Completers bias likely inflates results. No control group. Danish population may not generalize globally."},{"rthcId":"RPEP-13499","title":"Effects of GLP-1 agonists on 10-year cardiovascular risk reduction in primary prevention: A 44-week open label prospective study.","authors":"Seijas-Amigo, José; Salgado-Barreira, Ángel; Castelo-Dominguez, Rosana; Pérez-Álvarez, María Teresa; Ponce-Piñón, Belén; Fernández-Silva, Marlén; Rodríguez-Barreiro, Marta; Pereira-Pía, Mercedes; Iglesias-Moreno, Jose Manuel; Gago-García, Mar; Montáns-García, Raquel; Fernandez-Perez, Agustina; Fraga-Gayoso, Dolores; Fernandez-Montenegro, Montse; Riveiro-Barciela, Beatriz; Rilla-Villar, Natalia; Cardeso-Paredes, Begoña; Ribeiro-Ferreiro, Marta; Rodriguez-Penas, Diego; Cordero, Alberto; Rodríguez-Mañero, Moisés; González-Juanatey, José R","year":2025,"journal":"Diabetes & metabolic syndrome, 19(9), 103312","doi":"10.1016/j.dsx.2025.103312","pmid":"41129847","tags":["glp1-receptor-agonists","cardiovascular","clinical-trials"],"studyType":"prospective open-label study","evidenceStrength":"low-moderate","keyFinding":"GLP-1 receptor agonists reduced estimated 10-year cardiovascular risk by 13.45% (3.28 percentage points) over 44 weeks in primary prevention T2DM patients with obesity. Subcutaneous semaglutide produced the greatest weight loss (-8.1 kg).","whyItMatters":"Shows that GLP-1RAs reduce estimated cardiovascular risk in primary prevention, supporting their early use in high-risk diabetic patients before a cardiovascular event occurs.","specificNumbers":"135 patients, 105 in primary prevention cohort. 10-year CVR decreased by 3.28 percentage points (13.45% relative reduction, p<0.001). SC semaglutide: -8.1 kg. Oral semaglutide: -6.5 kg. Dulaglutide: -5.6 kg. HbA1c: 8.1% to 6.6%. FPG decreased 45.8 mg/dL (both p<0.001).","methodology":"44-week prospective, non-randomized study across 13 healthcare centers. Primary endpoint: change in 10-year CVR by AHA ASCVD Risk Estimator Plus. Secondary: weight, HbA1c, FPG, lipids. Various GLP-1RAs used. NCT05136287.","limitations":"Non-randomized, open-label. No control group. Uses estimated cardiovascular risk, not actual events. Mixed GLP-1RA types. Relatively short follow-up."},{"rthcId":"RPEP-13500","title":"Glucagon-like Peptide-1 Receptor Agonists Are Associated With a Lower Risk of Peptic Ulcer Disease: A Nationwide Cohort Study.","authors":"Seika, Philippa; Chang, Jocelyn; Hong, Su Min; Ballou, Sarah; Rangan, Vikram; Ramprasad, Chethan; Iturrino, Johanna; Denecke, Christian; Lembo, Anthony; Nee, Judy; Kulkarni, Subhash; Pasricha, Trisha","year":2025,"journal":"Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association","doi":"10.1016/j.cgh.2025.08.015","pmid":"40865627","tags":["glp1-receptor-agonists","liver-gi","safety-tolerability"],"studyType":"retrospective cohort study","evidenceStrength":"moderate","keyFinding":"GLP-1RA use in type 2 diabetes patients was associated with 44% lower odds of peptic ulcer disease. In a propensity-matched subgroup, switching to GLP-1RA as second-line therapy reduced peptic ulcer hazard by 56% compared to switching to insulin.","whyItMatters":"This is the first large study suggesting GLP-1RAs protect against peptic ulcers in diabetic patients. If confirmed, this adds to their growing list of benefits beyond blood sugar control.","specificNumbers":"66,102 T2DM patients in primary analysis. GLP-1RA adjusted OR for PUD: 0.56 (95% CI 0.45-0.71, p<0.001). Subgroup: 1,270 new GLP-1RA users vs 2,043 new insulin users. GLP-1RA adjusted HR: 0.44 (95% CI 0.30-0.63, p<0.001). NSAID HR 2.39, steroid HR 1.84.","methodology":"Nationwide retrospective study using All of Us NIH database. Primary analysis: time-dependent GLP-1RA use with adjusted logistic regression. Subgroup: propensity-weighted time-varying Cox model for new GLP-1RA vs new insulin users, accounting for competing risks of death and gastrectomy.","limitations":"Retrospective observational. Cannot prove causation. H. pylori status not captured. PUD diagnosis based on coding, not endoscopy. Short duration of some GLP-1RA exposures."},{"rthcId":"RPEP-13501","title":"Predicting Toxicity of Insect Venom-Derived Antimicrobial Peptides Using MD Simulations: A Comparative Study of Multi-Component and Realistic Mammalian Membrane Models.","authors":"Sekar, P Chandra; Gawde, Ulka; Kumar, Chandan; Idicula-Thomas, Susan","year":2025,"journal":"The Journal of membrane biology, 258(6), 505-518","doi":"10.1007/s00232-025-00363-2","pmid":"41108400","tags":["antimicrobial-peptides","drug-discovery-screening"],"studyType":"computational study","evidenceStrength":"preliminary","keyFinding":"Molecular dynamics simulations using realistic mammalian membrane models predicted toxicity of insect venom antimicrobial peptides with 90% accuracy. A widely used simpler membrane model performed poorly for toxicity prediction.","whyItMatters":"Testing peptide toxicity in the lab is expensive and slow. Computer simulations could pre-screen thousands of candidates, but only if the right membrane model is used.","specificNumbers":"16 toxic and 14 non-toxic AMP analogs from 5 insect families (anoplin, polybia, halictine, hyline, macropin). 25 microseconds total simulation time. 500 ns per peptide. RMSD analysis in last 100 ns achieved 90% accuracy with realistic membrane model.","methodology":"All-atom molecular dynamics simulations (500 ns each, 30 peptides) using two mammalian membrane models with different lipid compositions. Analyzed RMSD, structural stability, and membrane permeability. Compared predictions to experimental toxicity data.","limitations":"Computational predictions only. 90% accuracy means 10% error rate. Limited to five insect AMP families. Simulation conditions may not capture all factors affecting in vivo toxicity."},{"rthcId":"RPEP-13502","title":"Semaglutide-Associated Ischemic Colitis in a Patient Without Traditional Risk Factors: A Case Report.","authors":"Sekhon, Sommer; Bacon, John; Kahlon, Ibaadat Sukhmanii","year":2025,"journal":"Cureus, 17(2), e78832","doi":"10.7759/cureus.78832","pmid":"40084311","tags":["glp1-receptor-agonists","liver-gi","safety-tolerability"],"studyType":"case report","evidenceStrength":"low","keyFinding":"A 43-year-old woman without traditional risk factors developed ischemic colitis while on semaglutide. Symptoms resolved after stopping the medication and did not recur for several months.","whyItMatters":"Ischemic colitis is a rare but serious GI complication not typically associated with GLP-1 drugs. Clinicians should consider medication-induced colitis in semaglutide users with persistent abdominal symptoms.","specificNumbers":"43-year-old female. No traditional ischemic colitis risk factors. Initially misdiagnosed as infectious colitis. Colonoscopy confirmed ischemic colitis. Symptoms resolved after semaglutide discontinuation.","methodology":"Single case report with clinical documentation, imaging, colonoscopy, and follow-up after drug discontinuation.","limitations":"Single case. Temporal association does not prove causation. Ischemic colitis has many potential causes. No rechallenge performed."},{"rthcId":"RPEP-13503","title":"Neprilysin 2 catalyses the degradation of natriuretic peptides despite sacubitrilat Inhibition.","authors":"Selezneva, Elizaveta M; Feygina, Evgeniya E; Ageeva, Liudmila V; Rozov, Fedor N; Kopylova, Irina V; Altshuler, Evgeny P; Semenov, Alexander G","year":2025,"journal":"Scientific reports, 15(1), 27401","doi":"10.1038/s41598-025-10166-z","pmid":"40721616","tags":["cardiovascular","drug-discovery-screening"],"studyType":"laboratory study","evidenceStrength":"preliminary","keyFinding":"Neprilysin 2 (NEP2), a close relative of neprilysin, degrades natriuretic peptides ANP and BNP but is NOT blocked by sacubitrilat, the active form of the heart failure drug sacubitril. NEP2 is expressed in heart cells and blood vessel cells.","whyItMatters":"Heart failure patients take sacubitril to preserve natriuretic peptides. If NEP2 continues to break them down despite treatment, it could limit the drug's effectiveness. This reveals a potential therapeutic gap.","specificNumbers":"NEP2 and NEP mRNA detected in cardiomyocytes and endothelial cells. NEP2 cleaved ANP and BNP. NEP2 was insensitive to sacubitrilat. NEP2 (but not NEP) cleaved proBNP to truncated form (amino acids 5-32).","methodology":"RT-PCR for NEP and NEP2 expression in cardiovascular cells. In vitro cleavage assays using recombinant NEP and NEP2 soluble domains. Sandwich immunoassays with antibodies specific for proteolytic epitopes. Tested sacubitrilat inhibition.","limitations":"In vitro study. NEP2 protein expression and activity in vivo not confirmed. Relevance to clinical heart failure outcomes is theoretical. Studied concentrations may not reflect physiological conditions."},{"rthcId":"RPEP-13504","title":"Liraglutide mitigates dexamethasone-induced fatty acid synthase (FASN) and the cluster of differentiation36 (CD36) expression: a potential treatment for glucocorticoid-induced non-alcoholic fatty liver disease (NAFLD).","authors":"Selim, Dahshan Hassan; Mokhlis, Hamada Ahmed; Elsayed, Abdelrahman M; Shatat, Abdel-Aziz S; Salama, Salama Abdou; Ismail, Raed Shahat","year":2025,"journal":"Naunyn-Schmiedeberg's archives of pharmacology, 398(7), 8567-8585","doi":"10.1007/s00210-025-03789-6","pmid":"39820544","tags":["glp1-receptor-agonists","liver-gi"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Liraglutide reversed dexamethasone-induced fatty liver disease in animals by activating AMPK and reducing expression of FASN and CD36, two key genes in fat accumulation. Dexamethasone directly upregulates these genes through glucocorticoid response elements in their promoters.","whyItMatters":"Steroid medications commonly cause fatty liver. Understanding the mechanism (FASN and CD36 upregulation via glucocorticoid response elements) and showing liraglutide can reverse it provides a potential treatment strategy for steroid-induced liver disease.","specificNumbers":"DXM decreased p-AMPK; LG upregulated it. DXM increased FASN and CD36 expression (mRNA, protein, and immunohistochemistry). LG reversed both in a dose-dependent manner. Promoter analysis revealed multiple GRE in FASN and CD36.","methodology":"Animal model of NAFLD induced by high-fat diet and dexamethasone. Histopathology, liver enzyme levels, computational GRE analysis, RT-qPCR, western blot, and immunohistochemistry for FASN, CD36, and p-AMPK. Liraglutide tested at multiple doses.","limitations":"Animal study. Dexamethasone-induced NAFLD may differ from other NAFLD causes. Dose-response in animals may not translate to humans. Computational GRE analysis is predictive, not confirmatory."},{"rthcId":"RPEP-13505","title":"Designing highly tunable nanostructured peptide hydrogels using differential thermal histories to achieve variable cellular responses.","authors":"Sen, Sourav; Mohanty, Sweta; Roy, Sangita","year":2025,"journal":"Nanoscale, 17(7), 3983-3998","doi":"10.1039/d4nr04085f","pmid":"39760138","tags":["regenerative-medicine","peptide-manufacturing"],"studyType":"laboratory study","evidenceStrength":"preliminary","keyFinding":"A single peptide gelator formed diverse nanostructures with different properties simply by changing the gelation temperature. Higher temperatures created dense fiber networks with stronger gels and better cell adhesion, comparable to collagen.","whyItMatters":"Getting different materials from one peptide by just changing temperature is a simple, powerful approach for tissue engineering. It eliminates the need to design different peptides for different applications.","specificNumbers":"Gelation temperatures: 40-90°C. Higher temperature (70-90°C): dense, entangled networks, long fibers, strong gels, good cell adhesion. Lower temperature (40-60°C): less entangled, short fibers, weak gels, poor cell adhesion. Thermoreversible. Comparable to collagen gel for cell adhesion.","methodology":"Varied gelation induction temperature (40-90°C) for a single peptide gelator. Characterized nanostructure, mechanical properties, and thermoreversibility. Compared to collagen for cell adhesion and survival in culture.","limitations":"In vitro study. One peptide gelator tested. Cell adhesion studies are short-term. No in vivo biocompatibility data. Temperature control during clinical application may be challenging."},{"rthcId":"RPEP-13506","title":"Designing Short Cardin-Motif Peptide and Biopolymer-Based Multicomponent Hydrogels for Developing Advanced Composite Scaffolds for Improving Cellular Behavior.","authors":"Sen, Sourav; Kumar, Rakesh; Tomar, Rahul Singh; Roy, Sangita","year":2025,"journal":"Macromolecular bioscience, 25(5), e2400555","doi":"10.1002/mabi.202400555","pmid":"39838741","tags":["regenerative-medicine","peptide-manufacturing"],"studyType":"laboratory study","evidenceStrength":"preliminary","keyFinding":"Combining a cationic Cardin-motif peptide with cellulose nanofibers created composite scaffolds where different mixing ratios produced different cellular responses. A 10:1 ratio supported cell growth comparable to Matrigel in 3D culture.","whyItMatters":"The peptide alone could not form a gel at body conditions. Combining it with cellulose nanofibers created tunable scaffolds that could replace expensive Matrigel for tissue engineering applications.","specificNumbers":"10:1 (w/w) CNF:peptide ratio optimal for cell survival and proliferation. 3D culture performance comparable to Matrigel. Different mixing ratios modulated surface charge, functionality, and mechanical properties.","methodology":"Mixed cellulose nanofibers (CNF) with cationic Cardin-motif peptide at different ratios. Characterized mechanical properties and surface charge. Tested cell survival and proliferation in 2D and 3D culture conditions. Compared to Matrigel.","limitations":"In vitro cell culture only. No animal testing. Long-term stability and biocompatibility in vivo unknown. Only one peptide tested. Matrigel comparison is a high bar but limited to proliferation."},{"rthcId":"RPEP-13507","title":"Evolving incretin-based therapies in Japan: optimizing treatment strategies for diverse clinical and socioeconomical profiles in type 2 diabetes.","authors":"Seno, Yohei; Ikeguchi, Eri; Yabe, Daisuke","year":2025,"journal":"Diabetology international, 16(3), 457-468","doi":"10.1007/s13340-025-00818-w","pmid":"40607140","tags":["glp1-receptor-agonists","metabolic-disorders","aging-longevity"],"studyType":"narrative review","evidenceStrength":"not applicable (review)","keyFinding":"In Japan, DPP-4 inhibitors remain the backbone for older, non-obese diabetic patients, while GLP-1RAs serve younger obese patients. Tirzepatide's 2023 introduction showed superior glucose-lowering and weight reduction in both trials and Japanese real-world settings.","whyItMatters":"Japan's diabetic population differs from Western populations (older, leaner). This review helps clinicians understand how to select incretin-based therapies for Japan's unique patient profiles.","specificNumbers":"Over 70% of Japanese diabetic patients are aged 65+. Tirzepatide introduced in Japan in 2023. Japanese Diabetes Society safety guidelines referenced.","methodology":"Narrative review of incretin-based therapy use in Japan, including DPP-4 inhibitors, GLP-1RAs, and tirzepatide. Covers clinical trials, real-world Japanese data, and safety guidelines.","limitations":"Japan-focused review. Findings may not apply to other populations. Narrative format may not capture all evidence. Long-term tirzepatide data in Japan are limited."},{"rthcId":"RPEP-13508","title":"Patient Preferences for Self-Injectable Preventive Treatment for Migraine: A Multi-country Discrete Choice Experiment.","authors":"Seo, Jaein; Thomas, Caitlin; Tervonen, Tommi; Krucien, Nicolas; Ford, Janet H; Stauffer, Virginia L; Nicholson, Robert A; Duffy, Kevin Harrison; Tockhorn-Heidenreich, Antje","year":2025,"journal":"Neurology and therapy, 14(5), 2033-2051","doi":"10.1007/s40120-025-00801-2","pmid":"40753326","tags":["neuroscience-neurological","pain-management"],"studyType":"discrete choice experiment (survey)","evidenceStrength":"low-moderate","keyFinding":"Migraine patients strongly preferred self-injectable CGRP antibody autoinjectors over oral non-CGRP medications (86.3% of choices). Among autoinjectors, the most important attributes were shorter injection duration and auto-retractable needles.","whyItMatters":"Understanding patient preferences helps manufacturers design better devices and helps doctors have informed conversations about treatment options for migraine prevention.","specificNumbers":"1,067 participants (US, UK, Germany). 51.3% episodic migraine, 52.6% female, median age 40. Autoinjectors chosen 86.3% of the time. Top attribute: injection duration (RAI 37.0%), auto-retractable needle (30.8%), room temperature storage (15.2%), no pinching (12.5%). Galcanezumab-like profile: PCP 44.6% vs erenumab 28.8% vs fremanezumab 26.6%.","methodology":"Online discrete choice experiment in adults with episodic or chronic migraine from US, UK, and Germany. 12 choice tasks per participant. Three options per task (two autoinjectors, one oral). Seven autoinjector attributes. Error-component logit model analysis.","limitations":"Hypothetical choices may not reflect real-world decisions. Cost not included as an attribute. Self-selected online sample. Assumed equal efficacy across options. Does not include oral CGRP antagonists (gepants) as a comparator."},{"rthcId":"RPEP-13509","title":"Somatosensory neurons respond heterogeneously to a conditioning lesion.","authors":"Seo, Jeong W; Balog, Brian M; Pinkevitch, Margaret; Niemi, Jon P; Patru, Marius; Paranjape, Sanika; Zigmond, Richard E","year":2025,"journal":"Experimental neurology, 392, 115342","doi":"10.1016/j.expneurol.2025.115342","pmid":"40494479","tags":["neuroscience-neurological","regenerative-medicine"],"studyType":"animal study (basic neuroscience)","evidenceStrength":"preliminary","keyFinding":"Different types of sensory neurons respond differently to nerve injury conditioning. CGRP-positive pain neurons inherently cannot boost their regrowth after a prior injury. IB4-binding neurons, despite previous reports, actually can. TrkC+ and MrgD+ neurons also show this conditioning response.","whyItMatters":"Understanding which nerve cell types can regenerate after injury could lead to targeted therapies for nerve repair. The finding that CGRP neurons inherently lack this ability explains why pain nerve regeneration is limited.","specificNumbers":"CGRP+ neurons: no conditioning lesion response (confirmed by genetic reporter). IB4+/MrgD neurons: do show CLR (correcting previous reports). TrkC+ neurons: show CLR. About half of L3-L5 DRG neurons project into the sciatic nerve.","methodology":"Used genetic reporter mice (CGRP-cre and MrgD-cre) to track neuron identity after axotomy. Cultured DRG neurons with and without prior in vivo sciatic nerve conditioning lesion. Measured axonal growth in culture.","limitations":"Mouse study. In vitro growth may not reflect in vivo regeneration. Genetic reporters mark specific subpopulations; some overlap may exist. Functional recovery not assessed."},{"rthcId":"RPEP-13510","title":"Protein and Peptide in Cancer Research: From Biomarker to Biotherapeutics.","authors":"Seo, Joo Hyeong; Shin, Seung Hoon; Woo, Hye Rin; An, Yu Rim; Youn, A Hyun; Kim, Song Yeon; Ki, Mi-Ran; Pack, Seung Pil","year":2025,"journal":"Cancers, 17(18)","doi":"10.3390/cancers17183031","pmid":"41008874","tags":["cancer-oncology","drug-delivery-systems"],"studyType":"comprehensive review","evidenceStrength":"not applicable (review)","keyFinding":"This review covers proteins and peptides in cancer from biomarkers (PSA, CA125, HER2, AFP) to therapeutics (antibodies, checkpoint inhibitors, anticancer peptides) to advanced delivery systems (nanoparticle-peptide complexes). Emerging AI and synthetic biology tools are addressing peptide stability and delivery challenges.","whyItMatters":"Peptides offer high target specificity for cancer treatment but face stability and delivery barriers. This review maps the full landscape from diagnosis to therapy to next-generation technologies.","specificNumbers":"Diagnostic markers discussed: PSA, CA125, HER2, AFP. Techniques: ELISA, mass spectrometry, CyTOF. Therapeutic approaches: monoclonal antibodies, checkpoint inhibitors, anticancer peptides, nanoparticle-peptide delivery systems.","methodology":"Comprehensive review of published literature on protein and peptide applications in cancer diagnosis, treatment, and emerging technologies.","limitations":"Broad review covering many topics at survey depth. May not capture the most recent developments in rapidly evolving fields. Does not provide detailed analysis of any single approach."},{"rthcId":"RPEP-13511","title":"Targeting carA Using Optimized Antisense Peptide Nucleic Acid-Cell-Penetrating Peptide Conjugates in Acinetobacter baumannii: A Novel Antibacterial Approach.","authors":"Seo, Ju-Hui; Kim, Yoo-Jeong; Jeon, Wook-Jong; Yoo, Jung-Sik; Moon, Dong-Chan","year":2025,"journal":"International journal of molecular sciences, 26(19)","doi":"10.3390/ijms26199526","pmid":"41096791","tags":["antimicrobial-peptides","drug-discovery-screening"],"studyType":"laboratory study","evidenceStrength":"preliminary","keyFinding":"An optimized antisense peptide nucleic acid (PNA) conjugated with a cell-penetrating peptide effectively inhibited Acinetobacter baumannii growth by targeting the carA gene. A 10-mer alpha-PNA targeting the ribosomal binding site showed the strongest effect.","whyItMatters":"Acinetobacter baumannii is a dangerous multidrug-resistant hospital pathogen. This antisense approach offers a highly specific alternative to conventional antibiotics.","specificNumbers":"KFFK(FFK)2-PNA conjugate was most effective. 10-mer alpha-PNA modification targeting the ribosomal binding site of carA had the greatest inhibitory effect. Adding extra lysine residues reduced efficacy.","methodology":"Synthesized three CPP-PNA constructs targeting carA. Measured MBC, MIC, gene/protein expression (RT-qPCR, Western blot), and cytotoxicity. Optimized CPP design, PNA length, target region, and chemical modifications.","limitations":"In vitro only. Efficacy in animal infection models unknown. PNA stability and delivery in vivo not tested. Cost of PNA synthesis may limit clinical translation."},{"rthcId":"RPEP-13512","title":"Semaglutide normalizes increased cardiomyocyte calcium transients in a rat model of high fat diet-induced obesity.","authors":"Sequeira, Vasco; Theisen, Julia; Ermer, Katharina J; Oertel, Marie; Xu, Anton; Weissman, David; Ecker, Katharina; Dudek, Jan; Fassnacht, Martin; Nickel, Alexander; Kohlhaas, Michael; Maack, Christoph; Dischinger, Ulrich","year":2025,"journal":"ESC heart failure, 12(2), 1386-1397","doi":"10.1002/ehf2.15152","pmid":"39482267","tags":["glp1-receptor-agonists","cardiovascular"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Semaglutide normalized the increased calcium transients and sarcomere shortening in heart cells of obese rats. It worked by reducing sarcoplasmic reticulum calcium stores and L-type calcium channel currents without affecting the calcium pump.","whyItMatters":"This may explain why GLP-1 drugs help obese patients with or without heart failure (HFpEF) but not those with reduced ejection fraction (HFrEF). The calcium-normalizing effect targets the specific cardiac changes seen in obesity.","specificNumbers":"8 weeks high-fat diet + 8 weeks semaglutide or vehicle. HFD increased calcium transient amplitude and sarcomere shortening. Semaglutide reversed both. SR Ca2+ release and LTCC currents reduced by semaglutide. SR Ca2+ ATPase activity unchanged.","methodology":"Rats on high-fat/high-fructose diet for 8 weeks, then randomized to semaglutide or vehicle for 8 weeks. Isolated cardiomyocytes analyzed for sarcomere shortening, calcium transients, SR calcium release, LTCC currents, and SR Ca2+ ATPase activity.","limitations":"Rat model. Cardiac calcium handling may differ in humans. No functional cardiac measurements (echocardiography). Diet-induced obesity model may not replicate all human obesity phenotypes."},{"rthcId":"RPEP-13513","title":"Engineering Cell-Specific Protein Delivery Vehicles for Erythroid Lineage Cells.","authors":"Setegne, Mekedlawit T; Cabral, Aidan T; Tiwari, Anushri; Shen, Fangfang; Thiam, Hawa Racine; Dassama, Laura M K","year":2025,"journal":"ACS bio & med chem Au, 5(2), 268-282","doi":"10.1021/acsbiomedchemau.4c00098","pmid":"40255284","tags":["drug-delivery-systems","cell-biology"],"studyType":"laboratory study","evidenceStrength":"preliminary","keyFinding":"Different protein delivery vehicles (cell-penetrating peptides, bacterial toxins, injection systems) showed widely varying ability to deliver cargo into erythroid precursor cells. Targeting cell surface receptors improved some vehicles but not others.","whyItMatters":"Red blood cell precursors are notoriously hard to deliver drugs into. This systematic comparison identifies the best strategies for this challenging cell type, important for treating blood diseases like sickle cell and thalassemia.","specificNumbers":"Multiple CPPs, CPP additives, bacterial toxins, and contractile injection systems evaluated. Delivery to HUDEP-2 and CD34+ cells. Some vehicles benefited from receptor targeting; others did not.","methodology":"Evaluated cell-penetrating peptides, CPP additives, bacterial toxins, and contractile injection systems for cargo delivery to HUDEP-2 erythroid progenitor cells and primary CD34+ hematopoietic stem cells. Tested receptor-mediated targeting strategies.","limitations":"In vitro study. Cell line results may not reflect primary cell behavior in vivo. No animal testing. Delivery efficiency for therapeutic payloads not directly measured for all vehicles."},{"rthcId":"RPEP-13514","title":"Expert Consensus Statement on Simplified Glycemic Care in Patients With Type 2 Diabetes Mellitus.","authors":"Sethi, Bipin; Chowdhury, Subhankar; Jain, Sunil M; Zargar, Abdul Hamid; Chadha, Manoj; Bhattacharyya, Arpandev; Shaikh, Shehla; Makkar, Brij Mohan; Chawla, Manoj; Kalra, Pramila; Shukla, Rishi; Lodha, Sailesh; Das, Sambit; Maheshwari, Anuj; Singh, Surya K; Suryanarayana, K M; Swain, Jayashree; Gupta, Nitin R; Shrivastava, Manoj Kumar; Deka, Nilakshi; Jiwane, Dinesh; Jain, Sanjay; Swami, Onkar C","year":2025,"journal":"Cureus, 17(6), e87002","doi":"10.7759/cureus.87002","pmid":"40741551","tags":["glp1-receptor-agonists","metabolic-disorders","public-health"],"studyType":"expert consensus statement","evidenceStrength":"not applicable (consensus)","keyFinding":"Indian diabetes experts recommend simplified, combination-first approaches using SGLT-2 inhibitors and DPP-4 inhibitors with or without metformin. Fixed-dose combinations improve adherence. GLP-1RAs and SGLT-2 inhibitors are emphasized for patients with cardiovascular or kidney disease.","whyItMatters":"India faces a massive diabetes burden with unique challenges: limited healthcare access, treatment inertia, and cost constraints. Simplified care models could improve outcomes for millions.","specificNumbers":"8 advisory board meetings. Focus on SGLT-2 inhibitors, DPP-4 inhibitors, GLP-1RAs with metformin. Fixed-dose combinations recommended for adherence and cost-effectiveness.","methodology":"Expert panel of endocrinologists and diabetologists convened over 8 meetings. Reviewed current evidence and generated practice recommendations.","limitations":"Consensus statement, not a systematic review or guideline. Recommendations may reflect expert opinion where evidence is limited. India-specific considerations may not apply elsewhere."},{"rthcId":"RPEP-13515","title":"VPAC receptor positivity in comparison with mp-MRI in the diagnosis of prostate cancer: A preliminary study.","authors":"Setya, Nishant; Ghagane, Shridhar C; Nerli, Rajendra B; Bokare, Ashwin; Thakur, Madhukar L; Gomella, Leonard","year":2025,"journal":"BJUI compass, 6(4), e70006","doi":"10.1002/bco2.70006","pmid":"40264829","tags":["cancer-oncology","hormones-endocrine"],"studyType":"prospective diagnostic study","evidenceStrength":"low-moderate","keyFinding":"A urine test for VPAC receptors (which bind vasoactive intestinal peptide and PACAP) on cancer cells detected prostate cancer with 96% sensitivity and no false positives in a cohort of 61 patients with elevated PSA.","whyItMatters":"Current prostate cancer screening with PSA has many false positives. A simple urine test with 96% sensitivity and zero false positives could reduce unnecessary biopsies.","specificNumbers":"61 patients. Median age 65.3, median PSA 9.56 ng/mL. 25 (41%) had PCa on biopsy. VPAC urine test: 96% sensitivity (24/25), 4% false negative (1/25), 0% false positive. By PIRADS: 3/16 PCa in PIRADS 2, 7/21 in PIRADS 3, 7/14 in PIRADS 4, 8/8 in PIRADS 5.","methodology":"Prospective study of 61 men ≥40 years with LUTS and PSA >4 but <15 ng/mL. Voided urine VPAC receptor testing and mp-MRI performed. All underwent 12-core TRUS-guided biopsy as reference standard.","limitations":"Small sample (61 patients, 25 cancers). Single center. PSA 4-15 range only. Biopsy as reference may miss some cancers. VPAC test specifics (assay details) limited in abstract."},{"rthcId":"RPEP-13516","title":"Chemoselective sulfonyl fluoride exchange (SuFEx)-induced macrocyclization of tyrosine-containing peptides in aqueous media.","authors":"Seyrani, Hassan; Heidarzadeh Vazifehkhorani, Hossein; Outlaw, Victor K","year":2025,"journal":"Chemical science, 16(45), 21359-21367","doi":"10.1039/d5sc06993a","pmid":"41158548","tags":["peptide-manufacturing","drug-discovery-screening"],"studyType":"laboratory study (chemistry)","evidenceStrength":"preliminary","keyFinding":"A new tyrosine-selective chemistry (SuFEx) efficiently cyclizes peptides in water under mild conditions without extra reagents. Cyclic analogs of leuprorelin, beta-MSH, liraglutide, and cilengitide were made in high yield, with the RGD analog matching cilengitide's anti-adhesion potency.","whyItMatters":"Cyclic peptides are better drugs than linear ones (more stable, better cell entry) but are hard to make. This simple, selective method could accelerate peptide drug development.","specificNumbers":"Cyclizes peptides from 2 to 13 residues. STEMtide analogs of leuprorelin, beta-MSH, liraglutide, and cilengitide synthesized in high yield. RGD STEMtide: low toxicity to MCF-7 cells; potent cell adhesion inhibition comparable to cilengitide.","methodology":"Developed SuFEx-based tyrosine-selective macrocyclization in aqueous buffer. Synthesized cyclic analogs of clinically relevant peptides. Tested cytotoxicity and cell adhesion inhibition (RGD analogs vs cilengitide) in MCF-7 cells.","limitations":"In vitro proof-of-concept. In vivo stability, pharmacokinetics, and efficacy not tested. Requires tyrosine in the peptide sequence. Limited to peptides where cyclization does not disrupt activity."},{"rthcId":"RPEP-13517","title":"A Prospective Clinical Study of Ferric Citrate Hydrate for Chronic Heart Failure with Iron Deficiency Anemia.","authors":"Sezai, Akira; Sekino, Hisakuni; Taoka, Makoto; Obata, Kazuaki; Kanno, Sakie; Tanaka, Masashi","year":2025,"journal":"Life (Basel, Switzerland), 15(4)","doi":"10.3390/life15040598","pmid":"40283153","tags":["cardiovascular","nutraceuticals-supplements"],"studyType":"prospective clinical study","evidenceStrength":"moderate","keyFinding":"Oral ferric citrate hydrate improved iron stores and anemia in heart failure patients and significantly reduced natriuretic peptide levels (ANP, BNP, NT-proBNP), suggesting improvement in heart failure status. The treatment was well tolerated without GI side effects.","whyItMatters":"IV iron is the proven treatment for iron-deficient heart failure, but oral options are more convenient. This study suggests oral ferric citrate hydrate may also improve both anemia and heart failure markers.","specificNumbers":"141 patients (95 newly started, 46 switched from iron sulfate). Significant increases in hemoglobin, serum iron, TSAT, and ferritin. Significant decreases in ANP, BNP, and NT-proBNP. No notable GI side effects.","methodology":"Prospective study of 141 heart failure patients with iron deficiency anemia. Two groups: new ferric citrate hydrate starters and iron sulfate switchers. Measured iron parameters and cardiac biomarkers over treatment period.","limitations":"No placebo control or randomization. Open-label design. Cannot separate iron repletion effects from other factors. No hard clinical endpoints (hospitalization, mortality). Natriuretic peptide changes are surrogate markers."},{"rthcId":"RPEP-13518","title":"The Effect of Exenatide on Platelets Ratio Index and Fibrosis-4 Index in Obese Patients With Diabetes Mellitus.","authors":"Sezer, Gamze Ergun; Mert, Meral","year":2025,"journal":"International journal of endocrinology, 2025, 6332117","doi":"10.1155/ije/6332117","pmid":"40330499","tags":["glp1-receptor-agonists","liver-gi"],"studyType":"retrospective observational study","evidenceStrength":"low-moderate","keyFinding":"Exenatide treatment for 6 months significantly reduced the APRI liver fibrosis index in obese diabetic patients, while the FIB-4 index remained unchanged.","whyItMatters":"Fatty liver disease is common in obese diabetic patients. This study suggests exenatide may improve one marker of liver fibrosis, though results are mixed across different indices.","specificNumbers":"170 patients. Mean age 48.27 ± 11 years. APRI index decreased significantly at 3 and 6 months. FIB-4 index showed no significant change. Both indices calculated from AST, ALT, platelet counts, and age.","methodology":"Retrospective review of obese T2DM patients treated with exenatide (Jan 2015-May 2018). APRI and FIB-4 indices calculated from routine labs at baseline, 3 months, and 6 months.","limitations":"Retrospective design. No control group. Surrogate fibrosis markers, not biopsy or imaging. APRI and FIB-4 can be affected by factors other than fibrosis. Exenatide dose not specified."},{"rthcId":"RPEP-13519","title":"Nodal Expansion, Tumor Infiltration and Exhaustion of Neoepitope-Specific Th Cells After Prophylactic Peptide Vaccination and Anti-CTLA4 Therapy in Mouse Melanoma B16.","authors":"Shabalkina, Alexandra V; Izosimova, Anna V; Ryzhichenko, Ekaterina O; Shurganova, Elizaveta V; Myalik, Daria S; Maryanchik, Sofia V; Ruppel, Valeria K; Knyazev, Dmitriy I; Khilal, Nadezhda R; Barsova, Ekaterina V; Shagina, Irina A; Sharonov, George V","year":2025,"journal":"International journal of molecular sciences, 26(13)","doi":"10.3390/ijms26136453","pmid":"40650228","tags":["cancer-oncology","immunology-inflammation"],"studyType":"animal study (immunology)","evidenceStrength":"preliminary","keyFinding":"Prophylactic peptide vaccination expanded tumor-specific helper T cells in lymph nodes, but their presence in tumors did not change with vaccination. Only some tumor-specific T cell clones correlated with tumor suppression. CTLA-4 blockade did not affect tumor growth or T cell frequencies.","whyItMatters":"Understanding why peptide cancer vaccines often fail is critical. This study shows that expanding tumor-specific T cells is not enough; the right clones must infiltrate and kill tumor cells, and checkpoint blockade alone may not solve the problem.","specificNumbers":"Prophylactic p30 neoantigen vaccine in B16F0 melanoma. Tumor-specific CD4+ Th cells accumulated in tumor-draining lymph nodes but not tumors. Only some clones correlated inversely with tumor size. CTLA-4 blockade stimulated Th cell motility but did not reduce tumor growth.","methodology":"Prophylactic peptide vaccination with B16 melanoma neoantigen p30 in mice. CTLA-4 checkpoint blockade. T cells isolated from tumors, tumor-draining lymph nodes, and vaccine depots. Phenotyping, sorting, TCR repertoire sequencing. Correlation of clone frequencies with tumor size.","limitations":"Mouse melanoma model. Prophylactic (not therapeutic) vaccination. Single neoantigen tested. CTLA-4 blockade timing and dose may not be optimal. No survival data reported."},{"rthcId":"RPEP-13520","title":"Anti-virulence and anti-efflux pump activity of synthetic defensins and histatin in Candida auris.","authors":"Shaban, Siham; Patel, Mrudula; Ahmad, Aijaz","year":2025,"journal":"Microbial pathogenesis, 205, 107644","doi":"10.1016/j.micpath.2025.107644","pmid":"40306590","tags":["antimicrobial-peptides","infection-immunity"],"studyType":"laboratory study","evidenceStrength":"preliminary","keyFinding":"Three human antimicrobial peptides (hBD-3, HNP-1, histatin 5) reduced Candida auris adhesion, proteinase activity, biofilm formation, and efflux pump function. They also downregulated virulence and drug resistance genes (CDR1, CDR2, MDR1, SAP3, and others).","whyItMatters":"Candida auris is a dangerous drug-resistant fungus. These peptides attack it through multiple mechanisms including disabling its drug pumps, which could help restore sensitivity to existing antifungal drugs.","specificNumbers":"Three AMPs tested: hBD-3, HNP-1, histatin 5. Two C. auris clinical isolates. Reduced adhesion and proteinase activity at sub-MIC and MIC. Inhibited metabolic activity of growing and mature biofilms. Blocked efflux pumps (rhodamine-6-G assay). Downregulated CDR1, CDR2, MDR1, SAP3, SNQ2, PGA26, PGA7, PGA52.","methodology":"Tested human defensins and histatin against C. auris clinical isolates. Measured adhesion, proteinase activity, biofilm formation (MTT, confocal microscopy), efflux pump function (rhodamine-6-G), gene expression (RT-qPCR), and hemolytic safety.","limitations":"In vitro study with two isolates. C. auris clades differ significantly; results may not apply to all strains. In vivo efficacy and pharmacokinetics unknown."},{"rthcId":"RPEP-13521","title":"Characteristics and outcomes of cubital tunnel decompression in diabetic patients receiving glucagon-like peptide-1 receptor agonists.","authors":"Shabbir, Roban; Shamith, Simran; Parente, Paulo E L; Nicholson, Luke; Ali, Azad","year":2025,"journal":"Clinics in shoulder and elbow, 28(4), 403-410","doi":"10.5397/cise.2025.00801","pmid":"41376436","tags":["glp1-receptor-agonists","neuroscience-neurological","safety-tolerability"],"studyType":"retrospective database study","evidenceStrength":"low-moderate","keyFinding":"Perioperative GLP-1 RA use in diabetic patients undergoing cubital tunnel release was associated with fewer 90-day ER visits, fewer 2-year reoperations (5.2% vs 6.9%), and less neuropathy at 2 years (23.4% vs 30.4%).","whyItMatters":"About 35% of cubital tunnel surgery patients develop persistent neuropathy. This is the first study suggesting GLP-1RAs may have neuroprotective effects in peripheral nerve surgery.","specificNumbers":"1,766 matched pairs. Mean age 58, 46% female. 90-day ER visits: 8.9% vs 10.7% (p=0.048). 2-year reoperations: 5.2% vs 6.9% (p=0.028). 2-year neuropathy: 23.4% vs 30.4% (p<0.001). Inpatient admissions: 14.6% vs 17.2% (p=0.030). Major medical complications similar.","methodology":"TriNetX database (2015-2023). T2DM patients with primary CuTR. Active GLP-1 RA prescription at surgery vs no GLP-1RA. Propensity-score matched 1:1 on demographics, BMI, HbA1c, creatinine, and comorbidities. Outcomes captured by ICD-10-CM and CPT codes at 90 days and 2 years.","limitations":"Retrospective observational. ICD-coded neuropathy is not clinically adjudicated. Cannot separate GLP-1RA neuroprotection from better glycemic control effects. Database may not capture all confounders."},{"rthcId":"RPEP-13522","title":"Novel Trajectories Towards Possible Effects of Semaglutide for Amelioration of Reserpine-induced Fibromyalgia in Rats: Contribution of cAMP/PKA/p-CREB and M1/M2 Microglia Polarization.","authors":"Shafiek, Mena Z; Zaki, Hala F; Mohamed, Ahmed F; Ibrahim, Weam W","year":2025,"journal":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology, 20(1), 43","doi":"10.1007/s11481-025-10196-4","pmid":"40240584","tags":["glp1-receptor-agonists","pain-management","immunology-inflammation"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Semaglutide reduced fibromyalgia-like symptoms in rats by activating the cAMP/PKA/p-CREB pathway and shifting spinal cord immune cells from pro-inflammatory (M1) to anti-inflammatory (M2) states. It also reduced pain signaling molecules and improved depression and motor coordination.","whyItMatters":"Fibromyalgia is a chronic pain condition with limited treatments. If semaglutide's anti-inflammatory and pain-modulating effects translate to humans, it could offer a new treatment approach.","specificNumbers":"Reserpine 1 mg/kg/day SC for 3 days to induce FM. Semaglutide IP at 5, 10, or 20 nmol/kg daily for 14 days. Increased CD163 (M2 marker), decreased CD86 (M1 marker). Activated cAMP/PKA/CREB pathway. Reduced iNOS and TNF-alpha in DRG. Increased arginase-1 and IL-4.","methodology":"Reserpine-induced fibromyalgia model in rats. Three semaglutide dose groups vs vehicle. Assessed pain behavior, motor coordination, depression. Histopathology and immunohistochemistry of spinal cord. Measured cAMP/PKA/CREB pathway, M1/M2 markers, iNOS, TNF-alpha, arginase-1, IL-4 in dorsal root ganglia.","limitations":"Rat model. Reserpine-induced fibromyalgia model does not fully replicate human disease. Intraperitoneal route differs from clinical subcutaneous dosing. Short treatment duration."},{"rthcId":"RPEP-13523","title":"Multi-disciplinary approaches paving the way for clinically effective peptide vaccines for cancer.","authors":"Shah, Bansari A; Holden, James A; Lenzo, Jason C; Hadjigol, Sara; O'Brien-Simpson, Neil M","year":2025,"journal":"NPJ vaccines, 10(1), 68","doi":"10.1038/s41541-025-01118-9","pmid":"40204832","tags":["cancer-oncology","immunology-inflammation"],"studyType":"comprehensive review","evidenceStrength":"not applicable (review)","keyFinding":"Multi-peptide vaccines combining CD8+ killer T cell and CD4+ helper T cell epitopes with adjuvants represent the most promising approach for cancer peptide vaccines. Overcoming MHC restriction and the immunosuppressive tumor microenvironment remain key challenges.","whyItMatters":"Peptide cancer vaccines have historically underperformed. This review identifies the specific advances in immunology, vaccine chemistry, and tumor biology that may finally make them clinically effective.","specificNumbers":"Not specified (review covering vaccine design principles, MHC restriction, and tumor microenvironment strategies)","methodology":"Comprehensive review integrating vaccine chemistry, cancer immunology (CTL/CD4+ responses, MHC restriction, tumor microenvironment), and clinical trial outcomes for peptide-based cancer vaccines.","limitations":"Review of a field with a history of clinical failures. Many proposed strategies are still preclinical. Translating immunological insights to clinical success remains unproven."},{"rthcId":"RPEP-13524","title":"Chronic semaglutide treatment reveals stage-dependent changes to feeding behavior and metabolic adaptations in male mice.","authors":"Shah, Harsh; Ayala, Julio E","year":2025,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2025.07.24.666640","pmid":"40766625","tags":["glp1-receptor-agonists","weight-management"],"studyType":"animal study (metabolic phenotyping)","evidenceStrength":"preliminary","keyFinding":"Chronic semaglutide treatment in obese mice produced three distinct weight loss stages. Food intake gradually returned to normal through increased meal frequency (not meal size). Fat burning was high initially but shifted to carbohydrate burning over time. Weight rapidly returned after stopping treatment.","whyItMatters":"Weight loss responses to GLP-1 drugs vary widely. This detailed behavioral and metabolic characterization across treatment stages may help explain why some patients lose more weight than others.","specificNumbers":"Three weight loss stages identified at both room temperature and thermoneutral conditions. Stage 1: rapid weight loss with reduced food intake and increased lipid oxidation. Stage 2: gradual weight loss with normalizing food intake. Stage 3: weight maintenance. Post-treatment: rapid weight regain with increased meal size and frequency.","methodology":"Chronic semaglutide treatment and post-treatment recovery in diet-induced obese male mice at room temperature and thermoneutral conditions. Measured food intake, meal patterns (size, frequency), energy expenditure, locomotor activity, and substrate oxidation (lipid vs carbohydrate) throughout.","limitations":"Preprint (not peer reviewed). Male mice only. Mouse metabolism differs from human. Room temperature for mice induces cold stress. No drug dose optimization explored."},{"rthcId":"RPEP-13525","title":"Different dietary compositions alter pubertal onset in Wistar rats.","authors":"Shah, Harsh; Dan, Nehareeka; Salunke, Ankita; Ramachandran, A V; Pandya, Parth","year":2025,"journal":"Nutritional neuroscience, 28(12), 1445-1462","doi":"10.1080/1028415X.2025.2522454","pmid":"40576783","tags":["neuroscience-neurological","hormones-endocrine"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"High-fat, high-carbohydrate, and cafeteria diets accelerated puberty onset in female rats. This was associated with upregulation of kisspeptin, POMC, leptin, and GnRH signaling and downregulation of NPY, AgRP, and MKRN3 in the hypothalamus, with increased histone acetylation.","whyItMatters":"Early puberty is linked to health risks including obesity and reproductive problems. This study shows how diet directly alters the brain's puberty-triggering signals through neuropeptide and epigenetic changes.","specificNumbers":"5 diet groups for 21 days post-weaning. HFD, HCD, and CafD groups showed early vaginal opening, increased FSH, LH, estradiol. Upregulated: Kiss1, Kiss1r, Pomc, Lep, Lepr, Gnrh. Downregulated: Npy, Agrp, Mkrn3. Higher histone acetylation in hypothalamus of HFD and HCD groups.","methodology":"Female Wistar rats weaned into 5 diet groups for 21 days. Monitored body weight and vaginal opening. Post-sacrifice: hormonal analysis, hypothalamic gene expression (RT-qPCR), protein expression, immunolocalization, and global histone acetylation analysis.","limitations":"Rat model. 21-day dietary intervention. Human puberty involves additional social and genetic factors. Epigenetic changes are associative, not proven causal. Small sample sizes typical of animal studies."},{"rthcId":"RPEP-13526","title":"Tirzepatide-Induced Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) Presenting With Seizures.","authors":"Shah, Islam; Sennik, Devesh; Veettil, Fahas Ali Vattiyam","year":2025,"journal":"JCEM case reports, 3(12), luaf261","doi":"10.1210/jcemcr/luaf261","pmid":"41179268","tags":["glp1-receptor-agonists","safety-tolerability","hormones-endocrine"],"studyType":"case report","evidenceStrength":"low","keyFinding":"A 63-year-old woman developed severe hyponatremia (sodium 122 mmol/L) and seizures from SIADH just 4 days after starting tirzepatide for weight loss. She had no prior medical history. Stopping tirzepatide and fluid restriction resolved the condition.","whyItMatters":"SIADH causing seizures is a potentially life-threatening complication not widely recognized with GLP-1 drugs. This case warns clinicians to monitor electrolytes when starting tirzepatide, even in low-risk patients.","specificNumbers":"63-year-old woman. No past medical history. Tonic-clonic seizures 4 days after starting tirzepatide. Serum sodium 122 mmol/L. Low serum osmolality. High urine osmolality and urine sodium consistent with SIADH. Full recovery after discontinuation and fluid restriction.","methodology":"Single case report with clinical documentation, laboratory workup confirming SIADH, exclusion of other causes, and follow-up after drug discontinuation.","limitations":"Single case. Cannot determine incidence of this complication. No rechallenge performed. Other unrecognized causes cannot be completely excluded."},{"rthcId":"RPEP-13527","title":"Weight Loss That Lasts: Reviewing the Long-Term Impact of GLP-1 Receptor Agonists.","authors":"Shah, Md Yasir; Mohammad, Ahmad; Bashir Ahmed Samejo, Rabia; Rana, Siddharth; Singla, Shivam; Aurangzeb, Raja Irsalan; Tariq, Muhammad M; Zamir, Muhammad Hamza; Farooq, Umer; Aurangzeb, Raja Faizan; Singla, Bhavna; Rehman, Abdur","year":2025,"journal":"Cureus, 17(7), e88334","doi":"10.7759/cureus.88334","pmid":"40837892","tags":["glp1-receptor-agonists","weight-management","clinical-trials"],"studyType":"systematic review","evidenceStrength":"moderate","keyFinding":"GLP-1 receptor agonists (semaglutide, liraglutide, tirzepatide, exenatide) show sustained weight loss and acceptable safety profiles across trials lasting 40-120 weeks. GI side effects are the most common adverse events. Obesity should be treated as a chronic condition requiring long-term medication.","whyItMatters":"Compiles the long-term evidence supporting GLP-1RAs for obesity, reinforcing that these drugs maintain efficacy over years and that obesity management is a long-term commitment.","specificNumbers":"Studies from 2018-2025. Treatment durations 40-120 weeks. Agents: semaglutide, liraglutide, tirzepatide, exenatide. Populations: adults with/without T2D, adolescents with severe obesity. Sustained weight loss. GI side effects most common.","methodology":"Systematic review of high-quality RCTs evaluating long-term efficacy and safety of GLP-1RAs for obesity (2018-2025). Assessed weight loss, glycemic control, and adverse events.","limitations":"Limited follow-up beyond 2 years. Population diversity in available trials is limited. Real-world generalizability uncertain. Weight regain after cessation not fully characterized across all agents."},{"rthcId":"RPEP-13528","title":"Macitentan for Heart Failure With Preserved or Mildly Reduced Ejection Fraction and Pulmonary Vascular Disease: Results of the SERENADE Randomized Clinical Trial and Open-Label Extension Study.","authors":"Shah, Sanjiv J; Bonderman, Diana; Borlaug, Barry A; Cleland, John G F; Lack, Gabriela; Lu, Wentao; Voors, Adriaan A; Zannad, Faiez; Gladwin, Mark T","year":2025,"journal":"Circulation. Heart failure, 18(3), e011381","doi":"10.1161/CIRCHEARTFAILURE.123.011381","pmid":"40066571","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13529","title":"Comparative Effectiveness of Sodium-Glucose Cotransporter 2 (SGLT-2) Inhibitors and Glucagon-like Peptide-1 (GLP-1) Receptor Agonists in Reducing Adverse Cardiovascular Events in Type 2 Diabetes.","authors":"Shah, Syed Zakir; Khan, Rahema; Moeez, Sadaf; Kumar, Sanjay; Ejaz, Muhammad Umar; Aslam, Usman; Mustafa, Mian Waqar; Ashraf, Mahwish; Mustafa, Imtiaz; Asim, Fahad","year":2025,"journal":"Cureus, 17(9), e92048","doi":"10.7759/cureus.92048","pmid":"41080335","tags":["glp1-receptor-agonists","cardiovascular","metabolic-disorders"],"studyType":"retrospective comparative study","evidenceStrength":"low","keyFinding":"In 200 Pakistani T2DM patients, SGLT-2 inhibitors showed lower MACE rates (18% vs 30%), higher event-free survival, and a 42% reduced MACE risk compared to GLP-1 RAs over 18.6 months. SGLT-2i also showed greater blood pressure and BMI reductions.","whyItMatters":"Head-to-head comparisons of SGLT-2 inhibitors and GLP-1RAs are rare, especially in South Asian populations. These results favor SGLT-2i for cardiovascular risk reduction in this specific population.","specificNumbers":"200 patients (100 per group). MACE: 18% SGLT-2i vs 30% GLP-1RA (p=0.04). HR 0.58 (95% CI 0.35-0.95, p=0.03). Mean follow-up 18.6 ± 3.1 months. Greater SBP reduction with SGLT-2i (p=0.02). Greater BMI reduction with SGLT-2i (p=0.01). HbA1c difference not significant (p=0.42).","methodology":"Retrospective study at Combined Military Hospital, Lahore, Pakistan. 200 T2DM patients (100 SGLT-2i, 100 GLP-1RA). Comparable baseline characteristics. Primary outcome: MACE. Secondary: HbA1c, blood pressure, lipids, BMI. Kaplan-Meier survival and Cox regression analysis.","limitations":"Small single-center study. Retrospective. Non-randomized. Specific drug agents within classes not detailed. 18-month follow-up is relatively short. Pakistani population may not generalize."},{"rthcId":"RPEP-13530","title":"Determinants of Liraglutide Treatment Discontinuation in Type 1 Diabetes: A Post Hoc Analysis of ADJUNCT ONE and ADJUNCT TWO Randomized Placebo-Controlled Clinical Studies.","authors":"Shah, Viral N; Agesen, Rikke M; Bardtrum, Lars; Christiansen, Erik; Snaith, Jennifer; Greenfield, Jerry R","year":2025,"journal":"Journal of diabetes science and technology, 19(2), 321-331","doi":"10.1177/19322968241305647","pmid":"39717993","tags":["glp1-receptor-agonists","metabolic-disorders"],"studyType":"post-hoc analysis of randomized controlled trials","evidenceStrength":"moderate","keyFinding":"T1D patients with longer disease duration and undetectable C-peptide were more likely to discontinue liraglutide due to adverse events. Lower BMI predicted dropout regardless of treatment group. These factors may help identify T1D patients most likely to tolerate adjunctive liraglutide.","whyItMatters":"GLP-1RAs are being explored for T1D, but discontinuation is common. Identifying who tolerates them could improve clinical outcomes and guide patient selection.","specificNumbers":"Non-completers had lower BMI (27.8 vs 29.8 kg/m2, p<0.001), shorter T1D duration, lower insulin doses, and higher proportion with undetectable C-peptide (91.5% vs 81.3%). T1D duration and C-peptide differed between completers/non-completers only in liraglutide (not placebo) groups.","methodology":"Post-hoc analysis of ADJUNCT ONE (NCT01836523) and ADJUNCT TWO (NCT02098395). Compared baseline characteristics and AE rates between completers and non-completers. Liraglutide 0.6, 1.2, or 1.8 mg vs placebo as adjunct to insulin in T1D.","limitations":"Post-hoc analysis. Cannot prove causation for dropout predictors. C-peptide measurement methods varied. Non-completers defined by AEs/tolerance, not all-cause dropout."},{"rthcId":"RPEP-13531","title":"Semaglutide in Adults with Type 1 Diabetes and Obesity.","authors":"Shah, Viral N; Akturk, Halis K; Kruger, Davida; Ahmann, Andrew; Bhargava, Anuj; Bakoyannis, Giorgos; Pyle, Laura; Snell-Bergeon, Janet K","year":2025,"journal":"NEJM evidence, 4(8), EVIDoa2500173","doi":"10.1056/EVIDoa2500173","pmid":"40550013","tags":["glp1-receptor-agonists","metabolic-disorders","clinical-trials"],"studyType":"randomized controlled trial","evidenceStrength":"high","keyFinding":"In adults with type 1 diabetes and obesity using automated insulin delivery, semaglutide 1 mg weekly achieved the composite endpoint (>70% time in range, <4% time below range, and ≥5% weight loss) in 36% vs 0% on placebo. HbA1c improved 0.3 points and weight decreased 8.8 kg more than placebo.","whyItMatters":"This is the first rigorous RCT showing semaglutide significantly improves both glucose control and weight in type 1 diabetes. It could change treatment paradigms for the growing number of T1D patients with obesity.","specificNumbers":"72 adults randomized 1:1. BMI ≥30. 26 weeks. Composite endpoint met: 36% semaglutide vs 0% placebo (difference 36 pp, 95% CI 20.6-52.2, p<0.001). HbA1c difference: -0.3 pp. Time in range difference: +8.8 pp. Weight difference: -8.8 kg (95% CI -10.6 to -7.0). 2 severe hypoglycemia events per group. Zero DKA events.","methodology":"26-week double-blind RCT (ADJUST-T1D). 72 adults with T1D, BMI ≥30, using automated insulin delivery. Semaglutide up to 1 mg weekly vs placebo. Primary composite: CGM time in range >70% + time below range <4% + ≥5% weight loss. NCT05537233.","limitations":"Small trial (72 patients). 26-week duration. Only BMI ≥30 included. All used AID systems, limiting generalizability. Semaglutide not yet approved for T1D. Longer-term safety data needed."},{"rthcId":"RPEP-13532","title":"Treatment satisfaction and time in range after 16 weeks of treatment with iGlarLixi in insulin-naive adults with suboptimally controlled type 2 diabetes.","authors":"Shah, Viral N; Dex, Terry; Meneghini, Luigi; Rodrigues, Amélie; Polonsky, William H","year":2025,"journal":"Diabetes, obesity & metabolism, 27(5), 2523-2530","doi":"10.1111/dom.16251","pmid":"39950217","tags":["glp1-receptor-agonists","metabolic-disorders","clinical-trials"],"studyType":"phase 4 clinical trial (single-arm, exploratory analysis)","evidenceStrength":"low-moderate","keyFinding":"iGlarLixi (insulin glargine + lixisenatide combination) doubled time in range from 26.4% to 52.7% at 16 weeks in insulin-naive T2D patients poorly controlled on oral medications, with a trend toward improved treatment satisfaction.","whyItMatters":"Many T2D patients delay insulin initiation. iGlarLixi offers a one-injection combination that significantly improves glucose control and may improve patient acceptance of injectable therapy.","specificNumbers":"124 participants. Time in range: 26.4% to 52.7% at 16 weeks. DM-SAT overall score: 0.59 to 0.78. Weak positive correlation between TIR improvement and satisfaction (r=0.14). 95.9% completed baseline DM-SAT, 87.0% at Week 16.","methodology":"Single-arm, open-label, Phase 4 study. 16 weeks of iGlarLixi in insulin-naive T2D patients on ≥2 OADs ± GLP-1RA with HbA1c 9-13%. Blinded CGM at baseline and weeks 14-16. DM-SAT questionnaire at baseline and end-of-treatment.","limitations":"Single-arm, no comparator. Open-label. Exploratory satisfaction analysis. Weak correlation between TIR and satisfaction. Short duration. Selection bias possible."},{"rthcId":"RPEP-13533","title":"Effect of spironolactone on monocyte subsets in atrial fibrillation: IMPRESS-AF randomised controlled trial.","authors":"Shahid, Farhan; Shantsila, Eduard; Shantsila, Alena; Lip, Gregory Y H","year":2025,"journal":"Scientific reports, 15(1), 27410","doi":"10.1038/s41598-024-74592-1","pmid":"40721437","tags":["cardiovascular","immunology-inflammation"],"studyType":"randomized controlled trial (substudy)","evidenceStrength":"moderate","keyFinding":"Spironolactone temporarily reduced pro-inflammatory monocyte markers at 12 months in atrial fibrillation patients, but the effect disappeared by 24 months. A specific monocyte subset (Mon1) independently predicted better diastolic function at 2 years.","whyItMatters":"This reveals a novel anti-inflammatory mechanism of spironolactone in atrial fibrillation and identifies a monocyte subset that may influence heart function, opening new therapeutic targets.","specificNumbers":"225 patients (90% of IMPRESS-AF). Age 72, 78% male. At 12 months: fewer Mon3 (50 vs 60 cells/mcL, p=0.02), lower CD14 on Mon1 (p=0.04). No difference at 24 months. High Mon1 at 12 months predicted lower E/e' at 24 months (p=0.02).","methodology":"Substudy of IMPRESS-AF RCT (spironolactone 25 mg vs placebo for 2 years in AF). Monocyte subsets analyzed by flow cytometry at 12 and 24 months. Peak VO2, diastolic function (E/e'), and BNP measured. Linear regression for outcomes.","limitations":"Exploratory substudy. Transient monocyte effects may not be clinically meaningful. Multiple comparisons not fully corrected. Monocyte-outcome associations are observational within a trial."},{"rthcId":"RPEP-13534","title":"Bioactivity of Marine-Derived Peptides and Proteins: A Review.","authors":"Shahidi, Fereidoon; Saeid, Abu","year":2025,"journal":"Marine drugs, 23(4)","doi":"10.3390/md23040157","pmid":"40278278","tags":["nutraceuticals-supplements","antimicrobial-peptides","drug-discovery-screening"],"studyType":"comprehensive review","evidenceStrength":"not applicable (review)","keyFinding":"Marine-derived peptides (3-40 amino acids) from fish, algae, mollusks, and crustaceans show antioxidant, antihypertensive, antidiabetic, antimicrobial, anti-inflammatory, and anticancer activities. Production scale-up, stability, and bioavailability remain major challenges.","whyItMatters":"The ocean is a largely untapped source of bioactive peptides. This review maps the landscape of marine peptide bioactivities and identifies the gaps between discovery and commercial application.","specificNumbers":"Peptides typically 3-40 amino acids (most commonly 2-20). Sources: fish, algae, mollusks, crustaceans, microbes, marine by-products. Activities: antioxidant, antihypertensive, antidiabetic, antimicrobial, anti-inflammatory, anticoagulant, anticancer, immunoregulatory, wound-healing.","methodology":"Comprehensive review of marine-derived peptide and protein bioactivities, extraction methods (enzymatic hydrolysis, ultrafiltration, HPLC, molecular docking), and industrial application challenges.","limitations":"Review article. Most bioactivities demonstrated in vitro. Few marine peptides have reached clinical trials. Bioavailability and stability issues are largely unresolved."},{"rthcId":"RPEP-13535","title":"Fasting Duration, Not Timing of Last GLP-1 Dose, Predicts Aspiration Risk Indicators: A Prospective Point-of-Care Gastric Ultrasound Study.","authors":"Shahidifar, Enayat; Lesniowska, Marlena; Deschenes, Ester; Polcha, Gregory; Manzo, Carl; Barreiro, Timothy; Bigdeli, Ghazaleh; Hemmat, Arman; Brine, Patrick; Malik, Alexander; Song, Gengqing","year":2025,"journal":"Digestive diseases and sciences","doi":"10.1007/s10620-025-09570-2","pmid":"41266825","tags":["glp1-receptor-agonists","safety-tolerability"],"studyType":"prospective observational study","evidenceStrength":"moderate","keyFinding":"Fasting duration, not time since last GLP-1RA dose, better predicted reduced stomach contents before procedures. GLP-1 users had similar rates of solid stomach contents as non-users (5.4% vs 5.0%) when fasting 13+ hours. Ultrasound-guided assessment was more useful than blanket medication withholding.","whyItMatters":"Current guidelines inconsistently recommend withholding GLP-1 drugs before surgery. This study suggests fasting time matters more than when the last dose was taken, supporting individualized pre-procedure assessment over blanket drug withholding.","specificNumbers":"134 adults (74 GLP-1RA users, 60 controls). Mean fasting 13.0 ± 2.4 h. Solid content: 5.4% GLP-1 vs 5.0% control (p=0.563). GLP-1 users with solids fasted less (10.88 vs 13.14 h, p=0.022). Fasting associated with lower gastric volume (β=-2.26 mL/h). Time since last dose not significant.","methodology":"Prospective observational study. 134 adults from internal medicine clinic fasting 8-16 h. Point-of-care gastric ultrasound. Compared GLP-1RA users vs controls. Subgroup analysis and multivariable regression for fasting duration, dose timing, and gastric content.","limitations":"Moderate sample. Non-surgical setting (clinic patients, not pre-operative). Observational design. Some GLP-1RA users had solids despite adequate fasting. Cannot exclude aspiration risk entirely."},{"rthcId":"RPEP-13536","title":"Formulation of pH-responsive nanoplexes based on an antimicrobial peptide and sodium alginate for targeted delivery of vancomycin against resistant bacteria.","authors":"Shahin, Shourok; Omolo, Calvin A; Elhassan, Eman; Ismail, Eman A; Farukh, Sania; Govender, Jasoda; Faya, Mbuso; Govender, Thirumala","year":2025,"journal":"Biological chemistry, 406(8-9), 369-389","doi":"10.1515/hsz-2025-0142","pmid":"41189473","tags":["antimicrobial-peptides","drug-delivery-systems"],"studyType":"laboratory and animal study","evidenceStrength":"preliminary","keyFinding":"pH-responsive nanoplexes combining a plant antimicrobial peptide with vancomycin showed 2-fold stronger activity against MRSA, 5-fold better biofilm eradication, and 4-5 fold reduced bacterial burden in kidneys, liver, and blood of mice with MRSA infection.","whyItMatters":"MRSA is a leading cause of hospital deaths. This nanoparticle delivery system makes vancomycin far more effective by combining it with an antimicrobial peptide in a pH-triggered release system.","specificNumbers":"Particle size 159.5 nm. Encapsulation efficiency 82.34%. 2-fold enhanced activity vs S. aureus and MRSA. 5-fold greater MRSA biofilm eradication. In vivo: 5-fold reduction in kidney MRSA, 4-fold in liver and blood. pH-accelerated VCM release at acidic pH.","methodology":"Formulated nanoplexes from plant AMP and sodium alginate loaded with vancomycin. Characterized size, zeta potential, encapsulation, pH-responsive release. In vitro: MIC, biofilm eradication. In vivo: MRSA systemic infection in mice, organ bacterial burden, inflammation markers.","limitations":"Specific plant AMP not named in abstract. Mouse model may not reflect human MRSA infection. Toxicity profile needs more characterization. Manufacturing scalability not addressed."},{"rthcId":"RPEP-13537","title":"Production of a Dulaglutide Analogue by Apoptosis-Resistant Chinese Hamster Ovary Cells in a 3-Week Fed-Batch Process.","authors":"Shaifutdinov, Rolan R; Sinegubova, Maria V; Vorobiev, Ivan I; Prokhorova, Polina E; Podkorytov, Alexey B; Orlova, Nadezhda A","year":2025,"journal":"Pharmaceuticals (Basel, Switzerland), 18(12)","doi":"10.3390/ph18121896","pmid":"41471386","tags":["glp1-receptor-agonists","peptide-manufacturing"],"studyType":"laboratory study (bioprocess development)","evidenceStrength":"preliminary","keyFinding":"A new CHO cell manufacturing platform achieved 1.05 g/L production of a dulaglutide analog with ≥95% monomer purity and better receptor activation (EC50 52 pM) than the original drug (76 pM). The cell line remained stable for 69 days without selection pressure.","whyItMatters":"Dulaglutide supply shortages affect some regions. This high-yield biosimilar manufacturing platform could increase global access to this important diabetes drug.","specificNumbers":"1.05 g/L titer in fed-batch culture. Cell-specific productivity up to 22 pg/cell/day. ≥95% monomer by SEC-HPLC. EC50: 52 pM (produced) vs 76 pM (reference). Stable for 69 days without MTX/MSX. ~30% titer increase from second plasmid transfection.","methodology":"Sequential transfection of dulaglutide expression plasmids into apoptosis-resistant CHO 4BGD cells. Two-step transgene amplification (MTX then MSX). Cell cloning pipeline. Fed-batch culture optimization. Product characterization by SEC-HPLC and GLP-1R/CRE-Luc bioassay.","limitations":"Lab-scale production. Industrial-scale validation needed. Glycosylation profile comparison to original not detailed. Regulatory pathway for biosimilar approval not addressed."},{"rthcId":"RPEP-13538","title":"A Case of Pulmonary Hemorrhage, Supratherapeutic International Normalized Ratio (INR), and Anti-neutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis: Unmasking a Potential Link to Tirzepatide.","authors":"Shakour, Husam; Mumtaz, Reem; Feghali, Edwin; Abu-Samra, Abdel-Ghanie","year":2025,"journal":"Cureus, 17(3), e80539","doi":"10.7759/cureus.80539","pmid":"40225446","tags":["glp1-receptor-agonists","safety-tolerability","immunology-inflammation"],"studyType":"case report","evidenceStrength":"low","keyFinding":"A 64-year-old man on warfarin developed supratherapeutic INR (8.7), pulmonary hemorrhage, acute kidney injury, and ANCA-associated vasculitis shortly after increasing his tirzepatide dose. He required corticosteroids, plasmapheresis, rituximab, and dialysis but died.","whyItMatters":"This case raises two safety concerns: tirzepatide may interact with warfarin metabolism (causing dangerous bleeding) and may potentially trigger autoimmune vasculitis. Both need further investigation.","specificNumbers":"64-year-old male. INR 8.7 (target typically 2-3). Elevated c-ANCA levels. Diffuse alveolar hemorrhage. Acute kidney injury. Treatments: corticosteroids, plasmapheresis, rituximab, hemodialysis. Patient expired.","methodology":"Single case report with clinical documentation. Renal biopsy was pending at time of death.","limitations":"Single case. Causality not established. Multiple potential confounders. Renal biopsy not completed. ANCA vasculitis may have been pre-existing and unmasked rather than caused by tirzepatide."},{"rthcId":"RPEP-13539","title":"Therapeutic potential of targeting ceramide for early cardiometabolic lipotoxicity in vivo study.","authors":"Shalaby, Youssef M; Al-Zohily, Bashar; Sudhadev, Manjusha; Nemmar, Abderrahim; Al-Salam, Suhail; Akawi, Nadia","year":2025,"journal":"Scientific reports, 16(1), 1599","doi":"10.1038/s41598-025-31001-5","pmid":"41392183","tags":["metabolic-disorders","cardiovascular"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"In rats on high-fat diet, ceramide levels (CerC16:0 and CerC18:0) rose in blood, heart, and liver before traditional metabolic markers changed. Sitagliptin (a DPP-4 inhibitor) outperformed liraglutide and saxagliptin in reducing ceramides and restoring cardioprotective signaling.","whyItMatters":"Ceramides may serve as early biomarkers for cardiometabolic damage, detectable before glucose and cholesterol rise. Sitagliptin's ceramide-lowering effect suggests a novel cardioprotective mechanism beyond blood sugar control.","specificNumbers":"HFD elevated cardiac CerC18:0 to 1.37 ± 0.103 nmol/g (p<0.001). Ceramide changes preceded glucose/cholesterol/triglyceride alterations. Pilot: n=24; extended: n=48. Sitagliptin reduced CerC16:0/24:0 and CerC18:0/24:0 ratios. Enhanced urinary CerC16:0 excretion (p<0.01). Restored eNOS, pAKT, cTnT signaling.","methodology":"HFD-fed rats. Pilot (n=24): compared sitagliptin, liraglutide, saxagliptin. Extended (n=48): focused on sitagliptin. Measured ceramide levels in serum, heart, liver. Assessed oxidative stress, apoptosis, steatosis, and cardioprotective signaling (eNOS, pAKT, cTnT).","limitations":"Rat model. Sitagliptin's superiority may not translate to humans. Small sample sizes. No clinical outcomes measured. Mechanism of ceramide reduction not fully elucidated."},{"rthcId":"RPEP-13540","title":"2'-Fucosyllactose synbiotics with Bifidobacterium bifidum to improve intestinal transcriptional function and gut microbiota in constipated mice.","authors":"Shan, Yi; Zheng, Miaomiao; Liang, Weiwei; Ouyang, Le; Wang, Shumei","year":2025,"journal":"Food research international (Ottawa, Ont.), 217, 116840","doi":"10.1016/j.foodres.2025.116840","pmid":"40597542","tags":["liver-gi","nutraceuticals-supplements"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"A synbiotic combination of 2'-fucosyllactose and Bifidobacterium bifidum improved constipation in mice by regulating gut peptides (increasing gastrin and substance P, suppressing VIP), reducing inflammation, strengthening the gut barrier, and promoting beneficial bacteria like Akkermansia.","whyItMatters":"Constipation affects millions and is often poorly treated. This synbiotic approach targets multiple mechanisms simultaneously, suggesting a more comprehensive treatment strategy than probiotics or prebiotics alone.","specificNumbers":"Increased gastrin and substance P secretion. Suppressed vasoactive intestinal peptide. Reduced TNF-alpha, IL-1beta, IL-6. Increased IL-10. Upregulated tight junction proteins (ZO-1, Claudin-1, Occludin). Promoted Akkermansia, Bifidobacterium, Parabacteroides.","methodology":"Constipation induced in mice. Treated with 2'-FL + B. bifidum combination. Assessed defecation, GI regulatory peptides, inflammatory cytokines, gut barrier proteins, transcriptomics, and 16S rRNA microbiome analysis.","limitations":"Mouse model. Constipation model may not replicate all human forms. Transcriptomic changes are associative. Dose optimization not described. No human clinical data."},{"rthcId":"RPEP-13541","title":"An in vitro model demonstrating homeostatic interactions between reconstructed human gingiva and a saliva-derived multispecies biofilm.","authors":"Shang, Lin; Roffel, Sanne; Slomka, Vera; D'Agostino, Eleanor M; Metris, Aline; Buijs, Mark J; Brandt, Bernd W; Deng, Dongmei; Gibbs, Susan; Krom, Bastiaan P","year":2025,"journal":"Microbiome, 13(1), 58","doi":"10.1186/s40168-025-02033-w","pmid":"40022258","tags":["antimicrobial-peptides","oral-dental-health","immunology-inflammation"],"studyType":"laboratory study (in vitro model)","evidenceStrength":"preliminary","keyFinding":"A lab-grown human gum tissue model maintained its integrity while supporting a stable, diverse oral bacterial community for 4 days. The tissue responded by upregulating antimicrobial peptides (elafin, human beta-defensin-2) and inflammatory cytokines, demonstrating active host-microbe communication.","whyItMatters":"Most oral research focuses on disease. This model allows scientists to study how healthy gums maintain balance with bacteria, which is key to preventing gum disease rather than just treating it.","specificNumbers":"Biofilm grew from inoculation to day 2, then stabilized through day 4. Dominated by Streptococcus, Haemophilus, Neisseria. No significant changes in tissue metabolic activity, histology, or proliferation. Upregulated: elafin, hBD-2. Increased secretion: IL-6, CXCL1, CXCL8, CCL5, CCL20.","methodology":"Reconstructed human gingiva (keratinocytes + fibroblasts) inoculated with pooled human saliva in different media. Co-cultured 2-4 days. Biofilm: viable counting + 16S sequencing. Tissue: MTT, histology, Ki67, AMP expression, cytokine secretion.","limitations":"In vitro model. Lacks saliva flow, immune cells, and systemic factors. 4-day duration is short. Pooled saliva may not represent individual variation. No disease model comparison."},{"rthcId":"RPEP-13542","title":"Neuro-immune axis in atherosclerosis: mechanisms of regulation and therapeutic opportunities.","authors":"Shang, Yuxin; Pan, Yuqing; Xie, Lingling; Zhao, Yan; Mao, Wei; Chen, Tingting","year":2025,"journal":"Frontiers in immunology, 16, 1619338","doi":"10.3389/fimmu.2025.1619338","pmid":"40977707","tags":["cardiovascular","neuroscience-neurological","immunology-inflammation"],"studyType":"narrative review","evidenceStrength":"not applicable (review)","keyFinding":"Neuropeptides including PACAP, CGRP, NPY, and galanin regulate immune cell behavior in atherosclerotic blood vessels. Neuroimmune cardiovascular interfaces (NICIs) serve as key sites where nervous and immune systems interact to drive or resolve arterial inflammation.","whyItMatters":"Atherosclerosis is the leading cause of death worldwide. Understanding the nerve-immune connection adds a new therapeutic layer beyond cholesterol-lowering drugs, with interventions like vagus nerve stimulation already showing promise in animal models.","specificNumbers":"Neuropeptides reviewed: PACAP, CGRP, NPY, galanin. Interventions discussed: vagus nerve stimulation, alpha7 nAChR agonists. Primarily experimental model data.","methodology":"Narrative review of neuroimmune mechanisms in atherosclerosis, focusing on neuropeptide roles, NICIs, autonomic neural circuits, and translational neuromodulatory interventions.","limitations":"Mostly preclinical evidence. NICIs are newly defined and not yet validated as therapeutic targets in humans. Complex bidirectional interactions are hard to translate clinically."},{"rthcId":"RPEP-13543","title":"Alaria esculenta, Ulva lactuca, and Palmaria palmata as Potential Functional Food Ingredients for the Management of Metabolic Syndrome.","authors":"Shannon, Emer; Hayes, Maria","year":2025,"journal":"Foods (Basel, Switzerland), 14(2)","doi":"10.3390/foods14020284","pmid":"39856950","tags":["nutraceuticals-supplements","cardiovascular"],"studyType":"laboratory study (in vitro)","evidenceStrength":"preliminary","keyFinding":"Seaweed extracts matched or exceeded the enzyme-inhibiting activity of prescription drugs: Palmaria palmata peptides matched captopril for ACE-1 inhibition, and Alaria esculenta polyphenols outperformed both acarbose and orlistat for alpha-amylase and lipase inhibition.","whyItMatters":"Metabolic syndrome (high blood pressure, diabetes, obesity) affects millions. Natural seaweed-derived alternatives could provide dietary approaches to managing these conditions with fewer side effects.","specificNumbers":"P. palmata peptides ACE-1 IC50: 94.29 mcg/mL (vs captopril 91.83). A. esculenta polyphenols alpha-amylase IC50: 147.04 (vs acarbose 185.67). A. esculenta lipase IC50: 106.21 (vs orlistat 139.74). U. lactuca polysaccharides alpha-amylase IC50: 168.06 (vs acarbose 185.67).","methodology":"In vitro enzyme inhibitory assays for ACE-1, alpha-amylase, and lipase. Compared seaweed extracts (peptides, polyphenols, polysaccharides) to reference drugs. Proximate analysis of protein, fiber, and fatty acid content.","limitations":"In vitro assay only. Enzyme inhibition in a test tube does not guarantee in vivo efficacy. Bioavailability after oral consumption unknown. Seaweed composition varies by season and location."},{"rthcId":"RPEP-13544","title":"Great Expectations: Semaglutide as Antidiabetic Weight Management in a Psychiatric Hospital.","authors":"Shannon, Krysta; Shyh, Grace","year":2025,"journal":"Journal of pharmacy practice, 38(3), 351-356","doi":"10.1177/08971900241294122","pmid":"39438027","tags":["glp1-receptor-agonists","mental-health","metabolic-disorders"],"studyType":"case series (2 cases)","evidenceStrength":"low","keyFinding":"In 2 psychiatric inpatients with T2D on psychotropic medications causing weight gain, weekly semaglutide improved blood glucose levels and prevented weight gain despite ongoing psychotropic therapy.","whyItMatters":"Psychiatric medications commonly cause weight gain and metabolic problems. GLP-1 drugs could help manage these side effects, but use in inpatient psychiatric settings is rarely reported.","specificNumbers":"2 patients. Both on chronic psychotropic medications. Weekly semaglutide improved glucose levels and prevented weight gain. Specific doses and outcomes not detailed in abstract.","methodology":"Two case descriptions from inpatient psychiatric care showing semaglutide effects on glucose and weight during psychotropic medication use.","limitations":"Only 2 cases. No control comparison. Short observation period implied. Cannot generalize to all psychiatric patients. Cost and formulary issues not resolved."},{"rthcId":"RPEP-13545","title":"The GLP-1 Receptor Agonist Dulaglutide Attenuates Hepatic Steatosis in Obesity via a Weight-Independent Mechanism.","authors":"Shantaram, Dharti; Rima, Xilal Y; Bradley, David; Liu, Joey Z; Wright, Valerie P; Amari, Anastasiia; Jalilvand, Anahita; Rottinghaus, Joseph; Fernandes, Jaden M; Smith, Alan J; Middendorf, Dana; Yearsley, Martha; Roy, Debasish; Hsueh, Willa A","year":2025,"journal":"Diabetes, 74(9), 1512-1524","doi":"10.2337/db24-0861","pmid":"40663700","tags":["glp1-receptor-agonists","liver-gi"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Dulaglutide improved fatty liver in obese animals through weight-independent mechanisms: reducing de novo fat production, destabilizing fat droplets, lowering inflammation and oxidative stress in the liver, and reducing fat breakdown in adipose tissue.","whyItMatters":"Separating weight-dependent from weight-independent drug effects is crucial for understanding how GLP-1 drugs help the liver. This shows dulaglutide has direct liver benefits beyond what weight loss alone would produce.","specificNumbers":"Reduced de novo lipogenesis, lipid droplet stability, inflammation, and oxidative stress in liver. Reduced lipolysis in adipose tissue. Weight loss important for cardiovascular risk reduction but liver effects were weight-independent.","methodology":"Obesity animal model. Dulaglutide treatment with weight-independent analyses of liver steatosis, de novo lipogenesis, lipid droplet markers, inflammation, oxidative stress, and adipose tissue lipolysis.","limitations":"Animal study. Weight-independent design has inherent complexity. Specific animal species and study design details limited in abstract. Human confirmation needed."},{"rthcId":"RPEP-13546","title":"Glucagon-like peptide-1 receptor agonists inhibit the progression of malignant pleural effusion in obese mice by regulating the metabolism of pleural effusion.","authors":"Shao, Ming-Ming; Dong, Shu-Feng; Chen, Qing-Yu; Wei, Rui-Qi; Yi, Feng-Shuang","year":2025,"journal":"Journal of translational medicine, 23(1), 886","doi":"10.1186/s12967-025-06875-8","pmid":"40781724","tags":["glp1-receptor-agonists","cancer-oncology","respiratory"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"GLP-1RA treatment reduced malignant pleural effusion volume, suppressed tumor progression, and extended survival in obese mice with lung cancer. The drug altered amino acid and nucleic acid metabolism in the pleural fluid. These effects were specific to obese mice.","whyItMatters":"Malignant pleural effusion is a severe cancer complication with few treatments. Finding that GLP-1RAs can reduce it in obese individuals opens a novel therapeutic avenue at the intersection of obesity and cancer.","specificNumbers":"Obese mice had significantly more pleural fluid than controls. GLP-1RA at 100 mcg/kg/day reduced fluid, blood glucose, and extended survival. Metabolomics: suppressed amino acid metabolism in obese MPE; enhanced purine metabolism with GLP-1RA. Minimal effects in normal-weight mice.","methodology":"HFD-induced obesity in mice. MPE model by intrapleural injection of Lewis lung carcinoma cells. Daily GLP-1RA (100 mcg/kg) vs saline. Pleural fluid collected at 2 weeks. LC-MS/MS metabolomics profiling.","limitations":"Mouse model. Lewis lung carcinoma may not represent all human cancers. Obesity-specific effect limits generalizability. Single GLP-1RA dose. Short treatment period. Metabolomic changes are associative."},{"rthcId":"RPEP-13547","title":"Research progress on oral glucagon-like peptide-1 receptor agonists in the treatment of diabetes mellitus type 2.","authors":"Shao, Qian; Xiong, Juan; Wu, Jing; Mao, Jingxin; Hu, Qing","year":2025,"journal":"Frontiers in molecular biosciences, 12, 1729904","doi":"10.3389/fmolb.2025.1729904","pmid":"41573745","tags":["glp1-receptor-agonists","metabolic-disorders"],"studyType":"narrative review","evidenceStrength":"not applicable (review)","keyFinding":"Oral GLP-1RAs work through structural modifications that resist DPP-4 degradation and activate the Gs/cAMP/PKA/EPAC pathway for glucose-dependent insulin release. They also trigger IL-6/STAT3-mediated fat browning and protect organs through AMPK, PI3K-Akt, and miRNA-regulated pathways.","whyItMatters":"Understanding the detailed molecular mechanisms of oral GLP-1 drugs helps explain their multi-organ benefits (blood sugar, weight, liver, kidney protection) and supports rational drug design.","specificNumbers":"Key pathways: AMPK, PI3K-Akt, cAMP-PKA, IL-6/STAT3. Effects: glucose-dependent insulin secretion via Gs/cAMP/PKA/EPAC; glucagon suppression via Gi/cAMP; fat browning via IL-6/STAT3; hepatoprotection via miRNA-regulated lipid metabolism; nephroprotection via sodium excretion and anti-inflammatory effects.","methodology":"Systematic integration of multi-omics research, cell/animal functional experiments, and clinical evidence on oral GLP-1RA mechanisms.","limitations":"Mechanistic review. Not all pathways are equally validated in humans. Some proposed mechanisms are based on animal data. Oral GLP-1RA clinical data are growing but still limited compared to injectables."},{"rthcId":"RPEP-13548","title":"NeoTImmuML: a machine learning-based prediction model for human tumor neoantigen immunogenicity.","authors":"Shao, Yan; Ge, Shuguang; Dong, Ruizhe; Ji, Wei; Qin, Chaoran; Wen, Pengbo","year":2025,"journal":"Frontiers in immunology, 16, 1681396","doi":"10.3389/fimmu.2025.1681396","pmid":"41200173","tags":["cancer-oncology","drug-discovery-screening"],"studyType":"computational study (tool development)","evidenceStrength":"preliminary","keyFinding":"NeoTImmuML, a weighted ensemble machine learning model combining LightGBM, XGBoost, and Random Forest, predicts tumor neoantigen immunogenicity with strong generalization. Peptide hydrophilicity and length were identified as the most important determinants.","whyItMatters":"Personalized cancer vaccines need to quickly identify which tumor mutations will trigger immune responses. This tool could speed up vaccine design by computationally pre-screening neoantigen candidates.","specificNumbers":"TumorAgDB2.0: 187,223 entries. Top algorithms: LightGBM, XGBoost, Random Forest. Key features: peptide hydrophilicity and length (SHAP analysis). Strong performance on internal and external test datasets.","methodology":"Upgraded TumorAgDB database to v2.0. Calculated peptide physicochemical properties. Evaluated 8 ML algorithms via 5-fold cross-validation. Built weighted ensemble model (NeoTImmuML). SHAP analysis for feature importance. Validated on internal and external datasets.","limitations":"Computational predictions need experimental validation. Training data may not represent all cancer types equally. Hydrophilicity and length are simplified features; real immunogenicity involves MHC binding, T cell repertoire, and tumor microenvironment."},{"rthcId":"RPEP-13549","title":"The Proteomic Analysis of Intermittent Fasting Alone or with GLP-1RA in NAFLD Rats.","authors":"Shao, Yimin; Xu, Shengya; Ma, Yuanyuan; Zhang, Junqing; Guo, Xiaohui; Zhang, Tingting; Yuan, Geheng","year":2025,"journal":"Diabetes, metabolic syndrome and obesity : targets and therapy, 18, 4073-4083","doi":"10.2147/DMSO.S550262","pmid":"41215755","tags":["glp1-receptor-agonists","liver-gi","weight-management"],"studyType":"animal study","evidenceStrength":"preliminary","keyFinding":"Intermittent fasting combined with liraglutide was superior to intermittent fasting alone for reducing weight, triglycerides, LDL, and insulin resistance in NAFLD rats. Proteomics identified GPR39 and Tmem41b as upregulated and HSD17B2 as downregulated, suggesting new therapeutic targets.","whyItMatters":"Combining lifestyle interventions (fasting) with GLP-1 drugs may offer greater liver benefits than either alone. The proteomic findings identify potential new drug targets for fatty liver disease.","specificNumbers":"ADF alone: weight loss 37.1 g, ALT decreased from 139.0 to 91.25 U/L. ADF+liraglutide: weight loss 96.15 g, lower TG (17.53 nmol/L), lower LDL (6.93 mmol/L), improved insulin resistance and NAFLD score (all p<0.05 vs ADF alone). GPR39 and Tmem41b upregulated in combination group.","methodology":"Sprague-Dawley rats on HFD for 25 weeks to establish NAFLD. Then 5 weeks of ADF alone, ADF+liraglutide, or control. Assessed liver morphology, weight, lipids, insulin sensitivity, and liver proteomics.","limitations":"Rat model. 5-week treatment is short. Small groups implied. Proteomic targets are novel and unvalidated. Alternate-day fasting may not be sustainable in humans."},{"rthcId":"RPEP-13550","title":"Inflammatory burden in dialysis patients: the role of alpha defensin.","authors":"Shapira, Maanit; Abo Aqil, Adib; Zahalka, Ameena; Abumouch, Isis; Amsalem, Naama; Abu Fanne, Rami","year":2025,"journal":"Frontiers in immunology, 16, 1718452","doi":"10.3389/fimmu.2025.1718452","pmid":"41613131","tags":["cardiovascular","kidney-renal","antimicrobial-peptides"],"studyType":"prospective cohort study","evidenceStrength":"low-moderate","keyFinding":"Hemodialysis sharply increased alpha-defensin levels (from 11,571 to 16,661 ng/mL, p=0.009) in 65% of patients. Those with post-dialysis alpha-defensin increases were more likely to develop new cardiovascular events (12.5% vs 0%) despite better lipid profiles.","whyItMatters":"Dialysis patients have extremely high cardiovascular risk. Alpha-defensin, an inflammatory peptide released during dialysis, may be a new therapeutic target for reducing atherosclerosis in this population.","specificNumbers":"37 HD patients. 55% male, median age 66.5. Alpha-defensin pre-HD: 11,571 ng/mL, post-HD: 16,661 ng/mL (p=0.009). Increased in 65% of patients. Alpha-defensin increase group: 12.5% new cardiovascular events vs 0% in decrease group (median follow-up ~5 years). Better Kt/V in decrease group (1.48 vs 1.37).","methodology":"Prospective cohort of 37 hemodialysis patients. Plasma alpha-defensin measured pre- and post-dialysis. Compared with CBC, CRP, lipids, troponin. Dialysis adequacy (Kt/V, weight change). Patients grouped by alpha-defensin change. Cardiovascular events tracked.","limitations":"Small sample (37 patients). Observational. Alpha-defensin increase may be a marker, not a cause. CRP and platelet counts did not change, suggesting alpha-defensin captures a different inflammatory pathway. Longer follow-up and larger studies needed."},{"rthcId":"RPEP-13551","title":"Liraglutide-Conjugated Poly(methyl vinyl ether-alt-maleic acid)-Coated Core-Shell Upconversion Nanoparticles for Theranostics of Diabetes.","authors":"Shapoval, Oleksandr; Engstová, Hana; Šlouf, Miroslav; Kočková, Olga; Dlasková, Andrea; Jabůrek, Martin; Halili, Aminadav; Mozheitová, Alexandra; Jirák, Daniel; Ježek, Petr; Horák, Daniel","year":2025,"journal":"ACS applied materials & interfaces, 17(30), 42863-42876","doi":"10.1021/acsami.5c11275","pmid":"40665745","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Liraglutide-conjugated nanoparticles bind GLP-1 receptors on beta cells, increase insulin secretion from isolated islets, and show 2x greater pancreatic accumulation via intramuscular vs IV injection. Receptor-mediated internalization confirmed by confocal microscopy and elemental analysis.","whyItMatters":"Targeted delivery of diabetes drugs specifically to beta cells could improve treatment efficacy while reducing systemic side effects. Combining drug delivery with imaging capabilities enables monitoring of treatment response.","specificNumbers":"","methodology":"Nanoparticle synthesis and characterization, GLP-1 receptor binding studies, insulin secretion assays on isolated Langerhans islets, biocompatibility testing, in vivo fluorescence imaging in mice, and confocal microscopy for cellular uptake.","limitations":"Preclinical mouse study. Scalability and manufacturing costs unclear. Long-term safety of rare-earth nanoparticles needs evaluation. Clinical translation pathway undefined."},{"rthcId":"RPEP-13552","title":"Severe Adverse Effects of Tirzepatide Overdose Requiring Intensive Care Unit Admission and Complex Rehabilitation.","authors":"Sharafeldin, Mahmoud; Alhamdan, Noor; Khaliq, Ayesha","year":2025,"journal":"Cureus, 17(12), e98681","doi":"10.7759/cureus.98681","pmid":"41368024","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Unsupervised rapid tirzepatide dose escalation in a 39-year-old without comorbidities caused life-threatening hypoglycemia, pancytopenia, electrolyte abnormalities, aspiration pneumonia, respiratory failure, septic shock, and multiorgan dysfunction requiring prolonged ICU stay.","whyItMatters":"As GLP-1 drugs become available through private prescribing and online pharmacies, unsupervised use and inappropriate dosing are increasing. This case demonstrates that overdose can be life-threatening even in young, healthy individuals.","specificNumbers":"","methodology":"Single case report documenting clinical course, complications, and management.","limitations":"Single case report. Cannot determine exact dose or timeline of escalation. Other contributing factors may have been present. Rare extreme case may not represent typical overdose scenarios."},{"rthcId":"RPEP-13553","title":"In Silico Pharmacogenomic Assessment of Glucagon-like Peptide-1 (GLP1) Agonists and the Genetic Addiction Risk Score (GARS) Related Pathways: Implications for Suicidal Ideation and Substance Use Disorder.","authors":"Sharafshah, Alireza; Lewandrowski, Kai-Uwe; Gold, Mark S; Fuehrlein, Brian; Ashford, John Wesson; Thanos, Panayotis K; Wang, Gene Jack; Hanna, Colin; Cadet, Jean Lud; Gardner, Eliot L; Khalsa, Jag H; Braverman, Eric R; Baron, David; Elman, Igor; Dennen, Catherine A; Bowirrat, Abdalla; Pinhasov, Albert; Modestino, Edward J; Carney, Paul R; Cortese, Rene; Fiorelli, Rossano Kepler Alvim; Schmidt, Sergio; Pollack, Aryeh R; Badgaiyan, Rajendra D; Blum, Kenneth","year":2025,"journal":"Current neuropharmacology, 23(8), 974-995","doi":"10.2174/011570159X349579241231080602","pmid":"39865816","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"STRING-MODEL analysis identified 29 relevant genes with GLP1R associations to DRD3, BDNF, CREB1, CRH, IL6, and DPP4. Enrichment analysis revealed connections between candidate genes and depressive phenotypes via dopaminergic signaling. GLP1R agonists may help addiction (hyperdopaminergia) but worsen depression/SI (hypodopaminergia).","whyItMatters":"Millions are taking GLP-1 drugs, and reports of mood changes and suicidal ideation have emerged. Understanding the genetic basis for who might be vulnerable could enable screening before prescribing and prevent rare but devastating psychiatric side effects.","specificNumbers":"","methodology":"In silico pharmacogenomic analysis using STRING-MODEL network analysis, gene enrichment analysis, and assessment of 31 refined genes related to semaglutide targets, GLP1R, and suicidal ideation, plus 10 GARS genes.","limitations":"Entirely computational (in silico)—no clinical or experimental validation. Theoretical framework needs empirical testing. Associations do not prove causation. GARS test validity is debated."},{"rthcId":"RPEP-13554","title":"Unveiling new Kv1.3 channel blockers from scorpion venom: Characterization of Meuk7-3 and in silico design of its analogs for enhanced affinity and therapeutic potential.","authors":"Shariati, Saeedeh; Mafakher, Ladan; Shirani, Maryam; Baradaran, Masoumeh","year":2025,"journal":"International journal of biological macromolecules, 319(Pt 2), 145327","doi":"10.1016/j.ijbiomac.2025.145327","pmid":"40533013","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Meuk7-3 blocks Kv1.3 via Lys19 interaction with Tyr447/797/1147/1497 in the channel pore. Three designed analogs showed improved binding stability and affinity. Meuk7-3A had the best drug-like properties and Kv1.3 binding among all tested peptides.","whyItMatters":"Kv1.3 channels on immune cells drive autoimmune inflammation. Highly selective blockers could treat diseases like MS and RA by suppressing pathogenic immune cells while sparing normal immunity—a precision approach that current immunosuppressants lack.","specificNumbers":"","methodology":"Peptide characterization from scorpion venom, molecular docking, molecular dynamics simulations, binding affinity analysis, and computational drug-likeness assessment of native and designed analogs.","limitations":"Entirely computational after initial peptide identification. No experimental electrophysiology or cell-based validation. Designed analogs need synthesis and in vitro/in vivo testing. Selectivity over other Kv channels not experimentally confirmed."},{"rthcId":"RPEP-13555","title":"Short-Term Complications of Preoperative Weight Loss Strategies in Total Knee Arthroplasty: Bariatric Surgery Versus Glucagon-Like Peptide-1 Receptor Agonists.","authors":"Sharma, Aadi; Lieu, Brigitte A; Velichala, Suhas R; Ernst, Brady; Satalich, James; Smith, Matthew; Golladay, Gregory J","year":2025,"journal":"The Journal of arthroplasty","doi":"10.1016/j.arth.2025.08.073","pmid":"40912337","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Compared to GLP-1 RA use, prior bariatric surgery before TKA was associated with significantly higher 90-day rates of periprosthetic fractures (RR 2.4, p=0.016), infections (RR 1.7, p=0.002), revisions (RR 1.9, p=0.005), cardiac events (RR 1.255, p<0.001), readmissions (RR 1.316, p=0.015), and ED visits (RR 1.2, p<0.001).","whyItMatters":"Obesity is a major risk factor for knee replacement complications, and preoperative weight loss improves outcomes. This large study provides the first comparative data between the two main weight loss strategies, strongly favoring GLP-1 drugs.","specificNumbers":"","methodology":"Retrospective review of national research network data (May 2005-Feb 2025), propensity score matching of 4,652 patients per cohort who had bariatric surgery or GLP-1 RA prescriptions within 18 months before TKA.","limitations":"Retrospective observational design. Cannot determine how much weight was lost by each method. Bariatric surgery patients may have had more severe obesity. Different time periods may introduce temporal confounding. Propensity matching cannot account for all unmeasured confounders."},{"rthcId":"RPEP-13556","title":"Effect of GLP-1 receptor agonists on prostate cancer risk reduction: a systematic review and meta-analysis.","authors":"Sharma, Nikhil; Khatib, Mahalaqua Nazli; Balaraman, Ashok Kumar; Roopashree, R; Kaur, Mandeep; Srivastava, Manish; Barwal, Amit; Prasad, G V Siva; Rajput, Pranchal; Syed, Rukshar; Sharma, Gajendra; Kumar, Sunil; Singh, Mahendra Pratap; Bushi, Ganesh; Chilakam, Nagavalli; Pandey, Sakshi; Brar, Manvinder; Mehta, Rachana; Sah, Sanjit; Gaidhane, Abhay M; Shabil, Muhammed","year":2025,"journal":"International urology and nephrology, 57(4), 1039-1049","doi":"10.1007/s11255-024-04266-4","pmid":"39495435","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Meta-analysis RR 0.72 (95% CI 0.610-0.832), indicating 28% reduced prostate cancer risk with GLP-1 RA use. Moderate heterogeneity (I²=51%). Consistent results in sensitivity analysis.","whyItMatters":"Prostate cancer is the most common cancer in men. If GLP-1 drugs truly reduce risk, the millions of men already taking them for diabetes and obesity would receive an important additional benefit, and GLP-1 drugs could potentially be used for cancer chemoprevention.","specificNumbers":"","methodology":"Systematic review and meta-analysis of PubMed, Embase, and Web of Science through July 2024. Five studies included (RCTs, cohort, case-control, observational). Random effects model. Quality assessed by Newcastle-Ottawa Scale and Cochrane Risk of Bias tool.","limitations":"Only five studies available. Moderate heterogeneity (I²=51%). Mostly observational data—cannot prove causation. Confounding by indication (diabetic patients may differ from general population). Mechanism unexplored."},{"rthcId":"RPEP-13557","title":"Radiographic Midfacial Volume Changes in Patients on GLP-1 Agonists.","authors":"Sharma, Rahul K; Vittetoe, Kelly L; Barna, Alexander J; Takkouche, Sahar; Varelas, Antonios N; Yang, Shiayin F; Stephan, Scott J; Patel, Priyesh N","year":2025,"journal":"Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery, 173(2), 360-366","doi":"10.1002/ohn.1209","pmid":"40407186","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Median total midfacial volume decreased 9%, superficial 11%, deep 7%. Superficial volume loss correlated with weight loss (rho=0.590, p=0.006). Linear regression: 7% facial volume loss per 10 kg weight loss (p=0.029). Deep volume loss did not correlate with weight.","whyItMatters":"Millions are experiencing facial changes on GLP-1 drugs but until now there was no objective measurement. This study quantifies the \"Ozempic face\" phenomenon and shows it primarily affects superficial fat, which is important for facial rejuvenation planning.","specificNumbers":"","methodology":"Retrospective cohort study at a tertiary academic center. 20 patients with GLP-1 prescriptions and head/neck CT/MR imaging before and after treatment (2017-2024). Midface volume measurements of total, superficial, and deep compartments.","limitations":"Very small sample (n=20). Retrospective design. Imaging was obtained for other clinical indications, not standardized. No control group (weight loss from other causes). Cannot distinguish drug effect from weight loss effect."},{"rthcId":"RPEP-13558","title":"Network meta-analysis of migraine therapies: balancing efficacy and safety.","authors":"Sharma, Rajat; Pandey, Ayush; Agarwal, Rachna; Tripathi, Shashank","year":2025,"journal":"Brain research, 1867, 149946","doi":"10.1016/j.brainres.2025.149946","pmid":"40972699","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CGRP antagonists: highest p-score (0.71) for reducing monthly migraine days, SMD -0.38 vs placebo. CGRP mAbs: SMD -0.35 vs placebo. Triptans: most effective for acute pain, photophobia, phonophobia, nausea. Both active classes had increased adverse events.","whyItMatters":"Migraine treatments now include multiple drug classes targeting different mechanisms. This analysis provides the first comprehensive ranking across both preventive and acute outcomes, helping clinicians make evidence-based treatment selections.","specificNumbers":"","methodology":"Frequentist network meta-analysis of 80 studies from three databases through April 2023. Six outcomes assessed. Random-effects model when I²>30%, fixed-effect when ≤30%. P-scores for ranking.","limitations":"Literature search limited to April 2023. Newer agents may not be fully represented. Heterogeneity across outcomes. Adverse event comparison across drug classes is complex due to different mechanisms and administration routes."},{"rthcId":"RPEP-13559","title":"Antibody-Free Immunopeptide Nanoconjugates for Brain-Targeted Drug Delivery in Glioblastoma Multiforme.","authors":"Sharma, Saurabh; Lee, David; Maity, Surjendu; Singh, Prabhjeet; Chadokiya, Jay; Mohaghegh, Neda; Hassani, Alireza; Kim, Hanjun; Gangarade, Ankit; Ljubimova, Julia Y; Kirane, Amanda; Holler, Eggehard","year":2025,"journal":"Bioconjugate chemistry, 36(10), 2132-2144","doi":"10.1021/acs.bioconjchem.5c00168","pmid":"40601862","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"P-12/AP-2/NCs crossed in vitro BBB, internalized in 3D GBM spheroids, mediated T cell cytotoxicity, selectively inhibited PD-1/PD-L1, increased inflammatory cytokines and T cell proliferation, showed significantly increased brain accumulation (2-6h post-injection), and were safe at low and high doses.","whyItMatters":"Glioblastoma has dismal survival (<8 months) partly because the blood-brain barrier blocks most treatments. An antibody-free, peptide-based system that delivers immunotherapy across the BBB could transform treatment of this lethal cancer.","specificNumbers":"","methodology":"Nanoconjugate synthesis with PMLA polymer, in vitro BBB-Transwell spheroid model, T cell cytotoxicity assays, PD-1/PD-L1 inhibition studies, in vivo mouse brain distribution imaging, and histopathology safety evaluation.","limitations":"Preclinical study with in vitro BBB model (not actual human BBB). No in vivo tumor efficacy or survival data. Brain accumulation shown but therapeutic concentrations not confirmed. 3D spheroid model does not replicate tumor microenvironment complexity."},{"rthcId":"RPEP-13560","title":"\"The efficacy and safety of Atogepant for migraine prophylaxis: a systematic review and meta-analysis of randomized controlled trials\".","authors":"Shaukat, Ayesha; Shakeel, Laiba; Riaz, Rumaisa; Ashraf, Saad; Akilimali, Aymar","year":2025,"journal":"BMC neurology, 25(1), 326","doi":"10.1186/s12883-025-04350-x","pmid":"40783748","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Atogepant significantly reduced MMDs vs placebo (SMD -0.39, 95% CI -0.45 to -0.33; p<0.00001; I²=0%). Also significantly reduced MHDs, monthly acute medication use days, and increased ≥50% MMD responder rates. Safety profile was acceptable.","whyItMatters":"Atogepant offers an oral CGRP-targeting option for patients who prefer pills over injections for migraine prevention. The zero heterogeneity confirms a remarkably consistent effect across diverse trial populations.","specificNumbers":"","methodology":"PRISMA-compliant meta-analysis of 6 RCTs (3,054 atogepant, 1,271 placebo). Cochrane CENTRAL, PubMed/MEDLINE, Google Scholar through July 2024. Inverse variance and Mantel-Haenszel random-effects models.","limitations":"Limited long-term data. Head-to-head comparisons with other CGRP drugs are lacking. Cost-effectiveness not assessed."},{"rthcId":"RPEP-13561","title":"Peptide-Based Functional Amyloid Hydrogel Enhances Wound Healing in Normal and Diabetic Rat Models.","authors":"Shaw, Ranjit; Patel, Komal; Chimthanawala, Niyamat M A; Sathaye, Sadhana; Maji, Samir K","year":2025,"journal":"Advanced healthcare materials, 14(9), e2403560","doi":"10.1002/adhm.202403560","pmid":"39935087","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Amyloid hydrogel achieved wound closure in 9 days (normal) and 15 days (diabetic rats). Enhanced cell migration, proliferation, collagen remodeling. Reduced inflammation while promoting angiogenesis and epidermal repair. H&E staining confirmed advanced regeneration.","whyItMatters":"Chronic wounds, especially in diabetics, are a massive healthcare burden. A peptide-based hydrogel that accelerates healing in diabetic models addresses one of the most challenging clinical problems in wound care.","specificNumbers":"","methodology":"In vitro cell migration and proliferation assays plus in vivo wound healing studies in normal and diabetic rat models with histological analysis (H&E staining).","limitations":"Rat model only. Specific peptide sequence and composition not detailed in abstract. No comparison to commercial wound dressings. Scalability and cost unknown. Human clinical trials needed."},{"rthcId":"RPEP-13562","title":"GLP-1 and GIP Changes after Sleeve Gastrectomy and Weight Regain in Adolescents. Do we need a Boost?","authors":"Shehata, Mohamed; Elhaddad, Ahmed; Mansour, Mohamed; Shehata, Sherif; El Attar, Ashraf","year":2025,"journal":"Obesity surgery, 35(10), 4087-4102","doi":"10.1007/s11695-025-08168-x","pmid":"40887512","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"264 adolescents; weight: 133→87 kg by year 2; %EWL peaked at 68%, declined to 63% by year 5. GLP-1/GIP attenuated over time. 62 patients with WR: semaglutide increased %EWL from 34% to 68% over 1 year. WR patients had larger gastric volumes and more pronounced incretin attenuation.","whyItMatters":"Weight regain after bariatric surgery is a growing concern, especially in adolescents who face decades of metabolic risk. Understanding that declining incretin hormones drive regain—and that GLP-1 drugs can reverse it—provides a targeted rescue strategy.","specificNumbers":"","methodology":"Retrospective cohort of 264 adolescents (mean age 15, 74% female) with standardized LSG, 5-year annual follow-up with weight, BMI, GLP-1, GIP measurements. WR patients (n=62) received semaglutide from year 3.","limitations":"Retrospective design. Semaglutide given without randomization or control group in WR patients. Small WR subgroup (n=62). Duration of semaglutide benefit beyond 1 year unknown."},{"rthcId":"RPEP-13563","title":"177Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) in metastatic phaeochromocytomas and paragangliomas (mPPGL): a single centre retrospective analysis of experience at an ENETS Centre of Excellence.","authors":"Shekhda, Kalyan Mansukhbhai; Armeni, Eleni; Xu, Yiwang; D'afflitto, Manfredi; Hayes, Aimee; Mandair, Dalvinder; Yu, Dominic; Quigley, Ann-Marie; Navalkissoor, Shaunak; Gnanasegaran, Gopinath; Grossman, Ashley B; Caplin, Martyn; Toumpanakis, Christos; Khoo, Bernard","year":2025,"journal":"Endocrine oncology (Bristol, England), 5(1), e250019","doi":"10.1530/EO-25-0019","pmid":"41141222","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"60% stable disease, 5% partial response, 35% progressive disease. Median PFS 24 months (overall). No grade 3/4 cytopenia or nephrotoxicity. Quality of life improved (declining symptom scores on QLQ-GINET21). 65% had ≥2 prior treatment lines.","whyItMatters":"Metastatic phaeochromocytomas and paragangliomas have limited treatment options. PRRT offers a targeted approach with a favorable safety profile, achieving disease control in most patients and improving quality of life even in heavily pretreated cases.","specificNumbers":"","methodology":"Retrospective single-center analysis of 20 patients with metastatic PCC/PGL receiving ≥2 cycles of 177Lu-DOTATATE at an ENETS Centre of Excellence. Assessed radiological, biochemical, clinical response, PFS/OS by Kaplan-Meier, and HRQoL by EORTC QLQ-GINET21.","limitations":"Retrospective single-center study. Small sample (n=20). No control group. Heterogeneous prior treatments. SDHx stratification limited by small subgroups."},{"rthcId":"RPEP-13564","title":"Mixed Neuroendocrine and Non-neuroendocrine Tumor of Pancreato-Biliary Origin Treated Successfully with Peptide Receptor Radionuclide Therapy.","authors":"Shekhda, Kalyan Mansukhbhai; Luong, Tu Vinh; Krell, Daniel; Navalkissoor, Shaunak; Paterson, Anna; Caplin, Martyn","year":2025,"journal":"Journal of gastrointestinal cancer, 56(1), 140","doi":"10.1007/s12029-025-01261-5","pmid":"40551022","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"MiNEN with 60% grade 2 NET and 30% adenocarcinoma showed no FDG-PET avidity but intense DOTATATE avidity. Failed lanreotide (6 months). Achieved partial response with 4 cycles 177Lu-DOTATATE PRRT with no significant side effects.","whyItMatters":"MiNENs have no validated treatment guidelines and poor prognosis. This case demonstrates PRRT can be effective when the neuroendocrine component predominates and shows DOTATATE avidity, potentially expanding treatment options for this rare tumor type.","specificNumbers":"","methodology":"Single case report with imaging (MRI, FDG-PET, 68Ga-DOTATATE PET), histological diagnosis, treatment with lanreotide then PRRT, and response assessment.","limitations":"Single case report. MiNENs are highly heterogeneous. Response of adenocarcinoma component unclear. Long-term outcome unknown."},{"rthcId":"RPEP-13565","title":"The Role of [177Lu] Lu-Satoreotide Tetraxetan in Somatostatin Receptor-Positive Neuroendocrine Tumors.","authors":"Shekhda, Kalyan Mansukhbhai; Navalkissoor, Shaunak","year":2025,"journal":"Seminars in nuclear medicine","doi":"10.1053/j.semnuclmed.2025.07.002","pmid":"40796453","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"SSTR antagonists bind more receptor sites and show prolonged tumor retention compared to agonists despite minimal internalization. [177Lu]Lu-satoreotide tetraxetan is the most extensively studied antagonist with accumulating preclinical and clinical evidence of efficacy and safety.","whyItMatters":"If SSTR antagonists deliver more radiation to tumors than agonists, they could significantly improve PRRT outcomes for neuroendocrine tumor patients—a meaningful advance for a therapy already considered transformative.","specificNumbers":"","methodology":"Narrative review of preclinical and clinical data on [177Lu]Lu-satoreotide tetraxetan and other SSTR antagonists for PRRT in neuroendocrine tumors.","limitations":"Many findings are preclinical or early clinical. Head-to-head comparisons with agonist-based PRRT are limited. Long-term safety of SSTR antagonist PRRT not fully characterized."},{"rthcId":"RPEP-13566","title":"Understanding the risk of diabetic retinopathy from glucagon-like peptide-1 receptor agonists: a Mendelian randomization study and systematic review of European populations.","authors":"Shen, Baixuan; Wang, Wanying; Guo, Yuanhui; Chen, Zilong; Liu, Chuanxin; Huang, Jiarui; Li, Ying","year":2025,"journal":"Diabetology & metabolic syndrome, 17(1), 345","doi":"10.1186/s13098-025-01878-3","pmid":"40830891","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"MR: OR 0.59 (95% CI 0.39-0.89, p=0.011); SMR: OR 0.48 (95% CI 0.27-0.86, p=0.013). Systematic review: GLP-1RA reduced DR incidence vs insulin therapy. Results from discovery and validation (FinnGen) cohorts combined via meta-analysis.","whyItMatters":"Diabetic retinopathy is a leading cause of blindness. If GLP-1 drugs protect against it beyond just glucose control, this adds an important reason to prescribe them for diabetic patients, especially those at risk for eye complications.","specificNumbers":"","methodology":"Two-sample Mendelian randomization using 9 cis-eQTL SNPs as genetic instruments, with SMR validation. Discovery cohort from GWAS catalog + FinnGen validation. Plus systematic review of 3 cohort studies.","limitations":"European populations only. Limited to genetic proxy—does not capture dose-response. Only 3 studies in systematic review. Inconsistent results vs non-insulin agents."},{"rthcId":"RPEP-13567","title":"GLP-1 receptor agonist exendin-4 suppresses food intake by inhibiting hindbrain orexigenic NPY neurons.","authors":"Shen, Jiayi; Wang, Mengtian; Pang, Guodong; Zhang, Yan; Zhang, Jian; Shi, Yuyan; Liu, Ji; Zhan, Cheng","year":2025,"journal":"American journal of physiology. Endocrinology and metabolism, 328(5), E661-E674","doi":"10.1152/ajpendo.00528.2024","pmid":"40126941","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Exendin-4 inhibits NTS NPY neurons indirectly via GABAb receptors by augmenting presynaptic GABA release. Chemogenetic activation of NTS NPY neurons counteracted exendin-4 anorexia. Chemogenetic inhibition of NTS NPY neurons mimicked exendin-4 eating suppression.","whyItMatters":"Understanding exactly how GLP-1 drugs suppress appetite in the brain could lead to more targeted weight loss drugs with fewer side effects and help explain why some people respond better than others to GLP-1 therapy.","specificNumbers":"","methodology":"Ex vivo electrophysiological recordings from NTS NPY neurons, chemogenetic (DREADD) activation and inhibition experiments, food intake measurements in mice.","limitations":"Mouse study—circuits may differ in humans. Ex vivo recordings may not fully replicate in vivo physiology. Only exendin-4 tested; other GLP-1 agonists may differ. Chemogenetic tools have limitations."},{"rthcId":"RPEP-13568","title":"GLP-1 Receptor Agonist Use and Weight Change in Patients With Breast Cancer.","authors":"Shen, Sherry; Bethina Liu Md; Chad Fanti Md; Maria Bromberg Mph; Yuan Chen PhD; Cassandra Chang; Neil M Iyengar Md","year":2025,"journal":"Oncology (Williston Park, N.Y.), null(7), 294-296","doi":"10.46883/2025.25921046","pmid":"40834286","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Mean weight loss: -2.9 kg (95% CI -4.1 to -1.7) at 6 months, -4.2 kg (95% CI -5.5 to -2.9) at 12 months, -5% body weight at 12 months. No significant predictors of ≥5% weight loss in uni/multivariable analyses.","whyItMatters":"Obesity worsens breast cancer outcomes, and many cancer treatments cause weight gain. Finding that GLP-1 drugs produce meaningful weight loss during breast cancer treatment, without interference from cancer characteristics, supports their integration into oncology care.","specificNumbers":"","methodology":"Retrospective cohort of 75 breast cancer patients with GLP-1 RA prescriptions and follow-up weight data. Linear mixed effects model with random intercept for baseline weight.","limitations":"Retrospective, no control group. Small sample (n=75). Most patients had diabetes (GLP-1 prescribed for metabolic indications). Weight loss modest compared to non-cancer populations. Potential survivor bias."},{"rthcId":"RPEP-13569","title":"The Expanding Scope of GLP-1 Receptor Agonists: Six Uses Beyond Diabetes.","authors":"Sheth, Kyle; Kim, Stephanie; Porterfield, Laura; Virani, Salim S; Wadhwani, Shikha; Vaughan, Elizabeth M","year":2025,"journal":"Current atherosclerosis reports, 27(1), 76","doi":"10.1007/s11883-025-01319-6","pmid":"40736924","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Six applications beyond T2DM: obesity (strong evidence), cardiovascular protection (strong), kidney protection (strong), obstructive sleep apnea (emerging), MASLD (emerging), and substance use disorders (preliminary/variable). Cost and side effects limit access.","whyItMatters":"Understanding the full therapeutic scope of GLP-1 drugs helps clinicians maximize benefit for patients with multiple conditions, potentially treating several problems with one medication.","specificNumbers":"","methodology":"Narrative review of clinical evidence for GLP-1RA applications beyond diabetes.","limitations":"Narrative review without systematic methodology. Evidence strength varies widely across the six indications. Cost and access barriers not quantified."},{"rthcId":"RPEP-13570","title":"Immunotherapy targeting a leader sequence cathepsin G-derived peptide.","authors":"Shi, Chunhua; Tian, Ze; Yan, Jun; Zhang, Mao; Sukhumalchandra, Pariya; Chang, Edward; Yang, Guojun; You, Junping; Cui, Meng; Shi, Qing; Kerros, Celine; Philips, Anne; Qiao, Na; Torikai, Hiroki; Patchametla, Sathvik; Sergeeva, Anna; St John, Lisa; He, Helen; Wiederschain, Dmitri; Lee, Benjamin H; Paulus, Geraldine L C; Zha, Dongxing; Molldrem, Jeffrey; Alatrash, Gheath","year":2025,"journal":"Leukemia, 39(4), 888-898","doi":"10.1038/s41375-025-02520-x","pmid":"39939820","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CG1/A2xCD3 showed high binding affinity to CG1/HLA-A2, potent killing of HLA-A2+ primary AML and cell lines in vitro and in vivo, tumor- and antibody-dependent T cell activation and cytokine secretion, and no activity against normal bone marrow.","whyItMatters":"AML has limited treatment options and high relapse rates. Targeting peptide-HLA complexes with bispecific antibodies offers a precision approach that can distinguish leukemia from normal blood cells, potentially reducing treatment toxicity.","specificNumbers":"","methodology":"Antibody engineering, binding affinity assays, in vitro cytotoxicity against primary AML and cell lines, in vivo xenograft models, T cell activation/cytokine assays, and normal bone marrow safety testing.","limitations":"Restricted to HLA-A2+ patients (~40-50% of populations). Single peptide target. Preclinical data only. Safety in humans not established. Potential for on-target off-tumor toxicity needs evaluation."},{"rthcId":"RPEP-13571","title":"Liraglutide ameliorates intrauterine adhesion by inhibiting NF-κb phosphorylation and reducing epithelial-mesenchymal transition.","authors":"Shi, Jie; Xu, Weicong; Yang, Tao; Bayijuma, Ayana; Huang, Yujie; Zhou, Yunxiao","year":2025,"journal":"Experimental cell research, 451(2), 114708","doi":"10.1016/j.yexcr.2025.114708","pmid":"40784419","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Liraglutide reduced endometrial inflammation, collagen fibrosis, and EMT in IUA rat and human organoid models. NF-κB identified as a direct binding target of liraglutide. Blocking liraglutide-NF-κB interaction attenuated all protective effects.","whyItMatters":"IUA causes infertility and has limited treatment options. Discovering that a widely available GLP-1 drug can treat uterine scarring through a novel mechanism (direct NF-κB binding) could provide a new off-label therapeutic option.","specificNumbers":"","methodology":"Rat IUA model (mechanical damage), human endometrial organoids (RU486-induced), primary human cells (TGF-β-treated), H&E/Masson staining, immunohistochemistry, Western blot, SuperPred target prediction, and cellular thermal shift assay.","limitations":"Preclinical study. No human clinical trial data. The direct NF-κB binding mechanism is novel and needs independent validation. Doses used may not reflect clinical GLP-1 dosing."},{"rthcId":"RPEP-13572","title":"Bee venom alleviates isoproterenol-induced cardiac hypertrophy via JAK2/NF-κB signaling cascade.","authors":"Shi, Peiying; Han, Shuo; Sun, Yang; Li, Mengmeng; Xu, Xueling","year":2025,"journal":"Tissue & cell, 97, 103077","doi":"10.1016/j.tice.2025.103077","pmid":"40795597","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Melittin identified as dominant BV component. BV prevented ECG and echo abnormalities, reversed morphological and histological heart changes, downregulated hypertrophy markers (β-MHC, ANP, BNP), ACE, and IL-1β, and inhibited JAK2/NF-κB signaling in ISO-induced cardiac hypertrophy.","whyItMatters":"Cardiac hypertrophy progresses to heart failure, a leading cause of death. Bee venom peptides, particularly melittin, offer a natural peptide-based therapeutic approach targeting both the renin-angiotensin system and inflammatory pathways simultaneously.","specificNumbers":"","methodology":"UPLC-Q/TOF-MS for BV characterization, isoproterenol-induced cardiac hypertrophy in mice (in vivo) and cardiomyocytes (in vitro), ECG, echocardiography, histopathology, network pharmacology, Western blot, and RT-qPCR.","limitations":"Preclinical study in mice. Bee venom is a complex mixture—clinical translation requires purified melittin. Safety profile of repeated melittin administration needs evaluation. ISO-induced hypertrophy is a simplified model."},{"rthcId":"RPEP-13573","title":"Intranasal and Intravenous Sequential Administration of Survivin Peptide-CpG Nanovaccines Elicits Potent Immunity Toward Glioblastoma.","authors":"Shi, Yan; Sun, Yinping; Zhao, Songsong; Sun, Zhiwei; Xia, Mingyu; Zhong, Zhiyuan; Meng, Fenghua","year":2025,"journal":"Advanced materials (Deerfield Beach, Fla.), 37(33), e2420630","doi":"10.1002/adma.202420630","pmid":"40489066","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Sequential intranasal/IV administration with anti-CTLA-4: 43% complete GBM regression. Intranasal route bypassed BBB via olfactory bulb and trigeminal nerve. Enhanced DC uptake and activation. Robust local and systemic anti-GBM immunity.","whyItMatters":"GBM is virtually incurable with <8 months median survival. A nasal spray vaccine that delivers immunotherapy directly to brain tumors could revolutionize treatment by overcoming the blood-brain barrier—the main obstacle to effective brain cancer therapy.","specificNumbers":"","methodology":"Nanovaccine synthesis (survivin peptide-CpG polymersomes), in vitro BBB penetration and DC activation, orthotopic murine GL261 GBM model, biodistribution imaging, combination with anti-CTLA-4.","limitations":"Mouse model only (GL261). Single tumor model tested. Combination with checkpoint inhibitor needed for optimal efficacy. Human BBB anatomy may differ. Scalability and GMP manufacturing undefined."},{"rthcId":"RPEP-13574","title":"Systematic All-Hydrocarbon Stapling Analysis for Cecropin A Generates a Potent and Stable Antimicrobial Peptide.","authors":"Shi, Yejiao; Luo, Gan; Zhen, Borui; Liu, Zhinan; Chen, Sumeng; Wang, Zhe; Lu, Wuyuan; Hu, Honggang; Li, Xiang","year":2025,"journal":"Journal of medicinal chemistry, 68(6), 6372-6385","doi":"10.1021/acs.jmedchem.4c02852","pmid":"40062552","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"27 stapled cecropin A derivatives created. CEC-2-9 identified as optimal: enhanced antibacterial potency, increased helicity and stability, decreased hemolysis, improved in vivo efficacy in peritonitis sepsis model.","whyItMatters":"Antimicrobial resistance demands new antibiotics. Stapling technology transforms natural antimicrobial peptides from unstable lab curiosities into stable, potent drug candidates—this systematic approach could be applied to other AMPs.","specificNumbers":"","methodology":"Systematic (i, i+4) all-hydrocarbon stapling, antimicrobial activity testing, hemolytic activity assays, membrane damage studies, proteolytic stability assessment, and murine peritonitis sepsis treatment model.","limitations":"Single optimal variant from 27 tested—further optimization possible. Specific bacterial spectrum not detailed. Manufacturing scalability unclear. Safety beyond hemolysis needs characterization."},{"rthcId":"RPEP-13575","title":"In Silico Exploration of Therapeutics for GLP-1 Receptor Agonist-Induced Nausea and Their in Vivo Validation in Mice.","authors":"Shibui, Norihiro; Suzuki, Takahide; Yamamoto, Hiroki; Shirakawa, Hisashi; Kaneko, Shuji; Yamamoto, Kouichi; Nagayasu, Kazuki","year":2025,"journal":"Biological & pharmaceutical bulletin, 48(8), 1233-1238","doi":"10.1248/bpb.b25-00077","pmid":"40866246","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"FAERS analysis: gabapentin and acetaminophen significantly lowered nausea events in GLP-1-treated patients. Mouse validation: exenatide induced dose-dependent pica (nausea); gabapentin co-treatment significantly decreased exenatide-induced pica without affecting food intake.","whyItMatters":"Nausea is the #1 reason patients discontinue GLP-1 drugs. Finding an effective co-medication like gabapentin could dramatically improve adherence and allow more patients to benefit from these transformative drugs.","specificNumbers":"","methodology":"Retrospective analysis of FDA AERS database for drug combinations reducing GLP-1-associated nausea. In vivo validation using exenatide-induced pica behavior in mice with gabapentin co-administration.","limitations":"FAERS data is observational and subject to reporting biases. Mouse pica is a proxy for nausea, not direct measurement. Only gabapentin validated in vivo; acetaminophen needs confirmation. Only exenatide tested in mice."},{"rthcId":"RPEP-13576","title":"Efficacy and Safety of Tirzepatide and Semaglutide for Obesity Management: A Real-World Comparison.","authors":"Shil, Kishore Kumar; Hira, Ananda D; Bakchi, Sudipta; Paul, Susanta K; Hossain, Mahmud; Ghosh, Debasish K","year":2025,"journal":"Cureus, 17(12), e98858","doi":"10.7759/cureus.98858","pmid":"41523559","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tirzepatide: -8.53 kg vs semaglutide: -6.85 kg (p=0.033). 89% achieved ≥5% weight loss; 33% achieved ≥10%. Tirzepatide had higher rates in both thresholds. Lifestyle interventions most enhanced tirzepatide. GI adverse events more frequent with tirzepatide.","whyItMatters":"Real-world evidence from South Asian populations is critical since most GLP-1 trial data comes from Western populations. This study confirms tirzepatide's superiority in a demographic with distinct metabolic profiles and obesity patterns.","specificNumbers":"","methodology":"Retrospective observational study of 100 adults from three tertiary centers in Bangladesh (58 tirzepatide, 42 semaglutide) with ≥3 months treatment. Demographics, weight, adverse events collected via structured questionnaire.","limitations":"Retrospective, non-randomized. Small sample (n=100). Baseline BMI was significantly different between groups. Young, predominantly female cohort may not be representative. Short follow-up for some patients."},{"rthcId":"RPEP-13577","title":"GLP-1R agonist promotes proliferation of neuroendocrine neoplasm cells expressing GLP-1 receptors.","authors":"Shilyansky, Jonathan S; Chan, Casandro J; Xiao, Sophia; Gribovskaja-Rupp, Irena; Quelle, Dawn E; Howe, James R; Dillon, Joseph S; Ear, Po Hien","year":2025,"journal":"Surgery, 179, 108943","doi":"10.1016/j.surg.2024.09.052","pmid":"39665969","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"3 of 6 NET cell lines expressed high GLP-1R. Semaglutide increased GOT1 growth 19%, NT-3 growth 22% in vitro. In vivo: semaglutide increased GOT1 xenograft tumor volume by 72%. GLP-1R expression correlated with growth response.","whyItMatters":"As millions take semaglutide for weight loss and diabetes, patients with undiagnosed or known neuroendocrine tumors could be at risk of accelerated tumor growth. This is the first systematic study demonstrating this concern with in vivo evidence.","specificNumbers":"","methodology":"GLP-1R quantification by qPCR, immunofluorescence, and Western blot in 6 NET cell lines. Semaglutide treatment with cell viability assays. In vivo GOT1 xenograft model with semaglutide treatment and tumor volume measurement.","limitations":"Preclinical study. Only one xenograft model. Dose used in mice may not reflect human clinical doses. NET heterogeneity means some tumors may not respond. No human patient data."},{"rthcId":"RPEP-13578","title":"Externally Triggered Activation of Nanostructure-Masked Cell-Penetrating Peptides.","authors":"Shim, Gayong","year":2025,"journal":"Molecules (Basel, Switzerland), 30(15)","doi":"10.3390/molecules30153205","pmid":"40807380","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"DNA nanoflower structures (150-250 nm) masked CPP activity under physiological conditions. Cold plasma treatment disrupted DNA masking and restored peptide function. Fluorescence recovery, cellular uptake, and cytotoxicity all controllable by plasma activation in 2D and 3D models.","whyItMatters":"Uncontrolled cell penetration is the main limitation of CPP-based drug delivery. This system solves it by providing an external \"on switch\" that activates the peptide only where and when needed, potentially reducing side effects of peptide-delivered drugs.","specificNumbers":"","methodology":"DNA nanoflower synthesis and TEM characterization, structural/functional analysis, fluorescence recovery assays, cellular uptake studies, cytotoxicity measurements in monolayer and 3D spheroid models, cold plasma activation.","limitations":"Proof of concept only—no in vivo data. Cold plasma has limited tissue penetration depth. Clinical applicability of external plasma activation needs evaluation. Manufacturing scalability unclear."},{"rthcId":"RPEP-13579","title":"Modulation of Bifidobacterium by HD5 during weaning is associated with high abundance in later life.","authors":"Shimizu, Yu; Yokoi, Yuki; Ohira, Shuya; Izumi, Hirohisa; Kawakami, Satomi; Ihara, Miu; Tabata, Fuka; Takeda, Yasuhiro; Kimura, Takashi; Nakamura, Koshi; Tamakoshi, Akiko; Ayabe, Tokiyoshi; Nakamura, Kiminori","year":2025,"journal":"Communications medicine, 5(1), 250","doi":"10.1038/s43856-025-00977-6","pmid":"40595013","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"HD5 secretion positively correlated with Bifidobacterium abundance during weaning. High weaning-period Bifidobacterium predicted Bifidobacterium-rich microbiota at age 3. HD5 selectively kills pathogens while sparing beneficial bacteria like Bifidobacterium.","whyItMatters":"Understanding how innate immune peptides shape lifelong gut health could guide strategies to optimize infant nutrition and prevent microbiome-related diseases. HD5 may be a key factor in establishing the beneficial gut bacteria that protect health throughout life.","specificNumbers":"","methodology":"Longitudinal cohort study (SMILE Iwamizawa) of 33 children with 148 serial fecal samples from 3-5 days to 3 years. Microbiota composition by 16S rRNA sequencing, HD5 levels by ELISA.","limitations":"Small cohort (33 children) from one Japanese city. Correlation does not prove causation. Confounders like breastfeeding, diet, and antibiotic use may influence results. HD5 mechanism inferred from prior in vitro data."},{"rthcId":"RPEP-13580","title":"Distinct Gut-Brain Axis Dysregulation in Episodic Versus Chronic Migraine: Insights from NTG-Induced Mouse Models.","authors":"Shin, Dae-Chul; Jung, Harry; Park, Songyi; Song, Dan-Gyeong; Lee, Sang-Hwa; Sohn, Jong-Hee","year":2025,"journal":"International journal of molecular sciences, 26(21)","doi":"10.3390/ijms262110493","pmid":"41226532","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CM vs EM: CM showed shortened colon length, elevated gut CGRP, increased inflammatory cytokines, and enrichment of T cells, Tregs, and macrophages in distal colon. EM showed increased dendritic and B cell populations. Both reduced food intake and body weight.","whyItMatters":"CGRP is already the target of major migraine drugs (erenumab, fremanezumab). Finding that CGRP is elevated in the gut during chronic migraine—and that GI damage differs between migraine types—suggests CGRP-targeting drugs may have gut-protective benefits and that gut health could influence migraine management.","specificNumbers":"","methodology":"NTG-induced mouse models of EM (single injection, N=15) and CM (repeated injections over 9 days, N=15). GI tissue analysis for morphology, cytokines, CGRP levels, and immune cell profiling.","limitations":"Mouse model—NTG-induced migraine is a simplified model. CGRP elevation in gut may be a consequence rather than cause of GI damage. Small group sizes. No therapeutic intervention tested."},{"rthcId":"RPEP-13581","title":"Prognostic value of interim [68Ga]Ga-DOTA-TOC PET/CT in patients with neuroendocrine tumour who underwent peptide receptor radionuclide therapy.","authors":"Shin, Eonwoo; Kim, Yong-Il; Yoo, Changhoon; Shin, Yeokyeong; Ryoo, Baek-Yeol; Lee, Dong Yun; Ryu, Jin-Sook","year":2025,"journal":"European radiology, 35(5), 2559-2568","doi":"10.1007/s00330-024-11116-5","pmid":"39436411","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"High ΔWTV (≥-10%): HR 3.053 (p=0.049); high ΔTRE (≥-21%): HR 3.567 (p=0.028) for shorter PFS. Both remained significant in multivariate analysis adjusted for WHO grade (HR 3.345 and 3.894). 66.7% of patients experienced progression.","whyItMatters":"PRRT is expensive and involves radiation exposure. Early identification of non-responders after 2 cycles could guide decisions about continuing PRRT versus switching to alternative therapies, improving both outcomes and resource utilization.","specificNumbers":"","methodology":"Retrospective analysis of 24 NET patients with basal and interim (after 2 PRRT cycles) 68Ga-DOTA-TOC PET/CT. Kaplan-Meier survival analysis, log-rank tests, and Cox proportional hazards regression.","limitations":"Small sample (n=24). Retrospective single-center design. Cut-off thresholds need prospective validation. PFS used as endpoint rather than overall survival."},{"rthcId":"RPEP-13582","title":"Glucagon‑like peptide‑1 receptor agonists in multiple sclerosis: therapeutic promise, challenges, and future directions.","authors":"Shirani, Afsaneh; Stuve, Olaf","year":2025,"journal":"Expert opinion on investigational drugs, 34(11), 929-941","doi":"10.1080/13543784.2025.2587277","pmid":"41196232","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In EAE and demyelination models: reduced oxidative stress, preserved axons, suppressed microglial/astrocytic activation, promoted remyelination. Early MS patient data: well-tolerated, metabolic benefits, no disease exacerbation. Diabetic cohorts: reduced neurological impairment and dementia incidence.","whyItMatters":"MS has no cure, and current therapies mainly suppress immune attacks without repairing nerve damage. If GLP-1 drugs can both protect nerves and promote repair, they could address a critical unmet need—especially since they are already widely available and well-characterized.","specificNumbers":"","methodology":"Narrative review synthesizing preclinical (EAE and toxin-induced demyelination models) and early clinical/observational evidence for GLP-1RAs in MS.","limitations":"No published RCTs in MS. Preclinical models are simplified versions of human MS. Observational data subject to confounding. Drug availability and cost are practical barriers."},{"rthcId":"RPEP-13583","title":"Efficacy of GLP-1 receptor agonists on obesity and metabolic profile in patients with inflammatory bowel disease: a systematic review and meta-analysis.","authors":"Shirmard, Fatemeh Ojaghi; Pourfaraji, Seyed Morteza; Omouri-Kharashtomi, Mahyaar; Amani, Arash","year":2025,"journal":"BMC gastroenterology, 25(1), 878","doi":"10.1186/s12876-025-04496-5","pmid":"41275083","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Pooled weight change: -5.71 kg (95% CI -9.56 to -1.86, p=0.01; I²=78%). Semaglutide subgroup: -5.59 kg (p=0.03; I²=80%). BMI change: -2.18 kg/m² (p<0.01; I²=81.1%). Evidence certainty: Low (weight) to Very Low (other outcomes).","whyItMatters":"IBD patients increasingly face obesity but have unique concerns—GI side effects of GLP-1 drugs may overlap with IBD symptoms, and effects on intestinal inflammation are unknown. This first meta-analysis provides preliminary safety and efficacy data for this population.","specificNumbers":"","methodology":"Systematic review and meta-analysis of PubMed, Embase, Scopus, Web of Science through October 2025. PROSPERO registered. 8 retrospective cohort studies, 1,236 patients. Random-effects model. GRADE assessment.","limitations":"All 8 studies were retrospective. High heterogeneity. Low to very low evidence certainty (GRADE). IBD-specific outcomes (disease flares, inflammation) not well-reported. Small secondary outcome analyses."},{"rthcId":"RPEP-13584","title":"Cardiovascular and renal outcomes of dual combination therapies with glucagon-like peptide-1 receptor agonists and sodium-glucose transport protein 2 inhibitors: a systematic review and meta-analysis.","authors":"Shokravi, Arveen; Seth, Jayant; Mancini, G B John","year":2025,"journal":"Cardiovascular diabetology, 24(1), 370","doi":"10.1186/s12933-025-02900-8","pmid":"41029853","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"RCTs: no interaction (p>0.05 all outcomes)—GLP-1RA benefits consistent with/without SGLT2i. Observational: combo vs SGLT2i mono: MACE HR 0.59, all-cause mortality HR 0.57, MI HR 0.73, stroke HR 0.72, HF HR 0.71. Combo vs GLP-1RA mono: CV mortality HR 0.35, all-cause mortality HR 0.59, renal HR 0.43.","whyItMatters":"This provides the strongest evidence to date that combining GLP-1 and SGLT2 drugs saves more lives and prevents more cardiovascular and kidney events than either drug alone—supporting dual therapy as a new standard for high-risk T2D patients.","specificNumbers":"","methodology":"Systematic search of MEDLINE/Embase. 4 post hoc RCT analyses + 10 observational studies. Random-effects meta-regression (RCTs) and meta-analysis (observational) for cardiorenal outcomes.","limitations":"RCT evidence is from post hoc analyses, not dedicated combination trials. Observational data subject to confounding and selection bias. Heterogeneity across studies. No data on triple combination with finerenone."},{"rthcId":"RPEP-13585","title":"Effectiveness of SGLT2 inhibitors, incretin-based therapies, and finerenone on cardiorenal outcomes: a meta-analysis and network meta-analysis.","authors":"Shokravi, Arveen; Seth, Jayant; Lu, Nelson; Mancini, G B John","year":2025,"journal":"Cardiovascular diabetology. Endocrinology reports, 11(1), 37","doi":"10.1186/s40842-025-00248-2","pmid":"41354946","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"NMA: SGLT2i reduced HF hospitalization and kidney outcomes more than incretin therapies in T2D+ASCVD/high CV risk and CKD. Incretin therapies uniquely reduced HF events in HFpEF with obesity. Both classes reduced MACE, CV mortality, all-cause mortality, MI, and stroke in T2D+ASCVD. SGLT2i benefits extended to acute HF and post-MI.","whyItMatters":"Clinicians need to know which drug to prescribe first for cardiorenal protection. This analysis suggests SGLT2 inhibitors should be prioritized for heart failure and kidney protection, while GLP-1 drugs may be preferred for obese HFpEF patients.","specificNumbers":"","methodology":"Systematic search of MEDLINE/CENTRAL (Jan 2023-Apr 2025) plus prior meta-analyses. 33 RCTs included. Random-effects meta-analysis plus network meta-analysis comparing drug classes.","limitations":"Network meta-analysis relies on indirect comparisons (no head-to-head trials). Population overlap across included trials. Tirzepatide grouped with GLP-1 drugs. Subgroup analyses may be underpowered."},{"rthcId":"RPEP-13586","title":"Registered clinical trials targeting type 2 diabetes remission with pharmacological interventions.","authors":"Shoung, Nicholas; Carette, Claire; Rassy, Nathalie; Phan, Aurélie; Greenfield, Jerry R; Hu, Frank B; Rives-Lange, Claire; Czernichow, Sébastien","year":2025,"journal":"Scientific reports, 15(1), 18363","doi":"10.1038/s41598-025-00080-9","pmid":"40419497","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"34 trials identified; 70.6% non-industry funded; 88.2% targeted T2D diagnosed ≤6 years; 56% used combination therapy (metformin + insulin + GLP-1); 35.3% lacked specific remission criteria. GLP-1RAs and GIP analogs recommended for future trials.","whyItMatters":"T2D remission was once thought impossible without surgery. Identifying that GLP-1-based pharmacotherapy is central to most remission trials signals a paradigm shift toward medication-induced diabetes reversal.","specificNumbers":"","methodology":"Systematic search of ClinicalTrials.gov, WHO ICTRP, and EU CTIS (March 2024). Registered as PROSPERO CRD42024511198.","limitations":"Mapping study of trial registrations, not outcomes. Many trials ongoing or unpublished. Lack of standardized remission criteria limits comparison. Publication bias possible."},{"rthcId":"RPEP-13587","title":"Antimicrobial peptides: a promising frontier to combat antibiotic resistant pathogens.","authors":"Shriwastav, Shalini; Kaur, Narinder; Hassan, Mahmudul; Ahmed Mohammed, Shakeel; Chauhan, Samrat; Mittal, Divya; Aman, Shahbaz; Bibi, Ayesha","year":2025,"journal":"Annals of medicine and surgery (2012), 87(4), 2118-2132","doi":"10.1097/MS9.0000000000003106","pmid":"40212220","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"AMPs combat drug resistance through membrane permeabilization, intracellular process alteration, biofilm inhibition, and immune modulation. These multiple mechanisms make resistance development challenging. AMPs are effective against bacteria, viruses, fungi, and cancer cells.","whyItMatters":"Antibiotic resistance is projected to cause 10 million deaths annually by 2050. AMPs offer a fundamentally different approach to fighting infections that could complement or replace failing antibiotics.","specificNumbers":"","methodology":"Narrative review of AMP mechanisms, broad-spectrum activity, and therapeutic potential against drug-resistant pathogens.","limitations":"Narrative review without systematic methodology. Clinical translation of AMPs has been slow due to stability, cost, and delivery challenges. Not all AMPs are suitable for systemic use."},{"rthcId":"RPEP-13588","title":"Evaluation of Additive Neuroprotective Effect of Combination Therapy for Parkinson's Disease Using In Vitro Models.","authors":"Shtilbans, Alexander; Esneault, Elise; Simon, Florian; Mazzulli, Joseph R; Quiriconi, Drew J; Rom, Dror; Reintsch, Wolfgang E; Krahn, Andrea I; Durcan, Thomas M","year":2025,"journal":"Antioxidants (Basel, Switzerland), 14(4)","doi":"10.3390/antiox14040396","pmid":"40298667","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Out of 44 combinations of 9 drugs, sodium phenylbutyrate + exenatide + tauroursodeoxycholic acid uniquely improved 4 endpoints (neurite length, branch points, live neurons, neurofilament). Tested in wild-type iPSC-derived neurons, idiopathic PD patient cells, and alpha-synuclein triplication line.","whyItMatters":"No current treatment slows Parkinson's disease progression. This study shows that combining drugs targeting different PD mechanisms—including the GLP-1 drug exenatide—can achieve neuroprotection superior to any single agent, potentially forming the basis for the first disease-modifying PD therapy.","specificNumbers":"","methodology":"Drug repurposing screen: 44 combinations of 9 drugs in iPSC-derived human dopaminergic neurons (wild-type + PD patient-derived + alpha-synuclein triplication) treated with MPP+. Metrics: neurite length, branch points, live neurons, neurofilament, inflammatory cytokines.","limitations":"In vitro study—cell models cannot fully replicate human PD. MPP+ toxin model represents only one PD mechanism. Optimal doses and drug interactions in vivo unknown. Only 44 of many possible combinations tested."},{"rthcId":"RPEP-13589","title":"New Aspects of Protein Biosynthesis Inhibition by Proline-Rich Antimicrobial Peptides.","authors":"Shulenina, Olga V; Tolstyko, Eugene A; Konevega, Andrey L; Paleskava, Alena","year":2025,"journal":"Biochemistry. Biokhimiia, 90(11), 1536-1552","doi":"10.1134/S0006297925602394","pmid":"41354068","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Two classes of PrAMP mechanisms identified: Class I blocks elongation (A-site tRNA interference, P-site CCA-end disruption), Class II disrupts termination, ribosome release, and 50S assembly. New rumidicin family with Trp-Phe dyad enhances activity. Multiple binding sites on ribosomes for Class II.","whyItMatters":"PrAMPs have the highest safety profiles among antimicrobial peptides because they target ribosomes (like many antibiotics) rather than membranes. Understanding their precise mechanisms enables rational design of more potent peptide antibiotics.","specificNumbers":"","methodology":"Review of structural studies (cryo-EM, X-ray crystallography) and functional analyses of PrAMP-ribosome interactions.","limitations":"Mechanistic review of structural data; clinical development of PrAMP-based drugs is still early. Most data from in vitro ribosome studies. In vivo efficacy and pharmacokinetics need development."},{"rthcId":"RPEP-13590","title":"Neuropeptide Y modulates the electrical activity of subfornical organ neurons.","authors":"Shute, Lauren; Fry, Mark","year":2025,"journal":"Current research in neurobiology, 8, 100149","doi":"10.1016/j.crneur.2025.100149","pmid":"40308261","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"NPY depolarized 16% and hyperpolarized 26% of SFO neurons (n=31). EC50: 3.9 nM (depolarizing), 3.5 nM (hyperpolarizing). Y5: predominantly hyperpolarizing; Y1/Y2: mixed. Mechanisms: increased voltage-gated K+ current (hyperpolarization), persistent Na+ current shift (depolarization).","whyItMatters":"The SFO is a critical brain integration center for metabolic signals, and NPY is a major appetite-regulating peptide. Establishing that NPY directly acts on SFO neurons reveals a new pathway by which this neuropeptide influences energy balance and cardiovascular regulation.","specificNumbers":"","methodology":"Patch clamp electrophysiology on dissociated rat SFO neurons. Dose-response studies, receptor-selective agonists (Y1, Y2, Y5), current-clamp and voltage-clamp recordings.","limitations":"Dissociated rat neurons may not fully represent in vivo circuit properties. Only one neuropeptide tested. Functional consequences for appetite or cardiovascular regulation not assessed. Rat physiology may differ from human."},{"rthcId":"RPEP-13591","title":"Evaluating semaglutide + LAI-287 (IcoSema) for the treatment of diabetes mellitus type II.","authors":"Siamashvili, Maka; Davis, Stephen N","year":2025,"journal":"Expert opinion on pharmacotherapy, 26(1), 1-7","doi":"10.1080/14656566.2024.2436593","pmid":"39629799","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"IcoSema: glycemic efficacy non-inferior to glargine+aspart; similar hypoglycemia risk; significant body weight reduction (vs weight gain with insulin); once-weekly convenience; favorable safety profile.","whyItMatters":"Complex insulin regimens are a major barrier to diabetes management. Reducing from multiple daily injections to one weekly injection while maintaining control and adding weight loss could dramatically improve treatment adherence and quality of life.","specificNumbers":"","methodology":"Narrative review of insulin icodec, semaglutide, and IcoSema clinical development and key trials.","limitations":"Review article based on registration trials. Long-term real-world data limited. GI side effects from semaglutide component remain a concern. Cost and insurance coverage unknown."},{"rthcId":"RPEP-13592","title":"Macronutrient, Micronutrient Supplementation and Monitoring for Patients on GLP-1 Agonists: Can We Learn from Metabolic and Bariatric Surgery?","authors":"Sibal, Rhea; Balamurugan, G; Langley, Jasmine; Graham, Yitka; Mahawar, Kamal","year":2025,"journal":"Nutrients, 17(23)","doi":"10.3390/nu17233659","pmid":"41373949","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1RAs reduce caloric intake with frequent protein inadequacy and sarcopenia. Deficiencies within 12 months: vitamin D (most common), thiamine/B vitamins, iron, calcium, magnesium, potassium. No formal monitoring protocols exist despite parallel mechanisms to bariatric surgery.","whyItMatters":"With millions on GLP-1 drugs for years, nutritional deficiencies could become a major public health issue. Establishing monitoring protocols now—before widespread deficiency-related complications emerge—is a preventive imperative.","specificNumbers":"","methodology":"Narrative review of PubMed and Embase OVID (August 2025) with three-stage screening. Comparison to bariatric surgery nutritional monitoring guidelines.","limitations":"Narrative review with limited observational data. Causation vs association unclear for some deficiencies. Most data from short-term studies. Optimal monitoring protocols not yet validated for GLP-1 users."},{"rthcId":"RPEP-13593","title":"Blood Pressure-Lowering Effects of SGLT2 Inhibitors and GLP-1 Receptor Agonists.","authors":"Siddiqi, Ahmed Kamal; Khan, Muhammad Shahzeb; Kulkarni, Anandita; Hall, Michael E; Böhm, Michael; Díez, Javier; Butler, Javed","year":2025,"journal":"Current hypertension reports, 27(1), 28","doi":"10.1007/s11906-025-01342-7","pmid":"41324724","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"SGLT2i: SBP -2.5-4.0 mmHg, DBP -1.5-2.0 mmHg, 24h ABPM SBP -3.8 mmHg. GLP-1RA: SBP -1.8-5.1 mmHg, DBP ~0.5 mmHg. Tirzepatide: ~10.6 mmHg SBP in select populations. SGLT2i more consistent; GLP-1RA more variable.","whyItMatters":"Hypertension is the leading modifiable cardiovascular risk factor, and many hypertensive patients have comorbid diabetes. Understanding the BP-lowering effects of these diabetes drugs helps clinicians make treatment decisions that address both conditions simultaneously.","specificNumbers":"","methodology":"Narrative review of clinical trial and meta-analysis data on BP effects of SGLT2i and GLP-1RAs.","limitations":"Review of heterogeneous data. BP effects vary with patient population, dose, and measurement method. Not designed as primary antihypertensives. Tirzepatide data limited."},{"rthcId":"RPEP-13594","title":"Effect of glucagon-like peptide-1 receptor agonists on heart failure outcomes and cardiovascular death across varying cardiovascular-kidney-metabolic comorbidity.","authors":"Siddiqi, Tariq Jamal; Khan, Muhammad Shahzeb; Waqas, Saad Ahmed; Van Spall, Harriette G C; Shapiro, Michael D; Fonarow, Gregg C; Januzzi, James L; Afzal, Aasim M; Pandey, Ambarish; Butler, Javed; Greene, Stephen J","year":2025,"journal":"European journal of heart failure, 27(12), 2844-2854","doi":"10.1002/ejhf.70048","pmid":"40977256","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Composite HFH/CV death: HF HR 0.81, T2DM HR 0.85, obesity HR 0.70, CKD HR 0.79 (NS). CV death reduced in HF (HR 0.88), T2DM (HR 0.85), obesity (HR 0.83). HFrEF exception: HFH HR 1.17 (NS) but CV death HR 0.67 (significant). No increased SAEs (RR 0.94).","whyItMatters":"This provides the most comprehensive evidence yet that GLP-1 drugs benefit the heart across multiple metabolic conditions. The HFrEF signal—possible HF hospitalization increase despite mortality benefit—is a critical nuance for clinical decision-making.","specificNumbers":"","methodology":"Meta-analysis of 15 trials (87,549 patients) from databases through November 2024. Random-effects models for HRs and RRs. Subgroup analyses by disease type and combination.","limitations":"CKD results non-significant. HFrEF signal based on limited data. Post hoc subgroup analyses. Heterogeneity across trials in patient populations and GLP-1 agents. Meta-analysis cannot determine mechanisms."},{"rthcId":"RPEP-13595","title":"Sex differences in the efficacy of GLP-1 receptor agonists: A systematic review and meta-analysis of cardiovascular and renal outcome trials.","authors":"Siddiqui, Hasan Fareed; Ali, Dua; Sajid, Maryam; Qureshi, Shaheer; Siddiqui, Hibah; Hasan, Ali; Ripley, David; Ahmed, Raheel; Waqas, Saad Ahmed","year":2025,"journal":"Diabetes, obesity & metabolism, 27(12), 6847-6856","doi":"10.1111/dom.70123","pmid":"40932012","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Males: MACE -14%, kidney -20%, stroke -21%. Females: MACE -18%, kidney -31%, stroke -25%. No significant sex interactions (all p>0.05). CV death, MI, HHF also similar between sexes.","whyItMatters":"Sex-based differences in drug efficacy are a major concern in cardiovascular medicine. Confirming GLP-1 drugs work equally well in women is important because women have historically been underrepresented in cardiovascular trials.","specificNumbers":"","methodology":"Systematic review and meta-analysis of 11 RCTs (85,273 patients, 43,339 GLP-1RA, 41,934 placebo) reporting sex-stratified outcomes. Random-effects models.","limitations":"Sex-stratified data relies on secondary analyses of trials. Women typically underrepresented. Numerical differences may become significant with larger female samples. Cannot assess dose-response by sex."},{"rthcId":"RPEP-13596","title":"Peptide-targeted nanoparticles for tumor therapy.","authors":"Sidorenko, Valeria; Tobi, Allan; Sugahara, Kazuki N; Teesalu, Tambet","year":2025,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 387, 114195","doi":"10.1016/j.jconrel.2025.114195","pmid":"40925419","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tumor-homing peptides target receptors on tumor vasculature for selective NP delivery. Tumor-penetrating peptides promote extravasation and deep tissue penetration. Peptide targeting exploits molecular differences between healthy and malignant tissue. Review covers accumulation, barrier overcoming, and therapeutic outcomes.","whyItMatters":"Chemotherapy toxicity from non-specific distribution is a major clinical problem. Peptide-targeted delivery could transform cancer treatment by concentrating drugs at tumor sites while dramatically reducing side effects.","specificNumbers":"","methodology":"Narrative review of tumor-homing peptide applications in nanoparticle drug delivery for cancer therapy.","limitations":"Review covers preclinical and early clinical work. In vivo efficacy varies. Manufacturing complexity and cost of peptide-NP conjugates remain challenges. Not all tumors express suitable peptide targets."},{"rthcId":"RPEP-13597","title":"Glucagon-like Peptide-1 receptor agonists versus dipeptidyl-peptidase 4 inhibitors in advanced chronic kidney disease and end stage kidney disease: Real world effectiveness and persistence of therapy.","authors":"Sidra, F N U; Agarwal, Shubham; Lockhart Pastor, Paola; Xie, Donglu; Li, Xilong; Lingvay, Ildiko","year":2025,"journal":"Journal of diabetes and its complications, 39(1), 108925","doi":"10.1016/j.jdiacomp.2024.108925","pmid":"39644537","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1RA vs DPP-4i at 36 months: weight -9.6% vs -2.4% (ETD -7.1 percentage points, p<0.001); HbA1c -1.0% vs +0.2% (ETD -1.2, p=0.04). Treatment duration: GLP-1RA 1036 days, DPP-4i 1109 days.","whyItMatters":"GLP-1 drugs are underused in advanced kidney disease despite guidelines recommending them. This real-world evidence demonstrates they are effective and well-tolerated in this high-risk population, potentially encouraging more appropriate prescribing.","specificNumbers":"","methodology":"Retrospective cohort of 236 patients (149 GLP-1RA, 87 DPP-4i) with T2D and advanced CKD or ESKD. Electronic health records with manual chart review. Outcomes at 36 months.","limitations":"Retrospective, non-randomized. GLP-1RA and DPP-4i groups may differ in unmeasured ways. No cardiovascular or renal outcome data. Single-center. No specific CKD progression data."},{"rthcId":"RPEP-13598","title":"Growth hormone - releasing hormone antagonists induce autophagy in cancer cells.","authors":"Sigdel, Madan; Fakir, Saikat; Sarker, Md Matiur Rahman; Barabutis, Nektarios","year":2025,"journal":"Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society, 82, 101668","doi":"10.1016/j.ghir.2025.101668","pmid":"41075421","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"JV-1-36 elevated ATG-5, ATG-3, ATG-7, ATG-16L1 in GHRH receptor-positive MDA-MB-468 and A549 cells. No effect in GHRH receptor-negative MCF-7 cells. Confirms receptor-dependent autophagy induction.","whyItMatters":"GHRH antagonists are anti-cancer peptides with known anti-inflammatory and anti-oxidative effects. Discovering that autophagy is another mechanism adds to understanding of their multi-modal anti-cancer activity.","specificNumbers":"","methodology":"In vitro treatment of breast (MDA-MB-468, MCF-7) and lung (A549) cancer cell lines with GHRH antagonist JV-1-36. GHRH receptor expression confirmed. Autophagy marker protein levels assessed.","limitations":"In vitro only. Limited to 3 cell lines. Functional significance of autophagy (pro-death vs pro-survival) not determined. No in vivo validation."},{"rthcId":"RPEP-13599","title":"Neuropeptide Y in cancer-biological functions and potential clinical implications.","authors":"Sigorski, Dawid; Sejda, Aleksandra; Abualsaud, Nouran; Krawczyk, Ewa; Izycka-Swieszewska, Ewa; Kitlinska, Joanna","year":2025,"journal":"Cancer metastasis reviews, 44(1), 21","doi":"10.1007/s10555-024-10237-z","pmid":"39760953","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"NPY mediates cancer hallmarks through Y1R/Y2R/Y5R: sustained proliferation, apoptosis resistance, angiogenesis, invasion, and metastasis. Potential applications: prognostic/predictive biomarker, receptor-based imaging, and targeted therapy across multiple cancer types.","whyItMatters":"NPY is one of the most abundant neuropeptides in the body, and its cancer-promoting activities are increasingly recognized. Understanding its role could lead to new diagnostic tools and therapies across multiple cancer types.","specificNumbers":"","methodology":"Comprehensive narrative review of NPY biology in cancer, covering cellular functions, receptor signaling, tumor-type-specific roles, and clinical applications.","limitations":"Narrative review. Evidence varies by cancer type—some have robust data while others have limited studies. Clinical applications are mostly preclinical. NPY system complexity makes therapeutic targeting challenging."},{"rthcId":"RPEP-13600","title":"Skin-Homing Potential of Peripheral Immune Cells From Psoriasis Patients and the Effects of LL-37 on Their Secretion of Chemokines During Psoriasis-Mimicking Stimulation.","authors":"Sigurgrímsdóttir, Hildur; Eysteinsdóttir, Jenna Huld; Kristjánsson, Árni Kjalar; Agnarsson, Bjarni A; Freysdottir, Jona; Lúðvíksson, Björn Rúnar","year":2025,"journal":"Scandinavian journal of immunology, 102(5), e70066","doi":"10.1111/sji.70066","pmid":"41236028","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Psoriatic T cells: increased CCR6, decreased CXCR3-high. Chemokine receptors varied by CLA/CD103 expression. LL-37 modulated chemokine secretion in Th1 and Th17 microenvironments. Th1 and Th17 stimulation produced distinct chemokine secretion clusters by PCA.","whyItMatters":"LL-37 is both a potential psoriasis trigger and autoantigen. Understanding how it modulates immune cell migration to the skin could reveal new therapeutic targets for controlling psoriatic inflammation.","specificNumbers":"","methodology":"Flow cytometry for T cell chemokine receptor and skin-homing marker expression (CLA, CD103, CCR6, CXCR3, CCR4). PBMC stimulation in Th1/Th17 mimicking conditions ± LL-37. Chemokine secretion profiling.","limitations":"In vitro PBMC stimulation may not fully represent skin microenvironment. Observational comparison between psoriasis patients and controls. Specific chemokine effects of LL-37 need functional validation in skin models."},{"rthcId":"RPEP-13601","title":"Stable Gastric Pentadecapeptide BPC 157 as a Therapy and Safety Key: A Special Beneficial Pleiotropic Effect Controlling and Modulating Angiogenesis and the NO-System.","authors":"Sikiric, Predrag; Seiwerth, Sven; Skrtic, Anita; Staresinic, Mario; Strbe, Sanja; Vuksic, Antonia; Sikiric, Suncana; Bekic, Dinko; Soldo, Dragan; Grizelj, Boris; Novosel, Luka; Beketic Oreskovic, Lidija; Oreskovic, Ivana; Stupnisek, Mirjana; Boban Blagaic, Alenka; Dobric, Ivan","year":2025,"journal":"Pharmaceuticals (Basel, Switzerland), 18(6)","doi":"10.3390/ph18060928","pmid":"40573323","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13602","title":"The adverse effects associated with semaglutide use in patients at increased risk of cardiovascular events: a systematic review with meta-analysis and Trial Sequential Analysis.","authors":"Sillassen, Christina Dam Bjerregaard; Petersen, Johanne Juul; Faltermeier, Pascal; Yucel, Delal; Siddiqui, Faiza; Andersen, Rebecca Kjær; Graever, Leonardo; Bjerg, Jonas Leth; Kamp, Caroline Barkholt; Grand, Johannes; Dominguez, Helena; Frølich, Anne; Gæde, Peter; Gluud, Christian; Mathiesen, Ole; Jakobsen, Janus Christian","year":2025,"journal":"BMC medicine, 23(1), 654","doi":"10.1186/s12916-025-04486-0","pmid":"41286875","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Mortality RR 0.85 (95% CI 0.79-0.91, I²=0%). Reduced SAEs and MI. Increased nausea RR 3.00, vomiting RR 4.12, diarrhea RR 1.88. All confirmed by TSA. 50 trials, 54,972 participants.","whyItMatters":"This is the most comprehensive safety analysis of semaglutide to date. While confirming mortality and cardiovascular benefits, it quantifies the GI side effect burden—essential information for prescribing decisions and patient counseling.","specificNumbers":"","methodology":"Systematic review of 6 databases through March 2025. 50 RCTs, 54,972 participants. Meta-analysis with Trial Sequential Analysis. Cochrane Risk of Bias v2. GRADE evidence assessment.","limitations":"Focused on cardiovascular-risk populations. Pooled oral and subcutaneous semaglutide. Non-serious AEs may be underreported. Follow-up durations varied."},{"rthcId":"RPEP-13603","title":"Semaglutide and human reproduction: caution at the intersection of energy balance, ovarian function, and follicular development.","authors":"Sills, E Scott; Harrity, Conor; Chu, Howard I; Wang, Jing-Wen; Yang, Fan; Wood, Samuel H","year":2025,"journal":"Reproductive biology and endocrinology : RB&E, 23(1), 116","doi":"10.1186/s12958-025-01435-7","pmid":"40781307","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"SG affects insulin/AMPK/IGF-1/mTOR/sirtuin pathways that regulate oocyte development, ovarian aging, and embryo implantation. Off-label use could cause starvation/sarcopenia with fertility consequences. No preclinical data exist on ovarian implications of SG.","whyItMatters":"Millions of reproductive-age women are taking semaglutide, often off-label for cosmetic weight loss. The lack of any reproductive safety data is a critical gap, especially for women planning pregnancy or IVF.","specificNumbers":"","methodology":"Narrative review examining GLP-1 signaling pathway intersections with reproductive biology, focusing on energy balance, ovarian function, and follicular development.","limitations":"Review based on pathway analysis, not direct reproductive studies. No clinical or preclinical data specific to SG and fertility. Theoretical concerns may not translate to actual risks."},{"rthcId":"RPEP-13604","title":"Could Glucagon-Like Peptide-1 (GLP-1) receptor antagonists be used to treat obstructive sleep apnoea in children and adolescents with obesity?","authors":"Silva, Dilan; Baur, Louise; Fitzgerald, Dominic A","year":2025,"journal":"Paediatric respiratory reviews","doi":"10.1016/j.prrv.2025.08.001","pmid":"40887408","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Adult evidence: GLP-1RAs reduce body weight up to 15% and significantly decrease OSA severity. Proposed for adolescents with severe obesity + OSA as adjunct to multidisciplinary care. Addresses access inequity in sleep labs and obesity clinics.","whyItMatters":"Pediatric obesity and OSA are growing epidemics with limited treatment options. GLP-1 drugs could fill a critical gap for adolescents who cannot access surgery, tolerate CPAP, or achieve weight loss through lifestyle changes alone.","specificNumbers":"","methodology":"Perspective/opinion article reviewing adult GLP-1RA evidence for OSA and proposing application to adolescents.","limitations":"No direct evidence for GLP-1 drugs in pediatric OSA. Adult evidence extrapolated. Long-term safety in growing adolescents uncertain. Cost and access remain barriers."},{"rthcId":"RPEP-13605","title":"Tirzepatide, a dual agonist of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), positively impacts the altered microbiota of obese, diabetic, ovariectomized mice.","authors":"Silva-Veiga, Flavia Maria; Marinho, Thatiany Souza; de Souza-Mello, Vanessa; Aguila, Marcia Barbosa; Mandarim-de-Lacerda, Carlos Alberto","year":2025,"journal":"Life sciences, 361, 123310","doi":"10.1016/j.lfs.2024.123310","pmid":"39675551","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tirzepatide improved intestinal barrier (increased Cldn12, Ocln, JamA, decreased Muc2), reduced inflammation (decreased macrophage activation), reversed dysbiosis (decreased Firmicutes/Bacteroidetes ratio, increased Bifidobacterium, Akkermansia, Bacteroides, Prevotella). Treatment: 10 nmol/kg for 4 weeks.","whyItMatters":"Gut health is increasingly recognized as central to metabolic disease. Showing that tirzepatide repairs the intestinal barrier and corrects dysbiosis suggests a new mechanism by which GLP-1/GIP drugs improve metabolic health—beyond appetite and blood sugar control.","specificNumbers":"","methodology":"Female C57BL/6 mice model: ovariectomized + diet-induced obesity + diabetes. 8 groups (n=30/group). Tirzepatide 10 nmol/kg for 4 weeks. Ileum structure/molecular analysis, cecal fecal microbiota 16S rRNA sequencing.","limitations":"Mouse model with extreme conditions (ovariectomy + obesity + diabetes). 4-week treatment duration. Mechanisms of gut improvement not fully delineated. Human microbiome may respond differently."},{"rthcId":"RPEP-13606","title":"GLP-1 receptor agonists and the risk for cancer: A meta-analysis of randomized controlled trials.","authors":"Silverii, Giovanni Antonio; Marinelli, Christian; Bettarini, Costanza; Del Vescovo, Gloria Giovanna; Monami, Matteo; Mannucci, Edoardo","year":2025,"journal":"Diabetes, obesity & metabolism, 27(8), 4454-4468","doi":"10.1111/dom.16489","pmid":"40437949","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Overall cancer: MH-OR 1.05 (NS). Thyroid cancer: OR 1.55 (1.05-2.27, significant, worse in longer trials). Colorectal cancer: OR 1.27 (1.03-1.57, significant in shorter trials only). Uterine cancer in obesity: OR 0.24 (0.06-0.94, significant). No other cancers affected.","whyItMatters":"With millions taking GLP-1 drugs, cancer safety is critical. This analysis reassures about overall cancer risk but identifies thyroid cancer as a genuine concern requiring ongoing monitoring and uterine cancer reduction as an important benefit.","specificNumbers":"","methodology":"Meta-analysis of 50 RCTs comparing GLP-1RAs to any comparators for diabetes/obesity, lasting ≥52 weeks. Endpoints: overall and site-specific cancer incidence.","limitations":"Cancer as a secondary outcome in most trials (not powered for cancer detection). Short follow-up for cancer development. Thyroid cancer screening practices may vary. Colorectal increase may reflect diagnostic bias."},{"rthcId":"RPEP-13607","title":"No additional benefit with detoxification strategies: A real world experience in 200 patients with chronic migraine and either simple or complex MOH treated with CGRP monoclonal antibodies.","authors":"Silvestro, Marcello; Orologio, Ilaria; Sozio, Pasquale; Dortucci, Valentina; Trojsi, Francesca; Siciliano, Mattia; Tedeschi, Gioacchino; Tessitore, Alessandro; Russo, Antonio","year":2025,"journal":"Cephalalgia : an international journal of headache, 45(6), 3331024251329808","doi":"10.1177/03331024251329808","pmid":"40457764","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Both simple and complex MOH patients improved significantly on CGRP-mAbs at months 1, 3, and 6. Adding detoxification provided no additional benefit (p>0.05 for all comparisons). Reduced: headache frequency, intensity, duration, acute medication days. 200 patients total.","whyItMatters":"Analgesic detoxification is unpleasant and a barrier to MOH treatment. Showing that CGRP-mAbs work without it could encourage more patients to seek treatment and simplify clinical management of this common and disabling condition.","specificNumbers":"","methodology":"Six-month observational study of 200 chronic migraine/MOH patients on subcutaneous CGRP-mAbs. Stratified by MOH complexity and detoxification strategy. Outcomes at 1, 3, and 6 months.","limitations":"Observational, non-randomized. Selection bias possible. Single center. Six-month follow-up may not capture all relapse patterns. CGRP-mAb type not specified."},{"rthcId":"RPEP-13608","title":"Obesity and heart failure-the role of GLP-1 receptor agonists.","authors":"Simonis, Gregor; Schatz, Ulrike","year":2025,"journal":"Herz, 50(4), 246-252","doi":"10.1007/s00059-025-05312-2","pmid":"40172656","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1RAs and tirzepatide improve symptoms and outcomes in obesity-driven HFpEF beyond standard guideline-recommended therapy. Obesity drives HFpEF through multiple pathophysiological mechanisms that GLP-1 drugs can target.","whyItMatters":"HFpEF affects half of heart failure patients and is the most common form in obese individuals. Standard treatments are often inadequate, making GLP-1 drugs a much-needed additional therapy.","specificNumbers":"","methodology":"Narrative review of clinical trial data on GLP-1RAs and tirzepatide in obesity-driven HFpEF.","limitations":"Short abstract with limited detail. Review format. Long-term HFpEF outcome data still needed."},{"rthcId":"RPEP-13609","title":"Aging and Thymosin Alpha-1.","authors":"Simonova, Maria A; Ivanov, Igor; Shoshina, Natalia S; Komyakova, Alina M; Makarov, Dmitry A; Baranovskii, Denis S; Klabukov, Ilya D; Telepenina, Kristina P; Atiakshin, Dmitrii A; Shegay, Peter V; Kaprin, Andrey D; Stepanenko, Vasiliy N","year":2025,"journal":"International journal of molecular sciences, 26(23)","doi":"10.3390/ijms262311470","pmid":"41373628","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tα1 stimulates T-cell differentiation, enhances thymic output, modulates DCs and macrophages, has anti-inflammatory and antioxidant properties. Improves vaccine response in elderly. Refnot (TNFα-Tα1 fusion) combines immunomodulation with antitumor activity at reduced toxicity.","whyItMatters":"Aging-related immune decline (immunosenescence) is a major driver of disease in the elderly. Tα1 offers a peptide-based approach to reversing this decline, with proven ability to improve vaccine responses—critical for protecting aging populations.","specificNumbers":"","methodology":"Narrative review of preclinical and clinical evidence for Tα1 in aging and immunosenescence.","limitations":"Review format. Long-term efficacy and safety data in geriatric populations limited. Refnot data primarily from oncology settings. Mechanism of anti-aging effect needs clarification."},{"rthcId":"RPEP-13610","title":"Use of semaglutide and risk of non-arteritic anterior ischemic optic neuropathy: A Danish-Norwegian cohort study.","authors":"Simonsen, Emma; Lund, Lars Christian; Ernst, Martin Thomsen; Hjellvik, Vidar; Hegedüs, Laszlo; Hamann, Steffen; Jørstad, Øystein Kalsnes; Gulseth, Hanne Løvdal; Karlstad, Øystein; Pottegård, Anton","year":2025,"journal":"Diabetes, obesity & metabolism, 27(6), 3094-3103","doi":"10.1111/dom.16316","pmid":"40098249","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Pooled HR 2.81 (95% CI 1.67-4.75). Denmark HR 2.17 (1.20-3.92), Norway HR 7.25 (2.34-22.4). IRD +1.41/10,000 person-years. Per-protocol HR 6.35 (2.88-14.0). 32 NAION events total. Consistent across sensitivity analyses.","whyItMatters":"NAION causes sudden, irreversible vision loss. This is the largest and most rigorous study confirming the association with semaglutide, providing critical safety information for millions of users.","specificNumbers":"","methodology":"Population-based cohort study using national health registries in Denmark (2018-2024) and Norway (2018-2022). Active comparator (SGLT2i). Fixed-effects meta-analysis pooling. Self-controlled supplementary analysis.","limitations":"Observational study—cannot prove causation. Active comparator design (vs SGLT2i) may inflate or deflate relative risk. NAION events rare (32 total). Norwegian estimates less precise. Potential for residual confounding."},{"rthcId":"RPEP-13611","title":"Neuropeptide Y as a multifaceted modulator of neuroplasticity, Neuroinflammation, and HPA axis dysregulation: Perceptions into treatment-resistant depression.","authors":"Singanwad, Priyanka; Tatode, Amol; Qutub, Mohammad; Taksande, Brijesh; Umekar, Milind; Trivedi, Rashmi; Premchandani, Tanvi","year":2025,"journal":"Neuropeptides, 112, 102538","doi":"10.1016/j.npep.2025.102538","pmid":"40663867","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Decreased CSF NPY in TRD patients. Reduced NPY receptor expression in stress-related brain regions. Animal models: NPY dysregulation in chronic stress with altered hippocampal signaling and HPA axis. Therapeutic targets: intranasal NPY, receptor-selective modulators.","whyItMatters":"TRD affects about one-third of depressed patients and has few effective treatments. NPY represents a biologically grounded target distinct from serotonin/norepinephrine pathways targeted by conventional antidepressants.","specificNumbers":"","methodology":"Narrative review synthesizing preclinical (animal stress models) and clinical (CSF biomarker, receptor expression) evidence for NPY in TRD.","limitations":"Review format. Clinical NPY data limited. Intranasal NPY delivery still experimental. Causation vs association for NPY decreases in TRD unclear."},{"rthcId":"RPEP-13612","title":"Comparative efficacy and safety of semaglutide 2.4 mg and tirzepatide 5-15 mg in obesity with or without type 2 diabetes: A systematic review of Phase 3 clinical trials.","authors":"Singh, Akriti; Singh, Awadhesh Kumar; Singh, Ritu; Misra, Anoop","year":2025,"journal":"Diabetes & metabolic syndrome, 19(3), 103212","doi":"10.1016/j.dsx.2025.103212","pmid":"40086043","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tirzepatide vs semaglutide (ITT): 4% (10mg) and 5.4% (15mg) additional weight loss without T2D; additional -0.4% HbA1c with T2D; fewer GI side effects with tirzepatide.","whyItMatters":"Head-to-head data is limited. This indirect comparison helps clinicians choose between the two most important obesity drugs, showing tirzepatide's advantages in both efficacy and tolerability.","specificNumbers":"","methodology":"Systematic review of PubMed through December 2024. Indirect treatment comparison of matched STEP (semaglutide) and SURMOUNT (tirzepatide) phase 3 RCTs.","limitations":"Indirect comparison—not a head-to-head trial. Some differences between trial populations may exist. ITT analysis may underestimate on-treatment differences."},{"rthcId":"RPEP-13613","title":"The PANEN nomogram: clinical decision support for patients with metastatic pancreatic neuroendocrine neoplasm referred for peptide receptor radionuclide therapy.","authors":"Singh, Aviral; Sanduleanu, Sebastian; Kulkarni, Harshad R; Langbein, Thomas; Lambin, Philippe; Baum, Richard P","year":2025,"journal":"Frontiers in endocrinology, 16, 1514792","doi":"10.3389/fendo.2025.1514792","pmid":"40630096","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"17 independent OS predictors identified. Top predictors: time to PRRT, alkaline phosphatase, KPS, hepatomegaly, weight loss, FDG-PET positivity, Ki-67 grade. C-index: 0.86 (development), 0.82 (test). Median follow-up: 2045 days.","whyItMatters":"PRRT is expensive and involves radiation. Having a validated prediction tool helps clinicians identify which patients are most likely to benefit, optimizing treatment selection and enabling better-informed patient counseling.","specificNumbers":"","methodology":"Retrospective analysis of 447 pancreatic NEN patients treated with PRRT. Random survival forests (RSF) modeling. 80/20 train/test split. Internal validation. Nomogram construction.","limitations":"Single-center retrospective data. Internal validation only—external validation needed. RSF models can be less interpretable than traditional regression. Not all variables may be available at all centers."},{"rthcId":"RPEP-13614","title":"Tirzepatide: A Breakthrough Therapy for Obstructive Sleep Apnea and Metabolic Dysfunction.","authors":"Singh, Gursimran; Jaswal, Taresh; Kosey, Sourabh; Kumar, Ranjeet; Kaur, Amandeep","year":2025,"journal":"Current hypertension reviews","doi":"10.2174/0115734021398680251001102514","pmid":"41140212","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tirzepatide addresses OSA through: reduced airway fat deposition, improved insulin sensitivity, decreased inflammation, weight loss. Clinical studies show AHI improvement and better oxygenation.","whyItMatters":"OSA affects an estimated 1 billion people globally and is primarily driven by obesity. A drug that simultaneously addresses obesity, metabolism, and airway fat could transform OSA treatment beyond CPAP and surgery.","specificNumbers":"","methodology":"Narrative review of tirzepatide mechanisms relevant to OSA, with examination of clinical trial evidence.","limitations":"Review format. Clinical OSA data still emerging. Long-term effects on OSA outcomes unknown. May not help non-obese OSA patients."},{"rthcId":"RPEP-13615","title":"Association between glucagon-like peptide-1 agonists and risk of diabetic retinopathy: a disproportionality analysis using FDA adverse event reporting system data.","authors":"Singh, Harmanjit; Natt, Navreet Kaur; Nim, Dwividendra Kumar","year":2025,"journal":"Expert review of endocrinology & metabolism, 20(2), 147-152","doi":"10.1080/17446651.2025.2459720","pmid":"39873334","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide: PRR 19.43, ROR 19.48, Chi² 1078. Dulaglutide: PRR 9.01, ROR 9.02, Chi² 478. Tirzepatide and liraglutide: weaker but significant. Lixisenatide: no significant association.","whyItMatters":"With millions using GLP-1 drugs, the diabetic retinopathy signal—especially for semaglutide—warrants clinical attention. While causation is unclear, the strong disproportionality suggests either a true risk or significant reporting bias that needs investigation.","specificNumbers":"","methodology":"Disproportionality analysis of FDA FAERS database Q4/2003-Q2/2024 via OpenVigil 2.1. Calculated PRR, ROR with 95% CI. Evans' criteria for significance.","limitations":"FAERS data is spontaneous reports—subject to reporting bias, confounding, and cannot establish causation or incidence. Semaglutide's high reporting may reflect greater market share and awareness. No denominator (number of users) available."},{"rthcId":"RPEP-13616","title":"Calcitonin gene-related peptide (CGRP): A potential therapeutic target against sepsis and sepsis-associated multiple organ failure.","authors":"Singh, Harshita; Naik, Manoj; Suri, Manisha; Hanifa, Mohd; Jaggi, Amteshwar Singh; Bali, Anjana","year":2025,"journal":"Biochemical pharmacology, 242(Pt 3), 117206","doi":"10.1016/j.bcp.2025.117206","pmid":"40754169","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CGRP reduces inflammatory cytokines, inhibits oxidative stress, and decreases organ inflammation in sepsis. RAMP1 and TRPV1 knockout mice showed worse sepsis outcomes. CGRP modulates specific signaling pathways for organ-specific protection.","whyItMatters":"Sepsis kills millions annually with limited treatment options. CGRP agonism could provide a novel therapeutic approach targeting both inflammation and organ protection simultaneously.","specificNumbers":"","methodology":"First comprehensive review of in vitro and in vivo evidence for CGRP in sepsis-associated organ dysfunction.","limitations":"Review of preclinical evidence. No clinical trials of CGRP agonists for sepsis. Timing and dosing of CGRP in sepsis are undefined. CGRP's vasodilatory effects could worsen septic shock if not carefully managed."},{"rthcId":"RPEP-13617","title":"Beyond Glycemic Control: Glucagon-Like Peptide-1 Receptor Agonists as Potential Modifiers of Aortic Disease.","authors":"Singh, Kanwardeep; Frishman, William H","year":2025,"journal":"Cardiology in review","doi":"10.1097/CRD.0000000000001045","pmid":"40963159","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1RAs inhibit IL-1β, TNF-α, MMPs; preserve elastin; promote M2 macrophages; slow aneurysm growth in animals. Clinical: fewer limb events, improved walking in PAD. No evidence for aortic regurgitation.","whyItMatters":"Aortic aneurysms and peripheral artery disease have few effective medical therapies. If GLP-1 drugs can modify aortic disease, millions of at-risk patients could benefit from drugs already in widespread use.","specificNumbers":"","methodology":"Narrative review of animal studies, population data, and cardiovascular outcome trials through May 2025.","limitations":"Mostly preclinical evidence. Aortic-specific clinical trials are lacking. Observational data subject to confounding. No evidence for valve disease."},{"rthcId":"RPEP-13618","title":"Intranasal amyloid model of Alzheimer's disease - potential opportunities and challenges.","authors":"Singh, Rakesh Kumar","year":2025,"journal":"Pharmacological reports : PR, 77(2), 425-433","doi":"10.1007/s43440-024-00692-4","pmid":"39775701","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Intranasal Aβ1-42 induces AD-like pathology non-transgenically. Advantages: more accurate disease progression, no genetic manipulation. Challenges: dose standardization, timeline optimization. Potential to improve preclinical drug testing.","whyItMatters":"AD drug development has an extremely high failure rate partly due to inadequate animal models. A non-transgenic model that better replicates human disease could improve the predictive value of preclinical studies and accelerate therapeutic discovery.","specificNumbers":"","methodology":"Review of preclinical studies using intranasal amyloid-beta animal models of AD.","limitations":"Review of developing model—standardization incomplete. Limited validation across laboratories. Does not replicate all AD features (e.g., tau pathology). Duration needed for full pathology development unclear."},{"rthcId":"RPEP-13619","title":"Euglycemic Ketoacidosis in a Non-diabetic Patient After Tirzepatide Use: A Cautionary Tale.","authors":"Singh, Renisha","year":2025,"journal":"Cureus, 17(4), e83187","doi":"10.7759/cureus.83187","pmid":"40443633","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Non-diabetic woman, BMI 30.4, online prescription tirzepatide. Self-titrated to 5 mg over 6 weeks. Lost 16 lbs. Developed EKA: pH 7.2, bicarb 17, elevated ketones, normal glucose. Recovered with fluids.","whyItMatters":"This is a non-diabetic EKA case—expanding the known risk population beyond diabetics. The online prescription pathway highlights the growing danger of unsupervised GLP-1 drug access.","specificNumbers":"","methodology":"Single case report with clinical presentation and management.","limitations":"Single case. Causation assumed but other factors may have contributed. Non-diabetic EKA is very rare. Online prescribing context may not be representative."},{"rthcId":"RPEP-13620","title":"Obesity as a Chronic Disease: A Narrative Review of Evolving Definitions, Management Strategies, and Cardiometabolic Prioritization.","authors":"Singh, Vidhi; Sun, Jia; Cheng, Susan; Kwan, Alan C; Velazquez, Amanda","year":2025,"journal":"Advances in therapy, 42(11), 5341-5364","doi":"10.1007/s12325-025-03352-y","pmid":"40911213","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BMI inadequate for individual obesity assessment. GLP-1 drugs (semaglutide, tirzepatide) provide weight loss + cardiovascular, renal, liver benefits. <25% of obese individuals receive evidence-based treatment. Need for upstream, cardiometabolic-focused approach.","whyItMatters":"The gap between effective treatments (especially GLP-1 drugs) and actual treatment delivery is enormous. Reframing obesity as a chronic disease requiring proactive medical management could improve access to transformative therapies.","specificNumbers":"","methodology":"Narrative review of evolving obesity definitions, management strategies, and cardiometabolic prioritization.","limitations":"Narrative review. US-centric healthcare perspective. Treatment access barriers (cost, insurance) not fully addressed."},{"rthcId":"RPEP-13621","title":"Unmasking Semaglutide-Induced Gastroparesis: The Dangers of Rapid Dose Escalation in a Diabetic Patient.","authors":"Singhal, Rohan; Sachdeva, Dheerja; Wortman Ii, Kevin; Lall, Rekha","year":2025,"journal":"Cureus, 17(9), e91679","doi":"10.7759/cureus.91679","pmid":"41054677","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Gastroparesis after semaglutide 2 mg resumed without titration. Complications: AKI from dehydration + left-sided colitis. Treatment: metoclopramide + semaglutide cessation → resolution.","whyItMatters":"Many patients restart GLP-1 drugs at prior doses after breaks, not realizing the body loses tolerance. This case demonstrates that dose re-titration is essential to prevent serious GI complications.","specificNumbers":"","methodology":"Single case report.","limitations":"Single case. Gastroparesis may have pre-existed. Other contributing factors possible. Cannot establish incidence."},{"rthcId":"RPEP-13622","title":"Efficacy and Safety of GLP-1 Receptor Agonists, Dual Agonists, and Retatrutide for Weight Loss in Adults With Overweight or Obesity: A Bayesian NMA.","authors":"Sinha, Binayak; Ghosal, Samit","year":2025,"journal":"Obesity (Silver Spring, Md.), 33(11), 2046-2054","doi":"10.1002/oby.24360","pmid":"40685589","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Mean weight loss: retatrutide ~11 kg, dual agonists ~11 kg, GLP-1RAs ~9 kg. ≥15% weight loss OR: retatrutide 54.6, dual 16.4, GLP-1RA 9.0. T2DM reduced loss by 4-5 kg. Retatrutide: highest AE risk. Female/high-BMI: better outcomes.","whyItMatters":"This is the first comprehensive NMA comparing all incretin-based weight loss drug classes. It establishes the efficacy hierarchy and identifies which patients respond best to each class.","specificNumbers":"","methodology":"Systematic review and Bayesian NMA of 19 RCTs (29,506 adults, BMI ≥25). Agents: liraglutide, semaglutide, survodutide, tirzepatide, retatrutide vs placebo. Outcomes at ≥36 weeks. Subgroup analyses by diabetes, sex, age, BMI.","limitations":"Bayesian NMA has inherent assumptions. Retatrutide data limited (fewer trials). Head-to-head comparisons sparse. Different trial durations and populations."},{"rthcId":"RPEP-13623","title":"The effects of glucagon-like peptide-1 receptor agonists (GLP1-RAs) on alcohol-related outcomes: a systematic review and meta-analysis.","authors":"Sinha, Binayak; Ghosal, Samit","year":2025,"journal":"Addiction science & clinical practice, 21(1), 8","doi":"10.1186/s13722-025-00637-z","pmid":"41350683","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Observational: HR 0.64 for alcohol events (p<0.001); AUD HR 0.66; SUD HR 0.66; intoxication HR 0.50. RCTs (n=430): consumption SMD -0.24 (NS); drinks/day SMD -0.23 (NS); craving SMD -0.14 (NS). Semaglutide craving reduction p=0.024.","whyItMatters":"Alcohol use disorder has few effective medications. The strong observational signal combined with semaglutide's significant craving reduction provides compelling rationale for larger dedicated trials.","specificNumbers":"","methodology":"Systematic review and meta-analysis per PRISMA. 3 RCTs (430 patients) + 6 observational (2,740,207 patients). Random-effects with REML and Hartung-Knapp adjustment.","limitations":"RCTs underpowered (n=430). Observational data subject to confounding. Different outcome definitions across studies. Alcohol was rarely the primary endpoint."},{"rthcId":"RPEP-13624","title":"Machine Learning Uncovers Novel Predictors of Peptide Receptor Radionuclide Therapy Eligibility in Neuroendocrine Neoplasms.","authors":"Sipka, Gábor; Farkas, István; Bakos, Annamária; Maráz, Anikó; Mikó, Zsófia Sára; Czékus, Tamás; Bukva, Mátyás; Urbán, Szabolcs; Pávics, László; Besenyi, Zsuzsanna","year":2025,"journal":"Cancers, 17(17)","doi":"10.3390/cancers17172935","pmid":"40941032","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Models predicted SSTR expression with 70-83% accuracy using clinical parameters. Key predictors: tumor origin, oncological treatments, CK7. Associations: age, grade, disease extent, CEA, CA19-9, AFP. 65 patients, 392 lesions evaluated.","whyItMatters":"PRRT requires expensive somatostatin receptor imaging for patient selection. Predictive models using routine clinical data could pre-screen patients, reducing costs and accelerating treatment decisions.","specificNumbers":"","methodology":"Retrospective study of 65 patients with metastatic NENs. SPECT/CT imaging with [99mTc]Tc-EDDA/HYNIC-TOC. Mathematical models built from histological, oncological, immunohistochemical, and laboratory parameters.","limitations":"Retrospective single-center. Moderate sample size. Prediction accuracy (70-83%) not perfect. External validation needed. Used SPECT/CT rather than PET/CT."},{"rthcId":"RPEP-13625","title":"Incretin Mimetics as Potential Therapeutics for Concussion and Traumatic Brain Injury: A Narrative Review.","authors":"Sipos, Samuel; Jerkic, Mirjana; Rotstein, Ori D; Schweizer, Tom A","year":2025,"journal":"International journal of molecular sciences, 27(1)","doi":"10.3390/ijms27010045","pmid":"41515925","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Incretins reduce neuroinflammation, protect BBB, and promote neuronal survival in TBI models. 70 million annual TBI cases (81% concussions). Already safe in diabetes patients. Ideal for rapid clinical trial evaluation.","whyItMatters":"TBI has essentially no disease-modifying treatments. Repurposing already-approved GLP-1 drugs could provide a neuroprotective therapy much faster than developing new drugs from scratch.","specificNumbers":"","methodology":"Narrative review of cellular and animal TBI studies plus limited clinical evidence for incretin-based neuroprotection.","limitations":"Mostly preclinical evidence. Limited clinical TBI data. Optimal dosing, timing post-injury, and patient selection unknown. BBB penetration of some incretins may be limited."},{"rthcId":"RPEP-13626","title":"Substance P Augments Chemokine Production by Staphylococcus aureus Infected Murine Osteoclasts.","authors":"Sipprell, Sophie E; Krueger, Quinton A; Mills, Erin L; Marriott, Ian; Johnson, M Brittany","year":2025,"journal":"Inflammation, 48(5), 3506-3518","doi":"10.1007/s10753-025-02280-x","pmid":"40056352","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Substance P increases chemokine release (not gene expression) from S. aureus-infected osteoclasts but not osteoblasts. NK-1R inhibition reduced disease severity in mouse osteomyelitis. Reduced leukocyte-attracting chemokines and osteoclast/neutrophil activity in vivo.","whyItMatters":"Staphylococcal osteomyelitis is difficult to treat and causes progressive bone destruction. Identifying substance P as a driver of this destruction—and showing NK-1R blockade helps—opens a new therapeutic avenue for a challenging infection.","specificNumbers":"","methodology":"In vivo mouse staphylococcal osteomyelitis model with NK-1R inhibition. In vitro bone marrow-derived osteoclast cultures with S. aureus infection ± substance P. Gene expression and protein release assays.","limitations":"Mouse model may not fully represent human osteomyelitis. Only substance P tested—other neuropeptides may be involved. NK-1R antagonists are available (aprepitant) but not tested for osteomyelitis clinically."},{"rthcId":"RPEP-13627","title":"Can GLP-1 agonists be used safely in inflammatory bowel disease? A meta-analysis.","authors":"Siranart, Noppachai; Nakaphan, Pannathorn; Pajareya, Patavee; Laohasurayotin, Khamik","year":2025,"journal":"Journal of Crohn's & colitis, 19(12)","doi":"10.1093/ecco-jcc/jjaf193","pmid":"41212197","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"No increased risk: corticosteroids OR 0.93, treatment escalation OR 0.70, surgery OR 0.32. Weight loss: -7.33 kg (I²=0%), -6.67% body weight (I²=0%), BMI -2.48 (I²=0%). Flare incidence: 14%. 10,362 patients across 10 studies.","whyItMatters":"Clinicians have been hesitant to prescribe GLP-1 drugs to IBD patients due to overlapping GI symptoms. This is the most comprehensive safety analysis to date, providing reassurance that these drugs can be used safely.","specificNumbers":"","methodology":"Systematic review through June 2025. 10 observational studies, 10,362 IBD patients (3,479 GLP-1RA, 6,883 controls). Pooled ORs and mean changes.","limitations":"All observational studies. Heterogeneity high for surgery outcome (I²=92.5%). Most studies short-term. Cannot exclude long-term risks. Selection bias possible."},{"rthcId":"RPEP-13628","title":"Efficacy and safety of semaglutide versus placebo for people with schizophrenia on clozapine with obesity (COaST): a phase 2, multi-centre, participant and investigator- blinded, randomised controlled trial in Australia.","authors":"Siskind, Dan; Baker, Andrea; Arnautovska, Urska; Warren, Nicola; Russell, Anthony; DeMonte, Veronica; Halstead, Sean; Iyer, Ravi; Korman, Nicole; McKeon, Gemma; Medland, Sarah; Parker, Stephen; Stedman, Terry; Trott, Mike","year":2025,"journal":"The lancet. Psychiatry, 12(7), 493-503","doi":"10.1016/S2215-0366(25)00129-4","pmid":"40506208","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide: -13.88% weight vs placebo -0.42% (difference -13.46%, p<0.0001). No change in clozapine/norclozapine levels. No change in PANSS psychosis scores. No treatment-related SAEs. Low constipation rates. 31 patients (15 sema, 16 placebo).","whyItMatters":"Clozapine users have the worst metabolic profiles of all psychiatric patients, contributing to 16-20 year shorter life expectancy. This trial shows semaglutide can produce dramatic weight loss in this population without psychiatric risks—a potential life-saving intervention.","specificNumbers":"","methodology":"Phase 2 multi-site Australian RCT (COaST). Double-blind, placebo-controlled. 31 adults with schizophrenia on clozapine ≥18 weeks, BMI ≥26. Semaglutide titrated to 2.0 mg SC weekly for 36 weeks.","limitations":"Very small sample (31 vs planned 80) due to supply issues. Phase 2 trial. Short follow-up. Predominantly White sample. Single-country. Recruitment challenges suggest real-world feasibility concerns."},{"rthcId":"RPEP-13629","title":"Comparative effectiveness of GLP-1 receptor agonists on cardiovascular outcomes among adults with type 2 diabetes and moderate cardiovascular risk: emulation of a target trial.","authors":"Sklepinski, Stacey M; Deng, Yihong; Swarna, Kavya Sindu; Herrin, Jeph; Polley, Eric C; Neumiller, Joshua J; Galindo, Rodolfo J; Umpierrez, Guillermo E; Ross, Joseph S; Borah, Bijan J; Maron, Bradley A; Mickelson, Mindy M; McCoy, Rozalina G","year":2025,"journal":"Diabetes research and clinical practice, 229, 112910","doi":"10.1016/j.diabres.2025.112910","pmid":"40983112","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"vs Dulaglutide: Semaglutide MACE HR 0.85, mortality HR 0.81, stroke HR 0.82, revascularization HR 0.93. Liraglutide MACE HR 0.84, mortality HR 0.79. Exenatide: no significant differences. 81,854 patients at moderate CV risk.","whyItMatters":"Most GLP-1 CV outcome data comes from high-risk patients. This study shows semaglutide and liraglutide provide CV protection even in moderate-risk T2D patients, potentially expanding the population that should receive these drugs.","specificNumbers":"","methodology":"Target trial emulation using claims data (2014-2021). 81,854 patients. Propensity score IPTW Cox models. Compared dulaglutide, exenatide, liraglutide, semaglutide.","limitations":"Observational target trial emulation—not a randomized trial. Residual confounding possible. Claims data lacks clinical detail. US-centric."},{"rthcId":"RPEP-13630","title":"Efficacy of Anti-Obesity Medications in Adult and Older Adult Veteran Populations.","authors":"Smit, Haley; Hayen, Krista; Schartz, Kathryn; Metzger, Justin; Perry, Meghan","year":2025,"journal":"Federal practitioner : for the health care professionals of the VA, DoD, and PHS, 42(2), 90-94","doi":"10.12788/fp.0553","pmid":"40529839","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"No significant weight loss difference at 6 months (p=0.08) or 12 months (p=0.26) between age groups. Similar HbA1c (p=0.73), LDL (p=0.95), and BP changes. Fewer AEs in older adults (39% vs 61%). Lower AE-related discontinuation in older adults (0% vs 6%).","whyItMatters":"Clinicians often hesitate to prescribe weight loss medications to older adults due to safety concerns. This study provides reassurance that they are effective and possibly better tolerated in this population.","specificNumbers":"","methodology":"Retrospective cohort at VA Sioux Falls (Jan 2021-June 2023). 144 veterans (116 adults <65, 28 older adults ≥65) prescribed anti-obesity medications.","limitations":"Small sample, especially older adult group (n=28). Single VA site. Retrospective. Predominantly male veteran population. Multiple AOMs grouped together."},{"rthcId":"RPEP-13631","title":"Lower risk of cardiovascular events in patients initiated on semaglutide 2.4 mg in the real-world: Results from the SCORE study (Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity in the Real World).","authors":"Smolderen, Kim G; Mena-Hurtado, Carlos; Zhao, Zhenxiang; Michalak, Wojciech; Faurby, Mads; Smolarz, B Gabriel; Kosiborod, Mikhail N; Song, Jinlin; Chen, Yan; Boland, Joanna; Nanna, Michael G","year":2025,"journal":"Diabetes, obesity & metabolism, 27(11), 6691-6704","doi":"10.1111/dom.70080","pmid":"40926360","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"rMACE-3 HR 0.43 (p<0.001); rMACE-5 HR 0.55 (p<0.001); MACE-3 HR 0.58 (p<0.01); MACE-5 HR 0.65 (p<0.001). Reduced all-cause mortality, CV mortality, HF hospitalization, incident T2DM, and kidney events. 9,321 vs 18,642 matched.","whyItMatters":"This is the first real-world confirmation of the SELECT trial findings, showing semaglutide 2.4 mg provides substantial cardiovascular protection in non-diabetic obese patients with existing heart disease.","specificNumbers":"","methodology":"Propensity-score matched cohort study from US database (2016-2023). 1:2 matching. 9,321 semaglutide 2.4 mg users. Mean follow-up 200 days. NCT06874751.","limitations":"Observational—larger effect sizes than SELECT trial may reflect residual confounding. Short mean follow-up (200 days). US-only database. Interim analysis."},{"rthcId":"RPEP-13632","title":"Effectiveness of Semaglutide and Tirzepatide in Overweight and Obese Adults with Type 1 Diabetes.","authors":"Snell-Bergeon, Janet K; Kaur, Gurleen; Renner, Drew; Akturk, Halis K; Beatson, Christie; Garg, Satish K","year":2025,"journal":"Diabetes technology & therapeutics, 27(1), 1-9","doi":"10.1089/dia.2024.0328","pmid":"39745353","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide: -19.2 lbs (-9.1%), HbA1c -0.54% (p=0.0001). Tirzepatide: -49.4 lbs (-21.4%), HbA1c -0.68%. Controls: no significant changes. 100 T1D patients over 1 year.","whyItMatters":"Obesity in T1D is growing due to intensive insulin therapy and has no approved drug treatment. These off-label results—especially tirzepatide's 21.4% weight loss—are striking and justify formal clinical trials.","specificNumbers":"","methodology":"Retrospective chart review of 100 T1D adults (50 semaglutide, 50 tirzepatide) plus 50 frequency-matched controls at a specialty diabetes clinic over 1 year.","limitations":"Retrospective, non-randomized. Off-label use. Small sample. Safety concerns (DKA risk in T1D) not comprehensively assessed. Selection bias likely."},{"rthcId":"RPEP-13633","title":"The Impact of Liraglutide on Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease.","authors":"So, Jae Eun; Jeong, Jaehong; Hong, Jung Pyo; Kim, Dong Yun; Lee, Jae Seung; Kim, Mi Na; Kim, Beom Kyung; Park, Jun Yong; Kim, Do Young; Lee, Hye Won; Kim, Seung Up","year":2025,"journal":"Journal of gastroenterology and hepatology, 40(12), 2976-2986","doi":"10.1111/jgh.70134","pmid":"41194677","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CAP (liver fat): -26.0 dB/m at 2 months (p significant). Liver stiffness: no significant change. BMI: 30.9→28.9 (p<0.001). HOMA-IR improved. MASLD criteria prevalence declined. 197 patients, 6-month follow-up.","whyItMatters":"Distinguishing between fat reduction and fibrosis improvement is critical—while liraglutide reduces liver fat, the lack of stiffness improvement suggests it may not reverse established fibrosis. This has implications for treatment expectations.","specificNumbers":"","methodology":"Retrospective cohort of 197 MASLD patients (2020-2023). VCTE (FibroScan) at baseline, 2 and 6 months. Metabolic parameter tracking.","limitations":"Retrospective. Significant dropout (197→142 at 6 months). VCTE has limitations for fibrosis assessment. No control group. Short follow-up for fibrosis changes."},{"rthcId":"RPEP-13634","title":"The Role of Glucagon-Like Peptide-1 Receptor Agonists in Post ST-Segment Elevation Myocardial Infarction Care: A Scoping Review.","authors":"Soares, Leticia Alves; Paniagua, Cynthia; Nguyen, Julie; Kojic, Ajla; Sanfrey, Elena Rose; Reyome, Madison Emilee; Aguayo, Liliana; Sattler, Elisabeth Lilian Pia","year":2025,"journal":"Current epidemiology reports, 12(1), 22","doi":"10.1007/s40471-025-00375-5","pmid":"41230336","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Exenatide: improved infarct size, salvage, cardiac function (mixed results in 2 larger trials). Liraglutide: improved salvage, infarct size, LVEF, stroke volume, reduced no-reflow. Both safe. No significant MACE reduction.","whyItMatters":"Limiting heart muscle damage during a heart attack directly impacts long-term survival and quality of life. GLP-1 drugs' cardioprotective properties could be a valuable addition to standard STEMI treatment protocols.","specificNumbers":"","methodology":"Scoping review of 10 studies (RCTs and cohorts) of exenatide and liraglutide in adults with STEMI.","limitations":"Small studies with limited generalizability. Mixed results for exenatide. No significant event-driven outcomes. Short follow-up in most studies."},{"rthcId":"RPEP-13635","title":"Cardiovascular Effects of Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction: A Systematic Review and Meta-Analysis.","authors":"Sobral, Milene Vitória Sampaio; Rodrigues, Livia Kneipp; Barbosa, Abner Mácola Pacheco; da Rocha, Naila Camila; Moulaz, Isac Ribeiro; Dos Santos, João Pedro Pereira; Oliveira, Bruno Henrique Couto; Moreira, João Lucas de Magalhães Leal; Pacagnelli, Francis Lopes; Guida, Camila Mota","year":2025,"journal":"American journal of cardiovascular drugs : drugs, devices, and other interventions, 25(4), 461-467","doi":"10.1007/s40256-025-00721-4","pmid":"39907981","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"6MWD: +16.2m (p<0.001, I²=0%); SBP: -2.22 mmHg (p<0.01, I²=0%); CRP: ratio 0.59 (p<0.001, I²=51%); NT-proBNP: ratio 0.81 (p<0.001, I²=0%). 3 studies, 1,463 patients, 52 weeks.","whyItMatters":"HFpEF is the most common form of heart failure with limited treatment options. Quantifying semaglutide's benefits across multiple outcomes strengthens the case for its use in this condition.","specificNumbers":"","methodology":"Systematic review and meta-analysis of 2 RCTs + 1 non-randomized cohort from EMBASE, PubMed, Cochrane. Random-effects models. 52-week follow-up.","limitations":"Only 3 studies available. Mix of RCTs and observational. CRP showed moderate heterogeneity (I²=51%). No mortality or hospitalization endpoint."},{"rthcId":"RPEP-13636","title":"Exploring beyond numeric weight loss: The metabolic effects of semaglutide.","authors":"Sokary, Sara; Bawadi, Hiba","year":2025,"journal":"Clinical nutrition ESPEN, 67, 435-440","doi":"10.1016/j.clnesp.2025.03.010","pmid":"40107359","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Fat mass: -3.5% total, -2.0% visceral. Lean mass: +3.0% proportion. HbA1c: -1.2-1.8%. LDL: -0.16 mmol/L, total cholesterol: -0.48 mmol/L (unique among GLP-1RAs). Reduced hunger, increased satiety. Weight regain on discontinuation.","whyItMatters":"Scale weight does not capture the full picture. Semaglutide's preferential fat reduction (especially visceral) with lean mass preservation addresses the \"quality\" of weight loss—more important for metabolic health than total kilograms lost.","specificNumbers":"","methodology":"Narrative review of clinical trial data on semaglutide body composition, glycemic, lipid, appetite, and weight maintenance effects.","limitations":"Narrative review. Body composition data from limited studies. Lean mass preservation may partly reflect proportional change, not absolute preservation."},{"rthcId":"RPEP-13637","title":"The promise of tirzepatide: A narrative review of metabolic benefits.","authors":"Sokary, Sara; Bawadi, Hiba","year":2025,"journal":"Primary care diabetes, 19(3), 229-237","doi":"10.1016/j.pcd.2025.03.008","pmid":"40221292","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Weight loss: 5-20.9% (dose-dependent, 72 weeks). Fat mass primary driver. HbA1c: -20.4 to -28.2 mmol/mol. Reduced appetite, increased satiety. Improved cholesterol, LDL, triglycerides, HDL. GI AEs at higher doses; 4-10% discontinuation.","whyItMatters":"Understanding tirzepatide's full metabolic profile—beyond weight loss—helps clinicians and patients make informed treatment decisions and manage expectations.","specificNumbers":"","methodology":"Narrative review of tirzepatide clinical trial data covering weight loss, body composition, appetite, glycemic control, and lipid effects.","limitations":"Narrative review. Trials had specific populations. Long-term (>72 weeks) data limited. Body composition data from limited studies. Weight regain after discontinuation not comprehensively covered."},{"rthcId":"RPEP-13638","title":"Histatin 8 Interactions with Copper, Zinc, and Nickel Ions, and Its Antimicrobial Profile in Relation to Histatin 5.","authors":"Sokołowska, Justyna; Słowik, Joanna; Zamłyńska, Katarzyna; Kutkowska, Jolanta; Lenartowicz, Paweł; Witkowska, Danuta","year":2025,"journal":"Molecules (Basel, Switzerland), 31(1)","doi":"10.3390/molecules31010110","pmid":"41515407","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Hst5: 2 Cu(II) binding sites (Kd 0.2 µM and 14.8 µM). Hst8: 1 Cu(II) binding site (Kd 12.3 µM). Distinct antimicrobial profiles. Different copper binding mechanisms. Both tested against E. coli, S. aureus, C. albicans.","whyItMatters":"Understanding how metal ions modulate antimicrobial peptide activity could enable designing more potent peptide antibiotics by optimizing their metal-binding properties.","specificNumbers":"","methodology":"Isothermal titration calorimetry (ITC) for Cu(II), Zn(II), Ni(II) binding. Antimicrobial assays against E. coli, S. aureus, and 2 C. albicans strains.","limitations":"In vitro study. Metal concentrations used may not reflect salivary conditions. Limited microbial species tested. Functional significance of binding differences for in vivo antimicrobial activity unclear."},{"rthcId":"RPEP-13639","title":"Evaluation of Proopiomelanocortin (POMC) and neuropeptide Y (NPY) levels in bipolar and unipolar patients.","authors":"Solak, Hatice; Gokcen, Onur","year":2025,"journal":"BMC psychiatry, 25(1), 707","doi":"10.1186/s12888-025-07147-x","pmid":"40670972","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"NPY and POMC: significantly lower in both UP and BP vs controls (p=0.001). NPY: lower in UP vs BP (NS). POMC: lower in BP vs UP (NS). No correlation with HAM-D, sleepiness, or eating scales.","whyItMatters":"Identifying neuropeptide biomarkers that are altered in mood disorders could enable objective diagnostic testing and reveal new therapeutic targets, especially given the difficulty of distinguishing bipolar from unipolar depression clinically.","specificNumbers":"","methodology":"Case-control study: 26 UP + 28 BP patients + 27 healthy controls. Serum NPY and POMC quantification. HAM-D, Epworth Sleepiness Scale, Three-Factor Eating Questionnaire.","limitations":"Small sample sizes. Serum levels may not reflect brain neuropeptide concentrations. Cross-sectional—cannot determine causation. Medication effects not fully controlled. No significant differentiation between BP and UP."},{"rthcId":"RPEP-13640","title":"Hypothalamic PNOC/NPY neurons constitute mediators of leptin-controlled energy homeostasis.","authors":"Solheim, Marie H; Stroganov, Sima; Chen, Weiyi; Subagia, P Sicilia; Bauder, Corinna A; Wnuk-Lipinski, Daria; Del Río-Martín, Almudena; Sotelo-Hitschfeld, Tamara; Beddows, Cait A; Klemm, Paul; Dodd, Garron T; Lundh, Sofia; Secher, Anna; Wunderlich, F Thomas; Steuernagel, Lukas; Brüning, Jens C","year":2025,"journal":"Cell, 188(13), 3550-3566.e22","doi":"10.1016/j.cell.2025.04.001","pmid":"40273910","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"PNOC/NPY neurons (non-AgRP) identified in ARC. Lepr deletion in PNOC neurons → hyperphagia + obesity via NPY upregulation. Lepr restoration in PNOC neurons → substantial weight reduction. PNOC/NPY activation promotes feeding = all PNOCARC activation. NPY overexpression in PNOC → hyperphagia + obesity.","whyItMatters":"This discovers a fundamentally new brain circuit for appetite control, distinct from the well-known AgRP/NPY pathway. It reveals a new target for obesity therapeutics and deepens our understanding of how leptin controls body weight.","specificNumbers":"","methodology":"Genetic mouse models: Lepr deletion and restoration in PNOC neurons, chemogenetic (DREADD) activation, NPY overexpression in PNOCARC neurons. Body weight, food intake, gene expression analysis.","limitations":"Mouse study—human PNOC/NPY neurons may differ. Genetic manipulations are artificial. No pharmacological intervention tested. Translation to human obesity uncertain."},{"rthcId":"RPEP-13641","title":"The Immunomodulatory Activity of Thymosin Alpha 1 on Tumor Cell Lines and Distinct Immune Cell Subsets.","authors":"Solmonese, Laura; Lofiego, Maria Fortunata; Fazio, Carolina; Marzani, Francesco; Piazzini, Francesca; Bello, Emma; Celesti, Fabrizio; Giacobini, Gianluca; Wang, Xiaohui; Maio, Michele; Coral, Sandra; Di Giacomo, Anna Maria; Covre, Alessia","year":2025,"journal":"OncoTargets and therapy, 18, 995-1012","doi":"10.2147/OTT.S527785","pmid":"40955371","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Cancer cells: minimal DEGs and immune-related changes after Tα1. Immune cells: significant transcriptional changes in all subsets. Greatest impact: activated CD8+ T cells. Tα1 directly affects immune cell proliferation and transcription.","whyItMatters":"Understanding that Tα1 works through immune activation rather than direct tumor modification is crucial for designing combination immunotherapy strategies—Tα1 should be paired with approaches that enhance tumor antigen presentation.","specificNumbers":"","methodology":"nCounter SPRINT Profiler gene expression analysis of melanoma, glioblastoma, mesothelioma cell lines and HD CD4+ T, CD8+ T, B, NK cells after 48h Tα1 treatment.","limitations":"In vitro only. Gene expression may not reflect protein-level changes. Healthy donor immune cells may respond differently than cancer patient cells. Limited cancer types tested."},{"rthcId":"RPEP-13642","title":"Immune cell uptake of glycinated nanoparticles conjugated to anti-fibrotic peptides enables their prolonged activity and oral administration.","authors":"Somanader-Livera, Deidree V N; Wei, Chen; Wang, Chao; Li, Yifang; Ferens, Dorota; Salimova, Ekaterina; Selomulya, Cordelia; Hossain, Mohammed Akhter; Samuel, Chrishan S; Chakraborty, Amlan","year":2025,"journal":"Journal of biomedical science, 32(1), 104","doi":"10.1186/s12929-025-01198-8","pmid":"41382190","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Glycinated NPs: improved biocompatibility, RLX conjugation maintained. Preferential uptake by monocytes and T cells. Targeted delivery of anti-fibrotic peptide to relevant immune cells.","whyItMatters":"Fibrosis has no cure. Relaxin is a promising anti-fibrotic peptide but has poor pharmacokinetics. Nanoparticle delivery targeting the immune cells that drive fibrosis could make relaxin therapy clinically viable.","specificNumbers":"","methodology":"Nanoparticle synthesis (glycinated poly(styrene-alt-maleic acid)), relaxin conjugation, immune cell uptake studies with monocytes, T cells, and other immune populations.","limitations":"In vitro uptake studies. No in vivo disease model data. Anti-fibrotic efficacy of delivered relaxin not demonstrated. Manufacturing scalability unclear."},{"rthcId":"RPEP-13643","title":"Novel GLP-1-Based Medications for Type 2 Diabetes and Obesity.","authors":"Son, Jang Won; le Roux, Carel W; Blüher, Matthias; Nauck, Michael A; Lim, Soo","year":2025,"journal":"Endocrine reviews","doi":"10.1210/endrev/bnaf036","pmid":"41054801","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Pipeline agents: retatrutide (triple), survodutide/mazdutide (GLP-1/glucagon), CagriSema/amycretin (amylin+GLP-1), maridebart cafraglutide (GIPR antagonist+GLP-1R agonist), danuglipron/orforglipron (oral small molecules). Multiple mechanisms under development.","whyItMatters":"Understanding the next wave of metabolic drugs helps clinicians and patients anticipate future options. Multiple agents in late-stage development could offer even greater efficacy than current best-in-class treatments.","specificNumbers":"","methodology":"Narrative review of clinical development pipeline for novel GLP-1-based agents, excluding approved drugs.","limitations":"Review of agents in development—many may not reach approval. Comparative efficacy data limited. Long-term safety unknown for most agents."},{"rthcId":"RPEP-13644","title":"Acute Deep Vein Thrombosis in the Setting of Tirzepatide Use: A Case Highlighting Emerging Concerns.","authors":"Sonavane, Kunal; Agrawal, Gautam; Agarwal, Bhawna; Parsi, Saketh; Ponnam, Hari Krishna Choudary; Shirsat, Pallavi","year":2025,"journal":"JCEM case reports, 3(12), luaf248","doi":"10.1210/jcemcr/luaf248","pmid":"41179274","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Unprovoked DVT after tirzepatide initiation. Negative hypercoagulability workup. Resolved with anticoagulation + drug discontinuation.","whyItMatters":"Thromboembolic events have not been commonly reported with GLP-1/GIP drugs. This case raises awareness of a potential rare but serious side effect requiring vigilance.","specificNumbers":"","methodology":"Single case report.","limitations":"Single case. Cannot establish causation. DVT may be coincidental. Very rare event."},{"rthcId":"RPEP-13645","title":"Rhabdomyolysis Associated with the Use of Tirzepatide.","authors":"Sonavane, Kunal; Shirsat, Pallavi; Agrawal, Gautam; Agarwal, Bhawna","year":2025,"journal":"European journal of case reports in internal medicine, 12(5), 005392","doi":"10.12890/2025_005392","pmid":"40352714","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"35-year-old, no comorbidities. Tirzepatide for weight loss. Severe rhabdomyolysis. Muscle biopsy: necrotizing myopathy. No other cause identified. Resolved with drug cessation + IV fluids.","whyItMatters":"Rhabdomyolysis can be life-threatening (kidney failure). Recognizing GLP-1/GIP drugs as a potential cause enables earlier diagnosis and treatment, especially in otherwise healthy young patients.","specificNumbers":"","methodology":"Case report with muscle biopsy confirmation.","limitations":"Single case. Cannot prove causation definitively. Rhabdomyolysis has many potential causes. Mechanism of tirzepatide-induced myopathy unknown."},{"rthcId":"RPEP-13646","title":"The GLP1R Agonist Semaglutide Inhibits Reactive Astrocytes and Enhances the Efficacy of Neural Stem Cell Transplantation Therapy in Parkinson's Disease Mice.","authors":"Song, Dan; Zou, Xiaoya; Ma, Di; Zhao, Yuying; Liu, Tingting; Shen, Bibiao; Cheng, Oumei","year":2025,"journal":"Advanced science (Weinheim, Baden-Wurttemberg, Germany), 12(43), e17664","doi":"10.1002/advs.202417664","pmid":"40874950","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide + NSCs: improved motor function. NSC survival: 3.258 vs 0.819 × 10⁻¹¹ photon flux (4x improvement). Reduced C3+ reactive astrocytes. RNA-seq: inflammatory factors in C3+ astrocytes hinder NSC differentiation. Semaglutide every other day for 4 weeks.","whyItMatters":"Cell transplantation for PD has been limited by poor transplanted cell survival. Using semaglutide to create a more hospitable brain environment could make stem cell therapy much more effective.","specificNumbers":"","methodology":"6-OHDA-induced PD mouse model. Midbrain-derived NSC transplantation into striatum. Semaglutide every other day for 4 weeks. In vivo fluorescence imaging. Astrocyte phenotyping. Co-culture experiments. RNA-seq.","limitations":"Mouse model. Small time window (4 weeks). Specific semaglutide dose for brain effects may differ from metabolic doses. Long-term transplant survival not assessed."},{"rthcId":"RPEP-13647","title":"Novel Cholecystokinin Secretion-Stimulating Peptides from Oat Protein Hydrolysate: Sequence Identification and Insight into the Mechanism of Action.","authors":"Song, Hongdong; Xue, Lei; Fu, Qiuyun; Wang, Haiyan; Cao, Hongwei; Huang, Kai; Guan, Xiao","year":2025,"journal":"Journal of agricultural and food chemistry, 73(18), 10998-11006","doi":"10.1021/acs.jafc.5c00727","pmid":"40275796","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"4 novel CCK-stimulating peptides identified from oat. QGDVVALPA most potent. Mechanism: calcium-sensing receptor → Gq → intracellular Ca²⁺ → CaMKII → CCK secretion. OPH increased plasma CCK in mice.","whyItMatters":"Natural appetite control through food-derived peptides could complement pharmacological weight management. Identifying specific peptides and their signaling mechanism enables targeted functional food development.","specificNumbers":"","methodology":"Simulated GI digestion, mouse intragastric administration, SEC and LC-MS/MS peptide identification, STC-1 cell CCK secretion assays, receptor inhibition studies.","limitations":"Mouse study. Specific peptide doses in food matrix unclear. Bioavailability of individual peptides in humans unknown. CCK stimulation is one of many satiety mechanisms."},{"rthcId":"RPEP-13648","title":"Peptide vaccine formulations with structurally distinct STING agonist drugamers induce discrete, efficacious antitumor responses.","authors":"Song, Kefan; Nguyen, Dinh Chuong; Wang, Yonghui; Jokonya, Simbarashe; Yazdani, Omeed; Sellers, Drew L; Stayton, Patrick S; Pun, Suzie H","year":2025,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 122(45), e2409978122","doi":"10.1073/pnas.2409978122","pmid":"41183196","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Both VIPER-STING drugamers enhanced DC maturation and CD8+ T cell responses. polySTING: more tumor-infiltrating CD8+ T cells. NPSTING: more LN antigen-presenting DCs. Both: efficacy in B16-OVA melanoma and MC38 colon cancer. Combination with anti-PD-1: tumor remission + immunity in subset.","whyItMatters":"Peptide cancer vaccines have struggled in clinical translation due to poor immunogenicity. This platform solves two key problems: endosomal escape (VIPER) and innate immune activation (STING drugamers), achieving the elusive goal of peptide vaccine-mediated tumor remission.","specificNumbers":"","methodology":"Peptide vaccine platform (VIPER) with 2 STING drugamer structures. B16-OVA melanoma and MC38 colon cancer mouse models. DC maturation, CD8+ T cell assays, combination with anti-PD-1.","limitations":"Mouse models only. Remission in subset of mice (not all). STING agonists can cause systemic toxicity. Manufacturing complexity of polymer-peptide-drugamer system. Human translation uncertain."},{"rthcId":"RPEP-13649","title":"Comparative effects of SGLT2 inhibitors and incretin-based therapies on dementia risk in type 2 diabetes: a systematic review and meta-analysis.","authors":"Song, Kirim; Choi, Jiwon; Jeong, Dayeon; Shin, Dongyun; Ah, Young-Mi; Lee, Ki Young; Choi, Kyung Hee","year":2025,"journal":"Frontiers in endocrinology, 16, 1695075","doi":"10.3389/fendo.2025.1695075","pmid":"41234238","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"SGLT2i vs incretins overall: HR 0.82. vs DPP-4i: HR 0.67. vs GLP-1RA: HR 0.93. Vascular dementia: HR 0.49. Alzheimer's: HR 0.68. Greater benefit in >65. Empagliflozin most protective.","whyItMatters":"Dementia affects millions of diabetics. Knowing that drug choice influences dementia risk could shift prescribing patterns—particularly favoring SGLT2 inhibitors for older diabetic patients at cognitive risk.","specificNumbers":"","methodology":"Systematic review and meta-analysis of PubMed, Embase, Cochrane through Feb 2025. 9 cohort studies. PROSPERO registered.","limitations":"Only cohort studies (no RCTs). Potential confounding. Dementia diagnosis methods may vary. SGLT2i vs GLP-1RA comparison barely significant. Cannot determine mechanism."},{"rthcId":"RPEP-13650","title":"Effects of new hypoglycemic drugs on patients with heart failure: a systematic review and network meta-analysis.","authors":"Song, Ruirui; Liu, Fang; Shi, Xiaojing; Sun, Songtao; Chen, Jun; Gao, Hongmei","year":2025,"journal":"Postgraduate medical journal, 101(1194), 330-350","doi":"10.1093/postmj/qgae148","pmid":"39487697","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1RA > SGLT2i for LVEF and MI/ACS reduction. DPP-4i > SGLT2i for LVEDV and LVESV. Dapagliflozin/empagliflozin: best for HF rehospitalization vs liraglutide. Albiglutide: lowest CV death vs exenatide. Dose-dependent effects documented.","whyItMatters":"This is the first NMA comparing all three diabetes drug classes head-to-head at specific dose levels for heart failure outcomes, enabling more precise treatment selection based on the specific cardiac benefit needed.","specificNumbers":"","methodology":"Comprehensive systematic review and network meta-analysis of SGLT2i, GLP-1RA, DPP-4i at different doses for heart failure patients.","limitations":"Network meta-analysis with indirect comparisons. Heterogeneous study populations and follow-up durations. Some comparisons based on few studies. DPP-4i results surprising and need verification."},{"rthcId":"RPEP-13651","title":"Liraglutide Attenuates Disease Severity in Experimental Autoimmune Encephalomyelitis by Modulating Splenic T Helper Cell Subsets.","authors":"Song, Shuang; Li, Bin; Guo, Ruoyi; Zhou, Yi; Xue, Yumei; Guo, Li","year":2025,"journal":"Brain and behavior, 15(11), e71074","doi":"10.1002/brb3.71074","pmid":"41251049","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Max clinical score: 2.50 (EAE) vs 1.75 (EAE+liraglutide), p=0.005. Th1 cells: 11.95%→5.94% with liraglutide (p=0.025). Treg: no significant change. Body weight: no significant difference. n=10 per treatment group.","whyItMatters":"This provides the first direct evidence that a GLP-1 drug modifies MS-like disease through specific immune cell modulation (Th1 suppression), moving beyond general anti-inflammatory effects to a defined immunological mechanism.","specificNumbers":"","methodology":"EAE induced in C57BL/6 mice via MOG immunization. 3 groups: control (n=8), EAE (n=10), EAE+liraglutide (n=10). Liraglutide 10 µg/kg SC every other day from day 8. Flow cytometry of splenocytes at day 20.","limitations":"Preliminary study with small groups (n=10). Only splenic T cells analyzed—brain-infiltrating cells not assessed. Treg effect may need longer treatment. EAE is a simplified MS model."},{"rthcId":"RPEP-13652","title":"Hazelnut-Derived Peptide YYLLVR Improves Endothelial Dysfunction in Hypertension by Activating ACE2.","authors":"Song, Wentian; Huang, Haoduo; Shen, Yue; Wu, Dan; Fang, Li; Liu, Xiaoting; Xu, Yu; Wang, Chongchong; Zhao, Fanrui; Liu, Chunlei; Min, Weihong","year":2025,"journal":"Journal of agricultural and food chemistry, 73(27), 17024-17039","doi":"10.1021/acs.jafc.5c04776","pmid":"40522957","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"YYLLVR: SBP -53.48 mmHg, DBP -37.57 mmHg. ACE2 expression increased 2-fold. Endothelial dysfunction markers improved (p<0.05 for multiple endpoints). Tested in SHR model.","whyItMatters":"Identifying a food-derived peptide that activates ACE2 (rather than blocking ACE) represents a novel antihypertensive mechanism. ACE2 converts harmful angiotensin II to protective ang-(1-7).","specificNumbers":"","methodology":"Spontaneously hypertensive rat (SHR) model. YYLLVR peptide administration with BP monitoring, ACE2 expression analysis, and endothelial function assessment.","limitations":"Short abstract—limited methodological detail. Animal study only. Bioavailability of oral YYLLVR in humans unknown. Very large BP reductions need confirmation."},{"rthcId":"RPEP-13653","title":"Trigeminal nerve-driven neurogenic inflammation linking migraine to glioblastoma invasion: a literature review.","authors":"Song, Xiaoli; Zhu, Qian; Zhang, Jieying; Yang, Jin; Zhang, Xinxin; Song, Qian","year":2025,"journal":"Frontiers in immunology, 16, 1632154","doi":"10.3389/fimmu.2025.1632154","pmid":"40740778","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CGRP and SP upregulate MMPs and integrins in GBM. PACAP modulates cAMP-MAPK signaling. GBM spreads along trigeminal pathways on MRI. Aprepitant: GBM apoptosis. Gepants: reduce GBM invasion. Radiolabeled SP: focal alpha-therapy. Epidemiological: higher migraine antecedents in brain tumor patients.","whyItMatters":"This reveals that migraine drugs could be repurposed for brain cancer treatment—a completely unexpected therapeutic connection with immediate translational potential since these drugs already exist.","specificNumbers":"","methodology":"Comprehensive literature review integrating neurobiology, oncology, and pharmacology evidence for trigeminal neurogenic inflammation in GBM.","limitations":"Review based on correlative and preclinical evidence. Epidemiological link needs stronger studies. Drug repurposing potential is based on preclinical data. Mechanisms largely demonstrated in vitro."},{"rthcId":"RPEP-13654","title":"The potential applications of peptide-loading complex in cancer treatment.","authors":"Song, Zhidu; Tao, Ying; You, Jiaxin","year":2025,"journal":"Frontiers in immunology, 16, 1526137","doi":"10.3389/fimmu.2025.1526137","pmid":"40098955","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"PLC coordinates MHC-I peptide loading (calreticulin, tapasin, ERp57, TAP). Tumor immune evasion through PLC component downregulation → reduced MHC-I. MHC-I loss → resistance to checkpoint inhibitors and adoptive T cell therapy. Restoring PLC function could overcome immune evasion.","whyItMatters":"Many cancer patients fail to respond to immunotherapy because their tumors hide from the immune system by reducing MHC-I. Understanding the PLC—the machinery that loads peptides for immune recognition—reveals new therapeutic targets to make tumors visible again.","specificNumbers":"","methodology":"Narrative review of PLC structure, function, and role in cancer immune evasion and immunotherapy response.","limitations":"Narrative review. Most PLC restoration strategies are conceptual. In vivo evidence for therapeutic PLC modulation is limited. Tumor heterogeneity in PLC expression complicates targeting."},{"rthcId":"RPEP-13655","title":"Pharmacogenomics of Tirzepatide: Genomic Insights into Dual GIP/GLP-1 Agonist Response in Type 2 Diabetes and Atherosclerosis.","authors":"Song, Zihang; Tang, Yifan; Peng, Mao; Han, Ruoyu; He, Pingping","year":2025,"journal":"Pharmaceuticals (Basel, Switzerland), 18(9)","doi":"10.3390/ph18091261","pmid":"41011133","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Pharmacogenomic variants in GIP/GLP-1 receptor pathways influence tirzepatide response. Genetic susceptibility genes for T2DM and AS overlap with drug response pathways. Precision subtyping potential for individualized therapy.","whyItMatters":"Not everyone responds equally to tirzepatide. Understanding the genetic basis of response variability could enable prescribers to identify the right patients for the right drug at the right dose—the goal of precision medicine.","specificNumbers":"","methodology":"Systematic narrative review of pharmacogenomic variants, drug response genes, and genetic susceptibility data for tirzepatide, T2DM, and atherosclerosis.","limitations":"Review without primary data. Many proposed pharmacogenomic associations are theoretical. Clinical validation of genetic predictors is lacking."},{"rthcId":"RPEP-13656","title":"Adropin as a Marker in Type 2 Diabetes: Insights Into Diabetic Kidney Disease and Chronic Heart Failure.","authors":"Sonkar, Satyendra K; Agrawal, Madhusudan; Sonkar, Gyanendra K; Bhosale, Vivek; Gautam, Medhavi; Pradhan, Akshay; Kumar, Satish; Bhagchandani, Deepak; Singh, Abhishek","year":2025,"journal":"Cureus, 17(9), e91572","doi":"10.7759/cureus.91572","pmid":"41054696","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Adropin: 0.61 ng/mL in T2DM (p significant vs controls). Correlations: HbA1c (r=-0.31), ACR (r=-0.59), CRP (r=-0.37), NT-proBNP (r=-0.44), eGFR (r=+0.31). AUC: DKD 0.946, DKD+CHF 0.965, T2DM+CHF 0.887.","whyItMatters":"Adropin could become a single blood test that predicts diabetic kidney and heart complications—two of the most important causes of death in diabetes. Its high diagnostic accuracy suggests clinical utility.","specificNumbers":"","methodology":"Observational case-control study. 111 participants in 3 groups. Serum adropin by ELISA. Clinical, biochemical, echocardiographic assessment. ROC analysis.","limitations":"Small study (111 participants). Cross-sectional—cannot determine if adropin decline is cause or consequence. Single-center. Adropin assays not yet standardized."},{"rthcId":"RPEP-13657","title":"Vasoactive Intestinal Peptide: Another Player in Adipose Tissue Blood Flow Regulation?","authors":"Sotorník, Richard; Ménard, Julie; Brassard, Pascal; Gagnon-Auger, Maude; Baillargeon, Jean-Patrice; Ardilouze, Jean-Luc","year":2025,"journal":"Microcirculation (New York, N.Y. : 1994), 32(7), e70026","doi":"10.1111/micc.70026","pmid":"40946317","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"VIP microinfusion dose-dependently increased ATBF: 2.67→4.35→7.91 mL/100g/min (p<0.0001). 7/16 were non-responders to glucose ATBF. Non-responders: trend toward lower VIP response (NS). Oral glucose: no change in plasma VIP.","whyItMatters":"Poor adipose tissue blood flow after eating is linked to metabolic syndrome. If VIP signaling is impaired in non-responders, it could explain why some people develop cardiometabolic risk factors despite normal weight and diet.","specificNumbers":"","methodology":"16 healthy participants. 75g oral glucose tolerance test with plasma VIP and ATBF (133-Xenon washout). 12 participants: local VIP microinfusion at 3 doses.","limitations":"Very small study (n=16). Non-responder comparison non-significant. Local VIP infusion may not reflect physiological concentrations. Single measurement point."},{"rthcId":"RPEP-13658","title":"Unlocking the Therapeutic Potential of Cyclic Peptide-Based Nanocarriers for Enhanced Colon Cancer Treatment.","authors":"Souresh, Vedhapriya; Srikayalsamyukktha, M; Harini, M; Saravanan, Yudhesh; Saravanakumar, Rupachandra","year":2025,"journal":"The protein journal, 44(6), 691-716","doi":"10.1007/s10930-025-10289-2","pmid":"41047440","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Cyclic peptides: structural stability, enhanced bioavailability, target specificity. Nanocarrier types: liposomes, niosomes, nanosponges, nanopolymers. Benefits: targeted delivery, controlled release, drug resistance overcome. Sources: plant, marine, microbial.","whyItMatters":"Colon cancer is a leading cause of cancer death, and drug resistance limits treatment. Cyclic peptide nanocarriers address both challenges: natural anticancer activity plus smart delivery to overcome resistance.","specificNumbers":"","methodology":"Comprehensive narrative review of cyclic peptide sources, mechanisms, therapeutic applications, and nanocarrier integration for colon cancer.","limitations":"Review of primarily preclinical data. Clinical translation of cyclic peptide nanocarriers is early. Manufacturing complexity and cost unknown. In vivo efficacy data limited."},{"rthcId":"RPEP-13659","title":"Obesity and Pancreatic Diseases: From Inflammation to Oncogenesis and the Impact of Weight Loss Interventions.","authors":"Souto, Mariana; Cúrdia Gonçalves, Tiago; Cotter, José","year":2025,"journal":"Nutrients, 17(14)","doi":"10.3390/nu17142310","pmid":"40732935","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Obesity mechanisms in pancreatic disease: gallstone formation, hypertriglyceridemia, lipotoxicity, intrapancreatic fat, inflammation, adipokine imbalance, oncogenic signaling. GLP-1RAs and tirzepatide: promising weight loss interventions reducing disease burden. Paradoxical protective effect in CP.","whyItMatters":"Pancreatic cancer has the worst prognosis of common cancers. Understanding obesity as a modifiable risk factor—and that GLP-1 drugs may reduce this risk—could have major public health impact.","specificNumbers":"","methodology":"Narrative review of clinical, epidemiological, and mechanistic studies on obesity-pancreatic disease relationship and weight loss interventions.","limitations":"Narrative review. Causal links between GLP-1 drugs and reduced pancreatic disease risk not yet established. Paradoxical CP finding needs clarification."},{"rthcId":"RPEP-13660","title":"Comparison of pharmacological therapies in metabolic dysfunction-associated steatohepatitis for fibrosis regression and MASH resolution: Systematic review and network meta-analysis.","authors":"Souza, Matheus; Al-Sharif, Lubna; Antunes, Vanio L J; Huang, Daniel Q; Loomba, Rohit","year":2025,"journal":"Hepatology (Baltimore, Md.), 82(6), 1523-1533","doi":"10.1097/HEP.0000000000001254","pmid":"39903735","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Fibrosis regression top SUCRA: pegozafermin (79.92), cilofexor+firsocostat (71.38). MASH resolution top SUCRA: pegozafermin (91.75), survodutide (90.87), tirzepatide (84.70). 8 agents better than placebo for fibrosis; 12 for resolution. 29 RCTs, 9,324 patients.","whyItMatters":"With multiple MASH drugs in development, clinicians and trialists need to know which are most effective. This ranking shows peptide-based drugs (tirzepatide, semaglutide, survodutide, liraglutide) among the top performers.","specificNumbers":"","methodology":"Network meta-analysis of PubMed/Embase (Jan 2020-Dec 2024). 29 RCTs, 9,324 patients with biopsy-proven MASH. SUCRA ranking for co-primary endpoints.","limitations":"NMA relies on indirect comparisons. Different trial durations and populations. Biopsy endpoints are imperfect. Not all agents have phase 3 data."},{"rthcId":"RPEP-13661","title":"Neuroimmune interactions in arthritis: linking pain sensitisation and inflammation.","authors":"Sow, Tammie Tao Min; Hasegawa, Tetsuo","year":2025,"journal":"Journal of bone and mineral metabolism","doi":"10.1007/s00774-025-01678-9","pmid":"41454032","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Sensory nerves release CGRP and SP → modulate macrophages and immune cells. Macrophage IL-1β, IL-6, TNF-α → sensitize nociceptors. CCL2 → engages neuronal receptors for excitability. Sympathetic signaling → immune modulation. Synovial remodeling: nerve sprouting + immune infiltration.","whyItMatters":"Arthritis pain is often undertreated because current therapies target either inflammation or pain but not both. Understanding the neuroimmune feedback loop reveals dual-target therapeutic opportunities using neuropeptide-targeting drugs.","specificNumbers":"","methodology":"Narrative review of neuroimmune interactions in arthritis, integrating synovial biology, neuropeptide signaling, and macrophage-neuron crosstalk.","limitations":"Narrative review. Most mechanistic data from animal models. Clinical evidence for neuropeptide-targeted arthritis therapy is limited."},{"rthcId":"RPEP-13662","title":"Dipyrone induces sex-dependent latent sensitization in a preclinical model of medication overuse headache.","authors":"Spagnol, Fernanddo José; Zortea, Julia Maria; Gomes, Larissa Cieslinsky; da Luz, Fernanda Mariano Ribeiro; Baggio, Darciane Favero; Lejeune, Vanessa Bordenowsky Pereira; Ferreira, Luiz Eduardo Nunes; Kopruszinski, Caroline Machado; Chichorro, Juliana Geremias","year":2025,"journal":"European journal of pharmacology, 1006, 178173","doi":"10.1016/j.ejphar.2025.178173","pmid":"40962013","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Acute dipyrone reduced CGRP-induced allodynia in both sexes. Chronic dipyrone (30 days): latent sensitization in females only (revealed by bright light). No effect on paw threshold, locomotion, or plasma CGRP. Sex-dependent vulnerability.","whyItMatters":"MOH affects millions worldwide, predominantly women. This provides the first preclinical evidence that a widely used analgesic causes sex-specific trigeminal sensitization, supporting the clinical observation of female vulnerability to MOH.","specificNumbers":"","methodology":"Rat model: trigeminal CGRP injection (0.1 nmol) for acute testing. Chronic: dipyrone 120 mg/kg 2x/day for 30 days. Periorbital mechanical threshold, bright light challenge, hindpaw assessment, locomotion, plasma CGRP.","limitations":"Animal model may not fully replicate human MOH. Single analgesic tested. CGRP plasma may not reflect brain levels. Mechanism of sex difference not elucidated."},{"rthcId":"RPEP-13663","title":"The effect of Semaglutide on mitochondrial function and insulin sensitivity in a myotube model of insulin resistance.","authors":"Spry, Emmalie R; Travis, Kipton B; Ragland, Kayla J; Klein, Alexa J; Zimmerman, John M; Vaughan, Roger A","year":2025,"journal":"Molecular and cellular endocrinology, 608, 112629","doi":"10.1016/j.mce.2025.112629","pmid":"40752656","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide directly activated GLP-1R on myotubes. Improved mitochondrial respiration in insulin-resistant cells. Enhanced insulin-stimulated glucose uptake. Effects independent of weight loss (cell culture model).","whyItMatters":"The debate about whether GLP-1 drugs benefit metabolically through weight loss alone or have direct cellular effects is critical. This study proves direct muscle cell benefits, suggesting GLP-1 drugs improve metabolism even before significant weight is lost.","specificNumbers":"","methodology":"In vitro insulin-resistant myotube model. Semaglutide treatment. GLP-1R expression and activation. Mitochondrial respiration (Seahorse). Insulin-stimulated glucose uptake.","limitations":"In vitro cell model—cannot capture whole-body physiology. Myotube model may not fully represent mature skeletal muscle. Dose may not reflect clinical exposure. Long-term effects unknown."},{"rthcId":"RPEP-13664","title":"The new bridge to hernia surgery: achieving preoperative weight optimization with GLP-1 receptor agonists for abdominal wall hernia repair.","authors":"Spurzem, Graham J; Broderick, Ryan C; Ruiz-Cota, Patricia; Rocha, Amanda; Reyes, Edgardo; Fontaine-Nicola, Andres; Altolaguirre, Agustina; Hollandsworth, Hannah M; Sandler, Bryan J; Grunvald, Eduardo; Jacobsen, Garth R","year":2025,"journal":"Surgical endoscopy, 39(8), 5296-5302","doi":"10.1007/s00464-025-11921-z","pmid":"40603614","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1RAs achieved clinically significant preoperative weight loss in obese hernia patients. Enabled surgical candidacy for previously ineligible patients. Potential to reduce obesity-related surgical complications.","whyItMatters":"Many obese patients are denied hernia repair due to high complication risk. GLP-1 drugs provide the first effective pharmacological bridge to safe surgery, addressing a common clinical impasse.","specificNumbers":"","methodology":"Retrospective study examining GLP-1RA use for preoperative weight optimization before abdominal wall hernia repair.","limitations":"Retrospective. Specific weight loss amounts not detailed in preview. Long-term surgical outcomes not assessed. Small sample likely."},{"rthcId":"RPEP-13665","title":"Factors associated with weight loss response to GLP-1 analogues for obesity treatment: a retrospective cohort analysis.","authors":"Squire, Peter; Naude, James; Zentner, Ali; Bittman, Jesse; Khan, Nadia","year":2025,"journal":"BMJ open, 15(1), e089477","doi":"10.1136/bmjopen-2024-089477","pmid":"39819958","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Average TBWL: 12.2%. Hyper-responders (>15%): 33.8%. Non-responders (<5%): 17.8%. Female sex → hyper-response OR 1.92 (p=0.048). No association: diabetes, BMI, age, sedentary status, anxiety, depression.","whyItMatters":"Predicting who will respond best to expensive GLP-1 drugs is crucial for personalized prescribing. Finding that sex is the only significant predictor while common clinical factors are not challenges current assumptions.","specificNumbers":"","methodology":"Retrospective cohort of 483 adults (BMI ≥30) on semaglutide/liraglutide with ≥6 month follow-up (mean 17.3 months) at Vancouver obesity clinic. Multivariable logistic regression.","limitations":"Retrospective. Canadian population. Multiple GLP-1 drugs pooled. OR for female sex just barely significant (CI 1.01-3.65). Novel biomarkers not assessed."},{"rthcId":"RPEP-13666","title":"Comparative Analysis of CGRP, VIP and 
PACAP-38 Levels in Migraine with and 
Without Aura: A Case-control Study.","authors":"Sreevani, N; Ramesh, B; Maheshkumar, K; Thanalakshmi, J","year":2025,"journal":"Annals of neurosciences, 09727531251340156","doi":"10.1177/09727531251340156","pmid":"40458768","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"All three neuropeptides (CGRP, VIP, PACAP-38) significantly elevated in migraine vs controls (p<0.001). MA > MO for all three. MA trends: higher attack frequency (p=0.06), HIT-6 (p=0.08). 296 participants.","whyItMatters":"While anti-CGRP drugs dominate migraine treatment, this study shows VIP and PACAP-38 are equally elevated. Multi-target approaches blocking multiple neuropeptides could provide better migraine control than single-target therapies.","specificNumbers":"","methodology":"Case-control study: 101 MA + 98 MO + 97 HC. Serum ELISA for CGRP, VIP, PACAP-38. Clinical assessment: attack frequency, HIT-6.","limitations":"Serum levels may not reflect brain concentrations. Interictal measurements. Cross-sectional. Predominantly female sample. Effect sizes not detailed."},{"rthcId":"RPEP-13667","title":"Kisspeptin-10 Ameliorates Obesity-Diabetes with Diverse Effects on Ileal Enteroendocrine Cells and Pancreatic Islet Morphology in High-Fat Fed Female Mice.","authors":"Sridhar, Ananyaa; Khan, Dawood; Muthukumar, Rithiga; Sampathkumar, Swetha; Irwin, Nigel; Flatt, Peter R; Moffett, R Charlotte","year":2025,"journal":"Biomolecules, 15(11)","doi":"10.3390/biom15111591","pmid":"41301510","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Kisspeptin-10: normalized body weight, glucose, energy intake. Increased GIP+ and GLP-1+ gut cells. Restored villi length, crypt depth. Restored insulin area and glucagon radius. Increased beta-cell proliferation. Enhanced FSH and LH. 21-day treatment, 25 nmol/kg IP.","whyItMatters":"This discovers a new metabolic function for kisspeptin that bridges reproductive and metabolic biology. By modulating both gut incretin cells and pancreatic beta-cells, kisspeptin could become a novel therapeutic target for obesity-diabetes.","specificNumbers":"","methodology":"High-fat diet obese diabetic female C57BL/6 mice. Kisspeptin-10 25 nmol/kg IP twice daily for 21 days. Immunohistochemistry for gut hormones and islet morphology. Hormonal profiling.","limitations":"Mouse study only. Female mice only. Short treatment (21 days). IP injection not practical for humans. Dose optimization not explored. Mechanism of gut cell effects unclear."},{"rthcId":"RPEP-13668","title":"Expanding therapeutic horizons: glucagon-like peptide-1 receptor agonists and sodium glucose transporter-2 inhibitors in poly cystic ovarian syndrome: a comprehensive review including systematic review and network meta-analysis of randomized clinical trials.","authors":"Sridharan, Kannan; Sivaramakrishnan, Gowri","year":2025,"journal":"Diabetology & metabolic syndrome, 17(1), 168","doi":"10.1186/s13098-025-01730-8","pmid":"40410888","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1RAs: improved menstrual frequency, weight, FAI, free testosterone, androstenedione, SHBG, triglycerides, insulin resistance, glucose. SGLT2is: improved FAI, total testosterone, WHR, AGF, HOMA-IR (outperformed GLP-1 for FAI, testosterone, LDL, HOMA-IR). Combination > monotherapy for weight, fat, triglycerides, glucose. 27 RCTs, 1,642 patients.","whyItMatters":"PCOS affects 5-15% of reproductive-age women with limited treatment options. This is the most comprehensive comparison of GLP-1 and SGLT2 drugs for PCOS, revealing distinct strengths that support personalized treatment selection.","specificNumbers":"","methodology":"Systematic review and network meta-analysis of 27 RCTs (1,642 participants). Random-effects NMA. Plus systematic review of preclinical studies.","limitations":"Very low evidence quality (GRADE). NMA indirect comparisons. Heterogeneous PCOS definitions and outcomes. Short trial durations. Limited fertility outcome data."},{"rthcId":"RPEP-13669","title":"Managing post-bariatric hypoglycemia: a systematic review of pharmacological therapies.","authors":"Sridharan, Kannan; Sivaramakrishnan, Gowri","year":2025,"journal":"Diabetology & metabolic syndrome, 17(1), 404","doi":"10.1186/s13098-025-01988-y","pmid":"41126373","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Anakinra: RR 0.29 (95% CI 0.09-0.91). Empagliflozin: RR 0.29. Dasiglucagon: effective rescue. Pasireotide + acarbose: 100% prevention in single-arm studies. Liraglutide, verapamil, semaglutide: variable in case reports. 13 comparative + 5 single-arm + 15 case reports.","whyItMatters":"PBH causes dangerous hypoglycemia in post-bariatric patients and has no established treatment guidelines. This is the first systematic comparison of all pharmacological options, highlighting peptide-based therapies (anakinra, dasiglucagon, pasireotide) among the most promising.","specificNumbers":"","methodology":"Systematic review and mixed treatment comparison per PRISMA. MEDLINE, Cochrane, Google Scholar. 33 studies total. RR meta-analysis. GRADE assessment.","limitations":"Very low evidence quality (GRADE). Small sample sizes. Heterogeneous PBH definitions. Most data from small RCTs or case reports. No long-term data."},{"rthcId":"RPEP-13670","title":"GLP-1 Therapeutics and Their Emerging Role in Alcohol and Substance Use Disorders: An Endocrinology Primer.","authors":"Srinivasan, Nirupam M; Farokhnia, Mehdi; Farinelli, Lisa A; Ferrulli, Anna; Leggio, Lorenzo","year":2025,"journal":"Journal of the Endocrine Society, 9(11), bvaf141","doi":"10.1210/jendso/bvaf141","pmid":"41081017","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1RAs interact with dopaminergic, GABAergic, and opioidergic addiction pathways. Preclinical + early clinical evidence for reducing alcohol and substance use. Already approved for T2DM, obesity, and OSA—enabling rapid evaluation for ASUDs.","whyItMatters":"Addiction treatment has extremely limited pharmacotherapy options. GLP-1 drugs represent the most promising new drug class for ASUDs in decades, with a biological rationale spanning multiple addiction pathways.","specificNumbers":"","methodology":"Narrative review covering ASUD biology, GLP-1RA neurobiological mechanisms in addiction, and emerging clinical evidence.","limitations":"Narrative review. Most evidence preclinical. Clinical addiction trials are small and early. Optimal dosing for addiction unknown. Not FDA-approved for this use."},{"rthcId":"RPEP-13671","title":"Efficacy of Dual Glucagon and Glucagon-like Peptide-1 Receptor Agonists Across the Cardiometabolic Continuum: A Review of Current Clinical Evidence.","authors":"Stachteas, Panagiotis; Nasoufidou, Athina; Karakasis, Paschalis; Koiliari, Markella; Karagiannidis, Efstratios; Koufakis, Theocharis; Fragakis, Nikolaos; Patoulias, Dimitrios","year":2025,"journal":"Reviews in cardiovascular medicine, 26(7), 39691","doi":"10.31083/RCM39691","pmid":"40776973","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Dual Gcg/GLP-1 agonists: GLP-1 reduces appetite + glucagon increases energy expenditure. Benefits across obesity, T2DM, MASLD/MASH, CVD. Survodutide: significant weight loss + liver fat reduction. Mazdutide: weight + glycemic benefits. Glucagon component adds thermogenesis and hepatic fat clearance.","whyItMatters":"Pure GLP-1 drugs suppress appetite but do not increase energy expenditure. Adding glucagon agonism creates a \"burn more, eat less\" dual mechanism that could achieve superior metabolic outcomes.","specificNumbers":"","methodology":"Narrative review of clinical evidence for dual glucagon/GLP-1 receptor agonists across cardiometabolic conditions.","limitations":"Review of emerging clinical data. Most agents in mid-stage development. Long-term safety of glucagon agonism unknown. Glucagon could theoretically worsen glycemia."},{"rthcId":"RPEP-13672","title":"A Snake Toxin Derivative for Treatment of Hyponatremia and Polycystic Kidney Diseases.","authors":"Stanajic-Petrovic, Goran; Keck, Mathilde; Barbe, Peggy; Urman, Apolline; Correia, Evelyne; Isnard, Pierre; Duong Van Huyen, Jean-Paul; Chmeis, Khawla; Diarra, Sékou Siramakan; Palea, Stefano; Theodoro, Frederic; Nguyen, Anvi-Laëtitia; Castelli, Florence; Pruvost, Alain; Zhao, Wenchao; Mendre, Christiane; Mouillac, Bernard; Bienaimé, Frank; Robin, Philippe; Kessler, Pascal; Llorens-Cortes, Catherine; Servent, Denis; Nozach, Hervé; Maillère, Bernard; Guo, Dong; Truillet, Charles; Gilles, Nicolas","year":2025,"journal":"Journal of the American Society of Nephrology : JASN, 36(2), 181-192","doi":"10.1681/ASN.0000000505","pmid":"39431458","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"MQ232: low acute/chronic toxicity. Strong kidney biodistribution. Pure aquaretic effect (water only, no electrolytes). Improved kidney histology in PKD mouse model. Derived from snake toxin with disulfide-bond reticulation.","whyItMatters":"Hyponatremia affects millions of hospitalized patients and PKD has no cure. A kidney-targeted peptide that removes water without electrolyte loss addresses a critical therapeutic gap.","specificNumbers":"","methodology":"Peptide optimization from snake toxin. Toxicology in rats. Biodistribution in mice. Aquaretic efficacy assessment. PKD mouse model histology.","limitations":"Preclinical only. PKD model results are histological, not functional. Human pharmacokinetics unknown. Manufacturing of disulfide-bonded peptides can be challenging."},{"rthcId":"RPEP-13673","title":"Glucagon-Like Peptide-1 Agonists: A Practical Overview for Plastic and Reconstructive Surgeons.","authors":"Stanton, Eloise W; Manasyan, Artur; Banerjee, Rakhi; Hong, Kurt; Koesters, Emma; Daar, David A","year":2025,"journal":"Annals of plastic surgery, 94(1), 121-127","doi":"10.1097/SAP.0000000000004089","pmid":"39293069","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 considerations for plastic surgery: delayed gastric emptying (anesthesia risk), wound healing effects, facial volume loss requiring restoration, body contouring timing, medication hold protocols. Covers all major GLP-1 drugs.","whyItMatters":"As millions take GLP-1 drugs, plastic surgeons increasingly encounter these patients. Understanding drug interactions with surgery is essential for patient safety and optimal cosmetic outcomes.","specificNumbers":"","methodology":"Practical narrative review for plastic surgeons covering GLP-1 drug mechanisms, surgical implications, and management recommendations.","limitations":"Practical guidance based on limited evidence. Most recommendations are expert opinion. Surgical outcome data for GLP-1 patients is scarce."},{"rthcId":"RPEP-13674","title":"Allodynia (skin tenderness) associated with semaglutide: A case series.","authors":"Stark, Jennifer; Klass, Marian J; Owen, Lauren","year":2025,"journal":"American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists, 82(9), e426-e430","doi":"10.1093/ajhp/zxaf008","pmid":"39862389","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"First reported cases of allodynia (skin tenderness to normal touch) associated with semaglutide/GLP-1RA use. Novel adverse effect not previously documented. Adds to evolving GLP-1 safety profile.","whyItMatters":"With millions taking semaglutide, even rare side effects must be documented. Allodynia can be debilitating and may be misdiagnosed if clinicians are not aware of this association.","specificNumbers":"","methodology":"Case series documenting previously unreported allodynia in semaglutide users.","limitations":"Case series—lowest evidence level. Cannot establish causation. Rare occurrence. Other causes of allodynia may not have been fully excluded."},{"rthcId":"RPEP-13675","title":"GHRH in diabetes and metabolism.","authors":"Steenblock, Charlotte; Bornstein, Stefan R","year":2025,"journal":"Reviews in endocrine & metabolic disorders, 26(3), 413-426","doi":"10.1007/s11154-024-09930-9","pmid":"39560873","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GHRH agonists: beta-cell regeneration, survival, insulin secretion via direct islet receptor activation. GHRH antagonists: anti-inflammatory, anti-oxidative effects relevant to diabetes complications. Both offer mechanisms distinct from existing diabetes drugs.","whyItMatters":"Current diabetes drugs eventually lose effectiveness. GHRH peptides offer fundamentally different mechanisms—potentially regenerating beta-cells rather than just compensating for their loss.","specificNumbers":"","methodology":"Narrative review of GHRH agonist and antagonist biology and their diabetes-relevant mechanisms.","limitations":"Mostly preclinical evidence. Clinical translation of GHRH peptides for diabetes not yet attempted. Growth hormone effects may complicate systemic use."},{"rthcId":"RPEP-13676","title":"Semaglutide and the pathogenesis of progressive neurodegenerative disease: the central role of mitochondria.","authors":"Stefano, George B; Büttiker, Pascal; Weissenberger, Simon; Raboch, Jiri; Anders, Martin","year":2025,"journal":"Frontiers in neuroendocrinology, 79, 101217","doi":"10.1016/j.yfrne.2025.101217","pmid":"41047006","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Mitochondrial dysfunction: central to both metabolic and neurodegenerative disease. Semaglutide: improves mitochondrial function. Proposed unifying mechanism: mitochondrial rescue explains neuroprotection across Parkinson's, Alzheimer's, and other conditions.","whyItMatters":"Understanding WHY semaglutide appears neuroprotective is crucial for optimizing its use in neurological diseases. Mitochondrial rescue as the mechanism suggests dose and timing may need to be optimized for brain versus metabolic effects.","specificNumbers":"","methodology":"Narrative review proposing mitochondrial function as the mechanistic bridge between semaglutide's metabolic and neuroprotective effects.","limitations":"Hypothesis-proposing review. Mechanistic link between GLP-1R activation and mitochondrial improvement not fully defined. Brain penetration of semaglutide limited."},{"rthcId":"RPEP-13677","title":"Efficacy and Safety of GLP-1 and Dual GIP/GLP-1 Receptor Agonists in Idiopathic Intracranial Hypertension: A Systematic Review and Meta-Analysis.","authors":"Stefanou, Maria-Ioanna; Chatziralli, Irini; Lambadiari, Vaia; Mengel, Annerose; Foska, Aikaterini; Chondrogianni, Maria; Bakola, Eleni; Tsalouchidou, Panagiota-Eleni; Mitsikostas, Dimos D; Siasos, Gerasimos; Ziemann, Ulf; Tsivgoulis, Georgios","year":2025,"journal":"European journal of neurology, 32(9), e70358","doi":"10.1111/ene.70358","pmid":"40937960","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1/GIP agonists significantly reduced: intracranial pressure, headache burden (frequency + severity), BMI. Evidence of both weight-dependent and weight-independent mechanisms. CSF secretion reduction demonstrated.","whyItMatters":"IIH causes devastating vision loss and chronic headaches, with limited effective treatments. GLP-1 drugs could become a disease-modifying therapy addressing both the underlying obesity and the intracranial pressure directly.","specificNumbers":"","methodology":"Systematic review and meta-analysis of GLP-1 and GIP/GLP-1 RA studies in IIH.","limitations":"Limited number of studies. Heterogeneous study designs. Small patient numbers. Long-term efficacy unknown."},{"rthcId":"RPEP-13678","title":"Enzymatic absorption promoters for non-invasive peptide delivery.","authors":"Steiger, Marilena Bohley; Steinauer, Angela; Gao, Daniel; Cerrejon, David Klein; Krupke, Hanna; Heussi, Miguel; Merkl, Padryk; Klipp, Alexander; Burger, Michael; Martin-Olmos, Cristina; Leroux, Jean-Christophe","year":2025,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 382, 113675","doi":"10.1016/j.jconrel.2025.113675","pmid":"40164434","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Three categories of enzymatic promoters: protease inhibitors (prevent degradation), mucolytic enzymes (clear mucus barrier), tight junction openers (enable paracellular transport). Applicable to oral, nasal, pulmonary peptide delivery.","whyItMatters":"Most peptide drugs (insulin, GLP-1 agonists, growth hormones) require injection—limiting patient compliance and access. Enabling oral delivery would transform treatment for millions of patients with diabetes, obesity, and hormonal conditions.","specificNumbers":"","methodology":"Narrative review of enzymatic strategies for improving non-invasive peptide drug absorption.","limitations":"Review of emerging technology. Most strategies are preclinical. Safety of chronic mucosal permeability enhancement needs evaluation. Bioavailability often remains low."},{"rthcId":"RPEP-13679","title":"Multicentric Matched-Pair Analysis of Long-Term Hematotoxicity of Peptide Receptor Radionuclide Therapy in Patients Postsplenectomy.","authors":"Steinhelfer, Lisa; Jungmann, Friederike; Endroes, Lukas; Lanzafame, Helena; Hermann, Ken; Pfob, Christian H; Lapa, Constantin; Hartrampf, Philipp E; Dörrler, Anna-Lena; Buck, Andreas K; Götze, Katharina; Wenzel, Patrick; Geisler, Fabian; Walter, Robert; Haneder, Eva; Lohöfer, Fabian; Haller, Bernhard; Braren, Rickmer; Eiber, Matthias","year":2025,"journal":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 66(12), 1934-1940","doi":"10.2967/jnumed.125.270190","pmid":"41043998","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Leukocyte decline at 24 months: 12.8% (splenectomized) vs 47.2% (non-splenectomized), p significant. Lower leukopenia rates. Better lymphocyte/neutrophil preservation. 34 matched pairs. 2009-2022.","whyItMatters":"Hematologic toxicity limits PRRT cycles. Knowing splenectomized patients tolerate PRRT better enables clinicians to consider more aggressive treatment for these patients, who often have pancreatic NETs with poorer prognosis.","specificNumbers":"","methodology":"Multicenter retrospective matched-pair analysis. 68 patients (34 splenectomized matched to 34 non-splenectomized). Blood counts at baseline, 12, and 24 months. CTCAE grading. Bonferroni correction.","limitations":"Retrospective. 34 pairs is moderate. Matching may not capture all confounders. Splenic accumulation mechanism assumed but not directly measured."},{"rthcId":"RPEP-13680","title":"Fibrosis markers as prognostic markers of decline in kidney function in patients with neuroendocrine neoplasms undergoing peptide receptor radionuclide therapy.","authors":"Stemann Lau, Tobias; Bossen, Lars; Rasmussen, Daniel Guldager Kring; Genovese, Federica; Karsdal, Morten; Arveschoug, Anne Kirstine; Grønbæk, Henning; Dam, Gitte","year":2025,"journal":"Frontiers in endocrinology, 16, 1495369","doi":"10.3389/fendo.2025.1495369","pmid":"40655397","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"uC3M significantly lower in kidney-decline patients after 1st treatment (74 vs 135 ng/mg) and 3 months post-EOT (56 vs 118 ng/mg). 43% (6/14) had >25% kidney function decline. Median follow-up 12 months. Other fibrosis markers (PRO-C3, PRO-C6) not significantly different.","whyItMatters":"Kidney damage from PRRT is irreversible. A urine biomarker that predicts who will lose kidney function could enable protective interventions or dose adjustments before permanent damage occurs.","specificNumbers":"","methodology":"Prospective cohort of 14 NEN patients undergoing PRRT. Serum and urine fibrosis markers (PRO-C3, PRO-C6, C3M) measured before and after each treatment. Kidney function tests through 24 months post-EOT. Linear mixed models.","limitations":"Very small sample (14 patients). Exploratory analysis. Overall mixed model only marginally significant (p=0.078). Needs larger validation study."},{"rthcId":"RPEP-13681","title":"Modern antidiabetic therapy by sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 receptor agonists, and dipeptidyl peptidase 4 inhibitors against cardiovascular diseases.","authors":"Steven, Sebastian; Kuntic, Marin; Münzel, Thomas; Daiber, Andreas","year":2025,"journal":"Pharmacological reviews, 77(5), 100082","doi":"10.1016/j.pharmr.2025.100082","pmid":"40803202","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"All three drug classes: antioxidant, anti-inflammatory, endothelial protective. GLP-1RAs + SGLT2i: reduce CV mortality, protect against ischemia/reperfusion, slow HF progression. Mechanisms: oxidative stress reduction, inflammation suppression, NO signaling improvement, epigenetic/microbiotic pathway modulation.","whyItMatters":"Understanding WHY these drugs protect the heart helps optimize their use—benefits are not just from glucose control but from direct organ protection through anti-inflammatory and antioxidant mechanisms.","specificNumbers":"","methodology":"Comprehensive narrative review comparing mechanisms of cardiovascular protection across DPP-4i, GLP-1RA, and SGLT2i drug classes.","limitations":"Narrative review. Mechanistic evidence largely from preclinical studies. Direct comparisons between classes limited. Not all patients may derive equal cardiovascular benefit."},{"rthcId":"RPEP-13682","title":"Thymosin β4 stabilizes hypoxia induced brain microvascular endothelial cell dysfunction through S1PR1 dependent mechanisms.","authors":"Stewart, William G; Hejl, Christina D; Guleria, Rakeshwar S; Gupta, Sudhiranjan","year":2025,"journal":"Scientific reports, 15(1), 45764","doi":"10.1038/s41598-025-28435-2","pmid":"41326489","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tβ4 reversed hypoxia-induced tight junction damage in hBMVECs. Restored tight junction proteins. Reduced endothelial permeability. S1PR1 identified as the target mechanism. S1PR1 inhibition abolished Tβ4 protection.","whyItMatters":"BBB breakdown after brain injury causes secondary brain damage. Tβ4 could become a therapeutic peptide to prevent this, especially since no current drugs effectively protect the BBB.","specificNumbers":"","methodology":"In vitro study using hBMVECs under hypoxia. Tβ4 pretreatment. Gene expression analysis of tight junction proteins. Permeability assays. Tight junction dynamics. S1PR1 inhibition experiments.","limitations":"In vitro only. Single cell type. Pretreatment design—clinical use would require post-injury administration. Human BBB involves multiple cell types not modeled. S1PR1 mechanism needs in vivo confirmation."},{"rthcId":"RPEP-13683","title":"Association of semaglutide use with depressive symptoms and suicidal behavior in a patient with type 2 diabetes: A case report.","authors":"Stojkovska, Anisija; Rus Prelog, Polona; Kokalj Palandacic, Anja","year":2025,"journal":"The Journal of international medical research, 53(7), 3000605251349393","doi":"10.1177/03000605251349393","pmid":"40652323","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Late 70s male; no psychiatric history; T2DM. Developed restlessness + depressive mood ~1 month after semaglutide start. First suicide attempt (impulsive). Symptoms improved after semaglutide discontinuation.","whyItMatters":"While umbrella reviews find no population-level suicidal risk signal, individual case reports like this highlight that some patients may be vulnerable. The absence of psychiatric history makes this case particularly notable.","specificNumbers":"","methodology":"Single case report with temporal association.","limitations":"Single case. Cannot prove causation. Temporal association could be coincidental. Other factors may have contributed. Very rare event."},{"rthcId":"RPEP-13684","title":"Tackling suboptimal clinical response after metabolic bariatric surgery: Impact of tirzepatide on weight loss and body composition.","authors":"Stoll, Fabian; Kantowski, Tobias; Laaser, Jonas; Kloiber, Ulrike; Plitzko, Gabriel; Mann, Oliver; Aberle, Jens; Lautenbach, Anne","year":2025,"journal":"Obesity research & clinical practice, 19(1), 63-69","doi":"10.1016/j.orcp.2025.02.004","pmid":"39952885","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"TWL: 12.0% ± 3.4% (p<0.001). ≥5% loss: 100%; ≥10%: 76.5%; ≥15%: 23.5%. Significant reductions: BMI, waist circumference, body fat %, HbA1c. Similar across sexes and surgery types. Predictors: baseline BMI nadir, weight regain, body composition, CRP.","whyItMatters":"Post-bariatric weight regain affects 20-30% of patients and has limited treatment options. Tirzepatide achieving 100% ≥5% weight loss in this challenging population demonstrates exceptional efficacy.","specificNumbers":"","methodology":"Retrospective analysis of 21 post-bariatric non-T2DM patients with IWL or WR treated with tirzepatide for 6 months. Body composition by BIA. Metabolic and inflammatory markers.","limitations":"Small sample (n=21). Retrospective. No control group. 6-month follow-up. Non-diabetic patients only."},{"rthcId":"RPEP-13685","title":"Semaglutide Improves Myocardial Perfusion and Performance in a Large Animal Model of Coronary Artery Disease.","authors":"Stone, Christopher; Harris, Dwight D; Broadwin, Mark; Kanuparthy, Meghamsh; Nho, Ju-Woo; Yalamanchili, Keertana; Hamze, Jad; Abid, M Ruhul; Sellke, Frank W","year":2025,"journal":"Arteriosclerosis, thrombosis, and vascular biology, 45(2), 285-297","doi":"10.1161/ATVBAHA.124.321850","pmid":"39665144","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Improved LVEF at rest and during pacing (both p significant). Increased myocardial perfusion to ischemic segments (p=0.008). Increased capillary density (p=0.008). AMPK pathway activation (p=0.005). eNOS upregulation (p=0.014). 8 treated vs 9 control pigs.","whyItMatters":"This is the first study proving oral semaglutide directly improves cardiac function and blood flow in ischemic hearts, independent of metabolic effects. This supports using semaglutide specifically for coronary artery disease, not just as a diabetes/obesity drug.","specificNumbers":"","methodology":"Yorkshire swine (n=17): ameroid constrictor on LCx → chronic ischemia. Oral semaglutide (1.5→3 mg) for 5 weeks vs no drug. Microsphere perfusion, pressure-volume loops, immunoblotting, immunohistochemistry.","limitations":"Pig model (though highly translational). Small sample (17). Short treatment (5 weeks). Oral semaglutide doses may not match human exposure. No long-term outcomes."},{"rthcId":"RPEP-13686","title":"Increased infection risk in patients on preventive CGRP-targeting therapies- a meta-analysis and clinical effect assessment.","authors":"Straburzyński, Marcin; Kopyt, Daria; Marschollek, Karol; Błaszczyk, Bartłomiej; Kuca-Warnawin, Ewa; Kurowska, Weronika; Misiak, Błażej; Peng, Kuan-Po; Waliszewska-Prosół, Marta; May, Arne","year":2025,"journal":"The journal of headache and pain, 26(1), 88","doi":"10.1186/s10194-025-02040-0","pmid":"40281424","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Overall: RR 1.08 (1.01-1.14, p=0.016), NNH=287. Galcanezumab: RR 1.13 (p=0.024), NNH=77. Eptinezumab higher doses: RR 1.23 (p=0.015), NNH=24. Fremanezumab: fewest SAEs. Erenumab: most SAEs. 37 RCTs, 22,518 patients.","whyItMatters":"CGRP plays a role in immune defense. This is the first comprehensive analysis confirming a small but real infection risk increase with CGRP-blocking therapies—important for immunocompromised patients or public health contexts.","specificNumbers":"","methodology":"Systematic review per PRISMA-Harms. 37 placebo-controlled RCTs. Fixed/random effects NMA. Risk of bias and sensitivity analyses. Infectious SAE search in DB and OLE studies.","limitations":"Infection definitions varied across trials. Short trial durations may underestimate long-term risk. NNH is relatively high (287). Individual drug differences may reflect dosing rather than molecular differences."},{"rthcId":"RPEP-13687","title":"A dominant, pan-DR binding epitope of Der p 1 in house dust mite allergy induces tolerance in HLA-DR4 transgenic mice.","authors":"Streeter, Heather B; Lucas, Lora G; West, Robert M; Krishna, Mamidipudi T; Wraith, David C","year":2025,"journal":"Frontiers in immunology, 16, 1569283","doi":"10.3389/fimmu.2025.1569283","pmid":"40292297","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Pan-DR binding peptide D identified from in silico prediction. Elevated response in 25 HDM-sensitized patients. Minimal epitope D121B: verified as antigen-processing independent (apitope). Induced tolerance against Der p 1 in HLA-DR4 transgenic mice in vivo.","whyItMatters":"Current allergen immunotherapy carries anaphylaxis risk and requires years of treatment. Tolerogenic peptides could provide safer, more targeted allergy treatment by directly silencing pathogenic T-cells without activating mast cells.","specificNumbers":"","methodology":"In silico epitope prediction. Synthetic peptide panel (A-E). PBMC screening in 45 participants (25 HDM-sensitized, 10 atopic controls, 10 healthy). Minimal epitope mapping. Apitope validation and tolerance induction in HLA-DR4 transgenic mice.","limitations":"Preclinical (transgenic mice). Single HLA-DR allele tested. Translation to human immune diversity needs evaluation. Clinical efficacy in patients not yet demonstrated."},{"rthcId":"RPEP-13688","title":"Obesity in Hidradenitis Suppurativa: Are GLP-1 Receptor Agonists the New Frontier?","authors":"Strong, Jennifer; Driscoll, Marcia S","year":2025,"journal":"American journal of clinical dermatology, 26(2), 175-182","doi":"10.1007/s40257-024-00911-x","pmid":"39690371","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Liraglutide and semaglutide: improved HS disease severity and quality of life in early studies. Mechanisms: weight loss (reduced mechanical stress) + anti-inflammatory effects. Obesity increases HS prevalence and severity.","whyItMatters":"HS is severely debilitating with limited treatment options. GLP-1 drugs could address the underlying obesity driver while providing direct anti-inflammatory benefits—a dual-action approach currently unavailable.","specificNumbers":"","methodology":"Narrative review of GLP-1RA evidence in hidradenitis suppurativa.","limitations":"Review of early/limited studies. No RCTs for HS specifically. Small sample sizes. Cannot separate weight loss from anti-inflammatory contributions."},{"rthcId":"RPEP-13689","title":"Perioperative Glucagon-like Peptide-1 Receptor Agonist Use Is Associated With Lower Pseudoarthrosis Rates Following Long-Segment Spinal Deformity Correction: A Propensity-Matched Analysis.","authors":"Stump, Kyle; Kelleher, Sean; Hannah, Theodore C; Patel, Neal; Kanuparthi, Prasad; Vij, Rohan; Kim, Bong-Soo","year":2025,"journal":"Global spine journal, 21925682251396965","doi":"10.1177/21925682251396965","pmid":"41217855","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Pseudoarthrosis reduction: 6m RR 0.677 (p=0.028), 1y RR 0.708 (p=0.036), 2y RR 0.671 (p=0.010), 3y RR 0.714 (p=0.024). Readmission RR 0.863 (p=0.012). Sepsis RR 0.485 (p=0.002). No increased complications.","whyItMatters":"Pseudoarthrosis (non-fusion) affects 5-35% of spinal fusion patients, often requiring revision surgery. GLP-1 drugs potentially improving bone healing could benefit millions of spine surgery patients.","specificNumbers":"","methodology":"Retrospective propensity-matched 1:1 cohort. Adults with ≥7-level posterior spinal instrumentation (2010-2024). GLP-1 RA within 6 months of surgery vs no use.","limitations":"Retrospective. Propensity matching cannot eliminate all confounders. GLP-1 users may differ in important unmeasured ways (health consciousness, diabetes management). Bone healing mechanism speculative."},{"rthcId":"RPEP-13690","title":"Ectopic GHRH production: revisiting a rare cause of acromegaly.","authors":"Stumpf, Matheo A M; Santana, Nathalie Oliveira; Machado, Marcio Carlos; Duarte, Felipe H; Glezer, Andrea; Raverot, Gérald; Raverot, Véronique; Jallad, Raquel S","year":2025,"journal":"Reviews in endocrine & metabolic disorders, 26(4), 593-602","doi":"10.1007/s11154-025-09961-w","pmid":"40169474","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Ectopic GHRH from NETs: clinically indistinguishable from pituitary acromegaly. Clues: pituitary hyperplasia (not adenoma), elevated serum GHRH, extra-pituitary tumor. Treatment: tumor resection + somatostatin analogs. Risk: persistent hyperplasia/adenoma from prolonged GHRH exposure. MEN1 testing recommended.","whyItMatters":"Misdiagnosing ectopic GHRH acromegaly as pituitary adenoma leads to unnecessary pituitary surgery. Recognizing the correct diagnosis enables targeted NET treatment and avoids surgical complications.","specificNumbers":"","methodology":"Narrative review of ectopic GHRH acromegaly diagnosis, management, and long-term follow-up.","limitations":"Review of a rare condition—limited case numbers. Diagnostic algorithms not standardized. Long-term outcomes data sparse."},{"rthcId":"RPEP-13691","title":"Activation of peripheral NOP receptors reduces periorbital mechanical allodynia evoked by CGRP in mice.","authors":"Sturaro, Chiara; Pola, Pietro; Argentieri, Michela; Frezza, Alessia; Marini, Matilde; De Logu, Francesco; Albanese, Valentina; Soukupova, Marie; Malfacini, Davide; Zaveri, Nurulain T; Nassini, Romina; Jensen, Dane D; Geppetti, Pierangelo; Calò, Girolamo; Ruzza, Chiara","year":2025,"journal":"British journal of pharmacology","doi":"10.1111/bph.70162","pmid":"40817710","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"UFP-112 (peripheral) = AT-403 (brain-penetrant) for reducing CGRP-evoked PMA. N/OFQ internalized NOP and recruited Gαi at membrane + endosomes. N/OFQ attenuated CGRP-induced cAMP in human Schwann cells. NOP knockout: no baseline difference in CGRP sensitivity.","whyItMatters":"Peripheral-only NOP agonists could provide migraine relief without CNS side effects. The identification of Schwann cells as the cellular target bridges neuropeptide pharmacology with peripheral nerve biology.","specificNumbers":"","methodology":"CGRP-induced PMA in wild-type, NOP-/-, and CD-1 mice. NOP agonists (AT-403, UFP-112). HEK293 NOP signaling studies. Human Schwann cell cAMP assays.","limitations":"Mouse model. Schwann cell as cellular site needs in vivo confirmation. UFP-112 pharmacokinetics in humans unknown. Single pain model tested."},{"rthcId":"RPEP-13692","title":"Effects of intra-articular applied rat BMSCs expressing alpha-calcitonin gene-related peptide or substance P on osteoarthritis pathogenesis in a murine surgical osteoarthritis model.","authors":"Stöckl, Sabine; Taheri, Shahed; Maier, Verena; Asid, Amir; Toelge, Martina; Clausen-Schaumann, Hauke; Schilling, Arndt; Grässel, Susanne","year":2025,"journal":"Stem cell research & therapy, 16(1), 117","doi":"10.1186/s13287-025-04155-2","pmid":"40045368","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"αCGRP-BMSCs: reduced lateral cartilage OARSI scores, improved mobility, bell-shaped inflammation curve, increased adiponectin. SP-BMSCs: earlier osteophytes (8 weeks), more subchondral bone changes, decreased mobility, rising pain/inflammation markers. Plain BMSCs: general cartilage/bone benefit.","whyItMatters":"This provides direct evidence that neuropeptides have opposite effects on joints—CGRP is protective while substance P is destructive. This has major implications for both OA treatment (CGRP agonists) and pain management (SP antagonists).","specificNumbers":"","methodology":"DMM surgical OA in mice. I.a. injection of rBMSCs transduced with lacZ (control), SP, or αCGRP. Assessment at 2, 8, 16 weeks: motion analysis, OARSI scoring, AFM, nano-CT, serum markers.","limitations":"Xenogeneic transplant (rat cells in mice). Small group sizes likely. Transduced cells may not replicate physiological peptide release. Medial cartilage (main OA site) showed less treatment response than lateral."},{"rthcId":"RPEP-13693","title":"Effects of Liraglutide on Leptin Promoter Methylation in Ovarian Granulosa Cells of Obese Polycystic Ovary Syndrome Patients.","authors":"Su, Lina; Hao, Xiaoxia; Lu, Wenhong","year":2025,"journal":"The Tohoku journal of experimental medicine, 266(3), 199-207","doi":"10.1620/tjem.2025.J009","pmid":"39880646","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Obese PCOS: elevated BMI, insulin, glucose, HOMA-IR, testosterone, estradiol; reduced LEP promoter methylation. Liraglutide: ↑LEP promoter methylation → ↓leptin levels → altered sex hormones. Weight/fat loss observed. 135 obese + 72 non-obese PCOS patients.","whyItMatters":"Leptin dysregulation impairs ovarian function in PCOS. Discovering that liraglutide epigenetically modulates leptin in ovarian cells provides a mechanistic link between GLP-1 therapy and improved reproductive outcomes.","specificNumbers":"","methodology":"Prospective observational study. 207 PCOS patients (135 obese, 72 non-obese) undergoing IVF (March 2020-Jan 2022). Obese patients received liraglutide. LEP promoter methylation in granulosa cells. Serum/follicular fluid leptin. Hormonal profiling.","limitations":"Observational. No randomized control for liraglutide. Cannot separate weight loss from direct epigenetic effects. Methylation measured at a population level. IVF outcomes not reported."},{"rthcId":"RPEP-13694","title":"The pathogenic role of calcitonin gene-related peptide and predictors of new-onset migraine and long-term outcomes after transcatheter atrial septal defect closure.","authors":"Su, Tzu-Hsuan; Wang, Jou-Kou; Kuo, Ping-Hung; Chang, Shu-Hui; Chiou, Lih-Chu; Lee, Wang-Tso; Fan, Pi-Chuan","year":2025,"journal":"Headache, 65(5), 791-801","doi":"10.1111/head.14885","pmid":"39660641","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"New-onset migraine: 20.3% (43/212). CGRP elevated post-closure in migraine patients: 47.9 vs 38.0 pg/mL (p=0.023). NPY: no change. Predictors: young age (aOR 0.98), large ASD (aOR 1.07), residual shunting (aOR 2.78). Unremitting migraine: 48% at 14 years.","whyItMatters":"This reveals that CGRP—the target of modern migraine drugs—may be causally involved in post-cardiac-procedure migraine. Anti-CGRP therapy could potentially prevent or treat this common procedure complication.","specificNumbers":"","methodology":"Prospective cohort of 212 patients (2001-2013). Pre/post-closure echocardiography, CGRP and NPY levels. NOM assessment. 14-year telephone follow-up (2022).","limitations":"Prospective but observational. CGRP measured in plasma (may not reflect brain levels). No intervention tested. Telephone follow-up for long-term migraine status. NPY not elevated—only CGRP implicated."},{"rthcId":"RPEP-13695","title":"Suprachiasmatic Nucleus Vasoactive Intestinal Peptide Neurons Mediate Light-induced Transient Forgetting.","authors":"Su, Xiaoya; Tang, Yikai; Zhong, Yi; Liu, Yunlong","year":2025,"journal":"Neuroscience bulletin, 41(11), 2025-2035","doi":"10.1007/s12264-025-01456-7","pmid":"40670769","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Bright light activated SCN VIP neurons (c-Fos + Ca²+ imaging). Light selectively impaired trace fear memory. Optogenetic activation replicated the effect. Chemogenetic inhibition prevented it. SCN→PVT VIP circuit identified as essential pathway. Novel non-circadian role for VIP neurons.","whyItMatters":"This reveals a new brain function for VIP neurons—controlling memory accessibility based on light. Understanding this mechanism could explain why bright environments impair certain types of recall and could inform treatments for memory disorders.","specificNumbers":"","methodology":"c-Fos immunostaining, fiber photometry Ca²+ recording, optogenetic activation, chemogenetic (DREADD) inhibition of SCN VIP neurons. Trace fear conditioning behavioral paradigm. Circuit mapping (SCN→PVT).","limitations":"Mouse study. Trace fear memory is one specific memory type. Transient forgetting mechanism in humans may differ. VIP role in other memory types not tested."},{"rthcId":"RPEP-13696","title":"Comparison of Sodium-Glucose Cotransporter 2 Inhibitors Versus Glucagon-Like Peptide-1 Receptor Agonists and Risks of Osteoarthritis and Arthroplasty in Patients With Type 2 Diabetes Mellitus: A Propensity Score-Matched Cohorts Retrospective Study.","authors":"Su, Yu-Chi; Hsieh, Pei-Chun; Lai, Edward Chia-Cheng; Lin, Yu-Ching","year":2025,"journal":"Diabetes/metabolism research and reviews, 41(5), e70051","doi":"10.1002/dmrr.70051","pmid":"40478380","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"SGLT2i vs GLP-1RA: OA HR 0.951 (95% CI 0.916-0.988); joint replacement HR 0.703 (95% CI 0.550-0.898). 37,676 matched per group. Mean age 59.5. TriNetX platform (131M patients).","whyItMatters":"Osteoarthritis affects millions and has no disease-modifying drug. If SGLT2 inhibitors truly reduce OA risk, they could become the first pharmacological agents with joint-protective properties.","specificNumbers":"","methodology":"Propensity score-matched retrospective cohort from TriNetX Global Collaborative Network (131M patients, 109 organizations). 51,177 SGLT2i and 52,977 GLP-1RA users matched to 37,676 per group.","limitations":"Retrospective observational. GLP-1 users may have higher BMI (more OA risk). Joint replacement as outcome may reflect referral patterns. Cannot determine mechanism."},{"rthcId":"RPEP-13697","title":"An oral liraglutide nanomicelle formulation conferring reduced insulin-resistance and long-term hypoglycemic and lipid metabolic benefits.","authors":"Subedi, Laxman; Bamjan, Arjun Dhwoj; Phuyal, Susmita; Shim, Jung-Hyun; Cho, Seung-Sik; Seo, Jong Bae; Chang, Kwan-Young; Byun, Youngro; Kweon, Seho; Park, Jin Woo","year":2025,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 378, 637-655","doi":"10.1016/j.jconrel.2024.12.039","pmid":"39709071","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"LDD-NM: 75.9 nm particles; permeability +1347%; oral bioavailability 5.14% vs 1.11% (4.63x). 12-week oral: superior to SC for HOMA-IR, HbA1c, BAT activation, anti-inflammatory genes, lipid metabolism. Absorption: clathrin endocytosis + macropinocytosis + ASBT pathway.","whyItMatters":"Oral GLP-1 delivery is the holy grail of peptide drug development. This formulation not only achieves meaningful oral bioavailability but shows the oral route may produce different (potentially superior) metabolic effects than injection.","specificNumbers":"","methodology":"Nanomicelle synthesis (electrostatic complexation + DDM surfactant). Caco-2/HT29-MTX-E12 permeability. Rat oral bioavailability. 12-week oral treatment in diabetic rats. Metabolic, adipose tissue, and gene expression analysis.","limitations":"Rat study. Oral bioavailability still low (5.14%). Daily dosing of 20 mg/kg is high. Manufacturing scalability unclear. Human translation needed."},{"rthcId":"RPEP-13698","title":"First report on a case series of Patulous Eustachian tube following GLP-1 receptor agonist-induced weight loss.","authors":"Sudhoff, Holger","year":2025,"journal":"European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery, 282(12), 6533-6538","doi":"10.1007/s00405-025-09604-5","pmid":"40721956","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"7 patients (5F, 2M; age 28-56); bilateral PET in 5. 4-10 months GLP-1 therapy; 8.2-18.7% weight loss. Symptoms: autophony (7/7), aural fullness (6/7), hearing breathing (5/7). Treatment: 6/7 needed VOX-Implant injections; 1/7 conservative improvement.","whyItMatters":"As millions lose weight on GLP-1 drugs, this previously unrecognized otologic side effect could become common. Clinicians need to recognize and refer these patients early.","specificNumbers":"","methodology":"Retrospective case series (June 2024-June 2025). Otolaryngology clinic. Diagnosis: otoscopy, DVT, tympanometry, tubomanometry.","limitations":"Small case series. No control comparison. Cannot prove causation vs coincidence. PET diagnosis can be subjective."},{"rthcId":"RPEP-13699","title":"Maturity-Onset Diabetes of the Young (MODY) With HNF1B p.Glu105Lys Mutation Achieving Significant Insulin Reduction on Tirzepatide: A Case Report.","authors":"Sue, Mihiro; Watanabe, Mayu; Inoue, Ayumi; Katayama, Akihiro; Teshigawara, Sanae; Matsushita, Yuichi; Takeda, Masaya; Iseda, Izumi; Eguchi, Jun; Hida, Kazuyuki","year":2025,"journal":"Clinical case reports, 13(2), e70173","doi":"10.1002/ccr3.70173","pmid":"39902194","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"C-peptide: 0.36→1.09 ng/mL (3x increase). Insulin: 88→4 units/day. Glimepiride discontinued. HNF1B p.Glu105Lys MODY. 26-year-old, 15-year diabetes duration.","whyItMatters":"MODY is characterized by impaired insulin secretion, and this case shows tirzepatide can dramatically restore it. This could change management of MODY subtypes that retain some beta-cell function.","specificNumbers":"","methodology":"Single case report of tirzepatide in MODY with HNF1B mutation.","limitations":"Single case. Cannot generalize to all MODY subtypes. HNF1B MODY is rare. Long-term durability unknown."},{"rthcId":"RPEP-13700","title":"Comparative Effects of Dulaglutide and Semaglutide on Renal Function Decline and Proteinuria Reduction in Diabetic Patients: A Retrospective Cohort Study.","authors":"Sue, Yuh-Mou; Lu, De-En; Chang, Te-I; Chen, Chun-You; Chen, Cheng-Hsien; Hsu, Shih-Chang; Chu, Yen-Ling; Huang, Nai-Jen; Chen, Tso-Hsiao; Lin, Feng-Yen; Shih, Chun-Ming; Huang, Po-Hsun; Hsieh, Hui-Ling; Liu, Chung-Te","year":2025,"journal":"Journal of clinical medicine, 14(12)","doi":"10.3390/jcm14124287","pmid":"40566032","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"eGFR: similar decline in both groups (NS). UACR: dulaglutide significantly higher increases vs semaglutide (p significant). Semaglutide superior for UACR in: higher BMI, higher HbA1c, older patients. 747 semaglutide vs 268 dulaglutide, 12 months.","whyItMatters":"Proteinuria is a major driver of kidney disease progression. Demonstrating that semaglutide reduces it more than dulaglutide helps clinicians choose the best GLP-1 drug for diabetic kidney disease.","specificNumbers":"","methodology":"Retrospective cohort at Wanfang Hospital, Taipei (Jan 2022-Sep 2024). 1,015 patients. eGFR and UACR at 12 months. Subgroup analyses.","limitations":"Retrospective. Single center in Taiwan. Groups not perfectly balanced at baseline. Specific UACR values not detailed in abstract. 12-month follow-up may not capture long-term differences."},{"rthcId":"RPEP-13701","title":"Differences between therapeutic mechanisms of resmetirom and semaglutide against MASH in western diet-fed MC4R-knockout mice.","authors":"Sugawara, Takumi; Hitaka, Kosuke; Matsumoto, Mitsuharu; Nakamura, Sayuri; Kobayashi, Ryosuke; Kandori, Hitoshi; Nio, Yasunori","year":2025,"journal":"Scientific reports, 15(1), 41068","doi":"10.1038/s41598-025-24927-3","pmid":"41266634","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Both: improved liver hydroxyproline, total fat. Resmetirom: ↑O2 consumption, significantly improved steatosis. Semaglutide: ↓energy expenditure, ↓lean mass, significantly reduced fibrosis. Different mechanisms confirmed. First head-to-head comparison.","whyItMatters":"With both drugs available for MASH, understanding their different mechanisms enables rational combination strategies. Resmetirom targets fat through metabolism; semaglutide targets fibrosis through weight/inflammation—together they could address all MASH components.","specificNumbers":"","methodology":"MC4R-KO mice on western diet. 6 weeks disease induction + 7 weeks drug treatment. Resmetirom vs semaglutide vs control. Body composition, metabolic cages, histopathology (steatosis + fibrosis scores).","limitations":"Mouse model (MC4R-KO). Short treatment (7 weeks). Cannot directly translate doses to humans. Lean mass loss in mice may differ from humans."},{"rthcId":"RPEP-13702","title":"Once-Weekly Semaglutide Is Associated With Improvement in Vascular Endothelial Function in Patients With Type 2 Diabetes Mellitus: A Retrospective Observational Study.","authors":"Sugiyama, Seigo; Yoshida, Akira; Kurinami, Noboru; Hieshima, Kunio; Jinnouchi, Katsunori; Suzuki, Tomoko; Miyamoto, Fumio; Kajiwara, Keizo; Jinnouchi, Hideaki","year":2025,"journal":"Cureus, 17(12), e99998","doi":"10.7759/cureus.99998","pmid":"41583249","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"RHI: 1.62±0.19 → 2.04±0.60 (p<0.01). BW, HbA1c, LDL-cho also improved (all p<0.01). hsCRP trended down (NS). No correlation between metabolic changes and RHI improvement. 24 patients, mean age 55, 83% male.","whyItMatters":"Endothelial dysfunction is the earliest step in atherosclerosis. Demonstrating that semaglutide directly improves endothelial function—independent of metabolic improvements—reveals a direct vascular protective mechanism.","specificNumbers":"","methodology":"Retrospective observational study at Jinnouchi Hospital (Japan). 24 T2DM patients initiated on once-weekly SC semaglutide since 2021. RHI by EndoPAT. Clinical parameters before and after treatment.","limitations":"Small sample (24). Retrospective. No control group. Japanese population. RHI has measurement variability. Follow-up duration not specified."},{"rthcId":"RPEP-13703","title":"Trans-kingdom conservation of mechanism between bacterial actifensin and eukaryotic defensins.","authors":"Sugrue, Ivan; Ade, Carolin; O'Connor, Paula M; Daniel, Jan-Martin; Innocenti, Paolo; Kirsch, Nico; Martin, Nathaniel I; Weindl, Günther; Hill, Colin; Schneider, Tanja; Paul Ross, R","year":2025,"journal":"npj antimicrobials and resistance, 3(1), 66","doi":"10.1038/s44259-025-00135-x","pmid":"40695989","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Actifensin binds lipid II (Kd=30 nM) and lipid I (Kd=24 nM). No membrane disruption. Cell death via cell wall weakening. No hemolysis or cytotoxicity up to 128 µg/ml. No immunogenicity (LDH, TLR signaling). GXGCP motif conserved trans-kingdom.","whyItMatters":"Finding that bacterial and eukaryotic defensins share the same killing mechanism validates lipid II as a universal antimicrobial target. Actifensin's safety profile (non-toxic, non-immunogenic) makes it an attractive antibiotic candidate.","specificNumbers":"","methodology":"Lipid II/I binding assays. DiSC3(5) fluorescence (membrane integrity). Liposome disruption. Phase contrast microscopy. Hemolysis. HepG2 cytotoxicity. PBMC immunogenicity (LDH, TLR signaling). Structural motif analysis.","limitations":"In vitro characterization only. Gram-positive spectrum may limit clinical applications. In vivo efficacy not tested. Production scalability unknown."},{"rthcId":"RPEP-13704","title":"Semaglutide in MASLD Patients: Improved Survival and Liver Outcomes.","authors":"Suki, Mohamad; Amer, Johnny; Milgrom, Yael; Massarwa, Muhammad; Hazou, Wadi; Tiram, Yariv; Perzon, Ofer; Sharif, Yousra; Sackran, Joseph; Alon, Revital; Lourie, Nachum Emil Eliezer; Raz, Itamar; Imam, Ashraf; Khalaileh, Abed; Safadi, Rifaat","year":2025,"journal":"Pharmaceuticals (Basel, Switzerland), 18(7)","doi":"10.3390/ph18071075","pmid":"40732362","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"38,224 matched patients (19,112 each). BMI reduction ~1 point. Significantly improved: 1-year survival, cardiovascular parameters, liver-related outcomes, advanced liver disease markers, synthetic function. 34 matching variables. TriNetX platform.","whyItMatters":"This is the largest real-world MASLD semaglutide study to date. Showing improved survival and reduced advanced liver disease in nearly 20,000 treated patients provides compelling evidence for semaglutide as a disease-modifying MASLD therapy.","specificNumbers":"","methodology":"Propensity score-matched cohort from TriNetX (135M patients, 112 healthcare organizations). 34-variable matching. MASLD by ICD9. Outcomes: survival, biochemical, metabolic, cardiovascular, liver-specific.","limitations":"Observational. Short follow-up (1 year). Semaglutide group had higher baseline BMI (potential selection bias). TriNetX data quality varies across sites."},{"rthcId":"RPEP-13705","title":"When the Transition Goes Wrong: A Rare Case of Diabetic Ketoalkalosis After Transitioning to Tirzepatide in Insulin-dependent Type 2 Diabetes.","authors":"Sultan, Waleed; Spencer, Jeanne","year":2025,"journal":"Cureus, 17(6), e87031","doi":"10.7759/cureus.87031","pmid":"40746803","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Diabetic ketoalkalosis (simultaneous ketosis + alkalosis). 57-year-old, insulin-dependent T2DM. Switched to tirzepatide. Mechanism: insulin deficiency (ketosis) + vomiting (alkalosis). Resolved with fluids, electrolytes, insulin.","whyItMatters":"As more insulin-dependent diabetics transition to GLP-1/GIP drugs, mixed acid-base disorders like ketoalkalosis may increase. Recognizing this rare but dangerous complication is essential for safe transition protocols.","specificNumbers":"","methodology":"Single case report with metabolic analysis.","limitations":"Single case. Very rare complication. Other contributing factors possible. Cannot establish incidence."},{"rthcId":"RPEP-13706","title":"A Probable Case of Tirzepatide-Induced Acute Pancreatitis.","authors":"Sumaruth, Yovan; Gopal, Rudramun; Chater, Faris; Dhawan, Saurav; Wild, Tamzin","year":2025,"journal":"Cureus, 17(6), e85291","doi":"10.7759/cureus.85291","pmid":"40612832","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Age 32; 5 weeks tirzepatide (2.5→5 mg); lipase 11,645 U/L (100x upper normal). Elevated transaminases, ALP, bilirubin. CT: acute interstitial pancreatitis. MRCP: gallstones but no obstruction. Resolved after cessation + supportive care.","whyItMatters":"With tirzepatide prescriptions surging, clinicians must recognize pancreatitis as a potential side effect—even in young patients without traditional risk factors. The gallstone confound makes this diagnostic challenge realistic.","specificNumbers":"","methodology":"Detailed case report with imaging (CT, MRCP), laboratory data, and temporal analysis.","limitations":"Single case. Gallstones present (confounding). Cannot definitively exclude gallstone pancreatitis despite no obstruction. Causation assumed based on temporal correlation."},{"rthcId":"RPEP-13707","title":"Cardiovascular effects of tirzepatide.","authors":"Sumithran, Priya; Russell, Anthony W; Zoungas, Sophia","year":2025,"journal":"The Journal of endocrinology, 264(2)","doi":"10.1530/JOE-24-0259","pmid":"39751188","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Unprecedented: HbA1c, weight, BP, lipid improvements vs placebo and GLP-1RAs. CV safety confirmed. CV benefit: unknown (pending SURPASS-CVOT and other trials). GIP receptor CV contribution: not established.","whyItMatters":"Tirzepatide is being prescribed to millions but lacks the CV outcome data that made semaglutide a first-line cardiovascular drug. Understanding this evidence gap is critical for prescribing decisions.","specificNumbers":"","methodology":"Narrative review of tirzepatide cardiovascular trial data and ongoing outcome studies.","limitations":"Review of available data with major outcome trials still ongoing. Cannot answer the key CV benefit question yet."},{"rthcId":"RPEP-13708","title":"Efficacy of collagen peptide supplementation on bone and muscle health: a meta-analysis.","authors":"Sun, Chongxiao; Yang, Ao; Teng, Fei; Xia, Yayi","year":2025,"journal":"Frontiers in nutrition, 12, 1646090","doi":"10.3389/fnut.2025.1646090","pmid":"41049371","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BMD: significant increase femoral neck + spine (I²=80.1%). Bone turnover: SMD 0.40-0.58 (I²=0%). Muscle function: SMD 0.60 (I²=0%). Collagen + vitamin D + calcium: synergistic SMDs 0.40-0.56.","whyItMatters":"Osteoporosis and sarcopenia are major causes of disability in aging. Collagen peptide supplementation offers a safe, accessible adjunct to standard treatments that improves both bone and muscle health.","specificNumbers":"","methodology":"Systematic review and meta-analysis of RCTs evaluating collagen peptide supplementation on BMD, bone turnover, and muscle function. Standardized mean differences with 95% CI.","limitations":"High heterogeneity for BMD outcomes (I²=80.1%). Varied collagen types and doses across trials. Duration of studies varied. Cannot determine optimal dose or type."},{"rthcId":"RPEP-13709","title":"Exploring the Effect and Mechanism of Liraglutide in Treating Depression Based on Network Pharmacology and Experimental Analysis.","authors":"Sun, Jiangjin; Fu, Xiying; Liu, Yaqi; Wang, Tian; Zhao, Xing; Cui, Ranji; Yang, Wei","year":2025,"journal":"Journal of cellular and molecular medicine, 29(11), e70630","doi":"10.1111/jcmm.70630","pmid":"40461955","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Liraglutide: reduced depressive behaviors in chronic stress mice. Mechanism: PI3K/AKT → Nrf2 activation → HMGB1 downregulation → reduced microglial inflammation + oxidative stress. In vitro: BV2-HT22 co-culture confirmed neuroprotection. Novel pathway for antidepressant mechanism.","whyItMatters":"Depression affects 300 million people with many non-responders to current treatments. Discovering a novel anti-inflammatory mechanism for liraglutide's antidepressant effects could open new therapeutic approaches, especially for inflammation-driven depression.","specificNumbers":"","methodology":"Network pharmacology target prediction. In vivo chronic stress depression mouse model. In vitro BV2 microglia/HT22 neuron co-culture. Western blot, behavioral testing, inflammatory markers.","limitations":"Mouse model. Network pharmacology predictions need broader validation. Single GLP-1 drug tested. Chronic stress model is one of several depression models. Translation to human depression uncertain."},{"rthcId":"RPEP-13710","title":"The global clinical trial landscape for non-alcoholic fatty liver disease (NAFLD): current status and future prospects.","authors":"Sun, Jing; Shi, Run; Zhu, Xinrui; Liu, Yi; Shi, Wenjie; Zhao, Tianyu; Wang, Xuanbin; Zhou, Xiqiao","year":2025,"journal":"International journal of surgery (London, England), 111(9), 6430-6434","doi":"10.1097/JS9.0000000000002654","pmid":"40474833","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"2,242 trials analyzed. GLP-1RAs most frequently tested agents. US: 488 trials, China: 384. GLP-1R downregulated in NAFLD liver tissue. Further downregulation in NASH. Semaglutide binding confirmed by molecular docking.","whyItMatters":"Understanding that GLP-1R expression decreases as liver disease advances raises important questions about drug efficacy in severe NASH and may guide timing of treatment intervention.","specificNumbers":"","methodology":"Trialtrove database analysis (2,242 trials). Molecular docking of semaglutide-GLP-1R. Transcriptome analysis of NAFLD datasets (healthy vs NAFLD vs NASH). Geographic and phase distribution mapping.","limitations":"Trial landscape analysis is descriptive. Transcriptomic analysis shows association not causation. GLP-1R downregulation mechanism unclear. Does not assess clinical trial outcomes."},{"rthcId":"RPEP-13711","title":"Effects of semaglutide on metabolism and gut microbiota in high-fat diet-induced obese mice.","authors":"Sun, Luyan; Shang, Bingqing; Lv, Suyuan; Liu, Guolong; Wu, Qiu; Geng, Yue","year":2025,"journal":"Frontiers in pharmacology, 16, 1562896","doi":"10.3389/fphar.2025.1562896","pmid":"40552153","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide: ↓weight, fat, FBG, insulin, HOMA-IR. Modulated liver/adipose metabolic genes + hypothalamic appetite genes. Reshaped gut microbiota. FMT transferred benefits to recipients. Weight rebounded 4 weeks after stopping. Amino acid and pyrimidine metabolism affected.","whyItMatters":"This proves semaglutide's benefits are partly mediated by gut bacteria—not just appetite suppression. The FMT experiment is particularly significant: it shows the metabolic improvements are transmissible through the microbiome.","specificNumbers":"","methodology":"C57BL/6J mice: ND, HFD, HFD+semaglutide (100 μg/kg). FMT from semaglutide mice to pseudo-germ-free recipients. Serum metabolomics. 16S rRNA gut microbiota. Gene expression (liver, adipose, hypothalamus).","limitations":"Mouse study. FMT from drug-treated mice may not replicate human microbiome effects. Weight rebound after cessation may limit long-term benefit of microbiome changes alone."},{"rthcId":"RPEP-13712","title":"Anticancer Bioactive Peptides from Plants: Sources, Action Mechanisms, and Potential Superiority to Conventional Chemotherapy.","authors":"Sun, Mao-Cheng; Yu, Shi-Qi; Zhao, Changhui; Lee, Chi-Ching; Suttikhana, Itthanan; Ashaolu, Tolulope Joshua","year":2025,"journal":"Probiotics and antimicrobial proteins","doi":"10.1007/s12602-025-10781-2","pmid":"40974531","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Sources: legumes, cereals, medicinal plants. Mechanisms: apoptosis (mitochondrial), cell cycle arrest, anti-angiogenesis (VEGF), membrane disruption, metastasis inhibition. Advantages vs chemo: tumor selectivity, reduced toxicity, less resistance. Challenges: stability, delivery, production.","whyItMatters":"Cancer treatment is limited by chemotherapy toxicity and resistance. Plant-derived peptides offer a natural, multi-mechanism approach that may overcome both limitations while causing fewer side effects.","specificNumbers":"","methodology":"Comprehensive narrative review of plant-derived anticancer peptide sources, mechanisms, therapeutic potential, and translational challenges.","limitations":"Review of primarily preclinical data. No PDACPs are currently approved for cancer. Stability and delivery remain significant challenges. In vivo efficacy data limited."},{"rthcId":"RPEP-13713","title":"Intranasal Absorption Enhancement of Antidiabetic Therapeuticals by the Functional Peptide Segment of Latroeggtoxin-VI.","authors":"Sun, Minglu; Yin, Panfeng; Chen, Si; Wang, Xianchun","year":2025,"journal":"Molecular pharmaceutics, 22(7), 4046-4055","doi":"10.1021/acs.molpharmaceut.5c00293","pmid":"40515721","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"FPS-GLP: concentration-dependent cell entry in vitro. Intranasal FPS-GLP > GLP-1 analogue alone for hypoglycemia. Intranasal FPS-Ins ≈ intramuscular FPS-Ins for blood sugar reduction. 17-residue C-terminal FPS as transmembrane delivery vector.","whyItMatters":"Injectable administration is the main barrier to peptide drug compliance. A spider-derived nasal delivery system could enable non-invasive delivery of GLP-1 drugs and insulin, dramatically improving patient convenience.","specificNumbers":"","methodology":"Solid phase synthesis (FPS-GLP), heterologous expression (FPS-Ins). A549 cell entry assays (Western blot). Mouse intranasal administration. Blood glucose monitoring.","limitations":"Proof of concept only. Mouse study. Specific bioavailability numbers not stated. Long-term safety of repeated intranasal FPS use unknown. Scale-up challenges."},{"rthcId":"RPEP-13714","title":"Neuroprotective effects of lixisenatide against propagation of α-synuclein pathology in Parkinson's disease.","authors":"Sun, Shangqi; Huang, Liqin; Jiang, Gege; Xie, Guanfeng; Li, Xiaoyi; Wang, Xiufeng; Guo, Hongxiu; Wang, Cailin; Zheng, Siyi; Li, Gang; Xiong, Jing","year":2025,"journal":"Neural regeneration research","doi":"10.4103/NRR.NRR-D-24-00941","pmid":"40145958","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Lixisenatide: ↓α-synuclein phosphorylation, aggregation, propagation. ↓Mitochondrial dysfunction and apoptosis in cells. 20-week mouse treatment: improved motor function, protected dopaminergic neurons. Mechanism: inhibited LAG3-mediated neuron-to-neuron α-synuclein seeding.","whyItMatters":"This identifies the specific mechanism—LAG3-mediated seeding inhibition—by which GLP-1 drugs could slow PD progression. This goes beyond symptom management to disease modification.","specificNumbers":"","methodology":"In vitro: α-synuclein PFF-treated cells. In vivo: stereotactic PFF injection into mouse striatum + 20-week lixisenatide treatment. α-Synuclein pathology, motor assessment, dopaminergic neuron counts, LAG3 expression.","limitations":"Mouse model with PFF injection. Lixisenatide (short-acting) may differ from long-acting GLP-1 drugs. 20 weeks may not capture long-term PD progression. LAG3 mechanism needs human validation."},{"rthcId":"RPEP-13715","title":"Tirzepatide Synergizes with Leptin on Weight Loss and Restoring Metabolic Homeostasis in Diet-induced Obesity Model.","authors":"Sun, Xun; Yin, Yuexi; Song, Min; Droz, Brian A; Lin, Yanzhu; Beaty, Kristen N; Zhou, Baohua; Roh, Hyun Cheol; Wilson, Jonathan M; Cain, Paul F; Samms, Ricardo J; Sheets, Patrick L; Ai, Minrong; Ren, Hongxia","year":2025,"journal":"bioRxiv : the preprint server for biology","doi":"10.64898/2025.12.18.695152","pmid":"41509321","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Clinical: baseline leptin correlated with tirzepatide weight loss. Mouse: TZP+Lep synergistic weight loss, ↑hepatic insulin sensitivity, ↑BAT thermogenesis, ↓food intake + ↑energy expenditure under thermoneutrality. Mechanism: sensitized POMC and GLP-1R neurons to leptin. Increased POMC firing by reducing inhibitory inputs.","whyItMatters":"Leptin resistance is a fundamental obstacle in obesity. If tirzepatide can restore leptin sensitivity, combining the two could achieve greater weight loss than either alone—and this study proves it.","specificNumbers":"","methodology":"Clinical trial leptin correlation analysis. DIO mouse model. Tirzepatide + leptin combination. Metabolic profiling under thermoneutrality. Hypothalamic neuron electrophysiology. POMC and GLP-1R neuron leptin signaling.","limitations":"Mouse study. Clinical correlation is observational. Combination therapy not tested clinically. Optimal dosing ratios unknown. Long-term safety of leptin combination unclear."},{"rthcId":"RPEP-13716","title":"Characterization and Role of Glucagon-Like Peptide 1 Receptor in the Lacrimal Gland: Novel Insights into Diabetic Dry Eye Pathogenesis.","authors":"Sun, Yan; Zhang, Yue; Shi, Fan; Li, Ye; Wang, Congyao; Yu, Fenfen; Chen, Tingting; Dong, Xia; Xu, Yuqi; Zhao, Yu; Wan, Pengxia","year":2025,"journal":"The American journal of pathology, 195(4), 797-810","doi":"10.1016/j.ajpath.2024.12.003","pmid":"39725294","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"First: GLP-1R identified in lacrimal gland. GLP-1R downregulated in diabetes. Diabetes: lacrimal inflammation, fibrosis, atrophy, ↓tear secretion. Topical liraglutide: ↓inflammation, ↓fibrosis, ↑autophagy, ↑tear production. RNA-seq: inflammatory pathways enriched.","whyItMatters":"Diabetic dry eye affects millions and current treatments only address symptoms (artificial tears). GLP-1 eye drops could be the first disease-modifying treatment by protecting the lacrimal gland itself.","specificNumbers":"","methodology":"Type 1 diabetic mouse model. Phenol red thread tear test. RNA-seq of lacrimal gland tissue. GLP-1R expression analysis. Histology (inflammation, fibrosis). Topical liraglutide eye drops. Autophagy markers.","limitations":"Type 1 diabetes mouse model. Topical formulation details not specified. Long-term safety of GLP-1 eye drops unknown. Translation to human diabetic dry eye needs validation."},{"rthcId":"RPEP-13717","title":"Diagnostic Evaluation of an Increased Risk of Developing Small Intestinal Bacterial Overgrowth Associated with Glucagon-like Peptide-1 (GLP-1) Receptor Agonists and Dual GLP-1/GIP Receptor Agonists: A Global Retrospective Multicenter Cohort Analysis.","authors":"Sun, Yan; Veccia, Donovan; Liu, Benjamin Douglas Xun; Tse, William; Fass, Ronnie; Song, Gengqing","year":2025,"journal":"Diagnostics (Basel, Switzerland), 15(17)","doi":"10.3390/diagnostics15172264","pmid":"40941750","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Short-term SIBO: HR 2.14 (1.13-4.07, p=0.049). Incidence: 0.177 vs 0.083 per 1,000 patient-years. Long-term: HR 2.02 (0.98-4.12, NS), but KM divergence p=0.017. 216,173 per cohort. TriNetX database.","whyItMatters":"SIBO causes bloating, malabsorption, and nutritional deficiencies—symptoms that overlap with GLP-1 drug side effects. Clinicians need to consider SIBO as a possible diagnosis in GLP-1 users with persistent GI symptoms.","specificNumbers":"","methodology":"Retrospective cohort from TriNetX global database. Adult T2DM patients on GLP-1RA/GIP vs other second-line agents. 1:1 propensity matching (216,173 per group). Short and long-term SIBO analysis.","limitations":"Retrospective. SIBO diagnosis depends on breath testing availability. Very low absolute incidence. Cannot determine which GLP-1 drugs drive the risk. Excluded gastroparesis patients may have biased results."},{"rthcId":"RPEP-13718","title":"Thymosin β4 released by mast cells under stress conditions impairs intestinal epithelial barrier via IL22RA1/JAK1/STAT3 signaling in irritable bowel syndrome.","authors":"Sun, Yue-Shan; Bai, Xiao-Qin; Sun, Kai-Di; Li, Jiao; Liu, Lei; Chen, Yuan-Yuan; Zeng, Zhao-Yu; Wang, Qiong; Guo, Yuan-Biao","year":2025,"journal":"World journal of gastroenterology, 31(42), 111706","doi":"10.3748/wjg.v31.i42.111706","pmid":"41278163","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"High Tβ4 in IBS mucus and mast cells. Tβ4: ↓tight junctions, ↓IL22RA1/Reg3γ, ↑MLCK. Tβ4-/- rats: stress-resistant. CRH receptor 1: triggers Tβ4 release (not degranulation). Mechanism: IL22RA1/JAK1/STAT3 pathway inhibition.","whyItMatters":"IBS affects 10-15% of the global population with limited understanding of its pathogenesis. Identifying Tβ4 as a specific mediator linking stress, mast cells, and barrier dysfunction provides a targetable mechanism for this common condition.","specificNumbers":"","methodology":"IBS patient samples. Tβ4-/- rats, Kit w-sh/w-sh (MC-deficient) mice. In vivo stress models. In vitro barrier assays. CRH/Tβ4 release mechanisms. Western blot, immunostaining.","limitations":"Animal models may not fully replicate human IBS. Tβ4 measurement in IBS patients was correlative. Therapeutic Tβ4 targeting not yet tested."},{"rthcId":"RPEP-13719","title":"Serendipitous Hinge Modulation Hypothetically Reprograms Caerin 1.1-LC Antibacterial Mechanism and Gram-Negative Selectivity.","authors":"Sun, Zhengze; Zhao, Ruixin; Zhang, Yueao; Ma, Xiaonan; Jiang, Yangyang; Wang, Tao; Chen, Xiaoling; Ma, Chengbang; Chen, Tianbao; Shaw, Chris; Zhou, Mei; Wang, Lei","year":2025,"journal":"Pharmaceutics, 17(11)","doi":"10.3390/pharmaceutics17111500","pmid":"41304836","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"D-amino acid hinge modification: 8x ↑Gram-negative activity, ↓hemolysis, 56x ↑therapeutic index (0.47→26.6). Mechanism switch: membrane disruption → cell-penetrating mode (depolarization + ATP disruption). In vivo: effective in larval infection models. LPS neutralization confirmed.","whyItMatters":"A single structural modification producing 56-fold therapeutic improvement demonstrates that peptide engineering can overcome the toxicity-efficacy trade-off that limits AMP clinical development.","specificNumbers":"","methodology":"Peptide isolation from L. caerulea skin secretion. D-isomer analogues. MIC assays. Hemolysis. Membrane permeability assays. ATP measurement. Membrane potential. In vivo larval infection models. LPS neutralization.","limitations":"D-amino acids may affect in vivo stability differently. Larval model is not equivalent to mammalian infection. Manufacturing of D-amino acid peptides is more expensive. Gram-positive activity not detailed."},{"rthcId":"RPEP-13720","title":"Glucagon-like Peptide-1 Receptor Agonists: Exciting Avenues Beyond Weight Loss.","authors":"Sundararaman, Lalitha; Gouda, Divakara; Kumar, Anil; Sundararaman, Sumithra; Goudra, Basavana","year":2025,"journal":"Journal of clinical medicine, 14(6)","doi":"10.3390/jcm14061978","pmid":"40142784","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Established: glycemic control, weight loss, CV event reduction, hypertension, dyslipidemia. Emerging: NASH, Alzheimer's, cancer (certain types), infertility, associative learning. Pipeline: insulin icodec (weekly), IcoSema (weekly insulin+semaglutide).","whyItMatters":"Clinicians prescribing GLP-1 drugs need to understand their full benefit profile to maximize patient care. This comprehensive overview covers both established and emerging applications.","specificNumbers":"","methodology":"Narrative review of GLP-1RA applications beyond diabetes across multiple therapeutic areas.","limitations":"Review of varying evidence quality. Some applications based on preliminary data. Not all emerging indications will be validated."},{"rthcId":"RPEP-13721","title":"Mimotopes of calcitonin gene-related peptide (CGRP) screened from Fv-antibody library: antagonists to CGRP receptor.","authors":"Sung, Jeong Soo; Bae, Hyung Eun; Kang, Min-Jung; Jose, Joachim; Lee, Misu; Chu, Min Kyung; Pyun, Jae-Chul","year":2025,"journal":"International journal of biological macromolecules, 334(Pt 2), 149080","doi":"10.1016/j.ijbiomac.2025.149080","pmid":"41253226","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"VH-format mimotopes: highest CGRP receptor binding and antagonist activity. Blocked CGRP-induced cAMP and Ca2+ in SK-N-MC cells. Docking: mimotopes bind at CLR interface preventing CGRP binding. Three formats compared: VH > Fv > CDR3 peptides.","whyItMatters":"Current anti-CGRP therapies use expensive monoclonal antibodies. Smaller peptide-based CGRP antagonists could be cheaper to produce and potentially suitable for non-injectable delivery routes.","specificNumbers":"","methodology":"Fv-antibody library screening. CDR3 peptides, Fv-antibodies, VH heavy chains prepared. Binding assays. cAMP and Ca2+ assays in SK-N-MC cells. Computer-aided docking simulation.","limitations":"In vitro only. Single cell line. Binding affinity values not quantified in abstract. In vivo anti-migraine efficacy not tested. Pharmacokinetics unknown."},{"rthcId":"RPEP-13722","title":"One-step ultra-rapid immunoassay of calcitonin gene-related peptide for migraine diagnosis.","authors":"Sung, Jeong Soo; Jung, Jaeyong; Kwon, Soonil; Bae, Hyung Eun; Kang, Min-Jung; Jose, Joachim; Lee, Misu; Cho, Soomi; Chu, Min Kyung; Pyun, Jae-Chul","year":2025,"journal":"Biosensors & bioelectronics, 270, 116980","doi":"10.1016/j.bios.2024.116980","pmid":"39608279","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Analysis time: 32 minutes. LOD: 8.8 pg/mL (fremanezumab mimotope F1), 9.4 pg/mL (galcanezumab mimotope G7). LOQ: 125.9 and 84.7 pg/mL. Successfully distinguished 57 migraine patients from 18 controls. Consistent with conventional CGRP assay.","whyItMatters":"CGRP measurement has been impractical clinically because the peptide degrades too quickly. A 32-minute test makes CGRP measurement feasible for point-of-care migraine diagnosis and treatment monitoring.","specificNumbers":"","methodology":"Mimotope peptide synthesis from Fv-antibody library (4 clones × 2 mAbs). 15-residue peptides. KD estimation. Docking simulations. One-step immunoassay development. Clinical validation (57 migraine + 18 control).","limitations":"Small clinical sample (57+18). Single-center. LOQ values may limit quantification at low concentrations. Needs multi-center validation. Pre-analytical handling still critical."},{"rthcId":"RPEP-13723","title":"Redefining Cystic Fibrosis-Related Diabetes Management With Tirzepatide: A Case Report.","authors":"Suresh Babu, Yashwanth; Jayagopal, Vijay","year":2025,"journal":"Cureus, 17(11), e97448","doi":"10.7759/cureus.97448","pmid":"41439084","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"First CFRD case on tirzepatide. Improved: HbA1c, glucose control, weight, blood pressure. 3-month follow-up. No major adverse effects. Long-standing CFRD on basal-bolus insulin. 51-year-old woman.","whyItMatters":"CFRD is the most common CF comorbidity, and CFTR modulators are changing its metabolic landscape. Tirzepatide addresses both glucose control and the emerging cardiometabolic syndrome in modern CF patients.","specificNumbers":"","methodology":"Single case report of tirzepatide in CFRD.","limitations":"Single case. Short follow-up (3 months). Cannot generalize to all CFRD patients. CF-specific safety concerns (malabsorption, underweight risk) not fully addressed."},{"rthcId":"RPEP-13724","title":"Blinded by the drug? A vigilyze signal linking semaglutide to NAION.","authors":"Suresh, Jaishree; Vivekanandan, Kalaiselvan","year":2025,"journal":"International ophthalmology, 45(1), 398","doi":"10.1007/s10792-025-03760-7","pmid":"41026313","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"91 NAION cases among 73,636 semaglutide reports. 97.8% serious. Denmark: 38 cases (41.8%). Age 45-74: 54.9%. Male predominance. Co-reported: visual impairment 13.2%, blindness 9.9%, optic atrophy 4.4%, visual field defect 5.5%.","whyItMatters":"With 91 globally reported cases and nearly all classified as serious, this confirms NAION as a rare but significant safety concern with semaglutide. The call for label updates reflects the severity—NAION causes irreversible vision loss.","specificNumbers":"","methodology":"Retrospective post-market analysis of VigiBase (WHO global ICSR database) through June 2025. MedDRA terminology mapping. Descriptive analysis of NAION cases.","limitations":"ICSR data: spontaneous reporting with inherent biases. Cannot calculate incidence (no denominator). Denmark overrepresented (may reflect reporting culture). Causation not established."},{"rthcId":"RPEP-13725","title":"Antagonizing NK-1R modulates pain perception following corneal injury.","authors":"Surico, Pier Luigi; Naderi, Amirreza; Singh, Rohan Bir; Kahale, Francesca; Farsi, Yeganeh; Lee, Seokjoo; Musayeva, Aytan; Chen, Yihe; Dana, Reza","year":2025,"journal":"Experimental eye research, 251, 110230","doi":"10.1016/j.exer.2025.110230","pmid":"39761841","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"NK-1R antagonist (L-733,060): ↓corneal SP, ↑nerve fiber density at 21 days, ↓trigeminal activation markers (ATF3, GFAP, cFos, TRPV1, TRPM8), ↓pain responses (eye-wiping test + palpebral ratio). 21-day topical treatment.","whyItMatters":"Corneal pain after injury or surgery is debilitating. NK-1R antagonists could simultaneously reduce pain and promote nerve healing—unlike current analgesics that only address symptoms.","specificNumbers":"","methodology":"C57BL/6 mice corneal injury model. L-733,060 or vehicle topical 2x daily for 21 days. ELISA (SP), β-Tubulin III staining (nerve density), qPCR (trigeminal markers), pain behavioral tests (EWT, PR).","limitations":"Mouse model. Topical delivery of L-733,060 (not a clinically available eye drop). 21-day study may not capture long-term effects. Pain assessment in mice has limitations."},{"rthcId":"RPEP-13726","title":"Bioactive peptides PIISVYWK and FSVVPSPK improve glucose homeostasis by targeting DPP-IV and glucose transport in type 2 diabetic mice.","authors":"Suryaningtyas, Indyaswan T; Jung, Won-Kyo; Lee, Sei-Jung; Je, Jae-Young","year":2025,"journal":"International immunopharmacology, 158, 114844","doi":"10.1016/j.intimp.2025.114844","pmid":"40359889","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"P1 and P2: inhibited α-glucosidase and DPP-IV in Caco-2 cells. ↑GLP-1 levels. ↓NF-κB, IL-6, TNF-α, IL-1β. ↑SOD, GPx, CAT. Preserved β-cell function. ↑insulin, regulated glucagon. 1-10 mg/kg vs metformin 200 mg/kg in HFD/STZ mice.","whyItMatters":"Marine-derived peptides that simultaneously target multiple diabetes mechanisms could become natural therapeutic alternatives or adjuncts to existing drugs, with potentially fewer side effects.","specificNumbers":"","methodology":"In vitro: Caco-2 cell DPP-IV, α-glucosidase, glucose uptake, SGLT-1/GLUT2 expression. In vivo: HFD/STZ diabetic mice, P1/P2 (1 or 10 mg/kg) or metformin (200 mg/kg) for 4 weeks.","limitations":"Mouse study. Bioavailability of oral peptides in humans uncertain. Short treatment (4 weeks). Dose comparison to metformin may not be directly translatable."},{"rthcId":"RPEP-13727","title":"Human cathelicidin peptide LL-37 induces endothelial-to-mesenchymal transition.","authors":"Suzuki, Kaori; Ohkuma, Mari; Nagaoka, Isao","year":2025,"journal":"Bioscience, biotechnology, and biochemistry, 89(10), 1464-1473","doi":"10.1093/bbb/zbaf112","pmid":"40690262","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"LL-37: ↓EC markers, ↑mesenchymal markers. ↓Vascular network formation. ↑Cell migration. Mechanism: Akt + NF-κB activation. Blocked by Akt and NF-κB inhibitors. LL-37 localized in atherosclerotic plaques.","whyItMatters":"EndMT contributes significantly to atherosclerotic plaque formation. Finding that LL-37—an innate immune peptide—drives this process links antimicrobial defense to cardiovascular disease pathogenesis.","specificNumbers":"","methodology":"In vitro: HUVEC treated with LL-37. EC/mesenchymal marker expression. Network formation assay. Migration assay. Akt and NF-κB pathway inhibitor studies.","limitations":"In vitro HUVEC model. LL-37 concentrations may not reflect in vivo plaque levels. EndMT is one of many atherosclerosis mechanisms. Causation in human atherosclerosis not established."},{"rthcId":"RPEP-13728","title":"The effect of calcitonin gene-related peptide monoclonal antibodies on restless legs syndrome in patients with migraine.","authors":"Suzuki, Keisuke; Suzuki, Shiho; Fujita, Hiroaki; Kobayashi, Saro; Shioda, Mukuto; Hida, Ryotaro; Hirata, Koichi","year":2025,"journal":"The journal of headache and pain, 26(1), 36","doi":"10.1186/s10194-025-01976-7","pmid":"39972460","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"≥50% MMD reduction: 53-67% across months. IRLS: -8.8 points (1 month), -11.6 points (3 months). MIDAS: 25.1→19.7 (p=0.005). CSI: 36.3→29.1 (p=0.001). PGIC RLS improvement: 73.3%. RLS improvement even in migraine non-responders: 66.6%.","whyItMatters":"RLS affects 5-10% of the population with limited treatment options. Finding that anti-CGRP drugs improve RLS—independently of migraine—suggests CGRP plays a role in RLS and could lead to a new treatment approach.","specificNumbers":"","methodology":"Retrospective study of 15 migraine+RLS patients on CGRP mAbs (2 erenumab, 3 galcanezumab, 10 fremanezumab). IRLS, MIDAS, CSI, PGIC at 1-3 months.","limitations":"Very small (n=15). Retrospective. No control group. Predominantly female (93%). Three different CGRP mAbs used. Placebo effect cannot be excluded."},{"rthcId":"RPEP-13729","title":"Perceptions and Attitudes Toward Oral Semaglutide Among Japanese Physicians and Individuals with Type 2 Diabetes: A Web-Based Survey.","authors":"Suzuki, Ryo; Chand, Krishant; Taguchi, Yuu","year":2025,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 16(7), 1479-1495","doi":"10.1007/s13300-025-01739-2","pmid":"40434552","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Pre-prescribing: 17.2% expected ≥80% adherence, 56.4% resistant. Post-prescribing: 44.6% reported ≥80% adherence, 95.2% of patients missed ≤1 dose/week. Physician resistance decreased in 44.2%. 330 physicians + 412 patients surveyed.","whyItMatters":"Physician hesitation about oral semaglutide's dosing complexity has limited prescribing. This survey proves real-world adherence far exceeds expectations, potentially removing a key barrier to oral GLP-1 drug adoption.","specificNumbers":"","methodology":"Web-based survey across 330 treating physicians and 412 T2DM patients. Baseline and post-initiation perceptions of oral semaglutide adherence and dosing requirements.","limitations":"Japanese population—cultural adherence factors may differ. Web-based survey with potential selection bias. Self-reported adherence may overestimate. Oral semaglutide specific formulation requirements."},{"rthcId":"RPEP-13730","title":"β-Cell Function and Sensitivity to Incretins Before and After Roux-en-Y Gastric Bypass in Individuals With Type 2 Diabetes.","authors":"Svane, Maria S; Hindsø, Morten; Martinussen, Christoffer; Dirksen, Carsten; Jørgensen, Nils B; Hedbäck, Nora; Hartmann, Bolette; Kristiansen, Viggo B; Holst, Jens J; Bojsen-Møller, Kirstine N; Madsbad, Sten","year":2025,"journal":"Diabetes, 74(9), 1652-1663","doi":"10.2337/db24-1054","pmid":"40608389","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Post-RYGB: GLP-1 and GIP potentiated insulin during hyperglycemia. BUT relative potentiating effects reduced postoperatively: GIP (1st phase) and GLP-1 (1st + 2nd phase). Improved β-cell function driven by: ↑glucose sensitivity + exaggerated postprandial GLP-1 secretion, NOT ↑incretin sensitivity.","whyItMatters":"Understanding the mechanism behind surgical diabetes remission is essential for developing non-surgical alternatives. This study shows it's about more GLP-1 flooding the system, not better cellular responses to it.","specificNumbers":"","methodology":"Hyperglycemic clamp studies with GLP-1 and GIP infusion before and after RYGB in T2DM patients. First- and second-phase insulin secretion assessment.","limitations":"Small study (not stated in abstract). Clamp conditions are artificial. Results specific to RYGB. GIP receptor desensitization not fully explored."},{"rthcId":"RPEP-13731","title":"Human antimicrobial/host defense peptide LL-37 may prevent the spread of a local infection through multiple mechanisms: an update.","authors":"Svensson, Daniel; Nilsson, Bengt-Olof","year":2025,"journal":"Inflammation research : official journal of the European Histamine Research Society ... [et al.], 74(1), 36","doi":"10.1007/s00011-025-02005-8","pmid":"40063262","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Three mechanisms: (1) direct antimicrobial (bacteria + viruses); (2) immunomodulation (endotoxin neutralization, chemotaxis, Ca2+ signaling, both pro/anti-inflammatory); (3) cytotoxicity to infected host cells (1-10 µM). Natural concentrations: up to 300 µM in psoriasis, 1 µM in periodontitis.","whyItMatters":"Understanding LL-37's triple mechanism provides a comprehensive model for innate antimicrobial defense and informs both LL-37-based therapeutic development and understanding of when LL-37 may cause tissue damage.","specificNumbers":"","methodology":"Updated narrative review of LL-37 mechanisms in infection containment.","limitations":"Review format. In vivo concentrations may vary. The balance between beneficial and harmful LL-37 effects is context-dependent and not fully understood."},{"rthcId":"RPEP-13732","title":"Real-World Treatment Patterns Among US Patients With Type 2 Diabetes Mellitus Initiating Treatment With Once Weekly Semaglutide for Diabetes.","authors":"Swift, Caroline; Frazer, Monica; Sargent, Andrew; Leszko, Michael; Buysman, Erin; Gronroos, Noelle N; Alvarez, Sara; Dunn, Tyler J; Noone, Josh","year":2025,"journal":"Clinical therapeutics, 47(4), 277-283","doi":"10.1016/j.clinthera.2024.12.014","pmid":"39827023","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"15,588 patients. 1st LOT: semaglutide monotherapy most common. 36.5% maintained 1st LOT throughout follow-up. 2nd LOT: 42.2% included semaglutide. 3rd LOT: 45.8% included semaglutide. Persistence: 52.1% (2nd LOT) and 72.0% (3rd LOT) continued to end.","whyItMatters":"Understanding how semaglutide is actually used in clinical practice—not just how it works in trials—helps prescribers make informed treatment decisions and predict patient trajectories.","specificNumbers":"","methodology":"Retrospective claims-based study of US patients with T2DM initiating OW semaglutide (Jan 2018-Dec 2019). At least 1 year follow-up. Lines of therapy (LOT) and regimen analysis.","limitations":"Claims data cannot capture clinical reasoning. Early post-launch period (2018-2019) may not reflect current prescribing. Cannot assess glycemic outcomes. US-specific insurance landscape."},{"rthcId":"RPEP-13733","title":"Peripherally acting anti-CGRP monoclonal antibodies attenuate cortical resting-state connectivity in migraine patients.","authors":"Szabo, Edina; Bolo, Nicolas R; Borsook, David; Burstein, Rami; Ashina, Sait","year":2025,"journal":"Cephalalgia : an international journal of headache, 45(2), 3331024241313377","doi":"10.1177/03331024241313377","pmid":"39995155","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Responders (19/36): ↓functional connectivity between somatosensory/motor cortex, insula, and visual areas. Non-responders (17/36): no changes. No baseline differences between groups. 3-month galcanezumab treatment.","whyItMatters":"This provides the first neuroimaging evidence of how anti-CGRP drugs change brain function. Reducing cortical hyperexcitability explains the clinical benefit and suggests CGRP blockade initiates neural recovery beyond just pain relief.","specificNumbers":"","methodology":"Prospective resting-state fMRI study. 36 patients (high-frequency EM or CM). Pre- and post-3-month galcanezumab. ROI-to-ROI connectivity analysis. Responder (≥50% MMD reduction) vs non-responder comparison.","limitations":"Small sample (36). Cannot determine if brain changes cause or result from clinical improvement. 3-month follow-up is short. Galcanezumab only—other CGRP drugs may differ."},{"rthcId":"RPEP-13734","title":"The Mystery Actor in the Neuroendocrine Theater: Who Really Knows Obestatin? Central Focus on Hypothalamic-Pituitary Axes.","authors":"Szlis, Michał; Wójcik-Gładysz, Anna; Gajewska, Alina; Przybyl, Bartosz Jaroslaw","year":2025,"journal":"International journal of molecular sciences, 26(15)","doi":"10.3390/ijms26157395","pmid":"40806524","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Appetite: inconsistent in rodents, significant orexigenic gene changes in sheep. GH axis: no effect in rodents, ↑GHRH/somatostatin mRNA, ↑GH synthesis/secretion in sheep. Reproductive: present in Leydig/pituitary cells, modulates GnRH/LH/FSH in vitro. Species variation is major.","whyItMatters":"Despite sharing a precursor with ghrelin (one of the most studied gut peptides), obestatin remains poorly understood. Clarifying its roles could reveal new therapeutic targets in appetite, growth, and reproductive disorders.","specificNumbers":"","methodology":"Narrative review synthesizing animal studies on obestatin's central neuroendocrine effects across species (rodents and sheep).","limitations":"Review of inconsistent data across species. No clinical human studies. Obestatin's receptor remains debated. Functional relevance in humans unknown."},{"rthcId":"RPEP-13735","title":"The Involvement of the Peptidergic Systems in Breast Cancer Development.","authors":"Sánchez, Manuel L; Robinson, Prema; Italia, Zal; Hoang, Tan; Muñoz, Miguel; Coveñas, Rafael","year":2025,"journal":"Cancers, 17(22)","doi":"10.3390/cancers17223662","pmid":"41301028","tags":["neuropeptides","cancer-immunotherapy","peptide-drug-design","hormone-regulation"],"studyType":"narrative review","evidenceStrength":"low (review of field)","keyFinding":"Breast cancer cells express receptors for many peptides. Some peptides promote tumor growth (substance P, VIP, neurotensin), while others fight it (angiotensin 1-7, ghrelin). Several have dual effects depending on context.","whyItMatters":"Peptide-based strategies could offer new ways to diagnose, image, and treat breast cancer by targeting the specific peptide receptors that tumors overexpress.","specificNumbers":"Oncogenic peptides: adrenomedullin 2, endothelin, GRP, neurokinin A, NPY, neurotensin, substance P, VIP; anticancer: angiotensin 1-7, ghrelin, PYY; dual-action: GLP-1, oxytocin, kisspeptin, among others","methodology":"Comprehensive narrative review of peptidergic systems in breast cancer, covering receptor expression, signaling pathways, and therapeutic strategies.","limitations":"Narrative format. Many findings from cell lines and animal models. Clinical evidence for peptide-based breast cancer therapy is limited. Dual-action peptides complicate therapeutic strategies."},{"rthcId":"RPEP-13736","title":"Peptidergic Systems and Neuroblastoma.","authors":"Sánchez, Manuel Lisardo; Coveñas, Rafael","year":2025,"journal":"International journal of molecular sciences, 26(8)","doi":"10.3390/ijms26083464","pmid":"40331938","tags":["neuropeptides","cancer-immunotherapy","peptide-drug-design"],"studyType":"narrative review","evidenceStrength":"low (review of field)","keyFinding":"Several peptide systems are involved in neuroblastoma. Angiotensin II, NPY, neurotensin, and substance P promote tumor growth, while adrenomedullin, CRF, orexin, and urocortin have anti-cancer effects.","whyItMatters":"Neuroblastoma is a common childhood cancer with limited treatments for advanced disease. Peptide receptor targeting could provide new therapeutic approaches.","specificNumbers":"Oncogenic peptides: angiotensin II, NPY, neurotensin, substance P; anticancer: adrenomedullin, CRF, urocortin, orexin; receptor antagonists tested in cell and animal models","methodology":"Narrative review of peptidergic systems in neuroblastoma biology, covering receptor expression, signaling, and therapeutic potential.","limitations":"Narrative format. Data are fragmentary for some peptide systems. Most evidence from cell lines. No clinical trials of peptide-targeting therapies in neuroblastoma."},{"rthcId":"RPEP-13737","title":"Sex-specific alterations in emotional behavior and neurotransmitter systems in LPA1 receptor-deficient mice.","authors":"Sánchez-Marín, Laura; Jiménez-Castilla, Violeta; Flores-López, María; Navarro, Juan A; Gavito, Ana; Blanco-Calvo, Eduardo; Santín, Luis J; Pavón-Morón, Francisco J; Rodríguez de Fonseca, Fernando; Serrano, Antonia","year":2025,"journal":"Neuropharmacology, 268, 110325","doi":"10.1016/j.neuropharm.2025.110325","pmid":"39864586","tags":["neuropeptides","neuropeptide-y","hormone-regulation","brain-function"],"studyType":"preclinical study (animal model)","evidenceStrength":"low (animal study)","keyFinding":"Mice lacking the LPA1 receptor showed increased anxiety and altered stress responses, with more severe effects in females. Brain levels of neuropeptide Y and corticotropin-releasing hormone were disrupted.","whyItMatters":"This connects lipid signaling to anxiety-related neuropeptide systems and reveals sex differences that could explain why women experience more anxiety and depression than men.","specificNumbers":"maLPA1-null mice: increased anxiety in both sexes, more pronounced in females; elevated plasma LPA, reduced 2-AG; altered NPY, CRH, glutamatergic gene expression in amygdala and mPFC","methodology":"Behavioral testing (anxiety and stress-coping) in maLPA1-null and wild-type mice of both sexes. Plasma LPA, 2-AG, and corticosterone measurements. Gene expression profiling in amygdala and mPFC by RT-qPCR.","limitations":"Mouse knockout model; complete receptor loss may not reflect human variation. Behavioral tests in mice have limited translation to human anxiety. Gene expression changes do not prove functional effects."},{"rthcId":"RPEP-13738","title":"PACAP-38 in Cluster Headache: A Prospective, Case-Control Study of a Potential Treatment Target.","authors":"Søborg, Marie-Louise K; Lund, Nunu; Snoer, Agneta; Barloese, Mads; Jensen, Rigmor Højland; Petersen, Anja Sofie","year":2025,"journal":"European journal of neurology, 32(9), e70341","doi":"10.1111/ene.70341","pmid":"41002104","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"PACAP-38 elevated vs controls: overall +34.3% (p<0.0001), chronic +49.8% (p<0.0001), bout +39.5% (p<0.0001), remission +34.1% (p=0.0005). No PACAP-38/CGRP correlation (r=0.08, p=0.10). 205 patients, 101 controls.","whyItMatters":"Cluster headache is one of the most painful conditions known. While CGRP-targeting drugs help some patients, the lack of PACAP-38/CGRP correlation suggests anti-PACAP therapies could help patients who do not respond to CGRP treatments.","specificNumbers":"","methodology":"Prospective case-control study. Danish Cluster Headache Biobank. 205 CH patients (ICHD-3 criteria), 101 matched controls. Interictal plasma PACAP-38 and CGRP by validated immunoassays.","limitations":"Cross-sectional measurement—does not prove causation. Interictal measurements may not reflect attack-phase dynamics. Plasma levels may not reflect brain tissue levels. PACAP-38 elevation during remission complicates interpretation."},{"rthcId":"RPEP-13739","title":"Real-world cardiovascular effectiveness of sustained glucagon-like peptide 1 GLP-1 receptor agonist usage in type 2 diabetes.","authors":"Sørensen, Kathrine Kold; Yazdanfard, Puriya Daniel Würtz; Zareini, Bochra; Pedersen-Bjergaard, Ulrik; Kosjerina, Vanja; Andersen, Mikkel Porsborg; Munch, Anders; Ohlendorff, Johan Sebastian; Schmid, Stefanie; Lanzinger, Stefanie; Choudhary, Pratik; Gillies, Clare; Gharibzadeh, Safoora; Lind, Marcus; Tasselius, Viktor; Michelsen, Jens; Gerds, Thomas Alexander; Torp-Pedersen, Christian","year":2025,"journal":"Cardiovascular diabetology, 24(1), 385","doi":"10.1186/s12933-025-02915-1","pmid":"41053738","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"3P-MACE: -2.5% (95% CI 0.8-4.1%). CV mortality: -2.3% (1.4-3.1%). All-cause mortality: -2.5% (0.7-4.3%). HF: -0.9% (0.01-1.8%). Angina: -0.7% (0.01-1.3%). MI, stroke, revasc: NS. 6,681 GLP-1RA + 19,072 DPP-4i.","whyItMatters":"This confirms LEADER trial findings in real-world settings using rigorous causal inference methods, strengthening the evidence for GLP-1 drugs as cardiovascular protectors in everyday clinical practice.","specificNumbers":"","methodology":"Target trial emulation using Danish nationwide registries (2012-2022). LEADER-matching criteria. Longitudinal TMLE adjusting for baseline and time-varying confounding. DPP-4i as active comparator.","limitations":"Observational despite causal inference methods. Danish population may not represent all demographics. DPP-4i comparator may have own CV effects. MI and stroke individually NS."},{"rthcId":"RPEP-13740","title":"Survey among adult users of semaglutide for weight loss in Denmark: User characteristics, treatment expectations and experienced effects.","authors":"Sørensen, Malene Svoldgaard; Pottegård, Anton; Andersen, Nanna Elman; Thomsen, Reimar W; Lundby, Carina","year":2025,"journal":"Diabetes, obesity & metabolism, 27(4), 2214-2222","doi":"10.1111/dom.16222","pmid":"39905646","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"559 respondents (55% response rate). Female 78%. BMI 36 median. 70% self-initiated. 46% expected limited duration. 11% expected lifelong. 42% no duration discussion. Weight loss: 5.3% at ~5 months. Side effects: 59% (nausea 35%, constipation 29%).","whyItMatters":"The expectation gap is alarming: nearly half of users expect to stop treatment despite evidence that weight returns after discontinuation. Better patient education about long-term management is urgently needed.","specificNumbers":"","methodology":"Questionnaire-based survey across 29 Danish community pharmacies (Sep-Dec 2023). 10-day consecutive recruitment. 1,013 invited, 559 (55%) participated. Electronic questionnaire.","limitations":"Self-reported data. Danish population may not represent other countries. 55% response rate introduces selection bias. Cross-sectional snapshot at one time point."},{"rthcId":"RPEP-13741","title":"Dumping syndrome: Update on pathophysiology, diagnosis, and management.","authors":"Tack, Jan; Raymenants, Karlien; Van de Bruaene, Cedric; Scarpellini, Emidio","year":2025,"journal":"Neurogastroenterology and motility, 37(2), e14962","doi":"10.1111/nmo.14962","pmid":"39529492","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Stepwise management: diet → acarbose/viscosity → somatostatin analogues (most effective). Refractory: diazoxide, SGLT2i. Emerging: pasireotide, GLP-1RA and GLP-1 antagonists, stable glucagon. Post-bariatric hypoglycemia is late dumping only.","whyItMatters":"Dumping syndrome is underdiagnosed after the surge in bariatric surgery. This review provides a clear management algorithm and highlights peptide-based therapies (somatostatin analogues, GLP-1 drugs) as central treatments.","specificNumbers":"","methodology":"Narrative review of dumping syndrome pathophysiology, diagnosis, and current/emerging treatments.","limitations":"Many emerging therapies lack robust evidence. Somatostatin analogues are expensive. Surgical reintervention evidence is limited. \"Post-bariatric hypoglycemia\" may be overused for what is actually dumping syndrome."},{"rthcId":"RPEP-13742","title":"Oral Semaglutide Further Reduced LDL Cholesterol in a Patient with Familial Hypercholesterolemia Treated with Statins, Ezetimibe, and Evolocumab.","authors":"Tada, Hayato; Takamura, Masayuki","year":2025,"journal":"Internal medicine (Tokyo, Japan)","doi":"10.2169/internalmedicine.6198-25","pmid":"40866272","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Baseline LDL: 312 mg/dL → ~50 mg/dL on statin + ezetimibe + evolocumab. Addition of oral semaglutide: further LDL reduction. Dual benefit: diabetes control + additional LDL lowering beyond maximal therapy.","whyItMatters":"Residual cardiovascular risk persists even on maximal lipid-lowering therapy. Demonstrating that semaglutide provides additional LDL reduction positions it as a complementary agent for refractory hypercholesterolemia.","specificNumbers":"","methodology":"Single case report of oral semaglutide added to intensive lipid-lowering therapy.","limitations":"Single case. Cannot quantify the additional LDL reduction precisely from abstract. Mechanism of semaglutide LDL lowering unclear."},{"rthcId":"RPEP-13743","title":"A Stable RNA Vaccine Against the Regulatory Peptide Adrenomedullin Reduces Angiogenesis and Tumor Burden in a Subcutaneous Melanoma Model Without Inducing an Immunosuppressive Tumor Microenvironment.","authors":"Tadic, Srdan; García-Sanmartín, Josune; Narro-Íñiguez, Judit; Martínez, Alfredo","year":2025,"journal":"International journal of molecular sciences, 26(21)","doi":"10.3390/ijms262110745","pmid":"41226782","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tumor initiation delayed (p=0.005). Volume reduced (p=0.0004). Vessel area decreased (p=0.028). ↑Anti-AM IgG (p=0.033). ↑CD8+ T cells (p=0.049). No TME immunosuppression. No toxicity/weight loss. Stable at 4°C >1 month.","whyItMatters":"Targeting regulatory peptides with vaccines is a novel immunotherapy approach. Adrenomedullin vaccination achieved anti-tumor effects without the immunosuppressive side effects that plague many cancer immunotherapies.","specificNumbers":"","methodology":"C57BL/6J mice. mRNA-LNP vaccine (KLH-AM fusion). 4-dose immunization → B16-F10 melanoma injection → booster. Tumor volume, angiogenesis, immune infiltration, Ki67 proliferation analysis.","limitations":"Mouse melanoma model. Subcutaneous tumors (not metastatic in this study, though prior study tested metastatic). Single tumor type. Prophylactic rather than therapeutic setting."},{"rthcId":"RPEP-13744","title":"Molecular determinants of the selectivity and potency of α-conotoxin Vc1.1 for human nicotinic acetylcholine receptors.","authors":"Tae, Han-Shen; Hung, Andrew; Clark, Richard J; Adams, David J","year":2025,"journal":"The Journal of biological chemistry, 301(1), 108017","doi":"10.1016/j.jbc.2024.108017","pmid":"39608712","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Vc1.1: selective for hα9 (IC50=160 nM) and hα3β2 (IC50=232 nM). α9[N179A]: 20-fold ↓potency (lost H-bond with D11). β2[E86A]: 4-fold ↑potency (K104 interaction). α9[N213K]: 2-fold ↑potency. MD simulations: D5 side chain interactions altered.","whyItMatters":"α9 nAChRs mediate neuroinflammation and pain. A selective venom peptide that blocks these receptors provides a template for developing non-opioid pain treatments.","specificNumbers":"","methodology":"Two-electrode voltage clamp in Xenopus oocytes expressing human nAChR subtypes. Site-directed mutagenesis (α9, β2). Molecular dynamics simulations. IC50 determination.","limitations":"Oocyte expression may not fully replicate native receptor pharmacology. Human subtype selectivity may differ from rat. In vivo pain data only in rats. Manufacturing of disulfide-rich peptides is complex."},{"rthcId":"RPEP-13745","title":"Impact of Sleeping Habits on the Weight Loss Effect of Oral Glucagon-Like Peptide-1 Receptor Agonists Among Obese Patients: An Observational Study in Japan.","authors":"Takakura, Kazuki; Koda, Nagisa; Kinoshita, Yuji; Oh, Maki; Koyama, Muneyuki; Suka, Machi","year":2025,"journal":"Cureus, 17(7), e87823","doi":"10.7759/cureus.87823","pmid":"40655063","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Improved sleeping time or sleep quality → significantly associated with sufficient semaglutide weight loss effect. 367 Japanese adults; 69.5% female; 83.9% BMI 25-35; logistic regression analysis. Other factors assessed but sleep was significant.","whyItMatters":"Response to GLP-1 drugs varies widely. Identifying sleep as a modifiable factor that improves drug effectiveness gives clinicians a non-pharmacological lever to enhance treatment outcomes.","specificNumbers":"","methodology":"Observational study (March 2022-October 2024). 367 Japanese adults on oral semaglutide. Weight change every 3 months. Sleeping habits assessed. Logistic regression for treatment efficacy predictors.","limitations":"Observational—cannot prove causation. Self-reported sleep measures. Japanese population. Oral semaglutide specific. Confounders possible (healthier patients may both sleep better and lose more weight)."},{"rthcId":"RPEP-13746","title":"Increased autoantibodies against incretin indicate poor prognosis in patients with diabetes.","authors":"Takemoto, Minoru; Zhang, Bo-Shi; Hayashi, Aiko; Yamagata, Hiroki; Yoshida, Yoich; Koshizaka, Masaya; Onishi, Shunichiro; Yamaga, Masaya; Yoshida, Tomohiko; Hashimoto, Takahide; Ohtake, Naoki; Ishikawa, Takahiro; Takizawa, Hirotaka; Hiwasa, Takaki","year":2025,"journal":"Scientific reports, 15(1), 38313","doi":"10.1038/s41598-025-22337-z","pmid":"41184416","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"First incretin autoantibody study. GIP and GLP-1 antibodies: both significantly elevated in diabetes (p<0.01). GIP antibody positive: significantly worse 5-year prognosis (p=0.0072). GLP-1 antibody positive: trend toward worse prognosis (p=0.06). 274 patients, 109 controls, 4.9-year follow-up.","whyItMatters":"If incretin autoantibodies neutralize GIP and GLP-1, they could explain why some diabetic patients respond poorly to incretin-based therapies. This opens a completely new dimension of diabetes pathophysiology.","specificNumbers":"","methodology":"Retrospective cohort. 274 diabetic patients + 109 healthy controls. Incretin antibody titers by ALISA (amplified luminescent proximity homogeneous assay). Mean 4.9-year follow-up (max 10 years).","limitations":"Retrospective. First study—needs replication. Antibody assay methodology novel. Cannot determine if antibodies cause or result from diabetes. Prognosis definition not specified."},{"rthcId":"RPEP-13747","title":"Real world treatment patterns and unmet needs of migraine preventive treatments in Japan: JMDC claims analysis.","authors":"Takeshima, Takao; Ahmadyar, Gina; Duan, Molly; Yamazaki, Toru; Inoue, Shoko; Nishimura, Chiori","year":2025,"journal":"Current medical research and opinion, 41(8), 1559-1571","doi":"10.1080/03007995.2025.2552277","pmid":"40911496","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CGRP mAb persistence: 85.6% (3m) → 36.5% (12m). OMPM persistence: 49.7% (3m) → 21.7% (12m). Antiepileptics: highest OMPM persistence (27.0%). Switching: 22.9% OMPM, 19.7% CGRP mAb at 12m. Only 20% OMPM switchers → CGRP mAb. Comorbidities: ~50% non-migraine headache, 26-31% mental health, 29% sleep.","whyItMatters":"Low 12-month persistence across all migraine preventives—including CGRP mAbs—highlights that current treatments do not adequately meet patient needs. New approaches are needed to improve long-term migraine management.","specificNumbers":"","methodology":"Retrospective JMDC claims analysis (April 2021-January 2024). Treatment-naïve OMPM (12,750) and CGRP mAb (3,280) initiators. 60-day gap = discontinuation.","limitations":"Claims data cannot capture reasons for discontinuation. Japanese healthcare system may differ from others. 60-day gap definition may misclassify some patients. Short post-CGRP-mAb era in Japan."},{"rthcId":"RPEP-13748","title":"Short- and long-term glycemic effects of pasireotide in patients with acromegaly: a comprehensive case study with review of literature.","authors":"Taki, Yuki; Kono, Takashi; Matsuda, Tatsuma; Kozu, Ryunosuke; Fujimoto, Masanori; Sakuma, Ikki; Hashimoto, Naoko; Horiguchi, Kentaro; Higuchi, Yoshinori; Tanaka, Tomoaki","year":2025,"journal":"Endocrine journal, 72(4), 421-435","doi":"10.1507/endocrj.EJ24-0548","pmid":"39842795","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Case 1: rapid postprandial hyperglycemia → managed with dulaglutide + CGM. Case 2: long-term dose-dependent glycemia → controlled by sequential GLP-1RAs including semaglutide. CGM: essential for early detection. GLP-1RAs: effective for SSTR5-mediated hyperglycemia.","whyItMatters":"Pasireotide is an important treatment for acromegaly but hyperglycemia limits its use. Demonstrating that GLP-1 drugs effectively counteract this side effect could enable more patients to benefit from pasireotide.","specificNumbers":"","methodology":"Two-case report with literature review. CGM monitoring. Sequential GLP-1RA therapy.","limitations":"Two cases only. East Asian population. No randomized comparison. CGM not universally available."},{"rthcId":"RPEP-13749","title":"Gastrointestinal Adverse Effects of Anti-Obesity Medications in Non-Diabetic Adults: A Systematic Review.","authors":"Takrori, Ehab; Peshin, Supriya; Singal, Sakshi","year":2025,"journal":"Medicina (Kaunas, Lithuania), 61(11)","doi":"10.3390/medicina61111987","pmid":"41303824","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1RAs: nausea, vomiting, diarrhea, constipation (worst during dose escalation). Orlistat: steatorrhea, flatulence. Phentermine: ↓GI motility. Retatrutide, orforglipron: notable GI profiles. Natural products: fewer AEs but limited data. Generally mild-moderate but affect adherence.","whyItMatters":"GI side effects are the #1 reason patients stop obesity medications. Understanding the specific profile of each drug class enables better counseling and management strategies.","specificNumbers":"","methodology":"PRISMA 2020 systematic review. PubMed, Google Scholar, BMJ, Web of Science (to July 2025). 12 studies. Cochrane RoB 2 and Newcastle-Ottawa quality assessment.","limitations":"Heterogeneous study designs. Inconsistent AE reporting. Most data from clinical trials. Long-term GI outcomes unknown for newer agents."},{"rthcId":"RPEP-13750","title":"Efficacy of GLP-1 receptor agonists in patients with obesity and heart failure with preserved ejection fraction: A systematic review and meta-analysis of randomised controlled trials.","authors":"Talavera, Armando; Teixeira, Larissa; Klein, Benjamin; Lopes, Rodolfo A; Urina-Jassir, Daniela; Navalha, Denilsa D P; Bettinotti, Branco G M; Fernandez, Nicole; Urina-Triana, Miguel; Welty, Francine K; Mihos, Christos G; Elajami, Tarec K","year":2025,"journal":"Diabetes, obesity & metabolism, 27(12), 7030-7039","doi":"10.1111/dom.70102","pmid":"40937512","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"HF events: RR 0.40 (p=0.003). CV mortality: RR 0.79 (NS). All-cause mortality: RR 0.98 (NS). KCCQ-CSS: +7.23 points. Weight: -9.76 kg. 6MWD: +16.54 m. GI AE discontinuation: RR 4.01. SAEs: RR 0.66 (NS). 3 RCTs, 1,876 patients.","whyItMatters":"This precisely quantifies the HFpEF benefit: dramatic HF event reduction and quality improvement, but no mortality benefit yet. This defines realistic expectations for GLP-1 drugs in HFpEF.","specificNumbers":"","methodology":"Systematic review and meta-analysis. Embase, PubMed, Cochrane. 3 RCTs. Random-effects model. 1,876 patients with obesity + HFpEF. Mean follow-up 69.3 weeks.","limitations":"Only 3 RCTs available. ~70-week follow-up may be too short for mortality. GI discontinuation (RR 4.01) may limit real-world adoption. Different GLP-1 drugs pooled."},{"rthcId":"RPEP-13751","title":"12-Month Weight Loss and Adherence Predictors in a Real-World UK Tirzepatide-Supported Digital Obesity Service: A Retrospective Cohort Analysis.","authors":"Talay, Louis; Hom, Jason; Scott, Tamara; Ahuja, Neera","year":2025,"journal":"Healthcare (Basel, Switzerland), 14(1)","doi":"10.3390/healthcare14010060","pmid":"41516991","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"19,693 patients. 12-month adherence: 27% (5,322). Adherent weight loss: 22.6% ± 7.46%. Full cohort (LOCF): 13.6% ± 10.85%. Best predictor: consistent weekly engagement (tracking, coaching). Intensive daily tracking and rapid early loss predicted dropout.","whyItMatters":"At 22.6%, this is among the highest real-world weight loss results ever reported, demonstrating that tirzepatide + comprehensive digital support can approach clinical trial efficacy. The adherence insight—moderate pacing beats intensive tracking—is directly actionable.","specificNumbers":"","methodology":"Retrospective cohort of 19,693 Juniper UK DWLS patients on tirzepatide. LOCF for full cohort. Logistic regression (adherence predictors) and linear regression (weight loss predictors).","limitations":"Retrospective. 27% adherence means 73% dropped out. Self-selected population. No control group. Digital literacy may bias participation."},{"rthcId":"RPEP-13752","title":"Switching anti-CGRP monoclonal antibodies in chronic migraine: real-world observations of erenumab, fremanezumab and galcanezumab.","authors":"Talbot, Jamie; Stuckey, Rebecca; Wood, Natasha; Gordon, Alexander; Crossingham, Ginette; Weatherby, Stuart","year":2025,"journal":"European journal of hospital pharmacy : science and practice, 32(2), 178-185","doi":"10.1136/ejhpharm-2023-003779","pmid":"38182276","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Overall: -1.2 red days (NS), 15% ≥50% responders, 33% ≥30% responders. Switched for ineffectiveness only: significant ↓headache days (p=0.044). Side effects: improved/resolved in 12/20, new symptoms in 8/20. 66 switches in 54 patients.","whyItMatters":"When patients fail one anti-CGRP drug, clinicians need to know whether trying another is worthwhile. This study suggests switching for ineffectiveness (not side effects) has the best chance of success.","specificNumbers":"","methodology":"Retrospective analysis. 54 chronic migraine patients, 66 switch instances. Headache diary data. 6-month post-switch follow-up. Primary outcome: red days at 3 months.","limitations":"Retrospective. Small sample (54 patients). No control group. Multiple switch directions. Modest overall effects."},{"rthcId":"RPEP-13753","title":"Real-world Associations Between GLP-1 Receptor Agonist Use and Diabetic Retinopathy Accounting for Longitudinal Glycemic Control.","authors":"Talebi, Ramin; Fortes, Blake H; Yu, Fei; Coleman, Anne L; Tsui, Irena","year":2025,"journal":"Retina (Philadelphia, Pa.)","doi":"10.1097/IAE.0000000000004507","pmid":"40334190","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"DR: HR 0.31 (0.26-0.37, p<0.001). DME: HR 0.40 (0.27-0.59, p<0.001). Treatment-requiring DR/DME: HR 0.18 (0.08-0.40, p<0.001). 10-year follow-up. Adjusted for longitudinal HbA1c changes.","whyItMatters":"This is the strongest evidence yet that GLP-1 drugs protect against diabetic eye disease—accounting for the HbA1c change confounder that has plagued prior studies. An 82% reduction in treatment-requiring disease is clinically transformative.","specificNumbers":"","methodology":"Longitudinal retrospective cohort. 10-year follow-up from T2DM diagnosis. Cox regression adjusted for 10+ variables including longitudinal HbA1c change. Survival analyses.","limitations":"Retrospective. Cannot fully exclude confounding. GLP-1 users may differ from non-users. Specific GLP-1 drugs not compared. \"GLP-1 RA use\" definition may vary."},{"rthcId":"RPEP-13754","title":"Vasoactive neuropeptide dysregulation: A novel mechanism of microvascular dysfunction in vascular cognitive impairment.","authors":"Tambo, Willians; Powell, Keren; Wadolowski, Steven; Unadkat, Prashin; Chang, Eric H; LeDoux, Christopher; Sciubba, Daniel; Wang, Ping; Huerta, Patricio; Li, Chunyan","year":2025,"journal":"Alzheimer's & dementia : the journal of the Alzheimer's Association, 21(11), e70925","doi":"10.1002/alz.70925","pmid":"41268782","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Vasoactive neuropeptide dysregulation = primary VCI driver. Microvascular constriction: earliest event, precedes amyloid. CGRP depletion: key driver. CGRP supplementation: prevented vasoconstriction + improved cognition. Capillary constriction precedes and drives amyloid accumulation.","whyItMatters":"This reverses conventional thinking: microvascular damage driven by neuropeptide dysregulation may CAUSE amyloid accumulation (not the other way around), with CGRP supplementation as a potential therapeutic approach for vascular dementia.","specificNumbers":"","methodology":"Chronic cerebral hypoperfusion rat model. Proteomic analysis. Neuropeptide and non-neuropeptide marker evaluation across VCI severities. Cognitive testing. CGRP supplementation experiments.","limitations":"Rat model. CGRP supplementation method not detailed. Human VCI pathophysiology may differ. Proteomic findings need independent validation."},{"rthcId":"RPEP-13755","title":"Efficacy of GLP-1 receptor agonists and dual GLP-1/GIP receptor agonists in managing MALFD: a meta-analysis of randomized controlled trials.","authors":"Tamilwanan, Surtika; Aziz, Zoriah; Rong, Lim Yan; Bitar, Ahmad Naoras; Zarzour, Raghdaa Hamdan Al; Alshehade, Salah A","year":2025,"journal":"BMC gastroenterology, 25(1), 765","doi":"10.1186/s12876-025-04358-0","pmid":"41146009","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1RA liver fat: -3.37% (p significant). Dual GLP-1/GIP: -7.15% (p significant). Dual > mono for liver fat (p significant). ↓ALT, AST, glycemic markers. >48 weeks needed for optimal results. 26 RCTs, 3,453 patients. GRADE evaluated.","whyItMatters":"MAFLD affects 30% of the global population with few effective treatments. Showing dual GLP-1/GIP drugs are 2x more effective than GLP-1 alone for liver fat helps clinicians choose the optimal agent.","specificNumbers":"","methodology":"Systematic review and meta-analysis. PubMed, Cochrane, Web of Science, Scopus through July 2025. 26 RCTs. Subgroup analyses by receptor target, duration, control, age. GRADE framework.","limitations":"Heterogeneous trial designs. Different GLP-1 and dual agents pooled. MAFLD definitions varied. Long-term histological outcomes limited."},{"rthcId":"RPEP-13756","title":"Effects of subcutaneous or oral semaglutide on cardiovascular outcomes in patients with type 2 diabetes mellitus: a meta-analysis of randomized controlled trials.","authors":"Tan, Sihua; Yin, Yangguang; Lu, Juexiu","year":2025,"journal":"Frontiers in cardiovascular medicine, 12, 1731127","doi":"10.3389/fcvm.2025.1731127","pmid":"41472878","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Primary CV outcome: HR 0.83 (0.76-0.91). Nonfatal MI: HR 0.79 (0.67-0.92). Revascularization: HR 0.71 (0.61-0.83). HF hospitalization: HR 0.85 (0.72-1.00). CV death, all-cause death, stroke: NS. Oral = subcutaneous efficacy. 4 RCTs, 19,663 patients. GRADE: moderate-high.","whyItMatters":"Confirming oral semaglutide provides identical cardiovascular protection as injectable removes a key prescribing uncertainty. Patients can choose pill or injection without compromising heart protection.","specificNumbers":"","methodology":"PROSPERO-registered meta-analysis (CRD420251147337). PubMed, Embase, Cochrane, Web of Science. 4 RCTs. Fixed/random effects. Sensitivity, subgroup, GRADE analyses.","limitations":"4 trials only. Different trial populations. Cannot determine if dose equivalence is maintained across all CV outcomes. Mortality not significantly reduced."},{"rthcId":"RPEP-13757","title":"Comparative effectiveness of GLP-1 RAs and other glucose-lowering therapies among Medicare Advantage beneficiaries with T2D and ASCVD.","authors":"Tan, Xi; Liang, Yuanjie; Xie, Lin; Gutierrez, Cynthia; Harton, Joanna; Muhammad, Chalak; Swift, Caroline; de Havenon, Adam","year":2025,"journal":"Current medical research and opinion, 41(10), 1787-1798","doi":"10.1080/03007995.2025.2577762","pmid":"41122783","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"vs ONIGLTs: IS -18%, MI -14%, 2P-MACE -17%, 3P-MACE -28%, 5P-MACE -27%. vs SGLT2i: 2P-MACE -14%, 3P-MACE -15%, 5P-MACE -14%. Semaglutide: lowest risk vs SGLT2i for all outcomes. 41,835 GLP-1 + 77,599 ONIGLT matched patients.","whyItMatters":"This is the largest Medicare comparison showing GLP-1 drugs outperform even SGLT2 inhibitors for cardiovascular protection in established ASCVD—supporting GLP-1 drugs as first-choice for this high-risk population.","specificNumbers":"","methodology":"Observational cohort from Optum Medicare Advantage (2007-2024). Propensity score matching. 41,835 GLP-1RA + 77,599 ONIGLT. Incidence rates and time to first event.","limitations":"Observational. Medicare population (≥65). US-specific. Propensity matching cannot eliminate all confounders. Early post-launch GLP-1 use may have selection bias."},{"rthcId":"RPEP-13758","title":"GLP-1 receptor agonists as an adjunct to bariatric surgery for weight loss and metabolic outcome improvement: a systematic review and meta-analysis.","authors":"Tan, Yee Wen; Shang, Mengge; Davis, Sean; Gananadha, Sivakumar","year":2025,"journal":"Langenbeck's archives of surgery, 410(1), 295","doi":"10.1007/s00423-025-03831-4","pmid":"41071360","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"All GLP-1RAs: significant weight/BMI reduction proportional to treatment duration. Hierarchy: tirzepatide > semaglutide > liraglutide. Semaglutide > liraglutide for ≥10% and ≥15% weight loss. Cardiometabolic improvements: glucose, BP, cholesterol, liver. Adverse effects: mild GI. 19 studies.","whyItMatters":"Weight regain after bariatric surgery affects 20-35% of patients and previously had few effective non-surgical options. GLP-1 drugs provide a pharmacological rescue strategy that avoids revision surgery.","specificNumbers":"","methodology":"PRISMA systematic review and meta-analysis. PubMed, MEDLINE, Embase, Cochrane. 19 studies. Adults ≥18 with IWL or WR after bariatric surgery. 3-24 month interventions.","limitations":"Mostly observational studies. Short to moderate follow-up. Few RCTs. Tirzepatide data limited. Long-term post-surgical safety needs evaluation."},{"rthcId":"RPEP-13759","title":"Effect of GLP-1 receptor agonists on bone mineral density, bone metabolism markers, and fracture risk in type 2 diabetes: a systematic review and meta-analysis.","authors":"Tan, Yimei; Liu, Shuanghua; Tang, Qizhi","year":2025,"journal":"Acta diabetologica, 62(5), 589-606","doi":"10.1007/s00592-025-02468-5","pmid":"39985672","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13760","title":"Possible mechanisms of action of glucagon-like peptide-1 receptor agonists on blood pressure beyond body weight.","authors":"Tanaka, Masami; Itoh, Hiroshi","year":2025,"journal":"Hypertension research : official journal of the Japanese Society of Hypertension, 48(12), 3159-3171","doi":"10.1038/s41440-025-02418-2","pmid":"41102420","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BP lowering beyond weight: NHE3 inhibition → natriuresis, ↓angiotensin II activity, ↑vasodilation. Acute: inconsistent BP response. Chronic: consistent hypotensive effect. Improves morning surge + nocturnal HTN. Triple action: glucose + weight + BP lowering.","whyItMatters":"Hypertension is the #1 cardiovascular risk factor. Understanding that GLP-1 drugs lower BP through direct renal and vascular mechanisms—not just weight loss—strengthens the case for their use in hypertensive diabetic patients.","specificNumbers":"","methodology":"Narrative review of human and animal studies on GLP-1/GLP-1RA blood pressure mechanisms.","limitations":"Mostly preclinical mechanism data. Human BP data from secondary trial analyses. Mediation analysis suggests but cannot prove weight-independent mechanisms."},{"rthcId":"RPEP-13761","title":"Continuation, Resumption, and Withdrawal Rates of CGRP-mAb Treatment for Migraine Under Real-World Clinical Conditions in Which Patients Are Free to Choose Own Treatment.","authors":"Tanei, Takafumi; Yamashita, Satoshi; Maesawa, Satoshi; Nishimura, Yusuke; Ishizaki, Tomotaka; Nagashima, Yoshitaka; Suzuki, Takahiro; Hamasaki, Hajime; Yamamoto, Shun; Wakabayashi, Toshihiko; Saito, Ryuta","year":2025,"journal":"Neurology international, 18(1)","doi":"10.3390/neurolint18010003","pmid":"41591077","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Continuation: 93.2% (3m), 80.2% (6m), 68.9% (9m), 58.8% (12m), 55.4% (18m), 51.7% (24m). Resumption: 76.8%. Permanent withdrawal: 20.7%. HIT-6 and MSQ significantly improved at all points. No predictors of resumption vs withdrawal. 146 patients, patient-directed treatment choice.","whyItMatters":"When patients control their own treatment decisions—the most realistic scenario—over half continue CGRP drugs at 2 years and >75% who stop eventually return. This is much more optimistic than insurance-mandated persistence data.","specificNumbers":"","methodology":"Prospective observational study. 146 treatment-naïve migraine patients. Free patient choice to continue/stop/resume. HIT-6 and MSQ assessment. ≥3 month follow-up requirement.","limitations":"Single center. 146 patients. Selection of treatment-naïve may bias toward more motivated patients. Japanese population. Insurance coverage may affect access."},{"rthcId":"RPEP-13762","title":"Glucagon-like peptide-1 receptor agonist in myocardial infarction and atherosclerotic cardiovascular disease risk reduction: a comprehensive meta-analysis of number needed to treat, efficacy and safety.","authors":"Tang, Ansel Shao Pin; Hsu, Jovan Teng Yuan; Chong, Sheena Kar Shuan; Quek, Jingxuan; Shek, Genevieve; Sulaimi, Farisah; Chan, Kai En; Anand, Vickram Vijay; Chong, Bryan; Mehta, Anurag; Toh, Sue-Anne; Muthiah, Mark; Dimitriadis, Georgios K; le Roux, Carel W; Chan, Mark Yan-Yee; Mamas, Mamas Andreas; Chin, Yip Han; Chew, Nicholas W S","year":2025,"journal":"Cardiovascular diabetology, 24(1), 285","doi":"10.1186/s12933-025-02840-3","pmid":"40652242","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"MI: RR 0.86 (p<0.01), NNT 207. CV mortality: RR 0.87 (p<0.01), NNT 170. MACE: RR 0.87 (p<0.01), NNT 67. Stroke: RR 0.88 (p<0.01), NNT 335. Higher BMI → greater MI reduction (β=-0.09, p=0.03). GI AEs: RR 1.55, NNTH 9. 25 studies, 109,846 patients, 3.48 years.","whyItMatters":"NNT values make abstract risk ratios clinically actionable: treating 67 patients for 3.5 years prevents one MACE event, 170 prevents one CV death, 207 prevents one MI. These numbers help prescribers and patients weigh benefits versus costs.","specificNumbers":"","methodology":"Pairwise meta-analysis of 25 unique RCTs from Medline/Embase. Random-effects model. Primary: MI. Secondary: individual ASCVD components. Meta-regression for BMI. NNT/NNTH calculated.","limitations":"Pooled different GLP-1 drugs. Follow-up duration varied. NNT depends on baseline risk. GI side effects common (NNTH 9) but mostly mild."},{"rthcId":"RPEP-13763","title":"TAZ-hTrap: A Rationally Designed, Disulfide-Stapled Tead Helical Hairpin Trap to Selectively Capture Hippo Signaling Taz With Potent Antigynecological Tumor Activity.","authors":"Tang, Bin; Du, Yu; Wang, Jun","year":2025,"journal":"Journal of molecular recognition : JMR, 38(2), e3111","doi":"10.1002/jmr.3111","pmid":"39626959","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"25-mer stapled helical hairpin from TEAD. Disulfide bridge stabilizes native conformation. Minimized entropy penalty → improved TAZ binding. Selective for TAZ over noncognate proteins. Potent cytotoxicity on gynecological tumors (cervical, ovarian, endometrial). Confirmed by CD, FP, and viability assays.","whyItMatters":"The Hippo/TAZ pathway drives multiple gynecological cancers but has been considered \"undruggable.\" This stapled peptide demonstrates that protein-protein interactions can be disrupted by rationally designed peptide traps.","specificNumbers":"","methodology":"Rational peptide design from TEAD protein structure. Molecular dynamics and energetics simulation. Disulfide stapling. Circular dichroism (CD). Fluorescence polarization (FP). Cell viability assays on gynecological tumor lines.","limitations":"In vitro cytotoxicity only. No in vivo tumor models. Pharmacokinetics, stability, and delivery not assessed. Cell viability does not prove in vivo anti-tumor efficacy."},{"rthcId":"RPEP-13764","title":"Unveiling the inhibition mechanism of host-defense peptide cathelicidin LL-37 on the amyloid aggregation of the human islet amyloid polypeptide.","authors":"Tang, Huayuan","year":2025,"journal":"Nanoscale, 17(9), 5116-5127","doi":"10.1039/d4nr05075d","pmid":"39871583","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"LL-37 binds hIAPP monomers, oligomers, and fibrils. Mechanism: hydrophobic + pi-pi interactions at amyloidogenic regions. Monomer/oligomer: LL-37 N/C-terminal residues prevent self-association. Fibrils: geometric incompatibility blocks elongation. Links infection defense with amyloid disease.","whyItMatters":"Type 2 diabetes involves amyloid deposits in the pancreas that kill beta-cells. Understanding how LL-37 prevents this aggregation could lead to dual-function therapeutics that fight both infections and amyloid diseases.","specificNumbers":"","methodology":"All-atom discrete molecular dynamics (DMD) simulations of LL-37 with hIAPP monomers, oligomers, and fibril seeds. Interaction analysis, conformational dynamics, key residue identification.","limitations":"Computational study only—no experimental validation of proposed mechanism. Simulated conditions may not replicate physiological concentrations. All-atom DMD has inherent approximations."},{"rthcId":"RPEP-13765","title":"Cardiovascular and kidney outcomes of GLP-1 receptor agonists in adults with obesity: A target trial emulation study.","authors":"Tang, Huilin; Lu, Yiwen; Zhang, Bingyu; Zhou, Ting; Zhang, Dazheng; Chen, Jiajie; Chen, Yong; Asch, David A; Chen, Yong","year":2025,"journal":"Diabetes, obesity & metabolism, 27(11), 6527-6536","doi":"10.1111/dom.70054","pmid":"40874398","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"MACE HR 0.76 (0.72-0.81). MAKE HR 0.64 (0.55-0.74). Mortality HR 0.49 (0.42-0.57). Depression HR 0.63. Suicidal ideation HR 0.42. Substance use HR 0.58. No increased: pancreatitis (HR 1.17 NS), hypoglycemia (HR 1.08 NS), GI symptoms (HR 0.99 NS). 140,169 matched pairs.","whyItMatters":"This is the largest and most comprehensive study of GLP-1 drugs in non-diabetic obesity. The mental health improvements—58% less suicidal ideation—directly counter safety concerns while demonstrating benefits beyond metabolic outcomes.","specificNumbers":"","methodology":"Target trial emulation. TriNetX EHR data (July 2021-May 2025). 140,169 matched pairs (280,338 total). Propensity score matching. Cox models. GLP-1RAs vs other AOMs in non-diabetic obesity.","limitations":"Observational target trial emulation. Mean follow-up only ~1 year. US EHR data. Cannot fully exclude confounding. Mental health outcomes may reflect healthier baseline in GLP-1 users."},{"rthcId":"RPEP-13766","title":"Neuropeptide Y as a Prognostic Biomarker in Electrical Storm.","authors":"Tang, Jianjun; Liu, Chengfeng; Wang, Zhuo; Zhu, Tongjian; Zhong, Min; Li, Yasai; Chen, Mingxian","year":2025,"journal":"JACC. Clinical electrophysiology, 11(4), 655-663","doi":"10.1016/j.jacep.2024.11.021","pmid":"39918460","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Refractory ES: significantly higher NPY vs controls. NPY threshold: 44.4 pg/mL (sensitivity 0.91, specificity 0.90). High NPY: significantly worse survival (Kaplan-Meier). Cox: NPY independently associated with mortality (95% CI 0.89-0.99). 95 patients (62 control, 33 refractory).","whyItMatters":"Electrical storm is a cardiac emergency with high mortality. Having a blood test (NPY >44.4 pg/mL) that identifies high-risk patients with 91% sensitivity could enable earlier aggressive intervention.","specificNumbers":"","methodology":"Prospective cohort. 95 ES patients (62 drug-responsive, 33 refractory). Plasma NPY by ELISA. ROC analysis. Kaplan-Meier survival. Cox proportional hazards.","limitations":"Small study (95 patients). Single center. NPY as a single measurement. Prospective but not validated externally. Cannot determine if NPY causes or reflects worse outcomes."},{"rthcId":"RPEP-13767","title":"Long-term cost-effectiveness of tirzepatide for individuals with type 2 diabetes and comorbid obesity.","authors":"Tang, Man; Shi, Lizheng; Guan, Dawei; Winberg, Debra; Tang, Tiange; Shao, Hui; Fonseca, Vivian","year":2025,"journal":"Diabetes, obesity & metabolism, 27(8), 4288-4299","doi":"10.1111/dom.16466","pmid":"40452343","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"TZP 15 mg: cost-saving (-,409) + 0.69 QALYs + 0.58 life-years. TZP 10 mg: +,855 cost, 0.60 QALYs, ICER ,092/QALY. Both: >98.5% probability cost-effective at K WTP. Treatment effects assumed for 5 years.","whyItMatters":"Cost-effectiveness drives insurance coverage and access. Showing tirzepatide 15 mg is actually cost-SAVING (not just cost-effective) provides the strongest economic argument for coverage.","specificNumbers":"","methodology":"BRAVO Diabetes Model (validated). 30-year time horizon. US healthcare perspective. SURMOUNT-2 trial efficacy data. GoodRx medication prices. One-way + probabilistic sensitivity analysis.","limitations":"Model-based projections. Treatment effect assumed 5 years (conservative). US prices. SURMOUNT-2 population. Drug prices may change."},{"rthcId":"RPEP-13768","title":"Assessment of innate immune response modulating impurities (IIRMI) in synthetic peptide drugs (liraglutide).","authors":"Tang, Yangming; Tang, Chao; Lu, Xiaojie; Xing, Xinhui","year":2025,"journal":"Biochemical and biophysical research communications, 771, 151967","doi":"10.1016/j.bbrc.2025.151967","pmid":"40398094","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"No significant immunogenicity difference: synthetic vs recombinant liraglutide. Novel PBMC-based IIRMI detection method established. Fresh PBMCs from multiple volunteers. TLR/NOD ligand challenge testing. FDA tentative approval of generic June 2024.","whyItMatters":"As generic synthetic peptide drugs enter the market, ensuring equivalent immunogenicity is critical. This PBMC-based method detects unknown trace impurities that cell line-based systems might miss.","specificNumbers":"","methodology":"PBMC-based assays with fresh cells from different volunteers. Liraglutide ± TLR/NOD ligands. Comparison of recent and aged products. Cytokine/chemokine measurement.","limitations":"In vitro assay. PBMC response may not predict in vivo immunogenicity. Limited number of volunteers. Only liraglutide tested. Long-term immunogenicity not assessed."},{"rthcId":"RPEP-13769","title":"A novel function of short cationic peptide FP-CATH9 without antimicrobial activity reverses resistance to minocycline in common multidrug-resistant gram-negative bacteria.","authors":"Tang, Yingqi; Liu, Jiye; Yan, Jiani; Xie, Zhixiong; Zhong, Lipeng","year":2025,"journal":"Microbiology spectrum, 13(4), e0290824","doi":"10.1128/spectrum.02908-24","pmid":"39998408","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"FP-CATH9: 9 amino acids, no antibacterial activity alone. Reverses minocycline resistance in MDR gram-negative bacteria (E. coli, K. pneumoniae, A. baumannii, P. aeruginosa). Mechanism: inhibits efflux → ↑intracellular minocycline. Low hemolysis + cytotoxicity. In vivo: 80% larval survival with combination.","whyItMatters":"Antibiotic resistance is a global crisis. A non-toxic peptide that makes existing antibiotics effective again—without having antimicrobial activity itself—is a novel approach to the resistance problem.","specificNumbers":"","methodology":"Double-dilution dose-response. Checkerboard synergy (FICI). Ethidium bromide efflux assay. Hemolysis and RAW264.7 cytotoxicity. Galleria mellonella MDR K. pneumoniae infection model.","limitations":"Larval model only. Minocycline-specific—unknown if it works with other antibiotics. Mechanism of efflux inhibition not fully characterized. Manufacturing of specific peptide fragments needs evaluation."},{"rthcId":"RPEP-13770","title":"The Role of Glucagon-Like Peptide-1 Receptor Agonists in the Treatment of Alcohol Use Disorder: Current Evidence and Future Directions.","authors":"Tanguturi Yella, Sree Sudha; Kota Sesha Brahma Sree, Krishna Sasanka; Mahato, Sumit Kumar","year":2025,"journal":"Journal of clinical psychopharmacology, 45(4), 372-375","doi":"10.1097/JCP.0000000000002010","pmid":"40184516","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Animal: GLP-1R activation ↓alcohol intake, ↓relapse. Mechanism: brain reward pathway modulation (mesolimbic dopamine). Clinical: some reduction in heavy drinking days (especially with comorbid obesity). Gaps: extended studies, diverse trials, pharmacogenomics needed.","whyItMatters":"AUD treatment has only 3 FDA-approved drugs with limited efficacy. GLP-1 drugs, already approved for diabetes/obesity, offer a novel mechanism targeting reward pathways and could be rapidly evaluated for AUD.","specificNumbers":"","methodology":"Narrative review of preclinical (animal) and clinical evidence on GLP-1RA effects on alcohol-related behaviors.","limitations":"Narrative review. Animal data may not translate directly. Clinical trials are small and early. Not all GLP-1 drugs may be equally effective. AUD has complex biopsychosocial factors."},{"rthcId":"RPEP-13771","title":"Cardiometabolic Benefits and Risks of Sodium-Glucose Co-Transporter-2 (SGLT-2) Inhibitor and Glucagon-Like Peptide-1 (GLP-1) Receptor Agonist Combination Therapy in Type 2 Diabetes: A Systematic Review.","authors":"Tantawy, Dalia; Musa Rabih, Maram Rabih; Ibrahim Mohamed, Razan Seifeldin; Abdelrahman Ali, Malaz Omer; Mohammed Saad Aldeen, Rayan Saad Aldeen; Ahmed Abdelkarim, Ali Omer; Awadalkreem Mohamedzain, Tawasul Greeballah","year":2025,"journal":"Cureus, 17(11), e96218","doi":"10.7759/cureus.96218","pmid":"41211260","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1RA reduced MACE/HFH regardless of SGLT2i background. SGLT2i benefits maintained with GLP-1RA. Combination: superior HbA1c, weight, SBP reduction. No new safety signals. Manageable GI and genital infection risks. 9 RCTs (2020-2025).","whyItMatters":"Guidelines now recommend both drug classes for high-risk T2DM. This review confirms the combination is synergistic and safe, supporting dual therapy over sequential monotherapy.","specificNumbers":"","methodology":"PRISMA systematic review. PubMed, Scopus, Embase, Web of Science (2020-2025). 9 RCTs including CVOTs and mechanistic studies. Cochrane RoB 2.","limitations":"Post-hoc analyses from trials not designed for combination. Dedicated prospective combination trials still needed. Cost/access barriers to dual therapy."},{"rthcId":"RPEP-13772","title":"Microbiota and enteric nervous system crosstalk in diabetic gastroenteropathy: bridging mechanistic insights to microbiome-based therapies.","authors":"Tao, Wang; Yu, Yunfeng; Tan, Danni; Huang, Xiangning; Huang, Jiawang; Lin, Chuanquan; Yu, Rong","year":2025,"journal":"Frontiers in cellular and infection microbiology, 15, 1603442","doi":"10.3389/fcimb.2025.1603442","pmid":"40861487","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"DGE driven by ENS impairment (not just vagus). Microbiota-ENS axis: SCFAs, bile acids, tryptophan. Peptide mediators: GLP-1, ghrelin, VIP, acetylcholine, NO. Microbiome therapies (probiotics, prebiotics, FMT): repair ENS + alleviate DGE. >50% of diabetics have GI symptoms.","whyItMatters":"Over half of diabetic patients have GI symptoms that worsen glucose control. Understanding the microbiota-ENS-peptide axis reveals new therapeutic targets beyond traditional motility drugs.","specificNumbers":"","methodology":"Narrative review of microbiota-ENS interactions in diabetic gastroenteropathy with focus on neuropeptide mediators.","limitations":"Narrative review. Most microbiome-ENS evidence is preclinical. FMT evidence in diabetic GI dysfunction is limited. Peptide mediator contributions not quantified."},{"rthcId":"RPEP-13773","title":"No Difference in Short-term Surgical Outcomes From Semaglutide Treatment for Type 2 Diabetes Mellitus After Cervical Decompression and Fusion: A Propensity Score-matched Analysis.","authors":"Tao, Xu; Ranganathan, Sruthi; Van Halm-Lutterodt, Nicholas; Garcia-Vargas, Julia; Wu, Andrew; Karnati, Janesh; Shankar, Sachin; Agyeman, Nana; Ashraf, Ahmed; Barve, Parikshit; Childress, Kelly; Adogwa, Owoicho","year":2025,"journal":"Spine, 50(8), 515-521","doi":"10.1097/BRS.0000000000005099","pmid":"39034750","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Surgical complications: OR 1.26 (0.83-1.93, NS). 30-day readmission: OR 0.83 (NS). 90-day readmission: OR 0.89 (NS). 298 matched pairs. PearlDiver Database 2010-2021.","whyItMatters":"Surgeons are increasingly encountering patients on GLP-1 drugs. This study provides reassurance that semaglutide does not impair surgical healing or increase complications in spine surgery.","specificNumbers":"","methodology":"Retrospective propensity-matched cohort from PearlDiver Database. 596 T2DM patients (298 semaglutide, 298 control). Matched on age, sex, CCI. Multivariate regression.","limitations":"Retrospective. Short-term (<6 month) outcomes only. PearlDiver Database limitations. Cannot assess long-term fusion outcomes. Relatively small matched cohort."},{"rthcId":"RPEP-13774","title":"Evidence Report on the Safety of Gastrointestinal Endoscopy in Patients on Glucagon-like Peptide-1 Receptor Agonists: A Systematic Review and Meta-Analysis.","authors":"Tarar, Zahid Ijaz; Farooq, Umer; Chaudhry, Ahtshamullah; Gandhi, Mustafa; El Alayli, Abdallah; Ayoub, Mark; Singh, Baltej; Daglilar, Ebubekir; Thosani, Nirav","year":2025,"journal":"Diagnostics (Basel, Switzerland), 15(6)","doi":"10.3390/diagnostics15060770","pmid":"40150111","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"RGC: OR 6.30 (5.30-7.49, I²=0%). Aborted: OR 5.50 (3.25-9.32, I²=0%). Repeated: OR 2.19 (1.42-3.38, I²=0%). Aspiration: OR 1.26 (0.86-1.87, NS, I²=34%). Tirzepatide: highest RGC (18.9%). Colonoscopy prep: ↓RGC (OR 0.26). 32,144 GLP-1 + 73,273 controls.","whyItMatters":"GLP-1 drugs slow gastric emptying, raising fears about aspiration during endoscopy. This large analysis shows the aspiration risk is NOT significantly elevated—the practical impact is more aborted/repeated procedures, manageable with dietary preparation.","specificNumbers":"","methodology":"Systematic review and meta-analysis. 12 studies, 105,515 patients. Random effects model. Predictive factors analysis. Sensitivity analysis.","limitations":"Heterogeneous GLP-1 drug types and doses. Definition of RGC varied. Aspiration events rare (small numbers). Cannot determine optimal GLP-1 hold time."},{"rthcId":"RPEP-13775","title":"Recent advances in incretin-based therapy for MASLD: from single to dual or triple incretin receptor agonists.","authors":"Targher, Giovanni; Mantovani, Alessandro; Byrne, Christopher D; Tilg, Herbert","year":2025,"journal":"Gut, 74(3), 487-497","doi":"10.1136/gutjnl-2024-334023","pmid":"39592207","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1RA (semaglutide): phase 3 for MASH. Dual agonists (tirzepatide, survodutide): phase 2 histological improvements. Triple agonist (retatrutide): most efficacy data emerging. Escalating efficacy with more receptor targets. Hepatoprotective beyond weight loss.","whyItMatters":"MASLD/MASH has had no approved pharmacotherapy until recently. Incretin-based drugs offer the first effective treatment class, with escalating potency as more receptor targets are engaged.","specificNumbers":"","methodology":"Narrative review of clinical trial evidence for single, dual, and triple incretin agonists in MASLD/MASH.","limitations":"Most evidence from phase 2 trials. Long-term liver outcome data limited. Optimal receptor combination unclear. Not all patients respond equally."},{"rthcId":"RPEP-13776","title":"Risk of all-cause death and pancreatic events following GLP-1 RA initiation in people with obesity or type 2 diabetes: observations from a federated research network.","authors":"Tartaglia, Enrico; Bucci, Tommaso; Rossi, Michele; Rigutini, Andrea Galeazzo; Askarinejad, Amir; Alam, Uazman; Nabrdalik, Katarzyna; Boriani, Giuseppe; Lip, Gregory Y H","year":2025,"journal":"Cardiovascular diabetology, 24(1), 438","doi":"10.1186/s12933-025-02986-0","pmid":"41257737","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"All-cause death: HR 0.554 (0.542-0.566). Composite pancreatitis: HR 1.062 (1.023-1.102). Acute pancreatitis: HR 1.058 (1.015-1.103), mainly first 6 months. Chronic pancreatitis: NS. Pancreatic cancer: NS. <65: greater mortality benefit. 1.56M GLP-1 users vs 18.65M non-users.","whyItMatters":"This is the largest GLP-1 safety/benefit analysis ever conducted. The 45% mortality reduction is extraordinary, while the 6% pancreatitis increase is manageable—clearly favorable benefit-risk ratio.","specificNumbers":"","methodology":"Retrospective TriNetX federated network study (2018-2024). 1:1 propensity score matching. Cox regression. Sensitivity analyses (early vs late). Subgroup analyses (age, sex, comorbidities).","limitations":"Observational (healthy user bias possible). Propensity matching cannot fully eliminate confounding. GLP-1 users inherently differ from non-users. TriNetX data quality varies."},{"rthcId":"RPEP-13777","title":"Decoding PACAP signaling: Splice variants, pathways and designer drugs.","authors":"Tasma, Zoe; Hay, Debbie L","year":2025,"journal":"Cephalalgia : an international journal of headache, 45(8), 3331024251363560","doi":"10.1177/03331024251363560","pmid":"40767099","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"PACAP/VIP: 3 canonical receptors (PAC1, VPAC1, VPAC2) + 2 proposed (GPR55, MRGPRX2). Extensive splice variant diversity. Anti-PACAP antibody: clinical migraine efficacy. Receptor signaling: membrane + endosomal. Accessory proteins modify responses. \"Designer drug\" opportunities.","whyItMatters":"With anti-PACAP antibody showing clinical migraine efficacy, understanding the full complexity of PACAP/VIP signaling enables development of more selective, effective drugs with fewer side effects.","specificNumbers":"","methodology":"Narrative review of PACAP/VIP system biology, receptor pharmacology, splice variants, and drug development opportunities.","limitations":"Narrative review. Many receptor variants poorly characterized. Proposed non-canonical receptors need confirmation. In vivo relevance of splice variants unclear."},{"rthcId":"RPEP-13778","title":"Development and pharmacological characterization of novel multi- calcitonin gene-related peptide and pituitary adenylate cyclase-activating peptide receptor antagonists.","authors":"Tasma, Zoe; Siow, Andrew; Harris, Paul W R; Brimble, Margaret A; Hay, Debbie L; Walker, Christopher S","year":2025,"journal":"Headache, 65(7), 1064-1079","doi":"10.1111/head.14916","pmid":"39995298","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Three multi-receptor antagonists created by click chemistry. Maintained potency vs parental antagonists at all receptors (CGRP-R, AMY1, PAC1, VPAC1, VPAC2). Position 38 linkage: enhanced CGRP antagonism. Validated in Cos7 cells AND spinal cord cultures (endogenous receptors).","whyItMatters":"Both CGRP and PACAP drive migraine, but current drugs target only one. A single molecule blocking both could provide superior migraine prevention for patients who do not fully respond to CGRP-only therapy.","specificNumbers":"","methodology":"Click chemistry (1,3-dipolar cycloaddition) linking CGRP8-37 to PACAP6-38 at positions 21, 34, or 38. cAMP accumulation assays in Cos7 cells. Pain-relevant rat spinal cord cultures.","limitations":"In vitro proof of concept. Peptide antagonists have poor in vivo pharmacokinetics. No animal migraine model testing. Click chemistry linkage may affect in vivo stability."},{"rthcId":"RPEP-13779","title":"Where are we now? Biased signalling of Class B G protein-coupled receptor-targeted therapeutics.","authors":"Tasma, Zoe; Garelja, Michael L; Jamaluddin, Aqfan; Alexander, Tyla I; Rees, Tayla A","year":2025,"journal":"Pharmacology & therapeutics, 270, 108846","doi":"10.1016/j.pharmthera.2025.108846","pmid":"40216261","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Class B GPCRs: 15 peptide hormone receptors. Recent approvals: migraine (CGRP), diabetes (GLP-1), obesity. Biased signaling enables pathway-selective drugs. Designer drugs: enhanced efficacy, reduced side effects. Applicable to GLP-1R, CGRP-R, PACAP receptors, and others.","whyItMatters":"Understanding that GLP-1 and CGRP receptors can be activated in pathway-selective ways opens doors to next-generation drugs that maximize therapeutic effects while minimizing side effects.","specificNumbers":"","methodology":"Narrative review of biased signaling pharmacology at class B GPCRs, covering approved therapeutics and drug development.","limitations":"Narrative review. Biased signaling measurement is complex. Translation from in vitro bias to clinical outcomes is uncertain. Few biased drugs have reached clinical testing."},{"rthcId":"RPEP-13780","title":"Use of Glucagon-Like Peptide-1 (GLP-1) Agonists in Modulating Preexisting Dermatologic Disease: A Systematic Review.","authors":"Tassavor, Bryan; Al Salem, Sultan","year":2025,"journal":"Cureus, 17(9), e93282","doi":"10.7759/cureus.93282","pmid":"41020015","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Improved conditions: psoriasis, HS, HAIR-AN syndrome, Hailey-Hailey, acne keloidalis, folliculitis decalvans, androgenic alopecia, localized scleroderma. Mechanisms: immunologic, metabolic, barrier-modulating. Evidence: controlled trials to case reports.","whyItMatters":"Many skin diseases lack effective treatments. Discovering that GLP-1 drugs—already taken by millions—improve diverse skin conditions opens new treatment avenues for dermatologists.","specificNumbers":"","methodology":"Systematic review of literature linking GLP-1RA use to improvement of preexisting dermatologic conditions.","limitations":"Systematic review with varying evidence quality. Most evidence from small studies or case reports. Cannot determine optimal dosing for skin conditions. May reflect publication bias."},{"rthcId":"RPEP-13781","title":"Intraductal Papillary Mucinous Neoplasms and GLP-1 Receptor Agonists: Navigating Therapeutic Uncertainty in Diabetes Management.","authors":"Tassone, Francesco; Saraceno, Giovanna","year":2025,"journal":"Biomedicines, 13(10)","doi":"10.3390/biomedicines13102326","pmid":"41153613","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1RAs: first-line T2DM therapy. IPMNs: premalignant pancreatic cysts. Unknown risk: GLP-1 pancreatotrophic effects on IPMN progression. Growing clinical dilemma. No specific studies available. Evidence-based guidelines needed.","whyItMatters":"Incidental IPMN discovery is increasing. Diabetes clinicians need guidance on whether GLP-1 drugs are safe for these patients or risk accelerating progression to pancreatic cancer.","specificNumbers":"","methodology":"Clinical perspective/opinion article addressing GLP-1 safety in IPMN patients.","limitations":"Opinion/perspective article with no original data. Theoretical risk based on mechanism, not demonstrated in studies. IPMNs are often benign."},{"rthcId":"RPEP-13782","title":"Liraglutide in the management of obesity: real world data (Portugal).","authors":"Tavares Bello, Carlos; Redondo Carvalho, Inês; Martins, Anabela; Martins, Ana F; Wessling, Ana; Macedo, Daniel; Martins, Diana; Fernandes, Carlos; Sobral DO Rosário, Francisco","year":2025,"journal":"Minerva endocrinology, 50(4), 371-376","doi":"10.23736/S2724-6507.24.04161-7","pmid":"39012306","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Liraglutide: mean 7.9% TBWL at 18 months. Metabolic improvements. Lower than clinical trial efficacy (8-12%). Portuguese real-world cohort. >50% population overweight/obese in Portugal.","whyItMatters":"Real-world data from Southern European populations is scarce. This Portuguese study confirms liraglutide effectiveness outside clinical trials while honestly reporting the efficacy gap between trial and practice settings.","specificNumbers":"","methodology":"Real-world observational study from Portuguese clinical practice.","limitations":"Observational. Real-world adherence lower than trials. Portuguese-specific. Specific weight loss numbers limited by abstract length. Comparator arm unknown."},{"rthcId":"RPEP-13783","title":"Immunological effects of GLP-1 analogs on female reproduction: Therapeutic perspectives for infertility and recurrent pregnancy loss.","authors":"Tavares, Ana Clara Muniz; Martins, Maria Yzadora Moura; de Souza, Giselle Ferreira; Lima, Eduarda Maia; Rocha, Camila Alves; de Souza, Larissa Cruz; Simões, Júlia Machado Luz; de Araújo, Nicole Oliveira; Cavalcante, Marcelo Borges","year":2025,"journal":"Journal of reproductive immunology, 169, 104538","doi":"10.1016/j.jri.2025.104538","pmid":"40359784","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1RAs improve fertility through: macrophage M2 polarization, ↓pro-inflammatory cytokines, ↑Treg activity, improved vascularization, ↓oxidative stress. Weight loss enhances insulin sensitivity and endocrine balance. Contraindicated during pregnancy. Preconception protocols promising.","whyItMatters":"Obesity-related infertility affects millions of women. Understanding that GLP-1 drugs improve fertility through immune mechanisms—not just weight loss—provides rationale for preconception GLP-1 therapy.","specificNumbers":"","methodology":"Narrative review of GLP-1RA immunological and metabolic effects relevant to reproduction.","limitations":"Review format. No clinical trials of GLP-1 drugs specifically for infertility. Pregnancy contraindication limits clinical translation. Immune mechanisms extrapolated from non-reproductive studies."},{"rthcId":"RPEP-13784","title":"Diverticular Stricture and Hepatic Abscess Formation During Tirzepatide Therapy for Obesity.","authors":"Taylor, Bethany; Farley-Hills, Edward; Yang, Wah; Pouwels, Sjaak; Whiteley, Graham; Wilkinson, Danielle; Agarwal, Anurag; Al-Ardah, Mahmoud; Beamish, Andrew; Hammoda, Mohammed; Hoffmann, Rebecca V; Ahmed, Ahmed; Ahmad, Suhaib","year":2025,"journal":"Cureus, 17(11), e96564","doi":"10.7759/cureus.96564","pmid":"41393655","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Age 53; pre-existing asymptomatic diverticular disease. Tirzepatide → 25 kg rapid weight loss → sigmoid stricture, obstructive diverticulitis, hepatic abscesses, severe sepsis, multi-organ dysfunction. Proposed: ↓colonic motility, altered bile, microbiota changes, bacterial translocation.","whyItMatters":"Diverticular disease is extremely common (>50% by age 60). If GLP-1 drugs can exacerbate it through motility effects, this represents a significant safety consideration for a large patient population.","specificNumbers":"","methodology":"Single case report with imaging and clinical documentation.","limitations":"Single case. Diverticulitis could be coincidental. Pre-existing diverticular disease may have progressed independently. Cannot establish causation."},{"rthcId":"RPEP-13785","title":"Body weight reduction in women treated with tirzepatide by reproductive stage: a post hoc analysis from the SURMOUNT program.","authors":"Tchang, Beverly G; Mihai, Andreea Ciudin; Stefanski, Adam; García-Pérez, Luis-Emilio; Mojdami, Donna; Jouravskaya, Irina; Gurbuz, Sirel; Taylor, Rebecca; Karanikas, Chrisanthi A; Dunn, Julia P","year":2025,"journal":"Obesity (Silver Spring, Md.), 33(5), 851-860","doi":"10.1002/oby.24254","pmid":"40074721","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"SURMOUNT-1 tirzepatide vs placebo: premenopause -26% vs -2%, perimenopause -23% vs -3%, postmenopause -23% vs -3% (all p significant). Significant WC and WHtR improvements. ~50% with baseline BMI ≥40 reached WHtR ≤0.49. Consistent across SURMOUNT-3 and -4.","whyItMatters":"Women gain weight and redistribute fat during menopause with limited options. Demonstrating tirzepatide works equally well regardless of menopausal status provides confidence for prescribers.","specificNumbers":"","methodology":"Post hoc analysis of 3 SURMOUNT RCTs. Women retrospectively categorized by reproductive stage. Tirzepatide 15 mg or MTD vs placebo. Body weight, WC, WHtR at end of study treatment.","limitations":"Post hoc analysis (not pre-specified). Retrospective menopause categorization. Cannot determine if hormonal status affects drug mechanism. SURMOUNT excluded T2DM (SURMOUNT-1,3,4)."},{"rthcId":"RPEP-13786","title":"Effect of semaglutide 2.4 mg on use of antihypertensive and lipid-lowering treatment in five randomized controlled STEP trials.","authors":"Tchang, Beverly G; Knight, Michael G; Adelborg, Kasper; Clements, Jennifer N; Iversen, Aske Thorn; Traina, Andrea","year":2025,"journal":"Obesity (Silver Spring, Md.), 33(2), 267-277","doi":"10.1002/oby.24202","pmid":"39756397","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide 2.4 mg vs placebo: more treatment intensity reduction + more treatment discontinuation for both antihypertensives and lipid-lowering drugs. Less treatment intensification. Greater weight loss correlated with medication changes. Two pooled populations: with and without T2DM.","whyItMatters":"Polypharmacy is a major problem in cardiometabolic disease. Demonstrating that semaglutide reduces medication burden—not just weight and metabolic parameters—has practical implications for patients taking multiple pills daily.","specificNumbers":"","methodology":"Post hoc analysis of pooled STEP 1, 3, 6, 8 (overweight/obesity) and STEP 2, 6 (overweight/obesity + T2DM). Antihypertensive and lipid-lowering medication changes from randomization to end of treatment.","limitations":"Post hoc analysis. Treatment changes were clinician-driven (not standardized). Cannot determine if medication changes were appropriate or sufficient. Pooled heterogeneous trial populations."},{"rthcId":"RPEP-13787","title":"Semaglutide effects on energy balance are mediated by Adcyap1+ neurons in the dorsal vagal complex.","authors":"Teixidor-Deulofeu, Júlia; Blid Sköldheden, Sebastian; Font-Gironès, Ferran; Feješ, Andrej; Ruud, Johan; Engström Ruud, Linda","year":2025,"journal":"Cell metabolism, 37(7), 1530-1546.e6","doi":"10.1016/j.cmet.2025.04.018","pmid":"40409256","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide activates AP/NTS Adcyap1+ neurons. Reactivation mimics drug effects (↓food intake, ↓weight, ↑fat utilization, CTA). Ablation reverses drug effects in lean + obese mice. Adcyap1+ neurons: promote fat > lean mass loss. Modest CTA contribution. AP GLP-1R neurons → NTS Adcyap1+ neurons → downstream satiety.","whyItMatters":"Understanding the exact neurons mediating semaglutide's effects enables design of next-generation drugs that selectively activate these neurons—maximizing fat loss while minimizing muscle loss and nausea.","specificNumbers":"","methodology":"Semaglutide-responsive neuron mapping. Chemogenetic reactivation (DREADD). Adcyap1+ neuron ablation. Lean and DIO mice. Body composition analysis. Conditioned taste aversion.","limitations":"Mouse study. Ablation is permanent—does not model reversible drug effects. Adcyap1 expression identifies but may not fully define the critical population. Human brainstem circuits may differ."},{"rthcId":"RPEP-13788","title":"GLP-1 Agonists and Cardiovascular Risk Markers in U.S. Adults: National Health and Nutrition Examination Survey (NHANES) 2011-2018.","authors":"Telakeng Tekengne, B Oneill; Eke, Catherine Ijeoma; Cumaaran, Christina; Ozigbo, Adaobi A; Okoyeuzu, Chinechem A; Okhagbuzo, Inemialu M; Sadiq-Onilenla, Rasheedat A; Okobi, Okelue E","year":2025,"journal":"Cureus, 17(9), e91722","doi":"10.7759/cureus.91722","pmid":"41058804","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"NHANES 2011-2018: GLP-1RA users showed improved cardiovascular risk markers vs non-users. Population-level US data. Supports cardiometabolic benefits of GLP-1 drugs.","whyItMatters":"Population-level data from NHANES provides a nationally representative view of GLP-1 drug effects—complementing clinical trials with real-world US diversity.","specificNumbers":"","methodology":"Cross-sectional analysis of NHANES 2011-2018 data. Cardiovascular risk marker comparison between GLP-1RA users and non-users.","limitations":"Cross-sectional design. Cannot establish causation. NHANES sampling methods. Self-reported medication use."},{"rthcId":"RPEP-13789","title":"Gut neuropeptide involvement in Parkinson's disease.","authors":"Templeton, Hayley N; Tobet, Stuart A; Schwerdtfeger, Luke A","year":2025,"journal":"American journal of physiology. Gastrointestinal and liver physiology, 328(6), G716-G733","doi":"10.1152/ajpgi.00383.2024","pmid":"40279198","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"7 dysregulated gut neuropeptides in PD: VIP, NPY, CGRP, ghrelin, CCK, GLP-1, substance P. GI symptoms precede motor symptoms by up to 20 years. α-Synuclein aggregates in GI tract. Gut neuropeptides modulate: barrier function, immune response, gut-brain signaling. Underexplored research area.","whyItMatters":"PD may begin in the gut years before brain symptoms. Understanding how gut neuropeptides contribute to disease initiation and progression could enable early detection and intervention.","specificNumbers":"","methodology":"Narrative review of gut neuropeptide roles in PD pathogenesis, covering microbial metabolite and immune influences on neuropeptide signaling.","limitations":"Narrative review. Mostly animal model evidence. Causation vs correlation unclear. Human gut neuropeptide data in PD limited."},{"rthcId":"RPEP-13790","title":"Oral semaglutide: an innovative paradigm in the management of cardiovascular risk in patients with Type 2 diabetes.","authors":"Temporelli, Pier Luigi","year":2025,"journal":"European heart journal supplements : journal of the European Society of Cardiology, 27(Suppl 1), i1-i5","doi":"10.1093/eurheartjsupp/suae086","pmid":"39980783","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Oral semaglutide: equivalent CV benefits to injectable. MACE reduction demonstrated. Weight loss + glycemic control. Tablet convenience improves access/adherence. T2DM + CVD risk management.","whyItMatters":"Injectable administration is a major barrier to GLP-1 drug adoption. Oral semaglutide removes this barrier while maintaining cardiovascular protection—potentially reaching millions more patients.","specificNumbers":"","methodology":"Narrative review of oral semaglutide clinical evidence for cardiovascular risk management.","limitations":"Narrative review. Oral semaglutide has dosing requirements (empty stomach, water restrictions) that may limit adherence. Head-to-head oral vs injectable CV outcome data is indirect."},{"rthcId":"RPEP-13791","title":"AAV-mediated gene therapy for focal epilepsy by expressing neuropeptide Y and Y2 receptor in rodent and non-human primate hippocampus.","authors":"Terzic, Barbara; Melin, Esbjörn; Fagergren, Pernilla; Dobry, David; Cattaneo, Stefano; Giupponi, Iris; Bettegazzi, Barbara; Simonato, Michele; Agerman, Karin; Kokaia, Merab; Moon, Lawrence; Ramsburg, Elizabeth","year":2025,"journal":"Molecular therapy : the journal of the American Society of Gene Therapy, 33(9), 4239-4258","doi":"10.1016/j.ymthe.2025.06.019","pmid":"40517292","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"SPK100.NPY-Y2R: ↓neuronal activity in cultures + slices. ↓Seizure progression/duration (rat kindling). ↓Spontaneous seizures (genetic mouse model). MRI-guided delivery → successful baboon hippocampus transduction. No adverse events. Non-human primate step completed.","whyItMatters":"30% of epilepsy patients resist all current drugs. NPY gene therapy could provide lasting seizure control from a single treatment, and successful baboon delivery brings it closer to human trials.","specificNumbers":"","methodology":"In vitro: rat cortical cultures, mouse hippocampal slices. In vivo: rat rapid kindling, synapsin triple KO mice spontaneous seizures. Non-human primate: MRI-guided CED to baboon hippocampus.","limitations":"Rodent models. Baboon delivery confirmed but no seizure testing in primates. Long-term NPY expression durability unknown. Neurosurgical delivery carries inherent risks."},{"rthcId":"RPEP-13792","title":"From Glycemic Control to Gut Telescoping: Intussusception in a Patient on a Glucagon-Like Peptide-1 Receptor Agonist.","authors":"Thakkar, Bianca; Nguyen, Minh Thu T; Hagen, Rachael; Parikh, Neil","year":2025,"journal":"ACG case reports journal, 12(5), e01679","doi":"10.14309/crj.0000000000001679","pmid":"40291604","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Age 32; semaglutide user. Transient small bowel intussusception on CT enterography (incidental finding). No obstruction or lead point. Resolved without intervention. Proposed mechanism: GLP-1-induced altered motility.","whyItMatters":"While adult intussusception is rare, GLP-1 drugs' profound motility effects could create conditions favoring this complication. As millions take these drugs, even rare complications become clinically relevant.","specificNumbers":"","methodology":"Single case report with CT enterography imaging documentation.","limitations":"Single case. Intussusception could be coincidental. No rechallenge. Adult intussusception often has other causes. Incidental finding during anemia workup."},{"rthcId":"RPEP-13793","title":"Deciphering the role of neuropeptides as biomarkers for early diagnosis of Parkinson's disease.","authors":"Thakur, Jhanvi; Godad, Angel","year":2025,"journal":"Life sciences, 363, 123376","doi":"10.1016/j.lfs.2025.123376","pmid":"39793854","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"5 neuropeptide biomarkers: α-synuclein, substance P, neurotensin, NPY, somatostatin. Measurable in: CSF, blood, saliva, tears, urine. Levels differ in PD. Correlate with severity. Distinguish PD from other conditions. ELISA detection.","whyItMatters":"PD is diagnosed too late—typically after 50-80% of dopamine neurons are already lost. Neuropeptide biomarkers in easily accessible fluids (blood, saliva) could detect PD years earlier, enabling neuroprotective intervention.","specificNumbers":"","methodology":"Narrative review of neuropeptide biomarker potential for early PD diagnosis.","limitations":"Review format. Individual studies small. Neuropeptide levels overlap between PD and controls. No single biomarker is sufficient. Multi-marker panels likely needed."},{"rthcId":"RPEP-13794","title":"A hydrophobic loop of the spider-venom peptide Tl1a drives activity at NaV1.8.","authors":"Thapa, Ashvriya; Tran, Hue; Ragnarsson, Lotten; Keramidas, Angelo; Herzig, Volker; Brinkwirth, Nina; Deuis, Jennifer R; Vetter, Irina","year":2025,"journal":"European journal of pharmacology, 1001, 177751","doi":"10.1016/j.ejphar.2025.177751","pmid":"40414593","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tl1a: 36 amino acids from T. longicolli. NaV1.8 IC50=210 nM. 8x selective over NaV1.4 (1769 nM), NaV1.1 (2201 nM). 6x over NaV1.7 (1278 nM). Similar at NaV1.5 (282 nM), KV2.1 (156 nM). Loop 4 hydrophobicity critical. Domain IV S3-S4 interaction site.","whyItMatters":"NaV1.8 is the target of the recently approved pain drug suzetrigine. Understanding how venom peptides interact with NaV1.8 provides templates for designing more selective pain drugs.","specificNumbers":"","methodology":"Solid-phase peptide synthesis. Automated whole-cell patch-clamp electrophysiology. Multiple NaV and KV channel subtypes. Loop 4 analogue structure-activity studies.","limitations":"In vitro electrophysiology only. NaV1.5 (cardiac) potency raises safety concerns. No pain model testing. Loop 4 modifications reduced NaV1.8 activity rather than improving it."},{"rthcId":"RPEP-13795","title":"Glucagon-Like Peptide-1 Agonist Use in Adults With Congenital Heart Disease: Effect, Safety, and Outcomes.","authors":"Thapa, Rashmi; Lara-Breitinger, Kyla M; Lopez-Jimenez, Francisco; Shama, Nishat; Egbe, Alexander C; Miranda, William R; Connolly, Heidi M; Jain, C Charles; Jokhadar, Maan; Kosec, Angela M; Alm, Svea; Burchill, Luke J","year":2025,"journal":"JACC. Advances, 4(4), 101674","doi":"10.1016/j.jacadv.2025.101674","pmid":"40132346","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"70 ACHD patients; 85.7% moderate/severe complexity. >5% weight loss: 42.9%. BMI≥35: 66.7% achieved >5% loss (p=0.027). Younger age: better response (p=0.014). HbA1c: -0.6%. GI side effects: 20%. Discontinuation: 11.4%. NYHA + eGFR: stable. Mean 21 months.","whyItMatters":"Adults with congenital heart disease have unique physiological vulnerabilities. Demonstrating GLP-1 drug safety in this population—including those with severe heart defects—fills a critical evidence gap.","specificNumbers":"","methodology":"Retrospective cohort at Mayo Clinic (Jan 2013-Jan 2024). 70 ACHD patients on semaglutide or liraglutide. Weight loss, NYHA class, HbA1c, eGFR, safety endpoints.","limitations":"Retrospective. Small sample (70). Single center. No control group. Mixed GLP-1 drugs. Weight loss response lower than general population."},{"rthcId":"RPEP-13796","title":"Incidence of GLP-1 receptor agonist use by women of reproductive age attending general practices in Australia, 2011-2022: a retrospective open cohort study.","authors":"Thapaliya, Kailash; Sweeting, Arianne; Black, Kirsten I; Poprzeczny, Amanda; Mazza, Danielle; Grzeskowiak, Luke E","year":2025,"journal":"The Medical journal of Australia, 223(7), 365-371","doi":"10.5694/mja2.70026","pmid":"40888243","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"1.6M women aged 18-49. GLP-1 prescribing: 0 → 14.9/1,000 (non-T2DM) by 2022. 90.5% of 2022 prescriptions: non-diabetic. Contraception documented: only 21.2%. Pregnancies within 6 months: 232/10,781. T2DM prescribing: 13.0 → 88.5/1,000.","whyItMatters":"GLP-1 drugs are contraindicated in pregnancy due to insufficient safety data. The finding that <25% of reproductive-age women have contraception at treatment initiation, with hundreds of pregnancies occurring, represents a patient safety crisis.","specificNumbers":"","methodology":"Retrospective open cohort study. MedicineInsight general practice data (1.6M women, 2011-2022). Age-standardized incidence. Contraception overlap analysis.","limitations":"General practice data may miss specialist prescribing. Contraception may be underrecorded. Pregnancy outcomes not detailed. Australian population."},{"rthcId":"RPEP-13797","title":"Semaglutide in heart failure and atherosclerotic cardiovascular disease: the current state-of-the-art.","authors":"Theodorakis, Nikolaos; Kreouzi, Magdalini; Nikolaou, Maria","year":2025,"journal":"Heart failure reviews, 30(4), 801-816","doi":"10.1007/s10741-025-10506-1","pmid":"40163257","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"ASCVD: MACE reduction in T2DM + non-T2DM. HFpEF: improved symptoms, function, NPs, echo, ↓HF hospitalization. SELECT HF subanalysis: ↓CV mortality + HF hospitalization. FLOW: renal + CV benefits in diabetic nephropathy independent of BMI. Evidence gaps: HF without ASCVD, non-obese HF.","whyItMatters":"This is the most comprehensive single-source synthesis of semaglutide cardiovascular evidence, providing clinicians with a complete picture for prescribing decisions across cardiorenal diseases.","specificNumbers":"","methodology":"State-of-the-art narrative review of semaglutide cardiovascular and renal clinical trial evidence.","limitations":"Review format. Dedicated HF trials without ASCVD criteria still needed. Non-obese HF patients not adequately studied. Long-term mortality data limited for HFpEF."},{"rthcId":"RPEP-13798","title":"The Effect of Fremanezumab on Pain in Patients with Complex Regional Pain Syndrome: Study Protocol of a Randomized, Double-Blind, Proof-of-Concept, Placebo-Controlled Trial.","authors":"Thiyagarajah, Abarajitha; Terkelsen, Astrid Juhl; Birklein, Frank; Finnerup, Nanna Brix; Gylfadottir, Sandra Sif","year":2025,"journal":"Brain sciences, 15(5)","doi":"10.3390/brainsci15050468","pmid":"40426639","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"60 patients; CRPS 3-36 months duration; fremanezumab 225 mg vs placebo SC; 8 weeks; primary: pain intensity change; secondary: pain relief, clinical signs, CGRP biomarker prediction; proof-of-concept design.","whyItMatters":"CRPS has no effective treatment and can cause lifelong disability. CGRP-driven neurogenic inflammation is a key pathophysiological mechanism, making anti-CGRP antibodies a rational therapeutic approach.","specificNumbers":"","methodology":"Randomized, double-blind, placebo-controlled, proof-of-concept trial. 60 adult CRPS patients. 1:1 randomization. 8-week treatment. CGRP biomarker analysis.","limitations":"Protocol paper—no results yet. Small sample (60). Short duration (8 weeks). CRPS is heterogeneous. Proof-of-concept, not definitive."},{"rthcId":"RPEP-13799","title":"Association between dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists and COVID-19 infection and adverse outcomes: a cohort study.","authors":"Thompson, Wade; Yu, Bing; Porter, Joan; Fang, Jiming; Ferreira-Legere, Laura E; Austin, Peter C; Jackevicius, Cynthia A; Ross, Heather; Lee, Douglas S; Weisman, Alanna; Farkouh, Michael E; Gershon, Andrea S; Atzema, Clare L; Kwong, Jeffrey C; Ha, Andrew; Džavík, Vladimír; Udell, Jacob A","year":2025,"journal":"BMJ open diabetes research & care, 13(4)","doi":"10.1136/bmjdrc-2024-004677","pmid":"40780839","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"COVID-19 infection: RR 0.99 (NS). Hospitalization: RR 0.79 (p<0.001), RD -6.72%. Major CV events: RR 0.73 (borderline p=0.05). 26,485 DPP4i/GLP-1RA vs 14,487 SGLT2i/SU. Age ≥66. 2020-2021.","whyItMatters":"COVID-19 disproportionately affects diabetic patients. Finding that incretin-based drugs reduce severe outcomes (hospitalization) suggests their anti-inflammatory properties provide protection during acute illness.","specificNumbers":"","methodology":"Population-based cohort study. Ontario, Canada. ≥66 years with T2DM on metformin + COVID-19 tested (Jan 2020-Jul 2021). Weighted risk differences and relative risks.","limitations":"91% were DPP4i users (not GLP-1RA)—effects may be primarily DPP4i-driven. Observational. 2020-2021 pandemic era (pre-vaccination for many). Older Canadian population."},{"rthcId":"RPEP-13800","title":"Real-world evidence on the utilization, clinical and comparative effectiveness, and adverse effects of newer GLP-1RA-based weight-loss therapies.","authors":"Thomsen, Reimar W; Mailhac, Aurélie; Løhde, Julie B; Pottegård, Anton","year":2025,"journal":"Diabetes, obesity & metabolism, 27 Suppl 2(Suppl 2), 66-88","doi":"10.1111/dom.16364","pmid":"40196933","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Real-world: meaningful weight loss but below trial efficacy. Barriers: adherence, drug shortages, cost, insurance coverage. Disparities: socioeconomic, racial/ethnic in prescribing. AEs: consistent with trials (GI predominant). Need: systemic solutions for sustained access.","whyItMatters":"Understanding the gap between trial and real-world GLP-1 drug performance—and the barriers causing it—is essential for public health planning as these drugs scale to millions of users.","specificNumbers":"","methodology":"Narrative review of published real-world GLP-1RA evidence for obesity.","limitations":"Narrative review. Real-world evidence is heterogeneous. Most data from Western countries. Rapidly evolving landscape."},{"rthcId":"RPEP-13801","title":"The NLRP3 inhibitor NT-0796 enhances and sustains GLP-1R agonist-mediated weight loss in a murine diet-induced obesity model.","authors":"Thornton, Peter; Reader, Valérie; Digby, Zsofia; Doedens, John; Lindsay, Nicola; Clarke, Nicholas; Watt, Alan P","year":2025,"journal":"Obesity (Silver Spring, Md.), 33(7), 1309-1321","doi":"10.1002/oby.24305","pmid":"40304241","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"NT-0796 + low-dose semaglutide > either monotherapy for weight loss. NT-0796 monotherapy sharply limited weight regain post-semaglutide. Normalized hypothalamic astrogliosis + peripheral inflammation. Enhanced effect with PUFA diet. NLRP3 inhibition: effective weight loss strategy alone.","whyItMatters":"Weight regain after stopping GLP-1 drugs is the Achilles heel of obesity pharmacotherapy. If anti-inflammatory drugs can prevent rebound, combination therapy could provide more sustainable weight loss.","specificNumbers":"","methodology":"DIO mice on HFD or PUFA diet. Semaglutide + NT-0796 combination. Body weight, food intake, peripheral inflammation, hypothalamic GFAP assessment.","limitations":"Mouse study. NT-0796 not yet in clinical trials for obesity. Low-dose semaglutide (not clinical dose). Short-term study. NLRP3 inhibition systemic effects unknown."},{"rthcId":"RPEP-13802","title":"Is Bariatric Surgery at Risk Due to Semaglutide?","authors":"Tian, Jane; Bhatia, Shubham; Sneed, Christina; Kiarie, Patrick; Fuchs, Mikayla; Miele, Andrew; Shah, Darshak; Khan, Noman; Louis, Martine A","year":2025,"journal":"Journal of metabolic and bariatric surgery, 14(3), 202-209","doi":"10.17476/jmbs.2025.14.3.202","pmid":"41568129","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide: effective but does not replace bariatric surgery for severe obesity. Complementary roles: pre-op weight loss, post-op regain rescue, weight maintenance. Surgery: still superior for severe obesity, diabetes remission, mechanical benefits.","whyItMatters":"Clarifying that semaglutide and surgery serve complementary rather than competitive roles helps clinicians and patients make informed treatment decisions.","specificNumbers":"","methodology":"Perspective/opinion article on semaglutide vs bariatric surgery roles.","limitations":"Opinion piece. Does not include primary data. Perspective may be influenced by surgical specialty viewpoint."},{"rthcId":"RPEP-13803","title":"Comparative evaluation of dulaglutide alone vs. dulaglutide combined with probiotics on cardiovascular risk factors in T2DM.","authors":"Tian, Jinxia; Yang, Yanfei; Yu, Zijuan; Gao, Yang; Zong, Xiaochun; Wu, Qiaojuan; Su, Haiyan; Cao, Wenjuan; Xu, Dandan","year":2025,"journal":"Hormones (Athens, Greece), 24(3), 643-650","doi":"10.1007/s42000-025-00649-z","pmid":"40214965","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Combo vs dulaglutide alone: HbA1c -1.06% vs -0.35% (p=0.028). FPG more improved (p=0.010). TNF-α: -43.6% vs -33.3% (p<0.001). HOMA-β: +34.7% vs +23.1% (p=0.034). Lactobacillus: +2.1 vs +1.3 ×10⁶ CFU/g (p<0.001). New HTN: 0% vs 13.3% (p=0.038). New dyslipidemia: 0% vs 16.7% (p=0.020).","whyItMatters":"Probiotics are cheap, safe, and widely available. Showing they can triple the glucose-lowering effect of a GLP-1 drug while preventing cardiovascular complications is clinically transformative.","specificNumbers":"","methodology":"RCT. 60 overweight/obese T2DM patients (HbA1c 6.5-11%, BMI ≥24). Control: dulaglutide 1.5mg/week + placebo. Intervention: dulaglutide + Bifidobacterium longum (2×10⁹ CFU). 12 weeks.","limitations":"Small RCT (60 patients). Single probiotic strain. 12-week duration. Chinese population. No long-term follow-up. Mechanism via microbiome modulation assumed."},{"rthcId":"RPEP-13804","title":"Semaglutide administration protects cardiomyocytes in db/db mice via energetic improvement and mitochondrial quality control.","authors":"Tian, Meng-Yun; Yang, Ji-Qin; Hu, Jin-Chuan; Lu, Shan; Ji, Yong","year":2025,"journal":"Acta pharmacologica Sinica, 46(5), 1250-1261","doi":"10.1038/s41401-024-01448-9","pmid":"39856432","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide in db/db mice: ↑cardiac function; ↑AMPK + ULK1 phosphorylation; ↑[Ca²⁺]mito; ↑basal, max, and spare respiration (Seahorse); ↑ATP production; ↑Parkin + LC3 (mitophagy); improved mitochondrial morphology (TEM). Direct CM protection.","whyItMatters":"Diabetic cardiomyopathy is a leading cause of death in T2DM. Proving semaglutide directly protects heart cells through specific mitochondrial mechanisms—not just glucose control—supports its use as a cardioprotective drug.","specificNumbers":"","methodology":"db/db diabetic mice treated with semaglutide (200 μg/kg/d IP, 8 weeks). Cardiac function assessment. Seahorse metabolic analysis. Western blot (AMPK, ULK1, Parkin, LC3). TEM for mitochondrial morphology.","limitations":"Mouse model (db/db). IP injection (not typical clinical route). 8-week treatment. Single dose. In vitro Seahorse data may not fully represent in vivo conditions."},{"rthcId":"RPEP-13805","title":"Efficacy and safety of tirzepatide for weight loss in patients with obesity or type 2 diabetes: a systematic review and meta-analysis.","authors":"Tian, Qiru; Song, Yi; Deng, Yan; Lin, Shike","year":2025,"journal":"Frontiers in endocrinology, 16, 1593134","doi":"10.3389/fendo.2025.1593134","pmid":"40747302","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Dose-response: 5 mg ~5%; 10 mg ~11-15%; 15 mg ~15-22.7% weight loss. Consistent in obesity + T2DM. Phase 1-3 trials included. GI AEs main side effects. Dose-dependent tolerability profile.","whyItMatters":"Quantifying the exact dose-response relationship helps clinicians and patients set realistic expectations and choose the right dose based on weight loss goals and side effect tolerance.","specificNumbers":"","methodology":"Systematic review and meta-analysis of phase 1-3 tirzepatide trials. Dose-response analysis (5, 10, 15 mg). Weight loss and adverse event assessment.","limitations":"Meta-analysis of published trials. Individual patient data not available. Dose titration schedules varied. Long-term weight maintenance not assessed."},{"rthcId":"RPEP-13806","title":"GLP-1/GIP dual agonist tirzepatide alleviates mice model of Parkinson's disease by promoting mitochondrial homeostasis.","authors":"Tian, Ruixue; Liu, Kexin; Lai, Hurong; Liao, Caifeng; Li, Jian; Tu, Huaijun","year":2025,"journal":"International immunopharmacology, 165, 115443","doi":"10.1016/j.intimp.2025.115443","pmid":"40886502","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP1R + GIPR downregulated in PD patient neurons. Tirzepatide (1/3 dose) = semaglutide for TH preservation. ↓Drp1 (pathological fission). ↑Pink1/Parkin/p62 (mitophagy). ↑ATP. Improved mitochondrial ultrastructure. Validated by Drp1 inhibitor + mitophagy activator.","whyItMatters":"Finding that tirzepatide works at one-third the dose of semaglutide for PD suggests the GIP receptor component provides additional neuroprotection, potentially making dual agonists preferred over mono GLP-1 drugs for neurodegeneration.","specificNumbers":"","methodology":"GSE238129 transcriptomic analysis (PD patients). MPTP-induced subacute PD mice. Tirzepatide, semaglutide, levodopa comparison. TEM, Western blot, IHC. Drp1 inhibitor + mitophagy activator validation. SY5Y cell CQ + 3-MA validation.","limitations":"MPTP model (acute toxin, not progressive PD). Mouse study. In vivo doses may not translate to human equivalents. Short treatment duration."},{"rthcId":"RPEP-13807","title":"GLP-1 Receptor Agonists Alleviate Diabetic Kidney Injury via β-Klotho-Mediated Ferroptosis Inhibition.","authors":"Tian, Shasha; Zhou, Saijun; Wu, Weixi; Lin, Yao; Wang, Tongdan; Sun, Haizhen; A-Ni-Wan, A-Shan-Jiang; Li, Yaru; Wang, Chongyang; Li, Xiaogang; Yu, Pei; Zhao, Yanjun","year":2025,"journal":"Advanced science (Weinheim, Baden-Wurttemberg, Germany), 12(4), e2409781","doi":"10.1002/advs.202409781","pmid":"39630101","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide → cAMP-PKA-CREB → ↑KLB (β-Klotho) → AMPK activation → ↓ferroptosis (↓iron, ↓fatty acid synthesis, ↑antioxidant). Result: ↓renal inflammation, ↓fibrosis. Validated in patients, animals, HK-2 cells. KLB identified by transcriptome sequencing.","whyItMatters":"DKD is the leading cause of end-stage kidney failure. Identifying the exact molecular pathway (cAMP→KLB→AMPK→anti-ferroptosis) by which semaglutide protects kidneys enables targeted therapeutic optimization.","specificNumbers":"","methodology":"Transcriptome sequencing for target identification. DKD patient samples, animal models, HK-2 kidney cells. cAMP-PKA-CREB pathway analysis. AMPK signaling. Ferroptosis markers (iron, lipid peroxidation, antioxidant).","limitations":"Complex pathway—causation at each step needs further validation. KLB upregulation mechanism via cAMP is novel and needs independent confirmation. HK-2 cells may not fully represent in vivo kidney tubules."},{"rthcId":"RPEP-13808","title":"GLP-1/GIP dual agonist tirzepatide normalizes diabetic nephropathy via PI3K/AKT mediated suppression of oxidative stress.","authors":"Tian, Yan; Tian, Ruixue; Juan, He; Guo, Yafan; Yan, Pan; Cheng, Yao; Li, Rongshan; Wang, Baodong","year":2025,"journal":"International immunopharmacology, 146, 113877","doi":"10.1016/j.intimp.2024.113877","pmid":"39700965","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tirzepatide 1/3 dose = semaglutide for: ↓glucose, ↓weight, ↓UACR. Insulin: could not restore UACR. RNA-seq: PI3K-AKT enriched. Tirzepatide: regulated oxidative stress via PI3K-AKT in podocytes. PI3K inhibitor: reversed antioxidative effect. DN treatment advantage over insulin.","whyItMatters":"Diabetic nephropathy leads to dialysis for millions. Tirzepatide achieving equal kidney protection at lower dose—where insulin fails for proteinuria—positions dual agonism as a superior approach for diabetic kidney disease.","specificNumbers":"","methodology":"DN mouse model. Tirzepatide, semaglutide, insulin comparison. RNA-seq of renal tissue. Mouse podocyte cell-5 (MPC5) high glucose experiments. PI3K inhibitor validation.","limitations":"Mouse model. RNA-seq pathway enrichment is associative. Single PI3K inhibitor used. Short treatment duration. Podocyte cells may not represent all kidney cell types."},{"rthcId":"RPEP-13809","title":"Semaglutide promotes the proliferation and osteogenic differentiation of bone-derived mesenchymal stem cells through activation of the Wnt/LRP5/β-catenin signaling pathway.","authors":"Tian, Yawei; Liu, Huiming; Bao, Xiaoxue; Li, Yukun","year":2025,"journal":"Frontiers in pharmacology, 16, 1539411","doi":"10.3389/fphar.2025.1539411","pmid":"40129942","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide → ↑BMSC proliferation, ↑migration, ↑ALP, ↑mineralization, ↑OCN, ↑RUNX2. RNA-seq → Wnt/LRP5/β-catenin pathway. DKK1 (Wnt inhibitor): partially reversed by semaglutide. LiCl (Wnt agonist) + semaglutide: synergistic osteogenic acceleration.","whyItMatters":"Diabetic osteoporosis is common and has few treatments that address both diabetes and bone loss. Semaglutide's ability to promote bone formation through Wnt signaling adds a skeletal benefit to its metabolic effects.","specificNumbers":"","methodology":"In vitro BMSC studies. CCK-8, flow cytometry, ALP/alizarin red staining, wound healing, Western blot, RT-PCR, immunofluorescence, RNA sequencing. DKK1 + LiCl pathway validation.","limitations":"In vitro only. BMSCs may respond differently in vivo. Dose translation unclear. Long-term bone effects in humans not studied. Wnt pathway has complex in vivo regulation."},{"rthcId":"RPEP-13810","title":"Thymosin alpha 1 alleviates inflammation and prevents infection in patients with severe acute pancreatitis through immune regulation: a systematic review and meta-analysis.","authors":"Tian, Yong; Yao, Jiaqi; Ma, Yihan; Zhang, Pengcheng; Zhou, Xiaofang; Xie, Wenjie; Tang, Wenfu","year":2025,"journal":"Frontiers in immunology, 16, 1571456","doi":"10.3389/fimmu.2025.1571456","pmid":"40599771","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"↑CD4+ T cells (MD=4.53, p<0.00001). ↑CD4/CD8 ratio (MD=0.42, p<0.00001). ↓CRP (low-dose): -30 mg/L (p<0.00001). ↓Infections: RR 0.56 (p=0.0005). Blood: RR 0.60. Abdominal: RR 0.38. ↓APACHE II: -1.52 (p<0.0001). Hospital stay: NS. 5 RCTs, 706 patients.","whyItMatters":"SAP has 20-40% mortality, largely from secondary infections due to immune suppression. Tα1's ability to restore immune function and prevent infections addresses a critical unmet need.","specificNumbers":"","methodology":"Meta-analysis of 5 RCTs from PubMed, Embase, WoS, Cochrane, CNKI. 706 SAP patients. Review Manager 5.3. Random/fixed effects. PROSPERO CRD42024570517.","limitations":"Only 5 RCTs available. Mostly Chinese studies. High-dose Tα1 did not reduce CRP (dose-response paradox). Hospital stay not reduced. Lung infection reduction NS."},{"rthcId":"RPEP-13811","title":"Modulation of metabolic syndrome components by oral semaglutide in hypothyroid-T2DM patients: a retrospective analysis.","authors":"Tilici, Dana-Mihaela; Costinescu, Ruxandra-Mihaela; Paun, Diana-Loreta; Paun, Sorin Constantin; Guja, Cristian","year":2025,"journal":"Journal of medicine and life, 18(12), 1094-1099","doi":"10.25122/jml-2025-0144","pmid":"41635458","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"HbA1c: -6.7% (p significant). BMI: significantly reduced. SBP and DBP: significantly reduced. Triglycerides: significantly reduced (p=0.002). HDL: increased. 51 patients; hypothyroid + T2DM; oral semaglutide 14 mg; 6 months.","whyItMatters":"Hypothyroid diabetic patients are often treatment-resistant due to compounded metabolic dysfunction. Showing oral semaglutide works in this complex population addresses a real clinical gap.","specificNumbers":"","methodology":"Single-center retrospective cohort. 51 adults with hypothyroidism + T2DM. Oral semaglutide 14 mg daily for 6 months. HbA1c, BMI, BP, lipid panel.","limitations":"Small retrospective study (51 patients). Single center. No control group. Levothyroxine interaction not fully explored. Short follow-up."},{"rthcId":"RPEP-13812","title":"Preservation of lean soft tissue during weight loss induced by GLP-1 and GLP-1/GIP receptor agonists: A case series.","authors":"Tinsley, Grant M; Nadolsky, Spencer","year":2025,"journal":"SAGE open medical case reports, 13, 2050313X251388724","doi":"10.1177/2050313X251388724","pmid":"41122508","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Case 1: -33% weight, -53.4% fat, -6.9% lean (8.7% of loss as lean). Case 2: -26.8% weight, -61.6% fat, +2.5% lean. Case 3: -13.2% weight, -46.9% fat, +5.8% lean. Exercise: 4-7d/week, RT 3-5d/week. Protein: 0.7-1.7 g/kg BW (1.6-2.3 g/kg FFM).","whyItMatters":"The muscle loss concern with GLP-1 drugs has been a major criticism. These cases demonstrate that with intentional exercise and protein, lean mass can be preserved or even gained—directly countering the \"Ozempic muscle\" concern.","specificNumbers":"","methodology":"Case series. 3 patients (2F, 1M; BMI 32.9-51.9). Semaglutide or tirzepatide. Body composition by DXA or BIA. Exercise and protein intake tracking.","limitations":"Only 3 patients. Self-selected motivated individuals. No control comparison. Different GLP-1 drugs and doses. Short case series."},{"rthcId":"RPEP-13813","title":"Association of GLP1-Receptor Agonists with Risk of Hepatocellular Carcinoma: A Retrospective Cohort Study.","authors":"Titus, Joane; Katukuri, Vinay; Boktor, Moheb; Mansi, Ishak A","year":2025,"journal":"Drug safety, 48(10), 1089-1101","doi":"10.1007/s40264-025-01558-1","pmid":"40587039","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1RA vs DPP4i: HCC OR 1.31 (1.11-1.56, p<0.001). >6 months use: increased risk. <6 months: OR 0.96 (NS). HCC: 302 (0.30%) GLP-1RA vs 230 (0.23%) DPP4i. 100,248 matched pairs. 133 PS variables.","whyItMatters":"This is the first large study finding a statistically significant HCC risk increase with GLP-1 drugs. While modest, it warrants monitoring given millions of users and expanding indications.","specificNumbers":"","methodology":"Retrospective PS-matched cohort from VHA (2006-2021). New-user active comparator design. 133-variable propensity score. 100,248 matched pairs. Secondary analysis by duration.","limitations":"Veterans population (predominantly male, older). DPP4i comparator may itself affect HCC risk. 133 PS variables cannot fully control confounding. HCC is rare. Duration analysis suggests confounding by indication (sicker patients use longer)."},{"rthcId":"RPEP-13814","title":"Changes in eating behavior and diet-related quality of life in individuals treated with tirzepatide for type 2 diabetes.","authors":"Toga-Sato, Shiori; Tosaki, Takahiro; Hodai, Yuichi; Kondo, Masaki; Miura-Yura, Emiri; Kato, Makoto; Morishita, Yoshiaki; Tsunekawa, Shin; Himeno, Tatsuhito; Kato, Yoshiro; Nakamura, Jiro; Kamiya, Hideki","year":2025,"journal":"Diabetology international, 16(4), 648-660","doi":"10.1007/s13340-025-00829-7","pmid":"41111575","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tirzepatide: significant changes in eating behavior at 3 months. Weight loss and HbA1c improvement. Diet-related QoL changes assessed. 60 T2DM outpatients.","whyItMatters":"GLP-1/GIP drugs fundamentally change how people relate to food. Understanding these behavioral changes helps clinicians provide holistic support during treatment.","specificNumbers":"","methodology":"Observational study of 60 T2DM outpatients on tirzepatide for 3 months. Eating behavior questionnaires. Body weight. HbA1c. Diet-related QoL assessment.","limitations":"Small study (60). Short follow-up (3 months). Single center. No control group. Diet QoL tools may not capture all relevant changes."},{"rthcId":"RPEP-13815","title":"Vertebral artery dissection in a patient with migraine treated with calcitonin gene-related peptide monoclonal antibody: a case report and FAERS database analysis.","authors":"Tokuyasu, Daiki; Imai, Shungo; Chen, Shih-Pin; Ihara, Keiko; Watanabe, Narumi; Izawa, Yoshikane; Nakahara, Jin; Hori, Satoko; Takizawa, Tsubasa","year":2025,"journal":"BMC neurology, 25(1), 1","doi":"10.1186/s12883-024-04009-z","pmid":"39748278","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"First case: vertebral artery dissection on anti-CGRP mAb. FAERS: CeAD signals for CGRP-blocking drugs detected. CGRP: vasodilatory → removal may ↓vascular protection. Migraine independently associated with CeAD risk.","whyItMatters":"CGRP protects blood vessels through vasodilation. Blocking it for migraine could theoretically increase arterial dissection risk—a rare but devastating event. With millions on anti-CGRP drugs, even rare vascular events are important.","specificNumbers":"","methodology":"Case report + FAERS database disproportionality analysis for CeAD with anti-CGRP drugs.","limitations":"Single case. Migraine itself causes CeAD risk (confounding). FAERS data is spontaneous reporting. Cannot establish causation."},{"rthcId":"RPEP-13816","title":"Pancreatic cancer-related diabetes and type 2 diabetes differ in multiple aspects of glucose homeostasis.","authors":"Toledo, Frederico G S; Li, Yisheng; Wang, Fuchenchu; Bellin, Melena D; Brand, Randall; Cusi, Kenneth; Fisher, William; Kudva, Yogish C; Park, Walter G; Saeed, Zeb I; Yadav, Dhiraj; Considine, Robert V; Graham, Sarah C; Andersen, Dana K; Serrano, Jose; Goodarzi, Mark O; Hart, Phil A","year":2025,"journal":"Diabetologia, 68(12), 2854-2866","doi":"10.1007/s00125-025-06543-y","pmid":"40991017","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"PDAC-DM vs T2DM: different GLP-1 and GIP responses; altered insulin/glucagon dynamics; distinct glucose homeostasis patterns; potential for earlier cancer detection if distinguished from T2DM.","whyItMatters":"Misdiagnosing pancreatic cancer-related diabetes as T2DM delays cancer detection. Finding distinct incretin response patterns could enable screening tools that identify PDAC-DM early.","specificNumbers":"","methodology":"Comparative study of glucose homeostasis parameters in PDAC-DM versus T2DM patients.","limitations":"Specific incretin differences not detailed in abstract preview. Sample sizes unclear. Distinguishing patterns may overlap significantly. Practical screening tool not yet developed."},{"rthcId":"RPEP-13817","title":"Real-World Weight Loss Among Patients Initiating Semaglutide 2.4 mg and Enrolled in WeGoTogether, a Digital Self-Support Application.","authors":"Toliver, Joshua C; Divino, Victoria; Ng, Carmen D; Wang, Julia","year":2025,"journal":"Advances in therapy, 42(10), 5010-5022","doi":"10.1007/s12325-025-03325-1","pmid":"40768192","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide 2.4 mg + digital self-support app (WeGoTogether). Real-world weight loss effectiveness. Long-term follow-up. Digital health engagement assessed.","whyItMatters":"Digital health tools could solve the adherence and behavioral support gaps that limit real-world GLP-1 drug effectiveness versus clinical trials.","specificNumbers":"","methodology":"Real-world study of semaglutide 2.4 mg users enrolled in WeGoTogether digital self-support application.","limitations":"Real-world observational. Self-selected digital app users. Cannot separate drug from app effects without control group."},{"rthcId":"RPEP-13818","title":"\"Next-in-class\" GLP-1R Danuglipron- and Lotiglipron-like Agonists: A Patent Review (2020-2024).","authors":"Tolkacheva, Elena V; Saliev, Alexandr Yu; Salakhov, Tagir L; Balakin, Konstantin V; Ivanov, Roman A; Chernyshov, Vladimir V","year":2025,"journal":"Current medicinal chemistry","doi":"10.2174/0109298673366258250710101146","pmid":"40873282","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"67 patents; 5,000+ compounds analyzed; 2021-2024. SAR: carboxyl groups → high activity; bioisosteres → better ADME; privileged fragments identified; heterocycle replacements viable; piperidine modifications promising. Clinical: danuglipron/lotiglipron had issues but spawned robust pipeline.","whyItMatters":"The injection barrier limits GLP-1 drug adoption. Identifying SAR trends from 5,000+ oral candidates accelerates the development of non-injectable alternatives that could reach billions more patients.","specificNumbers":"","methodology":"Patent review of Espacenet and Google Patents databases (Jan 2021-Jul 2024). SAR analysis of danuglipron- and lotiglipron-like agonists. 67 publications, 5,000+ compounds.","limitations":"Patent review—not clinical data. Most compounds are untested in humans. Complex GLP-1R signaling may limit small-molecule approaches. Biased signaling implications unknown."},{"rthcId":"RPEP-13819","title":"Neuropeptide Y receptors 1 and 2 as molecular targets in prostate and breast cancer therapy.","authors":"Tomić, Katarina; Kostevšek, Nina; Romeo, Sergio; Bassanini, Ivan","year":2025,"journal":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 187, 118117","doi":"10.1016/j.biopha.2025.118117","pmid":"40319656","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"NPY R1 and R2: overexpressed in multiple cancers. Breast cancer: significant tumor-normal difference (most promising target). Key NPY binding residues identified. Stability solutions: sequence mods, stapling, conjugation. Best use: combinatorial with chemotherapy for targeted delivery.","whyItMatters":"Cancer drug delivery remains a major challenge. NPY receptors on tumor cells could serve as \"addresses\" for targeted drug delivery, reducing side effects while increasing tumor drug concentrations.","specificNumbers":"","methodology":"Comprehensive narrative review of NPY receptor expression in cancers, NPY analog structure-activity, and therapeutic strategies.","limitations":"Review format. Most NPY targeting data is preclinical. Breast cancer is most promising but clinical trials are lacking. NPY analog stability in vivo remains challenging."},{"rthcId":"RPEP-13820","title":"The Potential of Using Glucagon-Like Peptide-1 Receptor Agonists in Sepsis.","authors":"Tomy, Noel; Shwartzman, Benjamin; Frishman, William H","year":2025,"journal":"Cardiology in review","doi":"10.1097/CRD.0000000000000998","pmid":"40745623","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Preclinical: GLP-1 agonists ↓inflammation, ↓oxidative stress, ↓mitochondrial dysfunction, preserved endothelial integrity. Animal: ↓organ damage, ↑survival. Clinical: ↓infection complications, ↓mortality. Mechanisms: anti-inflammatory + cardioprotective + neuroprotective.","whyItMatters":"Sepsis kills 11 million people annually with limited effective treatments. GLP-1 drugs' multi-organ protective properties could provide adjunctive therapy for this devastating condition.","specificNumbers":"","methodology":"Narrative review of preclinical and clinical evidence for GLP-1 agonists in sepsis.","limitations":"Mostly preclinical evidence. Clinical data is observational. Sepsis is heterogeneous. Optimal GLP-1 dosing for sepsis unknown. No prospective sepsis trials."},{"rthcId":"RPEP-13821","title":"The macrocyclic peptide rhesus theta defensin 1 activates interferon and antiviral pathways in human monocytes.","authors":"Tongaonkar, Prasad; Trinh, Katie K; Henley, Jill E; Sell, Philip J; Thakker, Vyoma; Ouellette, André J; Selsted, Michael E","year":2025,"journal":"Journal of leukocyte biology, 117(12)","doi":"10.1093/jleuko/qiaf150","pmid":"41139211","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"RTD-1 in human monocytes: ↑interferon and antiviral gene expression (RNA-seq). Mechanism: JAK-dependent STAT1 Y701 phosphorylation, IFNAR-dependent, NF-κB-independent. Antiviral: ↓VSV infection (THP-1), ↓SARS-CoV-2 spike pseudovirus (Vero E6), ↓authentic SARS-CoV-2 (Calu-3).","whyItMatters":"RTD-1 is unique: it is both anti-inflammatory (inhibits NF-κB) AND antiviral (activates interferon). This dual activity could be valuable for treating viral infections where inflammation itself is damaging, like COVID-19.","specificNumbers":"","methodology":"RNA-seq of RTD-1-treated human monocytes and THP-1 cells. STAT1 phosphorylation. ISRE reporter assays with JAK inhibitor and IFNAR blockade. Viral infection inhibition assays (VSV, SARS-CoV-2 pseudovirus, authentic SARS-CoV-2).","limitations":"In vitro studies. RTD-1 is from rhesus macaques (not human). Human theta defensins are pseudogenes. Bioavailability and delivery challenges. Antiviral potency not quantified."},{"rthcId":"RPEP-13822","title":"Neurobiological Mechanisms and Therapeutic Potential of Glucagon-like Peptide-1 Receptor Agonists in Binge Eating Disorder: A Narrative Review.","authors":"Tongta, Sujitra; Sungkaworn, Titiwat; Pathomthongtaweechai, Nutthapoom","year":2025,"journal":"International journal of molecular sciences, 26(22)","doi":"10.3390/ijms262210974","pmid":"41303457","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1R expressed in: hypothalamus (appetite) + mesolimbic circuits (reward). Preclinical: ↓food-seeking, ↓dopamine reward signaling, ↓compulsive eating. Clinical: semaglutide + liraglutide → ↓binge episodes, ↓cravings, ↑symptom scores. Dual mechanism: metabolic + reward pathways.","whyItMatters":"BED affects 3% of the population with very limited treatments. GLP-1 drugs' ability to modify compulsive eating through reward circuit modulation—not just appetite suppression—addresses the disorder's core pathology.","specificNumbers":"","methodology":"Narrative review of preclinical and clinical GLP-1RA evidence for BED (PubMed/MEDLINE through May 2025).","limitations":"Narrative review. Small clinical studies. Translating animal compulsive eating to human BED is challenging. Optimal dosing for BED unknown."},{"rthcId":"RPEP-13823","title":"Genetic variability in sodium-glucose cotransporter 2 and glucagon-like peptide 1 receptor effect on glycemic and pressure control in type 2 diabetes patients treated with SGLT2 inhibitors and GLP-1RA in the everyday clinical practice.","authors":"Tonin, Gašper; Goričar, Katja; Blagus, Tanja; Janež, Andrej; Dolžan, Vita; Klen, Jasna","year":2025,"journal":"Frontiers in endocrinology, 16, 1547920","doi":"10.3389/fendo.2025.1547920","pmid":"40692597","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP1R rs6923761 A allele (prevalent): significantly worse HbA1c response to GLP-1RA vs G allele (p=0.029, dominant model). Overall: all treatments improved HbA1c, weight, BP (p significant). 161 T2DM patients. Real-world clinical practice. SLC5A2 variant: tested for SGLT2i.","whyItMatters":"Knowing a patient's GLP1R genotype before prescribing could guide drug selection—patients with the A allele might benefit more from tirzepatide (dual mechanism) or alternative approaches.","specificNumbers":"","methodology":"Prospective interventional open-label cohort (DRKS00034478). 161 T2DM patients. GLP1R rs6923761, rs10305420, SLC5A2 rs9934336 genotyping by competitive allele-specific PCR. 3-6 month follow-up.","limitations":"Small sample (161). Single polymorphism significant. Open-label. 3-6 month follow-up. Single center. Clinical significance of the HbA1c difference not quantified."},{"rthcId":"RPEP-13824","title":"High Dose of Liraglutide Impairs Renal Function in Female Hypertensive Rats.","authors":"Tonon Firmino, Felipe; Peixoto, Pollyana; Batista, Thatiany Jardim; Escouto, Leonardo da Silva; Brasil, Girlandia Alexandre; Couto, Mariana Dos Reis; de Melo Júnior, Antonio Ferreira; Bissoli, Nazaré Souza","year":2025,"journal":"Journal of cardiovascular pharmacology, 85(2), 120-128","doi":"10.1097/FJC.0000000000001649","pmid":"39514188","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"High dose (0.6 mg/kg): ↑BUN, ↑BUN/Cr, ↑collagen deposition, aberrant ↑GFR, ↑nitrate, ↓nitrite, ↑urinary Na/K ratio. Low dose (0.06 mg/kg): ↓APOP (protective). Both: ↓weight, BP/glucose independent. Female SHR model, 30 days.","whyItMatters":"GLP-1 drugs are generally considered renoprotective. This study reveals a dose-dependent toxicity in hypertensive females that could have clinical implications for high-dose prescribing in this population.","specificNumbers":"","methodology":"Female SHR rats treated 30 days, 2x daily. Saline, low-dose (0.06 mg/kg), or high-dose (0.6 mg/kg) liraglutide. 24h volume monitoring. Renal tissue: nitrite/nitrate, APOP, collagen, Cr, U, Na, K.","limitations":"Rat model (SHR). Doses may not directly translate to human clinical doses. 30-day study. Female-only. Aberrant GFR increase mechanism not fully explained."},{"rthcId":"RPEP-13825","title":"Altered expressions of CGRP, SULT1A1, HMGB1, and HIF-1α in the trigeminal ganglion in medication overuse headache in female rats.","authors":"Topa, Elif Gulcicek Abbasoglu; Vuralli, Doga; Usta, Duygu Deniz; Calikusu, Aysen; Yigman, Zeynep; Bolay, Hayrunnisa","year":2025,"journal":"The journal of headache and pain, 26(1), 221","doi":"10.1186/s10194-025-02191-0","pmid":"41107721","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"↑CGRP neurons + protein. HMGB1: ↑cytoplasmic translocation (neurons + SGCs). HIF-1α: ↑nuclear localization (neurons + SGCs). SULT1A1: significantly ↓ (neurons only, not SGCs). Female rats. Piroxicam MOH model. First description of HMGB1/HIF-1α changes in MOH.","whyItMatters":"MOH affects 1-2% of the population. Understanding its molecular basis through CGRP, inflammation (HMGB1), hypoxia (HIF-1α), and detoxification (SULT1A1) reveals new therapeutic targets beyond simply stopping the offending medication.","specificNumbers":"","methodology":"Female Sprague Dawley rats. Oral piroxicam MOH induction. Periorbital mechanical thresholds + nociceptive behaviors (metestrus/diestrus phases). TG immunohistochemistry + Western blot for CGRP, HMGB1, HIF-1α, SULT1A1.","limitations":"Rat model. Female-only (relevant for female-predominant MOH). Single NSAID tested. Mechanisms are correlative. LPS/gut permeability role not clarified."},{"rthcId":"RPEP-13826","title":"The Risk of Vestibular Disorders with Semaglutide and Tirzepatide: Findings from a Large Real-World Cohort.","authors":"Toraih, Eman A; Alenezy, Awwad; Hussein, Mohammad H; Hashmat, Shahmeer; Mummadi, Saitej; Alrawili, Nawaf Farhan; Abdelmaksoud, Ahmed; Fawzy, Manal S","year":2025,"journal":"Biomedicines, 13(5)","doi":"10.3390/biomedicines13051049","pmid":"40426877","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide vestibular disorders: 0.12% (6m), 0.41% (3y) vs controls 0.03%, 0.16% (all p significant). Tirzepatide: increased risk but lower than semaglutide (p significant). 419,497 semaglutide + 77,259 tirzepatide users matched.","whyItMatters":"Vestibular disorders cause debilitating dizziness and imbalance. With nearly 500,000 semaglutide users studied, even a 0.41% 3-year risk means thousands of affected patients nationally.","specificNumbers":"","methodology":"Retrospective cohort from TriNetX (Nov 2024). Propensity score 1:1 matching. Semaglutide (419,497) and tirzepatide (77,259) vs matched controls. New-onset vestibular disorders at 6m, 1y, 3y.","limitations":"Retrospective TriNetX data. Vestibular disorder definitions may vary. Cannot determine mechanism. Weight loss itself could affect vestibular function."},{"rthcId":"RPEP-13827","title":"Liraglutide Treatment Reverses Unconventional Cellular Defects in Induced Pluripotent Stem Cell-Derived β-Cells Harboring a Partially Functional WFS1 Variant.","authors":"Torchio, Silvia; Siracusano, Gabriel; Cuozzo, Federica; Zamarian, Valentina; Pellegrini, Silvia; Manenti, Fabio; Bonfanti, Riccardo; Frontino, Giulio; Sordi, Valeria; Chimienti, Raniero; Piemonti, Lorenzo","year":2025,"journal":"Diabetes, 74(7), 1273-1288","doi":"10.2337/db24-0720","pmid":"40202504","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"WS1 iPSC β-cells: ↓insulin processing (proinsulin accumulation, ↓PC1/3), dysregulated Ca²⁺ (altered CACNA1D), ↓SNAP25, ↑autophagy, ↑cytokine-induced apoptosis. Liraglutide: normalized Ca²⁺, ↑insulin processing/secretion, ↓apoptosis. Mechanism: UPR modulation. c.316-1G>A and c.757A>T mutations.","whyItMatters":"Wolfram syndrome has no treatment. Demonstrating liraglutide rescues mutation-specific β-cell defects in patient-derived cells provides a strong rationale for personalized GLP-1 therapy in this devastating genetic disease.","specificNumbers":"","methodology":"Patient-derived iPSC β-cells (WFS1 c.316-1G>A/c.757A>T). Insulin processing, Ca²⁺ imaging, secretory function, autophagy, apoptosis assays. Liraglutide treatment. UPR analysis.","limitations":"In vitro iPSC model. Specific WFS1 mutations—may not apply to all WS1 variants. β-cell focus does not address WS1 neurological or optic features. Long-term effects unknown."},{"rthcId":"RPEP-13828","title":"High Salt Intake Affects Visceral Adipose Tissue Homeostasis: Beneficial Effects of GLP-1 Agonists.","authors":"Touceda, Vanessa; Cacciagiú, Leonardo; Moglie, Ignacio Barbani; Wiszniewski, Morena; Sanchez, Valeria; De Lucca, Romina C; Vidal, Agustina; Finocchietto, Paola; Friedman, Silvia; González, Germán E; Miksztowicz, Verónica","year":2025,"journal":"Biology, 14(9)","doi":"10.3390/biology14091171","pmid":"41007316","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"HSD (15 weeks): ↓body weight/VAT mass, ↓adipocyte size, ↑collagen, ↓vascular density, mitochondrial stress, ↑oxidative stress, ↑leptin, ↓adiponectin. Liraglutide (5 weeks): reversed structural damage, ↓oxidative stress, normalized adipokines. C57BL/6 mice.","whyItMatters":"High salt intake is extremely common and damages fat tissue independently of blood pressure. Finding that GLP-1 drugs can reverse this damage provides a new rationale for their use in salt-sensitive metabolic dysfunction.","specificNumbers":"","methodology":"Male C57BL/6 mice: control vs 8% NaCl (HSD) for 15 weeks, then ± liraglutide for 5 weeks. VAT: histology, collagen, vascularization, mitochondrial dynamics, oxidative stress, adipokines.","limitations":"Mouse model. 8% NaCl is very high. 5-week treatment period. Male mice only. Mechanism of GLP-1 fat tissue repair not fully elucidated."},{"rthcId":"RPEP-13829","title":"Refractory Dysmenorrhea Managed With a Glucagon-Like Peptide-1 Agonist: A Case Report.","authors":"Tran, Mary; Swartz, Nicholas; Elisèe, Sabine D","year":2025,"journal":"Cureus, 17(1), e77387","doi":"10.7759/cureus.77387","pmid":"39944451","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Severe refractory dysmenorrhea → resolved with semaglutide. No weight change. Transient appetite loss only. No new medications added. No lifestyle changes. Proposed mechanisms: anti-estrogenic + anti-inflammatory. First case report.","whyItMatters":"Dysmenorrhea affects millions of women with limited options when NSAIDs and hormones fail. A GLP-1 drug providing relief through non-weight-dependent mechanisms could expand treatment options for refractory menstrual pain.","specificNumbers":"","methodology":"Single case report.","limitations":"Single case. Cannot prove causation. Placebo effect possible. Mechanism hypothesized not proven."},{"rthcId":"RPEP-13830","title":"The Potential Effect of Endogenous Antimicrobial Peptides in Cancer Immunotherapy and Prevention.","authors":"Tran, Tuan Hiep; Le, Thanh Huong; Tran, Thi Thu Phuong","year":2025,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 31(2), e3664","doi":"10.1002/psc.3664","pmid":"39716371","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"AMPs with anticancer activity: LL-37, HNP, lactoferrin. Mechanisms: apoptosis induction, wound healing, immune modulation. Advantages: abundance, bioavailability, safety, immune compatibility. Applications: standalone or with immunotherapy.","whyItMatters":"Cancer immunotherapy often lacks selectivity between normal and cancer cells. AMPs' natural selectivity and immune-enhancing properties could improve immunotherapy precision and effectiveness.","specificNumbers":"","methodology":"Narrative review of endogenous AMP anticancer properties and immunotherapy potential.","limitations":"Review format. Most anticancer data preclinical. AMP stability and delivery challenges. Not all AMPs are equally selective for cancer vs normal cells."},{"rthcId":"RPEP-13831","title":"Brain-Derived GLP-1-Understanding the Physiological Function and Anti-obesity Potential of Preproglucagon Neurons.","authors":"Trapp, Stefan; Skoug, Cecilia","year":2025,"journal":"Endocrinology, 166(12)","doi":"10.1210/endocr/bqaf169","pmid":"41222078","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Brain-derived GLP-1 (from PPG neurons) is the physiological brain GLP-1R agonist. PPG neurons: brainstem location, multiple populations. Dual function: eating suppression + stress association. Drug target: promising but stress effects need consideration. Different PPG populations may serve different functions.","whyItMatters":"Understanding that brain GLP-1—not gut GLP-1—drives appetite suppression fundamentally reframes how we think about GLP-1 drug mechanisms. The stress connection raises important safety and efficacy questions.","specificNumbers":"","methodology":"Critical narrative review of PPG neuron biology, GLP-1 production, brain GLP-1R pharmacology, and translational implications.","limitations":"Review format. PPG neuron stress association complicates therapeutic development. Species differences in PPG neuron populations. Human PPG neuron data limited."},{"rthcId":"RPEP-13832","title":"Efficacy and safety of once-daily oral semaglutide in patients with heart failure with preserved ejection fraction, type 2 diabetes and obesity: a real-world study.","authors":"Trenas, Alicia; Pérez-Velasco, Miguel A; Bernal-López, Maria-Rosa; López-Carmona, María-Dolores; Gómez-Doblas, Juan J; Martínez-Esteban, María-Dolores; Bouarich, Oumayma; García-Casares, Natalia; Fernández-García, Diego; de Lucas, María-Dolores García; Gómez-Huelgas, Ricardo; Pérez-Belmonte, Luis M","year":2025,"journal":"European journal of internal medicine, 139, 106378","doi":"10.1016/j.ejim.2025.06.007","pmid":"40518344","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Oral semaglutide in HFpEF + T2DM + obesity: improved health status (symptoms, function). Significant weight loss. First real-world oral semaglutide HFpEF data. Triple-pathology population.","whyItMatters":"Oral semaglutide offering HFpEF benefit eliminates the injection barrier for heart failure patients, potentially improving access and adherence for this common condition.","specificNumbers":"","methodology":"Prospective real-world study of oral semaglutide in HFpEF patients with T2DM and obesity.","limitations":"Real-world observational. No control group. Small sample likely. Short follow-up. Oral semaglutide doses are lower than injectable."},{"rthcId":"RPEP-13833","title":"GLP-1RA-Associated Diabetic Lumbosacral Radiculoplexus and Common Fibular Neuropathies: A Case-Control Evaluation.","authors":"Triplett, James D; Pinto, Marcus V; Young, Nathan P; Staff, Nathan P; Chinmay, Marathe S; Horowitz, Michael; Aragon Pinto, Catarina; Laughlin, Ruple S; Shouman, Kamal; Berini, Sarah E; Mauermann, Michelle L; Dubey, Divyanshu; Mandrekar, Jay; Dyck, P James B; Klein, Christopher J","year":2025,"journal":"Neurology, 105(3), e213916","doi":"10.1212/WNL.0000000000213916","pmid":"40694751","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"First case-control evaluation of GLP-1RA-associated DLRPN and CFN. Semaglutide already linked to NAION. Both neuropathies associated with weight loss. Possible mechanism: rapid weight loss → nerve ischemia/compression. Expands GLP-1 neurological safety profile.","whyItMatters":"As millions lose weight rapidly on GLP-1 drugs, peripheral nerve injuries from weight-related mechanisms may increase. Recognizing this association enables early diagnosis and management.","specificNumbers":"","methodology":"Case-control study evaluating GLP-1RA exposure in patients with DLRPN or CFN vs controls.","limitations":"Case-control design—cannot prove causation. Weight loss itself causes these neuropathies. Difficult to separate drug from weight loss effect. Specific results not detailed in abstract preview."},{"rthcId":"RPEP-13834","title":"Changes in β-Cell Function and Insulin Sensitivity During Treatment With Dapagliflozin Alone or in Combination With Exenatide in Type 2 Diabetes.","authors":"Triplitt, Curtis; Cersosimo, Eugenio; Alatrach, Mariam; Adams, John; Hansis-Diarte, Andrea; Baskoy, Gozde; Gastaldelli, Amalia; Chavez-Velazquez, Alberto; DeFronzo, Ralph A","year":2025,"journal":"Diabetes care, 48(9), 1545-1552","doi":"10.2337/dc25-0490","pmid":"40627548","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Dapagliflozin + exenatide: superior β-cell function improvement vs monotherapy. 90-minute OGTT assessment. 90 T2DM patients. Hypothesis confirmed: combination > individual agents for BCF. Insulin sensitivity also improved.","whyItMatters":"Understanding that combination therapy improves the actual function of insulin-producing cells—not just their surroundings—provides a mechanistic rationale for dual prescribing.","specificNumbers":"","methodology":"RCT. 90 T2DM patients. 3 arms: dapagliflozin, exenatide, combination. 180-min OGTT. Beta-cell function and insulin sensitivity assessment.","limitations":"Specific BCF metrics and effect sizes not in abstract preview. Relatively small (90 patients). OGTT is a research tool, not routine clinical practice."},{"rthcId":"RPEP-13835","title":"GLP-1 receptor agonists in Parkinson's disease progression: a meta-analysis with trial sequential analysis of randomized controlled trials.","authors":"Tsai, Wen-Wen; Lu, Kuan-Hsien; Wu, Jheng-Yan; Chuang, Min-Hsiang; Chen, Jui-Yi; Lai, Chih-Cheng; Hung, Kuo Chuan; Hsieh, Meng-Tsang","year":2025,"journal":"Therapeutic advances in neurological disorders, 18, 17562864251372747","doi":"10.1177/17562864251372747","pmid":"40951542","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Updated meta-analysis + TSA of GLP-1RA RCTs in PD. Motor and non-motor outcomes assessed. Safety profile evaluated. Mild-to-moderate PD patients. TSA determines evidence sufficiency.","whyItMatters":"PD has no disease-modifying treatment. This TSA-enriched analysis determines whether existing RCT evidence is sufficient to conclude GLP-1 drugs slow PD—or whether more trials are needed.","specificNumbers":"","methodology":"Systematic review, meta-analysis, and trial sequential analysis of RCTs. GLP-1RAs in mild-to-moderate PD. Motor (MDS-UPDRS) and non-motor outcomes.","limitations":"Meta-analysis depends on available RCTs. PD trials are small. Different GLP-1 drugs used. Short trial durations."},{"rthcId":"RPEP-13836","title":"The concentration-dependent protective effects by new generation hypoglycemic agents on delirium, depression, dementia and coma: evidence from a network meta-analysis.","authors":"Tseng, Ping-Tao; Zeng, Bing-Yan; Hsu, Chih-Wei; Suen, Mein-Woei; Hung, Chao-Ming; Carvalho, Andre F; Stubbs, Brendon; Chen, Yen-Wen; Chen, Tien-Yu; Lei, Wei-Te; Lin, Pao-Yen; Chen, Jiann-Jy; Su, Kuan-Pin; Wang, Hung-Yu; Zeng, Bing-Syuan; Shiue, Yow-Ling; Liang, Chih-Sung","year":2025,"journal":"Journal of the Royal Society of Medicine, 1410768251395877","doi":"10.1177/01410768251395877","pmid":"41359407","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Differential neuroprotective effects between individual GLP-1RAs and SGLT2i agents. Concentration-dependent responses identified. Four neurological outcomes: delirium, depression, dementia, coma. Agent-specific effects suggest personalized selection possible.","whyItMatters":"Not all GLP-1 drugs are equal for brain protection. Identifying which specific agents best protect against which neurological conditions enables precision prescribing for both metabolic and neurological benefit.","specificNumbers":"","methodology":"Network meta-analysis comparing individual GLP-1RA and SGLT2i agents for neurological outcomes (delirium, depression, dementia, coma).","limitations":"NMA indirect comparisons. Neurological outcomes from diabetes trials (not primary endpoints). Concentration-dependency inferred from dose, not measured levels."},{"rthcId":"RPEP-13837","title":"The gynecologic tumor risk related to GLP-1 receptor agonists and SGLT2 inhibitors use: a network meta-analysis of 91 randomized controlled trials.","authors":"Tseng, Ping-Tao; Zeng, Bing-Yan; Hsu, Chih-Wei; Sun, Cheuk-Kwan; Suen, Mein-Woei; Carvalho, Andre F; Stubbs, Brendon; Chen, Yen-Wen; Chen, Tien-Yu; Lei, Wei-Te; Chen, Po-Huang; Chen, Jiann-Jy; Shiue, Yow-Ling; Zeng, Bing-Syuan; Su, Kuan-Pin; Liang, Chih-Sung","year":2025,"journal":"Journal of hematology & oncology, 18(1), 109","doi":"10.1186/s13045-025-01750-x","pmid":"41310711","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"No overall increased gynecologic cancer risk with GLP-1RAs or SGLT2i. 91 RCTs included. NMA: regimen-specific comparisons. First comprehensive gynecologic cancer safety analysis for these drug classes. Addresses growing concern as prescribing increases in women.","whyItMatters":"With GLP-1 drugs increasingly prescribed to reproductive-age women (90% of new prescriptions non-diabetic in some countries), gynecologic cancer safety data is essential for informed prescribing.","specificNumbers":"","methodology":"Network meta-analysis of 91 RCTs comparing GLP-1RAs and SGLT2i. Gynecologic malignancy incidence as outcome.","limitations":"RCTs not designed for cancer endpoints. Cancer is rare—short trial durations may miss long-term risk. NMA indirect comparisons. Gynecologic cancer subtypes may have different risk profiles."},{"rthcId":"RPEP-13838","title":"Effectiveness of GLP-1 RAs and SGLT2 inhibitors in preventing T2DM in high-risk patients: an updated systematic review and meta-analysis.","authors":"Tsironikos, Georgios I; Tsolaki, Vasiliki; Zakynthinos, George E; Kyprianidou, Despoina; Rammou, Vasiliki; Antonogiannis, Thomas; Mprotsis, Theodoros; Zakynthinos, Epameinondas; Bargiota, Alexandra","year":2025,"journal":"Frontiers in clinical diabetes and healthcare, 6, 1694808","doi":"10.3389/fcdhc.2025.1694808","pmid":"41451292","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RAs + SGLT2i: both prevent T2DM in high-risk adults. Individual + combined effects assessed. Updated meta-analysis. Diabetes prevention paradigm.","whyItMatters":"Preventing diabetes is far more impactful than treating it. If GLP-1 drugs can keep high-risk individuals from developing T2DM, this could prevent millions of new diabetes cases worldwide.","specificNumbers":"","methodology":"Updated systematic review and meta-analysis of GLP-1RA and SGLT2i for T2DM prevention in high-risk populations.","limitations":"Meta-analysis. Prevention studies have various definitions of \"high-risk.\" Long-term prevention durability unknown after drug cessation."},{"rthcId":"RPEP-13839","title":"Liraglutide Attenuates FFA-Induced Retinal Pigment Epithelium Dysfunction via AMPK Activation and Lipid Homeostasis Regulation in ARPE-19 Cells.","authors":"Tsou, Sing-Hua; Luo, Kai-Shin; Huang, Chien-Ning; Kornelius, Edy; Cheng, I-Ting; Hung, Hui-Chih; Hung, Yu-Chien; Lin, Chih-Li; Hsu, Min-Yen","year":2025,"journal":"International journal of molecular sciences, 26(8)","doi":"10.3390/ijms26083704","pmid":"40332323","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Liraglutide: ↓FFA-induced RPE dysfunction. Mechanism: AMPK activation + lipid homeostasis regulation. Protected against: oxidative stress, lipid dysregulation, cellular dysfunction. AMD pathology-relevant model (ARPE-19 cells + FFA). Addresses drusen-related lipid accumulation.","whyItMatters":"AMD is the leading cause of irreversible blindness in the elderly with limited treatment for the dry (non-neovascular) form. Liraglutide addressing lipid-driven RPE damage could become the first treatment for dry AMD pathology.","specificNumbers":"","methodology":"In vitro ARPE-19 cells. FFA exposure model. Liraglutide treatment. AMPK pathway analysis. Lipid homeostasis markers. Oxidative stress assessment.","limitations":"In vitro single cell type. ARPE-19 is an immortalized cell line. FFA model is simplified vs in vivo AMD. Clinical doses may differ. AMD involves multiple cell types and pathways."},{"rthcId":"RPEP-13840","title":"Precision obesity medicine: A phenotype-guided framework for pharmacologic therapy across the lifespan.","authors":"Tuccinardi, Dario; Masi, Davide; Watanabe, Mikiko; Zanghi Buffi, Valeria; De Domenico, Francesco; Berti, Sabrina; Cipriani, Valentina; Manco, Melania; Manfrini, Silvia; Pagotto, Uberto","year":2025,"journal":"Journal of endocrinological investigation, 48(12), 2761-2798","doi":"10.1007/s40618-025-02700-7","pmid":"41212412","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Phenotype-guided framework: matches drug mechanism to patient profile. Drug options: GLP-1RA, GIP/GLP-1 (tirzepatide), triple agonists, combinations. Patient factors: metabolic, psychological, complications, age. Across lifespan: pediatric to elderly.","whyItMatters":"With 10+ obesity drugs available or emerging, clinicians need guidance on which drug to prescribe for which patient. This framework provides the first systematic approach to personalized obesity pharmacotherapy.","specificNumbers":"","methodology":"Narrative review proposing a precision medicine framework for obesity pharmacotherapy.","limitations":"Proposed framework—not validated in prospective studies. Evidence for some phenotype-drug matches is limited. Pediatric data sparse. Framework complexity may limit practical adoption."},{"rthcId":"RPEP-13841","title":"Impact of Glucagon-Like Peptide-1 Agonists on Hepatocellular Carcinoma Risk and Management in Type 2 Diabetes Mellitus: A Scoping Review.","authors":"Tungekar, Bassam; Echevarria Cruz, Evelyn C; Dodrill, Jason; Muneeb, Abdul; Sanderfoot, Rachel; Thaj, Omar; Vaishnav, Jeet; Vahidi, Arash; Hindi, Fadi; Khan, Rayyan; Nagy, Stephanie; Jacobs, Robin J","year":2025,"journal":"Cureus, 17(12), e100252","doi":"10.7759/cureus.100252","pmid":"41607999","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Preclinical: anti-tumor mechanisms (anti-inflammatory, anti-NAFLD, anti-proliferative). Some observational: protective signals. Large VA study: 31% HCC risk increase. Contradictory evidence. Need: longer-term studies. T2DM context.","whyItMatters":"With millions taking GLP-1 drugs, clarifying the HCC risk-benefit is critical. The contradictory evidence means clinicians must currently weigh potential liver protection against potential risk signals.","specificNumbers":"","methodology":"Scoping review of GLP-1RA effects on HCC risk and management in T2DM.","limitations":"Scoping review. Contradictory evidence not resolved. Preclinical ≠ clinical. Observational studies have confounding. No long-term dedicated HCC studies."},{"rthcId":"RPEP-13842","title":"The effects of liraglutide and metformin treatment on fracture healing in partially insulinopenic diabetic rats.","authors":"Turhan, Banu; Sağlam, Sönmez; Yücel, Mücahit Osman; Dalaslan, Raşit Emin; Sungur, Mehmet Ali; Demir, Fatih; Karaduman, Zekeriya Okan; Arıcan, Mehmet","year":2025,"journal":"Frontiers in endocrinology, 16, 1703958","doi":"10.3389/fendo.2025.1703958","pmid":"41195211","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Liraglutide + metformin: superior fracture healing vs monotherapy. Liraglutide: bone-protective effects. Metformin: metabolic benefits. Combination: complementary mechanisms. Partially insulinopenic diabetic rat model.","whyItMatters":"Diabetic patients have impaired fracture healing and increased fracture risk. Finding that liraglutide enhances healing—especially with metformin—supports using GLP-1 drugs in diabetic orthopedic patients.","specificNumbers":"","methodology":"Rat model of partially insulinopenic diabetes with induced fractures. Treatment groups: metformin, liraglutide, combination. Fracture healing assessment.","limitations":"Rat model. Partially insulinopenic (not typical T2DM). Specific healing metrics in full study. Translation to human fracture healing uncertain."},{"rthcId":"RPEP-13843","title":"Off-label GLP-1 weight-loss medicine use among online bodybuilders: Folk pharmacology, risk and harm reduction.","authors":"Turnock, Luke A; Hearne, Evelyn; Germain, Jennifer; Hirst, Mikey; Townshend, Honor D; Lazuras, Lambros","year":2025,"journal":"The International journal on drug policy, 142, 104854","doi":"10.1016/j.drugpo.2025.104854","pmid":"40418873","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Off-label GLP-1 use in bodybuilding: semaglutide, tirzepatide. Folk pharmacology: user-developed dosing/cycling protocols. Risk: unsupervised use, experimentation. Harm reduction: community-developed strategies. Online forums: primary information source.","whyItMatters":"A growing population is using GLP-1 drugs without medical supervision. Understanding their practices enables healthcare providers to engage these users with evidence-based guidance rather than driving them further from medical care.","specificNumbers":"","methodology":"Qualitative analysis of online bodybuilding forum discussions about GLP-1 drug use for physique enhancement.","limitations":"Qualitative study—cannot quantify prevalence. Online forums may not represent all users. Self-reported practices. No outcomes data."},{"rthcId":"RPEP-13844","title":"Semaglutide-Associated Gastric Pneumatosis.","authors":"Turunen, Andrew M; Coombs, Reilly A; Garg, Sushil Kumar","year":2025,"journal":"ACG case reports journal, 12(1), e01579","doi":"10.14309/crj.0000000000001579","pmid":"39734391","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"First case: gastric pneumatosis on semaglutide. Novel GI complication not previously described. GLP-1 drugs cause delayed gastric emptying (possible mechanism). Can be benign or indicate serious pathology.","whyItMatters":"With millions on semaglutide, even rare GI complications must be documented. Gastric pneumatosis can sometimes indicate life-threatening conditions, making recognition important.","specificNumbers":"","methodology":"Single case report.","limitations":"Single case. Cannot prove causation. Very rare. Gastric pneumatosis has multiple causes."},{"rthcId":"RPEP-13845","title":"Ghrelin-induced neuronal NPY promotes brain metastasis in lung cancer patients with low BMI.","authors":"Tyagi, Abhishek; Wu, Shih-Ying; Kim, Jee-Won; Deshpande, Ravindra Pramod; Wu, Kerui; Smith, Eleanor C; Banna, Giuseppe L; Watabe, Kounosuke","year":2025,"journal":"Nature communications, 16(1), 5608","doi":"10.1038/s41467-025-60730-4","pmid":"40595538","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Low BMI → ↑ghrelin → ↑neuronal NPY → NPY receptor activation on cancer cells → ↑brain metastasis. HFD (↓ghrelin) → ↓brain metastasis. NPY receptor blockade → ↓brain metastasis. Clinical: ↑ghrelin/NPY + ↑brain mets in low-BMI lung cancer. \"Obesity paradox\" explained.","whyItMatters":"Brain metastasis is often fatal. Understanding that lean patients' elevated ghrelin/NPY drives brain invasion provides a targetable mechanism—NPY receptor antagonists could prevent brain metastasis.","specificNumbers":"","methodology":"Clinical data: BMI, ghrelin, NPY, brain metastasis in lung cancer patients. Mouse models: HFD, NPY receptor blockade. In vitro: NPY effects on cancer cell invasion.","limitations":"Correlation between BMI and brain metastasis may have other explanations. Mouse HFD model is simplified. NPY receptor subtypes not differentiated. Clinical data observational."},{"rthcId":"RPEP-13846","title":"Metabolic rebound after GLP-1 receptor agonist discontinuation: a systematic review and meta-analysis.","authors":"Tzang, Chih-Chen; Wu, Pei-Hsun; Luo, Chiao-An; Chen, Zi-Ting; Lee, Yi-Ting; Huang, Ewen Shengyao; Kang, Yuan-Fu; Lin, Wei-Chen; Tzang, Bor-Show; Hsu, Tsai-Ching","year":2025,"journal":"EClinicalMedicine, 90, 103680","doi":"10.1016/j.eclinm.2025.103680","pmid":"41399474","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Weight regain: near-universal but variable rate. HbA1c: worsened. Cardiovascular parameters: deteriorated. Some residual benefit: may persist. Modifiers identified: treatment duration, lifestyle, individual factors. Comprehensive quantification of rebound.","whyItMatters":"Millions will eventually stop GLP-1 drugs (cost, shortage, personal choice). Quantifying what happens—and what modifies rebound—helps plan transitional care and manage expectations.","specificNumbers":"","methodology":"Systematic review and meta-analysis of GLP-1RA discontinuation studies in obesity, T2DM, and T1DM.","limitations":"Heterogeneous discontinuation studies. Variable follow-up durations. No standardized rebound definition. Some studies small."},{"rthcId":"RPEP-13847","title":"Highly Sensitive Assays for detection of headache inducing neuropeptides, Pituitary adenylate cyclase-activating polypeptide (PACAP) and Calcitonin gene-related peptide (CGRP).","authors":"Tzara, Ourania; Søderberg, Josefine Nielsen; Bahl, Justyna; Andersson, Emelie; Damlund, Dina Silke Malling; Vestergaard-Klewe, Ib; Harndahl, Mikkel Nors; Jensen, Allan; Asuni, Ayodeji A","year":2025,"journal":"medRxiv : the preprint server for health sciences","doi":"10.1101/2025.03.04.25323177","pmid":"40093232","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Highly sensitive PACAP + CGRP immunoassays developed. Clinical applications: migraine diagnosis, treatment monitoring, therapy selection. No current validated migraine biomarkers exist. Blood-based detection at clinically relevant levels.","whyItMatters":"Migraine diagnosis is entirely clinical (symptom-based) with no blood test. Having validated biomarkers could transform migraine from a subjective diagnosis to an objective, measurable condition.","specificNumbers":"","methodology":"Development and validation of highly sensitive immunoassays for PACAP and CGRP detection in blood samples.","limitations":"Assay development—clinical validation in large populations needed. Blood levels may not reflect brain levels. Multiple neuropeptides involved in migraine. Assay cutoffs not established."},{"rthcId":"RPEP-13848","title":"Semaglutide Improves Lipid Subfraction Profiles in Type 2 Diabetes: Insights from a One-Year Follow-Up Study.","authors":"Tóth, László Imre; Harsányi, Adrienn; Csiha, Sára; Molnár, Ágnes; Lőrincz, Hajnalka; Nagy, Attila Csaba; Paragh, György; Harangi, Mariann; Sztanek, Ferenc","year":2025,"journal":"International journal of molecular sciences, 26(13)","doi":"10.3390/ijms26135951","pmid":"40649729","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide vs sitagliptin (52 weeks): ↓BMI, WC, HbA1c, LDL-C, non-HDL-C. LDL subfractions: shifted to larger (less atherogenic). HDL subfractions: shifted to more protective. Multivariate: subfraction changes independent of BMI/HbA1c. Sitagliptin: modest HbA1c improvement only.","whyItMatters":"Lipoprotein subfraction profile is a better predictor of cardiovascular risk than total LDL. Semaglutide's ability to shift toward less atherogenic subfractions—independent of weight loss—reveals a direct anti-atherogenic mechanism.","specificNumbers":"","methodology":"52-week single-center RCT. 34 obese T2DM (18 semaglutide, 16 sitagliptin). 31 non-diabetic obese controls. Lipoprint gel electrophoresis for lipoprotein subfractions.","limitations":"Small RCT (34 patients). Single center. Lipoprint methodology limitations. Sitagliptin is a relatively weak comparator. Long-term cardiovascular endpoint correlation unknown."},{"rthcId":"RPEP-13849","title":"The effects of liraglutide on expressions of insulin secretion and beta cell survive associated GPCR genes in pancreatic beta cells.","authors":"Türkol, Melikenur; Bilgen, Türker","year":2025,"journal":"Turkish journal of medical sciences, 55(2), 525-530","doi":"10.55730/1300-0144.5997","pmid":"40342327","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Liraglutide modulates multiple GPCR genes in beta-cells. Affected pathways: insulin secretion + beta-cell survival. Systems-level reprogramming beyond GLP-1R alone. GPCRs: key drug targets in diabetes.","whyItMatters":"Understanding that liraglutide reprograms entire GPCR networks—not just activates one receptor—reveals why it has such broad metabolic effects and could guide design of improved GLP-1 drugs.","specificNumbers":"","methodology":"Beta-cell GPCR gene expression analysis after liraglutide treatment. Pathway analysis of insulin secretion and survival signaling.","limitations":"In vitro beta-cell study. Specific GPCR genes not detailed in abstract preview. Gene expression ≠ protein function. In vivo relevance needs confirmation."},{"rthcId":"RPEP-13850","title":"CGRP-related neuropeptide adrenomedullin 2 promotes tissue-protective ILC2 responses and limits intestinal inflammation.","authors":"Uddin, Jazib; Yano, Hiroshi; Parkhurst, Christopher N; Zhang, Wen; Ahmed, Anees; Ribeiro de Godoy, Victoria; Wei, Qianru; Panchakshari, Rohit; Henninot, Antoine; Dasgupta, Surya; Gaudino, Stephen; Emanuel, Elizabeth R; Zeng, Peng; Miranda, Isabella; Hu, Elin; Tsou, Amy M; Artis, David","year":2025,"journal":"Nature immunology, 26(9), 1516-1526","doi":"10.1038/s41590-025-02243-2","pmid":"40817416","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Enteric neurons produce ADM2 (CGRP-related peptide). ADM2 promotes tissue-protective ILC2 responses. ADM2 limits intestinal inflammation. New neuro-immune circuit identified. Differential: proinflammatory vs tissue-protective regulation.","whyItMatters":"Understanding how gut neurons promote healing (not just inflammation) through CGRP-related peptides could lead to new treatments for IBD and other intestinal inflammatory conditions.","specificNumbers":"","methodology":"Neuro-immune circuit analysis in gut. ADM2 production by enteric neurons. ILC2 response characterization. Intestinal inflammation models.","limitations":"Preclinical study. ILC2 biology is complex. Translation to human IBD needs validation. ADM2 receptor pharmacology not fully characterized."},{"rthcId":"RPEP-13851","title":"A brain-accessible peptide modulates stroke inflammatory response and neurotoxicity by targeting BDNF-receptor TrkB-T1 specific interactome.","authors":"Ugalde-Triviño, Lola; Tejeda, Gonzalo S; Esteban-Ortega, Gema M; Díaz-Guerra, Margarita","year":2025,"journal":"Theranostics, 15(10), 4654-4672","doi":"10.7150/thno.111272","pmid":"40225562","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Brain-accessible peptide targets TrkB-T1 (truncated BDNF receptor). Modulates: glia reactivity, neuroinflammation, excitotoxicity. TrkB-T1 interactome-specific targeting. Reduces stroke damage. Novel neuroprotective approach.","whyItMatters":"Stroke has limited treatment options beyond clot removal. A brain-accessible peptide that reduces inflammation and neurotoxicity through a novel target could provide neuroprotection during the critical post-stroke window.","specificNumbers":"","methodology":"Ischemic stroke models. Brain-accessible peptide design targeting TrkB-T1 interactome. Neuroinflammation and neurotoxicity assessment.","limitations":"Preclinical study. Brain accessibility of the peptide needs clinical confirmation. TrkB-T1 interactome complexity. Stroke models may not fully replicate human disease."},{"rthcId":"RPEP-13852","title":"Exenatide, a glucagon-like peptide-1 receptor agonist, may negatively impact bone healing in rats: histopathological, biochemical, and in silico findings.","authors":"Ugur, Fatih; Yilmaz, Ibrahim; Guner, Ersin; Albayrak, Mehmet; Taskin, Recep; Sarikas, Nurtac; Bildirici, Mehmet Akif; Dellalbasi, Ayse Basak; Ozcan, Candemir","year":2025,"journal":"Journal of orthopaedic surgery and research, 20(1), 883","doi":"10.1186/s13018-025-06300-2","pmid":"41063270","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Exenatide: impaired bone healing in rat cortical defect model. Evidence: histopathological (negative), biochemical (negative), in silico (negative). Contrast: liraglutide shows bone-protective effects. 42 male Sprague-Dawley rats.","whyItMatters":"With millions on GLP-1 drugs, understanding drug-specific bone effects is critical for fracture management. If exenatide impairs healing while liraglutide promotes it, drug selection matters for orthopedic patients.","specificNumbers":"","methodology":"42 male SD rats. Single radius cortical defect model. Exenatide treatment (excluding controls). Histopathological, biochemical, and in silico assessment.","limitations":"Rat model. Non-diabetic rats. Single GLP-1 drug tested. Doses may not reflect clinical use. Mechanism of impairment not fully explained."},{"rthcId":"RPEP-13853","title":"Trends in glucagon-like peptide 1 receptor agonist prescribing patterns.","authors":"Ukhanova, Maria; Wozny, Joseph S; Truong, Chau N; Ghosh, Lopita; Krause, Trudy M","year":2025,"journal":"The American journal of managed care, 31(8), e228-e234","doi":"10.37765/ajmc.2025.89778","pmid":"40829097","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 prescriptions surging. Barriers: insurance coverage gaps, high costs, premature non-specialist prescribing. Issues: suboptimal patient selection, inadequate monitoring. Need: improved coverage, cost solutions, specialist involvement.","whyItMatters":"The GLP-1 drug revolution benefits only those who can access and afford them. Understanding prescribing pattern problems enables targeted solutions for equitable, appropriate use.","specificNumbers":"","methodology":"Analysis of US GLP-1 prescribing patterns and trends.","limitations":"US-specific data. Rapidly evolving landscape. Cannot capture all prescribing nuances. Cost data varies by payer."},{"rthcId":"RPEP-13854","title":"GLP-1 receptor agonist increase retained gastric contents on EGD and same-day colonoscopy reduces this risk.","authors":"Ukwade, Dirin; Hernandez, Luis J; Modi, Zeel; Raza, Hasan S; Siegel, Michael; Nwachukwu, Dexter; Sarraf, Paya; Memon, Abdullah; Booth, Marya; Cooper, Karen; Boulay, Brian R; Mutlu, Ece A","year":2025,"journal":"Frontiers in medicine, 12, 1638981","doi":"10.3389/fmed.2025.1638981","pmid":"41001395","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 drug users: significantly ↑retained gastric contents on EGD. Same-day colonoscopy: ↓retained gastric content risk. Colonoscopy bowel prep: effectively empties stomach. Practical solution identified.","whyItMatters":"This provides a practical solution: when GLP-1 drug users need upper endoscopy, scheduling a same-day colonoscopy (with its bowel preparation) effectively prepares the stomach too.","specificNumbers":"","methodology":"Retrospective analysis of retained gastric contents during EGD in GLP-1RA users. Comparison: EGD alone vs same-day EGD + colonoscopy.","limitations":"Retrospective. Cannot determine optimal preparation protocol. Sample sizes in full study. Not all patients need colonoscopy."},{"rthcId":"RPEP-13855","title":"Effect of Anti-Diabetic Medication Use on Sepsis Risk in Type 2 Diabetes Mellitus: A Multivariate Analysis.","authors":"Ulambayar, Battamir; Ghanem, Amr Sayed; Nagy, Attila Csaba","year":2025,"journal":"Geriatrics (Basel, Switzerland), 10(4)","doi":"10.3390/geriatrics10040108","pmid":"40863575","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Multivariate analysis: different antidiabetic drugs have differential sepsis risk effects. GLP-1RAs + SGLT2i: potential sepsis risk reduction via anti-inflammatory/immune pathways. T2DM: increased sepsis risk from immune dysfunction/inflammation.","whyItMatters":"Sepsis kills millions of diabetics annually. Knowing which diabetes drugs reduce sepsis risk could guide drug selection for high-risk patients—adding infection prevention to metabolic management.","specificNumbers":"","methodology":"Multivariate analysis of antidiabetic medication use and sepsis risk in T2DM patients.","limitations":"Multivariate analysis from observational data. Confounding by indication likely. Cannot establish causation. Specific effect sizes not in preview."},{"rthcId":"RPEP-13856","title":"Immunomodulatory effects of anti-diabetic therapies: Cytokine and chemokine modulation by metformin, sodium-glucose cotransporter 2 inhibitors, and glucagon-like peptide-1 receptor agonists (2013-2025).","authors":"Ullah, Amin; Shen, Bairong","year":2025,"journal":"European journal of medicinal chemistry, 299, 118065","doi":"10.1016/j.ejmech.2025.118065","pmid":"40829258","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Three drug classes: distinct immunomodulatory profiles. Metformin: specific cytokine/chemokine modulation. SGLT2i: distinct immune effects. GLP-1RAs: specific immunomodulation. All: contribute to multi-organ protection beyond glucose. DM: metabolic + inflammatory disease.","whyItMatters":"Understanding each drug class's specific immune-modulating profile enables precision prescribing based on both metabolic and inflammatory needs—personalizing diabetes therapy.","specificNumbers":"","methodology":"Comprehensive review of cytokine and chemokine modulation by metformin, SGLT2i, and GLP-1RAs (2013-2025 literature).","limitations":"Review format. Cytokine effects may differ in vitro vs in vivo. Individual patient responses vary. Cannot determine which cytokine effects are most clinically important."},{"rthcId":"RPEP-13857","title":"Complete Heart Block: A Rare Initial Presentation of Epstein-Barr Virus-Induced Myocarditis.","authors":"Umar, Ridha; Moin, Kinza; Iqbal, Tarab; Sudha, Resshme K; Jaiganesh, Thiagarajan","year":2025,"journal":"Cureus, 17(1), e77884","doi":"10.7759/cureus.77884","pmid":"39991404","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13858","title":"Effect of Semaglutide Versus Placebo on Heart Failure With Preserved Ejection Fraction in Obese Patients: A Systematic Review.","authors":"Umaña Mejia, Carlos Alberto; Sañudo Soto, Claudia Victoria; Robalino, Juan; Hernández, Mayra; Santos Bretón, Myriam Bertha; Garcia-Vasquez, Edwin A; Rocha, Paola; Palacios Brambila, Luis Miguel; Morales, Sergio; Romo, Miguel; Castillo, Jaqueline L; Montelongo Quevedo, Mauricio; Flores Valdés, Jose R","year":2025,"journal":"Cureus, 17(6), e85250","doi":"10.7759/cureus.85250","pmid":"40605908","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide vs placebo in obese HFpEF: consistently improved symptoms, functional capacity, QoL, and weight. Insufficient evidence: mortality and HF hospitalization endpoints. Need: larger event-driven outcome trials.","whyItMatters":"While symptom improvement is meaningful for patients, regulatory approval and guideline inclusion for HFpEF require mortality/hospitalization data. This review precisely defines what we know and what gaps remain.","specificNumbers":"","methodology":"Systematic review of RCTs comparing semaglutide vs placebo in obese HFpEF.","limitations":"Systematic review of available trials. Hard endpoint data insufficient. Short trial durations for mortality outcomes. Specific effect sizes not in abstract preview."},{"rthcId":"RPEP-13859","title":"Prognostic impact of glucagon-like peptide-1 receptor (GLP1R) expression on cancer survival and its implications for GLP-1R agonist therapy: an integrative analysis across multiple tumor types.","authors":"Ungvari, Zoltan; Bartha, Áron; Ungvari, Anna; Fekete, Monika; Bianchini, Giampaolo; Győrffy, Balázs","year":2025,"journal":"GeroScience, 47(3), 4413-4427","doi":"10.1007/s11357-024-01494-5","pmid":"39777709","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13860","title":"Effect of acute treatment with the glucagon-like peptide-1 receptor agonist, liraglutide, and estrus phase on cue- and drug-induced fentanyl seeking in female rats.","authors":"Urbanik, Luke A; Booth, Jennifer L; Acharya, Nikhil K; Evans, Brianna B; Grigson, Patricia S","year":2025,"journal":"Behavioural pharmacology, 36(1), 16-29","doi":"10.1097/FBP.0000000000000805","pmid":"39718042","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Female rats readily self-administered fentanyl (1.85 μg/infusion IV) with marked individual differences in consumption patterns. Rats in estrus showed greater fentanyl intake, greater cue-induced fentanyl seeking, and greater drug-induced reinstatement of fentanyl seeking compared to those in non-estrus phases.\n\nAcute liraglutide treatment (0.3 mg/kg subcutaneous) produced two key effects: it reduced cue-induced fentanyl seeking, and it blocked drug-induced reinstatement of fentanyl seeking. These effects were particularly pronounced when rats were tested during estrus — the very phase associated with greatest vulnerability.\n\nThis extends previous findings in male rats to females, supporting the broad applicability of GLP-1 receptor agonists as potential non-opioid treatments for opioid use disorder across both sexes.","whyItMatters":"The opioid overdose crisis, now driven largely by fentanyl, kills over 100,000 Americans annually. Current medications for opioid use disorder (methadone, buprenorphine, naltrexone) are all opioid-based and have limitations. GLP-1 receptor agonists like liraglutide represent a completely different approach — targeting reward and motivation pathways through a non-opioid mechanism. The finding that liraglutide is most effective during the hormonal phase of greatest vulnerability is particularly significant for developing sex-specific treatment strategies.","specificNumbers":"","methodology":"Female Sprague-Dawley rats were trained to self-administer fentanyl intravenously (1.85 μg/infusion). Estrus cycle phase was tracked to assess hormonal influences on drug-taking behavior. After establishing self-administration, researchers tested cue-induced seeking (exposure to drug-associated cues without drug delivery) and drug-induced reinstatement (a prime dose of fentanyl triggering renewed seeking). Liraglutide (0.3 mg/kg) or vehicle was administered as a single subcutaneous injection before these tests. Individual differences in fentanyl intake patterns were also characterized.","limitations":"This is an animal study in rats, and addiction neurobiology differs between rodents and humans. The study used acute (single-dose) liraglutide, so chronic treatment effects are unknown. The fentanyl self-administration model, while well-established, cannot fully replicate the social, psychological, and environmental factors of human opioid use disorder. Sample sizes per group are not specified in the abstract. The 0.3 mg/kg dose in rats does not directly translate to human dosing. Only one GLP-1 agonist (liraglutide) was tested."},{"rthcId":"RPEP-13861","title":"Antidiabetic GLP-1 Receptor Agonists Have Neuroprotective Properties in Experimental Animal Models of Alzheimer's Disease.","authors":"Urkon, Melinda; Ferencz, Elek; Szász, József Attila; Szabo, Monica Iudita Maria; Orbán-Kis, Károly; Szatmári, Szabolcs; Nagy, Előd Ernő","year":2025,"journal":"Pharmaceuticals (Basel, Switzerland), 18(5)","doi":"10.3390/ph18050614","pmid":"40430434","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13862","title":"If the evidence is there, why are GLP-1 receptor agonists not on-label for hip and knee osteoarthritis in overweight patients?","authors":"Ursini, Francesco; Ciaffi, Jacopo; Caporali, Roberto","year":2025,"journal":"RMD open, 11(3)","doi":"10.1136/rmdopen-2025-006025","pmid":"40992788","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13863","title":"Safety and efficacy of glucagon-like peptide 1 receptor agonists in solid organ transplant recipients with diabetes mellitus: a systematic review and meta-analysis.","authors":"Usman, Muhammad; Yu, Hao; Chen, Xutao; Zhan, Yihua; Lai, Cong; Xu, Kewei","year":2025,"journal":"Kidney research and clinical practice, 44(6), 880-898","doi":"10.23876/j.krcp.24.271","pmid":"40905039","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13864","title":"Targeted Peptide Receptor Radionuclide Therapy With 177 Lu-DOTATATE Alters Joints Inflammation.","authors":"Usmani, Sharjeel; Rasheed, Rashid; Ahmed, Najeeb; Omar, Yehia; Numani, Shah P","year":2025,"journal":"Clinical nuclear medicine, 50(2), e102-e104","doi":"10.1097/RLU.0000000000005553","pmid":"39716406","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13865","title":"Impact of conservative versus conventional instrumentation on the release of inflammatory mediators and post-operative pain in mandibular molars with asymptomatic irreversible pulpitis: A randomized clinical trial.","authors":"Usta, Sıla Nur; Arias, Ana; Avcı, Emre; Silva, Emmanuel João Nogueira Leal","year":2025,"journal":"International endodontic journal, 58(6), 862-872","doi":"10.1111/iej.14224","pmid":"40085189","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13866","title":"Differential Treatment Effects on β-Cell Function Using Model-Based Parameters in Type 2 Diabetes: Results From the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE).","authors":"Utzschneider, Kristina M; Tripputi, Mark; Butera, Nicole M; Mari, Andrea; Rosin, Samuel P; Banerji, Mary Ann; Bergenstal, Richard M; Brown, Necole; Carlson, Anders L; DeFronzo, Ralph A; Gramzinski, Michaela R; Harindhanavudhi, Tasma; Kozedub, Alexandra; Sivitz, William I; Steffes, Michael W; Balasubramanyam, Ashok; Rasouli, Neda","year":2025,"journal":"Diabetes care, 48(4), 623-631","doi":"10.2337/dc24-2419","pmid":"39998948","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In the GRADE trial comparing four diabetes treatments added to metformin, liraglutide (the GLP-1 RA) produced the greatest improvements in beta-cell function. Liraglutide led to the largest increases in insulin secretion rate, glucose sensitivity, and potentiation, with values remaining above baseline even after 5 years. Sitagliptin improved glucose sensitivity with modest other effects. Glimepiride temporarily boosted insulin secretion but minimally affected glucose sensitivity. All treatments showed beta-cell function improvements at year 1 followed by progressive decline, and lower beta-cell function predicted earlier glycemic failure regardless of treatment.","whyItMatters":"Beta-cell decline is the core driver of type 2 diabetes progression. This analysis of the landmark GRADE trial reveals that liraglutide — a GLP-1 peptide drug — preserves beta-cell function better than three other major diabetes medications over 5 years. Despite this advantage, beta-cell function still declined with all treatments, highlighting that even the best available therapies cannot fully halt diabetes progression. Understanding how different drugs affect beta-cell physiology helps guide treatment selection.","specificNumbers":"n=4,712 · 4 treatment arms · 5-year follow-up · liraglutide had greatest ISR, glucose sensitivity, and potentiation increases · all treatments showed year 1 improvement then decline · glycemic failure defined as HbA1c >7.5%","methodology":"This analysis used data from the GRADE trial, a large comparative effectiveness study that randomized 4,712 adults with type 2 diabetes to insulin glargine, glimepiride, liraglutide, or sitagliptin added to metformin. Beta-cell function was assessed using mathematical modeling of oral glucose tolerance tests at baseline and years 1, 3, and 5. Linear mixed-effects models compared treatment effects, and Cox proportional hazards and CART analyses evaluated associations with glycemic failure.","limitations":"Beta-cell function was assessed via oral glucose tolerance test modeling rather than direct beta-cell measurements. The study cannot determine whether liraglutide's beta-cell benefits are direct effects on beta cells or secondary to improved metabolic conditions. The progressive decline in beta-cell function with all treatments suggests none fundamentally alters the disease trajectory."},{"rthcId":"RPEP-13867","title":"Liraglutide and empagliflozin alleviate diabetic cardiomyopathy by reducing oxidative stress and inflammation.","authors":"Uçar-Ekin, Cemre; Oflazoğllu-Diken, Huda; Baksi, Nazan; Aşir, Fırat; Şahika-Gökdemir, Gül","year":2025,"journal":"Gaceta medica de Mexico","doi":"10.24875/GMM.25000112","pmid":"41061250","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Liraglutide + empagliflozin: both ↓oxidative stress and ↓inflammation in DCM. Distinct but complementary mechanisms. Supports combination therapy rationale.","whyItMatters":"Understanding the complementary mechanisms of these two drug classes explains clinical trial findings and supports rational combination prescribing for diabetic heart protection.","specificNumbers":"","methodology":"Diabetic cardiomyopathy study; liraglutide vs empagliflozin vs combination; oxidative stress and inflammation markers.","limitations":"Preclinical study. Specific oxidative/inflammatory markers not detailed in abstract preview. Combination effects may differ in human hearts."},{"rthcId":"RPEP-13868","title":"Insights into the antifungal properties and modes of action of a recombinant hepcidin, rAd-Hep from the shrimp scad, Alepes djedaba (Forsskål, 1775).","authors":"V V, Anooja; S, Neelima; P P, Athira; M V, Anju; K, Archana; S Mohan, Anjali; M R, Revathy; Kesavan, Dhanya; Philip, Rosamma","year":2025,"journal":"Microbial pathogenesis, 203, 107518","doi":"10.1016/j.micpath.2025.107518","pmid":"40164398","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13869","title":"Real world effectiveness of anti-CGRP monoclonal antibodies over three consecutive one-year treatment cycles: An intention-to-treat analysis.","authors":"Vaghi, Gloria; Corrado, Michele; Pocora, Maria Magdalena; Bighiani, Federico; Cammarota, Francescantonio; Antoniazzi, Alessandro; Costantino, Luca; Martinelli, Daniele; Allena, Marta; Ghiotto, Natascia; Guaschino, Elena; Bottiroli, Sara; Iannone, Luigi Francesco; De Cesaris, Francesco; Montisano, Danilo Antonio; Grazzi, Licia; Sances, Grazia; Montomoli, Cristina; Tassorelli, Cristina; De Icco, Roberto","year":2025,"journal":"Cephalalgia : an international journal of headache, 45(8), 3331024251353421","doi":"10.1177/03331024251353421","pmid":"40770917","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Monthly migraine days were reduced consistently across three one-year treatment cycles: -12.7 days in year 1, -12.4 days in year 2, and -12.9 days in year 3. Baseline migraine days progressively decreased across cycles from 21.1 to 19.0 to 15.9, while residual migraine days decreased from 9.6 to 9.6 to 8.5.\n\nAt the end of year 3, the 50% response rate was 38.5% (69/179 patients) in this intention-to-treat analysis. The sustained reduction in monthly migraine days confirms long-term effectiveness, but the remaining high burden of disease in many patients underscores the need for additional treatment approaches and exploration of non-CGRP pathways.","whyItMatters":"Most anti-CGRP antibody clinical trials lasted only 3-6 months. This 3-year real-world study provides crucial long-term effectiveness data showing the drugs maintain their benefit without wearing off. The conservative intention-to-treat approach also gives a realistic picture of outcomes, including patients who discontinued — important for setting clinical expectations.","specificNumbers":"","methodology":"This was a prospective, real-world, intention-to-treat study enrolling 179 patients who started anti-CGRP monoclonal antibodies between 2018 and 2020. Clinical data were recorded using prospectively filled headache diaries across three consecutive one-year treatment cycles. Analysis used a multivariate linear mixed model including the entire enrolled population, regardless of whether they completed all cycles.","limitations":"This is an observational study without a control group, so natural fluctuations in migraine frequency cannot be fully accounted for. The 38.5% response rate at year 3 includes all enrolled patients (intention-to-treat), including those who discontinued, which is conservative but may underestimate effectiveness in patients who tolerate the treatment. Specific anti-CGRP antibodies used were not differentiated in the abstract. The cohort was primarily chronic migraine with medication overuse, limiting generalizability."},{"rthcId":"RPEP-13870","title":"Endobariatrics in the era of glucagon-like peptide-1 receptor agonists: evolving roles, evidence, and integration.","authors":"Vahedi, Farnoosh; Yalamanchi, Meghna; Issa, Danny","year":2025,"journal":"Current opinion in gastroenterology, 41(6), 380-388","doi":"10.1097/MOG.0000000000001134","pmid":"41025685","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13871","title":"GLP-1 Injectable Use Among Adults With Diagnosed Diabetes: United States, 2024.","authors":"Vahratian, Anjel; Warren, Antonia","year":2025,"journal":"NCHS data brief","doi":"10.15620/cdc/174616","pmid":"41022371","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13872","title":"Erythrina edulis (Pajuro): An Undervalued Alternative for the Generation of Bioactive Peptides with Nutraceutical Properties.","authors":"Valdez-Arana, Jenny-Del-Carmen; Espinoza-Villanueva, Lucia-Patricia; Cabrera-de-la-Cruz, Lady; Vidaurre-Ruiz, Julio","year":2025,"journal":"Plant foods for human nutrition (Dordrecht, Netherlands), 80(4), 176","doi":"10.1007/s11130-025-01420-w","pmid":"41116003","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13873","title":"Early combination therapy with SGLT2i and GLP-1 RA or dual GIP/GLP-1 RA in type 2 diabetes.","authors":"Vale, Catarina; Lourenço, Inês Mariana; Jordan, Gabriela; Golovaty, Ilya; Torres, Hugo; Moin, Tannaz; Buysschaert, Martin; Neves, João Sérgio; Bergman, Michael","year":2025,"journal":"Diabetes, obesity & metabolism, 27(2), 468-481","doi":"10.1111/dom.16077","pmid":"39604324","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13874","title":"The effect of glucagon-like Peptide-1 receptor agonists on measures of suicidality: A systematic review.","authors":"Valentino, Kyle; Teopiz, Kayla M; Cheung, William; Wong, Sabrina; Le, Gia Han; Rosenblat, Joshua D; Mansur, Rodrigo B; McIntyre, Roger S","year":2025,"journal":"Journal of psychiatric research, 183, 112-126","doi":"10.1016/j.jpsychires.2025.02.008","pmid":"39956093","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"This systematic review of 22 studies (10 pharmacovigilance, 12 cohort) found mixed results regarding GLP-1 receptor agonists and suicidality. Pharmacovigilance data showed disproportionate reporting of suicidal ideation for semaglutide and liraglutide specifically. However, cohort studies did not consistently show an increased risk of suicidality — and some GLP-1 RAs were actually associated with decreased suicidal ideation and suicide attempts. The authors concluded there is currently inadequate evidence to establish a causal link between GLP-1 RAs and suicidality.","whyItMatters":"With tens of millions of people now taking GLP-1 receptor agonists for diabetes and weight loss, understanding any potential psychiatric risks is critical. Reports to the FDA and EMA had raised alarm about possible links to suicidal thoughts, prompting this systematic review. The nuanced finding — that adverse event reports suggest a signal but real-world cohort data does not confirm it — helps clarify the actual risk landscape for prescribers and patients.","specificNumbers":"","methodology":"The researchers conducted a systematic review following PRISMA guidelines, searching seven databases (PubMed, Medline, Cochrane Library, PsychInfo, Embase, Scopus, and Web of Science) from inception through November 20, 2024, supplemented by manual Google Scholar searches. They included both pharmacovigilance studies (which analyze adverse event reports) and cohort studies (which follow patient populations over time). Cohort studies were assessed for quality using the Newcastle-Ottawa Scale. Suicidality was operationalized into three dimensions: suicidal ideation, suicide attempts, and suicide completion.","limitations":"Pharmacovigilance data relies on voluntary adverse event reporting, which is subject to reporting bias — increased media attention on GLP-1 drugs may inflate reporting rates. The review could not establish causality. Patients prescribed GLP-1 RAs for obesity and diabetes already have higher baseline rates of mental illness, making it difficult to separate drug effects from underlying risk. The heterogeneity of study designs limits direct comparison across the 22 included studies."},{"rthcId":"RPEP-13875","title":"FIB-4 predicts events in compensated advanced chronic liver disease and type 2 diabetes treated with GLP-1-receptor-agonists.","authors":"van Beurden, Wiebke; Mendoza, Yuly P; Lange, Naomi F; Bosch, Jaime; Berzigotti, Annalisa; Rodrigues, Susana G","year":2025,"journal":"Journal of diabetes and its complications, 39(3), 108978","doi":"10.1016/j.jdiacomp.2025.108978","pmid":"39999536","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13876","title":"Med14 phosphorylation shapes genomic response to GLP-1 Agonist.","authors":"Van de Velde, Sam; Yu, Jingting; Evensen, K Garrett; Pakhlevanyan, Edmund; Williams, April E; Shaw, Reuben J; Montminy, Marc","year":2025,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2025.06.17.660196","pmid":"40667025","tags":["glp-1","mechanism-of-action"],"studyType":"basic-research","evidenceStrength":"preliminary","keyFinding":"Researchers discovered that GLP-1 receptor agonists (specifically Exendin-4) work on pancreatic beta cells through a previously unknown mechanism involving a protein called Med14. When Exendin-4 activates the GLP-1 receptor, the signaling cascade triggers PKA to phosphorylate Med14 at a specific site (Ser983). This phosphorylation event is essential for turning on beta cell-specific genes linked to diabetes.\n\nCritically, this Med14 pathway explains why sustained GLP-1 agonist exposure produces different effects than brief exposure. Short-term signaling activates immediate response genes, but long-term exposure activates a broader set of beta cell-protective genes through this Med14 mechanism. When researchers mutated the Med14 phosphorylation site, beta cell numbers decreased and the drug's gene-activating effects were suppressed.","whyItMatters":"GLP-1 agonists like semaglutide and exenatide are among the most successful drugs in modern medicine, yet exactly how they protect and maintain beta cells at the molecular level has remained incompletely understood. This study identifies a key missing piece — a master transcriptional switch (Med14) that explains how these drugs trigger broad, beneficial changes in gene expression specific to beta cells. Understanding this mechanism could eventually help design better GLP-1-based therapies.","specificNumbers":"Phosphorylation site: Med14 Ser983 · PKA recognition motif: RRXS · Mutation to alanine decreased beta cell numbers · Primary mouse beta cells used","methodology":"The researchers used a proteomic screen to search for proteins that mediate the long-term transcriptional effects of GLP-1 analogs in beta cells. They identified Med14 and characterized its phosphorylation by PKA at Ser983 using biochemical assays. They tested the functional importance of this phosphorylation by creating a mutation (Ser983 to alanine) that blocks it, then measured the effects on gene expression and beta cell numbers in primary mouse beta cells treated with Exendin-4.","limitations":"This is a preprint (bioRxiv) that has not yet undergone peer review. The experiments were conducted in mouse beta cells, and the findings may not fully translate to human cells. The study focused on Exendin-4 rather than the clinically dominant GLP-1 agonists like semaglutide or liraglutide, though the mechanism is expected to be shared. No in vivo animal or human data were presented."},{"rthcId":"RPEP-13877","title":"Impact of CGRP monoclonal antibody treatment on blood pressure in patients with migraine: A systematic review and potential clinical implications.","authors":"van der Arend, Britt W H; van Welie, Floor C; Olsen, Michael H; Versijpt, Jan; Van Den Brink, Antoinette Maassen; Terwindt, Gisela M","year":2025,"journal":"Cephalalgia : an international journal of headache, 45(1), 3331024241297673","doi":"10.1177/03331024241297673","pmid":"39877974","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"From 693 articles screened, only four studies met inclusion criteria for evaluating blood pressure effects of anti-CGRP monoclonal antibodies in migraine patients. Among these, only one study had low risk of bias, and it reported elevated blood pressure following initiation of anti-CGRP(R)-mAb treatment. The extreme scarcity of quality evidence on this cardiovascular safety concern highlights a major gap in the literature despite widespread use of these drugs.","whyItMatters":"Anti-CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab, eptinezumab) are now prescribed to millions of migraine patients. CGRP is a peptide that dilates blood vessels, so blocking it could logically raise blood pressure. If confirmed, this cardiovascular risk would be especially important for migraine patients, who already have elevated cardiovascular risk compared to the general population.","specificNumbers":"","methodology":"Systematic review searching PubMed, Cochrane Database, Web of Science, MEDLINE, and EMBASE through May 1, 2024. Inclusion criteria focused on randomized controlled trials and observational cohort or case-control studies examining blood pressure effects of anti-CGRP(R)-mAbs versus controls in migraine patients. Two independent reviewers performed study selection, data extraction, and risk of bias assessment.","limitations":"Only four studies met inclusion criteria, severely limiting the strength of conclusions. Most anti-CGRP clinical trials did not specifically assess blood pressure as an endpoint. The review could not perform a meta-analysis due to heterogeneity and limited data. Long-term cardiovascular outcomes beyond blood pressure changes were not assessed. The authors note that the current evidence base is insufficient to draw definitive conclusions."},{"rthcId":"RPEP-13878","title":"Genetic variation in the glucagon-like peptide-1 receptor protein encoding region is associated with higher heart rate variability, but not with neurodegeneration of the brain, retina, and peripheral nerves: The Maastricht study.","authors":"van der Heide, Frank C T; Steens, Indra L M; Singh-Manoux, Archana; Sabia, Séverine; Zhou, Tan Lai; Köhler, Sebastian; Schram, Miranda T; van der Kallen, Carla J H; Berendschot, Tos T J M; Webers, Carroll A B; van Greevenbroek, Marleen M J; Wesselius, Anke; Arts, Ilja C W; Jansen, Jacobus F A; Backes, Walter H; van Sloten, Thomas T; Blokland, Gabriëlla A M; Stehouwer, Coen D A","year":2025,"journal":"Cardiovascular diabetology, 24(1), 397","doi":"10.1186/s12933-025-02888-1","pmid":"41088211","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13879","title":"Parabrachial calcitonin gene-related peptide neurons sex-specifically modulate behavior in anxiety assays during alcohol withdrawal.","authors":"Van Doorn, C E; Tyree, J B; Jaramillo, A A","year":2025,"journal":"Frontiers in pharmacology, 16, 1750956","doi":"10.3389/fphar.2025.1750956","pmid":"41767234","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13880","title":"Parabrachial Calcitonin Gene-Related Peptide Neurons Sex-Specifically Modulate Anxiety in Alcohol Withdrawal.","authors":"Van Doorn, C E; Tyree, J B; Jaramillo, A A","year":2025,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2025.11.24.690162","pmid":"41394560","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13881","title":"Peptide Hormones and Bile Acids Shaping Immune Tolerance of the Liver: Implications and Applications.","authors":"van Niekerk, Gustav; Kumpanenko, Yana; Degryse, Joran; Fevery, Johan; Dallmeier, Kai","year":2025,"journal":"Protein & cell","doi":"10.1093/procel/pwaf096","pmid":"41208029","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13882","title":"Switching from ligand to receptor anti-calcitonin gene-related peptide (CGRP) antibodies or vice versa in non-responders: A controlled cohort study.","authors":"van Veelen, Nancy; van der Arend, Britt W H; Hiele, E; van Zwet, E W; Terwindt, Gisela M","year":2025,"journal":"European journal of neurology, 32(1), e16542","doi":"10.1111/ene.16542","pmid":"39607215","tags":[],"studyType":"cohort study","evidenceStrength":"moderate","keyFinding":"Migraine patients who didn't respond to their first anti-CGRP monoclonal antibody (either erenumab or fremanezumab) benefited from switching to the other class — ligand-targeting to receptor-targeting or vice versa. The 31 patients who switched experienced a reduction of 3.9 monthly migraine days compared to 36 control patients who returned to standard care (95% CI: -6.4 to -1.3, p = 0.004). This demonstrates that failure on one anti-CGRP antibody class doesn't mean the entire CGRP-targeting approach should be abandoned.","whyItMatters":"When a migraine patient doesn't respond to an anti-CGRP antibody, clinicians face a difficult decision: try the same class of drug (just a different brand), switch to a different CGRP-targeting mechanism, or abandon CGRP therapy entirely. This study provides the first controlled evidence that switching between ligand-targeting antibodies (like fremanezumab, which binds CGRP itself) and receptor-targeting antibodies (like erenumab, which blocks the CGRP receptor) can rescue patients who failed their first treatment.","specificNumbers":"n=67 · Switchers: n=31 · Controls: n=36 · -3.9 monthly migraine days vs. control · 95% CI: -6.4 to -1.3 · p=0.004","methodology":"This controlled cohort study included 67 patients who discontinued their first anti-CGRP monoclonal antibody (erenumab or fremanezumab) primarily due to poor response. Thirty-one patients switched to the other antibody class within 3 months, while 36 received standard care (controls). Allocation was pseudo-random based on treatment availability. Changes in monthly migraine days were compared at 3 months using a multivariate regression model adjusting for confounders.","limitations":"This is a non-randomized cohort study with pseudo-random allocation based on drug availability, not true randomization. The sample size of 67 is modest. The 3-month follow-up is relatively short for assessing sustained migraine prevention. Only two anti-CGRP antibodies were studied (erenumab and fremanezumab), not galcanezumab or eptinezumab. The study cannot determine which direction of switching (ligand→receptor or receptor→ligand) is more effective."},{"rthcId":"RPEP-13883","title":"Preoperative liraglutide modulates control of fat and glucose metabolism during cardiopulmonary bypass surgery.","authors":"van Wilpe, Robert; Hulst, Abraham H; Thiessen, Steven E; DeVries, J Hans; Preckel, Benedikt; Hermanides, Jeroen","year":2025,"journal":"Endocrine connections, 14(4)","doi":"10.1530/EC-24-0427","pmid":"39927559","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13884","title":"Carboxy-Amidated AamAP1-Lys has Superior Conformational Flexibility and Accelerated Killing of Gram-Negative Bacteria.","authors":"Van Wyk, Rosalind J; Serem, June C; Oosthuizen, Carel B; Semenya, Dorothy; Serian, Miruna; Lorenz, Christian D; Mason, A James; Bester, Megan J; Gaspar, Anabella R M","year":2025,"journal":"Biochemistry, 64(4), 841-859","doi":"10.1021/acs.biochem.4c00580","pmid":"39873636","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13885","title":"Kynurenic Acid Analog Attenuates the Production of Tumor Necrosis Factor-α, Calgranulins (S100A 8/9 and S100A 12), and the Secretion of HNP1-3, and Stimulates the Production of Tumor Necrosis Factor-Stimulated Gene-6 (TSG-6) but Does Not Alter IL-17 Levels in Whole-Blood Cultures of Patients with Spondyloarthritis.","authors":"Varga, Borisz; Toldi, Gergely; Vécsei, László; Mándi, Yvette; Balog, Attila","year":2025,"journal":"International journal of molecular sciences, 26(24)","doi":"10.3390/ijms262411801","pmid":"41465233","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13886","title":"Acute Interstitial Nephritis Induced by Monoclonal Antibodies Targeting Calcitonin Gene-Related Peptide (CGRP)-Unveiling a New Association: A Case Report.","authors":"Vargas-Brochero, Maria J; Mekraksakit, Poemlarp; Garg, Arvind K; Fervenza, Fernando C; Zand, Ladan","year":2025,"journal":"Kidney medicine, 7(10), 101092","doi":"10.1016/j.xkme.2025.101092","pmid":"41050120","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13887","title":"Weight change from incretin-based weight loss medications across categories of second-generation antipsychotics.","authors":"Varghese, Jithin Sam; Goldsmith, David R; Cotes, Robert O; Ravikumar, Vishnu; Ali, Mohammed K; Pasquel, Francisco J","year":2025,"journal":"International journal of obesity (2005), 49(12), 2544-2548","doi":"10.1038/s41366-025-01885-4","pmid":"40817129","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13888","title":"D-enantiomeric antibiofilm peptides effective against anaerobic Cutibacterium acnes biofilm.","authors":"Varin-Simon, Jennifer; Haney, Evan F; Colin, Marius; Velard, Frédéric; Gangloff, Sophie C; Hancock, Robert E W; Reffuveille, Fany","year":2025,"journal":"Microbiology spectrum, 13(5), e0252324","doi":"10.1128/spectrum.02523-24","pmid":"40130849","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13889","title":"Health care resource utilization and direct costs incurred over 12 months by patients with migraine initiating self-injectable calcitonin gene-related peptide monoclonal antibodies: A US real-world study.","authors":"Varnado, Oralee J; Brady, Brenna; Zagar, Anthony; Robles, Yvonne; Ó Céilleachair, Alan; Hoyt, Margaret","year":2025,"journal":"Journal of managed care & specialty pharmacy, 31(4), 351-365","doi":"10.18553/jmcp.2025.31.4.351","pmid":"40152794","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13890","title":"GLP-1 receptor agonist therapy and pregnancy: Evolving and emerging evidence.","authors":"Varughese, Maria S; O'Mahony, Fidelma; Varadhan, Lakshminarayanan","year":2025,"journal":"Clinical medicine (London, England), 25(2), 100298","doi":"10.1016/j.clinme.2025.100298","pmid":"39993530","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13891","title":"Phenome-Wide Risk Evaluation of GLP-1 Receptor Agonist Use in Type 2 Diabetes with Real-World Data Across Multiple Healthcare Systems.","authors":"Vashisht, Rohit; Dhruva, Sanket S; Patel, Ayan; Dahm, Lisa; Morris, Pagan; Gonzalez, David; Follett, Rob; Sirota, Marina; Singh, Karandeep; Han, Cora; Koliwad, Suneil; Butte, Atul J","year":2025,"journal":"medRxiv : the preprint server for health sciences","doi":"10.1101/2025.08.13.25333579","pmid":"40832397","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13892","title":"Emerging Use of BPC-157 in Orthopaedic Sports Medicine: A Systematic Review.","authors":"Vasireddi, Nikhil; Hahamyan, Henrik; Salata, Michael J; Karns, Michael; Calcei, Jacob G; Voos, James E; Apostolakos, John M","year":2025,"journal":"HSS journal : the musculoskeletal journal of Hospital for Special Surgery, 15563316251355551","doi":"10.1177/15563316251355551","pmid":"40756949","tags":[],"studyType":"systematic-review","evidenceStrength":"low","keyFinding":"This systematic review of 36 studies (35 preclinical, 1 clinical) found that BPC-157 enhances growth hormone receptor expression and promotes angiogenesis while reducing inflammatory cytokines. In animal models, BPC-157 improved functional, structural, and biomechanical outcomes across muscle, tendon, ligament, and bone injuries.\n\nThe sole clinical study was a retrospective review of 12 patients with chronic knee pain who received intraarticular BPC-157 injections — 7 of 12 reported pain relief lasting more than 6 months. BPC-157 has a half-life under 30 minutes, is metabolized in the liver, and cleared by the kidneys. No adverse effects were found in preclinical safety studies, but no clinical safety data exist.","whyItMatters":"BPC-157 is already widely used by athletes and clinicians despite having no FDA approval and being banned in professional sports. This review is the first systematic synthesis of the orthopaedic sports medicine literature, highlighting both the promising preclinical results and the near-total absence of human evidence — a gap that matters enormously given how many people are already using it.","specificNumbers":"544 articles identified · 36 studies included · 35 preclinical, 1 clinical · 7/12 patients reported relief >6 months · half-life <30 minutes · studies spanning 1993–2024","methodology":"Systematic review of English-language literature from PubMed, Cochrane, and Embase databases, from inception through June 2024. Two independent reviewers screened 544 articles in three phases, with disagreements resolved by group consensus and a third reviewer. PROSPERO was checked for existing or unpublished reviews. Thirty-six studies met inclusion criteria.","limitations":"Nearly all included studies (35 of 36) were preclinical animal research. The single clinical study was a small retrospective review of just 12 patients. No randomized controlled trials in humans were found. The review is limited to level IV and V evidence, and no clinical safety data exist. Manufacturing is unregulated, introducing contamination risks."},{"rthcId":"RPEP-13893","title":"Improved ovarian adiponectin system expression in polycystic ovary syndrome treated with exenatide.","authors":"Vatankhah, Asma; Jamhiri, Mohabbat; Vatankhah, Sima; Lorian, Keivan; Rezvani, Mohammad Ebrahim; Izadi, Mahin","year":2025,"journal":"Clinical and experimental reproductive medicine, 52(1), 98-100","doi":"10.5653/cerm.2024.06912","pmid":"39084682","tags":[],"studyType":"animal","evidenceStrength":"low-moderate","keyFinding":"Exenatide, a GLP-1 receptor agonist peptide, improved adiponectin signaling in rats with polycystic ovary syndrome (PCOS). PCOS rats showed diminished adiponectin levels and elevated adiponectin receptor 1 (Adipo-R1) mRNA. Treatment with exenatide at both 50 mg/kg and 100 mg/kg doses restored adiponectin expression and normalized Adipo-R1 levels, suggesting the peptide may improve PCOS through molecular regulation of the adiponectin system.","whyItMatters":"PCOS affects millions of women worldwide and is a leading cause of infertility. Understanding how GLP-1 receptor agonists like exenatide interact with the adiponectin pathway could reveal new therapeutic approaches for managing PCOS beyond its established role in diabetes and weight management.","specificNumbers":"n=28 rats · 4 groups of 7 · 50 and 100 mg/kg exenatide doses · p<0.05 for Adipo-R1 differences","methodology":"Experimental animal study using 28 female Wistar rats divided into four groups: normal control, PCOS+vehicle, PCOS+exenatide 50 mg/kg, and PCOS+exenatide 100 mg/kg. PCOS was induced with estradiol valerate. Adiponectin and Adipo-R1 mRNA expression was measured using semi-quantitative real-time PCR.","limitations":"This is an animal study with a small sample size (7 rats per group), so results may not directly translate to humans. The study used only mRNA expression as a readout without measuring protein levels or functional outcomes like fertility restoration."},{"rthcId":"RPEP-13894","title":"Fusion Outcomes of GLP-1 Agonist Therapy in Multilevel Cervical Spinal Fusion: A Propensity-Matched Analysis.","authors":"Vatsia, Sohrab K; Levidy, Michael F; Rowe, Nicholas D; Meister, Andrew S; Bible, Jesse E","year":2025,"journal":"Clinical spine surgery, 38(4), 213-216","doi":"10.1097/BSD.0000000000001775","pmid":"40042198","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13895","title":"Branched tetrameric lactoferricin peptides modified with diaminopropionic acid exhibit potent antimicrobial and wound-healing activities.","authors":"Vavilthota, Nikitha; Babuççu, Gizem; Cordfunke, Robert A; de Boer, Leonie; Balraadjsing, Payal; Boekema, Bouke K H L; Drijfhout, Jan W; Riool, Martijn; Zaat, Sebastian A J","year":2025,"journal":"Frontiers in pharmacology, 16, 1719557","doi":"10.3389/fphar.2025.1719557","pmid":"41409598","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13896","title":"Investigation of serum biomarkers in rheumatoid and psoriatic arthritis patients for disease-specific signatures.","authors":"Veale, James D; Gorman, Áine; Veale, Douglas J; Fearon, Ursula; Orr, Carl; Marzaioli, Viviana","year":2025,"journal":"Arthritis research & therapy, 27(1), 147","doi":"10.1186/s13075-025-03608-6","pmid":"40640860","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13897","title":"Intracellular Transport of Monomeric Peptides, (Poly)Peptide-Based Coacervates and Fibrils: Mechanisms and Prospects for Drug Delivery.","authors":"Vedekhina, Tatiana; Pavlova, Iuliia; Svetlova, Julia; Khomyakova, Julia; Varizhuk, Anna","year":2025,"journal":"International journal of molecular sciences, 26(22)","doi":"10.3390/ijms262211015","pmid":"41303497","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13898","title":"Efficacy and Safety of Glucagon-Like Peptide-1 Receptor Agonists for Obesity Management in Adults With and Without Type 2 Diabetes: A Systematic Review.","authors":"Velji-Ibrahim, Jena; Radadiya, Dhruvil; Devani, Kalpit; Patel, Harsh; Nathani, Piyush; Hassan, Cesare; Pugliese, Nicola; Thompson, Christopher; Sharma, Prateek","year":2025,"journal":"Journal of obesity, 2025, 3897161","doi":"10.1155/jobe/3897161","pmid":"41211586","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13899","title":"Therapeutic Peptides Mitigates TLR4 Pathway Activation by Ang II in Renal and Vascular Smooth Muscle Cells.","authors":"Venkadakrishnan, Jegadheeswari; Vemana, Anusha; Ghatage, Trupti; Vesmaker, Kushal; Bhat, Audesh; Jadhav, Kirtikumar B; Dhar, Arti","year":2025,"journal":"Journal of biochemical and molecular toxicology, 39(11), e70579","doi":"10.1002/jbt.70579","pmid":"41186244","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The peptides Angiotensin 1-7 (Ang 1-7) and Brain Natriuretic Peptide (BNP) significantly reduced TLR4-mediated injury in renal and vascular smooth muscle cells stimulated by Angiotensin II. Specifically, these peptides reversed the upregulation of inflammation, fibrosis, and hypertrophy markers caused by Ang II, and prevented the harmful phenotypic switch in vascular smooth muscle cells.\n\nThe protective effects operated through inhibition of the TLR4 signaling pathway, a key driver of end-organ damage in hypertension.","whyItMatters":"Hypertension causes progressive damage to kidneys and blood vessels, partly through Angiotensin II activating inflammatory pathways. This study identifies two natural peptides — Ang 1-7 and BNP — that can block this damage at a key signaling checkpoint (TLR4). If these findings translate beyond cell studies, peptide-based therapies could offer a new approach to preventing the organ damage that makes hypertension so dangerous.","specificNumbers":"","methodology":"Researchers used three cell types — renal epithelial cells (RECs), renal fibroblasts (RFbs), and primary vascular smooth muscle cells (VSMCs) — to model organ damage caused by Angiotensin II. They measured gene expression of TLR4 and its downstream markers via qPCR, and assessed inflammatory, hypertrophic, and fibrotic markers using qPCR and immunocytochemistry, with and without Ang 1-7 and BNP treatment.","limitations":"This is an in vitro (cell culture) study only — no animal or human experiments were conducted. The protective effects observed in isolated cells may not directly translate to whole-organ or whole-body responses. Dosing, timing, and delivery challenges for clinical use are not addressed."},{"rthcId":"RPEP-13900","title":"Antimicrobial peptides from earthworms: Emerging candidates for novel therapeutic applications.","authors":"Venkatachalam, Saravanakumar; Selvan Christyraj, Johnson Retnaraj Samuel; Don Bosco, Reiya Bosco; Yesudhason, Beryl Vedha","year":2025,"journal":"Toxicon : official journal of the International Society on Toxinology, 264, 108458","doi":"10.1016/j.toxicon.2025.108458","pmid":"40499792","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13901","title":"Design, evaluation, and in vitro-in vivo correlation of self-nanoemulsifying drug delivery systems to improve the oral absorption of exenatide.","authors":"Venkatasubramanian, Ramakrishnan; Al-Maghrabi, Passant M; Alavi, Oscar; Lind, Tania; Sassene, Philip Jonas; Kirkensgaard, Jacob J K; Mota-Santiago, Pablo; Rades, Thomas; Müllertz, Anette","year":2025,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 379, 440-451","doi":"10.1016/j.jconrel.2025.01.013","pmid":"39805462","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13902","title":"Predictors of Placebo Response in the Study of Oxytocin in Autism to Improve Reciprocal Social Behaviors.","authors":"Verdes, Alyssa; Bhattachan, Suvekcha; Kolevzon, Alexander; King, Bryan H; McDougle, Christopher J; Sanders, Kevin B; Kim, Soo-Jeong; Spanos, Marina; Chandrasekhar, Tara; Rockhill, Carol; Palumbo, Michelle; Minjarez, Mendy; Nowinski, Lisa; Marler, Sarah; Siecinski, Stephen; Giamberardino, Stephanie; Gregory, Simon G; Veenstra-VanderWeele, Jeremy; Sikich, Linmarie; Jutla, Amandeep","year":2025,"journal":"Journal of child and adolescent psychopharmacology, 35(4), 202-210","doi":"10.1089/cap.2024.0131","pmid":"39970017","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13903","title":"Glucagon-like Peptide-1 Boosts Plumbagin's Neuroprotection Against Rotenone-Induced Motor Deficits.","authors":"Verma, Aanchal; Goyal, Ahsas","year":2025,"journal":"Current protein & peptide science","doi":"10.2174/0113892037402724251006011830","pmid":"41140083","tags":[],"studyType":"animal","evidenceStrength":"preliminary","keyFinding":"In a rotenone-induced rat model of Parkinson's disease, the plant compound plumbagin (20 mg/kg orally) improved motor deficits and increased both dopamine and GLP-1 peptide levels in the brain. Plumbagin also reduced RAGE (receptor for advanced glycation end products) levels, a marker of neuroinflammation.\n\nThe findings suggest that plumbagin's neuroprotective effects may be mediated through activation of the GLP-1 signaling pathway, which has independently been shown to have neuroprotective properties in Parkinson's disease models.","whyItMatters":"GLP-1 receptor agonists are being actively investigated for neuroprotection in Parkinson's disease (with clinical trials underway for exenatide and liraglutide). This study adds a new dimension by showing that a plant-derived compound can boost endogenous GLP-1 levels in the brain, potentially achieving similar neuroprotective benefits through a different mechanism than direct GLP-1 receptor agonist administration.","specificNumbers":"","methodology":"Male rats received rotenone (1.5 mg/kg subcutaneously) to induce Parkinson's-like motor deficits, then were treated with plumbagin (20 mg/kg orally). Motor function was assessed using multiple behavioral tests: actophotometer, beam walk, rotarod, gait analysis, open field, grip strength, and bar catalepsy. Brain levels of dopamine, GLP-1, and RAGE were measured.","limitations":"This is an animal study using a chemical model of Parkinson's disease (rotenone), which may not fully replicate human PD pathology. The study does not directly prove that GLP-1 pathway activation is the mechanism of plumbagin's effect — it only shows correlation between improved motor function and increased GLP-1 levels. Sample sizes and statistical details are not provided in the abstract."},{"rthcId":"RPEP-13904","title":"Therapeutic potential of small peptides in Alzheimer's disease: Advances in memory restoration and targeted delivery systems.","authors":"Verma, Poonam; Khatun, Rubina; Jew, Kiran Anjum; Prusty, Shakti Ketan; Knafo, Shira","year":2025,"journal":"Neuropeptides, 114, 102559","doi":"10.1016/j.npep.2025.102559","pmid":"40915260","tags":["neuroprotective-peptides"],"studyType":"narrative-review","evidenceStrength":"moderate","keyFinding":"Four small peptides show therapeutic potential for Alzheimer's disease by targeting amyloid toxicity, tau hyperphosphorylation, and synaptic degeneration at the molecular level. However, their clinical use is limited by poor bioavailability and rapid enzymatic breakdown.\n\nAdvanced delivery strategies — including intranasal administration, nanoparticle encapsulation, and chemical modifications — can overcome these barriers and significantly enhance the peptides' ability to reach brain targets and restore cognitive function.","whyItMatters":"Current Alzheimer's treatments mostly manage symptoms without addressing the underlying synaptic damage. Small peptides can interact with the specific molecular pathways driving the disease — amyloid buildup, tau tangles, and synapse loss. Combined with new delivery technologies, they represent a fundamentally different approach to slowing or potentially reversing cognitive decline in Alzheimer's patients.","specificNumbers":"4 small peptides reviewed · 3 delivery strategies assessed (intranasal, nanoparticle, chemical modification)","methodology":"Narrative review examining the mechanisms of action of four small peptides with demonstrated potential in alleviating Alzheimer's-related symptoms, along with evaluation of delivery systems that enhance their therapeutic efficacy, including intranasal routes, nanoparticle encapsulation, and chemical stabilization approaches.","limitations":"As a narrative review, this paper synthesizes existing preclinical and early-stage evidence rather than reporting new experimental data. Most of the peptide candidates discussed have not yet been tested in large human clinical trials. The review does not provide quantitative outcome data or statistical comparisons between delivery methods."},{"rthcId":"RPEP-13905","title":"Sex Differences in Effectiveness of Semaglutide in Patients With Peripheral Artery Disease: The STRIDE Trial.","authors":"Verma, Subodh; Catarig, Andrei-Mircea; Houlind, Kim; Ludvik, Bernhard; Nordanstig, Joakim; Rasouli, Neda; Sourij, Harald; Thomas, Sebastian; Nørgaard, Sidse K; Bonaca, Marc P","year":2025,"journal":"Journal of the American College of Cardiology, 86(20), 1843-1857","doi":"10.1016/j.jacc.2025.08.046","pmid":"40892617","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13906","title":"Action on elevated natriuretic peptide in primary care: a retrospective cohort study.","authors":"Vermeer, Cornelia Jc; Hollander, Monika; Stolk, Anne Jm; Groenewegen, Amy; Geersing, Geert-Jan; Rutten, Frans H; Hart, Huberta E","year":2025,"journal":"BJGP open, 9(1)","doi":"10.3399/BJGPO.2024.0017","pmid":"39231593","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13907","title":"Effectiveness and tolerability of atogepant in the prevention of migraine: A real life, prospective, multicentric study (the STAR study).","authors":"Vernieri, Fabrizio; Iannone, Luigi Francesco; Lo Castro, Flavia; Sebastianelli, Gabriele; De Santis, Federico; Corrado, Michele; Marcosano, Marilena; Ornello, Raffaele; Grazzi, Licia; Montisano, Danilo Antonio; De Cesaris, Francesco; Munafò, Antonio; Fofi, Luisa; Doretti, Alberto; Vaghi, Gloria; Pistoia, Francesca; Ferrandi, Delfina; Battistini, Stefania; Sacco, Simona; Guerzoni, Simona; Altamura, Claudia","year":2025,"journal":"Cephalalgia : an international journal of headache, 45(4), 3331024251335927","doi":"10.1177/03331024251335927","pmid":"40267275","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 106 patients (52.8% chronic migraine, 87.7% female, mean age 50.6):\n\n- Monthly migraine days decreased by 6.9 (SD 9.7, p<0.001) from baseline to 12 weeks\n- 50% response rate: 48.1% of patients achieved ≥50% reduction in migraine days\n- Significant reductions in acute medication use, disability scores (MIDAS), allodynia (ASC-12), and treatment optimization (mTOQ-6)\n- Quality of life improved (MSQ role-function restriction)\n- Only 6.6% dropout (4 for lack of efficacy, 3 for adverse events)\n- Prior failure on anti-CGRP monoclonal antibodies was NOT a negative prognostic factor in the regression analysis","whyItMatters":"Real-world data often differs from clinical trial results because real patients are more complex. This study confirms atogepant works well in everyday clinical practice, even in difficult-to-treat patients who have failed other CGRP-targeting therapies. This suggests the oral gepant works through a different enough mechanism to benefit patients who didn't respond to injectable antibodies.","specificNumbers":"","methodology":"Multicenter prospective observational cohort study (STAR study) across 10 Italian headache centers. 106 adult patients with clinical indication for atogepant 60 mg daily were assessed at baseline and 12 weeks using multiple validated migraine and disability questionnaires. Multiple regression analysis evaluated predictors of treatment response.","limitations":"Observational study without a placebo control group, so some improvement may reflect placebo effect or regression to the mean. Relatively small sample (106 patients) and short follow-up (12 weeks). Single-country (Italy) population may not generalize globally. The study was not blinded."},{"rthcId":"RPEP-13908","title":"Interventions for prediabetes: an umbrella review of systematic reviews and meta-analyses of randomized controlled trials.","authors":"Veronese, Nicola; Maggi, Stefania; Giussani, Cristina; Bianchini, Matteo; Alfadul, Hend; Sabico, Shaun; Al-Daghri, Nasser; Smith, Lee; Pizzol, Damiano; Limongi, Federica; Demurtas, Jacopo; Bartolini, Alessandra; Zanetti, Michela","year":2025,"journal":"Diabetes & metabolic syndrome, 19(9), 103303","doi":"10.1016/j.dsx.2025.103303","pmid":"41151201","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13909","title":"Calcitonin gene-related peptide-targeted therapy in migraine: current role and future perspectives.","authors":"Versijpt, Jan; Paemeleire, Koen; Reuter, Uwe; MaassenVanDenBrink, Antoinette","year":2025,"journal":"Lancet (London, England), 405(10483), 1014-1026","doi":"10.1016/S0140-6736(25)00109-6","pmid":"40121062","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13910","title":"Cardiovascular Therapeutics at the Crossroads: Pharmacological, Genetic, and Digital Frontiers.","authors":"Vetrano, Erica; Caturano, Alfredo; Nilo, Davide; Di Lorenzo, Giovanni; Tagliaferri, Giuseppina; Piacevole, Alessia; Donnarumma, Mariarosaria; Iadicicco, Ilaria; Picco, Sabrina; Moretto, Simona Maria; Rocco, Maria; Galiero, Raffaele; Russo, Vincenzo; Marfella, Raffaele; Rinaldi, Luca; Bonfrate, Leonilde; Sasso, Ferdinando Carlo","year":2025,"journal":"Pharmaceuticals (Basel, Switzerland), 18(11)","doi":"10.3390/ph18111703","pmid":"41304947","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13911","title":"A narrative review of glucagon-like peptide-1 receptor agonists prior to deep sedation or general anesthesia.","authors":"Vetrugno, Luigi; Deana, Cristian; Da Porto, Andrea; Boero, Enrico; Bellini, Valentina; Biasucci, Daniele Guerino; Bignami, Elena Giovanna","year":2025,"journal":"Journal of anesthesia, analgesia and critical care, 5(1), 16","doi":"10.1186/s44158-025-00237-y","pmid":"40156058","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13912","title":"Antimicrobial peptides derived from human ameloblastin targeting biofilms.","authors":"Vetyskova, Veronika; Kasparova, Petra; Bednarova, Lucie; Hajek, Miroslav; Luxa, Jan; Bautista, Alejandro Barrantes; Reseland, Jane Elin; Matatkova, Olga; Masak, Jan; Vondrasek, Jiri; Vydra Bousova, Kristyna","year":2025,"journal":"BMC oral health, 26(1), 24","doi":"10.1186/s12903-025-07433-w","pmid":"41331924","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13913","title":"Tirzepatide as a Potential Disease-Modifying Therapy in Lipedema: A Narrative Review on Bridging Metabolism, Inflammation, and Fibrosis.","authors":"Viana, Diogo Pinto da Costa; Invitti, Adriana Luckow; Schor, Eduardo","year":2025,"journal":"International journal of molecular sciences, 26(21)","doi":"10.3390/ijms262110741","pmid":"41226777","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13914","title":"The metabolic role of corticotropin-releasing hormone receptor 2 and its UCN peptides: emerging therapeutic potential.","authors":"Vidal, Pablo; Janzen, Natalie; Brozinick, Joseph T","year":2025,"journal":"Skeletal muscle, 16(1), 2","doi":"10.1186/s13395-025-00405-2","pmid":"41345730","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13915","title":"Improving sensitivity and drug tolerance of assays for neutralizing anti-drug antibodies to semaglutide and native GLP-1.","authors":"Videbæk, Nicoline; Jørgensen, Louise; de Lemos Rieper, Carina; Hummelshøj, Lone; Petersen, Steffan Svejgaard; Wøldike, Dorthe Bianca Corlin; Andresen, Lars Ole","year":2025,"journal":"Bioanalysis, 17(22), 1449-1460","doi":"10.1080/17576180.2025.2596576","pmid":"41334584","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13916","title":"Bariatric surgery and semaglutide in a youth with juvenile Huntington disease and severe obesity: a case report.","authors":"Vidmar, Alaina P; Martin, Matthew J; Abel, Stuart; Kim, Aimee G; Muñoz, Cynthia E; Weitzner, Madeleine; Derrington, Sabrina F; Samakar, Kamran","year":2025,"journal":"Journal of medical case reports, 19(1), 523","doi":"10.1186/s13256-025-05615-2","pmid":"41121434","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A 17-year-old male with juvenile Huntington disease and severe obesity (BMI 44 kg/m²) was treated with semaglutide starting at 0.25 mg weekly, titrated to 1 mg. After 3 months on semaglutide, his BMI decreased by 7% to 40 kg/m². He then underwent laparoscopic sleeve gastrectomy at age 18. Six months postoperatively, his BMI dropped to 33 kg/m², liver enzymes improved, obstructive sleep apnea resolved, and he reported improved physical activity and quality of life.","whyItMatters":"This case demonstrates that GLP-1 receptor agonists like semaglutide can be safely used as part of a multimodal obesity treatment approach even in patients with progressive neurodegenerative conditions. It raises important ethical questions about prioritizing quality of life in patients with limited life expectancy and shows that aggressive obesity management can yield meaningful benefits in complex pediatric cases.","specificNumbers":"n=1 · BMI 44 → 40 kg/m² (3 months semaglutide) · BMI 40 → 33 kg/m² (6 months post-surgery) · semaglutide 0.25–1 mg weekly · 7% BMI reduction on semaglutide alone","methodology":"This is a single case report describing the management of a 17-year-old male with juvenile Huntington disease and severe obesity. Treatment included semaglutide titrated from 0.25 mg to 1 mg weekly, followed by laparoscopic sleeve gastrectomy. Outcomes were tracked over 6 months postoperatively, measuring BMI, liver enzymes, sleep apnea status, and quality of life. Ethics consultation and shared decision-making with the family were integral to the treatment plan.","limitations":"As a single case report, these results cannot be generalized. The long-term outcomes of bariatric surgery and semaglutide in the context of progressive Huntington disease neurodegeneration are unknown. The follow-up period of 6 months post-surgery is relatively short. The relative contributions of semaglutide versus surgery to the overall outcome are difficult to separate."},{"rthcId":"RPEP-13917","title":"Semaglutide and laparoscopic sleeve gastrectomy in an adolescent with congenital adrenal hyperplasia due to 21-hydroxylase: a case report.","authors":"Vidmar, Alaina P; Kaiser, Linus; Martin, Matthew J; Abel, Stuart; Kim, Aimee G; Weitzner, Madeleine; Muñoz, Cynthia E; Fisher, Lynda K; Kim, Mimi S; Samakar, Kamran","year":2025,"journal":"Journal of medical case reports, 19(1), 37","doi":"10.1186/s13256-025-05047-y","pmid":"39863876","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13918","title":"The Right Approach: Power of Biomarkers in the Assessment and Management of Right Ventricular Dysfunction.","authors":"Viduljević, Mihajlo; Polovina, Marija; Geavlete, Oliviana; Adamo, Marianna; Hadžibegović, Adi; Ašanin, Milika; Stanković, Sanja; Ben Gal, Tuvia; Abdelwahab, Mohamed A; Abdelhamid, Magdy; Ambrosy, Andrew P; Chioncel, Ovidiu; Seferović, Petar M","year":2025,"journal":"International journal of molecular sciences, 26(18)","doi":"10.3390/ijms26189064","pmid":"41009628","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13919","title":"All-cause mortality and cardiovascular outcomes with glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes and heart failure with reduced ejection fraction.","authors":"Vignarajah, Aravinthan; Oro, Peter; El Dahdah, Joseph; Vigneswaramoorthy, Nishanthi; Vest, Amanda R; Shah, Gautam","year":2025,"journal":"American heart journal plus : cardiology research and practice, 60, 100676","doi":"10.1016/j.ahjo.2025.100676","pmid":"41323510","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13920","title":"Role of GLP-1 Receptor Agonists in Managing Cancer Therapy-Related Cardiac Dysfunction.","authors":"Vignarajah, Aravinthan; Kim, San; Albliwi, Moath; Ahn, Hyunjun Max; Izda, Aleksandar; Naffa, Faris; Vigneswaramoorthy, Nishanthi; Barot, Shimoli; Shah, Gautam","year":2025,"journal":"Journal of the American Heart Association, 14(22), e040919","doi":"10.1161/JAHA.125.040919","pmid":"41195790","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13921","title":"Exenatide once a week versus placebo as a potential disease-modifying treatment for people with Parkinson's disease in the UK: a phase 3, multicentre, double-blind, parallel-group, randomised, placebo-controlled trial.","authors":"Vijiaratnam, Nirosen; Girges, Christine; Auld, Grace; McComish, Rachel; King, Alexa; Skene, Simon S; Hibbert, Steve; Wong, Alan; Melander, Sabina; Gibson, Rachel; Matthews, Helen; Dickson, John; Carroll, Camille; Patrick, Abigail; Inches, Jemma; Silverdale, Monty; Blackledge, Bethan; Whiston, Jessica; Hu, Michele; Welch, Jessica; Duncan, Gordon; Power, Katie; Gallen, Sarah; Kerr, Jacqueline; Chaudhuri, K Ray; Batzu, Lucia; Rota, Silvia; Jabbari, Edwin; Morris, Huw; Limousin, Patricia; Greig, Nigel; Li, Yazhou; Libri, Vincenzo; Gandhi, Sonia; Athauda, Dilan; Chowdhury, Kashfia; Foltynie, Tom","year":2025,"journal":"Lancet (London, England), 405(10479), 627-636","doi":"10.1016/S0140-6736(24)02808-3","pmid":"39919773","tags":["glp-1-agonists","parkinsons-disease"],"studyType":"randomized-controlled-trial","evidenceStrength":"strong","keyFinding":"In this definitive phase 3 trial, the GLP-1 receptor agonist exenatide did NOT slow Parkinson's disease progression compared to placebo. After 96 weeks, Parkinson's motor symptoms worsened by 5.7 points in the exenatide group versus 4.5 points in the placebo group on the MDS-UPDRS III scale — no meaningful difference (p=0.47).\n\nThe drug was safe and well-tolerated, with serious adverse events actually slightly lower in the exenatide group (9% vs 11%). But the primary hypothesis — that exenatide could be a disease-modifying treatment for Parkinson's — was not supported by the data.","whyItMatters":"There had been enormous excitement about GLP-1 drugs potentially protecting the brain, fueled by lab studies showing neurotrophic properties and a smaller earlier trial suggesting benefits. This large, rigorous phase 3 trial is a reality check: exenatide does not appear to slow Parkinson's progression. It's an important negative result that redirects the field toward either different GLP-1 agents with better brain penetration or targeting specific patient subgroups who might still respond.","specificNumbers":"n=194 · 96 weeks · MDS-UPDRS III OFF worsening: +5.7 (exenatide) vs +4.5 (placebo) · p=0.47 · Serious adverse events: 9% vs 11% · Exenatide 2 mg/week subcutaneous","methodology":"Phase 3, multicentre, double-blind, parallel-group, randomised, placebo-controlled trial across 6 UK research hospitals. 194 participants with Parkinson's disease (Hoehn & Yahr stage ≤2.5, ages 25-80) were randomized 1:1 to exenatide 2 mg extended-release subcutaneous injection once weekly or placebo for 96 weeks. The primary outcome was change in MDS-UPDRS Part III motor score assessed while patients were off their dopaminergic medications, analyzed using intention-to-treat with linear mixed modeling.","limitations":"The trial used exenatide, an older GLP-1 agonist that may have limited brain penetration compared to newer agents like semaglutide. The sample size (194) may have been underpowered to detect subtle effects or benefits in subgroups. The study enrolled participants relatively early in their disease course (Hoehn & Yahr ≤2.5). COVID-19 pandemic overlap may have affected follow-up and participation."},{"rthcId":"RPEP-13922","title":"Exenatide Once Weekly in the Treatment of Patients with Multiple System Atrophy.","authors":"Vijiaratnam, Nirosen; Girges, Christine; Wiegand, Martin; Ismail, Claudia; Lameirinhas, Alexandra; Yarnall, Alison; Kirk, Cameron; Del-Din, Silvia; Rochester, Lynn; Kobylecki, Christopher; Ambler, Gareth; Skene, Simon; Houlden, Henry; Chelban, Viorica; Heslegrave, Amanda; Phillips, Wendy; Whone, Alan; Quinn, Niall; Lambert, Christian; Dore, Charlotte; Morris, Huw R; Horrocks, Mathew H; Lee, Ji Eun; O'Shaughnessy, Judi; Li, Yazhou; Greig, Nigel H; Gandhi, Sonia; Libri, Vincenzo; Athauda, Dilan; Foltynie, Tom","year":2025,"journal":"Annals of neurology, 98(5), 991-1003","doi":"10.1002/ana.70004","pmid":"40727970","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 50 MSA patients, exenatide-treated participants showed less worsening on the clinician/patient-rated UMSARS scale (6.1 vs 13.3 points at 48 weeks, adjusted difference -7.4 points, p=0.0003) — a seemingly impressive result. However, none of the objective secondary measures showed significant differences: ambulation loss, falls, speech, swallowing, timed walking, cognition, neurofilament light chain, CSF alpha-synuclein oligomers, gait sensors, or brain imaging were all similar between groups.\n\nThe authors candidly conclude that the discrepancy between the positive subjective primary outcome and the negative objective measures is likely due to placebo effects and observer bias inherent to the open-label design.","whyItMatters":"This is a cautionary tale for GLP-1 drug repurposing in neurodegenerative diseases. While exenatide showed neuroprotective effects in animal models of MSA, this human trial found that the apparent clinical benefit disappeared when measured objectively. The finding highlights the critical importance of double-blind trial design when testing peptide drugs for neurological conditions where placebo effects are strong. It also tempers enthusiasm about GLP-1 drugs as a treatment for neurodegenerative diseases beyond Parkinson's.","specificNumbers":"n=50 (25 per group) · 48-week treatment + 48-week washout · UMSARS difference -7.4 points (p=0.0003) · No significant objective differences · NfL, alpha-synuclein, gait, imaging all similar","methodology":"Single-center, randomized, open-label trial. 50 MSA patients randomized 1:1 to exenatide 2 mg subcutaneous weekly for 48 weeks or control, followed by 48-week washout. Primary outcome: UMSARS parts I+II combined score at 48 weeks. Secondary outcomes included objective measures of ambulation, falls, speech, swallowing, timed walking, quality of life, cognition, biomarkers (NfL, CSF alpha-synuclein oligomers), sensor-derived gait, and brain imaging.","limitations":"The open-label design is the critical limitation — patients and clinicians knew who received exenatide, allowing placebo effects and observer bias to inflate the subjective primary outcome. The lack of any objective measure improvement strongly suggests the primary outcome benefit was not a true drug effect. The sample size (n=50) limits power for secondary outcomes. MSA is a rapidly progressive disease, making it difficult to detect neuroprotective effects over 48 weeks."},{"rthcId":"RPEP-13923","title":"Comprehensive profiling of Apis cerana indica Fabricius crude venom: A dual approach using LCMS and GCMS.","authors":"Vikaash, Muthuraja; Kanagarajan, Rasappan; Manikandan, Eswaramoorthy; Dharani, Venkatraman","year":2025,"journal":"Toxicon : official journal of the International Society on Toxinology, 266, 108547","doi":"10.1016/j.toxicon.2025.108547","pmid":"40846141","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Using dual mass spectrometry approaches on electrically extracted Apis cerana indica venom:\n\n**High-molecular-weight compounds:**\n- 114 compounds identified across 69 protein families\n- Major Royal Jelly Proteins (MRJPs) were the most dominant family: MRJPs 1-7 all detected\n- MRJP 1 had the highest peptide match scores and spectrum matches among all venom proteins\n\n**Low-molecular-weight compounds:**\n- 159 total compounds detected\n- 136 metabolite compounds, dominated by fatty acid derivatives (42.05%)\n- 23 volatile compounds, dominated by alcohols (58.16%)\n\nThe study represents a substantial expansion of the known composition of A. cerana indica venom.","whyItMatters":"Honeybee venom has been used in traditional medicine for centuries and contains several compounds being investigated for modern therapeutics — including melittin (anti-cancer), apamin (neurological applications), and adolapin (anti-inflammatory). By comprehensively cataloging the composition of A. cerana indica venom, this study identifies the full repertoire of potentially bioactive compounds available for drug development. The unexpected dominance of Major Royal Jelly Proteins is particularly notable.","specificNumbers":"","methodology":"Venom was extracted from Apis cerana indica honeybees using electrical stimulation. Two untargeted mass spectrometry approaches were combined for maximum compound coverage: Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) for high-molecular-weight proteins and peptides, and Gas Chromatography-Tandem Mass Spectrometry (GC-MS/MS) for low-molecular-weight metabolites and volatile compounds.","limitations":"This is a descriptive proteomics study — no biological activities of the identified compounds were tested. The study used untargeted approaches, so quantification is relative rather than absolute. The unexpected dominance of MRJPs may reflect contamination from the bee's body during extraction. The venom was from a single collection, and composition may vary by season, diet, or colony. No comparison with A. mellifera venom was performed. Individual peptide sequences and their potential therapeutic activities were not characterized."},{"rthcId":"RPEP-13924","title":"Switching between anti-CGRP monoclonal antibodies in migraine prophylaxis.","authors":"Vikelis, Michail; Rikos, Dimitrios; Argyriou, Andreas A; Dermitzakis, Emmanouil V; Andreou, Anna P; Russo, Antonio","year":2025,"journal":"Expert review of neurotherapeutics, 1-16","doi":"10.1080/14737175.2025.2461766","pmid":"39884968","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13925","title":"Galcanezumab reduces trigeminal nociception and is effective in preclinical models of migraine and trigeminal autonomic cephalalgias.","authors":"Vila-Pueyo, Marta; Goadsby, Peter J; Johnson, Kirk W; Holland, Philip R","year":2025,"journal":"Headache, 65(10), 1693-1703","doi":"10.1111/head.15006","pmid":"40689463","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13926","title":"GLP-1-based therapies for obesity: Impact on comorbidities or obesity-related diseases.","authors":"Vilarrasa, Nuria; Pellitero, Silvia","year":2025,"journal":"Medicina clinica, 165(6), 107184","doi":"10.1016/j.medcli.2025.107184","pmid":"41016281","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13927","title":"Systematic review and meta-analysis of humoral immunity proteins and mortality in sepsis.","authors":"Villa, Antoine; Dewar, Fiona; Pisciotta, Walter; Rai, Ankit; Kerneis, Sven; Batum, Gül; McDonnell, Tom; Scully, Marie; McHugh, Timothy D; Hilpert, Kai; Gilroy, Derek; de Nooijer, Aline; Netea, Mihai G; Hedetoft, Morten; Bermejo-Martin, Jesús F; Akatsuka, Masayuki; Heinz, Corina C; Venet, Fabienne; Monneret, Guillaume; Meessen, Jennifer; Cheng, Tzu Hsuan; Zhang, Ming; Caironi, Pietro; Giamarellos-Bourboulis, Evangelos J; de la Torre Terrón, Mari C; Ebelt, Henning; Rademaker, Emma; Bodelsson, Mikael; Tverring, Jonas; Mi, Yuxin; Knight, Julian C; Lindsey, Merry L; Langley, Raymond J; Kingsmore, Stephen F; Brealey, Dave; Singer, Mervyn; Arulkumaran, Nishkantha","year":2025,"journal":"Critical care (London, England), 30(1), 41","doi":"10.1186/s13054-025-05758-0","pmid":"41430733","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13928","title":"Assessment of antigen immunogenicity formulated in minigenes transfected into antigen-presenting cells.","authors":"Villota-Alava, María A; Alfaro-Marenco, María A; Clavijo-Ramírez, Carlos A; Patarroyo, Manuel A; Parra-López, Carlos A","year":2025,"journal":"PloS one, 20(4), e0321392","doi":"10.1371/journal.pone.0321392","pmid":"40193826","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13929","title":"Efficacy and hypoglycaemia outcomes with once-weekly insulin icodec versus once-daily basal insulin in type 2 diabetes according to baseline glucagon-like peptide-1 receptor agonist and sodium-glucose co-transporter-2 inhibitor use: A post hoc analysis of ONWARDS 1-5.","authors":"Vilsbøll, Tina; Fu, Ariel; Kellerer, Monika; Kumar, Bharath; Søgaard, Stinne Byrholdt; Goldenberg, Ronald","year":2025,"journal":"Diabetes, obesity & metabolism, 27(6), 3165-3175","doi":"10.1111/dom.16328","pmid":"40098267","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across ONWARDS 1-5 (3,765 participants), 21.3% were using a GLP-1 RA and 36.9% were using an SGLT2i at baseline. There were no statistically significant treatment interactions by GLP-1 RA or SGLT2i subgroups for HbA1c change, body weight change (with one minor exception), weekly insulin dose, or achievement of HbA1c <7% without clinically significant hypoglycemia.\n\nRates of clinically significant or severe hypoglycemia were less than 1 episode per patient-year across all trials (except ONWARDS 4, a basal-bolus trial), regardless of GLP-1 RA/SGLT2i use. The efficacy and safety profile of icodec versus daily insulin was consistent across all subgroups.","whyItMatters":"Many diabetes patients today take GLP-1 drugs or SGLT2 inhibitors alongside insulin. Before prescribing a new once-weekly insulin, clinicians need to know it works well in combination with these background medications. This analysis provides the reassurance that switching to weekly icodec doesn't create unexpected interactions or reduce efficacy when patients are already on modern diabetes drug regimens.","specificNumbers":"","methodology":"Post hoc analysis of the randomized ONWARDS 1-5 trials. Participants with type 2 diabetes were analyzed by subgroups based on baseline GLP-1 RA and/or SGLT2i use. Treatment outcomes compared included HbA1c change, body weight change, weekly insulin dose, HbA1c target achievement, and hypoglycemia rates between icodec and daily basal insulin comparators.","limitations":"This is a post hoc analysis, not a prospectively designed subgroup study, so the comparisons were not powered for the specific subgroups analyzed. The GLP-1 RA and SGLT2i user subgroups were defined by baseline use but the specific drugs and doses varied. The exception in ONWARDS 5 for body weight by SGLT2i use suggests some potential interactions that need further investigation. As with all subgroup analyses, results should be interpreted with caution."},{"rthcId":"RPEP-13930","title":"HbA1c reduction with tirzepatide in people with type 2 diabetes: The contribution of weight loss assessed by a mediation analysis.","authors":"Vilsbøll, Tina; Malecki, Maciej T; Sharma, Palash; Thieu, Vivian T; Chivukula, Krishna Karthik; Kiljanski, Jacek","year":2025,"journal":"Diabetes, obesity & metabolism, 27(10), 5498-5505","doi":"10.1111/dom.16592","pmid":"40746012","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Mediation analysis across SURPASS-1, -2, and -5 trials (n=2,831) showed that tirzepatide's HbA1c reduction relative to placebo ranged from -14.6 to -20.0 mmol/mol, with weight loss mediating 12-27% of this effect in monotherapy and 25-45% with background insulin therapy. Relative to semaglutide 1 mg, the HbA1c difference ranged from -1.9 to -5.1 mmol/mol, with 54-71% mediated through weight loss. This demonstrates that tirzepatide's glycemic superiority involves substantial weight-loss-independent mechanisms, particularly when compared to placebo.","whyItMatters":"Understanding whether tirzepatide works primarily through weight loss or through direct metabolic effects is critical for clinical decision-making. If most of its benefit were from weight loss alone, patients who don't lose much weight might not see glycemic improvements. This analysis shows the opposite — tirzepatide has substantial direct effects on blood sugar control, meaning it can benefit patients regardless of how much weight they lose. It also helps explain why tirzepatide outperforms semaglutide despite both causing significant weight loss.","specificNumbers":"","methodology":"Post-hoc mediation analysis of three randomized, controlled, parallel, 4-arm Phase III SURPASS trials (SURPASS-1, -2, and -5) totaling 2,831 participants with type 2 diabetes. Weight-loss-dependent (WL-D) and weight-loss-independent (WL-IND) effects on comparator-adjusted HbA1c reduction at Week 40 were estimated, adjusting for baseline HbA1c and study-specific stratification factors.","limitations":"This is a post-hoc mediation analysis, not a pre-specified trial endpoint, which introduces analytical limitations. Mediation analysis assumes specific causal pathways that may not be fully validated. The comparison with semaglutide used only the 1 mg dose, not the higher 2 mg dose now commonly prescribed. The analysis cannot identify the specific weight-loss-independent mechanisms (e.g., direct insulin secretion effects, beta-cell function improvement, GIP receptor-specific effects)."},{"rthcId":"RPEP-13931","title":"Canadian Cardiovascular Society/Canadian Heart Failure Society 2025 Guideline Update for Pharmacologic Management of Heart Failure With Nonreduced Ejection Fraction (LVEF > 40%).","authors":"Virani, Sean; Zieroth, Shelley; Aleksova, Natasha; Anderson, Kim; Clarke, Brian; Ducharme, Anique; Ezekowitz, Justin A; Foroutan, Farid; Giannetti, Nadia; Jain, Rahul; Lee, Douglas; Lepage, Serge; Lyons, Kristin; McDonald, Michael; McGuinty, Caroline; Mielniczuk, Lisa; O'Meara, Eileen; Poon, Stephanie; Siatecki, Kyla; Swiggum, Elizabeth; Toma, Mustafa; Turgeon, Ricky D; Bains, Marc; Davis, Margot K; De, Sabe; Fine, Nowell; Heshka, Jodi; Keen, Sabina; King, Alexandra; Lavoie, Andrea; Mak, Susanna; McCleary, Lynn; Outbih, Oussama; Pike, Rodolfo; Sharma, Abhinav; Van Spall, Harriette G C; Yip, Amelia Ming Ching","year":2025,"journal":"The Canadian journal of cardiology, 41(10), 1857-1874","doi":"10.1016/j.cjca.2025.07.027","pmid":"41110921","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13932","title":"Unravelling the bioavailability of amino acids and bioactive peptides from collagen hydrolysate in coffee in healthy volunteers.","authors":"Virgilio, N; Schoen, C; van der Steen, B; Kleinnijenhuis, A J; van Holthoon, F L; Vleminckx, S; Silva, C I F; Prawitt, J","year":2025,"journal":"Food research international (Ottawa, Ont.), 211, 116478","doi":"10.1016/j.foodres.2025.116478","pmid":"40356137","tags":[],"studyType":"rct","evidenceStrength":"moderate","keyFinding":"Dissolving collagen hydrolysate in coffee altered the absorption of individual amino acids (hydroxyproline and proline showed significant variations) compared to dissolving it in water. However, the bioactive peptides themselves (Pro-Hyp, Hyp-Gly, Gly-Pro-Hyp) were absorbed similarly regardless of whether the collagen was mixed with water or coffee — the key pharmacokinetic measures (iAUC, peak concentration, time to peak) were equivalent.\n\nPeak concentrations of signature amino acids occurred between 60 and 120 minutes after intake. The polyphenols in coffee appear to affect free amino acid absorption but not the intact bioactive peptide fragments.","whyItMatters":"Millions of people add collagen powder to their morning coffee. Coffee is rich in polyphenols, which are known to bind to proline-rich proteins like collagen. This study answers a practical question many consumers have: does mixing collagen with coffee reduce its effectiveness? The reassuring finding is that the bioactive peptide fragments — the parts thought to deliver health benefits — are absorbed just as well from coffee as from water.","specificNumbers":"360-minute monitoring period · UPLC-MS/MS measurement · peak amino acid concentrations at 60–120 min · Hyp and Pro absorption significantly altered by coffee · Pro-Hyp, Hyp-Gly, Gly-Pro-Hyp absorption equivalent in water vs coffee","methodology":"Randomized, crossover clinical trial in healthy human volunteers. Participants received a single fasting dose of bovine collagen hydrolysate dissolved in either water or coffee. Blood samples were collected over 360 minutes and plasma concentrations of signature amino acids (hydroxyproline, glycine, proline) and bioactive peptides (Pro-Hyp, Hyp-Gly, Gly-Pro-Hyp) were measured using UPLC-MS/MS (ultra-performance liquid chromatography tandem mass spectrometry).","limitations":"The exact number of participants is not stated in the abstract. Single-dose fasting design doesn't capture how collagen performs with food or during repeated daily use. Only one coffee preparation was tested (variations in brew strength, temperature, and type could matter). Long-term health outcomes from collagen peptide absorption were not assessed."},{"rthcId":"RPEP-13933","title":"Therapeutic mRNAs for cancer immunotherapy: From structure to delivery.","authors":"Vishwakarma, Monika; Akram, Wasim; Haider, Tanweer","year":2025,"journal":"Advances in immunology, 165, 163-197","doi":"10.1016/bs.ai.2024.10.013","pmid":"40449973","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13934","title":"Gut Microbiome in Obesity: A Narrative Review of Mechanisms, Interventions, and Future Directions.","authors":"Vishwakarma, Ranjeet Kumar; Gautam, Priyanka; Sahu, Minakshi; Nath, Gopal; Yadav, Bhupendra Singh","year":2025,"journal":"Probiotics and antimicrobial proteins","doi":"10.1007/s12602-025-10855-1","pmid":"41313537","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13935","title":"Programmable short peptides for modulating stem cell fate in tissue engineering and regenerative medicine.","authors":"Vishwanath, Rohan; Biswas, Abhijit; Modi, Unnati; Gupta, Sharad; Bhatia, Dhiraj; Solanki, Raghu","year":2025,"journal":"Journal of materials chemistry. B, 13(8), 2573-2591","doi":"10.1039/d4tb02102a","pmid":"39871657","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13936","title":"Use of the BIOGROUP® French laboratories database to conduct CKD observational studies: a pilot EPI-CKD1 study.","authors":"Visseaux, Claire; Pénaranda, Guillaume; Conte, Cécile; Raguideau, Fanny; L'hirondel, Julien; Vignault, Claire; Zaoui, Philippe; Sebaoun-Rivière, Isabelle","year":2025,"journal":"Clinical chemistry and laboratory medicine, 63(8), 1610-1619","doi":"10.1515/cclm-2024-1399","pmid":"40101165","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13937","title":"Anorgasmia following initiation of GLP-1 agonist.","authors":"Visvabharathy, Vidya; MacPhedran, Sally; Shupp, Katie; King, Benjamin","year":2025,"journal":"Sexual medicine, 13(3), qfaf047","doi":"10.1093/sexmed/qfaf047","pmid":"40666108","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A female patient developed anorgasmia following initiation of a GLP-1 receptor agonist. The authors propose several mechanisms: the most likely being GLP-1 agonist-induced vasoconstriction of smooth muscle, which reduces oxygen delivery and blood flow to the genitals, hindering genital engorgement, arousal, and the smooth muscle contractions essential for orgasm.\n\nAdditional proposed mechanisms involve GLP-1 receptor modulation in the hypothalamus, which may decrease dopamine and norepinephrine signaling — neurotransmitters crucial for motivation, pleasure, and orgasm — and disrupt pathways involved in sexual desire and arousal.","whyItMatters":"Tens of millions of people worldwide are now taking GLP-1 receptor agonists for weight loss and diabetes. Sexual side effects are rarely discussed, rarely screened for, and may be significantly underreported due to patient embarrassment or lack of awareness. If GLP-1 agonists commonly impair sexual function, this would affect quality of life for a massive patient population and should factor into prescribing decisions and informed consent.","specificNumbers":"","methodology":"This is a clinical case report with chart review of a single patient who developed anorgasmia after starting a GLP-1 agonist. A Doctor of Pharmacy was consulted to explore possible pharmacological mechanisms by which GLP-1 agonists could affect sexual function.","limitations":"This is a single case report (n=1), the lowest level of clinical evidence. Causation cannot be established — the anorgasmia could be related to weight loss itself, psychological factors, hormonal changes, or other medications. The proposed mechanisms are theoretical and have not been experimentally validated. No specific GLP-1 agonist or dose is identified in the abstract. The prevalence of this side effect is entirely unknown."},{"rthcId":"RPEP-13938","title":"Influence of Hydrophobic Ion Pairing on Formulation Performance of Liraglutide in PLGA Microspheres.","authors":"Vitore, Jyotsna G; Yalamanda, Varla; Tomar, Devendra Singh; Rojekar, Satish; Rana, Dhwani; Benival, Derajram","year":2025,"journal":"AAPS PharmSciTech, 26(7), 199","doi":"10.1208/s12249-025-03195-4","pmid":"40730914","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13939","title":"Exploring omics signature in the cardiovascular response to semaglutide: Mechanistic insights and clinical implications.","authors":"Vitorino, Rui","year":2025,"journal":"European journal of clinical investigation, 55(2), e14334","doi":"10.1111/eci.14334","pmid":"39400314","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13940","title":"Synergistic Effect of Liraglutide and Strength-Endurance Exercise Training on Hepatic Oxidative Stress and Lipid Metabolism in Middle-Aged Male Rats.","authors":"Vlahović, Dragana; Trifunović, Svetlana; Borković-Mitić, Slavica; Pavlović, Slađan; Gizdović, Ivona; Lütjohann, Dieter; Filipović, Branko; Marina, Ljiljana; Šošić-Jurjević, Branka","year":2025,"journal":"Antioxidants (Basel, Switzerland), 14(12)","doi":"10.3390/antiox14121492","pmid":"41462691","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13941","title":"Artificial Intelligence and the Evolving Landscape of Immunopeptidomics.","authors":"Vo, Thanh Hoa; McNeela, Edel; O'Donovan, Orla; Rani, Sweta; Mehta, Jai Prakash","year":2025,"journal":"Proteomics. Clinical applications, 19(6), e70018","doi":"10.1002/prca.70018","pmid":"40741879","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13942","title":"Liraglutide upregulates the Cftr gene and regulates the mucus transcriptome profile in Brunner's glands in mice.","authors":"Voetmann, Louise Marie; Rolin, Bidda; Kirk, Rikke Kaae; Knudsen, Lotte Bjerre; Merkestein, Myrte; Ahnfelt-Rønne, Jonas; Kodal, Anne Louise; Jessen, Carsten; Ozen, Asli; Pyke, Charles; Hansen, Axel Kornerup","year":2025,"journal":"Clinical and translational medicine, 15(11), e70510","doi":"10.1002/ctm2.70510","pmid":"41146523","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13943","title":"Influence of triptans use on anti-CGRP mAbs response: a prospective, cohort study.","authors":"Vollono, Catello; Romozzi, Marina; Munafò, Antonio; Vigani, Giulia; De Cesaris, Francesco; Calabresi, Paolo; Iannone, Luigi Francesco","year":2025,"journal":"Journal of neurology, 272(7), 468","doi":"10.1007/s00415-025-13202-0","pmid":"40536712","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13944","title":"Amylin: From Mode of Action to Future Clinical Potential in Diabetes and Obesity.","authors":"Volčanšek, Špela; Koceva, Andrijana; Jensterle, Mojca; Janež, Andrej; Muzurović, Emir","year":2025,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 16(6), 1207-1227","doi":"10.1007/s13300-025-01733-8","pmid":"40332747","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13945","title":"Muscle Loss in Obesity Therapy as a Therapeutic Target: Trial Design and Endpoints for Regulatory Discussions.","authors":"von Haehling, Stephan; Sato, Ryosuke; Langer, Henning; Khan, Muhammad Shahzeb; Coats, Andrew J S; Evans, William; Heymsfield, Steven; Anker, Stefan D","year":2025,"journal":"Journal of cachexia, sarcopenia and muscle, 16(6), e70147","doi":"10.1002/jcsm.70147","pmid":"41362110","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13946","title":"Clinical characteristics and treatment patterns of patients with gastroenteropancreatic neuroendocrine neoplasia in Germany receiving peptide receptor radionuclide therapy: A real-world data registry-based study.","authors":"von Hessert-Vaudoncourt, Claus; Maasberg, Sebastian; Begum, Nehara; Rinke, Anja; Pöppel, Thorsten; Sipos, Bence; Grohe, Christian; Fottner, Christian; Stintzing, Sebastian; Grabowski, Patricia","year":2025,"journal":"Medicine, 104(11), e41853","doi":"10.1097/MD.0000000000041853","pmid":"40101049","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13947","title":"End-organ protective effect of serelaxin in patients hospitalized for heart failure: Results of the biomarker substudy of Relaxin in Acute Heart Failure-2 (RELAX-AHF-2).","authors":"Voors, Adriaan A; Metra, Marco; Postmus, Douwe; Greenberg, Barry H; Cotter, Gadi; Davison, Beth A; Beldhuis, Iris E; Felker, G Michael; Filippatos, Gerasimos; Pang, Peter S; Ponikowski, Piotr; Gimpelewicz, Claudio; Teerlink, John R","year":2025,"journal":"European journal of heart failure, 27(7), 1215-1223","doi":"10.1002/ejhf.3551","pmid":"39663924","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13948","title":"Antimicrobial Peptides of the Cathelicidin Family: Focus on LL-37 and Its Modifications.","authors":"Voronko, Olga Evgenevna; Khotina, Victoria Alexandrovna; Kashirskikh, Dmitry Alexandrovich; Lee, Arthur Anatolievich; Gasanov, Vagif Ali Oglu","year":2025,"journal":"International journal of molecular sciences, 26(16)","doi":"10.3390/ijms26168103","pmid":"40869425","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13949","title":"Glucagon-Like Peptide 1 Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors Improve Renal Resistive Index in Patients With Type 2 Diabetes: A 26-Week Prospective Observational Real-Life Study.","authors":"Vozza, Alfredo; Volpe, Sara; Custodero, Carlo; Colaianni, Valentina; Lavarra, Valentina; Triggiani, Domenico; Crudele, Lucilla; Bergamasco, Alessandro; Antonica, Gianfranco; Tortorella, Cosimo; Piazzolla, Giuseppina","year":2025,"journal":"Journal of diabetes research, 2025, 8182211","doi":"10.1155/jdr/8182211","pmid":"39963363","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13950","title":"Predictive factors of body weight loss in patients with type 2 diabetes treated with GLP-1 receptor agonists: a 52-week prospective real-life study.","authors":"Vozza, Alfredo; Triggiani, Domenico; Fanelli, Margherita; Lisco, Giuseppe; Coletto, Deborah; Custodero, Carlo; Volpe, Sara; Racaniello, Davide; Colaianni, Valentina; Lavarra, Valentina; Maggipinto, Rosselia; Portacci, Andrea; Tortorella, Cosimo; Moschetta, Antonio; Piazzolla, Giuseppina","year":2025,"journal":"Frontiers in endocrinology, 16, 1674308","doi":"10.3389/fendo.2025.1674308","pmid":"41079186","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13951","title":"Bioelectronic block of stellate ganglia mitigates pacing-induced heterogeneous release of catecholamine and neuropeptide Y in the infarcted pig heart.","authors":"Vrabec, Tina; Bender, Shane; Chan, Shyue-An; Cha, Steven; Haridas, Sahil; Hanna, Peter; Ajijola, Olujimi A; Shivkumar, Kalyanam; Smith, Corey; Ardell, Jeffrey L","year":2025,"journal":"The Journal of physiology, 603(7), 2071-2088","doi":"10.1113/JP286924","pmid":"39557601","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13952","title":"Semaglutide Plus Metformin Versus Metformin Alone For Antipsychotic-Induced Weight Gain In Patients With Type 2 Diabetes Mellitus.","authors":"Vu, Catherine; Thai, Raymond; Dike, Dozie; Sydner, Bria","year":2025,"journal":"The Psychiatric quarterly, 96(4), 819-827","doi":"10.1007/s11126-025-10137-7","pmid":"40227520","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13953","title":"New generation agents for glycemic control and diabetic retinopathy progression: what we need to know?","authors":"Vujosevic, Stela; Toma, Caterina; Ferrulli, Anna; De Cillà, Stefano; Nucci, Paolo; Luzi, Livio","year":2025,"journal":"Acta diabetologica, 62(10), 1573-1583","doi":"10.1007/s00592-025-02552-w","pmid":"40586870","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13954","title":"IL-33 as a Marker of Poor Early Response in Neuroendocrine Tumor Patients Undergoing Peptide Receptor Radionuclide Therapy.","authors":"Vuleta Nedic, Katarina; Gajovic, Nevena; Jovanovic, Ivan; Jurisevic, Milena; Jovanovic, Marina; Jakovljević, Slobodan; Popovic, Bojana; Djordjevic, Jelena; Ignjatovic, Vesna; Vukomanovic, Vladimir","year":2025,"journal":"International journal of molecular sciences, 26(17)","doi":"10.3390/ijms26178526","pmid":"40943444","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13955","title":"The potential role of GLP-1 receptor agonists in substance use disorders - a systematic review.","authors":"Völker, K M; Prechtl, B L H; Bormann, N L; Choi, D S","year":2025,"journal":"Frontiers in pharmacology, 16, 1702448","doi":"10.3389/fphar.2025.1702448","pmid":"41552827","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13956","title":"Bridging the Gap to Waitlist Activation: Semaglutide's Weight Loss Efficacy and Safety in Patients With Obesity on Dialysis Seeking Kidney Transplantation.","authors":"Wade, Francis G; Lentine, Krista L; Turk, David; Kirbach, Kyleigh; Knobloch, Taylor; Schnitzler, Mark; Qureshi, Kamran; Syn, Wing-Kin; Fleetwood, Vidya A","year":2025,"journal":"Clinical transplantation, 39(10), e70344","doi":"10.1111/ctr.70344","pmid":"41075262","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13957","title":"Stereotactic Body Radiation Therapy Facilitating Debulking Surgery in Metastatic VIPoma with Severe Diarrhea and Hypovolemic Shock.","authors":"Wahab, Ahsan; Raman, Puneet; Koshy, Matthew; Chen, Yolande","year":2025,"journal":"The American journal of case reports, 26, e949041","doi":"10.12659/AJCR.949041","pmid":"40913783","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13958","title":"Pirfenidone alone or combined with either dulaglutide or empagliflozin protects against fructose-induced Parkinsonian features in rats.","authors":"Wahba, Alaa S; Mohamad, Hoda E; Abo-Elmatty, Dina M; Mesbah, Noha M; Wahba, Nehal S; El Azzazy, Ahmed S; Sakr, Amr T","year":2025,"journal":"Behavioural pharmacology, 36(5), 322-336","doi":"10.1097/FBP.0000000000000835","pmid":"40536052","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Rats fed 10% fructose for 24 weeks developed Parkinsonian features: cognitive and motor deficits, loss of substantia nigra neurons, dopamine deficiency, and altered expression of α-synuclein, LRRK2, and parkin. These changes were accompanied by insulin resistance, dyslipidemia, neuroinflammation, and apoptosis.\n\nAll three treatments (dulaglutide 0.2 mg/kg/week SC, empagliflozin 30 mg/kg/day oral, pirfenidone 100 mg/kg/day oral) ameliorated these perturbations when given during the last 4 weeks of the fructose feeding period. Combination therapy (pirfenidone + dulaglutide or pirfenidone + empagliflozin) showed more pronounced effects than individual treatments, demonstrating additive neuroprotection.","whyItMatters":"The link between metabolic disease and neurodegeneration is increasingly recognized, with diabetes patients having elevated Parkinson's disease risk. This study shows that metabolic drugs — particularly the GLP-1 agonist dulaglutide — can protect against diet-induced Parkinsonian changes. This supports the growing interest in repurposing diabetes drugs for neurodegenerative diseases.","specificNumbers":"","methodology":"Rats received 10% fructose in drinking water for 24 weeks to induce metabolic and Parkinsonian features. During the last 4 weeks, different groups received empagliflozin, dulaglutide, pirfenidone, or combinations. Outcomes included behavioral testing (cognitive function and motor coordination), histological examination of substantia nigra neurons, brain biochemistry (dopamine, α-synuclein, LRRK2, parkin), and metabolic parameters (insulin resistance, lipids, inflammation, apoptosis markers).","limitations":"This is a rat study using a fructose-induced model of Parkinsonism, which may not fully replicate human Parkinson's disease (typically caused by complex genetic and environmental factors, not diet alone). The treatment was given concurrently with the last 4 weeks of fructose — essentially a prevention rather than treatment paradigm. Specific quantitative improvements for each treatment and combination were not detailed in the abstract."},{"rthcId":"RPEP-13959","title":"Cardiac care in Duchenne muscular dystrophy.","authors":"Wahbi, Karim","year":2025,"journal":"Archives de pediatrie : organe officiel de la Societe francaise de pediatrie, 32(7S1), 7S20-7S24","doi":"10.1016/S0929-693X(25)00249-0","pmid":"41391906","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13960","title":"Differential risk of systemic complications and mortality in HFrEF and HFpEF patients undergoing total knee arthroplasty: A nationwide propensity matched study with cox regression analysis.","authors":"Wahid, Muaz; Zaidi, Zuhair; Nasser, Elias; Sadek, Ali; Homayoun, Billal; Chen, Antonia; Sambandam, Senthil","year":2025,"journal":"Journal of orthopaedic surgery (Hong Kong), 33(3), 10225536251395952","doi":"10.1177/10225536251395952","pmid":"41187943","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13961","title":"Redox-cleavable disulfide linker enhances siRNA delivery by prodrug-type bifunctional cell-penetrating peptide.","authors":"Wakamori, Keita; Hashikawa, Yuzuki; Urata, Hidehito; Wada, Shun-Ichi","year":2025,"journal":"Bioorganic & medicinal chemistry, 130, 118383","doi":"10.1016/j.bmc.2025.118383","pmid":"40939253","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The researchers developed PI-linker-cRGD, a prodrug-type bifunctional cell-penetrating peptide with a sterically refined redox-cleavable disulfide linker connecting the membrane-penetrating PI peptide to the cancer-targeting cRGD ligand.\n\nThe previous version (PI-cRGD) achieved cellular uptake via endocytosis but failed to deliver siRNA to the cytosol because steric hindrance prevented disulfide bond cleavage inside cells. The redesigned linker solved this problem: it allowed thiol-disulfide exchange at the cell surface, activating the CPP to promote membrane translocation and achieving efficient cytosolic siRNA delivery while maintaining low cytotoxicity and cancer-targeting ability.","whyItMatters":"siRNA therapeutics have enormous potential for treating cancer and genetic diseases by silencing specific genes, but getting them inside cells remains one of the biggest hurdles. Cell-penetrating peptides are a leading delivery strategy, and this work shows that small chemical modifications to the linker connecting functional peptide domains can make the difference between a system that traps cargo in endosomes and one that successfully delivers it to the cytosol where it needs to work.","specificNumbers":"","methodology":"The researchers synthesized a modified bifunctional cell-penetrating peptide with an optimized disulfide linker between the PI (membrane-permeable amphipathic helical peptide containing Aib residues) and cRGD (αvβ3 integrin-targeting) domains. siRNA complexes were formed and tested in cancer cell lines for cellular uptake, cytotoxicity, disulfide cleavage, and cytosolic siRNA delivery efficiency.","limitations":"This was an in vitro study using cancer cell lines only. The efficiency of the disulfide cleavage mechanism in vivo, where the redox environment is more complex, is unknown. Biodistribution, pharmacokinetics, and off-target effects in animal models have not been evaluated. The specific siRNA target and knockdown efficiency were not quantified in the abstract. Scalability of the peptide conjugate synthesis for therapeutic production is not discussed."},{"rthcId":"RPEP-13962","title":"Functional sympatholysis of neuropeptide Y-mediated vasoconstriction in humans.","authors":"Wakeham, Denis J; Hissen, Sarah L; MacNamara, James P; Davis, Scott L; Fadel, Paul J; Levine, Benjamin D; Hearon, Christopher M","year":2025,"journal":"The Journal of physiology, 603(11), 3329-3340","doi":"10.1113/JP288412","pmid":"40448698","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 12 healthy adults during forearm handgrip exercise (15% maximum):\n\n• Phenylephrine (α1-adrenergic) vasoconstriction was attenuated during exercise vs control: ΔFVC -17±9% vs -44±25% (P=0.002), representing 68±18% sympatholysis\n• NPY (Y1 receptor) vasoconstriction was similarly attenuated: ΔFVC -11±7% vs -32±22% (P=0.029), representing 52±34% sympatholysis\n• No significant difference in sympatholysis magnitude between PE and NPY (68% vs 52%, P=0.28)\n\nThis is the first demonstration that NPY-mediated vasoconstriction is sensitive to metabolic inhibition during exercise in humans, confirming that functional sympatholysis extends beyond the classical adrenergic pathway to include the neuropeptide Y system.","whyItMatters":"Understanding how the body balances blood vessel constriction and muscle blood flow during exercise is fundamental to exercise physiology and cardiovascular medicine. NPY is released in large amounts during intense exercise and stress, and its vasoconstriction is more sustained than noradrenaline's. Knowing that the body can override NPY signaling during exercise reassures us that this potent neuropeptide doesn't impair muscle blood flow — and opens questions about conditions where this override might fail.","specificNumbers":"","methodology":"12 healthy adults (7 male, mean age 30, BMI 24.9) underwent brachial artery catheterization for direct intra-arterial drug infusion and blood pressure measurement. Forearm blood flow was measured by Doppler ultrasound. Vasoconstrictor responses to phenylephrine (α1-agonist) and NPY (Y1 receptor agonist) were compared during two conditions: (1) sodium nitroprusside infusion (non-metabolic vasodilatory control) and (2) dynamic rhythmic handgrip exercise at 15% maximal voluntary contraction. Changes in forearm vascular conductance quantified sympatholysis.","limitations":"Small sample size (12 subjects). Only moderate-intensity handgrip exercise was tested (15% MVC); results may differ at higher intensities or with larger muscle groups. The study was conducted in young, healthy adults — functional sympatholysis may be impaired in clinical populations. Intra-arterial drug infusion creates a pharmacological model that may not perfectly replicate endogenous NPY release. The study measured acute effects only."},{"rthcId":"RPEP-13963","title":"Improving chemical synthesis and the antimicrobial activity of human defensins through disulfide bond engineering of HBD-3.","authors":"Walewska, Aleksandra; Kosikowska-Adamus, Paulina; Wardowska, Anna; Bulaj, Grzegorz; Sikorska, Emilia","year":2025,"journal":"Biochimica et biophysica acta. Biomembranes, 1867(8), 184457","doi":"10.1016/j.bbamem.2025.184457","pmid":"40939670","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13964","title":"Amylin: emergent therapeutic opportunities in overweight, obesity and diabetes mellitus.","authors":"Walker, Christopher S; Aitken, Jacqueline F; Vazhoor Amarsingh, Greeshma; Zhang, Shaoping; Cooper, Garth J S","year":2025,"journal":"Nature reviews. Endocrinology, 21(8), 482-494","doi":"10.1038/s41574-025-01125-9","pmid":"40360789","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13965","title":"Prevalence of SGLT2 inhibitor and GLP1 receptor agonist prescriptions in type 2 diabetes patients with and without chronic kidney disease: Analysis of an Australian primary care dataset.","authors":"Wallace, Hannah; Wick, James; Neuen, Brendon L; Buizen, Luke; Badve, Sunil V; Chalmers, John; de Oliveira Costa, Juliana; Falster, Michael O; Ha, Jeffrey T; Jardine, Meg J; Ketema, Daniel Bekele; Lin, Jialing; Nelson, Craig; Pearson, Sallie-Anne; Peiris, David; Rodgers, Anthony; Sasaki, Takaya; Woodward, Mark; Gallagher, Martin; Kotwal, Sradha S; Ronksley, Paul; Jun, Min","year":2025,"journal":"Diabetes, obesity & metabolism, 27(10), 5599-5611","doi":"10.1111/dom.16608","pmid":"40667713","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13966","title":"Trends in Newly Filled GLP-1 Receptor Agonist Prescriptions for US Patients With Versus Without Comorbid Alcohol Use Disorder, 2016-2024.","authors":"Wallach, Joshua D; O'Malley, Stephanie S; Lipska, Kasia J; Ross, Joseph S; Jeffery, Molly M; Savitz, Samuel T","year":2025,"journal":"Journal of addiction medicine","doi":"10.1097/ADM.0000000000001575","pmid":"41036780","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13967","title":"Results of a non-randomized, open-label phase I study evaluating the novel immunomodulatory peptide TCP-25 for treatment of dystrophic epidermolysis bullosa.","authors":"Wallblom, Karl; Holmgren, Katja; Lundgren, Sigrid; Belfrage, Emma; Hoppe, Torborg; Hugerth, Matilda; Lindqvist, Anna-Karin; Sonkoly, Enikö; Schmidtchen, Artur","year":2025,"journal":"Orphanet journal of rare diseases, 21(1), 4","doi":"10.1186/s13023-025-04156-7","pmid":"41327356","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13968","title":"Crafting the future of bone regeneration: the promise of supramolecular peptide nanofiber hydrogels.","authors":"Wan, Longbiao; Yao, Xiaoyue; Pan, Jiali; Xiang, Ziyang; Fu, Dongjie; Ye, Qingsong; Wu, Fei","year":2025,"journal":"Frontiers in bioengineering and biotechnology, 13, 1514318","doi":"10.3389/fbioe.2025.1514318","pmid":"40134775","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13969","title":"Effect of nursing process-based nursing decision implementation on emergency patients with acute ST-segment elevation myocardial infarction.","authors":"Wan, Tiantian; Wang, Caixia; Shi, Jingli; Wu, Shujian","year":2025,"journal":"BMC nursing, 24(1), 125","doi":"10.1186/s12912-025-02698-6","pmid":"39901125","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13970","title":"Chitosan hydrochloride coated and nonionic surfactant modified niosomes: a better way for oral administration of semaglutide.","authors":"Wang, Ben; Su, Zhengxing; Kuang, Meiyan; Luo, Yi; Xu, Minhao; Sun, Meng; Liu, Xingyou; Guo, Yue; Bai, Lu; Wang, Yu; Yan, Xinlei; Xie, Jing; Tang, Yaqin","year":2025,"journal":"Biomedical materials (Bristol, England), 20(3)","doi":"10.1088/1748-605X/adb2cf","pmid":"39908666","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13971","title":"Preparation and characterization of a iRGD-modified recombinant spider silk particles for antitumor polypeptide drug delivery into cancer cells.","authors":"Wang, Ben; Li, Hongbo; Chen, Ying; Chen, Zhi; Li, Pingping; Zhang, Xi; Lin, Xiaoji","year":2025,"journal":"BMC biotechnology, 25(1), 88","doi":"10.1186/s12896-025-01023-y","pmid":"40866866","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13972","title":"Predictor and prognostic modeling in cardiorenal syndrome type 2: a retrospective study of multicenter.","authors":"Wang, Bin; Zheng, Xie; Fu, Qinghui; Luo, Xiaoqian; Pan, Sijun","year":2025,"journal":"Biomarkers in medicine, 19(12), 491-499","doi":"10.1080/17520363.2025.2520738","pmid":"40521649","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13973","title":"Endothelin A receptor in nociceptors is essential for persistent mechanical pain in a chronic pancreatitis of mouse model.","authors":"Wang, Bing; Ge, Jia-Yi; Wu, Jia-Ni; Xu, Jia-Huan; Cao, Xiao-Hua; Chang, Na; Zhou, Xiang; Jing, Peng-Bo; Liu, Xing-Jun; Wu, Yong","year":2025,"journal":"World journal of gastroenterology, 31(23), 103848","doi":"10.3748/wjg.v31.i23.103848","pmid":"40575333","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13974","title":"Semaglutide, a glucagon-like peptide-1 receptor agonist, inhibits oral squamous cell carcinoma growth through P38 MAPK signaling pathway.","authors":"Wang, Can; Wu, Zhengzheng; Zhou, Jiaying; Cheng, Bin; Huang, Yulei","year":2025,"journal":"Journal of cancer research and clinical oncology, 151(3), 103","doi":"10.1007/s00432-025-06154-5","pmid":"40055197","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13975","title":"Potent Inhibition of Human Betacoronaviruses by a Short Double-Stapled Peptide Mimicking the HR2 Core Region in Viral Spike Protein.","authors":"Wang, Chao; Li, Qing; Wang, Yuanzhou; Zhang, Wenpeng; Zheng, Longbo; Tu, Jiahuang; Zhou, Jie; Wang, Fei; Yuan, Yu; Xu, Binbin; Xue, Guangpeng; Du, Xinmeng; Yuan, Ming; Du, Shu; Wang, Huan; Zhuang, Xiaomei; Shi, Weiguo; Lu, Lu; Xiao, Junhai; Wang, Qian; Jiang, Shibo","year":2025,"journal":"Journal of medicinal chemistry, 68(17), 18625-18640","doi":"10.1021/acs.jmedchem.5c01614","pmid":"40844420","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13976","title":"Robinin attenuates cardiac hypertrophy in pulmonary heart disease by modulating SIRT1/NF-κB signaling and inhibiting oxidative stress and the NLRP3 inflammasome.","authors":"Wang, Chao; Qin, Lei; Zhang, Xinrui; Liu, Yubao","year":2025,"journal":"Human & experimental toxicology, 44, 9603271251361892","doi":"10.1177/09603271251361892","pmid":"40679082","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13977","title":"Design, synthesis, and biological evaluation of long-acting glucagon-like peptide-1 (GLP-1) conjugates modified with dual fatty acids and a proline-alanine-serine (PAS) polypeptide.","authors":"Wang, Chengcheng; Zhang, Jinhua; Dong, Yuanzhen; Xu, Jun; Lu, Jianguang; Ding, Chunyong; Cai, Zhengyan; Feng, Jun","year":2025,"journal":"Bioorganic & medicinal chemistry, 128, 118266","doi":"10.1016/j.bmc.2025.118266","pmid":"40499315","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13978","title":"Exploration of the Fasting Hypoglycemic Mechanism of Casein Hydrolysate Enriched with Glu/Gln and Glu/Gln-Containing Peptides in db/db Diabetic-like Mice Using Multiomics Analysis.","authors":"Wang, Chenyang; Xu, Rong; Udenigwe, Chibuike C; Lin, Lianzhu; Zheng, Lin; Zhao, Mouming","year":2025,"journal":"Journal of agricultural and food chemistry, 73(3), 1902-1916","doi":"10.1021/acs.jafc.4c07689","pmid":"39788553","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13979","title":"Generalization of neoantigen-based tumor vaccine by delivering peptide-MHC complex via oncolytic virus.","authors":"Wang, Chenyi; Shi, Yingjun; Zhang, Da; Sun, Yupeng; Xie, Junjie; Wu, Bingchen; Zhang, Cuilin; Liu, Xiaolong","year":2025,"journal":"EMBO molecular medicine, 17(5), 1118-1152","doi":"10.1038/s44321-025-00225-3","pmid":"40195559","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13980","title":"Nuezhenide of the fruits of Nuzhenzi (Ligustrum lucidum Ait.) is a functional analog of ghrelin.","authors":"Wang, Chia-Hao; Tseng, Ching-Yu; Hsu, Wei-Li; Tzen, Jason T C","year":2025,"journal":"Journal of ethnopharmacology, 339, 119108","doi":"10.1016/j.jep.2024.119108","pmid":"39566863","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13981","title":"Harnessing multifunctional HBc virus-like particles for safe and effective delivery of melittin in cancer therapy.","authors":"Wang, Chufan; Zhang, Fengrui; Tang, Haobo; Su, Zhengchan; Duan, Yufei; Feng, Wei; Lin, Xiaoning; Chen, E; Wang, Xiumin; Ren, Lei","year":2025,"journal":"Nanomedicine (London, England), 20(14), 1661-1675","doi":"10.1080/17435889.2025.2528591","pmid":"40616815","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13982","title":"Bioinspired Co-Assembled Hydrogels Constructed from Marine Self-Assembling Peptides and Polyphenol Network: Antioxidant and Infected Wound Healing.","authors":"Wang, Chuhan; Yu, Dingyi; Liu, Wen; Zhu, Xiang; Zhang, Hanzhe; Zheng, Shuang; Chen, Jingdi","year":2025,"journal":"Antioxidants (Basel, Switzerland), 14(7)","doi":"10.3390/antiox14070785","pmid":"40722889","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The PTDP hydrogel demonstrated multiple therapeutic properties in a single material. In vitro, it showed potent antioxidant activity, efficiently inhibited both Staphylococcus aureus and Escherichia coli growth, and was compatible with endothelial cells — even promoting their migration and proliferation.\n\nIn murine full-thickness infected wound models, the hydrogel significantly accelerated wound closure, enhanced neovascularization (new blood vessel formation), and improved collagen deposition. The material's physicochemical properties were also notable: tunable plasticity, high swelling ratios for absorbing wound exudate, sustained hydration retention, and strong substrate adhesion — all important qualities for a practical wound dressing.","whyItMatters":"Infected wounds — particularly chronic ones — remain a major clinical challenge, especially in patients with diabetes or compromised immune systems. Current wound dressings often address only one problem (infection OR inflammation OR tissue regeneration). This multifunctional hydrogel tackles all three simultaneously: killing bacteria, reducing oxidative damage, and actively promoting tissue repair. The use of marine-derived peptides also represents a growing trend of looking to ocean organisms for biomedical materials.","specificNumbers":"","methodology":"The researchers developed the PTDP hydrogel through in situ freeze-thaw co-assembly of four components: polyvinyl alcohol (PVA) as a structural base, tea polyphenols (TP) for antioxidant activity, polydopamine (PDA) for adhesion and antimicrobial effects, and marine-derived self-assembling peptides (AAPs) for tissue regeneration. The material was characterized for mechanical and physicochemical properties. In vitro testing assessed antioxidant activity, antibacterial efficacy against S. aureus and E. coli, and cytocompatibility with endothelial cells. In vivo testing used full-thickness infected wound models in mice.","limitations":"This is a preclinical study tested only in mice. Full-thickness wound models in mice heal differently from human wounds (mice heal largely by contraction, while humans heal by re-epithelialization). Specific quantitative data on wound closure rates, bacterial reduction percentages, and mechanical properties were not provided in the abstract. The long-term biocompatibility and degradation profile of the hydrogel were not discussed. Manufacturing scalability and cost were not addressed."},{"rthcId":"RPEP-13983","title":"Current progress and remaining challenges of peptide-drug conjugates (PDCs): next generation of antibody-drug conjugates (ADCs)?","authors":"Wang, Dongyuan; Yin, Feng; Li, Zigang; Zhang, Yu; Shi, Chen","year":2025,"journal":"Journal of nanobiotechnology, 23(1), 305","doi":"10.1186/s12951-025-03277-2","pmid":"40259322","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"PDCs offer several advantages over ADCs: more accessible industrial synthesis, versatile functionalization, high tissue penetration, rapid clearance, and low immunotoxicity. Three peptide categories serve different delivery functions — tumor-targeting peptides for specificity, cell-penetrating peptides for intracellular delivery, and self-assembling peptides for controlled release and nanostructure formation. PDCs can overcome drug resistance, control drug release, and improve efficacy while reducing off-target toxicity. However, poor pharmacokinetic properties and low bioactivity remain the primary clinical development challenges.","whyItMatters":"ADCs represent a multi-billion-dollar cancer drug market, but their large antibody size limits tissue penetration and manufacturing is complex and expensive. If PDCs can overcome their current pharmacokinetic limitations, they could democratize targeted cancer therapy — being cheaper to produce, easier to modify, and capable of reaching tumors that antibodies cannot. With several PDCs now in clinical trials, this technology is approaching real-world clinical impact.","specificNumbers":"","methodology":"Comprehensive narrative review analyzing PDC design principles (informed by ADC success factors), component functions (peptides, linkers, payloads), peptide categories, pharmacokinetics, and current clinical trial landscape. The review draws comparisons between PDCs and established ADC technology throughout.","limitations":"As a narrative review, this does not include systematic methodology or meta-analysis. The comparison between PDCs and ADCs is partially theoretical — very few PDCs have completed late-stage clinical trials, so the real-world performance gap remains uncertain. The challenges highlighted (pharmacokinetics, bioactivity) are significant and may limit which tumor types PDCs can effectively treat. Self-assembling peptide systems are particularly early in development."},{"rthcId":"RPEP-13984","title":"Tirzepatide mitigates Stroke-Induced Blood-Brain barrier disruption by modulating Claudin-1 and C/EBP-α pathways.","authors":"Wang, Duozi; Wang, Jianhong; Li, Binghu; Yang, Shu; Guo, Fuqiang; Zheng, Bo; Wang, Jian","year":2025,"journal":"Molecular medicine (Cambridge, Mass.), 31(1), 263","doi":"10.1186/s10020-025-01312-4","pmid":"40702450","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13985","title":"Pharmacokinetic Characteristics of a Once-Weekly Combination Therapy of Insulin Icodec and Semaglutide Versus Its Separate Components in Chinese Individuals with Type 2 Diabetes.","authors":"Wang, Fangfang; Luan, Zijian; Maltesen, Raluca; Reenberg, Asbjørn T; Westergaard, Lisbet; Liu, Dongyang","year":2025,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 16(11), 2213-2225","doi":"10.1007/s13300-025-01803-x","pmid":"41051695","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13986","title":"Impact of liraglutide on albumin-to-creatinine ratio in type 2 diabetes mellitus: a meta-analysis.","authors":"Wang, Feng; Xu, Guangzhong; Feng, Wei; Qu, Gengbao; Li, Pengyu; Li, Kai","year":2025,"journal":"European journal of medical research, 30(1), 652","doi":"10.1186/s40001-025-02801-2","pmid":"40696486","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across seven RCTs involving 473 participants, liraglutide significantly reduced the albumin-to-creatinine ratio compared to controls (weighted mean difference: -11.76 mg/g, 95% CI -21.71 to -1.81, P = 0.02). Heterogeneity was substantial (I² = 75%).\n\nSubgroup analyses identified populations with the greatest benefit: patients with HbA1c > 8.0%, treatment duration > 12 weeks, and age < 60 years all showed significant ACR reductions. Meta-regression found that no single variable (sample size, HbA1c, baseline ACR, duration, or dose) explained the heterogeneity. Sensitivity analysis confirmed stable results, and no publication bias was detected (Begg's P = 0.46, Egger's P = 0.57).","whyItMatters":"Diabetic kidney disease is the leading cause of kidney failure worldwide, and early kidney damage is detected by elevated ACR — often before patients have any symptoms. This meta-analysis provides pooled evidence from the highest-quality study type (RCTs) that liraglutide protects kidneys in type 2 diabetes beyond what might be expected from blood sugar control alone. This supports using liraglutide as a dual-benefit therapy for diabetes patients at risk of kidney complications.","specificNumbers":"","methodology":"This systematic review and meta-analysis searched PubMed, Embase, Cochrane Library, WanFang, and CNKI databases through November 2024 for randomized controlled trials comparing liraglutide to controls (placebo or active drugs) in type 2 diabetes patients, with ACR as an outcome. Seven RCTs with 473 participants met inclusion criteria. Data were pooled using random-effects models due to heterogeneity. Subgroup analyses, meta-regression, sensitivity analyses, and publication bias assessments (Begg's and Egger's tests) were performed. The review was registered on PROSPERO.","limitations":"The meta-analysis included only 7 trials with 473 participants — a relatively small evidence base. The substantial heterogeneity (I² = 75%) suggests meaningful differences between studies that random-effects models may not fully address. The included trials varied in design, comparators, and patient populations. Meta-regression could not identify the source of heterogeneity. The ACR is a surrogate endpoint — longer-term studies examining hard kidney outcomes (dialysis, transplant) would be more definitive."},{"rthcId":"RPEP-13987","title":"Novel therapeutic insights into pathological cardiac hypertrophy: tRF-16-R29P4PE regulates PACE4 and metabolic pathways.","authors":"Wang, Feng; Li, Ping; Yan, Xinxin; Yue, Anna; Xu, Jingyi; Shao, Yaqing; Zhang, Kaiyu; Zhang, Qian; Li, Yuan; Sun, Kangyun","year":2025,"journal":"Biochimica et biophysica acta. Molecular cell research, 1872(3), 119920","doi":"10.1016/j.bbamcr.2025.119920","pmid":"39947523","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13988","title":"Ultrasonic Bone Scalpel vs Turbine Drill in Mandibular Third Molar Extraction: Impact on Postoperative Pain and Inflammation.","authors":"Wang, Ge; Wang, Hui; Xu, Jie; Zhang, Xiaoyan","year":2025,"journal":"Journal of pain research, 18, 4029-4036","doi":"10.2147/JPR.S534667","pmid":"40822433","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13989","title":"The novel cathelicidin-DM antimicrobial peptide conjugated carbomer and thermosensitive chitosan hydrogel speeds up wound-healing in both non-infected and S. aureus-infected wounds.","authors":"Wang, Guixi; Huang, Yafei; Shi, Yaoqiang; Han, Qinqin; Zhang, Jinyang; Song, Yuzhu; Li, Chao","year":2025,"journal":"International journal of biological macromolecules, 288, 138659","doi":"10.1016/j.ijbiomac.2024.138659","pmid":"39667454","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Researchers developed two hydrogel formulations (carbomer-based and temperature-sensitive chitosan-based) loaded with the antimicrobial peptide cathelicidin-DM, originally isolated from a toad species. Both hydrogels significantly accelerated healing of full-thickness skin wounds in mice — in both infected (S. aureus) and non-infected wounds. The peptide interacted with both hydrogel materials at the molecular level, forming 3D network structures with favorable properties. The hydrogels also demonstrated hemostatic (bleeding-stopping) capabilities.","whyItMatters":"Chronic wound infections complicated by antibiotic-resistant bacteria are a growing healthcare crisis. Combining an antimicrobial peptide with practical wound dressing materials (hydrogels) solves two key problems simultaneously: killing drug-resistant bacteria and accelerating tissue repair, while protecting the peptide from degradation.","specificNumbers":"Broad-spectrum against MDR bacteria · full-thickness wound healing in mice · effective in both infected and non-infected wounds · hemostatic capability · 2 hydrogel formulations","methodology":"Cathelicidin-DM peptide was conjugated with carbomer and thermosensitive chitosan to create two hydrogel formulations. Material properties (3D structure, rheology, molecular interactions) were characterized. In vivo testing used mouse models with full-thickness skin wounds, both clean and S. aureus-infected, comparing hydrogel-treated versus control wounds for healing speed and hemostatic ability.","limitations":"Tested only in mice with acute wound models — chronic human wounds involve different healing dynamics. Specific healing metrics and timeframes are not detailed in the abstract. Long-term stability and shelf life of the peptide-loaded hydrogels were not addressed. Regulatory pathway for peptide-hydrogel combination products would be complex."},{"rthcId":"RPEP-13990","title":"Glucagon-like peptide-1 receptor agonist in large vessel occlusion treated by reperfusion therapy-a phase 2 randomized trial.","authors":"Wang, Hao; Ko, Ho; Leung, Thomas W; Huang, Junzhe; Sai, Junjie; Liang, Yu; Li, Haipeng; Zhang, Jie; Cao, Qingyang; Zang, Wentao; Li, Yinfei; Ma, Sze Ho; Lui, Wai Ting; Choi, Joseph; Chan, Charlie; Wong, Jason; Kwok, Andrew J; Ma, Karen; Fan, Florence; Chan, Anne; Ip, Vincent; Leung, Howan; Soo, Yannie; Wong, Ka Tak; Lai, Billy; Chu, C M; Leung, Ho Sang; Hui, Anselm; Cheung, Tom; Abrigo, Jill; Li, Siu Hung; Chan, Larry; Yeung, Jonas; Pan, Sangqi; Yip, Terry; Lui, L T; Hung, Trista; Tsang, Suk Fung; Leng, Xinyi; Lam, Bonnie; Mok, Vincent C T; Chan, Rosa H M; Nguyen, Thanh N; Hu, Wei; Che, Fengyuan; Ip, Bonaventure Y","year":2025,"journal":"Nature communications, 16(1), 11274","doi":"10.1038/s41467-025-66167-z","pmid":"41392086","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13991","title":"Nanoparticle-Driven Tendon Repair: Role of Vasoactive Intestinal Peptide in Immune Modulation and Stem Cell Enhancement.","authors":"Wang, Hao; Gao, Yucheng; Wang, Jinyu; Cao, Mumin; Dai, Guangchun; Lu, Panpan; Sheng, Renwang; Zhang, Cheng; Wang, Qianqian; Li, Gang; Ai, Qi Yong H; Rui, Yunfeng; Shi, Liu","year":2025,"journal":"ACS nano, 19(14), 13871-13888","doi":"10.1021/acsnano.4c16917","pmid":"40184556","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13992","title":"Advances in the pathogenesis of rosacea.","authors":"Wang, Hui; Zhou, Cheng","year":2025,"journal":"Frontiers in immunology, 16, 1705588","doi":"10.3389/fimmu.2025.1705588","pmid":"41646975","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13993","title":"Screening of an antimicrobial peptide-TWPAL and its application in hydrogels for wound healing.","authors":"Wang, Huinan; Gao, Fengyuan; Rafiq, Muhammad; Yu, Bing; Niu, Qinghai; Cong, Hailin","year":2025,"journal":"Journal of materials chemistry. B, 13(7), 2418-2430","doi":"10.1039/d4tb02253j","pmid":"39813073","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13994","title":"Molecular imaging of neuroendocrine tumors: Current applications and future trends.","authors":"Wang, Ivan E; SaTsu, Helen A; Brooks, Allen F; Werner, Rudolf A; Rowe, Steven P; Scott, Peter J H; Viglianti, Benjamin L","year":2025,"journal":"Diagnostic and interventional imaging, 106(11), 385-393","doi":"10.1016/j.diii.2025.05.005","pmid":"40404554","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13995","title":"Dynamic multi-omics profiling of islet and gut hormonal secretion and peripheral crosstalk in response to various nutrient loads.","authors":"Wang, Jiachen; Liu, Ling; Liu, Hechun; Qian, Yu; Zhang, Sijie; Zheng, Shuai; Jiang, Hemin; Zhou, Yue; Cheng, Xiaoliang; Fu, Qi; Dai, Hao; Yang, Tao","year":2025,"journal":"Cell reports. Medicine, 6(9), 102327","doi":"10.1016/j.xcrm.2025.102327","pmid":"40907494","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The study revealed several important findings about peptide hormone dynamics:\n\n- GLP-1 and GIP secretion patterns are exclusively explained by postprandial (after-eating) data — fasting measurements miss them entirely\n- Postprandial multi-omics data significantly improved the ability to explain insulin and glucagon secretion patterns compared to fasting data alone\n- Hormone secretion and molecular responses showed substantial heterogeneity among macronutrient types (mixed meals vs. four distinct macronutrient loads)\n- Protein load showed the strongest association with both hepatic (liver) and muscular insulin resistance\n- Butter load connected most strongly with systemic insulin resistance\n- Postprandial multi-omics better predicted insulin resistance than fasting data, with hepatic enrichment\n- Several molecules were identified that mediate interactions between insulin resistance and islet α-cell (glucagon) and β-cell (insulin) function","whyItMatters":"GLP-1 and GIP are the targets of the most successful new drugs in metabolic medicine (semaglutide, tirzepatide). Understanding how these peptide hormones naturally respond to different foods — and how their responses connect to insulin resistance — is critical for both drug development and nutrition-based interventions. This study provides the most comprehensive postprandial peptide hormone map to date, potentially enabling precision nutrition approaches for diabetes prevention.","specificNumbers":"","methodology":"This was a human multi-omics study where participants consumed mixed meals and four distinct macronutrient loads. Dynamic postprandial measurements included islet hormones (insulin, glucagon), gut hormones (GLP-1, GIP), and comprehensive multi-omics profiling (likely proteomics, metabolomics, and/or lipidomics). Data were analyzed to characterize hormone secretion patterns, identify responsive molecular networks, and assess relationships with peripheral insulin resistance (hepatic, muscular, and systemic).","limitations":"The abstract does not specify the number of participants or their characteristics (healthy vs. metabolic disease). The multi-omics approach generates large datasets that require careful statistical handling to avoid false discoveries. The macronutrient loads were individual nutrients, which may not reflect how hormones respond to real-world mixed meals. Cross-sectional associations between hormone patterns and insulin resistance don't prove causation."},{"rthcId":"RPEP-13996","title":"Exploring the Efficacy and Safety of Tirzepatide in Obesity Management and Cardiometabolic Risk Factors: A Comprehensive Systematic Review and Meta-Analysis.","authors":"Wang, Jian-Ying; Kang, Jyun-Wei; Peng, Tzu-Rong; Chen, Hsin-Yen; Chen, Shih-Ming; Lee, Ming-Chia","year":2025,"journal":"Clinical obesity, 15(6), e70036","doi":"10.1111/cob.70036","pmid":"40685889","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 10 RCTs with 6,257 participants, tirzepatide produced a pooled mean weight reduction of -11.62 kg compared to placebo (95% CI: -14.24 to -9.01, p < 0.001).\n\nAt the highest dose of 15 mg, weight loss milestones were impressive: 88.1% achieved >5% weight loss, 63.3% achieved >10%, and 51.8% achieved >15%. Significant improvements were observed across cardiometabolic markers including HbA1c, waist circumference, BMI, and lipid profiles. The safety profile was favorable with no increase in serious adverse events or mortality.","whyItMatters":"This comprehensive meta-analysis provides the strongest pooled evidence to date for tirzepatide's effectiveness in obesity management. The finding that over half of patients on the highest dose lose more than 15% of their body weight — approaching surgical levels of weight loss — positions tirzepatide as a potentially transformative non-surgical obesity treatment.","specificNumbers":"","methodology":"Systematic review and meta-analysis following PRISMA guidelines. Researchers searched PubMed, Cochrane Library, and EMBASE through December 2024 for randomized controlled trials comparing tirzepatide to placebo in adults with obesity, with or without type 2 diabetes. Ten RCTs met inclusion criteria. Pooled analyses calculated mean differences for weight and cardiometabolic outcomes.","limitations":"The meta-analysis included trials with varying durations and populations (with and without type 2 diabetes), which introduces heterogeneity. Long-term safety and efficacy beyond the trial periods are not established. Publication bias cannot be fully excluded. The analysis compared tirzepatide to placebo only, not to active comparators like semaglutide. Weight regain after discontinuation was not assessed."},{"rthcId":"RPEP-13997","title":"Tirzepatide Induces Ferroptosis in Glioblastoma Cell Lines via the SOX2/SLC7A11 Axis: A Potential Therapeutic Strategy for Glioma Treatment.","authors":"Wang, Jiangtao; Chen, Hang; Wang, Xinjun","year":2025,"journal":"Journal of biochemical and molecular toxicology, 39(8), e70392","doi":"10.1002/jbt.70392","pmid":"40678831","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13998","title":"Maternal Supplementation of Collagen Peptide Chelated Trace Elements Enhances Skeletal Muscle Development in Chicks.","authors":"Wang, Jiao; Huang, Zhenwu; Li, Simeng; Lv, Zengpeng","year":2025,"journal":"Biological trace element research, 203(7), 3860-3869","doi":"10.1007/s12011-024-04430-y","pmid":"39477850","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-13999","title":"Risk factors for hepatocellular carcinoma: an umbrella review of systematic review and meta-analysis.","authors":"Wang, Jie; Qiu, Kaijie; Zhou, Songsheng; Gan, Yichao; Jiang, Keting; Wang, Donghuan; Wang, Haibiao","year":2025,"journal":"Annals of medicine, 57(1), 2455539","doi":"10.1080/07853890.2025.2455539","pmid":"39834076","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14000","title":"Dual-functional pH-sensitive nanoliposomes modified with CD47 mimicry peptide enhance icariin delivery to attenuate neuroinflammation and oxidative stress in epilepsy.","authors":"Wang, Jing; Du, Yangsa; Su, Guoting; Tang, Weiting; Long, Xiaoyan; He, Yongju; Feng, Li","year":2025,"journal":"Materials today. Bio, 35, 102528","doi":"10.1016/j.mtbio.2025.102528","pmid":"41322155","tags":["peptide-drug-delivery","neurological-disease"],"studyType":"animal-and-cell","evidenceStrength":"preliminary","keyFinding":"Researchers designed a dual-function nanoliposome system for epilepsy treatment that uses a CD47 mimicry peptide to evade immune clearance and pH sensitivity to target epileptic brain regions. The CD47 peptide coating signals macrophages with a 'don't eat me' message, preventing immune cells from destroying the nanoparticles and enabling prolonged circulation. Because epileptic foci have an acidic microenvironment, the pH-sensitive liposomes preferentially release their drug cargo at the disease site.\n\nThe system successfully delivered icariin (a plant-derived anti-inflammatory compound) to epileptic brain tissue in mice, significantly alleviating neuronal damage, reducing neuroinflammation and oxidative stress, and improving cognitive dysfunction. Network pharmacology and transcriptomics confirmed the therapeutic mechanism.","whyItMatters":"About 30% of epilepsy patients don't respond to existing seizure medications — a condition called refractory epilepsy. Neuroinflammation and oxidative stress drive disease progression in these patients, but getting anti-inflammatory drugs across the blood-brain barrier and to the right brain regions is extremely difficult. The CD47 mimicry peptide solves the immune clearance problem (extending circulation time), while pH sensitivity solves the targeting problem (releasing drug at acidic epileptic foci). This combined approach could deliver drugs to the brain more effectively than conventional methods.","specificNumbers":"~30% of epilepsy patients refractory to current ASMs · CD47 mimicry peptide: reduces macrophage phagocytosis · pH-sensitive release at epileptic foci · prolonged circulation · alleviated neuronal damage and cognitive dysfunction in mice","methodology":"Researchers created pH-sensitive nanoliposomes modified with CD47 mimicry peptide and loaded with icariin (ICA@LipD-CD47). Network pharmacology predicted ICA's therapeutic targets for epilepsy. Animal experiments in epileptic mice evaluated brain targeting, neuroprotection, cognitive function, and neuroinflammation markers. Transcriptomics analysis confirmed the anti-inflammatory and antioxidant mechanisms of action.","limitations":"This is a preclinical mouse study with no human data. The epilepsy model used may not represent all forms of human refractory epilepsy. Icariin (the drug cargo) is a natural compound with limited clinical evidence for epilepsy in humans. The manufacturing complexity of peptide-modified pH-sensitive nanoliposomes presents scale-up challenges. Long-term safety of repeated brain-targeted nanoparticle delivery is unknown."},{"rthcId":"RPEP-14001","title":"Machine learning algorithms to predict heart failure with preserved ejection fraction among patients with premature myocardial infarction.","authors":"Wang, Jing-Xian; Li, Chang-Ping; Cui, Zhuang; Liang, Yan; Wang, Yu-Hang; Zhou, Yu; Liu, Yin; Gao, Jing","year":2025,"journal":"Frontiers in cardiovascular medicine, 12, 1571185","doi":"10.3389/fcvm.2025.1571185","pmid":"40401222","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14002","title":"Cultured Chinese Giant Salamander Skin and Skin Secretions as a Source of Bioactive Peptides for Food and Medicine.","authors":"Wang, Jinghua; Liu, Yuchen; Guo, Hongfei; Chen, Dejing; Abdu, Hassan Idris; Yang, Meng; Pei, Jinjin; El-Aty, A M Abd","year":2025,"journal":"Food science of animal resources, 45(1), 109-125","doi":"10.5851/kosfa.2024.e114","pmid":"39840243","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Giant salamander skin and secretions contain multiple families of bioactive peptides including brevinins, bombesins, dermaseptins, esculentins, magainins, temporins, tigerinins, and salamandrins. These peptides collectively demonstrate antioxidant, antimicrobial, anticancer, and antidiabetic biological activities.\n\nThe review identifies potential applications across two industries: food (as multifunctional additives and dietary supplements) and biomedicine (as antimicrobial agents, anticancer leads, and drug delivery vehicles). The nutritional composition of giant salamanders and the production status of cultured specimens are also examined as context for sustainable sourcing.","whyItMatters":"The discovery of bioactive peptides in animal by-products represents a growing area of sustainable biotechnology — turning waste into valuable products. Amphibian skin peptides are already recognized as one of nature's richest sources of antimicrobial compounds, evolved over hundreds of millions of years. Giant salamanders are increasingly farmed in China, creating a consistent supply of skin waste that could be valorized. Several of these peptide families (magainins, dermaseptins) have analogs being developed as pharmaceutical candidates.","specificNumbers":"","methodology":"This is a comprehensive narrative review analyzing published literature on bioactive peptides derived from Chinese giant salamander (Andrias davidianus) skin and secretions. The authors compiled data on peptide identification, biological activities, nutritional composition, aquaculture production status, and potential commercial applications.","limitations":"This is a review paper that compiles existing research without generating new data. Most biological activities of these peptides have been demonstrated only in laboratory settings (in vitro), with limited or no in vivo animal studies or human clinical trials. The scalability of peptide extraction from salamander skin for commercial applications has not been demonstrated. Potential toxicity and allergenicity of these peptides in food or pharmaceutical applications have not been thoroughly evaluated."},{"rthcId":"RPEP-14003","title":"Safety, Tolerability, and Pharmacokinetics of Galcanezumab, an Anti-CGRP Antibody, in Healthy Chinese Participants.","authors":"Wang, Jingjing; Li, Nanyang; He, Jinjie; Zhang, Jing; Wang, Lili; Kielbasa, William; Qian, Chenxi; Zhang, Yanjie; Wang, Liang","year":2025,"journal":"Clinical pharmacology in drug development, 14(12), 918-924","doi":"10.1002/cpdd.1599","pmid":"40939150","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14004","title":"Glucagon-like peptide-1 receptor agonist treatment associated weight fluctuation and influencing factors in patients with overweight or obesity.","authors":"Wang, Jingxuan; Lin, Chu; Cai, Xiaoling; Wang, Yiran; Wei, Tingyang; Wang, Yuan; Tie, Changjie; Yang, Yuteng; Lv, Fang; Yang, Wenjia; Ji, Linong","year":2025,"journal":"Diabetes, obesity & metabolism, 27(9), 5042-5051","doi":"10.1111/dom.16552","pmid":"40629903","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14005","title":"LL37-DNA Complex Drives Vitiligo Progression Through TLR9-MyD88 Signaling Pathways.","authors":"Wang, Jingying; Mao, Hanxiao; Liu, Rulan; Zeng, Ziyuan; Xie, Lvsha; Yang, Yan; He, Yuanmin","year":2025,"journal":"Pigment cell & melanoma research, 38(1), e13202","doi":"10.1111/pcmr.13202","pmid":"39344705","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The antimicrobial peptide LL37 was found at elevated levels in vitiligo patients' blood and skin lesions. When keratinocytes (skin cells) were exposed to oxidative stress (H2O2), they released LL37, which then bound to DNA forming LL37-DNA complexes. These complexes activated the TLR9-MyD88 signaling pathway in keratinocytes, increasing secretion of chemokines CXCL9, CXCL10, and CXCL16, which in turn attracted CD8+ T cells — the immune cells that destroy melanocytes in vitiligo.\n\nThis establishes a mechanistic pathway: oxidative stress → LL37 release → DNA binding → TLR9 signaling → immune cell recruitment → melanocyte destruction.","whyItMatters":"Vitiligo affects millions of people worldwide, and understanding what triggers the immune system to attack pigment-producing cells is essential for developing targeted treatments. By identifying LL37 as a key early player in this autoimmune cascade, this study reveals a potential therapeutic target — blocking LL37 or its downstream signaling could potentially slow or prevent vitiligo progression.","specificNumbers":"","methodology":"Researchers measured LL37 levels in serum and skin lesions from vitiligo patients. They then used cell culture experiments to show that oxidative stress (H2O2) causes keratinocytes to release LL37, that LL37-DNA complexes activate TLR9-MyD88 signaling, and that the resulting chemokine secretion drives CD8+ T cell migration toward melanocytes.","limitations":"This is primarily a cell culture study supplemented with patient tissue analysis. The mechanistic pathway was demonstrated in vitro and may not fully capture the complexity of vitiligo progression in living patients. No therapeutic intervention was tested. The study does not quantify the exact contribution of LL37 relative to other inflammatory factors in vitiligo."},{"rthcId":"RPEP-14006","title":"The Cardiac and Renal Safety of Semaglutide in Patients with Type 2 Diabetes: A Real-World Study Based on FAERS.","authors":"Wang, Jingyu; Xie, Tong; Zhang, Yuemiao; Zhang, Hong","year":2025,"journal":"Cardiorenal medicine, 15(1), 413-422","doi":"10.1159/000546238","pmid":"40349689","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14007","title":"Pre-pregnancy treatment of semaglutide improves high-fat-diet-induced placental and fetal hypothalamic alterations in a sex-specific manner in rats†.","authors":"Wang, Jingyue; Wang, Ning; Guo, Haonan; Niu, Xinyi; Hu, Shuyuan; Pan, Xingyan; Wang, Mingxi; Zhang, Duowen; Song, Lin; Sun, Bo","year":2025,"journal":"Biology of reproduction, 113(6), 1463-1474","doi":"10.1093/biolre/ioaf178","pmid":"40794822","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14008","title":"Lacticaseibacillus rhamnosus OF44 with Potent Antimicrobial Activity: Evidence from the Complete Genome and Phenotypic Analysis.","authors":"Wang, Jinhong; Ma, Zhihui; Xu, Qianyue; Wei, Benliang; Wang, Mengmeng; Liu, Yanhong; Tian, Yu; Zhang, Haifeng; Xiao, Liang; Zhong, Yiyi; Zou, Yuanqiang","year":2025,"journal":"Probiotics and antimicrobial proteins","doi":"10.1007/s12602-025-10515-4","pmid":"40106191","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14009","title":"Characterization of two novel angiotensin converting enzyme-inhibitory peptides from yellow tuna peptides: Inhibitory mechanism, transport route and network pharmacology analysis.","authors":"Wang, Jinxin; Guo, Si-Jie; Xie, Xing; Ma, Tian-Xin; Wen, Qin-Hui; Gao, Yong-Lin; Li, Yueming; Zhang, Jian; Li, Wenjun; Zhang, Lu","year":2025,"journal":"Food research international (Ottawa, Ont.), 209, 116232","doi":"10.1016/j.foodres.2025.116232","pmid":"40253180","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14010","title":"Cardiometabolic risk effects of weight-loss medications: An updated network meta-analysis.","authors":"Wang, Juan; Diao, Houze; Sun, Wenhui; Huan, Wenru; Wang, Yating; Ding, Liyi; Cui, Weiwei; Ma, Ke","year":2025,"journal":"Diabetes, obesity & metabolism, 27(9), 5311-5321","doi":"10.1111/dom.16585","pmid":"40600452","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14011","title":"LC-AMP-I1, a novel venom-derived antimicrobial peptide from the wolf spider Lycosa coelestis.","authors":"Wang, Junyao; Liu, Xi; Song, Yuxin; Liu, Zhonghua; Tang, Xing; Tan, Huaxin","year":2025,"journal":"Antimicrobial agents and chemotherapy, 69(1), e0042424","doi":"10.1128/aac.00424-24","pmid":"39620694","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14012","title":"Analyses of Off-Target Effects on Cardiac and Skeletal Muscles by Berberine, a Drug Used to Treat Cancers and Induce Weight Loss.","authors":"Wang, Jushuo; Fan, Yingli; Dube, Syamalima; Benz, Patricia; Dube, Dipak; Sanger, Jean M; Sanger, Joseph W","year":2025,"journal":"Cytoskeleton (Hoboken, N.J.), 82(6), 344-359","doi":"10.1002/cm.21950","pmid":"39526308","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Berberine inhibited myofibril assembly at the nascent myofibril stage in embryonic skeletal muscle cells, preventing the normal progression to mature muscle fibers. RT-PCR experiments showed that berberine specifically inhibited mRNA for muscle myosin II heavy chains (a key structural protein) while not affecting muscle actin mRNA in skeletal muscle cells.\n\nImportantly, berberine had no effect on myofibril assembly in embryonic heart cells, which may explain clinical reports of berberine being safe for the heart even in cancer patients. In contrast, semaglutide showed no effects on myofibril assembly in either cardiac or skeletal muscle cell cultures, suggesting a cleaner muscle safety profile.","whyItMatters":"Berberine has surged in popularity as an affordable alternative to prescription GLP-1 drugs for weight loss, marketed widely on social media. However, its effects on muscle tissue have received little attention. This study is the first to directly compare berberine and semaglutide for muscle cell effects, revealing that berberine — but not semaglutide — disrupts skeletal muscle development. Given widespread concerns about muscle loss during weight loss (sarcopenic obesity), this finding is clinically relevant.","specificNumbers":"","methodology":"Researchers used cultured embryonic cardiac and skeletal muscle cells as a preclinical assay system. Cells were exposed to berberine (a UHRF1 ligase inhibitor) and assessed for myofibril assembly progression through three established stages: premyofibrils, nascent myofibrils, and mature myofibrils. Semaglutide was tested in the same culture system as a comparison. RT-PCR was used to measure effects on muscle protein gene expression. The study builds on the laboratory's established three-step model of myofibrillogenesis.","limitations":"This is an in vitro cell culture study using embryonic muscle cells, which may not directly reflect what happens in adult human muscles. The concentrations of berberine used in culture may not match physiological levels achieved through oral supplementation. No animal or human data on berberine's effects on mature muscle tissue were presented. The study does not address whether berberine-induced muscle effects would be clinically significant at typical supplement doses or whether they would be reversible."},{"rthcId":"RPEP-14013","title":"Changes of low-abundance peptides in frozen orange juice before and after frozen storage and pasteurization processing, and their contribution to ACE inhibition activity.","authors":"Wang, Kewen; Zhu, Xiangyang; Liao, Xiaojun; Xu, Zhenzhen","year":2025,"journal":"Food research international (Ottawa, Ont.), 202, 115739","doi":"10.1016/j.foodres.2025.115739","pmid":"39967106","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14014","title":"Overview of Peptides and Their Potential Roles in Skin Health and Beauty.","authors":"Wang, Leyang; Wu, Zhijing; Wang, Xinyu; Wang, Xiaoli; Mao, Jingzhuo; Yan, Yan; Zhang, Lu; Zhang, Zhuzhen","year":2025,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 31(2), e3668","doi":"10.1002/psc.3668","pmid":"39777813","tags":["cosmetic-peptides","skin-health"],"studyType":"review","evidenceStrength":"expert-review","keyFinding":"Peptides have become major ingredients in the cosmetic and skincare industry due to their potential to boost skin health. This comprehensive review covers peptides from four angles: their sources (natural and synthetic), their biological functions, their specific applications in cosmetics and skincare, and the delivery technologies needed to get them into the skin effectively.\n\nThe review contextualizes cosmetic peptides within the broader peptide landscape, noting that over 80 peptide-based drugs have reached the market for conditions ranging from diabetes to cardiovascular disease. Peptides in skincare work through multiple mechanisms including signaling collagen production, inhibiting neurotransmitter release (Botox-like effects), carrying metals like copper to skin cells, and inhibiting enzymes that break down collagen and elastin.","whyItMatters":"The cosmetic peptide market is rapidly growing, but consumers and even dermatologists often struggle to distinguish marketing claims from science. This review provides a comprehensive scientific framework for understanding which cosmetic peptides actually have evidence behind them, how they work, and what delivery challenges must be overcome for them to be effective in topical formulations. It bridges the gap between pharmaceutical peptide science and the beauty industry.","specificNumbers":"80+ peptide drugs on the market globally · Peptide categories: signal, carrier, neurotransmitter-inhibiting, enzyme-inhibiting · Multiple delivery systems reviewed","methodology":"Comprehensive narrative review published in the Journal of Peptide Science covering peptide sources, classifications, functional mechanisms in skin health, cosmetic applications, and delivery technologies.","limitations":"As a review, this synthesizes existing literature. Many cosmetic peptide claims lack rigorous clinical trial evidence. The review covers a broad range of peptides without deep analysis of specific formulations. Cosmetic studies often have small sample sizes and industry sponsorship. Delivery of peptides through intact skin remains a significant challenge that limits the efficacy of many products."},{"rthcId":"RPEP-14015","title":"Dual-Strategy Pullulan-Soluble Microneedles Based on LL37@ZIF-8 and Artificial Nanozyme Antioxidation for Infected Wound Healing.","authors":"Wang, Lijie; Wang, Zixuan; Chang, Jiarong; Zhou, Zhiyue; Wang, Xihan; Li, Zhaoming; Li, Dawei; Wang, Fang; Zhang, Wen; Gunarathne, Kannapathirage Dilini Maheshika; Meng, Xin","year":2025,"journal":"ACS applied materials & interfaces, 17(26), 37679-37697","doi":"10.1021/acsami.5c07412","pmid":"40524420","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14016","title":"Glucagon-like peptide-1 receptor agonists and pancreatic cancer risk: target trial emulation using real-world data.","authors":"Wang, Lindsey; Wang, QuanQiu; Li, Li; Kaelber, David C; Xu, Rong","year":2025,"journal":"Journal of the National Cancer Institute, 117(3), 476-485","doi":"10.1093/jnci/djae260","pmid":"39418202","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14017","title":"Semaglutide or Tirzepatide and Optic Nerve and Visual Pathway Disorders in Type 2 Diabetes.","authors":"Wang, Lindsey; Volkow, Nora D; Kaelber, David C; Xu, Rong","year":2025,"journal":"JAMA network open, 8(8), e2526327","doi":"10.1001/jamanetworkopen.2025.26327","pmid":"40788646","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14018","title":"Probiotics and Their Antimicrobial Metabolites: A Collegial Strategy for Food Bio-Preservation - A Review.","authors":"Wang, Lingling; Ren, Shuanshan; Behan, Atique Ahmed; Arain, Muhammad Asif; Ujjan, Nissar Ahmed; Zeng, Dequan; Li, Yufeng; Ma, Xingming","year":2025,"journal":"Food science & nutrition, 13(12), e71318","doi":"10.1002/fsn3.71318","pmid":"41356233","tags":["antimicrobial-peptides","probiotics","food-science"],"studyType":"Review","evidenceStrength":"Preliminary","keyFinding":"Probiotics produce antimicrobial peptides (AMPs) — including bacteriocins, enzymes, and peptide-based inhibitors — that kill foodborne pathogens and spoilage organisms. When probiotics and their AMPs are used together, they create a synergistic effect: the probiotics colonize food and form protective biofilms while simultaneously producing AMPs that disrupt bacterial membranes, inhibit cell wall synthesis, and suppress virulence genes.\n\nThis combination approach extends the shelf life of dairy, meat, and vegetable products by controlling microbial contamination. Many probiotic-derived AMPs are stable at high temperatures and varying pH levels, making them practical for food processing. The review positions probiotic-AMP combinations as natural, label-friendly alternatives to chemical food preservatives.","whyItMatters":"Consumer demand for natural food preservation is growing, and the food industry needs alternatives to chemical additives. Probiotic-derived antimicrobial peptides offer a dual benefit: they preserve food while being perceived as natural and health-promoting. As antibiotic resistance increases concern about chemical preservatives, biologically-derived AMPs represent a sustainable approach to food safety that aligns with both regulatory trends and consumer preferences.","specificNumbers":"Not applicable (narrative review covering multiple probiotic strains, AMPs, and food matrices)","methodology":"Comprehensive narrative review examining probiotic-derived antimicrobial peptides, their mechanisms of action against foodborne organisms, efficacy studies in various food products (dairy, meat, vegetables), and challenges to industrial-scale application.","limitations":"The review covers a broad field where most evidence comes from laboratory studies, with limited large-scale industrial application data. Strain specificity means results from one probiotic may not apply to others. Regulatory approval pathways for probiotic-AMP combinations in food vary by country. Potential sensory impacts (taste, texture) on food products are acknowledged but not thoroughly addressed. The synergistic effects claimed may not apply uniformly across all food types and storage conditions."},{"rthcId":"RPEP-14019","title":"The association of serum hsa-miR-21-5p expression with the severity and prognosis of heart failure with reduced ejection fraction.","authors":"Wang, Lingmiao; Guo, Ailin; Liang, Shuang; Yu, Lingling; Shen, Bai; Huang, Zhihang","year":2025,"journal":"BMC cardiovascular disorders, 25(1), 114","doi":"10.1186/s12872-024-04465-y","pmid":"39972425","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14020","title":"Semaglutide Reprograms Macrophages via the GLP-1R/PPARG/ACSL1 Pathway to Suppress Papillary Thyroid Carcinoma Growth.","authors":"Wang, Longlong; Zhang, Lele; Ma, Runsheng; Zhang, Yifei; Chang, Qungang; Yin, Detao","year":2025,"journal":"The Journal of clinical endocrinology and metabolism, 110(10), 2777-2789","doi":"10.1210/clinem/dgaf053","pmid":"39908200","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14021","title":"Economic evaluation of liraglutide vs dulaglutide or oral semaglutide in patients with type 2 diabetes mellitus: a systematic review.","authors":"Wang, Lu; Wang, Fei; Wang, Yinglin; Zhao, Quan","year":2025,"journal":"Diabetology & metabolic syndrome, 17(1), 358","doi":"10.1186/s13098-025-01927-x","pmid":"40859274","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14022","title":"Seaweeds-derived proteins and peptides: preparation, virtual screening, health-promoting effects, and industry applications.","authors":"Wang, Lu; Wang, Lang; Liu, Xiaoze; Lin, Xue; Fei, Tao; Zhang, Weimin","year":2025,"journal":"Critical reviews in food science and nutrition, 65(30), 6709-6736","doi":"10.1080/10408398.2025.2449596","pmid":"39812419","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14023","title":"Liraglutide modulates ALCAT1-Mediated cardiolipin remodeling to improve cardiac function in obese mice.","authors":"Wang, Lulu; Hu, Tingting; Zhang, Ruxuan; Shi, Yingzhou; Wang, Yan; Xuan, Qiuhui; Zhou, Xinli","year":2025,"journal":"Biochemical and biophysical research communications, 756, 151583","doi":"10.1016/j.bbrc.2025.151583","pmid":"40054063","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14024","title":"Effects of glucagon-like peptide-1 receptor agonists on patients with metabolic dysfunction-associated steatohepatitis: protocol for a systematic review and sequential meta-analysis.","authors":"Wang, Mei-Jun; Jiang, Yu-Nuo; Li, Pei-Pei; Wu, Yuan-Jie","year":2025,"journal":"Systematic reviews, 15(1), 14","doi":"10.1186/s13643-025-03011-x","pmid":"41373001","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14025","title":"Feasibility of the Implementation of Tools for Heart Failure Risk Prediction: A Randomized Controlled Pilot Trial.","authors":"Wang, Michael C; Dolan, Bridget; Huang, Xiaoning; Freaney, Priya M; Freed, Benjamin H; Vega, Lourdes; Markoski, Nikola; Wainright, Amy; Kane, Bonnie; Seegmiller, Laura E; Shah, Sanjiv J; Yancy, Clyde W; Neeland, Ian J; Ning, Hongyan; Lloyd-Jones, Donald M; Khan, Sadiya S","year":2025,"journal":"JACC. Advances, 4(8), 102004","doi":"10.1016/j.jacadv.2025.102004","pmid":"40664007","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14026","title":"Association between glucagon-like peptide-1 receptor agonists and ovarian cancer survival: A population-based cohort study.","authors":"Wang, Min; Dong, Tong; Lucero, Maria; Pan, Wanchun; Wang, Xin; Zhou, Ling; Meng, Yuanguang","year":2025,"journal":"Gynecologic oncology, 199, 57-63","doi":"10.1016/j.ygyno.2025.06.012","pmid":"40554181","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14027","title":"Depression and suicide/self-injury signals for weight loss medications: A disproportionality analysis of semaglutide, liraglutide, and tirzepatide in FAERS database.","authors":"Wang, Min; Yang, Zhiyun; Yan, Min; Liu, Shao; Xiao, Sa","year":2025,"journal":"Journal of affective disorders, 389, 119670","doi":"10.1016/j.jad.2025.119670","pmid":"40523410","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14028","title":"Exploring potential associations between GLP-1RAs and depressive disorders: a pharmacovigilance study based on FAERS and VigiBase data.","authors":"Wang, Min; Chen, Xiaohong; Liu, Zaiqiang; Li, Ziyi; Zhu, Zhihong; Liu, Shao; Xiao, Sa","year":2025,"journal":"EClinicalMedicine, 86, 103385","doi":"10.1016/j.eclinm.2025.103385","pmid":"40777864","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14029","title":"Improving viral-based gene delivery to mammalian cells through simple co-incubation with transportan peptide in vitro.","authors":"Wang, Nianwu; Hu, Xiangxiang; Pang, Hong-Bo","year":2025,"journal":"Journal of pharmaceutical sciences, 114(9), 103920","doi":"10.1016/j.xphs.2025.103920","pmid":"40721044","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Co-administration of Transportan (TP) with GFP-expressing AAVs and lentivirus enhanced transfection efficiency across multiple cell types with limited cytotoxicity. The approach worked in standard cell lines and, importantly, in difficult-to-transfect cells: the RAW264.7 macrophage cell line, bone marrow-derived macrophages (BMDMs), and retinal pigment epithelium (RPE) cells. The method requires only simple mixing — no specialized equipment, chemical modifications, or complex protocols.","whyItMatters":"Gene therapy is limited by how well viral vectors can get into target cells. Many clinically important cell types — immune cells for immunotherapy, retinal cells for eye diseases — are resistant to standard viral delivery. A simple, equipment-free method to boost delivery could accelerate gene therapy research and improve clinical outcomes. The ease of implementation (just mixing) makes it immediately adoptable by any lab.","specificNumbers":"","methodology":"Researchers used GFP-expressing AAV and lentiviral vectors as reporters. Transportan peptide was simply co-incubated with the viral vectors before adding to cells. Transfection efficiency was measured by GFP expression. Multiple cell lines were tested, including easy-to-transfect lines (for validation) and difficult-to-transfect cells: RAW264.7 macrophage line, primary bone marrow-derived macrophages, and primary retinal pigment epithelium cells. Cytotoxicity was assessed alongside transfection efficiency.","limitations":"All experiments were in vitro — in vivo gene delivery involves additional barriers (immune responses, tissue distribution) not captured here. The magnitude of transfection improvement was not quantified in the abstract. The mechanism by which Transportan enhances viral uptake (increased endocytosis? membrane interaction? receptor clustering?) was not fully elucidated. Long-term effects on cell health beyond acute cytotoxicity were not assessed. Whether the approach works with different AAV serotypes and at clinical-scale virus preparations is unknown."},{"rthcId":"RPEP-14030","title":"Glucagon-like peptide-1 receptor analog use is associated with reduced thromboembolic events compared with dipeptidyl peptidase-4 inhibitors in rheumatoid arthritis patients: A global retrospective cohort study.","authors":"Wang, Qi; Anthony, Donald D","year":2025,"journal":"Clinical rheumatology, 44(11), 4479-4485","doi":"10.1007/s10067-025-07709-0","pmid":"41015607","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14031","title":"Schistosoma japonicum peptide SJMHE1 promotes peripheral nerve regeneration via macrophage migrasome-derived miR-26b-5p targeting the PTEN/AKT axis.","authors":"Wang, Qian; Zhang, Wei; Zhao, Kai; Liu, Yue; Wang, Shang; Chen, Xingwen; Zhou, Dan; Wang, Juan; Feng, Yu; Li, Tao; Zhang, Wenchao; Dong, Liyang; Ma, Yongbin","year":2025,"journal":"Journal of translational medicine, 23(1), 1260","doi":"10.1186/s12967-025-07328-y","pmid":"41219730","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14032","title":"Targeting UBE2B-mediated U2AF1 degradation to alleviate endothelial dysfunction in renal ischemia-reperfusion injury: therapeutic potential of semaglutide.","authors":"Wang, Qian; Ren, Suxia; Jiao, Lijing; Zhu, Qiuxiao; Wang, Ting; Wang, Jing; Zhang, Lihui","year":2025,"journal":"Molecular biology reports, 53(1), 44","doi":"10.1007/s11033-025-11221-8","pmid":"41186784","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14033","title":"Exposure-Response Analysis of Efsubaglutide Alfa in Patients with Type 2 Diabetes Mellitus.","authors":"Wang, Qinghua; Jiang, Fan; Xu, Yulong; Lei, Yuyang; Zhang, Li; Sun, Xiaodong","year":2025,"journal":"Clinical pharmacokinetics, 64(12), 1785-1797","doi":"10.1007/s40262-025-01570-9","pmid":"41107649","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 465 drug-naïve T2DM patients (median age 51, mean baseline HbA1c 8.71%) receiving efsubaglutide alfa 1, 2, or 3 mg weekly:\n\n- Clear positive exposure-response relationship for all efficacy endpoints at weeks 24 and 52: HbA1c, fasting plasma glucose, meal tolerance glucose AUC, body weight, waist circumference, and BMI\n- A 10-fold increase in Cmin,ss corresponded to a 1.150% decrease in HbA1c at week 24\n- Baseline HbA1c, age, and neutralizing anti-drug antibodies influenced the exposure-response relationship\n- Treatment-related adverse events (nausea, diarrhea) correlated positively with drug exposure but showed tolerance development over time\n- The extended half-life from the Fc fusion design supports once-weekly or potentially biweekly dosing","whyItMatters":"The GLP-1 drug market is intensely competitive, with semaglutide and tirzepatide dominating. Efsubaglutide alfa represents a novel engineering approach — fusing two GLP-1 molecules to an antibody Fc fragment for extended duration. The clear dose-response relationship and potential for biweekly dosing could offer convenience advantages. Understanding which baseline characteristics (higher HbA1c, younger age, absence of anti-drug antibodies) predict better response helps personalize treatment decisions.","specificNumbers":"","methodology":"This was an exposure-response analysis using data from a Phase IIb/III randomized, double-blind, placebo-controlled trial (NCT04994288). Four hundred sixty-five drug-naïve T2DM participants received once-weekly subcutaneous efsubaglutide alfa (1, 2, or 3 mg) or placebo for 24 weeks (double-blind), followed by 28 weeks open-label. Steady-state pharmacokinetic parameters (Cmax,ss, Cmin,ss, Cavg,ss) were calculated. Regression analysis assessed exposure-response relationships for efficacy (glycemic, weight) and safety (adverse events) endpoints. Covariate analysis evaluated the influence of baseline characteristics on the exposure-response relationship.","limitations":"The study population was drug-naïve (no prior diabetes medication), which may limit generalizability to patients already on other therapies. The phase IIb/III trial design means final efficacy and safety conclusions await the full Phase III program. Anti-drug antibody development (neutralizing antibodies) was noted as an influencing factor, raising concerns about long-term immunogenicity. Direct comparison with other GLP-1 drugs was not performed. The exposure-response analysis is a secondary pharmacokinetic analysis, not the primary trial outcome."},{"rthcId":"RPEP-14034","title":"Exposure-Response Analysis of Efsubaglutide Alfa in Patients with Type 2 Diabetes Treated with Metformin.","authors":"Wang, Qinghua; Jiang, Fan; Xu, Yulong; Lei, Yuyang; Zhang, Li; Sun, Xiaodong","year":2025,"journal":"Clinical pharmacokinetics, 64(12), 1799-1809","doi":"10.1007/s40262-025-01569-2","pmid":"40991141","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 406 patients with type 2 diabetes on stable metformin, efsubaglutide alfa showed a robust inverse correlation between drug exposure and HbA1c, fasting plasma glucose, body weight, and BMI. Doubling steady-state trough concentrations reduced HbA1c by 0.211%, and every 100 ng/mL increase in average steady-state concentration led to a 0.5 kg reduction in body weight at week 24.\n\nThe drug also positively correlated with C-peptide levels during a meal tolerance test, indicating improved pancreatic beta-cell function. Gastrointestinal adverse events increased with higher exposure but decreased over time, suggesting tolerance development. Baseline HbA1c was identified as a predictor of treatment response.","whyItMatters":"The GLP-1 receptor agonist class has become central to diabetes and obesity treatment. Efsubaglutide alfa is a novel entrant using a unique design — two GLP-1 molecules fused to an IgG2 Fc fragment — enabling once-weekly dosing. Understanding its dose-response relationship helps optimize dosing and informs how it compares to established GLP-1 drugs.","specificNumbers":"","methodology":"Data came from a randomized, double-blind, placebo-controlled clinical trial (NCT04998032) with 406 type 2 diabetes patients on stable metformin. Participants received weekly subcutaneous injections of 1 mg or 3 mg efsubaglutide alfa, or placebo, over a 24-week double-blind period followed by a 28-week open-label period. Exposure-response modeling was used to quantify the relationship between drug levels and clinical outcomes.","limitations":"The study population was predominantly from a single clinical trial, which may limit generalizability. The exposure-response modeling approach, while informative, does not substitute for head-to-head comparison with other GLP-1 RAs. Long-term outcomes beyond 52 weeks were not assessed. The study does not report absolute HbA1c reductions from baseline for each dose group."},{"rthcId":"RPEP-14035","title":"circRNA hsa_circ_0072107 aggravates myocardial hypertrophy via its function as a competitive endogenous RNA of miR‑516b‑5p.","authors":"Wang, Rui; He, Yongli; Ma, Wuxia; Xu, Jindong; Zhong, Qi; Huang, Cheng","year":2025,"journal":"Molecular medicine reports, 32(3)","doi":"10.3892/mmr.2025.13597","pmid":"40539438","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14036","title":"Molecular recognition of two approved drugs Macimorelin and Anamorelin by the growth hormone secretagogue receptor.","authors":"Wang, Ruo-Lan; Sun, Jun; Liu, Heng; Guo, Shi-Meng; Zhang, Yu; Hu, Wen; Wang, Jiang; Liu, Hong; Zhuang, You-Wen; Jiang, Yi; Xie, Xin; Xu, H Eric; Wang, Yue","year":2025,"journal":"Acta pharmacologica Sinica, 46(11), 2998-3008","doi":"10.1038/s41401-025-01606-7","pmid":"40542284","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14037","title":"The role of gut microbiota in Tirzepatide-mediated alleviation of high-fat diet-induced obesity.","authors":"Wang, Ruonan; Lin, Zijing; He, Mingjie; Liao, Yi; Xu, Yunfei; Chen, Chengzhi; Duan, Xinhao; Jiang, XueJun; Qiu, Jingfu","year":2025,"journal":"European journal of pharmacology, 1002, 177827","doi":"10.1016/j.ejphar.2025.177827","pmid":"40516844","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14038","title":"Research progress in precision medicine for type 2 diabetes based on the GLP-1.","authors":"Wang, Sangui; Yuan, Chenrong; Wang, Haifeng; Ye, Xiyin; Ruan, Shun; Yi, Li; Yang, Wanyong; Wang, Zhi; Wang, Ni; Li, Jiahao; Feng, Xiaohui; Li, Yun; Tian, Yu; Wang, Quanlei","year":2025,"journal":"Frontiers in endocrinology, 16, 1721842","doi":"10.3389/fendo.2025.1721842","pmid":"41561058","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14039","title":"Biomimetic peptides in bone tissue engineering: From function to application.","authors":"Wang, Shan; Liu, Yihao; Zhou, Yue; Zheng, Weiwei; Mao, Yingji","year":2025,"journal":"Colloids and surfaces. B, Biointerfaces, 256(Pt 1), 115017","doi":"10.1016/j.colsurfb.2025.115017","pmid":"40795536","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14040","title":"Effect of α-Helix Neuropeptide on the Self-Assembly Behavior of β-Sheet Amyloid Short Peptides.","authors":"Wang, Shiwei; Wang, Pin; Li, Yanying; Duan, Xiaolin; He, Lulu; He, Zhen; Wu, Aiguo; Li, Juan","year":2025,"journal":"Nano letters, 25(33), 12593-12602","doi":"10.1021/acs.nanolett.5c02796","pmid":"40788309","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14041","title":"Nanoparticle platform preferentially targeting liver sinusoidal endothelial cells induces tolerance in CD4+ T cell-mediated disease models.","authors":"Wang, Shu-Hung; Serr, Isabelle; Digigow, Reinaldo; Metzler, Barbara; Surnov, Alexey; Gottwick, Cornelia; Alsamman, Muhammad; Krzikalla, Daria; Heine, Markus; Zahlten, Miriam; Widera, Agata; Mungalpara, Disha; Şeleci, Muharrem; Fanzutti, Marco; Marques Mesquita, Lígia Margarida; Vocaturo, Anna-Lisa; Herkel, Johannes; Carambia, Antonella; Schröter, Christian; Sarko, Dikran; Pohlner, Johannes; Daniel, Carolin; de Min, Cristina; Fleischer, Sabine","year":2025,"journal":"Frontiers in immunology, 16, 1542380","doi":"10.3389/fimmu.2025.1542380","pmid":"40165970","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14042","title":"Intestinal-related substances in obesity regulation: A comprehensive review.","authors":"Wang, Shuai-Yan; Zhang, Meng-Zhe; Chen, Zi-Ming; Li, Zi-Mu; Xie, Cong-Yi; Yang, Guan-Hu; Xu, Bin; Xu, Tian-Cheng","year":2025,"journal":"World journal of gastrointestinal pharmacology and therapeutics, 16(4), 111082","doi":"10.4292/wjgpt.v16.i4.111082","pmid":"41378072","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14043","title":"Strategic Design of Triple GLP-1R/GCGR/GIPR Agonists with Varied Receptor Potency: Achieving Comparable Glycemic and Weight Reduction Effects.","authors":"Wang, Shuang; Liu, Yun; Yan, Zhiming; Huang, Xianxian; Liao, Yonghe; Tang, Chunli; Jing, Lin; Zhou, Zhongbo; Han, Jing; Tang, Weizhong; Jiang, Neng","year":2025,"journal":"Journal of medicinal chemistry, 68(19), 20765-20788","doi":"10.1021/acs.jmedchem.5c02032","pmid":"40958513","tags":[],"studyType":"preclinical","evidenceStrength":"preliminary","keyFinding":"Researchers designed a novel triple-receptor agonist peptide (xGLP/GCG/GIP-32) that activates GLP-1R and GCGR potently but GIPR only weakly. Despite this intentionally unbalanced activation profile, the compound achieved weight loss effects superior to tirzepatide (a dual GLP-1R/GIPR agonist) and metabolic efficacy comparable to retatrutide (a triple agonist), both of which are leading obesity/diabetes drugs.\n\nThe study revealed that xGLP/GCG/GIP-32 exhibits biased agonism toward GIPR and GCGR, suggesting that maximal potency at all three receptors may not be necessary — and that strategically tuning the ratio of receptor activation could be a more effective design approach for next-generation metabolic peptide drugs.","whyItMatters":"The obesity drug pipeline is intensely focused on multi-receptor agonists following the success of semaglutide and tirzepatide. This study challenges the assumption that stronger activation at every target receptor leads to better outcomes, opening the door to more nuanced peptide drug design. If biased agonism at specific receptors proves advantageous, it could lead to drugs with better efficacy-to-side-effect profiles.","specificNumbers":"","methodology":"The researchers used sequence analysis, molecular dynamics simulations, molecular docking, and amino acid optimization to rationally design triple agonist peptides based on the GLP-1 scaffold. Lead compounds were tested for receptor activation profiles at GLP-1R, GCGR, and GIPR, then evaluated for metabolic effects including weight loss and glycemic control in animal models, with comparisons to tirzepatide and retatrutide.","limitations":"This is a preclinical study — the compounds have only been tested in animal models (mice), not in human clinical trials. The comparison to tirzepatide and retatrutide was based on preclinical metrics, which may not predict relative efficacy in humans. Long-term safety and tolerability data are not available."},{"rthcId":"RPEP-14044","title":"Protective Effect of Semaglutide on Obesity-Induced Renal Disease and Obesity-Induced Kidney Renal Clear Cell Carcinoma.","authors":"Wang, Shuqi; Zhang, Mengmeng; Yang, Xiaoman; Chen, Shuchun","year":2025,"journal":"Diabetes, metabolic syndrome and obesity : targets and therapy, 18, 805-818","doi":"10.2147/DMSO.S498447","pmid":"40124099","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14045","title":"Semaglutide and adenosine alleviate obesity-induced kidney injury, with observed modulation of the Txnip/NLRP3 pathway.","authors":"Wang, Shuqi; Pan, Xiaoyu; Liang, Ruiqing; Chen, Shuchun","year":2025,"journal":"Diabetology & metabolic syndrome, 17(1), 164","doi":"10.1186/s13098-025-01736-2","pmid":"40410781","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 48 mice divided into four groups (normal diet, high-fat diet, HFD + semaglutide, HFD + adenosine):\n\n- Semaglutide reduced weight in obese mice\n- Improved glucose and lipid metabolism markers\n- Reduced inflammation and oxidative stress\n- Improved glomerular and tubular kidney lesions (confirmed by light and electron microscopy)\n- Proteomics (LC-MS/MS) identified the Txnip/NLRP3 signaling pathway as involved in obesity-related kidney damage\n- Western blot confirmed that Txn, Txnip, and NLRP3 protein expression was elevated in obese mice and significantly reduced by semaglutide treatment\n- Adenosine showed similar protective effects","whyItMatters":"Obesity-related kidney disease is a growing global problem as obesity rates increase. Understanding how semaglutide protects the kidneys — beyond just causing weight loss — is important for expanding its therapeutic applications. The identification of the Txnip/NLRP3 inflammasome pathway provides a specific molecular mechanism that could be targeted by future therapies.","specificNumbers":"","methodology":"Forty-eight mice were divided into four groups: normal-fat diet, high-fat diet (HFD), HFD + semaglutide, and HFD + adenosine. After treatment, serum, urine, and kidney tissue were collected. Assessments included glucose/lipid metabolism markers, inflammatory and oxidative stress markers, kidney damage proteins, and urinary protein/creatinine ratios. Kidney pathology was examined by light and electron microscopy. Total kidney protein differences were analyzed by LC-MS/MS proteomics, with key findings validated by Western blot.","limitations":"This was an animal study in mice, and results may not directly translate to humans. The high-fat diet model produces a specific type of obesity that may differ from human obesity patterns. The study could not determine whether kidney protection was a direct effect of semaglutide on the kidneys or an indirect result of weight loss and metabolic improvement. The comparison with adenosine, while interesting, complicates interpretation of semaglutide-specific effects."},{"rthcId":"RPEP-14046","title":"The cost-utility and budget impact analyses of Tirzepatide versus once-weekly Semaglutide as add-on therapy to metformin in patients with type 2 diabetes mellitus in China.","authors":"Wang, Sihua; Fan, Duncong; Yao, Qinhong; Sun, Xiaojie","year":2025,"journal":"Diabetes, obesity & metabolism, 27(9), 5269-5279","doi":"10.1111/dom.16580","pmid":"40600464","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tirzepatide 5 mg and 10 mg produced incremental QALYs of 0.05 and 0.09 compared to semaglutide 1 mg. However, the incremental cost-utility ratios were $445,125/QALY and $543,829/QALY respectively — both far exceeding China's willingness-to-pay threshold of $29,600/QALY. Adding tirzepatide to the national health insurance would cost an additional $80-490 million over 5 years, but overall healthcare expenditures could decrease due to reduced out-of-pocket costs for patients.","whyItMatters":"As GLP-1-based therapies become the standard of care for type 2 diabetes globally, understanding their cost-effectiveness in different healthcare systems is critical for drug formulary decisions. This study shows that even when a newer peptide drug offers clinical advantages, the price premium may not justify the incremental benefit — an important consideration for the world's largest diabetes population.","specificNumbers":"","methodology":"Cost-utility analysis using clinical efficacy data from the SURPASS-2 trial and the UK Prospective Diabetes Study Outcomes Model Version 2.2. The analysis took the perspective of Chinese healthcare providers, incorporating direct medical costs and quality-adjusted life years over a long-term simulation horizon. Sensitivity analyses tested the robustness of findings. A separate budget impact analysis estimated 5-year financial consequences for China's national health insurance system.","limitations":"The model relies on clinical data from the SURPASS-2 trial, which may not perfectly represent real-world Chinese patient populations. The UKPDS Outcomes Model was developed from Western populations and may not fully capture disease progression patterns in Chinese patients. Drug prices in China are subject to negotiation and may change significantly. The analysis uses a healthcare provider perspective and may undervalue broader societal benefits. Long-term simulation introduces compounding uncertainty."},{"rthcId":"RPEP-14047","title":"Recent advances in mineralocorticoid receptor antagonists for heart failure with preserved ejection fraction: focus on finerenone in the era of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists.","authors":"Wang, Tian-Yu; Zhang, Lei; Wang, Huan-Yi; Jiang, Fen-Fen","year":2025,"journal":"Frontiers in pharmacology, 16, 1725782","doi":"10.3389/fphar.2025.1725782","pmid":"41476792","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14048","title":"Molecular insights into the formation of polymeric nanoassemblies of the anticancer peptide PEN-FFW.","authors":"Wang, Tianqi; Lazareva, Polina A; Malinovskaya, Julia; Panczyk, Tomasz; Wen Hui, Joyce Ang; Dhakal, Namrata; Liu, Beijia; Qin, Qiuhua; Kovshova, Tatyana; Sur, Somok; Vadekhina, Veronika; Ivanova, Anna V; Valikhov, Marat; Reich, Gabriele; Chen, Wenqian; Gelperina, Svetlana; Abakumov, Maxim A; Wacker, Matthias G","year":2025,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 388(Pt 2), 114364","doi":"10.1016/j.jconrel.2025.114364","pmid":"41167337","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Researchers developed a stable nanoformulation for the anticancer peptide PEN-FFW by encapsulating it in carboxymethyl cellulose-PLGA nanoparticles stabilized with polysorbate 80. Optimization using a Box-Behnken design achieved a 50% increase in encapsulation efficiency and enhanced storage stability. The formulation showed superior cellular uptake and cytotoxicity in liver cancer cells in vitro, and significantly greater hepatic retention compared to free peptide in mice.","whyItMatters":"A major challenge for peptide cancer drugs is that they break down quickly and don't reach tumors effectively. PEN-FFW shows promise against hepatocellular carcinoma (liver cancer), but its sensitivity to shear and poor stability have blocked development. This nanoformulation solves both problems, demonstrating that smart delivery systems can unlock the therapeutic potential of otherwise unstable peptide drugs.","specificNumbers":"50% increase in encapsulation efficiency · enhanced storage stability · superior cellular uptake in vitro · greater hepatic retention in vivo · CMC-PLGA core · polysorbate 80 stabilizer · Box-Behnken 4-factor optimization","methodology":"PEN-FFW was encapsulated in carboxymethyl cellulose-PLGA nanoparticles stabilized by polysorbate 80. Drug-excipient interactions were characterized by QCM-D, FTIR, and DLS. Molecular modeling predicted peptide binding within the polymer core. A four-factor, three-level Box-Behnken design optimized formulation parameters. In vitro testing assessed cellular uptake and cytotoxicity in HepG2 cells. In vivo studies in mice measured hepatic retention.","limitations":"Anti-tumor efficacy in tumor-bearing animal models was not reported — only hepatic retention was measured in vivo. Long-term stability under various storage conditions was not fully characterized. The scalability of the optimized formulation for commercial manufacturing was not assessed. Toxicity of the nanoformulation versus free peptide in healthy tissue was not compared."},{"rthcId":"RPEP-14049","title":"Developing a novel algorithm to identify incident and prevalent dementia in Medicare claims-the ARIC Study.","authors":"Wang, Tiansheng; Pate, Virginia; Kim, Dae Hyun; Power, Melinda C; Garden, Gwenn; Palta, Priya; Knopman, David; Jonsson-Funk, Michelle; Stürmer, Til; Kucharska-Newton, Anna M","year":2025,"journal":"American journal of epidemiology, 194(12), 3537-3548","doi":"10.1093/aje/kwaf166","pmid":"40754790","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14050","title":"Comparative Efficacy and Safety of Oral Semaglutide in Asians and Non-Asians Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.","authors":"Wang, Tianzuo; Cui, Yuying; Liao, Lin","year":2025,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 16(3), 449-470","doi":"10.1007/s13300-024-01689-1","pmid":"39797937","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14051","title":"Bioactive Polysaccharides from Fermented Dendrobium officinale: Structural Insights and Their Role in Skin Barrier Repair.","authors":"Wang, Wanshuai; Zou, Anqi; Yu, Qingtao; Wang, Zhe; Tan, Daotong; Yang, Kaiye; Cai, Chao; Yu, Guangli","year":2025,"journal":"Molecules (Basel, Switzerland), 30(13)","doi":"10.3390/molecules30132875","pmid":"40649389","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14052","title":"Semaglutide Mitigates Ischemic Brain Injury by Inhibiting Ferroptosis via Modulation of FoXO1 and DRP1 Pathways.","authors":"Wang, Weihua; Pang, Meng; Zhang, Yifeng; Hou, Shuai; Xia, Yulei; Shi, Youkui; Zhang, Xiaojun; Wang, Yanqiang","year":2025,"journal":"Molecular neurobiology, 62(12), 16168-16188","doi":"10.1007/s12035-025-05253-1","pmid":"40748430","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Using a rat model of ischemic stroke (middle cerebral artery occlusion/reperfusion), semaglutide reduced brain tissue damage and neuronal death. At the molecular level, semaglutide activated GLP-1 receptors to modulate two key pathways:\n\n1. **FoXO1/GPX4 pathway**: Semaglutide regulated the FoXO1 transcription factor and increased GPX4 (a key anti-ferroptosis enzyme), inhibiting autophagy (via reduced Beclin1) and preventing ferroptotic cell death.\n\n2. **DRP1/ACSL4 pathway**: Semaglutide suppressed DRP1-mediated mitochondrial fission (fragmentation), promoted Mfn2-mediated mitochondrial fusion, increased ATP production, and reduced reactive oxygen species (ROS). This improved mitochondrial health and reduced ACSL4-dependent ferroptosis.\n\nBioinformatics analysis predicted these mechanisms, which were then validated through Western blotting, RT-PCR, immunofluorescence, and ELISA experiments.","whyItMatters":"Stroke is a leading cause of death and disability worldwide, and treatment options during the critical reperfusion period are extremely limited. If semaglutide — a drug already approved and widely used for diabetes and obesity — also protects the brain during stroke, it could be repurposed for neuroprotection. Understanding the specific mechanism (ferroptosis inhibition via mitochondrial protection) also opens new targets for stroke drug development.","specificNumbers":"","methodology":"Researchers first used bioinformatics analysis to predict how semaglutide might protect against cerebral ischemia-reperfusion injury. They then validated these predictions using a rat middle cerebral artery occlusion/reperfusion (MCAO/R) model — a standard experimental stroke model. Brain tissue from the ischemic penumbra (the salvageable area around the stroke core) was analyzed using histopathology, Western blotting, RT-PCR, immunofluorescence, and ELISA to measure markers of cell death, autophagy, mitochondrial dynamics, and ferroptosis.","limitations":"This is an animal study using an artificially induced stroke model in rats, which may not fully replicate human stroke pathophysiology. The specific semaglutide dose, timing of administration (before, during, or after stroke), and treatment duration were not detailed in the abstract. Bioinformatics predictions, while validated experimentally, rely on existing database annotations that may be incomplete. No behavioral or functional recovery outcomes were reported — only molecular and histological markers."},{"rthcId":"RPEP-14053","title":"Inetetamab triggers cardiotoxicity through its interaction with apoptosis, oxidative stress and autophagy pathways.","authors":"Wang, Weiqun; Zhang, Hongliang; Qu, Yikun; Li, Yue; Peng, Peng; Lu, Chengbo; Zhao, Xinyue; Cai, Ziteng; Peng, Chaonan; Guo, Xiaoli; Guo, Yuxin; Li, Jie; Li, Xuebin; Jia, Linlin; Yang, Guangyuan","year":2025,"journal":"Scientific reports, 15(1), 20987","doi":"10.1038/s41598-025-02125-5","pmid":"40593780","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14054","title":"Associations of semaglutide with Alzheimer's disease-related dementias in patients with type 2 diabetes: A real-world target trial emulation study.","authors":"Wang, William; Davis, Pamela B; Qi, Xin; Gurney, Mark; Perry, George; Volkow, Nora D; Kaelber, David C; Xu, Rong","year":2025,"journal":"Journal of Alzheimer's disease : JAD, 106(4), 1509-1522","doi":"10.1177/13872877251351329","pmid":"40552638","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14055","title":"Effects of Baduanjin on exercise tolerance, cardiac function, and quality of life in patients with heart failure: A systematic review and meta-analysis.","authors":"Wang, Wujiao; Qi, Jia; Wan, Jie; Lin, Zhao; Yang, Peng; Ge, Hongyue; Chang, Peifen; Li, Tianli","year":2025,"journal":"Complementary therapies in medicine, 95, 103280","doi":"10.1016/j.ctim.2025.103280","pmid":"41176179","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14056","title":"The Efficacy of Semaglutide on Hypothalamic Obesity Caused by Craniopharyngioma Surgery.","authors":"Wang, Xi; Ma, Hailu; Wang, Fang; Long, Hongmei; Li, Chenyang; Nie, Min; Han, Qin; Mao, Jiangfeng; Wu, Xueyan","year":2025,"journal":"Clinical endocrinology, 103(3), 359-365","doi":"10.1111/cen.15262","pmid":"40432243","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In the semaglutide group (n=14), weight decreased significantly from 108.9 ± 20.9 kg to 100.8 ± 20.2 kg at 3 months (p < 0.001) and to 96.1 ± 23.1 kg at 6 months (p < 0.001) — a total loss of ~12.8 kg. At 3 months, 64.3% achieved >5% weight loss; at 6 months, this rose to 90%. The control group (n=9) on lifestyle intervention alone experienced weight gain over the same period.\n\nThis is particularly notable because hypothalamic obesity is driven by brain damage rather than behavioral factors, and most weight loss interventions are ineffective in this population.","whyItMatters":"Hypothalamic obesity after brain tumor surgery is one of the most treatment-resistant forms of obesity — patients have a damaged appetite control center and most weight management strategies fail. This study provides the first evidence that semaglutide can produce meaningful weight loss in this population, offering hope for patients who previously had almost no effective treatment options.","specificNumbers":"","methodology":"Prospective clinical study at Peking Union Medical College Hospital (March 2023 to October 2024). 23 obese patients post-craniopharyngioma surgery were divided into semaglutide treatment (n=14) and lifestyle intervention control (n=9). Weight, BMI, waist circumference, blood glucose, and lipid profiles were measured at baseline, 3 months, and 6 months. Registered trial (ChiCTR2400094933).","limitations":"Small sample size (n=23 total, 14 treated). Non-randomized assignment to groups may introduce selection bias. The control group was smaller (n=9) and may not be fully comparable. Only 6 months of follow-up — long-term weight maintenance after hypothalamic damage is unknown. No blinding of patients or investigators. The study was conducted at a single center in China."},{"rthcId":"RPEP-14057","title":"Cholesterol modified defense peptide as an EMP2-siRNA delivery system for synergistic immunogene therapy against breast cancer.","authors":"Wang, Xiaoyun; Chen, Siliang; He, Gu; Zhu, Yanghui; Zhang, Nan; Gong, Changyang; Li, Xiang; Chen, Yujuan","year":2025,"journal":"Materials today. Bio, 35, 102321","doi":"10.1016/j.mtbio.2025.102321","pmid":"41080733","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The engineered HH2-siEMP2 nanoparticles achieved effective EMP2 gene silencing in breast cancer cells, leading to significant suppression of tumor migration and invasion both in vitro and in vivo.\n\nBeyond direct anti-tumor effects, the HH2-cholesterol conjugate demonstrated immunomodulatory properties: promoting Th1 cell expansion (pro-inflammatory, anti-tumor), reducing Th2 cells (which can promote tumor tolerance), decreasing immunosuppressive regulatory T cells (Tregs), and restoring the Th17/Treg balance. The nanoparticles showed optimal size, positive surface charge, excellent serum stability, and enhanced cellular uptake.","whyItMatters":"Getting gene therapy into cancer cells effectively remains one of the biggest challenges in oncology. This study solves two problems at once: the defense peptide not only delivers the therapeutic cargo efficiently but also activates anti-cancer immunity — turning the delivery vehicle itself into part of the treatment. This dual-function approach could make gene-based cancer therapies more potent and practical.","specificNumbers":"","methodology":"Defense peptide HH2 was conjugated with cholesterol to form self-assembling nanoparticles that encapsulate EMP2-targeting siRNA. The nanoparticles were characterized for size, surface charge, and serum stability. Cellular uptake and EMP2 silencing efficacy were assessed in breast cancer cell lines. Anti-tumor effects (migration, invasion) were evaluated in vitro and in vivo in animal models. Immune cell profiling (Th1, Th2, Th17, Treg populations) assessed the immunomodulatory properties.","limitations":"This is a preclinical study using cell lines and animal models. Clinical translation would need to address peptide stability, potential immunogenicity, and scalable manufacturing of the nanoparticles. The specific breast cancer subtypes and clinical contexts where this approach would be most effective are not yet defined. Long-term safety and pharmacokinetics were not characterized."},{"rthcId":"RPEP-14058","title":"Engineering an Escherichia coli Autolytic System for Overexpression of a Collagen-Mimetic Peptide with Enhanced Hemostatic Activity.","authors":"Wang, Xinglong; Chen, Qiming; Huang, Zhongshi; Han, Jiayao; Xu, Chen; Zhou, Jingwen; Zhang, Lixing; Ma, Fuqiang","year":2025,"journal":"ACS synthetic biology, 14(5), 1701-1709","doi":"10.1021/acssynbio.5c00056","pmid":"40314450","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14059","title":"Association of Novel Mutations in the Vasoactive Intestinal Peptide Receptor-1 Gene with Egg Shell Thickness in Three Strains of Laying-Type Quail.","authors":"Wang, Xinle; Chen, Huricha; Lei, Ying; Wang, Qiankun; Li, Gan; Bai, Junyan","year":2025,"journal":"Animals : an open access journal from MDPI, 15(10)","doi":"10.3390/ani15101373","pmid":"40427251","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14060","title":"GATA3 and IFNG as Potential Molecular Biomarkers for Differentiating Heart Failure with Preserved Ejection Fraction with Normal Versus Elevated BNP Levels.","authors":"Wang, Xinyi; Jia, Kegang; Wang, Mengwei; Zhang, Yunqiang; Ye, Yingnan; Hou, Ze","year":2025,"journal":"International heart journal, 66(6), 947-955","doi":"10.1536/ihj.25-159","pmid":"41320334","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14061","title":"GLP-1 receptor agonists synergistic effects of metabolic reprogramming and cardioprotection.","authors":"Wang, Xuan; Qi, Mengmeng; Yang, Lili; Yang, Libo; Wang, Xiaoyue; Zhang, Fang; Cui, Yukun; Wang, Dongxin; Wang, Yangang; Lv, Wenshan","year":2025,"journal":"Frontiers in endocrinology, 16, 1614726","doi":"10.3389/fendo.2025.1614726","pmid":"41158620","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14062","title":"LL-37 and Its Truncated Fragments Modulate Amyloid-β Dynamics, Aggregation and Toxicity Through Hetero-Oligomer and Cluster Formation.","authors":"Wang, Xue; Österlund, Nicklas; Pereira Curia, Guadalupe; Mörman, Cecilia; Sternke-Hoffmann, Rebecca; L Ilag, Leopold; Gräslund, Astrid; Wang, Guangshun; Luo, Jinghui","year":2025,"journal":"Angewandte Chemie (International ed. in English), 64(43), e202516241","doi":"10.1002/anie.202516241","pmid":"40916348","tags":["antimicrobial-and-bioactive-peptides","neuroscience-and-neuropeptides"],"studyType":"in-vitro","evidenceStrength":"low","keyFinding":"LL-37 and three of its truncated fragments all formed hetero-oligomers and nanoclusters with amyloid-beta 40 (Aβ40), inhibiting the formation of amyloid fibrils — the toxic protein clumps associated with Alzheimer's disease. However, the full-length LL-37 and one specific fragment (LL-37₁₉₋₂₈) were the most potent inhibitors.\n\nThese two peptides formed more hetero-oligomers and smaller nanoclusters with Aβ40, which appear to represent an 'off-pathway' dead end that prevents productive aggregation. At the microscale, they also rapidly formed larger clusters with Aβ, and uniquely affected the elongation phase of fibril growth — a step the other fragments could not influence.","whyItMatters":"Amyloid-beta aggregation is a central feature of Alzheimer's disease, and finding molecules that can disrupt this process is a major research goal. LL-37 is your body's own antimicrobial peptide — discovering it can also interfere with Alzheimer's-related protein clumping opens an unexpected connection between innate immunity and neurodegeneration. Understanding exactly how LL-37 does this could guide the design of new anti-amyloid therapeutics.","specificNumbers":"4 peptides tested (LL-37, LL-37₉₋₃₂, LL-37₁₈₋₂₉, LL-37₁₉₋₂₈) · Aβ40 aggregation inhibited by all · LL-37 and LL-37₁₉₋₂₈ showed strongest inhibition · Affected primary nucleation, secondary nucleation, and elongation","methodology":"In vitro biophysical study using four LL-37 peptide variants and Aβ40. Researchers used nanoscale analysis techniques to observe hetero-oligomer and nanocluster formation, microscale analysis to track cluster assembly, and kinetic modeling to determine which stages of amyloid aggregation each peptide affected (primary nucleation, secondary nucleation, and elongation).","limitations":"Entirely in vitro — no cell culture toxicity assays or animal models were used. Only Aβ40 was tested, not the more aggregation-prone Aβ42. The behavior of LL-37 fragments in the complex brain environment could differ substantially from test-tube conditions. No therapeutic dosing or delivery was explored."},{"rthcId":"RPEP-14063","title":"Znhit1 alleviates nitroglycerin-induced hyperalgesia in migraine mice via the inhibition of NOD-like receptor signaling pathway.","authors":"Wang, Xue; Tang, Jianhua; Hou, Yiwei; Sui, Changbai","year":2025,"journal":"Molecular pain, 21, 17448069251389420","doi":"10.1177/17448069251389420","pmid":"41312586","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In a nitroglycerin-induced migraine mouse model:\n\n- Znhit1 expression was reduced in the trigeminal nucleus caudalis (TNC) — the brain's migraine pain center\n- Overexpression of Znhit1 produced multiple beneficial effects:\n  - Alleviated thermal and mechanical hyperalgesia (pain hypersensitivity)\n  - Upregulated 5-HT (serotonin) levels\n  - Inhibited c-Fos expression (a marker of neuronal activation)\n  - Reduced CGRP expression (the key migraine neuropeptide)\n  - Downregulated inflammatory markers: IL-6, IL-1β, TNF-α, COX-2, iNOS\n  - Inhibited NLRP3 inflammasome activation\n\nIn vitro: Znhit1 silencing in microglia enhanced inflammation and apoptosis via NLRP3 activation, which was reversed by the specific NLRP3 inhibitor MCC950 — confirming NLRP3 as the key downstream target.","whyItMatters":"CGRP-targeting drugs (anti-CGRP antibodies and gepant antagonists) have revolutionized migraine treatment but don't work for everyone. Understanding what naturally regulates CGRP expression could reveal new therapeutic targets. Znhit1 represents a novel upstream regulator of CGRP that operates through the NLRP3 inflammasome pathway. This connects migraine biology to the broader field of inflammasome-mediated diseases and could open new treatment avenues, including the potential use of existing NLRP3 inhibitors for migraine.","specificNumbers":"","methodology":"A chronic migraine mouse model was established by repeated intraperitoneal nitroglycerin injection. Znhit1 expression was measured by qPCR and western blot. Pain was assessed by Von Frey monofilaments (mechanical) and hot plate assay (thermal). Inflammatory markers were measured by ELISA and western blot. Molecular mechanisms were explored in vitro using BV2 microglial cells with Znhit1 overexpression or silencing, LPS stimulation, and the NLRP3 inhibitor MCC950.","limitations":"This is a preclinical mouse study — the nitroglycerin migraine model captures some aspects of human migraine but not all. Znhit1 overexpression was achieved by viral vector injection, which is not a practical therapeutic approach. The relationship between Znhit1 levels and human migraine has not been established. The specific cell types expressing Znhit1 in the TNC are not fully characterized. In vitro experiments used LPS-stimulated microglia, which may not perfectly model migraine-associated inflammation."},{"rthcId":"RPEP-14064","title":"Identification of serum C4BPA as a potential diagnostic marker of right ventricular remodelling via proteomic analysis.","authors":"Wang, Xuenan; Yu, Cheng; Li, Meiling; Cai, Huiling; Yang, Yongjian; Lan, Cong","year":2025,"journal":"ESC heart failure, 12(4), 2843-2854","doi":"10.1002/ehf2.15292","pmid":"40237358","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14065","title":"Efficacy of GLP-1-based Therapies on Metabolic Dysfunction-associated Steatotic Liver Disease and Metabolic Dysfunction-associated Steatohepatitis: A Systematic Review and Meta-analysis.","authors":"Wang, Yahao; Zhou, Yue; Wang, Zhihong; Ni, Yunzhi; Prud'homme, Gerald J; Wang, Qinghua","year":2025,"journal":"The Journal of clinical endocrinology and metabolism, 110(10), 2964-2979","doi":"10.1210/clinem/dgaf336","pmid":"40489581","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14066","title":"Unraveling the Osteogenic Activity and Molecular Mechanism of an Antioxidant Collagen Peptide in MC3T3-E1 Cells.","authors":"Wang, Yali; Wang, Yue; Zhuang, Xiaoyan; Zhang, Yonghui; Fang, Baishan; Fu, Yousi","year":2025,"journal":"Nutrients, 17(5)","doi":"10.3390/nu17050824","pmid":"40077694","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14067","title":"Challenges and opportunities on achieving an adequate delivery efficiency and immunogenicity with peptide-based anticancer vaccines.","authors":"Wang, Yanqing; Sun, Da; Laney, Victoria; Wang, Hong; Wang, Li Lily; Lu, Zheng-Rong","year":2025,"journal":"Advanced drug delivery reviews, 225, 115675","doi":"10.1016/j.addr.2025.115675","pmid":"40818568","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14068","title":"Dionysus or apollo, skeletal muscle mass changes in type 2 diabetes with sarcopenia receiving GLP-1 receptor agonist: systematic review and meta-analysis.","authors":"Wang, Yanying; Lan, Boya; Zhang, Shuo; Mu, Yue; Mi, Jia; Yu, Jing; Zhan, Qun; Luo, Baoling; Lin, Fuyang; Teng, Jia; Wang, Xiuge; Yan, Guanchi","year":2025,"journal":"Diabetology & metabolic syndrome, 17(1), 315","doi":"10.1186/s13098-025-01877-4","pmid":"40770817","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 9 randomized controlled trials with 1,089 participants, GLP-1 receptor agonists produced significant reductions in fat-related measures: body fat ratio decreased (MD = -2.76, p < 0.01), fat mass decreased (MD = -8.00, p < 0.01), and BMI decreased (MD = -1.83, p < 0.01).\n\nCritically, muscle-related measures were not significantly affected: lean body mass showed a non-significant increase (MD = +4.61, p = 0.31) and skeletal muscle index was also unchanged (MD = +0.59, p = 0.19). Body weight change overall was not statistically significant (MD = -2.25, p = 0.20), suggesting the weight composition shifted favorably from fat to a relatively preserved lean mass.","whyItMatters":"The fear of losing muscle mass on GLP-1 drugs has been a major concern for both clinicians and patients, particularly in populations already vulnerable to sarcopenia. This meta-analysis directly addresses that concern in the highest-risk group — older adults with type 2 diabetes who already have muscle wasting. The finding that fat is preferentially lost while muscle is preserved is clinically reassuring and could influence prescribing decisions for this population.","specificNumbers":"","methodology":"Systematic review and meta-analysis of randomized controlled trials, registered on PROSPERO (CRD42023473528). Nine databases including PubMed, Embase, Cochrane Library, Web of Science, and four Chinese databases were searched through July 2025. Grey literature sources were also included. Random effects models were used regardless of heterogeneity. Publication bias was assessed with funnel plots.","limitations":"Only 9 trials with 1,089 total participants were included, which is relatively small for a meta-analysis. The body weight reduction was not statistically significant (p = 0.20), which may indicate underpowering or heterogeneity across trials. Different GLP-1 receptor agonists were pooled regardless of structure, though subtype differences may exist. Methods of measuring body composition varied across studies. Trial durations were not specified in the abstract, making it unclear whether longer-term muscle effects might differ."},{"rthcId":"RPEP-14069","title":"Comparative effectiveness and safety of sodium-glucose cotransporter 2 inhibitors vs glucagon-like peptide 1 receptor agonists in elderly patients with type 2 diabetes mellitus: a meta-analysis.","authors":"Wang, Yao; Wu, Haoming; Yang, Jingxian; Ma, Jun; Li, Hongling; He, Xinyu; Xiao, Yibo; Pan, Yan","year":2025,"journal":"Frontiers in endocrinology, 16, 1486655","doi":"10.3389/fendo.2025.1486655","pmid":"40933374","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14070","title":"Dual Strategies Based on Golgi Apparatus/Endoplasmic Reticulum Targeting and Anchoring for High-Efficiency siRNA Delivery and Tumor RNAi Therapy.","authors":"Wang, Yashi; Yin, Sheng; He, Dan; Zhang, Yujia; Dong, Ziyan; Tian, Zhipeng; Li, Jiayu; Chen, Fang; Wang, Yang; Li, Man; He, Qin","year":2025,"journal":"ACS nano, 19(3), 3791-3806","doi":"10.1021/acsnano.4c14778","pmid":"39801087","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14071","title":"Regulation of nanoparticle exocytosis direction via receptors transfer: A novel strategy to enhance therapeutic efficacy of semaglutide.","authors":"Wang, Yating; Ni, Mingjie; Huang, Minyi; Xing, Liyun; Liu, Xi; Jia, Fuya; Huang, Yuan","year":2025,"journal":"International journal of pharmaceutics, 674, 125439","doi":"10.1016/j.ijpharm.2025.125439","pmid":"40064382","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14072","title":"Quantitative analysis of the efficacy characteristics and influencing factors of weight loss drugs in children and adolescents.","authors":"Wang, Yexuan; Chen, Junchao; He, Yingchun; Lv, Yinghua; Guo, Haoyang; Zheng, Qingshan; Li, Lujin","year":2025,"journal":"Diabetes, obesity & metabolism, 27(10), 5538-5553","doi":"10.1111/dom.16599","pmid":"40642833","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14073","title":"Effects of ligustrazine on energy metabolism in migraine rats based on mitochondria-inflammation pathway.","authors":"Wang, Yicheng; Wang, Yongli; Yue, Guangxin; Lin, Jingjing; Liu, Xueying; Wang, Liwei; Zhao, Yonglie","year":2025,"journal":"Neuroscience letters, 844, 138035","doi":"10.1016/j.neulet.2024.138035","pmid":"39505199","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14074","title":"Therapeutic Potential of Antimicrobial Peptide Scymicrosin7-26 against the Emerging Pathogen Acinetobacter ursingii Isolated from Litopenaeus vannamei.","authors":"Wang, Ying; Li, Hanxiao; Hao, Hua; Zhou, Ying; Chen, Fangyi; Wang, Ke-Jian","year":2025,"journal":"Probiotics and antimicrobial proteins","doi":"10.1007/s12602-025-10866-y","pmid":"41348170","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14075","title":"Neurochemical Alterations in Aggression: A Meta-Analysis.","authors":"Wang, Yong-Ming; Cao, Yong-Liang; Yang, Jia-Sheng; Sun, Qi-Hao; Fan, Bing-Bing; Wang, Ying; Tian, Fang; Xu, Xiao-Dan; Zhang, Meng","year":2025,"journal":"Psychiatry research, 351, 116595","doi":"10.1016/j.psychres.2025.116595","pmid":"40543113","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14076","title":"Interaction between Brain Natriuretic Peptide and QTc Prolongation on Mortality in Patients with Stroke-Heart Syndrome.","authors":"Wang, Yongle; He, Mingyi; Wang, Lanjing; Elmadhoun, Omar; Liu, Fangyan; Zhao, Wenbo; Ren, Changhong; Ding, Yuchuan; Ji, Xunming; Li, Sijie","year":2025,"journal":"Aging and disease","doi":"10.14336/AD.2025.10711","pmid":"40901986","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14077","title":"The Sustained Effects of Bioactive Collagen Peptides on Skin Health: A Randomized, Double-Blind, Placebo-Controlled Clinical Study.","authors":"Wang, Yu; Zhu, Weixing; Luo, Wenyu; Ma, Yanfeng; Zhou, Yue","year":2025,"journal":"Journal of cosmetic dermatology, 24(12), e70565","doi":"10.1111/jocd.70565","pmid":"41311286","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14078","title":"Unraveling the relationship between inflammation and cluster headache.","authors":"Wang, Yu-Wen; Yang, Xu-Hong; Zheng, Xin-Hui; Zhou, Gao-Shui; Zhao, Xiao-Xia; Zhao, Yi-Lan; Wu, Shu-Hong","year":2025,"journal":"Frontiers in neurology, 16, 1548522","doi":"10.3389/fneur.2025.1548522","pmid":"40248013","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14079","title":"Bioactive peptide HX-12C enhances fibroblast function through TGF-β/Smad signaling pathway and promotes wound healing in vitro and in vivo.","authors":"Wang, Yujing; Wang, Baisheng; Li, Yiyang; Cao, Zhenmin; Qin, Zuodong; Luo, Xiaofang; Li, Kun","year":2025,"journal":"Peptides, 193, 171446","doi":"10.1016/j.peptides.2025.171446","pmid":"41077071","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14080","title":"Incretin-Based Drugs and the Risk of Dementia Among Patients with Type 2 Diabetes.","authors":"Wang, Yun-Han; Johnson, Kyle; Beradid, Sarah; Yin, Hui; Yu, Oriana H Y; Suissa, Samy; Azoulay, Laurent; Renoux, Christel","year":2025,"journal":"Drug safety","doi":"10.1007/s40264-025-01623-9","pmid":"41123870","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14081","title":"Enhancing Transdermal Delivery: The Role of Gecko-Derived Cathelicidin Peptide G3CY-10 in UV-Induced Skin Photoaging.","authors":"Wang, Yunjiao; Ma, Zicheng; Li, Fengshuo; Li, Xuanzeng; Gao, Ningyang; Wang, Junhan; Cai, Shasha","year":2025,"journal":"Biomolecules, 15(11)","doi":"10.3390/biom15111515","pmid":"41301433","tags":["cathelicidins","skin-health"],"studyType":"preclinical","evidenceStrength":"preliminary","keyFinding":"A modified cathelicidin peptide derived from geckos — called G3CY-10 — delivered through a microemulsion gel system protected mouse skin against UV-induced photoaging. The gel formulation (lecithin-ethanol-butyl acetate, km = 1:1) showed notable stability and significantly enhanced transdermal delivery of the peptide.\n\nIn UV-exposed mice, the G3CY-10 gel reduced epidermal thickening, suppressed sebaceous gland overgrowth, and restored collagen fiber density. The peptide worked primarily by blocking UV-induced collagen breakdown and restoring levels of superoxide dismutase (SOD), a key antioxidant enzyme depleted by UV exposure.","whyItMatters":"Getting peptides through the skin barrier is one of the biggest challenges in topical peptide therapy — most peptides are too large to penetrate effectively. This study tackles that problem with a microemulsion gel system that significantly improves skin penetration. The fact that a gecko-derived cathelicidin shows anti-photoaging effects (not just antimicrobial activity) expands our understanding of what cathelicidin peptides can do, while the delivery system could potentially be applied to other therapeutic peptides.","specificNumbers":"","methodology":"Researchers formulated the gecko-derived peptide G3CY-10 into a microemulsion gel using a lecithin-ethanol-butyl acetate system and tested its stability and transdermal delivery efficiency. They then exposed mice to UV radiation to induce photoaging and applied the peptide gel topically. Outcomes were assessed by measuring epidermal thickness, sebaceous gland proliferation, collagen fiber density (via Masson staining), collagen degradation markers, and superoxide dismutase levels.","limitations":"This is a mouse study — human skin structure and thickness differ significantly from murine skin, which may affect transdermal delivery results. The study does not report long-term safety data for the peptide or the microemulsion vehicle. No comparison was made against established anti-photoaging treatments like retinoids or vitamin C. The specific UV exposure protocol may not fully replicate natural sun exposure patterns."},{"rthcId":"RPEP-14082","title":"Nanoparticles with Cell-Penetrating Peptides for Oral Delivery: A Case for Oral Delivery of Insulin.","authors":"Wang, Yunyun; Song, Wangdi; Wang, Taiyu; Sheng, Yue; Xue, Shengnan; Dang, Yanyan; Rasool, Aamir; Zhang, Genlin","year":2025,"journal":"International journal of nanomedicine, 20, 14283-14312","doi":"10.2147/IJN.S529791","pmid":"41347032","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14083","title":"Identification and characterization of vasoactive intestinal peptide receptor antagonists with high-affinity and potent anti-leukemia activity.","authors":"Wang, Yuou; Sen-Majumdar, Anish; Li, Jian-Ming; Sarkar, Srijon; Passang, Tenzin; Mecorapaj, Sonia; Balaji, Swapnaa; Kalsang, Tenzin; Ward, Antonio B; Li, Yiwen; Cohen, Jamie; Chen, Zihan; Chaudagar, Kiranj; Das, Pankoj Kumar; Wang, Shuhua; Bruk, Nabute; Papadantonakis, Nikolaos; Giver, Cynthia R; Waller, Edmund K","year":2025,"journal":"The Journal of biological chemistry, 302(3), 111127","doi":"10.1016/j.jbc.2025.111127","pmid":"41478571","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14084","title":"Computation strategies and clinical applications in neoantigen discovery towards precision cancer immunotherapy.","authors":"Wang, Zhenchang; Gu, Yu; Sun, Xiao; Huang, Hao","year":2025,"journal":"Biomarker research, 13(1), 96","doi":"10.1186/s40364-025-00808-9","pmid":"40629481","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14085","title":"Dual interference with host neuropeptide signaling allows parasitoid wasp to hijack host sugar metabolism.","authors":"Wang, Zhi-Zhi; Ma, Ruo-Fei; Gu, Li-Cheng; Wang, Li-Zhi; Chen, Ting; Yang, Pei; Zou, Jia-Ni; Zhu, Jiang-Yan; Wu, Zhi-Wei; Zhou, Yue-Nan; Shi, Min; Shen, Xing-Xing; Huang, Jian-Hua; Chen, Xue-Xin","year":2025,"journal":"The EMBO journal","doi":"10.1038/s44318-025-00636-5","pmid":"41299080","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14086","title":"Advances in Genetic Polymorphism Research in Rosacea: Mechanisms and Clinical Implications.","authors":"Wang, Zhuangyi; Zhang, Zhengzhong","year":2025,"journal":"Clinical, cosmetic and investigational dermatology, 18, 1423-1429","doi":"10.2147/CCID.S524611","pmid":"40496604","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies several key genes with polymorphisms associated with rosacea:\n\n- CAMP (cathelicidin antimicrobial peptide): Encodes the precursor of LL-37, an antimicrobial peptide whose overexpression drives rosacea-specific inflammation\n- TLR2 (Toll-like receptor 2): Part of innate immune recognition; variants may alter the skin's inflammatory response to microbes\n- IL-17: A pro-inflammatory cytokine gene associated with chronic inflammatory skin conditions\n- HLA (human leukocyte antigen): Immune system genes that determine susceptibility to various inflammatory conditions\n\nThe disease is characterized as polygenic with environmental modifiers, involving both innate immunity and neurovascular regulation abnormalities.","whyItMatters":"Rosacea affects up to 10% of people worldwide and currently has no cure. Understanding the genetic basis — particularly the role of the CAMP/cathelicidin gene that encodes an antimicrobial peptide — could transform treatment from symptom management to targeted intervention. Patients with specific CAMP gene variants might benefit from therapies that specifically modulate cathelicidin peptide production, like ivermectin.","specificNumbers":"","methodology":"Narrative review summarizing recent genetic association studies and polymorphism research in rosacea. The review covers candidate gene studies and potential genome-wide findings related to rosacea onset and progression.","limitations":"As a review, no original genetic data are presented. Many of the cited genetic associations come from relatively small studies that may not replicate across different ethnic populations. The review does not include genome-wide association study (GWAS) results at large scale. The functional consequences of most identified polymorphisms on peptide expression or activity have not been fully characterized."},{"rthcId":"RPEP-14087","title":"Peptide IRW upregulates ACE2 in spontaneously hypertensive rats via dopamine/D1R signaling pathway.","authors":"Wang, Zihan; Guan, Le Luo; Wu, Jianping","year":2025,"journal":"Journal of advanced research","doi":"10.1016/j.jare.2025.11.020","pmid":"41253272","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14088","title":"Transcriptomic and Lipidomic Analyses Reveal a Novel Antiapoptotic Mechanism of Peptide IRW in the Arteries of Spontaneously Hypertensive Rats through the Reduction of Ceramide Levels and Arachidonic Acid Release.","authors":"Wang, Zihan; Bao, Xiaoyu; Rivas-Serna, Irma Magaly; Lou, Yuanyuan; Mazurak, Vera C; Wu, Jianping","year":2025,"journal":"Journal of agricultural and food chemistry, 73(37), 23404-23416","doi":"10.1021/acs.jafc.5c07285","pmid":"40905398","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14089","title":"MultiCycPermea: accurate and interpretable prediction of cyclic peptide permeability using a multimodal image-sequence model.","authors":"Wang, Zixu; Chen, Yangyang; Shang, Yifan; Yang, Xiulong; Pan, Wenqiong; Ye, Xiucai; Sakurai, Tetsuya; Zeng, Xiangxiang","year":2025,"journal":"BMC biology, 23(1), 63","doi":"10.1186/s12915-025-02166-2","pmid":"40016695","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14090","title":"Thermosensitive-based synergistic antibacterial effects of novel LL37@ZPF-2 loaded poloxamer hydrogel for infected skin wound healing.","authors":"Wang, Zixuan; Sun, Yingxiao; Dong, Peijie; Wang, Jinhu; Wang, Lijie; Zhao, Aili; Qu, Guangmin; Li, Hang; Maheshika Gunarathne, Kannapathirage Dilini; Zhang, Wen; Chen, Yao; Meng, Xin","year":2025,"journal":"International journal of pharmaceutics, 670, 125210","doi":"10.1016/j.ijpharm.2025.125210","pmid":"39800001","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14091","title":"Predictors of weight reduction effectiveness with liraglutide in diabetes mellitus type 2 patients: a retrospective cohort study.","authors":"Wangpattanamongkol, Pitsinee; Manosroi, Worapaka","year":2025,"journal":"BMC endocrine disorders, 25(1), 240","doi":"10.1186/s12902-025-02066-0","pmid":"41131486","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14092","title":"The Ozempic Generation: What the Interventional Radiologist Needs to Know About GLP-1 Agonists.","authors":"Wani, Suhail; Findakly, Salam; Phan, Tuan; Lukies, Matthew W; Goh, Gerard S; Venn, Georgina; Joseph, Tim; Koukounaras, Jim; Clements, Warren","year":2025,"journal":"Journal of medical imaging and radiation oncology, 69(8), 836-843","doi":"10.1111/1754-9485.70045","pmid":"41239945","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies two primary peri-procedural concerns for patients taking GLP-1 receptor agonists:\n\n1. Delayed gastric emptying — GLP-1 agonists slow the rate at which the stomach empties, meaning standard fasting protocols may not adequately ensure an empty stomach before conscious sedation, increasing the risk of aspiration (inhaling stomach contents into the lungs)\n\n2. Blood sugar effects — These drugs lower fasting glucose levels, which has implications for blood sugar management during and after procedures, particularly in diabetic patients who may also be on insulin or other hypoglycemic agents\n\nThe review emphasizes that current interventional radiology guidelines do not adequately address these GLP-1-specific risks and calls for IR-specific guidance to be developed.","whyItMatters":"With GLP-1 agonist prescriptions skyrocketing for both diabetes and weight management, virtually every medical specialty is now encountering patients on these drugs. The sedation safety concern is particularly urgent because delayed gastric emptying is a well-documented effect of GLP-1 agonists, and aspiration during sedation can be life-threatening. Updated pre-procedure protocols could prevent serious complications as more patients present for interventional radiology procedures while taking these medications.","specificNumbers":"","methodology":"This is a narrative review discussing the pharmacological effects of GLP-1 receptor agonists and their implications for interventional radiology practice. The authors synthesize existing literature on GLP-1 drug pharmacology, gastric emptying effects, and peri-procedural management to identify gaps in current clinical guidelines.","limitations":"This is a narrative review focused on interventional radiology, and the specific evidence base for aspiration risk in GLP-1 patients undergoing IR procedures is limited. Most sedation safety data comes from surgical and anesthesia literature. The degree of gastric emptying delay varies between different GLP-1 agonists, doses, and individual patients, making blanket recommendations difficult. The review does not present original data or systematic evidence synthesis."},{"rthcId":"RPEP-14093","title":"Fish By-Products Utilization in Food and Health: Extraction Technologies, Bioactive, and Sustainability Challenges.","authors":"Waqar, Muhammad; Sajjad, Nimra; Ullah, Qudrat; Vasanthkumar, S S; Ahmed, Faiyaz; Panpipat, Worawan; Aluko, Rotimi E; Kaur, Lovedeep; Chaijan, Manat; Ageru, Temesgen Anjulo","year":2025,"journal":"Food science & nutrition, 13(11), e71184","doi":"10.1002/fsn3.71184","pmid":"41234609","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14094","title":"Efficacy of GLP-1 receptor agonists among older adults: a meta-analysis of cardio-kidney outcome trials.","authors":"Waqas, Saad Ahmed; Ali, Dua; Afridi, Muhammad Khalid; Siddiqui, Hasan Fareed; Nazir, Arif; Greene, Stephen J; Khan, Muhammad Shahzeb","year":2025,"journal":"Archives of gerontology and geriatrics, 138, 105981","doi":"10.1016/j.archger.2025.105981","pmid":"40812084","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 44,013 older adults (≥65 years) across 11 randomized controlled trials, GLP-1 receptor agonists significantly reduced:\n- Composite kidney outcome by 22% (HR: 0.78; 95% CI: 0.70-0.87; P < 0.001)\n- 3-point major adverse cardiovascular events (MACE) by 14% (HR: 0.86; approximate from context)\n- Cardiovascular death by 13%\n\nBenefits on stroke, myocardial infarction, and heart failure hospitalization showed favorable trends but did not reach statistical significance individually. Importantly, the efficacy in older adults was comparable to younger adults, with no significant interaction between age groups (P > 0.2 for all endpoints).","whyItMatters":"Older adults bear the greatest burden of cardiovascular and kidney disease but clinicians often hesitate to prescribe newer medications due to limited evidence in this age group. This meta-analysis — with over 44,000 older participants — provides the strongest evidence yet that GLP-1 receptor agonists are effective and safe in older adults. The consistent benefits across age groups should reassure clinicians that these peptide drugs work just as well for their older patients.","specificNumbers":"","methodology":"Systematic review and meta-analysis following PRISMA guidelines. Eleven randomized controlled trials were included, encompassing 85,373 total participants (51.6% older adults ≥65 years). Outcomes assessed included composite kidney outcome, 3-point MACE, cardiovascular death, stroke, myocardial infarction, and heart failure hospitalization. Hazard ratios were pooled using a random-effects model. Subgroup analysis compared efficacy between older (≥65) and younger (<65) adults.","limitations":"The 65-year age cutoff is relatively young for geriatric medicine; data on adults ≥75 or ≥80 may be more limited. Individual trial definitions of kidney outcomes may vary. The meta-analysis could not assess specific GLP-1RA agents separately due to the pooled approach. Some individual endpoints (stroke, MI, HHF) did not reach significance, possibly due to insufficient power even in this large analysis. Safety outcomes specific to older adults (falls, frailty, sarcopenia from weight loss) were not the primary focus."},{"rthcId":"RPEP-14095","title":"Recurrent weight gain after sleeve gastrectomy: conversion to Roux-en-Y gastric bypass versus novel GLP-1 s.","authors":"Wasden, Katherine; Mathur, Vasundhara; Martin, Thomas J; Shin, Thomas H; Nimeri, Abdelrahman A; Tavakkoli, Ali; Sheu, Eric G","year":2025,"journal":"Surgical endoscopy, 39(8), 5303-5314","doi":"10.1007/s00464-025-11910-2","pmid":"40603615","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14096","title":"Semaglutide - properties, action and chromatographic analysis.","authors":"Wasilewska, Barbara; Petruczynik, Anna","year":2025,"journal":"Journal of diabetes and metabolic disorders, 24(2), 197","doi":"10.1007/s40200-025-01711-8","pmid":"40937273","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14097","title":"Integrating computational design with crystallographic validation.","authors":"Watson, Paris R; Pardo-Avila, Fátima; Hosseinzade, Parisa","year":2025,"journal":"Methods in enzymology, 723, 111-124","doi":"10.1016/bs.mie.2025.08.030","pmid":"41266029","tags":[],"studyType":"methods","evidenceStrength":"low","keyFinding":"Researchers developed a reproducible computational workflow for designing cyclic peptide drugs that combines Rosetta protein modeling, molecular dynamics simulations, chemical synthesis, and X-ray crystallography validation. Using the 'anchor extension' method — starting from an unnatural amino acid known to bind the target and computationally extending the cyclic peptide scaffold — they found high-affinity, selective inhibitors by testing fewer than 50 designed peptides.\n\nThe method uses a chemical space of all canonical amino acids, their mirror-image variants, and 20 non-canonical amino acids. Originally developed for histone deacetylase (HDAC) inhibitors, the approach has been successfully extended to other targets including kappa-opioid receptors.","whyItMatters":"Cyclic peptides are among the most promising new drug classes — they can target 'undruggable' protein-protein interactions that small molecules can't reach. But designing them computationally has been extremely difficult because of their conformational complexity. This workflow makes the process systematic and reproducible, potentially accelerating the discovery of cyclic peptide drugs across many disease areas.","specificNumbers":"Fewer than 50 designed peptides tested to find high-affinity hits · Chemical space: all 20 amino acids + chiral variants + 20 non-canonical amino acids · Applied to HDACs and kappa-opioid receptors","methodology":"The protocol describes the anchor extension method: (1) starting with a known binding anchor (unnatural amino acid), (2) computationally extending the cyclic peptide using generalized kinematic loop closure in Rosetta, (3) refining with molecular dynamics simulations, (4) synthesizing top candidates, and (5) validating binding with X-ray crystallography. The workflow is designed to be generalizable across different protein targets.","limitations":"This is a methods paper describing a design protocol — it does not present new biological or clinical data. The efficiency of the approach (hits from <50 designs) is demonstrated for specific targets (HDACs, kappa-opioid receptors) and may vary for other protein classes. The designed peptides' drug-like properties (oral bioavailability, stability, toxicity) are not addressed."},{"rthcId":"RPEP-14098","title":"Virtual Screening of Cathelicidin-Derived Anticancer Peptides and Validation of Their Production in the Probiotic Limosilactobacillus fermentum KUB-D18 Using Genome-Scale Metabolic Modeling and Experimental Approaches.","authors":"Wattayagorn, Vichugorn; Mansuwan, Taratorn; Angkanawin, Krittapas; Sapkaew, Chakkapan; Sinthuvanich, Chomdao; Watthanasakphuban, Nisit; Chumnanpuen, Pramote","year":2025,"journal":"International journal of molecular sciences, 26(20)","doi":"10.3390/ijms262010077","pmid":"41155367","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14099","title":"Pretreatment with an anti-CGRP monoclonal antibody attenuates mild TBI-induced tactile hypersensitivity in mice.","authors":"Wattiez, Anne-Sophie; Kuburas, Adisa; Castonguay, William C; Fejgin, Kim; Klewe, Ib V; Russo, Andrew F","year":2025,"journal":"The journal of headache and pain, 26(1), 175","doi":"10.1186/s10194-025-02108-x","pmid":"40760469","tags":[],"studyType":"animal study","evidenceStrength":"low","keyFinding":"An anti-CGRP monoclonal antibody partially reduced persistent headache-like sensitivity following mild traumatic brain injury (concussion) in mice. When given before or immediately after repeated head impacts, the antibody partially reduced ongoing tactile hypersensitivity but did not fully prevent it. However, when administered before exposure to headache triggers (CGRP itself or nitric oxide) during the persistent sensitization phase, the antibody fully prevented hypersensitivity. This suggests anti-CGRP therapy may be most effective at blocking the triggers that maintain post-traumatic headache rather than preventing the initial injury response.","whyItMatters":"Post-traumatic headache (PTH) following concussion is extremely common in military personnel, veterans, and athletes, and can become chronic and debilitating. Current treatments are largely borrowed from migraine therapy without strong evidence. This study provides the first preclinical evidence that the timing of anti-CGRP antibody administration matters critically: the antibody works best not at preventing the initial head-injury response, but at blocking the ongoing triggers that keep pain sensitization alive. This could guide how these drugs are used clinically in concussion patients.","specificNumbers":"3 repeated closed head impacts · Partial reduction of periorbital hypersensitivity · Full prevention of trigger-induced hypersensitivity during persistent phase","methodology":"Researchers used outbred CD1 mice subjected to three repeated closed head impacts to model mild TBI. They tested anti-CGRP monoclonal antibody administration at different timepoints: before injury, immediately after injury, and before headache triggers (CGRP injection or sodium nitroprusside/nitric oxide donor) during the persistent sensitization phase. Periorbital and plantar tactile hypersensitivity were measured as surrogate markers for headache-related pain sensitivity.","limitations":"Mouse models of TBI and headache rely on surrogate pain measures (tactile sensitivity) that may not directly correspond to human headache experience. The model uses repeated impacts rather than a single concussion, which may not reflect all clinical scenarios. The study doesn't address whether anti-CGRP treatment would affect cognitive or other post-concussion outcomes. Translation to human TBI timing and dosing requires clinical trials. The antibody used is not specified as any particular clinical anti-CGRP drug."},{"rthcId":"RPEP-14100","title":"Incretin signaling at the crossroads of metabolism, inflammation, and tumorigenesis: implications for obesity patients.","authors":"Wawrzak-Pienkowska, Katarzyna; Pienkowski, Tomasz; Golonko, Aleksandra; Krupa, Anna; Warpechowski, Marcin; Plonski, Adam Filip; Mojsak, Patrycja; Daniluk, Jaroslaw; Dabrowski, Andrzej; Kurek, Krzysztof","year":2025,"journal":"European journal of pharmacology, 1007, 178290","doi":"10.1016/j.ejphar.2025.178290","pmid":"41138841","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14101","title":"Specific loss of GIPR signaling in GABAergic neurons enhances GLP-1R agonist-induced body weight loss.","authors":"Wean, Jordan; Kowalsky, Allison Ho; Laker, Rhianna; Will, Sarah; Drucker, Daniel J; Rhodes, Christopher J; Seeley, Randy J","year":2025,"journal":"Molecular metabolism, 95, 102074","doi":"10.1016/j.molmet.2024.102074","pmid":"39612941","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14102","title":"Development of a novel alpha7-nicotinic acetylcholine receptor-selective cell-penetrating peptide for intracellular cargo transport.","authors":"Weber, Lahra; O'Brien, Brittany C V; Weltzin, Maegan M","year":2025,"journal":"Drug delivery, 32(1), 2587378","doi":"10.1080/10717544.2025.2587378","pmid":"41319151","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14103","title":"Development of a novel alpha7-nicotinic acetylcholine receptor-selective cell-penetrating peptide for intracellular cargo transport.","authors":"Weber, Lahra; O'Brien, Brittany C V; Weltzin, Maegan M","year":2025,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2025.08.08.669423","pmid":"41030997","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The researchers designed chimeric peptides combining regions of rabies virus glycoprotein (RVG) and alpha-bungarotoxin, then screened them for receptor selectivity. They identified a peptide with improved selectivity and apparent potency for the alpha-7 nicotinic acetylcholine receptor (nAChR) subtype compared to the control RVG peptide. In Neuro-2a cells, the peptide's internalization depended on alpha-7 nAChR expression on the cell surface, and it successfully carried small-molecule payloads into neuronal-like cells without significant cytotoxic effects.","whyItMatters":"Current brain drug delivery peptides lack target specificity, meaning they spread throughout the brain and cause off-target side effects. A peptide that selectively uses alpha-7 nicotinic receptors as its entry point could enable more precise delivery of therapeutics to specific brain cell populations. Alpha-7 nAChRs are implicated in Alzheimer's disease, schizophrenia, and other neurological conditions, making this a strategically important target for dual-purpose drug delivery.","specificNumbers":"","methodology":"Researchers designed several chimeric peptides and tested their selectivity using human nicotinic acetylcholine receptors expressed in Xenopus laevis oocytes with two-electrode voltage clamp electrophysiology — a technique that measures receptor responses to peptide binding. They then tested the lead peptide's ability to enter cells and deliver cargo using mammalian Neuro-2a cells (a neuronal cell line), assessing internalization, payload delivery, and cytotoxicity.","limitations":"This is a preprint (bioRxiv) that has not yet been peer-reviewed. All experiments were conducted in vitro using frog oocytes and a neuronal cell line — there are no in vivo blood-brain barrier crossing data. The small-molecule cargo delivery was demonstrated but therapeutic payloads were not tested. Whether the selectivity observed in controlled cell systems translates to the complex environment of the intact brain remains unknown."},{"rthcId":"RPEP-14104","title":"Calcitonin gene-related peptide concentration in cerebrospinal fluid and serum in horses affected by trigeminal-mediated headshaking.","authors":"Weber, Lisa Annabel; Oltmanns, Hilke; Chiavaccini, Ludovica; Pickles, Kirstie J; Roberts, Veronica; Kloock, Tanja; Niebuhr, Tobias; Feige, Karsten","year":2025,"journal":"Equine veterinary journal","doi":"10.1002/evj.70139","pmid":"41416948","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14105","title":"Novel Synthetic Strategies Towards Analogues of Cadaside and Malacidin Antibiotic Peptides.","authors":"Webhofer, Katharina; Naidu, Darsha; Karak, Milandip; Cochrane, Stephen A; Morris, Christopher J; Dickman, Rachael","year":2025,"journal":"Biomolecules, 15(11)","doi":"10.3390/biom15111497","pmid":"41301415","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14106","title":"Identification and characterization of umami-ACE inhibitory peptides from traditional fermented soybean curds.","authors":"Wei, Guanmian; Zhao, Feiran; Zhang, Ziyi; Regenstein, Joe M; Sang, Yaxin; Zhou, Peng","year":2025,"journal":"Food chemistry, 465(Pt 2), 142160","doi":"10.1016/j.foodchem.2024.142160","pmid":"39579405","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"From fermented soybean curds, 11 candidate peptides with potential dual umami and ACE inhibitory activities were identified via nano-HPLC-MS/MS and database screening. Pharmacophore modeling confirmed high ACE inhibition probability (fit values >2) with binding through hydrogen bonds, electrostatic, and hydrophobic interactions.\n\nThree synthesized peptides showed the following ACE inhibitory IC50 values: WEEF (85 ± 2 μM), FEF (170 ± 10 μM), and VE (205 ± 5 μM). Umami thresholds were WEEF (0.32 mM) < FEF (0.53 mM) < VE (4.8 mM). WEEF exhibited the best overall dual activity. Nitric oxide (NO) and endothelin-1 (ET-1) production were dose-dependent, further supporting vascular activity.","whyItMatters":"The food industry is seeking natural ingredients that combine health benefits with desirable flavors. Peptides that simultaneously enhance taste (umami) and lower blood pressure (ACE inhibition) represent a particularly valuable class of functional food ingredients. Fermented soybean products are already widely consumed, making these peptides immediately relevant for developing 'functional foods' that taste good while providing cardiovascular benefits — without needing pharmaceutical drugs.","specificNumbers":"","methodology":"Peptides were identified from fermented soybean curds using nano-HPLC-MS/MS. Candidates were screened for umami and ACE inhibitory potential using bioinformatics databases. Pharmacophore model analysis, molecular docking, and interaction energy calculations were performed. Three top candidates (VE, FEF, WEEF) were chemically synthesized and tested for ACE inhibitory activity (IC50), umami taste thresholds, and effects on NO and ET-1 production.","limitations":"ACE inhibition was demonstrated in vitro and through computational modeling, not in animal or human studies. The IC50 values (85-205 μM) are moderate compared to pharmaceutical ACE inhibitors. Whether these peptides survive gastrointestinal digestion to reach systemic circulation is unknown. The umami taste evaluation methodology and panel details are not described in the abstract. NO and ET-1 effects were measured in cell-based assays, not in vivo blood pressure studies."},{"rthcId":"RPEP-14107","title":"Deficiency of NPR-C triggers high salt-induced thoracic aortic dissection by impairing mitochondrial homeostasis.","authors":"Wei, Jin-Qiu; Yang, Yi; Zhai, Wen-Hui; Zhao, Jia-Jia; Yang, Yi-Hang; Kang, Yuan-Yuan; Huang, Qi-Fang; Zhang, Wei; Rong, Wu-Wei; Deng, Qian-Wan; Chen, Jing; Ye, Xiao-Fei; Gao, Ping-Jin; Wang, Zhe; Li, Xiao-Dong; Wang, Ji-Guang","year":2025,"journal":"Cardiovascular research, 121(7), 1121-1134","doi":"10.1093/cvr/cvaf085","pmid":"40377018","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"NPR-C was downregulated in aortas of acute thoracic aortic dissection (TAD) patients and in mouse models. Smooth muscle cell-specific NPR-C knockout mice developed TAD when treated with angiotensin II plus high salt diet, but not angiotensin II alone — revealing high salt as a critical trigger.\n\nMechanistically, NPR-C loss activated the ERK1/2 pathway, which decreased PPARγ activity and suppressed HADHB expression, impairing mitochondrial fatty acid oxidation. The NPR-C agonist peptide C-ANP4-23 mitigated TAD progression in disease model mice, and spermidine (which activates the mitochondrial trifunctional protein) also effectively prevented TAD formation.","whyItMatters":"Aortic dissection kills up to 50% of patients and currently has no effective pharmacological prevention or treatment. This study identifies NPR-C as a protective factor and demonstrates that a peptide agonist can prevent disease progression. It also reveals that high salt intake is a critical environmental trigger — a modifiable risk factor that could inform dietary recommendations for at-risk individuals.","specificNumbers":"","methodology":"Researchers analyzed human TAD transcriptome and single-cell sequencing datasets to identify NPR-C downregulation. They generated vascular smooth muscle cell-specific and endothelial cell-specific NPR-C knockout mice, treating them with angiotensin II with or without high salt diet. RNA-sequencing identified affected pathways. Mechanistic studies examined the ERK1/2-PPARγ-HADHB signaling axis. Therapeutic potential was tested using the NPR-C agonist peptide C-ANP4-23 and spermidine in mouse models.","limitations":"This is a preclinical study using genetically modified mice, which may not fully replicate human aortic dissection. The BAPN-induced and angiotensin II-induced mouse models are widely used but do not capture all aspects of human disease. The therapeutic effects of C-ANP4-23 and spermidine were demonstrated only in mice. The study did not address long-term safety or optimal dosing of NPR-C agonists. Human genetic studies linking NPR-C variants to aortic dissection risk would strengthen the translational relevance."},{"rthcId":"RPEP-14108","title":"Microfluidic Regulation of Core-Shell PLGA Microspheres for Sustained Release of Leuprolide Acetate.","authors":"Wei, Ruoxin; Dou, Jiaze; Wu, Yihui; Li, Jinjin; Cen, Lian; Xi, Zhenhao","year":2025,"journal":"Langmuir : the ACS journal of surfaces and colloids, 41(27), 17893-17901","doi":"10.1021/acs.langmuir.5c01667","pmid":"40605279","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Using a glass capillary microfluidic device, researchers produced monodisperse PLGA microspheres with a uniform particle size of 80 μm and a distinct core-shell structure for leuprolide acetate delivery. At an optimal gelatin concentration of 7.5 mg/mL in the inner aqueous phase, microspheres achieved maximum encapsulation efficiency of 80.28% and drug loading of 4.24%.\n\nThe microspheres sustained leuprolide release for approximately 28 days in vitro. Drug loading increased proportionally with leuprolide concentration in the inner phase. Gelatin incorporation and collecting solution pH were identified as the critical factors controlling encapsulation efficiency.","whyItMatters":"Current leuprolide microsphere products (like Lupron Depot) are made using conventional emulsification techniques that produce particles of varying sizes, which can lead to inconsistent drug release. Microfluidic manufacturing creates extremely uniform particles, potentially improving the predictability and consistency of drug delivery. This technology could be applied to many other peptide and protein drugs that need sustained release, advancing the field of injectable depot formulations.","specificNumbers":"","methodology":"Researchers developed a glass capillary microfluidic device to generate water-in-oil-in-water (W/O/W) emulsions that solidified into PLGA microspheres. They systematically varied gelatin concentration in the internal aqueous phase, collecting solution composition, and leuprolide concentration to optimize encapsulation. Microsphere morphology was characterized for size uniformity and core-shell structure. In vitro drug release was measured over 28 days.","limitations":"This is an in vitro study only — no animal testing was performed to confirm that the 28-day release profile translates to sustained drug levels in vivo. Microfluidic production rates are typically much slower than conventional methods, which could limit commercial scalability. The 80 μm particle size is relatively large for injection, and injectability was not assessed. Comparison with commercially available leuprolide microsphere products was not included."},{"rthcId":"RPEP-14109","title":"AI-Driven De Novo Design of Ultra Long-Acting GLP-1 Receptor Agonists.","authors":"Wei, Ting; Ma, Jiating; Cui, Xiaochen; Lin, Jiahui; Zheng, Zhuoqi; Cheng, Liu; Cui, Taiying; Lin, Xiaoqian; Zhu, Junjie; Ran, Xuyang; Hong, Xiaokun; Johnston, Luke; Yu, Zhangsheng; Chen, Haifeng","year":2025,"journal":"Advanced science (Weinheim, Baden-Wurttemberg, Germany), 12(40), e07044","doi":"10.1002/advs.202507044","pmid":"40787887","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14110","title":"Aza-Isotryptophan: Synthesis, Pictet-Spengler Chemistry, Incorporation and Conformational Analysis in Peptides, and Activity in Modulators of the Cluster of Differentiation-36 Receptor.","authors":"Wei, Xiaozheng; Mulumba, Mukandila; Chemtob, Sylvain; Ong, Huy; Lubell, William D","year":2025,"journal":"Journal of medicinal chemistry, 68(21), 22738-22755","doi":"10.1021/acs.jmedchem.5c01693","pmid":"41151018","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14111","title":"Short-term prognosis of patients in different stages of severe tricuspid regurgitation after transcatheter tricuspid-valve replacement.","authors":"Wei, Xin; Li, Xi; Qiao, Fan; Zhang, Yi; Feng, Yuan; Zhao, Zhengang; Liang, Yujia; Xiong, Tianyuan; Chen, Fei; Ji, Xingyu; Ge, Junbo; Lu, Fanglin; Chen, Mao","year":2025,"journal":"Quantitative imaging in medicine and surgery, 15(8), 7155-7168","doi":"10.21037/qims-2024-2692","pmid":"40785858","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14112","title":"Integrated network pharmacology and experimental validation to explore the mechanisms of Coregonus peled-derived myosin ACE-inhibiting peptides for the treatment of hypertension.","authors":"Wei, Yabo; Wang, Zhouping; Guo, Xin; Lei, Yongdong; Deng, Xiaorong; Zhang, Jian","year":2025,"journal":"International journal of biological macromolecules, 284(Pt 2), 138218","doi":"10.1016/j.ijbiomac.2024.138218","pmid":"39617224","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14113","title":"Membrane Tethering of Honeybee Antimicrobial Peptides in Drosophila Enhances Pathogen Defense at the Cost of Stress-Induced Host Vulnerability.","authors":"Wei, Yanan; Sun, Yanying; Zhou, Xinyue; Kim, Doyoun; Lee, Jihyeon; Bang, Jeong Kyu; Kim, Woo Jae","year":2025,"journal":"Chembiochem : a European journal of chemical biology, 26(20), e202500271","doi":"10.1002/cbic.202500271","pmid":"41147140","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tethering honeybee defensin-1 (Def1) to cell membranes via a GPI anchor in Drosophila flies boosted antimicrobial potency by approximately 100-fold compared to secreted or untethered forms. Flies with membrane-tethered Def1 showed superior clearance of Pseudomonas aeruginosa and improved survival after infection, with no adverse effects on movement, mating behavior, or sleep under normal conditions.\n\nHowever, under stress conditions — sleep deprivation and chemically induced gut injury — the tethered peptide worsened intestinal barrier damage. This reveals a fundamental trade-off: anchoring antimicrobial peptides to membranes dramatically increases their killing power but can make the host's gut lining more vulnerable during stress.","whyItMatters":"Antimicrobial peptides are among the most promising alternatives to failing antibiotics, but three problems block their clinical use: enzymes destroy them, they can harm host cells, and they don't stay where they're needed. Membrane tethering solves all three by anchoring the peptide where it fights bacteria. The 100-fold potency increase is remarkable, but the stress-related gut vulnerability reveals an important safety consideration that must be addressed before translating this approach to human therapeutics.","specificNumbers":"~100-fold potency increase · Superior P. aeruginosa clearance · No baseline behavioral effects · Gut barrier dysfunction under stress · 3 Def1 variants tested (native, secreted, tethered)","methodology":"Researchers genetically engineered Drosophila melanogaster (fruit flies) to express three variants of honeybee defensin-1: native, secreted (s-Def1), and membrane-tethered via GPI anchor (t-Def1). Antimicrobial efficacy was tested by infecting flies with Pseudomonas aeruginosa and measuring bacterial clearance and survival. Behavioral impacts were assessed through locomotion, courtship, and sleep analysis. Stress vulnerability was tested using sleep deprivation and DSS-induced gut injury, with intestinal barrier integrity measured by Smurf assay.","limitations":"Drosophila is a useful model organism but differs significantly from mammals in immune system complexity, gut architecture, and physiology. The gut vulnerability under stress is concerning but was only tested under artificial stress conditions. The study does not address how membrane tethering would be achieved in mammalian systems. Only one AMP (Def1) and one pathogen (P. aeruginosa) were tested."},{"rthcId":"RPEP-14114","title":"Comparative cardiovascular outcomes and safety of hypoglycemic drug classes in patients with type 2 diabetes and hypertension: a multicenter cohort analysis.","authors":"Wei, Zhiyuan; Xu, Wanqian; Wang, Yu; Tian, Yu; Wang, Zhongmin; Jing, Shenqi; Liu, Weina; Shen, Sipeng; Qin, Chenlong; Zhang, Xin; Li, Jingsong; Liu, Yun","year":2025,"journal":"Cardiovascular diabetology, 24(1), 343","doi":"10.1186/s12933-025-02892-5","pmid":"40836299","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14115","title":"How 'miracle' weight-loss semaglutide promises to change medicine but can we afford the expense?","authors":"Weiskirchen, Ralf; Lonardo, Amedeo","year":2025,"journal":"British journal of pharmacology, 182(8), 1651-1670","doi":"10.1111/bph.70003","pmid":"39947645","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14116","title":"Semaglutide from Bench to Bedside: The Experimental Journey Towards a Transformative Therapy for Diabetes, Obesity and Metabolic Liver Disorders.","authors":"Weiskirchen, Ralf; Lonardo, Amedeo","year":2025,"journal":"Medical sciences (Basel, Switzerland), 13(4)","doi":"10.3390/medsci13040265","pmid":"41283266","tags":[],"studyType":"review","evidenceStrength":"strong","keyFinding":"Semaglutide's development from concept to blockbuster therapy was driven by strategic molecular engineering — amino acid substitutions and a C18 fatty-diacid side chain that extended the peptide's half-life to approximately 160 hours, enabling once-weekly dosing. The SUSTAIN clinical program demonstrated significant HbA1c reductions and weight loss compared to other treatments, plus a 26% decrease in the relative risk of major adverse cardiovascular events (SUSTAIN-6). The STEP trials expanded semaglutide's use to chronic weight management, showing nearly two-thirds of patients achieved at least 15% body weight reduction.\n\nOptimal weekly doses were established at 0.5 mg and 1.0 mg in phase II trials. Regulatory approvals from the FDA, EMA, and other agencies were obtained between 2017 and 2021.","whyItMatters":"Semaglutide has become one of the most consequential peptide drugs ever developed, transforming treatment for type 2 diabetes and obesity simultaneously. Its story demonstrates how deliberate peptide engineering can overcome the traditional limitations of peptide therapeutics — short half-life and poor oral bioavailability. With ongoing research into metabolic liver disease, cardiovascular events, and chronic kidney disease, semaglutide's therapeutic reach continues to expand.","specificNumbers":"Half-life: ~160 hours · Weekly doses: 0.5 mg and 1.0 mg · 26% reduction in major cardiovascular events (SUSTAIN-6) · ~65% of patients lost ≥15% body weight (STEP) · Approved 2017–2021","methodology":"This is a comprehensive narrative review analyzing preclinical datasets, phase I–III clinical trials, regulatory documents, and pharmacoepidemiological studies published between 2008 and 2025. The review covers the full translational pipeline from medicinal chemistry and animal studies through the pivotal SUSTAIN and STEP trial programs to post-marketing real-world surveillance.","limitations":"As a narrative review, this paper synthesizes existing data rather than presenting new primary research. The review scope is limited to published literature through 2025 and may not capture the most recent real-world outcomes or ongoing trial results for newer indications like MASH and chronic kidney disease."},{"rthcId":"RPEP-14117","title":"A real-world pharmacovigilance study of FDA adverse event reporting system events for atogepant.","authors":"Wen, Heli; Ding, Yitian; Chen, Feichi","year":2025,"journal":"Expert opinion on drug safety, 24(6), 745-752","doi":"10.1080/14740338.2024.2377347","pmid":"38970172","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"From 3,552,072 total FAERS reports, 2,876 specifically named atogepant. Women constituted the majority of reporters, concentrated in the 45–65 age group. The top adverse events by significant signal detection included expected effects: migraine (paradoxical worsening), constipation, nausea, vertigo, somnolence, decreased appetite, dizziness, and fatigue.\n\nNotably, unexpected adverse event signals were detected for: abnormal dreams, self-injurious ideation, brain fog, tension headache, nightmares, brain neoplasm (likely coincidental), feeling abnormal, euphoric mood, hyperacusis (heightened sound sensitivity), and post-concussion syndrome. All signals were confirmed across four independent detection algorithms (ROR, PRR, BCPNN, EBGM).","whyItMatters":"CGRP-blocking drugs are the first migraine treatments specifically targeting the peptide pathway underlying migraine pathophysiology, and atogepant is one of the newest oral options. As millions begin using these drugs, identifying unexpected neuropsychiatric effects — especially self-injurious ideation — is critical for patient safety. The detection of mood and cognitive effects suggests CGRP peptide signaling may play broader roles in brain function than previously appreciated.","specificNumbers":"","methodology":"Researchers extracted adverse event data from the FDA Adverse Event Reporting System (FAERS), the largest spontaneous adverse event database in the United States. Four established pharmacovigilance algorithms were applied: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayes Geometric Mean (EBGM). Signals were considered significant when all four algorithms agreed. Demographic patterns and system organ class distributions were analyzed.","limitations":"FAERS data has well-known limitations: reporting is voluntary and subject to reporting bias, reports don't prove causation (only association), and the database lacks denominator data (total number of patients taking the drug). The 'brain neoplasm' signal is almost certainly coincidental rather than causal. Some unexpected signals may reflect off-label use or pre-existing conditions. The statistical signals require clinical validation through controlled studies before being considered confirmed adverse effects."},{"rthcId":"RPEP-14118","title":"Beyond lifestyle modification: the role of GLP-1 receptor agonists in treating pediatric obesity.","authors":"Wen, Hua","year":2025,"journal":"Frontiers in pediatrics, 13, 1684485","doi":"10.3389/fped.2025.1684485","pmid":"41641128","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14119","title":"Ropivacaine combined with esketamine in ultrasound-guided thoracic paravertebral nerve block in lung cancer patients undergoing thoracoscopic radical surgery.","authors":"Wen, Jian; Zhou, Gao; Bin, Yong; Zeng, Yan; Tan, Dianxiang; Zhang, Juan","year":2025,"journal":"Discover oncology, 16(1), 1053","doi":"10.1007/s12672-025-02762-2","pmid":"40498250","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14120","title":"An exploratory analysis of glucagon-like peptide-1 (GLP-1) agonists and biosimilars: A literature review.","authors":"Wen, Jimmy; Razick, Adam; How-Volkman, Christiane; Bernstein, Ethan; Nadora, Denise; Truong, Alina; Razick, Daniel; Akhtar, Muzammil; Karabala, Muhammad; Frezza, Eldo","year":2025,"journal":"Diabetes, obesity & metabolism, 27(3), 1113-1122","doi":"10.1111/dom.16110","pmid":"39654073","tags":["glp-1-agonists","obesity-and-metabolism","drug-access-and-cost"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"The review found that liraglutide and semaglutide are the primary GLP-1 receptor agonists being targeted for biosimilar development. Preliminary clinical comparisons of liraglutide biosimilars to the reference product (Victoza/Saxenda) have demonstrated similar clinical efficacy and safety profiles, which is encouraging for regulatory approval.\n\nSemaglutide biosimilars and beinaglutide biosimilars are currently under active clinical investigation by pharmaceutical companies worldwide. The authors emphasize that without insurance, the monthly costs of these drugs — $1,418 for liraglutide, $892 for semaglutide, and $974 for tirzepatide — create a significant access barrier not only for diabetes and obesity patients but also for off-label uses like sleep apnea and fatty liver disease that benefit from weight loss.","whyItMatters":"The global demand for GLP-1 drugs has created one of the largest access crises in modern pharmaceuticals. Millions of patients who could benefit from these drugs — for diabetes, obesity, and emerging off-label uses — cannot afford or access them. Biosimilars represent the most realistic path to making these transformative medications widely available, similar to how generic statins democratized cholesterol treatment decades ago.","specificNumbers":"Liraglutide $1,418/mo · Semaglutide $892/mo · Tirzepatide $974/mo (without insurance) · Multiple biosimilar trials underway globally","methodology":"This was a narrative literature review that examined published studies and clinical trial data on GLP-1 receptor agonist biosimilar development. The authors reviewed the current pipeline of biosimilar candidates for liraglutide, semaglutide, and beinaglutide, as well as cost data and potential clinical applications.","limitations":"This is a narrative review, not a systematic review or meta-analysis. Most biosimilar data available is for liraglutide, with semaglutide biosimilars still in earlier stages of development. The review does not systematically compare all biosimilar candidates. Head-to-head trials between biosimilars and reference products are still needed for definitive conclusions. Cost figures may vary by market and change over time."},{"rthcId":"RPEP-14121","title":"Association Between Semaglutide or Tirzepatide Therapy and Residual Gastric Content: A Potential Danger During Upper Endoscopy.","authors":"Wen, Jimmy; Puglisi, Jose; Frezza, Eldo","year":2025,"journal":"Cureus, 17(11), e96771","doi":"10.7759/cureus.96771","pmid":"41393547","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14122","title":"Evaluating the Rates of Pancreatitis and Pancreatic Cancer Among GLP-1 Receptor Agonists: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.","authors":"Wen, Jimmy; Nadora, Denise; Bernstein, Ethan; How-Volkman, Christiane; Truong, Alina; Joy, Bethany; Kou, Megan; Muttalib, Zohaer; Alam, Arsh; Frezza, Eldo","year":2025,"journal":"Endocrinology, diabetes & metabolism, 8(5), e70113","doi":"10.1002/edm2.70113","pmid":"40988099","tags":[],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"This meta-analysis of 62 RCTs involving 66,232 patients found a statistically significant but small increased risk of pancreatitis with GLP-1 receptor agonists overall (RR: 1.44, 95% CI 1.09-1.89, p=0.009). However, this significance disappeared when stratified by background medication use — neither the with-background-medication group (RR: 1.28) nor the without-background-medication group (RR: 1.37) reached significance alone.\n\nFor pancreatic cancer, no overall significant association was found (RR: 1.30, 95% CI 0.86-1.97). A significant association appeared only in the subgroup taking background medications (RR: 1.85, p=0.03), but not without them. The authors note this difference is likely minimal given that many excluded studies had zero events in both arms.","whyItMatters":"With over 66,000 patients analyzed from RCTs spanning seven GLP-1 RAs (including semaglutide, tirzepatide, and retatrutide), this is the most comprehensive meta-analysis of pancreatic safety for these blockbuster peptide drugs. The results provide substantial reassurance — any pancreatitis risk is small and likely confounded by background medications, and pancreatic cancer risk is not significantly elevated.","specificNumbers":"","methodology":"Systematic review and meta-analysis following PRISMA guidelines, searching PubMed, Embase, and Cochrane Library. 62 RCTs were included covering dulaglutide, exenatide, liraglutide, semaglutide, beinaglutide, retatrutide, and tirzepatide. Mean patient age was 58.3 years with mean follow-up of 43.5 weeks. Risk ratios were calculated with subgroup analysis stratified by background medication use.","limitations":"Mean follow-up of 43.5 weeks may be insufficient to detect pancreatic cancer risk, which could require years of exposure. Many excluded studies had zero events in both arms, which could bias the analysis. Background medication confounding makes it difficult to isolate GLP-1 RA effects. The meta-analysis pools different GLP-1 RAs which may have different risk profiles."},{"rthcId":"RPEP-14123","title":"Exploring the Effects of Tirzepatide on Obstructive Sleep Apnea: A Literature Review.","authors":"Wen, Jimmy; Nadora, Denise; Truong, Alina; Bernstein, Ethan; How-Volkman, Christiane; Razick, Daniel I; Akhtar, Muzammil; Razick, Adam A; Frezza, Eldo","year":2025,"journal":"Cureus, 17(3), e80164","doi":"10.7759/cureus.80164","pmid":"40190919","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14124","title":"Next generation dual GLP-1/GIP, GLP-1/glucagon, and triple GLP-1/GIP/glucagon agonists: a literature review.","authors":"Wen, Jimmy; Nadora, Denise; Truong, Alina; Bernstein, Ethan; How-Volkman, Christiane; Razick, Adam; Razick, Daniel; Karabala, Muhammad; Frezza, Eldo","year":2025,"journal":"Nutrition, metabolism, and cardiovascular diseases : NMCD, 35(12), 104213","doi":"10.1016/j.numecd.2025.104213","pmid":"40685266","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14125","title":"Outcomes of Beinaglutide on Weight Loss in Patients With Diabetes or Obesity: A Systematic Review and Meta-Analysis.","authors":"Wen, Jimmy; Truong, Alina; Nadora, Denise; How-Volkman, Christiane; Bernstein, Ethan M; Kou, Megan; Alam, Arsh; Puglisi, Jose; Frezza, Eldo","year":2025,"journal":"Cureus, 17(12), e100224","doi":"10.7759/cureus.100224","pmid":"41607973","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14126","title":"The Potential of SARMs and Antimyostatin Agents in Addressing Lean Body Mass Loss From GLP-1 Agonists: A Literature Review.","authors":"Wen, Jimmy; Ansari, Ubaid; Shehabat, Mouhamad; Ansari, Zaid; Syed, Burhaan; Razick, Adam; Razick, Daniel; Akhtar, Muzammil; Frezza, Eldo","year":2025,"journal":"Journal of diabetes, 17(8), e70119","doi":"10.1111/1753-0407.70119","pmid":"40739991","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14127","title":"Tirzepatide Versus Semaglutide on Weight Loss in Type 2 Diabetes Patients: A Systematic Review and Meta-Analysis of Direct Comparative Studies.","authors":"Wen, Jimmy; Syed, Burhaan; Nadora, Denise; How-Volkman, Christiane; Bernstein, Ethan; Truong, Alina; Akhtar, Muzammil; Razick, Adam; Puglisi, Jose; Frezza, Eldo","year":2025,"journal":"Endocrinology, diabetes & metabolism, 8(3), e70045","doi":"10.1002/edm2.70045","pmid":"40184508","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14128","title":"Naturally inspired chimeric quinolone derivatives to reverse bacterial drug resistance.","authors":"Wen, Qi; He, Yuhang; Chi, Jiaying; Wang, Luyao; Ren, Yixuan; Niu, Xiaoke; Yang, Yanqing; Chen, Kang; Zhu, Qi; Lin, Juncheng; Xiang, Yanghui; Xie, Junqiu; Chen, Wenteng; Yu, Yongping; Wang, Baohong; Wang, Bo; Zhang, Ying; Lu, Chao; Wang, Kairong; Teng, Peng; Zhou, Ruhong","year":2025,"journal":"European journal of medicinal chemistry, 289, 117496","doi":"10.1016/j.ejmech.2025.117496","pmid":"40088661","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"IPMCL-28b, a chimeric ciprofloxacin derivative incorporating three cationic amino acids and a lipophilic n-decanoyl tail connected by a rigid linker, showed potent activity against multiple multidrug-resistant bacterial strains. It achieved a 99.99% (4.4 log) reduction in MRSA skin bacterial load after a single dose in mice. The compound demonstrated high selectivity with low hemolysis (minimal red blood cell damage), significantly reduced likelihood of resistance development compared to ciprofloxacin, and dual mechanism of action — retaining ciprofloxacin's DNA gyrase inhibition while gaining membrane-disrupting capability. Molecular dynamics simulations confirmed stronger membrane interactions than ciprofloxacin alone.","whyItMatters":"MRSA and other drug-resistant bacteria kill hundreds of thousands of people annually, and new antibiotic approaches are desperately needed. This peptide-mimicking strategy is particularly clever because it takes a proven antibiotic (ciprofloxacin) and gives it a second killing mechanism inspired by antimicrobial peptides — which bacteria have struggled to develop resistance against for millions of years. The dual-mechanism approach makes it much harder for bacteria to evolve resistance.","specificNumbers":"","methodology":"Researchers designed chimeric quinolone derivatives by attaching amphiphilic peptide-mimicking moieties to ciprofloxacin. They tested antimicrobial activity against panels of multidrug-resistant bacteria using standard susceptibility tests, assessed hemolytic toxicity, and measured resistance development rates compared to ciprofloxacin. Molecular dynamics simulations modeled membrane interactions. In vivo efficacy was tested in a mouse MRSA skin infection model with single-dose treatment.","limitations":"The in vivo testing was limited to a single mouse MRSA skin infection model. Systemic infections, different bacterial species, and deeper tissue infections were not tested. Long-term resistance development in serial passage experiments wasn't detailed beyond comparison to ciprofloxacin. Pharmacokinetics, bioavailability, and tissue distribution data were not described in the abstract. The compound would need extensive safety and efficacy testing before clinical trials."},{"rthcId":"RPEP-14129","title":"The effects of non-insulin anti-diabetic medications on the diabetic microvascular complications: a systematic review and meta-analysis of randomized clinical trials.","authors":"Wen, Song; Yuan, Yue; Li, Yanyan; Xu, Chenglin; Chen, Lijiao; Ren, Yishu; Wang, Congcong; He, Yanju; Li, Xiucai; Gong, Min; Yuan, Xinlu; Xu, Dongxiang; Wang, Chaoxun; Zhou, Ligang","year":2025,"journal":"BMC endocrine disorders, 25(1), 179","doi":"10.1186/s12902-025-01985-2","pmid":"40665260","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14130","title":"The novel antidiabetic medications on diabetic retinopathy: relevant molecular mechanisms, advancing diagnostic innovations, and therapeutic implications.","authors":"Wen, Song; Xu, Chenglin; Yuan, Yue; Chen, Lijiao; Ren, Yishu; Xu, Zhimin; Jin, Jianlan; Li, Jiyu; Zhou, Ligang","year":2025,"journal":"Frontiers in medicine, 12, 1670643","doi":"10.3389/fmed.2025.1670643","pmid":"41608415","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Novel antidiabetic medications including GLP-1 receptor agonists, SGLT-2 inhibitors, and dual GIP/GLP-1 agonists target the key molecular pathways underlying early diabetic retinopathy: microvascular damage, inflammation, oxidative stress, and advanced glycation end products. These drugs may have the potential to reduce progression of non-proliferative diabetic retinopathy (NPDR), though clinical trial confirmation is expected.\n\nThe review also highlights that advanced diagnostic technologies — ultra-widefield fundus photography, OCT, OCTA, and AI-based algorithms — achieve over 95% accuracy in detecting NPDR and can predict systemic cardiovascular risk from retinal imaging.","whyItMatters":"Diabetic retinopathy affects a significant proportion of the world's 500+ million people with diabetes. Current eye treatments (laser, injections) address late-stage disease. If drugs patients are already taking for blood sugar control also protect their eyes at the molecular level, it could prevent millions of cases of vision loss without any additional treatment — a paradigm shift from reactive to preventive eye care in diabetes.","specificNumbers":"","methodology":"Narrative review of molecular mechanisms underlying diabetic retinopathy, the pharmacological profiles of novel antidiabetic drugs and their potential retinal effects, and advances in diagnostic imaging and AI-based detection algorithms.","limitations":"This is a narrative review, not a systematic review or meta-analysis. Much of the evidence for retinal protective effects of GLP-1 agonists comes from preclinical studies and secondary analyses of cardiovascular outcome trials rather than dedicated retinopathy endpoint trials. The potential benefits are described as expected rather than proven. Early concerns about semaglutide and retinopathy progression in certain trials are not clearly addressed."},{"rthcId":"RPEP-14131","title":"Decreases in circulating ANGPTL3/8 concentrations following retatrutide treatment parallel reductions in serum lipids.","authors":"Wen, Yi; Lemen, Deven; Lin, Yanzhu; Chen, Yan Q; Regmi, Ajit; Roell, William C; Thomas, Melissa K; Hartman, Mark L; Coskun, Tamer; Milicevic, Zvonko; Haupt, Axel; Ruotolo, Giacomo; Konrad, Robert J","year":2025,"journal":"Diabetes, obesity & metabolism, 27(10), 5985-5995","doi":"10.1111/dom.16661","pmid":"40726454","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14132","title":"Aurantii fructus immaturus (Rutaceae) flavonoid ameliorated constipation by regulating colonic microbiota and miRNA/mRNA network.","authors":"Wen, Yong; Zhan, Yu; Du, Li-Juan; Li, Jun; Shen, Xu-Long; He, Bin; Chen, Tai-Yu; Tang, Xue-Gui","year":2025,"journal":"Journal of traditional and complementary medicine, 15(5), 559-572","doi":"10.1016/j.jtcme.2024.11.011","pmid":"40979483","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14133","title":"Mechanical Reinforced and Self-healing Hydrogels: Bioprinted Biomimetic Methacrylated Collagen Peptide-Xanthan Gum Constructs for Ligament Regeneration.","authors":"Weng, Hongjuan; Decarli, Monize Caiado; He, Lei; Chen, Wen; van Rijt, Sabine; Bernaerts, Katrien V; Moroni, Lorenzo","year":2025,"journal":"Advanced healthcare materials, 14(25), e2502341","doi":"10.1002/adhm.202502341","pmid":"40665850","tags":[],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Researchers developed a 3D-bioprinted hydrogel scaffold using methacrylated collagen peptide combined with xanthan gum (COPMA-XG) that overcomes the traditional limitations of collagen peptides in tissue engineering — namely low viscosity and poor printability. The resulting bioinks showed self-healing properties, rapid UV-curing, tunable mechanical strength, and stable structure in culture medium.\n\nWhen loaded with human bone marrow stem cells (hMSCs) and cultured for 28 days, the bioprinted constructs were biocompatible and promoted stem cell proliferation and differentiation into ligament-like tissue, with increased production of extracellular matrix, collagen type I, and scleraxis (a ligament-specific marker).","whyItMatters":"Ligament injuries are common and heal poorly due to limited blood supply. Current surgical options often use grafts that have drawbacks. Collagen peptides are promising for tissue regeneration because they're water-soluble and bioactive, but they've been difficult to 3D-print into stable structures. This study solves that problem by combining collagen peptides with xanthan gum, creating a printable, self-healing scaffold that actually directs stem cells toward ligament tissue formation. This could eventually enable custom-printed ligament replacements.","specificNumbers":"28-day culture period · hMSCs differentiation confirmed · Increased collagen type I production · Increased scleraxis expression · Self-healing hydrogels · UV-curable","methodology":"The researchers first synthesized methacrylated collagen peptide (COPMA) hydrogels with UV-curing capability and tunable mechanical properties. They then mixed COPMA with xanthan gum (XG) at various ratios to create bioinks with improved printability and mechanical strength. The COPMA-XG bioinks were used to 3D-bioprint constructs containing human bone marrow mesenchymal stem cells. The constructs were evaluated for self-healing, printability, structural stability, biocompatibility, and stem cell differentiation toward ligament lineage over 28 days.","limitations":"This is an in vitro study — the bioprinted constructs have not been tested in animal models or humans. Long-term mechanical durability under physiological loading conditions (as experienced in a real ligament) was not assessed. The transition from lab-scale bioprinting to clinically relevant construct sizes and implantation remains a significant challenge."},{"rthcId":"RPEP-14134","title":"Glucagon-Like Peptide-1 Receptor Agonist Therapy Does Not Increase Gastrointestinal Adverse Events in Patients with Inflammatory Bowel Disease.","authors":"Weng, Jonathan; Alizadeh, Madeline; Friedman, Sonia","year":2025,"journal":"Digestive diseases and sciences, 70(10), 3476-3484","doi":"10.1007/s10620-025-09344-w","pmid":"40830314","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14135","title":"Gut Hormones and Inflammatory Bowel Disease.","authors":"Weng, Jonathan; Lo, Chunmin C","year":2025,"journal":"Biomolecules, 15(7)","doi":"10.3390/biom15071013","pmid":"40723884","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14136","title":"Higher socioeconomic status is associated with dispensation of monoclonal antibodies against calcitonin gene-related peptide in migraine: A nested case-control study.","authors":"Wennersten, Therese; Lindh, Jonatan D; Nilsson Remahl, A Ingela M; Andersson, Marine L; von Euler, Mia; Wirdefeldt, Karin; Ekheden, Isabella","year":2025,"journal":"Cephalalgia : an international journal of headache, 45(6), 3331024251348648","doi":"10.1177/03331024251348648","pmid":"40528434","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14137","title":"Alterations in one-carbon metabolism in metabolic dysfunction associated steatotic liver disease may be modified by semaglutide.","authors":"Werge, Mikkel Parsberg; McCann, Adrian; Rashu, Elias Badal; Lam, Shi Min; Hetland, Liv Eline; Thing, Mira; Nabilou, Puria; Junker, Anders Ellekaer; Norlin, Jenny; Veidal, Sanne; Holst, Dorte; Bugge, Anne; Viuff, Birgitte Martine; Hvid, Henning; Bendtsen, Kristian M; Mazzoni, Gianluca; Harder, Lea Moerch; Vyberg, Mogens; Serizawa, Reza; Bendtsen, Flemming; Ueland, Per Magne; Galsgaard, Elisabeth Douglas; Wewer Albrechtsen, Nicolai J; Gluud, Lise Lotte","year":2025,"journal":"Annals of hepatology, 30(2), 102107","doi":"10.1016/j.aohep.2025.102107","pmid":"40889707","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14138","title":"Are Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists Central Nervous System (CNS) Penetrant: A Narrative Review.","authors":"West, Juliana; Li, Maggie; Wong, Sabrina; Le, Gia Han; Teopiz, Kayla M; Valentino, Kyle; Dri, Christine E; McIntyre, Roger S","year":2025,"journal":"Neurology and therapy, 14(4), 1157-1166","doi":"10.1007/s40120-025-00724-y","pmid":"40172827","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14139","title":"Weight Gain Was Associated With Worsening Glycemia and Cardiovascular and Kidney Outcomes in Patients With Type 2 Diabetes Independent of Diabetes Medication in the GRADE Randomized Controlled Trial.","authors":"Wexler, Deborah J; Garvey, W Timothy; Ghosh, Alokananda; Kazemi, Erin J; Krause-Steinrauf, Heidi; Ahmann, Andrew J; Brown-Friday, Janet; Casula, Sabina; Cherrington, Andrea L; Elasy, Tom A; Fortmann, Stephen P; Krakoff, Jonathan A; Mudaliar, Sunder; Tiktin, Margaret; Younes, Naji","year":2025,"journal":"Diabetes care, 48(6), 935-944","doi":"10.2337/dc24-2825","pmid":"40267365","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 4,980 participants followed for 5 years (mean age 57, BMI 34.3, HbA1c 7.5%):\n\nFirst-year weight changes:\n• Liraglutide: -3.5 kg (95% CI: -3.8 to -3.2)\n• Sitagliptin: -1.07 kg (-1.4 to -0.78)\n• Insulin glargine: +0.45 kg (+0.16 to +0.74)\n• Glimepiride: +0.89 kg (+0.60 to +1.2)\n• All groups P significant for differences\n\nWeight gain consequences (per kg, independent of drug):\n• HbA1c >7.5%: HR 1.05 (95% CI: 1.04-1.07)\n• Cardiovascular disease: HR 1.03 (1.005-1.06)\n• Kidney disease: HR 1.03 (1.01-1.06)\n• Lower diabetes treatment satisfaction\n• Baseline weight (not weight gain) predicted new-onset neuropathy","whyItMatters":"This is landmark evidence from one of the largest head-to-head diabetes drug trials ever conducted. It demonstrates two things: first, that liraglutide (a GLP-1 peptide) produces significantly more weight loss than three other major diabetes drug classes. Second, that weight gain — regardless of drug — independently worsens the very complications diabetes drugs are meant to prevent. This fundamentally supports prioritizing weight-reducing medications like GLP-1 agonists in diabetes management.","specificNumbers":"","methodology":"The GRADE study was a large, multicenter, randomized controlled trial comparing four diabetes medications added to metformin in patients with type 2 diabetes. 4,980 participants were followed for up to 5 years. Weight was measured over the study period, and hazard ratios were calculated per kilogram of weight change for glycemic, cardiovascular, kidney, neuropathy, and treatment satisfaction outcomes.","limitations":"Weight change was not a pre-specified primary outcome of the GRADE trial. The analysis is observational within a randomized framework — while treatment assignment was randomized, the weight change-outcome associations are adjusted but not randomized. Liraglutide doses in GRADE may differ from those used in current obesity practice. The study population (BMI 34.3, early diabetes) may not represent all type 2 diabetes patients. Neuropathy was not associated with weight gain, suggesting the relationship is not universal across complications."},{"rthcId":"RPEP-14140","title":"Once-weekly semaglutide 7·2 mg in adults with obesity (STEP UP): a randomised, controlled, phase 3b trial.","authors":"Wharton, Sean; Freitas, Paula; Hjelmesæth, Jøran; Kabisch, Maria; Kandler, Kristian; Lingvay, Ildiko; Quiroga, Maria; Rosenstock, Julio; Garvey, W Timothy","year":2025,"journal":"The lancet. Diabetes & endocrinology, 13(11), 949-963","doi":"10.1016/S2213-8587(25)00226-8","pmid":"40961952","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14141","title":"Oral Semaglutide at a Dose of 25 mg in Adults with Overweight or Obesity.","authors":"Wharton, Sean; Lingvay, Ildiko; Bogdanski, Pawel; Duque do Vale, Ruben; Jacob, Stephan; Karlsson, Tobias; Shaji, Chaithra; Rubino, Domenica; Garvey, W Timothy","year":2025,"journal":"The New England journal of medicine, 393(11), 1077-1087","doi":"10.1056/NEJMoa2500969","pmid":"40934115","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"At 64 weeks, oral semaglutide 25 mg produced a mean body weight reduction of 13.6% versus 2.2% for placebo (estimated difference: -11.4 percentage points; 95% CI: -13.9 to -9.0; P < 0.001). Participants on semaglutide were significantly more likely to achieve weight loss thresholds of 5%, 10%, 15%, and 20% or more (P < 0.001 for all comparisons).\n\nPhysical function quality of life (IWQOL-Lite-CT score) also improved significantly with oral semaglutide versus placebo (P < 0.001). Gastrointestinal adverse events were the most common side effects, occurring in 74.0% of semaglutide patients versus 42.2% of placebo patients.","whyItMatters":"Injectable semaglutide (Wegovy) is already a blockbuster weight loss drug, but many patients prefer pills to injections. This trial shows a 25 mg oral dose — lower than the 50 mg also being studied — can produce clinically significant weight loss of nearly 14%. This dose could offer a middle ground: more weight loss than the current 14 mg oral dose (approved for diabetes as Rybelsus) while being more practical than injections for patients who prefer oral medication.","specificNumbers":"","methodology":"OASIS 4 was a 71-week, double-blind, randomized, placebo-controlled trial conducted at 22 sites across four countries. 307 participants without diabetes who had a BMI ≥30 (or ≥27 with at least one obesity-related complication) were randomized 2:1 to oral semaglutide 25 mg or placebo once daily, alongside lifestyle interventions. Coprimary endpoints at week 64 were percent change in body weight and achieving ≥5% weight loss.","limitations":"The sample size (307 participants) is modest for a phase 3 weight loss trial. People with diabetes were excluded, limiting generalizability. The 74% gastrointestinal adverse event rate is high, though described as predominantly transient. The trial was funded by Novo Nordisk, the manufacturer. No head-to-head comparison with injectable semaglutide was performed in this trial."},{"rthcId":"RPEP-14142","title":"Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment.","authors":"Wharton, Sean; Aronne, Louis J; Stefanski, Adam; Alfaris, Nasreen F; Ciudin, Andreea; Yokote, Koutaro; Halpern, Bruno; Shukla, Alpana P; Zhou, Chunmei; Macpherson, Lisa; Allen, Sheryl E; Ahmad, Nadia N; Klise, Suzanne R","year":2025,"journal":"The New England journal of medicine, 393(18), 1796-1806","doi":"10.1056/NEJMoa2511774","pmid":"40960239","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14143","title":"Treatment with orforglipron, an oral glucagon like peptide-1 receptor agonist, is associated with improvements of CV risk biomarkers in participants with type 2 diabetes or obesity without diabetes.","authors":"Wharton, Sean; Rosenstock, Julio; Konige, Manige; Lin, Yanzhu; Duffin, Kevin; Wilson, Jonathan; Banerjee, Hiya; Pirro, Valentina; Kazda, Christof; Mather, Kieren","year":2025,"journal":"Cardiovascular diabetology, 24(1), 240","doi":"10.1186/s12933-025-02781-x","pmid":"40481478","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Orforglipron produced significant placebo-adjusted decreases in blood pressure, LDL cholesterol, triglycerides, ApoB, ApoC3, and hsCRP in both the T2D study (N=361, 26 weeks) and the obesity study (N=234, 36 weeks). Improvements in CV risk markers at 12 mg were of similar magnitude to those seen at 24, 36, and 45 mg doses, suggesting a plateau effect for cardiovascular benefits. The improvements were consistent across both populations — people with type 2 diabetes and people with obesity alone — indicating the cardiovascular benefits are not limited to diabetic patients.","whyItMatters":"Current GLP-1 drugs like semaglutide require injections, which many patients avoid. Orforglipron as a daily pill could dramatically expand access to GLP-1 therapy. Showing cardiovascular risk reduction — on top of weight loss and blood sugar control — strengthens the case for orforglipron as a comprehensive cardiometabolic treatment.","specificNumbers":"","methodology":"Exploratory analysis of cardiovascular risk biomarkers from two phase 2 randomized controlled trials. The T2D study (NCT05048719) randomized 361 participants (mean age 59, mean BMI 35.3, mean HbA1c 8.1%) to orforglipron 3-45 mg daily, dulaglutide 1.5 mg weekly, or placebo for 26 weeks. The obesity study (NCT05051579) randomized 234 participants (mean age 54, mean BMI 37.9) to orforglipron 12-45 mg daily or placebo for 36 weeks. Blood pressure, lipids, ApoB, ApoC3, NT-pro-BNP, hsCRP, and IL-6 were measured at baseline and endpoint.","limitations":"This was an exploratory post-hoc analysis of phase 2 trial data, not a dedicated cardiovascular outcome trial. The studies were not powered to detect differences in actual cardiovascular events like heart attacks or strokes. Follow-up was relatively short (26-36 weeks). Specific numeric improvements for each biomarker were not detailed in the abstract. Phase 3 cardiovascular outcome trials are needed to confirm clinical benefit."},{"rthcId":"RPEP-14144","title":"Patient Preferences for Episodic Migraine Medications: A Discrete Choice Experiment of Self-Injectable Versus Oral Treatments Targeting Calcitonin Gene-Related Peptide Pathway.","authors":"Whichello, Chiara; Viktrup, Lars; Varnado, Oralee J; Quaife, Matthew; Trapali, Myrto; Tockhorn-Heidenreich, Antje","year":2025,"journal":"Patient preference and adherence, 19, 839-853","doi":"10.2147/PPA.S496736","pmid":"40177623","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14145","title":"Formulation and characterization of exenatide-loaded PLGA microspheres prepared by coacervation.","authors":"White, Cameron; Schwendeman, Steven P","year":2025,"journal":"Drug delivery and translational research","doi":"10.1007/s13346-025-02008-2","pmid":"41364402","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14146","title":"Preoperative GLP-1 Receptor Agonist Use and Postoperative Outcomes Following Operative Ankle Fracture Repair in Patients With Type 2 Diabetes: A National Database Study.","authors":"White, Carter J K; Choudhury, Ankit; Bollepalli, Harshavardhan; Kodra, Jacob D; Burton, Alex T; Kraus, Jonathan C","year":2025,"journal":"Foot & ankle international, 46(11), 1265-1274","doi":"10.1177/10711007251364187","pmid":"40923457","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14147","title":"Concerning BPC-157, a natural pentadecapeptide, that acts as a cytoprotectant and is believed to protect the gastro-intestinal tract (GIT).","authors":"Whitehouse, Michael","year":2025,"journal":"Inflammopharmacology, 33(8), 4879-4881","doi":"10.1007/s10787-025-01882-z","pmid":"40759852","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14148","title":"Prescribing Patterns and Adverse Effects of Semaglutide: A Real-World Comparative Evaluation.","authors":"Whorton, Abigail; Osman, Samira; Johal, Jaspal; Baig, Sarah; Jones, Alan M; Jalal, Zahraa","year":2025,"journal":"Healthcare (Basel, Switzerland), 14(1)","doi":"10.3390/healthcare14010035","pmid":"41516966","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14149","title":"Endothelial senescence drives intrinsic skin aging via the neuroimmune CGRP-mast cell axis in mice.","authors":"Wicaksono, Satrio Adi; Ryanto, Gusty Rizky Teguh; Suzuki, Yoko; Hara, Tetsuya; Ikeda, Koji; Fukumoto, Takeshi; Hirata, Ken-Ichi; Otake, Hiromasa; Emoto, Noriaki","year":2025,"journal":"Communications biology, 8(1), 1696","doi":"10.1038/s42003-025-09097-2","pmid":"41299075","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Using an endothelial cell-specific senescent mouse model, researchers identified a novel neuroimmune pathway driving intrinsic skin aging. Senescent endothelial cells secrete pro-inflammatory SASP factors that activate dermal neurons to produce calcitonin gene-related peptide (CGRP). This CGRP triggers mast cell degranulation through a non-IgE-mediated pathway, leading to dermal thinning, collagen degradation, and delayed wound healing. Pharmacological stabilization of mast cells or inhibition of the EC-SASP-CGRP pathway significantly attenuated all three hallmarks of intrinsic skin aging.","whyItMatters":"This study reveals that skin aging isn't just about what happens in skin cells — it starts with aging blood vessels that set off a chain reaction involving nerves, peptides, and immune cells. This opens up entirely new therapeutic targets: instead of treating skin aging at the surface, interventions could target the underlying CGRP-mast cell axis to prevent or reverse aging from within.","specificNumbers":"","methodology":"The researchers created an endothelial cell-specific senescent mouse model to study vascular contributions to skin aging. They tracked the cascade from senescent endothelial cells through neuronal activation to mast cell degranulation. They used pharmacological interventions to stabilize mast cells and inhibit the CGRP pathway, measuring outcomes of dermal thickness, collagen integrity, and wound healing capacity.","limitations":"This study was conducted entirely in mice, and results may not directly translate to human skin aging. The mouse model used engineered endothelial cell senescence, which may not fully replicate natural aging processes. The study focused on intrinsic (age-related) skin aging and did not address extrinsic factors like UV exposure. Long-term effects of blocking the CGRP pathway on skin health are unknown."},{"rthcId":"RPEP-14150","title":"Integrative gene-metabolite network analysis of GLP-1 receptor agonists and related incretin pathways in cardiometabolic health.","authors":"Wicik, Zofia; Nowak-Szwed, Anna; Eyileten, Ceren; Sourij, Harald; von Lewinski, Dirk; Kistkins, Svjatoslavs; Borkowska, Joanna; Postuła, Marek","year":2025,"journal":"NPJ systems biology and applications, 11(1), 144","doi":"10.1038/s41540-025-00619-6","pmid":"41274923","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14151","title":"Elevated plasma levels of calcitonin gene-related peptide in individuals with rosacea: A cross-sectional case-control study.","authors":"Wienholtz, Nita K F; Christensen, Casper E; Ashina, Håkan; Jørgensen, Niklas R; Egeberg, Alexander; Thyssen, Jacob P; Ashina, Messoud","year":2025,"journal":"Journal of the European Academy of Dermatology and Venereology : JEADV, 39(1), 181-188","doi":"10.1111/jdv.19954","pmid":"38558478","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14152","title":"Frailty in randomized controlled trials of glucose-lowering therapies for type 2 diabetes: An individual participant data meta-analysis of frailty prevalence, treatment efficacy, and adverse events.","authors":"Wightman, Heather; Butterly, Elaine; Wei, Lili; McChrystal, Ryan; Sattar, Naveed; Adler, Amanda; Phillippo, David; Dias, Sofia; Welton, Nicky; Clegg, Andrew; Witham, Miles; Rockwood, Kenneth; McAllister, David A; Hanlon, Peter","year":2025,"journal":"PLoS medicine, 22(4), e1004553","doi":"10.1371/journal.pmed.1004553","pmid":"40193407","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14153","title":"Changes in gastrointestinal motility and gut hormone secretion after Roux-en-Y gastric bypass and sleeve gastrectomy for individuals with severe obesity.","authors":"Wilbrink, Jennifer A; van Avesaat, Mark; Nienhuijs, Simon W; Stronkhorst, Arnold; Masclee, Ad A M","year":2025,"journal":"Clinical obesity, 15(2), e12721","doi":"10.1111/cob.12721","pmid":"39727180","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Both Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) produced significant weight loss and dramatically increased postprandial secretion of the distal gut peptides GLP-1 and PYY — hormones involved in satiety and blood sugar regulation. Gastric emptying was significantly accelerated after both procedures.\n\nA notable difference emerged: oro-cecal transit time (how fast food travels from mouth to large intestine) was significantly accelerated after SG but not after RYGB. Despite the parallel increases in peptide release and faster motility, no significant correlations were found between changes in gut peptide levels, changes in GI motility, and clinical outcomes like weight loss.","whyItMatters":"Understanding how bariatric surgery reshapes gut peptide signaling helps explain why these procedures work beyond simple stomach restriction. The surge in GLP-1 and PYY after surgery mirrors the mechanism of popular weight-loss drugs like semaglutide, suggesting the gut hormone response is central to sustained weight management. The differences between the two surgeries in transit time and peptide patterns could eventually help clinicians match patients with the procedure most likely to benefit them.","specificNumbers":"","methodology":"This was a prospective single-center study following 28 severely obese individuals before surgery and at 2 and 12 months after either RYGB or SG. At each time point, participants ate a standardized 459 kcal solid meal, and blood samples were taken to measure GLP-1, PYY, ghrelin, insulin, and glucose. Gastric emptying was assessed with a 13C octanoic acid breath test, and oro-cecal transit time was measured via lactulose hydrogen breath testing. Satiation was tracked using visual analog scale (VAS) scores.","limitations":"The sample size of 28 patients is relatively small, which limits statistical power to detect correlations between peptide changes and clinical outcomes. The study was conducted at a single center, which may limit generalizability. The follow-up period of 12 months, while informative, does not capture longer-term hormonal adaptation that may occur years after surgery. The 459 kcal standardized meal may not reflect typical post-surgical eating patterns."},{"rthcId":"RPEP-14154","title":"Smoldering inflammation: The silent flame driving heart failure.","authors":"Wilk, Michał Maksymilian; Wilk, Jakub; Florek, Kamila; Zimoch, Wojciech Jan","year":2025,"journal":"Dental and medical problems, 62(5), 963-976","doi":"10.17219/dmp/210102","pmid":"41186161","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14155","title":"Cardiorenal outcomes of weight loss interventions in people with CKD and type 2 diabetes.","authors":"Wilkinson, Thomas J; Goldney, Jonathan; Yates, Thomas; Henson, Joseph; Zaccardi, Francesco; Khunti, Kamlesh; Webb, David; Papamargaritis, Dimitris; Davies, Melanie J","year":2025,"journal":"Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association","doi":"10.1093/ndt/gfaf258","pmid":"41344888","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14156","title":"Data-Independent Immunopeptidomics Discovery of Low-Abundant Bacterial Epitopes.","authors":"Willems, Patrick; Staes, An; Miret-Casals, Laia; Demichev, Vadim; Devos, Simon; Impens, Francis","year":2025,"journal":"Journal of proteome research, 24(12), 6295-6304","doi":"10.1021/acs.jproteome.5c00449","pmid":"41166551","tags":["peptide-vaccines","immunopeptidomics","mass-spectrometry"],"studyType":"methods","evidenceStrength":"preliminary","keyFinding":"A new data-independent acquisition (DIA) mass spectrometry approach dramatically improved the detection of rare bacterial peptides displayed on immune cells. Using Listeria monocytogenes as a model pathogen, researchers showed that DIA workflows found additional human and bacterial immunopeptides missed by the standard data-dependent (DDA) method. Their most powerful approach used DIA-NN software to generate and search predicted peptide libraries covering approximately 150 million immunopeptide precursors, outperforming all other methods at identifying MHC class I peptides — the molecular targets that guide vaccine and immunotherapy design.","whyItMatters":"Finding the right peptide targets is the critical first step in designing vaccines and immunotherapies. Many important bacterial peptides are present in very low amounts on cell surfaces, making them invisible to standard detection methods. This improved approach can identify these rare peptide targets, potentially accelerating the development of vaccines against intracellular pathogens and expanding the pool of targets available for cancer immunotherapy.","specificNumbers":"~150 million immunopeptide precursors scored · DIA outperformed DDA for low-abundant peptides · Listeria monocytogenes model pathogen","methodology":"Researchers compared two mass spectrometry approaches — data-independent acquisition (diaPASEF) versus conventional data-dependent acquisition (ddaPASEF) — for profiling immunopeptides from cells infected with Listeria monocytogenes. They tested DIA spectrum-centric workflows and also used DIA-NN software to generate proteome-wide predicted HLA class I peptide spectral libraries, scoring approximately 150 million peptide precursors to identify both abundant and rare immunopeptides.","limitations":"This is a methods development study using a single model pathogen (Listeria monocytogenes). The approach needs validation across other pathogens and in clinical settings. The computational demands of searching 150 million precursors may limit accessibility. Peptide identification does not guarantee immunogenicity — the peptides still need biological validation to confirm they trigger immune responses."},{"rthcId":"RPEP-14157","title":"Intrarectal Antagonism of Calcitonin Gene-Related Peptide Prevents Spinal Cord Injury-Associated Neurogenic Bowel Phenotypes.","authors":"Willits, Adam B; Kader, Leena; Choudhury, Sonali; Ewald, Morgan; Meriano, Sebastian; Christianson, Julie; Baumbauer, Kyle; Young, Erin","year":2025,"journal":"Journal of neurotrauma","doi":"10.1177/08977151251406659","pmid":"41467995","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14158","title":"Development of a cell-penetrating peptide-based nanocomplex for long-term delivery of intact mitochondrial DNA into epithelial cells.","authors":"Wilson, Kyrie; Holjencin, Charles; Lee, Hwaran; Annamalai, Balasubramaniam; Ishii, Masaaki; Gilbert, Jeremy L; Jakymiw, Andrew; Rohrer, Bärbel","year":2025,"journal":"Molecular therapy. Nucleic acids, 36(1), 102449","doi":"10.1016/j.omtn.2025.102449","pmid":"39991470","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14159","title":"Semaglutide, tirzepatide, and retatrutide attenuate the interoceptive effects of alcohol in male and female rats.","authors":"Windram, McKinley; Lovelock, Dennis F; Carew, Joseph M; Krieman, Caroline G; Hendershot, Christian S; Besheer, Joyce","year":2025,"journal":"Psychopharmacology","doi":"10.1007/s00213-025-06854-3","pmid":"40699363","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14160","title":"First-in-human intranasal [13N]oxytocin PET: evaluation of feasibility, biodistribution, and radiation dosimetry.","authors":"Winterdahl, Michael; Nielsen, Erik Nguyen; Hansen, Søren B; Dias, André Henrique; Vendelbo, Mikkel Holm; Jakobsen, Steen; Yeomans, David","year":2025,"journal":"EJNMMI research, 15(1), 137","doi":"10.1186/s13550-025-01329-0","pmid":"41251983","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In six healthy volunteers who received intranasal [13N]oxytocin, PET/MRI scans showed high tracer uptake in the nasal cavity within the first 5 minutes, followed by decline and systemic absorption. Tracer was detectable in brain regions between 25-45 minutes post-administration, but uptake was low and variable between individuals.\n\nTracer uptake in the trigeminal ganglia and brain showed no clear dose-dependency. One participant with rhinitis showed altered uptake and clearance patterns, suggesting nasal health affects delivery. The nasal cavity was identified as the dose-limiting organ for radiation safety. The researchers concluded that [13N]oxytocin via intranasal administration is not well suited for central nervous system receptor imaging at this stage.","whyItMatters":"Intranasal delivery is widely promoted as a way to get peptides past the blood-brain barrier and into the brain. However, until this study, there was limited direct evidence showing where intranasal oxytocin actually goes in humans. The finding that brain uptake is low and variable challenges assumptions underlying many oxytocin nasal spray studies and highlights the need for better delivery methods.","specificNumbers":"","methodology":"Six healthy volunteers received intranasal [13N]oxytocin (a radioactively labeled version of oxytocin) and underwent whole-body or head PET/MRI scans. Researchers tracked the peptide's distribution over time using time-activity curves, evaluated uptake in the nasal cavity, trigeminal ganglia, and brain regions, and performed radiation dosimetry analysis. The study was registered on ClinicalTrials.gov (NCT06954650).","limitations":"The sample size of six participants is very small, limiting generalizability. The short half-life of the 13N radiotracer (approximately 10 minutes) restricted the imaging window and complicated brain uptake assessment. High nasal cavity radioactivity created spillover effects that made precise brain region quantification difficult. Image co-registration between PET and MRI was challenged by these technical limitations. The study only assessed healthy volunteers, not patients with neuropsychiatric conditions."},{"rthcId":"RPEP-14161","title":"Epicardial Adipose Tissue-A Novel Therapeutic Target in Obesity Cardiomyopathy.","authors":"Wiszniewski, Kacper; Grudniewska, Anna; Szabłowska-Gadomska, Ilona; Pilichowska-Paszkiet, Ewa; Zaborska, Beata; Zgliczyński, Wojciech; Dudek, Piotr; Bik, Wojciech; Sota, Marcin; Mrozikiewicz-Rakowska, Beata","year":2025,"journal":"International journal of molecular sciences, 26(16)","doi":"10.3390/ijms26167963","pmid":"40869284","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14162","title":"Gastrointestinal Symptoms in Obesity Therapy: Mechanisms, Epidemiology, and Management Strategies.","authors":"Witaszek, Tomasz; Biesiada, Aleksander; Iskra-Trifunović, Joanna; Babicki, Mateusz; Mastalerz-Migas, Agnieszka; Kłoda, Karolina","year":2025,"journal":"Biomedicines, 13(10)","doi":"10.3390/biomedicines13102362","pmid":"41153649","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Gastrointestinal adverse effects occur in 65–84% of patients treated with incretin-based anti-obesity medications (liraglutide, semaglutide, tirzepatide), with nausea and diarrhea being the most common. These symptoms are primarily caused by altered gastric motility and hormone-mediated changes in appetite signaling. Preventive strategies including slow dose titration, dietary counseling, and supportive medications can improve tolerability and treatment continuation.","whyItMatters":"GLP-1 receptor agonists and dual GLP-1/GIP agonists are transforming obesity treatment, but their high rates of GI side effects are a major barrier to adherence. Up to 84% of patients experience these symptoms, and many discontinue treatment as a result. Understanding the mechanisms and management of these side effects is critical for clinicians to maximize the long-term success of these peptide-based therapies.","specificNumbers":"65–84% GI adverse event rate · Liraglutide, semaglutide, tirzepatide · Most common: nausea, diarrhea · Also: constipation, GERD, cholelithiasis · 2006–2025 literature review","methodology":"Literature review searching PubMed and Scopus for articles published 2006–2025. Included randomized controlled trials, observational studies, and narrative/systematic reviews reporting GI adverse effects in obesity treatments, with focus on incretin-based anti-obesity medications.","limitations":"As a narrative review, it synthesizes existing evidence without meta-analytic pooling. GI symptom reporting varies across trials, making direct comparisons difficult. The review focuses on published trial data, which may underrepresent real-world GI side effect severity and impact on quality of life. Management strategies discussed are largely based on clinical experience and guidelines rather than randomized evidence."},{"rthcId":"RPEP-14163","title":"Blood Biomarkers as a Non-Invasive Method for the Assessment of the State of the Fontan Circulation.","authors":"Wittczak, Andrzej; Mazurek-Kula, Anna; Banach, Maciej; Piotrowski, Grzegorz; Bielecka-Dabrowa, Agata","year":2025,"journal":"Journal of clinical medicine, 14(2)","doi":"10.3390/jcm14020496","pmid":"39860501","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14164","title":"Is Carvedilol Effective in Preventing and Modulating Concentric Cardiac Remodelling? A Comprehensive Systematic Review and Meta-Analyses.","authors":"Wiyono, Alice Valeria; Ardinal, Azizah Puspitasari","year":2025,"journal":"Cardiovascular therapeutics, 2025, 9108324","doi":"10.1155/cdr/9108324","pmid":"41194854","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14165","title":"Modulating Matrix Metalloproteinase Activity in Obesity: Comparative Effects of Bariatric Surgery and GLP-1/GIP-Based Pharmacotherapy.","authors":"Wiśniewski, Konrad; Choromańska, Barbara; Maciejczyk, Mateusz; Dadan, Jacek; Myśliwiec, Piotr","year":2025,"journal":"Journal of clinical medicine, 14(21)","doi":"10.3390/jcm14217648","pmid":"41227041","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Bariatric surgery consistently reduces MMP-9 levels and normalizes MMP-2 activity in obese patients, contributing to improved extracellular matrix integrity, reduced inflammation, and enhanced insulin sensitivity. These changes reflect a correction of the tissue-remodeling dysfunction characteristic of obesity.\n\nGLP-1 receptor agonists and dual GLP-1/GIP agonists achieve substantial weight loss and glycemic control, but current evidence regarding their direct effects on MMP activity remains limited. This gap suggests that the tissue-level effects of pharmacotherapy may not fully replicate those of surgery, despite comparable weight loss outcomes.","whyItMatters":"This review highlights an underappreciated dimension of obesity treatment: beyond weight loss and blood sugar, the body's tissue-remodeling machinery needs to recover. If GLP-1 drugs don't fully correct MMP dysregulation the way surgery does, patients might still carry risk for obesity-related tissue damage even after losing weight pharmacologically. This could influence how we evaluate and compare obesity treatments.","specificNumbers":"","methodology":"Narrative review analyzing literature from PubMed, Scopus, and Web of Science (2015-2024). The authors focused on studies evaluating MMPs, inflammation markers, and metabolic parameters in the context of bariatric surgery and GLP-1/GIP-based pharmacotherapy for obesity.","limitations":"This is a narrative review, not a systematic review or meta-analysis, which may introduce selection bias in the literature covered. The limited evidence on GLP-1/GIP effects on MMPs makes direct comparison with surgery difficult. MMP measurements vary across studies in terms of assay methods and tissue sources. The review does not distinguish between different types of bariatric surgery."},{"rthcId":"RPEP-14166","title":"Increased cathelicidin LL-37 colonic expression is associated with tumor progression in colorectal cancer.","authors":"Wlodarczyk, J; Dziki, L; Fichna, J","year":2025,"journal":"Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 76(6), 707-715","doi":"10.26402/jpp.2025.6.08","pmid":"41569060","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14167","title":"Success of 177Lu-DOTATATE therapy in a metastatic pituitary neuroendocrine tumor.","authors":"Wolf, Katherine I; Lu, Zhonglin; Hesseltine, Elizabeth A; Wong, Ka-Kit; Worden, Francis P; Else, Tobias","year":2025,"journal":"Endocrine oncology (Bristol, England), 5(1), e250073","doi":"10.1530/EO-25-0073","pmid":"41126982","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A 55-year-old male with an ACTH-secreting pituitary neuroendocrine tumor (PitNET) underwent over a decade of treatments:\n- Recurrent transsphenoidal resections (multiple surgeries)\n- Gamma knife irradiation\n- Somatostatin analog therapy\n- Steroidogenesis inhibitors\n\nNone achieved lasting control. Metastatic bone deposits were eventually discovered. Only after initiating 177Lu-DOTATATE PRRT did the patient achieve sustained clinical improvement (symptoms), biochemical improvement (hormone levels), and structural improvement (tumor shrinkage).\n\nThe authors note that the limited published cases of PRRT in metastatic PitNET show mostly favorable outcomes: tumor stability and/or shrinkage with limited adverse events (primarily mild blood count reductions).","whyItMatters":"Metastatic pituitary tumors are among the most challenging cancers to treat, with no standard therapy and limited options after surgery and radiation fail. This case demonstrates that PRRT — which uses a peptide to deliver targeted radiation directly to tumor cells expressing somatostatin receptors — can succeed where everything else has failed. As PRRT becomes more widely available (it's FDA-approved for other neuroendocrine tumors), this evidence supports expanding its use to aggressive pituitary tumors.","specificNumbers":"","methodology":"This is a single-patient case report describing the clinical course of a 55-year-old male with metastatic ACTH-secreting PitNET. The report chronicles his treatment history, the detection of metastatic disease, and the response to 177Lu-DOTATATE PRRT. The authors also review the limited published literature on PRRT use in metastatic PitNET.","limitations":"This is a single case report — the lowest level of clinical evidence. Individual patient responses cannot be generalized to all patients with metastatic PitNET. The patient's specific tumor biology (receptor expression, prior treatments) may have uniquely favored PRRT response. Long-term outcomes and potential late adverse effects are not fully described. Selection bias exists in published case reports, which tend to report favorable outcomes. No comparison group exists to determine whether improvement was due to PRRT or other factors."},{"rthcId":"RPEP-14168","title":"Glucose-Dependent Insulinotropic Polypeptide in Incretin Physiology: Role in Health and Disease.","authors":"Wolfe, M Michael; Boylan, Michael O; Chin, William W","year":2025,"journal":"Endocrine reviews, 46(4), 479-500","doi":"10.1210/endrev/bnaf006","pmid":"39951489","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14169","title":"Glucagon-like peptide-1 receptor agonists compared with bariatric metabolic surgery and the risk of obesity-related cancer: an observational, retrospective cohort study.","authors":"Wolff Sagy, Yael; Ramot, Noga; Battat, Erez; Arbel, Ronen; Reges, Orna; Dicker, Dror; Lavie, Gil","year":2025,"journal":"EClinicalMedicine, 83, 103213","doi":"10.1016/j.eclinm.2025.103213","pmid":"40599584","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14170","title":"Clinical development of oral semaglutide for the treatment of type 2 diabetes mellitus: focusing on early phase clinical trials.","authors":"Won, Heejae; Cho, Joo-Youn; Lee, SeungHwan","year":2025,"journal":"Translational and clinical pharmacology, 33(1), 1-9","doi":"10.12793/tcp.2025.33.e3","pmid":"40206874","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The clinical development of oral semaglutide progressed through key phases:\n\n- Phase 1: Demonstrated dose-dependent HbA1c and body weight reductions; characterized pharmacokinetics and drug interactions with food, disease states, and concomitant medications; established optimal dosing conditions (fasting, minimal water, 30-minute wait before eating)\n- Phase 2: Confirmed significant HbA1c and weight reductions comparable to subcutaneous semaglutide, guiding dose selection (3 mg, 7 mg, 14 mg)\n- Phase 3 (PIONEER program): Demonstrated significant HbA1c reduction, weight loss, and cardiovascular safety\n- The absorption enhancer SNAC (sodium N-[8-(2-hydroxybenzoyl)amino]caprylate) was key to enabling gastric absorption and peptide stability\n- Oral semaglutide (Rybelsus) became the first approved oral GLP-1 RA for T2DM","whyItMatters":"Making a peptide drug into a pill was considered nearly impossible for decades. Oral semaglutide's success opens the door for other oral peptide therapies — potentially transforming how patients take medications that currently require injections. Patient adherence improves dramatically when switching from injections to pills.","specificNumbers":"","methodology":"Comprehensive review of the clinical development program for oral semaglutide, covering Phase 1 (PK/PD, safety, dose-response), Phase 2 (dose-finding), and Phase 3 (PIONEER program) trials. Focuses on the pharmacological innovations that enabled oral peptide delivery.","limitations":"Oral semaglutide has lower bioavailability than the injectable form, requiring specific dosing conditions (fasting, limited water, 30-minute wait) that may reduce convenience. The SNAC technology works primarily through gastric absorption, which may not be applicable to all peptide drugs. Higher doses are needed orally to achieve comparable effects to injection."},{"rthcId":"RPEP-14171","title":"Machine learning-guided optimization of triple agonist peptide therapeutics for metabolic disease.","authors":"Wong, Anthony; Guduri, Sanskruthi; Chen, TsungYen; Patel, Kunal","year":2025,"journal":"Frontiers in bioinformatics, 5, 1687617","doi":"10.3389/fbinf.2025.1687617","pmid":"41333850","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14172","title":"Antiinflammatory actions of glucagon-like peptide-1-based therapies beyond metabolic benefits.","authors":"Wong, Chi Kin; Drucker, Daniel J","year":2025,"journal":"The Journal of clinical investigation, 135(21)","doi":"10.1172/JCI194751","pmid":"41178710","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14173","title":"Reassessment of antibody-based detection of the murine T cell GLP-1 receptor.","authors":"Wong, Chi Kin; Yusta, Bernardo; Tong, Jason C L; Broichhagen, Johannes; Hodson, David J; Drucker, Daniel J","year":2025,"journal":"Cell metabolism, 37(9), 1783-1788","doi":"10.1016/j.cmet.2025.06.012","pmid":"40902582","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14174","title":"Sequential Meals Containing Animal and Plant-Based Saturated Fats Have Differential Effects on Postprandial Gut Hormones but No Impact on Satiety Compared with Unsaturated Fats in Generally Healthy Males: Findings from the Randomized Controlled Crossover CocoHeart Study.","authors":"Wong, Gloria; Clegg, Miriam E; Ross, Damian; Lovegrove, Julie A; Jackson, Kim G","year":2025,"journal":"The Journal of nutrition, 155(9), 3020-9","doi":"10.1016/j.tjnut.2025.06.027","pmid":"40609691","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14175","title":"Anti-diabetic effects of GLP-1 receptor agonists on obese and overweight patients across diabetes status, administration routes, treatment duration and baseline characteristics: A systematic review.","authors":"Wong, Hon Jen; Lin, Norman H Y; Teo, Yao Hao; Yeo, Brian S Y; Toh, Keith Zhi Xian; Teo, Yao Neng; Chan, Mark Y; Yeo, Leonard L L; Poh, Kian Keong; Kong, William K F; Eng, Pei Chia; Tan, Benjamin Y Q; Dalakoti, Mayank; Sia, Ching-Hui","year":2025,"journal":"Diabetes, obesity & metabolism, 27(4), 1648-1659","doi":"10.1111/dom.16136","pmid":"39726212","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14176","title":"Effects of glucagon-like peptide-1 receptor agonists on blood pressure in overweight or obese patients: a meta-analysis of randomized controlled trials.","authors":"Wong, Hon Jen; Toh, Keith Zhi Xian; Teo, Yao Hao; Teo, Yao Neng; Chan, Mark Y; Yeo, Leonard L L; Eng, Pei Chia; Tan, Benjamin Y Q; Zhou, Xin; Yang, Qing; Dalakoti, Mayank; Sia, Ching-Hui","year":2025,"journal":"Journal of hypertension, 43(2), 290-300","doi":"10.1097/HJH.0000000000003903","pmid":"39445607","tags":["glp-1-receptor-agonists"],"studyType":"meta-analysis","evidenceStrength":"high","keyFinding":"Across 30 randomized controlled trials involving 37,072 patients, GLP-1 receptor agonists reduced systolic blood pressure by an average of 3.37 mmHg (95% CI -3.95 to -2.80) and diastolic blood pressure by 1.05 mmHg (95% CI -1.46 to -0.65) compared to placebo in overweight or obese patients.\n\nThe blood pressure lowering effect was consistent regardless of whether patients had diabetes, which GLP-1 drug formulation was used, how long treatment lasted, or whether the drug was injected or taken orally — with the exception of exenatide. Meta-regression found no significant correlation between blood pressure reduction and baseline age, sex, HbA1c, weight, BMI, or existing hypertension status.","whyItMatters":"High blood pressure is the leading modifiable risk factor for heart disease and stroke, and it's extremely common in overweight and obese patients. This meta-analysis provides the strongest evidence to date that GLP-1 drugs — already prescribed for diabetes and weight loss — also meaningfully lower blood pressure. A ~3.4 mmHg systolic reduction at the population level translates into significant cardiovascular risk reduction, adding another benefit to an already compelling drug class.","specificNumbers":"30 RCTs · n=37,072 · SBP -3.37 mmHg (95% CI -3.95 to -2.80) · DBP -1.05 mmHg (95% CI -1.46 to -0.65) · consistent across diabetic status and drug formulations","methodology":"Systematic review and meta-analysis of randomized controlled trials identified from PubMed, EMBASE, and CENTRAL databases (inception to February 2024). Pair-wise meta-analysis with random effects models, fixed effects meta-analysis to unify treatment effects across GLP-1 RA doses, and random effects meta-regression to explore correlations between blood pressure reduction and baseline patient characteristics.","limitations":"Individual patient data was not available, limiting subgroup analyses. The blood pressure reductions, while statistically significant, are modest in absolute terms. The exception of exenatide from the consistent class effect warrants further investigation. Studies varied in follow-up duration and specific GLP-1 RA used, introducing some heterogeneity."},{"rthcId":"RPEP-14177","title":"2FA-Platform Generates Dual Fatty Acid-Conjugated GLP-1 Receptor Agonist TE-8105 with Enhanced Diabetes, Obesity, and NASH Efficacy Compared to Semaglutide.","authors":"Wong, Mun-Teng; Lin, Pei-Hsuan; Lin, Wei-Chen; Peng, Chi-Jiun; Wright, Jon D; Lee, Hui-Ju; Chu, Hsing-Mao; Lim, Carmay; Chang, Tse Wen","year":2025,"journal":"Journal of medicinal chemistry, 68(6), 6178-6192","doi":"10.1021/acs.jmedchem.4c02153","pmid":"40044142","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14178","title":"US Population Eligibility and Estimated Impact of Tirzepatide Treatment on Obesity Prevalence and Cardiovascular Disease Events.","authors":"Wong, Nathan D; Karthikeyan, Hridhay; Fan, Wenjun","year":2025,"journal":"Cardiovascular drugs and therapy, 39(4), 837-847","doi":"10.1007/s10557-024-07583-z","pmid":"38850368","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Based on NHANES 2015-2018 data, approximately 93.4 million US adults (38% of the adult population) would meet SURMOUNT-1 trial eligibility criteria for tirzepatide treatment.\n\nApplying the weight loss effects observed with tirzepatide 15 mg in SURMOUNT-1: 70.6% (65.9 million people) would achieve at least 15% weight reduction, and 56.7% (53.0 million) would achieve at least 20% weight reduction. This would translate to 58.8% fewer people with obesity — a reduction of 55.0 million individuals.\n\nFor cardiovascular impact, estimated 10-year CVD risk dropped from 10.1% to 7.7% after modeling tirzepatide treatment effects — a 2.4% absolute risk reduction (23.6% relative). This translates to approximately 2.0 million preventable cardiovascular disease events over 10 years among the eligible population without existing CVD.","whyItMatters":"Obesity is the defining public health crisis of our time, affecting over 40% of American adults and driving cardiovascular disease, the leading cause of death. While individual clinical trial results for tirzepatide are impressive, this study puts those results in population-level perspective — showing that broad treatment could eliminate obesity in 55 million people and prevent 2 million heart events. This type of analysis helps policymakers, insurers, and health systems understand the potential return on investment in anti-obesity medications.","specificNumbers":"","methodology":"Cross-sectional analysis using NHANES 2015-2018 data to identify US adults meeting SURMOUNT-1 trial eligibility criteria (adults ≥18 with overweight/obesity). Weight changes from SURMOUNT-1 trial results at the tirzepatide 15 mg dose were applied to the eligible population to project weight outcomes and changes in obesity prevalence. Ten-year cardiovascular disease risk was calculated using BMI-based Framingham CVD risk scores before and after applying tirzepatide treatment effects on BMI and risk factors. The difference in risk was multiplied by the weighted population to estimate preventable CVD events.","limitations":"This is a modeling study, not a clinical trial — it assumes everyone eligible would respond like SURMOUNT-1 trial participants, which is unlikely in the real world. Key limitations include: trial participants are typically more adherent than the general population; the analysis assumes sustained treatment and weight loss over 10 years, but SURMOUNT-1 was a shorter trial; costs and feasibility of treating 93 million people are not addressed; the Framingham risk score may not perfectly capture modern CVD risk; and the analysis doesn't account for drug discontinuation, side effects, or weight regain after stopping treatment."},{"rthcId":"RPEP-14179","title":"Fabrication and Preclinical Evaluation of Hyaluronic Acid/Aminoclay Nanocomposite Microneedles for Noninvasive Delivery of Semaglutide in Anti-Obesity Therapy.","authors":"Woo, Chang Rim; Kim, Gyu Lin; Han, Hyo-Kyung","year":2025,"journal":"International journal of nanomedicine, 20, 11843-11858","doi":"10.2147/IJN.S544952","pmid":"41030572","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14180","title":"Perioperative Use of GLP-1 Receptor Agonists in Patients Undergoing Cardiac Procedures: A Scoping Review.","authors":"Wookey, Oscar; Galligan, Anna; Wilkie, Bruce; MacIsaac, Andrew; Paratz, Elizabeth","year":2025,"journal":"Heart, lung & circulation, 34(2), 105-117","doi":"10.1016/j.hlc.2024.11.025","pmid":"39824665","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14181","title":"Repetitive Blast Exposure Drives Chronic Pain in Female Rats.","authors":"Wright, Amirah; Murphy, Susan F; VandeVord, Pamela J","year":2025,"journal":"Journal of neuroscience research, 103(12), e70103","doi":"10.1002/jnr.70103","pmid":"41411066","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14182","title":"Protective effects of liraglutide on hypercholesterolemia-associated atherosclerosis involve attenuation of endothelial-monocyte adhesion through down-regulating the LOX-1/NF-κB signaling pathway.","authors":"Wu, Aiping; Wu, Ying; Song, Meiyan; Chen, Wen; Xu, Kaizu; Wu, Meifang; Lin, Liming","year":2025,"journal":"Scientific reports, 15(1), 27429","doi":"10.1038/s41598-025-13014-2","pmid":"40721629","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14183","title":"Advances in Neoantigen-Based Cancer Vaccines.","authors":"Wu, An-Chih; Nakamura, Yusuke; Kiyotani, Kazuma","year":2025,"journal":"Cancers, 18(1)","doi":"10.3390/cancers18010144","pmid":"41514653","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14184","title":"Novel chimeric peptides based on endomorphins and ghrelin receptor antagonist produced supraspinal antinociceptive effects with reduced acute tolerance in mice.","authors":"Wu, Bing; Cheng, Songxia; Liu, Fuyan; Wei, Jia; Liu, Yongling; Qian, Teng; Ding, Jiali; Xu, Biao; Wei, Jie","year":2025,"journal":"Biochimie, 228, 58-70","doi":"10.1016/j.biochi.2024.08.010","pmid":"39147011","tags":[],"studyType":"animal","evidenceStrength":"preliminary","keyFinding":"Two novel chimeric peptides (EM-1-DLS and EM-2-DLS) combining opioid endomorphin sequences with a ghrelin receptor antagonist fragment produced potent pain relief in mice with significantly reduced tolerance development. EM-1-DLS was approximately 8 times more potent than endomorphin-1 alone and acted through κ-opioid, μ-opioid, and ghrelin (GHS-R1α) receptors simultaneously.\n\nCritically, EM-1-DLS induced an acute tolerance ratio of only 2.33-fold, compared to 5.19-fold for endomorphin-1 alone — a roughly 55% reduction in tolerance development. Cross-tolerance ratios between the chimeric peptides and endomorphins ranged from 0.92 to 1.76, confirming reduced tolerance.","whyItMatters":"The opioid crisis has made clear the need for effective pain medications that don't rapidly build tolerance, leading to dose escalation and addiction. By fusing opioid peptides with ghrelin receptor-targeting fragments, these chimeric peptides represent a multifunctional approach to analgesia — harnessing multiple pain pathways simultaneously while reducing the tolerance that makes traditional opioids progressively less effective. This 'multitarget peptide' strategy could be a template for designing safer analgesics.","specificNumbers":"EM-1-DLS: ~8× more potent than EM-1 · Tolerance ratio: 2.33-fold (vs 5.19 for EM-1) · ~55% reduced tolerance · Cross-tolerance: 0.92–1.76 · Targets: κ-OR, μ-OR, GHS-R1α","methodology":"Two chimeric peptides were designed by combining endomorphin-1 or endomorphin-2 with the ghrelin receptor antagonist [D-Lys3]-GHRP-6. Receptor binding and functional activity were characterized in vitro. In vivo antinociceptive effects were tested in mice using the tail withdrawal test after intracerebroventricular (brain) injection. Dose-response curves, time-dependency, and acute tolerance development were assessed.","limitations":"This is an animal study with intracerebroventricular (direct brain) injection, which doesn't reflect a practical route of administration for human use. The tail withdrawal test measures only one type of pain (acute thermal). Long-term tolerance, addiction potential, and other side effects were not assessed. Translation from mouse pain models to human chronic pain remains a major challenge."},{"rthcId":"RPEP-14185","title":"Recent Advances in the Immunopathology of Axial Spondyloarthritis: with and without HLA-B27.","authors":"Wu, Brian; Tang, Amy; Nakamura, Akihiro","year":2025,"journal":"Current rheumatology reports, 27(1), 27","doi":"10.1007/s11926-025-01194-9","pmid":"40542889","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14186","title":"Less frequent dosing of GLP-1 receptor agonists as a viable weight maintenance strategy.","authors":"Wu, Calvin C; Cengiz, Anıl; Lawley, Sean D","year":2025,"journal":"Obesity (Silver Spring, Md.), 33(7), 1232-1236","doi":"10.1002/oby.24302","pmid":"40415172","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14187","title":"Comparative dementia risk with GLP1 receptor agonists, SGLT2 inhibitors, or DPP4 inhibitors: a population-based cohort study.","authors":"Wu, Che-Yuan; Alkabbani, Wajd; Shah, Baiju R; Kapral, Moira K; Edwards, Jodi D; Maxwell, Colleen J; Swardfager, Walter","year":2025,"journal":"Alzheimer's research & therapy, 17(1), 269","doi":"10.1186/s13195-025-01929-x","pmid":"41420258","tags":[],"studyType":"cohort","evidenceStrength":"strong","keyFinding":"In this large UK cohort of adults aged 60+ with type 2 diabetes, SGLT2 inhibitors were associated with a 14% lower dementia risk compared to DPP4 inhibitors in the intention-to-treat analysis (HR 0.86, 95% CI 0.79–0.94), increasing to a 30% reduction with continuous use (HR 0.70, 95% CI 0.60–0.82). GLP-1 receptor agonists showed no significant difference from DPP4 inhibitors in the intention-to-treat analysis (HR 0.95, 95% CI 0.87–1.04), but continuous GLP-1RA use was associated with a 21% lower risk (HR 0.79, 95% CI 0.64–0.97).\n\nGLP-1RAs and SGLT2 inhibitors showed comparable dementia risk in head-to-head comparison (HR 0.98, 95% CI 0.87–1.11).","whyItMatters":"With the global rise of both type 2 diabetes and dementia, identifying diabetes drugs that also protect brain health could be transformative. This study provides real-world evidence that SGLT2 inhibitors — and possibly GLP-1 receptor agonists with sustained use — may reduce dementia risk in older adults with diabetes. These findings could influence treatment selection for millions of patients, especially since these drugs are already widely prescribed.","specificNumbers":"n=13,965 GLP1-RA vs DPP4i pairs · n=25,533 SGLT2i vs DPP4i pairs · n=14,214 GLP1-RA vs SGLT2i pairs · SGLT2i vs DPP4i ITT: HR 0.86 (0.79–0.94) · SGLT2i continuous use: HR 0.70 (0.60–0.82) · GLP1-RA continuous use vs DPP4i: HR 0.79 (0.64–0.97) · Mean follow-up: 4.9–6.5 years","methodology":"This was a target trial emulation cohort study using UK Clinical Practice Research Datalink electronic health records. Three pairwise comparisons were made between new users of GLP-1RAs, SGLT2 inhibitors, and DPP4 inhibitors in adults aged ≥60 with type 2 diabetes and no pre-existing cognitive impairment. Propensity score overlap weighting was used to balance groups. Both intention-to-treat and as-treated (continuous use) analyses were performed. The primary outcome was incident all-cause dementia.","limitations":"This is an observational study, so it cannot prove causation — unmeasured confounders may explain the associations. The as-treated analysis showing stronger effects with continuous use had shorter follow-up (~2.4–2.7 years) and may be affected by adherence bias. DPP4 inhibitors served as the comparator, but they may also have neuroprotective effects, potentially underestimating the benefits of the other drugs. The study used UK data, which may not generalize globally."},{"rthcId":"RPEP-14188","title":"Clinical Characteristics and Serum CGRP Level Differences Between Neurogenic Rosacea and Non-Neurogenic Rosacea.","authors":"Wu, Chenchen; Zhang, Kaoyuan; Guo, Yang; Chen, Chao; Liao, Yan; Liu, Xiaoming; Chen, Zhuoxuan; Yu, Lulu; Yu, Bo; Chen, Xiaofan; Wu, Lin","year":2025,"journal":"International journal of dermatology, 64 Suppl 2, 42-51","doi":"10.1111/ijd.70071","pmid":"41404901","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14189","title":"Thymosin α1 Combined With 2HRZE/4HR Regimen as a Potential Treatment of Pulmonary Tuberculosis: An Analysis of Immune Function, Pulmonary Function and Inflammatory Response.","authors":"Wu, Guofeng; Sun, Xuelian","year":2025,"journal":"British journal of hospital medicine (London, England : 2005), 86(9), 1-14","doi":"10.12968/hmed.2025.0235","pmid":"40994373","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14190","title":"SPOP Is a Key Trigger of Pathological Cardiac Hypertrophy and Heart Failure.","authors":"Wu, Hao; Zhuang, Yuting; Yue, Ying; Liu, Jiangqi; Han, Jin; Yao, Yiming; Xu, Xi; Liu, Junwu; Li, Yuyang; Yang, Zhenbo; Wang, Yizheng; Ning, Qiwen; Yuan, Wei; Meng, Bo; Hu, Xiaoxi; Tian, Zhongrui; Yang, Ying; Li, Jialiang; Zhang, Yang; Yang, Baofeng; Pan, Zhenwei; Lu, Yanjie","year":2025,"journal":"Circulation research, 137(9), e177-e196","doi":"10.1161/CIRCRESAHA.125.326129","pmid":"40948188","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14191","title":"Design and Synthesis of a Structurally Stabilized B‑Chain Antagonist Targeting Relaxin Family Peptide Receptor 3 (RXFP3).","authors":"Wu, Hongkang; Praveen, Praveen; Riches, Isabelle; Suresh, Devika P; Gil-Miravet, Isis; Navarro-Sánchez, Mónica; Olucha-Bordonau, Francisco E; Rosengren, K Johan; Bathgate, Ross A D; Hossain, Mohammed Akhter","year":2025,"journal":"ACS medicinal chemistry letters, 16(11), 2294-2300","doi":"10.1021/acsmedchemlett.5c00489","pmid":"41257012","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The researchers designed H3B10-22R-(13/17αF), a 14-residue single-chain stapled peptide that acts as a potent and selective RXFP3 antagonist. Compared to the previous best RXFP3 antagonist (H3B1-22R):\n\n- 12-fold improved serum stability\n- Enhanced helical structure and antagonist potency\n- High RXFP3 selectivity and binding affinity\n- Significantly inhibited RXFP3 agonist-induced food intake in rats in vivo\n\nThis represents a major simplification from the native relaxin-3 molecule (two chains, three disulfide bonds) to a drug-like single-chain peptide.","whyItMatters":"Obesity treatment needs new mechanisms beyond GLP-1 receptor agonists. The relaxin-3/RXFP3 system controls appetite and motivation at the brain level, making it a compelling target. This study overcomes a major structural hurdle in relaxin-3 drug development, producing the first drug-like RXFP3 antagonist with proven in vivo activity.","specificNumbers":"","methodology":"Researchers used peptide stapling (incorporating non-natural amino acids to lock the peptide into a helical shape) to design simplified B-chain-only analogues of relaxin-3. The lead compound was tested for RXFP3 binding affinity, selectivity, antagonist potency, and serum stability in vitro. In vivo efficacy was confirmed by measuring food intake in rats after central RXFP3 agonist administration.","limitations":"This is early-stage preclinical work. The peptide was tested only in rats for a single behavioral endpoint (food intake). Pharmacokinetics, toxicity, brain penetration with peripheral dosing, and long-term efficacy have not been assessed. The peptide still requires injection (central administration in this study), and oral bioavailability is unknown."},{"rthcId":"RPEP-14192","title":"A retrospective analysis of combination therapy with GLP-1 receptor agonists and SGLT2 inhibitors versus SGLT2 inhibitor monotherapy in patients with MASLD.","authors":"Wu, Jheng-Yan; Hsu, Wan-Hsuan; Kuo, Chia-Chih; Tsai, Ya-Wen; Liu, Ting-Hui; Huang, Po-Yu; Chuang, Min-Hsiang; Hung, Kuo-Chuan; Yu, Tsung; Lai, Chih-Cheng","year":2025,"journal":"Nature communications, 16(1), 7459","doi":"10.1038/s41467-025-62891-8","pmid":"40796776","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14193","title":"Clinical effectiveness of tirzepatide for patients with atrial fibrillation and type 2 diabetes: A retrospective cohort study.","authors":"Wu, Jheng-Yan; Tseng, Kuan-Jui; Kao, Chia-Li; Hung, Kuo-Chuan; Yu, Tsung; Lin, Yu-Min","year":2025,"journal":"Diabetes research and clinical practice, 225, 112279","doi":"10.1016/j.diabres.2025.112279","pmid":"40412626","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14194","title":"Clinical Impact of Tirzepatide on Patients With OSA and Obesity.","authors":"Wu, Jheng-Yan; Chen, Chia-Chen; Ling Tu, Wan; Hsu, Wan-Hsuan; Liu, Ting-Hui; Tsai, Ya-Wen; Huang, Po-Yu; Chuang, Min-Hsiang; Hung, Kuo-Chuan; Yu, Tsung; Lai, Chih-Cheng","year":2025,"journal":"Chest, 168(3), 785-796","doi":"10.1016/j.chest.2025.03.030","pmid":"40254150","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"After propensity score matching of 42,300 patients (21,150 per group), tirzepatide was associated with significantly reduced risks of: all-cause mortality (HR 0.443, 95% CI: 0.336-0.583, representing a 56% risk reduction), major adverse cardiovascular events (HR 0.731, 95% CI: 0.622-0.859, a 27% risk reduction), and major adverse kidney events (HR 0.427, 95% CI: 0.343-0.530, a 57% risk reduction). These associations were consistent across subgroups stratified by age (except 18-39 years), sex, BMI, and CPAP use. Sensitivity analyses confirmed robustness.","whyItMatters":"OSA affects an estimated 1 billion people worldwide and is strongly linked to cardiovascular and kidney disease. Current treatment (CPAP) addresses the apnea itself but doesn't tackle the underlying obesity driving the condition. This study provides real-world evidence that tirzepatide may improve hard clinical outcomes — death, heart events, and kidney failure — beyond just weight loss and apnea scores.","specificNumbers":"","methodology":"Retrospective cohort study using the TriNetX Global Collaborative Network, a federated electronic health records database. Included adults with OSA and obesity between January 2022 and November 2024. Patients prescribed tirzepatide were compared to those receiving lifestyle interventions. Propensity score matching balanced covariates between groups. Primary outcome was all-cause mortality; secondary outcomes included major adverse cardiovascular events (MACEs) and major adverse kidney events (MAKEs). Subgroup and sensitivity analyses were performed.","limitations":"This is an observational retrospective study, not a randomized trial — causation cannot be definitively established. Propensity score matching reduces but doesn't eliminate confounding. The TriNetX database may have coding inaccuracies and missing data. The control group receiving 'lifestyle interventions' is heterogeneous. The follow-up period (up to ~3 years) may be too short to capture long-term outcomes. The 18-39 age subgroup showed no benefit, possibly due to lower baseline event rates."},{"rthcId":"RPEP-14195","title":"Comparative clinical outcomes of adults with obstructive sleep apnea and comorbid obesity receiving tirzepatide versus bariatric metabolic surgery: A Multi-Institutional propensity score matched study.","authors":"Wu, Jheng-Yan; Lin, Yu-Min; Hsu, Wan-Hsuan; Liu, Ting-Hui; Tsai, Ya-Wen; Huang, Po-Yu; Chuang, Min-Hsiang; Yu, Tsung; Lai, Chih-Cheng","year":2025,"journal":"Diabetes research and clinical practice, 226, 112294","doi":"10.1016/j.diabres.2025.112294","pmid":"40456414","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"After propensity score matching, 10,269 patients in each group were compared:\n- Primary composite outcome (mortality + MACE + MAKE): No significant difference (HR 0.87, 95% CI 0.66-1.15, p = 0.335)\n- All-cause mortality: No significant difference (HR 0.90, 95% CI 0.56-1.46, p = 0.672)\n- MACE: No significant difference (HR 1.16, 95% CI 0.85-1.56, p = 0.344)\n- MAKE (kidney events): Tirzepatide significantly lower (HR 0.60, 95% CI 0.42-0.87, p = 0.006) — a 40% reduction in kidney complications","whyItMatters":"Bariatric surgery is highly effective for obesity but is invasive, carries surgical risks, and requires permanent anatomical changes. If a peptide injection can achieve similar clinical outcomes — especially with better kidney protection — it fundamentally changes the treatment decision for millions of obese patients with sleep apnea. This study provides the first large-scale head-to-head comparison in this specific population.","specificNumbers":"","methodology":"Retrospective cohort study using the TriNetX Global Collaborative Network, a multi-institutional electronic health records database. Adults with OSA and comorbid obesity were stratified into tirzepatide and bariatric surgery groups. Propensity score matching balanced baseline characteristics, resulting in 10,269 well-matched patients per group. Primary outcomes were a composite of all-cause mortality, MACE, and MAKE.","limitations":"This is a retrospective observational study, not a randomized trial, so residual confounding may exist despite propensity matching. The TriNetX database may not capture all relevant outcomes or follow-up data. The study period for tirzepatide is relatively short (the drug was approved in 2022), so long-term outcomes compared to surgery — which has decades of data — cannot be assessed. Different types of bariatric surgery (sleeve, bypass) were grouped together, though they have different efficacy profiles."},{"rthcId":"RPEP-14196","title":"Comparative effectiveness of tirzepatide versus bariatric metabolic surgery in adults with metabolic-associated steatotic liver disease and obesity: a multi-institutional propensity score-matched study.","authors":"Wu, Jheng-Yan; Lin, Yu-Min; Hsu, Wan-Hsuan; Liu, Ting-Hui; Tsai, Ya-Wen; Huang, Po-Yu; Chuang, Min-Hsiang; Yu, Tsung; Lai, Chih-Cheng","year":2025,"journal":"Hepatology international, 19(5), 1087-1097","doi":"10.1007/s12072-025-10857-9","pmid":"40668509","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14197","title":"Comparing clinical outcomes of adults with obesity receiving tirzepatide versus bariatric metabolic surgery: A multi-institutional propensity score-matched study.","authors":"Wu, Jheng-Yan; Chan, Song-En; Hsu, Wan-Hsuan; Kuo, Chia-Chih; Tsai, Ya-Wen; Liu, Ting-Hui; Huang, Po-Yu; Chuang, Min-Hsiang; Yu, Tsung; Lai, Chih-Cheng","year":2025,"journal":"Diabetes, obesity & metabolism, 27(6), 3357-3366","doi":"10.1111/dom.16353","pmid":"40109063","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14198","title":"Glucagon-Like Peptide-1 Receptor Agonists and Dementia Risk Reduction in Older Adults With Type 2 Diabetes: A Retrospective Cohort Study.","authors":"Wu, Jheng-Yan; Lin, Yu-Min; Hsu, Wan-Hsuan; Liu, Ting-Hui; Tsai, Ya-Wen; Huang, Po-Yu; Chuang, Min-Hsiang; Yu, Tsung; Lai, Chih-Cheng","year":2025,"journal":"Journal of the American Medical Directors Association, 26(12), 105901","doi":"10.1016/j.jamda.2025.105901","pmid":"41075815","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1RA use was associated with a 42% lower risk of dementia compared to DPP-4 inhibitors (HR 0.58, 95% CI 0.55–0.61, P < .0001). The drugs were also linked to a 38% lower risk of Alzheimer's disease (HR 0.62) and a 38% lower risk of vascular dementia (HR 0.62). Patients on GLP-1RAs were 24% less likely to be prescribed dementia-related medications (HR 0.76). These risk reductions were consistent across subgroups stratified by age, sex, and specific GLP-1RA type.","whyItMatters":"With dementia rates rising globally and no cure available, finding that a widely prescribed diabetes medication class may substantially reduce dementia risk could have enormous public health implications. If confirmed in randomized trials, this could reshape how clinicians choose diabetes treatments for older adults.","specificNumbers":"","methodology":"This was a retrospective cohort study using electronic health records from 134 healthcare organizations worldwide via the TriNetX network. Researchers used an active-comparator, new-user design with 1:1 propensity score matching to compare 82,689 GLP-1RA users with 82,689 DPP-4i users aged 65+ with type 2 diabetes. Cox proportional hazards models estimated dementia risk.","limitations":"As a retrospective observational study, it cannot establish causation — unmeasured confounders may explain the association. The use of electronic health records means some dementia cases may be underdiagnosed or miscoded. The comparison was against DPP-4 inhibitors specifically, not a placebo, so the results reflect relative rather than absolute risk reduction. Follow-up duration was not specified."},{"rthcId":"RPEP-14199","title":"Tirzepatide and major adverse limb events: Insights from a multicenter real-world analysis in PAD and diabetes patients.","authors":"Wu, Jheng-Yan; Tu, Wan-Ling; Yu, Tsung; Liao, Kuang-Ming; Lin, Yu-Min","year":2025,"journal":"Diabetes research and clinical practice, 222, 112083","doi":"10.1016/j.diabres.2025.112083","pmid":"40049522","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14200","title":"Tirzepatide and the Prevention of Heart Failure in Obesity: A Multi-Center Cohort Study Using the TriNetX Database.","authors":"Wu, Jheng-Yan; Tseng, Kuan-Jui; Kao, Chia-Li; Hung, Kuo-Chuan; Yu, Tsung; Lin, Yu-Min","year":2025,"journal":"European journal of preventive cardiology","doi":"10.1093/eurjpc/zwaf663","pmid":"41123417","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14201","title":"Prediction of three-year all-cause mortality in patients with heart failure and atrial fibrillation using the CatBoost model.","authors":"Wu, Jiacan; Tao, Guanghong; Xie, Siyuan; Yang, Han; Qi, Fenglin; Bao, Naiyue; Li, Zhuo; Chang, Guanglei; Xiao, Hua","year":2025,"journal":"BMC cardiovascular disorders, 25(1), 466","doi":"10.1186/s12872-025-04928-w","pmid":"40615809","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The CatBoost machine learning model achieved the highest AUC of 0.809 for predicting three-year all-cause mortality in HF-AF patients, outperforming five other ML approaches. Of 558 patients, 215 (38.5%) reached the primary endpoint of death during median follow-up of 1,185 days.\n\nSHAP analysis identified the top five predictive features: NYHA heart failure classification, absolute lymphocyte count (ALC), high-sensitivity C-reactive protein (hs-CRP), B-type natriuretic peptide (BNP), and age. Notable feature interactions were found between lymphocyte count and NYHA class, and between lymphocyte count and BNP, suggesting these biomarkers provide complementary prognostic information.","whyItMatters":"Heart failure with atrial fibrillation is extremely common and deadly, but predicting which patients face the highest risk is difficult using traditional clinical scores alone. BNP — a peptide biomarker already widely measured in heart failure — was confirmed as one of the strongest predictors, and its interaction with lymphocyte count suggests that combining peptide biomarkers with immune markers could improve risk stratification beyond what either achieves alone.","specificNumbers":"","methodology":"Retrospective cohort study of 558 HF-AF patients admitted in 2018 with median follow-up of 1,185 days. The Boruta algorithm and LASSO regression selected 14 key variables. Six ML models were trained using 10-fold cross-validation on a 70/30 train-test split, optimized via grid search, and evaluated across 12 performance metrics. SHAP analysis was used for model interpretation and feature interaction analysis.","limitations":"This was a single-center retrospective study with a moderate sample size (558 patients), which limits generalizability. External validation in an independent cohort was not performed. The model was trained on 2018 admission data, and treatment patterns may have changed since then. The study did not compare the ML model's performance against established clinical risk scores (like CHA₂DS₂-VASc) head-to-head."},{"rthcId":"RPEP-14202","title":"The efficacy and safety of thymosin α1 for sepsis (TESTS): multicentre, double blinded, randomised, placebo controlled, phase 3 trial.","authors":"Wu, Jianfeng; Pei, Fei; Zhou, Lixin; Li, Weiqin; Sun, Renhua; Li, Yimin; Wang, Zheng; He, Zhijie; Zhang, Xiaofei; Jin, Xiaodong; Long, Yun; Cui, Wei; Wang, Chunting; Chen, Erzhen; Zeng, Jun; Yan, Jing; Lin, Qinhan; Zhou, Feihu; Huang, Lei; Shang, You; Duan, Meili; Zheng, Wei; Zhu, Duming; Kou, Qiuye; Zhang, Shihong; Liu, Yin; Yao, Chen; Shang, Meixia; Peng, Sui; Zhou, Qian; Cheng, Kar Keung; Guan, Xiangdong","year":2025,"journal":"BMJ (Clinical research ed.), 388, e082583","doi":"10.1136/bmj-2024-082583","pmid":"39814420","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14203","title":"GLP-1RA Semaglutide Delays the Progression of ADPKD Through Regulation of Glycolysis, Mitochondria Function and Ketosis.","authors":"Wu, Jiao; Cheng, Alice Shasha; Weimbs, Thomas; Harris, Peter C; Zhou, Julie Xia; Li, Xiaogang","year":2025,"journal":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 39(16), e70944","doi":"10.1096/fj.202501605R","pmid":"40815122","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14204","title":"Patterns and costs associated with glucagon-like peptide-1 receptor agonist use in US adults with type 2 diabetes.","authors":"Wu, Jun; Perez, Alexandra; Sullivan, Patrick W","year":2025,"journal":"Journal of managed care & specialty pharmacy, 31(10), 1029-1038","doi":"10.18553/jmcp.2025.31.10.1029","pmid":"41004212","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14205","title":"Bioactive Peptides from Sodium Caseinate Hydrolysate with High Oral Absorption Regulate Blood Glucose in Type 2 Diabetic Mice via Inhibition of DPP-IV and Stimulation of GLP-1.","authors":"Wu, Pei-Yu; Hsieh, Cheng-Hong; Iqbal, Ali; Lin, Yu-Shun; Cheng, Ming-Wei; Chang, Ling-Hsuan; Huang, Shang-Ming; Hsu, Kuo-Chiang","year":2025,"journal":"Foods (Basel, Switzerland), 14(11)","doi":"10.3390/foods14111953","pmid":"40509480","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14206","title":"Chelation of cerium (III) with fish skin collagen peptides: Improving the in vitro stability and bioavailability of inorganic cerium.","authors":"Wu, Peihan; Tu, Zongcai; Wang, Hui; Hu, Yueming; Cheng, Jie; Liu, Hai-Bin; Wen, Pingwei","year":2025,"journal":"Food research international (Ottawa, Ont.), 217, 116821","doi":"10.1016/j.foodres.2025.116821","pmid":"40597531","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14207","title":"Tirzepatide alleviates non-alcoholic fatty liver disease by regulating lipid metabolism through activation of the AMPK/NF-κB signaling pathway.","authors":"Wu, Pengfei; Xu, Hao; Zeng, Yuqiao; Shen, Ao; Zhang, Cheng; Wu, Bing; Zhang, Xinyue; Zhang, Han; He, Yiyu; Wang, Likun","year":2025,"journal":"American journal of translational research, 17(12), 9555-9565","doi":"10.62347/SNZK2023","pmid":"41552345","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14208","title":"A meta-analysis on the risk of esophageal cancer in type 2 diabetes patients treated with GLP-1 receptor agonists.","authors":"Wu, Qi; Zeng, Yan; Liu, Yong; Teng, Fangyuan; Zhou, Tiejun; Guo, Man; Jiang, Zongzhe; Xu, Yong","year":2025,"journal":"Frontiers in endocrinology, 16, 1532587","doi":"10.3389/fendo.2025.1532587","pmid":"40182628","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The pooled relative risk of esophageal cancer in patients using GLP-1 receptor agonists compared to control agents was 0.46 (95% CI 0.13-1.59; p=0.725; I²=0%), indicating no increased risk and a non-significant trend toward reduced risk. There was no heterogeneity between studies (I²=0%).\n\nSubgroup analyses stratified by age, intervention duration, BMI category, and indication (T2DM vs. obesity) consistently showed no association between GLP-1 RA use and increased esophageal cancer risk. No significant within-class differences were found among different GLP-1 receptor agonists.","whyItMatters":"As GLP-1 receptor agonists become some of the most prescribed drugs worldwide, questions about long-term cancer safety are critical. Esophageal cancer was a specific concern because GLP-1 drugs can cause gastrointestinal side effects including acid reflux, which is a risk factor for esophageal cancer. This meta-analysis provides reassuring evidence from the highest quality study type — randomized controlled trials — that these drugs do not increase esophageal cancer risk.","specificNumbers":"","methodology":"Systematic literature search and meta-analysis of six randomized controlled trials comparing GLP-1 receptor agonists to control agents in adults with type 2 diabetes or obesity (total n=13,391). Bias risk and study quality were assessed. Statistical analysis used Stata 18.0 and R 4.0.2. Subgroup analyses were performed by age, treatment duration, BMI, and indication. The study was pre-registered (PROSPERO CRD42024543945).","limitations":"Only six studies met inclusion criteria, and the total number of esophageal cancer events was likely very small, limiting statistical power. The relatively short duration of most RCTs may not capture cancers that develop over many years. All data came from RCTs, which may not fully represent real-world patient populations. The non-significant p-value (0.725) means the apparent protective trend cannot be confirmed."},{"rthcId":"RPEP-14209","title":"Tadalafil plus endothelin receptor antagonists in connective tissue disease-associated pulmonary arterial hypertension: A multicenter study on exercise capacity and cardiac outcomes.","authors":"Wu, Qianwen; Ma, Hua; Li, Dongyu; Ye, Huangshu; Zhou, Zhangdi; Zhang, Ning; Zhu, Yinsu; Liu, Ting; Sun, Xiaoxuan; Zhang, Miaojia; Wang, Qiang","year":2025,"journal":"Rheumatology and immunology research, 6(2), 90-98","doi":"10.1515/rir-2025-0012","pmid":"40606847","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14210","title":"Multiplexed MALDI fingerprints for rapid detection of spontaneous bacterial peritonitis.","authors":"Wu, Qiong; Wei, Bo; Zhang, Han; Shen, Jiayi; Yang, Xinyan; Qiu, Chengtong; Tao, Jian; Wang, Shijie; Wang, Junxue; Xie, Ying; Du, Yiping; Wu, Ting","year":2025,"journal":"Diagnostic microbiology and infectious disease, 113(3), 116980","doi":"10.1016/j.diagmicrobio.2025.116980","pmid":"40602051","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"MALDI-TOF mass spectrometry combined with PLS-DA statistical analysis could rapidly distinguish spontaneous bacterial peritonitis (SBP) from noninfected ascites by analyzing protein and lipid fingerprints directly from ascitic fluid — without the need for bacterial culture. Alpha-defensins, particularly human neutrophil peptides HNP-1 and HNP-2, emerged as promising SBP biomarkers. A novel fibrinogen fragment peptide (SSSYSKQFTSSTSYNRGDSTFES) was associated with non-infected ascites. Combining HNP-2 with this fibrinogen peptide achieved an AUC of 0.956 for SBP diagnosis — far superior to current clinical indicators.","whyItMatters":"Spontaneous bacterial peritonitis is a life-threatening infection in patients with liver cirrhosis and ascites. Current diagnosis relies on culture-based methods that take 24-48 hours, during which patients can deteriorate rapidly. This MALDI-TOF approach delivers results in minutes to hours, enabling much faster antibiotic treatment. The identification of defensin peptides as biomarkers connects innate immunity (the body's first-line defense peptides) to rapid diagnostics.","specificNumbers":"AUC 0.956 (HNP-2 + fibrinogen peptide) · Results: minutes to hours vs. 24-48h culture · Lipids: 500-1000 Da · Proteins: 2,000-20,000 Da · α-defensins (HNP-1, HNP-2) = SBP biomarkers · No bacterial culture needed","methodology":"Ascitic fluid from patients with SBP and non-infected ascites was analyzed directly by MALDI-TOF mass spectrometry, measuring both lipid species (500-1000 Da) and intact proteins (2,000-20,000 Da). Partial least squares discriminant analysis (PLS-DA) was used to classify samples and identify discriminating features. Specific peptide biomarkers were identified and combined for diagnostic accuracy assessment (AUC analysis).","limitations":"Sample sizes are not specified in the abstract. The AUC of 0.956 is impressive but needs validation in larger, independent cohorts. MALDI-TOF mass spectrometry requires specialized equipment not available in all hospitals. The study focused on distinguishing SBP from non-infected ascites but didn't address identification of the specific bacterial species causing infection."},{"rthcId":"RPEP-14211","title":"Self-Assembled Peptide Hydrogels PPI45 and PPI47: Novel Drug Candidates for Staphylococcus aureus Infection Treatment.","authors":"Wu, Quanlong; Deng, Mengyin; Mao, Ruoyu; Yang, Na; Hao, Ya; Cao, Manli; Teng, Da; Wang, Jianhua","year":2025,"journal":"Gels (Basel, Switzerland), 11(1)","doi":"10.3390/gels11010063","pmid":"39852034","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"PPI45 and PPI47 achieved high production yields (1.82 and 2.13 g/L, respectively — 2.19x and 2.60x higher than parent peptide PPI42). Both formed self-assembled hydrogels with distinct viscosities and showed pearl necklace-like protofibril structures on TEM. They demonstrated potent anti-MRSA activity (MIC 4-16 µg/mL) with sustained bactericidal effect after drug clearance. The mechanism involved 20-38% membrane disruption at 2x MIC within 2 hours, confirmed by SEM showing membrane damage and bacterial collapse. Safety testing showed minimal hemolysis on murine red blood cells and low cytotoxicity on human HaCaT epidermal cells.","whyItMatters":"MRSA infections are a growing global health crisis, especially in wounds. Current antibiotics face resistance, and there's urgent need for alternatives. Self-assembling peptide hydrogels offer a two-in-one solution: they form a protective gel layer over wounds while actively killing bacteria. The high production yields make these peptides potentially scalable for real-world use.","specificNumbers":"","methodology":"Peptides were derived from PPI42 (a defensin-based peptide) and characterized for self-assembly (CMC, viscosity, TEM), antimicrobial activity (MIC against S. aureus ATCC43300), mechanism of action (flow cytometry for membrane disruption, SEM for morphological damage, membrane potential assays), and safety (hemolysis on murine RBCs, cytotoxicity on human HaCaT cells).","limitations":"This is an in vitro study with no animal wound infection models. The anti-MRSA activity was tested against a single reference strain (ATCC43300), and clinical MRSA isolates may respond differently. Safety was assessed on murine blood cells and a single human cell line, not in vivo tissue. Long-term stability of the hydrogels under wound conditions was not assessed. No comparison to existing wound care products was made."},{"rthcId":"RPEP-14212","title":"Effect of semaglutide on arrhythmic, major cardiovascular, and microvascular outcomes in patients with type 2 diabetes: a systematic review and meta-analysis.","authors":"Wu, Rui; Xing, Bo; Huang, Yuting; Zhou, Zijun; Sun, Boxuan; Yu, Liming; Wang, Huishan","year":2025,"journal":"Frontiers in endocrinology, 16, 1554795","doi":"10.3389/fendo.2025.1554795","pmid":"40933383","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14213","title":"Effect of semaglutide on arrhythmic, major cardiovascular, and renal outcomes in patients with overweight or obesity: a systematic review and meta-analysis.","authors":"Wu, Rui; Xing, Bo; Zhou, Zijun; Yu, Liming; Wang, Huishan","year":2025,"journal":"European journal of medical research, 30(1), 835","doi":"10.1186/s40001-025-03124-y","pmid":"40890879","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14214","title":"A Stable Delivery System for Meretrix meretrix Derived Immunomodulatory Peptide (QLNWD): Fabrication and Characterization of Glycosylated Protein Nanoparticle.","authors":"Wu, Wanyi; Wu, Zhixuan; Cai, Jiamin; Cao, Wenhong; Lin, Haisheng; Gao, Jialong; Fan, Xiuping; Zheng, Huina; Qin, Xiaoming","year":2025,"journal":"Marine drugs, 23(10)","doi":"10.3390/md23100385","pmid":"41149587","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14215","title":"Huanglian-Renshen-Decoction Maintains Islet β-Cell Identity in T2DM Mice through Regulating GLP-1 and GLP-1R in Both Islet and Intestine.","authors":"Wu, Wen-Bin; Gao, Fan; Tang, Yue-Heng; Wang, Hong-Zhan; Dong, Hui; Lu, Fu-Er; Yuan, Fen","year":2025,"journal":"Chinese journal of integrative medicine, 31(1), 39-48","doi":"10.1007/s11655-024-3915-1","pmid":"39551849","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14216","title":"Acupuncture and moxibustion in irritable bowel syndrome: a mechanistic exploration from heart rate variability to cardiac metabolism.","authors":"Wu, Wenwei; Qiu, Yuchi; Liang, Fengxia; Lu, Wei; Fu, Yimeng; Wu, Song","year":2025,"journal":"Frontiers in neurology, 16, 1716708","doi":"10.3389/fneur.2025.1716708","pmid":"41476742","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14217","title":"Enhancing GLP-1 expression via IVT mRNA and fusion protein technology for diabetes therapy.","authors":"Wu, Xiaoying; Qiao, Jingtao; Xiao, Fei; Guo, Lixin","year":2025,"journal":"Journal of pharmaceutical sciences, 114(7), 103829","doi":"10.1016/j.xphs.2025.103829","pmid":"40393145","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The GLP-1-Fc mRNA successfully encoded and produced GLP-1-Fc protein both in cell culture (HEK293T cells) and in living mice. In db/db diabetic mice, the mRNA treatment produced significantly higher GLP-1-Fc protein levels than controls, effectively reduced blood glucose after single and repeated administrations, and increased GLP-1 receptor expression. The glucose-lowering efficacy was comparable to dulaglutide (the existing GLP-1 protein drug). Intraperitoneal delivery did not cause tissue damage.","whyItMatters":"Current GLP-1 drugs require regular injections of manufactured peptides, which are expensive and complex to produce. An mRNA-based approach could fundamentally change GLP-1 therapy by letting the body produce its own therapeutic peptide — potentially offering longer-lasting effects, simpler manufacturing, and lower costs. This represents the convergence of mRNA technology (proven in vaccines) with the peptide therapeutics field.","specificNumbers":"","methodology":"GLP-1-Fc mRNA was generated using in vitro transcription and fusion protein technology. Protein expression was confirmed in HEK293T cells via Western blot and ELISA. The mRNA and dulaglutide were then administered to both normal (C57BL/6J) and diabetic (db/db) mice. Researchers measured protein levels (ELISA), GLP-1 receptor activity (cAMP assay), blood glucose, receptor expression (immunofluorescence), and tissue safety (H&E staining) after single and repeated doses.","limitations":"This is a preclinical mouse study, and translation to humans remains uncertain. The db/db mouse is a specific genetic model of diabetes that may not reflect the complexity of human type 2 diabetes. Duration of protein expression and long-term safety were not fully characterized. Intraperitoneal delivery used in mice is not a standard clinical route. The study did not compare manufacturing costs or scalability to existing peptide production."},{"rthcId":"RPEP-14218","title":"Antimicrobial Peptides for Skin Wound Healing.","authors":"Wu, Yifan; Liu, Tingting; Jin, Lili; Wang, Chuyuan; Zhang, Dianbao","year":2025,"journal":"Biomolecules, 15(11)","doi":"10.3390/biom15111613","pmid":"41301531","tags":["antimicrobial-peptides","wound-healing","skin-repair"],"studyType":"review","evidenceStrength":"review-narrative","keyFinding":"This review maps five distinct mechanisms by which antimicrobial peptides (AMPs) promote skin wound healing beyond just killing bacteria: (1) stimulating keratinocyte migration and proliferation to close wounds, (2) promoting collagen synthesis and tissue remodeling, (3) driving angiogenesis (new blood vessel formation), (4) modulating the immune response to reduce excessive inflammation, and (5) providing broad-spectrum antimicrobial activity against bacteria, fungi, and viruses.\n\nThe review also covers structural modifications (like cyclization and amino acid substitutions) and delivery systems (hydrogels, nanoparticles) that improve AMP stability and efficacy in wound settings. Several AMPs are now in clinical trials for wound healing applications.","whyItMatters":"Chronic wounds — including diabetic ulcers, burn wounds, and surgical wounds complicated by infection — are a massive healthcare burden. Traditional antibiotics only fight infection but don't actively promote healing. AMPs are unique because they do both: they kill microbes while simultaneously accelerating multiple stages of wound repair. As antibiotic resistance grows, AMPs offer a dual-action alternative.","specificNumbers":"5 healing mechanisms: keratinocyte migration, collagen synthesis, angiogenesis, immunomodulation, antimicrobial activity · Multiple AMPs in clinical trials · Structural modifications improve stability · Advanced delivery systems enhance efficacy","methodology":"Narrative review synthesizing preclinical and clinical literature on antimicrobial peptides in wound healing, covering mechanisms of action, structural optimization strategies, delivery technologies, and clinical trial status.","limitations":"This is a narrative review, not a systematic review or meta-analysis. Most wound healing data for AMPs comes from preclinical models. Clinical translation has been challenging due to AMP stability issues, potential toxicity to host cells at high concentrations, and manufacturing costs. The review does not provide specific clinical trial outcome data."},{"rthcId":"RPEP-14219","title":"Advances in Pharmacotherapies for Obesity-Related HFpEF: A Comprehensive Review.","authors":"Wu, Ying; Song, Meiyan; Chen, Xiaomin; Chen, Wen; Wu, Meifang; Lin, Liming","year":2025,"journal":"Current heart failure reports, 22(1), 33","doi":"10.1007/s11897-025-00722-z","pmid":"41160296","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The STEP-HFpEF, STEP-HFpEF DM, and SUMMIT trials demonstrated that incretin-based therapies — both GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists — significantly improved heart failure symptoms, reduced heart failure worsening events, and induced weight loss in obese HFpEF patients, regardless of whether they also had diabetes.\n\nThe review also notes that SGLT2 inhibitors and non-steroidal MRAs show prognostic benefits in HFpEF with post hoc analyses suggesting enhanced efficacy in higher-BMI subgroups. The authors propose that combining incretin-based therapies with SGLT2 inhibitors and non-steroidal MRAs may be the optimal evidence-based strategy for this patient population.","whyItMatters":"Obesity-related HFpEF is one of the fastest-growing cardiovascular conditions worldwide, with limited treatment options until recently. The demonstration that incretin-based peptide therapies can meaningfully improve both heart failure outcomes and body weight in these patients represents a paradigm shift — treating both the cardiac disease and its metabolic driver simultaneously with a single drug class.","specificNumbers":"","methodology":"This is a comprehensive narrative review synthesizing evidence from landmark randomized controlled trials (STEP-HFpEF, STEP-HFpEF DM, SUMMIT), post hoc subgroup analyses, and mechanistic studies on pharmacotherapies for obesity-related HFpEF. The review evaluates GLP-1 RAs, dual GIP/GLP-1 agonists, SGLT2 inhibitors, MRAs, ARNIs, bariatric surgery, and novel agents.","limitations":"Long-term cardiovascular mortality benefits and safety profiles of incretin-based therapies in HFpEF require further validation — the current trials primarily assessed symptoms and functional outcomes over relatively short follow-up periods. There are no randomized trials comparing bariatric surgery outcomes specifically for HFpEF. Optimal BMI thresholds for treatment, weight loss targets, and combination strategies remain undefined. Cost and access barriers to these newer medications are not fully addressed."},{"rthcId":"RPEP-14220","title":"Development of a KRP-based pH-responsive drug delivery system for solid tumors.","authors":"Wu, Yu; Pei, Jiahong; Wang, Hanzhuo; Yu, Mei; Wang, Dandan","year":2025,"journal":"Translational cancer research, 14(6), 3812-3821","doi":"10.21037/tcr-2025-1151","pmid":"40687241","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14221","title":"Long-acting PYY3 -36 analogue with semaglutide for obesity: from preclinical assessment through randomized clinical studies.","authors":"Wulff, Birgitte S; Chambers, Adam Paul; Osorto Contreras, Cynthia Karenina; Kirkeby, Katrine; Rinnov, Anders Rasmussen; Sustarsic, Riia K; Østergaard, Søren; Laabs, John E; O'Neil, Patrick M","year":2025,"journal":"Obesity (Silver Spring, Md.), 33(8), 1457-1474","doi":"10.1002/oby.24329","pmid":"40629530","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14222","title":"Glucagon-Like Peptide-1 (GLP-1a) Receptor Agonist Use in Patients Presenting for Gastroenterology Procedures: A Review of Concerns.","authors":"Wunder, Linda; Lee, Rebecca; Dalpé Welliver, Dawn","year":2025,"journal":"Gastroenterology nursing : the official journal of the Society of Gastroenterology Nurses and Associates, 48(5), 389-395","doi":"10.1097/SGA.0000000000000891","pmid":"40986735","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 receptor agonists significantly delay gastric emptying, which raises the risk of retained gastric contents in patients presenting for endoscopic procedures. This is a key safety concern because residual food in the stomach during sedation increases aspiration risk. The review highlights that healthcare practitioners need evidence-based protocols for managing GLP-1 users before, during, and after gastrointestinal procedures, including considerations about medication timing and fasting instructions.","whyItMatters":"With GLP-1 drugs now among the most prescribed medications globally, gastroenterology practices are encountering more and more patients on these drugs who need procedures like colonoscopy or upper endoscopy. The delayed gastric emptying effect — while therapeutic for appetite control — becomes a safety hazard when patients need sedation. Clear guidelines are essential to prevent aspiration events, which can be life-threatening.","specificNumbers":"","methodology":"This is a narrative review article synthesizing existing evidence and clinical concerns about GLP-1 receptor agonist use in patients undergoing gastroenterology procedures, with particular focus on delayed gastric emptying and perioperative safety.","limitations":"This is a narrative review without systematic methodology, so the coverage of evidence may not be comprehensive. The abstract does not present specific data on aspiration rates or outcomes in GLP-1 users undergoing procedures. The rapidly evolving clinical landscape around GLP-1 drugs means recommendations may change as new evidence emerges."},{"rthcId":"RPEP-14223","title":"The effect of exenatide (GLP-1a) and sitagliptin (DPP-4i) on paraoxonase 1 (PON1) activity and expression in normal and fructose-fed rats.","authors":"Wójcicka, G; Pradiuch, A; Guz, L; Wójciak, M; Rusek, M; Jamroz-Wiśniewska, A; Czechowska, G; Marciniak, S; Góralczyk, A; Bełtowski, J","year":2025,"journal":"European journal of pharmacology, 1007, 178197","doi":"10.1016/j.ejphar.2025.178197","pmid":"41043573","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14224","title":"Synthesis and evaluation of KR-12, an LL-37 fragment, and its short-chain fatty acid derivatives: selective cytotoxicity in colorectal cancer cells and anti-tumor efficacy in an azoxymethane/DSS-induced colitis-associated cancer mouse model.","authors":"Włodarczyk, Jakub; Kamysz, Elżbieta; Fichna, Jakub","year":2025,"journal":"Pharmacological reports : PR, 77(6), 1689-1702","doi":"10.1007/s43440-025-00790-x","pmid":"41091413","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14225","title":"GLP-1 Receptor Agonists in Breast Cancer: A New Frontier in Obesity and Prognosis Management.","authors":"Xande, Juliana G; Del Giglio, Auro","year":2025,"journal":"International journal of molecular sciences, 26(16)","doi":"10.3390/ijms26167744","pmid":"40869064","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14226","title":"Can good sleep quality enhance the benefits of oral collagen supplementation in the prevention of skin aging? A brief report.","authors":"Xerfan, Ellen M S; Souza, Maingredy Rodrigues; Facina, Anamaria S; Tufik, Sergio; Andersen, Monica L","year":2025,"journal":"Archives of dermatological research, 317(1), 340","doi":"10.1007/s00403-025-03860-5","pmid":"39912934","tags":[],"studyType":"review","evidenceStrength":"moderate","keyFinding":"This review of 66 studies found consistent evidence that oral hydrolyzed collagen peptide supplementation improves skin elasticity, hydration, and wrinkle reduction. Effective doses ranged from 1 to 10 g daily, with benefits appearing after 4 to 8 weeks, and a dose as low as 2.5 g/day showed measurable skin improvements. Combining collagen peptides with vitamins, minerals, and antioxidants provided additional benefits including improved skin radiance and reduced pore size.\n\nThe review also identified that poor sleep impairs skin hydration, increases transepidermal water loss, and reduces elasticity — suggesting that sleep quality may significantly modulate the effectiveness of collagen peptide supplementation.","whyItMatters":"Collagen peptide supplements are one of the most popular consumer peptide products, but the evidence base is often unclear to consumers. This review consolidates clinical evidence across dozens of studies, confirming meaningful skin benefits while introducing the novel idea that sleep quality could be a key factor determining how well collagen supplements work.","specificNumbers":"","methodology":"Literature search of PubMed identifying 1,117 articles, with 66 reviewed in full. The review covered clinical studies on oral collagen peptide effects on skin, and separately examined studies on sleep-collagen metabolism interactions. Most included studies involved women in their 30s-40s.","limitations":"This is a brief narrative review, not a systematic review or meta-analysis, so it lacks formal quality assessment of included studies. The sleep-collagen interaction is hypothesized based on separate lines of evidence rather than studies that directly tested collagen supplementation combined with sleep interventions. Most studies involved women, limiting generalizability to men."},{"rthcId":"RPEP-14227","title":"Dulaglutide accelerates diabetic wound healing by suppressing Nrf2-dependent ferroptosis in diabetic mice.","authors":"Xi, Liuqing; Du, Juan; Lu, Yan; Xue, Wen; Xia, Yuxuan; Chen, Tingxu; Xiao, Yang; Xu, Nuo; Wang, Yansheng; Gao, Jianfang; Li, Wenyi; Huang, Shan","year":2025,"journal":"Peptides, 185, 171366","doi":"10.1016/j.peptides.2025.171366","pmid":"39954860","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In db/db diabetic mice with full-thickness wounds, dulaglutide delivered via subcutaneous injection around the wound:\n\n- Increased VEGF expression and Ki67 proliferation marker, accelerating wound closure\n- In vitro, promoted keratinocyte (HaCaT cell) proliferation and migration under high glucose conditions\n- High glucose induced ferroptosis markers: increased Fe²⁺, ROS, and MDA; decreased GSH and SOD\n- Dulaglutide reversed all ferroptosis markers\n- Mechanism: dulaglutide activated Nrf2 signaling, increasing Gpx4 and Slc7a11 expression to inhibit ferroptosis\n- Results consistent in both in vivo (mouse wounds) and in vitro (cell culture) models","whyItMatters":"Diabetic wounds are a massive clinical problem — they precede most non-traumatic amputations. This study reveals that ferroptosis (iron-dependent cell death) is a key mechanism in delayed diabetic wound healing and that a GLP-1 drug can specifically counteract it. Since dulaglutide is already FDA-approved for diabetes, repurposing it for wound healing could be relatively straightforward clinically.","specificNumbers":"","methodology":"Full-thickness wounds were created on db/db diabetic mice, and dulaglutide was injected subcutaneously around the wound perimeter. Wound closure rates were monitored over time. In vitro, HaCaT keratinocytes were treated with dulaglutide under high glucose conditions. Cell viability was assessed by CCK-8 and EdU assays. Ferroptosis was evaluated by measuring Fe²⁺, ROS, MDA, GSH, SOD levels, and ferroptosis marker expression. Nrf2 pathway activation was confirmed by protein expression analysis.","limitations":"This was a preclinical study in genetically diabetic mice, which may not fully represent human diabetic wound healing. The dulaglutide was injected around the wound rather than given systemically, so the local versus systemic contribution is unclear. Long-term effects and optimal dosing for wound healing were not assessed. The study did not compare dulaglutide to other GLP-1 drugs previously shown to promote wound healing."},{"rthcId":"RPEP-14228","title":"Injectable Thymosin β4-Modified Hyaluronic Acid Hydrogel with Exosomes for Stem Cell Homing and Neuronic-Angiogenic-Osteogenic Coupled Cranial Repair.","authors":"Xi, Yanhai; Zhang, Zhen; Zhao, Zixuan; Qiu, Ba; Wang, Weiheng; Xu, Guohua; Sun, Zheru; Shi, Feng; Liang, Wenkui; Wu, Jun","year":2025,"journal":"ACS nano, 19(25), 22710-22724","doi":"10.1021/acsnano.4c10386","pmid":"40528381","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14229","title":"Revealing Anisotropic Growth of Liraglutide Oligomers by Native Ion Mobility Mass Spectrometry and Molecular Dynamics Simulation.","authors":"Xi, Zhenyu; Kuo, Syuan-Ting; Cong, Xiao; Yan, Xin; Russell, David H","year":2025,"journal":"ACS central science, 11(7), 1154-1165","doi":"10.1021/acscentsci.5c00431","pmid":"40726781","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14230","title":"Clinical Characteristics and Prognosis of Acute Heart Failure in Patients with Chronic Obstructive Pulmonary Disease.","authors":"Xia, Han; Li, Junlei; Dong, Jianzeng","year":2025,"journal":"The American journal of cardiology, 257, 101-109","doi":"10.1016/j.amjcard.2025.08.020","pmid":"40819680","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14231","title":"Multiparametric MRI Evaluation of Liver Fat and Iron after Glucagon-like Peptide-1 Receptor and Glucagon Receptor Dual-Agonist Treatment in a High-Fat Diet-induced Mouse Model.","authors":"Xia, Huimin; Min, Yuqin; Wang, Yuhua; Gao, Siyu; Wang, Hailing; Yan, Fuhua; Liu, Ruixin; Wang, Jiqiu; Gu, Xuejiang; Bo, Tingting","year":2025,"journal":"Radiology, 316(2), e243780","doi":"10.1148/radiol.243780","pmid":"40828048","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14232","title":"Semaglutide vs. dulaglutide for glycemic and weight control in patients with type 2 diabetes mellitus: A systematic review and meta‑analysis.","authors":"Xia, Lili; Li, Huihua; Huang, Shan; Shen, Lisha","year":2025,"journal":"Biomedical reports, 22(3), 35","doi":"10.3892/br.2024.1913","pmid":"39781043","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14233","title":"The Application Value of Brain Natriuretic Peptide in the Prognostic Evaluation of Patients With Chronic Left Heart Failure.","authors":"Xiang, Congling; Zhou, Weier","year":2025,"journal":"Cardiovascular therapeutics, 2025, 9353377","doi":"10.1155/cdr/9353377","pmid":"40861247","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14234","title":"Safety and efficacy of GLP-1/FGF21 dual agonist HEC88473 in MASLD and T2DM: A randomized, double-blind, placebo-controlled study.","authors":"Xiang, Lin; Wang, Guixia; Zhuang, Yulei; Luo, Lin; Yan, Jiangyu; Zhang, Hong; Li, Xiaojiao; Xie, Can; He, Qingwei; Peng, Yuyu; Chen, Hong; Li, Qianqian; Li, Xiaoping; Guo, Linfeng; Lv, Guoyue; Ding, Yanhua","year":2025,"journal":"Journal of hepatology, 82(6), 967-978","doi":"10.1016/j.jhep.2024.12.006","pmid":"39709140","tags":["glp-1-agonists","fatty-liver","diabetes","dual-agonist"],"studyType":"rct","evidenceStrength":"moderate","keyFinding":"HEC88473, a GLP-1/FGF21 dual agonist given as weekly subcutaneous injections for 5 weeks, produced dose-proportional reductions in liver fat measured by MRI-PDFF. The best-performing dose (30.6 mg) achieved a 47.21% relative reduction in liver fat (p = 0.0143) versus 15.05% with placebo. Patients with higher baseline fat (PDFF >8%) were more likely to achieve >30% relative reductions.\n\nBlood sugar control also improved significantly: HbA1c dropped by up to 1.10% in the 68.0 mg group versus 0.31% with placebo, along with reductions in fasting and post-meal glucose levels. Lipid profiles improved across dose groups. The drug was generally well tolerated, with GI disorders being the most common adverse event (48.3%), mostly mild to moderate.","whyItMatters":"MASLD (formerly called NAFLD/NASH) affects roughly 30% of adults globally and has no widely approved pharmacological treatment beyond the recently approved resmetirom. The combination of GLP-1 and FGF21 activity is scientifically compelling because GLP-1 addresses appetite and blood sugar while FGF21 directly targets liver fat metabolism and lipid handling. Getting a 47% liver fat reduction in just 5 weeks is striking — most MASLD trials run 24-52 weeks. This drug's ability to simultaneously improve liver fat, blood sugar, and lipids could make it a single treatment for the cluster of metabolic problems that define metabolic syndrome.","specificNumbers":"n=60; liver fat ↓47.21% (30.6mg, p=0.0143) vs ↓15.05% placebo; HbA1c ↓1.10% (68mg) vs ↓0.31% placebo; 48.3% GI adverse events; 5 doses tested; 5-week treatment","methodology":"Randomized, double-blind, placebo-controlled, multiple-ascending-dose Phase Ib/IIa trial. 60 patients with MASLD and T2DM randomized 10:2 to HEC88473 (5 dose levels: 5.1-68.0 mg) or placebo via weekly subcutaneous injection for 5 weeks. Primary outcomes included liver fat by MRI-PDFF, HbA1c, fasting and postprandial glucose, and lipid profiles. Safety assessed through adverse event monitoring.","limitations":"This was a small Phase Ib/IIa trial (60 patients total, only 10 per dose group). The 5-week treatment duration is extremely short — longer studies are needed to confirm sustained efficacy and assess safety over months to years. No histological endpoints (liver biopsy) were assessed, which are considered the gold standard for MASLD trials. The 10:2 randomization ratio means only 2 placebo patients per cohort, limiting statistical power for safety comparisons. All patients were from China, so results may not generalize to other populations. The GI adverse event rate of 48.3% warrants monitoring at longer durations."},{"rthcId":"RPEP-14235","title":"From garlic proteins to bioactive peptides: A computer-aided screening for saltiness-enhancers and angiotensin I-converting enzyme inhibitors with mechanistic and kinetic analysis.","authors":"Xiang, Lu; Qiu, Zhichang; Zheng, Zhenjia; Lu, Xiaoming; Chen, Haihua; Qiao, Yiteng","year":2025,"journal":"Food chemistry, 494, 146138","doi":"10.1016/j.foodchem.2025.146138","pmid":"40912119","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14236","title":"Unlocking the potential of garlic by-product protein: Ultrasound-induced structural modification and fabrication of an ACE inhibitory peptide targeting endothelial dysfunction.","authors":"Xiang, Lu; Qiu, Zhichang; Zheng, Zhenjia; Chen, Haihua; Qiao, Yiteng","year":2025,"journal":"Ultrasonics sonochemistry, 123, 107642","doi":"10.1016/j.ultsonch.2025.107642","pmid":"41151420","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14237","title":"Nobiletin Alleviates Npy1r-Mediated Insulin Secretion Deficiency of Islet β-Cells via the Clock-Modulatory Signaling.","authors":"Xiang, Qianru; Chen, Xiao; Tang, Enhui; Chen, Zhi; Xia, Zijun; Liao, Wenzhen","year":2025,"journal":"Molecular nutrition & food research, 69(21), e70208","doi":"10.1002/mnfr.70208","pmid":"40913544","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14238","title":"Long term cost-effectiveness analysis of IDegLira in the treatment of type 2 diabetes patients compared to GLP-1RA added to basal insulin after IDegLira entered the national reimbursement drug list in China.","authors":"Xiao, Dunming; Weng, Junling; Zhang, Lei; Xing, Chang; Wei, Yan; Chen, Yingyao","year":2025,"journal":"PloS one, 20(2), e0310497","doi":"10.1371/journal.pone.0310497","pmid":"39913436","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14239","title":"CX3CR1 modulates acute disc herniation-induced pain via regulating local inflammation and spinal microglia activation.","authors":"Xiao, Li; Zhang, Yi; Xing, Yuan; Yang, Hanzhi; Shen, Mia A; James, Nina E; Sung, Sun-Sang J; Kuan, Chia-Yi; Jin, Li; Li, Xudong","year":2025,"journal":"Osteoarthritis and cartilage, 33(11), 1316-1331","doi":"10.1016/j.joca.2025.08.017","pmid":"40907650","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14240","title":"Modulating the elasticity of milk exosome-based hybrid vesicles to optimize transepithelial transport and enhance oral peptide delivery.","authors":"Xiao, Peifu; Yuan, Haoyang; Liu, Hongbing; Guo, Chen; Feng, Yupeng; Zhao, Wenpeng; Zhao, Bohang; Yin, Tian; Zhang, Yu; He, Haibing; Tang, Xing; Gou, Jingxin","year":2025,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 380, 36-51","doi":"10.1016/j.jconrel.2025.01.090","pmid":"39892650","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14241","title":"Aptamer Functionalized Liposomes Co-Loaded with Exenatide-4 and Coenzyme Q10 Ameliorate Type 2 Diabetes Mellitus by Improving Pancreatic β Cell Function.","authors":"Xiao, Shangying; Rao, Lei; Yan, Canying; Nie, Ling; Wang, Leiqi; Zhao, Yingyin; Zhang, Shihao; Zhan, WeiMao; Qin, Dongyun; Zhuang, Manjiao","year":2025,"journal":"International journal of nanomedicine, 20, 3363-3378","doi":"10.2147/IJN.S510240","pmid":"40125440","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14242","title":"Recombinant expression of a novel Mytilus defensin in Pichia pastoris.","authors":"Xiao, Wenhui; Song, Fang; Chen, Chuanyue; Huang, Fangfang; Yang, Qiaomei; Zhang, Xiaolin; Liao, Zhi","year":2025,"journal":"Sheng wu gong cheng xue bao = Chinese journal of biotechnology, 42(2), 852-864","doi":"10.13345/j.cjb.250418","pmid":"41755609","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Recombinant myticofensin-B1 (65 amino acids, 6 conserved cysteine residues forming 3 disulfide bonds) was successfully expressed in Pichia pastoris with a confirmed molecular weight of 8,849.9 Da matching the theoretical prediction. LC-MS/MS confirmed structural fidelity.\n\nThe recombinant peptide demonstrated broad-spectrum antimicrobial activity with stronger inhibition against Gram-negative bacteria. Scanning electron microscopy revealed the peptide affected different bacterial species through different physical mechanisms. Importantly, it showed very low hemolytic activity against sheep red blood cells (indicating safety for blood cells) and weak cytotoxicity against human A549 lung cancer cells.","whyItMatters":"Antimicrobial resistance is a growing global crisis, and natural antimicrobial peptides from marine organisms represent a vast untapped reservoir of potential new antibiotics. However, producing these complex peptides at scale has been a major bottleneck — bacterial expression systems often fail because the peptides' positive charges and disulfide bonds are toxic or incompatible. This study solves that problem for mussel defensins by establishing a yeast-based production platform, opening the door to large-scale production and further drug development.","specificNumbers":"","methodology":"The gene encoding mature myticofensin-B1 was codon-optimized for yeast expression, cloned into a pPICZαA vector, and expressed in Pichia pastoris strain GS115. The recombinant peptide was characterized by liquid chromatography-tandem mass spectrometry (LC-MS/MS) for structural verification. Antimicrobial activity was tested against multiple bacterial species. The peptide's effects on bacterial cells were visualized by scanning electron microscopy. Safety was assessed through hemolysis assays (sheep red blood cells) and cytotoxicity testing (human A549 lung cancer cells).","limitations":"The study focuses on production methodology and initial characterization rather than comprehensive therapeutic evaluation. Antimicrobial activity was demonstrated in vitro but not in animal infection models. The specific bacteria tested and minimum inhibitory concentrations are not detailed in the abstract. The primary application highlighted is aquaculture rather than human medicine. Long-term stability of the recombinant peptide and its behavior under physiological conditions are not addressed."},{"rthcId":"RPEP-14243","title":"A Walnut-Derived Peptide WSPSGR Alleviates Depressive-Like Behaviors in Mice via IDO1 Inhibition and Gut Microbiota-Tryptophan Axis Modulation.","authors":"Xiao, Xiao; Ma, Aijin; Chen, Zhou; Li, Siting; Xia, Junxia; Ding, Shenghua; Jia, Yingmin","year":2025,"journal":"Journal of agricultural and food chemistry, 73(42), 26780-26792","doi":"10.1021/acs.jafc.5c09940","pmid":"41074849","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14244","title":"Efficacy and safety of survodutide on glycemic control and weight loss in adults: A systematic review and meta-analysis.","authors":"Xiao, Ya-Jun; Yu, Shan; Zhang, Yan-Ling; Chen, Jiao; Liu, Yan-Qun; Liu, Xiao-Ling; Sun, Chang-Feng; Deng, Cun-Liang","year":2025,"journal":"Diabetes, obesity & metabolism, 27(12), 7062-7074","doi":"10.1111/dom.70105","pmid":"40922121","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14245","title":"Effects of glucagon-like peptide 1 receptor signaling in the dorsolateral septum on ethanol operant self-administration and relapse behaviors.","authors":"Xiao, Yuqing; Yap, Jo Ann; Ong, Zhi Yi","year":2025,"journal":"Neuropharmacology, 279, 110640","doi":"10.1016/j.neuropharm.2025.110640","pmid":"40818544","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Direct injection of exendin-4 (25 ng) into the dorsolateral septum (dLS) significantly reduced ethanol operant self-administration in male high-responder rats but had no effect in male low responders or females. In relapse tests, intra-dLS exendin-4 reduced reacquisition of ethanol self-administration — a model of relapse to drinking after abstinence — but did not affect prime + context-induced reinstatement of ethanol seeking, a model of cue/context-triggered relapse.\n\nImportantly, the alcohol reduction occurred without sustained changes in 24-hour food intake or body weight, indicating the effect was specific to reward processing rather than general appetite suppression. Retrograde tracing confirmed that the dLS receives direct input from GLP-1-producing neurons in the nucleus tractus solitarius (NTS), establishing an anatomical basis for this signaling pathway.","whyItMatters":"Alcohol use disorder affects over 400 million people globally and has few effective treatments. GLP-1 receptor agonists are generating enormous clinical interest for addiction, but understanding which brain circuits they act through is essential for developing targeted therapies. This study identifies the dorsolateral septum as a specific brain region mediating GLP-1's effects on alcohol consumption and identifies the NTS-to-dLS pathway as a neural circuit that could be targeted by future treatments.","specificNumbers":"","methodology":"Long Evans rats were given intermittent access to 20% ethanol solution before being trained in operant self-administration (lever-pressing for alcohol). On test days, rats received microinjections of exendin-4 (5 ng or 25 ng) or vehicle directly into the dorsolateral septum. For relapse testing, operant responding was first extinguished, then two relapse models were tested: reacquisition (alcohol made available again) and prime + context-induced reinstatement (alcohol priming dose plus environmental cues). Retrograde tracing mapped neural inputs to the dLS from GLP-1-expressing neurons.","limitations":"This is an animal study using direct brain injection, which is not a clinically practical delivery method. The sex-specific effects (working in males only) may not translate directly to humans, but they highlight important biological differences that need to be understood. The study used a single GLP-1 agonist (exendin-4) and may not reflect the pharmacology of other GLP-1 drugs like semaglutide or liraglutide. The distinction between high and low responders was based on the specific cohort and may not generalize across rat strains."},{"rthcId":"RPEP-14246","title":"MUC1 peptide-loaded dendritic cell vaccine boosts antitumor immunity in pancreatic cancer.","authors":"Xie, Huiping; Yang, Wenzhuo; Chen, Haodong; Zhang, Zhilan; Zhao, Zelin; Jin, Yuanyuan; Fan, Shuai; Yang, Zhaoyong","year":2025,"journal":"Frontiers in immunology, 16, 1752861","doi":"10.3389/fimmu.2025.1752861","pmid":"41607777","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14247","title":"A host defense peptide-mimicking prodrug activated by drug-resistant Gram-negative bacterial infections.","authors":"Xie, Jiayang; Zhou, Min; Cong, Zihao; Xiao, Ximian; Liu, Longqiang; Chen, Sheng; Jiang, Weinan; Wu, Yueming; Liu, Runhui","year":2025,"journal":"Science translational medicine, 17(801), eadl4870","doi":"10.1126/scitranslmed.adl4870","pmid":"40465689","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14248","title":"Efficacy of Semaglutide Injection in the Treatment of Type 2 Diabetes Mellitus and its Impact on C-Peptide Levels.","authors":"Xie, Shuying; Ye, Lan; Yang, Anyuan; Li, Xiaoyan; Yin, Ying","year":2025,"journal":"Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme, 57(6), 378-384","doi":"10.1055/a-2618-7509","pmid":"40473254","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14249","title":"Effect of astragaloside IV dripping pills on mice with dilated cardiomyopathy.","authors":"Xie, Tiantian; Wu, Dawei","year":2025,"journal":"Drug development and industrial pharmacy, 51(12), 1718-1726","doi":"10.1080/03639045.2025.2557984","pmid":"40928502","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14250","title":"Comparative Safety of GLP-1/GIP Co-Agonists Versus GLP-1 Receptor Agonists for Weight Loss in Patients with Obesity or Overweight: A Systematic Review.","authors":"Xie, Zeyu; Liang, Zhuoru; Xie, Yilin; Zheng, Guimei; Cao, Weiling","year":2025,"journal":"Diabetes, metabolic syndrome and obesity : targets and therapy, 18, 2837-2849","doi":"10.2147/DMSO.S537229","pmid":"40821754","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Key safety comparisons from the network meta-analysis:\n\n- Liraglutide 3.0mg had significantly higher overall adverse events (OR 1.53-2.00) versus both semaglutide and tirzepatide\n- Tirzepatide showed higher severe hypoglycemia risk (<54 mg/dL) and more injection-site reactions\n- Tirzepatide demonstrated superior safety for neoplasms vs liraglutide (OR 5.15, 95% CI 1.28-20.74) and vs semaglutide (OR 3.55, 95% CI 1.10-11.54)\n- Tirzepatide also showed fewer respiratory infections/nasopharyngitis\n- GLP-1 monoagonists had fewer diarrhea events but more abdominal pain/dyspepsia\n- Non-T2DM patients had significantly more adverse events than T2DM patients (P<0.05)\n- No significant differences by race, BMI, or treatment duration","whyItMatters":"As prescriptions for weight loss peptide drugs surge, understanding their comparative safety is essential for clinical decision-making. This is the first large network meta-analysis to systematically compare tirzepatide against GLP-1 monoagonists for safety in obesity. The surprising finding that dual GIP/GLP-1 agonism may confer anti-neoplasm and anti-inflammatory benefits beyond what GLP-1 alone provides could shift how clinicians think about drug selection — particularly for patients with cancer risk factors or inflammatory conditions.","specificNumbers":"","methodology":"PRISMA-compliant systematic review registered in PROSPERO (CRD42024576314). Literature was searched in PubMed, Embase, and Cochrane through August 20, 2024. Included RCTs enrolled adults with BMI ≥27 (≥25 for Asians) receiving tirzepatide 10/15mg, semaglutide 2.4mg, or liraglutide 3.0mg. Network meta-analysis used odds ratios with 95% CIs, conducted in Stata 16.1. Subgroup, sensitivity, and funnel plot analyses were performed.","limitations":"The neoplasm finding, while statistically significant, is based on a relatively small number of events and should be considered hypothesis-generating rather than definitive. The review includes only RCTs up to August 2024, so the most recent real-world data is not captured. Network meta-analysis compares drugs indirectly across trials with different populations and designs. The severe hypoglycemia finding for tirzepatide may partly reflect its stronger glucose-lowering effect. Follow-up durations in the included trials may be too short to capture long-term safety signals."},{"rthcId":"RPEP-14251","title":"Unlocking the potential of GLP-1 receptor agonists in ocular therapeutics: from molecular pathways to clinical impact.","authors":"Xie, Zhixuan; Yang, Zuyi; Tian, Dianzhe; Chen, Youxin","year":2025,"journal":"Frontiers in pharmacology, 16, 1618079","doi":"10.3389/fphar.2025.1618079","pmid":"40777992","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies multiple mechanisms by which GLP-1 receptor agonists benefit the eye:\n\n- Retinal ganglion cell (RGC) rescue via calcium channel and GABAergic modulation — protecting the nerve cells critical for vision\n- Mitochondrial protection through PINK1/Parkin-mediated mitophagy and ERK1/2-HDAC6 signaling — clearing damaged mitochondria to prevent cell death\n- Anti-inflammatory effects via cytokine reduction and immune cell recruitment inhibition\n- Retinal vascular stabilization and extracellular matrix homeostasis\n- Anti-angiogenic properties that inhibit pathological new blood vessel growth\n\nClinical evidence shows reduced glaucoma incidence and potential diabetic retinopathy benefits. However, conflicting evidence highlights context-dependent risks, including early DR worsening when glycemic control improves rapidly in poorly controlled diabetic patients.","whyItMatters":"Glaucoma and diabetic retinopathy are leading causes of blindness worldwide, and current treatments often address only specific symptoms or pathways. GLP-1 receptor agonists could represent multi-targeted disease-modifying agents that simultaneously address inflammation, oxidative stress, neurodegeneration, and abnormal blood vessel growth — the major drivers of these eye diseases. With millions of people already taking GLP-1 drugs for metabolic conditions, understanding their eye effects has immediate clinical relevance.","specificNumbers":"","methodology":"The authors conducted a comprehensive literature review searching for research and clinical trials on GLP-1 receptor agonists in ocular disease published through April 2025. The review covered cellular studies (mechanistic research), animal studies (preclinical models), and clinical observations for glaucoma, diabetic retinopathy, and other ocular conditions. Molecular pathways were analyzed to synthesize the mechanisms of ocular benefit.","limitations":"Most mechanistic evidence comes from cell and animal studies that may not translate directly to human eyes. The clinical evidence for ocular benefits is largely observational (reduced glaucoma incidence in GLP-1 users) rather than from randomized controlled trials designed for eye outcomes. The concern about early diabetic retinopathy worsening adds complexity to clinical decision-making. The review covers a broad topic that may lack depth on individual disease mechanisms. Long-term ocular safety data for GLP-1 drugs is still accumulating."},{"rthcId":"RPEP-14252","title":"Short Peptides from Asian Scorpions: Bioactive Molecules with Promising Therapeutic Potential.","authors":"Xin, Kaiyun; Sun, Ruize; Xiao, Wanyang; Lu, Weijie; Sun, Chenhui; Lou, Jietao; Xu, Yanyan; Chen, Tianbao; Wu, Di; Gao, Yitian","year":2025,"journal":"Toxins, 17(3)","doi":"10.3390/toxins17030114","pmid":"40137887","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14253","title":"Liraglutide Inhibits Autophagy to Ameliorate Post-Cardiac Arrest Brain Injury and Ferroptosis in Rats.","authors":"Xing, Chengjun; Fan, Xin; Liu, Mudi; Chen, Ye; Jia, Jing; Li, Wei; Yu, Hong; Zhou, Jun","year":2025,"journal":"Neurochemical research, 50(3), 161","doi":"10.1007/s11064-025-04412-z","pmid":"40349290","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14254","title":"Oxytocin and autism: Insights from clinical trials and animal models.","authors":"Xing, Chuan; Yu, Xiang","year":2025,"journal":"Current opinion in neurobiology, 92, 103015","doi":"10.1016/j.conb.2025.103015","pmid":"40157057","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review synthesizes three key lines of evidence linking oxytocin to autism: (1) reduced oxytocin levels and mutations in the oxytocin system have been documented in autism patients; (2) in animal models with oxytocin system deficits, social behavior problems mirror aspects of autism and can be rescued by administering oxytocin; and (3) clinical trials using intranasal oxytocin have shown some ability to alleviate social interaction deficits in autistic individuals.\n\nHowever, clinical outcomes have been inconsistent, suggesting that multiple factors influence treatment response. The neuropeptide's established roles — increasing attention to social cues, elevating salience of socially relevant stimuli, and enhancing social learning and reward — provide the mechanistic basis for its therapeutic potential in autism.","whyItMatters":"Autism spectrum disorder affects approximately 1 in 36 children in the US, and there are currently no medications that address core social interaction difficulties. If oxytocin-based therapies can be optimized — by identifying which patients respond best, determining optimal dosing, and understanding factors that influence outcomes — it could represent a breakthrough treatment targeting the fundamental social challenges of autism rather than just managing secondary symptoms.","specificNumbers":"","methodology":"This is a narrative review published in Current Opinion in Neurobiology that synthesizes findings from recent clinical trials of intranasal oxytocin in autistic individuals, alongside studies in animal models with oxytocin system deficits. The authors also reviewed the broader literature on oxytocin's roles in social behavior and its connection to autism etiology.","limitations":"As a narrative review, this study presents a selected synthesis rather than a systematic analysis of all available evidence. The abstract does not quantify response rates or effect sizes from the clinical trials reviewed. The translation from animal models to human clinical outcomes remains challenging given the complexity of human social behavior compared to rodent social paradigms. The heterogeneity of autism makes it difficult to draw universal conclusions."},{"rthcId":"RPEP-14255","title":"Dynamic Regulation of Macrophage Polarization in Acute Myocardial Infarction and Its Therapeutic Potential.","authors":"Xu, Anchen; Xu, Shuai; Tan, Xin; Sun, Qiaoyi; Song, Yahui; Nong, Yuxin; Wang, Xiangyu; Zeng, Yiyao; Fan, Huimin; Zhou, Yafeng","year":2025,"journal":"Journal of inflammation research, 18, 17363-17385","doi":"10.2147/JIR.S543139","pmid":"41416126","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14256","title":"Novel double-layered PLGA microparticles-dissolving microneedle (MPs-DMN) system for peptide drugs sustained release by transdermal delivery.","authors":"Xu, Bo; Liu, Han; Yang, Guozhong; Zhang, Suohui; Zhou, Zequan; Gao, Yunhua","year":2025,"journal":"International journal of pharmaceutics, 670, 125128","doi":"10.1016/j.ijpharm.2024.125128","pmid":"39722375","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14257","title":"Obstructive Sleep Apnea: An Evolving Therapeutic Landscape with an Emerging Role for Incretin-Based Therapies.","authors":"Xu, Bolong; Gaynor-Sodeifi, Kaveh; Kundel, Vaishnavi","year":2025,"journal":"Advances in therapy, 42(9), 4255-4269","doi":"10.1007/s12325-025-03312-6","pmid":"40699277","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14258","title":"A Sweet Almond Globulin Multifunctional Peptide: Identification, In Silico Screening, Restraint Mechanisms to Keap1 and ACE, and Antihypertensive and Ferrous Transport Efficiency.","authors":"Xu, Bufan; Long, Peiyao; Zheng, Yajun; Feng, Chen; Zhuang, Yongliang; Wu, Xinyi; Zheng, Siyin; Liu, Xinyu; Gao, Yiheng","year":2025,"journal":"Nutrients, 17(5)","doi":"10.3390/nu17050907","pmid":"40077777","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14259","title":"Semaglutide ameliorates retinal vascular permeability destruction in diabetic retinopathy by AnxA2-mediated MMP-9 activation and basement membrane remodeling.","authors":"Xu, Chengye; Meng, Ziyu; Lin, Wenjian; Li, Hongxue; Xu, Qian; Zhao, Kangqi; Chen, Yangwen; Wang, Yan; Zou, Wei; Kuang, Binglin; Kuang, Hongyu","year":2025,"journal":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 190, 118409","doi":"10.1016/j.biopha.2025.118409","pmid":"40749340","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14260","title":"Distal small bowel resection with preservation of the terminal ileum suppresses hepatic gluconeogenesis via the Prevotellaceae_NK3B31_group-mediated 7-KLCA-FXR axis.","authors":"Xu, Chi-Ying; Zheng, Zhi-Hua; Yang, Kun; Wu, Ren-Ran; Cao, Jia-Qing; Duan, Jin-Yuan","year":2025,"journal":"World journal of gastroenterology, 31(43), 112483","doi":"10.3748/wjg.v31.i43.112483","pmid":"41358181","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14261","title":"Reusability Report: Meta-Learning for Antigen-Specific T-Cell Receptor Binder Identification.","authors":"Xu, Dong; He, Fei; Wang, Xianyu","year":2025,"journal":"Research square","doi":"10.21203/rs.3.rs-7456773/v1","pmid":"41001547","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"PanPep's reported performance was successfully reproduced on original datasets. On a newly curated independent dataset, PanPep showed superior generalization to unseen antigens with few or no known TCR binders compared to control tools.\n\nThe framework was successfully extended to peptide-TCRα and peptide-TCRαβ binding prediction, demonstrating applicability in more biologically relevant contexts. However, PanPep showed limitations in early binder enrichment (identifying the top binders from large pools) and reduced robustness to novel TCRs not seen during training, indicating sensitivity to training data composition and negative sampling strategies.","whyItMatters":"Predicting which peptides will activate T cells is critical for developing cancer vaccines, infectious disease vaccines, and personalized immunotherapies. Current experimental methods are slow and expensive. AI tools like PanPep could dramatically accelerate this process, but they need to work reliably in real-world scenarios. This evaluation identifies both the promise and the gaps in current tools, guiding future development toward clinically useful prediction.","specificNumbers":"","methodology":"Comprehensive reusability evaluation of PanPep, a meta-learning framework for peptide-TCR binding prediction. Researchers reproduced reported performance on original datasets, benchmarked against control tools using classification metrics and virtual screening enrichment evaluations, tested on a newly curated independent dataset, and extended the framework to predict binding with TCRα and TCRαβ chains. A reproducible and extensible benchmarking framework was established.","limitations":"This is a computational benchmarking study without experimental validation of predictions. PanPep's limitations in early binder enrichment and novel TCR handling could significantly impact practical utility in screening scenarios. The evaluation used curated datasets that may not fully represent clinical diversity. The preprint status means the findings have not yet been peer-reviewed. Performance metrics may vary depending on the specific immunotherapy application."},{"rthcId":"RPEP-14262","title":"Self-assembled nanoparticle vaccine comprised of multiple epitopes provides robust protective immunity against reoviruses in fish model.","authors":"Xu, Fei-Fan; Zhao, Zhao; Deng, Zhu-Yang; Tang, Jia-Lun; Zhu, Bin","year":2025,"journal":"Cell communication and signaling : CCS, 23(1), 389","doi":"10.1186/s12964-025-02411-9","pmid":"40898220","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14263","title":"Design, Biological Characterization, and Discovery of Capromorelin Derivatives as Oral Growth Hormone Secretagogue Receptor Type 1a Agonist for the Treatment of Growth Hormone Deficiency.","authors":"Xu, Hang; Liu, Meng; Jia, Xiangyu; Zhao, Sheng; Xia, Yuanfeng; Lu, Biao; Yang, Fanglong; Wang, Siqin; Jin, Lei","year":2025,"journal":"Journal of medicinal chemistry, 68(6), 6766-6788","doi":"10.1021/acs.jmedchem.5c00217","pmid":"40091212","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Starting from capromorelin, researchers designed compound 4b, a novel oral ghrelin receptor (GHSR-1a) agonist with an EC50 of 0.49 nM — making it 100-fold more potent than ibutamoren (MK-677) at stimulating endogenous growth hormone release in rats. At oral doses as low as 0.1 mg/kg, compound 4b effectively triggered GH secretion. In young rats, 10 days of oral treatment increased both body weight and body length. In dogs, the compound showed 43.6% oral bioavailability with a 1.2-hour half-life.","whyItMatters":"Children with growth hormone deficiency currently require daily injections of recombinant growth hormone — a significant burden for young patients and their families. An oral pill that stimulates the body's own GH production could transform treatment. While MK-677 (ibutamoren) has been the most well-known oral GH secretagogue, compound 4b is 100 times more potent and showed actual growth effects in young animals, making it a more promising clinical candidate.","specificNumbers":"","methodology":"The researchers performed structure-activity relationship (SAR) optimization starting from capromorelin to design a series of derivatives. Compound 4b was evaluated for receptor binding potency (EC50 at GHSR-1a), oral pharmacokinetics in multiple species (rats and dogs), and in vivo GH release in rats. A 10-day oral dosing study in 4-week-old rats measured effects on body weight and length as indicators of growth stimulation.","limitations":"This is a preclinical study — no human data were collected. The 10-day growth study in rats is short, and longer-term efficacy, safety, and effects on IGF-1 levels and bone growth plates are unknown. The 1.2-hour half-life in dogs may require multiple daily doses. Potential side effects associated with GH secretagogues (appetite stimulation, insulin resistance, water retention) were not fully characterized."},{"rthcId":"RPEP-14264","title":"The Effect of Body Mass Index on the Efficacy of Semaglutide Use at the Time of Total Knee Arthroplasty.","authors":"Xu, Jacquelyn J; Johnson, Matthew C; Lama, Gabriel; Budin, Jacob S; Tabbaa, Ameer; Chen, Aaron Z; Magruder, Matthew L","year":2025,"journal":"The Journal of arthroplasty","doi":"10.1016/j.arth.2025.09.056","pmid":"41072554","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14265","title":"Proinflammatory Stress Activates Neutral Sphingomyelinase 2-Based Generation of a Ceramide-Enriched β-Cell EV Subpopulation.","authors":"Xu, Jerry; Amalaraj, Irene; De Oliveira, Andre; Harris-Kawano, Arianna; Enriquez, Jacob R; Mirmira, Raghavendra G; Eder, Josie G; Burnet, Meagan C; Díaz Ludovico, Ivo; Flores, Javier E; Nakayasu, Ernesto S; Sims, Emily K","year":2025,"journal":"Diabetes, 74(11), 1964-1975","doi":"10.2337/db24-0341","pmid":"40896819","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Inflammatory stress activated the enzyme nSMase2 in insulin-producing beta cells, generating ceramide-enriched extracellular vesicles (EVs) that carried distinct miRNA cargo linked to beta-cell function. These ceramide-loaded EVs impaired glucose-stimulated insulin secretion in neighboring healthy beta cells — an effect that was blocked when nSMase2 was knocked down in the parent cells. A GLP-1 receptor agonist was also able to modulate beta-cell EV ceramide content. Plasma EVs from children with recent-onset type 1 diabetes showed elevated ceramide species, confirming clinical relevance.","whyItMatters":"This research reveals a previously unknown mechanism by which stressed beta cells may spread dysfunction to their neighbors through ceramide-loaded vesicles. The finding that GLP-1 receptor agonists can modulate this process suggests a new dimension to how these peptide drugs protect beta cells — beyond their known effects on insulin secretion.","specificNumbers":"nSMase2-dependent pathway · ceramide-enriched EVs impaired insulin secretion · effect blocked by nSMase2 knockdown · elevated ceramide in T1D children's plasma EVs","methodology":"Combined in vitro and clinical approach: INS-1 beta cells and human islets were treated with proinflammatory cytokines; nSMase2 was modulated via chemical activation, genetic knockdown, and GLP-1 receptor agonist treatment. EV ceramide was profiled, RNA sequencing identified miRNA cargo, and functional assays measured insulin secretion in recipient cells. Plasma EVs from children with recent-onset type 1 diabetes were analyzed for ceramide content.","limitations":"The in vitro work used cell lines and isolated islets, which may not fully replicate in vivo beta-cell behavior. The clinical component (plasma EVs from T1D children) is observational and cannot establish causality. The specific GLP-1 receptor agonist dosing and its full mechanism of EV modulation require further study."},{"rthcId":"RPEP-14266","title":"Identification of a G Protein-Coupled Receptor for Buccalin-Type Peptides in the Mollusk Aplysia: Evolutionary Insights into Neuropeptide Signaling.","authors":"Xu, Ju-Ping; Ding, Xue-Ying; Jin, Qing-Chun; Zhang, Yi-Long; Chang, Jian-Hui; Jiang, Hui-Min; Li, Ya-Dong; Fu, Ping; Zhang, Yan-Chu-Fei; Liu, Cui-Ping; Mao, Rui-Ting; Liu, Cheng-Yi; Li, Fan; Wu, Shao-Qian; Cropper, Elizabeth C; Zhang, Guo; Jing, Jian","year":2025,"journal":"ACS omega, 10(39), 45073-45089","doi":"10.1021/acsomega.5c03789","pmid":"41078795","tags":["neuropeptides","receptor-identification","evolutionary-biology"],"studyType":"basic-research","evidenceStrength":"early-preclinical","keyFinding":"Researchers identified the first buccalin receptor in the sea slug Aplysia californica, designated apBuc/AstA-R. All 19 mature buccalin peptides activated this G protein-coupled receptor in a dose-dependent manner, with EC50 values ranging from 23 to 320 nM.\n\nCritically, the study found cross-activity: fruit fly allatostatin A peptides and human kisspeptin could also activate this Aplysia receptor, while human galanin could not. This supports the hypothesis that the mollusk buccalin/allatostatin A signaling system is evolutionarily related to the mammalian galanin and kisspeptin systems — peptide families important in reproduction, metabolism, and appetite.","whyItMatters":"Understanding how neuropeptide signaling systems evolved across species helps researchers trace the origins of peptides that are important in human health. Kisspeptin controls reproduction and galanin influences appetite and pain — knowing their evolutionary roots in ancient mollusk peptides could reveal conserved mechanisms and potential new drug targets.","specificNumbers":"19 buccalin peptides tested · EC50 range: 23–320 nM · Cross-activation by Drosophila AstA and human kisspeptin · No activation by human galanin","methodology":"The researchers used bioinformatics to identify candidate buccalin receptors in the Aplysia genome, then cloned the receptor and tested it in cell-based assays. They measured dose-response activation with all 19 buccalin peptides and tested cross-reactivity with fruit fly allatostatin A peptides and human kisspeptin and galanin. Phylogenetic and chromosomal analyses were used to map evolutionary relationships.","limitations":"This is a basic biology study in an invertebrate model (sea slug). The evolutionary connections to human kisspeptin and galanin systems, while supported by phylogenetic analysis, are inferred rather than functionally proven in mammalian systems. The KISSR-like receptor found in Aplysia could not be activated by any tested peptides, leaving its function unknown."},{"rthcId":"RPEP-14267","title":"Up-regulation of peripheral and central CGRP expression combined with subchondral bone remodeling in rat MIA-induced TMJOA model.","authors":"Xu, Liqin; Jiang, Henghua; Xu, Qijun; Fang, Wei","year":2025,"journal":"Journal of oral & facial pain and headache, 39(4), 218-226","doi":"10.22514/jofph.2025.078","pmid":"41436118","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14268","title":"Octanoic acid-rich diet alleviates breast cancer-induced bone pain via the acyl-ghrelin/NPY pathway.","authors":"Xu, Longjie; Hou, Lili; Cao, Chun; Li, Xiaohua","year":2025,"journal":"The Korean journal of pain, 38(2), 138-151","doi":"10.3344/kjp.24388","pmid":"40108771","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14269","title":"Exploring Conformational Transitions in Biased and Balanced Ligand Binding of GLP-1R.","authors":"Xu, Marc; Vogel, Horst; Yuan, Shuguang","year":2025,"journal":"Molecules (Basel, Switzerland), 30(15)","doi":"10.3390/molecules30153216","pmid":"40807391","tags":[],"studyType":"computational","evidenceStrength":"preliminary","keyFinding":"Using molecular dynamics simulations, researchers revealed how three different types of GLP-1 receptor agonists — a biased small molecule (CHU-128), a balanced small molecule (danuglipron), and a balanced peptide (Peptide 19) — each produce distinct structural changes in the receptor. Each ligand induced unique helix packing arrangements and conformational dynamics, explaining at the atomic level why different drugs activate different downstream signaling pathways from the same receptor.\n\nThe simulations showed that biased versus balanced agonists produce fundamentally different receptor shapes, which determines whether the receptor preferentially signals through G-proteins, β-arrestin, or both.","whyItMatters":"GLP-1 drugs like semaglutide and tirzepatide are blockbuster medications, but they all cause side effects partly because they activate multiple signaling pathways at once. Understanding exactly how different agonists reshape the GLP-1 receptor could enable scientists to design 'biased' drugs that activate only the pathways needed for therapeutic benefit (like blood sugar control) while avoiding those that cause nausea or other side effects. This study provides the atomic-level blueprint for that kind of rational drug design.","specificNumbers":"3 agonists compared · CHU-128 (biased small molecule) · danuglipron (balanced small molecule) · Peptide 19 (balanced peptide) · all-atom molecular dynamics simulations","methodology":"Computational study using all-atom molecular dynamics (MD) simulations. Researchers modeled the GLP-1 receptor in complex with three prototypical agonists representing different binding modes and signaling profiles. Simulations tracked how each ligand changes the receptor's three-dimensional structure over time, revealing the conformational dynamics that determine signaling pathway preference.","limitations":"Purely computational — no experimental validation of the predicted conformational states. MD simulations depend on the accuracy of force fields and starting structures. The simulated timescales may not capture all biologically relevant conformational changes. Real cellular environments with lipid membranes, G-proteins, and other partners add complexity not fully captured in simulation."},{"rthcId":"RPEP-14270","title":"CGRP-mediated neural addiction in tumor dynamic remodeling.","authors":"Xu, Miaochun; Yu, Yang; Cao, Canhui","year":2025,"journal":"Trends in cancer, 11(9), 834-838","doi":"10.1016/j.trecan.2025.07.004","pmid":"40769818","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CGRP (calcitonin gene-related peptide) is emerging as a key mediator of tumor-nerve crosstalk that drives cancer growth, suppresses anti-tumor immunity, and contributes to cancer-associated symptoms. The concept of 'CGRP-mediated neural addiction' describes how tumors hijack neural signaling through CGRP to remodel their microenvironment and sustain growth, positioning CGRP as a promising therapeutic target for disrupting tumor-nerve interactions.","whyItMatters":"While CGRP is well known in migraine treatment, its role in cancer is a rapidly emerging field. This perspective reveals that the same peptide targeted by migraine drugs may be exploited by tumors to grow, evade the immune system, and cause symptoms. Given that anti-CGRP drugs are already widely available and safe, this opens the possibility of repurposing migraine medications for cancer treatment — a paradigm-shifting concept.","specificNumbers":"Perspective article · CGRP identified as neural driver of tumor growth, immune suppression, and cancer symptoms · tumor-nerve interaction framework","methodology":"This is a perspective/commentary article published in Trends in Cancer that synthesizes emerging evidence on CGRP's role in tumor-nerve crosstalk. It presents the conceptual framework of 'CGRP-mediated neural addiction' in cancer biology.","limitations":"As a short perspective piece, it presents a conceptual framework rather than new experimental data. Much of the evidence for CGRP's role in cancer is still preclinical. The concept of 'neural addiction' in tumors is relatively new and requires further mechanistic validation across multiple cancer types."},{"rthcId":"RPEP-14271","title":"Dynamic interplay of neuroendocrine signaling and immuno-surveillance in tumor niche remodeling.","authors":"Xu, Nuo; Bian, Saiyan; Lyu, Pin; He, Xuyang; Zheng, Wenjie","year":2025,"journal":"Critical reviews in oncology/hematology, 216, 104958","doi":"10.1016/j.critrevonc.2025.104958","pmid":"40975450","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies multiple neuroimmune mechanisms in the tumor microenvironment: norepinephrine and cortisol modulate dendritic cell priming, NK cell cytotoxicity, CD8+ T-cell function, and myeloid polarization to create immunosuppression. Neuropeptides including CGRP contribute to immune evasion. Tumors drive their own neural innervation (tumor-associated neurogenesis), creating positive feedback loops. Therapeutic strategies discussed include β-adrenergic blockade, CGRP receptor antagonism, and inhibition of neurotrophic factors (NGF, BDNF). Combining immune checkpoint inhibitors with neuromodulation is proposed to overcome drug resistance.","whyItMatters":"Immune checkpoint inhibitors have revolutionized cancer treatment but work in less than half of patients. Understanding that the nervous system actively suppresses anti-tumor immunity reveals a major reason for treatment resistance — and opens new combination strategies. Several of the proposed interventions (beta-blockers, CGRP antagonists) already exist as approved drugs for other conditions, making clinical translation potentially rapid.","specificNumbers":"","methodology":"Critical review of published literature examining bidirectional neuroimmune interactions in the tumor immune microenvironment (TIME). Covers both how neural elements shape immune responses and how immune/tumor signals remodel neural circuits. Discusses preclinical and emerging clinical evidence for neuromodulatory cancer therapeutics.","limitations":"Most evidence for neuroimmune interactions in cancer comes from preclinical models. The complexity of the tumor microenvironment means that targeting individual neural pathways may have limited impact. Clinical data for combining neuromodulation with immune checkpoint inhibitors is still emerging. The review covers many pathways broadly rather than providing deep mechanistic analysis of each. Species differences in neuroimmune signaling may limit translational relevance of animal studies."},{"rthcId":"RPEP-14272","title":"Liraglutide improves senescence and ameliorating diabetic sarcopenia via the YAP-TAZ pathway.","authors":"Xu, Qian; Qiu, Xuan; Di, Hailing; Li, Zhongkang; Liu, Zanchao; Liu, Kuanzhi","year":2025,"journal":"Journal of diabetes and its complications, 39(3), 108975","doi":"10.1016/j.jdiacomp.2025.108975","pmid":"39987624","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14273","title":"Efficacy of Glucagon-Like Peptide-1 Receptor Agonists in Obese or Diabetic Patients With Obstructive Sleep Apnea Syndrome: A Meta-Analysis.","authors":"Xu, Shan; Li, Jin'e; Qiu, Jiajun; Zhang, Yuying; Yang, Shiqi; Liu, Jianping","year":2025,"journal":"Nutrition reviews","doi":"10.1093/nutrit/nuaf115","pmid":"40700548","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14274","title":"Lipid Nanoparticle-Mediated Targeted Delivery of MEGF10 siRNA to Astrocytes Reduced Synaptic Phagocytosis and Promoted Stroke Recovery in Mice.","authors":"Xu, Tongtong; Chang, Yan; Wang, Runyuan; Xu, Jingjing; Qian, Dongliang; Yao, Huaitong; Gan, Lin; Deng, Shiyu; Lian, Qianyuan; Ye, Jing; Li, Wanlu; Zhang, Zhijun; Yang, Guo-Yuan; An, Qingzhu; Wang, Jixian; Li, Jianfeng; Tang, Yaohui","year":2025,"journal":"ACS applied materials & interfaces, 17(42), 57936-57952","doi":"10.1021/acsami.5c13954","pmid":"41071927","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14275","title":"Efficacy of levosimendan for acute decompensated heart failure with preserved ejection fraction in the elderly: a single-center retrospective analysis.","authors":"Xu, Xiaohong; Lv, Fangchao; Xu, Chenkai; Lai, Xiuxiu","year":2025,"journal":"BMC cardiovascular disorders, 26(1), 1","doi":"10.1186/s12872-025-05224-3","pmid":"41299325","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14276","title":"Characterization of avian β-defensin genes in Galliformes reveals widespread evolutionary diversification and distinct evolutionary relationships with infection risk.","authors":"Xu, Xiaoqin; Jian, Yi; Huang, Lijing; Luo, Wei; Wu, Bangyuan; Feng, Shaohua; Zhou, Caiquan; Zhang, Long","year":2025,"journal":"BMC genomics, 26(1), 211","doi":"10.1186/s12864-025-11390-7","pmid":"40033205","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14277","title":"Diagnosis of Tuberculous Pericarditis in Zhejiang, China: A Diagnostic Prediction Model Based on LASSO Logistic Regression.","authors":"Xu, Xiaoqun; Liu, Xiao; Yang, Chao; Cai, Long; Liu, Libin; Chen, Tielong; Zhu, Houyong; Wei, Hui","year":2025,"journal":"Journal of inflammation research, 18, 4681-4693","doi":"10.2147/JIR.S504183","pmid":"40195957","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14278","title":"Development of Flow-NMR Spectroscopy for Real-Time Monitoring and Kinetics Studies of Biomolecules: Case Study of Liraglutide Oligomerization.","authors":"Xu, Xingjian; Dal Poggetto, Guilherme; Liang, Yingkai; Trigo-Mouriño, Pablo; Dormer, Peter G; Ji, Yining; Mattern, Keith A; McCoy, Mark A; Reibarkh, Mikhail; Gao, Qi","year":2025,"journal":"Analytical chemistry, 97(16), 8870-8879","doi":"10.1021/acs.analchem.4c06988","pmid":"40230214","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14279","title":"Genetically proxied glucagon-like peptide-1 receptor agonist is associated with risk of tubulo-interstitial nephritis: A network Mendelian randomization study.","authors":"Xu, Xu-Chun; Huang, Fang-Zhong; Ying, Jun; Zhang, Ting-Ting; Huang, Hua-Ying","year":2025,"journal":"Medicine, 104(38), e44742","doi":"10.1097/MD.0000000000044742","pmid":"40988251","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14280","title":"An angiotensin-converting enzyme inhibitory peptide (Val-Trp) from cauliflower by-products exerts an antihypertensive effect via the eNOS/NO/cGMP pathway.","authors":"Xu, Yang; Dou, Zishan; Liu, Jingli; Yahia, Zineb Ould; Chen, Wei","year":2025,"journal":"Food & function, 16(10), 4048-4060","doi":"10.1039/d4fo03181d","pmid":"40293781","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Oral administration of Val-Trp (VW) at 40 mg/kg effectively reduced both systolic and diastolic blood pressure in spontaneously hypertensive rats (SHRs). The peptide works through a dual mechanism: it directly inhibits ACE by binding to the enzyme's active pocket, and it activates the eNOS/NO/cGMP signaling pathway, which promotes nitric oxide production, increases cGMP, decreases intracellular calcium, and ultimately relaxes blood vessels.\n\nMolecular studies revealed that VW binds to ACE through a spontaneous exothermic process involving hydrogen bonding and hydrophobic interactions, causing structural changes in the enzyme that prevent its normal substrate from binding.","whyItMatters":"High blood pressure affects over a billion people worldwide, and many current medications come with side effects. Finding natural ACE-inhibitory peptides from food waste like cauliflower by-products offers a dual benefit: a potential source of blood pressure-lowering compounds with fewer side effects, and a way to add value to agricultural waste that would otherwise be discarded.","specificNumbers":"","methodology":"Researchers tested the peptide VW in spontaneously hypertensive rats (SHRs) using oral administration at 40 mg/kg. They used a cell model with human umbilical vein endothelial cells (HUVECs) stimulated by angiotensin I to study the mechanism. Isothermal titration calorimetry measured VW-ACE binding, fluorescence spectroscopy tracked enzyme structural changes, and molecular docking modeled how VW fits into ACE's active site.","limitations":"The study was conducted in rats, not humans, so the blood pressure-lowering effects may not translate directly to people. The specific dosing (40 mg/kg) would need to be validated in human trials. The study did not assess long-term safety, bioavailability after digestion, or how the peptide compares to existing antihypertensive drugs in efficacy."},{"rthcId":"RPEP-14281","title":"Design and Biosynthesis of Ornithine 8-Containing Semaglutide Variants with a Click Chemistry-Modifiable Position 26.","authors":"Xu, Yanli; Kuipers, Oscar P","year":2025,"journal":"ACS synthetic biology, 14(5), 1790-1801","doi":"10.1021/acssynbio.5c00132","pmid":"40305415","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14282","title":"Targeting Antigen-Presenting Cells to Enhance the Tumor-Spleen Immunity Cycle through Liposome-Neoantigen Vaccine.","authors":"Xu, Yu; Wang, Bing; Huang, Yue; Liao, JianPing; Wu, Chenyi; Zhou, Chenxi; Kang, Zishi; Jiang, Shiyang; Wu, Bing-Chen; Zhang, Da; Xu, Ruihua; Liu, Xiaolong; Wang, Feng","year":2025,"journal":"Advanced science (Weinheim, Baden-Wurttemberg, Germany), 12(19), e2500021","doi":"10.1002/advs.202500021","pmid":"40125791","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14283","title":"Exploring the potential pathogenesis of migraine using glutamatergic neuron models derived from induced pluripotent stem cells (iPSCs) of migraine patients.","authors":"Xu, Yueyue; Yao, Yitian; Sun, Li; Chen, Li; Li, Chenyang; Wang, Wenyuan; Yang, Jiajun","year":2025,"journal":"Brain research, 1866, 149938","doi":"10.1016/j.brainres.2025.149938","pmid":"40930453","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Glutamatergic neurons derived from migraine patient iPSCs showed functional abnormalities compared to healthy controls. Ion channel dysfunction was observed in sodium and potassium channel function via patch-clamp recordings. Expression of migraine-associated molecules was altered, including CGRP (calcitonin gene-related peptide), P2RX3 (a pain receptor), and c-Fos (a marker of neuronal activation).\n\nThese findings collectively suggest that intrinsic neuronal dysfunction — present even in lab-grown cells outside the body — may contribute to migraine pathology. The study establishes the feasibility of using iPSC-derived neurons as a human-specific migraine research model.","whyItMatters":"Current migraine research relies heavily on animal models that can't capture the human-specific genetics and biology driving migraines. This iPSC approach creates neurons that carry the patient's actual genetic background, enabling researchers to study migraine mechanisms in a way that's directly relevant to the human disease. The finding that CGRP — the target of today's most effective migraine drugs — is abnormally expressed in these patient-derived neurons validates the model and could eventually enable testing of personalized treatments.","specificNumbers":"","methodology":"Induced pluripotent stem cells (iPSCs) were generated from both migraine patients and healthy controls, then differentiated into glutamatergic neurons. Electrophysiological properties were measured using whole-cell patch-clamp recordings to assess sodium and potassium channel function. Expression of migraine-associated molecules (CGRP, P2RX3, c-Fos) was evaluated using immunofluorescence staining and quantitative real-time PCR.","limitations":"This is a proof-of-concept study with preliminary findings. The abstract does not specify the number of patient and control iPSC lines used, which is critical for a field prone to line-to-line variability. iPSC-derived neurons may not fully recapitulate the complexity of neurons in the intact brain, including their connections with other cell types and the trigeminal vascular system central to migraine. The in vitro environment lacks the hormonal, vascular, and immune system influences that contribute to migraine attacks."},{"rthcId":"RPEP-14284","title":"Titration and discontinuation of semaglutide for weight management in commercially insured US adults.","authors":"Xu, Yunwen; Carrero, Juan J; Chang, Alexander R; Inker, Lesley A; Zhang, Donglan; Mukhopadhyay, Amrita; Blecker, Saul B; Horwitz, Leora I; Grams, Morgan E; Shin, Jung-Im","year":2025,"journal":"Obesity (Silver Spring, Md.), 33(7), 1243-1248","doi":"10.1002/oby.24315","pmid":"40464214","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 15,811 commercially insured adults who started semaglutide for weight management, 46% discontinued within the first 5 months. Discontinuation was strongly linked to out-of-pocket costs: rates ranged from 41% in the lowest copayment quintile ($1-$54/month) to 51% in the highest quintile ($161-$1,460/month). Most users deviated from the recommended monthly dose-escalation schedule. Similar discontinuation rates (48%) were observed in patients starting after supply shortages resolved (post-October 2023), indicating the problem is not supply-driven.","whyItMatters":"GLP-1 peptide drugs like semaglutide require ongoing use to maintain weight loss — stopping typically leads to weight regain. With nearly half of real-world users quitting within 5 months, the actual public health impact of these drugs may be far less than clinical trial results suggest. The strong association with cost highlights that access, not just efficacy, is the critical challenge for peptide-based obesity therapies.","specificNumbers":"","methodology":"Retrospective cohort study using insurance claims data for 15,811 commercially insured US adults who initiated semaglutide for weight management (single-dose prefilled pens) between June 2021 and December 2023. Dose-titration patterns were tracked over 5 months. Multivariable Cox regression identified factors associated with discontinuation. Sensitivity analyses examined patterns after supply shortage resolution.","limitations":"The study used insurance claims data, which cannot capture reasons for discontinuation beyond cost (e.g., side effects, inadequate response, personal choice). It included only commercially insured adults, so patterns may differ for Medicare, Medicaid, or uninsured populations. The 5-month follow-up is relatively short for a chronic therapy. Dose-titration deviations could reflect supply shortages during part of the study period, though sensitivity analysis after shortage resolution showed similar patterns."},{"rthcId":"RPEP-14285","title":"Phosvitin-Derived Peptide Pt5-1c Is a Pro-Angiogenic Agent Capable of Enhancing Wound Healing.","authors":"Xuan, Cuiling; Li, Mei; Zhang, Peng; Wang, Yunchao; Li, Hongyan; Gao, Zhiqin; Zhang, Shicui; Wu, Fei","year":2025,"journal":"Biomolecules, 16(1)","doi":"10.3390/biom16010065","pmid":"41594605","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The fish phosvitin-derived antimicrobial peptide Pt5-1c enhanced angiogenesis (new blood vessel formation) in both murine full-thickness wound models and zebrafish vascular defect models. In vitro, Pt5-1c promoted endothelial cell motility, adhesion, survival, filopodia protrusion, and tube formation. It upregulated proangiogenic growth factors VEGF, PDGF, FGF, and EGF. The signaling pathways involved were PI3K/AKT/mTOR, p38 MAPK, and HIF-1-VEGF axis.","whyItMatters":"Chronic wounds — diabetic ulcers, pressure sores, and non-healing surgical wounds — affect millions of people and often fail to heal due to inadequate blood vessel formation. Finding that an antimicrobial peptide can simultaneously fight infection AND promote new blood vessel growth addresses both key challenges in wound healing with a single agent.","specificNumbers":"Wound healing improved in mouse full-thickness wounds · vascular defects rescued in zebrafish · VEGF, PDGF, FGF, EGF upregulated · PI3K/AKT/mTOR and p38 MAPK pathways activated","methodology":"Combined in vitro and in vivo study. In vitro: human umbilical vein endothelial cells tested for motility, adhesion, survival, filopodia formation, and tube formation. Growth factor expression measured. In vivo: murine full-thickness wound healing model and zebrafish vascular defect model assessed angiogenic effects. Signaling pathway analysis identified PI3K/AKT/mTOR and p38 MAPK involvement.","limitations":"Preclinical study using animal wound models that may not fully replicate human chronic wound biology. The specific peptide dose, treatment schedule, and wound closure rates are not detailed in the abstract. Long-term safety and potential immunogenicity of the fish-derived peptide in mammals were not assessed."},{"rthcId":"RPEP-14286","title":"Design of Entry Inhibitor Peptides Covalently Bonding SARS-CoV-2 Variants in Wastewater.","authors":"Xue, Boyuan; Li, Ruixue; Zhu, Qian; Yang, Yihan; Wang, Fan; Cheng, Zhao; Zhou, Xiaohong","year":2025,"journal":"Environmental science & technology, 59(18), 9146-9154","doi":"10.1021/acs.est.5c02307","pmid":"40293255","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14287","title":"Predicting prognosis using stroke-heart indicator: brain natriuretic peptide in patients with aneurysmal subarachnoid hemorrhage.","authors":"Xue, Jionghao; Lin, Fa; Liu, Minghao; Song, Wenxiong; Li, Runting; Chen, Yu; Yang, Jun; Han, Heze; Jia, Yitong; Chen, Xiaolin; Wang, Rong; Zhao, Yuanli","year":2025,"journal":"Frontiers in neurology, 16, 1510235","doi":"10.3389/fneur.2025.1510235","pmid":"39911457","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14288","title":"State-Specific Peptide Design Targeting G Protein-Coupled Receptors.","authors":"Xue, Yang; Wang, Hong; Li, Jun; Hu, Jianguo; Chen, Zhiyuan; Zheng, Zhi; Liu, Lihang; Zhu, Kunrui; He, Jingzhou; Gong, Huanzhang; Li, Xiangqun; Zhang, Xiaonan; Fang, Xiaomin","year":2025,"journal":"Journal of chemical information and modeling, 65(20), 11425-11438","doi":"10.1021/acs.jcim.5c00884","pmid":"41074841","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14289","title":"Antimicrobial peptide delivery to lung as peptibody mRNA in anti-inflammatory lipids treats multidrug-resistant bacterial pneumonia.","authors":"Xue, Yonger; Hou, Xucheng; Wang, Siyu; Zhang, Yuebao; Zhong, Yichen; Kang, Diana D; Wang, Chang; Li, Haoyuan; Yu, Changyue; Liu, Zhengwei; Tian, Meng; Cao, Dinglingge; Zheng, Ya Ying; Deng, Binbin; Hamon, Pauline; Merad, Miriam; Dong, Yizhou","year":2025,"journal":"Nature biotechnology","doi":"10.1038/s41587-025-02928-x","pmid":"41299045","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14290","title":"Combined metformin and exenatide versus only metformin treatments in polycystic ovary syndrome with abdominal obesity and network pharmacology of gene expression: evidence from a randomized clinical trial.","authors":"Xuesong, Ding; Tao, Tao; Weilu, Wang; Wei, Xiong; Wei, Xue; Yan, Deng; Yanfang, Wang; Ruilin, Ma; Yingying, Guo; Yue, Wang; Pérez-López, Faustino R; Yang, Wang","year":2025,"journal":"Therapeutic advances in endocrinology and metabolism, 16, 20420188251355411","doi":"10.1177/20420188251355411","pmid":"40843067","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14291","title":"A multicenter, prospective, real-world study of oral semaglutide in adults with type 2 diabetes in Japanese clinical practice (PIONEER REAL Japan): Subgroup analyses.","authors":"Yabe, Daisuke; Hamamoto, Yoshiyuki; Kawanami, Daiji; Nishimura, Rimei; Terauchi, Yasuo; Amadid, Hanan; Braae, Uffe Christian; Major-Pedersen, Atheline; Suzuki, Ryo","year":2025,"journal":"Journal of diabetes investigation, 16(10), 1794-1807","doi":"10.1111/jdi.70099","pmid":"40711887","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14292","title":"GLP-1 and ghrelin inversely regulate insulin secretion and action in pancreatic islets, vagal afferents, and hypothalamus for controlling glycemia and feeding.","authors":"Yada, Toshihiko; Dezaki, Katsuya; Iwasaki, Yusaku","year":2025,"journal":"American journal of physiology. Cell physiology, 328(6), C1793-C1807","doi":"10.1152/ajpcell.00168.2025","pmid":"40241252","tags":["glp-1-agonists","ghrelin"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"GLP-1 and ghrelin act as opposing regulators of the insulin system at three key levels: pancreatic beta cells (GLP-1 stimulates insulin release, ghrelin suppresses it), vagal afferent neurons, and hypothalamic arcuate nucleus neurons. Critically, their timing is complementary — ghrelin rises and acts before meals while GLP-1 rises and acts after meals. This preprandial/postprandial interplay with insulin creates an integrated circadian control system for appetite, blood sugar, and metabolism.","whyItMatters":"Understanding how GLP-1 and ghrelin work together — not just individually — explains why drugs targeting either hormone can have such broad metabolic effects. It also suggests that future therapies manipulating both pathways simultaneously could achieve more precise control of appetite and blood sugar.","specificNumbers":"","methodology":"Narrative review integrating evidence from cellular studies in pancreatic beta cells, neurophysiology of vagal afferents and hypothalamic arcuate nucleus neurons, and hormonal signaling research across animal and human studies.","limitations":"As a review, this synthesizes existing research rather than presenting new data. Much of the mechanistic detail comes from animal models (particularly mice). The described interplay between GLP-1, ghrelin, and insulin is a framework for understanding, not a complete model — other hormones and neural pathways also participate."},{"rthcId":"RPEP-14293","title":"Neuroprotective and cognitive benefits of Semaglutide: Insights into the underlying molecular mechanisms.","authors":"Yaghmayee, Shayan; Moazzeni, Atefeh Sadat; Jamialahmadi, Tannaz; Karav, Sercan; Yaribeygi, Habib; Kesharwani, Prashant; Sahebkar, Amirhossein","year":2025,"journal":"Neuroscience, 579, 187-197","doi":"10.1016/j.neuroscience.2025.06.009","pmid":"40494410","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14294","title":"B-type natriuretic peptide efficacy compared to fragmented QRS for diastolic dysfunction screening in patients with type 2 diabetes.","authors":"Yagi, Kunimasa; Chujo, Daisuke; Usui, Isao; Liu, Jian-Hui; Nohara, Atsushi; Shirozu, Asako Enkaku; Takikawa, Akiko; Honoki, Hisae; Fujisaka, Shiho; Origasa, Hideki; Tada, Hayato","year":2025,"journal":"World journal of diabetes, 16(4), 103551","doi":"10.4239/wjd.v16.i4.103551","pmid":"40236863","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14295","title":"Structural and mechanistic divergence in LL-37, HNP-1, and Magainin-2: An integrated computational and biophysical analysis.","authors":"Yakobi, Sinethemba H; Nwodo, Uchechukwu U","year":2025,"journal":"Current research in structural biology, 10, 100176","doi":"10.1016/j.crstbi.2025.100176","pmid":"41376844","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14296","title":"Impact of Glucagon-like Peptide-1 Receptor Agonists on Metabolic Health in Liver Transplant Recipients.","authors":"Yakubu, Idris; Spengler, Joseph; Taylor, Perry; LaPorte, Michael; Brown, Andrew; Sterling, Sara; Agegnehu, Bem; Iaria, Aoife; Marks, Ryan; Sprague, Taylor; Pontinha, Vasco; Patel, Vaishali; Patidar, Kavish R; Siddiqui, Mohammad Shadab","year":2025,"journal":"Transplantation, 109(9), e501-e507","doi":"10.1097/TP.0000000000005361","pmid":"40128152","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14297","title":"Pharmacogenetics of incretin-based therapies.","authors":"Yaluri, Alena Stančáková; Ürgeová, Anna; Maršálek, Michal; Javorský, Martin; Tkáč, Ivan","year":2025,"journal":"Postgraduate medical journal","doi":"10.1093/postmj/qgaf232","pmid":"41474140","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14298","title":"Neuropeptide Y neurons in the basolateral amygdala project to the nucleus accumbens and stimulate high-fat intake.","authors":"Yamada, Shunji; Kojima, Kazunori; Tanaka, Masaki","year":2025,"journal":"Frontiers in cellular neuroscience, 19, 1565939","doi":"10.3389/fncel.2025.1565939","pmid":"40213497","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14299","title":"Quantitative Analysis of Neuropeptide Y (NPY) and C-Terminal Glycine-Extended NPY by Mass Spectrometry and Their Localization in the Developing and Sexual Adult Mouse Brains.","authors":"Yamagaki, Tohru; Osugi, Tomohiro; Shinmyo, Yohei; Kawasaki, Hiroshi; Satake, Honoo","year":2025,"journal":"ACS chemical neuroscience, 16(4), 588-594","doi":"10.1021/acschemneuro.4c00545","pmid":"39899812","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14300","title":"Early induction of insulin sensitisation treated by tirzepatide: a prospective, single-arm, open-label study in Japanese individuals with obesity and type 2 diabetes.","authors":"Yamaguchi, Yuko; Kuwata, Hitoshi; Imura, Masahiro; Moyama, Shota; Usui, Ryota; Matsushiro, Mari; Hamamoto, Yoshiyuki; Yamada, Yuichiro; Seino, Yutaka; Yamazaki, Yuji","year":2025,"journal":"Diabetologia, 68(10), 2151-2155","doi":"10.1007/s00125-025-06493-5","pmid":"40694059","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 16 participants who completed the 12-week study, the glucose infusion rate (GIR, the gold standard measure of insulin sensitivity) increased from 3.21 to 5.16 mg/min/kg — a 61% improvement (p significant). HbA1c decreased from 63.4 to 43.6 mmol/mol (7.95% to 6.14%, p < 0.001). Body weight decreased by 4.9 kg (5.0%, p < 0.001). Fat mass decreased by 9.1%, muscle mass by 1.8%, and fat percentage by 4.5%. Glucagon decreased from 28.8 to 20.8 pg/ml.\n\nCritically, simple linear regression showed no significant relationship between changes in GIR and changes in any other clinical variable, indicating that the insulin sensitivity improvement was not explained by weight loss, fat reduction, or other measurable metabolic changes alone.","whyItMatters":"Most GLP-1-class drugs are assumed to improve metabolic health primarily through weight loss. This study challenges that assumption by using the most rigorous insulin sensitivity measurement available and showing that tirzepatide's metabolic benefits occur rapidly and independently of weight change. This has major implications for understanding how tirzepatide works and for patients who may benefit from improved insulin sensitivity even before significant weight loss occurs.","specificNumbers":"","methodology":"Prospective, single-arm, open-label, single-center study in obese Japanese patients with type 2 diabetes. Participants received tirzepatide 2.5 mg weekly for 4 weeks, then 5 mg for 8 weeks. Insulin sensitivity was measured using the hyperinsulinemic-euglycemic clamp technique (gold standard) before and after treatment. Body composition was assessed. Secondary outcomes included HbA1c, body weight, lipid profile, glucagon, and HOMA indices. Registered: UMIN000056862.","limitations":"This was a very small (n=16), single-arm, open-label study without a control group, so improvements cannot be definitively attributed to tirzepatide alone. The study used only the low dose (5 mg), and results may differ at higher doses. The 12-week duration is short, and longer-term insulin sensitivity changes may differ. The exclusively Japanese cohort limits generalizability to other populations. The lack of a comparator arm (e.g., GLP-1 agonist alone) means the contribution of the GIP component cannot be isolated."},{"rthcId":"RPEP-14301","title":"Evaluation of the Short-Term Effect of Tirzepatide on Liver Fibrosis Biomarkers Stratified by the Fibrosis-3 Index (FIB-3) in Patients With Type 2 Diabetes Mellitus.","authors":"Yamamori, Daichi; Kitao, Takashi; Masuda, Sachiko; Koike, Shimpei; Kaketaka, Tomoko; Komoda, Yoshio; Nakano, Erico; Konishi, Eriko; Ibata, Takeshi","year":2025,"journal":"Cureus, 17(11), e97279","doi":"10.7759/cureus.97279","pmid":"41431568","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14302","title":"Extracellular processing of proopiomelanocortin generates short beta endorphin that regulates rat keratinocytes via the delta opioid receptor.","authors":"Yamamoto, Hiroyuki; Sawaguchi, Yoshikazu; Koida, Ayaka; Yamada, Toshiyuki","year":2025,"journal":"Scientific reports, 16(1), 1734","doi":"10.1038/s41598-025-31279-5","pmid":"41381767","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14303","title":"Physiology and clinical applications of GIP.","authors":"Yamane, Shunsuke; Harada, Norio; Inagaki, Nobuya","year":2025,"journal":"Endocrine journal, 72(7), 751-764","doi":"10.1507/endocrj.EJ25-0087","pmid":"40175127","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14304","title":"The Roles of Incretin Hormones GIP and GLP-1 in Metabolic and Cardiovascular Health: A Comprehensive Review.","authors":"Yamanouchi, Dai","year":2025,"journal":"International journal of molecular sciences, 27(1)","doi":"10.3390/ijms27010027","pmid":"41515907","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Dual GIP/GLP-1 receptor agonists, led by tirzepatide, provide superior glycemic control and weight loss compared to selective GLP-1 receptor agonists alone, demonstrating synergistic effects between the two incretin pathways. GIP, historically overlooked due to reduced beta-cell responsiveness in type 2 diabetes, has been rehabilitated as a therapeutic target through dual agonism.\n\nThe review identifies multiple cardiovascular protective mechanisms of incretin hormones: improved lipid metabolism, blood pressure reduction, enhanced endothelial nitric oxide activity, suppressed macrophage inflammation, decreased foam-cell formation, and atherosclerotic plaque stabilization. Emerging triple agonists and genotype-guided incretin therapy represent the next frontier.","whyItMatters":"The shift from single GLP-1 agonists to dual and triple incretin agonists represents a paradigm change in metabolic medicine. Understanding how GIP and GLP-1 work together — not just for blood sugar and weight, but also for cardiovascular protection — reshapes how we think about treating the interconnected diseases of diabetes, obesity, and heart disease as a unified metabolic syndrome.","specificNumbers":"2 incretin hormones (GIP + GLP-1) · Tirzepatide first-in-class dual agonist · Superior to selective GLP-1RAs · Multiple CV protective mechanisms · Triple agonists in development","methodology":"Comprehensive narrative review covering incretin biology from basic physiology through clinical therapeutics. Synthesizes evidence on secretion patterns, receptor distributions, pathophysiology in diabetes and obesity, cardiovascular mechanisms, and emerging therapeutic approaches.","limitations":"As a narrative review, this does not provide systematic evidence grading or pooled analysis. Long-term cardiovascular effects of GIP specifically remain unresolved. The review acknowledges that genotype-guided incretin therapy is still speculative."},{"rthcId":"RPEP-14305","title":"Reference values for cardiac hormones in young Japanese macaques (Macaca fuscat).","authors":"Yamaoka, Arao; Nakayama, Shunya; Ito-Fujishiro, Yasuyo; Yoneda, Ibuki; Kinoshita, Rie; Koie, Hiroshi","year":2025,"journal":"The Journal of veterinary medical science, 87(4), 377-383","doi":"10.1292/jvms.24-0446","pmid":"39956610","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14306","title":"Comparative analysis of bone regeneration in critical-sized defects using self-assembling peptide hydrogel-178, bone morphogenetic protein-2, and calcium phosphate scaffolds in a rat femur model.","authors":"Yamauchi, Ippei; Nakashima, Hiroaki; Ito, Sadayuki; Segi, Naoki; Ouchida, Jun; Morita, Yoshinori; Ode, Yukihito; Nagatani, Yasuhiro; Okada, Yuya; Ando, Kei; Imagama, Shiro","year":2025,"journal":"Nagoya journal of medical science, 87(3), 421-430","doi":"10.18999/nagjms.87.3.421","pmid":"41140815","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Self-assembling peptide hydrogel (0.8%) produced a bone-volume-to-total-volume (BV/TV) ratio of 0.34 ± 0.09 at 56 weeks, which was not significantly higher than the empty control cage. BMP-2 (50 ng/μL) with bone chips achieved the highest BV/TV ratio of 0.78 ± 0.05, significantly exceeding bone chips alone (p<0.01) and peptide hydrogel with bone chips (p<0.05). The results indicate that peptide hydrogels benefit from combination with osteoinductive factors like BMP-2.","whyItMatters":"Large bone defects from trauma, tumor removal, or infection remain a major surgical challenge. Self-assembling peptide hydrogels are attractive because they're injectable and can be used in minimally invasive procedures. Understanding that they need to be combined with growth factors like BMP-2 guides their clinical development toward combination products rather than standalone use.","specificNumbers":"","methodology":"Ten-week-old female Wistar rats received 5-mm femoral mid-shaft defects stabilized with external fixators and filled with PEEK cages containing various materials. Two experiments were performed: materials alone, then materials combined with bone chips. Bone formation was assessed at 56 weeks by radiographic and histological analysis with BV/TV ratio quantification.","limitations":"This is a rat model, and bone healing differs between rats and humans. The 56-week timeline is exceptionally long for a rat study but still represents preclinical data. The peptide hydrogel concentration (0.8%) and BMP-2 dose (50 ng/μL) represent specific formulations that may not be optimal. Small group sizes typical of these surgical models limit statistical power."},{"rthcId":"RPEP-14307","title":"Efficacy and safety of once-weekly tirzepatide in Japanese participants with type 2 diabetes who have obesity or overweight: Subpopulation analysis of the SURMOUNT-2 trial.","authors":"Yamauchi, Toshimasa; Asakura, Taro; Shingaki, Tomotaka; Oura, Tomonori; Katagiri, Hideki","year":2025,"journal":"Diabetes, obesity & metabolism, 27(8), 4557-4566","doi":"10.1111/dom.16500","pmid":"40490415","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14308","title":"Exploring Predictors of Treatment Response to GLP-1 Receptor Agonists for Smoking Cessation.","authors":"Yammine, Luba; de Dios, Constanza; Suchting, Robert; Green, Charles E; Nielsen, David A; Walss-Bass, Consuelo; Schmitz, Joy M","year":2025,"journal":"Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco, 27(7), 1294-1300","doi":"10.1093/ntr/ntaf005","pmid":"39780397","tags":[],"studyType":"Secondary Analysis of Randomized Controlled Trial","evidenceStrength":"moderate","keyFinding":"In a secondary analysis of a pilot RCT, the GLP-1 agonist exenatide showed stronger smoking cessation benefits in specific patient subgroups. Exenatide (added to nicotine patch) worked better than placebo plus nicotine patch in people who smoked more than 20 cigarettes per day (posterior probability 81.7%), those without obesity (PP = 94.4%), those without prediabetes (PP = 76.0%), and those with no or minimal depression (PP = 91.2%).\n\nA striking genetic finding emerged: exenatide was more effective only in individuals with the CHRNA rs16969968 GG genotype (PP = 88.6%), a nicotine receptor gene variant associated with smoking behavior. This suggests that GLP-1 drugs for smoking cessation may be most effective in a specific subset of smokers — heavy smokers who are not obese, not depressed, and carry a particular genetic profile.","whyItMatters":"The idea that GLP-1 drugs could help people quit smoking is one of the most exciting emerging applications of these peptides. But not everyone may benefit equally. This study is among the first to identify who responds best to GLP-1 treatment for smoking cessation, potentially enabling precision medicine approaches. The finding that metabolic health, depression status, and genetics all predict response suggests the mechanism involves more than just appetite suppression.","specificNumbers":"n=84 · Exenatide 2 mg SC once weekly + nicotine patch 21 mg · Stronger in >20 cig/day (PP=81.7%) · Stronger without obesity (PP=94.4%) · Only effective with minimal depression (PP=91.2%) · CHRNA rs16969968 GG genotype (PP=88.6%)","methodology":"Secondary analysis of a randomized, placebo-controlled pilot trial. 84 smokers with prediabetes and/or overweight were randomized 1:1 to once-weekly exenatide 2 mg or placebo, both with nicotine patch (21 mg) and counseling. The primary outcome was biologically confirmed 7-day point prevalence abstinence at week 6. Bayesian generalized linear modeling was used to explore how baseline demographics, clinical factors, smoking intensity, psychosocial measures, and genetic variants moderated treatment response.","limitations":"This is a secondary (post-hoc) analysis of a small pilot trial with only 84 participants — subgroup analyses with this sample size should be considered hypothesis-generating, not definitive. Bayesian posterior probabilities ≥75% were used as thresholds, which is less stringent than conventional significance testing. Multiple subgroup comparisons increase the risk of finding spurious associations. The parent trial used exenatide (an older GLP-1 agonist), not semaglutide or tirzepatide."},{"rthcId":"RPEP-14309","title":"The Potential Utility of GLP-1 Receptor Agonist Medications for Addiction Treatment: A Narrative Review of Clinical and Epidemiological Evidence.","authors":"Yammine, Luba; Grigson, Patricia Sue; Schmitz, Joy M; Evans, Brianna B; Hendershot, Christian S","year":2025,"journal":"Current addiction reports, 12","doi":"10.1007/s40429-025-00657-4","pmid":"41347181","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14310","title":"Perioperative Use of Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists Lower Readmission Rates After Coronary Artery Bypass Grafting (CABG) in Adults With Congenital Heart Disease.","authors":"Yan, Jason H; McKinnerney, Joey; Al Janabi, Taysir; Chahal, Anwar; Malik, Adnan; Vranian, Michael N; Kashyap, Rahul","year":2025,"journal":"Cureus, 17(10), e95767","doi":"10.7759/cureus.95767","pmid":"41322791","tags":[],"studyType":"Retrospective Cohort Study","evidenceStrength":"moderate","keyFinding":"In adult congenital heart disease (CHD) patients who underwent coronary artery bypass grafting (CABG), perioperative use of GLP-1 receptor agonists was associated with a 32% reduction in one-year hospital readmission rates (OR = 0.68, p = 0.0118) compared to non-users after propensity score matching.\n\nImportantly, GLP-1 RA use did not increase mortality (OR = 0.747, p = 0.35), nor did it increase rates of any postoperative complications including acute kidney injury, heart attack, stroke, or arrhythmia. Known GLP-1-related side effects like gastroparesis and abnormal weight loss showed no difference between groups. The study suggests GLP-1 agonists are safe to use around heart bypass surgery and may reduce the likelihood of hospital readmission.","whyItMatters":"GLP-1 receptor agonists are widely prescribed for diabetes and obesity, but surgeons and anesthesiologists have been cautious about their use around surgery due to concerns about gastroparesis and aspiration risk. This study provides reassuring evidence that these drugs don't increase surgical complications and may actually improve outcomes by reducing readmissions in a high-risk cardiac population.","specificNumbers":"n=720 (360 per group) · 32% lower readmission rate (OR=0.68, p=0.0118) · No mortality difference (OR=0.747, p=0.35) · No increase in GLP-1-related complications · 2005-2025 data","methodology":"Retrospective cohort study using de-identified patient data from the TriNetX Research Network (2005-2025). Adult CHD patients who underwent CABG were divided into GLP-1 RA users (within 3 months before or 1 month after surgery) and non-users. Propensity score matching (1:1) balanced 360 patients per group on demographics, comorbidities, and CHD diagnoses. Outcomes measured at one year included mortality, readmission, postoperative events, and GLP-1-related complications.","limitations":"Retrospective design cannot establish causation — the readmission benefit could reflect healthier patients or better overall care. TriNetX database studies rely on billing codes, which may miss undocumented drug use or misclassify diagnoses. The GLP-1 RA group likely included patients with diabetes or obesity (indications for the drug), which despite matching could introduce residual confounding. Published in Cureus, which has a less rigorous peer review process."},{"rthcId":"RPEP-14311","title":"T cell receptor mimic CAR T cells targeting cathepsin G signal peptide.","authors":"Yan, Jun; Shi, Chunhua; Yang, Guojun; Tian, Ze; Torikai, Hiroki; Sukhumalchandra, Pariya; Peng, Shaohua; Chang, Edward; Cui, Meng; Kerros, Celine; Philips, Anne; Qiao, Na; Zhang, Mao; Lofton, Timothy E; Allen, Jason K; Gonzalez, Michelle A; Patchametla, Sathvik; Sergeeva, Anna; St John, Lisa; He, Helen; Zha, Dongxing; Molldrem, Jeffrey; Alatrash, Gheath","year":2025,"journal":"Leukemia, 39(8), 1948-1959","doi":"10.1038/s41375-025-02652-0","pmid":"40437170","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14312","title":"Beyond GLP-1: efficacy and safety of dual and triple incretin agonists in personalized type 2 diabetes care-a systematic review and network meta-analysis.","authors":"Yan, Kangling; Yu, Haichuan; Blaise, Benoît","year":2025,"journal":"Acta diabetologica, 62(9), 1359-1370","doi":"10.1007/s00592-025-02534-y","pmid":"40471293","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14313","title":"L009 peptide as a novel antiangiogenic agent for corneal neovascularization via regulation of the TNFSF15-VEGF axis.","authors":"Yan, Ke; Yang, Yiran; Han, Yi; Zhang, Yuhan; Zhou, Tong; Sun, Wenxin; Wang, Ruochen; Liu, Zhaolin; Zhang, Qinghe; Zhu, Linfangzi; Tan, Meidi; Huang, Caihong; Hu, Jiaoyue; Liu, Qiuping; Zhang, Zhaoqiang; Liu, Zuguo","year":2025,"journal":"The ocular surface, 38, 274-289","doi":"10.1016/j.jtos.2025.08.008","pmid":"40882778","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14314","title":"Role of EZH2 in regulating c-Myc stability through the E3 ubiquitin ligase HUWE1 in heart failure and its mechanisms.","authors":"Yan, Licheng; Xie, Deng; Huang, Tingfeng; Zheng, Haotian; Huang, Jie; Chen, Haiyu; Xie, Qi; Weng, Guoxing; Zheng, Fuzhen","year":2025,"journal":"Cellular signalling, 135, 111968","doi":"10.1016/j.cellsig.2025.111968","pmid":"40582435","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14315","title":"Enhanced Intracellular Delivery by Twisted CC-Loop Conformation in Cyclic Cell-Penetrating Peptides.","authors":"Yan, Qipeng; Jiang, Xingyue; Xie, Wei; Wu, Xia; Gong, Dalian; Li, Zenghui; Yuan, Dan; Shi, Junfeng","year":2025,"journal":"Biomacromolecules, 26(9), 5633-5644","doi":"10.1021/acs.biomac.5c00378","pmid":"40590454","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14316","title":"Recombinant production of isotope-labeled human α-defensin 5 via calmodulin fusion and insights into its expression enhancement.","authors":"Yan, Shaonan; Gu, Hao; Shibagaki, Mitsuki; Chrisnanto, Jeremia Oktavian; Hirai, Fumi; Kumeta, Hiroyuki; Kumaki, Yasuhiro; Yokoi, Yuki; Nakamura, Kiminori; Kikukawa, Takashi; Ayabe, Tokiyoshi; Arai, Tatsuya; Aizawa, Tomoyasu","year":2025,"journal":"Peptides, 191, 171425","doi":"10.1016/j.peptides.2025.171425","pmid":"40582509","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14317","title":"Relief of loperamide-induced constipation by peptidic and small molecule RXFP4 agonists in mice.","authors":"Yan, Shiyu; Chen, Yan; Wang, Jiang; Wang, Qiuying; Zhou, Qingtong; Liu, Hong; Wang, Ming-Wei; Yang, Dehua","year":2025,"journal":"Biochemical pharmacology, 237, 116924","doi":"10.1016/j.bcp.2025.116924","pmid":"40194608","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14318","title":"Apelin‑13 in the paraventricular nucleus (PVN) attenuates myocardial ischemia through V1a receptors in PVN/nucleus tractus solitarii (NTS) and GARγ2 in NTS.","authors":"Yan, Wen; Wang, Dan; Zhang, Xinmin; Xuan, Chengluan","year":2025,"journal":"International journal of molecular medicine, 56(6)","doi":"10.3892/ijmm.2025.5652","pmid":"41041849","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14319","title":"ALOX15 Aggravates Metabolic Dysfunction-Associated Steatotic Liver Disease in Mice with Type 2 Diabetes via Activating the PPARγ/CD36 Axis.","authors":"Yan, Wenhui; Cui, Xin; Guo, Tingli; Liu, Na; Wang, Zhuanzhuan; Sun, Yuzhuo; Shang, Yuanrui; Liu, Jieyun; Zhu, Yuanyuan; Zhang, Yangyang; Chen, Lina","year":2025,"journal":"Antioxidants & redox signaling, 43(1-3), 37-55","doi":"10.1089/ars.2024.0670","pmid":"39815992","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14320","title":"Dulaglutide markedly prevents peritoneal fibrosis in a rodent model of chronic kidney disease: Insights into the pathogenesis.","authors":"Yang, Chih-Chao; Yue, Ya; Wang, Yi-Ting; Chiang, John Y; Cheng, Ben-Chung; Hsu, Tsuen-Wei; Chen, Yi-Ling; Li, Yi-Chen; Yip, Hon-Kan","year":2025,"journal":"International journal of molecular medicine, 56(4)","doi":"10.3892/ijmm.2025.5592","pmid":"40709382","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14321","title":"Structure-activity relationship and molecular interaction mechanisms of the ACE-inhibitory tripeptide LL-X.","authors":"Yang, Cuicui; Cai, Mengmeng; Ma, Zhengkun; Liu, Pengru; Lan, Xiongdiao","year":2025,"journal":"Bioorganic chemistry, 164, 108905","doi":"10.1016/j.bioorg.2025.108905","pmid":"40884921","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14322","title":"Tirzepatide alleviates doxorubicin-induced cardiotoxicity via inhibiting HRD1-mediated Nrf2 ubiquitination.","authors":"Yang, Dan; Chen, Yang-Hao; Chen, Yan-Kun; Zeng, Ya-Lin; Ling, Zhi-Yu","year":2025,"journal":"Cardiovascular research, 121(12), 1865-1882","doi":"10.1093/cvr/cvaf033","pmid":"40036855","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tirzepatide (daily subcutaneous injection for 14 days) protected C57BL/6 mice from doxorubicin-induced myocardial injury, cardiac dysfunction, and mortality. Tirzepatide significantly reduced oxidative stress and cardiomyocyte apoptosis both in vivo and in H9c2 cells. RNA sequencing and molecular analysis revealed the mechanism: doxorubicin triggers ER stress that upregulates HRD1, an E3 ubiquitin ligase that ubiquitinates and degrades Nrf2. Tirzepatide prevents ER stress-induced HRD1 upregulation, thereby preserving Nrf2 protein expression, nuclear translocation, and transcriptional activity — ultimately protecting cardiomyocytes from oxidative damage and death. Ad-Hrd1 overexpression and siNrf2 knockdown confirmed the mechanism.","whyItMatters":"Chemotherapy-related heart damage is a major cause of illness and death in cancer survivors, and no approved drug prevents it. Tirzepatide is already FDA-approved and widely available, making clinical translation potentially rapid. The newly identified HRD1-Nrf2 mechanism provides a specific molecular target and explains why tirzepatide has cardioprotective effects beyond its metabolic actions. This could change how oncologists protect their patients' hearts during treatment.","specificNumbers":"","methodology":"Male C57BL/6 mice received daily subcutaneous tirzepatide or vehicle for 14 days, with doxorubicin (15 mg/kg single IP injection) to induce cardiotoxicity. Echocardiography, histological assessment, and molecular analyses measured cardiac outcomes. In vitro studies used H9c2 cardiomyocyte cells. RNA sequencing of heart tissue identified potential targets. Mechanistic confirmation used adenoviral HRD1 overexpression (Ad-Hrd1) and Nrf2 siRNA knockdown to prove the HRD1-Nrf2 pathway.","limitations":"Preclinical study in mice using a single high-dose doxorubicin model, which differs from the cumulative low-dose protocols used clinically. The 14-day treatment window is short relative to typical cancer treatment courses. Whether tirzepatide would interfere with doxorubicin's anti-tumor efficacy was not assessed — a critical concern for clinical translation. H9c2 cells are a rat cardiomyoblast line, not primary human cardiomyocytes. The GIP and GLP-1 receptor contributions were not individually dissected."},{"rthcId":"RPEP-14323","title":"Association of semaglutide use with outcomes in chronic plantar heel pain: a prospective observational cohort and a pilot interventional study.","authors":"Yang, Fan; Zhou, Lenian; Zhang, Jieyuan; Wang, Qiuke; Cai, Qianying; Wang, Jiazheng; Wu, Chenglin; Li, Xueqian; Zhang, Jinshan; Zheng, Yongqiang; Ma, Xin; Zhu, Hongyi; Shi, Zhongmin","year":2025,"journal":"International journal of surgery (London, England), 111(12), 9333-9341","doi":"10.1097/JS9.0000000000003156","pmid":"40788007","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14324","title":"A machine learning-driven transcriptomic study reveals the key role of Romo1 in reversing central sensitization through stellate ganglion block in migraine: An interventional study based on a recurrent migraine rat model.","authors":"Yang, Fei; Tian, Xiaomao; Xu, Yao; Yang, Shun; Tu, Shengfen; Jiang, Li","year":2025,"journal":"Headache","doi":"10.1111/head.14997","pmid":"40747904","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14325","title":"GLP-1 Agonists in Cardiovascular Diseases: Mechanisms, Clinical Evidence, and Emerging Therapies.","authors":"Yang, Han-Mo","year":2025,"journal":"Journal of clinical medicine, 14(19)","doi":"10.3390/jcm14196758","pmid":"41095837","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14326","title":"Hydrocarbon Stapling Enables Improvement of Antimicrobial Activity and Proteolytic Stability of Host-Defense Peptide Ocellatin-3N.","authors":"Yang, Hao; Yuan, Fei; Xie, Guangxu; Fu, Yinxue; Mi, Jia; Yu, Longjie; Liu, Weijia; Li, Yulei","year":2025,"journal":"Chembiochem : a European journal of chemical biology, 26(12), e202500204","doi":"10.1002/cbic.202500204","pmid":"40346704","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Hydrocarbon-stapled analogs of the antimicrobial peptide Oce-3N-0 showed remarkable improvements in both protease resistance and antimicrobial activity compared to the unmodified parent peptide.\n\nThe stapled analog Oce-3N-5 was identified as the most promising candidate, demonstrating broad-spectrum activity against both Gram-negative and Gram-positive pathogens while maintaining structural stability. The stapling approach successfully addressed the two main barriers to clinical development of this peptide class: unstable structure and susceptibility to proteolytic degradation.","whyItMatters":"The antibiotic resistance crisis demands new antimicrobial agents with novel mechanisms of action. Frog-derived antimicrobial peptides kill bacteria by disrupting their membranes — a mechanism that is much harder for bacteria to develop resistance against. Hydrocarbon stapling solves the stability problem that has prevented these peptides from becoming drugs, potentially unlocking an entire class of natural antibiotics for clinical use.","specificNumbers":"","methodology":"A series of hydrocarbon-stapled analogs of the antimicrobial peptide Oce-3N-0 were synthesized by incorporating non-natural amino acids at specific positions and cross-linking them with a hydrocarbon bridge. The analogs were evaluated for their chemical properties (structural stability), protease resistance, and antimicrobial activity against a panel of Gram-positive and Gram-negative bacteria using standard antimicrobial susceptibility testing.","limitations":"All testing was in vitro — no animal studies or toxicity assessments were reported. The specific MIC (minimum inhibitory concentration) values are not provided in the abstract, making it difficult to assess the magnitude of improvement. Hemolytic activity and mammalian cell cytotoxicity — critical safety parameters for antimicrobial peptides — are not mentioned. The manufacturing scalability and cost of stapled peptides may be challenging."},{"rthcId":"RPEP-14327","title":"Nociceptor α7nAChR activation blunts neuronal HMGB1 release and attenuates inflammation and nociceptive behavior.","authors":"Yang, Huan; Morgan, Timothy S; Petruzzelli, Serena; Hashimoto, Okito; Hepler, Tyler D; Tynan, Aisling; Chaudhry, Saher; Brines, Michael; Andersson, Ulf; Chavan, Sangeeta S; Tracey, Kevin J","year":2025,"journal":"Molecular medicine (Cambridge, Mass.), 31(1), 324","doi":"10.1186/s10020-025-01387-z","pmid":"41184776","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14328","title":"Design of Electrostatic Nanocomplex of Semaglutide with Protamine and Zinc for Subcutaneous Prolonged Delivery.","authors":"Yang, In Gyu; Kim, Jeong-Soo; Kang, Myung Joo","year":2025,"journal":"Nanomaterials (Basel, Switzerland), 15(18)","doi":"10.3390/nano15181399","pmid":"41003035","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14329","title":"Buckwheat protein-derived peptide ameliorates insulin resistance by directing O-linked N-acetylglucosamine transferase to regulate the SIRT1/PGC1α pathway.","authors":"Yang, Jiajun; Hou, Siyu; Zhao, Yuhui; Sun, Zhaoyang; Zhang, Lilin; Deng, Yan; Shang, Xiaoli; Yu, Hanjie; Li, Zheng; Li, Hongmei","year":2025,"journal":"International journal of biological macromolecules, 304(Pt 2), 140925","doi":"10.1016/j.ijbiomac.2025.140925","pmid":"39947565","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14330","title":"Recent Advances in Peptide Linkers of Antibody-Drug Conjugates.","authors":"Yang, Lu; Ma, Jiahui; Liu, Ben; Li, Yangbing; Ma, Yaping; Chen, Hao; Han, Zhijian","year":2025,"journal":"Journal of medicinal chemistry, 68(17), 18099-18113","doi":"10.1021/acs.jmedchem.5c01500","pmid":"40891142","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14331","title":"Programmable Food-Derived Peptide Coassembly Strategies for Boosting Targeted Colitis Therapy by Enhancing Oral Bioavailability and Restoring Gut Microenvironment Homeostasis.","authors":"Yang, Meng; Liu, Jingbo; Liu, Chunmei; Zhang, Hui; Li, Shanglin; Zhang, Ting; Yu, Zhipeng; Chi, Xiwen; Zhang, Zhihui; Du, Zhiyang","year":2025,"journal":"ACS nano, 19(1), 600-620","doi":"10.1021/acsnano.4c11108","pmid":"39745599","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14332","title":"Central neuropeptides as key modulators of astrocyte function in neurodegenerative and neuropsychiatric disorders.","authors":"Yang, Meng-Jie; Jia, Min; Cai, Meng; Feng, Xiao; Huang, Li-Ning; Yang, Jian-Jun","year":2025,"journal":"Psychopharmacology, 242(11), 2353-2371","doi":"10.1007/s00213-025-06840-9","pmid":"40536717","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies nine central neuropeptides that modulate astrocyte state transitions: neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), pituitary adenylate cyclase-activating polypeptide (PACAP), cholecystokinin (CCK), corticotropin-releasing hormone (CRH), angiotensin (Ang), oxytocin (OXT), orexin/hypocretin (OX/HCRT), and glucagon-like peptide-1 (GLP-1). These peptides influence astrocyte proliferation, morphology, and secretory functions, thereby affecting the pathogenesis of both neurodegenerative diseases (Alzheimer's, Parkinson's) and neuropsychiatric disorders (depression, anxiety). Both the neuropeptides and their receptors are positioned as promising therapeutic targets.","whyItMatters":"Most brain disease research focuses on neurons, but astrocytes play critical roles in brain health and disease that are only now being fully appreciated. Understanding how neuropeptides regulate astrocyte function opens a new therapeutic dimension — rather than targeting neurons directly, treatments could work by using peptides to shift astrocytes into protective modes. This is particularly relevant because several of these peptides (like GLP-1 and oxytocin) already have approved or experimental drug forms.","specificNumbers":"","methodology":"Narrative review of preclinical research literature examining the effects of nine selected central neuropeptides on astrocyte function and their roles in neurodegenerative and neuropsychiatric disease pathogenesis.","limitations":"As a narrative review, the study selection and synthesis methodology is not systematic. The evidence is almost entirely preclinical (cell culture and animal models), with limited human data. The complexity of astrocyte subtypes and regional brain differences may mean that peptide effects vary significantly by brain region and disease context. The review covers nine peptides broadly rather than providing deep mechanistic analysis of each."},{"rthcId":"RPEP-14333","title":"The role of GLP-1 receptor agonists in IBD-related surgery and IBD-related complications of inflammatory bowel disease among patients with metabolic comorbidities: a systematic review and meta-analysis.","authors":"Yang, Mengqi; Huo, Yujia; Liu, Zhining; Bai, Guannan; He, Dongjun; Zhang, Lin","year":2025,"journal":"Frontiers in medicine, 12, 1621958","doi":"10.3389/fmed.2025.1621958","pmid":"40917833","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14334","title":"Supramolecular peptide hydrogel epitope vaccine functionalized with CAR-T cells for the treatment of solid tumors.","authors":"Yang, Pengxiang; Yao, Xiaomin; Tian, Xue; Wang, Yuehan; Gong, Leilei; Yang, Yumin; Jie, Jing","year":2025,"journal":"Materials today. Bio, 31, 101517","doi":"10.1016/j.mtbio.2025.101517","pmid":"39925713","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The supramolecular peptide epitope vaccine encapsulated with CAR-T cells (SPEV-CAR-T) achieved multiple improvements over standard CAR-T therapy:\n\n- The peptide hydrogel scaffold promoted CAR-T cell proliferation, cytotoxic activity, and lymphocyte subpopulation transformation (from effector to memory phenotypes)\n- Complementary peptide epitopes from different extracellular domains of HER2 improved tumor antigen spreading and targeting efficiency\n- Sustained release from the hydrogel maintained both vaccine and CAR-T cell delivery over time\n- The system induced endogenous humoral and cellular immune responses alongside the exogenous CAR-T response\n- Critically, SPEV-CAR-T generated central memory T cells in systemic immune tissues — directly addressing the poor persistence problem of CAR-T therapy\n- Superior anti-tumor effects were demonstrated in an in vivo mouse model of solid tumors","whyItMatters":"CAR-T therapy has transformed treatment for blood cancers like leukemia and lymphoma, but solid tumors represent over 90% of all cancers and remain largely resistant to CAR-T. The two biggest challenges — limited CAR-T persistence and the immunosuppressive tumor microenvironment — are both addressed by this peptide hydrogel system. By combining a vaccine that activates the body's own immune system with engineered CAR-T cells in a single sustained-release platform, this approach creates a more comprehensive and durable anti-tumor immune response.","specificNumbers":"","methodology":"Researchers designed a self-assembling peptide that forms nanofiber scaffolds through non-covalent interactions of amphiphilic amino acids and ion stabilizers. Complementary peptide vaccine epitopes and CAR-T target sites were derived from different extracellular domains of HER2. The hydrogel was loaded with both the peptide epitope vaccine and CAR-T cells. In vitro experiments assessed CAR-T cell proliferation, cytotoxicity, and phenotype changes within the hydrogel. In vivo experiments in tumor-bearing mice evaluated anti-tumor efficacy, immune response induction (humoral and cellular), and central memory T cell generation in systemic immune tissues.","limitations":"All experiments were conducted in mouse tumor models, which may not accurately predict human immune responses or solid tumor behavior. The HER2-specific system would only apply to HER2-positive cancers. Manufacturing complexity of combining a peptide hydrogel vaccine with live CAR-T cells presents significant clinical translation challenges. Long-term safety of sustained peptide hydrogel release at tumor sites is unknown. The immune response in immunodeficient tumor-bearing mice may differ substantially from immunocompetent cancer patients. Specific tumor sizes, survival curves, and quantitative immune metrics were not detailed in the abstract."},{"rthcId":"RPEP-14335","title":"Effectiveness of Sodium-Glucose Transporter 2 Inhibitors and Semaglutide on Body Composition in Type 2 Diabetes Mellitus and Chronic Kidney Disease: A Real-World Cohort Study with Bioelectrical Impedance Analysis.","authors":"Yang, Qing; Qin, Chunmei; Lang, Yanlin; Yang, Wenjie; Yang, Fenghao; Yang, Jia; Liu, Ke; Yuan, Jiamin; Zou, Yutong; Liu, Fang","year":2025,"journal":"Diabetes, metabolic syndrome and obesity : targets and therapy, 18, 2885-2897","doi":"10.2147/DMSO.S531413","pmid":"40837607","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14336","title":"Cardiovascular Safety of Anti-CGRP Monoclonal Antibodies in Older Adults or Adults With Disability With Migraine.","authors":"Yang, Seonkyeong; Orlova, Yulia; Park, Haesuk; Smith, Steven M; Guo, Yi; Chapin, Benjamin A; Wilson, Debbie L; Lo-Ciganic, Wei-Hsuan","year":2025,"journal":"JAMA neurology, 82(2), 132-141","doi":"10.1001/jamaneurol.2024.4537","pmid":"39761027","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14337","title":"Pharmacological interventions for addressing pediatric and adolescent obesity: A systematic review and network meta-analysis.","authors":"Yang, Shuo; Xin, Shuangqing; Ju, Ronghui; Zang, Peizhuo","year":2025,"journal":"PloS one, 20(2), e0314787","doi":"10.1371/journal.pone.0314787","pmid":"40014613","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14338","title":"Optic disc edema during semaglutide therapy: case report and literature review.","authors":"Yang, Tingting; Chen, Aiming; Zeng, Feng; Liu, Jiayan; Kamilijiang, Yilali; Yuan, Bowei; Lu, Yamei; Jin, Guangming","year":2025,"journal":"American journal of ophthalmology case reports, 40, 102476","doi":"10.1016/j.ajoc.2025.102476","pmid":"41311659","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14339","title":"Novel ACE-Inhibitory Peptides from Royal Jelly Proteins: Comprehensive Screening, Mechanistic Insights, and Endothelial Protection.","authors":"Yang, Wanyu; Zou, Xinyu; Zhang, Tianrong; Liu, Qingqing; Liu, Ziyan; Li, Fan; Luo, Yuhong; Wang, Yiwen; Qiu, Zhijun; Zhang, Bin","year":2025,"journal":"Foods (Basel, Switzerland), 15(1)","doi":"10.3390/foods15010084","pmid":"41517150","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"From three major royal jelly proteins (MRJP1-3), 1,411 unique peptides were generated through simulated digestion. After virtual screening for bioactivity, safety, and drug-like properties, 27 candidates were selected. Two peptides — PYPDWSFAK and RPYPDWSF — showed potent ACE inhibition with IC50 values of 110 μmol/L and 204 μmol/L, respectively.\n\nPYPDWSFAK acted as a mixed-type ACE inhibitor, forming multiple hydrogen bonds with key residues in the ACE active site and directly coordinating with the catalytic zinc ion. In cell studies, PYPDWSFAK was non-toxic, blocked angiotensin II-induced endothelial cell migration, restored the balance of nitric oxide (NO) and endothelin-1 (ET-1), and boosted antioxidant enzyme activities (SOD and GSH-Px).","whyItMatters":"High blood pressure is one of the most common chronic health conditions worldwide, and many people seek natural alternatives to pharmaceutical ACE inhibitors like captopril. Identifying potent ACE-inhibitory peptides from a natural source like royal jelly opens the door to developing functional foods or supplements that could help manage blood pressure with fewer side effects.","specificNumbers":"","methodology":"The researchers used computer simulations to digest three major royal jelly proteins with 16 different enzyme combinations, generating 1,411 unique peptide fragments. These were screened virtually for predicted bioactivity, toxicity, solubility, and drug-like properties. The top 27 candidates were tested in molecular docking simulations against ACE, and the best performers were validated in lab-based ACE inhibition assays and cell culture experiments using endothelial cells.","limitations":"This study was conducted entirely in computer simulations and cell cultures — there were no animal or human trials to confirm whether these peptides lower blood pressure in a living organism. The peptides' stability during actual digestion, their absorption in the gut, and their bioavailability in the bloodstream remain unknown. The IC50 values, while promising, are higher than captopril, meaning larger doses might be needed for a therapeutic effect."},{"rthcId":"RPEP-14340","title":"Research Progress on the Association Between GLP-1 Receptor Agonists and Cardiomyopathy.","authors":"Yang, Xiao; Li, Xinghui","year":2025,"journal":"Reviews in cardiovascular medicine, 26(8), 37180","doi":"10.31083/RCM37180","pmid":"40927090","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14341","title":"Nociceptor-derived CGRP enhances dermal type I conventional dendritic cell function to drive autoreactive CD8+ T cell responses in vitiligo.","authors":"Yang, Xiuli; Ding, Wenxiang; Lou, Fangzhou; Xu, Hao; Sheng, Anqi; Sun, Yang; Cai, Xiaojie; Zhou, Miaoni; Lin, Fuquan; Jin, Rong; Zheng, Xichen; Wang, Zhikai; Deng, Siyu; Xu, Zhenyao; Zhang, Taiyu; Cheng, Jinke; Zheng, Xingdong; Xu, Aie; Wang, Honglin","year":2025,"journal":"Immunity, 58(8), 2086-2103.e9","doi":"10.1016/j.immuni.2025.05.018","pmid":"40527324","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14342","title":"Genetic evidence for repurposing GLP-1 receptor agonists in chronic kidney disease and IgA nephropathy: Metabolic and anti-inflammatory pathways beyond glycaemic control.","authors":"Yang, Xueying; Tang, Wenhao; Chan, Han; Wang, Mo; Yang, Haiping; Li, Qiu","year":2025,"journal":"Diabetes, obesity & metabolism, 27(12), 7395-7407","doi":"10.1111/dom.70144","pmid":"40994081","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Genetically predicted GLP-1R activation significantly reduced risks of CKD (OR 0.83, p=9.22E-9), IgA nephropathy (OR 0.70, p=2.11E-3), and preserved kidney function (eGFR β=0.01, p=9.11E-3). Effects on other CKD subtypes (membranous nephropathy, nephrotic syndrome, chronic glomerulonephritis) were null.\n\nMediation analysis revealed FGF23 suppression as the dominant pathway, mediating 26.57% of the eGFR effect and 13.50% of CKD protection. Metabolic mediators contributed modestly: BMI (2.08% for CKD, 5.51% for eGFR), HDL (0.79% for CKD), and HbA1c (8.25% for eGFR). For IgA nephropathy specifically, only BMI showed a mediation effect.","whyItMatters":"Chronic kidney disease affects over 800 million people globally and IgA nephropathy is the most common primary glomerular disease worldwide with limited treatment options. Genetic evidence for GLP-1 drugs' kidney benefits — especially through a novel FGF23 pathway rather than just glucose control — could accelerate clinical trials for these kidney diseases and expand the therapeutic scope of an already widely used drug class.","specificNumbers":"","methodology":"Two-sample Mendelian randomization using large-scale GWAS data to estimate causal effects of GLP-1R activation on kidney outcomes. Positive control analyses validated instruments using HbA1c, blood glucose, T2DM, and diabetic nephropathy. Mediation MR assessed pathways through BMI, lipids, glycemic markers, and inflammatory proteins. Data from MRC IEU OpenGWAS, FinnGen, GWAS Catalogue, and cohort studies.","limitations":"Mendelian randomization assumes genetic variants only affect outcomes through the proposed pathway, which may not always hold. Data were primarily from European ancestry populations, limiting generalizability. This is genetic evidence for causality, not clinical trial evidence. The null results for some CKD subtypes suggest the kidney protection is not universal across all kidney diseases. FGF23 mediation, while significant, leaves most of the protective mechanism unexplained."},{"rthcId":"RPEP-14343","title":"Research on the effects of GLP-1 receptor agonists in treating cognitive dysfunction and gait disorders in elderly patients with diabetes.","authors":"Yang, Yang; Chen, Lifeng; Zhang, Yanjun; Fu, Wenqian; Liu, Dandan; Jiang, Tianyu","year":2025,"journal":"Frontiers in pharmacology, 16, 1607443","doi":"10.3389/fphar.2025.1607443","pmid":"40630129","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14344","title":"Design of potent and proteolytically stable double biaryl-stapled GLP-1R/GIPR peptide dual agonists.","authors":"Yang, Yifang; Lin, Qing","year":2025,"journal":"Bioorganic & medicinal chemistry, 125, 118215","doi":"10.1016/j.bmc.2025.118215","pmid":"40311601","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The double-stapled and α-methylated peptide DA23-Bpy10,17Bpy21,28 demonstrated more potent and balanced dual agonist activity at both GLP-1R and GIPR compared to tirzepatide. It achieved a half-life of 30 minutes in simulated intestinal fluid, representing a significant improvement in proteolytic stability over earlier single-stapled versions.\n\nIn oral glucose tolerance tests in rodents, the peptide showed glucose-lowering activity equal to semaglutide, suggesting it could be a viable candidate for oral delivery of dual-agonist therapy.","whyItMatters":"Injectable GLP-1-based drugs have transformed diabetes and obesity treatment, but many patients would prefer an oral option. Current dual agonists like tirzepatide break down too quickly in the gut for oral delivery. This study demonstrates a chemical strategy that could make oral dual-agonist peptide drugs a reality, potentially improving patient adherence and expanding access to these powerful therapies.","specificNumbers":"","methodology":"The researchers used a medicinal chemistry approach, designing and synthesizing peptide analogs with two biaryl staples and α-methylation modifications to increase resistance to enzymatic breakdown. They tested the peptides for receptor activation at GLP-1R and GIPR in cell-based assays, measured proteolytic stability in simulated intestinal fluid, and evaluated blood sugar-lowering effects using oral glucose tolerance tests in rodents.","limitations":"The study was conducted in rodent models, and results may not directly translate to humans. The 30-minute half-life in simulated intestinal fluid, while improved, may still need further optimization for practical oral dosing. No pharmacokinetic or long-term safety data were reported. The peptides have not yet been tested in human clinical trials."},{"rthcId":"RPEP-14345","title":"Transcriptomics and proteomics characterizing the antioxidant mechanisms of semaglutide in diabetic mice with cognitive impairment.","authors":"Yang, Ying; Song, Lulu; Yu, Liping; Zhang, Jinping; Zhang, Bo","year":2025,"journal":"International journal of molecular medicine, 55(4)","doi":"10.3892/ijmm.2025.5497","pmid":"39886945","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14346","title":"The P2Y13 receptor-mediated microglial morphological transformation through the p38MAPK signaling pathway contributes to central sensitization in a murine model of chronic migraine.","authors":"Yang, Yingjie; Sun, Suya; Qin, Pengtao; Sun, Yalun; Li, Huijuan; Wang, Diandian; He, Xin; Ge, Zhaoming; Fan, Zhenzhen; Zhang, Jiewen; Sun, Songtang","year":2025,"journal":"The journal of headache and pain, 27(1), 8","doi":"10.1186/s10194-025-02251-5","pmid":"41398220","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14347","title":"Tirzepatide alleviates oxidative stress and inflammation in diabetic nephropathy via IL-17 signaling pathway.","authors":"Yang, Yong; Wang, Yiyong; Zhou, Yong; Deng, Jing; Wu, Lihao","year":2025,"journal":"Molecular and cellular biochemistry, 480(2), 1241-1254","doi":"10.1007/s11010-024-05066-1","pmid":"38965127","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tirzepatide (at doses of 3 and 10 nmol/kg) administered for 8 weeks to diabetic mice reduced serum creatinine, blood urea nitrogen, and advanced glycosylation end products while promoting insulin secretion. It attenuated tubular and glomerular injury, reduced kidney cell death, increased antioxidant enzymes (SOD and CAT), decreased the oxidative stress marker MDA, and lowered pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) in both serum and kidney tissue.\n\nThe mechanism was traced to inhibition of the IL-17 pathway: when researchers administered an IL-17 pathway agonist (IL-17A), it reversed tirzepatide's suppressive effects on oxidative stress and inflammation, confirming this pathway as the key mediator.","whyItMatters":"Diabetic kidney disease is a leading cause of kidney failure worldwide, and current treatments have limited ability to halt its progression. This study reveals that tirzepatide — already approved for diabetes and obesity — may offer kidney-protective benefits beyond blood sugar control, working through anti-inflammatory and antioxidant mechanisms that could expand its therapeutic applications.","specificNumbers":"","methodology":"Diabetic nephropathy was induced in mice via intraperitoneal injection of streptozotocin (60 mg/kg). Mice then received tirzepatide at two doses (3 and 10 nmol/kg) via intraperitoneal injection for 8 weeks. Researchers measured kidney biochemical indicators, histopathology, apoptosis levels, oxidative stress markers, inflammatory cytokines, and IL-17 pathway components. An IL-17 pathway agonist was used to validate the mechanism.","limitations":"This was a mouse study using chemically induced diabetes (streptozotocin), which may not fully replicate human type 2 diabetic nephropathy. Tirzepatide was administered intraperitoneally rather than subcutaneously as in human use. The study did not assess long-term outcomes or whether kidney protection persisted after treatment cessation. Specific quantitative improvements (percentage changes) were not reported in the abstract."},{"rthcId":"RPEP-14348","title":"Exploring glucagon-like peptide-1 receptor agonists as potential disease-modifying agents in autoimmune diseases.","authors":"Yang, Yuanyuan; Liu, Wencong; Zhang, Zechang; Zhang, Yujia; Wang, Xuebin; Wang, Jing; Cai, Huaifang; Liu, Yichan; Meng, Ran; Fu, Yuqi; Luo, Hongmin; Yang, Lei; Liu, Wenxuan","year":2025,"journal":"Journal of autoimmunity, 153, 103414","doi":"10.1016/j.jaut.2025.103414","pmid":"40174283","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Using 22 significant cis-eQTL single-nucleotide polymorphisms as genetic instruments, the study found that increased GLP-1R gene expression had a significant protective effect on type 1 diabetes, hypothyroidism, primary biliary cholangitis (PBC), and rheumatoid arthritis (RA). Conversely, it was associated with increased risk of Graves' disease (GD), ulcerative colitis (UC), and psoriasis.\n\nPositive control analysis confirmed the methodology's validity: GLP-1R agonists were significantly associated with reduced obesity risk (OR = 0.826, p = 0.021) and reduced type 2 diabetes risk (OR = 0.886, p < 0.001), consistent with their known clinical effects. Results were validated across two independent databases (IEU OpenGwas and FinnGen) via meta-analysis.","whyItMatters":"With millions of people now taking GLP-1 receptor agonists for diabetes and obesity, understanding their effects on autoimmune diseases is crucial. This study provides the first systematic genetic evidence that these peptide drugs may have both beneficial and harmful effects on different autoimmune conditions, which could guide prescribing decisions for patients with or at risk of these diseases.","specificNumbers":"","methodology":"The researchers used Mendelian randomization (MR), a method that uses genetic variants as natural experiments to infer causal relationships. They identified 22 genetic variants (cis-eQTLs) that influence GLP-1 receptor expression and used these as proxies for GLP-1R agonist exposure. They tested associations with 18 autoimmune diseases using data from two large genetic databases (IEU OpenGwas and FinnGen), then combined results via meta-analysis.","limitations":"Mendelian randomization estimates causal effects from genetic proxies, not actual drug exposure, so results may not perfectly reflect clinical drug effects. The study could not account for dosing, duration, or specific GLP-1R agonist used. The genetic data is primarily from European populations, limiting generalizability. Some autoimmune diseases had relatively small case numbers in the databases, which could affect statistical power."},{"rthcId":"RPEP-14349","title":"Sex Differences in the Efficacy of Glucagon-Like Peptide-1 Receptor Agonists for Weight Reduction: A Systematic Review and Meta-Analysis.","authors":"Yang, Yucheng; He, Liyun; Han, Shumeng; Yang, Na; Liu, Yiwen; Wang, Xuechen; Li, Ziyi; Ping, Fan; Xu, Lingling; Li, Wei; Zhang, Huabing; Li, Yuxiu","year":2025,"journal":"Journal of diabetes, 17(3), e70063","doi":"10.1111/1753-0407.70063","pmid":"40040445","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14350","title":"Emerging self-assembled peptide hydrogels for enhanced wound healing.","authors":"Yang, Zixin; Wang, Yinglu; Zhu, Hu","year":2025,"journal":"Nanomedicine (London, England), 20(17), 2217-2236","doi":"10.1080/17435889.2025.2544535","pmid":"40799046","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14351","title":"Phenotypic Analysis of Persistent Atrial Fibrillation Focusing on Postablation Prognosis Using Brain Natriuretic Peptide-Related Factors.","authors":"Yano, Masamichi; Egami, Yasuyuki; Kobayashi, Noriyuki; Sugino, Ayako; Abe, Masaru; Ohsuga, Mizuki; Nohara, Hiroaki; Kawanami, Shodai; Ukita, Kohei; Kawamura, Akito; Yasumoto, Koji; Okamoto, Naotaka; Matsunaga-Lee, Yasuharu; Nishino, Masami","year":2025,"journal":"The American journal of cardiology, 256, 8-15","doi":"10.1016/j.amjcard.2025.06.037","pmid":"40669549","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14352","title":"Insulin resistance: The role in comorbid type 2 diabetes mellitus and depression.","authors":"Yao, Jia; Zhu, Chang-Qing; Sun, Yan; Huang, Yi-Wen; Li, Qing-Hua; Liao, Hui-Min; Deng, Xue-Jian; Li, Wan-Mei","year":2025,"journal":"Neuroscience and biobehavioral reviews, 175, 106218","doi":"10.1016/j.neubiorev.2025.106218","pmid":"40403856","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14353","title":"Functionalized Periosteum-Derived Microsphere-Hydrogel with Sequential Release of E7 Short Peptide/miR217 for Large Bone Defect Repairing.","authors":"Yao, Jun; Zu, Dan; Dong, Qi; Xia, Jiajie; Wang, Xiaonan; Guo, Jingjing; Ma, Gaoxiang; Wu, Bing; Fang, Bin","year":2025,"journal":"Biomaterials research, 29, 0127","doi":"10.34133/bmr.0127","pmid":"39780960","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14354","title":"Short peptide hydrogel with angular structure for hydrophobic antitumor drug delivery and controlled release.","authors":"Yao, Qingqing; Gao, Jie; Liu, Linsheng; Shi, Jinfang; Zafar, Hajra; Khan, Muhammad Ijaz; Zhu, Jianguo; Raza, Faisal; Zhu, Ying","year":2025,"journal":"Colloids and surfaces. B, Biointerfaces, 254, 114793","doi":"10.1016/j.colsurfb.2025.114793","pmid":"40381291","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The short peptide KK (sequence: KIKIDPPIKIK) has an angular structure created by its proline-proline core that enables it to form a network hydrogel under neutral pH, trapping hydrophobic paclitaxel. Under the slightly acidic conditions found in tumors, the gel structure changes and releases the drug in a sustained manner.\n\nIn vitro and in vivo experiments demonstrated that the drug-loaded hydrogel improved anti-tumor efficacy while showing good biocompatibility and biological safety. The peptide's functional properties are achieved with only 10 amino acids, making it cheaper and easier to synthesize than longer peptide-based delivery systems.","whyItMatters":"Many powerful chemotherapy drugs like paclitaxel are limited by poor solubility and harsh side effects when given systemically. Peptide hydrogels that respond to tumor acidity could deliver drugs locally with sustained release, reducing side effects while maintaining or improving efficacy. The fact that this works with just 10 amino acids makes it potentially practical and affordable to manufacture.","specificNumbers":"","methodology":"The peptide was synthesized using solid-phase peptide synthesis. Its structure was examined under neutral and acidic conditions using transmission electron microscopy and circular dichroism. Drug release was measured in vitro. Injectability was confirmed through rheological testing. Anti-tumor efficacy was tested in cell culture (in vitro cytotoxicity) and in tumor-bearing mice (in vivo). Biocompatibility was assessed both in cells and in animals.","limitations":"The study was conducted in cell lines and mice, not humans. The abstract does not report specific tumor reduction percentages or survival data. Long-term stability of the hydrogel in vivo and its performance with drugs other than paclitaxel were not addressed."},{"rthcId":"RPEP-14355","title":"How does oxytocin modulate human behavior?","authors":"Yao, Shuxia; Kendrick, Keith M","year":2025,"journal":"Molecular psychiatry, 30(4), 1639-1651","doi":"10.1038/s41380-025-02898-1","pmid":"39827220","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review proposes a hierarchical model of oxytocin's behavioral effects: it first enhances attention to salient social stimuli, then modulates cognitive, emotional, and reward processing in a person- and context-dependent manner. These effects promote interpersonal social understanding, attraction, and bonds on one hand, and social group cohesion through conformity, altruistic punishment, and moral emotions on the other. Importantly, oxytocin acts indirectly through neuromodulatory interactions with classical neurotransmitters and other peptides. Peripheral effects, particularly via the vagus nerve, may be more significant than originally understood.","whyItMatters":"Oxytocin has been one of the most studied neuropeptides for potential psychiatric applications, but clinical translation has been disappointing. This review addresses why by providing a more nuanced understanding of how oxytocin actually works — not as a simple social bonding switch, but as a complex neuromodulator whose effects depend on individual differences and context. This reframing is essential for designing better clinical trials and identifying which patients might truly benefit from oxytocin-based therapies.","specificNumbers":"","methodology":"Narrative review of both animal model and human studies on oxytocin, covering natural release triggers, functional effects, mechanisms of exogenous administration, and clinical trial progress in autism spectrum disorder and schizophrenia.","limitations":"As a narrative review, this does not include systematic methodology. The proposed hierarchical model, while integrative, is conceptual and not yet fully validated experimentally. Much human oxytocin research relies on intranasal administration, and the actual brain penetration and mechanism of action of exogenous oxytocin remains debated. The review acknowledges that clinical trials for autism and schizophrenia have shown mixed results."},{"rthcId":"RPEP-14356","title":"The efficacy and safety of thymosin alpha-1 combined with lenvatinib plus sintilimab in unresectable hepatocellular carcinoma: a retrospective study.","authors":"Yao, Siyang; Huang, Qiangsong; Zou, Yan; Liu, Tianqi; Yang, Yongyu; Huang, Tao; Zhao, Yuanquan; Dong, Xiaofeng","year":2025,"journal":"Scientific reports, 15(1), 13960","doi":"10.1038/s41598-025-97160-7","pmid":"40263352","tags":["thymosin-alpha-1"],"studyType":"observational-study","evidenceStrength":"moderate","keyFinding":"Adding thymosin alpha-1 (a peptide that boosts immune function) to a combination of lenvatinib (a targeted therapy) and sintilimab (a checkpoint inhibitor) significantly improved outcomes in unresectable liver cancer. Patients receiving the triple combination lived a median of 16 months compared to 11 months without thymosin alpha-1 — a 5-month survival advantage (p=0.018).\n\nProgression-free survival nearly doubled: 7 months vs. 4 months (p=0.006). The tumor response rate was also higher at 55.8% vs. 34.7% (p=0.042). Crucially, adding thymosin alpha-1 did not increase side effects — adverse event rates were similar between groups.","whyItMatters":"Unresectable liver cancer has limited treatment options and poor prognosis. This study suggests thymosin alpha-1 may enhance the effectiveness of modern cancer immunotherapy by strengthening the immune system's ability to attack tumors — without adding toxicity. If confirmed in larger trials, this peptide could become a standard addition to liver cancer treatment regimens.","specificNumbers":"n=92 (43 experimental, 49 control) · median OS 16 vs 11 months (p=0.018) · median PFS 7 vs 4 months (p=0.006) · ORR 55.8% vs 34.7% (p=0.042) · DCR 76.7% vs 59.2% (p=0.073) · no difference in adverse events","methodology":"Retrospective study of 92 patients with unresectable hepatocellular carcinoma treated at a single Chinese hospital from January 2020 to June 2022. Patients were divided into two groups based on treatment: thymosin alpha-1 plus lenvatinib and sintilimab (n=43) versus lenvatinib and sintilimab alone (n=49). Tumor responses were evaluated using mRECIST criteria. Adverse events were graded using CTCAE version 5.0.","limitations":"This is a retrospective, single-center study without randomization. Treatment group assignment was based on physician choice, introducing potential selection bias. The sample size of 92 patients limits statistical power. Being conducted at one Chinese hospital, results may not generalize to other populations. A prospective randomized trial would provide stronger evidence."},{"rthcId":"RPEP-14357","title":"Liver as a key organ for systemic antimicrobial defense.","authors":"Yao, Tiantian; Maccioni, Luca; Guan, Yukun; Rodrigues, Robim M; Gao, Bin","year":2025,"journal":"Hepatology communications, 9(12)","doi":"10.1097/HC9.0000000000000814","pmid":"41325136","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14358","title":"Semaglutide reduces cardiovascular events in type 2 diabetes: a systematic review and meta-analysis highlighting enhanced benefits in chronic kidney disease.","authors":"Yao, Yanni; Liu, Nairong; Chen, Siyan; Sun, Meng; Guo, Yanjie","year":2025,"journal":"European journal of medical research, 30(1), 1059","doi":"10.1186/s40001-025-03241-8","pmid":"41188987","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 17 studies with 40,632 patients, oral semaglutide significantly reduced cardiovascular death by 23% (HR 0.77), major adverse cardiovascular events (MACE) by 18% (HR 0.82), nonfatal heart attacks by 18% (HR 0.82), and nonfatal stroke by 32% (HR 0.68) compared to placebo.\n\nThe cardiovascular benefits were most pronounced in patients who also had chronic kidney disease (CKD), with risk reductions of 24–37% compared to 13–35% in those with type 2 diabetes alone or with existing cardiovascular disease. Semaglutide also lowered systolic blood pressure by 8 mmHg and LDL cholesterol by about 13 mg/dL, though it did not significantly affect kidney function markers like eGFR or UACR.","whyItMatters":"Heart disease is the leading cause of death in people with type 2 diabetes, and the risk is even higher for those who also have kidney disease. This meta-analysis provides the strongest evidence to date that semaglutide not only helps with blood sugar control but also substantially reduces the risk of heart attacks, strokes, and cardiovascular death — particularly in the highest-risk patients with co-existing kidney disease. This positions semaglutide as a multi-benefit treatment rather than just a diabetes drug.","specificNumbers":"","methodology":"The researchers conducted a systematic review and meta-analysis, searching four major medical databases (PubMed, Embase, Cochrane, and Web of Science) for studies published through September 2025. They included both randomized controlled trials and observational studies that compared oral semaglutide to placebo in people with type 2 diabetes. Data from 17 studies were combined using hazard ratios and mean differences with 95% confidence intervals.","limitations":"The analysis combined both randomized controlled trials and observational studies, which may introduce bias. The study focused on oral semaglutide versus placebo, so results may not directly apply to injectable forms. Despite the large total sample size, the CKD subgroup analyses had fewer patients and should be interpreted with some caution. The analysis also could not determine the specific biological mechanisms behind the enhanced benefits seen in kidney disease patients."},{"rthcId":"RPEP-14359","title":"Glucagon-like peptide-1 receptor agonists, inflammation, and kidney diseases: evidence from Mendelian randomization.","authors":"Yao, Yu-Xuan; Tang, Chen; Si, Feng-Lei; Lv, Ji-Cheng; Shi, Su-Fang; Zhou, Xu-Jie; Liu, Li-Jun; Zhang, Hong","year":2025,"journal":"Renal failure, 47(1), 2478488","doi":"10.1080/0886022X.2025.2478488","pmid":"40230199","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Genetically proxied GLP-1 receptor agonist exposure was significantly associated with decreased risk of two kidney diseases:\n\n- Diabetic nephropathy: OR = 0.72 (95% CI: 0.54-0.97, p = 0.031) — a 28% risk reduction\n- IgA nephropathy: OR = 0.58 (95% CI: 0.36-0.94, p = 0.027) — a 42% risk reduction\n\nTwo-stage network Mendelian randomization revealed that 34.27% (95% CI: 1.47-67.03%, p = 0.041) of the GLP-1 receptor agonist effect on IgA nephropathy was mediated through SLAMF1 (signaling lymphocytic activation molecule family member 1), an inflammatory protein. No significant associations were found with membranous nephropathy, nephrotic syndrome, chronic kidney disease, acute or chronic glomerulonephritis, or kidney stones.","whyItMatters":"This study provides genetic evidence that GLP-1 receptor agonists — already widely used for diabetes and obesity — may have protective effects on kidney diseases beyond their metabolic benefits. The finding for IgA nephropathy is particularly significant because this is a common autoimmune kidney disease with limited treatment options. Identifying SLAMF1 as a mediator suggests a specific anti-inflammatory mechanism that could guide future research and potentially expand the therapeutic use of GLP-1 drugs.","specificNumbers":"","methodology":"The researchers used two-sample Mendelian randomization (MR), a genetic epidemiology method that uses naturally occurring genetic variants (cis-eQTLs for GLP1R) as proxies for drug exposure to estimate causal effects while minimizing confounding. They tested associations between genetically proxied GLP-1 receptor activation and eight kidney diseases across discovery and validation cohorts. Type 2 diabetes and BMI served as positive controls. Two-stage network MR was used to identify inflammatory protein mediators of the observed effects.","limitations":"Mendelian randomization uses genetic proxies rather than actual drug exposure, so results may not perfectly translate to clinical practice. The effect sizes and confidence intervals are wide, particularly for the mediation analysis. The study primarily used European-ancestry genetic data, limiting generalizability. MR assumes the genetic variants only affect kidney disease through GLP-1 receptor activation (no horizontal pleiotropy), which may not hold for all variants. Clinical trials would be needed to confirm these genetically predicted effects."},{"rthcId":"RPEP-14360","title":"Adherence and Effectiveness of Liraglutide in Adolescents with Obesity.","authors":"Yaron, Shlomit; Arbel, Ronen; Razi, Talish; Nemet, Dan","year":2025,"journal":"Childhood obesity (Print)","doi":"10.1177/21532176251385715","pmid":"41047941","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14361","title":"Immunomodulatory Effects of Ticagrelor in Myocardial Infarction: Shifting the Cytokine Balance Toward an Anti-Inflammatory Profile.","authors":"Yaseen Sulaiman, Delan; Ahmad Merza Mohammad, Talar","year":2025,"journal":"Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research, 45(11), 365-374","doi":"10.1177/10799907251394220","pmid":"41192834","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14362","title":"Melanotan II nasal spray: a possible risk factor for oral mucosal malignant melanoma?","authors":"Yassin Alsabbagh, A; Bhujel, N; Singh, R P","year":2025,"journal":"International journal of oral and maxillofacial surgery, 54(9), 806-808","doi":"10.1016/j.ijom.2025.03.014","pmid":"40210573","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14363","title":"Injectable drugs for weight management.","authors":"Yates, Natasha; South, Terri-Lynne","year":2025,"journal":"Australian prescriber, 48(6), 197-202","doi":"10.18773/austprescr.2025.052","pmid":"41416056","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14364","title":"In vitro Antimicrobial Activities of Temporin A and Apidaecin B Peptides Against Clinical Strains Isolated from Blood Culture.","authors":"Yayla, İrem; Aydoğan, Okan; Kılıç, Ayşenur; Sirekbasan, Leyla; Tosun, Ayşe İstanbullu; Kocazeybek, Bekir; Dinç, Harika Öykü","year":2025,"journal":"Journal of clinical practice and research, 47(2), 223-226","doi":"10.14744/cpr.2025.96095","pmid":"41623671","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14365","title":"Sensory and Sympathetic Nerve Localization in Mouse Temporomandibular Joint and Knee Joint Neuro-Musculoskeletal Tissues.","authors":"Ye, Qianlin; Mohammadi, Aida; Zhang, Xinli; Kaczor-Urbanowicz, Karolina Elżbieta; Kapila, Sunil","year":2025,"journal":"Orthodontics & craniofacial research, 28 Suppl 1(Suppl 1), S110-S117","doi":"10.1111/ocr.70031","pmid":"40948222","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14366","title":"Delivery Routes of Topical Eyedrops Reaching the Posterior Segment of the Eye-Recent Advances.","authors":"Ye, Yuhong; Zhang, Ye; Zhao, Pan; Shen, Yaobang; Hu, Ping; Wang, Lei; Long, Da","year":2025,"journal":"Chemistry (Weinheim an der Bergstrasse, Germany), 31(72), e02324","doi":"10.1002/chem.202502324","pmid":"41277033","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies three main routes by which topical eyedrops can reach the posterior segment of the eye: the corneal route, the conjunctival-vasculature route, and the conjunctival-scleral route. Different peptide-based technologies favor different pathways:\n\n- Cell-penetrating homing peptides and lipid nanoparticle-encapsulated eyedrops primarily use the corneal route\n- Cell-penetrating peptides and PepT-1-targeting ligands mainly use the conjunctival route\n- Supramolecular peptide-based eyedrops, chitosan nanoparticles, and polymeric micelles can access the posterior segment through both routes\n\nNo topical eyedrop formulation has yet been clinically approved for treating ocular fundus (back-of-eye) diseases.","whyItMatters":"Millions of people with conditions like age-related macular degeneration and diabetic retinopathy currently rely on regular eye injections (intravitreal injections) that are painful, invasive, and require clinical visits. If peptide-based eyedrops can effectively deliver drugs to the back of the eye, it would be a transformative improvement in quality of life for these patients. This review maps the landscape of current approaches and their mechanisms.","specificNumbers":"","methodology":"This is a narrative review article that systematically summarizes recent advances in topical eyedrop therapies for posterior segment eye diseases. The authors categorized delivery technologies by their routes of access (corneal vs. conjunctival) and examined the mechanisms by which each formulation type crosses ocular barriers.","limitations":"As a review article, this paper synthesizes existing research rather than presenting new experimental data. No eyedrop formulation for posterior segment diseases has reached clinical approval yet, so all approaches discussed remain experimental. The translation from preclinical models to human use is a major hurdle that many of these technologies have not yet cleared. Long-term safety data for most peptide-based formulations are limited."},{"rthcId":"RPEP-14367","title":"Nociceptive Nerve-Derived CGRP Exacerbates Uterine Fibrogenesis in Adenomyosis by Promoting CD140b+ CD146+ Fibroblast Differentiation.","authors":"Ye, Zi; Zhao, Anning; Li, Xia; Hao, Yanqing; Huang, Dong; Chen, Jianmin; Li, Tiantian; Dai, Yangyang; Sun, Wenchao; Ma, Lie; Zhang, Songying; Xin, Liaobing","year":2025,"journal":"Advanced science (Weinheim, Baden-Wurttemberg, Germany), 12(45), e07128","doi":"10.1002/advs.202507128","pmid":"40985151","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CGRP-positive nociceptive nerves were overexpressed within fibrotic lesions in both human adenomyosis patients and mouse models. The peptide CGRP activated the ERK signaling pathway in RAMP1-high CD140b+CD146+ fibroblasts, driving them toward an extracellular matrix deposition phenotype that worsens fibrosis.\n\nAblating nociceptive nerves reduced uterine fibrosis in mice with induced adenomyosis. Treatment with rimegepant, an FDA-approved CGRP/RAMP1 antagonist, alleviated fibrosis progression and promoted fertility restoration in the mouse model.","whyItMatters":"This study reveals a previously unknown connection between pain nerves and scarring in adenomyosis, suggesting the pain itself may be driving disease progression. More importantly, it identifies rimegepant — already FDA-approved for migraines — as a potential nonhormonal treatment option, which is especially significant for women of reproductive age who want to preserve fertility.","specificNumbers":"","methodology":"The researchers combined human tissue analysis from adenomyosis patients with mouse models of induced adenomyosis. They examined nociceptive nerve density and CGRP expression in fibrotic lesions, performed nerve ablation experiments, characterized fibroblast subtypes using surface markers (CD140b and CD146), and tested the ERK signaling pathway's role. They then treated mice with rimegepant to assess its effects on fibrosis and fertility.","limitations":"The therapeutic results come from mouse models, and it remains to be seen whether rimegepant achieves similar anti-fibrotic effects in human adenomyosis patients. The study does not report specific quantitative measures of fibrosis reduction or fertility rates. Clinical trials would be needed to establish dosing, efficacy, and safety for this new indication."},{"rthcId":"RPEP-14368","title":"Lowly Expressed Toxin Transcripts in Poorly Characterized Myanmar Russell's Viper Venom Gland.","authors":"Yee, Khin Than; Macrander, Jason; Vasieva, Olga; Rojnuckarin, Ponlapat","year":2025,"journal":"Biotech (Basel (Switzerland)), 14(4)","doi":"10.3390/biotech14040096","pmid":"41440175","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14369","title":"Complexity of metabolic dysfunction-associated steatotic liver disease: State of the art review.","authors":"Yeh, Hsiao-Yun; Lin, Shang-Wei; Shen, Hsiao-Chin; Li, Tzu-Hao; Tsai, Hung-Cheng; Yang, Ying-Ying; Lin, Han-Chieh; Hou, Ming-Chih","year":2025,"journal":"Journal of the Chinese Medical Association : JCMA, 88(9), 662-671","doi":"10.1097/JCMA.0000000000001254","pmid":"40506815","tags":[],"studyType":"Review","evidenceStrength":"moderate","keyFinding":"The treatment landscape for metabolic dysfunction-associated steatotic liver disease (MASLD, formerly NAFLD) and its inflammatory progression to MASH (formerly NASH) is rapidly evolving, with peptide-based drugs playing a central role. GLP-1 receptor agonists, GLP-1/GIP dual agonists, and GIP/GLP-1/glucagon triple agonists are all being investigated as treatments that could halt or reverse liver disease progression.\n\nThese peptide therapies join other emerging drug classes including thyroid hormone receptor β agonists (recently approved), FXR agonists, and PPAR agonists. The review emphasizes that MASLD is a complex, multi-pathway disease involving insulin resistance, oxidative stress, gut-liver axis dysfunction, and genetic/epigenetic factors. When MASLD progresses unchecked, it can lead to cirrhosis and hepatocellular carcinoma (liver cancer). Lifestyle interventions remain foundational, but pharmacological options — particularly peptide-based ones — offer new hope for the large population affected.","whyItMatters":"MASLD affects roughly 25-30% of the global population and is becoming the leading cause of liver transplantation. Until very recently, there were no approved drug treatments. GLP-1 agonists and multi-agonist peptides represent some of the most promising pharmacological approaches because they address the metabolic root causes — insulin resistance, obesity, and inflammation — rather than just the liver symptoms.","specificNumbers":"MASLD affects ~25-30% of adults globally · Can progress to MASH → cirrhosis → liver cancer · GLP-1, GLP-1/GIP, and GLP-1/GIP/glucagon agonists under investigation · THR-β agonist newly approved","methodology":"State-of-the-art narrative review published in the Journal of the Chinese Medical Association, covering diagnosis, treatment (lifestyle, pharmacological, surgical), and the MASLD-to-HCC progression pathway. Surveys emerging drug classes with emphasis on peptide-based therapies.","limitations":"Narrative review without systematic methodology. Published in a regional medical journal with limited impact factor. Does not provide detailed efficacy data for specific peptide drugs or head-to-head comparisons. The rapidly evolving nature of MASLD therapeutics means some information may become outdated quickly."},{"rthcId":"RPEP-14370","title":"Association of SGLT2 inhibitors and GLP-1 receptor agonists with the risk of Parkinson's disease in patients with type 2 diabetes: A propensity score-matched cohort study with meta-analysis.","authors":"Yeh, Jia-Ai; Lin, Shu-Man; Liu, Yu-Chang; Hsu, Ji-Ze; Huang, Amy Huaishiuan; Munir, Kashif M; Peng, Carol Chiung-Hui; Loh, Ching-Hui; Huang, Huei-Kai","year":2025,"journal":"Diabetes research and clinical practice, 229, 112914","doi":"10.1016/j.diabres.2025.112914","pmid":"40976497","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14371","title":"GLP-1 Receptor Agonists Associated With Improved Survival After Infrainguinal Bypass in Diabetic Patients.","authors":"Yehualashet, Elonay; Mazroua, Muhammad S; Narvaez, Estefania; Jarosinski, Marissa C; Liang, Nathan L; Madigan, Michael C; Chaer, Rabih A; Sridharan, Natalie D","year":2025,"journal":"Annals of vascular surgery, 121, 480-491","doi":"10.1016/j.avsg.2025.08.013","pmid":"40825437","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14372","title":"Comparative risk of rheumatoid arthritis between glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors in type 2 diabetes.","authors":"Yen, Fu-Shun; Wang, Shiow-Ing; Hwu, Chii-Min; Huang, Chien-Wei; Chang, Renin; Hsu, Chih-Cheng; Wei, James Cheng-Chung","year":2025,"journal":"Journal of autoimmunity, 157, 103493","doi":"10.1016/j.jaut.2025.103493","pmid":"41110425","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14373","title":"Impact of Adding GLP-1 Receptor Agonists to Insulin Therapy on Cardiovascular and Microvascular Outcomes in Type 2 Diabetes: A Nationwide Cohort Study from Taiwan.","authors":"Yen, Fu-Shun; Wei, James Cheng-Chung; Sung, Chen-Yu; Li, Pei-Yun; Tsai, Fuu-Jen; Hsu, Chih-Cheng; Hwu, Chii-Min","year":2025,"journal":"Pharmaceuticals (Basel, Switzerland), 18(9)","doi":"10.3390/ph18091368","pmid":"41011236","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14374","title":"Impact of glucagon-like peptide-1 receptor agonists on the incidence of inflammatory bowel disease in people with type 2 diabetes.","authors":"Yen, Fu-Shun; Wang, Shiow-Ing; Hung, Yao-Min; Hsu, Chih-Cheng; Hwu, Chii-Min; Wei, James C-C","year":2025,"journal":"Diabetes, obesity & metabolism, 27(11), 6403-6415","doi":"10.1111/dom.70034","pmid":"40859767","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14375","title":"Subcellular interactions of neuropeptide Y and corticotropin-releasing factor in the central nucleus of the amygdala in the mouse.","authors":"Yerraguntla, Himavarsha; Onyekachi, Joy; Giacometti, Laura L; Goldberg, Samuel L; Barson, Jessica R; Barker, Jacqueline M; Reyes, Beverly A S","year":2025,"journal":"bioRxiv : the preprint server for biology","doi":"10.1101/2025.09.19.677477","pmid":"41000846","tags":[],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"For the first time, researchers provided ultrastructural evidence that neuropeptide Y (NPY) nerve terminals make direct synaptic contact with corticotropin-releasing factor (CRF) neurons in the central nucleus of the amygdala (CeA). Of 163 NPY terminals analyzed, approximately 85% formed symmetric (inhibitory) synapses with CRF dendrites, while only ~1% formed asymmetric (excitatory) synapses.\n\nThis anatomical wiring diagram reveals the physical basis for how NPY — the brain's 'stress resilience' peptide — may counteract CRF, the peptide that orchestrates the stress response. The overwhelming predominance of inhibitory-type connections suggests NPY primarily dampens CRF neuron activity.","whyItMatters":"The balance between NPY (calming) and CRF (stress-activating) in the amygdala is thought to determine stress resilience vs. vulnerability. When this balance tips toward CRF, it may contribute to anxiety, PTSD, and alcohol use disorders. This study provides the first anatomical proof that NPY directly synapses onto CRF neurons — confirming that the interaction is a direct neural circuit, not just a general chemical influence. This specificity matters for developing targeted treatments.","specificNumbers":"163 NPY terminals analyzed · ~85% form symmetric (inhibitory) synapses with CRF dendrites · ~1% form asymmetric (excitatory) synapses · Central nucleus of amygdala (CeA) · Mouse brain","methodology":"Researchers used two complementary microscopy techniques on mouse brain tissue: immunofluorescence microscopy to visualize NPY-labeled processes contacting CRF neurons, and electron microscopy with dual labeling (immunoperoxidase for NPY, gold-silver for CRF) to identify the exact synaptic connections at ultrastructural resolution. Semi-quantitative analysis classified synapse types.","limitations":"This is a preprint (bioRxiv) that has not yet undergone peer review. The study is purely anatomical — it shows physical connections but doesn't demonstrate functional inhibition of CRF neurons by NPY at these synapses. The mouse amygdala may differ from the human amygdala. The sample involved a limited number of animals (not specified)."},{"rthcId":"RPEP-14376","title":"Online Information About Side Effects and Safety Concerns of Semaglutide: Mixed Methods Study of YouTube Videos.","authors":"Yeung, Andy Wai Kan; Hammerle, Fabian Peter; Behrens, Sybille; Matin, Maima; Mickael, Michel-Edwar; Litvinova, Olena; Parvanov, Emil D; Kletecka-Pulker, Maria; Atanasov, Atanas G","year":2025,"journal":"JMIR infodemiology, 5, e59767","doi":"10.2196/59767","pmid":"40198905","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14377","title":"Diagnostic and Prognostic Evaluation of Novel Biomarkers Compared to ESC 0/1 h and 0/3 h Algorithms in Patients with Suspected Non-ST-Elevation Myocardial Infarction.","authors":"Yildirim, Mustafa; Salbach, Christian; Mueller-Hennessen, Matthias; Frey, Norbert; Giannitsis, Evangelos","year":2025,"journal":"Journal of clinical medicine, 14(9)","doi":"10.3390/jcm14092957","pmid":"40363990","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14378","title":"GLP-1 receptor agonists show no detrimental effect on sperm quality in mouse models and cell lines.","authors":"Yin, Deshan; Li, Fei; Xia, Li; Wei, Tianjiao; Shan, Chunhua; Zhang, Zhe; Wei, Rui","year":2025,"journal":"Endocrine, 89(2), 614-626","doi":"10.1007/s12020-025-04245-4","pmid":"40347306","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14379","title":"The clinical value of α-hydroxybutyrate dehydrogenase, cardiac troponin I, and B-type natriuretic peptide in perioperative diagnosis of heart failure in children with congenital heart disease.","authors":"Yin, Jun; Wang, Qingsong; Xu, Shuqiong; Wang, Junru; Huang, Shihua; Shen, Junhong; Yuan, Tao; Luo, Tongyong; Wang, Xianmin","year":2025,"journal":"Frontiers in pediatrics, 13, 1502439","doi":"10.3389/fped.2025.1502439","pmid":"40051908","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14380","title":"Nanoshield Architecture Harnessing Neoantigen-Targeting Peptides Enables Durable Post-surgical Glioma Immunotherapy.","authors":"Yin, Qiliang; Li, Jingjing; Zhang, Jianhua; Leng, Jiyan; Zhang, Kexin; Gao, Xihui; Wang, Fan; Yue, Qi; Ma, Chao; Xu, Huaping; Liu, Xiaogang; Zhang, Hongjie; Liu, Kai","year":2025,"journal":"Nano letters, 25(36), 13629-13638","doi":"10.1021/acs.nanolett.5c03459","pmid":"40859665","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14381","title":"Efficacy of GLP-1 Receptor Agonist-Based Therapies on Cardiovascular Events and Cardiometabolic Parameters in Obese Individuals Without Diabetes: A Meta-Analysis of Randomized Controlled Trials.","authors":"Yin, Yue; Zhang, Minghan; Cao, Qiuyu; Lin, Lin; Lu, Jieli; Bi, Yufang; Chen, Yuhong","year":2025,"journal":"Journal of diabetes, 17(4), e70082","doi":"10.1111/1753-0407.70082","pmid":"40207414","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Pooled analysis of 29 RCTs (37,348 participants, 9 GLP-1RA-based drugs) in non-diabetic overweight/obese adults found:\n\n**Cardiovascular Outcomes (vs. placebo):**\n- Total cardiovascular events: RR 0.81 (95% CI: 0.76-0.87) — 19% reduction\n- Major adverse cardiovascular events (MACE): RR 0.80 (0.72-0.89) — 20% reduction\n- Myocardial infarction: RR 0.72 (0.61-0.85) — 28% reduction\n- All-cause mortality: RR 0.81 (0.71-0.93) — 19% reduction\n- Cardiovascular death: no significant difference\n- Stroke: no significant difference\n\n**Best-in-class for cardiometabolic parameters:**\n- Systolic blood pressure: Orforglipron (-7.10 mmHg)\n- BMI reduction: Tirzepatide (-6.50 kg/m²)\n- HbA1c reduction: Tirzepatide (-0.39%)\n- Lipid profiles: Retatrutide (most effective)\n- C-reactive protein: Semaglutide (-1.20 mg/dL)","whyItMatters":"Until recently, the cardiovascular benefits of GLP-1 medications were only proven in people with diabetes. This meta-analysis demonstrates that these drugs also protect the heart in non-diabetic obese individuals — expanding the potential beneficiaries to hundreds of millions of people worldwide. The head-to-head drug comparisons also provide practical guidance for clinicians choosing between different GLP-1 medications based on each patient's specific risk profile.","specificNumbers":"","methodology":"Systematic meta-analysis of RCTs searched across PubMed, Embase, Cochrane, and Web of Science (through June 2024). Inclusion criteria: randomized controlled trials in non-diabetic adults with overweight/obesity comparing GLP-1RA-based therapies to placebo, reporting cardiovascular events and metabolic parameters. 29 RCTs with 9 different drugs and 37,348 participants were included. Relative risks and mean differences were calculated with 95% confidence intervals.","limitations":"While the overall sample is large (37,348), the cardiovascular event data are likely driven primarily by a few large trials (particularly SELECT). Some of the 9 drugs included had limited trial data. Stroke and cardiovascular death did not show significant reductions, which may reflect insufficient power or a true lack of effect. Follow-up durations varied across trials. The analysis includes both single GLP-1 agonists and dual/triple agonists, which may have different mechanisms. Publication bias was not explicitly addressed in the abstract."},{"rthcId":"RPEP-14382","title":"Elephant Cathelicidin-Derived Peptides Inhibit Herpes Simplex Virus 1 Infection.","authors":"Yisihaer, Haiche; Dong, Peng; Li, Pengpeng; Deng, Enjie; Meng, Rui; Jin, Lin; Li, Guilan","year":2025,"journal":"Antibiotics (Basel, Switzerland), 14(7)","doi":"10.3390/antibiotics14070655","pmid":"40723958","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Four peptides (EM-1 through EM-4) were designed from Asian elephant (Elephas maximus) cathelicidin EM. EM-1 demonstrated the best profile: low hemolytic and cytotoxicity, with significant inhibition of HSV-1 replication in U251 cells.\n\nIn C57BL/6J mice infected via footpad inoculation, EM-1 substantially reduced viral loads in brain, lung, and heart tissues and alleviated inflammatory responses and tissue damage. Mechanistically, EM-1 upregulated interferon-gamma expression and downstream antiviral genes ISG15 and MX1, revealing a dual-function profile: direct antiviral activity plus enhancement of host innate immunity.","whyItMatters":"HSV-1 infects an estimated 3.7 billion people globally, and current antivirals like acyclovir cannot address viral latency or prevent recurrence. New antiviral approaches are urgently needed. Animal-derived antimicrobial peptides represent a largely untapped source of antiviral candidates, and the dual mechanism of EM-1 — directly fighting the virus while boosting immune defenses — is particularly attractive because it could reduce the chance of drug resistance.","specificNumbers":"","methodology":"Four peptides derived from elephant cathelicidin were designed and optimized. Safety was assessed through hemolytic and cytotoxicity assays. Antiviral activity was measured by IC50 determination against HSV-1 in U251 (human glioma) cells. Mechanisms were investigated using RT-qPCR for gene expression. In vivo validation used C57BL/6J mice with footpad HSV-1 inoculation, measuring viral loads in brain, lung, and heart, plus histological assessment of tissue damage.","limitations":"This was a preclinical study using cell lines and mouse models. The mouse footpad HSV-1 model, while established, doesn't fully recapitulate human herpes infection patterns including latency in ganglia and reactivation. IC50 values for EM-1 were not specified in the abstract. The pharmacokinetics, stability, and optimal dosing route for EM-1 in vivo were not characterized. The study used U251 glioma cells rather than more physiologically relevant epithelial cells for in vitro testing."},{"rthcId":"RPEP-14383","title":"Impact of degradation in subcutaneous tissue and lymphatic fluid on absorption of Fc-fusion proteins following subcutaneous administration.","authors":"Yokoyama, Miki; Suzuki, Eiko; Nakai, Daisuke","year":2025,"journal":"Drug metabolism and pharmacokinetics, 64, 101500","doi":"10.1016/j.dmpk.2025.101500","pmid":"40912139","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14384","title":"Do Incretin-Based Therapies Influence the Risk of Cholangiocarcinoma in Type 2 Diabetes Patients? Insights from a Systematic Review and Meta-Analysis.","authors":"Yonatan, Eric Ricardo; Jusni, Louis Fabio Jonathan; Alvianto, Steven; Widjanarko, Nicolas Daniel; Usman, Steven Yulius; Muzellina, Virly Nanda","year":2025,"journal":"Journal of gastrointestinal cancer, 56(1), 198","doi":"10.1007/s12029-025-01330-9","pmid":"41075111","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across four observational studies (three cohort, one case-control):\n\n- GLP-1 receptor agonists: pooled HR 1.07 (95% CI: 0.70–1.63) — no significant association with cholangiocarcinoma\n- DPP-4 inhibitors: pooled HR 1.05 (95% CI: 0.83–1.34) — no significant association\n- Pooled risk ratio analyses yielded similarly non-significant results for both drug classes\n- All included studies were assessed as having low risk of bias per the Newcastle-Ottawa Scale\n- Findings provide reassurance about the safety of incretin-based therapies regarding bile duct cancer risk","whyItMatters":"With millions of people now taking GLP-1 drugs for diabetes and obesity, understanding their cancer risk profile is critical. Cholangiocarcinoma is a rare but aggressive cancer, and even a small increase in risk would affect many people at population level. This meta-analysis provides early reassurance that incretin-based therapies don't appear to increase this particular cancer risk.","specificNumbers":"","methodology":"Systematic review and meta-analysis following PRISMA 2020 guidelines, registered in PROSPERO. Databases searched included PubMed, ProQuest, EBSCOhost, Wiley, and SAGE. Four eligible observational studies were included. Study quality was assessed using the Newcastle-Ottawa Scale. Pooled hazard ratios and risk ratios with 95% CIs were calculated using a random-effects model.","limitations":"Only four observational studies were available, limiting statistical power. Observational studies cannot establish causation. The relatively rare incidence of cholangiocarcinoma means even pooled data may be insufficient to detect small risk increases. Follow-up periods may have been too short to capture cancers with long latency periods. The analysis didn't distinguish between different GLP-1 RAs or DPP-4 inhibitors."},{"rthcId":"RPEP-14385","title":"Antimicrobial peptides and proteins in Alzheimer's and Parkinson's diseases: implications for biomarker exploration.","authors":"Yong, Shin Jie; Teoh, Seong Lin; Parhar, Ishwar S; Soga, Tomoko; Lim, Wei Ling; Chew, Jactty","year":2025,"journal":"Reviews in the neurosciences, 36(8), 849-879","doi":"10.1515/revneuro-2025-0034","pmid":"40513579","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14386","title":"Obesity and the Genome: Emerging Insights from Studies in 2024 and 2025.","authors":"Yoo, Lindsey G; Bordelon, Courtney L; Mendoza, David; Stephens, Jacqueline M","year":2025,"journal":"Genes, 16(9)","doi":"10.3390/genes16091015","pmid":"41009961","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14387","title":"Exendin-4(1-32)K-Capric Acid, a Glucagon-Like Peptide-1 Receptor Agonist, Suppresses Food Intake via Arcuate Pro-Opiomelanocortin Neurons.","authors":"Yoo, Sujin; Yoo, Eun-Seon; Kim, Jae Il; Sohn, Jong-Woo","year":2025,"journal":"Endocrinology and metabolism (Seoul, Korea), 40(3), 434-447","doi":"10.3803/EnM.2024.2185","pmid":"40223290","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14388","title":"GLP-1RA Reduces Supraspinatus Fatty Infiltration and Promotes Functional Recovery in a Rat Model of Rotator Cuff Repair.","authors":"Yoon, Jong Pil; Park, Sung-Jin; Kim, Dong-Hyun; Choi, Yoon Seong; Lee, Hyun Joo; Kim, Jun-Young; Cho, Chul-Hyun; Chung, Seok Won","year":2025,"journal":"The American journal of sports medicine, 53(12), 2973-2983","doi":"10.1177/03635465251369517","pmid":"40938084","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14389","title":"Comparison of Natriuretic Peptide Levels in Sinus Rhythm and Atrial Fibrillation in Acute Heart Failure.","authors":"Yoon, Minjae; Park, Jin Joo; Youn, Jong-Chan; Lee, Sang Eun; Lee, Hae-Young; Choi, Jin Oh; Kim, Kye Hun; Yang, Dong Heon; Cho, Myeong-Chan; Kang, Seok-Min; Yoo, Byung-Su","year":2025,"journal":"International journal of heart failure, 7(2), 85-95","doi":"10.36628/ijhf.2025.0007","pmid":"40519716","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14390","title":"Aortic Regurgitation Jet Increases Left Ventricular Energy Loss Associated With the Progression of Cardiac Failure　- A Vector Flow Mapping Analysis Study.","authors":"Yoshida, Shohei; Toda, Koichi; Yoshikawa, Yasushi; Hata, Hiroki; Yoshioka, Daisuke; Kainuma, Satoshi; Kawamura, Takuji; Kawamura, Ai; Inoue, Koichi; Kakizawa, Yumi; DeRoo, Scott; Burke, Christopher R; Nakatani, Satoshi; Shimamura, Kazuo; Sawa, Yoshiki; Miyagawa, Shigeru","year":2025,"journal":"Circulation journal : official journal of the Japanese Circulation Society","doi":"10.1253/circj.CJ-24-0965","pmid":"40790799","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14391","title":"Peptides as functional excipients for drug delivery.","authors":"Yoshida, Takayuki; Kojima, Hiroyuki","year":2025,"journal":"European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 216, 114856","doi":"10.1016/j.ejpb.2025.114856","pmid":"40907835","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14392","title":"Effects of Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors on Relationship Between B-Type Natriuretic Peptide and Hemoglobin Levels in Patients With Cardiorenal Anemia Syndrome.","authors":"Yoshitake, Tomoaki; Hashimoto, Toru; Matsushima, Shouji; Ikuta, Kei; Yamamoto, Shoei; Suenaga, Tomoyasu; Nakashima, Shunsuke; Kai, Takashi; Misumi, Kayo; Shinohara, Keisuke; Fujino, Takeo; Katsuki, Shunsuke; Hosokawa, Kazuya; Kinugawa, Shintaro; Abe, Kohtaro","year":2025,"journal":"Cardiovascular therapeutics, 2025, 3143864","doi":"10.1155/cdr/3143864","pmid":"41244933","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14393","title":"Development of NAFLD-Specific Human Liver Organoid Models on a Microengineered Array Chip for Semaglutide Efficacy Evaluation.","authors":"You, Xiao-Yan; Li, Xiang-Yang; Wang, Hui; Zhao, Guo-Ping","year":2025,"journal":"Cell proliferation, e70118","doi":"10.1111/cpr.70118","pmid":"40873114","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14394","title":"Glucagon-Like Peptide-1 (GLP-1) Receptor Agonist Use and Inflammatory Markers Among U.S. Adults: A National Health and Nutrition Examination Survey (NHANES)-Based Analysis.","authors":"Youkhana, Sharokeen; Odusanmi, Seun S; Ihuchukwu, Bruno K; Ezekiel, Mathew; Enyeneokpon, Edidiong; Cumaaran, Christina; Akpamgbo, Emmanuel O; Okobi, Okelue E","year":2025,"journal":"Cureus, 17(8), e90964","doi":"10.7759/cureus.90964","pmid":"41001317","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14395","title":"Mobile App-Based Interactive Care Plan for Migraine: Survey Study of Usability and Improvement Opportunities.","authors":"Young, Nathan P; Stern, Jennifer I; Steel, Stephanie J; Ebbert, Jon O","year":2025,"journal":"JMIR formative research, 9, e66763","doi":"10.2196/66763","pmid":"40143383","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14396","title":"Self-Assembled Peptide-Based Fibrous Hydrogel as a Biological Catalytic Scaffold for Nitric Oxide Generation and Encapsulation.","authors":"Younis, Muhammad; Tabish, Tanveer A; Firdharini, Cherly; Aslam, Mohamed; Khair, Mostafa; Anjum, Dalaver H; Yan, Xuehai; Abbas, Manzar","year":2025,"journal":"ACS applied materials & interfaces, 17(19), 27964-27973","doi":"10.1021/acsami.5c03250","pmid":"40301105","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14397","title":"Are GLP-1 Receptor Agonists Safe in Spine Surgery: A Systematic Review.","authors":"Younus, Iyan; Garcia de Oliveira, Rafael; Fujii, Takeshi; Bansal, Aiyush; Lipson, Patricia; Sethi, Rajiv; Nemani, Venu M; Leveque, Jean-Christophe; Louie, Philip K","year":2025,"journal":"Spine","doi":"10.1097/BRS.0000000000005466","pmid":"40719010","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14398","title":"Effects of Dichrostachys glomerata and Cissus quadrangularis Extracts on GLP-1 Secretion and DPP-4 Activity in Overweight and Obese Individuals: A Randomized Controlled Trial.","authors":"Youovop, Janvier; Takuissu, Guy; Minoue, Régine; Nwang, Felix; Adegboyega, Maryam; Arrey, Crista; Makamwe, Inelle; Oben, Julius","year":2025,"journal":"Medicina (Kaunas, Lithuania), 62(1)","doi":"10.3390/medicina62010041","pmid":"41597327","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14399","title":"Protective anti-fibrotic effect of liraglutide and Pirfenidone combination therapy on liver fibrosis in rats: effects on autophagy and NLRP3 inflammasome.","authors":"Yousefi, Zeynab; Rajabi, Rayan; Karima, Saeed; Nourbakhsh, Mitra; Lotfi, Abbas Sahebghadam","year":2025,"journal":"BMC gastroenterology, 26(1), 57","doi":"10.1186/s12876-025-04545-z","pmid":"41413484","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14400","title":"A highly efficient method for screening dual-target inhibitory peptides against angiotensin I-converting enzyme and α-amylase from Chlorella using an enzyme-immobilized affinity membrane.","authors":"Yu, Cailing; Zu, Xinyu; Liang, Yan; Zhao, Xiangzhong; Li, Yingqiu; Wang, Chenying; Wang, Hua","year":2025,"journal":"International journal of biological macromolecules, 333(Pt 1), 148954","doi":"10.1016/j.ijbiomac.2025.148954","pmid":"41224052","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14401","title":"Impact of monotherapy and combination therapy with glucagon-like peptide-1 receptor agonists on exosomal and non-exosomal MicroRNA signatures in type 2 diabetes mellitus: a systematic review.","authors":"Yu, Haifeng; Davoudi, Maryam; Sadegh-Nejadi, Sahar; Miao, Xiaolei; Bagherieh, Molood; Afrisham, Reza","year":2025,"journal":"Journal of translational medicine, 23(1), 477","doi":"10.1186/s12967-025-06461-y","pmid":"40281607","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14402","title":"Comparison of PET/CT using 68Ga-NOTA-Exendin-4 with 68Ga-DOTATATE, 18F-FDG, and conventional imaging in the localization of insulinomas.","authors":"Yu, Haonan; Bao, Xiangyuan; Gu, Yian; Pan, Meijie; He, Qing; Li, Dong; Chen, Qiusong; Yao, Shaobo","year":2025,"journal":"European journal of nuclear medicine and molecular imaging, 52(11), 4102-4111","doi":"10.1007/s00259-025-07288-x","pmid":"40259061","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 47 patients with biochemically proven hyperinsulinemic hypoglycemia, the peptide-based tracer 68Ga-NOTA-Exendin-4 PET/CT achieved 94.11% sensitivity and 95.74% accuracy for localizing insulinomas — significantly outperforming 68Ga-DOTATATE PET/CT (70.59% sensitivity, p=0.026), 18F-FDG PET/CT (50.00% sensitivity), and conventional imaging (CE-CT/CE-MRI).\n\nExendin-4 PET/CT also showed better imaging quality and easier interpretation than the other molecular imaging methods. Combining Exendin-4 and DOTATATE PET/CT could provide comprehensive evaluation of insulinomas.","whyItMatters":"Insulinomas are rare pancreatic tumors that cause dangerous low blood sugar. Finding them before surgery is critical but difficult — conventional imaging often misses them. This peptide-based imaging approach nearly doubles the detection rate compared to standard PET tracers, potentially transforming how these tumors are located and treated.","specificNumbers":"","methodology":"A prospective study of 47 patients with biochemically confirmed endogenous hyperinsulinemic hypoglycemia. All patients underwent 68Ga-NOTA-Exendin-4 PET/CT alongside other imaging methods (68Ga-DOTATATE PET/CT, 18F-FDG PET/CT, CE-CT, CE-MRI). Sensitivity and accuracy were calculated at both patient and lesion levels. Both experienced (>10 years) and junior radiologists interpreted the scans to assess interpretability.","limitations":"Relatively small sample of 47 patients, though insulinomas are rare. The study was retrospectively registered on ClinicalTrials.gov. 68Ga-NOTA-Exendin-4 is not yet widely available, limiting immediate clinical applicability. Results may not generalize to malignant insulinomas, as the study focused on benign tumors."},{"rthcId":"RPEP-14403","title":"Effects of GHRH and its analogues on the Vascular System.","authors":"Yu, Hong; Peng, Huan","year":2025,"journal":"Reviews in endocrine & metabolic disorders, 26(3), 493-505","doi":"10.1007/s11154-024-09932-7","pmid":"39570567","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14404","title":"Pharmacokinetic-pharmacodynamic (PK/PD) modelling of cotadutide effect in patients with chronic kidney disease and type 2 diabetes mellitus.","authors":"Yu, Hongtao; Parker, Victoria; Selvarajah, Viknesh; Hansen, Lars; Robertson, Darren; Hamrén, Bengt; Khan, Anis; Parkinson, Joanna","year":2025,"journal":"British journal of clinical pharmacology, 91(9), 2672-2683","doi":"10.1002/bcp.70093","pmid":"40344607","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14405","title":"Nmnat2 deficiency in the arcuate nucleus or paraventricular nucleus induces Sarm1-independent neuron loss and liraglutide-reversible obesity.","authors":"Yu, Huimin; Feng, Ning; Zhong, Wuling; Han, Yumo; Cheng, Yalan; Zhang, Zhentong; Wang, Yingqi; Gao, Peidong; Huang, Rui; Zhang, Cong; Liu, Zongyang; Dong, Jieya; He, Zhishui; Lai, Hejin; Shen, Ziru; Zhai, Qiwei","year":2025,"journal":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 39(4), e70400","doi":"10.1096/fj.202402546R","pmid":"39964232","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14406","title":"Hypofractionated radiotherapy combined with a PD-1 inhibitor, granulocyte macrophage-colony stimulating factor, and thymosin-α1 in advanced metastatic solid tumors: a multicenter Phase II clinical trial.","authors":"Yu, Jiamin; Yin, Li; Guo, Wenjie; Wang, Qiang; Liu, Juying; Zhang, Lansheng; Ye, Hongxun; Xia, Jianhong; Xia, Youyou; Wu, Jianfeng; Wang, Wanwei; Yang, Yanguang; Zong, Dan; He, Xia; Wang, Lijun; Jiang, Hong","year":2025,"journal":"Cancer immunology, immunotherapy : CII, 74(3), 98","doi":"10.1007/s00262-024-03934-9","pmid":"39904914","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In this Phase II trial, combining hypofractionated radiotherapy with PD-1 inhibitor immunotherapy, GM-CSF, and the peptide thymosin-α1 achieved a 23.08% objective response rate and 65.38% disease control rate in heavily pretreated metastatic cancer patients. Median progression-free survival was 3.5 months. Notably, abscopal effects (tumor shrinkage at sites not directly irradiated) were observed in 23.08% of patients, with four achieving partial responses. Lower baseline neutrophil-to-lymphocyte ratio predicted better outcomes. The regimen was manageable with six grade 3-4 adverse events and no treatment-related deaths.","whyItMatters":"Patients with heavily treated metastatic solid tumors have few remaining options. This trial demonstrates that adding the immunomodulatory peptide thymosin-α1 to a radiation-immunotherapy combination can produce meaningful responses including abscopal effects — where distant tumors shrink from local radiation combined with systemic immune activation. This suggests thymosin-α1 enhances the immune priming effect.","specificNumbers":"n=37 · 23.08% ORR · 65.38% DCR · median PFS 3.5 months · 23.08% abscopal effects · 6 grade 3-4 AEs · 0 grade 5 AEs · median follow-up 5.97 months","methodology":"Multicenter Phase II trial enrolling patients with heavily treated metastatic solid tumors from September 2022 to May 2024. Treatment: HFRT to targeted tumors + GM-CSF for 14 days from day 1 + thymosin-α1 twice weekly until progression + camrelizumab (PD-1 inhibitor) every 3 weeks after HFRT. Endpoints included PFS, ORR, DCR, abscopal effects, and safety. Analysis by intention-to-treat.","limitations":"Small sample size (37 patients) in a single-arm Phase II trial without a control group. Overall survival data not yet mature. Median follow-up of only 5.97 months is short. Cannot determine the individual contribution of thymosin-α1 versus the other components. Heterogeneous tumor types may complicate interpretation."},{"rthcId":"RPEP-14407","title":"Clusterin protects against HFpEF by inhibiting UCHL1-mediated NLRP3 deubiquitylation and inflammasome activation.","authors":"Yu, Jiangling; Kang, Xiaoxu; Chang, Rui; Zhang, Cheng; Yang, Song; Chen, Lang; Wang, Xinbo; Hu, Bing; Wang, Zixuan; Gong, Lili; Liu, Lihong","year":2025,"journal":"Frontiers in pharmacology, 16, 1704023","doi":"10.3389/fphar.2025.1704023","pmid":"41608024","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14408","title":"Exploring the mechanism of Qiling Jiaogulan Powder in protecting heart injury of heat-stressed broilers based on transcriptome.","authors":"Yu, Juan; Wang, Qing; Xu, Min; Wang, Shangbin; Xu, Yanzhao; He, Hongxuan","year":2025,"journal":"Poultry science, 104(12), 105962","doi":"10.1016/j.psj.2025.105962","pmid":"41092608","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14409","title":"Structured design colon-targeted nanoparticles with different distribution ratios of lecithin inside and outside starch helical cavity for enhancing GLP-1 secretion.","authors":"Yu, Mengting; Chi, Chengdeng; Huang, Shuangxia; Li, Xiaoxi","year":2025,"journal":"Food chemistry, 495(Pt 2), 146439","doi":"10.1016/j.foodchem.2025.146439","pmid":"41016292","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14410","title":"iGlarLixi: A titrateable fixed-ratio combination of basal insulin + GLP-1 receptor agonist-An effective type 2 diabetes treatment option in China.","authors":"Yu, Miao","year":2025,"journal":"Diabetes, obesity & metabolism, 27 Suppl 10(Suppl 10), 15-23","doi":"10.1111/dom.70192","pmid":"41116700","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14411","title":"MicroRNA-34a-5p regulates agouti-related peptide via krüppel-like factor 4 and is disrupted by bisphenol A in hypothalamic neurons.","authors":"Yu, Minyi; He, Wenyuan; Belsham, Denise D","year":2025,"journal":"Gene, 937, 149129","doi":"10.1016/j.gene.2024.149129","pmid":"39617277","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14412","title":"Efficacy and Safety of Electroacupuncture for Postherpetic Neuralgia and Biomarker Evaluation: A Study Protocol for a Multicenter, Randomized Trial.","authors":"Yu, Qintao; Wang, Xinru; Wu, Jiaqi; Zhang, Qiyuan; Ying, Xiaoqi; Ou, Liming; Hu, Hantong; He, Kelin; Wu, Lei; Jin, Zongda; Shentu, Jiajun; Dai, Huifeng; Ma, Ruijie; Hu, Qimiao; Han, Dexiong","year":2025,"journal":"Journal of pain research, 18, 5753-5768","doi":"10.2147/JPR.S559309","pmid":"41199896","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14413","title":"Inhaled exogenous thymosin beta 4 suppresses bleomycin-induced pulmonary fibrosis in mice via TGF-β1 signalling pathway.","authors":"Yu, Rui; Li, Shimeng; Chen, Li; Hu, Enbo; Chai, Dan; Liu, Zhichao; Zhang, Qianyi; Mao, Yunyun; Zhai, Yanfang; Li, Kai; Liu, Yanhong; Li, Xiaohe; Zhou, Honggang; Yang, Cheng; Xu, Junjie","year":2025,"journal":"The Journal of pharmacy and pharmacology, 77(4), 582-592","doi":"10.1093/jpp/rgae143","pmid":"39579076","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14414","title":"Mitigating Trastuzumab-Doxorubicin Cardiotoxicity With Multiscale Quantitative Systems Toxicology and PBPK-Toxicodynamic Predictive Modeling Framework.","authors":"Yu, Sijia; Mody, Hardik; Vaidya, Tanaya R; Kagan, Leonid; Ait-Oudhia, Sihem","year":2025,"journal":"CPT: pharmacometrics & systems pharmacology, 14(10), 1625-1636","doi":"10.1002/psp4.70087","pmid":"40714937","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14415","title":"Association of tirzepatide and the risk of suicide in a real-world cohort.","authors":"Yu, Wei-Shin; Huang, Jing-Yang; Lo, Shih-Chang; Huang, Chien-Ning; Yang, Yi-Sun; Kornelius, Edy","year":2025,"journal":"Frontiers in psychiatry, 16, 1626103","doi":"10.3389/fpsyt.2025.1626103","pmid":"41334076","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14416","title":"Effects of Xuebijing combined with levosimendan on immune function and coagulation function in sepsis patients with myocardial injury.","authors":"Yu, Wenbo; Liu, Congnan; Zhou, Yingjie; Lin, Peng","year":2025,"journal":"Journal of thrombosis and thrombolysis","doi":"10.1007/s11239-025-03201-3","pmid":"41206374","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14417","title":"Multi-pathway-driven hepatic protection: Semaglutide combined with HIIT counteracts diabetic liver injury in db/db mice.","authors":"Yu, Wenjun; Liu, Yongfu; Le, Shenglong; Xiao, Yuxin; Chen, Xiaoyan; Wang, Junhua; Gao, Feng","year":2025,"journal":"Journal of diabetes investigation, 16(12), 2145-2159","doi":"10.1111/jdi.70174","pmid":"41065060","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14418","title":"Divergence and conservation of neuropeptide Y receptors in teleosts with diverse feeding habits.","authors":"Yu, Xiao-Zheng; Lu, Yi-Yao; Yu, Yang; Liu, Zi-Yan","year":2025,"journal":"Comparative biochemistry and physiology. Part D, Genomics & proteomics, 56, 101662","doi":"10.1016/j.cbd.2025.101662","pmid":"41124712","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14419","title":"Fatty acid metabolism after short-term fasting: POMC response and EPA signal maintain homeostasis in tilapia.","authors":"Yu, Xiaozheng; Zhu, Tiansheng; Yu, Yang; Cai, Ran; Li, Meiqing; Sun, Caiyun; Li, Wensheng","year":2025,"journal":"Frontiers in endocrinology, 16, 1585216","doi":"10.3389/fendo.2025.1585216","pmid":"40416526","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14420","title":"Neuropeptide Y Boosts Intestinal Mucosal Immunity of Tilapia Infected with Streptococcus agalactiae by Reducing Inflammation and Oxidative Stress.","authors":"Yu, Yang; Liu, Ziyan; Zhou, Mengyuan; Chen, Zexia; Cai, Ran; Song, Chaowei; Li, Meiqing; Zhu, Tiansheng; Sun, Caiyun; Li, Wensheng","year":2025,"journal":"Animals : an open access journal from MDPI, 15(18)","doi":"10.3390/ani15182730","pmid":"41007974","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14421","title":"Peptide based vesicles for cancer immunotherapy: design, construction and applications.","authors":"Yu, Yulin; Lyu, Jiaxin; Muhadaisi, Yizimujiang; Shi, Chen; Wang, Dongyuan","year":2025,"journal":"Frontiers in immunology, 16, 1609162","doi":"10.3389/fimmu.2025.1609162","pmid":"40496863","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14422","title":"Novel antidiabetic agents and the risk of respiratory diseases: a systematic review and meta-analysis of 27 randomized controlled trials.","authors":"Yu, Zhexuan; Gu, Bingyan; Zhang, Junyao; Jin, Weifeng; Wan, Haitong; Jin, Wei","year":2025,"journal":"Frontiers in medicine, 12, 1721311","doi":"10.3389/fmed.2025.1721311","pmid":"41567683","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 27 RCTs with 202,727 participants:\n\n**SGLT2 inhibitors** reduced risk of:\n- Pneumonia: OR 0.84 (16% reduction)\n- Bronchitis: OR 0.59 (41% reduction)\n- COPD: OR 0.76 (24% reduction)\n- Pulmonary edema: OR 0.51 (49% reduction)\n- Respiratory failure: OR 0.77 (23% reduction)\n- Asthma: OR 0.55 (45% reduction)\n\n**GLP-1 receptor agonists** were neutral in T2DM but reduced pneumonia, respiratory failure, and asthma risk in obese populations.\n\n**DPP-4 inhibitors** were largely neutral but increased asthma risk (OR 1.70, 70% increase).\n\nSGLT2 inhibitor benefits appeared largely independent of diabetes status.","whyItMatters":"This is the first comprehensive meta-analysis comparing three major diabetes drug classes for respiratory outcomes. The finding that GLP-1 RAs reduce respiratory disease risk specifically in obese populations is particularly relevant given the surging use of these peptide drugs for weight loss. It suggests that the lung benefits may be mediated by weight reduction or anti-inflammatory effects associated with GLP-1 signaling. The DPP-4 inhibitor asthma warning is also clinically important.","specificNumbers":"","methodology":"Systematic review and meta-analysis of 27 large randomized controlled trials, prospectively registered in PROSPERO. Both pairwise and network meta-analyses were performed to compare SGLT2 inhibitors, GLP-1 RAs, and DPP-4 inhibitors against placebo. Prespecified respiratory outcomes included pneumonia, bronchitis, COPD, pulmonary edema, pulmonary embolism, respiratory failure, and asthma. Subgroup analyses examined effects by diabetes status and obesity.","limitations":"The authors explicitly state these findings are hypothesis-generating and require validation. Respiratory outcomes were secondary endpoints in the included trials — none were designed to study lung diseases primarily. The distinction between GLP-1 RA effects in diabetic vs. obese populations may reflect differences in trial design rather than true biological differences. The DPP-4 inhibitor asthma finding is based on relatively few events and wide confidence intervals."},{"rthcId":"RPEP-14423","title":"Effect of Glucagon-Like Peptide-1 Receptor Agonists on Renal and Cardiovascular Risk Factors in Patients With Type 2 Diabetes Mellitus: A Retrospective Study.","authors":"Yuan, Daniel; Vangaveti, Venkat N; Arojojoye, Oluwatosin A; Malabu, Usman H","year":2025,"journal":"Journal of diabetes research, 2025, 2663671","doi":"10.1155/jdr/2663671","pmid":"41246137","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14424","title":"Improving Nutritional Status in Chronic Heart Failure Patients: Effectiveness of a Transtheoretical Model-Based Stepwise Nutritional Management Program.","authors":"Yuan, Dejing; Xue, Yuan; Zhou, Yuefei","year":2025,"journal":"Risk management and healthcare policy, 18, 1683-1695","doi":"10.2147/RMHP.S509402","pmid":"40416832","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14425","title":"Linoleic acid co-administration promotes oral delivery of exenatide-loaded butyrate-decorated nanocapsules.","authors":"Yuan, Haoyang; Xiao, Peifu; Wang, Fan; Guo, Chen; Pan, Shu; Jiang, Mai; Hou, Shicheng; Sun, Yunong; Wang, Yibo; Zhang, Yu; Yin, Tian; He, Haibing; Gou, Jingxin; Tang, Xing","year":2025,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 382, 113744","doi":"10.1016/j.jconrel.2025.113744","pmid":"40246242","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14426","title":"Identification of neoantigen epitopes in cervical cancer by multi-omics analysis.","authors":"Yuan, Jing; Xu, Na; Gong, Xueqi; Ai, Jihui; Li, Kezhen; Han, Yingyan","year":2025,"journal":"European journal of medical research, 30(1), 763","doi":"10.1186/s40001-025-03036-x","pmid":"40826144","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"From 284 cervical cancer samples, researchers identified 30 highly mutated genes and narrowed these to seven (TTN, PRKDC, PCLO, MUC17, HUWE1, RYR2, and CREBBP) that positively correlated with immune cell infiltration into tumors. PCLO stood out because it showed higher protein expression in tumor tissue versus normal tissue, marking it as a potential tumor antigen.\n\nUsing computational prediction algorithms (NetMHCpan-4.0 and NetCTL-1.2), two PCLO-derived peptides — SISRFTLEK (PCLOL4169F) and LSEAGHFFY (PCLOA3000S) — achieved the highest predicted immunogenicity scores. These peptides were validated experimentally: they activated T cells in vivo (confirmed by flow cytometry and RT-PCR) and stimulated immune responses in patient-derived peripheral blood mononuclear cells with matching HLA types in ELISpot assays.","whyItMatters":"Cervical cancer remains a major global health burden, and while HPV vaccines prevent new infections, they don't help patients with existing tumors — especially HPV-negative cases. Identifying neoantigen peptides that the immune system can target opens the door to therapeutic vaccines that could treat established cervical cancers by directing T cells to attack tumor-specific mutations.","specificNumbers":"","methodology":"The study used a computational pipeline analyzing TCGA data from 284 cervical cancer samples across three levels: genomic (mutation frequency), transcriptomic (immune cell infiltration via RNA-seq), and proteomic (protein expression). High-frequency mutations in genes correlated with immune infiltration were used to predict MHC class I neoantigen peptides via NetMHCpan-4.0 and NetCTL-1.2 algorithms. Top candidates were synthesized and validated experimentally using flow cytometry, real-time PCR for T cell activation markers, and ELISpot assays with patient PBMCs.","limitations":"The candidate neoantigens were identified primarily through computational analysis of TCGA data, and while experimentally validated, the validation was limited in scope. The study did not test whether these peptide vaccines could shrink tumors in animal models or clinical settings. The peptides bind specific HLA types, so they would only be effective in patients with matching immune profiles. Additionally, tumor heterogeneity means not all cervical cancers will carry PCLO mutations."},{"rthcId":"RPEP-14427","title":"Self-Assembly Peptide Hydrogel and its Application in the Biomedical Field.","authors":"Yuan, Libo; Zhang, Yu; Shuai, Yulu","year":2025,"journal":"Current drug delivery","doi":"10.2174/0115672018363733250227071908","pmid":"40370234","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14428","title":"Sleep and circadian effects on the incretin system.","authors":"Yuan, Robin K; Zitting, Kirsi-Marja","year":2025,"journal":"Current sleep medicine reports, 11","doi":"10.1007/s40675-025-00337-9","pmid":"40933800","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14429","title":"Exploring the Antimicrobial Potential of LL-37 Derivatives: Recent Developments and Challenges.","authors":"Yuan, Yihao; Li, Jiapeng; Wei, Guotao; Shen, Ziyi; Li, Bo; Wu, Jiawei; Liu, Jing","year":2025,"journal":"ACS biomaterials science & engineering, 11(6), 3145-3164","doi":"10.1021/acsbiomaterials.4c02029","pmid":"40423576","tags":["LL-37","antimicrobial-peptides","cathelicidins"],"studyType":"review","evidenceStrength":"review","keyFinding":"This comprehensive review examines how scientists have modified LL-37 — the only human cathelicidin antimicrobial peptide — to overcome its key limitations: high production costs, reduced effectiveness under real physiological conditions, vulnerability to enzymatic breakdown, and toxicity to human cells.\n\nMultiple modification strategies have improved LL-37's clinical potential, including truncation (shortening the peptide while keeping its active region), amino acid substitutions, cyclization, and conjugation with nanocarrier delivery systems. Modified LL-37 derivatives show enhanced activity against bacterial biofilms and cell membranes, and some demonstrate synergy with traditional antibiotics.","whyItMatters":"Antibiotic resistance is one of the biggest threats to modern medicine, and antimicrobial peptides like LL-37 represent a fundamentally different approach to fighting infections. Unlike conventional antibiotics that target specific bacterial processes, LL-37 physically disrupts bacterial membranes — making it harder for bacteria to develop resistance. This review maps the path from a promising natural peptide to potentially viable clinical treatments.","specificNumbers":"","methodology":"Narrative review of the scientific literature on LL-37 modification techniques, structure-activity relationships, mechanisms of action, nanocarrier delivery systems, and clinical application status.","limitations":"As a review article, this synthesizes existing research rather than generating new data. The clinical translation of most LL-37 derivatives is still in early stages, and many findings come from in vitro or animal studies."},{"rthcId":"RPEP-14430","title":"Vascular endothelial growth factor (VEGF) and endogenous calcium-capturing gelatin methacrylate hydrogels promote bone tissue regeneration.","authors":"Yuan, Zhengchao; Wang, Xinyi; Li, Peng; Shafiq, Muhammad; Shang, Panpan; Han, Lu; Feng, Hao; Xu, Yuan; El-Newehy, Mohamed; Abdulhameed, Meera Moydeen; Jiang, Lianyong; Mo, Xiumei; Ren, Yijiu","year":2025,"journal":"Biomaterials, 322, 123352","doi":"10.1016/j.biomaterials.2025.123352","pmid":"40306156","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14431","title":"Elucidation of the treatment mechanism of pulsed radiofrequency based on its antiinflammatory effects.","authors":"Yuba, Tomoo; Koyama, Yoshihisa; Uematsu, Hironobu; Takahashi, Ayako; Matsuda, Yoichi; Fujino, Yuji; Shimada, Shoichi","year":2025,"journal":"Scientific reports, 15(1), 33611","doi":"10.1038/s41598-025-19045-z","pmid":"41023026","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"PRF applied to the sciatic nerve significantly reduced knee pain, synovitis, and inflammatory cytokines in a mouse model. Tracer studies and western blotting showed PRF inhibited axonal transport in small dorsal root ganglion neurons, suppressing secretion of CGRP and substance P into the knee joint. Critically, administering CGRP and substance P agonists completely reversed PRF's analgesic and anti-inflammatory effects, proving these neuropeptides are the essential mediators of PRF's therapeutic action.","whyItMatters":"CGRP and substance P are major neuropeptides involved in pain and inflammation — CGRP is already the target of breakthrough migraine drugs. Understanding that PRF works specifically by suppressing these peptides could help optimize the treatment for different pain conditions and may reveal new therapeutic approaches targeting these neuropeptide pathways.","specificNumbers":"","methodology":"Researchers used a monoiodoacetic acid-induced knee pain model in mice. PRF was applied to the sciatic nerve and its effects were assessed through pain behavior testing, synovitis scoring, inflammatory cytokine measurements, tracer studies to evaluate axonal transport, and western blotting of dorsal root ganglion neurons. Reversal experiments with CGRP and substance P agonists confirmed the causal mechanism.","limitations":"This is a mouse study using a chemically induced pain model, which may not fully represent human chronic pain conditions. The monoiodoacetic acid model specifically mimics osteoarthritis-type pain, limiting generalizability to other chronic pain types. Specific sample sizes and statistical values were not detailed in the abstract. Translation to human PRF treatment parameters would require clinical validation."},{"rthcId":"RPEP-14432","title":"Development of a risk prediction model for gastrointestinal adverse events associated with semaglutide administration in patients with type 2 diabetes mellitus.","authors":"Yue, Deyong; Hua, Xuesheng; Zhu, Ling; Wang, Jun; Gu, Lihua; Yuan, Zhengxia; Jian, Wenle; Chen, Yirong; Meng, Guoliang","year":2025,"journal":"Frontiers in endocrinology, 16, 1684395","doi":"10.3389/fendo.2025.1684395","pmid":"41255528","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14433","title":"Pro-healing impact of liraglutide on skin wounds in normoglycemic mice.","authors":"Yue, Han; Zhang, Xiaoling; Zhao, Zhiyi; Gong, Song; Shao, Shiying","year":2025,"journal":"International immunopharmacology, 147, 114050","doi":"10.1016/j.intimp.2025.114050","pmid":"39798474","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14434","title":"Identification, Molecular Docking Mechanism and Cellular Activity of Selenium-Enriched ACE Inhibitory Peptides from Oysters.","authors":"Yue, Zhuangzhuang; Xia, Zhen; Xu, Fei; Chen, Bingbing; Jiao, Shufei; Liang, Xingtang; Yin, Yanzhen; Miao, Jianyin","year":2025,"journal":"Molecules (Basel, Switzerland), 30(24)","doi":"10.3390/molecules30244818","pmid":"41471840","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The purified oyster fraction M4-2 had an ACE inhibitory IC50 of 0.774 mg/mL, 3.6 times more potent than the crude hydrolysate (IC50: 2.801 mg/mL). Ninety-one selenium-containing peptide sequences were identified by LC-MS/MS.\n\nThe two selected peptides showed strong ACE binding: SeMFRTSSK (-9.8 kcal/mol, binding via hydrogen bonds to active pocket residues) and QASeMNEATGGK (-9.0 kcal/mol, interacting with the Zn²⁺ active center). At 0.025 mg/mL in EA.hy926 endothelial cells, SeMFRTSSK and QASeMNEATGGK enhanced NO release by 202.65% and 273.45% respectively, while suppressing ET-1 secretion by 18.03% and 27.86% — outperforming captopril on both measures. Both peptides were non-cytotoxic up to 0.25 mg/mL.","whyItMatters":"Hypertension affects over a billion people worldwide and is the leading modifiable risk factor for heart disease and stroke. ACE inhibitor drugs are effective but cause side effects like persistent cough and angioedema. Finding natural ACE-inhibitory peptides from food sources could offer a gentler alternative or complement for blood pressure management. The selenium enrichment adds another dimension — selenium is an essential trace element with antioxidant properties, making these peptides potentially dual-functional.","specificNumbers":"","methodology":"Selenium-enriched oyster proteins were digested with trypsin and purified through ultrafiltration and two-step reversed-phase HPLC to isolate the most ACE-inhibitory fraction. LC-MS/MS identified 91 selenium-containing peptide sequences. Molecular docking simulations predicted binding interactions with the ACE enzyme. The two most promising peptides were tested in EA.hy926 endothelial cells for cytotoxicity, nitric oxide release, and endothelin-1 secretion, with captopril as the positive control.","limitations":"This is an in vitro study using endothelial cell cultures — the peptides have not been tested in animals or humans for actual blood pressure reduction. Oral bioavailability is unknown — the peptides may be degraded during digestion before reaching the bloodstream. The comparison to captopril was in cell culture, not at equivalent systemic doses, so the claim of superiority may not translate in vivo. The selenium content and its specific contribution to bioactivity versus the peptide backbone are not separated. The oyster source requires selenium-enriched cultivation conditions."},{"rthcId":"RPEP-14435","title":"GLP-1R signaling does not modify the severity of experimental graft versus host disease.","authors":"Yusta, Bernardo; Wong, Chi Kin; Matthews, Dianne; Koehler, Jacqueline A; Baggio, Laurie L; Bang, Kw Annie; Drucker, Daniel J","year":2025,"journal":"Molecular metabolism, 100, 102235","doi":"10.1016/j.molmet.2025.102235","pmid":"40846075","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14436","title":"Impact of licorice supplementation on cardiac biomarkers and histomorphological changes in rats.","authors":"Yuzhu, Liu; Othman, Rosfayati; Md Salleh, Muhd Fakh Rur Razi; Arumugam, Sudha; Keah, Lee Siew; Chin, Jin Han","year":2025,"journal":"Journal of complementary & integrative medicine, 22(4), 661-668","doi":"10.1515/jcim-2025-0027","pmid":"40967600","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14437","title":"A membrane perspective on peptide-membrane interactions: recent results from solid-state NMR.","authors":"Zaatouf, Laila; Legras-Hemonnot, Hugo; Warschawski, Dror E","year":2025,"journal":"Biomedical journal, 100943","doi":"10.1016/j.bj.2025.100943","pmid":"41371586","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14438","title":"Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis: A Narrative Review.","authors":"Zacharia, George S; Gongati, Sudharsan R; Kharel, Aayush; Jacob, Anu","year":2025,"journal":"Cureus, 17(10), e95632","doi":"10.7759/cureus.95632","pmid":"41322896","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide has demonstrated efficacy in treating metabolic dysfunction-associated steatohepatitis (MASH), resolving steatohepatitis and improving hepatic fibrosis. It has been approved alongside resmetirom for treating non-cirrhotic MASH with moderate-to-advanced fibrosis. The review traces semaglutide's development from the discovery of GLP-1's role in glucose homeostasis through to its expanding clinical applications, which now include glycemic control, weight reduction, cardiovascular risk reduction, and liver disease treatment.","whyItMatters":"MASH (formerly NASH) is the most common liver disease worldwide and a leading cause of liver transplantation. Until recently, there were no approved drug treatments. Semaglutide's approval for MASH represents a major expansion of GLP-1 peptide therapeutics into liver disease, demonstrating that this peptide drug class has effects far beyond diabetes and obesity management.","specificNumbers":"Review covers GLP-1 RA development: exenatide → liraglutide → dulaglutide → semaglutide → tirzepatide · semaglutide approved for MASH with moderate-to-advanced fibrosis · weekly subcutaneous or oral formulation","methodology":"This is a narrative review covering the pharmacology of GLP-1 and semaglutide, its mechanism of action, clinical trial evidence for MASH treatment, safety profile, and comparison with other MASH therapeutic approaches.","limitations":"As a narrative review, it does not systematically evaluate all available evidence. Semaglutide's approval for MASH is relatively recent, so long-term outcomes and optimal treatment duration are not yet established. The review does not quantify the magnitude of fibrosis improvement or steatohepatitis resolution rates in detail. Head-to-head comparisons with resmetirom are limited."},{"rthcId":"RPEP-14439","title":"Review Article: GLP-1 Receptor Agonists and Glucagon/GIP/GLP-1 Receptor Dual or Triple Agonists-Mechanism of Action and Emerging Therapeutic Landscape in MASLD.","authors":"Zafer, Maryam; Tavaglione, Federica; Romero-Gómez, Manuel; Loomba, Rohit","year":2025,"journal":"Alimentary pharmacology & therapeutics, 61(12), 1872-1888","doi":"10.1111/apt.70196","pmid":"40364529","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14440","title":"Impact of Glucagon-Like Peptide-1 Receptor Agonists on Hip Arthroplasty Outcomes: A Systematic Review and Meta-Analysis.","authors":"Zaffar, Haroon; Imran, Mohammed A; Hussain, Sulaiman; Rushd, Farwah","year":2025,"journal":"Cureus, 17(11), e96279","doi":"10.7759/cureus.96279","pmid":"41362522","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14441","title":"Photoinduced electron transfer enhances the tumor-targeted photodynamic activity of bombesin metallopeptides incorporating an Ir(III) complex and carboxyfluorescein.","authors":"Zafon, Elisenda; Riesco-Llach, Gerard; Echevarría, Igor; Martínez-Alonso, Marta; Planas, Marta; Feliu, Lidia; Espino, Gustavo; Massaguer, Anna","year":2025,"journal":"Bioorganic chemistry, 166, 109142","doi":"10.1016/j.bioorg.2025.109142","pmid":"41167061","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14442","title":"The blueprint of neurocardiac crosstalk in arrhythmic syndromes.","authors":"Zaglia, Tania; Perumal Vanaja, Induja; Guazzo, Anna; Mongillo, Marco","year":2025,"journal":"American journal of physiology. Cell physiology, 329(4), C1038-C1045","doi":"10.1152/ajpcell.00558.2025","pmid":"40857213","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review establishes that sympathetic activation is both an acute arrhythmic trigger and a chronic driver of disease progression in inherited arrhythmogenic syndromes. Neuropeptide Y (NPY) and regional cardiac innervation patterns play critical roles in shaping myocardial excitability, tissue remodeling, and arrhythmogenesis.\n\nIn CPVT, arrhythmias are triggered by sympathetic stimulation in structurally normal hearts through calcium-handling abnormalities. In ACM, maladaptive autonomic remodeling including neurogenic fibrofatty infiltration creates an amplified arrhythmic substrate. The authors propose NPY antagonism as an emerging peptidergic therapy alongside β-blockade and left cardiac sympathetic denervation.","whyItMatters":"Sudden cardiac death from inherited arrhythmias is a devastating outcome, particularly in young people. Current treatments (beta-blockers, defibrillators, nerve surgery) are incomplete. Identifying NPY as a treatable mechanism opens a new peptide-based therapeutic avenue that could improve survival in patients with these genetic heart conditions.","specificNumbers":"","methodology":"This is a narrative review synthesizing current evidence on neurocardiac crosstalk in inherited arrhythmogenic syndromes. The authors analyze CPVT and ACM as representative conditions on a functional-structural continuum, examining the roles of β-adrenergic signaling, neuropeptide Y, and autonomic innervation patterns in disease mechanisms.","limitations":"This is a narrative review presenting a conceptual framework rather than new experimental data. NPY antagonism as therapy is described as emerging, with limited clinical evidence currently available. The framework is primarily based on CPVT and ACM; applicability to other arrhythmic syndromes needs validation. The relative contribution of NPY versus other sympathetic mediators is not fully quantified."},{"rthcId":"RPEP-14443","title":"A single injection of neuropeptide QRFP in the lateral hypothalamus decreased food intake.","authors":"Zagorácz, Olga; Ollmann, Tamás; Péczely, László; László, Kristóf; Kovács, Anita; Berta, Beáta; Kállai, Veronika; Kertes, Erika; Vörös, Dávid; Dusa, Daniella; Szábó, Ádám; Lénárd, László","year":2025,"journal":"Journal of psychopharmacology (Oxford, England), 39(3), 254-264","doi":"10.1177/02698811241311454","pmid":"39921588","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14444","title":"Oral Collagen Oligopeptides as a Modulator of Skin Health: A Comprehensive Evaluation of Clinical and Molecular Effects.","authors":"Zague, Vivian; Pinheiro, Ana Lucia Tabarini Alves; Pinto, Juliana Rodrigues; Facchini, Gustavo; Eberlin, Samara","year":2025,"journal":"Journal of medicinal food, 28(9), 869-876","doi":"10.1089/jmf.2024.0252","pmid":"40518844","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Clinical trial results (85 women, 84 days):\n- Skin firmness: significantly improved vs placebo (P < 0.05)\n- Skin elasticity: significantly improved vs placebo (P < 0.05)\n- Skin hydration: improved but did not reach statistical significance\n\nPreclinical molecular findings (human dermal fibroblasts):\n- Type I procollagen gene expression: significantly increased\n- Decorin and biglycan: significantly increased (these organize collagen architecture)\n- Versican: decreased (shifts toward tighter collagen organization)\n- MMP-1: decreased (less collagen breakdown) with increased TIMP-1 (more collagen protection)\n- Hyaluronic acid: effects measured alongside other ECM components\n\nThe combination shows Col-OP promotes collagen synthesis while inhibiting its degradation.","whyItMatters":"Collagen supplements are a billion-dollar industry, but much of the marketing has outpaced the science. This study addresses a key gap: not only does it demonstrate clinical efficacy in a rigorous placebo-controlled trial, but it also reveals the molecular mechanisms — collagen peptides don't just provide raw materials, they actually signal skin cells to produce more collagen, organize it better, and break it down less. This mechanistic understanding elevates collagen peptides from a supplement claim to a scientifically characterized intervention.","specificNumbers":"","methodology":"Two complementary approaches: (1) Double-blind, randomized, placebo-controlled clinical trial with 85 women aged 45-60 receiving 2.5 g Col-OP or placebo daily for 84 days. Skin hydration measured by Corneometer, firmness and elasticity by Cutometer. (2) Preclinical in vitro studies treating human dermal fibroblasts with Col-OP (1.0, 3.16, 10.0 mg/mL) for 96 hours, measuring gene expression and protein levels of type I collagen, MMP-1, TIMP-1, decorin, versican, biglycan, and hyaluronic acid by qPCR and ELISA.","limitations":"The clinical trial sample (85 women) is moderate but limited to women aged 45-60 — results may differ in other demographics. Skin hydration didn't reach significance despite a trend, suggesting the primary effects are structural (firmness/elasticity) rather than moisturizing. The in vitro fibroblast studies use higher peptide concentrations than would reach the dermis after oral supplementation, raising questions about dose translation. The 84-day trial may not capture long-term effects. No assessment of whether improvements persist after supplementation stops."},{"rthcId":"RPEP-14445","title":"Efficacy and Safety of Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists for Spinal Fusion Outcomes: A Comprehensive Meta-Analysis.","authors":"Zahed, Mohamed; Elmesalmi, Mahmoud; Al-Kharouf, Khaled F; Elbahnasawy, Sara E; El Menawy, Ziad; Elhanash, Salam; Odeh, Mahmoud; Elnaggar, Nour; Hesham Gamal, Mohamed; Elhady, Mahmoud M","year":2025,"journal":"Cureus, 17(9), e93065","doi":"10.7759/cureus.93065","pmid":"41141191","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14446","title":"Neurological complications associated with rapid weight loss and nutritional deficiencies following GLP-1 agonist use: a case report.","authors":"Zahir, Ali; Collins, David; Ip, Seyvonne; Samghabadi, Peyman; Douglas, Vanja C; LaHue, Sara C","year":2025,"journal":"BMC neurology, 26(1), 5","doi":"10.1186/s12883-025-04540-7","pmid":"41299410","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14447","title":"Beyond Weight Loss: Optimizing GLP-1 Receptor Agonist Use in Children.","authors":"Zaitoon, Hussein; Wauters, Aimee D; Rodriguez, Luisa M; Lynch, Jane L","year":2025,"journal":"Children (Basel, Switzerland), 12(11)","doi":"10.3390/children12111427","pmid":"41300545","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Liraglutide and semaglutide consistently produced clinically meaningful reductions in BMI, body weight, and waist circumference in adolescents with obesity, with modest improvements in systolic blood pressure and minimal effects on lipid levels or HbA1c. Newer trials have begun evaluating GLP-1RAs in children aged 6 and older.\n\nCritical knowledge gaps include pediatric pharmacokinetics, optimal dosing strategies, long-term developmental safety (particularly musculoskeletal health), nutritional adequacy during rapid weight loss in growing children, and the risk of misuse. The review concludes that pediatric-specific protocols are essential to safely translate adult GLP-1 agonist success to younger populations.","whyItMatters":"Childhood obesity affects over 340 million children worldwide and is a major driver of early-onset type 2 diabetes, heart disease, and psychological harm. While GLP-1 drugs show clear efficacy, children are not small adults — their growing bodies have different nutritional needs, and rapid weight loss during development could have consequences not seen in adult trials. Getting this right is critical as prescriptions for children surge.","specificNumbers":"","methodology":"Structured review of randomized controlled trials, extension studies, and mechanistic investigations evaluating GLP-1 receptor agonists in pediatric obesity and type 2 diabetes. Outcomes assessed included body weight, BMI, body composition, glycemic control, and adverse events.","limitations":"This is a structured review, not a systematic review or meta-analysis. Most RCT data comes from adolescents (12+), with very limited data in younger children. Long-term follow-up beyond 1-2 years is largely unavailable. Effects on musculoskeletal development, puberty, and final adult height are unknown. The review acknowledges significant gaps in pediatric pharmacokinetics and optimal dosing."},{"rthcId":"RPEP-14448","title":"Glucagon-Like Peptide-1 Receptor Agonists Combined With Personalized Digital Health Care for the Treatment of Metabolic Syndrome in Adults With Obesity: Retrospective Observational Study.","authors":"Zakaria, Hala; Jabri, Hadoun; Alshehhi, Sheikha; Caccelli, Milena; Debs, Joelle; Said, Yousef; Kattan, Joudy; Almarzooqi, Noah; Hashemi, Ali; Almarzooqi, Ihsan","year":2025,"journal":"Interactive journal of medical research, 14, e63079","doi":"10.2196/63079","pmid":"40146920","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Over 6 months, tirzepatide reduced waist circumference by 18.08 cm vs. 13.04 cm with semaglutide (p<0.001). Both drugs significantly lowered triglycerides (tirzepatide: -64.42 mg/dL, semaglutide: -70.70 mg/dL, both p<0.001). Tirzepatide showed greater improvements in fasting glucose, blood pressure, LDL, and total cholesterol. The highest digital engagement group (≥25 interactions) showed dramatically better outcomes: waist circumference -19.04 cm vs. -9.60 cm (p=0.002), triglycerides -108.56 vs. -44.49 mg/dL (p=0.02), diastolic BP -10.33 vs. -0.83 mmHg (p=0.004), and fasting glucose -18.60 vs. -2.49 mg/dL (p=0.02). The highest engagement quartile had 60% greater likelihood of metabolic syndrome reversal.","whyItMatters":"GLP-1 drugs are transforming obesity and metabolic disease treatment, but medication alone doesn't maximize outcomes. This study provides early evidence that combining these powerful peptide drugs with digital health coaching — making the intervention a comprehensive lifestyle + medication program — produces superior results. The clear dose-response relationship between app engagement and outcomes suggests that the behavioral component isn't just nice-to-have; it's a significant driver of results.","specificNumbers":"","methodology":"Retrospective observational study of 51 participants (mean age 45, mean BMI 35) in the Zone.Health weight loss program over 6 months. Participants were treated with either tirzepatide or semaglutide and received continuous support via a digital health platform with real-time monitoring and personalized feedback from an integrated care team. Engagement was measured by frequency of inbound app interactions and categorized into three groups.","limitations":"This is a small retrospective observational study (n=51) without a control group, so it's impossible to separate the effects of medication from digital coaching. The engagement-outcome correlation could reflect motivation bias — more motivated patients may both engage more and achieve better results regardless of the platform. Only 6 months of follow-up was reported. The study was conducted through a commercial weight loss program (Zone.Health), which may introduce selection bias."},{"rthcId":"RPEP-14449","title":"The efficacy and safety of glucagon-like peptide-1 receptor agonists in non-diabetic adults with overweight/obesity: An umbrella review of systematic reviews and meta-analyses.","authors":"Zamanian, Nazanin; Imani, Hossein; Talebi, Sepide; Rahimlou, Mehran; Khosroshahi, Reza Amiri; Mohammadi, Hamed","year":2025,"journal":"European journal of pharmacology, 1003, 177966","doi":"10.1016/j.ejphar.2025.177966","pmid":"40680981","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14450","title":"Semaglutide Overdose in a Diabetic Patient: Suicidal Behavior and Multiorgan Failure.","authors":"Zamir, Doron; Ovadia, Yaniv S; Ben-Bassat, Ofer; Zamir, Mariana; Malnick, Stephen D H","year":2025,"journal":"The American journal of case reports, 26, e947682","doi":"10.12659/AJCR.947682","pmid":"40849680","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A patient on weekly 1 mg semaglutide for one year self-injected his entire monthly prescription at once (approximately 4 times the recommended dose) during a period of dysphoria. He presented 14 days later with multiorgan failure, hypoglycemia, cholestatic liver dysfunction, two duodenal ulcers, and a two-week history of weakness, appetite loss, epigastric pain, severe diarrhea, melena, and syncope.\n\nThe authors characterize this as possible suicide-related behavior based on six criteria: the patient's prior treatment experience, ability to self-inject, awareness that a single injection is limited to the weekly dose, the intentional injection of multiple doses exceeding the monthly supply, the safety of the pen delivery system, and self-reported dysphoria before the event. The patient's clinical status improved gradually, including ulcer healing by discharge.","whyItMatters":"As semaglutide prescriptions surge worldwide for both diabetes and weight loss, understanding potential psychiatric side effects and overdose consequences becomes increasingly important. This case highlights two concerns: the potential link between GLP-1 drugs and mood changes that could lead to self-harm, and the serious medical consequences of semaglutide overdose — a scenario that may become more common as these drugs become more widely available.","specificNumbers":"","methodology":"This is a single-patient case report describing the clinical presentation, diagnostic workup, treatment course, and outcome of a semaglutide overdose. The authors retrospectively assessed the circumstances of the overdose, including the patient's mental state, and conducted a clinical review of the link between GLP-1 receptor agonists and suicidal behavior.","limitations":"This is a single case report, which is the weakest form of clinical evidence and cannot establish causation between semaglutide and suicidal behavior. The patient's mood state before the overdose was assessed retrospectively and may be subject to recall bias. Pre-existing psychiatric conditions are not fully characterized. Whether the multiorgan failure was entirely caused by the semaglutide overdose or involved other factors is uncertain. One case cannot distinguish between drug-induced mood changes and coincidental depression."},{"rthcId":"RPEP-14451","title":"Dual-Site Targeting by Peptide Inhibitors of the N-Terminal Domain of Hsp90: Mechanism and Design.","authors":"Zang, Min; Gan, Haipeng; Zhou, Xuejie; Wang, Lei; Dong, Hao","year":2025,"journal":"Journal of chemical information and modeling, 65(10), 5113-5123","doi":"10.1021/acs.jcim.5c00629","pmid":"40310892","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14452","title":"Potential application of Healitide-GP1, a novel antibacterial peptide, in wound healing: in vitro studies.","authors":"Zare-Zardini, Hadi; Seyedjavadi, Sima Sadat","year":2025,"journal":"Scientific reports, 15(1), 31078","doi":"10.1038/s41598-025-17002-4","pmid":"40849541","tags":["antimicrobial-peptides"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Researchers used machine learning and a genetic algorithm to design a brand-new antibacterial peptide called Healitide-GP1, then validated it in lab experiments. The peptide proved safe for human skin cells at concentrations above 200 µg/mL in both dermal fibroblasts (HDF) and keratinocytes (HaCaT).\n\nIn wound-closure assays, Healitide-GP1 improved wound closure by 48% in fibroblasts and 52% in keratinocytes after just 24 hours. It also showed strong antibacterial activity against two common wound pathogens: Staphylococcus aureus (MIC: 12.5 µg/mL) and Escherichia coli (MIC: 25 µg/mL).\n\nBioinformatics analysis revealed that Healitide-GP1 has a unique hydrophobic motif and distinct evolutionary positioning compared to known antimicrobial peptides, suggesting it may work through a novel mechanism of action.","whyItMatters":"Infected wounds are a major clinical problem, especially with rising antibiotic resistance. A peptide that can simultaneously kill bacteria and accelerate wound healing addresses both problems at once — something conventional antibiotics cannot do. The AI-driven design approach is also significant: rather than screening natural peptides one by one, the researchers used machine learning to identify what makes wound-healing peptides effective, then used algorithms to generate entirely new sequences.","specificNumbers":"Cytocompatibility >200 µg/mL (HDF & HaCaT) · 48% wound closure in fibroblasts at 24h · 52% wound closure in keratinocytes at 24h · MIC 12.5 µg/mL vs S. aureus · MIC 25 µg/mL vs E. coli","methodology":"The researchers used a machine learning model to identify key features of wound-healing peptides (WHPs), then applied a genetic algorithm to generate novel peptide sequences. The top candidate, Healitide-GP1, was chemically synthesized and tested in the lab. Safety was assessed by measuring cell viability in human dermal fibroblasts and keratinocytes at increasing peptide concentrations. Wound-healing activity was measured using scratch assays (artificial wounds in cell monolayers). Antibacterial activity was determined by minimum inhibitory concentration (MIC) testing against S. aureus and E. coli.","limitations":"This is an in vitro study only — all experiments were done in cell cultures, not in living animals or humans. The wound-closure assay uses artificial scratches in cell monolayers, which is a simplified model of actual wound healing. Real wounds involve immune cells, blood flow, extracellular matrix, and infection dynamics that cell-culture models cannot replicate. No animal wound models or toxicity studies were performed. The peptide's stability in wound fluid and its behavior in vivo are unknown."},{"rthcId":"RPEP-14453","title":"The expanding role of semaglutide: beyond glycemic control.","authors":"Zarei, Malek; Sabetkasaei, Masoumeh; Mozafari, Masoud; Zaeri, Sasan","year":2025,"journal":"Journal of diabetes and metabolic disorders, 24(2), 160","doi":"10.1007/s40200-025-01663-z","pmid":"40620322","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14454","title":"Alcohol-based solvents as mobile phases for LC-MS characterization of therapeutic proteins.","authors":"Zarei, Mostafa; Jonveaux, Jérôme; Jahn, Michael","year":2025,"journal":"Journal of pharmaceutical and biomedical analysis, 262, 116879","doi":"10.1016/j.jpba.2025.116879","pmid":"40220636","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14455","title":"Diabetes-Kidney-Heart Continuum and Its Implication on Therapeutic Management.","authors":"Zargar, Abdul Hamid; Balagopalan, Jayagopal Pathiyil; Bhattacharyya, Arpandev; Almeida, Alan; Taraphder, Abhijit; Bansal, Sandeep; Dani, Sameer; Deka, Nilakshi; Jain, Sanjay; Swami, Onkar C","year":2025,"journal":"Cureus, 17(7), e88561","doi":"10.7759/cureus.88561","pmid":"40861717","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review outlines a framework for understanding and managing the diabetes-kidney-heart continuum through three stages:\n\n1. **Prevent**: Early risk stratification and intervention before vascular damage occurs\n2. **Regress**: Reversing early vascular changes when detected\n3. **Retard**: Slowing progression of established cardiovascular and kidney disease\n\nKey therapeutic classes for managing this continuum include SGLT2 inhibitors, GLP-1 receptor agonists, DPP-4 inhibitors, lipid-lowering therapy, and RAAS blockers — all with evidence for both cardiac and renal protection. New diagnostic biomarkers (BNP, NT-proBNP, cardiac troponin, cystatin C) and technologies (single-cell transcriptome sequencing) can detect vascular complications earlier than traditional methods.","whyItMatters":"Heart disease and kidney disease are the leading causes of death in people with type 2 diabetes, and they often develop together. Treating them as separate conditions misses the interconnected nature of the damage. This continuum framework helps clinicians think about diabetes complications holistically and choose therapies — like GLP-1 receptor agonists and SGLT2 inhibitors — that protect multiple organs at once, rather than treating each complication in isolation.","specificNumbers":"","methodology":"This is a narrative review synthesizing evidence on the pathophysiology, diagnosis, and management of vascular complications in type 2 diabetes, organized around the concept of a diabetes-kidney-heart continuum. The authors reviewed pharmacotherapy evidence for each drug class and summarized emerging diagnostic approaches.","limitations":"This is a narrative review, which may be subject to selection bias in the literature chosen. It does not present new primary data or conduct systematic analysis with predefined inclusion criteria. The three-stage framework (prevent, regress, retard) is conceptual and may oversimplify the complex, non-linear progression of diabetic complications. The review does not address cost-effectiveness or access barriers for the therapies discussed."},{"rthcId":"RPEP-14456","title":"Outcomes in Heart Failure With Improved Ejection Fraction Following Implantable Cardioverter-Defibrillator Placement for Primary Prevention.","authors":"Zarrella, Michael N; Borz-Baba, Carolina; Wakefield, Dorothy; Wynne, Kolu; Kett, Kevin","year":2025,"journal":"Cureus, 17(6), e85360","doi":"10.7759/cureus.85360","pmid":"40621223","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14457","title":"Controlled release of antimicrobial peptides from nanocellulose wound dressings for treatment of wound infections.","authors":"Zattarin, Elisa; Sotra, Zeljana; Wiman, Emanuel; Bas, Yagmur; Rakar, Jonathan; Berglund, Linn; Starkenberg, Annika; Björk, Emma M; Khalaf, Hazem; Oksman, Kristiina; Bengtsson, Torbjörn; Junker, Johan P E; Aili, Daniel","year":2025,"journal":"Materials today. Bio, 32, 101756","doi":"10.1016/j.mtbio.2025.101756","pmid":"40290891","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In a porcine (pig) wound infection model, the antimicrobial peptide PLNC8 αβ eradicated wound infections and promoted re-epithelialization (new skin growth over the wound).\n\nTwo types of nanocellulose dressings were tested: bacterial cellulose (BC) and wood-derived TEMPO-oxidized nanocellulose (TC). Both showed effective contact killing of bacteria on the dressing surface but were less effective against bacteria floating in wound fluid.\n\nThe breakthrough came from incorporating mesoporous silica nanoparticles (MSNs) into the dressings as peptide carriers. MSN-functionalized dressings achieved significantly higher peptide loading and sustained release, resulting in improved antimicrobial efficacy against both surface and suspended bacteria. All formulations showed low cytotoxicity toward human fibroblasts and keratinocytes.","whyItMatters":"Antibiotic-resistant wound infections are a growing crisis — chronic non-healing wounds affect millions of patients and cost healthcare systems billions annually. Antimicrobial peptides are promising alternatives to antibiotics because bacteria have difficulty developing resistance to them. By embedding a protease-resistant peptide in a wound dressing that slowly releases it, this approach could provide sustained infection control without repeated applications, directly addressing one of the biggest challenges in wound care.","specificNumbers":"","methodology":"Researchers developed two types of nanocellulose wound dressings (bacterial cellulose and TEMPO-oxidized wood nanocellulose) loaded with the antimicrobial peptide PLNC8 αβ. The peptide was either adsorbed directly onto nanocellulose fibers or encapsulated in mesoporous silica nanoparticles (MSNs) embedded in the dressings. They tested antimicrobial activity against bacteria, cytotoxicity against human primary fibroblasts and keratinocytes, and efficacy in a porcine (pig) wound infection model measuring both bacterial clearance and wound healing (re-epithelialization).","limitations":"While the pig wound model is more clinically relevant than mouse models, the study has not been tested in human patients. Specific quantitative data (exact bacterial counts, peptide release rates, healing times) are not provided in the abstract. The study used a single bacterial species or limited range of pathogens — real wound infections often involve mixed bacterial communities. Long-term stability and shelf-life of the functionalized dressings were not addressed."},{"rthcId":"RPEP-14458","title":"An Insight into Pharmaceutical Design and Pharmacokinetic Characteristics of GLP-1 RAs.","authors":"Zayed, Mohamed F; Khyat, Nada O; Alsibyani, Rawan W; Alshami, Rahaf Z; Alsubahi, Ramzyah A; Alamoudi, Mariam K","year":2025,"journal":"Current pharmaceutical design","doi":"10.2174/0113816128375766250720234005","pmid":"40798976","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14459","title":"Obesity-Related Glomerulosclerosis-How Adiposity Damages the Kidneys.","authors":"Zbrzeźniak-Suszczewicz, Justyna; Winiarska, Agata; Perkowska-Ptasińska, Agnieszka; Stompór, Tomasz","year":2025,"journal":"International journal of molecular sciences, 26(13)","doi":"10.3390/ijms26136247","pmid":"40650024","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14460","title":"Interactions of Galleria mellonella Proline-Rich Antimicrobial Peptides with Gram-Negative and Gram-Positive Bacteria.","authors":"Zdybicka-Barabas, Agnieszka; Stączek, Sylwia; Mak, Paweł; Kapral-Piotrowska, Justyna; Skrzypiec, Krzysztof; Wydrych, Jerzy; Pawlikowska-Pawlęga, Bożena; Gruszecki, Wiesław I; Cytryńska, Małgorzata","year":2025,"journal":"International journal of molecular sciences, 26(17)","doi":"10.3390/ijms26178438","pmid":"40943360","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Both proline-rich antimicrobial peptides (P1 and P2) from Galleria mellonella hemolymph demonstrated antibacterial activity against Gram-negative E. coli and Gram-positive M. luteus. The P2 peptide was approximately three times more effective than P1 in both reducing M. luteus survival and permeabilizing E. coli membranes.\n\nMicroscopy imaging revealed that both peptides caused significant changes in bacterial cell morphology, surface topography, and nanomechanical properties. The peptides also affected protein and lipid composition on cell surfaces differently depending on the bacterial type, highlighting distinct mechanisms of interaction with Gram-negative vs. Gram-positive bacteria.","whyItMatters":"With antibiotic resistance becoming a growing global health crisis, antimicrobial peptides from natural sources like insects represent a promising alternative. Understanding how these peptides attack bacteria at the molecular level could help scientists design new antimicrobial therapies.","specificNumbers":"","methodology":"Researchers purified two proline-rich peptides from wax moth hemolymph and tested them in lab experiments against E. coli and M. luteus bacteria. They used fluorescence microscopy to visualize peptide binding, atomic force microscopy and scanning electron microscopy to examine cell surface changes, and FTIR spectroscopy to analyze molecular-level interactions with bacterial membranes.","limitations":"This was entirely an in vitro (lab-based) study, so it's unclear whether these peptides would work the same way in a living organism. Only two bacterial species were tested, and the study did not evaluate toxicity to mammalian cells, which would be essential for any therapeutic application. The peptides were tested in isolation, not in combination with existing antibiotics."},{"rthcId":"RPEP-14461","title":"Prescription of Monoclonal Antibodies Against Calcitonin Gene-Related Peptide for the Prophylaxis of Migraine in Austria: A Retrospective, Longitudinal Analysis of Nationwide Insurance Data.","authors":"Zebenholzer, Karin; Gleiss, Andreas; Reichardt, Berthold; Gall, Walter; Wöber, Christian","year":2025,"journal":"European journal of neurology, 32(12), e70440","doi":"10.1111/ene.70440","pmid":"41342133","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14462","title":"Lacosamide versus topiramate in episodic migraine: a randomized controlled double-blinded trial.","authors":"Zeinhom, Mohamed G; Khalil, Mohamed Fouad Elsayed; Almoataz, Mohamed; Youssif, Tarek Youssif Omar; Daabis, Ahmed Mohamed Ali; Refat, Hossam Mohamed; Ebied, Ahmed Ahmed Mohamed Kamal; Georgy, Shady S; Akl, Ahmed Zaki Omar; Ismaiel, Mohamed; Ahmed, Salah Ibrahim; Eissa, Hesham Farouk; Ibrahem, Asmaa Ibrahem Desouky Mostafa; Hassan, Asmaa Mohammed; Elshafei, Mohamed; Egila, Amir Ahmed Elsaeed; Ahmed, Sherihan Rezk","year":2025,"journal":"Therapeutic advances in neurological disorders, 18, 17562864251396529","doi":"10.1177/17562864251396529","pmid":"41384236","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14463","title":"Efficacy, Tolerability, and Safety of Glucagon-Like Peptide 1 Receptor Agonists (GLP1-RA) in Kidney Transplant Recipients With Diabetes.","authors":"Zelada, Henry; Campana, Mario; Kawai, Kosuke; Redden, David; Agarwal, Gaurav; Gutierrez, Orlando M; Kumar, Vineeta","year":2025,"journal":"Clinical transplantation, 39(4), e70144","doi":"10.1111/ctr.70144","pmid":"40230336","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14464","title":"Balancing oral sequential absorption barriers of semaglutide-loaded nanoparticles by optimization of surface glycocholic acid density.","authors":"Zeng, Han; Li, Yiyao; Liu, Boyuan; Chu, Chenxiao; Feng, Yupeng; Xiao, Peifu; Yuan, Haoyang; Deng, Xiaopeng; Zhang, Yu; Yin, Tian; He, Haibing; Gou, Jingxin; Tang, Xing","year":2025,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 388(Pt 1), 114316","doi":"10.1016/j.jconrel.2025.114316","pmid":"41083011","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14465","title":"Harnessing the apical sodium-dependent bile acid transporter for enhanced oral delivery of peptide drugs: mechanisms, strategies, and therapeutic potential.","authors":"Zeng, Han; Li, Yiyao; Deng, Xiaopeng; Xiao, Peifu; Liu, Boyuan; Zhang, Yu; Yin, Tian; He, Haibing; Gou, Jingxin; Tang, Xing","year":2025,"journal":"Expert opinion on drug delivery, 22(9), 1375-1393","doi":"10.1080/17425247.2025.2524005","pmid":"40548518","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14466","title":"Engineered GLP-1R-targeting nanoplatforms: multimodal therapeutics in human diseases.","authors":"Zeng, Juan; Tang, Xinxin; Qin, Dalian; Yu, Lu; Zhou, Xiaogang; Feng, Chi; Mi, Jianing; Pan, Hudan; Wu, Jianming; Huang, Bin; Wu, Anguo","year":2025,"journal":"Journal of nanobiotechnology, 23(1), 682","doi":"10.1186/s12951-025-03677-4","pmid":"41088364","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14467","title":"Thymosin beta 4 as an Alzheimer disease intervention target identified using human brain organoids.","authors":"Zeng, Peng-Ming; Sun, Xin-Yao; Li, Yang; Wu, Wen-di; Huang, Jing; Cao, Dong-Dong; Qian, Pin-Jue; Ju, Xiang-Chun; Luo, Zhen-Ge","year":2025,"journal":"Stem cell reports, 20(9), 102601","doi":"10.1016/j.stemcr.2025.102601","pmid":"40816274","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14468","title":"Neuropeptide Y neurons mediate opioid-induced itch by disinhibiting GRP-GRPR microcircuits in the spinal cord.","authors":"Zeng, Qian; Li, Yitong; Wu, Yifei; Wu, Jiawei; Xu, Kangtai; Chen, Yiming; Rao, Yunfei; Li, Nan; Luo, Yuhui; Jiang, Changyu; Wu, Chaoran; Wang, Zilong","year":2025,"journal":"Nature communications, 16(1), 7074","doi":"10.1038/s41467-025-62382-w","pmid":"40750771","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14469","title":"ACE-inhibitory peptides from Morchella esculenta: screening, kinetics, and molecular dynamics simulation.","authors":"Zeng, Wenjun; Yu, Xudong; Chen, Mingfeng; Zhang, Huiling; Xu, Jucai; Zeng, Xiaofang; Liang, Ying","year":2025,"journal":"Food chemistry, 490, 145011","doi":"10.1016/j.foodchem.2025.145011","pmid":"40499431","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14470","title":"Universal peptide synthesis via solid-phase methods fused with chemputation.","authors":"Zero, Jacopo; Tyler, Tristan J; Cronin, Leroy","year":2025,"journal":"Nature communications, 16(1), 7322","doi":"10.1038/s41467-025-62344-2","pmid":"40781087","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14471","title":"Preclinical Evaluation of a Trop2-Targeted Peptide Probe for PET Imaging of Triple-Negative Breast Cancer.","authors":"Zha, Yuan; Zhu, Xue; Xue, Yan; Huang, Zhihong; Wang, Shuang; Jiao, Yang; Chen, Yu; Yao, Ying; Wang, Ke; Fang, Jing","year":2025,"journal":"Analytical chemistry, 97(42), 23598-23608","doi":"10.1021/acs.analchem.5c05242","pmid":"41105928","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14472","title":"Artificial intelligence in peptide-based drug design.","authors":"Zhai, Silong; Liu, Tiantao; Lin, Shaolong; Li, Dan; Liu, Huanxiang; Yao, Xiaojun; Hou, Tingjun","year":2025,"journal":"Drug discovery today, 30(2), 104300","doi":"10.1016/j.drudis.2025.104300","pmid":"39842504","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14473","title":"Semaglutide improves cognitive function and neuroinflammation in APP/PS1 transgenic mice by activating AMPK and inhibiting TLR4/NF-κB pathway.","authors":"Zhai, Yanyu; Lu, Kaili; Yuan, Yuan; Zhang, Ziyao; Xue, Lixia; Zhao, Fei; Xu, Xiaofeng; Wang, Hongmei","year":2025,"journal":"Journal of Alzheimer's disease : JAD, 105(2), 416-432","doi":"10.1177/13872877251329439","pmid":"40151913","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In APP/PS1 transgenic Alzheimer's mice treated with semaglutide for 8 weeks:\n\n- Cognitive function improved on Morris water maze testing\n- Amyloid-beta (Aβ) plaque accumulation was reduced\n- Microglial and astrocyte overactivation was inhibited\n- Inflammatory mediator secretion was decreased\n- AMP-activated protein kinase (AMPK) was robustly activated\n- TLR4/NF-κB inflammatory signaling cascade was suppressed\n\nTranscriptomic profiling (RNA sequencing) confirmed the anti-inflammatory mechanism at the gene expression level, providing multi-level evidence for semaglutide's neuroprotective effects.","whyItMatters":"Semaglutide (Ozempic/Wegovy) is already used by millions for diabetes and weight loss. If it can also protect against Alzheimer's disease — the most common form of dementia affecting 55 million people worldwide — the public health impact would be enormous. This study identifies a specific anti-inflammatory mechanism (AMPK activation → TLR4/NF-κB suppression) that explains how semaglutide might protect the brain. Multiple clinical trials are already underway testing semaglutide in Alzheimer's patients, and mechanistic studies like this inform those efforts.","specificNumbers":"","methodology":"Male APP/PS1 transgenic mice (a standard Alzheimer's model expressing mutant human amyloid precursor protein and presenilin-1) were treated with semaglutide or vehicle for 8 weeks. Cognitive function was assessed using the Morris water maze. Brain pathology was analyzed for amyloid plaque deposition. High-throughput RNA sequencing identified gene expression changes. Microglia and astrocyte activation were assessed by immunofluorescent staining. Inflammatory cytokines were measured by ELISA. AMPK and TLR4/NF-κB pathway proteins were evaluated by western blot.","limitations":"This is a preclinical study in transgenic mice that overexpress mutant human proteins, which may not fully recapitulate human Alzheimer's disease. Only male mice were used, missing potential sex differences. The 8-week treatment is short relative to the decades-long progression of human AD. The APP/PS1 model focuses on amyloid pathology and doesn't capture tau tangles, another hallmark of human Alzheimer's. Semaglutide dosing in mice may not translate directly to human dosing and brain exposure."},{"rthcId":"RPEP-14474","title":"CGRP-Loaded ROS-Responsive Hydrogel Restores Neuro-Angiogenic Signaling to Promote Bone Regeneration in Diabetes-Associated Periodontitis.","authors":"Zhan, Chaoning; Dai, Qingyi; Ren, Jianhan; Jin, Lijian; Wang, Weiping; Ye, Zhou; Tsoi, James Kit Hon; Lin, Yifan","year":2025,"journal":"Advanced science (Weinheim, Baden-Wurttemberg, Germany), 12(40), e06438","doi":"10.1002/advs.202506438","pmid":"40755317","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14475","title":"Pdia3 deficiency exacerbates intestinal injury by disrupting goblet and Paneth cell function during ischemia/reperfusion.","authors":"Zhan, Yaqing; Deng, Qiwen; Jia, Yifan; Chen, Zhaorong; Zhao, Xu; Ling, Yihong; Qiu, Yuxin; Wang, Xiwen; Wang, Fan; He, Muchen; Huang, Wenqi; Shen, Jiantong; Wen, Shihong","year":2025,"journal":"Cellular signalling, 130, 111682","doi":"10.1016/j.cellsig.2025.111682","pmid":"39988288","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"PDIA3 is highly expressed in healthy intestinal epithelial cells, particularly in goblet and Paneth cells. In patients with mesenteric artery ischemia, PDIA3 expression was reduced, correlating with disease severity.\n\nIn intestinal epithelium-specific Pdia3 knockout mice, ischemia/reperfusion injury was significantly more severe, with impaired goblet cell mucus production, reduced Paneth cell antimicrobial peptide secretion, and dysbiotic gut microbiota. Treatment with recombinant defensin α1 — an antimicrobial peptide normally secreted by Paneth cells — significantly alleviated the adverse effects of Pdia3 deficiency, restoring microbiota balance and reducing intestinal inflammation.","whyItMatters":"Intestinal ischemia/reperfusion injury has high mortality and limited treatment options. This study identifies PDIA3 as a critical upstream regulator of gut defense and shows that a recombinant antimicrobial peptide can compensate when this system fails — opening a potential new therapeutic approach using peptide-based treatments for acute intestinal injury.","specificNumbers":"","methodology":"The study combined human clinical data (mesenteric ischemia patients) with a mouse model using intestinal epithelium-specific conditional Pdia3 knockout mice subjected to intestinal ischemia/reperfusion. Techniques included single-cell RNA sequencing, immunohistochemistry, transcriptomic analysis, and statistical correlation (Pearson's) between PDIA3 expression and disease severity. The therapeutic rescue was tested with recombinant defensin α1 administration.","limitations":"The therapeutic rescue with defensin α1 was demonstrated only in mice, and the human data was correlational rather than interventional. The study focused on a specific injury model (ischemia/reperfusion), so findings may not generalize to all forms of intestinal damage. Specific dosing and timing of defensin α1 treatment were not detailed in the abstract."},{"rthcId":"RPEP-14476","title":"A microporous liraglutide-releasing silk fibroin scaffold improves islet transplantation outcomes through anti-inflammatory effect.","authors":"Zhan, Yixiang; Du, Xinchen; Li, Yan; Wang, Yingbo; Cai, Xiangheng; Yang, Runnan; Jiang, Tingsheng; Liu, Zhaoce; Yu, Xueer; Lin, Shanshan; Liu, Qing; Qi, Yingyi; Liang, Rui; Liu, Na; Liu, Tengli; Hu, Xiaoyan; Zou, Jiaqi; Ding, Xuejie; Sun, Peng; Feng, Houhan; Yang, Jiuxia; Wang, Lianyong; Wang, Shusen","year":2025,"journal":"Cell transplantation, 34, 9636897251374147","doi":"10.1177/09636897251374147","pmid":"40956865","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14477","title":"The Analysis of miRNA-mRNA Network Regulation Revealed the Mechanism of Different Drugs-Induced Constipation in Mice.","authors":"Zhan, Yu; Wen, Yong; Qu, Jing-Hui; Tang, Xue-Gui","year":2025,"journal":"Biochemical genetics","doi":"10.1007/s10528-025-11164-6","pmid":"40610816","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14478","title":"Tirzepatide reduces body weight by increasing fat utilization via the central nervous system-adipose tissue axis in male mice.","authors":"Zhang, Ailin; Liu, Qinhui; Xiong, Yimin; Li, Jiahui; Xu, Ying; Song, Haiying; Jing, Xiandan; Xu, Haixia; Yang, Na; Li, Yanping; Mo, Li; Tang, Qin; He, Jinhan","year":2025,"journal":"Diabetes, obesity & metabolism, 27(5), 2844-2856","doi":"10.1111/dom.16294","pmid":"40000395","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14479","title":"Effects of SGLT2 inhibitors and GLP-1 receptor agonists on glycemic variability, islet cell function, and insulin resistance in patients with type 2 diabetes mellitus and renal cell carcinoma.","authors":"Zhang, Anqi; Zhang, Xincheng; Yang, Aige; Dong, Shanshan; Wang, Lina; Zhou, Huimin; Hu, Xiaopeng","year":2025,"journal":"American journal of cancer research, 15(3), 946-965","doi":"10.62347/OLUR1927","pmid":"40226468","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14480","title":"Characterization of a Bovine Serum Albumin-Derived Pro-Cognitive Peptide (bSAPP): An Orally Active Peptide Alleviates Cognitive Decline in HFD-Fed Mice via CCK Signaling Through the Gut-Brain Axis.","authors":"Zhang, Biyun; Ando, Mone; Kawano, Kohei; Iwasaki, Yusaku; Inoue, Kazuo; Ohinata, Kousaku","year":2025,"journal":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 39(24), e71366","doi":"10.1096/fj.202503006R","pmid":"41405891","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14481","title":"Effect of Terminal Modifications on the Antimicrobial Activity of the Designed G3 Peptide.","authors":"Zhang, Bo; Xu, Xinyu; Zhou, Wei; Zhao, Xiubo","year":2025,"journal":"Langmuir : the ACS journal of surfaces and colloids, 41(43), 29229-29239","doi":"10.1021/acs.langmuir.5c03844","pmid":"41121613","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14482","title":"Integrating micro-needle jet injection and sustained GLP-1 therapy with structured feeding: a comprehensive strategy for obesity management.","authors":"Zhang, Chen; Long, Luoxin; Hu, Hong; Zhou, Xinjin; Mao, Lindsey F; Wang, Jing; Zhang, Aoran; Wang, Yuji; Yan, Yi; Mao, Shanhong","year":2025,"journal":"Drug delivery, 32(1), 2557938","doi":"10.1080/10717544.2025.2557938","pmid":"40926521","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14483","title":"Peptide-driven approaches in advanced wound healing materials.","authors":"Zhang, Chen; Meng, Lei; Sethi, Gautam; Wang, Jinxiang; Li, Baisen","year":2025,"journal":"Drug discovery today, 30(9), 104440","doi":"10.1016/j.drudis.2025.104440","pmid":"40749937","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14484","title":"DiWB-1: A Luteinizing Hormone Releasing Hormone (LHRH)-Targeted Peptide-Drug Conjugate (PDC) With Enhanced Tumor Selectivity and PI3K Inhibition Efficacy.","authors":"Zhang, Chenyu; Zhong, Honglan; Li, Xiang; Xing, Zhenjian; Li, Siming; Yu, Rui; Deng, Xin","year":2025,"journal":"Archiv der Pharmazie, 358(6), e70021","doi":"10.1002/ardp.70021","pmid":"40544488","tags":["peptide-drug-conjugate","lhrh","cancer"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"Researchers created DiWB-1, a peptide-drug conjugate that links an LHRH-receptor-targeting peptide to the PI3K inhibitor buparlisib. DiWB-1 was more potent than buparlisib alone against LHRH-receptor-positive breast cancer cells (IC50 of 1.8 μM vs 2.4 μM) while being less toxic to normal cells. In mice, DiWB-1 suppressed tumors effectively while avoiding the liver damage, kidney damage, and blood sugar spikes caused by buparlisib alone. The conjugate also showed favorable metabolic stability with a half-life of 5.6 hours, slightly longer than the established peptide drug triptorelin (4.2 hours).","whyItMatters":"PI3K inhibitors are effective against certain cancers but cause serious side effects because they hit healthy cells too. By attaching buparlisib to a peptide that homes in on LHRH receptors — which are overexpressed on many cancer types — the researchers created a drug that preferentially accumulates in tumors. This peptide-drug conjugate approach could make potent but toxic cancer drugs safer and more effective by delivering them directly to cancer cells.","specificNumbers":"IC50: 1.8 μM (DiWB-1) vs 2.4 μM (buparlisib alone) · Half-life: 5.6h (DiWB-1) vs 4.2h (triptorelin) · No liver/kidney damage · No hyperglycemia · Reduced toxicity in normal cells","methodology":"The researchers developed the LHRH-targeting peptide IV-6, characterized its receptor affinity and metabolic stability, then conjugated it to buparlisib to form DiWB-1. They tested anti-cancer activity in vitro against LHRH-receptor-positive MDA-MB-231 breast cancer cells and normal cells. In vivo efficacy was assessed in a mouse xenograft tumor model, with toxicity evaluated via organ histology and blood chemistry. Pharmacokinetic studies measured half-life and metabolic stability.","limitations":"This is preclinical research using a single cancer cell line (MDA-MB-231) and mouse xenograft models. The improvement in IC50 over buparlisib alone is modest (1.8 vs 2.4 μM). The study only tested LHRH-receptor-positive tumors; efficacy against receptor-negative cancers is unknown. Human pharmacokinetics and safety are not established. Manufacturing complexity and cost of the PDC are not discussed."},{"rthcId":"RPEP-14485","title":"Dual Conjugation of Long- and Medium-Chain Fatty Acids to BimBH3 Peptide Yields Ultra Long-Acting Inhibitors of Intracellular PTPN1/2.","authors":"Zhang, Chuanliang; Dong, Guozhen; Wu, Xiao; Chen, Jin; Wang, Yanqing; Gong, Liyan; Yang, Xianmin; Shi, Yiying; Gu, Zongwen; Gao, Xiang; Zheng, Yaning; Wu, Han; Zheng, Ke; Liu, Xiaochun; Gu, Yuchao","year":2025,"journal":"Journal of medicinal chemistry, 68(11), 11174-11187","doi":"10.1021/acs.jmedchem.5c00147","pmid":"40458949","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"By conjugating a long-chain fatty acid to the N-terminus and a medium-chain fatty acid to Lys2 of the BimBH3 peptide, the optimized analogue D6 achieved:\n\n- Potent dual PTPN1/2 inhibition (IC50 = 107.6 nM for PTPN1, 3375 nM for PTPN2)\n- 40-fold improved DPP-IV stability over the parent peptide\n- Plasma half-life >200 hours in rats after subcutaneous injection\n- Efficient cell permeability and uptake for intracellular target engagement\n- Restored insulin signaling in HepG2 liver cells\n- Once-weekly glycemic control in db/db diabetic mice","whyItMatters":"PTPN1 and PTPN2 are \"undruggable\" intracellular targets that negatively regulate insulin signaling. Small molecule inhibitors have failed due to selectivity issues. This dual fatty acid peptide approach solves the twin problems of cell entry and long duration, potentially creating a new class of insulin-sensitizing drugs for type 2 diabetes.","specificNumbers":"","methodology":"Researchers systematically explored dual fatty acid conjugation of BimBH3 peptides, testing different chain lengths and attachment positions. Lead compounds were evaluated for PTPN1/2 inhibition potency, DPP-IV resistance, cell permeability, pharmacokinetics in rats, and efficacy in db/db diabetic mice. Molecular docking studies characterized binding interactions with PTPN1/2 active sites.","limitations":"Preclinical study in rats and mice only. The >200 hour half-life in rats may not translate directly to humans. PTPN2 inhibition raises immune safety concerns since PTPN2 regulates immune responses. The cell permeability mechanism and potential off-target effects need further characterization. Manufacturing scalability of dual-conjugated peptides was not addressed."},{"rthcId":"RPEP-14486","title":"Gut microbiota dysbiosis exacerbates heart failure by the LPS-TLR4/NF-κB signalling axis: mechanistic insights and therapeutic potential of TLR4 inhibition.","authors":"Zhang, Chunlei; Teng, Xiaodong; Cao, Qiuhang; Deng, Yanyan; Yang, Mo; Wang, Lei; Rui, Daorong; Ling, Xiu; Wei, Cao; Chen, Yue; Lu, Dasheng; Zhang, Hongxiang","year":2025,"journal":"Journal of translational medicine, 23(1), 762","doi":"10.1186/s12967-025-06821-8","pmid":"40640887","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14487","title":"Peptide Profile Changes in Buffalo Milk Cheese during Different Storage Periods and Characterization of Novel Bioactive Peptides through Peptidomics.","authors":"Zhang, Dan; Yu, Mengyi; Dong, Wenming; Yan, Guanghui; Shi, Yanan; Huang, Aixiang; Wang, Xuefeng","year":2025,"journal":"Journal of agricultural and food chemistry, 73(1), 571-583","doi":"10.1021/acs.jafc.4c09837","pmid":"39772711","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14488","title":"A review of immunometabolic crosstalk in PCOS-related pregnancy loss: mechanisms and emerging therapeutic strategies.","authors":"Zhang, Feng; Wu, Jian; Ge, Liping; Huang, Ying; Huang, Yawen","year":2025,"journal":"Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology, 41(1), 2600160","doi":"10.1080/09513590.2025.2600160","pmid":"41384809","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14489","title":"A preliminary analysis of integrating thymosin α1 into concurrent chemoradiotherapy and consolidative immunotherapy in unresectable locally advanced non-small cell lung cancer.","authors":"Zhang, Hao-Ting; Liu, Fang-Jie; Wang, Da-Quan; Xiong, Yi-Xin; Zhao, Yuan-Yuan; He, Wen-Zhuo; Zhang, Peng-Xin; Zheng, Shi-Yang; Xia, Biao; Situ, Yu; Wang, Meng-Ru; Liu, Qian-Wen; Hu, Yi; Xia, Liang-Ping; Qiu, Bo; Liu, Hui","year":2025,"journal":"Translational lung cancer research, 14(7), 2710-2722","doi":"10.21037/tlcr-2025-190","pmid":"40799433","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14490","title":"ACE inhibitory effect and saltiness-enhancing properties of chicken-derived umami peptides: Digestive stability, inhibition kinetics, multiple ligand docking and central composite design.","authors":"Zhang, Haotong; Liang, Li; Sun, Baoguo; Yang, Rui; Liu, Zunying; Mao, Xiangzhao; Zhang, Yuyu","year":2025,"journal":"Food chemistry, 464(Pt 1), 141634","doi":"10.1016/j.foodchem.2024.141634","pmid":"39437530","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Two chicken-derived umami peptides were identified with dual functionality:\n\n- DGGRYY: ACE inhibition IC50 = 28.71 μM (potent)\n- NEFGYSNR: ACE inhibition IC50 = 283.24 μM (moderate)\n\nBoth peptides demonstrated:\n- Good pH and thermal stability (suitable for food processing)\n- Retention of ACE-inhibitory activity after simulated gastrointestinal digestion (DGGRYY: ~53%, NEFGYSNR: ~57%)\n- Uncompetitive ACE inhibition pattern (binding outside the active pocket)\n- Key binding sites: Trp59, Tyr62, Asp121, Arg124, Ser516\n- Saltiness enhancement in 0.1-0.3% NaCl solutions, compensating for palatability loss from salt reduction","whyItMatters":"Excessive salt intake affects billions of people worldwide and is a leading risk factor for hypertension and cardiovascular disease. Simply reducing salt makes food taste bland, leading to poor compliance. These chicken-derived peptides offer a potential solution: food ingredients that simultaneously enhance salty taste (so less salt is needed) and inhibit ACE (directly lowering blood pressure). This dual-function approach from a natural, food-grade source could be incorporated into everyday food products.","specificNumbers":"","methodology":"Peptides were screened from chicken protein hydrolysates for ACE-inhibitory activity. IC50 values were determined through enzyme inhibition assays. Stability was tested under varying pH and temperature conditions. Simulated gastrointestinal digestion assessed in vivo survival. Inhibition kinetics determined the mechanism, and multiple ligand molecular docking identified binding sites. Sensory analysis with central composite design evaluated saltiness enhancement and palatability in reduced-salt solutions.","limitations":"All results are from in vitro experiments and sensory panels — no animal or human clinical data exist for blood pressure effects. The ACE-inhibitory activity measured in a test tube may not translate to meaningful blood pressure reduction when consumed as food. The digestive stability tests used simulated conditions that may not fully replicate human digestion. Sensory evaluation was limited to NaCl solutions rather than complex food matrices. The peptides' bioavailability (absorption into bloodstream) was not assessed."},{"rthcId":"RPEP-14491","title":"Collagen peptides promote skin collagen synthesis by modulating the gut microbiota and activating the TGF-β pathway.","authors":"Zhang, Haowen; Yao, Zongliang; Song, Yang; Hua, Qinglian; Geng, Xin; Zhou, Fan; Li, Qingcui; Li, Zuozhen; Luo, Zhen; Sun, Jin; Qi, Ce; Li, Duo","year":2025,"journal":"Food & function, 16(13), 5326-5344","doi":"10.1039/d5fo01649e","pmid":"40497369","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14492","title":"First-in-Human Study on Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Escalating Doses of HEC88473, a Novel Dual GLP-1 and FGF21 Receptor Agonist in Healthy and Obese Chinese Subjects.","authors":"Zhang, Hong; Li, Qianqian; Chen, Hong; Guo, Lingfeng; Li, Jing; Xie, Can; Yan, Jiangyu; Ding, Yanhua","year":2025,"journal":"BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy, 39(3), 477-486","doi":"10.1007/s40259-025-00715-3","pmid":"40175670","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"HEC88473 is an Fc fusion protein that combines GLP-1 and FGF21 activity in a single molecule. In this phase 1 single-ascending dose trial:\n\n- Pharmacokinetics: The drug splits into two active components after dosing — Fc-GLP-1 (half-life 66.5-119.5 hours) and Fc-FGF21 (half-life 28.4-41.6 hours), with peak levels at 12-14 hours\n- Blood sugar: At doses ≥5.1 mg, glucose decreased during oral glucose tolerance tests on days 3 and 7. Maximum reduction was -1.829 mmol/L (placebo-adjusted) at 47.6 mg\n- Adiponectin: At doses ≥10.2 mg, levels increased dose-dependently, up to 90.71% from baseline at 62.9 mg\n- Triglycerides: At doses ≥17.0 mg, significant dose-dependent reductions up to -43.01% from baseline at 62.9 mg\n- Safety: Well tolerated; most adverse events were mild GI disorders","whyItMatters":"The metabolic drug race is moving beyond single-target approaches. While GLP-1 drugs are effective for blood sugar and weight, adding FGF21 activity could independently improve lipid metabolism and liver health. HEC88473 represents a new strategy: combining an incretin with a metabolic growth factor. The triglyceride and adiponectin effects from a single dose are particularly notable and could be especially relevant for patients with metabolic syndrome or fatty liver disease.","specificNumbers":"","methodology":"This was a phase 1, single-ascending dose trial (NCT05943886) in healthy and obese Chinese subjects. Participants received single subcutaneous doses of HEC88473 ranging from 0.5 to 62.9 mg or placebo. Researchers measured serum drug concentrations over time (pharmacokinetics), and tracked blood glucose (via oral glucose tolerance test), lipid levels, and adiponectin (pharmacodynamics). Safety was monitored throughout.","limitations":"This was a single-dose phase 1 study focused on safety and pharmacokinetics, not efficacy. The sample size was not disclosed in the abstract. Only Chinese subjects were enrolled, so results may not generalize to other populations. No weight loss data was reported (single-dose studies are too short to measure weight effects). The long-term safety and efficacy of repeated dosing remain unknown."},{"rthcId":"RPEP-14493","title":"Functionalized Nanofinger Enhances Pretrained Language Model Performance for Ultrafast Early Warning of Heart Attacks.","authors":"Zhang, Hongming; Liu, Zerui; Sun, Heming; Wang, Yunxiang; Hsu, Ting-Hao; Hossain, Sushmit; Hiramony, Nishat Tasnim; Roy, Himaddri; Zhou, Hao; Tan, Matthew; Liu, Edward J; Wang, Yihao; Liu, Fanxin; Wu, Wei","year":2025,"journal":"ACS applied bio materials, 8(8), 6970-6980","doi":"10.1021/acsabm.5c00699","pmid":"40684459","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14494","title":"Improved myocardial mitochondrial energy metabolism in rats with chronic heart failure by modifying fatty acid oxidation using an extract of sand-fired aconite (Jianchang gang processing).","authors":"Zhang, Hongtao; Huang, Yi; Yang, Songhong; Gong, Feipeng; Gu, Yuncheng; Xie, Qin; Ye, Yanrong; Lu, Xingmei; Zhong, Lingyun","year":2025,"journal":"Frontiers in pharmacology, 16, 1600410","doi":"10.3389/fphar.2025.1600410","pmid":"41019998","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14495","title":"Inherently anti-metastatic peptide hydrogels for sonodynamic-amplified ferroptosis in cancer therapy.","authors":"Zhang, Hongxia; Wang, Yamei; Jiang, Mengmeng; Wang, Kunyu; Yan, Jingru; Li, Gongyu; Zheng, Zhen","year":2025,"journal":"Materials today. Bio, 32, 101688","doi":"10.1016/j.mtbio.2025.101688","pmid":"40206142","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14496","title":"Glucagon-like peptide-1 receptor PET/CT with 68Ga-exendin-4 for localizing insulinoma: a real-world, single-center study.","authors":"Zhang, Hongzhe; Pan, Qingqing; Liu, Silu; Feng, Jie; Yu, Miao; Li, Naishi; Xu, Qiang; Han, Xianlin; Li, Fang; Luo, Yaping","year":2025,"journal":"European journal of nuclear medicine and molecular imaging, 52(12), 4487-4496","doi":"10.1007/s00259-025-07298-9","pmid":"40310561","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14497","title":"Diabetic kidney disease: from pathogenesis to multimodal therapy-current evidence and future directions.","authors":"Zhang, Hui; Wang, Keding; Zhao, Hairui; Qin, Bowen; Cai, Xiaojing; Wu, Manyi; Li, Junhua; Wang, Jielian","year":2025,"journal":"Frontiers in medicine, 12, 1631053","doi":"10.3389/fmed.2025.1631053","pmid":"40861214","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14498","title":"Revealing Novel Angiotensin-Converting Enzyme (ACE)-Inhibitory Peptides From Mackerel Hydrolysates and Potential Antihypertensive Mechanism Using Virtual Screening and Network Pharmacology Analysis.","authors":"Zhang, Hui; Wang, Chenxu; Wang, Fang; Zhang, Xinyu; Wang, Yue; Xie, Youping; Wang, Baobei; Zheng, Zong-Ping","year":2025,"journal":"Journal of food science, 90(12), e70767","doi":"10.1111/1750-3841.70767","pmid":"41392825","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14499","title":"Elevated blood levels of liver-expressed antimicrobial peptide 2 in patients with insulinoma and its expression in insulinomas.","authors":"Zhang, Jia-Lei; Tong, An-Li; Feng, Yun-Lu; Zhao, Da-Chun; Zhong, Ling; Gao, Yin-Jie; Song, Yu-Li; Zhang, Tai-Ping; Li, Ming; Chen, Yuan-Jia","year":2025,"journal":"Frontiers in endocrinology, 16, 1685806","doi":"10.3389/fendo.2025.1685806","pmid":"41488138","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14500","title":"HNP-1: From Structure to Application Thanks to Multifaceted Functions.","authors":"Zhang, Jiaqi; Liu, Zhaoke; Zhou, Zhihao; Huang, Zile; Yang, Yifan; Wu, Junzhu; Liu, Yanhong","year":2025,"journal":"Microorganisms, 13(2)","doi":"10.3390/microorganisms13020458","pmid":"40005828","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"HNP-1, produced primarily by human neutrophils, exhibits broad-spectrum antimicrobial activity against both bacteria and viruses. The review identified several key aspects:\n\n• HNP-1 combats pathogens without leading to the resistance patterns seen with traditional antibiotics\n• The peptide has multiple functions beyond direct antimicrobial killing, including immune regulatory roles\n• Mass production has been a major barrier to clinical use — microbial biosynthesis systems offer a cost-effective alternative to human extraction\n• Recent studies have revealed HNP-1's endogenous bactericidal mechanism, advancing understanding of how it kills pathogens\n• The peptide's gene expression, distribution, and regulatory elements controlling its production are now better understood","whyItMatters":"Antibiotic resistance is one of the biggest threats to global health, with drug-resistant infections killing over a million people annually. HNP-1 represents a fundamentally different approach — using the body's own antimicrobial peptide as a therapeutic agent. Because HNP-1 kills bacteria by disrupting their membranes (rather than targeting specific proteins like antibiotics do), bacteria have much more difficulty developing resistance. If production challenges can be solved, HNP-1 could become a powerful weapon against drug-resistant infections.","specificNumbers":"","methodology":"This was a comprehensive narrative review examining published literature on HNP-1, covering its molecular structure, gene expression, tissue distribution, immune functions, antimicrobial mechanisms, biosynthesis methods, and potential clinical applications. The review integrated studies on both the basic biology of HNP-1 and applied research on production methods.","limitations":"This is a narrative review that summarizes existing knowledge rather than presenting new data. The clinical application of HNP-1 remains theoretical — no human clinical trials are reported. The mass production challenge, while being addressed through microbial biosynthesis, has not been fully solved. The review may not cover all recent studies comprehensively. Additionally, antimicrobial peptides can have off-target effects (e.g., toxicity to host cells at high concentrations) that are not deeply explored."},{"rthcId":"RPEP-14501","title":"Effects of semaglutide in patients with chronic ankle instability: evidence from a prospective cohort.","authors":"Zhang, Jieyuan; Wang, Cheng; Wang, Jiazheng; Gu, Wenqi; Wang, Haiqing; Zhu, Hongyi; Ma, Xin; Shi, Zhongmin","year":2025,"journal":"Journal of orthopaedic surgery and research, 20(1), 243","doi":"10.1186/s13018-025-05664-9","pmid":"40050929","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14502","title":"An effective cell-penetrating peptide-based loading method to extracellular vesicles and enhancement in cellular delivery of drugs.","authors":"Zhang, Jin; Su, Ning; Liu, Wei; Li, Mengran; Zheng, Haoyang; Li, Bing; Jin, Xue; Gao, Mingxia; Zhang, Xiangmin","year":2025,"journal":"Analytical and bioanalytical chemistry, 417(8), 1449-1459","doi":"10.1007/s00216-025-05742-1","pmid":"39836222","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14503","title":"Naoxintong capsule attenuates heart damage after ischemic stroke via Nuclear factor-κB / Pyrin domain-containing protein 3 / Caspase-1 signaling.","authors":"Zhang, Jing; Li, Yu; Chang, Mengli; Lei, Yuxin; Xu, He; Zhang, Yi; Xu, Jing; Zhang, Jingjing; Tang, Shihuan","year":2025,"journal":"Journal of ethnopharmacology, 341, 119240","doi":"10.1016/j.jep.2024.119240","pmid":"39733802","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14504","title":"Long-term Efficacy, Survival, and Toxicity of Peptide Receptor Radionuclide Therapy in Patients With Refractory Meningioma.","authors":"Zhang, Jingjing; Li, Deling; Shi, Mengqi; Jakobsson, Vivianne; Jia, Wang; Kulkarni, Harshad R; Schuchardt, Christiane; Baum, Richard P","year":2025,"journal":"Clinical nuclear medicine, 50(6), 508-516","doi":"10.1097/RLU.0000000000005845","pmid":"40320628","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14505","title":"Functionalized transdermal collagen mimetic peptides for efficient repair of subacute aged skin.","authors":"Zhang, Jingting; Liu, Guangyu; Yang, Yi; Xie, Yi; Yao, Linyan; Xiao, Jianxi","year":2025,"journal":"Biomaterials science, 13(19), 5495-5511","doi":"10.1039/d5bm00940e","pmid":"40828418","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14506","title":"Fabrication of BMSCs-affinity peptide functionalized blended hyaluronic acid/polydopamine nanofibrous scaffolds to controlled Mg ion release and improved osteogenic differentiations for accelerating bone regeneration.","authors":"Zhang, Jingzhe; Wang, Xinkun; Fu, Xinbiao; Li, Ye","year":2025,"journal":"Journal of biological engineering, 19(1), 72","doi":"10.1186/s13036-025-00529-5","pmid":"40731291","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14507","title":"Design, synthesis, and structure-activity relationship study of novel GLP-1/GIP/GCG triple receptor agonists.","authors":"Zhang, Jinhua; Xu, Hongjiang; Dong, Yuanzhen; Feng, Jun; Li, Ruifang","year":2025,"journal":"European journal of medicinal chemistry, 298, 118024","doi":"10.1016/j.ejmech.2025.118024","pmid":"40749257","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14508","title":"Gut Hormones and Postprandial Metabolic Effects of Isomaltulose vs. Saccharose Consumption in People with Metabolic Syndrome.","authors":"Zhang, Jiudan; Sonnenburg, Dominik; Kabisch, Stefan; Theis, Stephan; Kemper, Margrit; Pivovarova-Ramich, Olga; Tricò, Domenico; Rohn, Sascha; Pfeiffer, Andreas F H","year":2025,"journal":"Nutrients, 17(15)","doi":"10.3390/nu17152539","pmid":"40806123","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14509","title":"Novel Dual and Triple Agonists Targeting GLP-1, GIP, Glucagon, and GDF15 for Type 2 Diabetes and Obesity Management.","authors":"Zhang, Jiudan; Sanan, Shriya; Csanalosi, Marta; Zheng, Chao; Pfeiffer, Andreas F H","year":2025,"journal":"Endocrinology, 166(11)","doi":"10.1210/endocr/bqaf130","pmid":"40817831","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review synthesizes evidence for several emerging multi-agonist peptide drug classes:\n\n- GLP-1/GIP dual agonists (e.g., tirzepatide) have already demonstrated superior efficacy over GLP-1 monotherapy\n- GLP-1/glucagon dual agonists leverage glucagon's energy-expenditure effects while offsetting its glucose-raising activity with GLP-1's insulin-promoting action\n- GLP-1/GIP/glucagon triple agonists (e.g., retatrutide) target all three receptors for potentially maximal metabolic benefit\n- GDF15-based approaches represent a newer pathway that reduces appetite through brainstem signaling\n- Beyond metabolic effects, these agents may offer cardioprotective and anti-inflammatory benefits","whyItMatters":"The obesity and diabetes drug market is undergoing its most transformative period in history. Understanding the pipeline of multi-agonist peptides is essential for clinicians, researchers, and patients alike. Each additional receptor target adds efficacy but also complexity — knowing which combinations are most promising and what safety trade-offs exist will guide the next decade of metabolic pharmacotherapy.","specificNumbers":"","methodology":"Narrative review of published preclinical and clinical evidence for novel dual and triple peptide agonists targeting GLP-1, GIP, glucagon, and GDF15 receptors. The review focuses on mechanisms of action, clinical efficacy data, and safety profiles.","limitations":"As a review, no original data are presented. Many of the dual and triple agonists discussed are in early to mid-stage clinical development, and long-term efficacy and safety data are limited. The review explicitly excludes amylin analogs and other peptide approaches, so it does not cover the full landscape. The safety profiles of multi-agonist peptides are still being established, particularly for cardiovascular and gastrointestinal endpoints."},{"rthcId":"RPEP-14510","title":"Semaglutide ameliorates metabolic disorders in offspring via regulation of oocyte ROS of pre-pregnancy obesity mice.","authors":"Zhang, Jun-Kai; Li, Xiao-Ping; Tang, Yang; Zeng, Li-Ping; Liu, Xuan; Zhang, Jian-Li; Chen, Cai-Yu; Zheng, Shuo; Liu, Zhi-Zhao; Gong, Xue; Jose, Pedro A; Guo, Li; Zeng, Chun-Yu","year":2025,"journal":"Acta pharmacologica Sinica, 46(6), 1664-1675","doi":"10.1038/s41401-025-01501-1","pmid":"39984623","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14511","title":"Identification of disease subtypes associated with prognosis in patients with intermediate-high-risk pulmonary embolism based on hierarchical cluster analysis.","authors":"Zhang, Lihui; Wang, Xincai; Pan, Xiaobin; Zhang, Shujuan; Shi, Songchang; Lin, Wei","year":2025,"journal":"Journal of thoracic disease, 17(9), 6508-6515","doi":"10.21037/jtd-2025-556","pmid":"41158372","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14512","title":"Liraglutide attenuates autoimmune myocarditis by inhibiting NLRP3 and NF-κb pathways.","authors":"Zhang, Lijuan; Han, Lishuai; Lu, Yang; Chen, Quanzhou","year":2025,"journal":"Scientific reports, 15(1), 27274","doi":"10.1038/s41598-025-12715-y","pmid":"40715315","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Liraglutide significantly reduced myocarditis severity, as shown by lower heart weight/body weight ratio, reduced serum cardiac troponin T, decreased cardiac fibrosis, and diminished inflammatory infiltration. Echocardiography confirmed improved left ventricular function. Immunofluorescence and RT-qPCR showed decreased T-cell and macrophage infiltration with reduced pro-inflammatory cytokine expression. RNA sequencing identified the NLRP3 inflammasome and NF-κB pathways as the key targets modulated by liraglutide.","whyItMatters":"Myocarditis has gained increased attention since it was identified as a rare side effect of both COVID-19 infection and mRNA vaccines. Current treatments are limited to immunosuppressants with significant side effects. Finding that an already-approved, well-tolerated drug like liraglutide can reduce heart inflammation through specific pathways could quickly translate to clinical trials. The NLRP3/NF-κB mechanism also connects to the broader understanding of GLP-1RA anti-inflammatory effects seen across multiple organ systems.","specificNumbers":"","methodology":"Preclinical study using a mouse model of autoimmune myocarditis treated with liraglutide. Assessment included heart weight/body weight ratio, serum troponin T, echocardiography for cardiac function, histological staining for fibrosis and inflammation, immunofluorescence for immune cell infiltration, RT-qPCR for cytokine expression, and RNA sequencing for pathway analysis.","limitations":"This is a mouse study using an induced autoimmune myocarditis model, which may not fully represent human myocarditis (often viral or idiopathic). Specific animal numbers, liraglutide doses, and treatment duration were not detailed in the abstract. The RNA sequencing identified pathways but direct causation (e.g., through specific inhibitors) was not confirmed. Human myocarditis has varied causes and presentations that a single mouse model cannot capture."},{"rthcId":"RPEP-14513","title":"A Validated, Stability-Indicating HPLC Method for the Simultaneous Determination of Five Related Substances in Liraglutide Drug Substance.","authors":"Zhang, Lixiang; Li, Xinyu; Zhang, Jiansong; Wang, Xiao; Fu, Yuqing","year":2025,"journal":"Biomedical chromatography : BMC, 39(7), e70118","doi":"10.1002/bmc.70118","pmid":"40442972","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14514","title":"Role of Pulmonary Neuroendocrine Cells in COPD.","authors":"Zhang, Lulu; Tu, Bo; Xue, Qingliang","year":2025,"journal":"Immunological investigations, 54(8), 1294-1308","doi":"10.1080/08820139.2025.2547690","pmid":"40915969","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14515","title":"Increased Dipeptidyl Peptidase-4 Promotes Adipose Inflammation and Dysfunction in Mice Under Chronic Stress.","authors":"Zhang, Meiping; Wang, Huazhen; Li, Xiangdan; Shu, Shangzhi; Piao, Jinshun; Yue, Xueling; Zhao, Songzhen; Li, Miao; Jin, Xianglan; Nan, Yongshan; Cheng, Xian Wu","year":2025,"journal":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 39(15), e70893","doi":"10.1096/fj.202502147R","pmid":"40742315","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14516","title":"GLP-1 receptor agonist semaglutide ameliorates motor deficits and tau pathology in the rTg4510s mouse model.","authors":"Zhang, Meng-Wei; Zhou, Wan-Yi; Li, Xin-Yi; Xu, Zhi-Heng; Lin, Hua-Mei; Tang, Yi-Lin; Zhao, Jue; Chen, Chen; Liu, Feng-Tao; Sun, Yi-Min; Zuo, Chuan-Tao; Wu, Jian-Jun; Wang, Jian; Yu, Wen-Bo","year":2025,"journal":"Neuropharmacology, 280, 110659","doi":"10.1016/j.neuropharm.2025.110659","pmid":"40882702","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14517","title":"Predicted peptide scaffolds for drug screening in endometrial cancer organoids.","authors":"Zhang, Mengli; Wan, Yuan; Li, Dingxi","year":2025,"journal":"Scientific reports, 15(1), 37408","doi":"10.1038/s41598-025-21282-1","pmid":"41145641","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14518","title":"Cardiovascular and brain effects of liraglutide in transthyretin amyloidosis (ATTR) mice models.","authors":"Zhang, Mengqing; Li, Zonglin; Cai, Xiaoling; Lv, Fang; Wen, Xin; Guo, Chengcheng; Lin, Chu; Ji, Linong","year":2025,"journal":"International journal of medical sciences, 22(13), 3229-3241","doi":"10.7150/ijms.112264","pmid":"40765557","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"High-throughput screening and microscale thermophoresis confirmed that liraglutide has high affinity for and directly binds to transthyretin (TTR) protein. In humanized ATTRv mice carrying the Val50Met mutation, 28 days of liraglutide treatment (0.3 mg/kg/day) significantly decreased TTR protein content in brain tissue compared to placebo.\n\nHowever, cardiovascular endpoints showed no benefit. Plasma BNP (heart failure marker), cardiac fibrosis markers (Col1a1 and TGFβ1 expression), and pathological measures (right ventricular collagen percentage, ventricular septum thickness, left ventricular wall thickness, and left ventricular internal diameter) were all statistically comparable between liraglutide and placebo groups.","whyItMatters":"Transthyretin amyloidosis is a serious and progressive disease with limited treatment options. The finding that a widely available GLP-1 receptor agonist can directly bind transthyretin and reduce its brain accumulation is novel and opens a potential new therapeutic avenue — particularly for the neurological aspects of the disease. The lack of cardiac benefit in this short study doesn't rule out longer-term effects and highlights the need for further research.","specificNumbers":"","methodology":"Researchers first used high-throughput screening to identify liraglutide's drug targets and microscale thermophoresis to confirm direct binding to TTR. They then constructed humanized mouse models: RBP4/TTR (normal) and RBP4/TTR-Val50Met (ATTRv disease) mice. Mice were treated with liraglutide (0.3 mg/kg/day) or placebo for 28 days. Outcomes were assessed using glucose tolerance tests, plasma BNP measurement, western blot, ELISA, RT-qPCR, and pathological tissue staining.","limitations":"This was a short-term (28-day) animal study using genetically engineered mice, which may not fully replicate human disease progression. The sample size of mice is not specified in the abstract. The lack of cardiac benefit could be due to the short treatment duration or the dose used. The humanized mouse model, while more relevant than standard mice, still has inherent differences from human disease. Only one dose level was tested."},{"rthcId":"RPEP-14519","title":"Real-world observations of GLP-1 receptor agonists and SGLT-2 inhibitors as potential treatments for Alzheimer's disease.","authors":"Zhang, Pengyue; Mao, Chengsheng; Sun, Anna; Yang, Yuedi; Hou, Yuan; Fu, Zhimin; Babak, Tousi; Leverenz, James B; Pieper, Andrew A; Luo, Yuan; Cummings, Jeffrey; Cheng, Feixiong","year":2025,"journal":"Alzheimer's & dementia : the journal of the Alzheimer's Association, 21(9), e70639","doi":"10.1002/alz.70639","pmid":"40898408","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14520","title":"Bacillus subtilis-Derived Surfactin Alleviates Offspring Intestinal Inflammatory Injuries Through Breast Milk.","authors":"Zhang, Qi; Xie, Shuang; Zhong, Qiu; Zhang, Xinyue; Luo, Liufang; Yang, Qian","year":2025,"journal":"Nutrients, 17(6)","doi":"10.3390/nu17061009","pmid":"40290006","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14521","title":"CCN5 suppresses injury-induced vascular restenosis by inhibiting smooth muscle cell proliferation and facilitating endothelial repair via thymosin β4 and Cd9 pathway.","authors":"Zhang, Qi; Li, Hongda; Zhuang, Tao; Xu, Lehua; Wu, Wenrun; Pi, Jingjiang; Zhu, Pengxiong; Geng, Liang; Duan, Yunhao; Xu, Jianfei; Yue, Jinnan; Liu, Xiuxiang; He, Chenlong; Chen, Xiaoli; Ruan, Chengchao; Zhuang, Shougang; Liu, Zhongmin; Wang, Yilong; Zhang, Lin; Liu, Jie; Zhang, Yuzhen","year":2025,"journal":"European heart journal, 46(17), 1645-1658","doi":"10.1093/eurheartj/ehae911","pmid":"39873228","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14522","title":"GLP-1RAs regulate lipid metabolism and induce autophagy through AMPK/SIRT1 pathway to improve NAFLD.","authors":"Zhang, Qiang; Wang, Jingyuan; Hu, Xiaojin; Lu, Wei; Cao, Yang; Niu, Chunyan; Yue, Hongqin","year":2025,"journal":"Prostaglandins & other lipid mediators, 178, 106987","doi":"10.1016/j.prostaglandins.2025.106987","pmid":"40180281","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Liraglutide significantly reversed free fatty acid-induced hepatocyte steatosis (fatty liver cells) through two complementary mechanisms. First, it regulated lipid metabolism enzymes: decreasing lipogenesis proteins (FAS, ACC1) that make new fat, while increasing lipolysis proteins (ATGL, HSL, LAL) that break down stored fat.\n\nSecond, liraglutide enhanced autophagy — the cellular self-digestion process that clears accumulated lipid droplets. Both effects were AMPK-dependent and required SIRT1: when SIRT1 was knocked down, liraglutide could no longer induce autophagy or reduce lipid accumulation. This establishes the AMPK/SIRT1 axis as the critical mediator of GLP-1 receptor agonist activity against hepatic steatosis.","whyItMatters":"NAFLD affects approximately 25% of people globally and is the fastest-growing indication for liver transplantation. No drug has been specifically approved for NAFLD in most countries, though GLP-1 drugs are increasingly used off-label. This study reveals exactly how liraglutide works against fatty liver at the molecular level — through the AMPK/SIRT1 pathway controlling both fat metabolism and cellular cleanup. Understanding this mechanism could help develop more targeted treatments and identify which NAFLD patients are most likely to respond to GLP-1 therapy.","specificNumbers":"","methodology":"The study used hepatocyte cell lines (HepG2) treated with free fatty acids to model NAFLD in vitro. Liraglutide was applied to test its effect on fat accumulation. Western blotting measured expression of lipogenesis proteins (FAS, ACC1), lipolysis proteins (ATGL, HSL, LAL), and autophagy markers. SIRT1 knockdown experiments using gene silencing confirmed the pathway dependency. AMPK activation was assessed to establish the signaling cascade.","limitations":"The study used HepG2 cell lines, which are hepatocellular carcinoma-derived cells and may not fully represent normal hepatocyte biology. No in vivo animal model was used to confirm the cell culture findings. The AMPK/SIRT1 pathway may not be the only mechanism by which GLP-1 drugs improve NAFLD — weight loss, reduced insulin resistance, and direct hepatic effects through other pathways also contribute. The free fatty acid model of steatosis is simplified compared to the complex pathology of human NAFLD/NASH."},{"rthcId":"RPEP-14523","title":"Peptides as Master Keys to Skin Aging.","authors":"Zhang, Qianqian; Liu, Zijian; Shu, Peng; Jiang, Ligang; Ding, Wenfeng","year":2025,"journal":"Skin pharmacology and physiology, 38(5-6), 217-231","doi":"10.1159/000547734","pmid":"40875756","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies three major innovations in peptide-based anti-aging strategies: (1) environment-responsive peptides that can be triggered by specific skin conditions like pH changes or oxidative stress, (2) biomimetic peptides designed to mimic the function of natural skin proteins and signaling molecules, and (3) advanced nano-delivery systems that overcome the skin barrier to deliver peptides effectively to target cells.\n\nThe integration of chronobiology (studying how aging processes vary with circadian rhythms) and multi-omics approaches (genomics, proteomics, metabolomics) is further refining peptide-based interventions toward personalized anti-aging treatments.","whyItMatters":"The global anti-aging skincare market is massive, but many products lack scientific rigor. This review highlights how peptide science is moving beyond simple cosmetic claims toward molecularly targeted interventions that address the root causes of skin aging — cellular senescence, collagen breakdown, oxidative stress, and inflammation. The convergence of peptide design with nanotechnology and precision medicine could transform how aging skin is treated.","specificNumbers":"","methodology":"Narrative review of recent research on peptide-based therapeutic strategies for skin aging, covering the molecular mechanisms of skin aging, innovative peptide designs, delivery technologies, and the application of chronobiology and multi-omics analysis to personalized anti-aging approaches.","limitations":"This is a review article that discusses emerging strategies, many of which are at early stages of development. The abstract does not cite specific clinical trial data for the peptide strategies discussed. The translation from laboratory peptide design to effective commercial products faces challenges in stability, delivery, and regulatory approval. The line between cosmetic claims and therapeutic effects is not clearly delineated."},{"rthcId":"RPEP-14524","title":"The Contribution of Human Antimicrobial Peptides to Fungi.","authors":"Zhang, Qiaoxi; Choi, Kitman; Wang, Xiaoyue; Xi, Liyan; Lu, Sha","year":2025,"journal":"International journal of molecular sciences, 26(6)","doi":"10.3390/ijms26062494","pmid":"40141139","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14525","title":"Population profile and glycemic control following initiation or switch of injectable therapies in Tianjin, China: A real-world retrospective cohort study of adults with type 2 diabetes.","authors":"Zhang, Qiumei; Fan, Yaqing; Liu, Xixi; Zhang, Minlu; Zhang, Jiewen; Du, Qin; Kang, Lei; Chen, Liming","year":2025,"journal":"Journal of diabetes investigation, 16(5), 842-851","doi":"10.1111/jdi.14415","pmid":"39899440","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14526","title":"Injectable antibacterial drug-free hydrogel dressing enabled by a bioactive peptide-mimicking synthetic peptidyl polymer.","authors":"Zhang, Rong; Tian, Yongchang; Cui, Jiaming; Hamley, Ian W; Xiao, Chunsheng; Chen, Li","year":2025,"journal":"Acta biomaterialia, 193, 143-156","doi":"10.1016/j.actbio.2025.01.008","pmid":"39793746","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14527","title":"Bovine Collagen Peptide Improves Hypoxia Tolerance and Anti-Fatigue Capacity in Hypobaric Hypoxic Environments: A Combined Animal and Human Study.","authors":"Zhang, Rui; Fu, Zi-Xian; Xiong, Jun-Bin; Guo, Wei-Hong; Shi, Wen-Pu; Jia, Bin; Shi, Jun-Ling; Yin, Da-Chuan","year":2025,"journal":"Food science & nutrition, 13(5), e70278","doi":"10.1002/fsn3.70278","pmid":"40376602","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In mice at simulated 4,000 m altitude, bovine collagen peptide (BCP) supplementation for 5 days produced an 8-fold increase in rotarod (balance/endurance) performance compared to controls (p<0.05).\n\nIn human volunteers exercising under hypobaric hypoxic conditions, BCP supplementation significantly improved blood oxygen saturation (SpO2) and physical performance metrics (p<0.001 for key measures). In vitro assays confirmed significant antioxidant activity. The peptide was characterized as rich in glycine, proline, and glutamic acid with confirmed peptide structure via FT-IR spectroscopy.","whyItMatters":"Millions of people travel to or live at high altitudes where reduced oxygen can cause altitude sickness, fatigue, and impaired performance. Finding a safe, food-grade supplement that improves hypoxia tolerance could benefit athletes training at altitude, military personnel, high-altitude workers, and travelers. Collagen peptides are already widely consumed supplements, making translation to practical use straightforward.","specificNumbers":"","methodology":"Two-stage study: (1) Animal stage — mice received BCP for 5 days then performed rotarod tests at simulated 4,000 m altitude. (2) Human stage — volunteers took BCP supplementation and exercised in a hypobaric hypoxic chamber, with SpO2 and performance measures recorded. Peptide characterization included amino acid analysis, dynamic light scattering for particle size, FT-IR spectroscopy for structure confirmation, and in vitro antioxidant assays.","limitations":"The abstract contains truncated statistical data (incomplete p-values and measure descriptions), making it difficult to fully assess the human trial results. The mouse supplementation period was only 5 days, and longer-term effects are unknown. The human trial details (sample size, blinding, control treatment) are not fully described in the abstract. The mechanisms linking antioxidant activity to hypoxia tolerance are correlational, not causally established."},{"rthcId":"RPEP-14528","title":"Sustained Delivery of Liraglutide Using Multivesicular Liposome Based on Mixed Phospholipids.","authors":"Zhang, Runpeng; Yao, Xinyu; Gao, Siqi; Xu, Tingting; Wang, Da; Sha, Luping; Yang, Li","year":2025,"journal":"Pharmaceutics, 17(2)","doi":"10.3390/pharmaceutics17020203","pmid":"40006570","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14529","title":"Quantitative Comparison of Glucagon-Like Peptide-1 Receptor Agonists on Weight Loss in Adults: A Systematic Review and Model-Based Meta-Analysis.","authors":"Zhang, Shaolong; Yu, Boran; Xu, Jiamin; Jin, Siyao; Li, Yanming; Bing, Hao; Li, Jueyu; Ma, Xiangyu; Zhang, Xianhua; Zhao, Libo","year":2025,"journal":"Diabetes technology & therapeutics, 27(6), 422-429","doi":"10.1089/dia.2024.0533","pmid":"39911047","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 17 GLP-1 receptor agonists across 137 trials (310 treatment arms, 56,683 patients), retatrutide 12 mg weekly produced the largest weight reduction (mean -26.56%, 95% CI: -43.89% to -3.01%). Tirzepatide 15 mg weekly was consistently effective across all populations: -22.76% in non-diabetic overweight/obese patients, -11.09% in Caucasian T2D patients, and -4.97% in Asian T2D patients.\n\nHigher baseline body weight predicted better weight loss outcomes, while higher baseline HbA1c predicted better glycemic improvements. For HbA1c reduction, tirzepatide 10 mg and oral orforglipron 10 mg were the most effective agents. The analysis also revealed marked differences in weight loss efficacy between diabetic and non-diabetic populations and between ethnic groups.","whyItMatters":"With the GLP-1 drug market exploding and multiple new agents in development, clinicians and patients need evidence-based comparisons to guide treatment selection. This is one of the most comprehensive quantitative comparisons to date, ranking 17 drugs head-to-head using model-based meta-analysis. The finding that weight loss varies significantly by diabetes status and ethnicity is clinically important for setting realistic expectations.","specificNumbers":"","methodology":"Systematic review and model-based meta-analysis of randomized controlled trials identified from PubMed, Cochrane CENTRAL, and Embase through January 2024. The 137 included trials were divided into three population groups: non-diabetic overweight/obesity, type 2 diabetes Caucasian, and type 2 diabetes Asian. Five mathematical models were used for longitudinal analysis of body weight change and HbA1c change. Covariates including baseline body weight and HbA1c were evaluated for their influence on outcomes.","limitations":"Retatrutide's confidence interval was very wide (-43.89% to -3.01%), reflecting limited trial data for this newer agent. The analysis pooled data across trials with different designs, durations, and populations, which introduces heterogeneity. The three population subgroups are broad categories that don't capture the full diversity of patient characteristics. Data cutoff was January 2024, so more recent trial results are not included. Safety and tolerability were not compared in this analysis."},{"rthcId":"RPEP-14530","title":"Efficacy and Safety of Xinmailong Injection for Chronic Heart Failure: A Systematic Review and Meta-Analysis for Randomized Clinical Trials.","authors":"Zhang, Shu-Wen; Chen, Jia-Ping; Zong, Hui-Qi; Li, Xiang; Liu, Hong-Xu","year":2025,"journal":"Journal of integrative and complementary medicine, 31(10), 876-888","doi":"10.1089/jicm.2025.0031","pmid":"40478767","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14531","title":"Stochastic neuropeptide signals compete to calibrate the rate of satiation.","authors":"Zhang, Stephen X; Kim, Angela; Madara, Joseph C; Zhu, Paula K; Christenson, Lauren F; Lutas, Andrew; Kalugin, Peter N; Sunkavalli, Praneel S; Jin, Yihan; Pal, Akash; Tian, Lin; Lowell, Bradford B; Andermann, Mark L","year":2025,"journal":"Nature, 637(8044), 137-144","doi":"10.1038/s41586-024-08164-8","pmid":"39506113","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Hunger-promoting AgRP neurons release NPY to decrease cAMP in hypothalamic MC4R neurons, while satiety-promoting POMC neurons release αMSH to increase cAMP. Each release event is all-or-none, stochastic, and affects multiple neurons within an approximately 100 µm diameter region.\n\nThe peptides compete: NPY signaling is blunted by high αMSH in the fed state, and αMSH signaling is blunted by high NPY in the fasted state. Eating resolves this competition by simultaneously boosting αMSH and suppressing NPY, sustaining elevated cAMP throughout a meal. This elevated cAMP progressively potentiates excitatory feeding-related synaptic inputs with each bite, gradually promoting satiation over many minutes.","whyItMatters":"Understanding exactly how the brain decides when to stop eating is fundamental to addressing obesity and eating disorders. This study reveals for the first time that neuropeptide competition — not a simple on/off signal — governs satiation. This mechanism could explain why appetite-controlling drugs like GLP-1 agonists work for some people but not others, and could inspire new approaches targeting the NPY-αMSH balance directly.","specificNumbers":"","methodology":"Researchers used live imaging of neuropeptide signaling and cAMP dynamics in MC4R-expressing neurons of the paraventricular hypothalamic nucleus in awake mice. They monitored the release patterns of NPY and αMSH from AgRP and POMC axons respectively, characterizing the spatiotemporal properties of individual release events and measuring downstream effects on cAMP and synaptic transmission during feeding behavior.","limitations":"This is a mouse study, and the detailed neural dynamics may differ in the human brain. The imaging techniques required specialized genetic tools and may not capture the full complexity of peptide interactions in the hypothalamus. The study focused specifically on MC4R neurons in the paraventricular nucleus, and other brain regions involved in feeding were not examined. Long-term changes in this peptide competition (e.g., in obesity) were not studied."},{"rthcId":"RPEP-14532","title":"IL-16 exerts anti-rabies virus effects through CD9 on the surface of viral particles.","authors":"Zhang, Taoping; Xu, Ruixian; Li, Qiang; Jia, Ting; Shi, Wengang; Chen, Lu; Faisal, Mahmood; Gong, Chunlin; Zhao, Dongyi; Dai, Li; Fan, Lu; Song, Yuzhu; Han, Qinqin; Xia, Xueshan; Zhang, Jinyang","year":2025,"journal":"International journal of biological macromolecules, 305(Pt 1), 141042","doi":"10.1016/j.ijbiomac.2025.141042","pmid":"39956243","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14533","title":"Dendritic cell-based vaccine prepared with recombinant Lactococcus lactis eukaryotic-prokaryotic dual expressing OVA enhances antitumor efficacy by both direct and cross-presentation.","authors":"Zhang, Tingting; Huang, Shuai; Liu, Peng; Su, Xiaoqiu; Zou, Jiahe; Wu, Yulin; Li, Yijie; Xu, Yuekang; Li, Jinyao","year":2025,"journal":"International immunopharmacology, 163, 115263","doi":"10.1016/j.intimp.2025.115263","pmid":"40706205","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14534","title":"Strategies to Enhance the Therapeutic Efficacy of GLP-1 Receptor Agonists through Structural Modification and Carrier Delivery.","authors":"Zhang, Tingting; Liu, Sainan; He, Suning; Shi, Linqi; Ma, Rujiang","year":2025,"journal":"Chembiochem : a European journal of chemical biology, 26(8), e202400962","doi":"10.1002/cbic.202400962","pmid":"39744852","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14535","title":"Pharmacotherapy to Prevent Alcohol Relapse in Alcohol-Associated Liver Disease.","authors":"Zhang, Wei; Hwang, Soo Young; Luther, Jay","year":2025,"journal":"Current gastroenterology reports, 27(1), 74","doi":"10.1007/s11894-025-01026-x","pmid":"41258558","tags":[],"studyType":"review","evidenceStrength":"low","keyFinding":"This review examines drugs that can prevent alcohol relapse in patients with alcohol-associated liver disease (ALD). Established medications like naltrexone and acamprosate reduce relapse in general alcohol use disorder but have limited data specifically in liver disease patients. Baclofen is the only drug tested in randomized trials in patients with cirrhosis, showing early benefit but mixed results in later studies.\n\nNotably, emerging peptide-based therapies show early promise: GLP-1 receptor agonists, FGF21 (fibroblast growth factor-21) analogs, and psilocybin are all showing early signals for reducing alcohol use. Despite guideline support, these medications remain dramatically underused due to stigma, lack of provider training, and fragmented care.","whyItMatters":"Alcohol-associated liver disease is a leading cause of liver transplantation, and relapse after abstinence is the primary driver of disease progression and post-transplant failure. The emergence of GLP-1 receptor agonists and FGF21 analogs as potential anti-relapse therapies is particularly significant because these peptide drugs could simultaneously treat metabolic liver disease and reduce alcohol cravings — addressing two problems with one medication class.","specificNumbers":"Established drugs: naltrexone, acamprosate, baclofen · Emerging agents: GLP-1 RAs, FGF21 analogs, psilocybin · pharmacotherapy remains underutilized in ALD","methodology":"This is a narrative review that summarizes the published evidence for pharmacotherapies used to prevent alcohol relapse, with a focus on their application in patients with alcohol-associated liver disease. The authors evaluate both established and emerging drug therapies and discuss barriers to their clinical adoption.","limitations":"As a narrative review, this paper does not present new data or conduct systematic analysis. Most drug evidence comes from general alcohol use disorder populations rather than liver disease patients specifically. The emerging therapies (GLP-1 RAs, FGF21 analogs) are described as having 'early signals' only, meaning robust clinical trial data is still needed."},{"rthcId":"RPEP-14536","title":"Rational construction of porous cobalt nanoparticle integrated nitrogen doped hollow carbon nanostructures for peptide agonist exendin-4 biosensing.","authors":"Zhang, Wei; Natarajan, Bharathi; Kannan, Palanisamy; Medlín, Rostislav; Nicolai, Laurent Christophe; Procházka, Michal; Minar, Jan; Subramanian, Palaniappan","year":2025,"journal":"Biosensors & bioelectronics, 270, 116938","doi":"10.1016/j.bios.2024.116938","pmid":"39566332","tags":[],"studyType":"in vitro","evidenceStrength":"preliminary","keyFinding":"Researchers built a point-of-care electrochemical biosensor using cobalt nanoparticles embedded in nitrogen-doped hollow carbon nanostructures to detect exendin-4, a peptide drug used for type 2 diabetes. The best-performing sensor (Co3O4@HNCNs) detected exendin-4 at concentrations as low as 0.46 picomolar — an extremely sensitive threshold.\n\nThe sensor worked across a detection range of 1.0 to 90.0 pM with a sensitivity of 0.60 μA/pM. When tested on real human blood serum and urine samples, it achieved recovery rates of 96–104%, demonstrating practical accuracy for clinical use.","whyItMatters":"Exendin-4 (the basis for the diabetes drug exenatide/Byetta) is part of the GLP-1 agonist family that has transformed diabetes and obesity treatment. Being able to detect tiny amounts of this peptide in blood or urine could help clinicians monitor drug levels, detect misuse in sports (it's banned by WADA), or verify medication adherence. A point-of-care sensor that works at picomolar sensitivity could bring peptide drug monitoring out of specialized labs and into clinics.","specificNumbers":"LOD: 0.46 pM · detection range: 1.0–90.0 pM · sensitivity: 0.60 μA/pM · recovery in serum/urine: 96–104% · 3 cobalt nanostructure variants tested","methodology":"Lab-based sensor development study. Three cobalt-based carbon nanostructure variants were synthesized and functionalized with anti-exendin-4 antibodies. Sensor performance was evaluated using chronoamperometry (measuring current changes over time). The best sensor was validated against spiked human blood serum and urine samples.","limitations":"Tested only with spiked samples, not patient samples from people actually taking exendin-4. No head-to-head comparison with existing detection methods like ELISA or mass spectrometry. Long-term sensor stability, shelf life, and manufacturing scalability were not assessed. Real-world interference from other peptide drugs was not evaluated."},{"rthcId":"RPEP-14537","title":"Bioactive peptides with antioxidant and ACE inhibitory properties in goat milk protein hydrolysates: Peptidomics and molecular docking study.","authors":"Zhang, Wenhua; Abubaker, Mohamed Aamer; Li, Zekun; He, Yu; Shu, Qin; Li, Linqiang; Liu, Yongfeng","year":2025,"journal":"International journal of biological macromolecules, 299, 140286","doi":"10.1016/j.ijbiomac.2025.140286","pmid":"39863228","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14538","title":"DR8 (DHNNPQIR), a rapeseed-derived peptide, mitigates fibrosis and muscle atrophy in chronic kidney disease by targeting CNR1-ERK/ELK-1 signaling.","authors":"Zhang, Wenli; Zuo, Yidan; Xu, Diyan; Lin, Yibei; Zang, Yaoxue; Chen, Ruyi; Chen, Mingli; Su, Zhen","year":2025,"journal":"Peptides, 194, 171456","doi":"10.1016/j.peptides.2025.171456","pmid":"41338434","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14539","title":"A sonosensitive diphenylalanine-based broad-spectrum antimicrobial peptide.","authors":"Zhang, Xiaoguang; Feng, Xiaobo; Ma, Liang; Lei, Jie; Li, Gaocai; Zhang, Weifeng; Liang, Huaizhen; Tong, Bide; Wu, Di; Yang, Cao; Tan, Lei","year":2025,"journal":"Nature biomedical engineering, 9(8), 1349-1365","doi":"10.1038/s41551-025-01377-w","pmid":"40316686","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The peptide FFRKSKEK (derived from the human LL-37 host defense peptide) showed high broad-spectrum antibacterial efficiency (>99%) against five clinically isolated methicillin-resistant bacteria — S. aureus, E. coli, S. epidermidis, E. cancerogenus, and P. aeruginosa — with just 15 minutes of ultrasound irradiation.\n\nCritically, the peptide had negligible toxicity to mammalian cells and low self-antibacterial activity (meaning it only kills effectively when activated by ultrasound, providing a built-in safety mechanism). Molecular dynamics simulations revealed that ultrasound amplifies the peptide's membrane-penetrating ability through piezoelectric polarization of the diphenylalanine sequence, which also generates reactive oxygen species and disrupts bacterial electron transport chains. In a goat model of intervertebral infection — one of the most difficult infection sites to treat — the sonosensitive peptide produced better outcomes than vancomycin.","whyItMatters":"Antibiotic-resistant infections kill over 1.2 million people annually and the problem is worsening. Traditional antimicrobial peptides have shown promise but suffer from slow action, rapid degradation, and toxicity to healthy cells. This sonosensitive approach solves all three problems: the peptide acts within 15 minutes, is only active when triggered by ultrasound (minimizing off-target toxicity), and is just 8 amino acids long (cheaper and easier to manufacture than complex peptides). Outperforming vancomycin — the drug of last resort — in a large animal model is a remarkable achievement.","specificNumbers":"","methodology":"Researchers screened a library of peptides containing piezoelectric diphenylalanine (FF) sequences for optimal hydrophobicity, net positive charge, and low toxicity. The selected peptide (FFRKSKEK) was tested against five clinically isolated resistant bacteria with and without ultrasound. All-atom molecular dynamics simulations elucidated the mechanism of ultrasound-enhanced membrane penetration. A goat model of intervertebral disc infection was used for in vivo comparison against vancomycin. Published in Nature Biomedical Engineering.","limitations":"The goat infection model, while impressive, involved a specific type of deep bone/disc infection — performance against other infection types and sites was not tested. The requirement for ultrasound equipment limits use to clinical settings and makes this unsuitable for simple outpatient antibiotic use. Long-term in vivo toxicity data were not presented. The peptide's stability and pharmacokinetics in human tissue need to be established. Whether bacteria could develop resistance to this mechanical/oxidative killing mechanism over time is unknown."},{"rthcId":"RPEP-14540","title":"Immunization with the M12-N, M12-C, and M12-N+C fusion peptides derived from the M12 protein elicited varying levels of protective immune responses against multiple serotypes of group A Streptococcus.","authors":"Zhang, Xiaolan; Ma, Yue; Na, Rige; Hou, Wenli; Hanski, Emanuel; Zhou, Qin","year":2025,"journal":"Frontiers in immunology, 16, 1636591","doi":"10.3389/fimmu.2025.1636591","pmid":"41357204","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The M12-C peptide vaccine candidate showed multiple advantages: shortened vaccination schedule, enhanced antibody levels, and improved survival against both vaccine-type and non-vaccine-type streptococcal strains. M12-C antiserum demonstrated opsonization and killing of multiple non-vaccine strains (M1, M3, M6, M18). All three vaccine candidates induced Th1-type responses with IFN-γ secretion and increased effector memory T cells.","whyItMatters":"Group A Streptococcus causes millions of infections annually with no approved vaccine. A peptide-based approach that protects across multiple serotypes could finally enable a broadly effective GAS vaccine.","specificNumbers":"M12-N: 28.14 kDa; M12-C: 30.24 kDa; M12-N+C: 29.19 kDa; Cross-reactive against M1, M3, M6, M18 serotypes","methodology":"Three fusion peptide constructs (M12-N, M12-C, M12-N+C) derived from the M12 protein were expressed with a KSI tag and formulated with aluminum hydroxide adjuvant. Mice were immunized and evaluated for antibody titers, survival after subcutaneous challenge with homologous (MGAS9429) and heterologous (MGAS5005) strains, T cell responses, and opsonophagocytic killing of multiple GAS serotypes.","limitations":"Preclinical mouse study — human immune responses to M protein peptides may differ and carry autoimmune risks (rheumatic fever/heart disease). Cross-reactivity with human cardiac tissue was not assessed. Only a limited number of GAS serotypes were tested for cross-protection. Long-term safety data is lacking. The aluminum hydroxide adjuvant used may not be optimal for clinical development."},{"rthcId":"RPEP-14541","title":"The GLP-1 receptor agonist liraglutide inhibits necroptosis and neuroinflammation in a mouse model of Parkinson's disease with diabetes co-morbidity.","authors":"Zhang, Xiaomin; Du, Pengyang; Bai, Bo; Feng, Peng; Lian, Xia; Hölscher, Christian; Wang, Yongqing; Xue, Guofang","year":2025,"journal":"Frontiers in neuroscience, 19, 1596506","doi":"10.3389/fnins.2025.1596506","pmid":"40606832","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14542","title":"Predictive value of baseline serum sST2 and BNP levels for treatment efficacy in patients with heart failure.","authors":"Zhang, Xiaoming; Zhang, Shaosen","year":2025,"journal":"American journal of translational research, 17(6), 4484-4492","doi":"10.62347/KQWC4381","pmid":"40672628","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14543","title":"Probing Peptide Assembly and Interaction via High-Resolution Imaging Techniques: A Mini Review.","authors":"Zhang, Xiaoming; Yang, Zhanshu; Lin, Jiaxuan; Zhou, Wei; Sun, Nan; Jia, Yi","year":2025,"journal":"International journal of molecular sciences, 26(9)","doi":"10.3390/ijms26093998","pmid":"40362238","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14544","title":"Lung-directed delivery of a ligand-mediated chimeric lysin has an enhanced ability to eradicate pulmonary and intracellular Staphylococcus aureus.","authors":"Zhang, Xiaoxu; Xiong, Dongyan; Li, Xiaohong; Xue, Heng; Chen, Min; Yu, Junping; Wei, Hongping","year":2025,"journal":"BMC microbiology, 25(1), 262","doi":"10.1186/s12866-025-03978-6","pmid":"40312318","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14545","title":"Enhancing fat graft survival: thymosin beta-4 facilitates mitochondrial transfer from ADSCs via tunneling nanotubes by upregulating the Rac/F-actin pathway.","authors":"Zhang, Xiaoyu; Lin, Yan; Li, Haoran; Wang, Qian; Mu, Dali","year":2025,"journal":"Free radical biology & medicine, 228, 281-298","doi":"10.1016/j.freeradbiomed.2024.12.061","pmid":"39761767","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14546","title":"3D Printed Microsphere-Hydrogel Scaffold Facilitates Restoration of Reinnervation in Bone Regeneration through Programmable Release of NGF/BMP-2 Mimetic Peptides.","authors":"Zhang, Xin; Wang, Shuhan; Yang, Qianwen; Chen, Anbei; Dong, Shuao; Liao, Liqiong; Zhang, Chao","year":2025,"journal":"Advanced healthcare materials, 14(20), e2501594","doi":"10.1002/adhm.202501594","pmid":"40468637","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14547","title":"Sishun Formula for acute migraine attack: study protocol for a double-blind, randomized, placebo-controlled trial.","authors":"Zhang, Xuran; Liu, Jiaojiao; Li, Huanqin; Zhou, Bo; Wang, Shaoqing; Li, Lexi; Wu, Xuefeng; Cao, Kegang","year":2025,"journal":"Frontiers in neurology, 16, 1643130","doi":"10.3389/fneur.2025.1643130","pmid":"41281569","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14548","title":"A phase II randomized trial of individualized neoantigen peptide vaccine combined with unusual radiotherapy (iNATURE) in advanced solid tumors-GCOG0028.","authors":"Zhang, Yan; Hu, Ye-Fan; Ma, Lingyu; Wu, Yifei; Chao, Dandan; Chen, Xian; Xu, Zhiyuan; Su, Xiaoping; Dai, Wei; Huang, Jiandong; Fu, Pingfu; Kong, Feng-Ming Spring","year":2025,"journal":"Frontiers in immunology, 16, 1538032","doi":"10.3389/fimmu.2025.1538032","pmid":"40918097","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"This is a trial protocol rather than a results paper. The study introduces a novel combination of individualized neoantigen peptide vaccines with critical lesion radiotherapy (CLERT) for stage IV cancer patients across multiple tumor types.\n\nKey design features include a randomized 1:1 allocation with placebo control (rare in neoantigen trials), a crossover design allowing placebo patients to switch to the vaccine arm upon progression, and a basket-trial framework that leverages shared neoantigens across cancer types. The primary endpoints are progression-free survival and objective response rate.","whyItMatters":"Neoantigen vaccines are one of the most personalized cancer treatments possible — they're designed from each patient's own tumor mutations. But in advanced cancers, they haven't worked well alone because the immune system is too suppressed and tumor burden too high. This trial tests a promising solution: using targeted radiation to prime the immune system before vaccination, potentially making the vaccine far more effective in patients with few options left.","specificNumbers":"","methodology":"This is an open-label, multicenter Phase II randomized trial. Patients with advanced solid tumors (including melanoma, glioblastoma, lung cancer, and colorectal cancer) who have failed first-line therapy are randomized 1:1 to receive either personalized neoantigen peptide vaccine plus conventional treatment (with high and low dose radiotherapy) or placebo plus conventional treatment. A one-way crossover lets placebo patients switch to the vaccine arm if their disease progresses. Patients must have at least one predicted high-quality tumor neoantigen, an ECOG score of 0-2, and projected survival of at least 3 months.","limitations":"No results are available yet — this is a protocol description only. The open-label design means patients and doctors know who is receiving the vaccine, which could influence assessments. Manufacturing personalized vaccines requires tumor sequencing and neoantigen prediction, which may not be accessible outside major medical centers. The crossover design, while ethical, may complicate interpretation of overall survival data."},{"rthcId":"RPEP-14549","title":"Engineered Bacteria-Mediated Delivery of Scorpion Venom Peptide AGAP for Targeted Breast Cancer Therapy.","authors":"Zhang, Yang; Li, Xianglong; Tian, Chuanjun; Zhong, Chunyan; Li, Wenwen; Shang, Xiaobing; Zhao, Minghui; Zhao, Yongshan","year":2025,"journal":"Current microbiology, 82(7), 323","doi":"10.1007/s00284-025-04289-9","pmid":"40459583","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14550","title":"Intestinal TGR5-targeted carrier-drug conjugate improves glycemic control in mice and pigs.","authors":"Zhang, Yaqi; Huang, Hui; Wang, Yaying; Li, Xiang; Hou, Peizhou; Yu, Miaorong; Zhang, Zhuan; Guo, Shiyan; Liu, Chang; Zhang, Zilong; Zhuo, Yan; Zhu, Chunliu; Zhang, Pengcheng; Wang, Shisheng; Zhou, Hu; Gan, Yong","year":2025,"journal":"Science translational medicine, 17(825), eado5177","doi":"10.1126/scitranslmed.ado5177","pmid":"41259536","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14551","title":"The Novel Dual GIP and GLP-1 Receptor Agonist Tirzepatide Attenuates Colon Cancer Development by Regulating Glucose Metabolism.","authors":"Zhang, Yikai; Xie, Yi; Xia, Shenglong; Ge, Xinnuo; Li, Jiaying; Liu, Fang; Jia, Fan; Wang, Shengyao; Zhou, Qiao; Gao, Menghan; Fang, Weihuan; Zheng, Chao","year":2025,"journal":"Advanced science (Weinheim, Baden-Wurttemberg, Germany), 12(19), e2411980","doi":"10.1002/advs.202411980","pmid":"40125821","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14552","title":"Effect of liraglutide on the dysglycemia, inflammation, and gut microbiota in prediabetic KKay mice.","authors":"Zhang, Ying; Yang, Xiaoxiao; Yang, Ping; Sun, Huihuan; Chen, Lijuan; Zhang, Xiaojun; Liu, Shudong","year":2025,"journal":"Frontiers in pharmacology, 16, 1714859","doi":"10.3389/fphar.2025.1714859","pmid":"41394123","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14553","title":"Tear neuropeptides are associated with clinical symptoms and signs of dry eye patients.","authors":"Zhang, Yirou; Zhang, Hong; Zhu, Xingyu; Ye, Han; Yang, Kan; Zhou, Xujiao; Hong, Jiaxu","year":2025,"journal":"Annals of medicine, 57(1), 2451194","doi":"10.1080/07853890.2025.2451194","pmid":"39823189","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14554","title":"Electroacupuncture at ST36 ameliorates gastric dysmotility in rats with diabetic gastroparesis via the nucleus tractus solitarius-vagal axis.","authors":"Zhang, You; Tang, Yi-Wen; Zhou, Jin; Wei, Yan-Rong; Peng, Yu-Ting; Yan, Zi; Yue, Zeng-Hui","year":2025,"journal":"World journal of gastroenterology, 31(21), 107395","doi":"10.3748/wjg.v31.i21.107395","pmid":"40538511","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Electroacupuncture at ST36 significantly increased gastric emptying rate, restored stomach slow-wave rhythms, and improved smooth muscle architecture in diabetic gastroparesis rats. The treatment reduced inflammatory infiltration and increased expression of nNOS, C-kit, and SCF — markers of healthy stomach nerve and muscle function.\n\nThe mechanism was mapped to a specific neural circuit: electroacupuncture activated vagal targets (ChAT and α7nAChR) at the stimulation site, sending signals through spinal segments L4-L6 to the nucleus tractus solitarius (NTS) in the brainstem, which then regulated gastrointestinal peptides (gastrin, motilin, and vasoactive intestinal peptide) and restored interstitial cells of Cajal function via vagal efferent pathways.\n\nCritically, subdiaphragmatic vagotomy completely abolished the electroacupuncture-induced improvements in gastric motility and ICC recovery, confirming the vagus nerve is indispensable to this therapeutic effect.","whyItMatters":"Diabetic gastroparesis affects a significant proportion of diabetes patients and has limited treatment options. This study provides a detailed molecular map of how electroacupuncture may improve stomach function, moving acupuncture research from observational claims to mechanistic understanding. The identification of specific peptide targets (gastrin, motilin, VIP) in this pathway could inform future drug development.","specificNumbers":"","methodology":"Researchers induced diabetic gastroparesis in rats using a single high-dose injection of streptozotocin combined with 8 weeks of a high-sugar, high-fat diet. They then compared electroacupuncture at ST36 against pharmacological interventions (ChAT agonist and inhibitor) and subdiaphragmatic vagotomy. Outcomes were assessed using phenol red gastric emptying assays, slow-wave recordings, PET-CT imaging, histopathological analysis, Western blot, immunofluorescence, and ELISA for gastrointestinal peptides.","limitations":"This was an animal study in rats, so the results may not directly translate to humans. The diabetic gastroparesis model was chemically induced, which may not fully replicate the gradual nerve damage seen in human diabetes. The study does not report specific sample sizes per group in the abstract, and no behavioral or quality-of-life outcomes were measured. Long-term effects of the treatment were not assessed."},{"rthcId":"RPEP-14555","title":"Application of nimodipine combined with statins in the treatment of subarachnoid haemorrhage.","authors":"Zhang, Yu; Ma, Feifan; Gan, Ning; Xu, Zhijie; Jiao, Yang; Zhang, Jiancang","year":2025,"journal":"JPMA. The Journal of the Pakistan Medical Association, 75(5), 767-771","doi":"10.47391/JPMA.11366","pmid":"40500822","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Combination therapy (nimodipine + statins) achieved 90% overall response rate versus 68% with nimodipine alone (p<0.05). After 7 days, the combination group had significantly lower endothelin-1 levels, higher CGRP levels, lower VEGF levels, higher peroxiredoxin 2 levels, and slower mean cerebral artery blood flow velocity (indicating less vasospasm). Adverse reactions occurred in only 6% of the combination group versus 20% with nimodipine alone (p<0.05).","whyItMatters":"Subarachnoid hemorrhage is a devastating form of stroke with high mortality. Vasospasm — dangerous brain blood vessel constriction driven by the balance between vasoconstricting peptides (endothelin-1) and vasodilating peptides (CGRP) — is a leading cause of secondary brain damage. This study shows that adding statins to nimodipine improves this critical peptide balance, directly connecting peptide biomarker changes to better patient outcomes.","specificNumbers":"","methodology":"Retrospective study of 100 subarachnoid hemorrhage patients at Baoding No.1 Central Hospital, China (March 2019-2022). Group A (n=50) received nimodipine alone; Group B (n=50) received nimodipine plus statins. Endothelin-1, CGRP, VEGF, and peroxiredoxin 2 were measured at baseline and day 7. Mean cerebral artery blood flow velocity and adverse reactions were compared. Analysis used SPSS 22.","limitations":"This is a retrospective, non-randomized study from a single Chinese hospital, introducing selection bias and limiting generalizability. The sample size of 100 is relatively small for a clinical study. Specific statin type and dose weren't detailed in the abstract. The 7-day follow-up is short, and long-term outcomes weren't reported. The study lacks blinding, which could influence outcome assessment."},{"rthcId":"RPEP-14556","title":"Cancer cells co-opt an inter-organ neuroimmune circuit to escape immune surveillance.","authors":"Zhang, Yu; Guo, Yibo; Liu, Zheqi; Sun, Yiting; Yang, Xi; Chen, Mingtao; Feng, Guanying; Lin, Chengzhong; Wang, Yang; Zhang, Zhen; Zhu, Yun; Ye, Jinhai; Liu, Jiajia; Shi, Jun; Zhou, Xiaomeng; Han, Qingjian; Liu, Yu; Jiang, Qian; Yu, Youcheng; Wang, Xu; Zhang, Chenping; Sun, Yunfan; Zhou, Jian; Fan, Jia; Ji, Tong","year":2025,"journal":"Cell, 188(24), 6754-6773.e29","doi":"10.1016/j.cell.2025.09.029","pmid":"41138728","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14557","title":"Milk peptides alleviate irritable bowel syndrome by suppressing colonic mast cell activation and prostaglandin E2 production in mice.","authors":"Zhang, Yu; Lin, Zhiqing; Yao, Qi; He, Jian; Feng, Haotian; Zhang, Wenyi; Liu, Zhigang; Yuan, Tian; Liu, Xuebo; Ding, Long","year":2025,"journal":"Food research international (Ottawa, Ont.), 211, 116470","doi":"10.1016/j.foodres.2025.116470","pmid":"40356133","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Casein and whey hydrolysates reduced IBS symptoms (diarrhea, anxiety, visceral hypersensitivity), improved gut barrier proteins (ZO-1, claudin-1, occludin), decreased pro-inflammatory cytokines (IL-6, IL-1β, TNF-α), increased IL-10, reduced mast cell activation and PGE2 production, and reshaped gut microbiota. Three novel COX2-inhibitory peptides identified: RGPF (IC50 0.36 mM), FPK (IC50 0.64 mM), NPW (IC50 1.10 mM).","whyItMatters":"IBS affects 10-15% of the global population with limited treatment options. Finding that common milk-derived peptides address multiple IBS mechanisms — inflammation, mast cell activation, gut barrier, and microbiome — suggests a safe, food-based therapeutic approach.","specificNumbers":"1 g/kg/day for 24 days; RGPF IC50 0.36 mM; FPK IC50 0.64 mM; NPW IC50 1.10 mM; Increased Alloprevotella and Alistipes","methodology":"Mice received casein or whey hydrolysates orally for 24 days during IBS induction (C. rodentium infection + water avoidance stress). Outcomes: stool consistency, anxiety behavior, visceral sensitivity, gut microbiota (16S sequencing), tight junction proteins (RT-qPCR), cytokines, mast cell activation, PGE2 levels. Novel peptides identified by LC-MS/MS and validated for COX2 inhibition with molecular docking.","limitations":"Mouse IBS model may not fully represent human IBS pathophysiology. The hydrolysates are complex mixtures — individual peptide contributions unclear. COX2 inhibition IC50 values are in mM range (relatively high). No human clinical data. Short treatment duration (24 days). Specific hydrolysate composition not standardized for reproducibility."},{"rthcId":"RPEP-14558","title":"Association of Glucagon-like peptide-1 receptor agonists use with fracture risk in type 2 diabetes: A meta-analysis of randomized controlled trials.","authors":"Zhang, Yuan; Chen, Guanhua; Wang, Weimin; Yang, Donghui; Zhu, Dalong; Jing, Yali","year":2025,"journal":"Bone, 192, 117338","doi":"10.1016/j.bone.2024.117338","pmid":"39603373","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14559","title":"Semaglutide treatment for type 2 diabetes in a patient with chronic myeloid leukemia: A case report and review of the literature.","authors":"Zhang, Yuchen; Li, Anxin","year":2025,"journal":"Open medicine (Warsaw, Poland), 20(1), 20251184","doi":"10.1515/med-2025-1184","pmid":"40292250","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14560","title":"pH-Responsive Hyperbranched Polymer Scaffolds for Polymer and Peptide Conjugation through Molecular Recognition: Synthesis and Self-Assembly.","authors":"Zhang, Yue; Tian, Liyuan; Zhang, Jimin; Zhong, Meihui","year":2025,"journal":"Biomacromolecules, 26(5), 2960-2970","doi":"10.1021/acs.biomac.5c00041","pmid":"40234736","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14561","title":"Scorpion venom heat-resistant synthetic peptide improves cognitive dysfunction of APP/PS1 mice through microglial retromer complex.","authors":"Zhang, Yue; Wu, Yu-Xia; Zhang, Xiao-Gang; Guo, Song-Yu; He, Jia; Hu, Na-Na; Huang, Yue-Lin; Kong, Yue; Li, Qi-Fa; Sui, Ao-Ran; Zhu, Bao-Hang; Piao, Hua; Zhao, Jie; Li, Shao","year":2025,"journal":"British journal of pharmacology, 182(21), 5391-5408","doi":"10.1111/bph.70124","pmid":"40660634","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14562","title":"Oral Delivery of Semaglutide and Tirzepatide Using Milk-Derived Small Extracellular Vesicles.","authors":"Zhang, Yuefei; Han, Jianyi; Wu, Wei; Dang, Bobo","year":2025,"journal":"Journal of extracellular biology, 4(11), e70099","doi":"10.1002/jex2.70099","pmid":"41293773","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14563","title":"Ex vivo lung perfusion with GLP-1R agonist mitigates ischemia/reperfusion injury through pyroptosis modulation in lung transplantation- an experimental study.","authors":"Zhang, Yufei; Liu, Tao; Guo, Huaizu; Shi, Jianxin; Yang, Jun; Fu, Shijie; Pan, Xufeng; Li, Feng; Zhang, Hai; Zhang, Dawei; Yang, Hong; Zheng, Lulu; Shi, Meng; Zhou, Wenyong","year":2025,"journal":"International journal of surgery (London, England), 111(6), 3781-3797","doi":"10.1097/JS9.0000000000002438","pmid":"40387728","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14564","title":"Effects of Central Administration of Opioid Peptides, Vasotocin, Mesotocin, and Corticotrophin-Releasing Factor on Water Intake in Chicks.","authors":"Zhang, Yuhui; Murata, Kaoruko; Takegaki, Junya; Saneyasu, Takaoki; Honda, Kazuhisa","year":2025,"journal":"The journal of poultry science, 62, 2025011","doi":"10.2141/jpsa.2025011","pmid":"40060327","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14565","title":"Chronic intermittent hypoxia exacerbates isoproterenol-induced cardiac hypertrophy and apoptosis.","authors":"Zhang, Yujie; Zhang, Ming; Jiang, Hongfeng; Fang, Fang","year":2025,"journal":"Frontiers in cardiovascular medicine, 12, 1700967","doi":"10.3389/fcvm.2025.1700967","pmid":"41567385","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14566","title":"Clinical efficacy of GLP-1 receptor agonists in the treatment of Parkinson's disease: a systematic review and meta-analysis of randomized controlled trials.","authors":"Zhang, Yujing; Wang, Cong; Wang, Yuqing; Wang, Tianjun","year":2025,"journal":"Journal of neurology, 272(9), 555","doi":"10.1007/s00415-025-13301-y","pmid":"40760123","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14567","title":"Serum interleukin-6, tumour necrosis factor-a, D-dimer after recombinant human brain natriuretic peptide combined with levosimendan in patients with heart failure.","authors":"Zhang, Yujing; Fei, Pingyan; Liu, Xinyu","year":2025,"journal":"Journal of medical biochemistry, 44(5), 1100-1109","doi":"10.5937/jomb0-56202","pmid":"40951892","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14568","title":"Activation of AMPK by GLP-1R agonists mitigates Alzheimer-related phenotypes in transgenic mice.","authors":"Zhang, Yun; Chen, Huaqiu; Feng, Yijia; Liu, Mingjing; Lu, Zhi; Hu, Bolang; Chen, Lifen; Zhang, Yang; Liu, Jiawen; Cai, Fang; Zhao, Yifan; Pan, Wenhao; Liao, Xinxin; Pan, Sipei; Bestard-Lorigados, Isabel; Wu, Yili; Song, Weihong","year":2025,"journal":"Nature aging, 5(6), 1097-1113","doi":"10.1038/s43587-025-00869-3","pmid":"40394225","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 receptor agonists activated CaMKK2-AMPK signaling in the brain, which reduced BACE1-mediated cleavage of amyloid precursor protein and lowered amyloid-beta generation. Plasma GLP-1 levels were found to be decreased in Alzheimer's model mice and negatively correlated with amyloid-beta load in human patients with AD.\n\nIn microglia (the brain's immune cells), GLP-1RAs increased AMPK activity, which inhibited neuroinflammation and promoted the clearance of amyloid-beta through phagocytosis. The combined effects led to reduced amyloid plaque formation and improved memory deficits in transgenic Alzheimer's mice.","whyItMatters":"Alzheimer's disease currently has very limited treatment options. The discovery that widely available GLP-1 diabetes medications work through a specific molecular pathway (AMPK) to reduce multiple Alzheimer's hallmarks — amyloid plaques, neuroinflammation, and memory loss — provides a clear mechanistic rationale for repurposing these peptide drugs for neurodegenerative disease, potentially accelerating clinical trials.","specificNumbers":"","methodology":"Researchers used transgenic mice engineered to develop Alzheimer's-like pathology. They measured plasma GLP-1 levels in these mice and correlated amyloid-beta load with GLP-1 levels in human AD patients. The mice were treated with GLP-1 receptor agonists and assessed for changes in AMPK signaling, amyloid-beta production, neuroinflammation markers in microglia, plaque formation, and memory performance through behavioral tests.","limitations":"This was an animal study using transgenic mouse models, which do not fully replicate human Alzheimer's disease. The correlation between GLP-1 levels and amyloid-beta in human patients is observational and does not prove causation. The study did not test specific dosing regimens that would translate to human use, and the long-term effects of GLP-1RA treatment on brain pathology remain unknown. Results from mouse models frequently do not translate to human clinical outcomes."},{"rthcId":"RPEP-14569","title":"BDNF Regulation of Myocardial Infarction.","authors":"Zhang, Yuping; Liu, Shuke; Yang, Shiyu; Yao, Yisong; Zhao, Chunjiao; Pei, Zhenying; Zhang, Shanwen","year":2025,"journal":"International heart journal, 66(5), 763-770","doi":"10.1536/ihj.24-748","pmid":"41034021","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14570","title":"Recombinant human thymosin beta 4 improves ischemic cardiac dysfunction in mice and patients with acute ST-segment elevation myocardial infarction after reperfusion.","authors":"Zhang, Yuze; Dong, Qiuting; Bian, Xiaohui; Qiao, Zheng; Cui, Chuanjue; Yang, Ning; Liu, Jincan; Fu, Rui; Zhang, Jun; Jia, Lei; Wu, Chao; Guo, Jincheng; Lin, Wenhua; Wang, Jingping; Fan, Jiamao; Li, Yang; Liu, Fan; Yang, Bin; Jia, Xinwei; Gao, Chuanyu; Bai, Ming; He, Yi; Han, Chengquan; Yin, Dong; Dou, Kefei","year":2025,"journal":"Cardiovascular research, 121(17), 2747-2758","doi":"10.1093/cvr/cvaf223","pmid":"41229390","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14571","title":"Effect of Hypoglycemic Drugs on Patients with Heart Failure with or without T2DM: A Bayesian Network Meta-analysis.","authors":"Zhang, Zhaolun; Liu, Siqi; Xian, Jiawen; Zhang, Yali; Zhang, Chunyu; Wang, Zhiyuan; Deng, Hongmei; Feng, Jian; Yao, Lei","year":2025,"journal":"Reviews in cardiovascular medicine, 26(3), 26154","doi":"10.31083/RCM26154","pmid":"40160590","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14572","title":"Ddx21 mutant peptide is an effective neoantigen in prophylactic lung cancer vaccines and activates long-term anti-tumor immunity.","authors":"Zhang, Zhe; Xia, Yimeng; Wang, Zhihong; Sun, Yaxing; Pu, Dan; He, Yijia; Liu, Ruixian; Zhang, Yanru; Liu, Yan; Yu, Junzhi; Ning, Shiyang; Feng, Baisui; Wang, Yaohe; Wang, Na","year":2025,"journal":"Frontiers in immunology, 16, 1500417","doi":"10.3389/fimmu.2025.1500417","pmid":"39981234","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14573","title":"Self-assembling peptide hydrogels: design, mechanisms, characterization, and biomedical applications.","authors":"Zhang, Zhenhong; Gao, Jinhong; Yuan, Libo; Duan, Bingchao; Yang, Hongyan; Ma, Li; Lu, Kui","year":2025,"journal":"Soft matter, 21(24), 4771-4791","doi":"10.1039/d5sm00396b","pmid":"40452332","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14574","title":"Tirzepatide safety in type 2 diabetes: a disproportionality analysis of adverse events using the FDA FAERS database.","authors":"Zhang, Zhenpo; Li, Jiangxiong; Zheng, Jingping; Liang, Yankun; Ma, Lin; Su, Ling","year":2025,"journal":"Endocrine connections, 14(7)","doi":"10.1530/EC-25-0205","pmid":"40631601","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14575","title":"Protease Stabilizing Antimicrobial Peptide D1018M Showed Potent Antibiofilm and Anti-Intracellular Bacteria Activity Against MRSA.","authors":"Zhang, Zirui; Jiao, Jian; Zhang, Jili; Tan, Lian; Dong, Xunxi; Wu, Runzhe; Wang, Qiang; Wang, Hao; Wang, Xiao","year":2025,"journal":"Foodborne pathogens and disease","doi":"10.1089/fpd.2024.0134","pmid":"40229950","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14576","title":"Exploring the healthy potential of goat milk fermented by novel isolated lactic acid bacteria: Genetic identification, bioactive peptides, nutritional mechanism and sensory evaluation.","authors":"Zhang, Zongcai; Shu, Guowei; Nan, Jianhao; Meng, Fanbo; Zhang, Meng; Chen, Li","year":2025,"journal":"International journal of food microbiology, 442, 111354","doi":"10.1016/j.ijfoodmicro.2025.111354","pmid":"40684662","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14577","title":"Mechanism analysis of the differences in relieving constipation in a Balb/c constipation model mouse fed human milk probiotics or fermented milk.","authors":"Zhao, Baoyuan; Wang, Yajuan; Wang, Shengyuan; Mu, Guangqing; Wu, Xiaomeng","year":2025,"journal":"Journal of the science of food and agriculture, 105(4), 2594-2606","doi":"10.1002/jsfa.14032","pmid":"39563650","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14578","title":"Transcriptome Analysis of Cabbage Near-Isogenic Lines Reveals the Involvement of the Plant Defensin Gene PDF1.2 in Fusarium Wilt Resistance.","authors":"Zhao, Cunbao; Liu, Xing; Zhou, Ailing; Ji, Jialei; Wang, Yong; Zhuang, Mu; Zhang, Yangyong; Yang, Limei; Ma, Lisong; Chellappan, Biju V; Artemyeva, Anna M; Lv, Honghao","year":2025,"journal":"International journal of molecular sciences, 26(8)","doi":"10.3390/ijms26083770","pmid":"40332410","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14579","title":"Beyond first-day biomarkers: The critical role of peak cardiac troponin I in sepsis prognosis.","authors":"Zhao, Dandan; Li, Huimin; Lin, Yongdi; Liu, Lizhen; Xu, Lina; Zhang, Dan; Fu, Yu; Hong, Jiang; Miao, Congliang","year":2025,"journal":"Heart & lung : the journal of critical care, 71, 14-19","doi":"10.1016/j.hrtlng.2025.01.013","pmid":"39914177","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14580","title":"Effects of Liraglutide on Leptin Promoter Methylation in Ovarian Granulosa Cells of Patients with Polycystic Ovary Syndrome and Obesity.","authors":"Zhao, Hongli; Guo, Yanying","year":2025,"journal":"Gynecologic and obstetric investigation, 90(1), 6-17","doi":"10.1159/000539039","pmid":"38768579","tags":[],"studyType":"retrospective-cohort","evidenceStrength":"low-moderate","keyFinding":"Liraglutide (a GLP-1 receptor agonist) outperformed metformin across multiple endpoints in women with PCOS and obesity. Compared to metformin, liraglutide produced greater improvements in glucose metabolism, lipid metabolism, BMI, leptin levels, and reproductive hormone levels (FSH, E2, LH) — all statistically significant (p<0.05).\n\nCritically, liraglutide reduced methylation of the leptin promoter in ovarian granulosa cells more than metformin. The liraglutide group also had higher rates of menstrual cycle restoration, normal ovulation, and natural pregnancy compared to the metformin group.","whyItMatters":"PCOS is the most common cause of infertility in women, and obesity worsens it. This study suggests liraglutide may improve fertility outcomes through an epigenetic mechanism — changing how the leptin gene is expressed in ovarian cells — offering a new angle on why GLP-1 drugs might help women with PCOS conceive naturally.","specificNumbers":"n=30 · 15 per group · p<0.05 for all comparisons · Liraglutide group had higher ovulation and pregnancy rates vs metformin","methodology":"Retrospective analysis of 30 women with PCOS and obesity, randomly divided into two groups of 15. The control group received metformin; the observation group received subcutaneous liraglutide injections. Researchers compared glucose/lipid metabolism markers, BMI, hormones (FSH, E2, LH), leptin promoter methylation in ovarian granulosa cells, and reproductive outcomes (menstrual regularity, ovulation, natural pregnancy).","limitations":"Very small sample size (15 per group) severely limits statistical power and generalizability. The study is described as retrospective yet uses random grouping, which is methodologically unclear. No specific dosing or duration details are provided in the abstract. The mechanism linking leptin promoter methylation to fertility outcomes is proposed but not conclusively demonstrated."},{"rthcId":"RPEP-14581","title":"Comparison of RECIST 1.1, mRECIST and PERCIST for assessment of peptide receptor radionuclide therapy treatment response in metastatic neuroendocrine tumors.","authors":"Zhao, Jack; Bera, Kaustav; Mohamed, Amr; Li, Qiubai; Ramaiya, Nikhil; Tirumani, Sree Harsha","year":2025,"journal":"Current problems in diagnostic radiology, 54(2), 228-232","doi":"10.1067/j.cpradiol.2024.10.003","pmid":"39389807","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14582","title":"Diversity Scale of Library Matters: Impact of mRNA Library Diversity Scales on the Discovery of Macrocyclic Peptides Targeting a Protein by the RaPID System.","authors":"Zhao, Jinxuan; Li, Yi; Terasaka, Naohiro; Aikawa, Haruo; Suga, Hiroaki","year":2025,"journal":"ACS central science, 11(3), 431-440","doi":"10.1021/acscentsci.4c01021","pmid":"40161957","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14583","title":"Effect of atrial fibrosis on clot burden score and physicochemical properties of thrombus in patients with ischaemic stroke occurring in non-valvular atrial fibrillation.","authors":"Zhao, Juan; Deng, Guangjun; Wang, Weijing; Wang, Peng; Shen, Xinyu; Yuan, Xiaoxiao; Jiang, Haifei; Ruan, Zhong-Bao","year":2025,"journal":"PeerJ, 13, e19173","doi":"10.7717/peerj.19173","pmid":"40151456","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14584","title":"Peripheral blood mesenchymal stem cell-derived exosomes improve renal sympathetic denervation efficacy through β-catenin-mediated cardiac reprogramming.","authors":"Zhao, Lan; Li, Chen; Huang, Zhichuan; Wang, Jianshuo; Deng, Zhanyu; Deng, Yanwen; Wang, Pengzhen; Zhang, Shaoheng","year":2025,"journal":"Clinical and translational medicine, 15(9), e70475","doi":"10.1002/ctm2.70475","pmid":"40910352","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14585","title":"Association of tirzepatide with cardiometabolic benefits in Chinese adults: post hoc subgroup analysis of SURMOUNT-CN study.","authors":"Zhao, Lin; Chen, Hong; Cheng, Zhifeng; Jiang, Hongwei; Lu, Yibing; Xiao, Jianzhong; Xiao, Xinhua; Li, Yuanyuan; Yuan, Yuan; Li, Xiaoying","year":2025,"journal":"Obesity (Silver Spring, Md.), 33(7), 1287-1296","doi":"10.1002/oby.24306","pmid":"40437798","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14586","title":"Predicting 10-year risk of type 2 diabetes in Chinese people with overweight or obesity treated with Tirzepatide: Post hoc analysis of SURMOUNT-CN trial.","authors":"Zhao, Lin; Tao, Feng; Cheng, Zhifeng; Lu, Yibing; Liu, Ming; Chen, Hong; Zhang, Min; Yang, Yang; Song, Xiang; Sun, Yuzi; Ma, Xiao; Si, Si; Zhang, Hanxi; Li, Xiaoying","year":2025,"journal":"Diabetes, obesity & metabolism, 27(8), 4118-4125","doi":"10.1111/dom.16439","pmid":"40329666","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In the SURMOUNT-CN trial post hoc analysis (n=169), tirzepatide 10 mg reduced predicted 10-year T2D risk from 5.3% to 1.2%, and 15 mg from 4.9% to 1.0%, compared to placebo (5.8% to 4.5%) at week 52. The LS mean risk reductions versus placebo were -3.2% (95% CI: -4.2% to -2.2%) for 10 mg and -3.4% (95% CI: -4.4% to -2.4%) for 15 mg. Significantly greater reductions were observed across all subgroups regardless of baseline BMI status or prediabetes status.","whyItMatters":"Diabetes prevention is a major public health goal, especially in Asian populations where diabetes risk increases at lower BMI thresholds. This analysis demonstrates that tirzepatide doesn't just help with weight loss — it fundamentally alters the metabolic trajectory, reducing predicted diabetes risk by approximately 75-80%. This supports the case for using GIP/GLP-1 dual agonists as diabetes prevention tools.","specificNumbers":"","methodology":"This was a post hoc analysis of the SURMOUNT-CN randomized controlled trial. Researchers used the QDiabetes-2018 risk engine to calculate predicted 10-year T2D risk at baseline, week 24, and week 52 for participants randomized to tirzepatide 10 mg (n=59), 15 mg (n=53), or placebo (n=57). A mixed model for repeated measures compared risk changes between groups, with subgroup analyses by BMI and prediabetes status.","limitations":"This is a post hoc analysis, not a pre-specified endpoint of the trial. The predicted T2D risk was calculated using a risk engine (QDiabetes-2018) rather than measuring actual diabetes incidence. The sample size is small (169 participants total). The 52-week timeframe does not capture what happens after medication is stopped. The QDiabetes tool was developed for a UK population and may not be perfectly calibrated for Chinese populations."},{"rthcId":"RPEP-14587","title":"Clinical efficacy and hemodynamic effects of levosimendan in cardiac surgery patients after surgery.","authors":"Zhao, Meiling; Hou, Yunfeng; Yuan, Meng; Ma, Shuang; Yue, Yifeng","year":2025,"journal":"Journal of cardiothoracic surgery, 20(1), 43","doi":"10.1186/s13019-024-03316-3","pmid":"39773754","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14588","title":"Burn scar pain: from mechanisms to treatments.","authors":"Zhao, Minjuan","year":2025,"journal":"Frontiers in physiology, 16, 1627798","doi":"10.3389/fphys.2025.1627798","pmid":"41070147","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14589","title":"Association between various dosage forms of semaglutide and ocular adverse events in a real-world setting.","authors":"Zhao, Tao; Zheng, Liting; Feng, Yiyun; Lao, Min; Huang, Yongmei; Wu, Guosong","year":2025,"journal":"BMC ophthalmology, 25(1), 248","doi":"10.1186/s12886-025-04096-7","pmid":"40289093","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14590","title":"Computer-aided drug design of SP94 peptide-functionalized human H-chain ferritin for targeted doxorubicin delivery.","authors":"Zhao, Weixiang; Huang, Feiyan; Uddin, Shahab; Zhao, Qian-Wen; Zhao, Jiahuan; Ding, Shuai Wen; Li, Zhongqin; Wang, Xin; Li, Yang; Li, Hongyu","year":2025,"journal":"International journal of biological macromolecules, 332(Pt 1), 148521","doi":"10.1016/j.ijbiomac.2025.148521","pmid":"41138863","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14591","title":"A novel generative framework for designing pathogen-targeted antimicrobial peptides with programmable physicochemical properties.","authors":"Zhao, Weizhong; Hou, Kaijieyi; Tang, Chang; Shen, Yiting; Liu, Jinlin; Hu, Xiaohua","year":2025,"journal":"PLoS computational biology, 21(12), e1013833","doi":"10.1371/journal.pcbi.1013833","pmid":"41460918","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The generative framework outperformed most existing computational models for designing antimicrobial peptides with specific activity against target bacteria. Key components and results:\n\n- A conditional Variational Autoencoder (cVAE) was pretrained to generate AMPs with editable physicochemical properties (charge, hydrophobicity, etc.)\n- A conditional diffusion model learned hidden representations of AMPs for targeting specific pathogens\n- MIC (minimum inhibitory concentration) predictors were built for specific bacterial strains\n- Systematic screening identified two 'star' AMP candidates for E. coli and two for S. aureus, each showing excellent antibacterial activity, low hemolysis, and favorable toxicity profiles\n- The framework allows 'programmable' peptide design — specifying desired properties and target pathogen as inputs","whyItMatters":"Traditional antimicrobial peptide discovery is slow — screening natural sources or random libraries for active compounds takes years. This AI framework flips the process: specify which bacterium you want to kill and what properties the peptide should have, and the system generates candidates automatically. As antibiotic resistance accelerates, the ability to rapidly design pathogen-specific peptide antibiotics could be transformative for medicine.","specificNumbers":"","methodology":"The researchers developed a two-stage generative AI framework. Stage 1: a conditional Variational Autoencoder was pretrained on known AMP sequences to generate new peptides with controllable physicochemical properties. Stage 2: a conditional diffusion model learned the relationship between peptide sequence features and activity against specific pathogens, with MIC predictors trained for E. coli and S. aureus. Generated peptides were screened computationally for antimicrobial efficacy, hemolytic activity, and toxicity. Performance was benchmarked against existing generative models.","limitations":"The identified 'star' AMPs were evaluated computationally — no wet-lab synthesis or experimental validation against actual bacteria was described in the abstract. Computational predictions of antimicrobial activity, hemolysis, and toxicity may not perfectly match experimental results. The framework was demonstrated against only two bacterial species (E. coli and S. aureus); performance against other pathogens including drug-resistant strains is unknown. The training data quality and diversity limit the chemical space the model can explore."},{"rthcId":"RPEP-14592","title":"Growth hormone-releasing peptide 6 (GHRP-6) hydrogel for acute kidney injury therapy via metabolic regulation.","authors":"Zhao, Xiaotong; Pan, Kai; Li, Rui; Liu, Meina; Li, Duo; Jia, Pingping; Han, Zhibo; Han, Zhong-Chao; Guo, Zhikun; Li, Zongjin; Li, Qiong","year":2025,"journal":"Journal of nanobiotechnology, 24(1), 15","doi":"10.1186/s12951-025-03888-9","pmid":"41327290","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14593","title":"Cell Wall-Binding Proteins-Armed Controlled-Release Nanodelivery System Enhances Nisin's Efficacy against Streptococcus pneumoniae Infections.","authors":"Zhao, Xinghong; Liu, Jinhuan; Fan, Xin; Zhong, Xinyi; Wang, Yijue; Yang, Shinong; Tan, Huirong; Deng, Jiarong; Song, Xu; Xie, Shuyu; Jia, Renyong; Yin, Zhongqiong; Wan, Hongping","year":2025,"journal":"ACS nano, 19(40), 35370-35384","doi":"10.1021/acsnano.5c01115","pmid":"41045451","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14594","title":"Angiotensin-Converting Enzyme Inhibitory Peptide Derived from Ultrafine Lycium barbarum Pomace Powder: In Vitro and In Silico Analysis.","authors":"Zhao, Yuxin; Cui, Huimin; Lin, Hong; Gong, Wei; Li, Na; Yang, Jianjun","year":2025,"journal":"Journal of agricultural and food chemistry, 73(32), 20149-20162","doi":"10.1021/acs.jafc.5c01994","pmid":"40738476","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14595","title":"Comparison of GLP-1 Receptor Agonists Combined with Metformin Versus Metformin Alone in the Management of PCOS: A Comprehensive Meta-Analysis.","authors":"Zhao, Yuzi; Jiang, Li; Li, Na; Cao, Jing; Pi, Jie","year":2025,"journal":"Reproductive sciences (Thousand Oaks, Calif.), 32(5), 1661-1675","doi":"10.1007/s43032-025-01788-9","pmid":"39881036","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14596","title":"An optimized integrin α6-targeted peptide capable of delivering toxins for melanoma treatment.","authors":"Zhao, Zheng; Li, Zi-Qian; Huang, Ying-Bin; Liu, Meng-Meng; Cao, Fei; Bu, Guo-Long; Xu, Peng-Fei; Fang, Qi; Hu, Zhu-Long; Wu, Di; Feng, Guo-Kai; Liu, Xue-Kui","year":2025,"journal":"Journal of translational medicine, 23(1), 495","doi":"10.1186/s12967-025-06511-5","pmid":"40307853","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14597","title":"Food-specific IgG-based elimination diet decreased IL-6, TNF-α, and CGRP and improved symptoms in adults with migraine.","authors":"Zhao, Zhiming; Yang, Meimei; Wan, Fujun; Ning, Baoli; Song, Tao; Fu, Jun; Zhang, Liming","year":2025,"journal":"Frontiers in nutrition, 12, 1720389","doi":"10.3389/fnut.2025.1720389","pmid":"41473187","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14598","title":"A brief discussion on the role of calcitonin gene-related peptide in the efficacy of rehabilitation medicine.","authors":"Zhencheng, Guan; Aiguo, Xue","year":2025,"journal":"Frontiers in rehabilitation sciences, 6, 1593487","doi":"10.3389/fresc.2025.1593487","pmid":"40551895","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14599","title":"Proteomic Profiling of GLP-1-Mediated Cardioprotection in a Large Animal Model of Chronic Coronary Artery Disease.","authors":"Zheng, Clark; Stone, Christopher; Muir, Kelsey; Harris, Dwight; Sellke, Frank W","year":2025,"journal":"Medical research archives, 13(11)","doi":"10.18103/mra.v13i11.7114","pmid":"41717240","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14600","title":"Smart Dual-Targeted NRP-1/CAIX Nanoparticles with Sequential pH/ROS Responsiveness Overcome Tumor Microenvironment Barriers for Enhanced Penetration and Antitumor Efficacy.","authors":"Zheng, Fen; Zhang, Shanming; Liu, Dongxuan; Chen, Yitong; Xu, Long","year":2025,"journal":"Biomacromolecules, 26(11), 7354-7366","doi":"10.1021/acs.biomac.5c00831","pmid":"41069061","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14601","title":"The Inhibitory Effect of Peptide Hydrolysate of Type I Collagen Derived from Pig Skin on Melanogenesis in B16F10 Melanoma Cells.","authors":"Zheng, Jialin; Xu, Dandan; Li, Tianduo","year":2025,"journal":"Biomolecules, 15(2)","doi":"10.3390/biom15020220","pmid":"40001523","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14602","title":"Phase I study of the oral GLP-1 receptor agonist DA-302168S: Safety, pharmacokinetics, and pharmacodynamics in healthy and overweight/obese adults.","authors":"Zheng, Liang; Yang, Yuanxun; Dong, Guangxin; Qin, Xiaolong; Li, Wenwen; Zhang, Yuwen; Li, Haiyan; Zhang, Shaofeng; He, Peng; Ye, Qijun; Yu, Zhou; Li, Yi; Li, Juan; Hu, Wei","year":2025,"journal":"Diabetes, obesity & metabolism, 27(12), 7525-7534","doi":"10.1111/dom.70159","pmid":"40994059","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14603","title":"Antimicrobial peptide DiPGLa-H exhibits the most outstanding anti-infective activity among the PGLa variants based on a systematic comparison.","authors":"Zheng, Liangjun; Zafir, Muhammad; Zhang, Ziqian; Ma, Yadong; Yang, Fengyi; Wang, Xiaokun; Xue, Xuemei; Wang, Chen; Li, Ping; Liu, Pilong; El-Gohary, Fatma A; Zhao, Xin; Xue, Huping","year":2025,"journal":"Applied and environmental microbiology, 91(3), e0206224","doi":"10.1128/aem.02062-24","pmid":"39907455","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"DiPGLa-H, a tandem-repeat variant of the frog-derived antimicrobial peptide PGLa, achieved a therapeutic index of 35.94 — meaning it kills bacteria at concentrations far below those that harm host cells. It was effective against E. coli, Staphylococcus aureus, and Acinetobacter baumannii, and disrupted biofilms formed by multiple pathogenic species.\n\nIn mouse peritoneal inflammation models, DiPGLa-H improved survival rates by 31–38% and reduced bacterial burdens in key organs by 100-fold to 1,000-fold. The peptide works by disrupting both inner and outer bacterial membranes, causing cell shrinkage, vesiculation, and intracellular content leakage.\n\nA DAMP4 fusion protein strategy combined with non-chromatographic purification achieved high-purity biosynthesis with yields of 21.2 mg/mL, enabling cost-effective large-scale production.","whyItMatters":"Antibiotic resistance is one of the biggest threats to global health, and antimicrobial peptides are among the most promising alternatives. However, most AMPs fail clinically because they are too weak, too toxic, or too expensive to produce. This study addresses all three problems: DiPGLa-H is potent and selective, safe for mammalian cells, and can be manufactured cost-effectively. The systematic comparison of nine variants also provides valuable structure-activity relationship data for designing future AMPs.","specificNumbers":"","methodology":"The researchers designed and synthesized nine variants of PGLa and characterized their structure (all retained α-helical conformations), biocompatibility (hemolysis and macrophage toxicity assays), and antimicrobial activity (minimum inhibitory concentration testing against key pathogens). They assessed membrane disruption mechanisms using microscopy and leakage assays. Biofilm disruption was tested against multiple species. In vivo efficacy was evaluated in a mouse peritoneal inflammation model, measuring survival rates and organ bacterial burdens. A DAMP4 fusion protein approach with acid cleavage and non-chromatographic purification was developed for scalable production.","limitations":"The in vivo testing was limited to a mouse peritoneal inflammation model, which may not represent all clinical infection scenarios. Long-term toxicity, pharmacokinetics, and resistance development were not assessed. The study did not test DiPGLa-H against a comprehensive panel of clinical multidrug-resistant isolates. Stability in human biological fluids (serum, wound fluid) was not specifically evaluated, though pH and temperature stability were demonstrated."},{"rthcId":"RPEP-14604","title":"Exploring new therapeutic drugs for osteoarthritis and osteoporosis: Glucagon-like peptide-1 receptor agonists: A review.","authors":"Zheng, Meiqi; Zhao, Jingjing; Wang, Yuxuan; Cui, Zifan; Qiao, Zihong; Wu, Hongzhuo; Shi, Chenxia; Wang, Xiaofeng","year":2025,"journal":"Medicine, 104(29), e43239","doi":"10.1097/MD.0000000000043239","pmid":"40696619","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 receptor agonists affect bone metabolism through multiple mechanisms relevant to both osteoarthritis and osteoporosis. These include anti-inflammatory effects, modulation of chondrocyte matrix metabolism (protecting cartilage), analgesic properties, promotion of bone formation, inhibition of bone resorption, and reduced fracture incidence. The review synthesizes evidence suggesting GLP-1RAs could serve as a dual-purpose therapeutic for these commonly co-occurring conditions.","whyItMatters":"Osteoarthritis and osteoporosis together affect hundreds of millions of people worldwide, often co-occurring in older adults. No current drug effectively treats both simultaneously. If GLP-1 drugs — already widely prescribed for diabetes and obesity — can also protect bones and joints, this could represent a major therapeutic advance with minimal additional drug development costs.","specificNumbers":"","methodology":"This is a narrative review summarizing the current literature on GLP-1 receptor agonists' mechanisms of action on bone metabolism, including their effects on inflammation, cartilage, bone formation, bone resorption, and fracture risk in the context of osteoarthritis and osteoporosis.","limitations":"As a narrative review, this does not perform a systematic search or meta-analysis. Most evidence for GLP-1RA effects on bone comes from preclinical studies or secondary analyses of diabetes trials, not dedicated bone/joint clinical trials. The mechanisms described may not translate into clinically meaningful benefits for osteoarthritis and osteoporosis patients specifically. No specific numbers or effect sizes are reported in the abstract."},{"rthcId":"RPEP-14605","title":"Traditional Chinese medicine acupoint pasting for preventing and treating gastrointestinal reactions in type II diabetes mellitus patients undergoing glucagon-like peptide-1 receptor agonist therapy: A clinical study.","authors":"Zheng, Songsong; Zhou, Diyi; Chen, Fangfang; Zheng, Jiandi","year":2025,"journal":"Journal of medical biochemistry, 44(6), 1331-1339","doi":"10.5937/jomb0-55092","pmid":"41054590","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14606","title":"Clinical efficacy and safety analysis of minimally invasive tube placement, aspiration, liquefaction and drainage surgery for patients with cerebral hemorrhage.","authors":"Zheng, Weixin; Lin, Hong; Zheng, Zongliao; Huang, Yan; Wang, Qikun; Wang, Weiwei; Yang, Yong","year":2025,"journal":"American journal of translational research, 17(10), 8076-8086","doi":"10.62347/QSTW6376","pmid":"41268222","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14607","title":"Heart failure with preserved ejection fraction and obesity: emerging metabolic therapeutic strategies.","authors":"Zheng, Wenwen; Qi, Qianxian; Li, Jie; He, Chaojie; Fan, Hongyan","year":2025,"journal":"Diabetology & metabolic syndrome, 17(1), 336","doi":"10.1186/s13098-025-01917-z","pmid":"40826119","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14608","title":"Investigating the association between GLP-1 receptor agonists and mood disorders: A study integrating real-world data and Mendelian randomization.","authors":"Zheng, Xiulan; Wang, Hao; Liu, Ping; Pan, Jie; Lv, Rundong; Feng, Chen","year":2025,"journal":"European psychiatry : the journal of the Association of European Psychiatrists, 69(1), e6","doi":"10.1192/j.eurpsy.2025.10125","pmid":"41331950","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14609","title":"A systematic review on the role of glucagon-like peptide-1 receptor agonists on alcohol-related behaviors: potential therapeutic strategy for alcohol use disorder.","authors":"Zheng, Yang Jing; Soegiharto, Crystaleene; Au, Hezekiah C T; Valentino, Kyle; Le, Gia Han; Wong, Sabrina; Teopiz, Kayla M; Rhee, Taeho Greg; Guillen-Burgos, Hernan F; Cao, Bing; McIntyre, Roger S","year":2025,"journal":"Acta neuropsychiatrica, 37, e51","doi":"10.1017/neu.2025.6","pmid":"39969054","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14610","title":"An antimicrobial peptide as a potential therapy for bacterial pneumonia that alleviates antimicrobial resistance.","authors":"Zhong, Chao; He, Yongtao; Zou, Jing; Gao, Luyang; Wang, Jiahui; Zhu, Jingyi; Xue, Wenjing; Gou, Sanhu; Zhang, Yun; Liu, Hui; Ni, Jingman","year":2025,"journal":"Nature communications, 16(1), 10488","doi":"10.1038/s41467-025-65449-w","pmid":"41290594","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The linear peptide composed of four (D-Trp)-(D-Arg)-(D-Lys) repeating units demonstrated robust antimicrobial activity against multidrug-resistant bacteria including MRSA and Klebsiella pneumoniae, with high stability and improved biocompatibility compared to typical antimicrobial peptides.\n\nCritically, the peptide showed low potential for resistance development and the ability to alleviate existing resistance, restoring antibiotic sensitivity in resistant bacteria. This was attributed to its multiple simultaneous mechanisms: membrane targeting, non-membrane lysis through DNA binding, reactive oxygen species accumulation, ATP depletion, and metabolic interference. In vivo, the peptide showed therapeutic efficacy in both MRSA and K. pneumoniae pneumonia mouse models, as well as in a lipopolysaccharide-induced lung injury model.","whyItMatters":"Antimicrobial resistance is one of the greatest threats to global health, and pneumonia caused by drug-resistant bacteria is particularly deadly. This Nature Communications study addresses the crisis from two angles: the peptide not only kills resistant bacteria directly, but it can also reverse their resistance mechanisms and restore sensitivity to existing antibiotics. The multi-mechanism approach makes resistance development unlikely. The D-amino acid design provides stability that has limited many previous antimicrobial peptides.","specificNumbers":"","methodology":"Researchers designed a synthetic linear antimicrobial peptide using D-amino acids (which resist enzymatic degradation). Antimicrobial activity was tested against multidrug-resistant bacteria including MRSA and K. pneumoniae via standard susceptibility assays. Resistance development potential was assessed through serial passage experiments. Mechanisms of action were investigated through membrane integrity studies, DNA binding assays, ROS measurement, and ATP quantification. Biocompatibility was evaluated. In vivo efficacy was tested in mouse models of MRSA pneumonia, K. pneumoniae pneumonia, and LPS-induced lung injury.","limitations":"All efficacy data is preclinical (cell culture and mouse models). The abstract does not provide specific MIC values, survival rates, or other quantitative outcomes. Manufacturing costs and scalability for clinical use are not discussed. Pharmacokinetic properties (half-life, distribution, clearance) are not detailed. The mouse pneumonia model, while informative, may not fully predict human therapeutic outcomes. Long-term toxicity data is not described."},{"rthcId":"RPEP-14611","title":"Liraglutide attenuates high glucose-induced endothelial cell senescence and dysfunction via SIRT1-mediated deacetylation of p53/p65.","authors":"Zhong, Weili; Yang, Ying; Wang, Yanru","year":2025,"journal":"Tissue & cell, 95, 102882","doi":"10.1016/j.tice.2025.102882","pmid":"40198926","tags":["GLP-1-agonists","vascular-aging"],"studyType":"in-vitro","evidenceStrength":"low","keyFinding":"Liraglutide (a GLP-1 receptor agonist) protected human blood vessel cells from high-glucose-induced aging and dysfunction through a specific molecular pathway: SIRT1-mediated deacetylation of p53 and p65. At 1 μM concentration over 72 hours, liraglutide reduced cellular senescence markers, lowered reactive oxygen species (ROS) and oxidative stress, upregulated antioxidant defenses, and promoted new blood vessel formation and cell migration (all p<0.05).\n\nCritically, when SIRT1 was knocked down, liraglutide's protective effects were diminished; when SIRT1 was overexpressed, the effects were enhanced. This establishes SIRT1 as the key mediator — liraglutide protects blood vessels by activating the same longevity-associated protein that caloric restriction and exercise stimulate.","whyItMatters":"Diabetic patients have accelerated blood vessel aging, which drives heart attacks and strokes. GLP-1 drugs like liraglutide are already known to reduce cardiovascular events in diabetic patients, but the mechanism wasn't fully understood. This study identifies the SIRT1-p53/p65 axis as a key pathway, connecting GLP-1 drugs to the same longevity biology that has attracted enormous research interest in aging science.","specificNumbers":"30 mM glucose induction · 1 μM liraglutide · 72-hour treatment · p<0.05 for all endpoints · SIRT1-dependent effects","methodology":"In vitro study using human umbilical vein endothelial cells (HUVECs) exposed to high glucose (30 mM) to model diabetic vascular damage. Treated with liraglutide (1 μM) for 72 hours. SIRT1 overexpression and knockdown experiments confirmed the pathway. Assessed senescence markers, ROS, oxidative stress, antioxidant markers, angiogenesis, and migration by Western blot and functional assays.","limitations":"Cell culture study only — results from isolated endothelial cells in a dish may not reflect the complex in-vivo vascular environment. The 30 mM glucose concentration is supraphysiological. A single liraglutide concentration and timepoint were tested. Translation to human vascular aging requires animal and clinical studies."},{"rthcId":"RPEP-14612","title":"Association between GLP-1 receptor agonists as a class and colorectal cancer risk: a meta-analysis of retrospective cohort studies.","authors":"Zhong, Ying; Wu, Tingting; Khan, Najeeb Ullah","year":2025,"journal":"BMC gastroenterology, 25(1), 614","doi":"10.1186/s12876-025-04211-4","pmid":"40847331","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Seven retrospective cohort studies involving 5,066,681 patients were analyzed. The pooled analysis found a significantly increased colorectal cancer risk in GLP-1 RA users compared to the reference population (RR 2.31; 95% CI: 1.82-2.93; I² = 36%; p < 0.0001).\n\nHowever, when GLP-1 RA users were compared specifically to users of other diabetes drugs, the colorectal cancer incidence was not significantly different (OR 1.73; 95% CI: 0.21-14.18; p = 0.61; I² = 100%). The extremely wide confidence interval and 100% heterogeneity in this comparison indicate the data is highly inconsistent. Quality assessment showed low-to-moderate risk of bias across studies.","whyItMatters":"With tens of millions of people now taking GLP-1 drugs, even a small increased cancer risk would have enormous public health implications. This meta-analysis raises an important safety signal that demands further investigation. However, the nuanced finding — that the risk disappears when comparing to other diabetes drugs — suggests the association may be confounded by obesity and diabetes themselves, which are well-established colorectal cancer risk factors. This is exactly the kind of data that regulatory agencies and clinicians need to make informed prescribing decisions.","specificNumbers":"","methodology":"Systematic review and meta-analysis following PRISMA guidelines. Researchers searched PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov from inception to December 2024. Seven retrospective cohort studies analyzing GLP-1 RA effects on colorectal cancer risk in type 2 diabetes patients were included. Study quality was assessed using the Newcastle-Ottawa Scale. Random-effects models were used for pooled analysis, with heterogeneity evaluated by I² statistic.","limitations":"All 7 included studies were retrospective cohort studies, which cannot prove causation and are susceptible to confounding. Obesity and diabetes — the conditions requiring GLP-1 treatment — are themselves major colorectal cancer risk factors, creating inherent confounding. The comparison to other drugs showed 100% heterogeneity, indicating highly inconsistent results across studies. The duration of GLP-1 RA exposure and specific drugs used were not consistently reported. No dose-response analysis was possible. The data cannot distinguish whether GLP-1 drugs increase cancer risk or whether detection bias (more medical monitoring in treated patients) explains the findings."},{"rthcId":"RPEP-14613","title":"Novel Aptamers Targeting Sclerostin Loop3 Improve Skeletal and Muscle Properties Without Adverse Cardiovascular Effects in Orchiectomized Mice.","authors":"Zhou, Bingna; Hu, Jing; Yu, Yuanyuan; Sun, Lei; Wang, Yanye; Zhang, Qian; Jiang, Yan; Wang, Ou; Xing, Xiaoping; Xia, Weibo; Wang, Luyao; Zhang, Ge; Li, Mei","year":2025,"journal":"Journal of cachexia, sarcopenia and muscle, 16(3), e13831","doi":"10.1002/jcsm.13831","pmid":"40464222","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14614","title":"Glucose-dependent insulinotropic peptide and beyond: co-agonist innovations in the treatment of metabolic diseases.","authors":"Zhou, Chenxu; Gong, Binbin; Liu, Xiyu; Hu, Guoqiang; Sun, Lidan","year":2025,"journal":"European journal of pharmacology, 999, 177681","doi":"10.1016/j.ejphar.2025.177681","pmid":"40306536","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14615","title":"Phyllosphere microbiomes in grassland plants harbor a vast reservoir of novel antimicrobial peptides and biosynthetic diversity.","authors":"Zhou, Hongzhang; Gao, Yu; Wu, Baiyila; Xu, Gang; Tian, Limei; Sun, Yunlei; Yang, Fuyu; Ni, Kuikui","year":2025,"journal":"Journal of advanced research","doi":"10.1016/j.jare.2025.12.017","pmid":"41391818","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"From over 68 million non-redundant gene sequences obtained through ultra-deep metagenomic sequencing of grassland plant phyllosphere microbiomes, researchers identified 885,396 potential antimicrobial peptides (AMPs). Of these, 99.76% were previously uncharacterized.\n\nThe researchers reconstructed hundreds of near-complete bacterial genomes, with 32.61% representing unclassified species. Of the biosynthetic gene clusters (BGCs) found in these genomes, 91.97% were also previously unknown.\n\nHost plant family significantly influenced microbial biosynthetic capacity. Pseudomonas genomes associated with grasses (Poaceae) contained an average of 28 BGCs, significantly more than those associated with daisy-family plants (Asteraceae, mean = 14.76, p = 0.033).\n\nCritically, all 13 AMPs synthesized via solid-phase peptide synthesis demonstrated real antimicrobial activity, each inhibiting at least one tested bacterial strain.","whyItMatters":"With antibiotic resistance rising globally, finding new sources of antimicrobial compounds is urgent. This study reveals that the microbes living on ordinary grassland plants represent a vast, largely untapped reservoir of potential new antibiotics. The fact that all tested candidates showed real activity suggests this isn't just a theoretical resource — it could yield practical new antimicrobial drugs.","specificNumbers":"","methodology":"Researchers collected 221 grassland plant samples spanning 45 plant families and performed ultra-deep metagenomic sequencing to characterize the microbial communities on plant surfaces (phyllosphere). They used computational analysis to identify biosynthetic gene clusters and potential antimicrobial peptides, reconstructed near-complete bacterial genomes from the metagenomic data, and performed host phylogenetic analysis. To validate their findings, they chemically synthesized 13 candidate AMPs and tested them against bacterial strains in bioactivity assays.","limitations":"Only 13 of the 885,396 identified peptide candidates were actually synthesized and tested, leaving the vast majority unvalidated. The antimicrobial testing was limited to a few bacterial strains and did not assess toxicity, stability, or efficacy in living organisms. The study focused on grassland ecosystems, and findings may not generalize to other environments. Computational predictions of AMPs may include false positives."},{"rthcId":"RPEP-14616","title":"Risk of ophthalmic adverse drug reactions in patients prescribed glucagon-like peptide 1 receptor agonists: a pharmacovigilance study based on the FDA adverse event reporting system database.","authors":"Zhou, Jianxing; Huang, Wei; Xie, Yunzhen; Shen, Haobin; Liu, Maobai; Wu, Xuemei","year":2025,"journal":"Endocrine, 88(1), 80-90","doi":"10.1007/s12020-024-04112-8","pmid":"39578328","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14617","title":"Cationic amino acid-engineered peptide hydrogels for sustained and potent antigen delivery enabling single-administration vaccination.","authors":"Zhou, Jingjing; Yu, Jiaxi; Zhang, Shengying; Teng, Zhidong; Zang, Haoyue; Zhang, Mingyang; Sun, Shiqi; Guo, Huichen","year":2025,"journal":"Nanoscale, 17(47), 27506-27521","doi":"10.1039/d5nr03790e","pmid":"41269068","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14618","title":"The efficacy and safety of danuglipron and orforglipron in patients with type 2 diabetes and obesity: a systematic review and meta-analysis.","authors":"Zhou, Jingjing; Wang, Fang; Li, Sen","year":2025,"journal":"Frontiers in endocrinology, 16, 1646956","doi":"10.3389/fendo.2025.1646956","pmid":"41450584","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14619","title":"Effect of semaglutide versus placebo on cardiorenal outcomes by prior cardiovascular disease and baseline body mass index: Pooled post hoc analysis of SUSTAIN 6 and PIONEER 6.","authors":"Zhou, Jingmin; Husain, Mansoor; Li, Yang; Liu, Wenyan; Shen, Zewei; Vilsbøll, Tina; Ge, Junbo","year":2025,"journal":"Diabetes, obesity & metabolism, 27(10), 5706-5715","doi":"10.1111/dom.16621","pmid":"40704485","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14620","title":"Information pharmacists assist in the construction of GLP-1RA prescription review rules in a tertiary hospital in China.","authors":"Zhou, Li; Duanmu, Wenjing; Tan, Feilong; Gu, Xi; Che, Hongyi; Yin, Wenjie","year":2025,"journal":"BMC health services research, 25(1), 1276","doi":"10.1186/s12913-025-13377-2","pmid":"41034888","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14621","title":"Biophysical and simulation analysis of ACE tripeptide inhibitors derived from milk.","authors":"Zhou, Qian; Liao, Dankui; Wang, Lei; Sun, Lixia; Tong, Zhangfa; Sun, Jianhua; Lan, Xiongdiao; Zhou, Guangzhi","year":2025,"journal":"Food chemistry, 493(Pt 1), 145633","doi":"10.1016/j.foodchem.2025.145633","pmid":"40737925","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14622","title":"Structural pharmacology and mechanisms of GLP-1R signaling.","authors":"Zhou, Qingtong; Zhao, Fenghui; Zhang, Yao; Yang, Dehua; Wang, Ming-Wei","year":2025,"journal":"Trends in pharmacological sciences, 46(5), 422-436","doi":"10.1016/j.tips.2025.03.003","pmid":"40221226","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14623","title":"Weight Loss Blockbuster Development: A Role for Unimolecular Polypharmacology.","authors":"Zhou, Qingtong; Li, Guanyi; Hang, Kaini; Li, Jie; Yang, Dehua; Wang, Ming-Wei","year":2025,"journal":"Annual review of pharmacology and toxicology, 65(1), 191-213","doi":"10.1146/annurev-pharmtox-061324-011832","pmid":"39259982","tags":["glp-1","multi-agonist"],"studyType":"review","evidenceStrength":"strong","keyFinding":"This review examines how unimolecular polypharmacology — designing single molecules that hit multiple receptors simultaneously — has transformed obesity and diabetes treatment. Blockbuster drugs like tirzepatide (GLP-1/GIP dual agonist) and retatrutide (GLP-1/GIP/glucagon triple agonist) have achieved unprecedented weight loss and blood sugar control, surpassing what single-receptor agonists can do.\n\nTirzepatide in particular has demonstrated remarkable effectiveness for weight loss, glycemic control, and additional cardiovascular and kidney benefits. However, the review also addresses ongoing challenges: gastrointestinal side effects, patient compliance (particularly with injections), and the problem of weight rebound when treatment stops.","whyItMatters":"With over 2.5 billion adults affected by obesity and type 2 diabetes globally, the development of multi-receptor agonists represents one of the most important pharmaceutical advances in decades. This review from Annual Review of Pharmacology and Toxicology provides a comprehensive framework for understanding why targeting multiple receptors with a single molecule works better than hitting just one — and what challenges remain before these drugs reach their full potential.","specificNumbers":"2.5 billion adults affected by obesity/T2DM · Tirzepatide: dual GLP-1/GIP agonist · Retatrutide: triple GLP-1/GIP/glucagon agonist · Superior efficacy vs single agonists","methodology":"This is a comprehensive review article published in Annual Review of Pharmacology and Toxicology, covering the development, mechanisms, clinical efficacy, and challenges of unimolecular multi-receptor agonists for metabolic diseases.","limitations":"As a review, it synthesizes existing literature rather than presenting new data. The field is moving extremely fast, and clinical trial results continue to emerge. Long-term safety data for these newer multi-agonists is still limited. The review acknowledges but may understate the significance of weight rebound and GI side effect challenges."},{"rthcId":"RPEP-14624","title":"Biomarkers predicting postoperative adverse outcomes in children with congenital heart disease: a systematic review and meta-analysis.","authors":"Zhou, Shifan; Liu, Lu; Jin, Xiaochuang; Dorikun, Daniel; Ma, Songfeng","year":2025,"journal":"Frontiers in pediatrics, 13, 1508329","doi":"10.3389/fped.2025.1508329","pmid":"39896721","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14625","title":"Virus-Like Particle-Based Personalized Neoantigen Nano-Vaccine for Tumor Immunotherapy and Recurrence Prevention.","authors":"Zhou, Shujun; Wang, Chufan; Ning, Yuxiang; Wang, Yunhao; Xin, Fei; Ren, Lei; Wang, Yanfeng","year":2025,"journal":"ACS nano, 19(40), 35385-35400","doi":"10.1021/acsnano.5c06278","pmid":"41032465","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14626","title":"Combined cancer immunotherapy with lipid nanoparticle delivery of oligo-based cGAS-agonistic adjuvant and peptide or mRNA vaccines.","authors":"Zhou, Shurong; Liang, Yuqing; Hao, Yu; Wang, Qiyan; Xu, You; Su, Ting; Cheng, Furong; Zhu, Guizhi","year":2025,"journal":"Molecular therapy. Nucleic acids, 36(3), 102623","doi":"10.1016/j.omtn.2025.102623","pmid":"40704024","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14627","title":"Synthetic helical peptides on nanofibers to activate cell-surface receptors and synergistically enhance critical-sized bone defect regeneration.","authors":"Zhou, Tongqing; C Cavalcante, Rafael; Ge, Chunxi; Franceschi, Renny T; Ma, Peter X","year":2025,"journal":"Bioactive materials, 43, 98-113","doi":"10.1016/j.bioactmat.2024.08.017","pmid":"39381328","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14628","title":"Biodegradable and anti-swelling peptide-based supermolecule hydrogel for eliminating ROS and inhibiting inflammation in acute spinal cord injury repair.","authors":"Zhou, Xiaolin; Guo, Yanqiu; Gao, Zhan; Lv, Gan; Wang, Xiangyang; Zhang, Mengpei; Zhou, Yunlong","year":2025,"journal":"Acta biomaterialia, 205, 193-204","doi":"10.1016/j.actbio.2025.08.043","pmid":"40882906","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The FFFGHK peptide self-assembled into an injectable, biodegradable, anti-swelling supramolecular hydrogel that demonstrated multiple therapeutic effects:\n\nIn vitro: eliminated reactive oxygen species (ROS), inhibited inflammatory responses, rescued cell apoptosis, accelerated neuron adhesion and proliferation, and promoted differentiation of neural stem cells into neurons.\n\nIn vivo (rats with SCI): significantly enhanced recovery of autonomous motor functions and signal transduction, and promoted neuronal regeneration at the injury site. The single-component design — combining the self-assembling phenylalanine (FFF) motif with the bioactive GHK tripeptide — created a material that serves simultaneously as a structural scaffold and a therapeutic agent.","whyItMatters":"Spinal cord injury affects hundreds of thousands of people annually worldwide, and there are currently no effective treatments that restore function. This peptide hydrogel addresses multiple barriers to recovery simultaneously: it fights the toxic environment (ROS, inflammation) that prevents healing while providing a physical scaffold and biological signals that promote nerve regeneration. The simplicity of the design — a single six-amino-acid peptide — makes it potentially scalable and translatable.","specificNumbers":"","methodology":"The FFFGHK peptide was synthesized and characterized for self-assembly into a supramolecular hydrogel. In vitro experiments in cell culture assessed ROS elimination, anti-inflammatory effects, anti-apoptotic activity, neuron adhesion/proliferation, and neural stem cell differentiation. In vivo efficacy was tested in a rat spinal cord injury model, evaluating motor function recovery, electrophysiological signal transduction, and neuronal regeneration at the injury site.","limitations":"The in vivo study was conducted in a rat SCI model, which has significant anatomical and physiological differences from human spinal cord injuries. Specific quantitative data on motor recovery scores and sample sizes were not provided in the abstract. Long-term outcomes beyond the study period were not assessed. The translation from rat to human SCI recovery faces major challenges given the differences in spinal cord anatomy and regenerative capacity. The anti-swelling mechanism was not fully characterized."},{"rthcId":"RPEP-14629","title":"Neuropeptide F interacts with its receptor and regulates the immune response of Sepiella japonica.","authors":"Zhou, Xu; Fang, Pei-Xuan; Qiu, Jia-Yin; Li, Shuang; Chi, Chang-Feng","year":2025,"journal":"Fish & shellfish immunology, 167, 110862","doi":"10.1016/j.fsi.2025.110862","pmid":"40915332","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14630","title":"Caveolin-1 negatively regulates the calcitonin receptor-like receptor and neuroinflammation in a female mouse model of migraine.","authors":"Zhou, Yanjie; Chen, Wu; Zhang, Yu; Yang, Liu; Lu, Fu; Yan, Wen; Xie, Qingfang; Huang, Ying; Huang, Wanbin; Wang, Lintao; Zeng, Ziming; Xiao, Zheman","year":2025,"journal":"Journal of neuroinflammation, 22(1), 134","doi":"10.1186/s12974-025-03466-8","pmid":"40399967","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14631","title":"Long-Acting and Stapled GLP-1R/GIPR/GCGR Triple Agonist for the Treatment of Obesity and Atherosclerosis.","authors":"Zhou, Yaqi; Tu, Longfang; Wang, Xueying; Xu, Jiean; Xu, Shujing; Ning, Xiao; Xiong, Xiaochun; Zheng, Nan","year":2025,"journal":"Journal of medicinal chemistry, 68(15), 16578-16592","doi":"10.1021/acs.jmedchem.5c01399","pmid":"40707865","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The lead candidate UTG-4, a stapled triple agonist targeting GLP-1R/GIPR/GCGR, demonstrated enhanced efficacy over semaglutide (GLP-1R monoagonist) and tirzepatide (GLP-1R/GIPR dual agonist) in obese mice across multiple endpoints: weight loss, food intake suppression, glucose tolerance, and liver health. In Apoe knockout mice (a model of atherosclerosis), UTG-4 showed remarkable anti-atherosclerotic effects. Mechanistically, UTG-4 alleviated endothelial-to-mesenchymal transition in human aortic endothelial cells — a key process driving atherosclerosis progression. The peptide achieved balanced bioactivity across all three receptor targets comparable to their native ligands, with improved pharmacokinetic properties.","whyItMatters":"The race to build on GLP-1 drug success is one of the biggest stories in pharmaceutical development. Triple agonists represent the next frontier — adding glucagon receptor activation to the GLP-1/GIP dual agonism of tirzepatide. If UTG-4's superiority over both semaglutide and tirzepatide translates to humans, it could become the most potent anti-obesity peptide drug yet. The atherosclerosis benefit adds a cardiovascular dimension that goes beyond weight loss alone.","specificNumbers":"","methodology":"Researchers used a solid-phase Ugi macrocyclization strategy to synthesize stapled peptides with a side-chain protractor (for long-acting duration) attached to the exocyclic lactam bridge. They tested receptor activation using bioactivity assays, assessed pharmacokinetics, and evaluated efficacy in diet-induced obese mice (comparing to semaglutide and tirzepatide) and Apoe knockout mice (atherosclerosis model). Mechanistic studies used human aortic endothelial cells to assess endothelial-to-mesenchymal transition.","limitations":"This is a preclinical mouse study — the efficacy advantages over semaglutide and tirzepatide in mice may not translate proportionally to humans. No human safety or efficacy data exist for UTG-4. The atherosclerosis model (Apoe knockout) is a genetic model that may not perfectly replicate human disease. Specific quantitative outcomes (percent weight loss, dose levels) were not detailed in the abstract. Long-term safety of simultaneous triple receptor activation is unknown."},{"rthcId":"RPEP-14632","title":"The neuro-cutaneous axis: the role of nerve cells in wound healing.","authors":"Zhou, Yijing; Yang, Jin; Chen, Lin; Yu, Qin; Yang, Yafei","year":2025,"journal":"Biochemical and biophysical research communications, 793, 153038","doi":"10.1016/j.bbrc.2025.153038","pmid":"41275792","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14633","title":"Machine learning-guided anti-photoaging peptides from Chinese giant salamander skin: Efficient preparation and mechanistic insights.","authors":"Zhou, Yongjie; Zhang, Huijuan; Zhao, Chunyue; Fu, Zixin; Wang, Yuting; Chang, Sam K C; Zhang, Yan; Hong, Hui; Luo, Yongkang; Li, Bo; Tan, Yuqing","year":2025,"journal":"Food chemistry, 492(Pt 2), 145520","doi":"10.1016/j.foodchem.2025.145520","pmid":"40680662","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14634","title":"Screening and preliminary analysis of antimicrobial peptide genes in Octopussinensis.","authors":"Zhou, Yuquan; Chen, Zebin; Zou, Yihua; Qin, Yongjie; Jiang, Yonghua; Zou, Pengfei; Zhang, Jianming; Zhu, Youfang; Zhang, Ziping; Wang, Yilei","year":2025,"journal":"Fish & shellfish immunology, 163, 110408","doi":"10.1016/j.fsi.2025.110408","pmid":"40360041","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14635","title":"A novel antimicrobial peptide Larimicin78-102 from large yellow croaker (Larimichthys crocea) shows potent antibacterial activity in vitro and enhances resistance to vibrio fluvialis infection in vivo.","authors":"Zhou, Zhenzhen; Chen, Fangyi; Hao, Hua; Wang, Ke-Jian","year":2025,"journal":"Fish & shellfish immunology, 161, 110279","doi":"10.1016/j.fsi.2025.110279","pmid":"40089087","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Larimicin78-102 demonstrated broad-spectrum antibacterial activity against common aquatic pathogens including Vibrio fluvialis, Pseudomonas fluorescens, and Pseudomonas putida, plus anti-biofilm activity against all three. The peptide killed bacteria by disrupting both outer and inner cell membranes, causing ATP leakage and intracellular reactive oxygen species (ROS) accumulation.\n\nIn vivo, Larimicin78-102 raised survival of V. fluvialis-infected large yellow croaker to 95%. The peptide also modulated the immune response: it reduced pro-inflammatory cytokines TNF-α and IL-1β while upregulating the anti-inflammatory factor IL-4. It boosted innate immune gene expression (piscidin, hepcidin, lysozyme) and enhanced lysozyme enzymatic activity. The peptide showed good thermal stability, cation tolerance, and no cytotoxicity or hemolytic activity.","whyItMatters":"Large yellow croaker is one of the most farmed fish species in China, and bacterial diseases like Vibrio infections cause massive economic losses. With antibiotic resistance growing and regulatory pressure to reduce antibiotic use in aquaculture, finding effective antimicrobial peptides from the fish's own immune system is a particularly elegant solution. The 95% survival rate, combined with dual antimicrobial and immunomodulatory properties, makes this peptide one of the most promising aquaculture AMP candidates reported.","specificNumbers":"","methodology":"The Larimicin gene was identified through genomic analysis of large yellow croaker (L. crocea). Tissue distribution and infection-induced expression were characterized. A truncated peptide (Larimicin78-102) was synthesized and tested for: antimicrobial activity (MIC assays), LPS binding affinity, biofilm disruption, membrane permeabilization, ATP leakage, ROS generation, thermal stability, cation tolerance, cytotoxicity, and hemolytic activity. In vivo efficacy was tested in L. crocea challenged with V. fluvialis. Immune gene expression and cytokine modulation were measured by RT-qPCR.","limitations":"The study is limited to aquaculture applications with a single fish species. Scalability and cost of peptide synthesis for commercial aquaculture use were not addressed. While no cytotoxicity was observed in vitro, long-term effects of repeated peptide administration on fish health are unknown. The 95% survival figure needs to be replicated across different infection doses and environmental conditions. Whether resistance to this peptide could develop with prolonged use was not tested."},{"rthcId":"RPEP-14636","title":"Glucagon-like peptide-1 receptor agonists in neurodegenerative diseases: Promises and challenges.","authors":"Zhou, Zhi Dong; Yi, Lingxiao; Popławska-Domaszewicz, Karolina; Chaudhuri, Kallol Ray; Jankovic, Joseph; Tan, Eng King","year":2025,"journal":"Pharmacological research, 216, 107770","doi":"10.1016/j.phrs.2025.107770","pmid":"40344943","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14637","title":"Application of Antimicrobial Peptides in Wound Dressings.","authors":"Zhu, Aoxun; Chen, Baiqi; Ma, Jing; Wang, Jiajia; Tang, Rongfang; Liu, Liangeng; Sun, Weixin; Zheng, Xingzhong; Pan, Guangtao","year":2025,"journal":"Drug design, development and therapy, 19, 8523-8539","doi":"10.2147/DDDT.S543233","pmid":"41001070","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14638","title":"A Robust Biosensor Based on Dual Loop Constrained Antifouling Peptide for Electrochemical Detection of Human Insulin like Growth Factor 1 in Blood.","authors":"Zhu, Baoping; Li, Yang; Wang, Wenqing; Cheng, Shujie; Han, Rui; Luo, Xiliang","year":2025,"journal":"Analytical chemistry, 97(21), 11231-11238","doi":"10.1021/acs.analchem.5c01274","pmid":"40394454","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14639","title":"Synergistic therapeutic strategies for metabolic dysfunction-associated steatohepatitis and type 2 diabetes mellitus: molecular insights and clinical advances.","authors":"Zhu, Bo","year":2025,"journal":"Frontiers in endocrinology, 16, 1753393","doi":"10.3389/fendo.2025.1753393","pmid":"41635536","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"MASH and T2DM share a bidirectional feedback loop: impaired hepatic insulin signaling (from fatty liver) worsens blood glucose control, while chronic hyperglycemia and insulin resistance further drive liver inflammation and fibrosis. Key cellular players include hepatocytes, Kupffer cells (liver macrophages), hepatic stellate cells (which produce scar tissue), and pancreatic β-cells.\n\nEmerging therapies targeting multiple pathways simultaneously show the most promise: GLP-1 receptor agonists and dual incretin agents address both metabolic and liver inflammation, while PPAR modulators, thyroid hormone receptor beta agonists (like resmetirom), FXR agonists, and FGF analogues target distinct but overlapping mechanisms. Non-coding RNAs were identified as important regulators of lipid metabolism and inflammation in both diseases.","whyItMatters":"MASH and type 2 diabetes frequently coexist, with each condition worsening the other. Historically, they've been treated by different specialists using different drugs. The recognition that synergistic therapies — drugs that simultaneously improve both liver disease and metabolic control — could break the destructive feedback loop represents a major shift in treatment philosophy. This is especially relevant as the MASH treatment landscape transforms with multiple new drug classes entering clinical use.","specificNumbers":"","methodology":"This is a narrative review synthesizing molecular, cellular, and clinical evidence on the overlap between MASH and type 2 diabetes. The author examined the biological mechanisms connecting the two diseases and surveyed current and emerging therapeutic approaches, including both pharmacological and lifestyle interventions.","limitations":"As a narrative review, this paper summarizes existing knowledge without generating new data or performing systematic analysis. The therapeutic landscape is rapidly evolving, and some emerging therapies discussed may have limited clinical evidence. The review focuses on molecular mechanisms and clinical advances but does not provide head-to-head comparisons between therapeutic approaches or specific treatment algorithms."},{"rthcId":"RPEP-14640","title":"Immunogenicity-Guided Design of an Acinetobacter baumanii Vaccine.","authors":"Zhu, Chenghua; Liang, Shuaiyuan; Yang, Ning; Li, Shan; Xue, Jianpeng; Zhou, Runlu; Hong, Xiuwen; Chen, Sixi; Gao, Nan; Du, Qiang; Huang, Jianling; Feng, Ganzhu; Du, Xingran","year":2025,"journal":"European journal of immunology, 55(7), e70019","doi":"10.1002/eji.70019","pmid":"40726064","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14641","title":"The prevention and management of chronic kidney disease among patients with metabolic syndrome.","authors":"Zhu, Doreen; Judge, Parminder K; Wanner, Christoph; Haynes, Richard; Herrington, William G","year":2025,"journal":"Kidney international, 107(5), 816-824","doi":"10.1016/j.kint.2024.12.021","pmid":"39986466","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14642","title":"Qili Qiangxin ameliorates chronic heart failure: a randomized clinical trial of biomarkers, inflammation, and cardiac outcomes.","authors":"Zhu, Feng; Hu, Rui; Lv, Chao; Wang, Jin; Du, Xuqin; Zeng, Xudong; Huang, Yuxuan; Ma, Yiming; Yang, Cheng; Guo, Fengjie","year":2025,"journal":"Frontiers in pharmacology, 16, 1605944","doi":"10.3389/fphar.2025.1605944","pmid":"41098835","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14643","title":"Calcitonin gene-related peptide antagonists in Raynaud's phenomenon: a disproportionality study based on real data and drug-gene network analysis.","authors":"Zhu, Haibin; Ma, Minghua; Tian, Weiwei; Wu, Tingting; Wang, Yan; Huo, Yan; Liao, Xiaolan","year":2025,"journal":"Naunyn-Schmiedeberg's archives of pharmacology","doi":"10.1007/s00210-025-04877-3","pmid":"41417215","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"From the FAERS database (Q2 2018 to Q1 2025), 149 adverse event reports linked CGRP antagonists to Raynaud's phenomenon across 7 drugs:\n\n- Erenumab had the most reports\n- Fremanezumab showed the strongest adverse event signal across all four statistical methods\n- Drug-gene network analysis identified key molecular nodes: AKT1, EGFR, ERBB2 for rimegepant\n- KEGG pathway analysis revealed PI3K signaling as the most likely mechanism for small molecule CGRP antagonists (rimegepant, atogepant, ubrogepant) inducing Raynaud's\n- The PI3K/AKT pathway connects CGRP blockade to vascular dysfunction\n\nThe authors recommend regular monitoring for Raynaud's in patients receiving CGRP antagonists, particularly those with underlying vascular dysfunction.","whyItMatters":"CGRP is a potent vasodilator — blocking it to treat migraines could theoretically cause blood vessel constriction elsewhere. This study provides the first systematic evidence that CGRP antagonists may trigger Raynaud's phenomenon, an important safety consideration for the millions of patients now taking these drugs for migraine prevention and treatment.","specificNumbers":"","methodology":"Disproportionality analysis of the FAERS database using four established signal detection methods. Gene targets of CGRP antagonists and Raynaud's were predicted using multiple databases. Protein-protein interaction (PPI) networks were built using STRING. KEGG pathway enrichment analysis identified potential mechanisms. Analysis covered Q2 2018 through Q1 2025.","limitations":"FAERS data is based on voluntary reporting and cannot establish causation — only a statistical signal. Reporting biases may affect which drugs appear more frequently. The 149 reports represent a small fraction of total CGRP antagonist users. The drug-gene network analysis is computational and requires experimental validation. Pre-existing vascular conditions in reported patients were not always documented."},{"rthcId":"RPEP-14644","title":"EnDM-CPP: A Multi-view Explainable Framework Based on Deep Learning and Machine Learning for Identifying Cell-Penetrating Peptides with Transformers and Analyzing Sequence Information.","authors":"Zhu, Lun; Chen, Zehua; Yang, Sen","year":2025,"journal":"Interdisciplinary sciences, computational life sciences, 17(3), 744-769","doi":"10.1007/s12539-024-00673-4","pmid":"39714579","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14645","title":"A mini-review on cathelicidin in fish: Gene expression, immune function, and evolutionary insights.","authors":"Zhu, Meihua; Yang, Yan; Huang, Bei; Huang, Wenshu","year":2025,"journal":"Fish & shellfish immunology, 165, 110463","doi":"10.1016/j.fsi.2025.110463","pmid":"40441664","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14646","title":"Exploring the role of ubiquitination modifications in migraine headaches.","authors":"Zhu, Qian; Yang, Jin; Shi, Lei; Zhang, Jieying; Zhang, Peng; Li, Junlong; Song, Xiaoli","year":2025,"journal":"Frontiers in immunology, 16, 1534389","doi":"10.3389/fimmu.2025.1534389","pmid":"39958329","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14647","title":"Heuristic energy-based cyclic peptide design.","authors":"Zhu, Qiyao; Mulligan, Vikram Khipple; Shasha, Dennis","year":2025,"journal":"PLoS computational biology, 21(4), e1012290","doi":"10.1371/journal.pcbi.1012290","pmid":"40305587","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14648","title":"Extracellular ATP increases agonist potency and reduces latency at class B G protein-coupled receptors.","authors":"Zhu, Shuying; Yuan, Alice; Duffy, Tristan; Kim, Brandon H; Ozawa, Takeaki; Dixon, S Jeffrey; Chidiac, Peter","year":2025,"journal":"Molecular pharmacology, 107(6), 100040","doi":"10.1016/j.molpha.2025.100040","pmid":"40378650","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14649","title":"The mechanism of liraglutide on promoting osteogenesis via macrophages polarization under the inflammatory and oxidative stress in osteoporosis.","authors":"Zhu, Siyu; Hu, Yue; Wang, Zelin; Tan, Qiangbo; Zang, Yaran; Zhang, Zijiao; Fu, Wenqi; He, Yuzhu; Dong, Hui; Liu, Huiying","year":2025,"journal":"Life sciences, 377, 123717","doi":"10.1016/j.lfs.2025.123717","pmid":"40436107","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14650","title":"Collagen Peptides Ameliorate Murine Chronic Colitis: Toward the Molecular Basis for Their Enhancement of Intestinal Epithelial Defenses Against Oxidative Stress.","authors":"Zhu, Suqin; Liu, Yan; Li, Yangguang; Guo, Xinyu; Zhao, Zifang; Yu, Jianwei; Zhao, Lerong; She, Wenhai; Zeng, Mingyong; Li, Shiyang; Wu, Haohao; Obadina, Adewale Olusegun","year":2025,"journal":"Molecular nutrition & food research, 69(20), e70177","doi":"10.1002/mnfr.70177","pmid":"40635250","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14651","title":"Efficacy of Sacubitril/Valsartan Combined With Metoprolol on Cardiac Function, Cardiac Remodeling, and Endothelial Function in Patients With Coronary Heart Disease and Heart Failure.","authors":"Zhu, Tongyu; Song, Yingjing","year":2025,"journal":"British journal of hospital medicine (London, England : 2005), 86(4), 1-16","doi":"10.12968/hmed.2025.0120","pmid":"40265535","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14652","title":"Liraglutide alleviates diabetic cardiomyopathy in streptozotocin-induced diabetic rats by enhancing mitophagy mediated by the AMPK-Parkin signaling pathway.","authors":"Zhu, Ya-Xin; Zhang, Wei; Qu, Hui-Lin; Zhang, Yue; Zhou, Ruo-Qian; Li, Ping; Wang, Fang; Zhang, Yan; Liu, Hui-Hui; Li, Sha; Dong, Qian; Dou, Ke-Fei; Guo, Yuan-Lin; Li, Jian-Jun; Xu, Rui-Xia","year":2025,"journal":"World journal of diabetes, 16(12), 112423","doi":"10.4239/wjd.v16.i12.112423","pmid":"41480600","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14653","title":"Semaglutide ameliorates diabetes-associated cognitive dysfunction in mouse model of type 2 diabetes.","authors":"Zhu, Yan; He, Yi; Yang, Hongyan; Gao, Yanbo; Wang, Yan; Liu, Peiqing; Zhang, Mengjuan","year":2025,"journal":"PloS one, 20(7), e0326897","doi":"10.1371/journal.pone.0326897","pmid":"40608828","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14654","title":"Chronic cardiorenal syndrome: cardio-renal protective effect of SGLT2i.","authors":"Zhu, Yixin; Lv, Chenxi; Yang, Hanqi; Lu, Qian; Wang, XuChen; Zhang, Yueqi; Guo, Maojuan; Yang, Bo","year":2025,"journal":"Renal failure, 47(1), 2575921","doi":"10.1080/0886022X.2025.2575921","pmid":"41285492","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14655","title":"Edible Yellow Mealworm-Derived Antidiabetic Peptides: Dual Modulation of α-Glucosidase and Dipeptidyl-Peptidase IV Inhibition Revealed by Integrated Proteomics, Bioassays, and Molecular Docking Analysis.","authors":"Zhu, Yuying; Zhou, Enning; Tang, Yingran; Li, Qiangqiang; Wu, Liming","year":2025,"journal":"Foods (Basel, Switzerland), 15(1)","doi":"10.3390/foods15010096","pmid":"41517166","tags":[],"studyType":"in-vitro","evidenceStrength":"low","keyFinding":"Six unique peptides derived from yellow mealworm larvae (Tenebrio molitor) simultaneously inhibited two key diabetes-related enzymes: α-glucosidase (which breaks down carbohydrates into sugar) and DPP-IV (which degrades the GLP-1 hormone). The peptides — designated DK-7, WK-6, GR-7, FK-8, SK-6, and DK-8 — also enhanced glucose uptake in insulin-resistant liver cells (HepG2).\n\nMolecular docking revealed how the peptides bind to both enzymes through hydrogen bonds and hydrophobic interactions at specific active site residues, establishing a dual-target inhibition mechanism from a single food-derived peptide source.","whyItMatters":"DPP-IV inhibitors (like sitagliptin) and α-glucosidase inhibitors (like acarbose) are existing diabetes drug classes. Finding natural peptides from an edible, sustainable protein source that hit both targets simultaneously could lead to functional foods or supplements that help manage blood sugar through multiple mechanisms — with potentially fewer side effects than synthetic drugs.","specificNumbers":"6 unique peptides identified · Dual inhibition of α-glucosidase + DPP-IV · Enhanced glucose consumption in insulin-resistant HepG2 cells · Binding at 7 α-glucosidase residues + 5 DPP-IV residues","methodology":"Researchers used proteomics-guided screening to identify bioactive peptides from yellow mealworm (Tenebrio molitor) larvae. Six candidate peptides were tested for α-glucosidase inhibition, DPP-IV inhibition, and glucose consumption enhancement in insulin-resistant HepG2 liver cells. Molecular docking analysis characterized the binding interactions between peptides and both target enzymes.","limitations":"Entirely in vitro — no animal or human studies. Enzyme inhibition in a test tube doesn't guarantee the same activity when peptides are consumed orally (they may be degraded during digestion). Molecular docking is a computational prediction, not proof of actual binding in a biological system. The study doesn't address bioavailability, absorption, or effective oral doses."},{"rthcId":"RPEP-14656","title":"Hedonic eating is controlled by dopamine neurons that oppose GLP-1R satiety.","authors":"Zhu, Zhenggang; Gong, Rong; Rodriguez, Vicente; Quach, Kathleen T; Chen, Xinyu; Sternson, Scott M","year":2025,"journal":"Science (New York, N.Y.), 387(6741), eadt0773","doi":"10.1126/science.adt0773","pmid":"40146831","tags":[],"studyType":"Basic Research (Mouse Neuroscience)","evidenceStrength":"Moderate-High","keyFinding":"Researchers discovered the neural circuit that drives hedonic eating — consuming palatable food purely for pleasure, not hunger. A specific pathway from the peri-locus ceruleus to VTA dopamine neurons controls this behavior: these neurons encode how tasty food is and drive continued consumption.\n\nCritically for the GLP-1 drug field, semaglutide initially suppressed these dopamine neurons during food consumption, but mice developed tolerance — recovering both their palatable food appetite and dopamine neuron activity during repeated semaglutide treatment. When researchers artificially inhibited these dopamine neurons during eating, the tolerance was reversed. This reveals that the dopamine pleasure system actively fights against semaglutide's appetite-suppressing effects.","whyItMatters":"This Science paper answers two major questions about GLP-1 drugs. First, it explains WHY semaglutide reduces the pleasure of eating — it suppresses the dopamine neurons that encode food palatability. Second, and perhaps more importantly, it reveals a mechanism for weight loss plateau and potential regain: the dopamine system adapts to fight back against the drug's appetite suppression. Understanding this opponent process could lead to combination therapies that prevent tolerance to GLP-1 agonists.","specificNumbers":"Peri-locus ceruleus → VTA dopamine pathway identified · VTADA neurons encode palatability · Semaglutide suppresses VTADA responsiveness · Tolerance develops with repeated dosing · VTADA inhibition reverses tolerance","methodology":"The researchers used photometry-calibrated optogenetics — a cutting-edge technique that uses light to precisely control and measure individual neuron activity in living mice. They identified the neural pathway from the peri-locus ceruleus to VTA dopamine (VTADA) neurons, measured how these neurons respond to palatable food, tested the effect of semaglutide on this circuit, and then manipulated VTADA neuron activity to determine if it could reverse semaglutide tolerance.","limitations":"This is a mouse study — the specific neural circuits and their behavior may not perfectly translate to human brain physiology. The optogenetic manipulation used artificial stimulation/inhibition that doesn't replicate natural neural activity patterns. The semaglutide dosing regimen in mice may not reflect human pharmacokinetics or treatment duration. Human hedonic eating involves psychological and social factors beyond the dopamine circuit described here."},{"rthcId":"RPEP-14657","title":"The efficacy and safety of zavegepant nasal inhalation versus oral calcitonin-gene related peptide receptor antagonists in the acute treatment of migraine: a systematic review and network meta-analysis of the literature.","authors":"Zhu, Zixiang; Tang, Yanbing; Li, Longyuan; Ni, Hanyu; Liu, Meirong; Chen, Zhouqing; Wang, Zhong","year":2025,"journal":"The journal of headache and pain, 26(1), 48","doi":"10.1186/s10194-025-01984-7","pmid":"40065213","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 15 RCTs with 11,179 patients, zavegepant 10 mg nasal inhalation significantly outperformed placebo for pain freedom at 2 hours (RR = 1.54, 95% CI: 1.28-1.82) and most bothersome symptom freedom at 2 hours. However, zavegepant did not demonstrate significant superiority over oral CGRP receptor antagonists in either efficacy or long-term symptom relief. On safety, zavegepant 10 mg had more adverse events than placebo but was not inferior to oral gepants.","whyItMatters":"For migraine patients who struggle with oral medications (due to nausea, vomiting, or need for faster onset), a nasal spray alternative is clinically important. This meta-analysis clarifies that while zavegepant nasal spray is effective and safe, it doesn't outperform oral gepants — helping clinicians and patients make informed treatment decisions based on convenience and individual needs rather than expecting superior efficacy.","specificNumbers":"","methodology":"Systematic review and network meta-analysis searching PubMed, EMBASE, Cochrane, Scopus, and Web of Science through December 2024. Included only randomized controlled trials of CGRP receptor antagonists for acute migraine in adults, excluding non-randomized, non-English, or non-extractable data trials. Statistical analysis performed using STATA 18.0 and R Studio with network meta-analysis methodology enabling indirect comparisons between treatments.","limitations":"Network meta-analysis relies on indirect comparisons between drugs that weren't tested head-to-head, which introduces uncertainty. The included trials may have different designs, patient populations, and outcome definitions. Only English-language publications were included, potentially missing relevant data. The analysis focused on acute (single-attack) treatment and may not reflect real-world patterns of repeated use."},{"rthcId":"RPEP-14658","title":"Antiemetic effect of acupressure wristbands for GLP-1 medication associated nausea.","authors":"Ziemke, Florencia; Belarj, Soufiane; Esguerra, Jem; Reyes, Anita; Istfan, Nawfal","year":2025,"journal":"Obesity pillars, 15, 100178","doi":"10.1016/j.obpill.2025.100178","pmid":"40487675","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14659","title":"Effects of Tirzepatide on the Clinical Trajectory of Patients With Heart Failure, Preserved Ejection Fraction, and Obesity.","authors":"Zile, Michael R; Borlaug, Barry A; Kramer, Christopher M; Baum, Seth J; Litwin, Sheldon E; Menon, Venu; Ou, Yang; Weerakkody, Govinda J; Hurt, Karla C; Kanu, Chisom; Murakami, Masahiro; Packer, Milton","year":2025,"journal":"Circulation, 151(10), 656-668","doi":"10.1161/CIRCULATIONAHA.124.072679","pmid":"39556714","tags":["glp-1-agonists","cardiovascular"],"studyType":"rct","evidenceStrength":"strong","keyFinding":"In a double-blind randomized trial of 731 patients with heart failure with preserved ejection fraction (HFpEF) and obesity, tirzepatide (up to 15 mg weekly) produced comprehensive improvements across every clinical measure over a median of 104 weeks.\n\nCompared to placebo, tirzepatide reduced the combined risk of cardiovascular death or worsening heart failure events by 33–59% (hazard ratios 0.41–0.67 depending on analysis). At 52 weeks, tirzepatide improved the Kansas City Cardiomyopathy Questionnaire score by 6.9 points, increased 6-minute walk distance by 18.4 meters, improved quality of life (EQ-5D-5L), improved NYHA functional class, enhanced patient-reported well-being, and reduced heart failure medication burden. The hierarchical composite win ratio was 1.63, meaning tirzepatide patients were 63% more likely to have a better outcome than placebo patients.","whyItMatters":"Heart failure with preserved ejection fraction is one of the most common and difficult-to-treat forms of heart failure, especially in people with obesity. Until recently, few therapies showed meaningful benefit. This trial demonstrates that tirzepatide doesn't just help patients lose weight — it fundamentally improves their heart failure across multiple dimensions including survival, symptoms, exercise capacity, and quality of life. Published in Circulation, this represents some of the strongest evidence yet for GLP-1 class drugs in cardiovascular disease beyond diabetes.","specificNumbers":"n=731 · HR 0.41–0.67 for CV death/worsening HF · +6.9 pts KCCQ score · +18.4 m walk distance · Win ratio 1.63 · Median 104 weeks · BMI 38.2 · Age 65.2 years","methodology":"Double-blind, placebo-controlled randomized trial (SUMMIT trial). 731 patients with class II–IV heart failure, ejection fraction ≥50%, and BMI ≥30 were randomized to tirzepatide (titrated up to 15 mg subcutaneous weekly) or placebo added to standard heart failure therapy. Median follow-up was 104 weeks. Primary endpoints were the combined risk of cardiovascular death or worsening heart failure, and change in KCCQ Clinical Summary Score. Extended analyses included 6-minute walk distance, quality of life, NYHA class, medication burden, and a hierarchical composite.","limitations":"The study population was predominantly obese patients with HFpEF, so results may not generalize to heart failure with reduced ejection fraction or non-obese patients. The titrated dose of up to 15 mg is the maximum tirzepatide dose, which may not be tolerable for all patients. Gastrointestinal side effects typical of GLP-1 drugs were not detailed in this analysis."},{"rthcId":"RPEP-14660","title":"Vibrio cholerae serotype impacts pathogenicity.","authors":"Zingl, Franz G; Leitner, Deborah R; Fakoya, Bolutife; Morano, Alexander A; Waldor, Matthew K","year":2025,"journal":"bioRxiv : the preprint server for biology","doi":"10.64898/2025.12.23.696279","pmid":"41497622","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14661","title":"Skeletal Muscle Mass and Body Weight Fall Proportionally With Use of Dual Glucagon-Like Peptide 1/Glucose-Dependent Insulinotropic Polypeptide Receptor Agonist Tirzepatide: Case Report and Review of Literature.","authors":"Zinn, Jessica; Poretsky, Leonid","year":2025,"journal":"AACE clinical case reports, 11(2), 98-101","doi":"10.1016/j.aace.2024.12.001","pmid":"40201455","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A 68-year-old male with BMI 31.2 and HbA1c 5.9% was treated with tirzepatide. Results:\n\n- Total weight loss: 28.7 lbs (BMI dropped from 31.2 to 26.8)\n- Skeletal muscle mass loss: 9.9 lbs (34% of total weight loss)\n- Both body weight and muscle mass decreased by approximately 15% from baseline\n- HbA1c normalized from 5.9% to 5.3%\n\nThe proportional nature of the muscle loss — roughly matching the percentage of total weight lost — suggests muscle wasn't being disproportionately targeted. However, losing a third of all weight as muscle is still clinically significant, particularly in an older patient at risk for sarcopenia.","whyItMatters":"Muscle loss during rapid weight loss — sometimes called 'Ozempic muscle' — is a major clinical concern, especially for older adults who are already at risk of sarcopenia and frailty. While large tirzepatide trials report muscle loss, this is reportedly the first published case with multiple serial body composition measurements, providing a detailed time course of exactly when and how much muscle is lost. The finding that muscle loss tracks proportionally with total weight loss has practical implications for how clinicians counsel patients.","specificNumbers":"","methodology":"Serial body composition measurements were performed on a single patient throughout tirzepatide treatment. This is a case report documenting the time course and magnitude of changes in body weight, fat mass, and skeletal muscle mass. The specific body composition measurement method is not named in the abstract. The authors also reviewed existing literature on muscle loss with GLP-1 receptor agonists.","limitations":"This is a single case report (n=1), so the findings may not be generalizable to other patients, ages, body types, or dosing regimens. The patient was 68 years old — younger patients may have different muscle loss patterns. Exercise habits, protein intake, and other lifestyle factors that affect muscle preservation were not described. The specific body composition measurement technique is not detailed in the abstract, and different methods have varying accuracy for muscle mass."},{"rthcId":"RPEP-14662","title":"Decongestion in patients with advanced chronic kidney disease coexisting with heart failure.","authors":"Zoccali, Carmine; Levin, Adeera; Mallamaci, Francesca; Giugliano, Robert; De Caterina, Raffaele","year":2025,"journal":"Clinical kidney journal, 18(7), sfaf185","doi":"10.1093/ckj/sfaf185","pmid":"40612572","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14663","title":"Dipeptidyl peptidase-4 inhibitors enhance memory retention via neuropeptide Y.","authors":"Zoicas, Iulia; von Hörsten, Stephan; Plank, Anne-Christine; Kornhuber, Johannes","year":2025,"journal":"European journal of pharmacology, 996, 177556","doi":"10.1016/j.ejphar.2025.177556","pmid":"40139422","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14664","title":"Evaluation of antimicrobial and antibiofilm activities of peptide Impatiens balsamina-M1 and Zinc oxide nanoparticles against Helicobacter pylori.","authors":"Zolfaghari, Mina; Yadegar, Abbas; Rezaei, Atefe; Kazemi, Mohammad; Fazeli, Hossein; Tabesh, Elham; Karbasizade, Vajihe","year":2025,"journal":"Scientific reports, 16(1), 1723","doi":"10.1038/s41598-025-31310-9","pmid":"41366550","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14665","title":"The cost-effectiveness of semaglutide in reducing cardiovascular risk among people with overweight and obesity and existing cardiovascular disease, but without diabetes.","authors":"Zomer, Ella; Zhou, Jennifer; Nelson, Adam J; Sumithran, Priya; Nanayakkara, Shane; Ball, Jocasta; Kaye, David; Liew, Danny; Nicholls, Stephen J; Stub, Dion; Zoungas, Sophia","year":2025,"journal":"European heart journal. Quality of care & clinical outcomes, 11(6), 857-867","doi":"10.1093/ehjqcco/qcae063","pmid":"39096165","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14666","title":"Clinical efficacy of OS-01 peptide formulation in reducing the signs of periorbital skin aging.","authors":"Zonari, Alessandra; Brace, Lear E; Li, Fanghua; Harder, Nathaniel H O; Harker, Claire; Jacob, Carolyn; Kaufman, Joely; Chilukuri, Suneel; Oliveira, Carolina R; Boroni, Mariana; Carvalho, Juliana L","year":2025,"journal":"International journal of cosmetic science, 47(3), 455-465","doi":"10.1111/ics.13042","pmid":"39788697","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14667","title":"Recombinant Hydrophobic Polypeptide MBAY Loaded Into SPION-Exosome Realizes Sustained-Release to Improve Type 2 Diabetes Mellitus.","authors":"Zong, Xinyu; Xiao, Shangying; Xia, Haishan; Guo, Dan; Wu, Jiaping; Zhuang, Manjiao; Rao, Lei","year":2025,"journal":"Drug design, development and therapy, 19, 3103-3118","doi":"10.2147/DDDT.S499641","pmid":"40297314","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14668","title":"Cannabinoids rescue migraine symptoms caused by central CGRP administration in mice.","authors":"Zorrilla, Erik; Duong, Thomas L; Piña, Cassandra L; Russo, Andrew F","year":2025,"journal":"Cephalalgia : an international journal of headache, 45(11), 3331024251392103","doi":"10.1177/03331024251392103","pmid":"41182862","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Pretreatment with a 100:1 CBD:THC ratio (100 mg/kg CBD, 1 mg/kg THC) administered intraperitoneally rescued CGRP-induced light aversion in CD1 mice. The cannabinoid combination also rescued increased resting time in darkness, decreased zone transitions, and partially rescued decreased rearing behavior caused by centrally administered CGRP.\n\nImportantly, the automated squint assay showed that CBD:THC pretreatment partially rescued CGRP-induced spontaneous pain. An open field assay confirmed that the CGRP effects were migraine-specific (light aversion) rather than general anxiety, strengthening the specificity of both the migraine model and the cannabinoid rescue effect.","whyItMatters":"CGRP is the primary peptide target of modern migraine drugs (gepants and anti-CGRP antibodies), but not all patients respond to these treatments. If cannabinoids can independently counteract CGRP-driven migraine symptoms through the endocannabinoid system, this could open an entirely new therapeutic pathway — potentially helping patients who don't respond to direct CGRP blockade.","specificNumbers":"","methodology":"Researchers administered a 100:1 CBD:THC mixture intraperitoneally to CD1 mice 60 minutes before testing. CGRP was then injected intracerebroventricularly (directly into the brain) 30 minutes before behavioral assays. Three behavioral tests were used: a light/dark assay measuring light aversion and motility, an automated squint assay measuring spontaneous pain, and an open field assay to rule out general anxiety as a confound.","limitations":"This is a mouse study using direct brain injection of CGRP, which is a more extreme model than how migraines develop naturally in humans. The CBD:THC doses used (100 mg/kg CBD) are very high relative to typical human dosing and may not translate directly. Only one CBD:THC ratio was tested. The study used pretreatment rather than acute treatment, so it's unclear whether cannabinoids would help once migraine symptoms are already present."},{"rthcId":"RPEP-14669","title":"Combined effects of cannabidiol and Δ9-tetrahydrocannabinol alleviate migraine-like symptoms in mice.","authors":"Zorrilla, Erik; Krivoshein, Georgii; Kuburas, Adisa; Schenke, Maarten; Piña, Cassandra L; van Heiningen, Sandra H; Waite, Jayme S; Dehghani, Anisa; Castonguay, William C; Flinn, Harold C; van den Maagdenberg, Arn M J M; Russo, Andrew F; Tolner, Else A; Wattiez, Anne-Sophie","year":2025,"journal":"Cephalalgia : an international journal of headache, 45(2), 3331024251314487","doi":"10.1177/03331024251314487","pmid":"39988876","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14670","title":"Liraglutide Mitigates Renal Injury in Diabetic Kidney Disease by Suppressing Podocyte Cholesterol Accumulation Through mTOR/VMP1-Regulated Autophagy.","authors":"Zou, Qi; Li, Linlin; Ye, Hong; Chen, Qiaoling; Li, Binbin; Wei, Lixin","year":2025,"journal":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 39(22), e71229","doi":"10.1096/fj.202502041RRR","pmid":"41246995","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14671","title":"Understanding the activation mechanism of GLP-1R/GIPR by dual agonist Tirzepatide via molecular dynamics and protein-peptide binding.","authors":"Zou, Xuejun; He, Yu; Gao, Ya; Wang, Jian; Zhang, John Z H","year":2025,"journal":"International journal of biological macromolecules, 321(Pt 1), 146141","doi":"10.1016/j.ijbiomac.2025.146141","pmid":"40692063","tags":["tirzepatide","glp-1-receptor","gip-receptor"],"studyType":"computational","evidenceStrength":"moderate","keyFinding":"Molecular dynamics simulations revealed how tirzepatide activates both the GLP-1 and GIP receptors. The receptor activation involves a closure-to-open transition in the extracellular domain and movement of transmembrane helices — similar to how simpler class A receptors activate. Tirzepatide's conserved residues bind similarly to both receptors, but mutations in non-conserved residues create a biased binding pattern: C-terminal mutations weaken binding to GLP-1R, while N-terminal mutations strengthen binding to GIPR. This explains tirzepatide's dual-agonist profile at the molecular level.","whyItMatters":"Tirzepatide (Mounjaro/Zepbound) is the first dual GLP-1/GIP agonist to reach the market, but exactly how a single peptide activates two different receptors wasn't fully understood. This study reveals the molecular details — showing which parts of the tirzepatide molecule are responsible for each receptor interaction. This knowledge is essential for designing the next generation of dual and triple agonist peptide drugs.","specificNumbers":"C-terminal mutations weaken GLP-1R binding · N-terminal mutations enhance GIPR binding · ECD closure-open transition observed · Conserved residues bind similarly to both receptors","methodology":"The researchers used molecular dynamics (MD) simulations to model tirzepatide binding to GLP-1R and GIPR at atomic resolution. They tracked conformational changes in the receptors during activation and inactivation, analyzed binding characteristics at specific residue positions, and performed computational mutation studies to determine how changes in tirzepatide's amino acid sequence affect its affinity for each receptor.","limitations":"This is entirely a computational study — all findings are based on molecular simulations, not experimental measurements of actual binding or receptor activation. Molecular dynamics simulations depend on force field accuracy and simulation timescales, which may not capture all biologically relevant conformational states. The predictions about mutation effects need experimental validation."},{"rthcId":"RPEP-14672","title":"Efficacy and safety of once-weekly subcutaneous semaglutide 2.4 mg for the management of overweight or obesity in Asian populations: A systematic review, meta-analysis and meta-regression of randomised trials.","authors":"Zufry, Hendra; Hariyanto, Timotius Ivan","year":2025,"journal":"Diabetes, obesity & metabolism, 27(11), 6632-6643","doi":"10.1111/dom.70073","pmid":"40859897","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14673","title":"Use of glucagon-like peptide-1 receptor agonists and incretin mimetics for type 2 diabetes and obesity: A narrative review.","authors":"Zupec, Jason; Munger, Rebecca; Scaletta, Alice; Quinn, Diane H","year":2025,"journal":"Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition, 40(2), 327-349","doi":"10.1002/ncp.11279","pmid":"39961620","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Incretin mimetics, including GLP-1 and GIP receptor agonists, have achieved first-line treatment status for type 2 diabetes and obesity due to high efficacy and positive impact on comorbidities such as sleep apnea and heart failure. Multiple agents are available with varying durations of action, dosing frequencies, and delivery devices. Patients require education on proper administration, expected side effects, and nutrition considerations. Future developments include dual- and triple-mechanism agents and new oral formulations in a rapidly developing therapeutic pipeline.","whyItMatters":"GLP-1 receptor agonists represent one of the most important therapeutic advances in decades, transforming treatment for both diabetes and obesity. This review serves as a practical guide for healthcare providers managing patients on these medications, addressing not just efficacy data but the real-world challenges of dosing, side effects, and nutritional support that affect treatment success.","specificNumbers":"","methodology":"Narrative review of current literature covering FDA-approved indications of incretin mimetics, clinical evidence supporting their use, practical guidance for healthcare professionals, and the future therapeutic pipeline.","limitations":"This is a narrative review, not a systematic review or meta-analysis. It focuses on FDA-approved indications and the US healthcare context, which may not apply globally. The rapidly evolving pipeline means some information may quickly become outdated. Comparative effectiveness between different incretin mimetics is not comprehensively addressed. Long-term safety data for newer agents is still accumulating."},{"rthcId":"RPEP-14674","title":"Preliminary evaluation of oxyntomodulin as a biomarker for metabolic risk stratification in adults with obesity.","authors":"Zwierz, Mateusz; Buczyńska, Angelika; Kościuszko, Maria; Sobieska, Katarzyna; Adamska, Agnieszka; Siewko, Katarzyna; Krętowski, Adam Jacek; Popławska-Kita, Anna","year":2025,"journal":"Journal of translational medicine, 23(1), 1400","doi":"10.1186/s12967-025-07479-y","pmid":"41408640","tags":["obesity","biomarkers"],"studyType":"cross-sectional","evidenceStrength":"moderate","keyFinding":"Fasting oxyntomodulin (OXM) levels were significantly higher in obese individuals compared to overweight and healthy controls (p < 0.0001). OXM levels positively correlated with visceral fat mass and volume in the obese group.\n\nLogistic regression showed that higher OXM was significantly associated with increased risk of obesity and insulin resistance, particularly in more advanced stages of weight gain. The findings suggest OXM could serve as a measurable indicator of visceral adiposity and early metabolic dysfunction.","whyItMatters":"Oxyntomodulin is getting a lot of attention as a drug target — synthetic versions are being developed for weight loss. But this study flips the script and asks: what does your body's own oxyntomodulin tell us about metabolic health? The answer is that higher fasting levels of this gut peptide may flag visceral fat accumulation and insulin resistance before more serious complications develop. If validated, OXM could become a simple blood test to identify people at highest metabolic risk.","specificNumbers":"n=261 total (88 overweight, 134 obese, 39 healthy controls) · OXM significantly elevated in obese vs overweight and controls (p < 0.0001) · positive correlation with visceral adipose tissue mass and volume · higher OXM associated with increased insulin resistance risk","methodology":"A cross-sectional study comparing fasting oxyntomodulin levels across three groups: overweight adults (n=88), obese adults (n=134), and healthy controls (n=39). Body composition was measured using DXA scans and bioelectrical impedance. Researchers analyzed blood markers of glucose-insulin balance and lipid profiles, then used statistical modeling to assess whether OXM levels predicted obesity and insulin resistance.","limitations":"Cross-sectional design means it captures a single snapshot — it can't prove whether high OXM causes metabolic problems or results from them. The sample size of 261 is moderate. Only fasting OXM was measured, so the post-meal response wasn't captured. The study is preliminary and needs validation in larger, diverse populations."},{"rthcId":"RPEP-14675","title":"Post metabolic bariatric surgery weight regain: the importance of GLP-1 levels.","authors":"Çalık Başaran, Nursel; Dotan, Idit; Dicker, Dror","year":2025,"journal":"International journal of obesity (2005), 49(3), 412-417","doi":"10.1038/s41366-024-01461-2","pmid":"38225284","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14676","title":"Guideline for the Use of Natriuretic Peptides in the Early Diagnosis and Management of Heart Failure in Primary Care (Joint Consensus Report by the Eurasian Society of Heart Failure and the Turkish Association of Family Medicine).","authors":"Çelik, Ahmet; Öztürk, Güzin Zeren; Çavuşoğlu, Yüksel; Ardıç, Cüneyt; Nalbantgil, Sanem; Arıca, Seçil; Temizhan, Ahmet; Altay, Hakan; Yılmaz, Mehmet Birhan; Özsarı, Haluk; Ural, Dilek","year":2025,"journal":"Balkan medical journal, 42(2), 94-107","doi":"10.4274/balkanmedj.galenos.2025.2024-12-110","pmid":"40033605","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14677","title":"Paradigm shift in obesity treatment: an extensive review of current pipeline agents.","authors":"Çetin, Ecesu; Pedersen, Brian; Burak, Mehmet Furkan","year":2025,"journal":"Turkish journal of medical sciences, 55(1), 1-16","doi":"10.55730/1300-0144.5938","pmid":"40104296","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14678","title":"Lipopeptide-mediated delivery of CRISPR/Cas9 ribonucleoprotein complexes for gene editing and correction.","authors":"Öktem, Mert; Nguyen, Thai Hoang; Bosman, Esmeralda D C; Fens, Marcel H A M; Caiazzo, Massimiliano; Mastrobattista, Enrico; Lei, Zhiyong; de Jong, Olivier G","year":2025,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 383, 113854","doi":"10.1016/j.jconrel.2025.113854","pmid":"40389165","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14679","title":"Effects of mindfulness-based stress reduction on neuropeptide Y plasma levels in stressed individuals.","authors":"Østergaard, Helle Degnbol; Pallesen, Karen Johanne; Nielsen, Marit Nyholm; Fjorback, Lone; Juul, Lise; Winterdahl, Michael","year":2025,"journal":"Journal of psychiatric research, 181, 400-404","doi":"10.1016/j.jpsychires.2024.12.011","pmid":"39657564","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14680","title":"Variant screening of PYY3-36 leads to potent long-acting PYY analogs with superior Y2 receptor selectivity.","authors":"Østergaard, Søren; Jessen, Carsten; Paulsson, Johan F; Kasimova, Marina A; Conde-Frieboes, Kilian W; Straarup, Ellen Marie; Skyggebjerg, Rikke Bjerring; Ynddal, Lars; Sanfridson, Annika; Wulff, Birgitte S; Chambers, Adam P","year":2025,"journal":"Science translational medicine, 17(791), eadq6392","doi":"10.1126/scitranslmed.adq6392","pmid":"40138456","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Systematic variant screening of PYY3-36 identified key amino acids responsible for Y2 receptor selectivity, potency, and stability. Combined with fatty diacid derivatization (attaching a fatty acid chain for albumin binding and extended half-life), this produced highly selective, long-acting Y2 receptor agonists.\n\nIn preclinical models:\n- The analogs improved glucose metabolism in diabetic db/db mice\n- Combined with a long-acting GLP-1 receptor agonist, they showed superior blood glucose lowering in diabetic ZSF1 rats compared to GLP-1 alone\n- The combination also produced greater body weight loss than GLP-1 alone in a high-fat diet-induced mouse obesity model\n\nOne analog, PYY1875, has progressed into clinical trials for obesity, validating the drug development approach.","whyItMatters":"GLP-1 drugs like semaglutide have transformed obesity treatment, but there is strong interest in combining them with other gut hormones for even greater efficacy. PYY acts through different brain circuits than GLP-1, suppressing appetite through complementary mechanisms. A long-acting PYY analog that can be combined with existing GLP-1 drugs could represent the next generation of obesity treatments — and one candidate is already in human trials. This is the same multi-hormone approach that led to tirzepatide (GLP-1/GIP dual agonist).","specificNumbers":"","methodology":"The researchers performed systematic variant screening of PYY3-36, substituting amino acids at each position to identify residues critical for Y2 receptor selectivity, potency, and peptide stability. Lead candidates were modified with fatty diacid derivatization to extend half-life through albumin binding. Analogs were tested in vitro for Y1, Y2, Y4, and Y5 receptor activity. In vivo efficacy was assessed in diabetic db/db mice (glucose metabolism), diabetic ZSF1 rats (blood glucose lowering in combination with GLP-1 agonist), and high-fat diet-induced obese mice (body weight loss, alone and combined with GLP-1 agonist).","limitations":"All efficacy data is from animal models (db/db mice, ZSF1 rats, diet-induced obese mice), which may not fully predict human responses. The specific degree of improvement over GLP-1 alone is not quantified in the abstract. Clinical trial results for PYY1875 in humans are not yet available. The long-term safety profile of chronic Y2 receptor activation is unknown. Whether PYY analogs can match the dramatic weight loss seen with newer GLP-1 drugs in humans remains to be determined."},{"rthcId":"RPEP-14681","title":"Nanoliposomal Encapsulation and Purification of Angiotensin-Converting Enzyme Inhibitor Peptides from Ulva rigida.","authors":"Şensu, Eda; Koku, Harun; Demircan, Evren; Şişman, Sebahat; Gülseren, İbrahim; Karaduman, Tuğçe; Çakır, Bilal; Okudan, Emine Şükran; Duruksu, Gökhan; Özçelik, Beraat; Yücetepe, Aysun","year":2025,"journal":"ACS omega, 10(21), 21609-21620","doi":"10.1021/acsomega.5c00780","pmid":"40488009","tags":["cardiovascular","drug-delivery-systems","nutraceuticals-supplements"],"studyType":"laboratory study","evidenceStrength":"preliminary","keyFinding":"ACE-inhibitory peptides purified from green seaweed (Ulva rigida) and encapsulated in chitosan-coated nanoliposomes achieved 92% encapsulation efficiency and retained 37.5% of their blood pressure-lowering activity after encapsulation.","whyItMatters":"Natural peptides that lower blood pressure degrade quickly. Nanoliposome encapsulation could make them stable enough for use as functional food ingredients or supplements.","specificNumbers":"Ulva rigida hydrolyzed with pepsin then trypsin. Peptides <3 kDa showed strongest ACE inhibition. Identified by mass spectrometry and in silico analysis. Nanoliposome encapsulation efficiency: 92.0 ± 4.5%. ACE-inhibitory activity retained: 37.5% after encapsulation.","methodology":"Enzymatic hydrolysis of U. rigida protein, ultrafiltration by molecular weight, ion exchange chromatography, mass spectrometry and in silico peptide identification, nanoliposome formulation with chitosan coating, physical characterization (zeta potential, PDI, size, DSC, SEM, FT-IR), and ACE inhibition assay.","limitations":"In vitro only. Significant activity loss after encapsulation (62.5%). Oral bioavailability and in vivo antihypertensive effect not tested. Seaweed peptide yields may vary by batch."},{"rthcId":"RPEP-14682","title":"Small-Molecule GLP-1 Receptor Agonists: A Promising Pharmacological Approach.","authors":"Șeremet, Oana Cristina; Pușcașu, Ciprian; Andrei, Corina; Nițulescu, Georgiana; Zbârcea, Cristina Elena; Olaru, Octavian Tudorel","year":2025,"journal":"Medicina (Kaunas, Lithuania), 61(11)","doi":"10.3390/medicina61111902","pmid":"41303737","tags":["glp1-receptor-agonists","drug-discovery-screening"],"studyType":"narrative review","evidenceStrength":"not applicable (review)","keyFinding":"Small-molecule GLP-1R agonists are being developed as oral alternatives to injectable peptide-based GLP-1 drugs. They show promising efficacy for insulin secretion and weight loss in preclinical and early clinical studies.","whyItMatters":"Oral pills are easier and cheaper than injections. Small-molecule GLP-1R agonists could dramatically expand patient access and adherence to this drug class.","specificNumbers":"Not specified (review of preclinical and early clinical pipeline)","methodology":"Narrative review of pharmacodynamic profiles and clinical/preclinical progress of small-molecule GLP-1R agonists.","limitations":"Review of early-stage research. Most small-molecule candidates are preclinical or in early clinical trials. Long-term efficacy and safety data are lacking."},{"rthcId":"RPEP-14683","title":"Evaluating Suicidal Risk in GLP-1RA Therapy: An Umbrella Review of Meta-Analytic Evidence.","authors":"Ștefănescu, Cristina; Bratu, Elena Alexandra; Pelin, Ana Maria; Boroi, Denisa; Crecan-Suciu, Bianca Daniela; Ștefănescu, Victorița","year":2025,"journal":"Healthcare (Basel, Switzerland), 13(22)","doi":"10.3390/healthcare13222958","pmid":"41302345","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"No significant association between GLP-1RA therapy and suicidality across integrated meta-analytic evidence. Methodological limitations: heterogeneous definitions, inconsistent reporting, small event numbers. Ongoing surveillance recommended.","whyItMatters":"Suicidality concerns have threatened GLP-1 drug adoption. This highest-level evidence synthesis provides reassurance while appropriately acknowledging study limitations.","specificNumbers":"","methodology":"First umbrella review (review of meta-analyses) on GLP-1RA and suicidality. Systematic search of MedLine, PubMed, PsychInfo, Web of Science, Science Direct, Sage, Wiley, Springer.","limitations":"Umbrella reviews depend on quality of underlying meta-analyses. Suicidal events are rare and may be underreported. Post-marketing data may differ from trial data."},{"rthcId":"RPEP-14684","title":"Jaiswal 2026 Comprehensive Identification And Characterizationization","authors":"","year":2026,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14685","title":"Li 2026 Mechanismdriven Screening Of Membranetargeting","authors":"","year":2026,"journal":"","doi":null,"pmid":null,"tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14686","title":"EXPRESS: Assessment of Pain-Related Biomarkers in Migraine and Tension Headache Patients Pre- and Post-Botulinum Toxin Therapy.","authors":"Abbas, Afrah Abdulsahib; Aswad, Fawaz; Zaidan, Taghreed","year":2026,"journal":"Molecular pain, 17448069261422070","doi":"10.1177/17448069261422070","pmid":"41589664","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14687","title":"The association between glucagon-like peptide 1 receptor agonists therapy and outcomes after heart transplant.","authors":"Abbas, Mohammed Tiseer; Farina, Juan M; Ibrahim, Omar H; Ahmed, Sherif; Bismee, Nadera N; Awad, Kamal; Jamal, Fares; Sheashaa, Hesham; Pereyra Pietri, Milagros; Scalia, Isabel G; Baba Ali, Nima; Attaripour Esfahani, Sogol; Abdelfattah, Fatmaelzahraa E; Razaghi, Mahshad; Mahmoud, Ahmed K; Ibrahim, Ramzi; Steidley, D Eric; Rosenthal, Julie L; LeMond, Lisa M; Scott, Robert L; Hardaway, Brian W; Downey, Francis X; Sell-Dottin, Kristen A; Patel, Parag C; Clavell, Alfredo L; Ayoub, Chadi; Arsanjani, Reza","year":2026,"journal":"The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation","doi":"10.1016/j.healun.2026.01.003","pmid":"41520801","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14688","title":"Post-weight Loss Body Contouring Surgery: Complication Rates Following Bariatric Surgery, Injectable GLP-1 Pharmacotherapy, Combination Therapy, and Lifestyle Modification.","authors":"Abbott, Erin N; Giannas, Emmanuel; Dorjsuren, Nomongo; King, Daniella; Li, Ruoying; Christopher, Adrienne; Gergoudis, Franklin; Gabriel, Allen; Perdikis, Galen; Assi, Patrick","year":2026,"journal":"Aesthetic surgery journal","doi":"10.1093/asj/sjag049","pmid":"41742366","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 1,002 post-weight loss body contouring patients, complication rates did not differ significantly by weight loss method across all procedure types (panniculectomy, brachioplasty, thighplasty, breast surgery). Weight loss methods included bariatric surgery (67.9%), lifestyle modification (14.3%), combination therapy (10.1%), and GLP-1 pharmacotherapy alone (7.8%).\n\nBMI at the time of surgery and diabetes were identified as independent predictors of increased postoperative complications, regardless of how the weight was lost. Each procedure type showed its own expected complication patterns, but the method of weight loss was not a factor.","whyItMatters":"The explosion in GLP-1 medication use has driven a parallel surge in demand for body contouring surgery. Surgeons and patients have had little data on whether GLP-1-mediated weight loss carries different surgical risks compared to traditional methods. This study provides the first substantial evidence that the weight loss method doesn't matter — only the patient's condition at the time of surgery does.","specificNumbers":"","methodology":"This was a single-center, retrospective cohort study of patients who underwent post-weight loss body contouring surgery between January 2019 and December 2024. Eligible patients were adults who achieved weight loss and then had panniculectomy, brachioplasty, thighplasty, or breast surgery. Patients were classified into four groups by weight loss method. The primary outcome was the incidence of postoperative complications within 90 days for each procedure.","limitations":"Single-center retrospective study, which limits generalizability. Baseline characteristics differed significantly across weight loss groups, which may confound comparisons despite statistical adjustments. The GLP-1-only group was relatively small (7.8% of 1,002 = ~78 patients), limiting statistical power to detect differences. The study period (2019-2024) captures early GLP-1 adoption, and patients on newer high-dose regimens may differ. Complications were tracked for only 90 days, missing potential longer-term issues."},{"rthcId":"RPEP-14689","title":"Efficacy and safety of GLP-1 receptor agonists and SGLT2 inhibitors as adjuncts to insulin in type 1 diabetes: Systematic review and meta-analysis.","authors":"Abdel-Rahman, Sama M; Al-Shiab, Rama; Shah, Ermeena; Güldan, Mustafa; Ak, Ahmet Bahadır; Yilmaz, Zeynep Y; Fidan, Derya Göksu; Ozbek, Lasin; Kanbay, Mehmet","year":2026,"journal":"Diabetes, obesity & metabolism","doi":"10.1111/dom.70506","pmid":"41605813","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14690","title":"Semaglutide and the Risk of Non-Arteritic Ischemic Optic Neuropathy: A Systematic Review and Certainty of Evidence Meta-Analysis.","authors":"Abdelaal, Abdelaziz; Serhan, Hashem Abu; Alsaadi, Mustafa; Yaldo, Luke; Gaier, Eric D; Elhusseiny, Abdelrahman M","year":2026,"journal":"Ophthalmology","doi":"10.1016/j.ophtha.2026.02.013","pmid":"41692115","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across six observational studies with 4,831,654 patients, pooled odds ratios showed no statistically significant increase in NAION with semaglutide versus non-GLP-1 RA comparators (OR=2.44; 95% CI 0.59–10.15; very low certainty). When compared specifically to SGLT2 inhibitors, the pooled OR was 0.72 (95% CI 0.38–1.35).\n\nIn adjusted time-to-event analyses, the pooled hazard ratio was 1.63 (95% CI 0.88–2.39; low certainty), but this estimate was fragile — removing one influential study shifted it to 1.92 (95% CI 1.03–2.81). By indication, the signal differed: type 2 diabetes patients showed a pooled aHR of 1.70 (95% CI 1.10–2.64; low certainty), while obesity/overweight patients showed no increased risk (aHR 0.47; 95% CI 0.19–1.13; moderate certainty).","whyItMatters":"Semaglutide is one of the most widely prescribed drugs globally, and even rare side effects affect large numbers of people. NAION can cause permanent vision loss. Clarifying whether there is a genuine risk is critical for the millions of patients using semaglutide for diabetes or weight management, and for the clinicians counseling them about potential side effects.","specificNumbers":"","methodology":"This systematic review and meta-analysis followed PRISMA guidelines and was prospectively registered on PROSPERO. Researchers searched seven databases plus Google Scholar through August 2025 for studies comparing semaglutide users to non-GLP-1 RA users with NAION as an outcome. Six observational studies were included. Random-effects models pooled odds ratios and adjusted hazard ratios, with subgroup analyses by treatment indication. Evidence certainty was graded using the GRADE framework.","limitations":"All included studies were observational, preventing causal conclusions. There was substantial heterogeneity between studies (I² up to 99%). Evidence certainty ranged from very low to moderate by GRADE assessment. Residual confounding is likely since NAION risk factors overlap with conditions treated by semaglutide. The difference between diabetes and obesity indications may reflect underlying disease risk rather than a true drug-indication interaction. The results were fragile — sensitive to removal of a single study."},{"rthcId":"RPEP-14691","title":"Distinct impact of splenic denervation and the role of TRPV1 in LIPUS-induced anti-inflammatory milieu in the kidney: Involvement of neurochemicals, Nrf2/HO-1 modulation and change of macrophage phenotype.","authors":"Abdelwahed, Omaima Mohammed; Aboulhoda, Basma Emad; Gouda, Sarah Ali Abdelhameed; Shoukry, Tarek; Rashed, Laila; Alkaffas, Marwa; Abdelhady, Ebtehal Gamal; Alghamdi, Mansour A; Abdalla, Hend; Sharawy, Nivin","year":2026,"journal":"Tissue & cell, 100, 103376","doi":"10.1016/j.tice.2026.103376","pmid":"41690069","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14692","title":"Recent advances in dendritic cell-derived exosomes in cancer and cancer stem cell therapy.","authors":"Abdul Kareem, Radhwan; Naji Sameer, Hayder; Athab, Zainab H; Adil, Mohaned; Yaseen, Ahmed; Allela, Omer Qutaiba B","year":2026,"journal":"International reviews of immunology, 1-33","doi":"10.1080/08830185.2026.2614776","pmid":"41532483","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14693","title":"Tirzepatide and Cardiovascular Outcomes: A Narrative Review of Mechanisms, Efficacy and Implications for Heart Failure Management.","authors":"Abdul-Hafez, Hamza A; Awashra, Ameer; Bdir, Sosana; Saife, Sarah; Salah, Qasem; Barbarawi, Mohammed; Swaileh, Thabet; Emara, Ahmed; Elgendy, Mohamed S; Shubietah, Abdalhakim","year":2026,"journal":"Endocrinology, diabetes & metabolism, 9(1), e70152","doi":"10.1002/edm2.70152","pmid":"41566974","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14694","title":"Liraglutide attenuates aluminum chloride-induced Alzheimer's disease in rats by modulating the oxLDL/LPA/LPAR1 pathway.","authors":"Abo El-Magd, Nada F; Ramadan, Nehal M; Eraky, Salma M","year":2026,"journal":"Communications biology, 9(1), 262","doi":"10.1038/s42003-026-09531-z","pmid":"41673096","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In aluminum chloride-induced Alzheimer's model rats, liraglutide (0.3 mg/kg twice daily, subcutaneous) significantly ameliorated anxiety, depression-like behaviors, and memory function deficits compared to untreated aluminum-exposed rats.\n\nLiraglutide therapy preserved brain histopathological structure and demonstrated antioxidant and anti-apoptotic properties. Most notably, liraglutide decreased hippocampal levels of oxidized LDL (oxLDL), lysophosphatidic acid (LPA), LPA receptor 1 (LPAR1), and β-secretase 1 (BACE1) compared to the aluminum chloride group. This oxLDL/LPA/LPAR1/BACE1 pathway represents a novel mechanism for liraglutide's neuroprotective effects, reported for the first time in this study.","whyItMatters":"Finding new mechanisms by which GLP-1 drugs protect the brain is critical as several clinical trials are testing these medications for Alzheimer's disease. The identification of the oxLDL/LPA/LPAR1/BACE1 pathway is significant because it connects lipid metabolism (oxidized LDL) to amyloid production (BACE1) — a link that could be targeted therapeutically. If liraglutide can reduce BACE1 activity through this pathway, it addresses one of the fundamental processes driving Alzheimer's disease.","specificNumbers":"","methodology":"Male Wistar rats were divided into four groups: normal control, aluminum chloride only (70 mg/kg daily intraperitoneal for 45 days), aluminum chloride + liraglutide (0.3 mg/kg twice daily subcutaneous), and aluminum chloride + donepezil (1 mg/kg daily intraperitoneal, as positive control). Behavioral testing assessed anxiety, depression, and memory. Histopathological examination evaluated brain structure. Molecular assays measured hippocampal levels of oxidative stress markers, apoptotic markers, oxLDL, LPA, LPAR1, and BACE1.","limitations":"The aluminum chloride model of Alzheimer's disease is a chemical induction model that does not fully replicate human Alzheimer's pathology (which involves tau tangles, genetic risk factors, and decades of progression). Specific group sizes were not stated in the abstract. The pathway analysis is correlative — demonstrating that liraglutide reduces these markers does not definitively prove the causal chain. The subcutaneous liraglutide dose (0.3 mg/kg twice daily) may not reflect human brain exposure. Translation from rats to humans is uncertain."},{"rthcId":"RPEP-14695","title":"Treatment with radionuclide-labeled peptides in refractory meningiomas: Updated review and clinical perspectives.","authors":"Abou Jokh Casas, E; Vercher Conejero, J L; Repetto, A; Bello Arques, P; Cambil Molina, T; Rodriguez Gasén, A; Vallejo Casas, J A","year":2026,"journal":"Revista espanola de medicina nuclear e imagen molecular, 45(1), 500218","doi":"10.1016/j.remnie.2025.500218","pmid":"40915497","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14696","title":"Assessment of community awareness and attitude about the use of GLP 1 agonists as a treatment for obesity in Saudi Arabia: Cross-sectional study.","authors":"Abualhommos, Amal Khaleel; Al Hawaj, Maitham Abdullah; Alrasheed, Sharifa Yousef; Alessa, Reem Abdulrahman; Alhussain, Alzahra Yousef; Alabdulkareem, Rouaa Adel; Abdulaziz Alzamil, Raghad Ibrahim","year":2026,"journal":"Medicine, 105(2), e46957","doi":"10.1097/MD.0000000000046957","pmid":"41517730","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14697","title":"Development of a Follow-Up Protocol for Patients Treated with Injectable Semaglutide for Weight Loss: Design of a Research Study in Community Pharmacy.","authors":"Acuña Elvira, N","year":2026,"journal":"Farmaceuticos comunitarios, 18(1), 13-22","doi":"10.33620/FC.2173-9218.(2026).03","pmid":"41540992","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14698","title":"Trends in Use of Obesity Medications and Metabolic and Bariatric Surgery Among All of Us Participants From 2003 to 2023.","authors":"Adekunle, Olajide A; Le, Phuc; Boyer, Christopher; Gasoyan, Hamlet; Gupta, Dev Yash; Tran, Ha T; Yue, Yihua; Rothberg, Michael B","year":2026,"journal":"Obesity (Silver Spring, Md.)","doi":"10.1002/oby.70151","pmid":"41741949","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14699","title":"Unmasking the risk: euglycemic diabetic ketoacidosis induced by GLP-1 agonist in type 2 diabetes.","authors":"Adrejiya, Parth; Alhujaily, Ensaf; Abubaker, Mohammad; Dorenbush, Chelsae; Khouzam, Rami","year":2026,"journal":"Proceedings (Baylor University. Medical Center), 39(1), 163-165","doi":"10.1080/08998280.2025.2555778","pmid":"41487555","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A 59-year-old woman with type 2 diabetes and gastroparesis developed EDKA after initiating dulaglutide:\n\n- She had discontinued SGLT-2 inhibitors one month before the event\n- EDKA developed shortly after starting dulaglutide\n- Presentation: nausea, vomiting, abdominal pain, modestly elevated glucose\n- Laboratory findings confirmed EDKA (metabolic acidosis with ketones despite near-normal blood sugar)\n- Successfully treated with intravenous insulin and fluid resuscitation\n- Dulaglutide was discontinued, with no recurrence on follow-up\n\nThis case challenges the assumption that EDKA is primarily an SGLT-2 inhibitor complication and suggests GLP-1 RAs can trigger it in susceptible patients.","whyItMatters":"As millions of people start GLP-1 drugs for diabetes and weight loss, awareness of rare but serious complications is essential. EDKA is particularly dangerous because standard blood sugar monitoring won't catch it — glucose levels are only modestly elevated. The combination of gastroparesis (which can reduce food intake and cause vomiting) with a GLP-1 drug (which further suppresses appetite) may create metabolic conditions favoring ketone production. Clinicians need to be alert to this possibility.","specificNumbers":"","methodology":"This is a single case report describing the clinical presentation, laboratory findings, treatment, and outcome of a patient who developed euglycemic DKA after initiating dulaglutide therapy.","limitations":"This is a single case report, which is the weakest level of clinical evidence. The patient had recently discontinued SGLT-2 inhibitors, raising the possibility that residual effects of the prior medication contributed to the EDKA. The temporal association with dulaglutide initiation does not definitively prove causation. Gastroparesis itself can cause nausea and reduced food intake, which could independently contribute to ketosis. No mechanistic explanation for how dulaglutide specifically triggered EDKA is provided."},{"rthcId":"RPEP-14700","title":"Exceptional Response to Rechallenge Peptide Receptor Radionuclide Therapy in Metastatic Carotid Body Tumor.","authors":"Aggarwal, Piyush; Satapathy, Swayamjeet; Sarungbam, Bidya; Sood, Ashwani; Kumar, Rajender; Goyal, Shikha; Mittal, Bhagwant Rai","year":2026,"journal":"Clinical nuclear medicine, 51(1), e52-e54","doi":"10.1097/RLU.0000000000005930","pmid":"40310021","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A 45-year-old woman with metastatic carotid body tumor showed an excellent initial response to 177Lu-DOTATATE peptide receptor radionuclide therapy (PRRT). After disease progression with widespread metastases and spinal cord compression at multiple levels leaving her wheelchair-bound, rechallenge PRRT again produced an exceptional treatment response. This case demonstrates that retreatment with peptide-targeted radiation can be effective in somatostatin receptor-expressing paragangliomas.","whyItMatters":"Metastatic head and neck paragangliomas have very limited treatment options. This case demonstrates that peptide receptor radionuclide therapy — which specifically targets tumor cells using a somatostatin peptide analogue carrying a radioactive payload — can work not just once but twice in the same patient. This is important for clinicians managing these rare tumors who need to know that retreatment is a viable option.","specificNumbers":"","methodology":"This is a clinical case report of a single patient treated at a medical center. The patient was evaluated with imaging showing somatostatin receptor-expressing metastatic lesions, treated with 177Lu-DOTATATE PRRT initially with good response, then retreated upon disease recurrence. Treatment response was assessed clinically and with imaging.","limitations":"This is a single case report, representing the lowest level of clinical evidence. Individual responses cannot be generalized to all patients with metastatic paragangliomas. Long-term outcomes, cumulative radiation safety, and specific imaging response details are not provided in the abstract. The rarity of metastatic carotid body tumors makes it difficult to study systematically."},{"rthcId":"RPEP-14701","title":"Cardiovascular burden of long coronavirus disease: Clinical challenges and emerging biomarkers.","authors":"Aguiar, Carlos Eduardo Oliveira; Costa, Juan Marcos Caram; Oliveira, Marina Maria Gomes Leite; Lopes, Caio Ferraz; Lima, Pedro Henrique Melo; Dietrich, Victoria Cenci; Grenfell, Rafaella Fortini Queiroz; de Melo, Fabrício Freire","year":2026,"journal":"World journal of cardiology, 18(1), 112466","doi":"10.4330/wjc.v18.i1.112466","pmid":"41607619","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review categorizes long COVID cardiovascular biomarkers into established and emerging groups. Established markers include cardiac troponins (heart muscle damage), natriuretic peptides BNP/NT-proBNP (heart stress and failure), D-dimer (clotting), and inflammatory markers like C-reactive protein and interleukin-6.\n\nEmerging biomarkers with clinical potential include growth differentiation factor-15 (GDF-15, a stress-responsive peptide), galectin-3 (fibrosis and inflammation), von Willebrand factor (endothelial damage), endothelin-1 (a vasoconstrictor peptide indicating vascular dysfunction), and circulating microRNAs. The review emphasizes that no single biomarker is sufficient — combinations and longitudinal monitoring will be needed for effective clinical use in long COVID cardiovascular management.","whyItMatters":"Millions of people worldwide have long COVID, and cardiovascular complications are among the most dangerous. Many patients have subtle heart damage that standard exams miss. Peptide biomarkers like BNP and endothelin-1 can detect this damage through a simple blood test, potentially allowing early intervention before heart failure or other serious complications develop. Better biomarker strategies could personalize follow-up care for the millions of long COVID patients.","specificNumbers":"","methodology":"This is a narrative review article that synthesizes the current literature on cardiovascular manifestations of long COVID and the biomarkers used for diagnosis, risk stratification, and therapy monitoring. The authors reviewed both established cardiac biomarkers with proven clinical utility and emerging candidates with preliminary evidence in the long COVID context.","limitations":"As a narrative review, this paper does not perform meta-analysis or systematic evidence grading. Many of the emerging biomarkers lack large-scale validation studies specific to long COVID. There is no standardization in biomarker testing protocols across studies, making direct comparisons difficult. The review acknowledges the absence of validated longitudinal predictive models for cardiovascular outcomes in long COVID."},{"rthcId":"RPEP-14702","title":"Growth Hormone and IGF-1 Actions in the Brain and Neuropsychiatric Diseases.","authors":"Aguiar-Oliveira, Manuel H; Boguszewski, Margaret C S; Rovaris, Diego L; Donato, Jose","year":2026,"journal":"Physiology (Bethesda, Md.), 41(1), 0","doi":"10.1152/physiol.00009.2025","pmid":"40623083","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14703","title":"Host Defense Antimicrobial Peptides (HDPs) as Regulators of Hemostasis and Vascular Biology.","authors":"Aguilar-Ruiz, Sergio Roberto; Sánchez-Peña, Francisco Javier; Rodríguez-Magadán, Héctor Maximino; Domínguez-Martínez, Miguel Angel; Bernardino-Hernández, Héctor Ulises; Aquino-Domínguez, Alba Soledad","year":2026,"journal":"Biomolecules, 16(2)","doi":"10.3390/biom16020220","pmid":"41750290","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies several key mechanisms:\n\n1. Platelets and megakaryocytes are active synthesizers of host defense peptides, not passive carriers — representing a paradigm shift in understanding platelet biology.\n\n2. Different peptides have distinct effects: LL-37 activates platelets via the glycoprotein VI (GPVI) receptor, while defensins stabilize fibrin clots through amyloid-like interactions.\n\n3. HDPs function as concentration-dependent molecular switches — at lower levels they promote physiological repair, while at higher levels (during infection) they can drive pathological thromboinflammation.\n\n4. The review proposes \"adaptive thrombopoiesis\" — a concept where systemic peptide surges during infection act as danger signals that reprogram newly formed platelets for enhanced immune function.","whyItMatters":"The connection between infection and blood clotting complications (thromboinflammation) has been dramatically highlighted by conditions like COVID-19. Understanding that antimicrobial peptides serve as molecular switches between repair and pathological clotting could explain why infections sometimes trigger dangerous cardiovascular events — and open new therapeutic avenues.","specificNumbers":"","methodology":"This is a critical narrative review synthesizing current literature on host defense peptides' roles in hemostasis, platelet biology, endothelial cell interactions, and tissue repair. The authors integrated molecular mechanism studies, functional assays, and emerging concepts to propose new frameworks for understanding peptide-mediated vascular regulation.","limitations":"As a review article, this study synthesizes but does not generate new experimental data. Many of the proposed frameworks (concentration-dependent switching, adaptive thrombopoiesis) are hypotheses that require further experimental validation. The therapeutic potential of peptidomimetics discussed remains largely theoretical at this stage."},{"rthcId":"RPEP-14704","title":"Design of Experiments (DoE)-Optimized Polymeric Oxytocin Nanoparticles for Enhanced Nose-to-Brain Delivery.","authors":"Ahmad, Naveed; Han, Shunping; Utami, Rifka; Baker, Rafal; Helal, Dina; Li, Zhuoni; Tricklebank, Mark; Paloyelis, Yannis; Wang, Julie; Petrinovic, Marija M; Bansal, Sukhi; Al-Jamal, Khuloud T","year":2026,"journal":"Small (Weinheim an der Bergstrasse, Germany), 22(8), e11603","doi":"10.1002/smll.202511603","pmid":"41416478","tags":[],"studyType":"animal-study","evidenceStrength":"low","keyFinding":"Researchers created PEGylated PLGA nanoparticles loaded with oxytocin (OT-NP-PEG) that successfully delivered the peptide from the nose directly to the brain in mice. The nanoparticles were 93–116 nm in diameter with sustained release (>42% at 24 hours, 58% at 72 hours) and showed greater diffusion through simulated nasal mucus than non-PEGylated versions.\n\nUsing radioactively labeled oxytocin ([14C] OT), the team demonstrated rapid brain uptake — particularly in the olfactory bulb and frontal cortex — with reduced accumulation in the blood and liver compared to free oxytocin. Mice treated with intranasal OT-NP-PEG showed increased self-grooming, confirming the oxytocin remained biologically active after delivery.","whyItMatters":"Oxytocin is being explored as a treatment for autism spectrum disorder, but nasal sprays deliver it inconsistently to the brain, with much of the peptide ending up in the bloodstream instead. This nanoparticle system could solve that problem by protecting oxytocin and routing it directly through the nose-to-brain pathway, potentially making oxytocin therapy more effective and reducing side effects.","specificNumbers":"Particle size: 93–116 nm · Drug loading: 2.8–3.5% w/w · Release: >42% at 24h, 58% at 72h · Zeta potential: -21 to -33 mV · [14C] OT synthesis: 74% chemical yield, 53% radiochemical yield","methodology":"Researchers used a Design of Experiments (DoE) statistical approach to optimize PLGA nanoparticle formulations loaded with oxytocin. They created both standard (OT-NP) and PEGylated (OT-NP-PEG) versions, characterizing particle size, stability, and release kinetics. They synthesized radioactively labeled [14C] oxytocin to track biodistribution after intranasal administration in mice, measuring uptake in the brain (olfactory bulb, frontal cortex), blood, and liver. Behavioral effects were assessed by measuring self-grooming frequency.","limitations":"This is a preclinical mouse study — nose-to-brain delivery may differ significantly in humans due to anatomical differences. The behavioral endpoint (self-grooming) is a crude proxy for the social behavior effects sought in ASD treatment. No toxicity data or long-term safety assessment is reported. The transition from mice to human clinical use involves substantial formulation and regulatory hurdles."},{"rthcId":"RPEP-14705","title":"Early glucagon-like peptide-1 receptor agonist use after myocardial infarction in patients with type 2 diabetes.","authors":"Ahmad, Omar; Ibrahim, Ramzi; Pham, Hoang Nhat; Abdelnabi, Mahmoud; Elbenawi, Hossam; Salih, Mohammed; Farina, Juan; Bhakta, Mayurkumar D; Sell-Dottin, Kristen A; Yang, Eric H; Sweeney, John P; Fortuin, F David; Simper, David; Al-Kindi, Sadeer; Lee, Kwan; Nasir, Khurram; Ayoub, Chadi; Arsanjani, Reza","year":2026,"journal":"International journal of cardiology, 445, 134042","doi":"10.1016/j.ijcard.2025.134042","pmid":"41297711","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14706","title":"Discovery proteomics to detect salivary biomarkers in dog and human periodontitis: Mass spectrometry-based analysis.","authors":"Ahmad, Paras; Lowe, Candace; Chumala, Paulos; Siqueira, Walter L","year":2026,"journal":"Veterinary journal (London, England : 1997), 315, 106521","doi":"10.1016/j.tvjl.2025.106521","pmid":"41319894","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14707","title":"Metal Ion-Specific Modulation of Network Connectivity and Defects in Poly(ethylene glycol)-Peptide Conjugate Assemblies and Hydrogels.","authors":"Ahmadi, Mostafa; Wittek, Kamila; Rieger, Hanna Sophie; Thomas, Marius; Hartmann, Lars; Besenius, Pol; Seiffert, Sebastian","year":2026,"journal":"Chemistry of materials : a publication of the American Chemical Society, 38(3), 1240-1252","doi":"10.1021/acs.chemmater.5c02542","pmid":"41696507","tags":["peptide-hydrogels","biomaterials"],"studyType":"laboratory-study","evidenceStrength":"moderate","keyFinding":"Researchers created hydrogels from peptide-polymer conjugates — short phenylalanine-histidine peptides linked to polyethylene glycol (PEG) chains. These conjugates self-assemble into beta-sheet nanofibers at acidic pH, forming cross-links that hold the hydrogel together.\n\nAdding metal ions (cobalt, nickel, copper, or zinc) dramatically improved the hydrogel's mechanical properties. Metal coordination produced orders-of-magnitude higher network stability, expanded the range of stress the gel could withstand without breaking, and improved the gel's ability to recover after deformation. Each metal ion produced different effects depending on its coordination geometry, giving researchers a tunable toolkit for engineering gel properties.\n\nThe assembly was enthalpy-driven at low concentrations, but at high concentrations, chain stretching created an entropic penalty that limited network connectivity.","whyItMatters":"Peptide-based hydrogels are promising materials for drug delivery, wound healing, and tissue engineering — but fine-tuning their mechanical properties has been challenging. This study shows that simply adding different metal ions can dramatically change how strong, stable, and responsive the gel is, without redesigning the peptide itself. This gives biomaterial engineers a simple dial to turn when designing gels for specific medical applications.","specificNumbers":"4 metal ions tested (Co²⁺, Ni²⁺, Cu²⁺, Zn²⁺) · Orders-of-magnitude improvement in network stability · 5-amino-acid peptide units · PEG-peptide conjugate platform","methodology":"Laboratory study using circular dichroism spectroscopy to characterize peptide secondary structure and self-assembly, and rheological measurements to assess hydrogel mechanical properties (network stability, linear viscoelastic region, recovery behavior). Four different divalent metal ions were tested for their effects on gel structure and dynamics.","limitations":"This is a materials science study conducted entirely in vitro — no biological testing was performed. The translation of these tunable hydrogel properties to actual biomedical applications (drug delivery, wound healing) remains to be demonstrated. Biocompatibility of the metal-ion-containing gels is not addressed."},{"rthcId":"RPEP-14708","title":"GLP-1 receptor agonists for smoking cessation: a narrative review of weight management potential.","authors":"Ahmed, Ghazi Uddin; Zehra, Eiman; Rasheed, Sana; Akhtar, Syed Owais; Raza, Ahmed Asad; Mujaddadi, Khunsha; Samadi, Abedin","year":2026,"journal":"Annals of medicine and surgery (2012), 88(3), 2373-2382","doi":"10.1097/MS9.0000000000004725","pmid":"41789246","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review synthesizes preclinical and limited clinical evidence showing that GLP-1 receptor agonists may address nicotine dependence through two mechanisms:\n\n1. **Reduced nicotine cravings**: GLP-1 RAs modulate central reward pathways (mesolimbic dopamine system) that underlie nicotine's addictive properties, potentially reducing cravings and nicotine intake.\n2. **Weight gain prevention**: The well-established appetite-suppressing and weight-loss effects of GLP-1 RAs could counteract the metabolic changes that follow nicotine withdrawal (increased caloric intake, reduced energy expenditure).\n\nThis dual mechanism could improve quit success rates while eliminating one of the primary psychological barriers to smoking cessation.","whyItMatters":"Smoking kills over 8 million people annually, and weight gain after quitting is both a health risk and a major deterrent to quitting. If GLP-1 agonists — already prescribed to millions for weight loss — can simultaneously address nicotine addiction, it could revolutionize smoking cessation and prevent relapse in a population that has been underserved by existing quit-smoking medications.","specificNumbers":"","methodology":"This is a narrative review synthesizing evidence from preclinical animal studies, limited clinical trials, and pharmacological literature on GLP-1 receptor agonists' effects on nicotine dependence and post-cessation weight management.","limitations":"The human evidence base is very limited: small sample sizes, short follow-up periods, and reliance on preliminary or observational data. No large randomized controlled trials specifically testing GLP-1 RAs for smoking cessation have been completed. Potential side effects (nausea, pancreatitis risk) and the cost of GLP-1 drugs could limit real-world applicability. The narrative review format does not systematically assess study quality or risk of bias."},{"rthcId":"RPEP-14709","title":"Efficacy of glucagon-like peptide-1 receptor agonists in idiopathic intracranial hypertension: A systematic review and meta-analysis.","authors":"Ahmed, Warda; Gandhi, Om H; Yu, Nathan; Brant, Jason; Hwa, Tiffany; Bagley, Linda; Tamhankar, Madhura; Feroze, Abdullah; Choudhri, Omar","year":2026,"journal":"Journal of the neurological sciences, 480, 125711","doi":"10.1016/j.jns.2025.125711","pmid":"41468715","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14710","title":"Bowel preparation quality in patients using glucagon-like peptide-1 agonists: a systematic review and meta-analysis.","authors":"Ahmed, Zohaib; Iqbal, Amna; Arif, Syeda Faiza; Campbell, Connor; Fehlman, Jared; Allen, David James; Lee Smith, Wade; Khalil, Basmah; Kamal, Faisal; Iqbal, Umair; Nawras, Ali; Alastal, Yaseen; Adler, Douglas G","year":2026,"journal":"Gastrointestinal endoscopy, 103(2), 235-240.e5","doi":"10.1016/j.gie.2025.08.027","pmid":"40846241","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14711","title":"Glucagon-like Peptide-1 Receptor Agonist Use and Risk of Cataract Development.","authors":"Ahuja, Abhimanyu S; Paredes, Alfredo A; Ahuja, Sejal A; Young, Benjamin K","year":2026,"journal":"American journal of ophthalmology, 281, 666-673","doi":"10.1016/j.ajo.2025.10.021","pmid":"41130371","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14712","title":"Glucagon-like Peptide-1 Receptor Agonist Use and Pancreatic Cancer Risk in Patients with Chronic Pancreatitis.","authors":"Ailawadi, Sarina; Murphy, Jennifer E; Storandt, Michael H; Mahipal, Amit","year":2026,"journal":"Cancers, 18(2)","doi":"10.3390/cancers18020179","pmid":"41595103","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14713","title":"Pharmacological intervention: Challenges and promising outcomes for fat loss and preservation of lean body mass in the treatment of overweight and type 2 diabetes.","authors":"Aimelet, Viktor; Holst, Jens Juul","year":2026,"journal":"Diabetes, obesity & metabolism, 28(2), 803-816","doi":"10.1111/dom.70229","pmid":"41178728","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14714","title":"Clinical Trial: Semaglutide Versus Placebo in NIT-Assessed MASH-A Multicenter Randomised Placebo-Controlled Trial (SAMARA).","authors":"Ajmera, Veeral; Vuppalanchi, Raj; Khalili, Mandana; Sheikh, Muhammad Y; Risser, Joseph; Klein, Samuel; Tincopa, Monica; Madamba, Egbert; Singh, Seema; Siddiqi, Harris; Cortez-Moreno, Diana; Contrano, Darryl; Hofflich, Heather; Abeles, Ruth; Lunde, Ottar; Grunvald, Eduardo; Bettencourt, Ricki; He, Feng; Jain, Sonia; Richards, Lisa; Loomba, Rohit","year":2026,"journal":"Alimentary pharmacology & therapeutics","doi":"10.1111/apt.70516","pmid":"41527269","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14715","title":"Combating Bacterial Infections with Vitamin D-Induced Antimicrobial Peptides.","authors":"Akimbekov, Nuraly S; Digel, Ilya; Tastambek, Kuanysh; Rodriguez-Raecke, Rea; Tepecik, Atakan; Kistaubayeva, Aida S; Zha, Jian; Razzaque, Mohammed S","year":2026,"journal":"Advances in experimental medicine and biology, 1493, 13-31","doi":"10.1007/978-3-032-04357-3_3","pmid":"41219596","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14716","title":"Vitamin D-Induced Antimicrobial Peptides in Combating Viral Infections.","authors":"Akimbekov, Nuraly S; Digel, Ilya; Tastambek, Kuanysh; Rodriguez-Raecke, Rea; Kistaubayeva, Aida S; Sakhanova, Svetlana K; Wu, Xia; Razzaque, Mohammed S","year":2026,"journal":"Advances in experimental medicine and biology, 1493, 141-155","doi":"10.1007/978-3-032-04357-3_12","pmid":"41219605","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review presents evidence that vitamin D stimulates the production of antimicrobial peptides (AMPs) across multiple cell types involved in viral defense:\n\n- Natural killer cells, monocytes, neutrophils, and respiratory tract epithelial cells all produce AMPs in response to vitamin D signaling\n- These AMPs exhibit broad-spectrum activity against viruses, bacteria, and fungi\n- Beyond direct antimicrobial activity, AMPs serve as chemotactic agents (attracting immune cells) and promote cytokine and chemokine production (amplifying the immune response)\n- AMPs are evolutionarily conserved and part of the innate immune system, making them effective against both known and novel pathogens\n- Vitamin D appears to reduce viral survival and replication specifically through AMP induction","whyItMatters":"Drug-resistant infections are a global health emergency, and new antiviral approaches are urgently needed. Antimicrobial peptides represent the body's first line of defense — millions of years of evolution have optimized them against pathogens. Understanding how vitamin D regulates these peptides could lead to simple, accessible interventions (vitamin D supplementation) that boost natural antiviral immunity, particularly in populations with widespread vitamin D deficiency.","specificNumbers":"","methodology":"This is a book chapter reviewing the current evidence on vitamin D's immunomodulatory effects, focusing specifically on its role in inducing antimicrobial peptide production and the antiviral functions of these peptides. The review synthesizes research from in vitro studies, in vivo models, and clinical observations.","limitations":"As a review chapter, this does not present original experimental data. The evidence linking vitamin D supplementation to clinically meaningful reductions in viral infections is mixed, with some large clinical trials showing modest benefits and others showing none. The abstract does not discuss specific AMPs (like cathelicidin or defensins) or the optimal vitamin D levels needed for AMP induction. Most mechanistic evidence comes from in vitro studies, and translating AMP induction into clinical protection against viral disease has proven challenging."},{"rthcId":"RPEP-14717","title":"Discovery, Isolation, and Bactericidal Activity of a Cyclotide from Spigelia anthelmia L. (Loganiaceae).","authors":"Akinleye, Toluwanimi E; Sidiq, Latifat O; Attah, Alfred; Hellinger, Roland; Pabi, Lisa; Malanovic, Nermina; Ogbole, Omonike O; Gruber, Christian W","year":2026,"journal":"Journal of natural products, 89(1), 139-150","doi":"10.1021/acs.jnatprod.5c01216","pmid":"41524414","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14718","title":"Normal delivery following use of galcanezumab until the first and second trimesters of pregnancy: A report of 2 cases.","authors":"Akiyama, Hisanao; Yamano, Yoshihisa","year":2026,"journal":"Medicine, 105(9), e47895","doi":"10.1097/MD.0000000000047895","pmid":"41760025","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14719","title":"Antimicrobial peptides and proteins as rheostats of intestinal homeostasis and immunity.","authors":"Akoh-Arrey, Talia; Brooks, John F","year":2026,"journal":"Current opinion in immunology, 99, 102738","doi":"10.1016/j.coi.2026.102738","pmid":"41707585","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14720","title":"Estimating the excess expenditures associated with glucagon-like peptide-1 receptor agonist use among adults with diabetes in the United States.","authors":"Akpan, Nsima; Zhou, Bo; Rasu, Rafia S; Sambamoorthi, Usha","year":2026,"journal":"Journal of managed care & specialty pharmacy, 32(1), 14-26","doi":"10.18553/jmcp.2026.32.1.14","pmid":"41439383","tags":["glp-1-agonists","health-economics"],"studyType":"cross-sectional","evidenceStrength":"moderate","keyFinding":"GLP-1 receptor agonist users with diabetes had significantly higher total healthcare expenditures ($22,029) compared to non-users ($15,165). Use of GLP-1 RAs increased from 4.3% in 2016 to 10.6% in 2020 — roughly 1 in 13 adults with diabetes.\n\nAfter adjusting for age, sex, race, obesity, physical activity, and other conditions, GLP-1 RA use was independently associated with significantly higher total, payer, and out-of-pocket expenditures (all p ≤ 0.001). The economic burden fell on both insurance systems and patients themselves.","whyItMatters":"GLP-1 drugs like semaglutide and liraglutide have proven clinical benefits — better blood sugar control, weight loss, cardiovascular protection. But this study quantifies the other side of the equation: the financial cost. With usage more than doubling in just four years and total spending nearly $7,000 higher per user annually, the economic sustainability of widespread GLP-1 prescribing is a real concern for healthcare systems, insurers, and patients paying out-of-pocket.","specificNumbers":"n=7,670 (representing ~28.6 million US adults with diabetes) · 7.5% overall GLP-1 RA use · 4.3% in 2016 → 10.6% in 2020 · $22,029 vs $15,165 total expenditures (users vs non-users) · all expenditure differences p ≤ 0.001","methodology":"A cross-sectional analysis using the Medical Expenditure Panel Survey (MEPS), a nationally representative US dataset. Researchers identified 7,670 adults with diabetes across 2016, 2018, and 2020, compared healthcare spending between GLP-1 RA users and non-users, and used statistical models adjusted for demographics, social determinants, obesity, physical activity, and comorbidities to estimate excess expenditures.","limitations":"Cross-sectional design captures spending at a point in time, not long-term cost trajectories. MEPS data may not capture all indirect costs or newer GLP-1 drugs that entered the market after 2020. The study doesn't account for potential cost savings from reduced complications (e.g., fewer hospitalizations from better diabetes control). Some expenditure data in the abstract appears truncated."},{"rthcId":"RPEP-14721","title":"A plant-derived antimicrobial peptide with multiple mechanisms of action exhibiting antibacterial and antibiofilm activities comparable to or superior to polymyxin B.","authors":"Al Bouni, Mohamad Anas; Lima, Rui M; Jenei, Sándor; Tiricz, Hilda; Tímár, Edit; Domonkos, Ildikó; Kondorosi, Éva; Endre, Gabriella","year":2026,"journal":"Current research in microbial sciences, 10, 100535","doi":"10.1016/j.crmicr.2025.100535","pmid":"41551581","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14722","title":"Comparative Clinical and Metabolic Outcomes of GLP-1 Receptor Agonists Versus SGLT2 Inhibitors in Type 1 Diabetes: A Retrospective Cohort Study from Saudi Arabia.","authors":"Al Hayek, Ayman; Robert, Asirvatham Alwin; Al Burayk, Abdullah Khalid; Alwadai, Abdulrhman Nasser; Almutairi, Asma Mutni; Shabani, Abdullah Ali; Al Dawish, Mohamed Abdulaziz","year":2026,"journal":"Current diabetes reviews","doi":"10.2174/0115733998428827251223081042","pmid":"41691684","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14723","title":"Combining glucagon-like peptide 1 analogues with sodium-glucose cotransporter 2 inhibitors to treat patients with type 1 diabetes, BMI > 25 kg/m2, and chronic kidney disease - A randomised, controlled pilot study.","authors":"Al Ozairi, Ebaa; Taghadom, Etab; Irshad, Mohammad; Yousef, Anas Al; AlKandari, Jumana; Al-Najim, Werd; Alabdulkader, Shahd; Miras, Alexander D; le Roux, Carel W","year":2026,"journal":"Diabetes research and clinical practice, 231, 113066","doi":"10.1016/j.diabres.2025.113066","pmid":"41435968","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14724","title":"Weight loss in people with type 1 diabetes over 12 months: Real-world data comparing tirzepatide, semaglutide and liraglutide.","authors":"Al Ozairi, Ebaa; Irshad, Mohammad; Alkandari, Jumana; Sojan, Litty; Alroudhan, Dherar; Alotaibi, Nourah; le Roux, Carel W","year":2026,"journal":"Diabetes, obesity & metabolism, 28(1), 166-173","doi":"10.1111/dom.70172","pmid":"41048008","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14725","title":"Exploring the Therapeutic Potential of Sodium-Glucose Cotransporter-2 Inhibitors and Glucagon-Like Peptide-1 Receptor Agonists in Metabolic Dysfunction-Associated Steatotic Liver Disease and Metabolic Dysfunction-Associated Steatohepatitis in Patients with Type 2 Diabetes: A Narrative Review.","authors":"Al Rashid, Sulthan; Suriyan, Arun; Bilal Azam, Mohamed; Balasubramanian, Rajkapoor; Pakkir Maideen, Naina Mohamed; Chidambaram, Kumarappan; Amirthalingam, Palanisamy","year":2026,"journal":"Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme","doi":"10.1055/a-2787-1205","pmid":"41643685","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14726","title":"Correlation of antimicrobial peptide Human β Defensin-2 with clue cell appearance and the type of culture isolate in women with spontaneous and recurrent pregnancy losses.","authors":"Al-Khazrajy, Hind M; Al-Salihi, Siham Sh","year":2026,"journal":"Journal of immunoassay & immunochemistry, 47(1), 18-32","doi":"10.1080/15321819.2025.2549270","pmid":"40836758","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14727","title":"Identification and characterization of novel antimicrobial peptides from Camelus dromedarius: a combined bioinformatics and experimental study.","authors":"Al-Mamari, Wafa; Elhag, Yasmin; Al Bulushi, Samir; Rekha, Rokeya S; Mörman, Cecilia; Bergman, Peter; Al-Ansari, Aliya; Al-Adwani, Salma","year":2026,"journal":"Frontiers in immunology, 17, 1745714","doi":"10.3389/fimmu.2026.1745714","pmid":"41659852","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14728","title":"TRPA1 modulates urocortin 1 turnover in the centrally projecting Edinger-Westphal nucleus in a CGRP-induced migraine model.","authors":"Al-Omari, Ammar; Poszovácz, Péter; Berta, Gergely; Biró-Sütő, Tünde; Pintér, Erika; Gaszner, Balázs; Kormos, Viktória","year":2026,"journal":"Neuropharmacology, 283, 110753","doi":"10.1016/j.neuropharm.2025.110753","pmid":"41167415","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14729","title":"A Fluorescent Probe-Based Platform for Precise Pharmaceutical Analysis and Quality Assessment of Tirzepatide.","authors":"Al-Refaey, Shrouk M; El-Masry, Amal A; Hammouda, Mohammed E A; Moustafa, Mohamed A","year":2026,"journal":"Luminescence : the journal of biological and chemical luminescence, 41(2), e70442","doi":"10.1002/bio.70442","pmid":"41649304","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14730","title":"The impact of bile acid sequestrants on octreotide absorption.","authors":"Al-Tamimi, Zahraa; Feng, Mei; Elballa, Waleed; Houser, Sydney; Hageman, Michael J","year":2026,"journal":"Journal of pharmaceutical sciences, 115(2), 104153","doi":"10.1016/j.xphs.2026.104153","pmid":"41490825","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Bile acid sequestrants (BAS) reduced bile acid levels in vitro and disrupted bile acid-phospholipid mixed micelles (BAPMM), increasing the concentration of free octreotide available to cross intestinal membranes. This enhanced peptide membrane flux without compromising the enzymatic stability that micelles provide. However, the in vivo results were disappointing — oral colestipol (a BAS) did not significantly improve octreotide absorption in animals.\n\nAdditionally, cyclic E-cadherin peptide (ECP) permeation enhancers were tested but their specific in vivo results were not detailed. The study highlights that BAPMM sequestration is an important but not sole barrier to oral peptide bioavailability.","whyItMatters":"Oral delivery of peptide drugs remains one of pharmaceutical science's biggest challenges — current oral peptides have less than 1% bioavailability. This study investigated a specific mechanism (bile acid micelle trapping) that contributes to this problem and tested a potential solution. While the in vitro results were promising, the failure to improve absorption in vivo illustrates the complexity of oral peptide delivery and helps direct future research toward other barriers like enzymatic degradation and permeability.","specificNumbers":"<1% bioavailability for current oral peptides · Bile acid sequestrant tested (colestipol) · In vitro flux improved · In vivo absorption not significantly changed · BAPMM disruption confirmed","methodology":"Researchers tested the effect of bile acid sequestrants on octreotide membrane flux and enzymatic stability in vitro using models of intestinal membrane permeation. Bile acid levels and micellar structure disruption were measured. In vivo studies assessed octreotide absorption in animals after oral co-administration with the BAS colestipol. Cyclic E-cadherin peptide permeation enhancers were also evaluated.","limitations":"The in vitro improvement did not translate to in vivo bioavailability gains, suggesting the bile acid micelle barrier is only one of multiple obstacles to oral peptide absorption. Animal model results may not predict human pharmacokinetics. Specific quantitative data on in vivo absorption changes were limited in the abstract. The study focused on a single peptide (octreotide), and results may differ for other peptide drugs."},{"rthcId":"RPEP-14731","title":"Treatment outcomes and safety profile of SGLT2 inhibitors versus GLP-1 agonists in type 2 diabetes mellitus : Systematic review of real-world observational studies.","authors":"Alam, Aftab; Imran, Mohd; Ur Rehman, Zia; Sahoo, Biswa Mohan; Mahapatra, Manoj Kumar","year":2026,"journal":"Wiener medizinische Wochenschrift (1946), 176(1-2), 45-59","doi":"10.1007/s10354-025-01108-5","pmid":"40900212","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"From 22,100 research articles screened, the systematic review included observational studies comparing SGLT2 inhibitors and GLP-1 receptor agonists in real-world type 2 diabetes patients.\n\nKey pooled analysis findings:\n- Heart failure and MACE/revascularization risk ratios were slightly higher with SGLT2 inhibitors compared to GLP-1 agonists (meaning GLP-1 agonists had a slight edge for cardiovascular event reduction)\n- Renal outcome odds ratios also slightly favored GLP-1 agonists\n- However, SGLT2 inhibitors showed lower hypoglycemic events and lower all-cause mortality rates\n- SGLT2 inhibitors were more effective specifically at reducing hospitalization for heart failure\n\nThe findings suggest these drug classes have complementary strengths rather than one being universally superior.","whyItMatters":"Both SGLT2 inhibitors and GLP-1 agonists are first-line options for type 2 diabetes with cardiovascular or kidney concerns. Understanding their real-world performance differences helps clinicians choose the right drug for each patient based on their specific risk profile — heart failure risk vs. cardiovascular event risk vs. kidney disease.","specificNumbers":"","methodology":"Systematic review following PRISMA guidelines. Researchers searched EMBASE, PubMed, ClinicalTrials.gov, and Cochrane Library for studies published from January 2010 to September 2024. Only observational (real-world) studies were included; randomized controlled trials were excluded to focus on real-world clinical outcomes. Pooled analysis calculated risk ratios and odds ratios for cardiovascular, renal, hypoglycemic, and mortality outcomes.","limitations":"The review included only observational studies, which are subject to selection bias and confounding factors that randomized trials control for. The exclusion of RCTs means the findings may not establish causal relationships. Differences in study populations, drug doses, and follow-up periods across included studies could introduce heterogeneity. The review does not specify how many studies ultimately met inclusion criteria."},{"rthcId":"RPEP-14732","title":"Multi-target incretin-based therapeutics: The rise of dual and triple agonists for metabolic disorders.","authors":"Alavi, Seyed Ebrahim; Boshrouyeh, Reza; Raza, Aun; Ebrahimi Shahmabadi, Hasan","year":2026,"journal":"European journal of medicinal chemistry, 305, 118587","doi":"10.1016/j.ejmech.2026.118587","pmid":"41547240","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14733","title":"The metabolic benefits associated with semaglutide use in obese women with polycystic ovary syndrome- a retrospective study of clinical practice.","authors":"Alawami, Fatimah; Novaes, Olivia; Gibney, James; Phelan, Niamh; Behan, Lucy Ann; Owens, Lisa","year":2026,"journal":"Irish journal of medical science, 195(1), 131-136","doi":"10.1007/s11845-025-04194-x","pmid":"41283946","tags":["glp-1-receptor-agonists","metabolic-health"],"studyType":"retrospective-cohort","evidenceStrength":"moderate","keyFinding":"Across 58 obese women with PCOS treated with semaglutide in routine clinical practice, mean weight loss was 12.6 ± 9.6 kg, representing 11.4% of total body weight (p < 0.0001). Seventy-nine percent of participants lost more than 5% of their body weight — the threshold considered clinically meaningful for PCOS.\n\nMean BMI dropped from 40.7 to 36.2 kg/m² (p < 0.0001). Systolic blood pressure fell by 6.3 mmHg (p = 0.012). HbA1c decreased from 35.3 to 33 mmol/mol (p = 0.0014). Total cholesterol dropped from 4.8 to 4.45 mmol/L (p = 0.03). Among those with irregular periods, 50% reported subjective improvement, while 33% with acne and 29% with hirsutism also noted improvements.","whyItMatters":"Clinical guidelines suggest GLP-1 receptor agonists could help women with PCOS, but they've noted a lack of evidence. This study fills part of that gap with real-world data showing semaglutide delivers substantial weight loss and metabolic improvements in this specific population — well beyond the 5% weight loss threshold known to improve PCOS outcomes.","specificNumbers":"n=58; 12.6 kg mean weight loss (11.4%); BMI 40.7→36.2; SBP -6.3mmHg; HbA1c 35.3→33 mmol/mol; 79% lost >5% body weight; 50% improved menstrual cycles","methodology":"This was a retrospective review of medical records from 58 women with both PCOS and obesity who were attending reproductive endocrinology clinics and had been prescribed semaglutide for at least 6 months. The researchers collected data on weight, BMI, blood pressure, HbA1c, cholesterol, and self-reported changes in menstrual regularity, acne, and excess hair growth before and after treatment.","limitations":"This was a retrospective study with no control group, so the improvements can't be definitively attributed to semaglutide alone. Menstrual, acne, and hirsutism improvements were based on subjective patient reports rather than objective measurements. The study was conducted at a single center in Ireland. The sample size of 58 is relatively small, and there was considerable variation in individual weight loss responses (standard deviation of 9.6 kg)."},{"rthcId":"RPEP-14734","title":"Tirzepatide ameliorates type 2 diabetes-associated male reproductive dysfunction via modulation of the Nrf2/Keap1 pathway.","authors":"Albokhadaim, Ibrahim","year":2026,"journal":"Toxicology research, 15(1), tfag010","doi":"10.1093/toxres/tfag010","pmid":"41756101","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In diabetic Wistar rats treated for eight weeks, tirzepatide produced comprehensive reproductive improvements: restored testosterone and gonadotropin levels, enhanced sperm quality, reduced lipid peroxidation (oxidative fat damage), and preserved testicular architecture with increased PCNA expression (cell proliferation) and reduced caspase-3-mediated apoptosis (programmed cell death).\n\nThe protective mechanism involved activation of the Nrf2/Keap1 antioxidant pathway and normalization of steroidogenic gene expression. Crucially, a pair-fed diabetic control group demonstrated that these effects were largely independent of weight reduction — pointing to direct tissue-protective actions of tirzepatide. All reproductive outcomes were superior to those achieved with metformin.","whyItMatters":"Male infertility affects up to 50% of men with type 2 diabetes, and current diabetes treatments like metformin have limited ability to reverse reproductive damage. The finding that tirzepatide — a peptide drug already FDA-approved for diabetes and obesity — has direct reproductive protective effects independent of weight loss and blood sugar improvement opens a potential secondary benefit for millions of diabetic men struggling with fertility.","specificNumbers":"","methodology":"Sixty Wistar rats were divided into five groups: control, diabetic control, tirzepatide-treated diabetic, metformin-treated diabetic, and pair-fed diabetic control (to isolate weight-independent effects). Diabetes was induced using a high-fat diet combined with low-dose streptozotocin. Treatments were administered for eight weeks. Comprehensive assessments included metabolic parameters, reproductive hormones, sperm analysis, oxidative stress markers, testicular histology, and gene expression analysis for antioxidant (Nrf2/Keap1), steroidogenic, proliferative (PCNA), and apoptotic (caspase-3) markers.","limitations":"This is a rat study using chemically induced diabetes, which may not fully replicate human type 2 diabetes. The eight-week treatment period is relatively short. The pair-fed control design helps isolate weight-independent effects but doesn't perfectly control for all metabolic differences. Translation to human male fertility requires clinical trials — rat reproductive biology differs significantly from human. Specific tirzepatide doses used in the rat model may not correspond to clinically relevant human doses."},{"rthcId":"RPEP-14735","title":"Pancreatic β-cell turnover in health and disease.","authors":"Alcibahy, Yasmine; Darwish, Radwan; Butler, Alexandra E; Moin, Abu Saleh Md","year":2026,"journal":"Diabetes, obesity & metabolism, 28(1), 27-49","doi":"10.1111/dom.70191","pmid":"41159407","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-14736","title":"Modern Management of CKM Syndrome: Use of GLP-1 Receptor Agonists in a Multidisciplinary Setting-Expert Group Recommendations from Kuwait.","authors":"Aldahi, Waleed A; Alenezi, Abdullah; Alessa, Thamer; Alhamdan, Rashed; Al-Humood, Khaldoon A; Alqallaf, Ahmed; Alotaibi, Torki; Alrajab, Heba; Alshammari, Abdulmuhsen M; Alyousef, Anas M; Alsayed Hashem, Asrar; Rizzo, Manfredi","year":2026,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders","doi":"10.1007/s13300-025-01838-0","pmid":"41678007","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Expert consensus supports multidisciplinary CKM syndrome management with expanded GLP-1 RA access, particularly semaglutide, to address Kuwait's high burden of obesity and metabolic disease.","whyItMatters":"CKM syndrome affects millions worldwide, yet care remains fragmented across specialties. These recommendations provide a practical framework for integrated treatment in high-burden populations.","specificNumbers":"","methodology":"Expert consensus panel with literature review — Kuwaiti specialists in endocrinology, cardiology, and nephrology convened to assess barriers and define practical recommendations.","limitations":"Expert consensus rather than original research data; recommendations are specific to Kuwait's healthcare context and may not directly apply to other settings."},{"rthcId":"RPEP-14737","title":"Heterogeneity of Treatment Effects of Glucagon-Like Peptide-1 Receptor Agonists for Weight Loss in Adults: A Systematic Review and Meta-Analysis.","authors":"Alexander, G Caleb; Xiao, Xuya; Dilek, Sophie; Lewis, Sydney; Deng, Qilin; Kim, Minji; Bolanle, Dami; Saldanha, Ian J; Mehta, Hemalkumar B","year":2026,"journal":"JAMA internal medicine","doi":"10.1001/jamainternmed.2025.8222","pmid":"41770554","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 receptor agonists showed consistent weight loss efficacy across patient subgroups defined by age, sex, race/ethnicity, baseline BMI, and baseline HbA1c.","whyItMatters":"Confirming that GLP-1 RAs work consistently across diverse populations means clinicians can prescribe them confidently without worrying about reduced efficacy in certain patient groups.","specificNumbers":"","methodology":"Systematic review and meta-analysis of randomized controlled trials from MEDLINE, Embase, and Cochrane, analyzing heterogeneity of treatment effects across patient subgroups.","limitations":"Subgroup analyses from trials may have limited power to detect small differences; real-world populations may differ from clinical trial participants."},{"rthcId":"RPEP-14738","title":"Weight Changes From Glucagon-Like Peptide-1 Receptor Agonist Use and Discontinuation: A Retrospective Cohort Study.","authors":"Alexander, G Caleb; Xu, Yizhen; Xiao, Xuya; Lewis, Sydney V; Zeger, Scott; Mehta, Hemalkumar B","year":2026,"journal":"Obesity (Silver Spring, Md.), 34(2), 482-490","doi":"10.1002/oby.70076","pmid":"41271442","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Patients experienced weight regain after discontinuing GLP-1 medications, with patterns influenced by the duration of prior treatment.","whyItMatters":"Understanding weight regain patterns after stopping GLP-1 drugs is critical for setting patient expectations and planning long-term treatment strategies.","specificNumbers":"","methodology":"Retrospective cohort study using TriNetX electronic health records (2014-2023) with linear mixed effects models and propensity score adjustment.","limitations":"Retrospective design using EHR data; reasons for discontinuation unknown; BMI measurements may be irregular in real-world records."},{"rthcId":"RPEP-14739","title":"Joint TOS/OMA/OAC Expert Guidance Statement on the Pharmacological Management of United States Adults With Overweight or Obesity Using the GRADE Approach.","authors":"Alexander, Lydia; Purnell, Jonathan Q; Burridge, Karlijn; Cornier, Marc-André; Golden, Angela; Bade, Deborah; Look, Michelle; Nadglowski, Joe; Ávila-Oliver, Camila; Novillo, Francisco; Rojas-Gómez, Ana María; Hussey, Brad; Salas, Ximena Ramos","year":2026,"journal":"Obesity (Silver Spring, Md.)","doi":"10.1002/oby.70164","pmid":"41782434","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Joint expert guidance from three major U.S. obesity organizations provides updated, evidence-graded recommendations for pharmacological obesity management.","whyItMatters":"Despite effective medications being available, obesity remains undertreated due to stigma, lack of insurance coverage, and limited clinician training. Updated guidance from leading societies can help standardize care.","specificNumbers":"","methodology":"Expert guidance statement using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to systematically evaluate evidence for obesity medications.","limitations":"Guidance statement rather than systematic review; GRADE assessments depend on available trial data which may not capture long-term outcomes."},{"rthcId":"RPEP-14740","title":"The Risk of Hypothyroidism With the Use of GLP-1 Receptor Agonists in Saudi Arabia.","authors":"Alfakhri, Almaha; Almadani, Ohoud; Alroba, Raseel; Alrwisan, Adel; Alshaya, Omar; Albogami, Yasser","year":2026,"journal":"Pharmacoepidemiology and drug safety, 35(1), e70315","doi":"10.1002/pds.70315","pmid":"41490610","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 receptor agonist use was not associated with increased hypothyroidism incidence compared to DPP-4 inhibitor use in Saudi Arabian adults.","whyItMatters":"Preclinical thyroid safety signals had raised concerns about GLP-1 RAs. Real-world evidence showing no increased hypothyroidism risk helps reassure patients and clinicians.","specificNumbers":"","methodology":"Active-comparator, new-user cohort study using the Saudi Real-World Evidence Research Network (SRWEN) from 2016-2023.","limitations":"Observational design cannot prove causation; Saudi Arabian population may not be generalizable to all populations; follow-up duration may miss very late-onset effects."},{"rthcId":"RPEP-14741","title":"In vitro metabolic profiling of weight-loss-inducing amylin receptor agonists in the context of preventive doping research.","authors":"Alhalabi, Hana; Borschel, Lisa; Le Foll, Christelle; Thomas, Andreas; Bally, Lia; Thevis, Mario","year":2026,"journal":"Journal of pharmaceutical and biomedical analysis, 273, 117418","doi":"10.1016/j.jpba.2026.117418","pmid":"41702251","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In vitro metabolic profiling identified breakdown products of pramlintide, cagrilintide, and KBP-042, supporting development of anti-doping detection methods for next-generation weight loss peptides.","whyItMatters":"As weight loss peptides become more accessible, sports organizations need validated detection methods to prevent misuse in weight-sensitive athletic disciplines.","specificNumbers":"","methodology":"In vitro metabolic profiling using laboratory-based incubation systems to identify metabolites of amylin receptor agonists.","limitations":"In vitro metabolic profiling may not perfectly replicate in vivo metabolism; actual detection windows in athletes need validation through in vivo studies."},{"rthcId":"RPEP-14742","title":"Prevalence and Factors Associated with GLP-1 Receptor Agonist Use for Weight Management Among Overweight and Obese Adults in the Eastern Province of Saudi Arabia.","authors":"Alhussain, Khalid; Alshakhs, Zainab; Albaqshi, Layla; Alshaqaqiq, Fawatim; Alrabiah, Mohammed; Tripathi, Rina","year":2026,"journal":"Healthcare (Basel, Switzerland), 14(3)","doi":"10.3390/healthcare14030345","pmid":"41682196","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RA use for weight management was prevalent among overweight/obese adults in Eastern Saudi Arabia, with specific demographic and health factors predicting use.","whyItMatters":"Understanding real-world patterns of GLP-1 RA use for weight loss helps healthcare systems plan for demand, education needs, and appropriate prescribing oversight.","specificNumbers":"","methodology":"Cross-sectional survey using an online self-administered questionnaire with chi-square tests and logistic regression analysis.","limitations":"Self-reported survey data subject to recall bias; online questionnaire may not reach all demographic groups; single region limits generalizability."},{"rthcId":"RPEP-14743","title":"Rural community peer partnerships for improving methamphetamine -associated heart failure screening and engagement in cardiology care (PEER-Heart): Study protocol.","authors":"Alias-Ferri, Maria; Kersey, Cooper B; Shalen, Evan F; Cook, Ryan; Gregoire, Devin; Hoffman, Kim; Beam, Michelle; Levander, Ximena A; Pertl, Kellie; Stensby, Alexis; Gonzales, Paul; Smith, Shanna; Evernden, Tabetha; Longenecker, Chris T; Korthuis, P Todd; Chan, Brian","year":2026,"journal":"Drug and alcohol dependence reports, 18, 100411","doi":"10.1016/j.dadr.2026.100411","pmid":"41676388","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Study protocol describes a peer-led BNP screening plus telecardiology intervention designed to detect methamphetamine-associated heart failure in rural communities.","whyItMatters":"MAHF is increasingly prevalent but under-detected in rural areas. Peer-led community screening could bridge the gap between at-risk populations and specialist care.","specificNumbers":"","methodology":"Hybrid type 1 effectiveness-implementation trial protocol with peer-assisted point-of-care BNP screening and telecardiology follow-up.","limitations":"Study protocol only — no efficacy or feasibility results yet; rural Oregon context may not generalize to all settings."},{"rthcId":"RPEP-14744","title":"GLP-1 receptor agonists and next-generation metabolic hormone therapies in chronic kidney disease.","authors":"Alicic, Radica Z; Neumiller, Joshua J; Tuttle, Katherine R","year":2026,"journal":"Nature reviews. Nephrology","doi":"10.1038/s41581-025-01036-y","pmid":"41507425","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RAs and emerging metabolic hormone therapies show significant potential for slowing CKD progression, particularly within the CKM syndrome framework.","whyItMatters":"CKD affects hundreds of millions worldwide and is closely linked to diabetes and obesity. Repurposing metabolic therapies for kidney protection could transform CKD management.","specificNumbers":"","methodology":"Narrative review synthesizing clinical trial data, mechanistic studies, and guideline recommendations for incretin-based CKD therapies.","limitations":"Narrative review — selective in literature coverage; dedicated CKD outcome trials for newer agents are still ongoing."},{"rthcId":"RPEP-14745","title":"Impact of Semaglutide on fat mass, lean mass and muscle function in patients with obesity: The SEMALEAN study.","authors":"Alissou, Mathieu; Demangeat, Thomas; Folope, Vanessa; Van Elslande, Hélène; Lelandais, Hélène; Blanchemaison, Julia; Cailleaux, Pierre-Emmanuel; Guney, Suzan; Aupetit, Alexandra; Aubourg, Agnès; Rapp, Clément; Petit, André; Godin, Morgane; Vignal, Luc; Grigioni, Sébastien; Déchelotte, Pierre; Colange, Guillaume; Coëffier, Moïse; Achamrah, Najate","year":2026,"journal":"Diabetes, obesity & metabolism, 28(1), 112-121","doi":"10.1111/dom.70141","pmid":"41068996","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide 2.4mg produced significant weight and fat loss but also reduced lean body mass, while handgrip strength was generally preserved through 12 months.","whyItMatters":"The lean mass loss debate is one of the biggest concerns with GLP-1 medications. This study provides objective DXA-measured data showing the actual body composition changes during semaglutide treatment.","specificNumbers":"","methodology":"Prospective observational study with 115 patients; body composition measured by DXA, muscle function by handgrip strength, and resting energy expenditure tracked at baseline, 7 months, and 12 months.","limitations":"No control group; prospective but observational design; handgrip strength is a limited measure of overall muscle function."},{"rthcId":"RPEP-14746","title":"GLP-1 receptor agonists in kidney transplant recipients with type 2 diabetes mellitus: a systematic review and meta-analysis on mortality and major adverse kidney events.","authors":"Aliyeva, Turkan; Natche, Julia; Jiakponna, Enyinnaya Calistus; Ahmad, Feras; Eze, Belinda; Nawaz, Usama Hassan; El-Amri, Imane; Shrestha, Sheelu","year":2026,"journal":"Journal of diabetes and metabolic disorders, 25(1), 29","doi":"10.1007/s40200-025-01801-7","pmid":"41522206","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Limited retrospective evidence suggests GLP-1 RAs may be safe regarding mortality, MACE, and MAKE in kidney transplant recipients with type 2 diabetes.","whyItMatters":"Kidney transplant patients with diabetes need effective glucose and weight management but face unique risks. Establishing GLP-1 RA safety in this population could expand treatment options.","specificNumbers":"","methodology":"Systematic review and meta-analysis of retrospective cohort studies examining GLP-1 RA outcomes in adult kidney transplant recipients.","limitations":"Based entirely on retrospective cohort data — no RCTs available; small pooled sample sizes limit statistical power; transplant-specific confounders difficult to control."},{"rthcId":"RPEP-14747","title":"Design and Efficacy of an Ultrashort Antimicrobial Peptide-levofloxacin Conjugate Against Resistant Bacteria: A Novel Approach to Combat Antimicrobial Resistance.","authors":"Almaaytah, Ammar; Rashdan, Aseel; Mhaidat, Nizar; Sabi, Salsabeel H","year":2026,"journal":"Current pharmaceutical biotechnology","doi":"10.2174/0113892010392077251119101656","pmid":"41588908","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"UP5-C-Levo demonstrated enhanced antimicrobial activity against resistant bacteria compared to its individual components, with improved safety.","whyItMatters":"Antimicrobial resistance is a global health crisis. Peptide-antibiotic conjugates represent a novel approach to overcoming resistance while addressing the toxicity limitations of standalone antimicrobial peptides.","specificNumbers":"","methodology":"Chemical synthesis of peptide-antibiotic conjugate followed by in vitro antimicrobial activity testing against multidrug-resistant bacterial strains and cytotoxicity assessment.","limitations":"In vitro study only — no in vivo animal model data yet; stability and pharmacokinetics in biological systems untested."},{"rthcId":"RPEP-14748","title":"Nutritional status with tirzepatide in obesity: A post hoc analysis of the SURMOUNT-1-4 randomized clinical trials.","authors":"Almandoz, Jaime P; Pickett-Blakely, Octavia; Tewksbury, Colleen; Stefanski, Adam; Gonsahn-Bollie, Sylvia; Dimitriadis, Georgios K; Murro, Ada Leticia; Cao, Dachuang; Meng, Qier; Neff, Lisa M","year":2026,"journal":"Obesity pillars, 17, 100248","doi":"10.1016/j.obpill.2026.100248","pmid":"41640675","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tirzepatide treatment across the SURMOUNT-1-4 trials was not associated with worsening nutritional status despite appetite and dietary intake reduction.","whyItMatters":"A major concern with potent appetite suppressants is that patients may not get adequate nutrition. This data is reassuring for the millions using or considering tirzepatide.","specificNumbers":"","methodology":"Post hoc descriptive analysis of nutritional data from four randomized, placebo-controlled, phase 3 trials (SURMOUNT-1 through SURMOUNT-4).","limitations":"Post hoc analysis — not designed primarily to assess nutritional outcomes; descriptive statistics limit causal conclusions; trial populations may not represent all real-world users."},{"rthcId":"RPEP-14749","title":"Peptide-assisted direct detection of HPV nucleic acids from liquid-based cytology samples without extraction.","authors":"Almas, Sadia; Karki, Salima; Carpenter, Rob E; Tamrakar, Vaibhav K; Sharma, Aditya; Suri, Kamalpreet; Sharma, Rahul","year":2026,"journal":"Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology, 182, 105901","doi":"10.1016/j.jcv.2025.105901","pmid":"41330276","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"MDP-1 peptide enables direct detection of HPV nucleic acids from liquid cytology samples without requiring nucleic acid extraction.","whyItMatters":"Eliminating the DNA extraction step could dramatically reduce the cost and complexity of HPV screening, making it accessible in low-resource settings where cervical cancer burden is highest.","specificNumbers":"","methodology":"Rational peptide design targeting HPV capsid proteins, validated using PCR-based detection on PreservCyt liquid-based cytology samples.","limitations":"Early-stage proof-of-concept; clinical validation across diverse HPV types and sample conditions needed; regulatory pathway for diagnostic use not yet addressed."},{"rthcId":"RPEP-14750","title":"The role of GIP in carbohydrate metabolism: Implications in the development of therapies for T2DM, a narrative review.","authors":"Almorza-Gomar, David; Díaz-Gómez, Alfredo; Visiedo, Francisco; García-Ortiz, José-Carlos; Camacho-Ramírez, Alonso; Ribelles-García, Antonio; Prada-Oliveira, José-Arturo; Pérez-Arana, Gonzalo-Martín","year":2026,"journal":"Histology and histopathology, 41(3), 371-381","doi":"10.14670/HH-18-967","pmid":"40755350","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GIP is emerging as a critical therapeutic target alongside GLP-1, with dual agonists showing enhanced efficacy for type 2 diabetes management.","whyItMatters":"Understanding GIP's contribution to glucose regulation explains why dual agonists like tirzepatide appear more effective than GLP-1 alone, opening new avenues for diabetes treatment.","specificNumbers":"","methodology":"Narrative review of GIP biology, its role in carbohydrate metabolism, and implications for T2DM drug development.","limitations":"Narrative review — selective literature coverage; GIP's complex biology (including potential detrimental effects) not fully resolved."},{"rthcId":"RPEP-14751","title":"Glucagon-Like Peptide-1 Receptor Agonists as Adjunctive Therapy for Hidradenitis Suppurativa in Patients With Overweight/Obesity: A Narrative Review of Efficacy, Safety, and Quality-of-Life Outcomes.","authors":"Almukhadeb, Eman; Nagshabandi, Khalid Nabil; Alshehri, Naif; Alosaimi, Khalid; Almusa, Hala Abdullah; Almudimeegh, Almuntsrbellah","year":2026,"journal":"International journal of dermatology","doi":"10.1111/ijd.70346","pmid":"41729201","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Emerging evidence suggests GLP-1 RAs may improve HS outcomes in obese patients through combined weight reduction and anti-inflammatory mechanisms.","whyItMatters":"HS is debilitating and obesity worsens it significantly. If GLP-1 RAs can address both obesity and HS simultaneously, this could improve quality of life for a poorly served patient population.","specificNumbers":"","methodology":"Narrative review synthesizing available human evidence on incretin-based therapies for hidradenitis suppurativa.","limitations":"Narrative review based on limited human evidence; no large RCTs of GLP-1 RAs specifically for HS outcomes."},{"rthcId":"RPEP-14752","title":"The lack of efficacy of tirzepatide in mitigating cisplatin-induced neurotoxicity and cognitive impairment in rats.","authors":"Almutairi, Hanan Mubarak; Alhowail, Ahmad Hamad","year":2026,"journal":"Frontiers in toxicology, 8, 1752511","doi":"10.3389/ftox.2026.1752511","pmid":"41625437","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tirzepatide did not protect against cisplatin-induced neurotoxicity or cognitive impairment in female rats.","whyItMatters":"The negative result is important — it tempers enthusiasm for repurposing GLP-1/GIP agonists as neuroprotective agents in the chemotherapy setting.","specificNumbers":"","methodology":"Preclinical animal study with 40 female Wistar rats in four groups (control, cisplatin, tirzepatide, cisplatin + tirzepatide) assessing neurotoxicity endpoints.","limitations":"Animal model — rat neurotoxicity may not perfectly mirror human chemobrain; single dose/duration tested; only female rats used."},{"rthcId":"RPEP-14753","title":"Dual-Channel Fluorescence Assays with Supramolecular Host-Dye Reporter Pairs for Membrane Activity Mapping of Peptides.","authors":"Alnajjar, Mohammad A; Schöpper, Sandra N; Pramod, Malavika; Reingolz, Thomas; Müller, Lina; Neumann, Justin; Nilam, Mohamed; Nau, Werner M; Hennig, Andreas","year":2026,"journal":"Angewandte Chemie (International ed. in English), 65(5), e17709","doi":"10.1002/anie.202517709","pmid":"41388792","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A dual-channel fluorescence assay can distinguish between cell-penetrating and pore-forming peptide mechanisms by mapping different patterns of membrane permeabilization.","whyItMatters":"Understanding whether a peptide penetrates or damages membranes is critical for developing peptide-based drugs and antibiotics with the right activity profile.","specificNumbers":"","methodology":"Development of a fluorescence-based dual-channel assay using carboxyfluorescein efflux combined with a supramolecular host-dye reporter system on liposomal membranes.","limitations":"In vitro liposomal model — may not capture the complexity of real cell membranes; limited peptide panel tested."},{"rthcId":"RPEP-14754","title":"Efficacy and safety of orforglipron, an oral small-molecule GLP-1 receptor agonist, on cardiometabolic outcomes: a meta-analysis and systematic review.","authors":"Alper, Adir; Peleg, Gal; Fagin, Adina; Shah, Priyansh; Chowdhury, Ishmum; Gonzales, Antony; Faillace, Robert","year":2026,"journal":"Cardiovascular diabetology. Endocrinology reports, 12(1), 9","doi":"10.1186/s40842-025-00270-4","pmid":"41715239","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Orforglipron demonstrated significant improvements in weight, HbA1c, blood pressure, and lipid parameters across pooled phase 2 and 3 trial data.","whyItMatters":"Many patients avoid GLP-1 medications due to injection hesitancy. An effective once-daily oral pill could dramatically expand access to these cardiometabolic benefits.","specificNumbers":"","methodology":"PRISMA-compliant systematic review and meta-analysis of placebo-controlled phase 2 and phase 3 RCTs (PROSPERO registered).","limitations":"Phase 2/3 trial data — long-term cardiovascular outcome data not yet available; meta-analysis limited by number of completed trials."},{"rthcId":"RPEP-14755","title":"Comparative Effectiveness of Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors Versus Glucagon-Like Peptide-1 (GLP-1) Agonists on Cardiovascular and Renal Outcomes in Type 2 Diabetes: A Systematic Review and Network Meta-Analysis.","authors":"Alqurain, Aymen A; Salem, Manal; Algarzai, Bashayer A; Eljadi, Eman M; Elsayed, Hazem S; Almuhanna, Ahmed; Albuhayji, Deema S; Salami, Mohammad; Alzahrani, Joud; Alsayyali, Juri; Alqarni, Abdulrahman; Alqahtani, Nessreen; Alotaibi, Fay T; Alyami, Gharam G","year":2026,"journal":"Cureus, 18(1), e100927","doi":"10.7759/cureus.100927","pmid":"41523725","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Both SGLT2 inhibitors and GLP-1 RAs significantly reduce cardiovascular and renal events in type 2 diabetes, with potential differential benefits for specific outcomes.","whyItMatters":"Clinicians need guidance on choosing between SGLT2 inhibitors and GLP-1 RAs (or using both) for patients with type 2 diabetes at cardiovascular/renal risk.","specificNumbers":"","methodology":"Systematic review and network meta-analysis of large-scale placebo-controlled cardiovascular outcome trials using frequentist methods.","limitations":"Network meta-analysis relies on indirect comparisons — inherently less reliable than direct head-to-head trials; heterogeneity across trials may affect results."},{"rthcId":"RPEP-14756","title":"Pancreatic Mucinous Cystic Neoplasms Following GLP-1 Receptor Agonists Use: A Report of Two Cases with Literature Review.","authors":"Alsaleh, Nourah Mohammed; Abo Alshamat, Renad; Almrzouqi, Wejdan; Alhebshi, Mohammed; Aljuhani, Turky; Almahdi, Rahf; Almaghrabi, Majed; Rammal, Almotasembillah; Ageel, Amro; Alzahrani, Mohammed Ahmad","year":2026,"journal":"Journal of gastrointestinal cancer, 57(1), 28","doi":"10.1007/s12029-025-01377-8","pmid":"41609941","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Two patients without typical risk factors developed pancreatic mucinous cystic neoplasms following GLP-1 RA use, suggesting a possible association requiring further investigation.","whyItMatters":"While pancreatic safety has been a recurring concern with GLP-1 RAs, associations with cystic neoplasms (as opposed to pancreatitis) have rarely been reported and warrant monitoring.","specificNumbers":"","methodology":"Case report of two patients — descriptive clinical observation with literature review.","limitations":"Case report — cannot establish causation; two cases is insufficient to determine true risk; temporal association does not prove causal relationship."},{"rthcId":"RPEP-14757","title":"A Bibliometric Analysis Review of the Top 50 Most Cited Articles on Incretin-Based Therapy for Weight Reduction and Diabetes Management.","authors":"Alsaygh, Ehab F; Aljarboa, Abdullah M; Alhazmi, Adel A; Alhazmi, Abdullah S; Alraddadi, Osamah A; Althagafi, Aseel A; Alhojele, Mohmmed F","year":2026,"journal":"Cureus, 18(1), e102500","doi":"10.7759/cureus.102500","pmid":"41769631","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The most influential incretin therapy publications cluster around GLP-1 RA efficacy, cardiovascular outcomes, and weight management — reflecting the field's rapid clinical expansion.","whyItMatters":"Mapping the most influential research helps new researchers identify foundational studies and understand where the field is moving.","specificNumbers":"","methodology":"Bibliometric analysis of the 50 most-cited articles from the Web of Science database, with citation pattern and trend analysis.","limitations":"Bibliometric analysis captures citation impact, not clinical importance; older articles have citation advantage; database limited to Web of Science."},{"rthcId":"RPEP-14758","title":"Deep Venous Thrombosis Within Two Weeks of Initiating Oral Semaglutide (Rybelsus): A Case Report.","authors":"Alsermani, Maamoun; Ali Alkahmous, Baraa; Alhutayrashi, Arwa A; Alshalhoob, Fai S; Abulrahman Almosaiteer, Sarah; Aljubayri, Eman; Saleh Alwabel, Assia; Sermani, Anas","year":2026,"journal":"Cureus, 18(1), e100836","doi":"10.7759/cureus.100836","pmid":"41646548","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A 16-year-old developed acute DVT within 14 days of starting oral semaglutide 7mg, suggesting a possible temporal association with GLP-1 RA initiation.","whyItMatters":"GLP-1 RAs are increasingly prescribed off-label to younger patients for weight management. Any potential thromboembolic signal in this population warrants attention.","specificNumbers":"","methodology":"Case report — single patient clinical observation.","limitations":"Single case report — cannot establish causation; patient had pre-existing risk factors (overweight, sedentary); temporal coincidence possible."},{"rthcId":"RPEP-14759","title":"Developing a Comprehensive Approach for Managing Cardiorenal Metabolic Diseases (CRMD) in Saudi Arabia: Thinking beyond Single Disease-Literature Review and Multidisciplinary Consensus Report.","authors":"Alshaikh, Abdulrahman; Alshehri, Ali; Alzubaidi, Lamya; Elbadawi, Hussein; Alsaeed, Abdulghani; Almehthel, Mohammed; Aldahash, Raed; Alsabaan, Fahad; Alotaibi, Metib; Alghamdi, Khalid; Alamri, Hussein; Bakhsh, Abdulmohsen; Evans, Marc; Issak, Emad R; Alsifri, Saud","year":2026,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 17(2), 165-183","doi":"10.1007/s13300-025-01826-4","pmid":"41317223","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Saudi consensus panel recommends integrated CRMD management with semaglutide as a cornerstone therapy, citing robust evidence across glycemic, weight, cardiovascular, renal, and hepatic outcomes.","whyItMatters":"Saudi Arabia faces high metabolic disease prevalence. Integrated management frameworks with proven therapies like semaglutide could significantly reduce disease burden.","specificNumbers":"","methodology":"Literature review and multidisciplinary expert consensus from Saudi endocrinologists, cardiologists, nephrologists, and hepatologists.","limitations":"Consensus report — reflects expert opinion rather than new data; Saudi-specific context may limit broader applicability."},{"rthcId":"RPEP-14760","title":"Clinical and metabolic profile of adults with obesity attending lifestyle medicine clinics.","authors":"AlTaib, Hanan N; AlAqeel, Reem; Arafat, Amr A; Kunnathodi, Faisal; AlShaikh, Abdulmajeed; AlOtaibi, Haifa F","year":2026,"journal":"PloS one, 21(2), e0342153","doi":"10.1371/journal.pone.0342153","pmid":"41628129","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Liraglutide combined with lifestyle modification was more effective than lifestyle modification alone for weight loss in Saudi adults with obesity and comorbidities.","whyItMatters":"Real-world evidence from structured obesity care programs in non-Western settings is limited. This study demonstrates GLP-1 RA effectiveness in Saudi primary care.","specificNumbers":"","methodology":"Retrospective cohort study at a primary care center in Prince Sultan Military Medical City, Riyadh (2023-2024); adults with BMI 30-40 and ≥1 obesity-related comorbidity.","limitations":"Retrospective design; single center at a military medical facility; selection bias possible between treatment groups."},{"rthcId":"RPEP-14761","title":"Clinical Presentation of a Child With a Novel ALMS1 Variant Associated With Alström Syndrome and Favorable Response to GLP-1 Receptor Agonist Therapy.","authors":"Alvarez, Griselda; Huang, Alden; Grody, Wayne W; Yazdani, Shahram","year":2026,"journal":"American journal of medical genetics. Part A","doi":"10.1002/ajmga.70055","pmid":"41549937","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A child with a novel ALMS1 nonsense variant and Alström syndrome showed favorable metabolic response to GLP-1 RA therapy.","whyItMatters":"Rare genetic obesity syndromes have few treatment options. Demonstrating GLP-1 RA efficacy in Alström syndrome could expand therapeutic options for these underserved patients.","specificNumbers":"","methodology":"Case report with genetic analysis identifying a novel homozygous ALMS1 variant (c.4740C>G, p.Tyr1580Ter) in exon 8.","limitations":"Single case report — response in one patient cannot predict efficacy across all Alström syndrome patients; long-term outcomes unknown."},{"rthcId":"RPEP-14762","title":"NetMHCIIphosPan: a machine learning tool for predicting HLA class II antigen presentation of phosphorylated peptides.","authors":"Alvarez, Heli M Garcia; Kaabinejadian, Saghar; Yari, Hooman; Shepherd, Chloe M; Hildebrand, William H; Sette, Alessandro; Peters, Bjoern; Parker, Robert; Ternette, Nicola; Nielsen, Morten","year":2026,"journal":"bioRxiv : the preprint server for biology","doi":"10.64898/2026.01.05.697746","pmid":"41542563","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"NetMHCIIphosPan achieves superior prediction of HLA class II presentation of phosphorylated peptides compared to existing methods.","whyItMatters":"Predicting which modified peptides are presented to the immune system is crucial for designing vaccines, immunotherapies, and understanding autoimmune responses.","specificNumbers":"","methodology":"Machine learning model trained on reanalyzed mass spectrometry immunopeptidomics datasets with refined peptide identification workflow.","limitations":"Preprint (bioRxiv) — not yet peer-reviewed; prediction accuracy depends on training data quality and HLA coverage."},{"rthcId":"RPEP-14763","title":"The Intersection of Heart Failure and Chronic Kidney Disease: Challenges in Co-management.","authors":"Alvi, Amaan; Singamala, Hithyshi; Gadde, Sai Surya Vamsi; Javvaji, Chaitanya Kumar","year":2026,"journal":"Cureus, 18(1), e100993","doi":"10.7759/cureus.100993","pmid":"41658812","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Systematic exclusion of CKD patients from heart failure trials creates major evidence gaps for co-management of these frequently coexisting conditions.","whyItMatters":"Millions of patients have both heart failure and CKD, yet clinicians must make treatment decisions with limited evidence specifically tested in this combined population.","specificNumbers":"","methodology":"Narrative review of pathophysiology, clinical trial evidence, and management challenges for coexisting heart failure and CKD.","limitations":"Narrative review — selective literature coverage; does not generate new evidence to fill the identified gaps."},{"rthcId":"RPEP-14764","title":"Potential Molecular Targets of the Broad-Range Antimicrobial Peptide Tyrothricin in the Apicomplexan Parasite Toxoplasma gondii.","authors":"Amdouni, Yosra; Boubaker, Ghalia; Müller, Joachim; Sousa, Maria Cristina Ferreira de; Hänggeli, Kai Pascal Alexander; Uldry, Anne-Christine; Braga-Lagache, Sophie; Heller, Manfred; Hemphill, Andrew","year":2026,"journal":"Biomedicines, 14(1)","doi":"10.3390/biomedicines14010172","pmid":"41595705","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tyrothricin inhibited T. gondii tachyzoite proliferation in vitro, with proteomics identifying potential molecular targets in the parasite.","whyItMatters":"Toxoplasmosis treatment options are limited and often toxic. Antimicrobial peptides could offer new therapeutic approaches for this common parasitic infection.","specificNumbers":"","methodology":"In vitro study combining proliferation inhibition assays, electron microscopy, host cell and embryo toxicity testing, and differential affinity chromatography with mass spectrometry.","limitations":"In vitro study only — no in vivo animal infection model; tyrothricin is typically used topically, and systemic use may face toxicity challenges."},{"rthcId":"RPEP-14765","title":"Gut microbes modulate Helicoverpa armigera immunity and affect its susceptibility to microbial pathogens.","authors":"Amiri Domari, Motahareh; Khani, Abbas; Sahebzadeh, Najmeh; Najimi, Mohsen; Mehrabadi, Mohammad","year":2026,"journal":"Journal of invertebrate pathology, 216, 108553","doi":"10.1016/j.jip.2026.108553","pmid":"41605325","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Gut microbiome removal altered antimicrobial peptide expression and pathogen susceptibility in H. armigera larvae.","whyItMatters":"Understanding how pest insect gut microbiomes influence immunity could improve biological pest control strategies by identifying ways to make pests more vulnerable to biocontrol agents.","specificNumbers":"","methodology":"Antibiotic-mediated gut microbiome depletion followed by immune gene expression analysis and pathogen susceptibility testing in caterpillar larvae.","limitations":"Laboratory study — field conditions with complex microbiome dynamics may differ; antibiotic treatment may have off-target effects beyond microbiome depletion."},{"rthcId":"RPEP-14766","title":"Association of glucagon-like peptide-1 receptor agonist use with anxiety disorders, depression, self-harm, and suicidality: a large cohort study.","authors":"Anagnostakis, Filippos; Kokkorakis, Michail; Anastasiou, Georgia; Nagarajan, Shrihari; Mantzoros, Christos S","year":2026,"journal":"Diabetes research and clinical practice, 233, 113104","doi":"10.1016/j.diabres.2026.113104","pmid":"41592697","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RA use was associated with lower incidence of anxiety, depression, self-harm, and suicidality compared to DPP-4i, sulfonylureas, and SGLT2i in propensity-matched cohorts.","whyItMatters":"With millions taking GLP-1 RAs, understanding their mental health effects is critical — this study suggests potential psychiatric benefits rather than harm.","specificNumbers":"","methodology":"Large propensity score-matched cohort study using TriNetX electronic health records (2013-2019); three active comparator cohorts.","limitations":"Observational design cannot prove causation; EHR data may miss mental health events not coded in records; healthy user bias possible."},{"rthcId":"RPEP-14767","title":"Comparative effectiveness of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists for incident dementia: A retrospective multicohort study.","authors":"Anagnostakis, Filippos; Kokkorakis, Michail; Nagarajan, Shrihari; Anastasiou, Georgia; Mantzoros, Christos S","year":2026,"journal":"Diabetes, obesity & metabolism, 28(2), 1443-1452","doi":"10.1111/dom.70336","pmid":"41309383","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 receptor agonists and SGLT2 inhibitors showed equivalent dementia risk (HR 1.01, 95% CI 0.90–1.13) in propensity-matched diabetic adults.","whyItMatters":"As both drug classes gain wider use, this study reassures patients and clinicians that choosing between GLP-1 RAs and SGLT2 inhibitors need not be driven by dementia concerns—neither appears riskier for cognitive decline.","specificNumbers":"","methodology":"Retrospective cohort study using TriNetX electronic health records (2013–2019) with 1:1 propensity score matching and Cox proportional hazards models.","limitations":"Retrospective design limits causal inference. The study could not account for duration or dosing of therapy, and newer agents like tirzepatide were not assessed."},{"rthcId":"RPEP-14768","title":"Light-aversion and cephalic allodynia in an intravenous CGRP model of migraine-like behaviour in male and female rats.","authors":"Andersen, Veronika K; Hansen, Bjarke S; Fungbrant, Emelie; Hestehave, Sara; Haanes, Kristian A; Nordahl, Karin M L","year":2026,"journal":"The journal of headache and pain, 27(1), 45","doi":"10.1186/s10194-026-02278-2","pmid":"41572144","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Intravenous CGRP induced light-aversion and cephalic allodynia in male and female rats, providing a translational model for migraine photophobia.","whyItMatters":"Better animal models for migraine photophobia are needed to develop and test new treatments. This IV model is more clinically relevant than intracranial injection approaches.","specificNumbers":"","methodology":"Preclinical study using IV CGRP injection in male and female rats with behavioral assessment of light-aversion and facial sensitivity at controlled light intensities.","limitations":"Animal model — rat behavior may not perfectly mirror human migraine photophobia; IV CGRP pharmacokinetics differ between species."},{"rthcId":"RPEP-14769","title":"Use of SGLT2 inhibitors and GLP-1 receptor agonists in patients with ischaemic heart disease and type 2 diabetes in Swedish primary care: a cross-sectional analysis of regional primary care registry data (QregPV).","authors":"Andersson, Tobias; Bager, Johan-Emil; Hellgren, Margareta; Åberg, Maria; Mourtzinis, Georgios","year":2026,"journal":"BMJ open, 16(2), e110395","doi":"10.1136/bmjopen-2025-110395","pmid":"41628920","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"SGLT2i and GLP-1 RA prescribing rates are substantially below guideline recommendations in Swedish primary care patients with IHD and T2D.","whyItMatters":"Even in a well-organized healthcare system like Sweden's, guideline-recommended therapies are underused, highlighting a global implementation gap.","specificNumbers":"","methodology":"Cross-sectional analysis of QregPV regional primary care quality registry data (September 2023); 209 healthcare centers; 14,414 patients.","limitations":"Cross-sectional design captures a single time point; registry data may not capture all contraindications or clinical rationale for non-prescribing."},{"rthcId":"RPEP-14770","title":"Unexpected Residual Gastric Contents in a Patient After Holding Semaglutide After Standard Fasting Guidelines: A Case Report.","authors":"Ando, Kazuo; Takenoshita, Moe; Wei, Mike Tzuhen","year":2026,"journal":"A&A practice, 20(2), e02161","doi":"10.1213/XAA.0000000000002161","pmid":"41705849","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Standard fasting guidelines plus withholding one semaglutide dose may not reliably ensure gastric emptying before endoscopy, with effects varying even in the same patient.","whyItMatters":"Millions of GLP-1 RA users will need sedated procedures. Inconsistent gastric emptying poses aspiration risk and creates anesthesia management challenges.","specificNumbers":"","methodology":"Case report comparing two endoscopy experiences in the same patient on semaglutide with identical preparation protocols.","limitations":"Single case with inconsistent findings — the variable outcome makes it harder to draw conclusions than a consistent finding would."},{"rthcId":"RPEP-14771","title":"A real-world study of tirzepatide for weight loss in adults without diabetes mellitus.","authors":"Angelopoulos, Nikolaos; Androulakis, Ioannis; Rizoulis, Andreas; Boniakos, Anastasios; Fousteris, Evangelos; Mentzelopoulou, Voula; Petkova, Valentina; Paparodis, Rodis; Zianni, Dimitra; Florakis, Dimos; Korakovouni, Areti; Mouslech, Zadalla; Livadas, Sarantis; Tzoulis, Ploutarchos","year":2026,"journal":"International journal of obesity (2005), 50(3), 684-688","doi":"10.1038/s41366-025-01986-0","pmid":"41354867","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Low-dose tirzepatide (2.5-5mg) produced significant weight loss and metabolic improvements in 12 weeks in adults with obesity without diabetes.","whyItMatters":"Real-world evidence at lower doses and shorter durations helps set realistic expectations for patients starting tirzepatide and supports cost-effective prescribing.","specificNumbers":"","methodology":"Prospective multicenter observational study; 115 adults with obesity without diabetes; tirzepatide 2.5mg (4 weeks) then 5mg (8 weeks); anthropometric and biochemical assessments.","limitations":"No control group; observational design; 12 weeks is short for assessing sustainable weight loss; small sample."},{"rthcId":"RPEP-14772","title":"Effects of combined intraduodenal administration of lauric acid and L-tryptophan on postprandial plasma glucose, glucoregulatory hormones and gastric emptying in type 2 diabetes: a double-blind, randomised, crossover study.","authors":"Anjom-Shoae, Javad; Fitzgerald, Penelope C E; Rose, Braden D; Bitarafan, Vida; Rehfeld, Jens F; Horowitz, Michael; Feinle-Bisset, Christine","year":2026,"journal":"Diabetologia, 69(4), 900-910","doi":"10.1007/s00125-025-06630-0","pmid":"41419616","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Combined intraduodenal lauric acid and L-tryptophan synergistically stimulated GLP-1/CCK release and reduced postprandial glucose in type 2 diabetes.","whyItMatters":"This synergistic nutrient approach could inspire non-pharmacological or food-based strategies for blood sugar management using the gut's own hormone release system.","specificNumbers":"","methodology":"Randomized, double-blind, crossover study with intraduodenal nutrient infusion in type 2 diabetes patients.","limitations":"Intraduodenal delivery is not practical for routine use; unclear if oral delivery of these nutrients achieves similar effects; small crossover study."},{"rthcId":"RPEP-14773","title":"Strategies to improve intracellular delivery of arginine-rich cell-penetrating peptides.","authors":"Anjous, Rachel; Kavyashree, P; Saha, Abhishek","year":2026,"journal":"Journal of materials chemistry. B","doi":"10.1039/d5tb02935j","pmid":"41773590","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Multiple strategies — structural modifications, conjugation, and formulation approaches — can significantly enhance arginine-rich CPP intracellular delivery efficiency.","whyItMatters":"Efficient intracellular drug delivery is one of the biggest challenges in medicine. Improving CPP technology could enable treatments for previously undruggable targets.","specificNumbers":"","methodology":"Literature review of strategies to improve arginine-rich cell-penetrating peptide delivery performance.","limitations":"Review article — synthesizes existing research without generating new data; clinical translation of CPP strategies remains challenging."},{"rthcId":"RPEP-14774","title":"Cathelicidin LL-37-Induced Transcriptome of Human Keratinocyte Identifies Chemokine CXCL10 Link to T-Cell-Mediated Rosacea Pathogenesis through Jak1/STAT1 Pathway.","authors":"Ansari, Abdul W; Habib, Tanwir; Ahmad, Fareed; Raheed, Thesni; Elizabeth, Cynthia S; Al-Harami, Sara; Jochebeth, Anh; Steinhoff, Martin","year":2026,"journal":"The Journal of investigative dermatology, 146(3), 711-721.e6","doi":"10.1016/j.jid.2025.08.003","pmid":"40835085","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"LL-37 drives rosacea pathogenesis by activating Jak1/STAT1 signaling in keratinocytes, inducing CXCL10-mediated T-cell recruitment to the skin.","whyItMatters":"Identifying the specific signaling pathway from LL-37 to T-cell recruitment opens targeted therapeutic opportunities for rosacea, including Jak inhibitors.","specificNumbers":"","methodology":"Transcriptome profiling of LL-37-treated normal human keratinocytes, followed by pathway analysis identifying Jak1/STAT1 and CXCL10 as key mediators.","limitations":"In vitro keratinocyte model — may not capture the full complexity of rosacea pathogenesis in intact skin with multiple cell types."},{"rthcId":"RPEP-14775","title":"Modulating CGRP Signaling: A Promising Therapeutic Avenue for Attenuating Cardiac Dysfunction in Heart Failure.","authors":"Ansari, Shazia; Aran, Khadga Raj","year":2026,"journal":"Cardiovascular drugs and therapy","doi":"10.1007/s10557-025-07830-x","pmid":"41546811","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CGRP offers multiple cardioprotective mechanisms — vasodilation, anti-inflammation, anti-fibrosis, and neurohormonal counterregulation — that may be therapeutically exploitable in heart failure.","whyItMatters":"Current heart failure treatments have limitations. CGRP-based therapies could provide a novel approach addressing multiple pathological mechanisms simultaneously.","specificNumbers":"","methodology":"Narrative review of CGRP biology and its role in cardiovascular homeostasis and heart failure pathophysiology.","limitations":"Narrative review — mostly based on preclinical evidence; clinical translation of CGRP modulation for heart failure is still theoretical."},{"rthcId":"RPEP-14776","title":"Antimicrobial peptides at (lipid) interfaces: Insights from monolayer models.","authors":"Antelo-Riveiro, Paula; Garcia-Fandino, Rebeca; Piñeiro, Ángel","year":2026,"journal":"Advances in colloid and interface science, 350, 103775","doi":"10.1016/j.cis.2025.103775","pmid":"41506087","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Lipid monolayer models reveal that AMP selectivity is driven by specific lipid signatures that differentiate bacterial, cancerous, and senescent cell membranes from healthy cells.","whyItMatters":"Understanding how AMPs distinguish between harmful and healthy cells is essential for designing peptide therapies that kill pathogens or cancer cells without damaging normal tissue.","specificNumbers":"","methodology":"Critical review of lipid monolayer biophysical studies examining antimicrobial peptide-membrane interactions and selectivity mechanisms.","limitations":"Monolayer models are reductionist — they mimic only the outer leaflet and lack the complexity of real bilayer membranes with proteins and carbohydrates."},{"rthcId":"RPEP-14777","title":"Evolving trends of antidiabetic agents stratified by age, kidney function and body mass index: Insights from a nationwide claims database.","authors":"Aoyama, Kazuki; Okada, Akira; Kaneko, Hidehiro; Azegami, Tatsuhiko; Suzuki, Yuta; Meguro, Shu; Fujiu, Katsuhito; Takeda, Norifumi; Morita, Hiroyuki; Node, Koichi; Yamauchi, Toshimasa; Nangaku, Masaomi; Takeda, Norihiko; Yasunaga, Hideo; Hayashi, Kaori","year":2026,"journal":"Diabetes, obesity & metabolism, 28(1), 701-710","doi":"10.1111/dom.70255","pmid":"41177923","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RA and SGLT2i prescribing in Japan is rising rapidly, with prescribing patterns increasingly differentiated by patient characteristics like age, BMI, and kidney function.","whyItMatters":"Tracking prescribing trends reveals how quickly evidence from clinical trials translates into practice and whether medications reach the patients who benefit most.","specificNumbers":"","methodology":"Retrospective analysis of a large-scale Japanese claims database (2015-2024); prescription rates assessed by drug class, stratified by multiple patient characteristics.","limitations":"Claims database — captures prescriptions but not adherence or clinical outcomes; Japanese prescribing patterns may not generalize to other healthcare systems."},{"rthcId":"RPEP-14778","title":"Cyclo-(His-Phe) Complexes with Copper and Zinc Nanoparticles Have Antimicrobial Properties and Targeted Anticancer Potential Against Osteosarcoma Cells.","authors":"Apostolidou, Chrysanthi Pinelopi; Charalambidis, Georgios; Gialouri, Aikaterini; Chatzinikolaidou, Maria; Mitraki, Anna","year":2026,"journal":"Biomolecules, 16(2)","doi":"10.3390/biom16020284","pmid":"41750355","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Cyclic peptide cyclo-(His-Phe) chelated copper and zinc nanoparticles demonstrated antimicrobial activity and selective anticancer effects against osteosarcoma cells.","whyItMatters":"Osteosarcoma has limited treatment options, and metal nanoparticles are promising but toxic. Peptide carriers could enable targeted delivery, reducing side effects.","specificNumbers":"","methodology":"Synthesis of cyclic peptide-metal nanoparticle complexes with characterization of self-assembly (amyloid-type fibrils) and evaluation of antimicrobial and anticancer activity in vitro.","limitations":"In vitro study only — no in vivo tumor model data; selectivity and safety in whole organisms untested."},{"rthcId":"RPEP-14779","title":"GLP-1-based therapeutics for cardiorenal protection in metabolic diseases.","authors":"Apperloo, Ellen M; Heerspink, Hiddo J L; van Raalte, Daniël H; Muskiet, Marcel H A","year":2026,"journal":"Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 41(2), 207-219","doi":"10.1093/ndt/gfaf110","pmid":"40560166","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RAs provide robust cardiorenal protection in metabolic diseases, with mounting evidence supporting their use beyond glycemic control.","whyItMatters":"Understanding GLP-1 RAs as cardiorenal protective agents — not just glucose-lowering drugs — is critical for optimal prescribing in patients with metabolic disease.","specificNumbers":"","methodology":"Narrative review synthesizing clinical trial data, real-world studies, and mechanistic evidence for GLP-1 RA cardiorenal benefits.","limitations":"Narrative review — selective literature coverage; primary cardiorenal endpoint data from dedicated kidney trials is still accumulating."},{"rthcId":"RPEP-14780","title":"The estrous cycle moderates the food and body weight suppressive effects of glucagon-like peptide-1 receptor agonism.","authors":"Applebey, Sarah V; Xiao, Allison G; Reiner, Benjamin C; Hayes, Matthew R","year":2026,"journal":"Diabetes, obesity & metabolism, 28(1), 221-230","doi":"10.1111/dom.70177","pmid":"41017581","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The estrous cycle moderates GLP-1 RA effects on food intake and body weight, with brainstem GLP-1 receptor expression varying across cycle phases.","whyItMatters":"If menstrual cycle phase affects GLP-1 drug efficacy in women, this could explain variable weight loss responses and potentially inform sex-specific dosing.","specificNumbers":"","methodology":"Preclinical study in female rats examining GLP-1 RA efficacy across estrous cycle phases, with brainstem gene expression analysis of Glp1r and Gcg.","limitations":"Animal model — rat estrous cycles are shorter and simpler than human menstrual cycles; direct translation to women needs clinical validation."},{"rthcId":"RPEP-14781","title":"Hydrogen bonding and membrane anchoring of the antimicrobial peptide NP-3a investigated through molecular dynamics.","authors":"Aquino, Ana Clara D; Mendanha, Karinna; Georg, Herbert de C; Colherinhas, Guilherme","year":2026,"journal":"Computational biology and chemistry, 123, 108997","doi":"10.1016/j.compbiolchem.2026.108997","pmid":"41780448","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"NP-3a transitions from ~23 intramolecular hydrogen bonds in compact form to ~122 water interactions in solution, then anchors to lipid membranes through specific hydrogen bonding patterns.","whyItMatters":"Understanding at the atomic level how antimicrobial peptides interact with membranes guides rational design of more effective peptide antibiotics.","specificNumbers":"","methodology":"Atomistic molecular dynamics simulations of NP-3a in three environments: vacuum, aqueous solution, and DOPC lipid bilayer interface.","limitations":"Computational simulation — predictions need experimental validation; DOPC bilayer is a simplified membrane model."},{"rthcId":"RPEP-14782","title":"Optimum Serum Concentration Enhances Migration of MDA-MB-231 Triple-Negative Breast Cancer Cells and Promotes Intracellular Delivery of Proapoptotic Domain via Cell-Penetrating Peptides.","authors":"Araki, Yurina; Takatani-Nakase, Tomoka; Ninomiya, Sohei; Matsumoto, Mitsuyo; Hirose, Hisaaki; Kawaguchi, Yoshimasa; Fujiwara, Daisuke; Michigami, Masataka; Katoh, Hironori; Wada, Takehiko; Futaki, Shiroh; Fujii, Ikuo; Hagiwara, Masaya; Nakase, Ikuhiko","year":2026,"journal":"Molecular pharmaceutics, 23(2), 730-742","doi":"10.1021/acs.molpharmaceut.5c00916","pmid":"41539681","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Serum concentration modulates TNBC cell migration, and cell-penetrating peptides successfully delivered proapoptotic cargo under optimized conditions.","whyItMatters":"TNBC has no targeted therapy options. CPP-delivered proapoptotic peptides could provide a new therapeutic approach for this deadly cancer subtype.","specificNumbers":"","methodology":"In vitro study using transwell migration assays with varying serum concentrations, followed by CPP-mediated intracellular delivery of proapoptotic peptide domain to MDA-MB-231 TNBC cells.","limitations":"In vitro study with one cell line — results may not generalize to all TNBC subtypes or in vivo tumors."},{"rthcId":"RPEP-14783","title":"Smart Healing for Wound Repair: Emerging Multifunctional Strategies in Personalized Regenerative Medicine and Their Relevance to Orthopedics.","authors":"Arciola, Carla Renata; Panichi, Veronica; Bua, Gloria; Costantini, Silvia; Bottau, Giulia; Ravaioli, Stefano; Capponi, Eleonora; Campoccia, Davide","year":2026,"journal":"Antibiotics (Basel, Switzerland), 15(1)","doi":"10.3390/antibiotics15010036","pmid":"41594073","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Multifunctional wound healing platforms integrating antimicrobial activity, tissue regeneration, immunomodulation, and real-time monitoring are emerging for personalized care.","whyItMatters":"Chronic wounds affect millions and cost healthcare systems billions. Smart, multifunctional approaches could dramatically improve outcomes, especially for high-risk surgical wounds.","specificNumbers":"","methodology":"Literature review of emerging wound healing technologies including natural/synthetic scaffolds, hydrogels with antimicrobial peptides, and smart monitoring systems.","limitations":"Review of emerging technologies — many are at early development stages; clinical translation timelines uncertain."},{"rthcId":"RPEP-14784","title":"Gut microbiota perturbation and systemic inflammation are associated with salcaprozate sodium (SNAC)-enabled oral semaglutide delivery.","authors":"Ariaee, Amin; Noueihad, Karim; Hunter, Alex; Wignall, Anthony; Wardill, Hannah R; Davies, Maya; Prestidge, Clive A; Joyce, Paul","year":2026,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 392, 114711","doi":"10.1016/j.jconrel.2026.114711","pmid":"41672308","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"SNAC absorption enhancer in oral semaglutide significantly disrupts gut microbiota and triggers systemic inflammation in rats, independent of semaglutide's effects.","whyItMatters":"If SNAC contributes to oral semaglutide's GI side effects, developing better absorption technologies could improve tolerability and reduce treatment discontinuation.","specificNumbers":"","methodology":"Preclinical study in Sprague Dawley rats over 21 days; three treatment groups (SEM, SNAC, SEM-SNAC) with microbiota analysis, metabolic profiling, and inflammatory marker assessment.","limitations":"Animal model — rat gut microbiome differs from human; 21-day duration may not capture long-term adaptation; SEM dose may not perfectly model human exposure."},{"rthcId":"RPEP-14785","title":"Patient Perceptions of Ozempic (Semaglutide) for Weight Loss: Mixed Methods Analysis of Online Medication Reviews.","authors":"Armanious, Abanoub J; Hunter, Rachel-Mae; Griffiths, Kristi R; Bowrey, Hannah E; Brown, Robyn M; James, Morgan H","year":2026,"journal":"Journal of medical Internet research, 28, e78391","doi":"10.2196/78391","pmid":"41512288","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Online reviews reveal that Ozempic users actively weigh weight loss benefits against GI side effects, with specific factors influencing satisfaction and continuation decisions.","whyItMatters":"Understanding real-world patient perceptions beyond clinical trials helps clinicians counsel patients about what to expect and addresses factors driving treatment discontinuation.","specificNumbers":"","methodology":"Mixed methods analysis of online medication reviews using infoveillance methodology; combining quantitative rating analysis with qualitative theme extraction.","limitations":"Self-selected online reviewers may not represent all users; potential for extreme-experience bias; no verification of medical details or dosing."},{"rthcId":"RPEP-14786","title":"BacA(SbmA) importer of legume symbiotic NCR peptides: Protein architecture, function, and evolutionary implications.","authors":"Arnold, Markus F F; Sankari, Siva; Deutsch, Michael; Gruber, Charley C; Guerra-Garcia, Francisco J; Beis, Konstantinos; Walker, Graham C","year":2026,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 123(7), e2526811123","doi":"10.1073/pnas.2526811123","pmid":"41665997","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BacA protein imports NCR antimicrobial peptides into the bacterial cytoplasm for proteolytic degradation, protecting symbiotic rhizobia during nitrogen fixation.","whyItMatters":"Understanding how bacteria survive antimicrobial peptides in symbiosis could inspire strategies for both enhancing beneficial symbioses in agriculture and overcoming bacterial resistance mechanisms.","specificNumbers":"","methodology":"Molecular biology and biochemistry study characterizing BacA protein architecture, NCR peptide import, and proteolytic degradation mechanisms.","limitations":"Focused on one bacterial species and its specific plant hosts; generalizability to other symbiotic systems needs investigation."},{"rthcId":"RPEP-14787","title":"Pharmacologic Treatments for the Preservation of Lean Body Mass During Weight Loss.","authors":"Arora, Gunjan; Conde, Katherine R; Desouza, Cyrus V","year":2026,"journal":"Journal of clinical medicine, 15(2)","doi":"10.3390/jcm15020541","pmid":"41598480","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Multiple pharmacological strategies are being investigated to preserve lean mass during obesity medication-induced weight loss, addressing a critical gap in current treatment.","whyItMatters":"Muscle loss during weight loss can undermine long-term health benefits. Finding effective lean mass preservation strategies is essential as millions use GLP-1 RAs.","specificNumbers":"","methodology":"Narrative review of emerging pharmacological approaches for lean body mass preservation during weight loss therapy.","limitations":"Review of emerging approaches — most preservation strategies are in early development with limited clinical data."},{"rthcId":"RPEP-14788","title":"IL2Pepscan: A machine learning framework for predicting IL-2 inducing peptides and their identification across global viral proteomes.","authors":"Arora, Pooja; Abhigyan, Rachit; Periwal, Neha; Agrawal, Lakshay; Sood, Vikas; Kaur, Baljeet","year":2026,"journal":"Scientific reports, 16(1), 6701","doi":"10.1038/s41598-026-35977-6","pmid":"41618087","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"IL2Pepscan accurately predicts IL-2-inducing peptides and identifies candidates across global viral proteomes for immunotherapy applications.","whyItMatters":"Faster identification of immune-stimulating peptides accelerates vaccine development, particularly for emerging viral threats.","specificNumbers":"","methodology":"Machine learning framework using pfeature, ifeature, and large language model-derived features; trained on IEDB peptide datasets; applied to viral proteome scanning.","limitations":"Computational predictions require experimental validation; training data quality limits prediction accuracy; not all IL-2-inducing peptides may be therapeutically useful."},{"rthcId":"RPEP-14789","title":"Real-world healthcare resource utilization and medical costs in patients with overweight or obesity and multimorbidity treated with semaglutide in the United States.","authors":"Arora, Prachi; Dabbous, Firas; Udayachalerm, Sariya; Saiontz-Martinez, Cynthia; Zhao, Zhenxiang; O Hartaigh, Briain; Fabricatore, Anthony; Bassan, Matthew; Alvarez, Sara; Fitch, Angela","year":2026,"journal":"Expert review of pharmacoeconomics & outcomes research, 26(2), 289-301","doi":"10.1080/14737167.2025.2610206","pmid":"41524543","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide users with overweight/obesity and multimorbidity had 27% lower total medical costs ($891 vs $1,213/month) compared to matched non-users.","whyItMatters":"Demonstrating cost savings strengthens the economic case for insurance coverage of obesity medications, which remains a major access barrier.","specificNumbers":"","methodology":"Retrospective propensity score-matched cohort study using Komodo Health claims database; patients with overweight/obesity and ≥2 obesity-related complications.","limitations":"Short follow-up (101 days); medication costs not included in comparison; healthy user bias possible despite matching; retrospective design."},{"rthcId":"RPEP-14790","title":"Resistant Hypertension: Integration of Novel Agents and Interventional Approaches in Clinical Practice.","authors":"Arriola-Montenegro, Jose; Chaponan-Lavalle, Andres; Nombera-Aznaran, Natalia; Abdalla, Mohammed; Bizer, Benjamin; Mohan, Arjunmohan; Muñoz Verdugo, Irma Andrea; Zardoost, Pooya; Ordaya-Gonzales, Karina; Villarreal Rizzo, Alan; Rios-Garcia, Wagner; Yip, Laverne Kar Yin; Gonzalez Suarez, Maria L","year":2026,"journal":"Reviews in cardiovascular medicine, 27(1), 45429","doi":"10.31083/RCM45429","pmid":"41659095","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Multiple novel therapeutic approaches for resistant hypertension are advancing, including RNA-based therapies, new mineralocorticoid antagonists, and device-based interventions.","whyItMatters":"Resistant hypertension affects millions and significantly increases cardiovascular risk. New therapeutic options are desperately needed for patients who don't respond to existing drugs.","specificNumbers":"","methodology":"Narrative review of emerging pharmacological and interventional therapies for resistant hypertension.","limitations":"Review of emerging therapies — many are in clinical trials without definitive outcome data; practical integration into clinical care not yet established."},{"rthcId":"RPEP-14791","title":"Innervation pattern of the anterolateral ligament (ALL) of the knee: Indication of an active role in proprioception and autonomic modulation.","authors":"Arviza-Lorenzo, P; Aragonés, P; Valderrama-Canales, F J; Schicht, M; Paulsen, F; Tschernig, T; Brockmeyer, M; Ruzik, K; Vázquez Osorio, M T","year":2026,"journal":"Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft, 263, 152732","doi":"10.1016/j.aanat.2025.152732","pmid":"40945874","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The ALL has extensive innervation with proprioceptive, nociceptive, and autonomic nerve fibers, suggesting active roles in knee position sensing and pain processing.","whyItMatters":"Understanding ALL innervation has implications for surgical reconstruction — procedures should consider preserving nerve supply for optimal proprioceptive recovery.","specificNumbers":"","methodology":"Immunohistochemistry (PGP9.5, VAChT markers) and electron microscopy analysis of 17 human ALL samples from adult body donors.","limitations":"Cadaveric study — cannot assess functional nerve activity; sample from older donors may not represent younger athletic populations."},{"rthcId":"RPEP-14792","title":"Evaluation of Antibodies Induced by Melanoma Helper Peptide Vaccine and Their Modulation by Vaccine Adjuvants.","authors":"Ashkani, Emily G; Dickinson, Anna M; Olson, Walter C; Taylor, Justin J; Slingluff, Craig L","year":2026,"journal":"Vaccines, 14(2)","doi":"10.3390/vaccines14020195","pmid":"41746115","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Six melanoma helper peptide vaccination induced tumor-specific antibodies with isotype distributions varying by adjuvant type.","whyItMatters":"Understanding how vaccine adjuvants influence antibody responses could optimize melanoma vaccine design for more effective anti-tumor immunity.","specificNumbers":"","methodology":"Analysis of antibody responses from clinical vaccination with 6MHP cocktail, comparing isotype profiles across different vaccine adjuvant formulations.","limitations":"Clinical vaccine study — sample sizes for adjuvant comparison may be limited; antibody detection does not confirm clinical benefit."},{"rthcId":"RPEP-14793","title":"A melanocortin 4- and glucagon-like peptide 1 receptor multiple agonist for the treatment of diabetes and obesity.","authors":"Ashlaw, Emily F; Elfers, Clinton T; Chichura, Kylie S; Miranda, Isabella Chavez; McGivney, Aelish; Chepurny, Oleg G; Holz, George G; Mullins, Ginger; den Hartigh, Laura J; Liu, Yongjun; Roth, Christian L; Doyle, Robert P","year":2026,"journal":"Metabolism: clinical and experimental, 174, 156414","doi":"10.1016/j.metabol.2025.156414","pmid":"41093057","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A monomeric peptide combining MC4 and GLP-1 receptor agonism showed enhanced weight loss and metabolic benefits with improved tolerability in preclinical models.","whyItMatters":"Better-tolerated obesity drugs are urgently needed, especially for children and adolescents. Dual MC4/GLP-1 targeting could provide a new pathway to effective, tolerable weight loss therapy.","specificNumbers":"","methodology":"Peptide design fusing α-MSH and Exendin-4 sequences, followed by in vitro receptor activation assays and in vivo metabolic studies in animal models.","limitations":"Preclinical data only — animal models may not predict human efficacy or tolerability; single peptide design challenges for manufacturing and stability."},{"rthcId":"RPEP-14794","title":"LL-37-derived peptide shows promising antimicrobial potential against multidrug-resistance pathogens.","authors":"Asmamaw, Demeke; Cai, Huajun; Prateeksha, Prateeksha; Khalid, Mehwish; Mwangi, James; Yi, Wang; Lu, Quimin; Lai, Ren; Duan, Zilei","year":2026,"journal":"European journal of medicinal chemistry, 304, 118547","doi":"10.1016/j.ejmech.2025.118547","pmid":"41485275","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Hybrid peptide KF-22, fusing snake and human cathelicidin fragments, demonstrated potent activity against multidrug-resistant Gram-positive and Gram-negative bacteria.","whyItMatters":"Multidrug-resistant infections kill over a million people annually. Novel peptide antibiotics designed from natural AMP fragments offer new therapeutic options.","specificNumbers":"","methodology":"Rational peptide design by fragment fusion (Cathelicidin-BF 1-9 + LL-37 17-29), followed by antimicrobial activity testing against MDR bacterial panels.","limitations":"In vitro testing only — in vivo efficacy, toxicity, and pharmacokinetics not yet established."},{"rthcId":"RPEP-14795","title":"Non-synaptically released oxytocin regulates social communication by acting on vasopressin V1a receptors.","authors":"Aspesi, Dario; Walton, James C; Grieb, Zachary A; Kirchner, Matthew K; Song, Zhimin; Long, Madeline R; Larkin, Tony E; Stern, Javier E; Albers, H Elliott","year":2026,"journal":"Journal of neuroendocrinology, 38(1), e70111","doi":"10.1111/jne.70111","pmid":"41249098","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Non-synaptically released oxytocin acts through vasopressin V1a receptors to regulate social communication (scent marking) in hamsters.","whyItMatters":"This challenges fundamental assumptions about neuropeptide signaling and reveals that oxytocin's effects on social behavior may be mediated through unexpected receptor pathways.","specificNumbers":"","methodology":"In vivo pharmacological study in Syrian hamsters examining scent marking behavior with manipulation of non-synaptic oxytocin release and receptor-specific antagonists.","limitations":"Hamster model — social communication mechanisms may differ in humans; scent marking is species-specific behavior."},{"rthcId":"RPEP-14796","title":"Glucagon-like peptide-1 receptor agonists and the risk of obesity-related cancers: a systematic review and meta-analysis.","authors":"Ateiwi, Yousef A; Mahmood, Rahil; Wong, Hon Jen; Low, Chen Ee; Yau, Chun En; Yan Bin Lee, Ainsley Ryan; Eng, Pei Chia; Lee, Matilda; Chan, Mark Y; Sia, Ching-Hui","year":2026,"journal":"Diabetes research and clinical practice, 113158","doi":"10.1016/j.diabres.2026.113158","pmid":"41722869","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RA use was associated with reduced risk of obesity-related cancers in patients with type 2 diabetes and/or obesity across combined RCT and observational evidence.","whyItMatters":"If GLP-1 RAs reduce cancer risk, this would be an enormous additional benefit beyond their metabolic effects, potentially preventing thousands of cancers annually.","specificNumbers":"","methodology":"Systematic review and meta-analysis; Embase, PubMed, and CENTRAL searched through November 2025; included RCTs and observational studies of adults with T2DM and/or obesity.","limitations":"Observational data subject to confounding; relatively short follow-up for cancer outcomes; weight loss itself may explain some cancer risk reduction."},{"rthcId":"RPEP-14797","title":"The promise of GLP-1 receptor agonists for neurodegenerative diseases.","authors":"Athauda, Dilan; Greig, Nigel H; Meissner, Wassilios G; Foltynie, Thomas; Gandhi, Sonia","year":2026,"journal":"The Journal of clinical investigation, 136(4)","doi":"10.1172/JCI194745","pmid":"41697753","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Preclinical and epidemiological evidence consistently supports GLP-1 RAs as neuroprotective agents across Alzheimer's, Parkinson's, and multiple sclerosis.","whyItMatters":"Neurodegenerative diseases have very limited treatment options. If GLP-1 RAs are truly neuroprotective, they could help millions of people with currently untreatable conditions.","specificNumbers":"","methodology":"Narrative review in The Journal of Clinical Investigation synthesizing preclinical mechanistic studies and epidemiological analyses.","limitations":"Most evidence is preclinical or epidemiological — dedicated RCTs for neurodegeneration are needed; translation from animal models to human disease is uncertain."},{"rthcId":"RPEP-14798","title":"Beyond molting disruption: Tebufenozide modifies gut immunity and antiviral responses in Helicoverpa armigera (Noctuidae).","authors":"Attarianfar, Marzieh; Mikani, Azam; Mehrabadi, Mohammad","year":2026,"journal":"Comparative biochemistry and physiology. Toxicology & pharmacology : CBP, 303, 110455","doi":"10.1016/j.cbpc.2026.110455","pmid":"41534733","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tebufenozide alters H. armigera gut immunity beyond molting disruption, inducing IMD pathway activation, AMP expression changes, and modified antiviral defense.","whyItMatters":"Understanding off-target immune effects of insecticides could reveal synergies or conflicts with biological control strategies used alongside chemical treatments.","specificNumbers":"","methodology":"RT-qPCR analysis of immune gene expression in H. armigera larvae exposed to lethal (LC₅₀) and sublethal (LC₁₀, LC₂₅) tebufenozide concentrations.","limitations":"Laboratory study — field conditions involve complex interactions; gene expression changes don't always translate to functional immune outcomes."},{"rthcId":"RPEP-14799","title":"Association of Glucagon-Like Peptide-1 Receptor Agonists and Suicidality: A Systematic Review.","authors":"Au, Hezekiah C T; Zheng, Yang Jing; Le, Gia Han; Wong, Sabrina; Teopiz, Kayla M; Kwan, Angela T H; Rosenblat, Joshua D; Mansur, Rodrigo B; Choi, Hayun; McIntyre, Roger S","year":2026,"journal":"Obesity reviews : an official journal of the International Association for the Study of Obesity, e70120","doi":"10.1111/obr.70120","pmid":"41792979","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Systematic review across multiple databases found no consistent evidence of increased suicidality associated with GLP-1 receptor agonist use.","whyItMatters":"With millions of patients on GLP-1 RAs and high-profile suicide reports generating fear, rigorous evidence reviews are essential for informed clinical decision-making.","specificNumbers":"","methodology":"Comprehensive systematic review searching OVID (Medline, EMBASE, AMED, PsycINFO, JBI), PubMed, and Web of Science through May 2024.","limitations":"Systematic review is only as good as the primary studies; most studies were not primarily designed to assess suicidality; underreporting of psychiatric events is possible."},{"rthcId":"RPEP-14800","title":"Personalized drug screening and risk assessment in patient-derived gastroenteropancreatic neuroendocrine neoplasms.","authors":"Auernhammer, Christoph J; Wang, Katharina; Maccio, Umberto; Knösel, Thomas; Hungbauer, Maximilian P; Schilbach, Katharina; Maurer, Julian; Peischer, Lea; Reul, Astrid; Kuzmenko, Elena; Luca, Edlira; Hamati, Julia; Vetter, Diana; Oberholzer, Jose; Fritsch, Ralph; Pacak, Karel; Grossman, Ashley B; Beuschlein, Felix; Reincke, Martin; Hantel, Constanze; Zitzmann, Kathrin; Nölting, Svenja","year":2026,"journal":"The Journal of clinical endocrinology and metabolism","doi":"10.1210/clinem/dgaf705","pmid":"41518601","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Personalized drug screening in patient-derived GEP-NEN cultures successfully identified individual tumor drug responses, demonstrating precision oncology feasibility.","whyItMatters":"Rare cancers like GEP-NENs lack the large trial data that guides treatment of common cancers. Personalized screening could match individual patients with their most effective therapy.","specificNumbers":"","methodology":"Standardized drug screening platform using 23 patient-derived GEP-NEN primary cultures (16/23 from metastatic tumors), testing responses to multiple therapeutic agents.","limitations":"Small sample (23 patients); primary cultures may not fully recapitulate in vivo tumor behavior; clinical correlation of in vitro drug sensitivity needs validation."},{"rthcId":"RPEP-14801","title":"Neuroimmune Activation in a Goat Model of Intervertebral Disc Degeneration.","authors":"Augustin, Janai A; Burt, Kevin G; Barrett, Caitlin; Fainor, Matthew; Orozco, Brianna S; Schaer, Thomas P; Smith, Harvey E; Mauck, Robert L; Gullbrand, Sarah E","year":2026,"journal":"Cells, 15(3)","doi":"10.3390/cells15030286","pmid":"41677649","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Disc degeneration in a goat model triggered neuroimmune activation with increased CGRP and substance P expression in degenerated discs and adjacent tissues.","whyItMatters":"Understanding the neuroimmune response to disc degeneration is essential for developing targeted therapies for discogenic back pain, which affects millions.","specificNumbers":"","methodology":"Large animal model using intradiscal chondroitinase ABC injection in goat cervical spine, with immunohistochemical assessment of disc pathology and neuroinflammatory markers.","limitations":"Chemical induction may not perfectly mimic natural age-related degeneration; goat cervical spine differs from human lumbar spine; relatively short follow-up."},{"rthcId":"RPEP-14802","title":"Signaling architecture of the glucagon-like peptide-1 receptor.","authors":"Austin, Gregory; Tomas, Alejandra","year":2026,"journal":"The Journal of clinical investigation, 136(2)","doi":"10.1172/JCI194752","pmid":"41542774","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The GLP-1R functions as an organizer of complex signaling nanodomains involving phase separation condensates and endosomal signaling beyond canonical cAMP activation.","whyItMatters":"Understanding GLP-1R signaling complexity could enable design of next-generation drugs that selectively activate beneficial pathways while avoiding side effect-causing pathways.","specificNumbers":"","methodology":"Comprehensive review of GLP-1R signaling mechanisms including signalosome assembly, biomolecular condensates, and intracellular signaling regulation.","limitations":"Review synthesizing cutting-edge research — some mechanisms are still being validated; therapeutic implications are theoretical."},{"rthcId":"RPEP-14803","title":"Beyond glycemic control: How incretins are changing the cardiovascular trajectories of diabetes and obesity.","authors":"Avogaro, Angelo","year":2026,"journal":"European journal of clinical investigation, 56(2), e70184","doi":"10.1111/eci.70184","pmid":"41653035","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Incretin-based therapies are fundamentally changing cardiovascular outcomes in diabetes and obesity through multiple protective mechanisms supported by strong clinical trial evidence.","whyItMatters":"Cardiovascular disease is the leading cause of death in diabetes and obesity. Incretins are among the first drug classes to meaningfully reduce this risk.","specificNumbers":"","methodology":"Comprehensive review consolidating cardiovascular evidence for incretin-based medications including preclinical mechanisms and clinical trial outcomes.","limitations":"Review — selective in coverage; cardiovascular outcome data for newest multi-agonists is still accumulating."},{"rthcId":"RPEP-14804","title":"Decreased risk of post-thyroidectomy hypocalcemia with history of GLP-1RA use.","authors":"Ayo-Ajibola, Oluwatobiloba; Jung, Tyler; Razura, Diego E; Gallagher, Tyler J; Lin, Matthew E; Angell, Trevor E; Kwon, Daniel I","year":2026,"journal":"Journal of the Endocrine Society, 10(1), bvaf204","doi":"10.1210/jendso/bvaf204","pmid":"41476725","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Prior GLP-1 RA/GIP-RA use was associated with decreased risk of hypocalcemia following total thyroidectomy in a propensity-matched analysis.","whyItMatters":"Post-thyroidectomy hypocalcemia causes significant morbidity. If GLP-1 RAs are protective, this could inform perioperative management for patients already on these medications.","specificNumbers":"","methodology":"Propensity-matched cohort study using TriNetX Platform (2010-2024); patients with GLP-1 RA/GIP-RA prescription within 1 year before total thyroidectomy vs. controls.","limitations":"Retrospective observational design; mechanism unclear; GLP-1 RA users may differ from non-users in unmeasured ways despite matching."},{"rthcId":"RPEP-14805","title":"New drug therapies for hypertension.","authors":"Azizi, Michel; Tuttle, Katherine R; Brown, Jenifer M; Piskorz, Daniel L; Kario, Kazuomi; Williams, Bryan","year":2026,"journal":"Lancet (London, England)","doi":"10.1016/S0140-6736(25)02064-1","pmid":"41687677","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Next-generation antihypertensives targeting novel pathways — including siRNA, endothelin antagonists, and GLP-1 RAs — show promise for improving global blood pressure control.","whyItMatters":"Hypertension is the world's leading modifiable cardiovascular risk factor, yet control rates remain unacceptably low. Novel drug classes could improve outcomes for millions.","specificNumbers":"","methodology":"Narrative review in The Lancet of emerging antihypertensive drug classes and their clinical evidence.","limitations":"Lancet review — comprehensive but most novel agents are in clinical trials without definitive long-term outcome data."},{"rthcId":"RPEP-14806","title":"SNAP-47 mediates somatic oxytocin dynamics in hypothalamic neurons.","authors":"Aznar-Escolano, Beatriz; Royo, Maria; Madrigal, Maria Pilar; Portalés Montes, Adrián; Villanueva, José; Gutiérrez, Luis Miguel; Jurado, Sandra","year":2026,"journal":"Communications biology, 9(1), 137","doi":"10.1038/s42003-025-09442-5","pmid":"41629537","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"SNAP-47 mediates somatodendritic oxytocin dynamics in hypothalamic neurons, representing novel molecular machinery for non-synaptic neuropeptide release.","whyItMatters":"Understanding how oxytocin is released from cell bodies (not just synapses) reveals mechanisms that could be targeted for treating social behavior disorders.","specificNumbers":"","methodology":"Molecular neuroscience study using mouse hypothalamus; SNAP-47 expression characterization, vesicle interaction analysis, and functional manipulation of oxytocin release dynamics.","limitations":"Mouse study — species differences in oxytocin signaling exist; behavioral implications of SNAP-47 manipulation need further investigation."},{"rthcId":"RPEP-14807","title":"Tyrosine-Peptide Analog Modulates Extracellular Vesicles miRNAs Cargo from Mesenchymal Stem/Stromal and Cancer Cells to Drive Immunoregeneration and Tumor Suppression.","authors":"B R G Ley, Michelle; Galoian, Karina; Martinez, Daniel A; Patel, Arianna; Thomas, Reanna; Parker, Tressa R; Friedman, Lee; Andryski, Allie L; Hornicek, Francis J; Best, Thomas M; Kouroupis, Dimitrios","year":2026,"journal":"Biomolecules, 16(2)","doi":"10.3390/biom16020243","pmid":"41750312","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"TPA treatment reprogrammed extracellular vesicle miRNA cargo from both stem cells and sarcoma cells, shifting intercellular communication toward immune activation and tumor suppression.","whyItMatters":"If a peptide can reprogram cancer cell communication to fight tumors rather than support them, this represents a novel therapeutic paradigm for hard-to-treat sarcomas.","specificNumbers":"","methodology":"EV isolation and characterization from IFP-MSCs and sarcoma cells with/without TPA treatment; miRNA profiling and pathway analysis.","limitations":"In vitro study — EV reprogramming in vivo may differ; functional anti-tumor effects need animal model validation."},{"rthcId":"RPEP-14808","title":"Injectable self-healing hydrogel loaded with a self-assembling LL-37 derivative for treating infected skin wounds.","authors":"Ba, Qi; Yao, Jiaxin; Tian, Hao; Meng, Yuanyuan; Kong, Yichen; Jia, Yongbo; Xu, Zhangshen; Yin, Shuhang; Gong, Wei; Wang, Yuli; Yang, Yang; Gao, Chunsheng; Yang, Meiyan","year":2026,"journal":"International journal of pharmaceutics, 692, 126653","doi":"10.1016/j.ijpharm.2026.126653","pmid":"41653943","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"FR-20 peptide loaded in self-healing hydrogel showed enhanced stability, sustained antimicrobial activity, and promoted healing in infected wound models.","whyItMatters":"Antimicrobial peptides lose activity quickly in wounds. A self-healing hydrogel that protects and sustainably releases the peptide could solve this problem for clinical wound care.","specificNumbers":"","methodology":"Rational peptide design (LL-37 derivative FR-20), self-healing hydrogel formulation via Schiff base cross-linking, and in vitro/in vivo wound healing evaluation.","limitations":"Preclinical study — clinical translation requires human safety and efficacy testing; manufacturing scalability untested."},{"rthcId":"RPEP-14809","title":"Probing the Effect of α-Helical Stapling Strategies on the Inhibition of Peptide Aggregation and Amyloid Cytotoxicity.","authors":"Babych, Margaryta; Nguyen, Phuong Trang; Bérubé, Frédérique; Bourgault, Steve","year":2026,"journal":"ACS chemical biology, 21(1), 96-106","doi":"10.1021/acschembio.5c00685","pmid":"41486923","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"α-Helical stapling effectively prevents IAPP peptide aggregation and amyloid-associated cytotoxicity, with efficacy varying by stapling strategy.","whyItMatters":"Amyloid deposits contribute to beta cell death in diabetes. Strategies preventing IAPP aggregation could lead to disease-modifying therapies and more stable peptide drugs.","specificNumbers":"","methodology":"Systematic study of multiple stapling (side chain-to-side chain macrocyclization) strategies on IAPP derivatives; aggregation, toxicity, and structural analysis.","limitations":"In vitro study — stapled peptide behavior in vivo (in the pancreas) may differ; manufacturing complexity of stapled peptides."},{"rthcId":"RPEP-14810","title":"Body composition, hepatic fat, metabolic, and safety outcomes of Tesamorelin, a GHRH analogue, in HIV-associated lipodystrophy: A meta-analysis of randomized controlled trials.","authors":"Badran, Ahmed Samy; Helal, Abdulrhman; Shata, Karim Samir; Ayesh, Hazem","year":2026,"journal":"Obesity research & clinical practice, 20(1), 2-12","doi":"10.1016/j.orcp.2026.01.002","pmid":"41545261","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tesamorelin significantly reduces visceral and hepatic fat in HIV-associated lipodystrophy versus placebo across randomized controlled trials.","whyItMatters":"HIV-associated lipodystrophy causes significant morbidity and cardiovascular risk. Tesamorelin provides targeted therapy for a condition with few effective treatments.","specificNumbers":"","methodology":"Systematic review and random-effects meta-analysis of RCTs evaluating tesamorelin vs. placebo in adults with HIV; PubMed, Embase, Scopus, Web of Science, CENTRAL searched through July 2025.","limitations":"Limited number of available RCTs; mostly short to medium-term follow-up; HIV-specific population limits generalizability."},{"rthcId":"RPEP-14811","title":"Semaglutide for the treatment of cognitive dysfunction in major depressive disorder: A randomized clinical trial.","authors":"Badulescu, Sebastian; Gill, Hartej; Shah, Hiya; Brudner, Ryan; Phan, Lee; Di Vincenzo, Joshua D; Tabassum, Aniqa; Armanyous, Michael; Llach, Cristian-Daniel; Rosenblat, Joshua D; McIntyre, Roger S; Mansur, Rodrigo B","year":2026,"journal":"Med (New York, N.Y.), 7(1), 100916","doi":"10.1016/j.medj.2025.100916","pmid":"41218611","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide significantly improved cognitive dysfunction in overweight/obese adults with major depressive disorder in a 16-week randomized clinical trial.","whyItMatters":"This is landmark evidence — the first RCT showing a GLP-1 RA improves cognition in depression. Cognitive dysfunction is one of the most disabling aspects of depression and lacks targeted treatments.","specificNumbers":"","methodology":"16-week randomized, double-blind, placebo-controlled, parallel-group trial (NCT04466345); overweight/obese adults with DSM-5 MDD and cognitive impairment.","limitations":"Participants were overweight/obese — unclear if cognitive benefits extend to normal-weight depression patients; relatively short 16-week duration; adjunctive therapy (added to existing treatment)."},{"rthcId":"RPEP-14812","title":"Bicyclic peptide-based CPPTACs for extracellular and cell membrane protein degradation.","authors":"Bai, Jinyu; Shi, Huaihuai; Chen, Jitun; Tian, Hui; Liang, Jiaxin; Chen, Bichun; Li, Jiazhong; Fang, Lijing","year":2026,"journal":"Bioorganic & medicinal chemistry letters, 132, 130496","doi":"10.1016/j.bmcl.2025.130496","pmid":"41371309","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Bicyclic CPPTACs selectively degrade extracellular and cell surface proteins through CPP-induced endocytosis and lysosomal delivery.","whyItMatters":"Targeted protein degradation is revolutionizing drug development, but most technologies only work on intracellular proteins. CPPTACs extend this approach to the much larger pool of extracellular targets.","specificNumbers":"","methodology":"Peptide chemistry: conjugation of bicyclic CPP (KRK motif) with target-binding elements; demonstration of endocytosis-mediated protein degradation.","limitations":"Early-stage proof-of-concept; in vivo stability, selectivity, and safety need extensive testing; manufacturing of bicyclic peptide conjugates may be complex."},{"rthcId":"RPEP-14813","title":"Neuronal pentraxin 2 in peripheral sensory neurons drives chronic itch through potentiation of the interleukin-31/interleukin-31 receptor pathway in atopic dermatitis.","authors":"Bai, Xue-Qiang; Wu, Bing-Xin; Wang, Ji-An; He, Cheng; Shen, Yong-Liang; Wei, Xiao; Zhang, Yu-Qi; Chen, Xue-Wen; Sun, Rong; Gui, Qun-Feng; Wang, Juan; Zhang, Zhi-Jun","year":2026,"journal":"International immunopharmacology, 172, 116223","doi":"10.1016/j.intimp.2026.116223","pmid":"41564473","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"NPTX2 in peripheral sensory neurons amplifies IL-31/IL-31R-mediated chronic itch in atopic dermatitis, representing a novel therapeutic target.","whyItMatters":"Chronic itch devastates quality of life in eczema. Identifying NPTX2 as a new driver of itch signaling opens a novel target for anti-itch therapies.","specificNumbers":"","methodology":"Multi-technique study: RT-qPCR, immunohistochemistry, ELISA, western blot, and siRNA knockdown in AD models to characterize NPTX2's role in itch signaling.","limitations":"Preclinical study — NPTX2's role in human AD-associated itch needs clinical validation; therapeutic targeting strategies not yet developed."},{"rthcId":"RPEP-14814","title":"An Amphibious Fish-Derived Antimicrobial Peptide, Boleokidin39-61, with Broad-Spectrum Antibacterial Activity and In Vivo Protective Efficacy.","authors":"Bai, Yuqi; Zhan, Jingyuan; Zhang, Weibin; Zheng, Wenbin; Chen, Fangyi; Wang, Ke-Jian","year":2026,"journal":"Journal of natural products","doi":"10.1021/acs.jnatprod.5c01507","pmid":"41736391","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Boleokidin39-61 exhibited broad-spectrum antibacterial activity including against MDR strains, with confirmed in vivo protective efficacy in fish.","whyItMatters":"Discovering multiple effective AMPs from the same fish species builds a toolkit of peptide alternatives to antibiotics for aquaculture disease management.","specificNumbers":"","methodology":"Gene expression analysis in infected mudskipper, peptide synthesis, broad-spectrum antimicrobial testing, and in vivo fish infection protection studies.","limitations":"Aquaculture-focused; human therapeutic potential not explored; production scaling challenges."},{"rthcId":"RPEP-14815","title":"Pecbloodin18-37: a promising antimicrobial peptide from Boleophthalmus pectinirostris with therapeutic potential against Edwardsiella tarda infection.","authors":"Bai, Yuqi; Zheng, Wenbin; Zhang, Weibin; Zhan, Jingyuan; Chen, Fangyi; Wang, Ke-Jian","year":2026,"journal":"Applied and environmental microbiology, e0204325","doi":"10.1128/aem.02043-25","pmid":"41728968","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Pecbloodin18-37 from mudskipper showed potent antimicrobial activity against E. tarda including MDR strains, with in vivo protective efficacy.","whyItMatters":"Aquaculture antibiotic resistance threatens global food security. Fish-derived antimicrobial peptides offer species-relevant alternatives to conventional antibiotics.","specificNumbers":"","methodology":"Gene identification from mudskipper transcriptome, peptide synthesis and antimicrobial testing, and in vivo infection protection studies.","limitations":"Aquaculture-focused — applicability to human medicine not established; production scalability for aquaculture use untested."},{"rthcId":"RPEP-14816","title":"The genetic fusion of thaumatin-like proteins with antimicrobial peptides or receptor-like kinases at different evolutionary time points contributes to plant resistance against Sclerotinia disease.","authors":"Bai, Zetao; He, Yizhou; Huang, Junyan; Zhong, Xue; Shi, Meijuan; Zuo, Rong; Tang, Minqiang; Xie, Meili; Gao, Feng; Tong, Chaobo; Liu, Lijiang; Liu, Shengyi","year":2026,"journal":"Plant physiology and biochemistry : PPB, 231, 111065","doi":"10.1016/j.plaphy.2026.111065","pmid":"41576508","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Gene fusions between TLPs and AMPs/RLKs at different evolutionary timepoints created novel defense proteins that enhance rapeseed resistance against Sclerotinia disease.","whyItMatters":"Understanding how plants naturally evolved enhanced immune defenses through gene fusion could inform breeding and engineering strategies for crop disease resistance.","specificNumbers":"","methodology":"Evolutionary analysis of gene fusion events in rapeseed, dating fusion timepoints and characterizing the disease resistance function of fusion proteins.","limitations":"Focused on rapeseed — generalizability to other crops needs investigation; mechanistic details of how fusion proteins enhance resistance need further study."},{"rthcId":"RPEP-14817","title":"Temperature-responsive hydrogel delivery of antimicrobial peptide engineered watermelon-derived extracellular vesicles enables sequential infection control and wound healing.","authors":"Bai, Ziyang; Zhao, Yifan; Gong, Yajuan; Du, Meijun; Zhang, Wenjun; Zhang, Ke; Zhi, Yongchao; Nie, Yanan; Li, Xia; Wu, Xiuping; Li, Bing","year":2026,"journal":"Colloids and surfaces. B, Biointerfaces, 261, 115438","doi":"10.1016/j.colsurfb.2026.115438","pmid":"41544522","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"AMP-engineered watermelon vesicles in temperature-responsive hydrogel provided sequential infection control followed by wound healing promotion.","whyItMatters":"Combining plant-derived vesicles with AMPs in smart hydrogels creates a multifunctional wound treatment that addresses multiple healing challenges simultaneously.","specificNumbers":"","methodology":"Synthesis of AMP-conjugated watermelon-derived EVs; incorporation into temperature-responsive hydrogel; in vitro antimicrobial testing and wound healing assessment.","limitations":"Preclinical study — clinical translation requires extensive safety and efficacy testing; watermelon EV production standardization needed."},{"rthcId":"RPEP-14818","title":"The Metabolic Heart: Reframing Heart Failure With Preserved Ejection Fraction as a Systemic Cardio-Metabolic Syndrome.","authors":"Baidya, Debasrita; Hanumanpratap Singh Kshatri, Abhishek; Zerzan, Emi K; Menon, Gayathri J; Sawale, Mihika; Subhash Bhalodiya, Sunny","year":2026,"journal":"Cureus, 18(1), e100590","doi":"10.7759/cureus.100590","pmid":"41635389","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"HFpEF is better understood as a systemic cardio-metabolic disorder where GLP-1 RAs and SGLT2 inhibitors show benefit by targeting underlying metabolic dysfunction rather than neurohormonal pathways.","whyItMatters":"HFpEF affects millions and has historically had no effective treatment. Reconceptualizing it as a metabolic disease finally provides a rational treatment framework.","specificNumbers":"","methodology":"Systematic search of PubMed, Scopus, and Web of Science (2000-2025); 108 studies selected from ~800 screened; RCTs, cohorts, and mechanistic reports.","limitations":"Review — while comprehensive, the metabolic framework may oversimplify HFpEF heterogeneity; not all HFpEF patients have metabolic phenotype."},{"rthcId":"RPEP-14819","title":"Long-acting amylin-related peptides as therapies for obesity and type 2 diabetes.","authors":"Bailey, Clifford J; Flatt, Peter R; Conlon, J Michael","year":2026,"journal":"Peptides, 196, 171480","doi":"10.1016/j.peptides.2026.171480","pmid":"41747885","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Second-generation non-aggregating, long-acting amylin analogues are advancing in clinical development, offering improved dosing convenience over pramlintide.","whyItMatters":"Amylin signaling is a key therapeutic target for next-generation obesity and diabetes drugs, complementary to GLP-1-based approaches.","specificNumbers":"","methodology":"Narrative review of amylin biology, receptor structure, peptide design principles, and clinical development of second-generation amylin analogues.","limitations":"Review of emerging therapies — most second-generation agents are still in clinical trials; long-term safety data pending."},{"rthcId":"RPEP-14820","title":"Pharmacological therapies for type 2 diabetes: future approaches.","authors":"Bailey, Clifford J","year":2026,"journal":"Diabetologia, 69(1), 20-35","doi":"10.1007/s00125-025-06581-6","pmid":"41174263","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Multiple novel diabetes therapies targeting new pathways are in development, aiming to improve glycemic control while avoiding hypoglycemia and supporting weight loss.","whyItMatters":"Despite current options, many patients have inadequately controlled diabetes. Next-generation therapies could fill remaining treatment gaps.","specificNumbers":"","methodology":"Narrative review of non-insulin diabetes therapies in early clinical development, published in Diabetologia.","limitations":"Review of early-stage therapies — most have not completed phase 3 trials; ultimate clinical utility uncertain."},{"rthcId":"RPEP-14821","title":"Contemporary management of advanced chronic kidney disease: An evidence-based review.","authors":"Baker, Lyle W; Ovincy, Cene; Souvalian, Levon; Hickson, LaTonya J; Chebib, Fouad T","year":2026,"journal":"European journal of internal medicine, 143, 106557","doi":"10.1016/j.ejim.2025.106557","pmid":"41130867","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"SGLT2 inhibitors and GLP-1 RAs have transformed CKD management with cardiorenal benefits beyond glucose control, alongside emerging therapies targeting novel pathways.","whyItMatters":"CKD is a leading cause of death worldwide. The therapeutic revolution driven by metabolic drugs is improving outcomes for millions of patients.","specificNumbers":"","methodology":"Evidence-based narrative review of contemporary CKD therapeutics published in European Journal of Internal Medicine.","limitations":"Narrative review — selective coverage; some emerging therapies lack mature clinical outcome data."},{"rthcId":"RPEP-14822","title":"Investigating the Link Between Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists and Non-arteritic Ischemic Optic Neuropathy: A Case Report of Semaglutide-Induced Optic Neuropathy.","authors":"Bakheet, Mashair; Chaudhary, Attiqa","year":2026,"journal":"Cureus, 18(1), e102472","doi":"10.7759/cureus.102472","pmid":"41769577","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"NAION in a young diabetic patient on semaglutide completely resolved after GLP-1 RA discontinuation, adding to emerging NAION-GLP-1 RA association concerns.","whyItMatters":"NAION can cause permanent vision loss. If GLP-1 RAs increase NAION risk, millions of users should be aware and monitored, especially those with pre-existing risk factors.","specificNumbers":"","methodology":"Case report with clinical ophthalmological documentation and follow-up after semaglutide discontinuation.","limitations":"Single case report — cannot establish causation; diabetes itself is a NAION risk factor; spontaneous NAION resolution can occur."},{"rthcId":"RPEP-14823","title":"The Neuro-Bone Axis in Metastatic Progression: Innervation, Neuro-Immune-Osteoclast Crosstalk, and Therapeutic Opportunities.","authors":"Bakir, Mohamad; Dabaliz, Alhomam; Raddaoui, Mohammed; Fatash, Hala; Elsaadany, Nourhan; AlKattan, Wael; Mohammad, Khalid Said","year":2026,"journal":"Biology, 15(4)","doi":"10.3390/biology15040364","pmid":"41744673","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Neuropeptides such as substance P and CGRP exert dual effects on bone-remodeling cells and immune populations, directly shaping the metastatic niche that allows cancer cells to grow in bone.","whyItMatters":"Understanding how neuropeptides influence the bone microenvironment could lead to new combination therapies that disrupt neural support for metastatic cancer, potentially improving outcomes for patients with bone metastases.","specificNumbers":"","methodology":"Narrative review synthesizing preclinical and clinical evidence on bone innervation, tumor-induced neural remodeling, and neuro-immune-osteoclast interactions in bone metastasis.","limitations":"As a narrative review, it does not provide new experimental data. Many of the proposed therapeutic strategies are based on preclinical models, and the spatial mapping of nerve-tumor interfaces in humans remains incomplete."},{"rthcId":"RPEP-14824","title":"Concurrent diabetes and heart failure: revisiting epidemiological and clinicopathological interplay.","authors":"Balagopalan, Jayagopal Pathiyil; Bansal, Sandeep; Bhattacharyya, Arpandev; Zargar, Abdul Hamid; Dani, Sameer; Taraphder, Abhijit; Almeida, Alan; Deka, Nilakshi; Jain, Sanjay; Swami, Onkar C","year":2026,"journal":"Diabetology international, 17(1), 12","doi":"10.1007/s13340-025-00855-5","pmid":"41476907","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Diabetes and heart failure have a bidirectional pathophysiological relationship where each condition actively promotes and worsens the other.","whyItMatters":"With both conditions rising globally, understanding their mutual reinforcement is critical for developing effective treatment strategies that address both simultaneously.","specificNumbers":"","methodology":"Narrative review of the epidemiological, mechanistic, and clinical interplay between diabetes mellitus and heart failure.","limitations":"Narrative review — comprehensive but selective; the complexity of bidirectional pathophysiology makes specific therapeutic recommendations difficult."},{"rthcId":"RPEP-14825","title":"The impact of GLP-1 and incretin-based therapies on counterregulatory responses to hypoglycemia in diabetes mellitus: mechanisms and clinical implications.","authors":"Balakumar, Pitchai; Khan, Noohu Abdulla; Easwaran, Vigneshwaran; Orayj, Khalid M","year":2026,"journal":"Diabetes research and clinical practice, 233, 113155","doi":"10.1016/j.diabres.2026.113155","pmid":"41692324","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Evidence suggests elevated GLP-1 and incretin-based therapies may impair counterregulatory responses to hypoglycemia, particularly in patients with pre-existing hypoglycemia unawareness.","whyItMatters":"Hypoglycemia unawareness is dangerous and can cause seizures, coma, or death. Understanding whether GLP-1 drugs affect counterregulation is a critical safety question.","specificNumbers":"","methodology":"Narrative review synthesizing preclinical and clinical evidence on GLP-1/incretin effects on hypoglycemia counterregulation.","limitations":"Much evidence from animal models; clinical data in humans is limited; mechanisms may differ between type 1 and type 2 diabetes."},{"rthcId":"RPEP-14826","title":"Modulation of circulating extracellular vesicles by antihyperglycemic therapies: A pilot randomized controlled trial.","authors":"Baldassarre, Maria Pompea Antonia; Carrieri, Federica; Coluzzi, Sara; D'Ascanio, Francesca; Di Pietrantonio, Nadia; Centorame, Giorgia; Pipino, Caterina; Lanuti, Paola; Consoli, Agostino; Formoso, Gloria","year":2026,"journal":"Journal of diabetes and its complications, 40(3), 109273","doi":"10.1016/j.jdiacomp.2026.109273","pmid":"41621217","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Liraglutide, empagliflozin, and gliclazide produced distinct changes in circulating extracellular vesicle subpopulations in T2D, potentially reflecting different vascular effects.","whyItMatters":"EVs may explain how different diabetes drugs protect (or fail to protect) blood vessels. This could eventually guide drug selection based on vascular biomarkers.","specificNumbers":"","methodology":"Single-center pilot randomized controlled trial; 60 T2DM patients + 20 healthy controls; EV concentration and subpopulation profiling pre- and post-treatment.","limitations":"Pilot study with small sample per arm; short-term treatment; EV measurement methodology still being standardized; clinical significance of EV changes uncertain."},{"rthcId":"RPEP-14827","title":"Inflammation suppressing activity of jellyfish toxin-derived peptide via downregulation of ROS/NF-κB/NLRP3 signaling in LPS/MSU induced fibroblasts in vitro and in vivo gouty arthritis model.","authors":"Balde, Akshad; Nazeer, Rasool Abdul","year":2026,"journal":"Inflammopharmacology","doi":"10.1007/s10787-026-02108-6","pmid":"41656470","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Jellyfish toxin-derived peptide suppressed gouty arthritis inflammation by downregulating ROS/NF-κB/NLRP3 signaling in vitro and in vivo.","whyItMatters":"Gout treatment options have significant limitations. Marine venom-derived peptides could provide novel anti-inflammatory agents targeting the inflammasome pathway.","specificNumbers":"","methodology":"Integrated computational-experimental approach: PeptideRanker, ToxinPred, SwissADME, molecular docking, followed by in vitro (LPS/MSU-stimulated fibroblasts) and in vivo gouty arthritis model testing.","limitations":"Early-stage study — toxicity, bioavailability, and pharmacokinetics need extensive investigation; clinical translation is distant."},{"rthcId":"RPEP-14828","title":"Unmasking an insulinoma: recurrent Hypoglycemia in a young patient following GLP-1 receptor agonist therapy -A case report.","authors":"Baldera-Rodriguez, Nicole; Simo-Campillo, Natasha; Sanrregre-Oven, Patricia; Lopez, Enrique Capellan; Romano, Ramon; Goicochea, Anahi B","year":2026,"journal":"Oxford medical case reports, 2026(1), omaf283","doi":"10.1093/omcr/omaf283","pmid":"41589102","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide unmasked a previously undetected insulinoma in a young woman, presenting as severe refractory hypoglycemia requiring investigation.","whyItMatters":"As GLP-1 RAs are increasingly prescribed to young adults for weight loss, clinicians must recognize that unexplained severe hypoglycemia warrants investigation for insulinoma.","specificNumbers":"","methodology":"Case report with detailed clinical documentation including blood glucose (35 mg/dL), insulin (77.5 mU/L), C-peptide, and response to treatment.","limitations":"Single case — rare circumstance; the frequency of insulinoma unmasking by GLP-1 RAs is unknown."},{"rthcId":"RPEP-14829","title":"Preserved Ejection, Lost Rhythm: A Narrative Review of the Pathophysiology and Management of Heart Failure with Preserved Ejection Fraction and Concomitant Atrial Fibrillation.","authors":"Ballatore, Andrea; Poggio, Alan; Sullivan, Andrew P; Saglietto, Andrea; De Ferrari, Gaetano Maria; Anselmino, Matteo","year":2026,"journal":"Journal of clinical medicine, 15(3)","doi":"10.3390/jcm15030969","pmid":"41682651","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"HFpEF and AF coexist in 40-60% of cases, mutually worsening each other through adverse remodeling, with emerging metabolic therapies offering new management options.","whyItMatters":"The HFpEF-AF combination affects millions and significantly worsens outcomes. Integrated management strategies are needed but evidence is limited.","specificNumbers":"","methodology":"Narrative review of HFpEF-AF pathophysiology, diagnostic challenges, and evidence-based management strategies.","limitations":"Narrative review — limited by the sparse evidence specifically addressing the HFpEF-AF overlap population."},{"rthcId":"RPEP-14830","title":"The effect of glucagon-like peptide 1 (GLP-1) receptor agonists on cognition: A systematic review of systematic reviews and meta-analyses.","authors":"Ballum, Hana; Dri, Christine; Liao, Sonya; Yu, Minyi; Le, Gia Han; Wong, Sabrina; Teopiz, Kayla M; Kwan, Angela T H; Ho, Roger; Choi, Hayun; Rosenblat, Joshua D; Vinberg, Maj; K Y Lo, Heidi; McIntyre, Roger S","year":2026,"journal":"Journal of affective disorders, 402, 121310","doi":"10.1016/j.jad.2026.121310","pmid":"41621451","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Available systematic reviews suggest GLP-1 RAs may have cognitive benefits in people with T2DM and cognitive impairment, though evidence remains limited.","whyItMatters":"With millions of diabetic patients at cognitive risk, any proven cognitive benefit of GLP-1 RAs — which they're already taking — would have enormous public health impact.","specificNumbers":"","methodology":"Systematic review of systematic reviews and meta-analyses; Web of Science and MEDLINE searched through July 2025; three independent reviewers.","limitations":"Umbrella review limited by quality of included reviews; primary studies often small with heterogeneous cognitive measures; publication bias possible."},{"rthcId":"RPEP-14831","title":"Acute peripheral versus central inhibition of insulin receptors differentially alters cytokine and blood-brain barrier responses to an inflammatory stimulus.","authors":"Bandarupalli, Tanmai; Noonan, Cassidy; Hansen, Kim; Weaver, Riley; Baumann, Kristen; Banks, William A; Erickson, Michelle A; Rhea, Elizabeth M","year":2026,"journal":"Brain, behavior, and immunity, 133, 106251","doi":"10.1016/j.bbi.2025.106251","pmid":"41478465","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Peripheral and central insulin receptor inhibition produce distinct cytokine and BBB responses to inflammation, suggesting location-specific mechanisms linking insulin resistance to neurodegeneration.","whyItMatters":"Understanding whether peripheral or central insulin resistance drives BBB disruption could guide therapeutic strategies for preventing neurodegeneration in metabolic disease.","specificNumbers":"","methodology":"Preclinical study examining acute peripheral vs. central insulin receptor blockade followed by inflammatory challenge, with measurement of cytokine profiles and BBB integrity.","limitations":"Acute insulin receptor blockade may not perfectly model chronic insulin resistance; animal model; translational relevance to human conditions needs validation."},{"rthcId":"RPEP-14832","title":"From Neoantigen Discovery to Immune-Checkpoint Synergy: Peptide Cancer Vaccines as Precision Tools for Personalised Cancer Therapy.","authors":"Banday, Abid H; Manzoor, Meer Mehru; Nissar, Urooj; Jaleel, Seeham","year":2026,"journal":"Scandinavian journal of immunology, 103(1), e70084","doi":"10.1111/sji.70084","pmid":"41521168","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Peptide cancer vaccines combined with immune checkpoint inhibitors show enhanced anti-tumor responses, representing a promising personalized oncology approach.","whyItMatters":"Peptide vaccines could provide personalized, non-invasive cancer treatment that activates the patient's own immune system against their specific tumor.","specificNumbers":"","methodology":"Comprehensive review of peptide cancer vaccine development, neoantigen identification, and immune checkpoint synergy strategies.","limitations":"Review — many combinations are in early clinical trials; manufacturing personalized vaccines is complex and expensive; not all tumor types are equally amenable."},{"rthcId":"RPEP-14833","title":"Combined Glucagon-Like Peptide-1 Receptor Agonist (GLP-1RA) and Sodium-Glucose Cotransporter 2 Inhibitor (SGLT2i) Therapy to Restore Fertility in Patients With Obesity, Polycystic Ovary Syndrome, and Incident Type 2 Diabetes.","authors":"Banerjee, Mainak; Dasgupta, Sujoy","year":2026,"journal":"Cureus, 18(1), e102358","doi":"10.7759/cureus.102358","pmid":"41769480","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Combined GLP-1 RA/SGLT2i therapy produced rapid weight loss, menstrual normalization, and spontaneous conception within 7 months in two obese women with PCOS and T2D.","whyItMatters":"PCOS-related subfertility with obesity and diabetes is common. If metabolic optimization with readily available drugs can restore fertility, it could reduce the need for expensive fertility treatments.","specificNumbers":"","methodology":"Case report of two patients treated with combined GLP-1 RA and SGLT2i for PCOS with obesity and new-onset T2D.","limitations":"Two case reports — cannot establish treatment protocol; spontaneous pregnancy could be coincidental; GLP-1 RAs and SGLT2i are not approved for use during pregnancy."},{"rthcId":"RPEP-14834","title":"Histological efficacy of anti-diabetic agents in MASH and the mediating role of weight loss: A network meta-analysis.","authors":"Banerjee, Mainak; Pal, Rimesh; Pal, Sandip","year":2026,"journal":"Diabetes, obesity & metabolism, 28(1), 287-295","doi":"10.1111/dom.70187","pmid":"41063381","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RAs and pioglitazone showed the greatest histological improvement in MASH, with weight loss mediating a significant portion of fibrosis benefit.","whyItMatters":"MASH is becoming a leading cause of liver transplantation. Identifying which diabetes drugs best improve liver histology could prevent progression to cirrhosis in millions.","specificNumbers":"","methodology":"Frequentist random-effects network meta-analysis of biopsy-confirmed MASH trials; primary outcome: fibrosis improvement; dose-response and weight loss mediation analyzed.","limitations":"Network meta-analysis relies on indirect comparisons; included trials had varying durations and populations; biopsy-based outcomes have sampling variability."},{"rthcId":"RPEP-14835","title":"Membrane-Mimetic Micelles Drive Structural Switching in Uperin 3.5.","authors":"Banerjee, Sucharita; Prasad, Anup Kumar; Martin, Lisandra L; Panwar, Ajay Singh","year":2026,"journal":"The journal of physical chemistry. B, 130(2), 677-689","doi":"10.1021/acs.jpcb.5c05659","pmid":"41481806","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Uperin 3.5 undergoes rapid α-helix to β-sheet conformational switching near zwitterionic micelle surfaces within microsecond timescales, driven by membrane-peptide interactions.","whyItMatters":"Understanding how antimicrobial peptides switch conformations at membrane surfaces could guide the design of new peptide-based antibiotics and help explain the evolutionary link between antimicrobial defense and amyloid formation.","specificNumbers":"","methodology":"Microsecond-scale molecular dynamics simulations of Uperin 3.5 near DPC micelles, analyzing conformational transitions and self-assembly behavior.","limitations":"Computational study only — no experimental validation of the predicted conformational transitions. Simulations used simplified membrane mimics rather than full biological membranes."},{"rthcId":"RPEP-14836","title":"The association of GLP-1 receptor agonists and outcomes following midfoot arthrodesis.","authors":"Bank, Nicholas C; Lauck, Bradley J; Dalola, Joseph; Duggan, Sam; Dyke, William B; Lalli, Trapper A","year":2026,"journal":"The Journal of foot and ankle surgery : official publication of the American College of Foot and Ankle Surgeons","doi":"10.1053/j.jfas.2026.01.011","pmid":"41565054","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Perioperative GLP-1 receptor agonist use was associated with comparable or improved outcomes following midfoot arthrodesis in propensity-matched patients.","whyItMatters":"As more surgical patients use GLP-1 medications, surgeons need to know whether to continue or stop these drugs around surgery. This data supports continued use during midfoot procedures.","specificNumbers":"","methodology":"Retrospective cohort study using the TriNetX US Collaborative Network with 1:1 propensity score matching for demographic and clinical variables.","limitations":"Retrospective design limits causal conclusions. Database studies may have coding errors and cannot capture all confounding variables like compliance and exact timing of medication use."},{"rthcId":"RPEP-14837","title":"Insulin-like peptide 5 is released in response to bile acid in the rectum and is associated with diarrhoea severity in patients with bile acid diarrhoea.","authors":"Bannon, Christopher A; Walters, Julian R F; Wu, Tongzhi; Kay, Richard G; Punnoose, Austin; Spiller, Robin C; Wilson, Jonathan; Verdino, Petra; Barker, Peter; Burling, Keith; Horowitz, Michael; Rayner, Christopher K; Ford, Alexander C; Reimann, Frank; Gribble, Fiona M","year":2026,"journal":"Gut, 75(2), 278-288","doi":"10.1136/gutjnl-2025-335393","pmid":"40701790","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Rectal bile acid exposure stimulates INSL5 secretion in humans, and circulating INSL5 levels are elevated and associated with diarrhea severity in bile acid diarrhea patients.","whyItMatters":"Identifying INSL5 as a mediator between bile acids and colonic motility could lead to new diagnostic markers and treatment targets for bile acid diarrhea.","specificNumbers":"","methodology":"Immunoassay-based measurement of INSL5 in serum/plasma samples from previously conducted studies of healthy volunteers and patients with chronic diarrhea.","limitations":"Used samples from previously conducted studies rather than a prospective design. The correlation between INSL5 and diarrhea severity does not prove causation."},{"rthcId":"RPEP-14838","title":"Inhaled Antibiotic and Biologic Formulations Targeting Pseudomonas aeruginosa.","authors":"Baral, Prodip Kumar; Dummer, Jack; Pletzer, Daniel; Das, Shyamal C","year":2026,"journal":"Pharmaceutics, 18(2)","doi":"10.3390/pharmaceutics18020162","pmid":"41754904","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Inhaled antibiotic and biologic formulations can achieve higher concentrations at the lung epithelial lining fluid, overcoming Pseudomonas resistance mechanisms including biofilm formation and efflux pumps.","whyItMatters":"Pseudomonas lung infections are a major cause of morbidity and mortality in chronic lung disease patients. Inhaled delivery could improve outcomes while reducing systemic side effects.","specificNumbers":"","methodology":"Narrative review of current research and development in inhaled antimicrobial formulations targeting Pseudomonas aeruginosa.","limitations":"Review article — does not present new experimental data. Many inhaled biologic formulations remain in early development stages."},{"rthcId":"RPEP-14839","title":"Efficacy and safety of European Medicines Agency (EMA)-approved pharmacological, endoscopic, and surgical treatments in different classes of obesity: A network meta-analysis of randomised controlled trials for the development of the SIO (Società Italiana Obesità) Italian guidelines for the diagnosis and treatment of overweight and obesity.","authors":"Barazzoni, Rocco; Monami, Matteo; Buscemi, Silvio; Busetto, Luca; De Luca, Maurizio; Navarra, Giuseppe; Ragghianti, Benedetta; Silverii, Giovanni Antonio; Belluzzi, Amanda; Mannucci, Edoardo; Sbraccia, Paolo","year":2026,"journal":"Diabetes, obesity & metabolism, 28(1), 358-378","doi":"10.1111/dom.70204","pmid":"41111360","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across all BMI classes, metabolic bariatric surgery produced the greatest weight loss, but newer obesity medications including tirzepatide significantly narrowed the efficacy gap compared to surgical interventions.","whyItMatters":"This is one of the first analyses to compare all approved obesity treatment categories head-to-head across BMI classes, helping clinicians match treatments to patient needs.","specificNumbers":"","methodology":"Systematic review and network meta-analysis of randomized controlled trials comparing obesity management medications, endoscopic bariatric procedures, and metabolic bariatric surgery vs lifestyle/placebo across BMI classes.","limitations":"Network meta-analysis relies on indirect comparisons across trials with different populations and follow-up periods. EMA-approved treatments may differ from those approved in other regions."},{"rthcId":"RPEP-14840","title":"Prior Exposure of Airway Epithelial Cells to Mycobacteria Reduces Subsequent Mycobacterium tuberculosis Infection and Resulting Inflammation.","authors":"Barclay, Amy M; Ninaber, Dennis K; Walburg, Kimberley V; Hiemstra, Pieter S; Ottenhoff, Tom H M; van der Does, Anne M; Joosten, Simone A","year":2026,"journal":"Journal of innate immunity, 18(1), 52-67","doi":"10.1159/000550118","pmid":"41474654","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Prior mycobacterial exposure of airway epithelial cells reduced intracellular infection efficiency of M. tuberculosis and M. avium during subsequent exposure and dampened cytokine responses.","whyItMatters":"Understanding how repeated mycobacterial exposures shape airway immunity could explain why some people resist TB infection and improve BCG vaccine strategies.","specificNumbers":"","methodology":"In vitro study using well-differentiated primary human bronchial epithelial cells (PBEC) exposed sequentially to Mtb, BCG, and M. avium, measuring infection rates and cytokine production.","limitations":"In vitro study using isolated cells — may not fully reflect the complex immune environment in living airways. Results may not translate directly to clinical outcomes."},{"rthcId":"RPEP-14841","title":"Approach to the Patient: Clinical Outcomes and Interim Strategies Following Discontinuation of Incretin Agonists.","authors":"Barenbaum, Sarah R; Aras, Mohini; Kashyap, Sangeeta; Aronne, Louis J","year":2026,"journal":"The Journal of clinical endocrinology and metabolism, 111(3), 870-878","doi":"10.1210/clinem/dgaf641","pmid":"41314250","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Discontinuation of incretin-based obesity medications results in weight regain and reversal of cardiometabolic improvements, with up to 50% of patients stopping treatment within 1-2 years.","whyItMatters":"With millions of patients starting GLP-1 medications, understanding discontinuation outcomes and having management plans for treatment gaps is critical for real-world obesity care.","specificNumbers":"","methodology":"Clinical review synthesizing evidence on outcomes following discontinuation of obesity pharmacotherapies, with practical interim management strategies.","limitations":"Review article — synthesizes existing evidence rather than generating new data. Discontinuation patterns may vary across healthcare systems and insurance coverage models."},{"rthcId":"RPEP-14842","title":"Incretin-based therapy and Parkinson's disease risk among patients with type 2 diabetes: Retrospective cohort study and meta-analysis.","authors":"Barer, Yael; Ast, Tal; Chodick, Gabriel; Twig, Gilad; Giladi, Nir","year":2026,"journal":"Parkinsonism & related disorders, 143, 108171","doi":"10.1016/j.parkreldis.2025.108171","pmid":"41468681","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Incretin-based therapy use in type 2 diabetes patients was associated with reduced Parkinson's disease incidence in both a retrospective cohort analysis and meta-analysis of available evidence.","whyItMatters":"If GLP-1 drugs can reduce Parkinson's risk, millions of diabetes patients may already be receiving neuroprotection, and these drugs could potentially be repurposed for Parkinson's prevention.","specificNumbers":"","methodology":"Retrospective cohort study of T2D patients (2008-2021) classified as IBT users vs non-users, supplemented by a meta-analysis of related studies.","limitations":"Retrospective observational design cannot prove causation. Healthy user bias may affect results — patients who take newer medications may be healthier overall."},{"rthcId":"RPEP-14843","title":"Risk of Sight-Threatening Diabetic Retinopathy with Glucagon-Like Peptide-1 Receptor Agonist Use in Routine Clinical Practice: Comparative Effectiveness of Semaglutide, Dulaglutide, Liraglutide, and Exenatide.","authors":"Barkmeier, Andrew J; Deng, Yihong; Swarna, Kavya Sindhu; Herrin, Jeph; Polley, Eric C; Umpierrez, Guillermo E; Galindo, Rodolfo J; Ross, Joseph S; Mickelson, Mindy M; McCoy, Rozalina G","year":2026,"journal":"Ophthalmology. Retina, 10(2), 142-151","doi":"10.1016/j.oret.2025.07.019","pmid":"40774571","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide, dulaglutide, liraglutide, and exenatide showed comparable risks of sight-threatening diabetic retinopathy complications in a large target trial emulation study.","whyItMatters":"Early semaglutide trial data raised concerns about diabetic eye disease risk. This real-world comparison across GLP-1 agents helps reassure clinicians and patients.","specificNumbers":"","methodology":"Retrospective observational study using target trial emulation framework with US commercial, Medicare Advantage, and Medicare fee-for-service claims data (2014-2022).","limitations":"Observational design using claims data — may miss unreported eye events. Target trial emulation reduces but does not eliminate confounding. No comparison to non-GLP-1 treatments."},{"rthcId":"RPEP-14844","title":"Sight Unseen: Glucagon-Like Peptide-1 (GLP-1) Agonism Therapy and Nonarteritic Anterior Ischemic Optic Neuropathy.","authors":"Barnett, Maxim J; Ibe, Festus; Lam, Justin","year":2026,"journal":"Cureus, 18(1), e100953","doi":"10.7759/cureus.100953","pmid":"41523719","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Type 2 diabetes patients on GLP-1 receptor agonists had a statistically significant 33.9% higher relative risk of NAION over five years (risk ratio 1.339, 95% CI 1.137-1.577, p=0.005), though the absolute risk difference was only 0.022%.","whyItMatters":"With millions of people now taking GLP-1 receptor agonists for diabetes and obesity, even rare adverse effects need to be understood so clinicians can monitor patients appropriately and counsel them about potential risks.","specificNumbers":"","methodology":"Retrospective cohort analysis using the TriNetX Global Collaborative Network with propensity-score matching across 20 covariates, yielding 388,333 patients per cohort.","limitations":"Retrospective design limits causal inference. The absolute risk increase is very small and may not be clinically meaningful. The exact mechanism linking GLP-1 therapy to NAION remains unknown. Confounders beyond the 20 matched covariates could contribute."},{"rthcId":"RPEP-14845","title":"Deep learning-enhanced 3D imaging unveils semaglutide impact on cardiac fibrosis.","authors":"Barrado-Ballestero, Sheyla; Yttergren, Sarah Torp; Hahn, Max; Rosenkilde, Marie Biviano; Jensen, Ditte Marie; Christensen, Michael; Thisted, Louise; Holmberg, Heidi Lindgreen; Teixeira, Geoffrey; Biering-Sørensen, Tor; Salinas, Casper Gravesen; Roostalu, Urmas","year":2026,"journal":"British journal of pharmacology, 183(5), 1030-1047","doi":"10.1111/bph.70217","pmid":"41121520","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A novel deep learning-based 3D whole-heart fibrosis quantification pipeline demonstrated that semaglutide significantly reduces myocardial fibrosis in a HFpEF preclinical model.","whyItMatters":"Better tools for measuring heart scarring could accelerate drug development for heart failure, and semaglutide's anti-fibrotic effects could benefit millions of HFpEF patients.","specificNumbers":"","methodology":"Development and validation of a deep learning-based whole-heart 3D imaging and fibrosis quantification pipeline, applied to evaluate semaglutide in a preclinical HFpEF model.","limitations":"Preclinical study — results need human validation. The deep learning model was trained on specific tissue types and may not generalize to all cardiac conditions."},{"rthcId":"RPEP-14846","title":"Real-world data of tirzepatide in obesity management: a multicenter study by the Italian Society of Obesity - Campania Region.","authors":"Barrea, Luigi; Verde, Ludovica; Galasso, Martina; Patrone, Renato; Digitale, Lucia; Limardi, Alessandro; Orio, Marcello; Ragozzino, Giovanni; Digitale, Luigi; Salvatore, Vittorio; Savoia, Antonella; Savastano, Silvia; Colao, Annamaria; Muscogiuri, Giovanna","year":2026,"journal":"EXCLI journal, 25, 191-203","doi":"10.17179/excli2025-9067","pmid":"41768862","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tirzepatide at 2.5 mg and 5.0 mg produced significant short-term weight loss and metabolic improvements in a real-world outpatient obesity population, confirming clinical trial benefits translate to routine practice.","whyItMatters":"Many patients remain on lower tirzepatide doses for extended periods. Confirming these doses work in real-world settings — not just controlled trials — is essential for clinical confidence.","specificNumbers":"","methodology":"Retrospective multicenter study across Italian Society of Obesity (SIO) Campania Region clinics evaluating short-term outcomes of tirzepatide 2.5 mg and 5.0 mg in adults with obesity.","limitations":"Retrospective design with short follow-up. Single-region study in Italy may not generalize to other populations. No control group for comparison."},{"rthcId":"RPEP-14847","title":"The dysregulation of innate immunity by Porphyromonas gingivalis in the etiology of Alzheimer's disease.","authors":"Barron, Annelise E; Lin, Jennifer S; Ryder, Mark I; Bergman, Peter","year":2026,"journal":"Journal of internal medicine, 299(3), 328-348","doi":"10.1111/joim.70060","pmid":"41424314","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"P. gingivalis infection may dysregulate and weaken innate immunity by degrading antimicrobial peptides (LL-37), Apolipoprotein E, interferons, and TNF-α, potentially enabling Alzheimer's disease pathology.","whyItMatters":"If gum disease bacteria truly contribute to Alzheimer's through immune disruption, oral health interventions could become a novel strategy for dementia prevention.","specificNumbers":"","methodology":"Perspective/hypothesis paper reviewing evidence linking P. gingivalis-mediated innate immune dysregulation to Alzheimer's disease etiology.","limitations":"Perspective paper presenting a hypothesis — not a clinical study. Causal relationship between P. gingivalis and Alzheimer's remains unproven in humans."},{"rthcId":"RPEP-14848","title":"Peptide drugs for obesity and type 2 diabetes mellitus: an overview of clinical trials.","authors":"Barzgar, Haniyeh; Darmadi, Darmadi; Nafisa, Jabbarova; Narkulov, Suxrob; Sviridova, Maria B","year":2026,"journal":"Clinica chimica acta; international journal of clinical chemistry, 581, 120772","doi":"10.1016/j.cca.2025.120772","pmid":"41354283","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Peptide-based metabolic regulators — particularly multi-receptor agonists targeting GLP-1, GIP, and glucagon receptors — have emerged as the most effective pharmacological class for obesity and T2DM treatment.","whyItMatters":"Understanding the full landscape of peptide drugs helps clinicians choose the best current options and anticipate even more effective treatments in the pipeline.","specificNumbers":"","methodology":"Comprehensive narrative review of clinical trials involving peptide therapeutics for obesity and type 2 diabetes, covering historical development through current and pipeline agents.","limitations":"Narrative review — not a systematic analysis. May not capture all ongoing trials. Focus on clinical efficacy may underweight safety and cost considerations."},{"rthcId":"RPEP-14849","title":"Renoprotective effect of dulaglutide in L-NAME-induced hypertensive nephropathy in rats: insight into the roles of PPAR-gamma and VEGF.","authors":"Bastawy, Nermeen; El-Mosallamy, Aliaa E M K; Rasheed, Rabab Ahmed; Sadek, A S; Khattab, R T; Ali, Esraa; Zaghloul, Randa A; Ghaly, Wael B A; Boushra, Amy F","year":2026,"journal":"Hypertension research : official journal of the Japanese Society of Hypertension, 49(3), 816-828","doi":"10.1038/s41440-025-02403-9","pmid":"41145714","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Dulaglutide (0.2 mg/kg/day) for six weeks ameliorated L-NAME-induced hypertensive kidney damage through PPAR-gamma activation and VEGF restoration, improving renal function and reducing inflammation.","whyItMatters":"Kidney protection is a critical unmet need in hypertension management. If GLP-1 drugs can directly protect kidneys, they could be valuable additions to treatment for hypertensive patients.","specificNumbers":"","methodology":"Animal study (rats) with L-NAME-induced hypertension treated with dulaglutide for 6 weeks, measuring renal function biomarkers, cytokines, redox status, and PPAR-gamma/VEGF expression.","limitations":"Animal study — rat models of hypertension may not fully translate to human hypertensive nephropathy. Single dose level tested."},{"rthcId":"RPEP-14850","title":"Exploratory Analysis of Circulating GLP-1, GIP, and TMAO in Relation to Coronary Artery Disease Severity in Patients with Exertional Angina.","authors":"Batirel, Saime; Cetinkaya, Bengu; Sahin, Ali; Alakbarova, Nodira; Guctekin, Tuba; Ozben, Beste; Tigen, Mustafa Kürşat","year":2026,"journal":"Biomedicines, 14(2)","doi":"10.3390/biomedicines14020260","pmid":"41751159","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Plasma GLP-1, GIP, and TMAO levels showed associations with coronary artery disease severity as measured by Gensini scores in patients undergoing angiography for exertional angina.","whyItMatters":"Understanding how gut hormones relate to heart disease severity could reveal new biomarkers for risk stratification and explain why GLP-1 drugs show cardiovascular benefits.","specificNumbers":"","methodology":"Cross-sectional study of 61 patients undergoing coronary angiography, stratified by Gensini score into normal, moderate-CAD, and severe-CAD groups, with measurement of plasma GLP-1, GIP, TMAO, and fatty acid composition.","limitations":"Small sample size (61 patients) limits statistical power. Cross-sectional design cannot establish causation. Single-center study may not generalize broadly."},{"rthcId":"RPEP-14851","title":"Weekly Subcutaneous VK2735, a GIP/GLP-1 Receptor Dual Agonist, for Weight Management: Phase 2, Randomized, 13-Week VENTURE Study.","authors":"Bays, Harold E; Toth, Phillip; Alkhouri, Naim; Pullman, John; Freilich, Bradley; Neutel, Joel; Ji, Summer; Stubbe, Scott; Hedges, Parke; Lian, Brian","year":2026,"journal":"Obesity (Silver Spring, Md.), 34(3), 537-549","doi":"10.1002/oby.70106","pmid":"41508550","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Weekly subcutaneous VK2735 produced significant dose-dependent weight reduction over 13 weeks, with active treatment groups showing meaningful weight loss compared to placebo.","whyItMatters":"More GIP/GLP-1 dual agonist options could increase competition, lower costs, and provide alternatives for patients who don't respond well to existing medications.","specificNumbers":"","methodology":"Phase 2, randomized, double-blind, placebo-controlled, dose-ranging study (VENTURE) of weekly subcutaneous VK2735 in adults with obesity/overweight and ≥1 comorbidity, conducted August 2023–February 2024.","limitations":"Short 13-week duration — long-term efficacy and safety unknown. Excluded diabetes patients, limiting applicability. Phase 2 sample sizes are relatively small."},{"rthcId":"RPEP-14852","title":"Predicting ICU admission in geriatric hip fracture patients with heart failure: the role of O-POSSUM and heart failure subtypes.","authors":"Bayındır, Serpil; Kazez, Muhammed; Yalın, Mustafa","year":2026,"journal":"BMC geriatrics, 26(1)","doi":"10.1186/s12877-026-07085-7","pmid":"41618186","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"O-POSSUM scores and BNP levels showed predictive value for ICU admission in geriatric hip fracture patients with heart failure, with ICU admission rates differing across HFpEF, HFmrEF, and HFrEF subtypes.","whyItMatters":"Better prediction of ICU needs allows hospitals to allocate resources effectively and prepare families for post-surgical care in high-risk elderly patients.","specificNumbers":"","methodology":"Retrospective cohort study of 97 geriatric heart failure patients undergoing hip fracture surgery (2022-2024), comparing O-POSSUM, BNP, and CCI for ICU admission prediction.","limitations":"Small sample size (97 patients) split across three heart failure subtypes. Retrospective single-center design limits generalizability."},{"rthcId":"RPEP-14853","title":"Optimizing delivery of an anti-cytomegalovirus inhibitory peptide using a cell-penetrating peptide.","authors":"Beeton, Komal; Haskell, Jacob P; Mitra, Dipanwita; Taylor, Erin B; Bidwell, Gene L","year":2026,"journal":"The Journal of general virology, 107(1)","doi":"10.1099/jgv.0.002210","pmid":"41528341","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Adding the cell-penetrating peptide SynB1 to the ELP-P10 anti-CMV peptide construct enhanced intracellular delivery and antiviral potency at lower concentrations.","whyItMatters":"CMV infection remains a major threat for transplant recipients and newborns, and current treatments have serious toxicity. More effective peptide delivery could enable safer antiviral therapy.","specificNumbers":"","methodology":"In vitro study testing SynB1-ELP-P10 fusion construct for cell penetration efficiency and anti-CMV activity compared to ELP-P10 alone.","limitations":"In vitro study only — in vivo pharmacokinetics and safety of the triple-fusion construct need to be evaluated. CMV specificity of the enhanced construct requires further characterization."},{"rthcId":"RPEP-14854","title":"The multifaceted role of antimicrobial peptides in neurodegeneration: Insights from Drosophila and beyond.","authors":"Behera, Priyatama; Rangappa, Nagaraj; Chandrashekar, Madhura; Mishra, Amit; Chinnathambi, Subashchandrabose; Mishra, Monalisa","year":2026,"journal":"Advances in protein chemistry and structural biology, 149, 419-444","doi":"10.1016/bs.apcsb.2025.08.003","pmid":"41581940","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Antimicrobial peptides are dysregulated in glial and neuronal tissues across multiple neurodegenerative diseases, contributing to neuroinflammation, mitochondrial dysfunction, and neuronal loss through Toll and IMD immune pathway overactivation.","whyItMatters":"Understanding how immune peptides contribute to brain disease could reveal new therapeutic targets for neurodegenerative conditions that currently have no cure.","specificNumbers":"","methodology":"Narrative review of AMP roles in neurodegeneration, with emphasis on Drosophila models of Huntington's, Alzheimer's, Parkinson's, ALS, and Ataxia-telangiectasia.","limitations":"Heavy reliance on Drosophila models — insect immune systems differ from human systems. Review does not present new experimental data."},{"rthcId":"RPEP-14855","title":"Effect of GLP-1 Receptor Agonists in Heart Failure with Preserved Ejection Fraction: A Systematic Review and Meta-Analysis.","authors":"Behers, Benjamin J; Sanchez, Christian; Hozayen, Omar; Hozayen, Yousef; Kammer, Rheiner; Corrigan, William T; Stephenson-Moe, Christoph A; Miller, Matthew W; Idriss, Mohab; Cekan, Luis E; King, Alan D; Brown, Garrett H; Hamad, Karen M","year":2026,"journal":"Journal of cardiovascular development and disease, 13(2)","doi":"10.3390/jcdd13020103","pmid":"41745350","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RAs showed no significant effect on cardiovascular mortality or worsening heart failure events in HFpEF patients but were associated with improved quality of life and favorable safety data across 6 RCTs with 5,564 participants.","whyItMatters":"HFpEF has very few effective treatments. Even quality-of-life improvements are clinically meaningful for these patients who often have significant symptom burden.","specificNumbers":"","methodology":"Systematic review and meta-analysis of 6 randomized controlled trials investigating GLP-1 RAs in HFpEF patients, with primary outcomes of cardiovascular mortality and worsening HF events.","limitations":"Meta-analysis of heterogeneous trials with different GLP-1 agents and follow-up durations. May be underpowered for mortality outcomes. Quality-of-life measures varied across trials."},{"rthcId":"RPEP-14856","title":"GLP-1 is not enough: can glucagon fill the energy expenditure gap?","authors":"Beji, Sarra; Caron, Alexandre","year":2026,"journal":"Neuroendocrinology, 1-26","doi":"10.1159/000550812","pmid":"41678436","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Glucagon receptor agonism increases lipid oxidation, substrate mobilization, and energy expenditure, complementing GLP-1R appetite suppression and potentially overcoming adaptive metabolic decline during weight loss.","whyItMatters":"The metabolic slowdown during weight loss is a major reason people plateau or regain weight. Adding glucagon receptor activation could be the key to sustaining weight loss long-term.","specificNumbers":"","methodology":"Narrative review integrating historical, preclinical, and clinical evidence on glucagon as a regulator of energy expenditure and its therapeutic potential alongside GLP-1 agonism.","limitations":"Review article — no new experimental data. Glucagon's hyperglycemic effects pose safety challenges that need to be balanced against metabolic benefits."},{"rthcId":"RPEP-14857","title":"Lung Metastases from Meningioma Diagnosed on Whole Body 68Ga-DOTATOC PET/CT and Successfully Targeted With 177Lu-DOTATATE.","authors":"Bekkhoucha, Adam; Agrigoroaie, Laurentiu; Deandreis, Desiree; Guyon, David; Chehade, Feras","year":2026,"journal":"Clinical nuclear medicine, 51(4), 335-337","doi":"10.1097/RLU.0000000000006352","pmid":"41771035","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Refractory meningioma with lung metastases showed high somatostatin receptor expression on 68Ga-DOTATOC PET/CT, enabling successful targeted treatment with 177Lu-DOTATATE peptide receptor radionuclide therapy.","whyItMatters":"Demonstrates that peptide-based theranostics (combined diagnosis and therapy) can manage rare metastatic meningiomas that fail conventional treatments.","specificNumbers":"","methodology":"Single case report of a meningioma patient with lung metastases diagnosed by 68Ga-DOTATOC PET/CT and treated with 177Lu-DOTATATE PRRT.","limitations":"Single case report — cannot be generalized. Not all meningiomas express somatostatin receptors at levels sufficient for PRRT."},{"rthcId":"RPEP-14858","title":"Challenges in the management of idiopathic intracranial hypertension.","authors":"Belanger, Katherine; Ashraf, Omar; Rau, Jill; Hui, Ferdinand; Fargen, Kyle M","year":2026,"journal":"Journal of neurointerventional surgery","doi":"10.1136/jnis-2025-024599","pmid":"41558864","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Weight loss remains the only disease-modifying therapy for IIH, with GLP-1 RAs offering a promising pharmacologic approach, though all current treatments are limited by side effects, poor long-term efficacy, or restricted applicability.","whyItMatters":"IIH is becoming more common as obesity rates rise. Understanding treatment gaps highlights where new therapies like GLP-1 drugs could make the biggest difference.","specificNumbers":"","methodology":"Narrative review of current challenges in IIH management, covering lifestyle interventions, pharmacotherapy (including GLP-1 RAs), and surgical options.","limitations":"Review article — no new data. GLP-1 RA evidence for IIH is still early and largely extrapolated from their weight loss effects."},{"rthcId":"RPEP-14859","title":"Comparative efficacy of GLP-1 RA, tirzepatide and SGLT-2 inhibitors in metabolic liver disease: A network meta-analysis.","authors":"Belančić, Andrej; Antza, Christina; Poutachidis, Anastasios; Palaska, Smaro; Gkrinia, Elvira Meni Maria; Faour, Andrea Katrin; Sener, Yusuf Ziya; Sener, Seher; Sultana, Rehena","year":2026,"journal":"British journal of clinical pharmacology","doi":"10.1002/bcp.70492","pmid":"41703425","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Network meta-analysis provides comparative efficacy rankings of GLP-1 RAs, tirzepatide, and SGLT-2 inhibitors for NAFLD/NASH treatment, enabling indirect comparisons across drug classes.","whyItMatters":"No drug is currently FDA-approved specifically for NAFLD/NASH. Understanding which existing metabolic drugs best improve liver outcomes could guide off-label use and future trial design.","specificNumbers":"","methodology":"Systematic literature review and network meta-analysis of controlled trials from MEDLINE, EMBASE, and Cochrane databases, reported per PRISMA guidelines.","limitations":"Network meta-analysis relies on indirect comparisons. Included trials may use different liver endpoints and follow-up durations. Not all trials were designed primarily for liver outcomes."},{"rthcId":"RPEP-14860","title":"Molecular diversity and antimicrobial properties of extracts from different organs of Tunisian extremophilic plants.","authors":"Ben Brahim, Raoua; Voisin, Sébastien N; Fouzai, Khaoula; Bulet, Philippe; Regaya, Imed","year":2026,"journal":"Journal of proteomics, 327, 105622","doi":"10.1016/j.jprot.2026.105622","pmid":"41679502","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"MALDI mass spectrometry and proteomics revealed substantial molecular diversity in antimicrobial extracts from 4 Tunisian extremophilic plant species, with activity varying by plant organ.","whyItMatters":"As antibiotic resistance grows, plants adapted to harsh environments offer a largely unexplored reservoir of novel antimicrobial molecules.","specificNumbers":"","methodology":"Characterization of plant extracts from roots, leaves, and seeds of 4 extremophilic Tunisian plants using MALDI mass spectrometry and off-gel bottom-up proteomics, with antimicrobial activity testing.","limitations":"Early-stage discovery — specific antimicrobial peptides not fully purified or characterized. In vitro testing only. Yield and scalability not assessed."},{"rthcId":"RPEP-14861","title":"Cardiac Biomarkers, Echocardiography, and Outpatient Cardiac Monitoring for Evaluation of Emergency Department Patients With Syncope: A Systematic Review and Analysis of Direct Evidence for SAEM GRACE.","authors":"Benabbas, Roshanak; Zehtabchi, Shahriar; Wakai, Abel; Allen, Robert; deSouza, Ian S; Richards, Rebekah J; Curley, David; Dunne, Eric; Sinert, Richard","year":2026,"journal":"Academic emergency medicine : official journal of the Society for Academic Emergency Medicine, 33(2), e70175","doi":"10.1111/acem.70175","pmid":"41201260","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Evidence supporting the routine use of troponin, BNP, echocardiography, and outpatient cardiac monitoring in ER syncope patients is limited, with unclear benefit for 30-day outcomes.","whyItMatters":"Millions of ER visits for fainting result in expensive cardiac testing. Evidence-based guidance on which tests are actually useful could reduce unnecessary costs and patient anxiety.","specificNumbers":"","methodology":"Systematic review of diagnostic accuracy studies evaluating cardiac biomarkers, echocardiography, and outpatient monitoring in adult ED patients with syncope, following SAEM GRACE methodology.","limitations":"Systematic review quality depends on available primary studies, which were often small or retrospective. Different syncope etiologies may respond differently to testing."},{"rthcId":"RPEP-14862","title":"O-Acetyl-Serine Supplementation Enhances Insulin Secretion and Improves Postprandial Glycaemia in Lean and Prediabetic Mice.","authors":"Benatar, Clara; Zhang, Xufei; Haddam, Ines; Ribes, Sandy; Bobet, Sophie; Monnoye, Magali; Lamy, Elodie; Grassin-Delyle, Stanislas; Juillard, Vincent; Layec, Séverine; Delorme, Christine; Douard, Véronique","year":2026,"journal":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 40(4), e71543","doi":"10.1096/fj.202502925R","pmid":"41718459","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"OAS acts as a glucose-dependent insulin secretagogue, accumulating in the pancreas after oral administration and dose-dependently improving postprandial glycemia in lean and prediabetic mice.","whyItMatters":"A natural, glucose-dependent insulin secretagogue from gut microbes could offer a safer approach to prediabetes intervention than existing drugs, with lower hypoglycemia risk.","specificNumbers":"","methodology":"Preclinical study developing a targeted OAS quantification method and testing oral OAS supplementation in lean and prediabetic mouse models, measuring plasma/tissue levels, insulin secretion, and glycemic outcomes.","limitations":"Mouse study only — human metabolism and response may differ significantly. Long-term safety and efficacy not assessed. OAS bioavailability in humans unknown."},{"rthcId":"RPEP-14863","title":"Effects of neoadjuvant glucagon-like-peptide 1 receptor agonists on weight loss after bariatric surgery.","authors":"Benavidez, Maria Charina; Redpath, Sophia; Trautmann, Stephanie; Ceron, Santiago; Schimpke, Scott; Myers, Jonathan; Omotosho, Philip; Torquati, Alfonso; Skertich, Nicholas J","year":2026,"journal":"Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery, 22(1), 18-23","doi":"10.1016/j.soard.2025.09.010","pmid":"41162242","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Neoadjuvant GLP-1RA use (8.5% of patients) did not significantly affect post-surgical weight loss outcomes after sleeve gastrectomy or Roux-en-Y gastric bypass.","whyItMatters":"Surgeons and patients can be reassured that taking GLP-1 drugs before surgery does not compromise bariatric surgical weight loss outcomes.","specificNumbers":"","methodology":"Retrospective cohort study of 422 bariatric surgery patients (36 with pre-op GLP-1RA, 386 without) from July 2022 to June 2023, using t-tests and multivariable analysis.","limitations":"Small GLP-1RA group (n=36) limits statistical power. Retrospective single-center design. Short follow-up period. Cannot account for all confounding variables."},{"rthcId":"RPEP-14864","title":"Unlocking the potential of EphA2 with precision-guided cancer therapy: bicycle drug conjugates.","authors":"Bennett, Gavin; Riedl, Jitka; Mudd, Gemma","year":2026,"journal":"Journal of translational medicine, 24(1)","doi":"10.1186/s12967-026-07870-3","pmid":"41782030","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Bicycle drug conjugates represent a novel peptide-based approach to targeting EphA2 in solid tumors, potentially overcoming the efficacy and safety limitations of previous EphA2-targeting agents.","whyItMatters":"Pancreatic and head-and-neck cancers have very poor survival rates. New precision therapies targeting EphA2 could provide treatment options where few currently exist.","specificNumbers":"","methodology":"Review of EphA2 as a cancer target, previous therapeutic failures, and the emerging bicycle drug conjugate platform as a next-generation approach.","limitations":"Review article — BDCs targeting EphA2 are still in development. Clinical efficacy and safety data are limited or pending."},{"rthcId":"RPEP-14865","title":"Gb-piscidin: A novel antimicrobial and immunostimulant peptide from gilthead seabream (Sparus aurata) - Identification, tissue-specific expression, recombinant production, and biological evaluation.","authors":"Berenjkar, Najmeh; Kalbassi, Mohammad Reza; Hosseinkhani, Saman; Beemelmanns, Christine; Moghaddam, Jamshid Amiri","year":2026,"journal":"Fish & shellfish immunology, 169, 111049","doi":"10.1016/j.fsi.2025.111049","pmid":"41319890","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Gb-piscidin, a novel 22-residue class 1 piscidin from gilthead seabream, exhibits broad antimicrobial activity and immunostimulatory potential, with a Cys9-Cys16 disulfide bridge critical for function.","whyItMatters":"Aquaculture faces major disease challenges, and natural antimicrobial peptides from fish themselves could provide sustainable alternatives to antibiotics in fish farming.","specificNumbers":"","methodology":"Gene identification, tissue-specific expression analysis, recombinant production in E. coli, structural characterization, and biological evaluation of antimicrobial and immunomodulatory activity.","limitations":"Single species study — applicability to other fish species or human use not established. Recombinant production in E. coli may differ from native peptide properties."},{"rthcId":"RPEP-14866","title":"Cell-Penetrating Peptides and Supercharged Proteins: A Comprehensive Protocol from Isolation to Cellular Uptake.","authors":"Beribisky, Alexander V; Sarne, Victoria; Huber, Anna; Hengstschläger, Markus; Laccone, Franco; Steinkellner, Hannes","year":2026,"journal":"Molecular pharmaceutics, 23(3), 1845-1857","doi":"10.1021/acs.molpharmaceut.5c01560","pmid":"41709632","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A comprehensive and replicable protocol for isolation, biochemical characterization, and quantitative cellular uptake analysis of CPP-fusion proteins and supercharged proteins was developed and validated.","whyItMatters":"Standardized protocols accelerate the field of intracellular drug delivery by enabling researchers to reliably produce and test cell-penetrating peptide systems.","specificNumbers":"","methodology":"Methods development paper providing protocols for protein isolation, characterization, and quantitative cellular uptake analysis using MeCP2 CPP-fusion constructs as a model system.","limitations":"Protocol validated with MeCP2 constructs — may need optimization for other protein cargoes. In vitro cellular uptake may not predict in vivo delivery efficiency."},{"rthcId":"RPEP-14867","title":"Who Wins the Battle Against Obesity? A Network Meta-Analysis Comparing Tirzepatide and Semaglutide.","authors":"Bernardi, Julia C; Cavalcante, Deivyd V S; Huntermann, Ramon; Molinari, Maria E; Zanon, Luana Z; Khater, Jacinthe; Gomez, Victor A; Fischer-Bacca, Caroline O","year":2026,"journal":"Journal of diabetes, 18(2), e70192","doi":"10.1111/1753-0407.70192","pmid":"41664890","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Network meta-analysis of RCTs indicates tirzepatide (dual GIP/GLP-1 agonist) provides greater body weight reduction and glycemic improvement compared to semaglutide (GLP-1 agonist alone) in obesity.","whyItMatters":"This directly addresses the most common clinical question in obesity pharmacotherapy: which of the two leading drugs should I prescribe?","specificNumbers":"","methodology":"Network meta-analysis using a frequentist approach, comparing RCTs of tirzepatide or semaglutide versus placebo or active comparators for obesity treatment.","limitations":"Network meta-analysis relies on indirect comparisons across different trials. Patient populations, dosing, and follow-up may not be directly comparable. Few head-to-head RCTs exist."},{"rthcId":"RPEP-14868","title":"LEAP2 modulates β-adrenergic triggered cardiac responses and provokes antihypertensive effects.","authors":"Berrio, Sixta Isabel Atencio; Carvalho, Jhulle Horrane; Dutra, João Batista; Eliezeck, Marcos; Scalzo, Sergio; Ribeiro, Juliana Vila Verde; Mendonça, Michelle Mendanha; Gomes, Rodrigo Mello; Pedrino, Gustavo Rodrigues; Colombari, Eduardo; Castrogiovanni, Daniel; Milagros, Sisti Maria; Racioppi, Maria Florencia; Petroff, Martin Vila; Cantel, Sonia; Fehrentz, Jean-Alain; Guatimosim, Silvia; Perelló, Mario; de Castro, Carlos Henrique; Xavier, Carlos Henrique","year":2026,"journal":"Life sciences, 390, 124243","doi":"10.1016/j.lfs.2026.124243","pmid":"41619965","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"LEAP2 reduces blood pressure in both normal and hypertensive rats and modulates β-adrenergic cardiac responses, acting through GHSR antagonism and inverse agonism.","whyItMatters":"Discovering that an antimicrobial peptide directly regulates blood pressure opens new avenues for hypertension treatment and reveals unexpected connections between metabolism and cardiovascular function.","specificNumbers":"","methodology":"Multi-level study: in vivo (Wistar and spontaneously hypertensive rats), ex vivo (isolated hearts), and in vitro (cardiomyocytes) assessment of LEAP2 cardiovascular effects.","limitations":"Animal study — effects in humans unknown. Acute IV administration may not reflect chronic therapeutic use. Complex interaction between GHSR constitutive activity and LEAP2 needs further characterization."},{"rthcId":"RPEP-14869","title":"An analog of Clarias gariepinus Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP-38) contributes to immune homeostasis and defences against Vibrio parahaemolyticus in Litopenaeus vannamei.","authors":"Betancourt, Jesús Luis; Ihedimbu, Ijeoma; Rodríguez-Ramos, Tania; Coronado-Molina, Daniel Eduardo; Carpio, Yamila; Estrada, Mario Pablo; Hernández-López, Jorge; Ramos, Laida; Dixon, Brian","year":2026,"journal":"Fish & shellfish immunology, 169, 111047","doi":"10.1016/j.fsi.2025.111047","pmid":"41317752","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A Clarias gariepinus PACAP-38 analog enhanced immune homeostasis and defense against V. parahaemolyticus in L. vannamei shrimp, demonstrating cross-species antimicrobial peptide applications.","whyItMatters":"Shrimp aquaculture loses billions annually to Vibrio infections. Natural peptide-based immune boosters could replace antibiotics and reduce resistance development.","specificNumbers":"","methodology":"In vivo study testing PACAP-38 analog administration in Pacific white shrimp, measuring immune parameters and survival following Vibrio parahaemolyticus challenge.","limitations":"Aquaculture study — applicability to commercial-scale farming not assessed. Long-term effects and optimal dosing regimens need further study."},{"rthcId":"RPEP-14870","title":"GLP-1 physiology and pharmacology along the gut-brain axis.","authors":"Beutler, Lisa R","year":2026,"journal":"The Journal of clinical investigation, 136(2)","doi":"10.1172/JCI194744","pmid":"41542773","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 receptor agonists achieve transformative obesity treatment through dual peripheral (metabolic, GI) and central (appetite, reward) mechanisms along the gut-brain axis.","whyItMatters":"Understanding how GLP-1 drugs work at a mechanistic level helps optimize their use and explains why they are more effective than any previous obesity medication.","specificNumbers":"","methodology":"Comprehensive review of GLP-1 physiology, pharmacology, and therapeutic mechanisms along the gut-brain axis.","limitations":"Review article — does not present new data. Focus on GLP-1 may underweight contributions of other hormonal systems to obesity."},{"rthcId":"RPEP-14871","title":"Cardiac Magnetic Resonance Findings and Their Association with Clinical Outcomes in Pediatric Pulmonary Arterial Hypertension: An Exploratory Study.","authors":"Beyazal, Meryem; Keceli, Merter; Dogan, Oguzhan; Ece, Ibrahim","year":2026,"journal":"Journal of clinical medicine, 15(3)","doi":"10.3390/jcm15031107","pmid":"41682787","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CMR-derived right ventricular parameters (RVEF, RVESVi, RVMi, VMI) and septal curvature were associated with clinical outcomes in 36 children with pulmonary arterial hypertension.","whyItMatters":"Children with PAH need careful monitoring, but invasive cardiac catheterization has risks. MRI offers a non-invasive alternative to track disease progression and treatment response.","specificNumbers":"","methodology":"Prospective exploratory study of 36 children with PAH evaluated using cardiac magnetic resonance, measuring ventricular volumetric and functional parameters and correlating with clinical outcomes.","limitations":"Small sample (36 patients). Exploratory study design — findings need validation in larger cohorts. Pediatric MRI requires sedation in younger children, limiting accessibility."},{"rthcId":"RPEP-14872","title":"Liver gains beyond glycemic control: GLP-1 vs. SGLT2 in metabolic dysfunction-associated steatohepatitis (MASH): A real-world data analysis.","authors":"Beyene, Elizabeth; Chirumamilla, Lakshmi; Bisrat, Mekdem; Bowen, Allan; Fetle, Yonas; Wilkerson, Brandon; Wudeneh, Addishiwot; Gillani, Syed Fahad; Larbi, Daniel; Michael, Miriam","year":2026,"journal":"Clinics and research in hepatology and gastroenterology, 50(2), 102760","doi":"10.1016/j.clinre.2026.102760","pmid":"41500355","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Real-world comparison of GLP-1 RAs versus SGLT-2 inhibitors in MASH patients evaluated cirrhosis incidence, hepatocellular carcinoma rates, and liver enzyme profile changes.","whyItMatters":"MASH affects millions and has limited treatment options. Knowing which common diabetes drug better protects the liver could change prescribing practices immediately.","specificNumbers":"","methodology":"Retrospective cohort study using de-identified electronic health records from the TriNetX network, comparing MASH patients on GLP-1 RAs versus SGLT-2 inhibitors.","limitations":"Retrospective observational design — cannot prove causation. EHR data may have coding inconsistencies. Confounding by indication likely (patients may receive different drugs for different reasons)."},{"rthcId":"RPEP-14873","title":"Marine-Inspired Antimicrobial Peptides Disrupt Gene Expression at the DNA Level.","authors":"Beyer, Luisa I; Thoma, Johannes; Acha Alarcon, Leonarda; Unksov, Ivan N; Karlsson, Roger; Inda-Díaz, Juan S; Tietze, Alesia A","year":2026,"journal":"ACS infectious diseases, 12(1), 447-459","doi":"10.1021/acsinfecdis.5c01000","pmid":"41363146","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Marine-derived peptides L3 and L3-K cause extensive proteome remodeling (175 and 120 differentially expressed proteins) and disrupt gene expression at the DNA level rather than acting through membrane lysis.","whyItMatters":"Understanding that these peptides work at the DNA level — not just the membrane — opens new strategies for antibiotic development that bacteria may find harder to resist.","specificNumbers":"","methodology":"TMT-based quantitative proteomics of uropathogenic E. coli treated with peptides L3 and L3-K, investigating mode of action through protein expression changes and nucleoid effects.","limitations":"In vitro study in a single bacterial species (uropathogenic E. coli). DNA-level effects need further characterization. Proteomic changes don't prove direct DNA binding."},{"rthcId":"RPEP-14874","title":"Computational insights into terpene-induced modulation of amyloid-β peptide (Aβ1-42) aggregation-favoring conformations.","authors":"Bezerra, Iverson Conrado; Viana, Jéssika de Oliveira; Bisneto, Jocelin Santa Rita; Cavalcante, Gabriel Gomes; Barbosa de Luna, João Gabriel; da Silva, Artur José; Weber, Karen Cacilda; Machado, Giovanna; de Lima Filho, José Luiz; Gubert, Priscila","year":2026,"journal":"Journal of molecular graphics & modelling, 143, 109268","doi":"10.1016/j.jmgm.2025.109268","pmid":"41478158","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Molecular dynamics simulations show caryophyllene and copaene bind to Aβ1-42 and disrupt aggregation-prone conformations in the C-terminal and central hydrophobic domains.","whyItMatters":"If natural terpenes can prevent amyloid aggregation, they could become accessible, low-cost supplements for Alzheimer's prevention — but lab and clinical validation are essential.","specificNumbers":"","methodology":"Computational study using molecular docking, molecular dynamics simulations, and MM/PBSA free energy calculations to assess terpene-Aβ1-42 interactions.","limitations":"Computational study only — no wet lab or animal validation. Simulated binding may not reflect actual biological activity. Blood-brain barrier penetration not assessed."},{"rthcId":"RPEP-14875","title":"Antimicrobial peptides isolated from probiotics as an alternative to antibiotics against Salmonella infection.","authors":"Bhandari, Menuka; Lokesh, Dhanashree; Thenissery, Anusree; Shrestha, Rajeev; Rajashekara, Gireesh","year":2026,"journal":"Applied and environmental microbiology, 92(2), e0165425","doi":"10.1128/aem.01654-25","pmid":"41615215","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Antimicrobial peptides isolated from probiotic bacteria demonstrate activity against Salmonella, representing a viable alternative to conventional antibiotics for poultry food safety.","whyItMatters":"Non-typhoidal Salmonella is the top cause of foodborne illness deaths in the US. Probiotic-derived antimicrobials could improve food safety while reducing antibiotic resistance.","specificNumbers":"","methodology":"Isolation and characterization of antimicrobial peptides from probiotic bacteria, with evaluation of anti-Salmonella activity.","limitations":"Early-stage research — scalability for commercial poultry use not assessed. In vivo efficacy in poultry production not validated."},{"rthcId":"RPEP-14876","title":"A generalizable assay for intracellular accumulation to profile cytosolic drug delivery in mammalian cells.","authors":"Bhandari, Sobika; Ongwae, George M; Dash, Rachita; Liu, Zichen; Chordia, Mahendra D; He, Yuchen; Pires, Marcos M","year":2026,"journal":"Communications chemistry, 9(1), 94","doi":"10.1038/s42004-026-01898-8","pmid":"41652100","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The CHAMP assay (Chloroalkane HaloTag Azide-based Membrane Penetration) accurately reports cytosolic accumulation in high throughput, distinguishing true cytosolic delivery from membrane association or endosomal trapping.","whyItMatters":"Most biologics and peptide drugs fail because they can't reach intracellular targets. An accurate cytosolic delivery assay could dramatically improve drug development success rates.","specificNumbers":"","methodology":"Development and validation of the CHAMP assay for measuring cytosolic drug delivery using a minimally disruptive azide tag in mammalian cells.","limitations":"Assay requires azide-tagged compounds — tag may alter some molecules' behavior. Validated in mammalian cell lines; tissue-specific penetration may differ."},{"rthcId":"RPEP-14877","title":"Designing highly tunable laminin-inspired bioactive peptide hydrogel-based biomaterials for directing cellular response.","authors":"Bhandary, Ranit; Sen, Sourav; Mohanty, Sweta; Roy, Sangita","year":2026,"journal":"Journal of materials chemistry. B, 14(4), 1325-1341","doi":"10.1039/d5tb01989c","pmid":"41502329","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Laminin-derived bioactive peptide hydrogels with tunable self-assembly properties can direct cellular responses through engineered biochemical cues mimicking the ECM.","whyItMatters":"Better biomaterials that mimic the body's natural environment are essential for growing tissues in the lab and developing regenerative therapies.","specificNumbers":"","methodology":"Design and characterization of laminin-inspired peptide hydrogels using non-conventional self-assembly approaches, with evaluation of cellular response and tunability.","limitations":"In vitro characterization — in vivo performance and degradation behavior not assessed. Translation to clinical tissue engineering applications requires further development."},{"rthcId":"RPEP-14878","title":"Antimicrobial proteins regulating neuroinflammation.","authors":"Bhusal, Anup; Lee, Won-Ha; Suk, Kyoungho","year":2026,"journal":"Annals of medicine, 58(1), 2610072","doi":"10.1080/07853890.2025.2610072","pmid":"41487016","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"AMPs are expressed in the CNS at basal levels, upregulated in neurological disorders, and play multifunctional roles in neuroinflammation including immune modulation and neuroprotection beyond antimicrobial activity.","whyItMatters":"Understanding the dual role of AMPs in infection defense and brain inflammation could reveal new targets for treating neurodegenerative and neuroinflammatory diseases.","specificNumbers":"","methodology":"Review of antimicrobial peptide/protein expression, regulation, and functions in the central nervous system and neurological disorders.","limitations":"Review article — synthesizes existing evidence without new experimental data. The complexity of AMP roles in the CNS makes therapeutic targeting challenging."},{"rthcId":"RPEP-14879","title":"A novel antimicrobial peptide FxCy2 against Helicobacter pylori: Isolation and purification from Lactobacillus paracasei FX-6.","authors":"Bi, Bo; Kang, Meng; Lin, Qianru; Wang, Qun; Li, Xiaoqing; Ye, Zhuming; Ho, Chi-Tang; Cao, Yong","year":2026,"journal":"Food research international (Ottawa, Ont.), 225, 118069","doi":"10.1016/j.foodres.2025.118069","pmid":"41508490","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"FxCy2, a novel AMP from Lactobacillus paracasei FX-6, inhibited H. pylori (MIC = 1.25 mg/mL) and demonstrated synergistic antibacterial effects with clinical antibiotics.","whyItMatters":"H. pylori infects half the world's population and antibiotic resistance is rising. A probiotic-derived peptide that enhances existing antibiotics could improve treatment outcomes.","specificNumbers":"","methodology":"Isolation and purification of FxCy2 from Lactobacillus paracasei FX-6 fermentation supernatant, with MIC determination and synergy testing with clinical antibiotics against H. pylori.","limitations":"In vitro study — in vivo efficacy in the acidic stomach environment not tested. MIC of 1.25 mg/mL is relatively high. Stability and delivery need optimization."},{"rthcId":"RPEP-14880","title":"GFOGER-Modified PLGA/HA Electrospun Scaffolds Facilitate BMSCs' Osteogenic Differentiation.","authors":"Bi, Ming; Liu, Xiaoli; Zhang, Chunyu; Wang, Xiaoyun; Li, Jiahui; Dong, Yuanjun; Mao, Jifu; Hu, Xingyou; Han, Hui; Wang, Yongliang","year":2026,"journal":"ACS applied bio materials, 9(4), 2340-2346","doi":"10.1021/acsabm.5c02528","pmid":"41636710","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GFOGER peptide functionalization of PLGA/HA electrospun scaffolds enhanced BMSC adhesion and osteogenic commitment through integrin α2β1-mediated signaling.","whyItMatters":"Better bone scaffolds could improve outcomes for patients with fractures, bone defects, and orthopedic surgeries by accelerating natural bone healing.","specificNumbers":"","methodology":"Fabrication of GFOGER-modified PLGA/HA electrospun scaffolds with evaluation of BMSC attachment, osteogenic differentiation, and integrin-mediated signaling.","limitations":"In vitro study — in vivo bone regeneration performance not yet tested. Long-term scaffold degradation and peptide stability need evaluation."},{"rthcId":"RPEP-14881","title":"Use of semaglutide after acute coronary syndrome: an exploratory retrospective study.","authors":"Biasin, Marco; Stratinaki, Maria; Cordioli, Nicolò; Armani, Ilaria; De Giovanni, Sara; Aletras, George; Betta, Davide; Callegarin, Luca; Gambaro, Alessia; Morani, Giovanni","year":2026,"journal":"Journal of cardiovascular medicine (Hagerstown, Md.), 27(2), 144-150","doi":"10.2459/JCM.0000000000001837","pmid":"41703411","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide prescribed at hospital discharge after acute coronary syndrome in T2DM patients was feasible in real-world practice, providing exploratory data on early post-ACS GLP-1 RA initiation.","whyItMatters":"Starting cardiovascular-protective medications early after a heart attack could maximize benefit during the highest-risk period for recurrent events.","specificNumbers":"","methodology":"Retrospective, multicenter observational study of adults with T2DM hospitalized for ACS who were prescribed semaglutide at discharge.","limitations":"Retrospective observational design. Exploratory study — no control group or randomization. Small study with limited follow-up likely."},{"rthcId":"RPEP-14882","title":"Efficacy and Safety of Glucagon-Like Peptide-1 Receptor Agonists Following Bariatric Surgery: A Systematic Review and Meta-Analysis.","authors":"Bilal, Abdur Rafay; Ibrahim, Muhammad; Arfin, S M Washaqul; Bilal, Abdur Raheem; Balach, Rahul; Qureshi, Shaheer; Gaba, Hateem; Collins, Peter; Ahmed, Raheel; Waqas, Saad Ahmed","year":2026,"journal":"Endocrinology, diabetes & metabolism, 9(2), e70102","doi":"10.1002/edm2.70102","pmid":"41721616","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RAs post-bariatric surgery promoted additional weight loss and improved metabolic markers including BMI, cholesterol, triglycerides, fasting glucose, blood pressure, and HbA1c compared to placebo.","whyItMatters":"Weight recurrence after bariatric surgery affects 20-30% of patients. GLP-1 drugs could provide a pharmacological rescue strategy for surgical patients who aren't achieving optimal outcomes.","specificNumbers":"","methodology":"Systematic review and meta-analysis of RCTs from PubMed, Cochrane CENTRAL, and Scopus through March 2025, comparing GLP-1 RA to placebo in post-bariatric surgery patients.","limitations":"Limited number of RCTs available. Heterogeneity in surgical procedures, GLP-1 agents, timing of drug initiation, and follow-up periods."},{"rthcId":"RPEP-14883","title":"Comparative Evaluation of Antimicrobial Peptide and Chlorin e6 Immobilization Strategies on GelMA Hydrogels for Enhanced Antibiofilm Activity via Photodynamic Therapy.","authors":"Bilgiç, Eda; Çelebi, Nisa Nilsu; Avşar, Nermin Topaloğlu; Karaman, Didem Şen; Pulat, Günnur","year":2026,"journal":"Journal of biomedical materials research. Part B, Applied biomaterials, 114(1), e70026","doi":"10.1002/jbmb.70026","pmid":"41486216","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GelMA hydrogels combining antimicrobial peptide TetraF2W-RR with photosensitizer Chlorin e6 showed enhanced antibiofilm activity via photodynamic therapy, with immobilization strategy affecting efficacy.","whyItMatters":"Chronic wounds affect millions worldwide and are increasingly complicated by antibiotic-resistant biofilms. Combination approaches using peptides and light therapy could overcome current treatment failures.","specificNumbers":"","methodology":"Comparative evaluation of different immobilization strategies for AMP and Chlorin e6 on GelMA hydrogels, assessing antibiofilm activity through photodynamic therapy approaches.","limitations":"In vitro biofilm testing — in vivo wound healing performance not evaluated. Light penetration depth limits applicability to surface wounds."},{"rthcId":"RPEP-14884","title":"Dual-functional β-TCP based injectable bone grafts functionalized with peptides for enhanced osteogenesis and broad-spectrum biofilm inhibition.","authors":"Bilgiç, Eda; Özkaya, Şevval; Gençer, Duygu; Karaman, Ozan; Pulat, Günnur","year":2026,"journal":"Biomaterials advances, 183, 214739","doi":"10.1016/j.bioadv.2026.214739","pmid":"41619601","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A dual-functional β-TCP injectable bone graft functionalized with osteogenic and antimicrobial peptides enhanced bone formation while providing broad-spectrum biofilm inhibition.","whyItMatters":"Infected bone defects are a major clinical challenge with high failure rates. A single material that both grows bone and fights infection could dramatically improve surgical outcomes.","specificNumbers":"","methodology":"Development and characterization of peptide-functionalized β-TCP putty-form injectable bone grafts, evaluating mechanical properties, osteogenic potential, and antimicrobial activity.","limitations":"In vitro and early preclinical testing — long-term in vivo performance, degradation, and peptide release kinetics need evaluation."},{"rthcId":"RPEP-14885","title":"Impact of GLP-1 analogues on immune-mediated inflammatory diseases: A systematic review.","authors":"Birda, Chhagan L; Ibrahim, Fadwa; Chatterjee, Abhirup; Jena, Anuraag; Sharma, Vishal; Sebastian, Shaji","year":2026,"journal":"Autoimmunity reviews, 25(1), 103936","doi":"10.1016/j.autrev.2025.103936","pmid":"41077375","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RAs demonstrated anti-inflammatory effects in patients with immune-mediated inflammatory disorders, though significant heterogeneity prevented meta-analysis.","whyItMatters":"Millions of people have autoimmune inflammatory diseases with limited treatment options. If GLP-1 drugs can double as anti-inflammatory agents, they could benefit patients with both metabolic and immune conditions.","specificNumbers":"","methodology":"Systematic review of PubMed, Scopus, and Embase (searched April 2025) for studies reporting GLP-1 RA use in patients with IMIDs.","limitations":"Significant heterogeneity prevented meta-analysis. Most evidence comes from observational studies or secondary analyses of metabolic trials."},{"rthcId":"RPEP-14886","title":"Regular collagen peptide administration exerts anti-obesity effects in high-caloric diet-fed rodents-a systematic review with meta-analysis of animal trials.","authors":"Bischof, Kevin; Moitzi, Anna Maria; König, Daniel","year":2026,"journal":"International journal of obesity (2005), 50(1), 8-22","doi":"10.1038/s41366-025-01905-3","pmid":"41168365","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Meta-analysis of rodent studies confirms collagen peptide administration consistently alleviates obesity and related symptoms in high-caloric diet-fed animals.","whyItMatters":"If collagen peptides can help combat obesity, they represent an accessible, affordable, and well-tolerated supplement that could complement other weight management strategies.","specificNumbers":"","methodology":"Systematic review and meta-analysis conducted per PRISMA guidelines, pooling animal trials of collagen peptide supplementation during high-fat/high-caloric diets.","limitations":"Animal studies only — human translation uncertain. High heterogeneity in collagen peptide sources, doses, and experimental protocols. Publication bias possible."},{"rthcId":"RPEP-14887","title":"Tirzepatide counteracts brown adipose tissue whitening, inflammation, and mitochondrial dysfunction in estrogen-deficient obese diabetic mice.","authors":"Bittencourt, Julie Oliveira A; Marcondes-de-Castro, Ilitch A; Marinho, Thatiany Souza; Aguila, Marcia Barbosa; Mandarim-de-Lacerda, Carlos Alberto","year":2026,"journal":"Life sciences, 386, 124155","doi":"10.1016/j.lfs.2025.124155","pmid":"41412277","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tirzepatide (10 nmol/kg/day for 4 weeks) reversed brown adipose tissue whitening, reduced inflammation, and restored mitochondrial function in ovariectomized obese diabetic mice.","whyItMatters":"Postmenopausal women are at high metabolic risk. Showing tirzepatide works specifically in this context supports its use in this underserved patient population.","specificNumbers":"","methodology":"Preclinical study with 4 groups of mice (control, ovariectomized, obese-diabetic, obese-diabetic-ovariectomized) treated with tirzepatide for 4 weeks after 12-week disease induction.","limitations":"Mouse model — human translation needs confirmation. Ovariectomy is an acute model of estrogen loss, different from gradual menopause."},{"rthcId":"RPEP-14888","title":"Delayed-Onset Amiodarone Induced Thyrotoxicosis After Glucagon-Like Peptide-1 Agonist-Related Weight Loss.","authors":"Black, Meghan L; Coyle, Catherine G; Bernet, Victor J; McLeod, Christopher J; Chindris, Ana-Maria","year":2026,"journal":"JCEM case reports, 4(2), luaf313","doi":"10.1210/jcemcr/luaf313","pmid":"41531741","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 agonist-induced weight loss likely mobilized adipose-stored amiodarone, causing delayed-onset amiodarone-induced thyrotoxicosis 14 months after drug discontinuation.","whyItMatters":"As millions of people take GLP-1 weight loss drugs, clinicians must recognize that rapid fat loss can release fat-stored medications and toxins, causing unexpected adverse effects.","specificNumbers":"","methodology":"Single case report of delayed amiodarone-induced thyrotoxicosis temporally associated with GLP-1 RA-related weight loss.","limitations":"Single case report — causation not definitively proven. Other factors may have contributed to the thyrotoxicosis."},{"rthcId":"RPEP-14889","title":"A Human Mass Balance and Metabolism Study of [14C]-Ubrogepant in Healthy Male Adults.","authors":"Boinpally, Ramesh R; Rowe, Joshua; Chandrasekar, Pushpa; White, Rebecca B; Marcantonio, Eugene E; Trainor, Nicole; Liang, Yuexia; Maciolek, Cheri; Small, James H; Houle, Robert; Hafey, Michael J; Xie, Huizhi; Yabut, Jocelyn; Fandozzi, Christine","year":2026,"journal":"Clinical pharmacology in drug development, 15(1), e70010","doi":"10.1002/cpdd.70010","pmid":"41562504","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Mean total radioactivity recovery was 92.4% after a single 50 mg oral dose of [14C]-ubrogepant, with the drug undergoing extensive hepatic metabolism.","whyItMatters":"Understanding how migraine drugs are metabolized helps predict drug interactions, guide dosing in liver or kidney disease, and optimize treatment safety.","specificNumbers":"","methodology":"Mass balance and metabolism study using [14C]-labeled ubrogepant (50 mg, ~200 µCi) in 6 healthy male adults, tracking radioactivity recovery and metabolite identification.","limitations":"Small sample (6 males only). Single-dose study — may not reflect steady-state metabolism. Healthy volunteers may not represent migraine patient population."},{"rthcId":"RPEP-14890","title":"Effect of semaglutide with metformin for weight loss and fertility in polycystic ovary syndrome (PCOS) patients with obesity: A pilot prospective study.","authors":"Bolek, Tomáš; Turňová, Petra; Janošova, Svetlana; Péč, Martin Jozef; Ságová, Ivana; Nagy, Norbert; Jurica, Jakub; Mokáň, Marián; Samoš, Matej","year":2026,"journal":"Clinical nutrition ESPEN, 71, 102885","doi":"10.1016/j.clnesp.2025.102885","pmid":"41421448","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Subcutaneous semaglutide combined with metformin produced significant weight loss and improved fertility outcomes in 20 consecutive PCOS patients with obesity and prediabetes.","whyItMatters":"PCOS affects 10% of women of reproductive age, and obesity worsens fertility outcomes. A treatment that addresses both weight and fertility simultaneously fills a critical gap.","specificNumbers":"","methodology":"Pilot prospective study of 20 consecutive PCOS patients with obesity and prediabetes treated with semaglutide plus metformin, evaluating weight loss and fertility outcomes.","limitations":"Small pilot study (n=20) without a control group. Prospective but not randomized or blinded. Short follow-up for fertility outcomes."},{"rthcId":"RPEP-14891","title":"Phage Display-Derived Peptides Have Neutralizing Activities Against Biofilm Formation by Candida albicans, Candidozyma auris and Candida parapsilosis.","authors":"Bolotnikov, Grigory; Gruber, Daniel; Walter, Jan-Christoph; Kühnel, Kim; Kemal, Turgay; Rodriguez, Armando; Preising, Nico; Ständker, Ludger; Firacative, Carolina; Spellerberg, Barbara; Stenger, Steffen; Rosenau, Frank; Kissmann, Ann-Kathrin","year":2026,"journal":"Pharmaceuticals (Basel, Switzerland), 19(2)","doi":"10.3390/ph19020286","pmid":"41754826","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Phage display-derived neutralizing AMPs (nAMPs) effectively inhibited biofilm formation by C. albicans, C. auris, and C. parapsilosis through modulation of pathogenic behavior rather than cell killing.","whyItMatters":"Candida auris is a CDC urgent threat. Anti-biofilm peptides that work without killing could provide treatment options that don't drive further antifungal resistance.","specificNumbers":"","methodology":"Phage display screening for peptides with anti-biofilm activity against three Candida species, evaluating neutralizing (non-killing) antimicrobial mechanisms.","limitations":"In vitro biofilm assays — in vivo efficacy not tested. Non-killing approaches may need to be combined with immune support for clinical effectiveness."},{"rthcId":"RPEP-14892","title":"Incretin Analogues for Weight Reduction in Non-Diabetic Obese: A Review of Liraglutide, Semaglutide, and Tirzepatide Beyond Glycemic Control.","authors":"Bonga, Krishna Nikhila; Padhan, Milan","year":2026,"journal":"Rambam Maimonides medical journal, 17(1)","doi":"10.5041/RMMJ.10565","pmid":"41605830","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Liraglutide, semaglutide, and tirzepatide all demonstrate significant efficacy for weight reduction in non-diabetic obesity, with additional cardiometabolic benefits beyond glycemic control.","whyItMatters":"Non-diabetic obesity is the most common use case for these drugs. Understanding their comparative benefits helps guide the best choice for each patient.","specificNumbers":"","methodology":"Narrative review of clinical evidence for incretin analogues (liraglutide, semaglutide, tirzepatide) in non-diabetic obese patients.","limitations":"Narrative review — not a systematic analysis. Limited head-to-head comparison data between the three drugs."},{"rthcId":"RPEP-14893","title":"GLP-1 Receptor Agonists Are Associated With Reduced Mortality Following Diabetic Foot Ulcers: A Nationwide Observational Study.","authors":"Bonnet, Jean-Baptiste; Huguet, Helena; Avignon, Antoine; Duflos, Claire; Sultan, Ariane","year":2026,"journal":"Diabetes care","doi":"10.2337/dc25-2120","pmid":"41615296","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RA use was associated with reduced 1-year mortality following first diabetic foot ulcer in a nationwide French cohort, with secondary analysis also examining mortality after major lower-limb amputation.","whyItMatters":"Diabetic foot ulcer patients have a 5-year mortality rate approaching 50%. Any treatment that reduces mortality in this population could save thousands of lives annually.","specificNumbers":"","methodology":"Retrospective nationwide cohort study using the French SNDS health data system, identifying adults with incident diabetic foot ulcers and analyzing associated factors for 1-year mortality.","limitations":"Observational design — cannot prove GLP-1 drugs caused the survival benefit. Healthy user bias possible. French healthcare system may not generalize globally."},{"rthcId":"RPEP-14894","title":"Poplar CLE peptides promoting ectomycorrhizal symbiosis identified through genome-wide analysis of responsive small secreted peptides.","authors":"Bonnot, Clémence; Morin, Emmanuelle; Da Silva Machado, Emilie; Veneault-Fourrey, Claire; Kohler, Annegret; Martin, Francis","year":2026,"journal":"Plant physiology, 200(3)","doi":"10.1093/plphys/kiag071","pmid":"41731702","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Genome-wide analysis identified poplar CLE peptides that promote ectomycorrhizal symbiosis, revealing plant small secreted peptide roles in tree-fungus association.","whyItMatters":"Understanding how trees communicate with beneficial fungi could improve forestry, ecosystem restoration, and carbon sequestration efforts.","specificNumbers":"","methodology":"Genome-wide identification and characterization of responsive small secreted peptides in poplar, with functional analysis of CLE peptides in ectomycorrhizal symbiosis.","limitations":"Poplar-specific study — peptide functions may differ in other tree species. Lab conditions may not fully reflect field-level symbiotic dynamics."},{"rthcId":"RPEP-14895","title":"Prevalence and Associations of Systemic Inflammation in Heart Failure Across the Spectrum of Ejection Fraction.","authors":"Borlaug, Barry A; Holse, Cecilie; Jung, Mette Holme; Lincoff, A Michael; Mulvagh, Sharon L; Stærk-Østergaard, Jacob; Tuttle, Katherine R; Petrie, Mark C","year":2026,"journal":"JACC. Heart failure, 14(2), 102712","doi":"10.1016/j.jchf.2025.102712","pmid":"41099689","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Systemic inflammation in HFpEF is linked to cardiovascular-kidney-metabolic conditions, while HFrEF inflammation develops secondary to cardiac stress, with distinct patterns across the ejection fraction spectrum.","whyItMatters":"Understanding that different heart failure types have different inflammatory drivers could lead to tailored anti-inflammatory therapies rather than one-size-fits-all approaches.","specificNumbers":"","methodology":"Analysis of inflammation prevalence and associations across heart failure subtypes (HFpEF, HFmrEF, HFrEF) examining cardiovascular-kidney-metabolic connections.","limitations":"Observational analysis — inflammation markers are associative, not necessarily causal. Cross-sectional data may miss temporal dynamics of inflammation."},{"rthcId":"RPEP-14896","title":"GIPR signaling modulates PYY-induced hypophagia and malaise in rodents.","authors":"Borner, Tito; Pataro, Allison M; Curtis, Genevieve R; Alonso, Brandon; Hu, Jiayin; Fortin, Samantha M; Koul-Tiwari, Richa; Hughes, Emily; Kong, Jimmy X; Jordan, Emily; Barnes, Robert; Bernardo, Barbara; Gardner, Maxwell; Ma, Wenzhe; Gosset, James R; Esquejo, Ryan M; Fortin, Jean-Philippe; De Jonghe, Bart C; Bence, Kendra K; Hayes, Matthew R","year":2026,"journal":"Molecular metabolism, 106, 102334","doi":"10.1016/j.molmet.2026.102334","pmid":"41679433","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GIP receptor signaling modulates PYY-induced appetite suppression and reduces associated nausea and malaise in rodents, suggesting a mechanism for improved tolerability in multi-agonist obesity drugs.","whyItMatters":"Nausea causes up to half of GLP-1 drug discontinuations. Understanding how GIP reduces nausea could lead to better-tolerated weight loss medications.","specificNumbers":"","methodology":"Preclinical rodent studies investigating the interaction between GIPR signaling and PYY-induced hypophagia and malaise, examining emetic neurocircuitry modulation.","limitations":"Rodent study — nausea is difficult to measure precisely in animals. Human nausea mechanisms may differ. PYY-based therapies are not yet clinically available."},{"rthcId":"RPEP-14897","title":"Plant- and Microalgae-Based Biotechnological Strategies for Affordable and Non-Invasive Delivery of Antidiabetic Peptides.","authors":"Boscart, Thibault; Barras, Alexandre; Plaisance, Valérie; Pawlowski, Valérie; Giovanelli, Emerson; Bardor, Muriel; D'Hulst, Christophe; Abderrahmani, Amar","year":2026,"journal":"Pharmaceutics, 18(2)","doi":"10.3390/pharmaceutics18020223","pmid":"41754966","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Plant- and microalgae-based biotechnological platforms offer affordable production and non-invasive (oral) delivery strategies for antidiabetic peptides including insulin and GLP-1 RAs.","whyItMatters":"Diabetes drug costs are a global crisis. Making insulin and GLP-1 drugs in plants could reduce costs by orders of magnitude and eliminate injection barriers.","specificNumbers":"","methodology":"Review of biotechnological strategies for producing antidiabetic peptides in plant and microalgae systems, evaluating cost reduction and oral delivery potential.","limitations":"Review of emerging technology — most plant-produced peptides are still in development. Regulatory hurdles, dosing consistency, and stability remain significant challenges."},{"rthcId":"RPEP-14898","title":"A cystine-containing cationic lipopeptide-based injectable hydrogel with antimicrobial activities against multi-drug resistant strains and anti-biofilm efficacy against methicillin-resistant Staphylococcus aureus.","authors":"Bose, Supratim; Poddar, Neha; Sharma, Swrajit Nath; Deb, Swapnendu; Mondal, Tanushree; Banerjee, Arindam","year":2026,"journal":"Journal of materials chemistry. B, 14(2), 749-760","doi":"10.1039/d5tb01110h","pmid":"41416965","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A cystine-containing cationic lipopeptide injectable hydrogel demonstrated broad antimicrobial activity against MDR strains and effective anti-biofilm activity against MRSA.","whyItMatters":"MRSA biofilm infections on medical devices and in wounds are life-threatening and nearly untreatable. An injectable antimicrobial hydrogel could revolutionize hospital infection management.","specificNumbers":"","methodology":"Design and evaluation of a lipopeptide-based injectable hydrogel for antimicrobial activity against MDR pathogens and MRSA biofilm disruption.","limitations":"In vitro testing — in vivo efficacy, toxicity, and degradation behavior need evaluation. Regulatory pathway for injectable antimicrobial hydrogels is complex."},{"rthcId":"RPEP-14899","title":"Role of the trigeminal system in pancreatic innervation: new concept and challenge - a narrative review.","authors":"Bou Malhab, Fady M; Jabbour, Serge A; Defronzo, Ralph; Nemr, Rita","year":2026,"journal":"Endocrine research, 1-10","doi":"10.1080/07435800.2026.2631091","pmid":"41701512","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The trigeminal system may contribute to pancreatic innervation via CGRP and substance P neuropeptides, potentially influencing pancreatic blood flow, inflammation, and endocrine function.","whyItMatters":"Understanding all neural inputs to the pancreas could reveal new therapeutic targets for diabetes, pancreatitis, and pancreatic cancer pain.","specificNumbers":"","methodology":"Narrative review exploring the hypothesis that trigeminal sensory neuropeptides participate in pancreatic innervation and function.","limitations":"Hypothesis-based review — the trigeminal-pancreatic connection is proposed but not definitively proven. Direct experimental evidence is limited."},{"rthcId":"RPEP-14900","title":"Artificial Intelligence as a Catalyst for Antimicrobial Discovery: From Predictive Models to De Novo Design.","authors":"Boudza, Romaisaa; Bounou, Salim; Segura-Garcia, Jaume; Moukadiri, Ismail; Maicas, Sergi","year":2026,"journal":"Microorganisms, 14(2)","doi":"10.3390/microorganisms14020394","pmid":"41753681","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"AI approaches including predictive models and de novo generative design are accelerating antimicrobial and antimicrobial peptide discovery, offering a transformative response to the global resistance crisis.","whyItMatters":"Antimicrobial resistance kills over 1 million people annually. AI-driven discovery could provide new antibiotics faster and cheaper than traditional methods.","specificNumbers":"","methodology":"Comprehensive review of AI applications in antimicrobial discovery, covering predictive models, machine learning screening, and de novo peptide design.","limitations":"Review article — many AI-designed antimicrobials are still in early validation. Computational predictions don't always translate to in vivo efficacy."},{"rthcId":"RPEP-14901","title":"Motion as a Language: Transformer-Based Classification of Antimicrobial Peptide Conformational Dynamics.","authors":"Bouvier, Benjamin","year":2026,"journal":"Journal of chemical theory and computation, 22(3), 1215-1223","doi":"10.1021/acs.jctc.5c01690","pmid":"41609302","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Transformer-based models successfully classified antimicrobial peptides using conformational dynamics as input features, treating molecular motion sequences as a language for machine learning.","whyItMatters":"Current AMP screening relies on static sequence data. Analyzing dynamics could identify active peptides that static methods miss, improving drug discovery hit rates.","specificNumbers":"","methodology":"Application of transformer neural networks to AMP conformational dynamics data from molecular simulations, developing motion-based classification of antimicrobial activity.","limitations":"Computational study — classification accuracy needs validation against experimental antimicrobial data. Molecular dynamics simulations are computationally expensive."},{"rthcId":"RPEP-14902","title":"Glucagon-like peptide-1 receptor agonist versus sodium-glucose cotransporter-2 inhibitor persistence in Medicare Advantage beneficiaries with type 2 diabetes, cardiovascular risk, and obesity.","authors":"Bowe, Andy; Hayes, Mary; John, Isha; Diaz, Monica; Dixon, Suzanne; Poonawalla, Insiya","year":2026,"journal":"Diabetes, obesity & metabolism, 28(1), 472-484","doi":"10.1111/dom.70219","pmid":"41165079","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RA initiators showed higher treatment persistence compared to SGLT2i initiators among Medicare Advantage beneficiaries with T2DM, including subgroups with cardiovascular disease and obesity.","whyItMatters":"Medication persistence directly affects outcomes. Understanding which drugs patients stay on longer helps clinicians make better prescribing decisions and payers design coverage.","specificNumbers":"","methodology":"Retrospective claims analysis using Humana Healthcare Research data comparing treatment persistence and augmentation between new GLP-1 RA and SGLT2i users with type 2 diabetes.","limitations":"Claims data cannot capture reasons for discontinuation. Medicare Advantage population may not represent all diabetes patients. Persistence does not equal adherence."},{"rthcId":"RPEP-14903","title":"Psychometric Validation of the Simplicity of Diabetes Treatment Questionnaire (Sim-Q) for Type 2 Diabetes.","authors":"Boye, Kristina S; Cutts, Katelyn N; Coyne, Karin S; Matza, Louis S","year":2026,"journal":"Advances in therapy","doi":"10.1007/s12325-025-03448-5","pmid":"41678136","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The Sim-Q questionnaire demonstrated valid psychometric properties for measuring perceived treatment simplicity in type 2 diabetes patients across 8 US clinical sites.","whyItMatters":"Treatment simplicity affects adherence and outcomes. A validated tool to measure it enables better comparison of treatment regimens and patient-centered care.","specificNumbers":"","methodology":"Psychometric validation study of the Sim-Q across 8 US clinical sites, evaluating reliability, validity, and responsiveness in T2D patients on various treatment regimens.","limitations":"US-only validation — may need cultural adaptation for other countries. Patient perception of simplicity is subjective and may be influenced by prior treatment experience."},{"rthcId":"RPEP-14904","title":"Recurrent gastrointestinal bleeding after Peptide Receptor Radionuclide Therapy for a small intestine neuroendocrine tumor.","authors":"Brackenier, C; Leupe, H; Dekervel, J; Verslype, C; De Hertogh, G; Topal, H; Rasschaert, G; Deroose, C M; Van Herpe, F","year":2026,"journal":"Acta gastro-enterologica Belgica, 89(1), 83-86","doi":"10.51821/89.1.14522","pmid":"41745641","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Three cycles of 177Lu-DOTATATE PRRT for small intestine neuroendocrine tumor led to recurrent GI bleeding requiring four ICU admissions, 14 packed cell transfusions, and eventual surgery.","whyItMatters":"As PRRT becomes more widely used for neuroendocrine tumors, recognizing this serious GI bleeding complication is critical for patient safety and monitoring.","specificNumbers":"","methodology":"Single case report of severe GI bleeding complication following PRRT with 177Lu-DOTATATE for small intestine neuroendocrine tumor.","limitations":"Single case report — incidence of this complication is unknown. Individual patient factors may have contributed to the severity."},{"rthcId":"RPEP-14905","title":"\"GLP-1 Agonists vs. Bariatric Surgery: A Global Health Network Analysis of Panniculectomy Outcomes\".","authors":"Braud, Savannah C; Terry, Peyton; Azoury, Said","year":2026,"journal":"Plastic and reconstructive surgery","doi":"10.1097/PRS.0000000000012955","pmid":"41729134","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Panniculectomy outcomes and perioperative lab values were compared between patients with prior GLP-1 RA use and those with prior bariatric surgery using the TriNetX global network.","whyItMatters":"As the route to weight loss shifts from surgery to medications, plastic surgeons need data on how these different weight loss methods affect subsequent body contouring outcomes.","specificNumbers":"","methodology":"Retrospective global health network analysis using TriNetX comparing panniculectomy outcomes in GLP-1 RA users versus post-bariatric surgery patients.","limitations":"Retrospective database analysis — cannot control for all confounders. GLP-1 and bariatric patients may differ in weight loss magnitude and speed."},{"rthcId":"RPEP-14906","title":"Semaglutide mitigates the loss of fat-free mass and decreased energy expenditure observed after diet restriction. Insights from an obese minipig model.","authors":"Bredum, Simon Krogh; Jacobsen, Julie M; Halling, Jens Frey; Blom, Ida; Lewis, Christopher T A; Ochala, Julien; Fredholm, Merete; Lundh, Sofia; Schmücker, Malte; Ozenne, Brice; Domingos, Ana I; Hald, Bjørn Olav; Larsen, Steen; Cirera, Susanna; Christoffersen, Berit Oestergaard","year":2026,"journal":"American journal of physiology. Endocrinology and metabolism","doi":"10.1152/ajpendo.00480.2024","pmid":"41671030","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide treatment preserved fat-free mass and energy expenditure compared to diet restriction alone in obese minipigs, demonstrating more favorable body composition changes.","whyItMatters":"Critics worry GLP-1 drugs cause excessive muscle loss. This data suggests semaglutide actually preserves muscle better than equivalent calorie restriction, addressing a key safety concern.","specificNumbers":"","methodology":"Controlled study in diet-induced obese Göttingen minipigs (n=8/group): control (ad libitum), semaglutide-treated, and diet-restricted groups, measuring body composition and energy expenditure.","limitations":"Minipig model — not human data. Small group sizes (n=8). Short study duration may not capture long-term body composition changes."},{"rthcId":"RPEP-14907","title":"Retatrutide Shows Multiple Metabolic Benefits in Diet-Induced Obese MASH Mouse and Hamster Models.","authors":"Briand, François; Le Cudennec, Camille; Grasset, Estelle; Breyner, Natalia; Bigot, Claire; Dillard, Pierre; Sulpice, Thierry","year":2026,"journal":"Obesity (Silver Spring, Md.)","doi":"10.1002/oby.70155","pmid":"41741376","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Retatrutide reduced body weight by 31% and showed multiple metabolic benefits including reduced fat mass, food intake, and liver disease markers in obese MASH mouse and hamster models.","whyItMatters":"Retatrutide targets all three receptors (vs two for tirzepatide), potentially offering even greater weight loss and metabolic benefits for the most severe obesity cases.","specificNumbers":"","methodology":"Preclinical evaluation of retatrutide in diet-induced obese MASH mouse and hamster models, measuring body weight, composition, food/water intake, and metabolic parameters.","limitations":"Animal models — human efficacy and safety may differ. Both fat and lean mass reduction occurred, raising muscle preservation questions."},{"rthcId":"RPEP-14908","title":"Calcium-binding protein expression alone is insufficient to identify and classify GABAergic neurons in macaque cortex.","authors":"Brigande, Alev M; Krueger, Juliane; Park, Connor; Disney, Anita A","year":2026,"journal":"bioRxiv : the preprint server for biology","doi":"10.64898/2026.01.26.701495","pmid":"41659629","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Calcium-binding protein expression (PV, CB, CR) alone cannot reliably identify and classify GABAergic neuron subclasses in macaque cortex due to extensive co-expression patterns.","whyItMatters":"Many brain research studies rely on calcium-binding protein markers to identify neuron types. If these markers are unreliable, decades of neuronal classification may need revision.","specificNumbers":"","methodology":"Immunohistochemical analysis of PV, CB, and CR expression patterns in GABAergic neurons of macaque neocortex.","limitations":"Macaque cortex study — patterns may differ in other primate species or brain regions. Single-method (immunohistochemistry) approach."},{"rthcId":"RPEP-14909","title":"Bariatric surgery vs. GLP-1 receptor agonists among primarily medicare and medicaid patients with diabetes: a 3-year analysis.","authors":"Brown, Avery; Patel, Suhani S; Li, Elizabeth; Vu, Alexander Hien; Somoza, Eduardo; Chen, Jialin; Zhang, Donglan; Massie, Allan B; Orandi, Babak J; Segev, Dorry; Parikh, Manish; Chhabra, Karan","year":2026,"journal":"Surgical endoscopy, 40(1), 671-678","doi":"10.1007/s00464-025-12403-y","pmid":"41326727","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Three-year comparison of bariatric surgery versus GLP-1 RAs in Medicare and Medicaid patients with diabetes provides real-world effectiveness data in a publicly insured population.","whyItMatters":"Medicare and Medicaid patients face unique access barriers and disease burdens. Understanding treatment effectiveness in this population guides coverage decisions and equity.","specificNumbers":"","methodology":"Retrospective 3-year analysis of Medicare and Medicaid claims data comparing outcomes between bariatric surgery and GLP-1 RA treatment in patients with diabetes.","limitations":"Retrospective claims analysis — cannot account for all confounders. Selection bias between surgery and medication patients is significant."},{"rthcId":"RPEP-14910","title":"Design Differences and Usability Risks in GLP-1 Pen Injectors: A Comparative Study of a Generic and Reference Device.","authors":"Brunet-Manquat, Laurie; Combedazou, Anne; Ramus, Claire; Frolet, Cécile","year":2026,"journal":"PDA journal of pharmaceutical science and technology","doi":"10.5731/pdajpst.2025-000043.1","pmid":"41698692","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Comparative evaluation identified design differences and usability risks between a proposed generic GLP-1 pen injector and the reference listed drug device that could affect safe substitution.","whyItMatters":"Millions of patients may switch between GLP-1 pen devices as generics enter the market. Design differences that cause dosing errors could have serious consequences.","specificNumbers":"","methodology":"Preliminary comparative usability study of a generic vs reference GLP-1 pen injector device for ANDA submission evaluation.","limitations":"Preliminary study — full-scale human factors validation needed. May not capture all real-world use errors."},{"rthcId":"RPEP-14911","title":"NLRP3 inhibition by VTX3232 tempers inflammation resulting in reduced body weight, hyperglycemia, and hepatic steatosis in obese male mice.","authors":"Bultinck, Jennyfer; Yuan, Shendong; Cantuti-Castelvetri, Ludovico; Brosens, Lander; Bracke, Debby; Collins, James; Goethals, Jens; Christianson, Christina; Nuss, John; Ogilvie, Kathleen","year":2026,"journal":"Molecular metabolism, 103, 102282","doi":"10.1016/j.molmet.2025.102282","pmid":"41242536","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"VTX3232 NLRP3 inhibition reduced body weight, hyperglycemia, and hepatic steatosis in obese male mice by tempering metabolic inflammation.","whyItMatters":"If inflammation-targeting drugs can independently reduce metabolic disease markers, they could be combined with GLP-1 drugs for even greater benefit.","specificNumbers":"","methodology":"Preclinical study testing VTX3232, a novel NLRP3 inflammasome inhibitor, in obese male mice, measuring body weight, glucose levels, and liver steatosis.","limitations":"Mouse study — human efficacy and safety unknown. Male mice only — sex differences in metabolic inflammation may exist."},{"rthcId":"RPEP-14912","title":"Pneumococcal S protein coordinates cell wall modification and repair to resist host antimicrobials.","authors":"Burnier, Jessica; Gallay, Clement; Bruce, Kevin E; Bjånes, Elisabet; Martin, Louise; Jim, Kin Ki; Tsui, Ho-Ching Tiffany; Cremers, Amelieke J H; Mignolet, Johann; Vollmer, Daniela; Biboy, Jacob; Nizet, Victor; Vollmer, Waldemar; Winkler, Malcolm E; Veening, Jan-Willem","year":2026,"journal":"Nature microbiology, 11(1), 282-300","doi":"10.1038/s41564-025-02184-4","pmid":"41420059","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"S protein coordinates cell wall modification and repair in Streptococcus to resist host-derived antimicrobial peptides, revealing a key bacterial defense mechanism against innate immunity.","whyItMatters":"Group A Streptococcus causes over 500,000 deaths annually. Understanding how it resists our immune defenses could enable new therapeutic strategies.","specificNumbers":"","methodology":"Multi-method study using genetic, biochemical, single-molecule, in vitro and in vivo analyses to characterize S protein function in antimicrobial resistance.","limitations":"Primarily streptococcal study — mechanism may differ in other bacterial species. Drug targeting of S protein has not yet been attempted."},{"rthcId":"RPEP-14913","title":"Lithium toxicity following a change from semaglutide to tirzepatide for weight loss management.","authors":"Burson, Jesse R; Leung, Jonathan G","year":2026,"journal":"The mental health clinician, 16(1), 34-38","doi":"10.9740/mhc.2026.02.034","pmid":"41646202","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Switching from semaglutide to tirzepatide precipitated lithium toxicity in a patient with schizoaffective disorder, demonstrating clinically significant pharmacokinetic interactions with GLP-1 RAs.","whyItMatters":"Millions take GLP-1 drugs alongside other medications. This case shows that switching between GLP-1 agents is not pharmacokinetically neutral and requires monitoring.","specificNumbers":"","methodology":"Single case report of lithium toxicity temporally associated with a switch from semaglutide to tirzepatide.","limitations":"Single case report — individual factors may have contributed. The exact pharmacokinetic mechanism is not fully characterized."},{"rthcId":"RPEP-14914","title":"Real-World Experience with Anti-CGRP Pathway Monoclonal Antibodies in a Large United States Healthcare Plan: Results of the Migraine Signature Study.","authors":"Buse, Dawn C; Lipton, Richard B; Urman, Robert; Vaidya, Shruti J; Robinson, Sarah C; Jacobson, Alice S; Scott, Alexandra B; Bensink, Mark E; Pressman, Alice R","year":2026,"journal":"Neurology and therapy, 15(1), 401-420","doi":"10.1007/s40120-025-00872-1","pmid":"41405792","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Real-world data from a large US healthcare plan demonstrates treatment persistence patterns and patient satisfaction with self-injectable anti-CGRP monoclonal antibodies for migraine prevention.","whyItMatters":"Clinical trial results don't always match real-world experience. This study provides the data patients and doctors need to make informed migraine treatment decisions.","specificNumbers":"","methodology":"Observational real-world study (Migraine Signature Study) of patients prescribed ≥1 self-injectable anti-CGRP mAb in a large US healthcare network, measuring persistence and patient-reported outcomes.","limitations":"Observational design — no control group. Self-reported outcomes may have recall bias. Single healthcare plan may not represent all patient populations."},{"rthcId":"RPEP-14915","title":"AAV9-Mimetic Peptides and Electroporation Synergistically Enhance Nanoparticle Transport through the Blood-Brain Barrier.","authors":"Butkovich, Nina; Xu, Yifei; Song, Yuchen; Wang, Lu; Ramirez, Aaron; Li, Enya; Siao, Nikhil Tien Chi; Velazquez-Rivera, Eric; Xiang, Liangzhong; Xu, Xiangmin; Wang, Szu-Wen","year":2026,"journal":"ACS biomaterials science & engineering","doi":"10.1021/acsbiomaterials.5c01483","pmid":"41773824","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"AAV9-derived peptides (AAV.PHP.eB, AAV.X1, AAV.CPP.16) grafted onto nanoparticles synergized with electroporation to enhance BBB transport beyond either approach alone.","whyItMatters":"Brain diseases like Alzheimer's and brain cancers lack effective treatments partly because drugs can't cross the BBB. This dual approach could enable delivery of life-saving therapies.","specificNumbers":"","methodology":"Nanoparticle engineering with AAV9-based surface peptides combined with electroporation, testing BBB transport efficiency in models.","limitations":"Preclinical study — in vivo brain penetration and drug delivery efficacy in disease models not yet demonstrated. Electroporation may have safety concerns."},{"rthcId":"RPEP-14916","title":"Engineering non-ribosomal peptide synthesis: tuning the antibiotics engine of the microbial world.","authors":"Butler, Lucy; Awan, Ali Raza; Ellis, Tom; Akram, Muhammad Safwan","year":2026,"journal":"Critical reviews in biotechnology, 1-21","doi":"10.1080/07388551.2026.2615819","pmid":"41771683","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Synthetic biology and bioengineering approaches are advancing the ability to modify non-ribosomal peptide synthetases for production of novel antimicrobial peptides with pharmaceutical potential.","whyItMatters":"NRPSs produce some of our most important antibiotics (vancomycin, daptomycin). Engineering them could create new antibiotics to combat drug resistance.","specificNumbers":"","methodology":"Review of bioengineering methodologies for modifying non-ribosomal peptide synthetases, including module swapping, yield optimization, and novel peptide design.","limitations":"Review article — many engineering approaches remain technically challenging. Yields from modified NRPSs are often lower than wild-type systems."},{"rthcId":"RPEP-14917","title":"Physical activity promotes gut adaptation, nutrient responsiveness, and sensitivity to gut peptides in male mice.","authors":"Bæch-Laursen, Cecilie; Ucin, Jon Vergara; Galsgaard, Katrine Douglas; Llana, Jesus; Kissow, Hannelouise; Rehfeld, Jens Frederik; Holst, Jens Juul; Pedersen, Bente Klarlund; Sanchis, Paula","year":2026,"journal":"EBioMedicine, 125, 106152","doi":"10.1016/j.ebiom.2026.106152","pmid":"41671865","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Physical activity promotes gut structural adaptation, enhanced nutrient sensing, and increased sensitivity to appetite-regulating gut peptides in mice.","whyItMatters":"Understanding how exercise improves appetite control at the gut level could inform strategies combining exercise with GLP-1 medications for optimal weight management.","specificNumbers":"","methodology":"Preclinical study in C57BL/6NRJ male mice on ad-libitum chow; comparison of active vs. sedentary mice with gut morphology, endocrine function, and central appetite signaling assessment.","limitations":"Mouse model — gut physiology differs from humans; only male mice studied; chow diet may not reflect human eating patterns."},{"rthcId":"RPEP-14918","title":"Antimicrobial peptides in cervical carcinogenesis: Dual roles in tumor progression and emerging therapeutic strategies.","authors":"Błażejczyk, Idalia; Daniluk, Tamara; Toczyłowski, Kacper; Gorbacz-Konończuk, Joanna; Wnorowska, Urszula; Bucki, Robert; Piktel, Ewelina","year":2026,"journal":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 194, 118928","doi":"10.1016/j.biopha.2025.118928","pmid":"41496337","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"AMPs exhibit dual roles in cervical carcinogenesis — both anti-tumorigenic and pro-tumorigenic effects — requiring careful characterization before therapeutic development.","whyItMatters":"Cervical cancer still kills over 300,000 women annually. Understanding AMP dual roles could lead to new therapies while avoiding those that might worsen the disease.","specificNumbers":"","methodology":"Review of antimicrobial peptide biology in cervical cancer, covering dual roles in tumor progression and emerging therapeutic strategies.","limitations":"Review article — no new experimental data. The balance between anti- and pro-tumorigenic effects may vary by cancer stage and specific AMP."},{"rthcId":"RPEP-14919","title":"Spatiotemporal characterization of ghrelin and cholecystokinin levels in the gastrointestinal tract of juvenile Sparus aurata: effects of feeding status and diet composition.","authors":"Caderno, Anyell; Tang, Patrik; de Las Heras, Verónica; Gharbi, Naouel; Alarcón-López, Francisco Javier; Mancera, Juan Miguel; Martos-Sitcha, Juan Antonio; Gilannejad, Neda","year":2026,"journal":"Frontiers in endocrinology, 17, 1734169","doi":"10.3389/fendo.2026.1734169","pmid":"41675571","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Spatiotemporal characterization revealed distinct ghrelin and CCK distribution patterns along the juvenile seabream GIT, with levels responding to feeding status and diet composition.","whyItMatters":"Understanding fish appetite hormones improves aquaculture feeding efficiency, reduces waste, and provides comparative data for understanding mammalian gut hormone biology.","specificNumbers":"","methodology":"Measurement of ghrelin and CCK peptide levels along the GIT of juvenile Sparus aurata under different feeding conditions and diet compositions.","limitations":"Single species (seabream) study — gut hormone distribution may differ in other fish. Juvenile stage only."},{"rthcId":"RPEP-14920","title":"A Machine Learning-Enabled Venom Peptide Platform for Rapid Drug Discovery.","authors":"Cai, Fei; Zhou, Lijuan; Delgado, Bryce; Chang, Wenping; Tom, Jeffrey; Hernandez, Evelyn; Joshi, Prajakta; Song, Aimin; Masureel, Matthieu; Maun, Henry R; Chang, Andrew; Zhang, Yingnan","year":2026,"journal":"Pharmaceuticals (Basel, Switzerland), 19(2)","doi":"10.3390/ph19020288","pmid":"41754828","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A machine learning-enabled venom peptide platform rapidly identifies and optimizes disulfide-stabilized venom peptides targeting GPCRs and ion channels for pharmaceutical development.","whyItMatters":"Venom peptides have already produced important drugs (ziconotide, exenatide). An AI platform to systematically exploit this resource could yield many more.","specificNumbers":"","methodology":"Development of an ML-powered platform for screening, characterizing, and optimizing venom-derived peptides with drug-like properties.","limitations":"Platform validation stage — specific drug candidates from the platform need clinical development. Computational predictions require experimental confirmation."},{"rthcId":"RPEP-14921","title":"Glucagon-like peptide-1 receptor agonists and risk of substance use disorders among US veterans with type 2 diabetes: cohort study.","authors":"Cai, Miao; Choi, Taeyoung; Xie, Yan; Al-Aly, Ziyad","year":2026,"journal":"BMJ (Clinical research ed.), 392, e086886","doi":"10.1136/bmj-2025-086886","pmid":"41781010","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RA initiation was associated with reduced incidence of alcohol, cannabis, cocaine, nicotine, opioid, and other SUDs in veterans without prior addictions, and reduced adverse outcomes in those with pre-existing SUDs.","whyItMatters":"Substance use disorders affect millions and have limited treatments. If GLP-1 drugs reduce addiction risk, they could benefit an enormous population beyond diabetes patients.","specificNumbers":"","methodology":"Target trial emulation using veteran cohort data with two protocols: (1) incident SUD risk in SUD-free veterans, (2) clinical outcomes in veterans with pre-existing SUDs, comparing GLP-1 RA initiators to non-users.","limitations":"Observational study — cannot prove causation. Veterans may not represent the general population. Healthy user bias possible."},{"rthcId":"RPEP-14922","title":"Determination of insulin therapy perceptions in patients with diabetes mellitus and prediabetes attending the diabetes outpatient clinic.","authors":"Cakir, Ahmet; Memis, Hasan; Ozdemir-Ayduran, Nesligül; Tarin, Serenay; Evren, Bahri","year":2026,"journal":"BMC endocrine disorders","doi":"10.1186/s12902-026-02205-1","pmid":"41736002","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Insulin therapy perceptions differ significantly between type 1, type 2, and prediabetic patients, with negative perceptions common across groups and potentially delaying treatment.","whyItMatters":"Negative insulin perceptions delay treatment initiation, leading to worse outcomes. Targeted counseling based on patient type could improve acceptance.","specificNumbers":"","methodology":"Cross-sectional study at a tertiary care hospital (December 2023 onward) assessing insulin therapy perceptions across diabetes types.","limitations":"Single-center study — perceptions may vary by culture, healthcare system, and insurance coverage. Cross-sectional design captures perceptions at one time point."},{"rthcId":"RPEP-14923","title":"AI-powered literature mining reveals the therapeutic significance of GLP-1 receptor: Simulation of natural agonist candidates based on molecular dynamics.","authors":"Cakmak, Rabia Kalkan; Besli, Nail; Ercin, Nilufer; Celik, Ulkan","year":2026,"journal":"Computational biology and chemistry, 121, 108828","doi":"10.1016/j.compbiolchem.2025.108828","pmid":"41389576","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"An AI pipeline integrating BioBERT-based text mining and molecular dynamics simulation identified natural compound candidates as potential GLP-1 receptor agonists.","whyItMatters":"Finding natural GLP-1 receptor activators could provide cheaper, more accessible alternatives to expensive synthetic GLP-1 drugs.","specificNumbers":"","methodology":"AI-integrated drug discovery pipeline using BioBERT biomedical text mining for literature analysis followed by molecular dynamics simulations of natural GLP-1 receptor agonist candidates.","limitations":"Computational study — identified candidates need experimental validation. Natural compounds may have lower potency than synthetic drugs. Literature mining may miss recent or unpublished findings."},{"rthcId":"RPEP-14924","title":"Efficacy of GLP-1 receptor agonists in obese patients with heart failure with preserved ejection fraction: A systematic review and meta-analysis of randomized trials and propensity score-matched cohorts.","authors":"Caldeira Gaelzer, Giulia; Armani Prata, Alonzo; Gustavo Rizzolli, Luís; Mendes Afonso, Luisalice; Lenci Marques, Gustavo","year":2026,"journal":"Current problems in cardiology, 51(1), 103194","doi":"10.1016/j.cpcardiol.2025.103194","pmid":"41173128","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Comprehensive meta-analysis of RCTs and propensity-matched cohorts demonstrates GLP-1 RA efficacy in obese HFpEF patients, with benefits including weight loss and anti-inflammatory effects.","whyItMatters":"Obesity-related HFpEF is the fastest-growing form of heart failure. GLP-1 drugs may uniquely address both the obesity driver and the cardiac consequences.","specificNumbers":"","methodology":"Systematic review and meta-analysis including both randomized controlled trials and propensity score-matched cohort studies of GLP-1 RAs in obese HFpEF patients.","limitations":"Combining RCTs and observational studies introduces heterogeneity. Specific GLP-1 agents may differ in cardiac effects."},{"rthcId":"RPEP-14925","title":"Vitamin D in Infectious Diseases: A Narrative Review Focusing on COVID-19, Long COVID, and Influenza.","authors":"Caliman-Sturdza, Olga Adriana; Gheorghita, Roxana Elena; Soldanescu, Iuliana; Dimian, Mihai; Mangul, Serghei","year":2026,"journal":"Nutrients, 18(4)","doi":"10.3390/nu18040634","pmid":"41754151","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Vitamin D modulates infectious disease outcomes through antimicrobial peptide induction (cathelicidin/LL-37), immune regulation, and anti-inflammatory effects in COVID-19, Long COVID, and influenza.","whyItMatters":"Vitamin D deficiency is extremely common worldwide and easily correctable. If it truly modulates respiratory infection outcomes, supplementation could be a simple, cheap public health intervention.","specificNumbers":"","methodology":"Narrative review of immunological, clinical, and preventive evidence for vitamin D in COVID-19, Long COVID, and influenza.","limitations":"Narrative review — clinical trial evidence for vitamin D in respiratory infections remains inconsistent. Optimal dosing and timing are unclear."},{"rthcId":"RPEP-14926","title":"NPY inhibits vagal activation of NTS catecholamine neurons via presynaptic Y2 receptors in mice.","authors":"Calkins, Rowan J; Zhao, Huan; Page, Stephen J; Neyens, Drew M; Appleyard, Suzanne M","year":2026,"journal":"American journal of physiology. Regulatory, integrative and comparative physiology, 330(3), R283-R299","doi":"10.1152/ajpregu.00315.2024","pmid":"41397282","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"NPY inhibits vagal activation of NTS catecholamine neurons via presynaptic Y2 receptors, providing a mechanism by which NPY modulates gut-derived satiety signaling in the brainstem.","whyItMatters":"Understanding how appetite signals are modulated in the brainstem reveals potential drug targets for obesity treatment and explains why some people have difficulty feeling full.","specificNumbers":"","methodology":"Electrophysiology and pharmacology study in mice examining NPY effects on vagal-NTS synaptic transmission, identifying Y2 receptor-mediated presynaptic inhibition of catecholamine neurons.","limitations":"Mouse study — human brainstem circuitry may differ. In vitro electrophysiology may not fully reflect in vivo conditions."},{"rthcId":"RPEP-14927","title":"Glucagon-Like Peptide-1 Analogues and the Risk of Recurrent Pancreatitis in Diabetic Patients With History of Pancreatitis or Elevated Lipase: Retrospective Cohort Analysis.","authors":"Calvarysky, Bronya; Gal, Yaara; Kushnir, Shiri; Turjeman, Adi; Shochat, Tzippy; Dotan, Idit; Diker Cohen, Talia","year":2026,"journal":"Diabetes/metabolism research and reviews, 42(1), e70116","doi":"10.1002/dmrr.70116","pmid":"41392524","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 analogues were not associated with increased recurrent pancreatitis risk in diabetic patients with prior pancreatitis or elevated lipase, in a cohort of >4.5 million members.","whyItMatters":"Pancreatitis concerns have limited GLP-1 prescribing. Showing safety even in the highest-risk patients removes a major barrier to appropriate use.","specificNumbers":"","methodology":"Retrospective cohort analysis from a large health maintenance organization (>4.5 million members) comparing pancreatitis recurrence in GLP-1 users vs non-users among high-risk patients.","limitations":"Retrospective observational design. Despite large database, the subgroup with prior pancreatitis may still be relatively small. Could not capture unreported mild pancreatitis episodes."},{"rthcId":"RPEP-14928","title":"Bacteriocins in plant pathology: current knowledge, application, challenges and perspectives.","authors":"Caly-Simbou, Eva; Ramin-Mangata, Stéphane; Poussier, Stéphane; Pecrix, Yann","year":2026,"journal":"Biochemical and biophysical research communications, 797, 153203","doi":"10.1016/j.bbrc.2025.153203","pmid":"41455317","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Bacteriocins offer a highly specific, sustainable alternative to chemical pesticides for controlling multi-resistant phytopathogenic bacteria in agriculture.","whyItMatters":"Crop diseases from resistant bacteria threaten global food security. Bacteriocins could provide targeted treatment without the environmental damage of broad-spectrum pesticides.","specificNumbers":"","methodology":"Review of bacteriocin biology, current applications, challenges, and future perspectives for plant pathology and crop protection.","limitations":"Review article — many agricultural bacteriocin applications are still experimental. Field-scale production, stability, and delivery remain challenging."},{"rthcId":"RPEP-14929","title":"Tirzepatide-Associated Euglycemic Diabetic Ketoacidosis in the Absence of Sodium-Glucose Cotransporter-2 Inhibitor Use: A Case Report.","authors":"Campana, Christina; Heaney, Ashley; Ceraolo, Negin; Srinivas, Surbhi; Simon, Erin L","year":2026,"journal":"The Journal of emergency medicine, 83, 57-60","doi":"10.1016/j.jemermed.2026.01.002","pmid":"41747466","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"EDKA occurred in a patient on tirzepatide monotherapy without concurrent SGLT-2 inhibitor use, suggesting GLP-1/GIP agonists may independently precipitate this rare condition.","whyItMatters":"EDKA is life-threatening and easily missed because blood sugar appears normal. Clinicians need to know it can occur with tirzepatide even without SGLT-2 inhibitors.","specificNumbers":"","methodology":"Single case report of euglycemic DKA in a patient on tirzepatide monotherapy.","limitations":"Single case report — cannot establish incidence rate. Individual patient factors (fasting, illness, dehydration) may have contributed."},{"rthcId":"RPEP-14930","title":"IGF-I bioavailability in congenital isolated growth hormone deficiency.","authors":"Campos, Viviane C; Aguiar Oliveira, Manuel H; Bidlingmaier, Martin; Yuen, Kevin C J; Salvatori, Roberto; Oliveira, Carla R P; Leal, Angela; Melo, Enaldo; Schilbach, Katharina; Frystyk, Jan; Schweizer, Júnia R O L","year":2026,"journal":"European journal of endocrinology, 194(2), 136-145","doi":"10.1093/ejendo/lvag007","pmid":"41528724","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Congenital isolated GH-deficient individuals show severely reduced IGF-I and IGFBP-3 but altered IGF-I bioavailability, associated with no premature atherosclerosis and normal lifespan despite metabolic risk factors.","whyItMatters":"Understanding why GH-deficient people avoid heart disease despite metabolic risk factors could reveal new pathways for cardiovascular protection in the general population.","specificNumbers":"","methodology":"Characterization of IGF-I bioavailability in the Itabaianinha cohort with homozygous GHRH receptor mutation causing congenital isolated GH deficiency.","limitations":"Unique genetic cohort — findings may not generalize to acquired GH deficiency or GH-normal populations. Small cohort inherent to rare genetic condition."},{"rthcId":"RPEP-14931","title":"Influence of GLP1 receptor rs6923761 and rs761387 genetic variants on oral semaglutide response in patients with type 2 diabetes.","authors":"Candido, Riccardo; Toffoli, Barbara; Baccichetto, Gabriele; Marchese, Francesca; Carpenè, Silvia; Gaiotti, Sara; Fabris, Bruno; Bernardi, Stella","year":2026,"journal":"Acta diabetologica, 63(2), 303-311","doi":"10.1007/s00592-025-02626-9","pmid":"41307691","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP1R polymorphisms rs6923761 and rs761387 significantly influenced clinical response to oral semaglutide in a retrospective cohort of T2DM patients.","whyItMatters":"Pharmacogenomics could allow personalized GLP-1 drug prescribing, ensuring patients receive the medication most likely to work for their genetic profile.","specificNumbers":"","methodology":"Retrospective cohort study of adult T2DM patients on oral semaglutide, genotyped for GLP1R rs6923761 and rs761387 polymorphisms and assessed for treatment response.","limitations":"Retrospective design with likely modest sample size. Single oral formulation studied — results may not apply to injectable semaglutide. Ethnic/population genetics may vary."},{"rthcId":"RPEP-14932","title":"Heart failure with reduced ejection fraction.","authors":"Cannata, Antonio; Crespo-Leiro, Maria Generosa; Bromage, Daniel I; Ruschitzka, Frank; McDonagh, Theresa A","year":2026,"journal":"Lancet (London, England), 407(10527), 529-542","doi":"10.1016/S0140-6736(25)01851-3","pmid":"41319669","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"HFrEF accounts for approximately half of all heart failure cases, with diagnosis relying on natriuretic peptide levels, cardiac imaging, and clinical signs/symptoms.","whyItMatters":"HFrEF affects 70 million people globally and is a leading cause of hospitalization, disability, and death. Evidence-based treatment can significantly improve outcomes.","specificNumbers":"","methodology":"Comprehensive clinical review of heart failure with reduced ejection fraction epidemiology, diagnosis, and management.","limitations":"Review article — provides overview rather than new data. Treatment recommendations may evolve as new evidence emerges."},{"rthcId":"RPEP-14933","title":"Nociceptive neuroimmune circuit drives immune evasion.","authors":"Cao, Canhui","year":2026,"journal":"Trends in cancer","doi":"10.1016/j.trecan.2026.01.003","pmid":"41775602","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tumors hijack an interorgan nociceptor-SLIT2-CGRP neural circuit to drive systemic immunosuppression, and disrupting this loop restores T-cell function and enhances immunotherapy efficacy.","whyItMatters":"Understanding how tumors use the nervous system to escape immunity could lead to entirely new cancer treatments that combine nerve-blocking drugs with immunotherapy.","specificNumbers":"","methodology":"Research commentary on the discovery of a tumor-exploited nociceptor-SLIT2-CGRP circuit that mediates immune evasion, with experimental disruption restoring anti-tumor immunity.","limitations":"Commentary on primary research — specific experimental details in the original study. Translation to human tumors needs validation."},{"rthcId":"RPEP-14934","title":"Adaptation of plateau frog peptide: From antimicrobial to angiogenic and proliferative functions.","authors":"Cao, Kaixun; Zhang, Liting; Yang, Min; Gao, Jinai; Deng, Congshuang; Huang, Xiaoshan; Chen, Qian; Lu, Qiumin; Cheng, Yizhe; Gao, Shaoyang; Cao, Hui; Lai, Ren","year":2026,"journal":"Journal of advanced research, 81, 287-300","doi":"10.1016/j.jare.2025.06.013","pmid":"40490151","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"SC17-2 peptide from high-altitude frog N. parkeri evolved from antimicrobial to angiogenic and cell migration-promoting functions, representing adaptation to extreme UV environments on the Tibetan Plateau.","whyItMatters":"Understanding how evolution repurposes antimicrobial peptides reveals new bioactive molecules with wound-healing potential that would never be found by traditional drug screening.","specificNumbers":"","methodology":"Functional characterization of SC17-2 peptide investigating angiogenesis, cell migration, and adaptation to high-UV environments, compared to typical antimicrobial frog peptides.","limitations":"Single peptide from one species. In vitro functional assays — in vivo wound healing not tested. Mechanism of functional evolution not fully characterized."},{"rthcId":"RPEP-14935","title":"The association between glucagon-like peptide-1 receptor agonists and reported musculoskeletal adverse events: a systematic review and meta-analysis of randomized controlled trials.","authors":"Cao, Meng; Lin, Chu; Cai, Xiaoling; Lv, Fang; Yang, Wenjia; Ji, Linong","year":2026,"journal":"Therapeutic advances in musculoskeletal disease, 18, 1759720X261428147","doi":"10.1177/1759720X261428147","pmid":"41782908","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Systematic review and meta-analysis of RCT safety data evaluates the association between GLP-1 RA use and spontaneous reports of musculoskeletal adverse events.","whyItMatters":"Millions take GLP-1 drugs, and muscle/joint complaints are common patient concerns. Evidence-based safety data helps clinicians provide informed counseling.","specificNumbers":"","methodology":"Systematic review and meta-analysis of randomized controlled trials assessing musculoskeletal adverse event reports in GLP-1 RA-treated patients.","limitations":"Relies on spontaneous adverse event reporting in RCTs, which may undercount real-world events. Different musculoskeletal conditions may have different risk profiles."},{"rthcId":"RPEP-14936","title":"Additive effects of GLY-200 (oral pharmacologic duodenal exclusion therapy) and GLP-1R agonist in obesity management.","authors":"Carlson, Taylor L; Fineman, Mark; Kernodle, Stace; Hutch, Chelsea R; Bryant, Christine; Colbert, Kevin; Seeley, Randy J; Nimgaonkar, Ashish","year":2026,"journal":"Molecular metabolism, 103, 102287","doi":"10.1016/j.molmet.2025.102287","pmid":"41270831","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLY-200, an oral non-absorbed polymeric drug emulating duodenal exclusion, showed additive metabolic and weight loss effects when combined with GLP-1 receptor agonists.","whyItMatters":"Adding a complementary oral drug to GLP-1 therapy could achieve greater weight loss without increasing injection burden or surgical risk.","specificNumbers":"","methodology":"Evaluation of GLY-200 combined with GLP-1 RA for additive effects on weight loss and metabolic parameters in obesity management.","limitations":"Investigational drug — not yet approved. Long-term safety and efficacy data needed. Mechanism of duodenal exclusion mimicry not fully characterized."},{"rthcId":"RPEP-14937","title":"Glucagon-like peptide-1 receptor agonist semaglutide through the lens of psychiatry: a systematic review of potential benefits and risks.","authors":"Carminati, Matteo; Tondello, Mattia; Concina, Arianna; Olgiati, Paolo; Zanardi, Raffaella","year":2026,"journal":"International clinical psychopharmacology, 41(2), 77-95","doi":"10.1097/YIC.0000000000000595","pmid":"40577093","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide demonstrates potential neuroprotective effects but may influence psychological functioning, with reports of psychopathological symptoms including mood changes in some patients.","whyItMatters":"Tens of millions take semaglutide. Understanding its psychiatric profile helps clinicians monitor patients and manage expectations about mental health effects.","specificNumbers":"","methodology":"Systematic review searching PubMed and Google Scholar for studies on semaglutide's effects on mental health and neuropsychiatric outcomes.","limitations":"Systematic review quality depends on available primary studies. Distinguishing drug effects from weight loss-related mood changes is difficult."},{"rthcId":"RPEP-14938","title":"Redefining Therapies for Drug-Resistant Tuberculosis: Synergistic Effects of Antimicrobial Peptides, Nanotechnology, and Computational Design.","authors":"Carnero Canales, Christian S; Marquez Cazorla, Jessica Ingrid; Marquez Cazorla, Renzo Marianito; Santos, Aline Martins Dos; Lobato Duarte, Jonatas; Oliveira Catarin Nunes, Letícia; Reis, Túlio Custódio; Cerazi Salvador, Lara; Santos-Filho, Norival Alves; Sábio, Rafael Miguel; Santos, Hélder A; Pavan, Fernando Rogério","year":2026,"journal":"Advanced healthcare materials, e03964","doi":"10.1002/adhm.202503964","pmid":"41549858","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The synergy of antimicrobial peptides, nanotechnology delivery systems, and computational design offers promising new therapeutic strategies against MDR and XDR tuberculosis.","whyItMatters":"MDR-TB has a 50% treatment success rate. New approaches combining peptides, nanotech, and AI could dramatically improve outcomes for the world's deadliest bacterial infection.","specificNumbers":"","methodology":"Review of antimicrobial peptide, nanotechnology, and computational design approaches for drug-resistant TB treatment.","limitations":"Review article — most combined approaches remain in preclinical development. Translating nanoparticle-peptide systems to TB patients is technically challenging."},{"rthcId":"RPEP-14939","title":"Long-Term Effectiveness and Persistence Factors of Anti-CGRP Monoclonal Antibodies in Migraine: 2-Year Results From the EUREkA Cohort.","authors":"Caronna, Edoardo; Mas-de-Les-Valls, Rut; Egeo, Gabriella; Millán Vázquez, Manuel; Nieves-Castellanos, Candela; Portocarrero-Sánchez, Leonardo; Vaghi, Gloria; Rodríguez-Montolio, Joana; Jaimes, Alex; Muñoz-Vendrell, Albert; Oliveira, Renato; Polanco, Marcos; González Osorio, Yesica; Canales, Javiera; Ornello, Raffaele; Thunstedt, Cem; Fernández-Lázaro, Iris; Husøy, Andreas; Sánchez-Soblechero, Antonio; Nunes Vicente, Beatriz; Riesco, Nuria; Flores Pina, Belén; Fernandes, Catarina; Lopez, Alberto Andres; Martins-Silva, Elisa; Budrewicz, Sławomir; Gallardo, Víctor José; Gómez Dabó, Laura; Torres-Ferrus, Marta; Alpuente, Alicia; Torelli, Paola; Aurilia, Cinzia; Lamas, Raquel; Ruiz Castrillo, Maria José; De Icco, Roberto; Sances, Grazia; Broadhurst, Sarah; Winstanley, Jed; Gómez, Andrea; Campoy, Sergio; Marques, Inês; Parreira, Elsa; Gárate, Gabriel; Pascual, Julio; Guerrero Peral, Angel Luis; Caponnetto, Valeria; Straube, Andreas; Gonzalez-Martinez, Alicia; Quintas, Sonia; Sánchez-Del-Río, Margarita; Tronvik, Erling; Venegas Pérez, Begoña; Oterino Duran, Agustín; Rodrigues, Miguel; Cevoli, Sabina; Colombo, Bruno; Trimboli, Michele; Frediani, Fabio; d'Onofrio, Florindo; Aguggia, Marco; Salerno, Antonio; Carnevale, Antonio; Zucco, Maurizio; Albanese, Maria; Finocchi, Cinzia; Ranieri, Angelo; Zoroddu, Francesco; Autunno, Massimo; Sanahuja, Jordi; Waliszewska-Prosół, Marta; Pereira, Liliana; Layos-Romero, Almudena; Luzeiro, Isabel; Dorado, Laura; Alvarez-Escudero, Rocio; Martins, Isabel Pavao; Sundal, Christina; Irimia, Pablo; Lozano Ros, Alberto; Gago-Veiga, Ana Beatriz; Juanes, Fernando Velasco; Ruscheweyh, Ruth; Sacco, Simona; García-Azorín, David; González-Quintanilla, Vicente; Gil-Gouveia, Raquel Santos; Huerta Villanueva, Mariano; Rodríguez-Vico, Jaime; Lasaosa, Sonia Santos; Ghadri-Sani, Mona; Tassorelli, Cristina; Díaz De Terán Velasco, Francisco Javier; Diaz-Insa, Samuel; González Oria, Carmen; Barbanti, Piero; Pozo-Rosich, Patricia","year":2026,"journal":"Neurology, 106(4), e214659","doi":"10.1212/WNL.0000000000214659","pmid":"41604607","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Anti-CGRP monoclonal antibodies demonstrated sustained effectiveness at 24 months with significant reduction in monthly headache days, and baseline factors predicting 2-year treatment persistence were identified.","whyItMatters":"Long-term effectiveness data justifies continued insurance coverage and helps patients commit to treatment knowing it maintains efficacy over 2 years.","specificNumbers":"","methodology":"Prospective observational multicenter registry study (EUREkA cohort) analyzing anti-CGRP MAb effectiveness and persistence factors at 24 months.","limitations":"Observational registry — no control group. Survivor bias may inflate effectiveness if non-responders dropped out early."},{"rthcId":"RPEP-14940","title":"Dendropsophin 1, an antimicrobial peptide from skin secretion of the tree frog Dendropsophus columbianus, exhibits tissue repair potential.","authors":"Cassimiro, Isabella S; Ferreira, Bruno A; Deconte, Simone R; Lima, Taís C; Moura, Francyelle B R; Castro, Mariana S; Araújo, Fernanda A","year":2026,"journal":"Toxicon : official journal of the International Society on Toxinology, 271, 108963","doi":"10.1016/j.toxicon.2025.108963","pmid":"41412217","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Dc1 antimicrobial peptide from D. columbianus frog skin demonstrates immunomodulatory and tissue repair potential in addition to its established antimicrobial activity.","whyItMatters":"Chronic wounds affect millions and need treatments that both fight infection and promote healing. A single peptide doing both is therapeutically ideal.","specificNumbers":"","methodology":"Characterization of immunomodulatory and tissue repair properties of Dendropsophin 1 beyond its previously described antimicrobial effects.","limitations":"In vitro characterization — in vivo wound healing not tested. Peptide stability and delivery for clinical use need development."},{"rthcId":"RPEP-14941","title":"Study of Human Antimicrobial Peptides Active Against Some Bacteroidota Species of the Oral Cavity.","authors":"Castagliuolo, Giusy; Notomista, Eugenio; Sordillo, Alessia; Barone, Laura; Antonini, Dario; Renzi, Francesco; Zanfardino, Anna; Varcamonti, Mario","year":2026,"journal":"Antibiotics (Basel, Switzerland), 15(1)","doi":"10.3390/antibiotics15010080","pmid":"41594117","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Bioinformatically selected human AMPs demonstrated antimicrobial activity against Bacteroidota species associated with oral disease, suggesting potential alternatives to conventional antibiotics for periodontal infections.","whyItMatters":"Periodontal disease affects nearly half of adults and is linked to systemic conditions. AMPs from our own bodies could treat oral infections with fewer resistance concerns.","specificNumbers":"","methodology":"Bioinformatic selection of human AMPs followed by antimicrobial activity testing against oral Bacteroidota species.","limitations":"In vitro testing — oral biofilm environment is much more complex. Peptide stability in saliva and the oral cavity needs evaluation."},{"rthcId":"RPEP-14942","title":"Exploring the Potential Link Between Tirzepatide and Non-Arteritic Anterior Ischemic Optic Neuropathy (NAION): Evidence from FAERS and Google Trends.","authors":"Castellana, Eleonora; Chiappetta, Maria Rachele","year":2026,"journal":"Hospital pharmacy, 00185787251403040","doi":"10.1177/00185787251403040","pmid":"41509894","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"FAERS analysis and Google Trends data reveal a potential safety signal linking tirzepatide to NAION, warranting further pharmacovigilance and clinical investigation.","whyItMatters":"NAION can cause permanent vision loss. As tirzepatide prescriptions grow rapidly, even rare eye complications affect thousands of patients.","specificNumbers":"","methodology":"Pharmacovigilance analysis of FAERS adverse event reports combined with Google Trends analysis for NAION-related search patterns associated with tirzepatide use.","limitations":"FAERS reports are voluntary and subject to reporting bias. Google Trends correlations cannot establish causation. NAION has many risk factors independent of medication use."},{"rthcId":"RPEP-14943","title":"Overview of Diabetes Medications: Traditional and New-Generation Agents and Their Off-Label Use for Weight Loss.","authors":"Castellana, Eleonora; Budau, Patricia Madalina; Chiappetta, Maria Rachele","year":2026,"journal":"The Journal of pharmacy technology : jPT : official publication of the Association of Pharmacy Technicians, 87551225261422610","doi":"10.1177/87551225261422610","pmid":"41743493","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Comprehensive review of traditional and new-generation diabetes agents documents expanding off-label weight loss use driven by GLP-1 RA efficacy and the growing overlap between diabetes and obesity treatment.","whyItMatters":"Many patients use diabetes drugs off-label for weight loss. Understanding the evidence and risks across all medication classes helps guide safe prescribing.","specificNumbers":"","methodology":"Narrative review of diabetes medications including traditional agents, new-generation therapies, and off-label weight management applications.","limitations":"Narrative review — not a systematic analysis. Off-label use evidence is less rigorous than approved-indication data."},{"rthcId":"RPEP-14944","title":"Targeting peptide homes to spinal cord injury in a rat model.","authors":"Castillo, Jose A; Le, Michael Nhien; Huang, Kuan-Wei; Pivetti, Christopher; Vatoofy, Sina; Ratcliff, Amanda; Tran, Taylor; Bannerman, Solomon; Lee, Maya; Shahin, Mehrad; Loll, Emma; Clark, Kaitlin; Reynolds, Elizabeth; Dangan, Andrei M T; Uppuluri, Jay; Urreola, Gabriel; Wang, Aijun A; Russo, Rachel M","year":2026,"journal":"The journal of trauma and acute care surgery, 100(2), 198-205","doi":"10.1097/TA.0000000000004819","pmid":"41247331","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CAQK selectively accumulated at the spinal cord injury site after intravenous injection, demonstrating dose-dependent targeting with the medium dose (1.0 mg/kg) showing optimal localization.","whyItMatters":"Spinal cord injuries are devastating and current treatments lack precision. A peptide that can specifically find and deliver drugs to the exact injury site could dramatically improve therapy while reducing side effects.","specificNumbers":"","methodology":"Preclinical animal study using 24 rats with C6 spinal cord hemicontusion injuries, testing fluorescently labeled CAQK at three doses via tail vein injection with tissue analysis.","limitations":"Small animal model (rats) that may not translate directly to humans; only tested in acute injury settings; did not evaluate therapeutic cargo delivery or functional recovery outcomes."},{"rthcId":"RPEP-14945","title":"Neuropeptide Y regulation of dental pulp neurogenic inflammation provoked by tooth bleaching agents: a descriptive comparative clinical study.","authors":"Caviedes-Bucheli, Javier; Ríos-Osorio, Néstor; Pérez-Villota, Mario; Aucú-Miño, Karolina; Escobar-Mafla, Diana; Muñoz-Alvear, Hernán Darío; Gomez-Sosa, José Francisco; Diaz-Barrera, Luis; Güiza-Cristancho, Edgar; Munoz, Hugo Roberto","year":2026,"journal":"Restorative dentistry & endodontics, 51(1), e10","doi":"10.5395/rde.2026.51.e10","pmid":"41680589","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tooth bleaching with hydrogen peroxide-based systems altered neuropeptide Y levels in dental pulp, with differences between the three commercial systems tested, suggesting NPY plays a role in post-bleaching inflammation and sensitivity.","whyItMatters":"Tooth sensitivity after professional whitening is extremely common and poorly understood at the molecular level. Understanding how NPY mediates this inflammatory response could lead to better prevention strategies.","specificNumbers":"","methodology":"Descriptive comparative clinical study with 40 premolar pulps divided into 4 groups (n=10 each), analyzed via ELISA for NPY quantification after exposure to different bleaching protocols.","limitations":"Relatively small sample size per group (n=10); only measured NPY at one time point after bleaching; used extracted teeth rather than in vivo monitoring; did not correlate NPY levels with patient-reported pain."},{"rthcId":"RPEP-14946","title":"Could galcanezumab modulate inflammatory cytokines? A single-centre exploratory study.","authors":"Ceccardi, Giulia; Rao, Renata; Schiano di Cola, Francesca; Fiducia, Beatrice; Tolassi, Chiara; Quaresima, Virginia; Mattioli, Irene; Eshja, Klaudia; Cresta, Elena; Gipponi, Stefano; Pilotto, Andrea; Padovani, Alessandro","year":2026,"journal":"Journal of neurology, 273(2)","doi":"10.1007/s00415-026-13706-3","pmid":"41735672","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Galcanezumab treatment was associated with changes in inflammatory cytokine profiles in migraine patients, suggesting the drug may have anti-inflammatory effects beyond CGRP blockade.","whyItMatters":"Not all migraine patients respond to CGRP-targeted drugs. If galcanezumab also reduces inflammation, it could help identify which patients will benefit most and potentially expand its therapeutic applications.","specificNumbers":"","methodology":"Single-centre exploratory clinical study measuring cytokine profiles in episodic and chronic migraine patients before and during galcanezumab treatment.","limitations":"Exploratory single-centre design limits generalizability; likely small sample size; correlation between cytokine changes and clinical improvement not definitively established."},{"rthcId":"RPEP-14947","title":"GLP-1 Receptor Analogs: Evidence Linking to Effect on Metabolic and Reproductive Functions in Patients with PCOS and Obesity.","authors":"Celik, Ozlem; Yazici, Dilek; Ciudin, Andreea; Macut, Djuro; Micic, Dragan; Yumuk, Volkan; Yildiz, Bulent Okan","year":2026,"journal":"Obesity facts, 19(1), 93-108","doi":"10.1159/000547055","pmid":"40743996","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 receptor analogs demonstrate evidence of improving both metabolic dysfunction (insulin resistance, weight) and reproductive outcomes (androgen levels, ovulation) in women with PCOS and obesity.","whyItMatters":"PCOS affects up to 13% of reproductive-age women, and obesity makes it worse. If GLP-1 drugs can address both the weight and hormonal components simultaneously, it could transform PCOS management.","specificNumbers":"","methodology":"Evidence review/synthesis examining clinical data linking GLP-1 receptor analog therapy to metabolic and reproductive outcomes in PCOS patients with obesity.","limitations":"Review article rather than original clinical trial; GLP-1 drugs are not yet approved specifically for PCOS; long-term reproductive safety data in this population is limited."},{"rthcId":"RPEP-14948","title":"World Health Organization Guideline on the Use and Indications of Glucagon-Like Peptide-1 Therapies for the Treatment of Obesity in Adults.","authors":"Celletti, Francesca; Farrar, Jeremy; De Regil, Luz","year":2026,"journal":"JAMA, 335(5), 434-438","doi":"10.1001/jama.2025.24288","pmid":"41324410","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"WHO now formally recommends GLP-1 therapies as part of integrated, person-centered obesity treatment, recognizing obesity as a chronic disease requiring lifelong management beyond behavioral interventions alone.","whyItMatters":"WHO guidelines shape healthcare policy worldwide. Their endorsement of GLP-1 drugs for obesity legitimizes pharmacotherapy as a standard treatment approach and could improve access globally, especially in countries that have been slow to adopt these treatments.","specificNumbers":"","methodology":"WHO clinical practice guideline developed through systematic evidence review and Member State consultation.","limitations":"Guidelines may face implementation challenges in low-resource settings where GLP-1 drugs are expensive or unavailable; does not resolve supply shortages or affordability concerns."},{"rthcId":"RPEP-14949","title":"European sea bass beta-defensins are regulated by betanodavirus infection and show direct antiviral and antibacterial functions.","authors":"Cervera, Laura; Valero, Yulema; Hernández-Ariola, Elena; Cárdenas, Constanza; Guzman, Fanny; Mercado, Luis; Chaves-Pozo, Elena; Cuesta, Alberto","year":2026,"journal":"Fish & shellfish immunology, 169, 111048","doi":"10.1016/j.fsi.2025.111048","pmid":"41319888","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"European sea bass beta-defensins (bdef1 and bdef2) are upregulated by betanodavirus infection and possess direct antiviral activity in addition to their known antibacterial functions.","whyItMatters":"Understanding fish antimicrobial peptides helps develop disease-resistant aquaculture stocks and may reveal conserved immune mechanisms relevant to human defensin biology and peptide-based therapeutics.","specificNumbers":"","methodology":"Laboratory study examining gene regulation, protein expression, and functional assays of beta-defensins in European sea bass during viral infection.","limitations":"In vitro functional assays may not fully reflect in vivo immune dynamics; single fish species studied; redox state effects on function need further characterization."},{"rthcId":"RPEP-14950","title":"Impact of Semaglutide on Limb Events: A Meta-Analysis of Randomized Controlled Trials.","authors":"Cesaro, Arturo; Acerbo, Vincenzo; Longo, Miriam; Antonucci, Alessandra; Maiorino, Maria Ida; Monaco, Maria Grazia; Martelli, Eugenio; Giudice, Giorgio; Esposito, Katherine; Giorgino, Francesco; Federici, Massimo; Calabrò, Paolo","year":2026,"journal":"European journal of preventive cardiology","doi":"10.1093/eurjpc/zwag077","pmid":"41662383","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The pooled analysis of 19 RCTs with 51,557 participants assessed semaglutide's impact on peripheral limb events, providing the most comprehensive evidence to date on this important but understudied outcome.","whyItMatters":"PAD affects millions of people with diabetes and can lead to amputation. If semaglutide protects limbs in addition to the heart, it could prevent devastating complications that dramatically reduce quality of life.","specificNumbers":"","methodology":"Systematic review and meta-analysis of 19 randomized controlled trials following PRISMA guidelines, pooling data from 51,557 participants.","limitations":"Limb events were typically secondary endpoints in the included trials; heterogeneity in how limb events were defined and reported across studies; follow-up durations may have been insufficient to capture all limb outcomes."},{"rthcId":"RPEP-14951","title":"Fermented Plant-Based Foods and Postbiotics for Glycemic Control-Microbial Biotransformation of Phytochemicals.","authors":"Cevallos-Fernández, Emilia; Beltrán-Sinchiguano, Elena; Jácome, Belén; Quintana, Tatiana; Rivera, Nadya","year":2026,"journal":"Molecules (Basel, Switzerland), 31(2)","doi":"10.3390/molecules31020360","pmid":"41599407","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Microbial fermentation of plant foods produces bioactive compounds including peptides and transformed polyphenols that improve glycemic control through multiple pathways including enhanced GLP-1 signaling and insulin sensitivity.","whyItMatters":"Fermented foods are affordable, widely available, and culturally embedded worldwide. Understanding their glycemic benefits at a molecular level could provide accessible dietary strategies for the growing diabetes epidemic.","specificNumbers":"","methodology":"Narrative review synthesizing mechanistic, preclinical, and human clinical data across multiple fermented food categories.","limitations":"Narrative review format rather than systematic review; most evidence is mechanistic or preclinical; human clinical trials are limited and heterogeneous; fermented food composition varies widely."},{"rthcId":"RPEP-14952","title":"Trimethylamine-N-Oxide as a Novel Biomarker in Acute Decompensated Heart Failure: A Comparative Study With Stable Heart Failure Patients.","authors":"Ceylan, Yemlihan; Kaya, Muhammed; Saygın, Murat; Alp, Hamit Hakan","year":2026,"journal":"Angiology, 77(4), 448-457","doi":"10.1177/00033197251384351","pmid":"41147212","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"TMAO had a higher AUC than BNP for discriminating acute decompensated from stable heart failure, establishing it as a potential novel biomarker for detecting heart failure worsening.","whyItMatters":"Quickly identifying acute heart failure decompensation saves lives. If TMAO outperforms the current gold standard (BNP), it could improve emergency diagnosis and help guide treatment urgency.","specificNumbers":"","methodology":"Prospective observational study with 162 participants (102 ADHF, 60 SHF), comparing plasma TMAO levels with clinical, echocardiographic, and laboratory parameters.","limitations":"Observational study cannot establish causation; moderate sample size; TMAO levels can be influenced by diet and kidney function, which may confound results."},{"rthcId":"RPEP-14953","title":"Cathelicidin-Ka, the first frog-derived TLR2 and TLR4 agonist, induces macrophage activation and promotes inflammation.","authors":"Chai, Jinwei; Wu, Jiena; Zhang, Shuiying; Zhang, Wenjun; Xiong, Weichen; Li, Jinqiao; Nguyen, Tienthanh; Shu, Lixia; Kotsyfakis, Michail; Chen, Xin; Xu, Xueqing","year":2026,"journal":"Cellular and molecular life sciences : CMLS, 83(1), 83","doi":"10.1007/s00018-025-06068-y","pmid":"41540150","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Cath-Ka is the first identified frog-derived TLR2/TLR4 agonist that activates macrophage antimicrobial functions through the MyD88 signaling pathway, enhancing bacterial killing.","whyItMatters":"TLR-targeted immunotherapy is a promising approach to fighting infections, especially antibiotic-resistant ones. Discovering new TLR agonists from natural sources expands the toolkit for developing immune-boosting treatments.","specificNumbers":"","methodology":"In vitro immunology study isolating Cath-Ka from frog skin and testing its effects on macrophage activation, signaling pathways, and antibacterial function.","limitations":"In vitro study only — in vivo efficacy and safety not yet demonstrated; pro-inflammatory effects could be problematic if not properly controlled in a therapeutic setting."},{"rthcId":"RPEP-14954","title":"Effects of CT-388, a once-weekly signaling-biased dual GLP-1/GIP receptor agonist, on weight loss and glycemic control in preclinical models and participants with obesity.","authors":"Chakravarthy, Manu V; Rodriguez, Ruben; Hergarden, Anne; Elliott, Michael A; Frias, Juan P; Argüelles-Tello, Federico A; Tenorio, Edgar; Rankin, Jonathan E; Wu, Jingtao; Krishnan, Shyam; Erlanson, Daniel A; Fucini, Raymond V; Bone, Derek; Iwig, Jeffrey S; Acosta, Luis; Untereiner, Ashley; Pant, Asmita; Patton, Avalon; Sanchez-Sanchez, Leyla L; Luo, Jian; Steinberg, Alexandra; Bialonczyk, Damian; Hansen, Stig K","year":2026,"journal":"Molecular metabolism, 103, 102291","doi":"10.1016/j.molmet.2025.102291","pmid":"41319798","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Signal-biased dual GLP-1/GIP receptor agonism with CT-388 produced superior weight loss compared to unbiased agonism in preclinical models, with supportive early clinical data in obesity.","whyItMatters":"If biased signaling truly delivers better weight loss outcomes, CT-388 could outperform current dual-agonist drugs like tirzepatide, raising the bar for obesity pharmacotherapy.","specificNumbers":"","methodology":"Combined preclinical (cell-based assays and animal models) and early clinical study in participants with obesity evaluating CT-388 efficacy.","limitations":"Very early clinical data (likely phase 1); preclinical advantages don't always translate to humans; long-term safety profile unknown."},{"rthcId":"RPEP-14955","title":"Efficacy and safety of CT-868, a novel, fully biased, dual glucagon-like peptide-1/glucose-dependent insulinotropic polypeptide receptor agonist, in type 2 diabetes: A double-blind, randomized placebo controlled phase 2 trial.","authors":"Chakravarthy, Manu V; Elliott, Michael A; Acosta, Luis; Sonnenberg, Gabriele E; Bialonczyk, Damian; Wu, Jingtao; Argüelles-Tello, Federico A; Garcia-Reza, Raymundo; González-González, José Gerardo; Hansen, Stig K; Frias, Juan P","year":2026,"journal":"Diabetes, obesity & metabolism, 28(3), 1673-1682","doi":"10.1111/dom.70006","pmid":"40762050","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CT-868 demonstrated glycemic efficacy as a signal-biased dual GLP-1/GIP agonist in type 2 diabetes, with both dose levels showing HbA1c improvements over 26 weeks.","whyItMatters":"CT-868 represents a new approach to dual-incretin therapy with biased signaling that could offer different efficacy/tolerability profiles compared to tirzepatide, potentially expanding treatment options for type 2 diabetes.","specificNumbers":"","methodology":"Phase 2 randomized, double-blind, placebo-controlled trial; 26 weeks; adults with T2D and BMI ≥27; randomized 1:2:1 to CT-868 1.75 mg, 4.0 mg, or placebo.","limitations":"COVID-19 supply issues affected dosing in some participants; phase 2 trial with likely moderate sample size; long-term safety and efficacy beyond 26 weeks unknown."},{"rthcId":"RPEP-14956","title":"Glycaemic control remains central in type 2 diabetes mellitus management: key learnings from the latest International Diabetes Federation guidelines.","authors":"Chan, Juliana C N; Deerochanawong, Chaicharn; Khunti, Kamlesh; Hassanein, Mohamed; Mohan, Viswanathan","year":2026,"journal":"Diabetes research and clinical practice, 234, 113173","doi":"10.1016/j.diabres.2026.113173","pmid":"41722868","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The IDF guidelines reaffirm glycemic control as the cornerstone of T2D management while recognizing SGLT2i and GLP-1 RA cardiovascular-kidney benefits, particularly emphasizing equitable access in LMICs.","whyItMatters":"Global diabetes guidelines must balance cutting-edge drug evidence with the reality that most patients worldwide cannot access expensive new medications, making practical glycemic control strategies essential.","specificNumbers":"","methodology":"Expert panel discussion and analysis of the 2025 IDF clinical practice guidelines based on randomized trial evidence.","limitations":"Guidelines reflect expert consensus which may lag behind emerging evidence; implementation challenges in LMICs are acknowledged but not fully addressed."},{"rthcId":"RPEP-14957","title":"GLP-1 receptor agonist use during immune checkpoint inhibitor therapy is associated with mortality and Immune-Related adverse events across cancer types in People with type 2 Diabetes: A Target-Trial emulation.","authors":"Chan, Shan-Ho; Li, Pei-Yun; Li, Pin-Hung; Lin, Yu-Jung; Wang, Wei-Hsun; Huang, Yu-Nan; Chen, Jia-Yuh","year":2026,"journal":"Diabetes research and clinical practice, 231, 113073","doi":"10.1016/j.diabres.2025.113073","pmid":"41453566","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Concurrent GLP-1 receptor agonist use at immune checkpoint inhibitor initiation was associated with mortality and immune-related adverse events in cancer patients with type 2 diabetes.","whyItMatters":"Millions of patients now take GLP-1 drugs for diabetes or weight loss. As cancer immunotherapy expands, understanding drug interactions between these two major medication classes is critical for patient safety.","specificNumbers":"","methodology":"Target-trial emulation using TriNetX US Collaborative Network; propensity-score-matched 1:1 design; 2,903 matched pairs; intention-to-treat analysis.","limitations":"Observational study design cannot prove causation; potential residual confounding despite propensity matching; database study lacks granular clinical details."},{"rthcId":"RPEP-14958","title":"Incretin-Based Dual and Triple Agonists in Overweight or Obese Individuals: A Systematic Review and Meta-Analysis.","authors":"Chan, Zhi Hong; Omar, Abdousamad Said; Gill, Kieran; Volucke, Gabriele; Azhar, Muhammad Muneeb; Haleem, Syed Mohammad; Sia, Jian En; Rahman, Obaid Ur; Ahmad, Moaz; Shahid, Nuraan; Gardezi, Syed Anjum; Joseph, Kevin Vinod; Behary Paray, Nitish; Zulfiqar, Eeshal","year":2026,"journal":"Cardiology in review","doi":"10.1097/CRD.0000000000001209","pmid":"41711462","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Incretin-based dual and triple agonists demonstrate enhanced weight loss compared to single-receptor approaches, with the meta-analysis quantifying efficacy and safety across available RCTs.","whyItMatters":"Dual and triple agonists represent the next generation of obesity drugs. This meta-analysis provides the first comprehensive pooled evidence on whether targeting more receptors truly translates to better weight loss outcomes.","specificNumbers":"","methodology":"Systematic review and meta-analysis of RCTs from PubMed, Cochrane Library, and Google Scholar through June 2025.","limitations":"Limited number of available trials for triple agonists; heterogeneity in study designs and populations; most triple-agonist data from early-phase trials."},{"rthcId":"RPEP-14959","title":"Antimicrobial peptides act as a component of brain immunity against microbes in Alzheimer's disease.","authors":"Chandrashekar, Madhura; Velmurugan, Gowshika; Mishra, Amit; Chinnathambi, Subashchandrabose","year":2026,"journal":"Advances in protein chemistry and structural biology, 149, 395-418","doi":"10.1016/bs.apcsb.2025.10.016","pmid":"41581939","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Antimicrobial peptides, including amyloid-beta, function as components of brain innate immunity against microbial invasion, supporting the infectious/antimicrobial hypothesis of Alzheimer's disease.","whyItMatters":"If Alzheimer's involves microbial triggers, the entire treatment paradigm shifts — from just clearing amyloid plaques to addressing underlying infections and modulating antimicrobial immune responses in the brain.","specificNumbers":"","methodology":"Narrative review synthesizing evidence from clinical studies and basic research on AMPs in Alzheimer's disease pathology.","limitations":"Much evidence is correlational; causal relationships between infections and Alzheimer's remain debated; clinical trials targeting infections in AD have shown mixed results."},{"rthcId":"RPEP-14960","title":"Diabetic lumbosacral radiculoplexus neuropathy after glucagon-like peptide 1 receptor agonist use: A case series.","authors":"Chandrashekhar, Swathy; Davalos, Long; Pradhan, Richeek; Paul, Pritikanta","year":2026,"journal":"Journal of the neurological sciences, 481, 125755","doi":"10.1016/j.jns.2026.125755","pmid":"41534440","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Six patients developed DLRPN after GLP-1 RA use, with all showing substantial weight loss (35-52 lbs) and rapid HbA1c decline, suggesting rapid glycemic correction as the trigger mechanism.","whyItMatters":"As millions start GLP-1 drugs, clinicians need to recognize that rapid blood sugar improvements — usually celebrated — can paradoxically cause serious nerve damage in some patients.","specificNumbers":"","methodology":"Retrospective case series of 6 patients with DLRPN onset following GLP-1 receptor agonist exposure.","limitations":"Very small case series (n=6); no control group; cannot prove causation vs. coincidence; DLRPN can occur with any rapid glycemic improvement."},{"rthcId":"RPEP-14961","title":"Association of sodium-glucose cotransporter 2 inhibitors with the risk of incident anxiety and insomnia: a retrospective cohort study using the TriNetX database.","authors":"Chang, Chen-I; Lin, Jun-Fu; Chen, I-Chieh; Lin, Ching-Heng; Chen, Hsin-Hua; Chang, Ming-Hong; Tang, Chien-Lun; Pai, Yen-Wei","year":2026,"journal":"Diabetes & metabolic syndrome, 20(1), 103373","doi":"10.1016/j.dsx.2025.103373","pmid":"41477924","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The study compared incident anxiety and insomnia rates between SGLT2 inhibitor users and other antihyperglycemic agent users in type 2 diabetes, providing comparative mental health safety data.","whyItMatters":"Diabetes patients have higher rates of anxiety and insomnia. Knowing which diabetes medications help versus worsen mental health can guide treatment choices for patients dealing with both conditions.","specificNumbers":"","methodology":"Retrospective, active-comparator, multicenter cohort study using TriNetX US Collaborative Network data.","limitations":"Retrospective observational design cannot prove causation; potential confounding despite matching; database may not capture all anxiety/insomnia diagnoses."},{"rthcId":"RPEP-14962","title":"Safety of a remote disease management program to improve sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists prescribing in type 2 diabetes with elevated cardiovascular or kidney risk.","authors":"Chang, Lee-Shing; Hassan, Shahzad; Chasse, Jacqueline; Stern, Gretchen; Gabovitch, Daniel; Zelle, David; Colling, Caitlin; Crossen, Jennifer; Aronson, Samuel J; Oates, Michael; Figueroa, Christian; Collins, Emma; Ruggiero, Ryan; Plutzky, Jorge; Gaziano, Thomas A; Cannon, Christopher P; Wexler, Deborah J; Scirica, Benjamin M; Blood, Alexander J","year":2026,"journal":"American heart journal, 296, 107359","doi":"10.1016/j.ahj.2026.107359","pmid":"41610902","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A protocol-driven remote management program for SGLT2i and GLP-1 RA prescribing in high-risk T2D patients demonstrated acceptable safety with manageable adverse events.","whyItMatters":"If proven safe, remote prescribing programs could dramatically expand access to cardiovascular and kidney-protective diabetes medications, especially in underserved areas.","specificNumbers":"","methodology":"Pragmatic randomized trial (DRIVE) evaluating safety of protocol-driven remote prescribing and titration of SGLT2i and GLP-1 RA.","limitations":"Safety-focused analysis may not fully address long-term effectiveness; remote care model may not suit all patients; protocol-driven care limits individualization."},{"rthcId":"RPEP-14963","title":"Risk of depression with GLP-1 receptor agonists use in overweight or obese adults with type 2 diabetes: A new-user, active-comparator cohort study.","authors":"Chang, Yu; Hsieh, Ming-Hong; Ju, Po-Chung; Chang, Cheng-Chen","year":2026,"journal":"Diabetes, obesity & metabolism, 28(1), 197-209","doi":"10.1111/dom.70175","pmid":"41017578","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 receptor agonist use was not associated with increased depression risk compared to SGLT2 inhibitor use in a propensity-matched cohort of overweight/obese T2D patients.","whyItMatters":"Depression concerns have been raised about GLP-1 drugs, with some regulatory agencies investigating. This large real-world study provides reassuring evidence for the millions of people taking these medications.","specificNumbers":"","methodology":"New-user, active-comparator cohort study with 1:1 propensity score matching using deidentified EHR data from January 2016 to July 2024.","limitations":"Observational study cannot prove absence of risk; EHR data may underdiagnose depression; SGLT2i comparator group may not represent true baseline risk."},{"rthcId":"RPEP-14964","title":"Glucagon-like peptide-1 receptor agonists for obesity: Growing popularity met with growing questions over safety.","authors":"Chao, Ariana M; Gilden, Adam; Wadden, Thomas A","year":2026,"journal":"PLoS medicine, 23(1), e1004871","doi":"10.1371/journal.pmed.1004871","pmid":"41533690","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The rapid expansion of GLP-1 drug use for obesity necessitates careful attention to side effects, long-term outcome data, and protection against unregulated products.","whyItMatters":"With tens of millions of people now using or wanting GLP-1 drugs, distinguishing real safety signals from media hype and ensuring patients access legitimate products is a major public health priority.","specificNumbers":"","methodology":"Editorial/commentary reviewing current evidence and concerns about GLP-1 receptor agonist safety in obesity treatment.","limitations":"Commentary/opinion piece rather than original research; does not provide new safety data."},{"rthcId":"RPEP-14965","title":"Efficacy and safety of rimegepant for the acute treatment of migraine in Black or African American adults: A post hoc pooled subgroup analysis from three randomized, placebo-controlled clinical trials.","authors":"Charleston, Larry; Armand, Cynthia E; Monteith, Teshamae S; O'Brien, Hope L; Abbott, Chandra C; Pixton, Glenn C; Fullerton, Terence","year":2026,"journal":"Headache","doi":"10.1111/head.70034","pmid":"41652666","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Rimegepant 75 mg demonstrated efficacy and safety for acute migraine treatment in Black or African American adults, addressing a critical evidence gap from clinical trial underrepresentation.","whyItMatters":"Black and African American adults have similar migraine rates as White populations but are dramatically underrepresented in clinical trials. This analysis ensures treatment evidence exists for this population.","specificNumbers":"","methodology":"Post hoc pooled subgroup analysis of three randomized, placebo-controlled clinical trials; rimegepant 75 mg vs placebo.","limitations":"Post hoc subgroup analysis has less statistical power than primary analysis; may not capture all within-group diversity; limited to US-based trial participants."},{"rthcId":"RPEP-14966","title":"Investigation of the rimegepant effect on cerebral and extracerebral arteries during migraine attacks: a longitudinal magnetic resonance angiography study.","authors":"Chaudhry, Basit Ali; Younis, Samaira; Al-Mashat, Hassan; Gozalov, Emil; Amin, Tariq Mohammad; de Koning, Patrick J H; Larsson, Henrik Bo Wiberg; Amin, Faisal Mohammad","year":2026,"journal":"Brain communications, 8(1), fcag004","doi":"10.1093/braincomms/fcag004","pmid":"41574090","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Rimegepant effectively treats migraine without constricting cerebral or extracerebral arteries, as demonstrated by longitudinal MRI angiography during spontaneous attacks.","whyItMatters":"This is the first direct proof that rimegepant doesn't constrict brain blood vessels during actual migraine attacks — critical safety evidence for the millions of migraine patients who can't use triptans due to heart disease or stroke risk.","specificNumbers":"","methodology":"Prospective, longitudinal study using magnetic resonance angiography at a single academic imaging centre to measure arterial diameter during migraine attacks.","limitations":"Single academic center; likely small sample size given the logistical challenge of capturing spontaneous migraine attacks on MRI; may not represent all migraine subtypes."},{"rthcId":"RPEP-14967","title":"Circadian Regulation of m6A RNA Methylation in Migraine: Mechanisms and Therapeutic Implications.","authors":"Chauhan, Shikha Baghel; Bhandari, Ayushi; Jain, Chirag; Singh, Indu","year":2026,"journal":"Journal of molecular neuroscience : MN, 76(1), 12","doi":"10.1007/s12031-025-02468-8","pmid":"41557243","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Circadian regulation of m6A RNA methylation may modulate neuronal excitability and pain signaling in migraine, explaining the well-known time-of-day patterns of attack onset.","whyItMatters":"Understanding why migraines strike at certain times could enable chronotherapy — timing medications or interventions to match when patients are most vulnerable.","specificNumbers":"","methodology":"Narrative review synthesizing evidence from chronobiology, neuroepigenetics, and migraine research.","limitations":"Largely theoretical framework; direct evidence linking m6A circadian regulation to migraine onset in human patients is still lacking."},{"rthcId":"RPEP-14968","title":"Investigation of the stability profile of therapeutic α-MSH analogue: Insights from liquid chromatography-high resolution mass spectrometry analysis of afamelanotide.","authors":"Chawathe, Ashwini; Sharma, Nitish","year":2026,"journal":"Journal of pharmaceutical and biomedical analysis, 272, 117362","doi":"10.1016/j.jpba.2026.117362","pmid":"41547183","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"LC-HRMS analysis identified specific degradation products and pathways for afamelanotide, providing comprehensive stability profiling for this critical orphan drug.","whyItMatters":"Peptide drugs are inherently unstable. Detailed degradation profiling ensures patients receive effective medication and helps manufacturers optimize storage and formulation.","specificNumbers":"","methodology":"Liquid chromatography-high resolution mass spectrometry (LC-HRMS) stability analysis under various stress conditions.","limitations":"Forced degradation conditions may not perfectly reflect real-world storage; single peptide studied; findings may not generalize to other α-MSH analogues."},{"rthcId":"RPEP-14969","title":"Recombinant live biotherapeutics: A new frontier in peptide drug biosynthesis and precision delivery.","authors":"Chawla, Meenal; Bhange, Omkar; Das, Bhabatosh","year":2026,"journal":"Progress in molecular biology and translational science, 220, 175-207","doi":"10.1016/bs.pmbts.2025.12.002","pmid":"41714077","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Recombinant live biotherapeutics offer a novel platform for in-body peptide drug biosynthesis and precision delivery, potentially overcoming key limitations of traditional peptide therapeutics.","whyItMatters":"Most peptide drugs require injections because they're destroyed by digestion. Bacteria engineered to produce peptides inside the body could eliminate injections and enable continuous, targeted drug delivery.","specificNumbers":"","methodology":"Review chapter covering peptide production technologies, delivery challenges, and the emerging field of engineered live biotherapeutics.","limitations":"Largely theoretical with limited clinical data; regulatory challenges for live biotherapeutics are substantial; safety concerns about engineered organisms in the body."},{"rthcId":"RPEP-14970","title":"Glucagon-like Peptide Receptor Agonists and Kidney Outcomes in the Era of Personalized Medicine: Focus on Albuminuria.","authors":"Checa-Ros, Ana; Okojie, Owahabanun Joshua; Wassouf, Jacob Gabriel; Yedean, Aida; Hsueh, Wei-Chung; Hebda, Patryk; Llobell, Esther Rodriguez; Muhmenthaler, Greta Bianca; Tran, Martin Duc-Duy; D'Marco, Luis","year":2026,"journal":"Journal of personalized medicine, 16(2)","doi":"10.3390/jpm16020097","pmid":"41745389","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1RAs reduce albuminuria through multiple mechanisms beyond glycemic control, including blood pressure reduction, weight loss, and anti-inflammatory effects, supporting their role in kidney protection for T2D patients.","whyItMatters":"Diabetic kidney disease is a leading cause of dialysis worldwide. If GLP-1 drugs can prevent or slow kidney damage by reducing albuminuria, they could save millions of patients from kidney failure.","specificNumbers":"","methodology":"Narrative review integrating clinical trial evidence and meta-analyses on GLP-1RA renoprotective effects.","limitations":"Narrative review format; albuminuria reduction doesn't always translate to hard kidney endpoints (dialysis, transplant); personalized medicine approach not yet validated prospectively."},{"rthcId":"RPEP-14971","title":"Prescribing GLPs for Obesity Treatment for Adults at a University Based Health Maintenance Organization by Race, Ethnicity, and Socioeconomic Status.","authors":"Chen, Alissa S; Brunetto, Wendy; Canavan, Maureen E; Lipska, Kasia J; Richey, Elizabeth; Wilson, Madeline S; Zarro, James; Ross, Joseph S","year":2026,"journal":"Journal of general internal medicine, 41(2), 499-505","doi":"10.1007/s11606-025-09691-4","pmid":"40588707","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Black, Hispanic, and lower-socioeconomic-status patients were less likely to receive GLP-1 prescriptions for obesity within a university-based HMO, consistent with national disparity patterns.","whyItMatters":"Obesity disproportionately affects Black, Hispanic, and lower-income populations — the very groups least likely to receive the most effective treatments. This disparity perpetuates health inequity.","specificNumbers":"","methodology":"Retrospective cohort study at a university-based staff model HMO examining GLP-1 prescribing by race, ethnicity, and socioeconomic status.","limitations":"Single-center study at a university HMO; may not generalize to other healthcare settings; did not examine patient preferences or provider decision-making reasons."},{"rthcId":"RPEP-14972","title":"Peptide Receptor Radionuclide Therapy for Recurrent Neuroendocrine Tumor Liver Metastases After Liver transplantation: A Case Series.","authors":"Chen, Chiyi; Zheng, Qiming; Zhang, Li; Guo, Qingjun; Wang, Honghai; Sun, Jisan; Xie, Yan; Jiang, Wentao","year":2026,"journal":"Transplantation proceedings","doi":"10.1016/j.transproceed.2026.02.019","pmid":"41760506","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Lu-177-DOTATATE PRRT demonstrated manageable toxicity and efficacy in 7 patients with recurrent neuroendocrine tumor liver metastases post-liver transplantation while on everolimus immunosuppression.","whyItMatters":"Patients whose neuroendocrine tumors recur after liver transplantation have extremely limited treatment options. PRRT could offer a viable salvage therapy for this vulnerable population.","specificNumbers":"","methodology":"Retrospective case series of 7 patients treated with PRRT for recurrent NETLM after liver transplantation.","limitations":"Very small case series (n=7); retrospective design; no control group; long-term outcomes limited by small numbers and follow-up duration."},{"rthcId":"RPEP-14973","title":"Effect of glucagon-like peptide-1 receptor agonists on cigarette smoking consumption in type 2 diabetes patients: study protocol of a randomized, parallel -controlled clinical trial.","authors":"Chen, Da; Li, Ziyi; Zhou, Chenxia; Li, Ruoxuan; Ji, Xinnan; Feng, Bo; Song, Jun","year":2026,"journal":"Frontiers in clinical diabetes and healthcare, 7, 1665837","doi":"10.3389/fcdhc.2026.1665837","pmid":"41704542","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"This protocol establishes a rigorous framework to test whether GLP-1RAs reduce smoking in T2DM patients, with fMRI to explore neural reward pathway mechanisms.","whyItMatters":"Smoking doubles cardiovascular risk in diabetes. If GLP-1 drugs — already prescribed for blood sugar — also reduce smoking, they could provide dual protection for millions of diabetic smokers.","specificNumbers":"","methodology":"Single-center, parallel-group randomized controlled trial protocol with functional MRI neuroimaging component.","limitations":"Protocol paper only — no results yet; single-center design; T2DM patients may not represent all smokers."},{"rthcId":"RPEP-14974","title":"Vasoactive intestinal peptide modified defect-engineered ZnOx-Au-NaBH4 nanoplatform inducing pyroptosis in fibroblast-like synoviocytes for therapy of rheumatoid arthritis.","authors":"Chen, Han; Cao, Kaiyi; Zhu, Jun; Qiu, Shang; Chao, Minghao; Su, Tianyu; Zhu, Xu; Guo, Kaijin; Gao, Fenglei; Yu, Dehong; Pan, Bin","year":2026,"journal":"International journal of biological macromolecules, 336, 149390","doi":"10.1016/j.ijbiomac.2025.149390","pmid":"41330501","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"VIP-modified defect-engineered ZnOx-Au-NaBH4 nanoparticles selectively induce pyroptosis in fibroblast-like synoviocytes, demonstrating targeted cell killing for RA therapy.","whyItMatters":"Current RA treatments suppress the entire immune system, causing infections and other side effects. This approach targets only the specific cells destroying joints, potentially offering effective treatment without broad immunosuppression.","specificNumbers":"","methodology":"Preclinical laboratory study developing and testing a VIP-modified nanoplatform for targeted FLS pyroptosis induction.","limitations":"Preclinical study only; complex nanoplatform manufacturing and scaling challenges; in vivo efficacy and safety not yet demonstrated in clinical settings."},{"rthcId":"RPEP-14975","title":"Safety analysis of gepants for migraine treatment: A pharmacovigilance study using the FDA Adverse Event Reporting System (FAERS) database.","authors":"Chen, Hui; Li, Yan","year":2026,"journal":"Headache","doi":"10.1111/head.70049","pmid":"41606448","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"FAERS database analysis identified distinct safety profiles for each of the four marketed gepants, with both expected and potentially novel adverse event signals detected.","whyItMatters":"Gepants are relatively new drugs prescribed to millions. Real-world safety data from the FDA's reporting system can detect rare side effects that clinical trials miss, protecting patients.","specificNumbers":"","methodology":"Retrospective disproportionality analysis of the FDA FAERS database examining adverse event reports for rimegepant, ubrogepant, atogepant, and zavegepant.","limitations":"FAERS data is voluntary reporting — underreporting is common; cannot determine causation; reporting biases (newer drugs may be over-reported); no denominator (total prescriptions) for incidence calculation."},{"rthcId":"RPEP-14976","title":"Recurrent Weight Gain after Weight Loss Induced by Lifestyle Intervention, Metabolic and Bariatric Surgery, or Semaglutide in Adults with Obesity: A Systematic Review of Randomized Controlled Trials.","authors":"Chen, Huixian; Guo, Xiaojing; Long, Tianxue; Li, Mingzi","year":2026,"journal":"Obesity surgery, 36(2), 792-803","doi":"10.1007/s11695-025-08415-1","pmid":"41483046","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Lifestyle interventions ranked highest for preventing recurrent weight gain; semaglutide supports sustained loss during treatment but weight regain occurs after discontinuation; bariatric surgery provides the largest initial loss.","whyItMatters":"The biggest challenge in obesity treatment isn't losing weight — it's keeping it off. This analysis directly compares the long-term weight maintenance of the three major treatment approaches.","specificNumbers":"","methodology":"Systematic review and network meta-analysis of 29 RCTs with literature search through March 2025.","limitations":"Heterogeneous trial designs and follow-up durations; lifestyle intervention intensity varies widely; semaglutide discontinuation data limited; surgical techniques differ across studies."},{"rthcId":"RPEP-14977","title":"Agent- and Dose-Specific Intestinal Obstruction Safety of GLP-1 Receptor Agonists and SGLT2 Inhibitors: A Network Meta-Analysis of Randomized Trials.","authors":"Chen, Jiann-Jy; Hsu, Chih-Wei; Hung, Chao-Ming; Suen, Mein-Woei; Wang, Hung-Yu; Yang, Wei-Chieh; Stubbs, Brendon; Chen, Yen-Wen; Chen, Tien-Yu; Lei, Wei-Te; Carvalho, Andre F; Hsu, Shih-Pin; Shiue, Yow-Ling; Zeng, Bing-Yan; Li, Cheng-Ta; Su, Kuan-Pin; Liang, Chih-Sung; Zeng, Bing-Syuan; Tseng, Ping-Tao","year":2026,"journal":"International journal of molecular sciences, 27(2)","doi":"10.3390/ijms27020608","pmid":"41596262","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Network meta-analysis identifies agent- and dose-specific intestinal obstruction risks for GLP-1 RAs and SGLT2 inhibitors, clarifying safety profiles for clinical decision-making.","whyItMatters":"Intestinal obstruction is a serious, potentially life-threatening complication. As millions take GLP-1 drugs that slow gut motility, knowing which specific drugs and doses carry risk is critical for safe prescribing.","specificNumbers":"","methodology":"Network meta-analysis of randomized controlled trials evaluating intestinal obstruction as a safety outcome across GLP-1 RA and SGLT2i agents and doses.","limitations":"Intestinal obstruction is rare, limiting statistical power even in meta-analysis; RCTs may exclude patients at highest risk; event adjudication varies across trials."},{"rthcId":"RPEP-14978","title":"Prospecting of Novel Angiotensin I-Converting Enzyme Inhibitory Peptides from Bone Collagen of Pelodiscus sinensis by Computer-Aided Screening, Molecular Docking, and Network Pharmacology.","authors":"Chen, Jiaxin; Xie, Ruoyu; Mei, Yimeng; Chen, Wenxuan; Hu, Jun; Liu, Haoyu; Du, Hongying; Hao, Guijie; Ji, Xiaolong; Li, Shuangxi; Zhang, Jin","year":2026,"journal":"Foods (Basel, Switzerland), 15(4)","doi":"10.3390/foods15040663","pmid":"41750855","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Novel ACE-inhibitory peptides were identified from Pelodiscus sinensis bone collagen through computational screening and molecular docking, showing potential as natural antihypertensive agents.","whyItMatters":"Synthetic ACE inhibitors cause side effects like chronic cough in many patients. Food-derived peptides that target the same enzyme could provide blood pressure control with better tolerability.","specificNumbers":"","methodology":"Computer-aided screening, molecular docking simulation, and network pharmacology analysis of softshell turtle bone collagen peptides.","limitations":"Entirely computational — no in vitro or in vivo validation of ACE inhibition; molecular docking predictions don't always translate to real biological activity."},{"rthcId":"RPEP-14979","title":"A potent novel small molecule GLP-1R agonist identified by rational design and CADD.","authors":"Chen, Jiayu; Yao, Yuanshan; Li, Hao","year":2026,"journal":"Bioorganic & medicinal chemistry, 136, 118578","doi":"10.1016/j.bmc.2026.118578","pmid":"41650553","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Compound 6, designed through rational CADD approaches, showed a unique GLP-1R binding mode and robust efficacy in both in vitro and in vivo models as a small molecule agonist.","whyItMatters":"Most GLP-1 drugs require weekly injections that many patients resist. A potent oral pill with the same benefits would dramatically expand treatment access and adherence for diabetes and obesity.","specificNumbers":"","methodology":"Rational drug design with computer-aided drug design (CADD); in vitro receptor binding and activation assays; in vivo animal efficacy studies.","limitations":"Preclinical data only — human trials needed; oral bioavailability and safety profile require further optimization; small molecule may have different side effect profile than peptide-based drugs."},{"rthcId":"RPEP-14980","title":"Neural Circuits between Nodose Ganglion and Pulmonary Neuroendocrine Cells Regulate Lung Inflammatory Responses.","authors":"Chen, Jie; Xie, Shitao; Lin, Zhekai; Zhao, Caiqi; Tao, Rujia; Ma, Yingying; Chen, Xiaoyan; Wu, Renlan; Han, Qingjian; Sui, Pengfei; Wang, Sheng; Ji, Hongbin; Song, Hai; Zhang, Xiaoming; Sun, Yangang; Song, Yuanlin; Su, Xiao","year":2026,"journal":"Advanced science (Weinheim, Baden-Wurttemberg, Germany), 13(12), e07512","doi":"10.1002/advs.202507512","pmid":"41610307","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Vagal sensory neurons synapse with PNECs and detect endotoxins via TRPA1, forming a neural circuit that regulates lung inflammatory responses — a previously unknown brain-lung immune axis.","whyItMatters":"Understanding how the nervous system controls lung inflammation could lead to new treatments for asthma, pneumonia, and other respiratory diseases by targeting neural pathways instead of just immune cells.","specificNumbers":"","methodology":"Multi-technique study using transcriptomics, tissue clearance imaging, electrophysiology, and cell-specific knockout models in mice.","limitations":"Mouse model — human neural circuits may differ; focused on bacterial endotoxins, may not apply to all pathogens; therapeutic manipulation of this circuit not yet demonstrated."},{"rthcId":"RPEP-14981","title":"Peptide Hydrogel Incorporating Hydroxyapatite and Neural Stem Cells to Facilitate Spinal Cord Injury Regeneration.","authors":"Chen, Jing; Zhou, Haihua; Wang, Peng; Yang, Minyan","year":2026,"journal":"Current pharmaceutical biotechnology","doi":"10.2174/0113892010426601251127051435","pmid":"41735216","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The IGL-Gel/HAp/NSC composite scaffold promoted neural stem cell survival, differentiation, and spinal cord tissue regeneration in SCI treatment.","whyItMatters":"Spinal cord injuries are currently irreversible. This bioengineered scaffold approach combines structural support with biological signals to create an environment where nerve regrowth can actually occur.","specificNumbers":"","methodology":"Preclinical study involving hydrothermal synthesis of HAp nanorods, peptide hydrogel formulation, NSC incorporation, and testing in spinal cord injury models.","limitations":"Preclinical study — functional recovery in humans would be far more complex; long-term stability and integration of the scaffold unknown; stem cell survival rates in human SCI may differ."},{"rthcId":"RPEP-14982","title":"The m6A methyltransferase METTL3 regulates antimicrobial peptide expression via the Toll pathway in Eriocheir sinensis.","authors":"Chen, Jinming; Li, Yang; Hao, Qingding; Xu, Chaohui; Sheng, Guoqin; Zhou, Kaimin; Li, Weiwei; Wang, Qun; Zhu, Youting","year":2026,"journal":"Fish & shellfish immunology, 169, 111090","doi":"10.1016/j.fsi.2025.111090","pmid":"41453627","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"EsMETTL3 catalyzes m6A RNA methylation that regulates antimicrobial peptide expression through the Toll signaling pathway in Chinese mitten crabs.","whyItMatters":"Understanding how ancient immune regulation works in crustaceans helps reveal fundamental immune mechanisms conserved across species, potentially informing both aquaculture disease management and human immunology.","specificNumbers":"","methodology":"Gene identification, molecular characterization, RNA methylation analysis, and immune pathway studies in Eriocheir sinensis.","limitations":"Single crustacean species studied; in vitro and in vivo validation in other crustaceans needed; direct application to human biology requires further study."},{"rthcId":"RPEP-14983","title":"Involvement of substance P/NK1 receptor system in central sensitization in chronic pain.","authors":"Chen, Juan; Lai, Yimin; Li, Wei","year":2026,"journal":"Neuroscience letters, 871, 138464","doi":"10.1016/j.neulet.2025.138464","pmid":"41285348","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The substance P/NK1R system is involved in central sensitization in chronic pain, as demonstrated in a spared nerve injury mouse model.","whyItMatters":"Despite decades of research, effective treatments for chronic pain remain elusive. Clarifying substance P's role in central sensitization could revive interest in NK1R antagonists or related drug targets.","specificNumbers":"","methodology":"Preclinical study using spared nerve injury (SNI) mouse model with behavioral, molecular, and pharmacological analysis of substance P/NK1R system.","limitations":"Mouse model may not fully replicate human chronic pain; SNI represents neuropathic pain specifically; NK1R antagonists have previously failed in human pain trials."},{"rthcId":"RPEP-14984","title":"GLP-1 Receptor Agonist Therapy and Cardiorenal Outcomes in Patients ≥ 80 Years Old With Type 2 Diabetes.","authors":"Chen, Jui-Cheng; Fang, Yu-Wei; Liu, Ya-Fang; Chen, Mon-Ting; Tsai, Ming-Hsien","year":2026,"journal":"Journal of the American Geriatrics Society, 74(1), 96-106","doi":"10.1111/jgs.70187","pmid":"41132144","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RAs demonstrated cardiorenal benefits over DPP4 inhibitors in patients aged ≥80 with T2DM, extending the evidence base to the very elderly population.","whyItMatters":"Elderly patients are typically excluded from clinical trials, leaving doctors guessing about drug benefits in the oldest patients. This massive study provides evidence that GLP-1 drugs work for octogenarians too.","specificNumbers":"","methodology":"Retrospective comparative effectiveness study using TriNetX US database with 284,417 patients; GLP-1 RA vs DPP4i comparison.","limitations":"Retrospective database study cannot prove causation; elderly patients on GLP-1 drugs may differ from DPP4i users in unmeasured ways; tolerability and side effects in the very elderly need consideration."},{"rthcId":"RPEP-14985","title":"Glucagon-like peptide-1 receptor agonists and the risk of nonarteritic anterior ischemic optic neuropathy: Evidence from a global real-world cohort.","authors":"Chen, Jun-Wei; Yu, Frederick Tzu-En; Chen, Hsin-An; Huang, Tzu-Fu; Chen, Harn-Shen; Wu, Tzu-En","year":2026,"journal":"Diabetes & metabolism, 52(2), 101740","doi":"10.1016/j.diabet.2026.101740","pmid":"41687959","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The study evaluated NAION risk in GLP-1 RA users compared to other antidiabetic drug users and SGLT2i users specifically in a large real-world T2DM population.","whyItMatters":"NAION causes sudden, often permanent vision loss. With tens of millions taking GLP-1 drugs, even a small increased risk would affect thousands of patients.","specificNumbers":"","methodology":"Retrospective cohort study using TriNetX US Collaborative Network 2015-2024; adults with T2DM; GLP-1 RA vs other antidiabetic drugs and vs SGLT2i.","limitations":"Retrospective observational design; NAION diagnosis in databases may be inconsistent; potential confounding by indication; NAION is rare, limiting statistical precision."},{"rthcId":"RPEP-14986","title":"Does semaglutide increase the risk of non-arteritic anterior ischemic optic neuropathy? A systematic review and meta-analysis of emerging evidence.","authors":"Chen, Kai-Yang; Chan, Hoi-Chun; Chan, Chi-Ming","year":2026,"journal":"Asia-Pacific journal of ophthalmology (Philadelphia, Pa.), 15(1), 100245","doi":"10.1016/j.apjo.2025.100245","pmid":"40962119","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The systematic review and meta-analysis critically assessed the semaglutide-NAION association, synthesizing all available evidence to quantify the risk.","whyItMatters":"Semaglutide is one of the most prescribed drugs worldwide. Clear evidence about NAION risk is essential for informed prescribing and patient counseling.","specificNumbers":"","methodology":"Systematic review and meta-analysis with comprehensive literature search for studies examining semaglutide and NAION.","limitations":"Limited by the quality and quantity of available primary studies; NAION is very rare making statistical detection difficult; publication bias possible."},{"rthcId":"RPEP-14987","title":"Depression, cognition, and GLP-1 receptors: Heterogeneity and therapeutic prospects.","authors":"Chen, Mu-Hong; Bai, Ya-Mei; Tsai, Shih-Jen","year":2026,"journal":"Med (New York, N.Y.), 7(1), 100954","doi":"10.1016/j.medj.2025.100954","pmid":"41519115","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide improved attention and memory in depressed patients without significantly improving depressive symptoms, suggesting separate cognitive and mood pathways.","whyItMatters":"Cognitive deficits are among the most disabling and undertreated aspects of depression. If GLP-1 drugs can address these deficits through anti-inflammatory mechanisms, they could fill a major treatment gap.","specificNumbers":"","methodology":"Commentary on a placebo-controlled trial by Badulescu et al. examining semaglutide effects on cognition and depression.","limitations":"Brief commentary without independent data analysis. The referenced trial sample size and duration are not detailed in this piece."},{"rthcId":"RPEP-14988","title":"Effects of semaglutide on vessel morphology: Studies on the chicken chorioallantoic membrane.","authors":"Chen, Pei-Hsuan; Abood, Samar; Bloom, Steven","year":2026,"journal":"Microvascular research, 163, 104880","doi":"10.1016/j.mvr.2025.104880","pmid":"41125168","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide affected vessel morphology in the chicken CAM model, providing experimental evidence that may relate to reported ocular and reproductive safety signals.","whyItMatters":"If semaglutide affects blood vessel formation, it could explain emerging reports of eye problems (NAION) and reproductive concerns in patients, prompting more careful safety evaluation.","specificNumbers":"","methodology":"Preclinical study using chicken chorioallantoic membrane (CAM) assay to evaluate semaglutide effects on vessel development and morphology.","limitations":"Chicken embryo model may not reflect adult human vascular biology; CAM assay is a screening tool, not definitive proof of clinical risk; dose-response relationship to human dosing unclear."},{"rthcId":"RPEP-14989","title":"A coral-derived neuropeptide suppresses pentylenetetrazol (PTZ)-induced epileptic seizures and improves recognition memory deficits by modulating NPY-Y1R.","authors":"Chen, Qian; Deng, Congshuang; Huang, Xiaoshan; Wang, Aili; Xu, Nan; Cao, Kaixun; Yang, Min; Li, Shang; Lu, Qiumin; Gong, Guiyi; Lee, Simon Ming-Yuen","year":2026,"journal":"Archives of toxicology, 100(1), 321-339","doi":"10.1007/s00204-025-04164-3","pmid":"41006718","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A Scleractinia-derived neuropeptide suppressed PTZ-induced seizures and improved recognition memory by modulating NPY-Y1R signaling in mice.","whyItMatters":"Drug-resistant epilepsy affects millions worldwide. A marine-derived peptide targeting NPY receptors represents a completely new drug class for seizures that could help treatment-resistant patients.","specificNumbers":"","methodology":"Preclinical study using pentylenetetrazol (PTZ)-induced seizure mouse model with behavioral testing, pharmacological analysis, and NPY-Y1R pathway characterization.","limitations":"Mouse model of chemically induced seizures may not reflect human epilepsy; single seizure model tested; drug-resistance mechanisms in human epilepsy are diverse."},{"rthcId":"RPEP-14990","title":"A Clinical Comprehensive Evaluation of Long-Acting GLP-1 Receptor Agonists in Type 2 Diabetes Management.","authors":"Chen, Qiying; Chen, Tianyu; Lin, Weicheng; Chen, Xi","year":2026,"journal":"Diabetes, metabolic syndrome and obesity : targets and therapy, 19, 585436","doi":"10.2147/DMSO.S585436","pmid":"41710707","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A structured multi-dimensional comparison of five long-acting GLP-1RAs in China provides evidence-based rankings for clinical preference and institutional formulary decisions.","whyItMatters":"With multiple GLP-1 options available, clinicians need objective comparisons to make the best prescribing decisions. This is especially important in China where healthcare resource allocation is centralized.","specificNumbers":"","methodology":"Structured drug evaluation following Chinese medical institution guidelines; multi-dimensional clinical assessment framework.","limitations":"Evaluation framework is specific to Chinese healthcare context; may not include the newest GLP-1 drugs; subjective weighting of evaluation dimensions."},{"rthcId":"RPEP-14991","title":"AI-assisted discovery of dual antioxidant and ACE-inhibitory peptides from Hericium erinaceus.","authors":"Chen, Rongheng; Yu, Jiahao; Feng, Simin; Shao, Ping","year":2026,"journal":"Food chemistry, 506, 148179","doi":"10.1016/j.foodchem.2026.148179","pmid":"41619665","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"AI-assisted annotation identified 7 dual-function peptides in Hericium erinaceus with confirmed antioxidant and ACE-inhibitory activities through laboratory validation.","whyItMatters":"Traditional peptide discovery is slow and expensive. Using AI to predict which peptides have therapeutic properties dramatically accelerates finding natural compounds for blood pressure and oxidative stress management.","specificNumbers":"","methodology":"LLM-assisted peptide annotation (DeepSeek platform) combined with LC-MS/MS, antioxidant assays, ACE-inhibitory assays, and cellular evaluations.","limitations":"In vitro validation only — in vivo blood pressure effects not tested; peptide bioavailability and digestive stability unknown; AI predictions require experimental confirmation."},{"rthcId":"RPEP-14992","title":"Stripping cell-free DNA from its immune complex is essential for inflammation control using DNase I.","authors":"Chen, Shi; Du, Yibo; Zhu, Chenxu; Li, Chuang; Liu, Xingliang; Liu, Lixin; Chen, Yongming","year":2026,"journal":"Biomaterials, 329, 123992","doi":"10.1016/j.biomaterials.2026.123992","pmid":"41520541","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"cfDNA-LL37 immune complexes resist DNase degradation and amplify inflammation; disrupting these complexes before DNase treatment is required for effective inflammation control.","whyItMatters":"DNase therapy has shown promise for autoimmune diseases but often fails in practice. Understanding that LL37-DNA complexes block its action reveals why — and how to make it work.","specificNumbers":"","methodology":"Laboratory study examining cfDNA-LL37 immune complex formation, DNase resistance mechanisms, and strategies to improve DNase therapeutic efficacy.","limitations":"In vitro study — in vivo complex disruption strategies need validation; multiple antimicrobial peptides beyond LL37 may form similar complexes."},{"rthcId":"RPEP-14993","title":"Spatially diffuse cAMP signalling with oppositely biased GLP-1 receptor agonists in β-cells despite differences in receptor localisation.","authors":"Chen, Shiqian; Lobato, Carolina B; Wong, Carissa; Manchanda, Yusman; Viloria, Katrina; Davies, Iona; Andersen, Daniel B; Ast, Julia; Sloop, Kyle W; Hodson, David J; Broichhagen, Johannes; Bloom, Steve; Holst, Jens J; Tan, Tricia; Tomas, Alejandra; Jones, Ben","year":2026,"journal":"Molecular metabolism, 103, 102304","doi":"10.1016/j.molmet.2025.102304","pmid":"41391570","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Biased and unbiased GLP-1R agonists produce spatially diffuse cAMP signaling in beta cells despite differences in receptor internalization and localization, challenging location-dependent signaling theories.","whyItMatters":"Understanding how GLP-1 drugs actually signal inside cells is crucial for designing better drugs. If location doesn't matter for cAMP, the mechanism behind biased agonism differences must lie elsewhere.","specificNumbers":"","methodology":"Cell biology study using imaging of cAMP signaling dynamics in beta cells with oppositely biased GLP-1R agonists and receptor localization tracking.","limitations":"In vitro beta cell study; cAMP is one of several signaling pathways; other downstream effects may still be location-dependent; cell line behavior may differ from primary cells."},{"rthcId":"RPEP-14994","title":"Stapled peptide inhibitors target VGLL4/TEAD4 interactions to accelerate cutaneous wound healing.","authors":"Chen, Shuai; Gai, Conghao; Wang, Guangyao; Dong, Peng; Zhuo, Xiaobin; Zhang, Wenwen; Zhang, Pei-Chao; Chai, Xiaoyun; Xue, Hongjuan; Su, Juan; Zhao, Qingjie; Zou, Yan","year":2026,"journal":"European journal of medicinal chemistry, 304, 118508","doi":"10.1016/j.ejmech.2025.118508","pmid":"41478010","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Stapled peptide inhibitors of VGLL4-TEAD4 interactions accelerated cutaneous wound healing by activating fibroblast proliferation through the Hippo pathway.","whyItMatters":"Chronic wounds affect millions of people, especially diabetics and the elderly. A peptide that directly activates the body's tissue repair machinery could provide a targeted wound healing therapeutic.","specificNumbers":"","methodology":"Peptide design and synthesis with stapling modification; protein-protein interaction studies; wound healing assays in cell and tissue models.","limitations":"Preclinical study — human wound healing is more complex than models; peptide delivery to wound sites needs optimization; potential oncogenic concerns with growth pathway activation."},{"rthcId":"RPEP-14995","title":"Molecular Mimicry at the Gut-Immune Interface: A Mechanistic Link to Type 1 Diabetes.","authors":"Chen, Sihan; Luo, Yixin; Wei, Gaoyang; Liu, Shuiping","year":2026,"journal":"Immunology, 177(4), 701-712","doi":"10.1111/imm.70091","pmid":"41461600","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Gut microbiota dysbiosis contributes to T1D through metabolic disruption of gut barrier integrity and molecular mimicry where microbial peptides trigger cross-reactive autoimmune responses against beta cells.","whyItMatters":"T1D incidence is rising faster than genetics can explain. If gut bacteria trigger autoimmunity through molecular mimicry, it opens doors to prevention through microbiome interventions in at-risk children.","specificNumbers":"","methodology":"Comprehensive review synthesizing human clinical data, multi-omics studies, and experimental evidence on the gut microbiota-T1D connection.","limitations":"Much evidence is correlational; causal proof of molecular mimicry triggering T1D in humans is still incomplete; microbiome composition varies widely across populations."},{"rthcId":"RPEP-14996","title":"Identification of antimicrobial peptides from ancient gut microbiomes.","authors":"Chen, Sizhe; Yuan, Yue; Wang, Yun; Peng, Ye; Tun, Hein Min; Jiang, Zhimin; Miao, Yinglei; Lee, Sunjae; Yin, Xiaole; Shen, Xiaotao; DeLeon, Orlando; Chang, Eugene B; Chan, Francis Ka Leung; Sun, Yang; Ng, Siew Chien; Su, Qi","year":2026,"journal":"Nature communications, 17(1), 1788","doi":"10.1038/s41467-026-68495-0","pmid":"41535683","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"AMPLiT identified antimicrobial peptides from ancient human coprolite metagenomes with high accuracy (AUPRC 0.9486), revealing potentially extinct but efficacious AMPs.","whyItMatters":"Antibiotic resistance is a global crisis. Ancient microbiomes may harbor antimicrobial peptides that evolution refined over millennia but that modern humans have lost — a completely novel source of new antibiotics.","specificNumbers":"","methodology":"Development of AMPLiT (AMP Lightweight Identification Tool) for metagenomic AMP screening; analysis of 7 ancient human coprolite metagenomes.","limitations":"Ancient DNA is degraded and incomplete; computational predictions need experimental validation; ancient AMPs may not work against modern resistant pathogens; coprolite samples are scarce."},{"rthcId":"RPEP-14997","title":"Comparative effectiveness of pharmacotherapy for heart failure with preserved ejection fraction: A systematic review and network meta-analysis.","authors":"Chen, Szu-Han; Tseng, Yu-Wen; Huang, Chi-Jung; Yang, Shu-Mei; Fudim, Marat; Chuang, Shao-Yuan; Sung, Shih-Hsien; Cheng, Hao-Min","year":2026,"journal":"Diabetes, obesity & metabolism","doi":"10.1111/dom.70503","pmid":"41588709","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Network meta-analysis comparing HFpEF therapies suggests adiposity-targeting approaches are central to treatment, with emerging metabolic therapies showing comparative effectiveness.","whyItMatters":"HFpEF affects half of all heart failure patients but has had no definitive treatment until recently. This analysis helps rank the growing number of options for the first time.","specificNumbers":"","methodology":"Systematic review and network meta-analysis of RCTs from PubMed, Embase, and Cochrane Library through April 2025.","limitations":"HFpEF is heterogeneous; network meta-analysis assumptions may not hold across all phenotypes; limited long-term outcome data for newer therapies."},{"rthcId":"RPEP-14998","title":"Bitter gustatory receptor modulates the immune response of Coptotermes formosanus against Metarhizium anisopliae.","authors":"Chen, Weiwen; Zhang, Shijun; Li, Zhiqiang","year":2026,"journal":"Pesticide biochemistry and physiology, 218, 106940","doi":"10.1016/j.pestbp.2026.106940","pmid":"41629009","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Bitter gustatory receptors in Coptotermes formosanus modulate immune responses against M. anisopliae, revealing a novel taste-immunity axis in termite defense.","whyItMatters":"Chemical insecticides are environmentally damaging. Understanding how termites detect and fight biological control agents could improve eco-friendly pest management strategies.","specificNumbers":"","methodology":"Laboratory study examining gustatory receptor expression, immune gene modulation, and antifungal responses in termites exposed to M. anisopliae.","limitations":"Single termite and fungal species studied; mechanism may not generalize to all termite-pathogen interactions; laboratory conditions may not reflect field efficacy."},{"rthcId":"RPEP-14999","title":"Self-assembled charge-complementary hydrogel with sustained release of antimicrobial peptides for periodontitis treatment.","authors":"Chen, Wener; Zhan, Chaoning; Zhang, Chengfei; Aparicio, Conrado; Peng, Simin; Ye, Zhou; Lin, Yifan","year":2026,"journal":"Acta biomaterialia, 212, 251-265","doi":"10.1016/j.actbio.2026.01.025","pmid":"41544915","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"PA/GL13K self-assembled hydrogel achieves sustained antimicrobial peptide release in periodontal pockets through charge-complementary interactions, effectively treating periodontitis.","whyItMatters":"Periodontitis affects nearly half of adults over 30 and can lead to tooth loss and systemic health problems. A sustained-release antimicrobial hydrogel could provide effective local treatment without antibiotics.","specificNumbers":"","methodology":"Biomaterials development study combining peptide amphiphile with GL13K antimicrobial peptide; characterization of self-assembly, release kinetics, and antimicrobial efficacy.","limitations":"Preclinical study — clinical performance in human periodontal pockets may differ; long-term biocompatibility needs assessment; manufacturing scalability unknown."},{"rthcId":"RPEP-15000","title":"Impact of Short-Term Insulin Pump Therapy on Cardiometabolic Index in Patients With Newly Diagnosed Type 2 Diabetes Mellitus.","authors":"Chen, Xia; Li, Shuya; Chen, Zeren; Wang, Dong; Yang, Ling; Deng, Xia; Li, Haoxiang","year":2026,"journal":"Endocrinology, diabetes & metabolism, 9(2), e70192","doi":"10.1002/edm2.70192","pmid":"41787747","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Short-term CSII intensive therapy improved cardiometabolic index levels in newly diagnosed T2DM patients, with CMI changes correlating with insulin resistance reduction.","whyItMatters":"Early intensive insulin therapy may not just control blood sugar but also reduce cardiovascular risk markers from the very start of diabetes management.","specificNumbers":"","methodology":"Retrospective study of 604 newly diagnosed T2DM patients treated with short-term CSII; pre- and post-treatment CMI and insulin resistance assessment.","limitations":"Retrospective design; no control group for comparison; short-term outcomes only; CMI is a surrogate marker, not a hard cardiovascular endpoint."},{"rthcId":"RPEP-15001","title":"Viral glycoprotein-mimicking peptide-functionalized micelles promote drug delivery to diseased chondrocytes for osteoarthritis alleviation.","authors":"Chen, Xiao; Zhou, Dongyang; Wang, Jian; Liu, Han; Zhang, Hao; Geng, Zhen; Wang, Guangchao; Shen, Hao; Zhang, Yuanwei; Li, Zuhao; Wang, Dongliang; Ren, Xiaoxiang; Wang, Xiuhui; Xu, Ke; He, Chongru; Bai, Long; Wei, Yan; Chen, Xiaoyuan; Su, Jiacan","year":2026,"journal":"Nature nanotechnology, 21(2), 300-310","doi":"10.1038/s41565-025-02082-0","pmid":"41461939","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CMP-functionalized micelles successfully deliver drugs to diseased chondrocytes using a dual-targeting approach: collagen adhesion and MMP-13-activated cell penetration.","whyItMatters":"Most osteoarthritis drugs fail because they can't reach cartilage cells. This targeted delivery system could make disease-modifying OA treatments finally viable.","specificNumbers":"","methodology":"Peptide design and synthesis; micelle formulation; in vitro and in vivo drug delivery studies in osteoarthritis models.","limitations":"Preclinical study; joint injection may still be required; long-term cartilage effects and safety need evaluation; manufacturing complexity of peptide-micelle system."},{"rthcId":"RPEP-15002","title":"A Melittin-Derived Lead Compound Ameliorates Severe Acute Pancreatitis by Restoring Oxidative Homeostasis and Macrophage Metabolism.","authors":"Chen, Xiaolong; Chen, Ya; Mao, Yunyun; Chen, Xinxin; Zhou, Yilin; Tu, Jianfeng","year":2026,"journal":"Inflammation, 49(1), 59","doi":"10.1007/s10753-025-02444-9","pmid":"41569335","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"HMLT, a histidine-substituted melittin derivative, ameliorates SAP by restoring oxidative homeostasis and macrophage metabolism with significantly reduced cytotoxicity versus native melittin.","whyItMatters":"Severe acute pancreatitis kills 20-30% of patients and has no specific treatment. A detoxified version of a potent natural anti-inflammatory peptide could become the first targeted therapy.","specificNumbers":"","methodology":"Peptide design with histidine substitutions; cytotoxicity comparison; SAP models evaluating oxidative stress, macrophage metabolism, and anti-inflammatory efficacy.","limitations":"Preclinical study; SAP models may not fully replicate human disease complexity; optimal dosing and route for human use not established."},{"rthcId":"RPEP-15003","title":"Semaglutide Inhibits Neuronal Apoptosis and Improves Cognitive Function in Mice after Traumatic Brain Injury, Mainly via the Caspase-Dependent Pathway.","authors":"Chen, Xiyu; Zhang, Bin; Yang, Mengshi; Zhuang, Yuan; Liao, Xixian; Shi, Guangzhi","year":2026,"journal":"Neurocritical care","doi":"10.1007/s12028-025-02446-3","pmid":"41644924","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide provided neuroprotection after TBI by inhibiting caspase-dependent neuronal apoptosis, resulting in improved cognitive function in mouse models.","whyItMatters":"TBI affects millions worldwide with no approved neuroprotective treatment. Repurposing an already-approved drug like semaglutide for brain injury could fast-track clinical trials.","specificNumbers":"","methodology":"Preclinical mouse TBI model with semaglutide treatment; cognitive behavioral testing; molecular analysis of caspase-dependent apoptosis pathways.","limitations":"Mouse TBI model may not replicate human brain injury; single time point and dose may miss optimal treatment windows; TBI severity and type vary widely in humans."},{"rthcId":"RPEP-15004","title":"Optimization of 68Ga-DOTA radiolabeling conditions for disulfide-directed multicyclic peptides and amphiphilic antimicrobial peptides.","authors":"Chen, Xueyao; Zhang, Siqi; Jiang, Shuo; Hu, Kuan","year":2026,"journal":"Bioorganic & medicinal chemistry letters, 130616","doi":"10.1016/j.bmcl.2026.130616","pmid":"41786055","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Optimized 68Ga-DOTA radiolabeling conditions were established for DDMPs and AAMPs, overcoming challenges that prevented standard protocols from achieving adequate labeling efficiency.","whyItMatters":"PET imaging with peptide tracers can detect cancers, infections, and other diseases. Enabling radiolabeling of more complex peptide structures expands the diagnostic toolkit.","specificNumbers":"","methodology":"Radiochemistry optimization study varying temperature, pH, time, buffer, and other conditions for 68Ga-DOTA labeling of complex peptides.","limitations":"Optimization in laboratory conditions; clinical imaging performance of these specific tracers needs validation; Ga-68 short half-life limits imaging windows."},{"rthcId":"RPEP-15005","title":"Cascade Therapy of Periodontitis via Sequential Release of Ribosome-Targeting Antimicrobial Peptide and Irisin From a Multifunctional MOF-Based System.","authors":"Chen, Yan; Xu, Zheng; Xue, Yunmo; Liu, Shanshan; Zhang, Xiang; Guo, Jingyao; Yao, Minhui; Liu, Yue; Lu, Xiaolin; Qian, Jieshu; Ma, Qian","year":2026,"journal":"Advanced science (Weinheim, Baden-Wurttemberg, Germany), e21553","doi":"10.1002/advs.202521553","pmid":"41589569","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Sequential release of ribosome-targeting AMP followed by irisin from a MOF-based system addresses infection, inflammation, and bone loss in periodontitis comprehensively.","whyItMatters":"Periodontitis destroys jaw bone and current treatments can't rebuild it. This cascade approach — kill bacteria first, then rebuild bone — addresses the full disease cycle for the first time.","specificNumbers":"","methodology":"Multifunctional MOF system design with sequential drug release; antimicrobial testing; anti-inflammatory evaluation; bone regeneration assessment.","limitations":"Preclinical study; MOF biocompatibility in oral environment needs long-term assessment; manufacturing complexity; optimal release timing for human periodontitis unknown."},{"rthcId":"RPEP-15006","title":"A Radiotherapy-Responsive Peptide Hydrogel for Pulsatile Release of mRNA-LNPs Synergizes with Immune Activation to Prevent Breast Cancer Recurrence.","authors":"Chen, Yanbin; Cai, Xiaoyao; Lan, Dingxuan; Zou, Lanbing; Lyu, Chaoyi; Mu, Ganen; Yang, Lijun; Jia, Haixue; Liu, Jianfeng; Yang, Cuihong","year":2026,"journal":"Advanced materials (Deerfield Beach, Fla.), 38(8), e17770","doi":"10.1002/adma.202517770","pmid":"41328880","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A radiotherapy-responsive peptide hydrogel enables pulsatile release of mRNA-LNPs synchronized with radiation, synergizing with immune activation to prevent breast cancer recurrence.","whyItMatters":"Breast cancer recurrence after surgery remains a major clinical challenge. Combining radiation with timed mRNA vaccine delivery could create the durable immune response needed to eliminate residual cancer cells.","specificNumbers":"","methodology":"Biomaterials design with radiation-responsive peptide hydrogel; mRNA-LNP loading and pulsatile release characterization; breast cancer recurrence prevention models.","limitations":"Preclinical study; hydrogel placement requires surgical access; mRNA vaccine neoantigen selection varies per patient; long-term immune durability not yet shown."},{"rthcId":"RPEP-15007","title":"An engineered micropatch for oral delivery of heterophyllin B in type 2 diabetes treatment.","authors":"Chen, Yi; Huang, Yuanxing; Huang, Cheneryu; Zhang, Shu; Fan, Mengyu; Yuan, Xu; Huang, Cao; Zhang, Man; Peng, Jianqing; Sun, Runbin; Zhang, Shuai; Chen, Wenzhang; Gong, Zipeng","year":2026,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 114782","doi":"10.1016/j.jconrel.2026.114782","pmid":"41786043","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Engineered micropatch enables oral delivery of heterophyllin B, a cyclic plant peptide that alleviates T2DM by modulating hepatic IRS2/PI3K-Akt/FoxO1 signaling and restoring bile acid metabolism.","whyItMatters":"Traditional medicine contains many potential diabetes drugs that can't be taken orally. Engineering delivery systems that work for cyclic peptides could unlock a whole class of natural therapeutics.","specificNumbers":"","methodology":"Preclinical study with mechanistic pathway analysis, metabolomics, and micropatch oral delivery system engineering for heterophyllin B.","limitations":"Preclinical study; micropatch technology needs scalability assessment; long-term safety in humans unknown; regulatory pathway for traditional medicine-derived peptides is complex."},{"rthcId":"RPEP-15008","title":"Effect of Glucagon-Like Peptide-1 Receptor Agonists on Cardiometabolic Risk Factors in Type 1 Diabetes Mellitus: A Systematic Review and Meta-Analysis.","authors":"Chen, Yizhu; Tang, Yufei; Yue, Rui; Yang, Bo; Wang, Ai; Long, Yang; Xu, Yong; Gao, Chenlin","year":2026,"journal":"Diabetes/metabolism research and reviews, 42(1), e70111","doi":"10.1002/dmrr.70111","pmid":"41331723","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The meta-analysis evaluated GLP-1RA adjunctive therapy effects on cardiometabolic risk factors in T1DM across available RCTs, extending evidence beyond the established T2DM indications.","whyItMatters":"Type 1 diabetes patients also face elevated cardiovascular risk. If GLP-1 drugs provide cardiometabolic benefits in T1DM, millions of additional patients could benefit.","specificNumbers":"","methodology":"Systematic review and meta-analysis of RCTs from PubMed, Embase, Cochrane Library, and Web of Science through August 2025; PRISMA methodology.","limitations":"Likely few available RCTs in T1DM; studies may be small and heterogeneous; GLP-1 drugs are not approved for T1DM; hypoglycemia risk with insulin combination."},{"rthcId":"RPEP-15009","title":"An additional mechanism of HSD3B in regulating maternal care behavior in the wolf spiders, neuropeptides.","authors":"Chen, Yunru; Xu, Tianhong; Wang, Jingting; Wang, Yuan; Yu, Na; Chen, Tao; Liu, Zewen","year":2026,"journal":"Pesticide biochemistry and physiology, 216(Pt 1), 106753","doi":"10.1016/j.pestbp.2025.106753","pmid":"41326071","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"HSD3B regulates maternal care behavior in wolf spiders through neuropeptide signaling pathways, providing an additional mechanism beyond previously known hormonal regulation.","whyItMatters":"Understanding how neuropeptides control complex social behaviors in spiders provides insights into the evolution of parental care and could improve biological pest control using these natural predators.","specificNumbers":"","methodology":"Molecular biology study identifying neuropeptides and HSD3B regulatory pathways in Pardosa pseudoannulata maternal behavior.","limitations":"Single spider species studied; causal relationship between neuropeptides and behavior needs further functional validation; laboratory behavior may differ from field conditions."},{"rthcId":"RPEP-15010","title":"Changes of chicken liver-enriched antimicrobial peptide 2 across feeding states and body weight and its regulatory role in feed intake.","authors":"Chen, Z; Liu, L; Shu, X; Wang, H; Xu, B; Zhang, J; Wang, M; Shen, M; Zheng, X; Chen, J","year":2026,"journal":"British poultry science, 67(1), 151-158","doi":"10.1080/00071668.2025.2527227","pmid":"40991231","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"LEAP2 expression varies with feeding state and body weight in broilers, and intraperitoneally injected LEAP2 modulates feed intake in chicks, confirming its role in avian appetite regulation.","whyItMatters":"Feed efficiency is the largest cost in poultry production. Understanding LEAP2's role in appetite regulation could lead to strategies for optimizing feed conversion in commercial poultry.","specificNumbers":"","methodology":"Gene expression analysis across feeding states and body weights in adult broilers; intraperitoneal injection of LEAP2 and ghrelin in chicks with feed intake measurement.","limitations":"Poultry model — direct translation to human appetite regulation uncertain; intraperitoneal injection doesn't reflect normal physiological signaling; broiler chickens may have altered metabolic regulation from selective breeding."},{"rthcId":"RPEP-15011","title":"Macrophage-targeted amphiphilic peptide nanocarrier for intracellular MRSA infection therapy.","authors":"Chen, Zaipeng; Wu, Yuling; Nie, Zhiqiang; Mao, Tengfei; Tao, Junjun; Tang, Changming; Ruan, Huajun; Lang, Xin; Zhou, Wei; Lu, Jiaju; Li, Xigong","year":2026,"journal":"Colloids and surfaces. B, Biointerfaces, 257, 115151","doi":"10.1016/j.colsurfb.2025.115151","pmid":"40987189","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"RFP@TVYV amphiphilic peptide nanocarrier achieves macrophage-targeted delivery and intracellular MRSA eradication through sequential targeting using tuftsin modification.","whyItMatters":"Intracellular MRSA infections cause treatment failures and chronic infections. Delivering antimicrobials directly inside the immune cells where bacteria hide could solve one of infectious disease's toughest challenges.","specificNumbers":"","methodology":"Peptide nanocarrier design with tuftsin modification; macrophage uptake studies; intracellular MRSA killing assays; in vitro and in vivo infection models.","limitations":"Preclinical study; macrophage-targeted delivery may vary between tissue compartments; manufacturing scalability of peptide nanocarriers; potential immunogenicity."},{"rthcId":"RPEP-15012","title":"Effects of different dietary methionine and cysteine ratios on growth performance and intestinal development of broilers from brain-gut peptide secretion perspective.","authors":"Chen, Zhihui; Zhao, Yang; Chai, Haoliang; Zhao, Dexin; Xu, Liangmei; Teng, Teng","year":2026,"journal":"Animal bioscience","doi":"10.5713/ab.250787","pmid":"41679269","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Methionine-to-cysteine dietary ratios modulate broiler growth and intestinal development through altered brain-gut peptide secretion patterns identified via proteomic analysis.","whyItMatters":"Optimizing amino acid ratios can improve poultry feed efficiency, reducing costs and environmental impact of meat production while improving animal welfare.","specificNumbers":"","methodology":"Randomized feeding trial with 216 broiler chicks in 3 dietary groups; growth performance measurement; hypothalamus and ileum proteomic analysis.","limitations":"Single broiler strain (Arbor Acres); short growth period studied; proteomic associations don't prove causation."},{"rthcId":"RPEP-15013","title":"A WR3-NH2-loaded polysaccharide hydrogel with antibacterial, anti-inflammatory, and pro-healing properties for enhanced wound healing.","authors":"Chen, Zhizhi; Li, Chao; Wang, Lei; Luo, Ying; Yang, Yahan; Han, Qinqin; Zhang, Jinyang; Shi, Yaoqiang; Sun, Yi; Song, Yuzhu","year":2026,"journal":"Materials today. Bio, 36, 102701","doi":"10.1016/j.mtbio.2025.102701","pmid":"41560842","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"SGHC-WR hydrogel with WR3-NH2 antimicrobial peptide demonstrated triple function: antibacterial activity, anti-inflammatory effects, and pro-healing tissue regeneration in wound models.","whyItMatters":"Chronic wounds cost billions in healthcare annually. A single product that fights infection, controls inflammation, and promotes healing could simplify treatment and improve outcomes.","specificNumbers":"","methodology":"Hydrogel development and characterization; in vitro antibacterial, anti-inflammatory, and wound healing studies; physicochemical property assessment.","limitations":"In vitro studies primarily; clinical wound healing involves far more complexity; hydrogel shelf stability and sterility need assessment; regulatory pathway for peptide-loaded devices."},{"rthcId":"RPEP-15014","title":"mRNA mediated expression of novel fusion phage tail protein with antimicrobial peptides inside macrophages for targeted clearance of intracellular Mycobacterium tuberculosis.","authors":"Chen, Ziwei; Fan, Xueting; Zhou, Liying; Zou, Lihui; Wan, Li; Li, Yayu; Li, Chang; Kuai, Lu; Cai, Jiahui; Zhang, Lili; Li, Yifei; Li, Hexin; Wan, Kanglin; Liu, Haican; Xu, Hongtao; Xiao, Fei","year":2026,"journal":"Emerging microbes & infections, 15(1), 2627075","doi":"10.1080/22221751.2026.2627075","pmid":"41632588","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"mRNA-mediated expression of fusion phage tail-AMP proteins inside macrophages enables targeted intracellular clearance of M. tuberculosis, overcoming the limitations of extracellular-focused anti-TB drugs.","whyItMatters":"TB kills 1.3 million people annually, and intracellular persistence drives treatment failure and recurrence. Turning macrophages into self-defending cells could revolutionize TB treatment.","specificNumbers":"","methodology":"In vitro mRNA expression platform development; fusion protein design combining phage tail protein and AMPs; intracellular Mtb killing assays in macrophages.","limitations":"In vitro platform — in vivo delivery of mRNA to lung macrophages is a major challenge; fusion protein expression levels and duration need optimization; TB treatment requires prolonged therapy."},{"rthcId":"RPEP-15015","title":"Association Between GLP-1 Receptor Agonist Use and Epilepsy Risk in Type 2 Diabetes.","authors":"Cheng, Ching-Yang; Lo, Shih-Chang; Huang, Chien-Ning; Yang, Yi-Sun; Wang, Yu-Hsun; Kornelius, Edy","year":2026,"journal":"Neurology, 106(1), e214509","doi":"10.1212/WNL.0000000000214509","pmid":"41370744","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RA use was associated with lower incident epilepsy risk compared to DPP-4i use in adults with T2DM, providing real-world evidence supporting preclinical neuroprotective findings.","whyItMatters":"Adding epilepsy prevention to GLP-1 drugs' growing list of neuroprotective benefits strengthens the case for early use in diabetic patients at risk for neurological complications.","specificNumbers":"","methodology":"Retrospective comparative effectiveness study; GLP-1 RA vs DPP-4i users with T2DM; incident epilepsy as primary outcome.","limitations":"Retrospective observational design; potential confounding by indication; epilepsy diagnosis in databases may be imprecise; association doesn't prove causation."},{"rthcId":"RPEP-15016","title":"Glucose-dependent insulinotropic polypeptide (GIP) acts as an appetite regulator rather than as a hypoglycemic incretin in grass carp.","authors":"Cheng, Danhong; Sun, Manjie; Huang, Jinqian; Luo, Shan; Chen, Haotian; Jin, Shengzhen; Zhang, Yanpeng; Yuan, Xiaochen","year":2026,"journal":"Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology, 283, 111192","doi":"10.1016/j.cbpb.2025.111192","pmid":"41482055","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GIP functions as an appetite regulator rather than a hypoglycemic incretin in grass carp, raising blood glucose and modulating feeding behavior — opposite to its mammalian role.","whyItMatters":"Understanding how incretin hormones evolved different functions across species provides insights into metabolic regulation and could improve aquaculture feeding strategies.","specificNumbers":"","methodology":"Intraperitoneal injection of synthetic grass carp GIP; 24-hour monitoring of blood glucose, hepatic gene expression (g6pase, pepck), and feeding behavior.","limitations":"Single fish species studied; acute injection may not reflect chronic physiological role; grass carp are herbivorous, which may influence incretin function."},{"rthcId":"RPEP-15017","title":"Effect of Calorie Restricted Diet Versus Liraglutide on Intrapancreatic Fat Deposition in People With Obesity: A Pilot Study.","authors":"Cheng, Haiyan; Jiang, Xiao; Zhu, Xiaowei; Zhu, Xiaowen; Li, Chenxi; Cao, Mengjiao; Zhou, Qunyan; Deng, Shukun; Wu, Wenjun","year":2026,"journal":"Obesity (Silver Spring, Md.)","doi":"10.1002/oby.70153","pmid":"41736232","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The pilot study compared changes in pancreatic fat fraction between calorie restriction and liraglutide over 24 weeks, with secondary analysis of weight, liver fat, and glycemic parameters.","whyItMatters":"Pancreatic fat is an emerging target in diabetes prevention. If GLP-1 drugs reduce pancreatic fat specifically, it could protect insulin-producing cells and prevent diabetes progression.","specificNumbers":"","methodology":"Prospective nonrandomized 24-week study; CRD vs liraglutide in obesity; primary endpoint: pancreatic fat fraction by MRI.","limitations":"Pilot study with small sample; nonrandomized design introduces bias; 24 weeks may be insufficient for maximum fat reduction; liraglutide vs newer GLP-1 drugs not compared."},{"rthcId":"RPEP-15018","title":"Inflammation-triggered self-immolative conjugates enable oral peptide delivery by overcoming gastrointestinal barriers.","authors":"Cheng, Juan; Wu, Peng; Li, Chenwen; Han, Ying; Sun, Menglong; Dou, Yin; Chen, Sheng; Zhang, Jianxiang","year":2026,"journal":"Science advances, 12(3), eaea2989","doi":"10.1126/sciadv.aea2989","pmid":"41533788","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"SIPPC platform enables oral peptide delivery through self-assembly into protective nanoparticles that are triggered to release their peptide cargo by ROS at inflammatory gut sites.","whyItMatters":"Oral peptide delivery is the holy grail of pharmaceutical science. A platform that protects peptides through digestion AND targets them to inflamed tissue could transform treatment for IBD, Crohn's disease, and other GI conditions.","specificNumbers":"","methodology":"Chemical synthesis of self-immolative conjugates; nanoparticle characterization; GI stability testing; inflammation-targeted release studies.","limitations":"Preclinical development; ROS levels vary across patients and disease states; manufacturing complexity; clinical translation requires extensive pharmacokinetic studies."},{"rthcId":"RPEP-15019","title":"Peptide-functionalized membrane camouflage for endogenous H2S-induced photothermal immunotherapy of orthotopic colorectal cancer.","authors":"Cheng, Kai; Zhang, Fang; Zou, Jia-Hua; Lei, Xiao-Ling; Xie, Xiao-Ting; Guo, Yan-Bin; Wang, Guo-Ping; Liu, Bo; Zhao, Yuan-Di; Xia, Jiang; Fan, Jin-Xuan","year":2026,"journal":"Nature communications, 17(1), 168","doi":"10.1038/s41467-025-65876-9","pmid":"41484054","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"PfCC biomimetic platform combines antimicrobial peptide-functionalized cancer cell membrane camouflage with endogenous H2S-activated photothermal immunotherapy for colorectal cancer.","whyItMatters":"Colorectal cancer has high recurrence and metastasis rates. Combining heat-based killing with immune activation using the body's own chemistry could provide durable cancer control.","specificNumbers":"","methodology":"Biomimetic nanoparticle design; cancer cell membrane coating with antimicrobial peptide functionalization; orthotopic CRC models; H2S-responsive photothermal and immune evaluation.","limitations":"Complex multi-component system; manufacturing scalability challenges; tumor H2S levels vary between patients; photothermal therapy requires light access to tumor."},{"rthcId":"RPEP-15020","title":"Puerarin Improves Glucose and Lipid Metabolism in Type 2 Diabetes by Regulating Gut Microbiota Homeostasis and Promoting Adipose Tissue Thermogenesis.","authors":"Cheng, Long; Gan, Minghong; Wang, Huiyang; Song, Yanru; Bai, Yang; Zhang, Dongfang","year":2026,"journal":"Phytotherapy research : PTR","doi":"10.1002/ptr.70254","pmid":"41696817","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Puerarin ameliorates T2D glucose and lipid metabolism through gut microbiota homeostasis restoration and adipose tissue thermogenesis promotion.","whyItMatters":"Natural compounds that improve diabetes through gut-fat axis modulation could complement or provide alternatives to pharmaceutical treatments, especially in populations using traditional medicine.","specificNumbers":"","methodology":"Preclinical T2D study examining puerarin effects on gut microbiome composition, adipose tissue thermogenesis, glucose metabolism, and lipid profiles.","limitations":"Preclinical study; puerarin bioavailability is limited orally; human clinical trials needed; dose translation from animals uncertain."},{"rthcId":"RPEP-15021","title":"A pH-Triggered antibacterial and lubricating dual-function hydrogel coating for infection-resistant urinary catheters.","authors":"Cheng, Ming; Lin, Weijie; Yu, Jianbo; Gao, Peiliang; Shi, Fange; Wang, Chunyu; Ma, Yong; Liu, Zhongdi; Dong, Guiying","year":2026,"journal":"Frontiers in bioengineering and biotechnology, 14, 1751442","doi":"10.3389/fbioe.2026.1751442","pmid":"41647355","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Bilayer PL@SAMT/Mg hydrogel coating provides pH-triggered controlled antibacterial release and sustained lubrication for infection-resistant urinary catheters.","whyItMatters":"Catheter-associated UTIs are the most common healthcare-acquired infection worldwide. A coating that fights infection on demand while improving comfort could reduce UTI rates and improve quality of care.","specificNumbers":"","methodology":"Hydrogel coating development; pH-responsive release characterization; antibacterial efficacy testing; lubrication and adhesion studies.","limitations":"Preclinical development; long-term coating stability in urine environment needs validation; clinical performance may differ from lab conditions."},{"rthcId":"RPEP-15022","title":"Beyond the antrum: troubleshooting pitfalls of gastric ultrasound.","authors":"Cheng, Peter; Perlas, Anahi; Girón-Arango, Laura","year":2026,"journal":"Regional anesthesia and pain medicine","doi":"10.1136/rapm-2025-107362","pmid":"41554629","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Increasing GLP-1 RA use has expanded gastric ultrasound utility, but 2-5% of exams yield indeterminate results that require knowledge of troubleshooting pitfalls beyond standard antral assessment.","whyItMatters":"GLP-1 drugs delay stomach emptying, increasing aspiration risk during anesthesia. Anesthesiologists need reliable gastric assessment tools, and understanding ultrasound limitations is critical for patient safety.","specificNumbers":"","methodology":"Clinical review/educational article on gastric ultrasound technique, pitfalls, and troubleshooting in the context of GLP-1 RA use.","limitations":"Educational review rather than original research; ultrasound technique is operator-dependent; GLP-1 effects on gastric emptying vary between patients."},{"rthcId":"RPEP-15023","title":"Frog-Derived Peptide RL-RF10 Facilitates Gingival Repair and Regeneration Through the Integrin αvβ3/p38/Snail1 Axis.","authors":"Cheng, Tingting; Zhou, Jianzhong; Yang, Haoran; Zhao, Anna; Chen, Yuxiang; Xianqi, Rao; Li, Jing; Li, Lin; Yang, Xinwang; Li, Ziliang","year":2026,"journal":"International dental journal, 76(1), 109337","doi":"10.1016/j.identj.2025.109337","pmid":"41443049","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"RL-RF10 promotes gingival tissue repair and regeneration through the integrin αvβ3/p38/Snail1 axis, representing the first potential specific medication for gum tissue restoration.","whyItMatters":"Gum recession affects millions and currently has no drug treatment — only surgical tissue redistribution. A peptide that actually grows new gum tissue would be groundbreaking in dentistry.","specificNumbers":"","methodology":"Preclinical study with peptide localization monitoring, gingival cell proliferation assays, and signaling pathway analysis.","limitations":"Preclinical study; clinical application in the complex oral environment needs validation; peptide stability in saliva and gingival crevicular fluid unknown."},{"rthcId":"RPEP-15024","title":"Multi-database pharmacovigilance assessment of GLP-1 receptor agonist-related ophthalmic risks using advanced signal detection in FAERS and vigibase.","authors":"Cheng, Xiao; Jiang, Ziwei; Li, Guangyao; Wang, Jiawei; Han, Furong","year":2026,"journal":"Journal of endocrinological investigation, 49(2), 425-433","doi":"10.1007/s40618-025-02712-3","pmid":"41021211","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Multi-database pharmacovigilance analysis using advanced signal detection identified and characterized ocular toxicity signals associated with GLP-1 RAs across both FAERS and VigiBase.","whyItMatters":"Tens of millions use GLP-1 drugs. Systematically detecting eye risks across the world's two largest drug safety databases provides the strongest real-world safety signal assessment possible.","specificNumbers":"","methodology":"Pharmacovigilance study using advanced signal mining across FDA FAERS and WHO VigiBase databases for GLP-1 RA ocular adverse events.","limitations":"Pharmacovigilance databases rely on voluntary reporting; cannot determine causation or true incidence; signal detection identifies associations requiring clinical confirmation."},{"rthcId":"RPEP-15025","title":"Progress of Deep Learning Prediction of CD8+ T-Cell Epitopes.","authors":"Cheng, Xiaorui; Wu, Haixia; Chen, Pengji; Liu, Rui; Lei, Yuanyuan; Mei, Hu; Wang, Pingqing","year":2026,"journal":"Proteomics, 26(1), 6-21","doi":"10.1002/pmic.70101","pmid":"41452164","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Deep learning methods increasingly outperform traditional approaches for CD8+ T-cell epitope prediction, with various architectures showing improved accuracy for identifying immune-activating peptides.","whyItMatters":"Faster, cheaper epitope prediction accelerates vaccine development and personalized cancer immunotherapy — reducing timelines from months to minutes.","specificNumbers":"","methodology":"Review of deep learning approaches including model architectures, training strategies, and performance comparisons for epitope prediction.","limitations":"Models trained on available data which may be biased toward well-studied organisms and MHC alleles; predictions still require experimental validation; rare epitopes may be poorly predicted."},{"rthcId":"RPEP-15026","title":"Clinical utility of the four-dimensional automatic left atrial quantification technique in evaluating left atrial volume and function in patients with heart failure with preserved ejection fraction.","authors":"Cheng, Yuehong; Zhang, Lijuan; Li, Lei; Fei, Mengyao; Wang, Yao; Zhang, Pingyang","year":2026,"journal":"Quantitative imaging in medicine and surgery, 16(2), 113","doi":"10.21037/qims-2025-1046","pmid":"41669420","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"4D LAQ technology effectively evaluates LA volume, function, and strain in HFpEF, with circumferential strain providing additional diagnostic value in this patient population.","whyItMatters":"HFpEF is notoriously difficult to diagnose and monitor. Better tools for measuring left atrial function could improve diagnosis, treatment monitoring, and outcome prediction.","specificNumbers":"","methodology":"Prospective clinical study with 184 suspected HFpEF patients and 68 healthy controls using 4D LAQ echocardiographic technology.","limitations":"Single-center study; 4D LAQ technology requires specialized equipment and training; optimal strain thresholds for clinical decisions need validation."},{"rthcId":"RPEP-15027","title":"Hinged amphipathic peptides with pH-inducible positive charges: A selective battering ram against bacterial outer membrane in infection sites.","authors":"Cheon, Dae Hee; Choi, Yoonhwa; Arya, Rekha; Hur, Yuna; Choe, Hyeong Woon; Nam, So Hee; Hyun, Soonsil; Chaurasia, Akhilesh Kumar; Yu, Jaehoon; Kim, Kyeong Kyu; Lee, Yan","year":2026,"journal":"Biomaterials, 328, 123891","doi":"10.1016/j.biomaterials.2025.123891","pmid":"41352311","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"KLH3 and KLH4 histidine-modified peptides show pH-dependent selective activity against gram-negative bacteria, becoming active battering rams against bacterial membranes only at acidic infection sites.","whyItMatters":"Antimicrobial peptides often harm healthy cells too. pH-triggered activation solves this by creating peptides that only work at infection sites, potentially enabling systemic antimicrobial peptide therapy.","specificNumbers":"","methodology":"Peptide design with histidine substitutions; pH-dependent activity characterization; outer membrane disruption studies; antibacterial efficacy testing.","limitations":"In vitro characterization; in vivo selectivity between infection sites and normal tissue needs demonstration; pH at different infection types varies."},{"rthcId":"RPEP-15028","title":"Strategic Approaches for Overcoming Peptide and Protein Drug Limitations.","authors":"Cheshomi, Mahsa; Shobeiri, Nikta; Tajani, Amineh Sadat; Khameneh, Bahman","year":2026,"journal":"The protein journal, 45(1), 8-21","doi":"10.1007/s10930-025-10302-8","pmid":"41206379","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Current strategies including PEGylation, lipidation, nanoformulation, and advanced delivery systems can effectively address the chemical instability, short half-life, and poor bioavailability of peptide drugs.","whyItMatters":"Peptide drugs are the fastest-growing drug class, but their limitations still restrict their potential. Understanding and overcoming these challenges is essential for the entire field.","specificNumbers":"","methodology":"Comprehensive literature review of peptide drug challenges and strategic solutions across multiple domains.","limitations":"Review format — doesn't generate new data; some strategies work for specific peptides but not universally; cost and manufacturing complexity of advanced formulations."},{"rthcId":"RPEP-15029","title":"Comparative effectiveness of continuous positive airway pressure and glucagon-like peptide-1 receptor agonists in obstructive sleep apnea: A network meta-analysis of randomised trials.","authors":"Chiappa, Gaspar R; Santos, Paula C N; Cavalcante, Deivyd Vieira Silva; Sá Filho, Alberto Souza; Prado, Natalia; Lombardo, Katia Marques; Sequero, Pedro Sanchez; Esquinas, Antonio M","year":2026,"journal":"Diabetes, obesity & metabolism","doi":"10.1111/dom.70572","pmid":"41725443","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Network meta-analysis compared CPAP, GLP-1 RAs, and combination therapy for OSA, evaluating the primary endpoint of AHI along with sleepiness and metabolic outcomes.","whyItMatters":"Millions with OSA struggle with CPAP adherence. If GLP-1 drugs provide comparable or complementary benefits, patients could have alternatives or combination options for better sleep apnea management.","specificNumbers":"","methodology":"Network meta-analysis of randomized trials from PubMed, Embase, and CENTRAL through August 2025; comparing CPAP, GLP-1 RAs, combination, and no treatment.","limitations":"Limited number of GLP-1 RA trials specifically in OSA; indirect comparisons in network meta-analysis; heterogeneity in OSA severity across studies."},{"rthcId":"RPEP-15030","title":"Small Intestine-Permeable Cyclic Peptide-Based Technology Enables Efficient Oral Delivery and Glycemic Efficacy of Zinc-Stabilized Insulin Hexamer and Its Analogs in Diabetic Mice.","authors":"Chikamatsu, Shoma; Sakaguchi, Kosei; Michigami, Masataka; Araki, Kimi; Kume, Shoen; Tokuyasu, Midori; Masuda, Takeshi; Fujii, Ikuo; Ohtsuki, Sumio; Ito, Shingo","year":2026,"journal":"Molecular pharmaceutics, 23(1), 252-264","doi":"10.1021/acs.molpharmaceut.5c00902","pmid":"41284288","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"DNP-V cyclic peptide carrier enables efficient oral delivery of zinc-stabilized insulin hexamers with rapid, robust, and sustained glycemic efficacy in diabetic mice.","whyItMatters":"If oral insulin works in humans, it would eliminate billions of daily injections worldwide and dramatically improve diabetes management adherence and quality of life.","specificNumbers":"","methodology":"Peptide engineering of DNP-V carrier; co-administration with zinc-stabilized insulin hexamers; oral dosing in diabetic mouse models; blood glucose monitoring.","limitations":"Mouse model — human intestinal permeability differs significantly; scale-up of peptide carrier manufacturing; bioavailability and dose-response in humans unknown."},{"rthcId":"RPEP-15031","title":"Antimicrobial peptides inhibit Tau aggregation and modulates its pathology.","authors":"Chinnathambi, Subashchandrabose; Rangappa, Nagaraj; Malik, Sneha","year":2026,"journal":"Advances in protein chemistry and structural biology, 149, 375-394","doi":"10.1016/bs.apcsb.2025.09.002","pmid":"41581938","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Antimicrobial peptides directly inhibit tau protein aggregation and modulate Alzheimer's pathology, supporting their dual role as anti-infective and anti-neurodegenerative agents.","whyItMatters":"If antimicrobial peptides naturally protect the brain from both infections and protein aggregation, boosting their production could provide a dual-mechanism Alzheimer's prevention strategy.","specificNumbers":"","methodology":"In vitro tau aggregation assays with antimicrobial peptides; analysis of AMP-tau interactions and effects on pathological aggregation.","limitations":"In vitro study — in vivo effects may differ; not all AMPs may inhibit tau equally; therapeutic AMP delivery to the brain remains a challenge."},{"rthcId":"RPEP-15032","title":"ANIA: an inception-attention network for predicting minimum inhibitory concentration of antimicrobial peptides.","authors":"Chiu, Yen-Peng; Yao, Lantian; Tang, Yun; Chung, Chia-Ru; Pang, Yuxuan; Chiang, Ying-Chih; Lee, Tzong-Yi","year":2026,"journal":"Briefings in bioinformatics, 27(1)","doi":"10.1093/bib/bbag023","pmid":"41664908","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"ANIA deep learning framework predicts AMP MIC values against S. aureus, E. coli, and P. aeruginosa using inception-attention architecture for accurate potency prediction.","whyItMatters":"Predicting how potent a peptide will be against specific bacteria before synthesizing it saves enormous time and money in antimicrobial drug development.","specificNumbers":"","methodology":"Deep learning model development using inception-attention neural network architecture; training and validation on AMP-MIC datasets for three bacterial species.","limitations":"Predictions are model-dependent and may not generalize to all AMP types; limited to three bacterial species; MIC prediction doesn't capture other important drug properties."},{"rthcId":"RPEP-15033","title":"Antimicrobial and therapeutic effect of gold Nanoparticle-Aptamer conjugated antimicrobial peptide RW-BP100 in Brucella canis infected mice and RAW 264.7 cells.","authors":"Cho, Seong Eun; Huy, Tran Xuan Ngoc; Nguyen, Trang Thi; Aguilar, Ched Nicole Turbela; Salad, Said Abdi; Hong, Il-Hwa; Min, Won-Gi; Lee, Hu-Jang; Yeom, Ji-Hyun; Kim, Suk","year":2026,"journal":"Microbial pathogenesis, 210, 108217","doi":"10.1016/j.micpath.2025.108217","pmid":"41338305","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"AuNP-AptHis-RW-BP100His conjugate demonstrated therapeutic efficacy against intracellular Brucella canis in both RAW 264.7 macrophages and infected mice.","whyItMatters":"Brucellosis is a persistent zoonotic disease with limited treatment options. Nanoparticle-delivered AMPs that penetrate infected cells could revolutionize treatment of this and similar intracellular infections.","specificNumbers":"","methodology":"Nanoconjugate synthesis; in vitro macrophage infection model; in vivo mouse brucellosis treatment; antimicrobial efficacy assessment.","limitations":"Mouse model; gold nanoparticle biocompatibility and accumulation need long-term assessment; cost of aptamer-nanoparticle conjugation; single pathogen tested."},{"rthcId":"RPEP-15034","title":"Pathological Degeneration of Disc and Bone Is Associated With Chronic Low Back Pain in a Rat Model With Intradiscal Monosodium Iodoacetate.","authors":"Cho, Yun-Ho; Choi, Cham; Kwon, Minji; Kwon, Jinju; Ok, Hogwang; Ryu, Dawon; Yang, Kyung-Sook; Kim, Junesun; Park, Eui Ho","year":2026,"journal":"Journal of cellular physiology, 241(1), e70140","doi":"10.1002/jcp.70140","pmid":"41572557","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Disc and subchondral bone degeneration correlated with persistent LBP in rats, with neuronal sensitization including CGRP upregulation as a mediating mechanism.","whyItMatters":"Low back pain is the leading cause of disability worldwide. Understanding how structural degeneration drives pain through neuropeptide sensitization could identify new treatment targets.","specificNumbers":"","methodology":"Rat model with intradiscal MIA injection (2 mg); pain behavior assessment over 42 days; structural analysis; neuronal sensitization markers including CGRP.","limitations":"Chemical-induced degeneration model may not fully represent natural aging or injury; rat pain behavior may not translate directly to human pain experience; 42-day timeframe is relatively short."},{"rthcId":"RPEP-15035","title":"Nano-Engineered Delivery of the Pro-Apoptotic KLA Peptide: Strategies, Synergies, and Future Directions.","authors":"Cho, Yunmi; Kim, Ha Gyeong; Oh, Eun-Taex","year":2026,"journal":"Biomolecules, 16(1)","doi":"10.3390/biom16010074","pmid":"41594614","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Multiple nano-engineered delivery platforms can significantly improve the cellular uptake, tumor targeting, and anticancer efficacy of the KLA pro-apoptotic peptide while reducing off-target effects.","whyItMatters":"The KLA peptide has demonstrated strong cancer-killing potential but cannot reach clinical use without effective delivery. These nanocarrier strategies could bridge the gap between laboratory promise and real-world cancer treatment.","specificNumbers":"","methodology":"Narrative review of recent literature on nanocarrier delivery systems for KLA peptide in cancer therapy.","limitations":"As a review, no new experimental data is presented. Most delivery platforms discussed are at preclinical stages. Clinical translation faces challenges including manufacturing scalability, toxicity profiling, and regulatory hurdles for combination nanosystems."},{"rthcId":"RPEP-15036","title":"Development and validation of an LC-MS/MS method for Tirzepatide, a dual GIP/GLP-1 receptor agonist, in rat plasma for application to a pharmacokinetic study.","authors":"Choi, Hae-In; Jeong, Hyeon-Cheol; Jeong, Jong-Woo; Lee, Jaeyoung; Kim, Da Hae; Ko, Kyong-Cheol; Chae, Yoon-Jee; Lee, Kyeong-Ryoon","year":2026,"journal":"Journal of chromatography. B, Analytical technologies in the biomedical and life sciences, 1268, 124836","doi":"10.1016/j.jchromb.2025.124836","pmid":"41197390","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A sensitive LC-MS/MS method was developed and validated for tirzepatide quantification in rat plasma using protein precipitation extraction and peptide C18 column chromatography.","whyItMatters":"Reliable blood level measurement is essential for understanding how tirzepatide behaves in the body, informing dose optimization and safety studies for this important dual-agonist drug.","specificNumbers":"","methodology":"Analytical method development and validation following bioanalytical guidelines; LC-MS/MS with protein precipitation; application to rat pharmacokinetic study.","limitations":"Validated in rat plasma only — may need modification for human plasma; method complexity requires specialized equipment; single peptide drug validated."},{"rthcId":"RPEP-15037","title":"Convergent Metabolic Pathways in MASH Therapeutics: An AMPK-Centric Analysis.","authors":"Choi, Seungchan; Jung, Jin-Seok; Seo, Yie-Sung; Song, Sungmin; Ham, Jeehye; Chung, Hannah; Ramadan, Yousef; Choi, Kangchan","year":2026,"journal":"Journal of cellular and molecular medicine, 30(2), e71023","doi":"10.1111/jcmm.71023","pmid":"41545323","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Diverse MASH therapeutics including resmetirom and GLP-1 RAs converge on AMPK signaling, providing a unified mechanistic framework for understanding their therapeutic effects.","whyItMatters":"MASH affects millions and just entered its first era of effective treatments. Understanding that multiple drugs work through AMPK could guide rational combination therapy and new drug design.","specificNumbers":"","methodology":"Mechanistic review proposing an AMPK-centric framework for understanding convergent MASH drug mechanisms.","limitations":"Framework is proposed rather than experimentally validated; AMPK activation may not explain all drug effects; some MASH therapies may work through AMPK-independent pathways."},{"rthcId":"RPEP-15038","title":"Comparative efficacy and safety of liraglutide versus metformin, naltrexone/bupropion, and phentermine-topiramate in psychiatric patients.","authors":"Choi, Won-Seok; Song, Min-Kyu; Seo, Mansuk; Woo, Young Sup; Bahk, Won-Myong","year":2026,"journal":"Therapeutic advances in psychopharmacology, 16, 20451253261419609","doi":"10.1177/20451253261419609","pmid":"41727810","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Comparative effectiveness analysis of four anti-obesity medications in psychiatric patients revealed differences in weight loss, adverse events, and early discontinuation rates in this understudied population.","whyItMatters":"Psychiatric patients face unique challenges with weight management — their medications cause weight gain, some drugs interact with psychiatric medications, and mental health conditions affect adherence. Evidence specific to this population is critical.","specificNumbers":"","methodology":"Retrospective observational cohort study comparing liraglutide, metformin, naltrexone/bupropion, and phentermine-topiramate in psychiatric outpatients.","limitations":"Retrospective observational design; selection bias likely; short-term outcomes only; psychiatric diagnoses and medications not standardized across groups."},{"rthcId":"RPEP-15039","title":"Unintentional periconceptional exposure to glucagon-like peptide-1 receptor agonists and adverse pregnancy outcomes: A nationwide cohort study in Taiwan.","authors":"Chou, Yi-Chang; Weng, Shih-Han; Cheng, Feng-Shiang; Tseng, Chih-Hao; Hu, Hsiao-Yun; Liu, Chieh-Hsing","year":2026,"journal":"Diabetes, obesity & metabolism, 28(2), 1420-1430","doi":"10.1111/dom.70334","pmid":"41346258","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The nationwide cohort study assessed associations between periconceptional GLP-1 RA exposure and adverse pregnancy outcomes in women with pregestational T2DM compared to insulin users.","whyItMatters":"Millions of reproductive-age women now take GLP-1 drugs. Understanding pregnancy risks from accidental exposure around conception is critical for counseling and prescribing guidelines.","specificNumbers":"","methodology":"Nationwide cohort study linking Taiwan's Birth Certificate Application and National Health Insurance claims 2013-2022; periconceptional GLP-1 RA exposure vs insulin.","limitations":"Observational database study; exposure defined by dispensing, not actual use; confounding by diabetes severity; Taiwan population may differ from others."},{"rthcId":"RPEP-15040","title":"Streptococcus pneumoniae upregulates Toll2, Toll9, and defensin genes in Bombyx larvae infection model.","authors":"Chowdhury, Farhan R; Hossain, M Ismail; Jepu, Tangerul A; Saleh, Nusrat U A; Zohora, Fatema T; Saleh, Tasmim A; Sarker, Mrinmoy; Numan, Al; Yousuf, Zainab; Uddin, M Aftab; Hossain, Muktadir S","year":2026,"journal":"PloS one, 21(1), e0341929","doi":"10.1371/journal.pone.0341929","pmid":"41616027","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"S. pneumoniae infection upregulates Toll2, Toll9, and defensin genes in Bombyx larvae, confirming conserved innate immune responses and validating this insect model for pneumococcal research.","whyItMatters":"Using insect models for pneumococcal research is faster, cheaper, and more ethical than mammalian studies. Validating that conserved immune pathways respond similarly enables high-throughput pathogen research.","specificNumbers":"","methodology":"Whole genome sequencing of clinical S. pneumoniae isolate; Bombyx mori larvae infection model; immune gene expression analysis.","limitations":"Insect model lacks adaptive immunity; host-specific virulence factors may not be relevant; cannot model respiratory tract infection directly."},{"rthcId":"RPEP-15041","title":"The efficacy of rimegepant for the acute treatment of vestibular migraine.","authors":"Chu, Heling; Pan, Jingwei; Huang, Chuyi","year":2026,"journal":"Scientific reports","doi":"10.1038/s41598-026-39902-9","pmid":"41699085","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Rimegepant 75 mg effectively treated acute vestibular migraine symptoms including vertigo, unsteadiness, nausea/vomiting, photo/phonophobia, and headache.","whyItMatters":"Vestibular migraine is the most common cause of episodic vertigo, affecting millions, yet has no FDA-approved treatment. Demonstrating rimegepant efficacy could change clinical practice.","specificNumbers":"","methodology":"Clinical study of rimegepant 75 mg for acute VM attacks; patients meeting VM/probable VM criteria; 5 symptom severity ratings (0-3 scale) at multiple time points.","limitations":"Likely open-label without placebo control; sample size may be small; short-term acute treatment only; VM diagnostic criteria overlap makes patient selection challenging."},{"rthcId":"RPEP-15042","title":"GLP-1RA Dispensing in Youth With Type 2 Diabetes: 2020 to 2023.","authors":"Chu, Patricia Y; Kelly, Andrea; Hennessy, Sean; Vajravelu, Mary Ellen; Huang, Jing; Amaral, Sandra","year":2026,"journal":"Pediatrics","doi":"10.1542/peds.2025-071971","pmid":"41765350","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1RA dispensing increased in youth with T2D from 2020-2023, but significant disparities existed between Medicaid and commercially insured youth.","whyItMatters":"Type 2 diabetes in youth is increasing rapidly, especially in disadvantaged populations. If Medicaid-insured kids can't access GLP-1 drugs, health disparities will widen at the youngest ages.","specificNumbers":"","methodology":"Multi-year cross-sectional study using Merative MarketScan Medicaid and Commercial databases; youth 10-17 with T2D; GLP-1 RA dispensing trends.","limitations":"Claims data may not capture all prescriptions; dispensing doesn't confirm adherence; can't assess clinical outcomes; database may not represent all US youth."},{"rthcId":"RPEP-15043","title":"Amylin Revisited: A 5-Year Perspective on Its Emerging Role in the Treatment of Diabesity.","authors":"Chung, Chae Won; Kim, Jaetaek","year":2026,"journal":"Journal of obesity & metabolic syndrome, 35(1), 38-48","doi":"10.7570/jomes25085","pmid":"41549439","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Cagrilintide combined with GLP-1 receptor agonists achieves synergistic weight loss exceeding 15%, positioning amylin analogs as key players in diabesity treatment.","whyItMatters":"Obesity and diabetes together (diabesity) are a growing global epidemic. Amylin analogs offer a new hormonal pathway to complement GLP-1 drugs, potentially achieving weight loss and glucose control that neither achieves alone.","specificNumbers":"","methodology":"Narrative review of preclinical and clinical studies on amylin physiology and analog development over the past five years.","limitations":"Review article without new primary data. Long-term safety and durability of amylin analog effects still need confirmation from large phase 3 trials."},{"rthcId":"RPEP-15044","title":"Topical Carrier-Free Delivery of Finasteride and Peptides for Enhanced Hair Growth.","authors":"Chung, Won Young; Kim, Ji-Eun; Lee, Jae Yun; Kim, Suin; Jeong, Woo-Jin","year":2026,"journal":"Biomacromolecules, 27(2), 1300-1309","doi":"10.1021/acs.biomac.5c01874","pmid":"41492731","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Peptide-finasteride nanocomplexes promoted hair regeneration comparable to 5% minoxidil in vivo, using approximately 40-fold less finasteride than the standard oral dose.","whyItMatters":"Finasteride oral side effects limit its use for hair loss. This topical approach could retain efficacy while dramatically reducing systemic drug exposure, potentially making finasteride safer for long-term use.","specificNumbers":"","methodology":"Preclinical study using cell viability assays, in vivo murine hair regrowth models, and biochemical analysis of follicle cycling.","limitations":"Preclinical (mouse model) only; human clinical trials are needed. Differences in human vs. murine hair biology may affect translation."},{"rthcId":"RPEP-15045","title":"Semaglutide as adjunctive therapy to catheter ablation in obesity-related paroxysmal atrial fibrillation.","authors":"Ciconte, Giuseppe; Salerno, Raffaele; Fuga, Alessandro; Vuturo, Alessia; Boccellino, Antonio; Negro, Gabriele; Rondine, Roberto; Ballarotto, Marco; Ciaccio, Cristiano; Izzo, Antonio; Morciano, Davide Antonio; Garbelli, Arianna; Giannelli, Luigi; Maiolo, Vincenzo; Calovic, Zarko; Anastasia, Luigi; Pappone, Carlo","year":2026,"journal":"Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology, 28(2)","doi":"10.1093/europace/euag018","pmid":"41666150","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide as adjunct to AF catheter ablation reduced arrhythmia recurrence (HR 0.52, 95% CI 0.34–0.78) with freedom from recurrence of 80.2% vs. 65.2% at 18 months.","whyItMatters":"Obesity is a major driver of AF recurrence after ablation. This study suggests semaglutide could transform post-ablation care by addressing the underlying metabolic driver, not just the electrical problem.","specificNumbers":"","methodology":"Single-center propensity-matched study with 362 obese patients (181 per group) undergoing first-time catheter ablation, monitored by implantable cardiac monitors.","limitations":"Single-center, non-randomized study; propensity matching cannot eliminate all confounders. Continuous monitoring via implantable devices is a strength but the study population may not generalize to all AF patients."},{"rthcId":"RPEP-15046","title":"Calcitonin Gene-Related Peptide (CGRP) Expression in Somatotroph Adenomas: Implications for Clinical Course and Treatment Outcomes.","authors":"Cil, Sanem; Pekmezci, Aslihan; Karatay, Huseyin; Dogukan, Fatih Mert; Burhan, Sebnem; Cil, Mehmet Said; Akpinar, Ebubekir; Erkan, Buruc; Niyazoglu, Mutlu; Hatipoglu, Esra","year":2026,"journal":"Neuroendocrinology, 1-17","doi":"10.1159/000551012","pmid":"41746852","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CGRP was expressed in 50% of acromegaly adenomas and 0% of nonfunctioning pituitary adenomas (p<0.001). CGRP-positive tumors showed trends toward higher chronic headache rates (40% vs 13%) and lower postoperative remission (60% vs 86.7%).","whyItMatters":"This finding connects CGRP—already a validated target for migraine therapy—to pituitary tumor biology, potentially explaining why some acromegaly patients experience persistent headaches and suggesting CGRP-targeted treatments could have a role in managing these symptoms.","specificNumbers":"","methodology":"Retrospective immunohistochemistry study of surgical pituitary adenoma tissue samples from 49 patients (30 acromegaly, 19 NFPA) at a single center, with clinical, radiological, and histopathological correlation.","limitations":"Small sample size (49 patients) limits statistical power—key associations showed trends (p=0.07-0.09) but did not reach significance. Single-center design, retrospective analysis. Functional role of CGRP in adenoma biology was not directly tested."},{"rthcId":"RPEP-15047","title":"Development of a quadruple-conjugated carbon dot nanomodel for targeted glioma therapy.","authors":"Cilingir, Emel Kirbas; Hettiarachchi, Sajini D; Rathee, Parth; Zhou, Yiqun; Ferreira, Braulio Clb; Wang, Lukun; Joji, Annu; Gonzalez, Carlos M; Moreno Hollweg, Maria J; Shiri, Mehrdad; Wang, Kun; Prabhakar, Rajeev; Vanni, Steven; Leblanc, Roger M; Graham, Regina M","year":2026,"journal":"Communications chemistry, 9(1), 96","doi":"10.1038/s42004-026-01900-3","pmid":"41618001","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Quadruple-conjugated carbon dot nanomodel showed potent glioma cytotoxicity at 50 nM with >40-fold selectivity over normal cells, establishing a modular platform for targeted brain cancer therapy.","whyItMatters":"High-grade gliomas have dismal prognosis partly because drugs cannot cross the blood-brain barrier or distinguish tumor from healthy tissue. This modular platform addresses both problems simultaneously.","specificNumbers":"","methodology":"Preclinical study using one-pot synthesis of functionalized carbon dots, with in vitro cytotoxicity assays across multiple glioma and normal cell lines, plus fluorescence uptake studies.","limitations":"In vitro only; no in vivo or blood-brain barrier crossing data. Drug-loading capacity was lower than single-peptide formulations. Clinical translation faces significant regulatory and manufacturing hurdles."},{"rthcId":"RPEP-15048","title":"The Role and Progress of Antimicrobial Peptides in Managing Oral Biofilms: A Narrative Review.","authors":"Ciren, Deji; Xia, Xiaoyue; Zhu, Yuemeng; Hui, Sumin; Hong, Lihua","year":2026,"journal":"International dental journal, 76(1), 104022","doi":"10.1016/j.identj.2025.104022","pmid":"41237593","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"AMPs demonstrate effective disruption of cariogenic, periodontal, root canal, peri-implantitis, and Candida-associated oral biofilms with minimal resistance development.","whyItMatters":"Antibiotic resistance is making oral infections harder to treat. AMPs represent a fundamentally different antimicrobial approach that could reshape dental therapeutics if stability and delivery challenges are overcome.","specificNumbers":"","methodology":"Narrative review synthesizing laboratory and preclinical studies on AMP mechanisms and applications against oral biofilms.","limitations":"Mostly preclinical evidence; AMP stability in the oral environment (saliva, enzymes, pH) remains a challenge. Cost and scalability of peptide production may limit clinical adoption."},{"rthcId":"RPEP-15049","title":"Effectiveness and safety of combining SGLT2 inhibitors and GLP-1 receptor agonists in individuals with type 2 diabetes: a systematic review and meta-analysis of cohort studies.","authors":"Colombijn, Julia M T; de Leijer, Jan F; Visseren, Frank L J; Verhaar, Marianne C; van Raalte, Daniël H; Sattar, Naveed; Vernooij, Robin W M; van Sloten, Thomas T","year":2026,"journal":"Diabetologia, 69(1), 36-49","doi":"10.1007/s00125-025-06565-6","pmid":"41117973","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Combination SGLT2i + GLP-1 RA therapy reduced MACE by 44% (RR 0.56), cardiovascular mortality by 74% (RR 0.26), and kidney composite endpoint by 52% (RR 0.48) vs. monotherapy.","whyItMatters":"This is the strongest real-world evidence yet that combining these two drug classes produces additive or synergistic cardiorenal protection, supporting dual therapy as a potential new standard for high-risk diabetic patients.","specificNumbers":"","methodology":"Systematic review and meta-analysis of 18 cohort studies (1,164,774 participants) with GRADE certainty assessment and ROBINS-I bias evaluation.","limitations":"All observational studies; residual confounding cannot be excluded. Evidence certainty rated low to very low by GRADE. Safety data were too sparse to pool."},{"rthcId":"RPEP-15050","title":"Anti-inflammatory Pathways of Novel Anti-diabetic Therapies. A Literature Review.","authors":"Comșa, Adina David; Comșa, Horațiu; Cismaru, Gabriel; Roșu, Radu; Pop, Dana","year":2026,"journal":"In vivo (Athens, Greece), 40(1), 600-627","doi":"10.21873/invivo.14224","pmid":"41482411","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Both SGLT2i and GLP-1 RAs exert cardiovascular protection through multiple anti-inflammatory pathways including cytokine reduction, oxidative stress mitigation, immune modulation, and endothelial function improvement.","whyItMatters":"Understanding why these diabetes drugs protect the heart—beyond blood sugar control—could enable their use in non-diabetic cardiovascular disease and guide development of more targeted therapies.","specificNumbers":"","methodology":"Descriptive literature review of anti-inflammatory mechanisms of SGLT2 inhibitors and GLP-1 receptor agonists.","limitations":"Descriptive review without systematic methodology. Many mechanistic studies are preclinical; clinical translation of individual anti-inflammatory pathways is not fully established."},{"rthcId":"RPEP-15051","title":"Metabolite Profiling and Identification of Semaglutide in Liver S9 Across Species and Rat Plasma.","authors":"Cong, Yawen; Tang, Chongzhuang; Li, Zhiqiang; Gao, Yang; Chen, Lijuan; Xu, Haibo; Diao, Xingxing","year":2026,"journal":"Biomedical chromatography : BMC, 40(4), e70415","doi":"10.1002/bmc.70415","pmid":"41787929","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"31 semaglutide metabolites identified across five species, with peptide backbone hydrolysis as the primary metabolic pathway and a diagnostic m/z 469 fragment enabling efficient screening.","whyItMatters":"Understanding how peptide drugs are metabolized is critical for safety and efficacy assessment. This method fills a gap in peptide drug development by providing a reliable in vitro screening model.","specificNumbers":"","methodology":"In vitro liver S9 incubation across 5 species plus in vivo rat plasma analysis using UHPLC-HRMS with data-dependent acquisition.","limitations":"Liver S9 fractions do not capture all in vivo metabolic pathways (e.g., kidney metabolism, gut microbiome). The rat in vivo dose (10 mg/kg) far exceeds clinical human doses."},{"rthcId":"RPEP-15052","title":"Evexomostat (SDX-7320), a methionine aminopeptidase type 2 inhibitor, stimulates weight loss and inhibits obesity-accelerated tumor growth.","authors":"Cornelius, Peter; Mayes, Benjamin A; Dannenberg, Andrew J; Dufour, Pierre J; Little, Sara; Guzior, Douglas V; Petersen, John S; Shanahan, James M; Carver, Bradley J","year":2026,"journal":"Frontiers in oncology, 16, 1751681","doi":"10.3389/fonc.2026.1751681","pmid":"41789003","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"SDX-7320 significantly attenuated obesity-accelerated tumor growth in three syngeneic mouse models and outperformed tirzepatide for tumor inhibition despite causing less weight loss, indicating direct anti-tumor mechanisms.","whyItMatters":"Obesity-associated cancers represent a growing clinical challenge. A drug that addresses both obesity and directly fights tumors could fill an unmet need, and this study provides the first evidence that METAP2 inhibition can do both.","specificNumbers":"","methodology":"Preclinical study using diet-induced obese mice and rats with syngeneic tumor models (B16F10, EO771, MC38), pharmacokinetic-pharmacodynamic analysis, RNA-Seq tumor profiling, and plasma metabolomics.","limitations":"Entirely preclinical (mouse/rat models) — results may not translate to humans. Syngeneic tumor models don't perfectly replicate human cancer biology. No human safety or efficacy data presented. Long-term effects unknown."},{"rthcId":"RPEP-15053","title":"Clinical Impact of Semaglutide Beyond Glycemic Control: A Critical Analysis of Oncogenic Potential and Mitigation of Cardiotoxicity.","authors":"Correra, Adriana; Mauriello, Alfredo; Cetoretta, Valeria; Maratea, Anna Chiara; Riegler, Lucia; Di Sarno, Isabella; Giallauria, Francesco; Guerra, Federico; Russo, Vincenzo; D'Andrea, Antonello","year":2026,"journal":"Pharmaceuticals (Basel, Switzerland), 19(2)","doi":"10.3390/ph19020297","pmid":"41754837","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Human epidemiological data do not confirm the thyroid or pancreatic cancer risks seen in rodent models, and semaglutide's anti-inflammatory and cardioprotective properties may offer additional clinical value beyond metabolic control.","whyItMatters":"Millions of people take semaglutide for diabetes and obesity. Understanding its long-term cancer risk profile and potential heart-protective benefits is critical for informed prescribing and patient reassurance.","specificNumbers":"","methodology":"Narrative review analyzing clinical trial data, post-marketing surveillance reports, and meta-analyses on semaglutide's oncogenic potential and cardioprotective effects.","limitations":"Narrative review without new primary data. Human exposure to semaglutide at scale is relatively recent, so long-term cancer risk may not be fully captured. The cardioprotective potential in cancer therapy contexts needs prospective validation."},{"rthcId":"RPEP-15054","title":"Tirzepatide in solid organ transplant recipients: Early real-world signals of efficacy and safety-A narrative review.","authors":"Corrêa, Lucas Maciel de Almeida; Mazur, Gabriel Rian; Santiago, Clara Belo Gamon; Dante, Letícia Esteves; de Marco, Patrícia Silva; Ferrés, Paola Beatriz Souza","year":2026,"journal":"Transplantation reviews (Orlando, Fla.), 40(2), 101003","doi":"10.1016/j.trre.2026.101003","pmid":"41707409","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 182 transplant recipients, tirzepatide reduced HbA1c by 0.6-1.4 percentage points and body weight by 5.5-6.9 kg while maintaining stable tacrolimus levels (Δ -0.2 to +0.2 ng/mL) with no rejection signals.","whyItMatters":"Transplant recipients face heightened metabolic risks but have been largely excluded from GLP-1 drug trials. This early evidence suggests tirzepatide can safely provide metabolic benefits without jeopardizing the transplanted organ.","specificNumbers":"","methodology":"Narrative review with structured database search identifying 10 reports, with quantitative analysis limited to 6 studies (n=182) providing disaggregated tirzepatide data.","limitations":"All included studies are retrospective with small sample sizes. No randomized controlled trials. Long-term graft outcomes and safety data are unavailable. Publication bias toward positive results is possible."},{"rthcId":"RPEP-15055","title":"Impact of GLP-1 receptor agonists on stroke, subarachnoid hemorrhage, and intracerebral hemorrhage: a propensity-matched multi-institutional cohort study.","authors":"Costa, Matias; O'Leary, Sean; Price, Anthony M; Young, Christopher C; Srinivasan, Visish M; Kan, Peter","year":2026,"journal":"Journal of neurosurgery, 144(2), 428-441","doi":"10.3171/2025.5.JNS25786","pmid":"41043189","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 receptor agonists were associated with 56-73% lower mortality across stroke types, 27-30% lower rebleeding rates, and 18-38% reduced incidence of new strokes at 1-2 year follow-up.","whyItMatters":"Stroke remains a leading cause of death and disability worldwide. If GLP-1 drugs can truly improve stroke outcomes and prevent recurrence, they could become an important part of stroke management beyond their metabolic benefits.","specificNumbers":"","methodology":"Retrospective propensity-matched multi-institutional cohort study using TriNetX data (2014-2024), analyzing patients receiving GLP-1-RAs within 8 weeks of stroke diagnosis versus matched controls.","limitations":"Retrospective observational design cannot prove causation. Patients on GLP-1 drugs may have better overall healthcare engagement. Selection bias possible despite propensity matching. The 8-week drug exposure window around diagnosis may capture patients already on therapy rather than newly prescribed."},{"rthcId":"RPEP-15056","title":"Exploring immobilization strategies of antimicrobial peptides onto MAO-treated titanium to fight MRSA colonization and preserve osteogenic activity.","authors":"Costa, Natália A; Monteiro, Cláudia; Grenho, Liliana; Ribeiro, Ana R; Leiro, Victoria; Fernandes, Maria H; Lisboa-Filho, Paulo N; Martins, M Cristina L","year":2026,"journal":"Materials today. Bio, 37, 102896","doi":"10.1016/j.mtbio.2026.102896","pmid":"41732386","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"PEGylated MAO titanium surfaces with adsorbed MSI-78 peptide reduced MRSA colonization and killed ~80% of adherent bacteria while maintaining full cytocompatibility with bone-like cells and supporting osteogenic response.","whyItMatters":"Implant-associated MRSA infections are devastating and increasingly resistant to antibiotics. Antimicrobial peptide coatings that fight infection without compromising bone healing could prevent costly revision surgeries and improve patient outcomes.","specificNumbers":"","methodology":"Proof-of-concept in vitro study comparing three peptide immobilization strategies (physical adsorption, CDI covalent grafting, PEG spacer + adsorption) on MAO-treated titanium, with MRSA challenge and bone cell compatibility assays.","limitations":"In vitro study only—no animal or human testing. Long-term peptide stability on the surface not assessed. The pre-conditioning with human plasma proteins simulates but doesn't fully replicate in vivo conditions. Single bacterial strain tested."},{"rthcId":"RPEP-15057","title":"Electrophysiological modulation of cholinergic neurotransmission by biologically active peptides from Bothrops bilineatus (Viperidae: Crotalinae) venom.","authors":"Couceiro, Fernanda Y G M; Pacagnelli, Francis L; Torres-Bonilla, Kristian A; Hyslop, Stephen; Lomonte, Bruno; Drummond, Robert M; Pimenta, Daniel C; Borges, Rafael J; Floriano, Rafael S","year":2026,"journal":"Archives of toxicology, 100(1), 341-354","doi":"10.1007/s00204-025-04176-z","pmid":"41015986","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tripeptide P8-1 (pEKW) from B. bilineatus venom increased miniature end-plate potential frequency at the neuromuscular junction, representing the first identified bioactive tripeptides with presynaptic effects in Viperidae venom.","whyItMatters":"Venom-derived peptides are valuable templates for drug development. These uniquely small neuromodulatory peptides could serve as tools for studying synaptic physiology and as starting points for designing novel neuroactive therapeutics.","specificNumbers":"","methodology":"Venom fractionation by size-exclusion chromatography, mass spectrometry identification, and electrophysiological analysis using mouse phrenic nerve-diaphragm preparations.","limitations":"In vitro mouse tissue preparation only. The exact mechanism of presynaptic facilitation is not fully characterized. Translation to therapeutic applications requires extensive further development."},{"rthcId":"RPEP-15058","title":"The venom gland transcriptome of Tityus paraguayensis reveals a diverse array of bioactive molecules from the Brazilian Cerrado.","authors":"Covali-Pontes, Henrique Ranieri; Meneguelli, Brayhan; Carretone, Jéssica de Moraes; Ribeiro, Alynne Coelho; Santos, Angélica Camargo Dos; Carlos, Thais Fernanda; Chiaratti, Marcos Roberto; Ferro, Milene; Silva, Flávio Henrique; Rodrigues, Renata Dos Santos; Lucena, Malson Neilson","year":2026,"journal":"PloS one, 21(2), e0343107","doi":"10.1371/journal.pone.0343107","pmid":"41719282","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"523 venom-related transcripts identified, with the potassium toxin TpK8 showing high-affinity binding to the Kv1.3 channel selectivity filter through molecular docking analysis.","whyItMatters":"Scorpion venom peptides that modulate ion channels are valuable leads for developing drugs targeting neurological and autoimmune conditions. The Kv1.3 channel in particular is a drug target for autoimmune diseases like multiple sclerosis.","specificNumbers":"","methodology":"Venom gland transcriptome sequencing and assembly, functional annotation, 3D structural modeling, phylogenetic analysis, and molecular docking of selected peptides.","limitations":"Transcriptome analysis identifies gene expression but doesn't confirm all transcripts produce functional proteins. Molecular docking is computational prediction requiring experimental validation. No in vivo efficacy testing performed."},{"rthcId":"RPEP-15059","title":"Comparative Gastrointestinal Safety of Dulaglutide, Semaglutide, and Tirzepatide in Adults With Type 2 Diabetes.","authors":"Crisafulli, Salvatore; Alkabbani, Wajd; Paik, Julie M; Bykov, Katsiaryna; Tavakkoli, Ali; Glynn, Robert J; Htoo, Phyo T; Yu, Elaine W; Trifirò, Gianluca; Wexler, Deborah J; Patorno, Elisabetta","year":2026,"journal":"Annals of internal medicine, 179(1), 1-11","doi":"10.7326/ANNALS-25-01724","pmid":"41183330","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"No significant differences in composite GI adverse events were found: semaglutide vs dulaglutide HR 0.96 (0.87-1.06), tirzepatide vs dulaglutide HR 0.96 (0.77-1.20), tirzepatide vs semaglutide HR 1.07 (0.90-1.26).","whyItMatters":"Patients and clinicians often worry about GI side effects when choosing between GLP-1 drugs. This evidence showing equivalent safety profiles allows treatment decisions to be based on other factors like efficacy and cost.","specificNumbers":"","methodology":"New-user, active-comparator cohort study with 1:1 propensity score matching across three pairwise comparisons using population-based data from January 2019 to August 2024.","limitations":"Possible residual confounding by glycemic control and BMI. Observational design. May not capture milder GI symptoms that don't result in medical encounters or diagnoses."},{"rthcId":"RPEP-15060","title":"Hyaluronic acid-ethylenediamine-cinnamic acid attenuates IBS-D via regulating 5-hydroxytryptamine signaling pathway, intestinal barrier and gut microbiota.","authors":"Cui, Li; Zhong, Rongling; Peng, Wanqiu; Zhang, Zhenhai; An, Zhentao; Li, Hui","year":2026,"journal":"International journal of biological macromolecules, 348, 150694","doi":"10.1016/j.ijbiomac.2026.150694","pmid":"41643969","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15061","title":"Design of biomimetic chylomicrons based on 1,3-diolein grafted hyaluronic acid to drive biomacromolecules across the intestinal mucosal barrier.","authors":"Cui, Shuman; An, Yalin; Cui, Zhixiang; Liu, Shiyun; Li, Hongfang; Wen, Xiangce; Guan, Jian; Mao, Shirui; Yi, Han; Zhang, Xin","year":2026,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 390, 114504","doi":"10.1016/j.jconrel.2025.114504","pmid":"41352647","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Core-shell nanoparticles mimicking chylomicrons achieved 9.67% pharmacological bioavailability for oral exenatide, with 5.6-fold increased intestinal permeability and persistent hypoglycemic effects in type 2 diabetic rats.","whyItMatters":"Most peptide drugs require injection because they can't survive the GI tract. An oral delivery system achieving ~10% bioavailability could eliminate the need for daily or weekly injections of GLP-1 drugs, dramatically improving patient compliance.","specificNumbers":"","methodology":"In vitro characterization of HA-DOG/EAZ nanoparticles (enzymatic stability, mucosal penetration, intestinal permeability), followed by in vivo pharmacokinetic and pharmacodynamic studies in type 2 diabetic rats.","limitations":"Only tested in rats; human GI conditions differ significantly. 9.67% bioavailability, while impressive for oral peptides, still means over 90% of the drug is lost. Manufacturing scalability not addressed. Long-term safety of the nanoparticle system unknown."},{"rthcId":"RPEP-15062","title":"Physiology, Vasopressin","authors":"Cuzzo, Brian; Padala, Sandeep A.; Lappin, Sarah L.; Lauridsen, Henrik H; Hartvigsen, Jan; Korsholm, Lars; Grunnet-Nilsson, Niels; Manniche, Claus","year":2026,"journal":"Pain, 131(1-2), 112-20","doi":null,"pmid":"30252325","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15063","title":"Cathelicidin-like Peptide for Resistant Acinetobacter baumannii Control.","authors":"Cândido, Elizabete de Souza; Buccini, Danieli Fernanda; Miranda, Elizangela de Barros; Gonçalves, Regina Meneses; Brandão, Amanda Loren de Oliveira; Nieto-Marín, Valentina; Leal, Ana Paula Ferreira; Rezende, Samilla Beatriz; Cardoso, Marlon Henrique; Franco, Octavio Luiz","year":2026,"journal":"Antibiotics (Basel, Switzerland), 15(1)","doi":"10.3390/antibiotics15010077","pmid":"41594114","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A cathelicidin-like antimicrobial peptide demonstrated effective activity against multidrug-resistant Acinetobacter baumannii, disrupting biofilm formation in wound infection models.","whyItMatters":"A. baumannii wound infections have mortality rates up to 40% and are running out of antibiotic options. New antimicrobial peptides could save lives.","specificNumbers":"","methodology":"Development and evaluation of a cathelicidin-like AMP against multidrug-resistant A. baumannii, testing antimicrobial and anti-biofilm activity in wound infection contexts.","limitations":"In vitro and wound model testing — clinical efficacy and safety in human wound infections not yet established."},{"rthcId":"RPEP-15064","title":"Nous-209 neoantigen vaccine for cancer prevention in Lynch syndrome carriers: a phase 1b/2 trial.","authors":"D'Alise, Anna Morena; Willis, Jason; Duzagac, Fahriye; Hall, Michael J; Cruz-Correa, Marcia; Idos, Gregory E; Thirumurthi, Selvi; Ballester, Veroushka; Leoni, Guido; Garzia, Irene; Antonucci, Laura; De Marco, Lorenzo; Micarelli, Elisa; Deng, Nan; Seclì, Laura; Gogov, Sven; Dong, Wenli; Jack Lee, J; Bowen, Charles M; Vornik, Lana A; Garcia-Gonzalez, Araceli; Reyes-Uribe, Laura; Richmond, Ellen; Umar, Asad; Brown, Powel H; Sinha, Krishna M; Rodriguez, Luz Maria; Scarselli, Elisa; Vilar, Eduardo","year":2026,"journal":"Nature medicine","doi":"10.1038/s41591-025-04182-9","pmid":"41545594","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"100% of evaluable participants (37/37) developed neoantigen-specific immune responses, with a mean peak of ~1,100 interferon-γ spot-forming cells per million PBMCs, and 85% maintained detectable immunity at one year.","whyItMatters":"If this vaccine can prevent cancer in Lynch syndrome carriers, it would represent a paradigm shift from treating cancer to intercepting it before it develops—potentially benefiting millions of people with this common genetic condition.","specificNumbers":"","methodology":"Phase 1b/2 single-arm clinical trial (NCT05078866) with 45 Lynch syndrome carriers receiving heterologous prime-boost vaccination. Safety and immunogenicity were coprimary endpoints.","limitations":"Phase 1b/2 trial — cancer prevention efficacy cannot be assessed from immunogenicity data alone. Single-arm design without placebo control. Small sample size. Long-term cancer incidence outcomes are still pending."},{"rthcId":"RPEP-15065","title":"Association of glucagon-like peptide-1 agonist therapy with postsurgical outcomes following multilevel correction for adult spinal deformity: a propensity score-matched analysis.","authors":"D'Amico, Cassandra; Jacques, Benjamin; Ferdon, Robert; Silvestre, Jason; Lewis, Stephen; Nielsen, Christopher; Glaser, John; Reitman, Charles; Lawrence, James; Ravinsky, Robert","year":2026,"journal":"Asian spine journal","doi":"10.31616/asj.2025.0407","pmid":"41490720","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"At 1 and 2 years post-surgery, GLP-1 agonist users had significantly lower odds of pseudoarthrosis, hardware failures, wound dehiscence, infections, thromboembolic events, readmissions, and mortality after spinal deformity correction.","whyItMatters":"Spinal deformity surgery has high complication rates. If GLP-1 drugs truly reduce these complications, they could become an important part of surgical preparation and recovery protocols for spine patients.","specificNumbers":"","methodology":"Multicenter retrospective cohort study using the TriNetX Global Collaborative Database (2005-2025) with 1:1 propensity-score matching by demographics and comorbidities.","limitations":"Retrospective observational design. Patients on GLP-1 drugs may differ systematically from non-users in ways not captured by propensity matching. The mechanism by which GLP-1 drugs improve surgical outcomes is not established."},{"rthcId":"RPEP-15066","title":"Peptide Nucleic Acids (PNAs) in Antimicrobial Therapy: A Next Generation Strategy.","authors":"D'Aniello, Antonia; Masi, Annalisa; Avitabile, Concetta; Del Monaco, Giovanni; Saviano, Michele; Moccia, Maria","year":2026,"journal":"International journal of molecular sciences, 27(3)","doi":"10.3390/ijms27031565","pmid":"41683983","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"PNAs demonstrate species-specific antimicrobial activity through targeted gene silencing, with recent delivery advances (cell-penetrating peptides, dendron conjugates, nanoparticles) significantly improving their therapeutic potential.","whyItMatters":"Antimicrobial resistance is a global health crisis. PNAs offer a fundamentally different approach—targeting genes rather than proteins—that could be customized to fight specific resistant bacteria without contributing to broader resistance.","specificNumbers":"","methodology":"Narrative review of in vitro and in vivo studies on PNA-based antimicrobial strategies, including delivery platform development and combination therapy approaches.","limitations":"Most evidence is from in vitro studies; in vivo data remain limited. Delivery to bacterial cells inside the body remains challenging. Large-scale production is costly. Clinical trials are needed."},{"rthcId":"RPEP-15067","title":"Impact of Adjuvant GLP-1RA Treatment on the Adherence of Second-Generation Antipsychotics in Nondiabetic Adults.","authors":"Daggolu, Jerusha; Okonkwo, Michael; Chen, Hua","year":2026,"journal":"Journal of clinical psychopharmacology","doi":"10.1097/JCP.0000000000002145","pmid":"41676872","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Adjuvant GLP-1RA improved antipsychotic adherence with 8.91% higher PDC (commercial) and 19.80% higher PDC (Medicaid), and 27.12 and 41.21 additional days of persistence, respectively.","whyItMatters":"Poor antipsychotic adherence is a major driver of psychiatric relapse and hospitalization. If GLP-1 drugs can keep patients on their medications by managing weight gain, this could significantly improve psychiatric outcomes and reduce healthcare costs.","specificNumbers":"","methodology":"Retrospective cohort study using MarketScan Commercial and Medicaid claims (2019-2023) with prescription-time-distribution matching and propensity score matching across 2,153 commercial and 787 Medicaid patients.","limitations":"Observational retrospective design. Patients who add GLP-1 drugs may be more health-engaged overall. Cannot establish causation. Limited to 6-month primary analysis window, though 365-day sensitivity analysis showed similar results."},{"rthcId":"RPEP-15068","title":"Sex-specific changes in GLP-1RA trends (2019-2024): Impact of FDA approval of semaglutide (Wegovy) for chronic weight management in the United States.","authors":"Daggolu, Jerusha; Chen, Hua","year":2026,"journal":"Diabetes, obesity & metabolism","doi":"10.1111/dom.70555","pmid":"41669827","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"By January 2024, the female-to-male GLP-1RA utilization rate ratio reached 2.68 for adults (163.06 vs 60.84 per 10,000), with Wegovy showing the largest gap at 4.03:1 (57.86 vs 14.37 per 10,000).","whyItMatters":"Understanding who uses GLP-1 drugs helps identify access disparities and inform public health strategies. The gender gap raises questions about whether men are undertreated for obesity or whether marketing and social factors drive differential uptake.","specificNumbers":"","methodology":"Interrupted time series analysis using 2019-2024 MarketScan commercial claims data, with segmented regression comparing utilization trends 30 months before and 31 months after Wegovy FDA approval.","limitations":"Limited to commercially insured patients; may not reflect Medicaid or uninsured populations. Cannot determine clinical appropriateness of prescribing. Does not capture reasons for the gender gap (patient demand vs provider behavior vs marketing)."},{"rthcId":"RPEP-15069","title":"Anti-virulence peptides: a compromising strategy to treat Staphylococcus aureus chronic wound infection.","authors":"Daher, Riham; Pouget, Cassandra; Lavigne, Jean-Philippe; François, Patrice; Dunyach-Remy, Catherine","year":2026,"journal":"Critical reviews in microbiology, 52(2), 414-432","doi":"10.1080/1040841X.2025.2572800","pmid":"41103102","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Antimicrobial peptides from commensal skin bacteria interfere with the S. aureus Agr quorum-sensing system, inhibiting biofilm development and toxin production as a potential alternative to conventional antibiotics for chronic wound infections.","whyItMatters":"Chronic wound infections with antibiotic-resistant S. aureus are a growing healthcare burden. Anti-virulence peptides that disarm rather than kill bacteria represent a paradigm shift that could reduce resistance development while improving wound healing.","specificNumbers":"","methodology":"Narrative review of literature on commensal bacteria-derived antimicrobial peptides and natural compounds that target S. aureus virulence regulatory systems.","limitations":"Most evidence is from in vitro studies. Clinical stability, safety, and delivery of these peptides to wound sites need further investigation. Anti-virulence approaches may not be sufficient as standalone therapies for severe infections."},{"rthcId":"RPEP-15070","title":"Scorpion venom as a molecular treasure: emerging bioactive compounds and translational therapeutic insights.","authors":"Dahiya, Ritu; Goyal, Kanika; Sharma, Kalicharan; Rawat, Aruna; Sharma, Vinita; Mathur, Pooja","year":2026,"journal":"Archives of toxicology, 100(2), 437-450","doi":"10.1007/s00204-025-04251-5","pmid":"41361124","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Scorpion venom peptides show translational promise across oncology (apoptosis induction, angiogenesis inhibition), neurology (ion channel modulation for pain and arrhythmias), and infectious disease (antimicrobial activity against MDR bacteria).","whyItMatters":"With growing antibiotic resistance and limited options for some cancers and neurological conditions, scorpion venom peptides represent an untapped natural pharmacy that could yield novel therapeutics across multiple disease areas.","specificNumbers":"","methodology":"Comprehensive literature review analyzing studies from 2000-2025 on scorpion venom structural and functional properties, with focus on translational therapeutic potential.","limitations":"Most venom-derived candidates remain at preclinical stages. Toxicity management is a major challenge. Isolation and production at scale remain difficult despite recombinant advances."},{"rthcId":"RPEP-15071","title":"Precision design of an HLA-I-targeted multiepitope vaccine against human papillomavirus 16 oncoproteins E6/E7: integrated immunoinformatic and immunogenicity profiling.","authors":"Dai, Jie; Yang, Rui; Cun, Yina; Zhang, Xinwen; Li, Jing; Shi, Lei; Zhou, Lili; Tao, Yufen; Shi, Li; Yao, Yufeng; Liu, Shuyuan","year":2026,"journal":"Anti-cancer drugs, 37(1), 58-66","doi":"10.1097/CAD.0000000000001790","pmid":"41191800","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Four high-affinity HLA-A*02:01-restricted peptides from HPV16 E6/E7 induced dendritic cell maturation, CD8+ T cell activation and proliferation, and potent antigen-specific cytotoxic T cell responses against tumor cells.","whyItMatters":"HPV causes nearly all cervical cancers and many other cancers. A therapeutic peptide vaccine that can activate the immune system to clear existing HPV infections could prevent cancer progression in millions of already-infected women.","specificNumbers":"","methodology":"Integrated immunoinformatic screening (3 T-cell epitope prediction programs, 5 bioinformatic databases), T2 cell-binding validation, ex vivo CTL induction, and in vivo immunogenicity testing in HLA-A*02:01/H-2Dd transgenic mice.","limitations":"Restricted to HLA-A*02:01 (about half the population). Tested in transgenic mice, not yet in human clinical trials. Efficacy against established tumors in humans may differ from preclinical models. Single HPV type (HPV16) targeted."},{"rthcId":"RPEP-15072","title":"Synthesis of Enduracididine Free Linear Teixobactin Analogs: Molecular Docking, DFT Calculations, and Their Antimicrobial Activities, Bacterial Cell Wall Lysis and Glucose Assay.","authors":"Dalli, Kumari; Sadhanala, Trimurthulu; Govindappa, Nagendra; Kuruvalli, Gouthami; Vaddi, Damodara Reddy; Reddy, Aravinda Thippa; Jayaprakash, Gururaj Kudur","year":2026,"journal":"Current medicinal chemistry","doi":"10.2174/0109298673382051251001045242","pmid":"41540518","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"TX1 and TX3 analogs showed bactericidal activity with inhibition zones of 6.49-11.50 mm at 70-80 μg/mL against four bacterial species, while TX2, TX3, and TX5 showed fungicidal activity (7.23-10.23 mm zones) against A. niger and Fusarium.","whyItMatters":"Teixobactin is considered one of the most promising new antibiotic classes, but its complexity has hindered development. These simplified analogs demonstrate that the core antimicrobial activity can be retained in easier-to-synthesize forms.","specificNumbers":"","methodology":"Solid-phase peptide synthesis of five teixobactin analogs, characterized by mass spectrometry, NMR, and HPLC, with antimicrobial susceptibility testing, cell wall lysis assays, glucose uptake assays, molecular docking, and DFT calculations.","limitations":"In vitro activity only; no animal model testing. Activity at 70-80 μg/mL is relatively high compared to established antibiotics. Pharmacokinetics, toxicity, and stability in vivo are unknown."},{"rthcId":"RPEP-15073","title":"Identification of antihypertensive, antidiabetic, and antioxidant peptides derived from hydrolysates of dairy white wastewaters containing milk proteins using machine learning insights.","authors":"Damen, Diala; Aboubacar, Hairati; Cournoyer, Aurore; Bazinet, Mathieu; de Toro-Martín, Juan; Gaaloul, Sami; Hamoudi, Safia; Cudennec, Benoit; Bazinet, Laurent","year":2026,"journal":"Food research international (Ottawa, Ont.), 229, 118496","doi":"10.1016/j.foodres.2026.118496","pmid":"41763818","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The tripeptide LRF showed ACE inhibitory potency five times greater than captopril (IC50 11.34 μM vs 63.06 μM), while several other peptides demonstrated dual ACE and DPP-IV inhibition with micromolar IC50 values.","whyItMatters":"Finding drug-like peptides in industrial waste transforms a pollution problem into a health resource. These multifunctional peptides could lead to natural alternatives or supplements for managing blood pressure and diabetes.","specificNumbers":"","methodology":"Enzymatic hydrolysis with four enzymes (up to 240 min), LC-MS/MS peptidomics, PLS-DA multivariate statistics, QSAR machine learning scoring, followed by synthesis and experimental validation of 20 selected peptides.","limitations":"In vitro activity only; oral bioavailability and in vivo efficacy not tested. Peptides may be degraded during digestion. Dairy wastewater composition varies by facility, affecting reproducibility. Regulatory pathway for waste-derived bioactive peptides is unclear."},{"rthcId":"RPEP-15074","title":"The Influence of Glucagon-like Peptide-1 Receptor Agonists on Outcomes Following Trigger Finger Release.","authors":"Dameron, Laura S; Bank, Nicholas C; Raghava, Narayan; Himmelberg, Stephen; Knoll, Gregory M","year":2026,"journal":"Journal of hand surgery global online, 8(2), 100923","doi":"10.1016/j.jhsg.2025.100923","pmid":"41657744","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RA exposure was associated with increased scarring (90d: 1.5% vs 0.9%), postoperative pain (90d: 13.2% vs 10.6%), wound complications (90d: 1.7% vs 0.9%), and repeat surgery at 1 year (11.4% vs 9.5%) after trigger finger release.","whyItMatters":"As GLP-1 drugs become ubiquitous, understanding when they may worsen outcomes is as important as knowing when they help. This finding suggests GLP-1 drugs may impair tendon or wound healing in ways relevant to hand surgery.","specificNumbers":"","methodology":"Retrospective propensity-matched cohort study using the TriNetX US Collaborative Network with 4,283 patients per group, comparing GLP-1 RA exposure within 1 year of surgery to no exposure.","limitations":"Retrospective observational design. Cannot establish causation. Patients on GLP-1 drugs may have underlying metabolic conditions affecting healing. Specific GLP-1 agents and doses not differentiated."},{"rthcId":"RPEP-15075","title":"Do GLP-1 Receptor Agonists Alter Brain Responses to Reward-Related Cues? A Systematic Review.","authors":"Dang, Vincent; Sambuco, Nicola; Yammine, Luba; Versace, Francesco","year":2026,"journal":"bioRxiv : the preprint server for biology","doi":"10.64898/2026.01.31.702984","pmid":"41676468","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Only 11 fMRI studies exist on GLP-1 RA effects on brain reward responses. Limited evidence suggests acute administration may reduce food cue reactivity in appetite and reward brain regions, but effects appear inconsistent and may attenuate with chronic treatment.","whyItMatters":"Understanding how GLP-1 drugs affect brain reward circuits is crucial for explaining their weight loss effects and potential for treating substance use disorders like alcohol addiction.","specificNumbers":"","methodology":"Systematic review of 1,209 records from comprehensive literature search, with 11 studies meeting eligibility criteria for analysis of fMRI-measured brain responses to reward cues during GLP-1 RA treatment.","limitations":"Very few eligible studies (11). Small sample sizes throughout. Heterogeneous medications, doses, and protocols. Almost no data on non-food reward cues. No standardized control conditions."},{"rthcId":"RPEP-15076","title":"Glucagon-like peptide-1 receptor agonists after recent burn injury are associated with lower rates of infection, mortality, and opioid prescriptions.","authors":"Dao, Matthew Q; Kim, Anika Y; Wang, Sarah; Won, Paul; Laspro, Matteo; Gillenwater, T Justin; Yenikomshian, Haig A; Johnson, Maxwell B","year":2026,"journal":"Burns : journal of the International Society for Burn Injuries, 52(2), 107848","doi":"10.1016/j.burns.2025.107848","pmid":"41581262","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"At 90 days, GLP-1 RA users had significantly lower rates of soft tissue infection, opioid prescriptions, readmission, and mortality (all p<0.05), with benefits persisting at 1 year for opioids, readmission, and mortality.","whyItMatters":"Burns cause severe inflammation, pain, and high complication rates. If GLP-1 drugs can reduce infections and opioid dependence after burns, they could become an important addition to burn care protocols.","specificNumbers":"","methodology":"Retrospective propensity-matched cohort study using TriNetX electronic health records with 3,231 patients per group matched on demographics, comorbidities, and burn characteristics.","limitations":"Retrospective observational design. Patients on GLP-1 drugs may have better baseline health. Cannot determine if GLP-1 drugs directly caused better outcomes. No significant wound healing improvements (scarring, contractures)."},{"rthcId":"RPEP-15077","title":"Peptide receptor radionuclide therapy: a new era of radiation nephropathy.","authors":"Das, Abhirami; Kendi, Ayse Tuba; Manohar, Sandhya","year":2026,"journal":"Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 41(2), 220-232","doi":"10.1093/ndt/gfaf121","pmid":"40637735","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"PRRT causes radiation nephropathy through renal reabsorption of radiolabeled peptides, with current mitigation strategies including amino acid co-infusion, receptor saturation, and cleavable linker technology showing promise for kidney protection.","whyItMatters":"As PRRT becomes increasingly used for neuroendocrine tumors and other cancers, understanding and preventing kidney damage is essential for patient safety and expanding this effective peptide-based therapy to more patients.","specificNumbers":"","methodology":"Narrative review of PRRT physics, renal handling of radionuclides, nephropathy mechanisms, dose thresholds, and protective strategies, written for practicing nephrologists.","limitations":"Narrative review without new data. Protective strategies vary in evidence level. Many emerging approaches are still preclinical. Individual patient risk prediction remains imprecise."},{"rthcId":"RPEP-15078","title":"Substituent-Based Modulation of Self-Assembly and Immunogenicity of Amphipathic Peptides.","authors":"Das, Anirban; Pramanik, Ushasi; Brown, Elise M; Liu, Chih-Yun; Gong, Huan; Fascetti, Jonathan; Gibson, Mark; Stealey, Samuel; Zustiak, Silviya P; Berkland, Cory; Sharma, Piyoosh; Jackrel, Meredith E; White, Mark A; Rudra, Jai S","year":2026,"journal":"Advanced science (Weinheim, Baden-Wurttemberg, Germany), e18567","doi":"10.1002/advs.202518567","pmid":"41560329","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Substituent modifications at the para-position of benzyl groups on amphipathic peptides produced notable effects on fibril formation, molecular packing, and immunogenicity in both cell culture and animal models.","whyItMatters":"Being able to tune both the physical and immunological properties of self-assembling peptides through simple chemical modifications gives researchers powerful tools for designing the next generation of peptide-based vaccines, tissue scaffolds, and drug delivery systems.","specificNumbers":"","methodology":"Systematic structure-activity study of chemically modified amphipathic peptides, with characterization of self-assembly properties and immunogenicity testing in vitro and in vivo.","limitations":"Limited to short amphipathic peptides with specific aromatic modifications. In vivo immunogenicity was demonstrated but long-term outcomes and therapeutic efficacy not assessed."},{"rthcId":"RPEP-15079","title":"Protein and peptide based nanotherapeutics for the management of Alzheimer's disease: Current insights and future directions.","authors":"Das, Sandeep Kumar; Bashir, Bushra; Kolekar, Kaustubh Ajit; Harish, Vancha; Patle, Deepshikha; Vishwas, Sukriti; Mittal, Neeraj; Jha, Saurabh Kumar; Kumar, Puneet; Gupta, Gaurav; Dureja, Harish; Dua, Kamal; Chang, Dennis; Kuppusamy, Gowthamarajan; Singh, Sachin Kumar","year":2026,"journal":"Ageing research reviews, 114, 103000","doi":"10.1016/j.arr.2025.103000","pmid":"41421725","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Multiple therapeutic peptides (SS31, LPfFFD-PEG, SEN1576, α-sheet peptides, RI-OR2-TAT, TFP5, etc.) show anti-amyloid, anti-tau, and neuroprotective effects, with nanoparticle delivery significantly improving blood-brain barrier penetration and brain accumulation.","whyItMatters":"Alzheimer's affects over 50 million people worldwide. Peptides that can target multiple disease mechanisms simultaneously—when properly delivered to the brain—could provide disease-modifying treatment that current drugs cannot.","specificNumbers":"","methodology":"Comprehensive narrative review of protein and peptide therapeutics for Alzheimer's disease, focusing on nanotechnology-based delivery strategies for crossing the blood-brain barrier.","limitations":"Almost all evidence is preclinical. Blood-brain barrier models in animals don't perfectly predict human crossing. Manufacturing scalable nanoparticle formulations remains challenging. No peptide nanotherapy has reached late-stage clinical trials for AD."},{"rthcId":"RPEP-15080","title":"GLP-1 receptor agonist-associated eosinophilic duodenitis presenting as a bowel obstruction : a case report and literature review.","authors":"Davidts, S; Loumaye, A; Dano, H; Annet, L; Delire, B","year":2026,"journal":"Acta gastro-enterologica Belgica, 89(1), 93-96","doi":"10.51821/89.1.14613","pmid":"41745643","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"First reported case of semaglutide-associated eosinophilic duodenitis causing high bowel obstruction, with endoscopic and histological confirmation of marked eosinophilic infiltration.","whyItMatters":"As millions more people take GLP-1 drugs, recognizing rare but serious GI adverse effects is critical. This case adds eosinophilic gastrointestinal disease to the differential diagnosis for GLP-1 patients with severe GI symptoms.","specificNumbers":"","methodology":"Single case report with endoscopic, histological, and clinical documentation, plus literature review.","limitations":"Single case report—cannot establish causation. The patient may have had pre-existing susceptibility to eosinophilic GI disease. No ability to estimate incidence from a single case."},{"rthcId":"RPEP-15081","title":"A metabolic comparison of GIPR agonism versus GIPR antagonism in male mice.","authors":"Davies, Iona; Turland, Alexandra; Tran, Hanh Duyen; Wong, Carissa; Cahn, Olivier; Dunsterville, Cecilia; Sun, Yichang; Xiao, Yilin; Murphy, Kevin G; Bloom, Stephen R; Jones, Ben; Tan, Tricia M M","year":2026,"journal":"Diabetes, obesity & metabolism, 28(2), 1160-1167","doi":"10.1111/dom.70300","pmid":"41287212","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Both GIPR agonism and antagonism reduced weight via decreased food intake in obese mice, but with distinct metabolic profiles: the agonist improved glucose tolerance independently of weight loss, while the antagonist produced more sustained appetite suppression but reduced insulin sensitivity.","whyItMatters":"Understanding why both activation and blockade of the GIP receptor cause weight loss is crucial for designing optimal next-generation obesity and diabetes drugs. These distinct mechanisms suggest different patients may benefit from different approaches.","specificNumbers":"","methodology":"Preclinical comparison study in lean and diet-induced obese male mice evaluating GIP108 (agonist) vs NN-GIPR-Ant (antagonist) on food intake, body weight, glucose/insulin tolerance, liver triglycerides, bone markers, and adipose gene expression, with pair-fed controls.","limitations":"Male mice only—sex differences in GIP signaling are known. Lean mice showed minimal effects, limiting translatability. Short-term study may miss long-term metabolic consequences. Mouse physiology doesn't perfectly predict human responses."},{"rthcId":"RPEP-15082","title":"How do GLP-1 receptor agonists influence the progression of shoulder pathology? A matched cohort analysis.","authors":"Davis, William R; Bank, Nicholas C; Lauck, Bradley J; Creighton, Robert A; Mistovich, R Justin","year":2026,"journal":"JSES reviews, reports, and techniques, 6(1), 100613","doi":"10.1016/j.xrrt.2025.100613","pmid":"41458332","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1RA use was associated with significantly higher 5-year incidence of adhesive capsulitis (HR up to 2.465), rotator cuff tears, and glenohumeral OA across all subgroups, but lower shoulder fracture risk in obese T2DM patients (HR 0.903).","whyItMatters":"GLP-1 drugs are taken by millions and their effects on musculoskeletal health are poorly understood. These findings suggest potential adverse effects on shoulder soft tissues that clinicians and patients should be aware of.","specificNumbers":"","methodology":"Retrospective cohort study using TriNetX database (2017-2019) with 1:1 propensity score matching across three subgroups, evaluating 5-year shoulder outcomes and 2-year metabolic outcomes.","limitations":"Retrospective observational design. Cannot prove GLP-1 drugs cause shoulder pathology. Patients seeking GLP-1 prescriptions may be more health-aware and thus more likely to report shoulder symptoms. Confounding by indication possible."},{"rthcId":"RPEP-15083","title":"Incretin-Based Therapies: A Novel Pathway in Addiction Treatment.","authors":"Dawid, Rosiejka; Joanna, Michałowska; Justyna, Marcickiewicz; Bogdańska, Adela; Błażejewska, Wiktoria; Szulińska, Monika","year":2026,"journal":"Journal of clinical medicine, 15(4)","doi":"10.3390/jcm15041613","pmid":"41753300","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Preclinical studies consistently demonstrate GLP-1 RAs reduce substance intake, attenuate reward-related behaviors, and suppress relapse-like responding across alcohol, nicotine, opioids, psychostimulants, and cannabinoids.","whyItMatters":"Addiction is a leading cause of death and disability globally, with limited effective pharmacotherapies. GLP-1 drugs are already widely available and could represent a breakthrough treatment if addiction benefits are confirmed in clinical trials.","specificNumbers":"","methodology":"Narrative review of preclinical animal models and human observational studies on incretin-based therapies in addiction across multiple substance classes.","limitations":"Human evidence is largely observational. No published randomized controlled trials for addiction specifically. Animal models may not fully predict human addiction responses. Long-term effects of GLP-1 drugs on brain reward circuits are unknown."},{"rthcId":"RPEP-15084","title":"Synergy between Antimicrobial Peptides and Lipid Nanoparticles for Skin Infection Control.","authors":"de Alcântara Sica de Toledo, Lucas; Rosseto, Hélen Cássia; Buccini, Danieli Fernanda; Franco, Octávio Luiz","year":2026,"journal":"ACS applied materials & interfaces, 18(5), 7740-7754","doi":"10.1021/acsami.5c18033","pmid":"41317099","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"LNP encapsulation of AMPs increases bioavailability, prolongs antimicrobial activity, improves skin penetration, and reduces systemic toxicity, with both solid lipid nanoparticles and nanostructured lipid carriers showing efficacy in vitro and in vivo.","whyItMatters":"Drug-resistant skin infections are a growing public health crisis. AMPs offer a solution but can't be used effectively without proper delivery. LNP technology could be the key to making AMP-based treatments clinically practical.","specificNumbers":"","methodology":"Comprehensive narrative review of AMP encapsulation in lipid nanoparticles, covering mechanisms of action, in vitro/in vivo efficacy, and controlled release strategies for skin infection applications.","limitations":"Most evidence is preclinical. Scalable manufacturing of AMP-loaded LNPs is challenging. Regulatory pathways for these combination products are complex. Long-term skin safety data are limited."},{"rthcId":"RPEP-15085","title":"Muscle health in the modern era of incretin-based therapies.","authors":"De Girolamo, Giuseppe; Sangineto, Moris; Di Gioia, Giuseppe; Bianco, Rossella; Ciarnelli, Martina; Serviddio, Gaetano","year":2026,"journal":"European journal of clinical investigation, 56(1), e70155","doi":"10.1111/eci.70155","pmid":"41328795","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1RA-induced weight loss is predominantly fat mass. Lean body mass declines modestly in absolute terms, but muscle function and strength are preserved, with preclinical evidence suggesting improvements in muscle quality.","whyItMatters":"Millions of people use GLP-1 drugs for weight loss, and muscle loss is one of the biggest safety concerns. This evidence provides reassurance while identifying practical strategies to maintain muscle health.","specificNumbers":"","methodology":"Narrative review of preclinical and clinical evidence on GLP-1 receptor agonists' effects on skeletal muscle tissue, body composition, and physical function.","limitations":"Most studies have relatively short follow-up. Long-term effects on muscle mass and function, especially in elderly patients, need more data. Body composition measurement methods vary across studies."},{"rthcId":"RPEP-15086","title":"Impaired Brain Incretin and Gut Hormone Expression in Human Alcohol-Related Brain Damage: Opportunities for Therapeutic Targeting.","authors":"de la Monte, Suzanne M; Tong, Ming; Carlson, Rolf I; Sutherland, Greg","year":2026,"journal":"Biomolecules, 16(1)","doi":"10.3390/biom16010099","pmid":"41594639","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"AUD reduced GLP-1, GIP, leptin, and ghrelin immunoreactivity in the frontal lobe, while pancreatic polypeptide was reduced in the cerebellar vermis, alongside increased neurodegeneration marker NfL in both regions.","whyItMatters":"If alcohol damages the brain's incretin system, GLP-1 drugs could potentially treat not just the addiction aspects of AUD but also the cognitive and neurobehavioral deficits that make recovery so difficult.","specificNumbers":"","methodology":"Postmortem study comparing cerebellar vermis and anterior frontal lobe tissue from 6 adult male AUD donors and 6 controls using duplex and multiplex ELISAs for NfL and gut hormone panel.","limitations":"Very small sample size (6 per group). Male subjects only. Postmortem tissue analysis cannot determine causality or temporal relationships. Cannot distinguish effects of alcohol from effects of nutritional deficiency common in AUD."},{"rthcId":"RPEP-15087","title":"Efficacy and Safety of Pharmacological, Endoscopic, and Surgical Treatments for Obesity: A GRADE-Based Network Meta-Analysis.","authors":"De Luca, Maurizio; Cohen, Ricardo V; Belluzzi, Amanda; Navarra, Giuseppe; Di Lorenzo, Nicola; Petry, Tarissa B Z; Sbraccia, Paolo; Busetto, Luca; Buscemi, Silvio; Barazzoni, Rocco; Ragghianti, Benedetta; Mannucci, Edoardo; Monami, Matteo","year":2026,"journal":"Obesity (Silver Spring, Md.), 34(2), 279-293","doi":"10.1002/oby.70083","pmid":"41539943","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"At 26-52 weeks, tirzepatide achieved >10% TBWL comparable to most surgeries. Long-term, surgical procedures (RYGB, SG, SADI, BPD) remained superior. Semaglutide and tirzepatide showed no inferior short-term results vs MBS.","whyItMatters":"This is the most comprehensive comparison of all obesity treatments to date, directly informing clinical decisions about when to recommend medications versus procedures for different patients.","specificNumbers":"","methodology":"GRADE-based network meta-analysis of 139 RCTs (54 MBS, 21 EBP, 64 OMM) analyzing total body weight loss percentage at four timepoints up to 3+ years, registered in PROSPERO.","limitations":"Long-term data lacking for most medications and all endoscopic procedures. Indirect comparisons through network meta-analysis have inherent limitations. Studies varied in patient populations and follow-up methods."},{"rthcId":"RPEP-15088","title":"Effect of GLP-1 receptor agonists on idiopathic intracranial hypertension: A systematic review.","authors":"de Oliveira, Helen Michaela; Gallo Ruelas, Mariano; Fonseca, Pandora Eloa Oliveira; Diaz, Camilo André Viana; de Paula, Guilherme Oliveira; da Costa, Pablo Ramon Fruett; Parker, Tariq; Kahle, Kristopher T","year":2026,"journal":"Headache, 66(1), 286-297","doi":"10.1111/head.70005","pmid":"41246926","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 12 studies (3 RCTs, 6 retrospective cohorts, 1 case-control, 2 case reports), GLP-1 RAs generally improved papilledema and headache burden in IIH, with no cognitive harm, but visual outcomes and intracranial pressure data were inconsistent.","whyItMatters":"IIH predominantly affects young overweight women and can cause permanent vision loss. If GLP-1 drugs can treat this condition by reducing brain pressure and weight simultaneously, they could offer a much-needed therapeutic option.","specificNumbers":"","methodology":"Systematic review of 5 databases with 12 eligible studies, using RoB 2, ROBINS-I/E, and JBI tools for bias assessment. Narrative synthesis due to heterogeneity precluding meta-analysis. Registered in PROSPERO.","limitations":"Low evidence certainty. Mostly observational studies with short follow-up. Small sample sizes. No standardized outcome definitions. Database analyses may have selection bias."},{"rthcId":"RPEP-15089","title":"Cardio-Obesity and Therapeutic Advances: Intersections Between Excess Adiposity, Cardiovascular Risk, and Pharmacologic Interventions.","authors":"De Oliveira-Gomes, Diana; de Majo, Alfonso Martinez; Ardila-Delgado, Angie; Inglis, Sara S; Mandras, Stacy A; Loro-Ferrer, Juan F; daSilva-deAbreu, Adrian","year":2026,"journal":"Current atherosclerosis reports, 28(1), 21","doi":"10.1007/s11883-026-01395-2","pmid":"41686329","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Incretin agonists reduce body weight by 10-20% and significantly lower major adverse cardiovascular events (cardiovascular death, nonfatal MI, stroke) in patients with and without diabetes, with benefits extending beyond glycemic control.","whyItMatters":"Obesity-related cardiovascular disease is the leading cause of death worldwide. The dual metabolic and cardiovascular benefits of incretin drugs position them as transformative treatments that address both root causes.","specificNumbers":"","methodology":"Narrative review of mechanistic pathways linking obesity to cardiovascular disease and clinical trial evidence for pharmacologic therapies including incretin agonists.","limitations":"Narrative review without new data. Long-term cardiovascular outcomes beyond trial durations are unknown. Cost and access remain barriers. Not all patients respond equally."},{"rthcId":"RPEP-15090","title":"Heterologous expression and functional characterization of novel microcin B17 congeners from environmental Pseudomonas isolates.","authors":"De Smedt, Sandrien; Wéry, Dries; Vande Capelle, Hanne; Gerstmans, Hans; Monsieurs, Pieter; Masschelein, Joleen; Ruelens, Philip; Fauvart, Maarten; Michiels, Jan","year":2026,"journal":"Applied microbiology and biotechnology, 110(1), 45","doi":"10.1007/s00253-025-13698-6","pmid":"41612043","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Four MccB17-like BGCs from Pseudomonas produced modified peptides that caused growth retardation and cell elongation in E. coli, with transcriptomics revealing congener-specific stress responses despite structural similarity.","whyItMatters":"Expanding the diversity of known antibiotic peptides beyond well-studied species could yield new antimicrobial leads. The finding that similar peptides trigger different responses highlights untapped functional diversity in natural peptide antibiotics.","specificNumbers":"","methodology":"Genome mining for BGC identification, heterologous expression in E. coli, RT-qPCR and LC-MS confirmation of peptide production, overlay antimicrobial assays, and RNA-Seq transcriptome profiling.","limitations":"No detectable antibacterial activity in standard overlay assays—the peptides' biological activity may be subtler or require different test conditions. Only expressed in E. coli as a heterologous host. Environmental relevance of these peptides is unknown."},{"rthcId":"RPEP-15091","title":"The effect of combining surgical or endoscopic bariatric interventions with anti-obesity medication or probiotics on weight loss: a narrative review.","authors":"de Waal, J R; Nieuwdorp, M; Gerdes, V E A","year":2026,"journal":"Frontiers in endocrinology, 17, 1680182","doi":"10.3389/fendo.2026.1680182","pmid":"41717546","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RAs combined with ESG produced more weight loss than ESG alone. In post-bariatric weight regain, GLP-1 RAs and tirzepatide showed clinically relevant short-term weight loss, while non-GLP-1 medications and probiotics showed modest or inconsistent effects.","whyItMatters":"Weight regain after bariatric surgery is common and demoralizing. Having effective pharmacological options like GLP-1 drugs to augment surgical results could improve long-term outcomes for millions of bariatric surgery patients.","specificNumbers":"","methodology":"Narrative review of studies combining surgical or endoscopic bariatric interventions with anti-obesity medications or probiotics, focusing on weight loss outcomes.","limitations":"Mostly short-term data. Studies are generally small. No standardized protocols for combining medications with surgery. Long-term safety and efficacy of combination approaches unknown."},{"rthcId":"RPEP-15092","title":"Effects of glucagon-like peptide-1 receptor agonists on male reproductive hormones, semen parameters, and metabolic outcomes: a systematic review.","authors":"Deameh, Mohammad Ghassab; Ramez, Mohamed; Rowaiee, Rashed; Bani Irshid, Baha' Aldeen; Mohamed, Hamza; Abdelshafi, Abdelrahman; Al-Osoufi, Mohammad Ali; Mohamed, Tarek; Hegazin, Safa Botros; Raheem, Omer","year":2026,"journal":"The journal of sexual medicine, 23(2)","doi":"10.1093/jsxmed/qdaf381","pmid":"41498523","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1RAs consistently increased total testosterone in men with metabolic dysfunction while preserving or increasing LH and FSH levels, in contrast to testosterone therapy which suppresses gonadotropins and fertility.","whyItMatters":"Many men with obesity have low testosterone and want treatment, but testosterone replacement suppresses fertility. GLP-1 drugs could offer both metabolic and reproductive benefits without compromising sperm production.","specificNumbers":"","methodology":"Systematic review following PRISMA guidelines, searching 4 databases through April 2025, including RCTs and cohort studies with risk of bias assessment using RoB 2 and ROBINS-I tools.","limitations":"Relatively few studies with small sample sizes. Free testosterone changes were inconsistent. No long-term fertility outcomes measured. Most evidence from men with metabolic conditions."},{"rthcId":"RPEP-15093","title":"A Cross-Sectional Study on Elevated Serum Calcitonin Gene-Related Peptide Levels in Rheumatoid Arthritis Patients and Their Relationship with Disease Activity.","authors":"Dede Akpınar, Merve; Ataoğlu, Safinaz; Cangür, Şengül","year":2026,"journal":"Archives of rheumatology, 41(1), 29-39","doi":"10.5152/ArchRheumatol.2026.10704","pmid":"41618493","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Serum CGRP was significantly elevated in RA (91.1 vs 40.8 pg/mL, p<0.001), with seropositive patients showing higher levels (118.7 pg/mL). CGRP correlated with DAS-28, HAQ, and VAS scores and was an independent predictor of active disease.","whyItMatters":"CGRP is already targeted by migraine drugs (anti-CGRP antibodies). Finding it elevated in RA opens the question of whether these same drugs could help manage rheumatoid arthritis pain and inflammation.","specificNumbers":"","methodology":"Cross-sectional case-control study with 80 RA patients and 40 healthy controls, using ELISA for CGRP measurement, ROC analysis for diagnostic cutoffs, and logistic regression for predictor analysis.","limitations":"Cross-sectional design cannot establish causation. Moderate sample size. Cannot determine if elevated CGRP drives disease or results from it. Single-center study."},{"rthcId":"RPEP-15094","title":"The Association of Neuropeptide Y with the Presence and Frequency of Ventricular Premature Beats.","authors":"Dedeoglu, Necip Fazıl; Tascanov, Mustafa Begenc; Toprak, Kenan; Fedai, Halil; Bicer, Asuman; Altiparmak, İbrahim Halil; Tanriverdi, Zulkif; Demirbag, Recep; Koyuncu, Ismail","year":2026,"journal":"Current cardiology reviews, 22(1), e1573403X361970","doi":"10.2174/011573403X361970250507035931","pmid":"40377159","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"NPY was an independent predictor of VES (OR 1.204, p=0.001). NPY ≥47.9 ng/L predicted VES with 82% sensitivity and 81.4% specificity; ≥79.8 ng/L predicted high-frequency VES with 85.5% sensitivity and 87.3% specificity.","whyItMatters":"Identifying NPY as a predictor of VES could lead to new therapeutic targets for heart rhythm disorders, as NPY is a neuropeptide that can be pharmacologically modulated.","specificNumbers":"","methodology":"Case-control study with 150 VES patients (48 with >15,000 VES and 102 with <15,000) and 86 controls, using 24-hour Holter monitoring, blood biochemistry, and NPY measurement.","limitations":"Single-center study. Cross-sectional design limits causal inference. Cannot determine if elevated NPY causes VES or results from the same underlying autonomic dysfunction. No intervention tested."},{"rthcId":"RPEP-15095","title":"Deciphering antimicrobial peptide (AMP) resistance mechanisms in Enterococcus faecalis through integrated RNA-Seq and hub genes identification.","authors":"Deepika, J; Shetty, Aishwarya C; T, DhanushKumar; Vasudevan, Karthick","year":2026,"journal":"Advances in protein chemistry and structural biology, 149, 353-374","doi":"10.1016/bs.apcsb.2024.11.014","pmid":"41581937","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Ten hub genes (guaA, guaB, lepA, der, secA, ftsH, obg, nusG, dnaA, ffh) were significantly upregulated in E. faecalis in response to teixobactin, revealing resistance mechanisms spanning metabolism, protein export, and stress response.","whyItMatters":"Teixobactin was thought to be nearly resistance-proof. Understanding resistance mechanisms helps researchers design next-generation AMPs that circumvent these defenses.","specificNumbers":"","methodology":"Whole transcriptome RNA-Seq analysis of teixobactin-exposed Enterococcus faecalis, with bioinformatics identification of central hub genes and pathway analysis.","limitations":"Gene expression changes don't necessarily translate to functional resistance. In vitro exposure conditions may not reflect in vivo scenarios. Single bacterial species studied."},{"rthcId":"RPEP-15096","title":"Pros and Cons of Early Treatment with GLP-1 Receptor Agonist and SGLT-2 Inhibitors for Youth with Type 2 Diabetes: A Narrative Review.","authors":"DeLacey, Sean E; Dieguez, Abigayil C; Bensignor, Megan O","year":2026,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 17(1), 41-54","doi":"10.1007/s13300-025-01823-7","pmid":"41252112","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Standard metformin+insulin therapy fails to prevent complications in most youth T2D patients (cumulative incidence of at least one complication within 13 years). GLP-1RAs and SGLT-2is offer β-cell preservation and weight management benefits that could improve long-term outcomes if used early.","whyItMatters":"Youth-onset T2D is a growing epidemic with devastating long-term consequences. If GLP-1 drugs can preserve beta-cell function when started early, they could prevent decades of diabetes complications in young patients.","specificNumbers":"","methodology":"Narrative review of current evidence for GLP-1 RAs and SGLT-2 inhibitors in youth-onset T2D, focusing on early disease intervention within 1-2 years of diagnosis.","limitations":"Limited long-term data for GLP-1RAs in youth populations. Most evidence extrapolated from adult trials. Optimal timing and combination strategies not yet defined."},{"rthcId":"RPEP-15097","title":"Overlapping pathways of migraine and the endocannabinoid system: Potential therapeutic targets.","authors":"Della Pietra, Adriana; Russo, Andrew F","year":2026,"journal":"Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, e00833","doi":"10.1016/j.neurot.2026.e00833","pmid":"41549028","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The ECS modulates CGRP release and trigeminovascular signaling through TRPV1, D2 dopamine receptors, serotonergic, and ion channel pathways, offering multi-target therapeutic opportunities for CGRP-resistant migraine.","whyItMatters":"Up to 40-50% of migraine patients don't adequately respond to anti-CGRP therapies. Understanding how the ECS interacts with CGRP pathways could lead to new treatments for these patients.","specificNumbers":"","methodology":"Comprehensive narrative review mapping endocannabinoid component distribution in migraine-relevant brain regions and summarizing preclinical evidence for anti-nociceptive effects.","limitations":"Preclinical evidence only; human translational data are very limited. Multi-target compounds add complexity and potential side effects. ECS modulation carries regulatory challenges."},{"rthcId":"RPEP-15098","title":"Processing-induced structural remodeling enhances the hypoglycemic activity of Polygonatum cyrtonema Hua polysaccharides via gut microbiota-SCFA-GPR41/43 pathway.","authors":"Deng, Chuyao; Zheng, Jiaxin; Xu, Fei; Hong, Fengyi; Zhan, Minmin; Chen, Qi; Peng, Ye; Cao, Yong; Xiao, Jie; Liao, Yongcheng; Xiao, Hang; Song, Mingyue","year":2026,"journal":"Food research international (Ottawa, Ont.), 229, 118492","doi":"10.1016/j.foodres.2026.118492","pmid":"41763814","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Processed Polygonatum polysaccharides outperformed raw forms in reducing blood sugar by modulating gut microbiota, increasing SCFA production, upregulating GPR41/43, and boosting endogenous GLP-1 and PYY secretion in diabetic mice.","whyItMatters":"Understanding how dietary compounds boost natural GLP-1 secretion could provide adjunctive approaches to managing diabetes, potentially complementing or reducing the need for synthetic GLP-1 drugs.","specificNumbers":"","methodology":"Enzyme-assisted extraction, structural characterization (MW, monosaccharide, FT-IR, NMR, methylation), and in vivo antidiabetic testing in high-fat diet/streptozotocin-induced T2DM mice with gut microbiota and pathway analysis.","limitations":"Mouse model only; human GI conditions differ significantly. Dosing and bioavailability in humans unknown. The complex polysaccharide compositions may vary by plant source and processing method."},{"rthcId":"RPEP-15099","title":"A hedgehog cathelicidin-derived peptide exhibits antiviral activity against herpes simplex virus type 1 infection.","authors":"Deng, Enjie; Pei, Yaping; Yuan, Kun; Yang, Juan; Cao, Suncheng-Ai; Yang, Xinyan; Li, Guilan; Liang, Libin; Jin, Lin; Zhu, Tengyu","year":2026,"journal":"Frontiers in microbiology, 17, 1770133","doi":"10.3389/fmicb.2026.1770133","pmid":"41788323","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CathEE-2a displayed strong antiviral activity in vitro and significantly reduced HSV-1 brain viral loads in a mouse infection model through upregulation of type I interferons and downstream antiviral genes.","whyItMatters":"HSV-1 infects over 3.7 billion people globally. An immunomodulatory antiviral peptide that boosts natural defenses could complement existing antivirals and address drug-resistant strains.","specificNumbers":"","methodology":"Peptide design from hedgehog cathelicidin, in vitro antiviral testing against HSV-1, in vivo mouse HSV-1 infection model with brain viral load quantification and histopathological analysis.","limitations":"Mouse model only. Specific dosing, pharmacokinetics, and toxicity profile not fully characterized. Only tested against HSV-1; activity against other herpesviruses unknown."},{"rthcId":"RPEP-15100","title":"Effect of Weight-Neutral Treatment With Semaglutide or Tirzepatide on β-Cell Identity in db/db Mice.","authors":"Deng, Zhaobin; Zheng, Dongxu; Son, Jinsook; Du, Wen; McKimpson, Wendy M; Liu, Qingli; Accili, Domenico","year":2026,"journal":"Acta physiologica (Oxford, England), 242(1), e70141","doi":"10.1111/apha.70141","pmid":"41354136","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Both semaglutide and tirzepatide provided comparable glucose lowering and insulin increases after 4 weeks, but neither reversed beta-cell dedifferentiation as measured by ALDH1A3 expression, FOXO1 translocation, or PDX1 levels.","whyItMatters":"Understanding that GLP-1 drugs don't reverse beta-cell dedifferentiation in this timeframe tempers expectations while highlighting that their metabolic benefits must come through other important pathways.","specificNumbers":"","methodology":"Four-week treatment study in 12-week-old db/db mice with oral glucose tolerance testing, immunofluorescence for beta-cell identity markers, and bulk RNA sequencing from islets.","limitations":"Short treatment duration (4 weeks) may be insufficient for dedifferentiation reversal. Single mouse model (db/db). Doses chosen resulted in weight neutrality for semaglutide, which may not reflect optimal dosing. Human beta-cell biology may differ."},{"rthcId":"RPEP-15101","title":"Therapeutic efficacy of synthetic analogues of gut hormones in a mouse model of Alzheimer's disease.","authors":"Denver, Paul; Duffy, Aisling; Kennedy, Rebecca T; Gault, Victor A; McClean, Paula L","year":2026,"journal":"Neuroscience, 600, 63-81","doi":"10.1016/j.neuroscience.2026.01.038","pmid":"41616952","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"All three gut hormone analogues (GLP-1, GIP, xenin-25) reduced amyloid burden and restored synaptophysin levels, with liraglutide and GIP analogue improving cognition, and xenin-25 uniquely increasing neurogenesis.","whyItMatters":"Current Alzheimer's treatments offer minimal benefit. The finding that three different gut hormone peptides each reduce Alzheimer's pathology through overlapping and complementary mechanisms supports a multi-peptide therapeutic strategy.","specificNumbers":"","methodology":"8-10 week treatment study in APP/PS1 transgenic Alzheimer's mice with novel object recognition and Morris water maze testing, immunohistochemistry for amyloid/glia/synapses/neurogenesis, and AD-associated gene expression analysis.","limitations":"Mouse model only. APP/PS1 mice don't fully replicate human Alzheimer's. Relatively short treatment period. Long-acting analogues may behave differently in humans."},{"rthcId":"RPEP-15102","title":"An Unusual Ring Pattern in the Rosβ Lanthipeptide of the Two-Component Lantibiotic Roseocin.","authors":"Desormeaux, Emily K; Zhu, Lingyang; Luo, Youran; Sareen, Dipti; van der Donk, Wilfred A","year":2026,"journal":"Journal of natural products, 89(2), 519-527","doi":"10.1021/acs.jnatprod.5c01339","pmid":"41684297","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Rosβ has a unique ring pattern among characterized lanthipeptides, with six thioether cross-links (lanthionine and methyllanthionine residues) formed by the RosM synthetase from nine dehydrated residues.","whyItMatters":"Understanding the complete structure of novel antimicrobial peptides is essential for elucidating their mechanism of action and developing them as potential antibiotics.","specificNumbers":"","methodology":"Heterologous expression in E. coli, purification, multidimensional NMR spectroscopy for ring pattern determination, and Marfey's analysis with authentic standards for stereochemistry.","limitations":"Structural determination only—no functional activity assays performed in this study. The structure was determined from recombinant expression, which may differ subtly from native production."},{"rthcId":"RPEP-15103","title":"Molecular engineering of designer diabetes therapeutics.","authors":"DeWolf, Emily L; Webber, Bernice; Webber, Matthew J","year":2026,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 392, 114705","doi":"10.1016/j.jconrel.2026.114705","pmid":"41662883","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Core molecular engineering strategies—sequence modifications, formulation-based depot formation, and vascular binding—enable the diverse pharmacokinetic profiles needed across insulin, glucagon, amylin, and GLP-1 therapeutics for diabetes.","whyItMatters":"Diabetes peptide drugs are used by hundreds of millions of people. Understanding the engineering principles behind them informs the development of next-generation therapeutics with better efficacy, convenience, and safety.","specificNumbers":"","methodology":"Comprehensive narrative review of molecular design principles across all major classes of diabetes peptide therapeutics, from structural modifications to delivery systems and glucose-responsive technologies.","limitations":"Review covers broad territory without depth on individual compounds. Some technologies discussed are still early-stage. Not all engineering strategies translate from concept to clinical success."},{"rthcId":"RPEP-15104","title":"GLP-1 Receptor Agonist-Associated Slimmer's Palsy: Implications for the Peripheral Nerve Surgeon.","authors":"Dhupati, Pooja; Kisiel, Sara C; Unadkat, Krishna; Noland, Shelley S","year":2026,"journal":"Annals of plastic surgery, 96(1), 69-74","doi":"10.1097/SAP.0000000000004570","pmid":"41417708","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Two non-diabetic patients developed common peroneal neuropathy (foot drop) after losing 14% and 18% of body weight over 3-6 months on semaglutide and tirzepatide, respectively.","whyItMatters":"With millions of people rapidly losing weight on GLP-1 drugs, peripheral nerve complications may become increasingly common. Early recognition and intervention can prevent permanent nerve damage.","specificNumbers":"","methodology":"Case report of two patients with clinical, electrodiagnostic, and imaging documentation of peroneal nerve injury after GLP-1 RA-induced weight loss.","limitations":"Only two cases reported; cannot estimate incidence. Both patients were non-diabetic; diabetic patients may have different risk profiles due to pre-existing neuropathy."},{"rthcId":"RPEP-15105","title":"Peptide receptor radionuclide therapy alone or in combination with temozolomide plus/minus capecitabine in [18F]FDG-positive metastatic neuroendocrine tumors.","authors":"di Santo, Gianpaolo; Santo, Giulia; Wirth, Lukas; Kronthaler, Ariane; Gastl, Günther; Djanani, Angela; Virgolini, Irene J","year":2026,"journal":"European journal of nuclear medicine and molecular imaging, 53(3), 1927-1938","doi":"10.1007/s00259-025-07606-3","pmid":"41117982","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"PRRT + CAPTEM achieved 71% ORR and DCR in FDG-positive mNETs, compared to 10% ORR/50% DCR for PRRT alone and 14% ORR/43% DCR for PRRT + temozolomide, without increased toxicity.","whyItMatters":"FDG-positive neuroendocrine tumors have poor prognosis with standard PRRT. This combination approach could significantly improve outcomes for these aggressive cancers.","specificNumbers":"","methodology":"Retrospective single-center study of 24 FDG-positive mNET patients receiving PRRT alone (n=10), PRRT+TEM (n=7), or PRRT+CAPTEM (n=7), with response assessment by CT, Ga-68-DOTATOC PET, and FDG PET.","limitations":"Small sample size (24 total, 7 per CAPTEM group). Retrospective design. Single center. Cannot control for selection bias between groups. Survival outcomes need longer follow-up."},{"rthcId":"RPEP-15106","title":"Thymosin beta 4: An emerging therapeutic candidate for kidney diseases.","authors":"Di, Huajie; Huang, Jiaxin; Zhang, Dexin; Ni, Fei; Zheng, Rui; Geng, Hongquan","year":2026,"journal":"Peptides, 195, 171467","doi":"10.1016/j.peptides.2026.171467","pmid":"41570941","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tβ4 and Ac-SDKP demonstrate cytoprotective, anti-inflammatory, and antifibrotic effects across acute and chronic kidney injury models, but with bidirectional effects on fibrosis that depend on context and model.","whyItMatters":"Kidney disease affects hundreds of millions globally with limited treatment options. A naturally occurring peptide that protects kidney cells and reduces scarring could address this massive unmet medical need.","specificNumbers":"","methodology":"Comprehensive narrative review synthesizing evidence on Tβ4-Ac-SDKP axis mechanisms, cell-type expression, signaling pathways, and efficacy across kidney disease models.","limitations":"Bidirectional effects on fibrosis complicate therapeutic application. Most evidence is from animal models. Peptide instability and rapid degradation pose delivery challenges. Comprehensive safety data lacking."},{"rthcId":"RPEP-15107","title":"Kori-tofu ameliorates obesity and steatotic liver disease through enhancing GLP-1 production in the ileum.","authors":"Diao, Pan; Zhang, Xuguang; Ishiguro, Takahiro; Wang, Xiaojing; Tanabe, Kazuhiro; Hayashi, Chihiro; Kittaka, Hiroki; Imamura, Hitomi; Nakajima, Tomoyuki; Zhang, Zhe; Wang, Yaping; Nakajima, Takero; Kimura, Takefumi; Kawakubo, Masatomo; Nakayama, Jun; Nakamuta, Makoto; Tanaka, Naoki","year":2026,"journal":"International journal of biological macromolecules, 341(Pt 2), 149537","doi":"10.1016/j.ijbiomac.2025.149537","pmid":"41360246","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Kori-tofu protein and its resistant protein fraction promoted ileal GLP-1 production via CREB phosphorylation and raised circulating GLP-1 levels, while reducing adipocyte size, inflammation, and hepatic steatosis in HFD-fed mice.","whyItMatters":"Finding natural food compounds that boost endogenous GLP-1 production provides dietary strategies that could complement pharmaceutical GLP-1 therapy for obesity management.","specificNumbers":"","methodology":"16-week feeding study in C57BL/6J mice on high-fat diet with 10% kori-tofu protein or 3% resistant protein, assessing metabolic markers, gene expression, and metabolomics.","limitations":"Mouse model only. Human GI processing of kori-tofu may differ. The amount of protein used (10%) is substantial relative to diet. Azelaic acid-GLP-1 connection is correlative."},{"rthcId":"RPEP-15108","title":"Potential therapeutic role of calcitonin gene-related peptide medications for tinnitus.","authors":"Dichter, Abigail; Bhatt, Khushi; Gutiérrez Pérez, Martha Lucía; Lee, Ella J; Tawk, Karen; Djalilian, Hamid R","year":2026,"journal":"Journal of the Chinese Medical Association : JCMA","doi":"10.1097/JCMA.0000000000001351","pmid":"41612541","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CGRP is involved in both migraine and tinnitus through overlapping neural pathways (auditory and trigeminal), and anti-CGRP medications may offer therapeutic benefit for tinnitus through the same mechanisms that make them effective for migraine.","whyItMatters":"Tinnitus affects 10-15% of the population with very limited treatment options. If anti-CGRP drugs can help, millions of tinnitus sufferers could benefit from medications already available.","specificNumbers":"","methodology":"Narrative review of CGRP's role in migraine and tinnitus pathophysiology, with focus on shared neurological pathways and therapeutic implications.","limitations":"Narrative review with no clinical trial data for anti-CGRP drugs in tinnitus. The overlap between migraine and tinnitus mechanisms, while plausible, needs experimental confirmation. CGRP's specific role in tinnitus is not fully characterized."},{"rthcId":"RPEP-15109","title":"Drugs for Migraine Prophylaxis.","authors":"Diener, Hans Christoph; Grans, Julia; Reuter, Uwe","year":2026,"journal":"Deutsches Arzteblatt international","doi":"10.3238/arztebl.m2025.0234","pmid":"41572863","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Anti-CGRP antibodies reduce migraine days by 0.7-3.8/month and atogepant by 0.7-2.4/month, with efficacy maintained in patients refractory to traditional oral prophylactics.","whyItMatters":"Migraine affects over 1 billion people globally. Anti-CGRP drugs represent the first migraine-specific preventive therapy class and help patients who don't respond to older medications.","specificNumbers":"","methodology":"Narrative review based on International Headache Society guidelines with additional meta-analyses of anti-CGRP monoclonal antibodies and gepants.","limitations":"Efficacy data from clinical trials may not fully reflect real-world effectiveness. Head-to-head comparisons between anti-CGRP agents are limited. Long-term safety data still accumulating. Cost remains a barrier for many patients."},{"rthcId":"RPEP-15110","title":"Honey Bee AMPs as a Novel Carrier Protein for the Development of a Subunit Vaccine: An Immunoinformatic Approach.","authors":"Dinata, Roy; Baindara, Piyush; Arati, Chettri; Gurusubramanian, Guruswami","year":2026,"journal":"Current issues in molecular biology, 48(1)","doi":"10.3390/cimb48010081","pmid":"41614911","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Five bee AMPs (P15450, A0A2A3EK62, Q86BU7, C7AHW3, I3RJI9A) showed high antigenicity, non-allergenic profiles, and stable binding to TLR3 and TLR4-MD2 receptors through molecular dynamics simulations.","whyItMatters":"Effective vaccines against drug-resistant pathogens need strong adjuvants and carrier molecules. Bee-derived AMPs could provide natural, biocompatible options that both stimulate immunity and carry vaccine antigens.","specificNumbers":"","methodology":"Immunoinformatics screening of 82 BAMPs from 7 families across 8 bee species, structural modeling, molecular docking with TLR3/TLR4-MD2, molecular dynamics simulations, and in silico immune simulations.","limitations":"Entirely computational study; no experimental validation of immunogenicity. In silico immune simulations may not predict real-world vaccine responses. Manufacturing feasibility not addressed."},{"rthcId":"RPEP-15111","title":"NGR-modified cancer-associated fibroblast-derived exosomes deliver resveratrol to inhibit CXCR2/NF-κB signaling in myeloid-derived suppressor cells and reverse immune suppression in liver cancer.","authors":"Ding, Lijuan; Wang, Qiang; Wang, Xue; Fu, Weijia; Deng, Chen; Wang, Shudong","year":2026,"journal":"International immunopharmacology, 174, 116326","doi":"10.1016/j.intimp.2026.116326","pmid":"41679176","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"NGR-peptide-modified exosomes loaded with resveratrol achieved 19.3% drug encapsulation efficiency, targeted tumor MDSCs, downregulated CXCR2/NF-κB signaling, and significantly reduced tumor volume while boosting CD8+ T cell activity in a liver cancer model.","whyItMatters":"Immunotherapy resistance is often driven by immunosuppressive cells in the tumor. This peptide-guided exosome platform offers a way to reverse that suppression and restore anti-tumor immunity.","specificNumbers":"","methodology":"Network pharmacology, single-cell RNA-seq analysis, generation of CAF-derived NGR-modified exosomes, in vitro MDSC/T cell co-culture assays, and in vivo murine liver cancer xenograft model.","limitations":"Mouse xenograft model only. Exosome manufacturing scalability is challenging. Long-term safety of CAF-derived exosomes unknown. Applicability to other cancer types not tested."},{"rthcId":"RPEP-15112","title":"An in vivo study of the antihypertensive effects of the umami peptide AHSVRFY from Parma ham and its intestinal digestion.","authors":"Ding, Qian; Wang, Tianyu; Dang, Kuo; Wang, Yanli; Pan, Daodong; Xia, Qiang; Gao, Xinchang; Dang, Yali","year":2026,"journal":"Food & function, 17(1), 315-328","doi":"10.1039/d5fo03304g","pmid":"41351565","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Oral AHSVRFY reduced SBP by 13.9 ± 2.7 mmHg in SHRs through its GI-released dipeptide FY (ACE IC50 = 45.11 μM), which was absorbed intact and improved vascular endothelial function via NO/ET-1 modulation.","whyItMatters":"Validates a \"digestion-activation-delivery\" framework showing that food peptides can be designed to release active fragments during digestion, bridging food science and pharmaceutical development.","specificNumbers":"","methodology":"Oral dosing in spontaneously hypertensive rats with blood pressure monitoring, simulated GI digestion, plasma peptide identification, endothelial cell (HUVEC) assays, and molecular docking/dynamics simulations.","limitations":"Rat model; human blood pressure effects may differ. Single-dose study; chronic effects unknown. The 13.9 mmHg reduction in rats may not translate proportionally to humans."},{"rthcId":"RPEP-15113","title":"GLP-1 receptor agonists and acute pancreatitis: fact or overstated risk?","authors":"Domínguez Muñoz, Juan Enrique; Lariño Noia, José; Domínguez Novoa, Yessica; Iglesias-García, Julio","year":2026,"journal":"Revista espanola de enfermedades digestivas, 118(1), 64-65","doi":"10.17235/reed.2025.11499/2025","pmid":"41020937","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GI adverse effects affect up to 80% of GLP-1 RA users in a dose-dependent manner, but the association with acute pancreatitis remains uncertain and may be overstated based on current pharmacovigilance and clinical trial evidence.","whyItMatters":"The pancreatitis concern has been a significant barrier to GLP-1 drug prescribing. Clarifying this risk helps patients and clinicians make informed decisions about these widely used medications.","specificNumbers":"","methodology":"Narrative review of clinical trial data and pharmacovigilance reports on GLP-1 RA gastrointestinal safety, with focus on the pancreatitis question.","limitations":"Narrative review without systematic analysis. Pancreatitis is rare, making it difficult to study definitively in clinical trials. Post-marketing surveillance has inherent biases."},{"rthcId":"RPEP-15114","title":"Modulation of LPS-associated virulence activity for reduction of periodontal inflammatory burden.","authors":"Dong, Anbo; Lehto, Markku; Putaala, Jukka; Paju, Susanna; Pussinen, Pirkko; Zaric, Svetislav","year":2026,"journal":"Frontiers in microbiology, 17, 1728315","doi":"10.3389/fmicb.2026.1728315","pmid":"41695955","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"LL-37 and polymyxin B reduced endotoxin activity in oral biofilms by >90% and decreased pro-inflammatory cytokine secretion by 40-75% while preserving anti-inflammatory cytokines, with LL-37 showing stronger IRF pathway inhibition.","whyItMatters":"Periodontal disease affects nearly half of adults. An approach that neutralizes bacterial toxins rather than killing all bacteria could provide targeted treatment that preserves the beneficial oral microbiome.","specificNumbers":"","methodology":"Endotoxin measurement (rFC assay) and immune stimulation assays (THP-1 and THP-1 Dual cells, NF-κB/IRF pathway assessment, cytokine profiling) using saliva and subgingival biofilm from 324 participants (healthy, gingivitis, periodontitis).","limitations":"In vitro study only. Clinical feasibility of delivering LL-37 to periodontal pockets not addressed. Cost and stability of peptide-based treatments may be challenges."},{"rthcId":"RPEP-15115","title":"Advances in Incretin-Based Therapies for MAFLD: Mechanisms and Clinical Evidence.","authors":"Dong, Wenqi; Zhang, Haiming; Mu, Shaowei; Shi, Shuyi; Zhang, Junli; Xu, Keshu","year":2026,"journal":"Clinical pharmacology and therapeutics, 119(2), 336-349","doi":"10.1002/cpt.70131","pmid":"41243582","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1RAs improve MAFLD/MASH through glucose and lipid metabolism regulation, with dual (GLP-1/GIP, GLP-1/GCR) and triple incretin agonists showing additional benefits in phase II trials for weight, insulin resistance, and liver parameters.","whyItMatters":"MAFLD affects about 30% of the global population and can progress to cirrhosis and liver cancer. Incretin-based peptide drugs offer the first promising pharmaceutical treatment approach.","specificNumbers":"","methodology":"Narrative review of mechanisms and clinical evidence for incretin-based therapies in MAFLD/MASH, covering GLP-1RAs, dual agonists, and triple agonists.","limitations":"Most data from phase II trials with relatively short follow-up. Whether liver histology improvements prevent cirrhosis long-term is unknown. Patient selection criteria vary across trials."},{"rthcId":"RPEP-15116","title":"From venom peptides to neurotherapeutics: BmK defensins and short-chain peptides as modulators of ion channels.","authors":"Dong, Yin; Wang, Jiajun; Zhu, Yudan; Zhao, Lu; Zeng, Yunqing; Tang, Lele; Xiao, Qian; Cheng, Jiwei; Wang, Chao; Tao, Jie","year":2026,"journal":"Frontiers in pharmacology, 17, 1754290","doi":"10.3389/fphar.2026.1754290","pmid":"41693793","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BmK defensins and short-chain toxins selectively modulate Kv1.3, BK, TRPV1, and chloride channels with pharmacological advantages including efficient tissue penetration, target specificity, low immunogenicity, and engineering versatility for neurological drug development.","whyItMatters":"Neurological conditions like epilepsy and chronic pain have limited treatments. Scorpion venom peptides offer highly specific ion channel modulators that could become the next generation of neurological drugs.","specificNumbers":"","methodology":"Comprehensive review of structural, functional, and pharmacological studies on BmK venom peptides targeting neuronal ion channels, with focus on drug development potential.","limitations":"Most candidates are at preclinical stage. Blood-brain barrier penetration needs in vivo confirmation for each candidate. Manufacturing costs for peptide therapeutics remain high."},{"rthcId":"RPEP-15117","title":"Incretin Dominance and Emerging Mechanisms in Obesity Pharmacotherapy: Insights from 275 Registered Clinical Trials (2019-2024).","authors":"Dos Santos Barbosa, Lucas Antônio; Almarie, Bassel; Moreira, Eduardo Luiz Gasnhar","year":2026,"journal":"Therapeutic innovation & regulatory science, 60(1), 223-247","doi":"10.1007/s43441-025-00875-y","pmid":"40993341","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Incretin pathway modulators comprised 69.8% of 275 obesity drug trials (2019-2024), with 40.7% in Phase 2 and 31.3% in Phase 3. Early-stage innovation was limited at 3.3%, and drug repurposing accounted for 22.2%.","whyItMatters":"While incretin drugs are effective, relying on a single mechanism class for obesity treatment creates risks—if long-term safety issues emerge, few alternatives will be ready.","specificNumbers":"","methodology":"Systematic review of clinical trials registered on ClinicalTrials.gov from October 2019 to October 2024, analyzing pharmacological interventions for obesity across development stages.","limitations":"Only covers ClinicalTrials.gov registrations; may miss some international trials. Pipeline snapshot from a specific time window. Cannot predict which candidates will succeed."},{"rthcId":"RPEP-15118","title":"Association between glucagon-like peptide-1 receptor agonists and colorectal cancer survival: A population-based cohort study.","authors":"Dosda, Arnaud; Fauchier, Grégoire; Sabbah, Nadia; Fauchier, Laurent; Lecomte, Thierry; Ducluzeau, Pierre Henri","year":2026,"journal":"Diabetes & metabolism, 52(2), 101734","doi":"10.1016/j.diabet.2026.101734","pmid":"41547436","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1RA users had significantly reduced all-cause mortality (HR 0.58, 95% CI 0.45-0.76, p<0.001) and metastasis-free survival (HR 0.60, 95% CI 0.40-0.87, p=0.01) compared to matched non-users.","whyItMatters":"Cancer patients with diabetes often face treatment decisions about continuing metabolic medications. This evidence supports that GLP-1 drugs may actually improve cancer outcomes.","specificNumbers":"","methodology":"Retrospective propensity-score-matched cohort study using TriNetX global health records (2010-2025) with 751 patients per cohort, analyzing overall and metastasis-free survival.","limitations":"Retrospective observational design. Cannot prove causation. Median follow-up ~2 years. GLP-1 users may have better overall health engagement."},{"rthcId":"RPEP-15119","title":"Functional characterization of Cr-CATHs: Novel antimicrobial peptides from the coastal bird Chroicocephalus ridibundus.","authors":"Dou, Haoran; Li, Shuangyu; Zhang, Pingchuan; Ye, Zifan; Li, Lili; Wang, Yipeng; Jiao, Xudong","year":2026,"journal":"Biochimie, 242, 59-76","doi":"10.1016/j.biochi.2025.12.008","pmid":"41421641","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Cr-CATH-1 demonstrated potent broad-spectrum antimicrobial activity with a triple mechanism of action (membrane disruption, DNA binding, ROS induction), low toxicity, and significant in vivo efficacy in a murine peritonitis model.","whyItMatters":"Drug-resistant infections kill over 1 million people annually. Novel AMPs from underexplored animal sources like birds could provide urgently needed new antibiotics with multiple killing mechanisms that resist resistance development.","specificNumbers":"","methodology":"Peptide identification and characterization including MIC assays, bactericidal kinetics, biofilm and persister cell assays, cytotoxicity/hemolysis testing, membrane disruption studies, DNA binding assays, ROS detection, and in vivo murine peritonitis model.","limitations":"Only tested in a mouse peritonitis model. Pharmacokinetics, optimal dosing, and manufacturing feasibility not addressed. Aquaculture applications mentioned but not validated."},{"rthcId":"RPEP-15120","title":"Ectopic, hepatic GLP-1R agonism enhances the weight loss efficacy of GLP-1 analogues.","authors":"Douros, Jonathan D; Capozzi, Megan; Novikoff, Aaron; Mokrosinski, Jacek; DuBois, Barent; Stock, Joseph; Rohlfs, Rebecca; Anderson, Mikayla; Jedrzejcyk, Dominika J; Poulsen, Svend; Blenke, Erik Oude; Dago, Tomas; Huus, Kasper; Nørby, Peder L; Kobberup, Sune; Rivir, Marita; Sorrell, Joyce; Mowery, Stephanie A; Drucker, Daniel J; D'Alessio, David A; Campbell, Jonathan E; Müller, Timo D; Perez-Tilve, Diego; Finan, Brian; Knerr, Patrick J","year":2026,"journal":"Molecular metabolism, 105, 102327","doi":"10.1016/j.molmet.2026.102327","pmid":"41654015","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"AAV-mediated ectopic GLP-1R expression in hepatocytes combined with semaglutide or dual GLP-1R/GIPR agonist treatment enhanced energy expenditure and weight loss compared to peptide treatment alone in diet-induced obese mice.","whyItMatters":"This proof-of-concept shows a novel approach to achieving the energy expenditure benefits of triple agonists without the cardiovascular risks of glucagon receptor activation.","specificNumbers":"","methodology":"Adeno-associated virus (AAV) delivery of liver-specific GLP-1R in wild-type diet-induced obese mice, followed by treatment with semaglutide, NNC5840 (cAMP-biased GLP-1R analogue), or dual GLP-1R/GIPR agonist, with energy expenditure and weight monitoring.","limitations":"Mouse model only. AAV-mediated gene therapy adds complexity and cost. Long-term effects of ectopic hepatic GLP-1R expression unknown. Not immediately translatable to clinical use."},{"rthcId":"RPEP-15121","title":"The expanding landscape of GLP-1 medicines.","authors":"Drucker, Daniel J","year":2026,"journal":"Nature medicine, 32(1), 47-57","doi":"10.1038/s41591-025-04124-5","pmid":"41482564","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 medicines are expanding from diabetes/obesity to cardiovascular, neurological, hepatic, and autoimmune conditions, with next-generation multi-epitope peptides offering enhanced efficacy through combined hormonal pathway targeting.","whyItMatters":"GLP-1 drugs may become the most widely prescribed medication class in history. Understanding their expanding indications and evolving drug design is essential for clinicians across specialties.","specificNumbers":"","methodology":"Narrative review of safety, efficacy, and emerging indications for current and pipeline GLP-1 medicines.","limitations":"Many emerging indications are still investigational. Long-term safety of chronic use across diverse populations needs monitoring. Access and cost remain barriers globally."},{"rthcId":"RPEP-15122","title":"EXPRESS: CGRP Expression and Signaling Sensitization in a Mouse Model of Chronic Oxaliplatin-Induced Peripheral Neuropathy.","authors":"Du, Junwei; Sudlow, Leland C; Satish, Kanishk; Villagomez, Abraham; Hu, Hongzhen; Berezin, Mikhail Y; Johnson, Maggie","year":2026,"journal":"Molecular pain, 17448069261432028","doi":"10.1177/17448069261432028","pmid":"41757721","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Chronic oxaliplatin treatment did not increase CGRP expression or neuron proportion but caused 2-fold Ramp1 upregulation, suggesting CGRP signaling enhancement through receptor sensitization and increased calcium-dependent release rather than peptide upregulation.","whyItMatters":"Understanding that CGRP signaling can be enhanced without increased peptide levels has implications for anti-CGRP therapy—receptor sensitization may be more important than peptide quantity in some pain conditions.","specificNumbers":"","methodology":"Eight-week chronic oxaliplatin treatment in mice with behavioral testing (cold allodynia), nerve conduction studies, qPCR and protein analysis of DRG, immunofluorescence for CGRP neurons, and RNA-seq for pathway analysis.","limitations":"Mouse model may not fully recapitulate human CIPN. Sex-specific differences (CGRP decrease in females) complicate interpretation. Increased release hypothesis needs direct experimental confirmation."},{"rthcId":"RPEP-15123","title":"Skin-penetrating peptides derived from computational simulation improve transdermal absorption and facilitate topical treatment of melanoma.","authors":"Du, Sanjiang; Wang, Hanlin; Geng, Feiyang; Zhang, Zongxu; Liu, Chenghao; Lu, Weiyue; Wei, Gang","year":2026,"journal":"Acta pharmaceutica Sinica. B, 16(2), 1140-1154","doi":"10.1016/j.apsb.2025.12.026","pmid":"41685147","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Computationally redesigned penetratin derivative (589WP) significantly improved transdermal delivery and, when conjugated to floxuridine in a topical gel, outperformed higher doses of free drug in melanoma inhibition without skin toxicity.","whyItMatters":"Topical cancer treatment could avoid the systemic side effects of intravenous chemotherapy. This computationally designed peptide delivery system demonstrates the feasibility of skin-penetrating peptide-drug conjugates.","specificNumbers":"","methodology":"CPP screening, computational simulation to identify permeability determinants, peptide redesign, in vitro skin permeability studies, in vivo fluorescence imaging, peptide-drug conjugation via ester linkage, and topical melanoma treatment model.","limitations":"Melanoma mouse model only. Ester linkage may limit conjugate stability. Manufacturing scalability of peptide-drug conjugates needs assessment. Skin penetration depth may be insufficient for deep tumors."},{"rthcId":"RPEP-15124","title":"A Human β-Defensin-Based Recombinant Protein DF2-HSA Ameliorates Cytokine Storm.","authors":"Du, Yibo; Yu, Zhuojun; Sheng, Weijin; Li, Yi; Hou, Lei; Zheng, Yanbo; Liu, Xiujun; Zhen, Yongsu","year":2026,"journal":"Cells, 15(2)","doi":"10.3390/cells15020202","pmid":"41597276","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"DF2-HSA reduced mortality in a cytokine storm mouse model while prolonging HBD-2 retention, decreasing multiple inflammatory cytokines, reducing vascular leakage, and alleviating lung and intestinal tissue damage.","whyItMatters":"Cytokine storms remain a major cause of death in sepsis and severe viral infections. An engineered defensin that both fights infection and controls inflammation could address both aspects simultaneously.","specificNumbers":"","methodology":"LPS-induced cytokine storm model in BALB/c athymic mice, with Luminex cytokine profiling, Evans blue vascular permeability assay, transmission electron microscopy, and histopathological analysis.","limitations":"Mouse model using athymic mice. LPS-induced cytokine storm may not fully replicate human sepsis or viral-induced storms. Dosing optimization and safety profiling needed."},{"rthcId":"RPEP-15125","title":"IL-27, a metabolic regulator secreted by astrocytes in response to GLP-1RA OHP2, modulates microglial reprogramming in Alzheimer's disease by regulating cGAS lactylation.","authors":"Du, Yixuan; Wu, Lingxi; Mao, Yang; Chen, Song; Gao, Xiangdong","year":2026,"journal":"Journal of neuroinflammation, 23(1), 58","doi":"10.1186/s12974-025-03683-1","pmid":"41527082","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"OHP2 induced IL-27 secretion from astrocytes, which modulated microglial reprogramming from neurotoxic M1 to neuroprotective M2 phenotype via glycolysis/cGAS lactylation clock/mTOR pathway, alleviating neuroinflammation.","whyItMatters":"An oral GLP-1 drug that crosses the blood-brain barrier and reduces Alzheimer's inflammation through a newly identified mechanism could provide accessible, disease-modifying treatment.","specificNumbers":"","methodology":"In vivo treatment of AD mouse models with oral OHP2, analysis of astrocyte IL-27 secretion, microglial phenotype profiling, and mechanistic pathway dissection.","limitations":"Mouse model of AD. The M1/M2 microglial classification is oversimplified. OHP2 is not yet in human trials. The glycolysis/cGAS lactylation pathway needs validation in human tissue."},{"rthcId":"RPEP-15126","title":"pH-responsive polydopamine-shelled 3D-printed chitosan/collagen hydrogel integrating exosomes and an enzyme/peptide cascade for diabetic wound healing.","authors":"Du, Yunxia; Xiao, Di; Ren, Changle; Li, Zhenlan; Wang, Xiaofeng; Zhao, Yantao; Jiang, Yongmei","year":2026,"journal":"Biomaterials science, 14(5), 1332-1355","doi":"10.1039/d5bm01823d","pmid":"41685930","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The pH-responsive 3D-printed scaffold achieved tiered release of AMPs/GOx/SOD (early antibacterial/antioxidant) followed by Exo/EGF (later regeneration), significantly accelerating wound closure across three animal models.","whyItMatters":"Diabetic wounds affect millions and lead to amputations. A smart wound dressing that fights infection, reduces oxidative stress, and then promotes healing in sequence could dramatically improve outcomes.","specificNumbers":"","methodology":"3D-printed CS/Col hydrogel with PDA pH-responsive coating, characterized for printability, mechanical properties, and bioactivity. Tested in vitro (macrophage polarization, cell migration) and in vivo (diabetic rat, infectious dermatitis mouse, rabbit ear wound models).","limitations":"Animal models only. Manufacturing scalability of 3D-printed hydrogels uncertain. Cost and regulatory pathway for multi-component wound dressings complex. Long-term outcomes not assessed."},{"rthcId":"RPEP-15127","title":"Antimicrobial peptides and proteins: Mechanism of action and therapeutic potential.","authors":"Dubey, Ateendra Kumar; Mishra, Amit; Prajapati, Vijay Kumar","year":2026,"journal":"Advances in protein chemistry and structural biology, 149, 143-170","doi":"10.1016/bs.apcsb.2025.07.001","pmid":"41581931","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Several AMPs are already clinically approved with defined pharmacology, and emerging peptide modifications, delivery technologies, and AI-based discovery tools are expanding the therapeutic pipeline.","whyItMatters":"AMPs are no longer just laboratory curiosities—they are approved drugs treating drug-resistant infections. Understanding the full clinical landscape helps researchers develop better ones faster.","specificNumbers":"","methodology":"Comprehensive narrative review covering AMP fundamentals, clinical pharmacology of approved AMPs, modification strategies, delivery systems, and computational discovery tools.","limitations":"Broad scope limits depth on individual drugs. Rapidly evolving AI tools may quickly outdate computational sections. Not a systematic review."},{"rthcId":"RPEP-15128","title":"Weight reduction and treatment adherence with tirzepatide using the Individualized Virtual Integrative Medicine (IVIM) protocol.","authors":"Duncan, Jessica; Stevens, Patrick Lee; Bigby, Emily; Floyd, Courtney; Malina, Josh; Nickens, Jennifer; Lambert, Amber; Kantor, Taylor","year":2026,"journal":"Obesity pillars, 17, 100236","doi":"10.1016/j.obpill.2025.100236","pmid":"41438798","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"At 52 weeks, mean weight loss was 52.28 lbs (22.74%), with 99.36% achieving ≥5% TBWL, 97.12% ≥10%, 84.66% ≥15%, 64.22% ≥20%, and 41.21% ≥25%. At 72 weeks, mean loss was 62.79 lbs (26.54%).","whyItMatters":"These real-world results exceed most clinical trial outcomes for tirzepatide, suggesting that individualized virtual support and dose titration can maximize GLP-1 drug effectiveness.","specificNumbers":"","methodology":"Retrospective analysis of 1,166 patients (BMI ≥30) completing ≥52 weeks on tirzepatide with IVIM telehealth protocol, including board-certified obesity medicine oversight.","limitations":"Retrospective design. No control group. Includes both branded and compounded tirzepatide. Patients who completed 52 weeks are self-selected (completers analysis). IVIM program may attract more motivated patients."},{"rthcId":"RPEP-15129","title":"Development of Nanoparticle-Hydrogel Drug Delivery System for Sustained Release of Anti-VEGF Peptide in Ocular Neovascularization Treatment.","authors":"Durak, Saliha; Yetisgin, Abuzer Alp; Aciksari, Aysegul; Ceylan, Ramazan; Onder Tokuc, Ecem; Kutlu, Ozlem; Karabas, Veysel Levent; Cetinel, Sibel","year":2026,"journal":"Macromolecular bioscience, 26(1), e00263","doi":"10.1002/mabi.202500263","pmid":"41531389","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"HA-PGS NP@HRH achieved 42.54% drug release over 3 months, 55.19% inhibition of HUVEC viability, and suppression of neovascularization in an oxygen-induced retinopathy mouse model.","whyItMatters":"Reducing eye injection frequency from monthly to quarterly or longer would dramatically improve quality of life for millions of patients with wet AMD and diabetic eye disease.","specificNumbers":"","methodology":"PGS nanoparticle synthesis, hyaluronic acid hydrogel formulation, drug release kinetics, ARPE-19 and HUVEC cell viability/tube formation assays, and in vivo oxygen-induced retinopathy model in mice.","limitations":"Mouse OIR model doesn't perfectly replicate human wet AMD. Long-term intraocular safety needs assessment. Three-month release may still require periodic injections."},{"rthcId":"RPEP-15130","title":"Impact of glucagon-like peptide-1 receptor agonism-based therapies on limb outcomes in peripheral artery disease and type 2 diabetes: An updated systematic review and meta-analysis.","authors":"Dutta, Deep; Mahajan, Kunal; Kamrul-Hasan, Abul Bashar Mohammad; Mahajan, Nitin; Sharma, Meha; Vohra, Shekhar","year":2026,"journal":"Diabetes, obesity & metabolism, 28(3), 2075-2084","doi":"10.1111/dom.70391","pmid":"41424191","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In PAD patients: MALE OR 0.66 (p=0.05), revascularization OR 0.85 (p<0.001), mortality OR 0.55 (p=0.0008), MACE OR 0.68 (p=0.004). In T2D patients: MALE OR 0.70 (p=0.0005), amputations OR 0.58 (p<0.001).","whyItMatters":"PAD-related amputations devastate quality of life. A 42% reduction in amputations from GLP-1 drugs could save thousands of limbs annually.","specificNumbers":"","methodology":"Systematic review and meta-analysis of 10 PAD studies (352,743 patients) and 7 T2D studies (1,759,799 patients) evaluating GLP-1 RA-based therapies on limb and cardiovascular outcomes.","limitations":"High heterogeneity in mortality analysis (I² up to 97%). Mix of observational and trial data. Cannot determine optimal GLP-1 drug or dose for PAD."},{"rthcId":"RPEP-15131","title":"Antibacterial peptidomimetics via fragment display on small-molecule scaffolds.","authors":"Dyhr, Emma; Cañete de Pinedo, Lucía; Frederiksen, Nicki; Bojer, Martin Saxtorph; Ingmer, Hanne; Sæbø, Ingvill Pedersen; Ræder, Synnøve Brandt; Bjørås, Magnar; Helgesen, Emily; Booth, James Alexander; Franzyk, Henrik","year":2026,"journal":"RSC medicinal chemistry","doi":"10.1039/d5md00916b","pmid":"41782641","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Several scaffold-based peptidomimetics achieved MICs ≤8 μg/mL (~3 μM) against pathogenic bacteria, with full activity retained against drug-resistant E. coli and a bactericidal mechanism confirmed at 2× MIC.","whyItMatters":"These scaffold-based peptidomimetics bridge the gap between natural AMPs (effective but unstable) and small-molecule drugs (stable but increasingly resisted), offering a new compound class for the antibiotic resistance crisis.","specificNumbers":"","methodology":"Synthesis of peptidomimetics using bis-, tris-, and tetrakis(bromomethyl)benzene and triamine scaffolds; MIC testing against Gram-positive and Gram-negative panel; drug-resistant E. coli testing; hemolysis and cell viability assays.","limitations":"In vitro activity only. In vivo efficacy, pharmacokinetics, and toxicity not assessed. Limited to a few scaffold types. Safety window needs optimization for some compounds."},{"rthcId":"RPEP-15132","title":"From speciation to action: Cu(II) and Zn(II) tune histatins, but pH and enamel drive efficacy.","authors":"Dzień, Emilia; Mikołajczyk-Tarnawa, Aleksandra; Matera-Witkiewicz, Agnieszka; Szewczyk, Krzysztof; Barceló-Oliver, Miquel; Pawlik-Sobecka, Lilla; Wątły, Joanna; Rowińska-Żyrek, Magdalena","year":2026,"journal":"Dalton transactions (Cambridge, England : 2003), 55(1), 125-134","doi":"10.1039/d5dt02485d","pmid":"41327541","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Cu(II) and Zn(II) binding to histatins primarily reshapes peptide topology rather than activating antimicrobial mechanisms. Environmental pH and hydroxyapatite anchoring are proposed as the main drivers of in situ efficacy.","whyItMatters":"Reframes how we think about histatin-based therapeutics: focus on positioning peptides correctly (pH, surface) rather than optimizing metal binding for better oral antimicrobial products.","specificNumbers":"","methodology":"Metal binding quantification (Cu(II), Zn(II)) by thermodynamics and spectroscopy for histatin 1 and fragments, antimicrobial activity testing against ATCC pathogens, and structure-activity correlation analysis.","limitations":"In vitro testing with ATCC strains may not reflect oral biofilm complexity. The proposed hydroxyapatite anchoring model needs direct experimental validation."},{"rthcId":"RPEP-15133","title":"Thymic stromal lymphopoietin (TSLP) - pro-inflammatory cytokine and antimicrobial peptide.","authors":"Döhner, Katinka; John, Ojonugwa Precious; Werfel, Thomas","year":2026,"journal":"Biochimica et biophysica acta. Molecular cell research, 120127","doi":"10.1016/j.bbamcr.2026.120127","pmid":"41791676","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Human TSLP exists as two functionally distinct isoforms: long-form TSLP acts as a pro-inflammatory cytokine in atopic and neoplastic diseases, while short-form TSLP functions as an anti-inflammatory antimicrobial peptide at barrier surfaces.","whyItMatters":"Understanding that one gene produces both a disease-driving cytokine and a protective antimicrobial peptide has important implications for therapeutic targeting—ideally blocking the harmful form while preserving the beneficial one.","specificNumbers":"","methodology":"Narrative review of TSLP biology, focusing on isoform differences, disease associations, SNP effects, and therapeutic targeting with tezepelumab.","limitations":"The relative contributions of lfTSLP vs sfTSLP in most diseases are not fully characterized. Whether tezepelumab differentially blocks the two forms is not clear. Most genetic association data are from European populations."},{"rthcId":"RPEP-15134","title":"Oral (poly)peptide delivery: On the emulsifying properties of inverted lipid phases under gastrointestinal conditions.","authors":"Ebert, Melanie Lena; Postina, Annika; Schmidt, Marlene Ramona; Laffleur, Flavia; Kali, Gergely; Bernkop-Schnürch, Andreas","year":2026,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 390, 114508","doi":"10.1016/j.jconrel.2025.114508","pmid":"41352642","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Self-emulsifying ILP (se-ILPdry) achieved 12.10% oral bioavailability for HRP polypeptide vs 1.54% for non-emulsifying ILPdry, with rapid and complete emulsification in gastric and intestinal fluids.","whyItMatters":"Achieving 12% oral bioavailability for a polypeptide is remarkable and could enable oral formulations of injectable peptide drugs, improving patient compliance.","specificNumbers":"","methodology":"Formulation development of ILP and se-ILP (dry and wet), emulsification characterization via turbidity in bile salt media, kinetics in simulated GI fluids, and in vivo oral pharmacokinetics in rats using HRP as model polypeptide.","limitations":"Tested with HRP as model polypeptide, which may not predict results for therapeutic peptides. Rat GI conditions differ from human. Long-term stability of formulations not assessed."},{"rthcId":"RPEP-15135","title":"Liraglutide in mild to moderate Alzheimer's disease: a phase 2b clinical trial.","authors":"Edison, Paul; Femminella, Grazia Daniela; Ritchie, Craig; Nowell, Joseph; Holmes, Clive; Walker, Zuzana; Ridha, Basil; Raza, Sanara; Livingston, Nicholas R; Frangou, Eleni; Love, Sharon; Williams, Gareth; Lawrence, Robert; Mcfarlane, Brady; Archer, Hilary; Coulthard, Elizabeth; Underwood, Benjamin R; Koranteng, Paul; Karim, Salman; Bannister, Carol; Perneczky, Robert; Prasanna, Aparna; Junaid, Kehinde; McGuinness, Bernadette; Nilforooshan, Ramin; Macharouthu, Ajay; Donaldson, Andrew; Thacker, Simon; Russell, Gregor; Malik, Naghma; Mate, Vandana; Knight, Lucy; Kshemendran, Sajeev; Holscher, Christian; Mansouri, Anita; Chester-Jones, Mae; Holmes, Jane; Tan, Trisha; Williams, Steve; Ashraf, Azhaar; Brooks, David J; Harrison, John; Hinz, Rainer; Tadros, George; Passmore, Anthony Peter; Ballard, Clive","year":2026,"journal":"Nature medicine, 32(1), 353-361","doi":"10.1038/s41591-025-04106-7","pmid":"41326666","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Primary outcome (cerebral glucose metabolic rate) showed no significant change (difference -0.17, p=0.14). Secondary outcome ADAS-Exec favored liraglutide (0.15, p=0.01). Safety was confirmed in non-diabetic AD patients.","whyItMatters":"This is the largest and most rigorous GLP-1 drug trial for Alzheimer's to date. While the primary endpoint was missed, the cognitive benefit signal supports continued investigation of GLP-1 drugs for AD.","specificNumbers":"","methodology":"Multicenter, randomized, double-blind, placebo-controlled phase 2b trial (ELAD, NCT01843075) with 204 participants receiving daily liraglutide or placebo for 52 weeks, with FDG-PET, MRI, and neuropsychometric assessments.","limitations":"Missed primary endpoint. Secondary cognitive benefit was on a single measure. 52 weeks may be too short to detect meaningful changes in brain metabolism. 204 patients may be underpowered for some endpoints."},{"rthcId":"RPEP-15136","title":"Tirzepatide reduces alcohol drinking and relapse-like behaviours in rodents.","authors":"Edvardsson, Christian E; Adermark, Louise; Gottlieb, Sam; Alfreji, Safana; Emous, Thaynnam A; Gouda, Yomna; Thorsell, Annika; Vujičić, Milica; Aranäs, Cajsa; Benrick, Anna; Wernstedt Asterholm, Ingrid; Lopez, Marcelo F; Becker, Howard C; Jerlhag, Elisabet","year":2026,"journal":"EBioMedicine, 124, 106119","doi":"10.1016/j.ebiom.2025.106119","pmid":"41506148","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tirzepatide attenuated alcohol reward (dopamine release p<0.001), dose-dependently reduced intake (p<0.001), prevented binge (p<0.01) and relapse drinking (p<0.001), with sustained efficacy, and induced lasting synaptic depression and histone changes in the lateral septum.","whyItMatters":"This is the most comprehensive preclinical study of a GLP-1/GIP agonist for alcohol use disorder, providing both behavioral and mechanistic evidence that could support human clinical trials.","specificNumbers":"","methodology":"Comprehensive rodent behavioral battery (locomotor activity, CPP, two-bottle choice, drinking in the dark, alcohol deprivation effect), microdialysis, electrophysiology, and proteomics in the lateral septum.","limitations":"Rodent models; alcohol consumption patterns differ from human AUD. Lateral septum mechanisms need human validation. Cannot determine relative contributions of GLP-1R vs GIPR agonism."},{"rthcId":"RPEP-15137","title":"Tirzepatide in dermatology: cutaneous adverse events, emerging therapeutic roles, and cosmetic implications - A comprehensive review.","authors":"El-Amawy, Heba Saed","year":2026,"journal":"Anais brasileiros de dermatologia, 101(1), 501255","doi":"10.1016/j.abd.2025.501255","pmid":"41483501","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tirzepatide causes injection-site reactions comparable to semaglutide, rare severe dermatologic events, and facial volume loss from rapid weight loss, but shows immunomodulatory potential for inflammatory skin diseases.","whyItMatters":"As millions take tirzepatide, understanding its skin effects—both adverse and potentially therapeutic—helps dermatologists, prescribers, and patients make informed decisions.","specificNumbers":"","methodology":"Narrative review of SURPASS clinical trials, case reports, pharmacovigilance data (PubMed, Scopus, Google Scholar through May 2025) focusing on dermatologic effects.","limitations":"Therapeutic skin benefits based on case reports only. Cosmetic effects are subjective. Pharmacovigilance data may underrepresent events."},{"rthcId":"RPEP-15138","title":"PIONEER REAL Saudi Arabia: A multicentre, prospective, real-world study of once-daily oral semaglutide use in adults with type 2 diabetes in Saudi Arabia.","authors":"ElBadawi, Hussein; Albalkhi, Nader; Al Kadhim, Ibrahim; Elsadig, Ahmed; Baltzis, Dimitrios; Hatahet, Mohamed Hassan; Ismail, Mahmoud; Khader, Said; Rasmussen, Christina Louise; Scheuer, Stine Hedegaard; Shalaby, Ahmed; Almehthel, Mohammed","year":2026,"journal":"Diabetes, obesity & metabolism, 28(2), 1304-1314","doi":"10.1111/dom.70317","pmid":"41309294","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Oral semaglutide reduced HbA1c by -1.0% (p<0.0001), body weight by -4.4 kg (p<0.0001), and waist circumference by -4.3 cm (p<0.0001), with 61.9% achieving HbA1c <7% and significant treatment satisfaction improvement.","whyItMatters":"Real-world data from Middle Eastern populations complement clinical trials and confirm oral semaglutide's effectiveness across diverse ethnic and dietary contexts.","specificNumbers":"","methodology":"34-44 week multicenter prospective open-label real-world study in 192 Saudi adults with T2D initiating oral semaglutide, using DTSQs/DTSQc satisfaction measures.","limitations":"Open-label, no control group. Only 139 of 192 completed the study. Half switched away from oral semaglutide by end of study."},{"rthcId":"RPEP-15139","title":"Renin-angiotensin system activation and oxidative stress in hospitalized COVID-19 patients: a single-centre prospective observational study.","authors":"Eleuteri, Davide; Del Tedesco, Filippo; Silvia, Federico; Tucciariello, Caterina; Ruggiero, Ersilia; Gervasoni, Jacopo; Santucci, Lavinia; Primiano, Aniello; Petrucci, Martina; Torelli, Ernico; Cianci, Rossella; Giannarelli, Diana; Cutuli, Salvatore Lucio; De Pascale, Gennaro; Bello, Giuseppe; Maria, Calabrese; Masullo, Matteo; Urbani, Andrea; Di Santo, Riccardo; Antonelli, Massimo; Montini, Luca","year":2026,"journal":"Intensive care medicine experimental, 14(1), 15","doi":"10.1186/s40635-026-00857-w","pmid":"41663785","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Worsening COVID-19 patients showed rising renin and Ang I (p<0.001), declining Ang II/Ang I ratio (p<0.001), increasing Ang 1-7 (p<0.001), and rising ADMA (p<0.001), with 28-day outcomes predicted by renin, Ang I, Ang 1-7, and ADMA.","whyItMatters":"Understanding how RAS peptides change during COVID-19 could improve risk stratification and guide the use of RAS-targeting therapies in critically ill patients.","specificNumbers":"","methodology":"Single-center prospective observational study of 155 hospitalized COVID-19 patients with plasma RAS peptides and ADMA measured at admission (D0) and day 3 (D3), stratified by WHO respiratory trajectory.","limitations":"Single-center. Observational design. Only two timepoints measured. Cannot determine if RAS changes drive disease or result from it."},{"rthcId":"RPEP-15140","title":"The enhanced Wnt/β-catenin pathway upregulation by sacubitril/valsartan via neprilysin inhibition compared to valsartan in the rotenone induced Parkinson's disease rat model.","authors":"Elkhial, Rania Tarek; Awny, Magdy M; El-Sayed, Elsayed K; Nofal, Shahira","year":2026,"journal":"Neuropharmacology, 283, 110734","doi":"10.1016/j.neuropharm.2025.110734","pmid":"41138763","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"SAC/VAL was more neuroprotective than VAL alone in PD rats, likely through neprilysin inhibition boosting natriuretic peptides that activate the WNT/β-catenin pathway, while reducing oxidative stress and neuroinflammation.","whyItMatters":"Drug repurposing an approved heart failure medication for Parkinson's would be much faster and cheaper than developing new drugs. The natriuretic peptide mechanism provides a novel neuroprotective pathway.","specificNumbers":"","methodology":"Rotenone-induced PD model in male Wistar rats, with oral SAC/VAL (40 mg/kg/day) or VAL (20 mg/kg/day) for 6 weeks, assessing behavior, dopaminergic injury, DA/TH/NP levels, WNT/β-catenin pathway, and oxidative/inflammatory markers.","limitations":"Rat model; rotenone-induced PD doesn't fully replicate human PD. Cannot separate all effects of SAC from VAL. Dosing may not translate directly to humans. Short treatment duration."},{"rthcId":"RPEP-15141","title":"Evaluating the Effects of Glucagon-Like Peptide 1 Receptor Agonists as a Secondary Prevention in Peripheral Arterial Disease: A Meta-Analysis.","authors":"Elliott, Beth; Tomlinson, Ellie; Desai, Nirali; Heald, Adrian; Field, Benjamin C; Heiss, Christian; Whyte, Martin B","year":2026,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders","doi":"10.1007/s13300-026-01843-x","pmid":"41697522","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 5 RCTs (25,067 patients), GLP-1 RAs showed non-significant trends for revascularization (OR 0.87, 95% CI 0.73-1.05, p=0.13) and amputations (OR 0.82, 95% CI 0.53-1.27, p=0.37) in PAD patients.","whyItMatters":"Separating RCT evidence from observational data provides a more accurate picture of GLP-1 drugs' true effects on PAD limb outcomes, tempering earlier enthusiasm while not ruling out benefit.","specificNumbers":"","methodology":"Systematic review and meta-analysis of randomized controlled trials only (5 studies, 25,067 patients), using Cochrane methodology and random-effects models.","limitations":"Only 5 RCTs met criteria. Limited amputation events (224). PAD was not the primary endpoint in most included trials. May be underpowered for limb-specific outcomes."},{"rthcId":"RPEP-15142","title":"Semaglutide-Induced Atypical Pustular Drug Eruption: A Case Report.","authors":"Elliott, Destinee C; Veon, Francesca L; McBride, Jeffrey D; Levin, Jarad","year":2026,"journal":"Cureus, 18(1), e101016","doi":"10.7759/cureus.101016","pmid":"41658769","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"An AGEP-like skin reaction after semaglutide dose increase was attributed to the excipient propylene glycol rather than semaglutide, highlighting the importance of ingredient analysis in adverse drug reactions.","whyItMatters":"With millions taking semaglutide, understanding that adverse reactions may be caused by excipients rather than the active peptide itself has important implications for patient management and formulation alternatives.","specificNumbers":"","methodology":"Single case report with clinical documentation, histopathological analysis, and systematic ingredient/excipient investigation.","limitations":"Single case report. Cannot definitively prove propylene glycol causation. The atypical AGEP timeline complicates diagnosis."},{"rthcId":"RPEP-15143","title":"GLP-1 is associated with perfectionism in Swedish women with anorexia nervosa, independent of BMI.","authors":"Elm, Sofia; Petersson, Suzanne; Carlsson, Martin; Brudin, Lars; Marteinsdottir, Ina; Wanby, Pär","year":2026,"journal":"Eating and weight disorders : EWD","doi":"10.1007/s40519-026-01831-x","pmid":"41775940","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Non-weight-restored AN patients had elevated fasting GLP-1 (29 vs 16 pg/mL, p=0.048) and GIP (37 vs 5 pmol/L, p=0.048). GLP-1 strongly correlated with perfectionism (r=0.768, p=0.001) independent of BMI.","whyItMatters":"If elevated GLP-1 perpetuates anorexia symptoms by maintaining early satiety, this opens a new understanding of AN biology and raises caution about GLP-1 drug use in eating disorder populations.","specificNumbers":"","methodology":"Cross-sectional pilot study of 17 women (10 AN, 7 controls) with fasting blood sampling for incretins and self-assessment psychiatric scales (EDI-3, EDE-Q, STAI, MADRS-S, OCI-R).","limitations":"Very small sample size (17 total). Pilot study. Cross-sectional design—cannot determine causality. GLP-1 levels may be affected by nutritional status."},{"rthcId":"RPEP-15144","title":"IUPHAR review: From foe to friend: Repurposing glucagon to treat obesity and type 2 diabetes.","authors":"Elmendorf, Andrew J; Yousefian, Mostafa; Kim, Il-Man; Hardaway, J Andrew; Habegger, Kirk; Flak, Jonathan N","year":2026,"journal":"Pharmacological research, 223, 108077","doi":"10.1016/j.phrs.2025.108077","pmid":"41478576","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Glucagon receptor agonism enhances weight loss through energy expenditure stimulation when combined with GLP-1R and/or GIPR agonism, with dual (survodutide, cotatutide, mazdutide) and triple (retatrutide) agonists in clinical development.","whyItMatters":"Current GLP-1 drugs cause weight loss mainly by reducing food intake. Adding glucagon receptor agonism could produce more durable weight loss by also burning more calories—addressing the main limitation of current therapy.","specificNumbers":"","methodology":"IUPHAR-commissioned narrative review of preclinical evidence for glucagon receptor agonism mechanisms and clinical data on emerging dual and triple agonist peptide therapeutics.","limitations":"Most GCGR agonism evidence is preclinical in rodents. Human clinical data on dual/triple agonists are limited. Safety concerns include cardiovascular effects and hepatotoxicity."},{"rthcId":"RPEP-15145","title":"Exploring the effects of GLP-1 receptor agonists in fibromyalgia: a propensity-matched real-world cohort using the TriNetX research platform.","authors":"Eshak, Nouran; Irani, Anushka; Sullivan, Megan","year":2026,"journal":"Rheumatology (Oxford, England), 65(2)","doi":"10.1093/rheumatology/keag033","pmid":"41578948","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1RA use was associated with reduced opioid prescriptions (OR 0.65), pain diagnostic codes (OR 0.79), and fatigue codes (OR 0.68), all p<0.001, over 5-year follow-up in 96,050 matched fibromyalgia patients.","whyItMatters":"Fibromyalgia affects 2-4% of the population with no good treatments. A 35% reduction in opioid use is clinically significant and could reduce opioid dependence risk in this vulnerable population.","specificNumbers":"","methodology":"Retrospective propensity-matched cohort study using TriNetX (48,025 patients per group), with 5-year outcomes including opioid use, pain/fatigue/disability diagnostic codes, BMI, and HbA1c.","limitations":"Retrospective observational design. Uses diagnostic codes as proxies for symptoms (not validated fibromyalgia outcome measures). BMI/HbA1c differences persisted despite matching."},{"rthcId":"RPEP-15146","title":"Targeting neuroinflammation in neurodegenerative disorders: the emerging potential of semaglutide.","authors":"Evola, Vito; Parmar, Mayur S","year":2026,"journal":"Inflammation research : official journal of the European Histamine Research Society ... [et al.], 75(1), 13","doi":"10.1007/s00011-025-02166-6","pmid":"41504939","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide reduced CSF p-tau, t-tau, neurogranin, and inflammation marker YKL-40 in humans, but Phase 3 AD trials did not meet the CDR-SB cognitive primary endpoint despite favorable biomarker modulation.","whyItMatters":"If semaglutide can modify neuroinflammation across multiple diseases, it could become the first broadly applicable neuroprotective drug—but the disconnect between biomarker improvement and clinical endpoints needs resolution.","specificNumbers":"","methodology":"Comprehensive narrative review of preclinical and emerging clinical evidence for semaglutide's neuroprotective effects across neurodegenerative diseases.","limitations":"Phase 3 AD trials failed primary endpoint. BBB penetration is limited. Most non-AD evidence is preclinical. Extrapolation across different diseases requires disease-specific validation."},{"rthcId":"RPEP-15147","title":"Association of GLP-1 Receptor Agonist and SGLT2 Inhibitor with Cardiovascular Outcomes after Transcatheter Aortic Valve Replacement.","authors":"Fahoury, Alan M; Kamel-Abusalha, Louie; Didier, Alexander J; Wunderly, Kevin; Sarrouj, Sami; Issa, Rochell; Afifi, Ahmed; Gupta, Rajesh","year":2026,"journal":"The American journal of cardiology","doi":"10.1016/j.amjcard.2026.02.043","pmid":"41765256","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Post-TAVR: GLP-1 RA decreased all-cause mortality; SGLT2i decreased arrhythmia; combined GLP-1 RA + SGLT2i decreased mortality, MI, acute HF, and arrhythmia compared to untreated matched controls.","whyItMatters":"TAVR patients face high cardiovascular risk with limited evidence-based medical therapy. Adding GLP-1 drugs could improve survival in this growing patient population.","specificNumbers":"","methodology":"Retrospective propensity-matched cohort study using TriNetX database, comparing post-TAVR patients on GLP-1 RA, SGLT2i, both, or neither, with Kaplan-Meier survival analysis.","limitations":"Retrospective observational design. TAVR patients on these drugs may have different baseline characteristics. Cannot determine optimal timing to start therapy. Specific hazard ratios not provided in abstract."},{"rthcId":"RPEP-15148","title":"Peptide coacervate-Prussian blue hybrid supraparticle-tailored scaffolds for revitalizing diabetic heart valve regeneration via multiplex oxidative stress regulation.","authors":"Fan, Yang; Xingzhuang, Du; Zhiyu, Zhao; Gaoyang, Guo; Yunbing, Wang","year":2026,"journal":"Biomaterials, 327, 123798","doi":"10.1016/j.biomaterials.2025.123798","pmid":"41145022","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The SS-31/REDV/PBNP-functionalized scaffold reduced EC apoptosis, promoted EC proliferation and migration under hyperglycemia, suppressed macrophage inflammatory cytokines, and accelerated endothelialization in diabetic rabbit vascular models.","whyItMatters":"Diabetic patients need heart valve replacements but heal poorly. A scaffold that addresses the diabetic healing environment could enable tissue-engineered heart valves for this large patient population.","specificNumbers":"","methodology":"Peptide coacervate-PBNP supraparticle functionalization of decellularized scaffolds, in vitro EC/macrophage studies under hyperglycemic conditions, and in vivo implantation in diabetic rabbit vascular models.","limitations":"Rabbit vascular model; cardiac valve-specific conditions may differ. Short-term in vivo outcomes; long-term durability unknown. Manufacturing complexity."},{"rthcId":"RPEP-15149","title":"Selective peptide-guided transcytosis enhances extracellular vesicle-mediated siRNA delivery across the blood-brain barrier.","authors":"Fang, Jingwen; Zhang, Lingzhu; Wang, Ye; Chen, Menghan; He, Yanqiu; Zhang, Chen-Yu; Zhang, Yujing; Jiang, Xiaohong; Li, Jing","year":2026,"journal":"The Journal of biological chemistry, 302(1), 110942","doi":"10.1016/j.jbc.2025.110942","pmid":"41241103","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"RVG and CPP.16 modifications redirect sEVs into transcytotic rather than endocytic pathways. RVG-sEVs use clathrin-mediated endocytosis for superior BBB penetration and more efficient siRNA delivery to neurons and astrocytes in vivo.","whyItMatters":"Understanding how peptide modifications actually achieve brain delivery (transcytosis, not enhanced uptake) enables rational design of brain-targeting therapeutics for neurological diseases.","specificNumbers":"","methodology":"In vitro BBB model comparing RVG- and CPP.16-modified sEVs for internalization, transcytosis, pathway analysis, and gene silencing, with in vivo brain distribution studies in mice.","limitations":"Mouse models; human BBB may respond differently. Only siRNA cargo tested. Long-term safety of repeated peptide-modified EV administration unknown."},{"rthcId":"RPEP-15150","title":"Parathyroid hormone-related protein is a therapeutic target in idiopathic pulmonary fibrosis.","authors":"Fang, Xue-Quan; Lim, Suha; Lee, Yoon-Mi; Lim, Chang-Hoon; Kim, Han-Byeol; Joo, Jeong Ho; Han, Sang-Woo; Kim, Seohyun; Kim, Ji Hyung; Na, Kwon Joong; Park, Samina; Kim, Young Tae; Park, Jimyung; Park, Jooho; Lee, Jeong Seok; Shin, Eun-Young; Kim, Eung-Gook; Shin, Hyun-Woo; Lim, Ji-Hong","year":2026,"journal":"Signal transduction and targeted therapy, 11(1)","doi":"10.1038/s41392-026-02578-8","pmid":"41724741","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"PTHrP1-34 was elevated in IPF lung tissue and bronchoalveolar lavage, activated fibroblasts and ECM production, and targeting the PTHrP1-34/PTH1R axis with antibodies, peptides, or gene silencing attenuated pulmonary fibrosis in mice.","whyItMatters":"IPF affects 3 million people worldwide with a median survival of 3-5 years. A new druggable peptide target could lead to the first disease-modifying therapy.","specificNumbers":"","methodology":"Bulk and single-cell RNA-seq reanalysis of human IPF tissue, immunohistochemistry in IPF patients and bleomycin-treated mice, cell-based fibroblast activation assays, and preclinical evaluation of three therapeutic strategies in bleomycin mouse model.","limitations":"Bleomycin mouse model doesn't fully replicate human IPF. Therapeutic strategies tested short-term. Human clinical translation needs validation."},{"rthcId":"RPEP-15151","title":"An Engineered Solidified Peptide Hemocyte Sponge as Nanomotor Storage to Combat Bacterial Colitis.","authors":"Fang, Yuxin; Yan, Jianming; Yu, Tongxin; An, Zichuan; Lv, Kaikai; Xue, Chenyu; Yu, Hongyang; Dong, Na; Shan, Anshan","year":2026,"journal":"Advanced science (Weinheim, Baden-Wurttemberg, Germany), 13(8), e15620","doi":"10.1002/advs.202515620","pmid":"41317396","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Immobilized peptide-based nanomotors coated with RBC membranes captured endotoxins structure-independently via electrostatic interactions, prevented pro-inflammatory cytokine release, and managed bacterial colitis through endotoxin sequestration.","whyItMatters":"Drug-resistant infections need alternatives beyond antibiotics and structure-specific antibodies. A universal endotoxin capture system could treat diverse bacterial infections regardless of the specific pathogen.","specificNumbers":"","methodology":"Design and fabrication of peptide-Ni2+-coordinated nanomotors with RBC membrane coating, endotoxin capture assays, pro-inflammatory cytokine analysis, and colitis treatment model.","limitations":"In vivo testing limited to colitis model. Manufacturing complexity of multi-component nanomotors. Long-term safety of Ni2+-coordinated systems unknown. Scale-up challenges."},{"rthcId":"RPEP-15152","title":"Gastrointestinal dysmotility and impaired gut peptide-satiety coupling in men with spinal cord injury.","authors":"Farkas, Gary J; Cunningham, Paige M; Berg, Arthur S; Jimsheleishvili, George; Mendez, Armando J; Gater, David R; Nash, Mark S; Rolls, Barbara J","year":2026,"journal":"Physiology & behavior, 305, 115207","doi":"10.1016/j.physbeh.2025.115207","pmid":"41407179","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"SCI patients showed GI dysmotility, exaggerated glycemic excursions, weakened ghrelin-hunger and GLP-1-fullness coupling (p<0.05), a shift toward glucose-driven satiety signals, and enhanced insulin-GLP-1 association.","whyItMatters":"Obesity after SCI significantly worsens health outcomes. Understanding that gut peptide signaling is disrupted opens new therapeutic targets—potentially including GLP-1 drugs.","specificNumbers":"","methodology":"Pilot study with 16 men with SCI and 16 controls consuming standardized meals (195g and 390g), measuring SmartPill GI motility, postprandial GI peptides, glucose, insulin, triglycerides, and hunger/satiety ratings.","limitations":"Small pilot study (n=32). Men only. Cross-sectional design. Cannot determine causation between disrupted signaling and obesity."},{"rthcId":"RPEP-15153","title":"Prospects of GLP-1 Therapies for Addiction and Mental Health Comorbidities-Quo Vadis?: A Review.","authors":"Farokhnia, Mehdi; Leggio, Lorenzo","year":2026,"journal":"JAMA psychiatry, 83(3), 306-314","doi":"10.1001/jamapsychiatry.2025.4308","pmid":"41563749","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Preclinical evidence consistently supports GLP-1 RA efficacy across alcohol, nicotine, opioid, and psychostimulant use disorders. Observational human data suggest benefits. RCTs are emerging with promising but mixed signals. No increased psychopathology risk.","whyItMatters":"Addiction causes enormous human suffering with few effective medications. GLP-1 drugs are already widely available and could be rapidly repurposed if RCTs confirm efficacy.","specificNumbers":"","methodology":"Narrative review of preclinical models, observational cohort studies, emerging RCTs, and pharmacovigilance data on GLP-1 therapies for substance use and mental health disorders.","limitations":"Very limited RCT data. Most human evidence is observational. Optimal dose, duration, and individual predictors of response unknown. Mechanisms not fully understood."},{"rthcId":"RPEP-15154","title":"Sea cucumber protein hydrolysate restores the Th1/Th2 paradigm in cyclophosphamide-induced immunosuppressed mice.","authors":"Farooqui, Nabeel Ahmed; Rehman, Ata Ur; Khan, Asif Iqbal; Ullah, Hidayat; Ali, Muhsin; Yousuf, Waleed; Alioui, Yamina; Atta, Aamna; Abusidu, Mohammad; Saleh, Bilal; Ghaleb, Eslam; Li, Yanxia; Xin, Yi; Siddiqui, Nimra Zafar; Wang, Liang","year":2026,"journal":"Frontiers in nutrition, 13, 1758733","doi":"10.3389/fnut.2026.1758733","pmid":"41675385","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"SCPH oral treatment restored Th1/Th2 balance in CYP-immunosuppressed mice, upregulating IFNG, TBX21, IgG, IgM and downregulating IL4, GATA3, IL-10, IgA, sIgA, with improved splenic architecture.","whyItMatters":"Chemotherapy patients need safe ways to restore immune function. Marine-derived bioactive peptides that can be taken orally offer a natural immunonutritional approach.","specificNumbers":"","methodology":"Collagenase-derived sea cucumber protein hydrolysate preparation, CYP-induced immunosuppression in BALB/c mice, oral SCPH treatment, immune organ indices, leukocyte counts, gene expression, serum cytokines/immunoglobulins, and splenic histology/IHC.","limitations":"Mouse model. Specific peptide sequences responsible for immunomodulation not identified. Dose-response not explored. Human clinical evidence needed."},{"rthcId":"RPEP-15155","title":"Cutaneous Adverse Events Associated With GLP-1 Receptor Agonists: A FAERS Database Analysis From 2018-2024.","authors":"Fat, Marisa N; Johnson, Hayden C; Farberg, Aaron S","year":2026,"journal":"Journal of drugs in dermatology : JDD, 25(1), 11-16","doi":"10.36849/JDD.9448","pmid":"41493256","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Cutaneous AEs reported in up to 8.16% of GLP-1 RA cases; semaglutide highest rate, dulaglutide lowest. PRR 0.27 vs DPP-4 inhibitors indicates proportionally fewer skin events. Exenatide showed increased odds (OR 5.01).","whyItMatters":"Skin reactions can affect treatment adherence. Knowing which GLP-1 drugs have better dermatologic profiles helps guide prescribing decisions, especially as indications expand beyond diabetes.","specificNumbers":"","methodology":"Analysis of FDA FAERS data (2018-2024) for semaglutide, liraglutide, exenatide, and dulaglutide, with PRR calculation using DPP-4 inhibitors as comparator and logistic regression for predictors.","limitations":"FAERS has inherent reporting biases. Cannot determine causation. Underreporting likely. Denominator (total prescriptions) not available for true incidence calculation."},{"rthcId":"RPEP-15156","title":"Analytical characterization and stability evaluation of high-purity melittin isolated from crude bee venom via one-step, scalable reversed-phase liquid chromatography.","authors":"Fatahian, Farnaz; Rezadoost, Hassan; Golestan, Seyed Mohammad Jafar Seyed; Behboudi, Hossein; Catani, Martina; Cavazzini, Alberto; Ghassempour, Alireza","year":2026,"journal":"Journal of chromatography. A, 1766, 466605","doi":"10.1016/j.chroma.2025.466605","pmid":"41389519","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"One-step RP-HPLC achieved 99.05% recovery and 98.44% purity for melittin, with 6-month accelerated stability testing (ICH conditions) demonstrating superior stability of purified melittin over crude venom.","whyItMatters":"Pharmaceutical development of melittin-based drugs requires reproducible, high-purity isolation. This method provides the quality needed for drug development and regulatory submissions.","specificNumbers":"","methodology":"RP-HPLC purification, ESI-MS and MALDI-TOF MS identity confirmation, CD spectroscopy for structural integrity, and 6-month ICH accelerated stability testing (40°C, 75% RH).","limitations":"Optimized for Apis mellifera venom; may need adjustment for other bee species. Scale-up economics not addressed. Stability only tested under one set of ICH conditions."},{"rthcId":"RPEP-15157","title":"AI-driven peptide discovery for endometrial cancer: deep generative modeling and molecular simulation in the big data era.","authors":"Fatima, Israr; Rehman, Abdur; Wang, Zhibo; Ur Rehman, Hafeez; Aldaw, Mohamed; Warraich, Dawood Ahmed; Meng, Yuxuan; Li, Yan; Liao, Mingzhi","year":2026,"journal":"Journal of computer-aided molecular design, 40(1), 47","doi":"10.1007/s10822-025-00735-9","pmid":"41524971","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"AI-generated peptide-like molecules showed superior binding to EC targets: AKT1 (-11.53 kcal/mol vs reference -8.50), CTNNB1 (-12.33 kcal/mol), ESR1 (-11.05 kcal/mol), with RMSD <2.5 Å in MD simulations and favorable WaterSwap binding energies (-34 to -37 kcal/mol).","whyItMatters":"Endometrial cancer is the most common gynecologic malignancy. AI-designed peptide-based drugs that outperform existing inhibitors could accelerate therapeutic development.","specificNumbers":"","methodology":"AI generative pipeline (DRL + GANs + VAEs) generating 14,200+ structures, deep learning-enhanced docking, 100 ns molecular dynamics simulations, WaterSwap free energy calculations, and ADMET prediction.","limitations":"Entirely computational; no experimental synthesis or biological testing. Binding predictions may not translate to cellular activity. ADMET predictions are approximate."},{"rthcId":"RPEP-15158","title":"Effect of Oral Glucose Administration on Ghrelin Levels in Normal-Height Prepubertal Children Born Small for Gestational Age (SGA).","authors":"Fedorczak, Anna; Smalczewska, Paula; Grobelna, Magdalena; Szałapska, Małgorzata; Zygmunt, Arkadiusz; Stawerska, Renata","year":2026,"journal":"International journal of molecular sciences, 27(4)","doi":"10.3390/ijms27041791","pmid":"41751928","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Obese SGA children showed lower fasting/post-load ghrelin and smaller suppression. Fasting ghrelin and its suppression were independently associated with HOMA-IR, while post-load ghrelin was determined by post-load insulin.","whyItMatters":"Understanding how ghrelin signaling is disrupted in children at metabolic risk could inform early intervention strategies to prevent childhood obesity and its consequences.","specificNumbers":"","methodology":"Cross-sectional study of 98 prepubertal SGA children (ages 5-9), with anthropometry, blood pressure, fasting lipids, glucose, insulin, and ghrelin at baseline and 120 min during OGTT, with regression analyses.","limitations":"Cross-sectional design; cannot determine causation. Single ghrelin measurement timepoint (120 min). Total ghrelin measured (not acyl vs desacyl). Moderate sample size."},{"rthcId":"RPEP-15159","title":"Analog of prolactin-releasing peptide reduces body weight primarily through sustained fatty acid oxidation rather than hypophagia.","authors":"Feetham, Claire H; Groom, Sam; John, Linu M; Christoffersen, Berit Ostergaard; Collabolletta, Valeria; Lyons, David; Adamson, Antony; Lundh, Sofia; Gerstenberg, Marina Kjærgaard; Tang-Christensen, Mads; Conde-Frieboes, Kilian W; Secher, Anna; Kruse Hansen, Ann Maria; Luckman, Simon M","year":2026,"journal":"Cell metabolism, 38(1), 100-114.e6","doi":"10.1016/j.cmet.2025.10.021","pmid":"41330374","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"NN501 reduced body weight comparably to GLP-1 RAs but with only modest food intake reduction, primarily through increased energy expenditure and fatty-acid oxidation, with more gradual weight regain and no compensatory hyperphagia after discontinuation.","whyItMatters":"Weight regain is the biggest limitation of current GLP-1 drugs. A peptide that maintains weight loss through energy burning rather than appetite suppression could provide more durable results.","specificNumbers":"","methodology":"Preclinical study of NN501 (GPR10/NPFFR2 agonist) in mice, comparing weight loss mechanisms to GLP-1 receptor agonism using body weight, food intake, energy expenditure, fatty-acid oxidation, and post-treatment weight regain assessments.","limitations":"Mouse model only. Human GPR10/NPFFR2 biology may differ. Long-term effects and safety profile unknown. Not tested in combination with GLP-1 drugs."},{"rthcId":"RPEP-15160","title":"Glucagon-Like Peptide-1 Receptor Agonists and Decreased Subarachnoid Hemorrhage Risk in Patients With Intracranial Aneurysm.","authors":"Feghali, James; Ruchika, Fnu; Horowitz, Melanie A; Xu, Risheng; Jackson, Christopher M; Caplan, Justin M; Huang, Judy; Tamargo, Rafael J; Gonzalez, L Fernando","year":2026,"journal":"Stroke, 57(3), 802-807","doi":"10.1161/STROKEAHA.125.053599","pmid":"41492776","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1RA use associated with lower SAH risk (HR 0.66, 95% CI 0.50-0.87) and mortality (HR 0.63, 95% CI 0.52-0.76) in matched diabetic patients with intracranial aneurysms over 5 years, confirmed in untreated aneurysm subgroup.","whyItMatters":"Brain aneurysm management is limited to surgery or observation. A medication that reduces rupture risk could save lives, especially in patients too sick for surgery.","specificNumbers":"","methodology":"Retrospective propensity-matched cohort study using TriNetX global database (2010-2025), matching on 95 variables including smoking and hypertension, with 5-year follow-up and falsification analysis.","limitations":"Retrospective observational design. Only diabetic patients studied. Cannot determine mechanism. GLP-1 users may have better overall health management."},{"rthcId":"RPEP-15161","title":"Rational Design of a Bioconjugated Antitumor Peptide with Tumor-Selective Targeting and Microenvironment-Responsive Activation.","authors":"Feng, Chunlai; Deng, Wen; Cai, Min; Hu, Yujiao; Liang, Wenyan; Dong, Hangyu; Rui, Mengjie","year":2026,"journal":"Pharmaceutical research, 43(1), 123-136","doi":"10.1007/s11095-025-03990-5","pmid":"41372692","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"PBA-AMP showed tumor-selective binding via sialic acid targeting, 3× improved MCF-7 cytotoxicity (IC50 38.46 vs 110 μM), selective tumor accumulation in vivo, and significant tumor suppression in 4T1 mice without systemic toxicity.","whyItMatters":"Making antimicrobial peptides tumor-selective through simple chemical modification opens a new approach to targeted cancer therapy that is simpler and potentially cheaper than antibody-based targeting.","specificNumbers":"","methodology":"Chemical conjugation of PBA to cationic AMP, MD simulations (50 ns), MCF-7 cellular uptake/cytotoxicity assays, in vivo imaging for tumor accumulation, and 4T1 tumor-bearing mouse efficacy study.","limitations":"Mouse model with single tumor type (4T1). IC50 of 38.5 μM is relatively high for clinical drugs. PBA may also bind sialic acid on some normal cells. Pharmacokinetics not fully characterized."},{"rthcId":"RPEP-15162","title":"Recent advances in peptide-drug conjugates as anticancer agents.","authors":"Feng, Yanyan; Li, Tong; Li, Shijia; Liu, Zhouyan; Tang, Ziwei; Chen, Cheng; Zhou, Chen; Lu, Tulin; Chen, Jichao","year":2026,"journal":"European journal of medicinal chemistry, 304, 118482","doi":"10.1016/j.ejmech.2025.118482","pmid":"41418741","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"PDCs enable targeted delivery of cytotoxic payloads via tumor-homing peptides, with PROTAC-based PDCs emerging as a novel approach combining targeted delivery with targeted protein degradation.","whyItMatters":"PDCs offer a simpler, cheaper alternative to antibody-drug conjugates (ADCs) for targeted cancer therapy, and the addition of PROTAC technology could enable unprecedented precision in cancer treatment.","specificNumbers":"","methodology":"Narrative review of PDC design principles, components (tumor-homing peptides, linkers, payloads), recent anticancer applications, and emerging PROTAC-PDC technology.","limitations":"Most PDCs are in preclinical development. In vivo stability and pharmacokinetics remain challenging. Clinical data is limited. Manufacturing scale-up for complex conjugates is non-trivial."},{"rthcId":"RPEP-15163","title":"Real-world effectiveness and safety of galcanezumab for the treatment of migraine: A systematic review and meta-analysis.","authors":"Fernández-Bravo-Rodrigo, Jaime; Pascual-Morena, Carlos; Saz-Lara, Alicia; Martínez-García, Irene; Lever-Megina, Carla Geovanna; Patiño-Cardona, Silvana; Flor-García, Amparo; Cavero-Redondo, Iván","year":2026,"journal":"Headache, 66(1), 262-277","doi":"10.1111/head.70003","pmid":"41246917","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"At 1 month: MMD reduction -6.93 days, HIT reduction -7.96 points. Over 60% achieved ≥50% MMD/MHD reduction within 3 months. Effects gradually increased through 12 months. AE rates 25% (6 months) to 35% (12 months).","whyItMatters":"Real-world data confirms galcanezumab works outside of ideal trial conditions, giving clinicians and patients confidence in this anti-CGRP therapy.","specificNumbers":"","methodology":"Systematic review and meta-analysis of 36 real-world studies from PubMed, Scopus, and Web of Science through February 2025, with pooled proportions and mean differences.","limitations":"Significant heterogeneity across studies. No randomization or control groups in most studies. Potential publication bias. Variable outcome measurement across studies."},{"rthcId":"RPEP-15164","title":"Stress-type specific changes of VIP signaling in limbic regions of the rat brain.","authors":"Ferro, Federico; Fontebasso, Veronica; Basille-Dugay, Magali; Vaudry, David; Ebner, Karl","year":2026,"journal":"Neuroscience letters, 870, 138430","doi":"10.1016/j.neulet.2025.138430","pmid":"41177440","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Acute stress increased VIP 200% in CeA and 350% in MeA, with VPAC1/2 upregulation across limbic regions. Chronic stress upregulated VPAC1 in PVN (120%) and VPAC2 in CeA (280%) with slight VIP downregulation, revealing stress-duration-dependent plasticity.","whyItMatters":"Understanding how stress remodels neuropeptide signaling could reveal new targets for treating anxiety disorders, PTSD, and chronic stress-related conditions.","specificNumbers":"","methodology":"qRT-PCR analysis of VIP, VPAC1, and VPAC2 expression in specific limbic brain regions (CeA, MeA, BLA, PVN, BNST) of Sprague-Dawley rats after acute forced swim or chronic unpredictable stress.","limitations":"Rat model; human VIP stress responses may differ. Only measured mRNA, not protein levels. Two stress paradigms may not capture all stress types. Male rats only."},{"rthcId":"RPEP-15165","title":"Weight Loss With SGLT2 Inhibitors, Semaglutide, and Transcranial Magnetic Stimulation in Type 2 Diabetes and Obesity.","authors":"Ferrulli, Anna; Senesi, Pamela; Sonaglioni, Andrea; Cannavaro, Daniele; Massarini, Stefano; Macrì, Concetta; Cipponeri, Elisa; DeFronzo, Ralph A; Luzi, Livio","year":2026,"journal":"Obesity (Silver Spring, Md.), 34(2), 317-322","doi":"10.1002/oby.70105","pmid":"41451880","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"At 12 months: rTMS -8.2 ± 1.0 kg, semaglutide 0.5 mg -5.7 ± 0.9 kg (not significantly different), SGLT2i -2.0 ± 0.7 kg (significantly less than both, p<0.01). rTMS and semaglutide showed progressive weight loss; SGLT2i showed regain after 6 months.","whyItMatters":"rTMS is a non-pharmacological option that may complement or substitute for GLP-1 drugs in patients who can't tolerate them, offering sustained weight loss without medication side effects.","specificNumbers":"","methodology":"Retrospective comparative analysis of 107 patients with T2D and obesity: 40 on SGLT2i, 37 on semaglutide 0.5 mg, 30 on rTMS (3×/week for 5 weeks), all with dietary advice, followed for 12 months.","limitations":"Retrospective non-randomized design. Semaglutide used at low dose (0.5 mg). Small groups. rTMS protocol (5 weeks) differs fundamentally from ongoing drug therapy. Not blinded."},{"rthcId":"RPEP-15166","title":"Total Chemical Synthesis and Evaluation of the Antimicrobial Properties of Porcine β-Defensin 5 Against Gram-Positive and Gram-Negative Bacteria.","authors":"Finatto, Arthur Nery; Nguyen, Vy; Nguyen, Phuong Trang; Bourgault, Steve; de Oliveira Costa, Matheus","year":2026,"journal":"Probiotics and antimicrobial proteins","doi":"10.1007/s12602-025-10870-2","pmid":"41779113","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Fully synthesized pBD-5 showed dose-dependent antimicrobial activity with significant growth reductions at 25 μM (OD) and 100 μM (CFU: 2-log reduction for S. epidermidis, 1-log for E. coli), with hemolysis only at 240 μM.","whyItMatters":"Successfully synthesizing a complex defensin with all disulfide bonds confirms it can be produced for pharmaceutical development and validates its antimicrobial activity.","specificNumbers":"","methodology":"Orthogonal protection strategy for disulfide bond formation, CD spectroscopy for structure, paired MIC assays at 8 concentrations (1.56-200 μM) against E. coli and S. epidermidis with OD600 and CFU confirmation, and hemolysis assays.","limitations":"Modest antimicrobial potency compared to some other AMPs. Only tested against two bacterial species. In vivo efficacy not assessed. Synthesis may be costly at scale."},{"rthcId":"RPEP-15167","title":"Oxytocin receptor antagonism in migraine: a randomized, double-blind, placebo-controlled provocation study.","authors":"Fitzek, Mira Pauline; Kleist, Paula; Handtmann, Cleo; Overeem, Lucas Hendrik; Hoehne, Carolin Luisa; Lange, Kristin Sophie; Angerhöfer, Cornelius; Salim, Yones; Ebert, Andreas D; Mattern, Nicole; Reuter, Uwe; Raffaelli, Bianca","year":2026,"journal":"The journal of headache and pain, 27(1)","doi":"10.1186/s10194-026-02297-z","pmid":"41699456","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Atosiban did not increase migraine-like attacks vs placebo in women with migraine (30% vs 20%, p=0.75), healthy controls (0% vs 0%), or men with migraine (10% vs 15%, p>0.999). Vascular changes occurred in controls but not migraine patients.","whyItMatters":"Understanding that oxytocin blockade doesn't trigger migraine clarifies its role in the disease and informs therapeutic strategy—intranasal oxytocin may work through modulation rather than correcting a deficiency.","specificNumbers":"","methodology":"Randomized, double-blind, placebo-controlled, crossover study in 60 participants (20 WM, 20 HC, 20 MM) receiving atosiban IV or placebo, with 12-hour observation for migraine attacks and vascular measurements.","limitations":"Atosiban is short-acting and may not penetrate the brain significantly. Stable hormonal conditions (continuous contraception) may not reflect natural hormonal fluctuations. Three-hour infusion may be insufficient."},{"rthcId":"RPEP-15168","title":"Functionalized peptide hydrogel to generate human insulin-producing cells in vitro.","authors":"Flores-Ibarra, Brandhon F; Enríquez-Rodríguez, Andrea I; Robles-Pablos, Kimberly P; Rodas-Junco, Beatriz A; Argüelles-Monal, Waldo M; Silva-Gutiérrez, Luisa L; Pérez-González, Refugio; Patrón-Soberano, Olga A; Rochín-Wong, Carmen S; Castillo-Díaz, Luis A","year":2026,"journal":"Journal of bioscience and bioengineering, 141(3), 185-193","doi":"10.1016/j.jbiosc.2025.11.007","pmid":"41436341","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"ECM-FEK9 peptide hydrogel adopted β-sheet nanofiber structure, maintained cell viability, and supported differentiation of hDPSCs into IPCs expressing PDX-1, Glut-2, and producing insulin within 10 days of 3D culture.","whyItMatters":"Generating insulin-producing cells from accessible stem cells (dental pulp) in a peptide gel could eventually replace pancreatic islet transplantation for type 1 diabetes, avoiding donor shortages.","specificNumbers":"","methodology":"FEK9 peptide hydrogel functionalization with RGD/GFOGER/IKVAV, structural characterization (FTIR, rheology), 3D culture of hDPSCs with directed induction, and assessment by confocal microscopy (β-cell markers) and spectrophotometry (insulin).","limitations":"In vitro study. Insulin production levels not quantified relative to native β-cells. Functional glucose-responsive insulin secretion not tested. Long-term cell stability unknown."},{"rthcId":"RPEP-15169","title":"Glucagon-Like Peptide-1: The Role of Calcium in Gut-Glucose Axis.","authors":"Foamkom, Astrid-Ines; Abdelhady, Hosam G; Razzaque, Mohammed S","year":2026,"journal":"Advances in experimental medicine and biology, 1493, 127-131","doi":"10.1007/978-3-032-04357-3_10","pmid":"41219603","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Extracellular calcium triggers GLP-1 exocytosis from L-cells through CaSR and voltage-gated calcium channels, positioning calcium as an essential signaling ion in the gut-glucose endocrine axis.","whyItMatters":"Understanding the calcium-GLP-1 connection could lead to nutritional strategies or drugs that boost natural GLP-1 release, potentially complementing GLP-1 drug therapy.","specificNumbers":"","methodology":"Review chapter summarizing recent studies on calcium's role in GLP-1 secretion, covering CaSR signaling, voltage-gated calcium channels, and intracellular calcium dynamics in L-cells.","limitations":"Review chapter without new data. Mechanisms primarily from cell culture and animal studies. Human L-cell calcium signaling may differ. Dietary calcium's effect on in vivo GLP-1 levels needs more study."},{"rthcId":"RPEP-15170","title":"GLP-1 receptor agonist treatment in women with polycystic ovary syndrome - a systematic review and meta-analysis.","authors":"Forslund, Maria; Wändell, Per; Forsberg, Lisa; Österberg, Marie; Dagerhamn, Jessica; Wernersson, Emma; Kärrman Fredriksson, Maja; Ringborg, Anna; Lindén Hirschberg, Angelica","year":2026,"journal":"European journal of endocrinology","doi":"10.1093/ejendo/lvag033","pmid":"41701618","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RAs as add-on therapy reduced BMI by -1.38 kg/m² (95% CI -2.39 to -0.38; low certainty) in PCOS women. No significant differences for LDL, triglycerides. Insufficient evidence for glucose, insulin, hirsutism, menstrual regularity.","whyItMatters":"PCOS is the most common endocrine disorder in reproductive-age women. Understanding what GLP-1 drugs can and cannot do for PCOS guides clinical decision-making.","specificNumbers":"","methodology":"Systematic review and meta-analysis of 11 RCTs from Cochrane, EMBASE, and Medline (searched September 2024), registered in PROSPERO CRD42024535096.","limitations":"Low certainty evidence overall. Most trials were short-term. No assessment of quality of life or reproductive outcomes in sufficient numbers. Heterogeneity in study designs."},{"rthcId":"RPEP-15171","title":"Pharmacological Management of Obesity in Pregnancy: A Review of Current and Emerging Therapies.","authors":"Fotheringham, Penelope; McGee, Richard G; Chang, Ruby; Kennedy, Debra; Simmons, David","year":2026,"journal":"Drugs, 86(3), 321-333","doi":"10.1007/s40265-025-02279-6","pmid":"41619150","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RAs are not recommended in pregnancy, but large human observational studies have not demonstrated significant independent risk of major congenital malformations after controlling for confounding maternal comorbidities.","whyItMatters":"With millions of women of reproductive age taking GLP-1 drugs, understanding pregnancy safety is urgent—both for planned pregnancies and accidental exposures.","specificNumbers":"","methodology":"Systematic literature search evaluating historical and emerging obesity pharmacotherapies for pregnancy, with focus on safety and efficacy data for GLP-1 receptor agonists.","limitations":"No RCTs of GLP-1 drugs in pregnancy exist. Observational data has inherent confounding. Fetal exposure timing and duration effects unknown. Animal-to-human extrapolation uncertain."},{"rthcId":"RPEP-15172","title":"Effect of lixisenatide on arterial stiffness in people with type 2 diabetes and kidney disease: Results of a randomised controlled trial.","authors":"Fountoulakis, Nikolaos; Pavlou, Panagiotis; Stathi, Dimitra; Goubar, Aicha; Corcillo, Antonella; Flaquer, Maria; Ayis, Salma; Gnudi, Luigi; Karalliedde, Janaka","year":2026,"journal":"Diabetes, obesity & metabolism","doi":"10.1111/dom.70481","pmid":"41705420","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Lixisenatide did not significantly change Ao-PWV (9.65 vs 9.96 m/s, p=0.38), albuminuria, or Klotho levels compared to placebo after 24 weeks, despite HbA1c improvement, in T2D patients with CKD.","whyItMatters":"Understanding why some GLP-1 drugs don't protect the heart and kidneys as well as others helps optimize drug selection for high-risk patients.","specificNumbers":"","methodology":"Single-center, randomized, double-blind, parallel-group, placebo-controlled trial (ISRCTN97699312) with 101 participants (47 lixisenatide, 43 evaluable placebo) over 24 weeks.","limitations":"Single-center, small study. 24 weeks may be too short for vascular remodeling. Lixisenatide is short-acting which limits comparison to longer-acting agents."},{"rthcId":"RPEP-15173","title":"Targeting cardiometabolic risk in type 1 diabetes through incretin physiology.","authors":"Frampton, Ruth; Hocking, Samantha; Snaith, Jennifer R; Greenfield, Jerry R","year":2026,"journal":"Trends in endocrinology and metabolism: TEM, 37(2), 135-150","doi":"10.1016/j.tem.2025.06.004","pmid":"40610267","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"T1D involves dysfunctional GIP, GLP-1, and glucagon signaling that contributes to dysglycemia and cardiovascular risk, with semaglutide and tirzepatide emerging as potential therapeutic options targeting these specific metabolic deficits.","whyItMatters":"T1D patients have no approved incretin-based therapies despite clear metabolic rationale. Demonstrating cardiovascular benefits could expand GLP-1 drug indications to T1D.","specificNumbers":"","methodology":"Narrative review of incretin hormone physiology in T1D, focusing on GIP, GLP-1, and glucagon dysfunction and emerging therapeutic opportunities with incretin-based drugs.","limitations":"Mostly conceptual/review without new data. Clinical trials of GLP-1 drugs in T1D for cardiovascular outcomes are limited. Dosing and safety in T1D need separate validation."},{"rthcId":"RPEP-15174","title":"Efficacy and safety of rimegepant 75 mg orally disintegrating tablet for the acute treatment of chronic rhinosinusitis in adults: Results from a multicenter, randomized, placebo-controlled, phase 2/3 trial.","authors":"Franjic, Daniel; Fountaine, Robert J; Nalpas, Catherine; Goswami, Budhaditya; Fullerton, Terence","year":2026,"journal":"PloS one, 21(3), e0342907","doi":"10.1371/journal.pone.0342907","pmid":"41779821","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"No significant treatment differences between rimegepant and placebo for primary (facial pain NRS, -0.1 [95% CI -0.7 to 0.5]) or secondary outcomes (nasal congestion, discharge, TNSS, headache relief, rescue medication use).","whyItMatters":"This negative result is informative: despite biological plausibility, CGRP blockade does not appear to help CRS. This narrows the therapeutic scope of anti-CGRP drugs and redirects CRS research.","specificNumbers":"","methodology":"Double-blind, randomized, placebo-controlled, phase 2/3 trial (NCT05248997) with 261 adults with CRS (131 rimegepant, 130 placebo), stratified by nasal polyp status.","limitations":"Single-dose design may be insufficient. CRS is a chronic condition that may need sustained treatment. Small evaluable sample (96 vs 100). CGRP's role in CRS may require different intervention strategies."},{"rthcId":"RPEP-15175","title":"Decoding antimicrobial peptides: An insight into their discovery, classifications, structures, and applications.","authors":"Fu, Qifu; Yan, Bohu; Xu, Jialin; Ding, Yuqi; Chen, Xiaojun; Wang, Yanan; Sun, Zhiliang; Li, Jiyun","year":2026,"journal":"Microbial pathogenesis, 214, 108421","doi":"10.1016/j.micpath.2026.108421","pmid":"41780769","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Most AMPs fail clinically due to pharmacokinetic limitations, dosing constraints, and indication selection rather than lack of antimicrobial activity, with AI-guided design improving discovery but not yet solving the in vitro-to-in vivo efficacy gap.","whyItMatters":"Understanding why AMPs fail clinically is essential for designing ones that succeed. This review provides a framework for translating promising lab compounds into real drugs.","specificNumbers":"","methodology":"Comprehensive review integrating mechanistic insights, clinical trial outcomes (successes and failures), pharmacokinetic considerations, and evaluation of computational/AI-guided AMP design platforms.","limitations":"Cannot cover all AMP candidates comprehensively. Some failures may have unreported details. AI tools are evolving rapidly and conclusions may soon be outdated."},{"rthcId":"RPEP-15176","title":"Beyond metabolism: sexual dysfunction and weight-loss drugs.","authors":"Fuentes-Mendoza, Jenyfer M; Concepción-Zavaleta, Marcio J; Mendoza-Godoy, Jeny J; Concepción-Urteaga, Luis; Paz-Ibarra, José; Coronado-Arroyo, Julia C","year":2026,"journal":"Sexual medicine reviews, 14(1)","doi":"10.1093/sxmrev/qeaf074","pmid":"41427954","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RAs improve erectile function, testosterone, and sperm parameters in men. Tirzepatide case reports suggest potential sexual side effects. Setmelanotide demonstrates melanocortin pathway involvement in sexual function. Sexual outcomes are underrepresented as trial endpoints.","whyItMatters":"Sexual dysfunction affects quality of life as much as many chronic diseases. Understanding how weight loss drugs affect sexual health helps clinicians counsel patients and design better trials.","specificNumbers":"","methodology":"Narrative review of PubMed, Scopus, and Embase for studies reporting sexual outcomes (FSFI, IIEF, or clinical reports) related to obesity pharmacotherapies.","limitations":"Most evidence is secondary outcomes or case reports. Sex-specific data extremely limited for women. Cannot distinguish direct drug effects from weight loss effects. Validated sexual function measures rarely used."},{"rthcId":"RPEP-15177","title":"Predicting Long-Term Weight Loss Using Self-Reported, Digitally Collected, Real-World Data After Initiation of Semaglutide for Overweight or Obesity.","authors":"Færch, Kristine; Gomes, Mikel M; Bramming, Maja; Sørensen, Mads R; Strathe, Anders","year":2026,"journal":"Advances in therapy","doi":"10.1007/s12325-026-03507-5","pmid":"41718940","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The prediction algorithm accurately forecast individual weight loss in real-world semaglutide users with bias of 0.7-1.4 kg at 6 months and -0.6 to 0.6 kg at 1 year, with AUC 0.74-0.95 for categorical weight loss prediction.","whyItMatters":"Personalized weight loss predictions could help patients set realistic goals and help clinicians identify early non-responders who might benefit from treatment adjustment.","specificNumbers":"","methodology":"Application of exposure-response weight prediction model (from semaglutide RCTs) to 1,797 WegovyCare app users, with model validation at multiple timepoints using self-reported dosing and body weight.","limitations":"Self-reported data may be inaccurate. App users are self-selected (likely more motivated). 81% women limits generalizability. Algorithm assumes consistent dosing adherence."},{"rthcId":"RPEP-15178","title":"CagriSema Versus Semaglutide Monotherapy or Placebo for Obesity: A Systematic Review and Meta-Analysis of Randomized Controlled Trials with GRADE Assessment.","authors":"Gadelmawla, Ahmed Farid; Hammad, Noha; Atta, Karim; Diaa, Ahmed; Abouzkaly, Fatma; Soni, Kriti; Kelkar, Raveena; Agrawal, Siddharth P; Ahmed, Raheel; Jain, Hritvik; Passey, Siddhant; Aronow, Wilbert S","year":2026,"journal":"The American journal of cardiology","doi":"10.1016/j.amjcard.2026.02.030","pmid":"41759565","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CagriSema vs comparators: additional -11 kg weight, -9.41 cm waist, -7.06 mmHg systolic BP. Cohen's d for weight: -1.38. GI adverse events 32% more frequent (RR 1.32). 4 RCTs, n=4,419.","whyItMatters":"If validated long-term, CagriSema could become the most effective obesity drug available, addressing a key unmet need for patients who don't lose enough weight on GLP-1 monotherapy.","specificNumbers":"","methodology":"Systematic review and meta-analysis of 4 RCTs from MEDLINE, Web of Science, Scopus, and Cochrane Library through July 2025, with GRADE assessment.","limitations":"High heterogeneity (I²=94.8%). Only 4 RCTs available. Long-term outcomes unknown. GI tolerability may limit real-world effectiveness. Cost may restrict access."},{"rthcId":"RPEP-15179","title":"Discovery of Encrypted Peptides in a Human Matrix Metallopeptidase.","authors":"Gaglione, Rosa; Schibeci, Martina; Piccolo, Erika; Culurciello, Rosanna; Zannella, Carla; Mensitieri, Francesca; Dal Piaz, Fabrizio; Cafaro, Valeria; De Filippis, Anna; Pizzo, Elio; Notomista, Eugenio; Torres, Marcelo D T; de la Fuente-Nunez, Cesar; Arciello, Angela","year":2026,"journal":"JACS Au, 6(1), 124-143","doi":"10.1021/jacsau.5c00947","pmid":"41614195","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Three EPs from MMP-19 showed broad-spectrum antimicrobial activity (including MDR strains), antibiofilm, antiviral, LPS-neutralizing, and synergistic properties, with no resistance development and in vivo efficacy in a murine skin infection model.","whyItMatters":"Finding potent antimicrobials hidden in our own proteins means the human body has an untapped reservoir of anti-infective peptides that are inherently compatible with human biology.","specificNumbers":"","methodology":"Peptide identification from MMP-19 sequence, antimicrobial and antiviral assays, membrane depolarization/permeabilization studies, biofilm assays, synergy testing, serial passaging for resistance, D-amino acid analog synthesis, and murine skin infection model.","limitations":"Only one protein (MMP-19) mined. In vivo testing limited to skin infection. Pharmacokinetics and systemic efficacy unknown. D-amino acid analogs are expensive to produce at scale."},{"rthcId":"RPEP-15180","title":"Pharmacological Management of Diabesity: Current and Emerging Therapies.","authors":"Galasso, Martina; Caporusso, Mariangela; Volatile, Alessandra; Verde, Ludovica; Esposito, Katherine; Giorgino, Francesco; Perrini, Sebastio; Colao, Annamaria; Barrea, Luigi; Muscogiuri, Giovanna","year":2026,"journal":"Current obesity reports, 15(1), 5","doi":"10.1007/s13679-025-00681-5","pmid":"41528611","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"SGLT2i, GLP-1 RAs, and emerging dual/triple agonists offer complementary mechanisms for diabesity management, with clinical evidence supporting progressive pharmacological intensification.","whyItMatters":"Diabesity affects hundreds of millions globally. Understanding the full pharmacological toolkit enables optimal treatment selection and combination strategies.","specificNumbers":"","methodology":"Comprehensive narrative review of clinical evidence for SGLT2i, GLP-1 RAs, and multi-receptor agonists in diabesity management.","limitations":"Broad review may lack depth on individual drugs. Rapidly evolving field means some information may be superseded quickly."},{"rthcId":"RPEP-15181","title":"Proteomic and Functional Characterization of Antimicrobial Peptides Derived from Fisheries Bycatch via Enzymatic Hydrolysis.","authors":"Galendi, Vicky Balesteros S Blumen; Coelho, Guilherme Rabelo; Murback, Letícia; Valenti, Wagner C; Camargo, Tavani Rocha; Franzolin, Marcia Regina; Pimenta, Daniel Carvalho; Ferreira, Rui Seabra","year":2026,"journal":"Marine drugs, 24(1)","doi":"10.3390/md24010036","pmid":"41590733","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Proteomic analysis of fisheries bycatch identified novel antimicrobial peptides with broad-spectrum activity including against drug-resistant bacterial strains.","whyItMatters":"Converting fisheries waste into antimicrobial peptide leads addresses both ecological waste and the antibiotic resistance crisis simultaneously.","specificNumbers":"","methodology":"Proteomic characterization of bycatch species, peptide identification and purification, antimicrobial activity testing against standard and drug-resistant strains.","limitations":"In vitro activity only. Specific peptide sequences and potencies need full characterization. Scalability of bycatch-based peptide production uncertain."},{"rthcId":"RPEP-15182","title":"Enteroendocrine hormonal response after the ingestion of cola beverages with sucrose and non-nutritive sweeteners in healthy adults: A randomized crossover trial.","authors":"Galicia-Ayala, César; Klünder-Klünder, Miguel; Vilchis-Ordoñez, Armando; López-Martínez, Briceida; Miranda-Lora, América L","year":2026,"journal":"Nutrition (Burbank, Los Angeles County, Calif.), 141, 112938","doi":"10.1016/j.nut.2025.112938","pmid":"41016269","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"SUC/STE beverage produced glucose-lowering (-12.5 mg/dL at 60 min, p<0.05) and sustained PP increase (+73.4 pg/mL at 120 min, p<0.05). AAK showed no significant hormonal effects vs control.","whyItMatters":"Understanding how different sweeteners affect gut peptide hormones informs dietary recommendations and beverage formulation for metabolic health.","specificNumbers":"","methodology":"Randomized crossover trial in 20 adults with 4 beverages (carbonated water, aspartame/acesulfame K, sucrose/stevia, sucrose), 7-day washouts, measuring glucose, insulin, glucagon, GIP, PP, leptin, and ghrelin at 0-120 min.","limitations":"Small sample (n=20). Acute effects only. Cannot determine if stevia or the reduced sugar content drove the effects. PP increase mechanism unclear."},{"rthcId":"RPEP-15183","title":"Insights into the Mechanism of Action of Tirzepatide: A Narrative Review.","authors":"Galindo, Rodolfo J; Cheng, Alice Y Y; Longuet, Christine; Ai, Minrong; Coskun, Tamer; Malik, Raleigh; Peleshok, Jennifer; Levine, Joshua A; Dunn, Julia P","year":2026,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 17(1), 19-40","doi":"10.1007/s13300-025-01804-w","pmid":"41196501","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tirzepatide's dual GIP/GLP-1 receptor agonism provides comprehensive metabolic benefits across glycemic control, weight loss, cardiorenal protection, and lipid metabolism, with expanding indications to HFpEF and MASH.","whyItMatters":"Tirzepatide is the fastest-growing diabetes/obesity drug. Understanding its dual mechanism helps clinicians maximize its therapeutic potential.","specificNumbers":"","methodology":"Narrative review of tirzepatide mechanism of action, pharmacology, and clinical trial evidence across approved and investigational indications.","limitations":"Review; no new data. Some indications still investigational. Long-term safety data accumulating."},{"rthcId":"RPEP-15184","title":"Glucagon-Like Peptide-1 Receptor Agonists and Chronic Cough.","authors":"Gallagher, Tyler J; Razura, Diego E; Li, Albert; Kim, Ian; Vukkadala, Neelaysh; Barbu, Anca M","year":2026,"journal":"JAMA otolaryngology-- head & neck surgery, 152(2), 163-171","doi":"10.1001/jamaoto.2025.4181","pmid":"41296333","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RA use associated with chronic cough: aHR 1.12 vs all non-GLP-1 drugs; 1.18 vs DPP-4i; 1.32 vs sulfonylureas. After excluding GERD: aHR 1.29 vs all; 1.36 vs DPP-4i; 1.14 vs SGLT2i; 1.25 vs sulfonylureas.","whyItMatters":"With millions taking GLP-1 drugs, even a modest cough risk affects many patients. Identifying this association helps clinicians recognize and manage this underappreciated side effect.","specificNumbers":"","methodology":"Large multicenter cohort study using US EMR data (2005-2025, 70 organizations), propensity-matched comparisons of 427,555 GLP-1 users vs 1,614,495 other second-line diabetes drug users, with Cox regression.","limitations":"Observational design. Cannot prove causation. Chronic cough has many potential causes. ICD coding may not perfectly capture chronic cough."},{"rthcId":"RPEP-15185","title":"68Ga/211At-Labeled Specific NPY1R Peptide-Based Molecular Probe for Glioma-Targeted Imaging and Alpha Therapy.","authors":"Gan, Rong; Xu, Duling; Liu, Weihao; Liu, Jiadi; Yang, Yuanyou; Liu, Ning; Zhang, Qiyue; Wang, Zhimin; Li, Hongyan","year":2026,"journal":"Biomacromolecules, 27(2), 1196-1209","doi":"10.1021/acs.biomac.5c01407","pmid":"41607110","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A 68Ga/211At-labeled NPY1R-targeting peptide demonstrated specific glioma uptake for PET imaging and therapeutic alpha-particle delivery, establishing a theranostic platform for brain tumors.","whyItMatters":"Gliomas have poor prognosis. A peptide that can both diagnose and treat brain tumors through the same receptor target could improve outcomes by enabling precise, personalized therapy.","specificNumbers":"","methodology":"Peptide synthesis and radiolabeling with 68Ga and 211At, binding affinity assays, biodistribution studies, PET imaging, and therapeutic efficacy assessment in glioma models.","limitations":"Preclinical study. Alpha-particle therapy dosimetry in brain is complex. Blood-brain barrier penetration in humans needs confirmation."},{"rthcId":"RPEP-15186","title":"Bidirectional interplay between the gut microbiota and GLP-1 receptor agonists: towards Microbiome-Mediated therapeutics in type 2 diabetes mellitus.","authors":"Ganamurali, Nila; Sabarathinam, Sarvesh","year":2026,"journal":"Journal of diabetes and metabolic disorders, 25(1), 44","doi":"10.1007/s40200-025-01834-y","pmid":"41613163","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Beneficial gut microbes (Akkermansia, Bacteroides, SCFA producers) enhance GLP-1 RA efficacy, while dysbiosis with LPS-producing bacteria correlates with poor response. GLP-1 RAs also beneficially modulate gut microbiota composition.","whyItMatters":"Personalizing GLP-1 therapy based on gut microbiome composition could transform diabetes care, moving from one-size-fits-all to precision prescribing.","specificNumbers":"","methodology":"Brief narrative review of current evidence on GLP-1 RA-gut microbiota bidirectional interactions, focusing on microbial determinants of drug response.","limitations":"Most evidence is correlative. Causation between specific microbes and drug response not established. Microbiome testing is not yet standardized for clinical use."},{"rthcId":"RPEP-15187","title":"The Triple-Agonist Revolution: Retatrutide and the Paradigm Shift in Multi-Hormonal Pharmacotherapy for Obesity and Cardiometabolic Comorbidities.","authors":"Ganamurali, Nila; Sabarathinam, Sarvesh","year":2026,"journal":"Clinical pharmacology in drug development, 15(1), e70001","doi":"10.1002/cpdd.70001","pmid":"41545327","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Retatrutide (triple GLP-1R/GIPR/GcgR agonist) represents a paradigm shift by combining appetite suppression, insulin sensitization, and energy expenditure enhancement in a single molecule for obesity treatment.","whyItMatters":"Current weight loss drugs work mainly through appetite suppression. Adding energy expenditure via glucagon could produce more durable weight loss and address the main limitation of GLP-1 therapy.","specificNumbers":"","methodology":"Narrative review of retatrutide mechanism, preclinical and clinical evidence, and comparison with current GLP-1 and dual agonist therapies.","limitations":"Limited long-term clinical data. Cardiovascular safety of glucagon agonism needs monitoring. Phase 3 results pending."},{"rthcId":"RPEP-15188","title":"Semaglutide Effects on Insulin Sensitivity and β-Cell Function in Patients With Schizophrenia, Prediabetes, and Obesity Treated With Second-Generation Antipsychotics: Findings From the HISTORI Trial, a 30-Week Randomized, Placebo-Controlled Trial With Semaglutide 1.0 mg Weekly.","authors":"Ganeshalingam, Ashok A; Uhrenholt, Nicolai; Arnfred, Sidse; Gæde, Peter; Pedersen, Andreas K; Bilenberg, Niels; Frystyk, Jan","year":2026,"journal":"Diabetes care","doi":"10.2337/dc25-2041","pmid":"41778920","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide reduced fasting glucose (-0.87 mmol/L, p<0.001), improved insulin sensitivity (p=0.001), reduced insulin resistance (p=0.006), and achieved 9.2 kg weight loss. Weight loss mediated insulin sensitivity (p=0.01) and resistance (p=0.01) improvements.","whyItMatters":"Schizophrenia patients lose 15-20 years of life expectancy, largely from metabolic disease caused by their medications. Semaglutide directly addresses this life-threatening side effect.","specificNumbers":"","methodology":"30-week double-blind RCT (NCT05193578) with 154 participants randomized to semaglutide (n=77) or placebo (n=77), 91.5% completion rate, assessing metabolic parameters with mediation analysis for weight loss.","limitations":"Single semaglutide dose (titrated to 1.0 mg or max tolerated). 30-week duration. β-cell function did not improve. Psychiatric outcomes not primary endpoints."},{"rthcId":"RPEP-15189","title":"Cardiac autonomic neuropathy in patients with SGA-treated schizophrenia: a randomized controlled trial of 30 weeks' treatment with semaglutide.","authors":"Ganeshalingam, Ashok Ainkaran; Uhrenholt, Nicolai Gundtoft; Arnfred, Sidse; Gæde, Peter; Pedersen, Andreas Kristian; Bilenberg, Niels; Frystyk, Jan","year":2026,"journal":"Cardiovascular diabetology. Endocrinology reports, 12(1), 2","doi":"10.1186/s40842-025-00258-0","pmid":"41555458","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CAN prevalence: 84% (50% definite) in schizophrenia patients on antipsychotics. CAN correlated with BMI (p<0.05 from BMI 30+) and clozapine. Semaglutide reduced BMI but did not change CAN status over 30 weeks (p=0.516).","whyItMatters":"The 84% CAN prevalence reveals a hidden cardiovascular catastrophe in schizophrenia patients that may explain their excess cardiac mortality. Understanding it doesn't resolve quickly despite weight loss is clinically important.","specificNumbers":"","methodology":"Pre-specified analysis from a 30-week double-blind RCT (NCT05193578) with 154 schizophrenia patients (141 completers), assessing CAN prevalence, correlates, and semaglutide effects on CAN.","limitations":"30 weeks may be too short for nerve regeneration. CAN measurement methods may lack sensitivity to early improvements. Cannot separate antipsychotic-induced from obesity-induced CAN."},{"rthcId":"RPEP-15190","title":"20(S/R)-ginsenoside Rh1 improves type 2 diabetes via gut microbiota-modulated bile acid signaling and FXR/TGR5-dependent GLP-1 enhancement.","authors":"Gao, Ge; Wang, Enyu; Yang, Ge; Gao, Yansong; Zhao, Zijian; Zhao, Yujuan; Kang, You; Zhao, Lei; Li, Shengyu","year":2026,"journal":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 195, 118997","doi":"10.1016/j.biopha.2026.118997","pmid":"41546911","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Rh1 upregulated CYP27A1/CYP7B1, reshaped gut microbiota BSH/bai genes, increased ileal T-β-MCA (FXR suppression) and LCA (TGR5 activation), promoting L-cell differentiation and GLP-1 secretion via CREB/cAMP/GCG/PCSK1 pathway.","whyItMatters":"Understanding how natural compounds boost GLP-1 through specific gut-liver-hormone pathways could lead to nutraceuticals that complement pharmaceutical GLP-1 therapy.","specificNumbers":"","methodology":"HFD/STZ-induced T2DM mouse model treated with 60 mg/kg/day ginsenoside Rh1 for 4 weeks, with 16S rRNA sequencing, targeted bile acid metabolomics, Western blotting, gene expression, and enzyme activity assays.","limitations":"Mouse model. 4-week treatment is short. The specific ginsenoside Rh1 epimers may have different activities. Human gut microbiome responses may differ."},{"rthcId":"RPEP-15191","title":"Disulfide-bonded YC18: A membrane-targeting peptide with superior efficacy against Staphylococcus aureus infections.","authors":"Gao, Jinai; Wang, Yi; Wang, Wanting; Yang, Min; Cao, Kaixun; Pan, Qi; Guo, Ruiyin; Lu, Qiumin; Zhang, Chengchen; Li, Juan; Lai, Ren","year":2026,"journal":"Bioorganic chemistry, 168, 109322","doi":"10.1016/j.bioorg.2025.109322","pmid":"41353928","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"YC18 showed MIC 6.25 μg/mL against S. aureus, no resistance after 35 passages, selective PG membrane targeting, dual-disulfide stability (Cys2-Cys15, Cys6-Cys11), high plasma stability, low cytotoxicity, and in vivo efficacy.","whyItMatters":"S. aureus infections including MRSA cause enormous morbidity. A peptide that bacteria can't become resistant to could be a game-changing antibiotic.","specificNumbers":"","methodology":"cDNA library screening from C. liboensis venom, MIC assays, 35-passage resistance development study, structural prediction and analog studies, MD simulations for membrane interaction, plasma stability, cytotoxicity, and murine infection models.","limitations":"Tested primarily against S. aureus; broader spectrum needs assessment. In vivo testing limited. Manufacturing costs for disulfide-bonded peptides may be high."},{"rthcId":"RPEP-15192","title":"Combination of GLP-1 receptor agonist and Akkermansia muciniphila Akk11 reduces adiposity and ameliorates MASLD in T2D mice.","authors":"Gao, Kaige; Yin, Zaifei; Zhang, Chi; Dong, Zixuan; Wang, Runqi; Chen, Qian; Liu, Xiangpeng; Jiang, Caifeng; Wang, Yalin; Guo, Bin; Zhou, Zhengyu; Jia, Zhihao; Sun, Hong; Feng, Yu","year":2026,"journal":"Cell & bioscience, 16(1), 18","doi":"10.1186/s13578-025-01525-4","pmid":"41526984","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide + Akk11 synergistically improved MASLD through reduced fat mass, better liver histology, decreased triglycerides, suppressed fatty acid synthesis, enhanced mitochondrial function, gut microbiota remodeling, and reduced intestinal/hepatic inflammation.","whyItMatters":"Fatty liver disease affects 30% of people globally with limited treatments. Combining GLP-1 drugs with targeted probiotics could provide the efficacy boost needed for more advanced disease.","specificNumbers":"","methodology":"Treatment of db/db mice with semaglutide alone or combined with Akk11, assessing metabolic parameters, liver/adipose histology, gut microbiota, transcriptomics, and inflammatory signaling.","limitations":"Mouse model (db/db). Human gut environment differs. Akk11 manufacturing and regulatory pathway unclear. Dose optimization for human use needed."},{"rthcId":"RPEP-15193","title":"Brain natriuretic peptide protects against acute pulmonary embolism-induced pulmonary vasoconstriction through natriuretic peptide receptor C.","authors":"Gao, Yizhuo; Liu, Shiqi; Gu, Zhichun; Wei, Xuejiao; Han, Xue; Wei, Shibo; Yang, Jing; Liu, Yuchen; Jia, Dong","year":2026,"journal":"Basic research in cardiology","doi":"10.1007/s00395-026-01166-9","pmid":"41781760","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BNP reduced right ventricular pressure and improved survival in PE rats, and improved clinical outcomes in intermediate-high-risk PE patients, through NPRC-mediated NADPH oxidase 2 reduction and decreased myosin light chain phosphorylation in PA smooth muscle.","whyItMatters":"PE is the third leading cause of cardiovascular death. BNP could provide a new treatment option for intermediate-high-risk patients who are too unstable for standard therapy alone.","specificNumbers":"","methodology":"Rat PE model with autologous thrombi, BNP dose optimization, mechanistic studies (oxidative stress, NPRC signaling), and observational comparison of PE patients receiving BNP + anticoagulation vs anticoagulation alone.","limitations":"Small clinical observation (not randomized). Rat PE model may not fully replicate human PE. BNP dosing optimization for PE needs further study. NPRC-mediated mechanism needs human validation."},{"rthcId":"RPEP-15194","title":"Toward development of a dynamic supramolecular peptide therapy for acute ischemic stroke.","authors":"Gao, Zijun; Andrade da Silva, Luisa Helena; Li, Zhiwei; Chen, Feng; Smith, Cara; Lipfert, Zoie; Martynowicz, Ryan; Arias, Erika; Muller, William A; Sullivan, David P; Stupp, Samuel I; Batra, Ayush","year":2026,"journal":"Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, e00820","doi":"10.1016/j.neurot.2025.e00820","pmid":"41506958","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Systemically delivered IKVAV-PA crossed the BBB, localized to the ischemic hemisphere (confirmed by intravital imaging), and significantly reduced infarct volume vs saline at 7 days post-stroke with good organ biocompatibility.","whyItMatters":"Stroke is a leading cause of disability. An injectable peptide therapy that protects the brain after reperfusion could save millions of neurons and improve functional outcomes.","specificNumbers":"","methodology":"Transient MCAO in CX3CR1-GFP mice, IV IKVAV-PA administration at reperfusion, intracranial intravital and wide-field imaging for PA distribution, cresyl violet staining for infarct volume at 7 days, and systemic organ histology.","limitations":"Mouse model. Single timepoint (7 days). Functional behavioral outcomes not assessed. PA pharmacokinetics not fully characterized."},{"rthcId":"RPEP-15195","title":"Antimicrobial peptides RI8 and RW8 target bacterial membranes and genomic DNA to overcome drug resistance.","authors":"Gao, Ziwei; Zhang, Meng-Yue; Cheng, Yan-Liang; Shi, Yi-Fan; Shan, Xiao-Le; Zhang, Zi-Xuan; Han, Yu-Ling; Li, Shuang","year":2026,"journal":"Bioorganic chemistry, 172, 109599","doi":"10.1016/j.bioorg.2026.109599","pmid":"41650916","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"RI8: MIC 2-16 μg/mL broad-spectrum, therapeutic index 39.4, <1% hemolysis. RW8: protease-resistant, 71.4% biofilm inhibition. Both: dual membrane/DNA mechanism, 2-5 log wound reduction, outperformed levofloxacin in pneumonia (3-5 vs 2 logs).","whyItMatters":"These peptides solve two major AMP problems: protease degradation and narrow spectrum. Their rational design creates a versatile platform for different infection types.","specificNumbers":"","methodology":"Rational peptide design with (RRYY)2P(YYRR)2 scaffold, MIC/hemolysis/serum stability assays, MD simulations, biofilm assays, murine MDR wound and S. aureus pneumonia models.","limitations":"Mouse models. Manufacturing costs of designed peptides. Long-term resistance development not tested beyond initial assays. Pharmacokinetics need full characterization."},{"rthcId":"RPEP-15196","title":"Real-world comparison of treatments with antibodies targeting the CGRP pathway or botulinum toxin type A for resistant migraine.","authors":"Gardon, L; Guy, D; Pereira, B; Sickout-Arondo, S; Mongaret, C; Delage, N; Picard, P; Condé, S; Moisset, X","year":2026,"journal":"Revue neurologique, 182(1-2), 59-64","doi":"10.1016/j.neurol.2025.10.006","pmid":"41387033","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"≥50% responder rate: anti-CGRP mAbs 43% vs BTX-A 18% (p=0.003). ≥30% responder rate: 54% vs 36% (p=0.06). Significantly greater MHD reduction with anti-CGRP mAbs at 3 months (p=0.015) and 6 months (p=0.022).","whyItMatters":"Treatment-resistant migraine patients need to know which option works better. This direct comparison provides evidence favoring anti-CGRP antibodies over Botox.","specificNumbers":"","methodology":"Single-center retrospective cohort with 93 resistant migraine patients (50 anti-CGRP, 43 BTX-A), propensity score matching and IPTW adjustment, 6-month follow-up.","limitations":"Single center. Retrospective. Relatively small sample. Cannot determine if results generalize to all anti-CGRP drugs equally."},{"rthcId":"RPEP-15197","title":"Advances in Peptide-Based Cancer Vaccines: Materials, Targeting, and Delivery Strategies.","authors":"Garland, Shea; Lux, Jacques","year":2026,"journal":"Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology, 18(1), e70044","doi":"10.1002/wnan.70044","pmid":"41467611","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Novel platforms for peptide cancer vaccines using advanced materials, adjuvants, targeting, and controlled release are overcoming barriers of immune tolerance, poor delivery, and immunosuppressive microenvironment.","whyItMatters":"Immune checkpoint drugs work for only a subset of patients. Peptide vaccines could prime the immune system to respond to these drugs, expanding their benefit to many more cancer patients.","specificNumbers":"","methodology":"Review of recent advances in peptide-based cancer vaccine design, covering materials, adjuvants, targeting strategies, controlled release, and clinical translation.","limitations":"Many platforms still in preclinical stages. Personalized neoantigen vaccines are expensive. Cold tumor conversion remains challenging."},{"rthcId":"RPEP-15198","title":"The Enterolimbic Axis: Gut-Brain Affective Circuits at the Crossroad of Metabolism, Emotion, and Behavior.","authors":"Gasbarrini, Antonio; Galli, Francesca Sofia; Ianiro, Gianluca; Ponziani, Francesca; Rinninella, Emanuele","year":2026,"journal":"The American journal of gastroenterology","doi":"10.14309/ajg.0000000000003907","pmid":"41504341","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The enterolimbic axis integrates gut-derived GLP-1, GIP, and SCFAs with hypothalamic and mesolimbic reward pathways, supporting the repositioning of incretin therapies for metabolic, eating, and affective disorders.","whyItMatters":"Understanding that gut peptides control both metabolism and mood/reward redefines how we think about obesity, eating disorders, and mental health — and who should prescribe treatments.","specificNumbers":"","methodology":"Conceptual review integrating molecular, clinical, and therapeutic evidence on the enterolimbic axis and its implications for precision medicine.","limitations":"Conceptual framework. Direct evidence for some proposed pathways is limited. Clinical applications are emerging but not fully validated."},{"rthcId":"RPEP-15199","title":"Lung SPLUNC1-derived anti-biofilm peptide in polymeric nanoparticles: A novel strategy against S. aureus biofilms and antimicrobial resistance.","authors":"Gaur, Manish; Maurya, Sarita; Tripathi, Ritu; Pasupuleti, Mukesh; Akhtar, Md Sohail; Swaroop, Shiv; Yadav, Awadh Bihari","year":2026,"journal":"International journal of biological macromolecules, 339(Pt 2), 149552","doi":"10.1016/j.ijbiomac.2025.149552","pmid":"41380897","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"KQ peptide in PLGA-chitosan NPs: 60.99% biofilm reduction, >92% cell viability in A549 cells, <1% hemolysis, 150-350 nm size, sustained release 72h, aerodynamic diameter ≤5 μm for deep lung delivery.","whyItMatters":"Chronic lung infections with biofilm-forming S. aureus are extremely difficult to treat. An inhaled peptide therapy that disrupts biofilms could transform management of conditions like cystic fibrosis lung infections.","specificNumbers":"","methodology":"Rational peptide design from SPLUNC1, PLGA and PLGA-chitosan nanoparticle formulation, characterization (size, zeta potential, SEM/TEM, encapsulation, release), anti-biofilm assays, cytotoxicity (A549), hemolysis, and NGI aerodynamic assessment.","limitations":"In vitro only. In vivo lung infection models needed. Manufacturing scalability of peptide-loaded nanocomposites uncertain."},{"rthcId":"RPEP-15200","title":"CGRP/TSP1 Signaling Dampens Corneal Inflammation and Fibrosis by Targeting A2M During Corneal Stromal Wound Healing.","authors":"Ge, Hongqi; Zhang, Yangyang; Guo, Qian; Li, Ya; Yang, Lingling; Zang, Xinyi; Xie, Jin; Wang, Yao; Li, Yizhou; Qi, Xia; Wang, Yalin; Zhou, Qingjun; Wang, Xiaolei","year":2026,"journal":"Investigative ophthalmology & visual science, 67(1), 10","doi":"10.1167/iovs.67.1.10","pmid":"41533912","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CGRP induces TSP1 and A2M expression (both in vitro and in vivo). CGRP receptor antagonism (BIBN4096) suppresses TSP1/A2M and worsens corneal lesions. Thbs1-/- mice show exacerbated corneal inflammation and fibrosis. Pathway conserved in human corneal injury.","whyItMatters":"Anti-CGRP migraine drugs are used by millions. This study shows CGRP protects the cornea from injury — raising important safety questions about long-term corneal health in migraine patients on CGRP-blocking drugs.","specificNumbers":"","methodology":"Corneal stromal injury model in WT and Thbs1-/- mice, single-cell/bulk RNA sequencing, human keratocyte studies, CGRP receptor antagonism (BIBN4096), A2M depletion, and human corneal scar tissue analysis.","limitations":"Mouse models may not fully replicate human corneal biology. BIBN4096 is short-acting. Long-term effects of chronic CGRP blockade on corneal health unknown. Human tissue analysis was observational."},{"rthcId":"RPEP-15201","title":"Clinical review of how glucagon-like peptide-1 agonist obesity medications decrease sexual desire, and a biopsychosocial model for why we don't 'see' it.","authors":"Gelfand, Sonya T; Tveit, Meghan C; Simon, James A","year":2026,"journal":"Obesity pillars, 17, 100233","doi":"10.1016/j.obpill.2025.100233","pmid":"41404471","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 agonism may decrease sexual desire via 5-HT2C serotonergic activation (analogous to SSRIs), but competing positive factors (testosterone increase, improved vasculature, mood) likely offset this effect in many patients.","whyItMatters":"Sexual desire is crucial to quality of life. Understanding that GLP-1 drugs have competing positive and negative effects on sexual function helps clinicians counsel patients appropriately.","specificNumbers":"","methodology":"Narrative review with targeted PubMed literature search, integrating evidence on GLP-1/serotonin interactions, sexual function, and a biopsychosocial framework analysis.","limitations":"Entirely theoretical model. No direct measurement of 5-HT2C activation by GLP-1 drugs in humans. Biopsychosocial framework is speculative. No clinical trials measuring sexual desire as primary outcome."},{"rthcId":"RPEP-15202","title":"GLP-1 receptor agonists and obstructive lung disease: Beyond metabolic control to respiratory outcomes.","authors":"Georgakopoulou, Vasiliki Epameinondas; Dalamaga, Maria","year":2026,"journal":"Metabolism open, 29, 100449","doi":"10.1016/j.metop.2026.100449","pmid":"41717504","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Real-world evidence consistently links GLP-1 RA use to reduced COPD/asthma exacerbations, most pronounced in obese frequent exacerbators. Emerging disease-focused RCTs confirm respiratory benefits. Mechanisms include metabolic improvement and direct GLP-1R-mediated airway/immune modulation.","whyItMatters":"COPD is the third leading cause of death globally. If GLP-1 drugs can reduce exacerbations—the main driver of COPD mortality and cost—they could become part of standard lung disease management.","specificNumbers":"","methodology":"Comprehensive review of population cohort studies, comparative effectiveness analyses, meta-analyses, cardiovascular outcome trials, and emerging disease-focused RCTs on GLP-1 RAs and obstructive lung disease.","limitations":"Most evidence observational with residual confounding. CV outcome trials were not designed for respiratory endpoints. Direct airway effects need more human validation."},{"rthcId":"RPEP-15203","title":"Metformin provides superior neuroprotective potential compared to semaglutide in preventing diabetes-associated Alzheimer's disease via dual actions.","authors":"Georgiou, Andrea; Zanos, Panos; Onisiforou, Anna","year":2026,"journal":"Communications medicine","doi":"10.1038/s43856-026-01471-3","pmid":"41760788","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Metformin ranked highest for AD protection via AMPK/insulin/adipocytokine pathways. Semaglutide ranked among the least effective, showing minimal engagement with DM2-AD comorbidity network pathways. Insulin/GLP-1 combinations showed effects comparable to metformin.","whyItMatters":"Despite enormous excitement about semaglutide for AD, this computational analysis suggests metformin may actually be the better diabetes drug for brain protection, redirecting research priorities.","specificNumbers":"","methodology":"Integrative comparative network pharmacology of 39 diabetes therapies within the DM2-AD pathway-pathway comorbidity network, validated with gene expression data.","limitations":"Computational analysis only. Network pharmacology predicts pathway engagement, not clinical outcomes. Rodent gene expression validation may not translate to humans. Does not account for drug concentrations in the brain."},{"rthcId":"RPEP-15204","title":"First successful protocol for desensitization to eptinezumab.","authors":"Gerard, Benoit; Praudel, Hubert; Lanteri-Minet, Michel; Van Obberghen, Elise; Rocher-Moreau, Fanny; Rousset, Johanna; Jacquier, Ulysse; Leroy, Sylvie; Delin, Margot","year":2026,"journal":"Headache, 66(2), 556-559","doi":"10.1111/head.70000","pmid":"41420316","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Two patients with eptinezumab hypersensitivity reactions had negative skin tests (non-IgE mechanism) and successfully completed a 10-step hospital-based desensitization protocol, enabling safe drug readministration.","whyItMatters":"For patients who react to anti-CGRP drugs but need them for migraine, desensitization could be the only way to continue this effective treatment class.","specificNumbers":"","methodology":"Two case reports with skin testing (prick and intradermal) followed by a 10-step graded-dose desensitization protocol for eptinezumab IV administration.","limitations":"Only two patients. Non-IgE mechanism means desensitization may not work for true allergic reactions. Hospital-based protocol requires significant resources."},{"rthcId":"RPEP-15205","title":"Global glucagon-like peptide-2 receptor activation linked to increased obesity risk in the UK Biobank.","authors":"Gerlach, Peter A; Gadgaard, Sarina; Madsen, Jakob S; Lindquist, Peter; Lorente, Javier Sanchez; Faas, Felix; Gabe, Maria B N; Rosenkilde, Mette M; Hauser, Alexander S","year":2026,"journal":"Metabolism: clinical and experimental, 177, 156489","doi":"10.1016/j.metabol.2025.156489","pmid":"41519224","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"D470N (32% frequency) increases GLP-2R cAMP via reduced β-arrestin/internalization and is associated with increased obesity, T2D, BMI, body fat, HbA1c, and blood pressure in ~500K UK Biobank participants. LoF variants associated with decreased obesity/fat.","whyItMatters":"GLP-2R drugs are being developed for intestinal diseases. This study reveals unexpected metabolic risks of GLP-2R activation that must be monitored in drug development.","specificNumbers":"","methodology":"In vitro pharmacological characterization of 30 GLP-2R missense variants (cAMP, β-arrestin 2), identification of 34 predicted LoF variants, and genetic association testing in ~500,000 UK Biobank participants.","limitations":"Genetic associations don't prove causation. Tissue-specific GLP-2R effects may differ (gut beneficial, systemic harmful). UK Biobank population may not represent all ethnicities."},{"rthcId":"RPEP-15206","title":"Investigating the role of melanocortinergic, glutamatergic and neuropeptide Y systems on hypophagia caused by gastric inhibitory polypeptide (GIP) in broilers.","authors":"Gharaie, Maryam Lotfi; Zendehdel, Morteza; Zarei, Hamed; Mahdavi, Kimia","year":2026,"journal":"Poultry science, 105(2), 106324","doi":"10.1016/j.psj.2025.106324","pmid":"41468751","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Melanocortin (α-MSH/AgRP), glutamatergic, and NPY systems form an interconnected appetite control network with extensive cross-talk, supporting multi-target therapeutic approaches for obesity.","whyItMatters":"Understanding how appetite-regulating peptide systems interact is essential for designing next-generation obesity drugs that target multiple pathways simultaneously.","specificNumbers":"","methodology":"Narrative review of the interplay between melanocortinergic, glutamatergic, and neuropeptide Y systems in appetite regulation and energy homeostasis.","limitations":"Review of primarily preclinical evidence. Human brain peptide circuit dynamics are difficult to measure directly. Translation to therapeutics is complex."},{"rthcId":"RPEP-15207","title":"Arthropod venom peptides: Pioneering nanotechnology in cancer treatment and drug delivery.","authors":"Ghodeif, Sara K; El-Fahla, Nadia A; Abdel-Rahman, Mohamed A; El-Shenawy, Nahla S","year":2026,"journal":"Cancer pathogenesis and therapy, 4(2), 81-97","doi":"10.1016/j.cpt.2025.03.005","pmid":"41541913","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Arthropod venom peptides exhibit multi-mechanism anticancer activity (membrane disruption, apoptosis, anti-angiogenesis, immune modulation), with nanodelivery systems overcoming stability, toxicity, and targeting limitations.","whyItMatters":"Cancer treatment needs new approaches. Venom peptides offer multi-mechanism killing that could overcome drug resistance, and nanotechnology makes them clinically practical.","specificNumbers":"","methodology":"Comprehensive review of arthropod venom peptide anticancer mechanisms and nanotechnology-based delivery platforms, covering literature from 2000-2025.","limitations":"Most evidence preclinical. Venom peptide toxicity management remains challenging. Manufacturing at scale is complex."},{"rthcId":"RPEP-15208","title":"Reining in Multidrug Resistance Protein 1 via Binding Its Flexible Interdomain Linker with Sequence-Selective Peptide-Binding Nanoparticles.","authors":"Ghosh, Avijit; Sharma, Mansi; Zhao, Yan","year":2026,"journal":"Biomacromolecules","doi":"10.1021/acs.biomac.5c02567","pmid":"41700341","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A peptide targeting MRP1's flexible interdomain linker inhibited drug efflux and reversed multidrug resistance by a novel mechanism distinct from substrate-based approaches.","whyItMatters":"Multidrug resistance causes most cancer treatment failures. Targeting transporter flexibility with peptides offers a fundamentally new approach.","specificNumbers":"","methodology":"Computational analysis of MRP1 interdomain linker dynamics, peptide design, molecular docking and dynamics simulations, and drug efflux functional assays.","limitations":"In vitro evidence. Peptide stability and delivery in vivo not addressed. MRP1 is expressed in normal tissues, so selectivity needs optimization."},{"rthcId":"RPEP-15209","title":"Mapping the structural and dynamic behavior of an antimicrobial peptide transporter from non-typeable Haemophilus influenzae.","authors":"Ghosh, Kalyan; Baid, Harsh Vardhan; Dasgupta, Pratik; Kanaujia, Shankar Prasad","year":2026,"journal":"International journal of biological macromolecules, 338(Pt 1), 149605","doi":"10.1016/j.ijbiomac.2025.149605","pmid":"41390022","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Structural and dynamic mapping of the Sap AMP transporter revealed peptide import mechanisms, informing strategies to exploit bacterial AMP uptake pathways.","whyItMatters":"Understanding how bacteria handle AMPs is crucial for designing peptides that bacteria cannot neutralize through uptake and degradation.","specificNumbers":"","methodology":"Structural biology and molecular dynamics characterization of the Sap ABC transporter from non-typeable H. influenzae.","limitations":"Structural characterization only. Functional validation of import mechanisms incomplete. Applicability to other pathogens's transporters needs investigation."},{"rthcId":"RPEP-15210","title":"AMP-CapsNet: a multi-view feature fusion approach for antimicrobial peptide prediction using capsule networks.","authors":"Ghulam, Ali; Rehman, Mujeebu; Fida, Huma; Zhao, Pei-Yu; Noroze, Ramsha; Qi, Ye-Chen; Yu, Xiao-Long","year":2026,"journal":"Genomics & informatics","doi":"10.1186/s44342-026-00067-6","pmid":"41654884","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"AMP-CapsNet combines multi-view feature fusion with capsule neural networks for AMP prediction, achieving improved accuracy over existing computational methods through integrated sequence and physicochemical analysis.","whyItMatters":"Faster, more accurate AMP prediction accelerates discovery of new antibiotics from the millions of potential peptide sequences.","specificNumbers":"","methodology":"Development and validation of capsule neural network with multi-view feature inputs (amino acid composition, physicochemical properties, evolutionary features) for binary AMP/non-AMP classification.","limitations":"Computational prediction only. Predictions need experimental validation. May not capture activity against specific pathogen types."},{"rthcId":"RPEP-15211","title":"Predicting Pharmacological Treatment Response in Migraine Using AI/ML: A Scoping Review of the Evidence and Future Directions.","authors":"Giacon, Martina; Terrazzino, Salvatore","year":2026,"journal":"Pharmacotherapy, 46(2), e70085","doi":"10.1002/phar.70085","pmid":"41276479","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"AI/ML models can predict migraine treatment response with varying accuracy, potentially enabling precision prescribing for anti-CGRP therapies and other migraine drugs, though validation and standardization are needed.","whyItMatters":"Moving from trial-and-error to precision migraine prescribing could reduce patient suffering and healthcare costs by getting the right treatment right the first time.","specificNumbers":"","methodology":"Scoping review of AI/ML studies predicting pharmacological treatment response in migraine, covering clinical, imaging, genetic, and biomarker prediction features.","limitations":"Most studies have small datasets. External validation rare. No standardized treatment response definitions. Heterogeneous AI/ML methods."},{"rthcId":"RPEP-15212","title":"Design of co-lyophilised ternary insulin-sucrose-polymer systems with enhanced amorphous glass stability.","authors":"Giannachi, Claudia; Allen, Evin; Vucen, Sonja; Crean, Abina","year":2026,"journal":"European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 218, 107450","doi":"10.1016/j.ejps.2026.107450","pmid":"41580054","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Ternary insulin-sucrose-polymer lyophilized systems maintained amorphous glass stability and protected insulin bioactivity through manufacturing compression, temperature stress, storage humidity, and simulated GI conditions.","whyItMatters":"Oral insulin has been pursued for decades without success. Solving the stability problem during manufacturing and storage is a crucial step toward making it reality.","specificNumbers":"","methodology":"Co-lyophilization of insulin with sucrose and various polymers, characterization by DSC, FTIR, and stability testing under manufacturing (compression), storage (ICH conditions), and simulated GI challenges.","limitations":"In vitro stability testing. Oral bioavailability in vivo not assessed. Specific polymer combinations need optimization for each peptide drug. Manufacturing scale-up needed."},{"rthcId":"RPEP-15213","title":"Monogenic obesity due to MC4R deficiency: lessons from a multigenerational case.","authors":"Giannopoulou, Eleni Z; Zorn, Stefanie; Schirmer, Melanie; Brandt-Heunemann, Stephanie; Schnurbein, Julia von; Nestoris, Claudia; Moawia, Abubakar; Siebert, Reiner; Denzer, Christian; Wabitsch, Martin","year":2026,"journal":"Molecular and cellular pediatrics, 13(1), 3","doi":"10.1186/s40348-025-00214-z","pmid":"41489710","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"MC4R deficiency caused multigenerational severe obesity diagnosed only after decades of failed treatments, highlighting the need for early genetic testing and availability of targeted melanocortin therapies.","whyItMatters":"About 5% of severely obese individuals may have MC4R mutations. Diagnosing them enables targeted treatment with melanocortin pathway drugs instead of futile dietary interventions.","specificNumbers":"","methodology":"Detailed multigenerational case report with genetic testing, clinical history, treatment outcomes, and therapeutic implications.","limitations":"Single family case report. Genetic testing availability and cost vary globally. Not all MC4R variants respond equally to melanocortin agonists."},{"rthcId":"RPEP-15214","title":"Deinsulinisation in type 2 Diabetes: Evidence-based strategies for safe treatment simplification \"Approaches to reducing insulin in type 2 diabetes\".","authors":"Giorda, Carlo B; Anelli, Valentina; Goglia, Umberto; Riu, Stefano De; Russo, Giuseppina; Gallo, Marco; Cosmo, Salvatore De; Corigliano, Gerardo; Modestino, Michele Roberto","year":2026,"journal":"Diabetes research and clinical practice, 231, 113056","doi":"10.1016/j.diabres.2025.113056","pmid":"41390000","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RAs enable safe insulin dose reduction or complete deinsulinization in advanced T2D, with maintained glycemic control, reduced hypoglycemia, and weight loss.","whyItMatters":"Millions of T2D patients are on insulin they may no longer need. Safe deinsulinization with GLP-1 drugs can eliminate the burden and risks of unnecessary insulin therapy.","specificNumbers":"","methodology":"Evidence-based review of strategies for insulin reduction and discontinuation using GLP-1 RAs and SGLT2i in advanced T2D.","limitations":"Not all patients can discontinue insulin. Careful monitoring required during tapering. Some patients need insulin for beta-cell failure regardless of GLP-1 therapy."},{"rthcId":"RPEP-15215","title":"GLP-1 receptor agonists and coronary plaques regression in diabetic patients after acute coronary syndromes.","authors":"Gitto, Mauro; Catapano, Federica; Francone, Marco; Mincione, Gianluca; Scialò, Vincenzo; Pivato, Carlo A; Lisi, Costanza; Regazzoli, Damiano; Cao, Davide; Fiorina, Roberta Maria; Petrelli, Alessandra; Bucciarelli, Loredana; Loretelli, Cristian; Condorelli, Gianluigi; Fiorina, Paolo; Stefanini, Giulio","year":2026,"journal":"Acta diabetologica, 63(2), 179-191","doi":"10.1007/s00592-025-02606-z","pmid":"41186740","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RAs were associated with coronary plaque regression after ACS in diabetic patients, through anti-inflammatory, endothelial, and metabolic mechanisms complementary to statin-mediated lipid lowering.","whyItMatters":"Coronary plaque regression is the holy grail of cardiology — actually reversing heart disease rather than just slowing it. GLP-1 drugs may provide this benefit.","specificNumbers":"","methodology":"Review of clinical evidence on GLP-1 RA effects on coronary atherosclerosis progression and regression in diabetic ACS patients.","limitations":"Evidence mostly from observational imaging studies. Randomized trials with intravascular imaging endpoints needed. Cannot separate weight loss effects from direct vascular effects."},{"rthcId":"RPEP-15216","title":"GLP1-1RAs improve walking distance and reduce amputation in people with type 2 diabetes and peripheral artery disease: A systematic review and meta-analysis of randomised controlled trials and cohort studies.","authors":"Giugliano, Dario; Longo, Miriam; Di Martino, Nicole; Scappaticcio, Lorenzo; Caruso, Paola; Bellastella, Giuseppe; Maiorino, Maria Ida; Esposito, Katherine","year":2026,"journal":"Diabetes, obesity & metabolism","doi":"10.1111/dom.70454","pmid":"41508745","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RAs associated with improved functional walking distance, reduced MALE, and lower amputation rates in T2D patients with PAD.","whyItMatters":"PAD-related amputations are devastating and often preventable. GLP-1 drugs improving walking distance means better quality of life and potentially fewer amputations.","specificNumbers":"","methodology":"Systematic review and meta-analysis evaluating GLP-1 RA effects on walking distance, MALE, and amputations in T2D patients with PAD.","limitations":"Most evidence observational. Heterogeneity across studies. Cannot determine optimal GLP-1 drug or dose for PAD."},{"rthcId":"RPEP-15217","title":"Non-neuronal targets for migraine therapy.","authors":"Gliga, Otilia; Feliu-Soler, Albert; Vila-Pueyo, Marta","year":2026,"journal":"Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, e00845","doi":"10.1016/j.neurot.2026.e00845","pmid":"41644321","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Non-neuronal targets in migraine include meningeal immune cells, vascular smooth muscle, and endothelial cells, all modulated by CGRP and other neuropeptides, offering additional therapeutic opportunities beyond neuronal targeting.","whyItMatters":"Understanding migraine as more than a nerve disease reveals why some patients don't respond to current treatments and identifies new drug targets.","specificNumbers":"","methodology":"Narrative review of non-neuronal cellular targets in migraine pathophysiology, focusing on immune, vascular, and endothelial mechanisms and their interactions with neuropeptides.","limitations":"Many non-neuronal mechanisms are from animal models. Human validation of specific cellular targets needed. New therapeutic approaches are mostly conceptual."},{"rthcId":"RPEP-15218","title":"Targeted paclitaxel delivery in ovarian cancer via AP1-functionalized elastin-like polypeptide nanocarriers: development and characterization.","authors":"Goel, Ridhima; Alvi, Shakeel; Ali, Rashid; Sharma, Pradeep; Bhattacharyya, Jayanta; Sarangthem, Vijaya; Singh, Thoudam Debraj","year":2026,"journal":"BMC cancer, 26(1)","doi":"10.1186/s12885-026-15615-0","pmid":"41588372","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"AP1-functionalized ELP nanoparticles selectively delivered paclitaxel to ovarian cancer via IL-4R targeting with improved tumor accumulation and reduced off-target toxicity.","whyItMatters":"Ovarian cancer is often diagnosed late with limited treatment options. Peptide-targeted delivery could make existing chemotherapy drugs more effective and less toxic.","specificNumbers":"","methodology":"Design and characterization of AP1-ELP nanoparticles loaded with paclitaxel, cellular uptake studies, IL-4R targeting validation, and in vivo ovarian cancer model evaluation.","limitations":"Preclinical study. IL-4R expression varies across ovarian cancer subtypes. Manufacturing scale-up of recombinant ELPs not fully addressed."},{"rthcId":"RPEP-15219","title":"GLP-1RA Liraglutide Attenuates Sepsis by Modulating Gut Microbiota and Associated Metabolites.","authors":"Gong, Bing; Shi, Zhuang'e; Qi, Jialong; Wang, Fuping; Chen, Guobing; Su, Heng","year":2026,"journal":"Nutrients, 18(3)","doi":"10.3390/nu18030531","pmid":"41683353","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Liraglutide modulated gut microbiota composition in septic mice, altering associated metabolic pathways and reducing sepsis-induced organ dysfunction and inflammation.","whyItMatters":"Sepsis kills 11 million people annually worldwide. A widely available drug that protects through the gut-organ axis could save lives.","specificNumbers":"","methodology":"Sepsis model in mice with liraglutide treatment, gut microbiota 16S rRNA sequencing, metabolomic analysis, organ dysfunction assessment, and inflammatory marker profiling.","limitations":"Mouse model. Human sepsis is heterogeneous. Cannot determine if microbiota changes are cause or effect of protection. Dosing optimization needed."},{"rthcId":"RPEP-15220","title":"Glucagon-like Peptide-1 Receptor Agonists and Ocular Disease: Mechanisms, Evidence and Therapeutic Perspectives.","authors":"Gong, Xiaoming; Örge, Faruk H","year":2026,"journal":"International journal of molecular sciences, 27(3)","doi":"10.3390/ijms27031432","pmid":"41683853","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RAs show potential retinal benefits (DR, AMD) through anti-inflammatory/neuroprotective mechanisms, but effects on glaucoma (IOP) and NAION risk require monitoring, creating a nuanced ocular safety-benefit profile.","whyItMatters":"Millions of GLP-1 drug users are at risk for diabetic eye disease. Understanding both benefits and risks guides ophthalmologic management.","specificNumbers":"","methodology":"Review of preclinical and clinical evidence on GLP-1 RA effects across glaucoma, diabetic retinopathy, age-related macular degeneration, and NAION.","limitations":"Most ocular evidence is preclinical or observational. No dedicated ophthalmologic RCTs for GLP-1 drugs. NAION association remains uncertain."},{"rthcId":"RPEP-15221","title":"Optimized Zebrafish AP2M1A-Derived Decapeptide AP10RW with Robust Stability Suppresses Multidrug-Resistant Bacteria.","authors":"Gong, Yi; Li, Jun; Zhang, Yameng; Zhang, Xiaozheng; Xie, Jun","year":2026,"journal":"Biomolecules, 16(2)","doi":"10.3390/biom16020207","pmid":"41750278","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"AP10RW, an optimized decapeptide from zebrafish AP2M1A, demonstrated robust antimicrobial activity with enhanced stability through targeted amino acid modifications.","whyItMatters":"Zebrafish are a model organism whose immune peptides are increasingly recognized as drug leads. Optimization demonstrates these peptides can be engineered for therapeutic use.","specificNumbers":"","methodology":"Rational peptide optimization from zebrafish AP2M1A, stability testing, antimicrobial activity assays.","limitations":"In vitro characterization. In vivo efficacy and toxicity not assessed. Limited to antibacterial testing."},{"rthcId":"RPEP-15222","title":"GLP-1 receptor agonists reduce body mass index and total daily insulin dose in youth with type 1 diabetes: a retrospective cohort study.","authors":"Gonzalez, Frances; Reid, Mark W; Garcia, Jaquelin Flores; Raymond, Jennifer K; Chao, Lily C","year":2026,"journal":"Journal of pediatric endocrinology & metabolism : JPEM, 39(2), 166-172","doi":"10.1515/jpem-2025-0568","pmid":"41353583","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RAs reduced BMI and total daily insulin dose in youth with T1D and obesity while maintaining glycemic control.","whyItMatters":"Youth T1D + obesity is a growing problem with no good treatment options. GLP-1 drugs could address both by reducing insulin requirements and promoting weight loss.","specificNumbers":"","methodology":"Study evaluating GLP-1 RA effects on BMI, insulin dose, and glycemic control in youth with T1D and obesity.","limitations":"Specific study details limited in abstract. Youth T1D populations are heterogeneous. Long-term effects unknown."},{"rthcId":"RPEP-15223","title":"Antiobesogenic effect of hydrolysates and peptide fractions of porcine collagen after in vitro gastrointestinal digestion.","authors":"González-Noriega, Julio A; Valenzuela-Melendres, Martín; Hernández-Mendoza, Adrián; Astiazarán-García, Humberto; Islava-Lagarda, Thalia; Tortoledo-Ortiz, Orlando; de la Garza, Ana Laura; Gutierrez-Pacheco, Samaria L; Alvarez-Armenta, Andrés; Ríos-Castro, Emmanuel; Huerta-Ocampo, José A; Peña-Ramos, E Aída","year":2026,"journal":"Journal of proteomics, 322, 105539","doi":"10.1016/j.jprot.2025.105539","pmid":"41067687","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"PSCH maintained ACE inhibitory activity after simulated GI digestion, with specific peptide fractions showing both ACEi and antiobesogenic effects, demonstrating bioactive peptide survival through digestion.","whyItMatters":"Validating that food-derived peptides survive digestion and remain active is crucial for developing functional foods and nutraceuticals.","specificNumbers":"","methodology":"Porcine skin collagen hydrolysis, peptide fraction separation, ACE inhibition assays before and after simulated GI digestion, and antiobesogenic activity evaluation.","limitations":"In vitro digestion simulation. In vivo blood pressure and anti-obesity effects need confirmation. Specific active peptides not fully identified."},{"rthcId":"RPEP-15224","title":"An experimental medicine protocol for exploring the haemodynamic effects of dual agonism at the glucagon-like peptide-1 and glucagon receptor in healthy subjects.","authors":"Goodman, James; Parker, Victoria E; McEniery, Carmel M; Di Stefano, Giovanni; Hubsch, Annette; Vamvaka, Evangelia; Helmy, Jo; Kaloyirou, Fotini; Jalaludeen, Navazh; Barker, Peter; Jermutus, Lutz; Cheriyan, Joseph; Ambery, Philip; Wilkinson, Ian B","year":2026,"journal":"British journal of clinical pharmacology, 92(2), 579-588","doi":"10.1002/bcp.70282","pmid":"41025322","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"An experimental medicine protocol for systematically evaluating acute hemodynamic effects of GLP-1/glucagon dual agonists, addressing cardiovascular safety concerns about glucagon receptor agonism.","whyItMatters":"Glucagon increases heart rate and energy expenditure, but the cardiovascular safety of chronic glucagon receptor activation is unknown. This protocol addresses a critical knowledge gap.","specificNumbers":"","methodology":"Experimental medicine study protocol for healthy volunteers, measuring acute cardiovascular parameters (HR, BP, cardiac output, SVR) after GLP-1/glucagon dual agonist administration.","limitations":"Protocol description; no results yet. Acute effects may not predict chronic cardiovascular outcomes. Healthy volunteers may respond differently than obese/diabetic patients."},{"rthcId":"RPEP-15225","title":"Computational structure-based evaluation of antimicrobial peptides against OXA-51 β-lactamase in carbapenem-resistant Acinetobacter baumannii.","authors":"Gopikrishnan, Mohanraj; Doss C, George Priya","year":2026,"journal":"Advances in protein chemistry and structural biology, 149, 61-92","doi":"10.1016/bs.apcsb.2025.09.003","pmid":"41581941","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Computational analysis identified AMPs with strong binding to OXA-5 beta-lactamase, suggesting a dual-mechanism approach: direct bacterial killing plus resistance enzyme inhibition.","whyItMatters":"Combining membrane-disrupting AMPs with beta-lactamase inhibition could restore antibiotic effectiveness against resistant bacteria.","specificNumbers":"","methodology":"Structure-based computational evaluation using molecular docking and molecular dynamics simulations of AMP-OXA-5 interactions.","limitations":"Entirely computational. Binding predictions need experimental validation. OXA-5 is one of many resistance enzymes."},{"rthcId":"RPEP-15226","title":"Peptide Arrays as Tools for Unraveling Tumor Microenvironments and Drug Discovery in Oncology.","authors":"Grab, Anna; Reißfelder, Christoph; Nesterov-Mueller, Alexander","year":2026,"journal":"Cells, 15(2)","doi":"10.3390/cells15020146","pmid":"41597221","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Peptide arrays provide high-throughput platforms for mapping tumor microenvironment interactions, biomarker discovery, and cancer drug candidate identification through systematic peptide-protein interaction analysis.","whyItMatters":"Understanding the tumor microenvironment at the peptide level is essential for developing targeted cancer therapies and diagnostic tools.","specificNumbers":"","methodology":"Review of peptide array technology applications in oncology, covering tumor microenvironment studies, biomarker discovery, and drug development.","limitations":"Array results need validation in biological systems. Surface-based interactions may not perfectly replicate in vivo conditions. Cost and complexity limit accessibility."},{"rthcId":"RPEP-15227","title":"Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs) for Obesity and Symptoms in Menopause: A Review.","authors":"Graczyk, Nicole A; Bisschops, Julia","year":2026,"journal":"Cureus, 18(1), e101693","doi":"10.7759/cureus.101693","pmid":"41704988","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RA effects in menopausal/postmenopausal women may differ from other populations due to hormonal changes affecting body composition and metabolism, with limited direct evidence available.","whyItMatters":"Menopausal women are a large GLP-1 drug user group but are understudied. Understanding sex- and hormone-specific effects is crucial for personalized prescribing.","specificNumbers":"","methodology":"Review of evidence on GLP-1 RA effects specifically in menopausal and postmenopausal women.","limitations":"Limited direct evidence. Most GLP-1 trials don't stratify by menopausal status. Extrapolation from general populations may be inaccurate."},{"rthcId":"RPEP-15228","title":"Nutritional Interventions in Type 1 Diabetes: Boosting Residual GLP-1 Responses-Is It an Option?","authors":"Grammatiki, Maria; Tsekmekidou, Xanthippi; Koufakis, Theocharis; Kotsa, Kalliopi","year":2026,"journal":"Nutrients, 18(4)","doi":"10.3390/nu18040564","pmid":"41754081","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Nutritional strategies (protein preloading, fiber supplementation, meal composition optimization) may enhance residual GLP-1 responses in T1D to preserve remaining beta-cell function and reduce insulin needs.","whyItMatters":"Preserving even a small amount of insulin production in T1D dramatically improves blood sugar control and reduces complications. Dietary GLP-1 boosting is accessible and affordable.","specificNumbers":"","methodology":"Review of evidence on dietary interventions to stimulate endogenous GLP-1 secretion in type 1 diabetes.","limitations":"Most evidence extrapolated from T2D and healthy populations. T1D-specific GLP-1 responses may differ. Dietary compliance is challenging."},{"rthcId":"RPEP-15229","title":"Evaluating dual calcitonin gene-related peptide antagonists for chronic migraine prevention.","authors":"Graves, Kara S; To, Jason; Paige, Hayley; Kennedy, Amanda G; Sprouse-Blum, Adam S; Devine, Derek; MacDougall, Julie","year":2026,"journal":"Headache","doi":"10.1111/head.70057","pmid":"41681042","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Dual CGRP pathway antagonism shows potential for chronic migraine through complementary mechanisms, with emerging evidence supporting combination anti-CGRP antibody + gepant approaches in partial responders.","whyItMatters":"Up to 50% of chronic migraine patients don't adequately respond to single anti-CGRP therapy. Dual targeting could help these patients.","specificNumbers":"","methodology":"Review evaluating the rationale, evidence, and safety considerations for dual CGRP antagonism in chronic migraine treatment.","limitations":"Limited clinical evidence for dual approaches. Safety of combining CGRP blockers unknown. Cost implications significant."},{"rthcId":"RPEP-15230","title":"The Antimicrobial Peptide C14R Is Active Against All Pathogenic Species of the ESKAPE Group.","authors":"Gruber, Daniel; Vogel, Verena; Walter, Jan-Christoph; Bolotnikov, Grigory; Rodríguez, Armando; Preising, Nico; Ständker, Ludger; Firacative, Carolina; Spellerberg, Barbara; Kissmann, Ann-Kathrin; Rosenau, Frank","year":2026,"journal":"Antibiotics (Basel, Switzerland), 15(2)","doi":"10.3390/antibiotics15020211","pmid":"41750508","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Synthetic AMP C14R demonstrated broad-spectrum pore-forming antibacterial activity against all pathogenic species of the ESKAPE group.","whyItMatters":"ESKAPE pathogens cause the majority of hospital-acquired infections and resist most antibiotics. A single peptide effective against all six is rare and valuable.","specificNumbers":"","methodology":"Antimicrobial activity testing of C14R against all ESKAPE pathogen species with mechanism of action characterization.","limitations":"Specific MIC values and in vivo data from abstract limited. Serum stability and toxicity need characterization."},{"rthcId":"RPEP-15231","title":"Myopia pathogenesis and vasoactive intestinal peptide: Molecular mechanisms, experimental models, and clinical implications.","authors":"Grubsic, Camila; Céspedes, Ricardo; Tapia, Felipe; Schmachtenberg, Oliver","year":2026,"journal":"Experimental eye research, 263, 110810","doi":"10.1016/j.exer.2025.110810","pmid":"41421442","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"VIP is involved in myopia pathogenesis through ocular growth signaling pathways, with potential as a biomarker and therapeutic target for myopia control.","whyItMatters":"Myopia is becoming epidemic and can lead to blindness. Understanding VIP's role could lead to peptide-based treatments that slow myopic progression.","specificNumbers":"","methodology":"Review of molecular mechanisms, expression studies, and experimental evidence linking VIP to myopia/ocular growth regulation.","limitations":"Mostly preclinical and molecular evidence. Human clinical validation of VIP as myopia biomarker needed. Therapeutic targeting not yet tested."},{"rthcId":"RPEP-15232","title":"Influence of N- and O-glycosylation on structural properties and biological activity of a C-terminal LL-37 fragment.","authors":"Grzywacz, Daria; Nuti, Francesca; Żamojć, Krzysztof; Samsonov, Sergey A; Malinowska, Marcelina; Paduszyńska, Małgorzata; Papini, Anna Maria; Makowska, Joanna","year":2026,"journal":"Carbohydrate research, 563, 109872","doi":"10.1016/j.carres.2026.109872","pmid":"41780202","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"N- and O-glycosylation differentially affected AMP structural properties, stability, and biological activity, providing systematic design rules for glycoengineered antimicrobial peptide therapeutics.","whyItMatters":"AMPs are promising antibiotics but unstable in the body. Glycosylation can fix this, and knowing which type to use is crucial for drug development.","specificNumbers":"","methodology":"Synthesis and characterization of O- and N-glycosylated AMP variants with structural (CD, NMR), stability (protease resistance), and functional (antimicrobial activity) analysis.","limitations":"Limited to specific AMP sequences. Effects may vary for different peptide scaffolds. In vivo validation needed."},{"rthcId":"RPEP-15233","title":"Adverse Events Associated with Tirzepatide: Updated Pharmacovigilance Analysis Using FAERS (2022 Q1-2025 Q1) with an Adapted Time-to-Onset Method.","authors":"Gu, Saisai","year":2026,"journal":"Drug, healthcare and patient safety, 18, 1-13","doi":"10.2147/DHPS.S556918","pmid":"41531800","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Updated FAERS analysis identifies emerging adverse event signals for tirzepatide across GI, hepatobiliary, and other organ systems, characterizing its real-world safety profile.","whyItMatters":"Tirzepatide is one of the fastest-growing drugs ever. Early detection of safety signals protects millions of new users.","specificNumbers":"","methodology":"Pharmacovigilance analysis of updated FAERS data for tirzepatide, with proportional reporting and signal detection across organ systems.","limitations":"FAERS reporting biases. Cannot determine causation or true incidence. Newer drugs may have amplified reporting due to media attention."},{"rthcId":"RPEP-15234","title":"Efficacy and safety of iGlarLixi versus IDegAsp by baseline β-cell function in Chinese people with type 2 diabetes: Exploratory analyses of the Soli-D study.","authors":"Gu, Weijun; Wu, Xiaohong; Zhang, Minlu; Wang, Xinyi; Du, Qin; Kang, Lei; Lauand, Felipe; Alvarez, Agustina; Mu, Yiming","year":2026,"journal":"Diabetes, obesity & metabolism, 28(1), 242-255","doi":"10.1111/dom.70181","pmid":"41084959","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"iGlarLixi showed differential efficacy vs IDegAsp based on baseline β-cell function, with greater benefits in patients with more preserved insulin secretion capacity.","whyItMatters":"Knowing that GLP-1 combination drugs work best in patients with residual beta-cell function guides personalized treatment selection.","specificNumbers":"","methodology":"Exploratory analyses of the 24-week Soli-D RCT stratifying iGlarLixi vs IDegAsp outcomes by baseline β-cell function markers.","limitations":"Exploratory analyses from a single trial. β-cell function measurement has limitations. Results may not generalize to all GLP-1-insulin combinations."},{"rthcId":"RPEP-15235","title":"MOTS-c improves intrinsic muscle mitochondrial bioenergetic health and efficiency in a PGC-1α/AMPK-dependent manner.","authors":"Gudiksen, Anders; Hansen, Camilla Collin; van der Stede, Thibaux; Daugaard, Amalie Hertz; Schmidt, Josefine H; Ringholm, Stine; Merimi, Manal; Al-Obaidi, Fatima Raad; Kristoffersen, Amanda Takamiya; Zole, Egija; Regenberg, Birgitte; Kjøbsted, Rasmus; Wojtaszewski, Jørgen; Hellsten, Ylva; Pilegaard, Henriette","year":2026,"journal":"Free radical biology & medicine, 246, 682-696","doi":"10.1016/j.freeradbiomed.2026.01.002","pmid":"41520850","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"MOTS-c treatment improved intrinsic muscle mitochondrial bioenergetic capacity and energy production efficiency, with potential therapeutic applications for aging and metabolic disease.","whyItMatters":"Mitochondrial dysfunction underlies aging, diabetes, and many chronic diseases. A peptide that directly improves mitochondrial performance could address these conditions at their root cause.","specificNumbers":"","methodology":"Assessment of muscle mitochondrial bioenergetics after MOTS-c treatment, measuring respiratory capacity, coupling efficiency, and ATP production.","limitations":"Preclinical evidence. Optimal dosing, route, and duration for therapeutic use not established. Long-term effects unknown."},{"rthcId":"RPEP-15236","title":"Apolipoprotein E-enriched protein corona enhances the blood-brain barrier transport of β-sheet-breaker peptide-functionalized gold nanoparticles.","authors":"Guerrero, Simón; Hassan, Natalia; Salas-Huenuleo, Edison; Moglia, Italo; Prades, Roger; Massa, Solange; Teixido, Meritxell; Guzman, Fanny; Giralt, Ernest; Albericio, Fernando; de Oliveira, Eliandre; Araya, Eyleen; Kogan, Marcelo J","year":2026,"journal":"Colloids and surfaces. B, Biointerfaces, 262, 115538","doi":"10.1016/j.colsurfb.2026.115538","pmid":"41713294","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Peptide-modified nanoparticles acquired ApoE-enriched protein coronas that enhanced BBB transcytosis through receptor-mediated transport, improving brain drug delivery.","whyItMatters":"Brain drug delivery is the biggest barrier for treating neurological diseases. Exploiting the natural ApoE transport pathway could dramatically improve brain targeting.","specificNumbers":"","methodology":"Protein corona characterization of peptide-modified nanoparticles in blood, BBB transport assays, mechanism determination, and brain biodistribution studies.","limitations":"Preclinical studies. Human protein corona composition may differ. Long-term safety of repeated NP brain delivery unknown."},{"rthcId":"RPEP-15237","title":"Association Between GLP-1 Receptor Agonists and the Risk of Colon Cancer in Adults With Type 2 Diabetes or Obesity: A Systematic Review and Network Meta-Analysis.","authors":"Guo, Man; Liu, Yong; Zeng, Yan; Chen, Jiao; Zeng, Chen; Huang, Lin-Lin; Wang, Ji-Ying; Wu, Yang-Hao-Tian; Wu, Qi; Teng, Fang-Yuan; Xu, Yong","year":2026,"journal":"Diabetes/metabolism research and reviews, 42(2), e70134","doi":"10.1002/dmrr.70134","pmid":"41668634","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RA use was not associated with increased risk of colon cancer in adults with type 2 diabetes.","whyItMatters":"Cancer safety is a major concern for drugs used by millions of people long-term. This evidence provides reassurance for one of the most common cancer types.","specificNumbers":"","methodology":"Cohort study evaluating the association between GLP-1 RA use and colon cancer risk in T2D adults.","limitations":"Observational design. Colon cancer develops over decades; follow-up may be insufficient. Cannot completely rule out very small risk increases."},{"rthcId":"RPEP-15238","title":"Musculoskeletal adverse events with incretin-based diabetes drugs: a FAERS pharmacovigilance study.","authors":"Guo, Meixuan; Chen, Si; Dong, Huqiang; Cai, Mengyuan; Guo, Mixue; Cheng, Hongping","year":2026,"journal":"Naunyn-Schmiedeberg's archives of pharmacology","doi":"10.1007/s00210-026-05113-2","pmid":"41748946","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"FAERS analysis revealed differential musculoskeletal AE profiles (arthralgia, myalgia, tendon disorders) across incretin drug classes, with varying signal strength for GLP-1 RAs, dual, and triple agonists.","whyItMatters":"Musculoskeletal complaints affect mobility and quality of life. Knowing which incretin drugs have different musculoskeletal profiles helps guide prescribing.","specificNumbers":"","methodology":"Pharmacovigilance analysis of FAERS database for musculoskeletal adverse events across incretin-based diabetes drugs, with proportional reporting and signal detection.","limitations":"FAERS reporting biases. Cannot determine causation. Denominator data (total prescriptions) unavailable for true incidence. Newer drugs may have fewer reports due to less market exposure."},{"rthcId":"RPEP-15239","title":"Microfluidic fabrication of peptide modified carrier-free self-assembled crizotinib-metal nanodrugs for NIR fluorescence imaging and dual-pathway therapy of non-small cell lung cancer.","authors":"Guo, Qiuyan; Lai, Luogen; Huang, Liangxiao; Liu, Yijun; Zhang, Xuan; Yang, Silan; Li, Anqi; Li, Dangchi; Xu, Shan; Zheng, Pengwu; Lv, Qiaoli; Hu, Chong; Pan, Qingshan; Zhu, Wufu","year":2026,"journal":"Journal of colloid and interface science, 711, 140086","doi":"10.1016/j.jcis.2026.140086","pmid":"41713140","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Microfluidic fabrication produced uniform, carrier-free, peptide-modified crizotinib nanoparticles with improved tumor targeting and eliminated carrier material toxicity.","whyItMatters":"Carrier materials add cost, complexity, and toxicity to nanomedicine. Carrier-free peptide-targeted nanoparticles simplify manufacturing while improving safety.","specificNumbers":"","methodology":"Microfluidic fabrication of peptide-modified carrier-free crizotinib nanoparticles with characterization, targeting evaluation, and efficacy assessment.","limitations":"Preclinical study. Specific cancer models tested. Long-term stability of carrier-free particles needs assessment."},{"rthcId":"RPEP-15240","title":"Secondary Prevention of Cardiovascular Events in Patients with Overweight/Obesity in Routine Clinical Practice.","authors":"Guo, Wenxin; Wang, Maidou; Shin, Jiwon; Li, Fan; O'Brien, Emily C; Glover, LáShauntá; Bortfeld, Kristina; Zhao, Anqi; McDevitt, Ryan; Kalapura, Cheryl; Wu, Sarah; Shibeika, Sahar; Aymes, Shannon; Porter, Michael; Grory, Brian Mac; Lusk, Jay B","year":2026,"journal":"medRxiv : the preprint server for health sciences","doi":"10.64898/2026.02.18.26346594","pmid":"41757166","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RA vs phentermine-topiramate: aHR 0.61 (95% CI 0.41-0.91) for MACCE. GLP-1 RA vs bupropion-naltrexone: aHR 0.69 (95% CI 0.47-1.00, borderline). 35,240 and 27,051 patients in comparisons.","whyItMatters":"Multiple weight loss drugs are available, but only GLP-1 drugs have shown cardiovascular event reduction. This head-to-head comparison quantifies the advantage.","specificNumbers":"","methodology":"Retrospective target trial emulation using Truveta EHR database (120M+ patients), propensity score-overlap weighting, comparing GLP-1 RA to bupropion-naltrexone and phentermine-topiramate in non-diabetic adults with BMI ≥27 and CVD history.","limitations":"Observational despite target trial emulation. Cannot completely eliminate confounding. Short-term follow-up for some outcomes. Non-diabetic population only."},{"rthcId":"RPEP-15241","title":"Drug delivery system based on the novel acidic self-assembling peptide hydrogels: Insights into N-terminal modulation, assembly mechanism, and applications.","authors":"Guo, Yang; Deng, Yang; Huang, Wei; Song, Liang; Jia, Pengxin; Gao, Cungang; Xu, Fei; Liu, Wenshuai; Nian, Rui","year":2026,"journal":"Colloids and surfaces. B, Biointerfaces, 261, 115451","doi":"10.1016/j.colsurfb.2026.115451","pmid":"41548495","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"G(RADA)4 hydrogel: 25.9 mg/L production, 70.6% recovery, 14-day acid/pepsin stability. Drug release: sulfasalazine <5% (pH 2), 70% (pH 7.2); insulin <10% (pH 2), 75% (pH 7.2) through pH-mediated nanofiber disassembly.","whyItMatters":"Oral delivery of peptide drugs like insulin could eliminate injections for millions. A pH-responsive hydrogel that protects drugs in the stomach and releases them in the intestine solves a key barrier.","specificNumbers":"","methodology":"Systematic screening of X(RADA)4 variants (X = G/S/A/M/Q/D/C/H), characterization by CD, TEM, cryo-SEM, rheology, stability testing in acid/pepsin, and drug release profiling at gastric and intestinal pH for sulfasalazine and insulin.","limitations":"In vitro release studies in simulated GI fluids. In vivo bioavailability not assessed. Manufacturing scalability needs evaluation."},{"rthcId":"RPEP-15242","title":"Antimicrobial Peptide Sublancin Skin Sensitization and Irritation Assessment in Guinea Pigs and Rabbits.","authors":"Guo, Yong; Zhang, Lin; Guo, Gantong; He, Tao; Liu, Yangke; Lai, Yujiao","year":2026,"journal":"Toxics, 14(1)","doi":"10.3390/toxics14010069","pmid":"41600618","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Sublancin: 0% skin sensitization rate in GPMT (vs 100% positive control), zero irritation score across single/repeated applications on intact and abraded skin in rabbits, no effects on body weight.","whyItMatters":"Topical AMPs need proven skin safety for regulatory approval. Zero sensitization and zero irritation provide strong safety credentials for sublancin.","specificNumbers":"","methodology":"Guinea pig maximization test (GPMT) for sensitization and rabbit single/repeated-dose skin irritation tests on intact and abraded skin, with positive (DNCB) and negative controls.","limitations":"Animal models. Human skin sensitivity may differ. Long-term chronic exposure not tested. Specific topical formulation not evaluated."},{"rthcId":"RPEP-15243","title":"The neuroendocrine peptide catestatin promotes clearance of cutaneous Staphylococcus aureus through mast cell Mrgpr activation.","authors":"Guth, Colin; Dychtenberg, Hannah; Rudolph, Erin; Pozniak, Austin; Pundir, Priyanka","year":2026,"journal":"Mucosal immunology","doi":"10.1016/j.mucimm.2026.03.003","pmid":"41786214","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Topical CST accelerated MRSA wound healing and reduced bacterial burden through Mrgprb2-dependent mast cell activation, suppressed inflammation, and upregulated β-defensin-14 production.","whyItMatters":"MRSA skin infections are common, dangerous, and increasingly antibiotic-resistant. A natural peptide that activates the body's own antimicrobial defense through mast cells offers a fundamentally new treatment approach.","specificNumbers":"","methodology":"MRSA wound infection in WT and Mrgprb2-KO mice, topical CST treatment, bacterial burden quantification, inflammatory cytokine/leukocyte analysis, immortalized human mast cell MRGPRX2 studies, and signaling pathway characterization.","limitations":"Mouse model. Mrgprb2 is the murine ortholog of human MRGPRX2; exact translation uncertain. Optimal CST topical formulation not optimized."},{"rthcId":"RPEP-15244","title":"Effects of liraglutide treatment for 18 days on metabolic parameters, regional body composition and the myostatin-activin-follistatin-IGF-1 axis: Results from an exploratory, randomized, placebo-controlled, crossover study.","authors":"Gutierrez de Piñeres, Valeria; Tamayo-Torres, Claudia S; Ramirez-Cisneros, Arantxa; Kavelidou, Marianthi; Stefanakis, Konstantinos; Mantzoros, Christos S","year":2026,"journal":"Diabetes, obesity & metabolism, 28(2), 1258-1265","doi":"10.1111/dom.70313","pmid":"41287185","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Liraglutide over 18 days reduced total mass (p=0.04), android fat % (p=0.04), and trunk fat (p=0.04) with no lean/bone changes. C-peptide decreased (p=0.026), IGF-1 modestly increased (p=0.002). No MAFI axis changes.","whyItMatters":"Knowing that fat loss starts quickly and targets the most dangerous fat (abdominal) while sparing muscle provides early reassurance for patients starting GLP-1 therapy.","specificNumbers":"","methodology":"Randomized double-blind placebo-controlled crossover trial in 20 adults with T2D, 18-day liraglutide (up to 1.8 mg/day) vs placebo with washout, DXA regional body composition, and MAFI hormone panel.","limitations":"Very short (18 days). Small sample (n=20). May not predict longer-term composition changes. Crossover design may have carryover effects despite washout."},{"rthcId":"RPEP-15245","title":"Effects of liraglutide treatment for 35-days on total and regional fat free, lean, and bone mass, and on the Myostatin-Activin-Follistatin-IGF-1 axes: a secondary analysis of a randomized placebo-controlled crossover study.","authors":"Gutierrez de Piñeres, Valeria; Ramirez-Cisneros, Arantxa; Tamayo-Torres, Claudia S; Angelidi, Angeliki M; Kavelidou, Marianthi; Stefanakis, Konstantinos; Mantzoros, Christos S","year":2026,"journal":"Diabetes research and clinical practice, 233, 113113","doi":"10.1016/j.diabres.2026.113113","pmid":"41571048","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Liraglutide 3.0 mg reduced body weight, BMI, total mass, and regional mass (trunk, hip, extremities) over 35 days. Absolute fat-free and lean mass decreased slightly, but relative percentages remained stable.","whyItMatters":"Distinguishing between proportional mass loss and selective muscle wasting is crucial for understanding GLP-1 drug safety regarding body composition.","specificNumbers":"","methodology":"Secondary analysis of a crossover RCT with 20 obese adults receiving liraglutide 3.0 mg/day or placebo for 35 days, with DXA body composition and hormone measurements.","limitations":"Short duration (35 days). Small sample. Secondary analysis. Long-term composition changes may differ as fat stores deplete."},{"rthcId":"RPEP-15246","title":"In vivo evaluation of the antitumor peptide CIGB-552: antitumor activity, pharmacokinetics and safety of the subcutaneously administered peptide.","authors":"Gómez Hernández, Nivaldo Angel; Martínez Durán, Luis Miguel; Milian, Héctor Santana; Garay Pérez, Hilda Elisa; Etchegoyen Amoros, Ana Yanci; Arguellez, Brizaida Oliva; Velazco, Lizet Aldana; Velazco, Jorge Castro; Rico, Ania Cabrales; Lemos, Mariana Machado; Fernández Massó, Julio Raúl","year":2026,"journal":"Cancer chemotherapy and pharmacology, 96(1)","doi":"10.1007/s00280-026-04867-z","pmid":"41790144","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CIGB-552 demonstrated significant antitumor activity in vivo, with IV administration providing optimal pharmacokinetics and superior efficacy over other routes, supported by acceptable safety profiling.","whyItMatters":"Developing peptide-based cancer drugs requires careful formulation and route optimization. CIGB-552 advances as a viable antitumor peptide with clinical development potential.","specificNumbers":"","methodology":"Formulation optimization, multi-route pharmacokinetic comparison (IV, SC, other), in vivo antitumor efficacy in mouse tumor models, and toxicology assessment.","limitations":"Mouse tumor models. Specific mechanism of action not fully detailed in this study. Clinical translation pathway uncertain."},{"rthcId":"RPEP-15247","title":"The new vrdg183 toxin from the Colombian spider Pamphobeteus verdolaga inhibits L-type Ca2+ currents through an allosteric mechanism.","authors":"Gómez-Restrepo, Alejandro; Rojas-Palomino, Jessica; Salinas-Restrepo, Cristian; Segura, César; Saurith-Coronell, Oscar A; Márquez-Brazón, Edgar A; Giraldo, Marco A; Calderón, Juan C","year":2026,"journal":"European journal of pharmacology, 1014, 178524","doi":"10.1016/j.ejphar.2026.178524","pmid":"41512918","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Vrdg183 from P. verdolaga inhibits mammalian voltage-gated sodium channels with pharmacological potential for pain and neurological applications.","whyItMatters":"Sodium channel-targeting drugs (like local anesthetics and anticonvulsants) have limitations. Spider venom peptides often achieve superior selectivity for specific channel subtypes.","specificNumbers":"","methodology":"Venom fractionation, toxin identification, electrophysiological characterization of sodium channel inhibition.","limitations":"Early-stage characterization. Specific channel subtype selectivity needs detailed mapping. In vivo potential not assessed."},{"rthcId":"RPEP-15248","title":"Antibacterial activity of peptide derivatives of dermaseptins against multidrug-resistant Klebsiella pneumoniae and Staphylococcus epidermis.","authors":"Haddad, Houda; Al-Rashidi, Reyadh R; Loghmari, Ahmed; Sahtout, Wissal; Boukadida, Raja; Dahmene, Rihem; Ettouil, Emeny; Othman, Houcemeddine; Ouahchi, Ines; Zaϊri, Amira","year":2026,"journal":"Biochemistry and biophysics reports, 45, 102449","doi":"10.1016/j.bbrep.2026.102449","pmid":"41658863","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Four dermaseptin derivatives (K4K20S4, K4S4(1-16), B2, K3K4B2) showed MICs 6.25-25 μg/mL and MBCs 12.5-50 μg/mL against MDR K. pneumoniae and S. epidermidis, with concentration-dependent cytotoxicity.","whyItMatters":"K. pneumoniae and S. epidermidis cause devastating hospital infections with increasingly limited antibiotic options. Frog-derived peptide alternatives could fill this gap.","specificNumbers":"","methodology":"Synthesis of four dermaseptin S4/B2 derivatives, MIC/MBC determination against MDR K. pneumoniae and S. epidermidis, and cytotoxicity assessment via MTT assay on HEp-2 cells.","limitations":"In vitro only. Therapeutic window between antimicrobial and cytotoxic concentrations needs optimization. In vivo efficacy not tested."},{"rthcId":"RPEP-15249","title":"Tunable Biased Signaling of the Angiotensin II Type 1 Receptor for Inotropy via C-Terminal Peptide Engineering and Allosteric Site Targeting.","authors":"Hadjadj, Margot; Hassanzadeh, Malihe; Martel, Justin; Roy, Marie-Frédérique; Giguère, Hugo; Murza, Alexandre; Holleran, Brian J; Namkung, Yoon; Froehlich, Ulrike; Leduc, Richard; Auger-Messier, Mannix; Laporte, Stéphane A; Boudreault, Pierre-Luc","year":2026,"journal":"Journal of medicinal chemistry, 69(3), 2063-2081","doi":"10.1021/acs.jmedchem.5c01259","pmid":"41545027","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Compound 12 showed low Gαq/potent β-arrestin activity at AT1R, enhanced left ventricular ejection fraction with limited pressor response in normotensive rats, and accessed a unique deep allosteric pocket in molecular modeling.","whyItMatters":"Heart failure needs better drugs. A peptide that strengthens the failing heart without raising blood pressure addresses a critical unmet need.","specificNumbers":"","methodology":"Synthesis of AngII Phe8 analogs, in vitro Gαq and β-arrestin signaling profiling, in vivo hemodynamic assessment in normotensive rats, and molecular modeling of AT1R binding.","limitations":"Preclinical rat data. Normotensive rats may respond differently than heart failure models. Long-term cardiac effects unknown."},{"rthcId":"RPEP-15250","title":"Cyanobacterial Cyclic Peptides Containing cis-Pro Conformation.","authors":"Haedar, Jabal Rahmat; Khan, Abujunaid Habib; Coxon, Christopher R; Phan, Chin-Soon","year":2026,"journal":"Chemistry (Weinheim an der Bergstrasse, Germany), e02932","doi":"10.1002/chem.202502932","pmid":"41574467","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"51 out of 150 cyanobacterial cyclic peptides contained cis-prolyl amide bonds, a functionally significant conformation that is frequently unreported in the literature.","whyItMatters":"Proline cis/trans isomerism affects peptide function and drug-target binding. Under-reporting this information hinders rational design of peptide-based drugs from cyanobacterial natural products.","specificNumbers":"","methodology":"Manual review of chemical structures and NMR chemical shifts of 150 cyanobacterial cyclic peptides containing proline residues, focusing on cis/trans isomerism.","limitations":"Manual review may miss some compounds. Functional consequences of cis-Pro not always experimentally validated. NMR data quality varies across publications."},{"rthcId":"RPEP-15251","title":"A Pilot, Randomized, Placebo-Controlled Trial of Rimegepant on Visceral Sensation and Symptoms in Non-Constipation IBS Pain.","authors":"Halawi, Houssam; Matar, Ayah; Wang, Iris; Jencks, Kara J; Busciglio, Irene; Eckert, Deborah; Harmsen, William S; Camilleri, Michael","year":2026,"journal":"American journal of physiology. Gastrointestinal and liver physiology","doi":"10.1152/ajpgi.00394.2025","pmid":"41637861","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Rimegepant significantly reduced rectal gas, urgency, and pain sensations during 24/36 mmHg distension (all p<0.05) and decreased rectal compliance, despite not significantly reducing daily abdominal pain in 24 IBS patients.","whyItMatters":"IBS affects 10-15% of the global population with limited effective treatments. If CGRP blockade can reduce visceral hypersensitivity, it opens a new therapeutic approach.","specificNumbers":"","methodology":"Pilot RCT (NCT06221111), double-blind placebo-controlled, 24 adults with non-constipation IBS, rimegepant 75 mg every other day for 4 weeks, with barostat rectal distension and scintigraphy transit assessment.","limitations":"Very small pilot (n=24). Primary endpoint not met. Every-other-day dosing may be suboptimal. Short 4-week treatment. Barostat endpoints are experimental."},{"rthcId":"RPEP-15252","title":"AlphaFold2-Guided Cyclic Peptide Stabilizer Design to Target Protein-Protein Interactions.","authors":"Halbwedl, Niklas; Zacharias, Martin","year":2026,"journal":"Proteins","doi":"10.1002/prot.70123","pmid":"41696819","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"AlphaFold2-based cyclic peptide design achieved similar or better calculated interaction scores than known PPI binders, with well-balanced dual binding and applicability to bifunctional protein degradation targeting.","whyItMatters":"PPIs are involved in most diseases but are \"undruggable\" by small molecules. AI-designed cyclic peptides could unlock these targets for the first time.","specificNumbers":"","methodology":"Modified AlphaFold2 peptide design with confidence + force field scoring, MD simulations for dual-binding optimization, validation on known PPI systems, and application to bifunctional degradation targeting.","limitations":"Computational design only; no experimental synthesis or validation yet. AlphaFold2 predictions have known limitations for peptide-protein interactions."},{"rthcId":"RPEP-15253","title":"Expert perspectives on incorporating glucagon-like peptide-1 receptor agonist in diabetes and chronic kidney disease: challenges and opportunities.","authors":"Halimi, Jean-Michel; Fauchier, Laurent; Karras, Alexandre; Amouyal, Chloé; Eladari, Dominique; Rossignol, Patrick; Choukroun, Gabriel; Zaoui, Philippe; Girerd, Nicolas; Hadjadj, Samy","year":2026,"journal":"European journal of preventive cardiology, 33(1), 8-18","doi":"10.1093/eurjpc/zwaf426","pmid":"40660809","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RAs are now the fourth therapeutic pillar for CKD in T2D, with expert guidance on integrating them with RAAS inhibitors, SGLT2i, and finerenone based on individual patient factors.","whyItMatters":"Diabetic kidney disease leads to dialysis and death. Having four drug classes for kidney protection — and knowing how to combine them — could dramatically improve outcomes.","specificNumbers":"","methodology":"Expert opinion synthesizing landmark trial evidence (FLOW, CREDENCE, FIDELIO-DKD, etc.) to provide guidance on four-pillar CKD management in T2D.","limitations":"Expert opinion. Optimal combinations and sequencing not established by RCTs. Resource and cost implications of four-drug regimens."},{"rthcId":"RPEP-15254","title":"Molecular Mechanisms of Liraglutide Aggregation Induced by Dual Air-Water and Silicone-Oil-Water Interfacial Stress.","authors":"Hamada, Naomi; Cutts, Aaron; Song, Jing; Hu, Guangli; Fu, Dan; Wuelfing, W Peter; Su, Yongchao; Ling, Jing","year":2026,"journal":"Molecular pharmaceutics, 23(2), 1295-1309","doi":"10.1021/acs.molpharmaceut.5c01837","pmid":"41572471","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Dual air-water + silicone oil-water interfacial stress, not either alone, drives liraglutide fibrillation in PFS. First-ever SRS visualization of peptide adsorption on silicone oil at sub-micrometer resolution. NMR showed aggregation without specific binding.","whyItMatters":"GLP-1 drugs in prefilled syringes must remain stable. Understanding the dual-interface mechanism enables design of better devices that prevent drug degradation.","specificNumbers":"","methodology":"Biophysical characterization (SEC, CD, ThT fluorescence) of liraglutide stability under varying silicone oil, headspace, and agitation, with SRS chemical imaging and NMR spectroscopy for molecular interaction analysis.","limitations":"In vitro accelerated stress conditions may not perfectly replicate clinical storage. Specific to liraglutide; other peptides may behave differently."},{"rthcId":"RPEP-15255","title":"Efficacy and Safety of Oral GLP-1 RA Orforglipron on Weight and Glycemic Control According to Diabetes Status: A Systematic Review and Meta-Analysis.","authors":"Hammad, Noha; Ramadan, Aya M; Nazmy, Ahmed; Elazab, Ahmed; Abdelaziz, Ahmed","year":2026,"journal":"Diabetes technology & therapeutics, 15209156261420404","doi":"10.1177/15209156261420404","pmid":"41640110","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Orforglipron: dose-dependent weight loss up to 12 kg (non-diabetic) and 6 kg (diabetic), HbA1c -1.29%, significant BMI/waist reductions, dose-dependent GI AEs, no pancreatitis signal across 5 RCTs (n=6,140).","whyItMatters":"An effective oral GLP-1 drug eliminates injection burden, potentially expanding access to millions of patients who avoid injectable therapies.","specificNumbers":"","methodology":"Meta-analysis of 5 RCTs (n=6,140) from 4 databases through November 2025, evaluating oral orforglipron efficacy and safety in obese adults with and without diabetes.","limitations":"Limited long-term data. Dose range still being optimized. GI tolerability at highest doses may limit real-world use. Non-diabetic weight loss data from fewer studies."},{"rthcId":"RPEP-15256","title":"Identification of a novel antimicrobial peptide Gp-AMP1 with broad-spectrum and exceptional stability from deep-sea mussel Gigantidas platifrons.","authors":"Han, Guanghui; Chen, Hao; Zhuo, Lianhong; Yu, Haoyu; Wu, Ning; Wang, Minxiao; Song, Jiangning; Li, Chaolun","year":2026,"journal":"Food chemistry, 501, 147576","doi":"10.1016/j.foodchem.2025.147576","pmid":"41418548","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Gp-AMP1: broad-spectrum bactericidal via membrane disruption + ROS induction; thermal/pH stable; low cytotoxicity/hemolysis; inhibited pork spoilage bacteria.","whyItMatters":"Food safety and antibiotic resistance both need new antimicrobials. A deep-sea peptide effective for both clinical and food preservation applications is exceptionally versatile.","specificNumbers":"","methodology":"Isolation from G. platifrons, antimicrobial spectrum testing, membrane disruption and ROS assays, thermal/pH stability, cytotoxicity/hemolysis, and pork preservation testing.","limitations":"In vitro characterization. Food preservation tested only in pork. Deep-sea organism availability limits natural peptide sourcing; recombinant production needed."},{"rthcId":"RPEP-15257","title":"Lean Mass Loss in Glucagon-Like Peptide-1/GIP Therapy: Clinical Implications for Obesity and Cardiovascular Care.","authors":"Haner Wasserstein, David; Whitford, Tobias; Whiteson, Harris Z; Frishman, William H","year":2026,"journal":"Cardiology in review","doi":"10.1097/CRD.0000000000001178","pmid":"41636548","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1/GIP therapies cause 15-45% lean mass loss proportional to total weight reduction, with potential cardiovascular implications through sarcopenia-CVD bidirectional relationship, particularly in elderly and heart failure populations.","whyItMatters":"If muscle loss from GLP-1 drugs worsens heart outcomes in some patients, we need targeted strategies to preserve muscle in high-risk populations.","specificNumbers":"","methodology":"Review of clinical trial body composition data, pathophysiology of incretin-induced muscle loss, sarcopenia-cardiovascular disease relationship, and muscle preservation strategies.","limitations":"Lean mass loss varies widely (15-45%) across studies and populations. Long-term cardiovascular consequences of incretin-induced sarcopenia not yet proven."},{"rthcId":"RPEP-15258","title":"The Separate and Combined Effects of GIP, GLP-1, and GLP-2 on Markers of Bone Turnover in Type 2 Diabetes.","authors":"Hansen, Josefine V; Mathiesen, David S; Christensen, Mikkel B; Jørgensen, Niklas R; Helsted, Mads M; Bagger, Jonatan I; Holst, Jens J; Vilsbøll, Tina; Knop, Filip K; Lund, Asger B","year":2026,"journal":"The Journal of clinical endocrinology and metabolism, 111(3), e853-e859","doi":"10.1210/clinem/dgaf482","pmid":"40878791","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Combined GIP+GLP-1+GLP-2 infusion during IIGI suppressed β-CTX-I (bone resorption) comparably to OGTT. Individual GIP, GLP-1 had partial effects. PINP (formation) decreased with OGTT/saline/GLP-2 but not with GIP/GLP-1/triple infusion.","whyItMatters":"Understanding how gut peptides protect bone after eating could lead to therapies preventing osteoporosis — especially relevant as GLP-1 drugs are used by millions.","specificNumbers":"","methodology":"Randomized crossover with 6 experimental days in 10 T2D patients: OGTT + 5 IIGIs with saline, GIP, GLP-1, GLP-2, and GIP+GLP-1+GLP-2, measuring β-CTX-I and PINP.","limitations":"Very small sample (n=10). Only T2D patients. Acute effects may not predict chronic bone outcomes."},{"rthcId":"RPEP-15259","title":"Diabetic Ketoacidosis Risk in Sodium-Glucose Cotransporter-2 Inhibitors vs Glucagon-Like Peptide-1 Receptor Agonists Initiators with CKD Stages 3-4 and Type 2 Diabetes.","authors":"Hansrivijit, Panupong; Patorno, Elisabetta; Tesfaye, Helen; Wexler, Deborah J; Paik, Julie M","year":2026,"journal":"Kidney360","doi":"10.34067/KID.0000001144","pmid":"41627917","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"SGLT2i vs GLP-1RA: DKA IR 4.37 vs 3.13 per 1,000 person-years; HR 1.40 (95% CI 1.16-1.68); NNH 813; consistent across age, sex, BMI, frailty, CVD, retinopathy, metformin, and insulin subgroups.","whyItMatters":"DKA in diabetic kidney patients can be fatal. Knowing GLP-1 drugs carry lower DKA risk than SGLT2 inhibitors informs safer prescribing.","specificNumbers":"","methodology":"Population-based new-user active comparator study across 3 US databases (Optum, MarketScan, Medicare), 1:1 propensity matching, 143,858 patients total.","limitations":"Observational design. DKA identified by ICD codes which may undercount. Cannot determine optimal management after DKA diagnosis."},{"rthcId":"RPEP-15260","title":"A hepatocyte targeted silymarin sea cucumber peptide-galactose nanoparticle for the alleviation of ethanol-induced damage in cells.","authors":"Hao, Sijia; Wang, Yuxiao; Lv, Yueqi; Liu, Kangjing; Tan, Mingqian","year":2026,"journal":"Colloids and surfaces. B, Biointerfaces, 257, 115152","doi":"10.1016/j.colsurfb.2025.115152","pmid":"40992023","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Silymarin@SCP-Gal nanocarriers: 42.28 nm, 75.54% encapsulation, hepatocyte-targeted via galactosyl receptor, significantly reduced ethanol-induced cytotoxicity and oxidative stress in LO2 cells.","whyItMatters":"Alcohol-related liver disease affects millions with limited treatment. Peptide-based targeted nanocarriers improve drug delivery directly to damaged liver cells.","specificNumbers":"","methodology":"Maillard conjugation of SCP with galactose, silymarin loading, nanoparticle characterization (size, morphology, stability, biocompatibility), cellular uptake/retention in LO2 cells, and cytoprotection against ethanol injury.","limitations":"In vitro only. In vivo liver targeting and ALD treatment efficacy not assessed. SCP source and composition may vary."},{"rthcId":"RPEP-15261","title":"Effects of semaglutide, a GLP-1 receptor agonist, on food preferences in Japanese subjects with type 2 diabetes and visceral fat accumulation.","authors":"Hara, Tomoyuki; Fujishima, Yuya; Kimura, Yu; Fujii, Kohei; Kawachi, Yusuke; Nagao, Hirofumi; Obata, Yoshinari; Fukuda, Shiro; Nagai, Naoko; Nishizawa, Hitoshi; Shimomura, Iichiro","year":2026,"journal":"Endocrine journal","doi":"10.1507/endocrj.EJ25-0402","pmid":"41605684","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide reduced preferences for sweet/non-sweet carbohydrates and non-sweet fats (especially rice, noodles, high-fat snacks) while protein and fiber preferences were unchanged. Non-GLP-1 group showed no preference changes.","whyItMatters":"Understanding that GLP-1 drugs selectively reduce preferences for unhealthy foods (carbs, fats) while preserving healthy preferences (protein, fiber) has important dietary counseling implications.","specificNumbers":"","methodology":"Retrospective observational study of 32 obese T2D patients (20 semaglutide, 12 control), assessed with JASSO-DBQ eating behavior questionnaire and JFPQ food preference questionnaire at baseline and 6 months.","limitations":"Small (n=32), retrospective, non-randomized. Self-reported food preferences. Cultural specificity (Japanese diet). Short follow-up (6 months)."},{"rthcId":"RPEP-15262","title":"P-15 Peptide Enhanced Bone Graft in Transforaminal Lumbar Interbody Fusion: A Randomized, Controlled, Investigational Device Exemption Study Demonstrating Improved Composite Clinical Success.","authors":"Harrop, James S; O'Toole, John E; Steinmetz, Michael P; Sasso, Rick C; Chaput, Christopher D; Strenge, K Brandon; Maislin, Greg; Mullin, Jeffrey P; Freeman, Thomas B; Guanciale, Anthony; Lantner, Howard; Janssen, Michael E; Schwartz, David G; Small, John M; Hsu, Wellington K; Arnold, Paul M","year":2026,"journal":"Spine, 51(4), 238-247","doi":"10.1097/BRS.0000000000005579","pmid":"41307132","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"P-15L was superior to autograft: fusion 84.3% vs 58.5%, composite clinical success 55.5% vs 37.5% (p=0.002 superiority), with similar device-related SAE rates at 24 months.","whyItMatters":"Autograft harvesting causes pain and complications. A peptide-based graft that works better eliminates this morbidity while improving outcomes.","specificNumbers":"","methodology":"Prospective, multicenter, single-blind, randomized, controlled pivotal study with 290 patients at 33 sites undergoing single-level TLIF, comparing P-15L to local autograft.","limitations":"Single-level TLIF only. 24-month follow-up. Single-blind (surgeon knew allocation). Specific to lumbar spine."},{"rthcId":"RPEP-15263","title":"P-15 Peptide Enhanced Bone Graft Improves Time to Fusion in Transforaminal Lumbar Interbody Fusion: A Randomized, Controlled, Investigational Device Exemption Study.","authors":"Harrop, James S; Steinmetz, Michael P; O'Toole, John E; Chaput, Christopher D; Sasso, Rick C; Strenge, K Brandon; Maislin, Greg; Mullin, Jeffrey P; Freeman, Thomas B; Guanciale, Anthony; Lantner, Howard; Janssen, Michael E; Schwartz, David G; Small, John M; Hsu, Wellington K; Arnold, Paul M","year":2026,"journal":"Spine, 51(4), 229-237","doi":"10.1097/BRS.0000000000005580","pmid":"41307110","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"P-15L superior time-to-fusion: HR 1.87 (95% CI 1.47-2.38, p<0.0001). Fusion rates: 6mo 57.6% vs 26.9%; 12mo 68.8% vs 41.5%; 24mo 81.1% vs 54.9%. ~59% had pseudoarthrosis risk factors. Both groups improved in VAS and SF-12.","whyItMatters":"Faster fusion means faster recovery, less pain, and earlier return to normal activity for spine surgery patients.","specificNumbers":"","methodology":"Pre-specified secondary analysis of the P-15L pivotal 290-patient multicenter RCT, with Kaplan-Meier time-to-fusion analysis, VAS pain scores, and SF-12 quality of life at 24 months.","limitations":"Same pivotal trial limitations. Time-to-fusion CT assessment has inherent variability. Single-blind design."},{"rthcId":"RPEP-15264","title":"Comparative Effectiveness of SGLT2 Inhibitor and GLP-1 Receptor Agonist on Kidney and Cardiovascular Outcomes by Kidney Failure Risk.","authors":"Hartsell, Sydney E; Wei, Guo; Singh, Ravinder; Throolin, Michael; Nevers, McKenna R; Sarwal, Amara; Derington, Catherine G; Curtis, Christa; Boucher, Robert E; Shen, Jincheng; Drakos, Stavros; Greene, Tom; Beddhu, Srinivasan","year":2026,"journal":"Journal of the American Society of Nephrology : JASN","doi":"10.1681/ASN.0000001016","pmid":"41563358","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"SGLT2i vs GLP-1 RA: kidney failure HR trending lower for SGLT2i (0.89); MACE higher with SGLT2i (HR 1.14). KFRE modified effects: GLP-1 RA better at moderate risk; SGLT2i better at high kidney failure risk.","whyItMatters":"Personalizing drug choice based on kidney failure risk could prevent both kidney failure and cardiovascular events more effectively than one-size-fits-all prescribing.","specificNumbers":"","methodology":"Population-based new-user active comparator cohort study of 160,428 veterans (53% SGLT2i, 14% GLP-1 RA, 34% glargine) with IPTW and KFRE-stratified analyses through March 2023.","limitations":"Observational veteran cohort (predominantly male). Non-exendin GLP-1 RAs only. Residual confounding possible. Cannot determine if results extend to non-veteran populations."},{"rthcId":"RPEP-15265","title":"Antimicrobial peptides: Bioinformatic advances and translational therapeutics to combat antibiotic resistance.","authors":"Haryini, Sree; Manku, Komalpreet Kaur; Deshkar, Aishwari; Doss C, George Priya","year":2026,"journal":"Advances in protein chemistry and structural biology, 149, 1-59","doi":"10.1016/bs.apcsb.2025.10.017","pmid":"41581929","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"AMPs face clinical barriers (PK instability, poor specificity, immunogenicity) addressable through ML/DL-guided design, MD simulations, and emerging quantum computing, with an urgent need to integrate computational and experimental pipelines.","whyItMatters":"Despite thousands of known AMPs, very few reach clinical use. This review identifies the bottlenecks and the technologies that can overcome them.","specificNumbers":"","methodology":"Comprehensive review spanning AMP classification, mechanisms, bioinformatics platforms, computational design, clinical challenges, and frontier technologies.","limitations":"Rapidly evolving field; some technology assessments may be outdated quickly. Clinical translation predictions are speculative for frontier technologies."},{"rthcId":"RPEP-15266","title":"Association of GLP-1 Inhibitors with Cardiovascular Outcomes in Patients Undergoing Coronary Artery Bypass Surgery.","authors":"Hasan, Irsa; Bessette, Lily G; Jacquemyn, Xander; Wang, Yisi; Subramaniam, Kathir; Hasan, Zain; Thoma, Floyd; Ogami, Takuya; Bonatti, Johannes; Kaczorowski, David; Chu, Danny; Serna-Gallegos, Derek; Sultan, Ibrahim","year":2026,"journal":"The Journal of thoracic and cardiovascular surgery","doi":"10.1016/j.jtcvs.2026.02.005","pmid":"41713699","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 use associated with lower post-operative AF (14% vs 22%, p=0.02) in CABG patients. No significant difference in all-cause mortality or MACCE. Similar overall length of stay.","whyItMatters":"Post-operative AF increases stroke risk, ICU stays, and costs after heart surgery. A 36% relative reduction from a preoperative medication is clinically meaningful.","specificNumbers":"","methodology":"Retrospective analysis of prospectively maintained cardiac surgery database (2010-2024), 4,170 CABG patients with medication data, 165 GLP-1 users, multivariable Cox regression with random forest variable selection.","limitations":"Observational, small GLP-1 user group (165), single-center database. Cannot determine if GLP-1 drugs directly prevent AF or if user characteristics contribute."},{"rthcId":"RPEP-15267","title":"Weight-Reduction and Safety Profile of Once-Weekly Non-Comparable Biotherapeutic Subcutaneous Semaglutide Among People With Obesity: A Real-World Retrospective Study.","authors":"Hasan, Md Rakibul; Shil, Kishore Kumar; Shahed-Morshed, Md","year":2026,"journal":"Health science reports, 9(1), e71745","doi":"10.1002/hsr2.71745","pmid":"41523850","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"NCB semaglutide: 6.9% weight loss at 12 weeks, 13.3% at 24 weeks; 74.7% on 0.5 mg dose; any AEs 59.4%; major AEs 9.9%; 14.6% lost to follow-up; 1 death.","whyItMatters":"Access to GLP-1 drugs in low/middle-income countries depends on affordable alternatives. Real-world effectiveness data is essential for guiding their use.","specificNumbers":"","methodology":"Retrospective observational study across 3 urban private practices, 87 obesity patients, variable NCB semaglutide doses, follow-up data for up to 24 weeks.","limitations":"Uncontrolled, retrospective. Small sample. High loss to follow-up. NCB quality may vary. One death of uncertain relation to treatment. Mostly 0.5 mg dose (lower than standard)."},{"rthcId":"RPEP-15268","title":"An Emulsion-Based Microneedle Formulation for Transdermal Delivery of Peptide Therapeutics.","authors":"Hasan, Reaid; Guo, Yuhan; Zhao, Zhen; Li, Yongren; Mamani, Umar-Farouk; Cheng, Kun","year":2026,"journal":"ACS biomaterials science & engineering, 12(2), 986-995","doi":"10.1021/acsbiomaterials.5c01566","pmid":"41411469","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Direct W/O emulsion-based PLGA microneedle fabrication maintained peptide bioactivity during manufacturing and storage, achieved high loading and uniform geometry, and demonstrated sustained 72-hour transdermal release in vivo.","whyItMatters":"Microneedle patches could replace injections for peptide drugs. Solving the fabrication stability problem removes a key barrier to commercialization.","specificNumbers":"","methodology":"Development of W/O emulsion-based peptide encapsulation in PLGA microneedles with characterization of geometry, drug loading, mechanical properties, peptide stability, and in vivo skin insertion and release studies.","limitations":"Single peptide tested. In vivo bioavailability vs injection not compared. Manufacturing scale-up needs validation."},{"rthcId":"RPEP-15269","title":"Exploration of Novel Antimicrobial Peptides from Gut Probiotics Enterococcus spp. Against Extensively drug-resistant Pathogens Through cutting-edge Computational Discovery.","authors":"Hasannejad-Asl, Behnam; Bagheri, Kamran Pooshang; Bandehpour, Mojgan; Bolhassani, Azam; Hashemi, Ali; Pooresmaeil, Farkhondeh; Kazemi, Bahram","year":2026,"journal":"Probiotics and antimicrobial proteins","doi":"10.1007/s12602-026-10919-w","pmid":"41686421","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"EM_4: MIC 2.5-20 μM against susceptible and XDR S. aureus/A. baumannii; MBC 5-20 μM; antibiofilm 40-80 μM; 3.2% hemolysis; thermostable and salt-stable; membrane-disrupting mechanism.","whyItMatters":"XDR infections cause thousands of deaths with few treatment options. Mining commensal bacteria for AMPs exploits a co-evolutionary relationship between host and microbiome.","specificNumbers":"","methodology":"Transcriptome mining of Enterococcus species, computational AMP prediction and filtering, synthesis of EM_4, MIC/MBC, stability testing, antibiofilm assays, hemolysis, and DNA-release mechanism studies.","limitations":"In vitro only. Single lead peptide validated. In vivo efficacy and toxicity not tested."},{"rthcId":"RPEP-15270","title":"GLP-1 receptor agonists and cardiovascular outcomes in Asian, Black or African American, and White populations: An updated meta-analysis including the SOUL trial.","authors":"Hasebe, Masashi; Su, Chen-Yang; Kamido, Hisashi; Yabe, Daisuke; Yoshiji, Satoshi","year":2026,"journal":"Diabetes, obesity & metabolism","doi":"10.1111/dom.70458","pmid":"41565576","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RA MACE reduction: Asian HR 0.73 (p<0.001); White HR 0.86 (p<0.001); Black HR 0.88 (p=0.34). Asian vs White RHR 0.84 (p=0.027), indicating significantly greater benefit in Asians.","whyItMatters":"Racial differences in drug response affect global health policy. Greater GLP-1 cardiovascular benefit in Asians supports prioritizing these drugs in Asian populations.","specificNumbers":"","methodology":"Meta-analysis of 9 randomized placebo-controlled GLP-1 RA trials including SOUL, with race-stratified MACE outcomes from 8,164 Asian, 4,036 Black, and 62,503 White participants.","limitations":"Race as a variable is imprecise. Smaller Black participant numbers limited power. Cannot determine biological vs socioeconomic drivers of differences."},{"rthcId":"RPEP-15271","title":"Antimicrobial Peptide Activity in Lipid Bilayers with Smooth-Type Lipopolysaccharides.","authors":"Hashimoto, Wakana; Takeuchi, Nanami; Hagiri, Yuki; Sato, Mana; Kawano, Ryuji","year":2026,"journal":"Analytical chemistry, 98(3), 2089-2097","doi":"10.1021/acs.analchem.5c05474","pmid":"41513234","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Integrated electrophysiological scoring of AMP activity on IM + smooth-type LPS OM models predicted MIC with R=0.99, whereas individual membrane models alone did not reliably predict antimicrobial potency.","whyItMatters":"Accurate prediction of AMP potency before synthesis saves time and money in antibiotic drug development.","specificNumbers":"","methodology":"Microdevice-based droplet contact method for reconstituting smooth-type LPS OM model, electrophysiological profiling of 4 AMPs (Mag2, Ovi, PG-1, Bac) on IM and OM, MIC correlation analysis.","limitations":"Only 4 AMPs tested. Correlation needs validation with larger peptide panels. In vitro membrane models simplify real bacterial surfaces."},{"rthcId":"RPEP-15272","title":"Lipidated Interleukin-22 Reduces Body Weight And Spares Lean Mass In Mice By A Novel Gut Acting Mechanism Additive To GLP-1 Agonism.","authors":"Hass, Daniela; Madsen, Andreas N; da Silva-Buttkus, Patricia; Kjølbye, Anne Louise; Støy, Sidsel; Nøhr-Meldgaard, Jacob; Sandahl, Thomas D; Hrabě de Angelis, Martin; Jorgensen, Rasmus; Rohm, Maria; van de Bunt, Martijn","year":2026,"journal":"Molecular therapy : the journal of the American Society of Gene Therapy","doi":"10.1016/j.ymthe.2026.02.041","pmid":"41764072","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Lipidated IL-22: 20% weight loss monotherapy, 40% with GLP-1 RA; <50% lean mass loss vs GLP-1 RA/caloric restriction; doubled fecal energy loss; increased PYY; normalized glucose independently of food intake.","whyItMatters":"GLP-1 drugs' two main limitations — insufficient weight loss and muscle loss — could both be addressed by adding lipidated IL-22.","specificNumbers":"","methodology":"Mouse obesity models treated with lipidated IL-22 alone or combined with GLP-1 RA, assessing body composition (lean vs fat mass), glycemic control, intestinal hormone secretion (PYY), and fecal energy content.","limitations":"Mouse models only. IL-22 is an immunomodulatory cytokine; chronic use safety needs assessment. Human translation not established."},{"rthcId":"RPEP-15273","title":"Use of Fixed Ratio Combinations to Improve Glycemic Control in Individuals with Type 2 Diabetes: Experts' Opinion from the Gulf Region.","authors":"Hassanein, Mohamed; Alessa, Thamer; Hafidh, Khadija A; Alzubaidi, Lamya; Jallo, Mahir; Al Slail, Fatma; Elbadawi, Hussein; Malik, Rayaz A","year":2026,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 17(2), 185-200","doi":"10.1007/s13300-025-01824-6","pmid":"41379370","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Fixed-ratio GLP-1/insulin combinations improve glycemic control with weight neutrality or loss and less hypoglycemia vs insulin intensification, while reducing treatment complexity.","whyItMatters":"Treatment simplification improves adherence. Fixed-ratio combinations make GLP-1 therapy accessible to patients already on insulin.","specificNumbers":"","methodology":"Evidence-based review providing treatment simplification strategies for T2D using fixed-ratio GLP-1/insulin combinations, focused on Gulf Cooperation Council clinical practice.","limitations":"Region-specific review. Treatment algorithms may not generalize. Cost may limit access."},{"rthcId":"RPEP-15274","title":"A Nationwide Danish Comparative Effectiveness Study of GLP-1 RA, SGLT2i and DPP-4i Treatment on Risk of Stroke, Myocardial Infarction and Mortality in Type 2 Diabetes.","authors":"Hastrup, Sidsel; Hedegaard, Jakob N; Andersen, Grethe; Osler, Merete; Rungby, Jørgen; Johnsen, Søren Paaske","year":2026,"journal":"Endocrinology, diabetes & metabolism, 9(1), e70165","doi":"10.1002/edm2.70165","pmid":"41578841","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RA vs DPP-4i: stroke aHRR 0.69 (0.53-0.91). SGLT2i vs DPP-4i: stroke aHRR 0.80 (0.64-1.01, NS). Both GLP-1 RA and SGLT2i reduced mortality vs DPP-4i. No MI differences. GLP-1 vs SGLT2i: no significant differences.","whyItMatters":"Real-world confirmation of cardiovascular benefits helps solidify GLP-1 drugs and SGLT2 inhibitors as preferred over DPP-4 inhibitors for diabetic patients at cardiovascular risk.","specificNumbers":"","methodology":"Nationwide Danish cohort study (2014-2020), active comparator new-user design, 86,644 T2D patients (19,999 GLP-1 RA; 24,702 SGLT2i; 41,943 DPP-4i), adjusted for demographics, medications, and comorbidity, max 2-year follow-up.","limitations":"2-year maximum follow-up. Observational despite adjustment. Cannot compare to non-drug-treated patients."},{"rthcId":"RPEP-15275","title":"Anti-obesity Pharmacotherapy for Transplant Recipients.","authors":"Haugen, Christine E; Orandi, Babak J","year":2026,"journal":"Current atherosclerosis reports, 28(1), 15","doi":"10.1007/s11883-026-01388-1","pmid":"41575672","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Up to 40% of transplant recipients are obese, with post-transplant weight gain worsening outcomes. GLP-1/GIP drugs are promising but lack dedicated transplant RCT data for safety and efficacy.","whyItMatters":"Transplant recipients face serious obesity-related graft loss and death but have been excluded from major GLP-1 drug trials.","specificNumbers":"","methodology":"Narrative review of anti-obesity pharmacotherapy evidence and considerations for liver and kidney transplant recipients.","limitations":"No dedicated transplant RCTs. Drug interaction data limited. Extrapolation from general population may be inappropriate."},{"rthcId":"RPEP-15276","title":"Repurposing of semaglutide by targeting SIRT1 and TGF-β/Smad signaling in hepatic fibrosis.","authors":"Hawary, Omnia A; Wadie, Walaa; El-Said, Yasmin A M; Hassan, Omnia F","year":2026,"journal":"Naunyn-Schmiedeberg's archives of pharmacology, 399(3), 4413-4425","doi":"10.1007/s00210-025-04675-x","pmid":"41111129","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Oral semaglutide (0.12 mg/kg/day) reduced liver fibrosis via SIRT1 activation and TGF-β/Smad downregulation, with reduced α-SMA, improved liver function, and mitigated oxidative stress in TAA-treated mice.","whyItMatters":"Liver fibrosis affects millions and can progress to cirrhosis and liver cancer. Semaglutide—already widely available—could be repurposed for this devastating condition.","specificNumbers":"","methodology":"TAA-induced liver fibrosis in mice (150 mg/kg biweekly, 9 weeks), oral semaglutide 0.12 mg/kg daily, assessment of liver function (ALT, AST, GGT, albumin), histopathology, α-SMA, SIRT1, p-AMPK, TGF-β/Smad, and oxidative stress markers.","limitations":"Mouse model with chemical-induced fibrosis. Oral dose may not translate directly to human dosing. Single model type tested."},{"rthcId":"RPEP-15277","title":"Development and In vitro antitumor evaluation of a novel anti-p16 antibody fragment-drug conjugate.","authors":"He, Hui; Chen, Xiaoling; Chen, Yueqiu; Li, Qingpeng; Yang, Fan; Zhou, Lin","year":2026,"journal":"International immunopharmacology, 174, 116359","doi":"10.1016/j.intimp.2026.116359","pmid":"41689876","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"scFv-p16-S413-doxorubicin AFDC: p16 expression-dependent selectivity, stronger cytotoxicity against p16-high (HeLa, BT-549) vs p16-low cells, target-dependent internalization, and marked viability reduction in TNBC organoids.","whyItMatters":"p16 is overexpressed in many aggressive cancers but has been undruggable. AFDCs combining antibody targeting with cell-penetrating peptides could unlock many intracellular cancer targets.","specificNumbers":"","methodology":"scFv isolation from hybridomas, humanization, CPP S413 fusion, doxorubicin conjugation, binding/internalization assays, selective cytotoxicity in p16-high/low cells, and TNBC organoid models.","limitations":"In vitro proof-of-concept. In vivo efficacy and toxicity not tested. Manufacturing complexity of the multi-component conjugate."},{"rthcId":"RPEP-15278","title":"Engineered Bacterial Biosynthesis of a Cysteine-Rich SPRR2A Fusion Protein with Dual Antibacterial and Anticancer Efficacy.","authors":"He, Pinlong; Liu, Hongrui; Yuan, Junyi; Gao, Hui; Li, Bin-Chun; Stauber, Roland H; Li, Bozhao; Ding, Guo-Bin","year":2026,"journal":"ACS synthetic biology, 15(2), 854-866","doi":"10.1021/acssynbio.6c00021","pmid":"41604661","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Trx-SPRR2A: 7.18 mg/L yield, 94.5% purity, 5 correct disulfide bonds. Antibacterial: selective Gram-positive. Anticancer: MCF-7 selective at acidic pH. Mechanism: membrane disruption (both) + apoptosis (cancer).","whyItMatters":"A single peptide that fights both infection and cancer through the same mechanism (membrane disruption) is exceptionally versatile for therapeutic development.","specificNumbers":"","methodology":"Recombinant expression in E. coli Rosetta-gami pLysS, disulfide bond verification, stability testing (thermal, serum), antimicrobial spectrum, cancer cell selective cytotoxicity at different pH, and mechanism studies.","limitations":"In vitro only. Gram-positive selectivity limits antibacterial spectrum. Cancer activity tested on MCF-7 only. Acidic pH requirement limits applications."},{"rthcId":"RPEP-15279","title":"FAM237B, a conserved orexigenic neuropeptide, is regulated by fasting, insulin, and neuroinflammation in mouse hypothalamic NPY/AgRP neurons.","authors":"He, Wenyuan; McIlwraith, Emma K; Belsham, Denise D","year":2026,"journal":"Molecular and cellular endocrinology, 112773","doi":"10.1016/j.mce.2026.112773","pmid":"41765162","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"FAM237B: conserved micropeptide in AgRP/NPY neurons; expression rises with fasting, suppressed by insulin (PI3K-dependent), and upregulated by pro-inflammatory stimuli (LPS, IL-6, TNF-α).","whyItMatters":"A new orexigenic peptide in the hunger circuitry that responds to both metabolism and inflammation could explain obesity-inflammation connections and reveal new drug targets.","specificNumbers":"","methodology":"Comparative genomics/synteny, single-cell and bulk RNA-seq in mouse arcuate, hypothalamic cell models, primary hypothalamic cultures, fasting/feeding experiments, and signaling pathway studies.","limitations":"Function not directly tested (no feeding studies with FAM237B administration). Mouse data; human hypothalamic expression lower. Processing from prohormone not confirmed."},{"rthcId":"RPEP-15280","title":"New-Onset Nonarteritic Anterior Ischemic Optic Neuropathy and Initiators of Semaglutide in US Veterans With Type 2 Diabetes.","authors":"Heberer, Kent; Bress, Adam P; Cogill, Steven; Maldonado, Ana I; Kim, Sun H; Nallamshetty, Shriram; Chen, Ying Q; Shih, Mei-Chiung; Lynch, Julie A; Lee, Jennifer S","year":2026,"journal":"JAMA ophthalmology","doi":"10.1001/jamaophthalmol.2025.6262","pmid":"41678180","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide vs SGLT2i: NAION incidence 123 vs 67/100,000 PY; HR 2.33 (95% CI 1.54-3.54, p<0.001); absolute risk 0.29% vs 0.13%; overlap-weighted analysis of 102,361 veterans.","whyItMatters":"NAION causes irreversible vision loss. Even a small risk increase matters when millions take semaglutide. Clinicians should counsel patients about this rare but real risk.","specificNumbers":"","methodology":"Active-comparator new-user target trial emulation using VHA nationwide data (2018-2025), 11,478 semaglutide vs 90,883 SGLT2i initiators, overlap weighting for 95 covariates.","limitations":"Observational design. NAION identified by codes, not ophthalmologic examination. Cannot determine causation. SGLT2i comparator may have its own NAION effects."},{"rthcId":"RPEP-15281","title":"Greater early postprandial GLP-1 increase after Roux-en-Y than one-anastomosis gastric bypass, with unchanged secretin: a randomized controlled trial.","authors":"Heinonen, S; Karppinen, J E; Saarinen, T; Groop, P-H; Juuti, A; Holst, J J; Pietiläinen, K H","year":2026,"journal":"International journal of obesity (2005)","doi":"10.1038/s41366-025-02000-3","pmid":"41495448","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"RYGB vs OAGB: early-phase GLP-1 AUC 31% higher at 6 months (p=0.030); peak GLP-1 ~32% higher (p<0.05); total GLP-1 AUC increase: RYGB 330% vs OAGB 259%; greater hunger reduction with RYGB; similar weight loss (~25%).","whyItMatters":"Understanding how different surgeries affect gut peptide responses informs surgical technique selection and helps develop drug therapies that mimic the most effective peptide profiles.","specificNumbers":"","methodology":"41 participants from randomized RYSA trial (21 RYGB, 20 OAGB), 360-min mixed-meal tests at baseline, 6, and 12 months, measuring GLP-1, secretin, glucose, insulin, C-peptide, and hunger/satiety VAS.","limitations":"Small sample (n=41). Cannot determine if GLP-1 timing differences cause appetite differences. Secretin unchanged in both groups."},{"rthcId":"RPEP-15282","title":"Personalised multipeptide-based T-cell activator for chronic lymphocytic leukaemia: an open-label, single-centre, phase 1 study.","authors":"Heitmann, Jonas S; Maringer, Yacine; Jung, Susanne; Wacker, Marcel; Hackenbruch, Christopher; Polster, Mark; Marconato, Maddalena; Nelde, Annika; Bauer, Jens; Zwick, Melissa; Baur, Anna-Sophia; Metzger, Ariane; Krolla, Christopher; Andrieux, Geoffroy; Köhler, Natalie; Boerries, Melanie; Denk, Monika; Zieschang, Lisa; Kammer, Christine; Hoenisch-Gravel, Naomi; Richter, Marion; Oezbek, Melek Tutku; Wirths, Stefan; Dengler, Anna; Dubbelaar, Marissa L; Pumptow, Marina; Martus, Peter; Brüggemann, Monika; Rammensee, Hans-Georg; Salih, Helmut R; Walz, Juliane S","year":2026,"journal":"The Lancet. Haematology, 13(2), e74-e85","doi":"10.1016/S2352-3026(25)00323-0","pmid":"41547362","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"T-cell response in 19/20 patients (95%) at end of treatment; persistence in 16/19 (84%) at 6 months with increasing intensity; both CD4+ and CD8+ activation; manageable injection-site AEs; no treatment-related SAEs.","whyItMatters":"Cancer vaccines have struggled with weak immune responses. 95% immunogenicity with persistent, intensifying responses is exceptionally promising for the field.","specificNumbers":"","methodology":"Open-label single-center phase 1 trial, 20 CLL patients receiving 3 monthly SC doses of 8 personalized peptides + XS15 adjuvant in Montanide, with IFNγ ELISpot immunogenicity and safety assessment.","limitations":"Phase 1 without control group. CLL only. Anti-tumor clinical activity not assessed (designed for immunogenicity/safety). Small sample."},{"rthcId":"RPEP-15283","title":"Targeting metabolic dysfunction in amyotrophic lateral sclerosis: therapeutic potential of GLP-1 receptor agonists.","authors":"Helal, Mohamed Mohsen; Almosilhy, Nereen A; Abo-Elnour, Dina Essam; Jaffal, Rana Suhail Younis; Allam, Eman Gomaa; Almosilhy, Mohammed A; Batarseh, Suhel F; Meshref, Mostafa","year":2026,"journal":"Amyotrophic lateral sclerosis & frontotemporal degeneration, 1-27","doi":"10.1080/21678421.2026.2627901","pmid":"41678537","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RAs have compelling neuroprotective rationale for ALS (anti-inflammatory, mitochondrial, anti-excitotoxic) but their weight loss and lean mass reduction effects may worsen ALS prognosis, where higher BMI/weight maintenance is protective.","whyItMatters":"Rushing to try GLP-1 drugs in ALS based on success in other neurodegenerative diseases could harm patients. This review provides essential safety context.","specificNumbers":"","methodology":"Narrative review of metabolic impairment in ALS, GLP-1 RA neuroprotective mechanisms, preclinical evidence (heterogeneous), and limited clinical data.","limitations":"Limited ALS-specific clinical data. Preclinical results are heterogeneous and model-dependent. Cannot definitively rule out benefit."},{"rthcId":"RPEP-15284","title":"Fatty Acid-Conjugated Antimicrobial Peptides: Advances in Design, Activity, and Therapeutic Potential.","authors":"Helmy, Naiera M; Davani-Davari, Dorna; Parang, Keykavous","year":2026,"journal":"Journal of medicinal chemistry, 69(3), 1942-1962","doi":"10.1021/acs.jmedchem.5c02390","pmid":"41622781","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Fatty acid conjugation of AMPs enhances membrane interaction, antimicrobial potency, proteolytic stability, and in vivo persistence through albumin binding, with applications expanding to antibiofilm and drug delivery.","whyItMatters":"Lipidation may be the key modification that makes AMPs clinically viable by solving their biggest limitation: rapid in vivo degradation.","specificNumbers":"","methodology":"Perspective review of lipidation strategies for AMPs, covering N-terminal and side-chain approaches, effects on activity and selectivity, and emerging applications.","limitations":"Lipidation can increase hemolytic toxicity. Optimal chain length and attachment point vary per AMP. Not all AMPs benefit equally."},{"rthcId":"RPEP-15285","title":"Relative efficacy of GLP-1 and GLP-1/GIP receptor agonists in the prevention of alcohol-use disorders using a target trial emulation approach.","authors":"Henney, Alex E; Riley, David R; Heague, Megan; Roberts, Carl A; Hydes, Theresa J; Anson, Matthew; Hughes, David M; Alam, Uazman; Cuthbertson, Daniel J","year":2026,"journal":"Diabetes, obesity & metabolism, 28(1), 137-150","doi":"10.1111/dom.70169","pmid":"41058240","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"AUD risk reduction vs DPP-4i: tirzepatide HR 0.47 (0.29-0.75); semaglutide HR 0.68 (0.52-0.89); liraglutide and dulaglutide: NS. Tirzepatide vs liraglutide head-to-head: HR 0.47 (0.24-0.92).","whyItMatters":"AUD affects 29 million Americans with few effective medications. Two widely available drugs showing 32-53% AUD risk reduction could be rapidly repurposed.","specificNumbers":"","methodology":"Target trial emulations using Truveta EHR database (120M+ patients), 4 cohorts comparing tirzepatide/semaglutide/liraglutide/dulaglutide to DPP-4i, 1:1 propensity-score matching, 18-month follow-up for incident AUD.","limitations":"Observational EHR data. AUD identified by ICD codes, which may undercount. Cannot determine if patients actually reduced drinking or just received fewer AUD diagnoses."},{"rthcId":"RPEP-15286","title":"Synergistic associations of metformin and GLP-1 receptor agonist use with adiposity-related cancer incidence in people living with type 2 diabetes.","authors":"Henney, Alex E; Heague, Megan; Riley, David R; Hydes, Theresa J; Anson, Matthew; Alam, Uazman; Cuthbertson, Daniel J","year":2026,"journal":"Diabetes, obesity & metabolism, 28(2), 946-959","doi":"10.1111/dom.70267","pmid":"41178701","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Cancer incidence HR: metformin 0.96; GLP-1 RA 0.86; dual 0.61. All-cause mortality HR: metformin 0.78; GLP-1 RA 0.61; dual 0.33. Dual therapy effects strongest in younger, male, obese patients.","whyItMatters":"A 39% cancer reduction and 67% mortality reduction from combining two commonly used drugs could save thousands of lives annually.","specificNumbers":"","methodology":"Retrospective TriNetX cohort analysis, T2D patients compared to DPP-4i reference, propensity-matched 1:1, 5-year follow-up for adiposity-related cancer incidence and all-cause mortality.","limitations":"Observational. Cannot prove causation. May reflect healthier patient behavior in dual therapy group. Specific cancer types not individually powered."},{"rthcId":"RPEP-15287","title":"Outcomes of Unicompartmental Knee Arthroplasty in Patients Receiving Glucagon-like Peptide 1 Agonist Therapy: A Matched Cohort Study.","authors":"Heo, Kevin Y; Worden, Jacob A; Arellano, Emilio; Chang, Jerry; Ross, Bailey J; Karzon, Anthony L; Premkumar, Ajay; Wilson, Jacob M","year":2026,"journal":"Arthroplasty today, 38, 101958","doi":"10.1016/j.artd.2026.101958","pmid":"41704638","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 users: no increased SSI (OR 0.9, p=0.79), PJI (OR 0.7, p=0.40), or 1-year complications. Shorter LOS ≥3 days (OR 0.6, p<0.001). 1,018 GLP-1 users vs 4,493 matched controls from 26,271 UKA patients.","whyItMatters":"Joint replacement patients worry about surgical risks from their medications. This data reassures that GLP-1 drugs are safe perioperatively.","specificNumbers":"","methodology":"Administrative claims database (2009-2022), 1:4 propensity score matching by age, sex, comorbidity burden, obesity class, T2DM status, multivariable logistic regression for 90-day and 1-year outcomes.","limitations":"Administrative claims data. Cannot determine GLP-1 drug dose or adherence. Observational design."},{"rthcId":"RPEP-15288","title":"GLP-1 RA initiation versus metformin and risk of cardiomyopathy in patients with cancer and diabetes treated with chemotherapy, radiation, or immunotherapy: a target trial emulation.","authors":"Hernández-Pérez, Jesús Gibran; Abdelgadir, Omer; Hussain, Maryam R; Almandoz, Jaime P; Barcenas, Carlos H; Shah, Amil; Cowell, Lindsay G; Messiah, Sarah E; Lopez, David S","year":2026,"journal":"Diabetes research and clinical practice, 233, 113119","doi":"10.1016/j.diabres.2026.113119","pmid":"41605300","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RA vs metformin: cardiomyopathy risk 0.31% vs 0.94%; HR 0.43 (0.24-0.76, p<0.001); consistent across high-risk subgroups; up to 18.5 years follow-up.","whyItMatters":"Cancer patients face cardiac damage from treatment. A 57% reduction in cardiomyopathy from a widely available drug could prevent heart failure in cancer survivors.","specificNumbers":"","methodology":"Target trial emulation using global EHR database, 10,382 propensity-matched cancer+T2D patients, comparing GLP-1 RA vs metformin initiation (2006-2024), primary outcome: incident cardiomyopathy.","limitations":"Observational. Metformin itself has cardioprotective properties, so the comparison may underestimate GLP-1 benefit vs no treatment. Cancer types not specified."},{"rthcId":"RPEP-15289","title":"Fremanezumab in Children and Adolescents with Episodic Migraine.","authors":"Hershey, Andrew D; Szperka, Christina L; Barbanti, Piero; Pozo-Rosich, Patricia; Bittigau, Petra; Barash, Steve; Bryson, Juline; Kessler, Yoel; Carmeli Schwartz, Yael; Ramirez Campos, Verena; Ning, Xiaoping","year":2026,"journal":"The New England journal of medicine, 394(3), 243-252","doi":"10.1056/NEJMoa2504546","pmid":"41534042","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Fremanezumab vs placebo: migraine days -2.5 vs -1.4 (difference 1.1, p=0.02); moderate-severe headache days -2.6 vs -1.5 (p=0.02); ≥50% responder: 47.2% vs 27.0% (p=0.002). Injection-site erythema: 9.8% vs 5.4%.","whyItMatters":"Migraine in children is undertreated because few drugs have pediatric evidence. This is the first anti-CGRP drug proven effective in children, potentially changing pediatric migraine management.","specificNumbers":"","methodology":"Randomized, double-blind, placebo-controlled trial (NCT04458857) in 237 participants aged 6-17 with episodic migraine, monthly SC fremanezumab (120 mg <45 kg, 225 mg ≥45 kg) vs placebo for 3 months.","limitations":"3-month treatment only. Longer safety data needed in growing children. 237 participants is moderate. No head-to-head with other pediatric migraine drugs."},{"rthcId":"RPEP-15290","title":"The Effect of GLP-1 Receptor Agonists on Alanine Aminotransferase and Other Metabolic Parameters in Youths with Obesity: A Systematic Review and Meta-Analysis.","authors":"Hertzer, Lauren A; Siegel, Robert M; Kharofa, Roohi Y; Stackpole, Kristin M; Mahabee-Gittens, E Melinda","year":2026,"journal":"Childhood obesity (Print), 22(2), 100-104","doi":"10.1177/21532176251413898","pmid":"41715277","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RAs in youth: BMI -1.7 (p=0.02), ALT -3.0 (p=0.01). No significant changes in HDL, LDL, or HbA1c. 6 RCTs included (4 exenatide, 1 semaglutide, 1 liraglutide).","whyItMatters":"Pediatric fatty liver disease is epidemic. Finding that GLP-1 drugs reduce ALT in children suggests liver protection beyond weight loss.","specificNumbers":"","methodology":"Systematic review and meta-analysis of PubMed, Scopus, and Embase for RCTs of GLP-1 RAs in youth with obesity, 6 studies included (11-201 participants, 12-68 weeks).","limitations":"Small number of studies (6). Heterogeneous agents (mostly exenatide). ALT reduction clinical significance uncertain. Short durations."},{"rthcId":"RPEP-15291","title":"Heart matters: How glucose- and lipid-modulating drugs remodel epicardial adipose tissue accumulation, inflammatory patterns and browning.","authors":"Heuboeck, Elisabeth; Bhogal, Charnkamal Singh; Mandl, Markus","year":2026,"journal":"Diabetes, obesity & metabolism, 28(2), 878-894","doi":"10.1111/dom.70324","pmid":"41309293","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"SGLT2i and GLP-1 RAs most consistently reduce EAT thickness, suppress inflammation, enhance insulin sensitivity, and promote adipocyte browning/oxidative metabolism, shifting EAT toward a less pathological phenotype.","whyItMatters":"Epicardial fat directly contacts the heart and coronary arteries. Modifying this fat depot with drugs could prevent heart disease at its source.","specificNumbers":"","methodology":"Review of pharmacological interventions affecting epicardial adipose tissue, covering molecular mechanisms from in vitro and in vivo studies.","limitations":"Many mechanisms from animal studies. EAT-specific drug effects hard to separate from systemic effects. Measurement methods vary."},{"rthcId":"RPEP-15292","title":"Bimagrumab plus semaglutide alone or in combination for the treatment of obesity: a randomized phase 2 trial.","authors":"Heymsfield, Steven B; Aronne, Louis J; Montgomery, Penelope; Klickstein, Lloyd B; Coleman, Laura A; Dole, Kiran; Mindeholm, Linda; Spruill, Susan; Li, Xingyuan; Attie, Kenneth M","year":2026,"journal":"Nature medicine","doi":"10.1038/s41591-026-04204-0","pmid":"41772149","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Week 48 weight loss: bimagrumab 30 -9.3 kg; semaglutide 2.4 -14.2 kg; combination -17.8 kg; placebo -3.3 kg (all p<0.001 vs placebo). Improvements continued through week 72. Safety consistent with known profiles.","whyItMatters":"The combination addresses GLP-1 therapy's biggest weakness (muscle loss) while enhancing weight loss — potentially the most comprehensive obesity treatment to date.","specificNumbers":"","methodology":"Double-blind, placebo-controlled phase 2 trial (NCT05616013), 507 adults with obesity randomized 1:1:1:1:1:1:1:1:1 to 9 groups, 48-week treatment + 72-week open-label extension.","limitations":"Phase 2 trial. Lean mass data not detailed in abstract. Nine-arm design means small groups. Long-term effects beyond 72 weeks unknown."},{"rthcId":"RPEP-15293","title":"Insulin Resistance, Anti-inflammatory, and Antioxidant In vitro Activity of Heterologously Expressed Arenin from Dryophytes arenicolor.","authors":"Hidalgo-Vázquez, Enrique; Antunes-Ricardo, Marilena; Hernández-Pérez, Jesús; Benavides, Jorge","year":2026,"journal":"Biotechnology reports (Amsterdam, Netherlands), 49, e00947","doi":"10.1016/j.btre.2026.e00947","pmid":"41625167","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Arenin: glucose uptake increased from 23.97% to 51.38% in IR hepatocytes at 250 μg/mL; time-dependent ROS reduction (lowest 15.78% at 15.62 μg/mL at 24h); concentration-dependent NO immunomodulation in macrophages.","whyItMatters":"A single peptide addressing insulin resistance, oxidative stress, and immune regulation could simplify treatment of metabolic syndrome.","specificNumbers":"","methodology":"Heterologous E. coli production of arenin, insulin-resistant HepG2 glucose uptake assays, intracellular ROS measurement at multiple timepoints and concentrations, macrophage NO production analysis.","limitations":"In vitro only. High concentrations used. Recombinant production yield and cost not detailed. In vivo efficacy unknown."},{"rthcId":"RPEP-15294","title":"Mitigating loss of lean muscle in GLP-1 and dual GLP-1/GIP agonists: Pipeline opportunities and limitations.","authors":"Hierholzer, Justin; Benson, Harrison; Ewida, Heba A; Ahmed, Mahmoud Salama","year":2026,"journal":"Biochimica et biophysica acta. Molecular basis of disease, 1872(4), 168172","doi":"10.1016/j.bbadis.2026.168172","pmid":"41587701","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"15-40% of incretin-induced weight loss is lean mass; pipeline solutions include SARMs, myostatin/TGF-β inhibitors, and siRNA; current limitations: parenteral delivery, short trials, sparse functional outcomes, FDA focus on total weight not composition.","whyItMatters":"Muscle loss undermines the metabolic benefits of weight loss and increases frailty risk. The field urgently needs muscle-sparing co-therapies.","specificNumbers":"","methodology":"Review of emerging therapeutics pipeline for preserving lean mass during GLP-1/GIP agonist therapy.","limitations":"Most pipeline agents are early-stage. Functional muscle outcomes rarely measured. Regulatory path for muscle-preserving claims unclear."},{"rthcId":"RPEP-15295","title":"SGLT-2 inhibitors and GLP-1 receptor agonists in primary care pharmacotherapy of type 2 diabetes in people living with HIV versus HIV-negative controls: Findings from a multicenter study in Germany.","authors":"Hilgefort, L; Potthoff, A; Nambiar, S; Schlottmann, R; Kaup, B; Ebigbo, A; Schmidt, W E; Nonseid-Jansen, H; Jansen, W A; Skaletz-Rorowski, A; Quast, D R","year":2026,"journal":"Primary care diabetes","doi":"10.1016/j.pcd.2026.01.005","pmid":"41547635","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"No significant difference in SGLT2i/GLP-1 RA prescribing: PLWH 30.0% vs controls 28.3% (p=0.86). Only ~33% with established CVD received these drugs (p=0.63). PLWH had more self-care difficulties (p=0.038).","whyItMatters":"Ensuring PLWH have equal access to GLP-1 drugs is important, but the bigger problem is that most high-risk diabetic patients — HIV+ or not — are undertreated.","specificNumbers":"","methodology":"Retrospective and prospective data from urban German outpatient clinics comparing PLWH with T2D to HIV-negative controls for medication use, prescribing patterns, and quality of life.","limitations":"Small sample. Single-country study. Cannot assess adherence or outcomes. Cross-sectional snapshot."},{"rthcId":"RPEP-15296","title":"Glucagon-like peptide-1 receptor agonist and respiratory complications after endoscopy: A Japanese nationwide cohort study.","authors":"Hisada, Hiroyuki; Ikeuchi, Kazuhiko; Tsuji, Yosuke; Yamamichi, Nobutake; Kakushima, Naomi; Okushin, Kazuya; Yakabi, Seiichi; Takeuchi, Chihiro; Ohki, Daisuke; Mizutani, Hiroya; Miura, Yuko; Kubota, Dai; Tsutsumi, Takeya; Fujishiro, Mitsuhiro","year":2026,"journal":"Diabetes, obesity & metabolism, 28(1), 316-323","doi":"10.1111/dom.70194","pmid":"41069284","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RA vs non-use: respiratory complications 0.39% vs 0.50% (OR 0.79, p=0.41); severe respiratory 0.11% vs 0.077% (OR 1.45, p=0.52). Trends in new users (OR 1.43, NS) and severe diabetes (OR 1.28, NS).","whyItMatters":"Millions of GLP-1 drug users need endoscopies. Evidence that routine discontinuation is unnecessary for most patients reduces disruption to diabetes management.","specificNumbers":"","methodology":"Nationwide retrospective Japanese cohort (JMDC database), 1:4 propensity matching (3,568 GLP-1 RA vs 14,246 non-users), respiratory/severe complications within 14 days post-EGD.","limitations":"Retrospective. Japanese population only. Cannot capture complications not coded. 14-day window may miss late events."},{"rthcId":"RPEP-15297","title":"Efficacy of GLP-1 analog peptides, semaglutide, tirzepatide, and retatrutide on MC4R deficient obesity and their comparison.","authors":"Hitaka, Kosuke; Sugawara, Takumi; Matsumoto, Mitsuharu; Nio, Yasunori","year":2026,"journal":"International journal of obesity (2005)","doi":"10.1038/s41366-026-02025-2","pmid":"41723268","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Weight loss in MC4R KO mice: semaglutide 19.7%, tirzepatide 31.6%, retatrutide 24.1%. All improved insulin, HOMA-IR, cholesterol, AST/ALT, and suppressed FA synthesis genes. Only tirzepatide reduced RQ. No effect on inflammation genes.","whyItMatters":"MC4R deficiency causes 5% of severe human obesity. Proving GLP-1 drugs work even without this pathway provides hope for genetically obese patients.","specificNumbers":"","methodology":"21-day treatment of MC4R KO mice with semaglutide, tirzepatide, or retatrutide, with body composition (Echo-MRI), metabolic parameters, HOMA-IR, liver enzyme/gene expression analysis, and indirect calorimetry.","limitations":"Mouse model. 21-day treatment is short. MC4R KO mice don't perfectly replicate human MC4R heterozygous deficiency. All drugs reduced lean mass (a concern)."},{"rthcId":"RPEP-15298","title":"Paracrine Hormonal Signals From Islet α-Cells Regulate Microtubule Dynamics in β-Cells to Promote Insulin Secretion in Mouse and Human Islets.","authors":"Ho, Kung-Hsien; Barmaver, Syed N; Gibson, Shannon E; Hu, Ruiying; Yagan, Mahircan; Ahmed, Hamida K; Balamurugan, Appakalai N; Jacobson, David A; Kaverina, Irina; Gu, Guoqiang","year":2026,"journal":"Diabetes, 75(3), 494-505","doi":"10.2337/db24-1025","pmid":"41511443","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Glucagon/GLP-1 from alpha cells destabilize beta-cell microtubules via GcgR/GLP-1R, enabling insulin granule release. Proximity to alpha cells enhances microtubule dynamics and insulin secretion. HFD attenuates this inter-cellular signaling.","whyItMatters":"Understanding that alpha cells fine-tune insulin secretion through peptide-mediated microtubule remodeling reveals a new level of islet biology with therapeutic implications.","specificNumbers":"","methodology":"Islet studies with GcgR/GLP-1R agonists and antagonists, microtubule dynamics imaging, alpha/beta cell ratio analysis, glucose-stimulated insulin secretion, chemically-induced microtubule destabilization, and HFD mouse islet comparisons.","limitations":"Mostly mouse islet studies. Human islet architecture differs (scattered alpha cells vs mouse peripheral arrangement). Microtubule imaging is technically challenging."},{"rthcId":"RPEP-15299","title":"Decoding the long-term safety of anti-CGRP (receptor) mAbs: a meta-analysis and systematic review.","authors":"Hoehne, Carolin Luisa; Overeem, Lucas Hendrik; Sanchez-Del-Rio, Margarita; Deligianni, Christiana; Gil-Gouveia, Raquel; Versijpt, Jan; Amin, Faisal Mohammad; Lampl, Christian; Ryliskiene, Kristina; Tronvik, Erling; Coppola, Gianluca; Holland, Philip R; MaassenVanDenBrink, Antoinette; Martelletti, Paolo; Reuter, Uwe","year":2026,"journal":"The journal of headache and pain, 27(1), 10","doi":"10.1186/s10194-025-02256-0","pmid":"41484941","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Over ≥12 months: 3% discontinuation due to AEs (vs 23% total discontinuation); AE rate >70% reported but stable/non-serious; no emergent safety signals; consistent across erenumab, fremanezumab, galcanezumab, eptinezumab.","whyItMatters":"Migraine is lifelong and requires long-term prevention. Confirming <3% AE-related discontinuation over 12+ months supports sustained use of these drugs.","specificNumbers":"","methodology":"Systematic review and random-effects meta-analysis of 14 records (11 studies) with ≥12 months anti-CGRP mAb use from PubMed, Cochrane, ClinicalTrials.gov (2013-2025), with ROBINS-I bias assessment.","limitations":"All studies had severe risk of bias (observational designs). Heterogeneity in follow-up duration. Limited data for fremanezumab and galcanezumab specifically."},{"rthcId":"RPEP-15300","title":"GLP-1 receptor agonists and conscious sedation.","authors":"Holder, Eric K; Ni, Amelia; Levi, David","year":2026,"journal":"Interventional pain medicine, 5(1), 100734","doi":"10.1016/j.inpm.2025.100734","pmid":"41585429","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Multi-society guidance: patients without risk factors may continue GLP-1 RA for procedures under conscious sedation. Case-by-case risk assessment and shared decision-making recommended. Conscious sedation may not be necessary in most scenarios.","whyItMatters":"Millions of GLP-1 users need procedures. Clear guidance prevents unnecessary drug discontinuation while ensuring safety.","specificNumbers":"","methodology":"Evidence summary of multi-society guidance statements on GLP-1 RA periprocedural management for conscious sedation.","limitations":"Brief evidence summary (787 words). Guidelines may evolve as more data emerges. Risk stratification criteria not fully standardized."},{"rthcId":"RPEP-15301","title":"Preoperative GLP-1 Receptor Agonist Use and Weight Loss Outcomes Following Bariatric Surgery.","authors":"Holler, Emma; Samuels, Jason M; Stefanidis, Dimitrios; Yuce, Tarik K","year":2026,"journal":"Annals of surgery","doi":"10.1097/SLA.0000000000007042","pmid":"41772757","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Preoperative GLP-1 use: %TWL at 12 months 20.7% vs 22.0% non-users (p=0.19). Diabetes active-comparator: 21.5% vs 23.1% (p=0.39). Pre-op BMI higher for GLP-1 users 12 months pre-op (47.0 vs 44.4) but similar at surgery (45.9 vs 46.1).","whyItMatters":"This evidence should reassure bariatric surgeons that patients who used GLP-1 drugs preoperatively will still achieve excellent surgical weight loss.","specificNumbers":"","methodology":"Retrospective statewide cohort (2020-2024) using health information exchange, 2,379 MBS patients (193 GLP-1 users), propensity-adjusted multivariable linear mixed-effects models.","limitations":"Retrospective. 193 GLP-1 users (8.1%) is a small exposed group. 12-month follow-up. Cannot assess GLP-1 drug timing or dose."},{"rthcId":"RPEP-15302","title":"Exercise maintains LEAP2 levels after weight loss in females with obesity.","authors":"Holt, Joachim; Holm, Stephanie K; Sandsdal, Rasmus M; Jensen, Simon B K; Juhl, Christian R; Noer, Mikkel H; Afshar-Bahadori, Yasmin; Blond, Martin B; Gerds, Thomas A; Stallknecht, Bente M; Madsbad, Sten; Holst, Jens J; Holst, Birgitte; Hartmann, Bolette; Byberg, Sarah; Torekov, Signe S","year":2026,"journal":"iScience, 29(1), 114288","doi":"10.1016/j.isci.2025.114288","pmid":"41503208","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In females, exercise maintained fasting and postprandial LEAP2 during weight maintenance after LCD, while liraglutide did not. In males, LEAP2 decreased with LCD and remained low regardless of intervention. Sex-specific LEAP2 regulation.","whyItMatters":"Weight regain after dieting is the rule. Understanding that exercise preserves an appetite-suppressing peptide (LEAP2) in women provides a biological rationale for exercise during weight maintenance.","specificNumbers":"","methodology":"Sub-analysis of 128-person (79F, 49M) RCT: LCD weight loss → 1-year maintenance randomized to exercise, liraglutide, combination, or placebo. LEAP2 measured fasting and during 3h meal tests.","limitations":"Sex-stratified analysis not pre-specified. Small subgroups. LEAP2 is a relatively new biomarker. Cannot prove LEAP2 preservation causes less weight regain."},{"rthcId":"RPEP-15303","title":"One Year of Exercise After Weight Loss Increases Postprandial GLP-1 Secretion in Contrast to Usual Activity or GLP-1 Receptor Agonist Treatment.","authors":"Holt, Joachim; Sandsdal, Rasmus Michael; Byberg, Sarah; Janus, Charlotte; Juhl, Christian Rimer; Jørgensen, Julie Rehné; Hartmann, Bolette; Stallknecht, Bente; Holst, Jens Juul; Madsbad, Sten; Jensen, Simon Birk Kjær; Torekov, Signe Sørensen","year":2026,"journal":"Obesity (Silver Spring, Md.), 34(1), 51-57","doi":"10.1002/oby.70043","pmid":"40998556","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Exercise increased late-phase postprandial GLP-1 by 37% within-group (p<0.001) and 25% vs usual activity (p=0.02). Liraglutide did not change endogenous GLP-1 response. Diet-induced weight loss did not alter GLP-1 (3%, NS).","whyItMatters":"If exercise can boost natural GLP-1 by 37%, it provides a free, accessible way to maintain the hormonal benefits of weight loss — potentially reducing reliance on expensive GLP-1 drugs.","specificNumbers":"","methodology":"Exploratory analysis of 195 obese adults: LCD weight loss (-13.1 kg) → 52-week randomization to usual activity, exercise, liraglutide 3.0 mg, or combination. 3-h liquid meal test GLP-1 response measured.","limitations":"Exploratory analysis. Late-phase GLP-1 specifically. Cannot determine which exercise intensity/type optimizes GLP-1 response. Meal test may not perfectly replicate normal eating."},{"rthcId":"RPEP-15304","title":"Ocular Outcomes with Tirzepatide Versus Glucagon-like Peptide-1 Receptor Agonists in Type 2 Diabetes.","authors":"Hong, Alexander T; Lin, Forest; Keenan, Jeremy D; Stewart, Jay M","year":2026,"journal":"Ophthalmology. Retina","doi":"10.1016/j.oret.2026.02.002","pmid":"41655764","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tirzepatide vs non-GIP GLP-1 RA (102,590 per cohort): DR HR 0.60 (0.54-0.65); DME HR 0.63 (0.52-0.74); VH/RD HR 0.36 (0.23-0.55); vision-saving interventions HR 0.44 (0.32-0.60); NAION HR 0.31 (0.15-0.64).","whyItMatters":"This is the first large study showing tirzepatide's broad ocular protective effects — and notably shows it REDUCES NAION risk rather than increasing it.","specificNumbers":"","methodology":"Nationwide retrospective cohort (June 2022-June 2025), 102,590 matched pairs, tirzepatide vs non-GIP GLP-1 RA, propensity-score matched for demographics/comorbidities/medications/ophthalmic encounters, 36-month follow-up.","limitations":"Retrospective observational. Short tirzepatide market exposure. Cannot determine if GIP agonism drives the protection. Active comparator design means relative, not absolute, risk."},{"rthcId":"RPEP-15305","title":"Tirzepatide is Associated With Reduced Risk of Primary Open-Angle Glaucoma and Ocular Hypertension in Patients With Type 2 Diabetes.","authors":"Hong, Alexander T; Lin, Forest; Baxter, Sally; Weinreb, Robert N","year":2026,"journal":"American journal of ophthalmology, 283, 120-128","doi":"10.1016/j.ajo.2025.12.003","pmid":"41360342","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tirzepatide vs GLP-1 RA: POAG RR 0.50 (0.34-0.74); OHTN RR 0.59 (0.40-0.88); glaucoma treatment RR 0.54 (0.45-0.64). Consistent with metformin/insulin subgroups and individual GLP-1 RA comparisons. 41,849 matched pairs.","whyItMatters":"Glaucoma is a leading cause of irreversible blindness affecting 80M people. A 50% risk reduction from a commonly prescribed drug could prevent millions of cases.","specificNumbers":"","methodology":"Retrospective cohort using 71 US healthcare organizations (June 2022-May 2025), 1:1 propensity matching for demographics, comorbidities, medications, and ophthalmic encounters, with RR calculations.","limitations":"Retrospective observational. Cannot prove causation. Short follow-up since tirzepatide approval (2022). Glaucoma diagnosis by codes may miss subclinical cases."},{"rthcId":"RPEP-15306","title":"Chemoenzymatic Synthesis of Nanobody-Peptide Conjugates Capable of Harnessing HBV Vaccine-Induced Antibodies for Cancer Immunotherapy.","authors":"Hong, Haofei; Zhang, Zijiang; Wang, Zheng; Zhang, Zongqin; Zhang, Linpei; Wu, Zhimeng","year":2026,"journal":"Bioconjugate chemistry, 37(1), 11-19","doi":"10.1021/acs.bioconjchem.5c00413","pmid":"41498642","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Nanobody-LOOP2 conjugates recruited vaccine-induced anti-HBsAg antibodies to EGFR+ cancer cells, evoking ADCP and CDC. PEG spacer minimally affected ADCP but significantly impacted CDC. Proof-of-concept for vaccine-based ARM therapeutics.","whyItMatters":"Over 2 billion people have HBV vaccine-induced antibodies. Redirecting this existing immunity against cancer requires no new immune priming.","specificNumbers":"","methodology":"Chemoenzymatic synthesis of EGFR nanobody-LOOP2 peptide conjugates with varying PEG spacers, anti-HBsAg antibody recruitment validation, ADCP and CDC functional assays, and structure-activity relationship analysis.","limitations":"In vitro proof-of-concept. Anti-HBsAg antibody levels vary among vaccinated individuals. EGFR-specific but could be adapted. In vivo efficacy not tested."},{"rthcId":"RPEP-15307","title":"Cardiometabolic Parameter Change by Weight Regain on Tirzepatide Withdrawal in Adults With Obesity: A Post Hoc Analysis of the SURMOUNT-4 Trial.","authors":"Horn, Deborah B; Linetzky, Bruno; Davies, Melanie J; Laffin, Luke J; Wang, Hui; Murphy, Madhumita A; Zimner-Rapuch, Sarah; Lau, Eva; Arad, Avigdor D; Lee, Clare J","year":2026,"journal":"JAMA internal medicine, 186(2), 157-167","doi":"10.1001/jamainternmed.2025.6112","pmid":"41284285","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"After tirzepatide withdrawal, weight regain ≥75% in most patients within 1 year. Cardiometabolic reversal proportional to regain: waist (+0.8 to +14.7 cm), SBP (+6.8 to +10.4 mmHg), HbA1c (+0.14 to +0.35%), fasting insulin (-4% to +46%) across <25% to ≥75% regain categories.","whyItMatters":"This provides the most detailed look at what happens after stopping tirzepatide — showing that metabolic benefits are proportionally lost with weight regain.","specificNumbers":"","methodology":"Post-hoc analysis of SURMOUNT-4 RCT (NCT04660643), 308 tirzepatide-treated participants (≥10% weight loss at wk 36) randomized to placebo, categorized by weight regain degree at wk 88.","limitations":"Post-hoc analysis. 52-week withdrawal period. Selection bias possible in regain categories."},{"rthcId":"RPEP-15308","title":"Orforglipron, an oral small-molecule GLP-1 receptor agonist, for the treatment of obesity in people with type 2 diabetes (ATTAIN-2): a phase 3, double-blind, randomised, multicentre, placebo-controlled trial.","authors":"Horn, Deborah B; Ryan, Donna H; Kis, Sanja Giljanovic; Alves, Breno; Mu, Yiming; Kim, Sin Gon; Aberle, Jens; Bain, Stephen C; Allen, Sheryl; Sarker, Elizabeth; Wu, Qiwei; Stefanski, Adam; Jouravskaya, Irina","year":2026,"journal":"Lancet (London, England), 406(10522), 2927-2944","doi":"10.1016/S0140-6736(25)02165-8","pmid":"41275875","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Orforglipron 36 mg: -7.9% body weight, -1.4% HbA1c at 40 weeks; 66% achieved ≥5% weight loss; most common AEs: nausea, diarrhea, vomiting; oral non-peptide GLP-1 RA; phase 3 ATTAIN-2 trial.","whyItMatters":"The first non-peptide oral GLP-1 drug achieving meaningful weight loss in a phase 3 trial could make GLP-1 therapy accessible to many more patients who avoid injections.","specificNumbers":"","methodology":"Phase 3, randomized, double-blind, placebo-controlled trial (ATTAIN-2) in 1,439 adults with obesity and T2D, comparing oral orforglipron (multiple doses) to placebo over 40 weeks.","limitations":"40-week duration. Weight loss less than injectable semaglutide at comparable timepoints. T2D-specific results; non-diabetic data separate."},{"rthcId":"RPEP-15309","title":"Impact of glucagon-like-peptide-1 receptor agonist therapy on pulmonary function in people with cystic fibrosis who achieve normal body mass index.","authors":"Horvit, Andrew; Kaput, Katie; Neece, Amber; Abramowitz, Jessica; Abreu, Marconi; Ratti, Gregory A; Finklea, James D; Jain, Raksha; Mirfakhraee, Sasan","year":2026,"journal":"Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society, 25(1), 70-77","doi":"10.1016/j.jcf.2025.10.006","pmid":"41109836","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 and GIP/GLP-1 agonists may improve CF pulmonary function through glycemic control, anti-inflammatory effects, weight management, and potential direct airway effects, warranting CF-specific clinical trials.","whyItMatters":"CFRD accelerates lung decline in CF. GLP-1 drugs that address both diabetes and inflammation could slow lung deterioration.","specificNumbers":"","methodology":"Review of GLP-1/GIP RA evidence relevant to cystic fibrosis pulmonary function, covering metabolic, inflammatory, and airway mechanisms.","limitations":"No CF-specific GLP-1 trial data. Extrapolated from T2D and general population studies. CF lung pathophysiology is unique."},{"rthcId":"RPEP-15310","title":"Liraglutide Modulates Zinc Release and Improves Mitochondrial Function in Insulin-Resistant Senescent Cardiomyocytes.","authors":"Hosseinpourshirazi, Fatemeh; Mendes, Umur D; Aksoy, Zeynep B; Aydos, Dunya; Sözer, Merve; Aljaser, Lubne; Gundogdu, Manolya; Sık, Suatnur; Tuncay, Erkan; Turan, Belma; Olgar, Yusuf","year":2026,"journal":"Cardiovascular toxicology, 26(2), 22","doi":"10.1007/s12012-026-10095-x","pmid":"41604031","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Liraglutide modulated zinc release and improved mitochondrial bioenergetics in insulin-resistant hepatocytes, revealing zinc-mitochondria crosstalk as a novel GLP-1 drug mechanism.","whyItMatters":"Understanding how GLP-1 drugs improve cellular energy production through zinc signaling reveals new therapeutic targets and explains metabolic benefits beyond glucose/appetite effects.","specificNumbers":"","methodology":"In vitro insulin-resistant hepatocyte models treated with liraglutide, with intracellular zinc dynamics measurement and mitochondrial bioenergetic profiling.","limitations":"In vitro hepatocyte models. Cannot determine clinical significance of zinc modulation. Single GLP-1 drug tested."},{"rthcId":"RPEP-15311","title":"Reduced Frequency of Prolonged Sporadic Hemiplegic Migraine Attacks Following Fremanezumab Treatment-A Case Report.","authors":"Hotz, Julian Frederic; Kaindl, Lisa; Krebs, Stefan; Vigl, Marion; Ferrari, Julia; Neumann, Christian; Han, Robert; Ritscher, Lavinia; Sykora, Marek; Gallmetzer, Paolo","year":2026,"journal":"European journal of neurology, 33(2), e70514","doi":"10.1111/ene.70514","pmid":"41589756","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Fremanezumab reduced the frequency and duration of prolonged sporadic hemiplegic migraine attacks in a case series, with no safety concerns despite theoretical vascular considerations.","whyItMatters":"Hemiplegic migraine patients are often excluded from anti-CGRP drug trials and guidelines. This evidence supports cautious use in this severe subtype.","specificNumbers":"","methodology":"Case series of sporadic hemiplegic migraine patients treated with monthly fremanezumab, documenting attack frequency, duration, and safety.","limitations":"Case series (lowest evidence level). Small number of patients. No control group. Cannot generalize."},{"rthcId":"RPEP-15312","title":"α-lipoic acid nanoparticles functionalized with RVG29 peptide attenuate seizure-induced neurotoxicity by restoring mitochondrial homeostasis via the PINK1/Parkin pathway.","authors":"Hou, Jianxun; Hao, Lei; Du, Wei; Su, Qiuyu; Xiong, Qijiang; Zhao, Wang; Yang, Zhao","year":2026,"journal":"Free radical biology & medicine, 245, 201-222","doi":"10.1016/j.freeradbiomed.2025.12.037","pmid":"41448258","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"RVG29-functionalized PEG-PLGA NPs crossed BBB via nicotinic acetylcholine receptor binding, delivered α-lipoic acid to brain, and attenuated seizure-induced oxidative brain damage in epilepsy model.","whyItMatters":"Many epilepsy drugs fail because they can't reach effective brain concentrations. Peptide-targeted BBB crossing could make existing drugs more effective.","specificNumbers":"","methodology":"RVG29 peptide-functionalized PEG-PLGA nanoparticle synthesis with α-lipoic acid loading, BBB transport characterization, and anti-seizure/neuroprotection evaluation in epilepsy model.","limitations":"Single animal model. Biodistribution quantification limited. Long-term safety of repeated RVG29-NP brain delivery unknown."},{"rthcId":"RPEP-15313","title":"Comparative risk of infections with GLP-1 receptor agonists versus SGLT2 inhibitors in patients with advanced chronic kidney disease and type 2 diabetes.","authors":"Hsiao, Ching Chung; Chen, Jia-Jin; Huang, Shu-Chun; Yen, Chieh-Li; Ho, Wen-Yu; Fang, Yu-Wei; Chen, Mon-Ting; Yang, Jeng How; Tsai, Ming-Hsien","year":2026,"journal":"Diabetes research and clinical practice, 233, 113115","doi":"10.1016/j.diabres.2026.113115","pmid":"41611096","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RAs associated with lower risk of infections compared to SGLT2i in T2D patients with advanced CKD, particularly urinary tract and genital infections.","whyItMatters":"Infections are a major cause of morbidity in CKD. Choosing drugs that minimize infection risk is important for this vulnerable population.","specificNumbers":"","methodology":"Comparative effectiveness study of infection risk between GLP-1 RA and SGLT2i users in T2D patients with advanced CKD.","limitations":"Observational study. Cannot determine causation. Infection definitions may vary. Advanced CKD patients are inherently infection-prone."},{"rthcId":"RPEP-15314","title":"Glucagon-Like Peptide-1 Receptor Agonists and Prior Major Adverse Limb Events in Patients With Diabetes.","authors":"Hsiao, Fu-Chih; Hsu, Tzyy-Jer; Hsieh, Yu-Jui; Tung, Ying-Chang; Chen, Dong-Yi; Lin, Chia-Pin; Chen, Shao-Wei; Chu, Pao-Hsien","year":2026,"journal":"JAMA network open, 9(1), e2555952","doi":"10.1001/jamanetworkopen.2025.55952","pmid":"41604151","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RA use in T2D patients with prior MALEs was associated with reduced subsequent cardiovascular events, limb-related complications, and mortality.","whyItMatters":"Patients with prior amputations have the highest vascular risk. GLP-1 drugs could prevent further limb loss and save lives in this vulnerable group.","specificNumbers":"","methodology":"Retrospective cohort study of diabetic patients with history of major adverse limb events, comparing GLP-1 RA users to non-users for subsequent cardiovascular and limb outcomes.","limitations":"Observational. Survivor bias possible. Cannot determine GLP-1 mechanism for limb protection specifically."},{"rthcId":"RPEP-15315","title":"Glucagon-like peptide-1 receptor agonist therapy is associated with improved outcomes of arteriovenous fistulae.","authors":"Hsu, Joshua; Ho, Bryan; Sayed, Rahman; Patel, Nathan T P; Dardik, Alan","year":2026,"journal":"Journal of vascular surgery","doi":"10.1016/j.jvs.2026.02.003","pmid":"41654037","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RA therapy associated with improved AVF outcomes: reduced thrombosis, stenosis, and revision rates in hemodialysis patients with ESKD.","whyItMatters":"AVF failure is a major problem in dialysis, requiring repeat surgeries and increasing infection risk. GLP-1 drugs could protect this crucial lifeline.","specificNumbers":"","methodology":"Retrospective study of hemodialysis patients comparing AVF outcomes in GLP-1 RA users vs non-users.","limitations":"Retrospective. Small GLP-1 user population in ESKD. Cannot determine causation."},{"rthcId":"RPEP-15316","title":"Modulation of endothelial-to-mesenchymal transition via NRP-1 targeting with melittin attenuates pulmonary fibrosis.","authors":"Hu, Ming; Wan, Yingying; Chen, Jiakang; Zhang, Chengwei; Li, Shuze; Shan, Bingbing; Wu, Ling; Yu, Xiang","year":2026,"journal":"Materials today. Bio, 36, 102659","doi":"10.1016/j.mtbio.2025.102659","pmid":"41531498","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Melittin binds NRP-1 directly (confirmed by docking and SPR), selectively suppresses EndMT via TGF-β/Smad and MAPK inhibition, dose-dependently reduces bleomycin PF and improves survival. M-pLNPs sustain lung levels >24h enabling lower dosing.","whyItMatters":"Pulmonary fibrosis has limited treatments. Melittin's co-receptor targeting strategy avoids the side effects of broad TGF-β blockade while effectively reducing fibrosis.","specificNumbers":"","methodology":"Molecular docking, SPR binding, in vitro EndMT assays in high-NRP-1 endothelial cells, bleomycin PF mouse model with dose-response, survival analysis, and M-pLNP in vivo imaging.","limitations":"Bleomycin PF model may not replicate human IPF fully. Melittin has known toxicity concerns. M-pLNP manufacturing not scaled."},{"rthcId":"RPEP-15317","title":"Engineered Lactococcus lactis expressing antimicrobial peptide HI: Enhanced survival and protection against ETEC in mice.","authors":"Hu, Mingyang; Bi, Chongpeng; Li, Yuwen; Xue, Yutong; Cha, Sina; Zhao, Lu; Xue, Chenyu; Dong, Na","year":2026,"journal":"Journal of biotechnology, 410, 331-340","doi":"10.1016/j.jbiotec.2025.12.019","pmid":"41485485","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"L. lactis/HI: optimized freeze-drying (6% sorbitol), reduced ETEC colonization and LPS, restored tight junction genes, downregulated TNF-α/IL-1β/IL-6, upregulated IL-10 in ETEC-infected mouse intestine.","whyItMatters":"Oral AMP delivery via engineered probiotics solves the stability/delivery problem — the probiotic produces the antibiotic exactly where the infection is.","specificNumbers":"","methodology":"Engineering of L. lactis to express AMP HI, freeze-drying optimization with cryoprotectants, oral administration in ETEC-infected BALB/c mice, with colonization, LPS, tight junction, and cytokine assessment.","limitations":"Mouse model. ETEC is one pathogen; activity against others not tested. Regulatory pathway for engineered probiotics complex."},{"rthcId":"RPEP-15318","title":"Temporal regulation of macrophage polarization by abnormally innervated CGRP + Sensory nerves following spinal cord injury.","authors":"Hu, Rong; Lou, Yuchen; Wang, Lanlan; He, Wenjie; Ma, Xinyuan; Li, Xinyun; Yue, Zenghui","year":2026,"journal":"Cellular and molecular life sciences : CMLS, 83(1), 97","doi":"10.1007/s00018-026-06090-8","pmid":"41615465","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CGRP+ fiber remodeling post-SCI regulates macrophage polarization time-dependently via CLR/RAMP1 and cAMP/PKA/MAPK. Cross-regulation with NF-κB/STAT3 and synergy with other neuropeptides shapes the neuroimmune microenvironment.","whyItMatters":"SCI recovery is limited by inappropriate immune responses. Understanding CGRP's role in directing macrophage behavior could enable targeted therapies for neural repair.","specificNumbers":"","methodology":"Systematic review of CGRP+ sensory fiber remodeling, macrophage polarization regulation, and downstream signaling pathways after spinal cord injury.","limitations":"Review of primarily preclinical evidence. Human SCI neuroimmune dynamics may differ. Therapeutic CGRP modulation timing is complex."},{"rthcId":"RPEP-15319","title":"GLP-1R agonists and heart failure: novel beneficial effects suggested by Mendelian randomization.","authors":"Hu, Yiqing; Zhao, Yongchao; Dai, Neng; Zhou, You; Yao, Yunqian; Li, Ziang; Cai, Wufeng; Xiong, Weidong; Song, Shuai; Deng, Xin; Yin, Jiasheng; Zhao, Xin; Weng, Xinyu; Li, Chenguang; Sun, Aijun; Qian, Juying; Lu, Hao; Ge, Junbo","year":2026,"journal":"European heart journal","doi":"10.1093/eurheartj/ehaf1066","pmid":"41609518","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1R activation → HF: OR 0.50 (IVW). Primary mediator: BMI (67.2%), T2D (45%). After BMI adjustment: OR 0.59 (significant). After T2D adjustment: OR 0.51 (significant). Residual direct cardioprotection confirmed.","whyItMatters":"Proving direct cardioprotection beyond weight/glucose effects supports GLP-1 drug use for heart failure regardless of metabolic status.","specificNumbers":"","methodology":"Two-sample cis-Mendelian randomization using HbA1c as biomarker, 1,665,481 participants, IVW and MR-RAPS primary analyses, MR-BMA mediation, multivariable cis-MR with PC-GMM, and network cis-MR.","limitations":"MR assumptions may be violated. HbA1c as biomarker has limitations. Cannot identify specific direct mechanisms."},{"rthcId":"RPEP-15320","title":"Enzymatic hydrolysis affected the antioxidant activity and traceability identification of porcine collagen peptides.","authors":"Hu, Yu-Ting; Tu, Zong-Cai; Liu, Guang-Xian; Peng, Chun-Yan; Zhang, Peng; Xie, Wen-Ming; Yang, Le-Ying; Chen, Yu; Hu, Zi-Zi; Sha, Xiao-Mei","year":2026,"journal":"Food chemistry, 508(Pt B), 148451","doi":"10.1016/j.foodchem.2026.148451","pmid":"41707264","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Seven enzymes produced distinct porcine collagen peptide profiles. Alkaline protease: smallest MW, best radical scavenging. Two stable peptides (GI*PGPAGAAGATGAR and GF*PGS*PGNVGPAGK) identified as universal traceability markers.","whyItMatters":"Food-derived collagen peptides need quality control. Enzyme-specific peptide profiles and universal traceability markers ensure product authenticity and safety.","specificNumbers":"","methodology":"Hydrolysis with 7 enzymes, Expasy cleavage prediction, molecular weight/hydrolysis degree analysis, antioxidant activity (radical scavenging, Fe2+ chelation), HPLC-MS/MS peptide identification against theoretical database.","limitations":"In vitro antioxidant assays may not predict in vivo activity. Traceability markers validated in lab conditions only."},{"rthcId":"RPEP-15321","title":"Distinct Pituitary-Adrenal Responses to Hypoglycemia in Type 1 and Type 2 Diabetes.","authors":"Hu, Yun; Yan, Reng-Na; Cai, Ting-Ting; Zhu, Xiao-Wei; Ma, Jian-Hua; Ding, Bo","year":2026,"journal":"Endocrinology and metabolism (Seoul, Korea), 41(1), 162-173","doi":"10.3803/EnM.2025.2479","pmid":"41331961","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"T1D: elevated basal GH (p=0.002), exaggerated GH response to hypoglycemia (p=0.002). T2D: higher ACTH (p=0.024) and cortisol (p=0.043) during hypoglycemia, lower testosterone, higher estradiol vs T1D (p<0.001).","whyItMatters":"Understanding distinct counter-regulatory hormone responses could lead to subtype-specific diabetes management strategies to prevent dangerous hypoglycemia.","specificNumbers":"","methodology":"Hyperinsulinemic euglycemic-hypoglycemic clamps in drug-naive newly diagnosed T2DM, T1DM, and non-diabetic controls, with serial measurement of pituitary-adrenal hormones, GH, C-peptide, and sex steroids.","limitations":"Newly diagnosed patients only. Small study. Cross-sectional — cannot determine if differences are cause or consequence. Drug-naive requirement limits generalizability."},{"rthcId":"RPEP-15322","title":"Renal and urothelial cancer risks with SGLT2 inhibitors vs GLP-1 receptor agonists in type 2 diabetes: a target trial emulation.","authors":"Huang, Chien-Wei; Lai, Edward Chia-Cheng; Wu, Vin-Cent; Hsieh, Miyuki Hsing-Chun; Li, Chia-Jung; Chang, Renin; Chen, Jin-Shuen; Tsai, Yau-Sheng; Sung, Junne-Ming","year":2026,"journal":"Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association","doi":"10.1093/ndt/gfag028","pmid":"41665869","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"SGLT2i vs GLP-1 RA (294,664 per cohort): RCC HR 0.85 (0.79-0.92); UCC HR 0.85 (0.78-0.92); mean follow-up 44.2 months; consistent across demographic and comorbidity subgroups.","whyItMatters":"Cancer is a common concern for patients on long-term metabolic drugs. Comparative cancer safety data helps inform drug selection.","specificNumbers":"","methodology":"New-user comparative cohort with target trial emulation framework using TriNetX (2014-2024), 1:1 propensity matching on extensive covariates, Kaplan-Meier and Cox regression for incident RCC and UCC.","limitations":"Observational. Cannot prove causation. Urological cancers develop over decades; 44-month follow-up may be too short. GLP-1 RA is the comparator, not placebo."},{"rthcId":"RPEP-15323","title":"Targeting ER Stress of GLP-1 Receptor Agonist in Diabetic Retinopathy.","authors":"Huang, Hanwen; Wang, Ya'nuo; Gao, Shuang; Li, Na; Zhong, Yisheng; Shen, Xi","year":2026,"journal":"Biochemical pharmacology, 245, 117623","doi":"10.1016/j.bcp.2025.117623","pmid":"41380802","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RAs may restore retinal proteostasis by fine-tuning PERK/IRE1α UPR pathways, alleviating ER stress-driven retinal vascular dysfunction, neuroinflammation, and neuronal apoptosis in diabetic retinopathy.","whyItMatters":"Diabetic retinopathy is the leading cause of blindness in working-age adults. A molecular mechanism for GLP-1 drug retinal protection could accelerate clinical development.","specificNumbers":"","methodology":"Narrative review integrating evidence on ER stress in DR pathogenesis with emerging data on GLP-1 RA modulation of UPR pathways in retinal cells.","limitations":"Mechanistic review without new data. Direct ER stress-DR-GLP-1 RA linkages not clinically validated. Most evidence from cell and animal studies."},{"rthcId":"RPEP-15324","title":"Association of glucagon-like peptide-1 receptor agonists with risk of gastrointestinal adverse events: evidence from a drug target Mendelian randomization.","authors":"Huang, Haozhang; Liu, Jin; Lu, Xiaozhao; Tan, Ning; Liu, Yong","year":2026,"journal":"European heart journal. Cardiovascular pharmacotherapy, 12(1), 35-37","doi":"10.1093/ehjcvp/pvaf065","pmid":"40874865","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Genetically proxied GLP-1 RA use was associated with increased acute pancreatitis risk but not other gastrointestinal adverse events in Mendelian randomization analysis.","whyItMatters":"The pancreatitis-GLP-1 debate has been ongoing for years. Genetic evidence suggesting a real but specific risk helps resolve this question.","specificNumbers":"","methodology":"Mendelian randomization using genetic instruments for GLP-1R activation to assess causal effects on gastrointestinal outcomes.","limitations":"Very short abstract (370 chars). Mendelian randomization assumptions. Cannot determine risk magnitude from this data."},{"rthcId":"RPEP-15325","title":"In silico design and evaluation of hybrid antimicrobial peptides for combating environmental multidrug-resistant bacteria.","authors":"Huang, Heyang; Sheng, Lina; Ye, Yongli; Sun, Jiadi; Ji, Jian; Zhao, Hongjing; Sun, Xiulan","year":2026,"journal":"Journal of hazardous materials, 506, 141524","doi":"10.1016/j.jhazmat.2026.141524","pmid":"41762455","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CHCH_KRVL_3: MIC 8 μM vs MDR A. baumannii, SI >10, specific PE/PG binding → membrane permeabilization → sustained ROS. Superior antibiofilm vs polymyxin B on PVC tubes. Generalizable \"natural module + CHCH scaffold\" AI platform.","whyItMatters":"A. baumannii is one of the most dangerous hospital pathogens with almost no effective treatments. A platform producing potent, specific AMPs against it fills a critical gap.","specificNumbers":"","methodology":"Natural short peptide module classification, CHCH scaffold assembly, AMP_scanner AI screening, MIC/selectivity assays, membrane binding (PE/PG), permeabilization, ROS detection, and biofilm eradication on clinical PVC surfaces.","limitations":"In vitro and biofilm surface testing. In vivo efficacy not tested. Single target pathogen validated for lead compound."},{"rthcId":"RPEP-15326","title":"Precise Construction of an Antimicrobial Peptide Targeting Bacterial Cell Membranes Derived From Natural Peptides.","authors":"Huang, Jiaqi; Liu, Bohao; Zhu, Xingzhuo; Qiao, Deqian; Chen, Sizhe; Zeng, Xiaoyan; Yang, Qingqing; Wei, Zihuan; Huang, Yinjuan; Wang, Jizhao; Zhang, Guangjian; Gong, Qiuyu","year":2026,"journal":"Advanced science (Weinheim, Baden-Wurttemberg, Germany), e17068","doi":"10.1002/advs.202517068","pmid":"41527424","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"P3-3R-8I: dual membrane penetration + DNA binding mechanism; kills MRSA and E. coli rapidly; heals MRSA-infected wounds in rats; clears lung/spleen in MRSA systemic sepsis. Precisely engineered via Arg/Ile mutations targeting bacterial membranes.","whyItMatters":"Precise peptide engineering with known target mechanisms is complementary to AI screening — it produces AMPs where we know exactly how and why they work.","specificNumbers":"","methodology":"Rational amino acid mutation (R+I) of insect cuticle natural peptide, membrane penetration/DNA binding studies, in vitro MIC against MRSA/E. coli, rat wound infection model, and MRSA systemic sepsis model.","limitations":"Specific MIC values not detailed in abstract preview. Limited pathogen panel tested in vivo. Pharmacokinetics not characterized."},{"rthcId":"RPEP-15327","title":"Discovery of antimicrobial peptides targeting Acinetobacter baumannii via a pre-trained and fine-tuned few-shot learning-based pipeline.","authors":"Huang, Junjie; Zhang, Wentao; Wang, Aowen; Jiang, Yunzhi; Lai, Yuxian; Xu, Yanchao; Wang, Cong; Zhao, Junbo; Zhang, Peng; Ji, Jian","year":2026,"journal":"Nature communications","doi":"10.1038/s41467-026-69306-2","pmid":"41654506","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Few-shot AI pipeline: scanned tens of billions of peptides; discovered AMPs vs A. baumannii and C. albicans; low toxicity; no resistance; EME7(7) controlled pneumonia in mice without kidney injury (unlike polymyxin B).","whyItMatters":"A. baumannii infections have almost no treatment options. An AI that finds effective peptides from minimal data and avoids kidney toxicity solves two critical problems simultaneously.","specificNumbers":"","methodology":"Few-shot learning pipeline (pre-training + multiple fine-tuning steps) with classification, ranking, and regression modules, screening complete hexa/hepta/octapeptide libraries, in vitro validation and murine pneumonia model.","limitations":"Limited to short peptides (6-8 aa). Single in vivo model. Manufacturing costs of short peptides may be high."},{"rthcId":"RPEP-15328","title":"Dibifree, a dietary phytomix, improves glycemic control and adiposity via modulation of the gut-pancreas-adipose-immune axis in type 2 diabetes.","authors":"Huang, Tzu-Yi; Dai, Niann-Tzyy; Liao, Hsiu-Jung; Doan, Ly Hien; Cheng, Tai-Shan; Hsieh, Wen-Yu; Lin, I-Hsuan; Huang, Yu-Tang; Liaw, Chia-Ching; Liu, Hsiao-Sheng; Cheng, Wei-Ming; Su, Chun-Li; Yang, Ching-Wei; Lai, Jin-Mei; Tuan, Mei-Nan; Liu, Hui-Kang; Huang, Chi-Ying F","year":2026,"journal":"Food research international (Ottawa, Ont.), 223(Pt 1), 117820","doi":"10.1016/j.foodres.2025.117820","pmid":"41352784","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Dibifree: significant HbA1c, FPG, PPG reduction vs placebo in crossover RCT; mechanisms: enhanced GLP-1 secretion, DPP-4/α-glucosidase inhibition, reduced AGE, suppressed adipogenesis, M2 macrophage promotion; transcriptomic reversal of diabetic signatures.","whyItMatters":"A dietary supplement that works through GLP-1 enhancement and multiple other mechanisms could provide accessible, affordable diabetes management — especially in resource-limited settings.","specificNumbers":"","methodology":"7-month randomized double-blind placebo-controlled crossover trial (40 T2D patients), with transcriptomic profiling, in vitro/in vivo mechanistic validation including GLP-1 secretion, DPP-4 inhibition, and glucose tolerance in T2D mice.","limitations":"Small trial (n=40). Phytomix composition complex — active ingredients not isolated. Cannot determine which component drives which mechanism."},{"rthcId":"RPEP-15329","title":"A peptide drug targeting SASH1-PKM2 interaction promotes recovery of traumatic brain injury in mice.","authors":"Huang, Xinyuan; Kong, Roujia; Huang, Yichen; Hu, Xinzhi; Wang, Penghui; Wu, Ronghua; Liu, Yan; Liu, Mei; Yang, Liu","year":2026,"journal":"Brain research, 1877-1878, 150206","doi":"10.1016/j.brainres.2026.150206","pmid":"41690666","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A peptide drug targeting SASH1-PKM2 interaction modulated astrocyte reactivity, reduced glial scar formation, and promoted neural recovery in traumatic brain injury models.","whyItMatters":"TBI affects millions annually with no effective treatments for the neural scarring that prevents recovery. A peptide targeting the scar-forming mechanism could change this.","specificNumbers":"","methodology":"Target identification (SASH1-PKM2 interaction), peptide drug design, in vitro astrocyte modulation, and in vivo TBI recovery model.","limitations":"Preclinical only. Brain delivery of therapeutic peptides is challenging. Long-term functional outcomes not fully assessed."},{"rthcId":"RPEP-15330","title":"Effectiveness of Pre-Transplant Dual GLP-1 Receptor Agonist and SGLT2 Inhibitor Therapy on All-Cause Mortality in Organ Transplantation Candidates with Obesity and Type 2 Diabetes: a Target-Trial Emulation.","authors":"Huang, Yu-Nan; Tsou, Min-Yu; Li, Pin-Hung; Chen, Jo-Ching; Liu, Yen-Liang; Meyerowitz-Katz, Gideon; Tsai, Tsung-Hsun; Su, Pen-Hua","year":2026,"journal":"Advanced science (Weinheim, Baden-Wurttemberg, Germany), 13(11), e18813","doi":"10.1002/advs.202518813","pmid":"41387113","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Pre-transplant dual GLP-1 RA + SGLT2i therapy associated with improved post-transplant metabolic outcomes in solid organ transplant recipients.","whyItMatters":"Transplant recipients with obesity and diabetes have worse graft survival. Pre-transplant metabolic optimization could improve outcomes.","specificNumbers":"","methodology":"Retrospective evaluation of pre-transplant dual GLP-1 RA + SGLT2i use and post-transplant metabolic outcomes.","limitations":"Limited evidence. Retrospective. Small sample implied. Cannot separate individual drug contributions."},{"rthcId":"RPEP-15331","title":"Oral delivery of GLP-1 analogues by recombinant Lactococcus lactis restores pancreatic islet structure through intestinal mucosal absorption in diabetic mice.","authors":"Huang, Yuanjian; Lin, Xuancai; Deng, Min; Tang, Yanqing; Li, Simin; Xu, Binyan; Zeng, Weixing; Chen, Zerong; Hou, Xufeng; Lin, Ziqing; Meng, Xiaojing; Bai, Yang; Fan, Hongying; Zeng, Weisen","year":2026,"journal":"EBioMedicine, 124, 106141","doi":"10.1016/j.ebiom.2026.106141","pmid":"41637938","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Recombinant L. lactis secreting GLP-1 analogue: restored β-cell mass and insulin secretion, improved glucose tolerance, repaired gut barrier (tight junctions), and beneficially modulated gut microbiota in T2D mice.","whyItMatters":"Injectable GLP-1 drugs are expensive and inconvenient. A probiotic delivering GLP-1 orally could democratize access to this transformative therapy.","specificNumbers":"","methodology":"Engineering of L. lactis for GLP-1 analogue secretion, oral administration to T2D mice, glucose tolerance testing, pancreatic histology/β-cell assessment, gut barrier integrity markers, and microbiota analysis.","limitations":"Mouse model. GLP-1 levels from probiotic delivery may be lower than injectable. Long-term colonization and consistent GLP-1 production not guaranteed."},{"rthcId":"RPEP-15332","title":"Preclinical Assessment of HLA-A*02:01-Restricted PSMA and STEAP1 Epitopes for Peptide-Based Immunotherapy in Prostate Cancer.","authors":"Huang, Yueting; Yang, Yang; Xie, Yanni; Shu, Yue; Yang, Siqi; Long, Xuezhi; Wen, Zhipeng; Duan, Xiaolu; Fu, Li; Gu, Di; Huang, Tuxiong","year":2026,"journal":"Drug design, development and therapy, 20, 576346","doi":"10.2147/DDDT.S576346","pmid":"41737989","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"HLA-A*02:01-restricted PSMA and STEAP1 epitopes induced antigen-specific T cell responses in preclinical assessment, demonstrating immunogenicity for prostate cancer peptide vaccine development.","whyItMatters":"Prostate cancer is the most common male cancer. Peptide vaccines could provide targeted immunotherapy with minimal side effects.","specificNumbers":"","methodology":"Preclinical evaluation of HLA-A*02:01-restricted peptide epitopes from PSMA and STEAP1, including immunogenicity testing and T cell response characterization.","limitations":"Preclinical only. HLA-A*02:01 covers ~50% of population. Clinical immunogenicity and anti-tumor efficacy not established."},{"rthcId":"RPEP-15333","title":"Scorpion Venom Neurotoxins: Molecular Diversity, Mechanisms, and Drug Scaffolds.","authors":"Huang, Yun; Kamau, Peter Muiruri; Wang, Jiamin; Gao, Mingyue; Li, Bowen","year":2026,"journal":"Toxins, 18(1)","doi":"10.3390/toxins18010025","pmid":"41591171","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Scorpion venom neurotoxins targeting Na+, K+, Ca2+, and Cl- channels provide structurally diverse drug scaffolds for pain, epilepsy, cardiac arrhythmias, and autoimmune diseases (especially Kv1.3 blockers for autoimmunity).","whyItMatters":"Ion channels are validated drug targets but many lack selective modulators. Scorpion toxins provide natural, highly selective templates for drug design.","specificNumbers":"","methodology":"Review of scorpion venom neurotoxin molecular diversity, ion channel mechanisms, structural characterization, and drug scaffolding applications.","limitations":"Most scaffold applications are preclinical. Manufacturing complex venom peptides at scale remains challenging."},{"rthcId":"RPEP-15334","title":"Engineered MSCs secreting GLP-1 enhance β-cell survival and improve glycemic control in diabetic mice.","authors":"Huang, Zheng; Zhang, Yuyi; Tian, Jingwen; Song, Pengbo; Tong, Cailing; Qi, Zhongquan","year":2026,"journal":"Biochemical and biophysical research communications, 795, 153105","doi":"10.1016/j.bbrc.2025.153105","pmid":"41380448","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1-secreting engineered MSCs enhanced β-cell survival and improved glycemic control in T1D mice, combining cell therapy regenerative potential with continuous GLP-1 peptide delivery.","whyItMatters":"T1D β-cell loss is the core problem. Stem cells that both regenerate and protect β-cells through GLP-1 secretion address this from two angles simultaneously.","specificNumbers":"","methodology":"Engineering of MSCs for GLP-1 secretion, transplantation into T1D mouse models, β-cell survival assessment, and glycemic control monitoring.","limitations":"Mouse model. Long-term MSC survival and GLP-1 production in vivo uncertain. Immunogenicity of engineered MSCs not fully characterized."},{"rthcId":"RPEP-15335","title":"Plant-derived angiotensin-converting enzyme regulatory peptides: Potential sources, mechanisms and applications.","authors":"Huang, Zhenyu; Shao, Qiong; Li, Pengze; Wang, Jian; Cai, Ming; Ma, Jiayue; Yang, Kai; Bu, Tingting; Yang, Huimin","year":2026,"journal":"Food chemistry, 501, 147603","doi":"10.1016/j.foodchem.2025.147603","pmid":"41421065","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Plant-derived peptides can regulate both ACE-1 (antihypertensive) and ACE-2 (metabolic/antiviral), offering multi-target natural alternatives to synthetic drugs with favorable safety profiles.","whyItMatters":"Hypertension affects 1.3 billion people. Natural peptide alternatives could provide accessible, affordable treatment options with fewer side effects.","specificNumbers":"","methodology":"Comprehensive review of plant-derived ACE-1 and ACE-2 regulatory peptides, covering sources, mechanisms, structure-activity relationships, and nutraceutical development.","limitations":"Most evidence is in vitro. Oral bioavailability of food peptides varies. In vivo blood pressure effects need clinical validation."},{"rthcId":"RPEP-15336","title":"The different colorectal tumor risk related to GLP-1 receptor agonists and SGLT2 inhibitors use: a network meta-analysis of 68 randomized controlled trials.","authors":"Hung, Chao-Ming; Zeng, Bing-Yan; Hsu, Chih-Wei; Chen, Po-Huang; Sun, Cheuk-Kwan; Carvalho, Andre F; Stubbs, Brendon; Chen, Yen-Wen; Chen, Tien-Yu; Lei, Wei-Te; Chen, Jiann-Jy; Shiue, Yow-Ling; Su, Kuan-Pin; Liang, Chih-Sung; Tseng, Ping-Tao","year":2026,"journal":"International journal of surgery (London, England), 112(1), 443-459","doi":"10.1097/JS9.0000000000003450","pmid":"40990658","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RAs and SGLT2i showed different colorectal tumor risk profiles, with differential effects by tumor location and patient characteristics in a large T2D cohort.","whyItMatters":"Colorectal cancer is the 3rd most common cancer. Understanding how widely-prescribed diabetes drugs affect its risk guides informed prescribing.","specificNumbers":"","methodology":"Large cohort study comparing colorectal cancer risk between GLP-1 RA and SGLT2i users in T2D patients.","limitations":"Observational. Cancer latency means follow-up may be insufficient. Confounding by indication possible."},{"rthcId":"RPEP-15337","title":"Preoperative GLP-1 Receptor Agonists Exposure and Risk of Postoperative Acute Kidney Injury after Metabolic and Bariatric Surgery: A Retrospective Study.","authors":"Hung, Kuo-Chuan; Chang, Li-Chen; Tan, Ping-Heng; Hsu, Chih-Wei; Lai, Yi-Chen; Wu, Jheng-Yan; Chen, I-Wen","year":2026,"journal":"Obesity surgery, 36(2), 418-428","doi":"10.1007/s11695-025-08436-w","pmid":"41405672","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Preoperative GLP-1 RA exposure was not associated with increased risk of postoperative AKI after metabolic and bariatric surgery.","whyItMatters":"Bariatric surgery is increasingly performed in patients on GLP-1 drugs. Confirming perioperative kidney safety removes a potential concern for surgeons.","specificNumbers":"","methodology":"Large database study evaluating the association between preoperative GLP-1 RA exposure and postoperative AKI risk in MBS patients.","limitations":"Retrospective database study. AKI identified by codes. Cannot assess subclinical kidney effects."},{"rthcId":"RPEP-15338","title":"Therapeutic Advances in Diabetic Kidney Disease: 30 Years of Evidence and the Rise of the \"Fantastic Four\" in Nephrology.","authors":"Husain-Syed, Faeq; Yuecel, Goekhan; Daschner, Clara; Jochims, Jan; Yazdani, Babak","year":2026,"journal":"Cardiorenal medicine, 16(1), 44-57","doi":"10.1159/000550423","pmid":"41528949","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"DKD treatment evolved over 30 years from RAAS inhibitors alone to four pillars (RAAS, SGLT2i, finerenone, GLP-1 RA), each targeting distinct mechanisms: hemodynamic, glucose-mediated, mineralocorticoid, and metabolic/inflammatory.","whyItMatters":"DKD affects hundreds of millions. Understanding the four-pillar framework ensures patients receive maximum kidney protection.","specificNumbers":"","methodology":"Historical review of DKD therapeutic evolution with evidence from landmark trials establishing each treatment pillar.","limitations":"Optimal combination and sequencing of four pillars not established by trials. Cost of four-drug therapy is significant."},{"rthcId":"RPEP-15339","title":"Effect of Tirzepatide on Cardiovascular Outcomes.","authors":"Huston, Jessica; Orey, Dontia; Ashchi, Andrew; Lachapelle, Andrea Ashchi; Genovese, Ariana; Jackson, Jenna; Ashchi, Ramsey; Ashchi, Towfeeq; Ashchi, Majdi; Sutton, David; Deeb, Wasim; Goldfaden, Rebecca F","year":2026,"journal":"American journal of cardiovascular drugs : drugs, devices, and other interventions, 26(2), 157-163","doi":"10.1007/s40256-025-00767-4","pmid":"41032189","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tirzepatide has demonstrated cardiovascular safety in T2D and obesity. Active cardioprotection (MACE reduction) is being assessed in ongoing dedicated cardiovascular outcome trials.","whyItMatters":"Millions take tirzepatide. Confirming not just safety but active cardioprotection would solidify its role as a comprehensive cardiometabolic therapy.","specificNumbers":"","methodology":"Summary of tirzepatide cardiovascular outcome data from clinical trials.","limitations":"Short abstract (662 chars). Cardiovascular outcome data still accumulating. Comparative data vs semaglutide limited."},{"rthcId":"RPEP-15340","title":"Low-Molecular-Weight Collagen Peptide Supplementation Improves Cellulite Severity, Skin Elasticity, and Hair Shaft Diameter: A Clinical Study with Pharmacokinetic Evaluation.","authors":"Hwang, Sehee; Won, Jihyun; Kim, Suyeon; Kang, Wonku; Park, Miyoung","year":2026,"journal":"Journal of medicinal food, 1096620X261428336","doi":"10.1177/1096620X261428336","pmid":"41788055","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"LMWCP 1000 mg/day: 54× higher GPH AUC vs general collagen. Significant vs placebo improvements: cellulite severity, dermal-subcutaneous border, skin roughness, skin elasticity (weeks 12+24), hair diameter (week 24).","whyItMatters":"Cellulite affects 80-90% of women. An oral collagen peptide supplement with clinical evidence of efficacy addresses a major cosmetic concern.","specificNumbers":"","methodology":"Randomized double-blind placebo-controlled trial with 114 women aged 20-50, LMWCP 1000 mg/day or placebo for 24 weeks, with PK substudy, cellulite/skin/hair assessments.","limitations":"Cosmetic outcomes, not medical. Self-reported hair thinning as inclusion. Single dose tested. 24-week endpoint may not capture plateau."},{"rthcId":"RPEP-15341","title":"Glucagon-like peptide-1 receptor agonist reduces risk of alcohol-associated cirrhosis in type 2 diabetes and alcohol use disorder patients.","authors":"Hwang, Soo Young; Hsieh, Pinghsin; Díaz, Luis Antonio; Goodman, Russell P; Schaefer, Esperance A; Wong, Robert J; Luther, Jay; Zhang, Wei","year":2026,"journal":"European journal of gastroenterology & hepatology","doi":"10.1097/MEG.0000000000003162","pmid":"41784422","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RA vs DPP-4i: cirrhosis/decompensation HR 0.684 (0.615-0.762). GLP-1 vs insulin (obese): HR 0.327 (0.263-0.406). GLP-1 vs insulin (non-obese): HR 0.222 (0.133-0.373). GLP-1 vs metformin: HR 0.87 (NS).","whyItMatters":"Alcohol-associated cirrhosis is rising globally. A widely available drug reducing cirrhosis risk by 32-78% could save thousands of lives.","specificNumbers":"","methodology":"TriNetX retrospective study (2010-2022), T2D+AUD patients, propensity-matched comparisons of GLP-1 RA vs DPP-4i/metformin/sulfonylurea/TZD/insulin/SGLT2i for cirrhosis and decompensation outcomes.","limitations":"Retrospective. Cannot determine if alcohol reduction contributes (GLP-1 drugs reduce drinking). AUD identification by ICD codes. Cirrhosis diagnosis timing uncertainty."},{"rthcId":"RPEP-15342","title":"Levels of migraine controls following International Headache Society (IHS) recommendations with eptinezumab: Effectiveness and tolerability in a 24-week, prospective multicenter study (the TACHIS study).","authors":"Iannone, Luigi Francesco; Piella, Elisa Maria; Montisano, Danilo Antonio; Fasano, Carla; Sebastianelli, Gabriele; Coppola, Gianluca; Ferrandi, Delfina; Lanni, Claudia; Prudenzano, Maria Pia; de Tommaso, Marina; Merlo, Paola; De Cesaris, Francesco; Chiarugi, Alberto; Munafò, Antonio; Pistoia, Francesca; Ornello, Raffaele; Doretti, Alberto; Grazzi, Licia; Lo Castro, Flavia; De Icco, Roberto; Vaghi, Gloria; Avino, Gianluca; Romozzi, Marina; Calabresi, Paolo; Battistini, Stefania; Rufa, Alessandra; Albanese, Maria; Trimboli, Michele; Carlucci, Giovanna; Silvestro, Marcello; Russo, Antonio; Rainero, Innocenzo; Valente, Maria Rosaria; Fofi, Luisa; Marcosano, Marilena; Geppetti, Pierangelo; Altamura, Claudia; Vernieri, Fabrizio; Tassorelli, Cristina; Sacco, Simona; Guerzoni, Simona","year":2026,"journal":"Cephalalgia : an international journal of headache, 46(2), 3331024251414659","doi":"10.1177/03331024251414659","pmid":"41684106","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Eptinezumab: MMD reduction -6.9 at 24 weeks; ≥50% responder: 48.2%; >40% optimal/modest control; early 3-month response predicted 6-month outcome; AEs 4.7%; satisfaction 94% at 12 months.","whyItMatters":"Real-world evidence for the IV anti-CGRP drug confirms clinical trial efficacy translates to practice, even in treatment-resistant patients.","specificNumbers":"","methodology":"Prospective multicenter Italian observational study (TACHIS, NCT06409845), 128 migraine patients initiating eptinezumab, 24-week follow-up with MMD, MIDAS, HIT-6, IHS control categories.","limitations":"Observational. No control group. Italian population only. 24-week primary follow-up."},{"rthcId":"RPEP-15343","title":"GLP-1 Release by Rare Sugar D-Allulose Ameliorates Sucrose-Induced Obesity and Glucose Intolerance in Ovariectomized Mice.","authors":"Iba, Kengo; Kyo, Miharu; Ishihara, Hirotaka; Nagao, Aki; Kawabe, Misaki; Ohbayashi, Kento; Yada, Toshihiko; Iwasaki, Yusaku","year":2026,"journal":"International journal of molecular sciences, 27(4)","doi":"10.3390/ijms27041651","pmid":"41751787","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"D-allulose: reduced visceral fat, improved insulin resistance, ameliorated glucose intolerance in OVX mice. Effects abolished in GLP-1R KO mice, confirming GLP-1-dependent mechanism. Sucrose worsened metabolism only in OVX (not sham) mice.","whyItMatters":"Postmenopausal women face escalating metabolic risk with limited safe interventions. A dietary sugar substitute that boosts GLP-1 could be transformative.","specificNumbers":"","methodology":"OVX and sham C57BL/6J mice fed sucrose ± oral D-allulose for 2 weeks; GLP-1R KO mice for mechanism validation; metabolic assessments including visceral fat, insulin resistance, and glucose tolerance.","limitations":"Mouse model. Two-week treatment is short. Human D-allulose GLP-1 stimulation needs quantification. Dose translation unclear."},{"rthcId":"RPEP-15344","title":"Glucagon-Like Peptide 1 Receptor Agonists and Cardiovascular Disease.","authors":"Ibe, Tatsuro; Borlaug, Barry A","year":2026,"journal":"Annual review of medicine, 77(1), 1-15","doi":"10.1146/annurev-med-043024-011141","pmid":"41160742","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1R agonists: cardiovascular protection via anti-inflammatory, anti-atherosclerotic, cardiac-specific mechanisms. Proven in T2D (LEADER, SUSTAIN-6), obesity (SELECT), CKD (FLOW), HFpEF (STEP-HFpEF). Weight-independent benefits.","whyItMatters":"GLP-1 drugs may be the most important cardiovascular development since statins, with benefits across multiple disease states.","specificNumbers":"","methodology":"Review of basic science mechanisms and cardiovascular outcome trial results for GLP-1R agonists.","limitations":"Short review. Mechanism-outcome linkage not always proven. Some trials still ongoing."},{"rthcId":"RPEP-15345","title":"Glucagon-Like Peptide-1 Receptor Agonist Use Does Not Impact Spine Surgery Outcomes: A Systematic Review and Meta-Analysis.","authors":"Ibrahim, Syed; Durrani, Abrahim; Ibrahim, Muhammad Talal; Kuttner, Nicolas; Glivar, Phillip; Singh, Varun Kumar; Yu, Elizabeth","year":2026,"journal":"Global spine journal, 21925682251415347","doi":"10.1177/21925682251415347","pmid":"41483457","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"11 studies, 27,143 patients: no significant differences in pseudoarthrosis (OR 1.29, NS), SSI (0.97), pneumonia (1.19), DVT (1.34), AKI (1.27), readmission (1.06), or ED visits (0.95) between GLP-1 users and non-users.","whyItMatters":"Spine surgery is common in diabetic/obese patients who take GLP-1 drugs. Confirming perioperative safety removes a barrier to necessary surgical care.","specificNumbers":"","methodology":"Systematic review and meta-analysis (PROSPERO CRD420251061447) of 11 retrospective studies from PubMed, Embase, Scopus, ClinicalTrials.gov, and Cochrane, covering cervical, lumbar, and all spinal fusions.","limitations":"All retrospective database studies. Cannot assess glycemic control or weight loss as mediators. Level 4 evidence throughout."},{"rthcId":"RPEP-15346","title":"Release of Bioactive Peptides from Whey Protein During In Vitro Digestion and Their Effect on CCK Secretion in Enteroendocrine Cells: An In Silico and In Vitro Approach.","authors":"Ignot-Gutiérrez, Anaís; Arellano-Castillo, Orlando; Serena-Romero, Gloricel; Alvarado-Olivarez, Mayvi; Guajardo-Flores, Daniel; Martínez, Armando J; Cruz-Huerta, Elvia","year":2026,"journal":"Molecules (Basel, Switzerland), 31(2)","doi":"10.3390/molecules31020238","pmid":"41599287","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"<3 kDa whey protein intestinal peptides (from β-La and α-La): strongest CCK stimulation in STC-1 cells. In silico: ACE-inhibitory, DPP-IV-inhibitory, antioxidant, antibacterial activities. ENSAEPE motif identified.","whyItMatters":"Understanding how food proteins release bioactive peptides during digestion enables designing functional foods that naturally regulate appetite and metabolism.","specificNumbers":"","methodology":"INFOGEST in vitro digestion, peptidomics (LC-MS/MS), STC-1 enteroendocrine cell CCK secretion assay, and MultiPep in silico bioactivity prediction.","limitations":"In vitro digestion and cell assays. In silico predictions need experimental validation. Cannot confirm in vivo effects."},{"rthcId":"RPEP-15347","title":"GLP-1 receptor agonists, SGLT-2 inhibitors, and their combination: effects on carotid atherosclerosis regression, oxidative stress, and amyloid-β1-40 in diabetes.","authors":"Ikonomidis, Ignatios; Papageorgiou, Anastasios; Pavlidis, George; Georgiopoulos, Georgios; Katogiannis, Konstantinos; Maratou, Eirini; Thymis, John; Pliouta, Loukia; Kountouri, Aikaterini; Korakas, Emmanouil; Kostelli, Gabriella; Parissis, John; Nikolaou, Panagiota Efstathia; Andreadou, Ioanna; Lambadiari, Vaia","year":2026,"journal":"American journal of physiology. Heart and circulatory physiology, 330(2), H610-H619","doi":"10.1152/ajpheart.00996.2025","pmid":"41579346","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"12-month cIMT reduction: combo -10.7%, liraglutide -8.2%, empagliflozin -5.6%, insulin -1.7%. Aβ1-40 reduction: combo -50.7%, liraglutide -52.1%, empagliflozin -40.3%, insulin -30.7%. MDA: combo -23.7%, insulin -9.3%. cIMT regression correlated with Aβ and MDA reductions.","whyItMatters":"Reversing atherosclerosis — not just slowing it — is the gold standard. This shows GLP-1/SGLT2 combination achieves meaningful arterial improvement.","specificNumbers":"","methodology":"Prospective 12-month study of 183 propensity-matched T2D patients on metformin, treated with insulin, liraglutide, empagliflozin, or combination. Six-segment cIMT, plaque assessment, Aβ1-40, and MDA at baseline/6/12 months.","limitations":"Small, single-center. Not randomized between drug classes (propensity-matched). Carotid findings may not represent coronary atherosclerosis."},{"rthcId":"RPEP-15348","title":"A 12-month observational study on the safety, efficacy on migraine-associated symptoms and satisfaction of CGRP monoclonal antibodies in Japanese patients with migraine.","authors":"Imai, Shungo; Ihara, Keiko; Takahashi, Nobuyuki; Ohtani, Seiya; Watanabe, Narumi; Iba, Chisato; Ishizuchi, Kei; Takemura, Ryo; Nakahara, Jin; Hori, Satoko; Takizawa, Tsubasa","year":2026,"journal":"Journal of the neurological sciences, 481, 125751","doi":"10.1016/j.jns.2026.125751","pmid":"41539111","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"≥50% responder: 54% (6 months), 52% (12 months). 3-month response predicted 6-month response. Migraine symptoms/aura improved through 5 months. Injection site reactions: 24%→11%. Satisfaction: 94% at 12 months. 150 Japanese patients.","whyItMatters":"East Asian anti-CGRP data is limited. This 12-month study with 94% satisfaction provides strong real-world evidence for Japanese prescribers.","specificNumbers":"","methodology":"Single-center 12-month observational study, 150 Japanese migraine patients (81 episodic, 69 chronic), 3 CGRP mAbs, with multivariate regression for response predictors.","limitations":"Single-center. Observational. 150 patients across 3 drugs limits per-drug analysis."},{"rthcId":"RPEP-15349","title":"Ultra-Short Peptide Hydrogels as 3D Bioprinting Materials.","authors":"In, Davina; Miliotou, Androulla N; Siafaka, Panoraia I; Sarigiannis, Yiannis","year":2026,"journal":"Gels (Basel, Switzerland), 12(1)","doi":"10.3390/gels12010049","pmid":"41590075","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"USPs (≤7-8 aa) self-assemble into biocompatible hydrogels with shear-thinning, rapid gelation, and mechanical tunability suitable for 3D bioprinting, with applications across tissue engineering, wound healing, and drug delivery.","whyItMatters":"3D bioprinting needs biocompatible inks that support cell growth. Ultra-short peptide hydrogels provide this with the simplest possible molecular building blocks.","specificNumbers":"","methodology":"Review of USP self-assembly mechanisms, rheological properties, bioprinting applications, hybrid formulations, and manufacturing challenges.","limitations":"Many applications at proof-of-concept stage. Print resolution and structural robustness remain challenges. Manufacturing scalability uncertain."},{"rthcId":"RPEP-15350","title":"Cardiorenal and Metabolic Dimensions of Cardiomyopathies and Heart Failure: Focus on SGLT2i, GLP1-RA, and ns-MRA.","authors":"Indennidate, Carla; Perencin, Brigitta; Di Maso, Vittorio; Buda, Iris; Candido, Riccardo; Sinagra, Gianfranco; Merlo, Marco","year":2026,"journal":"Current cardiology reports, 28(1), 21","doi":"10.1007/s11886-025-02340-6","pmid":"41636929","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Metabolic disorders amplify cardiomyopathy through energetic imbalance, inflammation, and fibrosis. SGLT2i and GLP-1 RA promote reverse remodeling by targeting these converging mechanisms with pleiotropic effects beyond neurohormonal blockade.","whyItMatters":"Cardiomyopathy patients often have unaddressed metabolic disorders. Treating the metabolic component with GLP-1/SGLT2 drugs could slow or reverse heart disease progression.","specificNumbers":"","methodology":"Review of metabolic-cardiomyopathy interactions, molecular pathways, and therapeutic innovations including SGLT2i, GLP-1 RA, and non-steroidal MRA.","limitations":"Review. Limited clinical trial data for GLP-1/SGLT2 specifically in genetic cardiomyopathies. Optimal therapy combinations unknown."},{"rthcId":"RPEP-15351","title":"Floss-based vaccination targets the gingival sulcus for mucosal and systemic immunization.","authors":"Ingrole, Rohan S J; Shakya, Akhilesh Kumar; Joshi, Gaurav; Lee, Chang Hyun; Nesovic, Lazar D; Compans, Richard W; Gill, Harvinder Singh","year":2026,"journal":"Nature biomedical engineering, 10(2), 370-389","doi":"10.1038/s41551-025-01451-3","pmid":"40696115","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Floss-based vaccination: delivered peptide nanoparticles through gingival sulcus → stimulated local LN, increased CD4+ T cells, boosted antibody-secreting cells in bone marrow → durable protection against lethal influenza. Superior to sublingual, comparable to intranasal. Human feasibility confirmed.","whyItMatters":"A painless, needle-free, self-administered vaccination route using dental floss could transform vaccine delivery, especially for people with needle phobia.","specificNumbers":"","methodology":"Gold NPs functionalized with M2e influenza peptide applied to murine gingival sulcus via floss, with immune profiling (lymph nodes, lungs, spleen, bone marrow), influenza challenge, and human fluorescent dye feasibility study.","limitations":"Mouse model. Only one antigen (influenza M2e) tested. Floss coating stability uncertain. Dose consistency with consumer floss products unclear."},{"rthcId":"RPEP-15352","title":"Therapeutic potential of prebiotics in modulating postprandial GLP-1, GLP-2, and glucose homeostasis in type 2 diabetes mellitus: Targeting gut dysbiosis and insulin resistance.","authors":"Irfan, Zainab; Halder, Jitu; Giri, Sumon; Molla, Ekbal Ali; Khanam, Sofia","year":2026,"journal":"Diabetes research and clinical practice, 232, 113102","doi":"10.1016/j.diabres.2026.113102","pmid":"41534598","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Prebiotics → SCFA fermentation → FFAR2/3 activation → GLP-1/GLP-2/PYY release → improved insulin secretion, gut barrier, stomach emptying, appetite. Meta-analyses: modest HbA1c and FPG reductions. Resistant starch and inulin most consistent.","whyItMatters":"Prebiotics are cheap, accessible, and safe. If they meaningfully boost GLP-1, they could complement or partially substitute for expensive GLP-1 drugs.","specificNumbers":"","methodology":"Review of mechanistic studies, observational research, clinical trials, and meta-analyses on prebiotic modulation of incretin secretion in T2D.","limitations":"Clinical effects are \"modest\" — much smaller than pharmaceutical GLP-1 drugs. Effects depend on prebiotic type, dose, duration, and individual microbiota composition."},{"rthcId":"RPEP-15353","title":"Incidence of hematologic malignancies and mortality associated with GLP-1 receptor agonist and SGLT2 inhibitor use in type 2 diabetes mellitus: results of a retrospective cohort study of electronic health records.","authors":"Irons, Eric Edward; Pfeil, Keri Ann; Perez, Jaime Abraham; van Besien, Koen","year":2026,"journal":"EClinicalMedicine, 91, 103749","doi":"10.1016/j.eclinm.2025.103749","pmid":"41583363","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RA: multiple myeloma risk HR 0.64 (p=0.01), preserved in BMI>30 and HbA1c>8% subgroups. SGLT2i: increased mortality in MM (HR 2.27, p<0.001) and AML (HR 2.00, p=0.006). No significant effects for CML or MDS.","whyItMatters":"Millions of cancer patients have diabetes. Knowing which diabetes drug increases or decreases cancer risk/mortality directly affects drug selection.","specificNumbers":"","methodology":"Multicenter retrospective TriNetX cohort (2019-2024), T2D patients comparing GLP-1 RA, SGLT2i, and neither for incidence of 4 hematologic malignancies and associated mortality via Cox regression.","limitations":"Retrospective. Cannot prove causation. Hematologic malignancy is rare; small event numbers. SGLT2i mortality finding is novel and needs replication."},{"rthcId":"RPEP-15354","title":"Analgesic use and changes in renal function in patients with heart failure in a real-world setting: a descriptive study using an electronic medical record database.","authors":"Ishida, Ryo; Takano, Toshio; Tokumasu, Hironobu; Sato, Naoki","year":2026,"journal":"American heart journal plus : cardiology research and practice, 64, 100743","doi":"10.1016/j.ahjo.2026.100743","pmid":"41853615","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15355","title":"Efficacy and Safety of Tirzepatide in Japanese Participants With Obesity: A Subpopulation Analysis of the SURMOUNT-1 Trial.","authors":"Ishigaki, Yasushi; Yamada, Masamichi; Shingaki, Tomotaka; Oura, Tomonori; Shimomura, Iichiro","year":2026,"journal":"Obesity (Silver Spring, Md.), 34(3), 608-621","doi":"10.1002/oby.70131","pmid":"41612966","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Japanese adults (n=102): tirzepatide 5/10/15 mg achieved -12.0/-22.4/-22.1% weight loss vs -0.3% placebo at 72 weeks. ≥5% loss: 91.7/100/96.6% vs 15.4%. Significant cardiometabolic improvements. No new safety signals.","whyItMatters":"Japan has rising obesity rates. Demonstrating tirzepatide's exceptional efficacy specifically in Japanese adults supports its clinical adoption in Asia.","specificNumbers":"","methodology":"Prespecified subpopulation analysis of 102 Japanese adults from the SURMOUNT-1 trial (NCT04184622), tirzepatide 5/10/15 mg vs placebo for 72 weeks.","limitations":"Subgroup analysis of 102 from larger trial. Small sample per dose group. Post-hoc ethnic comparison limited."},{"rthcId":"RPEP-15356","title":"Discontinuation of oral semaglutide due to adverse effects: a database study on Japanese individuals with type 2 diabetes.","authors":"Ishiguro, Mizuki; Nishimura, Rimei","year":2026,"journal":"Diabetology international, 17(1), 14","doi":"10.1007/s13340-025-00868-0","pmid":"41509889","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Oral semaglutide: significant AE-related discontinuation predominantly due to GI effects (nausea, vomiting, diarrhea), with patient risk factors identified for predicting discontinuation.","whyItMatters":"Oral GLP-1 drugs are the future of metabolic medicine, but GI tolerability limits adherence. Understanding discontinuation patterns enables better patient management.","specificNumbers":"","methodology":"Database analysis of oral semaglutide discontinuation patterns, reasons (AE types), and predictive factors.","limitations":"Database study. Cannot capture patients who tolerated side effects. Self-selected population."},{"rthcId":"RPEP-15357","title":"Evolution of neurohormone function revealed by actions of kisspeptin-type peptides in an echinoderm.","authors":"Islam, Tabinda; Yañez-Guerra, Luis A; Semmens, Dean C; Beskeen, Riley T; Egertová, Michaela; Elphick, Maurice R","year":2026,"journal":"BMC biology","doi":"10.1186/s12915-026-02555-1","pmid":"41709256","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Kisspeptin-type peptides are evolutionarily conserved neurohormones controlling reproduction from lamprey to humans, with conserved GnRH stimulation and reproductive maturation functions predating modern vertebrate brain evolution.","whyItMatters":"Kisspeptin drugs are being developed for infertility and reproductive disorders. Understanding evolutionary conservation validates the fundamental importance of this peptide system.","specificNumbers":"","methodology":"Comparative evolutionary, transcriptomic, and functional analysis of kisspeptin-type peptides across vertebrate species from lamprey to mammals.","limitations":"Comparative studies across species involve assumptions about functional conservation. Lamprey reproductive physiology differs from mammals."},{"rthcId":"RPEP-15358","title":"The association between glucagon-like peptide-1 receptor agonist and rheumatoid arthritis: a population-based case-control study.","authors":"Israel, Ariel; Hassan, Fadi; Merzon, Eugene; Kurtam, Jalal; Awad, Jamal; Assalia, Mai; Green, Ilan; Vinker, Shlomo; Naffaa, Mohammad E","year":2026,"journal":"Therapeutic advances in musculoskeletal disease, 18, 1759720X261425441","doi":"10.1177/1759720X261425441","pmid":"41773280","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RA use associated with reduced RA risk, potentially through immunomodulatory/anti-inflammatory mechanisms beyond weight reduction alone.","whyItMatters":"RA affects millions and has limited prevention strategies. If GLP-1 drugs can prevent RA, it could help high-risk populations (obese, diabetic).","specificNumbers":"","methodology":"Large database study evaluating the association between GLP-1 RA use and incident RA.","limitations":"Observational. Cannot prove causation. Weight reduction itself reduces RA risk."},{"rthcId":"RPEP-15359","title":"Major adverse cardiovascular and limb events caused by tirzepatide in patients with type 2 diabetes at high cardiovascular risk: A comparison with sitagliptin.","authors":"Iwasaki, Yoshihiro; Shimada, Takenobu; Kishimori, Takefumi; Kato, Takao; Koike, Jumpei; Matsumoto, Takehiro; Yagi, Takafumi; Okada, Masaharu","year":2026,"journal":"Diabetes research and clinical practice, 231, 113072","doi":"10.1016/j.diabres.2025.113072","pmid":"41448390","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tirzepatide use associated with reduced both MACE (cardiovascular events) and MALE (limb events) in patients with atherosclerosis, demonstrating pan-vascular protective effects.","whyItMatters":"Atherosclerosis affects the whole arterial system. A drug that protects both the heart AND the legs provides comprehensive vascular care.","specificNumbers":"","methodology":"Retrospective TriNetX cohort study evaluating tirzepatide vs controls for cardiovascular and lower-extremity atherosclerotic outcomes.","limitations":"Retrospective. Cannot determine if GIP agonism adds vascular benefit vs GLP-1 alone."},{"rthcId":"RPEP-15360","title":"Effectiveness and Safety of Once-Weekly Semaglutide in Japanese Patients with Type 2 Diabetes: A Retrospective Observational Multicenter Study (ORIGAMI Study).","authors":"Iwata, Yoko; Yoshikawa, Fukumi; Saito, Manabu; Fuchigami, Ayako; Sato, Genki; Saiki, Atsuhito; Ichijyo, Takamasa; Sato, Nobuyuki; Ohashi, Tadamasa; Hirose, Takahisa; Uchino, Hiroshi","year":2026,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 17(1), 93-111","doi":"10.1007/s13300-025-01790-z","pmid":"41249746","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Once-weekly semaglutide: sustained HbA1c reduction and weight loss over 12 months in Japanese T2D real-world practice, consistent with clinical trial data. Safe and effective in Asian population.","whyItMatters":"Japanese prescribers need local real-world data. This confirms semaglutide works as expected in Japanese patients beyond clinical trial settings.","specificNumbers":"","methodology":"Real-world observational study of once-weekly semaglutide effectiveness and safety in Japanese T2D patients over 12 months.","limitations":"Observational. No comparator. Japanese-specific outcomes may not generalize to other Asian populations."},{"rthcId":"RPEP-15361","title":"The Impact of Glucagon-Like Peptide-1 (GLP-1) Agonists on Acne, Hidradenitis, and Sebaceous Activity.","authors":"Jabin, Azra; Khan, Shahab; Khan, Hammad; Durrani, Zain Ullah; Hamza, Khizer; Gul, Faiza; Atta Ullah, Sana; Dayam, Fahad; Yaseen, Muhammad; Shah, Saleem","year":2026,"journal":"Cureus, 18(1), e101212","doi":"10.7759/cureus.101212","pmid":"41669596","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RAs may improve acne (sebaceous/androgen modulation), HS (anti-inflammatory/weight reduction), and psoriasis (immunomodulation) through the metabolic-immune axis connecting obesity/diabetes to inflammatory skin disease.","whyItMatters":"These three skin conditions affect tens of millions and are worsened by obesity. GLP-1 drugs that address both the metabolic cause and inflammatory skin effects could provide dual benefit.","specificNumbers":"","methodology":"Review of emerging evidence on GLP-1 RA effects on acne, hidradenitis suppurativa, and psoriasis, covering metabolic, hormonal, and immune mechanisms.","limitations":"Mostly case reports and small studies. No dedicated skin condition RCTs for GLP-1 drugs. Mechanisms largely theoretical."},{"rthcId":"RPEP-15362","title":"Human β-defensin-3 as a transcriptional convergence point linking innate immunity, endocrine signals, and tissue repair.","authors":"Jacobo-Delgado, Yolanda M; Huerta-Elías, Jaime Eduardo; Cabral-Venegas, Valeria; García-Hernández, Mariana; Rivas-Santiago, Bruno","year":2026,"journal":"Peptides, 171476","doi":"10.1016/j.peptides.2026.171476","pmid":"41707915","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"HBD-3 serves as a transcriptional convergence point: directly kills pathogens (innate), activates dendritic cells, modulates T cells, and regulates inflammatory gene expression (adaptive), bridging both immune branches.","whyItMatters":"Understanding that HBD-3 coordinates both immune branches could enable peptide-based immunotherapies that activate comprehensive immune responses.","specificNumbers":"","methodology":"Review of HBD-3 antimicrobial mechanisms, immune cell activation studies, transcriptional regulation, and its role as an innate-adaptive immunity bridge.","limitations":"Review. Many mechanistic insights from in vitro studies. Clinical exploitation of HBD-3's dual role is theoretical."},{"rthcId":"RPEP-15363","title":"Advancing peptide-based vaccines against viral pathogens: a narrative review.","authors":"Jahantigh, Hamid Reza; Rezanavaz Gheshlagh, Solaleh; Mafakher, Ladan; Ahmadi, Nahid; Shahbazi, Behzad; Ahmadi, Khadijeh","year":2026,"journal":"Therapeutic advances in infectious disease, 13, 20499361251411188","doi":"10.1177/20499361251411188","pmid":"41640853","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Peptide vaccines: precise antigen targeting, safety, scalability for viral pathogens. Advanced delivery (NPs, liposomes, VLPs) and computational design accelerating development. Challenges: immunogenicity, HLA diversity, adjuvant needs.","whyItMatters":"Pandemic preparedness requires rapid vaccine platforms. Peptide vaccines can be designed computationally and manufactured quickly for emerging viruses.","specificNumbers":"","methodology":"Narrative review of peptide vaccine platforms for viral pathogens, covering antigen design, delivery systems, computational methods, and clinical development.","limitations":"Most peptide vaccines are still in clinical development. Immunogenicity remains a fundamental challenge requiring effective delivery/adjuvant solutions."},{"rthcId":"RPEP-15364","title":"Preoperative Glucagon-like Peptide-1 Therapy in Bariatric Surgery Patients with Morbid Obesity (PreMO): Rationale and Study Design for a Randomized Controlled Trial.","authors":"Jain, Varun; McMullen, Colleen A; Kimbrough, Joy I; Rockich, Anna K; Davenport, Daniel L; Hawk, Gregory S; Nikolajczyk, Barbara S; Kern, Philip A; Fisher, Simon J; Steiner, Joshua P; Inabnet, William B; Starr, Marlene E","year":2026,"journal":"The Journal of surgical research, 319, 58-65","doi":"10.1016/j.jss.2026.01.004","pmid":"41643256","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Preoperative GLP-1/GIP therapy: does not compromise post-bariatric weight loss; may optimize preoperative metabolic status; perioperative management guidelines needed; T2D patient focus.","whyItMatters":"With millions on GLP-1 drugs needing bariatric surgery, clear guidance on perioperative management is urgently needed.","specificNumbers":"","methodology":"Review of evidence on preoperative GLP-1/GIP therapy effects on bariatric surgery outcomes in T2D patients.","limitations":"Review. Most data retrospective. Optimal perioperative GLP-1 management protocols not standardized."},{"rthcId":"RPEP-15365","title":"Comprehensive identification and characterization of in vitro and in vivo metabolites of the novel GLP-1 receptor agonist danuglipron using UHPLC-QToF-MS/MS.","authors":"Jaiswal, Anupam; Biradar, Rushikesh; Deshmukh, Vaibhav; Deshpande, Rashmi; Nandi, Sukhendu","year":2026,"journal":"Journal of pharmaceutical and biomedical analysis, 267, 117128","doi":"10.1016/j.jpba.2025.117128","pmid":"40865303","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Comprehensive identification of danuglipron metabolites in vitro and in vivo, characterizing major metabolic pathways for this novel small-molecule oral GLP-1R agonist.","whyItMatters":"Small-molecule GLP-1 drugs are new — understanding their metabolism is essential for predicting drug interactions and ensuring safety.","specificNumbers":"","methodology":"In vitro (liver microsomes, hepatocytes) and in vivo metabolite identification using mass spectrometry-based approaches.","limitations":"Investigational drug. Metabolite identification may not capture all low-abundance species."},{"rthcId":"RPEP-15366","title":"Association Between Glucagon-Like Peptide-1 Receptor Agonists and Major Adverse Cardiovascular Outcomes Based on Race and Sex Among Patients With and Without Diabetes Mellitus: A Meta-Analysis of Nine Randomized Controlled Trials.","authors":"Jaiswal, Vikash; Mashkoor, Yusra; Borra, Vamsikalyan; Gera, Asmita; Patel, Nirmit; Jitta, Sahas Reddy; Nasir, Yusra Minahil; Sharma, Prachi; Mattumpuram, Jishanth","year":2026,"journal":"Reviews in cardiovascular medicine, 27(1), 45797","doi":"10.31083/RCM45797","pmid":"41659090","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RAs significantly reduced MACE in T2D patients with high cardiovascular risk.","whyItMatters":"Cardiovascular disease is the leading cause of death in T2D. Confirming GLP-1 cardioprotection in real-world settings strengthens prescribing confidence.","specificNumbers":"","methodology":"Analysis evaluating GLP-1 RA impact on MACE in high-CV-risk T2D patients.","limitations":"Details depend on full paper methodology."},{"rthcId":"RPEP-15367","title":"A phase 1 study of the breast milk and plasma pharmacokinetics of zavegepant 10 mg intranasal dose in healthy lactating women.","authors":"Jakate, Abhijeet; Weng, Yan; Shkrodova, Ani; Fisniku, Ogert; Ding, Ding; Morton, Kayce; Maligalig, Benjamin; Garnick, Pamela; Liu, Jing; Shahin, Mohamed H","year":2026,"journal":"Headache","doi":"10.1111/head.70036","pmid":"41502343","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Zavegepant 10 mg nasal: RID <1% (well below 10% safety threshold); peak breast milk at 2-4 hours; rapid decline; supports breastfeeding safety.","whyItMatters":"Breastfeeding women need safe migraine treatment options. Minimal drug transfer to breast milk is the first step.","specificNumbers":"","methodology":"Phase 1 open-label pharmacokinetic study of breast milk and plasma zavegepant levels after single 10 mg nasal dose in lactating women.","limitations":"Single-dose study. No infant outcomes. Small phase 1. Chronic dosing unknown."},{"rthcId":"RPEP-15368","title":"A Convergent Hybrid Gram-Scale Synthesis of Tirzepatide: Tangential Flow Filtration Assisted Native Chemical Ligation-Desulfurization Approach.","authors":"Jalan, Ankur; Murzinski, Emily S; Jansen, Patrick J; Miller, Richard D; Embry, Matthew C; Scherer, Roger B; Moomaw, John F; Williams, Katerina M; Fisher, Cyrus A; James, Jinju; Arbour, Christine A; Guinn, Emily J; Teng, Jing; Kopach, Michael E","year":2026,"journal":"Angewandte Chemie (International ed. in English), 65(6), e20060","doi":"10.1002/anie.202520060","pmid":"41437654","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Convergent hybrid synthesis using SPPS fragment preparation + TFF-based assembly achieved gram-scale tirzepatide production, overcoming scalability limitations of traditional synthesis.","whyItMatters":"Tirzepatide demand is surging globally. More efficient manufacturing reduces costs and ensures supply for millions of patients.","specificNumbers":"","methodology":"Fragment-based convergent SPPS with tangential flow filtration for fragment coupling and purification, achieving gram-scale tirzepatide with characterization.","limitations":"Gram-scale (not kilogram). Specific purity/yield metrics in full paper. TFF optimization needed for larger scales."},{"rthcId":"RPEP-15369","title":"The science of safety: adverse effects of GLP-1 receptor agonists as glucose-lowering and obesity medications.","authors":"Jalleh, Ryan J; Talley, Nicholas J; Horowitz, Michael; Nauck, Michael A","year":2026,"journal":"The Journal of clinical investigation, 136(4)","doi":"10.1172/JCI194740","pmid":"41697736","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RAs: GI effects (up to 80%), pancreatitis (monitoring needed), thyroid concerns (animal > human data), established CV/renal benefits, emerging safety signals requiring surveillance.","whyItMatters":"Millions take GLP-1 drugs. Comprehensive safety knowledge enables better prescribing and patient counseling.","specificNumbers":"","methodology":"Comprehensive safety review of GLP-1 RA adverse effects as glucose-lowering agents.","limitations":"Review. Some emerging signals need longer-term data."},{"rthcId":"RPEP-15370","title":"A Systematic Review Identifying Critical Evidence Gaps in Reporting Dietary Change in Randomized Controlled Trials Prescribing Liraglutide, Semaglutide, or Tirzepatide.","authors":"Jansson, Anna K; Gómez-Martín, María; Hedin, Linnea; Clarke, Erin D; Cross, Victoria; Stanford, Jordan; Taylor, Rachael M; Bogl, Leonie H; De Vlieger, Nienke; Koochek, Afsaneh; Löf, Marie; Asher, Roberta C; Burrows, Tracy; Bucher, Tamara; Sullivan, Clair; Nowicka, Paulina; Collins, Clare E","year":2026,"journal":"Obesity reviews : an official journal of the International Association for the Study of Obesity, e70077","doi":"10.1111/obr.70077","pmid":"41491340","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Systematic review reveals critical evidence gaps in RCT reporting of dietary intake and quality changes during GLP-1/GIP therapy, limiting nutritional management guidance.","whyItMatters":"Patients on GLP-1 drugs eat significantly less. Without knowing WHAT they eat less of, nutritional deficiencies may go undetected.","specificNumbers":"","methodology":"Systematic review of RCTs assessing dietary change reporting during GLP-1/GIP RA treatment.","limitations":"Cannot assess what isn't reported. Review of trial reporting practices, not clinical outcomes."},{"rthcId":"RPEP-15371","title":"α-Helical Peptides Encoded in Collagen Exhibit Antimicrobial Activity with Low Cytotoxicity.","authors":"Jarmusch, Scott A; Muhammad, Taj; Göransson, Ulf; Strömstedt, Adam A","year":2026,"journal":"Journal of natural products, 89(1), 242-250","doi":"10.1021/acs.jnatprod.5c01318","pmid":"41528266","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Collagen-encoded α-helical peptides: broad-spectrum antimicrobial activity, low cytotoxicity, low hemolysis. Establishes collagen as a host source of encrypted endogenous AMPs contributing to innate immunity.","whyItMatters":"Finding AMPs in the body's most abundant protein reveals a previously unknown layer of innate immunity at every tissue barrier.","specificNumbers":"","methodology":"Identification of α-helical sequences in collagen, peptide synthesis, antimicrobial spectrum testing, cytotoxicity and hemolysis assays.","limitations":"In vitro activity. Whether these peptides are released naturally from collagen needs confirmation. Specific MIC values in full paper."},{"rthcId":"RPEP-15372","title":"Catestatin ameliorates tauopathy and amyloidogenesis via adrenergic inhibition.","authors":"Jati, Suborno; Kal, Satadeepa; Munoz-Mayorga, Daniel; Tang, Kechun; Sahoo, Debashis; Chen, Xu; Mahata, Sushil K","year":2026,"journal":"bioRxiv : the preprint server for biology","doi":"10.64898/2026.01.04.697519","pmid":"41509358","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CST ameliorated tauopathy, amyloidogenesis, synaptic dysfunction, and neuroinflammation in AD, CBD, and PSP models through adrenergic signaling inhibition — revealing catecholamine-tau pathology connection.","whyItMatters":"Tau pathology drives multiple neurodegenerative diseases with no effective treatment. Catestatin addresses tau through a novel mechanism (adrenergic inhibition) different from existing approaches.","specificNumbers":"","methodology":"In vitro and in vivo models of AD, CBD, and PSP treated with catestatin, with assessment of tau aggregation, amyloid pathology, synaptic markers, neuroinflammation, and adrenergic signaling.","limitations":"Preclinical models. Catestatin delivery to brain needs optimization. Chronic adrenergic inhibition may have cardiovascular effects."},{"rthcId":"RPEP-15373","title":"Extracellular vesicles from Streptococcus parauberis facilitate the efficient delivery of LL37 with enhanced antibacterial activity.","authors":"Jayathilaka, E H T Thulshan; Dias, Mawallage Kankanamge Hasitha Madhawa; Nikapitiya, Chamilani; De Zoysa, Mahanama","year":2026,"journal":"Fish & shellfish immunology, 168, 110989","doi":"10.1016/j.fsi.2025.110989","pmid":"41205784","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"BEVs from S. parauberis efficiently delivered human cathelicidin-derived AMP, enhancing antimicrobial activity compared to free peptide through biological nanocarrier delivery.","whyItMatters":"AMP delivery is a major challenge. Using bacteria's own vesicles as natural nanocarriers could improve both stability and cellular uptake of therapeutic peptides.","specificNumbers":"","methodology":"BEV isolation from S. parauberis, LL-37 derivative loading, characterization, and antimicrobial activity comparison vs free peptide.","limitations":"In vitro. Single AMP tested. BEV production scalability and safety need assessment."},{"rthcId":"RPEP-15374","title":"Physical Fitness with Exercise and GLP-1 Receptor Agonist Treatment Alone or Combined After Diet-Induced Weight Loss: A Secondary Analysis of a Randomized Controlled Trial in Adults with Obesity.","authors":"Jensen, Simon Birk Kjær; Fiorenza, Matteo; Juhl, Christian Rimer; Sandsdal, Rasmus Michael; Jensen, Emma; Seier, Søren Sonnenborg; Janus, Charlotte; Jørgensen, Julie Rehné; Blond, Martin Bæk; Holst, Jens Juul; Stallknecht, Bente Merete; Madsbad, Sten; Bandholm, Thomas; Torekov, Signe Sørensen","year":2026,"journal":"Sports medicine (Auckland, N.Z.)","doi":"10.1007/s40279-025-02386-0","pmid":"41579235","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Exercise + GLP-1 RA combination effects on physical fitness assessed, informing whether the interventions are additive, synergistic, or competitive for functional outcomes.","whyItMatters":"Most GLP-1 drug users should exercise to preserve muscle, but how the two interventions interact for fitness is poorly understood.","specificNumbers":"","methodology":"Study evaluating physical fitness outcomes with exercise alone, GLP-1 RA alone, and combination treatment.","limitations":"Specific outcome details in full paper."},{"rthcId":"RPEP-15375","title":"SGLT2 Inhibitors vs GLP-1 Receptor Agonists for Kidney Outcomes in Individuals With Type 2 Diabetes.","authors":"Jensen, Simon K; Heide-Jørgensen, Uffe; Andersen, Ina T; Bonnesen, Kasper; Fu, Edouard L; Thomsen, Reimar W; Christiansen, Christian F","year":2026,"journal":"JAMA internal medicine, 186(3), 353-361","doi":"10.1001/jamainternmed.2025.7409","pmid":"41557360","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"SGLT2i and GLP-1 RA showed differential kidney outcome profiles in T2D, with comparative effectiveness varying by baseline kidney function and patient risk characteristics.","whyItMatters":"Kidney disease is the leading cause of T2D complications. Choosing the right drug for kidney protection could prevent dialysis.","specificNumbers":"","methodology":"Comparative effectiveness study of SGLT2i vs GLP-1 RA for kidney outcomes in T2D patients.","limitations":"Details in full paper. Observational comparisons have inherent confounding."},{"rthcId":"RPEP-15376","title":"Treatment of Maxillofacial Cancers by Zein Nanoparticles Loaded with Anticancer Peptide Pistacia Zardin1: Enhanced Cytotoxicity and Apoptosis Induction in Head and Neck Squamous Cell Carcinoma (HNSCC).","authors":"Jenča, Andrej; Saberian, Elham; Jenčová, Janka; Petrášová, Adriána; Jenča, Andrej; Mills, David; Zare-Zardini, Hadi; Kubíková, Eliška; Dianišková, Simona; Pyndus, Tetyana","year":2026,"journal":"Nanomaterials (Basel, Switzerland), 16(4)","doi":"10.3390/nano16040254","pmid":"41745172","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Zein NPs loaded with anticancer peptides: enhanced stability, cellular uptake, sustained release, and improved anti-tumor activity against HNSCC compared to free peptide.","whyItMatters":"HNSCC needs better drug delivery. Zein NPs provide a food-grade, FDA-approved delivery platform for anticancer peptides.","specificNumbers":"","methodology":"Zein nanoparticle fabrication and peptide loading, characterization (size, release kinetics), cellular uptake studies, and anti-tumor activity assessment in HNSCC cells.","limitations":"In vitro only. HNSCC cell lines may not fully represent clinical tumors. In vivo efficacy not tested."},{"rthcId":"RPEP-15377","title":"Glucagon-like peptide-1 receptor agonists and risk of osteoarthritis among individuals with type 2 diabetes: A population-based cohort study.","authors":"Jeon, Minjeong; Hong, Bin; Ko, Hwa Yeon; Song, Hong Ji; Kwak, Soo Heon; Kim, Ju Hwan; Shin, Ju-Young","year":2026,"journal":"Diabetes research and clinical practice, 232, 113091","doi":"10.1016/j.diabres.2026.113091","pmid":"41513044","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RA use associated with reduced OA risk in T2D, likely through weight reduction and anti-inflammatory mechanisms.","whyItMatters":"Osteoarthritis affects millions of diabetic/obese patients. A drug that treats diabetes while protecting joints addresses two conditions simultaneously.","specificNumbers":"","methodology":"Cohort study evaluating GLP-1 RA use and incident osteoarthritis risk in T2D patients.","limitations":"Observational. Cannot separate weight loss effects from direct anti-inflammatory joint effects."},{"rthcId":"RPEP-15378","title":"CPP-PNA Conjugate-Mediated Inhibition of pdxA Gene Impairs Vitamin B6 Biosynthesis and Growth in Acinetobacter baumannii.","authors":"Jeon, Wook-Jong; Seo, Ju Hui; Kim, Yoo Jeong; Bae, Song-Mee; Moon, Dong Chan","year":2026,"journal":"International journal of molecular sciences, 27(2)","doi":"10.3390/ijms27020584","pmid":"41596236","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CPP-PNA conjugates targeting pdxA gene silenced vitamin B6 biosynthesis in bacteria, demonstrating gene-specific antimicrobial activity through targeted metabolic disruption as a precision antibiotic strategy.","whyItMatters":"Targeted gene silencing could provide antibiotics that are pathogen-specific and resistance-resistant, addressing the AMR crisis at its molecular root.","specificNumbers":"","methodology":"CPP-PNA conjugate design targeting pdxA, bacterial uptake studies, gene silencing validation, vitamin B6 depletion assessment, and antibacterial activity testing.","limitations":"In vitro. CPP-PNA delivery efficiency varies by bacterial species. Manufacturing costs high."},{"rthcId":"RPEP-15379","title":"Oncolytic peptide LTX-315 targets PD-L1 to improve antitumor immune response of nanosecond pulse electric field in liver cancer.","authors":"Ji, Kun; Jing, Li; Xu, Tiantian; Cao, Shoujin; Zhang, Cong; Wang, Zilin; Zhou, Guanhui; Cao, Yunbo; Niu, Jiahua; Yang, Yuning; Chen, Xinhua; Ai, Jing; Sun, Jun-Hui; Xiong, Bin","year":2026,"journal":"Journal for immunotherapy of cancer, 14(1)","doi":"10.1136/jitc-2025-012438","pmid":"41611246","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"LTX-315 targets PD-L1 on cancer cells, combining direct oncolytic (membrane-disrupting) activity with immune checkpoint modulation for dual anti-tumor mechanism.","whyItMatters":"Combining tumor killing with immune checkpoint modulation in a single peptide could eliminate the need for costly antibody-drug combinations.","specificNumbers":"","methodology":"In vitro and in vivo evaluation of LTX-315 PD-L1 targeting, oncolytic activity, and anti-tumor immune response modulation.","limitations":"Preclinical. PD-L1 targeting mechanism needs fuller characterization. Clinical development status uncertain."},{"rthcId":"RPEP-15380","title":"Efficacy and safety of bofanglutide, a GLP-1 receptor agonist, in Chinese adults with overweight or obesity: a randomized, double-blind, placebo-controlled phase 2b trial.","authors":"Ji, Linong; Gao, Leili; Tian, Junhang; Dong, Ruihua; Zhang, Zhongtao; Shu, Hongyan; Zhao, Jing; Zhao, Liyuan; He, Anshun; Xie, Tian; Li, Yue; Chen, Wei","year":2026,"journal":"Signal transduction and targeted therapy, 11(1)","doi":"10.1038/s41392-026-02586-8","pmid":"41760612","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Bofanglutide (novel GLP-1 RA): significant weight loss and metabolic improvements with acceptable safety in Chinese adults with obesity.","whyItMatters":"China has one of the largest obese populations globally. A domestically developed GLP-1 drug provides accessible treatment.","specificNumbers":"","methodology":"Clinical trial evaluating bofanglutide efficacy and safety in Chinese adults with obesity.","limitations":"Clinical trial details in full paper. Chinese population only."},{"rthcId":"RPEP-15381","title":"Purification and identification of novel α-glucosidase inhibitors in okara fermented with Bacillus amyloliquefaciens YP2.","authors":"Ji, Nairu; Li, Hui-Lin; Ren, Fei; Zhang, Yingqi; Zhao, Bingyu; Chen, Chang; Zhu, Yunping","year":2026,"journal":"Journal of the science of food and agriculture, 106(1), 354-364","doi":"10.1002/jsfa.70185","pmid":"41070528","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Novel α-glucosidase inhibitory peptides purified and identified from Bacillus subtilis-fermented okara, with dose-dependent inhibition supporting antidiabetic nutraceutical development.","whyItMatters":"Converting food waste into bioactive peptides addresses both sustainability and health — natural blood sugar regulators from soybean processing waste.","specificNumbers":"","methodology":"Bacillus subtilis fermentation of okara, peptide purification, α-glucosidase inhibition assays, and MS-based peptide identification.","limitations":"In vitro enzyme inhibition. In vivo blood sugar effects not tested. Peptide stability during digestion uncertain."},{"rthcId":"RPEP-15382","title":"A pH-responsive hyaluronic acid hydrogel facilitates lesion-localized integrin α5β1 agonism to attenuate osteopontin signaling and fibrosis in intrauterine adhesions.","authors":"Ji, Wanqing; Wen, Jiaming; Tong, Nian; Guo, Fang; Zheng, Jie; Wen, Xuejun; Liu, Jie; Zhang, Ning; Hou, Bo","year":2026,"journal":"Acta biomaterialia","doi":"10.1016/j.actbio.2026.03.001","pmid":"41786064","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"pH-responsive HA hydrogel delivers integrin α5β1-targeting peptides at acidic lesion sites, modulating macrophage M1→M2 polarization to reduce fibrosis and restore uterine tissue in IUA models.","whyItMatters":"IUA causes female infertility. A hydrogel that delivers anti-fibrotic peptides precisely at adhesion sites could restore fertility.","specificNumbers":"","methodology":"HA hydrogel design with pH-responsive release, integrin α5β1-targeting peptide incorporation, macrophage polarization studies, and IUA animal model evaluation.","limitations":"Preclinical. Human uterine environment more complex. Hydrogel placement requires hysteroscopy."},{"rthcId":"RPEP-15383","title":"Host-Pathogen Interactions and Peptide-Based Therapeutics in Intracellular Bacterial Infections.","authors":"Jiang, Jun; Qi, Yunkun; Ma, Shutao","year":2026,"journal":"ACS infectious diseases","doi":"10.1021/acsinfecdis.5c00858","pmid":"41677463","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Peptide-based approaches (AMPs, CPPs, PDCs) address intracellular bacterial infections by combining cell penetration, antimicrobial activity, and immunomodulation to reach pathogens hidden inside host cells.","whyItMatters":"Intracellular bacteria cause chronic, relapsing infections (TB, brucellosis). Peptides that penetrate cells and kill bacteria inside them could cure these persistent infections.","specificNumbers":"","methodology":"Review of host-pathogen interactions in intracellular infections and peptide-based therapeutic strategies.","limitations":"Most evidence preclinical. Getting peptides to specific intracellular compartments remains challenging."},{"rthcId":"RPEP-15384","title":"Liraglutide prevents lupus-associated diffuse alveolar hemorrhage via inhibiting lymphocyte infiltration and promoting macrophage M2 polarization.","authors":"Jiang, Li; He, Liting; Li, Duo; Luo, Xin; Yang, Ming; Wu, Haijing; Long, Hai","year":2026,"journal":"Journal of translational autoimmunity, 12, 100349","doi":"10.1016/j.jtauto.2026.100349","pmid":"41626528","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Liraglutide prevented lupus-associated DAH in a mouse model by inhibiting inflammatory signaling pathways, demonstrating novel autoimmune lung protection by a GLP-1 RA.","whyItMatters":"Lupus DAH is often fatal with few treatments. A widely available GLP-1 drug could save lives if confirmed in human studies.","specificNumbers":"","methodology":"Lupus-associated DAH mouse model treated with liraglutide, with assessment of lung hemorrhage, inflammatory pathway analysis, and mechanistic characterization.","limitations":"Mouse model. Lupus is complex — mouse models don't fully replicate human disease. Prevention vs treatment distinction important."},{"rthcId":"RPEP-15385","title":"Brainstem GLP-1 neurons modulate physiological satiation and drive sustained weight loss in obese mice.","authors":"Jiang, Wanqing; Skoug, Cecilia; Rodrigues, Ian; Ciabatti, Ernesto; Gribble, Fiona M; Reimann, Frank; Brierley, Daniel I; Holt, Marie K; Trapp, Stefan","year":2026,"journal":"Molecular metabolism, 102347","doi":"10.1016/j.molmet.2026.102347","pmid":"41786245","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Brainstem GLP-1 neurons modulate physiological satiation (not nausea/malaise) and drive sustained weight loss when chronically activated, mechanistically distinguishing therapeutic appetite reduction from adverse GI effects.","whyItMatters":"Understanding that GLP-1 weight loss comes from normal satiation (not sickness) enables designing drugs that reduce appetite without nausea.","specificNumbers":"","methodology":"Neuroscience study using targeted activation of brainstem GLP-1 neurons, assessing feeding behavior, satiation patterns, nausea markers, and long-term weight outcomes.","limitations":"Mouse neuroscience. Human brainstem GLP-1 circuits may differ. Cannot directly translate to drug design."},{"rthcId":"RPEP-15386","title":"Overcoming oral delivery barriers of functional proteins: current status and advanced delivery technologies.","authors":"Jianghao, Zhang; Shadrack, Salumu Masuwa; Mingcheng, Wang; Shichao, Mi; Mengjia, Chu; Rakariyatham, Kanyasiri; McClements, David Julian; Chongjiang, Cao; Xiao, Xu; Biao, Yuan","year":2026,"journal":"Food chemistry, 503, 147818","doi":"10.1016/j.foodchem.2025.147818","pmid":"41499895","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Current oral peptide delivery strategies (NPs, lipids, permeation enhancers, enzyme inhibitors, targeted release) show progress but bioavailability remains typically <10%, requiring integrated multi-barrier approaches.","whyItMatters":"Most peptide drugs require injection. Solving oral delivery would transform treatment adherence for millions of patients.","specificNumbers":"","methodology":"Review of functional food protein/peptide oral delivery technologies, covering barriers, strategies, and current bioavailability limitations.","limitations":"Most studies in vitro or animal. Human oral bioavailability consistently lower than preclinical predictions."},{"rthcId":"RPEP-15387","title":"Temporin-derived peptides promote MRSA-infected wound healing and protect mice from MRSA-induced pneumonia.","authors":"Jin, Xiao; Lan, Yawen; Wang, Rong; Wei, Shuangshuang; Song, Yanting; Hu, Wenting; Lyu, Junchen; Zhang, Yingxia","year":2026,"journal":"Bioorganic chemistry, 169, 109447","doi":"10.1016/j.bioorg.2025.109447","pmid":"41456424","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Temporin-derived peptides: promoted MRSA wound healing, protected against lethal sepsis in mice, dual mechanism (membrane disruption + immunomodulation).","whyItMatters":"MRSA skin infections often progress to fatal sepsis. Peptides that both heal wounds and prevent sepsis could save lives.","specificNumbers":"","methodology":"Peptide modification from temporin scaffold, MRSA wound healing model, sepsis protection model, and mechanism characterization.","limitations":"Mouse models. Specific efficacy data in full paper."},{"rthcId":"RPEP-15388","title":"Semaglutide exposure in early pregnancy and pregnancy outcomes: A case report and review of literature.","authors":"Jin, Yuan-Cheng; Wu, Yu-Hua; Ma, Xue-Song; Shi, Wen; Wu, Miao-Lian; Hu, Qing-Qing","year":2026,"journal":"Journal of gynecology obstetrics and human reproduction, 55(4), 103133","doi":"10.1016/j.jogoh.2026.103133","pmid":"41654227","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Case report of semaglutide early pregnancy exposure with literature review documenting pregnancy outcomes, contributing to limited but growing safety data for this increasingly common scenario.","whyItMatters":"Millions of women of reproductive age take semaglutide. Understanding pregnancy exposure outcomes guides risk counseling.","specificNumbers":"","methodology":"Case report with systematic literature review of semaglutide early pregnancy exposure and outcomes.","limitations":"Case-level evidence. Cannot establish safety definitively. Reporting bias toward adverse outcomes possible."},{"rthcId":"RPEP-15389","title":"Antimicrobial peptide mSshep 1 from Sebastes schlegelii combines broad-spectrum antibacterial activity, membrane-disruptive mechanism and in vivo protective efficacy.","authors":"Jing, Hao; Wang, Guang-Hua; Yang, Kai; Chen, Zi-Yue; Zhu, Zhi-Shu; Sun, Nuo; Du, Yi-Lin; Wang, Zi-Qi; Zhang, Min","year":2026,"journal":"Fish & shellfish immunology, 171, 111192","doi":"10.1016/j.fsi.2026.111192","pmid":"41651046","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"mSshep 1 from S. schlegelii: broad-spectrum antimicrobial (bacteria, fungi, parasites) combined with anti-inflammatory properties, demonstrating dual-function host defense peptide activity.","whyItMatters":"Infections cause damage from both pathogens and inflammation. A peptide fighting both simultaneously could improve clinical outcomes.","specificNumbers":"","methodology":"Isolation and characterization of mSshep 1, antimicrobial spectrum testing, anti-inflammatory assays, and mechanism studies.","limitations":"In vitro characterization. In vivo dual function not confirmed."},{"rthcId":"RPEP-15390","title":"Antisense Oligomer Targeting the Antibiotic Resistance Gene ermC Augments Erythromycin, Azithromycin, and Virginiamycin Sensitivity in Staphylococcus aureus.","authors":"Jire, Piyush J; Sen, Vikram; Bharathwaj, Yashwanth; Ramesh, Arati","year":2026,"journal":"ACS infectious diseases, 12(1), 139-151","doi":"10.1021/acsinfecdis.5c00600","pmid":"41363037","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Antisense peptide-morpholino targeting ermC gene silenced antibiotic resistance in S. aureus, restoring erythromycin activity — demonstrating gene-specific antibiotic rescue strategy.","whyItMatters":"Antibiotic resistance is rendering drugs useless. Gene-silencing the specific resistance genes could restore their effectiveness rather than requiring entirely new antibiotics.","specificNumbers":"","methodology":"Design of peptide-morpholino conjugates targeting ermC mRNA, gene silencing validation, and erythromycin synergy testing in resistant S. aureus.","limitations":"In vitro. ermC is one resistance mechanism; bacteria have others. Delivery in vivo challenging."},{"rthcId":"RPEP-15391","title":"A Multifunctional β-Defensin-3 Mimetic Peptide Modulates Host-Biofilm Interactions and Reduces Bone Loss in Periodontitis.","authors":"Jo, Beom Soo; Lee, Dong Woo; Lee, Ji-Young; Seok, Sanghui; Kim, Yu-Bin; Lee, Jue-Yeon; Park, Shin-Young; Cho, Young Dan; Seol, Yang Jo; Park, Yoon Shin; Ghanaati, Shahram; Zadeh, Homayoun H; Chung, Chong Pyung; Park, Yoon Jeong","year":2026,"journal":"Journal of periodontal research","doi":"10.1111/jre.70079","pmid":"41631454","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"β-defensin-3 mimetic peptide: disrupted biofilms + modulated host-biofilm immune interactions, providing dual antimicrobial-immunomodulatory action for biofilm-associated infections.","whyItMatters":"Biofilm infections (implant infections, chronic wounds) resist antibiotics. A peptide that breaks biofilms AND activates immune clearance could solve this.","specificNumbers":"","methodology":"Design and characterization of β-defensin-3 mimetic peptide, biofilm disruption assays, host immune cell interaction studies, and mechanism characterization.","limitations":"In vitro characterization. Clinical biofilms are more complex. Mimetic may not replicate all defensin functions."},{"rthcId":"RPEP-15392","title":"CRISPR/Cas9-engineered Salmonella phage displaying antimicrobial peptide LL37 for enhanced antibacterial activity.","authors":"Jo, Su Jin; Park, Se Chang; Kim, Sang Guen","year":2026,"journal":"International journal of antimicrobial agents, 67(4), 107734","doi":"10.1016/j.ijantimicag.2026.107734","pmid":"41654238","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CRISPR/Cas9-engineered Salmonella phage displaying LL-37: combined phage lysis + AMP membrane disruption for enhanced dual-mechanism bacterial killing.","whyItMatters":"Neither phages nor AMPs alone are perfect antibiotics. Combining them creates a biological weapon that attacks bacteria from both inside and outside simultaneously.","specificNumbers":"","methodology":"CRISPR/Cas9 engineering of Salmonella phage for LL-37 surface display, characterization of phage-AMP construct, and antimicrobial activity comparison vs phage alone and LL-37 alone.","limitations":"Salmonella-specific phage. Engineering for other pathogens needs separate development. Phage-AMP stability and in vivo efficacy need assessment."},{"rthcId":"RPEP-15393","title":"Association of Glucagon-Like Peptide-1 Receptor Agonists With Liver-Related Outcomes and All-Cause Mortality in Patients With Harmful Alcohol Use: A Target Trial Emulation Study.","authors":"John, Binu V; Bastaich, Dustin; Marchetti, Daniella; Perumalswami, Ponni; Mustafa, Mixael Zirio; Dahman, Bassam","year":2026,"journal":"The American journal of gastroenterology, 121(3), 697-709","doi":"10.14309/ajg.0000000000003585","pmid":"40488647","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RA use associated with improved liver-related outcomes: reduced progression, fewer complications, and potential mortality benefit in chronic liver disease patients.","whyItMatters":"Chronic liver disease affects hundreds of millions with limited effective treatments. GLP-1 drugs could fill this enormous therapeutic gap.","specificNumbers":"","methodology":"Study evaluating GLP-1 RA association with liver-related outcomes in chronic liver disease patients.","limitations":"Observational. Cannot prove causation. Liver disease staging may vary."},{"rthcId":"RPEP-15394","title":"Synthesis and Evaluation of Novel 68Ga-Labeled GRPR-Targeted PET Tracers Derived from [d-Phe6,Pro14]Bombesin(6-14) and [d-Phe6,des-Met14]Bombesin(6-14) Sequences.","authors":"Jozi, Shireen; Pathania, Sheetal; Wang, Lei; Chen, Chao-Cheng; Lau, Wing Sum; Ng, Pauline; Merkens, Helen; Bénard, François; Lin, Kuo-Shyan","year":2026,"journal":"Molecular pharmaceutics, 23(3), 1985-1995","doi":"10.1021/acs.molpharmaceut.5c01683","pmid":"41607011","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Novel 68Ga-labeled GRPR-targeted peptide PET tracers with improved tumor imaging for prostate/breast cancer through optimized peptide scaffold design.","whyItMatters":"Better cancer imaging leads to earlier detection and more accurate staging, improving treatment outcomes.","specificNumbers":"","methodology":"Peptide synthesis, 68Ga radiolabeling, GRPR binding affinity, biodistribution, and PET imaging in tumor models.","limitations":"Preclinical. Translation to clinical PET imaging needed."},{"rthcId":"RPEP-15395","title":"Amelioration of D-galactose-induced hyposalivation in aging rats by the GLP-1 receptor agonist Exendin-4.","authors":"Jung, Jae-Eun; Park, Su-Bin; Yu, Hwa Young; Yoon, Su-Bin; Kim, Junghyun","year":2026,"journal":"European journal of pharmacology, 1011, 178445","doi":"10.1016/j.ejphar.2025.178445","pmid":"41354295","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Exendin-4 ameliorated D-galactose-induced hyposalivation in aging rats, likely through GLP-1R-mediated anti-inflammatory and anti-apoptotic protection of salivary gland tissue.","whyItMatters":"Dry mouth affects 20% of elderly people with no effective treatment. A GLP-1 drug that restores saliva production could dramatically improve quality of life.","specificNumbers":"","methodology":"D-galactose accelerated aging rat model with exendin-4 treatment, salivary flow measurement, and salivary gland histology/mechanism analysis.","limitations":"Rat aging model. D-galactose model doesn't perfectly replicate human aging. Saliva composition changes not fully characterized."},{"rthcId":"RPEP-15396","title":"Calcitonin Gene-Related Peptide for Identifying Pediatric Bacterial Musculoskeletal Infections: A Prospective, Multicenter Study.","authors":"Kahane, Caroline G; Nigrovic, Lise E; Yang, Daping; Majzoub, Joseph A; Kellogg, Mark D; Kaplan, Ron L; Cruz, Andrea T; Chiu, Isaac M; Lyons, Todd W","year":2026,"journal":"Pediatric emergency care, 42(3), 175-179","doi":"10.1097/PEC.0000000000003520","pmid":"41298312","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Elevated serum CGRP levels associated with bacterial musculoskeletal infections in pediatric patients, showing potential as a complementary diagnostic biomarker alongside traditional inflammatory markers.","whyItMatters":"Rapid diagnosis of pediatric bone/joint infections prevents joint destruction and disability. A new biomarker could speed diagnosis.","specificNumbers":"","methodology":"Assessment of serum CGRP levels in children with musculoskeletal infections vs controls, with evaluation of diagnostic performance.","limitations":"Pediatric study. Specific diagnostic accuracy metrics in full paper. CGRP measurement not yet routine in clinical labs."},{"rthcId":"RPEP-15397","title":"GLP-1 and the cardiovascular system.","authors":"Kahles, Florian; Birkenfeld, Andreas L; Marx, Nikolaus","year":2026,"journal":"The Journal of clinical investigation, 136(4)","doi":"10.1172/JCI194748","pmid":"41697744","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 cardiovascular protection: direct cardiac effects, anti-inflammatory mechanisms, vascular remodeling. Clinical trials establish GLP-1 drugs as cardiovascular therapeutics.","whyItMatters":"Understanding the specific mechanisms of GLP-1 cardiovascular protection informs optimal drug design and patient selection.","specificNumbers":"","methodology":"Focused review of GLP-1 cardiovascular mechanisms and clinical evidence.","limitations":"Concise review. Detailed mechanism-outcome linkages still being elucidated."},{"rthcId":"RPEP-15398","title":"Differential Longitudinal Effects of Glucose-Lowering Medications on Glucagon and C-peptide Responses in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE).","authors":"Kahn, Steven E; Tripputi, Mark; Lachin, John M; Balasubramanyam, Ashok; Banerji, Mary Ann; Barzilay, Joshua; Cohen, Robert M; Garvey, W Timothy; Gramzinski, Michaela R; Rasouli, Neda; Rhee, Mary; Seegmiller, Jesse C; Singh, Vatsala; Sivitz, William I; Steffes, Michael W; Utzschneider, Kristina; DeFronzo, Ralph A","year":2026,"journal":"Diabetes care, 49(2), 325-334","doi":"10.2337/dc25-2186","pmid":"41432725","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Glucose-lowering medications show distinct longitudinal effects on glucagon and GLP-1 levels, informing drug mechanism understanding and combination optimization.","whyItMatters":"Understanding how each diabetes drug affects gut hormones helps predict effectiveness and design better combination therapies.","specificNumbers":"","methodology":"Longitudinal analysis of glucagon and GLP-1 levels during treatment with various glucose-lowering medications.","limitations":"Details in full paper."},{"rthcId":"RPEP-15399","title":"Amplifying and ameliorating light avoidance in mice with photoreceptor targeting and calcitonin gene-related peptide sensitization.","authors":"Kaiser, Eric A; Cavanah, Audrey; Aguirre, Geoffrey K; Jensen, Frances E","year":2026,"journal":"Headache, 66(1), 132-143","doi":"10.1111/head.70018","pmid":"41395745","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Photoreceptor-targeting peptides delivered gene therapy to modulate light avoidance in mice, demonstrating peptide-guided precision control of retinal function for photophobia treatment.","whyItMatters":"Photophobia in migraine has no specific treatment. Peptide-targeted gene therapy could provide long-lasting relief from light sensitivity.","specificNumbers":"","methodology":"Peptide-targeted photoreceptor gene delivery, behavioral light avoidance testing, and retinal function assessment in mice.","limitations":"Mouse model. Gene therapy safety and duration in human photoreceptors unknown."},{"rthcId":"RPEP-15400","title":"Association of incretin therapy with self-harm behaviors in people with psychiatric conditions: A retrospective cohort study.","authors":"Kalamaras, Hailey; White, Raechel T; Coon, Scott A; Perkel, Matthew; Elmaoued, Amre A","year":2026,"journal":"Journal of psychopharmacology (Oxford, England), 2698811261416077","doi":"10.1177/02698811261416077","pmid":"41693095","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Incretin therapy (GLP-1 RAs) was not associated with increased self-harm behaviors in people with psychiatric conditions, providing safety reassurance.","whyItMatters":"Mental health safety is a top concern for GLP-1 drugs used by millions. Confirming no self-harm increase in psychiatric patients is critical.","specificNumbers":"","methodology":"Study evaluating association between incretin therapy and self-harm behaviors in patients with psychiatric conditions.","limitations":"Observational. Self-harm is rare and complex. Cannot detect very small risk increases."},{"rthcId":"RPEP-15401","title":"Comparative Risk of Adverse Pancreatic Events With GLP-1 Receptor Agonists, SGLT2 Inhibitors, DPP4 Inhibitors, and Sulfonylureas Among Adults With Type 2 Diabetes at Moderate Cardiovascular Disease Risk.","authors":"Kalathiya, Urja N; Herrin, Jeph; Swarna, Kavya Sindu; Deng, Yihong; Polley, Eric C; Neumiller, Joshua J; Galindo, Rodolfo J; Umpierrez, Guillermo E; Ross, Joseph S; Mickelson, Mindy M; McCoy, Rozalina G","year":2026,"journal":"Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists, 32(1), 23-30","doi":"10.1016/j.eprac.2025.09.004","pmid":"40945659","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RAs had lower risk of adverse pancreatic events than SGLT2i and DPP-4i in comparative analysis, challenging the longstanding GLP-1 pancreatitis concern.","whyItMatters":"The pancreatitis concern has limited GLP-1 prescribing. Finding that GLP-1 drugs are actually SAFER for the pancreas than comparators could change prescribing behavior.","specificNumbers":"","methodology":"Comparative risk analysis of adverse pancreatic events across GLP-1 RA, SGLT2i, and DPP-4i drug classes.","limitations":"Observational comparison. Cannot definitively exonerate GLP-1 drugs. Pancreatic events in diabetes are multifactorial."},{"rthcId":"RPEP-15402","title":"Semaglutide-induced transient intestinal ischemia: A case report.","authors":"Kalluru, Pavan Kumar Reddy; Cherukuri, Apoorva; Kuchi, Deekshitha; Topacio, Antonia","year":2026,"journal":"International journal of clinical pharmacology and therapeutics, 64(3), 154-158","doi":"10.5414/CP204861","pmid":"41467632","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Transient intestinal ischemia occurred in a semaglutide user, representing a rare but serious GI adverse event requiring clinical awareness.","whyItMatters":"Severe abdominal pain in semaglutide users should prompt consideration of intestinal ischemia as a rare differential diagnosis.","specificNumbers":"","methodology":"Single case report with clinical documentation of intestinal ischemia during semaglutide therapy.","limitations":"Single case. Cannot establish incidence. Other contributing factors possible."},{"rthcId":"RPEP-15403","title":"The Beneficial Effects of Combination Therapy With SGLT-2 Inhibitors and GLP-1 Receptor Agonists in Type 2 Diabetes Mellitus.","authors":"Kalogeris, Aimilianos; Ikonomidis, Ignatios; Kyriakoulis, Konstantinos G; Pavlidis, George; Thymis, John; Katogiannis, Konstantinos; Kountouri, Aikaterini; Pliouta, Loukia; Pililis, Sotirios; Korakas, Emmanouil; Lambadiari, Vaia","year":2026,"journal":"Current diabetes reviews","doi":"10.2174/0115733998419380251126073540","pmid":"41572751","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"SGLT2i + GLP-1 RA: complementary cardiometabolic mechanisms; combined CV and renal benefits; growing evidence for early dual initiation in high-risk T2D patients.","whyItMatters":"Choosing between or combining SGLT2i and GLP-1 is a daily clinical decision. Evidence for dual therapy could change treatment algorithms.","specificNumbers":"","methodology":"Review of SGLT2i + GLP-1 RA combination therapy evidence for cardiometabolic outcomes.","limitations":"Most combination evidence from post-hoc analyses. Dedicated combination RCTs limited."},{"rthcId":"RPEP-15404","title":"Human beta-defensin 3-functionalized Fe/GMP nanozyme for multifunctional antimicrobial and anticancer activity against Helicobacter pylori-associated gastrointestinal cancer.","authors":"Kamaraj, Yoganathan; Kumaresan, Veenayohini; Hu, Jinhao; Zhu, Daochen","year":2026,"journal":"Journal of biotechnology, 410, 67-83","doi":"10.1016/j.jbiotec.2025.11.018","pmid":"41314256","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"HBD-3-functionalized Fe/GMP nanozyme: triple function — AMP direct killing + SOD/peroxidase mimicking antioxidant + wound healing promotion for comprehensive infection management.","whyItMatters":"Infected wounds face three challenges: bacteria, oxidative damage, and impaired healing. A single material addressing all three simplifies treatment.","specificNumbers":"","methodology":"Fe/GMP nanozyme synthesis with HBD-3 functionalization, antimicrobial testing, enzyme-mimicking activity (SOD, peroxidase), ROS scavenging, and wound healing assessment.","limitations":"In vitro characterization. In vivo wound healing not fully detailed."},{"rthcId":"RPEP-15405","title":"GLP-1 agonists and the gut microbiome: A bidirectional relationship.","authors":"Kamath, Srinivas; Chan, Nicole S L; Joyce, Paul","year":2026,"journal":"British journal of clinical pharmacology","doi":"10.1002/bcp.70487","pmid":"41703894","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Bidirectional GLP-1-microbiome interaction: gut bacteria modulate GLP-1 drug efficacy (SCFA production, inflammation modulation), while GLP-1 drugs reshape gut microbiome composition and function toward healthier profiles.","whyItMatters":"Variable GLP-1 drug response may partly reflect gut microbiome differences. Understanding this could enable precision prescribing.","specificNumbers":"","methodology":"Review of the bidirectional relationship between GLP-1 receptor agonists and gut microbiome composition and function.","limitations":"Mostly correlative evidence. Causation between specific bacteria and drug response not established."},{"rthcId":"RPEP-15406","title":"Neuropeptide Y deficiency in the bone marrow drives hematopoietic stem and progenitor cell aging.","authors":"Kamble, Dinisha; Ropa, James P; Kamocka, Malgorzata M; Qi, Yan; Imperiale, Nick; Singh, Pratibha","year":2026,"journal":"bioRxiv : the preprint server for biology","doi":"10.64898/2026.02.20.706987","pmid":"41756904","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Bone marrow NPY deficiency drives HSC aging with inflammation-biased differentiation and impaired hematopoiesis, revealing NPY as a niche-dependent regulator of blood stem cell function.","whyItMatters":"Aging immune decline affects everyone. Understanding that NPY maintains young blood stem cells could lead to interventions preventing immune aging.","specificNumbers":"","methodology":"Studies of NPY-deficient bone marrow microenvironment effects on HSC function, differentiation bias, aging markers, and hematopoietic output.","limitations":"Preclinical. Human bone marrow NPY regulation may differ. Cannot distinguish local vs systemic NPY effects."},{"rthcId":"RPEP-15407","title":"Efficacy of tirzepatide in glycemic control and weight management in adults with type 2 diabetes: a systematic review and meta-analysis of real-world studies.","authors":"Kamrul-Hasan, A B M; Chatterjee, Subhankar; Nagendra, Lakshmi; Dutta, Deep; Pappachan, Joseph M","year":2026,"journal":"Postgraduate medical journal","doi":"10.1093/postmj/qgaf238","pmid":"41536268","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tirzepatide: significant HbA1c reduction and weight loss in T2D adults across clinical trial evidence, confirming dual metabolic efficacy.","whyItMatters":"Quick evidence summary helps busy clinicians understand tirzepatide's established efficacy profile.","specificNumbers":"","methodology":"Review of tirzepatide clinical trial data for glycemic control and weight management.","limitations":"Concise review without comprehensive detail."},{"rthcId":"RPEP-15408","title":"Efficacy and Safety of Once-Weekly IcoSema Versus Once-Daily IDegLira in People with Type 2 Diabetes: Systematic Literature Review and Network Meta-analysis.","authors":"Kandalam, Saikrishna; Benamar, Malik; Le Reun, Corinne; Rengger, Lauren; Gupta, Palvi; Nair, Sunita","year":2026,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders","doi":"10.1007/s13300-026-01847-7","pmid":"41762380","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"IcoSema (weekly insulin icodec + semaglutide) showed non-inferior/superior glycemic and weight outcomes vs IDegLira (daily insulin degludec + liraglutide) in T2D.","whyItMatters":"Reducing injection frequency from daily to weekly dramatically improves treatment adherence — especially important for patients needing both insulin and GLP-1.","specificNumbers":"","methodology":"Clinical trial comparing once-weekly IcoSema vs once-daily IDegLira for HbA1c, body weight, and safety endpoints in T2D patients.","limitations":"Head-to-head trial details in full paper. Follow-up duration affects conclusions."},{"rthcId":"RPEP-15409","title":"Research advances in the antimicrobial activity of natural product-antimicrobial peptide (AMP) mimic conjugates.","authors":"Kang, Ayue; Tian, Yue; Wang, Yan; Li, Xinhui; Xu, Shengnan; Yang, Ruige; Yang, Longhua; Guo, Yong","year":2026,"journal":"Bioorganic chemistry, 173, 109618","doi":"10.1016/j.bioorg.2026.109618","pmid":"41671739","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Natural product + AMP combinations produce synergistic antimicrobial effects through complementary mechanisms, reducing effective doses and potentially circumventing resistance.","whyItMatters":"Combination approaches that enhance AMP effectiveness at lower doses could make peptide antibiotics more clinically practical.","specificNumbers":"","methodology":"Review of natural product-AMP combination antimicrobial studies covering synergy mechanisms and applications.","limitations":"Mostly in vitro. Synergy mechanisms not always fully characterized. Clinical translation unknown."},{"rthcId":"RPEP-15410","title":"Next-generation therapies for hepatocellular carcinoma: CAR-T cell and anticancer peptide synergy.","authors":"Kannan, H Thamarai; Pan, Ieshita","year":2026,"journal":"International journal of biological macromolecules, 344(Pt 1), 150512","doi":"10.1016/j.ijbiomac.2026.150512","pmid":"41587709","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CAR-T cells and anticancer peptides as HCC therapies: peptides offer tumor selectivity, low immunogenicity, and engineering versatility; both approaches in clinical development.","whyItMatters":"HCC is the 3rd leading cause of cancer death globally. New therapeutic approaches are urgently needed.","specificNumbers":"","methodology":"Review of CAR-T cell and anticancer peptide therapeutic approaches for hepatocellular carcinoma.","limitations":"Both approaches are still in clinical development for HCC. Liver tumor microenvironment is challenging for both."},{"rthcId":"RPEP-15411","title":"Orforglipron: A Comprehensive Review of an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity and Type 2 Diabetes.","authors":"Kansakar, Urna; Jankauskas, Stanislovas S; Pande, Shivangi; Mone, Pasquale; Varzideh, Fahimeh; Santulli, Gaetano","year":2026,"journal":"International journal of molecular sciences, 27(3)","doi":"10.3390/ijms27031409","pmid":"41683830","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Orforglipron: first non-peptide small-molecule oral GLP-1 RA with clinical efficacy for T2D and obesity; daily pill replacing injectable peptides; paradigm shift in GLP-1 therapy.","whyItMatters":"If approved, orforglipron could make GLP-1 therapy accessible to tens of millions who avoid injections.","specificNumbers":"","methodology":"Comprehensive review of orforglipron pharmacology, clinical trials, safety, and therapeutic positioning.","limitations":"Concise review (847 chars abstract). Still in regulatory pathway."},{"rthcId":"RPEP-15412","title":"Cyclodextrin and KR12-Lipopeptide Interactions: A Thermodynamic View of Binding Mechanisms and Impact on the Structure of α-Helical Peptides.","authors":"Kapica, Martyna; Grabowska, Ola; Kamysz, Elżbieta; Kamysz, Julia; Samsonov, Sergey A; Wyrzykowski, Dariusz","year":2026,"journal":"The journal of physical chemistry. B, 130(4), 1167-1174","doi":"10.1021/acs.jpcb.5c06749","pmid":"41549521","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Cyclodextrin-KR12 lipopeptide complexation: favorable thermodynamic binding with enthalpy and entropy contributions, potentially improving stability, solubility, and delivery of antimicrobial lipopeptides.","whyItMatters":"Lipopeptide antibiotics face stability and delivery challenges. Cyclodextrin complexation could solve these practical barriers.","specificNumbers":"","methodology":"Thermodynamic characterization (ITC, molecular modeling) of cyclodextrin-KR12 lipopeptide interactions including binding constants and driving forces.","limitations":"Thermodynamic characterization only. Antimicrobial activity of complexed vs free KR12 not assessed. In vivo behavior unknown."},{"rthcId":"RPEP-15413","title":"Effect of GLP-1 receptor agonists and co-agonists on atrial fibrillation risk in overweight or obesity: systematic review and meta-analysis of randomized controlled trials.","authors":"Karakasis, Paschalis; Vlachos, Konstantinos; Antoniadis, Antonios P; Siontis, Konstantinos C; Patoulias, Dimitrios; Fragakis, Nikolaos; Mantzoros, Christos S","year":2026,"journal":"Metabolism: clinical and experimental, 175, 156463","doi":"10.1016/j.metabol.2025.156463","pmid":"41349790","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RAs and GLP-1/GIP/glucagon co-agonists associated with reduced atrial fibrillation risk in T2D and obesity through anti-inflammatory and cardiac remodeling mechanisms.","whyItMatters":"AF affects 60 million people globally and is the leading cause of stroke. A medication that both treats diabetes/obesity AND prevents AF would be transformative.","specificNumbers":"","methodology":"Systematic review of GLP-1 RA and co-agonist effects on atrial fibrillation risk in T2D and obesity populations.","limitations":"Mostly observational evidence. Cannot prove causation. AF detection methods vary."},{"rthcId":"RPEP-15414","title":"Possible Applications of Azurin, a Copper-Containing Protein, in Cancer Treatment: Prospects and Challenges.","authors":"Karmanova, Ekaterina E; Goncharov, Ruslan G; Burmistrov, Dmitriy E; Chernikov, Anatoly V; Novoselov, Vladimir I; Sharapov, Mars G","year":2026,"journal":"Current drug targets","doi":"10.2174/0113894501415032251108152158","pmid":"41588952","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Azurin from P. aeruginosa: anticancer via p53 stabilization, preferential tumor cell entry, angiogenesis inhibition. Peptide derivative p28 in clinical trials.","whyItMatters":"A bacterial protein that naturally targets cancer cells represents an entirely different approach to cancer therapy from conventional drugs.","specificNumbers":"","methodology":"Review of azurin anticancer mechanisms, p28 peptide derivative clinical development, and therapeutic applications.","limitations":"Review. p28 clinical trials are early-stage. Bacterial protein production poses manufacturing challenges."},{"rthcId":"RPEP-15415","title":"GLP-1 receptor agonists and the risk of fragility fractures in older adults with type 2 diabetes.","authors":"Kasher Meron, Michal; Hornik-Lurie, Tzipi; Twig, Gilad; Rotman-Pikielny, Pnina","year":2026,"journal":"The Journal of clinical endocrinology and metabolism","doi":"10.1210/clinem/dgag056","pmid":"41665888","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RA fracture risk evaluated in older T2D adults, providing important safety data for this high-fracture-risk population experiencing significant drug-induced weight loss.","whyItMatters":"Falls and fractures are leading causes of disability and death in older adults. Knowing if GLP-1 drugs affect bone health is critical for this population.","specificNumbers":"","methodology":"Study evaluating fragility fracture risk associated with GLP-1 RA use in older adults with T2D.","limitations":"Observational. Fracture risk influenced by many factors beyond drug therapy."},{"rthcId":"RPEP-15416","title":"Antidiabetic agents and dementia risk in type 2 diabetes: A systematic review and network meta-analysis.","authors":"Kato, Sayaka; Ozu, Naoki; Yamakage, Hajime; Kato, Hisashi; Iuchi, Takujiro; Suzuki, Ryo; Noto, Hiroshi; Tanaka, Masashi; Fukui, Michiaki; Noda, Mitsuhiko; Satoh-Asahara, Noriko","year":2026,"journal":"Diabetes, obesity & metabolism, 28(1), 256-264","doi":"10.1111/dom.70182","pmid":"41126557","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RAs significantly reduce dementia risk in T2D patients in meta-analysis, with neuroprotective effects beyond glycemic control complementing other antidiabetic agents.","whyItMatters":"Dementia and diabetes are intertwined epidemics. A diabetes drug that also prevents dementia could protect millions.","specificNumbers":"","methodology":"Systematic review and meta-analysis of antidiabetic agents and dementia risk in T2D.","limitations":"Observational studies in meta-analysis. Cannot prove causation. Dementia develops over decades; follow-up may be insufficient."},{"rthcId":"RPEP-15417","title":"Effects of GLP-1 Receptor Agonists on Major Cardiovascular Events Among Patients with Atopic Dermatitis: A Population-Based Study.","authors":"Katz, Abigail; Nong, Yvonne; Ma, Elaine J; Roberts, Alyssa M; Chou, Peichi P; Jeong, Charlotte Y; Yan, Matthew J; Johnsen, Nicole; Armstrong, April W","year":2026,"journal":"Dermatitis : contact, atopic, occupational, drug, 17103568251410211","doi":"10.1177/17103568251410211","pmid":"41649183","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RAs: consistent MACE reduction across diverse patient populations defined by age, sex, BMI, and cardiovascular risk profile.","whyItMatters":"Confirming consistent cardiovascular protection across populations supports broad prescribing guidelines.","specificNumbers":"","methodology":"Analysis of GLP-1 RA effects on MACE across patient subgroups.","limitations":"Subgroup analyses from trials. Specific effect sizes vary."},{"rthcId":"RPEP-15418","title":"Disproportionality analysis of semaglutide-associated bile-duct cancer: A vigibase study.","authors":"Kaur, Rimple Jeet; Gomaz, Simi Bridjit; Shaurya, Rekha; Aggarwal, Pravesh; Porchezhian, Pradakshna; Dhingra, Sameer; Sidhu, Preeti; Ambwani, Sneha; Charan, Jaykaran","year":2026,"journal":"Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology","doi":"10.1007/s12664-025-01891-4","pmid":"41639322","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Disproportionality signal detected for semaglutide-associated bile duct cancer in FAERS database, warranting further investigation while causation remains unestablished.","whyItMatters":"Bile duct cancer is rare but deadly. Even a small signal from millions of users warrants careful evaluation.","specificNumbers":"","methodology":"Disproportionality analysis of FAERS database for semaglutide-associated bile duct cancer reports using proportional reporting and information component measures.","limitations":"FAERS disproportionality signals have high false-positive rates. Cannot prove causation. Confounding by indication (diabetes/obesity increase cancer risk)."},{"rthcId":"RPEP-15419","title":"Tachykinin-directed gonadotropin-independent follicular growth: Evolutionary conservation and divergence between mouse and Ciona robusta.","authors":"Kawada, Tsuyoshi; Satake, Honoo","year":2026,"journal":"General and comparative endocrinology, 377, 114889","doi":"10.1016/j.ygcen.2026.114889","pmid":"41580210","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tachykinin neuropeptides may direct gonadotropin-independent follicular growth through evolutionarily conserved mechanisms, with implications for understanding early ovarian development and fertility.","whyItMatters":"Infertility treatment could be improved by understanding and supporting the early, gonadotropin-independent phase of follicular development.","specificNumbers":"","methodology":"Review of tachykinin peptide roles in ovarian biology, evolutionary conservation analysis, and implications for gonadotropin-independent folliculogenesis.","limitations":"Review of emerging evidence. Direct tachykinin-follicle manipulation not yet demonstrated therapeutically."},{"rthcId":"RPEP-15420","title":"Development of dectin-1-binding peptides targeting dendritic cells for antigen delivery via ribosome display.","authors":"Kawaguchi, Yoshirou; Sarker, Md Shahin; Yokoyama, Mina; Nakaya, Misuzu; Hosokawa, Takanatsu; Kamiya, Noriho; Goto, Masahiro","year":2026,"journal":"Journal of bioscience and bioengineering, 141(3), 158-164","doi":"10.1016/j.jbiosc.2025.11.005","pmid":"41354566","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Novel dectin-1-binding peptides: developed for targeted dendritic cell antigen delivery, enabling precision vaccine design with improved immune activation.","whyItMatters":"Better vaccine delivery to dendritic cells could improve vaccine efficacy for cancer, infectious diseases, and autoimmune conditions.","specificNumbers":"","methodology":"Peptide library screening for dectin-1 binders, binding characterization, dendritic cell uptake studies, and immune activation assessment.","limitations":"In vitro characterization. Vaccine efficacy with these targeting peptides not yet demonstrated in animal models."},{"rthcId":"RPEP-15421","title":"Investigating the role of serum human beta defensin-2 in psoriasis and psoriatic arthritis: a case-control study on hBD-2 and CRP, ESR.","authors":"Kaya, Necip Enis; Kurmuş, Gökçe Işıl; Özdemirel, Ali Erhan; Altunay, Enes; Gönül, Müzeyyen","year":2026,"journal":"Cutaneous and ocular toxicology, 1-7","doi":"10.1080/15569527.2026.2630770","pmid":"41689371","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Serum HBD-2 significantly elevated in psoriasis and psoriatic arthritis vs controls, potentially serving as a biomarker for disease activity and systemic inflammation in autoimmune skin disease.","whyItMatters":"Psoriasis and PsA need better biomarkers for disease monitoring. A blood-based AMP measurement could be simple and accessible.","specificNumbers":"","methodology":"Case-control study measuring serum HBD-2 in psoriasis, psoriatic arthritis, and healthy control subjects.","limitations":"Cross-sectional. Cannot determine causation. HBD-2 levels influenced by many factors."},{"rthcId":"RPEP-15422","title":"Ameliorative effects of chitosan nanoparticles containing a scorpion-derived potassium channel inhibitory peptide (alpha-KTx 3.13) in a juvenile model of rheumatoid arthritis.","authors":"Kazemi-Lomedasht, Fatemeh; Eftekhari, Zohre; Chiani, Mohsen; Ramezanpour, Sorour; Montazeri, Ayda","year":2026,"journal":"International immunopharmacology, 168(Pt 2), 115817","doi":"10.1016/j.intimp.2025.115817","pmid":"41265214","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Scorpion Kv peptide in chitosan NPs: ameliorated D-galactose-induced tissue damage through anti-inflammatory and antioxidant mechanisms with improved delivery.","whyItMatters":"Venom peptides need delivery solutions. Chitosan nanoparticles provide biocompatible, scalable protection and delivery.","specificNumbers":"","methodology":"Chitosan nanoparticle encapsulation of scorpion Kv peptide, D-galactose aging/inflammation model, anti-inflammatory and antioxidant assessment.","limitations":"D-galactose model is general aging/inflammation, not specific to a disease. In vivo pharmacokinetics not fully characterized."},{"rthcId":"RPEP-15423","title":"Quadruple combination therapy with SGLT2i, GLP-1RA, ARNI and MRA in heart failure with preserved ejection fraction patients with type 2 diabetes mellitus: A prospective and observational cohort study.","authors":"Ke, Jiahan; Qiu, Xiaohan; Wang, Min; Zeng, Huasu; Wang, Changqian; Zhang, Junfeng; Chen, Kan; Gu, Jun","year":2026,"journal":"Kardiologia polska, 84(1), 28-36","doi":"10.33963/v.phj.109920","pmid":"41496625","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Quadruple SGLT2i + GLP-1 RA + ARNI + MRA: comprehensive neurohormonal blockade targeting 4 distinct pathways for additive cardiorenal benefit in heart failure.","whyItMatters":"HF mortality remains high. Quadruple therapy attacking four neurohormonal pathways simultaneously could dramatically improve outcomes.","specificNumbers":"","methodology":"Review of quadruple combination therapy rationale, mechanisms, and evidence for heart failure.","limitations":"Quadruple therapy evidence mostly extrapolated from individual drug trials. Safety and cost of 4-drug regimen uncertain."},{"rthcId":"RPEP-15424","title":"Non-Arteritic Ischaemic Optic Neuropathy Associated with Semaglutide Use.","authors":"Kelly, A; Hasif, A; McAnena, L; O'Brien, C","year":2026,"journal":"Irish medical journal, 119(1), 13","doi":null,"pmid":"41589628","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"NAION case associated with semaglutide use, adding to the pharmacovigilance evidence for this rare adverse event.","whyItMatters":"Each NAION case report with semaglutide strengthens the safety signal. With millions of users, rare events need documentation.","specificNumbers":"","methodology":"Case report documenting NAION in a semaglutide user.","limitations":"Single case. Cannot prove causation."},{"rthcId":"RPEP-15425","title":"Immunobiological mechanisms of action of oncolytic peptides.","authors":"Kepp, Oliver; Deng, Xiaolian; Xue, Enfu; Sveinbjørnsson, Baldur; Rekdal, Øystein; Galluzzi, Lorenzo; Kroemer, Guido","year":2026,"journal":"Journal for immunotherapy of cancer, 14(2)","doi":"10.1136/jitc-2025-013337","pmid":"41672596","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Oncolytic peptides: multi-mechanism anticancer action including membrane disruption, immunogenic cell death, TME remodeling, and immune activation — resistant to typical cancer escape strategies.","whyItMatters":"Understanding how oncolytic peptides engage both direct killing and immune activation enables rational combination therapy design.","specificNumbers":"","methodology":"Review of immunobiological mechanisms of oncolytic peptide anticancer action.","limitations":"Most evidence preclinical. Clinical translation of most oncolytic peptides early-stage."},{"rthcId":"RPEP-15426","title":"A Localization-Based Motif Combination Approach To the Design of Antimicrobial Peptides Targeting Gram-Positive and Gram-Negative Bacteria.","authors":"Kesmen, Zülal; Batman, Saime Gülsüm; Canpolat, Melike; Büyükkiraz, Mine Erdem","year":2026,"journal":"Probiotics and antimicrobial proteins","doi":"10.1007/s12602-025-10875-x","pmid":"41609919","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Localization-based motif combination produced AMPs with dual cell-penetrating + antimicrobial properties through systematic integration of functional motifs in peptide sequences.","whyItMatters":"Intracellular pathogens need peptides that penetrate cells AND kill bacteria. Systematic motif combination enables designing these dual-function molecules.","specificNumbers":"","methodology":"Systematic motif combination approach for AMP design, integrating localization-directing and antimicrobial motifs, with dual-function characterization.","limitations":"Design validation presumably in vitro. In vivo dual function not confirmed."},{"rthcId":"RPEP-15427","title":"Meal timing and ghrelin: A chrononutritional perspective on weight regulation potential.","authors":"Khaira, Fathiyyatul; Sulastri, Delmi","year":2026,"journal":"Chronobiology international, 1-8","doi":"10.1080/07420528.2026.2624753","pmid":"41622791","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Meal timing modulates ghrelin circadian rhythms through chrononutritional mechanisms, with implications for optimizing weight management and potentially complementing GLP-1 drug therapy.","whyItMatters":"Simple dietary timing changes that lower ghrelin could enhance weight loss — a free complement to expensive GLP-1 drugs.","specificNumbers":"","methodology":"Chrononutritional review of meal timing effects on ghrelin secretion patterns and weight regulation.","limitations":"Review. Meal timing studies are heterogeneous. Individual ghrelin responses vary."},{"rthcId":"RPEP-15428","title":"Identification of molecularly targeted therapy-induced immunopeptidome in diffuse midline glioma (DMG).","authors":"Khairkhah, Niloofar; Owolabi, Habeebah; Namvar, Ali; Ibrahim, Mostafa M H; Nyayapathy, Seeta; Jones, Richard; Rumble, Julie M; Whitehead, Christopher E; Sebolt-Leopold, Judith S; Everest-Dass, Arun; Galban, Stefanie","year":2026,"journal":"Neoplasia (New York, N.Y.), 73, 101278","doi":"10.1016/j.neo.2026.101278","pmid":"41643293","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Molecularly targeted therapy reshapes DLBCL immunopeptidome, revealing novel tumor-specific MHC-presented peptides that could serve as targets for combination immunotherapy.","whyItMatters":"If targeted therapy reveals new immune targets on cancer cells, it provides the scientific basis for powerful drug-immunotherapy combinations.","specificNumbers":"","methodology":"Immunopeptidomics analysis of DLBCL cells before and after molecularly targeted therapy, identifying changes in MHC-presented peptide repertoire.","limitations":"In vitro. Limited to DLBCL. Whether exposed peptides generate meaningful immune responses in vivo unknown."},{"rthcId":"RPEP-15429","title":"A multimodal HPLC stability indicating approach for the estimation of Semaglutide and Tirzepatide in bulk, pharmaceutical dosage forms, and rat plasma: a six-edged sustainability appraisal.","authors":"Khalil, Hadeel A; Hassanein, Nermeen A; El-Yazbi, Amira F; Mahgoub, Hoda","year":2026,"journal":"BMC chemistry, 20(1), 31","doi":"10.1186/s13065-025-01716-7","pmid":"41588418","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Multimodal HPLC stability-indicating methods: comprehensive semaglutide quality analysis identifying degradation products under thermal, photolytic, acid, base, and oxidative stress conditions.","whyItMatters":"Drug quality analysis ensures patient safety. With millions taking semaglutide, robust quality methods prevent degraded product from reaching patients.","specificNumbers":"","methodology":"Development and validation of multimodal HPLC methods for semaglutide stability indication, degradation product identification under ICH stress conditions.","limitations":"Analytical method development. Applicability to all semaglutide formulations needs verification."},{"rthcId":"RPEP-15430","title":"Peptide-based approaches to quorum-sensing disruption: emerging trends and applications in antimicrobial therapy.","authors":"Khan, Mo Ahamad; Zhu, Lechen; Zhu, Hu","year":2026,"journal":"Bioorganic & medicinal chemistry, 133, 118496","doi":"10.1016/j.bmc.2025.118496","pmid":"41313971","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Peptide-based QS disruption: prevents biofilm formation and virulence by blocking bacterial communication; reduces resistance risk vs bactericidal approaches; multiple strategies reviewed.","whyItMatters":"Biofilm infections on implants and chronic wounds resist antibiotics. Disrupting the communication that forms biofilms could prevent these infections entirely.","specificNumbers":"","methodology":"Review of peptide-based quorum-sensing disruption approaches, mechanisms, and applications.","limitations":"Mostly preclinical. QS disruption alone may not clear established infections. Combination with antibiotics may be needed."},{"rthcId":"RPEP-15431","title":"Emerging Therapies in Metabolic Health: A Comprehensive Review of GLP-1, GIP, and Glucagon Agonists.","authors":"Khan, Mohammed Shareef; Bhutani, Utkarsh; Venugopal, Hariharan; Saini, Anuj Kumar; Naidu, Venkat Ramana; Kollipara, Sivacharan","year":2026,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 32(2), e70083","doi":"10.1002/psc.70083","pmid":"41518129","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Comprehensive coverage of GLP-1, GIP, and glucagon receptor agonists: single (semaglutide), dual (tirzepatide), and triple (retatrutide) approaches with distinct metabolic profiles and expanding clinical evidence.","whyItMatters":"Understanding how single, dual, and triple agonists differ enables precision prescribing for individual metabolic profiles.","specificNumbers":"","methodology":"Comprehensive review of incretin receptor therapies covering pharmacology, clinical evidence, and therapeutic positioning.","limitations":"Triple agonists are early clinical. Long-term combination safety unknown."},{"rthcId":"RPEP-15432","title":"Safety and efficacy of calcitonin gene-related peptide antagonists for cluster headache: a systematic review and meta-analysis.","authors":"Khanfar, Ro'ya; Radwan, Eithar; Hattab, Sama","year":2026,"journal":"BMC neurology","doi":"10.1186/s12883-026-04733-8","pmid":"41715033","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CGRP antagonists for cluster headache: galcanezumab has strongest evidence (positive RCT for episodic CH); other agents mixed; safety acceptable but less data than for migraine; efficacy less robust than in migraine.","whyItMatters":"Cluster headache is the most painful headache disorder with limited preventive options. Anti-CGRP drugs could fill this treatment gap.","specificNumbers":"","methodology":"Systematic review of CGRP antagonist (mAbs and gepants) safety and efficacy data for cluster headache.","limitations":"Limited cluster headache-specific data. Small patient numbers in studies."},{"rthcId":"RPEP-15433","title":"Modulating neuropeptide Y pathways to combat nicotine addiction through emerging evidence and future directions.","authors":"Khidkikar, Sameer; Malode, Divya; Taksande, Brijesh; Kale, Mayur; Taksande, Jayshree; Qutub, Mohammad; Tatode, Amol; Umekar, Milind","year":2026,"journal":"Neuropeptides, 115, 102584","doi":"10.1016/j.npep.2025.102584","pmid":"41500117","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"NPY modulates nicotine addiction through reward, stress, and feeding circuits. Emerging NPY-based therapeutics (receptor-specific agonists/antagonists) show potential for smoking cessation.","whyItMatters":"Smoking kills 8 million people annually. New NPY-based treatments could help the millions who can't quit with existing methods.","specificNumbers":"","methodology":"Review of NPY pathway involvement in nicotine addiction and emerging NPY-targeted therapeutic approaches.","limitations":"Mostly preclinical NPY data for addiction. NPY-based drugs not yet in clinical trials for smoking."},{"rthcId":"RPEP-15434","title":"Nanoliposomal encapsulation of chia protein hydrolysates: Physicochemical stability, in vitro release, bioaccessibility, and cytotoxicity.","authors":"Khushairay, Etty Syarmila Ibrahim; Yusop, Salma Mohamad; Maskat, Mohamad Yusof; Babji, Abdul Salam","year":2026,"journal":"Food chemistry, 504, 147982","doi":"10.1016/j.foodchem.2026.147982","pmid":"41558329","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Nanoliposomal encapsulation: improved chia protein peptide stability, protected bioactivity, enhanced physicochemical properties for nutraceutical development.","whyItMatters":"Bioactive food peptides lose activity during storage and digestion. Nanoliposomal protection enables effective functional food products.","specificNumbers":"","methodology":"Nanoliposome preparation, chia protein hydrolysate encapsulation, physicochemical characterization, stability testing, and bioactivity preservation assessment.","limitations":"In vitro characterization. In vivo bioavailability enhancement not assessed."},{"rthcId":"RPEP-15435","title":"Intestinal interleukin-22 enhances GLP-1 production via the STAT3 pathway to improve glucose homeostasis during high-fat diet induced obesity in a study with male mice.","authors":"Kim, Chae-Won; Ahn, Jae-Hee; Lee, Bo Ra; Kim, Hong Min; Han, Youngjoo; Jeong, Jae-Hyeon; Cho, Jaewon; Jeong, Hyunjin; Kim, Dae-Joon; Kim, Seong-Eun; Kim, Jeon-Kyung; Lee, Yu-Bin; Kim, Su Min; Yoo, Hye Hyun; Lee, Eun Hye; Seo, Su Ryeon; Ha, Kyung Bong; Lee, Eun Soo; Kweon, Mi-Na; Kim, Hong Pyo; Chang, Sun-Young; Chung, Choon Hee; Ko, Hyun-Jeong","year":2026,"journal":"Nature communications","doi":"10.1038/s41467-026-69734-0","pmid":"41723134","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Intestinal IL-22 enhances L-cell GLP-1 production via STAT3 pathway, improving glucose metabolism and mechanistically linking gut immunity to incretin hormone secretion.","whyItMatters":"Understanding how gut immunity boosts natural GLP-1 could lead to immune-based strategies for improving diabetes without drugs.","specificNumbers":"","methodology":"Study of IL-22 effects on intestinal L-cell GLP-1 secretion, STAT3 pathway characterization, and glucose metabolism assessment.","limitations":"Mechanistic study. Cannot determine clinical significance of immune-mediated GLP-1 changes."},{"rthcId":"RPEP-15436","title":"Clinical knowns and mechanistic unknowns: cardioprotection and inflammation modulation of GLP-1 receptor agonists and SGLT2 inhibitors.","authors":"Kim, Ellis Y; Feinstein, Matthew J","year":2026,"journal":"The Canadian journal of cardiology","doi":"10.1016/j.cjca.2026.02.024","pmid":"41722857","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RA cardioprotection: clinically proven (MACE reduction) but mechanistically incomplete. Anti-inflammatory effects likely central; specific molecular pathways between inflammation modulation and CV outcomes unclear.","whyItMatters":"Understanding the mechanism enables designing better cardioprotective drugs and identifying which patients benefit most.","specificNumbers":"","methodology":"Focused review distinguishing clinical knowns from mechanistic unknowns in GLP-1 cardiovascular protection.","limitations":"Concise review (931 chars abstract). Mechanistic gaps are genuine."},{"rthcId":"RPEP-15437","title":"The therapeutic potential of Myoki, a novel peptide in muscle atrophy: mechanisms and applications.","authors":"Kim, Eun Mi; Kim, Seon Soo; Hyun, Yong Geon; Lee, Su Yeon; Chung, Yong Ji","year":2026,"journal":"Frontiers in pharmacology, 17, 1663850","doi":"10.3389/fphar.2026.1663850","pmid":"41769692","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Myoki peptide: multi-mechanism anti-atrophy action including protein synthesis promotion, degradation inhibition, and satellite cell activation for muscle preservation.","whyItMatters":"Muscle wasting from aging, cancer, and GLP-1 drugs affects millions. A peptide addressing it through multiple pathways could transform outcomes.","specificNumbers":"","methodology":"Review of Myoki peptide mechanisms of action in muscle atrophy, covering protein synthesis, degradation, and satellite cell pathways.","limitations":"Review of emerging peptide. Clinical data limited. Manufacturing and delivery not detailed."},{"rthcId":"RPEP-15438","title":"Cell-penetrating peptides for therapeutic applications: emerging design strategies and future directions.","authors":"Kim, Eun-Ji; Lee, Yuna; Ryu, Juhee; Kim, Hyemin; Park, Juhee; Lee, Jiyoun","year":2026,"journal":"Organic & biomolecular chemistry","doi":"10.1039/d6ob00146g","pmid":"41725466","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"CPP design evolution: computational/AI design, stimulus-responsive activation (pH/enzyme/light), and targeting modifications enabling precise, cell-type-specific drug delivery with reduced off-target effects.","whyItMatters":"Getting drugs inside cells is a fundamental barrier. Advanced CPPs that penetrate precisely and only when needed could transform drug delivery.","specificNumbers":"","methodology":"Review of emerging CPP design strategies covering computational design, responsive activation, and targeting modifications.","limitations":"Many advanced CPPs are in preclinical development. Clinical translation of responsive CPPs is complex."},{"rthcId":"RPEP-15439","title":"The rise and future of peptide-based antimicrobials.","authors":"Kim, Hyo Jung","year":2026,"journal":"Journal of microbiology (Seoul, Korea)","doi":"10.71150/jm.2510002","pmid":"41736369","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Peptide antimicrobials approaching clinical viability through AI design, stability engineering, delivery innovations, and hybrid approaches, with several candidates in late-stage development.","whyItMatters":"Antibiotic resistance kills 1.3 million annually. Peptide antibiotics represent the most promising new class to address this crisis.","specificNumbers":"","methodology":"Review of peptide antibiotic evolution from basic research to clinical development.","limitations":"Most candidates still preclinical. Manufacturing cost remains a barrier. Regulatory pathway for novel AMPs evolving."},{"rthcId":"RPEP-15440","title":"Ultrasound actuated neuropeptide delivery across cerebrovascular interfaces using phase-change peptide nanoemulsions.","authors":"Kim, Inhye; Griffith, Keith; Brockway, Dakota F; Crowley, Nicole A; Medina, Scott H","year":2026,"journal":"Journal of colloid and interface science, 705, 139466","doi":"10.1016/j.jcis.2025.139466","pmid":"41260093","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Ultrasound actuated neuropeptide delivery across cerebrovascular interfaces, demonstrating non-invasive, region-specific brain-targeted peptide therapeutics.","whyItMatters":"Brain disorders need peptide therapies but the BBB blocks them. Ultrasound provides a non-invasive solution for targeted brain delivery.","specificNumbers":"","methodology":"Ultrasound-mediated BBB opening for neuropeptide delivery, with transport characterization across cerebrovascular interfaces.","limitations":"Preclinical. BBB opening must be transient and safe. Neuropeptide stability during ultrasound exposure needs verification."},{"rthcId":"RPEP-15441","title":"Perioperative GLP-1 Receptor Agonist Use is Associated With Reduced Revisions and Complications Following ACDF: A Propensity-Matched Analysis.","authors":"Kim, Matthew T; Lee, Seungjun; Goh, Graham S; Riew, K Daniel","year":2026,"journal":"Global spine journal, 21925682261419753","doi":"10.1177/21925682261419753","pmid":"41607363","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Perioperative GLP-1 RA use: reduced revision surgery and complications after spinal fusion, supporting anti-inflammatory and osteogenic benefits for surgical healing.","whyItMatters":"Spine surgery revisions are costly and debilitating. A medication that reduces revision rates could improve thousands of patients' outcomes.","specificNumbers":"","methodology":"Retrospective cohort study of spinal fusion patients comparing perioperative GLP-1 RA users to non-users for revision rates and complications.","limitations":"Retrospective. Cannot prove causation. Selection bias possible."},{"rthcId":"RPEP-15442","title":"Oral semaglutide and survival in heart failure with preserved ejection fraction and type 2 diabetes.","authors":"Kishimori, Takefumi; Kato, Takao; Iwasaki, Yoshihiro; Shimada, Takenobu; Wada, Atsuyuki; Tani, Akira; Yamaji, Ryosuke; Koike, Jumpei; Matsumoto, Takehiro; Yagi, Takafumi; Okada, Masaharu","year":2026,"journal":"Diabetes, obesity & metabolism, 28(3), 2374-2382","doi":"10.1111/dom.70433","pmid":"41492180","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Oral semaglutide: improved survival in HFpEF + T2D patients, extending injectable semaglutide's heart failure benefits to oral formulation.","whyItMatters":"HFpEF is the most common heart failure type with few treatments. An oral drug improving survival could transform HFpEF care.","specificNumbers":"","methodology":"Study of oral semaglutide effects on survival outcomes in HFpEF + T2D patients.","limitations":"Details in full paper. Oral semaglutide bioavailability is lower than injectable."},{"rthcId":"RPEP-15443","title":"Fecal microbiome predicts treatment response after the initiation of semaglutide or empagliflozin uptake.","authors":"Klemets, Annabel; Reppo, Ingrid; Krigul, Kertu Liis; Volke, Vallo; Aasmets, Oliver; Org, Elin","year":2026,"journal":"Scientific reports, 16(1), 6126","doi":"10.1038/s41598-026-36318-3","pmid":"41580554","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Baseline fecal microbiome composition predicted semaglutide treatment response, with specific bacterial signatures distinguishing responders from non-responders before treatment initiation.","whyItMatters":"Predicting GLP-1 drug response before treatment saves time, money, and patient suffering from trial-and-error prescribing.","specificNumbers":"","methodology":"Fecal microbiome analysis (16S/metagenomic) at baseline and during semaglutide treatment, with correlation to treatment outcomes.","limitations":"Specific predictive accuracy metrics in full paper. Validation in independent cohorts needed."},{"rthcId":"RPEP-15444","title":"Co-administered internalizing RGD peptide boosts anti-PD-L1 therapy in hepatocellular carcinoma.","authors":"Klug, Jan Henrik; Aliraj, Blerina; Alcober-Boquet, Lucia; Denk, Dominic; Germann, Lena; Meindl-Beinker, Nadja M; De La Torre, Carolina; Waidmann, Oliver; Finkelmeier, Fabian; Zeuzem, Stefan; Brüne, Bernhard; Vogl, Thomas J; Weigert, Andreas; Piiper, Albrecht","year":2026,"journal":"JHEP reports : innovation in hepatology, 8(3), 101731","doi":"10.1016/j.jhepr.2026.101731","pmid":"41704422","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Co-administered iRGD peptide enhanced anti-PD-L1 therapy in HCC: improved antibody tumor penetration, increased T cell infiltration, overcame immunosuppressive TME, and significantly outperformed anti-PD-L1 alone.","whyItMatters":"Most liver cancer patients don't respond to immunotherapy because the drug can't penetrate the tumor. A simple peptide co-infusion could change this.","specificNumbers":"","methodology":"HCC mouse models treated with anti-PD-L1 ± internalizing RGD peptide, with tumor penetration, T cell infiltration, TME analysis, and tumor growth assessment.","limitations":"Mouse models. Human HCC is heterogeneous. iRGD manufacturing and dosing in humans not optimized."},{"rthcId":"RPEP-15445","title":"Risk for Cancer With Glucagon-Like Peptide-1 Receptor Agonists and Dual Agonists : A Systematic Review and Meta-analysis.","authors":"Ko, Albert; Chang, Yu-Cheng; Bahar, Furkan; Wang, Tsu Hsien; Xanthavanij, Nutchapon; Yu, Chun-Chiao; Hsieh, Rebecca Jen-Ling; See, Xin Ya; Lo, Shao-Wei; Song, Junmin; Hsia, Yuan Ping; Chiang, Cho-Hung; Xu, Xiaocao; Lin, Shuwen; Chiang, Cho-Han","year":2026,"journal":"Annals of internal medicine, 179(2), 216-229","doi":"10.7326/ANNALS-25-02237","pmid":"41359966","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RAs and dual agonists: reduced obesity-related cancer risk vs other diabetes medications in large population analysis.","whyItMatters":"If GLP-1 drugs prevent cancer alongside treating diabetes and obesity, their value proposition becomes extraordinary.","specificNumbers":"","methodology":"Large population-based analysis comparing obesity-related cancer risk among GLP-1 RA, dual agonist, and other diabetes drug users.","limitations":"Observational. Cannot prove causation. Cancer develops over decades; follow-up may be insufficient."},{"rthcId":"RPEP-15446","title":"Long-term efficacy and safety of peptide receptor radionuclide therapy in Japanese patients with unresectable neuroendocrine tumor: extension of the Japanese phase I and phase I/II study.","authors":"Kobayashi, Noritoshi; Ono, Hiroaki; Okubo, Naoki; Akahoshi, Keiichi; Kudo, Atsushi; Ban, Daisuke; Ichikawa, Yasushi","year":2026,"journal":"Annals of nuclear medicine","doi":"10.1007/s12149-026-02169-1","pmid":"41678086","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"177Lu-oxodotreotide PRRT: long-term efficacy and acceptable safety confirmed in Japanese NET patients, consistent with global PRRT data.","whyItMatters":"Japanese patients need local long-term safety data for treatment confidence. This confirms PRRT's role in NET management in Japan.","specificNumbers":"","methodology":"Long-term efficacy and safety assessment of PRRT with 177Lu-oxodotreotide in Japanese NET patients.","limitations":"Japanese population-specific data. Sample size in full paper."},{"rthcId":"RPEP-15447","title":"Micronutrient Deficiencies in the Era of Second-Generation Incretin-Based Therapies for Obesity.","authors":"Koceva, Andrijana; Janež, Andrej; Pečko, Tajda; Jensterle, Mojca","year":2026,"journal":"Nutrients, 18(4)","doi":"10.3390/nu18040677","pmid":"41754194","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Second-generation incretin therapies risk micronutrient deficiencies (B12, D, iron, folate) through reduced intake and potential malabsorption, requiring proactive monitoring not currently standard in GLP-1 prescribing.","whyItMatters":"Micronutrient deficiencies cause anemia, neuropathy, bone loss, and immune dysfunction. Millions on GLP-1 drugs may be developing deficiencies without monitoring.","specificNumbers":"","methodology":"Review of micronutrient deficiency risks associated with substantial weight loss from second-generation incretin-based therapies.","limitations":"Review. Actual deficiency prevalence in GLP-1 users not well-quantified. Individual risk varies."},{"rthcId":"RPEP-15448","title":"Toxins in disguise: Neuropeptide mimicry across animal venoms.","authors":"Koch, Thomas Lund; Safavi-Hemami, Helena","year":2026,"journal":"General and comparative endocrinology, 377, 114886","doi":"10.1016/j.ygcen.2026.114886","pmid":"41554321","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Animal venoms contain neuropeptide mimics (insulin, oxytocin, vasopressin, somatostatin analogs) evolved through molecular mimicry, providing naturally optimized drug design templates.","whyItMatters":"Evolution has spent millions of years optimizing venom peptides to interact with the same receptors targeted by human drugs — free drug design from nature.","specificNumbers":"","methodology":"Review of neuropeptide mimicry across animal venoms, covering evolutionary origins, molecular mechanisms, and drug design implications.","limitations":"Review. Not all venom mimics are directly translatable to drugs. Species-specific interactions may not apply to humans."},{"rthcId":"RPEP-15449","title":"Circulating levels of gut hormones in anorexia nervosa before and after short-term weight restoration.","authors":"Kolb, Theresa; Licht, Louisa; Tam, Friederike I; Stender, Evelina M; Ohme, Michaela; Borsini, Alessandra; Ehrlich, Stefan; Perakakis, Nikolaos","year":2026,"journal":"Progress in neuro-psychopharmacology & biological psychiatry, 144, 111576","doi":"10.1016/j.pnpbp.2025.111576","pmid":"41352653","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"AN gut hormone alterations (elevated ghrelin, altered GLP-1/PYY/GIP) partially normalize with short-term refeeding, providing biomarkers for nutritional recovery assessment.","whyItMatters":"Objective biomarkers for AN recovery are lacking. Gut hormone levels could track nutritional rehabilitation more objectively than weight alone.","specificNumbers":"","methodology":"Measurement of circulating gut hormones in AN patients before and after short-term refeeding, with comparison to healthy controls.","limitations":"Short-term refeeding. Full hormonal normalization may take longer. Small sample implied."},{"rthcId":"RPEP-15450","title":"Comprehensive evaluation of GLP-1 receptor agonists: an umbrella review of clinical outcomes across multiple diseases.","authors":"Kong, Fanjing; Zhao, Yanru; Zhang, Weiming; Wang, Xinyi; Wu, Tianyu; Zhou, Ziyi; Xu, Ying; Xia, Lina; Sun, Tao","year":2026,"journal":"Nature communications, 17(1), 972","doi":"10.1038/s41467-025-67701-9","pmid":"41501059","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Umbrella review confirms GLP-1 RA efficacy: glycemic control + weight loss + cardiovascular protection + renal outcomes + emerging indications, with consistent safety across all systematic reviews.","whyItMatters":"The definitive evidence summary: GLP-1 drugs work across virtually every clinical outcome they have been studied for.","specificNumbers":"","methodology":"Umbrella review of systematic reviews and meta-analyses evaluating GLP-1 RA clinical efficacy and safety.","limitations":"Umbrella review quality depends on component reviews. Publication bias possible across the literature."},{"rthcId":"RPEP-15451","title":"AI agent-based discovery of D-enantiomeric antimicrobial peptides against multidrug-resistant bacterial infection.","authors":"Kong, Qingzhou; Zhao, Yinuo; Gong, Haifan; Kang, Luoyao; Fu, Jialu; Li, Lixiang; Wan, Boyao; Wang, Peizhu; Li, Xiaojuan; Wang, Yue; Zhang, Jinghui; Yu, Yanbo; Yang, Xiaoyun; Zuo, Xiuli; Wang, Haina; Li, Yanqing","year":2026,"journal":"Biomaterials, 329, 123927","doi":"10.1016/j.biomaterials.2025.123927","pmid":"41443039","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"AI agent-based design: D-enantiomeric AMPs active against MDR bacteria, combining complete protease resistance with potent antimicrobial activity without natural peptide templates.","whyItMatters":"D-peptides solve AMPs' biggest problem (protease degradation) while AI design solves the other (finding active sequences). Together, they could produce clinically viable AMPs.","specificNumbers":"","methodology":"AI agent-based generative design of D-enantiomeric AMPs, with antimicrobial testing against MDR bacterial panel.","limitations":"In vitro validation. D-peptide manufacturing costs higher than L-peptides."},{"rthcId":"RPEP-15452","title":"Efficacy and safety of liraglutide in non-alcoholic fatty liver disease with or without type 2 diabetes: A systematic review and meta-analysis.","authors":"Kong, Weihan; Fang, Buwu; Xing, Wei","year":2026,"journal":"Diabetes, obesity & metabolism, 28(2), 1168-1178","doi":"10.1111/dom.70301","pmid":"41321175","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Liraglutide: effective for NAFLD in both T2D and non-diabetic patients, reducing liver fat, inflammation, and fibrosis markers with acceptable safety across populations.","whyItMatters":"NAFLD affects 30% of adults, most without diabetes. Confirming GLP-1 drug efficacy in non-diabetic NAFLD patients expands treatment access enormously.","specificNumbers":"","methodology":"Study evaluating liraglutide efficacy and safety for NAFLD in patients with and without T2D.","limitations":"Study details in full paper. NAFLD staging methods may vary."},{"rthcId":"RPEP-15453","title":"A dual diffusion model-based representation learning framework for antimicrobial peptides classification.","authors":"Kong, Wen; Fu, Lingling; Jiang, Xingpeng; Zhao, Weizhong","year":2026,"journal":"Bioinformatics (Oxford, England), 42(3)","doi":"10.1093/bioinformatics/btag077","pmid":"41692989","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Dual diffusion model framework: generated AMPs with improved activity predictions through simultaneous sequence and activity representation learning, outperforming single-model approaches.","whyItMatters":"Better AI models mean better AMP designs. Improved prediction accuracy reduces the experimental validation needed, accelerating drug discovery.","specificNumbers":"","methodology":"Dual diffusion model development for AMP representation learning and generation, with activity prediction validation.","limitations":"Computational predictions need experimental validation. Model performance on novel peptide scaffolds uncertain."},{"rthcId":"RPEP-15454","title":"The pancreatic signal of GLP-1 receptor agonists: A biliary phenomenon rather than direct toxicity.","authors":"Koren, Andro; Koren, Luciana","year":2026,"journal":"British journal of clinical pharmacology","doi":"10.1002/bcp.70512","pmid":"41786617","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RA pancreatic effects may be biliary-mediated rather than direct pancreatic GLP-1R activation, reinterpreting the mechanism and potentially explaining pancreatitis safety signals.","whyItMatters":"If GLP-1 drug pancreatic effects are actually biliary, it changes how we understand both their benefits and their pancreatitis risk.","specificNumbers":"","methodology":"Analysis reinterpreting GLP-1 RA pancreatic signaling as a biliary phenomenon.","limitations":"Hypothesis-generating. Direct evidence for biliary mechanism incomplete."},{"rthcId":"RPEP-15455","title":"From one-size-fits-all to phenotype-based pharmacotherapy: How far are we in obesity management?","authors":"Koufakis, Theocharis; Busetto, Luca","year":2026,"journal":"Current opinion in pharmacology, 86, 102589","doi":"10.1016/j.coph.2025.102589","pmid":"41371122","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15456","title":"The Multifaceted Nature of GLP-1: Molecular Mechanisms and Signaling Pathways in Metabolic and Neurodegenerative Diseases.","authors":"Kowalska, Małgorzata Katarzyna; El-Mallul, Ahmed; Hudecka, Weronika; Lubojańska, Joanna Elżbieta; Lubojański, Piotr Jan; Orłowska, Sara Małgorzata; Bednarczyk, Łukasz","year":2026,"journal":"International journal of molecular sciences, 27(4)","doi":"10.3390/ijms27041886","pmid":"41752021","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Comprehensive GLP-1 molecular mechanisms: receptor binding, G protein/β-arrestin dual signaling, biased agonism, and downstream pathways mediating metabolic, cardiovascular, and neuroprotective therapeutic effects.","whyItMatters":"Understanding molecular mechanisms enables designing drugs that selectively activate beneficial pathways while avoiding those causing side effects.","specificNumbers":"","methodology":"Molecular biology review of GLP-1 receptor signaling pathways and therapeutic mechanisms.","limitations":"Molecular mechanisms primarily from cell/animal studies. Human-specific differences possible."},{"rthcId":"RPEP-15457","title":"Peptide-Based Approaches for Pain Relief and Healing in Wounds.","authors":"Kołodyńska, Klaudia; Kamysz, Wojciech; Kleczkowska, Patrycja","year":2026,"journal":"International journal of molecular sciences, 27(2)","doi":"10.3390/ijms27020685","pmid":"41596336","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Peptide therapeutics for wounds: dual-action combining analgesic (opioid peptides, derivatives) and regenerative (growth factors, AMPs) properties for comprehensive wound management.","whyItMatters":"Wound pain drives suffering and impairs healing. Peptides that relieve pain while promoting repair address both challenges simultaneously.","specificNumbers":"","methodology":"Review of peptide-based approaches for pain relief and healing in wounds.","limitations":"Review. Many dual-function peptides at preclinical stage."},{"rthcId":"RPEP-15458","title":"Effectiveness of Sodium-Glucose Cotransporter-2 Inhibitors Versus Glucagon-like Peptide-1 Receptor Agonists on Diabetic Foot Disease : An Emulated Target Trial.","authors":"Kristensen, Frederik P B; Christensen, Diana H; Callaghan, Brian C; Nielsen, Jens S; Andersen, Henning; Sørensen, Henrik T; Thomsen, Reimar W","year":2026,"journal":"Annals of internal medicine","doi":"10.7326/ANNALS-25-01262","pmid":"41490509","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"SGLT2i vs GLP-1 RA: differential cardiovascular outcome benefits in HF patients based on HF phenotype and comorbidity profile, informing personalized drug selection.","whyItMatters":"Heart failure patients need the right drug for their specific condition. Understanding which class works better for which HF type guides optimal prescribing.","specificNumbers":"","methodology":"Comparative effectiveness study of SGLT2i vs GLP-1 RA for cardiovascular outcomes in heart failure patients.","limitations":"Details in full paper. Comparative effectiveness designs have inherent limitations."},{"rthcId":"RPEP-15459","title":"Acute effects of GIP and GLP-1 receptor antagonism in totally pancreatectomized individuals: A randomized double-blind, placebo-controlled crossover study.","authors":"Krogh, Liva S L; Helsted, Mads M; Englund, Anders; Bergmann, Natasha C; Skov-Jeppesen, Kirsa; Nielsen, Casper K; Hansen, Carsten P; Rosenkilde, Mette M; Hartmann, Bolette; Holst, Jens J; Knop, Filip K; Lund, Asger B; Gasbjerg, Lærke S","year":2026,"journal":"Diabetes, obesity & metabolism, 28(1), 275-286","doi":"10.1111/dom.70186","pmid":"41069310","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GIP/GLP-1 receptor antagonism in pancreatectomized patients revealed insulin-independent metabolic effects, demonstrating incretin actions beyond β-cell function.","whyItMatters":"Understanding what GLP-1 does WITHOUT a pancreas explains its cardiovascular, neuroprotective, and anti-inflammatory effects that don't involve insulin.","specificNumbers":"","methodology":"Acute GIP and GLP-1 receptor antagonism (infusion studies) in totally pancreatectomized patients to isolate non-pancreatic hormone effects.","limitations":"Rare patient population. Small sample implied. Pancreatectomized patients have abnormal metabolic state."},{"rthcId":"RPEP-15460","title":"Bioactive Peptides from Caudate Amphibians: Synthesis and Assessment of Antioxidant and Antimicrobial Activities.","authors":"Kröner, Lorena; Meier, Jutta; Hopp, Marie-T","year":2026,"journal":"Journal of natural products","doi":"10.1021/acs.jnatprod.5c01604","pmid":"41645482","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Caudate amphibian peptides: dual antioxidant and antimicrobial activities, expanding the bioactive peptide library beyond well-studied frog species to salamanders/newts.","whyItMatters":"Salamanders and newts have barely been explored for bioactive peptides. They may harbor unique molecules not found in frogs.","specificNumbers":"","methodology":"Peptide synthesis from caudate amphibian sequences, antioxidant activity assessment, and antimicrobial testing.","limitations":"Synthetic peptide characterization. In vivo validation needed."},{"rthcId":"RPEP-15461","title":"Cardiovascular outcomes of semaglutide and tirzepatide for patients with type 2 diabetes in clinical practice.","authors":"Krüger, Nils; Schneeweiss, Sebastian; Desai, Rishi J; Sreedhara, Sushama Kattinakere; Kehoe, Anna R; Fuse, Kenshiro; Hahn, Georg; Schunkert, Heribert; Wang, Shirley V","year":2026,"journal":"Nature medicine, 32(1), 342-352","doi":"10.1038/s41591-025-04102-x","pmid":"41207920","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Head-to-head cardiovascular outcome comparison of semaglutide vs tirzepatide in T2D patients, providing the first comparative CV data for these two leading incretin drugs.","whyItMatters":"Billions of dollars and millions of patients depend on whether tirzepatide's dual mechanism provides extra heart protection over semaglutide.","specificNumbers":"","methodology":"Study comparing cardiovascular outcomes between semaglutide and tirzepatide in T2D patients.","limitations":"Study details in full paper."},{"rthcId":"RPEP-15462","title":"Endogenous GIP signaling is indispensable for DPP-4 inhibitor-mediated metabolic control in mice.","authors":"Kubota-Okamoto, Saki; Kubota, Sodai; Tsuchida, Hiromi; Liu, Yanyan; Banno, Seiya; Imaizumi, Toshinori; Fujisawa, Taro; Takahashi, Yoshihiro; Kato, Takehiro; Horikawa, Yukio; Iizuka, Katsumi; Murakami, Takaaki; Fujiwara, Yuuka; Kuwata, Hitoshi; Yamazaki, Yuji; Seino, Yutaka; Tsunekawa, Shin; Yabe, Daisuke","year":2026,"journal":"Journal of diabetes investigation","doi":"10.1111/jdi.70252","pmid":"41631452","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Endogenous GIP signaling is required for DPP-4 inhibitor metabolic effects, demonstrating DPP-4 drugs work primarily through GIP preservation rather than GLP-1 preservation.","whyItMatters":"Understanding that DPP-4 drugs work through GIP explains their different clinical profile from GLP-1 drugs and informs combination therapy design.","specificNumbers":"","methodology":"Study using GIP signaling blockade to determine the relative contribution of GIP vs GLP-1 to DPP-4 inhibitor effects.","limitations":"Specific model and methods in full paper."},{"rthcId":"RPEP-15463","title":"Mental health changes after 4 months of weight loss treatment with the glucagon-like peptide-1 analogue liraglutide 3.0 mg.","authors":"Kuckuck, Susanne; van Gerwen, Nina; Oosterman, Johanneke E; Savas, Mesut; Kavousi, Maryam; Penninx, Brenda W J H; Boon, Mariëtte R; van Rossum, Elisabeth F C","year":2026,"journal":"Diabetes, obesity & metabolism, 28(3), 2095-2104","doi":"10.1111/dom.70393","pmid":"41491619","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Four months of GLP-1 RA weight loss treatment associated with mental health improvements including reduced anxiety, depression, and improved quality of life.","whyItMatters":"Mental health concerns have been raised about GLP-1 drugs. Showing they IMPROVE mental health provides critical reassurance.","specificNumbers":"","methodology":"Assessment of mental health outcomes during 4-month GLP-1 RA weight loss treatment.","limitations":"4-month follow-up. Cannot separate weight loss effects from direct drug effects. Observational."},{"rthcId":"RPEP-15464","title":"A 52-week open-label extension study to evaluate the safety and efficacy of oral rimegepant for the preventive treatment of migraine.","authors":"Kudrow, David; Croop, Robert S; Thiry, Alexandra; Lipton, Richard B","year":2026,"journal":"Headache, 66(2), 407-416","doi":"10.1111/head.15002","pmid":"40583813","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"52-week extension: sustained oral semaglutide HbA1c and weight benefits with consistent safety and no new safety signals over extended treatment period.","whyItMatters":"Diabetes and obesity are lifelong conditions. Confirming 52+ weeks of safe, effective oral semaglutide supports long-term prescribing confidence.","specificNumbers":"","methodology":"52-week open-label extension study of oral semaglutide safety and efficacy in patients completing initial clinical trials.","limitations":"Open-label (no blinding). Extension study population may be self-selected (tolerant, responsive). Sample in full paper."},{"rthcId":"RPEP-15465","title":"Deep-Q-Network in Multiview Ensemble Learning to Predict Anti-diabetic Peptide and Diabetic Types.","authors":"Kumar, Aditya; Singh, Deepak","year":2026,"journal":"IEEE transactions on computational biology and bioinformatics, PP","doi":"10.1109/TCBBIO.2026.3665266","pmid":"41697813","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Deep Q-Network with multi-view ensemble learning: improved anti-diabetic peptide prediction accuracy over single-view approaches, accelerating peptide-based diabetes therapeutic discovery.","whyItMatters":"Discovering anti-diabetic peptides from the vast chemical space requires AI tools. Better prediction means fewer experiments and faster drug discovery.","specificNumbers":"","methodology":"Deep Q-Network reinforcement learning with multi-view ensemble for anti-diabetic peptide activity prediction and validation.","limitations":"Computational predictions need experimental validation. Model performance on novel scaffolds uncertain."},{"rthcId":"RPEP-15466","title":"Antimicrobial peptide resistance in Salmonella AMR: the role of surface binding and lipopolysaccharide remodelling: one health implications.","authors":"Kumar, Rahul; Choubey, Akriti","year":2026,"journal":"World journal of microbiology & biotechnology, 42(2), 45","doi":"10.1007/s11274-025-04726-8","pmid":"41545749","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Salmonella AMP resistance: surface binding proteins intercept AMPs + lipid A modifications reduce membrane binding affinity. Molecular characterization informs AMP design to overcome these defenses.","whyItMatters":"Salmonella causes 1.35M infections annually in the US. Understanding its AMP resistance enables designing peptides it can't resist.","specificNumbers":"","methodology":"Study of Salmonella surface binding proteins and lipid A modifications involved in AMP resistance.","limitations":"Salmonella-specific mechanisms. Other bacteria may use different strategies."},{"rthcId":"RPEP-15467","title":"The Role of Glucagon-Like Peptide-1 Receptor Agonists in the Treatment of Cardiovascular-Kidney-Metabolic Syndrome.","authors":"Kumar, Sonal; Anderson, John E; Coviello, Andrea; Lopez-Jimenez, Francisco; Bakris, George L","year":2026,"journal":"JACC. Advances, 5(1), 102465","doi":"10.1016/j.jacadv.2025.102465","pmid":"41609289","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RAs: established cardiovascular role with proven MACE reduction, HFpEF benefits, kidney protection, and emerging PAD/AF benefits — cardiovascular standard of care beyond diabetes.","whyItMatters":"GLP-1 drugs are becoming as important for cardiology as statins. Understanding their full cardiovascular profile is essential.","specificNumbers":"","methodology":"Review of GLP-1 RA cardiovascular evidence and evolving clinical positioning.","limitations":"Short review (840 chars abstract)."},{"rthcId":"RPEP-15468","title":"Engineered N-terminal modified α/β-hybrid peptides with enhanced selectivity and stability: Multi-target antibacterials for combating MRSA.","authors":"Kumari, Jyoti; Sarkar, Aminur Rahman; Rashid, Beenish; Rathore, Arti; Firdous, Shifa; Chowdhary, Rubina; Sarkar, Biplab; Manhas, Rakshit; Rai, Rajkishor; Mahapa, Avisek","year":2026,"journal":"Bioorganic chemistry, 170, 109495","doi":"10.1016/j.bioorg.2026.109495","pmid":"41579814","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"N-terminal modified α/β-hybrid peptides: enhanced cancer vs normal cell selectivity + maintained antimicrobial activity through backbone engineering.","whyItMatters":"Selectivity is the key challenge for peptide therapeutics. Engineering backbone chemistry to enhance cancer selectivity enables safer dual-function drugs.","specificNumbers":"","methodology":"Design and synthesis of α/β-hybrid peptides with N-terminal modifications, selectivity testing (cancer vs normal cells), and antimicrobial activity assessment.","limitations":"In vitro selectivity. In vivo validation needed."},{"rthcId":"RPEP-15469","title":"Safety and Tolerability of Glucagon-Like Peptide-1 Receptor Agonists: A State-of-the-Art Narrative Review.","authors":"Kunutsor, Setor K; Seidu, Samuel","year":2026,"journal":"Drugs, 86(1), 11-36","doi":"10.1007/s40265-025-02263-0","pmid":"41351656","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Comprehensive GLP-1 RA safety review: GI (common, manageable), pancreatitis (monitoring), thyroid (reassuring), NAION (low absolute risk), bile duct (investigating), mental health (safe), musculoskeletal (variable). Evidence-based management for each.","whyItMatters":"The most comprehensive GLP-1 safety review to date — essential reading for every prescriber.","specificNumbers":"","methodology":"State-of-the-art safety review of all GLP-1 RA adverse effects and emerging safety signals with evidence-based risk management.","limitations":"Comprehensive review. Some emerging signals have limited data."},{"rthcId":"RPEP-15470","title":"Challenges and opportunities beyond antibody-drug conjugates: Toward a new era of programmable therapeutic proteins.","authors":"Kurtova, Anastasia I; Iureva, Anna M; Esetov, Nikolay S; Sokol, Daniil V; Fedotova, Polina A; Shipunova, Victoria O","year":2026,"journal":"Biochemical and biophysical research communications, 794, 153018","doi":"10.1016/j.bbrc.2025.153018","pmid":"41297517","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"PDCs, SMDCs, and novel conjugate modalities are emerging as ADC alternatives with advantages in tumor penetration, manufacturing simplicity, cost, and immunogenicity for targeted cancer therapy.","whyItMatters":"ADCs have transformed cancer therapy but are expensive and imperfect. Alternative conjugates could democratize targeted therapy.","specificNumbers":"","methodology":"Review of conjugate drug modalities beyond ADCs, covering PDCs, SMDCs, and novel platforms.","limitations":"Many alternative conjugates are still preclinical. Head-to-head comparisons with ADCs limited."},{"rthcId":"RPEP-15471","title":"Peptide-Functionalized Iron Oxide Nanoparticles for Cancer Therapy: Targeting Strategies, Mechanisms, and Translational Opportunities.","authors":"Kuskov, Andrey N; Thrapsanioti, Lydia-Nefeli; Kukovyakina, Ekaterina; Yagolovich, Anne; Vlaskina, Elizaveta; Tzanakakis, Petros; Berdiaki, Aikaterini; Nikitovic, Dragana","year":2026,"journal":"Molecules (Basel, Switzerland), 31(2)","doi":"10.3390/molecules31020236","pmid":"41599290","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Peptide-functionalized iron oxide NPs: multi-modal cancer therapy combining magnetic targeting, drug delivery, MRI imaging, and hyperthermia through peptide-guided tumor specificity.","whyItMatters":"Multi-modal cancer therapy from a single platform — diagnose, target, and treat with one nanoparticle system.","specificNumbers":"","methodology":"Review of peptide-functionalized iron oxide nanoparticle targeting strategies and multi-modal cancer therapy applications.","limitations":"Most applications preclinical. Iron oxide NP regulatory approval complex."},{"rthcId":"RPEP-15472","title":"Improvement of Chronic Spontaneous Urticaria After Glucagon-Like Peptide 1 Receptor Agonist Therapy: Report of Two Cases.","authors":"Kwiek, Bartłomiej; Sieczych, Julia; Łukowska, Katarzyna; Ambroziak, Marcin","year":2026,"journal":"Dermatology and therapy, 16(2), 1419-1425","doi":"10.1007/s13555-025-01640-7","pmid":"41535531","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RA treatment associated with CSU improvement, suggesting immunomodulatory effects on mast cell-driven inflammation and immune dysregulation beyond metabolic benefits.","whyItMatters":"CSU affects 1-2% of the population with limited treatment options. GLP-1 drugs could provide a new therapeutic approach.","specificNumbers":"","methodology":"Documentation of CSU improvement during GLP-1 RA treatment with immunomodulatory mechanism discussion.","limitations":"Case-level evidence. Cannot prove causation. Mechanism speculative."},{"rthcId":"RPEP-15473","title":"Development of an Optimized CXCR4-Targeting Theranostic Pair.","authors":"Kwon, Daniel; Bloise, Ingrid; Zhang, Zhengxing; Colpo, Nadine; Wilson, Ryan; Tan, Ruiyan; Merkens, Helen; Zeisler, Jutta; Lau, Joseph; Lin, Kuo-Shyan; Bénard, François","year":2026,"journal":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","doi":"10.2967/jnumed.125.269933","pmid":"41611474","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Optimized CXCR4-targeting peptide theranostic pair: improved tumor uptake and imaging quality for diagnostic PET + therapeutic radionuclide delivery in CXCR4-expressing cancers.","whyItMatters":"The same peptide that finds cancer on a scan can deliver radiation to kill it — precision therapy guided by precision diagnosis.","specificNumbers":"","methodology":"Peptide optimization for CXCR4 targeting, dual labeling for PET imaging and therapeutic radionuclide, biodistribution, and imaging studies.","limitations":"Preclinical optimization. Clinical translation pathway needed."},{"rthcId":"RPEP-15474","title":"Antiobesity medications in rheumatology. Quo vadis?","authors":"Kyriazi, Niki; Vassilakis, Konstantinos D; Bakiri, Amalia; Iliopoulos, Alexios; Fragoulis, George E","year":2026,"journal":"Annals of the rheumatic diseases, 85(3), 412-416","doi":"10.1016/j.ard.2025.08.013","pmid":"40946026","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RAs for rheumatic diseases: weight reduction + immunomodulation could improve disease activity, joint outcomes, and drug effectiveness in RA, PsA, OA, and gout.","whyItMatters":"Most rheumatic disease patients are overweight, worsening their condition. GLP-1 drugs could treat both obesity and the underlying inflammatory disease.","specificNumbers":"","methodology":"Review of anti-obesity medication potential in rheumatic diseases, focusing on GLP-1 RAs.","limitations":"Limited rheumatology-specific evidence. Most data extrapolated from metabolic trials."},{"rthcId":"RPEP-15475","title":"Self-assemblies from prodrugs composed of antimicrobial peptides: a revolution in local lung cancer treatment, with microbiota as a main actor.","authors":"Ladaycia, Abdallah; Lemaire, Laurent; Pailhoriès, Hélène; Lautram, Nolwenn; Franconi, Florence; Pigeon, Pascal; Jaouen, Gérard; Passirani, Catherine; Lepeltier, Elise","year":2026,"journal":"Drug delivery and translational research","doi":"10.1007/s13346-025-02037-x","pmid":"41501309","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Self-assembling AMP prodrugs: spontaneous nanostructure formation providing stability, targeting, and controlled release without carrier materials — carrier-free AMP delivery revolution.","whyItMatters":"AMP delivery is the biggest barrier to clinical use. Self-assembling prodrugs eliminate the carrier — the AMP IS the delivery system.","specificNumbers":"","methodology":"Review of self-assembling AMP prodrug design, nanostructure formation, and therapeutic applications.","limitations":"Emerging field. Many designs still preclinical."},{"rthcId":"RPEP-15476","title":"Impact of oral semaglutide on quality of life and metabolic parameters in patients with type 2 diabetes mellitus: A multicenter observational study.","authors":"Lago Garma, Javier; Gil Mouce, Cristina; Rodríguez Novo, Nazareth; Díaz Trastoy, Olaia; Santamaría Nieto, Alicia; Pérez Castro, Patricia; Díaz Ortega, Carmen; Fernández Rodríguez, Eva; Palmeiro Carballeira, Regina; Pinal Osorio, Iria; Prieto Tenreiro, Alma; Sánchez Sobrino, Paula; Tejera Pérez, Cristina; Pita Gutiérrez, Francisco; Villar Taibo, Rocío; Vidal Casariego, Alfonso","year":2026,"journal":"Endocrinologia, diabetes y nutricion, 501713","doi":"10.1016/j.endien.2026.501713","pmid":"41651756","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Oral semaglutide: improved QoL alongside HbA1c, weight, and lipid improvements in real-world T2D patients — clinical and patient-centered benefits from daily pill.","whyItMatters":"Patient quality of life is as important as lab numbers. Showing oral semaglutide improves both supports its use as a patient-centered therapy.","specificNumbers":"","methodology":"Real-world assessment of oral semaglutide effects on quality of life and metabolic parameters in T2D patients.","limitations":"Real-world observational. QoL improvements may partly reflect weight loss satisfaction."},{"rthcId":"RPEP-15477","title":"Peptides derived from exocrine secretions of venomous animals used as traditional Chinese \"worm\" medicines.","authors":"Lai, Shian; Chai, Jinwei; Luo, Yongtao; Luo, Lei; Xu, Xueqing","year":2026,"journal":"Zoological research, 47(1), 233-249","doi":"10.24272/j.issn.2095-8137.2025.509","pmid":"41633937","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Traditional medicine venom peptides are being scientifically validated: confirmed anti-inflammatory, analgesic, anticancer, and antimicrobial activities bridging ancient practice with modern pharmacology.","whyItMatters":"Traditional medicine represents centuries of human experimentation. Scientifically validating venom peptides accelerates drug discovery.","specificNumbers":"","methodology":"Review of peptides from venomous animal secretions used in traditional medicine, with scientific evidence for claimed bioactivities.","limitations":"Review. Traditional preparation methods may affect peptide activity. Dose/safety data from traditional use is imprecise."},{"rthcId":"RPEP-15478","title":"Immune-mediated necrotising myopathy following semaglutide treatment: a contributing factor?","authors":"Lam, Brian; Tiniakou, Eleni; Zhang, Xinhai Robert; Assassi, Shervin","year":2026,"journal":"BMJ case reports, 19(3)","doi":"10.1136/bcr-2025-269690","pmid":"41786442","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"IMNM (immune-mediated necrotizing myopathy) following semaglutide — rare autoimmune muscle adverse event requiring clinical awareness for unexplained weakness during GLP-1 therapy.","whyItMatters":"Rare autoimmune events with widely prescribed drugs must be documented. Muscle weakness on GLP-1 drugs should trigger IMNM consideration.","specificNumbers":"","methodology":"Case report of IMNM developing after semaglutide initiation, with clinical documentation and immunological workup.","limitations":"Single case. Cannot prove causation. IMNM has multiple triggers."},{"rthcId":"RPEP-15479","title":"Effectiveness and safety of GLP-1 receptor agonists in craniopharyngioma patients with obesity: A multicentre real-world study.","authors":"Lambert, Flora; Guillon, Emilie; Gatta-Cherifi, Blandine; Soula, Hedi; Poitou, Christine; Faucher, Pauline","year":2026,"journal":"Diabetes, obesity & metabolism, 28(1), 443-451","doi":"10.1111/dom.70216","pmid":"41153084","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RAs: effective and safe for hypothalamic obesity in craniopharyngioma patients, addressing a condition with essentially no prior effective treatments.","whyItMatters":"Craniopharyngioma obesity devastates quality of life with no effective treatment. GLP-1 drugs could be transformative for these patients.","specificNumbers":"","methodology":"Study evaluating GLP-1 RA effectiveness and safety in craniopharyngioma patients with hypothalamic obesity.","limitations":"Rare condition limits sample sizes."},{"rthcId":"RPEP-15480","title":"Neuropeptide SP protects against colitis and linked anxiety-like behavior through the putative roles of gut microbiota and metabolite inositol.","authors":"Lan, Jing; Wang, Jiaqi; Huang, Sijuan; Li, Chenyu; Deng, Ziteng; Hao, Zhihui; Ma, Yunfei","year":2026,"journal":"Nature communications, 17(1), 295","doi":"10.1038/s41467-025-67904-0","pmid":"41507168","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"SP protected against colitis and anxiety-like behavior through gut-brain axis modulation, challenging its traditional pro-inflammatory characterization and revealing protective roles in IBD.","whyItMatters":"IBD patients frequently suffer from anxiety/depression. A neuropeptide protecting against both gut inflammation and anxiety addresses the gut-brain connection.","specificNumbers":"","methodology":"Colitis model with SP pathway investigation, assessment of intestinal inflammation and anxiety-like behavior.","limitations":"Preclinical colitis model."},{"rthcId":"RPEP-15481","title":"Prolonged Release of IL-10 From Enzyme-Mediated Poly-l-(Tyrosine-co-Phenylalanine) Nanocrystals Enhances Stability and Modulates Inflammatory Responses.","authors":"Landa-Tencle, Fátima; Hernández-Valencia, Carmen G; Guzmán-Lagunes, Fernando; Montiel, Carmina; Cuellar-Entenza, Yoan; Guerrero-Sánchez, Carlos; Stumpf, Steffi; Hoeppener, Stephanie; Schubert, Ulrich S; Zamudio-Cuevas, Yessica; Sánchez-Sánchez, Roberto; Gimeno, Miquel","year":2026,"journal":"Biopolymers, 117(2), e70083","doi":"10.1002/bip.70083","pmid":"41631664","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Enzyme-mediated poly(Tyr-co-Phe) hydrogel: prolonged IL-10 release for sustained anti-inflammatory immune modulation from a biodegradable amino acid-based material.","whyItMatters":"Sustained anti-inflammatory therapy without repeated dosing could transform treatment of chronic inflammatory conditions.","specificNumbers":"","methodology":"Synthesis of poly(Tyr-co-Phe) hydrogel, IL-10 loading, enzyme-responsive release characterization, and anti-inflammatory assessment.","limitations":"In vitro release characterization. In vivo anti-inflammatory efficacy needs assessment."},{"rthcId":"RPEP-15482","title":"Obesity medications and acquired hypothalamic obesity in adults: A two-case experience.","authors":"Lang, Henry; Dorand, Madisen F; Hassan, Mahnooor; Richards, Jesse R","year":2026,"journal":"Obesity pillars, 17, 100246","doi":"10.1016/j.obpill.2026.100246","pmid":"41624164","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Two adults with acquired hypothalamic obesity achieved significant weight loss with GLP-1 drug therapy, demonstrating non-hypothalamic weight loss mechanisms for treatment-resistant obesity.","whyItMatters":"Hypothalamic obesity is devastating and untreatable. Two successful cases suggest GLP-1 drugs could help.","specificNumbers":"","methodology":"Two-case experience of obesity medications including GLP-1 drugs in adults with acquired hypothalamic obesity.","limitations":"Only two cases. Cannot generalize. Small signal."},{"rthcId":"RPEP-15483","title":"Future Perspectives on the Application of Systems Biology and Generative Artificial Intelligence in the Design of Immunogenic Peptides for Vaccines.","authors":"Lastra, José M Pérez de la; Sobrino, Isidro; Rodríguez Borges, Víctor M; de la Fuente, José","year":2026,"journal":"Vaccines, 14(2)","doi":"10.3390/vaccines14020177","pmid":"41746097","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Systems biology + generative AI integration: enables multi-scale bacterial vulnerability analysis, de novo AMP design with predicted activity, and pre-synthesis resistance prediction for next-generation antimicrobials.","whyItMatters":"Current AMP discovery is piecemeal. Integrating systems biology with AI could produce comprehensive, resistance-proof antimicrobials designed from first principles.","specificNumbers":"","methodology":"Perspective on future applications of systems biology and generative AI for AMP discovery and design.","limitations":"Future-focused perspective. Many proposed integrations not yet demonstrated."},{"rthcId":"RPEP-15484","title":"Effect of Glucagon-like Peptide-1 Receptor Agonists on Outcomes and Complications Following Arthroscopic Rotator Cuff Repair: A Matched-Cohort Analysis.","authors":"Lauck, Bradley J; Colson, Charles B; Bank, Nicholas C; Trasolini, Nicholas A; Waterman, Brian R; Churchill, Jessica; Reynolds, Alan W","year":2026,"journal":"Orthopaedic journal of sports medicine, 14(2), 23259671251412408","doi":"10.1177/23259671251412408","pmid":"41660290","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 RA: improved outcomes and reduced complications after elective abdominal surgery, extending perioperative benefits to this common surgical category.","whyItMatters":"Abdominal surgery is one of the most common surgical categories. GLP-1 drugs improving outcomes would affect millions of patients.","specificNumbers":"","methodology":"Study evaluating GLP-1 RA effects on outcomes and complications following elective abdominal surgery.","limitations":"Observational. Cannot prove causation. Aspiration risk remains a separate consideration."},{"rthcId":"RPEP-15485","title":"Determination of the structure and dynamics of linear polypeptide gramicidin A at atomic-scale resolution.","authors":"Laxmi Pradhan, Bijay; Sen, Prince; Kumar, Adarsh; Bhunia, Anirban; Kishor Dey, Krishna; Ghosh, Manasi","year":2026,"journal":"RSC advances, 16(9), 8072-8104","doi":"10.1039/d5ra09180b","pmid":"41675194","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15486","title":"Lactic Acid Bacteria-derived Bacteriocins: A Promising Antimicrobial Strategy against Multidrug-resistant for Neonatal Sepsis Pathogens.","authors":"Laxmi, Vijay; Verma, Sheetal; Kumar, Manoj; Venkatesh, Vimala; Mohit; Maury, Jayhind; Mohd, Shayan; Tripathi, Shalini","year":2026,"journal":"Probiotics and antimicrobial proteins","doi":"10.1007/s12602-026-10934-x","pmid":"41656481","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies LAB-derived bacteriocins as promising antimicrobial agents against MDR neonatal sepsis pathogens, with several key advantages: narrow-spectrum activity that spares beneficial microbiota, biocompatibility particularly important for immunocompromised newborns, and favorable physicochemical properties including thermal stability, enzymatic resistance, and pH tolerance. Milk-derived LAB strains are highlighted as particularly relevant given breast milk's natural protective functions for newborns. Current evidence is primarily in vitro, with clinical trials needed.","whyItMatters":"Neonatal sepsis is a leading cause of newborn death worldwide, and antibiotic resistance is making it harder to treat. Newborns are uniquely vulnerable because their immune systems are immature and their microbiomes are still developing. Bacteriocins from milk-associated bacteria could provide a natural, microbiome-friendly antimicrobial strategy — potentially as supplements, topical agents, or adjuncts to antibiotics in NICUs.","specificNumbers":"","methodology":"Narrative review compiling current literature on LAB-derived bacteriocins, covering their in vitro antimicrobial activity against MDR neonatal sepsis pathogens, molecular diversity, mechanisms of action, physicochemical properties, and clinical potential.","limitations":"The evidence is almost entirely in vitro — no clinical trials of bacteriocins for neonatal sepsis have been reported. Production scale-up and pharmaceutical formulation challenges are acknowledged but not solved. Narrow-spectrum activity, while beneficial for the microbiome, could be a limitation if the causative pathogen isn't identified quickly. Regulatory pathways for peptide-based antimicrobials in neonates are unclear. The review may overstate readiness for clinical application given the early stage of research."},{"rthcId":"RPEP-15487","title":"Real-World Outcomes of [177Lu]Lu-DOTA-TATE Peptide Receptor Radionuclide Therapy in Patients with Metastatic Gastroenteropancreatic Neuroendocrine Tumors: Data from a Belgian ENETS Center of Excellence.","authors":"Lazarenko, I; Mileva, M; Manta, R; Kristanto, P; Hendlisz, A; Van Laethem, J L; Wimana, Z; Artigas, C; Flamen, P; Karfis, I","year":2026,"journal":"Acta gastro-enterologica Belgica, 89(1), 13-24","doi":"10.51821/89.1.14882","pmid":"41745634","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15488","title":"Structural determinants of glycosaminoglycan oligosaccharides as LL-37 inhibitors in breast cancer.","authors":"Le Fournis, Chloe; Maszota-Zieleniak, Martyna; Kulesza, Adam; Chopra, Pradeep; Boons, Geert-Jan; Aubrey, Nicolas; Liesecke, Franziska; Samsonov, Sergey A; Weber, Günther","year":2026,"journal":"Glycobiology, 36(4)","doi":"10.1093/glycob/cwag010","pmid":"41674152","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15489","title":"A treat-to-target approach for obesity management: A post hoc analysis of the SURMOUNT-5 trial.","authors":"le Roux, Carel W; Busetto, Luca; Aronne, Louis; Horn, Deborah Bade; Dimitriadis, Georgios K; Falcon, Beverly; Garcia-Perez, Luis-Emilio; Valderas, Elisa Gomez; Gibble, Theresa Hunter; Senyucel, Cagri; Dunn, Julia P","year":2026,"journal":"Diabetes, obesity & metabolism","doi":"10.1111/dom.70531","pmid":"41635114","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In SURMOUNT-5 at 72 weeks, 23.1%-33.9% of tirzepatide-treated participants reached proposed treat-to-target (TtT) thresholds compared to 14.2%-20.7% with semaglutide. Those reaching targets had greater weight reduction than the overall population.\n\nAmong participants reaching a waist-to-height ratio (WHtR) <0.53, 77% achieved low disease activity to remission (meeting goals for at least 4 of 5 defined cardiometabolic risk parameters), with an odds ratio of 2.31 (p<0.001) compared to those not reaching this target. The BMI threshold was not statistically associated with quality of life outcomes (SF-36v2 physical component score).","whyItMatters":"Obesity medicine has lacked clear treatment targets — unlike diabetes (HbA1c goals) or hypertension (blood pressure targets). This analysis introduces a treat-to-target framework where specific body composition metrics predict cardiometabolic health outcomes. Finding that waist-to-height ratio is a better predictor than BMI alone could shift how obesity treatment success is measured, and the data show tirzepatide helps more patients reach these meaningful targets than semaglutide.","specificNumbers":"","methodology":"Post hoc analysis of the SURMOUNT-5 randomized trial comparing tirzepatide to semaglutide in participants with obesity over 72 weeks. Researchers evaluated the proportion reaching proposed TtT thresholds for waist-to-height ratio and BMI, then assessed associations between meeting these thresholds and achieving low disease activity to remission (defined by meeting ≥4 of 5 cardiometabolic risk parameters) and quality of life improvements (SF-36v2 physical component score).","limitations":"This is a post hoc analysis, not a pre-specified trial endpoint, so results are hypothesis-generating. The TtT thresholds are proposed but not yet validated prospectively. The analysis cannot establish that reaching thresholds caused the cardiometabolic improvements (rather than being correlated). BMI-based targets were not associated with quality of life outcomes, limiting their utility. The trial population may not represent all patients with obesity."},{"rthcId":"RPEP-15490","title":"Comparative effectiveness of tirzepatide and semaglutide for obesity management in US clinical practice: a 6-month retrospective cohort study.","authors":"le Roux, Carel W; Done, Nicolae; Brnabic, Alan J M; Zion, Abigail; Lipkovich, Ilya; Kadziola, Zbigniew; Dunn, Julia P; Desai, Urvi; Kirson, Noam; Dimitriadis, Georgios K; Kan, Hong","year":2026,"journal":"Journal of endocrinological investigation, 49(2), 413-423","doi":"10.1007/s40618-025-02792-1","pmid":"41661445","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15491","title":"Survodutide for treatment of obesity: Baseline characteristics of participants in a randomized, double-blind, placebo-controlled, phase 3 trial (SYNCHRONIZE™-1).","authors":"le Roux, Carel W; Wharton, Sean; Bozkurt, Biykem; Platz, Elke; Bleckert, Gabriele; Ajaz Hussain, Samina; Brueckmann, Martina; Startseva, Elena; Kloer, Isabel M; Kaplan, Lee M","year":2026,"journal":"Diabetes, obesity & metabolism, 28(1), 337-346","doi":"10.1111/dom.70196","pmid":"41187967","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The SYNCHRONIZE-1 trial baseline characteristics (n=725 from 14 countries):\n\n- Mean age: 47.1 years; 59.4% female\n- Mean BMI: 37.9 kg/m²; mean waist circumference: 115.2 cm\n- Geographic distribution: 47.3% North America, 21.0% Europe, 20.0% East Asia\n- Obesity complications: hypertension (40.0%), dyslipidaemia (33.7%), prediabetes (30.2%)\n- Mean HbA1c: 5.5%, eGFR: 93.0 mL/min/1.73 m², SBP/DBP: 127.0/82.7 mmHg\n- Mean LDL cholesterol: 116.4 mg/dL; 21.8% on lipid-lowering drugs\n\nParticipants were randomized 1:1:1 to survodutide 3.6 mg, 6.0 mg, or placebo for 76 weeks. Primary endpoints are percent body weight change and achievement of ≥5% weight reduction at Week 76.","whyItMatters":"Survodutide represents a new approach to obesity treatment by combining GLP-1 and glucagon receptor activation. While GLP-1 drugs like semaglutide reduce appetite, glucagon receptor activation may additionally boost energy expenditure and fat burning. If successful, survodutide could offer even greater weight loss than current single-mechanism drugs.","specificNumbers":"","methodology":"This is a randomized, double-blind, placebo-controlled Phase 3 trial. Adults aged ≥18 with BMI ≥30 (or ≥27 with ≥1 obesity complication) without type 2 diabetes were enrolled across 14 countries. Participants were randomized 1:1:1 to weekly subcutaneous survodutide (up-titrated to 3.6 or 6.0 mg) or placebo for 76 weeks. This publication reports baseline characteristics only.","limitations":"This publication reports only baseline characteristics — no efficacy or safety results are available yet. The trial excludes people with type 2 diabetes (a separate trial covers that population). The 76-week primary endpoint will provide important data, but longer-term outcomes and maintenance effects remain unknown. Comparison to other obesity drugs will require cross-trial interpretation since this is placebo-controlled."},{"rthcId":"RPEP-15492","title":"A Dual-Model Machine Learning Framework for Interpretable Design and Ensemble Prediction of C-Amidated Antimicrobial Peptides.","authors":"Le, Dang-Huy; Zhu, Yujie; Zhang, Tianmeng; Li, Wenyi; Hung, Andrew; Houshyar, Shadi; Le, Tu C","year":2026,"journal":"ACS applied materials & interfaces","doi":"10.1021/acsami.6c00110","pmid":"41787253","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The dual-model framework (CAmidPred) successfully addressed the gap in AMP prediction for chemically modified peptides:\n\n- The Explainable Boosting Machine extracted interpretable, actionable sequence-level design rules for C-amidated AMPs — providing researchers with understandable guidelines rather than black-box predictions\n- The fine-tuned ESM2 deep learning model provided reliable deployment-grade activity classification\n- Design rules were validated against published alanine-scanning experiments, confirming the model's biological relevance\n- The framework identified a pardaxin variant with improved activity against E. coli, demonstrating practical utility for targeted AMP design\n- C-terminal amidation improves AMP structural stability, membrane interaction, and protease resistance — properties the framework accounts for","whyItMatters":"C-terminal amidation is one of the most common modifications in natural and therapeutic peptides, yet most AMP prediction tools ignore it. By building the first framework specifically for amidated peptides, this study fills a critical gap in computational peptide design. The interpretable component is especially valuable — unlike black-box AI that just gives predictions, this system explains why certain sequences work, enabling researchers to rationally design better peptides.","specificNumbers":"","methodology":"The researchers developed two complementary models: (1) an Explainable Boosting Machine (EBM) for interpretable design rule extraction from C-amidated AMP sequences, and (2) a fine-tuned ESM2 protein language model for high-accuracy activity prediction. Models were trained on datasets of C-amidated AMPs with known activity against E. coli. Design rules were cross-referenced with published alanine-scanning mutagenesis data. The framework was validated by designing and predicting activity for pardaxin variants.","limitations":"The framework was demonstrated against E. coli only — activity predictions for other pathogens would need separate models. The improved pardaxin variant was identified computationally; it's unclear from the abstract whether it was experimentally validated. The training data for C-amidated AMPs may be limited compared to general AMP databases. The framework focuses on one modification type (C-amidation) and doesn't address other common modifications like cyclization or D-amino acid substitutions."},{"rthcId":"RPEP-15493","title":"Engineering Elastin-Like Peptide-Based Nanoparticles displaying Variable Domain of the Heavy Chain of Heavy-Chain-Only Antibodies for SARS-CoV-2 Neutralization.","authors":"Le, Duc H T; van Oostrum, Jenny; van de Westerlo, Els; Wang, Jianhong; Overheul, Gijs J; van Rij, Ronald P; Leenders, William P J; Bijlsma, Jetta; Roodink, Ilse; van Hest, Jan C M; Verdurmen, Wouter P R","year":2026,"journal":"Biomacromolecules, 27(2), 1446-1458","doi":"10.1021/acs.biomac.5c02042","pmid":"41566147","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15494","title":"GLP-1s Versus DPP-4s and Risk of Dementia in Patients Requiring Hemodialysis: A Target Trial Emulation Study.","authors":"Le, Dustin; Kilpatrick, Mark; Kraft, Walter K; Grams, Morgan E; Jaar, Bernard G; Shin, Jung-Im","year":2026,"journal":"Diabetes care, 49(1), 128-136","doi":"10.2337/dc25-1836","pmid":"41232069","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15495","title":"Impact of GLP-1 receptor agonists on gastric residuals in patients receiving gastrointestinal endoscopic procedures.","authors":"Le, Kim; Prasad, Sanjay; Shah, Rajesh","year":2026,"journal":"Proceedings (Baylor University. Medical Center), 39(1), 25-28","doi":"10.1080/08998280.2025.2583025","pmid":"41487538","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 218 adults on GLP-1 receptor agonists undergoing upper endoscopy, retained gastric content (RGC) was observed in 20.6% of patients. Nine procedures were terminated prematurely due to retained content. One aspiration event and one intraprocedural intubation occurred. Despite the high prevalence of retained stomach content, the overall incidence of severe complications or adverse outcomes was low.","whyItMatters":"With millions of people now taking GLP-1 drugs like semaglutide and liraglutide, understanding their impact on routine medical procedures is critical for patient safety. GLP-1 drugs slow stomach emptying, which means standard fasting instructions before endoscopy may not be sufficient. This data helps gastroenterologists and anesthesiologists plan safer procedures for this growing patient population.","specificNumbers":"","methodology":"Retrospective cohort study of 218 adults taking GLP-1 receptor agonists who underwent esophagogastroduodenoscopy (upper endoscopy) between June 2013 and June 2023 at Baylor Scott & White Health system. Researchers analyzed the frequency of retained gastric content and related adverse events.","limitations":"This was a retrospective study at a single health system, which may limit generalizability. There was no control group of non-GLP-1 users for direct comparison of RGC rates. The study did not differentiate between specific GLP-1 drugs or doses, and did not assess whether patients followed modified fasting protocols. The 10-year time span means practice patterns and available drugs changed during the study period."},{"rthcId":"RPEP-15496","title":"Isobavachalcone reduces blood glucose and promotes muscle development via dipeptidyl peptidase-4 inhibition.","authors":"Lee, Eun Ju; Shaikh, Sibhghatulla; Ahmad, Khurshid; Lee, Si Han; Choi, Jae-Moon; Lee, Yong Ho; Choi, Inho","year":2026,"journal":"International journal of biological macromolecules, 339(Pt 1), 149858","doi":"10.1016/j.ijbiomac.2025.149858","pmid":"41443458","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Out of 241 flavonoid compounds screened computationally, isobavachalcone (IBC) showed the highest binding energy to DPP-4 and the lowest IC50 value, making it the most potent inhibitor identified. In Caco-2 intestinal cells, IBC reduced DPP4 mRNA and protein expression.\n\nIn mice on a high-fat diet, IBC reduced hyperglycemia more effectively than sitagliptin by increasing circulating GLP-1 and insulin levels. IBC also decreased DPP-4 activity and expression while increasing GLUT2 expression in the liver and GLUT4 expression in muscles — both critical glucose transporters. Additionally, IBC promoted human skeletal muscle cell proliferation and differentiation, indicating potential benefits for diabetes-related muscle atrophy.","whyItMatters":"Millions of people take DPP-4 inhibitors for type 2 diabetes, but these synthetic drugs can cause side effects. Finding a natural compound that works even better could eventually lead to safer, plant-derived diabetes treatments. The added muscle-building benefit is particularly notable since muscle loss is a common and underappreciated complication of type 2 diabetes.","specificNumbers":"","methodology":"The study used a three-tier approach: (1) computational screening of 241 flavonoid compounds using molecular docking to identify potential DPP-4 inhibitors, (2) in vitro testing in Caco-2 intestinal cells to confirm DPP-4 inhibition and measure IC50 values, and (3) in vivo testing in mice fed a high-fat diet to assess blood sugar control, GLP-1 levels, insulin levels, and glucose transporter expression. Muscle cell effects were tested separately using human skeletal muscle cells.","limitations":"The in vivo results are from mice on a high-fat diet, which is a model for type 2 diabetes but not identical to human disease. The study did not test long-term safety or toxicity of IBC. Bioavailability of IBC in humans is unknown — compounds that work in mice may not absorb well or reach effective concentrations in people. No human clinical trials have been conducted. The muscle growth effects were observed in cell cultures, not in animals or humans."},{"rthcId":"RPEP-15497","title":"Peptide-based antimicrobial effect against carbapenem-resistant Acinetobacter baumannii: preclinical drug assessment and translational potential.","authors":"Lee, Hak Jun; Lee, Seung Jun; Sung, Yoon Hyun; Park, Seung Min; Choi, Seung Pyo; Kim, Yangmee; Yoon, Young Kyung","year":2026,"journal":"Frontiers in pharmacology, 17, 1732644","doi":"10.3389/fphar.2026.1732644","pmid":"41788804","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15498","title":"Real-World Insights into Dual Calcitonin Gene-Related Peptide (CGRP) Therapies for Chronic Migraine: A Retrospective Review.","authors":"Lee, Ho Hyun; Cheung, Anita J; Lee, Anson Y; Jahansooz, Julia R; Weldon, Edward J; Ishikawa, Kyle M; Yoshioka, Reyn; Woo, Man Ian; Liquard, Lana; Kim, Eonjung Angeline; Carrazana, Enrique; Liow, Kore K","year":2026,"journal":"Pain physician, 29(1), 75-82","doi":null,"pmid":"41628212","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 90 chronic migraine patients (27 on dual CGRP therapy, 63 on mono therapy):\n- Dual therapy reduced headache severity by 20% vs 10% with mono therapy (p = 0.039)\n- Dual therapy patients averaged 4 fewer headache days, with some experiencing up to 14 fewer days, though this did not reach statistical significance (p = 0.112)\n- No significant differences in other migraine-associated symptoms (nausea, photophobia, etc.)\n- Adverse events were mild in both groups with no serious events or discontinuations\n- Both treatment approaches used CGRP ligand-targeting antibodies combined with receptor-targeting small molecules for synergistic blockade","whyItMatters":"A significant proportion of chronic migraine patients have an inadequate response to single CGRP drugs. This is the first real-world evidence that combining two different types of CGRP-targeting medications — attacking the peptide from two angles simultaneously — can provide additional benefit without added safety risks. This dual approach could change treatment strategies for the most difficult-to-treat migraine patients.","specificNumbers":"","methodology":"Retrospective matched cohort study at a single US neurological center. 90 chronic migraine patients treated with CGRP inhibitors between May 2018 and February 2024 were analyzed. 27 patients on dual therapy (L-mAb + SMA) were matched by age and gender with 63 mono-therapy patients. Outcomes including headache frequency, duration, severity, and symptoms were compared at baseline and 3 months post-treatment.","limitations":"Small sample size (90 patients, only 27 on dual therapy) at a single center limits generalizability. Retrospective design introduces selection and confounding bias. The 3-month follow-up is relatively short. The headache frequency reduction, while clinically meaningful (up to 14 fewer days), did not reach statistical significance. Newer CGRP agents were not included. The predominantly female patient population may not represent all migraine patients."},{"rthcId":"RPEP-15499","title":"Outcomes of Maternal Periconceptional Exposure to Glucagon-Like Peptide-1 Receptor Agonists: A Scoping Review of Evidence and Reporting Trends.","authors":"Lee, In Ok; Ghiasi, Maryam; Wong, Karen; Walker, Mark","year":2026,"journal":"Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC, 48(1), 103191","doi":"10.1016/j.jogc.2025.103191","pmid":"41319953","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"From 881 screened articles, 13 met inclusion criteria: 10 case reports and 3 cohort studies examining pregnancy outcomes after periconceptional GLP-1 receptor agonist exposure.\n\nKey findings across all included studies:\n- No increased risk of major congenital malformations in any study\n- No pregnancy losses or elective terminations reported in any study\n- Minor complications reported in case reports included: emergency cesarean delivery, preeclampsia, macrosomia (large baby), shoulder dystocia, and transient neonatal hypoglycemia\n- These minor complications are common in pregnancies complicated by pre-existing diabetes and obesity","whyItMatters":"This is one of the most urgent questions in reproductive health right now. The 'Ozempic baby' phenomenon — unexpected pregnancies in women on GLP-1 drugs whose fertility was restored by weight loss — has generated widespread public concern. Women who discover they're pregnant while on these medications need evidence-based guidance about whether to be worried. This review provides early reassurance that accidental exposure does not appear to cause major birth defects, though the evidence remains limited.","specificNumbers":"","methodology":"The scoping review followed Joanna Briggs Institute methodology. Databases searched included MEDLINE, Embase, Scopus, open-access clinical trial registries, ProQuest Dissertations & Theses Global, and medRxiv, covering January 2005 to March 2025. All evidence levels and report types were included. Articles were screened in duplicate at abstract and full-text levels by two independent reviewers, with disagreements resolved through consensus. Data from 13 eligible articles were charted and summarized narratively.","limitations":"The evidence base is extremely limited — only 13 studies, predominantly case reports (10 of 13), which represent the lowest level of clinical evidence. The 3 cohort studies are not sufficient for definitive conclusions. The total number of exposed pregnancies across all studies is very small. Publication bias may favor reporting of adverse outcomes. The review cannot distinguish between effects of the drug and effects of the underlying conditions (diabetes, obesity) that prompted its use. Long-term developmental outcomes of exposed children are not available. Different GLP-1 drugs may carry different risks."},{"rthcId":"RPEP-15500","title":"Small Extracellular Vesicle-Mediated Peptide Delivery to the Mouse Corneal Endothelium In Vivo.","authors":"Lee, JeongGoo; Lee, Sun Young; Pollalis, Dimitrios; Heur, Martin","year":2026,"journal":"Ophthalmology science, 6(1), 100900","doi":"10.1016/j.xops.2025.100900","pmid":"41049108","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15501","title":"Inhalation-Based Nanoparticle Drug Delivery Targeting the Diseased Lower Airways in Idiopathic Pulmonary Fibrosis.","authors":"Lee, Jin Woong; Skibba, Melissa; Tang, Tyler; Noh, Hyeran; Brasier, Allan R; Hong, Seungpyo","year":2026,"journal":"Pharmaceutics, 18(2)","doi":"10.3390/pharmaceutics18020168","pmid":"41754911","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15502","title":"Structure-driven enhancement of anti-biofilm and anti-inflammatory activities of chimeric antimicrobial peptides against Pseudomonas aeruginosa.","authors":"Lee, Jung Ro; Lee, Jong-Kook; Meirambek, Symbat; Lee, Mina; Jang, Mi-Kyeong; Park, Seong-Cheol","year":2026,"journal":"Biochemical and biophysical research communications, 797, 153180","doi":"10.1016/j.bbrc.2025.153180","pmid":"41443046","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15503","title":"Alpha-defensins promote macrophage inflammatory activation via RNF31 signaling.","authors":"Lee, Jungnam; Mohammad, Naweed; Mun, Seyoung; Han, Kyudong; Flagg-Dowie, Tammy; Magallon, Maria; Brantly, Mark L; Serban, Karina A","year":2026,"journal":"Genes & genomics, 48(3), 455-470","doi":"10.1007/s13258-025-01735-7","pmid":"41557095","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15504","title":"Continuous positive airway pressure effects on energy expenditure, intake, hormonal regulation, and body composition: a randomized trial.","authors":"Lee, Pei-Lin; Chien, Meng-Yueh; Lai, Shang-Ru; Gooley, Joshua J; Feng, Hsin-Chun; Chen, Shih-Kuo; Lin, Ming-Tzer; Chen, Yung-Hsuan; Chiu, Hung-Chih; Liu, Po-Kang; Ku, Bo-Wen; Wang, Su-Mei; Chang, Chin-Hao; Yang, Wei-Shiung; Yu, Chong-Jen","year":2026,"journal":"Sleep, 49(1)","doi":"10.1093/sleep/zsaf259","pmid":"40874641","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15505","title":"SGLT2 Inhibitors and GLP-1 Receptor Agonists in Kidney Transplantation: A Systematic Review and Meta-Analysis.","authors":"Lee, Sul A; Verhoeff, Rucháma; Hullekes, Frank; Hansrivijit, Panupong; de Bruin, Ron W F; Porte, Robert J; Riella, Leonardo V","year":2026,"journal":"Transplantation, 110(1), e217-e228","doi":"10.1097/TP.0000000000005496","pmid":"40702593","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15506","title":"Awareness, Diagnostic Approaches, and Management of Heart Failure in Korea: A Nationwide Survey Comparing Primary Care Physicians and Cardiology Specialists.","authors":"Lee, Sunki; Kong, Min Gyu; Jung, Mi-Hyang; Kim, Hack-Lyoung; Choi, Jae Hyuk; Na, Jin Oh; Cho, Yang Hyun; Choi, Dong-Ju; Kim, Eung Ju","year":2026,"journal":"International journal of heart failure, 8(1), 76-88","doi":"10.36628/ijhf.2025.0123","pmid":"41696055","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15507","title":"GLP-1 receptor agonists reduce dementia and Alzheimer disease risk in diabetic Patients with CKD.","authors":"Lee, Wen-Teng; Wang, Jing Tong; Tsai, Ming-Hsien; Fang, Yu-Wei","year":2026,"journal":"Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association","doi":"10.1093/ndt/gfag032","pmid":"41697144","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15508","title":"Effects of GLP-1 receptor agonists on copeptin in euvolemic participants.","authors":"Leibnitz, Svenja; Winzeler, Bettina; Refardt, Julie; Vogt, Deborah R; Sailer, Clara O; Christ-Crain, Mirjam","year":2026,"journal":"European journal of endocrinology, 194(2), 91-101","doi":"10.1093/ejendo/lvag005","pmid":"41525326","tags":[],"studyType":"secondary-analysis-rct","evidenceStrength":"high","keyFinding":"Three weeks of treatment with the GLP-1 receptor agonist dulaglutide significantly suppressed copeptin levels — a stable surrogate marker for vasopressin (the antidiuretic hormone) — by 12% compared to placebo in euvolemic participants.\n\nThe median within-subject copeptin difference was -0.7 pmol/L (p=0.047). This suppression was independent of dulaglutide's effects on blood pressure, BMI, or nausea incidence, suggesting a direct effect of GLP-1 signaling on the vasopressin system rather than a secondary consequence of other GLP-1 actions.\n\nThis is the first evidence that GLP-1 receptor agonists directly inhibit the vasopressin system, offering a physiological explanation for why GLP-1 drugs reduce fluid intake and urine output.","whyItMatters":"GLP-1 drugs are known to affect fluid balance — patients often drink less and urinate less — but the mechanism was unknown. This study provides the first direct link between GLP-1 signaling and vasopressin suppression, explaining a physiological effect that affects millions of people taking these drugs. It also opens new therapeutic possibilities for conditions involving vasopressin dysregulation, like primary polydipsia.","specificNumbers":"n=54 · 34 polydipsia patients + 20 healthy · 12% copeptin reduction · -0.7 pmol/L difference · p=0.047 · 3-week treatment · Dulaglutide 1.5 mg weekly","methodology":"Secondary analysis of two randomized, double-blind, placebo-controlled crossover trials. Fifty-four participants (34 with primary polydipsia, 20 healthy) received 3 weeks of dulaglutide 1.5 mg or placebo subcutaneously once weekly, with blood drawn at 08:00 after each treatment phase. Within-subject copeptin differences were analyzed using the Wilcoxon rank test.","limitations":"This is a secondary analysis — the original trials were not designed to assess vasopressin effects. The sample size of 54 is modest, and the 3-week duration may not capture long-term effects. The p-value of 0.047 is borderline significant. Participants were young (median age 27), lean (median BMI 23), and predominantly female (63%), limiting generalizability to older or obese populations typical of GLP-1 drug users."},{"rthcId":"RPEP-15509","title":"An effective tumor-inhibiting siRNA delivery platform.","authors":"Leng, Qixin; Mixson, A James","year":2026,"journal":"Biochemical and biophysical research communications, 807, 153430","doi":"10.1016/j.bbrc.2026.153430","pmid":"41691982","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15510","title":"Overcoming Ligand Discovery Challenges: Developing Peptide-Based Tracers for SPSB2.","authors":"Lenz, Christopher; Elson, Lewis; Dopfer, Johannes; Farges, Frederic; Krämer, Andreas; Löhr, Frank; Müller, Susanne; Guéret, Stéphanie M; Waldmann, Herbert; Dötsch, Volker; Saxena, Krishna; Knapp, Stefan","year":2026,"journal":"ACS chemical biology, 21(2), 274-283","doi":"10.1021/acschembio.5c00702","pmid":"41358868","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Researchers developed peptide-based tracers for the E3 ligase SPSB2, a key component in designing PROTAC degrader drugs. Degron peptide sequences recognized by SPSB2 were conjugated with cell-penetrating peptides (CPPs) to achieve cellular delivery. A high-resolution crystal structure was obtained, and biophysical techniques confirmed binding. Confocal microscopy and BRET-based assays demonstrated successful cellular delivery and potent target engagement. This provides a blueprint for developing peptide-based tools to evaluate new E3 ligase targets for PROTAC drug design.","whyItMatters":"PROTACs are among the most exciting new drug modalities — they hijack the cell's protein disposal system to destroy disease-causing proteins. But designing PROTACs requires new E3 ligase ligands, and many potential ligands based on natural degron peptides can't enter cells. This study solves that delivery problem using cell-penetrating peptides, expanding the toolkit for PROTAC drug development and potentially enabling a new generation of targeted protein degradation therapies.","specificNumbers":"High-resolution crystal structure obtained · multiple CPP conjugates tested · BRET-based cellular TE assays · confocal microscopy delivery confirmation · SPSB2 E3 ligase targeted","methodology":"Degron peptide sequences for SPSB2 were conjugated with various polycationic cell-penetrating peptides. A crystal structure of the SPSB2-degron complex was determined. Biophysical techniques assessed how each modification affected binding. Cellular delivery was confirmed by confocal microscopy, and target engagement was measured using BRET-based assays in living cells.","limitations":"This is a proof-of-concept study for target engagement methodology rather than a therapeutic study. The SPSB2 system served as a model; applicability to other E3 ligases needs validation. The CPP-degron conjugates were used as research tools, not as therapeutic candidates. In vivo delivery and pharmacokinetics of the peptide conjugates were not assessed."},{"rthcId":"RPEP-15511","title":"Incretin Mimetics in Cancer and Cardiovascular Disease: JACC: CardioOncology State-of-the-Art Review.","authors":"Leong, Darryl; Gong, Selena; Sattar, Naveed; Narayan, Vivek; Reizine, Natalie M; Gerstein, Hertzel; Vellky, Jordan","year":2026,"journal":"JACC. CardioOncology, 8(1), 1-16","doi":"10.1016/j.jaccao.2025.12.003","pmid":"41705747","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15512","title":"Recurrent bilateral brachial plexus neuritis following rapid semaglutide-induced weight loss: a case report.","authors":"Lesinszki, Lukács S; Khalili, Radmanesh; Jiang, Haiyang; Jha, Shivangi; Bernad, Peter G","year":2026,"journal":"BMC neurology, 26(1), 123","doi":"10.1186/s12883-026-04664-4","pmid":"41588354","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The patient, a 39-year-old man with a prior episode of unilateral brachial neuritis, developed recurrent bilateral upper limb weakness following a 70-pound weight loss over 8 months on semaglutide. Specific deficits included bilateral radial sensory loss, finger extensor paralysis, right triceps weakness, and decreased left grip strength.\n\nCorticosteroids provided pain relief but motor and sensory deficits persisted despite physiotherapy. This represents the first reported case linking semaglutide use with brachial plexus neuritis (Parsonage-Turner syndrome).","whyItMatters":"Semaglutide is used by millions of people for diabetes and weight loss. As its use expands, identifying rare but serious side effects is critical. This case suggests that rapid weight loss — whether caused by the drug directly or through nutritional deficiency — may trigger nerve damage in susceptible individuals. It's the first reported case linking semaglutide to brachial plexus neuritis.","specificNumbers":"","methodology":"This is a clinical case report documenting a single patient's experience. The diagnosis was based on clinical examination, patient history, and standard neurological assessment. The temporal association between semaglutide use, rapid weight loss, and symptom onset was noted.","limitations":"This is a single case report, which is the weakest form of clinical evidence. It can establish a temporal association but cannot prove that semaglutide or the weight loss it caused directly triggered the nerve damage. The patient had a prior history of brachial neuritis, making him predisposed. The exact mechanism — whether related to the drug itself, rapid weight loss, nutritional deficiency, or coincidence — cannot be determined from one case."},{"rthcId":"RPEP-15513","title":"Prescribing Trends in Glucagon-Like Peptide-1 Medications Among Pregnant and Postpartum Persons.","authors":"Lessard, Chloe; Cary, Caroline; In, Alexander; Steinle, Jacob; Lin, Binx Y; Kablinger, Anita S; Grucza, Richard A; Bello, Jennifer K; Galati, Bridget M; Kimmel, Mary; Bruno, Ann M; Kelly, Jeannie C; Xu, Kevin Young","year":2026,"journal":"Obstetrics and gynecology, 147(3), 290-292","doi":"10.1097/AOG.0000000000006161","pmid":"41505759","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15514","title":"Glucagon-like peptide-1 receptor agonists and Wernicke encephalopathy: A pharmacovigilance study and literature review.","authors":"Lev, Dana; Leibowitz, Avshalom; Lang, Alon; Shlomai, Gadi; Twig, Gilad; Eden-Friedman, Yehudit; Engel, Tal; Cukierman-Yaffe, Tali; Dankner, Rachel; Gerstein, Hertzel C; Goldman, Adam","year":2026,"journal":"Clinical nutrition (Edinburgh, Scotland), 57, 106571","doi":"10.1016/j.clnu.2025.106571","pmid":"41534460","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15515","title":"Migraine epidemiology, comorbidities and therapeutic landscape: a national population-based study.","authors":"Lev, Nirit; Sheffer, Lihie; Peles, Ido; Elefant, Emily; Ifergane, Gal","year":2026,"journal":"Frontiers in neurology, 17, 1743203","doi":"10.3389/fneur.2026.1743203","pmid":"41668695","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15516","title":"Non-specific Protein and Peptide Antibacterial Factors of Mammals.","authors":"Levashov, Pavel; Zaitsev, Ilia; Zaitsev, Sergei; Gasanova, Daria","year":2026,"journal":"The protein journal, 45(1), 83-99","doi":"10.1007/s10930-025-10314-4","pmid":"41553663","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15517","title":"Chronic Kidney Disease, Nutrition, and the Brain: How to Maintain Brain Health Through Nutrition in Chronic Kidney Disease.","authors":"Levassort, Hélène; Decaix, Théodore; Michon, Pierre-Louis; Pépin, Marion; Lilamand, Matthieu","year":2026,"journal":"Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation","doi":"10.1053/j.jrn.2026.01.005","pmid":"41644021","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Chronic kidney disease contributes to cognitive impairment through the gut-kidney-brain axis, with uremic toxins (amplified by gut dysbiosis) damaging the blood-brain barrier, reducing neurogenesis, and promoting neuroinflammation. The review proposes an integrated approach combining plant-based diets (Mediterranean, DASH), physical activity, and pharmacological therapies including GLP-1 receptor agonists and SGLT2 inhibitors for synergistic protection of both kidney and brain function.","whyItMatters":"CKD affects over 800 million people worldwide, and cognitive impairment is an increasingly recognized but underaddressed complication. The gut-kidney-brain axis framework provides a mechanistic link between kidney disease and brain damage, opening new therapeutic avenues. The inclusion of GLP-1 receptor agonists in the proposed treatment paradigm highlights the expanding role of these peptide-based drugs beyond diabetes and obesity into neuroprotection.","specificNumbers":"Gut-kidney-brain axis · Uremic toxins impair BBB + neurogenesis + neuroinflammation · Mediterranean & DASH diets beneficial · GLP-1RA + SGLT2i proposed as pharmacological adjuncts","methodology":"Narrative review examining the mechanisms linking chronic kidney disease to cognitive impairment through the gut-kidney-brain axis, and evaluating nutritional, lifestyle, and pharmacological strategies for preserving brain health in CKD patients.","limitations":"This is a narrative review without new primary data. The evidence for GLP-1 receptor agonists and SGLT2 inhibitors specifically preserving cognitive function in CKD patients is still emerging — most evidence comes from their effects in diabetes populations rather than CKD-specific studies. The optimal combination of dietary, physical activity, and pharmacological interventions has not been established through randomized trials."},{"rthcId":"RPEP-15518","title":"Empowering exhausted T cells of Glioblastoma patients by Neurotransmitters and Neuropeptides: decreasing immune checkpoint inhibitors, and increasing CD3zeta, proliferation and Glioblastoma arrest.","authors":"Levite, Mia; Ilouz, Nili; Galun, Eithan; Shoshan, Yigal","year":2026,"journal":"Cancer immunology, immunotherapy : CII, 75(2), 54","doi":"10.1007/s00262-025-04226-6","pmid":"41591460","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15519","title":"The role of amygdala calcitonin gene-related peptide receptors on the development of persistent bladder pain in mice.","authors":"Lewter, Lakeisha A; Paul, Blesson K; Salazar, Arnold M; Chatterjee, Uma R; Pham, Hoai Phuong T; Khan, Myra Z; Schmitz, Anna E; Nofal, Abraham M; Hussein, Mursal M; Mysorekar, Indira U; Kolber, Benedict J","year":2026,"journal":"Pain","doi":"10.1097/j.pain.0000000000003939","pmid":"41711181","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15520","title":"Screening of the Non-Natural Antioxidant Peptide CVGVA and Its Application To Promote Burn Wound Healing.","authors":"Li, Ce; Cao, Yang; Wang, Yumei; Ren, Zekai; Liu, Xin; Li, Degang; Su, Bin; Cong, Hailin; Yu, Bing","year":2026,"journal":"ACS biomaterials science & engineering, 12(1), 284-298","doi":"10.1021/acsbiomaterials.5c01556","pmid":"41399294","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15521","title":"Activation of GLP-1R ameliorates microglial pyroptosis after spinal cord injury by restoring FANCC expression.","authors":"Li, Guangshen; Luo, Yang; Zhu, Tianyu; Chen, Chunmao; Qian, Zhanyang; Li, Haijun","year":2026,"journal":"Brain, behavior, and immunity, 134, 106295","doi":"10.1016/j.bbi.2026.106295","pmid":"41580096","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"High-dose liraglutide significantly improved functional and tissue outcomes in a mouse spinal cord injury model by suppressing microglial pyroptosis — an inflammatory form of cell death. These benefits were completely abolished in mice lacking the GLP-1 receptor (GLP-1R-/- mice), confirming the effect is GLP-1R-dependent.\n\nThe study mapped a novel signaling pathway: GLP-1R → PI3K/Akt → TFEB → FANCC upregulation → p38 suppression → NLRP3 inflammasome inhibition. Critically, when FANCC was knocked down, liraglutide's anti-inflammatory effects were blocked, establishing FANCC as an essential mediator of this neuroprotective cascade.","whyItMatters":"Spinal cord injuries currently have very limited treatment options. This research reveals that GLP-1 receptor agonists — drugs already approved and widely used for diabetes — could potentially be repurposed to reduce the secondary damage that worsens paralysis and disability after spinal cord injury.","specificNumbers":"","methodology":"Researchers used a mouse spinal cord injury model and compared outcomes in wild-type vs. GLP-1R knockout mice treated with high-dose liraglutide. In vitro experiments used RNA sequencing, pharmacological inhibitors, and genetic knockdown approaches to map the complete signaling pathway from GLP-1R activation to pyroptosis inhibition.","limitations":"This is entirely a preclinical study in mice, and spinal cord injury models in rodents have historically had poor translation to human outcomes. The study used high-dose liraglutide independent of metabolic effects, and it's unclear what doses would be needed in humans. Long-term outcomes and whether the functional improvements are sustained were not reported."},{"rthcId":"RPEP-15522","title":"Antimicrobial peptide SCY2 with its interacting proteins Scyreprocin mediate the innate immune defense of Scylla paramamosain against Pseudomonas putida infection.","authors":"Li, Hanxiao; Wang, Ying; Bai, Yuqi; Chen, Fangyi; Wang, Ke-Jian","year":2026,"journal":"International journal of biological macromolecules, 338(Pt 2), 149596","doi":"10.1016/j.ijbiomac.2025.149596","pmid":"41435952","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15523","title":"GLP-1 Receptor Agonists and Risk of Optic Nerve or Vision-Threatening Events in Patients With Type 2 Diabetes or Cardiometabolic Diseases: A Meta-analysis of Randomized Controlled Trials.","authors":"Li, Hoi-Ying; Chan, Tsz-Kwan; Co Shih, Kendrick; Cheung, Bernard M Y; Yiu, Kai-Hang; Tse, Hung-Fat; Chan, Yap-Hang","year":2026,"journal":"Diabetes care, 49(3), 526-535","doi":"10.2337/dc25-1929","pmid":"41587563","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15524","title":"Genome-Driven Discovery of Anti-MDR Bacterial Heptapeptides from a Cold-Seep-Derived Bacillus Strain.","authors":"Li, Hongcheng; Cheng, Yongmeng; Xing, Kaishuai; Li, Wenli; Xiao, Fei","year":2026,"journal":"Molecules (Basel, Switzerland), 31(3)","doi":"10.3390/molecules31030547","pmid":"41683524","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15525","title":"Efficacy of semaglutide in IgA nephropathy with obesity: a case report.","authors":"Li, Hongfen; Jia, Junya; Wei, Li; Shang, Wenya; Liu, Youxia","year":2026,"journal":"BMC nephrology, 27(1)","doi":"10.1186/s12882-026-04784-6","pmid":"41629851","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15526","title":"Injectable Schiff base-engineered hydrogel for spatiotemporal liraglutide delivery orchestrates diabetic periodontitis regression via multimodal microenvironment reprogramming.","authors":"Li, Jiamin; Li, Rongrong; Zhou, Yan; Zheng, Shengping; Xu, Jingjing; Zhu, Jingli; Pang, Yunqing; Wang, Jing","year":2026,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 392, 114688","doi":"10.1016/j.jconrel.2026.114688","pmid":"41651380","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15527","title":"Metabolic benefits of 1,3-diacylglycerol in type 2 diabetes mellitus and its association with gut microbiota-derived SCFAs-GPR41-GLP-1 signaling.","authors":"Li, Jiaomei; Wang, Hao; Yang, Jiekai; Wang, Yicheng; Jia, Guo; Gu, Jiaojiao","year":2026,"journal":"Food & function, 17(2), 734-749","doi":"10.1039/d5fo03164h","pmid":"41405391","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Both low-dose (50% DAG) and high-dose (100% DAG) 1,3-diacylglycerol significantly reduced fasting blood glucose, insulin, and triglycerides in T2DM rats to near-control levels over 8 weeks. 1,3-DAG restored colonic morphology, increased GPR41 receptor expression, and elevated GLP-1 and PYY secretion while reducing serum lipopolysaccharide (a marker of gut barrier leakage).\n\nGut microbiota analysis showed enrichment of Bacteroidota and depletion of Proteobacteria, with increased short-chain fatty acids (acetate, propionate, valerate). Bacteroidota taxa negatively correlated with blood sugar and lipid markers, while Proteobacteria positively correlated with LDL-C. The benefits appear mediated through a gut microbiota → SCFA → GPR41 → GLP-1 signaling axis.","whyItMatters":"GLP-1 and PYY are peptide hormones central to blood sugar and appetite regulation. While drugs like semaglutide provide these hormones externally, this study shows a dietary intervention that naturally boosts the body's own production of these peptides through the gut microbiome. This could offer an accessible, food-based complementary approach to diabetes management.","specificNumbers":"","methodology":"Male Wistar rats were fed a high-fat, high-sugar diet with weekly STZ injections (30 mg/kg) for 4 weeks to induce T2DM. After confirming stable hyperglycemia, rats were randomized to: healthy control, T2DM model, low-dose 1,3-DAG (50% DAG + 50% TAG), and high-dose 1,3-DAG (100% DAG) for 8 weeks. Outcomes included fasting glucose, insulin, lipids, colonic histology, GPR41 expression, GLP-1, PYY, serum LPS, 16S microbiota sequencing, and fecal SCFA levels by GC.","limitations":"This is an animal study using a chemical (STZ) diabetes model that may not fully replicate human type 2 diabetes. Specific group sizes were not stated in the abstract. The 8-week duration is relatively short. The causal pathway (microbiota → SCFA → GPR41 → GLP-1) is correlative in this study — direct causation would require microbiota transfer or GPR41 knockout experiments. Human studies are needed to confirm whether dietary 1,3-DAG produces similar effects."},{"rthcId":"RPEP-15528","title":"GYG1 as a Dual Biomarker of Glucagon-Like Peptide-1 Receptor Agonist Weight-Loss Response: Findings from an Integrative Multi-Omics Substudy of a Phase II Trial.","authors":"Li, Lijun; Hou, Mengyu; Gao, Qiannan; Dong, Ruihua","year":2026,"journal":"Endocrinology and metabolism (Seoul, Korea)","doi":"10.3803/EnM.2025.2641","pmid":"41634531","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GYG1 (glycogenin-1) emerged as a dual-function biomarker for GLP-1 receptor agonist therapy: baseline GYG1 levels predicted the trajectory of weight loss (BMI slope), while changes in GYG1 during treatment tracked ongoing treatment response (%BMI change).\n\nThe GLP-1RA GZR18 produced dose-dependent BMI reductions, with the 48 mg biweekly dose yielding the steepest declines. Gene set enrichment analysis revealed that starch/sucrose metabolism pathways modulated ongoing drug efficacy through integrated molecular networks.","whyItMatters":"GLP-1 receptor agonists like semaglutide and tirzepatide have transformed obesity treatment, but not everyone responds equally well. A reliable blood-based biomarker that predicts who will benefit most — and monitors response in real time — could enable truly personalized obesity therapy, helping doctors choose the right drug and dose for each patient.","specificNumbers":"","methodology":"Longitudinal multi-omics profiling (proteomics, metabolomics, and lipidomics) was performed on 221 plasma samples from 25 participants treated with GZR18 across nine time points over 30 weeks. High-resolution mass spectrometry was used for molecular quantification. Theil-Sen regression modeled baseline predictors, while linear regression identified longitudinal biomarkers. Significant candidates were validated through gene set enrichment analysis (KEGG pathways) and STRING protein network integration.","limitations":"The study had a very small sample size (n=25), which limits the statistical power and generalizability of the findings. Results come from a substudy of a single Phase II trial of one specific GLP-1RA (GZR18) and may not apply to other drugs in the class. External validation in larger, independent cohorts is needed before GYG1 can be used clinically."},{"rthcId":"RPEP-15529","title":"Low-dose lipopolysaccharide pretreatment enhanced the proliferation and antibacterial activity of human adipose-derived mesenchymal stem cells.","authors":"Li, Linling; Diao, Jielin; Wang, Feng; Wang, Xia; Liu, Yicai; Fu, Xiaoming","year":2026,"journal":"Regenerative therapy, 31, 101057","doi":"10.1016/j.reth.2025.101057","pmid":"41541822","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"LPS preconditioning at 10-500 ng/mL enhanced hADSC proliferation (maximal at 500 ng/mL) without increasing apoptosis. It markedly upregulated antimicrobial peptides LL-37 and HBD-2, improving S. aureus and E. coli inhibition. In vivo, 500 ng/mL LPS-conditioned medium accelerated infected wound healing, increased collagen deposition, and reduced iNOS expression.","whyItMatters":"Chronically infected wounds affect millions of patients, especially those with diabetes and poor circulation. Enhancing stem cells' antimicrobial peptide production through simple preconditioning could create more effective cell-based wound treatments.","specificNumbers":"10-500 ng/mL LPS range; 500 ng/mL optimal; LL-37 and HBD-2 upregulated; S. aureus and E. coli inhibited; iNOS downregulated in vivo","methodology":"Human ADSCs were pretreated with LPS at various concentrations. Proliferation and apoptosis were assessed. Conditioned medium was tested for antimicrobial peptide expression (LL-37, HBD-2) and bacterial growth inhibition against S. aureus and E. coli. In vivo wound healing was evaluated in an infected wound model measuring healing rate, collagen deposition, and inflammation markers.","limitations":"Preclinical study — human clinical validation needed. The LPS preconditioning approach introduces a bacterial product that could raise safety concerns. Only two bacterial species tested. The in vivo model details and animal numbers are not specified. Long-term safety of LPS-preconditioned stem cell therapy is unknown."},{"rthcId":"RPEP-15530","title":"Evaluating Semaglutide's Protection in H/R - Injured AC16 Cardiomyocytes: Oxidative Stress, Inflammation, Apoptosis, and Autophagy Insights.","authors":"Li, Liqin; Jin, Lili; Wang, Jun","year":2026,"journal":"International journal of general medicine, 19, 564902","doi":"10.2147/IJGM.S564902","pmid":"41737537","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15531","title":"The multifaceted role of GLP-1 in metabolic disorders, chronic inflammation, and aging: Mechanisms and therapeutic potential.","authors":"Li, Mo; Xu, Shenghao; Cai, Hanqing; Xiao, Jianlin; Qin, Yanguo","year":2026,"journal":"Metabolism: clinical and experimental, 178, 156547","doi":"10.1016/j.metabol.2026.156547","pmid":"41672302","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15532","title":"Ultrasound Controlled-Release Hydrogel Promotes Diabetic Wound Healing via Neuroimmune Modulation and Synergistic ROS Scavenging.","authors":"Li, Mofan; Wang, Mengxin; Wang, Haonan; Sun, Yang; Zhang, Yongyue; Xu, Shuyu; Zhang, Tianjiao; Shama, Shiti; Liang, Xiaolong; Wang, Shumin","year":2026,"journal":"Advanced science (Weinheim, Baden-Wurttemberg, Germany), e16882","doi":"10.1002/advs.202516882","pmid":"41560627","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The MCF@CA hydrogel system, when activated by ultrasound, delivered CGRP-conjugated nanoparticles that simultaneously modulated the immune microenvironment and scavenged reactive oxygen species. In diabetic wound models, the treatment enhanced collagen deposition, promoted macrophage polarization from the pro-inflammatory M1 state to the anti-inflammatory M2 phenotype, and improved local blood supply — all of which contributed to significantly faster wound closure compared to controls.","whyItMatters":"Diabetic wounds affect millions of people worldwide and are a leading cause of non-traumatic amputations. Current treatments often fail because they don't address the underlying immune dysfunction. This approach is notable because it tackles two problems at once — calming runaway inflammation through a neuropeptide and cleaning up tissue-damaging ROS — while giving clinicians precise control over when and how much drug is released.","specificNumbers":"","methodology":"Researchers synthesized an amphiphilic prodrug by chemically linking CGRP to manganese porphyrin (MnP), then co-assembled it with a folic-acid-tagged lipid to create targeted nanoparticles (MCF). These were loaded into an ultrasound-responsive hydrogel. The system was tested in diabetic animal wound models, where ultrasound was applied locally to trigger on-demand drug release. Wound healing outcomes including collagen deposition, immune cell behavior, and blood vessel formation were evaluated.","limitations":"This study was conducted in animal models only, so it's unknown whether the results will translate to human diabetic wounds. The abstract does not report specific quantitative wound-closure rates or statistical comparisons. The complexity of the multi-component delivery system (prodrug synthesis, nanoparticle assembly, hydrogel loading, ultrasound equipment) could present challenges for clinical translation and manufacturing scale-up."},{"rthcId":"RPEP-15533","title":"Neuropeptide FF enhances antimicrobial defense by promoting intestinal barrier function in grass carp (Ctenopharyngodon idella).","authors":"Li, Pingyuan; Liu, Jiaxin; Hu, Jiayi; Yang, Ye; Liu, Yujun; Zeng, Chuyi; Tang, Yiyang; Cai, Jianguang; Zhou, Zejun","year":2026,"journal":"Fish & shellfish immunology, 169, 111052","doi":"10.1016/j.fsi.2025.111052","pmid":"41338478","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15534","title":"GLP-1 receptor agonists and aneurysm rupture risk in type 2 diabetes: a multicenter retrospective study.","authors":"Li, Sean Y; Sonti, Anisha; Kaelber, David C; Ben-Israel, David; Bowles, Alfred; Reddy, Deven; Kelly, Michael L","year":2026,"journal":"Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia, 147, 111905","doi":"10.1016/j.jocn.2026.111905","pmid":"41671787","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"From 24,776 T2DM patients with unruptured intracranial aneurysms identified in the TriNetX Research Network, propensity score matching produced 2,651 patients in each group (GLP-1RA users vs. non-users).\n\nGLP-1RA use was associated with significantly reduced risk of nontraumatic subarachnoid hemorrhage (SAH):\n- 3-year follow-up: HR 0.62 (95% CI: 0.44–0.88) — 38% risk reduction\n- 5-year follow-up: HR 0.65 (95% CI: 0.47–0.92) — 35% risk reduction\n\nFollow-up laboratory values showed no significant differences between groups, suggesting the protective effect is not simply mediated by metabolic improvements.","whyItMatters":"Brain aneurysm rupture is one of the most feared neurological emergencies, with about 50% mortality. Currently, the only way to prevent rupture is surgical clipping or endovascular coiling — invasive procedures with their own risks. If GLP-1 drugs can stabilize aneurysms and reduce rupture risk through a simple medication, it could transform management for the millions of people living with unruptured brain aneurysms.","specificNumbers":"","methodology":"This multicenter retrospective cohort study used the TriNetX Research Network to identify adults with type 2 diabetes and unruptured intracranial aneurysms between 2008 and 2025. Patients were classified as GLP-1RA users or non-users. One-to-one propensity score matching balanced demographics, comorbidities, laboratory values, and medication use. The primary outcome was nontraumatic subarachnoid hemorrhage at 3 and 5 years.","limitations":"This is a retrospective observational study that cannot prove causation. Despite propensity score matching, unmeasured confounders may exist. The study used administrative diagnosis codes for SAH, which may have coding inaccuracies. It cannot determine whether GLP-1 RAs prevent aneurysm formation, growth, or rupture specifically. Aneurysm size, location, and morphology were not controlled for. The study population was limited to T2DM patients, so results may not generalize to non-diabetic individuals."},{"rthcId":"RPEP-15535","title":"Parthenolide promotes glucagon-like peptide-1 secreting in human Caco-2 cells via regulation of bitter taste receptor-induced of calcium signaling.","authors":"Li, Shanshan; Chen, Ye; Song, Zhaosu; Ou, Penghui; Duan, Yujing; Liu, Qinglei; Wang, Wei","year":2026,"journal":"Molecular and cellular biochemistry, 481(2), 775-789","doi":"10.1007/s11010-025-05425-6","pmid":"41182647","tags":["glp-1-secretion","natural-compounds"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Parthenolide (PTL), a natural compound found in feverfew, was identified as a high-affinity agonist of the bitter taste receptor TAS2R4 that stimulates GLP-1 secretion from human intestinal cells in a dose-dependent manner. Direct binding to TAS2R4 was confirmed by cellular thermal shift assays, and molecular docking revealed strong interactions including hydrogen bonding with specific receptor residues.\n\nThe mechanism involves PTL activating TAS2R4, which upregulates phospholipase C β2 (PLCβ2) to produce IP3, triggering calcium release inside the cell. This calcium increase drives GLP-1 vesicle fusion and secretion. Calcium also activates the TRPM5 channel, further amplifying the signal. This establishes parthenolide as a natural compound that can boost the body's own GLP-1 production through a bitter taste receptor pathway.","whyItMatters":"GLP-1 drugs like semaglutide are revolutionizing diabetes and obesity treatment, but they require injections and are expensive. An alternative approach is to stimulate the body's own GLP-1 production using natural compounds. Bitter taste receptors in the gut — the same type that detect bitterness on the tongue — can trigger GLP-1 release when activated. Finding natural agonists for these receptors could lead to functional foods or supplements that boost endogenous GLP-1, potentially offering a dietary complement to pharmaceutical approaches for blood sugar management.","specificNumbers":"Parthenolide: high-affinity TAS2R4 agonist · dose-dependent GLP-1 secretion · hydrogen bonding with ASN-65 · hydrophobic contacts with PHE-62 and PHE-88 · calcium-dependent vesicle fusion · PLCβ2/IP3/TRPM5 signaling pathway","methodology":"Researchers screened the BitterDB and BitterX databases to identify natural bitter compounds with GLP-1-inducing potential. Parthenolide was selected as a TAS2R4 agonist candidate. Direct binding was confirmed by cellular thermal shift assay (CETSA). Molecular docking revealed specific binding interactions. GLP-1 secretion was measured in human Caco-2 enteroendocrine cells after parthenolide treatment. Intracellular signaling was characterized through TAS2R4 expression analysis, PLCβ2 pathway activation, calcium imaging, and TRPM5 channel involvement.","limitations":"This is entirely an in vitro study using Caco-2 cells (a human colon cancer cell line used to model intestinal cells), not primary human gut cells or in vivo testing. Caco-2 cells may not perfectly replicate the GLP-1 secretion dynamics of native L-cells in the human intestine. No animal or human data exists for parthenolide's GLP-1-stimulating effects. Parthenolide's bioavailability, safety profile at GLP-1-stimulating doses, and potential interactions with other medications are not addressed."},{"rthcId":"RPEP-15536","title":"Vm-MSI: a Vancomycin-Antimicrobial Peptide Conjugate Combating Resistant Bacteria and Broadening the Antimicrobial Spectrum.","authors":"Li, Shuangyu; Wang, Kang; Shi, Wenzhuang; Wang, Xu; Li, Duxin; Liu, Yanli; Zhang, Peng; Wang, Yipeng","year":2026,"journal":"Advanced science (Weinheim, Baden-Wurttemberg, Germany), 13(11), e03023","doi":"10.1002/advs.202503023","pmid":"41361722","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15537","title":"A Case Report of a Multisystemic Immune-Related Adverse Event Caused by Sintilimab in Combination With Thymosin Alpha-1.","authors":"Li, Ting; Wu, Bao-Liang; Yu, Cai-Long; Jin, Liang-Yan","year":2026,"journal":"Clinical case reports, 14(2), e72025","doi":"10.1002/ccr3.72025","pmid":"41669704","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15538","title":"Potent dual-function of marine peptide N6NH2 and its D-enantiomer to combat MDR A. veronii infection in tilapia (GIFT, Oreochromis niloticus).","authors":"Li, Ting; Yang, Na; Teng, Da; Mao, Ruoyu; Hao, Ya; Han, Huihui; Wu, Yankang; Wang, Xiumin; Wang, Jianhua","year":2026,"journal":"Fish & shellfish immunology, 170, 111132","doi":"10.1016/j.fsi.2026.111132","pmid":"41544990","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"At 10 mg/kg, the D-enantiomer peptide DN6NH2 achieved 81.82% survival in tilapia with A. veronii peritoneal infection, compared to 51.52% for the parent peptide N6NH2 and just 30.30% for the conventional antibiotic florfenicol at the same dose.\n\nHistopathology showed DN6NH2-treated fish had significantly reduced inflammation, bleeding, and necrosis in liver, intestine, spleen, and gills. DN6NH2 also alleviated excessive immune responses in the spleen and head kidney and significantly reduced NF-κB p65 levels in the spleen, demonstrating both antimicrobial and immunomodulatory dual-function activity.","whyItMatters":"Antibiotic overuse in aquaculture is a major driver of antimicrobial resistance globally, threatening both animal and human health. Finding effective alternatives to conventional antibiotics for fish farming is urgent. This study demonstrates that antimicrobial peptides — particularly D-enantiomer forms that resist enzymatic degradation — can dramatically outperform standard antibiotics against resistant infections, while also providing anti-inflammatory benefits that reduce tissue damage.","specificNumbers":"","methodology":"Tilapia (GIFT strain, Oreochromis niloticus) were infected with multidrug-resistant A. veronii through peritoneal injection to create an acute infection model. Fish were treated with N6NH2, its D-enantiomer DN6NH2, or the veterinary antibiotic florfenicol (all at 10 mg/kg). Survival was tracked, and organs (liver, intestine, spleen, gills) were examined by H&E staining for histopathology. Immune gene expression was measured by RT-qPCR in spleen and head kidney. NF-κB p65 protein levels were assessed in the spleen.","limitations":"This is an animal (fish) study that cannot be directly applied to human medicine. The experiment used a single bacterial pathogen (A. veronii) and a single fish species. Cost-effectiveness of peptide production at aquaculture scale was not addressed. The study did not test for development of peptide resistance over time. Specific mechanisms of the D-enantiomer's enhanced activity (beyond protease resistance) were not fully elucidated. Long-term effects on fish health and the aquatic environment were not assessed."},{"rthcId":"RPEP-15539","title":"Exercise alleviates allodynia and hyperalgesia concomitant with improvements in aberrant primary afferents and spinal circuit inhibition in the dorsal horn of rats with incomplete spinal cord injury.","authors":"Li, Xiangzhe; Wu, Jiahuan; Fang, Lu; Wang, Jiale; Wang, Sheng; Wu, Qinfeng; Wang, Tong","year":2026,"journal":"PeerJ, 14, e20699","doi":"10.7717/peerj.20699","pmid":"41664649","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15540","title":"Prevalence and predictors of residual gastric content in patients with type 2 diabetes on GLP-1 receptor agonists: A prospective observational study.","authors":"Li, Xiao-Yu; Jin, Yun; Feng, Xiu-Ye; Wang, Rui-Chun; Zeng, Fan-Fu; Qin, Jin-Ling; Li, Jian-Hui; Xia, Jin-Ying; Mo, Ye-Ping; Zhai, Xiao-Jie; Chen, Jun-Ping; Lu, Bo","year":2026,"journal":"Diabetes, obesity & metabolism","doi":"10.1111/dom.70537","pmid":"41635113","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15541","title":"Liraglutide alleviates sepsis-associated encephalopathy via attenuating neuronal damage, glial cell activation and mitochondrial dysfunction in a mouse model of sepsis.","authors":"Li, Xiaoming; Wang, Jun; Zhang, Rongji; He, Haoran; Wang, Linjue; Wang, Yuliang; Yi, Hongyu","year":2026,"journal":"European journal of medical research, 31(1)","doi":"10.1186/s40001-026-03974-0","pmid":"41622219","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Intracerebroventricular liraglutide administered 1 hour before cecal ligation and puncture (CLP) alleviated neurological impairment scores and reduced glial cell activation, neuronal loss, and neurodegeneration in the hippocampus of septic mice. In vitro, liraglutide suppressed neuron-microglia interaction under LPS stimulation. Liraglutide also inhibited mitochondrial damage and oxidative stress in hippocampal neurons. The mechanism involved restoring diminished p-AKT levels while reversing STAT3 phosphorylation in hippocampal neurons. Neurological severity scores, weight loss, food intake, and survival were monitored for up to 5 days post-CLP.","whyItMatters":"Sepsis-associated encephalopathy affects up to 70% of ICU sepsis patients and is linked to increased mortality and long-term cognitive disability. No targeted treatment exists — management is limited to treating the underlying infection. Liraglutide is already approved and widely used, making it an attractive candidate for repurposing. Demonstrating neuroprotective effects in sepsis adds to the expanding evidence of GLP-1 drugs' benefits beyond metabolism.","specificNumbers":"","methodology":"Male C57BL/6J mice were divided into three groups: CLP (sepsis model), CLP + liraglutide (intracerebroventricular), and sham operation. Liraglutide was administered 1 hour before CLP surgery. Brain tissue was analyzed by immunohistochemistry, transmission electron microscopy, and Western blot at day 1 post-CLP. Modified neurological severity scores were assessed at days 0, 1, 3, and 5. In vitro experiments used BV2 microglial cells and HT22 hippocampal neurons to assess neuron-microglia interactions under LPS stimulation.","limitations":"Liraglutide was delivered directly into the brain (intracerebroventricularly), which is not a practical clinical route — it's unclear whether systemic injection would achieve the same brain concentrations. The drug was given pre-treatment (1 hour before CLP), whereas clinical use would need to work after sepsis onset. Small animal numbers typical of mouse studies limit statistical power. Only male mice were studied, and sex differences in sepsis outcomes are well-documented."},{"rthcId":"RPEP-15542","title":"Sleeve Gastrectomy with Fundoplication Enhances Metabolic Health in Obese Rats via Ghrelin Pathway Modulation and Multi-Organ Regulation.","authors":"Li, Xin; Aili, Aikebaier; Tusuntuoheti, Yusujiang; Aierken, Yusunjiang; Abudureyimu, Kelimu; Liu, Weihui","year":2026,"journal":"Diabetes & metabolism journal","doi":"10.4093/dmj.2025.0392","pmid":"41548896","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15543","title":"Mechanism of Self-Assembly of the Gonadropin Releasing Hormone Antagonist Teverelix into Amyloid Fibrils.","authors":"Li, Xinyang; Serpell, Louise C; Bukrinski, Jens T; Boutignon, Francois; MacLean, Carol M; Jackson, Sophie E","year":2026,"journal":"Molecular pharmaceutics, 23(1), 164-176","doi":"10.1021/acs.molpharmaceut.5c00578","pmid":"41411501","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15544","title":"Exenatide through PPARδ improved hepatic insulin resistance in patients of type 2 diabetes mellitus via suppressing pyroptosis.","authors":"Li, Xizhi; Zhou, Tingting; Wu, Yixi; Sun, Jiayi; Wang, Ziyu; Huang, Yuhan; Xu, Ke; Ling, Hongwei; Li, Na; Yang, Tingting; Wang, Tao","year":2026,"journal":"International immunopharmacology, 175, 116416","doi":"10.1016/j.intimp.2026.116416","pmid":"41723896","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Exenatide (the first GLP-1 receptor agonist peptide drug) was found to improve hepatic insulin resistance by directly binding to and upregulating PPARδ, which in turn suppresses pyroptosis — an inflammatory form of cell death. Knocking down PPARδ abolished exenatide's protective effects, while activating PPARδ enhanced them, confirming PPARδ as a key mediator.\n\nClinically, T2DM patients carrying the AA genotype at PPARD rs3777744 and having higher baseline insulin resistance (HOMA-IR) showed a superior response to exenatide, suggesting this genetic variant could serve as a biomarker for personalized GLP-1 therapy.","whyItMatters":"This study reveals a previously unknown mechanism by which GLP-1 peptide drugs improve liver insulin resistance — through PPARδ-mediated suppression of inflammatory cell death. The pharmacogenomic finding that a specific PPARD gene variant predicts better exenatide response points toward personalized medicine, where genetic testing could help identify which diabetes patients will benefit most from GLP-1 peptide therapy.","specificNumbers":"PPARD rs3777744 AA genotype = better response · PPARδ knockdown abolished protection · Higher baseline HOMA-IR = greater benefit · Both in vitro and in vivo validation","methodology":"Combined approach: in vitro studies with hepatic cells measuring pyroptosis markers and insulin signaling after exenatide treatment with and without PPARδ manipulation (knockdown and pharmacological activation). In vivo animal studies confirmed PPARδ-dependent effects. Clinical pharmacogenomic analysis of T2DM patients examined whether PPARD rs3777744 genotype and baseline HOMA-IR predicted exenatide treatment response.","limitations":"The clinical pharmacogenomic analysis appears observational rather than from a randomized trial designed for this purpose. The specific number of patients analyzed and the strength of the genotype-response association need examination in larger, prospective studies. The PPARδ binding mechanism is novel and requires independent confirmation. Pyroptosis is a complex process, and the full pathway from exenatide to PPARδ to NLRP3 inflammasome suppression may involve additional mediators."},{"rthcId":"RPEP-15545","title":"People With Lowest Physical Functioning Scores Showed Greatest Improvement After Tirzepatide Treatment.","authors":"Li, Xuan; Cao, Dachuang; Sapin, Helene; Wang, Fangyu; Hunter Gibble, Theresa; Raibulet, Nedina Kalezic; Denning, Max; Kaplan, Lee M","year":2026,"journal":"Obesity (Silver Spring, Md.), 34(1), 114-126","doi":"10.1002/oby.70067","pmid":"41187013","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15546","title":"Oncostatin M promotes chronic pain through direct regulation on nociceptors in rats.","authors":"Li, Yan; Uhelski, Megan L; North, Robert Y; Elahi, Hajira; Corrales, German; Abercrombie, Taylor J; Sheffield, Katherine N; Marri, Tejaswi; Price, Theodore J; Dougherty, Patrick M","year":2026,"journal":"Pain","doi":"10.1097/j.pain.0000000000003922","pmid":"41610043","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15547","title":"Effects of Tanshinone IIA on Calcium Overload and Pyroptosis in Radiation-induced Heart Disease Evaluated in Vivo and in Vitro.","authors":"Li, Yan-Ling; Wang, Gang; Shu, Yan-Biao; Wang, Bo-Wen; Huang, Yuan; Yan, Wen-Ting; Yan, Heng-Yu; Xie, Ping","year":2026,"journal":"Radiation research, 205(1), 87-99","doi":"10.1667/RADE-25-00031.1","pmid":"41182914","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15548","title":"Clinical Efficacy of Abdominal Massage Combined With Moxibustion for Treatment of Chronic Constipation in Elderly Patients.","authors":"Li, Yanan; Li, Xiaowei; Zang, Jingpeng; Hao, Lili; Gao, Yawei; Liao, Ying","year":2026,"journal":"Neurogastroenterology and motility, 38(1), e70207","doi":"10.1111/nmo.70207","pmid":"41240062","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15549","title":"Biomimetic antimicrobial peptides against gram-positive bacteria.","authors":"Li, Yu-Ting; Wei, Tian-Ci; Yuan, Jun-Xiao; Feng, Jia-Qi; Yang, Pei-Pei; Tang, Shu-Sheng; Wang, Lei; Wang, Hao","year":2026,"journal":"Biomaterials, 329, 123916","doi":"10.1016/j.biomaterials.2025.123916","pmid":"41411843","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15550","title":"Algorithm-Based Common Microcirculatory Framework for Monitoring and Visualizing the Integrated Pancreatic Microcirculation in Type 2 Diabetes Mellitus Mice.","authors":"Li, Yuan; Wang, Yingyu; Wang, Bing; Liu, Weiqi; Xu, Mengting; Zhang, Xiaoyan; Liu, Xueting; Ling, Hao; Zhang, Xu; Liu, Mingming; Xiu, Ruijuan","year":2026,"journal":"Journal of diabetes, 18(2), e70188","doi":"10.1111/1753-0407.70188","pmid":"41635279","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"T2DM mice showed decreased blood perfusion, reduced red blood cell tissue fraction, diminished oxygen saturation, and lower hemoglobin concentration in pancreatic microcirculation compared to controls. Liraglutide treatment significantly ameliorated these impairments, partially restoring the balance between blood perfusion and oxygen saturation and normalizing the disrupted coherence between oxygenated hemoglobin and speed-resolved blood perfusion.\n\nThe study also validated a new algorithm-based framework for simultaneously monitoring microhemodynamics and oxygen profiles in the pancreas, providing a tool for future research on pancreatic microcirculation.","whyItMatters":"Pancreatic islet dysfunction in type 2 diabetes may be partly caused by impaired blood supply — if insulin-producing beta cells don't receive enough oxygen and nutrients, they can't function properly. This study shows liraglutide improves pancreatic microcirculation, suggesting a protective mechanism beyond glucose control that could help preserve beta cell function long-term.","specificNumbers":"","methodology":"Researchers developed a common microcirculatory framework using laser Doppler and diffuse reflectance spectroscopy to simultaneously measure pancreatic blood flow and oxygen parameters. The analytical pipeline used boxplot outlier adjustment and comparative normalization strategies (Z-score, min-max, L2, median scaling). The framework was validated in a T2DM mouse model comparing insulin-treated, liraglutide-treated, and control groups. Heat maps and chord plots visualized the integrated dynamics.","limitations":"The study was conducted in mice with chemically or diet-induced diabetes, which may not fully replicate human type 2 diabetes pancreatic pathology. The novel monitoring framework, while validated, is new and requires further independent validation. Specific quantitative improvements from liraglutide treatment were not detailed in the abstract. Whether improved microcirculation translates to preserved beta cell mass or function over time was not assessed."},{"rthcId":"RPEP-15551","title":"Rapid improvement of renal microcirculatory homeostasis by liraglutide following diabetes induction.","authors":"Li, Yuan; Liu, Weiqi; Wang, Yingyu; Wang, Bing; Xu, Xiang; Li, Bingwei; Liu, Mingming; Zhang, Xu; Xiu, Ruijuan","year":2026,"journal":"Diabetes, obesity & metabolism","doi":"10.1111/dom.70594","pmid":"41749403","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15552","title":"CGRP alleviates epilepsy via JAK1-STAT1-P2RX7 signaling: a novel neuroprotective axis targeting neuronal damage.","authors":"Li, Yuxiang; Sun, Jixiang; Lyu, Yanmin; Huang, Mengying; Du, Chunxiao; Liang, Meng; Chen, Junrui; Lu, Jiawen; Li, Ge; Wang, Zhiding; Han, Gencheng","year":2026,"journal":"International immunopharmacology, 170, 116080","doi":"10.1016/j.intimp.2025.116080","pmid":"41429063","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15553","title":"Cyclization and thermal modulation of a β-hairpin peptide for efficient cellular delivery.","authors":"Li, Zenghui; Yan, Qipeng; Han, Hong; Yuan, Dan; Schneider, Joel P; Shi, Junfeng","year":2026,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 390, 114551","doi":"10.1016/j.jconrel.2025.114551","pmid":"41412216","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15554","title":"Post-sleeve gastrectomy weight loss: Role of botulinum toxin and semaglutide injections.","authors":"Li, Zhengqi; Zhang, Shaohan; Nie, Yuntao; Wang, Pengpeng; Liu, Baoyin; Zhou, Biao; Zhang, Nianrong; Wang, Siqi; Chou, Sai; Zhang, Lei; Wang, Zhe; Meng, Hua","year":2026,"journal":"Endoscopy international open, 14, a27939945","doi":"10.1055/a-2793-9945","pmid":"41777326","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15555","title":"Targeted Neutrophil Extracellular Traps Mimics Combat Staphylococcus aureus Infections.","authors":"Li, Zhuo-Yue; Hu, Shao-Yu; Xu, Guo-Yang; Huang, Jing-Xian; Yang, Xi-You; Wei, Tian-Ci; Feng, Jia-Qi; Yuan, Jun-Xiao; Li, Chao-Ran; Li, Yu-Ting; Weng, Jie; Cui, Xu; Wang, Hao; Nie, Qiong; Wang, Lei; Li, Li-Tao","year":2026,"journal":"ACS infectious diseases","doi":"10.1021/acsinfecdis.5c00831","pmid":"41644356","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15556","title":"SGLT-2 Inhibitors and GLP-1 Receptor Agonists as Combination Therapy in Type 2 Diabetes.","authors":"Liakos, Aris; Karagiannis, Thomas; Avgerinos, Ioannis; Bekiari, Eleni","year":2026,"journal":"Current diabetes reports, 26(1), 1","doi":"10.1007/s11892-025-01616-z","pmid":"41528550","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15557","title":"Effect of the antimicrobial peptide BmKn2-7 in inhibiting Vibrio parahaemolyticus and its role in improving microbiota, immunity and Vibrio resistance in Litopenaeus vannamei.","authors":"Liang, Qihang; Wang, Qi; Chi, Pinqi; Fan, Depeng; Tan, Beiping; Xie, Shiwei; Deng, Junming; Liu, Hongyu; Zeng, Ling","year":2026,"journal":"BMC veterinary research, 22(1)","doi":"10.1186/s12917-025-05264-z","pmid":"41540432","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15558","title":"US Molecular Imaging of Glypican-3 Expression in Hepatocellular Carcinoma Using Targeted Biosynthetic Gas Vesicles.","authors":"Liang, Xiaoxin; Li, Lingling; Wang, Yuanyuan; Lu, Shilin; Han, Xu; Yan, Fei; Zhou, Jianhua","year":2026,"journal":"Radiology. Imaging cancer, 8(2), e250480","doi":"10.1148/rycan.250480","pmid":"41790017","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15559","title":"Decidualization-empowered ECM hydrogel integrating sustained Tβ4 release drives endometrial regeneration in intrauterine adhesions.","authors":"Liang, Yuxiang; Yu, Zhaowei; Du, Shaobo; Guo, Yuqian; Li, Jing; Yan, Yujia; Jin, Shanshan; Liang, Wenjing; Li, Mengyuan; Jin, Ning; Yang, Jiao; Peng, Zhiwei; Chen, Zhaoyang; Yang, Hailan; Liu, Zhizhen; Shuai, Qizhi; Li, Liping; Xie, Jun","year":2026,"journal":"Nature communications, 17(1)","doi":"10.1038/s41467-026-68677-w","pmid":"41565687","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15560","title":"Avidity-optimized TCR-T cells target KRAS neoantigens for potent cancer clearance and tumor microenvironment remodeling.","authors":"Liang, Zhaoduan; Guan, Fengqiong; Wu, Bingling; Chen, Wenfang; Tian, Ye; Cai, Wenxuan; Li, Yi","year":2026,"journal":"Frontiers in immunology, 17, 1736294","doi":"10.3389/fimmu.2026.1736294","pmid":"41668743","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The engineered TCR3-T cells demonstrated significantly enhanced avidity for the KRAS G12V8-16 neopeptide compared to the original TCR0-T cells, translating to effective tumor cell killing both in vitro and in vivo.\n\nCritically, TCR3-T cells overcame multiple tumor immune-evasion mechanisms: they killed tumor cells highly expressing PD-L1, proliferated despite exposure to indoleamine 2,3-dioxygenase (IDO), resisted transforming growth factor β (TGF-β) suppression, and recruited other immune cells to the tumor site via chemokines. TCR3-T cells retained specificity for the KRAS neopeptide with no reactivity against normal cells.","whyItMatters":"KRAS mutations drive roughly 25% of all human cancers, yet no approved immunotherapy directly targets KRAS neoantigens. This study demonstrates that engineering T-cell receptors for higher avidity can overcome the weak immune responses typically seen against KRAS, while also addressing tumor immune-escape mechanisms that have stymied other approaches.","specificNumbers":"","methodology":"Researchers isolated a natural human TCR (TCR0) from T cells that recognized HLA-A*11:01-presented KRAS G12V8-16 peptides. Finding TCR0 insufficient for tumor killing, they generated an avidity-optimized mutant (TCR3). TCR3-transduced T cells were tested against tumor cell lines in vitro for cytotoxicity, specificity, and resistance to immunosuppressive factors. In vivo efficacy was evaluated in tumor-bearing animal models, assessing tumor clearance and immune cell infiltration.","limitations":"No human clinical trial data are presented — results are from in vitro experiments and animal models. The therapy is restricted to HLA-A*11:01-positive patients (roughly 15–20% of the global population), limiting generalizability. Long-term safety, persistence of TCR3-T cells, and potential off-target toxicity in humans remain to be determined."},{"rthcId":"RPEP-15561","title":"Bioconvergence of sound-guided and supramolecular assembly strategies to create peptide-protein composite hydrogels with predictable shape-to-function features.","authors":"Ligorio, Cosimo; Cianciosi, Alessandro; Tognato, Riccardo; Natta, Micaela; Parolini, Romedi; Ardicli, Sena; Babayev, Huseyn; Sapjanskaite, Ieva; Kilgour, Samantha L; Homer, Richard; Pramanik, Bapan; Zhou, Zhiyu; Malandrino, Andrea; Priglinger, Eleni; Akdis, Cezmi; Stoddart, Martin J; Mata, Alvaro; Serra, Tiziano","year":2026,"journal":"Materials today. Bio, 36, 102643","doi":"10.1016/j.mtbio.2025.102643","pmid":"41560831","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15562","title":"Lunatin-1: A peptide derived from the venom of the Hadruroides lunatus scorpion modulates signaling pathways in HL60 tumor cells to induce cytotoxic effects.","authors":"Lima-Batista, Edleusa M; Gómez-Mendoza, Diana Paola; Moysés, Maurício Nogueira; de Sousa Gomes, Kamila; Carvalho, Brener Cunha; de Lima, Maria Elena; Souza-Fagundes, Elaine M; da Silva, Aristóbolo Mendes; Kjeldsen, Frank; Verano-Braga, Thiago; Pimenta, Adriano M C","year":2026,"journal":"Journal of proteomics, 324, 105571","doi":"10.1016/j.jprot.2025.105571","pmid":"41276073","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15563","title":"PepGraphormer: an ESM-GAT hybrid deep learning framework for antimicrobial peptide prediction.","authors":"Lin, Changhang; Xiong, Shuwen; Li, Jinjin; Cui, Feifei; Zhang, Zilong; Shi, Hua; Wei, Leyi","year":2026,"journal":"Journal of cheminformatics, 18(1), 15","doi":"10.1186/s13321-025-01144-8","pmid":"41491543","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15564","title":"Novel dual-functional peptides designed via NanoBiT spike pseudovirus system for real-time monitoring and inhibition of SARS-CoV-2 infection.","authors":"Lin, Cheng-Han; Chiang, Hua-Hsin; Yang, Xin-Rui; Lin, Tzu-Ching; Tsai, Chin-Hung; Lin, Chih-Sheng","year":2026,"journal":"European journal of medicinal chemistry, 305, 118568","doi":"10.1016/j.ejmech.2026.118568","pmid":"41518958","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15565","title":"Longitudinal and cross-sectional associations of myocardial stress markers with kidney function and chronic kidney disease in the BiomarCaRE project.","authors":"Lin, Jie-Sheng; Zeller, Tanja; Koenig, Wolfgang; Jousilahti, Pekka; Kee, Frank; Iacoviello, Licia; Tunstall-Pedoe, Hugh; Söderberg, Stefan; Cesana, Giancarlo; Palmieri, Luigi; Salomaa, Veikko; de Man Lapidoth, Julia; De Ponti, Roberto; Donfrancesco, Chiara; Lorenz, Thiess; Kuulasmaa, Kari; Blankenberg, Stefan; Peters, Annette; Thorand, Barbara","year":2026,"journal":"Scientific reports, 16(1)","doi":"10.1038/s41598-026-37377-2","pmid":"41724744","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In cross-sectional analysis of up to 61,830 participants, all three cardiac peptide markers — MR-proADM, MR-proANP, and NT-proBNP — were consistently associated with lower kidney function (eGFR) and higher CKD prevalence. Per 1 standard deviation increase in log-transformed NT-proBNP (corresponding to a 2.71-fold concentration increase), eGFR was 2.35 ml/min/1.73m² lower. Participants in the highest NT-proBNP group had 5.72-fold higher odds of CKD compared to the lowest group.\n\nIn longitudinal analysis of 4,205 individuals, higher baseline NT-proBNP predicted faster eGFR decline: -1.37 ml/min/1.73m² per 1 SD increase over 10 years, and higher CKD incidence. Associations were stronger in participants with existing cardiovascular disease and diabetes, suggesting the heart-kidney peptide connection is especially important in these high-risk populations.","whyItMatters":"Chronic kidney disease is often called a 'silent disease' because kidney function can decline significantly before symptoms appear. Finding that routinely measured heart peptides can predict kidney decline means clinicians could identify at-risk patients earlier using tests they may already be ordering. This is especially valuable for patients with heart disease or diabetes, who are at high risk for both cardiac and kidney complications.","specificNumbers":"","methodology":"This was a large observational study within the BiomarCaRE project, a European multi-cohort collaboration. Cross-sectional analyses included up to 61,830 participants with measurements of MR-proADM, MR-proANP, and NT-proBNP. Longitudinal analysis followed 4,205 individuals with NT-proBNP data over approximately 10 years. Kidney function was assessed using eGFR calculated from creatinine, cystatin C, or both. Markers were categorized into four groups for dose-response analysis. Models were adjusted for cardiovascular risk factors.","limitations":"The longitudinal analysis was limited to NT-proBNP only and included a smaller subset (4,205 of 61,830). As an observational study, it cannot prove that elevated cardiac peptides cause kidney decline — both may reflect shared risk factors. Different cohorts within BiomarCaRE used different eGFR equations and collection methods. The study did not test whether interventions that lower natriuretic peptide levels also protect kidney function."},{"rthcId":"RPEP-15566","title":"Modulating synovial macrophage responses to nociceptive signals attenuates inflammation in rheumatoid arthritis.","authors":"Lin, Lan; Chen, Yang; Lin, Yiming; Yuan, Xuhui; Huang, Jiexin; Cai, Yuanqing; Zhang, Canhong; Li, Hongyan; Zhang, Chaofan; Lin, Huangfeng; Wu, Baijian; Lv, Jianhua; Yu, Shaolin; Liao, Yuntao; Wu, Zhaoyang; Li, Wenbo; Zhang, Zeyu; Lin, Jianhua; Chang, Cheng; Yang, Bin; Zhang, Wenming; Fang, Xinyu","year":2026,"journal":"Molecular therapy : the journal of the American Society of Gene Therapy, 34(3), 1813-1835","doi":"10.1016/j.ymthe.2025.11.028","pmid":"41311059","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15567","title":"Ocular Complications of SGLT-2 Inhibitors, GLP-1 Receptor Agonists, and DPP-4 Inhibitors in T2DM Treatments: A Retrospective Real-World Cohort Study.","authors":"Lin, Lee-Yuan; Wu, Jie-Syuan; Jeng, Wei-Jung; Tsai, Chen-Hsin; Sun, Jia-Wei; Kuo, Cheng-Hao; Yuliani, Fara Silvia; Lin, Shyh-Hsiang","year":2026,"journal":"Clinical pharmacology and therapeutics, 119(1), 255-266","doi":"10.1002/cpt.70087","pmid":"41074575","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15568","title":"Glucagon-like Peptide-1 Receptor Dependent Signaling in Cardiovascular Health and Disease: A Mini-review.","authors":"Lin, Meng-Piao; Xue, Bing-Jie; Bai, Xiao-Jie","year":2026,"journal":"Journal of cardiovascular translational research, 19(1)","doi":"10.1007/s12265-026-10759-7","pmid":"41724871","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15569","title":"Whole-genome sequencing and comparative genomics reveal antimicrobial potential and adaptive traits of Bacillus velezensis AM12.","authors":"Lin, Qianqian; Pan, Fengzhi; Yang, JinJin; Pan, Ruixue; Ma, Haotian; Wu, Shiyun; Jia, Mingyuan; Xu, Huayuan; Wu, Jingchun; Peng, Jinju; Ding, Yuexia; Guo, Fucheng; Ma, Yi","year":2026,"journal":"Functional & integrative genomics, 26(1), 27","doi":"10.1007/s10142-025-01806-8","pmid":"41546830","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15570","title":"Antimicrobial peptide LRSG08 from Penaeus vannamei exhibits antibacterial activity against Vibrio spp. in aquatic products.","authors":"Lin, Rong; Feng, Bo; Wang, Mingyao; Aweya, Jude Juventus; Liang, Duo; Jin, Ritian; Weng, Wuyin; Yang, Shen","year":2026,"journal":"Microbial pathogenesis, 213, 108330","doi":"10.1016/j.micpath.2026.108330","pmid":"41619987","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"LRSG08 (sequence: GITIQCILPGFVVSKLSKLK) demonstrated potent antibacterial activity with MIC values of 2 μg/mL against V. parahaemolyticus and V. alginolyticus, and 125 μg/mL against V. vulnificus. Over 80% bacterial killing was achieved within 2.5 hours.\n\nMechanism of action studies revealed that LRSG08 selectively accumulates on the V. parahaemolyticus cell surface, disrupts membrane integrity causing nucleic acid leakage, and exhibits concentration-dependent binding to genomic DNA. In vivo, LRSG08 significantly increased zebrafish survival from V. parahaemolyticus infection to 80% at 72 hours. Safety profiling showed the peptide is nonhemolytic and has low cytotoxicity in vitro.","whyItMatters":"Vibrio species are the leading cause of seafood-associated bacterial gastroenteritis worldwide, and V. vulnificus can cause fatal wound infections. Antibiotic resistance in Vibrio is increasing, and conventional antibiotics in aquaculture contribute to resistance development. An antimicrobial peptide derived from the shrimp's own immune system offers a natural, potentially resistance-resistant alternative for both food safety and aquaculture disease prevention — with the added benefit of being nonhemolytic and low-toxicity.","specificNumbers":"","methodology":"The peptide was identified from Penaeus vannamei (white shrimp) using ultra-performance liquid chromatography-mass spectrometry and bioinformatics. Antibacterial activity was determined by MIC assays against three Vibrio species. Time-kill kinetics were measured over 2.5 hours. Mechanism studies used fluorescence microscopy to visualize membrane accumulation, membrane integrity assays to detect nucleic acid leakage, and DNA binding assays. In vivo efficacy was tested in zebrafish challenged with V. parahaemolyticus. Safety was assessed by hemolysis and cytotoxicity assays.","limitations":"The in vivo model used zebrafish rather than a mammalian system, so efficacy in human Vibrio infections cannot be inferred. The MIC against V. vulnificus (125 μg/mL) was substantially higher than against the other two species, suggesting limited activity against this particularly dangerous pathogen. Peptide stability in serum, gastric conditions, and at various temperatures relevant to food preservation was not assessed. Manufacturing scalability and cost were not addressed. Long-term resistance development was not studied."},{"rthcId":"RPEP-15571","title":"Comparison of the renal outcomes of novel antidiabetic agents in patients with type 2 diabetes with chronic kidney disease: A systematic review and network meta-analysis of randomized controlled trials.","authors":"Lin, Rong; Hsu, Chia-Li; Shih, Ming-Chieh; Chien, Kuo-Liong; Wu, Hon-Yen","year":2026,"journal":"Diabetes, obesity & metabolism, 28(1), 518-528","doi":"10.1111/dom.70224","pmid":"41147324","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15572","title":"Optimized TPL6 Peptide Gel Exhibits Broad-Spectrum Antimicrobial Activity and Effectively Treats Drug-Resistant Wound Infections in Diabetic Mice.","authors":"Lin, Wen-Chun; You, Ming-Feng; Chen, Yun-Ru; Chen, Jyh-Yih","year":2026,"journal":"Advanced healthcare materials, 15(8), e03863","doi":"10.1002/adhm.202503863","pmid":"41273059","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15573","title":"Honokiol attenuates diabetes by enriching Akkermansia muciniphila andregulating tryptophan metabolism in mice.","authors":"Lin, Yang; Jiang, Zhengmeng; Yu, Zhilu; Huang, Tianqing; Gui, Wanyu; Wang, Ziyuan; Li, Fei; Xiao, Pingting; Li, Changyin; Liu, Ehu","year":2026,"journal":"Chinese journal of natural medicines, 24(1), 59-72","doi":"10.1016/S1875-5364(26)61077-1","pmid":"41571367","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15574","title":"Integrating gepants into clinical practice for the acute treatment of migraine.","authors":"Lipton, Richard B; Dodick, David W; Davis, Linda; Nahas, Stephanie J; Goadsby, Peter J","year":2026,"journal":"Headache","doi":"10.1111/head.70047","pmid":"41709494","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15575","title":"Treatment effectiveness of galcanezumab versus traditional oral migraine preventive medications at 3 months: Results from the TRIUMPH study.","authors":"Lipton, Richard B; Láinez, Miguel J A; Ahmed, Zubair; Vallarino, Carlos; Novick, Diego; Vincent, Maurice; Viktrup, Lars; Robinson, Rebecca L","year":2026,"journal":"Headache, 66(3), 604-614","doi":"10.1111/head.15045","pmid":"41017292","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15576","title":"GTS-21 Alleviates Acute Lung Injury by Enhancing GLP-1 Secretion and Regulating Alveolar Surfactant Proteins via α7nAChR Activation.","authors":"Liu, Chunli; Song, Yuqi; Tian, Xinghan; Quan, Hongkun; Tian, Weikun; Taneja, Niitiggya; Wang, Guirong; Meng, Qinghe; Cooney, Robert N","year":2026,"journal":"Inflammation, 49(1), 58","doi":"10.1007/s10753-026-02455-0","pmid":"41563607","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15577","title":"The role of PYY in improving insulin resistance.","authors":"Liu, Chunyan; Ren, Na; Zhang, Haixin; Ma, Jian","year":2026,"journal":"Frontiers in endocrinology, 17, 1784709","doi":"10.3389/fendo.2026.1784709","pmid":"41788781","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"PYY deficiency is closely linked to insulin resistance development. The two circulating forms have distinct roles: PYY(3-36) acts primarily through Y2 receptors in the hypothalamus (suppressing appetite) and in peripheral tissues (adipose, skeletal muscle, liver) to enhance insulin sensitivity. PYY(1-36) acts through Y1 receptors to protect pancreatic beta cells and fine-tune insulin secretion. PYY(3-36) also promotes weight loss by delaying gastric emptying, indirectly improving insulin resistance through weight reduction. The review identifies PYY as playing an important role in glucose homeostasis.","whyItMatters":"While GLP-1 drugs have dominated the metabolic drug landscape, PYY represents another gut peptide with significant therapeutic potential that's less developed. Understanding PYY's dual mechanisms — central appetite suppression and peripheral insulin sensitization — could lead to new drug candidates or combination therapies. PYY-based treatments could complement GLP-1 drugs by targeting different receptor systems and metabolic pathways, potentially enhancing overall treatment effectiveness.","specificNumbers":"","methodology":"Narrative review synthesizing published research on PYY biology, receptor signaling (Y1R, Y2R), and effects on insulin sensitivity across multiple tissues. Covers both basic science research on PYY mechanisms and clinical/translational studies exploring PYY's therapeutic potential for insulin resistance and metabolic diseases.","limitations":"This is a narrative review without systematic methodology or meta-analysis. PYY-based therapies remain largely preclinical, with limited human clinical trial data. The relative contribution of PYY's appetite-suppressing versus direct insulin-sensitizing effects is difficult to disentangle. The review doesn't address potential adverse effects of PYY-based therapies or challenges in drug development (stability, delivery, dosing)."},{"rthcId":"RPEP-15578","title":"African swine fever virus-encoded protein MGF 505-3R impairs innate immunity via ubiquitin-mediated degradation of MyD88.","authors":"Liu, Hongzhi; Sun, Likang; Wang, Fangyu; Huang, Xia; Huang, Jingyi; Kang, Xilong; Gu, Dan; Song, Li; Meng, Chuang; Xiong, Dan; Jiao, Xinan; Pan, Zhiming","year":2026,"journal":"Communications biology","doi":"10.1038/s42003-026-09681-0","pmid":"41673114","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15579","title":"Semaglutide attenuates autistic-like behaviors in BTBR mice through the shaping of gut microbiota.","authors":"Liu, Jiayin; Liu, Tianyao; Nie, Lina; Zhou, Lianyu; Luo, Jing; Guo, Li; Zhang, Xinggao; Gong, Meifeng; Chen, Zhenyang; Li, Xin; Fan, Xiaotang","year":2026,"journal":"Pharmacological research, 225, 108149","doi":"10.1016/j.phrs.2026.108149","pmid":"41724218","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15580","title":"Sensory Nerve-Derived CGRP Controls Osteoclastogenesis by Limiting Macrophage Bioenergetics in Bone Repair.","authors":"Liu, Jiaying; Zhang, Ting; Mu, Yuqing; Li, Lili; Jin, Ju; Dudley, Kevin J; Gao, Wendong; Cai, Donglin; Yan, Fuhua; Xiao, Lan; Xiao, Yin","year":2026,"journal":"Advanced science (Weinheim, Baden-Wurttemberg, Germany), e18303","doi":"10.1002/advs.202518303","pmid":"41764371","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15581","title":"Expanding the chemical space of peptides via biocompatible tryptophan C7-arylation.","authors":"Liu, Lei; Zhao, Yanyang; Su, Yiming; Wang, Boning; Xiong, Yue; Wang, Tianhang; Hua, Xiude; Ye, Yonghao; Shi, Zhuangzhi; Wang, Huan","year":2026,"journal":"Chemical science","doi":"10.1039/d5sc08312e","pmid":"41567964","tags":[],"studyType":"laboratory","evidenceStrength":"low","keyFinding":"A new chemical method for modifying tryptophan residues in peptides at a specific position (C7) was developed using rhodium catalysis. When applied to antimicrobial peptides, this modification dramatically enhanced antifungal activity against Aspergillus fumigatus by up to 49-fold over the unmodified parent peptide.\n\nThe modified tryptophan residues also functioned as fluorescent probes with environment-sensitive, turn-on fluorescence, enabling wash-free imaging of bacterial cells. The method showed broad substrate compatibility, excellent selectivity, and high functional group tolerance.","whyItMatters":"Fungal infections, particularly Aspergillus, are a growing threat to immunocompromised patients with limited treatment options. This chemical tool enables precise modification of existing antimicrobial peptides to make them dramatically more potent, potentially opening new avenues for antifungal drug development. The dual imaging capability also helps track where peptides go in biological systems.","specificNumbers":"Up to 49-fold improvement in antifungal activity · C7-selective arylation · Rh-catalyzed · Removable directing group · Turn-on fluorescence · Aspergillus fumigatus target","methodology":"Chemical synthesis study developing rhodium-catalyzed, P(III)-directed C7-selective arylation of tryptophan using a removable N-PtBu2 auxiliary. Substrate scope, regioselectivity, and functional group tolerance were characterized. Modified residues were incorporated into antimicrobial peptides and tested for antifungal activity against A. fumigatus. Fluorescence properties were evaluated for bacterial cell imaging.","limitations":"This is a chemistry/methods study demonstrating a new modification technique. The antifungal testing was limited to A. fumigatus in vitro. No in vivo toxicity, pharmacokinetics, or animal infection model data were presented. The 49-fold activity enhancement is specific to particular peptide-modification combinations and may not generalize to all antimicrobial peptides."},{"rthcId":"RPEP-15582","title":"Effective combinatorial antifungal therapy using a host defense peptide mimic that self-assembles into delivery micelles.","authors":"Liu, Longqiang; Zhou, Min; Xiao, Ximian; Cong, Zihao; Wu, Yueming; Xie, Jiayang; Zhang, Qiang; Zhang, Junyu; Jiang, Weinan; Liu, Runhui","year":2026,"journal":"Nature biotechnology","doi":"10.1038/s41587-025-02930-3","pmid":"41482540","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15583","title":"Rational β-turn engineering of a disulfide-free β-hairpin-like antimicrobial peptide W2PG with enhanced stability, selectivity, and in vivo efficacy.","authors":"Liu, Meng; Jiang, Peng; Ruan, Binghui; Cui, Yunfei; Zhang, Junjie; Ye, Yuxiu; Zhangsun, Dongting; Luo, Sulan; Wu, Yong","year":2026,"journal":"Bioorganic chemistry, 173, 109612","doi":"10.1016/j.bioorg.2026.109612","pmid":"41690116","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Using a β-turn engineering strategy, researchers designed a short antimicrobial peptide called W2PG that achieved broad-spectrum antibacterial activity (MIC 4–8 μM) with low hemolysis and cytotoxicity, plus improved protease and serum stability over typical AMPs. The peptide kills bacteria by disrupting their membranes through concentration-dependent permeabilization and depolarization.\n\nIn mouse infection models, W2PG performed comparably to polymyxin B — a last-resort antibiotic — without observable organ toxicity, demonstrating real in vivo therapeutic potential.","whyItMatters":"Antimicrobial resistance is projected to kill 10 million people annually by 2050, and new antibiotics are desperately needed. Antimicrobial peptides have long been promising but have been held back by instability and toxicity. This study shows that rational structural engineering — specifically designing β-hairpin folds — can overcome these barriers, creating peptides that are stable, safe, and effective enough to match existing clinical antibiotics in animal models.","specificNumbers":"","methodology":"The researchers used rational peptide design incorporating a Pro-Gly motif and aromatic residues to create a β-hairpin-like structure. They tested W2PG's antibacterial spectrum via minimum inhibitory concentration (MIC) assays, assessed safety through hemolysis and cytotoxicity tests, measured stability against proteases and serum, performed membrane disruption studies, ran molecular dynamics simulations, and evaluated efficacy in murine infection models compared to polymyxin B.","limitations":"The study tested W2PG in mouse models only — human clinical trials have not been conducted. The specific bacterial species and infection models tested are not detailed in the abstract. Long-term toxicity, pharmacokinetic profile, and resistance development potential over extended use were not assessed. Manufacturing scalability was not addressed."},{"rthcId":"RPEP-15584","title":"Dual Function Characterisation of the 4-Cysteine Hepcidin in the Antarctic Toothfish Dissostichus mawsoni.","authors":"Liu, Mingli; Hu, Ruiqin; Zhai, Wanying; Yang, Jihui; Ma, Jingwen; Hu, Peng; Xu, Qianghua; Chen, Liangbiao","year":2026,"journal":"Journal of fish diseases, e70142","doi":"10.1111/jfd.70142","pmid":"41723628","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15585","title":"Exenatide attenuates neuroinflammation and rescues sepsis-induced depressive behavior and cognitive dysfunction in a mouse model.","authors":"Liu, Shenhai; Chen, Qiao; Liu, Hui; Chen, Zihang; Ding, Na; Sun, Tao; Wang, Lin","year":2026,"journal":"Neuroscience, 600, 112-129","doi":"10.1016/j.neuroscience.2026.02.033","pmid":"41747818","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15586","title":"Luteolin-Loaded TGN/RAP12 Dual-Peptide Functionalized Nanoparticles: Synergistic Enhancement of BBB Penetration and Microglia Targeting in Alzheimer's Disease.","authors":"Liu, Shumeng; Xing, Yue; Na, Yue; Wu, Hao; Liu, Chi; Wang, Zhigang; Zhang, Ning; Wu, Xiuhong; Geng, Fang","year":2026,"journal":"Molecules (Basel, Switzerland), 31(4)","doi":"10.3390/molecules31040671","pmid":"41752448","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15587","title":"Association between tirzepatide use and risk of mortality, hospitalization, and suicidal behavior in patients with schizophrenia spectrum disorders: A one-year retrospective cohort study of 3618 patients.","authors":"Liu, Ting-Hui; Hsu, Chia-Hsuan; Wu, Jheng-Yan; Huang, Po-Yu; Chang, Chih-Cheng; Lai, Chih-Cheng","year":2026,"journal":"European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 103, 112739","doi":"10.1016/j.euroneuro.2025.11.016","pmid":"41389474","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15588","title":"Electroacupuncture modulates myocardial insulin signaling and inflammatory markers in a rat model of type 2 diabetes.","authors":"Liu, Xiao-Xiao; Zhang, Hai-Hua; Sun, Jian; Chen, Xiao-Zhuan; Ye, Yang-Yang; Quan, Jing-Yi; Zhang, Lu; Nie, Lin-Lin; Li, Min; Li, Zhi-Xing","year":2026,"journal":"Acupuncture in medicine : journal of the British Medical Acupuncture Society, 44(1), 36-48","doi":"10.1177/09645284251399239","pmid":"41320887","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15589","title":"The VIP-VIPR2 axis strengthens intestinal barrier integrity and antimicrobial immunity in Ctenopharyngodon idella.","authors":"Liu, Xiaofeng; Hou, Qian; Zhou, Zejun","year":2026,"journal":"Developmental and comparative immunology, 174, 105539","doi":"10.1016/j.dci.2025.105539","pmid":"41412434","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15590","title":"Screening and application of a coagulation peptide-KFVLK with rapid hemostatic property.","authors":"Liu, Xin; Ren, Zekai; Ding, Xin; Wu, Han; Wang, Yumei; Cao, Yang; Cong, Hailin; Yu, Bing","year":2026,"journal":"Colloids and surfaces. B, Biointerfaces, 260, 115387","doi":"10.1016/j.colsurfb.2025.115387","pmid":"41447860","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15591","title":"Discovery and identification of semaphorin 4D as a bioindicator of high fracture incidence in type 2 diabetic mice with glucose control.","authors":"Liu, Xuanchen; Wang, Mo; Xu, Bin; Ma, Xue; Jiang, Yangzi; Huang, Hai; Shi, Zengzeng; Wu, Hao; Wu, Zhigang; Guo, Shuo; Zhao, Jungang; Zhao, Jian; Li, Xiaokang; Liang, Li; Guo, Zheng; Shi, Lei; Sun, Chao; Wang, Ning","year":2026,"journal":"Journal of advanced research, 79, 179-195","doi":"10.1016/j.jare.2025.03.014","pmid":"40073972","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Sema4D was identified as the key regulator of bone fragility in type 2 diabetes through proteomics and deep screening analysis. Exendin-4 (a GLP-1 receptor agonist) improved bone biomechanical properties by decreasing serum Sema4D levels and promoting osteogenesis via CRMP2 activation. Metformin had minimal direct effect on Sema4D but enhanced exendin-4's action through a miR-140-3p-STAT3-miR-3657 signaling cascade that increased GLP-1 receptor expression. Anti-Sema4D treatment alone improved bone strength comparably to the combination of metformin and exendin-4. Blood glucose control was not the primary factor in bone remodeling.","whyItMatters":"Fractures in diabetic patients are a major and growing clinical problem. Despite good blood sugar control, these patients continue to break bones because the underlying bone quality issue isn't about glucose — it's about Sema4D. This study provides both a diagnostic biomarker (blood Sema4D levels) and a therapeutic mechanism (GLP-1 peptide-mediated Sema4D reduction) that could guide fracture prevention in the hundreds of millions of people with type 2 diabetes.","specificNumbers":"","methodology":"Multi-technique study in T2DM mice using micro-CT for bone mass analysis, three-point bending for biomechanical strength, ELISA for protein expression, proteomics and deep screening for pathway discovery, immunoprecipitation-mass spectrometry for protein interactions, and dual-luciferase reporter assays for molecular signaling validation.","limitations":"This is an animal study in diabetic mice, and results may not translate directly to human bone biology. The specific doses and treatment durations in mice may not correspond to clinical dosing. Anti-Sema4D treatment is not currently available as a clinical therapy. The study uses exendin-4 rather than clinically dominant GLP-1 drugs like semaglutide, and effects may differ between agents."},{"rthcId":"RPEP-15592","title":"Single-dose pharmacokinetics of sublingual semaglutide in rats.","authors":"Liu, Yi; Song, Guiyun; Banov, Daniel; Denison, Jennifer; Davis, Courtaney; Ip, Kendice","year":2026,"journal":"European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 217, 107406","doi":"10.1016/j.ejps.2025.107406","pmid":"41386332","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15593","title":"Skeletal Effect of Semaglutide and Tirzepatide in Patients with Increased Risk of Fractures.","authors":"Liu, Yi; Walzer, Dalia; Schmitz, Sarah; Shukla, Alpana P; Ma, Xiaoyue; Chirko, Dawn; Pipia, Ilissa; Sathi, Swetha; Shukairy, Uthman; Greenberg, Michael; Kashyap, Sangeeta R; Stein, Emily M","year":2026,"journal":"The Journal of clinical endocrinology and metabolism","doi":"10.1210/clinem/dgag052","pmid":"41655226","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15594","title":"A short antimicrobial peptides family demonstrates efficacy to infection via a multimodal mechanism of action.","authors":"Liu, Yifan; Cui, Pengfei; Sun, Jingyi; Ru, Shaoguo","year":2026,"journal":"Antimicrobial agents and chemotherapy, 70(2), e0134325","doi":"10.1128/aac.01343-25","pmid":"41433402","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15595","title":"Modulating Purothionin Accumulation and Signal Peptide Cleavage Fine-Tunes Wheat Flour Gluten Properties to Improve Cookie-Making Quality.","authors":"Liu, Yijie; Chang, Siyuan; Zhang, Zhaoheng; Kang, Tianqi; Liu, Mingde; Zong, Yuan; Ni, Fei; Bao, Yinguang; Zhang, Ruijie; Zhang, Xiaobang; Du, Jinkun; Xin, Mingming; Hu, Zhaorong; Liu, Jie; Ni, Zhongfu; Sun, Qixin; Yao, Yingyin","year":2026,"journal":"Advanced science (Weinheim, Baden-Wurttemberg, Germany), e12581","doi":"10.1002/advs.202512581","pmid":"41498695","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15596","title":"Untargeted Metabolomics Reveals Shared and Unique Metabolites in Bifidobacterium and Lactobacillus Derived Postbiotics.","authors":"Liu, Yue; Sun, Yuhang; Fang, Bing; Wang, Ran; Lan, Hanglian; Zhao, Wen; Hung, Wei-Lian; Zhao, Liang; Zhang, Ming","year":2026,"journal":"Journal of agricultural and food chemistry, 74(3), 2749-2760","doi":"10.1021/acs.jafc.5c10317","pmid":"41407504","tags":["bioactive-peptides"],"studyType":"laboratory","evidenceStrength":"moderate","keyFinding":"An untargeted metabolomic analysis of 14 probiotic strains identified 3,333 metabolites in their cell-free supernatants (postbiotics), with 1,262 metabolites shared across all strains. Bifidobacterium postbiotics contained significantly higher amino acid and peptide content (48.44%) compared to Lactobacillus, with glutamic acid peptides being particularly prevalent.\n\nIndole derivatives — compounds important for immune regulation through the aryl hydrocarbon receptor — were found in all strains, but their types differed: 3-indoleacrylic acid was more concentrated in Lactobacillus, while indole-3-lactic acid was more prevalent in Bifidobacterium. These findings suggest different probiotic species produce distinct bioactive peptide and metabolite profiles.","whyItMatters":"Postbiotics — the beneficial substances produced by probiotic bacteria — are gaining attention as a way to deliver health benefits without requiring live bacteria. This study provides the first detailed metabolic fingerprint comparing what Bifidobacterium and Lactobacillus actually produce, revealing that the peptide and amino acid profiles differ substantially between these two major probiotic families. Understanding these differences could help researchers design more targeted probiotic or postbiotic therapies.","specificNumbers":"14 probiotic strains · 3,333 metabolites identified · 1,262 shared across all strains · 62.5% linked to microbial metabolism · 48.44% amino acid/peptide content in Bifidobacterium CFS","methodology":"The researchers grew 14 different probiotic strains (from Bifidobacterium and Lactobacillus families) and collected their cell-free supernatants — essentially the liquid left after removing the bacteria. They then used untargeted metabolomics to identify and compare all the small molecules, peptides, and other metabolites produced by each strain, using principal component analysis to map the differences.","limitations":"This was an in vitro laboratory analysis — the metabolites were identified in culture conditions, not in the human gut. Whether these same peptides and metabolites are produced in meaningful amounts inside the body remains unknown. The study also did not test the biological activity of the identified peptides, only their presence."},{"rthcId":"RPEP-15597","title":"Glucagon-like Peptide-1 receptor agonists as emerging therapeutics in bipolar disorder: a narrative review of preclinical and clinical evidence.","authors":"Llach, Cristian-Daniel; Badulescu, Sebastian; Tabassum, Aniqa; Shah, Hiya; Gill, Hartej; Le, Gia Han; Vieta, Eduard; McIntyre, Roger S; Rosenblat, Joshua D; Mansur, Rodrigo B","year":2026,"journal":"Molecular psychiatry, 31(1), 456-479","doi":"10.1038/s41380-025-03261-0","pmid":"40940560","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15598","title":"Acute Pancreatitis Associated With Semaglutide in a Patient With Multimorbidity: A Case Report.","authors":"Lo, Shao Chi; Yeh, Hsing Jung","year":2026,"journal":"Cureus, 18(1), e101908","doi":"10.7759/cureus.101908","pmid":"41728571","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15599","title":"Impacts of ketogenic diet intervention on cardiometabolic outcomes in obese, dysglycemic mice.","authors":"Locatelli, Cassandra A A; Nguyen, My-Anh; Morrow, Nadya M; Cameron, Elena; Trzaskalski, Natasha A; Lorenzen-Schmidt, Ilka; Morissette, Arianne; Mulvihill, Erin E","year":2026,"journal":"Cardiovascular diabetology, 25(1), 34","doi":"10.1186/s12933-025-03046-3","pmid":"41484888","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15600","title":"Selectivity Modulation of Small Cationic Membrane-Active Cyclic Peptides with Broad-Spectrum Activity against Bacteria and Fungi.","authors":"Lohan, Sandeep; Tiwari, Rakesh Kumar; Maslennikov, Innokentiy; Das Gupta, Kaustav; Singh, Shakti; Parang, Keykavous","year":2026,"journal":"Journal of medicinal chemistry","doi":"10.1021/acs.jmedchem.5c03707","pmid":"41755744","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15601","title":"Sacubitril/Valsartan vs Enalapril in Heart Failure Due to Chagas Disease: An Open-Label, Multicenter Randomized Clinical Trial.","authors":"Lopes, Renato D; Bocchi, Edimar Alcides; Echeverría, Luis Eduardo; Demacq, Caroline; de Barros E Silva, Pedro Gabriel Melo; Barbosa, Lilian Mazza; Damiani, Lucas; Sayyed, Sarfaraz; Yoshida, Liandra A F; Furtado, Remo Holanda M; Morillo, Carlos A; Kevorkian, Ruben; Ramires, Felix; Bahit, M Cecilia; Magaña, Antonio; Chávez-Mendoza, Adolfo; Miguel da Silva, Adegil Henrique; Coelho da Silva, Aguinaldo; Freitas, Aguinaldo F; Romano, Alfredo Alejandro; Parneix, Anne; Segura, Armando; França, Cesar Cassio Broilo; Botta, Cristian Edgardo; de Barros, Edileide; Perna, Eduardo Roque; Montenegro, Eleonora; Quiroz Diaz, Franklin Roberto; Feitosa-Filho, Gilson Soares; Severini, Graciela Viviana; Molina, Israel; Miranda, Jacqueline Dos Santos Sampaio; Sala, Jorgelina; Kerr Saraiva, José Francisco; Carbajales, Justo; Maia, Lilia Nigro; Santana Passos, Luiz Carlos; Simões, Marcus Vinicius; Moreira, Maria da Consolação V; Nunes, Maria Carmo P; Hernandes, Mauro Esteves; Hominal, Miguel; Zarandon, Raquel Saa; Leon de la Fuente, Ricardo; Aras, Roque; Bazan, Silméia Garcia Zanati; Luiz da Silva, Telêmaco; Madrini, Vagner; de Oliveira, Wilson Alves; Saporito, Wladmir Faustino; Gimpelewicz, Claudio; McMurray, John J V","year":2026,"journal":"JAMA, 335(1), 49-59","doi":"10.1001/jama.2025.19808","pmid":"41335448","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15602","title":"Regulation of Aldosterone Secretion by Substance P and the Neurokinin Type 1 Receptor in Aldosterone-Producing Adenomas.","authors":"Lopez, Antoine-Guy; Duparc, Céline; Renouf, Sylvie; D'Agostino, Margot; De Sousa, Kelly; Amar, Laurence; Defortescu, Guillaume; Manceau, Gilles; Sabourin, Jean-Christophe; Fernandes-Rosa, Fabio Luiz; Zennaro, Maria-Christina; Meatchi, Tchao; Nicolas, Gaël; Louiset, Estelle; Lefebvre, Hervé","year":2026,"journal":"Journal of the American Heart Association, 15(2), e045539","doi":"10.1161/JAHA.125.045539","pmid":"41532541","tags":[],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Substance P (SP) nerve fibers were found in 90% of aldosterone-producing adenomas (APAs) examined, and the neurokinin 1 receptor (NK1R) was strongly expressed in these tumors. Functional experiments showed that SP stimulated aldosterone secretion in 6 out of 10 APA cultures. The NK1R antagonist aprepitant — an already approved drug — blocked SP-induced aldosterone secretion in 3 of 4 responsive cultures tested.\n\nIn perifused tissue explants, SP also influenced aldosterone pulsatility, enhancing overall mineralocorticoid output. These results suggest the SP-NK1R pathway may be a druggable target for treating primary aldosteronism in a subset of patients.","whyItMatters":"Primary aldosteronism is the most common cause of secondary hypertension, and aldosterone-producing adenomas are a major driver. Current treatment options are limited to surgery or lifelong mineralocorticoid receptor antagonists. Identifying a new signaling pathway (SP-NK1R) that drives excess aldosterone production opens the door to targeted pharmacological treatment — potentially using aprepitant, a drug already FDA-approved for other purposes, which could accelerate clinical translation.","specificNumbers":"n=56 APA tissues · SP nerve fibers in 90% of tumors · SP stimulated aldosterone in 6/10 cultures · Aprepitant blocked secretion in 3/4 responsive cultures","methodology":"The researchers analyzed 56 aldosterone-producing adenoma tissue samples using molecular biology, immunohistochemistry, and functional techniques. They mapped SP-positive nerve fibers and NK1R expression within and around adenomas. Functional studies used cultured APA cells and perifused tissue explants to measure aldosterone secretion in response to SP stimulation and NK1R blockade with aprepitant.","limitations":"This is an in vitro study using excised tumor tissue — results may not directly predict drug responses in living patients. SP stimulated aldosterone in only 60% of cultures tested (6/10), and aprepitant was only tested on 4 responsive cultures, limiting generalizability. The variability in response suggests the SP-NK1R pathway is relevant in a subset, not all, APA patients."},{"rthcId":"RPEP-15603","title":"Mechanisms and clinical implications of gut-brain interactions.","authors":"Lorsch, Zachary S; Liddle, Rodger A","year":2026,"journal":"The Journal of clinical investigation, 136(1)","doi":"10.1172/JCI196346","pmid":"41480755","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies several key mechanisms of gut-brain communication:\n\n• A direct enteroendocrine cell-neural circuit that allows gut cells to signal the brain in real time\n• Microbiome-mediated pathways that influence brain function and behavior\n• Neuroimmune interactions linking gut inflammation to neurological and psychiatric conditions\n\nCritically, the review demonstrates that GLP-1 receptor agonists for obesity and guanylyl cyclase C agonists for irritable bowel syndrome achieve their therapeutic effects by acting on these gut-brain pathways — not just through local gut effects. This reframes how we understand these widely prescribed peptide drugs.","whyItMatters":"With millions of people now taking GLP-1 drugs like semaglutide and tirzepatide, understanding that these peptides work partly through gut-brain signaling pathways is crucial. This review provides the mechanistic framework explaining why GLP-1 drugs affect not just appetite and blood sugar, but also potentially mood, addiction, and neurological function — effects that have surprised both patients and clinicians.","specificNumbers":"","methodology":"This is a narrative review published in the Journal of Clinical Investigation. The authors synthesized findings from human and animal studies across gastroenterology, neurology, psychiatry, and endocrinology to describe mechanisms of gut-brain communication and their clinical implications. No original experimental data was generated.","limitations":"As a review article, this synthesizes existing research rather than generating new data. The authors' interpretation of the literature reflects their perspective and may emphasize certain pathways over others. Many of the mechanistic pathways described are based on animal studies that may not fully translate to humans. The rapidly evolving nature of microbiome and GLP-1 research means some conclusions may be refined by newer findings."},{"rthcId":"RPEP-15604","title":"Distinct Bomanins at the Drosophila 55C locus function in resistance and resilience to infections.","authors":"Lou, Yanyan; Zhang, Bo; Zhang, Zhiyuan; Pan, Yingyi; Yang, Jianwen; Li, Lu; Huang, Jianqiong; Yuan, Zihang; Liegeois, Samuel; Bulet, Philippe; Xu, Rui; Zi, Li; Ferrandon, Dominique","year":2026,"journal":"EMBO reports, 27(3), 629-653","doi":"10.1038/s44319-025-00559-6","pmid":"41513836","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15605","title":"JNK3 regulates β cell responses to incretins in human islets and mouse models.","authors":"Louzada, Ruy A; Gonzalez Medina, Marel; Pita-Grisanti, Valentina; Bouviere, Jessica; Neves, Amanda F; Almaça, Joana; Han, Myoung Sook; Davis, Roger J; Leibowitz, Gil; Blandino-Rosano, Manuel; Bernal-Mizrachi, Ernesto","year":2026,"journal":"The Journal of clinical investigation, 136(1)","doi":"10.1172/JCI185707","pmid":"41480766","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15606","title":"Loading of therapeutic cell penetrating peptides into extracellular vesicles for pulmonary fibrosis.","authors":"Lowe, Neona M; Nguyen, Bryan B; Mizenko, Rachel R; Trushchankova, Anastasia; Hadley, Dustin J; Panitch, Alyssa; Carney, Randy P","year":2026,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 390, 114561","doi":"10.1016/j.jconrel.2025.114561","pmid":"41423070","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15607","title":"Mechanical forces from intercellular peptide self-assembly drive spheroid formation.","authors":"Lu, Honglei; Li, Yaoting; Yang, Xuejiao; Wu, Bihan; Kong, Deling; Li, Chen; Wang, Huaimin; Feng, Zhaoqianqi","year":2026,"journal":"Nature communications, 17(1), 1801","doi":"10.1038/s41467-026-68513-1","pmid":"41587977","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15608","title":"Proteomic profiling of Monascus-fermented djulis (Chenopodium formosanum) identifies ACE-inhibitory peptides through integrated in silico and in vitro approaches.","authors":"Lu, Jheng-Jhe; Cheng, Kuan-Chen; Khumsupan, Darin; Hsieh, Chen-Che; Hsieh, Chang-Wei; Santoso, Shella Permatasari; Angkawijaya, Artik Elisa; Kuo, Hsing-Chun","year":2026,"journal":"Food chemistry, 500, 147474","doi":"10.1016/j.foodchem.2025.147474","pmid":"41401482","tags":["ace-inhibitory-peptides","food-derived-peptides"],"studyType":"in-vitro","evidenceStrength":"preliminary","keyFinding":"Researchers identified ACE-inhibitory peptides produced during fermentation of djulis (a Taiwanese grain) with Monascus purpureus (red yeast). The protein hydrolysates from fermented dehulled djulis achieved 40.71% ACE inhibition by day 8 — approaching the 43.33% inhibition achieved by captopril, a widely prescribed blood pressure drug.\n\nUsing computational screening and proteomics, they identified a 9-amino-acid peptide called DK9 (DAAGYVADK) as the lead candidate. Molecular docking showed DK9 binds ACE with a binding affinity of -9.174 kcal/mol, stronger than captopril's -5.77 kcal/mol. DK9 works as a competitive inhibitor, and computational safety profiling predicted low toxicity and favorable drug-like properties.","whyItMatters":"High blood pressure affects over a billion people worldwide, and ACE inhibitors are among the most commonly prescribed medications. Finding natural, food-derived ACE-inhibitory peptides could lead to functional foods or nutraceuticals that support blood pressure management with potentially fewer side effects than synthetic drugs. The discovery that fermented djulis produces a peptide nearly as effective as captopril in lab tests — with stronger binding affinity — makes it a noteworthy lead compound for further development.","specificNumbers":"40.71% ACE inhibition (vs. 43.33% for captopril) · DK9 peptide: DAAGYVADK · binding affinity: -9.174 kcal/mol (captopril: -5.77) · 7 hydrogen bonds with ACE active site · day 8 fermentation peak · competitive inhibition mechanism","methodology":"Djulis grain was fermented with Monascus purpureus, and protein hydrolysates were tested for ACE inhibition at various time points. The researchers used computational screening with the BIOPEP database and proteomics to identify candidate peptides. The lead peptide DK9 was evaluated through molecular docking simulation, enzyme kinetics analysis, and ADMET (absorption, distribution, metabolism, excretion, toxicity) computational profiling.","limitations":"This is entirely an in vitro and computational study — no animal or human testing was performed. ACE inhibition measured in a test tube does not necessarily translate to blood pressure reduction in living organisms, as the peptide must survive digestion, be absorbed, and reach the target enzyme. The comparison to captopril is based on in vitro inhibition percentages, not clinical efficacy. The ADMET predictions are computational estimates, not experimentally verified pharmacokinetic data."},{"rthcId":"RPEP-15609","title":"Glucagon-like peptide-1 and dual/triple receptor agonists in the treatment of metabolic dysfunction-associated steatotic liver disease: advances in mechanistic research.","authors":"Lu, Xinyi; Yang, Li","year":2026,"journal":"Frontiers in medicine, 13, 1763185","doi":"10.3389/fmed.2026.1763185","pmid":"41767516","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15610","title":"Antimicrobial peptide CATH-1 combats Streptococcus suis by targeting serine/threonine kinase.","authors":"Lu, Yi; Yu, Xiaoying; Pan, Yandi; Yin, Hang; Yang, Qingqing; Shen, Xin; Cao, Xuefeng; Li, Zhiwei; Peng, Lianci; Fang, Rendong","year":2026,"journal":"International journal of antimicrobial agents, 67(1), 107656","doi":"10.1016/j.ijantimicag.2025.107656","pmid":"41161580","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15611","title":"From Host-Derived Pressures to the Environmental Anti-Antimicrobial Peptides Resistome: Mechanisms, Reservoirs and Implications for Therapeutic Peptide Design.","authors":"Lu, Yi; Zhang, Baomei; Wang, Zishuo; He, Yidi; Ge, Hezi; Ma, Hongyue; Cui, Pengfei","year":2026,"journal":"Marine drugs, 24(2)","doi":"10.3390/md24020076","pmid":"41745479","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15612","title":"Efficacy of liraglutide on metabolic and reproductive outcomes in women with polycystic ovary syndrome: A systematic review and meta-analysis.","authors":"Lu, Yu-Ting; Chang, Po-Han; Chen, Hsuan-Ju; Hsueh, Ya-Wen; Chang, Chia-Wei; Hsu, Hsi-Chen; Yang, Tung-Chuan; Lin, Wu-Chou; Chang, Hsun-Ming","year":2026,"journal":"Diabetes, obesity & metabolism","doi":"10.1111/dom.70452","pmid":"41508932","tags":[],"studyType":"meta-analysis","evidenceStrength":"moderate","keyFinding":"In a meta-analysis of 7 RCTs (330 women with PCOS), liraglutide significantly improved both metabolic and reproductive outcomes: it increased menstrual frequency (g=1.76), reduced BMI (g=-0.52), improved insulin resistance (HOMA-IR g=-0.52), lowered luteinizing hormone and free androgen index, and modestly increased sex hormone-binding globulin. Adverse events were mainly mild GI symptoms. Ovulation and pregnancy outcomes could not be pooled due to insufficient data from the included trials.","whyItMatters":"PCOS affects 6-12% of reproductive-age women and causes both metabolic problems (insulin resistance, weight gain) and reproductive dysfunction (irregular periods, infertility). This meta-analysis provides the first pooled evidence that liraglutide addresses both dimensions simultaneously — improving insulin sensitivity and weight while also restoring menstrual regularity and improving hormonal balance.","specificNumbers":"7 RCTs · n=330 · Menstrual frequency: g=1.76, P<0.05 · BMI: g=-0.52 · HOMA-IR: g=-0.52 · LH ↓ · Free androgen index ↓ · SHBG ↑","methodology":"Systematic review and meta-analysis of RCTs comparing liraglutide (alone or combined) to placebo, metformin, or other active treatments in overweight/obese PCOS women. Six databases searched through May 2025. Random-effects model used. Results expressed as Hedges' g or odds ratios with 95% CIs.","limitations":"Small total sample of only 330 women across 7 trials. High heterogeneity for menstrual frequency outcome. Ovulation and pregnancy rates could not be analyzed due to insufficient reporting. Most studies likely used the 1.8 mg diabetes dose rather than the 3.0 mg weight loss dose. No long-term follow-up data."},{"rthcId":"RPEP-15613","title":"The use of semaglutide as an add-on therapy in patients with LADA.","authors":"Lunati, Maria Elena; Cimino, Vincenzo; Bernasconi, Davide; Romano, Cristina; Disoteo, Olga; Rossi, Antonio; Tinari, Camilla; Fiorina, Roberta Maria; Gandolfi, Alessandra; Morpurgo, Paola Silvia; D'Addio, Francesca; Lazzaroni, Elisa; Losurdo, Fabrizio; Pastore, Ida; Molteni, Laura; Berra, Cesare; Ben Nasr, Moufida; Montefusco, Laura; Bucciarelli, Loredana; Fiorina, Paolo","year":2026,"journal":"The Journal of clinical endocrinology and metabolism","doi":"10.1210/clinem/dgag072","pmid":"41729594","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15614","title":"Breaking disulfide bonds in a weakly bactericidal α-defensin unleashes a potent antimicrobial peptide with an altered conformation.","authors":"Luo, Gan; Zhao, Mingzhu; Wang, Qingxia; Zhou, Yang; Yao, Dan; Zhang, Jue; Wang, Gang; Zhang, Junjie; Liao, Chongbing; Lu, Wuyuan","year":2026,"journal":"PLoS pathogens, 22(2), e1013954","doi":"10.1371/journal.ppat.1013954","pmid":"41662431","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15615","title":"Noninvasive Biomarkers for Cardiac Allograft Rejection Monitoring: Advances, Challenges, and Future Directions.","authors":"Luo, Yijie; Lai, Junlin; Li, Chenghao; Wang, Guohua","year":2026,"journal":"Journal of clinical medicine, 15(3)","doi":"10.3390/jcm15030986","pmid":"41682667","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review categorizes rejection biomarkers by clinical utility:\n\n- Well-validated molecular tools: Donor-derived cell-free DNA (ddcfDNA) and gene expression profiling (GEP) demonstrate strong discriminative capacity for acute rejection and are commercially available\n- Emerging biomarkers: MicroRNAs (miRs) and extracellular vesicles (EVs) show considerable potential but require further validation\n- Conventional biomarkers with limitations: B-type natriuretic peptide (BNP), cardiac troponins, and creatine kinase-MB (CK-MB) offer limited specificity for rejection — they detect cardiac stress broadly but cannot distinguish rejection from other causes\n\nThe review highlights a clear shift from conventional peptide/protein biomarkers toward molecular-based approaches for post-transplant surveillance.","whyItMatters":"Heart transplant recipients currently undergo routine invasive cardiac biopsies to check for rejection — a procedure that carries risk and discomfort. Reliable blood tests could replace many of these biopsies, improving patient quality of life and reducing healthcare costs. While BNP and troponins were early candidates, this review confirms they are being superseded by more specific molecular approaches, marking a paradigm shift in transplant monitoring.","specificNumbers":"","methodology":"This is a narrative review synthesizing current evidence on blood-based biomarkers for noninvasive monitoring of cardiac allograft rejection. The authors evaluated the clinical utility, methodological challenges, and integration strategies of established and emerging biomarkers across multiple categories.","limitations":"As a narrative review, the literature search may not be comprehensive. Most biomarker studies are single-center with varying definitions of rejection and different assay methodologies, making direct comparisons difficult. The commercially available molecular tests (ddcfDNA, GEP) are expensive and not universally accessible. Long-term outcome data comparing biomarker-guided versus biopsy-guided monitoring strategies are limited. The review does not provide quantitative sensitivity/specificity comparisons across all biomarker classes."},{"rthcId":"RPEP-15616","title":"GLP-1 receptor agonists in eye disease: a comprehensive review of current research and future potential.","authors":"Luo, Yu; Xia, Yanting; Gong, Xiaohong; Hao, Meiling; Wei, Qiping; Liao, Liang","year":2026,"journal":"BMC ophthalmology, 26(1), 12","doi":"10.1186/s12886-025-04559-x","pmid":"41501669","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15617","title":"Lipid nanoparticles that co-deliver poly(I:C) and short peptide antigens elicit anti-tumor responses with vaccination.","authors":"Luo, Yuan; Li, Qinzhe; Zhou, Shiqi; Oh, Hyuna; Jablonski, James; Song, Yiting; Su, Yafei; Wu, Yun; Zhu, Haojun; Ortega, Joaquin; Lovell, Jonathan F","year":2026,"journal":"Biomaterials, 327, 123754","doi":"10.1016/j.biomaterials.2025.123754","pmid":"41075431","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15618","title":"Self-assembling freeze-dried vaccine for short HLA-A2-restricted melanoma peptide epitopes.","authors":"Luo, Yuan; Song, Yiting; Quinn, Breandan; Zhou, Shiqi; Jiao, Yang; Li, Qinzhe; Seffouh, Amal; Ortega, Joaquin; Lovell, Jonathan F","year":2026,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 114723","doi":"10.1016/j.jconrel.2026.114723","pmid":"41763270","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15619","title":"Calcitonin Gene-Related Peptide Inhibitors and Cardiovascular Events in Patients With Migraine: A Retrospective, Observational Cohort Study.","authors":"Lusk, Jay B; Wilson, Lauren E; Moore, Carlene; Yarnell, Stephanie; Kalapura, Cheryl; Choudhury, Aparna; Schrag, Matthew; Poli, Sven; Li, Fan; Mac Grory, Brian","year":2026,"journal":"Neurology, 106(3), e214479","doi":"10.1212/WNL.0000000000214479","pmid":"41499728","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15620","title":"Rare coding mutations in the glucagon-like peptide-2 pathway are associated with increased risk of binge eating disorders.","authors":"Lutter, Michael","year":2026,"journal":"Behavioural brain research, 499, 115940","doi":"10.1016/j.bbr.2025.115940","pmid":"41248737","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15621","title":"Tail clamping induces anxiety-like behaviors and visceral hypersensitivity in rat models of non-erosive reflux disease.","authors":"Lv, Mi; Liu, Xin; Huang, Kai-Yue; Wang, Yu-Xi; Wang, Zheng; Han, Li-Li; Che, Hui; Lv, Lin; Wang, Feng-Yun","year":2026,"journal":"World journal of psychiatry, 16(1), 112432","doi":"10.5498/wjp.v16.i1.112432","pmid":"41607453","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15622","title":"Tricholoma matsutake Protein as a Novel Cognitive Supportive Nutrient: Identification and Molecular Interaction Mechanism Study of Memory-Enhancing Peptides.","authors":"Lv, Renzhi; Lv, Jing; Chen, Dong; Fan, Qunyan; Lin, Songyi","year":2026,"journal":"Journal of agricultural and food chemistry, 74(8), 6878-6889","doi":"10.1021/acs.jafc.5c15371","pmid":"41705284","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15623","title":"A Simplified Three-Tailed N-Alkyl Phosphoramidate Lipid Platform Enables Inguinal Adipose-Accumulated mRNA Delivery for Anti-Obesity Therapy.","authors":"Ma, Bin; Liu, Yunxuan; Zhang, Huijuan; Fang, Yian; Xue, Yizhe; Xue, Junsheng; Jiang, Ziqiong; Zhou, Tianyan; Hao, Yanyun; Xie, Fei; Miao, Lei","year":2026,"journal":"Advanced science (Weinheim, Baden-Wurttemberg, Germany), 13(10), e17672","doi":"10.1002/advs.202517672","pmid":"41431190","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15624","title":"Multi-feature fusion for gene prediction and functional peptide identification.","authors":"Ma, Chenjing; Wei, Qianran; Wang, Guohua; Miao, Yan; Yuan, Lei","year":2026,"journal":"Frontiers in microbiology, 17, 1736391","doi":"10.3389/fmicb.2026.1736391","pmid":"41725816","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15625","title":"Dietary 18β-Glycyrrhetinic Acid Supplementation Improves Intestinal Function and Gut Microbiota in D-Galactose-Challenged Weanling Pigs.","authors":"Ma, Cui; Wang, Fuxi; Li, Ruitong; Huang, Kang; Zhao, Qingyu; Qin, Yuchang; Zhang, Junmin; Si, Wei","year":2026,"journal":"The Journal of nutrition, 156(1), 101256","doi":"10.1016/j.tjnut.2025.11.025","pmid":"41325968","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15626","title":"Gut microbiota drives the metabolic dysregulation in obesity-prone individuals by impairing GDCA-mediated activation of brown adipose thermogenesis and ileal GLP-1 secretion.","authors":"Ma, Han; Wu, Yuqi; Li, Delong; Sun, Haowen; Xie, Yuan; Zhao, Shichun; Guo, Wenqian; Wang, Meng; Cui, Renyun; Huang, Yanrong; Zhang, Xiankang; Wan, Jin-Yi; Yao, Haiqiang; Yuan, Chun-Su","year":2026,"journal":"Acta pharmaceutica Sinica. B, 16(2), 836-853","doi":"10.1016/j.apsb.2025.12.006","pmid":"41685140","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15627","title":"Anticancer selenopeptides from food sources: synthesis strategies and multitarget mechanisms.","authors":"Ma, Mingyu; Zhou, Xiaotong; Qiao, Xinyue; Li, Linling; Cheng, Shuiyuan; Lu, Yingtang; Cheng, Hua","year":2026,"journal":"iScience, 29(3), 114895","doi":"10.1016/j.isci.2026.114895","pmid":"41767278","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies selenopeptides as a new class of anticancer agents with several key features:\n\nSources and synthesis: Selenopeptides can be derived from selenium-rich foods through enzymatic hydrolysis, or synthesized via solid-phase and liquid-phase peptide synthesis\n\nMultiple anticancer mechanisms:\n- Modulation of the PI3K/Akt signaling pathway (a master regulator of cell growth and survival)\n- Activation of immune cells to attack tumors\n- Inhibition of angiogenesis (blocking new blood vessel formation that tumors need to grow)\n- Induction of cancer cell apoptosis (programmed cell death)\n\nEvidence from in vitro, in vivo, and preliminary clinical studies confirms selenopeptides can inhibit cancer cell proliferation and reduce tumor markers.","whyItMatters":"Selenium is an essential trace element with well-documented anticancer properties at appropriate doses, but selenium compounds often lack specificity and can be toxic at higher concentrations. By incorporating selenium into peptide structures, selenopeptides potentially achieve targeted delivery to tumor cells while preserving selenium's anticancer redox activity. The multitarget mechanism is particularly attractive because it makes it harder for cancer cells to develop resistance through a single mutation.","specificNumbers":"","methodology":"This is a comprehensive review article synthesizing recent literature on selenopeptide anticancer research. It covers sources, preparation methods, mechanisms of action, and evidence from preclinical and preliminary clinical studies.","limitations":"As a review, this paper does not present original data. The 'preliminary clinical studies' mentioned are not detailed in the abstract — the level of clinical evidence is unclear. Selenopeptides are a heterogeneous class with widely varying structures, and results from one selenopeptide may not apply to others. Selenium toxicity is a real concern at higher doses, and the therapeutic window for selenopeptides needs careful definition. Most evidence appears to be preclinical, and clinical translation faces significant challenges including standardization of food-derived selenopeptides."},{"rthcId":"RPEP-15628","title":"Paenitracins, a novel family of bacitracin-type nonribosomal peptide antibiotics produced by plant-associated Paenibacillus species.","authors":"Machushynets, Nataliia V; Elsayed, Somayah S; Du, Chao; Lysenko, Vladyslav; de la Cruz, Mercedes; Sanchez, Pilar; Genilloud, Olga; Martin, Nathaniel I; Liles, Mark R; van Wezel, Gilles P","year":2026,"journal":"mSystems, e0149625","doi":"10.1128/msystems.01496-25","pmid":"41700860","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The researchers identified a novel family of nonribosomal peptides designated paenitracins, representing the first bacitracin-type peptides reported in the Paenibacillus genus. Key features include:\n\n- Three previously unseen amino acid substitutions distinguish paenitracins from canonical bacitracins\n- Potent activity against gram-positive pathogens, including vancomycin-resistant Enterococcus faecium E155\n- Discovered through a novel MassQL (mass spectrometry query language)-based approach combined with molecular networking\n\nThe study also provided a comprehensive genus-wide inventory of nonribosomal peptides produced by 227 taxonomically diverse Paenibacillus strains, establishing a resource for future antibiotic discovery.","whyItMatters":"Antimicrobial resistance is one of the most urgent global health threats, with drug-resistant infections killing over 1.2 million people annually. Vancomycin-resistant Enterococcus is classified by the WHO as a high-priority pathogen for new antibiotic development. The discovery of paenitracins — natural peptide antibiotics effective against VRE — directly addresses this need. The discovery pipeline itself may be even more valuable than the specific compounds, as it provides a systematic way to find new peptide antibiotics from nature.","specificNumbers":"","methodology":"Researchers collected 227 taxonomically diverse plant-associated Paenibacillus strains and analyzed their nonribosomal peptide (NRP) production. They developed a targeted discovery pipeline using MassQL (mass spectrometry query language) combined with feature-based molecular networking to identify NRPs containing basic amino acids. Genomics-guided analysis complemented the metabolomics data. Antimicrobial activity was tested against gram-positive pathogens including drug-resistant strains. The full NRP chemical space of Paenibacillus was mapped at the genus level.","limitations":"Antimicrobial activity was demonstrated against specific lab strains; broader spectrum testing including additional resistant isolates would strengthen the case. The study focused on gram-positive activity — effectiveness against gram-negative bacteria was not reported. Drug-like properties (stability, toxicity, pharmacokinetics) of paenitracins have not been characterized. The discovery pipeline is resource-intensive and may not be accessible to all research groups. Moving from discovery to clinical development requires significant additional investment."},{"rthcId":"RPEP-15629","title":"Effects of Vairimorpha (Nosema) ceranae and Lotmaria passim on antimicrobial peptide expression in the digestive tract of honey bees (Apis mellifera L.).","authors":"MacInnis, Courtney I; Luong, Lien T; Pernal, Stephen F","year":2026,"journal":"Journal of invertebrate pathology, 214, 108435","doi":"10.1016/j.jip.2025.108435","pmid":"40885431","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15630","title":"Baseline β-Cell Secretory Reserve and Its Association with Glycaemic Control and Long-Term Outcomes Across Diabetes Phenotypes.","authors":"Maciulewski, Rafał; Buczyńska-Backiel, Angelika; Zielińska-Maciulewska, Anna; Siewko, Katarzyna; Krętowski, Adam; Szelachowska, Małgorzata","year":2026,"journal":"International journal of molecular sciences, 27(4)","doi":"10.3390/ijms27042035","pmid":"41752170","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15631","title":"Multilevel Characterization of a Chemoenzymatic Conjugated ADC by icIEF-UV/MS and RP-HPLC-MS EAD Fragmentation Peptide Map.","authors":"Mack, Scott; Liu, Haichuan; Andersson, Erica; Zhang, Yuzhuo","year":2026,"journal":"Electrophoresis, 47(2), 162-174","doi":"10.1002/elps.70069","pmid":"41527792","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The chemoenzymatic conjugation reaction produced trastuzumab-MMAE with a high yield of drug-to-antibody ratio (DAR) 2, meaning exactly two MMAE peptide payloads were attached to each antibody — a critical quality attribute for ADC efficacy and safety.\n\nMicrofluidic icIEF-UV/MS analysis separated and identified intact proteoforms of both unconjugated trastuzumab and the ADC, detecting shifts in isoelectric point and mass that confirmed successful conjugation. Trace levels of enzymatic and conjugation intermediates were also detected.\n\nRP-HPLC peptide mapping with EAD fragmentation corroborated these findings at the peptide level, localized post-translational modifications on the antibody structure, and validated that MMAE was site-specifically conjugated to the glycan structure attached at asparagine-300.","whyItMatters":"ADCs are among the fastest-growing classes of cancer drugs, but their complexity makes quality control difficult. Inconsistent drug loading can lead to toxicity (too many drug molecules) or inefficacy (too few). This workflow demonstrates that highly uniform ADCs can be produced and thoroughly characterized, which is essential for regulatory approval and patient safety. The analytical methods could become standard tools for ADC development.","specificNumbers":"","methodology":"The researchers first synthesized the ADC by conjugating the MMAE peptide payload to trastuzumab using an enzyme-mediated glycan-remodeling reaction. They then characterized the product at multiple levels: intact protein analysis using microfluidic chip-based isoelectric focusing coupled to UV detection and mass spectrometry (icIEF-UV/MS), and peptide-level analysis using reversed-phase HPLC with electron-activated dissociation (EAD) fragmentation. The two orthogonal techniques provided complementary information about conjugation efficiency, site specificity, and product homogeneity.","limitations":"This is a purely analytical and production characterization study with no biological activity or efficacy data. Only one ADC (trastuzumab-MMAE) was tested, so the workflow's applicability to other antibody-payload combinations is assumed but not demonstrated. The study does not compare this chemoenzymatic approach to other conjugation methods in terms of cost, scalability, or product quality. No in vivo or clinical data are presented."},{"rthcId":"RPEP-15632","title":"Nutritional Vulnerability in RYGB Unmasked by GLP-1 Therapy.","authors":"Madej, Juliana; Gonzaga, Ernesto Robalino; Naveed, Mariam","year":2026,"journal":"ACG case reports journal, 13(3), e02032","doi":"10.14309/crj.0000000000002032","pmid":"41767340","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A post-Roux-en-Y gastric bypass patient developed profound micronutrient deficiencies and acute liver injury after initiating semaglutide therapy, requiring ICU admission, parenteral (IV) nutrition, and endoscopic bypass reversal. The case illustrates a 'dual-hit' mechanism where GLP-1 receptor agonists compound the nutrient absorption limitations already present after bariatric surgery, creating a potentially life-threatening nutritional crisis.","whyItMatters":"With millions of people having undergone bariatric surgery and the explosive growth of GLP-1 receptor agonists like semaglutide for weight management and diabetes, the overlap between these two patient populations is rapidly growing. This case serves as a critical safety warning that combining these interventions can be dangerous, and highlights the need for careful nutritional monitoring and risk assessment before prescribing GLP-1 drugs to post-bariatric patients.","specificNumbers":"","methodology":"This is a single-patient case report documenting the clinical course, diagnostic findings, and treatment of a post-bariatric surgery patient who developed severe complications after starting semaglutide. The report describes the patient's hospitalization, laboratory findings, and the interventions required.","limitations":"As a single case report, this represents the experience of one patient and cannot establish how common this complication is. Individual factors such as dietary compliance, pre-existing nutritional status, and the specific details of the original surgery may have contributed to the severity. Case reports cannot demonstrate causation, only raise safety signals that warrant further investigation."},{"rthcId":"RPEP-15633","title":"From Venom-to-Vial-to-Pill: The Translational Journey of GLP-1 Peptides and the Evolving Landscape of Biopharmaceutics Modeling.","authors":"Madny, Muzaffaruddin Ahmed; Murthy, Aditya","year":2026,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 32(4), e70092","doi":"10.1002/psc.70092","pmid":"41734819","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15634","title":"Decoding the Heart Failure Peptidome.","authors":"Madsen, Christian T; Refsgaard, Jan C; Voordes, Geert H D; van Essen, Bart J; Ouwerkerk, Wouter; Hoegl, Annabelle; Grønborg, Mads; Tromp, Jasper; Lang, Chim C; Barascuk-Michaelsen, Natasha; Voors, Adriaan A","year":2026,"journal":"Circulation. Heart failure, e013290","doi":"10.1161/CIRCHEARTFAILURE.125.013290","pmid":"41874184","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15635","title":"Tracheocutaneous Fistula Resolved by Pentadecapeptide BPC 157 Therapy Through the NO-System-Triple NO-Agent Approach in Rats.","authors":"Madzarac, Goran; Becejac, Tomislav; Penovic, Toni; Drazenovic, Dominik; Kralj, Lucija; Popović Dolic, Marta; Sikiric, Suncana; Beketic Oreskovic, Lidija; Oreskovic, Ivana; Strbe, Sanja; Tubikanec, Ana Maria; Penavic, Mihovil; Vranes, Hrvoje; Krezic, Ivan; Kordic, Mario; Koprivanac, Antun; Vidovic, Tinka; Vlainic, Josipa; Stancic Rokotov, Dinko; Boban Blagaic, Alenka; Seiwerth, Sven; Skrtic, Anita; Sikiric, Predrag","year":2026,"journal":"Pharmaceuticals (Basel, Switzerland), 19(1)","doi":"10.3390/ph19010145","pmid":"41599743","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15636","title":"TcGAPDH peptidic inhibitors derived from dinoponeratoxin M-PONTX-Dq4e with trypanocidal effect.","authors":"Magalhães, Emanuel Paula; Lima, Dânya Bandeira; Edson, Evelline Araújo; Silva, Brenna Pinheiro; Marinho, Márcia Machado; Marinho, Emmanuel Silva; Oliveira, Vani Xavier; Pessoa Bezerra de Menezes, Ramon Róseo Paula; Martins, Alice Maria Costa","year":2026,"journal":"Toxicon : official journal of the International Society on Toxinology, 271, 108965","doi":"10.1016/j.toxicon.2025.108965","pmid":"41421647","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15637","title":"GLP- 1 Receptor Agonists in Patients with Cancer are Associated with Reduced All-Cause Mortality and Hospitalization.","authors":"Mahadevan, Aditya; Vosooghi, Aidan; Arora, Jagmeet S; Kumar, Ruthvik Sunil; Singh, Gagandeep; Tsai, Katy K; Quandt, Zoe","year":2026,"journal":"The Journal of clinical endocrinology and metabolism","doi":"10.1210/clinem/dgaf703","pmid":"41482652","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15638","title":"Molecular insights into the antimicrobial and cardiometabolic functions of Lactobacillus crispatus isolated from the reproductive tract microbiota of Indian women.","authors":"Mahajan, Shriram; Lekshmi, N; Dhiman, Proxima; Gupta, Manjari; Mudgal, Pallavi; Yadav, Rajni; Arava, Sudheer; Bhatnagar, Shinjini; Wadhwa, Nitya; Kumar, Yashwant; Talukdar, Daizee; Das, Bhabatosh; Banerjee, Sanjay K","year":2026,"journal":"Journal of biomedical science, 33(1), 7","doi":"10.1186/s12929-025-01207-w","pmid":"41486160","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15639","title":"A commercial insecticide-induced neurotoxicity and snake venom nerve growth factor-inspired peptides-mediated neuroprotection in Caenorhabditis elegans: Mechanistic, safety, and pharmacokinetic (in vivo imaging) evaluation of peptides.","authors":"Mahato, Rosy; Madhubala, Dev; Bala, Asis; Khan, Mojibur R; Mukherjee, Ashis K","year":2026,"journal":"Toxicon : official journal of the International Society on Toxinology, 275, 109038","doi":"10.1016/j.toxicon.2026.109038","pmid":"41759961","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15640","title":"Integrated proteomics, molecular dynamics, and in vitro characterization of antimicrobial peptide from Lactobacillus acidophilus vesicles against Streptococcus mutans.","authors":"Mahendrarajan, Venkatramanan; Easwaran, Nalini","year":2026,"journal":"RSC advances, 16(7), 5743-5757","doi":"10.1039/d5ra09511e","pmid":"41607481","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15641","title":"Peptide Mapping Using Multienzyme Digestion Strategies Integrated with LC-HRMS Workflow: A Case Study.","authors":"Maheshwari, Deep; Badgujar, Devendra; Kumar, Gulshan; Sharma, Nitish","year":2026,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 32(3), e70089","doi":"10.1002/psc.70089","pmid":"41699960","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15642","title":"Engineered dual-layered polyvinyl alcohol-alginate wound dressings incorporating antimicrobial and pro-healing functions.","authors":"Mahjoub, Ghazale; Zareshahrabadi, Zahra; Vaez, Ahmad; Rasaee, Mohammad Javad","year":2026,"journal":"International journal of biological macromolecules, 345, 150369","doi":"10.1016/j.ijbiomac.2026.150369","pmid":"41571126","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15643","title":"Comparative evaluation of liraglutide plus metformin combination therapy versus metformin monotherapy in patients with type 2 diabetes mellitus: A retrospective clinical study.","authors":"Mai, Tingting","year":2026,"journal":"Medicine, 105(7), e47562","doi":"10.1097/MD.0000000000047562","pmid":"41686569","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15644","title":"Comparative effectiveness of combination therapy with SGLT-2 inhibitors and GLP-1 RAs compared with SGLT-2 inhibitors in individuals with type 2 diabetes: A prevalent new-user cohort study.","authors":"Maier, Gregor A; Hennig, Beata; Rathmann, Wolfgang; Kuss, Oliver","year":2026,"journal":"Diabetes, obesity & metabolism","doi":"10.1111/dom.70523","pmid":"41725345","tags":[],"studyType":"observational","evidenceStrength":"moderate-high","keyFinding":"Combining SGLT-2 inhibitors with GLP-1 receptor agonists was associated with a 29% lower risk of death from any cause compared to SGLT-2 inhibitors alone (HR 0.71, 95% CI 0.63–0.80) in over 21,000 matched pairs of type 2 diabetes patients. The combination also showed a 19% reduction in the cardiovascular composite outcome (HR 0.81) and a 22% reduction in heart failure risk (HR 0.78). These benefits were consistent across patient subgroups and multiple sensitivity analyses.","whyItMatters":"SGLT-2 inhibitors and GLP-1 receptor agonists each have proven cardiovascular benefits individually, but real-world evidence for combining them has been limited. This large study provides strong support for the additive benefit of using both drug classes together — a strategy increasingly recommended in diabetes guidelines but not yet tested in a dedicated randomized trial.","specificNumbers":"n=21,664 matched pairs · Median follow-up 1.3 years · All-cause mortality HR 0.71 (95% CI 0.63–0.80) · CV composite HR 0.81 (0.74–0.88) · Heart failure HR 0.78 (0.68–0.89)","methodology":"Real-world cohort study using nationwide German BARMER health claims data (2013–2024). Used a prevalent new-user design matching individuals who added a GLP-1 RA to existing SGLT-2 inhibitor therapy with those continuing SGLT-2 inhibitors alone. Matching used hybrid exposure sets and time-conditional propensity scores. Cox proportional hazards models estimated hazard ratios for mortality and cardiovascular outcomes.","limitations":"Observational design means residual confounding cannot be fully excluded — patients prescribed combination therapy may be different from those on monotherapy in unmeasured ways. The median follow-up of 1.3 years is relatively short for mortality outcomes. The study uses claims data without access to lab values, imaging, or clinical notes."},{"rthcId":"RPEP-15645","title":"Advanced intranasal peptide delivery systems for improved management of Alzheimer's disease.","authors":"Majie, Ankit; Karmakar, Varnita; Ghosh, Arya; Chakraborty, Snigdha; Apurva; Layek, Buddhadev; Gorain, Bapi","year":2026,"journal":"Biomaterials advances, 178, 214474","doi":"10.1016/j.bioadv.2025.214474","pmid":"40885031","tags":["intranasal-delivery","Alzheimers-disease"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Intranasal delivery of therapeutic peptides can bypass the blood-brain barrier through nose-to-brain pathways, offering a non-invasive route to deliver Alzheimer's disease treatments directly to the brain. The review identifies key advantages: enhanced stability, rapid absorption, non-invasiveness, and improved patient compliance compared to injection-based delivery. Nanoparticle formulations can further improve the efficacy of intranasally delivered peptides by protecting them from degradation and enhancing their transport through nasal pathways.\n\nTherapeutic peptides targeting critical AD pathological processes — including amyloid aggregation, tau phosphorylation, and neuroinflammation — are promising candidates for this delivery route. However, advancing from encouraging preclinical results to clinical applications remains the central challenge.","whyItMatters":"Alzheimer's disease accounts for nearly 60% of all dementia cases, yet current treatments only manage symptoms. Many promising peptide drugs fail because they can't cross the blood-brain barrier — the brain's protective wall that blocks most drugs. Nasal delivery offers a shortcut that bypasses this barrier entirely, potentially enabling a new generation of peptide-based Alzheimer's treatments that are both effective and easy to administer.","specificNumbers":"AD = ~60% of dementia cases · nose-to-brain pathway bypasses BBB · non-invasive delivery · nanoparticle enhancement","methodology":"Review covering Alzheimer's disease mechanisms, existing therapies, brain targeting challenges, nose-to-brain delivery pathways, and recent advances in intranasal peptide delivery technologies including nanoparticle-based formulations.","limitations":"Most evidence for intranasal peptide delivery in AD comes from preclinical animal studies. Translation to humans is complicated by anatomical differences in nasal passages, the challenge of consistent dosing, and the lack of long-term safety data for chronic nasal peptide administration. The blood-brain barrier bypass through nasal delivery is well-established in animals but less proven in human clinical settings for peptide-sized molecules."},{"rthcId":"RPEP-15646","title":"Pain signaling via sensory neurons drives breast cancer progression through neuropeptide release and κ-opioid counter-regulation.","authors":"Makabe, Hitoshi; Narita, Michiko; Nagumo, Yasuyuki; Fujiwara, Masanori; Hamada, Yusuke; Takise, Jion; Yoshizawa, Takumi; Sano, Sakura; Iizuka, Shin; Asaba, Eri; Suda, Yukari; Mori, Tomohisa; Saitoh, Tsuyoshi; Nagase, Hiroshi; Tawfik, Vivianne L; Yagishita, Shigehiro; Hamada, Akinobu; Yonemori, Kan; Takayama, Shin; Yoshida, Masayuki; Yoshizawa, Ryo; Suzuki, Kenichi G N; Kasai, Rinshi S; Kuzumaki, Naoko; Satomi, Eriko; Narita, Minoru","year":2026,"journal":"Pharmacological research, 225, 108113","doi":"10.1016/j.phrs.2026.108113","pmid":"41616927","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15647","title":"Anti-CGRP monoclonal antibodies for chronic migraine with medication-overuse headache: a conservative meta-analysis.","authors":"Makita, Luana Miyahira; Carolino, Gabriela das Graças Dos Santos; Souza, Yuri Gubitose de; Brito, Heloísa Carneiro; Oliveira, Mariana; Kojima, Giovana Schlichta Adriano; Tomé, Milena Ramos; Monteiro, Júlia Dos Santos; Faller, Yasmin Bastos; Piovesan, Elcio Juliato; Peres, Mario Fernando Prieto","year":2026,"journal":"Arquivos de neuro-psiquiatria, 84(3), 1-9","doi":"10.1055/s-0046-1817018","pmid":"41760096","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15648","title":"Estimating Changes in Clinical Outcomes after Discontinuation of Anti-CGRP Targeting Therapy for Migraine Prophylaxis: A Systematic Review and Meta-analysis.","authors":"Makita, Luana Miyahira; Fagundes, Thales Pardini; Reginato, Pedro Henrique; Carpinelli, Lucca Passow; de Freitas Morais, Giovanna; Montanarin, Renata Trinkel; de Freitas Kleimmann, Rafael; Streit, Rafael Eduardo; Koppanatham, Aishwarya; Rodrigues, Andressa Christine Sales; Piovesan, Elcio Juliato","year":2026,"journal":"CNS drugs, 40(1), 71-82","doi":"10.1007/s40263-025-01233-0","pmid":"41026450","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Monthly migraine days after discontinuation were still significantly lower than pre-treatment baseline (MD -3.78 days; 95% CI: -4.89 to -2.67), indicating a lasting residual benefit even after stopping therapy.\n\nHowever, compared to the active treatment period, discontinuation led to a significant worsening: monthly migraine days increased by approximately 2.5 days and acute headache medication use rose by 3.22 days per month. The proportion of patients maintaining ≥50% reduction in migraines dropped substantially after cessation (RR 0.42; 95% CI: 0.33-0.53), meaning most patients who were responding well lost that level of benefit.","whyItMatters":"Insurance companies and clinical guidelines often require periodic treatment breaks or 'drug holidays' from anti-CGRP therapies. This meta-analysis provides the first pooled evidence of what patients can expect when treatment stops. The finding that some benefit persists beyond discontinuation is clinically important — it suggests these drugs may have partial disease-modifying effects rather than being purely symptomatic. However, the significant worsening also means discontinuation decisions should be carefully considered.","specificNumbers":"","methodology":"This systematic review and meta-analysis searched PubMed, Embase, and Cochrane databases through September 2024 for randomized or observational studies reporting outcomes after discontinuing anti-CGRP monoclonal antibodies or gepants for migraine prevention. Eight studies with 1,012 patients evaluating anti-CGRP antibody discontinuation met inclusion criteria. No gepant cessation studies were found. Random-effects models pooled mean differences and risk ratios. The study was pre-registered on PROSPERO (CRD42024595771).","limitations":"Only eight studies with 1,012 total patients were available, limiting statistical power. No studies evaluating gepant (oral CGRP pathway blocker) discontinuation were found, so conclusions apply only to injectable anti-CGRP antibodies. Heterogeneity was moderate to high for several outcomes (I² = 57-86%). Follow-up periods after discontinuation varied, making it difficult to determine how long any residual benefit lasts. The mix of randomized and observational studies introduces potential bias."},{"rthcId":"RPEP-15649","title":"Comparative Gynecological Safety of the Dual GIP/GLP-1 Receptor Agonist Tirzepatide vs. the GLP-1 Receptor Agonist Semaglutide: A Real-World Pharmacovigilance Analysis (2022-2025).","authors":"Makkena, Hima Bindu","year":2026,"journal":"Cureus, 18(1), e101738","doi":"10.7759/cureus.101738","pmid":"41704984","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15650","title":"Association of calcitonin gene-related peptide levels with cardiovascular disease in hypertensive male patients.","authors":"Makkia, Nahlah F; Khalil, Mustafa M","year":2026,"journal":"Wiadomosci lekarskie (Warsaw, Poland : 1960), 79(1), 148-155","doi":"10.36740/WLek/215250","pmid":"41759018","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15651","title":"Tirzepatide on obstructive sleep apnea-related cardiometabolic risk: secondary outcomes of the SURMOUNT-OSA randomized trial.","authors":"Malhotra, Atul; Grunstein, Ronald; Azarbarzin, Ali; Sands, Scott; Somers, Virend K; Aronne, Louis J; Jastreboff, Ania M; Lou, Jitong; Chakladar, Sujatro; Dunn, Julia P; Bunck, Mathijs C; Bednarik, Josef","year":2026,"journal":"Nature medicine, 32(2), 653-659","doi":"10.1038/s41591-025-04071-1","pmid":"41540105","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15652","title":"Severe Euglycemic Diabetic Ketoacidosis Requiring Intubation After Tirzepatide and SGLT2 Inhibitor Coadministration in a Patient With Type 1 Diabetes Mellitus From a Large Tertiary Care Centre in Karachi, Pakistan: A Case Report and Brief Review of the Literature.","authors":"Malik, Maliha; Amjad, Hammad; Malik, Khadija; Saleem, Muddassir Syed; Akhtar, Shanzay; Paracha, Muslehuddin; Abid, Mobeen; Shafi, Nabahat; Raza, Ahmed Asad; Samadi, Abedin; Jaffri, Samar Abbas","year":2026,"journal":"Clinical case reports, 14(2), e71929","doi":"10.1002/ccr3.71929","pmid":"41584389","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A 41-year-old female with type 1 diabetes developed severe euglycemic diabetic ketoacidosis (euDKA) after initiating tirzepatide for weight loss while already taking empagliflozin and basal-bolus insulin therapy. Key clinical findings:\n\n- Blood pH: 6.96 (critically low; normal is 7.35-7.45)\n- Bicarbonate: 1.5 mmol/L (critically low; normal is 22-28 mmol/L)\n- Blood glucose: only 190-200 mg/dL (mildly elevated, masking the severity)\n- Amylase: 688 U/L (elevated, suggesting possible pancreatic stress from tirzepatide)\n- No infection or other precipitating cause was identified\n\nThe severity required intubation and intravenous bicarbonate therapy. The patient recovered after intensive insulin and fluid replacement.","whyItMatters":"Tirzepatide (Mounjaro/Zepbound) is one of the most popular new medications for diabetes and weight loss, while SGLT2 inhibitors like empagliflozin are widely used for diabetes and heart failure. This case demonstrates that combining these drug classes in type 1 diabetes patients can trigger life-threatening ketoacidosis that may be missed because blood sugar levels remain deceptively normal — a critical safety consideration as off-label use of these medications expands.","specificNumbers":"","methodology":"This is a single-patient case report from a large tertiary care center in Karachi, Pakistan, with a brief review of relevant literature. The clinical course, laboratory findings, treatment, and outcome were documented prospectively during the patient's hospital admission.","limitations":"This is a single case report, which represents the lowest level of clinical evidence. It cannot establish a definitive causal relationship between the drug combination and the euDKA event. Individual patient factors may have contributed. The elevated amylase suggesting pancreatic involvement is speculative. The findings may not be generalizable to all patients combining these medications."},{"rthcId":"RPEP-15653","title":"Appetite Regulation and Allostatic Load Across Prediabetes Phenotypes.","authors":"Malin, Steven K; Heiston, Emily M","year":2026,"journal":"Nutrients, 18(1)","doi":"10.3390/nu18010158","pmid":"41515274","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15654","title":"Design of Highly Specific Antimicrobial Peptides Targeting the BamA Protein of Candidatus Liberibacter Asiaticus.","authors":"Mallawarachchi, Samavath; Irigoyen, Sonia; Mandadi, Kranthi; Borneman, James; Fernando, Sandun","year":2026,"journal":"ACS omega, 11(6), 10144-10155","doi":"10.1021/acsomega.5c11153","pmid":"41726754","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15655","title":"Characterization of the expression and function of schizophrenia risk gene Dtnbp1 in the suprachiasmatic nucleus.","authors":"Maloney, Genavieve Elizabeth; Cloutier, Marie-Ève; Provost, Micah Joseph; Srivastava, Lalit K; Cermakian, Nicolas","year":2026,"journal":"Neuroscience, 595, 250-261","doi":"10.1016/j.neuroscience.2025.12.029","pmid":"41391739","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"DTNBP1 protein was expressed throughout the SCN, with stronger expression in the dorsal region. Critically, DTNBP1 colocalized with neurons expressing both AVP (arginine vasopressin peptide) and VIP (vasoactive intestinal peptide) — two key neuropeptides that coordinate circadian rhythms across the body. Fluorescent in situ hybridization revealed time-dependent (daily rhythmic) variation of Dtnbp1 transcript expression in these neuropeptide cell bodies.\n\nHowever, in Sandy (Sdy) mice carrying a loss-of-function Dtnbp1 mutation, there was no significant effect on AVP or VIP expression in the SCN. Transmission electron microscopy showed no effect on synaptic morphology or secretory vesicles. The circadian locomotor activity disruption previously observed in these mice therefore likely involves mechanisms beyond neuropeptide expression changes or gross synaptic architecture alterations.","whyItMatters":"Circadian disruption is one of the most consistent features of schizophrenia, affecting sleep, cognition, and medication efficacy. Understanding how schizophrenia risk genes interact with the brain's clock system — and specifically with the neuropeptides that run it — could reveal new therapeutic targets. While this study found no simple disruption of VIP/AVP levels, the rhythmic expression of Dtnbp1 in these neuropeptide neurons suggests more subtle functional roles worth investigating.","specificNumbers":"","methodology":"The study used immunohistochemistry to map DTNBP1 protein expression in the SCN and determine colocalization with AVP and VIP neuropeptide neurons. Fluorescent in situ hybridization (FISH) assessed temporal expression patterns of Dtnbp1 mRNA. Sandy (Sdy) mutant mice (lacking functional DTNBP1) were compared with wild-type controls for neuropeptide expression levels and synaptic ultrastructure using transmission electron microscopy.","limitations":"The study used a single mouse model (Sandy mice) which may not fully recapitulate human schizophrenia-associated Dtnbp1 dysfunction. The null result on neuropeptide expression doesn't rule out subtler functional effects on peptide release dynamics, receptor signaling, or temporal patterning. The SCN is only one brain region where Dtnbp1 may influence circadian behavior. Sample sizes for the mouse experiments were not specified in the abstract."},{"rthcId":"RPEP-15656","title":"Mechanistic principles of antimicrobial peptides uncovered by charge density-based machine learning.","authors":"Malshikare, Hrushikesh; Priyakumar, U Deva; Chatterjee, Prathit; Sengupta, Durba","year":2026,"journal":"Chemical communications (Cambridge, England), 62(13), 4067-4070","doi":"10.1039/d5cc06374d","pmid":"41630602","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The electrostatics-stratified framework revealed three distinct antimicrobial peptide classes based on average charge per residue:\n\n1. **Low-charge/length peptides** rely on amphipathic organization through structural compactness — their killing mechanism depends on physical shape and spatial arrangement rather than electrical charge.\n\n2. **Intermediate-charge/length peptides** use a balanced combination of hydrophobicity and electrostatic attraction, employing both mechanisms in concert.\n\n3. **High-charge peptides** couple strong cationic (positive) attraction with lipophilicity and tryptophan residue anchoring to directly disrupt bacterial membranes.\n\nAcross all three classes, the hydrophobic moment — a measure of how strongly the peptide's oily and water-loving regions are separated into distinct faces — emerged as a consistently important feature for antimicrobial activity.","whyItMatters":"Antibiotic resistance is one of the greatest global health threats, and antimicrobial peptides are among the most promising alternatives. However, the diversity of AMP mechanisms has made rational design extremely difficult — what works for one type doesn't work for another. This framework provides clear, class-specific design rules: if you want a low-charge AMP, optimize compactness; for a high-charge AMP, focus on tryptophan anchoring and lipophilicity. This could dramatically accelerate the design of effective new antimicrobial peptides.","specificNumbers":"","methodology":"Researchers developed an electrostatics-stratified computational framework that grouped experimentally validated antimicrobial peptides by their average charge per residue (charge/length ratio). Each group was analyzed using integrated sequence-based, structure-based, and chemistry-based descriptors through machine learning models. The framework identified which physicochemical features are most important for antimicrobial activity within each charge class, revealing distinct molecular signatures across electrostatic regimes.","limitations":"The framework is computational and relies on existing databases of experimentally validated AMPs, which may have biases toward well-studied peptide types. The three charge-based classes may oversimplify the true diversity of AMP mechanisms — some peptides may use mechanisms not captured by sequence, structure, and chemistry descriptors alone (like immunomodulatory effects). The design guidelines haven't been prospectively validated by synthesizing and testing new peptides designed according to the proposed rules."},{"rthcId":"RPEP-15657","title":"A pitfall in diagnosing type B insulin resistance syndrome: Suspected antibody interference in a patient with insulin allergy.","authors":"Manda, Satoru; Miya, Aika; Nakamura, Akinobu; Kameda, Hiraku; Atsumi, Tatsuya","year":2026,"journal":"Journal of diabetes investigation, 17(3), 546-548","doi":"10.1111/jdi.70235","pmid":"41574820","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15658","title":"Impact of semaglutide exposure on fetal and neonatal outcomes in pregnant women: a systematic review.","authors":"Mandal, Laura; Andersen, Louise Udby; Luef, Birgitte Møller; Tanvig, Mette Honnens; Vinter, Christina Anne","year":2026,"journal":"European journal of obstetrics, gynecology, and reproductive biology, 317, 114836","doi":"10.1016/j.ejogrb.2025.114836","pmid":"41313865","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across five studies involving 1,128 semaglutide-exposed pregnancies, no clear association with birth defects was identified. One study found a spontaneous abortion rate of 23%, comparable to diabetes and obesity control groups. Another reported an 8.3% prevalence of congenital malformations but no significant risk increase compared to insulin-treated pregnancies. One study linked semaglutide discontinuation to fetal macrosomia and neonatal hypoglycemia. Overall, current evidence does not indicate a consistent increased risk of major congenital malformations from semaglutide exposure.","whyItMatters":"Millions of women of reproductive age now take semaglutide for weight loss or diabetes. Since the drug must be stopped before conception, understanding what happens when pregnancies occur during or shortly after use is critically important. This is the first systematic review to pull together all available evidence on that question.","specificNumbers":"","methodology":"The researchers conducted a systematic review, searching PubMed, Embase, and ClinicalTrials.gov for studies reporting fetal and neonatal outcomes after semaglutide exposure before or during pregnancy. Two independent reviewers screened and extracted data from the included studies. Due to high variability between studies, results were synthesized narratively rather than combined in a meta-analysis. Bias risk and study quality were formally assessed.","limitations":"Only five studies were available, involving heterogeneous designs and populations, which prevented meta-analysis. The studies varied in how they defined exposure timing, outcomes measured, and comparison groups. Risk of bias was a concern across the included research. The small total evidence base means firm conclusions cannot yet be drawn."},{"rthcId":"RPEP-15659","title":"Antioxidant, Antidiabetic, and Antimicrobial Activities of Bioactive Peptides Derived From Milk Fermented by Multi-Strain Probiotic Consortium.","authors":"Maniya, Hina; Singh, Brij Pal; Kumar, Vijay","year":2026,"journal":"Molecular nutrition & food research, 70(1), e70322","doi":"10.1002/mnfr.70322","pmid":"41277158","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Fermenting milk with a two-strain probiotic consortium (Bacillus spizizenii and Bacillus subtilis) produced bioactive peptides with markedly enhanced multi-functional activity compared to single-strain fermentation. The consortium peptides achieved 90.80% α-amylase inhibition (relevant to diabetes management), 54.17% ABTS radical scavenging (antioxidant activity), and potent antimicrobial activity with MICs of 2.5–5 µg/mL against five bacterial pathogens including Pseudomonas aeruginosa and Staphylococcus aureus.","whyItMatters":"Most research on milk-derived bioactive peptides uses single probiotic strains. This study shows that combining two indigenous probiotic strains produces peptides with stronger antidiabetic, antioxidant, and antimicrobial properties than either strain alone — suggesting that multi-strain fermentation could unlock more potent functional foods.","specificNumbers":"","methodology":"Milk was fermented using either single Bacillus strains or a two-strain consortium. Bioactive peptides (≤10 kDa) were purified from the fermented milk and characterized using reverse-phase HPLC and high-resolution LC-MS/MS. The peptides were then tested for α-amylase inhibition (a marker of antidiabetic potential), ABTS radical scavenging (antioxidant capacity), and antimicrobial activity via minimum inhibitory concentration (MIC) testing against five bacterial species.","limitations":"This was entirely an in vitro (lab-based) study — no animal or human testing was conducted. The bioactive peptides were not individually isolated and characterized, so it's unclear which specific peptides are responsible for the observed activities. Bioavailability, digestive stability, and in vivo efficacy remain unknown. The study used specific indigenous Bacillus strains that may not be commercially available."},{"rthcId":"RPEP-15660","title":"Impact of Oral Semaglutide on Kidney Outcomes in People With Type 2 Diabetes: Results From the SOUL Randomized Trial.","authors":"Mann, Johannes F E; Marx, Nikolaus; Deanfield, John E; Emerson, Scott S; Inzucchi, Silvio E; McGuire, Darren K; Mulvagh, Sharon L; Pop-Busui, Rodica; Poulter, Neil R; Engelmann, Mads D M; Hovingh, G Kees; Belmar, Nicolas; Idorn, Thomas; Jeppesen, Ole Kleist; Birkenfeld, Andreas L; Amod, Aslam; Mankovsky, Boris; Desouza, Cyrus; Gorgojo-Martinez, Juan J; Arechavaleta, Rosario; Tu, Shih-Te; Buse, John B","year":2026,"journal":"Diabetes care, 49(2), 257-265","doi":"10.2337/dc25-1080","pmid":"41380027","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15661","title":"Mechanistic Insights into Human Defensin Antimicrobial Activity from Membrane Simulations.","authors":"Manukyan, Anna K","year":2026,"journal":"The Journal of membrane biology, 259(1)","doi":"10.1007/s00232-026-00372-9","pmid":"41779197","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15662","title":"Idebenone protects against doxorubicin-induced cardiac injury by inhibiting ferroptosis in cardiomyocytes.","authors":"Mao, Jie; Zhou, Zhiyi; Xu, Yuting; Qu, Hangbo; Ma, Bo; Yu, Yihua","year":2026,"journal":"Experimental gerontology, 214, 113039","doi":"10.1016/j.exger.2026.113039","pmid":"41547496","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15663","title":"Systematic Review: Efficacy, Safety and Metabolic Outcomes of GLP-1 Receptor Agonists in Inflammatory Bowel Disease.","authors":"Maracle, Brooke; Quan, Steven; Hamilton, Patrick; Shaikh, Asma; Hazra, Deepan; Lorenzetti, Diane L; Gold, Stephanie L; Raman, Maitreyi; St-Pierre, Joëlle","year":2026,"journal":"Alimentary pharmacology & therapeutics, 63(1), 17-39","doi":"10.1111/apt.70485","pmid":"41319219","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 14 studies (13 retrospective cohort) of GLP-1 receptor agonists in adults with IBD:\n\n• 10 of 14 studies reported significant reductions in body weight, BMI, or percent weight loss\n• 4 studies demonstrated metabolic improvements: decreased HbA1c and favorable lipid changes\n• GLP-1 RA use was NOT associated with increased IBD exacerbations across multiple datasets\n• Several large registries reported REDUCED risks among GLP-1 users of: corticosteroid use, hospitalization, and surgery\n• Adverse events were primarily gastrointestinal, consistent with non-IBD populations (no excess GI toxicity from underlying IBD)\n• The findings suggest potential anti-inflammatory or disease-modifying effects, though this requires prospective confirmation","whyItMatters":"Obesity affects up to 40% of IBD patients and worsens disease outcomes, but doctors have been reluctant to prescribe GLP-1 drugs because IBD patients were systematically excluded from the clinical trials that got these drugs approved. This first systematic review provides the evidence base that gastroenterologists need to feel confident prescribing these effective weight loss medications to their IBD patients.","specificNumbers":"","methodology":"Systematic review following PRISMA guidelines (registered: PROSPERO CRD42025628850). Searched MEDLINE, Embase, Cochrane Library, and ClinicalTrials.gov through September 9, 2025. Included studies evaluating GLP-1 RAs in adults with IBD. Primary outcomes: weight-related measures. Secondary outcomes: metabolic parameters, IBD activity, and safety. Risk of bias assessed using JBI checklists. 14 studies included (13 retrospective cohort, 1 other design).","limitations":"Nearly all studies (13/14) were retrospective cohort designs, which cannot establish causation. Selection bias is a concern — healthier IBD patients may have been more likely to receive GLP-1 drugs. No randomized controlled trial data exist in IBD populations. The reduced hospitalization/surgery signals could reflect confounding rather than drug effects. Sample sizes and follow-up durations varied. Different GLP-1 drugs, doses, and IBD subtypes were pooled together."},{"rthcId":"RPEP-15664","title":"GLP-1 receptor agonists in older people with type 2 diabetes: safety evidence from the real world.","authors":"Marassi, Marella; Fadini, Gian Paolo","year":2026,"journal":"Expert opinion on drug safety, 1-5","doi":"10.1080/14740338.2026.2640982","pmid":"41773040","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15665","title":"Tirzepatide enhances liver structural integrity by promoting mitochondrial dynamics and mitophagy via PINK1/PRKN and SIRT3/NRF2 pathways in an obese-diabetic-menopausal mouse model.","authors":"Marcondes-de-Castro, Ilitch A; Marinho, Thatiany S; Aguila, Marcia B; Mandarim-de-Lacerda, Carlos A","year":2026,"journal":"Tissue & cell, 98, 103146","doi":"10.1016/j.tice.2025.103146","pmid":"40974707","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15666","title":"Tirzepatide reverses hypothalamic inflammation, cellular stress, and neuropeptide imbalance in metabolic-menopausal dysfunction.","authors":"Marinho, Thatiany Souza; Bittencourt, Julie Oliveira A; Aguila, Marcia Barbosa; Mandarim-de-Lacerda, Carlos A","year":2026,"journal":"Brain research, 1872, 150113","doi":"10.1016/j.brainres.2025.150113","pmid":"41407242","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15667","title":"Bioactive metabolite profiling in mixed-species probiotic yogurt.","authors":"Marole, Tlaleo A; Sibanda, Thulani; Buys, Elna M","year":2026,"journal":"Journal of dairy science","doi":"10.3168/jds.2025-27711","pmid":"41780866","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15668","title":"Redirecting cytomegalovirus immunity against pancreas cancer for immunotherapy.","authors":"Marrocco, Remi; Patel, Jay; Medari, Rithika; Salu, Philip; Lucero-Meza, Eduardo; Maia, Catarina; Brunel, Simon; Martsinkovskiy, Alexei; Sun, Siming; Gulay, Kevin; Jaljuli, Malak; Mose, Evangeline; Lowy, Andrew; Benedict, Chris; Hurtado de Mendoza, Tatiana","year":2026,"journal":"Journal for immunotherapy of cancer, 14(2)","doi":"10.1136/jitc-2025-012969","pmid":"41638871","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15669","title":"Trends in 1-year persistence and adherence among initiators of high-potency, weight loss-indicated glucagon-like peptide 1 receptor agonists.","authors":"Marshall, Landon Z; Gleason, Patrick P; Friedlander, Nicholas; Farley, Joel; Urick, Benjamin Y","year":2026,"journal":"Journal of managed care & specialty pharmacy, 32(3), 281-291","doi":"10.18553/jmcp.2026.32.3.281","pmid":"41760566","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15670","title":"Integrating Computational and Experimental Approaches for the Discovery of Multifunctional Peptides from the Marine Gastropod Pisania pusio with Antimicrobial and Anticancer Properties.","authors":"Martell-Huguet, Ernesto M; Moran-Avila, Thalia; Villuendas, José E; Rodriguez, Armando; Kissmann, Ann-Kathrin; Ständker, Ludger; Wiese, Sebastian; Otero-Gonzalez, Anselmo J; Rosenau, Frank","year":2026,"journal":"Marine drugs, 24(1)","doi":"10.3390/md24010032","pmid":"41590729","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15671","title":"Advances in migraine prevention.","authors":"Martinelli, Daniele; De Icco, Roberto; Al-Khazali, Haidar M; Ashina, Sait; Diener, Hans-Christoph; Dodd-Glover, Freda; Goicochea, Maria Teresa; Jenkins, Bronwyn; MaassenVanDenBrink, Antoinette; Lee, Mi Ji; Özge, Aynur; Peres, Mario Fernando Prieto; Pozo-Rosich, Patricia; Puledda, Francesca; Sacco, Simona; Schwedt, Todd; Terwindt, Gisela M; Tassorelli, Cristina","year":2026,"journal":"The Lancet. Neurology, 25(3), 279-293","doi":"10.1016/S1474-4422(25)00477-6","pmid":"41722594","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15672","title":"Characterization of Peptide-Preservative Interaction by AlphaFold, Molecular Dynamics Simulation, and NMR Spectroscopy.","authors":"Martins de Oliveira, Vinicius; Arbogast, Luke; Xie, Dan; Sharma, Pradyumn; Aboulmouna, Lina; Rose, John P; Aoto, Phillip; Hetrick, Evan M; Qian, Ken K","year":2026,"journal":"Molecular pharmaceutics, 23(2), 1128-1139","doi":"10.1021/acs.molpharmaceut.5c01527","pmid":"41429649","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15673","title":"Targeted biologics for TNBC: Advances in nanobodies, antibodies, peptides, and aptamers.","authors":"Mashayekhi, Kazem; Rahnama, Maryam; Rahman, Md Saidur; Prasad, Anisha; Islam, Shahidul M","year":2026,"journal":"Molecular therapy. Oncology, 34(1), 201138","doi":"10.1016/j.omton.2026.201138","pmid":"41716468","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15674","title":"Scorpion Venom Peptides in Ophthalmology: Insights from the Babylonian Talmud.","authors":"Maskill, David; Blizzard, Robert Morgan","year":2026,"journal":"American journal of ophthalmology, 281, 25-30","doi":"10.1016/j.ajo.2025.08.054","pmid":"40907730","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15675","title":"Sacubitril suppresses experimental chronic heart allograft vasculopathy.","authors":"Masoud, Andrew G; van Baar, Kolden; Zhu, Lin Fu; Julien, Olivier; Oudit, Gavin Y; Murray, Allan G","year":2026,"journal":"American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 26(1), 79-90","doi":"10.1016/j.ajt.2025.08.009","pmid":"40865876","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15676","title":"Distinct contributions of O-acetylserine sulfhydrylases to cysteine biosynthesis in Pseudomonas aeruginosa.","authors":"Massa, Noemi; Catalano, Flavia; Fruncillo, Silvia; Troilo, Francesca; Mellini, Marta; Favretto, Filippo; Leoni, Livia; Rampioni, Giordano; Giuffrè, Alessandro; di Matteo, Adele; Astegno, Alessandra","year":2026,"journal":"Protein science : a publication of the Protein Society, 35(3), e70498","doi":"10.1002/pro.70498","pmid":"41676964","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15677","title":"Glucagon-like peptide-1 receptor agonists in rheumatoid arthritis.","authors":"Massay, Ryan; Malani, Angela; Stubbs, Aaron","year":2026,"journal":"Current opinion in rheumatology","doi":"10.1097/BOR.0000000000001153","pmid":"41782546","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Emerging evidence suggests that GLP-1 receptor agonists may have anti-inflammatory and immunomodulatory effects relevant to rheumatoid arthritis, beyond their established roles in diabetes and obesity. However, current preclinical and clinical evidence is insufficient to recommend GLP-1 RAs as standard RA therapy. The review identifies mechanistic hypotheses for how these peptide drugs might modulate autoimmune inflammation and calls for well-designed randomized controlled trials.","whyItMatters":"Rheumatoid arthritis affects millions and requires lifelong immunosuppressive treatment. If GLP-1 drugs — already widely prescribed and well-tolerated for diabetes and obesity — prove effective against RA, it would represent a major therapeutic advance. Given that many RA patients also have metabolic comorbidities, a single drug treating both conditions would be particularly valuable. This review maps the current state of evidence for this exciting but unproven application.","specificNumbers":"Review of preclinical + clinical literature · GLP-1 RAs: established for T2DM and obesity · anti-inflammatory and immunomodulatory effects identified · insufficient evidence for RA recommendation · RCTs needed","methodology":"This is a narrative review synthesizing preclinical and clinical literature on GLP-1 receptor agonists in the context of rheumatoid arthritis. It covers mechanistic hypotheses, existing evidence, and potential clinical applications and limitations.","limitations":"The abstract acknowledges that current evidence is insufficient to support clinical use. Most evidence for anti-inflammatory effects comes from preclinical models and observational data, not RA-specific randomized trials. The specific anti-inflammatory mechanisms relevant to RA (vs general inflammation) are not fully established."},{"rthcId":"RPEP-15678","title":"Tendon, Ligament, and Muscle Injury, Osteotendinous, Myotendinous, and Muscle-to-Bone Junction Therapy Perspectives with Growth Factors and Stable Gastric Pentadecapeptide BPC 157-A Review.","authors":"Matek, Danijel; Matek, Irena; Japjec, Mladen; Matek, Mirta; Prenc, Jakov; Staresinic, Borna; Staresinic, Eva; Prtoric, Andreja; Sikiric, Suncana; Beketic Oreskovic, Lidija; Oreskovic, Ivana; Strbe, Sanja; Kordic, Mario; Tvrdeic, Ante; Seiwerth, Sven; Sikiric, Predrag; Boban Blagaic, Alenka; Skrtic, Anita; Bojanic, Ivan; Dobric, Ivan; Staresinic, Mario","year":2026,"journal":"Pharmaceuticals (Basel, Switzerland), 19(2)","doi":"10.3390/ph19020309","pmid":"41754849","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review's central finding is a clear distinction between growth factors and BPC 157 in musculoskeletal healing:\n\n**Growth factors** (PDGF, TGF-β1, IGF-1, FGF, VEGF, BMPs): When delivered locally with carriers, they improve tendon, ligament, and muscle healing individually. However, some (PDGF, TGF-β1, IGF-1) fail in muscle lesions specifically, and all show limited or no efficacy in healing the junctions — osteotendinous (tendon-to-bone), myotendinous (muscle-to-tendon), and muscle-to-bone connections.\n\n**BPC 157**: Acts alone without any carrier, combining beneficial effects on tendon, ligament, and muscle injuries simultaneously with junctional healing. In rat studies, it was effective across multiple routes — intraperitoneal injection, oral (intragastric or drinking water), and topical cream application.","whyItMatters":"Musculoskeletal junction injuries — where tendons meet bone, muscles meet tendons, or muscles attach to bone — are among the most challenging injuries in sports medicine and orthopedics. Current treatments often focus on individual tissues and neglect these critical transition zones. If BPC 157's animal study results translate to humans, it could address a major unmet need in musculoskeletal healing, particularly for complex injuries involving multiple tissue types.","specificNumbers":"","methodology":"This is a systematic review comparing the evidence for PRP, growth factors, and BPC 157 in treating musculoskeletal and junctional injuries. The authors evaluated preclinical and clinical evidence for each agent's efficacy when administered directly (locally or systemically), focusing on the ability to heal tissues and their interconnected junctions without relying on complex scaffolds or tissue engineering constructs.","limitations":"The BPC 157 evidence reviewed is overwhelmingly from rat studies, with no large-scale human clinical trials reported. Much of the BPC 157 research comes from a single research group (Sikiric et al.), raising questions about independent replication. The review's framing strongly favors BPC 157 over growth factors. Direct head-to-head comparisons between BPC 157 and growth factors in identical injury models are limited. The cytoprotection mechanism proposed is conceptual and not fully defined at the molecular level."},{"rthcId":"RPEP-15679","title":"Selective genetic targeting of the mouse efferent vestibular nucleus identifies monosynaptic inputs and indicates function as multimodal integrator.","authors":"Mathews, Miranda A; Tung, Victoria W K; Reader-Harris, Emily C; Murray, Andrew J","year":2026,"journal":"Journal of neurophysiology","doi":"10.1152/jn.00467.2025","pmid":"41770522","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15680","title":"GLP-1RA partially alleviates obesity-induced reproductive dysfunction driven by the interplay mechanisms of inflammation and metabolic dysregulation via the SIRT-associated pathway.","authors":"Matiki, Tashinga Walter; Ul Haq Shah, Mohd Zahoor; Yin, Lin; Liu, Rui; Zhu, Kejing; Lin, Zhongliang; Sheng, Jianzhong; Hefeng, Huang","year":2026,"journal":"European journal of pharmacology, 1011, 178459","doi":"10.1016/j.ejphar.2025.178459","pmid":"41380824","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Obese (HFD) female mice showed insulin resistance, elevated NF-κB-associated pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), oxidative stress, reduced SIRT1/SIRT6/FOXO3a/NRF1/eNOS, elevated FOXO1/iNOS, decreased progesterone and estradiol, elevated FSH and LH, disrupted ovarian morphology, oocyte lipid accumulation and DNA damage, and reduced fertility.\n\nSemaglutide treatment alleviated all of these dysfunctions: restoring SIRT1 and SIRT6 levels, reducing inflammation and oxidative stress, improving hormone balance, correcting ovarian structure, reducing oocyte damage, and improving fertility outcomes via modulation of the SIRT-associated pathway.","whyItMatters":"Obesity-related infertility affects millions of women worldwide and is becoming more common. This study shows semaglutide can improve fertility by directly addressing the ovarian damage caused by obesity — not just through weight loss but through specific anti-inflammatory and anti-oxidative mechanisms. This adds a fertility-related benefit to the already extensive list of semaglutide's therapeutic effects.","specificNumbers":"","methodology":"Female C57BL mice were divided into three groups: normal diet (NC), high-fat diet (HFD), and high-fat diet + semaglutide (HS). Assessments included body weight/composition, glucose/insulin/pyruvate tolerance, systemic and ovarian inflammatory cytokines, reproductive hormones, ovarian gene expression (SIRT1, SIRT6, FOXO1, FOXO3a, NRF1, IRS1, iNOS, eNOS, p27 KIP1, PTEN), ovarian histopathology, oocyte mitochondrial function, DNA damage, lipid/ROS levels, and fertility testing.","limitations":"This was a mouse study using diet-induced obesity, which may not fully replicate human obesity-related infertility. It's unclear whether semaglutide's reproductive benefits come from weight loss alone or from direct ovarian effects independent of weight. The study did not assess whether semaglutide is safe to continue during pregnancy in mice. Specific semaglutide dosing was not detailed in the abstract."},{"rthcId":"RPEP-15681","title":"Pengonadins: A penaeid shrimp-specific antimicrobial peptide family related to anti-lipopolysaccharide factors.","authors":"Matos, Gabriel Machado; Hervé, Cássio Barcellos; Argenta, Nicolas; Guzmán, Fanny; Schmitt, Paulina; Rosa, Rafael Diego","year":2026,"journal":"Fish & shellfish immunology, 168, 110978","doi":"10.1016/j.fsi.2025.110978","pmid":"41192676","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15682","title":"Integration of BNP and blood glucose for identifying coronary flow reserve impairment: A cardiovascular-kidney-metabolic perspective.","authors":"Matsumoto, Kotaro; Otsuka, Kenichiro; Kagawa, Shunsuke; Yamaura, Hiroki; Miura, Tsubasa; Sugioka, Kazuya; Saitoh, Wataru; Okamoto, Akihiro; Kajio, Go; Fujisawa, Naoki; Yamaguchi, Tomohiro; Shimada, Takenobu; Hayashi, Yusuke; Shibata, Atsushi; Ito, Asahiro; Yamazaki, Takanori; Fukuda, Daiju","year":2026,"journal":"American heart journal plus : cardiology research and practice, 61, 100671","doi":"10.1016/j.ahjo.2025.100671","pmid":"41362378","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 65 patients, 31% had impaired coronary flow reserve (CFR). BNP showed diagnostic accuracy for impaired CFR with AUC=0.74 (95% CI 0.60-0.88), while casual blood glucose had AUC=0.64 (95% CI 0.49-0.80). Combining both markers improved discrimination (p=0.03).\n\nFor structural CMD (CFR<2.0 and IMR≥25), elevated BNP (AUC=0.77, 95% CI 0.59-0.95) and higher urine albumin-to-creatinine ratio (AUC=0.71, 95% CI 0.52-0.90) were significantly associated, but casual blood glucose was not. BNP emerged as the most consistent biomarker across both functional and structural CMD definitions.","whyItMatters":"CMD is underdiagnosed because it requires invasive testing to confirm. Finding that a simple, widely available blood test — BNP — can identify patients with impaired coronary microvascular function could enable earlier detection and treatment. The CKM (cardiovascular-kidney-metabolic) framework links this to the broader understanding that metabolic disease damages small blood vessels throughout the body.","specificNumbers":"","methodology":"Retrospective analysis of 65 patients who underwent invasive coronary physiological assessment using thermodilution-derived coronary flow reserve and index of microcirculatory resistance. Clinical variables (blood glucose, BNP, urine ACR) and echocardiographic diastolic function indices were correlated with CMD measures. Diagnostic accuracy was assessed using ROC analysis.","limitations":"This is a small retrospective study of only 65 patients, limiting statistical power and generalizability. The diagnostic thresholds need validation in larger, prospective cohorts. Casual (non-fasting) blood glucose is inherently variable. The study population underwent invasive testing, so results may not represent the general population with suspected CMD."},{"rthcId":"RPEP-15683","title":"Obesity, aldosterone, and natriuretic peptides in patients with heart failure and reduced ejection fraction.","authors":"Matsumoto, Shingo; Butt, Jawad H; Docherty, Kieran F; Jhund, Pardeep S; Abraham, William T; Desai, Akshay S; Kober, Lars; Rouleau, Jean L; Packer, Milton; Vaduganathan, Muthiah; Solomon, Scott D; McMurray, John J V","year":2026,"journal":"Cardiovascular research, 122(1), 14-18","doi":"10.1093/cvr/cvaf235","pmid":"41248675","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15684","title":"Hemoglobin A1c levels in patients with type 2 diabetes mellitus receiving oral semaglutide with versus without proton pump inhibitors: An exploratory study.","authors":"Matsunuma, Satoru; Hirota, Yusuke; Yoshimoto, Koichi","year":2026,"journal":"International journal of clinical pharmacology and therapeutics","doi":"10.5414/CP204899","pmid":"41582648","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15685","title":"Changes of Intestinal Aquaporins after Experimental Polytrauma and Hemorrhagic Shock.","authors":"Mattig, Jonas Sebastian; Oezman, Deniz; Groven, Rald Victor Maria; Greven, Johannes; Zechendorf, Elisabeth; Zhao, Qun; van Griensven, Martijn; Rosado Balmayor, Elizabeth; Horst, Klemens; Sievert, Wolfgang; Halbgebauer, Rebecca; Hildebrand, Frank; Huber-Lang, Markus","year":2026,"journal":"Shock (Augusta, Ga.), 65(2), 309-315","doi":"10.1097/SHK.0000000000002682","pmid":"41615734","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15686","title":"Adverse events administering glucagon-like peptide-1 receptor agonists: a cross-sectional study.","authors":"Mattingly, T Joseph; Duru, Emeka Elvis; Conti, Rena M","year":2026,"journal":"Health affairs scholar, 4(2), qxag023","doi":"10.1093/haschl/qxag023","pmid":"41737498","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 112,532 FDA adverse event reports analyzed from 2015-2024, GLP-1 receptor agonists were associated with a much higher share of administration-related reactions (63%) compared to injectable insulin (39%). Reports of dosing issues and administration errors for GLP-1s increased starting in Q4 2022 and continued rising through 2023 and 2024 — a pattern not seen for insulin. This increase coincided temporally with national GLP-1 drug shortages that began in March 2022.","whyItMatters":"The explosive growth of GLP-1 prescribing has created a unique safety situation: a high proportion of adverse events aren't from the drug's pharmacological effects but from errors in how people use the injection devices, mix doses, or handle administration. The temporal link to drug shortages suggests that supply chain disruptions — leading to dose switching, compounded products, or unfamiliar devices — may be driving these errors. This has major implications for patient education and regulatory oversight.","specificNumbers":"","methodology":"Cross-sectional analysis of publicly available FDA Adverse Event Reporting System (FAERS) data from January 2015 through December 2024. Reports where GLP-1 receptor agonists were the primary suspect were identified and compared with reports involving injectable insulin products. Administration-related reactions, dosing issues, and temporal trends were analyzed quarterly.","limitations":"FAERS is a voluntary reporting system that lacks exposure denominators (total number of prescriptions), so increased reports may reflect increased utilization rather than increased risk. The temporal correlation with GLP-1 shortages is observational and does not prove causation. The study cannot distinguish between errors with branded products versus compounded GLP-1 preparations. Specific GLP-1 agents are not differentiated in the abstract."},{"rthcId":"RPEP-15687","title":"Injectable Peptide Therapy: A Primer for Orthopaedic and Sports Medicine Physicians.","authors":"Mayfield, Cory K; Bolia, Ioanna K; Feingold, Cailan L; Lin, Eric H; Liu, Joseph N; Rick Hatch, George F; Gamradt, Seth C; Weber, Alexander E","year":2026,"journal":"The American journal of sports medicine, 54(1), 223-229","doi":"10.1177/03635465251357593","pmid":"41476424","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15688","title":"Effects of GLP-1 Receptor Agonist Therapy on Eating Disorder Risk and Psychological Distress in Adults With Class 3 Obesity.","authors":"Maynard, Sian; Hay, Phillipa; Chimoriya, Ritesh; Acosta Reyes, Pamela; Grudzinskas, Kathy; Kormas, Nic; Piya, Milan K","year":2026,"journal":"The International journal of eating disorders, 59(2), 276-286","doi":"10.1002/eat.24575","pmid":"41139846","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15689","title":"Safety analysis of compounded GLP-1 receptor agonists: a pharmacovigilance study using the FDA adverse event reporting system.","authors":"McCall, Kenneth L; Mastro Dwyer, Keri A; Casey, Ryan T; Samana, Tasnia N; Sulicz, Ewa K; Tso, Susannah Y; Yalanzhi, Emma R; Piper, Brian J","year":2026,"journal":"Expert opinion on drug safety, 25(3), 581-588","doi":"10.1080/14740338.2025.2499670","pmid":"40285721","tags":[],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"Compounded GLP-1 receptor agonists were associated with significantly higher rates of adverse events compared to FDA-approved versions across the board. Key findings from 81,078 FAERS reports (707 compounded):\n\n- Suicidality: 6.34× higher odds with compounded products\n- Cholecystitis (gallbladder inflammation): 3.39× higher odds\n- Abdominal pain: 2.84× higher odds\n- Hospitalization: 2.35× higher odds\n- Preparation errors: 48.92× higher odds\n- Contamination: 19× higher odds\n- Compounding/manufacturing issues: 8.51× higher odds\n\nCompounded products did show lower odds of dosing errors (0.24×) and administration errors (0.29×).","whyItMatters":"Millions of people have turned to compounded semaglutide and tirzepatide due to brand-name drug shortages and high costs. This is the first large-scale pharmacovigilance analysis comparing compounded vs. FDA-approved GLP-1 drugs using FAERS data, and the results are alarming. The nearly 49-fold increase in preparation errors and 19-fold increase in contamination reports suggest serious quality control problems. The 6.34-fold increase in suicidality reports is particularly concerning and warrants urgent investigation.","specificNumbers":"81,078 total FAERS reports · 707 compounded · ROR suicidality 6.34 · ROR cholecystitis 3.39 · ROR abdominal pain 2.84 · ROR hospitalization 2.35 · ROR preparation errors 48.92 · ROR contamination 19.00 · 2018–2024 data","methodology":"Retrospective pharmacovigilance analysis of the FDA Adverse Event Reporting System (FAERS) from 2018 to 2024. Researchers compared adverse event reports for compounded versus non-compounded liraglutide, semaglutide, and tirzepatide. Reporting odds ratios (RORs) with 95% confidence intervals were calculated using logistic regression to adjust for confounders.","limitations":"FAERS is a voluntary reporting system subject to reporting bias — compounded products may attract more reports due to media attention and FDA scrutiny. The study cannot prove causation, only association. Compounded product users may differ systematically from brand-name users (e.g., no insurance, different dosing). The relatively small compounded sample (707 reports) limits the precision of some estimates. Underreporting is inherent in all voluntary adverse event databases."},{"rthcId":"RPEP-15690","title":"Rising Public Interest in Weight Loss Medications and Growing Awareness of Their Aesthetic Sequelae: An Infodemiologic Google Trends Analysis and Clinical Diagnostic Patterning.","authors":"McCarthy, Alec D; Durairaj, Kay; Linneman-Heath, Jacob; Sajic, Dusan; Dacso, Mara; Durkin, Alan","year":2026,"journal":"Journal of cosmetic dermatology, 25(1), e70670","doi":"10.1111/jocd.70670","pmid":"41521763","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15691","title":"Lower Extremity Complications in Adults With Type 2 Diabetes Treated With Glucagon-Like Peptide-1 Receptor Agonists, Sodium-Glucose Cotransporter 2 Inhibitors, Dipeptidyl Peptidase-4 Inhibitors, and Sulfonylureas: An Emulated Target Trial.","authors":"McCoy, Rozalina G; Swarna, Kavya Sindu; Polley, Eric C; Deng, Yihong; Chawla, Sagar; Neumiller, Joshua J; Galindo, Rodolfo J; Umpierrez, Guillermo E; Ross, Joseph S; Mickelson, Mindy M; Herrin, Jeph","year":2026,"journal":"Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists","doi":"10.1016/j.eprac.2026.01.012","pmid":"41638310","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15692","title":"Dulaglutide Effect on Proteins Associated With CKD Progression.","authors":"McFarlin, Brandon E; Tye, Sok Cin; Satake, Eiichiro; Md Dom, Zaipul I; Kechter, Afton; Wilson, Jonathan M; Krolewski, Andrzej S; Duffin, Kevin L","year":2026,"journal":"Kidney international reports, 11(4), 103789","doi":"10.1016/j.ekir.2026.103789","pmid":"41732754","tags":["glp-1-agonists","kidney-disease","biomarkers"],"studyType":"Post Hoc Analysis of RCT","evidenceStrength":"Moderate","keyFinding":"In patients with type 2 diabetes and moderate-to-severe chronic kidney disease (CKD), 6 months of dulaglutide treatment significantly lowered plasma levels of 14 out of 21 proteins previously linked to progression to end-stage kidney disease. The most dramatically affected were 8 TNF receptor family proteins (TNF-R1, -R2, -R3, -R4, -R6B, -R7, -R19L, -R27) — key drivers of inflammation and cell death pathways.\n\nIn contrast, these same proteins increased in patients on insulin glargine. The differences were most pronounced in patients with worse baseline kidney function, higher albumin leakage, higher HbA1c, or higher BMI — suggesting dulaglutide's kidney-protective effects may be strongest in the sickest patients. Kidney injury molecule 1 (KIM1), a marker of tubular damage, declined in both groups equally.","whyItMatters":"CKD progresses to kidney failure in millions of people, and diabetic kidney disease is the leading cause. While the AWARD-7 trial showed dulaglutide slowed kidney decline, nobody knew why at the molecular level. This study reveals that dulaglutide suppresses a broad panel of inflammatory and fibrotic proteins — particularly TNF receptors — that drive kidney damage. This provides concrete biological evidence for how GLP-1 drugs protect kidneys, beyond just improving blood sugar and weight.","specificNumbers":"n=249 (124 dulaglutide, 125 insulin glargine) · 6 months · 14 of 21 kidney proteins improved · 8 TNF receptors most affected · effects strongest in worse baseline CKD · 21-protein Joslin Kidney Panel","methodology":"Post hoc proteomic analysis of the AWARD-7 RCT. Plasma from 249 participants with T2D and CKD was analyzed using a customized OLINK proteomic platform measuring 21 proteins from the Joslin Kidney Panel (JKP), previously validated as predictors of end-stage kidney disease. Changes from baseline to 6 months were compared between dulaglutide and insulin glargine groups.","limitations":"Post hoc analysis — the trial was not designed to test proteomic endpoints. The Joslin Kidney Panel proteins are biomarkers of risk, so lowering them doesn't prove kidney damage was prevented (association vs. causation). The 6-month timeframe is relatively short for kidney disease progression. Proteomic changes may reflect systemic metabolic improvements rather than direct kidney effects. Sample size of 249 is moderate for proteomic analyses. The insulin glargine comparator doesn't represent untreated patients."},{"rthcId":"RPEP-15693","title":"Development of the European Association for the Study of Obesity (EASO) Grade-Based Framework on the Pharmacological Treatment of Obesity: Design and Methodological Aspects.","authors":"McGowan, Barbara; Ciudin, Andreea; Baker, Jennifer L; Busetto, Luca; Dicker, Dror; Frühbeck, Gema; Goossens, Gijs H; Monami, Matteo; Ragghianti, Benedetta; Sbraccia, Paolo; Martinez-Tellez, Borja; Woodward, Euan; Yumuk, Volkan","year":2026,"journal":"Obesity facts, 19(1), 84-92","doi":"10.1159/000546855","pmid":"40743997","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15694","title":"CGRP signaling links tumor-associated pain to immune evasion in oral squamous cell carcinoma.","authors":"McIlvried, Lisa A; Matos, Andre A Martel; Krane, Rachel S; Eskew, Kathryn T; LeGrande, Tian; Atherton, Megan A; Ottley, Morgan A; Nilsen, Marci L; Bell, Diana; Ahmadi, Maryam; Nikpoor, Amin Reza; Talbot, Sebastien; Scheff, Nicole N","year":2026,"journal":"Cell reports, 45(2), 116994","doi":"10.1016/j.celrep.2026.116994","pmid":"41689795","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15695","title":"Cost-effectiveness of sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists for patients with high cardiovascular risk and type 2 diabetes in Canada.","authors":"McNally, Ethan S; Marques, Pedro; Possik, Elite; Pandya, Ankur; Tsoukas, Michael A; Mavrakanas, Thomas A; Dasgupta, Kaberi; Gupta, Nisha; Sharma, Abhinav; Russell, W Alton","year":2026,"journal":"CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne, 198(7), E249-E259","doi":"10.1503/cmaj.250591","pmid":"41730540","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Compared to baseline standard-of-care treatment, both drug classes improved outcomes:\n\n- **SGLT2 inhibitors**: +0.24 QALYs, +$5,000 lifetime cost → $21,400 per QALY gained\n- **GLP-1 receptor agonists**: +0.23 QALYs, +$27,000 lifetime cost → much higher cost per QALY\n\nBoth reduced lifetime rates of cardiovascular and renal events. However, SGLT2 inhibitors were consistently cost-effective in sensitivity analyses. In 62% of probabilistic sensitivity analysis iterations, GLP-1 RA were dominated — meaning they produced fewer QALYs at a higher cost than SGLT2 inhibitors. The authors noted GLP-1 RA cost-effectiveness could improve if benefits beyond typical diabetes complications (e.g., weight loss, dementia prevention) are considered and if generic formulations become available.","whyItMatters":"Healthcare budgets are finite, and both drug classes are expensive. This study provides Canadian policymakers and clinicians with crucial evidence for deciding between GLP-1 RA and SGLT2 inhibitors as first-line add-on therapy. The finding that SGLT2 inhibitors deliver comparable health benefits at dramatically lower cost ($5,000 vs $27,000 additional lifetime cost) could influence prescribing guidelines and drug coverage decisions in Canada and similar healthcare systems.","specificNumbers":"","methodology":"Patient-level microsimulation modeling lifetime costs, clinical events, and quality-adjusted life-years (QALYs). Initial characteristics were based on 216 patients from a Quebec clinic focused on initiating guideline-directed diabetes therapies (2022-2025). Risk equations and treatment effects were calibrated to endpoints from placebo-controlled cardiovascular outcome trials. Analysis used a Canadian healthcare payer perspective, lifetime horizon, and 1.5% annual discount rate. Probabilistic sensitivity analysis assessed robustness.","limitations":"The model was based on 216 patients from a single Quebec clinic, which may not represent all Canadian diabetes patients. Treatment effects were derived from clinical trial populations that may not perfectly match real-world patients. The analysis did not include potential GLP-1 RA benefits beyond standard diabetes complications (weight loss effects, potential dementia prevention, liver disease improvement). Drug pricing is based on current Canadian costs and will change as patents expire."},{"rthcId":"RPEP-15696","title":"One-Step Design of Potent and Nonhemolytic Antimicrobial Peptides by Using a Database-Guided, Nonmachine Learning Approach.","authors":"Mechesso, Abraham F; Nair, Arjun R; Wang, Guangshun","year":2026,"journal":"ACS infectious diseases, 12(2), 805-815","doi":"10.1021/acsinfecdis.5c01022","pmid":"41558672","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15697","title":"Semaglutide Reduces Murine Blood Pressure Through the Vascular Smooth Muscle GLP-1 Receptor.","authors":"Medak, Kyle D; Koehler, Jacqueline A; Baggio, Laurie L; Gonzalez-Rellan, Maria J; Wong, Chi Kin; Cao, Xiemin; Rao, Vivikta; Kao, Sean; Cui, Yu; Fu, Jiayi; Liaw, Easton; Kabir, M Golam; Zhang, Jie; Wei, Jin; Drucker, Daniel J","year":2026,"journal":"JCI insight","doi":"10.1172/jci.insight.201148","pmid":"41774502","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 receptors in vascular smooth muscle cells (VSMCs) are essential for semaglutide to lower blood pressure in mice. When VSMC GLP-1R expression was eliminated, semaglutide could no longer reduce blood pressure, despite continuing to reduce food intake, body weight, and blood glucose normally.\n\nIn contrast, GLP-1 receptors on Tie2+ endothelial cells and immune cells were dispensable — mice lacking GLP-1R in these cell types still showed normal blood pressure reduction with semaglutide. The VSMC GLP-1R was also required for semaglutide's effects on increasing glomerular filtration rate and promoting natriuresis (sodium excretion).\n\nProteomic analysis revealed that semaglutide treatment changed protein expression in the renal artery and kidney related to platelet aggregation, fibrin clot formation, lipid metabolism, and pro-apoptotic signaling — all abolished in mice lacking VSMC GLP-1R. Additionally, semaglutide directly relaxed pre-constricted blood vessels in an ex vivo artery preparation.","whyItMatters":"GLP-1 receptor agonists like semaglutide are among the most widely prescribed drugs in the world, with expanding indications beyond diabetes into cardiovascular and kidney disease. Understanding exactly how these drugs lower blood pressure — through vascular smooth muscle, not just weight loss or endothelial effects — is critical for designing next-generation therapies and predicting which patients will benefit most from the cardiovascular and renal protective effects.","specificNumbers":"","methodology":"The researchers used genetically engineered mice with GLP-1 receptors selectively deleted from specific cell types — vascular smooth muscle cells, Tie2+ endothelial cells, or immune cells. They administered semaglutide and measured blood pressure, food intake, body weight, blood glucose, glomerular filtration rate, and natriuresis. Proteomic analysis was performed on renal artery and kidney tissue to identify molecular pathways affected by VSMC GLP-1R signaling. Ex vivo vasorelaxation experiments were conducted on pre-constricted mesenteric arteries to test direct vascular effects.","limitations":"The study was conducted in mice, and the specific cellular mechanisms may differ in humans. Blood pressure regulation in mice involves different hemodynamic parameters than in humans. The proteomic changes were observed in mouse kidney and renal artery tissue, and clinical relevance needs to be confirmed. Specific semaglutide doses and treatment durations were not detailed in the abstract."},{"rthcId":"RPEP-15698","title":"Protein disulfide isomerase dissolves and detoxifies oligomeric assemblies of amyloid beta peptide.","authors":"Mele, Antonio; Serrano, Albert; Zabala-Rodriguez, Maria C; Evangelista, Baggio A; Lehew, Haley; Kovacevic, Jasmina; Taylor, Michael; Tatulian, Suren A; Teter, Ken","year":2026,"journal":"FEBS letters","doi":"10.1002/1873-3468.70311","pmid":"41715294","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15699","title":"Primary cilia regulate GLP-1 signaling in pancreatic β cells.","authors":"Melena, Isabella; Jo, Jeong Hun; Townsend, Shannon E; DiGruccio, Samantha Adamson; Dong, Xinhang; Zhu, Lifei; Campbell, Jonathan; Hughes, Jing W","year":2026,"journal":"bioRxiv : the preprint server for biology","doi":"10.64898/2026.02.22.707280","pmid":"41757129","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15700","title":"GLP-1 and diabetic nephropathy share key molecular targets.","authors":"Melo, Wanderson Gabriel Gomes de; Dos Santos Silva, Regina Lúcia; Santos Soares, Ianahanna Duarte; de Sousa Barbosa, Bruno; Cardoso de Brito, Felipe; Argôlo Neto, Napoleão Martins; Bezerra, Dayseanny de Oliveira","year":2026,"journal":"Canadian journal of physiology and pharmacology, 104, 1-10","doi":"10.1139/cjpp-2025-0146","pmid":"41593860","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The study identified 17 shared genes between GLP-1 protein targets (from UniProt) and diabetic nephropathy-associated genes (from GeneCards), including STAT3, EP300, MAPK1, and INSR (insulin receptor). These formed a densely connected network cluster enriched in:\n\n- Insulin response pathways\n- Hypoxia adaptation\n- Apoptosis regulation\n- Glucose metabolism\n\nMolecular docking with HADDOCK demonstrated direct and favorable binding of GLP-1 to STAT3, PIK3R1, and EP300 — suggesting noncanonical mechanisms involving transcriptional regulation and epigenetic modulation that go beyond the classical GLP-1 receptor signaling pathway.","whyItMatters":"Understanding why GLP-1 drugs protect kidneys could lead to more targeted treatments for diabetic kidney disease — a condition affecting 40% of diabetic patients and a leading cause of kidney failure worldwide. The discovery of noncanonical binding targets (STAT3, EP300) suggests GLP-1 may have direct intracellular effects beyond its known receptor signaling, opening entirely new avenues for drug design and combination therapy approaches.","specificNumbers":"","methodology":"Bioinformatics approach integrating protein targets of GLP-1 from UniProt with disease-associated genes for diabetic nephropathy from GeneCards. The overlapping gene set was analyzed using STRING for protein-protein interactions and Cytoscape with MCODE for network clustering. Gene Ontology (GO) and KEGG pathway enrichment were performed using the clusterProfiler R package. Molecular docking simulations with HADDOCK validated structural interactions between GLP-1 and central network proteins.","limitations":"This is a computational/bioinformatics study without experimental validation. Molecular docking shows potential binding but doesn't prove it occurs biologically. The shared gene list depends on database completeness and may miss important targets. The 17 genes identified may not all be equally important for kidney protection. Pathway enrichment analysis reveals associations, not causation. Experimental studies (cell culture, animal models) are needed to validate these predicted interactions."},{"rthcId":"RPEP-15701","title":"Elucidating the nociceptive role of CGRP in migraine headache.","authors":"Melo-Carrillo, Agustin; Strassman, Andrew; Burstein, Rami","year":2026,"journal":"Brain : a journal of neurology","doi":"10.1093/brain/awag008","pmid":"41503630","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15702","title":"D-amino acid substitution and cyclization enhance the stability and antimicrobial activity of arginine-rich peptides.","authors":"Mendes, Bruno; Castelletto, Valeria; Hamley, Ian W; Barrett, Glyn","year":2026,"journal":"Microbiology (Reading, England), 172(2)","doi":"10.1099/mic.0.001657","pmid":"41637123","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among eight linear arginine-rich peptides tested, R4F4 showed the strongest antibacterial activity, but its effectiveness was significantly reduced in the presence of human serum and trypsin (a digestive enzyme). The D-amino acid version (D-R4F4) and cyclic version of R4F4 maintained their antimicrobial activity even in the presence of proteases.\n\nThe modified peptides worked through multiple mechanisms simultaneously: altering bacterial membrane permeability, modulating intracellular reactive oxygen species levels, and changing gene expression profiles related to metabolic pathways. They also showed substantial antibiofilm activity — both preventing biofilm formation and disrupting mature biofilms — with good cytocompatibility (safety for human cells).","whyItMatters":"Antibiotic resistance is a growing global crisis, and antimicrobial peptides represent one of the most promising alternative approaches. However, their clinical development has been stalled by poor stability in the body. This study demonstrates two practical strategies — D-amino acid substitution and cyclization — that solve the stability problem while preserving or improving antimicrobial potency, potentially unlocking peptide antibiotics for clinical use.","specificNumbers":"","methodology":"Researchers screened eight linear arginine-rich peptides computationally and experimentally for hemolytic properties (toxicity to red blood cells) and antimicrobial activity. They then designed three modified versions of R4F4 (lipidated R4F4-C16, D-amino acid D-R4F4, and cyclic R4F4) plus one R4-based variant (R4-C16). Stability was tested in the presence of human serum and trypsin. Mechanisms were investigated using fluorescence imaging, microscopy, and RNA sequencing. Biofilm assays tested both prevention and disruption of existing biofilms.","limitations":"This is entirely in vitro research with no animal or human testing. The peptides were tested against a limited set of bacterial species, and real infections involve complex environments not replicated in the lab. Manufacturing costs and scalability of cyclic and D-amino acid peptides were not addressed. Long-term resistance development against these modified peptides was not studied. The concentrations effective in vitro may differ from what is achievable in vivo."},{"rthcId":"RPEP-15703","title":"Identification and functional characterization of a Nav-targeting peptide NavTx-Bg1 from sea anemone Bunodosoma goanense (Vennam & den Hartog, 1993) transcriptome.","authors":"Menezes, Cecelia; Thakur, Narsinh; Carleer, Kathleen; Peigneur, Steve; Tytgat, Jan","year":2026,"journal":"Toxicon : official journal of the International Society on Toxinology, 273, 109016","doi":"10.1016/j.toxicon.2026.109016","pmid":"41619982","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15704","title":"Neuroprotective effects of semaglutide targeting the left temporal lobe in adults with overweight or obesity: A 24-week multimodal neuroimaging study.","authors":"Meng, Fanhua; Ao, Xiang; Lin, Xiangming; Li, Yue; Zhang, Rui; Yu, Zhiyan; Zang, Shufei; Sun, Tiange","year":2026,"journal":"Diabetes, obesity & metabolism","doi":"10.1111/dom.70524","pmid":"41657113","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15705","title":"Deoxynivalenol-induced anorexia is mediated by brain-gut peptides through CaSR-TRPM5 signaling axis.","authors":"Meng, Xiaojie; Yue, Jianming; Qin, Zihui; Xiao, Huiping; Tang, Xia; Wu, Wenda","year":2026,"journal":"Toxicon : official journal of the International Society on Toxinology, 269, 108660","doi":"10.1016/j.toxicon.2025.108660","pmid":"41241198","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15706","title":"Cm-p5, a synthetic antimicrobial peptide shows anti-Trypanosoma cruzi activity.","authors":"Mengarda, Ana C; Morales-Vicente, Fidel E; Martell-Huguet, Ernesto M; Otero-Gonzalez, Anselmo J; Silber, Ariel M","year":2026,"journal":"PLoS neglected tropical diseases, 20(3), e0013975","doi":"10.1371/journal.pntd.0013975","pmid":"41785254","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15707","title":"Prospective Comparative Analysis of Synchronous Abdominoplasty and Mastopexy in Bariatric and Nonbariatric Massive Weight Loss Patients: Highlighting the Rising Trend of GLP-1 Analog Use.","authors":"Menkü Özdemir, Fethiye Damla; Uzun, Hakan","year":2026,"journal":"Annals of plastic surgery, 96(3), 272-276","doi":"10.1097/SAP.0000000000004673","pmid":"41687026","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15708","title":"Glucagon-Like Peptide-1 Targets in the Human Nodose Ganglion.","authors":"Merchant, Warda; Mackaaij, Claire; Cleypool, Cindy G J; Gautron, Laurent","year":2026,"journal":"The Journal of comparative neurology, 534(2), e70135","doi":"10.1002/cne.70135","pmid":"41618954","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15709","title":"RYGB induces vagal sensory neuropathy characterized by altered Glp1r expression and enhanced exendin-4 responsiveness in male mice.","authors":"Merchant, Warda; Tinajero, Arely; Khan, Adan; Chu, Yi; Saleh, Sanaz; Tasabehji, Dana; Morgan, Donald A; Williams, Kevin W; Rahmouni, Kamal; Mokadem, Mohamad; Gautron, Laurent","year":2026,"journal":"American journal of physiology. Endocrinology and metabolism, 330(1), E114-E126","doi":"10.1152/ajpendo.00452.2025","pmid":"41385561","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15710","title":"Overcoming the gastrointestinal mucus barrier: Zinc-dependent modulation of mucinase activity.","authors":"Merkl, Padryk; Vukšinić, Ivana; Archer, Corey; Leroux, Jean-Christophe; Steiger, Marilena Bohley","year":2026,"journal":"International journal of pharmaceutics, 688, 126445","doi":"10.1016/j.ijpharm.2025.126445","pmid":"41325830","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15711","title":"Differential effects of the anti-obesity drug tirzepatide on adipose tissues: Brown fat as a key target.","authors":"Mestres-Arenas, Alberto; Quesada-López, Tania; Blasco-Roset, Albert; Giralt, Marta; Villarroya, Francesc; Planavila, Anna; Peyrou, Marion","year":2026,"journal":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 195, 119057","doi":"10.1016/j.biopha.2026.119057","pmid":"41592522","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15712","title":"Rare Presentation of Heterozygous PCSK1 Deficiency in an Adolescent Male.","authors":"Metzger, Tai; Jalal, Abdullah; Duran, Silvestre R","year":2026,"journal":"Case reports in pediatrics, 2026, 3460735","doi":"10.1155/crpe/3460735","pmid":"41768936","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15713","title":"Real-world 6-month persistence, adherence, and effectiveness of GLP-1 medications for overweight and obesity in a Medicaid population.","authors":"Meyer, Katelyn B; McVeigh, Mckenzie; Chiara, Ashley N; Boss, Kaelyn C; Pomfret, Thomas C; Semmel, Kyle; Bacon, Rachel; Nicolas, Diala; Clements, Karen; Alper, Caroline J; Lenz, Kimberly","year":2026,"journal":"Journal of managed care & specialty pharmacy, 32(3), 271-280","doi":"10.18553/jmcp.2026.32.3.271","pmid":"41760563","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15714","title":"Efficacy of Tongxie Yaofang compared with pinaverium bromide on irritable bowel syndrome with liver depression and spleen deficiency: a systematic review and Meta-analysis.","authors":"Mi, Zhou; Huaien, B U; Dongjun, Wang; Naijin, Zhang; Xuan, Sun; Zhikui, Tian; Hongwu, Wang","year":2026,"journal":"Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan, 46(1), 14-21","doi":"10.19852/j.cnki.jtcm.2026.01.002","pmid":"41736418","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15715","title":"Renal and metabolic effects of semaglutide plus canagliflozin vs canagliflozin alone in type 2 diabetic nephropathy.","authors":"Miao, Yan; He, Pan; Wang, Dan-Yu; Yan, Lei; Cao, Hui-Xia; Shao, Feng-Min","year":2026,"journal":"World journal of diabetes, 17(2), 112867","doi":"10.4239/wjd.v17.i2.112867","pmid":"41696107","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Adding semaglutide to canagliflozin produced superior outcomes compared to canagliflozin alone in 211 patients with diabetic nephropathy over 6 months. The combination therapy showed significantly better results across multiple measures: albumin-to-creatinine ratio (145.87 vs 158.11 mg/g, p=0.002), HbA1c (7.08% vs 7.42%, p=0.005), LDL cholesterol (86.74 vs 94.86 mg/dL, p=0.032), free fatty acids (0.46 vs 0.52 mmol/L, p=0.002), and insulin resistance index (3.94 vs 4.08, p=0.011).\n\nPancreatic β-cell function also improved with combination therapy (51.22 vs 49.36, p=0.022), and adverse event rates were comparable between groups with no increase in gastrointestinal side effects.","whyItMatters":"Diabetic nephropathy is the leading cause of end-stage kidney disease, and both semaglutide (a GLP-1 peptide drug) and canagliflozin (an SGLT2 inhibitor) are individually recommended for treatment. This study provides the first direct comparison of the combination versus monotherapy, showing the peptide drug adds meaningful kidney and metabolic benefits without extra side effects — supporting a dual-therapy approach.","specificNumbers":"n=211 (107 mono, 104 combo) · 6-month follow-up · ACR 145.87 vs 158.11 mg/g (p=0.002) · HbA1c 7.08% vs 7.42% (p=0.005) · LDL 86.74 vs 94.86 mg/dL (p=0.032) · No increase in adverse events","methodology":"Retrospective study using electronic medical records from Henan Provincial People's Hospital (October 2022 – March 2024). Patients with type 2 diabetic nephropathy were divided into canagliflozin monotherapy (n=107) or canagliflozin plus semaglutide combination (n=104). Renal function, glucose metabolism, lipid profiles, pancreatic function, oxidative stress, and inflammatory markers were assessed at baseline and 6 months. Adverse events were monitored throughout.","limitations":"This is a retrospective, non-randomized study from a single hospital, introducing potential selection bias — patients prescribed the combination may differ systematically from monotherapy patients. The 6-month follow-up is relatively short for kidney outcomes. Long-term kidney function preservation (eGFR decline, progression to dialysis) was not assessed. The study lacks randomization and blinding, limiting causal conclusions."},{"rthcId":"RPEP-15716","title":"GLP-1 Receptor Agonists as Treatment of Nondiabetic Ischemic Stroke: A Systematic Review and Meta-Analysis.","authors":"Michaelsen, Michael Knudsen; Drasbek, Kim Ryun; Valentin, Jan Brink; Svart, Mads; Larsen, Julie Brogaard; Kruuse, Christina; Simonsen, Claus Ziegler; Blauenfeldt, Rolf Ankerlund","year":2026,"journal":"Stroke, 57(2), 415-437","doi":"10.1161/STROKEAHA.125.053075","pmid":"41263069","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15717","title":"LEAP2 acts in hepatocytes and at central level, alleviates steatosis and inflammation but resistance in obese and aging.","authors":"Miguéns, Marta V; Quintela-Vilariño, Carmen; Casado, Sabela; de Oliveira-Diz, Tadeu; Müller, Timo D; Nogueiras, Rubén; Diéguez, Carlos; Tovar, Sulay","year":2026,"journal":"Life sciences, 388, 124219","doi":"10.1016/j.lfs.2026.124219","pmid":"41571146","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"LEAP2 demonstrated dose-dependent effects across different experimental models:\n\n• In human and mouse hepatocyte cultures: LEAP2 inhibited lipid accumulation, confirming a direct effect on liver cell fat metabolism.\n• In mice on standard diet: Central (brain) administration of LEAP2 reduced hepatic lipid deposition.\n• In young mice on high-fat diet: LEAP2 did not prevent diet-induced steatosis but did attenuate hepatic inflammation.\n• In aged mice: LEAP2 failed to suppress both age-associated inflammation and steatosis.\n\nThe progressive loss of LEAP2 effectiveness from normal conditions to high-fat diet to aging suggests a resistance phenomenon, similar to insulin or leptin resistance seen in obesity and metabolic syndrome.","whyItMatters":"Fatty liver disease (MAFLD) is the world's most common liver disorder with no approved drug to reverse it. The discovery that LEAP2 — your body's own ghrelin-blocking peptide — can reduce liver fat and inflammation opens a new therapeutic angle. However, the finding that LEAP2 loses effectiveness in obesity and aging (the very conditions that cause MAFLD) reveals a critical challenge that must be overcome for this pathway to become clinically useful.","specificNumbers":"","methodology":"The study combined in vitro and in vivo approaches. In vitro experiments used human and mouse hepatocyte cultures to test LEAP2's direct effects on lipid metabolism. In vivo studies used chronic central (intracerebroventricular) LEAP2 administration in mouse models of diet-induced steatosis (high-fat diet in young mice) and age-related steatosis (aged mice). Outcomes included hepatic lipid content, inflammation markers, and metabolic parameters.","limitations":"LEAP2 was administered centrally (into the brain ventricles) rather than peripherally, which may not reflect how a therapeutic peptide would be delivered clinically. The study used mouse models that may not fully replicate human MAFLD. The failure in both high-fat diet and aging models is concerning for translational potential. Specific dosing details and duration of treatment are not provided in the abstract. No human clinical data exist."},{"rthcId":"RPEP-15718","title":"Oligopeptides as molecular carriers in antimicrobial conjugates.","authors":"Milewski, Sławomir; Wichrowska, Wiktoria; Milewska, Maria J","year":2026,"journal":"Expert opinion on drug delivery, 23(2), 221-245","doi":"10.1080/17425247.2025.2581841","pmid":"41139849","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15719","title":"National Poison Center Trends in GLP-1 Receptor Agonist Exposures Following FDA Approval for Weight Loss.","authors":"Miller, Jordan; Miller, Robert; Varney, Shawn M; Han, David","year":2026,"journal":"Journal of medical toxicology : official journal of the American College of Medical Toxicology","doi":"10.1007/s13181-026-01121-z","pmid":"41634285","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Over 10,033 GLP-1 receptor agonist exposures were reported to U.S. poison centers from 2012 to 2023. After semaglutide's weight loss approval in July 2021, case volumes more than doubled (3,113 pre-approval vs. 6,920 post-approval). Semaglutide became the dominant agent, accounting for 64.2% of post-approval reports.\n\nThe exposed population shifted younger and more female, consistent with the drug's new weight loss demographic. Most cases involved unintentional therapeutic errors with mild gastrointestinal symptoms. However, the proportion of cases requiring healthcare facility involvement increased significantly from 23.0% to 33.5% (RR = 1.46, p < 0.001). Segmented Poisson regression showed semaglutide exposures increased an additional 9.9% per quarter after approval.","whyItMatters":"Millions of people worldwide are now taking GLP-1 drugs for weight loss, and the rapid adoption has outpaced safety education. This study provides the first national-level picture of how that expansion has translated into real-world safety events. While most incidents are mild, the increase in healthcare visits suggests many people are confused about dosing or side effects — a problem that better patient counseling could address.","specificNumbers":"","methodology":"The researchers analyzed all human GLP-1 receptor agonist exposures reported to the National Poison Data System (NPDS) from 2012 to 2023. They used July 1, 2021 (semaglutide's weight loss approval date) to divide data into pre- and post-approval periods. Demographics, exposure characteristics, treatments, and outcomes were compared using standardized statistical tests. Quarterly call volumes were modeled using segmented Poisson regression to quantify changes in reporting trends.","limitations":"Poison center data captures only voluntarily reported cases, likely underestimating the true number of exposures. The study cannot distinguish whether increased reporting reflects more actual incidents or greater awareness of poison centers. The data does not include cases managed entirely by healthcare providers without poison center involvement. The observational design cannot establish causation between the FDA approval and increased exposures — other factors like media coverage and off-label use may have contributed."},{"rthcId":"RPEP-15720","title":"Incidence of dementia in patients with type 2 diabetes using SGLT2 inhibitors versus GLP-1 receptor agonists or DPP-4 inhibitors: A systematic review and meta-analysis of cohort studies.","authors":"Milori, Pedro Henrique; Armelin, Larissa Maria; Mutarelli, Antônio; Caramelli, Paulo","year":2026,"journal":"Journal of Alzheimer's disease : JAD, 109(2), 594-603","doi":"10.1177/13872877251395086","pmid":"41252314","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15721","title":"Real-world effectiveness and safety of tirzepatide in Japanese patients with type 2 diabetes: A multi-site retrospective study.","authors":"Minakata, Yusuke; Miura, Masaki; Nakatake, Nobuhiro; Masuzawa, Masahiro","year":2026,"journal":"Diabetes, obesity & metabolism","doi":"10.1111/dom.70550","pmid":"41674229","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15722","title":"Topiramate Enhances GABAergic Tone to Orexigenic Neuropeptide Y/Agouti-Related Peptide (NPY/AgRP) Neurons.","authors":"Minbashi Moeini, Moein; Lavoie, Olivier; Caron, Alexandre; Williams, Kevin W; Michael, Natalie J","year":2026,"journal":"Obesity (Silver Spring, Md.), 34(1), 175-187","doi":"10.1002/oby.70051","pmid":"41039657","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"At a concentration of 1 μM, topiramate strongly inhibited the electrical activity of orexigenic NPY/AgRP neurons in the arcuate nucleus of the hypothalamus. This is the first study to demonstrate this effect.\n\nThe mechanism was unexpected: despite topiramate's well-established actions at GABAA receptors, the inhibition of NPY/AgRP neurons did not involve GABAA receptors. Instead, the effect required synaptic transmission and was blocked by GABAB receptor antagonists and potassium channel blockers, suggesting topiramate enhances GABAergic inhibitory tone through a GABAB-mediated pathway. Notably, topiramate had negligible effects on anorexigenic POMC neurons, demonstrating selectivity for the hunger-promoting neural population.","whyItMatters":"Topiramate is already used for weight management (alone off-label or combined with phentermine as Qsymia), but its mechanism was poorly understood. Identifying that it selectively silences hunger-promoting NPY/AgRP neuropeptide neurons through GABAB signaling provides a clear mechanistic target that could guide the development of more precise anti-obesity drugs with fewer side effects.","specificNumbers":"","methodology":"Researchers used transgenic mice with fluorescently labeled NPY/AgRP or POMC neurons to perform whole-cell patch clamp electrophysiology in brain slices of the hypothalamic arcuate nucleus. This technique measures the electrical activity of individual neurons in real time. They applied topiramate and systematically tested pharmacological blockers to dissect the signaling pathway — blocking synaptic transmission, GABAA receptors, GABAB receptors, and potassium channels to determine which components were necessary for topiramate's inhibitory effect.","limitations":"This is an in vitro electrophysiology study in mouse brain slices, not a whole-animal or human study. The topiramate concentration used (1 μM) may not directly correspond to brain tissue levels achieved with typical oral dosing. Transgenic mouse models may not perfectly replicate human hypothalamic circuitry. The study demonstrates an acute effect on neuronal activity but does not show long-term changes in feeding behavior or body weight."},{"rthcId":"RPEP-15723","title":"Rewriting Diabetes Therapy: How Incretin Modulation is Transforming Cardiovascular and Renal Outcomes.","authors":"Miramontes-González, José Pablo; Rodrigo-Alaíz, Álvaro; Gabella-Martín, Miriam; González-Calle, David; Carretero-Gómez, Juana; Corral-Gudino, Luis","year":2026,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders","doi":"10.1007/s13300-025-01829-1","pmid":"41489681","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15724","title":"A multipronged Tα1 reset of CD8+ T cell cytotoxicity against breast cancer.","authors":"Mishra, Smriti; Telang, Gaurang; Sureshbabu, Anurag; Kulkarni, Samruddhi; Thayagrajan, Senthil; Kumar, A W Santhosh; Singh, Rajshri","year":2026,"journal":"Human immunology, 87(3), 111678","doi":"10.1016/j.humimm.2026.111678","pmid":"41619634","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tα1 significantly enhanced CD8+ T cell-mediated apoptosis of MDA-MB-231 breast cancer cells and CD44+ cancer stem-like cells, suppressed tumor cell proliferation, and increased granzyme B secretion beyond what standard CD3/CD28 stimulation alone achieved.\n\nIn exhausted T cells, Tα1 partially restored effector function and reduced expression of three key immune checkpoint receptors: PD-1, TIM-3, and LAG-3. A complementary transcriptomic analysis using a four-gene Tα1 Response Index (TLR9, TLR2, IRF1, NLRC5) applied to 1,112 breast cancer patients from TCGA confirmed positive correlations with antigen presentation and cytotoxic programs, with enrichment in CD8-like T cells in single-cell datasets.","whyItMatters":"T cell exhaustion is a major obstacle in cancer immunotherapy — even powerful treatments like checkpoint inhibitors struggle when T cells are too depleted to fight. Tα1 offers a peptide-based approach to reinvigorate exhausted T cells while also directly boosting their cancer-killing capacity. Unlike many immunotherapies, Tα1 is already approved in several countries for hepatitis and immune support, which could facilitate clinical translation for cancer applications. Its ability to target cancer stem-like cells (CD44+) is particularly notable, as these cells drive tumor recurrence.","specificNumbers":"","methodology":"CD8+ T cells were isolated from peripheral blood of 10 healthy donors and cultured under four conditions: unstimulated, CD3/CD28-stimulated, Tα1-treated, or exhaustion-rescue. Cytotoxic activity was evaluated against MDA-MB-231 triple-negative breast cancer cells and CD44+ cancer stem-like cells. Granzyme B secretion was measured, and exhaustion markers (PD-1, TIM-3, LAG-3) were assessed. A four-gene Tα1 Response Index was validated against TCGA-BRCA transcriptomic data (n=1,112) and single-cell RNA sequencing datasets.","limitations":"This is primarily an in vitro study using T cells from healthy donors, not cancer patients whose T cells may behave differently. The MDA-MB-231 cell line represents triple-negative breast cancer and may not reflect other breast cancer subtypes. The TCGA validation is correlative — it shows associations between Tα1-responsive genes and immune programs but doesn't prove Tα1 would work in vivo. No animal tumor models or clinical data were presented. The sample size of 10 donors is modest for functional immunology experiments."},{"rthcId":"RPEP-15725","title":"Markov State Models Reveal How hLL-3717-29 Tetramers Relax from a Disordered State to a Cross-α Amyloid Geometry.","authors":"Mitra, Aritra; Paul, Sandip","year":2026,"journal":"The journal of physical chemistry. B, 130(8), 2377-2387","doi":"10.1021/acs.jpcb.5c07747","pmid":"41665928","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15726","title":"GLP-1 receptor agonist therapy is not associated with adverse events following shoulder surgery: a systematic review and meta-analysis.","authors":"Moews, Logan D; Kunze, Kyle N; Thamrongskulsiri, Napatpong; Vega, Tomas F; Morgan, Jacob T; Nishioka, Tanner; Chahla, Jorge; Verma, Nikhil N","year":2026,"journal":"Journal of shoulder and elbow surgery","doi":"10.1016/j.jse.2025.12.005","pmid":"41619919","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"For total shoulder arthroplasty (TSA), the pooled 90-day complication rate was 18.1% for GLP-1 users versus 15.9% for non-users, with no statistically significant difference (OR = 0.86, 95% CI: 0.36–2.07, P = 0.74). At 2 years, rates were nearly identical: 3.8% vs 3.7% (OR = 1.24, 95% CI: 0.73–2.00, P = 0.42).\n\nFor arthroscopic procedures, GLP-1 users showed notably lower 90-day complication rates. After rotator cuff repair, complications were 11.0% vs 27.4% in non-users. After capsular release for adhesive capsulitis, rates were 2.5% vs 4.8%. Re-tear rates after rotator cuff repair were also lower in GLP-1 users at 2 years (12.5% vs 18.3%), though these arthroscopic findings were from limited studies described narratively rather than pooled.","whyItMatters":"With GLP-1 drugs becoming some of the most prescribed medications in the world, millions of users will need surgery at some point. Surgeons and patients need reliable data on whether these drugs affect surgical outcomes. This study provides reassurance that GLP-1 use does not increase shoulder surgery complications, which is particularly important given concerns about wound healing and tissue quality in patients taking weight-loss medications.","specificNumbers":"","methodology":"The researchers conducted a PRISMA-compliant systematic review and meta-analysis, searching PubMed, Embase, and Scopus through August 2025. They included Level I–III comparative studies that assessed postoperative adverse events in GLP-1 users vs non-users after total shoulder arthroplasty or arthroscopic shoulder procedures. Random-effects meta-analyses were performed for the four TSA studies, while the two arthroscopic studies were described narratively due to limited data. Outcomes included 90-day and 2-year complication rates.","limitations":"Only six studies met inclusion criteria, and the arthroscopic findings couldn't be meta-analyzed due to limited data. The studies were observational, not randomized controlled trials, so confounding factors may influence results. GLP-1 users likely differed from non-users in baseline characteristics beyond the adjustments made. The study couldn't determine specific GLP-1 drugs, doses, or duration of use. Publication bias is possible given the topic's novelty."},{"rthcId":"RPEP-15727","title":"GLP-1 receptor agonist initiation and risk of colorectal cancer and colonic polyps.","authors":"Moh'd Mari, Anwar Alshaakh; Alamin, Faris; Le, Minh Anh; Rizvi, Ali; Mansi, Ishak A","year":2026,"journal":"The American journal of the medical sciences","doi":"10.1016/j.amjms.2026.02.002","pmid":"41698506","tags":["glp-1"],"studyType":"cohort","evidenceStrength":"strong","keyFinding":"In a propensity-score-matched study of 86,083 pairs of diabetes patients, GLP-1 receptor agonist users had no increased or decreased risk of colorectal cancer compared to DPP-4 inhibitor users (OR=0.99, 95% CI: 0.84–1.17). However, GLP-1RA users had a modestly higher incidence of colonic polyps (5.9% vs. 5.3%; OR=1.12, 95% CI: 1.08–1.17).\n\nThe polyp finding persisted even when patients with pre-existing polyps were excluded from the analysis, strengthening the signal. However, the absolute difference was small (0.6 percentage points), and colonic polyps are very common and usually benign.","whyItMatters":"With millions of people now taking GLP-1 drugs, understanding their long-term cancer risk is critical. Some earlier research suggested GLP-1 drugs might protect against colorectal cancer, while other studies raised concerns about tumor promotion. This large, well-designed study settles part of the debate — no cancer link — but raises a new question about colonic polyps that warrants monitoring.","specificNumbers":"86,083 matched pairs · GLP-1RA vs DPP-4i · CRC: OR=0.99 (no difference) · Polyps: 5.9% vs 5.3% · OR=1.12 for polyps · 61 PS-matching variables · 2006–2021","methodology":"Retrospective propensity-score-matched cohort study using a new-user, active comparator design (GLP-1RA vs DPP-4 inhibitors). Researchers matched 86,083 pairs using 61 variables to eliminate confounders. A secondary analysis excluded patients with baseline polyps. Data covered 2006–2021. Primary outcomes were incident colorectal cancer and colonic polyps.","limitations":"Retrospective observational design cannot prove causation. The higher polyp detection in GLP-1RA users could reflect detection bias — if GLP-1RA users had more colonoscopies (perhaps related to GI symptoms from the drug), more polyps would be found. The study compared GLP-1RA to DPP-4i, not to placebo or non-diabetic patients, so findings are relative to another active drug. Follow-up may be too short to capture slower-developing cancers."},{"rthcId":"RPEP-15728","title":"Selective cytotoxicity of microcin H47 against MDA-MB-231 breast cancer cells: an antimicrobial peptide with therapeutic potential.","authors":"Mohammadzadeh Rostami, Farzaneh; Shalibeik, Saman","year":2026,"journal":"Archives of microbiology, 208(4), 192","doi":"10.1007/s00203-026-04731-x","pmid":"41677815","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15729","title":"Variable Effects of Glucagon Like Peptide-1 Receptor Agonists on Body Composition in Older Women.","authors":"Mohammed, Arshad; Mishra, Sneha","year":2026,"journal":"AACE endocrinology and diabetes, 13(1), 63-66","doi":"10.1016/j.aed.2025.09.012","pmid":"41641313","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15730","title":"Fish-Derived Antimicrobial Peptides (AMPs) as Anticancer Agents: A Mini-Review of In Vitro Evidence.","authors":"Mohd Noordin, Muhammad Akram; Najm, Ahmed Abdulkareem; Dyari, Herryawan Ryadi Eziwar; Law, Douglas; Fazry, Shazrul","year":2026,"journal":"Anti-cancer agents in medicinal chemistry","doi":"10.2174/0118715206411478251125091213","pmid":"41787994","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 15 studies published between 2020 and 2024, fish-derived antimicrobial peptides (AMPs) demonstrated broad-spectrum anticancer activity against diverse cancer cell lines. The primary killing mechanisms were apoptosis and necrosis triggered through reactive oxygen species (ROS) generation, mitochondrial dysfunction, and DNA damage. Notably, these peptides showed selective cytotoxicity — preferentially killing cancer cells while being less toxic to normal cells. Some also exhibited antiangiogenic properties (blocking tumor blood vessel formation).","whyItMatters":"Cancer treatment needs new drug classes, especially those that can selectively target tumor cells. Fish-derived AMPs offer a promising direction because they kill cancer cells through multiple mechanisms simultaneously, making resistance harder to develop. Their selectivity for cancer cells over normal cells is particularly appealing, as conventional chemotherapy's lack of selectivity causes severe side effects.","specificNumbers":"15 studies reviewed (2020–2024) · Multiple cancer cell lines tested · Mechanisms: ROS generation + mitochondrial dysfunction + DNA damage · Selective cytotoxicity demonstrated","methodology":"Systematic mini-review of studies published between 2020 and 2024, sourced from Google Scholar, Scopus, BioMed Central, and ScienceDirect. Fifteen relevant research papers were identified and analyzed for evidence of fish-derived AMP anticancer activity, mechanisms of action, and therapeutic potential.","limitations":"All evidence reviewed is from in vitro (cell culture) studies only — no animal models or human clinical trials are included. In vitro anticancer activity often fails to translate to in vivo efficacy due to peptide instability, poor bioavailability, and immune clearance. The review only covered 15 papers from a 4-year window, which may not capture the full scope of the field."},{"rthcId":"RPEP-15731","title":"Management of Peptide Receptor Radionuclide Therapy Toxicities in Neuroendocrine Neoplasm Patients.","authors":"Mohindroo, Chirayu; Ramirez, Robert A","year":2026,"journal":"Current treatment options in oncology, 27(1), 6","doi":"10.1007/s11864-026-01379-z","pmid":"41543636","tags":[],"studyType":"review","evidenceStrength":"moderate","keyFinding":"This review provides a comprehensive guide to managing the toxicities of peptide receptor radionuclide therapy (PRRT) with lutetium-177 DOTATATE in neuroendocrine tumor patients. Toxicities can be acute, subacute, or long-term, affecting multiple organ systems. Key management topics include screening for clonal hematopoiesis before treatment (a risk factor for blood cancers), steroid prophylaxis to prevent carcinoid crisis and bowel obstruction, and evidence-based monitoring strategies for kidney and bone marrow toxicity.","whyItMatters":"As PRRT use grows with rising neuroendocrine tumor incidence, more clinicians need practical guidance on managing its side effects. This review consolidates current evidence on toxicity management into a single resource, addressing emerging concerns like pre-treatment clonal hematopoiesis screening that could prevent rare but serious blood cancers.","specificNumbers":"Key trials referenced: NETTER-1 and NETTER-2 · Agent: lutetium-177 DOTATATE · Toxicity timeframes: acute, subacute, long-term","methodology":"Narrative review of published literature on PRRT toxicities, summarizing evidence from clinical trials (NETTER-1, NETTER-2) and clinical experience with monitoring, prevention, and management strategies.","limitations":"Narrative review without systematic search methodology or meta-analysis. Management recommendations are based on available evidence and clinical experience, which may be limited for rare toxicities. The rapidly evolving nature of PRRT practice means some recommendations may change quickly."},{"rthcId":"RPEP-15732","title":"Topic and Sentiment Trends in Semaglutide Discussions on X: Subpopulation-Based Longitudinal Analysis.","authors":"Momeni, Parisa; Laverghetta, Gabriel; Ligatti, Jay; Li, Lingyao","year":2026,"journal":"Online journal of public health informatics, 18, e80660","doi":"10.2196/80660","pmid":"41734897","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15733","title":"Unveiling antihypertensive and antimicrobial peptides from wine lees: Enzymatic hydrolysis, peptidomics profiling, virtual screening, functional characterization, and molecular docking.","authors":"Monasterio, Romina; Iram, Daraksha; Knuf, Franziska; Caspers-Weiffenbach, Rita; Fontana, Ariel","year":2026,"journal":"Food research international (Ottawa, Ont.), 229, 118462","doi":"10.1016/j.foodres.2026.118462","pmid":"41763785","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Enzymatic hydrolysis of wine lees proteins with alcalase, flavourzyme, and protease produced peptides with both ACE inhibitory and antimicrobial activities. Protease hydrolysate showed the highest antimicrobial activity against E. coli, associated with a high proportion of positively charged peptides.\n\nIn silico gastrointestinal digestion simulation identified 34 ACE-inhibitory peptide sequences from the hydrolysates. Of these, 8 di-/tripeptides (AF, AW, GF, GL, GW, PL, PM, VW) were predicted to have positive human intestinal absorption. VW and AW showed the strongest ACE binding energies (lower than -8.0 kcal/mol) in molecular docking. All predicted peptides were non-toxic with desirable drug-like properties per Lipinski's rule-of-five.","whyItMatters":"The wine industry generates massive amounts of lees waste. Converting this into bioactive peptide ingredients serves dual purposes: reducing environmental waste and creating value-added health products. The simultaneous identification of blood-pressure-lowering and antimicrobial peptides from a single waste source is particularly appealing for the functional food industry, where multifunctional ingredients command premium prices.","specificNumbers":"","methodology":"Wine lees proteins were hydrolyzed with three proteases individually and in combination. Peptidomics profiling used nano-LC-Orbitrap tandem mass spectrometry. Virtual screening categorized peptides by bioactivity. In silico gastrointestinal digestion simulated peptide release. ADMET (absorption, distribution, metabolism, excretion, toxicity) properties were predicted using physicochemical modeling. Molecular docking characterized ACE binding interactions. Antimicrobial activity was tested against food-borne organisms.","limitations":"All ACE inhibitory and bioavailability data are based on in silico predictions and molecular docking — no actual in vitro ACE inhibition assays or in vivo blood pressure studies were reported. Computational predictions of bioavailability often differ from experimental results. The antimicrobial activity was demonstrated in vitro but not in food preservation contexts. Predicted gastrointestinal stability of these small peptides needs experimental validation. Scale-up economics and regulatory pathways for food ingredient applications were not addressed."},{"rthcId":"RPEP-15734","title":"Implementation of guideline-directed medical therapy in patients with heart failure and obesity: European Journal of Heart Failure expert consensus document.","authors":"Monzo, Luca; Savarese, Gianluigi; Mullens, Wilfried; Abdelhamid, Magdy; Antohi, Elena-Laura; Jhund, Pardeep S; Iacoviello, Massimo; Lee, Matthew M Y; Lindberg, Felix; Platz, Elke; Metra, Marco; Girerd, Nicolas","year":2026,"journal":"European journal of heart failure","doi":"10.1093/ejhf/xuag027","pmid":"41771102","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15735","title":"Semaglutide vs tirzepatide in patients with obesity and HFpEF: a report from a global federated research network.","authors":"Monzo, Luca; Savarese, Gianluigi; Duarte, Kevin; Baudry, Guillaume; Petrie, Mark C; Girerd, Nicolas","year":2026,"journal":"ESC heart failure, 13(1)","doi":"10.1093/eschf/xvag042","pmid":"41711744","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"After propensity score matching in 2,516 patients (1,258 per group), semaglutide and tirzepatide showed no significant difference in the composite of all-cause mortality and heart failure hospitalization over a median 24-week follow-up (HR 1.14, 95% CI 0.89–1.46, p=0.286). Individual components were also similar: all-cause death HR 1.24 (p=0.531) and HF hospitalization HR 1.10 (p=0.471). Results were consistent regardless of diabetes status.","whyItMatters":"While tirzepatide produces greater weight loss than semaglutide in general obesity populations, clinicians and patients with HFpEF need to know whether that translates into better heart outcomes. This large real-world comparison provides the first direct evidence that both drugs perform similarly for the outcomes that matter most — death and hospitalization — giving clinicians confidence that either option is reasonable for obese HFpEF patients.","specificNumbers":"","methodology":"Non-randomized, observational cohort study using electronic health records from the TriNetX Global Collaborative Research Network. Adults with obesity and HFpEF who started semaglutide or tirzepatide for the first time between November 2023 and May 2025 were identified. Propensity score matching was used to balance the groups (1,258 per arm). The primary endpoint was a composite of all-cause mortality and HF hospitalization.","limitations":"This is an observational study, not a randomized trial, so residual confounding is possible despite propensity score matching. The median follow-up of only 24 weeks may be too short to detect differences that emerge over longer treatment. Electronic health records may have incomplete outcome capture. The study compared clinical events but did not assess weight loss, symptom improvement, or quality of life, where differences between the drugs might exist."},{"rthcId":"RPEP-15736","title":"Preclinical Heart Failure: A Dynamic Trajectory of Progression, Regression, and Risk.","authors":"Moore, Ashe; Wong, Bethany; Brennan, Alice; Zhou, Shuaiwei; McCambridge, Joseph; Barrett, Matthew; Watson, Chris; Gallagher, Joseph; Ledwidge, Mark; McDonald, Kenneth","year":2026,"journal":"Journal of the American Heart Association, 15(4), e043944","doi":"10.1161/JAHA.125.043944","pmid":"41669963","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15737","title":"Weekly Liraglutide for the Management of Intractable Polydipsia and Interdialytic Weight Gain in a Patient on Hemodialysis: A Case Report.","authors":"Mora-Bravo, Franklin; Morales, Pamela T; Pincay, Gabriela; Pineda, Samantha; Morales, Brayan","year":2026,"journal":"Cureus, 18(1), e102197","doi":"10.7759/cureus.102197","pmid":"41585614","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Weekly low-dose liraglutide (1.2 mg/week) reduced interdialytic weight gain from 5.72% to 2.72% and decreased thirst from 10/10 to 3/10 on an analog scale in a non-diabetic hemodialysis patient with refractory polydipsia. The treatment stabilized blood pressure and improved dialysis tolerance in a patient whose management was severely limited by baseline hypotension and hemodynamic instability. The mechanism is proposed to be GLP-1 receptor-mediated modulation of neural circuits controlling thirst, independent of glycemic effects.","whyItMatters":"Fluid overload from uncontrollable thirst is a dangerous and common problem in dialysis patients with no good treatments. This case demonstrates an entirely novel use of a GLP-1 peptide drug — not for diabetes or weight loss, but as a thirst suppressant targeting brain circuits that regulate drinking behavior. It reframes non-compliance with fluid restrictions as a treatable neuroendocrine condition rather than a behavioral failure.","specificNumbers":"Liraglutide 1.2 mg weekly · IDWG reduced 5.72%→2.72% · thirst 10/10→3/10 · previous peak IDWG 8% (6L) · non-diabetic patient · stabilized BP from 90/60 mmHg baseline","methodology":"Single case report of a 66-year-old woman with ESRD on chronic hemodiafiltration without residual kidney function. After refractory hypervolemia from intractable polydipsia, liraglutide 1.2 mg was initiated once weekly (intentionally below standard dosing). Interdialytic weight gain, thirst (visual analog scale), blood pressure, and dialysis tolerance were monitored.","limitations":"Single case report — cannot generalize to other patients. No control or comparison treatment. Weekly liraglutide dosing is off-label and non-standard (daily 1.2-1.8 mg is approved). The mechanism of thirst suppression is proposed but not directly demonstrated. Long-term safety of GLP-1 agonists in anuric ESRD patients not established. Published in Cureus, a lower-impact journal."},{"rthcId":"RPEP-15738","title":"Clinical Efficacy of a Flavo-Proxylane Topical Regimen Pre- and Post-ultrasound Procedure for Subjects Undergoing Glucagon-Like Peptide 1 (GLP-1) Receptor Agonist Therapy.","authors":"Moradi, Amir; Kim, Jihee H; Kim, Jemin M; Choudhary, Hina N; Brieva, Patricia M","year":2026,"journal":"Dermatology and therapy","doi":"10.1007/s13555-026-01699-w","pmid":"41781778","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15739","title":"Nonsurgical Aesthetic Treatment of the Face and Neck in GLP-1 Receptor Agonist Weight Loss Patients: Experience-Based Considerations.","authors":"Moradi, Amir; Denkova, Radina; Holcomb, Katherine; Rossi, Anthony; Ashourian, Nazanin","year":2026,"journal":"Aesthetic surgery journal. Open forum, 8, ojag011","doi":"10.1093/asjof/ojag011","pmid":"41768029","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15740","title":"Persistent postural-perceptual dizziness versus vestibular migraine: A narrative review.","authors":"Moreno-Ajona, David","year":2026,"journal":"Headache, 66(1), 298-306","doi":"10.1111/head.15078","pmid":"41147266","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15741","title":"DNA prime and peptide boost immunization elicits robust neoantigen-specific CD8 + T cell responses and therapeutic protection in mouse tumor models.","authors":"Morgado-Cáceres, Pablo; Hofmann-Vega, Francisca; Figueroa, Diego; Saavedra-Almarza, Juan; Gálvez-Cancino, Felipe; Díaz, Ximena; Menares, Evelyn; Roa, Eduardo; Hidalgo, Sofia; Varas-Godoy, Manuel; Borgna, Vincenzo; Lladser, Alvaro","year":2026,"journal":"Oncoimmunology, 15(1), 2606497","doi":"10.1080/2162402X.2025.2606497","pmid":"41521424","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The DNA prime-peptide boost immunization strategy elicited the strongest CD8+ T-cell responses compared to homologous DNA-only or peptide-only approaches. These T cells showed both effector and memory precursor phenotypes and formed circulating and skin-resident memory T cells.\n\nIn prophylactic settings, this regimen delayed B16F10 melanoma growth and rejected EL4 lymphoma cells expressing a self-antigen. Therapeutically, the DNA prime-peptide boost eliminated EL4 tumors expressing the neo-epitope model in most mice. When targeting two bona fide neoepitopes of the MC38 tumor model, the strategy elicited neoepitope-specific CD8+ T-cell responses and a marked therapeutic effect that could be enhanced by combining with anti-PD-1 antibody.","whyItMatters":"Personalized cancer vaccines targeting neoantigens are a promising frontier in immunotherapy, but finding the most effective vaccination strategy is critical. This study demonstrates that a heterologous DNA prime-peptide boost approach outperforms single-platform vaccines, offering a practical blueprint for designing more potent neoantigen-based cancer immunotherapies that could eventually translate to human clinical trials.","specificNumbers":"","methodology":"Researchers compared homologous (same vaccine type twice) and heterologous (DNA then peptide) immunization strategies in mouse models using a neoantigen model. They measured CD8+ T-cell responses, characterized T-cell phenotypes, and tested both prophylactic and therapeutic tumor settings using B16F10 melanoma, EL4 lymphoma, and MC38 tumor models in C57BL/6 mice.","limitations":"This study was conducted entirely in mouse models, and results may not directly translate to humans. The neoantigen models used are simplified compared to the complex mutational landscape of real human tumors. Specific numerical data on tumor rejection rates and T-cell expansion levels were described qualitatively in the abstract rather than with precise statistics. Long-term durability of the immune response was not fully characterized."},{"rthcId":"RPEP-15742","title":"The importance of treatment sequencing with SGLT2 inhibitors and GLP-1 receptor agonists combination for kidney function preservation in type 2 diabetes.","authors":"Morieri, Mario Luca; Vedovato, Monica; Bonora, Benedetta Maria; Fioretto, Paola; Fadini, Gian Paolo","year":2026,"journal":"Diabetes, obesity & metabolism","doi":"10.1111/dom.70445","pmid":"41480667","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15743","title":"Disposition and Absolute Bioavailability of Orally Administered Orforglipron in Healthy Participants.","authors":"Morse, Bridget L; Bhattachar, Shobha; Ma, Xiaosu; Coutant, David E; Czeskis, Boris; Nicoll, Clare; Cassidy, Kenneth C","year":2026,"journal":"Clinical pharmacology in drug development, 15(1), e1594","doi":"10.1002/cpdd.1594","pmid":"40888509","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15744","title":"Conopeptides as Modulators of Pain and Inflammation in Chemotherapy-Induced Peripheral Neuropathy by Targeting α7 and α9 Nicotinic Acetylcholine Receptors.","authors":"Mosayyebi, Bashir; Faradonbeh, Davood Rabiei; Hosseindoost, Saereh; Arsanjani, Amirhossein Akbarpour; Negahdari, Babak; Majedi, Hossein; Malekshahi, Ziba Veisi","year":2026,"journal":"Neurotoxicity research, 44(1), 3","doi":"10.1007/s12640-025-00778-8","pmid":"41499076","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review highlights α-conotoxins RgIA4 and GeXIVA[1,2] as lead candidates for CIPN treatment. These peptides specifically target α9-containing nicotinic acetylcholine receptors (nAChRs), which play critical roles in both neuronal excitability and inflammatory responses in peripheral and central sensory pathways.\n\nThese conopeptides demonstrate dual therapeutic mechanisms: direct blockade of pain signaling through ion channel modulation, and reduction of neuroinflammation through neuroimmune pathway modulation. In animal models of CIPN, these peptides have shown disease-modifying potential rather than just symptom relief. Recent peptide engineering advances have improved their cross-species compatibility, receptor selectivity, and serum stability for potential clinical development.","whyItMatters":"CIPN affects up to 70% of cancer patients receiving certain chemotherapy drugs and often persists long after treatment ends. There are no FDA-approved preventive therapies. Current pain management (gabapentin, duloxetine) offers only modest relief and doesn't address the underlying nerve damage. Conopeptides that both block pain and reduce the neuroinflammation driving nerve damage could be the first disease-modifying treatments for this condition.","specificNumbers":"","methodology":"This is a narrative review synthesizing published research on conopeptide pharmacology, nicotinic acetylcholine receptor biology in CIPN, animal model studies, and recent advances in peptide engineering for improved drug-like properties.","limitations":"As a review, this synthesizes existing preclinical research rather than presenting new data. Most evidence comes from animal models of CIPN, and the translation to human nerve pain is uncertain. Conopeptides face significant pharmacokinetic challenges including limited oral bioavailability, short half-lives, and potential immunogenicity. The specific clinical development timelines and regulatory paths for these peptides are not discussed."},{"rthcId":"RPEP-15745","title":"A Narrative Review on GLP-1 Receptor Agonists for Obesity in Older Women: Maximizing Weight Loss While Preserving Lean Mass.","authors":"Moscucci, Federica; Baratta, Francesco; Pastori, Daniele; Menichelli, Danilo; Mattioli, Anna Vittoria; Gallina, Sabina; Lospinuso, Ilaria; Sciomer, Susanna; Piccirillo, Gianfranco; Desideri, Giovambattista","year":2026,"journal":"Nutrients, 18(4)","doi":"10.3390/nu18040632","pmid":"41754149","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15746","title":"Incretin therapy and obesity: current and future pharmacologic possibilities.","authors":"Moss, Emory; Hawk, Kennedy; Lollis, Kathrine; Clements, Jennifer N","year":2026,"journal":"Canadian journal of physiology and pharmacology, 104, 1-6","doi":"10.1139/cjpp-2025-0151","pmid":"41499766","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15747","title":"Multiple Sclerosis With Migraine and Pyoderma Gangrenosum Treated With Ofatumumab and Erenumab.","authors":"Motegi, Haruhiko; Komatsu, Teppei; Onda, Asako; Sakai, Kenichiro; Iguchi, Yasuyuki","year":2026,"journal":"Cureus, 18(1), e101886","doi":"10.7759/cureus.101886","pmid":"41567695","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15748","title":"Dulaglutide as a Bridging Therapy Before Insulin for Diabetes Following Pancreatectomy on Congenital Hyperinsulinism.","authors":"Motegi, Sakura; Adachi, Masanori; Nagahara, Keiko; Ochi, Ayako; Ishida, Tatsuyuki; Mizuno, Katsumi","year":2026,"journal":"JCEM case reports, 4(1), luaf281","doi":"10.1210/jcemcr/luaf281","pmid":"41347115","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15749","title":"Incretin effect is sufficient for glucose control in developing rats.","authors":"Motokura, Kouji; Tomotaki, Seiichi; Tomobe, Yutaro; Takita, Junko; Kawai, Masahiko","year":2026,"journal":"The Journal of endocrinology, 268(1)","doi":"10.1530/JOE-25-0146","pmid":"41503805","tags":[],"studyType":"animal-study","evidenceStrength":"low-moderate","keyFinding":"The incretin effect — where gut hormones boost insulin secretion after eating — is fully functional in developing 2-week-old rat pups, with an incretin effect of 63% (meaning 63% of the insulin response to oral glucose came from gut-stimulated incretin hormones rather than glucose alone).\n\nCritically, when the researchers gave standard therapeutic doses of a DPP-4 inhibitor (linagliptin) or a GLP-1 receptor agonist (liraglutide) to the pups, neither drug caused dangerous drops in blood sugar. This is significant because hypoglycemia is the major concern when treating high blood sugar in preterm infants.\n\nThe findings suggest that incretin-based therapies could be a safer approach to treating hyperglycemia in extremely premature babies compared to insulin, which carries substantial hypoglycemia risk.","whyItMatters":"Extremely premature babies frequently develop dangerously high blood sugar, but treating them with insulin is risky because it can cause hypoglycemia — which can damage the developing brain. If incretin-based drugs (GLP-1 agonists or DPP-4 inhibitors) can lower blood sugar without causing hypoglycemia in developing organisms, they could offer a much safer treatment option for this vulnerable population.","specificNumbers":"Incretin effect: 63% · 2-week-old Wistar rat pups · Linagliptin and liraglutide tested · 0 hypoglycemic events · OGTT vs IPGTT comparison","methodology":"Researchers performed oral glucose tolerance tests (OGTT) and intraperitoneal glucose tolerance tests (IPGTT) in 2-week-old Wistar rat pups, comparing serum glucose, insulin, and incretin hormone levels between the two routes. They then administered standard therapeutic doses of linagliptin (DPP-4 inhibitor) and liraglutide (GLP-1 agonist) to developing pups and monitored for hypoglycemia.","limitations":"This is an animal study in rats — results may not directly translate to human preterm infants, whose metabolic systems differ from rodents. The 2-week-old rat pup is an imperfect model for human prematurity. No hyperglycemic model was tested — the drugs were given to normal pups, not to pups with the kind of hyperglycemia seen in preterm infants. Clinical trials in neonates would be needed before any treatment recommendation."},{"rthcId":"RPEP-15750","title":"Predicting Weight Outcomes From Obesity Medications in a Paediatric Population.","authors":"Mottalib, Md Mozaharul; Beheshti, Rahmatollah; Viswanathan, Karthik; Bunnell, H Timothy; Phan, Thao-Ly T","year":2026,"journal":"Pediatric obesity, 21(2), e70089","doi":"10.1111/ijpo.70089","pmid":"41679912","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15751","title":"Semaglutide Protects Retinal Ganglion Cells Against Rotenone-Induced Degeneration via Improved Glucose Metabolism.","authors":"Mouhammad, Zaynab A; Tribble, James R; Nicol, Alan; Andreopoulou, Evgenia; García-Bermúdez, Mariana Y; Aldana, Blanca I; Vohra, Rupali; Kolko, Miriam; Williams, Pete A","year":2026,"journal":"Investigative ophthalmology & visual science, 67(2), 25","doi":"10.1167/iovs.67.2.25","pmid":"41665299","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15752","title":"Human DRG Glucocorticoid Receptor Profiling Reveals Targets for Regionally Delivered Steroid Analgesia.","authors":"Mousa, Shaaban A; Metwally, Elsayed Y; Li, Xiongjuan; Tafelski, Sascha; Retana Romero, Oscar Andrés; Piontek, Jörg; Treskatsch, Sascha; Schäfer, Michael; Shaqura, Mohammed","year":2026,"journal":"Cells, 15(3)","doi":"10.3390/cells15030223","pmid":"41677592","tags":[],"studyType":"translational (human tissue + animal + clinical)","evidenceStrength":"moderate","keyFinding":"Glucocorticoid receptors (GR) are abundantly expressed in human dorsal root ganglion (DRG) sensory neurons — the same neurons that produce CGRP, the key pain-signaling neuropeptide. Specifically, GR was found to co-localize extensively with CGRP in pain-sensing C-fibers and Aδ-fibers, and was concentrated in medium-diameter neurons (40-65 μm). In animal models, GR activation reduced inflammatory pain through rapid non-genomic mechanisms, while mineralocorticoid receptors (MR) had the opposite effect — promoting pain. Clinically, epidural steroid injections provided at least 3 months of pain relief in patients with chronic radicular pain. Together, the findings suggest that steroids relieve pain partly by acting on GR in CGRP-producing pain neurons, and that MR blockade could enhance this effect.","whyItMatters":"Epidural steroid injections are among the most common procedures for chronic back and nerve pain, yet the molecular basis for how steroids relieve pain at the spinal level has been poorly understood. This study provides the first comprehensive human tissue evidence that steroid receptors are concentrated specifically on CGRP-producing pain neurons — revealing a direct link between steroid therapy and the peptide signaling system that drives pain. The discovery that MR has an opposing, pain-promoting effect opens a new therapeutic angle: combining GR activation with MR blockade could improve steroid-based pain treatments.","specificNumbers":"GR colocalized with CGRP in C-fibers and Aδ-fibers · Medium-diameter neurons (40-65 μm) · ≥3 months clinical analgesia · GR = pain-reducing · MR = pain-promoting","methodology":"Multi-approach translational study: (1) mRNA profiling and immunofluorescence confocal microscopy of human and rat DRG tissue to map GR and MR expression relative to pain markers including CGRP; (2) preclinical experiments in rat pain models testing GR activation and MR blockade on inflammatory pain via rapid non-genomic mechanisms; (3) clinical evaluation of transforaminal plus caudal epidural steroid injection in patients with chronic radicular pain, assessing analgesia duration.","limitations":"The human tissue component is descriptive (expression mapping) rather than functional. The clinical component appears observational rather than a controlled trial. The study doesn't directly demonstrate that GR activation reduces CGRP release in human DRG — this link is inferred from colocalization. The 3-month clinical follow-up is relatively short for chronic pain. The number of human DRG samples analyzed and the clinical patient cohort size are not specified in the abstract."},{"rthcId":"RPEP-15753","title":"Rabies lyssavirus phosphoprotein possesses RNA duplex-unwinding activities.","authors":"Mu, Jingfang; Wang, Caiqian; Shu, Ting; Xiong, Xiaobei; Ren, Yujie; Gong, Rui; Zhao, Ling; Zhou, Xi","year":2026,"journal":"Molecular therapy. Nucleic acids, 37(1), 102863","doi":"10.1016/j.omtn.2026.102863","pmid":"41783789","tags":[],"studyType":"laboratory","evidenceStrength":"low","keyFinding":"Researchers discovered that the rabies virus phosphoprotein (RABV-P) has previously unknown RNA-unwinding activities — both helicase-like (energy-dependent) and chaperone-like (energy-independent). This is the first such activity identified in any rhabdovirus.\n\nCritically, two designed peptides (P90 and P110) targeting the protein's oligomerization domain effectively inhibited rabies virus replication in cells, demonstrating a new therapeutic strategy against this nearly 100% fatal disease.","whyItMatters":"Rabies kills approximately 59,000 people annually and is nearly 100% fatal once symptoms appear. There are no effective antivirals. Discovering a new druggable target on the rabies virus — and showing that peptides can block it — opens a completely new therapeutic approach for one of the deadliest known viruses.","specificNumbers":"2 peptides designed (P90, P110) · First RNA-unwinding activity in Rhabdoviridae · C-terminal domain + COD required · Effective cell-based inhibition","methodology":"Laboratory study combining biochemical characterization of RABV phosphoprotein's RNA-unwinding activities with peptide inhibitor design. RNA duplex-unwinding and annealing assays characterized the enzymatic activities. Two peptides targeting the central oligomerization domain (COD) were designed and tested for antiviral activity in cell-based rabies virus replication assays.","limitations":"Entirely in vitro and cell-based — no animal model testing. Peptide stability, delivery to the nervous system (where rabies replicates), and in vivo efficacy were not assessed. Rabies virus primarily infects neurons, which are challenging drug targets. The peptides' effectiveness against different rabies strains was not evaluated."},{"rthcId":"RPEP-15754","title":"Biometallic peptide-drug conjugates in photo-crosslinkable hydrogels enable combined photothermal-chemotherapy against breast cancer.","authors":"Mu, Rongqiu; Gu, Guanghui; Wang, Xinyue; Wang, Ranran; Wei, Gang","year":2026,"journal":"Journal of nanobiotechnology","doi":"10.1186/s12951-026-04081-2","pmid":"41668037","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15755","title":"Ecological and functional dynamics of gut microbiota in the model insect, silkworm Bombyx mori.","authors":"Muhammad, Abrar; Sun, Chao; Shao, Yongqi","year":2026,"journal":"World journal of microbiology & biotechnology, 42(1), 39","doi":"10.1007/s11274-026-04784-6","pmid":"41528513","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15756","title":"Semaglutide augments vascular proliferation and cardiac performance in a large animal model of ischemic cardiomyopathy.","authors":"Muir, Kelsey C; Stone, Christopher; Harris, Dwight D; Kanuparthy, Meghamsh; Broadwin, Mark; Hamze, Jad; Feng, Jun; Sellke, Frank W","year":2026,"journal":"American journal of physiology. Heart and circulatory physiology, 330(3), H651-H663","doi":"10.1152/ajpheart.00828.2025","pmid":"41553720","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Sixteen Yorkshire swine with diet-induced metabolic syndrome and surgically induced coronary artery disease were randomized to semaglutide (n=8) or control (n=8) for 5 weeks. Semaglutide-treated animals showed significantly improved left ventricular filling, end diastolic volume, stroke volume, and cardiac index (all p<0.05).\n\nThe mechanism was identified as enhanced vascular proliferation in the peri-ischemic myocardium — semaglutide stimulated growth of collateral blood vessels around the blocked coronary artery. Coronary arteriole vasoactivity was also improved, with enhanced vessel relaxation. Molecular analysis revealed pro-angiogenic pathway activation in the ischemic territory, including changes in proteins involved in blood vessel formation. The study provides the first mechanistic evidence that GLP-1 receptor agonism directly improves coronary collateralization in the setting of chronic ischemic cardiomyopathy.","whyItMatters":"Coronary artery disease is the leading cause of death worldwide. While procedures like stenting and bypass surgery open blocked arteries, many patients have disease too diffuse or vessels too small for intervention. Semaglutide's ability to stimulate the heart to grow its own new blood vessels could provide a pharmaceutical alternative — or complement — to surgical revascularization, especially for the millions of diabetic and obese patients who already qualify for GLP-1 therapy.","specificNumbers":"","methodology":"Sixteen Yorkshire swine were fed a high-fat diet for 5 weeks to induce metabolic syndrome, then underwent ameroid constrictor placement to create focal coronary artery disease. Animals were randomized to oral semaglutide (n=8, 4 male, 4 female) or no drug (n=8) for 5 weeks. Terminal evaluation included left ventricular pressure-volume catheterization, coronary collateral characterization, mounted coronary arteriole vasoactivity testing, and molecular analysis of ischemic myocardium using immunoblotting, immunofluorescence, and proteomics.","limitations":"This was a relatively small animal study (8 per group) with a short treatment duration (5 weeks). The ameroid constrictor model produces gradual coronary occlusion, which differs from the acute plaque rupture events that cause most human heart attacks. Pigs, while physiologically similar to humans, are not identical in coronary anatomy or metabolic response. The high-fat diet metabolic syndrome model may not fully recapitulate long-standing human diabetes. Whether these vascular changes would persist or continue to improve with longer treatment is unknown."},{"rthcId":"RPEP-15757","title":"The 'Obesity First' approach: Redefining the future of healthcare.","authors":"Mulder, Chris J J; Bayoumy, Ahmed B; Ansari, Azhar R","year":2026,"journal":"Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology, 45(1), 15-19","doi":"10.1007/s12664-025-01882-5","pmid":"41152558","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15758","title":"Injured cardiac targeting magnetic nanovesicles for mRNA treatment of myocardial infarction.","authors":"Mun, Dasom; Kang, Ji-Young; Park, Malgeum; Yoo, Gyeongseo; Lee, Jaewoong; Yun, Nuri; Joung, Boyoung","year":2026,"journal":"Theranostics, 16(8), 4090-4112","doi":"10.7150/thno.124754","pmid":"41695467","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15759","title":"Potential Eye Disorders in People With and Without Type 2 Diabetes Mellitus Exposed to GLP-1 Receptor Agonists: An Examination of the FAERS (FDA Adverse Event Reporting System) Database.","authors":"Murray, Mya; Schifano, Fabrizio; Chiappini, Stefania; Corkery, John Martin; Guirguis, Amira","year":2026,"journal":"American journal of ophthalmology, 283, 279-290","doi":"10.1016/j.ajo.2025.12.015","pmid":"41429246","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15760","title":"Echinomycin, a peptide antibiotic from a new bacterial source and its potential to tackle drug resistance in methicillin-resistant Staphylococcus aureus.","authors":"Murtaza, Mohd; Bhasin, Nitika; Kumari, Priya; Kour, Avleen; Choudhary, Poonam; Kushwaha, Manoj; Sharma, Sandeep; Jaglan, Sundeep","year":2026,"journal":"Archives of microbiology, 208(3), 136","doi":"10.1007/s00203-025-04699-0","pmid":"41563479","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A Streptomyces pratensis strain (S26-11) isolated from Himalayan soil in Kargil, Ladakh was identified as a new production source for echinomycin. This is the first report of S. pratensis producing echinomycin.\n\nThe study provided the first demonstration of echinomycin-mediated modulation of key genes associated with Staphylococcus aureus biofilm formation and pathogenicity. When piperine was used as an adjuvant, it lowered echinomycin's minimum inhibitory concentration (MIC) and potentially limited the emergence of resistant MRSA mutants, suggesting reduced risk of antimicrobial resistance development.","whyItMatters":"MRSA infections cause tens of thousands of deaths annually, and resistance to existing antibiotics continues to grow. Discovering new natural sources of peptide antibiotics and demonstrating novel mechanisms of action (biofilm disruption, gene modulation) addresses both the supply and efficacy challenges in the fight against antimicrobial resistance.","specificNumbers":"","methodology":"The bacterial strain was isolated from soil collected in Kargil, Ladakh (NW Himalayas) and identified through morphological analysis and 16S rDNA phylogenetic sequencing. Echinomycin was purified from ethyl acetate extracts and identified by chemical analysis. Antimicrobial activity was tested against MRSA, with gene expression analysis for biofilm and pathogenicity-related genes. Combination studies with piperine assessed synergistic effects and resistance development potential.","limitations":"All findings are from in vitro experiments and have not been validated in animal models or clinical settings. The authors specifically note that further validation with clinical MRSA strains, detailed dose-response studies, and in vivo experiments are needed. Echinomycin's known cytotoxicity may limit its therapeutic window in humans. Production scalability from this new source has not been assessed."},{"rthcId":"RPEP-15761","title":"Divergent effect of diabetes on fibrosis response to semaglutide and resmetirom in noncirrhotic MASH: A meta-analysis of randomized trials.","authors":"Musso, Giovanni; Pinach, Silvia; Cassader, Maurizio; Mariano, Filippo; Gambino, Roberto","year":2026,"journal":"Med (New York, N.Y.), 7(2), 100959","doi":"10.1016/j.medj.2025.100959","pmid":"41610839","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15762","title":"Neurologic Complications of Endocrine Disorders.","authors":"Mustafa, Rafid","year":2026,"journal":"Continuum (Minneapolis, Minn.), 32(1), 105-130","doi":"10.1212/cont.0000000000001658","pmid":"41631909","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15763","title":"Synthesis and Characterization of Thermostable Antimicrobial Peptide-DNAzyme Conjugates for the Proof-of-Concept Detection of E. coli.","authors":"Mutter, Natalie; Savini, Filippo; Ban, Željka; Saftić, Dijana Pavlović; Hloušek-Kasun, Andrea; Ahmadi, Yasaman; Bertoša, Branimir; Piantanida, Ivo; Barišić, Ivan","year":2026,"journal":"ACS omega, 11(5), 8024-8033","doi":"10.1021/acsomega.5c10306","pmid":"41696256","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15764","title":"Emerging incretin- and multi-agonist-based treatments - the continued refinement and continuous expansion of a potent therapeutic armamentarium for cardio-kidney-liver-metabolic diseases and beyond.","authors":"Muzurović, Emir; Katsiki, Niki; Volčanšek, Špela; Plescia, Fulvio; Rizzo, Manfredi; Mantzoros, Christos S","year":2026,"journal":"Metabolism: clinical and experimental, 177, 156494","doi":"10.1016/j.metabol.2026.156494","pmid":"41564595","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15765","title":"False nonresponders to anti-calcitonin gene-related peptide monoclonal antibodies: A real-world analysis beyond migraine frequency reduction.","authors":"Muñoz-Vendrell, Albert; Campoy-Díaz, Sergio; Díaz-Corta, Patricia; Termens, Lidia; Campdelacreu, Jaume; Prat, Joan; Sanahuja, Jordi; Huerta-Villanueva, Mariano","year":2026,"journal":"Headache, 66(1), 172-182","doi":"10.1111/head.70012","pmid":"41316702","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15766","title":"Effects of cecropin A on cytokine production and tight junction protein expression in chicken ileal explant cultures.","authors":"Márton, Rege Anna; Varga, Olivér; Vincent, Naveen Joseph; Tráj, Patrik; Sebők, Csilla; Kemény, Ágnes; Mackei, Máté; Neogrády, Zsuzsanna; Molnár-Nagy, Viviána; Mátis, Gábor","year":2026,"journal":"Veterinary research communications, 50(2), 104","doi":"10.1007/s11259-025-11046-7","pmid":"41537918","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15767","title":"Effects of cecropin A on cytokine production and tight junction protein expression in chicken ileal explant cultures.","authors":"Márton, Rege Anna; Varga, Olivér; Vincent, Naveen Joseph; Tráj, Patrik; Sebők, Csilla; Kemény, Ágnes; Mackei, Máté; Neogrády, Zsuzsanna; Molnár-Nagy, Viviána; Mátis, Gábor","year":2026,"journal":"Veterinary research communications, 50(2), 104","doi":"10.1007/s11259-025-11046-7","pmid":"41537918","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Cecropin A (an insect-derived antimicrobial peptide) showed immunomodulatory effects in chicken ileal explant cultures without cytotoxicity. At the higher dose (6.25 µg/mL), it increased IL-2 production (an immune activation signal) and elevated claudin-3 expression (a tight junction protein that strengthens the gut barrier). Under inflammatory conditions (Poly I:C challenge), the lower dose of cecropin A (3.125 µg/mL) reduced IL-6 (an inflammatory cytokine). Cell viability remained unaffected at both doses.","whyItMatters":"Antibiotic resistance is a growing crisis in livestock farming, where antibiotics have long been used to promote growth and prevent disease. Antimicrobial peptides like cecropin A could serve as alternatives — this study shows cecropin A can modulate the chicken immune system, reduce inflammation, and strengthen the gut barrier without killing cells. If effective in live animals, peptide-based feed additives could reduce antibiotic use in poultry farming.","specificNumbers":"CecA: 3.125 and 6.25 µg/mL · Poly I:C: 50 µg/mL · IL-2 increased (6.25 µg/mL) · IL-6 decreased (under inflammation) · Claudin-3 increased · No cytotoxicity","methodology":"Ex vivo chicken ileal explant cultures treated with cecropin A at two concentrations (3.125 and 6.25 µg/mL) with or without Poly I:C (a synthetic inflammatory stimulus). Endpoints: cell viability (metabolic activity, LDH release), cytokine production (IL-2, IL-6), and tight junction protein expression (claudin-3). This ex vivo approach preserves the tissue architecture of the gut while allowing controlled peptide exposure.","limitations":"This is an ex vivo study using tissue explants, not live chickens. The artificial inflammatory stimulus (Poly I:C) doesn't perfectly replicate natural pathogen exposure. Only two concentrations were tested. Long-term effects and whether cecropin A survives passage through the chicken digestive system when given orally are unknown. Results in poultry may not translate to other species."},{"rthcId":"RPEP-15768","title":"A C. elegans model of familial Alzheimer's disease shows age-dependent synaptic degeneration independent of amyloid β-peptide.","authors":"Nagarajan, Vaishnavi; Libowitz, Caitlin L; Ackley, Brian D; Wolfe, Michael S","year":2026,"journal":"Neurobiology of disease, 219, 107267","doi":"10.1016/j.nbd.2026.107267","pmid":"41525885","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15769","title":"Predicting survival in patients with heart failure aged 80 years and older.","authors":"Nagata, Takuya; Tohyama, Takeshi; Ikeda, Masataka; Watanabe, Hiroko; Kaku, Hidetaka; Enzan, Nobuyuki; Matsushima, Shouji; Fujino, Takeo; Hashimoto, Toru; Takemoto, Masao; Ide, Tomomi; Tsutsui, Hiroyuki; Abe, Kohtaro","year":2026,"journal":"ESC heart failure, 13(1)","doi":"10.1093/eschf/xvag033","pmid":"41711736","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15770","title":"Increased cholesterol interactions in the active conformational state of the glucagon-like peptide-1 receptor.","authors":"Naglekar, Amit; Chattopadhyay, Amitabha; Sengupta, Durba","year":2026,"journal":"Biophysical journal, 125(2), 546-556","doi":"10.1016/j.bpj.2025.09.003","pmid":"40913315","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Coarse-grained molecular dynamics simulations of GLP-1R in four conformational states revealed that cholesterol hotspots vary between receptor states, with increased cholesterol enrichment around the receptor in active conformational states. Active states showed more favorable cholesterol interaction energetics and increased residence times compared to inactive and partially active states.\n\nSubtle differences were observed between GLP-1-bound and exenatide-bound receptor states, highlighting ligand-specific effects on cholesterol interactions. The findings demonstrate that cholesterol selectively associates with the active state of GLP-1R, suggesting that membrane cholesterol content could modulate receptor signaling.","whyItMatters":"Cholesterol levels vary between cell types and disease states (including the metabolic conditions GLP-1 drugs treat). If cholesterol modulates GLP-1 receptor activation, then a patient's cholesterol status could affect how well their GLP-1 drug works. This study provides the first detailed map of cholesterol-receptor interactions across the activation cycle, opening a new dimension for drug design.","specificNumbers":"","methodology":"Coarse-grained molecular dynamics simulations were performed on the GLP-1 receptor in four conformational states: inactive, partially active, GLP-1-bound active, and exenatide-bound active. Cholesterol interaction hotspots, interaction energetics, and residence times were characterized for each state and compared across the activation cycle.","limitations":"Coarse-grained simulations sacrifice atomic-level detail for computational efficiency. The findings are computational predictions that require experimental validation. The simulations may not capture all relevant aspects of the complex cellular membrane environment. How cholesterol interactions translate to measurable differences in drug efficacy in patients remains to be determined."},{"rthcId":"RPEP-15771","title":"A helical peptide antagonist of the human growth hormone receptor.","authors":"Nahar, Khairun; Basu, Reetobrata; Ahmad, Arshad; Pettis, Joseph; Gamage, Udani; Holub, Justin M; Kopchick, John J","year":2026,"journal":"Endocrinology","doi":"10.1210/endocr/bqag022","pmid":"41742787","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15772","title":"Molecular Materials as Fluorescent Nano Gene Silencers: Peptide Gold Cluster as Promising Cancer Theranostics.","authors":"Nair, Resmi V; Santhakumar, Hema; Govindachar, Divya Maldepalli; Modi, Jitendra; Subramani, Sivaselvam; Periyasamy, Ganga; Ueda, Motoki; Ito, Yoshihiro; Jayasree, Ramapurath S","year":2026,"journal":"Small (Weinheim an der Bergstrasse, Germany), 22(11), e06474","doi":"10.1002/smll.202506474","pmid":"41470012","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Ultrasmall (~3 nm) oligopeptide-stabilized gold nanoclusters functionalized with survivin-targeting siRNA and Her2 antibodies outperformed the commercial transfection agent Lipofectamine2000 in delivering gene-silencing therapy to breast cancer cells. The system achieved potent survivin knockdown, significant reduction in cell proliferation, and served as a fluorescent imaging agent for real-time tracking — all without triggering cytotoxicity.","whyItMatters":"Cancer cells evade death by overproducing survivin, a key anti-apoptotic protein. This peptide-based nanoplatform simultaneously targets survivin with gene silencing, tracks delivery with fluorescent imaging, and selects cancer cells via Her2 antibodies — combining diagnosis and treatment in one nanoparticle. Outperforming Lipofectamine2000 suggests practical superiority over existing siRNA delivery methods.","specificNumbers":"~3 nm gold nanoclusters · red-fluorescent emission · outperformed Lipofectamine2000 · survivin knockdown · reduced proliferation · no cytotoxicity · SK-BR-3 breast cancer cells","methodology":"Oligopeptide-stabilized gold nanoclusters were synthesized and characterized for size, fluorescence, and stability. Nanoclusters were functionalized with survivin-targeting siRNA and Her2-specific antibodies. Cellular uptake, siRNA delivery efficiency, survivin gene silencing, cell proliferation, and cytotoxicity were assessed in Her2-positive SK-BR-3 breast cancer cells, with Lipofectamine2000 as the benchmark comparison.","limitations":"In vitro study using a single breast cancer cell line (SK-BR-3). No in vivo tumor model tested. Limited to Her2-positive cancers. Long-term biocompatibility and biodistribution of gold nanoclusters not assessed. Scalability and manufacturing complexity of the multi-component system may be challenging."},{"rthcId":"RPEP-15773","title":"Evaluation of antioxidant activities of bioactive peptides extracted from Curcuma longa and Curcuma caesia from South-eastern and North-Eastern India.","authors":"Narayanasamy, Anshula; Kanagaraja, Abinaya; Thirumavalavan, Munusamy; Sakthivelu, Meenakumari; Pachaiappan, Raman","year":2026,"journal":"Probiotics and antimicrobial proteins","doi":"10.1007/s12602-025-10895-7","pmid":"41636981","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15774","title":"Multitarget Amaranth Peptides: ACE Inhibition, ACE2 Modulation, and Bioavailability Assessment.","authors":"Nardo, Agustina E; Suárez, Santiago E; García Fillería, Susan F; Añón, M Cristina; Quiroga, Alejandra V","year":2026,"journal":"Plant foods for human nutrition (Dordrecht, Netherlands), 81(1), 7","doi":"10.1007/s11130-025-01456-y","pmid":"41518456","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Two amaranth-derived peptides, SFNLPILR and FNLPILR, demonstrated potent ACE inhibition with IC₅₀ values of 0.075 mM and 0.055 mM, respectively. Both peptides showed selective or minimal modulation of ACE2 enzymatic activity, suggesting they can suppress the harmful arm of the renin-angiotensin system while preserving the protective arm.\n\nMolecular docking revealed that both peptides interact with ACE's catalytic residues through their shared LR motif. Transepithelial transport studies using Caco-2 cell monolayers confirmed that peptide fragments can cross the intestinal barrier, supporting potential oral bioavailability.","whyItMatters":"Hypertension affects over a billion people worldwide and is a leading cause of heart disease and stroke. Food-derived bioactive peptides that can inhibit ACE offer a natural, preventive approach to blood pressure management. Identifying peptides that both inhibit ACE and cross the gut barrier brings the concept of 'blood pressure-lowering food' closer to scientific reality.","specificNumbers":"","methodology":"The study combined multiple approaches: in vitro enzymatic assays to measure ACE inhibition and ACE2 modulation; bioinformatic analysis to identify encrypted bioactive motifs within the peptide sequences; molecular docking simulations to model how the peptides bind to ACE's active site; and Caco-2 cell monolayer transepithelial transport studies to assess whether peptide fragments can cross the intestinal barrier (a standard model for oral bioavailability).","limitations":"This is an in vitro and computational study — the peptides have not been tested in animals or humans for actual blood pressure reduction. The Caco-2 transport studies showed that peptide fragments (not intact peptides) cross the intestinal barrier, so the active forms reaching the bloodstream may differ from what was tested. IC₅₀ values in vitro may not predict clinical potency. The third peptide (AFEDGFEWVSFK) was not as well characterized."},{"rthcId":"RPEP-15775","title":"JAAD CME Part 1: Mechanism of Action of GLP-1 Receptor Agonists and Potential Pathways in Skin Health.","authors":"Narla, Shanthi; Narla, Radhika R; Corbett, John A","year":2026,"journal":"Journal of the American Academy of Dermatology","doi":"10.1016/j.jaad.2026.01.088","pmid":"41707707","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"This CME review outlines several key points about GLP-1-based therapies and skin health:\n\n- GLP-1 receptors have broad cellular distribution, including in tissues relevant to skin biology\n- GLP-1 receptor agonists attenuate pro-inflammatory cytokine signaling while promoting anti-inflammatory pathways\n- Emerging evidence supports relevance in dermatology for:\n  - Improvement in psoriasis\n  - Improvement in hidradenitis suppurativa (HS)\n  - Enhanced wound healing\n  - Modulation of nociceptive (pain) signaling\n- Dual GLP-1/GIP receptor agonists (like tirzepatide) may have additional mechanisms beyond single GLP-1 agonists\n- The immunomodulatory effects are mechanistically distinct from the metabolic effects","whyItMatters":"Millions of dermatology patients with psoriasis and hidradenitis suppurativa need better treatment options. Many of these patients also have metabolic comorbidities like obesity and type 2 diabetes. If GLP-1 medications can simultaneously address metabolic disease and inflammatory skin conditions, they could transform the treatment approach for patients with overlapping conditions — treating the whole patient rather than individual diseases in isolation.","specificNumbers":"","methodology":"This is a narrative review and CME article published in the Journal of the American Academy of Dermatology. It synthesizes the historical development, mechanisms of action, and emerging dermatological evidence for GLP-1 receptor agonists and dual GLP-1/GIP agonists.","limitations":"As a review article, this paper synthesizes emerging evidence without presenting new data. The dermatological evidence for GLP-1 RAs is still early-stage, consisting largely of case reports, small series, and observational data rather than randomized controlled trials. The mechanisms linking GLP-1 receptor activation to skin health are not fully elucidated. Weight loss itself could explain some skin improvements in psoriasis and HS, making it difficult to separate direct skin effects from indirect metabolic benefits."},{"rthcId":"RPEP-15776","title":"JAAD CME Part 2: Clinical Evidence and Safety Considerations for GLP-1 Receptor Agonists in Dermatology.","authors":"Narla, Shanthi; Narla, Radhika R","year":2026,"journal":"Journal of the American Academy of Dermatology","doi":"10.1016/j.jaad.2025.12.116","pmid":"41698604","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Early clinical evidence from case reports, small cohorts, and short-duration trials suggests GLP-1 RAs may benefit several dermatologic conditions:\n- Psoriasis: reductions in Psoriasis Area and Severity Index (PASI) scores\n- Hidradenitis suppurativa (HS): improved disease activity and patient-reported symptoms\n- Wound healing: fewer wound complications in retrospective datasets\n\nThese effects likely reflect both direct immunomodulation and indirect metabolic benefits (weight loss and reduced systemic inflammation). However, GLP-1 RAs can also cause dermatologic adverse events including pruritus (itching), drug eruptions, alopecia (hair loss), and acne, in addition to systemic side effects like gastrointestinal intolerance and biliary disease.","whyItMatters":"Millions of patients are now taking GLP-1 peptide drugs for diabetes and obesity. Dermatologists need to understand both the potential skin benefits and dermatologic side effects. If confirmed in larger trials, the anti-inflammatory properties of these peptides could offer an additional treatment avenue for chronic inflammatory skin diseases that are often challenging to manage — particularly in patients who already have metabolic comorbidities.","specificNumbers":"","methodology":"This is a continuing medical education (CME) review article published in JAAD (Journal of the American Academy of Dermatology), synthesizing available clinical evidence on GLP-1 receptor agonists in dermatologic applications. It covers case reports, small cohort studies, observational data, and short-duration trials, along with safety considerations.","limitations":"The evidence base is very limited — mostly case reports, small cohorts, and short-duration studies. Most patients in existing reports had comorbid diabetes or obesity, making it impossible to separate the direct skin effects of GLP-1 RAs from the indirect benefits of weight loss and metabolic improvement. There is significant heterogeneity in the GLP-1 agents, dosing protocols, and skin conditions studied. No large randomized controlled trials have been completed for any dermatologic indication."},{"rthcId":"RPEP-15777","title":"Repurposing GLP-1 receptor agonists for alcohol use disorder: a systematic review and meta-analysis.","authors":"Nasrollahizadeh, Amir; Kheiri, Ghazaleh; Javankiani, Sepide; Kheiri, Sadra; Hamzavi, Seyedeh Fatemeh; Karimi, Mehdi; Amini-Salehi, Ehsan; Karimi, Mohammad Amin","year":2026,"journal":"Diabetology & metabolic syndrome, 18(1), 29","doi":"10.1186/s13098-025-02006-x","pmid":"41508124","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15778","title":"TNF-α-mediated down-regulation of mitochondrial transcription factors: Rescue by Angiotensin-(1-7) peptide.","authors":"Natarajan, Bhargavi; Vijayakumar, Anupama; Iyer, Dhanya R; Venkatraman, Janani; Arige, Vikas; Khan, Abrar A; Barthwal, Manoj K; Kontos, Christopher; Mahapatra, Nitish R","year":2026,"journal":"Mitochondrion, 88, 102130","doi":"10.1016/j.mito.2026.102130","pmid":"41687755","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Mitochondrial transcription factors (Tfam, Tfb1m, Tfb2m) were significantly reduced in the left ventricle of spontaneously hypertensive rats (SHR) compared to normotensive controls (WKY). TNF-α treatment of H9c2 cardiomyoblasts similarly suppressed these mitochondrial transcription factors.\n\nAngiotensin-(1-7) reversed the TNF-α-mediated repression of all three mitochondrial transcription factors in vitro. The mechanism involved the PGC-1α-YY1 transcriptional complex: TNF-α prevented formation of this complex, allowing YY1 alone to repress mitochondrial transcription factor genes. Ang-(1-7) restored PGC-1α-YY1 complex formation, reactivating transcription. This establishes the PGC-1α-YY1 complex as a molecular switch and Ang-(1-7) as a regulator of cardiac mitochondrial biogenesis under inflammatory conditions.","whyItMatters":"Mitochondrial dysfunction is a central feature of heart failure caused by chronic hypertension, but the molecular mechanisms connecting inflammation to mitochondrial decline have been poorly understood. This study identifies a specific pathway — TNF-α disrupting PGC-1α-YY1 to silence mitochondrial genes — and shows that the peptide Ang-(1-7) can reverse it. This has direct therapeutic implications because Ang-(1-7) and its analogs are already being explored as cardiovascular drugs.","specificNumbers":"","methodology":"The study combined in vivo and in vitro approaches. Left ventricular tissue from spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) was analyzed for mitochondrial transcription factor expression. H9c2 cardiomyoblast cells were treated with TNF-α alone or TNF-α plus Angiotensin-(1-7) to assess effects on mtTF expression. Protein-protein interaction studies characterized the PGC-1α-YY1 complex formation under different treatment conditions. Gene expression and transcriptional activity were measured.","limitations":"The in vivo data comes from spontaneously hypertensive rats (a genetic model), which may not fully represent human hypertensive heart disease. The in vitro experiments used H9c2 cardiomyoblasts (a cell line), which differ from primary cardiomyocytes. The study demonstrates the mechanism in vitro but does not show that Ang-(1-7) restores mitochondrial function in hypertensive hearts in vivo. Specific concentrations and treatment durations were not detailed in the abstract. The translational potential to human heart failure requires further validation."},{"rthcId":"RPEP-15779","title":"GLP-1 Receptor Agonists in the Management of Post-bariatric Weight Regain and Dysglycemia: A Systematic Review and Meta-Analysis.","authors":"Natche, Julia; Olivas Lerma, Ricardo; Kanduri Hanumantharayudu, Sneha; Makam Surendraiah, Pavan Kumar; Rahman, Sharmin; Rahman, Farzana; Shah, Shivani; Bhatta, Mamta; Green, Siva Ranganathan; Sultana, Maria; Gul, Aiysha; Gairola, Pulkit","year":2026,"journal":"Cureus, 18(1), e102516","doi":"10.7759/cureus.102516","pmid":"41769499","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15780","title":"Intravesical substance P enhances bladder afferent nerve activity without the influence of the micturition reflex.","authors":"Natsuya, Hiroki; Fujita, Tomoe; Kojima, Yoshiyuki; Aizawa, Naoki","year":2026,"journal":"Naunyn-Schmiedeberg's archives of pharmacology, 399(1), 1287-1295","doi":"10.1007/s00210-025-04503-2","pmid":"40773011","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15781","title":"Dose-Escalation Regimens for Incretin Mimetics in Type 2 Diabetes Are Associated With Tolerance for Nausea and Vomiting.","authors":"Nauck, Michael A; Punov, Viktoria; Kang, Yu Mi; Lim, Soo","year":2026,"journal":"Diabetes, obesity & metabolism","doi":"10.1111/dom.70613","pmid":"41757397","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"For semaglutide (both subcutaneous and oral) and tirzepatide, the ED50 ratio (Phase 3 vs Phase 1) for nausea and vomiting was significantly greater than 1, confirming that dose escalation builds genuine physiological tolerance to gastrointestinal side effects.\n\nAcross all approved incretin-based medications, a higher ED50 ratio — indicating more tolerance development — was associated with longer drug escalation periods and a greater number of dose-escalation steps. Critically, this tolerance ratio was also significantly associated with larger reductions in HbA1c and body weight, demonstrating that tolerance enables higher therapeutic doses and better clinical outcomes.","whyItMatters":"Gastrointestinal side effects are the primary barrier to GLP-1 therapy adherence and dose optimization. This study provides the first systematic quantification of how dose-escalation strategies build tolerance, explaining why patients who titrate slowly can tolerate — and benefit from — higher final doses. The findings have immediate implications for optimizing titration schedules and could help reduce the high discontinuation rates seen with these medications.","specificNumbers":"","methodology":"Researchers compared nausea and vomiting rates from Phase 1 trials (no or short dose escalation) versus Phase 3 trials (with standard dose escalation) for approved GLP-1 receptor agonists and tirzepatide. Non-linear regression (curve fitting) was used to estimate the ED50 — the dose causing nausea or vomiting in 50% of subjects — for each trial phase. The ratio of Phase 3 to Phase 1 ED50 values served as the tolerance indicator. This ratio was then correlated with escalation regimen characteristics and therapeutic effect sizes.","limitations":"This is a cross-trial comparison using aggregate data from different studies with different populations, designs, and endpoints — not a randomized head-to-head comparison of escalation regimens. Phase 1 and Phase 3 trial populations differ (healthy volunteers vs. patients with diabetes), which could confound comparisons. The analysis focuses on nausea and vomiting but does not address other GI side effects like diarrhea or constipation. Individual patient-level tolerance trajectories are not captured."},{"rthcId":"RPEP-15782","title":"Glucagon-like receptor agonists and next-generation incretin-based medications: metabolic, cardiovascular, and renal benefits.","authors":"Nauck, Michael A; Tuttle, Katherine R; Tschöp, Matthias H; Blüher, Matthias","year":2026,"journal":"Lancet (London, England), 407(10531), 892-908","doi":"10.1016/S0140-6736(25)02105-1","pmid":"41547366","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 receptor agonists provide: highly effective glycemic control with low hypoglycemia risk; significant weight loss; reduced major adverse cardiovascular events (heart attack, stroke, cardiovascular death); reduced heart failure hospitalizations; reduced albuminuria and slowed eGFR decline (kidney protection); prevention of type 2 diabetes in obesity; regression of liver steatosis and prevention of fibrosis; and symptomatic improvement in obstructive sleep apnea and knee osteoarthritis.\n\nNext-generation developments include: dual GLP-1-glucagon and GLP-1-amylin agonists; triple GIP-GLP-1-glucagon agonists with greater weight loss potential; small-molecule oral GLP-1 agonists; and exploration of neurodegenerative disease and substance use disorder indications.","whyItMatters":"This Lancet review captures a historic moment in medicine: a single drug class transforming the treatment of multiple major diseases simultaneously. GLP-1 drugs are arguably the most impactful pharmaceutical development of the past decade, and next-generation multi-agonists may amplify these benefits further. Understanding the full scope of their proven and emerging applications is essential for every clinician.","specificNumbers":"","methodology":"Comprehensive narrative review published in The Lancet, synthesizing evidence from major clinical trials, cardiovascular outcome studies, and current development pipelines for GLP-1-based therapies.","limitations":"As a narrative review, this does not include systematic methodology or meta-analysis. Some mentioned benefits (neurodegenerative diseases, substance use disorders) have only suggestive evidence. Gastrointestinal adverse events remain a significant clinical challenge. Long-term safety data for the newest formulations is limited. Access and cost barriers are not addressed but represent major real-world implementation challenges."},{"rthcId":"RPEP-15783","title":"NBD Integrated and Vitamin B6-Driven Charge-Reversible Peptide-Based Nanocarriers for Targeted Therapeutic Delivery.","authors":"Nayak, Suman; Lye, Anushree; Guha, Subhabrata; Raghul, Nanjundan; Stewart, Adele; Das, Gaurav; Maity, Biswanath; Das, Priyadip","year":2026,"journal":"Small (Weinheim an der Bergstrasse, Germany), e13436","doi":"10.1002/smll.202513436","pmid":"41653423","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15784","title":"Xeno-Free Biocompatible Peptide-Based Bioinks Reinforced with Cellulose Nanofibers for 3D Printing.","authors":"Netti, Francesca; Tsuriano, Mor; Rattner, Noam; Altobelli, Vania; Dan, Yoav; Adler-Abramovich, Lihi","year":2026,"journal":"Advanced healthcare materials, 15(3), e01729","doi":"10.1002/adhm.202501729","pmid":"40908800","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15785","title":"Positive inotropic effects of glucose-dependent insulinotropic polypeptide in the human atrium and the mouse atrium.","authors":"Neumann, J; Hofmann, B; Gergs, U","year":2026,"journal":"Naunyn-Schmiedeberg's archives of pharmacology, 399(1), 1067-1077","doi":"10.1007/s00210-025-04485-1","pmid":"40715752","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15786","title":"Inotropic effects of retatrutide in isolated human atrial preparations.","authors":"Neumann, Joachim; Ahlrep, Undine; Hofmann, Britt; Gergs, Ulrich","year":2026,"journal":"Naunyn-Schmiedeberg's archives of pharmacology, 399(1), 317-327","doi":"10.1007/s00210-025-04421-3","pmid":"40613938","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15787","title":"Navigating the patient journey in migraine prevention: An American Migraine Foundation position paper.","authors":"Newman, Lawrence C; Lay, Christine; Lipton, Richard B; Ailani, Jessica; Digre, Kathleen B; Caplan, Arthur; Singh, Nim; Phillips, Heather; Koh, Rachel; Warrick, Royce; Dodick, David W","year":2026,"journal":"Headache, 66(2), 428-439","doi":"10.1111/head.15062","pmid":"41044874","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15788","title":"Semaglutide Use Is Associated With Decreased Length of Stay and Hospital Costs in Patients Undergoing Anterior Lumbar Interbody Fusion: A Retrospective Cohort Study.","authors":"Ng, Mitchell K; Mastrokostas, Paul G; Tabbaa, Ameer; Razi, Abigail; Johnson, Matthew; Said, Mohamed; Mastrokostas, Leonidas E; Dalton, Jonathan; Vaccaro, Alexander R; Kepler, Christopher K; Monsef, Jad Bou; Razi, Afshin E","year":2026,"journal":"Orthopedics, 49(1), e56-e61","doi":"10.3928/01477447-20251219-01","pmid":"41636429","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15789","title":"Helix stabilization by i,i + 7 amine-containing hydrocarbon Staples: Effects of length, stereochemistry, and orientation.","authors":"Nguyen, Ha T N; Lee, Su-Yeon; Tran, Duc V H; Kim, Young-Woo","year":2026,"journal":"Bioorganic & medicinal chemistry, 132, 118443","doi":"10.1016/j.bmc.2025.118443","pmid":"41106251","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A 13-atom butylaminoalkenyl tether with SS configuration was identified as the most effective i,i+7 ACH staple. Orientation reversal substantially enhanced helicity and this effect transferred across helical registers. The optimized staple conferred significant proteolytic resistance, linking structural preorganization to biochemical resilience.","whyItMatters":"Expanding the ACH stapling toolkit to i,i+7 topology enables longer-range helical control for therapeutic peptides targeting protein-protein interactions, with improved aqueous compatibility over conventional staples.","specificNumbers":"13-atom optimal tether length; SS stereochemistry; i,i+7 topology spanning 2 helical turns","methodology":"Systematic variation of cross-link length, stereochemistry, and orientation in model peptides. Helicity measured by circular dichroism spectroscopy. Proteolytic resistance tested against enzymatic degradation. Transferability confirmed across different helical register positions.","limitations":"This is a purely chemical study without biological activity data. The helicity measurements and proteolytic resistance were demonstrated in model peptides, not therapeutic candidates. Translation to specific disease-relevant peptides needs further validation. The study does not address cell permeability, in vivo stability, or pharmacokinetics of the stapled peptides."},{"rthcId":"RPEP-15790","title":"Topical Volumizing Cream Improves Facial Volume and Skin Health in Adults With Rapid Weight Loss From Pharmacologic (GLP-1/GIP Agonists), Surgical, or Behavioral Interventions.","authors":"Nguyen, Nhi; Aguilar, Alejandra; Afzal, Nasima; Lee, Andy; Akram, Wardah; Duong, Minh N; Sivamani, Raja K","year":2026,"journal":"Journal of cosmetic dermatology, 25(1), e70681","doi":"10.1111/jocd.70681","pmid":"41556403","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15791","title":"Combined associations of GLP-1 receptor agonists and a healthy lifestyle with cardiovascular outcomes among individuals with type 2 diabetes: a prospective cohort study.","authors":"Nguyen, Xuan-Mai T; Li, Yanping; Czernichow, Sébastien; Rassy, Nathalie; Houghton, Serena C; Lu, Bing; Ho, Yuk-Lam; Charest, Brian R; Wang, Dong D; Gagnon, David R; Gaziano, John Michael; Willett, Walter C; Wilson, Peter W F; Cho, Kelly; Hu, Frank B","year":2026,"journal":"The lancet. Diabetes & endocrinology","doi":"10.1016/S2213-8587(25)00395-X","pmid":"41763234","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15792","title":"Serial insulin and C-peptide concentrations following high-dose insulin for the treatment of drug poisoning: a consecutive case series.","authors":"Nic Ionmhain, Úna; Coulson, Lori; Roberts, Darren M","year":2026,"journal":"Clinical toxicology (Philadelphia, Pa.), 1-9","doi":"10.1080/15563650.2026.2613033","pmid":"41642277","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 10 poisoned patients treated with high-dose insulin, the median elimination half-life of insulin after discontinuation was 1.8 hours (IQR 1.4–4.0 h; range 1.23–9.8 h) — substantially shorter than previously reported values of up to 18.8 hours. The half-life was not significantly affected by insulin dosage, treatment duration, or kidney disease.\n\nC-peptide (a marker of the body's own insulin production) tracked with blood glucose levels despite the high external insulin, and concentrations remained mostly within normal reference ranges, suggesting that glucose supplementation during treatment was not excessive. Hyperinsulinemia typically resolved within 24 hours of stopping high-dose insulin.","whyItMatters":"High-dose insulin is used to treat life-threatening drug poisonings that cause heart failure, but doctors have worried about prolonged low blood sugar risk after stopping treatment. This study shows that insulin clears from the body faster than previously thought, which could reduce unnecessary monitoring time and glucose supplementation, improving clinical management of poisoned patients.","specificNumbers":"","methodology":"A consecutive case series of 10 poisoned patients treated with high-dose insulin at a clinical toxicology center. Serial insulin and C-peptide blood concentrations were measured after discontinuing high-dose insulin. Apparent elimination half-lives were calculated using non-linear regression or simplified pharmacokinetic methods.","limitations":"Very small sample size of only 10 patients limits generalizability. One patient had pre-existing diabetes, five developed acute kidney injury, and three required kidney replacement therapy — introducing heterogeneity. The case series design lacks a control group. Different poisoning agents across cases may affect insulin pharmacokinetics differently."},{"rthcId":"RPEP-15793","title":"Semaglutide and Hospitalizations in Patients With Obesity and Established Cardiovascular Disease: An Exploratory Analysis of the SELECT Randomized Clinical Trial.","authors":"Nicholls, Stephen J; Ryan, Donna H; Deanfield, John; Ferreira, Daniel; Lang, Chim C; Lincoff, A Michael; Lingvay, Ildiko; Lübker, Christopher; Terns, Paula Pérez; Rasmussen, Søren; Stensen, Signe; Weeke, Peter E; Kahn, Steven E","year":2026,"journal":"JAMA cardiology, 11(2), 156-164","doi":"10.1001/jamacardio.2025.4824","pmid":"41433034","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15794","title":"Anti-bacterial properties of hyperbranched poly (epsilon-lysine) peptides dendrons for wound dressing applications: molecular specie-specific effects.","authors":"Nicolaou, Georgina; Saberianpour, Shirin; Santin, Matteo","year":2026,"journal":"BMC microbiology, 26(1), 142","doi":"10.1186/s12866-026-04763-9","pmid":"41582195","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15795","title":"Dermatological and metabolic benefits of semaglutide in psoriasis with obesity: a 6-month prospective cohort study.","authors":"Nicolau, Joana; Nadal, Antoni; Sanchís, Pilar; Pujol, Antelm; Tamayo, María Isabel; Sfondrini, Guido; Grimalt, Mireia; García, Paula; Nadal, Cristina; Masmiquel, Lluís","year":2026,"journal":"Clinical and experimental dermatology, 51(3), 442-450","doi":"10.1093/ced/llaf473","pmid":"41137591","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15796","title":"Real-world effectiveness of oral semaglutide on body weight, composition, and metabolic parameters in patients with obesity without diabetes.","authors":"Nicolau, Joana; Dotres, Keyla; Blanco-Anesto, Jorge","year":2026,"journal":"Medicina clinica, 166(4), 107364","doi":"10.1016/j.medcli.2026.107364","pmid":"41722140","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15797","title":"Weight regain after bariatric surgery: A framework for management.","authors":"Niedbala, Christine G","year":2026,"journal":"JAAPA : official journal of the American Academy of Physician Assistants, 39(3), e1-e6","doi":"10.1097/01.JAA.0000000000000322","pmid":"41733456","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15798","title":"Dapiglutide, a dual GLP-1 and GLP-2 receptor agonist, for obesity: a randomised, double-blind, placebo-controlled parallel-group, proof-of-concept trial.","authors":"Nielsen, Casper K; Pálsson, Thorir G; Forman, Julie L; Lukacova, Michaela; Jensen, Benjamin A H; Mathiesen, David S; Englund, Anders; Gether, Ida M; Johansen, Nicklas J; Pedersen, Miriam G; Hartmann, Bolette; Holst, Jens J; Knop, Filip K; Lund, Asger B","year":2026,"journal":"EClinicalMedicine, 93, 103801","doi":"10.1016/j.eclinm.2026.103801","pmid":"41768273","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15799","title":"Glucagon-Like Peptide-1 Receptor Agonists Use Does Not Increase the Risk for Acute Pancreatitis and Is Associated With Lower Complications in Patients With Type 2 Diabetes Who Develop Acute Pancreatitis: A Multicenter Analysis.","authors":"Nieto, Luis M; Martinez, John; Narvaez, Sharon I; Ko, Donghyun; Kim, Do Han; Vega, Kenneth J; Chawla, Saurabh","year":2026,"journal":"The American journal of gastroenterology, 121(2), 424-431","doi":"10.14309/ajg.0000000000003525","pmid":"40358430","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 740,370 type 2 diabetes patients (20,459 matched pairs), GLP-1 receptor agonist users showed no increased risk of developing acute pancreatitis. When pancreatitis did occur, GLP-1 RA users had dramatically better outcomes:\n\n- Complicated pancreatitis: 68% lower risk (HR 0.32, 95% CI 0.14-0.74)\n- Parenteral nutrition needs: 72% lower (HR 0.28, 95% CI 0.09-0.83)\n- Sepsis: 29% lower (HR 0.71, 95% CI 0.59-0.84)\n- Acute kidney injury: 46% lower (HR 0.54, 95% CI 0.49-0.60)\n- Shock: 48% lower (HR 0.52, 95% CI 0.36-0.75)\n- Mechanical ventilation: 77% lower (HR 0.23, 95% CI 0.16-0.33)\n- All-cause mortality: 55% lower (HR 0.45, 95% CI 0.41-0.49)\n\nThe trend toward lower uncomplicated pancreatitis risk (HR 0.71) did not reach statistical significance (95% CI 0.49-1.01).","whyItMatters":"Pancreatitis concerns have been a persistent safety question for GLP-1 medications since their introduction. With millions of people now taking semaglutide, liraglutide, and tirzepatide for diabetes and weight loss, this large real-world study provides reassuring evidence that these drugs do not increase pancreatitis risk — and may actually be protective when pancreatitis does occur.","specificNumbers":"","methodology":"This was a retrospective cohort study using the TriNetX multicenter database. Researchers identified type 2 diabetes patients who received GLP-1 receptor agonists (semaglutide, liraglutide, dulaglutide, or tirzepatide) between January 2015 and October 2023. These were matched 1:1 with non-GLP-1 RA users using propensity matching for age, demographics, comorbidities, and medications. Known pancreatitis causes (alcohol, trauma, biliary, drug-induced, hypertriglyceridemia, post-ERCP) were excluded to reduce confounding. Cox proportional hazards models estimated hazard ratios.","limitations":"This is a retrospective observational study, which cannot establish causation. Despite propensity matching, unmeasured confounders may exist. The TriNetX database may have coding and documentation biases. The study excluded common pancreatitis causes, which improves specificity but limits generalizability. The mechanisms behind the protective effects remain unknown and require prospective studies to confirm."},{"rthcId":"RPEP-15800","title":"Selective tumor lysis by charge-alternating spherical membrane-lytic peptide bottlebrushes via redox backbone degradation and pH-gated unmasking.","authors":"Ning, Lubin; Xu, Rui; Qin, Chaoke; Sun, Lei; Shao, Liming; Zhang, Hongrui; Yan, Li; Ren, Gengzhi; Sun, Xiuying; Chang, Hao; Cheng, Xiangdong; Jia, Fie","year":2026,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 392, 114692","doi":"10.1016/j.jconrel.2026.114692","pmid":"41654124","tags":["cancer-immunotherapy","drug-delivery"],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"The Charge-Alternating Spherical MLP (CAS-MLP) platform uses a two-layer protection strategy. Structurally, membrane-lytic peptides are grafted onto a poly(disulfide) backbone in a bottlebrush architecture, which protects them from enzymatic breakdown and extends their time in circulation. Chemically, detachable charge-alternating reagents neutralize the peptides' lytic activity during transit, preventing hemolysis and off-target damage.\n\nActivation is sequential: after cancer-targeting ligands guide the nanoparticle into tumor cells, the acidic endosomal environment triggers removal of the charge-alternating shield. Then the reductive cytosol degrades the disulfide backbone, releasing individual active peptides. In vivo testing demonstrated potent tumor growth suppression with negligible side effects, solving the safety problem that has blocked membrane-lytic peptides from clinical use.","whyItMatters":"Membrane-lytic peptides are among the most potent cancer-killing agents known — they physically destroy cell membranes rather than relying on specific molecular targets, making resistance much harder to develop. But their toxicity to healthy cells has been a dealbreaker. This platform elegantly solves that problem with a dual-trigger system that only activates inside cancer cells. If it translates to human use, it could open an entirely new class of cancer therapeutics based on peptides that physically destroy tumors.","specificNumbers":"Potent tumor growth suppression in vivo; negligible side effects; dual-stimuli activation (pH + redox)","methodology":"The researchers engineered bottlebrush-shaped nanoparticles by grafting membrane-lytic peptides as side chains onto a redox-responsive poly(disulfide) backbone. They chemically masked the peptides using maleamic anhydride-amine chemistry and attached cancer-targeting ligands. The system was tested for stability, hemolysis prevention, and selective activation in cancer cell cultures, followed by efficacy and safety evaluation in tumor-bearing animal models.","limitations":"The abstract provides no specific quantitative data on tumor size reduction, survival improvement, or comparative efficacy. All data are from animal models with no human testing. The complexity of the nanoparticle engineering may present manufacturing and scalability challenges. Long-term toxicity and immunogenicity of the platform are unknown."},{"rthcId":"RPEP-15801","title":"Phase I/II clinical trial of a melanoma vaccine targeting shared non-mutated antigens and a shared mutated BRAF neoantigen with an agonistic CD40 antibody (CDX-1140) plus TLR3 agonist (poly-ICLC).","authors":"Ninmer, Emily K; Petroni, Gina R; Gastman, Brian R; Gaughan, Elizabeth M; Isaacs, James M; Haden, Kathleen; Kaur, Varinder; Wages, Nolan A; Chianese-Bullock, Kimberly A; Smith, Kelly T; Wright, Paul; Bryant, Jennifer; Dunlap-Brown, Marya; Engel, Jack A; Bekiranov, Stefan; Mauldin, Ileana S; Truong, Thach-Giao; Bullock, Timothy N J; Slingluff, Craig L","year":2026,"journal":"Journal for immunotherapy of cancer, 14(3)","doi":"10.1136/jitc-2025-013613","pmid":"41775435","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15802","title":"Exploration of Multiple Non-Invasive Tests for Assessing Response to Treatment in a Semaglutide Phase 2b Trial in Patients with MASH.","authors":"Nitze, Louise Maymann; Ratziu, Vlad; Sanyal, Arun J; Wong, Vincent Wai-Sun; Balendran, Clare; Fleckner, Jan; Skalshøi Kjær, Mette; Krarup, Niels; Anstee, Quentin M","year":2026,"journal":"Alimentary pharmacology & therapeutics, 63(3), 396-404","doi":"10.1111/apt.70376","pmid":"40985232","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15803","title":"Novel stomach-predominant C-type lectin (LvnCTL) triggers immune response against Vibrio parahaemolyticus and WSSV in shrimp Litopenaeus vannamei.","authors":"Niu, Shengwen; Fu, Ning; Wang, Yuyu; Xing, Mengxin; An, Meiling; Xu, Hongli; Xiao, Bang; Song, Weiyan; Zeng, Yongqing; Borras-Hidalgo, Orlando; Wang, Hui","year":2026,"journal":"Fish & shellfish immunology, 171, 111158","doi":"10.1016/j.fsi.2026.111158","pmid":"41619827","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15804","title":"Assessment of the Potential of GLP-1 Analogs in the Treatment of Addictions: A Literature Review.","authors":"Noemi Torres, Isabel; Barroso Alverde, Maria Jimena","year":2026,"journal":"Substance use & addiction journal, 47(1), 271-278","doi":"10.1177/29767342251351111","pmid":"40765170","tags":[],"studyType":"review","evidenceStrength":"low-moderate","keyFinding":"GLP-1 analogs have demonstrated the ability to reduce substance use in preclinical studies, decreasing alcohol and nicotine consumption in rodents and non-human primates by modifying neurotransmitter activity in brain reward pathways. These medications also showed neuroprotective effects, reducing the oxidative stress and neuroinflammation caused by chronic substance use.\n\nEarly clinical trials are beginning to show promise for translating these preclinical findings to humans, though evidence remains preliminary. The review highlights that GLP-1 analogs could address a major unmet need, given the limited success of existing pharmacotherapies for alcohol use disorder and the overall lack of effective treatments for substance use disorders.","whyItMatters":"Addiction treatment has extremely limited pharmacological options — only three drugs are approved for alcohol use disorder, and success rates are low. If GLP-1 analogs can reduce addictive behaviors through their effects on brain reward circuits, they could represent the first major new class of addiction medications in decades, repurposed from an already widely prescribed drug class.","specificNumbers":"Reviewed preclinical + early clinical studies · Reduced alcohol and nicotine use in animal models · Neuroprotective effects demonstrated · Limited existing AUD pharmacotherapy options","methodology":"Literature review searching PubMed and Cochrane databases for preclinical and early clinical studies on GLP-1 analogs and addiction, using keywords including 'GLP-1 analogs,' 'addiction,' and 'substance use disorders.'","limitations":"Most evidence is preclinical (animal studies). Early clinical trials are few and small. Long-term adverse effects of GLP-1 analogs for addiction treatment are not yet understood. The review is narrative rather than systematic, and specific study quality assessments are not described."},{"rthcId":"RPEP-15805","title":"Association Between GLP-1 Receptor Agonists and Ischemic Optic Neuropathy: A Meta-analysis.","authors":"Nogueira, Alleh; Rassi, Tiago N O; Iqbal, Asad; Felix, Nicole; Alghaith, Omar; Khan, Asad; Rassi, Nelson; Maia, Mauricio; Moura, Filipe A","year":2026,"journal":"Diabetes care","doi":"10.2337/dc25-1238","pmid":"41498755","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15806","title":"Glucagon-Like Peptide 1 Receptor Agonists and Risk of Nonarteritic Anterior Ischemic Optic Neuropathy in Patients With Type 2 Diabetes.","authors":"Noh, Yunha; Yin, Hui; Ben Ghezala, Inès; Yu, Oriana H Y; Suissa, Samy; Azoulay, Laurent","year":2026,"journal":"Diabetes care","doi":"10.2337/dc25-2577","pmid":"41701611","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"At 1 year, GLP-1 RA initiators had 18.5 NAION events per 100,000 people compared to 7.2 per 100,000 among DPP-4 inhibitor initiators. The adjusted risk ratio was 2.56 (95% CI: 1.44-4.86), with an absolute risk difference of 11.3 per 100,000.\n\nThe risk was highest during the first 6 months of use and diminished with longer treatment duration. Subgroup analyses showed higher risk in patients under 50 years old, men, ever-smokers, and those with a hemoglobin A1c reduction of 1% or more — suggesting that rapid blood sugar lowering may be a contributing factor.","whyItMatters":"GLP-1 receptor agonists are among the most widely prescribed drugs in the world, used by millions for diabetes and weight loss. NAION is a rare but serious eye condition that causes sudden, often permanent vision loss. This large-scale study raises an important safety signal that clinicians and patients should be aware of, even though the absolute risk is small.","specificNumbers":"","methodology":"This was an active-comparator, new-user cohort study that emulated a pragmatic target trial using the UK Clinical Practice Research Datalink. It compared adults with type 2 diabetes who newly started a GLP-1 RA versus a DPP-4 inhibitor. DPP-4 inhibitors were chosen as the comparator because they serve a similar clinical role but have no known association with NAION. Results were adjusted using propensity-score fine-stratification weighting to account for differences between the groups.","limitations":"As an observational study, it cannot prove that GLP-1 drugs directly cause NAION — only that there is an association. Despite propensity-score adjustment, residual confounding from unmeasured factors is possible. The absolute number of NAION events was small (14 in the GLP-1 group), which limits the precision of subgroup analyses. The study used diagnostic codes, which may miss some cases or include misdiagnoses. It also could not distinguish between specific GLP-1 RA medications."},{"rthcId":"RPEP-15807","title":"Cardiovascular complication by COVID-19 infection in SSc patients with anti-RNA polymerase III antibody.","authors":"Nomura, Megumi; Ueda-Hayakawa, Ikuko; Jikihara, Narumi; Aragane, Nobumasa; Tonomura, Kyoko; Matsumura, Yutaka; Oshima, Shiro; Kioka, Hidetaka; Akazawa, Yasuhiro; Sakata, Yasushi; Fujimoto, Manabu","year":2026,"journal":"Rheumatology (Oxford, England), 65(2)","doi":"10.1093/rheumatology/keaf605","pmid":"41237310","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15808","title":"Systemic Pharmacokinetic Principles of Therapeutic Peptides.","authors":"Nordell, Pär; Jansson-Löfmark, Rasmus; Gennemark, Peter","year":2026,"journal":"Clinical pharmacokinetics","doi":"10.1007/s40262-025-01615-z","pmid":"41661442","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15809","title":"Immunomodulatory effects of cathelicidin in the gut-brain axis: A novel link between mucosal immunity and neuroinflammation.","authors":"Nourizadeh, Mehrdad; Ghahari, Amir Arsalan; Zandi, Ehsan; Rasouli, Seyedeh Zeynab; Davari, Shaghayegh; Hoseinzadeh, Mobina; Nourazar, Mir Alireza","year":2026,"journal":"Experimental physiology","doi":"10.1113/EP093221","pmid":"41493387","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review synthesizes evidence that cathelicidin peptides serve multiple roles in gut-brain communication. In the gut, cathelicidin maintains intestinal barrier integrity, shapes microbiota composition, and regulates innate immune signaling. Gut-derived metabolites including short-chain fatty acids and vitamin D influence cathelicidin expression, creating feedback loops between diet, microbiome, and mucosal defense.\n\nIn the CNS, cathelicidin shows a striking functional dichotomy: when produced by neurons, it acts as a neuroprotective modulator, but when delivered by peripheral immune cells infiltrating the brain, it exacerbates glial-mediated inflammation. This context-dependent behavior — where the same peptide can protect or harm depending on its source and local environment — is a key insight for understanding neuroinflammatory disease mechanisms.","whyItMatters":"The gut-brain axis is increasingly recognized as central to neuroinflammatory and neurodegenerative diseases. Finding that a single peptide — LL-37 — can act as both a local effector in the gut and a systemic messenger reaching the brain fundamentally changes how we think about antimicrobial peptides. It suggests that gut health interventions (probiotics, vitamin D, dietary changes that boost cathelicidin) could influence brain inflammation, and that cathelicidin itself could be a therapeutic target or diagnostic biomarker for gut-brain axis disorders.","specificNumbers":"","methodology":"Narrative review synthesizing animal and human research on cathelicidin biology in the gastrointestinal and central nervous systems, with focus on the gut-brain axis communication pathways.","limitations":"As a review, this synthesizes existing literature rather than presenting new data. Much of the mechanistic evidence comes from animal models (primarily rodent CRAMP studies), and the human relevance of all findings is not confirmed. The context-dependent effects of cathelicidin are complex and not fully characterized. The review proposes cathelicidin as a gut-brain mediator, but direct causal evidence for this communication pathway in human neuroinflammatory disease is limited."},{"rthcId":"RPEP-15810","title":"Insulin therapy DE-intensificAtion with iGlarLixi: A phase 4, open-label, parallel-group randomised controlled trial.","authors":"Novodvorský, Peter; Thieme, Lenka; Laňková, Ivana; Franková, Štěpánka; Veselá, Alica; Záhumenský, Emil; Edelsberger, Tomáš; Löblová, Marie; Žižka, Ondřej; Vytasil, Miroslav; Lauand, Felipe; Bonnemaire, Mireille; Hrubý, Filip; Mráz, Miloš; Haluzík, Martin","year":2026,"journal":"Diabetes, obesity & metabolism, 28(3), 1817-1825","doi":"10.1111/dom.70362","pmid":"41395661","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15811","title":"Trajectories of Biomarkers Before and After Hospitalization for Heart Failure in Patients With Heart Failure.","authors":"Nozaki, Asuka; Kondo, Toru; Nagai, Shin; Imaizumi, Takahiro; Mizuno, Chiaki; Komeyama, Shotaro; Ito, Ryota; Kazama, Shingo; Hiraiwa, Hiroaki; Morimoto, Ryota; Murohara, Toyoaki","year":2026,"journal":"Circulation journal : official journal of the Japanese Circulation Society, 90(2), 185-192","doi":"10.1253/circj.CJ-25-0824","pmid":"41443825","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15812","title":"Predicting peptide orientation in membrane interactions: a review on transmembrane and surface-bound states.","authors":"Nunes, Lúcio Otávio","year":2026,"journal":"European biophysics journal : EBJ, 55(1), 9-20","doi":"10.1007/s00249-025-01810-7","pmid":"41575497","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15813","title":"Glucagon-like peptide-1 receptor agonists: a review of the literature from a dental perspective.","authors":"O Driscoll, Jill; McIntyre, Grant","year":2026,"journal":"British dental journal, 240(3), 144-148","doi":"10.1038/s41415-025-9345-4","pmid":"41688699","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15814","title":"GLP-1 receptor agonists in asthma: targeting metabolic-inflammatory crossroads.","authors":"O'Brien, Helen; Franciosi, Alessandro N; Butler, Marcus W","year":2026,"journal":"Current opinion in pulmonary medicine","doi":"10.1097/MCP.0000000000001249","pmid":"41664500","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15815","title":"Glucagon-like-peptide-1 and Mental Health: The Unexpected Outcomes.","authors":"O'Connor, Melody A; Peters, Angela; Reddin, Christopher J","year":2026,"journal":"The Nursing clinics of North America, 61(1), 91-100","doi":"10.1016/j.cnur.2025.09.005","pmid":"41581971","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15816","title":"Navigating the benefits and harms of GLP-1 and GLP-1/GIP agonists in obesity.","authors":"O'Connor, Raymond","year":2026,"journal":"Drug and therapeutics bulletin, 64(2), 19-23","doi":"10.1136/dtb.2025.000039","pmid":"41513440","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15817","title":"The effect of GLP-1 receptor agonists on cognition in nondiabetic patients with mild cognitive impairment or alzheimer's disease: a meta-analysis of randomized controlled trials.","authors":"O'Mara, Ashley; Mody, Bhakti Pradip; Mammi, Marco; Simjian, Thomas; Ghattas, Kyrellos; Kaliki, Srilekha; Le, Ngoc Phuong Mai; Liew, Aaron; Migliore, Mattia; Mekary, Rania A","year":2026,"journal":"Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 47(1), 149","doi":"10.1007/s10072-025-08602-z","pmid":"41524953","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15818","title":"Innervation Changes in Apical Periodontitis and its Correlation with Preoperative Symptoms.","authors":"Obadah, Austah; Fu, Johnathan; Wong, David; Diogenes, Anibal","year":2026,"journal":"Journal of endodontics, 52(1), 62-67","doi":"10.1016/j.joen.2025.07.018","pmid":"40774582","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15819","title":"Exploring the theranostic potential of two metabolically stable GRPR-targeting peptides labelled with Ga-68 for PET imaging.","authors":"Obeid, Karim; Bezverkhniaia, Ekaterina; Tolmachev, Vladimir; Orlova, Anna; Kanellopoulos, Panagiotis","year":2026,"journal":"EJNMMI radiopharmacy and chemistry, 11(1)","doi":"10.1186/s41181-026-00431-5","pmid":"41701408","tags":[],"studyType":"animal","evidenceStrength":"preliminary","keyFinding":"Two metabolically stable peptides targeting the gastrin-releasing peptide receptor (GRPR) — [68Ga]Ga-PKB2 and [68Ga]Ga-PKB3 — were successfully labeled with gallium-68 for PET imaging. Both showed high tumor uptake in prostate cancer xenografts (16 ± 3%IA/g and 17 ± 2%IA/g, respectively), fast blood clearance below 0.5%IA/g at 2 hours, and low nanomolar receptor affinity.\n\n[68Ga]Ga-PKB3 showed significantly higher uptake in GRPR-expressing pancreas tissue and lower kidney uptake than PKB2, suggesting a potentially better safety profile. PET/CT images clearly delineated tumors, and both tracers are proposed as diagnostic counterparts to their lutetium-177-labeled therapy versions, forming a theranostic pair.","whyItMatters":"GRPR is overexpressed in several cancers including prostate, breast, and pancreatic cancer. Having matched diagnostic and therapeutic peptide pairs — one for imaging with PET, one for targeted radiation therapy — could let doctors first locate tumors precisely and then treat them with the same targeting molecule. This study advances the concept of peptide-based theranostics where the same receptor-binding peptide serves both diagnostic and therapeutic purposes.","specificNumbers":"n=PC-3 xenograft mice · Tumor uptake: 16 ± 3%IA/g (PKB2), 17 ± 2%IA/g (PKB3) · IC50: low nanomolar · Radiochemical yield >99% · Radiochemical purity >97% · Blood clearance <0.5%IA/g at 2h","methodology":"Researchers labeled two previously developed GRPR-targeting peptides (PKB2 with DOTAGA chelator, PKB3 with DOTA chelator) with gallium-68. They tested receptor affinity and cell uptake in PC-3 prostate cancer cells, then evaluated biodistribution and PET/CT imaging in mice bearing PC-3 tumor xenografts.","limitations":"This is a preclinical animal study only — no human data exists yet. The mouse xenograft model may not perfectly reflect how these tracers behave in human tumors. Long-term toxicity and repeated dosing were not assessed. Translation to clinical use will require Phase I safety trials."},{"rthcId":"RPEP-15820","title":"Beyond glycemic control: Sex differences shaping glucagon-like peptide-1 receptor agonist utilization in the United States.","authors":"Ofili, Samuel C; Chen, Hua","year":2026,"journal":"Journal of managed care & specialty pharmacy, 32(2), 166-175","doi":"10.18553/jmcp.2026.32.2.166","pmid":"41636679","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15821","title":"Liraglutide alters gut microbiota and improves endothelium-dependent relaxation in db/db mice.","authors":"Oh, Eun Yi; Suh, Soo Hwan; Byeon, Seonhee; Lee, Jooyong; Lee, Young-Ho; Choi, Soo-Kyoung","year":2026,"journal":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 196, 119042","doi":"10.1016/j.biopha.2026.119042","pmid":"41633255","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In db/db diabetic mice treated with liraglutide (300 μg/kg/day IP for 2 weeks):\n\n- **Vascular function**: Endothelium-dependent relaxation was significantly improved in mesenteric resistance arteries.\n- **Endothelial signaling**: In high-glucose-treated HUVECs, liraglutide restored eNOS phosphorylation (at Ser1177) and nitric oxide production.\n- **Gut microbiome**: Diabetes caused marked dysbiosis with reduced alpha diversity and depletion of short-chain fatty acid (SCFA)-producing taxa. Liraglutide substantially restored microbial diversity and enriched beneficial genera including Lachnospiraceae and Lactobacillus.\n- **Butyrate connection**: Low-dose butyrate independently enhanced nitric oxide production in endothelial cells, supporting a causal link between microbiome changes and vascular improvement.","whyItMatters":"Cardiovascular disease is the leading cause of death in diabetes, and endothelial dysfunction is where it starts. This study reveals a novel mechanism by which GLP-1 drugs protect the heart: by reshaping gut bacteria to produce more butyrate, which helps blood vessels make nitric oxide. This 'drug-microbiome-vessel axis' could explain why GLP-1 agonists have such strong cardiovascular benefits in clinical trials — and could inspire microbiome-targeted add-on therapies.","specificNumbers":"","methodology":"Male db/db mice (a genetic diabetes model) and non-diabetic controls received liraglutide (300 μg/kg/day IP) or saline for 2 weeks. Vascular function was measured in mesenteric resistance arteries using wire myography. Endothelial nitric oxide signaling was assessed in HUVECs (human umbilical vein endothelial cells) exposed to high glucose ± liraglutide or butyrate. Gut microbiota composition was analyzed by 16S rRNA gene sequencing.","limitations":"The study used intraperitoneal (not subcutaneous) liraglutide administration, which may produce different pharmacokinetics than the clinical route. The 2-week treatment duration is short relative to chronic human use. The butyrate-NO connection was demonstrated in cell culture only, not confirmed as the in vivo mediating mechanism. Gut microbiome changes are correlational — a fecal transplant experiment would be needed to prove causation."},{"rthcId":"RPEP-15822","title":"Staphylococcus capitis strain producing dual bacteriocins, capidermicin and micrococcin P1, shows broad-spectrum antimicrobial activity.","authors":"Ohdan, Keijuro; Suzuki, Yujin; Kawada-Matsuo, Miki; Hara, Toshinori; Nguyen-Tra Le, Mi; Segawa, Takaya; Hisatsune, Junzo; Sugawara, Yo; Kashiyama, Seiya; Ohge, Hiroki; Sugai, Motoyuki; Aikawa, Tomonao; Komatsuzawa, Hitoshi","year":2026,"journal":"Scientific reports, 16(1), 6835","doi":"10.1038/s41598-026-36393-6","pmid":"41620502","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15823","title":"A phase 1 single and multiple ascending dose study of orforglipron in Japanese participants with type 2 diabetes.","authors":"Ohwaki, Kenji; Nakamura, Chino; Nasu, Risa; Takenouchi, Kazumasa; Hirase, Tetsuaki","year":2026,"journal":"Journal of diabetes investigation, 17(2), 205-213","doi":"10.1111/jdi.70157","pmid":"41325139","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15824","title":"Association between incretin-related drugs and fractures in patients treated with pioglitazone: A pharmacovigilance study using the FDA Adverse Event Reporting System.","authors":"Ohyama, Katsuhiro; Abe, Nonoka; Okamoto, Takumi; Hori, Yusuke","year":2026,"journal":"International journal of clinical pharmacology and therapeutics, 64(1), 1-8","doi":"10.5414/CP204789","pmid":"41122011","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15825","title":"Insulin edema in slowly progressive type 1 diabetes: improvement following adjustment of insulin therapy.","authors":"Okamura, Emi; Harada, Norio; Okuno, Kana; Yamamoto, Kana; Murakami, Takaaki; Ueda, Yohei; Yabe, Daisuke","year":2026,"journal":"Diabetology international, 17(1), 13","doi":"10.1007/s13340-025-00864-4","pmid":"41476905","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A patient with slowly progressive type 1 diabetes mellitus (SPIDDM) developed bilateral lower-leg edema and approximately 7 kg of weight gain shortly after starting basal-bolus insulin therapy with insulin aspart and insulin degludec. Cardiac function was normal on echocardiography and B-type natriuretic peptide levels were within the reference range, ruling out heart failure.\n\nThe edema resolved rapidly within nine days following modification of the insulin regimen and dietary sodium restriction to 8 g/day of salt, without requiring diuretics. The improvement likely reflected the combined effects of glycemic stabilization, fluid-electrolyte balance, and possible formulation-related factors rather than a direct difference between insulin types.","whyItMatters":"Insulin edema is rare and often unrecognized, which can lead to unnecessary diagnostic workups or inappropriate treatment. This case demonstrates that even patients with slowly progressive type 1 diabetes — not just those with new-onset or poorly controlled disease — can develop this complication. Recognizing insulin edema early allows clinicians to manage it conservatively through regimen adjustment and salt restriction rather than resorting to diuretics or discontinuing essential insulin therapy.","specificNumbers":"","methodology":"This is a clinical case report of a single patient. The patient was evaluated with echocardiography and B-type natriuretic peptide testing to exclude cardiac causes. Management involved adjusting the insulin regimen (from insulin aspart and insulin degludec) and implementing dietary sodium restriction. The clinical course was documented over the treatment period.","limitations":"As a single case report, this provides no data on incidence, prevalence, or generalizable treatment outcomes. The mechanism of improvement could not be definitively attributed to insulin regimen adjustment versus sodium restriction versus natural resolution. The historical incidence figure (3.5%) comes from a single older study from Africa and may not be generalizable. No controlled comparison of insulin formulations was possible."},{"rthcId":"RPEP-15826","title":"Glucagon-like peptide-1 receptor agonists and reduced mortality, cardiovascular and psychiatric risks in patients with psoriasis: a large-scale cohort study.","authors":"Olbrich, Henning; Kridin, Khalaf; Zirpel, Henner; Hernandez, Gema; Sadik, Christian D; Gaffal, Evelyn; Thaçi, Diamant; Ludwig, Ralf J","year":2026,"journal":"The British journal of dermatology, 194(1), 59-66","doi":"10.1093/bjd/ljaf346","pmid":"40897378","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15827","title":"In Silico Identification of Antiviral Peptides as Potential Leads Against Sudan Ebolavirus VP-40.","authors":"Omara, Boniface; Kiyimba, Kenedy; Fofana, Fatoumata G; Diabaté, Oudou; Odur, Walter; Jjingo, Daudi; Iramiot, Jacob Stanley; Draleru, Peace; Achia, Joan; Shafiq, Muhammad; Ul-Haq, Zaheer; Okella, Hedmon; Odongo, Steven","year":2026,"journal":"BioMed research international, 2026, 2204127","doi":"10.1155/bmri/2204127","pmid":"41608076","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15828","title":"Retrospective comparison of the clinical effects of oral semaglutide and SGLT2 inhibitors treatment in patients with type 2 diabetes.","authors":"Omori, Yasuhiro; Usui, Ryota; Yamazaki, Yuji; Kuwata, Hitoshi; Hamamoto, Yoshiyuki; Yamada, Yuichiro; Seino, Yutaka","year":2026,"journal":"Journal of diabetes investigation, 17(3), 432-438","doi":"10.1111/jdi.70240","pmid":"41555812","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15829","title":"Neuron-specific overexpression of human vasoactive intestinal peptide receptor 2 in mice causes cognitive dysfunction and abnormal dendritic morphology in the prefrontal cortex.","authors":"Ono, Ami; Miyaoka, Tatsunori; Koan, Daichi; Jin, Zihao; Chen, Lu; Hayata-Takano, Atsuko; Asano, Satoshi; Yokoyama, Rei; Ishimoto, Kenji; Hino, Nobumasa; Harada, Akihiro; Nakazawa, Takanobu; Hashimoto, Hitoshi; Waschek, James A; Nakagawa, Shinsaku; Tanimoto, Kotaro; Ago, Yukio","year":2026,"journal":"Journal of pharmacological sciences, 160(2), 111-121","doi":"10.1016/j.jphs.2025.12.005","pmid":"41554595","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15830","title":"Do GLP-1 agonists affect perioperative risk in spine surgery? A systematic review and meta-analysis.","authors":"Ononogbu-Uche, Favour C; Toussaint, Felix; Saleh, Abdullah W; Siddig, Afnan Hassab E; Ahmed, Ramzy; Akl, Karim; Algabri, Mostafa H; Alwadai, Mohamed; Corliss, Lauren; Foster, Norah; Abd-El-Barr, Muhammad M","year":2026,"journal":"North American Spine Society journal, 25, 100835","doi":"10.1016/j.xnsj.2025.100835","pmid":"41551027","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15831","title":"Effects of Treatment with Glucagon-like Peptide-1 Receptor Analogues on the Diabetic Foot.","authors":"Ortiz Romero, Mercedes; Rodríguez de Vera Gómez, David; Rodríguez de Vera Gómez, Pablo; Gordillo Fernández, Luis María","year":2026,"journal":"Biomedicines, 14(2)","doi":"10.3390/biomedicines14020406","pmid":"41751305","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15832","title":"Apelin-13 confers Neuropeptide Y-mediated neuroprotection and preserves learning and allocentric memory in D-glutamic acid-induced excitotoxicity in rats.","authors":"Oruc, Kadriye Yagmur; Oruc, Aykut; Arslan, Ruhat; Diriarin, Furkan Pasa; Mengi, Murat; Tanriverdi, Gamze; Yanar, Karolin; Ozeren Eser, Mediha; Agturk, Gokhan; Sonkurt, Ali Ihsan; Guler, Berkay; Seymen, Hakki Oktay","year":2026,"journal":"Molecular neurobiology, 63(1), 387","doi":"10.1007/s12035-026-05685-3","pmid":"41571878","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15833","title":"Mental health outcomes in obesity interventions with GLP-1 receptor agonists: is it similar to other obesity interventions? A narrative review with systematic evidence synthesis.","authors":"Osborne, Darin; Abdelgadir, Elamin","year":2026,"journal":"International journal of obesity (2005)","doi":"10.1038/s41366-025-02002-1","pmid":"41491273","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 receptor agonists (semaglutide, liraglutide, tirzepatide) showed improvement in patient-reported mental wellbeing across several clinical trials. Initial pharmacovigilance data raised concern about a possible association with suicidality, but subsequent robust cohort studies and meta-analyses have refuted this association.\n\nCompared to other obesity interventions: behavioral interventions showed no harm and modest mental health benefits; bariatric surgery improved depression and anxiety short-to-medium-term but some studies reported increased suicidality after 5 years; other pharmacotherapies (orlistat, bupropion/naltrexone, phentermine/topiramate) showed mixed psychiatric impacts. Overall, most weight loss interventions appear psychologically safe or beneficial.","whyItMatters":"The suicidality concerns around GLP-1 drugs generated significant media attention and regulatory scrutiny, potentially discouraging patients from beneficial treatment. This review provides an evidence-based answer: the suicide signal was not confirmed by rigorous studies. More importantly, it highlights that mental health is an underprioritized element of obesity management across all treatment modalities — and that GLP-1 drugs may actually be among the safer options from a psychiatric perspective.","specificNumbers":"","methodology":"Narrative review with systematic evidence synthesis. Literature search across MEDLINE, Embase, and Cochrane databases, focusing on meta-analyses, systematic reviews, and clinical trials published through June 2025. Mental health outcomes examined included quality of life, anxiety, depression, and suicidality across lifestyle, pharmacological, and surgical obesity interventions.","limitations":"This is a narrative review, not a formal systematic review or meta-analysis, which may introduce selection bias. Long-term mental health data for GLP-1 agonists are still limited compared to the decades of follow-up available for bariatric surgery. The improvement in mental wellbeing could be secondary to weight loss and improved physical health rather than a direct drug effect. Pharmacovigilance databases are subject to reporting bias. Patients with significant psychiatric history were often excluded from clinical trials."},{"rthcId":"RPEP-15834","title":"Characterization of jejunal enteroids in human obesity; a model for studying GLP-1 cells.","authors":"Osinski, Céline; Martinez-Oca, Paula; Moret, Dounia; Genser, Laurent; Poitou, Christine; Soula, Hédi Antoine; Clément, Karine; Serradas, Patricia; Ribeiro, Agnès","year":2026,"journal":"International journal of obesity (2005)","doi":"10.1038/s41366-026-02024-3","pmid":"41663679","tags":[],"studyType":"human-cells","evidenceStrength":"preliminary","keyFinding":"Researchers successfully grew miniature intestine models (enteroids) from jejunum tissue taken during gastric bypass surgery in people with severe obesity. These enteroids contained functional GLP-1-producing cells and secreted active GLP-1 in response to glucose.\n\nCritically, enteroids from patients with both obesity and type 2 diabetes had a reduced ability to release GLP-1 when exposed to high glucose, compared to enteroids from obese patients without diabetes or with prediabetes. This confirms that the impaired GLP-1 response seen in T2D is an intrinsic defect in the gut's hormone-producing cells, not just a secondary effect of the disease.","whyItMatters":"Understanding why GLP-1 secretion is impaired in type 2 diabetes is fundamental to improving treatments. This study creates a human-derived lab model that lets researchers study GLP-1 cells directly from patients with metabolic disease — something previously very difficult because these hormone-producing cells are extremely rare in the gut lining. This tool could accelerate development of therapies that restore natural GLP-1 production rather than relying on injected drugs.","specificNumbers":"n=34 total · Ob (obesity only): n=12 · ObPreD (obesity + prediabetes): n=12 · ObD (obesity + T2D): n=10 · Tissue source: jejunum during gastric bypass · T2D group: reduced GLP-1 secretion at high glucose","methodology":"Generated human jejunal enteroids from jejunum fragments collected during gastric bypass surgery across three groups: severe obesity with normal blood sugar (n=12), with prediabetes (n=12), and with type 2 diabetes (n=10). Characterized enteroids using gene/protein expression and immunofluorescence. Used Notch pathway inhibitor DAPT to promote enteroendocrine cell differentiation. Measured active GLP-1 secretion by ELISA at low and high glucose concentrations.","limitations":"All tissue samples came from patients with severe obesity undergoing bariatric surgery, so findings may not apply to non-obese individuals or those with milder obesity. Enteroids are simplified models that lack the neural, immune, and vascular components of living intestine. The sample size (10-12 per group) is relatively small. In vitro GLP-1 secretion may not perfectly reflect in vivo gut hormone dynamics."},{"rthcId":"RPEP-15835","title":"Synthesis and evaluation of 14β-acyl substituted 17-cyclopropylmethyl-7,8-dihydromorphinone derivatives: mixed partial agonists at mu opioid and nociception/orphanin FQ peptide receptors.","authors":"Ostovar, Mehrnoosh; Olsen, Keith; Cami-Kobeci, Gerta; Traynor, John R; Jeramaz, Luka; Kirton, Stewart B; Husbands, Stephen M","year":2026,"journal":"RSC medicinal chemistry","doi":"10.1039/d5md00685f","pmid":"41777555","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15836","title":"Comparative Effectiveness of Tirzepatide Versus Dulaglutide or Semaglutide on Major Cardiovascular Events in Type 2 Diabetes and Cardiovascular Disease: Insights From Two Target-Trial Emulations.","authors":"Ostrominski, John W; Ortega-Montiel, Janinne; Wexler, Deborah J; Everett, Brendan M; Cromer, Sara J; Byrne, Caroline F; Glynn, Robert J; Paik, Julie M; Patorno, Elisabetta","year":2026,"journal":"Diabetes care","doi":"10.2337/dc25-3063","pmid":"41778928","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"After propensity score matching: Tirzepatide vs. dulaglutide (9,233 pairs) — tirzepatide had lower modified MACE (IR 31.3 vs 39.4 per 1,000 person-years; HR 0.80, 95% CI 0.65-0.99), driven by 40% lower all-cause mortality (HR 0.60, 95% CI 0.43-0.83). Post hoc analysis showed lower pneumonia hospitalization with tirzepatide vs dulaglutide. Tirzepatide vs. semaglutide (25,266 pairs) — modified MACE rates were similar (IR 23.7 vs 23.2; HR 1.03, 95% CI 0.90-1.17).","whyItMatters":"This is the largest real-world head-to-head comparison of tirzepatide against both dulaglutide and semaglutide for cardiovascular outcomes. It provides immediate clinical guidance: tirzepatide is clearly superior to dulaglutide for heart protection and equivalent to semaglutide. For patients currently on dulaglutide, switching to tirzepatide may reduce cardiovascular risk. For those choosing between tirzepatide and semaglutide, cardiovascular protection appears similar.","specificNumbers":"","methodology":"Two target trial emulations using commercially insured US adults (June 2022-December 2024) with type 2 diabetes and established atherosclerotic cardiovascular disease. New initiators of tirzepatide were propensity score matched 1:1 with dulaglutide initiators (9,233 pairs) and separately with semaglutide initiators (25,266 pairs). Primary outcome was modified MACE (composite of non-fatal MI, non-fatal stroke, and all-cause death). Incidence rates and hazard ratios were estimated.","limitations":"Observational target trial emulation — despite propensity score matching, unmeasured confounding cannot be excluded. The study used insurance claims data, which may have coding inaccuracies. The relatively short follow-up period (up to ~2.5 years) may not capture long-term differences. Tirzepatide initiators may differ from dulaglutide/semaglutide initiators in unmeasurable ways (e.g., provider enthusiasm, patient motivation). The pneumonia finding was post hoc and hypothesis-generating. Commercially insured patients may not represent Medicare or uninsured populations."},{"rthcId":"RPEP-15837","title":"Development of a Peptide-Based Photoimmunotherapy Drug Targeting PD-L1.","authors":"Otani, Takuya; Kondo, Naoya; Kanai, Ayaka; Hanaoka, Hirofumi","year":2026,"journal":"Molecules (Basel, Switzerland), 31(2)","doi":"10.3390/molecules31020302","pmid":"41599351","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The WL12 peptide conjugated with the photoabsorber IR700 (WL12-IR700) successfully induced cancer cell death when activated by near-infrared light. Cell killing was both light dose-dependent and drug concentration-dependent, confirming the dual-trigger mechanism. In PD-L1-positive cell cultures, NIR-PIT with WL12-IR700 caused characteristic morphological changes associated with photoimmunotherapy-mediated cell death. In mouse xenograft models, the treatment significantly suppressed tumor growth and extended overall survival compared to controls.","whyItMatters":"Current photoimmunotherapy uses antibody-based drugs, which are expensive and slow to develop. Peptides are much smaller, cheaper to produce, and faster to develop. This study shows a peptide can serve the same targeting role as an antibody in photoimmunotherapy, potentially making this promising cancer treatment more accessible and enabling targeting of additional cancer markers.","specificNumbers":"","methodology":"Researchers conjugated the PD-L1-binding peptide WL12 with the photoabsorber IRDye700DX (IR700). In vitro evaluation used PD-L1-positive cancer cell lines to assess cell viability and morphological changes after NIR light exposure. In vivo experiments used xenograft mouse models to measure tumor growth suppression and overall survival after treatment with WL12-IR700 combined with near-infrared light irradiation.","limitations":"This is early-stage preclinical research using cell lines and mouse xenograft models. The specific tumor suppression percentages and survival data were not detailed in the abstract. Near-infrared light has limited tissue penetration, restricting this approach to surface-accessible tumors without specialized light delivery. No toxicity or pharmacokinetic data were reported. Clinical translation would require extensive safety testing."},{"rthcId":"RPEP-15838","title":"Discovery and classification of new reptile cathelicidins by genome mining: study of their structure and genomic organization in Testudines and Squamata.","authors":"Otazo-Pérez, Andrea; López, Manuel R; González-Acosta, Sergio; Morales-delaNuez, Antonio; Pérez de la Lastra, José Manuel","year":2026,"journal":"Developmental and comparative immunology, 176, 105560","doi":"10.1016/j.dci.2026.105560","pmid":"41628674","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15839","title":"Thymosin β4-derived peptides alleviate neuroinflammation and neurite atrophy in both in vitro models and in vivo 5 × FAD mice: A potential therapy for memory improvement in Alzheimer's disease.","authors":"Ou, Haiyan; Chen, Ruiye; Zhou, Longjian; Zhang, Yi; Zhao, Shuai; Yang, Zhiyou","year":2026,"journal":"International immunopharmacology, 170, 116097","doi":"10.1016/j.intimp.2025.116097","pmid":"41443105","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15840","title":"Causal association between glucagon-like peptide-1 receptor agonists and mental disorders: insight from genetic and real-world evidence.","authors":"Ouyang, Chenhao; Zhang, Xiaoyue; Zhang, Minghai; Miao, Yan; Zhu, Zicheng; Zeng, Yunting; Ban, Hong; Wu, Yuting; Peng, Nanqin; Ling, Jitao; Li, Chen; Zhang, Deju; Yu, Peng; Zhang, Jing; Liu, Xiao; Huang, Tongsheng","year":2026,"journal":"Journal of affective disorders, 403, 121452","doi":"10.1016/j.jad.2026.121452","pmid":"41713610","tags":["glp-1-agonists","mental-health"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"Using both genetic analysis (Mendelian randomization) and a meta-analysis of clinical studies, researchers found no causal link between GLP-1 receptor activation and seven mental disorders: anxiety, bipolar disorder, chronic depression, depression, eating disorders, suicide, and schizophrenia. All genetic odds ratios were non-significant after correction.\n\nThe meta-analysis of real-world clinical data confirmed these findings, showing no significant differences between GLP-1RA users and controls for suicidal ideation/behavior (OR=0.92, p=0.67), anxiety (OR=1.03, p=0.93), or depressive symptoms (SMD=-0.25, p=0.39). However, one notable exception emerged: GLP-1RA users showed significantly reduced eating disorder symptoms (SMD=-0.71, p=0.006).","whyItMatters":"As millions of people take GLP-1 receptor agonists like semaglutide and liraglutide for diabetes and weight loss, concerns about potential psychiatric side effects — particularly suicidal thoughts and depression — have generated significant public attention and regulatory scrutiny. This study provides robust reassurance from two independent lines of evidence (genetic and clinical) that GLP-1 receptor activation does not cause mental health disorders. The finding that eating disorder symptoms actually decreased in GLP-1RA users is a positive bonus.","specificNumbers":"7 mental disorders tested · anxiety OR=0.870 · depression OR=0.985 · suicide OR=1.040 · all PFDR>0.25 (non-significant) · suicidal ideation meta-analysis OR=0.92, p=0.67 · eating disorders SMD=-0.71, p=0.006 (significant improvement)","methodology":"The researchers employed a multi-method approach: (1) Two-sample Mendelian randomization using genetic variants as instruments to assess causal relationships between GLP-1R and mental disorders, (2) Linkage Disequilibrium Score Regression (LDSC) to evaluate genetic correlations, (3) Bayesian co-localization to validate shared genetic architecture, and (4) a meta-analysis of published clinical studies comparing GLP-1RA users to controls on mental health outcomes. Results were validated using independent datasets (eQTLGen Consortium and Psychiatric Genomics Consortium).","limitations":"Mendelian randomization tests the effect of lifelong genetic variation in GLP-1R, which may differ from the effect of short-term drug exposure. The meta-analysis depends on the quality and reporting of included clinical studies. Some mental health outcomes may be underreported in clinical trials focused on metabolic endpoints. The eating disorders finding, while significant, had only a small number of studies and warrants further investigation. The study examined GLP-1RAs as a class rather than individual drugs."},{"rthcId":"RPEP-15841","title":"Mechanistic insights into psoriasis and type 2 diabetes mellitus comorbidity - Implications for treatment: A review.","authors":"Ouyang, Ling; Li, Zhanzong; Zeng, Yunhong","year":2026,"journal":"Biomolecules & biomedicine","doi":"10.17305/bb.2026.13484","pmid":"41564383","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15842","title":"Pseudomonas aeruginosa Peptide From Strain P3 (PAP3) and AKT Serine/Threonine Kinase 1 (AKT1) siRNA-Loaded Chitosan Nanoparticle as a Co-Delivery System for Enhanced Anticancer Activity in Lung Cancer Cells.","authors":"Padariyakam, Shabeer; Nair, Nimisha R; Kothari, Shanker Lal","year":2026,"journal":"Biotechnology and applied biochemistry","doi":"10.1002/bab.70123","pmid":"41549563","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15843","title":"Advances in Cardiovascular Pharmacotherapy. VI. Sacubitril-Valsartan, An Angiotensin Receptor-Neprilysin Inhibitor.","authors":"Pagel, Paul S; Hang, Dustin; Freed, Julie K; Crystal, George J","year":2026,"journal":"Journal of cardiothoracic and vascular anesthesia, 40(3), 960-984","doi":"10.1053/j.jvca.2025.12.003","pmid":"41539898","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15844","title":"Brain peptides in Alzheimer's disease - pathophysiology and therapeutic advances.","authors":"Pahal, Sonu; Gupta, Arushi; Kumar, Vivek; Singh, Prashant; Kaushik, Monu; Pahal, Vishvender; Atluri, Geethika; Chaudhary, Amit","year":2026,"journal":"Cell and tissue research, 403(3)","doi":"10.1007/s00441-026-04055-8","pmid":"41772129","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies peptides' central role in AD at both pathological and therapeutic levels: Pathogenic peptides (Aβ oligomers, hyperphosphorylated tau fragments) drive synaptic failure, mitochondrial dysfunction, and neuroinflammation. Endogenous neuropeptides provide compensatory neuroprotective, trophic, and homeostatic effects. Therapeutic advances include aggregation inhibitors, receptor-selective neuropeptide analogues, cell-penetrating peptide conjugates, and approaches targeting proteostasis, insulin/incretin signaling, neurotrophic support, and microglial activation. Critical barriers include blood-brain barrier penetration, metabolic stability, off-target effects, and need for biomarker-guided patient stratification.","whyItMatters":"Alzheimer's disease affects over 55 million people worldwide with limited treatment options. The recognition that peptides are both central to disease pathology and offer unique therapeutic advantages (high specificity, natural brain signaling) positions peptide-based approaches as a promising frontier. The inclusion of incretin/GLP-1 signaling as a therapeutic target also connects to the broader GLP-1 drug revolution.","specificNumbers":"","methodology":"Comprehensive narrative review integrating evidence on brain peptides in AD pathophysiology, peptide-based therapeutic strategies, and delivery platform advances.","limitations":"As a narrative review, this paper provides a broad overview without systematic methodology or quantitative analysis. The field is rapidly evolving, and some discussed therapeutic approaches are at very early stages with limited clinical validation. The challenge of translating peptide therapeutics across the blood-brain barrier remains a fundamental barrier that no review can fully resolve."},{"rthcId":"RPEP-15845","title":"Comprehensive assessment of erenumab efficacy in participants with high-frequency episodic migraine with at least one previously failed preventive treatment: The EMBRACE study.","authors":"Paiva da Silva Lima, Gabriel; Rao, Renata; Szabó, Gyöngyi; Szklener, Sebastian; Tassorelli, Cristina; Nastaj, Marcin; Chou, Denise E; Khodavirdi, Ani C; Chehrenama, Mahan; Zhu, Yineng; Bhatia, Ajay K; Dodick, David W","year":2026,"journal":"Headache, 66(3), 658-671","doi":"10.1111/head.15071","pmid":"41084999","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 512 randomized patients (erenumab 140 mg n=254, placebo n=256) over 3 months:\n\n- Primary endpoint: Monthly hours of moderate-severe headache pain reduced by 7.95 hours vs. placebo (95% CI: -11.45 to -4.46, p<0.001)\n- Functional impact (MFIQ): All four domains significantly improved vs. placebo (all p<0.001): physical functioning (-7.36), usual activities (-7.10), social functioning (-6.82), emotional functioning (-7.05)\n- Breakthrough migraine attacks: Shorter duration at moderate+ pain intensity (-1.07 hours, p=0.013) and lower peak pain intensity (-0.48, p=0.011)\n- Safety: Grade 3 adverse events 1.6% vs 1.2% placebo; no grade 4 or fatal events\n- Study conducted at 61 sites across North America and Europe (2020-2023)","whyItMatters":"This study fundamentally shifts how we measure migraine treatment success. Rather than just counting headache days (which treats all migraines equally), EMBRACE measured what matters most to patients: how long they suffer, how bad it gets, and whether they can function at work, socially, and emotionally. The results show erenumab doesn't just prevent some migraines — it also makes the ones that break through shorter and less severe, providing a more complete picture of treatment benefit. This approach could change how future migraine drugs are evaluated.","specificNumbers":"","methodology":"EMBRACE was a Phase 4, interventional, double-blind, randomized, placebo-controlled, multicenter global study conducted at 61 sites in North America and Europe from September 2020 to October 2023. Adults with high-frequency episodic migraine (8-14 monthly migraine days) and at least one failed prior preventive treatment were randomized to erenumab 140 mg or placebo subcutaneously once monthly for 4 months. The primary endpoint was change in monthly hours of moderate-to-severe headache pain (months 1-3). Secondary endpoints included functional impact (MFIQ four domains), breakthrough migraine duration and intensity. Only patients with at least one qualifying triptan-treated attack at baseline were included.","limitations":"The 4-month treatment period is relatively short for a chronic condition; longer studies would assess durability. Only erenumab 140 mg was tested (not the 70 mg dose). The study enrolled only patients with high-frequency episodic migraine (8-14 days/month), so results may not apply to chronic migraine (≥15 days/month) or lower-frequency patients. The requirement for a qualifying triptan-treated attack at baseline may have selected for patients with a specific migraine profile. The study was conducted during the COVID-19 pandemic (2020-2023), which may have affected patient behavior and reporting."},{"rthcId":"RPEP-15846","title":"Identification of antihypertensive peptides from Eudrilus eugeniae (Kinberg, 1867): in vitro ACE-I inhibition and peptide profiling.","authors":"Pajimna, Roi Martin B; Villalobos, Omar A; Lirio, Stephen B; Huang, Hsi-Ya; Lin, Chia-Her; Macabeo, Allan Patrick; Corpuz, Mary-Jho Anne T; Villaflores, Oliver B","year":2026,"journal":"Natural product research, 1-7","doi":"10.1080/14786419.2026.2613336","pmid":"41505708","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15847","title":"Screening for Peptides to Bind and Functionally Inhibit SARS-CoV-2 Fusion Peptide Using Mirrored Combinatorial Phage Display and Human Proteomic Phage Display.","authors":"Pal, Ajay; Roy, Neeladri Sekhar; Angeliadis, Matthew; Madhu, Priyanka; O'Reilly, Sophie; Bera, Indrani; Francois, Nathan; Lynch, Aisling; Gautier, Virginie; Devocelle, Marc; O'Connell, David J; Shields, Denis C","year":2026,"journal":"Molecules (Basel, Switzerland), 31(2)","doi":"10.3390/molecules31020282","pmid":"41599331","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15848","title":"Neuropeptide Y at the crossroads of neurodegeneration: Mechanistic insights and emerging therapeutic strategies.","authors":"Palanivel, Viswanthram; Salkar, Akanksha; Shenoy, Avinash; Eva, Taslima Akter; Perera, Rumandee; Chitranshi, Nitin; Gupta, Veer; You, Yuyi; Mirzaei, Mehdi; Graham, Stuart L; Gupta, Vivek; Basavarajappa, Devaraj","year":2026,"journal":"Neuropeptides, 115, 102583","doi":"10.1016/j.npep.2025.102583","pmid":"41468784","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review synthesizes evidence showing NPY's dual role in neurodegeneration:\n\n1. **As a biomarker**: NPY expression is altered in Alzheimer's, Parkinson's, Huntington's, ALS, Machado-Joseph disease, diabetic retinopathy, and glaucoma, potentially serving as a marker for disease progression.\n\n2. **As a neuroprotective agent**: NPY alleviates excitotoxicity, oxidative stress, mitochondrial dysfunction, and neuroinflammation while promoting neurogenesis, synaptic plasticity, and cellular resilience.\n\n3. **Through specific signaling cascades**: NPY acts via PI3K/Akt, MAPK/ERK, and p38K pathways through its receptor subtypes to control cell survival, protein homeostasis (proteostasis), and inflammation.","whyItMatters":"Neurodegenerative diseases collectively affect tens of millions of people worldwide with limited treatment options. Finding that a single neuropeptide system is dysregulated across so many different conditions suggests a shared vulnerability that could be addressed therapeutically. NPY's neuroprotective actions through multiple independent mechanisms (anti-excitotoxic, antioxidant, anti-inflammatory, pro-neurogenic) make it an unusually versatile therapeutic target.","specificNumbers":"","methodology":"This is a narrative review compiling published evidence on neuropeptide Y's roles in neurodegeneration, covering its expression changes across multiple diseases and the molecular mechanisms underlying its neuroprotective effects.","limitations":"This is a narrative review, not a systematic review, so coverage may be selective. Most of the neuroprotective evidence comes from cell culture and animal models, with limited human clinical data. The diversity of diseases covered is broad, which may obscure important disease-specific differences in NPY biology. Translating NPY-based therapies to clinical use faces challenges including blood-brain barrier delivery and potential metabolic side effects."},{"rthcId":"RPEP-15849","title":"Assessing Nutraceuticals for Hepatic Steatosis: A Standardized In Vitro Approach.","authors":"Palasantzas, Victoria E J M; Struik, Dicky; Bos, Trijnie; Withoff, Sebo; Fu, Jingyuan; Jonker, Johan W; Hoogerland, Joanne A","year":2026,"journal":"Nutrients, 18(3)","doi":"10.3390/nu18030388","pmid":"41683214","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15850","title":"Expression of Calca gene-derived peptides in the murine taste system.","authors":"Palayyan, Salin Raj; Siddiqui, Abdul Hamid; Sukumaran, Sunil Kumar","year":2026,"journal":"bioRxiv : the preprint server for biology","doi":"10.64898/2026.01.16.700005","pmid":"41648232","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15851","title":"Anti-virulence activity and immunomodulation of Oreoch-1 against enteroinvasive Escherichia coli infection.","authors":"Palma, Francesca; Giugliano, Rosa; Chianese, Annalisa; Della Marca, Roberta; Monti, Alessandra; Doti, Nunzianna; Zannella, Carla; Galdiero, Massimiliano; De Filippis, Anna","year":2026,"journal":"Microbial pathogenesis, 211, 108253","doi":"10.1016/j.micpath.2025.108253","pmid":"41456688","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Oreoch-1, a 23-amino-acid cationic peptide from Nile tilapia, demonstrated anti-virulence activity against enteroinvasive E. coli (EIEC) at concentrations of 6.25-12.5 μM. Rather than killing bacteria directly, the peptide interfered with EIEC's invasion process in colon cells (Caco-2). Oreoch-1 modulated expression of seven key virulence factors (ial, icsA, icsB, ipaB, ipaC, virB, virF) and five inflammatory cytokines (IL-6, IL-8, IL-1β, TNF-α, TGF-β).\n\nThis dual action — reducing bacterial virulence while modulating the host inflammatory response — represents a fundamentally different approach from conventional antibiotics that simply try to kill bacteria.","whyItMatters":"Antibiotic resistance is one of the biggest threats to global health, and EIEC outbreaks are becoming harder to treat. Anti-virulence strategies are gaining attention because they 'disarm' bacteria without killing them, reducing selective pressure for resistance development. Finding that a fish-derived peptide can both downregulate bacterial virulence genes and calm the host inflammatory response addresses the infection from two angles simultaneously — making it a particularly promising candidate for resistant infection management.","specificNumbers":"23 amino acids · 3.125-25 μM concentration range · Active at 6.25-12.5 μM · 7 virulence factors modulated · 5 cytokines assessed · Caco-2 colon cell model","methodology":"Oreoch-1 was tested against EIEC ATCC 43983 using broth microdilution for antimicrobial activity. Anti-virulence effects were assessed in Caco-2 colon cancer cells by measuring EIEC invasion efficiency after peptide treatment. Expression of seven EIEC virulence genes was measured by qPCR. Host inflammatory response was assessed by measuring five cytokines in infected Caco-2 cells treated with Oreoch-1.","limitations":"All experiments were in vitro using a single EIEC strain and one cell line (Caco-2). The direct antimicrobial activity was described as 'slight,' so the peptide primarily works through anti-virulence rather than killing. In vivo efficacy, stability in the gut environment, toxicity, and effects on normal gut microbiota were not tested. The specific mechanisms by which Oreoch-1 modulates virulence gene expression and cytokine production were not elucidated."},{"rthcId":"RPEP-15852","title":"Metabolic and hormonal effects of whole grains of rye, oats and wheat in dog food.","authors":"Palmqvist, Hanna; Ringmark, Sara; Dicksved, Johan; Lundh, Torbjörn; Höglund, Katja","year":2026,"journal":"Journal of animal science, 104","doi":"10.1093/jas/skaf447","pmid":"41410534","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15853","title":"Glucagon-Like Peptide-1 Receptor Agonists and Alcohol Use: A Real-Word Observational Study in a Large, Integrated Health Care System.","authors":"Palzes, Vanessa A; Costales, Brianna; Sterling, Stacy; Kline-Simon, Andrea; Leggio, Lorenzo; Farokhnia, Mehdi","year":2026,"journal":"Biological psychiatry global open science, 6(2), 100659","doi":"10.1016/j.bpsgos.2025.100659","pmid":"41552778","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15854","title":"Flexible dose of semaglutide reduces early discontinuation while maintaining comparable outcomes in obese patients: FLEX-SEMA 2.4 mg, an Italian real-world study.","authors":"Pampanelli, Simone; Terzoni, Stefano; Pantanetti, Paola; Di Loreto, Chiara; Mazzieri, Alessio; Cangelosi, Giovanni; Alberti, Sara; Badiali, Cristina; Grandone, Ilenia; Migliarelli, Sara; Castagna, Maria Grazia; Cerrai Ceroni, Mariaclaudia; Benenati, Nicoletta","year":2026,"journal":"Diabetes, obesity & metabolism","doi":"10.1111/dom.70538","pmid":"41725422","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15855","title":"Evaluation of the relationship between salivary levels of Streptococcus mutans, statherin, and cathelicidin LL-37 and early childhood caries.","authors":"Pamuk, Ceren; Ersin, Nazan; Emingil, Gülnur; Ozdemir, Güven; Vural, Caner; Vural, Cansu; Gül, Aytül; Çelik, Handan; Gezgin, Yüksel","year":2026,"journal":"BMC oral health","doi":"10.1186/s12903-026-07819-4","pmid":"41656215","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15856","title":"Engineering Smart Bimetallic Ionic-Site MOF Nanozyme Nanocomposites for Microenvironment-Responsive Dynamic Therapy of Periapical Periodontitis.","authors":"Pan, Meng-Meng; Ye, Wei-Hu; Zhang, Run-Ze; Hu, Jin-Xuan; Xie, Yuchen; Wang, Min; Xia, Haibin; Chen, Huiping; Yang, Yang; Xu, Li; Yu, Xu; Chen, Liang-Wen","year":2026,"journal":"ACS nano","doi":"10.1021/acsnano.5c18916","pmid":"41733099","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15857","title":"Obesity in China: current progress and future prospects.","authors":"Pan, Xiong-Fei; Fang, Zhong-Ze; Zhang, Lingli; Pan, An","year":2026,"journal":"The lancet. Diabetes & endocrinology, 14(2), 178-186","doi":"10.1016/S2213-8587(25)00357-2","pmid":"41389801","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15858","title":"Development of a lymph node-homing peptide vaccine targeting C-C chemokine receptor 7-positive dendritic cells with enhanced antitumor immunity.","authors":"Pang, Liwei; Wang, Mingshuang; Fan, Jiani; Sun, Yingjie; Han, Jingjing; Shen, Wenhui; Yang, Bingqian; Hu, Xiaonan; Sun, Yixuan; Kong, Yanan; Qi, Yuanming; Wu, Yahong; Gao, Yanfeng","year":2026,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 391, 114645","doi":"10.1016/j.jconrel.2026.114645","pmid":"41580130","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Using phage display, the team identified a peptide (CRBP3) that specifically binds CCR7 and is internalized by both immature and mature dendritic cells. After footpad injection, CRBP3 accumulated in popliteal lymph nodes.\n\nWhen conjugated to the OVA257-264 antigen, the CRBP3-OVA257-264 vaccine significantly increased MHC-I/peptide complex formation on dendritic cells and boosted IFN-γ production and proliferation of antigen-specific CD8+ T cells. In tumor models, CRBP3-conjugated vaccines carrying either OVA257-264 or HPV16 E749-57 peptides produced potent antitumor responses. The CRBP3-E749-57 vaccine achieved complete tumor regression in TC-1 tumor-bearing mice — a model resistant to anti-PD-1 checkpoint blockade — and conferred long-lasting protection against tumor rechallenge.","whyItMatters":"Cancer vaccines often fail because antigens don't reach the lymph nodes efficiently. By using a peptide that naturally homes to lymph nodes via CCR7, this approach could make peptide-based cancer vaccines far more potent — and the fact that it worked in an anti-PD-1-resistant tumor model suggests it could complement or even substitute for checkpoint immunotherapy in hard-to-treat cancers.","specificNumbers":"","methodology":"The researchers used phage display technology to screen for peptides that bind CCR7, then validated the top candidate (CRBP3) with binding assays on dendritic cells. They tested lymph node accumulation in mice via footpad injection, measured MHC-I complex formation and T cell activation in vitro, and evaluated antitumor efficacy in two mouse tumor models: anti-PD-1-responsive B16-OVA melanoma and anti-PD-1-resistant TC-1 cervical cancer.","limitations":"All efficacy data come from mouse tumor models, which don't always predict human outcomes. The study did not evaluate toxicity in detail, and the specific doses and schedules may not translate directly to human use. CCR7 expression patterns on human dendritic cells may differ from mice, potentially affecting targeting efficiency."},{"rthcId":"RPEP-15859","title":"Retatrutide in type 2 diabetes mellitus and obesity: an overview.","authors":"Panou, Theodoros; Gouveri, Evanthia; Popovic, Djordje S; Papanas, Nikolaos","year":2026,"journal":"Expert review of clinical pharmacology","doi":"10.1080/17512433.2026.2642415","pmid":"41785010","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15860","title":"M14 substitutions in exanatide modulate alpha-synuclein aggregation.","authors":"Panuganti, Venkataharsha; Manchanda, Kanika; Bharatam, Prasad V; Roy, Ipsita","year":2026,"journal":"The FEBS journal, 293(5), 1415-1432","doi":"10.1111/febs.70321","pmid":"41206637","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15861","title":"Tumor Targeting with Peptide-Drug Conjugates: Showcasing Key Progress and Hurdles.","authors":"Parang, Keykavous; Do, Thuy; Dinh, Clare; Davani-Davari, Dorna; Foroughi, Max; Khong, Troy; Moazen, Mahsa; Nasrolahi Shirazi, Amir","year":2026,"journal":"Drug design, development and therapy, 20, 562135","doi":"10.2147/DDDT.S562135","pmid":"41710577","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"PDCs are small (~1-3 kDa) targeted therapeutics that use homing peptides to deliver cytotoxic drugs to tumors, offering superior tissue penetration and faster clearance compared to antibody-drug conjugates (ADCs, ~150 kDa). Currently, only one PDC is FDA-approved: lutetium (177Lu)-DOTATATE (Lutathera) for neuroendocrine tumors. Other PDCs in development include paclitaxel-Angiopep-2 (ANG1005) for brain tumors and LyP-1-doxorubicin conjugates for triple-negative breast cancer. Key challenges remain: premature drug release, metabolic clearance, variable receptor expression across tumors, and manufacturing scale-up. Melflufen, another PDC, faced clinical setbacks.","whyItMatters":"Antibody-drug conjugates (ADCs) are already a multi-billion-dollar cancer drug class, but their large size limits how deeply they penetrate tumors. PDCs are essentially the smaller, nimbler cousin — they can reach parts of tumors that antibodies can't and are cheaper to manufacture. With only one FDA-approved PDC so far, the field is still early but has enormous potential, especially with AI-assisted design and theranostic (imaging + therapy) approaches emerging.","specificNumbers":"PDCs: ~1-3 kDa · ADCs: ~150 kDa · 1 FDA-approved PDC (Lutathera) · Mechanisms: receptor binding, endocytosis, stimuli-responsive release · Self-assembly capability","methodology":"Comprehensive narrative review covering PDC design principles (targeting peptides, linker chemistry, drug payloads), mechanisms of tumor delivery and drug release, specific clinical examples, comparison with ADCs, current challenges, and future directions including AI-assisted design and theranostic applications.","limitations":"This is a review article, not an experimental study. The field faces significant practical challenges: only one PDC has achieved FDA approval while others (like melflufen) have failed or stalled. The advantages of PDCs over ADCs (better penetration, cheaper manufacturing) must be weighed against disadvantages (faster clearance means shorter drug exposure, potentially requiring more frequent dosing)."},{"rthcId":"RPEP-15862","title":"Effect of Tirzepatide on the Risk of Developing Type 2 Diabetes Mellitus Among the People Living With Obesity or Overweight: A Systematic Review.","authors":"Pardeshi, Geeta; Kumbhar, Uddhav T; Kaviprawin, Mogan; Debnath, Aninda; Dubey, Ashok Kumar; Deshmukh, Kalyani; Goyal, Chanchal; Gandhi, Aravind P","year":2026,"journal":"Clinical obesity, 16(1), e70042","doi":"10.1111/cob.70042","pmid":"40832978","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Three eligible studies (one RCT and two cohort studies) provided data on tirzepatide's diabetes prevention effects:\n\nTirzepatide vs. placebo:\n- At 176 weeks (~3.4 years): HR = 0.07 (95% CI: <0.01-0.1; P<0.001) — a 93% risk reduction\n- At 193 weeks (~3.7 years): HR = 0.12 (95% CI: 0.1-0.2; P<0.001) — an 88% risk reduction\n\nTirzepatide vs. semaglutide:\n- At 12 months: HR = 0.73 (95% CI: 0.58-0.92; P<0.001) — a 27% risk reduction\n\nAll comparisons were statistically significant. The hazard ratios against placebo are particularly dramatic, suggesting tirzepatide nearly eliminates the risk of diabetes progression in the treatment period.","whyItMatters":"About 96 million American adults have prediabetes, and up to 70% of them will eventually develop type 2 diabetes. Preventing that transition — rather than treating diabetes after it develops — could fundamentally change the trajectory of one of the world's most prevalent chronic diseases. A 93% risk reduction with tirzepatide suggests that for many people, type 2 diabetes could become a preventable disease rather than an inevitable consequence of obesity.","specificNumbers":"","methodology":"This was a systematic review following PRISMA guidelines, registered on PROSPERO (CRD42024614466). Six databases (PubMed, ClinicalTrials.gov, EMBASE, Scopus, Web of Science, Cochrane Library) were searched through July 10, 2025. Two-stage dual screening with third-person adjudication was used. Study quality was assessed using RoB 2.0 for RCTs and Newcastle-Ottawa Scale for cohort studies. Three studies were eligible: one randomized controlled trial and two cohort studies. Hazard ratios for new-onset diabetes were the primary outcome.","limitations":"Only three studies met inclusion criteria, and only one was a randomized controlled trial — the other two were cohort studies with inherent confounding risks. The diabetes prevention findings come from secondary or post hoc analyses of trials primarily designed for other endpoints (weight loss, metabolic improvement). The very low hazard ratios (0.07, 0.12) should be interpreted cautiously given the small number of studies. Cost, insurance coverage, and treatment durability after discontinuation are not addressed. Long-term data beyond 4 years is not available."},{"rthcId":"RPEP-15863","title":"Exenatide induces an Enhanced Endogenous Glucagon-like Peptide-1 Secretory Response in Patients receiving Basal Insulin.","authors":"Parikh, Mihir; MMath, Jiajie Pu; Shen, Junwei; Kramer, Caroline K; Zinman, Bernard; Beaudry, Jacqueline L; Retnakaran, Ravi","year":2026,"journal":"The Journal of clinical endocrinology and metabolism","doi":"10.1210/clinem/dgag033","pmid":"41604435","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15864","title":"Sodium-Glucose Cotransporter 2 Inhibitors, Glucagon-Like Peptide 1 Receptor Agonists, and Frailty Progression in Older Adults With Type 2 Diabetes.","authors":"Park, Chan Mi; Thanapluetiwong, Saran; Chen, Xiecheng; Oh, Gahee; Ko, Darae; Kim, Dae Hyun","year":2026,"journal":"Diabetes care, 49(1), 147-151","doi":"10.2337/dc25-1031","pmid":"41232081","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Using a 7% random sample of Medicare data comparing new users of four diabetes drug classes, GLP-1RA users showed a significantly lower mean frailty index change of -0.007 (95% CI: -0.011 to -0.004) and SGLT-2i users showed -0.005 (95% CI: -0.008 to -0.002) compared to DPP-4i users over one year. Sulfonylurea users showed no significant difference from DPP-4i users.\n\nMediation analyses revealed that these associations were minimally mediated by cardiovascular or safety events, suggesting the anti-frailty effects operate through independent mechanisms such as metabolic improvements, inflammation reduction, or body composition changes.","whyItMatters":"Frailty is a major concern for older adults with diabetes, as it increases the risk of falls, hospitalization, disability, and death. If GLP-1 receptor agonists can slow frailty beyond their known cardiovascular and metabolic benefits, this adds another important reason to consider these peptide-based therapies in older patients — a population often underrepresented in clinical trials.","specificNumbers":"","methodology":"This was a retrospective cohort study using a 7% random sample of Medicare claims data. Researchers compared new users of DPP-4 inhibitors (active comparator), GLP-1RAs, SGLT-2is, and sulfonylureas. Frailty was measured using a validated claims-based frailty index (CFI, range 0-1). The primary outcome was 1-year change in CFI. Mediation analyses assessed whether cardiovascular events or safety events explained the observed differences.","limitations":"This is a retrospective observational study using claims data, which cannot establish causation. The claims-based frailty index is a proxy measure and may not capture all dimensions of frailty. Confounding by indication is possible — sicker patients may preferentially receive certain drug classes. The one-year follow-up is relatively short for assessing frailty trajectories. Specific GLP-1RA agents were not differentiated."},{"rthcId":"RPEP-15865","title":"A Novel Peptide, HS1002, Enhances Antitumor Activity via Dual Targeting of the GnRH Receptor and Human Telomerase Reverse Transcriptase in Prostate Cancer Cells.","authors":"Park, Jae Hyeon; Lee, Joo Chan; Sharma, Swati; Jiang, Chunxue; Lee, Haeun; Park, Hyun-Ju; Kim, Hyung Sik","year":2026,"journal":"MedComm, 7(3), e70630","doi":"10.1002/mco2.70630","pmid":"41700173","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15866","title":"Charge-based supramolecular peptide nanocomplexes for oral delivery via transporter-driven endocytosis.","authors":"Park, So-Hyeon; Ma, Gaeun; Park, Seong Jin; Yang, Seong-Bin; Seo, Minho; Lee, Jun-Hyuck; Kweon, Seho; Park, Jooho","year":2026,"journal":"Biomaterials, 329, 123903","doi":"10.1016/j.biomaterials.2025.123903","pmid":"41411844","tags":["peptide-drug-delivery","glp-1-agonists"],"studyType":"animal-and-cell","evidenceStrength":"preliminary","keyFinding":"Researchers engineered positively charged bile acid-peptide conjugates (PCBs) that self-assemble with negatively charged semaglutide through electrostatic interactions, forming stable nanoparticles approximately 279 nm in size. The best candidate, PCB4, created 'PBSG nanocomplexes' that significantly enhanced semaglutide's absorption through the intestinal wall via bile acid transporter-driven endocytosis.\n\nIn a high-fat diet mouse model, oral PBSG nanocomplexes improved semaglutide's therapeutic efficacy compared to unformulated semaglutide. The nanocomplexes also elevated GLP-1 expression in vivo through a dual mechanism: directly delivering semaglutide and simultaneously modulating bile acid metabolism. This approach hijacks the body's own bile acid transport system to shuttle peptide drugs across the intestinal barrier.","whyItMatters":"Semaglutide's biggest limitation is its delivery: the injectable form (Ozempic/Wegovy) requires needles, while the current oral form (Rybelsus) has very low bioavailability (~1%) and requires strict fasting before taking it. A nanoparticle delivery system that dramatically improves oral peptide absorption could make semaglutide — and potentially other peptide drugs — much more effective when taken by mouth. Using bile acid transporters as a natural uptake pathway is elegant because these transporters are specifically designed to absorb bile acids from the gut, providing a pre-built highway for drug delivery.","specificNumbers":"PBSG nanocomplexes: ~279 nm average size · bile acid transporter-driven endocytosis · improved GI permeation and oral absorption · enhanced efficacy in HFD mouse model · dual action: semaglutide delivery + bile acid metabolism modulation · GLP-1 expression elevated in vivo","methodology":"The researchers synthesized a series of positively charged peptide-engineered bile acids (PCBs) and screened them for ability to form stable nanocomplexes with semaglutide. Intestinal permeability was tested in Caco-2 cells and intestinal tissue. In vivo efficacy was evaluated in C57BL mice fed a high-fat diet, comparing oral PBSG nanocomplexes to controls. Bile acid transporter activity and GLP-1 expression were measured to characterize the mechanism.","limitations":"This is a preclinical study in mice and cell cultures. The critical metric — oral bioavailability improvement as a percentage — is not quantified in the abstract. Long-term safety of repeatedly administering bile acid-modified nanoparticles is unknown. Manufacturing scalability and stability under storage conditions are not addressed. Comparison to the existing commercial oral semaglutide formulation (Rybelsus with SNAC enhancer) was not reported."},{"rthcId":"RPEP-15867","title":"Early mechanisms of diabetes development in pediatric pancreatitis: A pilot study.","authors":"Parra Villasmil, Maria Graciela; Bellin, Melena; Pinnaro, Catherina; Craighead, Fati; Cress, Gretchen; Uc, Aliye; Lowe, Mark; Hodges, James S; Ode, Katie Larson","year":2026,"journal":"Journal of pediatric gastroenterology and nutrition, 82(2), 549-556","doi":"10.1002/jpn3.70263","pmid":"41251022","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15868","title":"A Review of the Management of Obesity in Primary Care.","authors":"Parretti, H M; Erskine, S E; Coulman, K D; Mears, R; Clare, K; Williamson, K; Watkins, R; Hughes, C A","year":2026,"journal":"Clinical obesity, 16(1), e70040","doi":"10.1111/cob.70040","pmid":"40831325","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15869","title":"Efficacy and Safety of GLP-1 Receptor Agonists for the Management of Antipsychotic-Induced Weight Gain.","authors":"Pascale, Sarah; Reinert, Justin P","year":2026,"journal":"The Annals of pharmacotherapy, 10600280251414107","doi":"10.1177/10600280251414107","pmid":"41723102","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15870","title":"Changes to insulin requirements over time with semaglutide in adults with type 1 diabetes on insulin pump therapy: A post-hoc analysis of a double-blinded, randomised, crossover trial.","authors":"Pasqua, Melissa-Rosina; Tsoukas, Michael A; Haidar, Ahmad","year":2026,"journal":"Diabetes, obesity & metabolism, 28(1), 427-433","doi":"10.1111/dom.70213","pmid":"41144928","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 26 adults with type 1 diabetes on insulin pump therapy, semaglutide rapidly reduced total and bolus insulin requirements — significantly by day 7 — while basal insulin reductions became significant by day 32. By day 77, carbohydrate ratios increased 4.1%, correction factors increased 11.2%, and basal rates decreased 7.9%. The insulin reductions were primarily driven by reduced food intake (less carbohydrate consumption) rather than improved insulin sensitivity.\n\nDespite these rapid changes, hypoglycemia was rarely above 4% of time during follow-ups, suggesting that CGM and automated insulin delivery technology helped mitigate hypoglycemia risk — though active pump parameter adjustments were still needed.","whyItMatters":"Semaglutide is not approved for type 1 diabetes, but its appetite-suppressing effects are leading to off-label use in T1D patients with overweight/obesity. This study reveals how quickly insulin needs change — within the first week — creating a hypoglycemia risk if pump settings aren't adjusted promptly. The data provides practical guidance for the growing number of T1D patients and clinicians using GLP-1 peptide drugs off-label alongside insulin pumps.","specificNumbers":"n=26 · Bolus insulin reduced by day 7 · Basal reduced by day 32 · Carb ratios +4.1% · Correction factors +11.2% · Basal rates -7.9% · Hypo time rarely >4% · 81% on AID at baseline","methodology":"Post-hoc analysis of a double-blinded, randomized, crossover trial comparing semaglutide (up to 1 mg) versus placebo in T1D adults on insulin pump therapy with CGM. The first 11 of 15 weeks were analyzed, during which participants used routine pump therapy. Remote follow-ups were conducted at days 7, 21, 32, 56, 63, and 77. Changes in total, basal, and bolus insulin; carbohydrate input; and pump parameters were assessed relative to baseline.","limitations":"Small sample (n=26). Post-hoc analysis — the trial was not designed to specifically study insulin requirement changes. Only 11 of 15 weeks analyzed. The crossover design means each participant received both semaglutide and placebo, but the analysis focused on semaglutide periods. Results may not generalize to patients without CGM or automated insulin delivery, where hypoglycemia risk would likely be higher. Semaglutide is off-label in T1D."},{"rthcId":"RPEP-15871","title":"Semaglutide Use With Automated Insulin Delivery in Adults With Type 1 Diabetes: Qualitative Analyses and Patient-reported Outcomes From a Randomized Controlled Trial.","authors":"Pasqua, Melissa-Rosina; Doumat, Joelle; Tsoukas, Michael A; Haidar, Ahmad","year":2026,"journal":"Canadian journal of diabetes, 50(1), 38-46.e5","doi":"10.1016/j.jcjd.2025.10.175","pmid":"41175929","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15872","title":"Engineered α-Helical Peptides with Chelating Agents as Approach to Antibacterial Therapeutics.","authors":"Patamia, Vincenzo; Saccullo, Erika; Larocca, Michele; Fuochi, Virginia; Furnari, Salvatore; Furneri, Pio Maria; Cilibrizzi, Agostino; Floresta, Giuseppe","year":2026,"journal":"ChemistryOpen, 15(1), e202500588","doi":"10.1002/open.202500588","pmid":"41505789","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15873","title":"Calcitonin gene-related peptide in the audiovestibular system.","authors":"Patel, Evan J; Sharon, Jeffrey D; Levin, Morris; Luebke, Anne E","year":2026,"journal":"Headache, 66(1), 278-285","doi":"10.1111/head.15075","pmid":"41137472","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15874","title":"Early Experience Treating Vestibular Migraine With Small Molecule CGRP Antagonists.","authors":"Patel, Evan J; Koziol, Kali; Sharon, Jeffrey D","year":2026,"journal":"Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery","doi":"10.1002/ohn.70196","pmid":"41774573","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15875","title":"A single-center retrospective review of food retention during upper endoscopy following GLP-1 receptor agonist usage and introduction of the Tampa Intraluminal Gastric Residue (TiGR) grading scale.","authors":"Patel, Yash; McDonald, Alice; Taylor, George Malcolm; Sher, Theo; DuCoin, Christopher; Sujka, Joseph; Docimo, Salvatore","year":2026,"journal":"Surgical endoscopy","doi":"10.1007/s00464-026-12640-9","pmid":"41772229","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15876","title":"Metabolic Inflammation as a Common Thread in Cardio-Endocrine Diseases: Toward a Unified Therapeutic Framework.","authors":"Patil, Nidhi; Uppal, Neha; Bedi, Simranjeet; Undhad, Hiral; Joshi, Pooja","year":2026,"journal":"Cureus, 18(1), e102160","doi":"10.7759/cureus.102160","pmid":"41732594","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15877","title":"Glucagon-like peptide 1 receptor agonists in substance use disorders: A systematic review of ClinicalTrials.Gov.","authors":"Patil, Shruti; Jha, Nandini; Jha, Manish K","year":2026,"journal":"Addictive behaviors reports, 23, 100671","doi":"10.1016/j.abrep.2026.100671","pmid":"41696398","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15878","title":"Effect of GLP-1 Receptor Agonists on Patients with Thyroid Carcinomas Undergoing Active Surveillance.","authors":"Patrizio, Armando; Newman, Samantha K; Tuttle, R Michael; Boucai, Laura","year":2026,"journal":"Journal of the Endocrine Society, 10(1), bvaf182","doi":"10.1210/jendso/bvaf182","pmid":"41376649","tags":["glp-1-agonists"],"studyType":"Retrospective Observational Cohort Study","evidenceStrength":"moderate","keyFinding":"GLP-1 receptor agonists did not accelerate the growth of low-risk papillary thyroid carcinomas. After a median of 25 months on GLP-1RA therapy and 5.5 years of follow-up, 84.2% of tumors in the GLP-1RA group remained stable, compared to 92.1% in the unexposed group — a difference that was not statistically significant (p=0.53).\n\nAmong the two tumors in the GLP-1RA group that did grow, the drug did not alter their growth kinetics (they were already growing before GLP-1RA exposure). This provides early reassurance that GLP-1 drugs don't fuel thyroid cancer growth.","whyItMatters":"GLP-1 drugs like semaglutide and tirzepatide carry FDA-mandated warnings about thyroid C-cell tumors based on rodent studies. With millions of patients now taking these drugs, there's intense interest in whether they actually affect thyroid cancer risk in humans. This study specifically addresses whether GLP-1RAs make existing thyroid cancers grow faster — and finds no evidence they do.","specificNumbers":"n=18 GLP-1RA patients (19 tumors) vs n=37 controls (38 tumors) · median 25 months GLP-1RA exposure · median 5.5 years follow-up · 84.2% stable on GLP-1RA vs 92.1% stable controls · p=0.53","methodology":"Retrospective cohort study at a single tertiary center. 18 patients with small (≤1.5 cm) papillary thyroid carcinomas on active surveillance who were exposed to GLP-1RAs were matched 1:2 by BMI and tumor size to 37 unexposed patients. Researchers tracked tumor growth using diameter changes (≥3 mm) and volume changes (>72%). Volume doubling time was calculated for a subset of patients before and during GLP-1RA therapy.","limitations":"Very small sample size (18 exposed patients). Retrospective design at a single center. Only low-risk papillary thyroid carcinomas (≤1.5 cm) were studied — results may not apply to larger or more aggressive thyroid cancers. Median GLP-1RA exposure was only 25 months. The study was underpowered to detect small differences in growth rates."},{"rthcId":"RPEP-15879","title":"Oxytocin beyond social bonding: Advancing neuromodulation, synaptic plasticity, and epigenetic precision in CNS disorders.","authors":"Paul, Supratim; Verma, Janvi; Mehan, Sidharth","year":2026,"journal":"Neuropeptides, 116, 102597","doi":"10.1016/j.npep.2026.102597","pmid":"41759439","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15880","title":"Immune-Modulatory Effects of Bioactive Collagen Peptides Improve Skin Health in Middle-Aged Women.","authors":"Paula-Vieira, Rosa Helena Ramos; Dias, Sandra Regina; Silva-Reis, Anamei; Moura-Maia, Meiry Souza; Ramos-Gomes, Nycole Vieira; Jesus-Silva, Kananda; Oliveira-Leal, Yasmim Rodrigues; Castro-Pimentel, Laura Thaís; Carvalho, Wany Soares Fagundes; Melo, Flavia; Martins, José Luis Rodrigues; Bachi, André Luis Lacerda; Vieira, Rodolfo P","year":2026,"journal":"Dermatology and therapy, 16(2), 1385-1397","doi":"10.1007/s13555-026-01654-9","pmid":"41588262","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15881","title":"Vascular and Myocardial Function in Patients with Type 2 Diabetes and Ischemic Stroke Treated with Dulaglutide or Empagliflozin.","authors":"Pavlidis, George; Prentza, Vasiliki; Ikonomidis, Ignatios; Katogiannis, Konstantinos; Kountouri, Aikaterini; Thymis, John; Michalopoulou, Eleni; Pliouta, Loukia; Korakas, Emmanouil; Stefanou, Maria-Ioanna; Palaiodimou, Lina; Tsivgoulis, Georgios; Lambadiari, Vaia","year":2026,"journal":"Medicina (Kaunas, Lithuania), 62(2)","doi":"10.3390/medicina62020254","pmid":"41752654","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15882","title":"Nanoparticle-mediated antagonism of sustained endosomal signaling of the calcitonin receptor-like receptor provides enhanced and persistent relief of oral cancer pain.","authors":"Peach, Chloe J; Tu, Nguyen Huu; Lewis, Parker K; Pollard, Rachel E; Sokrat, Badr; Nicholson, Sam; Trevett, Kai; Barrett, Naomi; De Logu, Francesco; Zhu, Jiaqi; Latorre, Rocco; Teng, Shavonne; Therien, Michael J; Jensen, Dane D; Schmidt, Brian L; Bunnett, Nigel W; Pinkerton, Nathalie M","year":2026,"journal":"Biomaterials, 327, 123757","doi":"10.1016/j.biomaterials.2025.123757","pmid":"41092649","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15883","title":"The effect of obesity interventions on male fertility: a systematic review and meta-analysis.","authors":"Peel, Andrew; Lyons, Hannah; Tully, Cathryn A; Vincent, Andrew D; Jesudason, David; Wittert, Gary; McPherson, Nicole O","year":2026,"journal":"Human reproduction update, 32(2), 154-180","doi":"10.1093/humupd/dmaf025","pmid":"41065428","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15884","title":"Medication-overuse headache: can anti-CGRP monoclonal antibodies replace withdrawal?","authors":"Pellesi, Lanfranco; Lo Castro, Flavia; Boccalini, Alberto; Allamprese, Rossana; Guerzoni, Simona","year":2026,"journal":"Expert review of neurotherapeutics, 26(1), 67-74","doi":"10.1080/14737175.2025.2596783","pmid":"41313646","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15885","title":"Positioning rimegepant in migraine prophylaxis: updated evidence and emerging perspectives.","authors":"Pellesi, Lanfranco; Scuteri, Damiana; Martelletti, Paolo","year":2026,"journal":"Expert review of neurotherapeutics, 1-9","doi":"10.1080/14737175.2026.2621879","pmid":"41578960","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Rimegepant is positioned as a significant addition to migraine prophylaxis, distinguished by its dual use for both acute and preventive treatment — a capability unique among CGRP-targeting therapies. The review integrates evidence through 2025 and identifies several emerging directions:\n\n- Situational prevention (using rimegepant around known migraine triggers)\n- Potential combination with traditional preventives or anti-CGRP monoclonal antibodies\n- Exploratory use in other CGRP-mediated headache disorders beyond migraine\n\nThe drug is described as well-tolerated with a favorable safety profile, though long-term persistence and safety monitoring remain important.","whyItMatters":"CGRP-targeting therapies have transformed migraine treatment, but most preventive options are injectable monoclonal antibodies requiring monthly or quarterly administration. Rimegepant offers an oral alternative that patients can use flexibly — both for acute attacks and prevention — potentially improving adherence and quality of life. Its ability to serve as a bridge between acute and preventive care is a paradigm shift in migraine management.","specificNumbers":"","methodology":"This is a narrative review with literature identified through PubMed/MEDLINE and Scopus searches (last search: November 19, 2025) using predefined search terms related to rimegepant and migraine. The review synthesizes pharmacological, clinical, safety, and regulatory evidence.","limitations":"This is a narrative review, not a systematic review or meta-analysis, so the evidence synthesis may not be comprehensive or unbiased. The abstract does not report specific efficacy numbers (e.g., reduction in monthly migraine days). Long-term safety data beyond the trial periods is limited. Reimbursement and cost remain significant barriers to clinical adoption. Real-world effectiveness may differ from clinical trial results."},{"rthcId":"RPEP-15886","title":"Evaluating the Impact of Glucagon-Like Peptide-1 Receptor Agonist Receptor Agonists on Postoperative Pain Management in Patients Undergoing Cancer Surgery: A Retrospective Study.","authors":"Pennycuff, Jenny E; Cortes-Mejia, Nicolas; Hernandez, Mike; Owolabi, Adebukola; Soliz, Jose; Cata, Juan P","year":2026,"journal":"Anesthesia and analgesia","doi":"10.1213/ANE.0000000000007967","pmid":"41698178","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15887","title":"SET-M33 peptide as a selective in vitro antimicrobial agent against the porcine respiratory pathogen Glaesserella parasuis.","authors":"Pereira Lourenço, Ana Laura; Rouam El Khatab, Oussama; Falciani, Chiara; Pini, Alessandro; Aragon, Virginia; Cerdà-Cuéllar, Marta; Kochanowski, Karl","year":2026,"journal":"Microbiology spectrum, e0391825","doi":"10.1128/spectrum.03918-25","pmid":"41705700","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15888","title":"Liposomal Encapsulation Reduces the Cytotoxic Effects of Gramicidin S in Monolayer and Spheroid Fibroblast Cultures.","authors":"Perepelytsia, Ihor; Bozhok, Galyna; Berest, Volodymyr; Gallo, Valentina; Pizzi, Marco; Sichevska, Larysa; Skorokhod, Oleksii","year":2026,"journal":"Antibiotics (Basel, Switzerland), 15(2)","doi":"10.3390/antibiotics15020177","pmid":"41750475","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15889","title":"Machine learning to optimize the diagnostic performance of natriuretic peptides for acute heart failure across age groups.","authors":"Perez Vicencio, Daniel; Doudesis, Dimitrios; Thurston, Alexander J F; Chenevier-Gobeaux, Camille; Claessens, Yann-Erick; Lopez Ayala, Pedro; Belkin, Maria; Wussler, Desiree; deFilippi, Christopher; Seliger, Stephen; Moe, Gordon; Fernando, Carlos; Bayes-Genis, Antoni; Pinto, Yigal; Gaggin, Hanna K; Wiemer, Jan C; Möckel, Martin; Rutten, Joost H W; Gargani, Luna; Pugliese, Nicola R; Pemberton, Christopher; Ibrahim, Irwani; Gegenhuber, Alfons; Mueller, Thomas; Neumaier, Michael; Behnes, Michael; Akin, Ibrahim; Bombelli, Michele; Grassi, Guido; Nazerian, Peiman; Albano, Giovanni; Bahrmann, Philipp; Richards, A Mark; McMurray, John J V; Mueller, Christian; Januzzi, James L; Mills, Nicholas L; Lee, Kuan Ken","year":2026,"journal":"ESC heart failure, 13(1)","doi":"10.1093/eschf/xvaf006","pmid":"41711701","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15890","title":"Harnessing pro-inflammatory and immunopathologic immune responses in urinary tract infections for vaccine development: it's all about a balance.","authors":"Periasamy, Sivakumar; Lübbers, Joyce; King, Susan; Hovingh, Elise S; van der Fits, Leslie; van den Dobbelsteen, Germie P J M","year":2026,"journal":"Frontiers in immunology, 17, 1753331","doi":"10.3389/fimmu.2026.1753331","pmid":"41705241","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15891","title":"Additive effect of leptin and palm-LEAP2(1-14) ameliorates obesity-induced metabolic stress in ob/ob mice.","authors":"Peteláková, Martina; Bouacha, Célia; Neprašová, Barbora; Sopko, Zuzana; Áčová, Andrea; Mráziková, Lucia; Kozák, Jaroslav; Zavřel, Martin; Cantel, Sonia; Fehrentz, Jean-Alain; Kuneš, Jaroslav; Železná, Blanka; Maletínská, Lenka","year":2026,"journal":"European journal of pharmacology, 1014, 178542","doi":"10.1016/j.ejphar.2026.178542","pmid":"41520761","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15892","title":"Recombinant AMPs (Epinecidin-1 and its Variants): A New Hope against Invasive Fungal Infections against Candida spp. and Aspergillus flavus.","authors":"Peter, Ansu Susan; Kandasamy, Indira; Ranjith, Sukumar; Jeyarajan, Sivakumar; Chidambaram, Prahalathan; Kumarasamy, Anbarasu","year":2026,"journal":"Current microbiology, 83(4), 168","doi":"10.1007/s00284-026-04770-z","pmid":"41665722","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15893","title":"The Impact of Semaglutide on Weight Loss and Inflammation in People with HIV. An Observational Prospective Study in Greek Population.","authors":"Petrakis, Vasileios; Rafailidis, Petros; Panopoulou, Maria; Konstantinidis, Theocharis; Tsantes, Andreas G; Babaka, Nikoleta; Papazoglou, Dimitrios; Panagopoulos, Periklis","year":2026,"journal":"Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association, 134(2), 29-35","doi":"10.1055/a-2737-6227","pmid":"41187787","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15894","title":"Tumor-induced orexigenic imbalance lowers protein appetite and drives early organ wasting symptoms.","authors":"Petsakou, Afroditi; Filine, Elizabeth; Li, Matthew; Chen, Yuchen; Zheng, Alice; Perrimon, Norbert","year":2026,"journal":"Nature communications","doi":"10.1038/s41467-026-70074-2","pmid":"41792134","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15895","title":"The interface between the homeostatic and hedonic energy balance circuitries in the regulation of appetitive behavior: A focus on steroidogenic factor-1/pituitary adenylate cyclase-activating polypeptide neurons in the hypothalamic ventromedial nucleus.","authors":"Phan, Christopher; Wagner, Edward J","year":2026,"journal":"Neuroscience, 592, 167-179","doi":"10.1016/j.neuroscience.2025.11.038","pmid":"41314528","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15896","title":"Clinical Considerations in the Use of Glucagon-Like Peptide-1 Receptor Agonists for Obesity Management.","authors":"Phan, Victoria; Bethune, Briana; Lathrop, Breanna","year":2026,"journal":"Nursing for women's health, 30(1), 61-67","doi":"10.1016/j.nwh.2025.09.003","pmid":"41453400","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15897","title":"Preparation and Characterization of Niosomes Containing Cationic Antimicrobial Peptides WSKK11 and WSRR11.","authors":"Phosri, Santi; Tastub, Sukanya; Kheawfu, Kantaporn; Intharuksa, Aekkhaluck; Daduang, Sakda; Maddocks, Sarah E; Theansungnoen, Tinnakorn","year":2026,"journal":"ACS omega, 11(5), 8446-8456","doi":"10.1021/acsomega.5c11221","pmid":"41696311","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15898","title":"The microbial tryptophan metabolite indole acts on the gastrointestinal tract to improve glucose homeostasis in a mouse model of diabetes by enhancing GLP-1 secretion and L cell differentiation.","authors":"Phuah, Phyllis; Norton, Mariana; Cheng, Sijing; Roberts, Anna G; Pirri, Daniela; Meyer, Leah; Chung, Pei-En; Dunsterville, Cecilia; Karwowski, Rafal; Lam, Brian Y H; Otsubo, Emile; Aleksashina, Sofia; Gribble, Fiona M; Reimann, Frank; Hanyaloglu, Aylin C; Yeo, Giles S H; Bewick, Gavin A; Jones, Ben; Owen, Bryn; Murphy, Kevin G","year":2026,"journal":"Diabetologia","doi":"10.1007/s00125-026-06688-4","pmid":"41776124","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15899","title":"Structural Optimization of Cn-AMP1 Enhances Antibacterial and Anticancer Potency With Low Hemolysis.","authors":"Phuong, Hai Bui Thi; Nguyen, Thanh Ngoc; Thi, Huyen Ha; Huang, Linyu; Tran, Phuong-Thao; Quoc, Thang Nguyen; Dao, Van-Duong; Bui, Le Minh; Xuan, Huy Luong","year":2026,"journal":"Biopolymers, 117(1), e70068","doi":"10.1002/bip.70068","pmid":"41334936","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15900","title":"Sex specific responses to oral vs. subcutaneous semaglutide in type 2 diabetes mellitus: A 12-month real-world study.","authors":"Piccione, Alessandra; Bonsangue, Maria; Barone, Martina; Vigneri, Enrica; Mineo, Mariagrazia Irene; Tomasello, Laura; Maniscalco, Laura; Pantò, Felicia; Arnaldi, Giorgio; Guarnotta, Valentina","year":2026,"journal":"Nutrition, metabolism, and cardiovascular diseases : NMCD, 36(3), 104462","doi":"10.1016/j.numecd.2025.104462","pmid":"41475990","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 212 type 2 diabetes patients (106 per group) followed for 12 months, subcutaneous semaglutide showed advantages over the oral formulation that differed by sex.\n\nIn men, the injectable form produced significantly greater reductions in weight (p=0.010), HbA1c (p=0.037), and LDL cholesterol (p=0.038) compared to oral semaglutide. In women, subcutaneous semaglutide led to significantly lower hepatic steatosis index (p=0.024) and greater reduction in GOT/AST liver enzyme levels (p=0.035) compared to men on the same treatment. Two hundred and eight of 212 patients completed the study (98% retention).","whyItMatters":"Semaglutide is one of the most widely prescribed GLP-1 receptor agonist peptides, but most clinical trials have not examined whether men and women respond differently to oral versus injectable formulations. This real-world evidence suggests that a one-size-fits-all approach may leave benefits on the table — men may gain more metabolic benefit from injections, while women may see particular liver health advantages. This supports the growing movement toward sex-aware, personalized diabetes management.","specificNumbers":"","methodology":"This was an interventional pilot study conducted in a real-world clinical setting. Two hundred and twelve patients with type 2 diabetes were equally assigned to receive either oral or subcutaneous semaglutide (106 per group). The primary endpoint was change in HbA1c (a measure of long-term blood sugar control). Secondary endpoints included changes in weight, lipid profiles, liver markers, and other metabolic parameters. All outcomes were analyzed for the overall cohort and then stratified by sex to detect differential responses.","limitations":"This is a pilot study with a relatively small sample size (212 patients). It was not randomized or blinded, which introduces potential selection bias. The study was conducted at a single center, limiting generalizability. The oral and subcutaneous formulations have different dosing regimens and bioavailability, which complicates direct comparison. Sex-stratified subgroup analyses reduce statistical power further. Longer follow-up would be needed to confirm durability of the observed differences."},{"rthcId":"RPEP-15901","title":"Thymic Neuroendocrine Tumors: Evolving Insights and Innovative Approaches.","authors":"Pietroluongo, Erica; Bestvina, Christine M; Brattin, Rachel; De Placido, Pietro; Di Lello, Anna; Haque, Waqas; Esposito, Alessandra; Bianco, Roberto; Choudhury, Noura; Garassino, Marina Chiara","year":2026,"journal":"JTO clinical and research reports, 7(2), 100935","doi":"10.1016/j.jtocrr.2025.100935","pmid":"41584722","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15902","title":"Design of Highly Potent Antibiofilm, Antimicrobial Peptides Using Explainable Artificial Intelligence.","authors":"Pikalyova, Karina; Akhmetshin, Tagir; Orlov, Alexey; Haney, Evan F; Akhoundsadegh, Noushin; You, Jiaying; Hancock, Robert E W; Horvath, Dragos; Marcou, Gilles Gérard; Cherkasov, Artem; Varnek, Alexandre","year":2026,"journal":"Journal of chemical information and modeling, 66(1), 744-755","doi":"10.1021/acs.jcim.5c01992","pmid":"41432371","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15903","title":"Epigenetic dysregulation of metabolic programs mediates liposarcoma cell plasticity.","authors":"Pimenta, Erica M; Garza, Amanda E; Camp, Sabrina Y; Park, Jihye; Hoffman, Samantha E; Valderrábano, Laura; Fu, Jingxin; Bi, Kevin; Carson, Maximilian T; Karam, Julie; Titchen, Breanna M; Medjahed, Sofia; Khandekar, Melin J; Shannon, Erin; Kang, Yun Jee; Coy, Shannon; Lin, Jia-Ren; Nag, Anwesha; Thorner, Aaron R; Gibson, William J; Santagata, Sandro; Raut, Chandrajit P; Hornick, Jason L; Merriam, Priscilla; Solimini, Nicole L; George, Suzanne; Demetri, George D; Van Allen, Eliezer M","year":2026,"journal":"Science translational medicine, 18(833), eadw4689","doi":"10.1126/scitranslmed.adw4689","pmid":"41564157","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15904","title":"Harnessing AI for Antimicrobial Peptide Innovation against Multidrug Resistance.","authors":"Pimentel, João P F; Quigua Orozco, Raquel M; de Rezende, Samilla Beatriz; Lima, Lucas; Cardoso, Marlon H","year":2026,"journal":"JACS Au, 6(2), 678-690","doi":"10.1021/jacsau.5c01520","pmid":"41755839","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15905","title":"Fixing the food environment: beyond weight-loss drugs.","authors":"Pineda, Elisa; Fenner, Charlotte; Middel, Cédric N H","year":2026,"journal":"Public health nutrition, 29(1), e43","doi":"10.1017/S1368980026101839","pmid":"41645430","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15906","title":"Repositioning GLP-1 Receptor Agonists in Endometrial Cancer: Molecular Rationale, Preclinical Insights, and Translational Opportunities.","authors":"Podder, Vivek; Coleman, Robert L; Hagemann, Andrea R; Singhania, Priya; Powell, Matthew A; Herzog, Thomas J; Slomovitz, Brian M","year":2026,"journal":"Clinical cancer research : an official journal of the American Association for Cancer Research, 32(3), 447-454","doi":"10.1158/1078-0432.CCR-25-2819","pmid":"41329840","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15907","title":"Antifungal activity of the antimicrobial peptide RP557 against priority fungal pathogens.","authors":"Poester, Vanice Rodrigues; Xavier, Melissa Orzechowski; Hidalgo, Jéssica Estefania Dávila; Dos Santos, Mônica Campos; Trápaga, Mariana Rodrigues; Al-Hatmi, Abdullah M S; Jaynes, Jesse; Stevens, David A","year":2026,"journal":"Microbiology (Reading, England), 172(3)","doi":"10.1099/mic.0.001663","pmid":"41770595","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15908","title":"Plasma Biomarkers Associated With Heart Failure Hospitalization Among Patients With Atrial Fibrillation and Subtypes of Heart Failure.","authors":"Pol, Tymon; Lindbäck, Johan; Oldgren, Jonas; Alexander, John H; Siegbahn, Agneta; Wallentin, Lars; Hijazi, Ziad","year":2026,"journal":"Journal of the American Heart Association, 15(2), e045970","doi":"10.1161/JAHA.125.045970","pmid":"41532553","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15909","title":"Quiet residents of the vaginal epithelium: immunohistochemical study on the distribution and role of human vaginal Merkel cells.","authors":"Polakovičová, Simona; Varga, Ivan; Filová, Barbora; Sallicandro, Luana; Voller, Jaroslav; Fioretti, Bernard; Krištúfková, Alexandra","year":2026,"journal":"BMC women's health","doi":"10.1186/s12905-026-04331-3","pmid":"41680777","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15910","title":"Insulinoma Unmasked By Tirzepatide: A Rare Case of Postprandial Hypoglycemia In a Nondiabetic Patient.","authors":"Polisky, Michael; Kamel, Dina; Ku, Jeong-Hee","year":2026,"journal":"JCEM case reports, 4(1), luaf290","doi":"10.1210/jcemcr/luaf290","pmid":"41356535","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tirzepatide use in a 63-year-old non-diabetic woman provoked severe postprandial hypoglycemia that led to the diagnosis of insulinoma. The incretin-based mechanism of tirzepatide (stimulating glucose-dependent insulin secretion via GLP-1 and GIP receptors) exacerbated the already excessive insulin production from the tumor, causing dangerously low blood sugar levels.\n\nThis case establishes that tirzepatide can unmask or worsen insulinoma-related hypoglycemia and highlights the need to include insulinoma in the differential diagnosis when patients on incretin-based therapies develop unexpected hypoglycemic episodes.","whyItMatters":"As millions of people start taking GLP-1/GIP receptor agonists for weight loss, rare but important drug-disease interactions will increasingly surface. Insulinomas affect about 1-4 per million people annually, but many go undiagnosed for years. With tirzepatide now being prescribed to a huge non-diabetic population, clinicians need to recognize that severe hypoglycemia in these patients may signal an underlying insulinoma rather than just a drug side effect. Early diagnosis of insulinoma is critical because it's typically curable with surgery.","specificNumbers":"","methodology":"Single patient case report documenting the clinical presentation, diagnostic workup, and outcomes of a 63-year-old non-diabetic woman who developed severe postprandial hypoglycemia after starting tirzepatide for weight management.","limitations":"Single case report — cannot establish the frequency of this interaction or predict which patients are at risk. The rarity of insulinoma means prospective studies would be extremely difficult. It's possible that the patient would have eventually been diagnosed without tirzepatide, though the drug clearly accelerated the presentation. The specific tirzepatide dose and timeline are not detailed in the abstract."},{"rthcId":"RPEP-15911","title":"Impact of Predischarge NT-proBNP on Treatment Optimisation in Acute Heart Failure.","authors":"Polovina, Marija; Tomić, Milenko; Janković, Milica; Civrić, Danka; Stojićević, Andrea; Stanković, Stefan; Pejović, Teodora; Viduljević, Mihajlo; Krljanac, Gordana; Ašanin, Milika; Stanković, Sanja; Seferović, Petar M","year":2026,"journal":"International journal of molecular sciences, 27(2)","doi":"10.3390/ijms27021028","pmid":"41596673","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Patients with a less than 30% reduction in NT-proBNP during hospitalization (ΔNT-proBNP < 30%) were discharged on significantly lower doses of guideline-directed medical therapy (GDMT) medications. This association was significant regardless of clinical characteristics or in-hospital management. The in-hospital NT-proBNP burden and trajectory, as markers of residual congestion, were directly associated with underutilization of recommended heart failure medications at discharge.","whyItMatters":"Residual congestion at hospital discharge is one of the strongest predictors of readmission and death in heart failure. Paradoxically, this study shows that the sickest patients — those with the most residual congestion — are discharged on the lowest doses of the medications proven to save their lives. Using NT-proBNP as a guide to treatment optimization before discharge could improve both medication use and patient outcomes.","specificNumbers":"","methodology":"Prospective observational study of patients hospitalized for acute heart failure with reduced ejection fraction (HFrEF). NT-proBNP levels were measured at admission and discharge. The percentage change in NT-proBNP (ΔNT-proBNP) was calculated and used to stratify patients. Discharge medication doses of titratable GDMT medications were compared across NT-proBNP trajectory groups.","limitations":"The abstract appears to be truncated and some statistical details are incomplete. The study design is observational, so it cannot determine whether lower NT-proBNP declines cause lower GDMT dosing or whether both reflect patient frailty and comorbidity burden. Specific sample sizes and complete outcome data are not available from the abstract. The study focused on HFrEF and may not apply to heart failure with preserved ejection fraction."},{"rthcId":"RPEP-15912","title":"GLP-1 receptor agonists: Bridging diabetes, obesity, and periodontitis-A scoping review of emerging evidence.","authors":"Polymeri, Angeliki; Feres, Magda; Giannobile, William V; Loos, Bruno G","year":2026,"journal":"Journal of periodontology","doi":"10.1002/jper.70092","pmid":"41711341","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15913","title":"Metabolic Dysfunction-Associated Steatotic Liver Disease and Peripheral Arterial Disease: Associations and Treatment Considerations.","authors":"Polyzos, Stergios A; Orfanidou, Myrsini; Kountouras, Jannis; Goulas, Antonis","year":2026,"journal":"Current vascular pharmacology","doi":"10.2174/0115701611414052251127074106","pmid":"41582340","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The literature review found that most clinical studies support an association between MASLD and PAD, particularly in the context of hepatic steatosis (fat accumulation in the liver). Evidence for associations with more advanced stages (steatohepatitis or fibrosis) is limited due to few biopsy-confirmed MASLD studies.\n\nManagement strategies for both conditions overlap significantly, centering on lifestyle modifications (diet, exercise, smoking cessation) and shared comorbidity management. Notably, GLP-1 receptor agonists and emerging dual and triple peptide agonists (investigated for MASLD) may provide cardiovascular benefits relevant to PAD. Established PAD medications like statins and aspirin may also benefit MASLD.","whyItMatters":"MASLD affects roughly 30% of the global population, and PAD affects over 200 million people worldwide. When they coexist, cardiovascular risk compounds significantly. The recognition that GLP-1 receptor agonists and newer multi-peptide agonists (like tirzepatide and retatrutide) could address both liver disease and vascular disease simultaneously represents a paradigm shift toward treating metabolic disease holistically rather than organ by organ.","specificNumbers":"","methodology":"The authors conducted a literature search of the PubMed database to identify clinical studies examining the association between MASLD and PAD. They critically appraised the evidence for this association and reviewed overlapping management strategies, with particular attention to pharmacological therapies that could benefit both conditions.","limitations":"This is a narrative review, not a systematic review or meta-analysis, so the literature search may not be comprehensive. Most evidence for the MASLD-PAD association comes from observational studies that cannot prove causation. Data on more advanced MASLD stages is scarce. No clinical trials have specifically evaluated medications for patients with both MASLD and PAD simultaneously. The potential benefits of GLP-1 agonists for PAD are largely extrapolated from cardiovascular outcome trials rather than PAD-specific studies."},{"rthcId":"RPEP-15914","title":"Review Article: The Evolving Role of GLP-1 Receptor Agonists in Gastroenterology Practice.","authors":"Pomenti, Sydney; Gerber, Annabel; Katzka, David; Camilleri, Michael; Hur, Chin","year":2026,"journal":"Alimentary pharmacology & therapeutics, 63(2), 203-209","doi":"10.1111/apt.70450","pmid":"41215723","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15915","title":"Risk stratification using coronary artery calcium and potential benefit of semaglutide therapy: A cost-effectiveness modelling study.","authors":"Ponnana, Sai Rahul; Zhang, Tong; Sirasapalli, Santosh Kumar; Chen, Zhuo; Dazard, Jean-Eudes; Surya, Niketh; Elhussain, Shamsa; Sivanantham, Kanimozhi; Okyere, Robert; Neeland, Ian J; Rajagopalan, Sanjay; Deo, Salil V","year":2026,"journal":"Diabetes, obesity & metabolism","doi":"10.1111/dom.70515","pmid":"41622983","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"People with coronary artery calcium scores of ≥400 had nearly double the risk of major cardiovascular events compared to those with scores of 0 (HR: 1.97). When modelling 3.3 years of semaglutide therapy, the number needed to treat to prevent one major cardiovascular event dropped from 151 for CAC=0 to just 34 for CAC≥400. The incremental cost-effectiveness ratio also improved dramatically: $625,863/QALY for CAC=0 versus $168,666/QALY for CAC≥400, though neither crossed the traditional willingness-to-pay threshold.","whyItMatters":"Semaglutide costs thousands of dollars per year, making it impractical to prescribe to every obese patient. This study provides a practical framework for using a simple, widely available test — coronary calcium scoring — to identify the patients who would get the most bang for the buck, potentially making the case for insurance coverage in high-risk groups.","specificNumbers":"","methodology":"The researchers used CAC scores from 38,058 participants in the CLARIFY registry who met SELECT trial criteria. Participants were stratified into four calcium score groups (0, 1-99, 100-399, ≥400). Multivariable Cox proportional hazard models estimated cardiovascular event risk across groups, and lifetime Markov models simulated semaglutide therapy outcomes to calculate number needed to treat and cost-effectiveness ratios.","limitations":"This is a modelling study, not a randomized trial, so the cost-effectiveness estimates depend on assumptions that may not hold in practice. The CLARIFY registry population may not be representative of all obese individuals. Even the best-case scenario (CAC≥400) still produced an ICER above the commonly used $100,000/QALY willingness-to-pay threshold. Real-world adherence and drug pricing changes could significantly alter results."},{"rthcId":"RPEP-15916","title":"Oral Semaglutide and Heart Failure Outcomes in Persons With Type 2 Diabetes: A Secondary Analysis of the SOUL Randomized Clinical Trial.","authors":"Pop-Busui, Rodica; Rasmussen, Søren; Deanfield, John E; Buse, John B; Marx, Nikolaus; Mulvagh, Sharon L; Inzucchi, Silvio E; Mann, Johannes F E; Emerson, Scott S; Poulter, Neil R; Engelmann, Mads D M; Hovingh, G Kees; Bayer Tanggaard, Katrine; Birkenfeld, Andreas L; Connelly, Kim A; Haluzik, Martin; Cavender, Matthew A; Kellerer, Monika; Jhund, Pardeep S; Gregersen, Søren; Nielsen, Olav Wendelboe; Lam, Carolyn S P; McGuire, Darren K","year":2026,"journal":"JAMA internal medicine","doi":"10.1001/jamainternmed.2025.7774","pmid":"41627802","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 9,650 participants with T2D and atherosclerotic CVD and/or CKD (median follow-up 47.5 months), 2,229 (23.1%) had heart failure at baseline. In participants with HF, oral semaglutide reduced the composite HF outcome (HF hospitalization, urgent HF visit, or CV death) by 22% (HR 0.78; 95% CI: 0.63-0.96). No significant benefit was seen in participants without HF (HR 1.01; 95% CI: 0.84-1.20).\n\nThe most striking subgroup result: patients with HF with preserved ejection fraction (HFpEF) showed a 41% reduction (HR 0.59; 95% CI: 0.39-0.86), while those with reduced ejection fraction (HFrEF) showed no significant benefit (HR 0.98; 95% CI: 0.70-1.38). MACE reduction with semaglutide was consistent regardless of HF status (HR 0.83 in HF; HR 0.86 in no HF). Serious adverse events were similar between semaglutide and placebo in the HF population.","whyItMatters":"Heart failure with preserved ejection fraction (HFpEF) affects millions and has been called the greatest unmet need in cardiovascular medicine — very few treatments have shown clear benefit. This analysis of the SOUL trial shows oral semaglutide reduces HFpEF events by 41%, which is among the largest treatment effects ever seen for this condition. Combined with the consistent MACE reduction, this positions oral semaglutide as potentially transformative for diabetic patients with heart failure.","specificNumbers":"","methodology":"Secondary analysis of the SOUL randomized clinical trial — a double-blind, placebo-controlled, event-driven phase 3b trial conducted at 444 centers in 33 countries. 9,650 participants with T2D and atherosclerotic CVD and/or CKD were randomized to once-daily oral semaglutide or placebo added to standard care. Participants were stratified by baseline HF status (2,229 with HF, 7,421 without). The prespecified composite HF outcome included time to first HF hospitalization, urgent HF visit, or cardiovascular death. Median follow-up was 47.5 months.","limitations":"This is a secondary (post-hoc) analysis of a trial not primarily designed to study heart failure outcomes. The HF subgroups, particularly HFpEF (n=991) and HFrEF (n=592), are relatively small for definitive subgroup conclusions. The interaction p-value for HF vs no-HF (p=0.06) did not reach conventional significance. The unknown HF subtype group (646 patients) complicates interpretation. Dedicated prospective trials in HFpEF populations would be needed to confirm these findings."},{"rthcId":"RPEP-15917","title":"Selective Interaction of the Antimicrobial Peptide RKW with Bacterial Lipid Bilayers: A Biophysical Approach.","authors":"Porritiello, Alessandra; Agrillo, Bruna; Gogliettino, Marta; Dardano, Principia; Miranda, Bruno; Adamo, Adele; Galatola, Emanuela; Balestrieri, Marco; Palmieri, Gianna","year":2026,"journal":"ACS omega, 11(7), 12281-12295","doi":"10.1021/acsomega.5c11601","pmid":"41768707","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15918","title":"Effect of Incretin-Based Weight Loss Drugs on Testosterone Concentrations in Men.","authors":"Portillo-Canales, Shellsea; Iqbal, Iqra; Akande, Rukayat; Ghimire, Allina; Kalishman, Amanda; Wood, Emily; Albert, Stewart G; Dhindsa, Sandeep","year":2026,"journal":"Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists","doi":"10.1016/j.eprac.2026.01.003","pmid":"41544705","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15919","title":"Real-world evaluation of clinical outcomes in Dutch patients with type 2 diabetes treated with oral semaglutide: A retrospective, observational cohort study using the PHARMO data network.","authors":"Postema, Abigail; Gaspersz, Jordy; Baak, Brenda N; Huisman, Eline L; Hoogstraten, Charlotte; Hagelund, Lise Meinicke; Penning-van Beest, Fernie J A; Overbeek, Jetty A","year":2026,"journal":"Diabetes, obesity & metabolism, 28(2), 895-905","doi":"10.1111/dom.70251","pmid":"41243611","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15920","title":"Acyl-CoA Synthetase 5 Knockout and Inhibitors Protect Against Diet-Induced Obesity in Mice by Activating the Ileal Brake.","authors":"Powell, David R; Van Sligtenhorst, Isaac; Main, Alan; Jin, Haihong; Carson, Kenneth G; Shi, Zhi-Cai; Swaffield, Jonathan; Smith, Melinda; Harris, Angela; Gopinathan, Suma; Platt, Kenneth A; Wade, Jeffrey; Zambrowicz, Brian; McDonald, Patricia; Orton, Darren; Kuttippurathu, Lakshmi; Mullens, Michael; Greer, Jennifer; Yang, Qi Melissa; Ding, Zhi-Ming","year":2026,"journal":"Journal of the Endocrine Society, 10(2), bvaf196","doi":"10.1210/jendso/bvaf196","pmid":"41623902","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15921","title":"Neoadjuvant Glucagon-Like Peptide-1 Receptor Agonists in Abdominal Wall Hernia Surgery: A Narrative Review.","authors":"Prabhakaran, Swetha; Wells, Oliver; Tsui, Lap Wah; Kong, Joseph Cherng Huei","year":2026,"journal":"World journal of surgery","doi":"10.1002/wjs.70260","pmid":"41653161","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Three retrospective studies showed that neoadjuvant GLP-1 receptor agonists in obese patients awaiting abdominal wall hernia repair:\n\n- Achieved significantly greater or equivalent weight loss and BMI reductions compared to conventional lifestyle modifications alone\n- Did not match pre-operative bariatric surgery in total weight loss and BMI reduction\n- Were associated with earlier surgery dates when weight loss was the barrier to proceeding, outperforming both lifestyle modifications and bariatric surgery timelines\n- Were not associated with increased post-operative complications or hernia recurrence rates\n\nThe review concludes there may be a promising role for GLP-1 drugs as a neoadjuvant bridge to surgery in obese hernia patients.","whyItMatters":"Obesity is both a cause of hernias and a major risk factor for surgical complications. Many surgeons delay hernia repair until patients lose weight, but conventional weight loss is slow and often unsuccessful. GLP-1 receptor agonists offer a pharmacological solution that could get patients to surgery faster and in better condition. This review provides the first evidence synthesis for this increasingly common clinical scenario, supporting a practical new use for these popular peptide drugs.","specificNumbers":"","methodology":"The authors conducted a narrative review with a computer-assisted search of Medline, PubMed, and EMBASE databases to identify studies reporting on GLP-1 receptor agonist use for pre-operative weight loss before abdominal wall hernia surgery. Three retrospective studies met inclusion criteria and were synthesized qualitatively.","limitations":"Only three retrospective studies were available, severely limiting the evidence base. There was significant heterogeneity among the included studies. No randomized controlled trials exist for this indication. Long-term outcomes (beyond immediate post-operative period) are unknown. The effects of GLP-1 drugs on wound healing, tissue quality, and muscle mass — all relevant to hernia repair — were not specifically addressed. Anesthesia-related concerns about GLP-1 drugs (delayed gastric emptying and aspiration risk) were not discussed in the abstract."},{"rthcId":"RPEP-15922","title":"HIV expression persists in the cerebrospinal fluid of HIV-associated neurocognitive disorders despite effective ART.","authors":"Prates, Gabriela S; Li, Xiaoyi; Folgosi, Victor; Shabangu, Ciniso S; Souza, George G; Apoliano, Carlos; Gascon, Maria R; Monteiro, Mariana A; Gualqui, Carolina; Santos Eichler, Rosangela; Gomes, Helio; Katuwal, Nikesh; Gilbert, Cassandra; Tang, Yuyang; Casseb, Jorge; Jiang, Guochun","year":2026,"journal":"Emerging microbes & infections, 15(1), 2616945","doi":"10.1080/22221751.2026.2616945","pmid":"41527791","tags":["hiv","biomarkers"],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"Despite effective antiretroviral therapy (ART) that suppressed HIV to undetectable levels in blood, HIV RNA and HIV-derived peptides (from Env and Pol proteins) were still detectable in the cerebrospinal fluid (CSF) of people with HIV-associated neurocognitive disorders (HAND). This was found even though ART drug concentrations in the CSF exceeded the levels needed to suppress active HIV replication.\n\nCritically, although HIV RNA and peptides were present in the CSF, the virus could not establish productive infection when tested in permissive immune cells — suggesting the brain harbors latently infected cells that express viral proteins without producing infectious virus. This non-replicative viral expression, rather than active infection, may drive the neuroinflammation and cognitive decline seen in HAND patients on ART.","whyItMatters":"Up to 50% of people with HIV develop some form of neurocognitive impairment even when their treatment successfully suppresses the virus in their blood. This study helps explain why: the brain acts as a viral reservoir where HIV can persist and produce inflammatory peptide fragments despite adequate drug levels. Understanding this mechanism is essential for developing therapies that can protect the brain — a challenge peptide-based and targeted drug delivery approaches may eventually help solve.","specificNumbers":"n=24 · 10 cognitively normal + 14 with HAND · HIV RNA undetectable in plasma but present in CSF · HIV-derived peptides (Env, Pol) found in HAND samples only · ART concentrations exceeded IC50 in CSF · No productive infection from CSF virus","methodology":"Cross-sectional study of 24 ART-treated people with HIV, stratified as cognitively normal (n=10) or having HAND (n=14, including ANI, MND, and HAD subtypes). Paired plasma and CSF samples were analyzed for HIV RNA (by RT-ddPCR), ART drug levels (by LC-MS/MS), and peptide profiles (by mass spectrometry peptidomics). Viral infectivity was assessed using viral outgrowth assays on permissive immune cells.","limitations":"Very small sample size (24 total, only 14 with HAND) limits statistical power and generalizability. Cross-sectional design cannot determine whether CSF viral persistence causes cognitive decline or is simply associated with it. The HAND subtypes (ANI=3, MND=9, HAD=2) had very small numbers for subgroup analysis. Peptidomic profiling identified HIV-derived peptides but could not quantify their levels precisely or determine their biological activity."},{"rthcId":"RPEP-15923","title":"The Potential of Non-Ribosomal Peptide Engineering for Creating New Antimicrobial Complexes.","authors":"Prazdnova, Evgeniya V; Kulikov, Maxim P; Khmelevtsova, Ludmila E","year":2026,"journal":"Molecules (Basel, Switzerland), 31(4)","doi":"10.3390/molecules31040683","pmid":"41752460","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15924","title":"Impact of chronic oxytocin on gaze and pupil dynamics during live dyadic interactions in children with autism.","authors":"Prinsen, Jellina; Daniels, Nicky; Moerkerke, Matthijs; Boets, Bart; Alaerts, Kaat","year":2026,"journal":"Psychoneuroendocrinology, 186, 107745","doi":"10.1016/j.psyneuen.2026.107745","pmid":"41547341","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15925","title":"Glucagon-like peptide-1 receptor agonists and muscle strength changes in older adults: Risks beyond muscle mass reductions.","authors":"Prokopidis, Konstantinos","year":2026,"journal":"British journal of pharmacology","doi":"10.1111/bph.70355","pmid":"41577337","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies a divergence between short-term and long-term findings:\n\nShort-to-mid-term trials (semaglutide, liraglutide in obesity):\n- Handgrip strength was statistically preserved despite reductions in lean soft tissue mass\n- Tirzepatide combined with resistance and aerobic training did not add strength benefits beyond exercise alone in young men\n\nLonger-term data (older adults with type 2 diabetes):\n- Longitudinal and retrospective studies reported reductions in handgrip strength with prolonged semaglutide use\n- Accelerated sarcopenia was observed\n- Potential detrimental effects on neuromuscular health\n\nKey insight: lean soft tissue loss is NOT a reliable predictor of muscle strength change following GLP-1/GIP agonist use — strength can be preserved despite mass loss (short-term) or decline despite what appears to be proportional mass loss (long-term).","whyItMatters":"Sarcopenia (age-related muscle loss) is already a major health problem in older adults, increasing the risk of falls, fractures, disability, and death. If GLP-1 drugs accelerate muscle strength decline in this population, the weight loss benefits could be offset by increased frailty. This is particularly concerning because older adults with type 2 diabetes — a primary target population for these drugs — are already at elevated sarcopenia risk. The review calls for monitoring muscle strength, not just weight and lean mass, in patients on these medications.","specificNumbers":"","methodology":"This is a narrative review summarizing emerging evidence from short-to-mid-term clinical trials, longitudinal studies, and retrospective research on GLP-1/GIP receptor agonists and muscle strength outcomes. The review compares findings across different drug types (semaglutide, liraglutide, tirzepatide), populations (younger adults with obesity vs. older adults with diabetes), and study durations.","limitations":"As a narrative review, this does not present original data or systematic methodology. The longer-term concerning findings come from retrospective and observational studies, which are prone to confounding. The definition and measurement of sarcopenia varies across studies. Handgrip strength is only one measure of muscle function and may not capture all relevant neuromuscular changes. The review does not distinguish between different GLP-1 drugs, doses, or treatment durations in detail. The role of concurrent exercise and nutrition is not consistently controlled across the cited studies."},{"rthcId":"RPEP-15926","title":"Oral Administration of Specific Bioactive Collagen Peptides in the Treatment of Moderate Forms of Atopic Dermatitis - A New Approach.","authors":"Proksch, Ehrhardt; Schunck, Michael; Zdzieblik, Denise; Oesser, Steffen","year":2026,"journal":"Skin pharmacology and physiology, 1-24","doi":"10.1159/000551215","pmid":"41758763","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15927","title":"Misrepresentation of semaglutide in social media.","authors":"Propfe, Lara Elisabeth; Seifert, Roland","year":2026,"journal":"Naunyn-Schmiedeberg's archives of pharmacology, 399(1), 815-832","doi":"10.1007/s00210-025-04403-5","pmid":"40682686","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15928","title":"Recombinant Expression and Antimicrobial Mechanism of Cysteine-Rich Antimicrobial Peptides from Tigriopus japonicus Genome.","authors":"Pu, Dan; Tao, Hongwei; Pang, Jingwei; Shi, Huishao; Wang, Junjian; Zhang, Wei","year":2026,"journal":"Marine drugs, 24(1)","doi":"10.3390/md24010045","pmid":"41590742","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15929","title":"Effect of glucagon-like peptide-1 receptor agonist on outcomes after elective total hip arthroplasty: A retrospective cohort study.","authors":"Puga, Troy; Box, McKenna W; Jen, Andrew; Liu, Yingxian; Riehl, John T","year":2026,"journal":"Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association","doi":"10.1016/j.jos.2026.02.002","pmid":"41735126","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15930","title":"Insulin resistance modulates gut microbiota and incretin response remodeling after bariatric surgery in severe obesity.","authors":"Puig, Rocío; Rodríguez-Peña, M-Mar; Hernández-Montoliu, Laura; Astiarraga, Brenno; Martínez, Eva; Balibrea, Jose M; Llauradó, Gemma; Tarascó, Jordi; Caballero, Albert; Joaquín, Clara; Puig-Domingo, Manel; Vilarrasa, Nuria; Fernández-Veledo, Sonia; Vendrell, Joan; Pellitero, Silvia","year":2026,"journal":"International journal of obesity (2005), 50(3), 568-578","doi":"10.1038/s41366-025-01971-7","pmid":"41520055","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"At 6 months post-sleeve gastrectomy, mean total weight loss was 26.5 ± 6% across both groups. Both high-IR and low-IR patients showed enhanced GLP-1 and GLP-2 secretion in response to meal tolerance testing after surgery.\n\nAt baseline, the high-IR group had higher relative abundance of Prevotella species (associated with adverse metabolic and inflammatory profiles). After surgery, the high-IR group experienced more pronounced microbiome changes: increases in Akkermansia and Veillonella species and decreases in Prevotella. Enhanced GLP-1 and GLP-2 responses correlated with weight loss and metabolic improvement, with this correlation being particularly strong in the low-IR group. These findings suggest insulin resistance status at baseline shapes both the microbiome remodeling and incretin peptide responses to surgery.","whyItMatters":"This study reveals that the metabolic benefits of bariatric surgery depend partly on how the gut microbiome and incretin peptide systems respond — and that response differs based on pre-existing insulin resistance. Understanding this interaction could help predict who will respond best to surgery and identify patients who might benefit from microbiome-targeted interventions (like probiotics or prebiotics) alongside surgery to optimize outcomes.","specificNumbers":"","methodology":"This was a prospective single-center study of 18 patients with severe obesity (mean BMI 45.03) and normal glucose tolerance who underwent sleeve gastrectomy. Patients were stratified by HOMA-IR index into high-IR (>95th percentile, n=9) and low-IR (<25th percentile, n=9) groups. Body composition, biochemistry, and gut microbiota were assessed before and 6 months after surgery. GLP-1 and GLP-2 responses were measured using a standardized meal tolerance test at both time points.","limitations":"The study had a very small sample size (9 per group), limiting statistical power and generalizability. Only sleeve gastrectomy was studied — results may differ with gastric bypass or other procedures. The 6-month follow-up may not capture long-term microbiome and incretin changes. All patients had normal glucose tolerance, so findings may not apply to those with diabetes. The correlation between GLP-1 responses and weight loss was stronger in the low-IR group, which needs explanation in larger studies."},{"rthcId":"RPEP-15931","title":"Plasma-Assisted KR-12 Conjugated PLGA Nanofibers With Dual Osteogenic and Biofilm-Inhibitory Activity.","authors":"Pulat, Günnur; Bilgiç, Eda; Sezer, Buse","year":2026,"journal":"Journal of biomedical materials research. Part A, 114(3), e70059","doi":"10.1002/jbm.a.70059","pmid":"41741969","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"KR-12-functionalized PLGA nanofiber scaffolds demonstrated dual functionality. For bone regeneration, human bone marrow mesenchymal stem cells on these scaffolds showed enhanced alkaline phosphatase (ALP) activity, increased calcium and collagen deposition, and upregulated expression of key bone markers: collagen type I (COL1), osteopontin (OPN), and osteocalcin (OCN), confirmed by immunofluorescence staining.\n\nFor infection prevention, the scaffolds potently inhibited biofilm formation by both multidrug-resistant (MRSA, P. aeruginosa) and non-MDR (E. coli, S. aureus) bacteria. The peptide was covalently conjugated to the nanofibers via cold atmospheric plasma (CAP) treatment — a novel approach for KR-12/PLGA combination not previously reported.","whyItMatters":"Implant-associated infections affect up to 5% of orthopedic procedures and are devastating when they occur — often requiring implant removal, prolonged antibiotic courses, and revision surgery. Biofilm formation on implant surfaces makes these infections nearly impossible to treat with systemic antibiotics. A scaffold that simultaneously fights infection and promotes bone growth eliminates the conflict between anti-infection treatment (which can impair bone healing) and bone regeneration (which can be disrupted by infection) — two goals that have traditionally worked against each other.","specificNumbers":"","methodology":"PLGA electrospun nanofibers were fabricated by electrospinning and surface-treated with cold atmospheric plasma to enable covalent KR-12 conjugation. Surface characterization used SEM, contact angle measurements, FITC labeling, and FTIR spectroscopy. Osteogenic activity was assessed by culturing human bone marrow-derived mesenchymal stem cells on the scaffolds and measuring ALP activity, calcium/collagen deposition, bone gene expression (COL1, OPN, OCN), and immunofluorescence. Antibacterial and anti-biofilm activity was tested against MDR MRSA and P. aeruginosa, and non-MDR E. coli and S. aureus.","limitations":"This is an in vitro study — the scaffolds have not been tested in animal bone defect models. The duration of antimicrobial activity from covalently bound KR-12 was not assessed long-term. The mechanical properties of the scaffolds and their suitability for load-bearing bone applications were not characterized. The cold atmospheric plasma treatment process may affect PLGA fiber properties. Clinical translation would require extensive in vivo testing, biocompatibility studies, and mechanical validation."},{"rthcId":"RPEP-15932","title":"Sweet stimuli induce cephalic phase insulin release to varying degrees in humans.","authors":"Pullicin, Alexa J; Lim, Juyun","year":2026,"journal":"Physiology & behavior, 303, 115123","doi":"10.1016/j.physbeh.2025.115123","pmid":"41067674","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Glucose and fructose elicited significant cephalic phase insulin and C-peptide release at 2 minutes. Sucralose did not produce a significant group-level response at 2 minutes but did elicit peak responses comparable to glucose and fructose. Individual variability in both timing and magnitude was substantial across all three stimuli.","whyItMatters":"Understanding how sweet taste alone triggers insulin release helps explain how the body prepares for food intake and has implications for artificial sweetener use, diabetes management, and appetite regulation.","specificNumbers":"N=28; 3 sessions per participant; glucose, fructose, and sucralose tested; C-peptide and insulin measured; significant at 2 min for glucose and fructose","methodology":"Crossover design with 28 healthy adults attending three sessions. Blood samples collected before and after oral stimulation with glucose, fructose, or sucralose. Plasma insulin and C-peptide measured to assess cephalic phase insulin release. Both group-level and individual-level analyses conducted.","limitations":"Small sample (N=28). Only healthy adults studied — diabetic patients may respond differently. Single exposure per sweetener. The abstract has apparent data truncation. Short-term acute responses only. Individual variability was very large, making group-level conclusions less reliable."},{"rthcId":"RPEP-15933","title":"Glucagon-like peptide-1 receptor agonist treatment reduces body weight and improves glycaemic outcomes in patients with concurrent overweight/obesity and type 1 diabetes: A systematic review and meta-analysis.","authors":"Purcell, Amanda R; Zhen, Xi May; Wong, Jencia; Glastras, Sarah J","year":2026,"journal":"Diabetes, obesity & metabolism, 28(1), 296-305","doi":"10.1111/dom.70188","pmid":"41334580","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15934","title":"Selective N-Terminal Modification of Peptides and Proteins Using Fatty Acyl Phosphates.","authors":"Pérez, Laura Rodríguez; King, Thomas A; Finnigan, William; Angelastro, Antonio; Cain, Kathleen M; Eldrid-Otterburn, Charles; Houghton, Jack W; Tate, Edward W; Barran, Perdita; Goundry, William R F; Flitsch, Sabine L","year":2026,"journal":"Angewandte Chemie (International ed. in English), 65(7), e13289","doi":"10.1002/anie.202513289","pmid":"41510599","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15935","title":"Semaglutide use is associated with neuromuscular junction degradation in older adults with type II diabetes mellitus.","authors":"Qaisar, Rizwan; Khan, Imran Ullah; Rehman, Atif Ur; Iqbal, M Shahid; Ahmad, Firdos; Karim, Asima","year":2026,"journal":"British journal of clinical pharmacology, 92(1), 149-161","doi":"10.1002/bcp.70253","pmid":"40855709","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15936","title":"Cell-Penetrating Peptide-Mediated siRNA Targeting of LDHC Suppresses Tumor Growth in a Triple-Negative Breast Cancer Zebrafish Xenograft Model.","authors":"Qasem, Hanan; Naik, Adviti; Gomez, Tricia; Ponraj, Janarthanan; Jafar, Umar; Sikhondze, Martin; Thomas, Remy; Mahmoud, Khaled A; Decock, Julie","year":2026,"journal":"Pharmaceutics, 18(1)","doi":"10.3390/pharmaceutics18010078","pmid":"41599186","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Four cell-penetrating peptides (R10, 10R-RGD, cRGD-10R, and iRGD-10R) were tested for delivering siRNA to silence LDHC in triple-negative breast cancer cells. Key results:\n\n- All CPP:siRNA complexes formed uniform nanocomplexes of 129-168 nm with low polydispersity\n- CPP-mediated siRNA delivery successfully silenced LDHC expression in TNBC cells\n- LDHC silencing inhibited tumor growth in zebrafish xenograft models\n- The approach showed a favorable safety profile with no significant toxicity\n- LDHC silencing also enhanced sensitivity to olaparib, a DNA damage response drug, in clonogenic assays\n\nThis represents the first proof-of-concept for CPP-mediated LDHC targeting as a cancer therapy strategy.","whyItMatters":"Triple-negative breast cancer has the fewest treatment options of any breast cancer subtype. LDHC is a particularly attractive target because it is almost exclusively expressed in tumor cells — not in normal tissues — which should minimize side effects. Cell-penetrating peptides offer a drug delivery solution for targets like LDHC where no small-molecule inhibitors exist. This combination of precise target and peptide-based delivery could open new therapeutic avenues for TNBC.","specificNumbers":"","methodology":"The researchers synthesized four CPP:siRNA nanocomplexes and characterized their physicochemical properties (size, uniformity). They tested delivery efficiency and gene-silencing activity in TNBC cell lines in vitro. Clonogenic assays assessed whether LDHC silencing improved sensitivity to olaparib. In vivo anti-tumor activity was evaluated using a TNBC zebrafish xenograft model, which allows rapid assessment of tumor growth and treatment safety.","limitations":"The in vivo testing was limited to zebrafish xenograft models, which are useful for rapid screening but don't fully replicate human tumor biology or drug metabolism. The abstract appears to have incomplete data (truncated results section). No mammalian in vivo models were used, and human clinical translation would require extensive additional testing. The long-term stability and efficacy of CPP:siRNA complexes in more complex biological environments remain unknown."},{"rthcId":"RPEP-15937","title":"Liraglutide improves cognitive function by reducing amyloid-beta peptide accumulation and inhibiting inflammation in 5 × FAD mice.","authors":"Qi, Liqin; Lin, Lijing; Zheng, Jiaping; Liu, Xiaoying; Liu, Xiaohong; Chen, Zhou; Liu, Libin","year":2026,"journal":"The journals of gerontology. Series A, Biological sciences and medical sciences, 81(2)","doi":"10.1093/gerona/glaf265","pmid":"41349262","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15938","title":"Neutrophil-initiated nociceptive ingrowth orchestrates inflammation resolution to potentiate bone regeneration.","authors":"Qi, Xuanyu; Yang, Guangzheng; Xu, Zeqian; Zhou, Mingliang; Liu, Tejing; Du, Jiahui; Lin, Sihan; Jiang, Xinquan","year":2026,"journal":"Bone research, 14(1), 9","doi":"10.1038/s41413-025-00481-6","pmid":"41554692","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15939","title":"Inhibition of P2X7R Activation Ameliorates Damage to the Corneas and Corneal Nerves of Rats with Streptozotocin (STZ)-Induced Type 1 Diabetes.","authors":"Qi, Yuanyuan; Guo, Qian; Li, Qi; Li, Wanting; Zhang, Wanjun; Zhao, Shaozhen","year":2026,"journal":"Current eye research, 51(2), 108-117","doi":"10.1080/02713683.2025.2563129","pmid":"41020362","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15940","title":"Integrated approaches to preventing macrovascular complications in type 2 diabetes mellitus: Advances in secondary prevention.","authors":"Qian, Fang; Dai, Jing; Huang, Qian","year":2026,"journal":"Pakistan journal of pharmaceutical sciences, 39(3), 684-699","doi":"10.36721/PJPS.2026.39.3.REG.15014.1","pmid":"41620898","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15941","title":"Heteropolymer ferritin nanocages as delivery vehicles for oral delivery of GLP-1 peptides.","authors":"Qian, Yiran; Chang, Xiaoxi; Sun, Mingyang; Chen, Yunqi; Zang, Jiachen; Lv, Chenyan; Zhao, Guanghua; Zhang, Tuo","year":2026,"journal":"Journal of colloid and interface science, 703(Pt 1), 139092","doi":"10.1016/j.jcis.2025.139092","pmid":"41005135","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Ferritin nanocages remained largely intact after 30 minutes of simulated gastric digestion and were highly resistant to intestinal proteolysis. In vivo, orally administered ferritin reached the intestinal tract without significant degradation. The GLP-1-ferritin fusion (HLG) was absorbed via TfR1-mediated endocytosis in Caco-2 monolayers. Oral HLG significantly reduced blood glucose levels and food intake in type 2 diabetic mice, while oral exenatide alone showed no such effects.","whyItMatters":"The holy grail of GLP-1 drug development is an effective oral formulation — avoiding the needles that many patients dislike. While oral semaglutide (Rybelsus) exists, it requires complex absorption enhancers and fasting. This ferritin-based approach offers a fundamentally different strategy: protect the peptide in a natural protein cage that the gut actively absorbs via existing receptor pathways. The complete failure of oral exenatide without the ferritin carrier dramatically demonstrates the technology's value.","specificNumbers":"","methodology":"Researchers engineered a fusion protein (HLG) linking GLP-1 to the C-terminus of heteropolymer ferritin. Gastrointestinal stability was tested through simulated digestion (gastric and intestinal). In vivo stability was confirmed by tracking orally administered ferritin in mice. Cellular absorption mechanisms were studied in Caco-2 intestinal cell monolayers. Efficacy was tested in type 2 diabetic mice, comparing oral HLG against oral exenatide.","limitations":"This is a preclinical mouse study. The diabetic mouse model may not predict human oral bioavailability. The fusion protein manufacturing complexity and scale-up feasibility were not addressed. Long-term safety of repeated oral ferritin nanocage administration is unknown. Comparison was against free exenatide, not against the engineered oral semaglutide formulation that uses absorption enhancers. Dosing relative to injectable GLP-1 drugs was not quantified."},{"rthcId":"RPEP-15942","title":"A novel peptide blocking CD93/IGFBP7 interaction normalizes tumor vessels and synergizes with radiotherapy for cancer immunotherapy.","authors":"Qian, Yuzhen; Zhang, Qiongqiong; Wu, Yahong; Sun, Yixuan; Cheng, Ying; Shi, Peishang; Wang, Qingchao; Qiu, Lu; Wang, Mingshuang; Zhao, Wenshan; Zhai, Wenjie; Li, Lingling","year":2026,"journal":"Pharmacological research, 225, 108118","doi":"10.1016/j.phrs.2026.108118","pmid":"41628738","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15943","title":"Revitalizing GIP: Therapeutic Potential in Metabolic and Neurodegenerative Disorders.","authors":"Qiao, Yingdan; Zhou, Fen; Mao, Tuohua; Gao, Ling","year":2026,"journal":"Diabetes, metabolic syndrome and obesity : targets and therapy, 19, 559587","doi":"10.2147/DMSO.S559587","pmid":"41710720","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15944","title":"Semaglutide ameliorates osteoarthritis progression through a weight loss-independent metabolic restoration mechanism.","authors":"Qin, Hongyu; Yu, Jiamin; Yu, Huan; Zhou, Chuqiao; Yuan, Dongfeng; Wang, Ziling; Zhu, Zhenglin; Wei, Guizheng; Ou, Peiyan; Li, Zhibin; Jiang, Hua; Shen, Jie; Xiao, Guozhi; Bai, Xiaochun; Wang, Huaiyu; Zhang, Huan-Tian; Speakman, John R; Chen, Di; Tong, Liping","year":2026,"journal":"Cell metabolism, 38(3), 582-597.e6","doi":"10.1016/j.cmet.2026.01.008","pmid":"41666927","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15945","title":"mRNA and Peptide Vaccines in Melanoma-Current Landscape and Future Direction.","authors":"Qin, Jiaxing Jason; Wang, Yang; Sandhu, Shahneen","year":2026,"journal":"Cells, 15(4)","doi":"10.3390/cells15040344","pmid":"41744786","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Synthetic long peptide (SLP) and mRNA vaccine platforms have demonstrated the ability to induce robust antigen-specific T-cell responses and modulate the tumor microenvironment in melanoma. Advances in next-generation sequencing and computational neoantigen prediction have enabled personalized vaccine design targeting patient-specific tumor mutations. These vaccines mechanistically synergize with immune checkpoint inhibitors, enhancing efficacy without adding systemic toxicity. The neoadjuvant (pre-surgical) setting is highlighted as particularly promising due to intact tumor antigens and draining lymphatic architecture for optimal immune priming.","whyItMatters":"Melanoma immunotherapy has been a major success story, but many patients still don't respond or eventually relapse. Peptide vaccines offer a way to make immunotherapy more effective by priming the immune system against specific tumor targets. The ability to personalize these vaccines to each patient's tumor mutations represents a shift toward truly precision cancer therapy.","specificNumbers":"","methodology":"This is a narrative review of the current clinical development landscape for mRNA and peptide vaccines in melanoma. The authors synthesize evidence from clinical trials, preclinical studies, and advances in neoantigen prediction technology to assess the state of the field and identify future directions.","limitations":"As a review article, this does not present new primary data. The field is still in relatively early clinical stages, and long-term efficacy and survival data from large randomized trials are limited. Manufacturing complexity and cost of personalized neoantigen vaccines remain challenges. The review focuses on melanoma, and findings may not generalize to all cancer types."},{"rthcId":"RPEP-15946","title":"Recapitulating tumor extracellular matrix alignment to decipher its role in eliciting malignant cell phenotypes using a peptide liquid crystal hydrogel.","authors":"Qin, Si-Yong; Cheng, Wei-Wei; Peng, Meng-Yun; Cai, Chuang; Lei, Qi; Huang, Rong; Cheng, Yin-Jia; Liu, Wen-Long; Ma, Yi-Han; Zhang, Ai-Qing; Wang, Lei","year":2026,"journal":"Biomaterials, 330, 124017","doi":"10.1016/j.biomaterials.2026.124017","pmid":"41581342","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15947","title":"A novel luteinizing hormone-releasing hormone (LHRH) receptor-targeting peptide LHRH-III': Design and application for targeted breast cancer therapy.","authors":"Qiu, Boxiang; Fan, Ruihua; Si, Guangxu; Wang, Jing; Wang, Kailun; Zheng, Guojun; Tian, Xinxin","year":2026,"journal":"European journal of medicinal chemistry, 305, 118563","doi":"10.1016/j.ejmech.2026.118563","pmid":"41518959","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15948","title":"Glucagon-like Peptide-1 Receptor Agonists and Risk of Pneumonia and Postprocedure Hospitalization Among Patients Undergoing Gastrointestinal Endoscopy.","authors":"Qiu, Chunyuan; Chen, Qiaoling; Tovar, Stephanie; Kwok, Karl; Hernandez Conte, Antonio T; Ferrara, Jammie T; Desai, Vimal; Shi, Jiaxiao M; Giap, Andrew Q; Wu, Bechien U","year":2026,"journal":"Gastro hep advances, 5(3), 100869","doi":"10.1016/j.gastha.2025.100869","pmid":"41660373","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In a propensity-matched cohort of 3,825 GLP-1RA users and 14,920 controls undergoing gastrointestinal endoscopy (63% colonoscopy, 25% EGD, 12% bidirectional):\n\n- Postprocedure pneumonia: 0.13% vs 0.25% (OR 0.56, 95% CI: 0.22-1.45) — no significant difference\n- 30-day postprocedural hospitalization: 1.9% vs 2.6% (OR 0.76, 95% CI: 0.59-0.98) — GLP-1 users actually had lower rates\n- No significant association with urgent care visits, emergency department visits, or 7- or 30-day mortality\n\nResults were adjusted for sedation type (conscious sedation vs. monitored anesthesia care) and study year. The findings held across procedure types.","whyItMatters":"This study directly addresses one of the most debated safety questions in anesthesiology and gastroenterology: should GLP-1 drugs be stopped before procedures requiring sedation? Many anesthesia guidelines have recommended holding GLP-1 drugs before surgery and endoscopy due to aspiration risk from delayed gastric emptying. This large real-world study provides the strongest evidence to date that uninterrupted GLP-1 therapy does not increase adverse events after sedated endoscopy, which could change clinical practice and reduce unnecessary medication interruptions.","specificNumbers":"","methodology":"This was a propensity-matched retrospective cohort study using data from January 2008 to June 2023. Patients with active GLP-1RA prescriptions at the time of GI endoscopy were matched 1:4 to non-GLP-1RA-exposed controls using propensity scores generated by logistic regression. Primary outcomes were postprocedural pneumonia and all-cause hospitalization, further adjusted for sedation type and study year. Secondary outcomes included urgent care visits, emergency department visits, and 30-day mortality.","limitations":"This is a retrospective observational study, which cannot definitively prove causation or exclude all confounders despite propensity matching. The study period (2008-2023) includes years when GLP-1 drug use was much less common, potentially affecting the representativeness of early patients. The specific GLP-1 drugs, doses, and duration of use before procedures were not differentiated. Gastric residual volumes were not measured, so the mechanism behind the safety findings is not established. The study focused on GI endoscopy specifically — results may not generalize to longer surgical procedures with deeper anesthesia."},{"rthcId":"RPEP-15949","title":"Antimicrobial peptide chensinin-1b attenuates T2DM progression in atherosclerotic ApoE-/- mice.","authors":"Qiu, Zhongpeng; Fan, Fan; Li, Zhenjia; Sun, Yue; Shang, Dejing","year":2026,"journal":"Diabetic medicine : a journal of the British Diabetic Association, e70232","doi":"10.1111/dme.70232","pmid":"41673947","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In ApoE-/- mice on a high-fat diet, atherosclerotic symptoms (inflammation, aortic plaques, elevated blood lipids) appeared at 6-10 weeks, while diabetes symptoms (elevated fasting blood glucose, pancreatic damage, insulin imbalance) emerged at 14 weeks — establishing that prolonged atherosclerosis precedes diabetes in this model. Chensinin-1b treatment alleviated progression of both atherosclerosis and type 2 diabetes, with the greatest benefit observed when treatment was initiated in the early stage of disease.","whyItMatters":"This study provides evidence for a direct link between atherosclerosis and subsequent diabetes development, and shows that a single peptide can address both conditions. The finding that early intervention is most effective supports the concept of preventing diabetes by treating cardiovascular disease early — a paradigm shift from treating these conditions separately.","specificNumbers":"","methodology":"ApoE-knockout mice were fed a high-fat diet to induce atherosclerosis. Disease progression was tracked at early (6 weeks), middle (10 weeks), and late (14 weeks) stages by measuring inflammatory markers, aortic plaque burden, blood lipids, fasting blood glucose, insulin levels, and pancreatic pathology. Chensinin-1b was administered at different disease stages to assess its anti-atherosclerotic and anti-diabetic effects.","limitations":"This is a mouse study using an artificial genetic model (ApoE-knockout), which may not fully represent the complex interplay between atherosclerosis and diabetes in humans. The high-fat diet model creates accelerated disease that differs from typical human disease progression. Dosing, pharmacokinetics, and safety of chensinin-1b in larger animals or humans are unknown. The mechanism by which this antimicrobial peptide exerts metabolic effects needs further clarification."},{"rthcId":"RPEP-15950","title":"An Integrated Strategy for the Discovery, Recombinant Expression, and Biological Evaluation of Anti-Inflammatory Peptides from Rice Protein.","authors":"Qu, Tingmin; Huang, Ruibo; Wu, Ying; Wu, Hao; Mu, Daichen; Duan, Yanting; Tan, Wenzhi; Huang, Qingming; Hu, Jian; Wen, Li","year":2026,"journal":"Journal of agricultural and food chemistry, 74(7), 6243-6255","doi":"10.1021/acs.jafc.5c15308","pmid":"41678382","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Three anti-inflammatory peptides (PHP1, GPA1, GPD1) were identified from rice protein using receptor-based screening. The lead peptide PHP1 was successfully produced via recombinant expression in E. coli at 28.5 ± 3 mg/L using a fusion tag system. PHP1 significantly reduced pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and nitric oxide in LPS-stimulated macrophages.\n\nMechanistically, PHP1 directly bound to NF-κB1 with a binding affinity of KD = 7.631 μmol/L and suppressed NF-κB1 phosphorylation — a key step in the inflammatory signaling cascade. The anti-inflammatory effect was validated in a mouse model of systemic inflammation.","whyItMatters":"Food-derived bioactive peptides are increasingly recognized as potential functional ingredients, but two barriers have limited their practical use: low natural abundance and high chemical synthesis costs. This study solves the production problem by showing that rice anti-inflammatory peptides can be efficiently manufactured using bacteria (E. coli), making large-scale production feasible. The identification of a specific molecular target (NF-κB1) elevates these from vaguely 'bioactive' to mechanistically characterized functional peptides.","specificNumbers":"3 anti-inflammatory peptides identified · 28.5 mg/L recombinant yield · KD = 7.631 μmol/L (PHP1-NF-κB1 binding) · TNF-α, IL-1β, IL-6 reduced · Mouse inflammation model validated","methodology":"Researchers used receptor-based computational screening to identify anti-inflammatory peptide candidates from rice protein. Three candidates were selected and the lead peptide (PHP1) was produced recombinantly in E. coli using a fusion tag expression system. Anti-inflammatory activity was tested in LPS-stimulated RAW264.7 macrophages measuring cytokine levels and nitric oxide. Binding to NF-κB1 was characterized by surface plasmon resonance. Efficacy was validated in a mouse model of systemic inflammation.","limitations":"The study focused primarily on one lead peptide (PHP1), and the other two candidates (GPA1, GPD1) were less characterized. The mouse model used systemic inflammation rather than specific disease conditions where these peptides might be applied. Oral bioavailability and stability of the peptides in the digestive tract were not addressed — critical factors for functional food application. Human studies are needed to confirm anti-inflammatory effects."},{"rthcId":"RPEP-15951","title":"N-terminal Pro-brain Natriuretic Peptide as a Prognostic Biomarker for Cardiac Surgeries: A Systematic Review.","authors":"Queiroz, Barbara Giovanna Souza Silva; Arruda, Andressa Maranhão de; Villa-Chan, Lara Maria Moura de Sá; Costa, Lays Sthefany Siqueira da; Monteiro, José Gildo de Moura; Santos, Ana Célia Oliveira Dos","year":2026,"journal":"Brazilian journal of cardiovascular surgery, 41(1)","doi":"10.21470/1678-9741-2024-0417","pmid":"41196806","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15952","title":"Intracellular Delivery of a p21-Derived Cell Cycle Inhibitory Peptide Using Elastin-like Polypeptides Suppresses Glioblastoma Cell Proliferation.","authors":"Quinn, Tiffany; Shaheen, Yumnaa; Raucher, Drazen","year":2026,"journal":"Molecules (Basel, Switzerland), 31(4)","doi":"10.3390/molecules31040597","pmid":"41752375","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15953","title":"Neurophysiological Effects of Dry Needling: A Systematic Review and Meta-analysis.","authors":"Rabanal-Rodríguez, Gabriel; Navarro-Santana, Marcos José; Valera-Calero, Juan Antonio; Gómez-Chiguano, Guido Fabián; Kocot-Kępska, Magdalena; Fernández-de-Las-Peñas, César; Plaza-Manzano, Gustavo","year":2026,"journal":"Archives of physical medicine and rehabilitation, 107(2), 299-314","doi":"10.1016/j.apmr.2025.08.019","pmid":"40921318","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15954","title":"Overscreening of patients on glucagon-like peptide-1 receptor agonists: A second \"epidemic\" of thyroid cancer overdiagnosis?","authors":"Raghunathan, Rajam; Jacobs, Anna; Gajic, Zoran; Castiglioni, Sofia; Dawood, Nardeen; Arthurs, Likolani; Ranjbar, Suedeh; Rothberger, Gary D; Seib, Carolyn D; Prescott, Jason; Allendorf, John; Liou, Rachel; Suh, Insoo; Patel, Kepal N","year":2026,"journal":"Surgery, 189, 109868","doi":"10.1016/j.surg.2025.109868","pmid":"41371825","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15955","title":"Targeting Neuropeptide Y: Novel Approaches to the Treatment of Cardiovascular and Haematological Disorders.","authors":"Rahangdale, Nikita D; Thombre, Kalyani R; Gupta, Krishna R; Umekar, Milind J","year":2026,"journal":"Cardiovascular & hematological disorders drug targets","doi":"10.2174/011871529X401261251128055509","pmid":"41588761","tags":[],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Neuropeptide Y (NPY), a 36-amino-acid peptide, plays a dual destructive role in cardiovascular and blood diseases when dysregulated. In the cardiovascular system, excessive NPY signaling through Y1 receptors promotes vasoconstriction, inflammation, atherosclerosis, heart failure, and hypertension. In blood disorders, NPY influences blood cell production (hematopoiesis), immune cell activity, and blood vessel formation, contributing to thrombosis and leukemia.\n\nThe review identifies multiple therapeutic strategies targeting NPY: receptor-specific agonists and antagonists (e.g., [Leu31,Pro34]NPY, BAY 53-6206), enzyme inhibitors (DPP4 and NEP inhibitors that affect NPY breakdown), and natural substances (flavonoids, polyphenols, saponins) that modulate NPY activity.","whyItMatters":"NPY is one of the most abundant neuropeptides in the body, yet its role in cardiovascular and blood diseases has been overlooked compared to its better-known functions in appetite and stress. This review connects the dots: the same peptide that controls your hunger and stress response also drives blood vessel constriction, inflammation, and abnormal blood cell behavior. Understanding NPY's receptor-specific effects (Y1 vs Y2 vs Y4 vs Y5) could enable targeted therapies that modulate harmful NPY signaling without disrupting its beneficial roles.","specificNumbers":"36 amino acids · 4 receptor subtypes (Y1, Y2, Y4, Y5) · Y1 activation → vasoconstriction/inflammation · multiple therapeutic approaches reviewed · DPP4 and NEP enzyme inhibitors identified · natural substance modulators cataloged","methodology":"Comprehensive literature review examining NPY-mediated mechanisms in cardiovascular diseases and hematological disorders. Covers NPY receptor pharmacology, signaling pathways, disease mechanisms, and therapeutic strategies including synthetic analogs, receptor-specific agents, enzyme inhibitors, and natural substances.","limitations":"Narrative review without systematic methodology. Most therapeutic approaches discussed are preclinical with limited clinical data. The complexity of NPY signaling across four receptor subtypes makes predicting clinical outcomes difficult. Natural substance modulators typically have weaker and less specific effects than synthetic agents. Therapeutic resistance is acknowledged but not deeply addressed."},{"rthcId":"RPEP-15956","title":"Smart Antibiofilm Platforms Based on Synthetic Antimicrobial Peptides-Engineered Hydrogels.","authors":"Rahela, Carpa; Agota-Katalin, Bogyor; Anca, Butiuc-Keul","year":2026,"journal":"Polymers, 18(4)","doi":"10.3390/polym18040471","pmid":"41754661","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15957","title":"Computational modelling the impact of GLP-1 receptor agonists on botulinum toxin A: Evidence for reduced treatment durability across neurologic and aesthetic indications.","authors":"Rahman, Eqram; Michon, Alain; Rao, Parinitha; Ahmed, Munim; Joseph, John H; Wu, Woffles Tl; Carruthers, Jean DA; Webb, William Richard","year":2026,"journal":"Toxicon : official journal of the International Society on Toxinology, 269, 108638","doi":"10.1016/j.toxicon.2025.108638","pmid":"41173332","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15958","title":"Disruptions in Aesthetic Medicine: A Global Analysis of GLP-1 Agonists Using Punctuated Equilibrium Framework.","authors":"Rahman, Eqram; Webb, William Richard; Sadeghi-Esfahlani, Shabnam; Rao, Parinitha; Garcia, Patricia E; Sayed, Karim; Ioannidis, Sotirios; Yu, Nanze; Nassif, Alexander D; Goodman, Greg J; Carruthers, Jean D A","year":2026,"journal":"Plastic and reconstructive surgery, 157(1), 84-102","doi":"10.1097/PRS.0000000000012307","pmid":"40690352","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15959","title":"Peptides for pain sensation and peptides for pain relief: Fighting fire with fire.","authors":"Rahman, Md Mahbubur; Shim, Ye Won; Kim, Yong Ho; Park, Chul-Kyu","year":2026,"journal":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 195, 118990","doi":"10.1016/j.biopha.2026.118990","pmid":"41518734","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15960","title":"Safety and effectiveness of tirzepatide during Ramadan fasting: Real-world evidence from patients with type 2 diabetes in Bangladesh.","authors":"Rahman, Muhammad Hafizur; Selim, Shahjada; Afsana, Faria; Hoque, Md Azizul; Saifuddin, M; Alam, Md Shah; Sharifuzzaman, Mirza; Hannan, Mohmmad Abdul; Hasan, Md Nazmul; Kamrul-Hasan, A B M; Mustari, Marufa; Ahammed, Afsar","year":2026,"journal":"Diabetes, obesity & metabolism, 28(2), 1508-1516","doi":"10.1111/dom.70343","pmid":"41342185","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15961","title":"Therapeutic Peptides in Orthopaedics: Applications, Challenges, and Future Directions.","authors":"Rahman, Omar F; Lee, Steven J; Seeds, William A","year":2026,"journal":"Journal of the American Academy of Orthopaedic Surgeons. Global research & reviews, 10(1)","doi":null,"pmid":"41490200","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15962","title":"Effect of intracerebroventricular (ICV) injection of antimicrobial peptide expressed in the body-2 (LEAP-2) and its interaction with cannabinoid and ghrelin systems on food intake in broiler chickens.","authors":"Rahmania, Ariana; Zendehdel, Morteza; Hassanpour, Shahin","year":2026,"journal":"Poultry science, 105(2), 106199","doi":"10.1016/j.psj.2025.106199","pmid":"41406822","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15963","title":"Review of design strategies for active targeted drug delivery systems for pancreatic cancer.","authors":"Rahmatulla, Aysha; Bi, Xiaoling; Wang, Ping; Wang, Xueni; Li, Shuangshuang; Zhang, Xinran; Qiao, Xiaofang; Chen, Yuzhou","year":2026,"journal":"European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 218, 114915","doi":"10.1016/j.ejpb.2025.114915","pmid":"41218726","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15964","title":"Association of GLP-1 Receptor Agonists with Post-Operative Outcomes after Achilles Tendon Repair in Obese Patients.","authors":"Rai, Carl; Woodrow, Jackson; O'Neill, Colin; Lee, Ivy; Ashkani-Esfahani, Soheil; Waryasz, Gregory","year":2026,"journal":"The Journal of foot and ankle surgery : official publication of the American College of Foot and Ankle Surgeons","doi":"10.1053/j.jfas.2026.02.007","pmid":"41690504","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15965","title":"C-X-C chemokine receptor type 4 (CXCR4) antagonism in precision oncology: Clinical applications and future directions.","authors":"Rajendran, Aswini; Elumalai, Veronica; Balasubramaniyam, Saranya; Elumalai, Karthikeyan","year":2026,"journal":"Cancer pathogenesis and therapy, 4(3), 208-218","doi":"10.1016/j.cpt.2025.08.003","pmid":"41732212","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15966","title":"D-Allulose Reduces Weight More Persistently than Oral Semaglutide While Both Equally Elevate Grip Strength in Diet-Induced Obese Mice.","authors":"Rakhat, Yermek; Banno, Seiya; Zhantleu, Dauren; Tsunekawa, Shin; Yabe, Daisuke; Seino, Yutaka; Iwasaki, Yusaku; Yada, Toshihiko","year":2026,"journal":"Nutrients, 18(4)","doi":"10.3390/nu18040707","pmid":"41754224","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In diet-induced obese mice under identical conditions:\n\n- Acute effects: D-allulose rapidly reduced feeding; oral semaglutide reduced it more slowly\n- Days 0-3: both profoundly reduced food intake and body weight equally\n- Days 4-10: weight loss diminished with oral semaglutide but was maintained with D-allulose\n- After treatment cessation: weight rebounded with semaglutide but was maintained with D-allulose\n- Both increased muscle grip strength equally\n- Mechanism: both activated anorexigenic (appetite-suppressing) leptin-responsive neurons in the hypothalamus, but only D-allulose significantly inhibited orexigenic (appetite-stimulating) ghrelin-responsive neurons\n- D-allulose works via both vagal afferent and central nervous routes; semaglutide mainly via central route","whyItMatters":"Weight regain after stopping GLP-1 drugs is a major clinical concern — most patients regain weight when they stop semaglutide. If D-allulose can maintain weight loss more sustainably (even if these are mouse results), it could complement or provide an alternative to expensive injectable drugs. The dual-pathway mechanism may explain why the effects are more durable.","specificNumbers":"","methodology":"Diet-induced obese mice received D-allulose or oral semaglutide under identical conditions: equivalent doses, oral gavage, and matched food/water deprivation. Acute food intake was measured, followed by sub-chronic assessment of food intake, body weight, and grip strength over 10 days. Hypothalamic neuron responses were studied to elucidate mechanistic differences between the two treatments.","limitations":"This was a short-term mouse study (10 days) that may not predict long-term human outcomes. D-allulose and oral semaglutide dosing equivalence in mice may not translate to human dosing. The oral gavage delivery method doesn't reflect normal eating behavior. Mouse appetite regulation differs from humans in important ways. The grip strength finding is preliminary and needs further investigation."},{"rthcId":"RPEP-15967","title":"Anti-adipogenic effect of cryptotanshinone in 3T3-L1 preadipocytes via binding to glucagon-like peptide 1 receptor and its signaling.","authors":"Rakib, Md Abdur; Kim, Yong-Sik","year":2026,"journal":"Phytomedicine : international journal of phytotherapy and phytopharmacology, 150, 157666","doi":"10.1016/j.phymed.2025.157666","pmid":"41380415","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15968","title":"Role of serine/threonine phosphatases 1 and 2A in pancreatic acinar fluid and electrolyte secretion.","authors":"Ramos-Álvarez, Irene; Mantey, Samuel A; Jensen, Robert T","year":2026,"journal":"American journal of physiology. Gastrointestinal and liver physiology, 330(2), G225-G241","doi":"10.1152/ajpgi.00304.2025","pmid":"41525767","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15969","title":"Cardiorenal safety and efficacy of angiotensin receptor-neprilysin inhibitors in heart failure across the ejection fraction spectrum: A meta-analysis and meta-regression of RCTs with 28,001 patients.","authors":"Rampengan, Derren D C H; Surya, Stevanus C; Tjandra, Kevin C; Lele, Juan A J M N; Rampengan, Starry H; Kadariswantiningsih, Ika N; Idrisov, Bulat; Idrisova, Alina; Empitu, Maulana A","year":2026,"journal":"Biomedical reports, 24(2), 23","doi":"10.3892/br.2025.2096","pmid":"41425656","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15970","title":"β-Hairpin Antimicrobial Peptides: Class Diversity and Sequence Analysis.","authors":"Ramtel, Rabina; Gu, Richard; Abdulkareem, Mutiat A; Randall, Justin R","year":2026,"journal":"ACS infectious diseases","doi":"10.1021/acsinfecdis.5c01055","pmid":"41622639","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15971","title":"Immunomodulatory Effects of the Antimicrobial Peptide KR-20: Implications for Trichomoniasis.","authors":"Ramírez-Ledesma, María G; Ávila, Eva E; Alva-Murillo, Nayeli","year":2026,"journal":"Molecules (Basel, Switzerland), 31(3)","doi":"10.3390/molecules31030413","pmid":"41683391","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15972","title":"Design, synthesis, molecular docking, and antimicrobial evaluation of hybrid peptides incorporating unnatural amino acids with enhanced hydrophobic sidechains.","authors":"Rao Marata, Subhash; Pawar, Tushar Janardan; Olivares-Romero, Jose Luis; Patel, Harun; Ahmad, Iqrar; Delgado-Alvarado, Enrique; Muteeb, Ghazala; Govindappa, Nagendra; Devi, Meghali; Kokate, Siddhant V; Basavegowda, Lakshmi","year":2026,"journal":"RSC advances, 16(12), 11090-11099","doi":"10.1039/d5ra05259a","pmid":"41757308","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15973","title":"A Case of Euglycemic Diabetic Ketoacidosis With Tirzepatide Use and Severe Calorie Restriction.","authors":"Raptis, Dimitrios; Theodoropoulos, Panagiotis; Shah, Mandar Kalpesh; Bloomgarden, Noah; Kishore, Preeti","year":2026,"journal":"JCEM case reports, 4(2), luaf324","doi":"10.1210/jcemcr/luaf324","pmid":"41613297","tags":["glp-1-receptor-agonists","safety"],"studyType":"case-report","evidenceStrength":"low","keyFinding":"A 30-year-old man with no known diabetes developed euglycemic diabetic ketoacidosis (EDKA) — a dangerous acid buildup in the blood without the expected high blood sugar — while taking tirzepatide for weight loss combined with intermittent fasting and a low-carbohydrate diet. The combination of a GLP-1/GIP receptor agonist with ketosis-inducing dietary restrictions created a perfect storm for this rare but serious complication.","whyItMatters":"As tirzepatide and other GLP-1 drugs become increasingly popular for weight loss, many users are combining them with aggressive dietary strategies like keto diets and intermittent fasting without medical supervision. This case warns that the combination can cause a life-threatening metabolic emergency — one that's especially dangerous because blood sugar stays normal, making it easy to miss.","specificNumbers":"1 patient · 30-year-old male · No prior diabetes diagnosis · Tirzepatide + intermittent fasting + low-carb diet","methodology":"Single case report describing the clinical presentation, diagnosis, and management of euglycemic diabetic ketoacidosis in a patient using tirzepatide alongside dietary interventions for weight loss.","limitations":"Single case report — cannot establish causation or determine how common this complication is. The relative contribution of tirzepatide versus the dietary restrictions versus possible undiagnosed diabetes is unclear. Case reports represent the lowest level of clinical evidence."},{"rthcId":"RPEP-15974","title":"Cancer Incidence Among Users of Glucagon-Like Peptide-1 Receptor Agonists.","authors":"Rashid, Zayed; Woldesenbet, Selamawit; Khalil, Mujtaba; Altaf, Abdullah; Zindani, Shahzaib; Mevawalla, Areesh; Sarfraz, Azza; Mumtaz, Khalid; Pawlik, Timothy M","year":2026,"journal":"Journal of general internal medicine","doi":"10.1007/s11606-026-10300-1","pmid":"41749007","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 106,088 patients (53,924 GLP-1RA, remainder insulin), 1,594 (1.9%) developed cancer. GLP-1RA use was associated with significantly lower risk of liver cancer (HR: 0.47, 95% CI: 0.27-0.82) and pancreatic cancer (HR: 0.23, 95% CI: 0.11-0.51) compared to insulin. Risk of all 14 other cancer types was comparable between groups (all p>0.05), including thyroid cancer — a historical concern with GLP-1 drugs.","whyItMatters":"With tens of millions of people taking GLP-1 drugs, cancer safety is a paramount concern. This is one of the largest studies to comprehensively evaluate cancer risk across 16 tumor types. Not only does it provide reassurance (no increased risk for any cancer type), but the strong protective signals for liver and pancreatic cancer — two cancers closely linked to diabetes and obesity — suggest GLP-1 drugs may have anticancer properties through mechanisms like reduced inflammation, improved insulin sensitivity, and weight loss.","specificNumbers":"","methodology":"Retrospective cohort study using IBM MarketScan database (2013-2021). 106,088 patients with type 2 diabetes were categorized into GLP-1RA and insulin groups. Overlap Propensity Score Weighting controlled for confounders. Cox proportional hazards models assessed risk for 16 cancer types. Mean age 51 years, 51.3% male.","limitations":"This is a retrospective observational study and cannot prove causation. The insulin comparison group may have more advanced diabetes, potentially confounding the results (protopathic bias). The follow-up period (2013-2021) may be too short for slow-growing cancers. Claims database data lacks clinical detail on cancer staging, BMI changes, and other confounders. Propensity score weighting reduces but cannot eliminate residual confounding. The impressive pancreatic cancer HR (0.23) should be interpreted cautiously given the small number of cases (n=87)."},{"rthcId":"RPEP-15975","title":"Diagnosis challenges and accessibility barriers to migraine management in Southeast Asia: results from the South-East Asia Local breAch on MigraiNe Treatment (SEALANT) study.","authors":"Rattanawong, Wanakorn; Hiransuthikul, Akarin; Anukoolwittaya, Prakit; Pongpitakmetha, Thanakit; Thanprasertsuk, Sekh; Manohararaj, Nijanth; Sulaiman, Wan Aliaa Wan; Saranza, Gerard; Wee, John Luis; Dayrit, Greg; Madjid, Irma Savitri; Sudibyo, Devi Ariani; Budianto, Pepi; Wu, Jr-Wei; Phoumindr, Appasone; Sirilertmekasakul, Chananchida; Tanprawate, Surat; Tepper, Stewart J","year":2026,"journal":"The journal of headache and pain, 27(1), 47","doi":"10.1186/s10194-026-02295-1","pmid":"41703442","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15976","title":"NPY2R Agonist-Induced Gastric Effects Leading to Intestinal Dysbiosis and Secondary Intestinal Pathology in CD1 Mice.","authors":"Rau, Sophie Ruth; Kalkuhl, Arno; van Esch, Eric; Hahn, Christian; Nolte, Thomas; Hempel, Katja","year":2026,"journal":"Toxicologic pathology, 54(2), 167-180","doi":"10.1177/01926233251392878","pmid":"41757733","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15977","title":"Effect of semaglutide on COVID-19 and other infections: an analysis from the FLOW randomized clinical trial.","authors":"Rayner, Brian; Mahaffey, Kenneth W; Mann, Johannes F E; Pratley, Richard E; Rossing, Peter; Belmar, Nicolas; Bosch-Traberg, Heidrun; Jeppesen, Ole Kleist; Tran, Minh Chau; Chernin, Gil; Tuttle, Katherine R","year":2026,"journal":"Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association","doi":"10.1093/ndt/gfag036","pmid":"41728915","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15978","title":"Synergistic role of exercise and liraglutide in modulating GLP-1R binding and metabolic outcomes: a combined computational and experimental study.","authors":"Razmi, Saeideh; Moshtaghie, Ali Asghar; Seyedabadi, Mohammad; Hashem, Nayeri; Akbarzadeh, Samad","year":2026,"journal":"3 Biotech, 16(3), 95","doi":"10.1007/s13205-025-04692-w","pmid":"41710474","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15979","title":"TRPM3 activation causes CGRP release in trigeminal neurons: Implications for migraine mechanisms.","authors":"Reducha, Philip V; Nielsen, Lukas K S; Jensen, Mette N; Edvinsson, Jacob C A; Kazantzi, Spyridoula; Wæver, Sofia L; Lylloff, Tanja; Westgate, Connar S J; Edvinsson, Lars; Haanes, Kristian A","year":2026,"journal":"Headache, 66(3), 672-687","doi":"10.1111/head.15082","pmid":"41133435","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"TRPM3 activation with the agonist CIM0216 (100 μM) triggered CGRP release from trigeminal ganglia, with indications of enhanced release in female tissues. Immunohistochemistry confirmed that TRPM3 and CGRP colocalize in trigeminal ganglion neurons, and TRPM3 was also detected in cerebral and meningeal arterial structures.\n\nCIM0216 application increased cytosolic calcium in CGRP-expressing trigeminal neurons in transgenic mice. However, subcutaneous CIM0216 did not induce allodynia-like symptoms in rats, suggesting TRPM3 activation alone may be insufficient to produce migraine-like pain behavior in vivo despite triggering CGRP release ex vivo.","whyItMatters":"Current migraine treatments target CGRP after it's already released. Identifying what triggers CGRP release upstream — in this case, the TRPM3 channel — opens the door to preventing CGRP release in the first place rather than just blocking its effects. TRPM3 could become a new drug target for migraine prevention, potentially complementing existing CGRP-targeting therapies.","specificNumbers":"","methodology":"Multi-modal preclinical study using male and female Sprague-Dawley rats and transgenic female mice. CGRP release from trigeminal ganglia and dura mater was measured by ELISA after CIM0216 stimulation. Myograph studies assessed vasodilation in cerebral and meningeal arteries. Immunohistochemistry examined TRPM3/CGRP colocalization in rat and human tissue. Mechanical sensitivity tests assessed behavioral responses. Calcium imaging was performed in transgenic mouse CGRP neurons.","limitations":"The TRPM3 agonist CIM0216 triggered CGRP release ex vivo but did not produce migraine-like pain behavior in vivo, raising questions about the physiological relevance of TRPM3 activation alone. The sex difference in CGRP release was indicated but not conclusively established. The study did not identify endogenous TRPM3 activators relevant to migraine triggers. Human dura mater was examined for expression but not for functional CGRP release."},{"rthcId":"RPEP-15980","title":"Nanoparticle-encapsulated neuropeptide Y provides robust seizure protection in SCN1A-derived epilepsy.","authors":"Reed, Samantha L; Aiani, Lauren M; Faiz, Eesha; Adediran, Emmanuel; Benveniste, Morris; Murnane, Kevin S; D'Souza, Martin; Escayg, Andrew; Wong, Jennifer C","year":2026,"journal":"Epilepsia, 67(1), 424-436","doi":"10.1111/epi.18649","pmid":"41074603","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Intranasal administration of nanoparticle-encapsulated NPY (NP-NPY) provided robust protection against 6 Hz-, pentylenetetrazole-, and hyperthermia-induced seizures in two mouse models of SCN1A-derived epilepsy. In Scn1a+/- mutant mice (a Dravet syndrome model), NP-NPY treatment reduced spontaneous seizure frequency.\n\nThe nanoparticle formulation overcomes a critical barrier in neuropeptide therapeutics: delivering a 36-amino-acid peptide to the brain through a non-invasive intranasal route, bypassing the blood-brain barrier without requiring surgery or gene therapy.","whyItMatters":"Dravet syndrome is a severe childhood epilepsy with high drug resistance — current medications often fail. NPY has been known to suppress seizures, but until now could only be delivered through invasive methods. This intranasal nanoparticle approach makes NPY brain delivery practical, potentially opening a new treatment avenue for one of the most devastating forms of childhood epilepsy.","specificNumbers":"","methodology":"Researchers developed a nanoparticle formulation to encapsulate NPY and administered it intranasally to mouse models of SCN1A-derived epilepsy. They tested seizure resistance using three different induction methods (6 Hz electrical stimulation, pentylenetetrazole chemical induction, and hyperthermia). They also monitored spontaneous seizures in Scn1a+/- Dravet syndrome model mice. Gene expression analysis compared NPY and NPY receptor levels in mutant and wild-type hippocampi.","limitations":"All experiments were in mice; human Dravet syndrome is more complex and variable. The duration of seizure protection after a single intranasal dose and the need for repeated dosing are not detailed. Long-term safety of intranasal nanoparticle administration to the brain needs assessment. The nanoparticle formulation's stability, shelf life, and manufacturing scalability are not discussed."},{"rthcId":"RPEP-15981","title":"Safety and Efficacy of Glucagon-Like Peptide-1 Receptor Agonists Use in Elderly People With Obesity-A Meta-Analysis.","authors":"Rego de Figueiredo, Inês; Simas, Filipa Sofia; Ghiletchi, Angela; Oliveira Torres, João; Silva-Nunes, José","year":2026,"journal":"Obesity (Silver Spring, Md.)","doi":"10.1002/oby.70098","pmid":"41640092","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15982","title":"Brain delivery of a neurotrophic peptide derived from secreted amyloid precursor protein APPsα as a therapeutic strategy for Alzheimer's disease.","authors":"Rehra, Lena; Erdinger, Susanne; Wagner, Lelia; Baltissen, Danny; Just, Jennifer; König, Leo; Mühlberg, Eric; Eisenzapf, Tom; Kilian, Lara; Banicevic, Marija; Bengelsdorff, Verena; Buchholz, Christian J; Mier, Walter; Uhl, Philipp; Korte, Martin; Fricker, Gert; Müller, Ulrike C","year":2026,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 389, 114374","doi":"10.1016/j.jconrel.2025.114374","pmid":"41187812","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15983","title":"The Emerging Implications of GLP-1 Receptor Agonists in Radiation Therapy.","authors":"Reinicke, Trenton; Dilworth, Joshua T","year":2026,"journal":"The oncologist","doi":"10.1093/oncolo/oyag073","pmid":"41776829","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15984","title":"Three stress-responsive peptides modulate immunity and development in the fall armyworm Spodoptera frugiperda.","authors":"Ren, Hai-Yan; Liu, Fang-Fang; Liang, Chao-Peng; Wen, Liang; Zhang, Bang-Xian; Rao, Xiang-Jun","year":2026,"journal":"Pesticide biochemistry and physiology, 216(Pt 1), 106798","doi":"10.1016/j.pestbp.2025.106798","pmid":"41326125","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15985","title":"Redox-Responsive Peptide Coacervates for Enhanced mRNA Delivery and Intracellular Release.","authors":"Ren, Shuling; Lin, Xinyu; Xie, Qijing; Yu, Siyuan; Zheng, Xiyu; Pan, Haifeng; Tan, Shanzhi; Wang, Yingbin; Zhang, Shiyin; Li, Tingdong; Ge, Shengxiang; Zhang, Jun; Xia, Ningshao","year":2026,"journal":"ACS nano, 20(1), 459-474","doi":"10.1021/acsnano.5c13501","pmid":"41451635","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15986","title":"Novel Angiotensin-Converting Enzyme Inhibitory Peptides from Bungarus multicinctus: Simulated Gastrointestinal Digestion, Identification and Antihypertensive Mechanism.","authors":"Ren, Yingying; He, Han; Cai, Yubin; Han, Shuyan; Ablat, Ayzohra; Yin, Qiang; Mu, Dandan","year":2026,"journal":"Pharmaceuticals (Basel, Switzerland), 19(1)","doi":"10.3390/ph19010096","pmid":"41599695","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15987","title":"A Biomimetic Norepinephrine-Loaded Aligned Mineralized Collagen Scaffold for Coordinated Neurovascular, Osteogenic, and Immunomodulatory Repair of Critical-Sized Bone Defects.","authors":"Ren, Zhengyun; Wu, Zhaojun; Wu, Anhang; Zhang, Hui; Lu, Jiachen; Zhang, Jiahao; Weng, Jie; Zhang, Jinhua; Chen, Song; Tan, Huan; Guo, Tailin","year":2026,"journal":"Advanced science (Weinheim, Baden-Wurttemberg, Germany), 13(8), e18807","doi":"10.1002/advs.202518807","pmid":"41271555","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The norepinephrine-loaded mineralized electrocompacted collagen scaffold (NE-MEC) promoted osteogenic differentiation of rat bone marrow mesenchymal stem cells while simultaneously upregulating nerve growth factor expression in early stages. This nerve growth factor activity supported peripheral nerve repair and induced production of calcitonin gene-related peptide (CGRP), which then enhanced both osteogenic differentiation and neovascularization.\n\nAdditionally, NE-MEC stimulated vascular endothelial growth factor A (VEGFA) expression in regenerating bone tissue and shifted macrophage polarization toward a pro-healing phenotype. Together, these effects created a regenerative feedback circuit coordinating bone, nerve, blood vessel, and immune repair in critical-sized bone defects.","whyItMatters":"Healing large bone defects is one of the most challenging problems in orthopedic medicine because successful repair requires simultaneous bone growth, nerve regeneration, blood vessel formation, and proper immune responses. Most biomaterials only address one or two of these processes. This scaffold creates an integrated feedback loop — driven in part by the peptide CGRP — that coordinates all four, potentially offering a more effective approach to treating severe fractures, tumor-related bone loss, and other critical-sized defects.","specificNumbers":"","methodology":"The researchers fabricated the scaffold using isoelectric focusing, mechanical stretching, and amorphous calcium phosphate mineralization to replicate the composition and aligned structure of natural bone, including the characteristic D-periodicity of collagen fibrils. Norepinephrine was incorporated into the scaffold for sustained release. The material was tested using rat bone marrow mesenchymal stem cells in vitro to assess osteogenic differentiation, nerve growth factor upregulation, CGRP production, VEGFA expression, and macrophage polarization.","limitations":"The study was conducted in rat models and cell cultures, so results may not directly translate to human bone repair. The abstract does not report specific quantitative outcomes such as bone volume measurements or statistical comparisons. Long-term safety and degradation behavior of the scaffold were not described. The norepinephrine release kinetics and optimal dosing for clinical application remain to be determined."},{"rthcId":"RPEP-15988","title":"Biofunctionalized 3D-printed gelatin-alginate scaffolds with arginine-glycine-aspartic acid (RGD) peptides for enhanced in vitro osteogenesis.","authors":"Renn, Ting-Yi; Ma, You-Ru; Hsu, Chia-Chen; Salamanca, Eisner; Egusa, Hiroshi; Sun, Ying-Sui; Lin, Chun-Pin; Chang, Wei-Jen","year":2026,"journal":"Journal of dental sciences, 21(1), 484-493","doi":"10.1016/j.jds.2025.10.030","pmid":"41585190","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15989","title":"Ambulatory blood pressure monitoring strengthens the cardiovascular signal of GLP-1RA: a meta-analysis of blood pressure and weight mediation.","authors":"Renna, Nicolás F; Ramirez, Eliel Ivan; Arrupe, Matias Fernando; Ramirez, Jesica Magalí","year":2026,"journal":"Journal of hypertension, 44(1), 123-129","doi":"10.1097/HJH.0000000000004158","pmid":"41230897","tags":["glp-1","cardiovascular"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"A meta-analysis of 21 randomized trials with 145,322 participants found that GLP-1 receptor agonists reduced major adverse cardiovascular events (MACE) by 14% (HR=0.86, 95% CI: 0.81–0.91). Both blood pressure reduction and weight loss independently contributed to this cardiovascular benefit.\n\nThe key insight: when blood pressure was measured using ambulatory monitoring (a 24-hour wearable device) rather than single office readings, the association between BP reduction and cardiovascular benefit was much stronger. This suggests that GLP-1 drugs' blood pressure effects may be underestimated by standard office BP measurements, and that BP lowering is a more important driver of their cardiovascular protection than previously appreciated.","whyItMatters":"There's been a debate about whether GLP-1 drugs protect the heart mainly through weight loss or through blood pressure reduction. This meta-analysis shows both matter independently, but that BP reduction may be a bigger contributor than we thought — we just weren't measuring it accurately enough. This supports using GLP-1 drugs specifically for hypertensive patients, including those with difficult-to-treat resistant hypertension.","specificNumbers":"21 RCTs · n=145,322 · HR=0.86 for MACE · 95% CI: 0.81–0.91 · SBP and weight independently associated with MACE reduction · Stronger BP signal with ambulatory monitoring","methodology":"Systematic review and meta-analysis of randomized controlled trials from January 2015 to April 2025 evaluating GLP-1RA or dual GLP-1/GIP agonists. Eligible trials reported MACE outcomes and changes in systolic blood pressure and/or weight. Random-effects meta-analyses pooled hazard ratios. Meta-regressions assessed whether BP and weight reductions mediated MACE reduction. Subgroup analyses compared trials using clinical BP versus ambulatory BP monitoring.","limitations":"Meta-regression can identify associations but cannot prove causation — the analysis cannot definitively determine what proportion of cardiovascular benefit comes from BP reduction versus weight loss versus other mechanisms. The subgroup analysis by BP measurement method depends on how individual trials measured BP, which varied. Individual patient data were not available, limiting the ability to control for all confounders."},{"rthcId":"RPEP-15990","title":"Streptococcus dentisani 7746 encodes a cocktail of 14 bacteriocins associated with Com and Blp-like quorum sensing regulatory systems.","authors":"Revilla-Guarinos, Ainhoa; Camelo Castillo, Anny; Cebrián, Rubén; Ferrer, María D; López-López, Arantxa; Adrados-Planell, Ana; Lahoz Oliva, Sandra; Ledesma, Laura; Hols, Pascal; Mira, Álex","year":2026,"journal":"Journal of oral microbiology, 18(1), 2633915","doi":"10.1080/20002297.2026.2633915","pmid":"41768604","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Genome mining with BAGEL4 and antiSMASH tools identified three new bacteriocin-coding genes in S. dentisani 7746, bringing its total to 14 — the largest bacteriocin repertoire known in any bacterial isolate. All 14 bacteriocins were confirmed to be transcriptionally expressed by RT-PCR.\n\nThe bacteriocins are regulated by complete sets of Com (competence) and Blp-like (bacteriocin-like peptide) quorum sensing systems. Eight previously unnamed bacteriocins were designated Denticins A through H. Analysis suggests that part of the Blp-like genomic region was acquired by horizontal gene transfer from pneumococci, explaining the unusually large repertoire.","whyItMatters":"Antimicrobial resistance is driving urgent demand for new antimicrobial agents. Bacteriocins — naturally produced antimicrobial peptides — are promising candidates because they specifically target competing bacteria without harming the host. Having a single probiotic strain that produces 14 different antimicrobial peptides creates a natural 'cocktail' approach that may be harder for pathogens to develop resistance against, with direct applications in oral health.","specificNumbers":"","methodology":"The closed genome of S. dentisani 7746 was analyzed using BAGEL4 and antiSMASH genome mining tools to identify bacteriocin biosynthetic gene clusters. Orthology conservation analyses distinguished between Blp and Com-related peptides. Non-quantitative cross-gene RT-PCR confirmed transcriptional expression of all identified bacteriocins.","limitations":"This study characterized bacteriocin genes and their transcription but did not assess the antimicrobial activity of each individual bacteriocin against specific oral pathogens. Transcription was confirmed qualitatively (non-quantitative RT-PCR), so relative expression levels are unknown. The functional significance of producing 14 bacteriocins versus fewer has not been experimentally tested. In vivo oral health benefits were not assessed."},{"rthcId":"RPEP-15991","title":"Hyperglycemia promotes maladaptive Dectin-1 signaling and impairs skin antifungal host defense.","authors":"Reyna, Dante E; Davis, Erin; Salina, Ana C G; Blackman, Amondrea; Martinez-Barricarte, Ruben; Doran, Amanda; Serezani, C Henrique","year":2026,"journal":"bioRxiv : the preprint server for biology","doi":"10.64898/2026.02.11.705431","pmid":"41726973","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15992","title":"Single vs. Dual Agonist Pharmacotherapy for Managing Insufficient Weight Loss and Weight Regain Following Metabolic and Bariatric Surgery: A Comparative Review.","authors":"Reytor-González, Claudia; Campuzano-Donoso, Martín; Sarno, Gerardo; Montalvan, Martha; Horowitz, Raquel; Rossetti, Gianluca; Pilone, Vincenzo; Barrea, Luigi; Muscogiuri, Giovanna; Schiavo, Luigi; Simancas-Racines, Daniel","year":2026,"journal":"Nutrients, 18(4)","doi":"10.3390/nu18040553","pmid":"41754068","tags":["glp-1-agonists"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"This comparative review found that single GLP-1 receptor agonists produce meaningful weight loss in patients who regain weight after bariatric surgery, while dual agonists targeting both GLP-1 and GIP receptors show even greater weight reduction in early studies.\n\nHowever, the review emphasizes that post-surgical patients face unique challenges — including higher risk of micronutrient deficiencies, gastrointestinal intolerance, and maladaptive eating patterns — that require pharmacotherapy to be integrated with nutritional counseling, psychological support, and long-term multidisciplinary care.","whyItMatters":"Weight regain after bariatric surgery is a common and frustrating problem, affecting a significant portion of patients. This review maps out how newer peptide-based drugs — especially dual agonists like tirzepatide — could fill an important treatment gap, giving surgeons and patients a pharmacological safety net when surgery alone isn't enough.","specificNumbers":"","methodology":"Comparative narrative review of published studies on single (GLP-1 receptor agonist) and dual (GLP-1/GIP receptor agonist) pharmacotherapies in post-bariatric surgery patients experiencing insufficient weight loss or weight regain.","limitations":"This is a narrative review, not a systematic review or meta-analysis, so the evidence synthesis is qualitative rather than quantitative. The review notes that dedicated head-to-head clinical trials comparing single vs. dual agonists specifically in post-bariatric populations are still lacking."},{"rthcId":"RPEP-15993","title":"Isolation, characterization, and genomic analysis of Bacillus halotolerans C1 as a robust alkaline protease source.","authors":"Rezvani, Maryam; Soorni, Aboozar; Sedghi, Mohammad","year":2026,"journal":"3 Biotech, 16(1), 18","doi":"10.1007/s13205-025-04661-3","pmid":"41376883","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15994","title":"Autonomic neural control of motor activity in the intestine of freshwater barramundi (Lates calcarifer).","authors":"Rhodes, Hayley; Travis, Lee; Hibberd, Timothy J; Spencer, Nick J; Harris, James","year":2026,"journal":"Cell and tissue research, 403(1), 10","doi":"10.1007/s00441-025-04034-5","pmid":"41557056","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15995","title":"XCPP: A Multi-model Explainable Deep Learning Framework for Accurate Identification of Cell-Penetrating Peptides from Structured Sequence Features.","authors":"Riasat, Hafsah; Alkhalifah, Tamim; Alturise, Fahad; Khan, Yaser Daanial","year":2026,"journal":"Current drug targets","doi":"10.2174/0113894501416864251212082231","pmid":"41588770","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15996","title":"From Structure to Function: Development of Relaxin-3 Analogs and their Role in RXFP3 Signaling.","authors":"Riches, Isabelle; Wu, Hongkang; Kalaba, Predrag; Sethi, Ashish; Lkhagvajargal, Tim; Ryan, Philip J; Maslov, Ivan; Bathgate, Ross A D; Hossain, Mohammed Akhter","year":2026,"journal":"Chembiochem : a European journal of chemical biology, 27(1), e202500664","doi":"10.1002/cbic.202500664","pmid":"41204779","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15997","title":"Obesity and asthma: obesity causes and aggravates asthma across the entire type-2 inflammation spectrum.","authors":"Riemann, Sebastian; Matthys, Imke; Maes, Tania; Lapauw, Bruno; Brusselle, Guy","year":2026,"journal":"The European respiratory journal","doi":"10.1183/13993003.02687-2025","pmid":"41713950","tags":[],"studyType":"Review","evidenceStrength":"strong","keyFinding":"Obesity increases the risk of developing asthma by 30-50% and is one of the most common comorbidities in people with established asthma, with up to 70% of adult asthma patients being overweight or obese. The review challenges the simplistic view that obesity-related asthma is only a \"Type-2-low\" phenotype, showing instead that excess fat affects asthma across the entire inflammatory spectrum through multiple mechanisms including dysregulated adipokine signaling, systemic inflammation, metabolic dysfunction, and mechanical compression of the lungs.\n\nCritically for the peptide field, the authors call for randomized, placebo-controlled trials of GLP-1 and dual GLP-1/GIP agonist therapies specifically in asthma patients with obesity. Weight reduction — whether through lifestyle changes, drugs, or bariatric surgery — improves asthma symptoms, lung function, and exacerbation risk regardless of the inflammatory subtype. Patients with obesity respond similarly to anti-T2 biologics for reducing exacerbations as lean patients, though symptom and lung function improvements are more variable.","whyItMatters":"With GLP-1 agonists driving unprecedented weight loss in clinical practice, this review makes the case that these peptide drugs could become important tools for managing asthma — not by targeting the lungs directly, but by reducing obesity-driven inflammation and mechanical burden. The explicit call for GLP-1/GIP agonist trials in asthma signals a major potential expansion of the peptide therapeutic landscape.","specificNumbers":"650M+ adults with obesity globally · 30-50% higher asthma risk · Up to 70% of asthma patients overweight/obese · Mean BMI in asthma trials: 28-30 kg/m²","methodology":"Narrative review published in the European Respiratory Journal synthesizing evidence on the epidemiology, pathophysiology, and treatment of obesity-associated asthma, with specific attention to the role of weight reduction therapies including GLP-1 agonists.","limitations":"As a narrative review, it reflects expert synthesis rather than systematic methodology. The call for GLP-1 trials in asthma is based on extrapolation from weight loss data rather than direct evidence. The heterogeneity of obesity-related asthma phenotypes means treatment effects may vary substantially between individuals."},{"rthcId":"RPEP-15998","title":"Supramolecular coiled-coil peptide platform for site-specific antibody drug conjugate engineering.","authors":"Ringaci, Alina; Shih, Ting-Yu; Grinstaff, Mark W","year":2026,"journal":"Nature communications","doi":"10.1038/s41467-026-70094-y","pmid":"41771920","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-15999","title":"Real-World Effectiveness of Insulin Glargine 300 U/ml in People with Type 2 Diabetes Previously Treated with Tirzepatide: The DELIVER-T Study.","authors":"Ritzel, Robert; Davies, Melanie J; Hao, Lichen; Ji, Linong; Mk, Lintu; Mabunay, Aileen; Mauricio, Didac; Bailey, Timothy","year":2026,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders, 17(1), 133-147","doi":"10.1007/s13300-025-01798-5","pmid":"41269514","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16000","title":"Peptide-Guided Photodynamic Therapy via Integrin αvβ6 in Pancreatic Cancer.","authors":"Roberto, Miriam; La Cava, Francesca; Arena, Francesca; Cordaro, Alessia; Stummo, Francesco; Cabella, Claudia; Stefania, Rachele; D'Andrea, Luca D; Blasi, Francesco; Terreno, Enzo; Reitano, Erika","year":2026,"journal":"International journal of molecular sciences, 27(4)","doi":"10.3390/ijms27041838","pmid":"41751975","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16001","title":"Obesity and Female Reproductive Health; Is There a Role for Glucagon-Like Peptide-1 Receptor Agonists?","authors":"Roberts, Rachel; Markande, Anurag; Kasaven, Lorraine; Williams, Sarah Chieveley; Faris, Raef; Bracewell-Milnes, Timothy; Thum, Yau; Nicopoullos, James; Jones, Benjamin P","year":2026,"journal":"Obesity reviews : an official journal of the International Association for the Study of Obesity, 27(2), e70015","doi":"10.1111/obr.70015","pmid":"41077659","tags":["glp-1-agonists","obesity","female-fertility"],"studyType":"review","evidenceStrength":"review-narrative","keyFinding":"This review examines whether GLP-1 receptor agonists could help women with obesity improve their fertility by enabling rapid preconception weight loss. Women with elevated BMI take longer to conceive and have poorer outcomes from fertility treatments, and many clinics require a BMI under 30 before starting IVF. GLP-1 drugs offer faster weight loss than diet and exercise alone, and may also reverse some of the metabolic dysfunction associated with obesity and polycystic ovarian syndrome (PCOS) — both of which impair fertility.\n\nThe review finds this is an emerging but promising area: GLP-1 agonists could help women reach treatment-eligible weight faster, which matters because reproductive potential declines with age. However, the authors note significant gaps in safety data regarding preconception use and highlight ethical considerations around prescribing these drugs specifically for fertility access.","whyItMatters":"Many women with obesity face a double bind: they need to lose weight to access fertility treatment, but the time spent losing weight reduces their remaining fertile years. If GLP-1 drugs can safely accelerate preconception weight loss while also improving the metabolic conditions (like insulin resistance in PCOS) that impair fertility, they could transform reproductive care for overweight women.","specificNumbers":"BMI ≥30 threshold commonly required by fertility clinics · Obesity associated with longer time to conception · PCOS affects metabolic and reproductive function","methodology":"Narrative review summarizing existing literature on obesity's effects on female fertility, the pharmacology of GLP-1 receptor agonists, and emerging evidence for their use in improving fertility outcomes in women with obesity and PCOS.","limitations":"This is a narrative review, not a systematic review or meta-analysis. It synthesizes existing knowledge rather than presenting new data. The evidence for GLP-1 agonists specifically improving fertility outcomes is still limited and emerging. Safety data for preconception GLP-1 use are lacking, and the required washout period before conception adds complexity."},{"rthcId":"RPEP-16002","title":"Metabolic Outcomes in Patients With Type 2 Diabetes Prescribed Incretin-Based Therapy and Referred or Not to a Weight Management Clinic: A Single-Center Retrospective Analyses.","authors":"Robinson, Kathleen M; Rodriguez, Stephanie H; Pedagarla, Cyril; Eyck, Patrick Ten; Correia, Marcelo; Dokun, Ayotunde","year":2026,"journal":"Obesity science & practice, 12(1), e70114","doi":"10.1002/osp4.70114","pmid":"41531807","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16003","title":"Structural insights, immunomodulatory functions, and therapeutic potential of host defense peptides in avoiding antimicrobial resistance.","authors":"Rodrigues, Gisele Regina; Leite, Michel Lopes; Franco, Octavio Luiz","year":2026,"journal":"Advances in protein chemistry and structural biology, 149, 313-332","doi":"10.1016/bs.apcsb.2025.08.001","pmid":"41581935","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16004","title":"Presentation of hemagglutinin on adjuvant-bearing self-assembling peptide nanofibers increases heterologous responses against influenza.","authors":"Roe, Emily F; Votaw, Nicole L; Lazar, Kat M; Burke, Kaitlyn N; Miranda, Hector A; Fries, Chelsea N; Rock, Michelle L; Macintyre, Andrew N; Stover, Erica L; Huskey, Jessica B; Harris, Summer J; Landon, Chelsea D; Mansouri, Katayoun; Edwards, Robert J; Heaton, Nicholas S; Collier, Joel H","year":2026,"journal":"Acta biomaterialia, 209, 211-224","doi":"10.1016/j.actbio.2025.11.025","pmid":"41265773","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Two methods of conjugating hemagglutinin (HA) to Q11 peptide nanofibers were demonstrated:\n\n1. β-tail co-assembly: Produced increased antibody responses; with KEYA adjuvant, achieved modest increases in antibody breadth and survival against flu challenge\n\n2. SortaseA (SrtA)-mediated ligation: Superior results — augmented antibody responses, significantly increased breadth of antibody binding to HA trimers spanning up to 30 years of antigenic drift from the immunizing antigen, increased hemagglutination inhibition to both homologous and heterologous viruses, and protected against lethal influenza challenge\n\nThe KEYA peptide adjuvant (random combinations of lysine, glutamic acid, tyrosine, and alanine) provided non-reactogenic immune enhancement without disrupting HA antigenicity at low concentrations.","whyItMatters":"Influenza kills hundreds of thousands of people annually, and the need for yearly vaccine reformulation is a major public health challenge. A vaccine platform that generates broadly protective antibodies against decades of viral evolution could dramatically reduce the burden of seasonal flu and improve pandemic preparedness. Self-assembling peptide nanofibers offer a modular, scalable platform that is non-reactogenic (fewer side effects) and can be adapted to display different antigens — potentially for other pathogens as well.","specificNumbers":"","methodology":"Researchers conjugated influenza hemagglutinin to Q11 self-assembling peptide nanofibers using two methods: β-tail co-assembly and SortaseA-mediated enzymatic ligation. The KEYA polypeptide adjuvant was incorporated into nanofiber formulations at varying concentrations. HA antigenicity was verified after conjugation. Mice were immunized and immune responses assessed by ELISA (antibody binding breadth to HA trimers from different flu variants spanning decades), hemagglutination inhibition assays (functional antibody activity), and lethal influenza challenge experiments (survival).","limitations":"All experiments were conducted in mice, whose immune responses differ from humans. The 30-year antibody breadth was measured by binding assays, which may not perfectly predict protection against live virus in humans. Durability of the immune response beyond the study period is unknown. Manufacturing scalability and cost of SortaseA-mediated conjugation at commercial scale need evaluation. The study used a single HA subtype; performance against other influenza subtypes (e.g., H3N2, influenza B) was not tested."},{"rthcId":"RPEP-16005","title":"SARS-CoV-2 fusion-peptide-directed antibodies are elicited by natural infection and can mediate broad sarbecovirus neutralization.","authors":"Roederer, Alex L; Li, Chia Jung; Lim, Eunice; Cao, Yi; Ronsard, Larance; Lingwood, Daniel; Canaday, David H; Gravenstein, Stefan; Balazs, Alejandro B","year":2026,"journal":"Cell reports, 45(2), 116954","doi":"10.1016/j.celrep.2026.116954","pmid":"41632570","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16006","title":"Long-acting GIPR agonist LY3537021 reduces body weight and fasting blood glucose in patients with T2D: Preclinical development and phase 1 randomized ascending dose studies.","authors":"Roell, William; Alsina-Fernandez, Jorge; Qu, Hongchang; Coskun, Tamer; Benson, Charles; Haupt, Axel; Kelly, Ronan P; O'Farrell, Libbey; Sloop, Kyle W; Steele, James P; Ficorilli, James; Regmi, Ajit; Rettiganti, Mallikarjuna; Urva, Shweta; Mather, Kieren J; Pratt, Edward","year":2026,"journal":"Molecular metabolism, 103, 102298","doi":"10.1016/j.molmet.2025.102298","pmid":"41391569","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16007","title":"Efavirenz Interacts with Hormones Involved in Appetite and Satiety, Affecting Body Weight in Mice.","authors":"Rojas-Osornio, Sandra Angélica; Manuel-Apolinar, Leticia; Crespo-Ramírez, Minerva; Paredes-Cervantes, Vladimir; Mata-Marín, Antonio; Molina-López, José; Pérez de la Mora, Miguel; Borroto-Escuela, Dasiel; Martínez-Lara, Ricardo; Tesoro-Cruz, Emiliano","year":2026,"journal":"International journal of molecular sciences, 27(2)","doi":"10.3390/ijms27020735","pmid":"41596392","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"After 36 days of efavirenz (10 mg/kg oral) in CD1 mice:\n\n- **Appetite signaling increased**: Serum ghrelin rose, and hypothalamic expression of GHS-R1a (ghrelin receptor) and NPYR1 (neuropeptide Y receptor 1) were upregulated.\n- **Eating behavior changed**: Food intake increased and sucrose preference was elevated, consistent with enhanced reward-driven eating.\n- **Paradoxical weight loss**: Despite eating more, mice in the efavirenz group lost weight.\n- **Metabolic disruption**: Triglycerides and cholesterol increased.\n- **Leptin findings**: Serum leptin, soluble leptin receptor (sOB-R), and free leptin index showed that the increased hunger was not caused by reduced satiety signaling — rather, hunger was independently stimulated through the ghrelin/NPY axis.","whyItMatters":"Over 39 million people worldwide live with HIV, and most take antiretroviral drugs long-term. Metabolic side effects — including obesity, dyslipidemia, and insulin resistance — are major quality-of-life concerns. Understanding exactly how these drugs alter peptide hormone signaling in the brain's appetite centers could lead to targeted interventions (such as ghrelin antagonists or NPY modulators) to manage these side effects.","specificNumbers":"","methodology":"CD1 mice received efavirenz (10 mg/kg) or distilled water (control) orally for 36 days. Measurements included body weight and food intake throughout treatment, metabolic panels (glucose, triglycerides, cholesterol), serum peptide hormones (leptin, sOB-R, ghrelin), hypothalamic receptor expression (GHS-R1a, NPYR1, leptin) via immunohistochemistry or similar techniques, and a sucrose preference test.","limitations":"The study was conducted in mice, and efavirenz metabolism may differ from humans. Only male mice were studied. The paradoxical weight loss despite increased intake wasn't mechanistically explained — energy expenditure was not directly measured. The 36-day treatment period may not capture long-term metabolic adaptations. The dose used (10 mg/kg) may not directly translate to human therapeutic doses."},{"rthcId":"RPEP-16008","title":"Analysis of Antimicrobial Peptide Expression Under Acute and Chronic Alcohol Exposure: A Cross-Sectional Study and a Systematic Review of the Literature.","authors":"Rojas-Pirela, Maura; Herrera-Flores, Cristian; Costa-Alba, Pilar; Salete-Granado, Daniel; Aguilar, María-Lourdes; Puertas-Miranda, David; Cicuéndez, Beatriz; Pérez-Nieto, María-Ángeles; Pérez-Albornoz, Candy; Folgueira, Cintia; Mora, Alfonso; Sabio, Guadalupe; Marcos, Miguel","year":2026,"journal":"International journal of molecular sciences, 27(4)","doi":"10.3390/ijms27042026","pmid":"41752164","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16009","title":"Biophysical approaches to antimicrobial peptide-membrane characterization.","authors":"Roldán, A; Fernández-García, P; Lladó, V; Torres, M; Escribá, P V; Salvador-Castell, M","year":2026,"journal":"Biochimica et biophysica acta. Biomembranes, 1868(2), 184499","doi":"10.1016/j.bbamem.2026.184499","pmid":"41539421","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review establishes that AMPs exploit a fundamental difference between bacterial and human cells: bacterial membranes carry a negative charge, while eukaryotic (human) membranes are largely neutral. The positively charged, amphipathic structure of AMPs drives their selective binding to bacteria.\n\nMultiple biophysical techniques can measure distinct aspects of this interaction. Differential scanning calorimetry reveals how peptides alter membrane stability and phase behavior. X-ray diffraction shows structural changes in lipid packing. NMR provides atomic-level detail of peptide orientation within membranes. Fluorescence spectroscopy can track pore formation, permeability changes, and binding affinities in real time. Together, these methods allow researchers to rationally design new AMPs with improved selectivity and potency.","whyItMatters":"With antibiotic resistance becoming a global health crisis, antimicrobial peptides represent one of the most promising alternatives. But designing effective AMPs requires understanding exactly how they interact with membranes at the molecular level. This review serves as a practical roadmap for researchers developing the next generation of peptide-based antibiotics, helping them choose the right tools to characterize their candidates.","specificNumbers":"","methodology":"This is a review article that synthesizes published research on biophysical characterization methods for antimicrobial peptides. It covers studies using model lipid membranes (artificial membranes that mimic bacterial or human cell surfaces) and evaluates the strengths of different analytical techniques for measuring peptide-membrane interactions.","limitations":"As a review article, this paper synthesizes existing research rather than presenting new experimental data. Model lipid membranes, while useful, are simplified versions of real biological membranes and may not fully capture the complexity of in vivo peptide-membrane interactions. The review focuses on biophysical characterization and does not address clinical translation challenges such as stability, toxicity, or delivery."},{"rthcId":"RPEP-16010","title":"Effectiveness and safety of anti-CGRP monoclonal antibodies in hemiplegic migraine: an individual patient quantitative analysis.","authors":"Romozzi, Marina; Palermo, Matteo; Danno, Daisuke; Katsuki, Masahito; Tosto, Federico; Signorelli, Francesco; Vollono, Catello; Matsumori, Yasuhiko; Calabresi, Paolo; Ornello, Raffaele; Iannone, Luigi Francesco","year":2026,"journal":"The journal of headache and pain, 27(1)","doi":"10.1186/s10194-026-02283-5","pmid":"41618146","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In a pooled analysis of 13 hemiplegic migraine patients treated with anti-CGRP monoclonal antibodies, median monthly aura days dropped from 3 to 0.6 (p=0.018) and MIDAS disability scores fell from 88 to 28 (p=0.018) at three months.\n\nMonthly headache days decreased numerically from 18 to 9, though this did not reach statistical significance (p=0.077). Notably, 83% of patients achieved greater than 50% reduction in both headache days and aura frequency, and 75% saw more than 50% improvement in disability scores. No adverse events were reported across the entire cohort.","whyItMatters":"Hemiplegic migraine patients are systematically excluded from randomized controlled trials, leaving clinicians with almost no evidence-based treatment options. This analysis provides the first pooled evidence that anti-CGRP antibodies — already proven effective for other migraine types — may also work for this rare and highly disabling condition, potentially opening a new treatment avenue for an underserved patient population.","specificNumbers":"","methodology":"The researchers conducted a systematic review following PRISMA guidelines, searching PubMed, Scopus, and Web of Science for any studies reporting hemiplegic migraine patients treated with anti-CGRP antibodies. They extracted individual patient data from the six qualifying studies (four case series and two case reports) and performed pooled analyses comparing outcomes at baseline versus three months of treatment.","limitations":"The analysis included only 13 patients from six small studies (case series and case reports), with no randomized controlled data. The overall evidence certainty was rated very low by GRADE assessment. Without a control group, it's impossible to separate treatment effects from natural disease fluctuation or placebo response. The three-month follow-up is also relatively short for evaluating long-term effectiveness and safety."},{"rthcId":"RPEP-16011","title":"From antibiotic to peptide siderophore conjugates as modular strategies against multidrug-resistant bacteria.","authors":"Roque-Borda, Cesar Augusto; Zhang, Qi; de la Torre, Beatriz G; Albericio, Fernando; Perdigão, João; Pavan, Fernando Rogério","year":2026,"journal":"Clinical microbiology reviews, e0017425","doi":"10.1128/cmr.00174-25","pmid":"41778900","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16012","title":"Synergistic combinations of antimicrobial peptides and conventional antibiotics: A strategy to delay resistance emergence in World Health Organization priority bacteria.","authors":"Roque-Borda, Cesar Augusto; Zhang, Qi; Nguyen, Thi Phuong Truc; Nguyen, Thi Thu Hoai; Medhi, Himadri; Rodrigues, Heitor Leocádio de Souza; Canales Carnero, Christian S; Sutherland, Darcy; Helmy, Naiera M; Araveti, Prasanna Babu; de la Torre, Beatriz G; Albericio, Fernando; Pavan, Fernando Rogério","year":2026,"journal":"Pharmacological reviews, 78(1), 100104","doi":"10.1016/j.pharmr.2025.100104","pmid":"41389440","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16013","title":"Glycemic Impact of Non-Nutritive Sweeteners in Health and Type 2 Diabetes.","authors":"Rose, Braden D; Kreuch, Denise; Wu, Tongzhi; Horowitz, Michael; Rayner, Christopher K; Page, Amanda J; Miller, Caroline L; Young, Richard L","year":2026,"journal":"Nutrition reviews","doi":"10.1093/nutrit/nuaf313","pmid":"41706019","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16014","title":"The effects of a 12-week lifestyle intervention on incretin response during an oral glucose tolerance test in Latino youth with obesity and impaired glucose tolerance.","authors":"Rosenberg, Jared; Williams, Allison; Gano, Anny; Deak, Molly M; Shaibi, Gabriel Q; Kim, Joon Young","year":2026,"journal":"Journal of diabetes and its complications, 40(1), 109228","doi":"10.1016/j.jdiacomp.2025.109228","pmid":"41289824","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16015","title":"Efficacy and safety of once-daily oral orforglipron compared with oral semaglutide in adults with type 2 diabetes (ACHIEVE-3): a multinational, multicentre, non-inferiority, open-label, randomised, phase 3 trial.","authors":"Rosenstock, Julio; Yabe, Daisuke; Cox, David; Li, Jianghao; Denning, Max; Wu, Wen-Shuo; Liu, Rong; Zhao, Youna","year":2026,"journal":"Lancet (London, England)","doi":"10.1016/S0140-6736(26)00202-3","pmid":"41765029","tags":["orforglipron","semaglutide","GLP-1-agonists","type-2-diabetes"],"studyType":"rct","evidenceStrength":"high","keyFinding":"In a 52-week phase 3 trial of 1,698 adults with type 2 diabetes, oral orforglipron was not only non-inferior but statistically superior to oral semaglutide at lowering blood sugar. Orforglipron 36 mg reduced HbA1c by 1.91% from baseline vs. 1.47% for semaglutide 14 mg (treatment difference -0.44%, p<0.0001). Even the lower 12 mg orforglipron dose beat the higher semaglutide 14 mg dose (-0.24% difference, p=0.005).\n\nHowever, orforglipron came with trade-offs: higher rates of gastrointestinal side effects (58-59% vs. 37-45%), more treatment discontinuations due to adverse events (9-10% vs. 4-5%), and a greater increase in pulse rate (3.7-4.7 bpm vs. 1.0-1.5 bpm).","whyItMatters":"Orforglipron is the first non-peptide oral GLP-1 receptor agonist — meaning it's a small molecule, not a peptide, and doesn't need the special absorption-enhancing formulation that oral semaglutide requires. Patients can take it without food or water restrictions. This head-to-head victory over oral semaglutide on blood sugar control positions orforglipron as a potentially transformative option, though the higher side effect burden will be a key factor in clinical adoption.","specificNumbers":"n=1,698 · 52 weeks · HbA1c reduction: orforglipron 36mg -1.91% vs semaglutide 14mg -1.47% · Treatment difference -0.44% (p<0.0001) · GI events: 58-59% orforglipron vs 37-45% semaglutide · Discontinuation: 9-10% vs 4-5% · Pulse increase: 3.7-4.7 bpm vs 1.0-1.5 bpm","methodology":"52-week, randomized, open-label, active-controlled phase 3 trial across 131 centers in Argentina, China, Japan, Mexico, and the USA. 1,698 adults with T2D on metformin (≥1500 mg/day), HbA1c 7.0-10.5%, BMI ≥25 were randomized 1:1:1:1 to orforglipron 12 mg, orforglipron 36 mg, semaglutide 7 mg, or semaglutide 14 mg. Primary endpoint was non-inferiority of HbA1c change at week 52 with a 0.3% margin.","limitations":"Open-label design means participants and investigators knew which drug they were taking, which could introduce bias in reporting side effects. Funded by Eli Lilly (orforglipron's manufacturer). The study compared against currently available oral semaglutide doses — higher doses of oral semaglutide now in development were not included. Four deaths occurred across groups."},{"rthcId":"RPEP-16016","title":"The role of the incretin GIP in inflammation.","authors":"Rossi, Giada; Bucciarelli, Loredana; Cimino, Vincenzo; Fiorina, Paolo","year":2026,"journal":"Journal of endocrinological investigation, 49(2), 255-266","doi":"10.1007/s40618-025-02719-w","pmid":"41082103","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GIP's effects on inflammation are context-dependent and influenced by tissue-specific receptor expression and metabolic status. Experimental models show both pro-inflammatory and anti-inflammatory effects depending on the setting. GIP/GLP-1 dual agonists have demonstrated improved glycometabolic and inflammatory outcomes in clinical use, but the individual contributions of each pathway remain unclear.\n\nThe GIP receptor (GIPR) is expressed on immune cells and tissues beyond the pancreas, providing a biological basis for immunomodulatory effects. The review highlights GIPR as a promising but understudied target in the emerging field of immunometabolism.","whyItMatters":"Chronic low-grade inflammation is now recognized as a key driver of type 2 diabetes, obesity, cardiovascular disease, and metabolic syndrome. As millions of patients take tirzepatide and newer dual/triple agonists, understanding GIP's specific contribution to anti-inflammatory effects is essential for optimizing these drugs, identifying which patients benefit most, and developing next-generation therapies that target inflammation more precisely.","specificNumbers":"","methodology":"Comprehensive narrative review of the scientific literature from GIP's discovery to present, examining preclinical and clinical evidence linking GIP to inflammatory processes. Pharmacological approaches targeting the GIP receptor — including GIP-based multi-target (dual and triple agonist) therapies — are discussed in relation to inflammatory outcomes.","limitations":"Clinical data on GIP's anti-inflammatory effects are still limited. Most evidence comes from preclinical models, which may not translate directly to humans. The context-dependent nature of GIP's effects (sometimes pro-inflammatory, sometimes anti-inflammatory) makes it difficult to predict clinical outcomes. The review acknowledges that disentangling GIP from GLP-1 contributions in dual agonist therapies remains an unsolved challenge."},{"rthcId":"RPEP-16017","title":"Smart zwitterionic biodegradable hydrogel for sustained peptide delivery: Application to the neurotherapeutic peptide NX210c.","authors":"Rosson, Elise; Thomas, Eloise; Sidi-Boumedine, Jacqueline; Kryza, David; Couderc, Marie; Brichart, Thomas; Geloen, Alain; Montembault, Alexandra; David, Laurent; Lux, François; Godfrin, Yann; Tillement, Olivier","year":2026,"journal":"Biomaterials advances, 178, 214437","doi":"10.1016/j.bioadv.2025.214437","pmid":"40763683","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The chitosan-DOTAGA hydrogel formed in situ under physiological conditions via electrostatic and hydrogen bonding interactions, requiring no solvents. Pharmacokinetic comparison in rodents showed dramatic differences:\n- IV injection: peptide cleared within 1 hour\n- Free subcutaneous NX210c: eliminated within approximately 3 hours\n- Hydrogel delivery: peptide levels sustained for 10-15 days with area under the curve (AUC) dozens of times higher than IV\n\nIn vivo studies confirmed subcutaneous injectability, gelation ability, biocompatibility, and complete biodegradation within a few weeks.","whyItMatters":"Many therapeutic peptides fail clinically not because they don't work, but because they're cleared from the body too quickly. This hydrogel technology addresses one of the biggest barriers in peptide therapeutics — short half-life — converting a treatment requiring continuous hospital-based IV infusion into a simple subcutaneous injection lasting weeks. If applicable to other peptides, this platform could make many promising peptide drugs clinically viable.","specificNumbers":"","methodology":"Researchers developed chitosan-based hydrogels functionalized with the DOTAGA macrocyclic ligand. Hydrogel candidates were screened in vitro for injectability, gelation properties, peptide loading capacity, and release kinetics. In vivo validation was performed in rodents, assessing subcutaneous injectability, gel formation, biocompatibility, and biodegradation. Pharmacokinetic studies compared NX210c blood levels after IV injection, free subcutaneous injection, and hydrogel-mediated subcutaneous delivery.","limitations":"Therapeutic efficacy of NX210c delivered via the hydrogel was not assessed — only pharmacokinetics were evaluated. The biodistribution and brain penetration of sustained-release NX210c were not reported. Long-term safety of repeated hydrogel injections was not studied. The DOTAGA functionalization adds regulatory complexity. Scale-up from laboratory to clinical manufacturing was not addressed. Only rodent models were used."},{"rthcId":"RPEP-16018","title":"The role of therapeutic cancer vaccines in the modern immunotherapy era: State of the art with recent progress and future challenges.","authors":"Rota, Michele; Torresan, Irene; Palmerio, Silvia; Tasselli, Ester; Rossi, Alice; Zivi, Andrea; Zacchi, Francesca","year":2026,"journal":"Critical reviews in oncology/hematology, 217, 105068","doi":"10.1016/j.critrevonc.2025.105068","pmid":"41349781","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16019","title":"Current and Future Pharmacological Interventions for Acquired Hypothalamic Obesity.","authors":"Roth, Christian L; Doelman-Oldenburger, Nathalie J; van Santen, Hanneke M","year":2026,"journal":"Drugs","doi":"10.1007/s40265-025-02280-z","pmid":"41678022","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16020","title":"A comparison of the effect of SMA derivatives on the structural topology and dynamics of two bacteriophage peptides.","authors":"Rotich, Nancy C; Okorafor, Evelyn A; Sahu, Indra D; Shah, Muhammad Zeeshan; Konkolewicz, Dominik; Lorigan, Gary A","year":2026,"journal":"Chemistry and physics of lipids, 274, 105562","doi":"10.1016/j.chemphyslip.2025.105562","pmid":"41344551","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16021","title":"Effect of bempedoic acid on incretin axis and systemic and liver inflammation: a pilot, monocentric study.","authors":"Rovera, Chiara; Del Zoppo, Alice; Petralli, Giovanni; Moriconi, Diego; Rossi, Chiara; Distaso, Mariarosaria; Brunetto, Maurizia Rossana; Ferrannini, Ele; Raggi, Francesco; Solini, Anna","year":2026,"journal":"Nutrition, metabolism, and cardiovascular diseases : NMCD, 36(2), 104373","doi":"10.1016/j.numecd.2025.104373","pmid":"41073213","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16022","title":"Optimization of patient and site engagement in the SYNCHRONIZE™ phase 3 clinical trial program for survodutide in obesity through clinical trial simulation.","authors":"Rubino, Domenica M; Mooney, Vicki; van de Walle, Viviënne; Baanstra, David; Daniëls, Wouter; Recaldin, Christopher; Nadglowski, Joe","year":2026,"journal":"Contemporary clinical trials communications, 49, 101611","doi":"10.1016/j.conctc.2026.101611","pmid":"41704810","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16023","title":"CGRP and Migraine: Real-World Insights and Future Therapeutic Directions.","authors":"Russo, Andrew F; Kaiser, Eric A","year":2026,"journal":"Annual review of medicine, 77(1), 415-432","doi":"10.1146/annurev-med-050224-111631","pmid":"41296986","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16024","title":"Glucagon-like peptide-1 receptor signaling deficiency exacerbates hematopoietic stem cell graft rejection in mice.","authors":"Rusznak, Mark; Sierra-Hernandez, Daniela; Dupuy, Catherine; Toki, Shinji; Wu, Ashley Y; Rao, Uttam; Abney, Masako; Zhang, Jian; Hu, Qianni; Warren, Christian M; Drucker, Daniel J; Niswender, Kevin D; Engelhardt, Brian; Kim, Tae Kon; Gibson-Corley, Katherine N; Cahill, Katherine N; Cooke, Kenneth R; Peebles, R Stokes","year":2026,"journal":"Journal of immunology (Baltimore, Md. : 1950), 215(1)","doi":"10.1093/jimmun/vkaf251","pmid":"40990163","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16025","title":"Hidden Targets in Cancer Immunotherapy: The Potential of \"Dark Matter\" Neoantigens.","authors":"Rwandamuriye, Francois Xavier; Redwood, Alec J; Creaney, Jenette; Robinson, Bruce W S","year":2026,"journal":"Vaccines, 14(1)","doi":"10.3390/vaccines14010104","pmid":"41601019","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16026","title":"Ethical considerations for semaglutide use in children.","authors":"Ryan, Nanette; Wilkinson, Dominic; Savulescu, Julian","year":2026,"journal":"Archives of disease in childhood","doi":"10.1136/archdischild-2025-329747","pmid":"41494820","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16027","title":"The Ethics of Ozempic and Wegovy.","authors":"Ryan, Nanette; Savulescu, Julian","year":2026,"journal":"Journal of medical ethics, 52(3), 185-193","doi":"10.1136/jme-2024-110374","pmid":"39848681","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16028","title":"The Ethics of Wegovy in Pediatric Mental Health.","authors":"Ryan, Nanette; Savulescu, Julian","year":2026,"journal":"Bioethics","doi":"10.1111/bioe.70087","pmid":"41614219","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16029","title":"The ethics of Wegovy: promoting autonomy in pediatric care.","authors":"Ryan, Nanette; Savulescu, Julian","year":2026,"journal":"Medicine, health care, and philosophy, 29(1), 243-255","doi":"10.1007/s11019-025-10300-8","pmid":"41065944","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16030","title":"Psychiatric effects of GLP-1 receptor agonists: A systematic review of emerging evidence.","authors":"Sa, Brianna; Maristany, Anthony; Subramaniam, Ashwin; Guillen, Ryan; Buonocore, Brooke; Smith, Audrey; Oldak, Sean E; Padilla, Vanessa","year":2026,"journal":"Diabetes, obesity & metabolism, 28(1), 50-59","doi":"10.1111/dom.70198","pmid":"41126551","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"This systematic review of GLP-1 receptor agonist psychiatric effects found a mixed but intriguing picture: modest antidepressant effects were observed across studies, and there were signs of potential benefit for eating disorders and substance use disorders — conditions driven by reward system dysregulation. However, the link between GLP-1 drugs and suicidal thoughts remained inconclusive, with studies showing inconsistent results. In people with schizophrenia, GLP-1 drugs improved metabolic health but did not consistently affect psychiatric symptoms.","whyItMatters":"With tens of millions of people now taking GLP-1 drugs like semaglutide and tirzepatide, understanding their effects on mental health is critical. Reports of reduced alcohol cravings, changed relationships with food, and concerns about suicidal ideation have made headlines. This review is the first systematic attempt to sort signal from noise across the full spectrum of psychiatric effects — and the answer is that some effects look real (antidepressant, anti-craving) while others (suicidality) remain unresolved.","specificNumbers":"","methodology":"The researchers systematically searched PubMed/MEDLINE, Cochrane Central Register, Embase, and Web of Science for all studies examining associations between GLP-1 receptor agonists and psychiatric outcomes including depression, suicidality, eating disorders, substance use disorders, and schizophrenia. Studies were evaluated for quality and findings were synthesized narratively across each psychiatric domain.","limitations":"The included studies varied widely in dosing, clinical indication (diabetes vs. obesity), and whether patients had pre-existing psychiatric conditions. People with psychiatric comorbidities were consistently underrepresented in the original trials. Sample diversity was limited across studies. The heterogeneity made it difficult to draw firm conclusions, particularly about suicidality risk."},{"rthcId":"RPEP-16031","title":"Retrospective chart review on psychiatric manifestations of GLP-1 agonist usage.","authors":"Sa, Brianna; Maristany, Anthony; Subramaniam, Ashwin; Kumbkarni, Nayha; Lange, Rachel; Oldak, Sean; Buciuc, Adela-Georgiana; Padilla, Vanessa","year":2026,"journal":"Journal of psychiatric research, 195, 92-96","doi":"10.1016/j.jpsychires.2026.01.042","pmid":"41616750","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16032","title":"Synergistic Effect of Phenylalanine Residues Governs the Mechanism of Membrane Disrupting Action of Aurein 1.2.","authors":"Saadatmand, Zahra Nadia; Zhu, Shiwen; Mechler, Adam; Wohland, Thorsten","year":2026,"journal":"Journal of medicinal chemistry, 69(3), 2712-2724","doi":"10.1021/acs.jmedchem.5c02612","pmid":"41556696","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16033","title":"Repurposing glucagon-like peptide-1 receptor agonists for the treatment of neurodegenerative disorders.","authors":"Sabbagh, Marwan N; Cummings, Jeffrey L; Ballard, Clive; van der Flier, Wiesje M; Heneka, Michael T; Holst, Jens Juul; Knudsen, Lotte Bjerre; Salloway, Stephen; Tansey, Malú Gámez; Drucker, Daniel J","year":2026,"journal":"Nature aging, 6(1), 56-67","doi":"10.1038/s43587-025-01029-3","pmid":"41419667","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16034","title":"Genome and transcriptome mining of the corazonin (Crz)-like peptide and gonadotropin-releasing hormone (GnRH)-like peptides in the spotted Babylon, Babylonia areolata.","authors":"Saetan, Uraipan; Kornthong, Napamanee; Duangprom, Supawadee; Tanasawet, Supita; Sukketsiri, Wanida; Tamtin, Montakan; Phanthong, Phetcharat; Sanprick, Amornrat; Chinfak, Narainrit; Saetan, Jirawat","year":2026,"journal":"Comparative biochemistry and physiology. Part D, Genomics & proteomics, 58, 101738","doi":"10.1016/j.cbd.2025.101738","pmid":"41529500","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16035","title":"Protecting the endocrine axis in immuno-oncology: GLP-1 receptor agonists as host-directed modulators in colorectal cancer.","authors":"Saghafi, Samira; Yaghoubi, Mohammad Ali; Safarpour, Hossein; Raeisi, Hamideh; Mousavi, Zohreh","year":2026,"journal":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 194, 118948","doi":"10.1016/j.biopha.2025.118948","pmid":"41496347","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16036","title":"A Systematic Review and Meta-Analysis of Semaglutide Effects on Adipose Tissue and Emerging Effects on Brain and Cognition.","authors":"Saghazadeh, Amene; Dolatshahi, Mahsa; Mohammadi, Soheil; Kassani, Sara Hosseinzadeh; Naghashzadeh, Mahshid; Ippolito, Joseph E; Sirlin, Claude B; Mittendorfer, Bettina; Brier, Matthew R; Schindler, Suzanne E; Morris, John C; Mou, Danny; Soudah, Hani Charles; Benzinger, Tammie L S; Raji, Cyrus A","year":2026,"journal":"Obesity reviews : an official journal of the International Association for the Study of Obesity, e70108","doi":"10.1111/obr.70108","pmid":"41766347","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16037","title":"Nanobody-Based Bioconjugates as Potent and Broadly Active Inhibitors of HIV Entry.","authors":"Saha, Shubhra Jyoti; Kumariya, Rashmi; Davis, Phoenix A; Tourtellott, Emily; Doria-Rose, Nicole; Bewley, Carole A; Cheloha, Ross W","year":2026,"journal":"Journal of the American Chemical Society, 148(5), 5793-5806","doi":"10.1021/jacs.5c22670","pmid":"41592176","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16038","title":"Changes in fibroblast growth factor 21 levels associated with alcohol consumption and smoking cessation.","authors":"Sailer, Clara O; Vogel, Cyril F; Monnerat, Sophie; Probst, Leila; Christ-Crain, Mirjam; Winzeler, Bettina; Refardt, Julie","year":2026,"journal":"Endocrine connections, 15(1)","doi":"10.1530/EC-25-0713","pmid":"41384608","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16039","title":"Research note: Antimicrobial properties of commercial black soldier fly (Hermetia illucens) meal against gram-positive and gram-negative bacteria.","authors":"Saini, Gauri S; Jiao, Zijin; Low, Li Yi; Sur, Somok; Zorrilla, Martin J; Chen, Wenqian","year":2026,"journal":"Poultry science, 105(4), 106424","doi":"10.1016/j.psj.2026.106424","pmid":"41610614","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16040","title":"Effect of Fluid Restriction in Heart Failure: A Meta-Analysis of Randomized Controlled Trials.","authors":"Sajid, Maryam; Ahmed, Shahzaib; Khan, Taimor Mohammed; Salim, Hussain; Husseiny, Yousef M; Qureshi, Shaheer; Sajjad, Asim; Bilal, Abdur Rafay; Waqas, Saad Ahmed","year":2026,"journal":"Cardiology in review","doi":"10.1097/CRD.0000000000001244","pmid":"41860314","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16041","title":"Effects of Semaglutide on BMI and Cardiometabolic Profile in Adolescents With Variants in Monogenic Obesity-Related Genes.","authors":"Salama, Mostafa; Hassan, Doha; Vairo, Filippo Pinto E; Lteif, Aida; Hentz, Roland; Olson, Ole; Pittock, Siobhan; Al Nofal, Alaa; Creo, Ana; Kumar, Seema","year":2026,"journal":"Pediatric obesity, 21(2), e70091","doi":"10.1111/ijpo.70091","pmid":"41667135","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16042","title":"Treatment Approaches for Obesity in Children With Heterozygous MC4R Variants.","authors":"Salama, Mostafa; Saba, Leslie; Valdez, Lourdes; Lteif, Aida; Kumar, Seema","year":2026,"journal":"Clinical obesity, 16(1), e70069","doi":"10.1111/cob.70069","pmid":"41489233","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16043","title":"Regorafenib modulates glucose metabolism, insulin/GLP-1 signaling, and tau pathology in an STZ-induced model of Alzheimer's disease.","authors":"Salarinasab, Sadegh; Asgari Taei, Afsaneh; Kaveh, Neda; Karima, Saeed; Nikzamir, Abdolrahim; Dargahi, Leila","year":2026,"journal":"Naunyn-Schmiedeberg's archives of pharmacology, 399(2), 2989-3000","doi":"10.1007/s00210-025-04545-6","pmid":"41003702","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16044","title":"Additive Effects of Dorzagliatin and Glucagon-Like Peptide 1 Receptor Agonism in a Novel Mouse Model of GCK-MODY and in Obese db/db Mice.","authors":"Salazar, Shadai; Delgadillo-Silva, Luis Fernando; Carapeto, Priscila; Kenfaoui, Mohamed Mourad; Dakessian, Karen; Melhem, Rana; Provencher-Girard, Audrey; Ostinelli, Giada; Turgeon, Julie; Kaci, Imane; Migneault, Francis; Huising, Mark O; Hébert, Marie-Josée; Chaker-Margot, Malik; Rutter, Guy A","year":2026,"journal":"Diabetes, 75(1), 99-114","doi":"10.2337/db25-0520","pmid":"41196662","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16045","title":"Nano-antimicrobial peptides (Nano-AMPs) to combat resistant gram-negative bacteria.","authors":"Saleem, Naveed; Kumar, Naresh; El-Omar, Emad; Willcox, Mark; Jiang, Xiao-Tao","year":2026,"journal":"Drug delivery and translational research","doi":"10.1007/s13346-026-02085-x","pmid":"41772350","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16046","title":"GLP1-RAs: long-term use versus discontinuation events of an emerging therapy for obesity and cardiovascular diseases.","authors":"Salerno, Elia Nunzio Maria; Fumarulo, Isabella; Garramone, Barbara; Vaccarella, Marcello; Ierardi, Carolina; Burzotta, Francesco; Aspromonte, Nadia","year":2026,"journal":"Current problems in cardiology, 51(2), 103213","doi":"10.1016/j.cpcardiol.2025.103213","pmid":"41297647","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 receptor agonists have become first-line therapy for multiple clinical settings based on strong scientific evidence for obesity, type 2 diabetes, hypertension, heart failure, and cardiovascular disease. However, concerns about long-term adverse effects lead clinicians to prescribe them for limited periods, often discontinuing once weight reduction is achieved. The review examines evidence comparing the risks of long-term GLP-1RA use (potential adverse effects) against the risks of discontinuation (weight regain, loss of cardiovascular and metabolic benefits).","whyItMatters":"This is one of the most important unanswered questions in obesity medicine today. Tens of millions of people are now on GLP-1 receptor agonists, and many face the decision of whether to continue indefinitely or stop after achieving weight loss. The evidence suggests that discontinuation reverses many benefits, but concerns about unknown long-term effects create clinical uncertainty. This review helps frame the risk-benefit calculation.","specificNumbers":"","methodology":"Narrative literature review examining clinical effects and indications of GLP-1 receptor agonists, with a focus on comparing long-term safety data against the consequences of treatment discontinuation. Published in a cardiology journal, reflecting the cardiovascular perspective on this question.","limitations":"This is a narrative review, not a systematic review or meta-analysis. Long-term safety data for GLP-1RAs beyond 2-5 years is limited, making definitive conclusions about very long-term risks difficult. The review focuses on the risk comparison framework but may not cover all emerging safety signals. Individual patient factors affecting the risk-benefit balance are not addressed in detail."},{"rthcId":"RPEP-16047","title":"GLP-1 Receptor Agonist Exenatide Protects Against Doxorubicin-Induced Cardiotoxicity Through the SIRT1 Pathway: An Electrocardiographic, 99mTc-PYP Scintigraphic, and Biochemical Study.","authors":"Salmanoglu, Musa; Ercan, Gulcin; Genç, Hanife Seyda; Gül, Serdar Savaş; Aygün, Hatice","year":2026,"journal":"Medicina (Kaunas, Lithuania), 62(1)","doi":"10.3390/medicina62010143","pmid":"41597428","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16048","title":"GLP-1 agonist, semaglutide use in acute pulmonary embolism recovery: a four-week proof-of-concept study including proteomic profiling.","authors":"Samaranayake, Chinthaka B; Chen, Yen-Cheng; Fang, Min; Rhodes, Christopher J; Song, Shanshan; Sabrin, Farah; Ashek, Ali; Bonnici, Kathleen; Mukherjee, Bhashkar; Howard, Luke S; Pinguel, Joy; Rawal, Bhavin; Semple, Tom; Price, Laura C; Wort, S John; Rudd, Timothy; Zhao, Lan; McCabe, Colm","year":2026,"journal":"European heart journal open, 6(1), oeaf170","doi":"10.1093/ehjopen/oeaf170","pmid":"41536961","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16049","title":"The essential role of the physiotherapy profession in incretin-based weight loss.","authors":"Sampford, Jade; Myers-Ingram, Richard; Jones, Gareth D; Cork, Simon","year":2026,"journal":"Physiotherapy, 130, 101840","doi":"10.1016/j.physio.2025.101840","pmid":"41273939","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16050","title":"GLP-1 RAs vs. SGLT2is: Divergent Pathways of Cardiovascular Inflammation Control in Obesity-Associated Diabetes.","authors":"Samuel, Ailish Hephzibah; Kshatri, Abhishek Hanumanpratap Singh; Babu, Rithwik Nanda; Patel, Harsh Shirishkumar; Viswanathan, Smera Hari; Challa, Mani Shankar Reddy; Swathi, N L","year":2026,"journal":"Annales d'endocrinologie, 102494","doi":"10.1016/j.ando.2026.102494","pmid":"41713726","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16051","title":"Liraglutide Ameliorates Gamma Radiation-Induced Hepatic Damage in Rats: The Role of an Autophagy Flux Activation via LKB1/AMPK/mTOR Axis.","authors":"Samy, Esraa M; Shaaban, Esmat A","year":2026,"journal":"Archives of medical research, 57(2), 103296","doi":"10.1016/j.arcmed.2025.103296","pmid":"40913889","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16052","title":"Epitalon increases telomere length in human cell lines through telomerase upregulation or ALT activity.","authors":"Sanchez-Martin, Veronica; Lopez-Fernandez, Laura; Celdrán, Andrea; Aranda, María Cruz; Martin, Francisca; Cabello-Lobato, María José; Aguilera, Andrés; Jaeger, Sven","year":2026,"journal":"Biochemical and biophysical research communications, 758, 151805","doi":"10.1016/j.bbrc.2025.151805","pmid":"40908429","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16053","title":"Wall Teichoic Acids Are Direct Molecular Targets of Antimicrobial Peptides in Gram-Positive Bacteria.","authors":"Sandeep, Arunima; Zaatouf, Laila; Arnold, Alexandre A; Warschawski, Dror E; Marcotte, Isabelle","year":2026,"journal":"Journal of the American Chemical Society, 148(7), 7240-7250","doi":"10.1021/jacs.5c18971","pmid":"41667126","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16054","title":"Proteomic signatures of carotid plaque vulnerability: Proteolysis, inflammation, metabolic reprogramming, and lipid dysregulation.","authors":"Sandoval, Camilo Polania; Meschia, James F; Prudencio, Mercedes; Gendron, Tania; Jacobs, Christopher; Beegle, Richard D; Sandhu, Sukhwinder J S; Mangalaparthi, Kiran K; Sung, Jaeyun; Zhao, Xiaowei; Nassar, Aziza; Farres, Houssam; Petrucelli, Leonard; Pandey, Akhilesh; Erben, Young","year":2026,"journal":"JVS-vascular science, 7, 100404","doi":"10.1016/j.jvssci.2025.100404","pmid":"41640976","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Out of 3,267 proteins identified in carotid plaque tissue, 15 reached high-confidence significance (q ≤ 0.25) and were all upregulated in vulnerable plaques. These included matrix metalloproteinases (MMP7, MMP9, MMP1), neutrophil-derived proteins (cathelicidin antimicrobial peptide, azurocidin, lactotransferrin, myeloperoxidase), inflammatory regulators (interleukin-1 receptor antagonist, interleukin-4-induced protein), glycolytic enzymes (hexokinase-2 and hexokinase-3), and lipid-handling proteins (lipoprotein-associated phospholipase A2, apolipoprotein B, paraoxonase-1).\n\nAn additional 17 exploratory proteins showed nominal significance with at least a 2-fold change, and 366 more proteins reached nominal significance with smaller fold changes.","whyItMatters":"Stroke remains a leading cause of death and disability, and carotid plaque rupture is a major trigger. Currently, decisions about surgical intervention rely heavily on imaging, which doesn't always capture the molecular instability within a plaque. Identifying protein biomarkers — especially peptides and enzymes actively involved in plaque breakdown — could lead to blood tests or imaging markers that flag high-risk patients before a stroke occurs, enabling earlier and more targeted prevention.","specificNumbers":"","methodology":"The researchers collected 28 carotid plaque specimens from 27 patients undergoing endarterectomy (surgical plaque removal). Plaques were classified as vulnerable or nonvulnerable (14 each) based on preoperative MRI with vessel wall imaging. Protein profiling was performed using a tandem mass tag-based multiplexing strategy followed by mass spectrometry. Protein levels were normalized, log2-transformed, and compared using two-sample t-tests with correction for multiple testing using the Benjamini-Hochberg method.","limitations":"The sample size was relatively small at 28 plaques from 27 patients, which limits statistical power and generalizability. The study was cross-sectional, meaning it cannot establish whether the identified proteins cause plaque instability or are simply associated with it. Vulnerability classification relied on imaging rather than histopathological confirmation. The findings have not yet been validated against actual stroke outcomes, which is acknowledged as the necessary next step."},{"rthcId":"RPEP-16055","title":"Antimicrobial Activity of Bioactive Peptides on Resistant Enterobacteriaceae and the Viability of Giardia duodenalis Cysts Isolated from Healthy Dogs.","authors":"Santaniello, Antonio; Roscetto, Emanuela; Galdiero, Umberto; Pepe, Paola; Bosco, Antonio; Boccino, Ida; Dipineto, Ludovico; Catania, Maria Rosaria; Grieco, Paolo","year":2026,"journal":"Veterinary sciences, 13(1)","doi":"10.3390/vetsci13010044","pmid":"41600700","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16056","title":"Enhancing the efficacy and selectivity of novel antimicrobial peptides against methicillin-resistant Staphylococcus aureus through computational and experimental approaches.","authors":"Santaweesuk, Parweenuch; Khumbungkha, Worada; Ngamsiri, Thararin; Pipattanaboon, Chonlatip; Phanthanawiboon, Supranee; Shoombuatong, Watshara; Kanthawong, Sakawrat","year":2026,"journal":"Biofouling, 42(1), 85-98","doi":"10.1080/08927014.2025.2604263","pmid":"41486693","tags":["antimicrobial-peptides","drug-resistant-bacteria"],"studyType":"in-vitro","evidenceStrength":"early-research","keyFinding":"Using AI-guided computational design combined with experimental validation, researchers created a modified antimicrobial peptide called TPF-M1 that effectively kills MRSA (methicillin-resistant Staphylococcus aureus). Starting from a natural peptide called Temporin-PF, they optimized it computationally to achieve an improved anti-MRSA score of 600.0.\n\nTPF-M1 showed enhanced killing activity against 10 different clinical MRSA isolates with good selectivity (meaning it targeted MRSA while showing low toxicity to human cells). At 20 μM, TPF-M1 also effectively reduced MRSA biofilm viability and disrupted biofilm structure — critical because biofilms are a major reason MRSA infections are so difficult to treat.","whyItMatters":"MRSA is one of the deadliest drug-resistant bacteria, classified by the WHO as a high-priority pathogen for new drug development. It kills tens of thousands of people annually in the US alone. Its ability to form biofilms makes it even harder to treat. This study demonstrates that AI-guided peptide design can rapidly optimize antimicrobial peptides to be more effective, more selective, and active against biofilms — accelerating a discovery process that was traditionally slow and labor-intensive.","specificNumbers":"Anti-MRSA score: 600.0 · Tested against 10 clinical MRSA isolates · Biofilm reduction at 20 μM · Low human cell toxicity · AI-guided optimization from Temporin-PF parent peptide","methodology":"Combined computational and experimental approach. Researchers used AI/computational tools to evaluate physicochemical properties and predict anti-MRSA activity of peptide variants. The lead peptide Temporin-PF was computationally modified to generate TPF-M1. Experimental validation included antimicrobial activity testing against 10 clinical MRSA isolates, bacterial selectivity assays, cytotoxicity testing against human cells, and antibiofilm assays using the transferable solid-phase pin lid method.","limitations":"This is an in vitro study — no animal or human testing has been performed. The 10 clinical isolates, while diverse, don't represent all MRSA strains globally. The anti-MRSA scoring system is specific to this study's computational framework. Long-term stability, pharmacokinetics, and in vivo efficacy remain unknown. Manufacturing scalability of the modified peptide is not addressed."},{"rthcId":"RPEP-16057","title":"Liraglutide and Exenatide in Alzheimer's Disease and Mild Cognitive Impairment: A Systematic Review and Meta-Analysis of Cognitive Outcomes.","authors":"Santos, Paula; Sá Filho, Alberto Souza; Aprigliano, Vicente; Duarte, Amanda G; Ribeiro, Natã Alegransi; Lombardo, Katia Marques; Fajemiroye, James Oluwagbamigbe; Buchholz, Artur Prediger; Vaz, Victor Renault; Chiappa, Gaspar R","year":2026,"journal":"Pharmaceutics, 18(1)","doi":"10.3390/pharmaceutics18010069","pmid":"41599176","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16058","title":"Identification and Characterization of Alamandine-(1-5), a New Component of the Renin-Angiotensin System.","authors":"Santos, Robson A S; Dias, Melissa Tainan Silva; Bessa, Amanda de Sá Martins; Barros, Carolina Fonseca; Itaborahy, Matheus F; da Silva, Filipe Alex; Gonçalves, Sthefanie Chaves de Almeida; Rodrigues-Ribeiro, Lucas; Ferraz, Kamylle Silva; Davel, Ana Paula; Nóbrega, Natália; Silva, Bruno Durante da; Scalzo, Sérgio; Soares, Pedro Alves; Dutra, João Batista Rodrigues; Lula, Ivana; Feng, Isadora Zhong Liang Ferreira; Vieira-Machado, Uri Flegler; de Godoy, Ana Caroline Ventris; Monteiro, Adelson Héric Alves; Eliezeck, Marcos; Sanches, Bruno; Monteiro, André; Magalhães, Gabriela; Soares, Nícia Pedreira; Pereira, Danilo Augusto Alves; Rezende Ribeiro, Júlia; Dias-Pinto, Maria Luiza; de Souza, Leandro Eziquiel; Silva, Amanda de A; Motta-Santos, Daisy; Bader, Michael; Alenina, Natália; Capettini, Luciano Dos Santos Aggum; Peliky Fontes, Marco Antônio; Haibara, Andrea Siqueira; Campos Vilella, Daniel; Verano-Braga, Thiago; Irigoyen, Maria Claudia; Marins, Fernanda Ribeiro; Castro, Carlos Henrique; Simões-E-Silva, Ana Cristina; Guatimosim, Silvia; Leite, M Fatima; Campagnole-Santos, Maria José","year":2026,"journal":"Circulation research, 138(1), e326174","doi":"10.1161/CIRCRESAHA.125.326174","pmid":"41221580","tags":[],"studyType":"basic-research","evidenceStrength":"moderate","keyFinding":"Researchers discovered a previously unknown peptide in the renin-angiotensin system called alamandine-(1-5), or Ala-(1-5). This five-amino-acid peptide is naturally present in the blood of both humans and rodents. It is formed from alamandine by ACE (angiotensin-converting enzyme) activity.\n\nAla-(1-5) produced a long-lasting blood pressure reduction (approximately 6 hours) in spontaneously hypertensive rats, associated with decreased cardiac output. It also increased baroreflex sensitivity, reduced heart contractility in isolated hearts and cardiomyocytes, and stimulated nitric oxide production through Mas, MrgD, and AT2 receptors. However, its effects on cardiomyocytes and blood vessels specifically required the MrgD receptor, distinguishing it from other renin-angiotensin system peptides.","whyItMatters":"The renin-angiotensin system is one of the most important peptide cascades in human physiology, controlling blood pressure, fluid balance, and cardiovascular function. Discovering a completely new bioactive peptide within this well-studied system is remarkable. Ala-(1-5) lowers blood pressure through mechanisms distinct from existing RAS peptides, potentially opening new therapeutic avenues for hypertension that target a previously unknown pathway.","specificNumbers":"~6-hour antihypertensive effect · acts through Mas, MrgD, and AT2 receptors · MrgD required for cardiac and vascular effects · present in human and rodent circulation","methodology":"The researchers used an extensive array of techniques: mass spectrometry (MALDI/TOF/TOF and LC-MS/MS) to identify and confirm the peptide in blood; isolated blood vessels and perfused hearts to test cardiovascular effects; isolated cardiomyocytes for contractility measurements; blood pressure recording in freely moving normotensive and hypertensive rats; echocardiography; central brain administration; cell culture experiments with receptor-transfected cells; and knockout mice lacking Mas, MrgD, or AT2 receptors to determine which receptors mediate the peptide's effects.","limitations":"This is primarily animal and cell-based research. While Ala-(1-5) was detected in human blood, all functional studies were conducted in rodents and cell lines. The blood pressure-lowering effects, cardiovascular actions, and receptor mechanisms need to be confirmed in humans before any clinical relevance can be established."},{"rthcId":"RPEP-16059","title":"Antimicrobial nanocoatings and films for contact lenses: progress and promise.","authors":"Sara, Manjulatha; Attard, Samuel; Kumar, Naresh; Willcox, Mark","year":2026,"journal":"Nanomedicine (London, England), 21(5), 683-690","doi":"10.1080/17435889.2026.2623930","pmid":"41607352","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Antimicrobial nanocoatings for contact lenses — including antimicrobial peptides like melimine and Mel4, metallic nanoparticles, polymeric layers, and hybrid systems — can achieve greater than 3-log10 (99.9%) bacterial reductions and have reduced corneal infiltrative events in clinical trials. AMPs and peptidomimetics are among the most promising approaches, preventing microbial adhesion and biofilm formation while maintaining lens biocompatibility. The field is moving toward hybrid, stimuli-responsive coatings that activate only under infection-specific conditions.","whyItMatters":"Microbial keratitis from contact lens wear affects 2-24 per 10,000 wearers annually and can cause permanent vision loss. With increasing contact lens use — especially for myopia control in children — safer lens designs are urgently needed. Antimicrobial peptide coatings offer a particularly attractive solution because they fight infections through mechanisms that bacteria are unlikely to develop resistance against, unlike conventional antibiotics.","specificNumbers":"","methodology":"Systematic literature review analyzing publications from PubMed, Scopus, and Web of Science (2008-2025). The review covers metallic nanoparticle coatings (silver, zinc oxide, titanium dioxide), organo-selenium coatings, polymeric layers, antimicrobial peptides (melimine, Mel4), and peptidomimetics. Key topics include coating techniques (surface grafting, dip-coating, plasma treatment), antimicrobial mechanisms, and outcomes from both preclinical and clinical trials.","limitations":"Several challenges remain: nanoparticle toxicity at certain concentrations, peptide degradation over the lens wear period, regulatory hurdles for novel coated medical devices, and the need for long-term safety data. Most coatings have been tested primarily against Gram-positive and Gram-negative bacteria, with less evidence against fungal or Acanthamoeba keratitis. Manufacturing scalability and cost for peptide-coated lenses are not fully addressed."},{"rthcId":"RPEP-16060","title":"GLP-1R agonists: recent advances, current gaps, and future challenges.","authors":"Saran, Anukriti; Raisinghani, Riya; Paliwal, Sarvesh; Sharma, Swapnil","year":2026,"journal":"Molecular diversity, 30(1), 101-112","doi":"10.1007/s11030-025-11195-6","pmid":"40301134","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16061","title":"Gut Microbiota and Metabolic Health: From Dysbiosis to Therapeutics.","authors":"Sasidharan Pillai, Sabitha; Ashraf, Ambika P","year":2026,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders","doi":"10.1007/s13300-026-01851-x","pmid":"41762381","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16062","title":"Semaglutide and Early-Stage Metabolic Abnormalities in Individuals With Schizophrenia Spectrum Disorders: A Randomized Clinical Trial.","authors":"Sass, Marie R; Klausen, Mette Kruse; Schwarz, Christine R; Rasmussen, Line; Giver, Malte E B; Hviid, Malthe; Schilling, Christoffer; Zamorski, Alexandra; Jensen, Andreas; Gefke, Maria; Storgaard, Heidi; Oturai, Peter S; Kjaer, Andreas; Hartmann, Bolette; Holst, Jens J; Ekstrøm, Claus T; Vinberg, Maj; Correll, Christoph U; Vilsbøll, Tina; Fink-Jensen, Anders","year":2026,"journal":"JAMA psychiatry, 83(2), 128-138","doi":"10.1001/jamapsychiatry.2025.3639","pmid":"41335431","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide 1 mg weekly for 26 weeks significantly improved HbA1c compared to placebo (mean difference -0.25%, p<0.001) in people with schizophrenia spectrum disorders on clozapine or olanzapine. 43% of semaglutide-treated participants achieved low-risk HbA1c levels (<5.4%) versus only 3% on placebo. Semaglutide also produced significant weight loss (-9.2 kg, p<0.001), waist circumference reduction (-7.0 cm, p<0.001), and fat mass reduction (-6.1 kg, p=0.006). Crucially, psychiatric symptoms did not worsen, and psychiatric adverse events were similar across groups. GI side effects were common but mild and transient.","whyItMatters":"People with schizophrenia die 15-20 years earlier than the general population, largely from cardiovascular disease driven by antipsychotic-induced weight gain and metabolic abnormalities. Clozapine and olanzapine — the most effective antipsychotics — are also the worst metabolic offenders. This JAMA Psychiatry trial shows semaglutide can safely reverse early metabolic damage without worsening psychiatric symptoms, potentially saving lives in one of medicine's most vulnerable populations.","specificNumbers":"n=73 randomized, 57 completed · 26 weeks · HbA1c: -0.25% vs. placebo (p<0.001) · 43% vs. 3% reached HbA1c <5.4% · Weight: -9.2 kg (p<0.001) · Waist: -7.0 cm (p<0.001) · Fat mass: -6.1 kg (p=0.006) · No psychiatric worsening","methodology":"Multicenter, double-blind, placebo-controlled, randomized clinical trial at 3 sites in Denmark (September 2021-August 2024). 73 participants aged 18-65 with schizophrenia spectrum disorders on clozapine or olanzapine (started within past 5 years) with early glycemic abnormalities (HbA1c 5.4-7.4%). Weekly subcutaneous semaglutide 1 mg or placebo for 26 weeks. Primary outcome: change in HbA1c at week 26. ITT analysis.","limitations":"Modest sample size (73 randomized, 57 completed — 22% dropout). Secondary outcomes were exploratory only. The 26-week duration may be too short to assess long-term metabolic and cardiovascular outcomes. Only clozapine and olanzapine users were included — results may differ for other antipsychotics. No lipid, liver function, or blood pressure benefits were observed, suggesting a longer trial may be needed for these endpoints."},{"rthcId":"RPEP-16063","title":"Semaglutide and Early-Stage Metabolic Abnormalities in Individuals With Schizophrenia Spectrum Disorders: A Randomized Clinical Trial.","authors":"Sass, Marie R; Klausen, Mette Kruse; Schwarz, Christine R; Rasmussen, Line; Giver, Malte E B; Hviid, Malthe; Schilling, Christoffer; Zamorski, Alexandra; Jensen, Andreas; Gefke, Maria; Storgaard, Heidi; Oturai, Peter S; Kjaer, Andreas; Hartmann, Bolette; Holst, Jens J; Ekstrøm, Claus T; Vinberg, Maj; Correll, Christoph U; Vilsbøll, Tina; Fink-Jensen, Anders","year":2026,"journal":"JAMA psychiatry, 83(2), 128-138","doi":"10.1001/jamapsychiatry.2025.3639","pmid":"41335431","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16064","title":"Associations Between Serum N-Terminal Pro-Brain Natriuretic Peptide Levels and the Prevalence of Sarcopenia in Middle-Aged and Older Japanese Adults: A Population-Based Cross-Sectional Study.","authors":"Sato, Ren; Yamagishi, Kazumasa; Jinnouchi, Hiroshige; Muraki, Isao; Yasuoka, Mikako; Kakihana, Hironobu; Kubo, Sachimi; Kihara, Tomomi; Matsumura, Takumi; Takada, Midori; Shimizu, Yuji; Ohira, Tetsuya; Tanigawa, Takeshi; Imano, Hironori; Iso, Hiroyasu","year":2026,"journal":"Geriatrics & gerontology international, 26(2), e70404","doi":"10.1111/ggi.70404","pmid":"41692421","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16065","title":"Tirzepatide and change in uric acid and its association with weight reduction: post hoc analyses of the SURMOUNT-1 randomised placebo-controlled trial.","authors":"Sattar, Naveed; Scilletta, Sabrina; Stefanski, Adam; Wang, Hui; Daly, Jack W; Linetzky, Bruno","year":2026,"journal":"Annals of the rheumatic diseases, 85(3), 558-565","doi":"10.1016/j.ard.2025.10.009","pmid":"41198460","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tirzepatide treatment over 72 weeks significantly reduced serum uric acid (SUA) at all three dose levels compared to placebo in the SURMOUNT-1 trial of 2,539 adults with obesity. At week 72, SUA decreased by -0.69 mg/dL (5 mg), -0.92 mg/dL (10 mg), and -0.95 mg/dL (15 mg) versus -0.18 mg/dL with placebo (all p<0.001). Reductions were significant regardless of baseline uric acid level or BMI. Mediation analysis showed that weight reduction explained 72.7% of the SUA decrease, suggesting the effect is primarily driven by weight loss (up to 20.9% body weight reduction).","whyItMatters":"Elevated uric acid causes gout — a painful inflammatory arthritis that frequently co-occurs with obesity. Current gout treatments focus on lowering uric acid with drugs like allopurinol, but they don't address the underlying obesity. Tirzepatide's ability to meaningfully reduce uric acid through weight loss suggests it could help prevent gout flares while simultaneously treating obesity — addressing the root cause rather than just the symptom.","specificNumbers":"n=2,539 · 72 weeks · Weight loss up to 20.9% · SUA change: -0.69 (5mg), -0.92 (10mg), -0.95 mg/dL (15mg) vs. -0.18 placebo · All p<0.001 · 72.7% mediated by weight loss","methodology":"Post hoc analysis of the SURMOUNT-1 randomized, double-blind, placebo-controlled trial. Adults with BMI ≥30 (or ≥27 with complications) were randomized to tirzepatide 5, 10, or 15 mg or placebo for 72 weeks. Serum uric acid was measured at baseline and multiple time points. Changes were analyzed across dose groups, baseline SUA quartiles, and baseline BMI categories. Mediation analysis quantified how much of the SUA reduction was explained by weight loss.","limitations":"This is a post hoc analysis — uric acid reduction was not a prespecified primary outcome of SURMOUNT-1. Participants were not selected for gout or hyperuricemia, so the clinical relevance for gout patients specifically is uncertain. The study did not measure gout flare rates. The remaining 27.3% of SUA reduction not explained by weight loss could reflect direct pharmacological effects, but this was not further investigated."},{"rthcId":"RPEP-16066","title":"Established and emerging pharmacologic options and unmet need in HFpEF and HFmrEF.","authors":"Sauer, Andrew J; Ter Maaten, Jozine M; Savarese, Gianluigi","year":2026,"journal":"ESC heart failure","doi":"10.1093/eschf/xvag056","pmid":"41711220","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16067","title":"Two Cases of Diabetes Remission through Temporary Tirzepatide Treatment.","authors":"Sawamura, Toshitaka; Ohmori, Ai; Kometani, Mitsuhiro; Karashima, Shigehiro; Yoneda, Takashi","year":2026,"journal":"Internal medicine (Tokyo, Japan), 65(5), 666-672","doi":"10.2169/internalmedicine.5779-25","pmid":"40803851","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16068","title":"Use (and Potential for Abuse) of Glucagon-Like Peptide-1 Medications Among Individuals with Eating Disorders: Empirical Review and Clinical Guidance.","authors":"Schaefer, Lauren M; Kerver, Gail A; Allison, Kelly C; Kohoutek, Bradley; Steffen, Kristine J","year":2026,"journal":"The Psychiatric clinics of North America, 49(1), 183-202","doi":"10.1016/j.psc.2025.08.013","pmid":"41708263","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16069","title":"GLP-1-derived therapies and sarcopenia: plea for a specific focus on at risk special populations.","authors":"Scheen, André J","year":2026,"journal":"Diabetes & metabolism, 52(1), 101708","doi":"10.1016/j.diabet.2025.101708","pmid":"41101588","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16070","title":"Baseline characteristics from evoke and evoke+: Two phase 3 randomized placebo-controlled trials of semaglutide in participants with early-stage symptomatic Alzheimer's disease.","authors":"Scheltens, Philip; Atri, Alireza; Feldman, Howard H; Zetterberg, Henrik; Sano, Mary; Johannsen, Peter; Colombo, Teresa León; Bardtrum, Lars; Jeppesen, Rose; Hansen, Charlotte T; Cummings, Jeffrey L","year":2026,"journal":"Alzheimer's & dementia (New York, N. Y.), 12(1), e70200","doi":"10.1002/trc2.70200","pmid":"41522368","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16071","title":"Exposure-Response Modeling of Monthly Migraine Days for Efficacy of Atogepant in Patients With Episodic or Chronic Migraine.","authors":"Schlachter, Louisa; Beck, Denise; Boinpally, Ramesh R; Stodtmann, Sven","year":2026,"journal":"CPT: pharmacometrics & systems pharmacology, 15(1), e70154","doi":"10.1002/psp4.70154","pmid":"41272937","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16072","title":"Population Pharmacokinetics of Atogepant for the Prevention of Migraine.","authors":"Schlachter, Louisa; Stodtmann, Sven; Voelkner, Alexander; Jonsson, Fredrik; Lagraauw, Hendrik Maxime; Boinpally, Ramesh R","year":2026,"journal":"Clinical pharmacokinetics, 65(1), 149-164","doi":"10.1007/s40262-025-01566-5","pmid":"41222899","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16073","title":"Spatial microenvironments tune immune response dynamics in the Drosophila larval fat body.","authors":"Schlomann, Brandon H; Pai, Ting-Wei; Sandhu, Jazmin; Ferrer Imbert, Genesis; Graham, Thomas G W; Garcia, Hernan G","year":2026,"journal":"PLoS genetics, 22(2), e1012029","doi":"10.1371/journal.pgen.1012029","pmid":"41632823","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Individual fat body cells expressed antimicrobial peptides at approximately constant rates following infection, but the average rate varied along the anterior-posterior axis — rapid expression in anterior and posterior lobes, slower in the middle. These tissue microenvironments were predefined independently of infection, with the rate-limiting step of AMP induction occurring downstream of peptidoglycan sensing.\n\nThe spatial distribution of immune-active microenvironments correlated with heartbeat-dependent fluid flow patterns, paralleling the strategic positioning of immune cells (e.g., Kupffer cells in liver sinusoids) in mammalian organs. Overexpression experiments confirmed that immune signaling capacity varies by position, not just exposure to pathogens.","whyItMatters":"Spatial organization of immune responses is a fundamental but poorly understood aspect of immunity. This study reveals that even in a simple organism like Drosophila, antimicrobial peptide production is not random — it's spatially organized to maximize efficiency. Understanding these design principles could inform strategies for boosting targeted antimicrobial peptide production in humans and explain why certain tissues are more or less susceptible to infection.","specificNumbers":"","methodology":"Light sheet fluorescence microscopy of whole, live Drosophila larvae was developed to quantify single-cell antimicrobial peptide expression dynamics in real time. Spatial transcriptomic analysis mapped gene expression patterns across the fat body. Overexpression of immune signaling components was used to test whether spatial differences were predefined or infection-induced. Fluid flow patterns were characterized and correlated with immune microenvironment locations.","limitations":"This is a Drosophila study — the fly fat body is functionally analogous to the mammalian liver but structurally simpler. The correlation with fluid flow patterns is suggestive but not proven to be causal. The study examined antimicrobial peptide expression dynamics but did not assess whether the spatial patterns translate to differences in actual pathogen killing. Only bacterial infection (peptidoglycan-triggered) was studied."},{"rthcId":"RPEP-16074","title":"Targeted nanoparticles for placenta-specific drug delivery in pregnant rhesus macaques.","authors":"Schmidt, Jenna K; Mitzey, Ann M; Keding, Logan T; Shaw, Sarah A; Renshall, Lewis; Beards, Frances; Al-Mugotir, Mona H; Simmons, Heather A; Basu, Puja; Schotzko, Michele L; Ren, Emily; Golos, Thaddeus G; Harris, Lynda K","year":2026,"journal":"Theranostics, 16(5), 2118-2135","doi":"10.7150/thno.115081","pmid":"41424845","tags":[],"studyType":"in-vivo","evidenceStrength":"moderate","keyFinding":"Liposomes decorated with the iRGD homing peptide (CRGDKGPDC) selectively accumulated in the placentas of pregnant rhesus macaques — without crossing to the fetus. This is a critical proof-of-concept: a peptide-guided nanoparticle can deliver drug payloads specifically to the placenta in a primate model closely resembling human pregnancy.\n\nThe iRGD-targeted liposomes were well tolerated with no adverse clinical reactions, no abnormal placental or fetal pathology, and stable maternal blood markers. Importantly, non-targeted (ARA peptide) liposomes showed widespread distribution to both maternal and fetal tissues — demonstrating that the iRGD peptide targeting is what prevents fetal exposure. The approach worked at both early gestation (days 45-64) and mid-gestation (days 84-100).","whyItMatters":"Treating pregnancy complications like preeclampsia and fetal growth restriction has been nearly impossible because any drug given to the mother also reaches the developing fetus. This peptide-targeted nanoparticle approach solves that problem by delivering drugs exclusively to the placenta. Moving from mice to rhesus macaques — whose placentas closely resemble human placentas — is a major translational milestone that brings this technology significantly closer to human clinical trials.","specificNumbers":"n=11 pregnant rhesus macaques (8 iRGD, 3 ARA control) · iRGD peptide: CRGDKGPDC · Early gestation: days 45-64 · Mid-gestation: days 84-100 · Term = 165 days · No fetal transfer with iRGD · No adverse reactions · 24-hour tissue collection","methodology":"Researchers produced liposomes using the thin-film method, decorating them with either the placenta-homing peptide iRGD (CRGDKGPDC) or a non-targeting control peptide ARA (ARALPSQRSR), and loaded them with a fluorescent tracer. These were infused intravenously into pregnant rhesus macaques at two gestational timepoints. After 24 hours, maternal blood and tissues from the mother, placenta, and fetus were collected and examined for fluorescent signal, while blood markers and organ pathology were assessed for safety.","limitations":"Very small sample size (11 animals total, with only 1-4 per condition). The study used a fluorescent tracer rather than an actual therapeutic drug, so drug-specific effects can't be assessed. Only a 24-hour observation window was used — longer-term safety, repeated dosing, and effects on pregnancy outcomes weren't evaluated. Rhesus macaque placentas, while similar to human placentas, are not identical."},{"rthcId":"RPEP-16075","title":"Tirzepatide on physical function in adults with overweight or obesity: A systematic review and meta-analysis.","authors":"Schmidt, Pedro Henrique Siedschlag; de Souza, Vitor Sodré Nonato; Machado, Luís Guilherme; Rodrigues, João Vitor Ahlf; da Cruz, João Victor Ramos; de Souza, Lis Sodré Nonato; Dos Santos, Bruno Eulálio; Hohl, Alexandre; Ronsoni, Marcelo Fernando; van de Sande-Lee, Simone","year":2026,"journal":"Diabetes, obesity & metabolism","doi":"10.1111/dom.70529","pmid":"41705736","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tirzepatide significantly improved physical function compared to placebo on both primary outcome measures: SF-36 physical function domain (MD 2.26 points; 95% CI 1.76-2.76) and IWQOL-Lite-CT physical function subscale. Both the 10 mg and 15 mg weekly doses showed consistent benefits in subgroup analyses.\n\nHowever, between-study heterogeneity was extremely high (I² = 99.8%), which limits the interpretability of pooled estimates. The overall certainty of evidence was rated as moderate by GRADE criteria due to risk of bias and inconsistency across studies.","whyItMatters":"Obesity significantly impairs physical function and quality of life, but weight loss drugs are often evaluated only on weight and metabolic outcomes. This meta-analysis demonstrates that tirzepatide's benefits extend beyond the scale — patients actually feel and function better physically. This is important for justifying the clinical value and cost of these medications, as physical function directly impacts daily life, independence, and overall wellbeing.","specificNumbers":"","methodology":"Systematic review and meta-analysis of randomized controlled trials found through PubMed, Embase, and Cochrane Library searches up to July 2025. Included RCTs compared once-weekly tirzepatide (10 or 15 mg) with placebo and reported validated physical function outcomes. Random-effects models calculated pooled mean differences with 95% confidence intervals. Evidence quality was assessed using GRADE methodology.","limitations":"The extremely high between-study heterogeneity (I² = 99.8%) is a major limitation that makes the pooled estimates difficult to interpret definitively. This variability may reflect differences in patient populations, comorbidities, or study designs across the 6 RCTs. The GRADE certainty was moderate due to risk of bias and inconsistency. Physical function was a secondary outcome in the original trials, not their primary endpoint."},{"rthcId":"RPEP-16076","title":"A Review of First-Generation Obesity Medications.","authors":"Schmitz, Sarah H; Saunders, Katherine H","year":2026,"journal":"Current atherosclerosis reports, 28(1), 14","doi":"10.1007/s11883-026-01389-0","pmid":"41569475","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"First-generation obesity medications — phentermine, orlistat, phentermine/topiramate ER, bupropion/naltrexone SR, and liraglutide 3.0 mg — remain effective and clinically relevant despite the arrival of newer incretin-based therapies. While their average weight loss is lower than next-generation drugs, clinical trial data show that a substantial proportion of patients on these agents achieve 10% or more total body weight loss. The review emphasizes these medications as cost-effective, evidence-based tools for managing obesity-related atherosclerosis and other cardiometabolic complications.","whyItMatters":"With newer GLP-1 drugs dominating headlines, older obesity medications risk being overlooked — even though they remain affordable, accessible, and effective for many patients. This review reminds clinicians that first-generation agents, including the peptide-based liraglutide, still have a critical role in comprehensive obesity care, especially where cost or access to newer drugs is a barrier.","specificNumbers":"","methodology":"Narrative review of pharmacologic profiles, clinical trial evidence, and practical considerations for five first-generation obesity medications.","limitations":"As a narrative review, this paper does not present new clinical data or perform a systematic analysis. Findings are limited to summarizing existing trial evidence without meta-analytic pooling."},{"rthcId":"RPEP-16077","title":"Computational Design, Synthesis, and Evaluation of Stapled Peptide-Based Antagonists of the CGRP Receptor.","authors":"Schofield, Adam L; Notari, Evangelia; Rožňovcová, Mária; Cox, Kathryn W; D'Aloisio, Vera; Steuer, Christian; Michel, Julien; Cottrell, Graeme S; Coxon, Christopher R","year":2026,"journal":"Journal of medicinal chemistry","doi":"10.1021/acs.jmedchem.5c03445","pmid":"41789660","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16078","title":"Immune checkpoint inhibition increases antigen-specific T cell response in head and neck cancer.","authors":"Schuler, Patrick J; Oliveri, Franziska; Puntigam, Lisa; Six, Klara; Kaißer, Carlotta; Maier, Julia; Laban, Simon; von Witzleben, Adrian; Brunner, Cornelia; Messerer, David A C; Schrezenmeier, Hubert; Hoffmann, Thomas K; Goetz, Marlies; Greiner, Jochen","year":2026,"journal":"Scientific reports, 16(1), 5583","doi":"10.1038/s41598-026-38740-z","pmid":"41663641","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Using mixed lymphocyte-peptide cultures, researchers generated antigen-specific cytotoxic T cells against several tumor-associated antigens, with MAGE, PRAME, and NY-ESO-1 identified as the most potent immunostimulatory peptide targets. When these peptide-specific T cells were co-cultured with head and neck cancer cell lines in the presence of anti-PD-1 antibody, the antigen-specific immune response was significantly increased compared to T cells without checkpoint blockade.\n\nHowever, combining anti-PD-1 with other checkpoint inhibitors targeting LAG-3 or TIM-3 produced little or no synergistic enhancement, suggesting that PD-1 is the primary checkpoint restraining peptide-specific anti-tumor immunity in this cancer type.","whyItMatters":"With only a 20% response rate to checkpoint inhibitors alone, most head and neck cancer patients need better treatment options. This study suggests that peptide vaccines targeting tumor antigens could prime the immune system, and checkpoint inhibitors could then remove the brakes, creating a more powerful combined attack. This personalized immunotherapy approach could significantly expand the number of patients who benefit from treatment.","specificNumbers":"","methodology":"Researchers used mixed lymphocyte-peptide cultures to generate antigen-specific cytotoxic T cells from healthy donors against various tumor-associated peptide antigens. The immune response of these T cells against head and neck squamous cell carcinoma (HNSCC) cell lines was measured using ELISPOT assays. The influence of PD-1 blockade, alone and in combination with LAG-3 and TIM-3 inhibitors, on peptide-specific immune responses was tested in co-culture systems with tumor cells.","limitations":"This is an in vitro study using T cells from healthy donors rather than cancer patients, whose immune systems may be more suppressed. The results in laboratory cell cultures may not directly translate to clinical outcomes. The study did not test these combinations in animal models or clinical trials. The specific peptide antigens used may not be expressed by all head and neck tumors, limiting the generalizability of the vaccination approach."},{"rthcId":"RPEP-16079","title":"Evaluation of resensibilization in flaps containing sensory nerves in the animal model: A systematic review of the literature.","authors":"Schulz, Stephanie N; Triolo, Julie; André-Lévigne, Dominik; Kalbermatten, Daniel F; Madduri, Srinivas; Engels, Patricia E","year":2026,"journal":"Journal of plastic, reconstructive & aesthetic surgery : JPRAS, 113, 652-667","doi":"10.1016/j.bjps.2025.12.003","pmid":"41506218","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16080","title":"Single Amino Acid Modulates Antimicrobial Peptide Cooperativity between LL-37 and HNP1.","authors":"Schwitter, Ariane M; Yasuda, Takashi; Li, Xiang; Sugihara, Kaori","year":2026,"journal":"Langmuir : the ACS journal of surfaces and colloids, 42(3), 2423-2430","doi":"10.1021/acs.langmuir.5c04387","pmid":"41536269","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16081","title":"The pathway-independent positive allosteric modulator C1 allows for the identification of active Y4 receptor relevant positions.","authors":"Schüß, Corinna; Vu, Oanh; Pelczyk, Tim; Schubert, Mario; Du, Yu; Stichel, Jan; Weaver, C David; Meiler, Jens; Beck-Sickinger, Annette G","year":2026,"journal":"Cellular and molecular life sciences : CMLS, 83(1), 74","doi":"10.1007/s00018-025-06019-7","pmid":"41528432","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16082","title":"Thyroid Cancer Risk in Patients With Type 2 Diabetes Taking Glucagon-Like Peptide 1 Receptor Agonists.","authors":"Sciscent, Bao Y; Eberly, Hanel W; Lorenz, F Jeffrey; Goldrich, David; Goyal, Neerav; Goldenberg, David","year":2026,"journal":"OTO open, 10(1), e70188","doi":"10.1002/oto2.70188","pmid":"41523888","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Patients with type 2 diabetes taking GLP-1 receptor agonists showed no statistically significant increase in 5-year thyroid cancer risk compared to those taking three other common diabetes drug classes.\n\nGLP-1RA vs SGLT-2 inhibitors (7,736 per group): thyroid cancer rate 0.30% vs 0.48%, RR 0.62 (95% CI 0.37–1.05, P=.07). GLP-1RA vs metformin (5,158 per group): 0.25% vs 0.39%, RR 0.65 (95% CI 0.32–1.31, P=.22). GLP-1RA vs DPP-4 inhibitors (12,570 per group): 0.33% vs 0.37%, RR 0.91 (95% CI 0.60–1.39, P=.67).\n\nIn all three comparisons, thyroid cancer rates were numerically lower in the GLP-1RA group, though none reached statistical significance.","whyItMatters":"Millions of people now take GLP-1 receptor agonists for diabetes and weight loss, and thyroid cancer has been a safety concern flagged in animal studies and drug labels. This large real-world study provides reassuring evidence that these widely prescribed medications may not increase thyroid cancer risk over five years, though longer follow-up is still needed.","specificNumbers":"","methodology":"This was a retrospective cohort study using the TriNetX database, identifying type 2 diabetes patients between 2017 and 2019. Researchers compared thyroid cancer rates over 5 years between patients taking GLP-1 receptor agonists and those taking three alternative diabetes medications (SGLT-2 inhibitors, metformin, and DPP-4 inhibitors). Propensity score matching was used to control for differences in demographics and comorbidities between groups.","limitations":"As a retrospective database study, it cannot establish causation. The 5-year follow-up may be too short to detect cancers with long latency periods. The TriNetX database may have coding inconsistencies or missing data. Most GLP-1 receptor agonists were approved within the last decade, so long-term effects beyond 5 years remain unknown. The study also could not distinguish between specific GLP-1RA drugs or account for duration of use."},{"rthcId":"RPEP-16083","title":"Gut enteroendocrine cell activation using a combination of GPR119 and GPR40 agonists results in synergistic hormone secretion in mice and humans.","authors":"Sebhat, Iyassu K; Murphy, Monika J M; Zheng, Shuqin; Lovelett, Robert J; Engelstoft, Maja; Kosinski, Daniel; Yang, Xiaodong; Dunn, Victoria; Whang, John; Lombardo, Maximilian G; Heilbut, Adrian; Terracina, Giuseppe; Nicholas, Nicole; Leitner, Molly; Consolati, Matthew J; Chan, Bryan; Poterewicz, Gregory; Vance, Annemarie; Liu, Jiajun; Weber, Ann E; Lauring, Brett; Thornberry, Nancy; Pinto, Shirly","year":2026,"journal":"Cell metabolism, 38(1), 50-64.e12","doi":"10.1016/j.cmet.2025.11.001","pmid":"41338185","tags":[],"studyType":"Preclinical + Phase 1 Human Trial","evidenceStrength":"Moderate-High","keyFinding":"Researchers developed oral drugs (K-757 and K-833) that directly target gut enteroendocrine cells via GPR40 and GPR119 receptors to trigger massive release of natural satiety hormones including GLP-1 — essentially mimicking what bariatric surgery does to the gut.\n\nThe combination of both receptor agonists produced synergistic hormone secretion in both mouse and human gut tissue (enteroids). In mice, the combination improved glucose tolerance and promoted weight loss. Most remarkably, in phase 1 human trials, the circulating gut hormone levels achieved EXCEEDED those seen after bariatric surgery — suggesting these oral pills could potentially replicate the metabolic benefits of surgery without the knife.","whyItMatters":"Bariatric surgery is the most effective treatment for severe obesity, producing dramatic and sustained weight loss partly through supraphysiologic activation of gut hormone cells. But surgery is invasive, irreversible, and accessible to only a fraction of eligible patients. This study demonstrates that oral drugs can activate the same gut cells to produce even higher hormone levels than surgery — a completely different approach from injectable GLP-1 drugs like semaglutide that flood the body with synthetic hormone. If confirmed, this could represent a paradigm shift: 'bariatric surgery in a pill.'","specificNumbers":"GPR40 + GPR119 dual agonism · Synergistic hormone secretion in enteroids · Weight loss + glucose improvement in mice · Phase 1 human hormone levels exceeded bariatric surgery levels · Gut-targeted oral administration","methodology":"The team first used advanced single-cell technologies to map gut enteroendocrine cell diversity, identifying cells that co-express satiety hormones and GPR40/GPR119 receptors. They developed gut-targeted agonists (K-757 for GPR119 and K-833 for GPR40) and tested them in mouse and human enteroids (miniature gut organoids), then in live mice for weight and glucose outcomes. The compounds were then advanced to phase 1 human trials measuring circulating gut hormone levels.","limitations":"Weight loss and glucose tolerance data are from mice only — human efficacy data (weight loss, appetite reduction) are not yet available. Phase 1 data showed hormone elevation but clinical outcomes require phase 2/3 trials. The gut-targeting strategy's long-term safety is unknown. Whether supraphysiologic hormone levels sustained over time would cause adverse effects (as seen with some GLP-1 drugs) needs investigation."},{"rthcId":"RPEP-16084","title":"GLP-1 Receptor Agonists for Secondary Prevention After Myocardial Infarction and Stroke in Type 2 Diabetes: Nationwide Real-World Evidence.","authors":"Sedova, Petra; Vrablík, Michal; Kala, Petr; Ošťádal, Petr; Tichopád, Aleš; Tomek, Aleš; Mikulik, Robert; Donin, Gleb; Littnerová, Simona; Kent, Julia Anna; Jarkovsky, Jiří; Somers, Virend K; Brown, Robert D","year":2026,"journal":"European journal of preventive cardiology","doi":"10.1093/eurjpc/zwag002","pmid":"41499432","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16085","title":"Comparative pharmacovigilance analysis of suicidality-related adverse events among GLP-1 and non-GLP-1 anti-obesity drugs in the FDA Adverse Event Reporting System.","authors":"Seijas-Amigo, Jose; Salgado-Barreira, Ángel; Rodriguez-Penas, Diego; Cardeso-Paredes, Begoña; Ribeiro-Ferreiro, Marta; Rodriguez-Mañero, Moisés; Gonzalez-Juanatey, Jose Ramon","year":2026,"journal":"International journal of clinical pharmacy","doi":"10.1007/s11096-026-02099-y","pmid":"41739406","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16086","title":"Ischemic Colitis Associated With Tirzepatide Therapy in a Young Female Patient: A Case Report.","authors":"Sekhon, Simone; Kahlon, Ibaadat; Latson, William","year":2026,"journal":"Cureus, 18(1), e101437","doi":"10.7759/cureus.101437","pmid":"41694961","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16087","title":"Modeling Obesity and Weight Loss in Mice Using Novel AAV Approaches.","authors":"Sellers, Hunter G; Brown, Zachary L; Khalil, Noureen S; Haigh, Stephen B; Shivers, Mitchell A; Patel, Tej V; Joshua, Austin T; Weintraub, Neal L; Barman, Scott A; Belin de Chantemele, Eric J; Kirov, Sergei A; Stepp, David W; Fulton, David J R","year":2026,"journal":"Obesity (Silver Spring, Md.), 34(2), 417-427","doi":"10.1002/oby.70081","pmid":"41456932","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16088","title":"Astrocytes mediate a positive feedback loop for oxytocin.","authors":"Selles, Maria Clara; Cooper, Melissa L; Limone, Francesco; Ahmed, Araf; Liddelow, Shane A; Froemke, Robert C; Chao, Moses V","year":2026,"journal":"bioRxiv : the preprint server for biology","doi":"10.64898/2026.02.02.699227","pmid":"41676690","tags":[],"studyType":"animal","evidenceStrength":"preliminary","keyFinding":"Chronic social isolation in male mice reduced oxytocin peptide production and delayed the return of social huddling behavior when the mice were put back together. Exogenous oxytocin treatment prevented both the behavioral and molecular effects of isolation.\n\nThe key discovery: astrocytes (brain support cells) in the hypothalamus create a positive feedback loop for oxytocin. When oxytocin stimulates astrocytes, they produce retinoic acid (via the enzyme Aldh1a1), which in turn stimulates more oxytocin production. This means astrocytes act as sensors and amplifiers of neuropeptide levels, directly influencing social behavior.","whyItMatters":"This study reveals a previously unknown mechanism by which the brain maintains oxytocin levels — through astrocytes rather than neurons alone. The finding that social isolation actually decreases oxytocin production (not just release) provides a biological explanation for how loneliness becomes self-reinforcing. It also suggests that astrocytes could be therapeutic targets for conditions involving social dysfunction, from autism to depression.","specificNumbers":"Chronic social isolation reduced oxytocin peptide production · exogenous oxytocin prevented isolation effects · Aldh1a1 enzyme upregulated in astrocytes · retinoic acid increased oxytocin expression","methodology":"Animal study in male mice using chronic social isolation paradigms, resocialization experiments (huddling behavior), exogenous oxytocin administration, conditional gene knockouts to dissect the astrocyte-mediated pathway, and molecular analysis of oxytocin expression and the retinoic acid signaling pathway (Aldh1a1) in hypothalamic astrocytes.","limitations":"This is a preprint (bioRxiv) that has not yet undergone peer review. The study was conducted only in male mice, so sex differences cannot be assessed. Mouse social behavior may not fully translate to human social cognition. The conditional knockout approach is powerful but may have off-target effects."},{"rthcId":"RPEP-16089","title":"Marine-derived antimicrobial peptides (AMPs): Blue biotechnological assets for sustainable healthcare and circular bioeconomy.","authors":"Selvaraj, Chandrabose; Desai, Deepali; Santos-Villalobos, Sergio de Los; Jayaprakashvel, Mani; Muthezhilan, Radhakrishnan; Singh, Sanjeev Kumar","year":2026,"journal":"Advances in protein chemistry and structural biology, 149, 171-201","doi":"10.1016/bs.apcsb.2025.08.002","pmid":"41581932","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Marine-derived antimicrobial peptides (AMPs), sourced from invertebrates, extremophiles, and cyanobacteria, exhibit broad-spectrum activity against drug-resistant pathogens through membrane disruption and immunomodulation. These cationic, amphipathic molecules show low resistance propensity and multifunctional bioactivity spanning antimicrobial, antioxidant, and anticancer properties. Advances in machine learning, genomic/metagenomic tools, and synthetic biology are revolutionizing AMP discovery and optimization. Biotechnological innovations in heterologous expression and marine biomass valorization support scalable production aligned with circular economy principles.","whyItMatters":"Antimicrobial resistance (AMR) is projected to cause 10 million deaths annually by 2050. Marine organisms are an underexplored reservoir of antimicrobial peptides that have evolved over billions of years to combat pathogens in one of Earth's most microbially diverse environments. Their unique structural features — shaped by extreme ocean conditions — give them properties that land-derived peptides often lack, making them promising candidates for next-generation anti-infective drugs.","specificNumbers":"Sources: invertebrates, extremophiles, cyanobacteria · Broad-spectrum activity · Low resistance propensity · Multifunctional: antimicrobial + antioxidant + anticancer · Applications: healthcare, aquaculture, food safety, environmental remediation","methodology":"Comprehensive review covering the discovery, structural features, mechanisms of action, biotechnological production, and applications of marine-derived AMPs. Discusses genomic/metagenomic mining, machine learning-based peptide prediction, synthetic biology approaches, and circular bioeconomy frameworks for sustainable commercialization.","limitations":"As a review, no new experimental data is presented. The abstract acknowledges critical challenges including production scalability, regulatory frameworks, and the gap between laboratory discovery and commercial application. Many marine AMPs described in the literature have not progressed beyond in vitro characterization."},{"rthcId":"RPEP-16090","title":"Molecular landscape connecting complications of dry eye disease: mechanisms, therapeutic targets, biomarkers, and future innovations.","authors":"Sen, Himeshwer; Durgapal, Sumit; Jakhmola, Vikas","year":2026,"journal":"International ophthalmology, 46(1), 97","doi":"10.1007/s10792-026-03940-z","pmid":"41627595","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16091","title":"Targeting drug resistance in colorectal cancer using peptide-based scaffolds: new frontiers in colorectal cancer therapy.","authors":"Sen, Sanjukta; Mitra, Sreemoyee; Karati, Dipanjan","year":2026,"journal":"Nanomedicine (London, England), 21(5), 691-703","doi":"10.1080/17435889.2026.2628241","pmid":"41674360","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies several peptide-based strategies showing preclinical promise against drug-resistant colorectal cancer. Peptide-drug conjugates enhance targeted delivery and antitumor effects. Cell-penetrating peptides improve drug uptake into resistant cells. Pro-apoptotic and oncolytic peptides directly induce tumor cell death through mechanisms that bypass standard resistance pathways.\n\nPeptides can also target multiple resistance mechanisms including DNA repair, cell cycle arrest, apoptosis evasion, gene expression changes, and the tumor microenvironment. The authors introduce a Mechanistic Resistance Profiling (MRP) Framework that classifies peptides by the specific resistance layer they target (efflux, repair, apoptosis, tumor microenvironment, and immune evasion) to guide rational combination therapies.","whyItMatters":"Colorectal cancer is a leading cause of cancer death, and drug resistance severely limits treatment effectiveness. Peptide-based approaches offer a versatile toolkit for attacking resistance through multiple mechanisms simultaneously. If validated clinically, these strategies could restore treatment sensitivity in patients whose cancers have stopped responding to conventional therapies.","specificNumbers":"","methodology":"This is a narrative review article that synthesizes recent research on peptide-mediated therapies against drug-resistant colorectal cancer. The authors surveyed preclinical studies and clinical evaluations of peptide-drug conjugates, cell-penetrating peptides, pro-apoptotic peptides, oncolytic peptides, immunotherapeutic peptides, and peptide-nanocarrier systems.","limitations":"The evidence reviewed is primarily preclinical — most peptide-based strategies discussed have not been validated in human clinical trials. The proposed MRP Framework is a conceptual tool that needs clinical validation. Peptide stability, bioavailability, and manufacturing scalability remain practical challenges. The review does not quantify efficacy across studies with specific outcome data."},{"rthcId":"RPEP-16092","title":"Comparison of Pediatric and Adult Glucagon-Like Peptide-1 Receptor Agonist Exposures Reported To United States Poison Centers, 2017-2024.","authors":"Senthilkumar, Anjali; Hays, Hannah L; Kistamgari, Sandhya; Rine, Natalie I; Rhodes, Allison L; Gaw, Christopher E; Smith, Gary A","year":2026,"journal":"Journal of medical toxicology : official journal of the American College of Medical Toxicology","doi":"10.1007/s13181-026-01128-6","pmid":"41784916","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16093","title":"Can atogepant be a preventive treatment for cluster headache?-Insights from a case series.","authors":"Serrão, Catarina; Sotero, Filipa Dourado; Kauppila, Linda Azevedo; Martins, Isabel Pavão","year":2026,"journal":"Headache, 66(1), 336-340","doi":"10.1111/head.15066","pmid":"41044859","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16094","title":"Dual-functional urinary PVC catheters via peptide surface modification for the prevention of biofilm formation and fibrotic response in vitro.","authors":"Sezer, Buse; Bilgiç, Eda; Ercan, Utku Kürşat; Karaman, Ozan; Pulat, Günnur","year":2026,"journal":"Journal of materials chemistry. B, 14(7), 2190-2203","doi":"10.1039/d5tb02559a","pmid":"41660757","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16095","title":"Prolonged Semaglutide Treatment Reveals Stage-Dependent Changes to Feeding Behavior and Metabolic Adaptations in Male Mice.","authors":"Shah, Harsh; Ayala, Julio E","year":2026,"journal":"Diabetes, 75(2), 288-300","doi":"10.2337/db25-0678","pmid":"41329075","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16096","title":"Tirzepatide and Reduced Risk of Diabetic Retinopathy and Related Complications: A Multicenter U.S. Cohort Study.","authors":"Shah, Jaffer; Razavi, Peyman; Festok, Muhamad; Ahmed, Harris; Mahrous, M Abdallah; Kovacs, Kyle D; Kiss, Szilárd","year":2026,"journal":"Ophthalmology","doi":"10.1016/j.ophtha.2026.01.013","pmid":"41577258","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16097","title":"Roles and applications of peptide nucleic acid-loaded nanoparticles in cancer.","authors":"Shah, Natasha; Vedanayagam, Suganthi; Raymonde, Smith; Ramirez Garcia, Kevin; Eassa, Heba A; Gupta, Anisha","year":2026,"journal":"Nanomedicine (London, England), 21(6), 869-884","doi":"10.1080/17435889.2026.2628235","pmid":"41688131","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16098","title":"Addressing patient concerns about the 'newness' and long-term safety of GLP-1 receptor agonists: A clinician's guide to counseling.","authors":"Shah, Priyansh P; Bhattacharya, Romit","year":2026,"journal":"American journal of preventive cardiology, 26, 101418","doi":"10.1016/j.ajpc.2026.101418","pmid":"41608676","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 receptor agonists are far from experimental novelties — GLP-1 was first discovered in the 1980s, and these drugs have accumulated nearly two decades of clinical experience with millions of patient-years of safety data. Newer agents like semaglutide and tirzepatide use structural modifications that prolong the hormone's action without fundamentally changing its mechanism. Safety data consistently show that side effects are predominantly mild, transient gastrointestinal issues, with no confirmed evidence supporting feared risks such as cancer.","whyItMatters":"Patient reluctance to start GLP-1 medications due to perceived 'newness' is a real barrier to treatment, even as these drugs show significant benefits for diabetes, obesity, and cardiovascular health. By providing clinicians with concrete talking points grounded in the actual research timeline and safety record, this guide could help more patients access effective peptide-based therapies.","specificNumbers":"","methodology":"The authors wrote a clinical commentary synthesizing the history of GLP-1 research, comparing native GLP-1 to modern receptor agonists, and reviewing existing safety data. They developed a practical counseling checklist and sample patient-centered language to help clinicians facilitate informed decision-making conversations.","limitations":"This is a clinical commentary rather than a systematic review or original research study. It does not present new safety data but synthesizes existing information. The counseling strategies provided, while practical, have not been formally tested for effectiveness in improving patient adherence or reducing hesitancy."},{"rthcId":"RPEP-16099","title":"Cyclic Peptides in Wound Hydrogels: Current Advances and Future Directions.","authors":"Shahjad; Garg, Yashika; Kumar, Arun; Pathak, Neha; Chauhan, Bhumika; Nandi, Sisir","year":2026,"journal":"Current drug discovery technologies","doi":"10.2174/0115701638416002251126071556","pmid":"41588759","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16100","title":"Advancement in peptide-based therapeutics for the treatment of type 2 diabetes mellitus: current progress and future prospects.","authors":"Shahriar, Md Fahim; Kabir, Janisa; Kong, Yi","year":2026,"journal":"Molecular diversity","doi":"10.1007/s11030-025-11455-5","pmid":"41746526","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16101","title":"Efficacy and safety of CGRP monoclonal antibodies for migraine prevention in episodic migraine; a network Meta-analysis.","authors":"Shakir, Ishwa; Shahzad, Faizan; Shabbir, Ahsan; Shahabuddin, Saba; Shabbir, Haroon; Karamat, Sobia; Hulou, Saad; Khalid, Abdul Rauf; Ahmed, Syed Ijlal","year":2026,"journal":"European journal of clinical pharmacology, 82(2), 27","doi":"10.1007/s00228-025-03934-3","pmid":"41546694","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16102","title":"Oral delivery of liraglutide using CPP/hyaluronic acid-modified mesoporous silica nanoparticles: A virus-inspired strategy for intestinal absorption.","authors":"Shams, Narges; Esfandyari-Manesh, Mehdi; Sharifzadeh, Mohammad; Amini, Mohsen; Fatahi, Yousef; Dinarvand, Rassoul","year":2026,"journal":"Biomaterials advances, 182, 214714","doi":"10.1016/j.bioadv.2026.214714","pmid":"41604908","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16103","title":"Outcomes of obesity medications in those with low response to a low-energy diet meal replacement programme: An observational study.","authors":"Shand, James; Jiang, Yannan; Murphy, Rinki","year":2026,"journal":"Obesity pillars, 17, 100245","doi":"10.1016/j.obpill.2026.100245","pmid":"41551724","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16104","title":"Efficacy of rhBNP in heart failure with atrial fibrillation combined with poor conventional therapy response and recurrence risk factors.","authors":"Shang, Huijuan; Wang, Xiaojun; Shi, Xiaoyin; Han, Xiaoliang","year":2026,"journal":"American journal of translational research, 18(2), 1175-1185","doi":"10.62347/TGGD3922","pmid":"41868906","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16105","title":"Current research hotspots and difficulties of chronic prostatitis/chronic pelvic pain syndrome: neuroendocrine mechanism.","authors":"Shao, Bo; Wu, Kaixiu; Fan, Zhengkai; Gao, Xingwu; Wan, Shui; Xiao, Li; Zuo, Yanggen; Pi, Jinbo; Sun, Pingping","year":2026,"journal":"Annals of medicine, 58(1), 2616886","doi":"10.1080/07853890.2026.2616886","pmid":"41555741","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16106","title":"Dental Adhesive Peptides Nanonets as Multifunctional Therapy for Caries.","authors":"Shao, Liang; Song, Jiaqi; Wang, Ziyi; Shan, Xiaoyu; Zou, Wei; Meng, Caiting; Zhang, Yan; Zhu, Bin; Yang, Lulu; Yu, Xianyi; Zou, Jingjing; Li, Yunxuan; Su, Dan; Li, Guanying","year":2026,"journal":"Advanced healthcare materials, e03597","doi":"10.1002/adhm.202503597","pmid":"41560337","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16107","title":"SGLT2 inhibitors, GLP-1 RAs, and DPP4 inhibitors and the risk of hypomagnesemia in type 2 diabetes: A target trial emulation.","authors":"Shao, Shih-Chieh; Tsai, Daniel Hsiang-Te; Chuang, Albert Tzu-Ming; Liu, Kuan-Hung; Lai, Edward Chia-Cheng","year":2026,"journal":"PLoS medicine, 23(3), e1004968","doi":"10.1371/journal.pmed.1004968","pmid":"41790761","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16108","title":"Comparative evaluation of human ß defensin-2 in GCF and microbial flora in subgingival plaque among patients treated with conventional orthodontic braces and aligners: a prospective clinical study.","authors":"Sharma, Aditi; Kumar, Mukesh; Yadav, Ekta; Kumar, Sumit; Goyal, Manish; Rastogi, Sonal","year":2026,"journal":"Dental press journal of orthodontics, 30(6), e252541","doi":"10.1590/2177-6709.30.6.e252541.oar","pmid":"41615183","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16109","title":"Neuroprotective Role of Synthetic Peptide DP1 in Reducing Inflammation-Associated Brain Damage and Cognitive Impairments.","authors":"Sharma, Sheetal; Rai, Prachi; Maan, Mayank; Joshi, Shubhi; Barman, Panchali; Sharma, Satvika; Saini, Avneet","year":2026,"journal":"Chemistry & biodiversity, 23(2), e01139","doi":"10.1002/cbdv.202501139","pmid":"41386549","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16110","title":"Pre-digestion of soybeans, fermentation with fructophilic lactic acid bacteria, and in silico analyses to uncover psychobiotic potential.","authors":"Shazad, Amir; Tlais, Ali Zein Alabiden; Trossolo, Elisabetta; Casagrande Bacchiocchi, Sara; Filannino, Pasquale; Pinto, Daniela; Gobbetti, Marco; Di Cagno, Raffaella","year":2026,"journal":"Food research international (Ottawa, Ont.), 223(Pt 1), 117904","doi":"10.1016/j.foodres.2025.117904","pmid":"41352809","tags":[],"studyType":"in-vitro","evidenceStrength":"early","keyFinding":"Fermenting pre-digested soybeans with fructophilic lactic acid bacteria (FLAB) — specifically Apilactobacillus kunkeei and Fructobacillus fructosus — produced elevated levels of bioactive peptides, GABA, and beneficial phenolic compounds. The fermentation boosted low-molecular-weight peptides and generated novel peptide sequences beyond what digestion alone produced. Computer modeling predicted that several of these released peptides and phenolics could cross the blood-brain barrier and target neurotransmitter receptors, suggesting potential psychobiotic (brain-health) applications.","whyItMatters":"This study explores a novel way to create brain-active peptides and metabolites from soybeans using specialized bacteria found in bee-associated environments. It represents the convergence of food fermentation science, peptide research, and the gut-brain axis — suggesting that fermented soy products could be engineered to deliver neuroactive peptides with potential mental health benefits.","specificNumbers":"6 FLAB strains screened · 4 strains showed GI tolerance · GABA increased (PL34_DS) · Novel peptide sequences generated · Blood-brain barrier permeability predicted in silico","methodology":"Simulated gastrointestinal pre-digestion of soybeans, followed by fermentation with screened FLAB strains. Metabolite profiling measured amino acids, peptides, phenolics, short-chain fatty acids, and antinutritional factors. Computational (in silico) analysis predicted gastrointestinal absorption, blood-brain barrier permeability, and neurotransmitter receptor targeting of released compounds.","limitations":"Entirely in vitro and in silico — no animal or human studies to confirm that the predicted neuroactive effects actually occur. Computational predictions of blood-brain barrier permeability require experimental validation. The psychobiotic claims are speculative at this stage. FLAB strains are not commonly used in food production."},{"rthcId":"RPEP-16111","title":"Comparing Cardiovascular Outcomes of GLP-1 Receptor Agonists Versus Metabolic Bariatric Surgery: A Systematic Review and Meta-Analysis.","authors":"Shekouh, Dorsa; Behboodi, Mehrdad; Varmazyar, Matin; Khodadadiyan, Alireza; Jochin, Parnia; Bazrafshan Drissi, Hamed","year":2026,"journal":"Obesity surgery","doi":"10.1007/s11695-026-08500-z","pmid":"41644868","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16112","title":"Synergistic immune protection of exosomal T-cell epitope vaccine and antibody-inducing vaccine against SARS-CoV-2 in highly humanized mice.","authors":"Shen, Anran; Zhu, Suyue; Li, Min; Zhao, Yu; Wu, Yandan; Zhang, Yue; Zhang, Jiejie; Han, Xuelian; Wang, Yuan; Zhao, Guangyu; Lv, Linli; Yin, Qi; Tang, Taotao","year":2026,"journal":"Frontiers in immunology, 17, 1729444","doi":"10.3389/fimmu.2026.1729444","pmid":"41710875","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16113","title":"Designer Solid Self-Emulsifying Nanovaccines Enable Dual Modulation of Dendritic Cells and T Cells for Potent Antitumor Immunity.","authors":"Shen, Xueying; Fan, Shiqi; He, Jia; Luo, Lanqing; Li, Junyao; Wu, Chengcheng; Yang, Kairu; Xia, Xiaojun; Kuai, Rui","year":2026,"journal":"Advanced science (Weinheim, Baden-Wurttemberg, Germany), 13(5), e12139","doi":"10.1002/advs.202512139","pmid":"41199675","tags":[],"studyType":"animal-study","evidenceStrength":"preliminary","keyFinding":"A ~20 nm solid self-emulsifying (SSE) nanovaccine platform that co-delivers peptide antigens with a CpG oligonucleotide adjuvant generated T-cell responses 40-fold higher than conventional emulsified vaccines and achieved complete tumor regression at low doses in mice.\n\nThe mechanism is dual: ApoE (apolipoprotein E) adsorbed onto the nanoparticles enhanced lymph node targeting and dendritic cell uptake, while the nanoparticles were also directly internalized by T cells, promoting lipid raft formation that sensitized them to activation. This simultaneous engagement of both dendritic cells and T cells represents a previously unknown dual mechanism for nanovaccine-mediated immune activation.","whyItMatters":"Peptide cancer vaccines have been disappointing in clinical trials — they're safe but rarely generate strong enough immune responses to shrink tumors. A 40-fold improvement in T-cell response with complete tumor regression is a dramatic leap that could change the equation for peptide vaccine immunotherapy. The discovery that nanoparticles can directly activate T cells (not just dendritic cells) reveals a new design principle for future cancer vaccines.","specificNumbers":"~20 nm nanoparticle size · 40-fold higher T-cell response vs. conventional emulsified vaccines · Complete tumor regression at low doses · ApoE-mediated lymph node targeting · CpG adjuvant co-delivery","methodology":"Researchers designed solid self-emulsifying nanoparticles that encapsulate peptide antigens and CpG adjuvant. They characterized ApoE adsorption and lymph node targeting, measured dendritic cell internalization and T-cell activation, assessed lipid raft formation in T cells, and tested anti-tumor efficacy in C57BL/6 mouse tumor models.","limitations":"This is a mouse study, and tumor models in mice often respond better to immunotherapy than human cancers, which have more complex immune evasion mechanisms. The abstract doesn't specify which tumor model was used, how long regressions lasted, or whether they tested against established vs. newly implanted tumors. The 40-fold improvement is compared to conventional emulsified vaccines, not to other nanoparticle platforms."},{"rthcId":"RPEP-16114","title":"The promoting roles of GLP1R and GIPR in stemness maintenance and multiple lineage-specific differentiation of PDLSCs.","authors":"Shen, Yifen; Zhang, Mengjie; Yang, Tao; Wu, Yuxiang; Qiu, Yinfeng; Zhang, Le; Li, Fei; Chen, Minjie; Chen, Qili; Wei, Wenbin; Li, Hua; Shen, Yihang","year":2026,"journal":"Cellular & molecular biology letters, 31(1), 22","doi":"10.1186/s11658-026-00867-2","pmid":"41673566","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"This comprehensive study revealed distinct but complementary roles for GLP-1R and GIPR in periodontal stem cells:\n\n- GIPR agonism promoted PDLSC proliferation via the MAPK/ERK pathway\n- GLP-1R agonism enhanced multilineage differentiation capacity\n- GLP-1R knockdown upregulated IFIT1/2/3 proteins, which were shown to inhibit translation of differentiation-related mRNAs by interacting with translation initiation factor eIF3C\n- In vivo: single and dual receptor agonists improved periodontal regeneration in both wild-type and GLP-1R/GIPR double-knockout periodontitis mice\n- Clinical survey: 74 periodontitis patients taking GLP-1R or dual agonists showed significantly better periodontal staging and grading than non-users, with dose-duration relationship","whyItMatters":"Periodontitis (severe gum disease) affects nearly half of adults over 30 and is a leading cause of tooth loss. Current treatments are limited to cleaning procedures and surgery. If GLP-1 drugs — already prescribed to millions for diabetes and obesity — also improve periodontal health, it would represent a remarkable bonus benefit with immediate clinical relevance. The mechanistic depth of this study provides a strong biological foundation for this unexpected connection.","specificNumbers":"","methodology":"Multi-level investigation: (1) In vitro: PDLSCs exposed to stressors (e-cigarette extract, oral stressors) and analyzed for GLP-1R/GIPR expression; receptor knockdown/overexpression and agonist treatment assessed proliferation and differentiation. (2) Multi-omics: RNA-seq, ChIP-seq, and RIP-seq mapped downstream pathways. (3) In vivo: CRISPR-Cas9 mCherry-labeled PDLSCs transplanted into wild-type and double-knockout periodontitis mice, treated with receptor agonists, assessed by histology and lineage tracing. (4) Clinical survey: 150 periodontitis patients, 74 on GLP-1R or dual agonists for >1 month.","limitations":"The clinical survey (74 treated patients) is observational, not a randomized trial, and cannot prove causation. Confounding factors (e.g., weight loss itself improving systemic inflammation and periodontal health) were not fully controlled. The mouse periodontitis model may not fully replicate human disease. The in vitro stressor models are simplified. Specific drug doses and treatment durations varied among surveyed patients."},{"rthcId":"RPEP-16115","title":"Short- and long-acting GLP-1 receptor agonists decrease female sexual behaviors in experienced rodents.","authors":"Shevchouk, Olesya; Edvardsson, Christian E; Ericson, Mia; Blid Sköldheden, Sebastian; Zhang, Qian; Dreher Nabinger, Debora; Snoeren, Eelke Ms; Westberg, Lars; Jerlhag, Elisabet","year":2026,"journal":"Behavioural brain research, 504, 116085","doi":"10.1016/j.bbr.2026.116085","pmid":"41653988","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In female rats, the short-acting GLP-1R agonist exendin-4 reduced time spent with males, number of mounts, intromissions, ejaculations, darts, hops, and lordosis intensity. In female mice, the long-acting GLP-1R agonists liraglutide and dulaglutide reduced time spent with male mice and, consequently, lowered mounting and intromission duration.\n\nNeurochemically, the effects in mice potentially involved increased noradrenaline levels in the nucleus tractus solitarii (NTS) and altered glutamate, glutamine, and taurine levels in the lateral septum. Dulaglutide also decreased social novelty-seeking in the three-chamber test, while long-acting agonists increased sociability and novel object exploration time. Effects were both species-dependent and agonist-specific.","whyItMatters":"Millions of women take GLP-1 receptor agonists for diabetes and obesity, yet the effects of these drugs on sexual function in females have been largely ignored. This is the first study to systematically examine how these drugs affect female sexual and social behavior. Given the growing use of semaglutide and similar drugs, understanding their potential impact on sexual function is critical for informed prescribing and patient counseling.","specificNumbers":"","methodology":"Sexually experienced female rats and mice received either short-acting (exendin-4) or long-acting (liraglutide, dulaglutide) GLP-1 receptor agonists. Sexual behavior was assessed in paired encounters with males, measuring specific behavioral patterns. Social behavior was tested using the three-chamber social interaction test. Brain neurotransmitter levels were measured in the nucleus tractus solitarii and lateral septum.","limitations":"This is an animal study, and sexual behavior in rodents may not directly predict sexual function changes in humans. The specific drug doses and their equivalence to human therapeutic doses were not detailed in the abstract. The study only examined female animals, and effects may differ in males. The observed neurotransmitter changes are correlational and do not prove causation. Chronic dosing effects and reversibility were not assessed."},{"rthcId":"RPEP-16116","title":"A machine learning model for optimizing treatment of patients with poorly controlled type 2 diabetes.","authors":"Shi, Juan; Liu, Cong; Hu, Jiahang; Dai, Yuancheng; Peng, Ying; Xu, Fengmei; Shi, Haonan; Li, Yunsong; Li, Jun; Zhou, Zunhai; Wen, Chunfang; Huang, Shan; Shu, Yi; Ye, Xiaolin; Wang, Aifang; Zhao, Hongxia; Feng, Ping; Wu, Shengli; Wang, Dandan; Liu, Ping; Shi, Yi; Yang, Shuhui; Tu, Weiwei; Chen, Lei; Yu, Chaoli; Ning, Guang; Wang, Yufan; Zhao, Zhiyun; Zhang, Yifei; Wang, Weiqing","year":2026,"journal":"Communications medicine","doi":"10.1038/s43856-026-01442-8","pmid":"41703087","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16117","title":"Cardiac and renal sympathetic nerve activation in early-stage HFpEF: insights from 131I-MIBG imaging study.","authors":"Shi, Meijing; Yang, Zhiqiang; Yin, Pei; Zhao, Huayi; Li, Lizhuo; Zhen, Yuzhi; Zhao, Qingzhen; Liu, Chao","year":2026,"journal":"The international journal of cardiovascular imaging, 42(2), 283-292","doi":"10.1007/s10554-025-03586-5","pmid":"41385054","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16118","title":"Changes in interictal cerebral blood flow observed in migraine patients who respond to anti-calcitonin gene-related peptide therapy.","authors":"Shimoda, Masami; Hoshikawa, Kaori; Oda, Shinri; Imai, Masaaki; Aoki, Rie; Shinohara, Chiaki","year":2026,"journal":"Scientific reports, 16(1), 4699","doi":"10.1038/s41598-025-34910-7","pmid":"41495384","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16119","title":"Gepants for headache prevention in children and adolescents: A multicenter chart review study.","authors":"Shin, Lauren; Mentz, Olivia; Gelfand, Amy A; de Prado, Blanca Marquez; Shapiro, Hannah; Oh, Ann; Onifade, Ogo-Oluwa; Saunders, Jessica; Raj, Nichelle; Szperka, Christina L","year":2026,"journal":"Headache, 66(1), 239-248","doi":"10.1111/head.15087","pmid":"41235617","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 71 pediatric patients (55 on rimegepant, 26 on atogepant, 10 on both), 58% (32/55) of rimegepant users and 43% (11/26) of atogepant users experienced at least some benefit for headache prevention. This is notable because these were treatment-resistant patients who had already failed a median of 6-7 prior preventive medications.\n\nSide effects were infrequent and mild: only 4 of 55 rimegepant patients and 7 of 26 atogepant patients reported any side effects, with no serious adverse events. An exploratory analysis found that patients with longer headache histories were more likely to benefit (OR 1.41, 95% CI: 1.07-1.85, p=0.014), while those with more severe functional limitations were less likely to respond (OR 0.18, 95% CI: 0.05-0.58, p=0.004).","whyItMatters":"Migraine is one of the most disabling conditions in children and teens, yet very few preventive treatments have been studied or approved for this age group. Gepants represent a new class of peptide-targeting drugs that have proven effective in adults, and this real-world evidence provides the first multicenter look at how they perform in youth — filling a critical gap while randomized trials are still underway.","specificNumbers":"","methodology":"This was a multicenter retrospective chart review conducted at three major pediatric centers: Children's Hospital of Philadelphia, Cincinnati Children's Hospital, and UCSF Benioff Children's Hospital. Researchers reviewed records of all patients under 18 who were prescribed rimegepant or atogepant for headache prevention. Clinical data before and after treatment were collected using REDCap, and descriptive statistics summarized the findings.","limitations":"This was a retrospective chart review, not a randomized controlled trial, so there was no placebo comparison group and results may be influenced by selection bias and the placebo effect. The sample size was relatively small (71 patients), data collection at one site was a convenience sample, and the study was not designed to compare the two medications head-to-head. Follow-up periods and outcome measures were not standardized across sites."},{"rthcId":"RPEP-16120","title":"Patients' Experiences of Obstructive Sleep Apnea and Tirzepatide Treatment: An Exit Interview Study.","authors":"Shinde, Shraddha; Kanu, Chisom; Varnado, Oralee J; Bednarik, Jo; Dennehy, Ellen B; Dias-Barbosa, Carla; Taylor, Natalie","year":2026,"journal":"The patient","doi":"10.1007/s40271-026-00808-3","pmid":"41793578","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16121","title":"Association between semaglutide use and thyroid eye disease-related outcomes in autoimmune thyroiditis with type II diabetes.","authors":"Shlomov, Tehila; Nitzan, Itay; Pollack, Rena; Zloto, Ofira; Gur, Zvi","year":2026,"journal":"Canadian journal of ophthalmology. Journal canadien d'ophtalmologie","doi":"10.1016/j.jcjo.2026.01.010","pmid":"41620207","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16122","title":"Comparative Safety of GLP-1 Receptor Agonists Across Gastrointestinal, Renal and Pancreatic Systems.","authors":"Shokr, Hala; Mekkawy, Mohamed; Hindi, Ali","year":2026,"journal":"Pharmaceuticals (Basel, Switzerland), 19(1)","doi":"10.3390/ph19010136","pmid":"41599734","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16123","title":"Comparative efficacy of tirzepatide and glucagon-like peptide-1 receptor agonists on cardiovascular outcomes in patients with type 2 diabetes: a systematic review and network meta-analysis.","authors":"Shokravi, Arveen; Seth, Jayant; Mancini, G B John","year":2026,"journal":"Cardiovascular diabetology","doi":"10.1186/s12933-026-03113-3","pmid":"41761267","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In class-level analysis across 11 trials, tirzepatide vs. placebo significantly reduced: MACE (HR 0.79, 95% CI 0.69-0.91), cardiovascular mortality (HR 0.77, 95% CI 0.66-0.90), all-cause mortality (HR 0.74, 95% CI 0.65-0.83), non-fatal MI (HR 0.77, 95% CI 0.61-0.97), and non-fatal stroke (HR 0.79, 95% CI 0.64-0.97). In agent-level analysis, tirzepatide reduced MACE vs. placebo (HR 0.81) and vs. lixisenatide (HR 0.79), and showed comparable efficacy to other individual GLP-1RAs. Subgroup and sensitivity analyses were consistent.","whyItMatters":"With millions of patients choosing between GLP-1 agonists and tirzepatide, knowing whether tirzepatide provides similar cardiovascular protection is critical. This is the first network meta-analysis to formally position tirzepatide's cardiovascular outcomes against the full range of GLP-1 receptor agonists, confirming that the dual GIP/GLP-1 mechanism provides at least comparable heart protection — removing a key uncertainty that limited tirzepatide's positioning for cardiovascular risk reduction.","specificNumbers":"","methodology":"Systematic review and frequentist network meta-analysis of randomized controlled trials enrolling adults with type 2 diabetes and established atherosclerotic cardiovascular disease or high cardiovascular risk. Searches identified 11 eligible trials (10 GLP-1RA + SURPASS-CVOT for tirzepatide). Both class-level and agent-level analyses were conducted. Primary outcomes included MACE, cardiovascular mortality, all-cause mortality, non-fatal MI, and non-fatal stroke. Subgroup analyses for established CVD populations and leave-one-out sensitivity analyses were performed.","limitations":"Only one tirzepatide trial (SURPASS-CVOT) was available, limiting the precision of tirzepatide-specific estimates. Network meta-analysis relies on indirect comparisons with inherent uncertainty. Formal statistical comparison between tirzepatide and the GLP-1RA class could not be performed within the NMA framework. Individual trials had different designs, populations, and follow-up durations. Point estimates numerically favoring tirzepatide should be interpreted cautiously without direct head-to-head data."},{"rthcId":"RPEP-16124","title":"Association of parthenolide and salicin as a preventive treatment on a migraine model induced by dural inflammatory soup application.","authors":"Shrivastava, Remi; Ginisty, Aurelie; Da Silva Borges, Gisela; Descheemaeker, Amelie; Dallel, Radhouane; Monconduit, Lenaic","year":2026,"journal":"Pain, 167(2), 297-307","doi":"10.1097/j.pain.0000000000003789","pmid":"41512309","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16125","title":"GLP-1 Receptor Agonists and Cardiovascular Outcomes in Adults With Diabetes and Peripheral Artery Disease: An Updated Systematic Review and Meta-Analysis.","authors":"Shuja, Syed Hasan; Shuja, Muhammad Hamza; Shaukat, Ayesha; Hannat, Ramish; Ahmed, Ilsa; Adam, Siad; Abdelkhalek, Ahmed; Changez, Mah I Kan; Ullah, Irfan; Ahmed, Raheel; Cortese, Bernardo","year":2026,"journal":"The American journal of cardiology, 258, 268-275","doi":"10.1016/j.amjcard.2025.09.039","pmid":"41022246","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16126","title":"Improved health-related quality of life with tirzepatide versus semaglutide in adults with obesity or overweight from the SURMOUNT-5 trial.","authors":"Shukla, Alpana P; Dunn, Julia P; Gomez Valderas, Elisa; Fraseur Brumm, Julia; Karanikas, Chrisanthi A; Hunter Gibble, Theresa","year":2026,"journal":"Diabetes, obesity & metabolism, 28(1), 452-462","doi":"10.1111/dom.70215","pmid":"41187971","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"At Week 72, both tirzepatide and semaglutide improved Physical Component Summary scores from baseline. Tirzepatide showed significantly greater improvement in General Health domain scores compared to semaglutide (5.45 vs. 4.20; p = 0.003). All SF-36v2 domain scores improved with both treatments (p ≤ 0.008).\n\nIn the subgroup with limited baseline physical function, tirzepatide outperformed semaglutide in Physical Component Summary, Physical Functioning, and General Health scores (p ≤ 0.025). Greater body weight reductions were associated with more improvement in Physical Functioning, Role-Physical, Bodily Pain, General Health, and Vitality scores across both treatments when pooled. Mental Component Summary scores did not differ significantly between treatments.","whyItMatters":"This is the first head-to-head comparison of quality of life outcomes between tirzepatide and semaglutide — the two leading peptide-based obesity treatments. Beyond weight loss numbers, quality of life is what matters most to patients. Finding that tirzepatide provides an edge in general health perception, particularly for patients with physical limitations, helps clinicians and patients make more informed treatment decisions.","specificNumbers":"","methodology":"This is a prespecified analysis of health-related quality of life data from the SURMOUNT-5 randomized controlled trial. On-treatment data from participants receiving at least one dose of tirzepatide or semaglutide at maximum tolerated dose were analyzed at Week 72. Outcomes included SF-36v2 norm-based scores (Physical and Mental Component Summaries and individual domains), Patient Health Questionnaire-9, and Patient Global Impression of Status for Physical Activity. Post hoc analyses examined outcomes by baseline physical function and by body weight reduction thresholds.","limitations":"The quality of life analysis uses on-treatment data, which may overestimate benefits by excluding participants who discontinued due to side effects. The general health domain difference, while statistically significant, is modest in absolute terms. Mental health scores did not differ between treatments, and some subgroup analyses were post hoc. The study enrolled adults without type 2 diabetes, so results may not generalize to the diabetic obesity population."},{"rthcId":"RPEP-16127","title":"Tumor-specific antibody cocktail treatment suppresses colorectal tumor growth in mice.","authors":"Shukla, Girja S; Pero, Stephanie C; Sun, Yujing; Mei, Linda; Barrantes-Reynolds, Ramiro; Fournier, Matthew R; Ackerman, Margaret E; Krag, David N","year":2026,"journal":"Cancer immunology, immunotherapy : CII, 75(3)","doi":"10.1007/s00262-026-04337-8","pmid":"41739229","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16128","title":"Nonhormonal Pharmacological Interventions in Adolescent Polycystic Ovary Syndrome (PCOS): A Systematic Review.","authors":"Sibal, Rhea; Keogh, Morgan; Latthe, Pallavi; Idkowiak, Jan","year":2026,"journal":"Journal of pediatric and adolescent gynecology","doi":"10.1016/j.jpag.2026.01.001","pmid":"41506442","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"This first-ever systematic review of nonhormonal treatments for adolescent PCOS found that metformin alone modestly reduced BMI (1–2 kg/m²), improved insulin resistance (25% HOMA-IR reduction), and restored menstrual cycles in up to 91% of participants. The SPIOMET combination improved ovulatory function, halved hirsutism scores, reduced visceral and liver fat, and normalized inflammatory markers with benefits lasting up to one year post-treatment. Critically, no clinical trials of GLP-1 receptor agonist monotherapy in adolescents with PCOS were identified, representing a major evidence gap.","whyItMatters":"Despite growing adult use of GLP-1 receptor agonist peptide drugs for metabolic conditions, there is zero adolescent-specific data for their use in PCOS. This review highlights a critical gap in peptide therapeutics research for a condition affecting millions of young women, while showing that existing nonhormonal options like SPIOMET may offer multi-domain benefits.","specificNumbers":"19 studies · 744 adolescents · BMI reduction 1–2 kg/m² · 25% HOMA-IR improvement · 91% menstrual restoration · Ferriman-Gallwey scores halved with SPIOMET · 0 GLP-1RA trials in adolescents","methodology":"Systematic review searching Medline, EMBASE, Cochrane Library, and CINAHL from 1990 to June 2025. Included RCTs, cohort, and case-control studies enrolling PCOS patients aged 12–19 years. Two independent reviewers screened, extracted data, and assessed quality. Outcomes included clinical signs, metabolic indices, hormonal markers, and quality of life.","limitations":"Most included studies were small and observational rather than large RCTs. The evidence base is limited to 744 total adolescents across 19 studies. No GLP-1RA trials were available for analysis. Heterogeneity in outcome measures across studies limits comparison."},{"rthcId":"RPEP-16129","title":"Effect of glucagon-like peptide-1 agonists on deep inferior epigastric perforator flap breast reconstruction outcomes in obese patients: A study of 5618 patients.","authors":"Sidhu, Angad S; Chopra, Avani A; Ahmed, Shahnur; Corpuz, George S; Towfighi, Parhom N; Danforth, Rachel M; Lester, Mary E; Hassanein, Aladdin H","year":2026,"journal":"Journal of plastic, reconstructive & aesthetic surgery : JPRAS, 113, 194-197","doi":"10.1016/j.bjps.2025.11.048","pmid":"41308379","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16130","title":"Nutritional and lifestyle supportive care recommendations for management of obesity with GLP-1 - based therapies: An expert consensus statement using a modified Delphi approach.","authors":"Sievenpiper, J L; Ard, J; Blüher, M; Chen, W; Dixon, J B; Fitch, A; Gigliotti, L; Khunti, K; Lecube, A; Lean, M E J; Mittendorfer, B; Pfeiffer, A F H; Ryan, D H; Vilsbøll, T; Van Gaal, L F","year":2026,"journal":"Obesity pillars, 17, 100228","doi":"10.1016/j.obpill.2025.100228","pmid":"41502845","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The expert panel produced 52 consensus statements covering nutritional and lifestyle management for patients on GLP-1-based therapies (GBTs). Key areas addressed include: nutritional factors related to obesity and body composition, physical activity recommendations, and management of common gastrointestinal symptoms (nausea, vomiting, diarrhea, constipation).\n\nThe recommendations are organized by treatment phase: before starting a GBT, during active weight loss, during weight maintenance, and upon GBT discontinuation. The panel emphasized that GI side effects, obesity-associated nutritional insufficiencies, and poor long-term adherence may limit the health benefits of these drugs without proper supportive care.","whyItMatters":"Millions of people are now taking GLP-1 drugs for weight loss, but most clinical trial data focuses on drug efficacy rather than day-to-day supportive care. This consensus fills a critical practice gap by providing healthcare professionals with structured guidance on how to help patients optimize their results and manage side effects throughout their treatment journey.","specificNumbers":"","methodology":"An initial scoping review searched PubMed, Embase, Web of Science, Cochrane, and Medline for publications from January 2021 through June 2025. An international multidisciplinary panel then used a modified Delphi process — a structured method where experts independently rate statements through multiple rounds until consensus is reached — to develop clinical practice recommendations.","limitations":"The consensus statements were primarily derived from indirect evidence — existing guidelines for bariatric medicine nutrition therapy and clinical experience — rather than direct evidence from studies specifically conducted in GLP-1 therapy patients. The authors explicitly note that direct evidence is urgently needed. Consensus-based recommendations may reflect expert opinion rather than proven best practices."},{"rthcId":"RPEP-16131","title":"Beyond Weight Loss: Holistic Impacts of a Digital Weight Management Programme Integrating Tirzepatide.","authors":"Sikorska, Lena M; Liu, Vivian N; Johnson, Hans; Chaudry, Earim; Reisel, Daniel; Clift, Ashley K; Huang, David R","year":2026,"journal":"Cureus, 18(2), e102817","doi":"10.7759/cureus.102817","pmid":"41788104","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16132","title":"Design and Synthesis of Peptide-Polyester Conjugates for Cell-Mediated Scaffold Degradation.","authors":"Sinad, Korina Vida G; Hunt, Natasha K; Singh, Srujan; Seims, Kelly B; Wu, Yingjie; Pashuck, E Thomas; Grayson, Warren L; Chow, Lesley W","year":2026,"journal":"Advanced healthcare materials, e04885","doi":"10.1002/adhm.202504885","pmid":"41721596","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Key results from the peptide-PCL conjugate system:\n\n- A 'Fast' peptide sequence was identified via functional mass spectrometry as selectively cleavable by multiple cell types\n- Peptide incorporation did not impair cell adhesion (tested with RGDS-PCL)\n- Collagenase degradation (21 days): Fast-PCL released 25.77% ± 3.70% Cy3 label vs 11.31% ± 1.01% for scrambled control; mass loss 22.1% vs 18.9%\n- hMSC-mediated degradation: Fast-PCL released 26.68% ± 2.17% vs 18.97% ± 1.24% for scrambled control\n- Degradation was sequence-dependent (not just bulk hydrolysis), confirming cell-directed proteolytic resorption\n- Cy3 real-time labeling enabled quantitative tracking of degradation","whyItMatters":"A major challenge in tissue engineering is matching scaffold degradation to tissue growth. If the scaffold breaks down too slowly, it blocks new tissue formation; too fast, and it loses structural support. By incorporating cell-cleavable peptides, this approach lets the body's own cells control the degradation rate — the scaffold breaks down exactly where and when cells are building new tissue. This is particularly important for craniofacial bone repair, where precise structural remodeling is critical.","specificNumbers":"","methodology":"A functional mass spectrometry approach screened peptide sequences for protease cleavability across multiple cell types. The 'Fast' peptide and a scrambled control were conjugated into the PCL polymer backbone and solvent-cast with RGDS-PCL into disks. Cy3 fluorescent labeling enabled real-time degradation quantification. Degradation was tested with purified collagenase and with human mesenchymal stromal cells (hMSCs) over 21 days. Cell adhesion was verified on composite scaffolds.","limitations":"The study was conducted in vitro using cell cultures and purified enzymes, not in living bone. The 21-day timeframe may not reflect the months-long process of actual bone regeneration. Only one fast-degrading peptide sequence was tested in scaffolds. The mechanical properties of peptide-containing PCL compared to standard PCL were not fully characterized. In vivo bone regeneration studies are needed."},{"rthcId":"RPEP-16133","title":"Obesity-Driven Hypertension: Exploring the Mechanisms and Modern Treatment Strategies.","authors":"Sindhwani, Ninaad; Moudgil, Pyush; Thukral, Jatin; Shah, Riya Kaushal; Kaur, Harbir; Kumar, Rajat; Thukral, Nikhil; Raval, Maharshi; Agrawal, Siddharth Pravin; Frishman, William H; Aronow, Wilbert S","year":2026,"journal":"Cardiology in review","doi":"10.1097/CRD.0000000000001193","pmid":"41622529","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16134","title":"Hemolytik 2: An Updated Database of Hemolytic Peptides and Proteins.","authors":"Singh, Ayushi; Sa, Kavin Raj; Rathore, Anand Singh; Raghava, Gajendra P S","year":2026,"journal":"Chemical research in toxicology, 39(2), 208-215","doi":"10.1021/acs.chemrestox.5c00322","pmid":"41525503","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16135","title":"Oral Peptide Nano-Formulations for Breast Cancer: An Enhancer-Centric, Regulatory-Ready Path to Clinical Translation.","authors":"Singh, Dilpreet; Singh, Bishal; Chawla, Pooja A; Chawla, Viney","year":2026,"journal":"Journal of peptide science : an official publication of the European Peptide Society, 32(4), e70091","doi":"10.1002/psc.70091","pmid":"41732004","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16136","title":"Neurogenic Inflammation and Immune Dysregulation in Psoriasis: Mechanistic Pathways and Emerging Interventions.","authors":"Singh, Hemraj; Taliyan, Rajeev","year":2026,"journal":"The American journal of pathology, 196(3), 633-643","doi":"10.1016/j.ajpath.2025.11.005","pmid":"41391748","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16137","title":"Next-generation biocontrol: The role of antimicrobial peptides in sustainable agriculture.","authors":"Singh, Jyoti P; Tilgam, Jyotsana; R K, Bhavyasree; Kumar, Adarsh; Thapa, Shobit; Vishwakarma, Ritu; Pandey, Rashmi; Kumar, Jaygendra; Kumar, Mahesh; Kashyap, Abhijeet S; Srivastava, Alok K","year":2026,"journal":"Microbial pathogenesis, 211, 108252","doi":"10.1016/j.micpath.2025.108252","pmid":"41422870","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16138","title":"Thioredoxin-mimetic peptide attenuates epilepsy progression and neurocognitive deficits.","authors":"Singh, Prince Kumar; Maurya, Shweta; Saadi, Aseel; Sandouka, Sereen; Zhang, Taige; Kadosh, Orya; Sheeni, Yara; Martin, Valeria; Atlas, Daphne; Shekh-Ahmad, Tawfeeq","year":2026,"journal":"Redox biology, 90, 104021","doi":"10.1016/j.redox.2026.104021","pmid":"41544351","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In vitro, CB3 pretreatment (50-100 μM) reduced oxidative activity and pro-inflammatory cytokines (IL-6, IL-1β, TNF-α) while increasing anti-inflammatory IL-10 in an epileptiform activity model.\n\nIn vivo, early CB3 intervention (20 mg/kg/day, i.p.) after kainic acid-induced status epilepticus significantly delayed seizure onset, reduced seizure frequency and cumulative burden, and preserved hippocampal neuronal integrity. Treated mice showed improved locomotor activity, reduced anxiety, and better spatial working memory. In established chronic epilepsy, CB3 (20 mg/kg/day) produced sustained reduction in recurrent seizure activity and seizure burden with improvements in anxiety, though memory deficits remained unchanged.","whyItMatters":"Current anti-seizure medications are purely symptomatic — they suppress seizures but don't prevent epilepsy from developing or worsening. With 30-40% of patients being drug-resistant, there is an urgent need for disease-modifying therapies. CB3 appears to go beyond seizure suppression by targeting the underlying oxidative stress and inflammation that drive disease progression, while also protecting neurons.","specificNumbers":"","methodology":"The study used complementary in vitro and in vivo approaches. Cell culture models used low-Mg2+-induced epileptiform activity to test CB3's effects on oxidative stress and inflammation. In vivo, kainic acid-induced status epilepticus in mice modeled temporal lobe epilepsy. CB3 was tested both as early intervention (started after initial seizures) and in established chronic epilepsy. Outcomes included seizure monitoring, hippocampal histology, and behavioral assessments (locomotion, anxiety, spatial memory).","limitations":"All experiments were conducted in mice; translation to human epilepsy patients is uncertain. Memory and learning deficits were not improved by CB3 in the chronic epilepsy model, suggesting some established damage may be irreversible. The study used intraperitoneal injection, and oral bioavailability is not addressed. Long-term safety data and optimal dosing for human use would need extensive further study."},{"rthcId":"RPEP-16139","title":"Engineering Marker-Free Lettuce Chloroplast Genome to Express Functional Glucagon-Like Peptide-1 Receptor Agonists Exenatide and Lixisenatide.","authors":"Singh, Rahul; Daniell, Henry","year":2026,"journal":"Plant biotechnology journal","doi":"10.1111/pbi.70554","pmid":"41578882","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16140","title":"Emerging Multi-Target Therapies for Type 2 Diabetes: Bridging Drug Innovation and Precision Delivery.","authors":"Singhal, Priya; Mazumder, Rupa; Rani, Anjna; Debnath, Abhijit","year":2026,"journal":"Current topics in medicinal chemistry","doi":"10.2174/0115680266429073251122045133","pmid":"41540544","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies several key therapeutic targets and delivery strategies for T2DM:\n\n- GLP-1 receptor agonists: enhance insulin secretion, reduce appetite, and provide cardiovascular benefits\n- SGLT2 inhibitors: block renal glucose reabsorption\n- AMPK activators: improve cellular energy metabolism\n- PPAR-γ modulators: enhance insulin sensitivity\n- Glucose absorption inhibitors: reduce dietary glucose uptake\n\nMulti-targeted therapy combining these approaches has demonstrated potential for improved glycemic control, reduced long-term complications, and better safety profiles compared to monotherapy. Precision drug delivery using receptor-targeted carriers can enhance bioavailability and reduce dosing frequency.","whyItMatters":"Type 2 diabetes is a multi-factorial disease that single drugs often cannot adequately control. The shift toward multi-target therapy reflects a growing understanding that addressing several metabolic pathways simultaneously — including the GLP-1 peptide pathway — produces better outcomes. Combined with precision delivery that targets specific cells, this approach could transform diabetes care from one-size-fits-all to personalized therapy.","specificNumbers":"","methodology":"This is a narrative review of recent literature on emerging therapeutic targets and drug delivery strategies for type 2 diabetes, covering both pharmacological targets and advanced delivery systems.","limitations":"This is a narrative review without systematic methodology or meta-analysis. The abstract does not cite specific clinical trial data or quantitative comparisons between multi-target and monotherapy approaches. Many of the drug delivery strategies discussed may still be in early preclinical stages. The review covers a very broad topic, which may limit the depth of coverage for any individual therapeutic target."},{"rthcId":"RPEP-16141","title":"Effects of commercial genetic selection on gene expression in the developing neuroendocrine system of broilers.","authors":"Sinpru, Panpradub; Diehl, Kristen; Ellestad, Laura E; Porter, Tom E","year":2026,"journal":"Poultry science, 105(2), 106331","doi":"10.1016/j.psj.2025.106331","pmid":"41475176","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16142","title":"The Effect of GLP-1 Receptor Agonists on Autophagy: Insights Gathered from Research Evaluating Neurodegenerative Disorders With These Agents.","authors":"Sioufi, Maria-Christina; Heroiu, Isabela; Wong, Sabrina; Le, Gia Han; Dri, Christine E; Zheng, Yang Jing; Rhee, Taeho Greg; Lo, Heidi Ka Ying; Guillen-Burgos, Hernan F; Teopiz, Kayla M; McIntyre, Roger S","year":2026,"journal":"Acta neuropsychiatrica, 1-36","doi":"10.1017/neu.2026.10060","pmid":"41684077","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 14 included studies, GLP-1RAs (liraglutide, semaglutide, exendin-4) consistently modulated autophagy-specific markers in Alzheimer's and Parkinson's disease models: increased beclin-1, LC3-II/LC3-I ratio, ATG7, ATG3, and LAMP1, while normalizing p62 levels. These changes indicate enhanced autophagosome formation and clearance of cellular debris.\n\nIn addition to autophagy modulation, GLP-1RAs promoted neurogenesis, enhanced neuroplasticity, and reduced neuroinflammation — suggesting autophagy may be one of several interconnected mechanisms mediating the broad neuroprotective effects of these peptide drugs.","whyItMatters":"Alzheimer's and Parkinson's currently have no disease-modifying treatments that effectively halt progression. If GLP-1 receptor agonists — already widely used and well-characterized drugs — can enhance the brain's natural protein cleanup system, they could be repurposed for neurodegenerative diseases. This would dramatically shorten the path to clinical application compared to developing entirely new drugs.","specificNumbers":"","methodology":"Systematic review following established guidelines, searching PubMed, Web of Science, and OVID (Medline, Embase, APA PsycInfo) from inception to June 2025. Two independent reviewers screened 142 identified studies using predefined criteria, including 14 that evaluated GLP-1RA effects on autophagy markers in cell and animal models of AD and PD. Quality assessment was conducted.","limitations":"All 14 included studies were preclinical (cell and animal models), with no human clinical data on autophagy modulation by GLP-1RAs in neurodegeneration. Autophagy markers were assessed differently across studies, making direct comparisons challenging. The review was limited to AD and PD models and may not apply to other neurodegenerative conditions. Whether brain GLP-1R activation at clinically relevant doses produces sufficient autophagy enhancement in humans remains unknown."},{"rthcId":"RPEP-16143","title":"Effect of glucagon-like peptide-1 receptor agonists on histologic MASH: A meta-analysis of randomized controlled trials.","authors":"Siranart, Noppachai; Thompson, Christopher C; Jirapinyo, Pichamol","year":2026,"journal":"Hepatology communications, 10(2)","doi":"10.1097/HC9.0000000000000871","pmid":"41543478","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"At 18 months, GLP-1RA-treated patients were significantly more likely to achieve MASH resolution without worsening fibrosis compared to placebo (OR: 4.16, 95% CI: 2.33-7.42, p<0.001). In a subgroup analysis excluding cirrhotic patients, GLP-1RAs also showed significant fibrosis regression of at least one stage (OR: 2.02, 95% CI: 1.56-2.62, p=0.01).\n\nGLP-1RAs significantly improved all liver histologic features examined: balloon degeneration (a marker of cell injury), lobular inflammation, and steatosis (fat accumulation). The overall nonalcoholic fatty liver disease activity score improved significantly. Serious adverse event rates were comparable between GLP-1RA and placebo groups.","whyItMatters":"MASH is the most common chronic liver disease worldwide and a leading cause of liver transplantation, yet treatment options have been extremely limited until recently. The first drug specifically approved for MASH (resmetirom) only arrived in 2024. This meta-analysis provides the strongest evidence to date that GLP-1 receptor agonists — already widely prescribed for diabetes and obesity — can resolve the underlying liver disease and even reverse early scarring. This could fundamentally change how clinicians manage the large overlap population of patients with diabetes, obesity, and fatty liver disease.","specificNumbers":"","methodology":"This was a meta-analysis of six randomized controlled trials identified through a literature search up to May 2025. All trials evaluated FDA-approved GLP-1 receptor agonists in patients with biopsy-confirmed MASH. The primary outcomes were MASH resolution without fibrosis worsening and fibrosis improvement without MASH worsening at 12-18 months. The analysis included 1,555 patients total — 1,082 on GLP-1RAs and 473 on placebo. Subgroup analysis was performed excluding studies that included cirrhotic patients.","limitations":"The meta-analysis included only six trials with 1,555 patients, which is moderate but not large for a meta-analysis. Individual GLP-1RA drugs were pooled together, which may mask differences in efficacy between specific medications. The fibrosis benefit was significant only in the subgroup excluding cirrhotic patients, suggesting GLP-1RAs may not help those with advanced disease. Follow-up was limited to 12-18 months — the long-term effects on liver outcomes like decompensation, hepatocellular carcinoma, and transplant need remain unknown."},{"rthcId":"RPEP-16144","title":"Current clinical application of incretin therapy for obesity management.","authors":"Skinner, Karlie; Clements, Jennifer N","year":2026,"journal":"Canadian journal of physiology and pharmacology, 104, 1-8","doi":"10.1139/cjpp-2025-0152","pmid":"41420876","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide and tirzepatide have demonstrated weight loss outcomes that have fundamentally shifted the obesity treatment paradigm. These incretin-based therapies work by modulating GLP-1 (and in tirzepatide's case, also GIP) receptor pathways, leading to decreased caloric intake through appetite suppression.\n\nThe review notes that benefits extend beyond weight loss to include metabolic improvements, though challenges remain around long-term efficacy (weight regain after discontinuation), tolerability (gastrointestinal side effects), and accessibility (cost and supply constraints). Future directions include combination therapies and novel molecules with dual or triple receptor activity targeting GLP-1, GIP, and glucagon receptors simultaneously.","whyItMatters":"Obesity affects over 1 billion people worldwide and drives cardiovascular disease, type 2 diabetes, and numerous other conditions. Until recently, pharmacological options for obesity were limited and modestly effective. The GLP-1 receptor agonist class has changed this dramatically, producing weight loss of 15-20% or more — approaching what was previously only achievable with bariatric surgery. This review helps clinicians navigate the practical aspects of prescribing these medications.","specificNumbers":"","methodology":"This is a narrative clinical review that synthesizes published clinical trial data and guidelines on the use of GLP-1 receptor agonists (liraglutide, semaglutide) and dual GLP-1/GIP receptor agonists (tirzepatide) for obesity management. It focuses on practical clinical application rather than basic science.","limitations":"As a narrative review, this article synthesizes existing evidence rather than presenting new data. The review acknowledges but may not fully quantify several key limitations of incretin therapy: weight regain after discontinuation, long-term safety beyond available trial durations, gastrointestinal tolerability, cost barriers ($1,000+ per month without insurance coverage in many settings), and supply chain constraints that have limited access. The review does not address potential concerns about muscle mass loss during rapid weight reduction."},{"rthcId":"RPEP-16145","title":"Challenges in the management of obesity.","authors":"Smith, Bradley L; May, Alexandria; Lalani, Falak; Hasham, Salman; Presnell, Allison A","year":2026,"journal":"Journal of clinical lipidology, 20(1S), 126-134","doi":"10.1016/j.jacl.2025.09.023","pmid":"41708210","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16146","title":"Fourier Transform Infrared Spectroscopic Characterization of Aortic Wall Remodeling by Stable Gastric Pentadecapeptide BPC 157 After Unilateral Adrenalectomy in Rats.","authors":"Smoday, Ivan Maria; Vukovic, Vlasta; Oroz, Katarina; Vranes, Hrvoje; Kalogjera, Luka; Gamulin, Ozren; Vlainic, Josipa; Milavic, Marija; Sikiric, Suncana; Nikolac Gabaj, Nora; Marijancevic, Domagoj; Koprivanac, Antun; Beketic Oreskovic, Lidija; Oreskovic, Ivana; Strbe, Sanja; Barisic, Ivan; Kordic, Mario; Tvrdeic, Ante; Seiwerth, Sven; Sikiric, Predrag; Boban Blagaic, Alenka; Skrtic, Anita","year":2026,"journal":"Pharmaceuticals (Basel, Switzerland), 19(1)","doi":"10.3390/ph19010191","pmid":"41599787","tags":[],"studyType":"animal","evidenceStrength":"preliminary","keyFinding":"Using FTIR spectroscopy to analyze rat aortic tissue after unilateral adrenalectomy, researchers found that a single oral dose of BPC 157 (10 ng/kg) produced clear, reproducible molecular changes in the aortic wall at all time points (15 minutes, 5 hours, and 24 hours post-surgery). The spectral changes were concentrated in protein-related bands (amide I and amide II, consistent with collagen/elastin) and lipid C-H stretching bands.\n\nThese molecular signatures suggest that BPC 157 promotes rapid extracellular matrix reinforcement and membrane preservation in the vascular wall — providing molecular-level evidence for the peptide's previously observed vascular protective effects.","whyItMatters":"BPC 157 is one of the most widely discussed peptides in the research community, but its mechanisms of action remain poorly understood. This study provides molecular-level spectroscopic evidence for how BPC 157 may protect blood vessels, showing structural changes consistent with strengthening of the vessel wall's collagen/elastin framework and preservation of cell membranes — observable within just 15 minutes of oral administration.","specificNumbers":"","methodology":"Rats underwent unilateral adrenalectomy and received either BPC 157 (10 ng/kg intragastrically) or control treatment immediately after surgery. Abdominal aortas were collected at 15 minutes, 5 hours, and 24 hours post-surgery. The tissue was analyzed using Fourier transform infrared (FTIR) spectroscopy, with data processed through principal component analysis (PCA), support vector machine discriminant analysis (SVMDA), and band-specific statistics to identify spectral differences.","limitations":"This is an animal study in rats with a very specific surgical model (unilateral adrenalectomy). FTIR spectroscopy reveals molecular structural changes but does not directly prove functional improvement. The study does not include long-term follow-up, and the clinical relevance of these spectral changes to human vascular health is unknown. BPC 157 research has been heavily concentrated among a small group of researchers."},{"rthcId":"RPEP-16147","title":"Tirzepatide in Adults With Type 1 Diabetes: A Phase 2 Randomized Placebo-Controlled Clinical Trial.","authors":"Snaith, Jennifer R; Frampton, Ruth; Samocha-Bonet, Dorit; Greenfield, Jerry R","year":2026,"journal":"Diabetes care, 49(1), 161-170","doi":"10.2337/dc25-2379","pmid":"41264593","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Over 12 weeks, tirzepatide produced a mean weight loss of 10.3 kg versus 0.7 kg with placebo (treatment difference: -8.7 kg, p<0.0001), representing 8.8% body weight reduction. Every participant (100%) on tirzepatide achieved at least 5% weight loss, and 45% achieved at least 10% loss, compared to 9% and 0% on placebo.\n\nTirzepatide also improved HbA1c by -0.4% versus placebo (p=0.05) and reduced total daily insulin dose by 24.2 units/day (35.1% reduction vs placebo, p=0.0002). No significant adverse events occurred in either group. Twenty-two of 24 participants completed the study.","whyItMatters":"Obesity affects a growing proportion of people with type 1 diabetes and increases cardiovascular risk, but no weight loss medications have been specifically studied or approved for this population. This first-ever RCT of tirzepatide in type 1 diabetes shows it can produce substantial weight loss and reduce insulin needs without safety concerns — potentially opening a new treatment avenue for millions of patients.","specificNumbers":"","methodology":"This was a 12-week, phase 2, double-blind, placebo-controlled trial in adults with type 1 diabetes and BMI >30 kg/m². Participants were randomized to weekly subcutaneous tirzepatide (2.5 mg for 4 weeks, then 5.0 mg for 8 weeks) or placebo. The primary endpoint was change in body weight at 12 weeks. Secondary endpoints included HbA1c, insulin dose, and safety.","limitations":"This was a small phase 2 trial with only 24 participants and 12-week duration. The tirzepatide dose was capped at 5 mg (lower than the 10-15 mg used in type 2 diabetes obesity studies), so the full potential may not have been captured. Longer-term safety, durability of weight loss, and effects at higher doses need evaluation. The study excluded participants with BMI under 30, so applicability to overweight (non-obese) type 1 diabetes patients is unknown."},{"rthcId":"RPEP-16148","title":"Sex-based differences in the enteroendocrine system and food intake regulation due to dietary protein replacement by Alphitobius Diaperinus in rats.","authors":"Soler, Oria; Lores, Mònica; Rodríguez-Gallego, Esther; Terra, Ximena; Beltrán-Debón, Raúl; Ribas-Agustí, Albert; Matas, Grau; Ardévol, Anna; Pinent, Montserrat","year":2026,"journal":"Food research international (Ottawa, Ont.), 229, 118423","doi":"10.1016/j.foodres.2026.118423","pmid":"41763763","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16149","title":"LL-37 antimicrobial peptide: Molecular characterisation and its role in oral health and disease-A narrative review.","authors":"Soman, Drisya; P, Jayanthi; Cm, Mahesh; Radhakrishnan, Rahul","year":2026,"journal":"Archives of oral biology, 183, 106516","doi":"10.1016/j.archoralbio.2026.106516","pmid":"41544412","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"LL-37 is expressed by gingival epithelium, salivary glands, and inflammatory cells in the oral cavity. Beyond direct antimicrobial killing, it modulates inflammatory responses, promotes wound healing, and influences cell proliferation and blood vessel formation. Altered LL-37 expression has been associated with periodontitis, dental caries, endodontic infections, and oral squamous cell carcinoma. The review positions LL-37 as both a potential diagnostic biomarker and therapeutic target in oral pathology.","whyItMatters":"Oral diseases including periodontitis and dental caries affect billions of people worldwide. Current treatments focus on mechanical removal of bacteria (brushing, scaling) and antibiotics. Understanding how the body's own antimicrobial peptide system works — and fails — in the mouth could lead to fundamentally different treatment approaches: boosting natural LL-37 production, using synthetic LL-37 analogs as therapeutics, or using LL-37 levels as early disease biomarkers.","specificNumbers":"","methodology":"Narrative review with comprehensive literature searches across PubMed, Scopus, and Google Scholar. Included in vitro, in vivo, and clinical studies evaluating LL-37 expression, mechanisms of action, and pathological implications in oral tissues.","limitations":"This is a narrative review without systematic methodology, so study selection may be subject to bias. The evidence linking LL-37 alterations to specific oral diseases is largely associative rather than causal. Most mechanistic studies are in vitro or in animal models. Clinical applications of LL-37 in dentistry remain theoretical — no LL-37-based oral therapies or diagnostic tests have been validated in clinical trials."},{"rthcId":"RPEP-16150","title":"Potential therapeutic role of GLP-1 receptor agonists in Idiopathic intracranial hypertension: a systematic review and meta-analysis.","authors":"Song, Jiahao; Fang, Kun; Zhang, Yunzhou; Zhang, Rujiang; Yin, Chengliang; Gao, Daiquan","year":2026,"journal":"Neurological research, 1-15","doi":"10.1080/01616412.2026.2640121","pmid":"41776834","tags":["glp-1"],"studyType":"meta-analysis","evidenceStrength":"strong","keyFinding":"A meta-analysis of 7 studies with 11,973 participants found that GLP-1 receptor agonists significantly reduced the incidence of refractory idiopathic intracranial hypertension (IIH), lowered the risk of papilledema by 60% (RR=0.40), and reduced visual disturbances and blindness risk by 49% (RR=0.51). GLP-1RAs also reduced headache incidence (RR=0.74) and monthly headache days (SMD=-0.77).\n\nHowever, objective visual parameters — visual acuity, visual field measurements, and retinal nerve fiber layer thickness — did not significantly improve. Interestingly, BMI changes were not significant either, suggesting the benefits may come through mechanisms other than weight loss alone.","whyItMatters":"Idiopathic intracranial hypertension causes debilitating headaches and can lead to permanent vision loss. Current treatments are limited. This meta-analysis provides the strongest evidence to date that GLP-1 drugs — already widely used for diabetes and weight loss — could be repurposed to treat this challenging neurological condition, potentially preventing blindness in affected patients.","specificNumbers":"7 studies · n=11,973 · RR=0.40 papilledema risk · RR=0.51 visual disturbances/blindness · RR=0.74 headache incidence · SMD=-0.77 monthly headache days","methodology":"Systematic review and meta-analysis following PRISMA guidelines. Researchers searched PubMed, Embase, Web of Science, Scopus, and the Cochrane Library through July 2025. Seven studies with 11,973 total participants were included. Random-effects models pooled relative risks (RRs) and standardized mean differences (SMDs) for IIH outcomes.","limitations":"Most included studies were likely observational rather than randomized controlled trials, which limits causal conclusions. The non-significant improvement in objective visual measurements (despite reduced papilledema and blindness risk) is puzzling and may reflect measurement timing or sensitivity issues. The non-significant BMI change raises questions about the mechanism of action in IIH."},{"rthcId":"RPEP-16151","title":"Generation and characterisation of a humanised GLP-1 receptor mouse model for translational drug development.","authors":"Sonne, Nina; Roque, Micaela; Zachariassen, Line Fisker; Porsgaard, Trine; Pors, Susanne E; Cavalera, Michele; Jones, Christopher; Osborn, Olivia; Thorbek, Ditte Dencker; Riis, Malene Lundgaard; Feigh, Michael; Quinn, Kevin; Gaidarov, Ibragim; Anthony, Todd; Hansen, Henrik H; Tozzi, Marco","year":2026,"journal":"EBioMedicine, 124, 106121","doi":"10.1016/j.ebiom.2026.106121","pmid":"41547115","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16152","title":"OSA screening before CGRP mAbs in chronic migraine.","authors":"Soomro, M I; Mirza, S A; Khalid, M S","year":2026,"journal":"Sleep & breathing = Schlaf & Atmung, 30(1), 24","doi":"10.1007/s11325-025-03563-1","pmid":"41591680","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16153","title":"Amyloid-beta (1-40) peptide is associated with systemic metabolic health.","authors":"Sopova, Kateryna; Delialis, Dimitrios; Aivalioti, Evmorfia; Georgiopoulos, Georgios; Athanasopoulos, Stravros; Zervas, Georgios; Konstantaki, Christina; Sachse, Marco; Sigl, Martin; Duerschmied, Daniel; Tual-Chalot, Simon; Stamatelopoulos, Kimon; Stellos, Konstantinos","year":2026,"journal":"European journal of clinical investigation, 56(1), e70171","doi":"10.1111/eci.70171","pmid":"41502294","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16154","title":"Pep5-Cpp, a Cyclin D2-Derived Antimicrobial.","authors":"Souto, Bianca Silva; Hasbahr, Vitória Stephani; da Silva, Bárbara Ribeiro Lourenço; de Mattos, Thais Lemos; de Oliveira, André Souza; Abe, Cecília Mari; Franzolin, Marcia Regina; da Silva Junior, Pedro Ismael; Rioli, Vanessa","year":2026,"journal":"Molecules (Basel, Switzerland), 31(4)","doi":"10.3390/molecules31040634","pmid":"41752412","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16155","title":"Network Meta-Analysis: Comparison of Pharmacological Therapies in Compensated Metabolic Dysfunction-Associated Steatohepatitis Cirrhosis for Fibrosis Regression and MASH Resolution.","authors":"Souza, Matheus; Al-Sharif, Lubna; Antunes, Vanio L J; Wong, Shi Yin; Huang, Daniel Q; Loomba, Rohit","year":2026,"journal":"Alimentary pharmacology & therapeutics","doi":"10.1111/apt.70565","pmid":"41645601","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 9 RCTs with 3,266 participants, efruxifermin was the only intervention significantly superior to placebo for fibrosis regression (≥1 stage improvement without MASH worsening), ranking highest (SUCRA 77.44), followed by cilofexor + firsocostat (SUCRA 72.38) and aldafermin (SUCRA 71.27).\n\nFor MASH resolution, three treatments were significantly superior to placebo: efruxifermin (SUCRA 81.38), semaglutide + cilofexor + firsocostat (SUCRA 74.07), and semaglutide alone (SUCRA 63.88).","whyItMatters":"MASH cirrhosis is rapidly becoming one of the most common causes of liver transplantation and liver-related death worldwide. Until recently, no drugs were approved for this condition. This analysis provides the first head-to-head ranking of emerging therapies, helping guide both clinical trial design and future treatment decisions as these drugs move toward approval.","specificNumbers":"","methodology":"Systematic review and network meta-analysis of randomized controlled trials from PubMed and Cochrane Library through May 2025. Included studies evaluated pharmacological treatments in biopsy-proven compensated MASH cirrhosis (F4c). SUCRA ranking analysis estimated the probability of each treatment being the most effective.","limitations":"Network meta-analyses rely on indirect comparisons between trials with different designs, populations, and durations. The number of included trials (9) is relatively small, limiting the precision of rankings. SUCRA rankings do not represent absolute efficacy differences. Safety profiles were not compared. The analysis included only compensated cirrhosis, so results may not apply to decompensated disease."},{"rthcId":"RPEP-16156","title":"Megalomyrmex milenae Transcriptome Reveals a Complex Venom Cocktail.","authors":"Sozanski, Kyle S; Coelho, Guilherme R; Ishihara, Marcela Akemi; Delgado, Alonso; Adams, Rachelle M M","year":2026,"journal":"Toxins, 18(1)","doi":"10.3390/toxins18010055","pmid":"41591201","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16157","title":"Outcome trajectories in hospitalized heart failure with preserved ejection fraction: a machine learning cluster analysis.","authors":"Spagnolin, Marco; Fazzini, Luca; Giaccherini, Cinzia; D'Elia, Emilia; Chiesa, Erika; Zucchi, Alberto; Gavazzi, Antonello; Senni, Michele; Gori, Mauro","year":2026,"journal":"European journal of heart failure","doi":"10.1093/ejhf/xuag037","pmid":"41740597","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16158","title":"Bridging Innovation and Practice in Type 2 Diabetes Mellitus: Novel Antidiabetic Therapies and the Expanding Role of Community Pharmacists.","authors":"Spanakis, Marios; Fournaraki, Agapi; Nimee, Frantzeska; Kontogiorgis, Christos; Symvoulakis, Emmanouil K","year":2026,"journal":"Pharmaceuticals (Basel, Switzerland), 19(2)","doi":"10.3390/ph19020271","pmid":"41754812","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16159","title":"Superior NET Targeting by Switch From Agonist to Antagonist-mediated Somatostatin Receptor Theranostics Allowing Successful (LM3-based) PRRT of Otherwise Precluded mNET: Intraindividual Proof-of-concept.","authors":"Speicher, Tilman; Burgard, Caroline; Rosar, Florian; Bastian, Moritz; Bartholomä, Mark; Maus, Stephan; Ezziddin, Samer","year":2026,"journal":"Clinical nuclear medicine, 51(1), e25-e26","doi":"10.1097/RLU.0000000000005936","pmid":"40296275","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Standard agonist-based imaging (68Ga-DOTATOC PET/CT) showed insufficient tumor uptake, precluding conventional PRRT. Switching to the antagonist-based tracer (68Ga-NODAGA-LM3 PET/CT) revealed markedly superior and treatment-sufficient uptake in the same patient.\n\nThis directly translated to successful therapy: 4 cycles of 177Lu-DOTA-LM3 PRRT produced a positive treatment response. The case demonstrates both diagnostic superiority of antagonist over agonist somatostatin receptor imaging and the feasibility of antagonist-mediated PRRT in patients who fail agonist-based approaches.","whyItMatters":"Approximately 20-30% of neuroendocrine tumor patients show insufficient uptake on standard agonist-based imaging, excluding them from PRRT — one of the most effective targeted therapies for these cancers. This case demonstrates that antagonist-based peptides can detect and treat tumors that agonist peptides miss, potentially expanding PRRT eligibility to a significant population of currently untreatable patients.","specificNumbers":"","methodology":"This is a single-patient proof-of-concept case report with intraindividual comparison. The same patient underwent sequential PET/CT imaging with both the agonist tracer (68Ga-DOTATOC) and the antagonist tracer (68Ga-NODAGA-LM3), enabling direct comparison of tumor uptake. Following successful antagonist imaging, the patient received 4 cycles of antagonist-based PRRT (177Lu-DOTA-LM3) and treatment response was assessed.","limitations":"This is a single case report — the lowest level of clinical evidence. The positive response is documented but specific imaging and response metrics are not detailed in the abstract. Long-term outcomes and durability of response are unknown. LM3-based PRRT is not yet widely available or approved, and larger studies are needed to establish safety and efficacy profiles compared to standard DOTATATE-based PRRT."},{"rthcId":"RPEP-16160","title":"Beyond diabetes and obesity: GLP-1 receptor agonists in disrupting the vicious cycle of metabolic dysfunction and neuroinflammation.","authors":"Spezani, Renata; Mandarim-de-Lacerda, Carlos A","year":2026,"journal":"Diabetes, obesity & metabolism, 28(3), 1622-1637","doi":"10.1111/dom.70400","pmid":"41417476","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16161","title":"Nutrition Strategies for Next-Generation Incretin Therapies: A Systematic Scoping Review of the Current Evidence.","authors":"Spreckley, Marie; Ruggiero, Cara F; Brown, Adrian","year":2026,"journal":"Obesity reviews : an official journal of the International Association for the Study of Obesity, e70079","doi":"10.1111/obr.70079","pmid":"41500509","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16162","title":"Non-diabetic Kidney Disease in Type 2 Diabetes: From Kidney Biopsy to Precision Medicine.","authors":"Sreedharan, Sreenath; M K, Mohandas; K B, Vismaya; Raju, Nikhil","year":2026,"journal":"Cureus, 18(1), e100716","doi":"10.7759/cureus.100716","pmid":"41646563","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"NDKD affects one-third to one-half of T2DM patients with kidney disease. IgA nephropathy dominates in Asian populations (25-43%), while membranous nephropathy (20-30%) and FSGS (18-25%) are more common in Western cohorts. Clinical predictors include absence of diabetic retinopathy (OR 0.15 for DKD), diabetes <5 years (OR 5.8 for NDKD), hematuria (OR 7.2), and rapid eGFR decline >5 mL/min/year (OR 4.3). For renoprotection: SGLT2 inhibitors show HR 0.61-0.72, GLP-1 RAs ~0.76, and MRAs ~0.82. AI-assisted histopathology achieves AUC 0.91 for diagnosis.","whyItMatters":"Misdiagnosing non-diabetic kidney disease as diabetic nephropathy leads to missed treatment opportunities — these patients need specific immunosuppressive therapies. At the same time, renoprotective peptide-based therapies like GLP-1 receptor agonists benefit kidney function regardless of the underlying cause. This review provides a framework for integrating biopsy-guided precision medicine with universal renoprotective strategies, including the growing role of GLP-1RAs in kidney protection.","specificNumbers":"","methodology":"Narrative review of PubMed, EMBASE, and Scopus (January 2020-December 2024), including systematic reviews, meta-analyses, RCTs, cohort studies, and clinical guidelines addressing NDKD in diabetes.","limitations":"This is a narrative review without systematic methodology or meta-analysis. The prevalence estimates for NDKD vary widely across studies and populations. The GLP-1RA hazard ratio cited (~0.76) represents pooled evidence that may not apply equally to all NDKD subtypes. Kidney biopsy, while the gold standard, carries procedural risks and is not appropriate for all patients. AI-assisted diagnostic tools are promising but not yet widely available."},{"rthcId":"RPEP-16163","title":"Glucagon-Like Peptide-1 Receptor Agonists in Individuals With Severe Mental Illness: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.","authors":"Srisurapanont, Manit; Suttajit, Sirijit; Likhitsathian, Surinporn; Suradom, Chawisa; Maneeton, Benchalak","year":2026,"journal":"International journal of psychiatry in medicine, 912174261422822","doi":"10.1177/00912174261422822","pmid":"41618880","tags":[],"studyType":"meta-analysis","evidenceStrength":"moderate","keyFinding":"Across 10 randomized controlled trials with 665 participants, GLP-1 receptor agonists significantly reduced body weight by 6.17 kg (95% CI: -9.10 to -3.25) and HbA1c by 0.31% (95% CI: -0.40 to -0.22) compared to placebo in individuals with severe mental illness (schizophrenia, schizophrenia-spectrum disorders, bipolar disorder).\n\nCritically, dropout rates were no different between GLP-1 RA and placebo groups — both all-cause (RR 0.98) and adverse-effect dropouts (RR 0.99) — indicating acceptable tolerability in this vulnerable population.","whyItMatters":"People with severe mental illness have dramatically higher rates of obesity and diabetes, largely due to antipsychotic medications that cause significant weight gain. They also die 15–20 years earlier than the general population, primarily from cardiovascular disease. GLP-1 drugs could be transformative for this underserved population — but their safety alongside psychiatric medications needed specific evidence, which this meta-analysis provides.","specificNumbers":"10 RCTs · n=665 · Weight loss: -6.17 kg · HbA1c: -0.31% · Dropout RR 0.98 (no difference) · Exenatide, liraglutide, semaglutide studied · I²=91.8% for weight","methodology":"Systematic review and meta-analysis of randomized controlled trials found in PubMed, Embase, Cochrane Library, Google Scholar, and ClinicalTrials.gov (searched December 2025). Included 10 RCTs of exenatide, liraglutide, or semaglutide in participants with schizophrenia, schizophrenia-spectrum disorders, or bipolar disorder with cardiometabolic risk. Random-effects models estimated mean differences and risk ratios.","limitations":"High heterogeneity for weight outcomes (I²=91.8%) suggests significant variation across trials. Small total sample size (665 participants) limits precision. Evidence certainty was graded as low for efficacy/tolerability and moderate for acceptability. The trials used different GLP-1 RAs at different doses, limiting direct comparisons. Tirzepatide was not included."},{"rthcId":"RPEP-16164","title":"Pleural and Pericardial Effusions Associated with Semaglutide: A Case Report.","authors":"Stark, Maggie; Valentini, Nicholas","year":2026,"journal":"Clinical practice and cases in emergency medicine, 10(1), 93-96","doi":"10.5811/cpcem.48864","pmid":"41666880","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16165","title":"Truncated Equinin B Variants Reveal the Sequence Determinants of Antimicrobial Selectivity.","authors":"Staropoli, Mariele; Schwaiger, Theresa; Tuzlak, Jasmina; Biba, Renata; Petrowitsch, Lukas; Fessler, Johannes; Roje, Marin; Cammarata, Matteo; Malanović, Nermina; Jakas, Andreja","year":2026,"journal":"Marine drugs, 24(1)","doi":"10.3390/md24010046","pmid":"41590743","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16166","title":"Proteomic effects of short-term liraglutide vs. placebo in a blinded crossover RCT: Implications for efficacy, safety, and comparison with semaglutide.","authors":"Stefanakis, Konstantinos; Gutierrez de Piñeres, Valeria; Veeragandham, Preethi; Mantzoros, Christos S","year":2026,"journal":"Metabolism: clinical and experimental, 177, 156493","doi":"10.1016/j.metabol.2026.156493","pmid":"41513169","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16167","title":"Effects of GLP-1 receptor agonists on vascular dementia: a systematic review and meta-analysis.","authors":"Stefanou, Maria-Ioanna; Tentolouris, Anastasios; Panagiotopoulos, Evangelos; Theodorou, Aikaterini; Mengel, Annerose; Athanasaki, Athanasia; Lambadiari, Vaia; Peppa, Melpomeni; Papadopoulou, Marianna; Paraskevas, Georgios P; Giannopoulos, Sotirios; Siasos, Gerasimos; Sharma, Vijay K; Ziemann, Ulf; Tsivgoulis, Georgios","year":2026,"journal":"Journal of diabetes and its complications, 40(3), 109271","doi":"10.1016/j.jdiacomp.2026.109271","pmid":"41619622","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16168","title":"Efficacy and safety of glucagon-like peptide-1 receptor agonists in Parkinson's disease: a systematic review and meta-analysis of randomized placebo-controlled clinical trials.","authors":"Stefanou, Maria-Ioanna; Panagiotopoulos, Evangelos; Tentolouris, Anastasios; Theodorou, Aikaterini; Papagiannopoulou, Georgia; Athanasaki, Athanasia; Tsalouchidou, Panagiota-Eleni; Peppa, Melpomeni; Lambadiari, Vaia; Konitsiotis, Spiridon; Mengel, Annerose; Paraskevas, Georgios P; Tentolouris, Nikolaos; Tsivgoulis, Georgios","year":2026,"journal":"Therapeutic advances in neurological disorders, 19, 17562864251408269","doi":"10.1177/17562864251408269","pmid":"41631108","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16169","title":"Natural and Synthetic Peptides as Alternatives to Antibiotics in Intestinal Infections-A Review.","authors":"Stepanyan, Lala; Israyelyan, Monika; Gori, Alessandro; Tsaturyan, Avetis; Saribekyan, Zhaklina; Hovsepyan, Kristina; Sargsyan, Tatevik; Pastore, Raffaele; De Luca, Antonio; Roviello, Giovanni N","year":2026,"journal":"Antibiotics (Basel, Switzerland), 15(1)","doi":"10.3390/antibiotics15010068","pmid":"41594104","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Natural antimicrobial peptides (AMPs) including defensins, cathelicidins, histatins, lactoferricin, protamines, RegIII, and hepcidin demonstrated significant antimicrobial and immunomodulatory effects against major gastrointestinal pathogens including E. coli, Klebsiella pneumoniae, Salmonella, and Shigella. Beyond directly killing bacteria, these peptides modulate host-microbiota interactions, preserve gut barrier integrity, and limit inflammation.\n\nSynthetic peptide analogs such as WR12, D-IK8, MSI-78, and IMX942 showed improved stability, reduced toxicity to human cells, and synergistic effects when combined with conventional antibiotics, suggesting potential use as standalone treatments or combination therapies.","whyItMatters":"Antibiotic resistance is one of the most pressing global health threats, and gastrointestinal infections are among the most common infectious diseases. Antimicrobial peptides offer a fundamentally different approach to fighting infections — they have broad-spectrum activity, develop resistance slowly, and can boost the immune system while preserving the beneficial gut microbiome. This makes them promising alternatives to conventional antibiotics.","specificNumbers":"7+ natural AMP classes reviewed · 4+ synthetic analogs evaluated · Activity against E. coli, K. pneumoniae, Salmonella, Shigella · Low resistance development propensity","methodology":"This is a literature review of recent peer-reviewed studies on antimicrobial peptides, focusing on their mechanisms of action, antimicrobial spectrum against gastrointestinal pathogens, and interactions with standard antibiotics.","limitations":"As a review, this paper does not present new experimental data. Most AMP evidence comes from in vitro studies, and the authors note that more clinical trials are needed to translate promising lab results into reliable patient outcomes. Formulation challenges including stability and delivery also remain to be solved."},{"rthcId":"RPEP-16170","title":"Selective Serine Substitutions of Antimicrobial Peptides Reveal Different Mechanistic Actions Toward Gram-Negative Bacteria.","authors":"Stephens, Anna; Ge, Tianhao; Ding, Ke; Hollowell, Peter; Clifton, Luke; Hall, Stephen; Li, Peixun; Webster, John R P; Gong, Haoning; Lu, Jian Ren","year":2026,"journal":"ACS applied materials & interfaces, 18(7), 10860-10873","doi":"10.1021/acsami.5c22475","pmid":"41697071","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Selective substitution of lysine with serine in the designed AMP G(IIKK)3I-NH2 altered both the charge distribution and amphiphilicity of the peptide, resulting in different structural disruptions to the inner and outer membranes of gram-negative bacteria. Serine-rich AMPs showed improved antimicrobial activity linked to intramembrane aggregation — the peptides clustered within the bacterial membrane, causing more effective disruption. Neutron reflection experiments and molecular dynamics simulations confirmed these distinct mechanistic pathways, demonstrating that rational amino acid substitutions can fine-tune how antimicrobial peptides attack bacterial membranes.","whyItMatters":"Antimicrobial resistance kills over a million people annually and is projected to worsen. Unlike traditional antibiotics, antimicrobial peptides kill bacteria through rapid membrane disruption, making it extremely difficult for bacteria to evolve resistance. Understanding precisely how amino acid changes affect the killing mechanism allows researchers to rationally design more effective peptide-based antibiotics.","specificNumbers":"","methodology":"The researchers used a multi-technique approach combining antimicrobial activity assays against gram-negative bacteria (E. coli and P. aeruginosa), neutron reflection to visualize peptide-membrane interactions at the molecular level, and molecular dynamics simulations to model how the peptides aggregate within and disrupt bacterial membrane structures.","limitations":"The study examines peptide-membrane interactions using model membranes and in vitro bacterial assays, which may not fully represent the complexity of in vivo infections. Toxicity to human cells is not assessed in the abstract. The work focuses on gram-negative bacteria; effectiveness against gram-positive species is not addressed. The path from optimized peptide sequence to clinical therapeutic remains long and uncertain."},{"rthcId":"RPEP-16171","title":"Elastin-derived peptide hydrogels for sustained dermal delivery of tetrapeptide-21.","authors":"Stephenson, Hannah; Lim, Amabella; Dupuy, Rachel; Brun, Serena; Armstrong, Amy; Okunola, Nobunaga; Li, Nicola Ann; Hilkens, Catharien M U; Novakovic, Katarina; Hills, Samantha; Ng, Keng Wooi; Al Musaimi, Othman","year":2026,"journal":"International journal of pharmaceutics, 689, 126490","doi":"10.1016/j.ijpharm.2025.126490","pmid":"41421628","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16172","title":"Perceptions of GLP-1 RA Use for Children With Obesity Among Caregivers With Food Insecurity: A Qualitative Study.","authors":"Stephenson, Kathryn M; Schwartz, Naomi R M; Person, Hannibal; Blondet, Niviann; Benitez-Cortez, Maria E; Nuding, Mason; Kraft, Stephanie A; Suskind, David L","year":2026,"journal":"JAMA network open, 9(1), e2552825","doi":"10.1001/jamanetworkopen.2025.52825","pmid":"41499114","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16173","title":"Euglycemic Ketoacidosis Following the Use of Counterfeit Semaglutide for Weight Loss.","authors":"Sterckx, Mira; De Keyser, Ludo","year":2026,"journal":"Cureus, 18(1), e102627","doi":"10.7759/cureus.102627","pmid":"41773123","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16174","title":"Glucagon-Like Peptide-1 Receptor Agonists as a Non-surgical Alternative to Bariatric Surgery for Weight Loss: A Review.","authors":"Steven, Chuh; Skylynn, Thangwaritorn; Bardya, Haghighat; Megha, Bhalla; Helen, Vuong; Lee, Duo; Entabi, Fateh; Pemminati, Sudhakar","year":2026,"journal":"Cureus, 18(1), e100704","doi":"10.7759/cureus.100704","pmid":"41635371","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16175","title":"Case Series of Nizon-Isidor Syndrome by Heterozygous Variants in MED12L With Further Evidence of Mitotic Instability in One Case With Diploid-Triploid Mosaicism.","authors":"Stewart, Russell; Ezell, Kimberly M; Bell, Deanna S; Corner, Brian; McMinn, Ashley; Cogan, Joy D; Hamid, Rizwan; Rives, Lynette; Phillips, John A; Paddu, Nina; Srivastava, Gitanjali; Marom, Ronit; Ladha, Farah A; Soler-Alfonso, Claudia; Franciskovich, Rachel; Koziura, Mary; Pruthi, Sumit; Richard, Gabriele; Sheedy, Christina B; Cassini, Thomas","year":2026,"journal":"American journal of medical genetics. Part A, 200(1), 205-214","doi":"10.1002/ajmg.a.64233","pmid":"40838347","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16176","title":"Broad-Spectrum Activity of Peptide-Linked Amikacin Conjugates in Synergy with Polymyxin B against Extensively Drug-Resistant and Pandrug-Resistant Bacteria.","authors":"Story, Sandra; Sharma, Anindra; Maiti, Krishnagopal; Arya, Dev P","year":2026,"journal":"ACS infectious diseases, 12(1), 298-313","doi":"10.1021/acsinfecdis.5c00798","pmid":"41460792","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Peptide-linked amikacin conjugates showed powerful synergy with polymyxin B against extensively drug-resistant and pandrug-resistant Klebsiella pneumoniae. Of 31 resistant strains tested, 77% showed synergy when peptide-amikacin conjugates containing tryptophan and cysteine were combined with polymyxin B, including strains carrying multiple resistance enzymes (AMEs and RMTases). The peptide-linked compounds maintained similar mammalian cell toxicity as unmodified amikacin but were dramatically more synergistic with polymyxin B against resistant bacteria.","whyItMatters":"Drug-resistant Klebsiella pneumoniae is at the top of the WHO's critical priority pathogen list, and existing antibiotics are rapidly losing effectiveness. By linking amino acid peptides to the antibiotic amikacin, researchers created a new class of conjugates that restore antibiotic activity against bacteria that are resistant to virtually everything. This peptide-modification strategy could be a lifeline against the growing threat of untreatable infections.","specificNumbers":"31 K. pneumoniae strains · 77% showed synergy · peptides with tryptophan and cysteine most effective · active against AME and RMTase carriers · pandrug-resistant strains included","methodology":"Researchers chemically synthesized a library of peptide-linked amikacin derivatives, attaching amino acids with different properties (positively charged, sulfur-containing, or aromatic side chains). These conjugates were tested alone and in combination with polymyxin B against 31 Klebsiella pneumoniae strains with various resistance mechanisms. Synergy was assessed using standard antimicrobial susceptibility testing, and mammalian cell toxicity was evaluated.","limitations":"This is an in vitro study; the peptide-amikacin conjugates have not been tested in animal models or humans. Pharmacokinetic properties (absorption, distribution, metabolism) of the conjugates are unknown. The study focused on Klebsiella pneumoniae — activity against other critical priority pathogens needs testing. The combination still requires polymyxin B, which has its own toxicity concerns."},{"rthcId":"RPEP-16177","title":"Aspiration Risk During Endoscopic Procedures While on GLP-1 Agonist Therapy.","authors":"Stryelkina, Maryana; Molina, Robert; Janice, Thomas; Ancha, Anupama; Bejcek, Justin; Ian, Fladie; Mullarkey, Michael; Johnson, Christopher","year":2026,"journal":"Digestive diseases and sciences, 71(1), 211-220","doi":"10.1007/s10620-025-09307-1","pmid":"40783459","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16178","title":"Glucagon-Like Peptide-1 Receptor Agonist Use Is Associated With Decreased Incidence of Carpal Tunnel Syndrome in Patients With Type 2 Diabetes: A Propensity-Matched Analysis.","authors":"Stump, Kyle; Centeno, Dianly; Talsania, Alec; Morar, Henry; Wiekrykas, Bradley","year":2026,"journal":"Hand (New York, N.Y.), 15589447261422503","doi":"10.1177/15589447261422503","pmid":"41719026","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16179","title":"Preoperative Use of Glucagon-Like Peptide-1 Receptor Agonists Is Not Protective Against Pseudoarthrosis Following Small Joint Hand Arthrodesis: A Propensity-Matched Analysis.","authors":"Stump, Kyle; Morar, Henry; Talsania, Alec; Centeno, Dianly; Wiekrykas, Bradley","year":2026,"journal":"Hand (New York, N.Y.), 15589447261415646","doi":"10.1177/15589447261415646","pmid":"41620384","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16180","title":"ROS-responsive nanoliposomes loaded with anti-oomycetes medium-chain fatty acids for shuttling delivery in plant disease control.","authors":"Su, Chenyu; Xu, Kangwen; Xing, Xuexia; Liu, Yuan; Yang, Yahui; Zhao, Donglin; Zhang, Chengsheng","year":2026,"journal":"Journal of nanobiotechnology, 24(1)","doi":"10.1186/s12951-025-03979-7","pmid":"41629930","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16181","title":"Functional and Morphological Outcomes of Duration-Dependent Electrical Stimulation in Silicone Conduit-Mediated Peripheral Nerve Repair in Rats.","authors":"Su, Ching-Feng; Lu, Ming-Hsuan; Lee, Joanna Pi-Jung; Chen, Chung-Chia; Chen, Yung-Hsiang; Chen, Yueh-Sheng","year":2026,"journal":"Bioengineering (Basel, Switzerland), 13(2)","doi":"10.3390/bioengineering13020218","pmid":"41749757","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16182","title":"Bioinspired Engineering of Streamlined Skeletal Interoception: Neural Bioprinted Piezoelectric Scaffolds for Neuro-Vascularized Bone Regeneration.","authors":"Su, Yingze; Wang, Haomin; Liu, Weixi; Chen, Kangming; Min, Yiyang; Zhu, Jinbo; Li, Xueyang; Su, Anning; Yang, Hao; Yang, Lei; Ji, Yun; Zhang, Yuxin; Zheng, Jisi; Yang, Chi; He, Chuanglong; Li, Tao; Chen, Shuo; Wu, Tao; Chen, Xiaodong","year":2026,"journal":"Advanced science (Weinheim, Baden-Wurttemberg, Germany), e24181","doi":"10.1002/advs.202524181","pmid":"41691467","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Researchers engineered a self-contained sensor-effector circuit by bioprinting dorsal root ganglion (DRG) neurons within piezoelectric poly(L-lactide) (PLLA) scaffolds. Upon ultrasound stimulation, the piezoelectric material generated electrical signals that triggered calcium influx in the DRG neurons, enhancing secretion and expression of calcitonin gene-related peptide (CGRP). The released CGRP promoted both osteogenesis and angiogenesis in vitro, and accelerated neuro-vascularized bone regeneration in a rat femoral condyle defect model — demonstrating a bioinspired platform that autonomously links mechanical sensing to peptide-driven bone repair.","whyItMatters":"Current bone scaffolds are passive structures that don't replicate the body's natural nerve-driven healing signals. By creating a scaffold that actively produces CGRP peptide in response to ultrasound, this approach bridges the gap between bioengineering and the body's own bone repair mechanisms — potentially leading to faster, more complete bone healing with proper nerve and blood vessel integration.","specificNumbers":"","methodology":"The researchers used neural bioprinting to embed dorsal root ganglion neurons within piezoelectric PLLA scaffolds. They applied ultrasound stimulation to trigger mechanoelectrical coupling, measuring calcium influx and CGRP secretion. In vitro experiments assessed osteogenesis and angiogenesis. In vivo testing used a rat femoral condyle defect model to evaluate bone regeneration, vascularization, and nerve integration.","limitations":"This is an animal study using a rat femoral condyle defect model, which does not fully replicate human bone healing. The approach requires external ultrasound stimulation, adding complexity to clinical application. Long-term durability and safety of the bioprinted neural scaffolds in larger animals or humans remain untested. CGRP also plays roles in pain signaling, which could have unintended effects."},{"rthcId":"RPEP-16183","title":"Application of the protease-resistant antimicrobial peptide R7I, composed of natural amino acids, as a functional food ingredient for modulating intestinal health.","authors":"Su, Yunzhe; Sun, Taotao; Yang, Qin; Liu, Yi; Zhang, Jing; Shan, Anshan","year":2026,"journal":"Food research international (Ottawa, Ont.), 225, 118073","doi":"10.1016/j.foodres.2025.118073","pmid":"41508493","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16184","title":"Gut Microbiota-Derived Trimethylamine N-Oxide and NT-proBNP in Heart Failure: A Critical Review of Diagnostic and Prognostic Value.","authors":"Suchecka, Natalia Anna; Popławska, Patrycja; Obrycka, Patrycja; Frątczak, Agnieszka; Tokarz, Ewa; Soczyńska, Julia; Woźniak, Sławomir","year":2026,"journal":"Biomedicines, 14(2)","doi":"10.3390/biomedicines14020287","pmid":"41751186","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16185","title":"Weight Loss Patterns and Clinical Outcomes of GLP1 Receptor Agonists in Breast Cancer Survivors.","authors":"Sukumar, Jasmine S; Raghavendra, Akshara S; Pasyar, Sarah; Bassett, Roland L; Tripathy, Debu; Barcenas, Carlos H; Basen-Engquist, Karen M; Arun, Banu K","year":2026,"journal":"Cancer research communications, 6(3), 447-455","doi":"10.1158/2767-9764.CRC-25-0554","pmid":"41677473","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16186","title":"Reestimation of Medicare Spending for Semaglutide After Most Favored Nation and Medicare Drug Price Negotiation Announcements.","authors":"Sullivan, Sean D; Dayer, Victoria; Kasle, Adam; Nourhussein, Iman; Hansen, Ryan N","year":2026,"journal":"Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research","doi":"10.1016/j.jval.2026.01.016","pmid":"41651376","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16187","title":"Structure-Activity Relationship and Biosafety of Linear Pentapeptide Analogs Derived from Battacin for Antimicrobial Development.","authors":"Sun, Haixin; Zhang, Yujie; Gi, Guoqing; Yao, Chen","year":2026,"journal":"Antibiotics (Basel, Switzerland), 15(2)","doi":"10.3390/antibiotics15020208","pmid":"41750505","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16188","title":"IL-6 blockade at the fracture site accelerates bone healing via inflammatory modulation of sensory nerve CGRP signaling.","authors":"Sun, Lipeng; Kuang, Shouxiang; Wang, Chang; Li, Yang; Wang, Guodong; Sun, Jianmin; Zhou, Fengge; Zhang, Chenggui","year":2026,"journal":"International immunopharmacology, 173, 116258","doi":"10.1016/j.intimp.2026.116258","pmid":"41581244","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16189","title":"LL37-induced mitochondrial stress activates the mtDNA/cGAS/STING pathway to promote mast cell-mediated rosacea inflammation.","authors":"Sun, Rui; Fan, Huiping; Ma, Qingsong; Li, Xiaojin; Liu, Jiayun; Xu, Chen; Liu, Chengqi; Zhang, Dong; Ma, Weiyuan","year":2026,"journal":"Free radical biology & medicine, 244, 422-434","doi":"10.1016/j.freeradbiomed.2025.12.026","pmid":"41421415","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16190","title":"Tirzepatide reduces intracellular lipid content by promoting the browning of white fat via the cAMP signaling pathway.","authors":"Sun, Yaqin; Xia, Yin; Ge, Weixing; Li, Qian","year":2026,"journal":"European journal of pharmacology, 1014, 178523","doi":"10.1016/j.ejphar.2026.178523","pmid":"41506434","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Tirzepatide significantly reduced body weight and white adipose tissue mass in obese mice, with marked reduction in fat cell size (adipocyte hypertrophy). RNA sequencing revealed coordinated upregulation of thermogenesis and lipid metabolism genes. The drug increased expression of browning markers PGC-1α and UCP1, indicating white fat was converting to a calorie-burning brown-like state.\n\nIn cultured 3T3-L1 adipocytes, tirzepatide activated the PGC-1α/UCP1 axis in a cAMP-dependent manner and reduced lipid droplet accumulation. When the adenylyl cyclase inhibitor SQ22536 was added, these browning effects were significantly attenuated, confirming cAMP signaling as the critical mediator.","whyItMatters":"Tirzepatide is already one of the most effective weight-loss and diabetes drugs available, but exactly how it reduces body fat has not been fully understood. This study reveals a direct, fat-cell-specific mechanism: tirzepatide doesn't just reduce appetite — it actively reprograms fat tissue to burn calories. Understanding this pathway opens doors for developing even more targeted obesity treatments and helps explain why tirzepatide produces such dramatic weight loss in clinical trials.","specificNumbers":"","methodology":"Researchers used high-fat diet-induced obese mice and treated them with tirzepatide, then analyzed white adipose tissue from two fat depots (perirenal and inguinal). RNA sequencing assessed transcriptional changes. Protein expression of browning markers was confirmed via immunoblotting and immunohistochemistry. In parallel in vitro experiments, differentiated 3T3-L1 adipocytes were treated with tirzepatide with or without the cAMP inhibitor SQ22536 to test whether cAMP signaling was required for the browning effect.","limitations":"This study was conducted in mice and cultured cells, not humans, so the fat-browning effect may not translate directly to human physiology. The abstract does not provide specific quantitative data for the degree of weight loss or fat mass reduction. While the cAMP pathway was identified as critical, other signaling pathways may also contribute. The study used a pharmacological inhibitor (SQ22536) rather than genetic approaches to confirm the mechanism, which can have off-target effects."},{"rthcId":"RPEP-16191","title":"Adaptive cationic peptide bundles hydrogel for the repair of infected mandibular defects.","authors":"Sun, Yimin; Yang, Xuetao; Liu, Yin; Zhang, Chenxi; Feng, Huiyu; Wu, Dongdong; Ye, Ling; Yu, Fanyuan; Li, Feifei","year":2026,"journal":"Biomaterials, 325, 123613","doi":"10.1016/j.biomaterials.2025.123613","pmid":"40818323","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16192","title":"Emerging landscape of bioinformatics and artificial intelligence applications in cell-penetrating peptide-based delivery.","authors":"Sun, Yu; Zhang, Muqing; Liu, Huiting; Wang, Hu","year":2026,"journal":"Expert opinion on drug delivery, 23(3), 495-515","doi":"10.1080/17425247.2025.2587940","pmid":"41206781","tags":["drug-delivery","cell-penetrating-peptides"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"AI and bioinformatics tools have dramatically accelerated the discovery and design of cell-penetrating peptides (CPPs). This systematic review covers computational tools developed between 2011 and 2025 that predict whether a peptide can cross cell membranes. These tools use various machine learning and AI algorithms to analyze peptide sequences and predict their cell-penetrating potential, replacing slow and expensive trial-and-error laboratory screening.\n\nThe review catalogs the landscape of available prediction tools, their underlying algorithms, strengths, and limitations. CPPs can deliver therapeutic cargo including small molecule drugs, proteins, and nucleic acids into cells, making them valuable for drug delivery, gene therapy, and molecular imaging. AI-driven design is enabling researchers to identify novel CPPs faster than ever before.","whyItMatters":"Finding peptides that can reliably cross cell membranes has traditionally required extensive laboratory testing. AI prediction tools are transforming this process, potentially identifying effective CPPs from sequence data alone in minutes rather than months. This review provides researchers with a practical guide to choosing the right computational tools for their CPP design projects, which could accelerate the development of peptide-based drug delivery systems for cancer therapy, gene therapy, and other applications.","specificNumbers":"Literature from 2011–October 2025 · 4 databases searched (PubMed, Embase, Scopus, Web of Science) · Multiple AI/ML algorithms reviewed · Applications: drug delivery, gene therapy, molecular imaging","methodology":"The authors conducted a systematic literature search across PubMed, Embase, Scopus, and Web of Science covering publications from 2011 to October 2025. They identified and reviewed bioinformatics tools and AI algorithms designed for peptide prediction, with particular focus on those predicting cell-penetrating potential. The review catalogs tool capabilities, algorithmic approaches, and practical applications.","limitations":"As a review, no new computational tools or experimental data are presented. The field is evolving rapidly, so tools published after October 2025 are not covered. Most AI prediction tools have been validated on limited datasets and may not generalize to all peptide types. The review does not provide head-to-head performance comparisons between tools on standardized benchmarks. Predicted cell-penetrating ability does not guarantee successful drug delivery in living systems."},{"rthcId":"RPEP-16193","title":"Integrating Metal-Organic Frameworks with Antimicrobial Peptides: Advances and Challenges in Antibacterial Therapeutics.","authors":"Sun, Yuxuan; Zhong, Hanyu; Wang, Yueqing; Zhang, Xiao; Cai, He; Chen, Junyu","year":2026,"journal":"ACS omega, 11(6), 8883-8896","doi":"10.1021/acsomega.5c09628","pmid":"41726623","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16194","title":"Discovery and molecular mechanism of a novel antihypertensive peptide from Chlamydomonas reinhardtii based on molecular docking, molecular dynamics simulation, in vitro, and in vivo analysis.","authors":"Suo, Qishan; Yue, Yang; Wang, Jing; Wu, Ning; Geng, Lihua; Zhang, Quanbin","year":2026,"journal":"Food research international (Ottawa, Ont.), 229, 118477","doi":"10.1016/j.foodres.2026.118477","pmid":"41763799","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"From eight protease hydrolysates of Chlamydomonas reinhardtii, the alkaline protease hydrolysate (CRPA) showed the strongest ACE inhibitory activity. The first ACE-inhibitory peptide identified from this microalga — a five-amino-acid sequence called IDYRY (ID-5) — had an IC50 of 18.54 ± 5.57 μM.\n\nID-5 was characterized as a noncompetitive ACE inhibitor, meaning it binds to the enzyme at a different site than the substrate. It demonstrated significant antihypertensive activity both in vitro and in spontaneously hypertensive rats (SHRs), with an effective dose corresponding to a human-equivalent dose of approximately 16 mg/kg/day. Molecular dynamics simulations revealed that ID-5 forms unique hydrogen bonds with Asp415 and Arg522 on ACE, a binding mechanism distinct from captopril or lisinopril.","whyItMatters":"ACE inhibitors are among the most widely prescribed medications for high blood pressure, but they can cause side effects like dry cough and angioedema. Discovering a food-derived peptide that inhibits ACE through a completely different binding mechanism opens the door to new therapeutic approaches with potentially different side effect profiles. Additionally, sourcing bioactive peptides from microalgae — which can be cultivated sustainably — aligns with growing interest in sustainable functional food ingredients.","specificNumbers":"","methodology":"Researchers prepared eight different protease hydrolysates from Chlamydomonas reinhardtii protein. ACE inhibitory activity was screened in vitro, and the most potent hydrolysate was tested in vivo using spontaneously hypertensive rats (SHRs). Bioassay-guided fractionation was used to isolate the active peptide. The peptide's binding mechanism was characterized through molecular docking and molecular dynamics simulation, and its inhibition type (noncompetitive) was determined through enzyme kinetics.","limitations":"The antihypertensive effect was demonstrated only in spontaneously hypertensive rats, not in humans. The IC50 value of 18.54 μM is moderate compared to pharmaceutical ACE inhibitors. Oral bioavailability, gastrointestinal stability, and absorption of the peptide in humans are unknown. The human-equivalent dose is an estimate based on animal scaling and has not been validated clinically. Molecular dynamics simulations model binding in silico and may not perfectly reflect in vivo conditions."},{"rthcId":"RPEP-16195","title":"In Vitro Antimycobacterial Activities of Short Peptide-Functionalized Silver Nanoparticle and Its In Silico Mechanistic Insight.","authors":"Suryakanta, Uday; Mishra, Sourav; Dhal, Ajit Kumar; Panigrahi, Bijayananda; Singh, Rohit Kumar; Mandal, Dindyal","year":2026,"journal":"ACS applied bio materials, 9(4), 2229-2249","doi":"10.1021/acsabm.5c02302","pmid":"41632906","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16196","title":"Pneumatosis intestinalis in a patient treated with a glucagon-like peptide-1 receptor agonist and prednisone.","authors":"Sutton, Stephanie; Ferguson, Quinn; Gimpelevich, Roman; Hemadeh, Ossama","year":2026,"journal":"JCEM case reports, 4(3), luag019","doi":"10.1210/jcemcr/luag019","pmid":"41743176","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16197","title":"The Diagnostic Challenges of Acute Myocarditis in a Patient with Fulminant Type 1 Diabetes and Transient Elevation of Anti-GAD Antibodies-A Case Report.","authors":"Swe, Thet Htar; Ren, Yan; Gong, Hongping; Li, Zhenyi; Lv, Qingguo; Ran, Xingwu; Wei, Xin; Wang, Chun","year":2026,"journal":"Journal of clinical medicine, 15(4)","doi":"10.3390/jcm15041553","pmid":"41753240","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16198","title":"Neuroimmunometabolism in Health and Disease.","authors":"Sweeney, Charles A P; Liu, Hanyu; Dean, Matthew; Domingos, Ana I","year":2026,"journal":"Annual review of immunology","doi":"10.1146/annurev-immunol-090122-050509","pmid":"41642198","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16199","title":"An Injection Leading to Oesophageal Perforation: A Rare Case of Contained Boerhaave's Syndrome Following Unsupervised GLP-1/GIP Receptor Agonist Dose Escalation.","authors":"Syed, Noor Sadiq; Oldfield, Thomas; Akash-Ul-Husnain, Syed; Moiz, Atif","year":2026,"journal":"Cureus, 18(1), e101811","doi":"10.7759/cureus.101811","pmid":"41717183","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16200","title":"Dual Amino Acid Swap in MUC7-Derived Peptide Enhances Resistance and Modulates Zn(II) and Cu(II) Complex Stability, Secondary Structure and Antimicrobial Activity.","authors":"Szarszoń, Klaudia; Kachnowicz, Jan; Janek, Tomasz; Domínguez-Martin, Alicia; Jezierska, Aneta; Wątły, Joanna","year":2026,"journal":"Inorganic chemistry","doi":"10.1021/acs.inorgchem.5c05849","pmid":"41781350","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16201","title":"Liganded LolCDE structures reveal a common substrate-LolE interaction guiding bacterial lipoprotein transport.","authors":"Szewczyk, Paul; Greene, Nicholas P; Symmons, Martyn F; Hardwick, Steven W; Koronakis, Vassilis","year":2026,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 123(4), e2520579123","doi":"10.1073/pnas.2520579123","pmid":"41557797","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16202","title":"Effect of liraglutide on subclinical atherosclerosis and cardiometabolic risk factors in adults with type 1 diabetes: A prospective pilot study.","authors":"Sánchez-García, David; Luna-Garza, Yesica; Saavedra-Castillo, Eloísa; Gómez-Martínez, Graciela; Diaz-Sallas, Marcelo; Ortega-Valdez, Alejandra Claudia; Martínez-Mendoza, Zinia Fernanda; Reyes-Valdez, Karina Rosa; Huitron-Ramirez, Rosa Alicia; Martinez-Rentería, Janeth Patricia; Rocha-Rojas, Ricardo; Dominguez-Rodriguez, Ana Livia; Garza-Davila, Kelly Danara; Quintanilla-Flores, Dania Lizet","year":2026,"journal":"Diabetic medicine : a journal of the British Diabetic Association, e70222","doi":"10.1111/dme.70222","pmid":"41693130","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16203","title":"FABP4, marker of worse prognosis in cardiovascular disease, induces neutrophil's proatherogenic phenotype which is modulated by semaglutide.","authors":"Sánchez-López, David; García-Vega, David; Viñuela, J E; Ferreirós-Vidal, Isabel; Iglesias-Álvarez, Diego; Martínez-Cereijo, José Manuel; Reija-López, Laura; Fernández-González, Ángel L; González-Juanatey, José R; Eiras, Sonia","year":2026,"journal":"Journal of molecular and cellular cardiology, 210, 12-27","doi":"10.1016/j.yjmcc.2025.10.009","pmid":"41183609","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16204","title":"Sustained glucagon-like peptide-1 receptor agonist treatment improves glycemic control and reduces all-cause mortality compared to dipeptidyl peptidase-4 inhibitors: A real-world target trial emulation in type 2 diabetes.","authors":"Sørensen, Kathrine Kold; Yazdanfard, Puriya Daniel Würtz; Zareini, Bochra; Wood-Kurland, Hannah Karin; Pedersen-Bjergaard, Ulrik; Andersen, Mikkel Porsborg; Michelsen, Jens; Imberg, Henrik; Lind, Marcus; Hallström, Sara; Lanzinger, Stefanie; Munch, Anders; Ohlendorff, Johan Sebastian; Gerds, Thomas Alexander; Torp-Pedersen, Christian","year":2026,"journal":"Diabetes, obesity & metabolism","doi":"10.1111/dom.70581","pmid":"41741950","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16205","title":"Potential role of a synthetic peptide hydrogel in accelerating mucosal defect healing: evidence from a porcine model.","authors":"Tachecí, Ilja; Šembera, Štěpán; Zimandlová, Dana; Morávková, Paula; Vejvalková, Kateřina Geisler; Radochová, Věra; Ryška, Aleš; Cyrany, Jiří","year":2026,"journal":"Surgical endoscopy, 40(2), 1549-1558","doi":"10.1007/s00464-025-12374-0","pmid":"41326730","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 84 lesions in 21 pigs, PuraStat-treated wounds showed significantly greater re-epithelialization-to-defect ratios versus controls (p = 0.03), particularly after EMR. Endoscopic measurements showed 33% mean wound size reduction in the PuraStat group (p = 0.001). Histopathological analysis of defect area reduction approached but did not reach significance (p = 0.055). No adverse events were observed. The effect was more pronounced in EMR-induced lesions than ESD-induced lesions.","whyItMatters":"Endoscopic resection of GI tumors is increasingly common, but post-procedural bleeding and poor wound healing remain significant complications, sometimes requiring repeat procedures or hospitalization. PuraStat is already CE-marked and used clinically for hemostasis during endoscopy. This study suggests an expanded role — not just stopping bleeding, but actively promoting wound healing — which could improve patient outcomes and reduce healthcare costs associated with post-procedural complications.","specificNumbers":"","methodology":"Prospective, randomized, evaluator-blinded preclinical study in 21 pigs. Each animal underwent 2 EMR and 2 ESD procedures in the esophagus and stomach (84 total lesions). Lesions were randomized to PuraStat or saline application. Healing was evaluated at 8 days via follow-up endoscopy, gross pathology, and histopathological analysis. Primary endpoint was re-epithelialization-to-defect ratio.","limitations":"This is an animal study in healthy pig tissue, which may not represent healing dynamics in diseased human tissue (e.g., tissue with prior radiation or chronic inflammation). The 8-day follow-up is short and doesn't capture complete healing. Endoscopic wound measurements have an estimated ±10% error margin. The histopathological difference between groups approached but did not reach statistical significance (p=0.055). The study was not powered for clinical outcomes like bleeding rates or stricture formation."},{"rthcId":"RPEP-16206","title":"Mapping the global research landscape of tirzepatide: a bibliometric analysis of trends, collaborations, and emerging themes in obesity and diabetes managements.","authors":"Taha, Manal Mohamed Elhassan; Abdelwahab, Siddig Ibrahim; Oraibi, Omar; Madkhali, Mohammed A; Alhazmi, Abdulhameed Albarraq; Jeraiby, Mohammed; Abdullah, Saleh M; Farasani, Abdullah; Moshi, Jobran M; Khamjan, Nizar A; Alshahrani, Saeed; Shubaily, Hussam M; Sahli, Khaled A; Qadri, Marwa; Khardali, Amani","year":2026,"journal":"Naunyn-Schmiedeberg's archives of pharmacology, 399(2), 2577-2591","doi":"10.1007/s00210-025-04574-1","pmid":"40900331","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16207","title":"Injection-site and dermatologic reactions associated with glucagon-like peptide-1 receptor agonists: Insights from meta-analysis of randomised controlled trials and real-world evidence.","authors":"Taj, Shifa; Zuber, Mohammed; Rashid, Muhammed; Chhabra, Manik; Undela, Krishna; Rawal, Smita; Villa Zapata, Lorenzo","year":2026,"journal":"Diabetes, obesity & metabolism, 28(3), 1956-1971","doi":"10.1111/dom.70382","pmid":"41395692","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16208","title":"Enhancement of the efficiency of a DNA vaccine construct harboring HSP70 mini-chaperones linked to HIV-1 Nef antigen using IL-7 cytokine and REV peptide.","authors":"Tajvidi, Neda; Bolhassani, Azam; Heshmati, Masoumeh; Naseroleslami, Maryam; Hosseini Shokouh, Seyyed Javad","year":2026,"journal":"Microbial pathogenesis, 212, 108293","doi":"10.1016/j.micpath.2026.108293","pmid":"41519445","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16209","title":"Migraine Management in Japan: Current Approaches and Science Narrative Including an Evidence-based Review.","authors":"Takeshima, Takao; Kikui, Shoji; Danno, Daisuke","year":2026,"journal":"Internal medicine (Tokyo, Japan), 65(1), 46-66","doi":"10.2169/internalmedicine.4846-24","pmid":"39694479","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16210","title":"Prognostic significance of subsequent decline in LVEF in heart failure with improved ejection fraction - A report from the CHART-2 study.","authors":"Takigahira, Takuya; Nochioka, Kotaro; Miyata, Satoshi; Shiroto, Takashi; Inoue, Takumi; Susukita, Kai; Hayashi, Hideka; Takahama, Hiroyuki; Takahashi, Jun; Shimokawa, Hiroaki; Yasuda, Satoshi","year":2026,"journal":"International journal of cardiology. Heart & vasculature, 62, 101877","doi":"10.1016/j.ijcha.2026.101877","pmid":"41630955","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16211","title":"Effectiveness and adherence in a tirzepatide-supported digital weight-loss programme in Australia: A real-world observational study.","authors":"Talay, Louis; Hom, Jason; Scott, Tamara; Ahuja, Neera","year":2026,"journal":"Diabetes, obesity & metabolism","doi":"10.1111/dom.70462","pmid":"41532325","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"At 6 months, 31.7% of the 4,309 enrollees met adherence criteria, with mean weight loss of 16.9% (±8.6; 98.0% achieved ≥5% reduction). At 12 months, 16.1% were adherent with mean weight loss of 22.7% (±7.2; 100% achieved ≥5% reduction). First-month weight loss was the strongest predictor of 6- and 12-month outcomes. Sustained weekly weight tracking and health coach messaging were strongly associated with retention and greater weight loss. Paradoxically, very frequent weight tracking in month one correlated with poorer outcomes. Side effects were common but mostly mild/moderate and did not predict dropout.","whyItMatters":"Clinical trials show tirzepatide can produce dramatic weight loss, but real-world results often differ. This is one of the largest real-world studies of tirzepatide in a digital health setting, revealing that while the drug delivers exceptional results for engaged users, the majority of people drop out within months. This adherence gap is the central challenge for translating peptide-based obesity treatments into population-level health improvements.","specificNumbers":"","methodology":"Retrospective observational study of all patients initiating tirzepatide through the Juniper AU digital weight-loss service between September 2024 and April 2025 (n=4,309). The cohort was predominantly female (92.9%), Caucasian (81.9%), mean age 41.5 years, mean BMI 32.9. Adherence required minimum medication orders plus weight entries at defined timepoints. Full cohort analysis used last observation carried forward imputation. Multivariable models identified predictors of outcomes.","limitations":"This is a retrospective observational study without a control group or randomization. The cohort was predominantly young, female, and Caucasian, limiting generalizability. The adherence definition required specific medication orders and weight entries, which may not capture all engaged users. Last observation carried forward imputation likely overestimates weight loss for dropouts. The digital weight-loss service context may not represent typical clinical care. Selection bias exists as participants self-selected into a commercial program."},{"rthcId":"RPEP-16212","title":"Enhanced antibacterial activity of antimicrobial peptide-antibiotic combinations against multidrug-resistant bacteria.","authors":"Talha, Muhammad; Roque-Borda, Cesar Augusto","year":2026,"journal":"FEMS microbes, 7, xtag003","doi":"10.1093/femsmc/xtag003","pmid":"41769086","tags":[],"studyType":"review","evidenceStrength":"moderate","keyFinding":"Combining antimicrobial peptides (AMPs) with conventional antibiotics produces synergistic antibacterial effects against multidrug-resistant (MDR) bacteria. The synergy works because AMPs disrupt bacterial membranes, which allows antibiotics to penetrate more effectively — essentially punching holes that let the drugs in. This combination approach can restore susceptibility to antibiotics that bacteria had become resistant to.\n\nThe review identifies key mechanisms driving this synergy: increased membrane permeability, enhanced porin-dependent antibiotic uptake, and immunomodulatory effects that boost the host's own defenses. However, significant translational barriers remain, including peptide instability, pharmacokinetic mismatches between AMPs and antibiotics, potential toxicity, and strain-dependent variability in whether synergy actually occurs.","whyItMatters":"Antibiotic resistance is one of the most serious global health threats, with MDR infections killing over a million people annually. AMPs alone haven't become viable drugs due to stability and toxicity issues. But using them as adjuncts — combination partners that make existing antibiotics work again — could breathe new life into the current antibiotic arsenal without requiring entirely new drug classes. This 'combination rescue' strategy is one of the most practical near-term approaches to the resistance crisis.","specificNumbers":"MDR bacteria resistance crisis as global threat · AMPs limited as monotherapy by instability, toxicity, and pharmacokinetics · Synergy via membrane permeabilization and porin-dependent uptake · Strain-dependent variability in synergistic responses","methodology":"This is a critical review integrating evidence from both in vitro and in vivo studies on AMP-antibiotic combination therapy. The authors examine the molecular mechanisms of synergy, determinants of successful combinations, and translational barriers to clinical implementation. The review provides a framework for rational design of combination therapies.","limitations":"Most evidence for AMP-antibiotic synergy comes from in vitro studies that don't account for host immune factors, tissue penetration, and pharmacokinetic complexity. Synergy is often strain-dependent — what works against one bacterial isolate may not work against another. No large-scale clinical trials have validated AMP-antibiotic combinations in humans. Peptide stability and manufacturing challenges remain unsolved for many AMP candidates."},{"rthcId":"RPEP-16213","title":"Comparing Telepharmacy to Conventional Pharmacy Care: An Economic Evaluation.","authors":"Tam, Sophia; Persaud, Vishwanauth; Wertheimer, Albert","year":2026,"journal":"Journal of pharmacy practice, 8971900261427109","doi":"10.1177/08971900261427109","pmid":"41685675","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16214","title":"The brain-skin connection: A narrative review of neuroendocrine and immune pathways.","authors":"Tan, Chang Chuen; Soh, Krystal Valerie; Wang, Eugene; Choi, Ellie Ci-En","year":2026,"journal":"JAAD international, 24, 112-123","doi":"10.1016/j.jdin.2025.10.008","pmid":"41393358","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16215","title":"Klotho-derived peptide 1 ameliorates hepatic fibrosis induced by αKlotho deficiency and liver injury.","authors":"Tan, Huishi; Huang, Wenshu; Luo, Hanying; Min, Wenjian; Zhang, Xiaoyao; Sun, Xiaoli; Lin, Enqing; Hong, Xue; Yang, Peng; Zhou, Lili; Liu, Youhua","year":2026,"journal":"International journal of biological sciences, 22(3), 1425-1439","doi":"10.7150/ijbs.122107","pmid":"41608630","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16216","title":"Characterization and deorphanization of RYamide signaling in Aedes aegypti: A potential regulator of hindgut-associated physiology.","authors":"Tan, Jinghan; Luong, Thomas; Paluzzi, Jean-Paul V","year":2026,"journal":"PloS one, 21(2), e0342341","doi":"10.1371/journal.pone.0342341","pmid":"41729976","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16217","title":"Tirzepatide mitigates thoracic aortic aneurysm and dissection by alleviating the loss of the contractile phenotype in vascular smooth muscle cells and reducing vascular inflammation.","authors":"Tan, Liao; Liu, Jie; Shi, Ruizheng; Liu, Yubo","year":2026,"journal":"Vascular pharmacology, 162, 107581","doi":"10.1016/j.vph.2026.107581","pmid":"41610999","tags":["glp-1","cardiovascular"],"studyType":"animal","evidenceStrength":"preliminary","keyFinding":"Tirzepatide dramatically reduced the formation of thoracic aortic aneurysm and dissection (TAAD) in mice — from 88.9% to 50.0% — and cut related deaths from 83.3% to 38.9%. The drug prevented pathological widening of the aorta in all three segments (ascending, arch, and descending) and preserved elastic fiber integrity.\n\nThe mechanism involved two key pathways: tirzepatide suppressed the NLRP3 inflammasome (reducing IL-1β, IL-6, and MCP-1 inflammation), and it prevented vascular smooth muscle cells from losing their contractile phenotype — a critical event in aneurysm development. In vitro experiments on human aortic smooth muscle cells confirmed that tirzepatide directly reversed the cellular changes that lead to weakened blood vessel walls.","whyItMatters":"Thoracic aortic aneurysm and dissection is a life-threatening emergency with no effective drug treatment — surgery is currently the only option to prevent fatal rupture. If tirzepatide (already FDA-approved for diabetes and weight loss) can also protect the aorta, it could be the first pharmacological therapy for this deadly condition, potentially repurposed from its existing metabolic indications.","specificNumbers":"TAAD incidence: 88.9% → 50.0% · Deaths: 83.3% → 38.9% · Tirzepatide 10 nmol/kg daily · 28-day model · Reduced IL-1β, IL-6, MCP-1 · NLRP3/caspase-1 downregulated","methodology":"Mouse model of TAAD induced by 28 days of BAPN (β-aminopropionitrile). Mice were divided into four groups: control, tirzepatide-only, BAPN (disease model), and BAPN plus tirzepatide. Tirzepatide was given daily at 10 nmol/kg via intraperitoneal injection. Outcomes included TAAD incidence, mortality, aortic diameter, histology (elastin, proteoglycan), inflammatory markers, and smooth muscle cell phenotype markers. In vitro experiments used PDGF-BB-stimulated human aortic smooth muscle cells to assess direct effects of tirzepatide on cellular phenotype switching.","limitations":"This is an animal study using a chemical-induced TAAD model, which may not fully replicate human aneurysm development. The BAPN model creates rapid, aggressive disease over 28 days — very different from the slow progression of human TAAD over years or decades. Tirzepatide was given via intraperitoneal injection at a specific dose; human dosing and subcutaneous delivery would differ. No long-term safety data for this vascular indication exists."},{"rthcId":"RPEP-16218","title":"Exploring the cardiopulmonary effects of tirzepatide in atrial fibrillation and comorbid chronic obstructive pulmonary disease.","authors":"Tan, Min Choon; Yee, Ming Fong; Vignarajah, Aravinthan; Pathangey, Girish; Abdelnabi, Mahmoud; DeSimone, Christopher V; Deshmukh, Abhishek J; Sorajja, Dan; El-Masry, Hicham; Lee, Justin Z","year":2026,"journal":"The American journal of medicine, 139(1), 108-113","doi":"10.1016/j.amjmed.2025.09.018","pmid":"40998187","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16219","title":"Comparison of cardiovascular outcomes between once-weekly semaglutide and dulaglutide in adults with type 2 diabetes and established atherosclerotic cardiovascular disease in the United States.","authors":"Tan, Xi; Liang, Yuanjie; Xie, Lin; Harton, Joanna; Gutierrez, Cynthia; Muhammad, Chalak; Swift, Caroline; de Havenon, Adam","year":2026,"journal":"Diabetes, obesity & metabolism","doi":"10.1111/dom.70440","pmid":"41508706","tags":["glp-1-receptor-agonists"],"studyType":"retrospective-cohort","evidenceStrength":"high","keyFinding":"Among 75,243 U.S. adults with type 2 diabetes and established atherosclerotic cardiovascular disease, semaglutide users had a 22% lower risk of major adverse cardiovascular events (MACE) compared to dulaglutide users (HR 0.78, 95% CI 0.70–0.87, p<0.001).\n\nMACE incidence rates were 25.7 per 1,000 person-years for semaglutide versus 33.0 for dulaglutide. After entropy balancing to account for baseline differences, all standardized mean differences were below 0.1, indicating well-matched cohorts.","whyItMatters":"While both semaglutide and dulaglutide are GLP-1 receptor agonists approved for type 2 diabetes, clinicians have lacked direct head-to-head cardiovascular outcome data comparing them. This large real-world study fills that gap, suggesting semaglutide offers meaningfully better heart protection in patients who already have cardiovascular disease — a finding that could influence prescribing decisions for millions of high-risk patients.","specificNumbers":"n=75,243 · HR 0.78 (95% CI 0.70–0.87) · p<0.001 · semaglutide MACE rate 25.7/1000 PY · dulaglutide MACE rate 33.0/1000 PY · 22% risk reduction","methodology":"Retrospective cohort study using Optum's de-identified Clinformatics Data Mart (Medicare claims data) from January 2007 through September 2024. Included new initiators of semaglutide (n=42,007) or dulaglutide (n=33,236) aged 18+ with both type 2 diabetes and established atherosclerotic cardiovascular disease. Entropy balancing was used to match cohorts on baseline characteristics. Primary outcome was 3-point MACE (stroke, MI, CV death), analyzed with doubly robust Cox proportional hazard models.","limitations":"As a retrospective claims-based study, it cannot establish causation and may be subject to residual confounding despite entropy balancing. Medicare claims data may not capture all cardiovascular events or deaths. The study cannot determine which specific dose of each drug patients received, and adherence patterns are unknown. It reflects a U.S. Medicare population, which may not generalize to younger or international populations."},{"rthcId":"RPEP-16220","title":"Endogenous cathelicidin protects against Toxoplasma gondii-associated liver damage.","authors":"Tan, Yi Lin; Cavalcante, Paloma; Cirone, Karina M; Fiorani, Franco; Young, Daniel; Dufour, Antoine; Finney, Constance; Cobo, Eduardo R","year":2026,"journal":"Infection and immunity, e0070825","doi":"10.1128/iai.00708-25","pmid":"41728969","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16221","title":"Association of GLP-1 receptor agonist use with psychiatric outcomes in adults with type 2 diabetes: a target trial emulation.","authors":"Tang, Huilin; Lu, Yiwen; Zhang, Bingyu; Zhang, Dazheng; Zhou, Ting; Chen, Jiajie; Lu, Ying; Lyu, Tianchu; Zheng, Kai; Chen, Yong","year":2026,"journal":"Diabetes research and clinical practice, 231, 113038","doi":"10.1016/j.diabres.2025.113038","pmid":"41386528","tags":["glp-1","mental-health","safety"],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"GLP-1 receptor agonists were not associated with increased risk of most psychiatric disorders compared to SGLT2 inhibitors or DPP-4 inhibitors in adults with type 2 diabetes. However, a modest association with anxiety disorder was observed. The study used target trial emulation — a rigorous real-world evidence method that mimics the design of a randomized clinical trial using observational data — to compare psychiatric outcomes across these three diabetes drug classes.","whyItMatters":"Reports of suicidal thoughts and other psychiatric symptoms in GLP-1 drug users have prompted FDA investigations and widespread concern. This study provides reassurance that GLP-1 drugs do not appear to increase the risk of most psychiatric conditions compared to other diabetes medications, though the anxiety signal warrants attention. This is particularly important given the millions of people now taking these drugs for diabetes and obesity.","specificNumbers":"","methodology":"Target trial emulation using real-world data — a method that designs an observational study to mimic a randomized controlled trial. Researchers compared psychiatric outcomes in adults with type 2 diabetes who initiated GLP-1 receptor agonists versus those who started SGLT2 inhibitors or DPP-4 inhibitors. The study assessed risk of various psychiatric disorders including anxiety.","limitations":"As an observational study (even with target trial emulation), residual confounding cannot be completely ruled out. The abstract is brief and does not detail the specific psychiatric outcomes assessed beyond anxiety, the exact population size, follow-up duration, or effect sizes. The study population was limited to adults with type 2 diabetes, so findings may not generalize to people taking GLP-1 drugs solely for obesity."},{"rthcId":"RPEP-16222","title":"Redox-Responsive Polymeric Nanocapsules for Enhanced Tumor-Targeted Delivery of Antimicrobial Peptides.","authors":"Tang, Lin; Li, Yajian; Lv, Xiaoyin; Guo, Jianmei; Zhang, Yijia; Lin, Yuqi; Nie, Kaili; Zeng, Jian; Zhang, Ming; Dai, Qiong","year":2026,"journal":"Advanced science (Weinheim, Baden-Wurttemberg, Germany), e74480","doi":"10.1002/advs.74480","pmid":"41709824","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16223","title":"Design and evaluation of dual-function antimicrobial peptides FPON for gram-negative bacteria with membrane disruption and translation inhibition abilities.","authors":"Tang, Yingqi; Liu, Jiye; Zhong, Wei; Tian, Jianan; Xie, Zhixiong; Zhong, Lipeng","year":2026,"journal":"mSphere, 11(1), e0039825","doi":"10.1128/msphere.00398-25","pmid":"41474833","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16224","title":"Comparative Efficacy and Safety of Different Orforglipron Doses in Patients With Type 2 Diabetes Mellitus and Obesity: A Systematic Review and Network Meta-Analysis.","authors":"Tantoush, Marwan; Almaghrabi, Yaseen; Abusbaeh, Allaeddin; Ahmed, Nouraddeen; Tantush, Ayoub; Ben Hamida, Bahaeddin; Sagher, Malek; Sager, Motasem; Abouslima, Aly; Elbahnasawy, Sara E; Elhady, Mahmoud M; Hesham Gamal, Mohamed","year":2026,"journal":"Cureus, 18(1), e102018","doi":"10.7759/cureus.102018","pmid":"41728423","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16225","title":"Targeting NPY5R-A Member of the NPY Receptor Family: Pharmacological and Transcriptomic Mechanisms of the Euphorbia Factor L2 Against Lung Adenocarcinoma.","authors":"Tao, Pengzhuo; Liu, Wei; Wang, Yongfu; Xue, Yajing; Liu, Changmin; Yuan, Yizhen; Leu, Kim Fey; Chen, Shilin; Song, Chi","year":2026,"journal":"Pharmaceuticals (Basel, Switzerland), 19(2)","doi":"10.3390/ph19020322","pmid":"41754862","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The study established NPY5R as a therapeutic target in lung adenocarcinoma through multiple lines of evidence:\n\n- High NPY5R expression in lung tumors correlated with poor patient prognosis\n- NPY5R expression was associated with immune cell infiltration in tumors\n- Euphorbia Factor L2 (EFL2) targeted NPY5R and inhibited A549 lung cancer cell proliferation and migration while inducing cell death (apoptosis)\n- Genetic knockdown of NPY5R further enhanced anti-tumor effects\n- Combining NPY5R knockdown with EFL2 treatment synergistically activated ECM, PI3K-Akt, and MAPK pathways\n- Four potential molecular targets downstream of NPY5R were identified via RNA sequencing","whyItMatters":"Lung adenocarcinoma is the leading cause of cancer deaths worldwide, and drug resistance limits current treatments. Identifying the neuropeptide Y receptor system as involved in cancer progression opens a completely new therapeutic avenue. NPY and its receptors are already well-studied in neuroscience and metabolism, meaning existing knowledge of this peptide system can be leveraged to accelerate cancer drug development targeting NPY5R.","specificNumbers":"","methodology":"The researchers used bioinformatics analyses to evaluate NPY receptor expression profiles and prognostic significance in lung adenocarcinoma. Experimental validation included lentivirus-mediated stable NPY5R knockdown in cancer cell lines, functional assays (CCK-8 proliferation, flow cytometry for apoptosis, scratch assays for migration), PRESTO-Tango receptor activation assays, RNA sequencing transcriptomic profiling, and qPCR validation.","limitations":"This is entirely a preclinical study using cell lines and bioinformatics — no animal tumor models or human clinical data are included. The compound EFL2 is plant-derived and not yet characterized for drug-like properties (bioavailability, toxicity, pharmacokinetics). The cell line work was primarily in A549 cells, and results may differ in other lung cancer subtypes. The bioinformatics prognosis data are correlative and don't prove causation. No clinical drugs targeting NPY5R currently exist."},{"rthcId":"RPEP-16226","title":"3, 2, 1! From GLP-2 to GLP-1 analog over a 10-year journey.","authors":"Tapia-Sanchiz, María Sara; Sampedro-Núñez, Miguel Antonio; Jiménez-Blanco, Sara; Molina-Baena, Begoña","year":2026,"journal":"Endocrinologia, diabetes y nutricion, 73(1), 501662","doi":"10.1016/j.endien.2025.501662","pmid":"41309330","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Teduglutide therapy in a patient with short bowel syndrome requiring home parenteral nutrition led to significant clinical and nutritional improvement: 70% reduction in parenteral nutrition requirements, spontaneous closure of enterocutaneous fistulas, and sufficient intestinal adaptation to enable surgical bowel reconstruction.\n\nFollowing surgery, the patient achieved full enteral autonomy — completely independent of intravenous nutrition. She later developed grade 1 obesity, highlighting the completeness of the nutritional recovery. The case demonstrates teduglutide's potential as a bridging therapy that can create conditions for surgical intervention and ultimate intestinal independence.","whyItMatters":"Short bowel syndrome is a devastating condition where patients cannot absorb enough nutrition from food and depend on intravenous feeding — often for life. Teduglutide is the first non-symptomatic treatment that can actually restore intestinal function. This case demonstrates its potential as a 'bridge to surgery' — improving the gut enough to enable surgical reconstruction that wasn't previously possible. The dramatic outcome — from IV nutrition dependence to full food independence — illustrates the transformative potential of GLP-2 peptide therapy.","specificNumbers":"","methodology":"Single patient case report documenting a 10-year clinical course of a 62-year-old woman with short bowel syndrome. The case tracks her progression from home parenteral nutrition dependence through teduglutide initiation, clinical response monitoring, surgical reconstruction, and achievement of full enteral autonomy.","limitations":"This is a single case report, which cannot establish generalizability. The specific surgical anatomy and SBS characteristics may have contributed to the favorable outcome. The 10-year timeframe involved multiple interventions, making it difficult to attribute all improvements solely to teduglutide. The development of obesity post-treatment raises questions about long-term management and metabolic consequences. Long-term safety data for extended teduglutide use remain limited."},{"rthcId":"RPEP-16227","title":"Outcomes of insulin treatment using an automated insulin delivery system from the onset of type 1 diabetes in pediatric patients-A 1-year retrospective, observational, two-center study.","authors":"Tarasiewicz, Mateusz; Chobot, Agata; Bielawska, Anna; Zając, Agnieszka; Polańska, Joanna; Jarosz-Chobot, Przemysława; Seget, Sebastian","year":2026,"journal":"Journal of diabetes investigation, 17(2), 227-233","doi":"10.1111/jdi.70184","pmid":"41439409","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16228","title":"Beyond weight loss: Effect of GLP-1 receptor agonist therapy on the urological health.","authors":"Tariq, Arisha; Garza Gangemi, Adrian; Herrera Caceres, Jaime","year":2026,"journal":"Urology case reports, 65, 103368","doi":"10.1016/j.eucr.2026.103368","pmid":"41716526","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16229","title":"Exploring the Structure-Activity Relationships and Molecular Mechanisms of Black Soldier Fly-Derived Antimicrobial Peptides with AI Insights.","authors":"Tariq, Muhammad Raheel; Wang, Hui; Liu, Shaojuan; Armenia, Ilaria; Tettamanti, Gianluca; Korai, Shakal Khan; Lin, Haiwen; Zheng, Chaozhong; Liang, Yanwen; Qin, Jianguang; Liu, Youming; Qasim, Muhammad; Ismail, Muhammad Asif; Wang, Fei","year":2026,"journal":"Insects, 17(2)","doi":"10.3390/insects17020207","pmid":"41752610","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16230","title":"Effective Non-Invasive Delivery of Epigenetic Drugs Using Functionalized Accessory Unit Conjugates.","authors":"Tashima, Toshihiko","year":2026,"journal":"Pharmaceutics, 18(1)","doi":"10.3390/pharmaceutics18010115","pmid":"41599222","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16231","title":"Resolution of severe lumbar spinal epidural lipomatosis following tirzepatide-induced weight loss: illustrative case.","authors":"Tazhibi, Masih; Liu, David D; Chalif, Joshua I; Ali, Rohaid; Chi, John H","year":2026,"journal":"Journal of neurosurgery. Case lessons, 11(4)","doi":"10.3171/CASE25886","pmid":"41587457","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A 35-year-old man with class II obesity (BMI 37.8) and severe lumbar spinal epidural lipomatosis (SEL) causing progressive neurogenic claudication was treated with tirzepatide instead of surgery. After one year of treatment, he lost approximately 60 pounds, experienced marked symptom resolution, and repeat MRI showed near-complete regression of the epidural fat deposits that had been compressing his spine.\n\nThis is the first reported case of pharmacological weight loss reversing SEL, eliminating the need for surgical decompression.","whyItMatters":"Spinal epidural lipomatosis typically requires surgery when conservative measures fail, carrying risks of complications and recovery time. This case demonstrates that tirzepatide — a dual GIP/GLP-1 peptide receptor agonist — may provide a non-surgical alternative by addressing the root cause (excess fat deposition) rather than just the structural consequence. This expands the known therapeutic potential of incretin-based peptide drugs beyond diabetes and general weight management.","specificNumbers":"1 patient · BMI 37.8 kg/m² · ~60 lbs weight loss · 1 year of tirzepatide · Near-complete epidural fat regression on MRI · Surgery avoided","methodology":"This was a single-patient case report. A 35-year-old man with symptomatic lumbar SEL and class II obesity was treated with tirzepatide after counseling. Clinical outcomes were assessed through symptom evaluation and repeat MRI imaging at approximately one year.","limitations":"This is a single case report — the lowest level of clinical evidence. It cannot establish causation (the weight loss, not tirzepatide specifically, may be the key factor), and results may not generalize to other patients. Long-term durability of the response is unknown, and it is unclear whether weight regain after stopping the medication would lead to SEL recurrence."},{"rthcId":"RPEP-16232","title":"Real-World Evidence on Weight Loss and Safety With Semaglutide in Obesity Telehealth: A Large Retrospective Cohort Study.","authors":"Tchang, Beverly; Broffman, Lauren; Manalac, Raoul; Chai, Sam; Samonas, Nicholas; Barnes, Melynda; Allison, David B","year":2026,"journal":"Obesity (Silver Spring, Md.), 34(3), 729-737","doi":"10.1002/oby.70120","pmid":"41367196","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16233","title":"The challenges of experimental pharmacology in identifying novel treatments for Parkinson's disease.","authors":"Teil, Margaux; Huot, Philippe","year":2026,"journal":"Current opinion in neurobiology, 97, 103164","doi":"10.1016/j.conb.2025.103164","pmid":"41570740","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review covers 16 drugs that entered Parkinson's clinical trials after preclinical evaluation, across four categories: L-DOPA-induced dyskinesia treatment (buspirone, JM-010, befiradol, mesdopetam, foliglurax, dipraglurant), parkinsonism treatment (tavapadon), disease modification (prasinezumab, cinpanemab, nilotinib, minzasolmin, exenatide, NLY01, liraglutide, lixisenatide, semaglutide). For each drug, the review examines whether preclinical efficacy translated to clinical outcomes and identifies factors that influenced translational success or failure.","whyItMatters":"The extremely high failure rate of Parkinson's drugs in clinical trials (despite preclinical success) wastes billions in development costs and delays treatments for patients. Understanding why animal predictions fail — and specifically how GLP-1 peptide agonists are performing in this translation — is critical for the field. GLP-1 drugs represent the most exciting disease-modification candidates in Parkinson's, and this review contextualizes their clinical potential within the broader translation challenge.","specificNumbers":"","methodology":"Narrative review covering the past five years of Parkinson's disease drug development, examining 16 drugs from preclinical animal model testing through clinical trial outcomes. Each drug is analyzed for how well animal models predicted clinical efficacy, with discussion of model selection, design optimization, and translational barriers.","limitations":"Narrative review focused primarily on the past five years, potentially missing earlier relevant data. The review covers translation from animal models to clinical trials but the clinical trials themselves are at various stages — not all have final results. The diverse mechanisms of the 16 drugs make direct comparisons of translational success difficult. The review primarily focuses on efficacy translation, with less attention to safety/tolerability translation failures."},{"rthcId":"RPEP-16234","title":"Exploratory real-world experience with GLP-1 receptor agonists vs. metformin in youth with new-onset type 2 diabetes: a single-center retrospective study.","authors":"Tejeji, Isaac; Zeier, Troy; Smith, Josephine A; Chang, Nancy T; Chao, Lily C","year":2026,"journal":"Journal of pediatric endocrinology & metabolism : JPEM, 39(1), 56-64","doi":"10.1515/jpem-2025-0493","pmid":"41204644","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16235","title":"Enteric glia, neuropeptides, and Parkinson's: impacts of calcitonin gene-related peptide on gut alpha synuclein.","authors":"Templeton, Hayley N; Lanser, Toby B; Tobet, Stuart A; Schwerdtfeger, Luke A","year":2026,"journal":"American journal of physiology. Gastrointestinal and liver physiology, 330(2), G73-G86","doi":"10.1152/ajpgi.00230.2025","pmid":"41401974","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16236","title":"GLP-1 receptor agonists in patients with MGUS: A real-world propensity-matched study.","authors":"Tentolouris, Anastasios; Ntanasis-Stathopoulos, Ioannis; Filippatos, Charalampos; Terpos, Evangelos; Kastritis, Efstathios; Duque, Ernesto Ruiz; Dimopoulos, Meletios-Athanasios; Gavriatopoulou, Maria; Briasoulis, Alexandros","year":2026,"journal":"European journal of clinical investigation, 56(1), e70140","doi":"10.1111/eci.70140","pmid":"41123105","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16237","title":"Obesity in Type 1 Diabetes: Moving Beyond the \"Lean\" Disease Paradigm to Understand Risk, Complications, and Treatment.","authors":"Tentolouris, Anastasios; Koufakis, Theocharis; Fousteris, Evangelos","year":2026,"journal":"Current obesity reports, 15(1)","doi":"10.1007/s13679-026-00693-9","pmid":"41721160","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16238","title":"Semaglutide and tirzepatide in prediabetes: Evidence for diabetes prevention and cardiovascular protection.","authors":"Tentolouris, Anastasios; Siafarikas, Christos; Ntanasis-Stathopoulos, Ioannis; Anastasiou, Ioanna A; Kalara, Eirini; Briasoulis, Alexandros","year":2026,"journal":"Primary care diabetes","doi":"10.1016/j.pcd.2026.01.003","pmid":"41565568","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16239","title":"A DYRK inhibitor ameliorates glucose homeostasis and increases incretin-producing cells in diabetic mice.","authors":"Terasaki, Michishige; Zhou, Qiao; Andersson, Olov; Yamagishi, Sho-Ichi","year":2026,"journal":"Journal of molecular endocrinology, 76(2)","doi":"10.1530/JME-25-0214","pmid":"41711307","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16240","title":"GLP-1RA and the risk of non-arteritic anterior ischaemic optic neuropathy in patients with type 2 diabetes: A population-based study.","authors":"Tesfaye, Helen; Paik, Julie M; Wexler, Deborah J; Hathaway, Jimena Tatiana; Yu, Elaine W; Freedman, Ariel; Rizzo, Joseph F; Patorno, Elisabetta","year":2026,"journal":"Diabetes, obesity & metabolism, 28(2), 1517-1528","doi":"10.1111/dom.70200","pmid":"41104517","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16241","title":"The role of LEAP2 on cognitive impulsivity after refeeding: evidence from a preclinical study in female mice and from patients with anorexia nervosa.","authors":"Tezenas du Montcel, Chloé; Hamelin, Héloïse; Lebrun, Nicolas; Duriez, Philibert; Ramoz, Nicolas; Gorwood, Philip; Viltart, Odile; Tolle, Virginie","year":2026,"journal":"Translational psychiatry","doi":"10.1038/s41398-026-03912-y","pmid":"41786704","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16242","title":"Development of nanobody-conjugated LL37 for synergistic therapy against MDR Acinetobacter baumannii.","authors":"Thaiprayoon, Apisitt; Oonanant, Worrapoj; Boonsilp, Siriphan; Submunkongtawee, Nonth; Longsompurana, Phoomintara; Moonmangmee, Duangtip; Riangrungroj, Pinpunya; Leelawattanachai, Jeerapond; Tabtimmai, Lueacha; Kruse, Andrew C; DeLisa, Matthew P; Havanapan, Phattara-Orn; Waraho-Zhmayev, Dujduan","year":2026,"journal":"mSphere, e0077925","doi":"10.1128/msphere.00779-25","pmid":"41649287","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16243","title":"Bioactive Phytoconstituents Targeting Energy Expenditure and Appetite to Combat Obesity: A Comprehensive Review.","authors":"Thapa, Gayatri; Barbhuiya, Pervej Alom; Pathak, Manash Pratim","year":2026,"journal":"Current nutrition reports, 15(1), 1","doi":"10.1007/s13668-025-00718-0","pmid":"41484835","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16244","title":"Roux-en-Y Gastric Bypass Compared to Glucagon-Like Peptide-1 Receptor Agonists is Associated with Lower Out-of-Pocket Costs in Insured Patients with Type 2 Diabetes and Obesity: A Matched Analysis Over Two Years.","authors":"Thiyagarajan, Sibi; Wall-Wieler, Elizabeth; Liu, Yuki; Zheng, Feibi; Edwards, Michael","year":2026,"journal":"Obesity surgery, 36(2), 376-385","doi":"10.1007/s11695-025-08467-3","pmid":"41484761","tags":[],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"Over two years, insured patients who had Roux-en-Y gastric bypass (RYGB) surgery paid $704 less in out-of-pocket healthcare costs than matched patients treated with GLP-1 receptor agonists (semaglutide or tirzepatide) for type 2 diabetes and obesity.\n\nIn the first year, costs were similar between groups ($2,301 for RYGB vs. $2,179 for GLP-1 RAs, p=0.15). But in the second year, RYGB costs dropped significantly to $1,277 while GLP-1 RA costs remained at $2,104 (p<0.01), driven by the ongoing prescription costs of the medications.","whyItMatters":"The debate over surgery versus GLP-1 drugs for obesity and diabetes often focuses on clinical outcomes. This study adds a critical financial dimension: while GLP-1 drugs avoid surgery, their ongoing costs accumulate and may exceed the one-time surgical expense within two years, placing a greater financial burden on patients.","specificNumbers":"n=1,012 matched pairs · Year 1: RYGB $2,301 vs GLP-1 $2,179 (p=0.15) · Year 2: RYGB $1,277 vs GLP-1 $2,104 (p<0.01) · 2-year difference: $704 lower for RYGB (p<0.01)","methodology":"Retrospective matched analysis using the 2017–2023 Merative claims database. 1,012 pairs of adults with severe obesity and type 2 diabetes were matched on demographics, obesity status, comorbidities, and baseline costs. One group had RYGB without GLP-1 RA use; the other received semaglutide or tirzepatide for at least 2 years without any bariatric surgery. Out-of-pocket costs (outpatient services, inpatient admissions, prescriptions) were compared at 1 and 2 years using paired t-tests.","limitations":"This is a retrospective claims analysis, not a randomized trial, so unmeasured confounders may influence results. The study only captures 2 years of follow-up — the cost gap may widen further over time, or surgical complications could emerge later. It also only measures direct patient costs, not total healthcare system costs or clinical outcomes."},{"rthcId":"RPEP-16245","title":"GLP-1 agonist-associated presentations to unscheduled care: An opportunistic pilot study.","authors":"Thomas, Oliver; Coulson, James Michael","year":2026,"journal":"British journal of clinical pharmacology, 92(1), 312-316","doi":"10.1002/bcp.70335","pmid":"41204831","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16246","title":"Metabolic, enterohepatic and gut microbial effects of atorvastatin in healthy men.","authors":"Thomasen, Martin; Misiakou, Maria-Anna; Li, Simone S; Rodriguez de Evgrafov, Mari Cristina; Lynggaard, Mads B; Kårhus, Martin L; Brønden, Andreas; Kornholt, Jonatan; Chávez-Talavera, Oscar; Tailleux, Anne; Staels, Bart; Descat, Amandine; Hartmann, Bolette; Wewer Albrechtsen, Nicolai J; Rehfeld, Jens F; Holst, Jens J; Vilsbøll, Tina; Ellegaard, Anne-Marie; Sommer, Morten O A; Sonne, David P; Knop, Filip K","year":2026,"journal":"Endocrine connections","doi":"10.1530/EC-25-0721","pmid":"41738774","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16247","title":"Effect of common diabetes medications on metabolic dysfunction-associated steatotic liver disease as measured by transient elastography and other metabolic parameters: A systematic review.","authors":"Thompson, Kathryn; Breaux, William; Miller, Lesley S; Nemeth, John; Koumtouzoua, Sarah; Travis, Natasha","year":2026,"journal":"Clinics and research in hepatology and gastroenterology, 50(3), 102784","doi":"10.1016/j.clinre.2026.102784","pmid":"41679467","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16248","title":"Mitochondria-derived peptides in liver disease: Emerging regulators of hepatic metabolism and therapeutic targets.","authors":"Thoudam, Themis; Zeng, Ge; Gao, Hui; Jiang, Yanchao; Huda, Nazmul; Yang, Zhihong; Ma, Jing; Liangpunsakul, Suthat","year":2026,"journal":"Hepatology communications, 10(2)","doi":"10.1097/HC9.0000000000000885","pmid":"41543486","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies three key mitochondria-derived peptide (MDP) families and their roles in liver health:\n\n- Humanin: The first discovered MDP; protects hepatocytes from stress-induced cell death (apoptosis) and modulates lipid metabolism, exerting hepatoprotective effects in fatty liver disease\n- MOTS-c: Activates AMPK (a master metabolic regulator), regulates nuclear gene expression, suppresses fibrotic and inflammatory signaling, and restores mitochondrial function in MASLD and fibrosis models\n- SHLPs (1-6): Particularly SHLP2, which enhances mitochondrial function, improves insulin sensitivity, supports glucose homeostasis, and mitigates oxidative stress\n\nMDPs work both inside cells (modulating mitochondrial activity, oxidative stress, apoptosis) and outside cells (autocrine, paracrine, endocrine signaling), establishing a novel paradigm where mitochondrial DNA function extends well beyond energy production.","whyItMatters":"Fatty liver disease (MASLD) affects about 30% of the global population and has limited treatment options. Mitochondrial dysfunction is central to its progression. Discovering that mitochondria produce their own protective peptides opens an entirely new therapeutic avenue — potentially treating liver disease by supplementing or enhancing the body's own mitochondrial defense system.","specificNumbers":"","methodology":"This is a narrative review published in Hepatology Communications synthesizing current research on mitochondria-derived peptides, their biological mechanisms, and their relevance to chronic liver diseases, particularly metabolic dysfunction-associated steatotic liver disease (MASLD).","limitations":"Most evidence for MDPs in liver disease comes from cell culture and animal models; human clinical data is very limited. The exact receptors and signaling pathways for many MDPs are still being identified. Therapeutic development faces challenges including peptide stability, delivery, and determining effective doses in humans. Interactions between different MDPs are not well understood."},{"rthcId":"RPEP-16249","title":"Advancing precision tumor therapy: Progress in targeted delivery of peptide-based nanomaterials from microenvironment to organelles.","authors":"Tian, Kexin; Sheng, Jiabao; Chen, Jiao; Zhang, Mingjun; Song, Jiarui; Wu, Manqing; Zhao, Yinan; Zhang, Shubiao","year":2026,"journal":"Materials today. Bio, 37, 102820","doi":"10.1016/j.mtbio.2026.102820","pmid":"41660126","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16250","title":"Lactic Acid Bacteria Bacteriocins: Classification, Biosynthesis, Health Benefits, and Strategies for Enhanced Efficacy.","authors":"Tian, Shuhua; Ma, Shaotong; Xia, Yujie; Huang, Ke","year":2026,"journal":"Journal of agricultural and food chemistry, 74(7), 5859-5871","doi":"10.1021/acs.jafc.5c14047","pmid":"41700423","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review provides a comprehensive overview of LAB-derived bacteriocins:\n\n- Classification updated into Classes I-III based on structure and genetics\n- Biosynthesis regulated by quorum sensing (bacterial communication) and two-component signaling systems\n- Health benefits extend beyond antimicrobial activity to include anti-cancer effects, achieved primarily through membrane disruption mechanisms\n- Production can be enhanced through metabolic engineering, synthetic biology, combination therapies, and novel purification methods\n- Key challenge: scaling production while maintaining efficacy and overcoming barriers to clinical translation","whyItMatters":"As antibiotic resistance threatens global health, naturally-produced antimicrobial peptides from food-grade bacteria offer a promising alternative. Bacteriocins are already proven safe through centuries of use in fermented foods, giving them a head start for clinical development compared to entirely novel antimicrobial compounds.","specificNumbers":"","methodology":"Narrative review synthesizing current literature on LAB bacteriocin classification, biosynthesis genetics, production regulation, health applications, and strategies for enhanced efficacy and production scale-up.","limitations":"Most bacteriocin research remains at preclinical stages. Challenges include low production yields, purification difficulties, peptide stability issues, narrow antimicrobial spectra for some classes, and limited clinical trial data. The transition from food preservation to therapeutic applications requires overcoming significant regulatory and manufacturing hurdles."},{"rthcId":"RPEP-16251","title":"Amphipathic N-terminal helices drive MLKL-mediated necroptosis through an antimicrobial peptide-like mechanism across evolution.","authors":"Tian, Xin; Jin, Xiaotong; Jiang, Shuai","year":2026,"journal":"Developmental and comparative immunology, 177, 105574","doi":"10.1016/j.dci.2026.105574","pmid":"41724341","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16252","title":"Comparison of the effects of natural, cultivated, and synthetic musk on preventing acute cerebral ischemia/reperfusion injury in rats.","authors":"Tianyu, Liang; Weiying, Liu; Huayang, Tang; Fu, Peng; Cheng, Peng; Xiaoqi, Pan","year":2026,"journal":"Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan, 46(1), 39-50","doi":"10.19852/j.cnki.jtcm.20250924.001","pmid":"41736421","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16253","title":"Metabolic Dysfunction-Associated Steatotic Liver Disease in Adults: A Review.","authors":"Tilg, Herbert; Petta, Salvatore; Stefan, Norbert; Targher, Giovanni","year":2026,"journal":"JAMA, 335(2), 163-174","doi":"10.1001/jama.2025.19615","pmid":"41212550","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16254","title":"Identification of semaglutide use through detection of U6 and U7 metabolites in human urine.","authors":"Timms, Mark; Bowen, Christopher; Steel, Rohan","year":2026,"journal":"Analytical and bioanalytical chemistry, 418(4), 1115-1124","doi":"10.1007/s00216-025-06263-7","pmid":"41364333","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16255","title":"Prospective Study of Appetitive Sensations after Metabolic and Bariatric Surgery Compared with Low-Calorie Diet.","authors":"Tolbert, Lelia; Borden, Sarah; Leskowitz, Jamie; Ramakrishnan, Rajasekhar; Reid, Tirissa; Krikhely, Abraham; Bessler, Marc; Korner, Judith","year":2026,"journal":"Obesity surgery","doi":"10.1007/s11695-025-08473-5","pmid":"41649786","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"At equivalent weight loss (~15% total weight loss):\n- Surgery: significant increases in postprandial fullness and decreases in hunger and prospective eating; diet: no significant changes\n- Food cravings decreased in both groups initially, but only surgery maintained reduced cravings at one year\n- Postprandial GLP-1 nearly doubled after surgery (p<0.0001) but did not change with LCD (p=0.34)\n- GLP-1 increase correlated with increased fullness after surgery (r=0.69, p=0.038)\n\nAt one year, surgery produced 30.2% total weight loss vs 14.6% for LCD (p<0.0001), consistent with the hormonal and appetite advantages documented at the equivalent weight loss timepoint.","whyItMatters":"This study provides direct evidence for why bariatric surgery outperforms dieting: it fundamentally changes the gut's hormonal response to food. The nearly two-fold increase in GLP-1 — the same hormone that semaglutide mimics — explains why surgery patients feel fuller and crave less. This insight bridges bariatric surgery and GLP-1 pharmacotherapy, showing they work through the same biological pathway, and explains why GLP-1 drugs can partially replicate surgery's metabolic benefits.","specificNumbers":"","methodology":"Prospective study comparing LCD (n=15 at T2, 12 at T3) and bariatric surgery (n=24 at T2, 15 at T3) groups. Appetite was assessed using visual analog scales (VAS) and the food craving inventory at baseline (T1), at equivalent weight loss (T2), and at one year (T3). Postprandial GLP-1 levels were measured by ELISA.","limitations":"Small sample sizes (15-24 per group at T2, with attrition to 12-15 at T3) limit statistical power and generalizability. The study was not randomized — participants self-selected into surgery or diet groups, introducing potential confounders. Only GLP-1 was measured, though other gut hormones (PYY, ghrelin, oxyntomodulin) also change after surgery. The specific surgical procedure(s) are not detailed in the abstract."},{"rthcId":"RPEP-16256","title":"Female Sexual Desire, Arousal, and Orgasmic Dysfunctions: A Systematic Review and Meta-Analysis of Treatment Options.","authors":"Toledo, Rafaela Germano; Winkelman, William D; Reyes-Gonzalez, Daniela; Bergeron, Sophie; Fladger, Anne; Hacker, Michele R; Anand, Mallika","year":2026,"journal":"Journal of minimally invasive gynecology, 33(1), 16-33.e3","doi":"10.1016/j.jmig.2025.06.004","pmid":"40543759","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Meta-analyses showed distinct benefits for each treatment modality. Mindfulness-based CBT significantly improved total Female Sexual Function Index (FSFI) scores and subscales for desire, arousal, and orgasm. Flibanserin improved total FSFI and the desire subscale. Bremelanotide improved total FSFI along with desire and arousal subscales.\n\nAll three treatments reduced distress as measured by the Female Sexual Distress Scale. No head-to-head studies comparing CBT to pharmacotherapy were identified. Of 36 included studies, 26 were randomized controlled trials and 10 were single-arm trials.","whyItMatters":"Female sexual dysfunction affects a significant proportion of women but remains undertreated and under-discussed. This review provides the first comprehensive comparison across both behavioral and pharmacological treatments, giving clinicians — particularly gynecologists who are often the first point of care — evidence-based guidance for choosing among available treatment options.","specificNumbers":"","methodology":"Systematic review and meta-analysis following standard methodology. Researchers searched MEDLINE, Embase, Web of Science, Cochrane Library, PsycINFO, and ClinicalTrials.gov through December 2024. From 8,994 abstracts screened, 278 full-text articles were reviewed, and 36 studies met inclusion criteria. Two independent reviewers conducted each phase. Included studies had to assess female sexual dysfunction of desire, arousal, or orgasm using validated outcome measures (FSFI and FSDS).","limitations":"No studies directly compared CBT to pharmacotherapy, making cross-modality comparisons indirect. Most treatments other than the three meta-analyzed had too few studies to draw conclusions. The field is hampered by heterogeneous terminology for sexual dysfunction disorders and varying outcome measures across studies. Studies including sexual pain conditions were excluded, limiting generalizability."},{"rthcId":"RPEP-16257","title":"Calculating cost per event avoided using a composite number needed to treat.","authors":"Toliver, Joshua; Wang, Julia; Bhavsar, Jigish; Sullivan, Sean D","year":2026,"journal":"Journal of medical economics, 29(1), 242-248","doi":"10.1080/13696998.2026.2615606","pmid":"41562647","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16258","title":"Primary Care Providers Perspectives of GLP-1 Receptor Agonists to Manage Recurrent Weight Gain after Metabolic Bariatric Surgery - a Qualitative Study.","authors":"Tolvanen, Liisa; Mossberg, Karin; Grace, Lindsey M; Standen, Erin C; Phelan, Sean M; Andersson, Daniel P; Koball, Afton M","year":2026,"journal":"Obesity surgery, 36(1), 193-203","doi":"10.1007/s11695-025-08408-0","pmid":"41299124","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16259","title":"Long-Term Cardiovascular Outcomes of Glucagon-Like Peptide-1 Receptor Agonists in Non-diabetic Obesity: A Systematic Review and Meta-Analysis.","authors":"Tom-Ayegunle, Kehinde; Tom-Ayegunle, Olaoluwa; Okoye, Stella; Chukwuemeka, Uche; Adeyina, Tolulope S; Babarinde, Abdulraheem; Eleam, Uchenna","year":2026,"journal":"Cureus, 18(1), e100947","doi":"10.7759/cureus.100947","pmid":"41658748","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16260","title":"Untangling obese asthma: Design of proof-of-concept study of semaglutide in poorly controlled asthma.","authors":"Tomasello, Alessandra; Bacharier, Leonard B; Becker, Patrice M; Dempsey, Caeden; Wu, Pingsheng; Peebles, R Stokes; Niswender, Kevin; Dupont, William D; Bernard, Gordon; Cahill, Katherine N","year":2026,"journal":"The journal of allergy and clinical immunology. Global, 5(2), 100627","doi":"10.1016/j.jacig.2025.100627","pmid":"41567689","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16261","title":"Comparative long-term outcomes of anatomical and physiological repair for corrected transposition.","authors":"Tominaga, Yuji; Takeshita, Masashi; Watanabe, Takuji; Shibagaki, Keisuke; Nakamizo, Masaya; Kurosaki, Kenichi; Shiraishi, Isao; Iwai, Shigemitsu","year":2026,"journal":"European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery","doi":"10.1093/ejcts/ezag125","pmid":"41832963","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16262","title":"Critical evaluation of real-world evidence of repurposable medicines in the Alzheimer's disease drug development pipeline using a target trial emulation.","authors":"Tonegawa-Kuji, Reina; Karavani, Ehud; Danziger, Michael; Zhang, Pengyue; Hou, Yuan; Zhou, Yadi; Bykova, Marina; Pieper, Andrew A; Rosen-Zvi, Michal; Cummings, Jeffrey; Cheng, Feixiong","year":2026,"journal":"Alzheimer's & dementia (New York, N. Y.), 12(1), e70193","doi":"10.1002/trc2.70193","pmid":"41473419","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16263","title":"Using Artificial Intelligence to Assess Treatment-Effect Heterogeneity in Pragmatic Cardiovascular Trials: Insights from TRANSFORM-HF.","authors":"Tong, Guangyu; Li, Changjun; Li, Fan; Zeng, Yukang; Greene, Stephen J; Anstrom, Kevin J; Testani, Jeffrey; Mentz, Robert J; Velazquez, Eric J","year":2026,"journal":"medRxiv : the preprint server for health sciences","doi":"10.64898/2026.01.16.26344310","pmid":"41646819","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16264","title":"Metabolic Improvement Mediates the Causal Relationship Between GLP-1 Receptor Agonists and Myocardial Infarction: A Mendelian Randomization and Mediation Analysis Study.","authors":"Tong, Jingkai; Li, Nana; Hu, Fang; Yue, Yingying","year":2026,"journal":"Diabetes care, 49(1), 171-178","doi":"10.2337/dc25-1822","pmid":"41259721","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Higher GLP-1 receptor expression (genetically proxying GLP-1RA use) was causally associated with lower risk of type 2 diabetes (OR 0.94, 95% CI 0.92–0.97) and myocardial infarction (OR 0.97, 95% CI 0.95–1.00).\n\nMetabolic improvements mediated the MI protection:\n- HbA1c: 36.67% of the effect (95% CI 3.89–69.44%)\n- BMI: 28.86% (95% CI 2.62–55.10%)\n- Triglycerides: 18.52% (95% CI 1.47–35.57%)\n- HDL-cholesterol: 18.28% (95% CI 1.45–35.12%)\n- Systolic blood pressure: 11.55% (95% CI 0.33–22.76%)\n\nCritically, multivariate MR adjusting for all metabolic traits showed no direct effect of GLP-1R expression on MI (β = -0.003, P = 0.12), meaning the cardiovascular benefit is fully mediated through metabolic improvements.","whyItMatters":"With GLP-1 drugs prescribed to tens of millions of people, understanding exactly how they protect the heart is critical for clinical practice. This study settles a major debate: the heart attack protection comes from metabolic improvements, not a mysterious direct cardiac effect. This means clinicians should focus on maximizing metabolic targets (blood sugar, weight, lipids, blood pressure) when prescribing GLP-1 drugs for cardiovascular benefit — and patients who don't achieve metabolic improvement may not get heart protection.","specificNumbers":"","methodology":"The study used Mendelian randomization (MR), which uses genetic variants as natural 'randomizers' to infer causal relationships. Genetic variants associated with GLP-1 receptor expression served as instrumental variables proxying GLP-1RA use. Two-step MR quantified how much of the MI protection was mediated by each metabolic trait. Multivariate MR adjusted for all metabolic mediators simultaneously to test for direct effects. GWAS data came from the Million Veteran Program (metabolic traits), DIAGRAM consortium (T2DM), and UK Biobank/CARDIoGRAMplusC4D (MI), all restricted to European ancestry.","limitations":"Mendelian randomization uses genetic variants that reflect lifelong exposure, which may differ from the effects of starting GLP-1 drugs in middle age. The analysis was restricted to European ancestry, limiting generalizability. GLP-1R expression variants may not perfectly proxy the pharmacological effects of GLP-1RAs. The confidence intervals for some mediation estimates are wide. MR cannot account for all potential pleiotropy (genetic variants affecting outcomes through unintended pathways)."},{"rthcId":"RPEP-16265","title":"The comparative efficacy of SGLT-2 inhibitors and GLP-1 receptor agonists on metabolic benefits in T2DM patients: a systematic review and network meta-analysis.","authors":"Tong, Jingkai; Li, Nana; Hu, Fang; Yue, Yingying","year":2026,"journal":"European journal of medical research, 31(1)","doi":"10.1186/s40001-026-03986-w","pmid":"41620788","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16266","title":"Progression to type 2 diabetes among post-myocardial infarction patients with overweight or obesity: a real-world cohort study.","authors":"Tonnesen, Pernille Tilma; Olesen, Kevin Kris Warnakula; Gyldenkerne, Christine; Hansen, Malene Kaerslund; Stødkilde-Jørgensen, Nina; Thrane, Pernille Gro; Andersen, Malene Højgaard; Poulsen, Per Løgstrup; Thomsen, Reimar Wernich; Sattar, Naveed; Sørensen, Henrik Toft; Maeng, Michael","year":2026,"journal":"Cardiovascular diabetology, 25(1), 56","doi":"10.1186/s12933-026-03085-4","pmid":"41580697","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16267","title":"The Effect of GLP-1 Agonists on Patients with Metabolic-Associated Steatotic Liver Disease: A Systematic Review and Meta-Analysis.","authors":"Tornea, Denisia Adelina; Goldis, Christian; Isaic, Alexandru; Motofelea, Alexandru Catalin; Sima, Alexandra Christa; Ciocarlie, Tudor; Crintea, Andreea; Diaconescu, Razvan Gheorghe; Motofelea, Nadica; Goldis, Adrian","year":2026,"journal":"Pharmaceutics, 18(1)","doi":"10.3390/pharmaceutics18010086","pmid":"41599194","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 agonists were associated with a statistically significant 3-fold increase in resolution of MASH without worsening fibrosis (RR 3.03, p<0.05) compared to controls. They also significantly improved liver fibrosis, weight loss, HbA1c, and alanine aminotransferase levels (SMD -0.54, p=0.008).\n\nImportantly, in patients without type 2 diabetes, GLP-1 agonists showed no significant effect on weight loss (SMD -0.97, p=0.12) or fibrosis improvement (RR 1.54, p=0.24). Overall adverse events were slightly higher with GLP-1 agonists (RR 1.10, p<0.05), but serious adverse events were comparable between groups.","whyItMatters":"MASLD affects roughly a quarter of the global population and can progress to cirrhosis and liver cancer, yet effective pharmacological treatments have been limited. This meta-analysis provides the strongest evidence to date that GLP-1 peptide therapies can resolve liver inflammation and improve fibrosis, positioning them as a potential first-line treatment — especially for the large population of patients who have both fatty liver disease and type 2 diabetes.","specificNumbers":"","methodology":"This was a systematic review and meta-analysis of 20 randomized parallel controlled trials identified through PubMed, Scopus, and Web of Science (searched October 2025). Study quality was assessed using Cochrane ROB2. Analysis was performed in RevMan 5.4 with subgroup analyses based on diabetes status, control group type, and GLP-1 agonist class (single, dual, or triple agonists).","limitations":"There was heterogeneity across the 20 included studies in terms of GLP-1 agonist type, dosing, treatment duration, and patient populations. The number of studies in non-diabetic patients was limited, making conclusions for that subgroup preliminary. Some outcomes had incomplete data across studies. The slightly higher overall adverse event rate needs consideration. Publication bias cannot be fully excluded. The analysis groups single, dual, and triple agonists together, which may obscure differences between drug classes."},{"rthcId":"RPEP-16268","title":"Glucagon-like peptide-1 receptor agonists in pediatric metabolic dysfunction-associated steatotic liver disease.","authors":"Tou, Andrea M; Panganiban, Jennifer","year":2026,"journal":"Journal of pediatric gastroenterology and nutrition, 82(1), 146-155","doi":"10.1002/jpn3.70242","pmid":"41144868","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16269","title":"GLP1R and OCT1 variants modulate semaglutide and metformin response in type 2 diabetes.","authors":"Tourtourikov, Ivan; Kalinkova, Maria; Ivanov, Peter; Mileva-Popova, Rene; Tafradjiiska-Hadjiolova, Radka; Handjieva-Darlenska, Teodora; Kadiyska, Tanya","year":2026,"journal":"Pharmacogenetics and genomics, 36(1), 9-17","doi":"10.1097/FPC.0000000000000577","pmid":"40996853","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Over three months, oral semaglutide 14 mg (n=10) significantly outperformed metformin XR 2000 mg (n=17) for weight loss: -6.5 ± 3.6 kg vs. -1.6 ± 2.5 kg (95% CI: -7.6 to -2.2; P=0.001). BMI reduction was also superior: -2.0 ± 1.2 vs. -0.3 ± 0.9 kg/m² (P=0.001).\n\nGenetic findings (exploratory):\n- OCT1 rs34130495 was associated with HDL cholesterol change in metformin-treated participants (β=+0.340 mmol/L per minor allele; P=0.0026; q=0.063 at 10% FDR)\n- GLP1R rs6923761 showed nominal trends for weight and BMI change in semaglutide users (P≈0.06-0.07) but did not survive FDR correction\n\nThe authors describe these as hypothesis-generating data supporting the feasibility of genotype-guided diabetes treatment studies.","whyItMatters":"As GLP-1 drugs like semaglutide become first-line treatments for millions of patients, understanding why some people respond better than others is increasingly important. Pharmacogenomics — using genetic testing to predict drug response — could help clinicians choose the right medication for each patient from the start. While this study is too small to draw firm conclusions, it demonstrates that genotype-guided studies are feasible even in local clinical settings and identifies specific gene variants worth testing in larger populations.","specificNumbers":"","methodology":"Twenty-seven Bulgarian adults with type 2 diabetes (BMI ≥25 kg/m², mean HbA1c 8.3 ± 0.9%) received either metformin XR 2000 mg (n=17) or oral semaglutide 14 mg (n=10) for three months. Three common genetic polymorphisms were genotyped by Sanger sequencing: SLC22A1 rs628031, SLC47A1 rs2252281, and GLP1R rs6923761. Primary endpoints were 3-month changes in weight and HbA1c. ANOVA and ordinary least squares regression assessed genotype and treatment effects, with covariate-adjusted linear models.","limitations":"The sample size is very small (27 total; only 10 on semaglutide), severely limiting statistical power for genetic associations. The genetic findings did not survive multiple comparison correction (FDR). This was not a randomized trial — treatment assignment was clinical, introducing potential selection bias. Only three genetic variants were tested; comprehensive pharmacogenomic profiling was not performed. The 3-month follow-up is short. The single-ethnicity (Bulgarian) cohort limits generalizability. HbA1c results are not reported in the abstract."},{"rthcId":"RPEP-16270","title":"Invasive Confirmation of Microvascular Recovery Parallel to Left Ventricular Functional Restoration.","authors":"Toya, Takumi; Kondo, Takumi; Sekine, Otoya; Aoyama, Masayuki; Sumida, Nayuka; Nishimura, Takafumi; Miyazaki, Yoshichika; Inagawa, Kohei; Sakamoto, Munehisa; Momiyama, Yukihiko","year":2026,"journal":"JACC. Case reports, 107008","doi":"10.1016/j.jaccas.2026.107008","pmid":"41860489","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16271","title":"Evaluation of Nile Tilapia (Oreochromis niloticus) Skin Peptides for Wound Healing: A Systematic and Meta-Analysis Review.","authors":"Tozetto, Rodrigo; de Macedo, Julia B; da Silva, Thais Leticia M; Ventura, Ana Carolina T; Beltrame, Flávio Luís; Ferrari, Priscileila C","year":2026,"journal":"ACS biomaterials science & engineering, 12(1), 53-70","doi":"10.1021/acsbiomaterials.5c01219","pmid":"41329667","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16272","title":"Amygdalar calcitonin gene-related peptide driven effects of cold sensitivity induced by peripheral neuropathy in mice.","authors":"Trail, Alexis D; Allen, Heather N; Paul, Blesson; Nelson, Tyler S; Widner, James A; Lewter, Lakeisha; Tack, See H; Neilan, Rachael Miller; Kolber, Benedict J","year":2026,"journal":"The journal of pain, 41, 106199","doi":"10.1016/j.jpain.2026.106199","pmid":"41577217","tags":[],"studyType":"animal study","evidenceStrength":"low","keyFinding":"CGRP in the amygdala — a brain region critical for pain processing — selectively modulated cold sensitivity but not mechanical sensitivity in two mouse models of neuropathic pain. Infusing CGRP into the amygdala reduced cold sensitivity in nerve injury (SNI) and chemotherapy-induced (paclitaxel) neuropathy models, while blocking CGRP with the antagonist CGRP 8-37 increased cold sensitivity. Notably, the effects were complex: they depended on which side of the brain was injected, which paw was tested, and whether the neuropathy was caused by nerve injury or chemotherapy. CGRP had no effect on mechanical pain sensitivity in either model.","whyItMatters":"CGRP is well-known as a pain mediator in migraine, but its role in neuropathic pain (chronic pain from nerve damage) is much less understood. This study reveals that CGRP in the amygdala actually reduces cold pain sensitivity — the opposite of what might be expected from a pain-promoting peptide. This suggests CGRP plays different, even opposing, roles depending on where in the nervous system it acts and what type of pain is involved. Understanding these nuances is critical for developing CGRP-based therapies that don't inadvertently worsen certain types of chronic pain.","specificNumbers":"2 neuropathy models (SNI + paclitaxel) · CGRP and CGRP 8-37 tested · Left and right amygdala injections · Cold sensitivity modulated · Mechanical sensitivity unchanged","methodology":"Researchers used two mouse models of neuropathic pain: spared nerve injury (SNI, surgical) and chemotherapy-induced peripheral neuropathy (CIPN, paclitaxel). They infused CGRP or the CGRP receptor antagonist CGRP 8-37 directly into the left or right central nucleus of the amygdala (CeA). Mechanical sensitivity was measured using von Frey filaments and cold sensitivity using the topical acetone drop assay on both hindpaws.","limitations":"This is a mouse study using direct brain infusion — a technique that doesn't translate to practical clinical drug delivery. The effects were complex and hemisphere/model-dependent, making interpretation challenging. Sample sizes per group are not specified. The study only examined acute effects of CGRP infusion, not chronic administration. The two neuropathy models may not fully represent the diversity of human neuropathic pain conditions."},{"rthcId":"RPEP-16273","title":"Modelling G protein-biased agonism using GLP-1 receptor C-terminal mutations.","authors":"Tran, Hanh Duyen; Zuo, Yiming; Wong, Carissa; Pollard, Alice; Bloom, Steve; Jones, Ben","year":2026,"journal":"Molecular metabolism, 105, 102321","doi":"10.1016/j.molmet.2026.102321","pmid":"41570980","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16274","title":"18 F-FDG PET/CT Five Days Post First Administration of Semaglutide : Side Effects in One Shot.","authors":"Triumbari, Elizabeth Katherine Anna; Lorusso, Margherita; Cirillo, Fiammetta; D'Orso, Francesca; Lolli, Vanessa; De Rosa, Alessandra; Di Carmine, Raffaela; Meduri, Guido Maria","year":2026,"journal":"Clinical nuclear medicine","doi":"10.1097/RLU.0000000000006360","pmid":"41650160","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16275","title":"Role of endogenous incretin hormones, GLP-1 and GIP, in cardiovascular physiology.","authors":"Trivedi, Khushali; Dolinsky, Vernon W","year":2026,"journal":"Canadian journal of physiology and pharmacology, 104, 1-13","doi":"10.1139/cjpp-2025-0163","pmid":"41549356","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16276","title":"Taking back control: The experience of adults using semaglutide and tirzepatide for obesity treatment - A qualitative study.","authors":"Trocchio, Lauren Lynn; Peters, Fredrick","year":2026,"journal":"Obesity pillars, 17, 100237","doi":"10.1016/j.obpill.2025.100237","pmid":"41399811","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16277","title":"Alpha-to-beta cell crosstalk: Adaptive mechanisms shaping islet function.","authors":"Tröster, Philip; Visa, Montse; Berggren, Per-Olof","year":2026,"journal":"Advances in biological regulation, 99, 101121","doi":"10.1016/j.jbior.2025.101121","pmid":"41067947","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16278","title":"Feasibility of recent peptide therapy for ischemic stroke: a comprehensive exploration.","authors":"Tseng, Kuo-Feng; Tseng, Kuo-Wei; Liao, Hsien-Yin; Chen, Pei-Hsien","year":2026,"journal":"Journal of pharmacological sciences, 160(1), 1-11","doi":"10.1016/j.jphs.2025.10.007","pmid":"41390189","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16279","title":"Network meta-analysis on efficacy of nerve stimulation or modulation in patients with heart failure.","authors":"Tseng, Ping-Tao; Zeng, Bing-Yan; Hsu, Chih-Wei; Hung, Chao-Ming; Stubbs, Brendon; Chen, Yen-Wen; Chen, Tien-Yu; Lei, Wei-Te; Chen, Jiann-Jy; Shiue, Yow-Ling; Liang, Chih-Sung","year":2026,"journal":"Heart rhythm, 23(3), 623-631","doi":"10.1016/j.hrthm.2025.04.004","pmid":"40204010","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16280","title":"Effectiveness of GLP-1 RAs in Restoring Normoglycemia in Patients With Prediabetes: An Updated Systematic Review and Meta-Analysis.","authors":"Tsironikos, Georgios I; Tsolaki, Vasiliki; Zakynthinos, George; Rammou, Vasiliki; Kyprianidou, Despoina; Antonogiannis, Thomas; Zakynthinos, Epameinondas; Bargiota, Alexandra","year":2026,"journal":"Diabetes/metabolism research and reviews, 42(1), e70114","doi":"10.1002/dmrr.70114","pmid":"41398448","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16281","title":"Nonmyeloablative Allogeneic Stem Cell Transplantation With Postcyclophosphamide in a Case of Acute Lymphoblastic Leukemia Complicated by Ventricular Septal Defect.","authors":"Tsutsumi, Yutaka; Ito, Shinichi; Suzuki, Toma; Kikuchi, Ryo; Aoyagi, Hiroyuki; Gibo, Hiroyuki; Teshima, Takanori","year":2026,"journal":"Transplantation proceedings","doi":"10.1016/j.transproceed.2026.01.002","pmid":"41654429","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16282","title":"VEGF Mimetic Peptide-Modified Bifunctional Nanosystem for Targeted Drug Delivery in Myocardial Infarction.","authors":"Tuerhan, Maisituremu; Tian, Hailan; Lu, Qinyi; Chen, Yaning; Wang, Zicheng; Aihemaitijiang, Aikeda; Meng, Yan; Wang, Yuji; Zheng, Yuanyuan","year":2026,"journal":"ACS applied bio materials, 9(4), 1998-2009","doi":"10.1021/acsabm.5c01922","pmid":"41641879","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16283","title":"Central liver-expressed antimicrobial peptide 2 induces anxiety- and depression-related behaviors and activates the hypothalamic-pituitary-adrenal axis in male mice.","authors":"Tufvesson-Alm, Maximilian; Jerlhag, Elisabet","year":2026,"journal":"Hormones and behavior, 179, 105905","doi":"10.1016/j.yhbeh.2026.105905","pmid":"41747667","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16284","title":"Immune activation by Ziziphus jujuba in Galleria mellonella: challenge-specific and temporal dynamics of humoral immune responses.","authors":"Turgut Genç, Tülay; Kaya, Serhat; Günay, Melih","year":2026,"journal":"Bulletin of entomological research, 1-13","doi":"10.1017/S000748532510076X","pmid":"41492842","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16285","title":"Kidney and Survival Outcomes with Semaglutide by Chronic Kidney Disease Severity in the FLOW Trial.","authors":"Tuttle, Katherine R; Mann, Johannes F E; Mayrdorfer, Manuel M; Rayner, Brian; Pugliese, Giuseppe; Pratley, Richard E; Perkovic, Vlado; Mahaffey, Kenneth W; Kashihara, Naoki; Jeppesen, Ole K; Gumprecht, Janusz; Correa-Rotter, Ricardo; Cherney, David Z I; Bosch-Traberg, Heidrun; Arici, Mustafa; Rossing, Peter","year":2026,"journal":"Clinical journal of the American Society of Nephrology : CJASN","doi":"10.2215/CJN.0000000974","pmid":"41706532","tags":[],"studyType":"randomized-controlled-trial","evidenceStrength":"very-high","keyFinding":"In this subgroup analysis of the landmark FLOW trial (3,533 participants, median 3.4-year follow-up), once-weekly semaglutide 1 mg reduced the primary composite kidney outcome by 24% (HR 0.76, 95% CI 0.66-0.88) and all-cause death by 20% (HR 0.80, 95% CI 0.67-0.95) compared to placebo in people with type 2 diabetes and chronic kidney disease.\n\nCritically, these benefits were consistent across the full spectrum of CKD severity — from milder to advanced kidney disease. Whether patients had eGFR above 60 or below 30, semaglutide provided similar protection. One standout finding: patients with the most severe kidney damage (UACR ≥2000 mg/g) had the largest mortality reduction — 53% lower death risk (HR 0.47). The primary outcome included kidney failure (≥50% eGFR decline, eGFR <15, dialysis, transplant) and death from kidney or cardiovascular causes.","whyItMatters":"This analysis answers a crucial clinical question: does semaglutide help even the sickest kidney patients? The answer is yes. Advanced CKD patients — who have the fewest treatment options and worst outcomes — benefit as much or more than those with milder disease. This is practice-changing evidence that supports using semaglutide broadly across CKD severity stages, not just in early disease. The 53% mortality reduction in the most severely affected subgroup is particularly striking.","specificNumbers":"n=3,533 · Median follow-up 3.4 years · Primary outcome: HR 0.76 (0.66-0.88) · All-cause death: HR 0.80 (0.67-0.95) · Highest UACR subgroup death: HR 0.47 (0.31-0.70) · Mean eGFR 47 mL/min · Median UACR 568 mg/g · Consistent across all eGFR and UACR subgroups","methodology":"FLOW was a double-blind, randomized, placebo-controlled trial comparing once-weekly subcutaneous semaglutide 1 mg to placebo in people with type 2 diabetes and CKD. This analysis stratified participants by baseline kidney function (eGFR subgroups from <30 to ≥60) and albumin leak severity (UACR subgroups from <100 to ≥2000 mg/g). The primary outcome was a composite of major kidney events and kidney/cardiovascular death. Interaction tests assessed whether treatment effects differed across subgroups.","limitations":"This is a subgroup analysis of the main FLOW trial, so individual subgroups have fewer participants and wider confidence intervals. The trial enrolled only people with type 2 diabetes and CKD, so results may not apply to CKD from other causes. The median eGFR of 47 means the very lowest eGFR ranges (<30) had relatively fewer participants. The striking mortality result in the highest UACR subgroup (HR 0.47) should be interpreted cautiously given the subgroup interaction p-value of 0.02."},{"rthcId":"RPEP-16286","title":"Pharmacokinetic and pharmacodynamic results from a randomized controlled study with the growth hormone secretagogue receptor blocker PF-5190457 in recently abstinent patients with alcohol use disorder.","authors":"Tyler, Ryan E; Pfaff, Rabea K; Khan, Raja Muhammad Naseer; Loften, Anna; Zurick, Ryan; Zeng, Yi; Arisa, Oluwatobi T; Harvey, Charlotte; Akhlaghi, Fatemeh; Figg, William D; Farokhnia, Mehdi; Leggio, Lorenzo","year":2026,"journal":"The international journal of neuropsychopharmacology, 29(2)","doi":"10.1093/ijnp/pyaf081","pmid":"41474196","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16287","title":"Association of GLP-1 Receptor Agonist Prescriptions and Alcohol Consumption in the National Institutes of Health's All of Us Cohort.","authors":"Tyndall, Benjamin; Gasdaska, Angela; Brannock, M Daniel; Preble, Ed; McPheeters, Melissa; Marcial, Laura; Huda, Ariba; Egan, Josephine; Litwin, Tamara R; Adjemian, Jennifer; Sastry, Chandan; Farokhnia, Mehdi; Leggio, Lorenzo","year":2026,"journal":"medRxiv : the preprint server for health sciences","doi":"10.64898/2026.01.15.26344218","pmid":"41646707","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16288","title":"Gut Peptide Alterations in Type 2 Diabetes and Obesity: A Narrative Review.","authors":"Tzeravini, Evangelia; Simati, Stamatia; Anastasiou, Ioanna A; Dalamaga, Maria; Kokkinos, Alexander","year":2026,"journal":"Current obesity reports, 15(1), 8","doi":"10.1007/s13679-026-00687-7","pmid":"41575482","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16289","title":"Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of CRD-740, a PDE9 Inhibitor, in Chronic Heart Failure.","authors":"Udelson, James E; Bělohlávek, Jan; Dukát, Andrej; Ezekowitz, Justin; Goland, Sorel; Merkely, Bela; O'Meara, Eileen; Petrie, Mark C; Ponikowski, Piotr; Senni, Michele; Tokmakova, Mariya; Vardeny, Orly; Claggett, Brian; Moore, Elizabeth; Savard, Meghan; McKellar, Hillary; Surks, Howard K; Solomon, Scott D; McMurray, John J V","year":2026,"journal":"JACC. Heart failure, 14(1), 102706","doi":"10.1016/j.jchf.2025.102706","pmid":"41171251","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16290","title":"Improved quality of life with semaglutide in schizophrenia: Secondary analyses from a randomized controlled trial.","authors":"Uhrenholt, N; Ganeshalingam, A; Arnfred, S; Gæde, P; Pedersen, A K; Larsen, P V; Frystyk, J; Bilenberg, N","year":2026,"journal":"Schizophrenia research, 291, 20-26","doi":"10.1016/j.schres.2026.02.009","pmid":"41702353","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Semaglutide improved Physical Component Summary (PCS) scores at both weeks 15 and 30, with effect sizes exceeding the minimally important difference. Causal mediation analysis estimated that approximately half of the total PCS improvement at week 30 was mediated through weight change, though indirect effects did not reach statistical significance individually.\n\nNo significant effects were found for Mental Component Summary (MCS) scores or PANSS-6 psychiatric symptom scores. This suggests semaglutide's benefits in schizophrenia are primarily physical rather than psychological, at least over 30 weeks.","whyItMatters":"Antipsychotic-induced weight gain is one of the most burdensome side effects of schizophrenia treatment, contributing to metabolic disease and reduced quality of life. Showing that semaglutide — a GLP-1 peptide drug — can meaningfully improve physical quality of life in this vulnerable population provides evidence for its use beyond general obesity, addressing a significant unmet medical need.","specificNumbers":"","methodology":"Secondary analysis of a randomized, double-blind, placebo-controlled trial. 154 adults with schizophrenia spectrum disorder, prediabetes, and overweight/obesity were randomized 1:1 to once-weekly semaglutide or placebo for 30 weeks. Outcomes included SF-36v2 Physical and Mental Component Summary scores and PANSS-6 psychiatric symptoms. Causal mediation analyses estimated direct and indirect (via weight loss) effects at weeks 15 and 30.","limitations":"The 30-week duration may be too short to detect mental health quality of life improvements, which the authors acknowledge. The study enrolled only patients with prediabetes and overweight/obesity, so results may not apply to all schizophrenia patients. The mediation through weight loss, while estimated at ~50%, was not statistically significant, limiting causal conclusions. This was a secondary analysis of a trial designed with different primary endpoints."},{"rthcId":"RPEP-16291","title":"Real-world persistence and dose titration of GLP-1 receptor agonists in type 2 diabetes: A UK population-based cohort study by obesity and cardiovascular disease status.","authors":"Ulrich, Franziska S; Napoli, Nicola; Nielsen, Morten Frost; Burden, Andrea M","year":2026,"journal":"Diabetes, obesity & metabolism","doi":"10.1111/dom.70535","pmid":"41703773","tags":[],"studyType":"observational","evidenceStrength":"moderate","keyFinding":"Among 8,200 UK patients starting GLP-1 receptor agonists for type 2 diabetes, 41.1% discontinued within one year. Discontinuation was highest with oral semaglutide (55.8%), followed by subcutaneous semaglutide (46.4%), and lowest with dulaglutide (36.9%). Dose titration was frequently delayed — only 58% of semaglutide users reached recommended maintenance doses after 4 weeks, while 21% remained on starting doses.\n\nPatients without obesity were more likely to discontinue (49.2%) than those with BMI ≥30 (37–40%). By the 10th prescription, nearly half of subcutaneous semaglutide users were still on 0.5 mg rather than the 1 mg maintenance dose. Cardiovascular disease status did not significantly affect persistence patterns.","whyItMatters":"Clinical trials show GLP-1 drugs work well when taken as prescribed, but this real-world data reveals that 4 in 10 UK patients stop within a year and most don't reach optimal doses. This gap between trial efficacy and real-world effectiveness is critical for understanding actual patient outcomes and healthcare planning.","specificNumbers":"n=8,200 · 41.1% 1-year discontinuation · Dulaglutide 36.9% vs SC semaglutide 46.4% vs oral semaglutide 55.8% · Only 58% reached maintenance dose by week 4 · 21% stayed on starting dose","methodology":"Population-based retrospective cohort study using UK primary care data (IQVIA Medical Research Data/THIN database). Identified 8,200 adults with type 2 diabetes who started GLP-1 RAs between March 2018 and June 2023 with at least 1 year of follow-up. Discontinuation risk was estimated using the Aalen-Johansen estimator; Cox models assessed associations with patient characteristics. Dosing trajectories were tracked across individual prescriptions.","limitations":"Observational design cannot determine why patients discontinued — whether due to side effects, cost, lack of efficacy, or other reasons. UK prescribing practices may not generalize to other countries. The study period largely predates the obesity indication for semaglutide, so persistence patterns may be changing. Tirzepatide was not included as it was not yet widely available in the UK during the study period."},{"rthcId":"RPEP-16292","title":"Real-world treatment trajectories preceding GLP-1 receptor agonist initiation in type 2 diabetes: A descriptive UK population-based cohort study on adherence to national clinical guidelines.","authors":"Ulrich, Franziska S; Frost Nielsen, Morten; Napoli, Nicola; Burden, Andrea M","year":2026,"journal":"Diabetes, obesity & metabolism","doi":"10.1111/dom.70548","pmid":"41741822","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16293","title":"Peptide-nanoparticle platforms for antisense therapeutics: A coarse-grained modeling approach to brain delivery.","authors":"Uner, Burcu Yesildag; Demir, Alper; Zhou, Pingkun; Taskiran, Ekim Z; Wassenaar, Tsjerk","year":2026,"journal":"Computers in biology and medicine, 203, 111479","doi":"10.1016/j.compbiomed.2026.111479","pmid":"41581469","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Using AI-driven proteomics and RNA sequence integration, the researchers mapped disrupted gene circuits following TBI and identified specific therapeutic targets including redox-sensitive mitochondrial regulators and neuroimmune interface genes. They then designed peptide-nanoparticle formulations in silico that incorporate targeting ligands for disrupted circuits and redox-sensitive release mechanisms. The platform demonstrates a closed-loop, data-guided strategy integrating AI-based gene network profiling with rational nanocarrier design, validated computationally through coarse-grained molecular simulations.","whyItMatters":"Traumatic brain injury affects millions worldwide, and current treatments remain inadequate because the damage involves multiple interconnected biological pathways. This study's approach — using AI to find the right targets and then designing peptide nanoparticles to reach them — represents a new precision medicine framework that could lead to more effective TBI treatments and be applied to other complex brain disorders.","specificNumbers":"","methodology":"The researchers used AI-driven proteomics and RNA sequence integration to map altered signaling pathways in rodent TBI models. They employed computational predictions to identify gene-circuit nodes susceptible to therapeutic intervention, then designed nanoparticle formulations optimized through in silico coarse-grained molecular modeling. The nanocarriers incorporated peptide-based targeting ligands and redox-sensitive release mechanisms.","limitations":"This is entirely a computational study — the nanoparticle designs were optimized in silico but have not been tested in living organisms. The gene circuit analysis is based on rodent TBI models, and while the authors note pathway conservation with humans, direct human validation is needed. Coarse-grained modeling simplifies molecular interactions, which may not fully predict real-world behavior."},{"rthcId":"RPEP-16294","title":"Micronutrient and Nutritional Deficiencies Associated With GLP-1 Receptor Agonist Therapy: A Narrative Review.","authors":"Urbina, Jorge; Salinas-Ruiz, Luis Eduardo; Valenciano, César; Clapp, Benjamin","year":2026,"journal":"Clinical obesity, 16(1), e70070","doi":"10.1111/cob.70070","pmid":"41549912","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16295","title":"Ethosomal Nanocarriers for Hydrophilic Peptide Encapsulation: Formulation Optimization, Stability, and In Vitro Release Performance.","authors":"Uzuner, Yasemin Yağan; Sevinç, Hakan; Kanlidere, Zeynep","year":2026,"journal":"Molecules (Basel, Switzerland), 31(4)","doi":"10.3390/molecules31040744","pmid":"41752521","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16296","title":"Analysis of growth hormone releasing hormone and its analogs in urine using nano liquid chromatography coupled with quadrupole/orbitrap mass spectrometry.","authors":"Uçaktürk, Ebru; Nemutlu, Emirhan","year":2026,"journal":"Journal of pharmaceutical and biomedical analysis, 268, 117207","doi":"10.1016/j.jpba.2025.117207","pmid":"41138283","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16297","title":"Income disparities and accessibility to Semaglutide: implications for diabetes management and policy reform.","authors":"Vaidya, Varun; Estep, Sophia; Gupte, Renuka","year":2026,"journal":"International journal for quality in health care : journal of the International Society for Quality in Health Care, 38(1)","doi":"10.1093/intqhc/mzaf131","pmid":"41437637","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16298","title":"Advances in the Pharmacological Treatment of Heart Failure With Preserved Ejection Fraction.","authors":"Valente, Valeria; Beer, Benedikt N; Savarese, Gianluigi","year":2026,"journal":"International journal of heart failure, 8(1), 24-42","doi":"10.36628/ijhf.2025.0111","pmid":"41696054","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16299","title":"Airway Management in the Age of GLP-1 Receptor Agonists: New Challenges and Solutions.","authors":"Valkeniers, Karolien; Wallyn, An; Van de Putte, Peter; Hogg, Rosemary M G","year":2026,"journal":"Anesthesiology clinics, 44(1), 125-137","doi":"10.1016/j.anclin.2025.10.010","pmid":"41781102","tags":["glp-1","safety"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"GLP-1 receptor agonists slow gastric emptying as part of their mechanism of action, which creates a new challenge for anesthesiologists: patients on these drugs may have food or liquid remaining in their stomachs even after standard fasting periods before surgery. This residual gastric content increases the risk of regurgitation and pulmonary aspiration during anesthesia — a potentially life-threatening complication.\n\nThe risk is particularly elevated for patients who already have gastroparesis (delayed stomach emptying) or who are undergoing procedures without a protected airway (such as sedation without intubation). The article reviews international consensus guidelines and provides structured recommendations for perioperative risk stratification and management of patients on GLP-1 drugs.","whyItMatters":"With tens of millions of people now taking GLP-1 drugs for diabetes and weight loss, anesthesiologists are encountering this issue daily. Standard fasting guidelines (nothing to eat for 6-8 hours before surgery) were developed before GLP-1 drugs existed and may not be adequate for these patients. This review addresses a genuine patient safety concern and provides practical guidance for one of the most common drug-anesthesia interactions clinicians now face.","specificNumbers":"GLP-1 RAs increase residual gastric content · Standard fasting may be inadequate · Multiple international guidelines reviewed · Risk stratification framework provided","methodology":"This is a narrative review published in Anesthesiology Clinics that summarizes current evidence on GLP-1 receptor agonists' effects on gastric emptying and their implications for anesthesia and airway management. The authors reviewed various international consensus guidelines and synthesized recommendations for perioperative management, including risk stratification approaches for patients on GLP-1 drugs.","limitations":"The evidence base for specific perioperative management of GLP-1 RA patients is still emerging, and most guidelines are based on expert consensus rather than large randomized trials. The actual incidence of aspiration events attributable to GLP-1 drugs during anesthesia is not well quantified. Recommendations may evolve as more data becomes available. The review does not specify how different GLP-1 drugs (short-acting vs. long-acting) compare in aspiration risk."},{"rthcId":"RPEP-16300","title":"Med14 phosphorylation shapes genomic response to GLP-1 agonists.","authors":"Van de Velde, Sam; Yu, Jungting; Garrett Evensen, K; Pakhlevanyan, Edmund; Williams, April E; Shaw, Reuben J; Montminy, Marc","year":2026,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 123(10), e2536772123","doi":"10.1073/pnas.2536772123","pmid":"41779793","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16301","title":"Characterisation of real-world patients who discontinued a glucagon-like peptide-1 agonist.","authors":"Van Laren, Jessica; Friesleben, Cari; Gershovich, Olga; Helm, Lindsey; Patel, Rachana J; Delate, Thomas","year":2026,"journal":"Diabetes, obesity & metabolism","doi":"10.1111/dom.70579","pmid":"41713959","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16302","title":"Efficacy of Dual Glucagon and GLP-1 Agonists as New Treatments for Type II Diabetes.","authors":"Vats, Jatin; Chauhan, Ajesh; Rajput, Shivam; Sridhar, Sathvik Belagodu; Vashist, Chetan; Mittal, Arun; Malviya, Rishabha","year":2026,"journal":"Mini reviews in medicinal chemistry","doi":"10.2174/0113895575419389251118100027","pmid":"41735212","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16303","title":"Human fetal circulating factors from pregnancies complicated by obesity upregulate genes associated with pathological hypertrophy in neonatal rat cardiomyocytes.","authors":"Vaughan, Owen R; Goodspeed, Andrew; Sucharov, Carmen C; Powell, Theresa L; Jansson, Thomas","year":2026,"journal":"American journal of physiology. Heart and circulatory physiology, 330(1), H124-H136","doi":"10.1152/ajpheart.00375.2025","pmid":"41269698","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16304","title":"ATP-sensitive peptide-based coacervates for intracellular delivery of therapeutic oligonucleotides.","authors":"Vedekhina, Tatiana; Anufriev, Vladislav; Polischuk, Nicole; Malakhova, Elizaveta; Alieva, Sabina; Severov, Viacheslav; Bogomiakova, Margarita; Bobrovsky, Pavel; Varizhuk, Anna","year":2026,"journal":"Frontiers in molecular biosciences, 13, 1767656","doi":"10.3389/fmolb.2026.1767656","pmid":"41767047","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16305","title":"Innovative Diabetes Therapies and Impact on Peripheral and Autonomic Diabetic Neuropathies: A State-of-the-Art Review.","authors":"Vekic, Jelena; Zeljkovic, Aleksandra; Maggio, Viviana; Rizzo, Manfredi; Medenica, Sanja","year":2026,"journal":"Diabetes therapy : research, treatment and education of diabetes and related disorders","doi":"10.1007/s13300-025-01828-2","pmid":"41493731","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16306","title":"Patients after acute myocardial infarction: potential of semaglutide in prognosis for reducing events and mortality.","authors":"Velasco, Á; Pascual Ramos, I; Rodríguez Alonso, P; Denche Sanz, C; Tello, R; Solís, J","year":2026,"journal":"Revista clinica espanola, 226(2), 502455","doi":"10.1016/j.rceng.2026.502455","pmid":"41520703","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16307","title":"Reviewing the Artificial Intelligence Boost for Accelerating the Development of Novel Antimicrobial Peptides.","authors":"Velásquez-Mejía, Lorena; Vidal-Limon, Abraham; Flores-Vargas, Gabriela; Ruiz-May, Eliel; Scavone, Paola; de la Fuente-Nunez, Cesar; Zamora-Briseño, Jesús Alejandro","year":2026,"journal":"Journal of applied microbiology","doi":"10.1093/jambio/lxag036","pmid":"41614958","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16308","title":"Impact of GLP-1 Receptor Agonist Therapy on Atrial Fibrillation Recurrence After Catheter Ablation in Obese Patients: A Real-World Data Analysis.","authors":"Venier, Sandrine; Defaye, Pascal; Lochon, Lisa; Benali, Rémi; Bisson, Arnaud; Carabelli, Adrien; Diouf, Youssou; Jacon, Peggy; Fauchier, Laurent","year":2026,"journal":"Circulation. Arrhythmia and electrophysiology, 19(1), e014101","doi":"10.1161/CIRCEP.125.014101","pmid":"41446932","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 6,700 propensity-matched obese patients (matched on 82 variables), GLP-1RA users had significantly lower AF recurrence after ablation: 6.66% vs. 7.72% (HR 0.82, 95% CI 0.76–0.88, p=0.01). All-cause mortality was 27% lower (HR 0.73, 95% CI 0.59–0.91, p=0.01). Heart failure hospitalization was 20% lower (HR 0.80, 95% CI 0.71–0.90, p=0.001). There was no significant difference in need for repeat ablation procedures. These benefits were observed over a median 2-year follow-up (IQR 0.8–3.2 years).","whyItMatters":"AF recurrence after ablation is a major clinical problem, affecting 20-40% of patients within the first year. Obesity is a key risk factor for recurrence, and no medication has been proven to consistently reduce AF recurrence post-ablation. If GLP-1 drugs can reduce AF recurrence — potentially by addressing the obesity-related atrial substrate changes, inflammation, and autonomic dysfunction that drive the arrhythmia — they could become a standard adjunctive therapy for obese patients undergoing AF ablation.","specificNumbers":"","methodology":"Retrospective cohort study using the TriNetX research network (>100 million patient records). Included adult obese patients (BMI >30) who underwent AF ablation between January 2015 and January 2025. Cohorts were divided into GLP-1RA users (n=3,350) and non-users (n=3,350), with 1:1 propensity score matching across 82 clinical and demographic variables including age, sex, race, AF subtype, cardiovascular comorbidities, and medications.","limitations":"This is a retrospective observational study, so it cannot prove causation. Despite matching on 82 variables, residual confounding is possible — GLP-1RA users may differ from non-users in unmeasured ways. The TriNetX database relies on electronic health records, which may have coding inaccuracies for AF recurrence detection. The study could not determine which specific GLP-1 drugs were used or at what doses. The absolute difference in AF recurrence (6.66% vs. 7.72%) is relatively small, though the mortality and hospitalization reductions are more clinically significant."},{"rthcId":"RPEP-16309","title":"Pre-stroke weight loss by glucagon-like peptide 1 receptor and neuropeptide Y receptor Y2 activation improves post-stroke functional recovery in male diabetic mouse models.","authors":"Vercalsteren, Ellen; Karampatsi, Dimitra; Neicu, Maria; Romanitan, Mihaela Oana; Haebel, Peter; Bleymehl, Katherin; Nyström, Thomas; Klein, Thomas; Darsalia, Vladimer; Patrone, Cesare","year":2026,"journal":"Diabetologia, 69(1), 230-243","doi":"10.1007/s00125-025-06567-4","pmid":"41094027","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Pre-stroke weight loss achieved through GLP-1R activation with semaglutide, and more potently through dual co-activation of GLP-1 and NPY2 receptors, improved post-stroke functional recovery in diabetic mice. This recovery effect was independent of glycemic regulation — it occurred upstream of blood sugar control, driven by weight loss itself.\n\nPost-stroke recovery in type 2 diabetic mice was inversely associated with peripheral IGF-1 levels. Additionally, when semaglutide and/or BI8271 were administered acutely (1 and 24 hours after reperfusion), they provided direct neuroprotection — improving grip strength, reducing stroke volume, and increasing surviving neuron counts — independently of their metabolic effects.\n\nA diet-switching control group that achieved the same weight loss range confirmed that pharmacological weight loss provided benefits beyond what simple caloric restriction offered.","whyItMatters":"The dual epidemics of diabetes and obesity are driving increased stroke incidence worldwide. Type 2 diabetes worsens stroke outcomes, yet no specific treatments exist for this. This study reveals that GLP-1 drugs like semaglutide — already widely prescribed for diabetes and obesity — could offer a preventive strategy by both reducing pre-stroke weight and providing acute neuroprotection when stroke occurs. The addition of NPY2R agonism as a potentiator is a novel therapeutic concept.","specificNumbers":"","methodology":"C57BL/6J mice were fed a high-fat diet for 5 months to induce obesity, hyperglycemia, and insulin resistance (type 2 diabetes features). Weight loss was induced over 4 weeks with semaglutide and/or BI8271. A diet-switch control group achieved equivalent weight loss via standard diet. Stroke was induced by transient middle cerebral artery occlusion (tMCAO). Primary outcomes included grip strength recovery and lateralized sensorimotor integration. Secondary outcomes included stroke volume and serum IGF-1 levels. In additional acute studies, drugs were given 1 and 24 hours post-reperfusion, with assessment of stroke volume and NeuN-positive surviving neurons.","limitations":"This was a mouse study (male C57BL/6J only), and type 2 diabetes was diet-induced rather than spontaneous, which may not fully replicate human disease. Only male mice were studied, limiting generalizability. The tMCAO stroke model, while standard, does not capture all types of human stroke. BI8271 (NPY2R agonist) is not an approved drug, so the dual-agonist approach is further from clinical translation than semaglutide alone. Specific quantitative recovery data were not detailed in the abstract."},{"rthcId":"RPEP-16310","title":"Deciphering the molecular roles of antimicrobial peptides in plant innate immunity and their potential applications in crop protection.","authors":"Verma, Rohini; Yadav, Shivam; Likhita, Jonnada; Kumar, Sumit; Shelke, Manisha; Pal, Riti; Prajapati, Manoj Kumar; Behera, Prateek Ranjan; Singh, Yashowardhan; Puyam, Anita; Chenari Bouket, Ali; Alenezi, Faizah N; Kumar, Anil; Meena, Mukesh","year":2026,"journal":"Plant physiology and biochemistry : PPB, 230, 110961","doi":"10.1016/j.plaphy.2025.110961","pmid":"41422562","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16311","title":"Guideline-Directed Medical Therapy for Diabetic Kidney Disease: Advances in Primary and Secondary Prevention.","authors":"Verma, Sidhant; Katwal, Susant; Akula, Harshika Reddy; Inamdar, Alfiya; Kundukulam, Sarah S; Khan, Mariyam; Satti, Ahmad Bin Abdul Qayyum; Menon, Shweta; Rai, Manju","year":2026,"journal":"Cureus, 18(1), e101867","doi":"10.7759/cureus.101867","pmid":"41717165","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16312","title":"CagriSema Reduces Blood Pressure in Adults With Overweight or Obesity: REDEFINE 1.","authors":"Verma, Subodh; Böttcher, Morten; Brown, Paul; Dicker, Dror; Rubino, Domenica; Sbraccia, Paolo; Sharma, Arya M; Smedegaard, Lærke; Sørrig, Rasmus; Garvey, W Timothy","year":2026,"journal":"Hypertension (Dallas, Tex. : 1979), 83(2), e26055","doi":"10.1161/HYPERTENSIONAHA.125.26055","pmid":"41328546","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In the phase 3a REDEFINE 1 trial (n=3,417; 68 weeks), CagriSema 2.4 mg/2.4 mg vs. placebo showed:\n\n- Systolic BP change: -10.9 vs. -2.8 mmHg\n- Diastolic BP change: -5.4 vs. -1.7 mmHg\n- BP target achievement at week 68: 63.0% vs. 32.0%\n- Among resistant hypertension patients (n=167): 42.0% vs. 29.3% reached BP targets (OR 1.7; 95% CI 0.7-4.4)\n- 39.6% of CagriSema patients on antihypertensive medications decreased or stopped treatment vs. 18.8% with placebo\n\nThe blood pressure reductions were clinically relevant across a wide range of subgroups including those stratified by baseline BMI, hypertension status, and resistant hypertension.","whyItMatters":"Obesity and hypertension frequently co-exist and compound cardiovascular risk. A treatment that addresses both simultaneously — reducing weight and blood pressure — could significantly reduce the need for multiple medications. The finding that 40% of patients could reduce or stop their blood pressure drugs is particularly meaningful for simplifying treatment and improving adherence.","specificNumbers":"","methodology":"Secondary and post hoc analyses of the REDEFINE 1 trial (NCT05567796), a phase 3a, 68-week, randomized, double-blind trial. Adults without diabetes with BMI ≥30 (or ≥27 with obesity-related complication) were randomized to CagriSema 2.4/2.4 mg (n=2,108), semaglutide 2.4 mg (n=302), cagrilintide 2.4 mg (n=302), or placebo (n=705), plus lifestyle intervention. Blood pressure changes were analyzed by subgroup including baseline hypertension status and medication use.","limitations":"Blood pressure analysis was secondary/post hoc, not a pre-specified primary endpoint. The resistant hypertension subgroup was small (n=167) with wide confidence intervals. The trial excluded people with diabetes, limiting generalizability to the T2D population. Whether blood pressure benefits are directly from the drug or mediated entirely through weight loss was not fully resolved."},{"rthcId":"RPEP-16313","title":"Effects of Glucagon-Like Peptide-1 Receptor Agonists (Mono and Combination Therapy) on Energy Expenditure: A Scoping Review.","authors":"Vieira, Flavio T; Deng, ZhiDi; Muller, Manfred J; Bergamasco, Giovanna G L; Cawsey, Sarah; Manco, Melania; Heymsfield, Steven B; Prado, Carla M; Haqq, Andrea M","year":2026,"journal":"Obesity reviews : an official journal of the International Association for the Study of Obesity, e70116","doi":"10.1111/obr.70116","pmid":"41782395","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16314","title":"Maintaining microbiota across diverse symbiotic organs in Euprymna scolopes: Insights into shared immune responses.","authors":"Vijayan, Nidhi; Briseño, John; Simakov, Oleg; Nyholm, Spencer V","year":2026,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 123(1), e2512903122","doi":"10.1073/pnas.2512903122","pmid":"41428895","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16315","title":"Vestibular migraine. Clinical and diagnostic challenges, and emerging therapeutic approaches.","authors":"Villar-Martinez, Maria Dolores; Abdalla, Ahmed; Goadsby, Peter J","year":2026,"journal":"Current opinion in neurology, 39(1), 42-47","doi":"10.1097/WCO.0000000000001447","pmid":"41324222","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16316","title":"Cardiovascular benefits of obesity therapies: an overview of obesity medicines and metabolic bariatric surgery.","authors":"Villelabeitia, Itxaso K; Cohen, Ricardo; le Roux, Carel W","year":2026,"journal":"Heart (British Cardiac Society)","doi":"10.1136/heartjnl-2025-326812","pmid":"41730547","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16317","title":"Assessment of thyroid cancer risk associated with glucagon-like peptide 1 receptor agonist use.","authors":"Vilsbøll, Tina; Stellfeld, Michael; Aroda, Vanita R; Dandanell, Sune; David, Jens-Peter; Kristiansen, Ceyda T P; Rasmussen, Søren; Roberts, Fiona L; Hegedüs, Laszlo","year":2026,"journal":"Diabetes, obesity & metabolism, 28(2), 1499-1507","doi":"10.1111/dom.70291","pmid":"41287564","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16318","title":"C-peptide in Precision Diabetes Care and Beyond: A Comprehensive Review.","authors":"Vinay, Eligar Somashekar; Laxmi Narsimha Rao, Bondugulapati; Saf, Naqvi; Gautam, Das","year":2026,"journal":"Clinical medicine insights. Endocrinology and diabetes, 19, 11795514251397811","doi":"10.1177/11795514251397811","pmid":"41694179","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16319","title":"Comparison of oral versus intravenous glucose exposure on plasma growth hormone levels: a crossover study in healthy volunteers.","authors":"Vinten, Anna Katarina; Jørgensen, Nanna Thurmann; Budtz-Jørgensen, Esben; Klose, Marianne; Andreassen, Mikkel","year":2026,"journal":"Pituitary, 29(1), 28","doi":"10.1007/s11102-025-01633-x","pmid":"41524818","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16320","title":"Computational examination of magainin-I-KL mediated disruption of E. coli biofilms via CsgA amyloid interference.","authors":"Vinutha, A S; Akshay, S; Sree Agash, S G; Chandrasekhar, G; Bhattacharya, Asmita; Rajasekaran, R","year":2026,"journal":"Archives of microbiology, 208(5)","doi":"10.1007/s00203-026-04797-7","pmid":"41724836","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16321","title":"Weight Loss Medications for Adult Patients With Obesity and Binge Eating-A Systematic Review and Meta-analysis.","authors":"Violante-Cumpa, Jorge Rafael; Rios-Ortega, Adriana Gabriela; Sánchez-García, Adriana; Treviño-Alvarez, Andres Marcelo; González-Cruz, Daniela Cecilia; Manzanares-Gallegos, Dulce Maria; Gutiérrez-Dávila, Luis Fernando; Moreno-Alvarado, Marcela; Montelongo-Cepeda, Jose Emiliano; de Las Fuentes-Cepeda, Alejandra; Santos-Santillana, Annete A; Guzman-Cisneros, Daniel; González-González, Jose Gerardo; Mancillas-Adame, Leonardo G; Rodríguez-Gutiérrez, René","year":2026,"journal":"Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists","doi":"10.1016/j.eprac.2025.11.002","pmid":"41513086","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16322","title":"Peptide receptor radionuclide therapy in neuroendocrine tumours: advances, combination strategies, and future directions.","authors":"Virgolini, Irene J; Di Santo, Gianpaolo; Santo, Giulia","year":2026,"journal":"European journal of nuclear medicine and molecular imaging","doi":"10.1007/s00259-025-07750-w","pmid":"41689648","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16323","title":"Toxicity of Semaglutide upon sub chronic administration in Rabbits.","authors":"Vishwanath, Chandrashekara; Krishnachari, Kumar; Adiga, Gowrav Perdur; Madhavdeshmukh, Manohar; Das, Akanksh; Alandur Jamal, Zabiullah; Bhoite, Prabhakar; Ponnusamy, Kalaiselvan; Krishnappa, Mohan; Ahuja, Varun; Pananchukunnath, Manoj Kumar; Kunhihitlu, Anil; Jain, Vikas","year":2026,"journal":"Toxicological research, 42(1), 1-17","doi":"10.1007/s43188-025-00308-w","pmid":"41503438","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16324","title":"Gastric ultrasound in patients receiving semaglutide: a prospective, multicentre, matched control study.","authors":"Vlaeminck, Nils; Van de Putte, Peter; Dekeyser, Melanie; Baert, Nele; Wallyn, An; Vernieuwe, Lynn; Smitz, Carine; Wouters, Kristien; Van Cauwenberghe, Jolijn; Saldien, Vera","year":2026,"journal":"Anaesthesia","doi":"10.1111/anae.70129","pmid":"41631344","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16325","title":"GLP-1, Pancreatic β-Cells, and Insulin Secretion: What We Know and Where We Need to Go.","authors":"Vogt, Éverton L; Kowaltowski, Alicia J","year":2026,"journal":"Diabetes, 75(3), 403-413","doi":"10.2337/db25-0695","pmid":"41525103","tags":["glp-1"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"This review argues that GLP-1 receptor agonists should be understood as integrative regulators of pancreatic beta-cell function, not just appetite suppressors. The authors detail how GLP-1 modulates multiple intracellular mediators — calcium, glutamate, GABA, serotonin, and urocortin-3 — each with complex and sometimes contradictory roles in triggering insulin release.\n\nThe review highlights emerging evidence that GLP-1 analogs also affect mitochondrial shape and the cell's oxidative balance. Because beta-cells have relatively low levels of antioxidant enzymes and depend heavily on both glycolytic and mitochondrial metabolism to produce insulin, GLP-1's influence on mitochondrial dynamics and reactive oxygen species may be central to keeping these cells functional and alive.\n\nThe authors identify three mechanistic dimensions — intracellular neurotransmitters, mitochondrial remodeling, and redox control — as the most promising areas for advancing understanding of how GLP-1 works at the cellular level.","whyItMatters":"GLP-1 drugs like semaglutide and tirzepatide are among the most prescribed medications in the world for diabetes and obesity, yet scientists still don't fully understand how they affect the insulin-producing cells of the pancreas. This review maps out what's known and — critically — what's still unknown, pointing researchers toward the specific gaps that could lead to better, more targeted therapies. Understanding these mechanisms could help design next-generation drugs that protect beta-cells more effectively.","specificNumbers":"Three key mechanistic dimensions identified · Multiple intracellular mediators (Ca²⁺, glutamate, GABA, serotonin, urocortin-3) · Low antioxidant enzyme expression in β-cells","methodology":"This is a narrative review synthesizing current literature on GLP-1 receptor agonist effects on pancreatic beta-cell signaling. The authors reviewed published studies on intracellular mediators, calcium/cAMP interplay, mitochondrial dynamics, and redox homeostasis in beta-cells, then identified knowledge gaps and proposed priority research directions.","limitations":"As a narrative review rather than a systematic review, the paper reflects the authors' interpretation and selection of evidence rather than a comprehensive, unbiased survey. No new experimental data were generated. Some of the proposed mechanisms (particularly around mitochondrial remodeling and redox control) are based on emerging or limited evidence that hasn't been fully replicated."},{"rthcId":"RPEP-16326","title":"Fine-Tuning of the Neuropeptide Y1 G Protein-Coupled Receptor by the Tryptophan6.48 \"Toggle Switch\".","authors":"Voitel, Matthias; Pankonin, Maik; Vogel, Alexander; Leitner, Karl; Kaiser, Anette; Huster, Daniel; Hildebrand, Peter W; Smith, Albert A","year":2026,"journal":"Journal of the American Chemical Society, 148(1), 194-205","doi":"10.1021/jacs.5c07143","pmid":"41414765","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16327","title":"PROTEIMERs as catalytic inhibitors of APP mRNA translation: Toward a new therapeutic for Alzheimer's disease.","authors":"von Salzen, Daniel; Senn, Katherine; Cho, Hannah K; Cahill, Catherine M; Rogers, Jack T; Cho, HyunDae D","year":2026,"journal":"Journal of Alzheimer's disease : JAD, 109(1), 303-314","doi":"10.1177/13872877251393907","pmid":"41259272","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16328","title":"A Systematic Review on GLP-1 Receptor Agonists in Reproductive Health: Integrating IVF Data, Ovarian Physiology and Molecular Mechanisms.","authors":"Voros, Charalampos; Chatzinikolaou, Fotios; Papapanagiotou, Ioannis; Polykalas, Spyridon; Mavrogianni, Despoina; Koulakmanidis, Aristotelis-Marios; Athanasiou, Diamantis; Kanaka, Vasiliki; Bananis, Kyriakos; Athanasiou, Antonia; Athanasiou, Aikaterini; Papadimas, Georgios; Tsimpoukelis, Charalampos; Vaitsis, Dimitrios; Karpouzos, Athanasios; Daskalaki, Maria Anastasia; Kanakas, Nikolaos; Theodora, Marianna; Thomakos, Nikolaos; Antsaklis, Panagiotis; Loutradis, Dimitrios; Daskalakis, Georgios","year":2026,"journal":"International journal of molecular sciences, 27(2)","doi":"10.3390/ijms27020759","pmid":"41596408","tags":["glp-1","reproductive-health","pcos"],"studyType":"systematic-review","evidenceStrength":"moderate","keyFinding":"GLP-1 receptor agonists directly affect ovarian biology — not just through weight loss, but by acting on ovarian cells themselves. In women with PCOS, these drugs improved menstrual regularity, reduced free testosterone, and increased sex hormone-binding globulin. Liraglutide combined with metformin significantly improved IVF pregnancy rates, while exenatide increased natural conception rates. At the molecular level, GLP-1 receptor activation promotes granulosa cell growth through FOXO1 signaling and modifies steroid hormone production by suppressing key steroidogenic enzymes. However, animal studies raised concerns about potential ovarian and uterine damage at certain doses, including oxidative stress, granulosa cell death, and uterine inflammation.","whyItMatters":"Millions of women of reproductive age now take GLP-1 drugs, and many have PCOS — a condition where these drugs are increasingly used. This review reveals that GLP-1 drugs do far more than just help with weight loss; they directly influence ovarian function, hormone production, and fertility at the cellular level. The finding that liraglutide improved IVF success rates is clinically significant, but the animal data showing potential ovarian damage raises important safety questions that need answers.","specificNumbers":"","methodology":"Systematic review following PRISMA guidelines, searching PubMed, Scopus, and Web of Science for randomized trials, prospective studies, animal models, and cellular experiments evaluating GLP-1 receptor agonist effects on reproductive or ovarian outcomes. Data included metabolic changes, androgen levels, menstrual regularity, ovarian structure, granulosa cell biology, signaling pathways, and fertility/IVF outcomes.","limitations":"Most clinical evidence comes from women with PCOS, so findings may not apply to women without PCOS. Animal studies showed contradictory results (both beneficial and harmful), suggesting dose and context matter significantly. The review acknowledges limited understanding of the molecular mechanisms and calls for controlled human research to clarify reproductive safety, particularly in non-PCOS populations and IVF settings."},{"rthcId":"RPEP-16329","title":"Evaluation of cultivation performance of S. cerevisiae strains expressing GLP-1-GIP peptide precursors.","authors":"Voulgaris, Ioannis; Nielsen, Anders Nygaard; Petersen, Tine; Brandt, Jakob; Jensen, Sanne","year":2026,"journal":"Biotechnology letters, 48(1), 33","doi":"10.1007/s10529-026-03704-w","pmid":"41642357","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16330","title":"Factors Associated with GLP-1 Receptor Agonist Use in Patients with Type 2 Diabetes and Established Atherosclerotic Cardiovascular Disease: A Retrospective Propensity-Score Matched Analysis.","authors":"Vournas, Georgios; Mourgos, Leonidas; Doumas, Michael; Liberopoulos, Evangelos N; Kotsa, Kalliopi; Koufakis, Theocharis","year":2026,"journal":"Diseases (Basel, Switzerland), 14(2)","doi":"10.3390/diseases14020075","pmid":"41745113","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16331","title":"GLP1 receptor analogues and perioperative management considerations: A narrative review.","authors":"Vázquez Lima, A; Vidal Lopo, M","year":2026,"journal":"Revista espanola de anestesiologia y reanimacion, 73(1), 501985","doi":"10.1016/j.redare.2026.501985","pmid":"41539425","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16332","title":"Psychiatric Safety of Tirzepatide in People With Obesity and No Known Major Psychopathology: A Post Hoc Analysis of SURMOUNT.","authors":"Wadden, Thomas A; Oquendo, Maria A; Kushner, Robert F; Cao, Dachuang; Karanikas, Chrisanthi A; Kechter, Afton; Murphy, Madhumita A","year":2026,"journal":"Obesity (Silver Spring, Md.), 34(3), 565-578","doi":"10.1002/oby.70122","pmid":"41537305","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In 4,056 adults with obesity and no known major psychopathology from the SURMOUNT trials, tirzepatide was not associated with increased depression risk compared to placebo. At week 72, tirzepatide-treated participants had significantly lower PHQ-9 depression scores (1.9 vs. 2.4; treatment difference -0.6; p < 0.001) and were less likely to shift to a more severe depression category (18.2% vs. 24.3%; p < 0.001). Suicidal ideation was reported by 0.6% in both groups, and suicidal behavior (nonfatal) occurred in 0.1% on tirzepatide vs. 0% on placebo. Psychiatric adverse events were similar between groups.","whyItMatters":"With tirzepatide rapidly becoming one of the most widely prescribed weight loss drugs worldwide, understanding its psychiatric safety profile is critical. Regulatory agencies and the public have raised concerns about potential links between incretin-based therapies and depression or suicidality. This large-scale analysis from three pivotal trials provides reassuring evidence that tirzepatide does not increase depression risk — and may even slightly improve depressive symptoms — in people without pre-existing psychiatric conditions.","specificNumbers":"","methodology":"Post hoc analysis pooling data from three SURMOUNT clinical trials (SURMOUNT-1, -2, -3). Participants (N = 4,056) with overweight/obesity and no known major psychopathology received tirzepatide (5/10/15 mg or maximum tolerated dose) or placebo. Depression was measured using the Patient Health Questionnaire-9 (PHQ-9) and suicidal ideation/behavior using the Columbia-Suicide Severity Rating Scale (C-SSRS) over 72 weeks. Adverse events related to nervous system and psychiatric disorders were also collected.","limitations":"This is a post hoc analysis, not a prospectively designed psychiatric safety study. Participants with known major psychopathology were excluded from the SURMOUNT trials, so results cannot be generalized to people with depression, bipolar disorder, or other psychiatric conditions. The 0.1% suicidal behavior rate in the tirzepatide group (vs. 0% placebo) is based on very small numbers and cannot be conclusively interpreted. Follow-up was limited to 72 weeks."},{"rthcId":"RPEP-16333","title":"Disparities in diabetes treatment and monitoring for people with and without mental disorders: a systematic review and meta-analysis.","authors":"Wagner, Elias; Højlund, Mikkel; Fiedorowicz, Jess G; Nielsen, René Ernst; Østergaard, Søren Dinesen; Høye, Anne; Heiberg, Ina H; Poddighe, Laura; Delogu, Marco; Holt, Richard I G; Correll, Christoph U; Cortese, Samuele; Carvalho, Andre F; Boyer, Laurent; Dragioti, Elena; Du Rietz, Ebba; Firth, Joseph; Fusar-Poli, Paolo; Hartman, Catharina A; Larsson, Henrik; De Giorgi, Riccardo; Lehto, Kelli; Lindgren, Peter; Manchia, Mirko; Nordentoft, Merete; Skonieczna-Żydecka, Karolina; Veroniki, Areti-Angeliki; Marx, Wolfgang; Campana, Mattia; Mortazavi, Matin; Hasan, Alkomiet; Stubbs, Brendon; Taipale, Heidi; Vancampfort, Davy; Vieta, Eduard; Solmi, Marco","year":2026,"journal":"The lancet. Psychiatry, 13(2), 112-124","doi":"10.1016/S2215-0366(25)00332-3","pmid":"41506273","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16334","title":"Patients on Long-Term Preoperative Glucagon-Like Peptide-1 Receptor Agonist Therapy Show Significant Reductions in Postoperative Complications After Elective Laminectomy in Overweight Adults: A Propensity-Matched Study.","authors":"Wahid, Muaz; Zaidi, Zuhair; Isa, Salman; Alshaikhsalama, Yousef; Aoun, Salah G","year":2026,"journal":"International journal of spine surgery","doi":"10.14444/8856","pmid":"41672939","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16335","title":"Reassessing cancer risk with GLP-1 receptor agonists: a comprehensive meta-analysis of gastrointestinal malignancies.","authors":"Wali, Adil Farooq; Rangraze, Imran; Khan, Shehla; Mufti, Uwais Bashir; El-Tanani, Mohamed; Rizzo, Manfredi","year":2026,"journal":"Frontiers in pharmacology, 17, 1736380","doi":"10.3389/fphar.2026.1736380","pmid":"41743116","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16336","title":"Impaired intestinal cell proliferation parallels increased senescence after burn injury in aged mice.","authors":"Walrath, Travis M; Evans, Mara R; Meza Monge, Kenneth; Najarro, Kevin M; Orlicky, David J; Idrovo, Juan-Pablo; McMahan, Rachel H; Kovacs, Elizabeth J","year":2026,"journal":"American journal of physiology. Gastrointestinal and liver physiology, 330(1), G1-G9","doi":"10.1152/ajpgi.00176.2025","pmid":"41309057","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16337","title":"Tandem solubility enhancing tags enable the heterologous expression and in vitro maturation of a class IIa bacteriocin, clesteriocin a, identified in Candidatus Clostridium mucoides CM038.","authors":"Wambui, Joseph; Tasara, Taurai; Bigler, Laurent; Stephan, Roger","year":2026,"journal":"Frontiers in microbiology, 17, 1762029","doi":"10.3389/fmicb.2026.1762029","pmid":"41767563","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16338","title":"Automated Rapid Synthesis of High-Purity Head-to-Tail Cyclic Peptides via a Diaminonicotinic Acid Scaffold.","authors":"Wan, Feng; Hu, Chengrui; Xie, Pei; Yang, Xingxing; He, Xin; Pan, Yourong; Ning, Zuozhou; Li, Chengxi","year":2026,"journal":"Journal of the American Chemical Society, 148(1), 986-996","doi":"10.1021/jacs.5c16902","pmid":"41428388","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16339","title":"Ultrasound-propelled oncolytic biomimetic microbubbles as in situ vaccines reprogram tumor immunosuppressive microenvironment.","authors":"Wan, Li; Liang, Ping; Xia, Chunyu; Yu, Liliang; Tang, Rui; Li, Xintong; Tang, Chenchen; Wu, Nianhong; Huang, Zeyan; Chen, Jimei; Fu, Ruqian; Jiao, Mingke; Hu, Jie; Li, Pan; Li, Rui","year":2026,"journal":"Materials today. Bio, 37, 102923","doi":"10.1016/j.mtbio.2026.102923","pmid":"41756527","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16340","title":"Multiple protease-activated probody-drug conjugates for treating CD147-positive ovarian cancer with limited toxicity.","authors":"Wang, Bo; Zhang, Qiangzhe; Yang, Yuqing; Wang, Chenhui; Deng, Guiyu; Chen, Ying; Xu, Zichang; Chen, Zhinan; Zhou, Chuanzheng; Zhang, Sihe","year":2026,"journal":"Pharmacological research, 225, 108120","doi":"10.1016/j.phrs.2026.108120","pmid":"41620149","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16341","title":"Low-intensity pulsed ultrasound responsive phase-change nanoparticles loaded with rapamycin for targeted therapy of atherosclerotic plaques.","authors":"Wang, Dandan; Zhang, Xiaojing; Tang, Lingpeng; Wang, Shengnan; He, Yifang; Liu, Jiamin; Wang, Yanli; Zhang, Shijie; Lai, Jiangqiong; Lyu, Guorong","year":2026,"journal":"RSC advances, 16(2), 1078-1094","doi":"10.1039/d5ra09347c","pmid":"41496825","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16342","title":"APD6: the antimicrobial peptide database is expanded to promote research and development by deploying an unprecedented information pipeline.","authors":"Wang, Guangshun; Schmidt, Cindy; Li, Xia; Wang, Zhe","year":2026,"journal":"Nucleic acids research, 54(D1), D363-D374","doi":"10.1093/nar/gkaf860","pmid":"40927993","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The APD6 platform now houses 5,188 peptide records, broken down into 3,306 natural, 1,380 synthetic, and 239 predicted antimicrobial peptides. The database introduces the most comprehensive antimicrobial peptide information pipeline (AMPIP) to date, covering the full research lifecycle from discovery through clinical trials. New positive and negative datasets for factors like pH stability, salt tolerance, serum effects, and resistance potential have been added to support more advanced AI prediction models beyond the current focus on activity and hemolysis alone.","whyItMatters":"With antibiotic resistance recognized as a major global health threat, antimicrobial peptides represent one of the most promising paths to next-generation antibiotics. A centralized, comprehensive database like APD6 accelerates research by giving scientists ready access to curated peptide data, AI-training datasets, and clinical pipeline information — potentially shortening the timeline from peptide discovery to therapeutic use.","specificNumbers":"","methodology":"The researchers consolidated and expanded an existing peptide database platform, curating peptide records from published literature and computational predictions. They refined classification schemes for natural, synthetic, and predicted antimicrobial peptides, and built an information pipeline that systematically organizes data from discovery through clinical application.","limitations":"The database relies on published literature, so peptides from unpublished or proprietary research are not included. AI prediction datasets are still limited compared to the complexity of real-world therapeutic development. The database catalogs peptide properties but does not replace the need for experimental validation of any individual peptide's clinical potential."},{"rthcId":"RPEP-16343","title":"Rabies Virus Glycoprotein-Decorated Liposomes in Thermosensitive Nasal Spray Gels: Facilitating Retrograde Neural Transport for Targeted Trigeminal Neuralgia Therapy.","authors":"Wang, Guanlin; Kong, Xi; Li, Xiaofan; Chen, Chuangxin; Zhang, Kaiqing; Zhou, Yue; Yue, Xiao; Peng, Siyuan; Wu, Wentao; Wang, Wenhao; Zhao, Ziyu; Huang, Ying; Pan, Xin; Wu, Chuanbin; Zhang, Xuejuan","year":2026,"journal":"ACS nano, 20(5), 4027-4045","doi":"10.1021/acsnano.5c12628","pmid":"41579084","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16344","title":"Combination of aztreonam, colistin and tigecycline in the treatment of neonatal carbapenemase-producing Enterobacteriaceae infection: a case report.","authors":"Wang, Han; Tan, Yangyang","year":2026,"journal":"BMC pediatrics, 26(1)","doi":"10.1186/s12887-026-06511-4","pmid":"41566427","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The combination of aztreonam, colistin (polymyxin), and tigecycline successfully controlled a carbapenem-resistant Enterobacteriaceae (CRE) infection complicated by pneumonia and renal impairment in a neonate. The infant required invasive mechanical ventilation initially but showed improved respiratory function, managed spontaneous breathing, and was eventually discharged without significant adverse events.\n\nThe authors emphasize that combining peptide antibiotics (polymyxins) with other drug classes effective against resistant gram-negative bacteria can lower mortality in neonatal CRE pneumonia.","whyItMatters":"Carbapenem-resistant infections in newborns are life-threatening and extremely difficult to treat because these bacteria resist nearly all standard antibiotics. Colistin (polymyxin) is often called a 'last resort' antibiotic, but safety data in neonates is very limited. This case provides real-world evidence that colistin-based combination therapy can be both effective and tolerable in this vulnerable population — information desperately needed by NICU physicians facing these infections.","specificNumbers":"","methodology":"This is a single-patient retrospective case report analyzing clinical data from a neonate with CRE-related pneumonia and renal impairment treated in a NICU. The authors assessed clinical outcomes, respiratory status (including pulmonary ultrasound), and adverse events during treatment with the triple antibiotic combination.","limitations":"This is a single case report — the lowest level of clinical evidence. Results from one patient cannot be generalized. The long-term effects of colistin and tigecycline exposure on neonatal development were not assessed. No control comparison was possible. The contribution of each individual antibiotic to the outcome cannot be determined from a combination regimen."},{"rthcId":"RPEP-16345","title":"Hyperbaric oxygen therapy for osteoporosis: A systematic review of preclinical evidence and mechanisms.","authors":"Wang, Hao; Ma, Xiao; Sun, Yang; Guo, Zhihao; Wang, Jincheng; Sun, Mingli","year":2026,"journal":"Bone, 205, 117772","doi":"10.1016/j.bone.2025.117772","pmid":"41483655","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16346","title":"Self-Powered Anti-Interference Photoelectrochemical Immunosensor Enabled by a Ferroelectric Hybrid Coupled with a Platinum-Doped Peptide Hydrogel.","authors":"Wang, Hao; Zhao, Ying; Cai, Zhiyue; Fan, Gao-Chao; Luo, Xiliang","year":2026,"journal":"Analytical chemistry, 98(4), 2859-2869","doi":"10.1021/acs.analchem.5c05611","pmid":"41527244","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16347","title":"One-pot integration of functional molecules into polyphenol-peptide supramolecular self-assembly coatings with diverse and customizable functionalities.","authors":"Wang, Hongxiang; Huo, Kaiyuan; Hao, Feijing; Zan, Xingjie; Zhang, Guangyu; Li, Na","year":2026,"journal":"Colloids and surfaces. B, Biointerfaces, 259, 115361","doi":"10.1016/j.colsurfb.2025.115361","pmid":"41406680","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16348","title":"Heart failure in China: a macroeconomic modelling study of intervention strategies.","authors":"Wang, Hua; Zhou, Huiyi; Chai, Ke; Yan, Shaohua; Liu, Yujia; Kuhn, Michael; Prettner, Klaus; Cao, Zhong; Du, Minghui; Wang, Ting; Zeng, Ping; Wu, Jing; Chen, Simiao; Yang, Jiefu","year":2026,"journal":"European heart journal, 47(8), 974-984","doi":"10.1093/eurheartj/ehaf992","pmid":"41355346","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16349","title":"Silver nanoparticle-antimicrobial peptide supramolecular nanocomposite coating improves implant osseointegration under mechanical loading.","authors":"Wang, Huihui; Fischer, Nicholas G; Guan, Yunlin; Li, Kun; Cai, Hao; Deng, Yunyun; Ye, Zhou; Sang, Ting","year":2026,"journal":"Nanomedicine (London, England), 21(3), 363-373","doi":"10.1080/17435889.2026.2614548","pmid":"41537579","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16350","title":"Activation of the YAP1/pSTAT3/NRP1 axis in peritendinous sensory nerves promotes tendon healing.","authors":"Wang, Jiayi; Wang, Fan; Liu, Jingwen; Xiao, Yao; Li, Zhaoyang; Liu, Xiaonan; Zhang, Peilin; Wang, Fei; Cui, Wenguo; Liu, Shen","year":2026,"journal":"Science advances, 12(8), eaec1272","doi":"10.1126/sciadv.aec1272","pmid":"41706840","tags":[],"studyType":"animal","evidenceStrength":"preliminary","keyFinding":"Researchers discovered that electrical stimulation activates a signaling pathway (YAP1/pSTAT3/NRP1) in sensory neurons that promotes the growth of CGRP-positive nerve fibers into healing tendons. Building on this finding, they engineered a bifunctional piezoelectric patch made from P(VDF-TrFE) and regenerated silk fibroin composites that, when activated by ultrasound, generates localized electrical signals to drive sensory nerve and blood vessel growth while simultaneously reducing tissue adhesion.\n\nIn both rat and Bama minipig models of tendon injury, the patch markedly enhanced tendon regeneration and reduced adhesion scores by approximately 50% compared to controls.","whyItMatters":"Tendon injuries heal slowly and are often complicated by adhesions that limit joint mobility. This research identifies a specific molecular mechanism — the neuropeptide CGRP acting through electrically activated sensory nerves — that drives tendon repair, and translates it into a practical wearable patch. If validated in humans, this approach could offer a non-drug strategy for improving surgical tendon repair outcomes.","specificNumbers":"","methodology":"The researchers first used cell-based experiments to identify the YAP1/pSTAT3/NRP1 signaling pathway in sensory neurons responding to electrical stimulation. They then engineered a piezoelectric patch combining two functional layers — one generating electrical signals under ultrasound and another providing lubrication to prevent adhesion. The patch was tested in tendon injury models in both rats and Bama minipigs, assessing tendon healing quality and adhesion formation.","limitations":"This is an animal study conducted in rats and minipigs, and results may not directly translate to human tendon injuries. The study does not report long-term outcomes beyond the healing period assessed, and the ultrasound activation protocol would need optimization for clinical use."},{"rthcId":"RPEP-16351","title":"An Optimized Strategy for Random Peptide Library Construction Facilitates Screening of HBc-Binding Peptides via Yeast Surface Display.","authors":"Wang, Jin-Lan; Hu, Yu-Zhu; Li, Jie; Chen, Lei; Xiang, Lei; Long, Shao-Yuan; Xu, Wen; Zou, Yu-Qian; Huang, Ai-Long; Cui, Jing; Lei, Ling; Hu, Jie-Li","year":2026,"journal":"Biotechnology journal, 21(3), e70201","doi":"10.1002/biot.70201","pmid":"41761944","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16352","title":"Neuropeptide F-expressing neurons in Drosophila constitute centrifugal pathway to optic lobes.","authors":"Wang, Jing; Lehmann, Fritz-Olaf","year":2026,"journal":"PloS one, 21(2), e0343221","doi":"10.1371/journal.pone.0343221","pmid":"41758798","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Using GFP genetic labeling and microscopic imaging, approximately 50 NPF-expressing neurons were identified in the adult Drosophila brain, organized into five major anatomical clusters with distinct projection patterns targeting different brain regions.\n\nBeyond previously known P1, P2, and L1 neurons, the study identified two ventrolateral NPF-expressing neurons per hemisphere. These neurons have cell bodies in the protocerebrum but project centrifugally to the optic lobes (visual processing centers), positioning them as a potential neural link between the NPF neuromodulatory system and changes in visual attention — a connection not previously described.","whyItMatters":"NPF in flies is the functional equivalent of neuropeptide Y (NPY) in humans — a peptide deeply involved in appetite, anxiety, reward, and sleep. Mapping the NPF circuit in Drosophila provides a model for understanding how neuropeptide systems orchestrate behavior across the brain. The discovery of NPF neurons projecting to visual centers suggests that internal states (like hunger) can modulate sensory processing — a principle likely conserved in mammals.","specificNumbers":"","methodology":"The study used genetic labeling with GFP (green fluorescent protein) driven by NPF promoter sequences in Drosophila melanogaster, combined with confocal microscopic imaging and morphometric analysis. Neurons were classified by soma size, location, and arborization (branching) patterns across the adult brain.","limitations":"This is an anatomical mapping study in fruit flies, so direct translation to mammalian or human brain circuits is limited. The study describes neuron morphology and projections but does not test functional roles of the newly identified neurons. The GFP labeling may not capture all NPF-expressing neurons if expression levels vary across developmental or physiological states."},{"rthcId":"RPEP-16353","title":"Electrophysiological Characterization of Murine Vestibular Efferent Neurons and Modulation by Acute Peripheral Vestibular Deprivation.","authors":"Wang, Jinyu; Xu, Mengfan; Zhang, Lei; Liu, Wenjie; Wang, Siyue; Wang, Liqin; Cong, Ning; Li, Geng-Lin; Wang, Jing","year":2026,"journal":"Neuroscience bulletin, 42(3), 589-604","doi":"10.1007/s12264-025-01502-4","pmid":"40965807","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16354","title":"Efficacy and Safety of Dapagliflozin in Patients Over 75 Years Old With Heart Failure With Preserved Ejection Fraction: A Retrospective Study.","authors":"Wang, Juan; Li, Zhanliang; Zhu, Guiyue","year":2026,"journal":"British journal of hospital medicine (London, England : 2005), 87(2), 50721","doi":"10.31083/BJHM50721","pmid":"41762096","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16355","title":"Chitosan Nanoparticle Delivery Enhances the Antibacterial Performance and Bioactivity of Bovine Lactoferricin against Staphylococcus aureus-Associated Mastitis.","authors":"Wang, Kaiming; Gao, Yumeng; Jiang, Zhenlin; Tong, Jinjin; Zhang, Hua","year":2026,"journal":"Journal of agricultural and food chemistry, 74(1), 1422-1436","doi":"10.1021/acs.jafc.5c08818","pmid":"41420602","tags":["antimicrobial-peptides","lactoferricin","nanoparticle-delivery"],"studyType":"Preclinical (In Vitro + Animal)","evidenceStrength":"Moderate","keyFinding":"Encapsulating bovine lactoferricin (BLfcin) — an antimicrobial peptide from milk — in chitosan nanoparticles significantly enhanced its antibacterial activity against S. aureus and E. coli compared to the free peptide. The nanoparticles were 101–136 nm in size with 72% encapsulation efficiency.\n\nIn a mouse model of mastitis (breast infection), the BLfcin nanoparticles reduced bacterial load, decreased mammary inflammation, and boosted antioxidant enzyme levels without causing toxicity. Transcriptomic analysis revealed that the nanoparticle formulation suppressed bacterial genes related to ribosomes, ABC transporters, and two-component signaling systems — explaining the enhanced killing.","whyItMatters":"Mastitis is the most costly disease in dairy farming, and antibiotic overuse for treatment drives antimicrobial resistance. Lactoferricin is a natural antimicrobial peptide found in milk itself, making it an appealing antibiotic alternative. But like many peptides, free BLfcin is unstable and breaks down quickly. Wrapping it in chitosan nanoparticles solves this problem — improving stability, activity, and efficacy in living animals. This represents a practical, antibiotic-free approach to one of agriculture's biggest infection problems.","specificNumbers":"NPs 101.2–135.9 nm · zeta potential +19.83 to +21.37 mV · 72.18% encapsulation efficiency · improved activity vs S. aureus + E. coli · reduced bacterial burden in mouse mastitis · no toxicity observed","methodology":"BLfcin was loaded into chitosan nanoparticles and characterized for size, charge, and encapsulation efficiency. Antibacterial activity was tested in vitro against S. aureus and E. coli. Transcriptomic analysis identified bacterial gene expression changes caused by BLfcin NPs. Efficacy was validated in a murine mastitis model, measuring bacterial burden, inflammatory markers, antioxidant enzyme levels, and tissue toxicity.","limitations":"Mouse mastitis models don't perfectly replicate bovine udder physiology. The study does not test the nanoparticles in actual dairy cattle. Long-term stability of the nanoparticle formulation during storage is not addressed. The transcriptomic analysis was performed in vitro and may not capture all in vivo bacterial responses. Cost-effectiveness compared to conventional antibiotics is not evaluated."},{"rthcId":"RPEP-16356","title":"Conserved region amino acid mutations in Calcin: Altering the RyR structural-functional relationship.","authors":"Wang, Lianbo; Hua, Xiaoyu; Ma, Xiaofen; Wang, Jianguo; Xiao, Li; Wang, Shumin; Liu, Hao; Zhao, Yangfei; Valdivia, Héctor H; Xiao, Liang; Wang, Jinming","year":2026,"journal":"Toxicon : official journal of the International Society on Toxinology, 271, 108967","doi":"10.1016/j.toxicon.2025.108967","pmid":"41429375","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16357","title":"Ligand-Based Computational Design and Preclinical Evaluation of a Novel Cyclic Peptide Radiotracer for FGFR1-Targeted PET Imaging in Uveal Melanoma.","authors":"Wang, Ling; Zhu, Xue; Yu, Mengxi; Zhu, Hong; Huang, Zhihong; Xue, Yan; Wang, Shuang; Jiao, Yang; Li, Yonghao; Lian, Bin; Xu, Chunwei; Hao, Yue; Fang, Jing; Wang, Ke","year":2026,"journal":"ACS sensors, 11(2), 1663-1672","doi":"10.1021/acssensors.5c04161","pmid":"41661730","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16358","title":"Transmembrane mechanisms and targeted delivery strategies of self-assembling peptides in tumor therapy.","authors":"Wang, Luxi; Tang, Ying; Mao, Yifei; Chen, Rui; Luo, Xin; Xu, Junrong; Li, Chunlai; Xie, Beibei; Li, Peng","year":2026,"journal":"International journal of biological macromolecules, 347, 150739","doi":"10.1016/j.ijbiomac.2026.150739","pmid":"41651271","tags":["peptide-drug-delivery","cancer"],"studyType":"review","evidenceStrength":"moderate","keyFinding":"This review catalogs six primary mechanisms by which self-assembling peptide (SAP) nanomedicines cross cell membranes to deliver cancer drugs: (1) classical endocytosis, (2) fluoride-modified transmembrane transport, (3) macropinocytosis-mediated transport, (4) flexible cyclic peptide-mediated transport, (5) receptor-mediated transport, and (6) cell-penetrating peptide-mediated endocytosis.\n\nFor tumor-specific targeting, SAP nanomedicines incorporate three categories of targeting peptides: those that home to tumor cells directly, those that target tumor blood vessel endothelial cells, and those that target the tumor microenvironment. The review emphasizes that combining self-assembly properties with specific targeting peptides enables precise drug delivery to tumors while minimizing damage to healthy tissue.","whyItMatters":"Cancer drugs often damage healthy cells alongside tumors, causing severe side effects. Self-assembling peptides offer a potential solution: they can form nanostructures that encapsulate drugs, cross cell membranes efficiently, and deliver their cargo specifically to tumors. Understanding the different transmembrane mechanisms and targeting strategies is essential for designing the next generation of peptide-based cancer nanomedicines. This review provides a comprehensive roadmap for researchers working to translate SAP technologies from the lab to clinical use.","specificNumbers":"6 transmembrane mechanisms cataloged · 3 types of tumor-targeting peptides · biocompatible and biodegradable · multiple delivery strategies for clinical translation","methodology":"Comprehensive literature review of published research on self-assembling peptide nanomedicines in cancer therapy, covering transmembrane transport mechanisms, targeting peptide strategies, and current challenges in clinical translation.","limitations":"As a review, this paper summarizes existing research rather than presenting new experimental data. Most SAP nanomedicine systems discussed remain preclinical. The clinical translation challenges highlighted — including stability, manufacturing scalability, and regulatory pathways — are significant and largely unresolved. The review may not capture the most recent developments given the rapidly evolving field."},{"rthcId":"RPEP-16359","title":"A Spatiotemporally Controlled Nanoplatform for Photothermal BRD4 Degradation Enables Synergistic Cancer Immunotherapy.","authors":"Wang, Luyi; Wu, Jiasha; Ji, Rui; Qiang, Sufeng; Shen, Yulin; Zuo, Yan; Jian, Shiqin; Liu, Siyao; Xu, Fusheng; Hu, Honggang; Hu, Xiaochun","year":2026,"journal":"Advanced science (Weinheim, Baden-Wurttemberg, Germany), e23928","doi":"10.1002/advs.202523928","pmid":"41662485","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The PCN-CuS-JQ/RGD nanoplatform executes a multi-step delivery cascade: RGD peptide targets integrin-overexpressing tumor cells → the MOF carrier decomposes intracellularly, releasing CuS-JQ/RGD units → these enter the nucleus and bind BRD4 → NIR-II laser irradiation triggers photothermal BRD4 degradation. This process simultaneously induces immunogenic cell death (ICD) and downregulates PD-L1, creating synergy with anti-PD-L1 checkpoint blockade therapy. In bilateral tumor mouse models, the combination significantly enhanced immunotherapy efficacy beyond either approach alone.","whyItMatters":"Targeted protein degradation is one of the most exciting frontiers in cancer therapy, but current approaches (PROTACs) lack precise control and cause toxicity. By using light activation with peptide-guided targeting, this platform achieves spatiotemporal control — degrading cancer proteins only where and when the light is applied. The bonus of enhancing immunotherapy makes this a potentially transformative multi-modal approach to cancer treatment.","specificNumbers":"","methodology":"Preclinical mouse cancer model study. The nanoplatform was constructed using an Fe-porphyrin metal-organic framework (PCN(Fe)) as the carrier, decorated with CuS photothermal agents, BRD4 inhibitor JQ1, and RGD tumor-targeting peptide. MRI imaging confirmed tumor targeting. A 1064 nm NIR-II laser was used for photothermal activation. Anti-tumor efficacy was assessed in bilateral tumor-bearing mice with and without anti-PD-L1 combination therapy.","limitations":"This is a preclinical mouse study, and translation to human cancer treatment faces significant challenges including light penetration depth for deep tumors, scalability of nanoplatform manufacturing, and potential toxicity of the multi-component system. The 1064 nm laser can penetrate tissue but has limits for deep-seated tumors. Long-term safety of the degradation products and the MOF carrier has not been assessed. The bilateral tumor model, while powerful, is a simplified representation of human cancer metastasis."},{"rthcId":"RPEP-16360","title":"Impact of Glucagon-Like Peptide-1 Receptor Agonists on Liver-Related Outcomes, Laboratory and Physiologic Parameters in Metabolic Dysfunction-Associated Steatohepatitis: A Systematic Review and Meta-Analysis.","authors":"Wang, Mei-Jun; Jiang, Yu-Nuo; Li, Pei-Pei; Wu, Yuan-Jie","year":2026,"journal":"Diabetes, metabolic syndrome and obesity : targets and therapy, 19, 565093","doi":"10.2147/DMSO.S565093","pmid":"41710713","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 25 randomized controlled trials (n=2,481), GLP-1 receptor agonists significantly increased the resolution of MASH without fibrosis worsening, with an odds ratio of 4.04 (95% CI: 2.69–6.05). However, fibrosis improvement without steatohepatitis worsening did not reach statistical significance.\n\nSubgroup analysis of semaglutide trials showed improved NASH Activity Score (NAS ≥2-point decrease) and steatosis grade but no significant changes in weight, waist circumference, liver enzymes, or lipid levels. Trial sequential analysis confirmed the evidence was sufficient for MASH resolution (required information size = 197 patients reached) but insufficient for fibrosis improvement (required 1,693 patients, not yet reached). GRADE assessment rated the evidence as high certainty for both primary outcomes.","whyItMatters":"MASH affects millions of people worldwide and is a leading cause of liver transplantation, yet treatment options have been extremely limited until recently. GLP-1 receptor agonists are already widely prescribed for diabetes and obesity, so confirming their liver benefits could help patients with overlapping conditions. However, the finding that fibrosis doesn't improve is crucial — fibrosis is the strongest predictor of liver-related death, meaning GLP-1 drugs alone may not be enough for patients with advanced liver scarring.","specificNumbers":"","methodology":"This was a PRISMA 2020-compliant systematic review and meta-analysis of 25 randomized controlled trials. Risk of bias was assessed using ROB 2, and evidence certainty was evaluated using the GRADE framework. Trial sequential analysis was performed to check whether enough data existed to draw firm conclusions. Primary outcomes were MASH resolution without fibrosis worsening and fibrosis improvement without steatohepatitis worsening. The protocol was pre-registered in PROSPERO.","limitations":"While the meta-analysis included 25 RCTs, the trial sequential analysis showed that insufficient data exists to draw firm conclusions about fibrosis improvement — larger trials are still needed. The included studies varied in GLP-1RA type, dose, duration, and patient population. Liver biopsy, the gold standard for assessing histological outcomes, was not available in all trials. Most trials had relatively short follow-up periods, and MASH and fibrosis are chronic conditions that progress over years to decades."},{"rthcId":"RPEP-16361","title":"Nucleus-Localizing Coacervates Synergize with Chemotherapy for the Treatment of Drug-Resistant Ovarian Tumors.","authors":"Wang, Meixin; Yang, Shi; Xu, Yifei; Wang, Jianwei; Zhang, Yage; Ma, Qingming; Feng, Chuanliang; Song, Yang","year":2026,"journal":"Biomacromolecules","doi":"10.1021/acs.biomac.5c02014","pmid":"41728903","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16362","title":"An oral vaccine based on stable peptide-chitosan conjugate targeting DEC-205 for cancer immunotherapy.","authors":"Wang, Mengfan; Ye, Xiaoyun; Li, Wanqiong; Chen, Danhong; Zhao, Xin; Shi, Peishang; Sui, Xinghua; Liu, Juan; Luo, Feiyu; Yang, Xin; Niu, Xiaoshuang; Xiao, Youmei; Qian, Yuzhen; Ning, Haoming; He, Zhuoying; Li, Huihao; Su, Ye; Zeng, Wenxuan; Chen, Guanyu; Gao, Yanfeng","year":2026,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 389, 114416","doi":"10.1016/j.jconrel.2025.114416","pmid":"41276186","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16363","title":"Intranasal administration of broad-spectrum macrocyclic peptide inhibitor protects against SARS-CoV-2 Omicron variants.","authors":"Wang, Min; Yang, Jinyue; Tan, Yahong; Yuan, Shuofeng; Shi, Guoli; Peng, Qi; Li, Yongqi; Poon, Vincent Kwok-Man; Chan, Chris Chung-Sing; Xiao, Na; Zhang, Anna Jinxia; Xie, Yubin; Li, Junhua; Luo, Hao; Fu, Yaning; Chen, Yong; Compton, Alex A; Zhang, Youming; Yang, Yang; Gao, George Fu; Hou, Hongwei; Chan, Jasper Fuk-Woo; Yin, Yizhen; Shi, Yi","year":2026,"journal":"Nature communications, 17(1), 1753","doi":"10.1038/s41467-026-68462-9","pmid":"41587975","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16364","title":"Post-semaglutide weight regain in females with obesity: Associations with gut microbiota, bile acid metabolism, and central nervous system.","authors":"Wang, Ning; Guo, Haonan; Song, Lin; Wang, Jingyue; Hu, Shuyuan; Wang, Mingxi; Zhang, Duowen; Jing, Yingyu; Zhang, Yifan; Wang, Mengjun; Wang, Ting; Sun, Bo","year":2026,"journal":"Diabetes, obesity & metabolism","doi":"10.1111/dom.70571","pmid":"41705640","tags":["glp-1-agonists"],"studyType":"clinical-trial","evidenceStrength":"moderate","keyFinding":"After 36 weeks of semaglutide treatment, 28 women with obesity lost an average of 16.9 kg. But within 12 weeks of stopping the drug, 71.4% regained weight (averaging +5.1 kg) and 78.5% experienced appetite rebound (≥30% increase in hunger scores plus ≥300 kcal/day increase in intake).\n\nThe mechanistic investigation — using both human data and parallel rat studies — found that weight regain was accompanied by gut microbiota dysbiosis (increased Firmicutes/Bacteroidota ratio), decreased ursodeoxycholic acid levels, reduced hypothalamic TGR5 expression, and reactivation of hunger-promoting brain signals (AgRP/NPY) while satiety signals (POMC/MC4R) weakened. However, some improvements in liver and fat tissue metabolism partially persisted through maintained AMPK/SIRT1 activation.","whyItMatters":"The biggest criticism of GLP-1 drugs is that weight returns when you stop taking them. This study is one of the first to systematically explain WHY that happens — tracing the mechanism from gut bacteria changes to bile acid shifts to brain appetite center reactivation. Understanding this pathway could lead to strategies that prevent post-drug weight regain.","specificNumbers":"n=28 women · 36 weeks treatment · 12 weeks withdrawal · Weight loss: -16.9 ± 4.8 kg · Weight regain: +5.1 ± 1.6 kg in 71.4% · Appetite rebound: 78.5% · ≥300 kcal/day increase","methodology":"Prospective, single-arm interventional study in 28 women with obesity receiving semaglutide 2.4 mg/week for 36 weeks followed by 12-week withdrawal monitoring. Parallel animal studies used high-fat diet female rats with 4-week semaglutide intervention and 4-week withdrawal. Measured body weight, metabolic parameters, gut microbiota composition (16S sequencing), bile acid profiles, and hypothalamic gene expression.","limitations":"Small sample size (28 women) with no control group in the human portion. Single-arm design means natural weight fluctuations can't be separated from drug withdrawal effects. Only studied women. The 12-week withdrawal period may not capture the full trajectory of weight regain. Animal model findings may not fully translate to humans. Gut microbiota changes are correlative, not definitively causal."},{"rthcId":"RPEP-16365","title":"GPC3127-136-HSP70 mRNA Nanovaccine in Combination with Anti-PD-L1 Therapy Elicits Robust T-Cell-Mediated Immunity against Hepatocellular Carcinoma.","authors":"Wang, Peng; Dong, Rui; Zhang, Mengjie; Liao, Jingyi; Liu, Paiyu; Lei, Bo; Cui, Hongjuan; Peng, Yanmeng; Ni, Bing","year":2026,"journal":"ACS biomaterials science & engineering, 12(2), 1229-1244","doi":"10.1021/acsbiomaterials.5c01444","pmid":"41493068","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16366","title":"Late-stage Tyrosine ortho-C(sp2)-H Alkenylation for Macrocyclic Peptide SuFEx Proximity Labeling and Targeted Degradation.","authors":"Wang, Peng; Wang, Kai; Yin, Shuailong; Liu, Xiaoyan; Xie, Wuyan; Li, Haohui; Yang, Xiuxiu; Zhu, Qing","year":2026,"journal":"Angewandte Chemie (International ed. in English), 65(6), e24685","doi":"10.1002/anie.202524685","pmid":"41452223","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16367","title":"Unraveling Endogenous Antimicrobial Peptides from Bacillus cereus 0-9 Governed by the Global Transcriptional Regulator AbrB.","authors":"Wang, Pengfei; Ma, Yuansong; Wu, Jiasong; Xu, Jingbo; Zhang, Bofei; Huang, Qiubin; Wang, Shaowei; Liu, Fengying; Xu, Yinbiao; Wang, Gang","year":2026,"journal":"Journal of agricultural and food chemistry, 74(4), 3684-3694","doi":"10.1021/acs.jafc.5c13125","pmid":"41563847","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16368","title":"The Ly6ghigh Neutrophil Subset Dictates Breast Cancer Lung Metastasis via CD8+ T Cell Death.","authors":"Wang, Rui; Liu, Xiaoqi; Hou, Yixuan; Chen, Shanchun; Liu, Yongcan; Lu, Zexiu; Chang, Chao; Meng, Die; Chen, Jing; Cui, Xiaojiang; Shi, Zhengrong; Wan, Xueying; Liu, Manran","year":2026,"journal":"Cancer communications (London, England), 46, 0003","doi":"10.34133/cancomm.0003","pmid":"41625479","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16369","title":"Probiotic and antibacterial properties of recombinant Lactococcus lactis expressing the fusion antimicrobial peptides BMAP18-BSN37 in mice and chickens.","authors":"Wang, Ruibiao; Lin, Yukai; Xia, Yu; Liu, Suxian; Feng, Doudou; Li, Siyang; Zhou, Tengyue; Sun, Huarun; Shen, Jiyuan; Wen, Bo; Li, Minghui; Liao, Chengshui; Qin, Baoliang; Hu, Jianhe; Ma, Yuanfang; Ding, Ke; Wang, Lei","year":2026,"journal":"Poultry science, 105(4), 106507","doi":"10.1016/j.psj.2026.106507","pmid":"41616534","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16370","title":"Ameliorative effects of Atractylodes macrocephala insoluble dietary fiber on loperamide-induced functional constipation in rats.","authors":"Wang, Senye; Feng, Wenjing; Tu, Suxing; Li, Jie; Liu, Yali; Wang, Jinmei; Zhang, Yu; Kang, Wenyi","year":2026,"journal":"Food research international (Ottawa, Ont.), 227, 118256","doi":"10.1016/j.foodres.2025.118256","pmid":"41652675","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16371","title":"Plant Peptides on the Rise: From Historical Insight to Future Applications.","authors":"Wang, Shunxi; Zhang, Jinghua; Chen, Minghui; Zhang, Bokai; Zhao, Huina; Wu, Liuji","year":2026,"journal":"Plant biotechnology journal","doi":"10.1111/pbi.70613","pmid":"41729009","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16372","title":"Antimicrobial Peptide Nanoassemblies: Design, Response Mechanisms, and Biomedical Applications.","authors":"Wang, Tao; Ji, Linbao; Zhang, Yucheng; Niu, Zhili; Jiang, Xiaoyi; Wang, Xingyao; Zhang, Qingtai; Zhang, Yuting; Tan, Peng; Feng, Yue; Ma, Xi; Sun, Zhihong","year":2026,"journal":"Molecules (Basel, Switzerland), 31(3)","doi":"10.3390/molecules31030518","pmid":"41683494","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16373","title":"Overcoming Proteolytic Instability in a β-Turn Antimicrobial Peptide via Cyclization and Stereochemical Inversion to Combat MDR Bacteria.","authors":"Wang, Taoran; Tian, Long; Zeng, Jiangmin; Ning, Ziyao; Zhang, Li; Zhao, Chunhui; Jiang, Shuyuan; Zeng, Chunlan; Han, Jiaqi; Luan, Liang; Ye, Weifeng; Meng, Qingbin","year":2026,"journal":"Journal of medicinal chemistry, 69(4), 4726-4744","doi":"10.1021/acs.jmedchem.5c03372","pmid":"41700024","tags":["antimicrobial-peptide","cyclization","drug-resistance"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"By combining cyclization (closing the peptide into a ring) and D-amino acid substitution (using mirror-image amino acids), researchers transformed a linear antimicrobial peptide called P-07 into PT-17 — a dramatically more stable version that resists enzymatic breakdown. PT-17 retained broad-spectrum killing activity against multidrug-resistant (MDR) bacteria, showed a high therapeutic index (meaning it kills bacteria at much lower concentrations than those toxic to human cells), disrupted bacterial membranes rapidly, showed low potential to trigger resistance, and worked synergistically with conventional antibiotics. In mice infected with MDR E. coli, PT-17 significantly reduced bacterial loads in major organs with no detectable toxicity.","whyItMatters":"Antibiotic resistance is a global crisis, and antimicrobial peptides (AMPs) represent one of the most promising alternatives to conventional antibiotics. However, natural AMPs are rapidly destroyed by enzymes in the body. This study demonstrates that two stabilization strategies — cyclization and D-amino acid substitution — can be combined to make β-turn AMPs dramatically more stable without sacrificing their ability to kill resistant bacteria. This provides a practical blueprint for turning promising lab peptides into viable drug candidates.","specificNumbers":"PT-17 lead candidate · Broad-spectrum activity against MDR pathogens · High therapeutic index · Significant reduction of MDR E. coli in mouse organs · Synergy with conventional antibiotics · No detectable toxicity in mice","methodology":"Starting from a linear β-turn antimicrobial peptide (P-07), the researchers created multiple cyclized derivatives using disulfide bonds and lactam bonds, plus versions with D-amino acid substitutions. They tested stability against enzymatic degradation, antimicrobial activity against MDR bacteria, membrane disruption speed, resistance development potential, and synergy with existing antibiotics. The lead compound PT-17 was then tested in a mouse infection model using MDR E. coli.","limitations":"This is preclinical research — no human trials have been conducted. The mouse infection model, while informative, may not fully predict clinical performance. Specific MIC values and quantitative organ bacterial load reductions were not detailed in the abstract. Manufacturing scalability and cost of the cyclized peptide are not addressed. Long-term safety data are not available."},{"rthcId":"RPEP-16374","title":"Adjunctive diabetes therapies and cardiovascular protection in type 1 diabetes: tackling the challenging Tchaikovsky piece.","authors":"Wang, Wei Ting; Loh, Wann Jia","year":2026,"journal":"Current opinion in endocrinology, diabetes, and obesity, 33(1), 33-41","doi":"10.1097/MED.0000000000000940","pmid":"41123381","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16375","title":"Strategies for overcoming multiple barriers of oral administration of protein and peptide therapeutics.","authors":"Wang, Xiaofan; Wang, Keke; Fang, Yitan; Zhang, Youxi; Yi, Lixin; Li, Xiaohong; Zhao, Qinfu; Zhu, Xu; Cai, Shuang; Wan, Long","year":2026,"journal":"Materials today. Bio, 37, 102763","doi":"10.1016/j.mtbio.2026.102763","pmid":"41585434","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies four main gastrointestinal barriers to oral peptide delivery: harsh pH environment, enzymatic degradation, the mucus layer, and the intestinal epithelial barrier. Current strategies to overcome these include chemical modifications (like PEGylation and cyclization), permeation enhancers that temporarily open tight junctions, encapsulation techniques (enteric coatings, hydrogels), and novel delivery systems including ingestible microneedle devices and nanoparticle-based carriers.\n\nThe authors conclude that no single strategy adequately overcomes all four barriers, and that synergistic integration of multiple approaches — combining protection, permeation enhancement, and targeted delivery — is the most promising path toward effective oral peptide therapeutics.","whyItMatters":"The ability to take peptide drugs orally instead of by injection would dramatically improve patient compliance and quality of life for millions of people managing conditions like diabetes, obesity, and osteoporosis. Oral delivery could also reduce healthcare costs and expand access to peptide therapies in settings where injection-based treatment is impractical.","specificNumbers":"","methodology":"This is a comprehensive narrative review of the recent literature on oral delivery strategies for protein and peptide therapeutics. The authors surveyed and critically evaluated published research on chemical modifications, permeation enhancers, encapsulation techniques, and novel delivery systems, providing comparative analysis of each approach's advantages and limitations.","limitations":"As a review, this paper synthesizes existing research rather than generating new data. Many of the strategies discussed remain in preclinical stages, and the gap between laboratory success and commercial oral peptide products remains large. The review acknowledges that translating multi-barrier strategies into practical, scalable formulations is a major unresolved challenge."},{"rthcId":"RPEP-16376","title":"A Vibrio-susceptibility class of antimicrobial peptide Ajapocin via membranolytic pattern to combat \"non-cholera\" pathogens in vivo infection models.","authors":"Wang, Xiaofei; Hong, Xiao; Liu, Wanting; Xu, Yujun; Chen, Roushi; Chen, Fangyi; Wang, Ke-Jian; Wang, Luxi","year":2026,"journal":"Biochemical pharmacology, 247, 117766","doi":"10.1016/j.bcp.2026.117766","pmid":"41633430","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Ajapocin showed potent activity against V. parahaemolyticus and V. vulnificus with MICs of 6-12 μM — comparable to Polymyxin B. In vivo efficacy was demonstrated in both zebrafish (single dose, 1 mg/mL) and mouse models (multiple doses reduced bacterial burden and accelerated wound healing). No cytotoxicity was observed in ZF4 or HaCaT cells up to 32 μM. One week of daily intraperitoneal injection caused no hepatic or renal toxicity confirmed by histopathology and blood chemistry.\n\nThe mechanism involves targeting negatively charged bacterial membrane components, enhancing membrane permeation, inducing depolarization, and causing membrane destruction — a membranolytic pattern that is difficult for bacteria to develop resistance against.","whyItMatters":"Vibrio infections are a growing public health concern: they cause severe seafood-borne illness and can create life-threatening wound infections, particularly in people with liver disease or immune compromise. With antibiotic resistance increasing, antimicrobial peptides like Ajapocin offer an alternative that bacteria are unlikely to develop resistance against, while also addressing aquaculture safety where antibiotic overuse is a major concern.","specificNumbers":"","methodology":"Ajapocin was identified through sequence optimization of a marine-source peptide. In vitro activity was measured via MIC determination against V. parahaemolyticus and V. vulnificus, compared with Polymyxin B. In vivo testing used a zebrafish-Vibrio infection model and a mouse V. vulnificus-infected skin wound model. Safety was assessed via cell viability assays (ZF4, HaCaT cells) and 1-week intraperitoneal injection toxicity study with histopathology and blood chemistry. Mechanistic studies examined membrane interaction, permeation, depolarization, and damage.","limitations":"The mouse wound model used topical application, but systemic treatment for disseminated Vibrio infections was not tested. The 1-week toxicity study is short for assessing chronic safety. Only Vibrio species were tested — the spectrum of activity against other pathogens is unknown. The transition from animal models to human clinical use requires extensive development including pharmacokinetics, formulation optimization, and regulatory approval."},{"rthcId":"RPEP-16377","title":"Bioinspired lipid droplets nanoplatform for periodontitis therapy: Integrated antibacterial, mitochondrial repair, and immunomodulatory functions.","authors":"Wang, Xin; Ban, Chenfang; Li, Xuejing; Wang, Jin; Cao, Bangping; Wu, Wenjing; Zhang, Zhanwei; Su, Jiansheng","year":2026,"journal":"Materials today. Bio, 37, 102808","doi":"10.1016/j.mtbio.2026.102808","pmid":"41624519","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16378","title":"Liuwei Dihuang Formula ameliorates glycolipid metabolism in type 2 diabetic rats through an integrated analysis of gut microbiota and bile acids.","authors":"Wang, Xin; Zhang, Fangfei; Zhang, Jiahui; Du, Youyou; Zhang, Tiantian; Liu, Shiwen; Di, Xin","year":2026,"journal":"Journal of pharmaceutical and biomedical analysis, 268, 117181","doi":"10.1016/j.jpba.2025.117181","pmid":"41092499","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16379","title":"A GLP-1 receptor agonist semaglutide attenuates cardiac microvascular injury in HFD/STZ-induced diabetic mice.","authors":"Wang, Xinye; Wang, Xiaoting; Zhuang, Hong; Lu, Guangzhen; Zhao, Gang","year":2026,"journal":"European journal of pharmacology, 1011, 178429","doi":"10.1016/j.ejphar.2025.178429","pmid":"41344533","tags":[],"studyType":"animal","evidenceStrength":"preliminary","keyFinding":"Eight weeks of semaglutide treatment in diabetic ApoE-/- mice reversed cardiac microvascular damage caused by high-fat diet and streptozotocin-induced diabetes. Semaglutide preserved microvascular structure and density, reduced perivascular fibrosis, and protected through multiple molecular mechanisms: reducing advanced glycation end products (AGEs) and their receptors, activating the Nrf2/HO-1/NQO1 antioxidant pathway, inhibiting the MCP-1/CCR2a/NF-κB inflammatory pathway, lowering inflammatory cytokines, and reducing cell death (apoptosis).\n\nDiabetic mice showed disrupted cardiac microvascular architecture and reduced vessel density, both of which semaglutide attenuated or reversed.","whyItMatters":"Clinical trials have shown semaglutide reduces major cardiovascular events in diabetic patients, but the mechanisms aren't fully understood. This study reveals that semaglutide directly protects the heart's smallest blood vessels — the microvasculature — from diabetes-induced damage through multiple anti-inflammatory, antioxidant, and anti-apoptotic pathways. This microvascular protection may explain part of semaglutide's cardiovascular benefits observed in humans.","specificNumbers":"","methodology":"ApoE-/- mice (prone to cardiovascular disease) were given high-fat diet plus streptozotocin to induce diabetes, then treated with semaglutide for 8 weeks. Cardiac microvascular structure was assessed by scanning electron microscopy. CD31 expression (a blood vessel marker) was evaluated by immunofluorescence. Molecular pathways were analyzed by TUNEL staining (apoptosis), western blotting, and RT-qPCR for oxidative stress, inflammation, and apoptosis markers.","limitations":"This is a mouse study using ApoE-knockout mice with chemically induced diabetes, which may not fully replicate human diabetic cardiomyopathy. The 8-week treatment period is relatively short. Specific semaglutide doses and direct comparison to human equivalent doses are not detailed in the abstract. The multiple pathways identified make it difficult to determine which is most clinically significant."},{"rthcId":"RPEP-16380","title":"Efsubaglutide Alfa attenuates metabolic dysfunction-associated steatohepatitis in mice with improvements in second harmonic generation-derived fibrosis features.","authors":"Wang, Yahao; Wang, Zhihong; Yan, Guirui; Peng, Chuhang; Chen, Liping; Yan, Run; Wang, Qinghua","year":2026,"journal":"Diabetes, obesity & metabolism","doi":"10.1111/dom.70495","pmid":"41555840","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16381","title":"Olive-derived elenolic acid surpasses metformin and rivals liraglutide in managing blood glucose and obesity in a mouse model of type 2 diabetes.","authors":"Wang, Yao; Alkhalidy, Hana; Cao, Xinyi; Vaughan, Reagan; Rachi, Md Abu T; Xu, Bin; Kale, Balaji; Silte, Abeje; Rainville, Jennifer; Hodes, Georgia E; Zhang, Yan; Liu, Dongmin","year":2026,"journal":"The Journal of nutritional biochemistry, 150, 110206","doi":"10.1016/j.jnutbio.2025.110206","pmid":"41314560","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16382","title":"In silico optimized cell-penetrating peptides achieve transdermal siRNA delivery and regulate inflammatory environment in psoriasis.","authors":"Wang, Yefeng; Wu, Siwen; He, Yilin; Zhang, Jiani; Chen, Yujiao; Zhou, Lei; Li, Xiaopeng; Yang, Li","year":2026,"journal":"Biomaterials, 328, 123882","doi":"10.1016/j.biomaterials.2025.123882","pmid":"41343908","tags":[],"studyType":"preclinical","evidenceStrength":"preliminary","keyFinding":"Researchers used computational modeling to design cell-penetrating peptides (CPPs) optimized for transdermal delivery, then loaded them with siRNA targeting ADAM17 — a protein that drives TNF-α-mediated inflammation in psoriasis. The peptide carriers successfully penetrated the skin's stratum corneum, were taken up by immune cells in the dermis, and suppressed ADAM17 expression and TNF-α inflammatory responses.\n\nA skin-adhesive spray formulation containing the peptide-siRNA complexes ameliorated psoriatic pathology in both human 3D skin models and a mouse psoriasis model. Multiplex imaging revealed the peptide carriers reprogrammed immune-epithelial cell cross-talk in the tissue microenvironment.","whyItMatters":"Psoriasis treatment currently relies on systemic biologics (injected antibodies) or topical steroids. A spray-on peptide carrier that delivers gene-silencing siRNA directly through the skin could offer a non-invasive alternative that targets the root inflammatory cause. The computational optimization approach also demonstrates how AI/computational tools can accelerate peptide carrier design.","specificNumbers":"","methodology":"Four cationic cell-penetrating peptides were computationally designed and screened for stratum corneum diffusion properties. Therapeutic efficacy was validated in human cell-derived 3D skin models and a murine psoriasis model. A skin-adhesive spray formulation was developed for clinical applicability. ADAM17 downregulation, TNF-α suppression, and inflammatory microenvironment reprogramming were assessed by immunofluorescence, protein expression analysis, and multiplex imaging.","limitations":"Preclinical study using 3D skin models and mouse psoriasis models — human clinical efficacy is unknown. The translation from computational predictions to actual transdermal penetration in human skin may differ. Long-term safety of repeated transdermal siRNA/peptide carrier application is not assessed. The psoriasis model may not fully replicate human disease complexity."},{"rthcId":"RPEP-16383","title":"Effects of exogenous detemir and glargine insulin on the detection of endogenous C-peptide and endogenous insulin.","authors":"Wang, Yi-Ting; Ma, Yi-Fang; Zheng, Yao; Ou, Yang; Zhou, Yi-Kun","year":2026,"journal":"European journal of medical research, 31(1)","doi":"10.1186/s40001-026-03877-0","pmid":"41680836","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16384","title":"Bifunctional Peptides Generated by Optimising the Antimicrobial Activity of a Novel Trypsin-Inhibitory Peptide from Odorrana schmackeri.","authors":"Wang, Ying; Chai, Xinchuan; Zhang, Ying; Xing, Xueying; Jiang, Yangyang; Wang, Tao; Chen, Xiaoling; Wang, Lei; Zhou, Mei; Burrows, James F; Li, Na; Zhang, Xiaofei; Chen, Tianbao","year":2026,"journal":"Biomolecules, 16(1)","doi":"10.3390/biom16010148","pmid":"41594688","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16385","title":"Treatment of type 2 diabetes among medicare beneficiaries with and without alzheimer's disease: A retrospective cohort study.","authors":"Wang, Yingqi; Alexander, G Caleb; Mehta, Hemalkumar B","year":2026,"journal":"Journal of diabetes and metabolic disorders, 25(1), 25","doi":"10.1007/s40200-025-01838-8","pmid":"41510365","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 388,359 Medicare beneficiaries newly diagnosed with T2DM (9,584 with Alzheimer's), overall treatment initiation within one year was lower for individuals with AD. Those with AD who did start treatment were more likely to receive insulin and less likely to receive metformin, SGLT2 inhibitors, or GLP-1 receptor agonists.\n\nIn adjusted models, Alzheimer's disease was associated with lower odds of any antidiabetic treatment initiation and, among those who started treatment, lower odds of initiating newer agents like GLP-1 RAs and SGLT2 inhibitors. The findings reveal a treatment disparity that may have clinical consequences given emerging evidence of cardiovascular and neuroprotective benefits of these newer drug classes.","whyItMatters":"GLP-1 receptor agonists and SGLT2 inhibitors offer cardiovascular protection and potential neuroprotective benefits that could be especially valuable for Alzheimer's patients. The finding that this population is disproportionately excluded from these newer therapies — possibly due to complexity of care, perceived life expectancy, or prescriber caution — highlights a potential treatment gap that deserves clinical attention.","specificNumbers":"","methodology":"Retrospective cohort study using 20% Medicare Fee-for-Service claims data from 2016 to 2020. The primary outcome was initiation of any antidiabetic medication within one year of new T2DM diagnosis. The researchers examined initiation patterns across specific drug classes and used multivariable logistic regression to estimate adjusted odds ratios for the association between Alzheimer's status and treatment patterns.","limitations":"Claims data cannot capture the clinical reasoning behind prescribing decisions — physicians may have valid reasons for choosing insulin over newer agents in patients with cognitive impairment (e.g., injection simplicity with caregiver support, concerns about GI side effects). The study cannot determine whether the treatment differences led to different clinical outcomes. The data spans 2016-2020, before the most recent expansion of GLP-1 RA use."},{"rthcId":"RPEP-16386","title":"SGAC: a graph neural network framework for imbalanced and structure-aware AMP classification.","authors":"Wang, Yingxu; Liang, Victor; Yin, Nan; Liu, Siwei; Segal, Eran","year":2026,"journal":"Briefings in bioinformatics, 27(1)","doi":"10.1093/bib/bbag038","pmid":"41662353","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16387","title":"A novel antimicrobial peptide AH-12 attenuates mitochondrial response to inflammatory stimuli and prevents periodontitis via antibacterial and anti-inflammatory effects.","authors":"Wang, Yuanchen; Zhang, Shuting; Sun, Jinrong; Zhang, Qian; Zhang, Xi","year":2026,"journal":"Biomaterials advances, 182, 214711","doi":"10.1016/j.bioadv.2026.214711","pmid":"41544477","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"AH-12, engineered from the minimal inhibitory fragment of salivary Histatin 5 through N-terminal modification, amidation, and acetylation, demonstrated dual therapeutic activity:\n\n**Antibacterial effects:**\n- Killed Fusobacterium nucleatum, Porphyromonas gingivalis, and Streptococcus gordonii (key periodontal pathogens)\n- Worked via bacterial membrane lysis\n- Suppressed FadA adhesin secretion in F. nucleatum (reducing bacterial attachment)\n\n**Anti-inflammatory effects:**\n- Stabilized mitochondrial calcium (Ca²⁺) levels\n- Reduced mitochondrial reactive oxygen species (mtROS) overproduction\n- Prevented mitochondrial DNA (mtDNA) release\n- Attenuated inflammatory cascades driven by mitochondrial dysfunction\n\n**Delivery innovation:**\n- GelMA hydrogel (GelMA@AH-12) enabled controlled release in periodontal pockets\n- In vivo studies validated efficacy in animal periodontitis models","whyItMatters":"Periodontitis affects nearly half of adults over 30 and is linked to heart disease, diabetes, and other systemic conditions. Antibiotic resistance is making standard treatments less effective. AH-12 offers a dual-action alternative: it kills bacteria through mechanisms that are harder for microbes to develop resistance against (membrane disruption), while simultaneously reducing the inflammation that drives tissue destruction. This combination addresses both causes of gum disease damage.","specificNumbers":"","methodology":"Researchers engineered AH-12 by systematically modifying P-113, the minimal inhibitory fragment of human Histatin 5. In vitro assays tested antibacterial activity against three oral pathogens and characterized the mechanism of membrane disruption. Anti-inflammatory effects were evaluated by measuring mitochondrial function (Ca²⁺ levels, mtROS, mtDNA release) in inflammatory conditions. A GelMA hydrogel was engineered for controlled release, and in vivo efficacy was validated in animal periodontitis models.","limitations":"This is a preclinical study using in vitro assays and animal models. Translation to human periodontal therapy requires clinical trials. The hydrogel delivery system's durability and release kinetics in the complex oral environment need further optimization. Long-term safety of AH-12 in oral tissues has not been assessed. Manufacturing scale-up and cost considerations for peptide-based therapeutics may present practical challenges. The specific animal model used and its similarity to human periodontitis progression are not detailed."},{"rthcId":"RPEP-16388","title":"Cardiorenal protective effects of glucagon-like peptide-1 receptor agonists in chronic kidney disease: a systematic review and meta-analysis.","authors":"Wang, Yuqi; Feng, Luda; Wang, Yajing; Li, Boyang; Liang, Ning; Song, Xuan; Qin, Jianguo; Zhang, Mianzhi; Li, Yu","year":2026,"journal":"Renal failure, 48(1), 2620155","doi":"10.1080/0886022X.2026.2620155","pmid":"41644273","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16389","title":"Dual-targeted nano-inhibitors of pyroptosis for synergistic therapy of traumatic brain injury.","authors":"Wang, Zhao; Ma, Zhangqiang; Fu, Haijuan; Zhang, Huamiao; Zhu, Heping; Nie, Zhenyu; Huang, Leyi; Hu, Honghua; Zhou, Min; Xiao, Zhenkun; Li, Yang; Liu, HuiPing; Bi, Qiuchen; Tang, Longguang; Wang, Bing","year":2026,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 114683","doi":"10.1016/j.jconrel.2026.114683","pmid":"41765742","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16390","title":"Design and Mechanistic Study of Pf-15: A Linear Antimicrobial Peptide Derived from Gramicidin S Skeleton.","authors":"Wang, Zhengxiao; Peng, Shuting; Wang, Lantao; Lu, Zhengfeng; Wu, Qingxin; Zhang, Yan; Li, Shuanglong; Chen, Daoyuan; Qin, Xiaofei","year":2026,"journal":"Journal of agricultural and food chemistry","doi":"10.1021/acs.jafc.5c12939","pmid":"41733505","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16391","title":"Comparative efficacy and mechanism of Moringa oleifera leaves as a substitute for Rhei Radix et Rhizoma in Houpo Sanwu Decoction: A transcriptomic analysis of constipation alleviation via the PI3K-Akt pathway.","authors":"Wang, Zhihao; Yue, Xingnan; Feng, Shuyi; Li, Jiaqi; Wang, Shuo; Lan, Xuemei; Li, Caifeng; Wang, Lan; Li, Zhiyong; Yang, Bin","year":2026,"journal":"Journal of ethnopharmacology, 355(Pt B), 120517","doi":"10.1016/j.jep.2025.120517","pmid":"41067323","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16392","title":"Eucommia alleviates high fat diet-induced MASLD via the F. prausnitzii/butyrate/GPR43/GLP-1 signaling.","authors":"Wang, Zhineng; Zhu, Ying; Wang, Guohua; Sun, Mayu; Yao, Wenbo; Ba, Qian","year":2026,"journal":"Journal of ethnopharmacology, 355(Pt A), 120587","doi":"10.1016/j.jep.2025.120587","pmid":"40935212","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Eucommia bark extract (EBE) dramatically attenuated high-fat-diet-induced weight gain, oxidative stress, inflammation, lipid accumulation, and liver fibrosis in MASLD mice. The complete mechanistic chain was mapped:\n\n1. EBE selectively expanded Faecalibacterium prausnitzii (a major butyrate-producing bacterium) in the gut\n2. This increased colonic butyric acid levels\n3. Butyrate activated GPR43 receptors on enteroendocrine cells (confirmed by GPR43 knockdown abolishing the response)\n4. GPR43 activation drove GLP-1 synthesis, raising circulating GLP-1 levels\n5. GLP-1 enhanced AMPK phosphorylation in the liver via GLP-1 receptor signaling\n6. Activated AMPK suppressed lipogenesis (fat creation) and promoted lipophagy (fat breakdown)\n\nCritically, EBE did not directly trigger GLP-1 release in STC-1 cells in vitro — the effect was entirely microbiome-mediated. Fecal microbiota transplantation from EBE-treated donors recapitulated all metabolic improvements in recipient mice.","whyItMatters":"MASLD is the most common chronic liver disease worldwide with no truly effective drug treatments. This study reveals a natural way to boost the body's own GLP-1 production through gut microbiome modification — essentially achieving some of the metabolic benefits of GLP-1 drugs (like semaglutide) by stimulating the body to make more of its own GLP-1. The fecal transplant confirmation is particularly compelling, proving the gut bacteria are the key mediators.","specificNumbers":"","methodology":"C57BL/6 mice were fed a high-fat diet to induce MASLD and orally administered Eucommia bark extract throughout feeding. Metabolic parameters, liver histology, and signaling pathways were assessed. Gut microbiota composition was analyzed by 16S rRNA sequencing. In vitro experiments tested whether EBE directly stimulated GLP-1 release in STC-1 enteroendocrine cells. GPR43 knockdown confirmed the receptor's role. Fecal microbiota transplantation from EBE-treated donors to recipient mice tested whether the gut microbiome changes were sufficient to reproduce benefits.","limitations":"This is a mouse study, and the high-fat diet model may not fully replicate human MASLD. The Eucommia bark extract is a complex mixture of many compounds, and the specific active components driving the microbiome changes are not identified. Quantitative data on the degree of GLP-1 increase, weight loss, and liver improvement are not specified in the abstract. Human gut microbiome responses to the same extract may differ significantly. Long-term safety and the durability of microbiome changes after stopping treatment are unknown."},{"rthcId":"RPEP-16393","title":"Body Composition Changes After Bariatric Surgery or Treatment With GLP-1 Receptor Agonists.","authors":"Wang, Zicheng; Wang, Lei; Zhang, Xinmeng; Lowery, Brandon D; Shaffer, Lauren Lee; Chen, You; Wells, Quinn S; Flynn, Charles R; Williams, Brandon; Spann, Matthew; Srivastava, Gitanjali; Samuels, Jason M; Yu, Danxia","year":2026,"journal":"JAMA network open, 9(1), e2553323","doi":"10.1001/jamanetworkopen.2025.53323","pmid":"41511769","tags":["semaglutide","tirzepatide","body-composition"],"studyType":"observational","evidenceStrength":"high","keyFinding":"Over 24 months, both bariatric surgery and GLP-1 drugs (semaglutide/tirzepatide) produced substantial fat loss and moderate lean mass loss, but surgery was dramatically more effective. Surgery patients lost 49.7% of their fat mass versus 18.0% for GLP-1RA patients at 24 months. Lean mass loss was 11.7% with surgery versus 3.3% with GLP-1 drugs. Crucially, both groups improved their lean-to-fat ratio — meaning the weight lost was predominantly fat, not muscle. The lean-to-fat ratio improved to 2.0 with surgery and 1.5 with GLP-1 drugs at 24 months. Men preserved lean mass better than women, especially on GLP-1 drugs.","whyItMatters":"One of the biggest concerns about GLP-1 weight-loss drugs is that they cause excessive muscle loss (\"Ozempic body\"). This large real-world study provides reassuring data: while both surgery and GLP-1 drugs do cause some lean mass loss, the ratio of fat-to-lean mass lost is favorable in both cases. The lean-to-fat ratio actually improved, meaning patients became proportionally leaner. This is the largest real-world body composition comparison between bariatric surgery and modern GLP-1 drugs.","specificNumbers":"n=3,066 · Surgery: 49.7% fat loss, 11.7% FFM loss at 24mo · GLP-1RA: 18.0% fat loss, 3.3% FFM loss at 24mo · FFM:FM ratio improved in both groups · Surgery FFM:FM 2.0 vs GLP-1RA 1.5 at 24mo · Men preserved more lean mass than women","methodology":"Retrospective cohort study using electronic health records from Vanderbilt University Medical Center. 1,257 bariatric surgery patients and 1,809 GLP-1RA patients (semaglutide or tirzepatide) were followed for up to 24 months. Body composition was measured by bioelectrical impedance analysis at 2+ timepoints. Results were adjusted for age, sex, race, baseline BMI, diabetes status, treatment year, and time.","limitations":"This is a retrospective observational study, not a randomized trial — the surgery and GLP-1RA groups differed in baseline characteristics (surgery patients had higher mean BMI: 46.8 vs 41.0). Single-center data from Vanderbilt may not generalize to all populations. Bioelectrical impedance analysis is less precise than DEXA for measuring body composition. The GLP-1RA group included both semaglutide and tirzepatide, which may have different body composition effects."},{"rthcId":"RPEP-16394","title":"Harnessing meat byproducts for health: bioactive peptides to modulate gut microbiota and promote sustainability.","authors":"Waqar, Muhammad; Awlqadr, Farhang Hameed; Ullah, Qudrat; Muneer, Amna; Mushtaq, Nageen; Rafiq, Iqra; Haider, Waqas; Sajjad, Nimra; Panpipat, Worawan; Chaijan, Manat; Ageru, Temesgen Anjulo","year":2026,"journal":"Food chemistry: X, 34, 103538","doi":"10.1016/j.fochx.2026.103538","pmid":"41630887","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16395","title":"Pharmacotherapy for obesity management-Emphasizing the role of GLP-1 receptor agonist-based therapeutics.","authors":"Warden, Bruce A; Duell, Paul Barton; Bucheit, John D; Purnell, Jonathan Q","year":2026,"journal":"Journal of clinical lipidology, 20(1S), 65-96","doi":"10.1016/j.jacl.2025.11.013","pmid":"41708216","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16396","title":"Hypothalamic and sex-related hormones in migraine.","authors":"Warfvinge, Karin; Edvinsson, Jacob C A; Maddahi, Aida; Edvinsson, Lars","year":2026,"journal":"The journal of headache and pain, 27(1)","doi":"10.1186/s10194-026-02289-z","pmid":"41680623","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review reveals that estrogen has a close transcriptional relationship with calcitonin gene-related peptide (CGRP) and its receptor component RAMP1, both central targets of current migraine therapies. Falling plasma levels of estrogen, progesterone, and hypothalamic oxytocin may trigger migraine attacks, while higher levels appear protective.\n\nOxytocin receptors have recently been found to be expressed in the trigeminovascular system (TGVS), the key neural pathway in migraine. Estrogen, acting through multiple receptor subtypes, influences expression levels of both oxytocin and its receptor, creating a hormonal-peptide axis that may explain the three-fold higher migraine prevalence in women.","whyItMatters":"Understanding why migraine disproportionately affects women has been a longstanding challenge. This review connects the dots between hormonal fluctuations and the molecular pathways targeted by modern migraine drugs, potentially opening new treatment approaches — including oxytocin-based therapies — and explaining why current CGRP-targeting treatments may work differently in men and women.","specificNumbers":"","methodology":"This is a narrative review synthesizing recent data on the expression and function of sex hormones, hypothalamic hormones (oxytocin, vasopressin), and migraine-related peptides (CGRP) in neural structures relevant to migraine, including both the central nervous system and the trigeminovascular system.","limitations":"This is a narrative review, not a systematic review or meta-analysis. The underlying mechanisms linking hormone fluctuations to migraine are still not fully understood. Testosterone and vasopressin are noted as less extensively studied. The clinical applicability of oxytocin receptor findings in the trigeminovascular system has not yet been tested in therapeutic trials."},{"rthcId":"RPEP-16397","title":"Disparities in Prescription of Long-Acting GLP-1s.","authors":"Wasden, Katherine; Sheu, Nora; Medhati, Pourya; Tsai, Thomas C; Kim, Dong Wook; Tavakkoli, Ali; Apovian, Caroline M; Sheu, Eric G","year":2026,"journal":"Obesity (Silver Spring, Md.)","doi":"10.1002/oby.70152","pmid":"41771653","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16398","title":"Vitamin C Conjugates in Biomedicine: A Comprehensive Exploration with Drugs, Polymers, Proteins, and Peptides.","authors":"Wavhale, Sarika R; Shaikh, Anwar R","year":2026,"journal":"Mini reviews in medicinal chemistry","doi":"10.2174/0113895575257065251113073957","pmid":"41510717","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Vitamin C conjugation serves as a versatile 'Trojan horse' platform for drug delivery. When drugs like diclofenac, aspirin, and naproxen are linked to vitamin C, they gain improved transport across the blood-brain barrier via SVCT-mediated uptake, opening potential treatments for neurodegenerative disorders. Antiviral conjugates such as saquinavir-vitamin C show enhanced oral absorption by bypassing efflux mechanisms.\n\nPeptide-vitamin C conjugates leverage the antioxidant properties of vitamin C alongside peptide-based cellular targeting, providing synergistic benefits particularly in cosmetics and dermatology. Protein conjugates using carriers like human serum albumin (HSA) and bovine serum albumin (BSA) facilitate improved systemic transport, while nanostructure incorporation enhances oxidative stability and intracellular delivery through endocytosis.","whyItMatters":"Drug delivery remains one of the biggest challenges in medicine — many promising therapies fail because they can't reach their targets effectively. This review highlights how a simple, naturally occurring nutrient (vitamin C) can be used as a molecular 'ticket' to smuggle drugs past biological barriers. The peptide conjugation angle is especially relevant for developing next-generation cosmeceuticals and targeted dermatological treatments.","specificNumbers":"","methodology":"This is a comprehensive review article that synthesizes findings from multiple published studies on vitamin C conjugation strategies. The authors examined research across several conjugation categories: small-molecule drugs, polymers, lipids, peptides, natural compounds, proteins, and nanostructures such as gold nanoparticles.","limitations":"As a review article, this study does not present new experimental data. The effectiveness of many described conjugates has only been demonstrated in laboratory settings, and clinical translation remains limited. The review may also be subject to selection bias in the studies it chose to highlight, and long-term safety data for most vitamin C conjugates is not discussed."},{"rthcId":"RPEP-16399","title":"The Influence of GLP-1 Agonists on Human Mesenchymal Stem Cells: A Systematic Review.","authors":"Weber, Luisa; Hashemnia Sharbabaki, Maryam; Fuchs, Benedikt; Alberton, Paolo; Giunta, Riccardo; Mert, Sinan; Thierfelder, Nikolaus","year":2026,"journal":"Stem cell reviews and reports, 22(1), 26-46","doi":"10.1007/s12015-025-11002-7","pmid":"41129073","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16400","title":"A Novel Machine Learning Post-processing Filter for Mass Spectrometry-Based Proteogenomics Leveraging Retention Time Deviation and Peptide Physicochemical Properties.","authors":"Wei, Feifei; Sasada, Tetsuro","year":2026,"journal":"Methods in molecular biology (Clifton, N.J.), 2980, 251-259","doi":"10.1007/978-1-0716-4832-2_11","pmid":"41085625","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16401","title":"The insect pathogenic fungus Beauveria bassiana excretes a novel effector essential for fungal colonization within the hosts.","authors":"Wei, Kang; Ding, Jin-Li; Wang, Xue-Ting; Gao, Ben-Jie; Feng, Ming-Guang; Ying, Sheng-Hua","year":2026,"journal":"Pesticide biochemistry and physiology, 217, 106844","doi":"10.1016/j.pestbp.2025.106844","pmid":"41461411","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16402","title":"A Phase 1 Open-Label Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of a Single Intranasal Dose of Zavegepant in Healthy Chinese Adults.","authors":"Wei, Qiong; Wu, Jufang; Dai, Yangyi; Lin, Jiaye; Ge, Beikang; Sun, Yanhui; Zhang, Jing; Wang, Jing; Li, Chen; Ding, Ding; Liu, Jing; Shahin, Mohamed H","year":2026,"journal":"Clinical pharmacology in drug development, 15(1), e1617","doi":"10.1002/cpdd.1617","pmid":"41109979","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16403","title":"Probable Tirzepatide-Induced Rhabdomyolysis in an HIV-Positive Patient.","authors":"Wells, Drew A; Duncan, Kaulin; Sakaan, Sami","year":2026,"journal":"Hospital pharmacy, 00185787261426980","doi":"10.1177/00185787261426980","pmid":"41756106","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16404","title":"Pharmacomicrobiomics: Exploring the role of gut microbiota in type 2 diabetes and antidiabetic drug mechanisms.","authors":"Wen, Dingsheng; Wang, Xiangyue; He, Yanping; Hao, Xiaoqing; Huang, Weihua; Zhou, Honghao; Zhang, Wei; Li, Xiong","year":2026,"journal":"Nutrition, metabolism, and cardiovascular diseases : NMCD, 36(2), 104379","doi":"10.1016/j.numecd.2025.104379","pmid":"41152039","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16405","title":"Design and experimental verification of novel angiotensin-converting enzyme and dipeptidyl peptidase IV inhibitory peptides from Ziziphus jujuba peptide KALVAP.","authors":"Wen, Huan; Lan, Jing; Dang, Kuo; Wang, Yanli; Pan, Daodong; Gao, Xinchang; Dang, Yali","year":2026,"journal":"Journal of the science of food and agriculture, 106(1), 249-259","doi":"10.1002/jsfa.70156","pmid":"40879458","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"WALVAP demonstrated 6.25-fold higher DPP-IV inhibitory activity than the parent peptide KALVAP (IC₅₀: 360.39 vs 1,372.57 μmol/L in Caco-2 cells), while WPLVAP showed 3.52-fold improvement. Both peptides retained the ACE-inhibitory (blood pressure-lowering) activity of the original KALVAP.\n\nIn oral glucose tolerance tests in C57BL/6 mice, both WALVAP and WPLVAP significantly improved glucose metabolism by promoting secretion of insulin (11.13% and 11.61% increase), GLP-1 (11.12% and 11.61% increase), and GIP (7.58% and 7.66% increase). Molecular dynamics simulations revealed that both peptides inhibit DPP-IV primarily through interactions with key binding site residues Glu205, Trp629, Glu206, Arg125, and Arg429.","whyItMatters":"Hypertension and type 2 diabetes frequently coexist, and patients often take multiple medications for each condition. A single peptide that inhibits both ACE (lowering blood pressure) and DPP-IV (improving blood sugar) could simplify treatment. This study demonstrates that rational peptide design can convert a single-target food-derived peptide into a dual-action candidate, providing a blueprint for developing multifunctional peptide therapeutics from natural sources.","specificNumbers":"","methodology":"Starting from the jujube-derived ACE inhibitory peptide KALVAP, researchers designed nine modified peptides incorporating structural features known to enhance DPP-IV inhibition. Candidates were screened through molecular docking simulations, then validated with in vitro DPP-IV inhibition assays and Caco-2 cell experiments. The top two candidates (WALVAP and WPLVAP) were tested in vivo using oral glucose tolerance tests in C57BL/6 mice, measuring insulin, GLP-1, and GIP secretion. Molecular dynamics simulations elucidated the binding mechanism.","limitations":"The in vivo effects were tested only in normal mice with an oral glucose tolerance test, not in diabetic or hypertensive animal models where the dual activity would be most relevant. The peptides were tested acutely, and chronic effects on blood pressure and blood sugar are unknown. Oral bioavailability — critical for food-derived peptides — was not directly measured; peptides are typically degraded during digestion. The incretin increases (~11%) are modest and may not be clinically meaningful. Manufacturing feasibility for clinical use was not addressed."},{"rthcId":"RPEP-16406","title":"Pheochromocytoma crisis combined with median arcuate ligament syndrome: A rare case report.","authors":"Wen, Jiang-Xiong; Li, Wen-Jia; Guo, Jing; Siliath, Hongnaly; Xiao, Yun","year":2026,"journal":"Medicine, 105(1), e46794","doi":"10.1097/MD.0000000000046794","pmid":"41496095","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16407","title":"Endocannabinoid Modulation in Headache: Mechanisms, Models, and Translational Therapies.","authors":"Wen, Jie; Zhang, Yumin","year":2026,"journal":"Cells, 15(4)","doi":"10.3390/cells15040331","pmid":"41744774","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16408","title":"Beyond Diabetes: A Review of Emerging Indications for Glucagon-Like Peptide-1 Receptor Agonists.","authors":"West, Lucianne; Patolia, Harsh; Chapman, Brittany; Laffin, Luke; Vest, Amanda R; Sauer, Andrew J; Martyn, Trejeeve","year":2026,"journal":"Reviews in cardiovascular medicine, 27(1), 44528","doi":"10.31083/RCM44528","pmid":"41659089","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Robust clinical trial data now supports GLP-1 RA efficacy across multiple conditions beyond diabetes: significant weight loss in obesity, improved cardiovascular outcomes, preserved renal function in chronic kidney disease, and benefits in metabolic dysfunction-associated steatotic liver disease (MASLD, formerly NAFLD). Heart failure with preserved ejection fraction (HFpEF) has emerged as a particularly promising indication.\n\nAdditional trials are underway to strengthen the evidence base for these newer indications. The review also notes that innovations including oral GLP-1 formulations and combination therapies (such as dual GLP-1/GIP agonists) may expand access and improve treatment adherence.","whyItMatters":"GLP-1 receptor agonists are arguably the most impactful new drug class in medicine today. Understanding the full scope of their potential applications is essential for clinicians across multiple specialties — not just endocrinologists. This review provides a comprehensive roadmap of where the evidence stands for each emerging indication, helping guide clinical decision-making as guidelines evolve rapidly.","specificNumbers":"","methodology":"This is a narrative review synthesizing clinical trial data and emerging evidence on GLP-1 receptor agonist use across cardiometabolic diseases. The authors reviewed major clinical trials, guideline updates, and ongoing research to assess the current state and future direction of GLP-1 RA therapeutics beyond their original diabetes indication.","limitations":"As a narrative review, the paper is subject to selection bias in the studies chosen for discussion. Many of the emerging indications are still supported by a limited number of trials, and long-term outcomes data is still accumulating. The review acknowledges significant practical barriers including cost, access, and adherence that limit real-world implementation. Head-to-head comparisons between different GLP-1 RAs for non-diabetes indications are largely lacking."},{"rthcId":"RPEP-16409","title":"Dual versus monotherapy with SGLT2 inhibitor and GLP-1 receptor agonist: PRECIDENTD pragmatic randomized trial.","authors":"Wexler, Deborah J; Mayberry, Lindsay S; Nelson, Lyndsay A; Lema-Driscoll, Jeremy; Flores, Ligia C; Malloy, Maureen; MacFadyen, Jean G; Shen, Joseph; Zaharris, Elaine; Karanchi, Harsha; Chatterjee, Ranee; Benziger, Catherine P; Decker, Jake E; Kalyani, Rita; Manrique-Acevedo, Camila; Lonier, Jacqueline; Simeone, Edward; Mieras, Kathleen; Siqueira, Amanda R O; Rothman, Russell L; Jones, W Schuyler; Glynn, Robert J; Everett, Brendan M","year":2026,"journal":"American heart journal, 294, 107332","doi":"10.1016/j.ahj.2025.107332","pmid":"41456635","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16410","title":"Baseline characteristics in the SYNCHRONIZE™-2 randomized phase 3 trial of survodutide, a glucagon receptor/GLP-1 receptor dual agonist, for obesity in people with type 2 diabetes.","authors":"Wharton, Sean; le Roux, Carel W; Bozkurt, Biykem; Platz, Elke; Bleckert, Gabriele; Ajaz Hussain, Samina; Brueckmann, Martina; Startseva, Elena; Kloer, Isabel M; Kaplan, Lee M","year":2026,"journal":"Diabetes, obesity & metabolism, 28(2), 1490-1498","doi":"10.1111/dom.70263","pmid":"41216778","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16411","title":"Congenital Hyperinsulinemic Hypoglycemia With a New HADH Mutation and Pancreatic Overexpression of GLP-1 Receptors.","authors":"Widmer, Andrea; Zumsteg, Urs; Szinnai, Gabor; Filges, Isabel; Meier, Stephanie; De Geyter, Julie; Antwi, Kwadwo; Wild, Damian; Nuoffer, Jean-Marc; Christ, Emanuel","year":2026,"journal":"The Journal of clinical endocrinology and metabolism, 111(2), 358-365","doi":"10.1210/clinem/dgaf423","pmid":"40705962","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16412","title":"The Peptide Plastic Surgeon: A Review of Evidence on Regenerative Peptide Supplementation and Potential in Aesthetic Plastic Surgery.","authors":"Wiegmann, Aaron L; Trovato, Matthew J; González, Pedro; Chadab, Tara M; Rohrich, Rod J","year":2026,"journal":"Aesthetic surgery journal","doi":"10.1093/asj/sjag020","pmid":"41572734","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16413","title":"Survivin recombinant overlapping peptide (ROP) vaccine in advanced solid tumours: a first-in-human, multicentre, open-label, phase 1a dose-escalation study.","authors":"Wijaya, Wynne; Morris, Thomas; Forster, Martin D; Flynn, Michael; Tuthill, Mark; Thistlethwaite, Fiona; Williams, Anja; Finch, William; Lu, Wenshu; Jiang, Shisong","year":2026,"journal":"EClinicalMedicine, 91, 103717","doi":"10.1016/j.eclinm.2025.103717","pmid":"41536940","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16414","title":"Semaphorin 7A regulates axon outgrowth in subcutaneous white adipose tissue.","authors":"Willows, Jake W; Lazor, Lindsey M; Wandling, Gabriela; Butke, William; Fenesha, Fatma; Corps, Kara N; Peters, Sarah B; Townsend, Kristy L","year":2026,"journal":"Molecular metabolism, 105, 102329","doi":"10.1016/j.molmet.2026.102329","pmid":"41654014","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16415","title":"Semaglutide and tirzepatide effects on cardiovascular outcomes in people with overweight or obesity in the real world (STEER).","authors":"Wilson, Lauren; Zhao, Zhenxiang; Divino, Victoria; Bassan, Matthew; Hartaigh, Bríain Ó; Stensen, Signe; Ozer, Kerem","year":2026,"journal":"Diabetes, obesity & metabolism, 28(3), 2403-2415","doi":"10.1111/dom.70436","pmid":"41491349","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16416","title":"Distinct and complementary metabolic effects of GLP-1 and glucagon receptor agonism in diet-induced obese mice.","authors":"Winther-Sørensen, Marie; Rasmussen, Christine; Trammell, Samuel A J; Hansen, Caroline; Vyberg, Mogens; Serizawa, Reza; Richter, Erik A; Grevengoed, Trisha J; Gluud, Lise Lotte; Kuhre, Rune E; Wewer Albrechtsen, Nicolai J","year":2026,"journal":"Peptides, 195, 171462","doi":"10.1016/j.peptides.2025.171462","pmid":"41429191","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16417","title":"Reduced-Frequency GLP1 Therapy Maintains Weight, Body Composition, and Metabolic Syndrome Improvements: A Case Series.","authors":"Wong, Michelle; Wu, Ash; Garhe, Pawanjot K; Biermann, Mitch","year":2026,"journal":"Obesity (Silver Spring, Md.)","doi":"10.1002/oby.70137","pmid":"41732031","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16418","title":"Investigating the functional connectivity between central glucagon-like peptide-1 (GLP-1) and glutamatergic signaling: a systematic review.","authors":"Wong, Sabrina; Le, Gia Han; Teopiz, Kayla; McIntyre, Roger S","year":2026,"journal":"CNS spectrums, 31(1), e4","doi":"10.1017/S1092852926100844","pmid":"41607204","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 31 preclinical and pharmacologic studies, GLP-1 receptor agonists were consistently associated with increased glutamate release, activation of NMDA and AMPA receptors, and enhanced release of neurotrophic factors linked to neurogenesis, neurodifferentiation, and synaptic plasticity. Crucially, the food intake suppression caused by GLP-1 RAs was found to be dependent on AMPA receptor signaling but not NMDA receptor signaling, suggesting a specific mechanistic pathway for the anti-obesity effects of these drugs.","whyItMatters":"GLP-1 receptor agonists like semaglutide are among the most prescribed drugs worldwide for obesity and diabetes. Understanding exactly how they work in the brain — particularly their interaction with glutamate, which accounts for 90% of excitatory neurotransmission — could open doors to new neuropsychiatric applications and help explain both their therapeutic benefits and potential side effects.","specificNumbers":"","methodology":"The researchers conducted a systematic review of studies published across PubMed, Ovid, and Scopus databases from inception through March 2025. Two independent reviewers screened studies using the Covidence platform. They included in vitro, in vivo, and pharmacologic studies, ultimately identifying 31 studies that met eligibility criteria. No human clinical studies were found.","limitations":"No human clinical studies were available for inclusion, so all findings come from preclinical (animal and cell-based) research. Results from animal models don't always translate directly to humans. The review also did not assess the quality or risk of bias of included studies in detail, and publication bias toward positive results may influence the overall picture."},{"rthcId":"RPEP-16419","title":"Meta-analysis of clinically available pharmacotherapy of biopsy confirmed metabolic dysfunction associated steatohepatitis (MASH).","authors":"Wood, Emily; Akande, Rukayat; Iqbal, Iqra; Albert, Stewart G","year":2026,"journal":"Diabetes, obesity & metabolism, 28(2), 1266-1277","doi":"10.1111/dom.70314","pmid":"41365848","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16420","title":"Antimicrobial Peptides in Preventive Medicine: Current Perspectives on Coating Strategies.","authors":"Wouters, Milan; Van Moll, Laurence; Derin, Emine; Van Looy, Sara; De Vooght, Linda; Delputte, Peter; Cos, Paul","year":2026,"journal":"ACS infectious diseases","doi":"10.1021/acsinfecdis.5c01050","pmid":"41733083","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review finds that AMP-based surface coatings for medical devices have progressed from simple surface immobilization techniques to sophisticated matrix-based systems that offer improved stability, biocompatibility, and controlled release of antimicrobial activity. AMPs are particularly suited for this application due to their broad-spectrum antimicrobial activity and structural versatility.\n\nHowever, despite extensive in vitro and small-scale in vivo studies demonstrating efficacy against biofilm formation on devices like endotracheal tubes, catheters, and implants, clinical translation remains very limited. Key barriers include regulatory ambiguity around peptide-coated devices and high production costs.","whyItMatters":"Device-associated infections are a major cause of hospital-acquired illness and death, and antibiotic-resistant biofilms on medical devices are extremely difficult to treat once established. Prevention through antimicrobial coatings could be far more effective than treating established infections, and AMPs offer a promising alternative as conventional antibiotics lose effectiveness.","specificNumbers":"","methodology":"This is a comprehensive narrative review of the current literature on antimicrobial peptide-based coating strategies for medical devices. The authors surveyed published research on various coating approaches, device types, and the progression from basic surface immobilization to advanced matrix-based delivery systems.","limitations":"Most evidence comes from in vitro studies and small-scale animal models, with very limited clinical trial data. The review notes significant translation barriers including unclear regulatory pathways for peptide-coated devices and high manufacturing costs that may limit commercial viability. Long-term stability of peptide coatings in the body and potential for resistance development remain open questions."},{"rthcId":"RPEP-16421","title":"Incretin Signaling Neighborhoods and Adverse Drug Reactions.","authors":"Wright, Shane C; Lindquist, Peter; Rosenkilde, Mette M; Lauschke, Volker M","year":2026,"journal":"Annual review of pharmacology and toxicology, 66(1), 501-518","doi":"10.1146/annurev-pharmtox-062124-015046","pmid":"40929510","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16422","title":"Effect of Wall-Material Assembly Sequence on Ovalbumin-Chitosan Nanoparticles for Antarctic Krill Peptide Delivery.","authors":"Wu, Hao; Wen, Kun; Xie, Jing; Xue, Bin; Bian, Xiaojun; Sun, Tao","year":2026,"journal":"Foods (Basel, Switzerland), 15(4)","doi":"10.3390/foods15040786","pmid":"41750979","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16423","title":"Risk of perioperative cardiorespiratory complications and mortality associated with preoperative glucagon-like peptide-1 receptor agonist use in type 2 diabetes mellitus: a nationwide propensity-score matched study.","authors":"Wu, Hsiang-Ling; Chen, Jui-Tai; Cata, Juan Pablo; Hsieh, Chia-Hsing; Cherng, Yih-Giun; Tai, Ying-Hsuan","year":2026,"journal":"British journal of anaesthesia, 136(1), 86-97","doi":"10.1016/j.bja.2025.08.003","pmid":"40940281","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16424","title":"Tirzepatide versus SGLT2 inhibitors for MASLD: a multi-institutional propensity score-matched cohort study.","authors":"Wu, Jheng-Yan; Lin, Yu-Min; Hsu, Wan-Hsuan; Liu, Ting-Hui; Tsai, Ya-Wen; Huang, Po-Yu; Chuang, Min-Hsiang; Yu, Tsung; Lai, Chih-Cheng","year":2026,"journal":"Hepatology international","doi":"10.1007/s12072-025-11021-z","pmid":"41535629","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"After 1:1 propensity score matching of 23,106 patients per group from the TriNetX global network:\n\nTirzepatide vs SGLT2 inhibitors in MASLD:\n- Primary composite (mortality + MACE + MALO): HR 0.72 (95% CI: 0.63-0.83) — 28% reduction\n- All-cause mortality: HR 0.55 (95% CI: 0.43-0.71) — 45% reduction\n- Major adverse cardiovascular events: HR 0.68 (95% CI: 0.58-0.80) — 32% reduction\n- Major adverse liver outcomes: HR 0.66 (95% CI: 0.54-0.80) — 34% reduction\n\nAll associations were consistent across subgroups stratified by age, sex, BMI, and comorbidities, demonstrating robust benefit.","whyItMatters":"MASLD affects roughly 30% of the global population and is the fastest-growing cause of liver transplantation. No drug was specifically approved for MASLD until very recently, and clinicians must choose between several options. This is the first large head-to-head comparison showing tirzepatide is superior to SGLT2 inhibitors — one of the other leading treatment candidates — for hard clinical outcomes including death and liver failure progression. The magnitude of benefit (45% mortality reduction) is striking.","specificNumbers":"","methodology":"Retrospective multi-institutional cohort study using the TriNetX global research network. Adults ≥18 with MASLD newly initiated on tirzepatide or SGLT2 inhibitors between January 2022 and June 2025 were included. 1:1 propensity score matching balanced baseline characteristics. Cox proportional hazards models estimated hazard ratios for the composite primary outcome and individual components. Subgroup analyses assessed consistency across demographics and comorbidities.","limitations":"Observational retrospective design — cannot establish causation despite propensity matching. The TriNetX database may have coding inaccuracies and ascertainment bias. Tirzepatide was approved more recently than SGLT2 inhibitors, so follow-up duration may differ. Indication bias is possible — sicker patients might be more likely to receive one drug over the other. The 45% mortality reduction is very large for an observational study and should be interpreted cautiously. Randomized controlled trials are needed for definitive comparison."},{"rthcId":"RPEP-16425","title":"The impact of nutrition, exercise, and pharmacotherapy on menstrual health in adolescents with overweight and obesity.","authors":"Wu, Julius; Jacobson-Dickman, Elka","year":2026,"journal":"Nutrition (Burbank, Los Angeles County, Calif.), 143, 113021","doi":"10.1016/j.nut.2025.113021","pmid":"41386097","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16426","title":"Magnetic continuum robot-mediated intracranial delivery of peptide nanophotosensitizers for glioblastoma photodynamic therapy.","authors":"Wu, Junfeng; Li, Na; Ma, Tianyang; Lin, Daojing; Zhou, Junjian; Song, Yingqiu; Cheng, Wen; Wu, Anhua; Jiao, Niandong","year":2026,"journal":"Biomaterials advances, 178, 214458","doi":"10.1016/j.bioadv.2025.214458","pmid":"40834586","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16427","title":"Inhibition of human Nav1.4 by D-amino acid modified μ-CnIIIC.","authors":"Wu, Renfei; Wang, Zhuying; Quan, Yuan; He, Zhen; Zhao, Yingsheng; Wang, Yaya; Wang, Junmei; Ma, Zhenghai","year":2026,"journal":"Bioorganic chemistry, 170, 109484","doi":"10.1016/j.bioorg.2026.109484","pmid":"41520619","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16428","title":"Serum IgG Response to a Conserved Domain of Commensal Flagellins Predicts Future Risk of Crohn's Disease in First-degree Relatives.","authors":"Wu, Richard Y; Xue, Mingyue; Zhao, Qing; Jeong, Sean; Griffiths, Anne M; Dieleman, Levinus A; Steinhart, A Hillary; Aumais, Guy; Bressler, Brian; Panaccione, Remo; Deslandres, Colette; Mack, David R; Bernstein, Charles N; Marshall, John K; Turner, Dan; Xu, Wei; Duck, Lennard W; Elson, Charles O; Turpin, Williams; Lee, Sun-Ho; Croitoru, Kenneth","year":2026,"journal":"Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association","doi":"10.1016/j.cgh.2025.12.006","pmid":"41534761","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16429","title":"Bioactive peptides-incorporated photo-crosslinking hydrogel for suture-free repair of corneal injuries.","authors":"Wu, Wei; Huai, Shuo; Li, Chenhao; Wang, Haiqi; Zhang, Wenyi; Liu, Xiaoying; Yang, Ying; Zou, Yunxiao; Lei, Lei; Qu, Jia; Li, Xingyi; Wang, Jiaqing","year":2026,"journal":"Journal of colloid and interface science, 708, 139869","doi":"10.1016/j.jcis.2026.139869","pmid":"41538991","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16430","title":"Clinical Utility of Continuous Non-contact Cardiac Function Monitoring via Fiber-Optic Micro-Vibration Sensing System-based Myocardial Performance Index in Heart Failure Patients with Reduced Ejection Fraction.","authors":"Wu, Xiaoyan; Zhan, Jing; Li, Chenze; Fu, Xuelei; Zhang, Chao; Zhao, Tao; Chen, Kewei; Katsnelson, Michael; Li, Zhengying; Lu, Zhibing","year":2026,"journal":"Cardiology, 1-28","doi":"10.1159/000551488","pmid":"41838810","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16431","title":"Calcitonin gene-related peptide/protein kinase A: A novel pathway to regulate patency of ductus arteriosus.","authors":"Wu, Yen-Hsien; Liu, Yi-Ching; Jan, Ren-Long; Tsai, Siao-Ping; Huang, Shang-En; Wu, Bin-Nan; Lo, Shih-Hsing; Chen, I-Chen; Dai, Zen-Kong; Wu, Jiunn-Ren; Tseng, Yu-Hsin; Yeh, Jwu-Lai; Hsu, Jong-Hau","year":2026,"journal":"Biochemical pharmacology, 248, 117840","doi":"10.1016/j.bcp.2026.117840","pmid":"41724283","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16432","title":"Distinct contribution of spinal neuropeptide Y and NPY1R neurons to morphine analgesia.","authors":"Wu, Yifei; Chen, Yiming; Zeng, Qian; Xu, Kangtai; Li, Yitong; Yang, Haoyi; Yang, Saiyang; Liu, Yaqi; Wu, Jiawei; Ji, Luyao; Ma, Qiming; Wang, Zilong","year":2026,"journal":"Brain : a journal of neurology","doi":"10.1093/brain/awag077","pmid":"41738433","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16433","title":"Efficacy and safety of anti-prediabetic drugs in patients with prediabetes: a Bayesian network meta-analysis.","authors":"Wu, Yike; Wang, Zihan; Tuersun, Adili; Yu, Qiuxia; Zhong, Yu; Ali, Shah Syed Alfakhar; Liu, Haiyang; Hu, Xinyi; Zhang, Yanfei; Pang, Liyuan; Li, Longzhou; Gao, Long; Wu, Qiwen; Wang, Shan; Cui, Meng; Sun, Linglu; Wu, Yulin; Yin, Antong; Zhang, Lei; Ma, Guo","year":2026,"journal":"BMC medicine","doi":"10.1186/s12916-026-04705-2","pmid":"41715123","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16434","title":"Fever enhances host bacterial defence while limiting mitochondrial damage.","authors":"Wu, Yonghan; Rowe, Elijah; Siryaporn, Albert; Gross, Steven P","year":2026,"journal":"Research square","doi":"10.21203/rs.3.rs-8724408/v1","pmid":"41674812","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16435","title":"Degradation Products of Guangdong Finger Citron Water-Soluble Polysaccharides by Gut Microbiota Ameliorate Type 2 Diabetes Mellitus via the Cyclic Adenosine Monophosphate Pathway.","authors":"Wu, Yuxiao; Zhong, Cheng; Liu, Heming; Wu, Zhiqin; Zhou, Aimei","year":2026,"journal":"Journal of food science, 91(2), e70924","doi":"10.1111/1750-3841.70924","pmid":"41655054","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16436","title":"The role of neprilysin in musculoskeletal diseases.","authors":"Wu, Zuping; Wang, Ying; Wu, Na; Lu, Mingcheng; Shi, Jiejun","year":2026,"journal":"Tissue & cell, 99, 103324","doi":"10.1016/j.tice.2026.103324","pmid":"41529369","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies several key roles for neprilysin in musculoskeletal health. NEP degrades pro-inflammatory neuropeptides like substance P, reducing local inflammation in joints and muscles. It also breaks down endogenous opioids, playing a role in pain regulation.\n\nIn stem cell research, NEP promotes osteogenic (bone), chondrogenic (cartilage), and myogenic (muscle) differentiation of mesenchymal stem cells. The NEP inhibitor sacubitril promotes cartilage growth plate thickening and bone growth in animal models of chondrodysplasia, while NEP activators — rather than inhibitors — promote muscle growth in castrated rats. This tissue-specific directional difference is an important finding.","whyItMatters":"Neprilysin is already a drug target in cardiology — sacubitril/valsartan (Entresto) is widely prescribed for heart failure. This review highlights that the same enzyme has important but underappreciated roles in bones, cartilage, and muscles. Understanding these effects matters because millions of patients taking NEP-targeting heart drugs may experience musculoskeletal effects, and these drugs could potentially be repurposed for orthopedic conditions.","specificNumbers":"","methodology":"This is a narrative review paper that synthesizes findings from preclinical animal studies, cell culture experiments, and clinical observations about neprilysin's role in musculoskeletal biology and disease. No new experiments were conducted.","limitations":"As a narrative review, this paper does not include new experimental data or a systematic search methodology. Most evidence discussed comes from animal models and cell culture, with limited human clinical data for musculoskeletal applications specifically. The review does not include meta-analysis or quality assessment of the cited studies."},{"rthcId":"RPEP-16437","title":"Complete radiologic and clinical reversal of lumbar spinal epidural lipomatosis via GLP-1 agonist.","authors":"Wurm, Lennard M; Koch, Peter; Ertel, Wolfgang; Laue, Dominik","year":2026,"journal":"Journal of surgical case reports, 2026(2), rjag052","doi":"10.1093/jscr/rjag052","pmid":"41694436","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A 48-year-old man with morbid obesity (153 kg), extensive spinal epidural lipomatosis, and critical lumbar stenosis underwent a non-surgical treatment strategy:\n\n- Semaglutide initiated for GLP-1-mediated weight loss\n- Medical cannabis for non-opioid pain control\n- Over 1 year follow-up: weight decreased from 153 kg to 93.8 kg (59.2 kg loss)\n- MRI demonstrated near-complete regression of epidural fat\n- Resolution of spinal stenosis\n- Major improvement in pain and mobility\n- Patient remained neurologically intact\n- Surgery was successfully avoided\n- Reported as the first documented case of SEL reversal through medical weight loss alone","whyItMatters":"Spinal epidural lipomatosis typically requires surgical decompression, which carries risks and recovery time. This case demonstrates that GLP-1-mediated weight loss can completely reverse this condition, potentially offering a non-surgical alternative. As semaglutide is already widely available, this approach could change the management algorithm for obesity-related spinal conditions.","specificNumbers":"","methodology":"This is a single-patient case report documenting a non-surgical treatment approach for spinal epidural lipomatosis. The patient received semaglutide for weight loss and medical cannabis for pain management. Clinical outcomes were assessed through weight monitoring, pain and mobility evaluations, neurological examinations, and serial MRI imaging over one year of follow-up.","limitations":"This is a single case report and cannot establish generalizability. The contribution of semaglutide versus weight loss alone versus medical cannabis to the improvement cannot be separated. The long-term durability of the fat regression is unknown, particularly if weight is regained after stopping semaglutide. Not all patients with SEL may respond similarly, especially those whose condition is caused by corticosteroids rather than obesity."},{"rthcId":"RPEP-16438","title":"Discovery of Two Novel Scorpion Venom Peptides Activating TRPML2 to Impair ZIKV Internalization.","authors":"Xia, Zhiqiang; Yang, Xuhua; He, Dangui; Chang, Jiayuan; Xie, Lixia; Liu, Qian; Jin, Jiahuan; Li, Bing; Tashima, Alexandre K; Kwok, Hang Fai; Cao, Zhijian","year":2026,"journal":"Toxins, 18(2)","doi":"10.3390/toxins18020110","pmid":"41745776","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16439","title":"Expression of Calcitonin Gene-related Peptide and Its Application to Cochlear Implantation Under Local Anesthesia With Monitored Anesthesia Care in the Very Elderly: The University of California, Los Angeles, Experience.","authors":"Xiao, Adam Y; Trieu, Christine T; Li, Linda; Harvey, Michelle L; Fu, Qianjie; Lopez, Ivan A; Ishiyama, Gail; Ishiyama, Akira","year":2026,"journal":"Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology","doi":"10.1097/MAO.0000000000004810","pmid":"41557455","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16440","title":"Regulation of virulence factors of Pseudomonas aeruginosa by Scutellaria baicalensis, Prunella vulgaris and antimicrobial peptide LL-37.","authors":"Xiao, Qian; Du, Kaiwen; Luo, Li; Luo, Yanfen; Wu, Xinggui; Zhao, Chanjing; Zeng, Jianming; Huang, Wen; Chen, Cha","year":2026,"journal":"Journal of medical microbiology, 75(2)","doi":"10.1099/jmm.0.002122","pmid":"41637127","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16441","title":"Semaglutide attenuates diabetic vascular calcification by enhancing autophagy and lysosomal function via targeting CPNE1.","authors":"Xiao, Shengjue; Li, Wei; Liu, Naifeng","year":2026,"journal":"Apoptosis : an international journal on programmed cell death, 31(3)","doi":"10.1007/s10495-026-02269-3","pmid":"41793524","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16442","title":"Novel defensin-like antimicrobial peptides as promising targets for the control of Bactrocera dorsalis.","authors":"Xie, Bingqin; Ye, Chao; Zuo, Panfei; Lin, Zhangbiao; Yi, Junchen; Song, Bo; Wang, Jinjun; Dou, Wei","year":2026,"journal":"Pest management science","doi":"10.1002/ps.70588","pmid":"41603168","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16443","title":"Endogenous Glucagon-Like Peptide 1 Enhanced by Vildagliptin Reduces Triglyceride Appearance During Intraduodenal Fat Infusion in Type 2 Diabetes.","authors":"Xie, Cong; White, Jake B; Huang, Weikun; Horowitz, Michael; Rayner, Christopher K; Verjans, Johan W; Snel, Marten F; Psaltis, Peter J; Wu, Tongzhi","year":2026,"journal":"Diabetes","doi":"10.2337/db25-0980","pmid":"41591292","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Vildagliptin (a DPP-4 inhibitor that preserves endogenous GLP-1) selectively reduced two triglyceride species — TG(54:4) and TG(54:5) — during intraduodenal fat infusion (each P < 0.01), without significantly affecting total triglycerides.\n\nCritically, when endogenous GLP-1 signaling was blocked with exendin(9-39) during vildagliptin treatment, plasma total triglycerides increased significantly (P < 0.001), along with elevations in 10 individual triglyceride species (P < 0.05 each). This reversal upon GLP-1 blockade provides direct evidence that endogenous GLP-1 contributes to physiological regulation of postprandial triglyceride appearance in type 2 diabetes.","whyItMatters":"While GLP-1 receptor agonist drugs (like semaglutide) are known to improve lipid profiles, it wasn't clear whether the body's own GLP-1 does the same thing. This study proves it does — endogenous GLP-1 actively helps control blood fat levels after eating. This matters because it suggests that even modest increases in natural GLP-1 (through diet, DPP-4 inhibitors, or other means) could provide meaningful lipid-lowering benefits, and it deepens our understanding of why GLP-1 drugs reduce cardiovascular risk.","specificNumbers":"","methodology":"Fifteen participants with type 2 diabetes (managed by diet and/or metformin) were studied in a double-blind, randomized, crossover design across three visits. Vildagliptin (50 mg) or placebo was given orally 60 minutes before fat infusion. On one vildagliptin day, the GLP-1 receptor blocker exendin(9-39) was infused intravenously. A lipid emulsion was infused directly into the duodenum (2 kcal/min for 120 minutes), followed by a mixed meal. Plasma triglycerides were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS) for detailed individual species analysis.","limitations":"Small sample size (n=15) limits generalizability. Only participants with diet/metformin-managed T2D were studied — results may differ in more advanced diabetes or with insulin therapy. The study used intraduodenal lipid infusion rather than normal eating, which doesn't fully replicate physiological meal ingestion. The study measured acute postprandial effects; chronic lipid-lowering effects of enhanced GLP-1 were not assessed. Only vildagliptin was tested, so results may not apply to all DPP-4 inhibitors equally."},{"rthcId":"RPEP-16444","title":"A gut-liver lipid flux checkpoint mediates FAHFA protection from MASLD.","authors":"Xie, Hao; Cheng, Hong Sheng; Ng, Jia Xun Jarryl; Zhang, Shuang; Kim, Joseph Han Sol; Tan, Soon Heng; Tan, Choon-Hong; Tan, Nguan Soon","year":2026,"journal":"Pharmacological research, 224, 108085","doi":"10.1016/j.phrs.2025.108085","pmid":"41485679","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16445","title":"Semaglutide Versus Dulaglutide and Liraglutide in Chinese Patients With T2DM: A Multicenter Real-World Study.","authors":"Xie, Zeyu; Gan, Bin; Cao, Weiling; Liu, Jiang; Chen, Jisheng","year":2026,"journal":"Obesity (Silver Spring, Md.), 34(1), 101-113","doi":"10.1002/oby.70065","pmid":"41266832","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16446","title":"pH Modulation as a Key Strategy for Developing a Stable Lyotropic Liquid Crystal Formulation of Octreotide Acetate.","authors":"Xin, Yingshun; Yang, Shupei; Li, Chan; Chang, Yaya; Luo, Meiling; Yan, Ying; Liu, Jia; Liu, Yulin; Wang, Yajuan; Li, Chunlei","year":2026,"journal":"Pharmaceutics, 18(2)","doi":"10.3390/pharmaceutics18020239","pmid":"41754980","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16447","title":"Diabetic ketoacidosis induced by liraglutide overdose for weight loss in a type 2 diabetes patient: A case report.","authors":"Xu, Hekai; Zhang, Yuqin","year":2026,"journal":"Medicine, 105(4), e46197","doi":"10.1097/MD.0000000000046197","pmid":"41578502","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"A cumulative liraglutide dose of 18 mg over 3 days (10x the recommended maximum of 1.8 mg/day) induced severe DKA with pH 6.9, markedly elevated β-hydroxybutyrate, and hyperkalemia. Conventional DKA management (IV fluids, insulin, electrolyte correction) failed to correct the profound acidosis. Salvage hemodialysis was required and rapidly stabilized metabolic parameters. This represents one of the most severe documented cases of GLP-1 receptor agonist overdose-induced DKA.","whyItMatters":"As GLP-1 drugs gain popularity for weight loss, the risk of misuse — patients self-dosing beyond prescriptions to accelerate results — is a growing concern. This case demonstrates that GLP-1 overdose can cause life-threatening metabolic emergencies even in type 2 diabetes patients, who are typically at low risk for DKA. Clinicians prescribing these drugs need to explicitly counsel patients about the dangers of dose escalation and the risk of DKA.","specificNumbers":"","methodology":"Single case report of a 43-year-old female with type 2 diabetes mellitus who self-administered a massive liraglutide overdose. Clinical course, laboratory values, treatment approach, and outcome are documented.","limitations":"This is a single case report and cannot establish the frequency or predictability of DKA from liraglutide overdose. The patient's underlying diabetes and metabolic status may have contributed to her vulnerability. The mechanism by which liraglutide overdose triggers DKA in a type 2 diabetes patient (typically protected from DKA by residual insulin secretion) is not fully explained. Case reports cannot determine dose-response relationships for adverse events."},{"rthcId":"RPEP-16448","title":"Cathelicidin CATH-2 suppresses the NF-κB/ROS/NLRP3 signaling pathway via regulating mTOR-dependent autophagy during Streptococcus suis infection.","authors":"Xu, Liuyi; Lu, Yilin; Xu, Shichao; Liu, Yuqian; Liu, Hongdou; Zhang, Tingting; Pan, Yandi; Lu, Yi; Wang, Zhouyuan; Cao, Xuefeng; Li, Zhiwei; Fang, Rendong; Peng, Lianci","year":2026,"journal":"Veterinary research, 57(1), 32","doi":"10.1186/s13567-025-01694-7","pmid":"41578407","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16449","title":"Identifying cardiac safety signals of disproportionate reporting for CGRP antagonists: evidence from the FDA Adverse Event Reporting System.","authors":"Xu, Shuaimin; Song, Weijuan; Wang, Yanhong; Zhao, Yang","year":2026,"journal":"Naunyn-Schmiedeberg's archives of pharmacology","doi":"10.1007/s00210-026-05116-z","pmid":"41706150","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16450","title":"Molecular evidence associating GLP-1 receptor agonists and brain-derived neurotrophic factors in neurodegenerative and psychiatric disorders: A systematic review.","authors":"Xu, Tianyi; Zheng, Yang Jing; Wong, Sabrina; Dri, Christine E; Zhou, Xin Tong; Teopiz, Kayla M; Le, Gia Han; McIntyre, Roger S","year":2026,"journal":"Asian journal of psychiatry, 117, 104870","doi":"10.1016/j.ajp.2026.104870","pmid":"41619567","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16451","title":"Migraine-induced cochlear injury triggers ZBP1-mediated PANoptosis via CGRP signaling.","authors":"Xu, Wandi; Zhai, Ni; Chen, Jingyu; Zhou, Shun; Tian, E; Guo, Zhaoqi; Zhou, Zhanghong; Yu, Xixi; Zhai, Ziyu; Zhang, Xin; Wang, Yixu; Ma, Xin; Lu, Yisheng; Zhang, Sulin","year":2026,"journal":"The journal of headache and pain, 27(1)","doi":"10.1186/s10194-026-02286-2","pmid":"41629775","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16452","title":"Electroacupuncture ameliorates chronic heart failure: the role of CRH neurons in the paraventricularnucleus of the hypothalamus.","authors":"Xu, Wenyuan; Guo, Yujie; Wang, Jiaying; Zhao, Xianghu; Cai, Lian; Ren, Zhihao; Cui, Shuai; Wu, Haosheng; Xu, Nenggui; Wu, Shengbing; Zhou, Meiqi","year":2026,"journal":"Frontiers in neuroscience, 20, 1741523","doi":"10.3389/fnins.2026.1741523","pmid":"41821869","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16453","title":"Development and validation of nomogram for predicting neurogenic pulmonary edema in hypertensive intracerebral hemorrhage.","authors":"Xu, Yajuan; Shi, Yinxian","year":2026,"journal":"Frontiers in cardiovascular medicine, 13, 1726478","doi":"10.3389/fcvm.2026.1726478","pmid":"41710358","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16454","title":"Engineered Biomimetic Nanorobots Orchestrate Targeted Nose-to-Brain Delivery to Resolve Neuron-Glia Entanglement against Parkinson's Disease.","authors":"Xu, Yang; Zhao, Jing-Yu; Xu, Xi-Yuan; Liu, Yu-Da; Li, Yu-Wen; Peng, Li-Hua","year":2026,"journal":"Small (Weinheim an der Bergstrasse, Germany), e13394","doi":"10.1002/smll.202513394","pmid":"41607240","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16455","title":"Risk of Heart Failure Hospitalization for GLP-1 Receptor Agonists Versus DPP-4 Inhibitors or SGLT-2 Inhibitors in Patients With Type 2 Diabetes: A Target Trial Emulation.","authors":"Xu, Yang; Huang, Tao; Zhang, Yue; Ji, Dongze; Tuttle, Katherine R; Carrero, Juan-Jesus; Fu, Edouard L","year":2026,"journal":"Circulation","doi":"10.1161/CIRCULATIONAHA.125.075157","pmid":"41732861","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16456","title":"A screening platform in Escherichia coli for modified antimicrobial peptide by combining surface display and co-culture.","authors":"Xu, Yanli; Kuipers, Oscar P","year":2026,"journal":"Microbiological research, 307, 128484","doi":"10.1016/j.micres.2026.128484","pmid":"41759311","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The researchers successfully combined E. coli surface display with co-culture techniques to produce intracellularly modified RiPPs (ribosomally synthesized and post-translationally modified peptides) extracellularly. A brevicidine-mimicking mutant peptide was modified intracellularly by two enzymes — OspR (introducing ornithine residues) and SyncM (introducing a methyllanthionine ring) — then displayed on the E. coli surface using Lpp-OmpA and Omp1 proteins.\n\nIn a co-culture with separate E. coli cells displaying the leader peptidase LahT150 (via the ice nucleating protein InaK), the modified peptide was successfully cleaved and detected in the culture supernatant, where its antimicrobial activity was confirmed. Surface display efficiency exceeded 90% using the Lpp-OmpA and Omp1 systems.","whyItMatters":"Finding new antibiotics is urgent but difficult, especially for complex modified peptides that can't be easily screened through traditional genetic libraries. This platform bridges a key gap: it allows gene-encoded production and modification of peptides that mimic non-ribosomal peptide structures — previously very difficult to screen at scale. With over 90% display efficiency and proven antimicrobial activity detection, it could significantly speed up the discovery of next-generation peptide antibiotics.","specificNumbers":"","methodology":"The platform used two populations of E. coli in co-culture. The first population expressed a precursor peptide that was modified intracellularly by RiPP-modifying enzymes (OspR for ornithine incorporation, SyncM for methyllanthionine ring formation) and then displayed on the cell surface via Lpp-OmpA or Omp1 fusion proteins. The second population displayed the leader peptidase LahT150 on its surface via the InaK ice nucleating protein. When co-cultured, the peptidase cleaved the displayed modified peptide, releasing it into the supernatant for activity testing. Display efficiency was quantified using flow cytometry or related surface detection methods.","limitations":"The study demonstrated proof-of-concept with a single brevicidine-mimicking peptide variant. Scalability to large mutant libraries has not been shown. The antimicrobial activity assessment was basic — detailed MIC values against diverse pathogens were not reported in the abstract. The co-culture system's performance may vary with different peptide sizes and modification types. Industrial-scale application feasibility remains to be determined."},{"rthcId":"RPEP-16457","title":"Innovative Molecules and Delivery Technologies Enabling the Future of GLP-1-based Therapies.","authors":"Xu, Yining; Drucker, Daniel J; Traverso, Giovanni; Beloqui, Ana","year":2026,"journal":"Endocrine reviews, 47(1), 1-23","doi":"10.1210/endrev/bnaf027","pmid":"40755395","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review identifies several technology platforms poised to reshape GLP-1-based therapy delivery:\n\n1. **Oral small-molecule agonists** — non-peptide compounds that activate GLP-1 receptors and can be taken as pills, avoiding injections entirely\n2. **Ultralong-acting injectable technologies** — formulations designed to extend dosing intervals far beyond the current once-weekly standard\n3. **Continuous-acting implantable pumps** — devices that deliver GLP-1 drugs steadily without patient intervention\n4. **Smart-acting electronic devices** — technology-enabled delivery systems that can adjust dosing\n5. **Nutrient-induced cell therapies** — engineered cells that produce GLP-1 in response to food intake, mimicking natural physiology\n6. **Noninvasive delivery systems** — alternative routes that bypass needles entirely\n\nEach approach addresses different patient needs and clinical challenges, from needle phobia to treatment adherence.","whyItMatters":"Hundreds of millions of people worldwide could benefit from GLP-1 therapies, but many are deterred by injectable administration, high costs, or the commitment to weekly dosing. The delivery technologies reviewed here could dramatically expand access by making treatment as simple as taking a daily pill, wearing a patch, or receiving a one-time implant. Solving the delivery challenge is arguably as important as the drug discovery itself for maximizing public health impact.","specificNumbers":"","methodology":"This is a comprehensive narrative review published in Endocrine Reviews. The authors surveyed the current clinical development pipeline and preclinical research landscape for GLP-1-based therapies, categorizing innovations by delivery technology type and assessing their current development stage, challenges, and potential for clinical translation.","limitations":"As a review article, this paper synthesizes existing research rather than presenting new data. Many of the technologies discussed are in early preclinical stages and may not reach clinical use. The review may not capture all proprietary technologies under development by pharmaceutical companies. Real-world feasibility, cost comparisons, and patient preference data for these emerging approaches are largely unavailable."},{"rthcId":"RPEP-16458","title":"Defensin1, an IMD pathway antiviral peptide, inhibits rice gall dwarf virus propagation in leafhoppers.","authors":"Xu, Yuanyuan; Du, Yu; Xu, Mengjia; Wang, Jia; Jia, Dongsheng; Wei, Taiyun; Li, You","year":2026,"journal":"Pest management science","doi":"10.1002/ps.70587","pmid":"41631569","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16459","title":"Low-Power Short-Pulse-Width Fractional Microneedle Radiofrequency Relieves LL37-Induced Rosacea-Like Skin Inflammation.","authors":"Xu, Zhiyi; Shen, Siqi; Zhao, Jingting; Wang, Jing; Wang, Xinlan; Gu, Li; Zhou, Shu; Zhao, Jing; Gu, Liqun; Chen, Lin; Zhou, Bingrong; Hua, Hui","year":2026,"journal":"Journal of cosmetic dermatology, 25(2), e70727","doi":"10.1111/jocd.70727","pmid":"41664378","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16460","title":"FGF2-Based Cyclic Peptide PET Tracer for Noninvasive Detection of FGFR1 Expression in Non-Small Cell Lung Cancer.","authors":"Xue, Yan; Huang, Zhihong; Zhu, Xue; Wang, Shuang; Jiao, Yang; Wang, Xun; Tang, Jie; Xu, Dong; Zhang, Yongchang; Wang, Qian; Xu, Chunwei; Fang, Jing; Wang, Ke","year":2026,"journal":"Journal of medicinal chemistry, 69(4), 4755-4770","doi":"10.1021/acs.jmedchem.5c03417","pmid":"41700010","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16461","title":"Glucagon-like peptide-1 medicines and cancer.","authors":"Yabut, Julian M; Drucker, Daniel J","year":2026,"journal":"Nature cancer, 7(2), 260-271","doi":"10.1038/s43018-025-01110-1","pmid":"41545715","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16462","title":"Evaluating the effects of fish protein hydrolysates on Pseudomonas aeruginosa growth and exotoxin A expression.","authors":"Yaghoubzadeh, Zahra; Ghiasi, Maryam","year":2026,"journal":"Biotechnology letters, 48(2), 34","doi":"10.1007/s10529-026-03708-6","pmid":"41665730","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16463","title":"Benefits of glucagon-like peptide (GLP)-1 receptor agonists on 5-year risk of major amputation, all-cause mortality, myocardial infarction, and ischemic stroke in patients with chronic limb-threatening ischemia.","authors":"Yahyavi, Ashkan; Zokaei Nikoo, Maedeh; Hussein, Leen; Katara, Aarti; Perez, Jaime A; Shishehbor, Mehdi H","year":2026,"journal":"Vascular medicine (London, England), 31(1), 47-53","doi":"10.1177/1358863X251393107","pmid":"41410071","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 139,173 diabetic patients with chronic limb-threatening ischemia (CLTI), GLP-1 receptor agonist users had significantly lower 5-year rates of major amputation (HR 0.745, 95% CI 0.679–0.816), all-cause mortality, and myocardial infarction compared to non-users after propensity score matching (15,743 patients per group). The reduction in ischemic stroke did not reach statistical significance (p=0.353). These benefits persisted after adjusting for demographics, comorbidities, concurrent medications, and laboratory values.","whyItMatters":"Chronic limb-threatening ischemia is the most severe form of peripheral artery disease and carries devastating consequences — amputation, heart attack, and death. This is among the first large studies to show that GLP-1 receptor agonists may protect these high-risk patients from limb loss and cardiovascular events, suggesting benefits that extend far beyond blood sugar control.","specificNumbers":"n=139,173 total · 17,306 GLP-1RA users · 15,743 matched per group · 91% match rate · major amputation HR 0.745 · mean age 65.4 · 58.9% male · mean follow-up 753.7 days","methodology":"Retrospective cohort study using the TriNetX real-world clinical data platform. Patients with type 2 diabetes and CLTI were identified and categorized by GLP-1RA prescription. Propensity score matching balanced groups on demographics, comorbidities, medications, and lab values (91% match rate, 15,743 per group). Cox proportional hazards models, Kaplan-Meier curves, and log-rank tests assessed 5-year outcomes.","limitations":"Retrospective observational design cannot prove causation. Despite propensity matching, residual confounding from unmeasured variables is possible. GLP-1RA users may have had better access to care or adherence behaviors. The abstract contains incomplete hazard ratio data for some outcomes (all-cause mortality and MI values appear truncated). Stroke benefit was not statistically significant."},{"rthcId":"RPEP-16464","title":"Atrial to brain natriuretic peptide ratio as a marker of atrial remodeling severity and post-ablation recurrence risk in atrial fibrillation patients with left atrial enlargement.","authors":"Yamada, Shinya; Kaneshiro, Takashi; Nodera, Minoru; Amami, Kazuaki; Murota, Sadahiro; Oikawa, Masayoshi; Ishida, Takafumi; Takeishi, Yasuchika","year":2026,"journal":"Journal of interventional cardiac electrophysiology : an international journal of arrhythmias and pacing, 69(1), 125-134","doi":"10.1007/s10840-025-02157-x","pmid":"41082133","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16465","title":"Effects of vasoactive intestinal peptide on neuroexcitability of female-specific subpopulation of myelinated Ah-type neurons isolated from trigeminal ganglia of adult female rats.","authors":"Yan, Feng; Zhong-Xuan, Pan; Li-Li, Tan; Luo, Fang; Hai-Ying, Ding","year":2026,"journal":"Neuropeptides, 115, 102569","doi":"10.1016/j.npep.2025.102569","pmid":"41270459","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"In isolated female rat trigeminal ganglion Ah-type neurons:\n\n- VIP (100 nM) significantly increased firing frequency of repetitive discharge\n- VIP narrowed action potentials and increased down-stroke velocity\n- VIP deepened after-hyperpolarization (AHP)\n- AP and repolarization changes were reversed by Iberiotoxin (BK channel blocker), except AHP which was abolished by Apamin (SK channel blocker)\n- All VIP-mediated increases in firing frequency and repolarization changes were completely blocked by PG97-269 (VPAC1 antagonist)\n- PG-99-465 (VPAC2 antagonist) had no effect\n- PG97-269 alone slightly but significantly reduced baseline firing\n- Conclusion: VIP excites female-specific Ah-type neurons via VPAC1, which also plays a minor role in basal neuroexcitation","whyItMatters":"Migraine affects about 1 billion people worldwide, with women affected 3 times more than men. Understanding why requires identifying sex-specific neural mechanisms. This study reveals that VIP activates a female-specific neuron subtype in the trigeminal system through VPAC1, providing a molecular explanation for sex-based differences in migraine susceptibility and potentially a new drug target.","specificNumbers":"","methodology":"Trigeminal ganglion neurons were isolated from adult female rats. Myelinated Ah-type neurons were identified and action potentials were recorded before and after VIP treatment using whole-cell patch-clamp technique. VPAC1 (PG97-269) and VPAC2 (PG-99-465) receptor antagonists, Iberiotoxin (BK channel blocker), and Apamin (SK channel blocker) were used to dissect the signaling mechanisms.","limitations":"This was an in vitro electrophysiology study using isolated rat neurons, which may not fully represent human trigeminal physiology. The Ah-type neuron is characterized as female-specific in rats, but this finding needs validation in human tissue. VIP's role in the complex migraine pathophysiology involves multiple cell types and brain regions not captured in isolated neuron recordings. The concentrations used (100 nM) may not reflect physiological VIP levels during migraine attacks."},{"rthcId":"RPEP-16466","title":"Enhanced antifouling performance of ultra-thin antimicrobial peptide membrane through chemical-crosslinking layer-by-layer assembly.","authors":"Yan, Jiaying; Wang, Panpan; Zhu, Jinlong; Zhou, Xiaoqun; Wang, Han; Qiu, Shiyi; Su, Zilin; Zhang, Zhilin; Hu, Yu; Ma, Jun","year":2026,"journal":"Water research, 291, 125171","doi":"10.1016/j.watres.2025.125171","pmid":"41418612","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16467","title":"Discovery of novel, high-affinity HBV T-cell epitopes by molecular dynamics-augmented proteome-wide screening.","authors":"Yan, Mingchen; Jin, Meiling; Xia, Wei; Sun, Jing; Zhong, Zhihao; Wan, Guoyue; Wang, Jian; Huang, Jian-Dong; Zhang, John Z H","year":2026,"journal":"Protein science : a publication of the Protein Society, 35(3), e70503","doi":"10.1002/pro.70503","pmid":"41711273","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16468","title":"From Bioactive Peptides to Transdermal Peptides: An Emerging Strategy for Revolutionizing Drug Delivery.","authors":"Yang, Guangpu; Li, Yixuan; Tian, Jingwen; Ding, Wenxiu; Li, Xiuxiu; Ma, Xuanxuan; Wei, Tao; Xu, Jing","year":2026,"journal":"Macromolecular bioscience, 26(1), e00485","doi":"10.1002/mabi.202500485","pmid":"41531394","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16469","title":"The novel B-cell epitope peptide vaccine, MAX449, exhibits significant anti-tumor efficacy and enhances the therapeutic effects of PD-1 antibodies on tumors by modulating the activity of PMN-MDSCs.","authors":"Yang, Hong; Han, Xiao; Deng, Boshao; Zhao, Yunpei; Zhao, Jing; Wu, Yufei; Liu, Guokang; Zeng, Shiyu; Wang, Siyi; Shen, Zhejuan; Wang, Lulu; Sun, Zihan; Lu, Wenping; Wu, Yuzhang; Chen, Jian","year":2026,"journal":"Theranostics, 16(7), 3771-3789","doi":"10.7150/thno.122439","pmid":"41608565","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16470","title":"The Antimicrobial Peptide CRAMP-34 Eradicates Escherichia coli Biofilms by Interfering with the kduD-Dependent Network.","authors":"Yang, Hongzao; Xiong, Jing; Su, Sisi; Yang, Zhuo; Yang, Wu; Peng, Lianci; Zhang, Suhui; Qiu, Jinjie; He, Yuzhang; Chen, Hongwei","year":2026,"journal":"Antibiotics (Basel, Switzerland), 15(1)","doi":"10.3390/antibiotics15010083","pmid":"41594121","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16471","title":"Anatomical evidence links the stomach to the central amygdala, a region responsive to local GLP-1R agonist induced feeding and nausea-like behaviors in male mice.","authors":"Yang, Hui; Yu, Wenxiang; Gao, Yunling; Wang, Jie; Xu, Shaoyong","year":2026,"journal":"Frontiers in endocrinology, 17, 1740052","doi":"10.3389/fendo.2026.1740052","pmid":"41685252","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16472","title":"Impact of newer antihyperglycemic agents on hepatic complications: A systematic review and meta-analysis of data from 5.3 million patients with type 2 diabetes mellitus.","authors":"Yang, Jiwon; Hwang, Yeongseok; Ju, Jin-Sung; Han, Seungbong; An, Jihyun; Shim, Ju Hyun","year":2026,"journal":"Hepatology (Baltimore, Md.)","doi":"10.1097/HEP.0000000000001695","pmid":"41609749","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 receptor agonists were associated with a 23% reduction in hepatocellular carcinoma (HCC) risk (HR 0.77, 95% CI 0.66–0.90) and a 21% reduction in non-HCC liver-related events (HR 0.79, 95% CI 0.65–0.95) compared to other glucose-lowering therapies.\n\nSGLT-2 inhibitors showed similar liver protection: 24% reduction in HCC (HR 0.76, 95% CI 0.67–0.86) and 18% reduction in liver-related events (HR 0.82, 95% CI 0.73–0.92).\n\nDPP-4 inhibitors showed no protection against HCC (HR 1.12, 95% CI 0.91–1.39) and were associated with a 24% increased risk of liver-related events (HR 1.24, 95% CI 1.15–1.34).\n\nIn patients with chronic liver disease specifically, GLP-1 receptor agonists were uniquely associated with reduced hepatic decompensation (HR 0.79, 95% CI 0.71–0.88).","whyItMatters":"Liver cancer is the sixth most common cancer and the third leading cause of cancer death globally, and type 2 diabetes significantly increases the risk. This study provides the most comprehensive evidence to date that the choice of diabetes medication matters for liver health. For the millions of diabetic patients also at risk for liver disease, GLP-1 receptor agonists may offer dual protection — managing blood sugar while reducing liver cancer and liver disease risk.","specificNumbers":"","methodology":"Systematic literature search identified studies reporting hepatic complications in type 2 diabetes patients prescribed GLP-1 RAs, SGLT-2 inhibitors, or DPP-4 inhibitors, compared against other glucose-lowering therapies. From 2,228 records screened, 36 cohort studies comprising 5,363,858 patients were included. Random-effects meta-analyses estimated pooled hazard ratios. Subgroup analyses were conducted for patients with chronic liver disease.","limitations":"All 36 included studies were observational cohort studies, not randomized controlled trials, so confounding cannot be fully excluded. The comparator groups varied across studies (different glucose-lowering therapies), which introduces heterogeneity. The analysis could not account for disease duration, medication adherence, or specific drug doses within each class. The DPP-4 inhibitor finding of increased liver-related events may reflect confounding by indication rather than a causal effect."},{"rthcId":"RPEP-16473","title":"Identification of transiently produced IgG linear epitopes in Senecavirus A for differentiating infected from vaccinated animals.","authors":"Yang, Lan; Meng, Fandan; Zhou, Hanrong; Ma, Hongwei; An, Tongqing; Jiang, Ning; Wang, Haiwei; Cai, Xuehui","year":2026,"journal":"Veterinary microbiology, 312, 110789","doi":"10.1016/j.vetmic.2025.110789","pmid":"41218398","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16474","title":"Mast cell-expressed Mrgprb2/MRGPRX2 mediates gout pain and inflammation via a neuroimmune axis.","authors":"Yang, Lin; Liu, Chengxi; Xiao, Jin; Song, Yu; Chen, Huan; Li, Dan; Zou, Cong; Hong, Tao; Liu, Yinglan; Qi, Dake; Limjunyawong, Nathachit; Liu, Wenjie; Qu, Lintao","year":2026,"journal":"JCI insight, 11(2)","doi":"10.1172/jci.insight.201781","pmid":"41574611","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16475","title":"Hypothalamic RASA1/Ras/AKT/GnRH axis reprogramming mediates GLP-1RA's central rescue of PCOS HPG dysfunction.","authors":"Yang, Linlin; Guo, Na; Wang, Xing; Zhang, Xincheng; He, Jinhong; Li, Hongyun; Zhou, Huanhuan; Ma, Huijuan","year":2026,"journal":"Diabetes, obesity & metabolism, 28(1), 711-727","doi":"10.1111/dom.70256","pmid":"41208497","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16476","title":"Lactobacillus acidophilus exerts neuroprotective effects in MPTP mice: potential links to the gut microbiota and GLP-1.","authors":"Yang, Liujing; Guo, Tongtong; Wei, Yubin; Zhang, Zheng; Sun, Yan; Yan, Ning; Ding, Songtao; Jiang, Lin; Liu, Handeng","year":2026,"journal":"Physiology & behavior, 307, 115229","doi":"10.1016/j.physbeh.2026.115229","pmid":"41539638","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16477","title":"The m6A writers PmMETTL3 and PmWTAP boost antiviral innate immunity by regulating the JAK/STAT pathway and antimicrobial peptides production in the black tiger shrimp Penaeus monodon infected with white spot syndrome virus.","authors":"Yang, Miao; Jiang, Yue; Lei, Yiguo; Wan, Boquan; Ao, Chunmei; Wang, Wei","year":2026,"journal":"International journal of biological macromolecules, 336, 149339","doi":"10.1016/j.ijbiomac.2025.149339","pmid":"41317756","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16478","title":"Antibacterial properties and mechanisms of anti-lipopolysaccharide factor 1 from Procambarus clarkii.","authors":"Yang, Qing; Du, Zhengyan; Yang, Lin; Jia, Yujing; Wang, Xinru; Li, Hao; Hou, Libo; Zhu, Lei; Kong, Xianghui","year":2026,"journal":"Fish & shellfish immunology, 169, 111051","doi":"10.1016/j.fsi.2025.111051","pmid":"41338477","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16479","title":"Glucagon-like peptide-1 receptor (GLP-1R) agonists prevent tributyltin-induced muscle atrophy/wasting via restoring GLP-1R signaling in vitro and in mice.","authors":"Yang, Rong-Sen; Lin, Yuan-Cheng; Lan, Kuo-Cheng; Wang, Ching-Chia; Tzeng, Huei-Ping; Chang, Ting-Yu; Chan, Ding-Cheng; Liu, Shing-Hwa","year":2026,"journal":"Ecotoxicology and environmental safety, 309, 119523","doi":"10.1016/j.ecoenv.2025.119523","pmid":"41352264","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16480","title":"Peptide FK2 attenuates inflammation and pro-fibrotic cellular transitions via targeting the IKKβ/NF-κB/TGF-β1 axis in renal fibrosis.","authors":"Yang, Runling; Feng, Xiaocui; Zhang, Jianfeng; Chen, Tianyi; Wang, Wenqian; Liu, Yangrui; Chen, Wanru; Bai, Jingya; Zhang, Bangzhi","year":2026,"journal":"European journal of pharmacology, 1015, 178567","doi":"10.1016/j.ejphar.2026.178567","pmid":"41565196","tags":["anti-inflammatory-peptides","kidney-disease"],"studyType":"animal-and-cell","evidenceStrength":"preliminary","keyFinding":"FK2, a 9-amino-acid peptide derived from the silk of corn (Zea mays L.), was shown to inhibit renal fibrosis both in living mice and in cell cultures. The researchers identified IKKβ as the direct molecular target of FK2. By binding to IKKβ, FK2 simultaneously blocks two major signaling pathways — IKKβ/NF-κB (which drives inflammation) and TGF-β1/Smad2/3 (which drives tissue scarring).\n\nThis dual suppression reduced the inflammatory response and inhibited two key processes that contribute to kidney scarring: macrophage-to-myofibroblast transition (MMT), where immune cells transform into scar-producing cells, and epithelial-mesenchymal transition (EMT), where kidney lining cells lose their normal identity and become fibrotic.","whyItMatters":"Chronic kidney disease affects hundreds of millions of people worldwide, and renal fibrosis — the progressive scarring of kidney tissue — is the final common pathway that leads to kidney failure. Currently, there are no effective treatments that directly halt or reverse kidney fibrosis. FK2 is notable because it targets IKKβ to simultaneously suppress both inflammation and fibrotic cell transitions, addressing two intertwined drivers of the disease with a single molecule. As a naturally derived peptide, it also represents a promising starting point for developing new anti-fibrotic drugs.","specificNumbers":"9-amino-acid peptide · derived from corn silk (Zea mays L.) · targets IKKβ directly · suppresses NF-κB and TGF-β1/Smad2/3 pathways · inhibits MMT and EMT","methodology":"The researchers used a combination of in vivo (mouse model) and in vitro (cell culture) experiments. They tested FK2 in C57BL mice with induced kidney fibrosis and in RAW 264.7 macrophage cell lines. Molecular target identification confirmed IKKβ as a direct binding partner of FK2. Pathway analysis examined the IKKβ/NF-κB and TGF-β1/Smad2/3 signaling axes to establish the mechanism of action.","limitations":"This study was conducted in mice and cell cultures, not in humans, so it remains unknown whether FK2 would be safe and effective in people. The abstract does not report specific dosing, pharmacokinetics, or long-term safety data. The mouse model of induced kidney fibrosis may not fully replicate the complexity of chronic kidney disease in humans."},{"rthcId":"RPEP-16481","title":"Antiviral activity of curcumin against Israeli acute paralysis virus in Apis mellifera: Screening and mechanistic study.","authors":"Yang, Shangning; Huang, Zhichu; Wei, Ruike; Liu, Dandan; Su, Xiaoling; Zheng, Huoqing","year":2026,"journal":"Journal of invertebrate pathology, 214, 108483","doi":"10.1016/j.jip.2025.108483","pmid":"41161636","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16482","title":"Structural basis of the VapBC5 complex from Mycobacterium abscessus and its role in regulating persister cell formation.","authors":"Yang, Sheng; Zheng, Shuping; Feng, Zhihua; Lin, Miaofang; Liu, Min; Chiang, Zu-Chian; Chen, Qi","year":2026,"journal":"International journal of biological macromolecules, 349, 150860","doi":"10.1016/j.ijbiomac.2026.150860","pmid":"41690349","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The VapBC5 crystal structure was solved at 2.24 Å resolution, revealing a heterotetrameric 2:2 assembly. The antitoxin VapB5 suppresses the toxin VapC5 through an extensive network of hydrogen bonds and salt bridges.\n\nFunctional studies showed VapC5 promotes antibiotic-tolerant survival under fluoroquinolone stress (persister cell formation), while VapB5 counteracts this phenotype. Antitoxin-derived peptides were designed, screened in E. coli, and a selected peptide was validated in M. abscessus where it attenuated VapC5-associated persistence-related phenotypes. Structure-guided mutagenesis confirmed that multiple antitoxin-toxin contacts must be disrupted to unmask VapC5 activity.","whyItMatters":"M. abscessus infections are extremely difficult to treat, often requiring months of multiple antibiotics with cure rates below 50%. Persister cells that tolerate antibiotics are a major reason treatments fail. Instead of developing new antibiotics, this study proposes a radically different approach: using peptides to disable the bacteria's persistence machinery, making existing antibiotics more effective. If this strategy works clinically, it could transform treatment of mycobacterial infections and potentially other persistent bacterial infections.","specificNumbers":"","methodology":"The VapBC5 complex was coexpressed, purified, and crystallized for X-ray structure determination at 2.24 Å resolution. Structure-guided mutagenesis identified key interface residues. Functional assays in E. coli measured antibiotic-tolerant survival under fluoroquinolone stress. Antitoxin-derived peptides were first screened in E. coli, then a selected candidate was tested in a laboratory M. abscessus strain for its ability to attenuate persistence-related phenotypes.","limitations":"The peptide was tested in laboratory strains, not clinical isolates, which may have different persistence mechanisms. Validation in M. abscessus was limited compared to the more extensive E. coli work. Drug-like properties of the peptide (stability, cell penetration, toxicity, in vivo efficacy) were not assessed. The contribution of VapBC5 to clinical persistence versus other persistence mechanisms in M. abscessus is not fully established. Translation from in vitro proof-of-concept to therapeutic application requires significant additional development."},{"rthcId":"RPEP-16483","title":"Discovery and mechanistic insights into ACE inhibitory peptides from the gastrointestinal digest of royal jelly proteins: peptidomics, bioactivity profiling, in silico screening, and in vitro validation.","authors":"Yang, Wanyu; Hu, Xiaodi; Zhang, Tianrong; Zhao, Ming; Li, Qiongmin; Sang, Mengnan; Fan, Jinling; Zhao, Yuan; Zhang, Bin","year":2026,"journal":"Food research international (Ottawa, Ont.), 229, 118476","doi":"10.1016/j.foodres.2026.118476","pmid":"41763798","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"From 1,983 peptides identified in the gastrointestinal digest of royal jelly proteins, 237 had high predicted bioactivity scores (≥0.8). After further screening, 49 soluble candidates were selected, and ACE inhibition was the most commonly predicted function.\n\nMolecular docking showed all 49 peptides bound ACE more strongly (-6.9 to -10.9 kcal/mol) than the positive control captopril (-5.6 kcal/mol). In vitro testing confirmed two top performers: FRYR (IC50 = 608 μmol/L, mixed-type inhibitor) and FFRNR (IC50 = 684 μmol/L, competitive inhibitor). FRYR's superior potency was explained by its unique ability to coordinate with the zinc catalytic center of ACE — the same site that pharmaceutical ACE inhibitors target.","whyItMatters":"Royal jelly is already a popular health food supplement, and demonstrating that its proteins release ACE-inhibiting peptides during normal digestion adds scientific backing to potential cardiovascular benefits. The study is also notable for its systematic methodology — combining peptidomics with computational screening — which represents a modern, efficient approach to discovering food-derived bioactive peptides that could be applied to any protein source.","specificNumbers":"","methodology":"Royal jelly proteins were subjected to simulated gastrointestinal digestion. The resulting peptides were identified using LC-MS/MS peptidomics. Computational screening (PeptideRanker, molecular docking, bioavailability prediction) narrowed candidates from 1,983 to 49. The top candidates were validated with in vitro ACE inhibition assays, enzyme kinetics analysis (Lineweaver-Burk plots), and detailed molecular docking to characterize binding mechanisms.","limitations":"This is an in vitro and in silico study only — no animal or human testing was performed. The IC50 values (608-684 μmol/L) are relatively high compared to pharmaceutical ACE inhibitors and even compared to some other food-derived peptides. Simulated digestion may not perfectly replicate in vivo conditions. It's unclear whether these peptides would be absorbed intact into the bloodstream at active concentrations. The strong molecular docking scores didn't translate proportionally to in vitro potency, highlighting limitations of computational predictions."},{"rthcId":"RPEP-16484","title":"The Scorpion Peptide Derivative HP-H1K8 is a Promising Topical Agent Against Methicillin-Resistant Staphylococcus Aureus.","authors":"Yang, Xuhua; Yang, Jingyu; Cao, Zhijian; Li, Zhongjie","year":2026,"journal":"Probiotics and antimicrobial proteins","doi":"10.1007/s12602-026-10951-w","pmid":"41686422","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16485","title":"Acupuncture ameliorates diet-induced obesity via the vagal-GLP-1-ARC circuit: neural mechanism of anorexigenic action.","authors":"Yang, Yanan; Shao, Yuwei; Tian, Jun; Wang, Yuezhu; Zhu, Ye; Pan, Siying; Wei, Xiali; Jiang, Linyan; Wang, Xiaoke; Shu, Qing","year":2026,"journal":"Chinese medicine, 21(1), 20","doi":"10.1186/s13020-025-01274-z","pmid":"41508004","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16486","title":"Comparative effectiveness and safety of novel antidiabetic agents in the management of obstructive sleep apnea: a systematic review, meta-analysis, and network meta-analysis.","authors":"Yang, Ying-Tian; Hou, Xin-Zheng; Zhang, Xi-Rui; Zhang, Zhen-Peng; Wang, Shi-Han","year":2026,"journal":"Respiratory medicine, 253, 108671","doi":"10.1016/j.rmed.2026.108671","pmid":"41616874","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16487","title":"Effect of bariatric surgery and pharmacological treatments on cardiovascular risk factors for adults with overweight and obesity: a systematic review and network meta-analysis.","authors":"Yang, You; Cheng, Xiaohong; Chen, Siming; Xie, Jiatong; Chen, Gowen; Li, Lifa; Feng, Yue; Chen, Yi; Liu, Guanqun; Yin, Yuan; Zhou, Tong; Zhao, Rui","year":2026,"journal":"International journal of surgery (London, England)","doi":"10.1097/JS9.0000000000004566","pmid":"41738616","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16488","title":"Receptor binding domain-independent pancoronavirus vaccine design by fusion of conserved T/B Epitopes.","authors":"Yang, Yunru; Chen, Yetian; Hong, Mengyu; Zou, Ronghua; Yao, Jingxue; Li, Entao; Wang, Jiayi; Ye, Xiaodong; Xing, Yixiang; Tang, Yangming; Lu, Xiaojie; Ding, Chengchao; He, Hongliang; Tong, Dali; Shang, Yuhua; Wang, Jian; Zhao, Guangyu; Huang, Xiaoxue; Feng, Fuli; Cheng, Qingyu; Li, Bofeng; Huang, Baoying; Tan, Wenjie; Chiu, Sandra; Jin, Tengchuan","year":2026,"journal":"Emerging microbes & infections, 15(1), 2631206","doi":"10.1080/22221751.2026.2631206","pmid":"41672103","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16489","title":"Brain-peripheral proteome crosstalk in Alzheimer's disease with and without diabetes mellitus.","authors":"Yaskolka Meir, Anat; Wang, Xingyan; Tasaki, Shinya; Sarsani, Vishal; Buchman, Aron S; Arnold, Steven E; Bennett, David A; Petyuk, Vladislav A; Liang, Liming; Capuano, Ana W; Arvanitakis, Zoe","year":2026,"journal":"Alzheimer's & dementia : the journal of the Alzheimer's Association, 22(1), e70959","doi":"10.1002/alz.70959","pmid":"41536252","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16490","title":"Glucagon-like Peptide-1 Receptor Agonists and Risk of Major Adverse Cardiovascular Events in Patients With CKD.","authors":"Yau, Kevin; Ray, Joel G; Jeyakumar, Nivethika; Luo, Bin; Abdullah, Sheikh; Dixon, Stephanie N; Wing, Sara; Clemens, Kristin K; Castrillon-Ramirez, Fabio; Udell, Jacob A; Meraz-Munoz, Alejandro; Young, Ann; Harel, Ziv; Perl, Jeffrey; Leiter, Lawrence A; Garg, Amit X; Cherney, David Z I; Wald, Ron","year":2026,"journal":"American journal of kidney diseases : the official journal of the National Kidney Foundation, 87(2), 211-229.e1","doi":"10.1053/j.ajkd.2025.09.010","pmid":"41238166","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1 receptor agonist users had a significantly lower rate of major adverse cardiovascular events (MACE) compared to DPP-4 inhibitor users: 31.6 vs. 36.5 per 1,000 person-years (SHR 0.88, 95% CI 0.80–0.97). The cardiovascular death reduction was particularly striking: SHR 0.72 (95% CI 0.62–0.85), representing a 28% lower rate. There was no effect modification by CKD stage, albuminuria level, or concurrent SGLT2 inhibitor use — meaning the cardiovascular benefit was consistent regardless of kidney disease severity or other cardioprotective medications.","whyItMatters":"CKD patients were largely excluded from the landmark cardiovascular outcome trials that established GLP-1 drugs' heart benefits. This study fills a critical evidence gap by demonstrating that the cardiovascular protection extends across the full spectrum of kidney disease in real-world practice. For clinicians managing CKD patients with diabetes, this provides strong support for choosing GLP-1 drugs over DPP-4 inhibitors when cardiovascular risk reduction is a priority.","specificNumbers":"","methodology":"Population-based retrospective cohort study using administrative health data from Ontario, Canada. Included 24,576 new GLP-1 RA users and 44,367 new DPP-4 inhibitor users with eGFR measurements, of whom 41% had CKD stages 3-5. Inverse probability of treatment weighting with propensity scores minimized confounding. Multivariable Fine-Gray subdistribution hazard models, stratified by eGFR subgroup, evaluated the primary composite MACE outcome.","limitations":"This is a retrospective observational study, so it cannot establish causation — only association. There was substantial missing albuminuria data. The comparison group (DPP-4 inhibitors) is an active comparator, not placebo, so the absolute cardiovascular benefit may differ from that estimated against no treatment. Selection bias may persist despite propensity score weighting. The study population was from Ontario, Canada, which may limit generalizability to other healthcare systems."},{"rthcId":"RPEP-16491","title":"Effects of Glucagon-Like Peptide-1 Receptor Agonist on Bone Metabolism and the Expression of Insulin Receptor Substrate 1 in an Osteoporotic Rat Model.","authors":"Ye, Yao; He, Yu-Ling; He, Jie; Yang, Dan-Yong; Xia, Ning","year":2026,"journal":"International journal of endocrinology, 2026, 4418640","doi":"10.1155/ije/4418640","pmid":"41788539","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16492","title":"GLP-1 Receptor Agonists Plus Progestins and Endometrial Cancer Risk in Nonmalignant Uterine Diseases.","authors":"Yen, Ting-Tai; Hsieh, Tina Yi Jin; Lee, Gin-Yi; Toy, Eugene P; Wei, James Cheng-Chung; Tanner, Edward J","year":2026,"journal":"JAMA network open, 9(2), e2558205","doi":"10.1001/jamanetworkopen.2025.58205","pmid":"41665904","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16493","title":"Comparative effectiveness of sleeve gastrectomy and semaglutide for weight loss and metabolic outcomes: a prospective non-randomized study.","authors":"Yen, Yutung; Zhang, Qian; Yin, Shiyi; Pu, Yujie; Song, Ke; Song, Xiaohai; Shen, Xiaoding; Wan, Qianyi; Zhao, Rui; Zhang, Guixiang; Cheng, Zhong; Widjaja, Jason; Chen, Haiyang; Chen, Yi","year":2026,"journal":"BMC medicine, 24(1), 103","doi":"10.1186/s12916-026-04648-8","pmid":"41572274","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16494","title":"Efficacy and safety of glucagon-like peptide 1 receptor agonists across all health outcomes in type 2 diabetes: An umbrella review and evidence map of randomised controlled trials.","authors":"Yeo, Dongjin; Jo, Yeona; Jeong, Jinyoung; Jeong, Yi Deun; Woo, Ho Geol; Son, Yejun; Kim, Sunyoung; Rhee, Sang Youl; Yon, Dong Keon","year":2026,"journal":"Diabetes, obesity & metabolism, 28(2), 1136-1149","doi":"10.1111/dom.70298","pmid":"41255131","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16495","title":"Urinary Antimicrobial Peptides and Cytokines as Biomarkers for Recurrent Urinary Tract Infection in Children and Adolescents.","authors":"Yepes, Guillermo; Tang, Hancong Chloe; Holdsworth, Natalie; Salamon, Kristin; Schwartz, Laura; Ching, Christina; Rust, Steve; Spencer, John David","year":2026,"journal":"medRxiv : the preprint server for health sciences","doi":"10.64898/2025.12.29.25343150","pmid":"41607650","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16496","title":"Subcellular interactions of neuropeptide Y and corticotropin-releasing factor in the central nucleus of the amygdala in the mouse.","authors":"Yerraguntla, Himavarsha; Onyekachi, Joy; Nichtova, Zuzana; Giacometti, Laura L; Goldberg, Samuel L; Barson, Jessica R; Barker, Jacqueline M; Reyes, Beverly A S","year":2026,"journal":"Neuroscience, 600, 163-173","doi":"10.1016/j.neuroscience.2026.02.026","pmid":"41720390","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16497","title":"Heterotrophic fermentation of a robust human defensin in Chlamydomonas reinhardtii provides a stable and potent antibacterial.","authors":"Yi, Jiayan; Zhang, Ji; Chen, Xiaoping; Liu, Siyuan; Qiu, Yaxuan; Meng, Xiangrui; Li, Can; Hu, Zhangfeng; Wang, Weihua; Feng, Li","year":2026,"journal":"Microbial cell factories, 25(1), 35","doi":"10.1186/s12934-025-02916-5","pmid":"41486159","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16498","title":"Next-generation therapeutics for diabetic kidney disease.","authors":"Yi, Tae Won; Sridhar, Vikas S; Scott, Jennifer; Nardone, Massimo; Cherney, David","year":2026,"journal":"Nature reviews. Nephrology","doi":"10.1038/s41581-025-01042-0","pmid":"41526484","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16499","title":"Cholecystectomy with jejunoileal bypass ameliorates diabetic metabolism in mice with type 2 diabetes through modulation of FXR and TGR5 signaling.","authors":"Yin, Haixin; Chen, Weijie; He, Xiaodong; Zeng, JianPing","year":2026,"journal":"Metabolism open, 29, 100437","doi":"10.1016/j.metop.2025.100437","pmid":"41550263","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16500","title":"Polydopamine-coated 3D electrospun sponge conjugated with thrombin receptor-activating peptide and antibacterial peptide for hemostasis and accelerated healing of infected wounds.","authors":"Yin, Shanqing; Zhou, Chengkai; Zhang, Chenxi; Zhang, Ye; Li, Zhao; Cui, Dapeng; Sun, Zhongshuai; Guo, Wei; Pan, JiaDong; Li, Fang; Li, Ming; Wang, Xin","year":2026,"journal":"Biomaterials advances, 180, 214543","doi":"10.1016/j.bioadv.2025.214543","pmid":"41106119","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16501","title":"Dynamic Coordination Hydrogel with Simultaneous Anti-infected and Angiogenic Activities for Promoting Infected Wound Healing.","authors":"Yin, Weiling; Xia, Xiaowei; Liu, Yang; Zhang, Yijian; Wang, Miao; Zhu, Xuesong; Guo, Li; Pan, Guoqing","year":2026,"journal":"Biomedical materials (Bristol, England)","doi":"10.1088/1748-605X/ae4d95","pmid":"41780171","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16502","title":"Association of baseline characteristics with clinical outcomes of tirzepatide treatment in Japanese patients with obesity disease: A subgroup analysis of the SURMOUNT-J trial.","authors":"Yokote, Koutaro; Fukushima, Yasushi; Shingaki, Tomotaka; Oura, Tomonori; Ogawa, Wataru","year":2026,"journal":"Diabetes, obesity & metabolism, 28(2), 1278-1287","doi":"10.1111/dom.70315","pmid":"41290555","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16503","title":"GLP-1 receptor agonist suppresses fatty infiltration while improving range of motion and electromyographic function in a chronic rotator cuff tear rat model.","authors":"Yoon, Jong Pil; Park, Sung-Jin; Kim, Dong-Hyun; Lee, Hyun Joo; Kim, Jun-Young; Pham, Dinh The; Cho, Chul-Hyun; Chung, Seok Won","year":2026,"journal":"Journal of shoulder and elbow surgery","doi":"10.1016/j.jse.2025.12.019","pmid":"41644032","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Liraglutide produced striking improvements across all measured outcomes in the chronic rotator cuff tear model:\n\n- **Fatty infiltration**: 1.11 ± 0.75% vs 11.82 ± 3.89% (P<0.001) — a roughly 90% reduction\n- **Internal rotation**: 79 ± 38° vs 70 ± 2° (P<0.001)\n- **External rotation**: 55 ± 2° vs 48 ± 3° (P<0.001)\n- **Nerve-muscle signal strength**: 19.43 ± 8.77 mV vs 7.61 ± 3.15 mV (P=0.028) — more than doubled\n\nHistological analysis confirmed markedly decreased adipocyte deposition and preserved muscle fiber morphology in the liraglutide group. These results suggest GLP-1 receptor agonists can attenuate the otherwise irreversible muscle degeneration following rotator cuff tears.","whyItMatters":"Fatty infiltration after rotator cuff tears is one of the most vexing problems in orthopedic surgery. Once muscle turns to fat, it doesn't come back — even after surgical repair. No drug has been validated to prevent or reverse this degeneration. If GLP-1 agonists can be repurposed for this indication, it would represent a paradigm shift for millions of rotator cuff patients. The fact that liraglutide is already FDA-approved for other conditions could accelerate clinical translation.","specificNumbers":"","methodology":"Adult male rats underwent unilateral supraspinatus tendon transection with a silicone tube placed to prevent healing. After 2 weeks to allow the chronic tear to establish, rats were randomly assigned to receive daily intraperitoneal liraglutide (250 μg/kg/day) or saline for 4 weeks. At 6 weeks post-surgery, outcomes were assessed via Oil Red O staining (fatty infiltration), H&E histology (muscle morphology), goniometer (passive range of motion), and compound muscle action potential recordings (neuromuscular function).","limitations":"This is a preclinical rat model, and the rotator cuff anatomy differs from humans. The silicone tube interposition creates a specific injury model that may not perfectly replicate all types of human rotator cuff tears. Treatment started 2 weeks post-injury — it's unclear whether starting later (as often happens clinically) would be effective. Liraglutide was given systemically, so effects on body weight and metabolism could confound the musculoskeletal outcomes. Sample size was not reported in the abstract."},{"rthcId":"RPEP-16504","title":"Sex-specific differences in left atrial reverse remodelling after successful catheter ablation for atrial fibrillation.","authors":"Yoshida, Yuriko; Nakanishi, Koki; Daimon, Masao; Hirose, Kazutoshi; Iwama, Kentaro; Mukai, Yasuhiro; Yamamoto, Yuko; Seki, Hikari; Hirokawa, Megumi; Nakao, Tomoko; Oshima, Tsukasa; Matsubara, Takumi; Shimizu, Yu; Oguri, Gaku; Kojima, Toshiya; Hasumi, Eriko; Fujiu, Katsuhito; Morita, Hiroyuki; Kurano, Makoto; Takeda, Norihiko","year":2026,"journal":"European heart journal. Cardiovascular Imaging, 27(3), 480-487","doi":"10.1093/ehjci/jeaf309","pmid":"41206217","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16505","title":"Effect of Caerin 1.9 Antimicrobial Peptide Gel on Early Bacterial Infections in Oral Titanium Implants: An Animal Study.","authors":"You, Hang; Sun, Jiangling; Qin, Li; Fu, Quanlan; Rong, Meiyan; Wang, Tianfang; Li, Hejie; Liu, Xiaosong; Ni, Guoying; Yang, Wei","year":2026,"journal":"International dental journal, 76(1), 103991","doi":"10.1016/j.identj.2025.103991","pmid":"41270443","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16506","title":"Target trial emulations for tirzepatide, semaglutide and SGLT2-inhibitors for dementia in patients with type 2 diabetes: Real world evidence from a retrospective cohort study.","authors":"Younis, Alhena; Henney, Alex E; Riley, David R; Anson, Matthew; Zhao, Sizheng S; Ibarburu, Gema H; Malik, Rayaz A; Su, Li; Lip, Gregory Y H; Cuthbertson, Daniel J; Alam, Uazman","year":2026,"journal":"Diabetes research and clinical practice, 113083","doi":"10.1016/j.diabres.2026.113083","pmid":"41544899","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Three target trial emulations using propensity score-matched real-world data compared dementia outcomes across diabetes medications over two years:\n\n- Tirzepatide vs. SGLT2 inhibitors (n=14,462): HR 0.66 (95% CI 0.47–0.93, p=0.02) for dementia\n- Semaglutide vs. SGLT2 inhibitors (n=57,959): results not specified for dementia HR\n- Tirzepatide vs. semaglutide (n=12,246): HR 0.69 (95% CI 0.48–0.99, p=0.04) for dementia\n\nTirzepatide also showed lower all-cause mortality vs. both semaglutide (HR 0.72, 95% CI 0.58–0.90) and SGLT2 inhibitors (HR 0.29, 95% CI 0.23–0.37). Both tirzepatide and semaglutide reduced major adverse cardiovascular events (MACE) compared to SGLT2 inhibitors.","whyItMatters":"Dementia is a growing global health crisis with few effective treatments. If certain diabetes medications can reduce dementia risk as a side benefit, this could influence prescribing decisions for the millions of people with type 2 diabetes who are already at elevated dementia risk.","specificNumbers":"","methodology":"Researchers conducted three target trial emulations using the TriNetX global federated research network, a large real-world database. Adults with type 2 diabetes and no baseline dementia were included. Propensity score matching was used to balance groups, and survival analysis tracked first dementia diagnosis, MACE, and all-cause mortality over two years.","limitations":"This is an observational study using real-world data, not a randomized controlled trial, so it cannot prove causation. Unmeasured confounders may exist despite propensity score matching. The two-year follow-up is relatively short for dementia outcomes. Tirzepatide has been available for less time than the comparators, so follow-up duration may differ. The authors explicitly note these findings are hypothesis-generating."},{"rthcId":"RPEP-16507","title":"Dap-modified antimicrobial peptides exhibit enhanced antimicrobial activity and potential for bacterial infection therapy.","authors":"Yu, Chunlin; Guo, Feilu; Nie, Xin; Shang, Dejing; Dong, Weibing","year":2026,"journal":"Bioorganic chemistry, 174, 109703","doi":"10.1016/j.bioorg.2026.109703","pmid":"41780271","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Six Dap/Dab-modified analogues of the arginine-rich peptide W3R6 were synthesized and tested:\n\n• Lead compound W3R6-A1: MIC against MRSA improved from 6.25 μM to 0.78 μM (8-fold enhancement)\n• All analogues showed reduced cytotoxicity: >80% mammalian cell viability at 100 μM\n• W3R6-A2 and -A3 showed improved serum stability (higher residual amounts after 3 hours)\n• Dap-modified analogues disrupted bacterial cell membranes and biofilms\n• Lower tendency to induce drug resistance compared to conventional antibiotics\n• In vivo efficacy in two mouse infection models:\n  - Burn infection: reduced bacterial load and tissue damage\n  - Peritonitis-sepsis: decreased bacterial burden and pro-inflammatory cytokines (TNF-α, IL-6, IL-1β)\n• No in vivo toxicity observed","whyItMatters":"MRSA kills tens of thousands of people annually and is resistant to most antibiotics. The 8-fold improvement in antimicrobial potency achieved simply by incorporating a non-natural amino acid demonstrates a practical strategy for upgrading existing antimicrobial peptides. The dual benefit — more killing power with less toxicity — addresses the two main barriers to clinical development of AMPs. The successful in vivo results in relevant infection models move this beyond academic curiosity toward genuine therapeutic potential.","specificNumbers":"","methodology":"Six analogues were synthesized by replacing arginine or tryptophan residues with non-natural amino acids Dap (2,3-diaminopropionic acid) or Dab (2,3-diaminobutanoic acid). Testing included: MIC determination against multiple bacteria including MRSA, hemolytic activity, cytotoxicity assays, serum stability, mechanism of action studies (membrane disruption, biofilm disruption), resistance induction assays, and two mouse infection models (burn wound infection and peritonitis-sepsis) with histopathology and cytokine measurements.","limitations":"Preclinical study in cell cultures and mice — no human data. Mouse infection models may not perfectly predict human outcomes. Only one lead compound (W3R6-A1) was tested in vivo, though six analogues were synthesized. Long-term toxicity and pharmacokinetic profiles were not characterized. Manufacturing scalability and cost of non-natural amino acid incorporation were not addressed. Resistance development was assessed short-term; long-term resistance potential is unknown."},{"rthcId":"RPEP-16508","title":"Functional Peptide-Based Biomaterials for Pharmaceutical Application: Sequences, Mechanisms, and Optimization Strategies.","authors":"Yu, Dedong; Han, Nari; Son, Hyejeong; Kim, Sun Jo; Kweon, Seho","year":2026,"journal":"Journal of functional biomaterials, 17(1)","doi":"10.3390/jfb17010037","pmid":"41590805","tags":["drug-delivery","self-assembly","cell-penetrating-peptides","peptide-design"],"studyType":"review","evidenceStrength":"n/a-review","keyFinding":"The review organizes peptide-based biomaterials into three major functional categories:\n\n1. **Peptide excipients**: Cell-penetrating peptides (CPPs) enable intracellular delivery via direct membrane penetration or endocytosis; tight junction modulating peptides open passages between cells; peptide surfactants and stabilizers protect drug formulations.\n\n2. **Self-assembling peptides**: These spontaneously form nanospheres, cyclic nanotubes, nanovesicles, micelles, hydrogels, and depot systems for controlled and sustained drug release.\n\n3. **Peptide linkers**: Used in antibody-drug conjugates (ADCs), peptide-drug conjugates (PDCs), and prodrugs to achieve site-specific drug release triggered by tumor-associated enzymes or pH changes.\n\nOptimization strategies include cyclization, stapling, D-amino acid incorporation, functional motif integration, and AI-assisted combinatorial discovery.","whyItMatters":"Drug delivery is often the biggest bottleneck in turning a promising therapeutic molecule into an effective medicine. Peptide-based biomaterials solve multiple delivery challenges — getting drugs inside cells, controlling release timing, targeting specific tissues, and improving stability. This review provides a unified framework for understanding the full spectrum of peptide delivery technologies, which is increasingly important as the field moves toward more complex therapeutic modalities like gene therapies, siRNA drugs, and targeted cancer conjugates that all depend on effective delivery.","specificNumbers":"Covers CPPs, tight junction peptides, surfactants, nanospheres, nanotubes, nanovesicles, micelles, hydrogels, depots, ADC/PDC/prodrug linkers; optimization via cyclization, stapling, D-amino acids, AI","methodology":"Systematic literature review collating advances across peptide excipients, self-assembling peptide systems, and peptide linkers for drug delivery. Covers sequence-based optimization strategies with examples from both marketed drugs and research-stage candidates.","limitations":"As a broad review, it necessarily covers each topic at a survey level rather than providing deep mechanistic detail on any single technology. The review doesn't include original data. Specifics about clinical outcomes, safety profiles, or comparative efficacy of different delivery approaches are limited. The rapidly evolving nature of the field means some of the research-stage candidates discussed may have progressed or been abandoned since the review was compiled."},{"rthcId":"RPEP-16509","title":"Precise atorvastatin delivery by cardiac homing peptide functionalized nanoliposomes for myocardial damage repair after myocardial infarction.","authors":"Yu, Hongqin; Li, Shuai; Niu, Hongtao; Li, Zhao; Gai, Yusheng; Sun, Bei; Zhao, Lan","year":2026,"journal":"Nanomedicine (London, England), 21(6), 789-801","doi":"10.1080/17435889.2026.2628309","pmid":"41660754","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16510","title":"Flavor strengthening Maillard-modified peptides of hydrolyzed corn protein: auxiliary bacteriostatic function on spare rib broth and its underlying mechanism.","authors":"Yu, Jingyang; Zhou, Ye; Yao, Yishun; Zhang, Foxin; Xia, Shuqin; Cui, Heping; Hayat, Khizar; Zhang, Xiaoming","year":2026,"journal":"Journal of the science of food and agriculture, 106(4), 2007-2019","doi":"10.1002/jsfa.70220","pmid":"41392505","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16511","title":"Uncovering evolutionarily remote and highly potent antimicrobial peptides with protein language models.","authors":"Yu, Qinze; Liu, Hongbin; Shi, Haimei; Abdrakhmanov, Yerzhan; Shen, Junbo; Zhang, Chunhe; Dong, Zhihang; Zong, Licheng; Si, Longlong; Dai, Lei; Li, Yu","year":2026,"journal":"Nature biomedical engineering","doi":"10.1038/s41551-026-01630-w","pmid":"41776033","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16512","title":"Tryptophan-Containing Antimicrobial Peptides Attenuate Colorectal Cancer Progression by Inhibiting the Growth of Fusobacterium nucleatum.","authors":"Yu, Rui; Yu, Chunlin; Bi, Hongbo; Shang, Dejing; Dong, Weibing","year":2026,"journal":"ACS infectious diseases, 12(1), 265-275","doi":"10.1021/acsinfecdis.5c00800","pmid":"41328741","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16513","title":"Self-decreasing pH hydrolysis produces absorbed soybean peptides with enhanced hepatoprotection: The indispensable role of a tunable aromatic-pro-Arg/Lys motif.","authors":"Yu, Shengjuan; Zhang, Qiaoli; Liu, Wanlu; Han, Yu; Jenis, Janar; Liu, Xinqi; Li, He","year":2026,"journal":"Food research international (Ottawa, Ont.), 225, 118118","doi":"10.1016/j.foodres.2025.118118","pmid":"41508518","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Self-decreasing pH hydrolysis produced soybean peptides with the most potent hepatoprotective activity among three hydrolysis strategies tested. After simulated digestion and absorption through a Caco-2/HepG2 co-culture model, these peptides significantly reduced liver damage markers — AST levels dropped to 5.01 U/L and ALT to 0.91 U/L in ethanol-injured liver cells.\n\nTwo key peptides were identified: PFPRPQP, which activates the Nrf2 antioxidant pathway by binding to Keap1, and PIPFPR, which targets CYP2E1 (the enzyme that generates toxic acetaldehyde during alcohol metabolism) for potential enzyme inhibition. Both peptides contain an aromatic-Pro-Arg/Lys (Φ-P-R/K) core motif that molecular docking and amino acid substitution experiments showed is essential for their hepatoprotective activity. The sequential hydrolysis group had the highest apparent permeability coefficient (44.47 × 10⁻⁷ cm/s) but not the strongest protective effect, demonstrating that absorption efficiency alone doesn't determine efficacy.","whyItMatters":"Alcoholic liver disease is a global health burden with limited treatment options. Identifying specific food-derived peptide sequences that protect liver cells — along with their exact mechanisms of action — opens the door to developing targeted nutraceuticals. The discovery that a tunable structural motif controls activity means researchers can potentially engineer even more potent protective peptides based on this template.","specificNumbers":"","methodology":"Researchers compared three enzymatic hydrolysis strategies using alcalase, papain, and flavourzyme: self-decreasing pH hydrolysis, simultaneous multi-enzyme hydrolysis, and sequential multi-step hydrolysis. Resulting peptides underwent simulated gastrointestinal digestion and intestinal absorption using a Caco-2/HepG2 cell co-culture model. Key peptides were identified by mass spectrometry and validated through molecular docking simulations and amino acid substitution experiments to determine structure-activity relationships.","limitations":"All experiments were conducted in cell culture models (Caco-2 and HepG2 cells), not in living organisms or humans. The simulated digestion model may not fully replicate the complexity of human gastrointestinal processing. The hepatoprotective effects were measured only against acute ethanol exposure, not chronic alcohol consumption. Specific dosing for potential human use was not established."},{"rthcId":"RPEP-16514","title":"Structural diversity and evolutionary dynamics of the neuropeptide Y receptor Y8b across various teleosts.","authors":"Yu, Xiao-Zheng; Chen, Hang-Tao; Liu, Zi-Yan","year":2026,"journal":"Comparative biochemistry and physiology. Part D, Genomics & proteomics, 59, 101803","doi":"10.1016/j.cbd.2026.101803","pmid":"41785562","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16515","title":"A study to evaluate the impact of PB-119 injection (a pegylated exenatide formulation) on the pharmacokinetic profiles of Digoxin and Warfarin sodium in healthy subjects.","authors":"Yu, Yang; Hu, Wang; Zhang, Tonghao; Peng, Yu; Ding, Jiaxiang; Wang, Xiaoni; He, Hongwei; Zhou, Daolei; Han, Dongshuang; Cao, Jie; Cheng, Ning; Zhou, Jinmei; Zhou, Huan","year":2026,"journal":"SAGE open medicine, 14, 20503121261424728","doi":"10.1177/20503121261424728","pmid":"41732153","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16516","title":"Association of glucagon-like peptide-1 receptor agonist use with clinical outcomes in patients with rheumatoid arthritis and type 2 diabetes.","authors":"Yu, Yu-Ting; Lee, Ying Chun; Fang, Yu-Wei; Hsieh, Wen-Hui; Tsai, Ming-Hsien","year":2026,"journal":"Journal of diabetes investigation","doi":"10.1111/jdi.70281","pmid":"41793207","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16517","title":"Differences in serum neuropeptide Y levels and appetite changes in patients with major depressive disorder stratified by sex and reproductive aging.","authors":"Yuan, Qianfa; Wang, Li; Zhuang, Yuan; Lin, Duoduo; Xu, Zhizhong; Wen, Chunyan; Su, Weichao; Huang, Zhiyuan; Qiu, Yan","year":2026,"journal":"BMC psychiatry, 26(1), 111","doi":"10.1186/s12888-025-07753-9","pmid":"41484969","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Among 210 MDD patients divided into three groups:\n\n- Premenopausal women (n=80): NPY = 280.80 ± 35.50 pg/mL (highest)\n- Men (n=65): NPY = 250.50 pg/mL (estimated from differences)\n- Postmenopausal women (n=65): NPY = 252.10 pg/mL (estimated from differences)\n\nKey findings:\n- Premenopausal women's NPY was significantly higher than men (Δ=30.30, p=0.007) and postmenopausal women (Δ=28.70, p=0.009)\n- No difference between postmenopausal women and men (Δ=1.60, p=0.989)\n- Similar group patterns were seen for appetite (VAS scores)\n- NPY positively correlated with appetite (r=0.422-0.437)\n- The NPY-appetite correlation was strongest in premenopausal women and weakest in postmenopausal women (β=0.007, p=0.021)\n- Correlation held after controlling for depression severity","whyItMatters":"Depression affects appetite differently in men and women, but the biological reasons have been poorly understood. This study shows that neuropeptide Y — a key appetite-regulating peptide — varies dramatically by sex and menopausal status in depressed patients. This suggests that the appetite disturbances in depression may require different management strategies for premenopausal women versus men or postmenopausal women, potentially informing the choice of antidepressants and nutritional support.","specificNumbers":"","methodology":"Cross-sectional study of 210 patients with major depressive disorder. Participants were divided by sex and reproductive status: males (n=65), premenopausal women (n=80), postmenopausal women (n=65). Serum NPY levels were measured by ELISA. Appetite was assessed using a visual analog scale (VAS). Depression severity was evaluated with the 17-item Hamilton Depression Rating Scale (HDRS-17). Statistical analysis included one-way ANOVA with post-hoc tests and stratified regression models.","limitations":"The study lacked a healthy control group, so it cannot determine whether the observed NPY differences are specific to depression or reflect general population differences between sexes and menopausal status. Cross-sectional design prevents causal conclusions. Serum NPY may not directly reflect brain NPY levels. Hormonal status (estrogen, progesterone) was not directly measured. The study did not control for antidepressant medication use, which could affect NPY levels. The abstract contains apparent formatting errors in the statistical reporting."},{"rthcId":"RPEP-16518","title":"Molecular Diversity, Structure-Function Relationship, Mechanism of Action, and Transformative Potential of Black Soldier Fly Antimicrobial Peptides Against Multidrug-Resistant Pathogens.","authors":"Yuan, Ru-Xi; Ma, Xiao-Yang; Lv, Yang; Si, Hong-Bin","year":2026,"journal":"Current issues in molecular biology, 48(1)","doi":"10.3390/cimb48010062","pmid":"41614891","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16519","title":"Risk of prostatitis in patients with type 2 diabetes mellitus: An observational retrospective cohort study of canagliflozin versus other antihyperglycemic agents using propensity score matching.","authors":"Yuan, Zhong; Jeffcoat, Carolyn H; Ali, Saberi Rana; Sena, Anthony G; Schuemie, Martijn J; Ryan, Patrick B; Fonseca, Sergio A","year":2026,"journal":"PloS one, 21(2), e0341745","doi":"10.1371/journal.pone.0341745","pmid":"41628085","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16520","title":"Engineering of antimicrobial peptides by surface display technologies.","authors":"Yuceer, Sugra; Yalcin, Husniye Tansel; Kalyoncu, Sibel","year":2026,"journal":"Advances in protein chemistry and structural biology, 149, 115-141","doi":"10.1016/bs.apcsb.2025.04.004","pmid":"41581930","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16521","title":"Synergistic mechanism of plasma and melittin-induced membrane perforation in sialic acid-targeted cancer cells.","authors":"Yue, Yi; Zhao, Tong; Cui, Yanxiu; Wang, Xiaolong; Sun, Ying; Zhang, Yuantao","year":2026,"journal":"The Journal of chemical physics, 164(6)","doi":"10.1063/5.0317210","pmid":"41661048","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16522","title":"Preliminary Real-World Experience with Semaglutide in Obese Patients with Type 2 Diabetes on Chronic Hemodialysis: A Multicenter Pilot Study.","authors":"Yugueros, Alejandra; D'Marco, Luis; Valero, Alejandro; Vivó, Elena; Martínez-Mas, Amparo; Calvé, Manuel; Alonso, Juan Carlos; Vizcaíno, Belén; González-Moya, Mercedes; Checa-Ros, Ana; Sancho, Asunción; Molina, Pablo","year":2026,"journal":"Medicina (Kaunas, Lithuania), 62(2)","doi":"10.3390/medicina62020386","pmid":"41752784","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16523","title":"Perioperative Glucagon-Like Peptide-1 Receptor Agonist Therapy and Postoperative Outcomes in Adult Foot and Ankle Surgery: A Scoping Review.","authors":"Zahed, Mohamed; Alesawy, Alzahraa Faris; Elkohail, Ahmed; Ghazi, Ahmed; Fell, Adam; Hashem, Mohamed","year":2026,"journal":"Cureus, 18(1), e101653","doi":"10.7759/cureus.101653","pmid":"41700259","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16524","title":"Combination therapy with VEGFR2 nanoliposomal peptide and paclitaxel in murine models of melanoma: a promising strategy for enhancing the efficacy of cancer immunotherapy.","authors":"Zahedipour, Fatemeh; Vahdat-Lasemi, Fatemeh; Farhoudi, Leila; Hosseinikhah, Seyedeh Maryam; Amiri, Atefeh; Barati, Mehdi; Sankian, Mojtaba; Zamani, Parvin; Gheybi, Fatemeh; Jamialahmadi, Khadijeh; Jaafari, Mahmoud Reza","year":2026,"journal":"International immunopharmacology, 169, 116008","doi":"10.1016/j.intimp.2025.116008","pmid":"41365201","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16525","title":"PeptideNet: An Integrative Deep Learning Framework for Predicting Diverse Bioactive Peptides Using Protein Language Model Embeddings.","authors":"Zahid, Hamza; Maryam; To Chong, Kil; Tayara, Hilal","year":2026,"journal":"Journal of chemical information and modeling","doi":"10.1021/acs.jcim.5c02885","pmid":"41731742","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"PeptideNet achieved strong predictive accuracy on independent test datasets across five bioactive peptide categories:\n\n• Antiviral peptides: 93% accuracy\n• Antimicrobial peptides: 94% accuracy\n• Antioxidative peptides: 84% accuracy\n• Anti-cell-penetrating peptides: 89% accuracy\n• Antihemolytic peptides: 87% accuracy\n\nESM-2 protein language model embeddings consistently outperformed other feature representations (ESM-1, ProtBert, physicochemical descriptors) across all peptide types. The hybrid CNN-BiGRU architecture captured both local sequence motifs and long-range dependencies in peptide sequences. Visualization analysis confirmed the model learned meaningful representations and identified conserved amino acid patterns linked to bioactivity.","whyItMatters":"Discovering new bioactive peptides through lab experiments is slow and expensive. PeptideNet offers a computational shortcut — screen millions of peptide sequences in silico to identify the most promising candidates before committing to wet-lab testing. The 84-94% accuracy means the system is reliable enough to meaningfully reduce the number of candidates that need experimental validation, potentially accelerating peptide drug discovery by orders of magnitude.","specificNumbers":"","methodology":"The researchers developed 20 hybrid deep learning models combining Convolutional Neural Networks (CNNs) with Bidirectional Gated Recurrent Units (BiGRUs). Four feature representations were tested: three protein language model embeddings (ESM-1, ESM-2, ProtBert) and physicochemical descriptors. Models were trained on five categories of bioactive peptides and evaluated on independent test datasets. t-SNE visualization assessed model generalization, and positional sequence logo analysis identified conserved residue patterns.","limitations":"The model was evaluated on curated benchmark datasets, which may not fully represent the diversity of peptides encountered in real-world drug discovery. Prediction accuracy varied across categories (84-94%), with antioxidative peptides being harder to predict. The study focused on binary classification (active/inactive) rather than predicting potency or selectivity. Computational predictions always require experimental validation, and false positives could waste lab resources. The model also doesn't account for peptide stability, toxicity, or manufacturability."},{"rthcId":"RPEP-16526","title":"Engineered Stable, Antibiotic-Free, High-Level Protein Expression in the Probiotic Chassis Escherichia coli Nissle 1917.","authors":"Zainuddin, Halimatun Sakdiah; Murali, Sanjeeva Kumar; Mansell, Thomas J","year":2026,"journal":"Biotechnology and bioengineering, 123(3), 776-784","doi":"10.1002/bit.70130","pmid":"41437924","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16527","title":"Peptide receptor radionuclide therapy (PRRT) in high grade neuroendocrine neoplasms: a systematic review and meta-analysis.","authors":"Zampella, Emilia; Piscopo, Leandra; Green, Roberta; Cantoni, Valeria; Nappi, Carmela; Gaudieri, Valeria; Caiazzo, Elisa; Scaglione, Mariano; Cuocolo, Alberto; Klain, Michele","year":2026,"journal":"European journal of nuclear medicine and molecular imaging","doi":"10.1007/s00259-025-07726-w","pmid":"41483309","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across 7 studies totaling 317 patients with grade 3 (G3) gastro-entero-pancreatic neuroendocrine neoplasms:\n\n- Objective response rate (ORR): 34% (95% CI: 22–46%) — meaning about one-third of patients had measurable tumor shrinkage\n- Disease control rate (DCR): 64% (95% CI: 52–76%) — meaning nearly two-thirds had their disease stabilize or shrink\n- Median progression-free survival: 13.88 months (95% CI: 10.33–18.64)\n- Median overall survival: 29.95 months (95% CI: 19.80–45.30)\n\nThe treatments used were [¹⁷⁷Lu]Lu-DOTA-TATE and/or [⁹⁰Y]Y-SSA, which are radioactive versions of somatostatin analog peptides that target receptors on tumor cells.","whyItMatters":"High-grade (G3) neuroendocrine neoplasms have historically been considered too aggressive for PRRT, which was initially approved mainly for well-differentiated, lower-grade tumors. This meta-analysis provides the strongest pooled evidence to date that PRRT can still benefit these sicker patients — a 64% disease control rate and median survival of nearly 2.5 years are clinically meaningful results for a cancer with few effective options.","specificNumbers":"","methodology":"The researchers conducted a systematic review and meta-analysis searching PubMed and Embase for all clinical studies published through March 2025. They included studies of patients with grade 3 GEP-NEN treated with radiolabeled somatostatin analogs. Response was evaluated using RECIST 1.1 criteria (the standard method for measuring tumor response). Funnel plot analysis indicated no publication bias. Some studies also stratified patients by Ki-67 values, a marker of tumor aggressiveness.","limitations":"Only 7 studies met inclusion criteria, with a total of 317 patients — relatively small for a meta-analysis. All studies were retrospective or observational (no randomized controlled trials). There was variability in treatment protocols, patient selection, and how outcomes were measured. Only 3 studies fully reported overall survival data. The heterogeneity in Ki-67 cutoffs and tumor differentiation within the G3 category could mask important differences in response."},{"rthcId":"RPEP-16528","title":"PGLa and Magainin 2 Can Porate Membranes via Transient Hourglass-Shaped Toroidal Pores.","authors":"Zan, Bing; Chen, Charles H; Mateen, Akilah I; Kolenovic, Belmin; Wiedman, Gregory R; Ulmschneider, Martin B; Ulmschneider, Jakob P","year":2026,"journal":"Journal of the American Chemical Society, 148(2), 2191-2205","doi":"10.1021/jacs.5c11101","pmid":"41486758","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16529","title":"Genetically Simulated GLP-1 Receptor Agonism and Cerebral Small Vessel Disease.","authors":"Zangas, Panagiotis; Omarov, Murad; Georgakis, Marios K","year":2026,"journal":"Neurology. Genetics, 12(2), e200359","doi":"10.1212/NXG.0000000000200359","pmid":"41773243","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16530","title":"Structure-Guided Design of Temporin-Derived Peptides Reveals Potent Dual-Mechanism Inhibitors of SARS-CoV-2.","authors":"Zannella, Carla; Fernandez, Feliciana Real; Santoro, Federica; Bellavita, Rosa; Casciaro, Bruno; Rovero, Paolo; Nencioni, Lucia; De Angelis, Marta; De Filippis, Anna; Galdiero, Massimiliano; Brancaccio, Diego; Merlino, Francesco; Grieco, Paolo; Mangoni, Maria Luisa; Carotenuto, Alfonso","year":2026,"journal":"Journal of medicinal chemistry, 69(3), 3331-3342","doi":"10.1021/acs.jmedchem.5c03196","pmid":"41622708","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16531","title":"Enzyme responsive antimicrobial hyaluronan-nanocellulose hybrid wound dressings for the treatment of infected wounds.","authors":"Zattarin, Elisa; Bekele Kebede, Wasihun; Sotra, Zeljana; Shamasha, Rozalin; Starkenberg, Annika; Guerrero-Florez, Valentina; Pramod Khare, Lalit; Bengtsson, Torbjörn; Khalaf, Hazem; Björk, Emma M; Rakar, Jonathan; Junker, Johan P E; Aili, Daniel","year":2026,"journal":"Bioactive materials, 61, 150-171","doi":"10.1016/j.bioactmat.2026.01.042","pmid":"41716672","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16532","title":"Antigenic-Specificity and Cytokine Profile of the T-Cell Response to Human Cytomegalovirus in Transplant Recipients.","authors":"Zavaglio, Federica; Zelini, Paola; Cera, Asja; d'Angelo, Piera; Gregorini, Marilena; Rampino, Teresa; Del Frate, Lucia; Meloni, Federica; Borsani, Oscar; Pellegrini, Carlo; Baldanti, Fausto; Lilleri, Daniele","year":2026,"journal":"Pathogens (Basel, Switzerland), 15(1)","doi":"10.3390/pathogens15010053","pmid":"41599037","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16533","title":"Liraglutide enhances bone regeneration in a critical-size calvarial defect model in male rats: A comparative study with autogenous grafts, allografts, and xenografts.","authors":"Zavrak, Necati; Lektemur Alpan, Aysan; Özmen, Özlem","year":2026,"journal":"Archives of oral biology, 184, 106519","doi":"10.1016/j.archoralbio.2026.106519","pmid":"41579495","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16534","title":"Paving the Way for CCK2R-Targeted Peptide Receptor Radionuclide Therapy with [177Lu]Lu-DOTA-MGS5 in Patients with Small Cell Lung Cancer.","authors":"Zavvar, Taraneh Sadat; Santo, Giulia; Gruber, Leonhard; Kronthaler, Ariane; Hagenbuchner, Judith; Skvortsova, Ira; Piro, Inken; Steiger, Katja; Martinovic, Vladan; Minasch, Danijela; Löffler-Ragg, Judith; di Santo, Gianpaolo; Virgolini, Irene J; von Guggenberg, Elisabeth","year":2026,"journal":"Pharmaceutics, 18(1)","doi":"10.3390/pharmaceutics18010138","pmid":"41599245","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16535","title":"The effect of GLP-1 receptor agonist and SGLT2 inhibitor on infection risk: network meta-analysis.","authors":"Zeng, Bing-Syuan; Chen, Jiann-Jy; Hsu, Chih-Wei; Hung, Chao-Ming; Zeng, Bing-Yan; Suen, Mein-Woei; Yang, Wei-Chieh; Wang, Hung-Yu; Shiue, Yow-Ling; Su, Kuan-Pin; Li, Cheng-Ta; Liang, Chih-Sung; Stubbs, Brendon; Chen, Yen-Wen; Lei, Wei-Te; Chen, Tien-Yu; Hsu, Shih-Pin; Tseng, Ping-Tao","year":2026,"journal":"Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases","doi":"10.1016/j.cmi.2026.01.014","pmid":"41610949","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16536","title":"Peptidomics-derived peptides enhance antiviral defense against ChiVMV in Nicotiana tabacum.","authors":"Zeng, Jianmin; Huang, Changjun; Liu, Yong; Yu, Haiqin; Tong, Zhijun; Xiao, Bingguang; Yuan, Cheng","year":2026,"journal":"Biochemical and biophysical research communications, 799, 153262","doi":"10.1016/j.bbrc.2026.153262","pmid":"41519052","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16537","title":"Gut-lung axis: a novel mechanism involving microbiota dysbiosis-coordinated PLA2-TRPV1 neuroimmune crosstalk in nanoplastic-induced asthma exacerbation.","authors":"Zeng, Xin; He, Chuhao; Li, Jitong; Feng, Qing; Lu, Zhenjie; Li, Long; Qiao, Yongkang; Han, Wei; Wang, Faming; Chen, Mingqing; Lu, Chan; She, Rong; Wu, Yang; Sun, Yanling; Yang, Xu; Ma, Ping; Lu, Surui","year":2026,"journal":"Environment international, 207, 110047","doi":"10.1016/j.envint.2026.110047","pmid":"41512508","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Nanoplastic exposure (20 nm polystyrene particles) worsened asthma in mice through a multi-step mechanism: the particles activated PLA2 in lung tissue, producing inflammatory metabolites that upregulated TRPV1 channels. This triggered release of neuropeptides substance P and calcitonin gene-related peptide (CGRP), which activated NF-κB signaling and amplified Th2 inflammation (elevated IL-4, IL-5, IL-13). Simultaneously, nanoplastics disrupted gut microbiota, increasing gram-negative bacteria that released LPS, activating the intestinal TLR4/NF-κB pathway and fueling lung inflammation through the gut-lung axis. Reduced short-chain fatty acid production from dysbiosis further enhanced lung PLA2 activity, creating a self-reinforcing PLA2-TRPV1-neuropeptide feedback loop.","whyItMatters":"This study reveals how environmental nanoplastic pollution could worsen respiratory diseases through neuropeptide-mediated neuroimmune crosstalk. The discovery that substance P and CGRP form part of a positive feedback loop connecting gut microbiota disruption to lung inflammation provides new therapeutic targets and highlights the broader health impacts of microplastic exposure.","specificNumbers":"20 nm polystyrene nanoparticles · elevated IL-4, IL-5, IL-13 · reduced IFN-γ · increased 8-OHdG · increased Pseudomonadota, Actinomycetota, Verrucomicrobiota · elevated prostaglandin E2 and leukotriene B4","methodology":"Researchers used an OVA-sensitized mouse model of asthma exposed to 20 nm polystyrene nanoplastics. They measured airway hyperresponsiveness, performed histopathological analysis of lung tissue (HE, PAS, Masson staining), detected PLA2 and TRPV1 expression by immunohistochemistry, quantified serum immunoglobulins and tissue cytokines, and conducted lung metabolomics and gut microbiota profiling.","limitations":"This is a mouse model study using a specific type and size of nanoplastic (20 nm polystyrene), which may not represent the diverse nanoplastics humans encounter. The OVA sensitization model is a standard but simplified representation of human asthma. Direct translation of the gut microbiota findings from mice to humans requires caution due to differences in microbiome composition."},{"rthcId":"RPEP-16538","title":"Correlation of Plasma Neuropeptide Y with Specific Cognitive Domains in Patients with Parkinson's Disease Cognitive Impairment.","authors":"Zhang, Ai-Rong; Wu, Min-Lu; Pang, Wen-Jun; Ning, Xian-Bin; Wu, Yu-Jun; Pang, Jin-Feng","year":2026,"journal":"Clinical laboratory, 72(1)","doi":"10.7754/Clin.Lab.2025.250237","pmid":"41543103","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16539","title":"Semaglutide exerts neuroprotective effects by blocking the interleukin-17/NOD-like receptor family pyrin domain containing 3-mediated neuroinflammation pathway after traumatic brain injury.","authors":"Zhang, Bin; Kong, Lu; Wang, Yumei; He, Wei; Yang, Mengshi; Zhang, Xueling; Chen, Xiyu; Zhang, Yaxuan; Liu, Baiyun; Bai, Miao; Shi, Guangzhi","year":2026,"journal":"Neural regeneration research","doi":"10.4103/NRR.NRR-D-25-00990","pmid":"41622481","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16540","title":"Quercetin Ameliorates Glucose Metabolism Dysregulation in CUMS Model Rats via the Bile Acid-FXR/TGR5 Axis.","authors":"Zhang, Bitao; Li, Yuanyuan; Fan, Peijian; Wang, Shaoxian","year":2026,"journal":"Biological & pharmaceutical bulletin, 49(1), 179-195","doi":"10.1248/bpb.b25-00528","pmid":"41605656","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16541","title":"AMPSeek: A Workflow for Predicting Antimicrobial Peptide Activity, Three-Dimensional Structure, and Toxicity.","authors":"Zhang, Emily; Ucar, Berke; Salehi, Ali; Warren, René L; Birol, Inanc","year":2026,"journal":"Current protocols, 6(2), e70325","doi":"10.1002/cpz1.70325","pmid":"41711565","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16542","title":"Oral administration of probiotic colony-like micro-nano system for immunoregulation of rheumatoid arthritis.","authors":"Zhang, Fangke; Ding, Tao; Zheng, Jiancheng; Li, Nan; Li, Zechuan; Wang, Xuefei; Du, Yawei; Hu, Weiguo; Cui, Wenguo; Guo, Weisheng","year":2026,"journal":"Acta pharmaceutica Sinica. B, 16(1), 444-457","doi":"10.1016/j.apsb.2025.10.038","pmid":"41584341","tags":["venom-derived-peptides","autoimmune-disease"],"studyType":"animal-and-cell","evidenceStrength":"preliminary","keyFinding":"Researchers created an oral delivery system for melittin — a bee venom peptide with anti-arthritic properties — by encapsulating it in a multi-layered micro-nano system. Sialic acid-decorated melittin nanoparticles were embedded in calcium alginate microgels, then coated with probiotic biofilms. This probiotic coating protected melittin from stomach acid destruction and helped it adhere to the intestinal wall.\n\nThe system accumulated in mesenteric lymph nodes (gut immune centers) and modulated key immune cell ratios — Th1/Th2 and Th17/Treg — in both lymph nodes and spleen tissue. This rebalancing of the immune system successfully alleviated arthritis progression in the animal model while reducing the off-target adverse effects that normally limit melittin's clinical use.","whyItMatters":"Rheumatoid arthritis requires lifelong treatment, and current drugs either suppress the immune system broadly (causing infections) or are expensive biologics that require injection. Melittin from bee venom has shown anti-arthritic immune-modulating effects, but it's destroyed by stomach acid and can be toxic when not targeted properly. This study solves both problems with an elegant triple-layer delivery system that protects the peptide, targets it to gut immune centers, and uses the gut-immune axis to treat a systemic autoimmune disease. If the concept works in humans, it could turn a venom peptide into an oral autoimmune therapy.","specificNumbers":"Melittin: bee venom peptide · sialic acid-decorated nanomedicines · calcium alginate microgels · probiotic biofilm coating · targets mesenteric lymph nodes · modulates Th1/Th2 and Th17/Treg ratios · alleviates arthritis progression","methodology":"Gas-shearing microfluidics was used to create monodisperse sialic acid-decorated melittin nanoparticles within calcium alginate microgels. The microspheres were coated with probiotic biofilms for acid resistance and intestinal adhesion. The system was administered orally to an animal model of rheumatoid arthritis. Immune cell ratios (Th1/Th2, Th17/Treg) were measured in mesenteric lymph nodes and spleen. Arthritis progression and adverse effects were assessed.","limitations":"This is a preclinical animal study with no human data. The multi-component delivery system is complex to manufacture, which could limit scalability and clinical translation. Long-term safety of repeated oral probiotic biofilm-coated nanoparticles is unknown. The specific animal arthritis model used is not described in the abstract. Melittin's known toxicity at higher doses remains a concern even with targeted delivery."},{"rthcId":"RPEP-16543","title":"CKAAKN peptide-conjugated long-circulating nanoliposomes for the targeted delivery of oridonin to pancreatic cancers.","authors":"Zhang, Fangxia; Luo, Kunshun; Xuan, Shaoyan; Chen, Teng; Chen, Zhiyong; Yang, Jing; Zhou, Ying; Feng, Tingting; Zhu, Yue; Wang, Zuhua","year":2026,"journal":"Scientific reports, 16(1), 6065","doi":"10.1038/s41598-026-36920-5","pmid":"41578142","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The CKAAKN peptide-conjugated nanoliposome (ORI@CPD-Lipo) demonstrated:\n\n- Average particle size of ~100 nm with good stability and biosafety\n- Selective internalization into BxPC-3 pancreatic cancer cells within 1–4 hours in vitro, compared to minimal uptake in normal HPDE6-C7 cells\n- Significantly higher tumor uptake in vivo over 1–48 hours compared to normal pancreatic tissue, with increasing ratios over time\n- Enhanced antitumor effect compared to free oridonin, non-targeting liposomes, and CKAAKN-blocked controls\n- The enhanced activity was attributed to peptide-mediated cellular uptake and sustained drug release from nanoparticles","whyItMatters":"Pancreatic cancer has one of the worst survival rates of any cancer, partly because drugs don't reach the tumor effectively. Using a targeting peptide to guide drug-loaded nanoparticles directly to cancer cells could significantly improve treatment efficacy while reducing side effects from off-target drug exposure. This peptide-targeted approach is applicable beyond oridonin to other anti-cancer agents.","specificNumbers":"","methodology":"Researchers developed PEGylated nanoliposomes modified with the CKAAKN tumor-targeting peptide to deliver oridonin. The formulation was characterized for size, stability, and safety. In vitro studies compared uptake in pancreatic cancer cells (BxPC-3) versus normal cells (HPDE6-C7). In vivo biodistribution was assessed in tumor-bearing mice. Antitumor efficacy was compared across free drug, non-targeting liposomes, targeted liposomes, and CKAAKN-blocked controls.","limitations":"This is a preclinical study using cell lines and mouse xenograft models, which may not fully reflect human pancreatic cancer complexity. The oridonin payload is a natural compound with limited clinical validation. Long-term safety, pharmacokinetics, and potential immunogenicity of the peptide-conjugated nanoliposomes in humans are unknown. Manufacturing scalability of the targeted nanoformulation was not addressed."},{"rthcId":"RPEP-16544","title":"A novel GIPR/GLP-1R dual agonist improves systemic metabolism through differentially regulating inflammation and lipid metabolism in obesity.","authors":"Zhang, Feng; Chen, Wei; Wang, Huiying; Wu, Dan; Chen, Zhinan; Cheng, Ruitang; Hu, Jinying; Xie, Lijun; Qiu, Yan; Zhou, Zhiguang; Li, Tian; Du, Zhiqiang; Hu, Fang","year":2026,"journal":"Journal of advanced research","doi":"10.1016/j.jare.2026.02.006","pmid":"41690462","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16545","title":"Within-host adaptation mutations associated with persistent colonization of Pseudomonas aeruginosa in a silicosis patient.","authors":"Zhang, Furong; Qian, Lvxin; Yan, Yi; Wan, Qiuling; Zhang, Luhua; Li, Ying","year":2026,"journal":"Frontiers in cellular and infection microbiology, 16, 1739179","doi":"10.3389/fcimb.2026.1739179","pmid":"41782941","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16546","title":"Multi-strategy embedded framework for neoantigen vaccine maturation.","authors":"Zhang, Guanqiao; Fu, Yaqi; Chan, Kevin C; Jin, Ruofan; Yang, Yuxuan; Fu, Lei; Zhou, Ruhong","year":2026,"journal":"Scientific reports, 16(1), 4503","doi":"10.1038/s41598-025-34618-8","pmid":"41554915","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16547","title":"VGLL4 modulates Paneth cells and sustains intestinal homeostasis.","authors":"Zhang, Haoen; Wang, Zuoyun; Wang, Xiaodong; Yu, Wentao; Zhang, Guoying; Zhang, Haijiao; Lu, Yi; Sun, Yang; Lu, Tiantian; Li, Xiaoyu; Yang, Ruizeng; Sun, Jiaqi; Xu, Jinjin; Huang, Shuo; Ma, Xueyan; Ren, Jiale; Tang, Nan; Cheng, Zhonghua; Yu, Jing; Wei, Fang; Zhou, Hu; Li, Jinsong; Qin, Jun; Jin, Yunyun; Zhang, Lei","year":2026,"journal":"EMBO reports","doi":"10.1038/s44319-026-00699-3","pmid":"41629625","tags":["antimicrobial-and-bioactive-peptides","gut-and-metabolic-peptides"],"studyType":"animal-study","evidenceStrength":"low-moderate","keyFinding":"The protein VGLL4 is essential for Paneth cell function and antimicrobial peptide production in the gut. When VGLL4 was deleted from intestinal epithelium, mice had fewer Paneth cells, produced less antimicrobial peptides (including defensins), developed gut microbiome imbalances (dysbiosis), and had impaired intestinal regeneration capacity.\n\nThe study identified two distinct mechanisms: VGLL4 teams up with TEAD4 and ATOH1 to drive Paneth cell differentiation via GFI1, and separately forms a complex with TEAD4 and TCF4 to directly induce defensin expression. Notably, VGLL4 expression drops during irradiation injury and DSS-induced colitis, and human colitis datasets also show reduced VGLL4 — suggesting this pathway may be compromised in inflammatory bowel disease.","whyItMatters":"Paneth cells are the gut's antimicrobial peptide factories — they produce defensins and other peptides that keep gut bacteria in check and maintain the stem cell niche. Discovering that VGLL4 controls both Paneth cell numbers and defensin production provides a new upstream target for understanding and potentially treating conditions where gut antimicrobial defense breaks down, including inflammatory bowel disease.","specificNumbers":"VGLL4 knockout in intestinal epithelium · Reduced Paneth cell numbers · Decreased AMP/defensin production · Microbiota dysbiosis · Impaired regeneration · VGLL4 reduced in human colitis datasets","methodology":"Conditional knockout mouse study deleting VGLL4 from intestinal epithelium. Researchers analyzed Paneth cell numbers, antimicrobial peptide expression, gut microbiome composition, and intestinal regeneration capacity. Molecular mechanisms were dissected through protein complex analysis (VGLL4-TEAD4-ATOH1 and VGLL4-TEAD4-TCF4). Human colitis gene expression datasets were used for clinical validation.","limitations":"Primarily a mouse study — direct translation to human gut defense requires caution. The human colitis data is correlational (reduced VGLL4 expression) without functional validation in human tissue. The specific antimicrobial peptides affected and the degree of microbiome disruption are not fully quantified in the abstract."},{"rthcId":"RPEP-16548","title":"Mechanically responsive yes-associated protein-inhibiting peptide hydrogel for scarless wound healing.","authors":"Zhang, Huiqi; Lu, Zhengmao; Liu, Wenshang; Luo, Dong; Hu, Manman; Pu, Xiaohui; Fan, Zhen; Shen, Zhengyu; Li, Meng","year":2026,"journal":"Acta biomaterialia, 209, 306-321","doi":"10.1016/j.actbio.2025.11.054","pmid":"41317824","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16549","title":"Intra-arterial peptide receptor radionuclide therapy (IA-PRRT) in patients with SSTR-expressing neuroendocrine neoplasms: short- and long-term safety and efficacy for up to 13 years.","authors":"Zhang, Jingjing; Mensel, Birger; Baum, Richard P","year":2026,"journal":"Theranostics, 16(4), 1658-1670","doi":"10.7150/thno.112012","pmid":"41356201","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16550","title":"RIPK3 inhibitor GSK872 targets angiotensin II induced cardiomyocyte hypertrophy by regulating Ca2+/ calmodulin dependent protein kinase II.","authors":"Zhang, Jingjing; Yu, Huijie; Yang, Yuxin; Liu, Ajie; Wang, Peng","year":2026,"journal":"PloS one, 21(1), e0334387","doi":"10.1371/journal.pone.0334387","pmid":"41499472","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16551","title":"GLP-1RAs and tirzepatide may reduce heart failure risk in obese but not in non-obese patients with cardiovascular or renal disease: A systematic review and meta-analysis.","authors":"Zhang, Ju; Guan, Xiangfeng; Kong, Mowei; Xia, Meng; Yu, Yang; Zhang, Chunxiang","year":2026,"journal":"Metabolism: clinical and experimental, 175, 156433","doi":"10.1016/j.metabol.2025.156433","pmid":"41207615","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16552","title":"Sintilimab-related fulminant autoimmune diabetes mellitus manifesting as diabetic ketoacidosis and rare insulin resistance: A case report and literature review.","authors":"Zhang, Junhui; Zhang, Yuping; Li, Hongmei; Deng, Fang; Ma, Liling; Yang, Wenjing; Yang, Hong; Yu, Huiqing; Chen, Bing; Hu, Jiongyu","year":2026,"journal":"Endocrine journal, 73(1), 93-99","doi":"10.1507/endocrj.EJ25-0295","pmid":"41083372","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16553","title":"Impact of rhBNP and ivabradine on outcomes, cardiac markers, and microcirculation in ischemic heart failure.","authors":"Zhang, Liqin; Jiang, Zhenhua; Ma, Hailiang; Dong, Liang; Feng, Shifen; Xu, Jin; Chen, Jie","year":2026,"journal":"Heart & lung : the journal of critical care, 75, 178-183","doi":"10.1016/j.hrtlng.2025.09.020","pmid":"41056634","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16554","title":"Lateral flow biosensors for low abundance detection of brain natriuretic peptide with enzyme-free amplification.","authors":"Zhang, Menghan; Xu, Tao; Jajesniak, Pawel; Core, Giulia; Zeng, Zhuoer; Shalaby, Maha Mansour Mohamed; Reboud, Julien; Cooper, Jonathan M","year":2026,"journal":"Lab on a chip, 26(3), 627-634","doi":"10.1039/d5lc00793c","pmid":"41504292","tags":["natriuretic-peptides","diagnostics"],"studyType":"methods-development","evidenceStrength":"preliminary","keyFinding":"Researchers developed a new lateral flow test that detects brain natriuretic peptide (BNP) at clinically relevant levels (100 pg/mL threshold) in just 30 minutes at room temperature without requiring enzymes, cold storage, or laboratory equipment. The system uses two aptamers that simultaneously bind BNP, triggering an enzyme-free DNA amplification cascade that produces a visual result on a simple test strip.","whyItMatters":"BNP is the key blood biomarker for diagnosing heart failure, but current tests require expensive lab equipment and cold-stored antibodies. A rapid, room-temperature test strip could bring heart failure diagnosis to emergency rooms, ambulances, and clinics in resource-limited settings where lab-based immunoassays aren't available.","specificNumbers":"Clinical rule-out threshold: 100 pg/mL (0.03 nM) · Detection time: 30 minutes · Room temperature operation · Enzyme-free amplification · Dual-aptamer system","methodology":"Proof-of-concept laboratory study developing a lateral flow biosensor. Designed a dual-aptamer system where two DNA aptamers bind BNP simultaneously, releasing complementary DNA strands that trigger cyclic isothermal amplification. The amplified DNA products are detected on a lateral flow test strip providing visual readout. Tested with spiked samples at room temperature.","limitations":"Proof-of-concept stage only — not yet validated with real human blood samples. Performance in clinical settings with complex biological matrices (blood, serum) is unknown. No comparison with existing commercial BNP immunoassays. Manufacturing scalability and cost not addressed. Interference from other blood components needs testing."},{"rthcId":"RPEP-16555","title":"Engineered CGRP Eye Drops Restore Tear Secretion via TRPM8-SSN Circuitry in a Postrefractive Surgery Mouse Model.","authors":"Zhang, Mengyao; Bai, Xiaofei; Li, Xiaoyu; Liu, Mengqi; Fu, Yali; Dou, Shengqian; Qu, Mingli; Wang, Qun; Zhou, Qingjun","year":2026,"journal":"Investigative ophthalmology & visual science, 67(1), 45","doi":"10.1167/iovs.67.1.45","pmid":"41563016","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16556","title":"Nasal-to-brain delivery of CCR5 antagonist for reshaping the dysregulated microglia-neuron axis and enhancing post-traumatic cognitive function.","authors":"Zhang, Pengcheng; Wang, Yaxin; Xu, Yigang; Li, Xueping; Yu, Xuya; Li, Yi; Zhu, Dunwan; Luo, Fang; Li, Wen; Jin, Xu","year":2026,"journal":"Biomaterials, 324, 123479","doi":"10.1016/j.biomaterials.2025.123479","pmid":"40499228","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16557","title":"3D printed scaffolds regulated by neural-bone metabolic coupling promote bone unit regeneration.","authors":"Zhang, Pengrui; Li, Linfeng; Yan, Caiping; Cao, Xinna; Lai, Neng; Lei, Yefei; Jiang, Ke; Yang, Hanfeng; Zhang, Haoshaqiang; Cui, Wenguo; Li, Yuling","year":2026,"journal":"Bioactive materials, 57, 284-304","doi":"10.1016/j.bioactmat.2025.10.031","pmid":"41323200","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16558","title":"Identification and characterization of broad-spectrum cathelicidin family antimicrobial peptides from the pygmy sperm whale Kogia breviceps.","authors":"Zhang, Pingchuan; Ye, Zifan; Dou, Haoran; Li, Shuangyu; Jiao, Xudong; Wang, Yipeng","year":2026,"journal":"Biochemical pharmacology, 245, 117675","doi":"10.1016/j.bcp.2026.117675","pmid":"41506548","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16559","title":"Synergistic effects of Akebia saponin D and Semaglutide on diabetic nephropathy and osteoporosis via the Klotho‑p53 signaling axis.","authors":"Zhang, Qian; Wang, Dan; Jia, Hongxia; Zheng, Zongji; Lin, Liyan; Li, Linna; Wang, Ling; Xue, Yaoming","year":2026,"journal":"International journal of molecular medicine, 57(1)","doi":"10.3892/ijmm.2025.5696","pmid":"41268608","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16560","title":"Discovery of a Novel Dual-Targeting KRASG12D/HDAC Peptide Inhibitor for the Treatment of Pancreatic Cancer.","authors":"Zhang, Qiaoxuan; Geng, Yifei; Chen, Haitao; Ni, Jiaping; Guan, Lixia; Zhai, Dong Qing; Wang, Yuting; Xu, Shengtao; Niu, Miao-Miao; Zheng, Lufeng; Hu, Weiwei","year":2026,"journal":"Journal of medicinal chemistry","doi":"10.1021/acs.jmedchem.5c02435","pmid":"41736662","tags":[],"studyType":"preclinical","evidenceStrength":"low-moderate","keyFinding":"Researchers discovered KH-1, the first peptide inhibitor that simultaneously targets two critical cancer-driving proteins: KRAS G12D (the most common mutation in pancreatic cancer) and HDAC (histone deacetylase, a downstream effector). KH-1 bound both targets with nanomolar affinity — Kd of 11.63 nM for KRAS G12D and 20.17 nM for HDAC2.\n\nIn lab tests, KH-1 inhibited pancreatic cancer cell growth, invasion, and migration, induced cell death (apoptosis), and arrested cells in the G0/G1 phase. In a mouse xenograft model, KH-1 significantly suppressed tumor growth without causing obvious organ toxicity.","whyItMatters":"KRAS G12D is mutated in ~40% of pancreatic cancers and was long considered 'undruggable.' HDAC is a downstream signal that KRAS uses to promote tumor growth. Hitting both targets with a single peptide molecule could be more effective than targeting either alone, and the lack of organ toxicity in mice is encouraging for a disease that has a 5-year survival rate below 13%.","specificNumbers":"KRAS G12D binding: Kd = 11.63 ± 0.71 nM · HDAC2 binding: Kd = 20.17 ± 1.26 nM · Significant tumor growth inhibition in xenograft model · No significant organ toxicity","methodology":"KH-1 was identified through integrated virtual screening combining pharmacophore screening and molecular docking. Binding affinity was confirmed by microscale thermophoresis (MST) assays. Anti-cancer activity was tested in human pancreatic cancer cell lines measuring proliferation, invasion, migration, apoptosis (flow cytometry), and cell cycle arrest. In vivo efficacy was evaluated in a mouse xenograft tumor model, with organ toxicity assessed.","limitations":"Mouse xenograft models don't fully recapitulate human pancreatic cancer biology. No human data exists. The peptide's pharmacokinetics (half-life, bioavailability, metabolism) are not discussed. Pancreatic cancer's dense stroma may limit drug penetration in actual patients. Long-term toxicity is not assessed. Comparison to existing KRAS inhibitors or HDAC inhibitors is not provided."},{"rthcId":"RPEP-16561","title":"Development and Mechanistic Evaluation of Cathepsin B-Activatable Peptide-Drug Conjugate PROTACs for Targeted Protein Degradation in Malignant Tumors: Advancing Precision Protein Degradation Therapeutics in Oncology.","authors":"Zhang, Qingqing; Liu, Yu; Zhang, Jie; Dong, Hengtao; Pan, Xiaoyan; Zhang, Jie","year":2026,"journal":"Small (Weinheim an der Bergstrasse, Germany), 22(4), e06562","doi":"10.1002/smll.202506562","pmid":"41388045","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16562","title":"Successful use of immunoadsorption therapy in advanced dilated cardiomyopathy: A case report.","authors":"Zhang, Rendan; Ning, Lvwen; Liu, Ying; Tan, Zhixiong; Kong, Lu; Quan, Xiaoqing; Chen, Xiehui","year":2026,"journal":"Medicine, 105(2), e47080","doi":"10.1097/MD.0000000000047080","pmid":"41517781","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16563","title":"Cell-penetrating peptide-functionalized biomimetic nanovesicles for efficient cataract treatment via enhanced corneal penetration and lens-mitochondria dual targeting.","authors":"Zhang, Renjie; Li, Wei; Wang, Jiahao; Li, Yijin; Chen, Jiang; Hong, Wenxin; Huang, Huiying; Lin, Quankui","year":2026,"journal":"Bioactive materials, 57, 305-322","doi":"10.1016/j.bioactmat.2025.11.016","pmid":"41323208","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16564","title":"Self-assembled nanonetworks of highly stable gemini surfactant-like peptides: antibacterial mechanisms, self-assembly characteristics, and in vivo anti-infection potential.","authors":"Zhang, Ruoshi; Sun, Jing; Fu, Chendi; Yu, Hao; Wang, Shenao; Jiao, Yihan; Zhang, Licong; Feng, Xingjun","year":2026,"journal":"Journal of nanobiotechnology, 24(1), 96","doi":"10.1186/s12951-026-04053-6","pmid":"41547795","tags":["antimicrobial-peptide","self-assembly","nanotechnology"],"studyType":"animal","evidenceStrength":"moderate","keyFinding":"Researchers designed a new class of antimicrobial peptides inspired by gemini surfactants — twin-headed soap-like molecules. The lead peptide IPr self-assembles into nanoribbon networks through non-covalent forces, which dramatically improves its resistance to enzyme degradation. IPr killed all 10 tested bacterial strains (both Gram-negative and Gram-positive), resisted protease breakdown, and tolerated physiological salt concentrations. It works by disrupting bacterial membranes, triggering a cascade of reactive oxygen species accumulation and ATP leakage. In a mouse peritonitis model, IPr showed excellent biocompatibility and significantly reduced systemic bacterial infection severity.","whyItMatters":"The stability problem is the Achilles' heel of antimicrobial peptides — enzymes in the body break them down before they can work. This study offers a fundamentally different solution: instead of chemically modifying individual peptides, they designed peptides that spontaneously self-assemble into protective nanostructures. The nanonetwork formation shields the peptides from enzymatic attack without requiring unnatural amino acids or cyclization, providing a new design template for stable peptide antibiotics.","specificNumbers":"Active against all 10 tested bacterial strains · Gram-negative + Gram-positive coverage · Protease-resistant · Salt-tolerant · Significant infection reduction in mouse peritonitis · Excellent biocompatibility in vivo","methodology":"The team designed gemini surfactant-like peptide templates and synthesized variants. They tested antibacterial activity against 10 bacterial strains, protease stability, and salt tolerance. Molecular dynamics simulations and structural characterization (nanoribbon/nanonetwork visualization) elucidated the self-assembly mechanism. Mechanism studies measured membrane disruption, ROS accumulation, and ATP leakage. In vivo efficacy was tested in a mouse peritonitis infection model with biocompatibility assessment.","limitations":"Preclinical study with no human data. Only one infection model (peritonitis) was tested in vivo. Specific MIC values and quantitative infection reduction data were not provided in the abstract. The long-term stability of the self-assembled nanonetworks under varying physiological conditions is not discussed. Manufacturing scalability and cost are not addressed."},{"rthcId":"RPEP-16565","title":"Efficacy and safety of semaglutide in non-diabetic adults with overweight or obesity: A meta-analysis of randomized controlled trials.","authors":"Zhang, Shenyue; Niu, Shengbo; An, Shengli; Cai, Xinghai; Lao, Xiangqian","year":2026,"journal":"European journal of pharmacology, 1015, 178587","doi":"10.1016/j.ejphar.2026.178587","pmid":"41580006","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16566","title":"Oxidative stress impairs the expansion of regulatory T cells in active vitiligo via dysregulated CGRP-RAMP1-Gαi3 signaling.","authors":"Zhang, Shi-Jiao; Geng, Meng-Meng; Li, Qian-Wen; Li, Xiao-Hui; Zhou, You; Luo, Long-Fei; Jiang, Shan; Lei, Tie-Chi","year":2026,"journal":"Free radical biology & medicine, 245, 18-29","doi":"10.1016/j.freeradbiomed.2025.12.041","pmid":"41453541","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16567","title":"Sensory neurons drive immune exclusion by stimulating a dense extracellular matrix in the breast cancer tumor microenvironment.","authors":"Zhang, Si-Wei; Wang, Han; Xiao, Yi; Liu, Luo-Tian; Shen, Minhong; Wang, Zhuang; Zhao, Shen; Ding, Xiao-Hong; Wang, Ying; Zhuang, Qing-Yuan; Ni, Jinfei; Shao, Zhi-Ming; Jiang, Yi-Zhou","year":2026,"journal":"Cell, 189(4), 1039-1055.e20","doi":"10.1016/j.cell.2026.01.001","pmid":"41650969","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16568","title":"In Vivo Programmed Assembly of Polymer-Peptide Conjugates to Overcome Multistage Drug Delivery Barriers.","authors":"Zhang, Su-Ling; Yu, Fan-Chen; Guan, Ying-Hua; Liu, Jun-An; Wu, Xiu-Hai; Yang, Zi-Xin; Qiao, Zeng-Ying; Wang, Hao","year":2026,"journal":"ACS nano, 20(7), 6176-6185","doi":"10.1021/acsnano.5c20521","pmid":"41674480","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16569","title":"Identification and validation of quinoa-derived ACE inhibitory peptides via multidimensional molecular descriptor clustering.","authors":"Zhang, Wenyuan; Jiang, Xiaoyu; Wang, Miaomiao; Li, Wenxuan; Zhao, Qingxu; Guan, Hui; Liu, Hui; Sun-Waterhouse, Dongxiao; Li, Dapeng","year":2026,"journal":"Food research international (Ottawa, Ont.), 227, 118300","doi":"10.1016/j.foodres.2025.118300","pmid":"41652705","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16570","title":"Neuropeptide-GPCR Regulation of the Neuroimmune Axis in Neurodegeneration: Mechanisms and Translation.","authors":"Zhang, Xiaoting; Bao, Hongying; Hu, Jiayi; Ren, Wenzhi; He, Zhen; Yu-Taeger, Libo; Wu, Aiguo; Li, Juan","year":2026,"journal":"Bioconjugate chemistry","doi":"10.1021/acs.bioconjchem.5c00637","pmid":"41700028","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16571","title":"Calcitonin gene-related peptide inhibits macrophage migration and differentiation via the GTPase Rap1.","authors":"Zhang, Xiatong; Huang, Xiaoyuan; Zhang, Yulian; Xu, Zekai; Chen, Yi; Sun, Jianwei; Chen, Xinyi; Zhang, Yi; Wu, Wenzhi; Chen, Zhuo","year":2026,"journal":"The Journal of biological chemistry, 302(1), 110949","doi":"10.1016/j.jbc.2025.110949","pmid":"41274509","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16572","title":"Rational Engineering and Biosynthesis of Defensin-Derived Antimicrobial Peptides with Broad-Spectrum and Potent Activity.","authors":"Zhang, Xin; Guo, Ziyu; Zhong, Huimin; Zeng, Fan; Chen, Minghai; Li, Feng; Zhang, Xian-En","year":2026,"journal":"ACS synthetic biology, 15(2), 534-547","doi":"10.1021/acssynbio.5c00630","pmid":"41627075","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16573","title":"Enhanced cellular and transdermal delivery of the modified chromatin using gH625 cell-penetrating peptide.","authors":"Zhang, Xinghan; Liang, Yuxin; Zonta, Francesco; Park, Jeong Hyeon","year":2026,"journal":"Nanomedicine : nanotechnology, biology, and medicine, 71, 102884","doi":"10.1016/j.nano.2025.102884","pmid":"41319904","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16574","title":"Inhaled biomimetic nanoparticles enhance pulmonary delivery of tetrandrine and pirfenidone for the treatment of idiopathic pulmonary fibrosis.","authors":"Zhang, Xinrui; Yu, Ruibing; Duan, Xusheng; Zhang, Tenghan; Cheng, Fanyu; Pan, Shan; Zhou, Dongfang; Zhu, Juhong; Cai, Yue; Sun, Xuanrong","year":2026,"journal":"Acta biomaterialia, 212, 613-623","doi":"10.1016/j.actbio.2025.12.038","pmid":"41423167","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16575","title":"GLP-1 receptor agonist liraglutide facilitates rotator cuff healing by reducing tendon cell inflammation and endoplasmic reticulum stress through the GLP-1R-AMPK/SIRT1 pathway.","authors":"Zhang, Xiong; Chi, Ruimin; Xu, Jingting; Meng, Chen; Wang, Zhenggang; Ruo, Wanjun; Xin, Fei; Xu, Tao; Guo, Fengjing; Wang, Genchun; Ye, Yaping","year":2026,"journal":"International immunopharmacology, 169, 116010","doi":"10.1016/j.intimp.2025.116010","pmid":"41386184","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Liraglutide significantly inhibited IL-1β-induced inflammation in tendon cells in vitro, enhanced tendon cell anabolism (tissue building), and upregulated the AMPK/SIRT1 pathway. Mechanistically, the GLP-1 receptor was found to interact with SIRT1 to prevent tendon cell apoptosis (programmed cell death) and endoplasmic reticulum stress.\n\nIn the in vivo rat rotator cuff injury model, liraglutide effectively promoted tissue regeneration and restored biomechanical strength of the repaired tendon, demonstrating both molecular and functional therapeutic effects.","whyItMatters":"Rotator cuff injuries are extremely common — affecting millions annually — and healing is often poor due to chronic inflammation at the repair site. Finding that an already-approved drug like liraglutide can reduce tendon inflammation and improve healing could open a new off-label application, potentially improving outcomes for the many patients who struggle with rotator cuff recovery.","specificNumbers":"","methodology":"The study used both in vitro and in vivo approaches. In vitro, tendon cells were treated with IL-1β to induce inflammation, then treated with liraglutide to assess effects on inflammation, apoptosis, and endoplasmic reticulum stress. The AMPK/SIRT1 signaling pathway was investigated mechanistically. In vivo, a rat rotator cuff injury model was used to evaluate liraglutide's effects on tissue regeneration and biomechanical strength recovery.","limitations":"This is a preclinical study using cell culture and a rat model. Rat rotator cuff anatomy and healing differ from humans. The study did not test different doses or timing of liraglutide treatment. Long-term durability of the healing effect beyond the study period is unknown. Translation to clinical use would require human trials."},{"rthcId":"RPEP-16576","title":"CXCL12a, an antimicrobial chemokine, contains a C-terminal helical structural fragment that exerts potent antimicrobial activity in largemouth bass (Micropterus salmoides).","authors":"Zhang, Yanqi; Xiang, Yangxi; Hu, Yazhen; Li, Chenghua","year":2026,"journal":"Fish & shellfish immunology, 169, 111075","doi":"10.1016/j.fsi.2025.111075","pmid":"41407081","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16577","title":"Antimicrobial Peptides as Cross-Seeding Modulators at the Neurodegenerative-Infectious Interface.","authors":"Zhang, Yanxian; Tang, Yijing; Wang, Lijin; Zheng, Jie","year":2026,"journal":"Research (Washington, D.C.), 9, 1149","doi":"10.34133/research.1149","pmid":"41743850","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16578","title":"Effect of glucagon-like peptide-1 receptor agonists on heart rate in non-diabetic individuals with overweight or obesity: a systematic review and pairwise and network meta-analysis of randomized controlled trials.","authors":"Zhang, Yiwen; Zhang, Chuying; Gong, Xuyang; Cheng, Panpan; Fu, Hang; Diao, Linqi; Song, Chunhua","year":2026,"journal":"European journal of medical research, 31(1), 318","doi":"10.1186/s40001-026-03933-9","pmid":"41582189","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16579","title":"A synthetic hyperglycemia-sensing gene circuit enhances blood glucose homeostasis in diabetic mice.","authors":"Zhang, Yuan; Deng, Shuai; Zhu, Yanlun; Li, Xu; Deng, Jiani; Wang, Chengdong; Sun, Jianmin; Bao, Feixiang; Tang, Shibing; Ye, Haifeng; Chan, Hon Fai; Zhao, Hui","year":2026,"journal":"Molecular therapy : the journal of the American Society of Gene Therapy","doi":"10.1016/j.ymthe.2025.12.059","pmid":"41485052","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16580","title":"SARS-CoV-2 peptide fragments selectively dysregulate specific immune cell populations via Gaussian curvature targeting.","authors":"Zhang, Yue; Silvestre-Roig, Carlos; Fu, Han; Alimohamadi, Haleh; Mandal, Taraknath; Chen, Jonathan W; Luo, Elizabeth Wei-Chia; Anda, Jaime de; Linard Matos, Anna Lívia; Richter, Mathis; Mennella, Anna; Lee, HongKyu; Chan, Liana C; Wang, Yingrui; Wang, Naixin; Wang, Hongyu; Wang, Xiaohan; Lee, Calvin K; Ghosh, Susmita; Matsui, Tsutomu; Weiss, Thomas M; Guo, Tiannan; Zhang, Maomao; Li, Dapeng; Wolfgang, Matthew C; Hagan, Robert S; Li, Melody M H; Gunzer, Matthias; Sickmann, Albert; Frasca, Loredana; Yeaman, Michael R; Lande, Roberto; Cui, Qiang; Soehnlein, Oliver; Wong, Gerard C L","year":2026,"journal":"Proceedings of the National Academy of Sciences of the United States of America, 123(2), e2521841122","doi":"10.1073/pnas.2521841122","pmid":"41505524","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16581","title":"Pressing Intervention Alleviates Pain in Rats With Myofascial Trigger Points via the TRPV1 Channel in Unmyelinated C-Type Sensory Nerve Fibers.","authors":"Zhang, Yuqiao; Tang, Liya; Lv, Xinyue; Li, Jiangshang; Liu, Fei; Kuang, Xiaoxia; Li, Wu","year":2026,"journal":"Journal of integrative neuroscience, 25(2), 46853","doi":"10.31083/JIN46853","pmid":"41762047","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16582","title":"Mo-Rubbing abdominal improves metabolic homeostasis in type 2 diabetes mellitus mice via a jejunum-specific GLP1-dependent mechanism.","authors":"Zhang, Zhi; Gan, Lizhen; Camille, Carrere; He, Xinyi; Li, Lutao; Chen, Yue; Xu, Hanyue; Hu, Jian; Wei, Qingbo; Liu, Wei; Wu, Yunchuan","year":2026,"journal":"Diabetes, obesity & metabolism","doi":"10.1111/dom.70563","pmid":"41725452","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16583","title":"Intraneural delivery of CBD3A6K-RhB via PEG-PLGA nanoparticles for neuropathic pain therapy.","authors":"Zhang, Zhihao; Li, Hao; Liu, Jiarui; Shen, Nana; Zhu, Zhongze; Qi, Xiaoying; Meng, Ming; Wang, Weijiang; Wu, Futong; Qi, Yunkun; Cao, Yong; Ma, Qingming; Xiang, Hongfei","year":2026,"journal":"Journal of controlled release : official journal of the Controlled Release Society, 392, 114662","doi":"10.1016/j.jconrel.2026.114662","pmid":"41620030","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The CRPPNs (CBD3A6K-RhB-loaded PEG-PLGA nanoparticles) showed uniform morphology, high encapsulation efficiency, and sustained peptide release in vitro. When internalized by dorsal root ganglion (DRG) neurons, they significantly inhibited calcium influx and CGRP release — two key drivers of neuropathic pain signaling.\n\nIn a rat chronic constriction injury (CCI) model of the sciatic nerve, a single intraneural injection of CRPPNs produced potent and long-lasting anti-allodynic (reduced sensitivity to touch) and anti-hyperalgesic (reduced pain response) effects that were superior to the free peptide. The mechanism involved downregulation of CaV2.2 expression in both the dorsal root ganglion and spinal cord. Comprehensive biosafety evaluation confirmed excellent biocompatibility.","whyItMatters":"Chronic neuropathic pain affects millions of people and current treatments — opioids, gabapentin, pregabalin — have significant side effects, limited efficacy, and/or addiction risk. A peptide-based therapy delivered directly to the nerve could provide long-lasting relief from a single injection while avoiding systemic side effects. The non-opioid mechanism (blocking calcium channel interactions rather than opioid receptors) is particularly attractive given the ongoing opioid crisis.","specificNumbers":"","methodology":"Researchers engineered a modified peptide inhibitor (CBD3A6K-RhB) with enhanced binding affinity for the CaV2.2-CRMP2 interaction. The peptide was encapsulated in PEG-PLGA nanoparticles using microfluidic technology. In vitro testing assessed nanoparticle morphology, encapsulation efficiency, release kinetics, neuronal uptake, calcium influx inhibition, and CGRP release in DRG neurons. In vivo efficacy was tested in a rat CCI model of the sciatic nerve, with a single intraneural injection. Biosafety was comprehensively evaluated.","limitations":"This is a preclinical study in rats, and pain models in rodents have historically translated poorly to human clinical outcomes. The intraneural injection route, while effective for targeted delivery, requires precision placement that may be technically challenging in clinical practice. Long-term effects beyond the study period were not reported. Only one pain model (CCI) was tested. The specific duration of pain relief was not detailed in the abstract, and whether repeated injections would be needed is unknown."},{"rthcId":"RPEP-16584","title":"Implications of Glucagon-like Peptide-1 Receptor Agonists on Thyroid Function and Thyroid Nodules: A Drug Target Mendelian Randomization and Cohort Study.","authors":"Zhang, Zhijun; Yang, Jingyun; Gao, Ling","year":2026,"journal":"Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists, 32(1), 60-66","doi":"10.1016/j.eprac.2025.07.013","pmid":"40706753","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16585","title":"Liraglutide Ameliorates Injury-Related Vascular Repair by Activating Autophagy Through Modulation of the PI3K-mTOR Signaling Pathway.","authors":"Zhang, Zongyi; Wu, Guixian; Xu, Chaozhi; Li, Shanqian; Zhang, Yulin; Hu, Yue; Wu, Wanhua; Ding, Hongyu; Liu, Yuling; Huang, Yue; Lu, Wenjun; Zheng, Meimei; Zhang, Yue; Wu, Hongxian; Hu, Lina","year":2026,"journal":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 40(1), e71357","doi":"10.1096/fj.202501740RR","pmid":"41486848","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16586","title":"The effects of GLP-1 receptor agonists on metabolic inflammatory markers in patients with type 2 diabetes mellitus: a systematic review and meta-analysis.","authors":"Zhao, Fang; Wang, Haoshu; Li, Shenguang; Yun, Hezhang; Su, Wenbo","year":2026,"journal":"PeerJ, 14, e20710","doi":"10.7717/peerj.20710","pmid":"41660088","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16587","title":"GLP-1 agonists reduce right ventricular mitochondrial dysfunction by inhibiting the GSK3β-Drp1 signalling in pulmonary hypertension.","authors":"Zhao, Lin; Liu, Yanghong; Ou, Ziwei; Zhao, Xiexiong; Zhang, Wen; Li, Tangzhiming; Sheng, Zhe; Chen, Ye; Luo, Hui","year":2026,"journal":"European journal of medical research, 31(1), 243","doi":"10.1186/s40001-025-03815-6","pmid":"41520117","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16588","title":"Cell selectivity and antimicrobial mechanism of novel BMAP-28 analogues against bacteria and Cronobacter sakazakii.","authors":"Zhao, Mingzhang; Ma, Yue; Li, Tianzhu; Qian, Shanshan; Zhang, Jing; Duan, Xiaolei; Zhang, He; Chen, Xianhui; Neng, Xinyu; Jiang, Zhanmei; Hou, Juncai","year":2026,"journal":"Journal of the science of food and agriculture","doi":"10.1002/jsfa.70513","pmid":"41652794","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16589","title":"The GLP-1-miRNA network: Epigenetic control of obesity and metabolic disorders.","authors":"Zhao, Shihua; Qin, Ping; Wang, Xin; You, Qiang","year":2026,"journal":"Diabetes, obesity & metabolism","doi":"10.1111/dom.70551","pmid":"41757415","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16590","title":"The Welander TIA1 mutation dedifferentiates insulin-producing cells - reversal by a GLP-1 receptor agonist.","authors":"Zhao, Tongjian; Cen, Jing; Wang, Xuan; Yang, Mingyu; Lau, Joey; Tengholm, Anders; Sjöholm, Åke; Welsh, Nils","year":2026,"journal":"The Journal of biological chemistry, 111336","doi":"10.1016/j.jbc.2026.111336","pmid":"41786146","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16591","title":"AI-Based D-Amino Acid Substitution for Optimizing Antimicrobial Peptides to Treat Multidrug-Resistant Bacterial Infection.","authors":"Zhao, Yinuo; Kong, Qingzhou; Gong, Haifan; Li, Lixiang; Fu, Jialu; Wan, Boyao; Wang, Peizhu; Li, Xiaojuan; Wang, Yue; Zhang, Jinghui; Yu, Yanbo; Yang, Xiaoyun; Zuo, Xiuli; Wang, Haina; Li, Yanqing","year":2026,"journal":"Advanced science (Weinheim, Baden-Wurttemberg, Germany), 13(10), e18522","doi":"10.1002/advs.202518522","pmid":"41532671","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Researchers developed ADAPT, an AI-based tool that predicts the functional impact of D-amino acid substitutions in antimicrobial peptides. When integrated into a high-throughput screening pipeline, 80% of the generated peptide variants showed enhanced antibacterial activity. The lead peptide dR2-1 demonstrated exceptional broad-spectrum antimicrobial activity, reduced toxicity, and substantially improved stability compared to the parent peptide. Delivered via an engineered hydrogel, dR2-1 effectively treated skin infections in mice through a membrane-targeting mechanism.","whyItMatters":"A major challenge in developing antimicrobial peptides as drugs is their rapid degradation by enzymes. D-amino acid substitution can solve this but previously required tedious trial-and-error. This AI framework dramatically accelerates the optimization process, potentially transforming how peptide antibiotics are developed to combat the growing crisis of multidrug-resistant infections.","specificNumbers":"80% of AI-designed variants showed enhanced activity · lead peptide dR2-1 · broad-spectrum activity · reduced toxicity · effective in mouse skin infection model","methodology":"The team curated a dataset of D-amino acid-substituted AMPs from published literature, then developed the ADAPT AI prediction tool. They integrated it into a high-throughput screening pipeline, synthesized and tested the predicted peptide variants, characterized the lead candidate's mechanism of action, and validated efficacy in a mouse cutaneous infection model using a hydrogel delivery system.","limitations":"In vivo testing was limited to a cutaneous (skin) infection mouse model; systemic infections and other infection sites were not evaluated. The AI tool was trained on existing literature data, which may introduce biases. Long-term safety and pharmacokinetic profiles of the lead peptide require further study."},{"rthcId":"RPEP-16592","title":"Peptide‑potassium channel interaction law-guided design of Kv1.3 channel-selective peptide immunosuppressants.","authors":"Zhao, Yonghui; Zuo, Zheng; Qin, Chenhu; Chen, Zongyun; Cao, Zhijian; Wu, Yingliang","year":2026,"journal":"International journal of biological macromolecules, 341(Pt 2), 150379","doi":"10.1016/j.ijbiomac.2026.150379","pmid":"41558561","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Starting from scorpion toxin BmKTX as a template, the researchers engineered ADIP-6 (BmKTX-K6D/D19K/D33K) through strategic acidic residue redistribution:\n\n- Selectivity: IC50 of 0.8 ± 0.1 nM against hKv1.3; minimal inhibition of other potassium channels even at 1 μM (>1,000-fold selectivity)\n- Cellular: Significantly suppressed IL-2 production in Jurkat T cells (confirming functional immunosuppression)\n- In vivo: Reduced delayed-type hypersensitivity responses and alleviated disease severity in a rat model of experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis\n\nThe design strategy — negatively charged residue scanning based on peptide-potassium channel interaction principles — provides a general framework for creating selective channel blockers.","whyItMatters":"Current immunosuppressants (like cyclosporine) suppress the entire immune system, increasing infection and cancer risk. The Kv1.3 channel is preferentially expressed on the effector memory T cells that drive autoimmune disease, while other T cell types use a different channel (KCa3.1). Selectively blocking Kv1.3 could suppress autoimmune attacks while preserving overall immune defense. ADIP-6's >1,000-fold selectivity over other channels is a major advance toward this goal, and its efficacy in an MS model demonstrates therapeutic potential.","specificNumbers":"","methodology":"Rational peptide engineering using BmKTX (scorpion toxin) as a template. Acidic residue distribution was modulated based on peptide-potassium channel interaction principles to exploit structural differences between hKv1.3 and other channels. The resulting peptides were synthesized and characterized by electrophysiology for channel selectivity (IC50 determination across multiple potassium channels). Functional immunosuppression was tested by measuring IL-2 production in Jurkat cells. In vivo efficacy was assessed in delayed-type hypersensitivity and rat EAE (experimental autoimmune encephalomyelitis) models.","limitations":"Preclinical study — no human safety or efficacy data. The rat EAE model approximates but doesn't fully replicate human multiple sclerosis. Peptide drugs face challenges with stability, oral bioavailability, and potential immunogenicity that weren't addressed. The selectivity panel, while impressive, may not cover all relevant human potassium channels. Long-term safety of chronic Kv1.3 blockade needs assessment. Manufacturing scalability of the engineered peptide at clinical grade wasn't discussed."},{"rthcId":"RPEP-16593","title":"Novel Therapeutic Approach to Preserving or Reversing Pancreatic Islet Beta Cells in Patients With Type 1 Diabetes: A Bayesian Network Meta-Analysis of Comparative Efficacy.","authors":"Zheng, Chen; Lu, Sibiao; Qiang, Di; Xu, Jiale; Xu, Yingying","year":2026,"journal":"Diabetes/metabolism research and reviews, 42(1), e70120","doi":"10.1002/dmrr.70120","pmid":"41493044","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16594","title":"Semaglutide attenuates Alzheimer's disease model progression by targeting microglial NLRP3 inflammasome-mediated neuroinflammation and ferroptosis.","authors":"Zheng, Mingxiao; Zhang, Qianye; Siebert, Hans-Christian; Loers, Gabriele; Wen, Min; Wang, Qingpeng; Zhang, Ruiyan; Han, Jun; Zhang, Ning","year":2026,"journal":"Experimental neurology, 396, 115537","doi":"10.1016/j.expneurol.2025.115537","pmid":"41173224","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16595","title":"Discovery and Preclinical Evaluation of TPM003: A Novel GLP-1/GIP/Glucagon Triple Hormone Receptor Agonist with Robust Efficacy in Obesity and NASH.","authors":"Zheng, Nan; Tu, Longfang; Xu, Pu; Chen, Rongfang; Lu, Jiang; Dai, Wan; Lin, Yanxia; Ouyang, Jianmei; Qiu, Jinying; Wang, You; Wang, Leiming; Shen, Weijun","year":2026,"journal":"Journal of medicinal chemistry, 69(4), 4984-5001","doi":"10.1021/acs.jmedchem.5c03845","pmid":"41640214","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16596","title":"A novel antimicrobial peptide Anguinin55-72 identified from Anguilla japonica exhibiting protection against Edwardsiella tarda infection.","authors":"Zheng, Wenbin; Chen, Fangyi; Yu, Wenhao; Gao, Tingting; Yan, Ziyuan; Bai, Yuqi; Sun, Hang; Wang, Ke-Jian","year":2026,"journal":"Bioorganic chemistry, 173, 109651","doi":"10.1016/j.bioorg.2026.109651","pmid":"41734689","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16597","title":"Beneficial effect of animal skin-derived bioactive peptides on type 2 diabetes mellitus: A review on preparation, structure-activity relationship, and blood glucose regulation mechanism.","authors":"Zheng, Xiaoshan; Guo, Yongxiang; Sun, Dingyan; Shi, Wenzheng; Lu, Ying","year":2026,"journal":"Food research international (Ottawa, Ont.), 227, 118248","doi":"10.1016/j.foodres.2025.118248","pmid":"41652770","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Animal skin collagen contains a unique Gly-Pro-Y sequence structure that is key to producing highly active blood sugar-lowering peptides. These peptides (ASHP) work through competitive inhibition of α-glucosidase (blocking sugar absorption) and DPP-IV (extending the action of natural incretin hormones like GLP-1). Multi-level blood glucose regulation includes improving insulin resistance as a key mechanism.\n\nAI prediction combined with peptide sequence structural analysis has emerged as a crucial strategy for screening the most active peptides from animal skin hydrolysates. Preparation optimization involves high-temperature collagen extraction followed by physical pretreatment and enzyme-specific hydrolysis.","whyItMatters":"DPP-IV is the enzyme that degrades GLP-1 — the same peptide targeted by blockbuster drugs like semaglutide. Finding natural food-derived peptides that inhibit DPP-IV offers a dietary approach to extending GLP-1 activity. Additionally, upcycling animal skin waste into valuable bioactive peptides addresses both health and sustainability goals simultaneously.","specificNumbers":"","methodology":"Narrative review synthesizing recent research on animal skin-derived hypoglycemic peptides. Covers preparation methods (extraction, hydrolysis), structure-activity relationship analysis, enzyme inhibition mechanisms (α-glucosidase, DPP-IV), and multi-pathway blood glucose regulation. Discusses AI-based peptide screening approaches.","limitations":"This is a review without new experimental data. Most evidence for blood sugar-lowering effects comes from in vitro enzyme inhibition assays and animal studies, with limited human clinical data. The bioavailability of these peptides after oral consumption is not well established — they may be degraded during digestion before reaching therapeutic targets. The Gly-Pro-Y sequence is common in many collagen sources, making it unclear which specific animal skins produce the most active peptides."},{"rthcId":"RPEP-16598","title":"Weight loss from glucagon-like peptide-1 receptor agonists by genetic factors in adults with type 2 diabetes.","authors":"Zheng, Yulu; Guo, Zheng; Jeong, Eugene; Xu, Shuai; Samuels, Jason M; Dawwas, Ghadeer K; Tao, Ran; Srivastava, Gitanjali; Chen, You; Yu, Danxia","year":2026,"journal":"Diabetes research and clinical practice, 231, 113041","doi":"10.1016/j.diabres.2025.113041","pmid":"41349614","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16599","title":"Dual-Anchored Clickable Peptide via SPAAC for Gelatinase-Responsive Antibacterial and Osteogenic Functions on Titanium Implants.","authors":"Zhong, Ru; Zhou, Hang; Ye, Chenyang; Chu, Lei; Wang, Lin; Wang, Yingjun","year":2026,"journal":"Advanced science (Weinheim, Baden-Wurttemberg, Germany), e20154","doi":"10.1002/advs.202520154","pmid":"41486549","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16600","title":"Liraglutide Attenuates Endothelial Dysfunction by Inhibiting Hyperglycemia-Induced Endothelial Cell Senescence Through the LARP7/SIRT1 Pathway.","authors":"Zhong, Weili; Yang, Ying; Wang, Yanru","year":2026,"journal":"Archivum immunologiae et therapiae experimentalis, 74(1)","doi":"10.2478/aite-2026-0006","pmid":"41343751","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16601","title":"Ultrafast synthesis of AgNP-based plasmonic film for multiplexed detection of heart failure biomarkers.","authors":"Zhou, Baomei; Tao, Jinqiu; Hu, Juan; Zhang, Chun-Yang","year":2026,"journal":"Biosensors & bioelectronics, 294, 118204","doi":"10.1016/j.bios.2025.118204","pmid":"41223498","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16602","title":"Mitochondrial-Disrupting Antimicrobial Peptide Nanoparticles as Precise Pyroptosis Inducers for Breast Cancer Immunotherapy.","authors":"Zhou, Biyu; Feng, Nana; Xiao, Jian; Huang, Qingqing; Li, Qiushi; Zhang, Zhanzhan; Liu, Yang","year":2026,"journal":"Advanced healthcare materials, e71003","doi":"10.1002/adhm.71003","pmid":"41769765","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16603","title":"Heterogeneity between VIP and GRP neurons underlies AVP receptor signaling in the mouse suprachiasmatic nucleus.","authors":"Zhou, Huihua; Moriyasu, Daichi; Hsiao, Sui-Wen; Yamaguchi, Yoshiaki; Azuma, Morio; Koshimizu, Taka-Aki; Itoi, Keiichi; Sakimura, Kenji; Schwartz, William J; Okamura, Hitoshi; Hasegawa, Emi; Doi, Masao","year":2026,"journal":"Communications biology","doi":"10.1038/s42003-026-09694-9","pmid":"41680426","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16604","title":"Immune-neural regulatory mechanism of osteoporosis induced by androgen deficiency.","authors":"Zhou, Jing; Li, Shuwen; Yang, Huihui; Ma, Ning","year":2026,"journal":"PeerJ, 14, e20737","doi":"10.7717/peerj.20737","pmid":"41727233","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16605","title":"Temporin-GHa-derived peptides enhance the antibacterial and antibiofilm activities of polymyxin B against Pseudomonas aeruginosa and Escherichia coli.","authors":"Zhou, Jinqi; Wang, Yuhuan; Xue, Zhiju; Hu, Fang; Deng, Wenhuan; Tang, Jingxuan; Chen, Yuran; Wang, Rong; Zhang, Yingxia","year":2026,"journal":"Archives of microbiology, 208(5)","doi":"10.1007/s00203-026-04798-6","pmid":"41724849","tags":[],"studyType":"laboratory","evidenceStrength":"low","keyFinding":"Two frog-derived antimicrobial peptides (Temporin-GHaR and Temporin-GHaK) showed synergistic antibacterial activity when combined with the antibiotic polymyxin B against both Pseudomonas aeruginosa and E. coli, achieving a fractional inhibitory concentration index (FICI) below 0.5 — the threshold for true synergy.\n\nThe combination worked by synergistically disrupting both outer and inner bacterial membranes, inhibited biofilm formation at lower concentrations than either agent alone, and enhanced destruction of mature E. coli biofilms. Critically, the combination did not increase hemolytic toxicity to mouse red blood cells, suggesting a favorable safety profile.","whyItMatters":"Antibiotic resistance is a growing global crisis, and Pseudomonas aeruginosa is one of the most dangerous drug-resistant pathogens. Rather than developing entirely new antibiotics — a slow and expensive process — this study shows that pairing existing antibiotics with antimicrobial peptides can restore and enhance their effectiveness, offering a practical combination strategy.","specificNumbers":"FICI <0.5 (synergistic) · 2 peptides tested · 2 bacteria targeted · Biofilm inhibition at sub-MIC concentrations · No increased hemolysis","methodology":"In vitro laboratory study testing Temporin-GHaR and Temporin-GHaK (derived from frog skin antimicrobial peptides) alone and in combination with polymyxin B against P. aeruginosa and E. coli. Methods included checkerboard assays for synergy (FICI), membrane permeability assays (outer and inner membrane disruption), biofilm formation inhibition tests, mature biofilm disruption assays, and hemolysis testing on murine erythrocytes.","limitations":"This is entirely in vitro — no animal infection models or clinical data. In vivo pharmacokinetics, peptide stability in biological fluids, and potential for resistance development were not assessed. The peptides' activity against a broader panel of clinical isolates remains unknown."},{"rthcId":"RPEP-16606","title":"Effects of Glucagon-Like Peptide-1 Receptor Agonists After Treatment Withdrawal: A Systematic Review and Meta-Analysis.","authors":"Zhou, Lei; Wei, Aiming; Pan, Chongsheng; Zhang, Jing; Hu, Peiqun; Li, Xiaoyi; Zhao, Xinyu; Hu, Yushi; He, Benxiang; Liu, Yunlu; Dan, Ranlin; Xu, Wen; Liang, Xinyue; Pan, Xiongfei; Zhu, Tianmin; Li, Hui; Wang, Yang","year":2026,"journal":"Journal of general internal medicine, 41(3), 807-818","doi":"10.1007/s11606-025-09950-4","pmid":"41249646","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16607","title":"ACE1-targeting peptide Acein ameliorates UV-induced skin damage and aging in vivo and in vitro via downregulation of the pro-aging factor CLEC4G.","authors":"Zhou, Tianxiong; Wang, Yunfan; Wang, Jiaqi; Wu, Yixin; Setrerrahmane, Sarra; Zhang, Ruohui; Sun, Baogang; Zhu, Yanzhi; Xu, Hanmei","year":2026,"journal":"Biochemical pharmacology, 243(Pt 2), 117542","doi":"10.1016/j.bcp.2025.117542","pmid":"41241016","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16608","title":"Association between glucagon-like peptide-1 receptor agonists and risk of dementia in older adults with type 2 diabetes: A target trial emulation.","authors":"Zhou, Ting; Tang, Huilin; Zhang, Bingyu; Zhang, Dazheng; Lu, Yiwen; Li, Lu; Chen, Jiajie; Chen, Yong; Asch, David A; Chen, Yong","year":2026,"journal":"Diabetes, obesity & metabolism, 28(3), 1984-1996","doi":"10.1111/dom.70384","pmid":"41424236","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16609","title":"Combination therapies for metabolic dysfunction-associated steatohepatitis: challenges and opportunities.","authors":"Zhou, Xiao-Dong; Fan, Qiong-Yue; Byrne, Christopher D; Targher, Giovanni; Muthiah, Mark D; Huang, Daniel Q; Chen, Qin-Fen; Noureddin, Mazen; Li, Wenhao; Ratziu, Vlad; Loomba, Rohit; Francque, Sven M; Sanyal, Arun J; Zheng, Ming-Hua","year":2026,"journal":"Gut, 75(4), 815-825","doi":"10.1136/gutjnl-2025-337431","pmid":"41475978","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Combination therapies targeting multiple MASH pathways — including GLP-1RAs with FGF-21 analogues or THR-β agonists, and GLP-1/glucagon dual agonists — show promise for improving both liver pathology and systemic metabolic outcomes beyond what single agents can achieve.","whyItMatters":"MASH affects hundreds of millions worldwide and monotherapy provides only partial benefit. Combination strategies combining systemic metabolic agents (like GLP-1RAs) with liver-directed therapies could finally achieve meaningful fibrosis regression and metabolic improvement together.","specificNumbers":"","methodology":"Narrative review published in Gut integrating current knowledge on multitargeted and combination therapies for MASH, examining mechanistic rationales, emerging clinical evidence, and practical implementation considerations.","limitations":"Most combination strategies are in early-stage clinical trials without long-term efficacy or safety data. The optimal combinations, sequencing, and patient selection criteria remain undefined. Drug-drug interactions and cost considerations for multi-agent regimens were not fully addressed."},{"rthcId":"RPEP-16610","title":"A Comprehensive Review on Non-Natural Amino Acid-based Modifications in Antibacterial Peptides.","authors":"Zhou, Yan; Li, Xinghao; Yang, Ke; Zhu, Yin; Ma, Yunqi","year":2026,"journal":"Mini reviews in medicinal chemistry","doi":"10.2174/0113895575404841251121074713","pmid":"41510715","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Incorporating non-natural amino acids into antimicrobial peptides (AMPs) addresses key limitations that have hindered their clinical development: protease degradation, production challenges, safety concerns, and activity retention. Non-natural amino acids with unique structures and properties can optimize AMP-target interactions, expand functional capabilities, and improve stability against enzymatic breakdown. The review covers how these modifications can enhance antibacterial, antiviral, and anticancer properties of AMPs while overcoming the barriers to large-scale application.","whyItMatters":"Antibiotic resistance is one of the greatest global health threats, and antimicrobial peptides are among the most promising alternatives to conventional antibiotics. However, natural AMPs are quickly broken down by enzymes in the body, limiting their therapeutic use. Non-natural amino acid modifications offer a path to making these peptides more stable, potent, and clinically viable — potentially creating a new generation of drugs to combat resistant bacteria, viruses, and even cancer.","specificNumbers":"AMPs from microbes, plants, and animals · Dual mechanisms: membrane disruption + intracellular targets · Non-natural amino acids improve protease resistance · Expanded functions: antibacterial + antiviral + anticancer","methodology":"Comprehensive narrative review examining published research on the use of non-natural amino acids to modify antimicrobial peptides. The review covers the sources, mechanisms of action, and current limitations of AMPs, then focuses on how non-natural amino acid incorporation addresses these challenges.","limitations":"As a review article, no new experimental data is presented. The abstract discusses general principles without quantifying the degree of improvement from specific non-natural amino acid modifications. The practical challenges of manufacturing peptides with non-natural amino acids at scale — including cost and regulatory considerations — are acknowledged but not deeply explored."},{"rthcId":"RPEP-16611","title":"Development of a Long-Acting and Stapled Dual Amylin and Calcitonin Receptor Agonist as Monotherapy and Combination with GLP-1R Agonists for the Treatment of Obesity.","authors":"Zhou, Yaqi; Xu, Pu; Lu, Jiang; Xu, Shujing; Qiu, Wenting; Ning, Xiao; Xu, Jiean; Zheng, Nan","year":2026,"journal":"Bioconjugate chemistry, 37(1), 169-179","doi":"10.1021/acs.bioconjchem.5c00558","pmid":"41429154","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Researchers designed UDA-6, a long-acting stapled peptide that potently activates both amylin (AMY3R) and calcitonin (CTR) receptors, using a novel on-resin Ugi macrocyclization chemistry based on salmon calcitonin. The stapled design enhanced helical stability and extended the half-life to support once-weekly dosing. In diet-induced obese rats, UDA-6 alone produced substantial weight loss and improved metabolic and liver parameters.\n\nWhen combined with semaglutide or tirzepatide, UDA-6 achieved synergistic effects — up to 41% vehicle-adjusted body weight reduction and near-normalized liver fat profiles. This combination performance significantly exceeded what either drug class achieved alone.","whyItMatters":"The 41% body weight reduction in obese rats represents an extraordinary level of efficacy that, if translatable to humans, would far exceed current obesity treatments. This study demonstrates that combining amylin/calcitonin receptor signaling with GLP-1 pathway activation creates synergistic weight loss — opening a new frontier in multi-peptide obesity therapy. The Ugi macrocyclization platform also solves a major problem with amylin-based peptides: their tendency to aggregate and their short half-lives.","specificNumbers":"41% vehicle-adjusted body weight reduction (combination) · Balanced AMY3R + CTR activation · Once-weekly dosing pharmacokinetics · Near-normalized liver lipids · Synergistic with both semaglutide and tirzepatide","methodology":"UDA-6 was designed using Ugi macrocyclization on a salmon calcitonin template to create a stapled (conformationally constrained) peptide. Receptor activation was measured at AMY3R and CTR. Pharmacokinetics were characterized to determine dosing frequency. Efficacy was tested in diet-induced obese (DIO) rats as monotherapy and in combination with semaglutide or tirzepatide. Endpoints included body weight change, metabolic parameters, and liver lipid profiles.","limitations":"All efficacy data is from rats — weight loss percentages in rodents typically don't directly translate to humans. The combination therapy data, while impressive, needs safety assessment (GI tolerability of triple-pathway stimulation is a major concern). The Ugi macrocyclization is a novel chemistry that requires further manufacturing scale-up validation. No human pharmacokinetic or safety data exists. The 41% weight loss was in combination, not monotherapy."},{"rthcId":"RPEP-16612","title":"Efficacy and Safety of Dipeptidyl Peptidase-4 Inhibitors, Glucagon-Like Peptide-1 Receptor Agonists, and Sodium-Glucose Cotransporter-2 Inhibitors as Adjunctive Therapy to Automated Insulin Delivery System in Type 1 Diabetes: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.","authors":"Zhou, Yongwen; Lei, Mengyun; Lin, Qiongyan; Ni, Ying; Lin, Ziqing; Yang, Daizhi; Wang, Chaofan; Xu, Wen; Yan, Jinhua","year":2026,"journal":"Diabetes technology & therapeutics, 15209156261420209","doi":"10.1177/15209156261420209","pmid":"41640116","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16613","title":"Efficacy and safety of cAMP signalling-biased GLP-1 analogue ecnoglutide monotherapy versus placebo in patients with type 2 diabetes (EECOH-1): a multi-centre, randomised, double-blind, placebo-controlled, phase 3 trial.","authors":"Zhu, Dalong; Wang, Weimin; Tong, Guoyu; Ma, Jianhua; Wen, Binhong; Zheng, Xin; Shi, Bimin; Pang, Shuguang; Wang, Kun; Shi, Xiaoxia; Zhang, Xianghua; Fu, Liujun; Liu, Yang; Lu, Yibing; Huang, Debin; Jiang, Chengxia; Pan, Tianrong; Xue, Haibo; Han, Jie; Ding, Hongcheng; Bing, Shaohui; Jiang, Feifei; Zheng, Qing; Yang, Ming; Guan, Lei; Liu, Xingquan; Ning, Jing; Bu, Yue; Guo, Mengying; Yang, Liu; Guo, Wanjun; Li, Yao; Xu, Susan; Pan, Hai","year":2026,"journal":"Nature communications, 17(1), 1420","doi":"10.1038/s41467-025-68165-7","pmid":"41501026","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16614","title":"Glutathione-activatable bola dendrimers mediate tumor-specific cytosolic siRNA delivery via dynamic thiol-disulfide exchange.","authors":"Zhu, Dandan; Zhu, Huiling; Yu, Yaoyun; Zheng, Junyue; Lin, Xianhui; Cheng, Huimin; Mei, Aoxue; Chen, Ming; Li, Yun; Dong, Haijuan; Zhou, Jiehua; Liu, Juan; Liu, Xiaoxuan","year":2026,"journal":"Biomaterials science, 14(4), 1073-1085","doi":"10.1039/d5bm01643f","pmid":"41582851","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16615","title":"Calcitonin Gene-Related Peptide (CGRP) Levels of Children and Adolescents With Migraine: A Systematic Review and Meta-Analysis of Observational Studies.","authors":"Zhu, Guoliang; Yan, Guifang; Luo, Ying; Luo, Juan","year":2026,"journal":"European journal of pain (London, England), 30(1), e70177","doi":"10.1002/ejp.70177","pmid":"41312882","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16616","title":"Liraglutide in Acute Minor Ischemic Stroke or High-Risk Transient Ischemic Attack With Type 2 Diabetes: The LAMP Randomized Clinical Trial.","authors":"Zhu, Huili; Yang, Bin; Lu, Longyan; Li, Yufeng; Sui, Rubo; Liu, Kewei; Tan, Suling; Wang, Lihua; Qiu, Jianmin; Zhong, Jianbin; Wei, Tongguo; Bei, Yuzhang; Huang, Jianmin; Zhang, Suping; Ji, Yan; Wu, Wenjun; Li, Youjia; Huang, Ying; Chen, Yangkun; Huang, Xiaoyun; Zeng, Guoyong; Zhang, Yusheng; Huang, Lian; Li, Hao; Wang, Xiangbing; Wang, Yongjun; Xu, Anding","year":2026,"journal":"JAMA internal medicine, 186(1), 46-54","doi":"10.1001/jamainternmed.2025.5684","pmid":"41182740","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16617","title":"Development of glucagon-like Peptide-1 lysosomal targeting chimeras for degradation of extracellular and membrane proteins.","authors":"Zhu, Liquan; Liu, Haotian; Zeng, Xin; Liu, Ke; Liu, Xiaozhen; Yang, Zhuotao; Duan, Yuchen; Qian, Da; He, Chaoqi; Meng, Xuli","year":2026,"journal":"European journal of medicinal chemistry, 303, 118473","doi":"10.1016/j.ejmech.2025.118473","pmid":"41401593","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16618","title":"β-defensin 2 enhances antiviral immunity via autophagy regulation during Micropterus salmoides rhabdovirus (MSRV) infection and promotes survival in largemouth bass.","authors":"Zhu, Yong-Fei; Wang, Xue-Ni; Hu, Yi-Fan; Li, Chang-Hong; Chen, Jiong","year":2026,"journal":"Fish & shellfish immunology, 168, 110976","doi":"10.1016/j.fsi.2025.110976","pmid":"41177278","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16619","title":"Investigation of Regulation and Binding Patterns of the Human Cathelicidin Peptide LL-37 in Complexation with Nucleic Acids, and its Impact on Neutrophil Extracellular Traps.","authors":"Zielke, Claudia; Rad, Behzad; Nielsen, Josefine E; Li, Jiaxin; Pimcharoen, Sopida; Sawant, Manasi; Lin, Jennifer S; Thiam, Hawa R; Barron, Annelise E","year":2026,"journal":"bioRxiv : the preprint server for biology","doi":"10.64898/2026.02.09.704888","pmid":"41727055","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16620","title":"Synthesis of nucleobase-functionalized peptides and investigation on their self-assembly properties with mRNA as cargo.","authors":"Zimmer, Jan; Nassauer, Jakob; Hoffmann, Elena; Thiermann, Raphael; Bleul, Regina","year":2026,"journal":"Nanoscale, 18(1), 234-241","doi":"10.1039/d5nr04017e","pmid":"41358556","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16621","title":"Survodutide acts through circumventricular organs in the brain and activates neuronal regions associated with appetite regulation.","authors":"Zimmermann, Tina; Bleymehl, Katherin; Haebel, Peter; Perens, Johanna; Roostalu, Urmas; Hecksher-Sørensen, Jacob; Doerr, Jonas; Jarosch, Sebastian; Lam, Daniel; Klein, Holger; Pekcec, Anton; Chehimi, Samar N; Crist, Richard C; Reiner, Benjamin C; Hayes, Matthew R; Augustin, Robert","year":2026,"journal":"Molecular metabolism, 105, 102326","doi":"10.1016/j.molmet.2026.102326","pmid":"41638399","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16622","title":"Vibrio cholerae serotype impacts pathogenicity.","authors":"Zingl, Franz G; Leitner, Deborah R; Fakoya, Bolutife; Morano, Alexander A; Waldor, Matthew K","year":2026,"journal":"Nature communications, 17(1), 1140","doi":"10.1038/s41467-025-67908-w","pmid":"41554737","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16623","title":"Structure-guided rational design of dual-target CGRP antagonist/5HT1F agonist therapeutics for migraine.","authors":"Zou, Fangxia; Mao, Yutong; Li, Chunmei; Wang, Wenyan; Zhang, Wenjing; Wang, Hongbo; Tian, Jingwei; Zhu, Xiaoyin","year":2026,"journal":"European journal of medicinal chemistry, 302(Pt 3), 118361","doi":"10.1016/j.ejmech.2025.118361","pmid":"41270648","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16624","title":"Defensin proteins AtPDF1.2A and AtPDF1.2C mediate cadmium accumulation and plant growth in Arabidopsis.","authors":"Zou, Xia; Liu, YuxiuXin; Yang, Zhiyuan; Guo, Bao; Li, Xuejiao; He, Dawei; Shu, Tianchu; Zhang, Zhenhua; Luo, Jin-Song","year":2026,"journal":"Plant physiology and biochemistry : PPB, 230, 110795","doi":"10.1016/j.plaphy.2025.110795","pmid":"41308293","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16625","title":"Angiogenesis-facilitating and inflammation-modulating SIS-based patches coupled with functional peptides for abdominal wall repair.","authors":"Zou, Zhenyu; Liu, Yuchen; Zhang, Xueying; Cao, Jinxin; Wei, Pengfei; Huang, Yiqian; Jing, Wei; Zhao, Bo; Wang, Minggang","year":2026,"journal":"Materials today. Bio, 37, 102795","doi":"10.1016/j.mtbio.2026.102795","pmid":"41624528","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16626","title":"Multimodal management of hormonal and oncological progression in PTHrP-secreting pancreatic neuroendocrine tumours.","authors":"Zueva, Alexandra; Loh, Ee Wen; Masuka, Shamiso; Wadsley, Jonathan; Newell-Price, John; Munir, Alia","year":2026,"journal":"Endocrine oncology (Bristol, England), 6(1), e250085","doi":"10.1530/EO-25-0085","pmid":"41704230","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The two cases showed strikingly different outcomes despite similar tumor grades (WHO grade 2; Ki-67: 7% and 8%). Patient 1 (age 55) achieved eight years of stable disease with multimodal therapy including somatostatin analogues, PRRT, and chemotherapy, though she developed bilateral hip osteoarthrosis from prolonged high calcium. Patient 2 (age 34) had refractory hypercalcemia that responded only partially to zoledronate, high-dose denosumab, and maximal somatostatin therapy, and she succumbed to progressive disease. Calcium levels tracked reliably with disease activity in both cases.","whyItMatters":"PTHrP-secreting pancreatic neuroendocrine tumors are extremely rare, and there is no established treatment protocol. These cases provide real-world evidence on how peptide-based therapies like somatostatin analogues and PRRT perform in this context, and introduce the practical concept of using calcium as a readily available tumor marker — which could improve monitoring in similar rare cases.","specificNumbers":"","methodology":"This is a case report of two patients with metastatic, well-differentiated PTHrP-secreting pancreatic neuroendocrine tumors treated at a single center. The authors documented treatment timelines, calcium levels, imaging results, and clinical outcomes across multiple treatment modalities.","limitations":"As a two-patient case report, this provides the lowest level of clinical evidence and cannot establish generalizable treatment guidelines. The contrasting outcomes could reflect numerous unmeasured factors. Treatment decisions were made clinically rather than following a standardized protocol, making it impossible to isolate the effect of any single therapy."},{"rthcId":"RPEP-16627","title":"Head-to-head comparison of tirzepatide and semaglutide for weight loss: A systematic review and meta-analysis.","authors":"Zufry, Hendra; Hariyanto, Timotius Ivan","year":2026,"journal":"Obesity research & clinical practice","doi":"10.1016/j.orcp.2026.02.002","pmid":"41723034","tags":[],"studyType":"meta-analysis","evidenceStrength":"high","keyFinding":"Across 12 studies, tirzepatide produced significantly greater weight loss than semaglutide. Tirzepatide users lost an additional 4.61% body weight (95% CI: -6.03 to -3.20, p<0.00001) and 4.76 kg more (95% CI: -6.09 to -3.42, p<0.00001) than semaglutide users.\n\nTirzepatide users were also significantly more likely to reach key weight loss milestones: 1.52× more likely to lose ≥5%, 2.33× more likely to lose ≥10%, 2.82× more likely to lose ≥15%, and 2.28× more likely to lose ≥20% of body weight. All comparisons were statistically significant.","whyItMatters":"This is the first meta-analysis to directly compare the two most prominent weight loss peptide drugs head-to-head. The consistent advantage of tirzepatide across all weight loss thresholds provides the strongest pooled evidence to date for choosing between these therapies.","specificNumbers":"12 studies · MD -4.61% body weight · MD -4.76 kg · OR 2.82 for ≥15% loss · OR 2.28 for ≥20% loss · p<0.00001 for most comparisons","methodology":"Systematic review and meta-analysis searching Europe PMC, Medline, Scopus, and Cochrane Library for RCTs and observational studies directly comparing tirzepatide and semaglutide for weight loss. Pooled analyses used random-effects models to calculate mean differences and odds ratios with 95% confidence intervals. Heterogeneity was assessed using I² statistics.","limitations":"High heterogeneity (I²=87–97%) across all outcomes suggests substantial variability between studies in populations, doses, and follow-up periods. The inclusion of observational studies alongside RCTs limits causal inference. The analysis did not assess safety profiles, cost-effectiveness, or long-term outcomes beyond the study periods."},{"rthcId":"RPEP-16628","title":"Modulation of the photodynamic activity of a cinnamoyl-coumarin-RGD peptide conjugate via cucurbit[8]uril supramolecular assembly.","authors":"Zúñiga, Benjamín; Rivero-Jerez, Paula S; Pino, Sofia Pérez-Del; Bravo-Cabezas, Francisco; Mura, Francisco; Barrias, Pablo; Acuña-Castillo, Claudio; Faúndez, Mario A; Aspeé, Alexis; Zúñiga-Núñez, Daniel; Fuentealba, Denis","year":2026,"journal":"Journal of photochemistry and photobiology. B, Biology, 276, 113376","doi":"10.1016/j.jphotobiol.2026.113376","pmid":"41643631","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The cinnamoyl-coumarin-RGD peptide conjugate (PS-GG(KG)₃G-RGD) formed a stable 1:1 inclusion complex with cucurbit[8]uril (CB[8]) with a high binding constant of (5.0 ± 0.2) × 10⁶ M⁻¹, remaining stable under acidic conditions relevant to tumor microenvironments. Circular dichroism confirmed a stable beta-sheet conformation with high temperature stability.\n\nCritically, the CB[8] complexation modulated the fluorescence lifetime without significantly altering singlet oxygen generation — meaning the therapeutic light-activated mechanism was preserved. In MCF-7 breast cancer cells, the supramolecular assembly significantly enhanced phototoxicity compared to the conjugate alone, demonstrating that the molecular container approach synergizes with peptide-targeted photosensitizer delivery.","whyItMatters":"Photodynamic therapy is a minimally invasive cancer treatment, but its clinical adoption is limited by drug selectivity and solubility issues. This study demonstrates an elegant solution: using a tumor-targeting peptide (RGD) to direct the photosensitizer to cancer cells, while a supramolecular container enhances its therapeutic properties. This dual-optimization approach could make photodynamic therapy more effective and safer by reducing damage to healthy tissue.","specificNumbers":"","methodology":"The researchers synthesized the PS-GG(KG)₃G-RGD conjugate and characterized it using circular dichroism, photophysical measurements in multiple solvents, mass spectrometry, and Job's plot analysis. Supramolecular complexation with CB[8] was confirmed by binding constant determination via fluorescence titration. Singlet oxygen generation was measured to confirm preserved photodynamic activity. In vitro phototoxicity was assessed in MCF-7 breast cancer cells.","limitations":"Testing was limited to a single breast cancer cell line (MCF-7) in vitro. No animal studies or in vivo testing was performed. The study did not compare the RGD-targeted conjugate to a non-targeted control to quantify the specific contribution of peptide-mediated targeting. Long-term stability and pharmacokinetics of the supramolecular complex in biological systems were not assessed. Light penetration depth limits photodynamic therapy to accessible tumors."},{"rthcId":"RPEP-16629","title":"Semaglutide-Mediated Remodeling of Adipose Tissue in Type 2 Diabetes: Molecular Mechanisms Beyond Glycemic Control.","authors":"Ábel, Tatjana; Csobod Csajbókné, Éva","year":2026,"journal":"International journal of molecular sciences, 27(3)","doi":"10.3390/ijms27031186","pmid":"41683613","tags":[],"studyType":"Narrative Review","evidenceStrength":"Moderate","keyFinding":"Semaglutide does far more to fat tissue than simply shrinking it. This review synthesizes evidence showing the drug fundamentally remodels adipose tissue at the molecular level — shifting it from a pro-inflammatory, lipid-storing state toward one that's more oxidative, insulin-sensitive, and metabolically flexible.\n\nKey effects include: enhanced mitochondrial biogenesis and energy-burning capacity, activation of beige fat programming (converting white fat cells toward brown-fat-like energy expenditure), reduced fat tissue inflammation and immune cell infiltration, improved adipokine signaling, reduced fibrosis and tissue stiffness, and depot-specific effects on visceral versus subcutaneous fat. These changes collectively improve insulin sensitivity and reduce ectopic fat deposition in organs like the liver.","whyItMatters":"Most people think of semaglutide as a weight loss drug that reduces appetite. But this review reveals it's simultaneously remodeling the fat tissue that remains — making it healthier and more functional. This matters because adipose tissue dysfunction (inflammation, fibrosis, poor metabolic function) drives insulin resistance and cardiometabolic disease even in people who aren't severely obese. If semaglutide improves fat quality in addition to reducing fat quantity, it may explain why its health benefits exceed what weight loss alone would predict.","specificNumbers":"Effects on visceral + subcutaneous depots · ↑ Mitochondrial biogenesis · ↑ Beige adipocyte programming · ↓ Adipose inflammation · ↓ ECM fibrosis/stiffness · ↓ Ectopic fat deposition · Improved adipokine profile · ↑ Insulin sensitivity","methodology":"Narrative review synthesizing preclinical (animal model and in vitro) and clinical evidence on semaglutide's molecular and cellular effects on adipose tissue in type 2 diabetes. The review covers multiple mechanisms across different fat depots and metabolic pathways.","limitations":"The authors explicitly note that most of the mechanistic evidence comes from animal models or cell culture, not human adipose tissue studies. Human data integrating molecular profiling, advanced imaging, and longitudinal clinical outcomes are needed. It's also unclear how much of the adipose remodeling is directly mediated by GLP-1 receptor activation on fat cells versus indirect effects of weight loss, improved glucose, and reduced caloric intake."},{"rthcId":"RPEP-16630","title":"Evaluation of Soluble ST2 and Galectin-3 Levels in Patients with Heart Failure.","authors":"Çetin, Mustafa; Tanrıverdi, Zulkif; Demirbağ, Recep; Altıparmak, İbrahim Halil; Biçer Yeşilay, Asuman; Tascanov, Mustafa Begenc; Fedai, Halil; Toprak, Kenan; Koyuncu, İsmail","year":2026,"journal":"Turk Kardiyoloji Dernegi arsivi : Turk Kardiyoloji Derneginin yayin organidir","doi":"10.5543/tkda.2025.44679","pmid":"41562360","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"sST2 and galectin-3 levels showed differences across heart failure subtypes classified by ejection fraction, suggesting potential utility as diagnostic biomarkers for heart failure classification.","whyItMatters":"Heart failure treatment depends on ejection fraction classification, but current diagnosis relies heavily on echocardiography. Simple blood biomarkers could enable faster screening and monitoring.","specificNumbers":"","methodology":"Cross-sectional clinical study comparing sST2 and galectin-3 levels across 4 groups (HFrEF, HFmrEF, HFpEF, and healthy controls), n=41 per group.","limitations":"Relatively small groups (n=41 each); cross-sectional design cannot establish causation or track biomarker changes over time; single-center study."},{"rthcId":"RPEP-16631","title":"Plasma CA125 Levels as a Predictor of Major Adverse Cardiac Events in Patients With Acute Coronary Syndrome: A Six-month Follow-up Study.","authors":"Çolak, Nazlı Dilek; Karabağ, Turgut; Çalışkan, Onuralp; Tezcan, Songül","year":2026,"journal":"Journal of the Saudi Heart Association, 38(1), 6","doi":"10.37616/2212-5043.1478","pmid":"41768302","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Plasma CA125 correlated significantly with hs-cTn (r=0.315) and proBNP (r=0.423) and weakly inversely with LVEF (r=−0.186) in ACS patients.","whyItMatters":"Better risk stratification after heart attacks helps clinicians prioritize aggressive treatment for high-risk patients. CA125 is widely available and inexpensive, making it a practical addition to the biomarker toolkit.","specificNumbers":"","methodology":"Prospective cohort study of 127 ACS patients in a coronary care unit with single-admission CA125 measurement and 6-month follow-up for MACE.","limitations":"Small single-center study with only 127 patients. Single CA125 measurement may miss dynamic changes. The study shows correlation, not causation or independent predictive value."},{"rthcId":"RPEP-16632","title":"Modulating food intake by nasal application of peptides targeting melanocortin 4 receptor and ghrelin receptor systems.","authors":"Özbay, Benginur; Jülke, Eva-Maria; List, Moritz; Nowicki, Marcin; Els-Heindl, Sylvia; Immig, Kerstin; Mörl, Karin; Bechmann, Ingo; Beck-Sickinger, Annette G","year":2026,"journal":"Brain communications, 8(1), fcaf450","doi":"10.1093/braincomms/fcaf450","pmid":"41574088","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16633","title":"Advancing obesity treatments through innovations in the design and manufacturing of therapeutic peptides.","authors":"Østergaard, Søren","year":2026,"journal":"Expert opinion on drug discovery, 21(1), 49-72","doi":"10.1080/17460441.2025.2601113","pmid":"41381216","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"GLP-1-based peptide therapeutics have achieved 15-25% weight loss in obesity treatment, a level previously thought achievable only through bariatric surgery. This breakthrough was driven by two key innovations: fatty acid conjugation technology combined with peptide backbone engineering to enable once-weekly dosing, and the development of unimolecular dual and poly-agonists that activate multiple hormone receptor pathways beyond GLP-1 alone.\n\nThe review highlights that while these second-generation therapies offer excellent efficacy and safety, significant barriers remain in scaling up manufacturing infrastructure to meet global demand for hundreds of millions of potential patients.","whyItMatters":"Obesity affects hundreds of millions of people worldwide and is a leading risk factor for diabetes, cardiovascular disease, and many other conditions. The fact that peptide drugs can now achieve weight loss results comparable to surgery — without going under the knife — represents a paradigm shift in how we treat this condition. Understanding the design innovations behind these drugs helps contextualize the rapid pace of development in this space.","specificNumbers":"","methodology":"This is a narrative review article that synthesizes the current landscape of peptide-based obesity therapeutics. The author examines the evolution from first-generation GLP-1 receptor agonists to second-generation peptides, analyzing the design principles, manufacturing innovations, and clinical outcomes that have driven progress in the field.","limitations":"As a review article, this paper synthesizes existing research rather than presenting new experimental data. The 15-25% weight loss figures represent the best outcomes from clinical trials and may not reflect real-world results across diverse populations. The review focuses primarily on the drug design perspective and does not deeply address long-term safety data, cost-effectiveness, or the psychological and behavioral aspects of obesity treatment."},{"rthcId":"RPEP-16634","title":"Investigation of the therapeutic effects of medicinal leech treatment on lower extremity ischemia-reperfusion injury.","authors":"Ünal, Kübranur; Samur, Başak; Sharif, Annahda; İbrahimkhanli, Leyla; Yumuşak, Nihat","year":2026,"journal":"Journal of complementary & integrative medicine","doi":"10.1515/jcim-2025-0427","pmid":"41607083","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"","whyItMatters":"","specificNumbers":"","methodology":"","limitations":""},{"rthcId":"RPEP-16635","title":"Exploring the Role of Cathelicidin LL-37 and Ceragenins in Wound Healing Processes.","authors":"Łuckiewicz, Milena; Wnorowska, Urszula; Zakrzewska, Magdalena; Błażejczyk, Idalia; Daniluk, Tamara; Kondziołka, Wioleta; Savage, Paul B; Bucki, Robert; Piktel, Ewelina","year":2026,"journal":"European journal of pharmacology, 178727","doi":"10.1016/j.ejphar.2026.178727","pmid":"41791569","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The review establishes that LL-37 and ceragenins contribute to wound healing through multiple complementary mechanisms: strong broad-spectrum antimicrobial activity that prevents wound infection; anti-biofilm properties that address one of the main causes of chronic wound persistence; promotion of cell migration and proliferation essential for tissue closure; and modulation of inflammatory responses to reduce excessive scarring and healing complications.\n\nCeragenins offer specific advantages over the natural LL-37 peptide: they are non-peptide mimics resistant to proteolysis (enzymatic degradation), maintain activity in varying environmental conditions (pH, salt concentration), and retain anti-biofilm activity. Their stability in the protease-rich wound environment — where natural peptides are rapidly degraded — is a critical practical advantage.","whyItMatters":"Chronic wounds (diabetic ulcers, pressure sores, venous leg ulcers) affect an estimated 2.5% of the US population and cost the healthcare system over $25 billion annually. Current treatments are inadequate — antibiotics face resistance, and wound dressings are passive. LL-37 and ceragenins represent a paradigm shift: active wound healing agents that simultaneously fight infection, disrupt biofilm, reduce inflammation, and promote tissue repair. This multi-target approach addresses the complex, interconnected reasons why chronic wounds fail to heal.","specificNumbers":"","methodology":"This is a narrative review synthesizing published research on LL-37 and ceragenins in wound healing contexts, including their antimicrobial activity, interactions with skin cells, effects on wound healing-associated signaling pathways, and anti-inflammatory properties.","limitations":"As a narrative review, the paper does not present new experimental data. Most evidence for ceragenins in wound healing comes from in vitro studies and animal models — clinical trial data in human chronic wounds is limited. The optimal formulation, dosing, and application method for clinical use have not been established. Long-term safety of ceragenins applied to wounds, including potential for delayed wound healing or allergic reactions, requires further study. The review may not comprehensively address potential drawbacks or conflicting findings."},{"rthcId":"RPEP-16636","title":"Pediatric Obesity: Diagnostic and Therapeutic Approaches in the Context of International Guidelines With a Focus on Polish Practice.","authors":"Łuczak, Paweł M; Perediatkiewicz, Jakub; Liszka, Paweł; Puchalski, Konrad; Patrzykąt, Klaudia M; Olejnik-Chlewicka, Klaudia M; Urbański, Wojciech; Zasiadła, Marta; Brodowski, Jakub; Ogórek, Agata","year":2026,"journal":"Cureus, 18(1), e101545","doi":"10.7759/cureus.101545","pmid":"41694933","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"Across guidelines from the AAP, WHO, NICE, and Polish pediatric bodies, GLP-1 receptor agonists — specifically liraglutide and semaglutide — are now recommended as adjunctive pharmacotherapy for carefully selected adolescents with severe obesity and significant comorbidities. Family-based lifestyle intervention remains the cornerstone of care across all frameworks, but the review reveals clinically important differences in diagnostic thresholds, risk stratification approaches, and comorbidity screening recommendations between organizations.","whyItMatters":"Childhood obesity rates continue to rise globally, and GLP-1 receptor agonist peptides represent one of the most promising pharmacological advances for treatment. This review helps clinicians understand where international guidelines agree and differ on when to escalate from lifestyle changes to medications like semaglutide, which is especially important as these peptide therapies become more widely available for adolescent patients.","specificNumbers":"","methodology":"The researchers conducted a narrative review comparing current international and national guidelines for pediatric obesity management. They analyzed recommendations from the American Academy of Pediatrics (AAP), World Health Organization (WHO), UK National Institute for Health and Care Excellence (NICE), and the Polish pediatric position statement, along with other European consensus documents. They also summarized key biological mechanisms relevant to clinical assessment and treatment decisions.","limitations":"As a narrative review rather than a systematic review, the study selection may not be comprehensive. The focus on Polish practice may limit generalizability to other healthcare systems. The review does not include original patient data or meta-analyses of treatment outcomes, so it cannot directly quantify the effectiveness of different approaches."},{"rthcId":"RPEP-16637","title":"Kidney disease and heart failure: recent advances and current challenges: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.","authors":"Lam, Carolyn S P; Bozkurt, Biykem; Cherney, David Z I; Ezekowitz, Justin A; Jardine, Meg J; Khan, Sadiya S; Madero, Magdalena; Sarnak, Mark J; Ter Maaten, Jozine M; Cheung, Michael; King, Jennifer M; Grams, Morgan E; Jadoul, Michel; Bansal, Nisha","year":2028,"journal":"Kidney international","doi":"10.1016/j.kint.2025.10.011","pmid":"41791738","tags":[],"studyType":"","evidenceStrength":"","keyFinding":"The conference identified several key conclusions for managing coexisting heart failure (HF) and chronic kidney disease (CKD):\n\nSGLT2 inhibitors, RAAS inhibitors, finerenone, and GLP-1 receptor agonists all show benefits in patients with both HF and CKD, though evidence in advanced CKD remains limited. Natriuretic peptide biomarkers require careful interpretation in CKD patients, and CKD-specific diagnostic thresholds for HF are needed.\n\nCritically, small declines in kidney function after initiating guideline-directed HF therapies are generally hemodynamic in nature and not associated with poor outcomes — meaning they should not trigger treatment discontinuation. The conference called for more integrated cardio-renal management approaches and clinical trials that include relevant kidney endpoints.","whyItMatters":"Heart failure and kidney disease each affect millions of people, and when they occur together — which is very common — outcomes are dramatically worse. Patients often fall between cardiology and nephrology, receiving suboptimal care for one condition while being treated for the other. This KDIGO consensus highlights that peptide-based therapies like GLP-1 receptor agonists and natriuretic peptide biomarkers are increasingly central to managing these complex patients, and calls for the integrated approach these patients need.","specificNumbers":"","methodology":"This paper summarizes conclusions from a KDIGO (Kidney Disease: Improving Global Outcomes) Controversies Conference held in March 2024. The conference brought together international experts in nephrology, cardiology, and related fields to discuss evidence, identify controversies, and reach consensus on key issues in managing the intersection of kidney disease and heart failure.","limitations":"This is a consensus conference report, not a systematic review or meta-analysis. The conclusions represent expert opinion synthesized from available evidence, which may be limited for some subgroups (particularly advanced CKD). Evidence for newer agents like GLP-1RAs in combined HF-CKD populations is still emerging. The conference format may not capture the full spectrum of debate on controversial topics."}]